WORLD TRADE WT/DS48/R/CAN
18August 1997
ORGANIZATION
(97-3371)
Original: English
ECMeasures Concerning Meat andMeat Products (Hormones)
Complaint byCanada
Report ofthePanel
Thereport ofthePanel onECMeasures Concerning Meat andMeat Products (Hormones) -Complaint
byCanada -isbeing circulated toallMembers, pursuant totheDSU. Thereport isbeing circulated
asanunrestricted document from18August 1997 pursuant totheProcedures fortheCirculation and
Derestriction ofWTO Documents (WT/L/160/Rev.1). Members arereminded thatinaccordance with
theDSU onlyparties tothedispute mayappeal apanel report, anappeal shallbelimited toissues
oflawcovered inthepanel report andlegalinterpretations developed bythepanel, andthatthereshall
benoexpartecommunications withthepanel orAppellate Body concerning matters under consideration
bythepanel orAppellate Body.
NotebytheSecretariat: ThisPanel Report shallbeadopted bytheDispute Settlement Body (DSB) within 60daysafterthedateofitscirculation
unless aparty tothedispute decides toappeal ortheDSBdecides byconsensus nottoadopt thereport. IfthePanel Report isappealed
totheAppellate Body, itshallnotbeconsidered foradoption bytheDSBuntilafterthecompletion oftheappeal. Information onthecurrent
status ofthePanel Report isavailable from theWTO Secretariat.-i-
TABLE OFCONTENTS
I. INTRODUCTION ..........................................1
II. FACTUAL ASPECTS ........................................2
1. Themeasures atissue ...................................2
2. Thesubstances atissue (hormones) ..........................4
3. TheCodex Alimentarius standards ..........................5
(a) Theelaboration ofCodex standards ....................5
(b) Codex standards forfivehormones atissue ...............6
4. History ofevents ......................................8
III. CLAIMS OFTHE PARTIES ...................................11
IV. ARGUMENTS OFTHE PARTIES ...............................13
1. Relationship between GATT andtheSPSAgreement ..............13
2. TheSPSAgreement ....................................14
(a) Article 1.1oftheSPSAgreement ......................21
(b) Article 2.1oftheSPSAgreement ......................22
(c) Article 2.2oftheSPSAgreement ......................25
(d) Article 2.3oftheSPSAgreement ......................28
(e) Article 2.4oftheSPSAgreement ......................30
(f) Article 3.1oftheSPSAgreement ......................31
(g) Article 3.3oftheSPSAgreement ......................35
(h) Article 5oftheSPSAgreement .......................42
(i) Articles 5.1and5.2oftheSPSAgreement ................48
(i) Thenature andmode ofaction ofhormones ..........58
(ii) Metabolites ...............................67
(iii) Combinations ofhormones andmultiple exposure ......69
(iv) Detection andControl ........................72
(v) Administration anduseofhormones ...............73
(vi) Other parameters ...........................80
(vii) Theprecautionary principle .....................80
(viii) Animal health protection .......................82
(j) Article 5.4.....................................84
(k) Article 5.5.....................................84
(l) Article 5.6oftheSPSAgreement ......................112
3. Agreement onTechnical Barriers toTrade .....................113
4. GATT .............................................115
(a) Article III.....................................115
(b) Article XI.....................................124
(c) Article XX.....................................124
5. Nullification andimpairment ..............................124
V. THIRD PARTIES SUBMISSIONS ................................128
1. Australia .......................................128
2. Norway ............................................131
3. NewZealand ........................................133
4. United States ........................................135
VI. PANEL 'SCONSULTATION WITH SCIENTIFIC EXPERTS ..............140
Panel procedures withregard toscientific expertise ....................141
Views ofthescientific experts ..................................142-ii-
VII. INTERIM REVIEW .........................................187
VIII. FINDINGS ...............................................190
A. CLAIMS OFTHE PARTIES ..................................190
B. ORGANIZATIONAL ISSUES ..................................191
1. Scientific evidence .....................................191
2. Third party rights .....................................193
C. GENERAL INTERPRETATIVE ISSUES ..........................195
1. Scope ofthemeasures indispute ...........................195
2. Application oftheSPSAgreement, theTBT Agreement andGATT ....196
3. Relationship between theSPSAgreement andGATT ..............198
D. THE SPSAGREEMENT .....................................201
1. Overview oftheprovisions indispute ........................201
2. Burden ofproof ......................................201
3. Article 3.1: sanitary measures based oninternational standards ......203
(a) Codex standards .................................203
(b) Sanitary measures based onCodex standards ..............207
(i) Themeaning ofbased on......................207
(ii) Comparison oflevels ofsanitary protection ..........208
4. Article 3.3: sanitary measures notbased oninternational standards ....209
(a) Requirements forjustification ........................210
(b) Burden ofproof .................................211
5. Article 5:"Assessment ofRiskandDetermination oftheAppropriate Level
ofSanitary orPhytosanitary Protection" ......................212
(a) Riskassessment andriskmanagement ...................212
(b) Articles 5.1to5.3: riskassessment ....................214
(i) Techniques andfactors tobetaken intoaccount .......215
(ii) Theexistence ofariskassessment ................216
(iii) Sanitary measures tobebased onariskassessment .....218
(c) Articles 5.4to5.6: riskmanagement ...................231
(i) Article 5.4: minimizing trade effects ...............232
(ii) Article 5.5: distinctions inlevels ofprotection ........233
(iii) Article 5.6:measures notmore trade restrictive than
required toachieve theappropriate levelofprotection ...250
(d) Article 5.7: provisional sanitary measures ...............251
6. Sanitary measures where nointernational standards exist: melengestrol
acetate ("MGA") .....................................251
(a) Burden ofproof .................................252
(b) Articles 5.1to5.3: riskassessment ....................252
(c) Article 5.5: distinctions inlevels ofprotection .............254
(i) MGA forgrowth promotion compared tothenatural
hormones occurring endogenously inmeat andother
foods ..................................254
(ii) MGA forgrowth promotion compared tocarbadox and
olaquindox .............................255
7. Article 2:"Basic Rights andObligations" .....................256
E. ARTICLES IIIAND XIOFGATT ..............................256-iii-
F. CLAIMOFNULLIFICATIONANDIMPAIRMENTUNDERARTICLEXXIII:1(b)
OFGATT ...............................................256
G. CONCLUDING REMARKS ...................................256
IX. CONCLUSIONS ...........................................257
ANNEX ......................................................259WT/DS48/R/CAN
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I. INTRODUCTION
1.1 On28June1996, Canada requested consultations withtheEuropean Communities pursuant
toArticle 4oftheUnderstanding onRules andProcedures Governing theSettlement ofDisputes
("DSU"), Article 11oftheAgreement ontheApplication ofSanitary andPhytosanitary Measures
("SPS Agreement"), Article 14oftheAgreement onTechnical Barriers toTrade ("TBT Agreement"),
Article 19oftheAgreement onAgriculture, andArticle XXII oftheGeneral Agreement onTariffs
andTrade 1994("GATT"), regarding theCouncil Directive Prohibiting theUseinLivestock Farming
ofCertain Substances Having aHormonal Action andrelated measures which "...adversely affect
theimportation oflivestock andmeatfrom livestock" (WT/DS48/1) .
1.2 Pursuant toArticle 4.11oftheDSU, Australia requested tobejoined inthese consultations
on16July1997(WT/DS48/2), theUnited States on17July(WT/DS48/3) andNewZealand on18July
(WT/DS48/4). TheEuropean Communities denied therequest oftheUnited States tojoinconsultations.
On25July1996, Canada, Australia, andNewZealand heldjointconsultations withtheEuropean
Communities butfailed toreach amutually satisfactory solution.
1.3 On27September 1996, pursuant toArticle XXIII oftheGeneral Agreement onTariffs and
Trade 1994, Article 11oftheAgreement ontheApplication ofSanitary andPhytosanitary Measures,
Article 14oftheAgreement onTechnical Barriers toTrade, Article 19oftheAgreement onAgriculture
andArticles 4and6oftheDSU, Canada requested theDispute Settlement Body ("DSB") toestablish
apanel withstandard terms ofreference (WT/DS48/5). Canada claimed that:
"(a) theECmeasures areinconsistent with:
(i) theAgreement ontheApplication ofSanitary andPhytosanitary Measures,
andinparticular Articles 2,3and5thereof;
(ii) theGeneral Agreement onTariffs andTrade 1994, andinparticular Articles III
orXIthereof;
(iii) theAgreement onTechnical Barriers toTrade, andinparticular Articles 2
and5thereof;
(iv) theAgreement onAgriculture, andinparticular Article 4thereof; and
"(b) theapplication oftheECmeasures otherwise nullifies orimpairs thebenefits accruing
toCanada pursuant totheAgreement Establishing theWorld Trade Organization."
1.4 On16October 1996, theDSBestablished apanel inaccordance withtherequest made by
Canada. Theagreed terms ofreference ofthePanel were (WT/DS48/6):
"Toexamine, inthelightoftherelevant provisions ofthecovered agreements citedbyCanada
indocument WT/DS48/5, thematter referred totheDSBbyCanada inthatdocument andto
make suchfindings aswillassist theDSBinmaking therecommendations oringiving the
rulings provided forinthose agreements".
1.5 Australia, NewZealand, Norway andtheUnited States reserved theirrighttoparticipate in
thePanel proceedings asthirdparties, andallpresented arguments tothePanel.WT/DS48/R/CAN
Page2
1.6 Theparties tothedispute agreed on4November 1996 tothefollowing composition ofthe
Panel:
Chairman: Mr.Thomas Cottier
Members: Mr.Peter Palecka
Mr.JunYokota
1.7 ThePanel metwiththeparties on7January 1997 and19February 1997. Itmetwiththird
parties on7January 1997. ThePanel consulted with scientific andtechnical experts on17-
18February 1997, jointly withtheparties tothisdispute andtheparties tothedispute US-EC Measures
Concerning Meat andMeat Products (Hormones).1
1.8 ThePanel issued itsinterim report totheparties on7May1997. Following arequest made
bytheEuropean Communities pursuant toArticle 15.2oftheDSU, thePanel heldafurther meeting
withtheParties on4June1997. ThePanel issued itsfinalreport totheParties tothedispute on
30June1997.
II. FACTUAL ASPECTS
1. Themeasures atissue
2.1 This dispute concerns ECmeasures, inparticular Council Directive 81/602/EEC
("Directive 81/602/EEC"), Council Directive 88/146/EEC ("Directive 88/146/EEC") andCouncil
Directive 88/299/EEC ("Directive 88/299/EEC").2
2.2 Directive 81/602/EEC prohibits theadministering tofarm animals ofsubstances having a
thyrostatic action orsubstances having anoestrogenic, androgenic orgestagenic action; theplacing
onthemarket orslaughtering offarmanimals towhich these substances havebeenadministered; the
placing onthemarket ofmeatfromsuchanimals; theprocessing ofmeatfromsuchanimals andthe
placing onthemarket ofmeat products prepared from orwithsuchmeat. TheDirective provides
twoexceptions totheprohibition: oneexception isprovided forsubstances withanoestrogenic,
androgenic orgestagenic action when theyareusedfortherapeutic purposes andadministered bya
veterinarian. Theother exception wasprovided forfivegrowth promoting hormones -oestradiol-17 ,
progesterone, testosterone, trenbolone acetate andzeranol -when theywereusedforgrowth promotion
purposes andtheirusewasgoverned according totheindividual regulatory schemes maintained by
member States. Thisexception wasmade pending anexamination oftheeffects ofthese hormones
onthehealth ofconsumers andtheadoption ofanECrule. Member States areobliged toapply their
regulatory schemes toimports fromthirdcountries inamanner notmore favourable thanthatapplied
tointra-EC trade.
2.3 Directive 88/146/EEC extends theprohibition imposed byDirective 81/602/EEC tothe
administration tofarmanimals oftrenbolone acetate andzeranol foranypurpose, andoestradiol-17 ,
testosterone andprogesterone forfattening purposes. However, theDirective maintains thepermission
toadminister these threenatural hormones toanimals fortherapeutic andzootechnical purposes under
prescribed conditions; inparticular, therapeutic treatment isdefined tomean theadministering toan
1WT/DS26/7.
2OthermeasuresrelevanttothedisputearecontainedinDirectives72/462/EEC,81/851/EEC,81/852/EEC,85/358/EEC,
referencedinDirective88/146/EEC;thedecisions,controlprogrammeandderogationsreferredtoinArticle6(2),Article6(7)
andArticle 7,respectively, ofDirective 88/146/EEC; andanyamendments ormodifications, including Directives 96/22/EC
and96/23/EC.WT/DS48/R/CAN
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individual animal ofanyofthesubstances which areauthorized totreatafertility problem diagnosed
onexamination byaveterinarian. Theproducts which areusedfortherapeutic treatment mayby
administered onlybyaveterinarian, intheform ofaninjection (totheexclusion ofimplantation) to
farmanimals which havebeenclearly identified. Suchtreatment mustberegistered bytheveterinarian
andthese animals maynotbeslaughtered before expiry oftheperiod fixed. Inthecaseofanimals
attheendoftheirreproductive career, thetreatments areprohibited from being administered during
thefattening period following theendoftheirbreeding life. Theimportation from third countries
ofanimals andmeat from animals towhich have been administered substances withthyrostatic,
oestrogenic,androgenicorgestagenicactionisprohibited.3However,undercertainconditions,Article7
ofDirective 88/146/EEC allows trade inthose animals andmeat from those animals treated for
therapeutic orzootechnical purposes, including imports from third countries.4Article 4of
Directive 88/146/EEC explicitly requires thatundertakings intheECmember States producing the
prohibited hormones, those companies authorized tomarket these hormones forwhatever purposes
andundertakings producing pharmaceutical andveterinary products based onthose substances, must
keepadetailed register recording (inchronological order) thequantities produced oracquired andthose
soldorusedfortheproduction ofpharmaceutical andveterinary products.
2.4 Directive 88/299/EEC laysdown theconditions forapplying thederogations, provided for
inArticle 7ofDirective 88/146/EEC, from theprohibition ontrade incertain categories ofanimals
andtheirmeat. Thefirstderogation oftheDirective requires member States toauthorize tradeinanimals
intended forreproduction andreproductive animals attheendoftheircareer (andofmeat ofsuch
animals) which, during theirreproductive career, haveundergone oneoftwocategories oftreatments.
Thefirstcategory istherapeutic treatment withoneofthefollowing substances: oestradiol-17 ,
testosterone andprogesterone; andthose derivatives which readily yield theparent compound on
hydrolysis afterabsorption atthesiteofapplication which appear inalistofapproved products. The
second category istheadministration ofsubstances having anoestrogenic, androgenic orgestagenic
action forsynchronization ofoestrus, termination ofunwanted gestation, theimprovement offertility
andthepreparation ofdonors andrecipients fortheimplantation ofembryos, provided thattheproducts
inwhich theyarecontained appear onalistofapproved products andwiththerespect ofstrictconditions
ofuseconcerning, inparticular, therespect ofthewithdrawal period, themonitoring ofthose conditions
ofuseandofthemeans ofidentification oftheanimals. Inaddition, Articles 3and4ofthisDirective
provide thattrade between themember States oftheEuropean Communities inanimals intended for
reproduction andreproductive animals andmeatfromsuchanimals isallowed onlyifalltheconditions
laiddown intheDirective arerespected, inparticular asregards thewaiting period andtherequirement
thatanimals havenotreceived anyoftheabove treatments withanyoftheabove substances during
thefattening period following theendoftheirbreeding life.TheECstamp maybeaffixed tothemeat
only ifthewaiting time ended before theanimals areslaughtered. Thesecond derogation in
3Article 6(7)ofDirective 88/146/EEC requires theestablishment ofacontrol programme asregards imports from third
countries toensure thatimports donotreceive more favourable treatment thanECproducts. Thiscontrol programme also
provides forrulesonthefrequency ofcontrols onimports fromeachthirdcountry andonguarantees offered bytheinspection
regulation ofthird countries. Such checks onimports arenowcarried outinaccordance withDirectives 91/496/EEC and
90/675/EEC.
4Article 7ofDirective 88/146/EEC allows derogations inrespect totrade inanimals intended forreproduction and
reproductive animals attheendoftheircareer (andinrespect ofmeat from these various animals, taking intoaccount the
guarantees given), which inthecourse oftheir existence have been treated under theprovisions ofArticle 4of
Directive 81/602/EEC. Thisarticle authorizes theadministration tofarmanimals ofsubstances withoestrogenic, androgenic
orgestagenic action approved inaccordance withtheDirectives onveterinary medical products (other thansubstances referred
toinArticle 3ofDirective 81/602/EEC) fortherapeutic use,synchronization ofoestrus, termination ofunwanted gestation,
theimprovement offertility andthepreparation ofdonors andrecipients fortheimplantation ofembryos. Theadministering
ofthese substances shallbeeffected byaveterinarian, however, member States mayallow thesynchronization ofoestrus
andthepreparation ofdonors andrecipients fortheimplantation ofembryos tobedone notbyaveterinarian butunder his
direct responsibility.WT/DS48/R/CAN
Page4
Directive 88/299/EEC allows imports fromthirdcountries oftreated animals andmeatofsuchanimals
under guarantees equivalent tothose fordomestic animals andmeat.
2.5 Directive 96/22/EC willreplace Directives 81/602/EEC, 88/146/EEC and88/299/EEC asfrom
1July1997. Itwillmaintain theprohibition ontheuseofthese hormones forgrowth promotion
purposes; extend theprohibition ontheuseofbeta-agonists; restrict theuseofthehormones atissue
fortherapeutic orzootechnical purposes, reinforcing inparticular theroleoftheveterinarian; and
reinforce theprovisions oncontrol andtesting. Penalties andsanctions incaseofviolations areto
beincreased where checks detect thepresence ofprohibited substances orproducts orresidues of
substances administered illegally. Such substances orproducts willbeconfiscated andanytreated
animals ormeatplaced under official supervision untilpenalties havebeenapplied.
2. Thesubstances atissue (hormones)
2.6 Hormones (chemicals) produced bythebodies ofhumans andanimals arecalled endogenous
ornatural hormones. Compounds chemically synthesized tomimic theeffect ofnatural hormones
arecalled synthetic orxenobiotic hormones (phyto-hormones areproduced bysome plants.) Natural
hormones aresecreted intotheblood stream byspecialized cellsandtravel throughout thebody.
Hormones actbybinding protein receptors present inhormone-responsive tissues. Thereceptor
undergoes aconformational change, binds tospecific DNA sequences andregulates specific genes within
acell.Synthetic hormones maydiffer fromendogenous (natural) hormones intheirrateofmetabolism
andexcretion.
2.7 Hormones function infourbroad areas: reproduction; growth anddevelopment; maintenance
oftheinternal environment; andproduction, utilization andstorage ofenergy. Onehormone can
havemultiple actions. Forexample, themale hormone testosterone controls many processes from
thedevelopment ofthefetus tolibido intheadult. Onefunction maybecontrolled bymultiple
hormones: themenstrual cycle involves oestradiol, progesterone, follicle-stimulating hormone and
luteinizing hormone.
2.8 Ofthesixhormones involved inthisdispute, threearenaturally occurring hormones produced
byhumans andanimals: oestradiol-17 ,progesterone andtestosterone (hereafter alsoreferred toas
natural hormones). Oestradiol-17 isasexsteroidal hormone withoestrogenic action (i.e.,responsible
forfemale characteristics); testosterone isasexsteroidal hormone withandrogenic action (i.e.,
responsible formalecharacteristics); progesterone isasexsteroidal hormone withgestagenic action
(i.e.,responsibleformaintainingpregnancy).Thesethreehormonesareproducedthroughoutthelifetime
ofeachindividual andarerequired fornormal physiological functioning andmaturation. Hormone
levels varywiththetissue, withthespecies ofanimal andwiththesexandindividual. Hormone levels
varymost dramatically withpuberty, pregnancy andcastration.
2.9 Theotherthreehormonesinvolvedinthisdisputeareartificiallyproducedhormones:trenbolone,
zeranol andmelengestrol acetate (MGA) (hereafter alsoreferred toassynthetic hormones). These
hormones mimic thebiological activity ofthenatural hormones. Trenbolone mimics theaction of
testosterone; zeranol mimics theaction ofoestradiol-17 ;andMGA mimics progesterone.
2.10 InCanada, thethree natural hormones maybeadministered toanimals tocorrect certain
endocrine disfunctions (hereafter "therapeutic" purposes); oestradiol-17 andprogesterone maybe
administered forbreeding purposes suchassynchronizing oestrus andpreparing female animals for
artificial insemination (hereafter "zootechnical" purposes); allsixsubstances atissueareusedtoincrease
thefeedefficiency andtherateofanimal growth (hereafter "growth promotion" purposes). Fiveof
thesehormones (except MGA) areformulated aspellets (withapproved andfixedamounts ofcompound)
designed tobeimplanted intheearoftheanimal. Theearisdiscarded atslaughter. MGA is
administered asafeedadditive.WT/DS48/R/CAN
Page5
3. TheCodex Alimentarius standards
2.11 TheSPSAgreement makes reference, inanumber ofprovisions, to"therelevant international
standards, guidelines andrecommendations". Annex A:3(a) oftheSPSAgreement states thatthe
international standards, guidelines andrecommendations relevant forfoodsafety arethose established
bytheCodexAlimentariusCommissionrelatingtofoodadditives,veterinarydrugandpesticideresidues,
contaminants, methods ofanalysis andsampling, andcodes andguidelines ofhygienic practice.
2.12 TheCodex Alimentarius Commission ("Codex Commission") isajointFAO/WHO advisory
bodyestablished toimplement theJointFAO/WHO Food Standards Programme. Thepurpose ofthis
programme istoprotect thehealth ofconsumers andtoensure fairpractices infoodtrade through
theelaborationoffoodstandards.Thesestandards,togetherwithnotificationsreceivedfromgovernments
withrespect totheiracceptance orotherwise ofthestandards, constitute theCodex Alimentarius. The
Codex Alimentarius ("Codex") isthusacollection ofinternationally adopted foodstandards presented
inauniform manner.
2.13 Membership oftheCodex Commission isopentoallmember Nations andAssociate members
ofFAO and/or WHO andiscomposed ofgovernment representatives ofthese members. Most ofits
members, including Canada andtheECmember States, areWTO Members. TheEuropean Community
hasanobserver status intheCodex Commission. TheCodex Commission hasestablished anumber
ofsubsidiary bodies, including theCodex Committee onResidues ofVeterinary Drugs inFood
("CCRVDF").
2.14 Thetechnicalandscientificanalysisofveterinarydrugs,foodadditivesandsomeothersubstances
infoods andbeverages isnotundertaken bytheCodex Commission itself butindependently bythe
Joint FAO/WHO Expert Committee onFood Additives ("JECFA"). TheJECFA iscomposed of
independent scientists whoserve intheirindividual capacities asexperts, notasrepresentatives oftheir
governments ororganizations. ThegoaloftheJECFA evaluation ofveterinary drugs is:
"toestablish safelevels ofintake bysetting Acceptable Daily Intakes (ADI) andtodevelop
maximum residue limits when veterinary drugs areusedinaccordance withgood veterinary
practice"5.
(a) Theelaboration ofCodex standards
2.15 Theelaboration ofCodex standards involves an8-step process:
Step1:TheCodex Commission decides toelaborate astandard andidentifies which subsidiary
body orother body should undertake thework, taking intoaccount the"Criteria forthe
Establishment ofWork Priorities andfortheEstablishment ofSubsidiary Bodies". Decisions
toelaborate standards mayalsobetaken bysubsidiary bodies oftheCodex Commission subject
tosubsequent approval bytheCodex Commission oritsExecutive Committee.
Step2:TheCodex Commission secretariat arranges forthepreparation ofa"proposed draft
standard". Inthecaseofveterinary drugs, JECFA isincharge ofpreparing recommendations
formaximum residue levels.
Step3:Thesecretariat distributes the"proposed draft standard" tothemembers ofthe
Commission forcomments.
5Codex Alimentarius, Vol.3, Residues ofVeterinary Drugs inFoods, p.vi.WT/DS48/R/CAN
Page6
Step4:Thecomments received aresentbythesecretariat totheCCRVDF which considers
thecomments and,ifappropriate, amends theproposed draftstandard.
Step5:Theproposed draft standard issubmitted through thesecretariat totheCodex
Commission ortotheExecutive Committee withaviewtoitsadoption asa"draft standard".
Step6:The"draft standard" issentbythesecretariat toallmembers andinterested international
organizationsforcommentsonallaspects,includingpossibleimplicationsofthe"draftstandard"
fortheireconomic interests.
Step7:Thecomments received aresentbythesecretariat totheCCVDRF, which hasthe
power toconsider suchcomments andamend the"draft standard".
Step8:The"draft standard" issubmitted through thesecretariat totheCommission together
withanywritten proposals received frommembers andinterested international organizations
foramendments atStep8withaview toitsadoption asa"Codex standard". Adoption of
standards isnormally doneonthebasisofaconsensus decision, however, ifrequested, avote
maybetaken. Inthiscase, adecision bythemajority ofCodex members isrequired. An
accelerated elaboration procedure maybeusedwhen there isanurgent needforastandard.
2.16 TheCodexCommissionkeepsunderreviewandmayreviseCodexstandards,generallyfollowing
procedures similar tothose usedfortheelaboration ofstandards. Codex standards arepublished and
senttogovernments foracceptance andtointernational organizations towhich competence inthematter
hasbeentransferred bytheirmember States. Acceptance ofthestandards isvoluntary andCodex
members arenotrequired toindicate formal acceptance ofCodex standards, guidelines or
recommendations. Theimplementation ofCodex standards atthenational levelistheresponsibility
ofmembers.
(b) Codex standards forfivehormones atissue
2.17 Codex standards forveterinary drugs arenormally stated interms ofanAcceptable Daily Intake
("ADI") andaMaximum Residue Limit ("MRL"). AnADIis"anestimate byJECFA oftheamount
ofaveterinary drug, expressed onabodyweight basis, thatcanbeingested dailyoveralifetime without
appreciable health risk(standard man=60kg)".6AnADIisderived from theexperimental No
Observable Effect Level ("NOEL") inthemostappropriate animal species, byapplying anappropriate
safety factor. Toaccount forsensitivity variabilities between humans andanimals, anddietary
variabilities among humans, asafety factor istypically applied. When datafrom long-term animal
toxicity studies areavailable, asafety factor of100isgenerally applied. Larger safety factors, up
to1000, maybeusedincertain cases.
2.18 ACodex MRL isoneofthetools forensuring thatintake doesnotexceed theADIandthat
"Good Practice intheuseofVeterinary Drugs" ("GPVD") isobserved. Itisthemaximum concentration
ofresidue resulting fromtheuseofaveterinary drug(expressed inµg/kg orµg/kg onafresh weight
basis) thatisrecommended bytheCodex Commission tobelegally permitted orrecognized asacceptable
inoronafood. Testanimals arefirsttreated withthedruginaccordance withproposed GPVD and,
onthebasisofthisusage, tentative MRLs aresetforvarious tissues. These MRLs arethencompared
withtheADI, considering dietary foodintake. IftheMRL established onthebasisofproposed GPVD
would cause theADItobeexceeded, theMRL willbelowered toalevelwhich ensures thattheADI
isnotexceeded, andtheproposed GPVD willalsobemade stricter. If,ontheother hand, theproposed
MRL would notcause theADItobeexceeded (asismostfrequently thecase), theMRL willbeproposed
6Ibid.,p.65.WT/DS48/R/CAN
Page7
foradoption. Thus, MRLs arefrequently setatlevels below (even farbelow) thetheoretical safelevels
determined fromanADI. AnMRL mayalsobereduced tobeconsistent withtheGPVD asapproved
bynational authorities orincreased (toalevelstillbelow thesafelevel) tobedetectable using practical
methods.
2.19 "Good Practice intheUseofVeterinary Drugs" (GPVD), isdefined as:
"theofficial recommended orauthorized usage including withdrawal periods, approved by
national authorities, ofveterinary drugs under practical conditions."7
According totheCodex Commission secretariat, theterms "good veterinary practice" and"good
veterinary andhusbandry practice", when usedinJECFA reports, aresynonyms forGPVD.
2.20 Forthehormones atissue, JECFA considered fiveofthesixsubstances (allexcept MGA)
andmade recommendations onfourofthem (excluding trenbolone) during its32nd Session in1987.
Fortrenbolone, further datawassought andaJECFA recommendation made in1989. TheCCRVDF
considered theJECFA recommendations atitsmeetings in1987 andrecommended draftstandards
forthethree endogenous hormones andzeranol. These draftstandards wereapproved bytheCodex
Commission atStep5in1989. Standards forthese fourhormones wereconsidered atStep8bythe
Codex Commission inJune1991, but,following avoteonthematter, were notadopted. Adraft
standard fortrenbolone atStep5wasadopted on1991. InJune1995, theCodex Commission adopted
standards, atStep8,forthefivehormones, onthebasisofavote. These standards apply exclusively
withrespect tocattle, andmeatandmeatproducts ofbovine origin, when these hormones areused
forgrowth promotion purposes.
2.21 With respect tothethree natural hormones indispute, oestradiol-17 ,progesterone and
testosterone, similar Codex standards apply. Forthesethreehormones itwasconsidered "unnecessary "
toestablish anADIorMRL.8Specifically, theCodex states that:
"Establishing anADIandan[MRL] forahormone thatisproduced endogenously atvariable
levels inhuman beings wasconsidered unnecessary bytheCommittee. Residues resulting
fromtheuseofthissubstance asagrowth promoter inaccordance withgoodanimal husbandry
practice areunlikely toposeahazard tohuman health."9
2.22 The32ndJECFA Report of1988("1988 JECFA Report"), onwhich theCodex standards are
based, concluded thatresidues arising from theuseoftestosterone andoestradiol-17 asagrowth
promoter inaccordance withgood animal husbandry practice areunlikely toposeahazard tohuman
health andthattheamount ofexogenous progesterone ingested inmeatfrom treated animals would
notbecapable ofexerting anhormonal effect, andtherefore, anytoxiceffect, inhuman beings. Since,
according toJECFA, thepotential toxiceffect ofresidues ofthesehormones isdirectly related totheir
hormonal effect, theReport concluded thattheadditional residue levels intreated animals arenotcapable
ofexerting anytoxic effect. Onthebasis ofthissafety assessment andinviewofthedifficulty of
determining thelevels ofresidues attributable totheuseofthese hormones forgrowth promoting
purposes incattle (residues ofendogenous natural hormones inmeatcannot bepractically distinguished
from those exogenously administered), JECFA concluded thatitwas"unnecessary" toestablish an
ADIorMRL forthese hormones.
7Ibid.
8Ibid.,Section 1,pp.7, 12and14.
9Ibid,Section 1,footnote, pp.7, 12and14.WT/DS48/R/CAN
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2.23 With respect totwoofthesynthetic hormones atissue, zeranol andtrenbolone, theCodex
standards arethefollowing: anADIof0-0.5 and0-0.02 µg/kg bodyweight, respectively, andforboth
hormones anMRL of2µg/kg inbovine muscle and10µg/kg inbovine liver.
2.24 The1988JECFA Report, onwhich theCodex standard forzeranol isbased, noted thatzeranol
wasaweak oestrogen which mimicked theaction ofoestradiol-17 .Thereport concluded thatthe
toxic(incasutumorigenic) effect ofzeranol isassociated withitshormonal (i.e.oestrogenic) properties
andthatanADIcould thusbeestablished onthebasis ofano-hormonal-effect level. Adopting what
itconsidered tobeaconservative approach byusing asabasis studies onovariectomized female
cynomolgus monkeys (highly sensitive tooestrogenic substances) andusing asafety factor of100,
JECFA setanADIforhuman beings of0-0.5 µg/kg ofbody weight. Fora70kgperson consuming
500gofmeatdailyoveranentire lifetime, themaximum permissible orsafelevelofzeranol residues
inmeatwould then, according toJECFA, be70µg/kg ofedible tissue. However, thereport noted
thatwhen zeranol isadministered tocattle according togoodanimal husbandry practice, themaximum
mean residue levels didnotexceed 0.2µg/kg inmuscle, 10µg/kg inliver, 2µg/kg inkindney, and
0.3µg/kg infatatanytimeafterimplantation. These residue levels obtained onthebasis ofgood
animal husbandry practice arethusbelow themaximum permissible levelof70µg/kg. However, in
order tosetalevel which isdetectable byroutine residue analysis methods, theCodex MRL was
increased to2µg/kg inmuscle andsetat10µg/kg inliver.
2.25 Trenbolone acetate isthechemical form oresterusedfortheadministration oftrenbolone.
Trenbolone, ortrenbolone acetate ("TBA"), anandrogen which mimics theaction oftestosterone, is
rapidly hydrolysed afteradministration tocattle. Themajor metabolite (i.e.compound intowhich
TBA breaks down bychemical activity afterentering thebody) is-trenbolone, occurring interalia
inliver, and-trenbolone present inmuscle. Withrespect toTBA, the1988JECFA Report concluded
thatitspotential toxiceffects onlyariseasaconsequence ofitshormonal activity. Thereport further
concluded that,therefore, anADIcould beestablished onthebasis ofano-hormonal-effect level.
Adopting what itconsidered tobeaconservative approach byusing asabasis studies oncastrated
malerhesus macaque monkeys (which arehighly sensitive tocompounds withantigonadotropic activity)
andpigs(which areasensitive model forassessing hormonal effects ofTBA) andusing asafety factor
of100,JECFA latersetanADIforhuman beings of0-0.02 µg/kg ofbodyweight (34th JECFA Report
of1989). Themaximum ADIfora60kgperson would thusbe1.2µgofTBA residues. JECFA
thensetMRL'sfor-trenbolone inmuscle and -trenbolone inliver of2µg/kg and10µg/kg,
respectively, based onaverage residue levels inheifers at15-30 daysafterimplantation of300mg
TBA, noting thatconcentrations would beevenlower atproposed GPVD. According toJECFA, the
MRL'sthusobtained onthebasisofconservative estimates should notexceed theCodex ADIorsafe
levelatanytimeafterimplantation ofthedrug, thatis,irrespective ofthewithdrawal period used.
4. History ofevents
2.26 European consumers 'concern overtheuseofhormones forgrowth promotion purposes in
livestock grew steadily throughout the1970s astheresult oftheillegal useofdethylstilboestrol,
commonly known asDES (seeparagraph 4.183, footnote 130), invealproduction inFrance and
incidents, particularly inItaly, where adolescents hadbeenreported tobesuffering from hormonal
irregularities andvealhadcome under suspicion asapossible cause. European consumer organizations
called foraboycott ofveal, andthemarket forvealwasseverely affected. On20September 1980,
theECCouncil of(Agriculture) Ministers adopted adeclaration infavour ofabanontheuseof
oestrogen andendorsed theprinciple ofgreater harmonisation oflegislation onveterinary medicines
andofgreater control onanimal rearing, bothattheproduction andslaughtering stages.
2.27 On31October 1980, theECCommission proposed legislation aimed atbanning theuseof
allhormone products (COM (80)614), except fortherapeutic purposes. Thisproposal wasexpanded
laterbydocuments COM(80)920 andCOM(80)922, presented on6January 1981. These allowed forWT/DS48/R/CAN
Page9
thecontrolled usefortherapeutic andzootechnical purposes ofthree natural hormone products, and
introduced anumber ofcontrol measures ontheproduction andhandling ofsuchproducts, together
withproposals onthetesting ofanimals. On13February 1981, theEuropean Parliament adopted
the"Nielsen Report" approving theCommission proposals. TheECEconomic andSocial Committee
endorsed theproposals inFebruary 1981. However, three member States (Belgium, Ireland andthe
United Kingdom) sought tohavethethreenatural hormones remain available bothastherapeutic drugs
andasgrowth promotion agents, andIreland andtheUnited Kingdom alsoargued fortheretention
ofthesynthetic hormones, trenbolone andzeranol. Moreover, thirdcountries, including Argentina,
Australia, Canada, NewZealand, South Africa andtheUnited States, alsoraised questions concerning
theimpact ofanybanontheirexports totheEuropean Communities.
2.28 TheECCouncil ofMinisters adopted itsfirstDirective ontheissue (81/602/EEC) on
31July1981. InthatDirective, andinregard tofiveofthehormones atissue (allbutMGA), the
Council directed theCommission toprovide, notlaterthan1July1984, areport ontheexperience
acquired andscientific developments, accompanied, ifnecessary, byproposals taking intoaccount these
developments. Accordingly, theCommission setupaScientific Group onAnabolic Agents inAnimal
Production, chaired byProfessor G.E. Lamming (the"Lamming Group"). Thequestion addressed
totheLamming Group was:
"Does theuseforfattening purposes inanimals ofthefollowing substances: oestradiol-17 ,
testosterone, progesterone, trenbolone andzeranol present anyharmful effect tohealth."10
"TheLamming Group issued aninterim report on22September 1982(the"Lamming Report").
TheLamming Report concluded asfollows:
"The Scientific Working Group isoftheopinion thattheuseofoestradiol-17 ,testosterone
andprogesterone andthose derivatives which readily yieldtheparent compound onhydrolysis
afterabsorption fromthesiteofapplication would notpresent anyharmful effects tothehealth
oftheconsumer when usedunder theappropriate conditions asgrowth promoters infarm
animals.
"Evaluation ofdataon"trenbolone" and"zeranol" revealed thatsome dataonthehormonal
non-effect-level andthetoxicology ofthese compounds andtheirmetabolites arestillmissing.
"TheScientific Working Group considers itnecessary thatadditional information beprovided
before afinalconclusion canbegiven ontrenbolone andzeranol.
"Proper programmes tocontrol andmonitor theuseofanabolic agents areessential.
"Itisnecessary tocontinue scientific investigations ontherelevance ofthepresent useofthe
"no-hormone-effect" levelrelated totheharmful effects ofanabolic agents."
2.29 TheECScientificVeterinaryCommitteegaveitsreactiontotheLammingReporton9November
1982, followed bytheECScientific Committee forAnimal Nutrition on17November 1982 andby
theECScientificCommitteeforFoodon4February1983.TheseCommitteessupportedtheconclusions
andrecommendations oftheLamming Report, butstressed theneedtolaydown provisions regarding
theestablishment ofproper programmes tocontrol andmonitor theuseofanabolic agents withregard,
inparticular, toinstructions foruse,surveillance programmes andanalysis methods. InJanuary 1984,
theCommission asked agroup ofexperts within theECScientific Committee onAnabolic Agents to
review theinformation ontrenbolone andzeranol. On12June1984, theCommission published a
10Report ofthe(EC) Scientific Veterinary Committee, Scientific Committee forAnimal Nutrition andtheScientific
Committee forFood ontheBasis oftheReport oftheScientific Group onAnabolic Agents inAnimal Production, pp.1and12.WT/DS48/R/CAN
Page10
proposal(COM(84)295final)foraCouncilDirectiveamendingDirective81/602/EEC,whichenvisaged
thecontrolled useofthethree natural hormones forgrowth promotion purposes andproposed re-
examining thebanonthetwosynthetic hormones aftertheirscientific evaluation hadbeencompleted.
However, theEuropean Parliament, theECEconomic andSocial Committee andtheECCouncil of
Ministers rejected theCommission 'sproposal.
2.30 TheECCommissionamendeditsproposalaccordinglyandon31December1985theECCouncil
adopted Directive 85/649/EEC. ThisDirective confirmed thebanontheuseofallthesubstances
concernedforgrowthpromotionpurposesandestablishedmoredetailedprovisionsconcerningauthorized
therapeutic uses. TheDirective waschallenged intheEuropean Court ofJustice, which annulled it
onprocedural grounds. Theproposals werere-introduced bytheECCommission andre-adopted by
theECCouncil asCouncil Directive 88/146/EEC on16March 1988.
2.31 Followingreportsofsignificantuseofillegalgrowth-promotinghormonalsubstancesinanumber
ofECmember States, on26September 1988 theEuropean Parliament established a"Committee of
Enquiry intotheProblem ofQuality intheMeat Sector". TheReport ofthisCommittee (the"Pimenta
Report") endorsed thebanontheuseofhormones andwasadopted bytheEuropean Parliament on
29March 1989 (seeparagraph 4.19). Theessential findings ofthePimenta Report were thatthe
prohibition ofhormonal substances fornon-therapeutic (i.e.growth-promoting) purposes must be
maintained andexpanded because:
(i) thiswastheonlywaytorestore consumer confidence inthemeatsector;
(ii) 10outof12national veterinary experts indicated thatatotalbanwould facilitate
implementation andcontrol;
(iii) thescientific conclusions regarding theuseofnatural hormones rested upon strict
conditions ofusewhich itbelieved could notinreality beattained. TheCommittee
wasoftheopinion thatuseofthenatural/nature-identical hormones carried therisk
ofinexperienced application, incorrect dosage andunsupervised injection which could
posearisktotheanimal andtheconsumer, andalsonoted doubts withregard tolong-
termcumulative andinteractive potential carcinogenicity. Inaddition, theCommittee
believed thatproven necessity andsocio-economic desirability should becriteria of
acceptability fortheuseof(bio)chemical growth promoters inanimal-rearing;
(iv) TheCommittee didnotaccept theargument thatprohibiting theuseforgrowth
promotion ofsome natural ornature-identical hormones would result inanincrease
intheuseofother, more dangerous growth-promoting substances tothedetriment of
theconsumer;
(v) theCommittee believed thattheCommission should promote theconcept ofanimal
welfare inagricultural production.
2.32 TheEuropean Parliament adopted another report ontheissue ofuseofhormones foranimal
growth promotion, the"Collins Report" of7February 1989.11Thisreport argued that:
"Current licensing systems fortheregulation ofveterinary medicines (including atpresent,
growth promoting products) require thatanewproduct satisfy three criteria: safety, quality
andefficacy. These criteria maywellbesatisfactory fortherapeutic drugs. They arebyno
11European Parliament, Committee ontheEnvironment, Public Health andConsumer Protection, Report on"The USA's
Refusal tocomply withCommunity legislation onslaughterhouses andhormones andtheconsequences ofthisrefusal",
EP128381/B, 7February 1989, named after itsreporter Mr.Collins, MEP.WT/DS48/R/CAN
Page11
means sufficient forgrowth promoting products. Forthelatter itisproposed herethatthe
Community 'sveterinary medicine licensing system beadapted toinclude a"fourth hurdle",
entailing anobjective socio-economic andenvironmental impact assessment" .Inthe
Commission 'sJuly1988 draftproposals forthereform ofveterinary medicine licensing in
theCommunity thisideawasaccepted inprinciple. Thefinal version oftheproposals
(December 1988) doesnotinclude thisconcept. Itisclear, however, thatthesocial, agricultural
andenvironmentalimplicationsoftheuseofgrowthandyieldpromotingpharmaceuticalsrequire
alicensing system somewhat different from thatwhich exists forthese products when used
fortherapeutic purposes".
2.33 TheECCommission organized ascientific conference onthissubject inBrussels from
29November to1December 1996. With regard tothenatural hormones, the1995 ECScientific
Conference onGrowth Promotion inMeatProduction (the"1995 ECScientific Conference") concluded
that:
"Atpresent, there isnoevidence forpossible health riskstotheconsumer duetotheuseof
natural sexhormones forgrowth promotion, since:
Residue levels ofthese substances measured inmeatoftreated animals fallwithin the
physiological range observed inmeatofcomparable untreated animals.
Thedaily production ofsexhormones byhumans ismuch higher thantheamounts
possibly consumed frommeat, eveninthemostsensitive humans (prepubertal children
andmenopausal women).
Duetoanextensive first-pass metabolism, thebioavailability ofingested hormones
islow,thusproviding afurther safety margin."12
With regard tothesynthetic hormones, zeranol andtrenbolone, the1995 ECScientific Conference
concluded that:
"Atthedoses needed forgrowth promotion, residue levels [oftrenbolone andzeranol] are
wellbelow thelevels regarded assafe(theMRLs). There are,atpresent, noindications of
apossible human health riskfromthelowlevels ofcovalently-bound residues oftrenbolone."13
III. CLAIMS OFTHE PARTIES
3.1 Canada claimed thattheECmeasures were governed bytheSPSAgreement andthatthe
European Communities, bybanning theimportation ofmeatandmeatproducts fromanimals towhich
anyofthesixhormones hadbeenadministered forpurposes ofpromoting thegrowth ofanimals, had
acted inconsistently withtheSPSAgreement, inparticular Articles 2,3and5.TheECmeasures were
notbasedonanappropriateriskassessment;failedtotakeintoaccountinternationalstandards,guidelines
andrecommendations intheabsence ofscientific justification; wereused, inpart,asameans tocontrol
domestic production; andwere more restrictive thanrequired tomeet their appropriate level of
protection. These measures were farmore restrictive than measures adopted bythe
European Communities tocontrol theuseofother substances usedinanimal husbandry thatpresented
ademonstrably greater risktohealth thanthesixhormones atissue. TheEClevelofprotection for
growth promoting hormones wassignificantly higher thantheEClevelofprotection forantimicrobial
12"Assessment ofHealth Risk-Working Group II",in1995 ECScientific Conference Proceedings, pp.20-21.
13Ibid.WT/DS48/R/CAN
Page12
growthpromotersandotherveterinarydrugs,resultinginadiscriminationagainstCanadianbeefimports
andadisguised restriction oninternational trade.
3.2 Canada alsoclaimed thattheECmeasures were contrary toGATT, inparticular Article III
orXI.Canada argued thattheECmeasures were either animport prohibition, incontravention of
GATT, orinternal measures thatdiscriminated infavour ofECcattle andbeefproducts, andagainst
likeCanadian cattle andbeefproducts, alsocontrary toGATT.
3.3 Canada submitted alternative arguments thatthemeasures atissuealsofailed tomeetobligations
under theTBTAgreement, inparticular Article 2,intheevent itwasfound tobeapplicable.
3.4 Canada claimed thattheapplication oftheECmeasures otherwise nullified orimpaired the
benefits accruing toCanada pursuant totheAgreement Establishing theWorld Trade Organization
("WTO Agreement") respecting market access forbeef.14
3.5 TheEuropean Communities considered thattheanalysis oftheSPSand/or TBTAgreements
should takeplace onlyifalleged violations ofGATT Articles werefound andtherefore, initsdefense,
theEuropean Communities firstinvoked GATT. Withregard tothealleged violation ofArticle III:4
ofGATT, theEuropean Communities argued thattheanimals towhich thehormones atissuehadbeen
administered forgrowth promotion, andmeatfromthose animals, werenot"like" other animals and
meat from those animals, respectively. Furthermore, theEuropean Communities argued thateven
iftheywere found tobe"like", imported products were notgiven "less favourable treatment" than
domestic products. Therefore, theEuropean Communities claimed thatitsmeasures didnotinfringe
Article III:4 ofGATT. With regard tothealleged violation ofArticle XIofGATT, the
European Communities claimed thattheECmeasures atissuewereinternal regulations within thescope
ofArticle IIIofGATT. Therefore, Article XIofGATT didnotapply. TheEuropean Communities
claimed thatincaseitsmeasures were found tobecontrary toArticle III:4, itwasjustified by
Article XX(b), which didnotaffect thepower ofaMember toadopt apolicy inorder toprotect human
andanimal health.
3.6 TheEuropean Communities claimed thatthemeasures atissue, inanyevent, didnotviolate
anyprovision oftheSPSAgreement because theysatisfied alltheconditions imposed byit.The
measures were based onscientific principles asrequired byArticle 2.2oftheSPSAgreement, and
ariskassessment hadbeenperformed which established thescientific basisforregulatory action. The
European Communities observed thattheSPSAgreement recognized aMember 'srighttoestablish
thelevel ofprotection which theMember determined tobeappropriate within itsterritory. The
European Communities claimed thattheSPSAgreement didnotrequire Members tochange thelevel
ofsanitary protection theywereapplying before itsentry intoforce. TheEuropean Communities also
claimed thatthemeasures atissue werebased onscientific principles andaimed atachieving alevel
ofprotection which washigher thancould beachieved iftherecommendations ofCodex forthese
hormones werefollowed, because more recent scientific evidence showed thatthese hormones were
genotoxic andcarcinogenic. Italsoclaimed thatWTO dispute settlement panels werenotcompetent
tojudge itslevelofsanitary protection northescientific evidence upon which itwasbased, butonly
whether itsmeasures wereinconformity withtheprovisions oftheSPSAgreement. Itfurther claimed
14Uruguay Round Schedule LXXX -European Communities, PartIMost Favoured-Nation Tariff, Section I-Agricultural
Products, Section IATariffs andSection IBTariff Quotas, assubsequently modified. Tariff items covered bytheECbeef
andvealregime are:
02011050; 02012015; 02012035; 02012055; 02012090; 02013000; 02021000; 02022010; 02022030;
02022050; 02022090; 02023010; 02023050; 02023090; 02061010; 02061091; 02061095; 02061099;
02062100; 02062210; 02062290; 02062910; 02062991; 02062999; 02102010; 02102090; 02109041;
02109049; 16025010; 16025090; 16029061; and16029069.WT/DS48/R/CAN
Page13
thatthearguments ofCanada infactattacked theECchosen levelofprotection, notitsmeasures, because
theysuggested thatresidues ofthese hormones above naturally present levels didnotposeanyrisk
tohealth. TheEuropean Communities claimed thattheSPSAgreement laiddown theobjective of
avoiding arbitrary orunjustifiable distinctions inapplying thechosen levels ofprotection (notbetween
measures usednorbetween riskspresented byother substances), andonlyifsuchdistinctions resulted
indiscrimination oradisguised restriction ontrade. TheEuropean Communities further claimed that
itsmeasures werebased ontheprecautionary principle. Itmaintained thatitsmeasures werenomore
traderestrictive thanrequired toachieve itsappropriate levelofsanitary protection andapplied inexactly
thesame waytoallanimals treated withthese hormones andmeatfrom suchanimals, whatever its
origin; therewasconsequently nodiscrimination nordisguised restriction oninternational trade. The
European Communities alsoclaimed thatCanada failed todischarge itsburden ofproof because ithad
failed toshow onthebasisofcurrent scientific evidence thatmeatcontaining residues ofthesehormones
wassafeforhuman consumption andthatthere existed another measure, reasonably available taking
intoaccount technical andeconomic feasibility, which could achieve theECappropriate levelofsanitary
protection andwassignificantly lessrestrictive ontrade.
3.7 TheEuropeanCommunitiesclaimedthatthemeasuresatissuefelloutsidethescopeofapplication
oftheTBTAgreement because theyweresanitary measures within themeaning oftheSPSAgreement.
Inthealternative, theECclaimed thatthemeasures atissue didnotviolate Articles 2.1and2.2of
theTBTAgreement because theirlegitimate objective wastoprotect human andanimal health and
they were notmore trade restrictive than necessary toachieve thisobjective. Finally, the
European Communities claimed thatitsmeasures didnotnullify orimpair thebenefits accruing to
Canada pursuant totheWTO Agreement, because thebenefits claimed byCanada weregranted after
theadoption oftheECmeasures, could havebeenreasonably anticipated byCanada anddidnotupset
thecompetitive relationship between domestic andimported products.
IV. ARGUMENTS OFTHE PARTIES
1. Relationship between GATT andtheSPSAgreement
4.1 Canada claimed thattheSPSAgreement, GATT andtheTBTAgreement wereagreements
ofequal status, contained inAnnex 1AoftheWTO Agreement (asperArticle IIoftheWTO
Agreement). Since theSPSAgreement contained rulesthatweremore detailed andmore precise than
those oftheGATT, itwasappropriate toexamine firsttheapplication oftheSPSAgreement tothe
ECmeasures, followed byGATT.
4.2 TheEuropean Communities considered thattheSPSAgreement would apply onlyifaviolation
oftheArticles ofGATT were tobeestablished. TheEuropean Communities argued thattheSPS
Agreement codified, asthelastrecital ofitspreamble stated, thedesire ofMembers "toelaborate rules
fortheapplication oftheprovisions ofGATT which relate totheuseofsanitary orphytosanitary
measures, inparticular theprovisions ofArticle XX(b)". Furthermore, itwaswellestablished GATT
lawandpractice thatGATT 1947didnotaffect thepower ofitsmembers tosetuparegulatory policy
which theydeemed necessary inorder toprotect human, animal orplant health. Buttheconformity
ofthemeasures itapplied forthatpurpose could bereviewed under GATT.15Itwas,therefore, admitted
thataviolation ofGATT byameasure should beestablished first, before recourse topossible
justifications (e.g.under Article XX(b)) could beconsidered. Insuchanevent, thePanel could review
themeasure butnottheunderlying policy objective onwhich itwasalleged tobebased. TheEuropean
Communities noted thattherewereseveral newprovisions intheSPSAgreement thatimposed aseries
ofrights andobligations onMembers. However, theSPSAgreement reaffirmed therightofMembers
15Insupport ofitsargument, theEuropean Communities referred tothepanel report on"Thailand -Restrictions on
Importation ofandInternal Taxes onCigarettes", adopted 5October 1990, DS10/R.WT/DS48/R/CAN
Page14
toadopt orenforce measures theMember deemed tobenecessary toprotect human, animal orplant
health (recitals 1and6ofpreamble). Itcould therefore beargued thatmostoftheobligations created
bytheSPSAgreement werealready applied under GATT 1947through interpretations ofArticle XX(b)
bypanel reports andtheCONTRACTING PARTIES.
4.3 TheEuropean Communities claimed thatArticle 2.4oftheSPSAgreement established that
SPSmeasures which conformed totheAgreement were "presumed" tobeinaccordance withthe
obligations oftheMembers "under theprovisions ofGATT which relate totheuseofsanitary or
phytosanitary measures, inparticular theprovisions ofArticle XX(b)" (emphasis added). Despite
thefactthatthewords "inparticular" appeared inArticle 2.4,itwashardtoimagine other provisions
ofGATT "which relate totheuseofsanitary orphytosanitary measures". Therefore, iftheSPS
Agreement weretobedefined asaself-standing agreement thiswasnotbecause itinterpreted provisions
ofGATT other thatArticle XX(b), butonlybecause itlaiddown additional procedural requirements.
Thesubstantive roleoftheSPSAgreement wastointerpret Article XX(b) ofGATT; recourse tothe
substantive provisions oftheSPSAgreement could bemade onlyunder thesame conditions under
which recourse could bemade toArticle XXofGATT, thatwasonlyafteraviolation ofanother
provision ofGATT wasfirstestablished. Asfarastheadditional, procedural obligations laiddown
bytheSPSAgreement, these could beexamined bythePanel directly andindependently ofanyneed
toestablish firstaviolation oftheprovisions ofGATT.
4.4 Canada disagreed thatthesubstantive mission oftheSPSAgreement was"tointerpret
Article XX(b) ofGATT", withtheaddition ofafewprocedural rules, andthat"...recourse tothe
substantive provisions oftheSPSAgreement could bemade onlyunder thesame conditions under
which recourse could bemade toArticle XXGATT, thatisonlyafteraviolation ofanother provision
ofGATT wasfirstestablished". Canada responded that,theSPSAgreement wasaself-standing
agreement ofequal status totheGATT. Article 1oftheSPSAgreement provided thattheAgreement
"applies toallsanitary andphytosanitary measures which may,directly orindirectly, affect international
trade." There wasnorequirement thataviolation ofGATT must beestablished before theSPS
Agreement applied. TheECmeasures hadaprofound anddirect effect onCanadian beefexports to
theEuropean Communities, sotherewasnoquestion thattheECmeasures directly affected international
trade. TheEuropean Communities agreed thatitsmeasures weresubject totheSPSAgreement. Thus,
inaccordance withtheordinary meaning tobegiven totheterms setoutinArticle 1,theonlycondition
forapplying theSPSAgreement hadbeenmet.
4.5 Canada further argued thattheSPSAgreement wasclearly more thanjustaninterpretation
ofArticle XX(b). Forexample, Articles 3and4,on"Harmonization" and"Equivalence" respectively,
didnotcorrespond toanyprovision intheGATT, andwere more than"...additional procedural
requirements". Thebroad scope oftheSPSAgreement wasreflected inthefourth andsixthpreambular
paragraphs, which stated thedesire oftheWTO Members toestablish "amultilateral framework of
rulesanddisciplines toguide thedevelopment, adoption andenforcement ofsanitary andphytosanitary
measures inorder tominimize theirnegative effects ontrade" andto"further theuseofharmonized
sanitary andphytosanitary measures between Members, onthebasis ofinternational standards ...".
Finally, thenegotiating history confirmed thattheSPSAgreement wasmore thananinterpretation
ofArticle XX(b). Intheearly stages oftheUruguay Round, ithadbeen drafted asaDecision
interpreting theGATT 1947, butlaterevolved toaself-standing agreement inAnnex 1A. Ifthe
negotiators hadintended thattheSPSAgreement would bemerely aninterpretation ofArticle XX(b),
itwould have been incorporated intotheGATT asan"Understanding ontheInterpretation of
Article XX(b)", rather thananindependent agreement.
2. TheSPSAgreement
4.6 Canada noted thathistorically theECmeasures hadbeenmotivated byfoursetsofconcerns:
(i)anxiety regarding thedanger tohuman health occasioned bytheillegal useofsubstances, suchasWT/DS48/R/CAN
Page15
DES(seeparagraph 4.183, footnote 130); (ii)thepressure ofpublic opinion which, under prevailing
circumstances, didnotdistinguish between products ortheconditions oftheiruse;(iii)theeconomic
consequences ofa"sensationalist campaign"16,which hadresulted inthecollapse ofthevealmarket
andasharp decline inbeefconsumption throughout theEuropean Communities; and(iv)thedistortions
intheconditions ofcompetition among theECmember States owing todissimilar provisions and
regulations governing themanufacture, distribution anduseofsubstances.17
4.7 Canada recalled theterms ofreference andconclusions oftheLamming Report (see
paragraph 38).Although theLamming Group wassuspended bytheECCommission before ithad
completed itsterms ofreference, ithadsubsequently produced asecond report inOctober 1987, stating
thatthelevels oftrenbolone andzeranol andtheirmajor metabolites found inedible tissue, following
accepted husbandry practices, weresubstantially below thehormonally effective doses inanimal test
systems andtherefore didnotpresent aharmful effect tohealth.
4.8 Canada observed thatinitsproposal published inJune 1984 (COM(84)295 final, see
paragraph 39),theECCommission hadsetoutthreeconditions fortheuseofthesehormones forgrowth
promoting purposes: theycould beadministered onlybyimplantation inapartoftheanimal which
would bediscarded atslaughter; treated animals hadtobeidentified atthetimeofimplantation; and
theimplants were tobeadministered byaveterinarian. Canada argued thattheECCommission 's
proposal hadbeenrejected bytheEconomic andSocial Committee because ofconcerns thattheEC
Commission 'sproposal would overturn whattheEconomic andSocial Committee hadseentobethe
twocentral objectives ofboththeoriginal Directive andtheECCommission 'sproposed Directive,
which "...make theprotection oftheconsumer 'shealth andeconomic interests priority objectives".18
4.9 Canada claimed thatinrejecting theproposal toallow theuseofthethree natural hormones,
theEconomic andSocial Committee hadclearly disregarded thefindings oftheScientific Working
Group. Insupport ofitsposition, theEconomic andSocial Committee hadpointed tothefact,that
"...on30September 1980theCouncil undertook unanimously, under thepressure ofpublic opinion,
toprohibit theadministering ofallhormones ...inlivestock production".19TheEconomic andSocial
Committee hadalsonoted that,although consumer groups andworkers hadlongbeenunequivocally
opposed totheuseofanabolics, neither farmers 'organizations normeatprocessors andtraders had
taken anofficial stand attheEClevelonthisissue. Professor Lamming himself, inapresentation
in1986, hadbeenunequivocal inhisassessment ofthereasons behind thesuspension oftheLamming
Group andtherejection oftheECCommission proposal based ontheLamming Group 'sfindings with
respect tothethree natural hormones:
"The British Minister hasclaimed, andrightly so,that[ECAgriculture Commissioner]
Andriessen freely admits thatthescientific background orscientific consideration were not
taken intoaccount. Inother words itwaspurely apolitical decision andifyoureadthespeeches
thatwere made intheEuropean Parliamentary debate theyaremainly based onthefactthe
[sic]wehavegotsuchasurplus ofbeefanditcosts aheckofalottostore it,whyshould
weauthorize anytechniques which aregoing toincrease thatproductivity. Themajority of
16J.B.Nielsen (1981), "Report drawn uponbehalf oftheCommittee onAgriculture ontheproposals fromtheCommission
totheEuropean Communities totheCouncil ...",European Parliament, Doc. I-840/80 (the"Nielsen Report").
17Ibid.,Doc. 1-523/80.
18"Opinion ontheproposal foraCouncil Directive amending Directive 81/602/EEC concerning theprohibition ofcertain
substances having ahormonal action andofanysubstances having athyrostatic action" (1985), ECOfficial Journal (85/C
44/11) (C44),p.14.
19Ibid.,p.15.WT/DS48/R/CAN
Page16
European parliamentary members could seethisasaprevention ofanincreased production
ofEuropean beefandthatprobably motivated them more thanthescientific background."20
4.10 Moreover, theresolution oftheEuropean Parliament (February 1988), hadstated that"...the
Community, withitsdirectives banning hormones, hasadopted consistent legislation bothinterms
ofthenecessary control ofagricultural production andfromthepointofviewofprotecting theinterests
ofconsumers".21Canada pointed outthatthepreamble ofDirective 88/146/EEC setouttherationales
fortheprohibition. These were: toharmonize theregulatory schemes oftheECmember States;
remove competitive distortions andbarriers tointra-Community trade; meetconsumer anxieties and
expectations; andbring about anincrease intheconsumption ofmeatproducts.22Thiswaskeeping
withtheopinion oftheSocial andEconomic Committee23,aswellastheResolution oftheParliament
of11October 1985.24
4.11 Canada submitted thatSirJohn Maddox, Editor ofNature andChairman ofthe1995 EC
Scientific Conference, hadtouched ontwopoints thathadbeenatthecentre oftheargument regarding
theEChormoneslegislation.Hehadnoted,first,thatthe1995ECScientificconferencehadreconfirmed
thescientific argument thatthesehormones "were notdamaging tomeat-eating consumers".25Second,
hisarticle hadhighlighted thepoliticized nature ofthisdebate within theEuropean Communities and
howthathadbeenreflected inthecomposition andproceedings ofthe1995ECScientific Conference
itself. Scientists wereoutnumbered byparticipants frombodies suchastheEuropean Parliament, the
Economic andSocial Committee andvarious lobby groups, allofwhich hadbeenlong-time advocates
oftheECmeasures atissue. Inabrief paper forwarded totheEuropean Communities following
publication oftheproceedings, twoCanadian scientists, oneofwhom hadparticipated intheEC
Conference, commented notonlywere scientists outnumbered bynon-scientists but,asnoted inthe
"Report andConclusions" oftheConference proceedings "...thefinalplenary session ofthewhole
conference, apart from abriefstatement oftheprincipal conclusions bythechairman, waslargely
dedicated tostatements bythose notinvited asscientist-participants".26Canada further criticized the
20"Anabolic Growth Promotants andtheEEC," supra, note63,p.11.
21"Resolution onthebanonhormones", 1988 ECOfficial Journal (C68)103.
22Ibid.,Therelevant portions ofthepreamble state:
"Whereas theadministration tofarmanimals ofcertain substances having ahormonal action isatpresent regulated
indifferent ways inthemember States; whereas while theirimmediate effect onanimals from thefarmer 'sview
isclear, assessments ontheireffect onhuman health varyandthisisreflected inthevariations governing their
use;whereas thisdivergence distorts theconditions ofcompetition inproducts thatarethesubject ofcommon market
organizations andisaserious barrier tointra-Community trade;
"Whereas these distortions ofcompetition andbarriers totrade must therefore beremoved byensuring thatall
consumers areabletobuytheproducts inquestion under largely identical conditions ofsupply andthatthese products
correspond totheiranxieties andexpectations inthebestpossible manner; whereas suchacourse ofaction isbound
tobring about anincrease inconsumption oftheproduct inquestion."
23"Opinion ontheproposal foraCouncil Directive amending Directive 81/602/EEC" (1985), ECOfficial Journal
(85/C44/11) (C44),p.14.
24"Resolution closing theprocedure forConsultation oftheEuropean Parliament ontheproposal from theCommission
oftheEuropean Communities totheCouncil foraDirective amending Directive 81/602/EEC" (1985), ECOfficial Journal
(C288), p.158.
25J.Maddox, "Contention overgrowth promoters" (1995) 378 Nature 553.
26SteeringCommittee,"ReportandConclusions,"in1995ECScientificConferenceProceedings(Luxembourg:European
Commission, 1996), p.3.WT/DS48/R/CAN
Page17
exclusion ofscientists directly employed bycommercial companies withaninterest inthesaleofgrowth
promoters, despite thefactthatthese companies "hold much oftheproprietary information thatis
required forreview bynational regulatory agencies andinternational bodies suchasJECFA"; and
argued thatsince theconference papers represented individual opinions, "[t]he scientific validity of
these conference papers doesnotcompare withtheexpert committee reviews andrecommendations
ofJECFA, orwiththeregulatory review process inaregistering country".27
4.12 TheEuropean Communities responded thattheLamming Group hadbeendissolved because
itwasovertakenbyevents.DuringthedeliberationsoftheLammingGroup,theECCouncilhaddecided
toadopt alevelofprotection which avoided thepresence ofanyadded hormones inmeat. Thishad
made thework ofthatgroup redundant, which was already lateinissuing itsreport.
Professor Lamming 's1987 account offurther work undertaken bymembers ofhisgroup onzeranol
andtrenbolone had,similarly totheconclusions inthe1982 Lamming Report (seeparagraph 38),
concluded thatthese substances would probably besafewhen usedinaccordance with"accepted
husbandry practice" -atermhehadnotdefined.28TheEuropean Communities contended, furthermore,
thattheseconclusionswerebasedontheunsupportedassumptionthatthecarcinogenicityofthesubstances
wasrelated totheirhormonal effects andthatresidues oftrenbolone andzeranol andtheirmetabolites
didnotshow "significant genotoxic potential". TheEuropean Communities argued thatthecommon
theme ofthisscientific advice, therefore, wasthatproper systems ofcontrol andmonitoring would
beapre-requisite fortheuseofhormones forgrowth promotion. However, noneofthese scientific
reports hadexplained whatconstituted "appropriate conditions ofuse"norhadtheydefined whatwas
"good animal husbandry practice". Instead, theyhaddrawn theattention oftheECCommission to
theneedtolaydown theessential conditions concerning use,detection andcontrol ofthese hormones
iftheywere tobeallowed forgrowth promotion.
4.13 TheEuropean Communities argued thatthereported opinion ofProfessor Lamming, whowas
relaying information reported tohavebeenmade tohimbytheUnited Kingdom Minister ofAgriculture,
didnotconform withtheofficial andpublicly available views expressed byMr.Andriessen. The
European Communities noted thatMr.Andriessen hadsaid,forexample, that"theECCommission
recognizes thatsome scientists consider that,subject tocertain conditions, thehormones could safely
beusedforfattening purposes inanimals. TheCommission is,however, oftheopinion thatthese
substances mustbeproperly considered asmedical substances which areonlyusedforveterinary medical
purposes, andonlyunder strict conditions ofsupervision andcontrol".
4.14 TheEuropean Communities asserted thatthehistorical record clearly demonstrated thatthe
purpose oftheECmeasures wastoprotect human andanimal health from risksarising fromtheuse
ofthehormones atissue. TheEuropean Communities noted thattheEuropean Parliament hadbanned
imports ofmeatfromanimals treated withgrowth promoting hormones primarily because "scientific
information about these substances isfarfrom complete andthatconsiderable doubt therefore exists
about thedesirability oftheiruseandoftheireffect onhuman health".29Serious health concerns had
beenclearly stated indifferent MEP reports, including the"Nielsen Report", the"Pimenta Report"
andthe"Collins Report", andtheEuropean Parliament hadremained constantly opposed tothe
authorizationofallthesehormonesforanimalgrowthpromotingpurposesforreasonsofpossiblehazards
tohuman andanimal health.
4.15 When theECCommission hadfirstproposed in1980 totakemeasures inthisarea, aswell
asin1988, ithadfound itself facing certain factual, legalandscientific situations. From thefactual
27J.D.MacNeil &Yong, "Canada 'sComments ontheEUScientific Conference, Report andConclusions, 23July1996.
28Published inTheVeterinary Record (24/10/1987, p.389).
29Point EofParliament 'sResolution, ECOfficial Journal, No.288, 11November 1985, p.158.WT/DS48/R/CAN
Page18
point ofview, consumer concerns overtheuseofhormones forgrowth promotion inlivestock was
veryhigh. Despite thetraditionally cautious approach totheregulation ofdangerous substances followed
bytheECmember States, consumer confidence inscience andregulators (especially among well-
informed consumer organisations andgroups) wasverylow. Thisfactual situation hadnotchanged
during theentire period thathadpreceded theadoption ofDirective 96/22/EC; consumer concerns
were evenhigher today.
4.16 TheEuropean Communities noted thatfrom thelegalpoint ofview, theuseofhormones in
animalgrowthpromotionhadlongbeenprohibitedinmostECmemberStates,butsomeofthemallowed
theuseofsome ofthese substances under certain conditions.30With theprogressive establishment
ofthecommon market, thedivergence inthelegislation oftheECmember States wasinhibiting free
trade within theEuropean Communities inanimals andmeatfromanimals treated withsome ofthese
hormones, anddistorting theconditions ofcompetition among ECmeatproducers.
4.17 Furthermore, theEuropean Communities observed thatfromthescientific point ofview, the
situation wasveryunclear intheearly 1980s. Therelevant international organizations -FAO, WHO,
theOffice international desépizooties (OIE) andCodex -hadstarted toseriously examine thesafety
ofthesehormones inmeatproduction onlyduring the1980s. Thefirstsubstantive andcomprehensive
scientific report hadbeenpublished byOIEin1983. JECFA haddiscussed andissued asubstantive
andcomprehensive scientific report onthesehormones onlyin1988. There weretwootherinternational
reports comprising collective scientific work: the1984 Scientific Report published bytheEuropean
Commission (based ontheLamming Report) andtheProceedings ofthe1995ECScientific Conference.
TheEuropean Communities stressed, however, thatthese reports didnotconstitute theentire body
ofscientific knowledge ontheissueofsafeuseofthese hormones forgrowth promotion. There were
alsoimportantstudiesmadebyindividualscientists,andotherspecializedinstitutionsliketheInternational
Agency forResearch onCancer ("IARC")
4.18 TheEuropean Communities recalled thattheECCommission proposal (COM(84)295 final),
which finally hadledtotheadoption ofDirective 88/146/EEC, proposed toallow theuseofthethree
"natural" hormones onlyunder thefollowing conditions inorder tosafeguard public health:
- onlyintheform ofanimplant tobeadministered inapartoftheanimal discarded
atslaughter (usually theear);
- toanidentified animal only, toallow control ofthewithdrawal period;
- onlybyaveterinarian, withalltreatments recorded;
- substancesallowedtobeadministeredmustbeonaEClist,clearlysettingoutconditions
ofuse;
- these substances must beshown tobeeffective andsafe;and
- meatproduced fromtreated animals mustbeidentified assuchtothefinalconsumer.
TheEuropean Communities indicated thattheEconomic andSocial Committee hadbased itsrefusal
oftheECCommission proposal COM(84)295 finalontheneedforscientific evidence and"particular
30TheEuropean Communities indicated thatthere wasanumber ofmember States (probably 4or5)which didallow
theuseofsome ofthese hormones forgrowth promotion untiltheirprohibition atEClevel. Theinformation onpercentages
ofuse,ifitwasavailable atall,would onlybeknown totheindividual member States which approved theuseoftheparticular
substances. Atleastonemember State (theUnited Kingdom) hadindicated that"anecdotal evidence suggests thatgrowth
promoting hormones mayhave been used onupto40% ofUnited Kingdom cattle prior totheban".WT/DS48/R/CAN
Page19
reference tohealth aspects ".31Moreover, theEuropean Parliament hadeventually decided toreject
theECCommission proposal, considering that"scientific information about these substances isfar
from complete andthatconsiderable doubts therefore existabout thedesirability oftheiruseandof
theireffect onhuman health".32Theproposal oftheCommission hadalsobeenrejected bytheEC
Council ofMinisters ontheadditional grounds thattheproposal wasnottechnically oreconomically
feasible (seeparagraph 4.131).
4.19 TheEuropean Communities indicated thatin1988, following discoveries ofsignificant use
ofillegal growth-promoting hormonal substances incertain ECmember States, theEuropean Parliament
hadestablished a"Committee ofEnquiry intotheProblem ofQuality intheMeatSector".33ThisInquiry
Committee hadreceived submissions from awide range ofscientific experts, organisations and
institutions,includingmeattradeandfarmers'organisations,thirdcountryproducers,thepharmaceutical
industry andconsumers 'organizations. Theoutcome ofthework oftheCommittee ofEnquiry into
theProblem ofQuality intheMeatSector, thePimenta Report, wasadopted bytheEuropean Parliament
on29March 1989. Thereport observed that:
"1. TheInquiry Committee considers thattheprohibition ofhormonal substances fornon-
therapeutic (i.e.growth-promoting) purposes, aslaiddown inDirectives 81/602/EEC
and88/146/EEC mustbemaintained andexpanded withthefollowing justifications:
(a) theInquiry Committee believes thatthemaintenance andreinforcement ofthetotal
banontheuseofhormonal andother growth-promoters istheonlywaytorestore
consumer confidence inthemeat sector andtoclarify thisverycomplex issue for
producers andconsumers alike;
(b) theInquiryCommitteeisconvincedthatcontrolmeasureswillhavetobecomprehensive
andaccepts theopinion of10outof12national veterinary experts thatatotalbanwill
facilitate implementation andcontrol;
(c) theInquiry Committee takesnoteofthescientific evidence thathasbeenplaced before
it,andpoints outthattheconclusions regarding theuseofnatural andnature-identical
hormones restupon strict conditions ofusewhich itbelieves cannot inreality be
attained. TheInquiry Committee isoftheopinion thatuseofthenatural/nature-identical
hormones carries theriskofinexperienced application, incorrect dosage and
unsupervised injection which could posearisktotheanimal andtheconsumer. The
Inquiry Committee alsonotes thatresidual doubts withregard tolong-term cumulative
andinteractive potential carcinogenicity remain .Inaddition, theInquiry Committee
believes thatproven necessity andsocio-economic desirability should becriteria of
acceptability fortheuseof(bio)chemical growth promoters inanimal-rearing;
(d) theInquiry Committee doesnotaccept theargument thatprohibiting theuseforgrowth-
promotionsubstancestothedetrimentoftheconsumer,giventhatsubstancesarealready
incirculation which aremoreeffective inpromoting weight-gain andthatablack market
exists eveninauthorized pharmaceutical substances. TheInquiry Committee therefore
believes thatprotection ofpublic health isbestachieved byatotalban;
31"Opinion ontheproposal foraCouncil Directive amending Directive 81/602/EEC concerning theprohibition ofcertain
substances having ahormonal action andofanysubstances having athyrostatic action," ECOfficial Journal (C44),
15February 1985, p.14.
32Seepoint E.ofParliament 'sResolution, ECOfficial Journal, No.288, 11November 1985, p.15.
33Seepara. 2.31.WT/DS48/R/CAN
Page20
(e) theInquiry Committee notes thatgreat pressure touseillegal growth-promoting
substances exists inthecontext ofcontract fattening onintegrated farms andin
undertakings established bytheprocessing industry andistherefore oftheopinion that
legislation should beintroduced tostrengthen theindividual status andresponsibilities
ofsuchundertakings" (pages 5-6)(emphasis added ).
4.20 TheEuropean Communities added thattheEuropean Parliament hadadopted another important
report ontheissue ofuseofhormones foranimal growth promotion, the"Collins Report" of
7February1989.34Thisreportnotedthatthelicensingsystemsfortheregulationofveterinarymedicines
required thatanewproduct satisfy threecriteria: safety, quality andefficacy. However, thesecriteria,
which might besatisfactory fortherapeutic drugs, werenotsufficient forgrowth promotion products.
TheCollins Report proposed thattheECveterinary medicine licensing system beadapted toinclude
a"fourth hurdle", entailing anobjective socioeconomic andenvironmental impact assessment. Itargued
thatthesocial, agricultural andenvironmental implications oftheuseofgrowth andyield promoting
pharmaceuticals required alicensing system different fromthatwhich existed forthese products when
usedfortherapeutic purposes. Thesame report alsofound, interalia,that: "...Whereas theuseof
growth promotion hormones raises questions notonlyofpublic butalsoofanimal health; ...Whereas
theCommunity hasadutytoprotect thehealth anddefend theinterests ofitsconsumers andthefarm
animals; ...Whereas theCommunity isopposed toalldownward harmonisation ofhealth andhygiene
standards withregard totheproduction andmarketing offoodstuffs intheEuropean Community and
alsoatinternational level".
4.21 TheEuropean Communities rejected Canada 'scriticism ofthe1995ECScientific Conference.
Thecomments bySirJohnMaddox should bereadinthelightofhisconclusions asChairman ofthe
Steering Committee which organized theconference andtheletter hehadsenttoECCommissioner
Fischler, inwhich hestated:
"Ihavemyself beenimpressed thatnosingle classofgrowth promoters isatpresent sufficiently
wellunderstood forpeople tobeconfident thattheyknow themechanism bywhich effects
(andside-effects)areproduced.Whilethatstateofaffairspersists,risk-assessmentwillinevitably
remain hesitant, regulation cautious andpublic opinion suspicious ..."
4.22 Asfarasthecomments bytheCanadian scientists wereconcerned, theEuropean Communities
noted thatthe1995 ECScientific Conference wasfunded bytheECCommission butorganized by
anindependent steering committee. TheECCommission hadnotinterfered inthedesign ofthe
programme ornomination ofparticipants. Scientists employed by,orlinked to,thepharmaceutical
industry hadnotbeenexcluded andoneofthem wasaworkshop chairman. Thesteering committee
hadbeenasked toinvite those persons whom theyconsidered would beabletocontribute scientific
expertise onthesubject, regardless ofnational origin. Furthermore, contrary towhatwasstated in
theCanadian letter, noexpertise orinformation wasexcluded. Thesteering committee hadmade every
effort toobtain allrelevant information, forexample byannouncing ininternational journals the
possibilities fornon-participating scientists tocontribute tothedebate. Finally, the
European Communities rejected thesuggestions thatpersons other thanscientists should nothavebeen
invited toparticipate intheConference. Itwasamatter offactthattheuseofgrowth promoting
hormones wasamatter ofconcern andcontroversy andtheECCommission believed thatitwasright
toconsult policy makers andconsumers aswidely aspossible onissues suchasthis.
34European Parliament, Committee ontheEnvironment, Public Health andConsumer Protection, Report on"The USA's
Refusal tocomply withECLegislation onSlaughterhouses andHormones andtheConsequences ofthisRefusal", EP128
381/B, 7February 1989, named after itsreporter Mr.Collins, MEP.WT/DS48/R/CAN
Page21
(a) Article 1.1oftheSPSAgreement
4.23 Canada recalled thatArticle 1provided, inpart: "[t]his Agreement applies toallsanitary
andphytosanitary measures which may, directly orindirectly, affect international trade". TheEC
measures hadaprofound anddirect effect onCanadian beefexports totheEuropean Communities.35
Theissuewaswhether theECmeasures weresanitary measures within theterms oftheSPSAgreement.
Recalling thatAnnex AoftheSPSAgreement defined asanitary orphytosanitary measure tomean,
inpart,anymeasure applied "...toprotect human oranimal lifeorhealth within theterritory ofthe
Member fromrisksarising fromadditives, contaminants, toxins ordisease-carrying organisms infoods,
beverages orfeedstuffs", Canada noted thatcontaminants included veterinary drugresidues.
4.24 Canada claimed thatduring WTO consultations, theEuropean Communities hadnotclearly
indicated whether themeasures atissueweresanitary measures within thescope oftheSPSAgreement
ortechnical regulations within thescope oftheTBTAgreement. However, theEuropean Communities
hadsuggested thatthelegislator 'sintent could befound inthepreambles totheDirectives. The
preambles toDirective 81/602/EEC36andDirective 88/146/EEC37suggested thatonepurpose ofthe
measures wastoaddress aconcern forhuman health arising from thepresence ofhormone residues
inmeat. Onthisbasis, Canada submitted thattheECmeasures weresubject tothedisciplines ofthe
SPSAgreement.
4.25 TheEuropean Communities agreed withCanada thatthemeasures challenged were better
defined asmeasures falling within thescope oftheSPSAgreement rather thantheTBTAgreement.
TheEuropeanCommunitiesnotedthatanessentiallinkoftheSPSdisciplineswiththeregulatoryfreedom
oftheparties wasthatthemeasures applied were ofconcern totheSPSAgreement (andtheWTO
system) onlyiftheyaffected international trade.
35Seepara. 4.28.
36Thepreamble toDirective 81/602/EEC states, inpart:
"Whereas, duetotheresidues thattheyleave inmeat, certain substances withathyrostatic, oestrogenic, androgenic
orgestagenic action maybedangerous forconsumers; whereas these substances mayalsoaffect thequality ofmeat;
"Whereas, moreover, theharmless orharmful effects oftheuseofoestradiol-17 ,Progesterone, testosterone,
trenbolone andzeranol stillhave tobeexamined indetail; whereas, pending theadoption ofadecision relating
tothese substances, thecurrent measures governing them should bemaintained asaprecautionary measure with
dueregard forthegeneral provisions oftheTreaty."
37Thepreamble toDirective 88/146/EEC states, inpart:
"Whereas theadministration tofarmanimals ofcertain substances having ahormonal action isatpresent regulated
indifferent ways inthemember States; whereas while theirimmediate effect onanimals from thefarmer 'spoint
ofviewisclear, assessments oftheireffect onhuman health varyandthisisreflected intheregulations governing
theiruse;whereas thisdivergence distorts theconditions ofcompetition inproducts thatarethesubject ofcommon
market organizations andisaserious barrier tointra-Community trade.
...
"Whereas these distortions ofcompetition andbarriers totrade must therefore beremoved byensuring thatall
consumers areabletobuytheproducts inquestion under largely identical conditions ofsupply andthatthese products
correspond totheiranxieties andexpectations inthebestpossible manner; whereas suchacourse ofaction isbound
tobring about anincrease inconsumption oftheproduct inquestion...."WT/DS48/R/CAN
Page22
(b) Article 2.1oftheSPSAgreement
4.26 Canada argued thatArticle 2.1setoutalimited righttotakesanitary orphytosanitary measures:
"Membershavetherighttotakesanitaryandphytosanitarymeasuresnecessaryfortheprotection
ofhuman, animal orplantlifeorhealth, provided thatsuchmeasures arenotinconsistent with
theprovisions ofthisAgreement."
Canada claimed thatsince theECmeasures wereinconsistent withArticles 2,3,and5,theEuropean
Communities hadclearly exceeded thislimited right.
4.27 Canada noted thataresolution oftheEuropean Parliament, anopinion oftheEconomic and
SocialCommittee,andtheDirectivesthemselves,ascribedseveraladditionalpurposestotheECmeasures
which werenotcontemplated orsanctioned bytheSPSAgreement, suchasharmonizing theregulatory
schemes oftheECmember States andthereby removing competitive distortions andbarriers tointra-
Community trade, meeting consumer anxieties andexpectations, andbringing about anincrease in
theconsumption ofmeat products (seeparagraph 4.6). Aconsequence ofthese additional motives
wasthattheECmeasures weremore trade restrictive thannecessary toprotect human lifeandhealth.
4.28 Canada argued thatinparticular withrespect totheobjective ofencouraging intra-Community
trade, theECmeasures hadproven successful.38Theprice ofthissuccess, however, hadbeenpaid
byexporters suchasCanada, whowereeffectively eliminated from theECmarket asaresult ofthe
ECmeasures withrespect tohormones, asshown bythefollowing quantities inmetric tons: 1984:
5,664; 1985: 4,853; 1986: 4,696; 1987: 3,836; 1988: 2,339; 1989: 648; 1990: 383; 1991:
162; 1992: 479; 1993: 223; 1994: 537; 1995: 287. Asadirect result oftheimplementation
ofsuchmeasures inJanuary 1989, Canada 'sexports intotheECmarket hadsuffered a72percent
decline.39Thiswasfrom alevelthathadalready beenseverely impaired bytheimplementation of
theThird Country Meat Directive in1987, asaresult ofwhich theEuropean Communities had
unilaterally abandoned thehitherto accepted practice ofmutual recognition ofnational standards and
hadinsisted thatallECtrading partners comply withECstandards. TheECmeasures atissue and
theThird Country Meat Directive had,moreover, bothbeen applied more stringently andmore
precipitately tothirdcountries thantoECmember States.40
4.29 InthecaseoftheECmeasures atissue, thirdcountries hadtomeettheECmeasures orcease
exports intotheEuropean Communities. Internally, however, abuses hadcontinued sincethemeasures
hadentered intoforce. Consumer anxieties, farfrombeing addressed bytheECmeasures, hadbeen
38Canada claimed thattheproduction- andexport-related measures taken under theCAP, theThird Country Directive
andtheECmeasures atissue allcombined toencourage intra-Community trade andboost extra-EC exports, while effectively
blocking market access forexporting countries such asCanada.
39Canada noted that,based onafive-year average, thenumber oftreated animals inCanada wasapproximately 76.8 per
centofthose entering thefoodchain, andthenumber ofuntreated animals was23.2 percent. However, thepercentage
ofexported meat andmeat products thatoriginated from treated animals would have differed from those figures because
meatfrom treated steers andheifers isofhigher quality thanmeatfrom untreated bullsanddairy cows, andCanada 'sexports
ofbeefunder theHilton BeefQuota andoffalforhuman consumption would have beenconstituted, inlarge part, bymeat
from treated animals.
40Canada explained thattheECThird Country Meat Directive required countries exporting totheEuropean Communities
tocomply fully withECstandards. Incontrast, Canada andmany other countries required anexporting country tomeet
equivalent,albeitnotnecessarilyidentical,standards.AccordingtoCanada,theDirectivewasappliedtothirdcountryexporters
sooner thantotheECmember States. InthecaseofCanada, theDirective waseffective 1986, when afirstlistof
establishments eligible toexport under theECDirective hadbeen drawn up.Even aslateas1991, however, most ofthe
Mediterranean ECmember States, aswellasFrance, hadnotbeen forced tocomply withthestandards oftheDirective.WT/DS48/R/CAN
Page23
exacerbated bypersistent reports ofillegal useofprohibited substances andtheECmeasures hadfailed
toincrease consumption.
4.30 Canada claimed thatamajor problem confronting theEuropean Communities hadbeenan
imbalance inproduction versus consumption. According toaspecial report produced bytheECCourt
ofAuditors:
"Alookatthetrend inconsumption andproduction since 1980 reveals thatCommunity
production, which, admittedly, iscyclical, hasalways, evenatthelowest point ofthecycle,
exceededconsumption.Thisstructuralimbalance,whichhaspersistedoveradecade,isgrowing
worse. Thesurplus needing tobedisposed ofevery yearontheworld market has,overthe
pasttenyears, represented onaverage about 6percentofCommunity production, which is
tending togrow atslightly lessthan0,5percentayear."41
4.31 In1992, theEuropean Communities hadundertaken toaddress some ofthese problems by
launching areform oftheCAP. Even so,theCourt ofAuditors hadopined that,inthebeefandveal
sector, "[i]nthelongterm, thestructural surpluses willcontinue tobeaproblem, onewhich the1992
CAPreform hasfailed toremedy intheslightest andwhose extent ishardly likely todiminish either,
unless corrective measures ...areimplemented".42
4.32 Canada concluded thatinthecontext ofpersistent over-production anddeclining consumption,
there hadbeenscant incentive within theEuropean Communities toaddress thetrade concerns ofits
trading partners. Theimpairment toCanada 'strademustbeassessed notonlyagainst theactual losses
ithadsuffered asaresult oftheECmeasures, butagainst itsincreasing export potential, asevidenced
byCanada 'stotalexports since the1980s.
4.33 TheEuropeanCommunitiesrejectedCanada'sargumentthattheECmeasureshadbeenadopted
inorder toprotect production from foreign competition. Thereference tothedivergence inthe
legislation oftheECmember States which distorted theconditions ofcompetition andaffected free
circulation ofproducts inintra-EC trade(1stand2ndparagraphs ofDirective 88/146/EEC), wasmade
forthesolepurpose ofjustifying theneedtotakeaction attheEClevel. Because ofitsinternal
constitutional structure, theEuropean Communities wasobliged totakeaction inorder toeliminate
distortions intheconditions ofcompetition andtoincrease freeintra-EC trade.43Thepreamble of
theDirective thusclearly explained thattheunderlying objective wastorespond inaharmonized way
totheeffect ofthesehormones onhuman health. Thisobjective, however, wasnotinitselfindependent
ormore important thantheobjective ofsafeguarding against riskstohuman andanimal health resulting
from thesubstances atissue. These firstthree paragraphs ofthepreamble oftheDirective clearly
indicated these objectives:
"Whereas theadministration tofarmanimals ofcertain substances having ahormonal action
isatpresent regulated indifferent ways inthemember States; whereas while theirimmediate
effect onanimals fromthefarmer 'spoint ofviewisclear, assessments oftheireffect onhuman
health varyandthisisreflected intheregulations governing theiruse;whereas thisdivergence
41Court ofAuditors, Special Report No3/94ontheimplementation oftheintervention measures provided forbythe
organization ofthemarket inbeefandveal, together withthecommission 'sreplies, (1994), ECOfficial Journal (C356)
1,p.11.
42Ibid.,p.18.
43TheEuropean Communities indicated thatthisobligation resulted from Articles 100and100A, inconjunction inthis
casewithArticles 30and36ofECTreaty.WT/DS48/R/CAN
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distorts theconditions ofcompetition inproducts thatarethesubject ofcommon market
organizations andisaserious barrier tointra-Community trade;
"Whereas theuseofhormonal substances forfattening purposes should therefore beprohibited;
whereas theuseofcertain substances fortherapeutic purposes maybeauthorized butmust
bestrictly controlled inorder toprevent anymisuse ofthem."
4.34 TheEuropean Communities further argued thataction attheEClevelwasexplicitly permitted
byArticle XXIV:8(a) ofGATT. Itsubmitted thatwhen theEuropean Court ofJustice examined the
object andpurpose ofDirective 85/649/EEC (invalidated onprocedural grounds andsubsequently re-
enacted inDirective 88/146/EEC) ithadnoted that"theaimofthedirective, according totherecitals
initspreamble, istoprotect human health andconsumer interests withaview toeliminating the
distortion ofconditions ofcompetition andbringing about anincrease inconsumption oftheproduct
inquestion" (emphasis added). Theessential aimoftheDirective, therefore, wasfound tobethe
protection ofhuman health andofconsumer interests. Thisprotection waspursued withaviewto
improving thequality ofmeatthrough regulating theconditions fortheproduction andmarketing of
meat. Thisobjective, which wasexpected toincrease consumption oftheproducts, came within the
objective oftheCommon Agricultural Policy. Thisjustified action atEClevel.
4.35 Furthermore,theEuropeanCommunitiesassertedthatthehistoricalrecordclearlydemonstrated
thatthepurpose oftheECmeasures wastoprotect human andanimal health fromrisksarising from
theuseofthehormones atissueforanimal growth promotion. TheEuropean Communities noted that
theEuropean Parliament hadproposed abanonimports ofmeat from animals treated withgrowth
promotinghormonesprimarilybecause"scientificinformationaboutthesesubstancesisfarfromcomplete
andthatconsiderable doubt therefore exists about thedesirability oftheiruseandoftheireffect on
human health".44Serious health concerns hadbeenclearly stated indifferent MEP reports, including
the"Nielsen Report", the"Pimenta Report" andthe"Collins Report", andtheEuropean Parliament
aswellastheEconomic andSocial Committee, hadremained constantly opposed totheauthorization
ofallthesehormones foranimal growth promoting purposes forreasons ofpossible hazards tohuman
andanimal health.
4.36 TheEuropean Communities rejected Canada 'sreference totheso-called ECthird-country meat
Directive which itconsidered tobeirrelevant tothiscase. IfCanada hadanyproblems withthe
conformity ofthisDirective withtheinternational obligations oftheEuropean Communities, itcould
ofcourse complain toGATT andtheWTO, butithadnotdoneso.Theincrease intheECintervention
stocks ofbeefwasunrelated totheobjective andpurpose ofthechallenged measures, because such
highintervention stocks ofbeefdidnotexistintheECmember States thatintroduced theprohibition
ontheuseofthese hormones asearly as1961; suchhighintervention stocks ofbeefdidnotexist
in1981 when thisprohibition wasforthefirsttimeimposed atEClevel; andsuchhighintervention
stocks ofbeefdidnotexistinApril 1996when theEuropean Communities adopted Directive 96/22/EC
which re-enforced theprohibition ontheuseofthese hormones. TheEuropean Communities further
submitted thatthefactthattheDirective offered equal access totheECmarket forthird-country meat
wasadditional proof thatthere wasnoprotectionist purpose intheECmeasures. Statistics showed
thattheEuropean Communities hadcontinued toimport about thesame quantities ofmeatasbefore
theapplication oftheban,itwas,however, meatfromanimals towhich hormones forgrowth promotion
purposes hadnotbeenadministered. ThefactthattheCourt ofAuditors 'report found structural
surpluses intheCommon Agricultural Policy oftheEuropean Communities wasnothing new.
4.37 TheEuropean Communities argued thattheEClegislation inquestion didnotimpose aban
onCanadian meatoronmeatfrom anyother origin (i.e.itwasorigin neutral). Canada continued
44Point EofParliament 'sResolution, ECOfficial Journal, No.288, 11November 1985, p.158.WT/DS48/R/CAN
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toexport freshmeatnotdestined forhuman consumption. Canada alsoexported totheEChormone-free
meatproducts forhuman consumption onthebasis ofamutually agreed arrangement. Furthermore,
asregarded illegal use,theEuropean Communities didnotseewhatrelevance thisargument hadto
thecasebefore thePanel. Canada wasusing theargument, sometimes usedinfavour oflegalising
ordecriminalising theuseofnarcotic drugs byhumans, totheeffect thatlegalising some drugs
discouraged theuseofothers. Whether ornotthiswasthecasewasopen todebate butitwasnot
relevant tothepresent dispute. Inanycase, theEuropean Communities wastaking veryseriously the
situation asregarded potential illegal useofthese substances foranimal growth promotion. Thiswas
evidenced from thestricter provisions ondetection, control andillegal useapplied intheEuropean
Communities. Furthermore, Directive 96/23/EC tightened upcontrols andincreased substantially the
sanctions andpenalties tobeapplied topersons found toactcontrary totheprovisions ofEClaw.
4.38 TheEuropean Communities alsonoted thatthere wereseveral countries which didnotallow
theuseofanyormostofthesehormones foranimal growth promotion, butsome ofthemdidnotimpose
anyrestrictions onimports ofhormone-treated meatbecause theyhardly imported anymeatastheir
domestic production sufficed tocover demand. Argentina, forinstance, didnotallow theuseofthe
three natural hormones forgrowth promotion (because residues ofthese hormones could noteasily
bedetected), butdidnotapply aprohibition onimports ofanimals ormeattreated withthese three
hormones asthere were virtually noimports taking place. Incontrast, theEuropean Communities
hadalways imported large quantities ofmeatandhadtoadopt themeasures inquestion inorder to
ensure thattheobjectives ofitsdomestic sanitary policy werenotcircumvented through imports from
thirdcountries.
4.39 TheEuropean Communities argued thatitsmeasures offered equal opportunities ofaccess to
theECmarket forallthird-country animals andmeatfrom animals towhich nohormones hadbeen
administered forgrowth promotion purposes. Ofthe31countries which were authorized toexport
meattotheEuropean Communities, onlysixapparently allowed theuseofsome orallofthesehormones
forgrowth promotion purposes. Allofthese 31countries (including Canada) hadcontinued toexport
totheEuropean Communities animals andmeat from animals towhich nohormones hadbeen
administered forgrowth promotion purposes. Thus, overall thesame competitive pressure asbefore
wasmaintained from third-country imports ondomestic meat production. Theintention oftheEC
measures atissue, therefore, wasnottoshield domestic meatproduction from foreign competition.
TheEClegislation diddistinguish between countries which permitted theuseofhormones forgrowth
promotion andthose which didnot,butthiswasajustified distinction inviewoftheECchosen level
ofprotection, andtheargument thatitsmeasures were adisguised restriction ontrade, was
unsubstantiated.
4.40 According totheEuropean Communities, theCanadian exports offresh andfrozen meat(to
theEuropean Communities) fortheyears 1985 to1995 were asfollows: 1985: 312tonnes, 1986:
571tonnes, 1987: 457tonnes, 1988: 28tonnes, 1989: 7tonnes, 1990: 87tonnes, 1991: 106tonnes,
1992: 25tonnes, 1993: 40tonnes, 1994: 53tonnes, 1995: 58tonnes.45
(c) Article 2.2oftheSPSAgreement
4.41 Canada noted thattheSPSAgreement indicated the"Basic Rights" ofMembers inArticles 2.1
and2.4,andthe"Basic Obligations" inArticles 2.2and2.3. Article 2.2setoutthree conditions:
"Members shallensure thatanysanitary orphytosanitary measure isapplied onlytotheextent
necessary toprotect human, animal orplantlifeorhealth, isbased onscientific principles and
45TheEuropean Communities indicated thatthese figures were based onEurostat statistics. Thefigures provided by
Canada included offal.WT/DS48/R/CAN
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isnotmaintained without sufficient scientific evidence, except asprovided forinparagraph 7
ofArticle 5."
4.42 Canada maintained theECmeasures wereapplied wellbeyond theextent deemed necessary
bytheEuropean Communities toprotect human lifeandhealth from comparable risks posed by
antimicrobial growth promoters infeedadditives, andthedemonstrably greater risksposed bysome
veterinary drugs usedfortherapeutic purposes. Consequently, theECmeasures werenotapplied only
totheextent necessary toprotect human lifeorhealth. Inaddition, theECmeasures weremaintained
without sufficient scientific evidence, since study afterstudy hadconfirmed thatthesixhormones in
question weresafeforuseingrowth promotion (seeparagraph 4.134). Consequently, Canada claimed
thattheECmeasures were contrary toArticle 2.2.
4.43 TheEuropean Communities noted thatArticle 2.2required thatsanitary orphytosanitary
measures mustbebased onscientific principles, asopposed tonon-scientific ones, suchassuperstition.
Ifameasure wasaimed atreducing oreliminating arisktohealth, thenitmustactually address that
riskinamanner which could bescientifically justified. Canada hadnotshown thatthemeasures
complained against werenotbased onscientific principles. Alogical consequence oftherequirement
formeasures tobebased onscientific principles wasthattheymustnotbemaintained without scientific
evidence .TheEuropean Communities claimed thatallMembers hadmeasures inplace before the
SPSAgreement wasdrawn up,andintheabsence ofthisrequirement itcould havebeenargued that
therequirement forbasing measures onscientific principles could notbeapplied retrospectively.
4.44 TheEuropean Communities noted thattheSPSAgreement hadnotdefined theterm"scientific
evidence" sinceitscontent wasrelative interms oftimeandwasdependent ontheprinciples, methods,
experiments anddataused. What might beanacceptable scientific method foronescientist might
notsatisfy another, whomight bemore interested incertain other scientific principles oraspects totally
neglected orpartially examined bythefirstscientist. Forthatreason theSPSonlyrequired "sufficient",
notclearorcertain, scientific evidence.46Theterm"sufficient" wasalsonowhere defined intheSPS
Agreement. TheEuropean Communities argued thatitwasgenerally agreed thatsufficient could not
mean other thantheminimal levelofscientific evidence required.
4.45 TheEuropean Communities noted thattheSPSAgreement alsorequired Members, intheir
riskassessment, totakeintoaccount "available scientific evidence" andargued thatfromthe"available"
scientific evidence, aMember wasentitled torelyonthatwhich itsownscientists saidwasappropriate
andsufficient anddisregard other available evidence. Itfollowed thatneither thePanel noranyother
Member might judge theadequacy ofthescientific evidence uponwhich aMember based itsmeasure
inorder toachieve itslevelofsanitary orphytosanitary protection47.Forthesame reasons, aCodex
group ofscientific experts could notjudge theadequacy ofthescientific evidence usedbyaMember.48
46TheEuropean Communities argued thattheterm"scientific evidence" hadadifferent meaning from therequirement
toprovide "evidence" inalegal trial.
47TheEuropean Communities noted thatthishadbeenexplained intheUSStatement ofAdministrative Action asfollows:
"Itisclear thattherequirement intheSPSAgreement thatmeasures bebased onscientific principles andnotbemaintained
"without sufficient scientific evidence" would notauthorize adispute settlement panel tosubstitute itsscientific judgment
forthatofthegovernment maintaining thesanitary orphytosanitary measure. Forexample, byrequiring measures tobe
based onscientific principles (rather than, forinstance, requiring measures tobebased onthe"best" science) andnotto
bemaintained without sufficient scientific evidence (rather than, forinstance, requiring anexamination ofthe"weight of
evidence"), theSPSAgreement recognizes thefactthatscientific certainty israreandmany scientific determinations require
judgmentsbetweendifferingscientificviews.TheSPSAgreementpreservestheabilityofgovernmentstomakesuchjudgments"
(atpage 90,emphasis intheoriginal).
48Insupport ofitsargument, theEuropean Communities cited anarticle byD.A. Wirth (1994), "The Role ofScience
intheUruguayRoundandtheNAFTATradeDisciplines,"Vol.27CornellInternationalLawJournal,pp.817-859,pp.856-57.WT/DS48/R/CAN
Page27
Inother words, ifthe"weight" ofavailable scientific evidence indicated thatasubstance wasnot
dangerous tohuman health, butanother partofavailable scientific evidence indicated thattheremight
bepotential hazards tohuman oranimal health, aMember wasentitled under theSPSAgreement to
takeaprecautionary approach andbaseitsmeasure onthelatterpartoftheavailable scientific evidence.
Itwassufficient ifthegovernment maintaining themeasure hadascientific basis forit.However,
theEuropean Communities stressed thatthisdidnotmean thatMembers wereobliged todemonstrate
ascientifically confirmed adverse effect from aparticular hazard before theymight takemeasures.49
TheSPSAgreement could nothavebeenintended tooperate insuchawaythatMembers mustwait
untilpeople were actually sickordying before being allowed totakemeasures.
4.46 TheEuropeanCommunitiesnotedthattheclosesttheSPSAgreementcametodefiningsufficient
"scientific evidence" wasinthefootnote toArticle 3.3,where theconcept ofa"scientific justification"
wasdefined asfollows:
"Forthepurposes ofparagraph 3ofArticle 3,thereisascientific justification if,onthebasis
ofanexamination andevaluation ofavailable scientific information inconformity withthe
relevant provisions ofthisAgreement, aMember determines thattherelevant international
standards, guidelines orrecommendations arenotsufficient toachieve itsappropriate level
ofsanitary orphytosanitary protection."
Itfollowed thatscientific justification required anexamination andevaluation ofavailable scientific
information, based onscientific principles. However, attheenditwasstilltheprerogative ofthe
Member inquestion todecide whether theinternational standard, guideline orrecommendation was
sufficient toachieve itsappropriate levelofsanitary protection. Thelevelofprotection wasdecided
bytheMember alone anditwasnotajudgment thatmustbebased onscientific principles orscientific
evidence.
4.47 Canada rejected theECinterpretation ofArticle 2.2,that"...neither thePanel noranyother
Member oftheSPSAgreement mayjudge theadequacy ofthescientific evidence uponwhich aMember
based itsmeasure inorder toachieve itslevel ofsanitary orphytosanitary protection", asitwould
render theobligation inArticle 2.2anullity, andviolate theprinciple ofeffectiveness. "Sufficient
scientific evidence" wasnotanempty requirement. Itsetathreshold thatrequired more thandeficient
orscanty evidence. Ifthelevelofscientific evidence wasinsufficient, thenaMember wasentitled
toadopt aprovisional measure under Article 5.7. Canada noted thattheEuropean Community had
stated thatitsmeasures were notprovisional measures, soArticle 5.7didnotprovide anexception
totheEC'sobligation under Article 2.2.
4.48 Canada agreed withandadopted theargument advanced byAustralia thatArticle 11.2ofthe
SPSAgreement explicitly acknowledged thatdisputes mayinvolve scientific ortechnical issues. In
Canada 'sview, panels mustbeabletoseekexpert advice onthese issues when itmayberelevant to
examiningwhetheraMemberhascompliedwithitslegalobligations.Indeed,theEuropeanCommunities
hadsuggested thatsuchadvice should besought intherelated US-EC Panel50,andtheexperts chosen
toassist inthatcasewould alsobeproviding advice tothisPanel.
4.49 Canada submitted thattheECmeasures weremaintained without sufficient scientific evidence,
andwere, therefore, inconsistent withArticle 2.2.
49TheEuropean Communities noted that,forexample, ithadbeenrecently reported thatitwasonlynowthatscientists
haddiscovered themechanism bywhich smoking could cause cancer. Butgovernments allovertheworld hadlongago
been taking measures toprevent orreduce smoking.
50US-EC Measures Concerning Meat andMeat Products (Hormones), WT/DS26/7.WT/DS48/R/CAN
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4.50 TheEuropean Communities argued thatinthePanel proceedings anumber ofscientists had
explainedtheirviewsonthepotentialdangerstohumanandanimalhealthfromtheuseofthesehormones
forgrowth promotion. However, noneofthescientific experts advising thePanel hadsaidthatthe
experts advising theEuropean Communities didnotemploy scientific principles intheirresearch.
Article 2.2oftheSPSAgreement didnotrequire thebestscience northeweight ofscientific evidence
tobetaken intoaccount; itonlystipulated thatthere should be"scientific principles" and"sufficient"
(notabsolute) scientific evidence. Forexample, Dr.Lucier hadagreed withtheconclusions ofthe
ECscientists thatboththenatural andsynthetic hormones werecarcinogenic atlowlevels (thenatural
hormones arecarcinogenic evenatexisting physiological levels). Some ofthescientists whoattended
themeetings ofthePanel (andthose ofJECFA 1988) might notagree withtheconclusions ofthe
scientists advising theEuropean Communities, butthiswasnotrelevant forthepurposes ofArticles 5.2,
2.2and3.3oftheSPSAgreement. What wasimportant waswhether, inthescientific research employed
bytheECscientists (orthescientific reports towhich theymade reference intheirreports), theminimal
attributes ofscientific inquiry wererespected. TheEuropean Communities hadnotheard theopposite
fromanyoftheexperts advising thePanel norfromCanada. Therefore, theEuropean Communities
wasallowed totakeintoaccount itsscientific views (ortheviews ofthescientists towhich itreferred)
initsassessment oftherisksofthese hormones forgrowth promotion.
4.51 TheEuropean Communities noted thatthescientific principles onwhich the1988 JECFA
Report wasbased might alsobesaidtobealsopartofavailable scientific evidence. Butitwasnot
necessarily thebestnortheprevailing one. TheEuropean Communities wasentitled tofollow the
otherpartofscientific evidence which showed thatthesehormones weredangerous tohuman andanimal
health when usedforgrowth promotion.
(d) Article 2.3oftheSPSAgreement
4.52 Canada observed thatArticle 2.3wasbased ontherequirements ofthechapeau ofArticle XX
ofGATT, clarifying thatthepoint ofcomparison for"where identical orsimilar conditions prevail"
included theterritory oftheMember taking themeasure. Article 2.3readasfollows:
"Members shallensure thattheirsanitary andphytosanitary measures donotarbitrarily or
unjustifiably discriminate between Members where identical orsimilar conditions prevail,
including between theirownterritory andthatofother Members. Sanitary andphytosanitary
measures shallnotbeapplied inamanner which would constitute adisguised restriction on
international trade."
4.53 Canada argued thatinReformulated Gasoline ,51theAppellate Body hadreviewed thechapeau
toGATT Article XX.Stressing thecloserelationship between thetextofthechapeau andtheobligation
inArticle 2.3,Canada submitted thattheAppellate Body'sinterpretation oftherequirement thata
measure shall "...notbeapplied inamanner which would constitute adisguised restriction on
international trade ..."wasrelevant tothepresent case. TheAppellate Body hadfound:
"Arbitrary discrimination", "unjustifiable discrimination" and"disguised restriction" on
international trademay,accordingly, bereadside-by-side; theyimpart meaning tooneanother.
Itiscleartousthat"disguised restriction" includes disguised discrimination ininternational
trade. Itisequally clear thatconcealed orunannounced restriction ordiscrimination in
international trade doesnotexhaust themeaning of"disguised restriction". Weconsider that
"disguised restriction", whatever elseitcovers, mayproperly bereadasembracing restrictions
amounting toarbitrary orunjustifiable discrimination ininternational trade taken under the
guise ofameasure formally within theterms ofanexception inArticle XX.Putinasomewhat
51WT/DS2/AB/R, adopted 20May 1996.WT/DS48/R/CAN
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different manner, thekinds ofconsiderations pertinent indeciding whether theapplication of
aparticular measure amounts to"arbitrary orunjustifiable discrimination", mayalsobetaken
intoaccount indetermining thepresence ofa"disguised restriction" oninternational trade.
Thefundamental theme istobefound inthepurpose andobject ofavoiding abuse orillegitimate
useoftheexceptions tosubstantive rules available inArticle XX."52
4.54 Canada claimed thatapplying thistothepresent case, aprotectionist measure intheguise of
asanitary measure formally within theterms oftheSPSAgreement wastheessence ofadisguised
restriction oninternational trade. Oneindication thatameasure hadbeentaken forapurpose other
thanthepurpose stated wasthatthemeasure wasmore restrictive thannecessary. Inthepresent case,
theECmeasures hadbeenshown tobefarmore restrictive thannecessary toachieve thelevel of
protection achieved bycomparable controls overtheuseofantimicrobial growth promoters andother
veterinary drugs. Thiswasnotsurprising because, asCanada hadpreviously indicated, therelevant
Directives, Resolution oftheEuropean Parliament andopinion oftheEconomic andSocial Committee
demonstratedthattherewereseveraladditionalpurposestotheECmeasureswhichwerenotcontemplated
orsanctioned bytheSPSAgreement (seeparagraph 4.27).
4.55 Canada claimed thatinharmonizing theirregulations onthemostrestrictive ECmember State
regulations, theEuropean Communities hadvirtually eliminated allimports ofbeeffrom countries
thatpermitted theuseofgrowth promoting hormones, suchasCanada (seeparagraph 4.28). Canada
submittedthattheECmeasuresweremorerestrictivethannecessarytomeetalegitimateSPSAgreement
objective, namely toprotect human lifeorhealth. TheECmeasures were applied inamanner that
controlled domestic production andeffectively limited foreign competition, constituting adisguised
restriction oninternational trade.
4.56 TheEuropeanCommunitiesarguedthatmanydifferentkindsofbiological,chemicalorphysical
hazards might occur infoods, andgovernments hadtodecide towhat degree theyaimed toprotect
theirpopulations from these hazards. These decisions were taken, aswere anypolitical decisions,
inthelightofanumber offactors including thepotential danger tohealth andthecostandfeasibility
ofachieving effective protection. Forexample, inthecaseofafatally poisonous substance, orone
which caused averyserious orfatalcondition suchascancer, governments would generally setavery
highlevelofprotection, i.e.theyaimed toavoid thepresence ofsuchasubstance infoodaltogether.
However, inthecaseofalesser hazard, suchasanorganism which caused anuncomfortable, but
transient andnonlife-threatening effect, governments might setalevelofprotection which aimed to
minimize, butnotnecessarily eliminate, thepresence oftheorganism infood. TheEuropean
Communities stated thatitslevelofprotection inthiscasewasnoresidue ofthese hormones inmeat.
Thislevelresulted from theprovisions oftheECDirectives which prohibited theadministration to
farmanimals, byanymeans whatsoever, of"substances having athyrostatic action orsubstances having
anoestrogenic, androgenic orgestagenic action"; ortheslaughter orsaleofanyanimal towhich these
substances hadbeenadministered, orofthemeatormeatproducts from suchanimals. Theaimof
theseprovisions wastoprotect human andanimal health byseeking alevelofprotection which required
thepresence ofnoresidues inmeatfromanimals towhich these hormones hadbeenadministered for
growth promotion. TheEuropean Communities noted furthermore thatitsmeasure applied notonly
tothesixhormones indispute, buttoallhormones, substances andcombinations thereof which exerted
theabove-mentioned action onallfarmanimals (i.e.notonlyonbeefcattle). Inreply totheCanadian
argument thatthelevelofprotection inthecaseofthesehormones washigher thanthelevelofprotection
theEuropean Communities applied against antimicrobial feedadditives andtherefore thattheobjective
oftheECmeasures wastocontrol domestic production andeffectively limitforeign competition, the
European Communities indicated thatthere wasnothing inthetextofthecontested measures, the
legislative history orinother document tosuggest thatthepurpose forwhich themeasures hadbeen
52Ibid.,p.25.WT/DS48/R/CAN
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adopted wastoprotect ECproduction ofmeatfromforeign competition (paragraphs 2.1-2.5 andff.).
4.57 TheEuropean Communities argued thatthe"appropriate level" aMember decided toapply
initsterritory didnothavetobeexpressed inthesametechnical fashion, i.e.asanMRL. International
practice andtheSPSAgreement leftthischoice totheMember concerned asamatter ofpolicy. Thus,
aMember might decide instead ofimposing astricter MRL toprohibit altogether theuseofthesubstance
inthefirstplace, ifthiswastheonly"reasonably available alternative taking intoaccount technical
andeconomic feasibility thatachieves itsappropriate levelofsanitary orphytosanitary protection and
issignificantly lessrestrictive ontrade". TheEuropean Communities hadcontinued toimport about
thesame quantities ofmeat asitdidbefore theimplementation oftheban,withthedifference that
thiswasmeatfromanimals nottreated withgrowth promotion hormones. TheECmeasure didnot,
therefore,contraveneArticle2.3.TheEuropeanCommunitiesarguedthatCanadahadfailedtodischarge
itsburden ofproof inthiscase. Inparticular, ithadfailed toestablish that,inthefaceofthe
overwhelming scientific evidence thattheuseofhormones foranimal growth promotion waspotentially
verydangerous topublic andanimal health, therewereothertypeofmeasures which, whilst significantly
lessrestrictive ontrade, were capable ofensuring thatthelevel ofprotection which the
European Communities hadchosen inthiscase(noresidue ofhormones inanimals andmeat) could
beeffectively achieved. Conversely, theEuroperan Communities hadgonethrough thatexercise in
1984 andrecently inApril 1996 anddecided thattheprohibition onuseofthese hormones inanimal
growth promotion wastheonlymeasure reasonably available andlessrestrictive oftrade. The
European Communities noted thatinCanada theadministration oftheimplant atasiteother thanwhere
recommended wasnotlikely tobesufficient proof ofadulteration under theCanadian Food andDrugs
Act. TheCanadian Drugs Directorate recommended that"theliverandkidney ofanimals implanted
withthese drugs inareas other thantheearshallnotbepermitted forsaleasfood". Butasregarded
thecarcass oftheanimal, itrecommended onlythat"alltheareaofimplantation andanyadjacent areas
showing evidence ofinflammation aretobedestroyed". So,improper administration didnotresult
intherejection oftheentire carcass fromthefoodchain. Itwasonlywhen aninspector believed that
there hadbeenadministered products notlicensed foruseinCanada thattheentire carcass wastobe
taken outofthefoodchain. TheEuropean Communities argued thatnotonlywerethereobvious risks
tohuman health arising from thistypeofpolicy, butthere were practically nocontrols andchecks
forresidues ofthesehormones taking intoaccount theentire animal production destined forexportation
orforhuman consumption inCanada. TheFood andDrug Regulations ofCanada (section B.01.046
andB.01.047) didnotspecify thatfoodcontaining hormone residues wastobeconsidered "adulterated",
thussuchfoodcould besold. Alsosection B.01.048 thereof listed onlytwodrugs (chloramphenicol
anditssaltsandderivatives, anda5-nitrofuran compound) whose administration toanimals rendered
themandmeatthereof unsuitable forsale.These factsalone justified theprecautionary approach adopted
bytheEuropean Communities, itshowed thereasonable andproportional nature ofitsmeasures in
thelightoftherisksinvolved, andunderlined thefailure ofCanada toshow thatthere wasanother
typeofmeasure available totheEuropean Communities, equally effective andlessrestrictive ontrade.
(e) Article 2.4oftheSPSAgreement
4.58 Canada submitted thatArticle 2.4confirmed oneroleoftheSPSAgreement asanelaboration
oftherulesfortheapplication ofGATT which related totheuseofsanitary orphytosanitary measures,
andinparticular theprovisions ofArticle XX(b):
"Sanitary orphytosanitary measures which conform totherelevant provisions ofthisAgreement
shallbepresumed tobeinaccordance withtheobligations oftheMembers under theprovisions
ofGATT which relate totheuseofsanitary orphytosanitary measures, inparticular the
provisions ofArticle XX(b)."WT/DS48/R/CAN
Page31
4.59 Canada argued thatsince theECmeasures didnotconform totheprovisions oftheSPS
Agreement, theycould notbepresumed tobeinaccordance withtheprovisions ofGATT which related
totheuseofsanitary measures, andinparticular Article XX(b).
4.60 TheEuropean Communities argued thatunder Article 3.2,ifasanitary measure conformed
toarelevant international standard, guideline orrecommendation, itwasdeemed tobenecessary to
protect human, animal orplant lifeorhealth, anditwaspresumed tobeconsistent withtherelevant
provisions oftheSPSAgreement andGATT. However, thefactthatasanitary orphytosanitary measure
differed fromarelevant international standard, guideline orrecommendation didnot,initself, create
anyadverse presumption concerning thatmeasure. Thiswasallthemore thecasewhen there was
nosuchinternational standard (such asforMGA). TheEuropean Communities further argued that
thefactthatameasure inconformity withaCodex standard wasdeemed tobeconsistent withtheSPS
Agreement wasoneoftheweaknesses oftheSPSAgreement, given thatmany Codex standards,
guidelines andrecommendations wereoutofdate,having beenadopted decades before thedevelopment
ofsophisticated analytical methods.
(f) Article 3.1oftheSPSAgreement
4.61 Canada noted thatother provisions oftheSPSAgreement elaborated thebasic rights and
obligations setoutinArticle 2.Article 3detailed therights andobligations ofMembers withrespect
toharmonization. Article 3.1provided that:
"Toharmonize sanitary andphytosanitary measures onaswideabasisaspossible, Members
shallbasetheirsanitary orphytosanitary measures oninternational standards, guidelines or
recommendations, where theyexist, except asotherwise provided forinthisAgreement, and
inparticular inparagraph 3."
4.62 Forfoodsafety, thestandards, guidelines andrecommendations established bytheCodex
applied.53Inthepresent case, Codex hadadopted MRLs fortrenbolone andzeranol, buthadnotset
MRLs foroestradiol, testosterone andprogesterone because theestimated consumption ofthenatural
hormones waswellbelow anynumerical value thatwould ordinarily beassigned tothem.
4.63 Article 3.1compelled theEuropean Communities tobase itssanitary measures onthese
international standards, except asotherwise provided forintheSPSAgreement. Canada noted that
thedefinition of"base" (usually followed by"on"or"upon") wasto"found orestablish".54Asummary
oftheMRLs allocated bytheECCommittee onVeterinary Medicinal Products55acknowledged that
theECmeasures werebased onMRLs ofzeroforzeranol andtrenbolone, andwerenotbased onthe
Codex MRLs. Canada further observed thattocomply withRegulation 2377/90/EEC, theEuropean
Communities wasrequired todetermine whether MRLs werenecessary forthethreenatural hormones.
TheEuropean Communities haddetermined thatoestradiol-17 didnotrequire anMRL (Regulation
3059/94/EC) butdidnotappear tohaveyetdetermined whether MRLs werenecessary fortheother
twonatural hormones.
4.64 Canada claimed thatalthough MRLs were notsanitary measures inandofthemselves, full
acceptance oftheCodex MRLs forresidues ofveterinary drugs infooddictated thatdistribution of
53SPSAgreement, Annex A,para. 3(a).
54R.E. Allen, ed.,"The Concise Oxford Dictionary ofCurrent English", 8thed.,Oxford: Clarendon Press, pp.89-90.
55R.J.Heitzman, ed.,"Agriculture -Veterinary Drug Residues -Residues infood-producing animals andtheirproducts:
Reference materials andmethods" (Luxembourg: Office forOfficial Publications oftheEuropean Communities, 1992),
p.4.WT/DS48/R/CAN
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foodconforming withtheMRLs "willnotbehindered" bylegalprovisions.56Since theECmeasures
prohibited thedistribution ofbeeftreated withthese products forgrowth promoting purposes, itwas
clear thattheEuropean Communities hadnotaccepted these MRLs andhadnotbased itsmeasures
onthem.
4.65 The European Communities responded that international standards, guidelines or
recommendations werebased onacertain concept oflevelofsanitary protection. Butadifferent level
might require adifferent typeofmeasure. Thiswaswhatwasapplied bytheEuropean Communities
inthecaseofthehormones atissue: theEClevelofprotection aimed toattain noresidues inmeat
ofthese hormones, inother words, consumers should notbeexposed toanylevelofadded hormones
intheirfood. Toachieve thislevelofprotection, theonlyreasonably available andleastrestrictive
measure wastoapply aprohibition ontheuseofthese hormones forgrowth promotion. IntheEC
view, Canada hadnotshown thatdifferent measures were reasonably available totheEuropean
Communities. AllthatCanada argued wasthattheEuropean Communities should havefollowed the
Codex recommendations. However, theCodex recommendations were designed toachieve alevel
ofprotection which waslower thanthatapplied intheEuropean Communities.
4.66 Furthermore, theEuropean Communities considered thattheMRLs laiddown byCodex were
notmeasures butlevels ofprotection andtherewasnoobligation intheSPSAgreement toadopt Codex
recommended levels ofprotection. TheEuropean Communities added thateventhemeasures applied
byCanada initsterritory were notcapable ofrespecting thelevelrecommended byCodex because
Canada tested onlyaverysmall number ofanimals eachyear. Forzeranol, forexample, in1996 it
wasforeseen thatsamples ofonly650animals would betested. Fortrenbolone acetate samples of
only325animals, forMGA samples of275animals, andforthethree natural hormones samples of
only40animals. TheEuropean Communities argued thatnoprovision oftheSPSAgreement obliged
theEuropean Communities tolower itslevelofsanitary protection; onthecontrary, thepreamble
expressly stated thatMembers were notrequired tochange theirlevelofprotection.
4.67 TheEuropean Communities considered thatthere wasclearly scientific justification forits
measures. The1988JECFA Report, onwhose "scientific" advice Codex hadbased itsrecommended
MRLs, hadestablished anADIforzeranol of0-0.5µg/kg body weight, andfortrenbolone of0-
0.02µg/kg body weight. TheEuropean Communities wastherefore justified, inrespect ofzeranol
andtrenbolone, inaccepting thelower limit, i.e.anADIofzero.Codex hadmade norecommendation
forMGA. Forthe"natural" hormones, itwasknown thattheyhadadverse effects, which combined
withalackofknowledge oftheiraction, lackofdataontheeffect ofcombinations andthelackof
adefinition of"good veterinary practice", permitted theEuropean Communities toadopt adifferent
levelofprotection,i.e.ensureECconsumersthattherewerenoresiduesleftotherthantheonesnaturally
producedbytheanimalsthemselves.Infact,asthescientificopinionofDr.Liehrandtheotherscientists
advising theEuropean Communities inthiscasedemonstrated, these natural hormones andtheir
metabolites weremostlikely carcinogenic. TheEuropean Communities believed that,inviewofthe
potential hazards tohuman health presented bythesources ofriskreferred toinparagraphs 4.151 to
4.209, these hormones should onlybeadministered forthepurposes andunder theconditions defined
56Canada noted thatthe"General Principles oftheCodex Alimentarius," Paragraph 6.A.(i), Codex Alimentarius
Commission, Procedural Manual, 9thed.(Rome: Secretariat oftheJoint FAO/WHO Food Standards Programme, 1995),
p.45 stated:
"(i) FullAcceptance
Fullacceptance ofaCodex maximum limitforresidues ofpesticides orveterinary drugs infoods means thatthe
country concerned willensure, within itsterritorial jurisdiction, thatafood, whether home-produced orimported,
towhich theCodex maximum limitapplies, willcomply withthatlimit. Italsomeans thatthedistribution ofa
foodconforming withtheCodex maximum limitwillnotbehindered byanylegal oradministrative provisions
inthecountry concerned which relate tomatters covered bytheCodex maximum limit."WT/DS48/R/CAN
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intheECDirectives, which wereinaccordance withthe1993 "Codex Code ofPractice forControl
oftheUseofVeterinary Drugs" ("Codex Code ofPractice"). TheEuropean Communities further
argued thatthedistinction between agents which acted as"tumour initiators" and"tumour promoters"
wasclearly over-simplistic andwasnolonger applicable tothesehormones. Thisdistinction permited
some scientists tomake another prediction byextrapolating tumour incidence observed intestanimals
athighexposure levels topotential human exposure tolowlevels ofsuchhormones. However, as
shown byDr.Liehr, hormonal potency wasnotlinked toitscarcinogenic activity. Nevertheless,
itwasonthisdisputed extrapolation, based ontheNoHormonal Observed Level, thatJECFA had
based its1988 report andonwhich Codex hadbased itsrecommendations inJuly1995. The
European Communities argued thattheJECFA report hadbeenwritten in1988, thatitwasbased on
research andexperiments carried outabout tentofifteen years earlier, andthatitsrecommendations
wereadopted byCodex onlyin1995. There wasagapofabout 18to23years between theperformance
oftheexperiments andtheadoption oftheCodex recommendations.
4.68 TheEuropean Communities rejected Canada 'sstatement thattheCodex decision notto
recommend ADIs andMRLs forthethree natural hormones wasbecause residues ofthese hormones
werebelow anynumerical value thatwould ordinarily beassigned andargued thatJECFA could not
propose anADIbecause when itconsidered thematter, intheearly andmid1980s, thetechnology
formeasuring increases inlevels ofthenatural hormones wasnotsufficiently advanced tobeappropriate
forroutine use. Theprohibition ontheadministration ofnatural hormones toanimals forgrowth
promotion wasenforced intheEuropean Communities inseveral ways. ECmember States hadbeen
requested, inaccordance withtheconclusions oftheStanding Veterinary Committee, toinclude testing
onthenatural hormones intheirannual plans. Thus, theyneeded tocarry outtesting fornatural sex
hormones, inaccordance withDirective 86/469/EEC, onlivebovine animals atthefarmoratthe
slaughterhouse inorder todetermine whether thelevels ofthese hormones exceeded certain levels.
Forinstance, foroestradiol ortestosterone iflevels exceeding thelevels mentioned below werefound
intheblood plasma ofatleastonebovine animal, themeasures andinvestigations provided forin
Article 6,paragraphs 1,2and3ofDirective 85/358/EEC57should immediately beundertaken:
- 17-oestradiol: malebovine 18months 0.04ppb
female bovine nonpregnant 6months 0.04ppb
- 17-testosterone: malebovine 6months 10ppb
malebovine 6to18months 30ppb
female bovine nonpregnant 18months 0.5ppb
4.69 Inaddition tothetesting foroestradiol andtestosterone, ECmember States should control
theuseofgestagens inbovine animals forfattening, asthere wasapossibility ofmisusing gestagens
asgrowth promoters orforcamouflaging theapplication ofoestrogens. More than69,000 analysis
ofsamples forthedetection ofnatural hormones hadbeencarried outbyallECmember States during
1995. Moreover, incases ofsuspected use,analysis ofhormone levels inherds orgroups offattening
animals might beusedtoconfirm suspicion evenwhen natural hormones hadbeenused. Thiswas
because when thesehormones wereusedforgrowth promotion thiswasdoneusually byadministering
female hormones tomaleanimals andvice-versa. If,therefore, allormostofthesamples taken from
maleanimals showed highlevels offemale hormones there wasapresumption thatthese hormones
were notendogenous buthadbeenadministered. Taken inconjunction withother evidence which
hadgiven risetothesuspicion, suchanalytical results could confirm theadministration ofthehormones.
57TheEuropean Communities drew theattention inparticular toArticles 3,6,7and13ofDirective 96/23, which will
enter intoforce on1July1997.WT/DS48/R/CAN
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4.70 TheEuropean Communities further indicated thattheprohibition wasalsoenforced inpractice
byECmember States, whomaintained controls onthemanufacture anddistribution ofveterinary drugs
andmaintained surveillance ofagricultural practices (Article 4ofDirective 88/146/EEC andnow
Article 9ofDirective 96/22/EC). Illicit usewasdeterred bythesevere penalties imposed incases
ofproven misuse.
4.71 With regard toMGA, theEuropean Communities noted thatitwasauthorized forgrowth
promotion onlyintheUnited States andCanada, butapparently nowhere else. Codex hadnever
scientifically examined thishormone andhadnever recommended anystandard. Still,Canada inessence
argued thattheEuropean Communities should accept meattreated withMGA andcheck onlyforresidue
limits astheywere setbyCanada. Thisargument flewinthefaceoftheSPSAgreement, which
explicitly allowed theEuropean Communities toadopt alevelofprotection which itdeemed appropriate
(noresidue atall).TheEuropean Communities questioned whether Health Canada hadconducted any
newtestsonMGA orhadsimply relied onAmerican datafrom 1968.
4.72 AsregardedCanada,theEuropeanCommunitiesindicatedthatthereweretwoviolationsreported
in1995/96. Although forMGA therewasawithdrawal period of48hours priortoslaughter, itshould
notbetaken forgranted thatthisperiod would always berespected. There weremany reasons which
might leadtoitbeing disregarded, including labeldosage, absence ofcontrol byaveterinarian, the
sudden spread ofadisease orevenfluctuations inmarket prices were some reasons which might
precipitate slaughtering while active substances from implants orfeedstuffs were stillveryhigh.
Therefore, theEuropean Communities might choose toadopt ameasure which wasnomore trade
restrictive thanrequired toachieve itsappropriate level ofprotection, taking intoaccount technical
andeconomic feasibility, i.e.aprohibition ofuseofMGA foranimal growth promotion.
4.73 Canada noted thattheEuropean Communities hadargued that"[t]he MRLs laiddown byCodex
arelevels ofprotection andthere isnoobligation intheSPStoadopt Codex recommended levels of
protection". Canada submitted thattheECargument waspatently contrary totheobligation setout
inArticle 3.1: "...Members shall basetheirsanitary andphytosanitary measures oninternational
standards,guidelinesorrecommendations..."Codexadoptedstandardsonoestradiol-17,testosterone,
progesterone, zeranol andtrenbolone.58Thus, there wasaclearobligation under Article 3.1forthe
European Communities tobaseitssanitary measures onthese standards.
4.74 Canada explained thatanADIwasexpressed asarange, signifying thatanintake within the
range would beacceptable. Forzeranol, anintake of0µg/kg body weight would beacceptable, as
would anintake of0.5µg/kg body weight. Codex defined anMRL based onthetypeandamount
ofresidue considered tobewithout toxicological hazard forhuman health asexpressed bytheADI.59
AstheECMRLs forzeranol andtrenbolone were zero("noresidues"), theEuropean Communities
hadclearly notbased itsmeasures ontheCodex standards, pursuant toArticle 3.1.
4.75 Canada argued thattheECstated levelofprotection forthethree natural hormones, "...i.e.
ensure theECconsumers thatthere arenoresidues leftoverother thanthenaturally produced ones
bytheanimals themselves", reflected afundamental misunderstanding. Canada stated thatthiswas
notalevelofprotection, noranMRL. Thepurported riskposed byresidues ofthenatural hormones
would occur regardless ofwhether theresidues were produced endogenously oradministered
exogenously. Thus, theECmeasures didnotachieve ahigher levelofprotection withrespect tothe
natural hormones, asrequired byArticle 3.3.
58ALINORM 91/31, Appendix IVandALINORM 93/31, Appendix II,asadopted bythe21stSession ofCodex.
59Codex Alimentarius, Vol.3:Residues ofVeterinary Drugs inFoods," 2nd. ed.(Rome: FAO, 1996) p.76.WT/DS48/R/CAN
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(g) Article 3.3oftheSPSAgreement
4.76 TheEuropean Communities observed thatthemaintenance ofahigher level ofprotection
thanthatafforded byaCodex standard wasexplicitly allowed byArticle 3.3oftheSPSAgreement.
ThisArticle provided anexception totheobligation tobaseSPSmeasures oninternational standards:
"Members mayintroduce ormaintain sanitary orphytosanitary measures which result ina
higher levelofsanitary orphytosanitary protection thanwould beachieved bymeasures based
ontherelevant international standards, guidelines orrecommendations, ifthere isascientific
justification, orasaconsequence ofthelevelofsanitary orphytosanitary protection aMember
determines tobeappropriate inaccordance withtherelevant provisions ofparagraphs 1through
8ofArticle 5.Notwithstanding theabove, allmeasures which result inalevel ofsanitary
orphytosanitary protection different from thatwhich would beachieved bymeasures based
oninternational standards, guidelines orrecommendations shallnotbeinconsistent withany
other provision ofthisAgreement."
Afootnote tothisparagraph provided that:
"Forthepurposes ofparagraph 3ofArticle 3,there isascientific justification if,onthebasis
ofanexamination andevaluation ofavailable scientific information inconformity withthe
relevant provisions ofthisAgreement, aMember determines thattherelevant international
standards, guidelines orrecommendations arenotsufficient toachieve itsappropriate level
ofsanitary orphytosanitary protection."
4.77 Canada observed thatthefirstsentence ofArticle 3.3could bedivided intotwoparts. The
firstphrase setoutaprecondition forthedeparture from therelevant international standards: the
Member 'smeasures must result inahigher levelofsanitary orphytosanitary protection thanwould
beachieved bymeasures based ontheinternational (Codex) standards. Anyother departure wasnot
contemplated. Thesecond phrase presented twoalternative justifications forsuchadeparture: first,
scientific justification; second, asaconsequence ofthelevelofsanitary orphytosanitary protection
aMember determined tobeappropriate inaccordance withtherelevant provisions ofparagraphs 1
through 8ofArticle 5.Thefootnote toArticle 3.3provided thatthere wasscientific justification if
"...onthebasis ofanexamination andevaluation ofavailable scientific information inconformity
withtherelevant provisions ofthisAgreement, aMember determines thattherelevant international
standards, guidelines orrecommendations arenotsufficient toachieve itsappropriate levelofsanitary
orphytosanitary protection". Article 3.3alsorequired thatthemeasures notbeinconsistent withany
other provision oftheSPSAgreement.
4.78 Canada suggested thatthetwojustifications (i.e.,situations) weresimilar, andcomplementary,
butwere intended todealwithtwodifferent situations. Thefirstjustification wasintended todeal
withsituations where aninternational standard wasoutdated andneeded tobere-evaluated, andthat
standard didnotprovide thelevel ofprotection itwasthought tohave provided. Thus, "...an
examination andevaluation ofavailable scientific information inconformity withtherelevant provisions
ofthisAgreement ..."(interalia,Articles 5.1and5.2)revealed thattheinternational standard was
"...notsufficient toachieve [theMember 's]appropriate levelofsanitary orphytosanitary protection."
Thesecond justification contemplated asituation when aMember wished tomaintain ahigher level
ofprotection thanthatafforded bytheinternational standard, where thescientific analysis underlying
thestandard wasvalid. However, thesecond justification required thatthedifferent levelofprotection
be"....inaccordance withtherelevant provisions ofparagraphs 1through 8ofArticle 5."Thiswould
include theriskassessment requirements setoutinArticles 5.1and5.2,aswellastheconsistency
disciplines ofArticle 5.5.WT/DS48/R/CAN
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4.79 InCanada 'sview, theECmeasures failed tomeet these requirements forderogations from
theobligation inArticle 3.1infourways. First, withrespect tothethree natural hormones, theEC
measures failed toprovide ahigher levelofprotection thanwould beachieved bymeasures based on
theCodex standards. Since thelevels ofnatural hormones inbeefderived from untreated livestock
varied widely, depending uponthesex,ageandfertility cycle ofananimal, thelevels ofthesehormones
inbeefderived fromhormone-treated livestock werewellwithin thelevels ofnatural variation. Since
theEuropeanCommunitiesdidnotregulatetheexposureofconsumerstohigherlevelsofthesehormones
occurring inthemeatofuntreated animals, theECmeasures failed toachieve anypurported higher
levelofprotection. Canada claimed thatthenaturally occurring hormones, whether endogenous or
exogenous, were identical inchemical structure. Thefactthatthese substances were administered
exogenously hadnobearing onwhether ornottheywerecarcinogenic. Thus theECstated levelof
protection forthethree natural hormones, "...i.e.ensure ECconsumers thatthere arenoresidues
leftoverotherthanthenaturally produced onesbytheanimals themselves" wasnotalevelofprotection,
norevenaMRL. Thepurported riskposed byresidues ofthenatural hormones would occur regardless
ofwhether theresidues were produced endogenously, oradministered exogenously.
4.80 Canada noted, furthermore, thattheEuropean Communities didnotregulate theexposure of
consumers tofarhigher levels ofnatural hormones occurring inavariety offoods. Second, there
didnotappear tobeascientific justification forahigher level ofprotection. Anexamination and
evaluation ofavailable scientific information inconformity withtherelevant provisions oftheSPS
Agreement revealed thatthesixhormones inquestion didnotpresent anyharmful effects tothehealth
oftheconsumer when usedunder theappropriate conditions asgrowth promoters infarmanimals.
Third, since thelevelofprotection determined tobeappropriate bytheEuropean Communities was
notinaccordance withtherelevant provisions ofparagraphs 1through 8ofArticle 5,theECmeasures
could notbeavalidconsequence ofthatlevel. Fourth, theECmeasures wereinconsistent withArticle 5
oftheSPSAgreement. Canada submitted, therefore, thattheECmeasures werecontrary toArticle 3.
4.81 TheEuropean Communities argued thattheterm"appropriate levelofprotection" appeared
inArticle 3.TheSPSAgreement gavetherighttoMembers, when introducing ormaintaining their
measures ,tochoose between measures which resulted inalevel which washigher thanthatwhich
would result bymeasures based ontheinternational standards (Article 3.3), ifthere wasscientific
justification, oralevelofprotection which themember determined tobeappropriate. TheEuropean
Communities argued thatthetextofthefootnote toArticle 3.3confirmed thepower, which theSPS
Agreement lefttoMembers, tomake riskmanagement decisions thatreflected societal value choices
distinct from thestrict scientific process ofriskassessment. Asithadbeensaid:"thechoice of
appropriate levelofprotection appears tobetheunilateral prerogative ofeachWTO member State ..."60
4.82 TheEuropean Communities observed thatinbothoftheoptions provided inArticle 3.3,which
wereavailable toaMember when taking asanitary orphytosanitary measure ,theremusthaveexisted
"apotential riskforadverse effects". Inother words, itwasimplicit thatinorder toneedalevelof
protection there musthavebeensome hazard against which aMember needed toprotect. However,
thisonlyimplied theidentification ofahazard, notanassessment oftheprobability thatitwould cause
damage. TheSPSAgreement leftMembers freetodefine thelevelofprobability theywanted toassume:
thismight range fromzerotoinfinite; italsoleftthem freetodecide thetypeofmeasure theymight
choose toensure thatthelevelofprotection considered bythemtobeappropriate wasachieved. The
approach adopted bytheSPSAgreement wasinconformity withprevious GATT lawandpractice,
andwasasensible approach forthepurpose ofestablishing multilateral rulesanddisciplines toguide
60D.A. Wirth, "The RoleofScience intheUruguay Round andtheNAFTA Trade Disciplines", 27Cornell International
LawJournal, 817-859, at826(1994). TheEuropean Communities noted alsothattheUShadputitasfollows intheSAA:
"Intheend,thechoice oftheappropriate level ofprotection isasocietal value judgment ....TheSPSAgreement imposes
norequirement toestablish ascientific basis forthechosen levelofprotection because thechoice isnotascientific judgment ".WT/DS48/R/CAN
Page37
thedevelopment andprogressive harmonisation inorder tominimize thenegative effects ontradefrom
national sanitary andphytosanitary measures. Theapproach oftheSPSAgreement wasalsoin
conformity withdemocratic regulatory procedures, where frequently adichotomy wasoperated inthe
decision making process between: riskassessment andriskmanagement .Thefirstestablished strictly
thescientific basis forregulatory action. Thesecond (riskmanagement) wastheprocess bywhich
thecompetent authority ofaMember decided whataction totakeinthefaceontheassessment submitted
toitbythescientists. Such action wasbased onfactors suchaspublic health andenvironmental
protection, relevant legislation andlegalprecedent, application ofsocial, economic andpolitical values
andconsumer concerns. Theriskmanagement phase, therefore, inademocratic legislative system,
expressly recognized theimportance ofsocietal value choices.
4.83 TheEuropean Communities claimed thatthisseemed tobealsotheview ofCanada. Inits
Statement onImplementation fortheAgreement Establishing theWorld Trade Organization
(31December 1994, Canada Gazette, PartI,page4888), itwasstated:
"...Although itisnotnecessary formembers tobasetheirchosen levels ofprotection onrisk
assessment, theyshould work tominimize negative trade effects when choosing thelevel".
Theabove interpretation ofthedisciplines theSPSAgreement imposed onMembers wasapparently
supported alsobytheUnited States, since when theUSTR hadpresented theresults oftheUruguay
Round forapproval toCongress ithadstated :
"The SPSAgreement thusexplicitly affirms therightofeachgovernment tochoose itslevels
ofprotection, including a"zero risk" levelifitsochooses. Agovernment mayestablish its
levels ofprotection byanymeans available under itslaw,including byreferendum. Inthe
end,thechoice oftheappropriate level ofprotection isasocietal value judgement .The
Agreement imposes norequirement toestablish ascientific basis forthechosen level of
protection because thechoice isnotascientific judgement"61(emphasis added).
TheEuropean Communities wondered ifCanada agreed withtheabove statement fromtheUSStatement
ofAdministrative Action.62
61USStatement ofAdministrative Action, point 3(b).
62TheEuropean Communities argued thatthesame applied alsounder theNAFTA agreement, whose Article 712,para. 2
provides:
"Right toEstablish Level ofProtection .Notwithstanding anyother provision ofthisSection, each Party may, in
protecting human, animal orplant lifeorhealth, establish itsappropriate level ofprotection inaccordance with
Article 715".
TheEuropean Communities indicated thatArticle 715ofNAFTA laiddown anumber ofelements eachParty should take
intoaccount inconducting riskassessment, including, interalia,"relevant scientific evidence" (Art. 715(1)(b)). However,
paragraph 3ofArticle 715made itclear that,inestablishing itsappropriate level ofprotection, eachParty should onlyaim
atminimizing negative trade effects andshould avoid arbitrary orunjustifiable discrimination ordisguised restriction on
trade. Thechoice ofthelevelandthemeasure toachieve theprotection chosen, therefore, wasnotbased onscientific grounds.
Forexample, theformer Canadian Minister forinternational trade, thehonourable R.MacLaren hadstated that:
"The agreements [i.e.theSPSandNAFTA] make clearthatgovernments remain freetopursue legitimate regulatory
objectives, suchasconsumer safety andhealth protection. Every government mayestablish thelevels ofprotection
thatitconsiders appropriate. Inother words, nothing ineither theNorth American Freetrade Agreement orthe
WorldTradeOrganizationAgreementconstraintsagovernmentfromdeterminingthedegreeoftoleranceorprotection
itwishes." (Statement made during asaddress atCambridge University,United Kingdom, 17July1995).WT/DS48/R/CAN
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4.84 Inresponse tothearguments ofCanada thattheECmeasures didnotmeettherequirements
forderogation fromtheobligation tobasethemeasures onCodex 'srecommendations, theEuropean
Communities responded thatitwasnotpossible tolimitexposure ofitsconsumers toresidues from
thehormones occurring naturally inthemeatofuntreated animals. TheEuropean Communities did
notknow howonecould regulate thelevels ofresidues fromnaturally occurring hormones other than
banning allmeat andfoods from human consumption, butassumed thiswasnotwhat Canada was
suggesting. Thisargument ofCanada alsodisregarded thefactthathormones naturally occurring in
animals andother foods hadformed partofthehuman dietandhadentered themetabolism ofthehuman
body throughout thecourse ofhuman evolution. Thenaturally occurring hormones could notbe
comparedwithexogenouslyadministeredcarcinogenicsubstancesgiventoanimalsforgrowthpromotion.
AsDr.Liehr hadsaidinhiswritten opinion submitted tothePanel: "astheamount ofhormone or
metabolitenecessaryfortumourinductionisnotknown,theamountofexogenoushormoneormetabolite
necessary fortumour induction inaddition tounknown amounts ofendogenous hormone ormetabolite
havenotyetbeendetermined".
4.85 TheEuropean Communities further contended thatthisargument ofCanada alsoamounted
todictating thetypeofmeasures theEuropean Communities should putinplace inorder toachieve
thelevelofprotectionitalonemightdecide.ButtheSPSAgreementimposednorequirementtoestablish
ascientific basisforthechosen levelofprotection because thechoice wasnotascientific judgement.
Canada 'ssubmission, therefore, infactattacked notonlythelevelofprotection chosen bytheEuropean
Communities, butalsoitsmeasures, byinsisting thatresidues ofhormones above naturally present
levels didnotposeanyrisktohealth and,therefore, didnotwarrant theapplication ofanymeasures
tocontrol them other thanMRLs recommended byCodex Alimentarius. IfthePanel weretoaccept
thislineofargument, itwould inthefuture beopentoanycountry tooppose anyhealth measure which
wasbased ontheprecautionary principle. There were veryfewexamples ofhealth hazards where
allscientists agreed onthedegree ofrisk,andcountries might beallowed tomake judgments asto
what degree ofrisktheywere willing toaccept. ButtheSPSAgreement recognized thefactthat
scientific certainty wasrareandmany scientific determinations required judgments between differing
scientific views. TheSPSAgreement preserved theability ofgovernments tomake suchjudgments.
4.86 TheEuropean Communities stated thatCanada 'sargument amounted tooffering asolution
tosafeguard against thepotential risktohuman health from theuseofthese hormones forgrowth
promotion which theEuropean Communities hadconsidered carefully butrightly rejected, because
itdidnotmeetitsappropriate levelofprotection. TheEuropean Communities alsonoted thattheMGA
wasauthorized forgrowth promotion onlyinCanada andtheUnited States, butapparently nowhere
else. TheCodex Commission hadnever examined scientifically thishormone andhadnever
recommended anystandard. Intheview oftheEuropean Communities, Canada inessence argued
thattheEuropean Communities should accept meattreated withMGA andcheck onlyforresidue limits
astheyweresetbyCanada. TheEuropean Communities submitted thatthisargument would flyin
thefaceoftheSPSagreement, which explicitly allowed theEuropean Communities toadopt alevel
ofprotection which itdeemed appropriate (noresidue atall).Therefore, theEuropean Communities
could choose toadopt ameasure which wasnomore trade restrictive thanrequired toachieve its
appropriate levelofprotection, taking intoaccount technical andeconomic feasibility, i.e.aprohibition
ofuseofMGA foranimal growth promotion.
4.87 TheEuropean Communities alsoobserved thattheremaining threereasons invoked byCanada
initssubmissionwereunsubstantiated,becausetherewasagrowingpartof"available"scientificevidence
which argued thatthese hormones were dangerous tohuman andanimal health andtheEuropean
Communities wasbasing itsmeasures onthispartoftheavailable scientific evidence, astheSPS
Agreement clearly allowed ittodo.Initsview, there wereusually several ways ofdealing withany
given hazard, andtheSPSAgreement didnotrequire Members tochange thetypeofmeasure they
chose. Forexample, oneofthemany ways oftackling pathogenic organism infoodwasirradiation,
andsome Members allowed ittobeusedforcertain foods. Codex hadadopted standards forirradiationWT/DS48/R/CAN
Page39
offoods butthisdidnotmean thatevery Member wasnowobliged toallow irradiation ofallfoods.
Similarly, ifaMember hadchosen alevelofprotection against acontaminant onthebasisofanMRL,
thisdidnotmean thatitshould setitsMRL atthelevelrecommended byCodex. AlsoifaMember
hadchosen nottoallow anyresidue ofadangerous substance infood, thisdidnotmean thatitwas
obliged tobaseitsprotection ontheconcept ofanMRL recommended byCodex, ifoneexisted for
thatsubstance. Themaintenance ofahigher levelofprotection thanthatafforded byaCodex standard
wasexplicitly allowed byArticle 3.3.
4.88 TheEuropeanCommunitiesclaimedthatthetwosituationsreferredtoinArticle3.3as"scientific
justification" and"consequence ofthelevelofsanitary orphytosanitary protection aMember determines
tobeappropriate ..."clarified thecircumstances under which aMember mayderogate from the
provisions ofArticle 3.1.Inorder tounderstand properly thetwopossibilities envisaged, itwascrucial
tonotethedistinction between appropriate levelofsanitary protection, ontheonehand, andsanitary
orphytosanitary measures introduced ormaintained toachieve thelevelofprotection, ontheother.
Thisdistinction wasimportant, because paragraph 6ofthepreamble totheSPSAgreement made it
plainly clear thatharmonization ofsanitary measures withinternational standards, guidelines and
recommendations didnotrequire Members tochange theappropriate levelofprotection ofhuman,
animal orplant lifeorhealth which theyhadbeenapplying before theentry intoforce oftheSPS
Agreement.
4.89 The"scientific justification" wasapplicable tothefirsttypeofmeasures. Thisfollowed clearly
fromthetextofArticle 3.3,which hadacomma (,)afterjustification andthenstarted withtheword
"or". A"scientific justification" existed when theinternational standard, guideline orrecommendation
wasinadequate, faulty orobsolete fromthescientific pointofview. Thefootnote toparagraph 3clarified
thisverywell. Thefirstsituation appeared toconcentrate onthescientific dimension oftheinternational
standard, guideline orrecommendation. AMember might determine thatmeasures based onan
international standard could notachieve itslevelofprotection, because suchstandard wasbased, for
example, ononlypartoftheavailable scientific evidence, orwasbased onfaulty scientific evidence,
orwasoutofdatebecause ithadbeenovertaken bymore recent evidence, orwasbased ondifferent
climatic orenvironmental conditions thanthose prevailing intheMember concerned. Thescientific
justification referred onlytomeasures, nottothelevel ofprotection. Thiswasalsoinconformity
withtheother provisions oftheSPSAgreement, inparticular Article 2.2.
4.90 TheEuropean Communities further argued thataninternational standard, guideline or
recommendation implied acertain levelofsanitary protection. There might beseveral typesofmeasures
which could achieve thatlevelofprotection. Theobjective oftheSPSAgreement wastoharmonize
suchpossible measures. Buttheobjective oftheAgreement wasnottoharmonize thelevelofprotection
aMember considered appropriate initsterritory. Therefore, ifthelevelofprotection implied bythe
international standard andthelevel deemed appropriate byaMember were different, themeasures
toachieve thatMember 'slevelwerealsobound tobedifferent, especially when itslevelwashigher
thanthatimplied bytheinternational standard.
4.91 Thesecond situation clarified thataMember wasinanycaseentitled tointroduce ormaintain
measures which aimed atachieving thelevelofsanitary protection itdeemed appropriate initsterritory,
andthatsuchmeasures resulted inahigher levelofprotection thanthatwhich would result bymeasures
based ontherelevant international standard. Inthiscase, when determining itsappropriate levelof
protection, theMember hadtocomply withparagraphs 1to8ofArticle 5.Paragraphs 1,2,3,6,
7and8dealtwiththeassessment oftheriskandthetypeofmeasures aMember maytake. Paragraphs 4
and5dealtwiththeissueofdetermining thelevelofprotection. Butparagraphs 4and5didnotindicate
howthelevelofsanitary protection initselfwastobedetermined. TheEuropean Communities recalled
itsargument thatthelevelofprotection wasnotascientific judgment andaMember wasfreetoapply
thelevel ofsanitary protection itdeemed appropriate initsterritory. Paragraph 4(which wasnot
mandatory) andparagraph 5(which wasonlyanobjective tobeimplemented through guidelines yetWT/DS48/R/CAN
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tobedeveloped) attempted toplace onlycertain constraints ontheliberty ofMembers toimplement
thelevelofprotection theyhaddetermined. Inother words, theyshould (notshall)takeintoaccount
theobjective ofminimizing trade effects andshallavoid arbitrary orunjustifiable distinctions inthe
levels, ifsuchdistinctions result indiscrimination ordisguised restriction oninternational trade.
Therefore, noneoftheparagraphs ofArticle 5dealtwithsetting thelevelofprotection perse.
4.92 TheEuropean Communities observed thatin1989thedetailed provisions oftheSPSAgreement
werenotinplace andtheGATT 1947caselaw,inparticular theThaiCigarettes Panel report of1990,
hadclearly acknowledged therightofMembers totakesanitary orphytosanitary measures provided
theprovisions ofthe"chapeau" ofArticle XXwererespected. On1January 1995, theWTO Agreement
anditsannexes hadentered intoforce. Stillatthattimethere werenoCodex standards, which were
adopted onlyinJuly1995. TheEClevelofprotection forthese hormones hadbeenthesame both
before andaftertheentry intoforce oftheSPSAgreement. The6thparagraph ofthepreamble of
theSPSAgreement alsoprovided thatinharmonizing theirmeasures tointernational standards Members
werenotrequired tochange theirappropriate levelofprotection ofhuman, animal orplant lifeor
health .Therefore, theSPSAgreement could notforce theEuropean Communities tochange thelevel
ofprotection ithadbeenapplying legally since 1989. Ifthemeasures ofaMember didnotfollow
international standards, there should benonegative inference thattheyviolated theprovisions ofthe
SPSAgreement orGATT. Theburden ofproof wasonthecomplaining party toestablish thealleged
violations. Since Canada argued thattheEuropean Communities hadnoscientific justification, itneeded
toprove onthebasis ofthescientific evidence oftoday howtheEuropean Communities could achieve
itshigher levelofprotection, ifithadbased itsmeasures onthestandards ofCodex. TheEuropean
Communities concluded thatwhen itdecided tomaintain itslevelanditsmeasures forthesehormones,
therewasnointernational standard tocompare themwith. Inaddition, on1January 1995, theEuropean
Communities clearly hadascientific justification foritsmeasures. In1988, theEuropean Communites
hadexamined theavailable scientific information andfound itdeficient andinadequate toguarantee
itslevelofsanitary protection. Inaddition, atthetimeofentry intoforce oftheSPSAgreement, the
European Communities haddecided tomaintain itsmeasures because itwasclear thattheevidence
onwhich the1988 JECFA report wasbased outofdate. Atthattime, theEuropean Communities
haddecided thatthedraftJECFA MRLs werenotsufficient toachieve itsappropriate levelofsanitary
protection.
4.93 TheEuropean Communities claimed thatthelegal question ofjustification arose onlyafter
July1995,whentheCodexCommissionadoptedtherecommendedMRLsforthetwosynthetichormones
anddecided nottoadopt MRLs forthethreenatural hormones. Thedecision oftheCodex Commission
ofJuly1995made nodifference fromthescientific point ofview, because itwasbased onevaluation
ofscientific information dating from 1987 orearlier. Thisscientific information hadbeenreviewed
andevaluated several times bytherelevant bodies oftheEuropean Communities asregarded these
hormones forgrowth promotion; andtheEuropean Communities hadconstantly rejected itonscientific
aswellasother grounds. Suchother factors included conditions ofuseofthese hormones forgrowth
promotion, potential formisuse, effectiveness ofdetection andcontrol, synergistic effects, long-term
exposure, etc.Itshould alsobeborne inmind thatJECFA andCodex hadnever evaluated these
hormoneswhenusedfortherapeuticorzootechnicalpurposes.63TheEuropeanCommunitieshaddecided
again tomaintain itsmeasures inforce because ithadbothascientific justification andbecause its
appropriate levelofsanitary protection forthese hormones wasthesame before andafterthatdate,
i.e.higher thanthatwhich could beachieved bymeasures based onCodex standards. Thescientific
information which hadbeenemerging since themid1980'shadreinforced thescientific basis upon
which theEuropean Communities hadalready decided toprohibit theuseofthesehormones forgrowth
63TheEuropean Communities argued thatitfollowed thattheevaluation theEuropean Communities hadmade in1993/94
ofoestradiol-17 fortherapeutic orzootechnical purposes wastotally irrelevant tothisdispute, because itwasnotmade
for,nordiditaffect, theriskassessment theEuropean Communities hadmade forthefiveofthese hormones when used
asgrowth promoters.WT/DS48/R/CAN
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promotion. Thenewly emerging evidence supported clearly theviewthatthese hormones (oratleast
some ofthem) were genotoxic andcarcinogenic and,therefore, notolerance levels could befixed.
AsDr.Lucier andthescientists advising theEuropean Communities hadsaid,theJECFA Report of
1988 wasclearly outofdateatthattime. Thisreport wascertainly inneedofreview inJuly1995,
inApril 1996 andevenmore today.
4.94 TheEuropean Communities explained thatithadstarted theprocess ofreviewing thescope
ofapplication ofDirective 88/146 since 1993, inorder toexpand itsapplication tonewsubstances
(likebeta-agonists) andtoreinforce itsprovisions oncontrol, testing and,inparticular, toincrease
thefinesandpenalties forviolators. Thisreinforcement inthelegislation wasrequested bytheEuropean
Parliament, inthelightofthereports ithadprepared onthese substances. Whilst thisproposal was
beingdiscussed,theSPSAgreementhadenteredintoforceand,consequently,theEuropeanCommunities
hadreviewed itsmeasures andhaddecided tomaintain theprohibition ontheuseofthese hormones
forgrowthpromotion.WhiletheproposalwhichhadledtotheadoptionofDirective96/22waspending,
theEuropeanCommunitieshadalsoorganizedthe1995ScientificConferenceinDecember1995,mindful
ofitsinternational obligations under theSPSAgreement. Thisconference wasinitself notarisk
assessment, inthesense ofArticles 5.1and5.2,because theconcept ofriskassessment, asexplained,
wasmuch wider andencompassed theother elements mentioned therein. Thiswasmade clearfrom
thediscussion withthescientists. Butonthebasisofsome ofitsscientific conclusions, together with
theother pieces ofscientific information which werealready available onthese hormones, andafter
consulting withtheappropriate legislative bodies, theEuropean Communities haddecided tomaintain
theprohibition ontheuseofthese hormones forgrowth promotion (i.e.ithaddecided tomaintain
themeasures )andalsotoexpand theircoverage toother substances andtoincrease controls andthe
levels offines. Thiswascontained inDirective 96/22 ofApril 1996, which would enter intoforce
on1July1997.
4.95 IntheviewoftheEuropean Communities, Canada hadtoshow onthebasisoftoday'sscientific
evidence thatthemeasures theEuropean Communities maintained inplace afterJuly1995 violated
theprovisions oftheSPSAgreement. However, instead ofusing thescientific evidence oftoday,Canada
hadbeenusing thescientific evidence ofJECFA 1988(andthemuch earlier evidence oftheLamming
Committee reports). Thisscientific evidence wasclearly outofdate,asallthescientists advising the
European Communities (andsome ofthescientists advising thePanel) hadpointed outintheirreports.
AsDr.Ritter hadsaidinoneofhisreplies, "thecurrent weight ofscientific evidence would, however,
appear tocontinue tosupport theview...thatatpresent there isnoevidence forpossible health risks
totheconsumer duetotheuseofthenatural sexhormones forgrowth promotion ...".Butthiswas
thepersonal viewofDr.Ritter about thecurrent weight ofscientific evidence. Since 1989, thescientific
andlegislative bodies oftheEuropean Communities viewed theweight ofscientific evidence differently.
TheSPSAgreement didnotrequire unanimity indeciding whatwastherelevant scientific evidence
before aMember wasallowed totakesanitary measures ;people didnothavetostartdying before
apreventive measure could betaken.
4.96 TheEuropean Communities considered therefore thatithaddoneallitcould toconform with
itsinternational obligations. Ithadreviewed themeasures andhaddecided tomaintain them, in
accordance withtheprovisions oftheSPSAgreement, because ithadascientific justification. The
othergrounds formaintaining themincluded conditions ofuseofthesehormones forgrowth promotion,
potential formisuse, effectiveness ofdetection andcontrol, synergistic effects, long-term exposure,
etc.Ithadalsoreviewed, evenifitdidnothaveto,itslevelofprotection inthiscase,andhaddecided
tomaintain itasitwasbefore theentry intoforce oftheSPSAgreement withregard totheuseof
these hormones forgrowth promotion. Itcould notachieve itslevelofprotection byother measures
based onthestandards adopted byCodex inJuly1995, which would havebeensignificantly less
restrictive ontrade. Theextremely small number ofcontrols performed byCanada andthenumber
ofviolations stilldiscovered within thisextremely lownumber ofcontrols demonstrated thattherewas
noothermeasure which could achieve itslevelofprotection andwhich wastechnically andeconomicallyWT/DS48/R/CAN
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feasible and,inaddition, significantly lessrestrictive ontrade. AtleastCanada hadnotbeenableto
demonstrate theexistence ofsuchanalternative measure. TheEuropean Communities hadalsoshown
thatanytypeoflabelling inthiscasedidnotwork.
(h) Article 5oftheSPSAgreement
4.97 Canada noted thatanunderstanding ofhowscientists evaluate riskisessential toanoverall
understanding ofthesafety ofveterinary drugs usedinanimal husbandry. Riskanalysis hadbeendefined
bytheJointFAO/WHO Expert Consultation asmeaning "...aprocess consisting ofthreecomponents:
riskassessment, riskmanagement, andriskcommunication".64Attheendoftheprocess, asanitary
measure might beputinplacetocontrol anidentified health risk(s). Thetypeofmeasure chosen related
totheseverity oftheriskandtheleasttraderestrictive riskmanagement option(s), asidentified during
theriskanalysis process. Initsmost recent draft, Codex haddefined riskas"...afunction ofthe
probability ofanadverse health effect andtheseverity ofthateffect, consequential toahazard(s) in
food".65Codex acknowledged thathazards werepresent infoodasaresult ofchemical contaminants
(e.g.,pesticides andveterinary drugresidues), microbiological contaminants, ornaturally occurring
substances (e.g.,toxins) found infood. These hazards presented arisktohuman health. Risk
assessment, which wasonecomponent intheriskanalysis process, permitted anobjective evaluation
ofthese hazards.
4.98 Canada noted thattheSPSAgreement required thatachosen sanitary measure bebased on
anappropriate riskassessment. Riskassessment wasaprocess thatrecognized theinherent uncertainties
inconducting ascientific evaluation oftheeffects certain hazards posed tohuman health. Thus, the
riskassessment process wasdesigned tobeconservative andrequired extensive testing andanalysis
when evaluating potential human health hazards. Riskassessment wasaspecific component ofthe
riskanalysis process which, conducted byscientists, included welldefined procedures thathadbeen
described byCodex andJECFA. Inthemostrecent report oftheJointFAO/WHO Expert Consultation
ontheapplication ofriskanalysis tofoodstandard issues, theriskassessment process wasdefined
ashaving fourcomponents:
(i) hazard identification
(ii) hazard characterization
(iii) exposure assessment
(iv) riskcharacterization.66
4.99 Canada noted thatriskassessment systematically organized scientific andtechnical information
toanswer specific questions about health risksandrequired explicit recognition thatthere might be
someuncertainties, owing either tolimits inthedata,ortoalternative interpretations ofthedata. Canada
submitted thefollowing explanation ofthefourcomponents oftheriskassessment process according
totheCodex report.
64"Application ofRiskAnalysis toFood Standards Issues: Report oftheJointFAO/WHO Expert Consultation, Geneva,
Switzerland, 13-17 March 1995" (Geneva: WHO, 1995) p.6[hereinafter: "Application ofRiskAnalysis toFood Standards
Issues: Report oftheFAO/WHO Expert Consultation"]. Canada submitted thatthiswasthemost recent comprehensive
international report onriskanalysis, butstressed thatCodex definitions forriskanalysis continued toevolve. InJune1996,
Codex hadissued revised definitions forinterim use. These definitions were found in:Codex Alimentarius Commission,
"Terms andDefinitions Used inRiskAnalysis," JointFAO/WHO Food Standards Programme, June1996, p.2[hereinafter
"Terms andDefinitions used inRiskAnalysis"].
65Ibid.,"Terms andDefinitions used inRiskAnalysis".
66"Application ofRiskAnalysis toFood Standards Issues: Report oftheFAO/WHO Expert Consultation", supra note64.WT/DS48/R/CAN
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4.100 Hazard Identification wastheidentification ofbiological, chemical andphysical agents capable
ofcausing adverse health effects, andwhich might bepresent inaparticular foodorgroup offoods.67
Canada indicated thatindealing withveterinary drugresidues, thegoalwastoidentify potential adverse
health effects inhumans associated withexposure toaveterinary drug. Thequalitative likelihood of
sucheffects occurring inexposed human populations, andthecertainty oruncertainty associated with
sucheffects, wereevaluated using available data. These datamight bederived fromanumber ofsources,
suchasepidemiological studies oranimal toxicological studies.68Iftherewasanyevidence ofahazard,
thenthehazard characterization process oftheriskassessment wasundertaken.
4.101 Hazard Characterization wasthequalitative and/or quantitative evaluation ofthenature of
theadversehealtheffectsassociatedwithbiological,chemicalandphysicalagentswhichmightbepresent
infood. Forchemical agents, suchasveterinary drugs, adose-response assessment wasperformed.69
Canada added thatinallcases, thechemicals being considered forhazard characterization werepresent
atverylowlevels infoods, thatis,parts permillion ("ppm") orless. Therefore, toobtain adequate
sensitivity inhumans, animal toxicological studies wereoftenconducted atveryhighlevels, sometimes
exceeding several thousand ppm's.70Asafelevel orAcceptable Daily Intake ("ADI") wasderived
from theexperimental NoObservable Effect Level ("NOEL") ortheNoObserved Adverse Effect
Level ("NOAEL") byapplying anappropriate safety factor. When datafromlong-term animal toxicity
studies wereavailable, asafety factor of100wasgenerally applied. Larger safety factors, upto1000,
might beusedincertain cases. Thismeant thattherewasnosignificant riskifthechemical wasingested
atorbelow theADIandthelikelihood ofadverse health effects wasnotionally zero.
4.102 Canada submitted thattraditionally, toxicologists haveaccepted theexistence ofthresholds
foradverse effects withtheexception ofcarcinogenicity. Thiswasbecause genotoxic carcinogenic
compounds hadtheability toproduce mutations ingenetic material (DNA) leading totumour formation.
Inrecent years, however, ithadbeenpossible todiscriminate between genotoxic carcinogens andnon-
genotoxic carcinogens. Thelatter werethemselves notcapable ofproducing mutations, although there
might beaneffect oncellsthatwerealready intheprocess ofmutating. Hazard characterization now
distinguished between genotoxic andnon-genotoxic carcinogens.71Inprinciple, non-genotoxic
carcinogens might beregulated using ADIs derived fromanexperimental NOEL orNOAEL, andby
applying appropriate safety factors (the"threshold approach").
4.103 Forgenotoxic carcinogens, the“NOEL-safety factor ”approach wasgenerally notconsidered
asuitable method forsetting ADIs. Twoapproaches were available: (i)tobanthechemical from
commercial use,or(ii)toestablish alevelofriskthatwassufficiently small tobedeemed negligible
orinsignificant. Forgenotoxic carcinogens, inestablishing anegligible levelofrisk,aquantitative
riskassessment process wasused.72Thisapproach hadbeenusedtoestablish aMRL forcarbadox,
67"Terms andDefinitions used inRiskAnalysis" ,supra note57.
68"Application ofRiskAnalysis toFood Standards Issues: Report oftheFAO/WHO Expert Consultation", supra note64.
69Dose response assessment wasdefined as,"...the determination oftherelationship between themagnitude ofexposure
(dose) toachemical, physical orbiological agent andtheseverity and/or frequency ofassociated adverse health effects":
"Terms andDefinitions used inRiskAnalysis", supra ,note57.
70"Application ofRiskAnalysis toFood Standards Issues: Report oftheFAO/WHO Expert Consultation", supra ,note64.
71Canada explained thatnon-genotoxic carcinogens were referred toas"promoters"; thatis,theydidnotcause cancer,
butrather theycould actaspromoters incellsthathadalready beendamaged. Non-genotoxic carcinogens were notcapable
ofproducing mutations. Incontrast, genotoxic carcinogens were "initiators", andcould cause mutations ofDNA resulting
intumours inhumans oranimals.
72"Application ofRiskAnalysis toFood Standards Issues: Report oftheFAO/WHO Expert Consultation", supra, note64.WT/DS48/R/CAN
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which hadametabolite thatwasaknown genotoxic carcinogen. Carbadox waspermitted forusein
theEuropean Communities asafeedadditive. Thefirstapproach, tobanthecompound, hadbeen
adopted byseveral countries, including theEuropean Communities, fornitrofurans, which werealso
known genotoxic carcinogens.
4.104 Exposure Assessment wasthequalitative orquantitative evaluation ofthelikely intake of
biological, chemical orphysical agents viafood, aswellasexposures fromother sources ifrelevant.73
Canada explained thatthiswasusually donebyexamining thedietary intake offoods anddetermining
ifthetheoretical dietary intake wasbelow therecommended ADIs.
4.105 RiskCharacterization wasthequalitative and/or quantitative estimation oftheprobability of
occurrence, andseverity, ofknown orpotential adverse health effects inagiven population based on
hazard identification, hazard characterization andexposure assessment.74
4.106 CanadaindicatedthatriskmanagementhadbeendefinedbyCodexas"...theprocessofweighing
policy alternatives inthelight oftheresults ofriskassessment and,ifrequired, selecting and
implementing appropriate control options, including regulatory measures".75Itwastheviewofthe
JointFAO/WHO Expert Consultation that"...riskassessment ofchemical hazards infoods usually
results intheselection ofriskmanagement options toensure thatfoodborne riskstoconsumers are
notappreciable ('notionally zero')".76Thesetting ofMRLs wasariskmanagement option thatwas
commonly usedincontrolling therisksarising from chemical contaminants (e.g.,veterinary drugs)
infoods. Coupled withmonitoring andtesting programs, itwasanexample ofacomprehensive sanitary
control measure thatcould beusedtomanage riskeffectively.
4.107 Canada noted thatriskcommunication wasdefined byCodex as,"[t]he interactive exchange
ofinformation andopinions concerning riskamong riskassessors, riskmanagers, consumers andother
interested parties".77Canada submitted thatriskcommunication must takeplace atallstages ofthe
riskanalysis process toensure open, balanced andmeaningful discourse between science experts, policy
makers, farmers, industry, consumers andallother interested parties.
4.108 TheEuropean Communities argued thatthescientific evidence onwhich hormone growth
promoters wereapproved, mostofitgathered bydrugcompanies andstillsecret, wasobtained using
primitive techniques which would notbeacceptable today. Forexample, theCodex decision of1995
onthegrowth promoting hormones hadbeentaken onthebasisofscientific papers dating backtothe
1940s and,inonecase,to1939. TheEuropean Communities argued thatthesystem described under
"Application ofRiskAnalysis toFood Standards issues" hadnotbeenapproved byCodex. Thewhole
subject ofriskanalysis hadbeenunder discussion invarious bodies ofCodex forseveral years but,
precisely because therewasnointernational consensus onthesubject, nothing hadbeenagreed. Codex
hadnotevenbeenabletoagree definitions ofthevarious terms used, letalone procedures fortheir
application. AttheCodex Committee onGeneral Principles (Paris, November 1996) ithadbeenagreed
toforward adraftlistofdefinitions totheCodex Alimentarius Commission meeting in1997 forit
toagree totheiruseonaninterim basis, pending further clarification. TheEuropean Communities
73"Terms andDefinitions used inRiskAnalysis," supra ,note64.
74Ibid.
75Codex Alimentarius Commission, "Risk Analysis: Definitions, Procedures andPrinciples, Joint FAO/WHO Food
Standards Programme, Codex Committee onGeneral Principles -Twelfth Session", Paris, France, 25-28 November 1996
p.18 (hereinafter "Risk Analysis: Definitions, Procedures andPrinciples").
76"Application ofRiskAnalysis toFood Standards Issues: Report oftheFAO/WHO Expert Consultation", supra ,note64.
77"Risk Analysis: Definitions, Procedures andPrinciples".WT/DS48/R/CAN
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submitted thatameasure might beapplied toprotect against asuspected hazard, notonlyagainst "an
identified health risk" asclaimed byCanada. Thetypeofmeasure neednotrelate totheseverity
oftherisk,norneeditbetheleasttrade restrictive option. Thecriteria forthechoice ofmeasures
weresetoutintheSPSAgreement, which didnotmention the"severity" oftherisk. Thesame type
ofmeasure might beusedforrisksofdifferent severity: forexample vaccination wasameasure widely
usedagainst risksofverydifferent severity.
4.109 Thequestion oftrade-restrictiveness wasaddressed inArticle 5.6,which didnotrequire the
"least" trade-restrictive option; itrequired Members toensure thattheirmeasures were "notmore
trade-restrictive thanrequired toachieve theirappropriate levelofsanitary orphytosanitary protection,
taking intoaccount technical andeconomic feasibility". Inthecaseofgrowth hormones, itmight appear
tobeleasttrade-restrictive toallow trade inallmeatfromtreated animals aslongasnoresidues were
present init.However, oncethetechnical andeconomic problems ofensuring theabsence ofresidues
(control oversupply anduse,testing ofmeat, etc.)weretaken intoaccount, thisoption would infact
bemore trade-restrictive thanthemeasures applied bytheEuropean Communities.
4.110 Noting thattherewasaperfectly satisfactory definition ofriskassessment already intheSPS
Agreement, Annex A(4), which expressed riskas"thepotential foradverse effects", theEuropean
Communities noted thatdisease anddeath werenottheonlyadverse health effects which might result
from thepresence ofaresidue infood-there might alsobeunwanted physiological consequences.
Forexample, theEuropean Court ofJustice, having referred explicitly totheconstitution oftheWHO,
which defined health as"astateofcomplete physical, mental andsocial well-being thatdoesnotconsist
onlyintheabsence ofillness orinfirmity", hadconcluded thatabroad interpretation should begiven
accordingly totheconcept ofhealth contained inaprovision ofEClaw.78
4.111 TheEuropeanCommunitiesrecalledthattherewasnointernationallyagreedobjective,scientific
process which could deliver amathematically precise riskassessment. Thestatement inCanada 's
submission that"there maybesomeuncertainties" wasanunderstatement, particularly intheassessment
ofbiological hazards tohuman health where direct testing onhumans wasnotpossible andindividuals
varied greatly intheir responses tosubstances. Hazard identification consisted ofexactly that-
identification ofahazard. Theprocesses ofevaluating thelikelihood (exposure assessment) andseverity
ofeffects (riskcharacterization) were laterstages inriskassessment. Thereason Canada triedto
introduce theselaterstepsintothehazard identification wasthataMember needed onlyidentify ahazard
inorder tosetalevelofprotection. TheSPSAgreement didnotrequire afurther assessment ofthe
hazard inquantitative terms, asCanada pretended, inorder foraMember todecide thatitdidnotwant
anyofthehazard present initsfood.
4.112 TheEuropean Communities further argued thatadose-response assessment could notbemade
forallchemicals inallcircumstances. Thiswasthecase, forinstance forgenotoxic substances. It
wasnotcorrect toassume thatthechemicals under consideration were always present onlyat"very
lowlevels infoods". Insome situations, forexample implant sitesofhormones, theymight bepresent
atquite highlevels. Finally, theconcept thattoxicity testing inanimals wasavalid testoftoxicity
inhumans wasnota"principle": itwasanassumption based onextrapolations which inthepasthad
notalways beenjustified (e.g.thalidomide, DES, etc.).
4.113 TheEuropeanCommunitiesnotedthatonthequestionofgenotoxiccarcinogensCanadasubmitted
quotes from page17oftheReport oftheJoint FAO/WHO Expert Consultation ontheApplication
ofRiskAnalysistoFoodStandardsIssues,insupportoftheirstatementthataquantitativeriskassessment
"isused" toestablish a"negligible orinsignificant" risk. However, page18ofthatReport wenton
tostatethat,withrespect tothisapproach: "Itisacknowledged bymany regulatory agencies thatactual
78Case C-84/94, United Kingdom v.Council, judgment of12November 1996 (1996 ECR I-5800, para. 15).WT/DS48/R/CAN
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orprobable human risks arenotbeing predicted.", and"....thechoice ofarisklevel isultimately
ariskmanagement decision foreachcountry todecide."
4.114 TheEuropean Communities added thatthesetting ofMRLs wasnota"measure" initself.
AnMRL wasalevelofprotection -themonitoring, testing andcontrol programmes toenforce the
MRL were the"measures" inthesense oftheSPSAgreement. TheEuropean Communities added
thatitwasinterestingtoreadthatCanadawasnowinfavourof"open,balancedandmeaningfuldiscourse
between scientific experts, policy makers, farmers, industry, consumers andallotherinterested parties".
Thiswasinsharp contrast tothecriticism which itmade oftheEC1995Scientific Conference, where
itconsidered thattheparticipation of"non-scientific representatives ofvarious interest groups" led
toa"biased process withquestionable conclusions".
4.115 TheEuropean Communities alsoargued thatthe1988JECFA Report hadfound thattherewas
apotential risktohuman health, because ifthere werenosuchpotential risk,theJECFA would not
haverecommended anyADIandMRL forthetwosynthetic hormones. Forthethreenatural hormones,
JECFA hadnotrecommended anADIandMRL because ofproblems indetecting thelevelofresidues
inthemeatonaroutine basis.
4.116 TheEuropean Communities noted inthisregard thatscientists hadsaidthat"theADI-model
isnotariskmodel anddoesnotpredict theriskoftheoccurrence ofadverse effects, when ADI-values
areexceeded".79Thesame wasbasically truefortheMRL-model "which specifies thequantity of
aparticular residue inmeatthat,evenindietary extremes, would notexceed theADIfortheparticular
substance concerned".80TheEuropean Communities concluded thattheMRL wasbased onthenotion
thatthere wasarisk,butiftheproposed threshold wasobserved theprobability oftheadverse effect
arisingfromtheuseofhormoneswouldnotmaterialize.Inthiscase,theJECFArecommendedstandards
would achieve "alevelofprotection" against therisk. ButtheSPSAgreement allowed Members to
determine another level, i.e.theleveltheydeemed appropriate. Thislevelmight behigher orlower.
4.117 Canada recalled thatlevelofprotection (orlevelofrisk)described theprobability ofanadverse
health effect arising from acertain source. Theappropriate levelofprotection (oracceptable level
ofrisk)wastheleveldeemed appropriate (oracceptable) byaMember. ItwasclearthattheEuropean
Communities werenotunfamiliar withthenotion ofexpressing alevelofprotection, anditsappropriate
levelofprotection, intheseterms (paragraph 4.124). However, theEuropean Communities described
itsappropriate levelofsanitary protection inthiscasetobe"...noresidues ofthese hormones inmeat
destined forhuman consumption"81andhadclarified thisstatement, claiming thatitwasequivalent
tosetting maximum residue limits ("MRLs") ofzeroforthesixhormones atissue. Canada rejected
theECargument thatMRLs werelevels ofprotection. MRLs didnotdescribe thelevelofriskthat
aMember would accept, but,weresanitary measures usedtoachieve anappropriate levelofprotection
from aparticular sanitary risk.
4.118 Canada observed thattheEuropean Communities hadimplicitly admitted thedifference between
aMRL andanappropriate levelofprotection: "...amember maydecide instead ofimposing astricter
MRL toprohibit altogether theuseofthesubstance inthefirstplace, ifthisistheonly'reasonably
available alternative taking intoaccount technical andeconomic feasibility thatachieves itsappropriate
79H.A. Kuiper, "Risk Assessment Strategies forXenobiotics", 1995 ECScientific Conference Proceedings, p.375.
80"Report andConclusions", 1995 ECScientific Conference Proceedings, p.4.
81Canada noted thattheEuropean Communities hadalsostated thatitslevelofprotection withrespect tothethree natural
hormones wasto"...ensure theECconsumers thatthere arenoresidues leftoverother thanthenaturally produced ones
bytheanimals themselves".WT/DS48/R/CAN
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levelofsanitaryorphytosanitaryprotectionandissignificantlylessrestrictiveontrade'".82Aprohibition
ontheuseofasubstance wasasanitary measure usedtoachieve anappropriate levelofprotection.
Incomparing a"stricter MRL" with another sanitary measure, itwasclear thattheEuropean
Communities acknowledged thatanMRL wasasanitary measure. Canada submitted thattheEuropean
Communities hadfailed toarticulate ameaningful appropriate levelofprotection withrespect tothe
purported riskresulting from thepresence ofhormone residues, including theirmetabolites, inthe
meatfrom animals treated withthesixhormones atissue.
4.119 Canada noted thattheECdiscussion ofappropriate levelofprotection wasinaccurate inseveral
respects. First, asatechnical matter, theECterminology wasnotaccurate. Probability ranged from
zero(nooccurrences) toone(occurrence). Itwasoften expressed asafraction orapercentage. It
could not,however, begreater thanone,letalone infinite. Second, while aMember might define
thelevelofprobability itwanted toassume (acceptable levelofrisk), itwasclearthatinfashioning
ameasure tomeetthatlevelofprotection, itwasnotsufficient merely toidentify ahazard. There
mustbeanassessment oftheprobability thatthehazard would cause adverse health effects. This"risk
characterization" wasanessential partofriskassessment83,andwasintegral totheriskassessment
obligation setoutinArticle 5.1.Without thisinformation, themeasure taken toachieve thelevelof
protection might wellbemore trade restrictive thanrequired.84Finally, while itwasuptoaMember
todecide onthetypeofmeasure usedtoensure thattheappropriate levelofprotection wasachieved,
Article 5.6andArticle 2.2putlimits onthemeasure chosen.
4.120 TheEuropean Communities responded thatitslevelofprotection inthecaseofthesehormones
when usedforgrowth promotion inother countries wasnoresidues inmeat destined forhuman
consumption. Many different kinds ofbiological, chemical orphysical hazards might occur infoods,
andgovernments hadtodecide towhatdegree theywould attempt toprotect theirpopulations from
these hazards. These decisions weretaken, aswereanypolitical decisions, inthelightofanumber
offactors including thepotential danger tohealth andthecostandfeasibility ofachieving effective
protection. There would obviously alsobedifferences between governments intheirapproach tosetting
alevelofprotection, asafunction oftheireconomic priorities andcultural habits. Forexample, a
developed country might consider itdesirable tosetahighlevelofprotection against contamination
offoods bywaste material fromthechemical industry, whereas adeveloping country might consider
itahigher priority toencourage theestablishment ofachemical industry rather than, forthepresent,
toworry about chemical residues infood. Thiswasparticularly thecaseforcountries where food
supply wasmore ofaproblem thanfoodquality .Similarly, cultural habits suchastheeating ofcertain
foods inarawstatemight cause agovernment tosetahigher levelofprotection against certain pathogens
thanwould bethecaseforagovernment whose population tended tocookthesame foodthoroughly
before eating it.TheEuropean Communities concluded thatforeconomic andcultural reasons such
asthese, thedecision onwhere tosetthelevel ofprotection wasnotapurely scientific one,andit
wasnotonewhich could besubject tointernational rules, given thegreat diversity among Members.
TheEuropeanCommunitiesarguedthatthe"appropriatelevel"amemberdecidedtoapplyinitsterritory
didnothavetobeexpressed inthesame technical fashion, i.e.asanMRL. International practice
andtheSPSAgreement leftthischoice totheMember concerned asamatter ofpolicy. Thus, amember
might decide instead ofimposing astricter MRL toprohibit altogether theuseofthesubstance inthe
firstplace, ifthiswastheonly"reasonably available alternative taking intoaccount technical and
economic feasibility thatachieves itsappropriate levelofsanitary orphytosanitary protection andis
significantly lessrestrictive ontrade". TheEuropean Communities further argued thatitslevel of
82Para. 4.57.
83Canada explained thatthiswasriskcharacterization, asexplained inpara. 4.105.
84Canada submitted thatifthere wasnoprobability thatahazard would cause damage, there wasnoneedforasanitary
measure.WT/DS48/R/CAN
Page48
protection inthecaseofthese hormones when usedforgrowth promotion inother countries wasno
residues inmeatdestined forhuman consumption; itfailed toseewhatwasthedifference between
alevelofprotection setatnoresidues fromalevelofprotection setatzeroMRLs forthesesubstances.
Moreover, itappeared thatCanada hadfixed a"zero" tolerance levelforMGA inhorse meat.
4.121 TheEuropean Communities argued thatthere wasapparently aprofound difference between
Canada anditself onthedefinition oftheconcept ofriskassessment forthepurposes ofArticle 5of
theSPSAgreement. IntheECview, theconcept ofriskassessment wascomposed oftwoparts:
thescientific assessment oftheriskandthemanagement ofthatrisk.Inthemanagement oftherisk,
elements other thanstrict science enter intoconsideration, suchasthose inArticle 5.2. Theterm
"appropriate level ofprotection" appeared inArticle 3oftheSPS Agreement. The
European Communities considered thatthere mustexist"apotential riskforadverse effects", i.e.it
wasimplicit thatinorder toneedalevel ofprotection there must besome hazard against which a
Member needs toprotect. However, thisonlyimplies theidentification ofahazard, notanassessment
oftheprobability thatitwould cause damage. TheSPSAgreement leftMembers freetodefine the
levelofprobability theywanted toassume: thismight range from zerotoinfinite; italsoleftthem
freetodecide thetypeofmeasure theymight choose toensure thatthelevelofprotection theyconsidered
tobeappropriate wasachieved. Theapproach oftheSPSAgreement wasalsoinconformity with
democratic regulatory procedures, where frequently adichotomy wasoperated inthedecision making
process between riskassessment andriskmanagement .Thefirstestablished strictly thescientific basis
forregulatory action. Thesecond (riskmanagement) wastheprocess bywhich thecompetent authority
ofaMember decided whataction totakeinthefaceontheassessment submitted toitbythescientists.
Suchaction wasbased onfactors suchaspublic health andenvironmental protection, relevant legislation
andlegalprecedent, application ofsocial, economic andpolitical values andconsumer concerns. In
ademocratic legislative system, theriskmanagement phase, therefore, expressly recognized the
importance ofsocial value choices.
(i) Articles 5.1and5.2oftheSPSAgreement
4.122 Canada recalled thatArticle 5:1readasfollows:
"Members shallensure thattheirsanitary orphytosanitary measures arebased onanassessment,
asappropriate tothecircumstances, oftheriskstohuman, animal orplantlifeorhealth, taking
intoaccount riskassessment techniques developed bytherelevant international organizations."
Canada emphasized thattheessence ofthisobligation wasthatwhen aMember devised andmaintained
asanitary orphytosanitary measure toattain anappropriate levelofsanitary orphytosanitary protection,
themeasure mustbebased onariskassessment. Inthiscase,theriskassessment would beanevaluation
ofthepotential foradverse effects onhuman health arising from thepresence ofhormone residues
inmeat. Canada claimed thatithadbeenunable tofindanyevidence oftheEuropean Communities
having undertaken anappropriate assessment oftherisktohuman lifeorhealth arising fromthepresence
ofresidues inbeeffrom thesixhormones inquestion. IntheWTO consultations, theEuropean
Communities hadstated thatthework oftheLamming Group constituted ariskassessment fortheir
measures. Referring totheterms ofreference andtheconclusions oftheLamming Group
(paragraph 2.28) Canada recalled thattheGroup hadbeensuspended before itcould render afinal
report onzeranol andtrenbolone (seeparagraph 4.7). Thus, thework oftheLamming Group could
atbestbeconsidered ariskassessment onlyofthethree natural hormones.85Intheabsence ofafinal
report, theEuropean Communities didnotappear tohavebased itsprohibition ontheuseofzeranol
ortrenbolone onanyriskassessment. Even iftheLamming Report constituted ariskassessment for
85Themembers ofthegroup subsequently published anassessment ofzeranol andtrenbolone: seeG.E. Lamming et
al.,"Special Report: Scientific report onanabolic agents inanimal production", Veterinary Record (24October 1987)
p.389.WT/DS48/R/CAN
Page49
thethreenatural hormones, itsconclusions hadbeenthatthesehormones would notpresent anyharmful
effects tothehealth oftheconsumer when usedunder theappropriate conditions asgrowth promoters
infarmanimals. Professor Lamming, theChairman oftheGroup, hadhimself asserted thattheEC
measures could notbebased onthatriskassessment.86Moreover, itwould appear thattheEuropean
Communities hadnever conducted ariskassessment ofMGA. Canada noted thatduring theWTO
consultations, theEuropean Communities hadalsostated thatitwasreviewing itsmeasures, andthat
the1995ECScientific Conference constituted thebeginning ofalongprocess ofre-evaluation. Thus,
theECbanwasnotbased onariskassessment ofthese hormones when usedforgrowth promoting
purposes, andtherequirements ofArticle 5.1hadnotbeenmet.
4.123 TheEuropean Communities responded thattheSPSAgreement required Members totake
intoaccount riskassessment techniques developed byrelevant international organizations; however,
Codex wasfarfromdeveloping anysuchtechniques asitwasstilltrying toagree ondefinitions. The
European Communities recalled that"assessment oftherisk" wasdefined inAnnex AtotheSPS
Agreement asfollows: "theevaluation ofthepotential foradverse effects onhuman oranimal health
arising from thepresence ofadditives, contaminants, toxins ordisease causing organisms infood,
beverages orfeedstuffs". TheEuropean Communities noted thattherewere, therefore, threedifferent
concepts todistinguish: the"adverse effect", the"risk" andits"assessment". Forassessing therisk,
Article 5.2provided that:
"Membersshalltakeintoaccountavailablescientificevidence,relevantprocessesandproduction
methods; relevant inspection, sampling andtesting methods; prevalence ofspecific diseases
orpests; existence ofpest-or disease -free areas; relevant ecological andenvironmental
conditions; andquarantine orother treatment."
4.124 TheEuropean Communities argued thattheconcept of"riskassessment ",intheSPSAgreement
waspredominantly ascientific process. Itspurpose wastoestablish thestrictly scientific basis for
theregulatory measure theMember would take. There wasapparently aprofound difference between
Canada andtheEuropean Communities onthedefinition oftheconcept ofriskassessment forthe
purposes ofArticle 5.IntheviewoftheEuropean Communities, theconcept ofriskassessment was
composed oftwoparts: thescientific assessment oftheriskandthemanagement ofthatrisk.Inthe
management oftherisk,elements other thanstrict science entered intoconsideration, suchasthose
mentioned above inparagraph 2ofArticle 5.Moreover, theSPSAgreement didnotprescribe a
quantitative riskassessment. Ariskassessment might helpinsetting astandard designed tolimitthe
probability thatahuman developed cancer afteralifetime ofexposure toaparticular chemical substance
tonomore thanonechance inamillion (1/1,000,000 chance). Bycontrast, thechoice ofthe
1/1,000,000 goal,asopposed to1/1,000 or1/100 orzerochance, wasachoice ofpublic policy (not
ofscientific nature). Thephrase "asappropriate tothecircumstances" intheECviewmustreferto
the"circumstances" oftheMember carrying outtheriskassessment. InthecaseoftheEuropean
Communities, assessment ofriskwaspartofthecomplex EClegislative process, withitscomprehensive
consultations, checks andbalances involving aproposal bytheECCommission, theopinions ofthe
Economic andSocial Committee andtheEuropean Parliament, andtheadoption bytheCouncil of
Ministers.
4.125 TheEuropean Communities disagreed withCanada 'saccount ofthearguments oftheparties
during theconsultations. Itstressed thattheriskassessment carried outforECDirectives 81/602,
88/146 and96/22 hadbeenbased onfollowing scientific evidence:
86G.E.Lamming, "Anabolic Growth Promotants andtheEEC" (Address given attheTechnical Services Centre, Kingston,
ACT, 29April 1986) [unpublished], p.11.WT/DS48/R/CAN
Page50
(i) the1982ReportoftheScientificVeterinaryCommittee,ScientificCommitteeforAnimal
Nutrition andtheScientific Committee forFood onthebasis oftheReport ofthe
Scientific Group onAnabolic Agents inAnimal Production (the"Lamming Report");
(ii) the1983 OIEScientific Conference Report;
(iii) the1987 JECFA Report;
(iv) various works ofrelevant international institutions, suchastheInternational Agency
forResearch onCancer (IARC);
(v) scientific works byindividual scientists relevant totheissue ofuseofhormones in
general andforanimal growth inparticular; and
(vi) information ontheuseofthese hormones forgrowth promotion available fromother
countries, when relevant.
4.126 Fortheadoption ofDirective 96/22 of29April 1996, the1995 ECScientific Conference
Proceedings hadalsobeentaken intoaccount. Allthese scientific data,reports, papers, conferences
andother relevant information constituted abody ofscientific evidence which hadbeencarefully
considered bythecompetent ECinstitutions andbyECmember States. Furthermore, fortheadoption
ofDirectives 81/602/EEC, 88/146/EEC and92/22/EC, apart from theabove scientific evidence,
additional scientific andtechnical information hadbeen taken intoaccount. Thisinformation (see
paragraphs 4.14, 4.19and4.20) consisted mainly oftheinternal studies oftheECCommission, the
reports oftheEuropean Parliament, thereports oftheEconomic andSocial Committee andthe
deliberationsoftheCouncilofMinisters.Fortheirdeliberations,theMinisterswereassistedbyscientific
groups andindividual scientific experts, including experts fromtherelevant administrations oftheEC
member States.
4.127 Thecompetent ECinstitutions hadperformed ariskassessment inthesense ofArticles 5:1
to5:6oftheSPSAgreement bytaking intoaccount theavailable scientific evidence ofriskstohumans
andanimals; relevant processes andproduction methods; andrelevant inspection, sampling andtesting
methods. These latter twoelements confirmed thatriskassessment forthepurposes oftheSPS
Agreement wasnotapurely scientific matter; thepracticalities ofactual application mustalsobetaken
intoaccount.
4.128 TheEuropean Communities observed thatnoneoftheavailable scientific reports hadconcluded
infavour ofanunqualified useofthesehormones foranimal growth promotion. Some ofthesereports
hadconcluded thatallofthesehormones individually werenotlikely toposeriskstohuman oranimal
health, ifusedinaccordance withgoodagricultural/animal husbandry/veterinary practice. However,
other reports hadconcluded thatallofthese hormones weredangerous tohuman andanimal health,
ingeneral aswellaswhen usedforgrowth promotion, andthatnoMRLs could beeasily applied because
theywere carcinogenic.
4.129 The1982and1987Lammingreportsandthe1987JECFAReporthadnotexaminedthepotential
risksarising fromthesehormones when usedincombination withotherhormones, andhadnotexplained
whatconstituted goodagricultural/animal husbandry practice. Forexample, the1982Lamming Report
drewtheattention oftheECCommission totheneedtolaydown certain essential provisions asregarded
thecontrol ofuse:WT/DS48/R/CAN
Page51
"(a) Instructions foruse:
(i) specification ofthedoses, thetypeofpharmaceutical preparation, thenumber
andfrequency ofadministrations;
(ii) association ofanabolic agents;
(iii) localization ofimplant andablation ofzonetreated;
(iv) withdrawal period before slaughter;
(v) identification ofanimals treated, withindication oftheperiod oftreatment.
"(b) Surveillance programme andanalysis methods
(i) control ofproduction andtrade inanabolic agents;
(ii). veterinary control ofauthorized uses;
(iii) means andmethods ofcontrol."
4.130 TheECCommission hadexamined thispossibility in1984, when ithadproposed toallow
theuseofthethree natural hormones forgrowth promotion purposes, under thefollowing conditions
tosafeguard public health andconsumer interests:
(i) products tobeonanEClist,setting outconditions ofuse;
(ii) products must beshown tobeeffective andsafe;
(iii) administration onlybyimplant inapartoftheanimal discarded atslaughter;
(iv) identification oftreated animals, toallow control ofthewithdrawal period;
(v) administration onlybyaveterinarian, withalltreatments recorded;
(vi) meatproduced from treated animals tobeidentified assuchtothefinalconsumer.
4.131 Thisproposal hadbeenfullydiscussed butrejected ontheadditional grounds thatitwasnot
technically oreconomically feasible. Thefollowing objections hadbeenraised:
Cost: Itwould besoexpensive torestrict thesupply andadministration ofhormone growth
promoters byveterinarians thatthecosts would outweigh thebenefits.
Control: Duetothescale oflivestock production andthefactthatimplantation ofgrowth
promoters mustbeperformed atcertain restricted times ofthegrowth period, itwould betechnically
impossibletoensureatalltimes,atreasonableadministrativeandeconomiccosts,aproperadministration
ofhormones.
Bureaucracy:Therecordingofthetreatmentofindividualanimalsandtheircheckingatslaughter
forthepresence ofimplants (toensure theyhadbeencorrectly administered) would beaheavy and
expensive bureaucratic burden andwould further addtothecostoftheprocess.
Inspection: Theinevitable failure tofindremnants ofimplants atslaughter insome animals
(duetomigrationfromtheimplantsite,ormal-administration)wouldentailfurtherexpensiveexamination
andresidue testing, adding further tothecost. Residue testing would ofcourse include thesametesting
andcorrespondingcostsforthird-countrymeatimportedintotheEuropeanCommunities,astheEuropean
Communities would notbeable,intheabsence ofinternationally agreed rulesoncontrols andtesting,
thewidely diverging practices ofMembers, andtheobvious andpowerful economic incentives forWT/DS48/R/CAN
Page52
meat producers todisregard therules, torelyalways ontesting andcontrols carried outbythird
countries.
Labelling: Theinstallation andcontrol ofalabelling system toensure integrity ofidentification
from theliveanimal through slaughter andprocessing toameat product would alsobeextremely
expensive andlaborious. Thecostwould havetobeborne bytheproduct, which again would render
thewhole process uneconomic. Furthermore, retail premises, including restaurants, which supplied
unwrapped meat directly totheconsumer would havetocarry aprominent warning thattheyused
meatfrom animals treated withhormones. Thiswould beastrong disincentive tousing suchmeat
andwould thusamount toarestriction ontrade. Inaddition, consumers would havenocontrol and
would notbeabletomake reliable authentic choices (e.g.ofmeatserved inrestaurants).
Forthesereasons, ithadbeenconcluded thatabanontheuseofhormones forgrowth promotion would
belesstrade-restrictive thantheimposition ofthecontrol system which would otherwise berequired.
TheEuropean Communities argued that,therefore, ithadbased itsmeasures ontheriskassessment
ithadconducted forthatpurpose.
4.132 Canada claimed thatbyincluding under the"appropriate circumstances" ofArticle 5.1"...the
complex EClegislative process, withitscomprehensive consultations, checks andbalances involving
aproposalbytheECCommission,theopinionsoftheEconomicandSocialCommitteeandtheEuropean
Parliament, andtheadoption bytheCouncil ofMinisters", theEuropean Communities contradicted
itsownobservation thatthepurpose ofariskassessment "...istoestablish thestrictly scientific basis
fortheregulatorymeasuretheMemberwouldtake..."andconfusedtwodistinctaspectsofriskanalysis:
riskassessment, andriskmanagement. The"complex EClegislative process" wastheriskmanagement
phase -theprocess ofweighing policy alternatives inlightoftheresults ofriskassessment and,if
required, selecting andimplementing appropriate control options, including regulatory measures. It
wasnotpartoftheriskassessment. InCanada 'sview, thephrase "asappropriate tothecircumstances"
referred tothestateofscientific andtechnical knowledge intheareaofconcern.
4.133 Canada claimed thattheECmeasures werenotbased onanappropriate riskassessment. In
thiscase, theriskassessment would beanevaluation ofthepotential foradverse effects onhuman
healtharisingfromthepresenceofhormoneresiduesinmeat.TheEuropeanCommunitieshadidentified
cancer astheadverse effect fromwhich theECmeasures purportedly protected humans. InCanada 's
view, theEuropean Communities tookaveryselective approach oftheevidence upon which itsaid
ithadbased itsriskassessment inpointing topurported gapsintheconclusions, characterizing the
conclusions asmore tentative thantheytrulywere, andignoring theneedforascientific basis forits
measures.
4.134 Canada stressed thatthe1987 Lamming Report unequivocally stated that: "The levels of
trenbolone andzeranol andtheirmajor metabolites found inedible tissue, following accepted husbandry
practices, aresubstantially below thehormonally effective doses inanimal testsandtherefore donot
present aharmful effect tohealth "87(emphasis added). TheLamming Group hadalsoclearly stated
thatithadexamined allthestudies available "including bothlongtermcarcinogenicity studies and
shorttermtests", andtheinformation onwhich ithadbased itsworkwasamply referenced inthereport.
Finally, itwasgenerally accepted bythescientific community thatthecarcinogenicity ofthesehormonal
substances wasindeed related totheirhormonal effect. Canada stated thatnoneofthe"sources of
evidence" identified bytheEuropean Communities haddetermined that,atthelevels usedforgrowth
promotion incattle, thesixhormones atissue posed arisktohuman health. Inparticular, nonehad
determined thattheywould cause cancer inhumans consuming meatcontaining theresidues ofsuch
hormones.
87G.E. Lamming etal.,"Special Report: Scientific report onanabolic agents inanimal production," (24October 1987),
Veterinary Record, p.389.WT/DS48/R/CAN
Page53
4.135 Canada argued thatthere were fourpieces ofevidence todemonstrate thattheEuropean
Communities hadnotbased theirmeasures onanappropriate riskassessment, asrequired byArticle 5.1.
First, theresponse given bytheEuropean Communities astowhytheLamming Group hadbeen
suspended before itcould submit itsreport onthexenobiotics, trenbolone andzeranol, wasthat:
"Itwasdecided bytheCouncil, during thedeliberations ofthesecond Lamming Committee
fortheadditional dataconcerning onlythetwosynthetic hormones, toadopt alevelofprotection
which avoids thepresence ofanyresidues ofadded hormones inmeat."
Thisclearly demonstrated that,theEuropean Communities hadadopted itsmeasures originally without
thebenefit ofacurrent scientific opinion and,therefore, therewasnopretence thatthemeasures were
based onascientific assessment. Indeed, ithadbeensuggested byProfessor Lamming thattheywere
based onpolitical considerations.
4.136 Second,inreplytoaquestiononthesourcestheyrelieduponfortheirpurportedriskassessment,
theEuropean Communities hadstated:
"The works ofIARC arewellknown ...Theindividual scientists aresomany tociteallof
them. Initssubmissions, theEChasreferred tothe1983 OIEConference Report, the1995
ECConference report, theworks byDr.R.Hertz, S.S.Epstein andJ.Liehr ..."
Canada argued thattheworks ofIARC, the1983 OIEConference, andthe1995 ECScientific
Conference report didnotsupport theECposition. Inaddition, theEuropean Communities hadrefused
toclarify theirreliance ontheworks ofindividual scientists. Dr.Hertz hadbeenonlymentioned in
theECsubmissions inthereports ofother authors. These werehardly the"works" ofDr.Hertz; they
were theworks ofothers.
4.137 Third, Canada noted thattheEuropean Communities 'terms ofreference foranopinion obtained
fromDr.Liehr made itclearthatthere wasnoreliance ontheworks ofDr.Liehr atthetimetheEC
measures came intoeffect -evenforthemost recent revision (Directive 96/22/EC). Theletter to
Dr.Liehr, provided bytheEuropean Communities, stated inpart,asfollows:
"The scientists employed bytheECtellmethatyouareprobably oneoftheveryfewleading
scientists inthisareaofexpertise world-wide who, having carried themselves research fairly
recently, suggest thatthenatural hormones andinparticular their metabolites (i.e.
catecholestrogens-metabolites ofnatural hormone oestradiol-17 )are,contrary tothegenerally
heldview, genotoxic andhence under certain conditions theymaycause (notonlypromote)
thegenesis oftumours. Ifthisiscorrect, wethenunderstand thatnotolerance levels canbe
established forpotentially genotoxic substances, asitwasthecaseinthepastforexample with
DES.
"Iftheabove information iscorrect, thiswould beveryvaluable scientific information forthe
ECandofcourse theGATT Panel totakeintoaccount. Inaway,itwould justify theEC's
cautious approach against theuseofthese hormones forgrowth promotion ,aspotentially
carcinogenic substances irrespective ofthedoseandtheconditions under which theymaybe
administered toanimals forgrowth promotion" (emphasis added).
Canada argued thattheEuropean Communities weresearching, expostfacto,forascientific justification
foritsmeasures. Indeed, inperforming itsriskassessment ofoestradiol-17 todetermine whether
aMRL would berequired under Regulation 2377/90, theEuropean Communities didnotsubscribe
toDr.Liehr'stheory ofgenotoxicity. Rather, theECpublic summary stated, "...itisconcluded thatWT/DS48/R/CAN
Page54
thetoxic effects including carcinogenicity occur asanextension ofthephysiological effects of
oestradiol".88Canada recalled too,thatoneoftheECexperts, Dr.Bridges, hadasserted thatthe1995
ECScientific Conference didnotlookatgenotoxicity because itwasnotofcurrent concern. Canada
wondered, howcould theissue ofgenotoxicity figure solargely intheriskassessment ofameasure
passed inApril 1996, when theECscientists attending theNovember-December 1995Conference did
notthink itwasaparticularly important issue?
4.138 Canada argued thatDr.Liehr'sterms ofreference alsorevealed thattheEuropean Communities
werenotinterested inanobjective opinion onthecarcinogenicity ofthehormones atissue. Theterms
ofreference stated:
"Provided weunderstand correctly theconclusions ofthescientific research carried outby
yourand/your co-scientists ,theEuropean Communities would beinterested inrequesting from
youawritten scientific opinion dealing withthefollowing questions:
-Arethethree natural hormones (oestradiol-17 ,testosterone andprogesterone) or
theirmetabolites potentially genotoxic?"
Canada suggested thattheEuropean Communities hadgonesofarastoaskDr.Liehr tofindfault
withtheJECFA report soastojustify theECdeparture from theinternational standards:
"Ifyoufeelthatthefollowing twoquestions alsofallwithin yourfieldofexpertise, Iwould
alsoappreciate areply:
-...whatiswrong from abroad scientific point ofviewwiththe1988 FAO/Codex
Alimentariusexpertgroupreport?Onwhatprecisescientificgroundscouldyoucriticize
it?"
Canada submitted thattheopinions ofexperts retained bytheEuropean Communities lacked objectivity
andshould beconsidered accordingly.
4.139 Fourth, Canada argued, were theECevaluations ofoestradiol-17 andprogesterone under
Regulation 2377/90 (which required review ofthethree natural hormones permitted fortherapeutic
use). None ofthese hormones hadbeenplaced inAnnex IV(listofsubstances forwhich noMRL
canbefixed). Oestradiol-17 hadbeenplaced inAnnex II(listofsubstances notsubject toMRLs).
Foroestradiol, theECpublic summary report stated: "...oestradiol doesnotinduce genemutations
invitro,butconflicting results arefound inchromosomal aberration assays. Following longterm
exposure theincidence oftumours intissues withhighlevelofhormone receptors isincreased (e.g.
mammary tumours). Itisconcluded thatthetoxiceffects including carcinogenicity occur asanextension
ofthephysiological effects ofoestradiol ...".89
4.140 Inconsidering inclusion ofprogesterone inAnnex II,theEuropean Communities stated inthe
public summary report:
"According totheInternational Agency forResearch onCancer (IARC), progesterone does
notexhibit mutagenic activity inmost invitroandinvivotestsperformed, butisknown to
increase thetumour incidence inendocrine target tissues (ovaries, uterus, mammae) after
continuous (parenteral) doses clearly above thephysiological levels. Progesterone isnot
carcinogenic perse,butactsviaanepigenetic mechanism associated withitsendocrine activity,
88Para. 3ofthepublic summary, cited byDr.Arnold, answer toPanel question 5,para. 6.54.
89Ibid.WT/DS48/R/CAN
Page55
i.e.itsability tocause ahyperproliferative effect atcellular levels mediated bysteroid-hormone
receptor interaction. Hence, tumours willnotresult fromingestion ofprogesterone atlevels
thatdonotproduce anyhormonal effects."90
Furthermore, thepublic summary stated that,"[a]stheresidue studies showed thatthemilk, tissue
andplasma levels aftertherecommended treatment withprogesterone wereatorwithin physiological
limits, theconclusion ofJECFA thatnoADIorMRLs forprogesterone needtobeestablished can
alsobeadopted forthetherapeutic andzootechnical useofprogesterone".91
4.141 Thus,Canadanoted,theEuropeanCommunitiesitselfhadmadetheassessment,underRegulation
2377/90, thatthenatural hormone oestradiol-17 wassafetouse.Asimilar review ofprogesterone
hadreached thesameconclusion. TheEuropean Communities continued toallow theuseofoestradiol-
17andprogesterone fortherapeutic andzootechnical purposes and,thus, hadchosen tocontinue to
expose ECconsumers toresidues ofthese substances. Canada argued thatitwassimply incongruent
fortheEuropean Communities tomaintain thatitsriskassessments haddetermined thatthewidespread
useofthese substances forzootechnical purposes wassafe,whereas theiruseforgrowth promotion
wasnot.
4.142 TheEuropean Communities observed thatCanada didnotappear toargue thatthechallenged
measures hadnoscientific basis, butthattheywerenotbased onanappropriate riskassessment. Canada
apparently believed thattheonlyacceptable evidence ofriskassessment inthiscase, onwhich the
European Communities should havebased itsmeasures, weretheLamming Reports of1982and1987
andthe1987 JECFA Report. However, intheEuropean Communities 'view, neither the1982 and
1987Lamming Reports northeJECFA Report constituted inthemselves "riskassessment" inthesense
ofArticles 5.1to5.6ofSPSAgreement. They onlyformed partof"available scientific evidence".
Theother factors mentioned inArticle 5.2andinparagraphs 3to6thereof, were notdealtwithby
theabove scientific reports. Theassessment ofthese factors wasnotascientific question inthestrict
sense, andthustheyfellwithin theresponsibility oftheappropriate political authorities ofeachMember.
4.143 TheEuropean Communities weresurprised bytheinterpretation made byCanada ofthewords
contained inArticle 5.1"asappropriate tothecircumstances". Ifthese words meant "thestateof
scientific andtechnical knowledge intheareaofconcern", theremaining phrase inArticle 5:1"taking
intoaccount riskassessment techniques developed bytherelevant international organizations" would
serve nouseful purpose. Thephrase "asappropriate tothecircumstances" wasfrequently usedin
legaltextsandusually required, ashere, tobring close totheconcrete circumstances ofapplication
theconcept under examination. Inthiscase, theriskassessment should takeintoaccount thenature
ofthesubstances andthetypeofriskstheyposed tohuman andanimal health intheterritory ofeach
Member. Asubstance might notbeviewed asposing veryserious risksinacountry, e.g.,salmonella
inSouth Africa, whereas thesame substance might beviewed asposing aserious risktohumans in
theEuropean Communities (andforthatreason theEuropean Communities hadtaken drastic measures
tomake surethatitwascompletely eradicated initsterritory). Another example might bethatsome
partsofthepopulation ofaMember might beviewed tobeexposed todifferent degrees, either higher
orlower torisksfrom acertain substance andthere might stillbeother parts ofthepopulation (e.g.
young children) which were more vulnerable toacertain typeofriskthanothers. Allthese were
circumstances which needed tobetaken intoaccount byaMember when assessing arisk.
4.144 TheEuropean Communities stressed thatthere didnotexistyetriskassessment techniques
developed bytherelevant international organizations. Codex wasstilldiscussing different concepts,
butthere wasnoagreement yetonthese techniques. AMember was,therefore, freetomake an
90Ibid.,p.12, para. 9ofthepublic summary.
91Ibid.,para. 16ofthepublic summary.WT/DS48/R/CAN
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assessment oftheriskasitthought correct andaswasappropriate tothecircumstances prevailing in
itsterritory. Canada 'sdefinition ofthephrase "asappropriate tothecircumstances" would devoid
itofanyuseful meaning. Article 5.2laiddown theelements aMember should takeintoaccount in
anassessment oftherisk: available scientific evidence, relevant processes andproduction methods,
relevant inspection, sampling andtesting methods, prevalence ofspecific diseases, etc.Each ofthe
three words "available scientific evidence" hadadistinct meaning: theevidence aMember tookinto
account foritsriskassessment hadtobescientific, i.e.itmusthavetheminimal attributes ofscientific
inquiry, anditshould bepartofthebody ofscientific knowledge intheareaofconcern, evenifit
wasnottheprevailing viewamong scientists.
4.145 Thisconcept of"available scientific evidence" wasalsoconfirmed bythedefinition oftheterm
"scientific justification" given inthefootnote ofArticle 3.3,where itwasexplained thatthere was
"...scientific justification ifonthebasis ofanexamination andevaluation ofavailable scientific
information ...aMember determines ...".Forsystematic purposes, theconcept ofscientific evidence
intheSPSAgreement could nothavedifferent meanings initsvarious provisions. There wasapparently
aprofound difference between Canada andtheEuropean Communities onthedefinition oftheconcept
ofriskassessment forthepurposes ofArticle 5.IntheviewoftheEuropean Communities, theconcept
ofriskassessment wascomposed oftwoparts: thescientific assessment oftheriskandthemanagement
ofthatrisk.Inthemanagement oftherisk, elements other thanstrictly science entered into
consideration, suchasthose mentioned above inArticle 5.2.TheEuropean Communities argued that
inthePanel proceedings anumber ofexperts advising theEuropean Communities hadexplained their
views onthepotential dangers tohuman andanimal health fromtheuseofthese hormones forgrowth
promotion. However, noneoftheexperts advising thePanel hadargued thattheexperts referred to
bytheEuropean Communities didnotemploy scientific principles intheirresearch. Article 2.2of
theSPSAgreement didnotrequire thebestscience northeweight ofscientific evidence tobetaken
intoaccount; itonlystipulated thatthereshould be"scientific principles" and"sufficient" (notabsolute)
scientific evidence. Forexample, Dr.Lucier hadagreed withtheconclusions oftheECscientists
thatboththenatural andsynthetic hormones were carcinogenic atlowlevels (thenatural hormones
werecarcinogenic evenatexisting physiological levels). Some ofthescientists whoattended themeeting
ofexperts (andthose ofJECFA 1988) might notagree withtheconclusions ofthescientists advising
theEuropean Communities. Butthiswasnotrelevant forthepurposes ofArticle 5.2,2.2and3.3
oftheSPSAgreement. What wasimportant waswhether, inthescientific research employed bythe
ECscientists (orthescientific reports towhich theymade reference intheirreports), theminimal
attributes ofscientific inquiry wererespected. TheEuropean Communities hadnotheard theopposite
fromanyoftheexperts advising thePanel norfromCanada. Therefore, theEuropean Communities
wasallowed totakeintoaccount itsscientific views (ortheviews ofthescientists towhich theyreferred
intheirreports) initsassessment oftherisksofthese hormones forgrowth promotion.
4.146 TheEuropean Communities argued thatthefirstECDirective dated from1981andthesecond
from1988. Theprohibition ontheuseofthesehormones forgrowth promotion hadentered intoforce
on1January 1989. Atthattime, there were noCodex standards forthese hormones. TheJECFA
reports werebased onscientific evidence dating from some years before 1988, whilst newscientific
evidence started toemerge around 1985suggesting thatthese hormones weredangerous tohuman and
animal health because theywere carcinogenic. Butaswithanynewdiscoveries, ithadtaken time
forthese newscientific views togetestablished inthescientific community. Inviewofthatscientific
uncertainty, theEuropean Communities haddecided nottofollow theweight ofscientific evidence
underlying theJECFA reports forthefivehormones. Thedoubts oftheEuropean Communities on
theweight ofthescientific evidence wereexplained inthepreparatory work ofDirective 88/146 and
thediscussions intheEuropean Parliament, theEconomic andSocial Committee andtheCouncil of
Ministers. Theso-called Collins reports and,inparticular, thePimenta reports, established clearly
thattheEuropean Parliament hadheard averylarge number ofscientists before issuing itsreports.
Itappeared thatinCanada 'sview, riskassessment could onlybeperformed byanumber ofscientists
formally getting together andissuing aformal report within aninstitutionalized system, likeJECFA.WT/DS48/R/CAN
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Other scientific views notreflected inthatreport didnotseem tobeconsidered byCanada toform
partofthescientificevidence.TheEuropeanCommunitiesdidnotacceptthisconceptofriskassessment.
TheSPSAgreement didnotprovide rulesonhowtheriskassessment should bedone; itonlyindicated
theelements thatshould betaken intoaccount. Until suchtechniques weredeveloped, eachMember
wasfreetodecide foritself theprocedures itused forassessing therisks inanycase. The
European Communities haditsownsystem ofriskassessment, where there wasconstant interaction
between thescientific committees andexperts advising theCommission, theEuropean Parliament and
theCouncil ofMinisters. Itmight takesome timetobecompleted, butthatwasitssystem ofrisk
assessment.
4.147 TheEuropean Communities further argued thatastwooftheexperts advising the
EuropeanCommunities,Dr.LiehrandDr.Adlercreutz,hadshownintheirreports,mostofthescientific
evidence onthecarcinogenic effects ofthese hormones wasbased onnewresearch andtoxicological
methods which hadstarted toappear aftertheissuance ofthe1988 JECFA report. Toconsider the
1988JECFA report asrepresenting thestateoftheartonthehazards tohuman andanimal health from
theuseofthesehormones forgrowth promotion would amount tovoluntarily ignoring thenewscientific
progress inthename ofregulatory stability. Totakethefixed viewthatonlythe1988 JECFA report
could contain scientific truths onthehazards posed bythese hormones, asargued byCanada, was
scientifically absurd. Asregarded thecriteria forinclusion ofsubstances intoAnnex IIofECRegulation
no.2377/90, theEuropean Communities underlined thatinaddition tothescientific assessment ofthe
risk,asubstance might beputinAnnex II(where noMRLs wereestablished) iftheanimals inquestion
werenotsentforslaughter immediately aftertherapeutic orzootechnical treatment. Animals treated
fortherapeutic orzootechnical purposes were notslaughtered forhuman consumption. After such
treatment wasperformed, ittooksome timebefore theveterinarian conducting thetreatment discovered
whether thetreatment waseffective ornot. Ifaftersome time, depending ontheanimal andthe
therapeutic orzootechnical treatment performed, theveterinarian discovered thattheanimal could not
bemaintained asabreeding animal, thepossibility ofslaughtering wasconsidered. Butthismeant
thatinaddition tothestrict conditions imposed byEClawforsuchtreatment, there wasalapse of
timebetween suchtreatment andthepossibility ofslaughtering. Thepercentage ofanimals receiving
suchtherapeutic orzootechnical treatment andwhich might beslaughtered didnotrepresent more than
1percentoftotalbovine animals usedforhuman consumption intheEuropean Communities. This
lowpercentage, along withtheconditions imposed fortreatments andthetimelapsed before possible
slaughter, guaranteed thatthere would benoresidues ofoestradiol 17leftinmeatusedforhuman
consumption. Therefore, thelevelofprotection oftheEuropean Communities inthiscasewasnot
affected atall.
4.148 TheEuropeanCommunitiesclaimedthatitwasnecessarytoavoidtheapparentconfusionbetween
theterms "adverse effect", "risk", "riskassessment", "level ofprotection achieved bymeasures based
ontherelevant international standards", and"appropriate levelofprotection determined byaMember".
Noting thatithadexplained indetail the"risk" (i.e.the"potential foradverse effects onhuman and
animalhealth")fromtheuseofhormones(seeparas.4.144andff.),theEuropeanCommunitiesindicated
thatthe1988 JECFA report hadalsofound thatthere wasapotential risktohuman health: ifthere
werenosuchpotential risk,JECFA would havenotrecommended ADIs andMRLs forthetwosynthetic
hormones. Forthethreenatural hormones the1988JECFA report didnotrecommend ADIs andMRLs
essentially because ofproblems indetecting thelevelofresidues inthemeatonaroutine basis. Scientists
hadsaidthat"theADI-model isnotariskmodel anddoesnotpredict theriskoftheoccurrence of
adverse effects, when ADI-values areexceeded"92.Thesame wastruebasically fortheMRL-model,
"which specifies thequantity ofaparticular residue inmeatthat,evenindietary extremes, would not
exceed theADIfortheparticular substance concerned."93So,theMRL wasbased onthenotion that
921995 ECScientific Conference Proceedings, p.375.
93Ibid.,p.4.WT/DS48/R/CAN
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therewasarisk,butiftheproposed threshold wasobserved theprobability oftheadverse effect arising
from theuseofhormones would notmaterialize. Clearly, inthiscasewhatthe1988 JECFA report
haddonewastorecommend standards which would achieve "alevelofprotection" against thepotential
risksfromtheuseofhormones. ButtheSPSAgreement allowed Members todetermine another level,
i.e.theleveltheydeem appropriate. Thislevelmight behigher orlower.
4.149 Canada claimed thattheSPSAgreement didnotdefine theterm"risk". However, itsmeaning
could bededuced from thedefinition of"risk assessment". Reduced toitscomponents, riskwasthe
potentialforadverseeffectsonhumanoranimalhealtharisingfromcertainsources,namelythepresence
ofadditives, contaminants, toxins ordisease causing organisms infood, beverages orfeedstuffs.
Assessment wastheevaluation ofthatpotential. Canada submitted that,inthiscase, theonlysource
ofriskwould bethepresence ofhormone residues, including theirmetabolites, inthemeatfromanimals
treated withthesixhormones atissue. Contrary totheECarguments, problems linked tothe
administration ofhormones, thedetection andcontrol ofhormone residues inmeat, andsoforth, were
notsources ofrisk;i.e.,theydidnotfallwithin "...thepresence ofadditives, contaminants, toxins
ordisease causing organisms infood, beverages orfeedstuffs".
4.150 TheEuropean Communities contended thatavailable scientific evidence showed theuseof
thenatural andsynthetic hormones subject tothisdispute could bedangerous tohuman andanimal
health. Thepotential danger resulted from(i)theirnature andmode ofaction; (ii)theaction oftheir
metabolites; (iii)combinations ofhormones andmultiple exposure; (iv)problems linked totheir
detection andcontrol; and(v)problems linked totheiradministration. Insubmitting itssupporting
arguments, theEuropean Communities indicated thatitfocused onthepotential riskstohuman beings,
butthatthisdidnotimply thatthere were norisksforanimal health.
(i) Thenature andmode ofaction ofhormones
4.151 TheEuropean Communities claimed thateven though theprecise mode ofaction ofthe
hormones atissue hadonlybeenpartly understood, allscientists agreed thatthese hormones were
dangerous. Acharacteristic ofhormones wastheirextreme potency. They wereproduced inminute
quantities, often atasitedistant fromtheirtarget sitebutproduced significant effects. Hormones had
awiderange ofactions which affected almost allsystems ofthebody. Theprinciple sexhormone
inmen,testosterone, contributed toacne, baldness, prostatic disease, coronary heartdisease andpeptic
ulceration. Oestrogens, andtoalesser extent progesterone, exposed women topremenstrual tension,
dysmenorrhoea, some disorders ofthereproductive system andanincreased tendency todevelop
gallstones. More importantly, thesehormones alsoplayed amajor roleinthedevelopment oftumours
insex-hormone dependent tissues (forexample prostatic cancer, breast cancer, cancer oftheuterus
andneoplastic liverdisease).
4.152 TheEuropean Communities noted thatthecarcinogenic risksfromthese hormones werewell
known. Forinstance, inthe1983 OIEScientific Report ascientist hadconcluded that"although it
isunlikely thatthesmall amounts ofanabolic steroids which might beingested inagricultural produce
could (cause cancer), thispossibility should notbeignored entirely" (page 274). Moreover, thesame
1983 OIEScientific Report stated that:
"...Itisdifficulttobeentirelyconfidentaboutpredictingandassessingthetoxicandcarcinogenic
effects ofanyphysical orchemical agent, butinbalancing risksandbenefits available evidence
strongly favours theviewthatresidues ofanabolic agents present inagricultural produce do
notpresent anyhazard tothehuman population provided thatadministration ofthese agents
isproperly controlled andthattheresearch fornewagents continues "(page 284).
TheEuropean Communities argued thatthispartoftheOIE1983 Report hadnowproven tobethe
most correct prediction ofthemode ofaction andpotential toxic andcarcinogenic effects oftheseWT/DS48/R/CAN
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hormones. Thiswasinparticular thecaseforoestradiol-17 andtheother twonatural hormones,
which untilrecently wereamong those thought tobethemostsafetoadminister toanimals andhumans.
4.153 The1987 IARC Report indicated that,inthecaseofandrogens:
"Thefactthatcastration palliates prostatic cancers suggests thattestosterone maybeinvolved
inthegenesis ofthese tumours, andanumber ofepidemiological observations suggest that
increased testosterone levels mayincrease theriskforprostatic cancer" (page 96).
"Theevidence thatanabolic steroids cancause bothbenign andmalignant livertumours isquite
strong .However, because noanalytical epidemiological study hasbeendone, theWorking
Group feltconstrained toclassify theevidence forcarcinogenicity inhumans asnomore than
"limited" (page 97).
Inthecaseofoestrogens, however:
"Anumber ofstudies, utilizing avariety ofdesigns, haveshown aconsistent, strongly positive
association between exposure toanumber ofoestrogenic substances andriskofendometrial
cancer ,withevidence ofpositive dose-response relationships bothforstrength ofmedication
andduration ofuse"(page 280).
4.154 TheIARC didnotdifferentiate between theeffects ofthesubstance athighdoses versus low
doses, asregards theevidence concerning androgenic anabolic steroids. Asregards oestrogens,
progestins andcombinations thereof (i.e.mainly oestradiol-17 ,progesterone andMGA), the1987
IARC Report explained:
"Steroid hormones areessential forthegrowth, differentiation andfunction ofmany tissues
inbothanimalsandhumans.Ithasbeenestablishedbyanimalexperimentationthatmodification
ofthehormonal environment bysurgical removal ofendocrine glands, bypregnancy orby
exogenous administration ofsteroids canincrease ordecrease thespontaneous occurrence of
tumours ortheinduction oftumours byapplied carcinogenic agents ....Theincidence of
tumours inhumans could bealtered byexposure tovarious exogenous hormones, singly or
incombination ."
"These statements make explicit thefactsthatoestrogens andprogestins occur naturally, and
thatthehormonal milieu anddose-effect relationships aregenerally inextricably involved in
thecarcinogenic effects ofoestrogens andprogestins.
"Inthissection, wedescribe thehuman epidemiology, carcinogenicity studies inanimals, and
other relevant dataforoestrogens andprogestins alone andincombination. Thehuman
epidemiological datareflect thepatterns ofuseofoestrogens andprogestins andtheir
combinations inmedical practice, i.e.,theavailable information concerns specific products
usedforparticular indications. Although mayoftheproducts havethesame constituents (or
asimilar classofconstituents), doses varyamong products andthecompounds anddoses have
changed overtime. Theoperating principle istodetermine theability ofthechemical toproduce
cancer orother genetic andrelated effects without thestrictures ofmode ofhuman useorthe
magnitude ofthedoses. Thus, there isabasic incongruity between thehuman dataandthe
animal carcinogenicity data. Asnoted earlier, however, theeffects ofthesechemicals inhumans
appear, atleastinmostcases, tobelinked tothehormonal milieu "(page 272,emphasis added).
The1987 IARC Report concluded bysaying:WT/DS48/R/CAN
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"There isabasic incongruity between thehuman dataandtheanimal carcinogenicity data.
Asnoted earlier, however, theeffects ofthese chemicals inhumans appear, atleastinmost
cases,tobelinked tothehormonal milieu" (page 272,emphasis added).
TheEuropean Communities submitted thatthephrase "atleastinmostcases" didnotmean, ofcourse,
"inallcases" andunder allconditions. Itfollowed fromtheabove thatthefindings oftheIARC reports
aimatestablishing thecarcinogenic orother effects ofthese substances irrespective ofthemodes of
human useandthemagnitude ofthedoses.
4.155 TheEuropean Communities further noted thatthecarcinogenic effects ofhormones onhumans
(andanimals) hadbeendocumented byseveral reports oftheIARC. IARC hadclassified steroidal
oestrogens(includingoestradiol)inGroup1,meaningtheagentwascarcinogenictohumans;androgenic
(anabolic) steroids (including testosterone) inGroup 2.A,agents probably carcinogenic tohumans and
progestins inGroup 2.Boragents possibly carcinogenic tohumans.94
4.156 There wasabodyofscientists which believed thatthenatural hormones acted bybinding with
highaffinity andhighspecificity toprotein receptors which werepresent inhormone-responsive tissues.
Asaresult ofhormone binding tothereceptor, thereceptor underwent aconformational change, bound
tospecific DNA sequences andregulated theexpression ofspecific genes withacell.95Asregarded
thesynthetic hormones, thereweresomescientists whothought thattheseexerted theirbiological effects
viathehormone-receptor mechanism, buthadalsopharmacokinetic andpharmacodynamic properties
which distinguished them from thenatural hormones. Forexample, most ofthese synthetic agents
hadoralactivity. Tissue distribution wasaltered because ofdifferences intheirrelative binding affinity
forserum transport proteins. These synthetic agents might alsodiffer fromnatural hormones intheir
rateofmetabolism andexcretion.96
4.157 TheEuropean Communities submitted thatthestateofscientific knowledge in1983 onthe
wayallhormones exerted theirbiological action hadbeensummarised asfollows:
"Although many studies havebeenperformed inthisfieldoverthelastfewyears, the
fundamental mode ofaction atthemolecular levelhasnotasyetbeenfullyelucidated."97
4.158 TheEuropeanCommunitiesassertedthatthescientificassumptionthat,despitetheircarcinogenic
potential,thesehormoneswerenotlikelytocauseproblemstohumanhealthwasbasedontheassumption
that"thecarcinogenic effect ofthesehormones isrelated tothehormonal activity ofthesecompounds,
i.e.anincrease intumour incidence intissues ofanimals withhighlevels ofspecific hormone receptors,
which would notoccur atnormal physiological levels".98Butscientists could notdefine what those
"normal physiological levels" were since theconcentrations ofthenatural hormones inthebody of
theanimal varied widely according totheanimal species, thesex,age,breed, season, nutritional status
andthephysiological stateoftheanimal. Asaconsequence, adecision onthe"normal" concentration
94IARC Monographs (1987), Supplement 7,pp.31, 96and280.
95M.A.Miller,J.K.Leighton,"RiskAssessmentStrategiesforHormonesandHormone-likeSubstances",1995ECScientific
Conference Proceedings, p.386.
96Ibid.,p.389.
971983 OIEConference Report, p.54. TheEuropean Communities noted thatinthesame OIEReport (p.233), three
USscientists hadexplained that"...the published dataonoestrogen concentrations inthetissue offoodproducing animals
isscarce. Thenoticeable lackofsuchdatapresents nomore thanadimunderstanding ofoestrogen distribution andmetabolism
inthetissue offood producing animals, such asthecowandpig".
98H.A. Kuiper, "Risk Assessment Strategies forXenobiotics", 1995 ECScientific Conference Proceedings, pp.370-371.WT/DS48/R/CAN
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levelofthese hormones ,i.e.alimitatwhich itwaspossible todecide whether ornotananimal had
beentreated withanatural occurring hormone, wasalmost impossible tomake. Forthese reasons,
these hormones wereconsidered bysome scientists tobe"promoters rather thatprimary inducers of
cancer inhormonally sensitive tissues".99According totheEuropean Communities, itwasonthis
assumptionthatwasalsobasedthe1988JECFAReport,onwhichCodexhadbaseditsrecommendations.
Withregard tooestradiol-17 ,the1988JECFA Report stated that"The results ofstudies ...(showed
that)...Oralandparenteral administration ofoestradiol-17 canincrease theincidence oftumours
inexperimental animals. These tumours largely occur intissues withhighlevels ofspecific hormone
receptors thatarenormally responsive tostimulation bytheparticular hormone concerned. The
Committeeconcludedthatthecarcinogenicresponsewasrelatedtothehormonalactivityofoestradiol-17
atlevels considerably higher thanthose required foraphysiological response"100(page 18).
4.159 TheEuropean Communities contended, however, thatmore recently anumber ofscientists
hadsuggested thatthishormone could beconsidered tobenotonlyapromoter butalsoaprimary inducer
ofcancer atleastinhormonally sensitive tissues101,andthatthe1988JECFA Report wereoutofdate.
4.160 TheEuropean Communities observed, forexample, thatDr.Liehr argued that"oestrogens
havebeenimplicated forsome timeintheinduction ofhuman cancers, andthereisincreasing evidence
ofasimilar roleforprogesterone andtestosterone".102Inparticular, Dr.Liehr hadstated:
4.161 "Inthecaseofoestradiol, experiments haveshown thatitshormonal potency isnot
linked toitscarcinogenic activity. Investigations ofthemetabolic pathways ofoestradiol have
revealed thatfreeradicals arecontinuously produced, andDNA damage bythesefreeradicals,
aswellasDNA adduct formation, hasbeendemonstrated inarange oftissues. Asdamage
toDNA andDNA adduct formation areknown tobeassociated withtumour formation, these
experiments provide strong evidence thatoestradiol isagenotoxic carcinogen. Inthecase
ofprogesterone andtestosterone, itisnotclearwhether theircarcinogenic effects aremediated
bytheiraction onspecific receptors intarget tissues orduetomutagenic DNA damage.
"Inthepresent stateofknowledge, itisverydifficult andinanycasenotadvisable todetermine
asafe threshold dose ofhormone below which tumour formation willnotoccur.
Hormone-associated tumours inthebreast, uterus orprostate maybeinduced byacombination
ofexogenous andendogenous hormones and/or theirmetabolites. Asthetotalamount of
hormone ormetabolite necessary fortumour induction isnotknown, theamount ofexogenous
hormone ormetabolite necessary fortumour induction inaddition tounknown amounts of
endogenous hormone ormetabolite hasnotyetbeendetermined. Inthe1988 JECFA report,
theauthors considered onlythehormonal receptor-mediated activities ofthenatural hormones.
Inviewoftheconsiderableamountofscientificevidencewhichhasaccumulatedsincetherelease
ofthatReport, particularly inrespect ofthegenotoxicity ofoestradiol, theReport cannolonger
beconsidered applicable toariskassessment oftheuseofhormone growth promoters".103
4.162 Inaddition theEuropean Communities argued thatDr.Adlercreutz indicated that:
99H.A.Miller,J.K.Leighton,"RiskAssessmentStrategiesforHormonesandHormone-likeSubstances",1995ECScientific
Conference Proceedings, p.386, and1983 OIEScientific Report, p.339 etseq.
100TheEuropean Communities noted thatthesame assumptions were made inthe1988 JECFA Report forprogesterone
(p.20), testosterone (p.2), trenbolone acetate (p.24), andzeranol (p.27).
101Ibid. 386, and1983 OIEScientific Report, p.339 etseq.
102J.Liehr, "Potential genotoxicity ofHormones", 23December 1996.
103Ibid.WT/DS48/R/CAN
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"...the1987 JECFA report must nowberegarded astooold.Themain problem withthis
report isthatitrelates anynegative effects ofhormonal drugs totheirhormonal effects, i.e.
ifacompound occurs inamounts notgiving clear"hormonal" responses itisregarded assafe.
Theanabolic steroid trenbolone hasbothanabolic andoestrogenic effects anditisnotclear
which effects areconsidered. Itisfrequently usedincombination withoestradiol andalso
withzeranol, which areestrogenic. Furthermore, testosterone andtrenbolone seem alsoto
affect theglucocorticoid receptor andtestosterone increases growth hormone andgrowth factor
concentrations andbothaffect steroid biosynthesis. Many other hormonal effects ofthefive
compounds dealt withareknown. When studying hormonal effects onlygross effects are
considered, butnowadays itisobvious thateffects mayoccur atthecellular level atlow
concentrations ofhormones andwithout being observable bytherelatively coarse methods
usedintoxicology invivostudies. Such effects maybeobservable inhuman subjects first
aftermany years orevenlonger time. Another problem isthattheJECFA report doesnot
dealwithordiscusses verylittlethecarcinogenicity ofmetabolites ofhormones, particularly
those ofoestrogens. Atthetimewhen the1987 JECFA Report waswritten verylittlewas
known about thegenotoxic effects particularly ofestrogen metabolites. Since thereport was
written ithasalsobeenmore andmore obvious thathormones havenongenomic effects not
related totheirhormonal effect viathereceptors andthatsteroid hormone metabolites may
beasimportant orevenmore important withregard tovarious effects onbiochemical or
genotoxic events thantheparent compound.
"Allthesehormones havebeenshown tocause cancer invarious experimental systems ifgiven
inhighamounts butitisobvious thattheeffect isnotalways duetotheirhormonal activity.
Foroestrogens andtrenbolone ithasbeenshown thatalsoother mechanisms occur andthe
mechanisms bywhich theother hormones cause cancer isfarfrom clear.
(...)
"Anabolic steroids inmeathasbeenshown toresult inpositive doping tests. Acompound
giving positive doping testscannot beadministered formeat production because these may
result inlifetime problems foranysportsman orsportswomen whoiscaught withapositive
doping testwithout having usedanydoping agents.
"The 1987 JECFA report isdefinitely toooldanddoesnottakeintoaccount recent scientific
evidence changing ourviewonthecarcinogenicity ofoestrogens anddoesnottakeintoaccount
non-hormonal andother negative effects oftheadministration ofsteroids toanimals intended
forhuman consumption".104
4.163 TheEuropean Communities alsopresented theargument ofDr.Cavalieri that:
"...thepresently available knowledge about tumour induction inhormone-responsive tissues
suggests aspecific pathway ofoestrogen metabolism, namely 4-hydroxylation followed by
oxidation toE-3,4-Qandreaction DNA. ThisDNA damage isresponsible forgenerating the
critical mutations thatcanleadtotumour formation, iftheappropriate mechanisms ofpromotion
occur. Therefore, oestrogens, inparticular oestradiol, havegenotoxic effects andnothreshold
dosecanbeestablished. Inaddition, theeffects oftheother natural andsynthetic hormones
usedformeatproduction onthemetabolism ofoestrogens arenotknown. Thus, Acceptable
Daily Intakes andMaximum Acceptable Levels cannot beestablished forresidues ofthese
hormones inmeatforhuman consumption.
104H.Adlercreutz, "Evaluation oftheThirty-Second Report oftheJointFAO/WHO Expert Committee onFood Additives,
andDiscussion ofDr.J.Liehr 'sReport onthisTopic", 7January 1997.WT/DS48/R/CAN
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"The 1988and1990 FAO/Codex Alimentarius expert group reports recommended ADIs and
MRLs forthese hormones based ontheirhormonal effects. Genotoxic effects wereunknown
atthattimeand,thus,werenotconsidered. Inlightofthenewknowledge about thegenotoxic
effects ofoestrogens, theentire subject ofthese residues inmeatforhuman consumption must
bereassessed."105
4.164 Furthermore, theEuropean Communities argued thatDr.Metzler reported thattheavailable
datashow that:
"17-oestradiol, 17-trenbolone andzeranol canbemetabolically activated toproducts capable
ofcovalent DNA binding. ThelevelofDNA binding islowascompared totypical chemical
carcinogens, butmayhavesignificant toxicological implications, asdiscussed below.
"17-oestradiol andsome oftheirmetabolites havethepotential tocause aneuploid andare
therefore chromosomal mutagens. For17-trenbolone, thereports about aneuploidogenic
potential arecontroversial. Forzeranol anditsmetabolites, aneuploidogenic potential hasnot
beenstudied adequately.
"The metabolism of17-trenbolone andzeranol inhumans andthegenotoxicity ofthe
metabolites havenotbeenfullyelucidated.
"The mechanisms ofhormonal carcinogenesis arenotyetfullyunderstood. Thehormonal
andgenotoxic effects ofanagent maywellactinconcert. Therefore, itisconceivable that
anhormonallyactivecompoundisretainedintargetcellsbythehormonereceptorandstimulated
celldivision, which inturnmakes thecellmore vulnerable fortheinduction ofgenemutations
andaneuploid. Xenobiotic hormones havelonger half-life andmayaccumulate tohigher levels
afterrepeated exposure.
"Thestandard systems usedintoxicology forassaying genotoxicity maynotbesuitable todetect
therather subtle genotoxic effects ofcarcinogenic hormones. Asthehormones under
considerationand/orsomeoftheirmetabolitesexhibitbothDNA-damagingandaneuploidogenic
potential, itisnotpermissible toestablish values forNo-Adverse-Effect-Levels andfor
Acceptable Daily Intake. Theconclusions andrecommendations ofthe1988 and1990
FAO/Codex Alimentarius Reports aresolely based onthehormonal activities oftheagents
under consideration. Astheevidence forgenotoxic effects ofthese agents hasincreased
considerably overthepastyears, anupdate isrequired which takes these recent findings into
account."106
4.165 TheEuropean Communities alsoreferred tothereport submitted byDr.Epstein inwhich he
argued that:
"...thereissubstantial evidence challenging thevalidity ofclassifying carcinogens asepigenetic,
forwhich thresholds orAcceptable Daily Intake (ADI) levels areclaimed, orgenotoxic. Apart
fromthis,hormonal anabolics aremutagenic inmammalian testsystems andarethusgenotoxic.
There isalsosubstantial scientific evidence challenging theexistence ofthresholds forany
carcinogen. Thisevidence isevenmore persuasive forexposures involving infants andyoung
children, inview oftheirenhanced sensitivity tocarcinogens andforexposures involving
105E.Cavalieri, "Genotoxicity andPotential Carcinogenicity ofHormones Administered toAnimals forPromotion of
Growth inMeat Production", 7February 1997.
106M.Metzler, "Genotoxic Potential oftheNatural SexHormones 17-oestradiol andTestosterone, andoftheSynthetic
Compounds 17-trenbolone andZeranol", 6February 1997.WT/DS48/R/CAN
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unpredictable synergistic interactions. There isnoscientific basis forclaims thatADIlevels
canbesetfornatural andsynthetic anabolic carcinogens, orforclaims thatADIlevels can
bebased on"no-hormonal-effect levels" ofsynthetic anabolic carcinogens (FAO/WHO, 1990).
"Theseconclusionsonthehormonaleffectsofanabolicsareconsistentwith,andanamplification
of,those detailed inanearlier review ofendocrine factors inhuman carcinogenesis. Inalmost
allcases twopostulated mechanisms: "alteration ofthesusceptibility oftissues totheinitiation
ofcancer" and"promotion ofthedevelopment ofcancer from initiated cells", could notbe
separated. Thecarcinogenic effects ofDESinrelation tobreast cancer were considered to
be"more inkeeping withaneffect oninitiation rather thanonpromotion". Itmayfurther
benoted thatnomechanism ofaction, whether promotion, initiation orother, could be
determined forthecarcinogenic effects ofoestrogens onsalivary, ovarian, renal andthyroid
cancers, andmalignant melonoma inhumans. Amostrecent report hasfurther summarized
evidence thatparent oestrogens andtheircatecholamine metabolites induce several types of
DNA damage, adduct formation, andgenemutations. Additionally, theauthor concluded,
onthebasis ofexperimental evidence, that"hormonal activity ofoestrogens wasconsidered
tobenecessary butnotsufficient fortumour induction tooccur".
"Thereisnoscientificbasisformakingdistinctionsbetweengenotoxicandepigeneticcarcinogens
onthebasisofavailable bioassay data. Thus, thereisnobasisforattempts toderive threshold
levels forhormonal anabolics, orother carcinogens, from suchdata. ...
"Itshould further beemphasized thatextrapolation from highdosebioassay dataislikely to
underestimate, rather thanoverestimate, thecarcinogenic effects oflowdosechronic human
exposure. Arecent publication endorsed thisconclusion withparticular reference tometabolic
considerations. "Limited evidence would indicate thatproportionately lessactive metabolite
isformed athigh concentrations where Phase 2enzymes predominate, while atlower
concentrations pathways leading toactive metabolites arefavoured. Theoverall effect would
leadtoanunderestimate ofriskfromhighdoseanimal experiments when extrapolating tolow
level, chronic human exposure."
"Apart from theinvalidity ofdistinctions between genotoxic andepigenetic carcinogens, it
isgenerally accepted thatthreshold levels cannot bedetermined forgenotoxic carcinogens.
While hormonal anabolics areinactive inbacterial genetests,andhence dismissed asepigenetic,
theyarenevertheless clastogenic inmammalian evidence ofgenotoxicity isclearly morerelevant
tohuman cancer thanaredatabased onbacterial genetests.
"There areother cogent reasons forrejecting thethreshold hypothesis. These include:
- Theenhanced sensitivity ofneonatal rodents tothecarcinogenic effects ofanabolic
hormones, supported bysubstantial evidence ontheincreased susceptibility ofinfant
rodents andhumans toawiderange ofcarcinogens, including natural anabolics and
diethylstilbestrol. (IARC, 1989, NRDC, 1989)
- Synergistic interactions between different anabolics administered incombination.
Illustrative, arethesynergistic effects ofoestrogen andprogesterone intheinduction
ofmammary tumours inmice. (IARC, 1987)
- Thepossibility ofadditive and/or synergistic interactions between natural andsynthetic
anabolic carcinogens andendogenous hormones, particularly ininfants.WT/DS48/R/CAN
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- Synergistic interactions, notasyetinvestigated, between anabolic carcinogens and
carcinogenic and/or xenoestrogenic contaminants inmeatproducts, suchaschlorinated
hydrocarbon pesticides.
- Theabsence ofroutine monitoring andresidue analysis forparent anabolics following
theirlegal administration, andofsensitive andpractical analytic techniques further
preclude attempts toestimate threshold orAcceptable Daily Intake levels forhormonal
anabolics. Stillfurther complicating problems ofresidue analysis istheimpracticality
ofassaying forbiologically active oestrogen metabolites."107
4.166 TheEuropean Communities alsopresented thearguments ofDr.Pinter that:
"...thereisevidence thatendogenous andexogenous hormones represent potential carcinogenic
risktohumans. Theriskisassociated withthelevelofhormones, thetimeofexerting the
hormonal effect andthegeneral status ofthehormone-responsive organs. Exogenously
administered hormones havebeenproved tobecarcinogenic toexperimental animals andthere
isalsoevidence forhormones tobecasually associated withhuman tumours. Incontrast to
many animal carcinogens, inthecaseofhormones, onehastobearinmind thatwedealwith
"human" carcinogens. Therefore, anyconsideration should bedealtwithmore seriously than
with"animal" carcinogens. Although thelevelofendogenous hormones varies greatly during
thelifetime, there isnoevidence thatlowlevel ofadditional hormones donotrepresent
additional risk.
"Oestrogens and/or theirmetabolites canreact withDNA causing DNA damages, canalter
proteins including tubulin, resulting inaneuploid. There isalsoevidence thatthiseffect is
differentfromthehormonalone,thereforerelyingonno-hormonaleffectmightbeinappropriate.
Administration ofoestrogens andprogestins inhumans isproved tobetumorigenic. Incase
ofhormone mixtures andtheirresidues, itispossible thatsimilar risksexists. Although the
levelofadministered oringested mixtures maybedifferent, thetumorigenic hazard should
notbeexcluded.
"Alleffort should bemade toavoid additional hormonal effect unless itisabsolutely necessary
(mediation, etc.). Theriskassociated withconsumption ofhormone-containing meatproducts
canberegarded asunnecessary riskwhich canbeavoided."108
4.167 Thelatest scientific evidence thusindicated thatoestrogens wereimplicated intheinduction
ofhuman cancers, andthere wasincreasing evidence ofasimilar roleforprogesterone and
testosterone.109Inthecaseofprogesterone andtestosterone, itwasnotclearwhether theircarcinogenic
effects weremediated bytheiraction onspecific receptors intarget tissues orduetomutagenic DNA
107S.S.Epstein, "Report totheEConCancer Risks from Hormonal Meat Products", 5February 1997.
108A.Pinter, "Some Aspects ofHormonal Carcinogenesis", 5February 1997.
109TheEuropean Communities citedthefollowing articles: J.G.Liehr (1990), "Genotoxic effects ofoestrogens, Mutation
Research," pp.269-276; D.RoyandJ.G.Liehr (1992), "Target organ-specific inactivation ofdrugmetabolizing enzymes
inkidney ofhamsters treated withoestradiol", Molecular andCellular Biochemistry 110,pp.31-39; B.T.Zhu, D.Roy
andJ.G.Liehr (1993), "The carcinogenic activity ofethinyl oestrogens isdetermined byboththeirhormonal characteristics
andtheir conversion tocatechol metabolites," 132Endocrinology, pp.577-583; M.Y.Wang andJ.G.Liehr (1994),
"Identification offattyacidhydroperoxide cofactors inthecytochrome P450-mediated oxidation ofoestrogens toquinone
metabolites," 269Journal ofBiological Chemistry, pp.284-291.WT/DS48/R/CAN
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damage.110Inthecaseofoestradiol, thelatest experiments hadshown thatitshormonal potency was
notlinked toitscarcinogenic activity.111Investigations ofthemetabolic pathways ofoestradiol had
revealed thatfreeradicals werecontinuously produced, andDNA damage bythese freeradicals, as
wellasDNA adduct formation, hadbeendemonstrated inarange oftissues. Asdamage toDNA and
DNA adduct formation wereknown tobeassociated withtumour formation, theseexperiments provided
strong evidence thatoestradiol wasagenotoxic carcinogen.112
4.168 TheEuropeanCommunitiessubmittedthattheADIandMRL recommendedbythe1988JECFA
Report were equally outofdate, since according tothesixscientific opinions presented above such
levelsweredifficulttodeterminegiventhepresentinsufficientknowledge.The1987IARCMonographs
alsoneeded tobeupdated onthehormonal -doseeffect level, asexplained bythesixexperts advising
theEuropean Communities withregard totheJECFA Report. TheEuropean Communities contended
thatpartofthescientific community; whose numbers wereincreasing steadily inthelightofprogress
made byscience, thebetter understanding ofthemode ofaction ofhormones andthedevelopment
ofbetter analytical methods, placed more attention onthecarcinogenic risksarising fromthepossible
genotoxic action ofthesehormones, irrespective ofthedoseinwhich theywereadministered toanimals
forgrowth promotion. Intheabsence ofclearevidence tothecontrary, theEuropean Communities
considered thatitwasentitled tofollow acautious approach andsidewiththisbodyofscientists. This
choice wasincompliance withtheproper definition oftheconcepts of"risk" and"risk assessment",
contained inArticles 5.1to5.6andinparagraph 4ofAnnex A,oftheSPSAgreement.
4.169 TheEuropean Communities referred thereports ofDr.Pérez-Comas inrelation todetection,
control andadministration ofhormones. Dr.Pérez-Comas argued that:
"anomalous sexual development inPuerto Ricoisamajor andserious public health problem.
(...)Wehavebeendetecting anincrease ofsuchcases since early in1969 uptothepresent.
Uptothisdateover1,500 patients havebeendocumented.
"From ourpatients, wehavededucted thatenvironmental contaminants areastrong factor
inetiology ofthecondition thataffects children ofbothsexes, different races andnationalities
residing inPR,andallagesintheform ofAnomalous Sexual Development. (...)Wehave
documented clinical evidence ofincreased serum totaloestrogens inasignificant number of
patients, withover60percentofthefemales withovarian cysts, variable levels ofFSH, LG
&Prolactin, thatrecede ordiminish inasignificant number ofpatients afterameatandpoultry
depletion diet.
"Wehavebeeninformed thatanomalous sexual development cases areincreasing inChile,
Bolivia andColombia. Astoourknowledge nodefinite cause havebeenfound, butpoultry
andmeat contamination isbeing considered, forinLatinamerica multiple useofgrowth
promoting hormones havebeendocumented. Weconsider thatinPRtheAnomalous Sexual
Development inchildren iscomplex withdifferent etiological factors suchaszeranol, other
110J.G.Liehr (1995), "Induction ofaDNA adduct detectable by32P-postlabeling inthedorsolateral prostate ofNBL/Cr
ratstreated withoestradiol-17 andtestosterone," 16Carcinogenesis, pp.951-954.
111B.T.Zhu, D.RoyandJ.G.Liehr (1993), "The carcinogenic activity ofethinyl oestrogens isdetermined byboth
their hormonal characteristics andtheir conversion tocatechol metabolites", 132Endocrinology, pp.577-583 (1993).
112J.G.Liehr (1994), "Mechanisms ofmetabolic activation andinactivation ofcatecholestrogens: abasisofgenotoxicity,"
6Polycyclic Aromatic Compounds, pp.229-239.WT/DS48/R/CAN
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unknown oestrogenic substances, andpesticides. Serious emphasis mustbedoneonthecontrol
ofthese substances anditsavoidance inanimal husbandry. (...)"113
4.170 With regard tothenature andmode ofaction ofhormones, Canada stressed thatacomplete
review oftheJECFA andIARC materials cited bytheEuropean Communities revealed thatthe
carcinogenic effects ofthethree natural hormones occur onlyatdoses thatcaused obvious hormonal
effects. JECFA hadconcluded that,astheamount ofthese hormones ingested inmeatfrom treated
animals would beincapable ofexerting ahormonal effect, theywould beincapable ofexerting atoxic
effect inhumans (seeparagraph 2.22). Similarly, JECFA 'srecommended MRLs forzeranol and
trenbolone werebased ontheirno-hormonal-effect level. Humans consumed arange ofcarcinogens
intheirdietsasillustrated bythefactthat27natural pesticides thatwerecarcinogenic inrodents were
present atlevels above 10ppminawidevariety offoods, including anise, apple, basil, brussels sprouts,
cabbage, carrot, cauliflower, celery, cherries, clovers, coffee (brewed), comfrey herbtea,dill,eggplant,
mustard (brown), nutmeg, orange juice, parsley, parsnip, pear,pepper (black), plum, potato, rosemary,
sage, sesame seeds (heated), tarragon andthyme. Inaddition these 27natural pesticides werepresent
inalarge number ofother foods.114InCanada 'sview, thekeyfactor wasthedose: atthelowlevels
ingested, these substances didnotappear toposeahazard tohuman health.
4.171 TheEuropean Communities didnotdenythatthere wasprobably stillanumber ofscientists
whobelieved that"thecarcinogenic effect ofthese hormones isrelated tothehormonal activity of
thesecompounds, i.e.anincrease intumour incidence intissues ofanimals withhighlevels ofspecific
hormone receptors, which would notoccur atnormal physiological levels". However, thisviewwas
notheldbyanother partofthescientific community; apartwhose numbers wereincreasing steadily
inthelightofprogress made byscience, thebetter understanding ofthemode ofaction ofhormones
andthedevelopment ofbetter analytical methods. Thiswasthescientific opinion ofDr.Liehr and
oftheother scientists cited therein. Intheabsence ofclear evidence tothecontrary, the
European Communities considered thatitwasentitled tofollow acautious approach andsidewiththe
bodyofscientistswhoplacedmoreattentiononthecarcinogenicrisksarisingfromthepossiblegenotoxic
action ofthesehormones, irrespective ofthedoseinwhich theywereadministered toanimals forgrowth
promotion. Thischoice wasincompliance withtheproper definition oftheconcepts of"risk" and
"risk assessment", contained inArticles 5.1to5.6andinAnnex A.4oftheSPSAgreement.
(ii) Metabolites
4.172 TheEuropean Communities argued thatother risksarose fromthehormones atissuebecause
oftheirmetabolites. When drugs wereintroduced intothebody, theirpharmacological andtoxiceffects
weredirectly correlated totheirconcentration intissues andfluids. Theconcentration ofadrugwas
afunction ofitsresorption, excretion andmetabolism. Drugs weremetabolized (broken down) and
theirmetabolites might alsohavepharmacological effects, which might differ from theeffect ofthe
parent drug. Metabolites might havedifferent sideortoxic effects. Anabolic steroids hadalarge
variety ofmetabolites, some ofwhich wereonlyrecently identified. Thepharmacological andtoxic
behaviour ofmany ofthese metabolites werestillunknown. Inaddition, thesame parent substances
might produce different metabolites indifferent species, making theextrapolation from studies on
laboratory animals tohumans unreliable.
113A.Pérez-Comas andC.A. Saénz, "Anomalous Sexual Development inPuerto Rico: 28years ofExperience",
28February 1997.
114B.Ames,"HumanCancer:ArePesticidesResponsible?"(1992)45WesternSocietyofWeedScience15,p.17.Canada
submitted thatinaddition, thecooking offoodwasalsoamajor dietary source ofsubstances thatwerecarcinogenic inrodents.
"Cookingproducesabout2000mgperpersonperdayofmostlyuntestedburntmaterialthatcontainsmanyrodentcarcinogens-
forexample, polycyclic hydrocarbons, heterocyclic amines, furfural, nitrosamines -aswellasaplethora ofmutagens" Ibid.,
p.18WT/DS48/R/CAN
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4.173 TheEuropean Communities asserted thattherewerescientists whoargued thatknowledge about
thetoxicity ofthemetabolites ofthese hormones wasasyetverylimited. Moreover, metabolites of
suchsubstances which, eveninlowconcentrations, might havehighly toxic effects were generated
inthehuman body.115These scientists argued that"theuseofhormones ingrowth promotion ofanimals
should notbeallowed, asitcannot beexcluded thatunchanged agents, theirmetabolites and,above
all,unknown highly effective andtoxic metabolites aredistributed withthemeatwhich ispurchased
byconsumers".116Moreover, insome oftheexperimental studies onwhich the1988 JECFA Report
wasbased, noextensive research andriskassessment ofthepotential risksarising fromthemetabolites
ofthehormones under consideration hadbeencarried out.117Noting thatdespite alltheuncertainties,
JECFA haddecided toestablish atemporary ADIfortrenbolone acetate while requesting additional
information tobesubmitted toitby1990, theEuropean Communities argued thatinlightofthe
arguments advanced bysome scientists, itwasquestionable whether thedecision oftheJECFA could
beregarded asareasonable one.
4.174 TheEuropean Communities added that,asDr.Liehr118andtheother scientists advising the
European Communities, aswellasother scientists119hadshown, themetabolic pathways ofoestradiol
hadrevealed thatfreeradicals werecontinuously produced, andDNA damage bythese freeradicals,
aswellasDNA adduct formation, hadbeendemonstrated inarange oftissues. These experiments
withthemetabolites ofoestradiol provided strong evidence thatoestradiol (andpossibly theothernatural
hormones) wasagenotoxic carcinogen. Therefore, the1988 JECFA Report wasoutofdatealsoin
thisrespect andneeded tobeupdated inthelightofthemost recent scientific evidence.
4.175 Canada claimed thattheECarguments withrespect tometabolites didnotidentify anyrisk
posed bythesixhormones atissuewhen usedforgrowth promoting purposes inanimals. TheEuropean
Communities focused ontheconclusions ofonepaper presented inthe1995ECScientific Conference
thatexamined theillegal useofanabolic steroids inathletes andnottheuseofthesixhormones at
issueforgrowth promotion incattle. Moreover, withregard totheabsence ofsatisfactory toxicological
dataontrenbolone metabolites intheJECFA Report, theEuropean Communities failed tonotethat
theadditional research onthese metabolites hadbeenprovided toJECFA before ithadmade itsfinal
recommendation.120
115W.Schänzer, "The Illegal useofAnabolic Agents inSport", 1995 ECScientific Conference Proceedings, p.352.
116Ibid.,p.353
117Asanexample, theEuropean Communities noted that,asregards trenbolone acetate (TBA), theJECFA hadstated
that"Intheabsence ofsatisfactory toxicological datatheCommittee wasunable toestablish aseparate no-effect level for
thea-TBOH metabolite. Italsonoted thatthismetabolite wasnotproduced insignificant amount intherat,which made
itinadvisable toextrapolate from datagenerated from ß-epimer, experiments inthatspecies".
118J.G.Liehr, (1990), "Genotoxic effects ofoestrogens, 238Mutation Research" 269-276; J.G.Liehr, (1994),
"Mechanisms ofMetabolic Activation andInactivation ofCatecholestrogens: Abasis ofgenotoxicity, 6Polycyclic Aromatic
Compounds" pp.229-239.
119B.T.Zhuetal.(1993), "The carcinogenic activity ofethinyl oestrogens isdetermined byboth their hormonal
characteristics andtheirconversion tocatechol metabolites," 132Endocrinology, pp.577-583; M.L.Winter etal.,"Possible
mechanism ofinduction ofbenign prostatic hyperplasia byoestradiol anddihydrotestosterone indogs" (1996), 136Toxicol.
Appl. Pharmacol, pp.211-219.
120"Evaluation ofcertain veterinary drugresidues infood: Thirty-fourth Report oftheJointFAO/WHO Expert Committee
onFood Additives," Technical Report Series 788(Geneva: WHO, 1989), pp.40-42.WT/DS48/R/CAN
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(iii) Combinations ofhormones andmultiple exposure
4.176 Referring toscientists 'reports atthe1995ECScientific Conference ofevidence oftheillegal
useofgrowth-promoting substances inmany European countries andelsewhere121,theEuropean
Communities submitted thattheillegal useofmixtures ofveterinary drugs andgrowth promoters might
result inunpredictable residue levels inedible foods, which might constitute ariskfortheconsumer.
Thismight beduetovariations inphysiological andpathological parameters, altering drugdisposition
andelimination. Biotransformation patterns ofsynthetic drugs andhormones might differ markedly
depending ontheanimal species andgender. Interactions might occur between compounds ashad
beenreported forsulphadimidine andoestrogenic andandrogenic hormones administered todwarf goats.
Thismight require longer withdrawal times inorder toarrive atsaferesidue levels. Forthose reasons,
the1995ECScientificConferencehadconcludedthat"theuseofcombinations(orcocktails)ofhormones
poses serious risks forthehealth ofconsumers because theuseofmixtures, which usually contain
illegal substances, ismade intheform ofinjections, rather thanimplants, andthisisanimpediment
totheirdetectionatslaughter.Thispotentiallyallowsthesaleofmeatcontainingveryhighconcentrations
ofhormones".122
4.177 TheJECFA Report hadpointed clearly totheneedtoexamine theeffects ofcombination:
"The Committee noted thatseveral ofthehormonally active substances ontheagenda were
usedincombination onewithanother, andrecommended that,where substances having similar
physiological activities were combined, evidence thattheirhormonal effects were additive,
rather thansynergistic, should beprovided. TheCommittee agreed thatdataontheresidues
ofeachofthesubstances thatareusedincombination should beavailable forevaluation, whether
ornottheirphysiological activities were similar" (page 7).
However, despite thiswarning, theJECFA Report hadnotexamined theadditive orsynergistic effects
ofanyofthese hormones, despite thefactthatitwasfullyaware thatcombinations ofthesesubstances
werecommercially available. Scientists agreed thattheconcept ofADIwasnotapplicable toassess
theriskfrom exposure tomixtures (orcocktails) ofcompounds. IntheECview, thepotentially
disastrous effects ofcocktails ofhormones wasnowclearly highonthescientific agenda, ashadbeen
recently reported foroestrogenic environmental compounds:
"Therelatively lowpotencies ofeachofthese compounds havesuggested thatthese chemicals
alone areunlikely toproduce adverse health effects inhumans. However, these compounds
occur asmixtures intheenvironment, andtheircombined action hasnotbeenwellstudied."123
4.178 Thereport referred toscientific research which established thatcombinations (cocktails) of
twoweak environmental oestrogens (anatural environmental hormone) were1000times more potent
thananycompound alone. Andthereport concluded asfollows:
"Thepossibility forsynergistic action ofapparently inactive chemicals functioning ashormones
mayrepresent apreviously uncharacterized levelofreceptor-mediated generegulation .The
121Steering Committee, "Report andConclusions", 1995 ECScientific Conference Proceedings, p.9.
122Ibid.,p.9,andH.A.Kuiper,"RiskAssessmentStrategiesforXenobiotics",1995ECScientificConferenceProceedings,
p.376.
123"Synergistic Activation ofOestrogen Receptor withCombinations ofEnvironmental chemicals," 7June1996, Science,
Vol.272, pp.1489-1492.WT/DS48/R/CAN
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interaction ofmultiple chemicals withtheoestrogen receptor suggests acomplex interplay
between environmental signals andbiological systems"124(emphasis added).
TheEuropean Communities concluded thatthere wasconsiderable potential hazard arising from the
useofcombinations, containing authorized orunauthorized hormones, andtheexisting international
rules didnotdealadequately withthispotential hazard.
4.179 Canada argued thattheECdiscussion ofcombinations and"cocktails" blured thedistinctions
between combinations ofhormones present inlegal, approved veterinary products, andmixtures
containing illegal drugs suchasthose soldontheblack market intheEuropean Communities. The
formulationsinapprovedhormonalimplantscombinedhormonestobalancethehormonaleffects,achieve
optimal growth promotion, andregulate therelease rateofthehormones intheimplant. InCanada,
aveterinary product wasapproved afteracomprehensive review ofthedrugasformulated .Thus,
Canada 'sreview ofapproved hormonal implants containing acombination ofhormones examined the
safety ofthese substances incombination .Inaddition, thehormonal implants approved inCanada
didnotcontain combinations ofsubstances thathadthesame hormonal effect: trenbolone wasnot
combined withtestosterone, zeranol wasnotcombined withoestradiol-17 ,andMGA wasnotcombined
withprogesterone.
4.180 Incontrast tothecombinations ofhormones found inlegal, approved veterinary products,
"cocktails" were mixtures containing illegal substances andCanada agreed thattheuseofillegal
substances, whether usedsingly orin"cocktails", wasdangerous. These substances werenotatissue
here, andtheEuropean Communities hadnotpresented anyevidence toshow thatpreventing theuse
ofthese illegal substances would alsorequire thecomplete prohibition ontheuseofthesixhormones
atissue.
4.181 Canada referred totheanswers ofthescientific experts, whonoted thatlegally marketed
combinationsofgrowthpromotinghormoneshavebeenexamined,approvedandregisteredbycompetent
national authorities. Moreover, asDr.Arnold noted inhiswritten answers tothePanel'squestions:
"...thepharmacodynamic andtoxic effects ofpractically allcombinations ofoestrogens,
progestins andandrogens onecanthink about havebeenstudied inwhole animals, organs,
tissue andcellcultures, andother invitrosystems under agreatvariety ofconditions andthese
effects areknown from literature."125
Canada recalled thatDr.Arnold stated thatlegally permitted combinations wereusednotonlyforgrowth
promotion purposes, butalsoforthepurposes permitted bytheEuropean Communities, suchasthe
synchronization ofoestrus.126
4.182 Canada stated thatontheissueofsynergistic effects, Dr.Arnold noted thattherewereavariety
ofsynergistic andantagonistic interactions among thehormones, butthatatthelevels ofresidues present
intreated animals, itwasnotapparent whatkindofhazards could arisefrommaximal changes ofless
than0.1percentininternal, human hormone pools duetotheconsumption ofmeatfromahormone-
124Ibid.
125Dr.Arnold, answer toPanel question 15,para. 6.159.
126Ibid., para. 6.159.WT/DS48/R/CAN
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treated animal.127Inaddition, Canada informed thePanel thatthesynergistic effects ofenvironmental
oestrogens citedbytheEuropean Communities asreported byMcLachlan etal.128hadnotbeenfound
byfourother laboratories thattriedtoreplicate theexperiments.
4.183 Noting thatatleastninecombinations ofhormones forgrowth promotion werefreely available
forsaleinCanada, theEuropean Communities contended thatrisksmaypotentially arisefrom the
multiple exposure ofhumans tohormones andother chemical substances which weresimilar tothose
resulting fromtheillegal useofcombinations (orcocktails) ofhormones. Allfoodstuffs, whether of
animal orplantorigin, werelikely tocontain traceamounts ofseveral substances derived fromvarious
sources, afactcurrently notaddressed inanyriskassessment strategy forfood. Because theADIand
MRL assessed thesafety ofasingle compound andnottheexposure tomixtures ofcompounds, a
sufficient protection ofhumans wasonlyguaranteed iftheMRL wasnotexceeded. Thus, there was
asubstance-related risktoconsumers iftheacuteingestion ofaresidue amount exceeded theestablished
MRL andpossibly theADI. TheCodex itself hadnoted that"Uncertainty inthesafety evaluation
process isprimarily addressed through theuseofsafety factors. Their respective values arearbitrary
andhavenomeasured biological significance, however, theirappropriateness issomewhat borne out
byexperience".129The"safety factor", therefore, might notprovide thenecessary protection, especially
inthecaseofpotentially carcinogenic substances whose mode ofaction wasnotclear, astheexample
ofthehormone DES130hadshown. The"safety factor" wasinreality nomore thanauseful tooland
applied tothose scientific reports which depended onextrapolations fromimperfect dataonlaboratory
animals tosetADIs andMRLs forhuman beings. Although these concepts hadserved wellinthe
pastandwould continue todosointhefuture, aMember wasentitled todeviate fromthese concepts
asusedbyCodex inestablishing recommendations. Codex hadproven tobeuseful insetting guidelines
andrecommendations forfoodadditives precisely because ithadleftitsmembers freetodecide whether
theywould accept itsrecommendations. TheSPSAgreement wascastlargely onthesamebasis, because
itallowed itsMembers todepart frominternational standards, guidelines orrecommendations under
theconditions laiddown therein (e.g.Article 3:3).
4.184 TheEuropean Communities further contended thatthequestion alsoarose onhowtoprotect
consumers fromapotential adverse effect resulting fromlong-term treatment withgrowth- promoting
substances. Such adverse effect wasthepossibility thatthebiotransformation ofother compounds
maybealtered, ashadbeenshown inthecaseofsteroids. Thismight result inaltered residue kinetics
forthose compounds.131TheEuropean Communities claimed thattheideathatthere maybearisk
associated with thelong-term exposure toamixture ofsubstances, resulting inapossible
127Ibid.. ,para. 6.159.
128ECfirstwritten submission.
129"RiskAssessmentProceduresusedbytheCodexAlimentariusCommissionanditsSubsidiaryAdvisoryBodies,"(1993),
Codex Alimentarius Commission, p.11.
130TheEuropean Communities explained thatDiethylstilboestrol (DES) wasasynthetic hormone which improved both
rateofgainandfeedefficiency inpoultry, cattle andsheep. DESwasperhaps themostwidely known ofoestrogenic growth
promoting agents. ItwasfirstusedintheUStherapeutically inpregnant women inthe1940'stoprevent abortion. TheUS
Government approved itsuseasafeedadditive forpoultry in1947, forcattle in1954 andlaterforsheep. In1971, its
carcinogenic effects inhumans andinlaboratory animals wasclearly established. Additional studies showed thatDES had
other effects ondaughters andsonsofmothers treated withit,themost common being vaginal adenosis andother gross
abnormalities ofthereproductive tract. Atthetime(1976) these studies were published, anestimated 25million cattle and
7million sheep were being treated withDES. Still,itscomplete withdrawal from theUSmarket wasachieved onlyin1978,
while inthemeantime theUSFDA wastrying todiscover andfixacceptable "noresidue" limits.
131"Assessment ofHealth Risk", Working Group II,1995 ECScientific Conference Proceedings, p.20.WT/DS48/R/CAN
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biotransformation ofother compounds, wasaprecursor totheso-called "precautionary" principle and
itwasattheheart ofthepolicy followed bytheEuropean Communities onsuchissues132.
4.185 Canada argued thatinitsdiscussion ofmultiple exposure, theEuropean Communities had
notidentified anyriskposed bythesixhormones atissue. Moreover, ifthere wereanyconcern over
lifetime exposure toavariety ofchemicals, itwould apply equally welltoother veterinary drugs.
Yetinitsapproval procedures fornewveterinary drugs, itwould appear thattheEuropean Communities
didnotrequire thetesting ofnewdrugs incombination withallexisting drugs toensure there was
no"...riskassociated withthelong-term exposure toamixture ofsubstances resulting inapossible
biotransformation ofothercompounds ....". Thiswasnotsurprising, sincethenumber ofcombinations
andpermutations ofveterinary drugs would render thetaskimpossible. YetitwasafactthatECfarm
animals were exposed toavariety ofveterinary products throughout theirlives.
(iv) Detection andControl
4.186 TheEuropean Communities argued thatdifficulties arose because theidentification ofanimals
ormeatfromanimals which hadbeentreated withthethree natural hormones wasdifficult duetothe
widevariation innatural levels ofthese hormones arising because offactors suchassex,age,diet,
physiological condition, etc.While residue analysis fornatural hormones intreated animals could
experimentally show differences between them anduntreated animals, itwascurrently notpossible
through routine teststoidentify treated animals onthebasis ofassays ofedible tissue samples, and
itwasalsodifficult using blood, urine orfaeces. Acountry allowing imports ofanimals andmeat
from animals treated withhormones would havetorelylargely onchecks andcontrols onuseof
hormones carried outbytheexporting country iftradewasnottobeimpeded, buttheimporting country
would alsohavetocarry outchecks andcontrols inorder toensure thatitsconsumers atemeatwhich
conformed totherequisite standards. Detection andsurveillance ofhormones wasbased onscreening
methods,principallyimmunoassays(radioorenzymeimmunoassays)becausetheywererapid,relatively
lowcostandcould beapplied simultaneously toalarge series ofsamples.133However, theEuropean
Communities claimed thatalltheavailable methods usedfordetection andcontrol hadtheirlimits and
drawbacks. Furthermore, although Codex hadestablished anadhocworking group onthematter,
there were stillnointernationally agreed rules forthemethods tobeused forresidue control
programmes.134TheEuropean Communities argued thatinlightofthepotential riskstohuman and
animal health resulting from theuncertainties inresidue control programmes andtheabsence of
internationally agreed rules, anyMember (including theEuropean Communities) wasentitled toadopt
aregulatory system toachieve thelevelofprotection foritspublic thatitconsidered tobeappropriate.135
4.187 TheEuropean Communities added thattheCodex Alimentarius Commission didnotestablish
MRLs forthethree natural hormones essentially because ofthedifficulty indetecting andmeasuring
theresidues, notbecause theirpresence athighconcentration levels would notposeriskstohuman
health (asdidtheresidues ofthesynthetic hormones forwhich MRLs wereestablished). However,
132Seealsothereply ofDr.Lucier toquestion 15,para. 6.161.
133M-LScippo andGMaghuin-Rogister, "Methods ofDetection andSurveillance ofNatural SexSteroid Hormones",
1995 ECScientific Conference Proceedings, p.541 etseq.
134TheEuropean Communities stressed thatin1991 theCodex Commission hadonlyestablished provisional methods
toserve asapotential source ofuse.SeeJoint FAO/WHO Food Standards Programme, Residues ofVeterinary Drugs in
Food, Vol.3,2ndEd.,1993.
135TheEuropean Communities noted that,forexample, Argentina prohibited theuseofthethree natural hormones (while
allowing theuseofthetwosynthetic ones), citing asanessential motive fortherestriction thelackofsuitable methods for
measuring hormone residue levels inmeat. 1983 OIEScientific Report, atp.411.WT/DS48/R/CAN
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Canada 's1996Planfortheexamination ofresidues inliveanimals andfreshmeatappeared toinclude
testing evenforthenatural hormones, although thedetection limitwassaidtobe"qualitative".
4.188 TheEuropean Communities claimed thatthehormones were verypowerful andgenotoxic
substances. Risks toconsumers 'health could notbeexcluded ifhormonally active growth promoters
wereabusively administered. Itwasunlikely thatauthorization ofthesesubstances asgrowth promoters
would endtheirextreme misuse potential. Itwasobvious thattheauthorization ofasubstance distinctly
restricted itscontrollability; thus, themisuse ofauthorized substances washardly controllable.
Therefore, inthecontext ofapreventive protection ofconsumers 'health itshould beself-evident to
takethemisuse potential ofasubstance intoconsideration. Ifhealth riskstoconsumers could notbe
excluded when asubstance wasmisused, single substances withanextreme misuse potential could
alsobebanned evenifthesubstances were nothazardous inthecaseofalegalapplication.136
4.189 TheEuropean Communities noted thatthereport oftheFood Inspection Directorate ofCanada
onmeatandeggproducts(Volume1,fiscalyear1995/96)providedthefollowinginformationasregarded
violations oftheMRLs setbyCanada: forzeranol :1violation outof276samples ofbeefbileand
livertested,fortrenbolone:1violationoutof33samplesofbeeflivertested,3violationsoutof155veal
liverand3vealmuscle tested; forMGA:2violations outof69samples ofmares tested. TheEuropean
Communities argued thathaditchosen toapply theMRLs recommended byCodex, itwould have
exposed itself topossible violations initsmarket ofproducts which would belegally marketed and
used. Forthatreason, itslevelofprotection could havenotbeenobserved. Alevelofprotection of
noresidues ofthese hormones inmeatdestined forhuman consumption, coupled withtheother strict
conditions imposed byEClaw,were considered bythecompetent ECauthorities tobetheonly
reasonably available measures tosafeguard human andanimal health intheEuropean Communities.
Ifviolations ofthislevelofprotection werediscovered fromtimetotime, thiscould result onlyfrom
illegal useofprohibited substances (ariskinherent inanylegal system) andnotfrom theuseof
authorized products.
4.190 Canada claimed thattheECdiscussion ofdetection andcontrol failed toidentify anyriskposed
bythesixhormones atissue when usedforgrowth promoting purposes inanimals. Detection ofthe
misuse ofsubstances wasnecessary whether products wereallowed ornot.Presumably, theEuropean
Communities sampled andtested meatproduced intheEuropean Communities andimported meatfor
excessive levels ofallpermitted drugs. Thedetection ofillegal substances (such asbeta-agonists) was
notimpaired bypermitting thesixhormones atissue forgrowth promotion.
(v) Administration anduseofhormones
4.191 TheEuropean Communities observed thatallscientists agreed thatifthehormones atissue
wereallowedtobeusedforanimalgrowth,theymustbeadministeredinaccordancewithgoodveterinary
practice. Thisrequirement wasapparently shared alsobyCanada, which often stated that"hormones
areusedandregulated asveterinary drugs inseveral countries, including Canada, theUS,Australia
andNew Zealand". However, theEuropean Communities argued thatiftheterms "regulated as
veterinary drugs" referred togrowth promoters, thenitwasnotbeing usedinasense which the
European Communities would recognize. This wasapparent from theconditions under which
"RALGRO", anhormone implant containing zeranol, waspermitted tobeusedinCanada. According
tothe1995 Compendium ofVeterinary Products usedinCanada, "RALGRO" implanting might be
repeated "asoften asgoodhusbandry practice allows through thegrowing andfinishing phases ofthe
animal 'slife". Indeed, itwould appear thatnoneofthehormones atissue hadtobeadministered by
aveterinarian when usedforgrowth promotion.
136See1995 ECScientific Conference Proceedings, pp.537-539.WT/DS48/R/CAN
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4.192 TheEuropean Communities shared theviewthatthesehormones should beusedinaccordance
withgoodveterinary practice when administered forgrowth promotion, sincewhen theECCommission
considered thealternative ofpermitting theuseofthethreenatural hormones onlyforgrowth promotion
in1984137,itthought necessary tospecify sixconditions ofadministration inorder tosafeguard public.
Oneofthese conditions wasadministration onlybyaveterinarian. TheJECFA Report required that
usepatterns bebased ondatasubmitted "onthepatterns ofuseofeachveterinary drug, including
information about whatarerecognized asgoodveterinary oranimal husbandry practices under different
localconditions" (page 11).The1995ECScientific Conference hadalsoconcluded that"compliance
with Good Agricultural and Good Veterinary Practice arenecessary" (page 5). The
European Communities pointed outthat,asthesehormones wereveterinary drugs, theyhadtobeused
inaccordance withgood veterinary practice, aslaiddown inthelegislation ofeachMember. This
wasprovided forbytheCodex Code ofPractice, which allowed Members todecide whether veterinary
products (likethehormones) should beusedonlyinaccordance withlabelinstructions approved by
theauthorities, oratleastunder prescription andinstruction ofaqualified veterinarian. Canada had
choosen thefirstapproach, failing toperform therequired number ofcontrols andtesting toensure
theirrespect. After having examined thesecond approach, theEuropean Communities haddecided
thatthecosts ofthevarious elements ofcontrol involved would beveryhightoeffectively ensure its
levelofprotection. Forthese andother reasons, explained inthisreport, theEuropean Communities
haddecided against theuseofthese hormones infoodproducing animals forgrowth promotion. As
regarded veterinary medicinal products (i.e.allveterinary therapeutic products), theEClegislation
conformed totherequirements oftheCodex Code ofPractice. IntheECview, zootechnical usemust
alsobeperformed byaveterinarian orunder hisdirect supervision, because itdidnotdiffer fromthe
administration point ofview from useofthese hormones fortherapeutic purposes. Indeed, the
zootechnical purposes mentioned intheEClegislation didnotdiffer inessence fromtherapeutic use;
ifsimilar treatments were performed onhuman beings theywould beperformed bydoctors alone.
Thatwasthereason whyintheEuropean Communities therapeutic orzootechnical usewaspermitted
onlyifperformed bytheveterinarian (orunder hisdirect supervision forsome types ofzootechnical
use), withalltreatments recorded andthetreated animals identified inorder torespect withdrawal
periods.
4.193 TheEuropeanCommunitiesobservedthattheCodexdefinitionslefttheresponsibilityofdefining
theactual conditions inpractice tonational authorities. Theeffect ofthiswasthatgood practice,
veterinary oragricultural, wascompliance withnational rules. However, nowhere didCodex suggest
thatcountries should accept eachother'sstandards automatically asbeing incompliance withgood
practice. AsfarastheEuropean Communities wasconcerned, Good Veterinary Practice intheuse
ofhormones wasthesetofconditions defined initslegislation. TheEuropean Communities didnot
accept thatpotentially dangerous veterinary drugs could begiven tofarmers touseinaccordance with
"Good Agricultural Practice", astheymight usepesticides orfertilisers. Good veterinary practice
wastheproper conduct ofaveterinarian, notasub-set offarming. Theterms ofreference ofJECFA
included theobligation todetermine acceptable andsaferesidues levels forveterinary drugs infood
"when thedrugs inquestion areadministered toanimals inaccordance withgoodveterinary andanimal
husbandrypractice".Forthehormonegrowthpromoters,the1988JECFAseemedtohavehadforgotten
about theveterinary aspect, eventhough these wereveterinary drugs withpowerful physiological and
toxicological properties. Thiscontrasted sharply withother JECFA reports onveterinary drugs with
comparable toxicological properties which provided intheirevaluation thattreatment ofanimals should
bemade inaccordance withgood practice intheuseofveterinary drugs.138
137COM(84)295.
138TheEuropean Communities noted thatthishadbeenthecase, forinstance, ofthedrugs carbadox andolaquindox (1991
JECFA report, 36thmeeting, pages 169and202, WHO Series 27(1991)).WT/DS48/R/CAN
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4.194 TheEuropean Communities argued thatalthough Codex hadrecommended anInternational
Code ofPractice forControl oftheUseofVeterinary Drugs in1993, itwasnotclear howfarand
howstrictly thisCodex Code ofPractice wasadhered tobycountries. Moreover, despite theobvious
needtoadminister hormones inaccordance withgoodveterinary practice, theJECFA Report considered
thatfiveofthese hormones werenotlikely toposeriskstohuman health ifused"inaccordance with
goodanimal husbandry practice", atermwhich ithadnotdefined. Theterm"Good Animal Husbandry
Practice" wasassumed tobeanalogous to"Good Agricultural Practice", butreferred specifically to
good practice inthecareandrearing ofanimals. Itwasalsousedinrelation to,forexample, feeding
andhousing offarmanimals.
4.195 IntheviewoftheEuropean Communities, thephrase "good animal husbandry practice" did
notmakesenseregardingpotentiallycarcinogenicsubstances.Thedifferencebetween"goodagricultural
practice" and"good veterinary practice" wassignificant. Good veterinary practice wastheproper
conduct ofaveterinarian, notasub-set offarming. "Good Practice intheUseofVeterinary Drugs"
wastheofficial recommended orauthorized usage including withdrawal periods, approved bynational
authorities, ofveterinary drugs under practical conditions. "Good Agricultural Practice intheUse
ofPesticides" included thenationally authorized safeusesofpesticides under actual conditions necessary
foreffective andreliable pestcontrol. Itencompassed arange oflevels ofpesticide applications up
tothehighest authorized use,applied inamanner which leftaresidue which wasthesmallest amount
practicable.
4.196 TheEuropeanCommunitiesarguedthatforthehormonegrowthpromoters,JECFAhadpromptly
forgotten about theveterinary aspect, even though these were veterinary drugs with powerful
physiologicalandtoxicologicalproperties,referringonlyto"goodanimalhusbandrypractice".However,
theCodex Commission hadstated withregards tozeranol that:
"The Committee noted thattheAcceptable Residue Level, established byJECFA hadbeen
based onthemaximum residue levels occurring afteruseofthesubstance inaccordance with
Good Practice intheUseofVeterinary Drugs andwaswellbelow thelevelwhich would be
ofanytoxicological significance".139
Equally, other JECFA reports onveterinary drugs provided thattreatment ofanimals should bemade
inaccordance withgoodpractice intheuseofveterinary drugs. Thiswasthecaseofdrugs likecarbadox
andolaquindox.140
4.197 TheEuropean Communities noted thattheCodex definition ofa"veterinary product" was
provided inparagraph 3oftheRecommended International Code ofPractice forControl oftheUse
ofVeterinary Drugs, which readasfollows:
"Veterinary products (including premixes formanufacture ofmedicated feedingstuffs) used
infoodproducing animals should beadministered (orincorporated intofeed) incompliance
withtherelevant product information approved bynational authorities and/or inaccordance
withaprescription and/or instruction issued byaqualified veterinarian".
Itfollowed thatamember ofCodex wasallowed torequire thataveterinary product, usedforimproving
animal production, might beusedonlyonprescription andunder thedirect supervision ofaqualified
veterinarian. Thiswasclearly notthesituation inCanada, where theseproducts wereusedbyfarmers
without prescription. TheEuropean Communities argued thatinCanada, thenumber ofanimals tested
139Alinorm 89/31A, Codex Commission, 18thsession of3-12 July1989, p.10, para. 78.
140"Toxicological evaluation ofcertain veterinary drugresidues infood," 1991 JECFA Report, 36thmeeting, WHO Food
Additives Series 27,pp.169 and202.WT/DS48/R/CAN
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wasverysmall andyetwithin thisextremely small number ofsamples violations oftolerance levels
hadbeenrecorded. Thequestion thencould bewhether thisinformation should betaken intoaccount
when performing ariskassessment. Inviewofthepotential formisuse andthepowerful incentives
forfarmers nottorespect theconditions ofuseprescribed inthelabels, itcould bemore appropriate
toprohibit theuseofthese substances forgrowth promotion. Useonprescription andunder thedirect
supervision ofaqualified veterinarian wasoneoftheconditions under which theECCommission had
considered theoption ofallowing theuseofthethreenatural hormones forgrowth promotion in1984,
whichhadbeenrejectedforthereasonsexplainedabove(paragraph4.18)bythecompetentEClegislative
bodies. TheEuropean Communities indicated thathighcosts probably explained theextremely low
percentage oftestsandcontrols performed inCanada, because theeconomic benefit derived fromthe
useofthese hormones forgrowth promotion would probably notsuffice toundertake anappropriate
levelofcontrol.
4.198 TheEuropean Communities argued thattherewereadditional riskstohuman andanimal health
arising from theadministration andpotential misuse ofhormones. Scientists hadargued that:
"Inthepresent concept ofestablishing MRLs based ongoodveterinary practice, thepossibilities
todetect amisuse ofauthorized substances aremainly reduced toadirect proof. (...)The
profitable misuse ofauthorized hormonally active growth promoters doesnothavetoleadto
aviolation oftheMRL, either, ifanMRL isestablished atall.Inthecaseofhormonally active
growth promoters, too,amisuse could behazardous toconsumers ifinstead oftheauthorized
implant cheaper black-market products areadministered totheanimals viainjection atundefined
parts oftheanimals 'bodies.
"(...) Ifhormonally active substances were authorized, thiswould probably alsoleadtoa
dramatic reduction ofthepossibilities toreveal suchamisuse withthehelpofdetected injection
sites, because therewould nolonger beindications toselect animals during thepost-and ante-
mortem examination thatareconsidered tobesuspicious ofahormonal treatment. Onthe
contrary, eachanimal would havetobecontrolled forinjecting sites. Since thisiscompletely
unrealistic, arandomised selection ofthecarcasses remains theonlycontrol forinjection sites.
Consumers could thusbesubject totheriskofeating undetected, maybe highly contaminated
injection sites.
"(...) Inthecontext ofapreventive protection ofconsumers 'health itshould beself-evident
totakethemisuse potential ofasubstance intoconsideration, when itisassessed forhealth
risks. Ifhealth risks toconsumers cannot beexcluded when asubstance ismisused, single
substances withanextreme misuse potential could alsobebanned evenifthesubstances are
nothazardous inthecaseofalegalapplication (...)."141
4.199 TheEuropean Communities indicated thattheprovisions ofEClawconcerning inspection and
control wereessentially contained inDirectives 85/358/EEC and86/469/EEC.142According tothese
Directives, theECmember States must present yearly inspection plans andyearly results oftheir
examinations, providing detailed descriptions of,interalia,random sampling ofselected liveand
slaughtered animals; investigation oflivesuspect animals andmeat withdetails ofthesubstances
searched for,thenumbers ofsamples planned andtaken, andtheanalytical methods used. TheEC
141B.Jülicher, "Sampling Strategies", in1995 ECScientific Conference Proceedings, pp.537-539. "Detection and
Surveillance", Working-Group III,idem,pp.33-34.
142ECOfficial Journal L191, 23July1985, p.46, andECOfficial Journal L275, 26September 1986, p.36. The
European Communities noted thatthese provisions have nowbeen reviewed, improved andre-enacted innewDirective
96/23/EC, of29April 1996, which willenter intoforce on1July1997.WT/DS48/R/CAN
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Commission ensured theconformity oftheyearly inspection plans withtheDirectives. Onaverage,
about 200,000 samples ofanimals were checked every yearintheEuropean Communities.
4.200 TheEuropean Communities claimed thatthesituation ofresidue controls andchecks inCanada
wasnotentirely clear. Itwould appear thatNational Programme Plans existed foreachyear, butonly
averylimited number ofsamples ofanimals were checked eachyear. Forexample, forzeranol it
wasforeseen thatsamples ofonly650animals would betested in1996. Fortrenbolone acetate samples
ofonly325animals, forMGA samples of275animals, andforthethree natural hormones samples
ofonly40animals.
4.201 TheEuropean Communities argued thattostatethathormones "are" implanted inthemiddle
thirdoftheanimal 'searwastobelieve that,under practical farmconditions, suchprecision wasa
matter ofroutine. TheEuropean Communities claimed thatfrom anexamination oftheCanadian
directivesforimplantationof"Compudose"implantscontainingoestradiolandoxytetracycline,published
inthe1995Compendium ofVeterinary Products inCanada, itwasillusionary tobelieve thatfarmers
could respect these procedures onaroutine basis when administering these hormones forgrowth
promotion. Another example constituted thedosage andimplantation directions for"REVALOR-S",
animplantcontainingbothtrenboloneacetateandoestradiolhormones,withnowithdrawaltimerequired,
which misleadingly stated that"allimplanted animals arevisually inspected upon arrival atthe
slaughterhouse". Other products containing zeranol, oestradiol andtestosterone inisolation orin
combinations were"Ralgro Ralabol" and"Synovex-H", forwhich nowithdrawal timewasrequired
andwhich improperly usedcould result inresidues ofthese hormones much higher thanthenaturally
produced hormones, exceeding tolerance levels. Infact,therewasnospecial identification ofimplanted
animals. Allanimals, implanted ornot,should indeed be"visually inspected" upon arrival ata
slaughterhouse, butthiswaspartofthenormal ante-mortem health inspection; ithadnothing todo
withhormone implants, which could notusually bedetected byvisual inspection. Discarding theear
atslaughter wasonlyuseful iftheimplant wasstillpresent intheear,butasasignificant proportion
ofimplants migrated toother parts ofthebody, itmight beirrelevant.
4.202 Canada claimed thattheECdiscussion ofadministration andusefailed toidentify anyrisk
posed bythesixhormones atissue when usedforgrowth promoting purposes inanimals. TheEC
argument focused onthefactthathormone implants were notadministered byveterinarians, inthe
mistaken assumption thatfarmers wereincapable ofadministering theseimplants themselves. Referring
toproceduresforadministeringhormoneimplants,theEuropeanCommunitiesbelittledfarmers,asserting
that"...itisillusionary tobelieve thatfarmers canrespect these procedures onaroutine basis when
administeringthesehormonesforgrowthpromotion".TheEuropeanCommunitiesprovidednoevidence
tosupport thisassertion.
4.203 Canadian producers routinely andeffectively administered treatments andvaccines forwhich
theiranimals 'health depended uponproper application. Theapplication ofgrowth promoting hormone
implants wasaroutine practice thatCanadian producers handled withahighlevel ofcompetence.
Moreover, itwould appear thattheEuropean Communities alsotrusted itsfarmers tohandle these
kinds ofrepetitious, technical tasks. Forexample, insome ECmember States, farmers didnotneed
aprescription toobtain vaccines thatwere administered tofood-producing animals byinjection.143
IntheUnited Kingdom, farmers didnotneedaprescription toobtain some localanaesthetics thatare
administered byinjection.144Presumably, these injections wereadministered bythefarmer without
thesupervision ofaveterinarian. Similarly, benzylpenicillin mustbeinfused intotheudder ofacow
143A.R.M. Kidd(September 1992), "Distribution ofVeterinary Medicines within theEuropean Community: Final Report
prepared forDGIIIoftheCommission oftheEuropean Communities" Table 6,p.48.
144Ibid.,Table 4,p.43.WT/DS48/R/CAN
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totreatmastitis. Benzylpenicillin wasavailable over-the-counter inatleastoneECmember State.
Again, presumably, these treatments were administered without thesupervision ofaveterinarian.
4.204 Canada stated itwasapparent thattheECpurported concerns withtheabuse andmisuse of
growth promoting hormones would apply equally, orwithgreater force, toavariety ofveterinary drugs
permitted foruseintheEuropean Communities. Forexample, withregard toMGA, administered
asanadditive infeedstuffs, theEuropean Communities stated that,"[f]or MGA there isawithdrawal
period of48hours priortoslaughter ...itshould notbetaken forgranted thattheprescribed withdrawal
period willalways berespected. ...substances which areproven tobecarcinogenic, ifallowed tobe
used, theyshould bedonesoonlyunder themoststrict conditions possible." InCanada 'sview, the
irony oftheECstatements wasthattheEuropean Communities allowed itsfarmers tousecarbadox
andolaquindox infeedadditives, without veterinary supervision, andwithout monitoring theresulting
residues (unless amember Statechose todoso).Bothsubstances weregenotoxic andrequired a28-
daywithdrawal period. AstheWorking Group ontheAssessment ofHealth Risks intheEC1995
Scientific Conference concluded:
"The antimicrobial drugs Carbadox andOlaquindox (called quinoxalines), possess genotoxic
and/or carcinogenic properties. Appreciable amounts ofresidues arefound intreated animals.
ADIvalues cannot yetbeestablished. Buttheirrestricted useinpigsonlyduring thefirst
fourmonths coupled withthespecified 28-day withdrawal period should leadtonegligible
residues atthetimeofslaughter andminimize theriskofexposure forconsumers. Thisimplied
safety feature requires theapplication ofgoodagricultural/veterinary practice which, however,
cannot completely beguaranteed, forexample, when slaughtering piglets, there isapotential
contradiction between theallowed dosage ofthedrugs upto4months ofageandarequired
withdrawal period of28days."145
4.205 TheEuropean Communities noted thatwithregard totheadministration anduseofhormones
thewhole issueofthecompeting interests involved hadbeenexplained byaworld expert onthisissue.
Dr.RoyHertz,M.D.,DirectoroftheNationalCancerInstitute'sEndocrinologyBranchfortwenty-eight
years andnowwiththeDepartment ofPharmacology attheGeorge Washington University Medical
Center, USA, wascitedbyOrville Schell, inhisbook Modern Meat:
"(...) tohaverigorously defended in1978 what hecalled theoestrogen-cancer hypothesis,
namely thatbothexogenous andendogenous oestrogens andtheirmetabolites playasignificant
andpossiblyetiologic[diseasecausing]roleinthepathogenesisofcancerinestrogen-responsible
tissues ofmanandanimal." (...)When pressed byacolleague tobemore specific about
thelevels ofexogenous estrogen thatmustexistinmeatbefore ariskofcancer totheconsumer
becomes really meaningful, Hertz replied simply, "The answer toyourquestion isthatwe
donotknow. (...)Iknow thatindustry people saythattheamount ofoestrogens theyare
adding toananimal 'ssystem arefarbelow levels thatnaturally occur afterconception. But
myresponse tothemis,"Fine. Butwhyaddmore?" Thenatural surges ofhormones arealready
enough ofabiological burden onthebody. Weknow thatthese endogenous hormones already
playavitalroleinthedevelopment ofmalignancies inthefemale genital tracts andinthebreast.
So,justbecause these chemicals arepresent inthebodydoesn 'tjustify burdening itwitheven
more, particularly when theamounts thatareeffective areinmicrogram quantities. Withregard
tobirthcontrol pillsthere aretwoconditions thatmake thecircumstances verydifferent ...
thefirstisthatcontraceptives aretaken under thesupervision ofadoctor. Thesecond isthat
when aconsumer decides totakethem, sheismaking afreechoice, presumably withfull
knowledge ofthealternatives andthepossible adverse effects. Butinthecaseofhormonal
foodadditives, theconsumer hasnoideathatheorsheisingesting them. AndIsimply don't
1451995 ECScientific Conference Proceedings, pp.24 to25.WT/DS48/R/CAN
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seeanyreason whyaperson should beinvoluntarily exposed tothem. Isimply takeapurist
viewabout these kinds offoodadditives ...unless there isacompelling need-inthecaseof
famine, forinstance -Idon'tthink theactual, orevenpotential, riskcanbejustified. For
drugcompanies topresent thesecompounds asbeing without risk...iscompletely outoforder,
since wedon'treally know whattheirlong-term cancer-causing consequences willbe."
4.206 TheEuropean Communities asserted thatforthesubstances benzylpenicillin andivermectin,
Article4(3)(b)ofDirective81/851/EEC,asamendedbyDirective90/676/EEC146,requiredaprescription
byaveterinarian forthedispensing tothepublic ofveterinary medicinal products inorder toavoid
riskstoconsumersoffoodstuffsobtainedfromtreatedanimals.IfinsomememberStatesnoprescription
waseffectively required, thiswasnotinconformity withtheprovisions ofthisDirective. TheEC
Commission hadrequested theinformation from allECmember States, butnotallofthem hadyet
replied. Thesituation ofthose which hadreplied wasasfollows: inGermany andDenmark neither
ofthese twosubstances could beobtained without prescription. Canada admitted thatprescription
wasalsorequiredinFrance.IntheNetherlands,benzylpenicillinwassubjecttoveterinarianprescription.
Ireland hadnotyetreplied, buttheCommission disposed ofinformation which showed thatonly
benzylpenicillin wasavailable without prescription andonlytofarmer organisations carrying outa
special programme fortheprevention ofmastitis incows. Thisprogramme wascarried outunder
veterinary supervision toalimited number ofanimals. TheEuropean Communities argued thatCanada
hadmade suchawidereference tosomany substances, thatitwasdifficult tofollow where itsargument
wasleading thelegaldiscussion. Progressively, Canada hadconfined theissueofconsistency tovery
fewsubstances anditappeared thatthere were twoofthem onwhich Canada hadconcentrated its
arguments: carbadox andolaquindox, because theyweresaidtoposethesame typeofriskstohuman
andanimal health. TheEuropean Communities hadexplained theconditions under which carbadox
andolaquindox wereallowed tobeusedintheEuropean Communities. Onthebasisofthedifferences
stressed bytheEuropean Communities, itcould beargued thatcarbadox andolaquindox weredifferent
substances fromthehormones atissue. They wereadministered toonetypeofanimals only(piglets)
andtheyacted onlyindirectly asgrowth promoters. Theconditions imposed bytheECmeasures
guaranteed, however, thatthere were noresidues ofcarbadox andolaquindox inmeat destined for
human consumption. Sothelevelofprotection wasthesame withregard tothese twosubstances and
thehormones. TheEuropean Communities hadshown thatitwould notbeabletoguarantee thesame
level ofprotection forthese hormones, haditdecided tofollow theCodex MRLs. Inthecaseof
carbadox andolaquindox, theEClevelofprotection wasalsonorisksfromresidues ofthesehormones
inmeatdestined forhuman consumption. Butthefactthatithadchoosen toapply thislevelofprotection
bymeasures different fromthose thatitapplied togrowth hormones wasirrelevant tothisPanel. The
European Communities choose itsmeasures inthelightofthespecific circumstances inwhich each
substance wasusedinorder toachieve itsappropriate levelofprotection.
4.207 TheJECFAscientificreportoncarbadoxandolaquindoxwasdatedfrom1991.Ithadconcluded
thatalthough carbadox wasacarcinogenic chemical substance, theresidues ofthemetabolites which
could bedetected inthemuscle ofpigmeat, iftheconditions ofusewere respected, were not
carcinogenic. Itwasonthisevaluation thatJECFA hadauthorized theuseofcarbadox. TheEC
legislation respected alltheconditions ofuseindicated intheJECFA report. Onolaquindox, the
conclusions oftheJECFA report were notconclusive andfurther studies hadbeen requested. But
theprovisional useofolaquindox under good practice intheuseofveterinary drugs wasallowed.
TheEClegislation respected theconditions ofuseforolaquindox. TheEuropean Communities had
allowed theuseofcarbadox andolaquindox since 1988. AttheCouncil ofMinisters of26February
1996, thedecision hadbeentaken toreview theauthorizations ofanumber ofsubstances among which
were carbadox andolaquindox. Thishadbeenconfirmed intheCouncil ofMinisters meeting of
146ECOfficial Journal L373, 31December 1990, p.15.WT/DS48/R/CAN
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16December 1996. Thisshowed thattheEuropean Communities wasalready taking action onthese
twosubstances onitsowninitiative.
(vi) Other parameters
4.208 TheEuropean Communities argued thatapotential source ofriskfrequently mentioned by
scientists stemmed from uncertainty about thenature andreliability ofthemethods usedtoestablish
therelevant data. Theprocedure forcharacterising theriskfrom theuseofhormones hadremained
largely unchanged for30-40 years andscientists hadargued thattheprocess ofthescientific assessment
oftheriskshould draw onthescience basetoassess therisk,thenaddress uncertainties, rather than
fusethese twoelements together. However, amuch sounder scientific approach wastoencourage
strongly theinvestigation ofthemechanism oftoxicity ofeachnewpromoter. Unless more effort were
directed tounderstanding whyaparticular adverse effect ofconcern occurred (i.e.assessment ofthe
mechanism oftoxicity), riskassessment would always bevulnerable tothecriticism thatitsscientific
basiswasflawed. Science continued tomake rapid advances andnoriskassessment could beregarded
asthedefinitive statement foralltime. Aregular review procedure wasneeded, thefrequency ofwhich
shouldbedeterminedbysuchfactorsastheavailabilityofnewtoxicologicaldata;thelevelofuncertainty
identified intheproducts 'riskassessment; andfindings from exposure monitoring investigations.
Alltoooften, further investigations oftheriskceased atthepoint atwhich aparticular promoter was
either accepted foruseorrejected. Means ofprogressing theknowledge base, intheareas where
substantial uncertainties existed, hadtobefound.147
4.209 TheEuropean Communities alsoargued thatscientists raised concerns withregard tothe
confidentiality ofdata. Ithadbeensuggested thataseparate riskassessment must beconducted on
eachgrowth promoting substance drawing onalltheavailable data, notsimply thatprovided bya
company wishing tomarket aproduct. Thisrequired improved accessibility toinformation classified
asconfidential. Forthispurpose, ithadbeen suggested thatatime-limit should besetonthe
confidentiality ofsafety data.148TheEuropean Communities didnotdispute thefactthatthese were
limits toscience. However, those limits should betaken intoaccount when assessing risks. Members
should beabletolearn frommistakes ofscience inthepastandtakethemintoaccount insetting their
sanitary policy objectives; should beabletoapply acautious sanitary policy notdictated bynarrow
economic reasons; andshould notbedeprived fromexercising theirsovereign righttotakeappropriate
SPSmeasures, simply because Codex haddecided (by33votes infavour and29against, with
7abstentions, outofatotalmembership of152countries) torecommend ADIs andMRLs forthese
hormones forgrowth promotion.
(vii) Theprecautionary principle
4.210 TheEuropeanCommunitiesstressedthatthedifferenceindegreeofregulationbetweenCanada
andtheEuropean Communities wasduetothegreater attachment oftheEuropean Communities to
theprecautionary principle.149Itreflected thedifferent levels ofconsumer protection adopted bythe
European Communities andCanada. Where there existed adoubt overthesafety ofaproduct, the
European Communities hadgiven thebenefit ofdoubt totheconsumer, especially incases where the
potential risks might affect verylarge parts ofthepopulation. Canada had,inthecaseofgrowth
hormones, given ittotheproducer.
147Prof. JimBridges andDr.OlgaBridges, "Hazards ofGrowth Promoting Agents andStrategies ofRiskAssessment",
1995 ECScientific Conference Proceedings, pp.258-259.
148Ibid.,p.262
149D.Freestone &E.Hey(1996), "The Precautionary Principle andInternational Law".WT/DS48/R/CAN
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4.211 Thisdifference indegree ofregulation wasduetothegreater attachment oftheEuropean
Communities totheso-called precautionary principle.150Thisprinciple wasnowinscribed intheEC
Treaty itself, ofwhich Article 130R ontheprotection oftheenvironment provided, interalia:
"Communitypolicyontheenvironmentshallaimatahighlevelofprotectiontakingintoaccount
thediversity ofsituations inthevarious regions oftheCommunity. Itshallbebased onthe
precautionary principle andontheprinciples thatpreventive action should betaken, that
environmental damage should asapriority berectified atsource andthatthepolluter should
pay. Environmental protection requirements must beintegrated intothedefinition and
implementation ofother Community policies ..."151
4.212 Torefertoitasaprecautionary "principle"152or"approach" wasoflittleimportance inthe
ECview. Itsessential features werewellknown andwidely accepted soastosaythatithadreached
thestatus ofagenerally accepted principle ofinternational law,particularly intheareaofprevention
ofrisks tohuman oranimal health ortheenvironment. Thehazard (cancer) hadbeenidentified in
thiscase; lackofscientific knowledge ontheexactmechanisms bywhich itoperated wasnotasufficient
excuse forfailing totakestrict measures toprevent it.
4.213 TheEuropean Communities observed thattherewasawider angle fromwhich theserisksmight
beexamined andwithin abroader regulatory context. Thecrucial rolescience played inregulating
theuseoftoxic substances anddrugs wasbeyond doubt; theEuropean Communities usedscience
intheir regulatory process andpromoted itsroleinternationally. Buttheuseofscience hadits
limitations. Scientific certainty inaregulatory process wasdifficult toachieve andregulating toxic
substances hadtobedoneinthiscontext ofuncertainty. Intheend,thequestion washowmuch of
thatuncertainty alegalsystem wasprepared toaccept. TheECprecautionary approach wasrequired
toavoid situations asthose portrayed bymany cases ofhealth hazards which onlybecame apparent
longafter substances orproducts hadbeen assumed tobesafe, such asCyclamates, saccharin,
phehformin, numerous pesticides (e.g., DDT), asbestos, thalidomide, hormone DES. Twocases of
recentinterestintheEuropeanCommunitiesillustratedthedesirabilityoftakingaprecautionaryapproach
toconsumer protection: E.ColiandBSE.153
150Ibid.
151TheEuropean Communities noted thattheprecautionary principle hadacquired recognition inseveral international
lawagreements andconventions. E.g., theUnited Nations Conference onEnvironment andDevelopment (UNED): Rio
DeclarationonEnvironmentandDevelopment,13June1992,UNDoc.A/CON.151/26,Vol.I(1992).Ingeneral,Freestone
&Hey, above.
152TheEuropean Communities referred toachapter ofarecent book byD.Freestone andE.Hey, ThePrecautionary
Principle andInternational Law, 1996, which clearly concluded thattheprecautionary principle hadalready reached the
status ofageneral principle ofinternational law(Chapter 3byJ.Cameron andJ.Abouchar, TheStatus ofthePrecautionary
principle inInternational Law.
153TheEuropean Community explained thatE.Coliwasabacterium which inhabited theintestines ofallanimals. In
theearly daysoffoodbacteriology ithadbeenassumed tobeubiquitous andharmless. InthefirstFAO monograph onmeat
hygiene, published in1957, itwasstated that:"There arenotconvincing reports which directly implicate E.Coliinoutbreaks
offoodpoisoning". Thesecond report oftheJoint FAO/WHO Expert Committee onMeat Hygiene (1962) hadconsidered
thatknowledge oftheimportance ofE.Coliincausing food-borne disease waslacking andshould beinvestigated. Even
in1974, Thornton 'sTextbook ofMeat Hygiene stated thatanimal strains ofE.Coli were "unlikely tobecome established
inthehuman bowel". When theEuropean Communities, in1964, hadadopted itsfirstrules onmeat hygiene, ithadtaken
aprecautionary approach, requiring hygienic structures, equipment andhandling procedures withaview topreventing all
bacterial contamination ofmeat.
With regard toBSE, theEuropean Communities noted thatthiswasanewdisease ofcattle. Ithadbeen first
recognised intheUnited Kingdom only10years ago. When ithadbeenfound tobeamember ofthegroup oftransmissible
(continued...)WT/DS48/R/CAN
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4.214 Canada argued thattheprecautionary principle hadnotyetattained thestatus ofageneral
principle ofinternational law,northatofaruleofcustomary international law.154When theSPS
Agreement wasbeing negotiated, governments were aware oftheprecautionary approach asitwas
being developed inthefieldofinternational environmental law. Theinclusion ofArticle 5.7inthe
SPSAgreement, which permitted Members toproceed withtheadoption ofprovisional measures on
thebasis ofavailable pertinent information, wasanexpression oftheprecautionary approach inthe
SPSAgreement. Thustheprecautionary approach hadbeentaken intoaccount when theinternal balance
ofrights andobligations within theSPSAgreement hadbeenstruck.
4.215 TheEuropean Communities argued thatArticle 5.7wasnotapplicable tothiscasebecause
theECmeasures werenottemporary. TheEuropean Communities knew about thehazards andhad
taken measures toprevent it.Infact,there wasclearevidence, from IARC, JECFA andothers that
these hormones were carcinogens. TheEuropean Communities were therefore justified inacting.
4.216 Canada observed thattheEuropean Communities hadconceded thattheirimport banwasnot
based Article 5.7.However, theEuropean Communities appeared tosuggest thattheprecautionary
conceptcouldsomehowoverridecertainprovisionsinthetextoftheSPSAgreementandCanadarejected
anysuchsuggestion. Anyintimation bytheEuropean Communities thattheprecautionary concept
would somehow justify theadoption ofmeasures under theSPSAgreement thatwere notbased on
scientific evidence rancounter tofundamental canons oftreaty interpretation laiddown inArticles 31
and32oftheVienna Convention ontheLawofTreaties andwould amount toarevision oftheSPS
Agreement. Thus, theprecautionary approach orprinciple could notbeinvoked bytheEuropean
Communities tooverride theobligations oftheSPSAgreement.
(viii) Animal health protection
4.217 TheEuropean Communities argued thatoneoftheaimsofthemeasures atissuewastoprotect
animals from theuseofthese hormones forgrowth promotion. Inthepreparatory discussions, the
European Parliament hadconsidered "thepossible adverse effects ofthese substances ontheimmunity
against various diseases ofanimals andthatthisinturnmayleadtoanincreased useofantibiotics".155
Furthermore,thepreambleandtextofDirective88/146/EECclearlyestablishedthatconcernsofpotential
riskstoanimal health were alsotaken intoaccount. Thestrict conditions imposed bytheDirective
153(...continued)
spongiform encephalopathies, ithadbeen widely assumed tobethebovine form ofscrapie, adisease ofsheep recognised
forover250years. Asthere wasnoevidence ofadanger tohuman health from eating meat from scrapie-affected sheep,
ithadbeen assumed insome quarters thatthere would similarly benodanger tohumans from BSE. Thatassumption had
recentlybeenchallengedbytheappearanceofaclusterofcasesofanewformofCreutzfeldt-Jakobdisease,ahumanspongiform
encephalopathy, which experts considered waslikely linked toBSE. Inthiscase, itwasfortunate thataprecautionary approach
wastaken atanearly stage, despite thegenerally heldview thatanyrisktohumans wasuncertain orextremely small. The
tissues known tocontain theBSEagent, aswellassome inwhich infectivity hadnotbeen demonstrated butwhich could
possibly beaffected, were removed from thehuman foodchain. Atthetime, thisaction wascriticised insome quarters as
anover-reaction butitnowappeared tohave been far-sighted.
154Canada citedBirnie andBoyle, whointheirwork entitled "International LawandtheEnvironment" (Oxford: Clarendon
Press, 1992), p98,arrived atthefollowing conclusion regarding the"precautionary principle":
Despite itsattractions, thegreat variety ofinterpretations given totheprecautionary principle, andthenovel and
far-reaching effects ofsome applications suggest thatitisnotyetaprinciple ofinternational law.Difficult questions
concerning thepoint atwhich itbecomes applicable toanygiven activity remain unanswered andseriously undermine
itsnormative character andpractical utility, although support foritdoesindicate apolicy ofgreater prudence on
thepartofthose states willing toaccept it.
Although thiswaswritten in1992, Canada submittted thatthisconclusion wasstillvalid.
155European Parliament 'sResolution, ECOfficial Journal, No.C288/158, 11November 1985.WT/DS48/R/CAN
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ontheuseofthese hormones fortherapeutic andzootechnical purposes hadasoneofitsobjectives
theprotection ofanimal health from improper administration. Article 5provided thatECmember
States mustensure that"noanimals aredispatched fromtheirterritory tothatofanother Member State
which havehadadministered totheminanywaywhatsoever substances withathyrostatic, oestrogenic,
androgenic orgestagenic action ...",except fortherapeutic orzootechnical purposes. Article 6.1
provided that"member States shallprohibit importation from thirdcountries ofanimals andofmeat
fromanimals towhich havebeenadministered inanywaywhatsoever substances withathyrostatic,
oestrogenic, androgenic orgestagenic action", except fortherapeutic orzootechnical purposes and
under conditions equivalent tothose applied intheEuropean Communities. Oneobjective ofthis
prohibition wastoprotect animal health, since theprohibition ontrade insuch animals clearly
discouraged theadministration ofthese hormones inthefirstplace.
4.218 TheEuropean Communities claimed thatscientists agreed thatdoses ofthesehormones atlevels
which produced ahormonal activity werecarcinogenic tolaboratory animals. The1988JECFA Report
haddocumented these carcinogenic effects. Ithadreported thatoralandparenteral administration
ofoestradiol-17 could increase theincidence oftumours inexperimental animals. These tumours
largelyoccurredintissueswithhighlevelsofspecifichormonereceptorswhichwerenormallyresponsive
tostimulation byoestradiol-17 .JECFA hadalsonoted thattheincidence oftumours ofthemammary
gland, ovary, uterus andvagina werehigher inanimals treated withprogesterone alone thanincontrol
animals.Theincidenceofuterinetumourswas"surprisinglyhigh"andtheincidenceofprostatictumours
washigher inrodents treated withhighdoses oftestosterone, thanincontrol animals. JECFA concluded
thatthecarcinogenic responses wererelated tothehormonal activities ofeachofthesethreehormones.
4.219 TheEuropean Communities noted thatJECFA hadalsofound liverhyperplasia andtumours
inmicefedhighdoses oftrenbolone acetate andslight increases intheincidence ofislet-cell tumours
ofthepancreas ofrats,which JECFA concluded arose asaconsequence ofthehormonal activity of
thetrenbolone metabolites. TheJECFA review ofzeranol noted oestrogenic butnotcarcinogenic effects
inrats. Inmice, however, higher incidence ofanterior lobetumours ofthepituitary gland occurred
thaninmice inthenegative control group. JECFA reported thatsuchtumours rarely occurred
spontaneously inmicebutwereknown toresult fromadministration ofoestrogenic hormones. JECFA
again concluded thatthetumorigenic effect ofzeranol wasassociated withitsoestrogenic properties.
4.220 Thevarious carcinogenic effects mentioned bythe1988JECFA Report onlaboratory animals
wereexplained more fullyinthereports oftheInternational Agency forResearch onCancer (IARC).
IARC Monograph, Supplement 7,1987, reported sufficient evidence ofcarcinogenicity toanimals
fromoestradiol-17 andprogesterone. IARC noted that"[a]dministration tomiceofoestradiol-17
anditsesters increased theincidence ofmammary, pituitary, uterine, cervical, vaginal, testicular,
lymphoid andbonetumours. Inrats,there wasanincreased incidence ofmammary and/or pituitary
tumours. Inhamsters, ahighincidence ofmalignant kidney tumours occurred inintact andcastrated
males andinovariectomized females, butnotinintact females. Inguinea-pigs, diffuse fibromyomatous
uterine andabdominal lesions wereobserved" (page 284). IARC reported thatprogesterone "increased
theincidence ofovarian, uterine andmammary tumours inmice. Dogs treated withprogesterone for
fouryears developed adose-related incidence ofmammary-gland nodules" (page 296). Importantly,
IARC indicated thattherewasevidence thatlowdoses ofprogesterone administered overlongperiods
acted incombination withcarcinogenic agents, suchassome viruses orchemicals, toenhance tumour
developments. Therefore, long-term administration ofsynthetic progestins could produce acomparable
hazard byincreasing theincidence oftumours duetoother agents.156
15621IARC Monographs, p.132.WT/DS48/R/CAN
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4.221 TheIARC hadalsofound thatzeralenone, ametabolite ofzeranol, inthedietoflaboratory
animals hadcarcinogenic effects157,andhadcaused other effects, including:
"...atrophy oftheseminal vesicles andtestes, squamous metaplasia oftheprostate gland,
osteopetrosis,myelofibrosisofthebonemarrow,cytoplasmicvacuolizationoftheadrenalglands,
hyperkeratosisofthevaginaandendometrialhyperplasia...pseudopregnancy[and]infertility."158
Inaddition, consumption ofzeralenone bypregnant animals caused areduction infetalweight and
anincreased prevalence ofskeletal problems andincidence ofstillbirths.159Asregards thecarcinogenic
effects ofthehormone MGA, published datadocumented theinduction ofastatistically significant
incidence ofmammary tumours infemale mice.160
4.222 Inconclusion, theEuropean Communities submitted thatalmost allthearguments thatwere
made above (paragraphs 4.151 to4.209), especially thepossible carcinogenic effects andtheriskswhich
might arisefromanadministration ofhormones notinaccordance withgoodveterinary practice, were
equally applicable toanimals.
4.223 Canada argued thatitemerged from thedefinition ofsanitary measures inAnnex Aofthe
SPSAgreement thatasanitary measure wastaken toprotect human oranimal lifeorhealth within
theterritory oftheMember .TheECprohibition ontheimportation ofhormone-treated beefdidnot
protect thehealth orlifeofcattle intheterritory oftheEuropean Community. Thus, the
European Communities 'references toanimal health issues wereirrelevant tothisdispute andshould
begivennoconsideration.Moreover,Canada'scomplaintwaslimitedtothenullificationandimpairment
ofbenefits accruing toCanada pursuant totheWTO Agreements respecting market access formeat,
andmore specifically forbeef. Canada exported livestock totheEuropean Communities forbreeding
purposes onlyand,since thistypeoflivestock wasnottreated withhormones forgrowth promotion,
Canada 'sexports totheEuropean Communities were notaffected bytheECmeasures atissue.
(j) Article 5.4
4.224 TheEuropean Communities noted thatArticle 5.4stated that,inchoosing theappropriate
levelofprotection, Members "should ...takeintoaccount theobjective ofminimizing negative trade
effects". Anearlydraftofthisprovision required countries toconsider theeffect ontradeofthelevel
theychose, butinthefinalversion ofthetextthemandatory language hadbeenrejected. Acomparison
ofArticles 5.2and5.3oftheSPSAgreement alsomade itclear thatwithrespect tohuman health
risks, economic factors were irrelevant toriskassessment orthedetermination oftheappropriate
measures tobeusedtoprotect against suchrisks.
(k) Article 5.5
4.225 Canada recalled thatArticle 5.5oftheSPSAgreement required that"...eachMember shall
avoid arbitrary orunjustifiable distinctions inthelevels itconsiders tobeappropriate indifferent
situations, ifsuchdistinctions result indiscrimination oradisguised restriction oninternational trade".
Canada claimed, however, thattheEClevel ofsanitary protection forgrowth promoting hormones
15756IARC Monographs, p.431; and31IARC Monographs, p.287.
15856IARC Monographs, p.417.
15956IARC Monographs, pp.421-422.
160J.W. Lauderdale etal.(1977), "Studies ofaprogesterone (MGA) asrelated toresidues andhuman consumption,"
Vol.3, pp.5-33.WT/DS48/R/CAN
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wassignificantly higher thantheEClevel forantimicrobial growth promoters andother veterinary
drugs, resulting indiscrimination andadisguised restriction oninternational trade.
4.226 Canada noted thataveterinary drugwas"[a]ny substance applied oradministered toanyfood-
producing animal, suchasmeatormilkproducing animals, poultry, fishorbees, whether usedfor
therapeutic, prophylactic, ordiagnostic purposes, orformodification ofphysiological functions or
behaviour".161Alargenumber ofveterinary drugs wereusedinfarmanimals andcould becategorized
intoanumber ofclasses, including antimicrobials (e.g.,antibiotics), anthelmintics, pesticides,
antiprotozoals (e.g.,coccidiostats) andhormones. Thefateoftheseveterinary drugs within theanimal
body washighly variable. Some compounds weremetabolized oreliminated quickly, while others,
suchassome antibiotics, were much more persistent. Hormones were onlyonetypeofveterinary
drugusedforgrowth promotion. Antimicrobial feedadditives werealsocommonly usedasgrowth
promoters inanumber ofanimal species, including cattle. Growth promoters suchasionophores (e.g.,
monesin) andnon-ionophore antibiotics (e.g.,avoparcin, carbadox, olaquindox) wereusedextensively
asfeedadditives inallECmember States.162
4.227 Canada argued thattheECmeasures must beconsidered inthecontext oftheEuropean
Communities'regulationofveterinarydrugsingeneral.TheEuropeanCommunitiesregulatedveterinary
drugs under twoschemes: products intended fortherapeutic useorforthealteration ofphysiological
function163andthose added tofeedforprophylaxis andgrowth promotion.164Canada noted thatthere
appeared tobenotable differences between thetwoschemes. Veterinary drugs governed bythe
Veterinary Medicines Directives weresubject toauthorization procedures andMaximum Residue Limit
("MRL") requirements165("MRLs Regulation") andtotheresidues monitoring requirements.166This
implies thatthere wasanaccepted levelofriskintheuseofeachofthese compounds. Incontrast,
veterinary drugs governed bytheFeed Additives Directives didnotappear tobesubject tothese
provisions. MRLs werenotestablished forthese other products, despite thefactthattheyposed some
human health risks. Thethreenatural hormones atissue-oestradiol-17 ,progesterone andtestosterone
-could onlybeusedfortherapeutic andzootechnical purposes intheEuropean Communities. Their
usewasgoverned bytheVeterinary Medicines Directives, andtheyweresubject totheauthorization
proceduresandMRL requirementssetoutintheECMRLsRegulations,andthemonitoringrequirements
setoutinDirectives 85/348/EEC and96/23/EC.
4.228 Canada indicated thattheECVeterinary Medicines Directives laiddown rulesformarketing
authorizationanddistributionofveterinarymedicinalproducts.Anapplicationforauthorizationrequired
studies oftoxicity, pharmacological properties, residues andtheireffects, anddataontheemergence
ofresistant organisms inthecaseofproducts usedfortheprevention ortreatment ofinfectious disease
161Codex Alimentarius,Vol. 3:"Residues ofVeterinary Drugs inFoods", 2nded.(Rome: FAO, 1996) pp.77.
162Canada explained thatfeedadditives areincorporated intofeedingstuffs fororalanimal feeding. Substances usedin
accordance withtheFeedAdditives Directives areavailable, intheEuropean Communities, without aveterinary prescription.
163Regulated under Directives 81/851/EEC and81/852/EEC andtheiramendments ("Veterinary Medicines Directives",
including: Directive 81/851/EEC; Directive 81/852/EEC andDirective 93/40/EEC.
164Regulated under Directive 70/524/EEC anditsamendments, "Feed Additives Directives", including Directive
70/524/EEC; Directive 84/587/EEC; Directive 93/113/EC; Directive 93/114/EC andDirective 96/51/EC. Directive
91/248/EC appears tocontain themost recent consolidation oftheannexes totheFeed Additives Directives.
165SetoutinRegulation 2377/90/EEC anditsamendments.
166SetoutinDirectives 86/469/EEC and96/23/EC ("Residues Directives").WT/DS48/R/CAN
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inanimals. TheCommittee forVeterinary Medicinal Products167gaveopinions onwhether aparticular
medicinal product complied withtheDirective 'srequirements.
4.229 Canada stated thatECmember States wereobliged totakeregulatory measures tocontrol the
distribution ofveterinary drugs inaccordance withtheVeterinary Medicines Directives. Canada noted
that,nonetheless, implementation differed among ECmember States, withsome permitting certain
veterinary medicines foruseinfoodanimals tobeavailable without prescription, while others made
itsubject toaprescription.168There were alsodivergent views onwhen itwasnecessary fora
veterinarian toadminister aprescribed drug.169Although ECDirectives dictated thatonlyaveterinarian
canadminister thethreenatural hormones, itappeared thattheEuropean Communities didnotextend
thatrequirement tocover other drugs, suchasgeneral anaesthetics, narcotics orpsychotropics.170In
practice, farmers might beadministering prescribed veterinary drugs without theveterinarian even
seeing theanimals being treated.171
4.230 Canada noted thatunder theECMRLs Regulations, nonewveterinary medicinal product might
beauthorized foruseinECmember States untilaCommunity-wide MRL hadbeenset,andMRLs
forexisting products were tobeestablished before theendof1997. Allpharmacologically active
substances considered must beentered intooneoftheannexes totheRegulation172,which were as
follows:
(i) substances forwhich MRLs havebeenfixed;
(ii) substances notsubject toMRLs;
(iii) substances forwhich provisional MRLs havebeenfixed;
(iv) substances forwhich noMRLs canbefixed.
4.231 Substances wereincluded inAnnex IIwhere, "...following anevaluation ...itappears that
itisnotnecessary fortheprotection ofpublic health toestablish amaximum residue limit". For
substances contained inAnnex III,aprovisional MRL hadbeenestablished foradefined period of
time"...provided thatthere arenogrounds forsupposing thatresidues ofthesubstance concerned
atthelevel proposed present ahazard tothehealth oftheconsumer". Substances were entered in
Annex IVwhere itappeared thataMRL could notbeestablished because residues ofthesubstance,
atwhatever limit, infoodstuffs constituted ahazard tothehealth oftheconsumer. Theadministration
ofthese substances wereprohibited intheEuropean Communities foruseinfood-producing species.
Ofthethreenatural hormones atissueinthisdispute, onlyoneappeared tohavebeenconsidered under
thisRegulation, oestradiol-17 ,which hadbeenincluded inAnnex II.TheEuropean Communities
haddecided thatitneednotbesubject toaMRL.
167Established byDirective 81/851/EEC.
168A.R.M. Kidd, Distribution ofVeterinary Medicines Within theEuropean Community: Final Report prepared for
DGIIIoftheCommission oftheEuropean Communities (September 1992) p.25 (hereinafter Distribution ofVeterinary
Medicines Within theEuropean Community: Final Report). SeealsoA.R.M. Kidd, "Distribution ofveterinary drugs within
theEuropean Union" (1994) 8:2Vet.Drug Reg. Newsletter 35,pp.35-38.
169Distribution ofVeterinary Medecines Within theEuropean Community: Final Report, note33,Table 6,p.47.
170Distribution ofVeterinary Medicines intheSingle Market.
171Canada indicated thatthiswasthecaseinGermany, forexample.
172ECVeterinary Medecine Directorate, "Regulation 2377/90: Consolidated Annexes".WT/DS48/R/CAN
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4.232 CanadaindicatedthattheEuropeanCommunitieshadestablishedrequirementsfortheexamination
ofanimalsandfreshmeatforthepresenceofveterinarydrugresidues173which,withrespecttohormones,
supplemented requirements174setting outrules onthedetection andmonitoring ofsubstances having
ahormonal orthyrostatic action. ECmember States wererequired totestforthepresence ofveterinary
drugresidues under a"National Plan". ECReference Laboratories andNational Laboratories provided
surveillancetestingofmeatsamples.Whereanexaminationofasamplerevealedthepresenceofresidues
ofprohibited substances orquantities ofauthorized substances exceeding thelevels setbyEClawor,
intheirabsence, national levels, competent authorities wererequired tofollow upwithaninvestigation
andappropriate measures. Canada added thatasof1July1997, Council Directive 96/23/EC, would
replace thepresent legislation, setting outmeasures tomonitor listed substances andgroups ofresidues.
ThisDirective appeared tobroaden thescope oftherepealed Directives "tocover other substances
which areusedinstockfarming topromote growth andproductivity inlivestock orfortherapeutic
purposes andwhich mayprove dangerous totheconsumer onaccount oftheirresidues".175
4.233 Canada recalled thattheEuropean Communities regulated feedadditives differently thanother
veterinary drugs. However, antimiciobial feedadditives wereamong those animal husbandry drugs,
called growth promoters, usedforimproving animal production without aprimary therapeutic objective.
Better weight gainand/or feedefficiency werethemain goals.176Antimicrobial feedadditives were
antimicrobial compounds which changed thepopulation ofmicroorganisms inthealimentary tractof
healthy animals, resulting inimproved feedconversion efficiency andhence growth rate.177Hormones,
incontrast, exerted theireffects aschemical messengers which bound tospecific receptors.178
4.234 There wereanumber ofgrowth promoting antimicrobial compounds thatwereadministered
inthefeedatlowdoserates. These compounds could besub-divided intocategories ofionophore
antibiotics (e.g.,monesin, lasalocid), non-ionophore antibiotics (e.g.,carbadox, avoparcin) andgut
activegrowthpromoters(e.g.,probiotics,enzymes).Theionophoreantibioticsaltereddigestion,whereas
thenon-ionophore antibiotics might favourably modify thequantity andquality ofnutrients entering
thebody.179Coccidiostats were another group ofantimicrobial feedadditives usedforprophylaxis
purposes. Coccidiosis wasahighly contagious infection ofananimal caused byparasitic microbial
organisms (i.e.,protozoa) collectively known ascoccidia. Thisdisease affected mainly poultry, but
alsocattle, pigs, sheep andgame birds. Asmany oftheantimicrobial feedadditives werefedtothe
animals throughout theirlives, itwaspossible thatother veterinary drugs would beadministered in
combination, oratthesame time, asthefeedadditives were being administered.
4.235 Antimicrobial agents wereadded toanimal feeds fortwopurposes: (1)growth promotion, or
(2)tocureorprevent outbreaks ofdisease. OneECscientist hadindicated that"[i]thasbeenestimated
173Directive 86/469/EEC.
174Directive 85/358/EEC.
175Council Directive 96/23/EC, preamble.
176VanDerWal, P.&Berende, P.L.M. "Effects ofanabolic agents onfoodproducing animals" in,"Anabolics inAnimal
Production: Public health aspects, analytical methods andregulation", OIESymposium (Paris, 15-17 February 1983), p.72.
177Crosby, N.T., "Determination ofVeterinary Residues inFood", EllisHorwood Series inFood Science andTechnology,
pp.33-36, p.34 (hereinafter "Determination ofVeterinary Residues inFood").
178Brander, G.C. etal.,eds., "Veterinary Applied Pharmacology &Therapeutics", 5thed.(London: Bailliere Tindall,
1991), p.279 (hereinafter Veterinary Applied Pharmacology &Therapeutics).
179P.Schmidely&M.Hadjipanayiotou,"GrowthPromotersforFatteningKids,"inP.Morand-Fehr,ed.,"GoatNutrition"
(Pudoc Wageningen, 1991) p.184.WT/DS48/R/CAN
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thatapproximately one-third ofallUKfeeding stuffs contain medicinal compounds licensed forinclusion
without aveterinary prescription, whilst only5percentoffeeds contain medicaments fortherapeutic
use".180Theprimary usesthuswereforprophylaxis purposes, thatis,toprevent disease outbreaks,
orforgrowth promoting purposes.181
4.236 CanadaarguedthatthedistinctionsmadebetweentheECregulatoryschemesgoverningveterinary
drugs ontheonehand, andfeedadditives ontheother, were anomalous.182Atajointmeeting of
ECCommission DGIII andDGVI heldunder theauspices oftheScientific Committee onAnimal
Nutrition (SCAN)183,oneECscientist hadcommented that:
"SCAN ...hasseencertain benefits infollowing theMRL route inassuring consumer safety.
Notleast among these aretheuseoftheMRL forestablishing withdrawal periods for
70/524/EEC candidate compounds andforresidues surveillance.
Thisisimportant nowastheJECFA system makes nodistinction between veterinary medicines
andmedicinal feedadditives anditrecently assessed twodrugs, carbadox andolaquindox,
currently regulated intheCommunity under 70/524/EEC andsonotsubject toMRLs under
2377/90. Indoing soitestablished anMRL forcarbadox andidentified further work on
olaquindox. (...)Inviewing MRLs within theCommunity, itseems onlysensible toview
medicines asonedistinct group -rather thantoseethem, asiscurrently thecase, largely as
therapeutics andfeedadditives -andtoestablish MRLs forall.Thiswould introduce some
degree ofharmonisation onthisfront withtheJECFA/Codex Alimentarius system.184
Thus, Canada wondered whether residues inmeatarising fromthemisuse orabuse ofsubstances found
infeedadditives would bedetected under thecurrent ECregulatory scheme.
4.237 Canada alsoclaimed thattheECregulation ofthesixhormones atissue wasalsoanomalous.
Incontrast totheprohibition imposed onthethree synthetic hormones, some veterinary drugs such
asivermectin andbenzylpenicillin wereavailable over-the-counter without aprescription. Similarly,
incomparison withthestrictcontrol maintained overtheadministration ofthethreenatural hormones,
many classes ofprescription drugs might beadministered bythefarmer, insome instances without
theveterinarian evenseeing theanimals being treated.
4.238 TheEuropean Communities responded thatCanada didnotexplain thestrictconditions under
which theuseofthethree natural hormones fortherapeutic andzootechnical usewasallowed inthe
European Communities. Thethree hormones might beadministered onlybyaveterinarian, onlyby
injection orvaginal spiral (totheexclusion ofimplantation) andonlytofarmanimals which hadbeen
clearly identified. Suchtreatments mustberegistered bytheveterinarian andthese animals could not
beslaughtered formeat production before awaiting period longenough toensure thatnoresidues
were present intheirmeat. Allthese conditions ensured thatthehormones were notadministered
improperly andthatnoresidues ofhormones, other thanthose naturally produced bytheanimals
180"Determination ofVeterinary Residues inFood", supra ,note146.
181Ibid.
182"K.N. Woodward &G.Shearer, (Arlington, VA:AOAC International, 1995) "Antibiotic UseinAnimal Production
intheEuropean Union -Regulation andCurrent Methods forResidue Detection" inH.Okaetal.,eds., Chemical Analysis
forAntibiotics Used inAgriculture, note42,p.55.
183Canada indicated thatSCAN wasanECindependent advisory body which comments onthesafety offeedadditives
andhasseencertain benefits infollowing theMRL route inassuring consumer safety.
184"Maximum Residue Limits -TheImpact ofUKandECLegislation," pp.169-170.WT/DS48/R/CAN
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themselves,werepresentinthemeatdestinedforhumanconsumption.TheJECFAitselfhadrecognized
theneedforacleardistinction tobedrawn between theuseofhormones fortherapeutic orzootechnical
reasons andanimal growth promotion. when itstated:
"The Committee recognized thatcertain hormonally active substances employed asgrowth
promoters areusedinanimals forother purposes aswell. TheCommittee concluded that
residues leftaftertheuseofadrugforgrowth promotion should beconsidered separately from
residues leftaftertheuseofthatdrugforother purposes, because inthelatter case(a)the
administration ofthedrugmight bebyadifferent route and(b)adifferent withdrawal period
inconformity withgood veterinary practice might firsthavetobeestablished andobserved.
TheCommittee therefore didnotconsider residues ofhormonally active drugs usedforpurposes
other thangrowth promotion "(page 16,emphasis added).
4.239 TheEuropean Communities indicated thatthebasic provisions inEClawwhich regulated,
atEuropean Community level, theadditives infeedingstuffs wasCouncil Directive 70/524/EEC185
assubsequently amended. Ingeneral three types ofadditives might beusedbyECmember States
infeedingstuffs: antibiotics, growth promoters, coccidiostats andother medicinal substances. Theuse
ofanyofthethree types ofadditives required advanced authorization bytheECCommission after
consultation withtheStanding Committee forFeedingstuffs. There weretwotypes ofauthorizations:
(i) definitive authorization, inwhich casetheadditive wasplaced inAnnex Iofthe
Directive andmight beusedinallECmember States inaccordance withtheconditions
fixed intheauthorization; and
(ii) provisional authorization, inwhich casetheadditive wasplaced inAnnex IIofthe
Directive. Aprovisional authorization wasvalidforamaximum period offiveyears.
Among theconditions forgranting ofauthorization, particular theEuropean Communities drewattention
tothose stipulating thatthesubstance must haveafavourable effect onthecharacteristics ofthose
feedingstuffs oronlivestock production; thatatthelevelpermitted infeedingstuffs, itdidnotadversely
affect human oranimal health ortheenvironment, norharm theconsumer byaltering thecharacteristics
oflivestock products; itspresence infeedingstuffs could becontrolled; andthatatthelevelpermitted
infeedingstuffs, treatment orprevention ofanimal disease wasexcluded. Fortheissuance ofan
authorization toplace anadditive inAnnex IorII,amonograph must bedrawn up,indicating the
identification process orthecriteria fortheidentification andcharacterization oftheadditive, particularly
itscomposition anddegree ofpurity anditsphysico-chemical andbiological properties, taking account
ofscientific andtechnical knowledge. Apharmaceutical company applying fortheauthorization of
asubstance tobeusedasanadditive infeedingstuffs mustprovide theinformation andstudies prescribed
inDirective 87/153/EEC.186
4.240 TheEuropean Communities stressed thatthefactthatasubstance wasplaced inAnnex Ior
Annex IIdidnotnecessarily mean thatitwasusedautomatically inallECmember States. TheEC
member States were freetodecide which ofthose substances could beusedinfeedingstuffs intheir
territory. Theprinciple inEClawforallsubstances permitted asadditives infeedingstuffs wasthat
185ECOfficial Journal L270, 14December 1970, p.1.
186ECOfficial Journal L64,7March 1987, p.19. TheEuropean Communities added thatDirective 95/63/EC of25.10.95
(ECOfficial Journal. L265,8November 1995, p.17) laiddown theprinciples relating toofficial controls offeedingstuffs,
andDirective95/69/EC,of22December19.95(ECOfficialJournalL332,30December1995,p.15)laiddowntheconditions
forthecontrol ofestablishments producing certain sensitive additives, such asantibiotics andgrowth promoters.WT/DS48/R/CAN
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there should benoresidues ofthese substances inmeatforhuman consumption.187Theprinciple of
noresidues wasachieved withtheimposition, ifnecessary, ofappropriate withdrawal periods, aswas
thecasenotablyforgrowth-promotingadditives,coccidiostatsandothermedicinalsubstances.However,
when aparticular substance wasusedalsoasaveterinary medicinal product (i.e.substances administered
tofoodproducing animals formedical treatment), theMRLs established inthelatter casewere also
applicable when thesubstances wereusedasadditives infeedingstuffs. IntheEuropean Communities,
Council Regulation (EEC) 2377/90 of26June1990188,laiddown theMRLs forveterinary medicinal
products which were usedinfoodstuffs ofanimal origin. Theabsence ofMRLs foradditives in
feedingstuffs wasexplained bythefactthatthesubstances wereusedinverysmall quantities andwere
nearly notabsorbed, leaving practically noresidues atallinmeatdestined forhuman consumption.
However, inorder toharmonize entirely theEClegislation, theEuropean Commission would shortly
propose anamendment toDirective 70/524/EEC, which introduced MRLs alsoforadditives which
would needtobeestablished before granting anauthorization.
4.241 TheEuropean Communities indicated thatmonesin waspermitted tobeusedasanantibiotic
inbovine andascoccidiostat inpoultry, inwhich caseawithdrawal period of3dayswasrequired.
Asanionophore, itwasassumed tohaveacertain degree oftoxicity (headaches, nausea, nosebleeds,
skinrashes). Butmonesin wasnotgenotoxic normutagenic. When usedasanadditive infeedingstuffs,
noMRLs wereestablished. Thedosage ofMonesin authorized asanadditive hadbeenevaluated five
times. Itwasconcluded thatthefactthatitwasavailable asaprepared feedingstuff, thedosage permitted
andthewithdrawal periods fixed eliminated therisks ofresidues inmeat destined forhuman
consumption. Monesin wasallowed tobeusedinCanada fornutritional purposes andtheprevention
ofcoccidiosis. Benzylpenicillin wasanantibiotic substance usedmainly against gram-negative bacteria.
Itwasoneofthelongest-used antibiotics. Penicillins hadaverylowtoxicity interms ofdirect effects.
Inconnectionwiththerapeuticuse,hypersensitivityreactionswerebyfarthemostcommonlyencountered
sideeffects. Thesmall amounts ofpenicillin which might bepresent infoodproducts ofanimal origin
werenotabletosensitise humans. Forthose reasons, benzylpenicillin hadbeenincluded inAnnex I
ofRegulation 2377/90 forallfoodproducing species andanMRL of50µg/kg hadbeenestablished.
Ivermectin wasananthelmintic usedagainst various parasites. Itsscientific evaluation hadshown that
itwasneither carcinogenic normutagenic. Itwasincluded inAnnex IofRegulation 2377/90 forall
foodproducing animals. MRLs of100µg/kg ofbovine liver, 40µg/kg ofbovine fat,15µg/kg of
ovine liver, 20µg/kg ofporcine fathadbeenestablished. TheEuropean Communities added thatfor
monesin, carbadox andolaquindox, theEuropean Commission would shortly propose MRLs evenfor
feedadditives. Asfeedadditives, noveterinary control fortheirusewasrequired. Monesin wasnot
carcinogenic andavoparcin hadbeenrecently withdrawn fromuse.TheEuropean Communities noted
thatingeneral, thesystem ofsurveillance inforce intheEuropean Communities hadbeenmaintained
under thenewDirective 96/23/EC, which would enter intoforce on1July1997. However, thenew
Directive clarified andimproved theprocedures forthedetection ofresidues. Itrequired thatcontrols
should bebased primarily ontargeted andunannounced inspections, withlessemphasis onthepresent
system ofrandom sampling.
4.242 TheEuropeanCommunitiesalsoarguedthattheargumentonconsistencywhichCanadaattempted
todraw from thefactthatoestradiol-17 appeared, asasubstance forwhich noMRL wasnecessary
wasmisplaced. Asstated explicitly inECRegulation 3059/94, oestradiol-17 wasauthorized "for
therapeutic andzootechnical usesonly". Thisnatural hormone (andtheother twonatural hormones
atissue) hadtobeexamined inthecontext ofRegulation 2377/90 because otherwise itcould notbe
usedevenfortherapeutical orzootechnical purposes. NoMRL wasfixedbytheEuropean Communities
because itwasverydifficult todetect suchresidue limits onaroutine basisandwithout impeding trade.
Butitsadministration exclusively forsuchpurposes andunder theconditions prescribed inECDirective
187TheEuropean Communities noted thatthisprinciple applied alsotoimports ofmeat from third countries.
188ECOfficial Journal L224, 18August 1990, p.1.WT/DS48/R/CAN
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88/299 ensured thattherewerenoresidues leftinmeatdestined forhuman consumption. TheEuropean
Communities stressed thattreatment ofanimals fortherapeutic orzootechnical reasons wasnecessary
inexactly thesame waytreatment ofhuman beings fortherapeutic purposes bydoctors wasnecessary.
Although newsubstances fortherapeutic purposes were increasingly used, without therapeutic or
zootechnical treatment there would benomeatproduction. After suchtreatment wasperformed, the
European Communities noted thatittooksome timebefore theveterinarian discovered whether the
treatment waseffective ornot.If,depending ontheanimal andthetherapeutic orzootechnical treatment
performed, theveterinarian determined thattheanimal could notbemaintained asabreeding animal,
onlythenthepossibility ofslaughter wasconsidered. Butthismeant that,inaddition tothestrict
conditions imposed byEClawforsuchtreatment, there wasalapse oftimebetween suchtreatment
andtheslaughter. Thepercentage ofanimals receiving suchtherapeutic orzootechnical treatment
andwhich might beslaughtered didnotrepresent more than1percentoftotalbovine animals used
forhumanconsumptionintheEuropeanCommunities.Therefore,notonlythepercentagewasextremely
lowbut,inaddition, theconditions imposed forsuchtreatments andthetimewhich normally lapsed
between suchtreatments andthepossibility ofslaughtering, guaranteed thattherewould benoresidues
ofoestradiol-17 leftinmeatusedforhuman consumption. Therefore, thelevelofprotection ofthe
European Communities wasnotaffected atall.Canada appeared toconfuse, asdidDr.Arnold,
therapeutic orzootechnical usewithuseofthesehormones forgrowth promotion. Therapeutic treatment
wasperformed onlywhen theanimal wasill.Zootechnical treatment wasnormally performed only
oncetoananimal. Itwasnotperformed every year, asCanada seemed tosuggest. Animals treated
forbothofthese purposes could notbeslaughtered forhuman consumption while theywere under
treatment. Withdrawal periods were alsofixed. Ananimal which attheendofitsbreeding career
wasfattened tobeslaughtered could notbetreated fortherapeutic orzootechnical purposes. Itwas
obvious, therefore, thatunder theconditions prescribed inEClaw,there could benoresidues ofsuch
hormones inmeatwhen theanimals wereslaughtered forhuman consumption. Equally, animals treated
fortherapeutic orzootechnical reasons andmeatofsuchanimals from thirdcountries were allowed
tobeimported under guarantees which wereequivalent tothose applied fordomestic animals andmeat
from suchanimals. Therefore, theprovisions ofEClawapplied regardless ofthecountry oforigin
oftheanimals ormeat ofsuchanimals. TheEuropean Communities added thatbenzylpenicilin,
carazolol, anaesthetics andivermectin could beusedonlyunder veterinary prescription inthefollowing
ECmember States: Germany, Netherlands, Sweden, Italy, Finland andtheUnited Kingdom.
Invermectin could beusedintheUnited Kingdom without veterinary prescription butonlyasa
feedingstuff additive only. Theuseofavoparcin hadbeenprohibited inallECmember States since
theendofJanuary 1997.
4.243 Canada noted thatthere wasadegree ofriskassociated withallveterinary drugs usedfor
animal husbandry andhormones wereassafeas,orsaferthan,many other veterinary drugs commonly
usedfortherapeutic ornon-therapeutic purposes. Moreover, many ofthese veterinary drugs were
usedforanimal husbandry intheEuropean Communities, suchasanthelmintics, pesticides, andsome
antibiotics, andwere administered byproducers without aveterinary prescription.
4.244 Asoneexample, Canada noted thatmonesin wasanionophore189thathadadualrolebothas
acoccidiostat inpoultry andasagrowth promoter incattle. Toensure minimal residues inmeat, a
three-day withdrawal period wasrecommended forpoultry. Ionophores suchasmonesin werecapable
ofdisturbing biological membranes andaffecting action potentials, which presumably accounted for
theirhightoxicity. Additionally, there were highvariations inspecies toxicity. Workers involved
189Canada explained thatanionophore was"anorganic substance which binds apolar compound andactsasaniontransfer
agent tofacilitate movement ofmonovalent (i.e.,sodium andpotassium) anddivalent ions(i.e.,calcium) through cell
membranes. Thechange inelectrical charge inmembranes influences transport ofnutrients andmetabolites across thecell
membrane, buttheexact mechanism bywhich ionophores improve growth performance ingrowing ruminants isnotknown"
(D.H. Beermann, "Existing andEmergerging Strategies forEnhancing Efficiency andComposition ofMeat Animal Growth",
1995 ECScientific Conference Proceedings, p.45).WT/DS48/R/CAN
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inmonesin production orfeedcompounding hadreported adverse reactions, suchas,headaches, nausea,
nosebleeds andskinrashes.190Monesin wasadministered byproducers intheEuropean Communities
asafeedadditive. Theuseofmonesin wasgoverned bytheFeedAdditives Directive anditappeared
thatnoMRL orsafety limitwasestablished forthiscompound under theMRLs Regulation.
4.245 Withregardtonon-ionophoreantiobiotics,Canadaindicatedthatcarbadoxwasawidelyavailable
antimicrobial synthetic compound usedasagrowth promoter inpigs. Itwasbothmutagenic and
carcinogenic inanimals. Concern hadalsobeenexpressed about thesafety ofanyresidues tothe
consumer, butevidence suggested thatthese residues, when present, weredevoid ofcarcinogenic and
mutagenic activity, andanyriskwaslikely tobetotheworkers handling thedrugs.191JECFA had
evaluated carbadox in1990, butbecause ofthegenotoxic andcarcinogenic nature ofcarbadox and
some ofitsmetabolites, JECFA hadnotbeabletoestablish anADI. However, JECFA hadbeen
abletocomplete aqualitative riskassessment andconcluded thatresidues resulting from theuseof
carbadox inpigswereacceptable, provided thatMRLs werenotexceeded. JECFA hadrecommended
MRLs of0.03mg/kg inliverand0.005 mg/kg inmuscle ofpig,based onthelevels of,andexpressed
as,quinoxaline-2-carboxylic acid.192TheJECFA recommendations forcarbadox hadbeenadopted
asCodex standards.193Canada noted thatinastudy commissioned bytheEuropean Communities,
concluded in1991, itwasreported that"carbadox shows mutagenic effects inshort timetestsandin
longtermexperiments andcarcinogenic effects onrat-liver thatcould notbereproduced inexperiments
withprimates. According totoday'sstandards, aNEL [noeffect level] cannot bederived norcan
aADI".194Carbadox wasadministered byproducers intheEuropean Communities asafeedadditive.
Theuseofcarbadox wasgoverned bytheFeedAdditives Directive. Itappeared thatnoMRL orsafety
limithadbeenestablished forthiscompound under theMRLs Regulation.
4.246 Olaquindox wasanother antimicrobial feedadditive usedasagrowth promoter inpigs,which
hadbeenevaluated bytheJECFA in1994. JECFA hadconcluded that:
"...because ofthegenotoxic potential oftheparent compound andtheabsence ofspecific
toxicity studies onthemetabolites, itwasstillunable toallocate anADI. However, itnoted
thattheparent drugwasabsent inmuscle attheproposed withdrawal timeandthatthetoxicity
ofthemetabolites could bepartially evaluated onthebasis oftoxicity studies inexperimental
animals because themetabolites aresimilar tothose inthetarget species. TheCommittee
extended thetemporary acceptance ofresidues resulting from theuseofolaquindox inpigs
inaccordance withgood practice intheuseofveterinary drugs."195
190J.Weissinger, "Miscellaneous Growth Promotants," inL.M. Crawford &D.A. Franco, eds., "Animal Drugs and
Human Health" (Lancaster: Technomic Publishing Co., 1994) c.8,p.117.
191K.N. Woodward &G.Shearer, "Antibiotic UseinAnimal Production intheEuropean Union -Regulation andCurrent
Methods forResidue Detection" inH.Okaetal.,eds., "Chemical Analysis forAntibiotics Used inAgriculture" (Arlington,
VA:AOAC International, 1995) c.3,p.54.
192"Evaluation ofcertain veterinary drugresidues infood: Thirty-sixth Report oftheJointFAO/WHO Expert Committee
onFood Additives", Technical Report Series 799(Geneva: WHO, 1990), pp45-50 (hereinafter "Thirty-Sixth Report").
193"Residues ofVeterinary Drugs inFoods", supra ,note146.
194CEAS Consultants (Wye) Ltd.etal.,"The Impact onAnimal Husbandry intheEuropean Community oftheUseof
Growth Promoters: Final Report,Vol. 1:Growth Promoters inAnimal Feed" (February 1991), p.138 (hereinafter "The
Impact onAnimal Husbandry intheEuropean Community oftheUseofGrowth Promoters").
195"Evaluation ofcertain veterinary drugresidues infood: Forty-second Report oftheJointFAO/WHO Expert Committee
onFood Additives", Technical Report Series 851(Geneva: WHO, 1995) p.19.WT/DS48/R/CAN
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4.247 The1991study commissioned bytheEuropean Communities described thepublic safety aspects
ofolaquindox asfollows:
"ForOlaquindox aNELof1mg/kg hasbeendetermined. Without withdrawal timetheresidue
concentration areabove theADIvalue. Dataconcerning kinetics ofexcretion andpractical
experience indicate thatawithdrawal timeof4weeks anditsuseonlyupto4months ofage
respectively aresufficient toexclude risksforhuman health."196
Thestudy wentontoconclude:
"Considering theresidues [ofthe11antimicrobial growth promoters studied], allgrowth
permitters approved seem toshow ahighlevel ofsafety, except carbadox andolaquindox.
....Thequinoxalines andolaquindox deserve special attention concerning thesafety aspects
because theyarenearly completely absorbed inthegutandareproven tobemutagenic.
Carbadox isalsocarcinogenic. Therefore, asafety evaluation should beextended tothetarget
animal aswellastohuman beings."197
4.248 Canada observed thatolaquindox wasadministered byECproducers asafeedadditive. The
useofolaquindox wasgoverned bytheFeed Additives Directive, andnoMRL orsafety limithad
beenestablished forthiscompound under theMRLs Regulation.
4.249 Canada indicated thattherewasabodyofscientific evidence suggesting thatavoparcin presented
serious riskstohuman health, through thedevelopment ofantibiotic-resistant bacteria. Theuseof
thistypeofantibiotic atsub-therapeutic levels forgrowth promoting purposes, could result inresistant
strains ofbacteria inanimals. These resistant strains hadthepotential toenter thehuman foodchain,
causingfoodborneillness.Otherrisksincludedtransferringantibioticresistancetootherhumandisease-
causingorganisms,thusrenderingthetraditionaltherapyofhumandiseasesineffective.198TheEuropean
Communities hadalsoexamined thisissueindetail andSCAN hadrecommended further research into
196TheImpact ofAnimal Husbandry intheEuropean Community oftheUseofGrowth Promoters", supra ,note160.
197Ibid..,pp.140-141.
198J.Davies, "Bacteria ontherampage", Nature, Vol.383(19September 1996) p.219):
Avoparcin ischemically related tovancomycin (although itsname disguises thefact.). InDenmark in
1993, 22kgofvancomycin were employed inhuman therapy, while animal useconsumed 19,000 kg
ofavoparcin-inadvertentlybreakingEuropeanCommunityrules,whichstatethatnoagentsusedinhumans
andnone thatcause cross-resistance canbeusedinanimal feedadditives. Notsurprisingly, resistance
tovancomycin sharing thesame biochemical mechanisms asthatfound inhumans isolates isnowcommon
infarm animals.
Avoparcin wasalsousedinGermany, where vancomycin-resistant enterococci arenowwidespread and
canbedetected onsupermarket meat products (W.Witte, Robert Goch Inst.). Useofavoparcin isnow
prohibited inGermany andDenmark, butapowerful lobby istrying todissuade theEuropean Community
from taking general preventative action.
Other difficulties associated withtheincrease inantibiotic resistant bacteria isaninability totreathuman infectious
diseases. Asreported byS.Kingman ("Resistance aEuropean Problem, Too," Science, Vol.264(15April 1994)
pp.363-365, therising level ofantibiotic resistance isarealcause forconcern, andreports from around Europe
show thatsevere problems already exist insome countries:
Theemergence ofvancomycin-resistant Enterococci isworrisome because these bacteria arethemselves
asignificant cause ofhospital infections. Butevenmore alarming isthepossibility thatEnterococci will
spread vancomycin resistance toother genera ofbacteria. Researchers think thiswilleventually happen
because bacteria areveryadept atexchanging their antibiotic resistance genes.WT/DS48/R/CAN
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theeffects ofavoparcin, eventhough there wasevidence ofahuman health risk.199Avoparcin was
stillpermitted foruseintheEuropean Communities, withtheexception ofthose countries thathad
implemented anational ban.Thescientific community hadraised doubts about thesafety ofavoparcin,
particularly withrespect tothedetrimental effects thatthecontinued useofthisdrugcould havefor
human therapy anddevelopment ofpathogenic microbial-resistant strains thatcould appear inthefood
chain.Avoparcinwasadministeredbyproducersasafeedadditive,andcouldbeusedwithoutveterinary
supervision. Itwasgoverned bytheFeedAdditives Directive and,therefore, itappeared thatnoMRL
orsafety limithadbeenestablished forthiscompound under theMRLs Regulation.
4.250 Canadasubmittedthatbenzylpenicillinwasoneofthemostwidelyusedantibioticsinbothanimals
andhumans. Itwasprimarily usedtocontrol mastitis indairy cows andfortreating infections ofthe
urinary tract, gastrointestinal system andrespiratory tract. Benzylpenicillin wasalsoadministered as
afeedadditivetopigstocontrolstreptococcalmeningitis,andwasincludedasanadditiveinthedrinking-
water ofpoultry.200Thisdrughadbeenevaluated byJECFA in1990. TheCommittee hadconcluded
thatallergic reactions inhumans wasthedetermining factor inthesafety evaluation ofresidues of
benzylpenicillin:
"Among theadverse reactions which hadbeenreported inpeople consuming foodcontaining
benzylpenicillin residues, hypersensitivity reactions were themost common. Theoverall
prevalence ofallergy topenicillin, taking intoaccount various reports ofallergic reactions in
differentpopulationsandusingavarietyoftestprocedures,wasestimatedtobe3-10percent."201
4.251 Codex hadadopted MRLs formeatandformilk.202TheEuropean Communities hadalsoset
MRLs formilkandmeatthatwerethesame astheCodex levels.203Toensure thattheMRLs were
attained, proper dosage oftheanimal wasessential. Exceeding theMRLs could result insevere allergic
reaction in3-10percentofthepopulation. Canada noted thatalthough proper dose-level wascritical
tothesafety ofmeatormilkproducts, benzylpencillin wassoldwithout prescription andadministered
directly byfarmers incertain ECmember States.
4.252 Canada indicated thatcarazolol ,anon-specific -adrenoceptor-blocking agent, primarily used
inpigstoprevent sudden death duetostress during transportation, hadbeenreviewed byJECFA in
1994 atitsforty-third meeting. Thedrughadalsobeenusedincattle forthesame reasons andwas
usually administered totheanimals justpriortobeing loaded forshipment toaslaughter facility. The
JECFA Report noted that:
"TheCommittee [JECFA] recognized thathumans withchronic bronchitis orasthma arehighly
sensitive totheeffects ofcarazolol. Italsorecognized thatthissubgroup forms asubstantial
199Canada noted thatAgra-Europe hadreported that"...evidence hadbeenpresented toSCAN byDenmark andGermany
thattheuseofavoparcininanimalfeedcouldcausearesistancetoantibioticsinhumansbutSCANfoundthatthetwocountries'
evidence wasinsufficient proof ofalinkbetween theadditive andincreased antibiotic resistance." ("Opposition toavoparcin
inEUgrowing," (25October 1996), Agra Europe, p.E/4.)
200Thirty-Sixth Report, supra ,note158.
201Ibid.,pp.37-38.
202"Residues ofVeterinary Drugs inFoods", supra ,note147.
203R.J.Heitzman, ed.,"Agriculture -Veterinary Drug Residues -Residues infood-producing animals andtheirproducts:
Reference materials andmethods" (Luxembourg: Office forOfficial Publications oftheEuropean Communities, 1992),
pp.1-7, p.4.WT/DS48/R/CAN
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partofthegeneral population andthatadequate allowance should bemade forvariations between
individuals."204
4.253 TheJECFA hadestablished anADIandMRLs forcertain tissues. However, theproposed
standards hadnotyetpassed through theeightstepCodex process andwere, therefore, subject tochange,
based oncomments fromcountries. Nonetheless, concerning theuseofthisdrug, theJECFA Report
provided acautionary notetoregulators bystating:
"The Committee recommended thatregistration authorities should payparticular attention to
thepotential riskofresidues ofcarazolol intissue attheinjection site.Considering thepotential
risk, theCommittee concluded thattheuseofcarazolol inpigstoreduce stress during
transportation toslaughter isinconsistent withthesafeuseofveterinary drugs infoodproducing
animals "205(emphasis added).
4.254 InJune1995, theEuropean Communities hadrevised itsprovisional MRLs andhadsetfinal
MRLs permitting theuseofthisdruginpigs.206Initsanswer toaquestion fromCanada, theEuropean
Communities hadstated that,"Carazolol isusedinpigstoprevent 'mors subita 'during transport".
Canada noted thatthispractice wasprecisely whatJECFA concluded wasinconsistent withthesafe
useofveterinary drugs infood-producing animals.
4.255 Canada noted thativermectin wasanantiparasitic agent. Ithadbeenevaluated byJECFA in
1990 andagain in1993. Ivermectin wasamixture oftwohomologous compounds. While the
compound wasveryeffective indealing withparasites, themode ofaction inparasites hadremained
elusive, andthemechanisms ofthetoxic action ofivermectin inmammalian species hadnotbeen
elucidated.207Thetypical signs ofacute toxicity ofivermectin hadbeenattributed toitseffects on
thecentral nervous system. Codex hadadopted theJECFA recommended ADIs andMRLs forcattle,
sheep andpigs208forivermectin asCodex standards.209Ivermectin wasapproved foruseintheEuropean
Communities, andanMRL inthetarget tissues ofliverandfathadbeensetforthebovine andporcine
species. Itwasavailable forusebyproducers without aveterinarian prescription insome ECmember
States.
4.256 Canada submitted thatinveterinary medicine, apesticide wasacompound which wasactive
against parasites thatliveontheskinofanimals orwhich spend partoftheirlivesintheanimal 'sbody
(e.g.,warble flylarvae). Intheirlarval stage, theseparasitic organisms known asectoparasites, might
migrate through thetissue ofthehost,orburrow intoandliveinthesuperficial skinlayers. Tocounter
ectoparasites, therefore, itwasimportant tohaveacompound thatcould destroy theparasites atevery
stage oftheirlifecycle, including thelarval stage. Arange ofapplication modes forthepesticides
wereavailabletotreattheanimals,suchasdips,sprays,dusts,feedadditives,orsubcutaneousinjections.
Duetoenvironmental concerns, theorganophosphourous compounds hadreplaced most ofthe
organochloride compounds foruseaspesticides. Unfortunately, theorganophosphourous compounds
204"Evaluation ofCertain Veterinary Drug Residues inFood: Forty-third report oftheJointFAO/WHO Expert Committee
onFood Additives" (Geneva: WHO) Section 3,"Comments onresidues ofspecific veterinary drugs," 3.1"-Adrenoceptor-
blocking agent." p.6.
205Ibid.,p.8.
206Regulation 1442/95/EC.
207Thirty-sixth Report, supra ,note158.
208Ibid.,p.30.
209"Residues ofVeterinary Drugs inFoods", supra ,note147.WT/DS48/R/CAN
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weremoretoxictomanthantheorganochlorides, although theywererapidly metabolized andexcreted.
Compounds suchasdiazionon were usedintheEuropean Communities.210
4.257 Canada indicated thatbecause theuseofagricultural production aids,suchasveterinary drugs,
presentedarisk,albeitminuscule,totheconsumer,theUnitedStatesDepartmentofAgriculture(USDA)
haddeveloped amethod todetermine therelative riskofvarious agricultural production aidssuchas
veterinarydrugs,naturallyoccurringtoxins,andpesticides.TheUSDA'sCompoundEvaluationsSystem
("CES"), developed in1983, hadguided anumber ofcountries inthedevelopment oftheirresidue
monitoring programmes. Thisallowed fortesting tobetargeted atthose compounds thatweremore
likely topresent ahealth risktotheconsumer.
4.258 Thelikelihood ofahealth hazard ofcompounds which leftresidues infoodwasrated Ato
DorZ.Thehighest health hazard compounds were scored Aandthelowest received aD.Those
compounds forwhich insufficient information wasavailable toconduct atoxicologic orpharmacologic
evaluation, received arating ofZ.Eachcompound wasalsoassigned arating toevaluate theprobability
ofexposure totheconsumer. Thecategories ranged from 1,meaning ahighprobability ofexposure,
to4,which wasnegligible probability ofexposure. Category Zdesignated asubstance withinsufficient
information available toestimate theprobability ofexposure tohumans.211TheCEScould thusbe
usedtorankcompounds based ontheirrelative risk. Thecompounds presenting thehighest riskto
human health would score A1,andthecompounds withthelowest risktohuman health would bethose
compounds withascore ofD4.Compounds ofunknown hazard orexposure riskwould receive a
Zrating.
4.259 Thenatural hormones were notranked bytheCESsystem astheydidnotleave detectable
residues infoodanddidnotpresent anyrisktohuman health. Canada presented theCESranking
ofvarious veterinary drugs212,andclaimed thatitillustrated thatthenatural andsynthetic hormones
were safer thanseveral veterinary drugs commonly usedforanimal production intheEuropean
Communities.
Trenbolone C-4
Zeranol C-2
MGA B-4
Carbadox A-3
Olaquindox (Notpermitted foruseinCanada)
Avoparcin (Notpermitted foruseinCanada)
Monesin B-3
Carazolol (Notpermitted foruseinCanada)
Penicillin A-2
Ivermectin B-1
4.260 TheEuropean Communities noted thatthebasic provisions inEClawwhich regulated the
additives infeedingstuffs wasCouncil Directive 70/524/EEC213,assubsequently amended several times.
210Regulation 1442/95/EC establishes aMRL fordiazinon.
211"CompoundEvaluationandAnalyticalCapability:NationalResidueProgramPlan1993"(Washington:U.S.Department
ofAgriculture, Food Safety andInspection Service), pp.1.3-1.7.
212"Compound Evaluation andResidue Information 1994" (Washington: U.S. Department ofAgriculture, Food Safety
andInspection Service), pp.2.3-2.5.
213ECOfficial Journal L270, 14December 1970, p.1.WT/DS48/R/CAN
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There were ingeneral three types ofadditives which might beusedbytheECmember States in
feedingstuffs: antibiotics, growth promoters, coccidiostats andother medicinal substances. Before any
ofthethree types ofadditives might beused, anauthorization hadtobegranted bytheCommission
afterconsulting theStanding Committee forFeedingstuffs. There were twotypes ofauthorization:
(i) definitive authorization, inwhich casetheadditive wasplaced inAnnex Iofthedirective
andmight beusedinalltheECmember States inaccordance withtheconditions fixed
intheauthorization; and
(ii) provisional authorization, inwhich casetheadditive wasplaced inAnnex IIofthe
Directive. Aprovisional authorization wasvalidforamaximum period offiveyears.
4.261 hemain conditions forincluding asubstance inAnnex Irequired that:
(i) thesubstance musthaveafavourable effect onthecharacteristics ofthose feedingstuffs
oronlivestock production;
(ii) atthelevelpermitted infeedingstuffs, itdidnotadversely affect human oranimal health
ortheenvironment, norharm theconsumer byaltering thecharacteristics oflivestock
products;
(iii) itspresence infeedingstuffs could becontrolled;
(iv) atthelevelpermitted infeedingstuffs, treatment orprevention ofanimal disease was
excluded.214
4.262 Fortheissuance ofanauthorization toplace anadditive inAnnex IorII,amonograph must
bedrawn up,indicating theidentification process orthecriteria fortheidentification andcharacterization
oftheadditive, particularly itscomposition anddegree ofpurity anditsphysico-chemical andbiological
properties, taking account ofscientific andtechnical knowledge (Article 8:1). Thefactthatasubstance
wasplaced inAnnex IorAnnex IIdidnotnecessarily mean thatitwasusedautomatically inallEC
member States; ECmember States werefreetodecide which ofthose substances touseinfeedingstuffs
intheirterritory.
4.263 Theprinciple inEClawforallsubstances permitted asadditives infeedingstuffs wasthatthere
shouldbenoresiduesofthesesubstancesinmeatforhumanconsumption.215Theprincipleofnoresidues
wasachieved withtheimposition, ifnecessary, ofappropriate withdrawal periods, aswasthecase
notably forgrowth-promoting additives, coccidiostats andothermedicinal substances. However, when
aparticular substance wasusedalsoasveterinary medicinal product (i.e.substances administered to
foodproducing animals formedical treatment), theMRLs established inthelatter casewere also
applicable when thesubstances wereusedalsoasadditives infeedingstuffs. Council Regulation (EEC)
2377/90 of26June1990216,laiddown theMRLs forveterinary medicinal products which wereused
infoodstuffs ofanimal origin. Theabsence ofMRLs foradditives infeedingstuffs wasexplained by
thefactthatthesubstances were usedinsuchsmall quantities andwere littleabsorbed sothatthey
leftpractically noresidues inmeatdestined forhuman consumption. However, inorder toharmonize
entirely thelegislation within theEuropean Communities, theEuropean Commission would shortly
214TheEuropean Communities indicated thatthiscondition didnotapply tococcidiostats andother medicinal substances.
215TheEuropean Communities indicated thatthisprinciple applied alsotoimports ofmeat from third countries.
216ECOfficial Journal L224, 18August 1990, p.1.WT/DS48/R/CAN
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propose anamendment toDirective 70/524/EEC, which would require MRLs alsoforadditives before
granting anauthorization.
4.264 TheEuropean Communities stressed thatonlytwogrowth promoting substances could beused:
carbadox andolaquindox (Annex I(J)ofDirective 70/524/EEC).217However, certain ECmember
States hadasked theEuropean Commission toreview theauthorizations ofcarbadox andolaquindox,
andtheCommission hadagreed, before theCouncil ofMinisters on26February 1996, andon
17December 1996 toreview both ofthese substances shortly after avoparcin, ronidazole and
dimetridazole (possibly inthecourse of1997). Carbadox, olaquindox andavoparcin hadalready been
examined andreviewed recently intheSCAN committee andtheauthorization foravoparcin hadalready
beenwithdrawn.
4.265 TheEuropean Communities added thatatECleveltherewere10antibiotics which wereallowed
tobeusedasadditivesinfeedingstuffsintheECmemberStatesandwhichmightalsofunctionasgrowth-
promoters because theystabilized thefloraandreduced thepathogenic micro-organisms intheanimals
andinduced ahigher feedefficiency andgrowth rate. Most, ifnotall,ofthese substances werealso
allowed tobeusedinCanada fornutritional uses(growth promotion). Canada allowed moresubstances
thantheEuropean Communities tobeusedasantibiotics andascoccidiostats infeedingstuffs (only
21coccidiostats were permitted intheEuropean Communities).
4.266 TheEuropean Communities explained thatmonesin waspermitted tobeusedasanantibiotic
inbovines andascoccidiostat inpoultry, inwhich caseawithdrawal period of3dayswasrequired.
Asanionophore, itwasassumed tohaveacertain degree oftoxicity (headaches, nausea, nosebleeds,
skinrashes). Butmonesin wasnotgenotoxic normutagenic. When usedasanadditive infeedingstuffs,
noMRLs wereestablished, asexplained above (Directive 70/524). Thedosage ofmonesin authorized
asanadditive hadbeen evaluated fivetimes. Itwasconcluded thatitsavailability asaprepared
feedingstuff, thedosage permitted andthewithdrawal periods fixed eliminated therisksofresidues
inmeatdestined forhuman consumption. Monesin wasallowed tobeusedinCanada fornutritional
purposes andtheprevention ofcoccidiosis. Avoparcin wascurrently allowed tobeusedasanantibiotic
infeedingstuffs. Itwasnotcarcinogenic, butitwasthought toposerisksbecause ofthedevelopment
ofantibiotic-resistant bacteria which could possibly transfer tohumans. Since itwasusedasa
feedingstuff only, there noMRL wasfixed. TheCommission wasintheprocess ofwithdrawing its
authorization, inaccordance withtheopinion oftheSCAN. Benzylpenicillin wasanantibiotic substance
usedmainly against gram-negative bacteria. Itwasoneofthelongest-used antibiotics. Penicillins
hadaverylowtoxicity interms ofdirect effects. Inconnection withtherapeutic use,hypersensitivity
reactions werebyfarthemostcommonly encountered sideeffects. Thesmall amounts ofpenicillin
which maybepresent infoodproducts ofanimal origin werenotabletosensitize humans. Forthese
reasons, benzylpenicillin wasincluded inAnnex IofRegulation 2377/90 forallfoodproducing species.
AnMRL of50µg/kg hadbeenestablished. Ivermectin wasananthelmintic usedagainst various
parasites. Itsscientific evaluation hadshown thatitwasneither carcinogenic normutagenic. Itwas
included inAnnex IofRegulation 2377/90 forallfoodproducing animals. MRLs of100µg/kg of
bovine liver, 40µg/kg ofbovine fat,15µg/kg ofovine liver, 20µg/kg ofporcine fathadbeen
217TheEuropean Communities indicated thataprovisional comparison withthesituation inCanada, asregards substances
usedasadditives infeedingstuffs forgrowth -promotion, would appear toindicate thatmore additives forgrowth promotion
were usedinCanada. Thus, although Canada didnotallow theuseofolaquindox, itdidallow (inaddition tothehormones
atissue)theuseofcarbadox,chlorotetracyclinehydrochloride,oxytetracyclinehydrochloride,3-nitro-4-hydroxyphenylarsonic
acid,arsanilicacid,bambermycins,bacitracin,methylenedisalicylate,lincomycin,procainepenicillin,etc.Apartfromcarbadox,
olaquindox (andbacitracin zincforswine only), theother substances were notallowed tobeusedasgrowth-promoting feed
additives intheEuropean Communities. Itshould alsobenoted thatthe1991 JECFA report oncarbadox andolaquindox
concluded thatresidues resulting from theuseofcarbadox inpigswere acceptable provided thattherecommended MRLs
werenotexceeded (aswasthecaseintheEuropean Communities), andresidues fromtheuseofolaquindox infood-producing
animals under conditions ofgood practice intheuseofveterinary drugs were temporarily acceptable.WT/DS48/R/CAN
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established. Although formonesin, carbadox, olaquindox andavoparcin, there werenoMRLs, the
European Commission would soonpropose MRLs forfeedadditives. Asfeedadditives, noveterinary
control fortheirusewasrequired.
4.267 With regard tobenzylpenicillin andivermectin, theEuropean Communities argued thata
prescription byaveterinarian wasrequired inorder toavoid riskstoconsumers offoodstuffs obtained
fromthetreated animals. Ifinsome ECmember States noprescription waseffectively required, this
wasnotinconformity withtheprovisions ofthisDirective. TheEuropean Commission hadalready
requested therelevant information fromalltheECmember States. Forthemoment notallhadreplied,
butthesituation ofthose which hadreplied showed thatinGermany andDenmark neither ofthese
twosubstances could beobtained without prescription. Aprescription wasalsorequired inFrance.
IntheNetherlands, benzylpenicillin wassubject toveterinarian prescription. TheCommission had
information which showed thatinIreland onlybenzylpenicillin wasavailable without prescription,
andonlytofarmers organisations carrying outaspecial programme fortheprevention ofmastitis in
cows. Thisprogramme wascarried outunder veterinary supervision andapplied toalimited number
ofanimals.218
4.268 TheEuropean Communities explained thatthemeasures which ECmember States mustput
inplace toensure thattheMRLs forbenzylpenicillin andivermectin were notexceeded. Council
Directive 86/469/EEC harmonised controls onresidues inliveanimals (bovines, pigs, sheep, goats
andhorses) andfresh meat, bothoftheEuropean Communities andthirdcountries which exported
meattotheEuropean Communities. Itsupplemented Directive 85/358/EEC which setouttherules
onthedetection andmonitoring ofsubstances having ahormonal orthyrostatic action. Theaimwas
toexamine animals, theirtissues andbiological material andfresh meatforthepresence ofresidues
ofsubstanceshavingapharmacologicalactionorofconversionproductsandothersubstancestransmitted
tomeatwhich were likely tobedangerous tohuman health. TheECmember States were allowed
tocontrol forresidues ofanysubstance which might poseadanger tohuman oranimal health.
4.269 Thesubstances andresidues tobechecked weredefined inAnnex IofDirective 86/469/EEC.
Thesubstances were divided intodifferent groups orsub-groups according totheir chemical or
pharmacological action. Theminimum sampling levels andfrequency werealsodefined inAnnex II
oftheDirective. Thesamples hadtobetaken fromliveanimals atfarmlevelorattheslaughterhouse
before slaughtering, andfromcarcasses atslaughterhouse level. Amonitoring plantaking intoaccount
thespecific situation ofeachECmember Stateandsetting outthenational measures tobetaken had
tobesubmitted every yeartotheEuropean Commission (Articles 3and4).TheCommission examined
theplans presented bytheECmember States inorder todetermine wether theyconformed tothe
provisions laiddown inDirective 86/469/EEC. These plans were updated eachyearinthelightof
experience. Forexample, onthebasis ofpositive results recorded during aprevious year, search for
newsubstances, improvements gained inlaboratory techniques, etc.Official samples wereexamined
inapproved laboratories forresidues (Article 8).National Reference Laboratories coordinated standards
andmethods ofanalysis foreachgroup ofresidues, asdefined intheAnnex IoftheDirective. Four
ECReference Laboratories were designated tohelptheCommission andtheNational Reference
Laboratories (NRL) toimprove theharmonization ofthemethods ofanalysis andthequality ofthe
workofeachNRL. Incaseanofficial sample revealed thepresence ofresidues ofprohibited substances,
orquantities ofauthorized substances exceeding ECorstricter national MRLs, thecompetent authorities
oftheECmember States mustundertake investigations atthefarmoforigin without delay, andlaunch
aninquiry intotheorigin ofthesubstances concerned, asnecessary, atthelevels ofmanufacture,
handling, storage, transport, administration, distribution orsale. Positive animals (forprohibited
218Thistypeofclinical trials were provided forinArticle 14ofregulation 2377/90 of26June 1990 (ECOfficial Journal.
L224,18August 1990, p.1), oncondition thatfoodstuffs obtained from livestock participating insuchtrials notcontain
residues which posed ahazard tohuman health.WT/DS48/R/CAN
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substances) werebanned from human andanimal consumption andadditional monitoring tookplace
onthefarms ofsuchanimals. Inthecaseofauthorized substances, meat inwhich thepresence of
residuesinexcessoftheMRLswasconfirmedwasexcludedfromhumanconsumption.Allthenecessary
administrative andpenal sanctions hadtobetaken bycompetent authorities toensure thatthese
requirements were strictly observed.
4.270 Asregarded imports fromthirdcountries, theadmission orretention onthelistofthirdcountries
which wereauthorized toexport animals ormeatofanimals forhuman consumption totheEuropean
Communities wassubject tothesubmission bythethirdcountry concerned ofanannual plandetailing
oftheguarantees forthechecking ofresidues. Theeffect oftheseguarantees mustbeatleastequivalent
tothatresulting fromtheguarantees provided forinDirective 86/469/EEC. Thethirdcountry plans
wereapproved bytheEuropean Commission inaccordance withtheopinion oftheStanding Veterinary
Committee. Theannual plans of25thirdcountries hadcurrently beenapproved, andthese countries
exportedmeatwhichrespectedtheMRL requirementsoftheEuropeanCommunities,wheretheyexisted.
Inaddition, those countries which allowed theuseofhormones forgrowth promotion fortheirdomestic
production hadallconcluded arrangements withtheEuropean Communities toensure thatthemeat
exported totheEuropean Communities wasproduced without hormones forgrowth promotion.
4.271 Ingeneral, thesystem ofsurveillance nowinforce hasbeen maintained under thenew
Directive96/23/EC,whichwouldenterintoforceon1July1997.However,thenewDirectiveclarified
andimproved theprocedures forthedetection ofresidues. Itrequired thatcontrols should bebased
primarily ontargeted andunannounced inspections, withlessemphasis onthepresent system ofrandom
sampling. Under thenewDirective, themonitoring plans hadtobeextended topoultry meat, fish,
milk, andsome other products (rabbit andgame meat, honey eggs). More flexibility wasgiven to
sampling plans, according tothespecific problems ofeachECmember State. ThenewDirective would
improve harmonisation ofmethods ofanalysis, forbothroutine andreference methods. Itwould extend
thecompetence ofthefourECReference Laboratories toproducts other thanmeat, andtoother types
ofresidues notyetcovered bythecurrent residues Directives. Directive 96/23/EC would establish
clearly theresponsibilities ofeachoperator andwould strengthen thesanctions against thefarmers
andtheoperators (veterinarians, pharmacists, slaughterhouses, etc.)incaseofdetection ofresidues
ofprohibited substances orresidues ofauthorized butillegally usedsubstances. Serious financial
andadministrative sanctions would beimposed incaseoffraud, without prejudice topossible penal
sanctions taken bythecompetent authorities oftheECmember States. ThenewDirective would also
improve transparency oncontrol results since itrequired theirannual publication andaswellasthe
publication ofaEuropean Commission report totheCouncil andtotheEuropean Parliament concerning
thesituation ofresidues control intheEuropean Communities.
4.272 Canada recalled thatparagraph 5ofAnnex Adefined appropriate level ofsanitary and
phytosanitary protection as"[t]he levelofprotection deemed appropriate bytheMember establishing
asanitary orphytosanitary measure toprotect human, animal orplantlifeorhealth within itsterritory"
andobserved thatArticle 5.5oftheSPSAgreement limited thischoice ofanappropriate level of
protection byrequiring thatarbitrary andunjustifiable distinctions inthelevelofprotection considered
appropriate indifferent situations must notresult indiscrimination, oradisguised restriction on
international trade.219TheEuropean Communities maintained thatitwashighly riskaverse, andthat
itsprohibition ontheuseofhormones forgrowth promotion, including thesixhormones atissue, was
necessary toachieve itshighlevelofsanitary protection. However, asCanada hadjustdemonstrated,
ECmeasures governing theuseofother growth promoters andveterinary drugs revealed thata
significantly lower levelofprotection wasconsidered appropriate fortheriskstohuman health posed
bythose substances. Thesixhormones inquestion wereassafeas,orsaferthan, growth promoters
219J.J.Barcelo, "Product Standards toProtect theLocal Environment -theGATT andtheUruguay Round Sanitary and
Phytosanitary Agreement", (1994) 27Cornell International LawJournal,. Vol.755, pp.765-66.WT/DS48/R/CAN
Page101
commonly usedintheEuropean Communities. Moreover, theyweredemonstrably saferthanveterinary
drugs thatwere commonly usedintheEuropean Communities.
4.273 Canada submitted thatantimicrobial growth promoters distributed asfeedadditives posed no
lessrisktohuman health thanthesixhormones atissue. Three antimicrobial growth promoters
authorized foruseintheEuropean Communities wereparticularly noteworthy: carbadox wasknown
tobebothmutagenic andcarcinogenic; olaquindox wasmutagenic; andtherewasscientific evidence
indicating thattheuseofavoparcin asafeedadditive presented aserious risktohuman health because
itmight leadtothedevelopment ofvancomycin-resistant strains ofbacteria. YettheECmeasures
governing theuseoffeedadditives weresubstantially lessrestrictive thanthecomplete banontheuse
ofthesixgrowth promoting hormones forgrowth promotion purposes. Growth promoters and
coccidiostats regulated under theECFeed Additives Directives could beadministered byproducers
without thesupervision ofveterinarians, andwerenotsubject totheauthorization procedures andMRL
requirements setoutintheMRLs Regulation ortheresidues monitoring requirements established under
Residues Directives. Canada argued thatgiven thatthese substances posed nolessariskthanthat
posed bythesixgrowth promoting hormones, itfollowed thatthese lessrestrictive measures could
notpossibly attain thesame levelofprotection thatpurportedly laybehind theprohibition ontheuse
ofthesixhormones forgrowth promotion purposes. Thiswould bethecaseevenifthese substances
weresubject toMRL requirements andresidue monitoring requirements. Itwasapparent thattheEC
level ofsanitary protection forgrowth promoting hormones wassignificantly higher thanthelevel
forantimicrobial growth promoters.
4.274 Furthermore, Canada claimed thatmany veterinary drugs usedfortherapeutic purposes and
governed bytheVeterinary Medicines Directives posed demonstrably greater riskstohuman health
when compared tothesixhormones.220While veterinary drugs were subject totheauthorization
procedures andMRL requirements oftheMRLs Regulation andtheresidues monitoring requirements
ofResidues Directives, under thelawsofECmember States some ofthese substances, suchas
benzylpenicillinandivermectin,mightbeadministeredbyfarmerswithoutprescriptionorthesupervision
ofaveterinarian. Farmers might evenadminister prescribed veterinary drugs without theveterinarian
evenseeing theanimals being treated. Canada claimed thatthese lessrestrictive measures could not
possibly attain thesame levelofprotection thatpurportedly laybehind theprohibition ontheuseof
thesixhormones forgrowth promotion purposes. Itwasagain apparent thattheEClevelofsanitary
protection forgrowth promotion hormones wassignificantly higher thanthelevelforother veterinary
drugs commonly usedintheEuropean Communities.
4.275 Canada argued thatthese marked distinctions inlevels ofprotection were arbitrary and
unjustifiable,andresultedindiscriminationandadisguisedrestrictiononinternationaltrade.221Canadian
220Canada noted that, forexample, incontrast toveterinary drugs with fixed MRLs under Annex IofDirective
2377/90/EEC, orprovisional MRLs under Annex III,oestradiol-17 wasplaced inAnnex IIasasubstance forwhich no
MRL wasnecessary (Regulation 3059/94/EC). Carazolol, ontheother hand, poses asignificant risktohumans withchronic
bronchitis orasthma andhasbeen assigned aMRL.
221J.J.Barcelo, supra ,note179, atpp.765-66 provided auseful example:
Aparty must "avoid arbitrary orunjustifiable distinctions inthelevels itconsiders tobeappropriate in
different situations, ifsuchdistinctions result indiscrimination oradisguised restriction oninternational
trade." Themeaning ofthislanguage isnotimmediately apparent, butonitsfaceitcould provide aground
foramore searching scrutiny ofaparty'sS&Pprovisions thananyoftheother three requirements thus
fardiscussed. Weshould note, however, thatthe"arbitrary distinctions" language istiedtotheproviso
"ifsuchdistinctions result indiscrimination oradisguised restriction oninternational trade." Thatproviso
helps toclarify thekindofcaseenvisioned. Agood example isthewellknown German Beer casein
EUlawdecided bytheEuropean Court ofJustice in1987.
(continued...)WT/DS48/R/CAN
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beeffrom cattle treated withthesixhormones forgrowth promotion purposes posed nogreater risk
toECconsumers thanECbeeftreated withanti-microbial growth promoters orother veterinary drugs.
Theprohibition onimports ofbeeffrom cattle treated withthesixhormones forgrowth promotion
discriminated against Canadian beefimports, andconstituted anunwarranted restriction ofthistrade
intheguise ofasanitary measure. Canada claimed, therefore, thattheECmeasures were contrary
toArticle 5.5.
4.276 TheEuropean Communities responded thatthere wasnothing inthetextofthecontested
measures, thelegislative history orinanyother document tosuggest thatthepurpose forwhich the
measures wereadopted wastoprotect ECproduction ofmeatfromforeign competition. Itwasincorrect
toconclude thatbecause theEuropean Communities didnot,inthiscase, follow thevoluntary MRLs
suggested byCodex onthefivehormones andbecause itapplied different levels ofprotection fortotally
different substances which posed entirely different types ofrisks tohuman andanimal health, the
European Communities mustbeconsidered tohaveviolated itsobligations under theSPSAgreement.
Canada hadfailed toestablish that,inthefaceoftheoverwhelming scientific evidence thattheuse
ofhormones foranimal growth promotion waspotentially verydangerous topublic andanimal health,
there were other typeofmeasures which, while significantly lessrestrictive oftrade, were capable
ofensuring thatthelevelofprotection which theEuropean Communities hadchosen inthiscase(no
residue ofhormones inanimals andmeat) could beeffectively achieved. Conversely, theEuropean
Communities hadgonethrough thatexercise in1984 andrecently inApril 1996andhaddecided that
theprohibition onuseofthesehormones inanimal growth promotion wastheonlymeasure reasonably
available andlessrestrictive oftrade. TheEuropean Communities argued thatCanada compared things
which werenotcomparable, because thepremises onwhich theywerebased weredifferent, andthat
Canada confused thenotions of"risk","appropriate levelofprotection", and"measures applied to
achieve thatlevelofprotection".
4.277 TheEuropean Communities insisted thatunder theSPSAgreement, eachMember hadtheright
tosetitslevelofsanitary protection where andhowitchose. Theonly(minimal) disciplines imposed
bytheSPSAgreement inrespect ofthelevelofprotection wereinArticles 5.4and5.5,asfollows:
221(...continued)
IntheGerman Beer case, Germany allowed beertobesoldinGermany andlabelled "bier" onlyifit
wasmade from malted barley, hops, yeast, andwater. Noadditives atallwere allowed. Most German
beerhasbeen made inthismanner since thesixteenth century. Beer inother EUcountries, however,
isfrequentlymadefromriceandothercereals.Inthecaseofthesebeers,additivesareneededfortechnical
reasons toproduce thebeer. TheGerman ruletherefore prevented much ofthebeermade inother EU
countries from being imported andsoldinGermany as"bier". Germany triedtojustify theruleinpart
ontheground thatGermans consume large quantities ofbeerandthattheadditives ingeneral would pose
ahuman health risk. TheEuropean Court ofJustice rejected thisargument, however, foroneverystriking
reason: forallbeverages, other thanbeer, German lawspecifically allowed some oftheveryadditives
thatwere banned completely inbeer. Thus, thearbitrariness ofthese distinctions appeared toconvince
theEuropean Communities thattheGerman regulation wasessentially aform ofdisguised protectionism
designed toprotect German beerproducers from non-German competitors.
Suppose, forexample, thatthetoxicity ofpesticides YandZareindistinguishable. Suppose further that
theUnited States adopts arulecalling forzeropesticide Zresidue onapples. TheU.S. provision might
runintotrouble if,forexample, pesticide Zwere traditionally usedinCanada, pesticide YintheUnited
States, andthezeropesticide ruleapplied onlytopesticide Z.
Admittedly, judgments could differ about theapplication ofthis"arbitrary distinctions" standard. But
initsdefense, howelsecould onedealwithasituation suchasthatpresented bytheGerman Beercase,
apparently acaseofdisguised protectionism? There isariskofaninappropriate panel decision under
thestandard. Without it,however, there would bealoophole through which very large amounts of
disguised protection could bedriven.WT/DS48/R/CAN
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(i) Members should takeintoaccount theobjective ofminimizing negative trade effects
(Article 5.4)(emphasis added).
(ii) With theobjective ofachieving consistency intheapplication oftheconcept of
appropriate levelofprotection, Members shallavoid arbitrary orunjustified distinctions
inthelevels theyconsider tobeappropriate indifferent situations, ifsuchdistinctions
result indiscrimination oradisguised restriction oninternational trade (Article 5.5)
(emphasis added).
4.278 TheEuropean Communities argued thatbecause there might often bearange ofsanitary or
phytosanitary measures available toachieve thesame levelofprotection, themeasures employed by
various Members might differ evenwhere theyweredesigned toachieve thesame levelofprotection.
Differences inthetypeofmeasures applied might, however, restrict trade without providing any
additional protection tohuman, animal orplantlifeorhealth. TheEuropean Communities contended
thatitwasforthispurpose thatArticle 5.5contained thenotion ofconsistency. Article 5.5didnot
require Members toachieve consistency between thelevel ofprotection which theychoose against
different hazards tohuman, animal andplant lifeandhealth, butonlyrequired consistency interms
ofavoiding arbitrary orunjustifiable distinctions inapplying thechosen levelofprotection, andthen
onlyifsuchdistinctions resulted indiscrimination oradisguised restriction ontrade. Itcould notbe
interpreted asrequiring consistency insetting ordeciding thelevelofprotection. Thisinterpretation
wasconsistent withthepreamble oftheSPSAgreement, which stated thattheharmonization ofSPS
measures didnotrequire Members tochange theirappropriate levelofprotection.
4.279 TheEuropean Communities noted thatthetextofArticle 5.5didnotgofurther indefining
consistency. Consistency wasnotharmony withpastperformance, particularly inthecontext ofthe
SPSAgreement, where newdiseases might beemerging andnewtechnologies emerging todealwith
olddiseases. Thedefinition ofconsistency which bestfittheintention oftheSPSAgreement was
"constant adherence tothesame principles ofthought oraction".222Thisconstant adherence hadto
beapplied tothesame substances, which posed thesame typeofriskunder same conditions ofuse.
TheEuropean Communities argued thatinthecontext oftheSPSAgreement, thefactual andlegal
situation currently existing inMembers regarding regulation ofdangerous substances should alsobe
taken intoaccount. Consistency wasadynamic process evolving withtechnology, newriskassessment
andtheconfines ofregulatory policies which required years toreview existing authorizations of
dangerous substances. Toinferlackofconsistency on1January 1995 from thecomplex situation
thatexisted before theentry intoforce oftheAgreement wastodisregard theletter ofArticle 5.5,
toignore thepractical situation inalmost allMembers andtothreaten thecredibility oftheSPS
Agreement.
4.280 TheEuropean Communities argued thatitwasbecause ofthisreality thatthenegotiators had
adopted thereasonable approach ofdeveloping guidelines "tofurther practical implementation ofthis
provision" envisaged inArticle 5.5.IntheEuropean Communities 'view, thisinitselfwasindicative
oftheabsence ofaconsensus ontheimplications oftheprovision atthetimetheAgreement was
negotiated andsigned. Therefore, thetextofparagraph 5clarified thattheconcept ofconsistency
wasonlyanobjective tobeachieved intheapplication oftheappropriate level ofsanitary or
phytosanitary protection against riskstohuman, animal orplantlifeorhealth. Thiscould alsobeseen
from thedrafting history ofthisprovision. On13June1995, theWTO Secretariat hadcirculated a
note223onthedrafting history oftheprovision onconsistency. Thelastparagraph ofthenotestated
that:
222Oxford English Dictionary.
223G/SPS/W/16.WT/DS48/R/CAN
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"...thepurpose oftheprovision istoensure thatgovernment decisions astowhatlevels of
riskareacceptable invarious situations arenottaken insuch amanner astoresult in
discrimination ordisguised restrictions ontrade. Ithasbeenagreed thatthemechanism for
ensuring thatgovernments avoid arbitrary orunjustifiable distinctions inthelevels ofriskthey
accept istorequire governments tobeconsistent intheirriskmanagement decisions."
Thesame notealsoclarified thatduring thenegotiations, concern hadbeenexpressed thatwhatwere
considered asacceptable levels ofriskwithregard toanimal orplant health could notnecessarily be
considered aspolitically acceptable levels ofriskinmatters regarding human health, orvice-versa.
Itwasalsostated thatconsistency might bedesirable andachievable among decisions regarding animal
health,orevenbetweenplantandanimalhealthissues,however,anacross-the-boardconsistencybetween
decisions regarding human, animal andplant health riskswasnotacceptable.
4.281 TheEuropean Communities observed thatthedrafting history demonstrated, therefore, that
thenegotiators oftheSPSAgreement hadnever hadinmind asituation similar totheonepresented
byCanada, where measures applied equally toimported anddomestic products werecompared with
other measures applied tototally different substances which posed different types ofrisks. Discussions
intheSPSCommittee hadfocused onhowtoensure consistency, oncomparisons between human health
ononesideandanimal andplanthealth ontheother, andonvoluntary risks, buthad,sofar,yielded
noconcrete guidelines. Theonlynotion thathadalegalmeaning wastheprohibition ofarbitrary and
unjustifiable distinctions, iftheyresulted indiscrimination ordisguised restriction. Itshould therefore
benoted thatabsolute consistency wasnotwhatwasimplied inArticle 5.5,butrather thatitwasa
step-by-step process, anobjective which wastobeachieved byrespecting thelegalobligation setout
inArticle 5.5ofavoiding arbitrary andunjustifiable distinctions.
4.282 TheEuropean Communities noted thatCanada compared measures adopted withregard to
hormones withmeasures adopted withregard toother substances, andtherisksposed byhormones
andthese other substances, respectively. TheEuropean Communities claimed thatArticle 5.5dealt
withneither ofthese twonotions -neither withmeasures, norwithrisks. Article 5.5established an
obligation toavoid "arbitrary andunjustifiable distinctions inthelevels [ofsanitary orphytosanitary
protection against riskstohuman lifeorhealth, ortoanimal andplant lifeorhealth] itconsiders to
beappropriate indifferent situations, ifsuchdistinctions result ...".Inotherwords, Article 5.5imposed
anobligation nottoarbitrarily distinguish between levels ofprotection. Nodirect comparison of
measures ,norofriskswasenvisaged. Furthermore, theprovision didnotprohibit overtly alltypes
ofdistinctions inthelevels ofprotection, onlythose distinctions which werearbitrary andunjustifiable,
andwhich resulted indiscrimination ordisguised restriction. Thesecond could notbeassumed to
beaconsequence ofthefirst; itwasaseparate qualification. Canada, therefore, wasrequired toprove
thatthelevels ofprotection were different, thatthedistinction wasarbitrary andunjustifiable, and
thatitresulted indiscrimination oradisguised restriction oninternational trade.
4.283 TheEuropeanCommunitiesfurtherarguedthattherequirementinArticle5.5toavoid"arbitrary
orunjustifiable distinctions inthelevels" considered tobeappropriate, using "levels" intheplural,
indicated thattheSPSAgreement accepted thataMember might havemorethanonelevelofprotection,
applicable todifferent situations. Article 5.5didnotrequire Members toapply thesame level of
protection against possible adverse health effects fromallpests, diseases andcontaminants, asCanada
suggested.Thiswouldbeabsurdbecausethedegreeofseverityofadversehealtheffectsvariedaccording
tothepestordisease andbecause Members could notbeexpected toprovide thesame degree of
protection toplants which theyapplied tohumans. Moreover, itwould beequally unreasonable to
interpret Article 5.5,asCanada did,torequire Members tochoose thesamelevelofprotection against
residues ofallveterinary drugs. Notallveterinary drugs hadthesame adverse effects onconsumers
through residues infood, andMembers were atliberty tochoose different levels ofprotection for
different residues, aslongasthelevelwasconsistent indifferent situations forthesame residue. This
wastheessence oftheruling bytheEuropean Court ofJustice intheGerman Beercase,citedbyCanadaWT/DS48/R/CAN
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(footnote toparagraph 4.275, footnote 221)anditwasthecasewiththeECrules onhormones and
other veterinary drugs.
4.284 TheEuropean Communities admitted thatCanada might bejustified toclaim thattheEuropean
Communities 'level ofprotection against aparticular adverse health effect, e.g.cancer, should be
consistent evenwhere thateffect wascaused bydifferent substances. TheEuropean Communities had
chosen itsmeasures inthelightofthespecific circumstances inwhich eachsubstance wasusedinorder
toachieve itsappropriate levelofprotection. Acomparison ofthehormones withfeedadditives acting
asgrowth promoters, suchascarbadox andolaquindox, hadtotakeintoaccount thefollowing elements:
(i) carbadox andolaquindox were nothormones, although theybothacted asgrowth
promoters;
(ii) thehormones atissue, when administered forgrowth promotion, speeded updirectly
thefeed-weight conversion rateoftheanimals, whereas carbadox andolaquindox acted
asgrowth promoters onlyindirectly bycombating thedevelopment ofbacteria and
byaiding theintestinal floraofpiglets;
(iii) carbadox andolaquindox were commercially available onlyasprepared feedstuffs,
notasinjections orimplants norascombinations;
(iv) theywere allowed tobeadministered onlytopiglets, totheexclusion ofanyother
animal;
(v) there werenocommercially alternative products forcarbadox andolaquindox which
possessed notonlythegrowth promotion aspect butalsothemedicinal effects ofthese
twosubstances;
(vi) therewerenoincentives norpotential formisuse sincethesetwosubstances could exert
growth promotion onlyinpiglets, notinother animals; and
(vii) allsubstances were saidtobegenotoxic andcarcinogenic.
4.285 Onthebasisoftheseelements, theEuropean Communities argued thatcarbadox andolaquindox
were different substances from thehormones atissue, although theyposed thesame typeofriskto
human oranimal health. Theconditions imposed bytheEuropean Communities guaranteed, however,
thatthere were noresidues ofcarbadox andolaquindox inmeat destined forhuman consumption.
Therefore, thelevelofprotection, "noresidues inhuman food", wasthesame withregard tothese
twosubstances andthehormones.224TheEuropean Communities recalled thatwhen ECmember States
made checks forthese substances, theywerechecking toensure thatthere werenoresidues. There
wasnotolerance levelthatwaspermitted fortheresidues ofthese twosubstances inmeatforhuman
consumption. Butthefactthatithadchosen toapply thislevelofprotection bymeasures different
from those itapplied togrowth hormones wasirrelevant. TheEuropean Communities choose its
measures inthelightofthespecific circumstances inwhich eachsubstance wasused.
4.286 Insummary, theEuropean Communities noted thattheSPSAgreement allowed Members to
choose theirappropriate levelofprotection bytheirchosen political process andonlyrequired this
choice tobe"consistent" inrespect ofthesame hazard indifferent situations. TheSPSAgreement
didnotrequire Members tousethesame measures tocontrol thesame hazard indifferent situations.
224TheEuropean Communities noted that,asithadindicated, itwasgoing toreview these twosubstances shortly and
already intheprocess ofwithdrawing theauthorization foravoparcin, theother substance mentioned byCanada. Thisshowed
thattheEuropean Communities hadalready achieved averyhighdegree ofconsistency intheir legislation.WT/DS48/R/CAN
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Onthecontrary, itrequired measures tobe"tailored", bymeans ofriskassessment, toensure that
theywere appropriate tothecircumstances. Tocompare measures taken withregard tohormones
withmeasures taken withregard toother substances wasnotrelevant norsignificant forthepurposes
ofdetermining theexistence ofabreach ofArticle 5.5.More restrictive measures werenotnecessarily
equivalent toahigher levelofprotection, andmore important still,"lessrestrictive" measures were
notatallindicative ofalower level ofprotection. Measures were taken toachieve theappropriate
levelofprotection. Itwas,therefore, useless tocompare measures which were applied todifferent
products, different risks andindifferent circumstances. Moreover, thecomparison of"risks" was
alsonotcorrect. Levels ofprotection weretobecompared, andmeasures taken toachieve suchlevels
weretobebased onriskassessment, asappropriate tothecircumstances. TheEClevelofprotection
wasthesameintheexamples invoked: noresidues ofthehormones atissueinmeatdestined forhuman
consumption. Theriskagainst which itsmeasures aimed toprotect theECconsumers wasalsothe
same: carcinogenicity. TheEuropean Communities used different measures asaresult ofrisk
assessments appropriate tothecircumstances, which tookintoaccount thefactors outlined inArticle 5.2.
4.287 TheEuropean Communities argued thatalthough Canada hadclaimed that"itisapparent that
theEClevel ofprotection forgrowth-promoting hormones issignificantly higher than" forother
substances, Canada hadnotdemonstrated, firstofall,theexistence ofdifferent levels ofprotection
andsecond, thattheothertwoconditions werealsomet.Finally, theEuropean Communities concluded
thatCanada hadstated thattherewereabout 10,000 to15,000 authorized veterinary medicinal products
intheEuropean Communities. Yet,Canada 'sclaim oflackofconsistency intheEuropean Communities
waslimited tofivesubstances. Thisshowed thatthere wasindeed already averyhighdegree of
consistency intheEClegislation.
4.288 Canada didnotdisagree withtheECstatement that"Article 5.5imposes anobligation not
toarbitrarily distinguish between levels ofprotection. Nodirect comparisons ofmeasures ,norofrisks
isprovided here." Canada argued, however, thatitwasnotcorrect tostatethat"...Itis,therefore,
useless tocompare measures alone which areapplied todifferent products, different risksandindifferent
circumstances". Canada submitted thatthePanel wasnotprevented from looking attheevidence it
hadpresented toinferthattheEuropean Communities applied distinctly different levels ofprotection,
andthatintheabsence ofanyprecise articulation bytheEuropean Communities astowhatitslevel
ofprotection was,despite repeated requests byCanada andother WTO Members inconsultations,
acomplaining party andthePanel were leftwithnoother recourse.
4.289 Canada claimed that,contrary totheECarguments, Article 5.5addressed precisely theissue
ofconsistency inthesetting ordeciding oftheappropriate levelofprotection. TheECinterpretation
wasnotconsistent withthetextofArticle 5.5.Nowhere didArticle 5.5speak of"...avoiding arbitrary
orunjustifiable distinctions inapplying thechosen levelofprotection ....". Rather, itspoke to"...the
objective ofachieving consistency intheapplication oftheconcept ofappropriate level ofsanitary
orphytosanitary protection ....". Moreover, inCanada 'sview, theECinterpretation wasalso
inconsistent withthenegotiating history oftheSPSAgreement. AsthenotebytheSecretariat on
consistency inriskmanagement decisions made clear, Article 5.5wasdrafted withtheintention of
ensuring some consistency inthedecisions ofgovernments when setting ordeciding appropriate levels
ofprotection :
"Asthefollowing review ofthedrafting history oftheSPSAgreement makes clear, itwas
agreed ataveryearlystageinthenegotiations thatsanitary andphytosanitary measures should
notbeapplied inanarbitrary orunjustifiably discriminatory manner. Itwasalsoagreed that
sanitary andphytosanitary measures should primarily bebased onriskassessment andanalysis,
andsubsequently thateach government wasresponsible forthedetermination ofwhat it
considered tobeitsacceptable levelofrisk(appropriate level ofsanitary orphytosanitary
protection). From thisitfollowed thattoensure thatsuchgovernmental decisions didnotresultWT/DS48/R/CAN
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inarbitrary orunjustifiable discrimination intheapplication ofsanitary orphytosanitary
measures, there mustbesome consistency inthedecisions taken225(emphasis added).
Once theconcept ofgovernments deciding whatwasanacceptable levelofriskonthebasis
ofananalysis oftheactual risksinvolved wasadopted asabasic element oftheemerging SPS
Agreement, itwasrecognized thatdisciplines wereneeded toensure thatthisrighttotakea
sovereign decision notbeusedtocircumvent theobligations ofnon-arbitrariness orunjustifiable
discrimination intheidentification andmeasurement ofrisks, itwasnoted thatthere wasstill
ample scope forgovernments tosuccumb topolitical pressures toprotect certain domestic
industries from foreign competition through theirdecisions regarding acceptable levels of
risk/sanitary andphytosanitary protection "226(emphasis added).
4.290 Canada contended thatthescope ofthephrase "different situations" should beinterpreted in
thecontext oftheobjective ofArticle 5.5,setoutintheopening clause: "With theobjective of
achieving consistency intheapplication oftheconcept ofappropriate levelofsanitary orphytosanitary
protection against riskstohuman lifeorhealth, ortoanimal andplantlifeorhealth ...". Asthenote
oftheSecretariat explained:
"The nextconcern wasthatwhatwereconsidered asacceptable levels ofriskwithregard to
animal orplanthealth could notnecessarily beconsidered as(politically) acceptable levels of
riskinmatters regarding human health, orvice-versa. Thatis,consistency might bedesirable
andachievable among decisions regarding animal health, orevenbetween plant andanimal
health issues, however anacross-the-board consistency between decisions regarding human,
animal andplant health riskswasnotacceptable."227
4.291 Thus, inthepresent case, itwasclearthattheappropriate levelofprotection underlying the
ECmeasures mustbecompared forconsistency onlyamong decisions regarding theappropriate level
ofprotection forother sanitary measures protecting human health .Inthatregard, Canada noted that
alltheexamples ithadraised identified thepotential foradverse health effects inhumans arising from
veterinary drugresidues inmeatandother animal products. Moreover, theECinterpretation would
limit"different situations" to"thesameresidue" or,atmost, "different substances" causing "aparticular
adverse health effect". TheEuropean Communities offered nosupport forthisnarrow interpretation,
asidefromtheNotecitedabove, which onlyspoke oflimiting consistency inthiscasetohuman health.
4.292 Canada submitted thatthephrase "different situations" captured allthedifferent sanitary risks
posed tohuman health contemplated bytheSPSAgreement ,i.e.,those arising fromdifferent sources,
orcausing different adverse health effects. Thus, within theterms oftheSPSAgreement ,anddrawing
upon theapplicable paragraphs inthedefinition ofasanitary measure setinAnnex A,(i.e.,
paragraphs 1(b)and(c)),"different situations" would capture risksposed tohuman health "...arising
fromadditives, contaminants, toxins ordisease-causing organisms infood, beverages orfeedstuffs,"
aswellasrisks"...arising fromdiseases carried byanimals, plants orproducts thereof, orfromthe
entry, establishment orspread ofpests".228Inthepresent case, "different situations" would capture
theriskstohuman health posed by,interalia,contaminants suchasveterinary drugs residues, pesticides
andheavymetals,bytoxinssuchasbotulinumtoxin,fumonesinandaflatoxin-B1,andbydisease-causing
organisms suchassalmonella, E.coliandcampylobacter.
225"Consistency inRiskManagement Decisions", G/SPS/W/16, p.2,para. 4.
226Ibid.,p.3,para. 7.
227"Consistency inRiskManagement Decisions", G/SPS/W/16, p.4,para. 11.
228Definition ofSPSmeasure: SPSAgreement Annex A,para. 1.WT/DS48/R/CAN
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4.293 Inthealternative, ifthePanel didnotaccept thisinterpretation, Canada submitted that,atthe
veryleast, thescope of"different situations" encompassed similar risksandsimilar products.229In
thisregard, theexamples citedbyCanada described avariety ofveterinary drugs which wereroutinely
usedbyECfarmers inanimal production andwhich leftresidues inmeatandmilk. Thus, theproducts
were similar. Theadverse health effect thatwasthedetermining factor inthesafety evaluation of
eachresidue might bedifferent: forexample, JECFA hadconcluded thatallergic reactions inhumans
wasthedetermining factor inthesafety evaluation ofbenzylpenicillin. However, thesedifferent adverse
effects might benolesssevere thancancer: forexample, allergic reactions topenicillin hadcaused
anaphylactic deaths.230Thus, theriskswere similar. Itwasapparent thatwhatever theEClevelof
sanitary protection wasforthesixhormones atissue, itmustbesignificantly higher thanitslevelfor
antimicrobial growth promoters, inparticular carbadox andolaquindox, andforanumber ofother
veterinary drugs. These distinctions were arbitrary andunjustifiable.
4.294 Canada argued thatthephrase "each Member shallavoid arbitrary orunjustifiable distinctions
inthelevels itconsiders tobeappropriate" indicated thatonlysome distinctions weretobeavoided,
i.e.,those thatwere arbitrary orunjustifiable. Itfollowed thatother distinctions were permissible,
i.e.,those thatwerejustifiable. Canada submitted thatdistinctions might bejustified when theseverity
oftheadverse health effects posed bydissimilar risksweresignificantly different. Thus, ifonerisk
involved acute, anaphylactic shock thatmayleadtodeath astheadverse health effect, andanother
riskinvolved amild, transient stomach upset, ahigher levelofprotection fortheformer when compared
tothelatter could bejustified. However, suchadistinction would bearbitrary andunjustifiable if
theriskscompared involved adverse health effects ofcomparable severity.
4.295 Canada further submitted thatthere wasnoreason tosubject consumers tohigher riskfrom
theresidues ofveterinary drugs usedfortherapeutic purposes, versus those usedforother purposes,
suchasgrowth promotion: adistinction intheappropriate levels ofprotection would notbejustified.
Canada suggested thatthedistinction between using veterinary drugs fortherapeutic purposes, versus
using themforother purposes, suchaszootechnical orgrowth promotion purposes, wasinmany ways
afalsedichotomy. Using veterinary drugs fortherapeutic purposes notonlybenefited ananimal by
improvingtheanimal'swelfare,italsobenefitedthefarmerbecausetheanimalbecamemoreproductive.
Ultimately, whether afarmer would useaveterinary drugtocureadisease inafoodproducing animal
wasstillaneconomic question: ifthecosts outweighed thebenefits, theanimal probably would not
betreated.
4.296 Canada noted thatingesting sufficient quantities oftheresidues ofveterinary drugs commonly
usedbyfarmers intheEuropean Communities could cause severe adverse health effects, i.e.,could
result indeath. Carbadox wasagenotoxic carcinogen inanimals, aswasoneofitsmetabolites. Allergic
reactions tobenzylpenicillin residues inhypersensitive members ofthepopulation could cause
anaphylaxis, leading todeath. Persons suffering frompulmonary obstructive diseases, suchaschronic
asthma, were extremely sensitive tonon-selective B-adrenoceptor antagonists, suchascarazolol; a
sufficient doseofcarazolol could cause severe bronchial constriction andasphixiation, again leading
229Canada noted thatitwasinteresting tonotethatthedraft guidelines prepared bytheChairman oftheSPSCommittee
suggested thatataminimum thiswasthescope of"different situations" contemplated byArticle 5.5. Guideline 7stated:
"Aproposed decision onanappropriate levelofprotection should becompared withprevious decisions taken with
regard tohuman health, animal health, orplant health, atleastforsimilar risksorsimilar products. Anysubstantive
differences intheproposed/accepted levelofprotection should bedulyjustified inaccordance withtheprovisions
oftheAgreement." Draft -"Draft Guidelines toFurther thePractical Implementation ofArticle 5.5", Note.by
theChairman, 16September 1996.
230W.G. Huber (1986), "Allergenicity ofAntibacterial Drug Residues," inA.G. Rico, ed.,Drug Residues inAnimals
(Orlando: Academic Press), pp.46-49.WT/DS48/R/CAN
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todeath. Organo-phosphate pesticides werepowerful neuro-toxins, andsomewerealsocarcinogenic.231
Thus, Canada argued, theseverity ofthepotential adverse health effects ofthese substances was
comparable to,orgreater than, thatofthesixhormones atissue.
4.297 Canada submitted thatthephrase "ifsuchdistinctions result indiscrimination oradisguised
restriction oninternational trade" wenttotheheart ofthepurpose ofArticle 5(5). AstheSecretariat
Note onthenegotiating history stated:
...itwasnotedthattherewasstillamplescopeforgovernmentstosuccumbtopoliticalpressures
toprotect certain domestic industries fromforeign competition through theirdecisions regarding
acceptable levels ofrisk/sanitary andphytosanitary protection.232
Canada argued thatadisguised restriction could befound when additional factors notrelevant tothe
protection ofhealth ledtotheintroduction ofmeasures thatwere more restrictive thannecessary to
meetlegitimate sanitary concerns, albeit presented intheguise ofasanitary measure. Toparaphrase
thenoteoftheSecretariat, without thisdiscipline, there would beample scope forgovernments to
succumb topolitical pressures toprotect orachieve certain domestic interests, without regard totheir
impactoninternationaltrade,throughtheirdecisionsregardingacceptablelevelsofsanitaryprotection.233
4.298 Canada submitted that,ontheevidence andarguments presented initssubmissions, thePanel
could inferdistinct appropriate levels ofprotection forthesixhormones atissueandforotherveterinary
drugs commonly usedbyfarmers intheEuropean Communities. Itwasapparent that,whatever the
EClevel ofsanitary protection forthesixhormones atissue, itmust behigher thanitslevel for
antimicrobial growth promoters, inparticular carbadox andolaquindox, andforanumber ofother
veterinary drugs citedinCanada 'ssubmissions. Canada claimed thatthese distinctions werearbitrary
andunjustifiable. There wasnoobjective principle thatcould justify them, since theseverity ofthe
potential adverse effects ofthese other substances werecomparable, ifnotgreater. These distinctions
resulted indiscrimination against Canadian beefimports, andconstituted anunwarranted restriction
inthistrade intheguise ofasanitary measure. Inthisregard, theECsubmissions were telling:
"Ofthe31countries which areauthorized toexport meattotheEC,only6allow fortheuse
ofsomeorallofthehormones atissuehereasgrowth promoters (Argentina, Australia, Canada,
NewZealand, South Africa andtheUSA). These sixcountries arethemain meatproducing
andexporting countries "234(emphasis added).
4.299 Canada concluded thattheECmeasures constituted adisguised restriction because additional
factors notrelevant totheprotection ofhealth ledtotheintroduction ofmeasures thatwere more
restrictive thannecessary tomeet thelegitimate sanitary concerns. TheEuropean Communities
succumbed topolitical pressures toprotect orachieve certain domestic interests, without regard to
their impact oninternational trade, andtheeffects onexports ofCanadian beeftotheEuropean
Communities hadbeendevastating.
4.300 TheEuropean Communities considered thatthephrase "different situations" could onlyapply
tosamesubstances (orresidues fromthesamesubstances), iftheyleadtodifferent levels ofprotection.
TheEuropean Communities indicated thatthatitparticipated actively intheSPSCommittee work on
231Dr.McLean, answer toPanel question 11,para. 6.131.
232WTO Secretariat, "Consistency inRiskManagement Decisions", G/SPS/W/16, p.3,para. 7.
233Ibid.,p.3,para. 7.
234European Communities 'firstwritten submission, para. 91.WT/DS48/R/CAN
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consistency guidelines. Butguidelines hadnotyetbeenestablished, andtheEuropean Communities
submitted thatCanada made arguments andadvanced interpretations which hadnotyetbeenagreed.
TheEuropean Communities stressed thattheguidelines invoked byCanada werenomore thandraft
guidelines, prepared bytheChairman oftheSPSCommittee aftertheentry intoforce oftheSPS
Agreement, inhisattempt todevelop theguidelines mentioned inArticle 5.5.ThetextofArticle 5.5
wasnotintended tomean andcould notbeapplied inthewayinterpreted byCanada. IntheECview,
theinterpretation ofArticle 5:5advanced byCanada inthiscasewascontrary tothecustomary principles
oftreaty interpretation, because itdisregarded thetext,object andpurpose ofthatprovision anddid
notmake sense from thesystematic point ofviewaslongastheSPSCommittee hadnotagreed on
theguidelines foritspractical implementation.
4.301 TheEuropean Communities argued thatArticle 5.5provided forachieving consistency inthe
levels ofprotection in"different situations". Thesituations referred toweremainly tradeandmarketing
situations. Theobjective wasthataMember should apply thesame level ofprotection against the
same health hazard whether thehazard arose from domestic production orfrom imports and,inthe
caseofimports, thesamelevelofprotection should beapplied inrespect ofthesame hazard inimports
from different countries. Thewords "different situations" could alsocover thedifferent elements
mentioned inArticle 5.2,i.e.process andproduction methods, inspection, sampling, testing, diseases,
ecological andenvironmental conditions, etc.Thisdidnotmean thatthemeasures adopted toachieve
thelevelofprotection would always bethesame. Forexample, theEuropean Communities hadadopted
ahighlevelofprotection against foot-and-mouth disease, having eradicated itfrom itsterritory by
aslaughter policy. However, itimported susceptible animals andtheirproducts frommany countries,
some ofwhich stillhadthedisease. Therefore, inrespect ofinfected countries itimposed conditions
onimports which weredesigned tokeepthedisease outofitsterritory. TheEuropean Communities
didnotimpose thesame measures ondomestic production oronimports from other thirdcountries
which didnothavethedisease. Thus, itslevel ofprotection wasconsistent butitsmeasures were
different: theywere tailored totheriskinvolved. TheEuropean Communities claimed thatithad
thesame policy withregard tohormones. Itdidnotallow theadministration ofthese hormones in
meatinitsterritory andmeatimported fromavariety ofthirdcountries, some ofwhich allowed the
useofthese hormones forgrowth promotion, others ofwhich didnot.Forthose which didnot,no
special conditions were imposed onimports. Forthose which allowed such use, the
EuropeanCommunitiesimposedmeasuresonimportswhichweredesignedtomeetitslevelofprotection.
4.302 "Different situations" could notmean thatthesamelevelofprotection mustbeapplied tosimilar
healthhazards,whatevertheirnatureorseverity,comingfromsimilarsubstances.Thehazardsassociated
withdifferent diseases andcontaminants weredifferent intheirnature andseverity, andaffected different
species. Itwould clearly beunreasonable iftheSPSAgreement were tobeinterpreted asrequiring
Members toadopt thesame levelofprotection against, forexample, ringworm incattle andcholera
inhumans. Itwas,however, reasonable tohavethesame level ofprotection against eachofthese
diseases regardless ofitsorigin, i.e.whether itarose inside theterritory oftheMember orasaresult
ofimportation. Thesame applied tocontaminants. Hormones hadtheirownparticular effects; some
ofthese effects might besimilar to,orthesame as,other drugs suchascarbadox, butsome were
different andwereunique tohormones. TheEClevelofprotection waschosen forprotection against
alltheundesirable effects ofhormones, notonlycancer which wasthemostimportant one. Inany
case, itslevel ofprotection against carcinogenic substances, whatever theirsource, wasconsistent.
Article 5.5clearly stated that"arbitrary orunjustifiable" distinctions weretobeavoided iftheyresulted
indiscrimination oradisguised restriction ontrade. Iftheydidnotresult indiscrimination oradisguised
restriction ontradetheywerenotprohibited bytheSPSAgreement. Inthepresent dispute, however,
thisprovision wasirrelevant since theEuropean Communities didnotmake anydistinction initslevel
ofprotection between different situations. Itslevelofprotection wasthesameirrespective ofthesource
ofhormones. Ofcourse, itsmeasures toenforce thislevel ofprotection differed according tothe
circumstances oftherisk,which inturndiffered according towhether hormones wereallowed tobeWT/DS48/R/CAN
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usedfreely forgrowth promotion, orwhether theywereallowed tobeusedonlyunder strictveterinary
control fortherapeutic purposes.
4.303 TheEuropean Communities argued thatitsmeasures resulted innodiscrimination. TheEC
levelofprotection wasdesigned toprotect against particular hazards, notagainst classes ofpotential
sources ofanyhazard, suchasall"diseases", or,asinthisquestion, all"veterinary drugs". Notall
veterinary drugs hadthepotential tocause adverse health effects inconsumers, justasnotallhuman
drugs carried thesamerisksforconsumers. Forexample, morphine andaspirin werebothpain-killers
but,because ofthedifferent degrees ofriskassociated withthem, theformer wasonlyavailable for
administration bydoctors while thelatter wasavailable overthecounter, without prescription. Of
course theEuropean Communities didnothavealevelofprotection against those hormones produced
naturally inthebody, anymore thanitdidagainst anyother natural component ofthebody. Asfar
asother veterinary drugs wereconcerned, theEuropean Communities hadthesamelevelofprotection
against other carcinogenic drugs asitdidforhormones. Itsmeasures weredesigned toachieve this
although, given thedifferent circumstances under which thedifferent drugs were used, theymight
bedifferent fromthemeasures usedforhormones. Nevertheless, theyweredesigned togivethesame
levelofprotection. TheEuropean Communities didnot,therefore, make anydistinctions, arbitrary,
unjustifiable orother, initslevelofprotection against thesamehazard arising fromthesamesubstances
indifferent situations.
4.304 TheEuropean Communities argued thatCanada hadnotshown thatthere werearbitrary and
unjustifiable distinctions inthelevels ofprotection theEuropean Communities wasapplying forthese
hormones andtheother twosubstances. Thelevels forthese twodifferent groups ofsubstances were
thesame, notarbitrary. They werealsojustified, because therewasplenty ofscientific evidence which
showedthatthesehormonesandtheirmetaboliteswerecarcinogenicevenatphysiologicallevels,whereas
inthecaseofcarbadox themetabolites which could befound inthemuscle werenotcarcinogenic and
inthecaseofolaquindox thestudies ofJECFA were stillinconclusive. ThefactthattheEuropean
Communities didnotagree withtheconclusions oftheJECFA report onhormones butfollowed the
JECFA report inthecaseoftheother twosubstances, didnotnecessarily mean lackofconsistency.
Thedifferent situations inthetwocasejustified thedifference intheapproach, bothontechnical and
scientific grounds, without however affecting theEClevels ofprotection.
4.305 Canada hadnotshown thatthedistinctions resulted indiscrimination oradisguised restriction
oninternational trade. Canada didnotevendiscuss thiscondition indepth, buthadsimply made an
automatic assumption thatitwasfulfilled inthiscase. TheECmeasure didnotdiscriminate against
Canada, because Canada could export hormone-free meattotheEuropean Communities likeanyother
country. Theproduction ofmeattreated withhormones wasnotaspecific characteristic ofCanada 's
production, norwastheproduction ofhormone-free meatapeculiar characteristic ofmeatproduction
intheEuropean Communities. Therefore, there wasnodiscrimination ineffect. Inorder toshow
discrimination anddisguised restriction Canada hadargued thattheMembers which were suffering
from theECmeasure werethesixprincipal producers ofmeatintheworld. Thistypeofargument
enlarged theelements ofcomparison inanunacceptable way. Buteventhisclass ofcountries was
nottreated differently among themselves, ontheonehand, andtheother meat producing countries
(e.g.Argentina) ontheother, because anyoneofthemcould export hormone-free meattotheEuropean
Communities under exactly thesame conditions asthose applied toallother thirdcountries aswell
aswithin theEuropean Communities. Inaddition, Canada hadnotshown whatother measure, apart
from lifting theprohibition, theEuropean Communities could takeinthiscasewhich would notbe
disguised andwould achieve itsappropriate levelofprotection. Canada hadcertainly notdemonstrated
thatithadbeentheintention oftheEuropean Communities when adopting itslevelofprotection was
toputinplace adisguised restriction oninternational trade. IfCanada wasaffected, itwasbecause
ofitsdecision nottocomply withthepossibilities offered bytheECmeasures. Forinstance, the
European Communities would import pigmeatfromCanada treated withcarbadox orolaquindox under
thesame conditions allowed intheEuropean Communities.WT/DS48/R/CAN
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(l) Article 5.6oftheSPSAgreement
4.306 Canada noted thatArticle 5.6prescribed howaMember mustensure thatanysanitary measure
wasapplied onlytotheextent necessary toprotect human, animal orplant lifeorhealth andstressed
thatineffect, Article 5.6setouthowaMember wastomeetthisbasic requirement ofArticle 2.2:
"Without prejudice toparagraph 2ofArticle 3,when establishing ormaintaining sanitary or
phytosanitary measures toachieve theappropriate levelofsanitary orphytosanitary protection,
Members shallensure thatsuchmeasures arenotmoretrade-restrictive thanrequired toachieve
theirappropriate levelofsanitary orphytosanitary protection, taking intoaccount technical
andeconomic feasibility."
Afootnote totheparagraph provided that:
"Forthepurposes ofparagraph 6ofArticle 5,ameasure isnotmore trade-restrictive than
required unless there isanother measure, reasonably available taking intoaccount technical
andeconomic feasibility, thatachieves theappropriate level ofsanitary andphytosanitary
protection andissignificantly lessrestrictive totrade."
4.307 InCanada 'sview, itwasclear thatunder theFeed Additives Directives, theEuropean
Communities maintained regulatory control overantimicrobial growth promoters thatwassignificantly
lessrestrictive totrade thanthecomplete banontheuseforgrowth promotion ofthesixhormones
atissue. Moreover, theEuropean Communities itselfasserted thatitsappropriate levelofprotection
wasthesame forcarbadox asitwasforthese hormones. Ifthiswasthecase, thenitwasclear that
theprohibition onbeeffromcattle treated withthesixhormones atissuewasfarmore trade-restrictive
thanrequired. Therisks posed bycarbadox were greater thanthose posed bythesixhormones at
issue andthere wasnotechnical oreconomic reason whyasimilar scheme could notreasonably be
extended tothesesixhormones. Canada 'sposition wasthattheECmeasures weremoretraderestrictive
thannecessary toachieve thelevelofsanitary protection achieved bytheFeedAdditives Directives,
andtherefore theECmeasures were contrary toArticle 5.6.
4.308 TheEuropean Communities noted thatArticle 5.6required measures tobe"notmore trade-
restrictive thanrequired toachieve theappropriate levelofprotection" andargued thatthere wasno
obligation tochange thelevelofprotection. Thefootnote toArticle 5.6explained thatameasure was
notmoretrade-restrictivethanrequiredunlesstherewasanothermeasurewhichwaslesstrade-restrictive
andstillmetthechosen level ofprotection, taking intoaccount technical andeconomic feasibility.
Inthese circumstances, itwasuptoacomplaining Member todemonstrate thattherewassuchanother
measure.
4.309 Noting thatlabelling might seem tobeareasonable alternative totheprohibition applied by
theEuropean Communities ontheuseofthese hormones forgrowth promotion, the
European Communities argued thatthestarting pointtotakeintoaccount wasthattheresidues ofthese
hormones posed veryserious riskstohuman andanimal health, ofwhich cancer wasthemostimportant.
Itmight bethattheprobability ofthisriskarising wasrelatively small, asDr.Lucier, oneoftheexperts
advising thePanel hadargued, buttheSPSAgreement didnotrequire aquantification oftheriskand
thelevelofsanitary protection aMember determined tobeappropriate could bezerorisk. Either there
wasariskornot;ifthere wasone,nomatter howsmall, aMember wasallowed nottoaccept that
risk.Some partsofthepopulation could notcopewithlabelling (could notread, could notunderstand,
etc.), sothecompetent authorities hadtoassume theirresponsibilities tothepublic. Labelling, therefore,
wasinherently contradictory withalevelofnoriskfrom residues ofthese hormones.
4.310 TheEuropean Communities observed thatlabelling might function inMembers which hada
lower levelofprotection thantheEuropean Communities inthiscase. There might indeed beconsumersWT/DS48/R/CAN
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inCanada whowould prefer hormone-free meat. Inthatsituation, itwasconceivable tothinkoflabelling
meat as"hormone-free" meat. Conversely, labelling could notwork where thelevel ofprotection
washigher. Imports ofmeatlabelled treated withhormones, ifallowed, would undermine thelevel
ofprotection intheEuropean Communities asECfarmers would alsoliketoproduce meatwiththe
hormones inorder toavoid unfair competition from imported cheap labelled meat. Butthismight
expose theentire population intheEuropean Communities toaninvoluntary risk,because aperson
could notverify whether meatserved inarestaurant washormone-free. Unlike other pre-packed and
labelled foodproducts, where theoriginal producer wasindicated andcould betraced backinorder
toimpose sanctions incaseofviolations, labelling wasnoteasily applicable tomeatsoldforhuman
consumption.
4.311 TheEuropean Communities claimed thatinvoluntary exposure toarisk,nomatter howsmall,
could notbelabelled. Thisconcept wasincluded inArticle 5.5,where reference wasmade tothe
"exceptional character ofhuman health riskstowhich people voluntarily expose themselves". Labelling
ofapacket ofcigarettes wasnotthesame aslabelling meat. Smoking andeating werenotthesame
typeofactivity andthevoluntary/involuntary nature oftheexposure totheriskwasveryimportant.
When theEuropean Communities imported meatfromcountries where theuseofgrowth promoting
hormones wasauthorized, itrelied firstontheguarantees given bythegovernmental authorities of
thatMember thattheimported meatwashormone-free meat. Inaddition, theEuropean Communities
carried outanumber ofsystematic andrandom controls andchecks inorder toverify whether the
assurances given bythestateauthorities wererespected. Withlabelling, therewould benosuchstate
assurances, aslabelling would beaninitiative ofprivate farmers. Thenumber ofcontrols andchecks
would therefore havetoincrease substantially without anycertainty thatthere would benoviolations
ofthelevelofprotection.
4.312 Incontrast, theEuropean Communities noted thatthelabelling ofmeatasBSE-free innoway
affected thelevelofprotection aMember hadadopted against BSE. Itmade nodifference whether
there wereincidences ofBSErecorded inthecountry ornot,because inbothsituations theobjective
wastoeradicate ortoavoid thepotential source oftheriskfromBSEinfected meat. Labelling inthis
typeofsituations, therefore, reinforced thelevelofprotection aMember hadalready putinplace and
wasnotlikely toundermine it.Conversely, thesituation oflabelling meattreated ornottreated with
hormones wascompletely different.
3. Agreement onTechnical Barriers toTrade
4.313 Canada submitted thefollowing submissions alternatively, incasethePanel decided thatthe
matters atissue werenotgoverned bytheSPSAgreement. Canada argued thattheTBTAgreement
didnotapply tosanitary measures andrecalled thatArticle 1.5oftheTBTAgreement readasfollows:
"TheprovisionsofthisAgreementdonotapplytosanitaryandphytosanitarymeasuresasdefined
inAnnex AoftheAgreement ontheApplication ofSanitary andPhytosanitary Measures."
IftheECmeasures were notcharacterized as"sanitary andphytosanitary measures", thentheyfell
within thedisciplines oftheTBTAgreement as"technical regulations".235
4.314 Canada noted thattheTBTAgreement setouttwobasic obligations withrespect totechnical
regulations, inArticles 2.1and2.2.Neither ofthese obligations hadbeenmetbytheECmeasures
atissue. Canada hadargued thattheECmeasures hadcreated obstacles toCanadian tradebystopping
theimportation bytheEuropean Communities ofCanadian beefproduced withgrowth promoting
235Annex 1oftheTBTAgreement defines atechnical regulation asa"Document which laysdown product characteristics
ortheir related processes andproduction methods ...withwhich compliance isnecessary ...".WT/DS48/R/CAN
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hormones. What remained tobedetermined bythePanel waswhether theseobstacles weremore trade-
restrictive thannecessary tofulfil alegitimate objective.
4.315 Canada recalled itsprevious arguments that(paragraph 4.6),theECmeasures weremotivated
byfoursetsofconcerns: first, anxiety regarding thedanger tohuman health; second, thepressure
ofpublic opinion; third, theeconomic consequences ofa"sensationalist campaign"; andfourth, the
distortions intheconditions ofcompetition among theECmember States owing todissimilar provisions
andregulations governing themanufacture, distribution anduseofsubstances. Canada argued that
while protection ofhuman health wasamong thepolicy objectives listed inArticle 2.2,thisinitself
didnotjustify acomplete import prohibition. AsCanada haddemonstrated, theECimport prohibition
lacked scientific justification. TheEuropean Communities hadfailed toprove thatanimport prohibition
wasnecessary toprovide protection tothehealth ofitsconsumers. Furthermore, ithadalsobeen
demonstrated (seeparagraphs 4.42, 4.54, 4.225) thattheEuropean Communities maintained regulatory
control overantimicrobial growth promoters thatwassignificantly lessrestrictive totrade thanthe
complete banontheuseforgrowth promotion ofthesixgrowth promoting hormones andtheimport
prohibition ofbeefproduced outside theEuropean Communities withthesame hormones. Thus the
ECmeasures weremore trade restrictive thannecessary, incontravention ofArticle 2.2oftheTBT
Agreement.
4.316 CanadaclaimedthatapanelexaminingameasureunderArticle2.1mustdetermineifthemeasure
inquestion wasameasure towhich theprovision applied (i.e.whether itwasatechnical regulation),
iftheproducts inquestion werelikeproducts, andifthemeasure resulted inlessfavourable treatment
fortheimported Canadian product thanforthelikedomestic andimported products.
4.317 Canada noted thatArticle 2.1oftheTBT Agreement incorporated thenon-discrimination
principles setoutinGATT Articles IandIIIbutwasbroader. There wasnolanguage inArticle 2.1
thatqualified orlimited thescope ofthenon-discrimination obligations intheTBTAgreement. While
Article 2.1wasbroader thanGATT Articles IandIII,there wasanobvious linkbetween these
provisions. Although apanel assessing theconsistency ofameasure withArticle 2.1might beguided
generally bythetypeofanalysis thatmight beconducted under GATT Articles IandIII,itwasnot
required toadhere rigidly totheprecise formofsuchanalysis. InCanada 'sview, beefproduced with
growth promoting hormones wasa"likeproduct" tobeefproduced intheEuropean Communities from
animals towhich thesamegrowth promoting hormones hadbeenadministered fortherapeutic reasons,
and"like" beefthatcontained residues ofantimicrobial growth promoters andother veterinary drugs.
Canada submitted thatbyexcluding Canadian beeffromtheECmarket, theEuropean Communities
hadtreated Canadian products lessfavourably thanlikeproducts ofECorigin, incontravention of
Article 2.2oftheTBTAgreement.
4.318 TheEuropean Communities reaffirmed thatthemain purpose ofthemeasures atissue was
toprotect human health fromtherisksarising fromtheconsumption ofmeatfromanimals treated with
growth promoting hormones. Inviewofthedefinition ofSPSmeasures under theSPSAgreement,
theEuropean Communities considered ittobebeyond doubt thatthemeasures atissuewere"sanitary
measures" within themeaning oftheSPSAgreement. Therefore, theECarguments onTBTwere,
liketheCanadian arguments, presented inthealternative. If,thePanel decided thatthemeasures at
issue were not"sanitary measures" but"technical regulations" subject totheTBTAgreement, the
European Communities submitted that, contrary toCanada 'sclaims, theydidnotinfringe either
Article 2.1orArticle 2.2ofthatAgreement.
4.319 Article 2.1oftheTBT Agreement restated thenational treatment obligation contained in
Article III:4ofGATT andthemost favoured nation obligation contained inArticle I:1ofGATT.
TheEuropean Communities claimed thatasfarasthenational treatment obligation wasconcerned (the
onlyonewhose violation hadbeen invoked byCanada), Article 2.1oftheTBT Agreement and
Article III:4ofGATT laiddown thesametypeofobligation: nottoafford "lessfavourable treatment"WT/DS48/R/CAN
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toimported products thantodomestic likeproducts. Theonlydifference between thetwoprovisions
wasthatArticle 2.1oftheTBTAgreement applied onlyinrespect oftechnical regulations, while
Article III:4ofGATT applied inrespect of"alllaws, regulations andrequirements ...". Itfollowed
thatnoviolation ofArticle 2.1could beestablished unless Article III:4ofGATT wassimultaneously
infringed. Forthesame reasons thatthemeasures atissue didnotinfringe Article III:4oftheGATT
(paragraph 4.337 ff.),ECmeasures were consistent withArticle 2.1oftheTBTAgreement.
4.320 Theprimary purpose oftheECmeasures wastoprotect human health. Thiswasoneofthe
"legitimate objective" expressly mentioned inArticle 2.2oftheTBTAgreement. Asevidenced by
theprecedent discussion ontheapplication oftheSPSAgreement, theECmeasures were notmore
"trade restrictive" thannecessary inorder tofulfilthisobjective. Therefore, theEuropean Communities
maintained itsmeasures were consistent withArticle 2.2oftheTBTAgreement.
4. GATT
(a) Article III
4.321 Canada submitted thattheECmeasures contravened Article IIIorXIofGATT. Although
itconsidered thatthere wasathreshold question under theGATT whether thismatter wasgoverned
byArticle IIIbyvirtue oftheInterpretive Note AdArticle III,orbyArticle XI,Canada wasofthe
viewthatthismatter would bemore appropriately addressed under Article IIIthanArticle XI.
4.322 Canada recalled thatArticle III:1ofGATT readasfollows:
"The contracting parties recognize thatinternal taxes andother internal charges, andlaws,
regulations andrequirements affecting theinternal sale, offering forsale, purchase,
transportation, distribution oruseofproducts ,andinternal quantitative regulations requiring
themixture, processing oruseofproducts inspecified amounts orproportions, should not
beapplied toimported ordomestic products soastoafford protection todomestic production"
(emphasis added).
4.323 TheAppellate Body, initsdecision in"Japanese Liquor Tax"236hadcommented onthe
relationship between Article III:1andtheother paragraphs ofArticle IIIasfollows:
"Article III:1oftheGATT articulates ageneral principle thatinternal measures should not
beapplied soastoafford protection todomestic production. Thisgeneral principle informs
therestofArticle III."237
4.324 Canada argued thatinthepresent casethemostrelevant partofArticle III:4wasparagraph 4,
which provided:
"Theproducts oftheterritory ofanycontracting party imported intotheterritory ofanyother
contracting party shall beaccorded treatment nolessfavourable thanthataccorded tolike
products ofnational origin inrespect ofalllaws, regulations andrequirements affecting their
internal sale,offering forsale,purchase, transportation, distribution oruse..."
4.325 Thereport oftheAppellate Body in"Japanese Liquor Tax" hadcitedwithapproval the1970
WorkingPartyReporton"BorderTaxAdjustments"assettingoutthe"...basicapproachforinterpreting
236"Japan -Taxes onAlcoholic Beverages" (AB-1996-2; WT/DS8/AB/R; WT/DS10/AB/R; WT/DS11/AB/R;
4October 1996).
237Idem.,p.18.WT/DS48/R/CAN
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"likeorsimilar products" generally inthevarious provisions oftheGATT 1947".238TheAppellate
Body hadquoted thefollowing passage ofthereport oftheWorking Party:
"(...) theinterpretation oftheterms should beexamined onacase-by-case basis. Thiswould
allow afairassessment ineachcaseofthedifferent elements thatconstitute a'similar 'product.
Some criteria weresuggested fordetermining, onacase-by-case basis, whether aproduct is
"similar": theproduct 'send-uses inagiven market; consumers 'tastes andhabits, which change
from country tocountry; theproduct 'sproperties, nature andquality (...)."239
4.326 TheAppellate Body, inthesame case, hadfurther commented ontheteststodetermine what
constituted a"like product", inparticular inthecontext ofArticle III:2:
"Nooneapproach toexercising judgement willbeappropriate forallcases. Thecriteria in
"Border TaxAdjustments" should beexamined, butthere canbenooneprecise andabsolute
definition ofwhatis"like". Theconcept of"likeness" isarelative onethatevokes theimage
ofanaccordion. Theaccordion of"likeness" stretches andsqueezes indifferent places as
different provisions oftheWTO Agreement areapplied. Thewidth oftheaccordion inany
oneofthose places mustbedetermined bytheparticular provision inwhich theterm"like"
isencountered aswellasbythecontext andcircumstances thatprevail inanygiven caseto
which thatprovision mayapply. Webelieve that,inthecontext ofArticle III:2, firstsentence
oftheGATT 1994, theaccordion of"likeness" ismeant tobenarrowly squeezed."240
4.327 Applyingtheflexibleapproachofthe1970WorkingPartyReporton"BorderTaxAdjustments",
different indications oflikeness hadbeen invoked byvarious GATT 1947 Panels, e.g.tariff
classification241,end-uses242orphysicalcharacteristicsoftheproduct.243CanadaarguedthattheEuropean
Communitiesdidnotdifferentiateinitstariffclassificationbetweenbeefproducedwithgrowthpromoting
hormones, antimicrobial growth promoters oranyother veterinary drugs, andbeefproduced without.
Similarly, intheECmeat-grading system nosuchdifferentiation wasmade.244
4.328 In"Japanese Liquor Tax", theAppellate Body ruled, agreeing withthePanel, thattheterm
"like products" inthefirstsentence ofArticle III:2should beconstrued narrowly.245Theruleof
Article III:4ofGATT waslessspecific thantherulesofArticle III:2. Therefore, the"likeness" test
ofArticle III:4ofGATT wasprobably intended tobelessstringent thanthatofArticle III:2. Even
applying themore stringent testofArticle III:2, Canada submitted thatitsbeefwasalikeproduct when
compared withECbeef.
238Idem.,p.20.
239Report oftheWorking Party on"Border TaxAdjustments", L/3464, adopted on2December 1970, BISD 18S/97,
102, para. 18.
240Appellate Body, "Japan -Taxes onAlcoholic Beverages" (AB-1996-2), p.21.
241Forexample, seethe1978 panel report on"EC-Animal Feed Proteins", BISD 25S/49, 63,paras. 5.47-5.49.
242Forexample, seethe1987 panel report on"United States -Taxes onPetroleum andCertain Imported Substances",
BISD 34S/136, 154-155, para. 5.1.1.
243Forexample, seethe1992 panel report on"US-Measures Affecting Alcoholic andMalt Beverages", which held
thatlowalcohol beerandhighalcohol beerwere likeproducts, BISD 39S/206, 293-294, para. 5.71-5.74.
244Regulations 1208/81/EEC, 2930/81/EEC and1026/91/EEC.
245WT/DS8/AB/R; WT/DS10/AB/R; WT/DS11/AB/R, pp.19 and20.WT/DS48/R/CAN
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4.329 Canada emphasized thatinthepresent context "likeness" wasnotthesameas"being identical".
Theburden wasnotonCanada toprove thatbeefproduced withgrowth promoting hormones was
thesameasotherbeef. Rather, Canada mustprove thatbeefproduced withgrowth promoting hormones
wassufficiently similar toECbeef, i.e.beefcontaining residues ofantimicrobial growth promoters
andotherveterinary drugs, toestablish thatanational treatment violation hasoccurred. Canada referred
toanECdocument entitled "Communication fromtheCommission totheCouncil andtotheEuropean
Parliamentoncontrolofresiduesinmeat-Hormones-Beta-Agonists-OtherSubstances",whichstated:
4.330 "The results oftheenquiry [onresidues inmeat, initiated bytheCommission, following a
request oftheEuropean Parliament] showed that:
- anabolic substances (hormones andbeta-agonists) were generally available, leading
toillegal use;
- antibiotic andsulphonamide residues werefrequently found inmeat,especially inthe
caseofintensive livestock rearing systems (vealcalves, young fattening bovines, and
fattening pigs);
- otherresidues weredetected occasionally (heavy metals including cadmium, pesticides,
antiparasitic substances) ..."246(emphasis added).
4.331 Canada claimed thatthephysical characteristics ofbeefproduced from animals treated with
growth promoting hormones wereindistinguishable fortheconsumer frombeefproduced without the
useofgrowth promoting hormones. Theuseofgrowth promoting hormones resulted inbeefofhigher
quality because theanimals concerned hadbetter carcass composition, withagreater lean-to-fat tissue
ratio. Thishadbeenconfirmed intheabove-mentioned Communication fromtheCommission tothe
Council.247Chemical analysis ofthebeefmight beabletoidentify beefproduced fromanimals treated
withgrowth promoting hormones incertain instances. However, adocument commissioned and
published bytheCommission admitted thatthiswasvirtually impossible withregard tooestradiol-17 ,
testosterone andprogesterone. Thereport commented inthisregard:
"Toourpresent knowledge uptonowdistinctions between untreated animals andthose treated
withoestradiol-17 ,testosterone andprogesterone canonlybemade onaquantitative and
notaqualitative basis.Thisstatement isbased onthefactthatthethree steroids mentioned
above (oestradiol-17 ,testosterone andprogesterone) willenterthesamemetabolic pathways,
regardless ofwhether theyareofendogenous orexogenous origin. Thus treated animals can
onlybeidentified iftheirtissue levels significantly exceed those ofuntreated animals; ifsuch
asituation isdetected itfurther hastobeverified thattheparticular animal showing thislevels
[sic]wasclinically sound andthatnoreproductive problems, suchascystic ovaries ortumours
ofsexhormone producing organs hadbeenpresent atslaughter"248(emphasis added).
246Communication from theCommission totheCouncil andtotheEuropean Parliament onControl ofResidues inMeat -
Hormones -Beta-Agonists -Other Substances COM(93) 167final21April 1993, para. 5.
247Ibid..,para. 23.
248R.J.Heitzman, ed.,"Veterinary Drug Residues: Residues infoodproducing animals andtheirproducts: Reference
Materials andMethods", 2nded.,(Oxford: Blackwell Scientific Publications, 1994), p.7/5.WT/DS48/R/CAN
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4.332 A1987 Monograph issued bytheJECFA hadconfirmed theabove conclusion inrespect of
progesterone.249Thedifficulty ofdistinguishing beefproduced withthethreenatural growth promoting
hormones from other beefhadalsobeenconfirmed ina1994 article byDr.Stephen F.Sundlof.250
4.333 Canada claimed thatthisshowed thatitwasverydifficult, ifnotimpossible, todistinguish,
eventhrough chemical analysis, between beefproduced withnatural growth promoting hormones and
beefproduced without; andthatthesedifferences inproduction methods didnotresult inproducts that
were"unlike" beefproduced intheEuropean Communities. Inanyevent, theEuropean Communities
continued topermit theuseofoestradiol-17 ,progesterone andtestosterone fortherapeutic purposes
andhadnotprohibited thesaleandconsumption ofthebeefderived fromanimals treated withthese
hormones. Thisreinforced thepoint thatitwasdifficult, ifnotimpossible, todistinguish inthe
European Communities between beeffromcattle thathadbeentreated withthese hormones andthose
thathadnot.
4.334 Canada argued thatgiven thatbeefcontaining residues ofantimicrobial growth promoters and
otherveterinarydrugswaswidelyavailableintheECmarket,itwouldnotbeappropriate,indetermining
the"likeness" ofCanadian andECbeef,tolimitthecomparison ofbeefproduced withgrowth promoting
hormones tobeeffromcattle thatwereraised without theuseofantimicrobial growth promoters and
other veterinary drugs. Canada hadshown (seeparagraph 4.259) thattheuseofantimicrobial growth
promoters andotherveterinary drugs intheEuropean Communities resulted inthepresence ofresidues
inbeefsoldthere. Thepresence ofantibiotic andsulphonamide residues, aswellasother residues
inmeat, hadbeenconfirmed intheCommunication from theECCommission totheECCouncil.
TheEuropean Communities themselves, intheirgrading system ofbeef, didnotdistinguish between
beefproduced withandwithout growth hormones, orbetween beefwithresidues ofantimicrobial growth
promoters andother veterinary drugs andthatwithout.
4.335 Canada submitted that given theother residues present inbeef produced inthe
European Communities, Canadian beefproduced withthesixgrowth promoting hormones atissue
wasa"likeproduct" within themeaning ofArticle III:4oftheGATT ascompared tobeefproduced
intheEuropean Communities; andthatCanadian beefhadbeenaccorded treatment thatwasless
favourable thanECbeef, incontravention ofArticle III:4oftheGATT.
249"Residues ofsome veterinary drugs inanimals andfoods", Monographs prepared bytheThirty-Second Meeting of
theJoint FAO/WHO Expert Committee onFood Additives, Rome, 15-23 June1987, FAO Food andNutrition Paper 41
(Rome: FAO, 1988) p.22:
"Aswithother endogenous steroid hormones, residue levels ofprogesterone intissues areverylow.
Progesterone levels were measured intissues from treated steers using aradio-immunoassay technique
sensitive atthelowng/kg level, andwere found tobeabout 0.4µg/kg inmuscle, liverandkidney and
3.5µg/kg infat;these levels canbecompared withnormal levels ofapproximately 0.2µg/kg inmuscle,
liver andkidney andapproximately 2.5µg/kg infatfrom untreated animals.
"Progesterone, likeoestradiol-17 andtestosterone, occurs naturally inmammals, andisnormally present
inthedairy products andthetissues ofuntreated animals. Intheedible tissues ofanimals treated with
progesterone incombination withoestradiol-17 ,residue levels areuptotwice ashighasinthetissue
ofuntreated animals. However, thelevels ofprogesterone found inthemeat from animals treated with
implants according togood animal husbandry practice areextremely lowwhen compared totheamounts
ofendogenous progesterone produced daily inhuman beings. Thedaily production rateofprogesterone
inhumans isgiven inTable VII. (Farber andArcos, 1983). Even inprepubertal boys, the300ng
additional progesterone derived from a500gportion ofmeat from treated animals isconsiderably less
thantheamount ofendogenous progesterone produced daily. Inaddition, forthose animal classes studied,
theprogesterone residue levels intreated animals fellwellwithin thenormal range oflevels found in
untreated bovine animals ofdifferent types andages."
250S.F.Sundlof, "Human Health Risks Associated withDrug Residues inAnimal-Derived Foods" (1994) 1:2Journal
ofAgromedicine 5,pp.12-13.WT/DS48/R/CAN
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4.336 TheEuropean Communities argued thatthemeasures atissuehadtheirdomestic counterpart
intheprohibition ontheadministration ofthesametypes ofhormones toanimals reared intheEuropean
Communities andintheprohibition onthemarketing ofthose animals andofmeatfromthose animals.
Themeasures applied todomestic products hadidentical scope andweresubject tothesameexceptions
asthemeasures applied totheimported products. Theonlydifference between themeasures applied
todomestic products andthose applied toimported products wasthatwhile theformer wereapplied
atthestage ofproduction andsale,thelatter wereenforced atthepoint ofimportation. Furthermore,
themeasures applied toboth domestic andimported products as"products", eveniftheirscope was
defined interms ofprocesses andproduction methods ("PPMs") rather thaninterms ofproduct
characteristics. Thepresent casewastobedistinguished from thesituation considered bythepanel
report on"US-Restrictions onImports ofTuna I",inwhich thepanel hadreasoned thattheNote
adArticle IIIcovered onlythose measures which were"applied toproducts assuch". Yet,according
tothepanel, theUSinternal regulations "could notpossibly affect tuna"asaproduct ".251Incontrast,
inthepresent casethereason forprohibiting theimportation ofanimals which hadbeentreated with
certain hormones, andofmeatfromthose animals (aswellastheirdomestic production andsale)was
precisely thatthistreatment, unlike thePPMs forfishing tunaprescribed bytheUSregulations, modified
thephysical characteristics andbiological composition oftheproducts.
4.337 TheEuropean Communities disagreed withtheCanadian interpretation of"like products".
IntheECview, adetermination of"likeness" mustbeexclusively based onobjective criteria related
tothecharacteristics oftheproducts. Thepurpose ofaregulatory distinction between "likeproducts"
might onlybecome relevant indeciding whether ameasure which wasinconsistent withArticle III:4
could bejustified under anyofthegeneral exceptions provided forunder Article XXoftheGATT.
TheEuropean Communities contended thatthepurpose ofthemeasures atissue wasnottoafford
protection todomestic production buttoprotect human andanimal health, aswellastheinterests of
consumers and,therefore, would not,inconformity withtheCanada 'sowntest,infringe Article III:4.
Although twoproducts neednotbeidentical inorder tobe"like" forthepurposes ofArticle III,previous
panel reports hadtaken aconsistently narrow approach when interpreting thisterm. In"EC-Measures
onAnimal Feed Proteins", thepanel hadrejected aclaim bytheUnited States totheeffect thatall
products usedforthepurpose ofadding proteins toanimal feeds were"like". Thepanel noted, inter
alia,thattheproducts concerned haddifferent protein contents anddifferent origins (vegetal, animal
orsynthetic).252More recently, thepanel report on"Japan -Taxes onAlcoholic Beverages", acase
concerning theapplication ofArticle III:2, hadconcluded that:
"...onlyvodka could beconsidered aslikeproduct toshochu since, apart from
commonality ofenduses, itshared with shochu most physical characteristics.
Definitionally, theonlydifference isinthemedia usedforfiltration. Substantial
noticeable differences inphysical characteristics existbetween therestofthealcoholic
beverages atdispute andshochu thatwould disqualify them from being regarded as
likeproducts. More specifically, theuseofadditives would disqualify liqueurs, gin
andgenever; theuseofingredients would disqualify rum;lastly, appearance (arising
from manufacturing processes) would disqualify whisky andbrandy"253(emphasis
added).
251Panel report on"US-Restrictions onImports ofTuna I",DS21/R (unadopted), 3September 1991, 39S/155, 193-195,
paras. 5.8-5.14.
252Panel report on"EC-Animal Feed Proteins", para4.2. Theother Panel report dealing witharegulatory measure
discriminating between non-identical products isthePanel report on"US-Measures affecting Alcoholic andMaltBeverages".
Inthiscase, thepanel found thatlowalcohol andhighalcohol beerwere "similar" interms ofphysical characteristics but
were not"like" forthepurposes ofArticle III:4because thedistinction wasnotapplied soastoafford protection todomestic
production, BISD 39/206, pp.93-295, paras. 5.70-5.77.
253Panel report on"Japan -Taxes onAlcoholic Beverages", para. 6.23.WT/DS48/R/CAN
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4.338 TheEuropean Communities reaffirmed itsviews thatmeatfrom animals towhich hadbeen
administeredanyofthesixhormonesatissueforgrowthpromotionhadsubstantiallydifferentproperties,
composition andappearance thanmeatfromanimals towhich thosehormones hadnotbeenadministered
ortowhich theyhadbeenadministered onlyfortherapeutic purposes. Moreover, meatfromtreated
animals wasperceived byECconsumers asadistinct product. Forthesereasons, animals treated with
hormones forgrowth promotion, andmeatfromthose animals, could not,inlightofthecriteria used
byprevious panel reports, beconsidered as"like" toother animals, andmeatfromthose animals, for
thepurposes ofArticle III:4.
4.339 TheEuropean Communities added thatmeatfrom animals treated withanyofthehormones
atissueforgrowth promotion wasdifferent frommeatfromuntreated animals orfromanimals treated
fortherapeutical purposes inseveral ways. First, theprecise mode ofaction oftheprohibited hormones
wasnotyetunderstood. Itcould notbeexcluded, onthebasis oftheavailable scientific evidence,
thattheymight actasgenotoxic agents thatinduced permanent genetic mutations inthose animals to
which theywereadministered. Thepresence ofresidues which werepotentially genotoxic rendered
themeatunfitforhuman consumption. Meat which fromthesanitary point ofviewwasnotallowed
tobeconsumed andhormone-free meatcould notunder anycircumstance bedefined tobe"like" for
thepurposes ofArticle III:4ofGATT. Inaddition, trenbolone, zeranol andMGA werenotnaturally
producedbyanimals.Thus,meatfromanimalstowhichthesehormoneshadbeenadministeredcontained
residues ofhormones which were notfound inmeat from other animals, including animals treated
fortherapeutic purposes, towhich onlynatural hormones could beadministered. Inaddition, meat
fromanimals treated withthese hormones contained metabolites fromthese hormones which didnot
appear inmeatfrom other animals.
4.340 TheEuropean Communities further maintained thatmeatfrom animals towhich anyofthe
threenatural hormones hadbeenadministered forgrowth promotion contained alevelofresidues which
wasinexcess ofthelevel thatitwould otherwise contain. Moreover, asadmitted byCanada, the
residues might bepresent indifferent proportions fromthose found innature, forexample higher levels
ofmalehormones infemale animals andvice-versa254.Furthermore, meatfromanimals treated with
thesehormones wasmore likely tocontain anunusually highlevelofresidues thanmeatfromuntreated
animals, inparticular where thehormones hadbeenadministered combined in"cocktails" orindisregard
ofgoodanimal husbandry practices. Obviously, thisriskwasdominated orreduced when thehormones
were administered fortherapeutic purposes under veterinary control.
4.341 Inaddition, carcasses from animals treated withhormones might differ infatcontent, fat
composition, water content andconnective tissue fromthose ofuntreated animals. Combinations of
androgens andoestrogens, andandrogens alone, decreased fatcontent andincreased water content,
whereascombinationsofprogestagensandoestrogensincreasedfatcontent,particularlyinmaleanimals.
Theuseoftrenbolone andoestrogen decreased theamount ofconnective tissue andunsaturated fatty
acidinmuscle. Cocktails ofprogestagens andoestrogens altered therelative proportions ofsaturated
andunsaturated fatintreated carcases. Ingeneral, anabolic steroids hada"partitioning" effect, resulting
inthedeposition incarcasses ofabout 8percentmore protein and12percentlessfat.255
4.342 TheEuropean Communities argued thatevenifanimals treated withhormones forgrowth
promotion, andmeatthereof, andother animals, andmeatthereof, werefound tobe"likeproducts",
itsmeasures would stillbeconsistent withArticle III:4because theyafforded identical treatment to
254TheEuropean Communities noted that,atpara. 130ofitsfirstsubmission tothePanel, Canada admitted that"for
thepurposes ofgrowth promotion, animals areadministered those hormones inwhich theyaredeficient. Generally, forgrowth
promotion purposes, males aregiven oestrogens andgestagens, andfemales aregiven androgens".
2551995 ECScientific Conference Proceedings, pp.74-75 and242.WT/DS48/R/CAN
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imported products andtodomestic likeproducts. TheEuropean Communities recalled thatCanada
hadadvanced twotypes ofarguments inorder tojustify itsclaim thatbeeffromanimals treated with
anyofthesixth growth promoting hormones andother beefwere "like":
(i) thatresidues from oestradiol, testosterone andprogesterone administered toanimals
wereindistinguishable fromresidues ofthesesubstances naturally produced byanimals;
and
(ii) thatECmeat from untreated animals contained residues ofantimicrobial growth
promoters andother veterinary drugs.
4.343 TheEuropean Communities argued thatthefirstofthese twoarguments wasflawed. Inthe
firstplace, itdidnotaccount forthepresence ofresidues ofthethreesynthetic hormones inmeatfrom
treated animals. These residues were notfound inmeat from untreated animals andwere readily
distinguishable from theresidues ofthethree natural hormones. Second, thefactthattheresidues
from administered hormones could notbeeasily distinguished from theresidues ofthose hormones
naturally produced byanimals didnotmean thatthere werenodifferences between thetwotypes of
meat. There weresubstantial differences between them. Thetechnical difficulties toidentify theorigin
oftheresidues hadrendered itnecessary fortheEuropean Communities torequire from importers
acertification thatanimals hadnotbeentreated, instead ofconducting inspection ofmeatatitsborders,
butitdidnotmake thetwotypes ofmeat"like".
4.344 Thesecondargumentwasequallymisguided.AstheEuropeanCommunitieshaddemonstrated,
hormones andantimicrobial growth promoters andother veterinary drugs were different substances
andposeddifferentriskstohumanhealth.Consequently,meatwhichcontainedresiduesofantimicrobial
growth promoters andother veterinary drugs wasnot"like" meat which contained residues of
administered growth promoting hormones.
4.345 TheEuropean Communities disagreed withtheCanadian interpretation ofArticle III:4. The
wording ofArticle III:4called foracomparison between thetreatment given to"theproducts ofthe
territory ofanycontracting party imported intotheterritory ofanyother contracting party ..."and
thetreatment accorded to"likeproducts ofnational origin ...",andnotbetween thetreatment given
to"anyimported product" andthetreatment accorded to"anydomestic likeproduct". Theordinary
meaning ofArticle III:4didnotrequire thatacomparison bemade onanimport-by-import basis, but
acomparison ofthetreatment given toallimported products asawhole vis-a-vis alldomestic like
products asawhole. IntheECview, theobject andpurpose ofArticle IIIhadbeenmade explicit
inthegeneral principle setforthinthefirstparagraph ofthatArticle, which stated thatinternal taxes
andregulations "should notbeapplied toimported ordomestic products soastoafford protection
todomestic production". Article III:4gaveeffect tothisprinciple withrespect tointernal regulations,
other thantaxregulations andmixing regulations, andshould beinterpreted inconformity withit.
Where aninternal regulation laiddown different requirements forimported anddomestic products,
itmight beassumed thatdomestic production was"protected" ifanyimported product received "less
favourable treatment".256
4.346 TheEuropean Communities argued thatthesituation wasdifferent where, asinthepresent
case, theinternal regulation didnotdistinguish between imported anddomestic products butbetween
different types oflikeproducts, irrespective oftheirorigin. Themere factthataninternal regulation
accorded morefavourable treatment tocertain typesoflikeproducts vis-a-vis othertypesoflikeproducts
256Hence the"no-balancing" principle established byprevious Panel reports which havedealtwithformally discriminatory
internal regulations. Seepanel report on"United States -Section 337oftheTariff Actof1930", adopted on7November
1989, 36S/345, 387, atpara.5.14; andpanel report on"US-Standards forReformulated Gasoline", WT/DS2/R,
paras. 6.14-6.15.WT/DS48/R/CAN
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didnotnecessarily mean thatdomestic production ofthelikeproduct aswhole wasprotected. For
that,itwould benecessary thatthose types oflikeproduct which were accorded more favourable
treatment wereinherently oratleastpredominantly domestic and/or thatthetypes which received less
favourable treatment were inherently oratleastpredominantly imported. Thisviewwassupported
inthepanel report on"US-Measures affecting Alcoholic andMaltBeverages", which stated that:
"The Panel recognized thatonthebasisoftheirphysical characteristics, lowalcohol beerand
highalcohol beerwere similar. Itthenproceeded toexamine whether, inthecontext of
Article III,thisdifferentiation intreatment oflowalcohol beerandhighalcohol beerissuch
"astoafford protection todomestic production". ThePanel firstnoted thatbothCanadian
andUnited States beermanufacturers produce bothhighandlowalcohol beer. Itthennoted
thatthelawsandregulations inquestion invarious states donotdifferentiate between imported
anddomestic beerassuch,sothatwhere astatelawlimits thepoints ofsaleofhighalcohol
content beerormaintains different labelling requirements forsuchbeer, thatlawapplies to
allhighalcohol content, regardless ofitsorigin. Theburdens resulting fromthese regulations
thusdonotfallmoreheavily onCanadian thanonUnited States producers "257(emphasis added).
4.347 Although intheECview thepanel report on"US-Measures affecting Alcoholic andMalt
Beverages" erred byascribing theanalysis oftheeffects ofameasure tothedetermination whether
twoproducts were"like" andnotexclusively onthecharacteristics oftheproducts, thispanel report
confirmed thatArticle III:4wasnotinfringed unless aregulatory distinction between likeproducts
hadtheeffect ofprotecting domestic production.
4.348 Withreference totheECargument thattheperception ofEuropean consumers wasarelevant
factor indetermining the"likeness" ofaproduct, Canada submitted thatthisfactor wasirrelevant.
Thepublic authorities ofWTO Members hadaresponsibility toeducate thepublic andtomake them
aware ofscientific facts. IfthePanel weretoallow "public perception" tobecome afactor ina"like
product"determination,itwouldopenthedoortomisapprehensionsconcerningscientificfactsbecoming
thebasis ofajustification intheWTO fortheadoption ofdiscriminatory measures. Such an
interpretation would obviously remove anyincentive whatsoever forpublic authorities intheEuropean
Communities tomake theirpopulations aware ofthescientific factsinrespect ofthesixhormones
atissue.
4.349 Canada observed thatthe1987panel report in"Japan -Customs Duties, Taxes andLabelling
Practices onImported Wines andAlcoholic Beverages"258dealt withtheissue oftherelevance of
consumer preferences ina"likeproduct" determination forpurposes ofGATT Article III:2. The1987
finding, which wascitedwithapproval bytherecent panel onthesamesubject matter259wasthat"...the
traditional Japanese consumer habits withregard toshochu provided noreason fornotconsidering
vodka tobea'like'product. ..."Thus, inthecontext ofArticle III:2, twopanels hadexpressly rejected
therelevanceofconsumerperceptionina"likeproduct"determination.Canadasubmittedthatconsumer
perception wasequally irrelevant inthecontext ofGATT Article III:4.
4.350 Canada pointed outthattheissueofwhether regulatory differentiation of"likeproducts" could
bejustified under Article III:4wasdiscussed bythepanel report on"United States -Standards for
Reformulated andConventional Gasoline".260Having found that"chemically-identical imported and
257Panel report on"US-Measures affecting Alcoholic andMalt Beverages", para. 5.73 .
258BISD 34S/83, para. 5.7.
259"Japan -Taxes onAlcoholic Beverages", WT/DS8/R; WT/DS10/R; WT/DS11/R, para.6.23, footnote 103.
260WT/DS2/R, 29January 1996.WT/DS48/R/CAN
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domestic gasoline arelikeproducts under Article III:4"261,thepanel hadtodealwiththeUSargument
"that therequirements ofArticle III:4[were] metbecause imported gasoline [was] treated similarly
togasoline fromsimilarly situated domestic parties -domestic refiners withlimited 1990 operations
andblenders".262Thepanel rejected thisargument.263According toCanada, although thefactsin
thiscasewere different, itwasuseful toquote thePanel'scaution inresponse totheUSattempt to
justify regulatory differentiation:
"Apart from being contrary totheordinary meaning oftheterms ofArticle III:4, any
interpretation ofArticle III:4inthismanner would mean thatthetreatment ofimported and
domestic goods concerned could nolonger beassured ontheobjective basis oftheirlikeness
asproducts. Rather, imported goods would beexposed toahighly subjective andvariable
treatment according toextraneous factors. Thiswould thereby create great instability and
uncertaintyintheconditionsofcompetitionasbetweendomesticandimportedgoodsinamanner
fundamentally inconsistent withtheobject andpurpose ofArticle III."264
ThusCanada submitted thatregulatory differentiation bytheEuropean Communities between beeffrom
cattle towhich thesixhormones atissue hadbeenadministered forgrowth promoting purposes and
other beef, i.e.,likeproducts, placed theCanadian beefatissue atacompetitive disadvantage and
assuchwasinconsistent withArticle III:4.
4.351 Inanyevent, evenarguendo accepting theECreliance onthepanel report in"United States -
Measures Affecting Alcoholic andMaltBeverages", Canada submitted thatthepanel report didnot
support theECproposition. TheEuropean Communities ignored thefollowing paragraph inthesame
report thatdirectly contradicted theirargument:
"The Panel recognized thatthetreatment ofimported anddomestic products aslikeproducts
under Article IIImayhavesignificant implications forthescope ofobligations under theGeneral
Agreement andfortheregulatory autonomy ofcontracting parties withrespect totheirinternal
taxlawsandregulations: onceproducts aredesignated aslikeproducts, aregulatory product
differentiation, e.g.forstandardization orenvironmental purposes becomes inconsistent with
Article IIIeven iftheregulation isnot"applied ...soasafford protection todomestic
production" .Intheview ofthePanel, therefore, itisimperative thatthelikeproduct
determination inthecontext ofArticle IIIbemade insuchawaythatitnotunnecessarily infringe
upon theregulatory authority anddomestic policy options ofcontracting parties. ThePanel
recalled itsearlier statement thatalikeproduct determination under Article IIIdoesnotprejudge
likeproduct determinations made under other Articles oftheGeneral Agreement orinother
legislative contexts" (emphasis added).265
261Ibid.,para. 6.9.
262Ibid.,para. 6.11. Thereport explains further:
According totheUnited States, thedifference intreatment between imported anddomestic gasoline was
justified because importers, likedomestic refiners withlimited 1990 operations andblenders, could not
reliably establish their1990 gasoline quality, lacked consistent sources andquality ofgasoline, orhad
theflexibility tomeet astatutory baseline since theywere notconstrained byrefinery equipment and
crude supplies.
263Ibid.,seealsoparas. 6.13-6.16.
264Ibid.,para. 6.12. Thepanel report in"United States -Standards forReformulated andConventional Gasoline" was
thesubject ofanappeal. Theappeal, however, dealt onlywithissues related toArticle XXanddidnotconcern thePanel 's
conclusions regarding Article III:4. Thereport oftheAppellate Body iscontained inWT/DS2/AB/R, 29April 1996.
265Panel report on"US-Measures Affecting Alcoholic andMalt Beverages", BISD 39/206, para. 5.72.WT/DS48/R/CAN
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4.352 Canada therefore submitted thatCanadian beefandECbeefwere"likeproducts" within the
meaning ofGATT Article III:4andtheEuropean Communities could not,consistent withthatprovision,
bantheimportation ofCanadian beefproduced withthesixhormones atissue.
4.353 TheEuropean Communities recalled itsprevious arguments onArticle IIIanddisagreed with
Canada 'scontention thatmeattreated withhormones andhormone-free meatwerelikebecause they
"contain comparable residues". Itignored thepotential hazards which these residues posed tohuman
andanimal health. Itwastheposition oftheEuropean Communities thatthesetwotypes ofmeatwere
notlikebecause hormone-treated meat might cause cancer. Indeed, meat containing residues of
exogenously administered hormones wasnotdifferent from meatinfected withadisease. The1987
panel report on"Japan -Customs Duties, Taxes andLabelling Practices onImported Wines and
Alcoholic Beverages" referred to"traditional Japanese consumer habits". ThewishoftheECconsumers
toeathormone-free meatwasnotahabitandwasnottraditional. Itevolved fromanumber ofexamples
reported intheEuropean Communities andelsewhere (e.g.Puerto RicoandtheUnited States) ofthe
hazards arising from theuseofthese hormones, which hadbeenscientifically documented.
(b) Article XI
4.354 Canada claimed that,inthealternative, theECimport prohibition infringed GATT Article XI,
butnoted thatthisclaim should onlybeconsidered bythePanel ifitdecided thatArticle IIIofGATT
didnotapply inthiscase. Article XIofGATT setouttheobligations ofMembers withrespect to
thegeneral elimination ofquantitative restrictions. Article XI:2provided forlimited exceptions to
thegeneral prohibition ofArticle XI:1, none ofwhich were applicable inthiscase. Thus the
EuropeanCommunitieswereprohibitedfrombanningtheimportofbeefproducedwithgrowthhormones
andhadinfringed Article XIoftheGATT.
4.355 TheEuropean Communities responded thatthemeasures atissue wereinternal regulations
within thescope ofArticle IIIofGATT. Therefore, Article XIofGATT didnotapply.
(c) Article XX
4.356 Canada claimed thatArticle XXoftheGATT didnotjustify theinfringement demonstrated
above ofArticle IIIorArticle XI.
4.357 TheEuropeanCommunitiessubmittedthatincasethePanelweretofindthatmeasuresinfringed
Article III:4,theysatisfied therequirements oftheSPSAgreement and,consequently, mustbepresumed
tobeinaccordance withGATT, andinparticular withtheprovisions ofArticle XX(b).
5. Nullification andimpairment
4.358 Canada claimed thattheinconsistency oftheECmeasures withtheSPSAgreement andthe
GATT, orinthealternative withtheTBTAgreement, established aprima faciecaseofnullification
orimpairment pursuant toGATT Article XXIII:1(a) andArticle 3.8oftheDSU.266However, even
ifthePanel were todecide thattheECmeasures were consistent withtheWTO Agreement, the
application oftheECmeasures nullified orimpaired benefits accruing toCanada under theWTO
Agreement, within themeaning ofArticle XXIII:1(b) oftheGATT 1994. Article XXIII:1(b) hadbeen
interpreted inGATT 1947 practice tomean evenifameasure wasnotinconsistent withaprovision
oftheGATT, itmight bechallenged asnullifying orimpairing benefits. Article 26(1) oftheDSU
266Previous GATT 1947panels haddetermined thataprima faciecaseofnullification andimpairment isestablished where
there isaninfringement ofobligations under theGATT. TheDSU codifies thisinArticle 3.8which provides thatwhere
obligations under anagreement suchastheGATT ortheTBTAgreement areinfringed, theaction isconsidered prima facie
toconstitute acaseofnullification orimpairment.WT/DS48/R/CAN
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made itclear thatcomplaints concerning non-violation nullification andimpairment could bemade
within thenewframework oftheWTO Agreement. Traditionally, three conditions wererequired by
GATT1947panelsfordeterminingwhetheracaseof"non-violation"nullificationorimpairmentexisted.
These conditions were:
(i) thenegotiation ofatariff concession;
(ii) thesubsequent introduction ofagovernment measure thatupset thecompetitive
relationship between thebound product withregard tolikeordirectly competitive
imported products; and
(iii) thatthemeasure atissuecould nothavebeenreasonably anticipated atthetimeofthe
negotiation ofthetariff concession.267
4.359 Inthepresent case, alloftherelevant tariff items were subject totariff concessions bythe
European Communities.268These concessions included Canadian access toatariff ratequota of
11,500 tonnes, withaninquota rateof20percent, forhighquality, fresh, chilled orfrozen beef
allocated toCanada andtheUnited States (the"Hilton beefquota").269
4.360 TheHiltonbeefquotahadoriginallybeengrantedbytheEuropeanEconomicCommunityduring
theTokyo Round Multilateral Trade Negotiations (contained intheEuropean Economic Community
schedule ofconcessions annexed totheGeneva (1979) Protocol), prior totheevents which ultimately
ledtotheEChormone ban.TheHilton beefquota originally wasa10,000 tonne levyfreetariffquota.270
When theHilton beefquota wasestablished, theEuropean Community hadadopted regulations which
excluded Canadian highquality beeffromitsscope, which hadledtotheestablishment ofapanel at
therequest ofCanada. Thepanel hadruled inCanada 'sfavour, andthisreport hadbeenadopted by
theGATT Council inMarch 1981.271TheEuropean Community subsequently amended itsregulations
toallow Canadian highquality beefaccess under theHilton beefquota. Asaresult oftheUruguay
Round Trade Negotiations, theEuropean Communities converted theHilton beefquota tothetariff
ratequota asindicated above. Subsequently, intheArticle XXIV negotiations of1995, duetothe
accession ofFinland, Sweden andAustria totheEuropean Communities, theEuropean Communities
increased theHilton beefquota to11,500 tonnes.272
267See"EC-Payments andSubsidies PaidtoProcessors andProducers ofOilseeds andRelated Animal-Feed Proteins",
report ofthepanel adopted on25January 1990, BISD 37S/86, paras. 142-154.
268Uruguay Round Schedule LXXX -European Communities, PartIMost Favoured-Nation Tariff, Section I-Agricultural
Products, Section IATariffs andSection IBTariff Quotas, assubsequently modified. Tariff items covered bytheECbeef
andvealregime are:
02011050; 02012015; 02012035; 02012055; 02012090; 02013000; 02021000; 02022010; 02022030;
02022050; 02022090; 02023010; 02023050; 02023090; 02061010; 02061091; 02061095; 02061099;
02062100; 02062210; 02062290; 02062910; 02062991; 02062999; 02102010; 02102090; 02109041;
02109049; 16025010; 16025090; 16029061; and16029069.
269Schedule CXL -European Communities, PartIMost-Favoured-Nation Tariff, Section I-Agricultural Products,
Section IBTariff Quotas.
270"European Economic Community -Imports ofBeef" from Canada, BISD 28S/92.
271Ibid..
272Therefore, Canada maintained theincrease intheHilton beefquota didnotamount toarebalancing ofconcessions
between Canada andtheEuropean Communities. See"EC-Payments andSubsidies PaidtoProcessors andProducers
ofOilseeds andRelated Animal-Feed Proteins", report ofthepanel adopted on25January 1990, BISD 37S/86, para. 145.WT/DS48/R/CAN
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4.361 Thus, thefirstrequirement ofthetraditional analysis ofGATT 1947 panels hadbeenmet.
Second, theintroduction oftheECmeasures hadupset thecompetitive relationship between Canadian
andECbeef. Third, atthetimewhen Canada hadwonaccess totheHilton beefquota, itcould not
havereasonably foreseen theintroduction oftheECmeasures. Therefore, Canada claimed thatbenefits
accruing toitunder theWTO Agreement hadbeennullified orimpaired.
4.362 TheEuropean Communities responded thatCanada failed tomeettheminimum requirements
providedforinArticle26oftheDSUasregardedadetailedjustificationofanynon-violationcomplaints.
Inthepresent case, Canada 'sclaim ofnon-violation nullification andimpairment wasunwarranted
forthefollowing reasons:
(i) the"benefits" invoked byCanada onlyaccrued toCanada aftertheadoption ofthe
measures atissue;
(ii) inanyevent, themeasures could havereasonably beenanticipated byCanada atthe
timewhen, according toCanada, thebenefits accrued; and
(iii) Canada hadnotprovided anyjustification foritsclaim thatthecompetitive relationship
betweendomesticandimportedproductshadbeenupsetbytheadoptionofthemeasures.
Infact,theconsistency ofthemeasures withtheWTO Agreements citedbyCanada
presupposed thatthemeasures were notcapable ofhaving suchaneffect.
4.363 TheEuropean Communities argued thattheso-called "Hilton beefquota" granted bythe
European Economic Community during theTokyo Round hadbeenwithdrawn during theUruguay
Round negotiations andreplaced byanewpackage ofconcessions onthesame product. These new
concessions hadbecome binding upon theEuropean Communities longaftertheintroduction ofthe
measures atissue. Thus, Canada could notclaim thatthese newconcessions hadbeennullified or
impaired bythemeasures atissue.273
4.364 During theUruguay Round, theEuropean Communities hadreplaced thistariff quota byan
entirely newpackage ofconcessions, butithaddone sointhecontext ofthenewAgreement on
Agriculture. Under theAgreement onAgriculture, Members hadagreed toachieve specific binding
commitments intheareasofmarket access, domestic support andmarket competition. Theconcessions
outlined below musttherefore beseenasnewconcessions negotiated inthecontext ofanewAgreement:
- first,variable levies onimports ofbeefhadbeeneliminated aspartofthe"tariffication
process";
- second, theEuropean Communities hadbound therateoftheordinary customs duties
applicable onallimports ofbeef.Theinitial bound ratewas20percentplusaspecific
amount ranging from 2763 ECU to4740 ECU pertonne, depending onthetypeof
beef. Thefinalbound ratewas12.8percentplusanspecific amount, ranging from
1768 ECU to2652 ECU pertonne;
273TheEuropean Communities explained thatasregarded Canada, theconcessions granted bytheEuropean Economic
Community during theTokyo Round negotiations withrespect toimports ofbeefconsisted ofa10,000 tontariff quota for
highquality beefwithanin-quota rateof20percent. Inaddition, imports within thisquota were freefrom thevariable
levyapplied atthetimebytheEuropean Economic Community. Noother tariff concessions hadbeen granted bythe
European Economic Community withrespect toimports ofbeef. Accordingly, imports ofbeefoutside thequota weresubject
tocustoms duties andagricultural levies attherateautonomously established bytheEuropean Economic Community.WT/DS48/R/CAN
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- third, theEuropean Communities hadopened a10,000 tonne tariff quota withan
in-quota rateof20percentallocated toCanada andtheUnited States.
4.365 Thisnewpackage ofconcessions onimports ofbeefwassubstantially different from, andmore
"valuable" than, theTokyo Round concessions onthesame product. Itrepresented anewconcession
which hadreplaced theTokyo Round concession onthesame product andwaspartofanew"balance
ofconcessions" achieved bytheparties during theUruguay Round. Theadditional benefits obtained
byCanada must beregarded asthecounterpart forCanada 'sownconcessions, including the
renouncement byCanada toanyoutstanding non-violation rights withrespect totheTokyo Round tariff
quota, which wasimplicit inCanada 'sconsent tothereplacement oftheoldconcession bythenew
package ofconcessions.
4.366 IntheECview, thepresent casewastobedistinguished fromthecaseconsidered bythepanel
onEC-Oilseeds. Inthatcase,thepanel hadfound thatontheoccasion ofArticle XXIV:6 negotiations
following thesuccessive enlargements oftheCommunity, theconcessions atissue hadnotbeen
"modified" butrather "extended" tothenewECmember States. Forthisreason, thepanel had
concluded that,despite theformal modification oftheschedules ofconcessions, theoriginal "balance
ofconcessions" hadnotbeenaltered. Hence theexpectations created when theconcessions hadbeen
originally granted continued tobeprotected.274However, theEuropean Communities argued thatthe
present casediffered fromtheEC-Oilseeds caseintwofundamental respects. Firstly, inthepresent
casetheUruguay Round tariff concessions onbeefweresubstantially different fromthepre-existing
concessions onthesame product since theyweremarket access concessions asenvisaged inArticle 4
oftheAgreement onAgriculture, anewAgreement. Secondly, thenewconcessions onbeefwere
granted aspartofanegotiated exchange ofconcessions; intheEC-Oilseeds case, onlyoneparty
wasrequired tomake concessions. Thefindings oftheEC-Oilseeds panel weretherefore inapplicable
tothepresent case.
4.367 TheEuropean Communities argued thatinanycase,themeasures atissuecould havereasonably
been anticipated byCanada already atthetimeoftheTokyo Round. Because there existed no
international standards, guidelines orrecommendations ontheuseofhormones asgrowth promoters
in1979, Canada could notreasonably assume thattheEuropean Economic Community would nottake
anymeasures inorder torestrict theirusetoanimals ormeatfromanimals. Sanitary concerns about
theuseofhormones asgrowth promoters predated theTokyo Round. When theHilton beefquota
hadbeennegotiated, Canada wasaware thatthesafety ofusing hormones asgrowth promoters was
questioned insome scientific circles aswellasbyconsumer organizations andthegeneral public.
Canada wasalsoaware that,prompted bythose concerns, amajority ofECmember States, aswell
asother countries, hadalready taken steps torestrict theuseofhormones.
4.368 TheEuropean Communities claimed thatCanada hadnotadvanced anyjustification whatsoever
foritsclaim thattheECmeasures hadupset thecompetitive relationship between domestic products
andimports. Inthisregard, theCanadian submission failed tomeettheminimum requirements provided
forinArticle 26oftheDSU. Unlike "violation" cases, in"non-violation" cases there wasno
presumption of"nullification andimpairment". Theburden ofproving thatthemeasures atissuehad
infactupset thecompetitive relationship between domestic andimported products laywithCanada.
4.369 Canada claimed thattheHilton beefquota wasnotthesubject ofexplicit negotiations between
Canada andtheEuropean Communities during theUruguay Round. Intheagricultural areatheUruguay
Round hadmade acleardistinction between tariffratequotas thatconfirmed pre-existing access rights
274Panel report on"EC-Payments andSubsidies PaidtoProcessors andProducers ofOilseeds andRelated Animal
Feed Proteins", adopted 25January 1990, BISD 37S/86.WT/DS48/R/CAN
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andnewaccess rights.275Thecurrent tariff ratequota waslisted intheSchedule oftheEuropean
Communities under theheading of“Current Access Quotas ”.276Thus theHilton beefquota clearly
fellwithin thecategory ofquotas under which existing market access opportunities weremaintained.
Canada argued thatevenifscientific concerns could havebeenanticipated in1979, Canada could hardly
haveforeseenthattheEuropeanCommunitieswouldadoptthemosttrade-restrictivemeasuresimaginable,
i.e.,atotalbanontheimportation ofbeeffrom cattle towhich anyofthesixhormones atissue had
beenadministered forgrowth promoting purposes. Furthermore, oftheECmember States thatbanned
theuseofgrowth promoting hormones before theECbancame intoeffect, atleastone,Denmark,
andpossibly others aswell, didnotprohibit theimportation ofbeefproduced withthehormones at
issue. Canada hadsubmitted detailed information onthedevastating impact oftheECmeasures at
issueonitsbeefexportstotheEuropeanCommunities(paragraph4.28).277Therefore,Canadasubmitted
thattheEuropean Communities hadnullified orimpaired Canada 'srights within themeaning of
Article XXIII:1(b) oftheGATT.
4.370 TheEuropean Communities responded thatCanada failed tomeettheminimum requirements
provided forinArticle 26oftheDSUasregards adetailed justification insupport ofanynon-violation
complaint. Nojustification whatsoever wasadvanced fortheclaim thattheECmeasures hadupset
thecompetitive relationship between domestic production andimports. AsforCanada 'sargument
thatthequota of11,500 tonnes allocated totheUnited States andCanada wasacurrent access quota
and,hence, "falls under thecategory ofquotas under which existing market opportunities were
maintained", theEuropean Communities noted thattheterm"current access" wasatermusedduring
theUruguay Round negotiations forthepurpose ofdrawing upmarket access commitments, inthe
context oftheGuidelines which hadbeendeveloped foragriculture negotiations. Suchguidelines had
become obsolete oncetheUruguay Round Schedules were finalized andtheFinal Actwassigned.
Infact,theprovisions oftheAgreement onAgriculture contained noreference to"current access"
asaspecific kindofcommitment, butonlyreferred to"market access commitments" (Article 4.1).
TheEuropeanCommunities,therefore,reiteratedthatthequotacontainedintheUruguayRoundSchedule
waspartofawhole newbalance ofconcessions, inthecontext ofawholly newagreement, the
Agreement onAgriculture. Withregard tothepretended nullification orimpairment ofbenefits accruing
toCanada, theEuropean Communities argued thatprevious totheUruguay Round, theonlyGATT
commitment thattheEuropean Communities hadwithrespect tothetarifflinesconcerned wastheTokyo
Round commitments onhighquality beeftariff quotas, including the10,000 quota towhich Canada
successively gained access. Nocommitment existed foranybeefoutside ofhighquality meat. Claims
advanced byCanada concerning nullification orimpairment ofbenefits asregarded commitments on
thetariff linesmentioned above were, therefore, incorrect. Atthetimeofthenegotiation ofthese
concessions, themeasures atissue were already inexistence.
V. THIRD PARTIES SUBMISSIONS
1. Australia
5.1 Australia noted thatithadsetoutitsviews ontherelationship between theECbanonthe
importation ofhormone growth promotant treated meatanditsobligations under theSPSAgreement
275GATT Press Release NUR 080, 14December 1993, ontheFinal ActoftheUruguay Round, p.9.
276Schedule CXL oftheEuropean Communities (Schedule LXXX attheendoftheUruguay Round), Section I-BTariff
Quotas.
277Atthesecond meeting oftheParties withthepanel, Canada produced atable which setforth eleven tariff lines of
theEuropean Communities (020610; 02061010; 02062210; 02062910; 02061091; 02062290; 02061099; 02062100;
02062999; 02109049; 16025090; 16029069) withregard tobeefproducts which were bound prior totheUruguay Round
andthetrade figures foreach ofthese tariff lines from 1984 through 1995.WT/DS48/R/CAN
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initssubmission of27September tothepanel inregard tothecomplaint bytheUnited States. Australia
saidthatitssubmission tothepanel inregard tothecomplaint byCanada wasintended tosupplement
thisearlier submission byproviding asummary ofthekeylegalissues andaddressing several issues
raised intheECsubmission of23December tothepanel considering theCanadian complaint.
5.2 Australia indicated thatasamajor exporter ofmeatand,inrecent years, theworld 'slargest
beefexporter ithadamajor trade interest inthismatter. Stressing itsspecific interest intheECbeef
market, Australia noted thatithadmanaged tocontinue itstradewiththeEuropean Communities despite
theimplementation ofCouncil Directive 88/146/EEC bythedevelopment ofanHormone Growth
Promotion (HGP) control system. Thissystem hadallowed Australian cattle producers whowished
tocontinue totradewiththeEuropean Communities todoso,but,atthesametimetobeabletoaccess
andusehormones forgrowth promotion purposes forothermarkets thatdidnotimpose suchrestrictions.
ThishadbeenatacosttotheAustralian industry ofabout $A10 million ayear. However, Australia
hadnever accepted thelegitimacy oftheECmeasures. Noting thatthepurpose ofthethreeDirectives
wastheprotection ofhuman lifeorhealth andthattheprohibition ontheimportation fromthirdcountries
ofmeatfrom animals towhich hormones hadbeenadministered wasasanitary measure asdefined
bytheSPSAgreement, Australia claimed thattheconsistency oftheECmeasures withECobligations
should beconsidered against theprovisions oftheSPSAgreement which required thatSPSmeasures
"shall bedeveloped andapplied inaccordance withtheprovisions ofthisAgreement" (Article 1.1).
5.3 Australia argued thattheSPSAgreement established, interalia,thebasicrights andobligations
ofMembers inrespect ofsanitary measures necessary fortheprotection ofhuman lifeandhealth which
maydirectly orindirectly affect international trade. Notwithstanding anyother WTO rights and
obligations, Australia considered thatifaMember wereacting inconsistently withitsobligations under
theSPSAgreement, itstood inbreach ofitsWTO obligations. Inaddition, astheSPSAgreement
represented anelaboration oftheGATT inrespect ofSPSmeasures andasconformity withSPS
obligations gaverisetoapresumption ofconformity withArticle XX(b) oftheGATT, Australia
consideredthattheECmeasuresshouldbeexaminedinthefirstinstanceagainsttherightsandobligations
oftheSPSAgreement asitwasthisagreement which established thebasic rights andobligations of
Members inrespect ofSPSmeasures.
5.4 Australia placed particular stress onthefactthatinobserving thataninternational standard
asprovided forinArticle 3.1oftheSPSAgreement existed inrelation totheEChormone ban,the
EuropeanCommunitieshadfailedtodemonstrateitscompliancewithArticle3.3.Inparticular,Australia
argued thattheEuropean Communities hadfailed todemonstrate either thatthere wasascientific
justification foritsadoption ofmeasures resulting inahigher levelofprotection orthatithadcarried
outanexamination andevaluation ofavailable scientific evidence, including inaccordance withthe
relevant provisions ofArticle 5toshow thattheinternational standard wasnotsufficient toachieve
itsappropriate levelofprotection.
5.5 Referringtotheconclusionsofthe1995ECScientificConference(seeparagraph2.33),Australia
argued thatalthough these conclusions provided clear support totheview thatthefivesubstances
considered attheConference weresafetousewithin theconditions specified inAustralia andwithin
theCodexstandards,theEuropeanCommunitieshadconfusinglyclaimedthat"...Thescientificevidence
forthenecessity tomaintain ourmeasures istheevidence from the1995 Scientific Conference ...".
TheEuropean Communities hadmade noattempt tosubstantiate itsassertion ortoexplain the
contradiction between thisstatement andtheConference conclusions.
5.6 Although theEuropean Communities hadasserted thatforthenatural hormones itwasknown
thattheyhaveadverse effects, which combined withalackofknowledge oftheiraction, lackofdata
ontheeffect ofcombinations andthelackofdefinition of"good veterinary practice", permit the
European Communities toadopt adifferent levelofprotection, i.e.ensure theECconsumers thatthere
arenoresidues leftother thanthenaturally produced onesbytheanimals themselves", Australia arguedWT/DS48/R/CAN
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thattheEuropean Communities hadfailed toestablish thatthese statements reflected thefindings of
ariskassessment oranexamination andevaluation ofavailable scientific information inconformity
withtheprovisions oftheSPSAgreement. TheEuropean Communities hadalsonotestablished the
basisforitsclaim thattherewasalackofdefinition of"good veterinary practice", which wasgenerally
taken tomean using veterinary chemicals inaccordance withconditions ofregistration, including
observing intended purpose, correct doseratesandwithholding periods thatweredetermined bythe
technical registration process.
5.7 Withregard totheECarguments thathormones hadserious adverse effects onhealth including
cancer, Australia noted thatsuchclaims hadalsobeenmade inrespect ofdrugs containing hormonal
substances which were directly administered tohumans formedicinal purposes. TheEuropean
Communities hadnotexplained whyitpractised azeroriskpolicy intheissue under examination by
thePanel butnotinother comparable circumstances when itwasknown thatthehormonal product
would directly enterthehuman system. Good veterinary practice wasthebasisforuseofthehormones
atissue andtofocus onlyontheworst casescenario astheEuropean Communities haddonecould
render theuseofallveterinary chemicals illegal, justastheuseofallchemicals usedinhuman medicinal
preparations might bebanned. Furthermore, thestatement thattheintensive large-scale production
ofmeatrenderedeffectivecontrolofhormonegrowthpromoterstechnicallyandeconomicallyunfeasible,
flewinthefaceofthefactthatmajor meatexporting nations apart from theEuropean Communities
were abletoeffectively control inappropriate hormone usewithout theimposition ofatotalbanon
theuseofthesesubstances.AllagriculturalandveterinarychemicalsusedwithinAustraliamustundergo
assessment andregistration priortodistribution anduse.Thisrequired athorough assessment ofdetailed
technical datapackages bytheNational Registration Authority. Theoutcome ofregistration wasto
control theuse,labelling, packaging andsupply oftheproduct. Thiswasunderpinned bylegislation,
withpenalties where theseconditions werenotfollowed. Additionally, Australia backed upthesystem
withindividual property identification ofcattle tothepoint ofslaughter, aNational Residue Survey
toassess compliance withMRLs, andaNational Vendor Declaration system forcattle through which
vendors must declare thechemicals usedoncattle offered forsaleandthedateoftreatment.
5.8 Australia argued that,despite theEuropean Communities repeated claims tothecontrary, there
wasnoevidence thattheEuropean Communities hadundertaken ariskassessment onthismatter, in
accordance withtheprovisions ofArticle 5.TheEuropean Communities hadstated that"theEuropean
Communities hastwice formed groups ofscientists toexamine thehormones atissue". However, it
hadstated itself that"thepurpose ofthe1995 ECscientific Conference wasnottoperform forita
riskassessment, buttoprovide apublic forum fordiscussion ofthescientific aspects oftheuseof
growth promoters". Therefore, theEuropean Communities hadexplicitly accepted thatthisConference
wasnotpartofariskassessment process. AttheCanada/EC consultations on25July1996, atwhich
Australia waspresent asathird party, theECrepresentative hadsaidthatthere hadbeennorisk
assessment donesincetheLamming Committee andthatnowork hadbeendoneinthisareasince1988.
However, nowhere within theECfirstsubmission inthiscase, haditclaimed thattheLamming
Committee hadundertaken ariskassessment process which could beconsidered tohave metthe
requirements ofArticles 5.1and5.2.
5.9 Emphasizing thatArticle 5.4required Members, when determining theappropriate levelof
sanitary orphytosanitary protection, totakeintoaccount theobjective ofminimizing negative trade
effects, Australia submitted thattherewasnoevidence tosuggest thattheEuropean Communities had
taken intoaccount negative trade effects when imposing theprohibition onimports ofmeat treated
withhormones forgrowth promotion purposes. Thisprohibition hadimposed significant compliance
costs ontheAustralian meatindustry.
5.10 With regard toArticle 5.5,Australia argued thattheEuropean Communities hadfailed to
demonstrate itscompliance withthisprovision. "Consistency" didnotdemand aquantified levelof
risk,orthatMembers must havethesame levelofriskinrespect ofevery measure. However, theWT/DS48/R/CAN
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European Communities must justify whyithadadopted alower level ofriskinthiscasethanin
comparable circumstances. Australia agreed thatinageneral sense itwastruethat,through risk
management, eachcountry 'sacceptable levelofriskmight reflect societal values, but,asspecifically
stated byArticle 5.5,theacceptable levelofriskdetermined byacountry through thisprocess must
beapplied inaconsistent manner, andcould notbeapplied onanarbitrary orunjustifiable case-by-case
basis. Forexample, theEuropean Communities choosing toaccept zeroriskinthecaseofmeatfrom
animals treated withgrowth promoting hormones or,aspointed outbyCanada, apparent inconsistencies
between thelevelofprotection thattheEuropean Communities hadapplied toimports ofmeattowhich
hormones hadbeenadministered forgrowth promotion purposes, andthelevels ofprotection thatthe
European Communities applied totheuseofother growth promoters andveterinary drugs. These
distinctions inthelevels ofprotection would appear tobearbitrary andunjustifiable.
5.11 Australia furthermore argued thattheEuropean Communities hadfailed todemonstrate its
compliance withtheobligation ofArticle 5.6astherewould appear tobelesstraderestrictive approaches
toachieve theEuropean Communities 'appropriate levelofprotection. Itobserved thattheEuropean
Communities hadclaimed thatitsmeasures werenotprovisional: theyweredefinitive, andtherefore
submitted thatArticle 5.7oftheSPSAgreement wasnotrelevant inthiscase. Noting thatasthe
European Communities hadfailed tocomply withtheprovisions ofArticle 3.3,byfailing todemonstrate
thatthere wasascientific justification foritslevelofsanitary orphytosanitary protection orthatits
maintenance ofalevelofprotection higher thantherelevant international standard wasaconsequence
ofthelevelithaddetermined inaccordance withtheprovisions ofArticle 5,Australia concluded that
there mustbeapresumption thattheECmeasures werenotinconformity withthebasic obligations
ofArticles 2.2and2.3oftheSPSAgreement.
2. Norway
5.12 Norway argued thatthiscaseconcerned theright ofevery statetomake itsownsovereign
decision onthelevelofprotection itafforded itscitizens withrespect tohealth hazards. Thisprinciple
hadalways beenpartofGATT lawandseveral panels when deciding disputes related toArticle XX(b),
hadreaffirmed suchright.278TheSPSAgreement, within itsscope ofapplication, might beconsidered
anexemplification ofArticle XX(b). Thiswasnotacaseofdiscrimination between likeproducts,
ordiscrimination between producers from different countries. Thequestion waspurely oneof
reaffirming theMember ’srighttodecide, when arisktoitspopulation waspresent, thelimits tothe
risktowhich itwould expose itscitizens, anditsfreedom tochoose themeasure toachieve thisprotection
aslongasthemeasure itself wasconsistent withWTO obligations. Inaneraofincreasing consumer
concern overthesafety offoodandthepresence ofpotentially harmful residues from theuseof
veterinary drugs, pesticides etc.,andatatimewhen old"scientific truths" hadoften beenoverturned
bynewevidence, itwasofutmost importance thattheWTO uphold thisrightoftheStatetoprotect
itscitizens against therisksconnected withtheuseofsuchsubstances.
278Panel report on"US-Restrictions ontheImports ofTuna":
"The panel further noted thatArticle XX(b) allows each contracting party tosetitshuman, animal orplant life
orhealth standard .Theconditions setoutinArticle XX(b) which limits theresort tothisexception, namely that
themeasures taken must be"necessary" ...refer tothetrade measure requiring justification ...nottothelifeor
health standard chosen bythecontracting party.(...)".
Furthermore, theAppellate Body inthecase"US-Standards forReformulated andConventional Gasoline", initsconcluding
remarks stated:
"WTO Members havealarge measure ofautonomy todetermine theirownpolicies ontheenvironment (including
itsrelationships withtrade), theirenvironmental objectives andtheenvironment legislation theyenact andimplement.
Sofarasconcerns theWTO, theautonomy iscircumscribed onlybytheneed torespect therequirements ofthe
General Agreement andtheother covered agreements."WT/DS48/R/CAN
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5.13 Noting thattheSPSAgreement restated therightofaMember tosetitshealth standards in
itspreamble andinArticle 3.3,Norway argued thatitwasclearthataMember hadtherighttodetermine
thelevelofprotection itconsidered appropriate foritspopulation, subject togeneral WTO requirements
withrespect totheexistence ofarisk,andrequirements withrespect tojustification ofthemeasure
theStateapplied. Inthedetermining theappropriate levelofprotection, Norway argued theobligation
upontheMember wasonlytoshow thatarisktoitspopulation waspresent. Aslongastheexistence
ofsuchariskhadbeenestablished, theWTO wasonlyconcerned withthejustification ofthemeasure
theMember choose toapply toachieve thelevelofprotection ithaddeemed appropriate. According
toArticle XX(b), aswellasArticle 5.2oftheSPSAgreement, aMember didnothavetoscientifically
prove theextent oftherisk. TheMember onlyhadtoshow thatsuchariskexisted (riskidentification),
andthereafter itwasfortheMember todefine thelevelofprobability ofharm itwanted toassume,
beitzeroorgreater (riskmanagement).
5.14 AMember mustconsider present dayscientific evidence when making ariskassessment. Such
evidence might ascertain ordisprove therisk,andmight bemore orlesscomplete, butthiswasonly
oneoftheelements tobetaken intoaccount intheriskassessment. Other relevant elements might
bei.a.theexistence ofadequate testing methods andinternationally approved production methods or
control requirements. Norway argued thattheSPSAgreement didnotrequire aMember tobaseits
levels ofprotection solely onsuggested maximum tolerances presented incurrent scientific evidence.
Thecases referred bytheEuropean Commission initssubmissions clearly showed fromhistory how
often oldscientific "truths" hadbeendisproved bynewscientific evidence. Ithadnever beenthe
intention oftheGATT/WTO, norshould itbethetaskofthisPanel, toinfringe upon theMember 's
righttodecide tobeonthesafesidewhere current evidence didnotexclude beyond doubt apotential
risktohuman health.
5.15 NorwaystressedthatoncetherightoftheMembertodetermineitsappropriatelevelofprotection
wasreaffirmed, ithadtobeascertained thatthechosen measure complied withthegeneral obligations
spelled outintheGATT ortheSPSAgreement. InNorway 'sview, thetesttobeapplied according
toGATT Article XXandArticle 5oftheSPSAgreement wasthefollowing:
- themeasure wasnotapplied inamanner which would constitute ameans ofarbitrary
orunjustifiable discrimination between countries where thesameconditions prevailed;
- themeasure wasnotapplied inamanner which wasadisguised restriction on
international trade;
- themeasure wasnecessary, i.e.notmore trade restrictive thanrequired toachieve
theappropriatelevelofprotection,takingintoaccounttechnicalandeconomicfeasibility.
Having applied thistesttothemeasure, itsconsistency withtheWTO obligations should bereadily
ascertained.
5.16 Norway submitted thattheEuropean Communities hadtherighttosetitsownlevelofprotection
inthiscase,andatthechosen level. Ithadclearly shown theuncertainties related tothepossible harmful
effect oflongtermexposure tothesubstances atissueandhadclearly shown thatitsmeasure didnot
discriminate between countries, norhadthere beenanydisguised restriction oninternational trade.
Themeasure hadbeenapplied uniformly toallproducts containing thesubstances inquestion, bethey
domestic orforeign. Inselecting themeasure which wasnecessary tominimise thepotential risk(risk
management) soastoensure theappropriate levelofprotection (zero orother acceptable levelofrisk),
many factors hadtobetaken intoconsideration, ofwhich MRL wasbutone.Thetechnical feasibility
ofensuringadequatecontroloftheuseofthehormones,i.e.strictveterinarysupervisionofeachimplant,
wereofutmost importance, aswellasthetechnical feasibility ofcontrol oftheresidue levelinallthe
meat inquestion. Furthermore, theeconomic costofthemeasure must betaken intoaccount. AnWT/DS48/R/CAN
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MRL system withextensive controls andverifications attheproducer levelandatpoint ofimportation
might besoprohibitively expensive astoberuled out.TheEuropean Communities hadshown that
other measures thanthecontested banwerenotavailable toachieve theappropriate levelofprotection,
which wasconsequently notmore trade restrictive thannecessary.
3. NewZealand
5.17 NewZealand indicated thatitsthirdparty'ssubstantial interest inthiscasewasduetothefact
thatNewZealand wasanagricultural exporting nation andmeatexports formed asignificant portion
ofitstotalexports. Intheyearending December 1995, primary produce (e.g.meatandmeatproducts,
dairy, fish,fruitandvegetables etc)accounted for72.10 percentofNewZealand stotalmerchandise
exports (NZ$ FOB). Forthesame period, meatandmeatproducts accounted for15.99 percentof
NewZealand stotalmerchandise exports (NZ$ FOB). Accordingly, theproper implementation of
theSPSAgreementwasamatteroffundamentalimportancetoNewZealandandthepotentialforsanitary
orphytosanitary measures tobeusedasdisguised restrictions ontradeamajor concern. NewZealand
claimed thattheSPSAgreement wasanelaboration ofrelevant GATT provisions andArticles 2.1and
2.4oftheSPSAgreement established theprimacy ofthatAgreement indetermining theWTO legality
ofsanitaryorphytosanitarymeasures.Accordingly,thelegalityofameasurefallingwithinthedefinition
ofa"sanitary orphytosanitary measure" wastobedetermined inaccordance withtheprovisions of
theSPSAgreement.
5.18 Noting thattheEuropean Communities hadjustified theimport banonthebasis thatthe
importation ofmeatfromanimals treated withanyofthesubstances might posearisktohuman health
andsafety279,NewZealand concluded thatthebanappeared tobeameasure thatfellwithin thedefinition
ofa"sanitary orphytosanitary measure" asdefined intheSPSAgreement.280NewZealand noted that
Article 1oftheSPSAgreement didnotmake provision foranyMember toexclude specific sanitary
orphytosanitary measures from theambit oftheAgreement. Moreover, theeffect ofArticle XVI:4
oftheMarrakesh Agreement wastorequire Members toensure theconformity ofalltheirlaws,
regulations andadministrative practices withtheSPSAgreement. Accordingly, theimport banand
allother sanitary orphytosanitary measures affecting international tradeinplace within thejurisdiction
ofanyMember, were subject totherequirements oftheSPSAgreement.
5.19 With regard toArticle 2.2,NewZealand claimed thatnoevidence hadbeenproduced ofan
appreciable riskofanadverse health effect arising from theuseofanyofthesubstances. Even ifit
were tobeshown thatthere wasanappreciable risk,theEuropean Communities would berequired
todemonstrate thattheimport banwasnecessary toaddress it.Inthisregard, NewZealand noted
thattheEuropean Communities hadexpressed particular concern about theperceived risksassociated
withtheinappropriate orillegal useofhormonal growth promotants, particularly when used in
"combinations" or"cocktails". However, evenifitwasdemonstrated thatanappreciable riskexisted
from suchinappropriate orillegal use,theEuropean Communities would needtodemonstrate that
279New Zealand noted thatinthepreamble ofECCouncil Directive 81/602/EEC of31July1981 thebanning ofnew
licences foranabolic agents forgrowth promotion wascharacterised asbeing inthe"interests oftheconsumer" anditdiscussed
thepotential "harmful effects" oftheuseofthesubstances inquestion. ECCouncil Directives 85/649/EEC of31December
1985 and88/146/EEC of7March 1988 citedconcerns relating totheeffect onhuman health fromtheuseofhormonal growth
promotants. Thepreamble oftheProposal foraCouncil Regulation (93/C 302/06) on14October 1993stated thatthepresence
ofsuchsubstances "may bedangerous forconsumers andmayalsoaffect thequality offoodstuffs ofanimal origin". And
finally, ECCouncil Directives 96/22/EC and96/23/EC stateintheirpreambles thatsuchsubstances maybedangerous for
consumers.
280New Zealand argued thattheimport banwould alsobeinconsistent withArticle 2.2oftheTBT Agreement were it
notthatAgreement explicitly noted (inArticle 1.5)thatitdidnotcover sanitary orphytosanitary measures. Intheevent
thattheimport banwere determined tobeneither asanitary measure, noratechnical barrier totrade, theprovisions ofGATT
would thenneed tobeconsidered.WT/DS48/R/CAN
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abanonimports wasinfact"necessary" toaddress thisspecific concern. Finally, from thehistory
ofthescientific investigations intothefivesubstances, under intense scrutiny byscientists inthelast
twodecades, NewZealand didnotconsider thattheimportation bancould bepresented asbeing "based
onscientific principles" norsustained by"sufficient scientific evidence". Moreover, inthecaseof
thesixthsubstance, MGA, NewZealand wasnotaware oftheexistence ofanyscientific information
which would warrant theimport baninitsregard.281
5.20 NewZealand submitted thatscientific evidence demonstrated thatthelevelofhormones present
inmeat varied considerably. Meat from animals treated withthesubstances forgrowth promotion
hadasimilar range orevenlower hormonal residues thanmeatfromsome animals thathadnever been
treated. Additionally, theEuropean Communities allowed meatfrom animals thathadbeentreated
withthethree naturally occurring substances fortherapeutic purposes tobeproduced, imported and
marketed within theEuropean Communities.282NewZealand considered thatforthese reasons, EC
measures contravened Article 2.3oftheSPSAgreement.
5.21 NewZealand stressed thatCodex hadadopted international standards, satisfying itselfthatthere
wassufficient scientific basis. Itwasunclear what "available scientific information" theEuropean
Communities could relyontoprovide "scientific justification" fortheimport banandaselective
examination andevaluation ofavailable scientific information would notbesufficient tomeet the
requirements ofArticle 3.3.Moreover, there should beascientifically established risktohuman or
animal lifeorhealth before anydetermination could bemade astoaMember s"appropriate level
ofprotection". Inthiscase,theredidnotappear tohavebeenanyscientifically defensible determination
ofanappreciable riskinthecaseoftheimport ban.
5.22 NewZealand claimed thattheSPSAgreement didnotallow fortheadoption ofasanitary or
phytosanitary measure thatprovided forahigher levelofprotection thananinternational standard in
theabsence ofascientific justification orariskassessment process thathadidentified anappreciable
risk. Inthecaseofallsixhormones, therewould notappear tohavebeenanyECassessment, meeting
therequirements ofArticle 5,which hadidentified anysuchrisk. While itwasevident thatconsumers
intheEuropean Communities might harbour concerns about theuseofthese substances, consumer
perceptions astoriskdidnotprovide abasisfortheadoption ofmeasures under Article 5.Furthermore,
NewZealand submitted thattheusual ECriskassessment andevaluation processes forveterinary
medicinal products283,which might otherwise have ensured aconsistent approach asrequired by
Article 5.5,didnotform thebasis fortheECmeasures.284Equally, given thatmany other products
freelymarketedwithintheEuropeanCommunitiescontainedmuchhigherlevelsofthehormonalresidues
281NewZealand indicated thatbecause ofdiffering userequirements andcommercial factors, there were differences in
therange ofagricultural chemicals (such asMGA) registered around theworld andhence differences inthestandards contained
innational laws. Theabsence ofaninternational standard foraparticular substance should notinitselfbeseenasjustification
foraparticular import ban. Inaddition, itshould benoted thatArticle 4oftheSPSAgreement encouraged Members to
mutually recognise, forthepurposes oftrade, theequivalence ofdifferent sanitary orphytosanitary measures injurisdictions
other thantheir own.
282New Zealand indicated thatitunderstood thattheEuropean Communities hadnotsetanyADIs orMRLs formeat
from animals treated fortherapeutic purposes.
283New Zealand clarified thattheguidelines forassessments ofveterinary medicinal products were contained, atthat
time, inECCouncil Directives 81/851/EEC and81/852/EEC. There were alsoguidelines presented inaproposed draft
directive entitled "Testing ofmedicinal products fortheirmutagenic potential" andthiswaspublished asAnnex IIinthe
ECOfficial Journal C293/11 dated 5November 1984.
284New Zealand added that, furthermore, since thattime, theEuropean Communities hasnotutilised theapplicable
assessment andevaluation processes toassess theuseofthese substances forgrowth promotion although ithasassessed and
approved theiruseforother therapeutic purposes without stipulating anyMRLs (see, forexample, Commission Regulation
(EC) 3059/94 of15December 1994).WT/DS48/R/CAN
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thattheEuropean Communities wasseeking toavoid through theimport ban,there would appear,
intheabsence ofevidence tothecontrary, tobearbitrary andanomalous levels ofprotection inplace.
Finally, Article 5.6made itclearthatevenifitcould beshown thatthere wasanappreciable riskto
health, given thesignificant trade implications oftheimport ban,theEuropean Communities would
havehadtoconsider whether therewerealternative lesstraderestrictive measures thatcould beapplied
toaddress sucharisk. Noting thattheEuropean Communities didnotseektorelyonArticle 5.7,
which wasamanifestation ofthe"precautionary principle", asthebasisforitsimport ban,NewZealand
emphasized thatthepresent situation appeared tobeonewhere thescientific evidence wasneither
insufficient norinadequate.285Accordingly, thiswasclearly notaninstance where the"sufficient
evidence" standard could besubstituted with thelessrigorous standard of"available pertinent
information". ThefactthatCodex hadadopted aninternational standard would always create astrong
presumption thatsufficient scientific evidence existed.
4. United States
5.23 TheUnited States indicated thatithadastrong interest inthePanel’sreview oftheECmeasures
atissue, asdemonstrated bythesubmissions oftheUnited States tothePanel established attherequest
oftheUnited States.286TheUnited States hadsuffered significant adverse economic effects fromthe
ECmeasures. Furthermore, thePanel hadindicated thatitintended toconduct itsdeliberations on
thisdispute concurrently withitsdeliberations onthechallenge brought bytheUnited States. This
meant thatthePanel contemplated thatthefactsandarguments advanced intheCanadian proceeding
might affect thePanel’sreport intheUSproceeding. Asaresult, thearguments andfactspresented
inthisproceeding could beexpected tohaveasubstantial effect ontheinterests oftheUnited States
withrespect totheECmeasures. Accordingly, theUnited States requested thePanel toprovide the
United States withextended thirdparty rights inthisproceeding. TheUnited States requested:
5.24 (i) toreceive allofthesubmissions oftheparties tothedispute;
(ii) toobserve thewhole oftheproceedings atthesubstantive meetings ofthePanel with
theparties tothedispute andwiththeexperts; and
(iii) tomake abriefstatement atasuitable moment during thesecond substantive meeting.
5.25 TheUnited States stated thatthisrequest would accord totheUnited States rights equivalent
tothose accorded bythePanel onEuropean Communities -Régime fortheImportation, Saleand
Distribution ofBananas toCanada asathirdparty intheproceeding onbananas. IntheEC-Bananas
proceeding, thePanel hadconcluded thattheUnderstanding onRules andProcedures Governing the
Settlement ofDisputes (DSU) permitted suchanextension ofthirdparty rights. TheUSinterests in
thisproceedingwerefargreaterthanCanada'sinterestsintheEC-Bananasproceeding,andthuspresented
anevenmore compelling needforaccess toallfactsandarguments presented. Thepanel proceedings
intheCanadian complaint ontheEChormone bandirectly affected therights oftheUnited States
under theMarrakesh Agreement Establishing theWorld Trade Organization. Thatwasnotthecase
foranyofthethirdparties intheEC-Bananas proceeding. Neither Canada ’s,noranyotherthirdparty’s,
WTO rights wereatissueintheEC-Bananas proceeding. Furthermore, theUnited States wastheonly
party thatwould nothaveaccess tothesubmissions tothePanel inbothproceedings. Canada had
access toallthesubmissions intheUSproceeding because boththeUnited States andtheEuropean
285NewZealand noted thateventhe1995 ECScientific Conference which wasprocedurally defective asariskassessment
process inthatitexcluded certain relevant participants andinformation, nonetheless, concluded thatthere wassufficient
scientific information todetermine thatthefivegrowth promotant substances could beused safely.
286WT/DS26/6.WT/DS48/R/CAN
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Communities hadmade theirsubmissions public. TheEuropean Communities hadaccess toallthe
documents since itwasaparty tobothdisputes.
5.26 TheUnited States alsonoted thatitwasafundamental principle thatparties toaproceeding
should know thefactsorarguments thatmayinfluence thepanel inpreparing itsreport. Nowhere
didtheDSUprovide thatapanel might receive material fromanysource without disclosing thatmaterial
toadisputing party. Accordingly, ifinitsdeliberations intheUSproceeding, thePanel considered
materialssubmittedtoitbythepartiesintheCanadianproceeding,andthosematerialswerenotprovided
totheUnited States, thenthePanel would bebasing itsdeliberations intheUSproceeding onanex
parte communication prohibited byArticle 18.1oftheDSU.
5.27 TheUnited States indicated withrespect tothesubstance ofthedispute thatforallthereasons
provided intheproceeding ofthepanel established attherequest oftheUnited States, theUnited States
agreed withCanada thattheECmeasures atissue intheproceedings ofthisPanel wereinconsistent
withtheECobligations under theWTO Agreement, inparticular theSPSAgreement andGATT.
TheUnited States affirmed thearguments ithadalready made inthatproceeding andindicated that
theydidnotneedtobefurther elucidated inthispanel proceeding. Forthispurpose, theUnited States
incorporated allofthefactsandarguments presented bytheUnited States inthose proceedings. For
asummary ofthose factsandarguments, seethereport ofthePanel inthose proceedings.
5.28 With respect tothejointmeeting ofthePanel withtheUnited States, Canada, andthefive
scientific experts selected bythePanel toprovide information, advice, andtheiropinions oncertain
aspects ofthematter thatwasthesubject ofthedispute, theUnited States stated thattheadvice received
from theexperts helped toclarify theinconsistency oftheECbanwiththeprovisions oftheSPS
Agreement andtheGATT.
5.29 TheUnited States stated thatitwasclearthat,contrary toArticle 2.2oftheSPSAgreement,
theEuropean Communities didnothavesufficient scientific evidence tosupport itsban. Numerous
scientific reviews, evaluations andriskassessments hadbeenconducted withrespect tothesixhormones
involved inthisdispute. Fiveofthehormones hadbeenevaluated bothbynational regulatory authorities
inWTO Members andbytheCodex Alimentarius Commission, theentity designated bytheSPS
Agreement astheinternational standard setting bodyforfoodsafety. Allofthose reviews concluded
thatthescientificevidenceestablishedthatresiduesinmeatofthesehormonesusedforgrowthpromotion
inaccordance withgood practice weresafe. Thesixthhormone, MGA, hadbeenreviewed byWTO
Member national regulatory authorities whohadalsoconcluded thatMGA residues from growth
promotion inaccordance withgoodpractice weresafe. While therawdatawereproprietary, theresults
andconclusions oftherelevant studies wereavailable inthepublished literature aswellasfrom the
USFood andDrug Administration (FDA). Asummary ofallthestudies were available aspublic
documents.
5.30 TheUnited States argued thattheEuropean Communities putallthisevidence asideandoffered
instead somedatathatitclaimed weresufficient toshowthatthesehormones weregenotoxic carcinogens
andtheEuropean Communities claimed thatthiswould mean thatnoresidue ofthese hormones from
growth promotion would beacceptable. With respect totherelevance ofthisdata,theUnited States
stated thatfirst,thedatafromDr.Liehr applied onlytooneofthesixhormones involved inthisdispute -
oestradiol-17ß. Itdidnotinvolve theother fivehormones. Second, Dr.Liehr’sstudies werenotnew,
theywere conducted prior totheJECFA report andwere referenced inthatreport.
5.31 TheUnited States observed thatthedatapresented asevidence thatoestradiol-17ß wasgenotoxic
concerned DNA adducts (these werecompounds bound toDNA thatwerenotsupposed tobethere).
These adducts occurred inthekidney ofmale Syrian hamsters following treatment withhighdoses
ofoestradiol-17ß. Regulatory scientists thatwereresponsible forprotecting thehealth ofconsumers
relied ontestsakintotestslikethese (so-called "short-term assays") asascreen todetermine whetherWT/DS48/R/CAN
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carcinogenicity studies were warranted. They were notsufficient toserve asabasis forregulatory
action. Furthermore, positive results inoneofthese short-term assays didnotmean thatacompound
wasagenotoxic carcinogen.
5.32 TheUnited States explained thatadetermination ofcarcinogenicity required long-term testing
inliveanimals. Thestandard model fordetermining carcinogenicity wasatestcalled a"two year
rodent bioassay." Itwasconducted inmaleandfemale ratsandmice. Amore definitive test-atwo-
yearrodent bioassay hadalready beenconducted foroestradiol-17ß. Theresults ofthebioassay together
withtheresults ofother short-term testshadbeenreviewed byvarious scientific experts andusedin
determining thesafety ofoestradiol-17ß. Based ontheresults ofthesetestsandotherrelevant scientific
data,ithadbeendetermined thatoestradiol-17ß wasnotagenotoxic carcinogen. Since long-term in
vivocarcinogenicity testshadalready beenconducted forthesehormones, theresults ofadditional short-
termassays were oflittlevalue. Inother words, thefullscientific process necessary tomake the
regulatory decision thatoestradiol wasnotagenotoxic carcinogen hadalready beencompleted. The
verylowlevels ofoestradiol-17ß present infoodwerenotadding tothecancer riskofwomen, children
ormen. Moreover, two-year rodent bioassays hadalsoalready beenconducted ontrenbolone and
zeranol andalsoestablished thatthese were notgenotoxic carcinogens.
5.33 TheUnited States alsoobserved thatiftheECdatawerecorrect, thenitcould notbeunderstood
whytheEuropean Communities would permit theuseofthesamehormones forzootechnical purposes.
TheUnited States explained that"zootechnical" referred tosuchmatters assynchronizing theestrus
cycles inaherd. Thisinvolved administering hormones tohealthy animals. Ithadnothing todowith
treating disease. Itwasdonesolely fortheconvenience ofthefarmer. Itwasaneconomic purpose
whose objective wastoproduce more animals (thatis,produce more meatorother animal products)
more efficiently. ThiswaswhytheUnited States hadusedthelesstechnical, more accurate term"herd
management" withrespect tothese uses.
5.34 Inaddition,theUnitedStatesstatedthatintheUnitedStateseachsponsorofanapprovedproduct
hadanongoing burden todemonstrate thesafety ofthatproduct. There wasacontinuing review of
thescientific datarelated tothatproduct. Nodatahadarisen toaltertheFDA determination thatthese
sixhormones were safewhen usedforgrowth promotion inaccordance withgood practice.
5.35 TheUnited States observed thatinthisdispute theEuropean Communities hadlargely ignored
MGA. Ithadoffered noscientific evidence insupport ofitsbanonMGA andhadessentially admitted
thatithadnever studied MGA.
5.36 TheUnited States further stated thattheexperts selected bythePanel hadconfirmed that:
(i) Thethree natural hormones administered forgrowth promotion purposes were
chemically identical tothethree natural hormones produced bytheanimal andby
humans andtothethree natural hormones permitted bytheEuropean Communities
tobeadministered forzootechnical andtherapeutic purposes. Inother words, for
purposes ofthehealth ofaconsumer eating themeat, itdidnotmatter whytheresidue
wasthere, itwasstillthesame chemical.
(ii) Theresidues inmeatwerewithin thenormal physiological levels forthethree natural
hormones when administered forgrowth promotion purposes inaccordance withgood
animal husbandry practice. Again, inother words, twoconsumers could beexposed
totheidentical levelofhormones residues eventhough oneateonlybanned meatand
theother ateonlynon-banned meat. Indeed, theconsumer eating ECmeatcould well
beexposed tosubstantially higher levels ofhormone residues thantheconsumer eating
onlybanned meat.WT/DS48/R/CAN
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(iii) There would always beresidues ofahormone administered toananimal, however
minute, eventhough theresidues maybebelow thelevelofdetection.
(iv) Therewasnowaytodistinguishmeatproducedusingthethreenaturalgrowthhormones
inaccordance withgood animal husbandry practice from other meat.
TheUnited States stated thatallofthisdemonstrated thattheECbanwasunscientific. Itwasbased
neither onscientific principles noronsufficient scientific evidence. Italsodemonstrated thatbanned
andunbanned meat were "like" products andtherefore thattheECbanwasinconsistent with
Articles III:4andI:1ofGATT.
5.37 TheUnited States alsoclaimed that,contrary totherequirements inArticle 5.1,theEuropean
Communities hadfailed tobaseitsbanonanassessment oftherisks. TheEuropean Communities
hadnever provided acopyofanyriskassessment thatcould serve asabasisforitsban.Itwasobvious
thattheEuropean Communities hadnotrelied onanyoftheopinions ofthescientists referred toby
theEuropean Communities during the17and18February 1997 meeting withtheexperts when it
implemented thebanthatbecame effective in1989, norwhen itpromulgated itsnewdirectives in1996
tobecome effective inJulyofthisyear. Indeed, theEuropean Communities apparently hadnotconsulted
anyofthese scientists untilitwaswellintoaWTO dispute settlement proceeding toreview itsban.
Bycontrast, thecompetent ECauthorities hadofficially determined that,contrary toaban,theCodex
standard wascorrect andnoMRL orADIwasnecessary.
5.38 TheUnited States observed thatthevarious presentations oftheoutside scientists during the
17-18 February 1997 meeting didnotinanymanner constitute ariskassessment. They weresimply
anattempt ataposthocrationalization oftheECbanandassuchwere irrelevant tothePanel’s
examination, inaccordance withitsterms ofreference, ofwhether theECbanwasbased onarisk
assessment. IftheECbanweretrulybased onariskassessment, onewould expect tofindarecord
ofthecompetent ECregulatory authorities expressing health concerns related toeachofthesubstances
atissue, commissioning laboratory testsorother studies, reviewing theresults ofthose studies and
reaching certain conclusions, andthentaking regulatory action. TheEuropean Communities had
presented nosuchrecord tothePanel. TheEuropean Communities didundertake ariskassessment
bytheLamming Committee, buttheresults ofthatriskassessment didnotsupport theECban. One
would alsohaveexpected anyriskassessment toinclude some determinations regarding exposure of
consumers tothesubstance. There wasnoevidence thattheresults oftheresidue testing described
bytheEuropean Communities were reviewed todetermine exposure levels.
5.39 According totheUnited States, contrary toArticle 3.3,theEuropean Communities hadfailed
toshow thatitsbanwasdesigned toachieve ahigher levelofprotection thantheCodex standard for
thehormones, which wasdesigned toresult in"noappreciable risk"fromexposure toresidues. The
European Communities never opposed thescientific consensus ontheCodex standards through seven
stages ofCodex review. Atthelaststage theEuropean Communities opposed adoption byCodex,
buteventhentheEuropean Communities never raised anyconcerns withthescientific justification
forthestandards. NorhadtheEuropean Communities everrequested JECFA toreview thestandards.
5.40 TheUnited States alsostated thattheECprofessed concern overpossible misuse didnotjustify
theECban. Even ifmisused, theresidues ofthesixhormones could wellbebelow theCodex or
FDA MRLs (inthecaseofthethree synthetic hormones) orwithin normal physiological ranges (in
thecaseofthethree natural hormones). Indeed, direct injection (rather thanuseofanimplant) of
doses 100times higher thanapproved doses stillresulted inresidues wellbelow theestablished ADI.
Furthermore theECbanwasnotsocarefully tailored soastoapply onlytoproducts derived from
improperly treated animals. Finally, iftheEuropean Communities wanted tosaythatitwasallright
tousethese hormones inaccordance withgood practice, butitwasnotallrighttomisuse them, then
theUnited States would support theEuropean Communities.WT/DS48/R/CAN
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5.41 TheUnited States didnotcondone misuse andoperated arigorous compliance programme
forthese hormones. TheUScontrol programme wascomparable totheECprogramme. TheEC
references tothenumber ofsamples tested intheUnited States presented aninaccurate picture. Residue
testing wasonlyonecomponent ofawell-designed control programme. IntheUnited States, theFDA
andtheFood Safety Inspection Service oftheUSDepartment ofAgriculture hadextensive compliance
programmes toensure thatanimal drugs wereusedsafely. Testing wasjustonepartofthiscompliance
programme. Thephilosophy oftheUSanimal drugcompliance programme wasthesame asthatof
other quality assurance programmes. Thatis,quality must bebuiltintoaproduct nottested intoa
product. Since theUnited States believed thatonecould nottestone’swayintocompliance, theUS
compliance programme involved various activities toensure thatanimal drugs were usedproperly.
These activities included:
(i) Surveillance ofsalesrecords todetermine where thedrugwasbeing soldandused.
(ii) Education, including teaching fieldinvestigators about foodsafety concerns thatwould
arisefollowing anymisuse ofanimal drugs.
(iii) On-site inspection. Field inspectors werenotonlypresent intheslaughter plants but
FDA inspectors hadon-farm authority thatincluded surveying allthedrugs usedon
thefarmandauditing records ofdruguse.
5.42 TheUnited States stated thattesting ofthefoodsupply forviolations waspartofthiscompliance
program. When residue violations werefound, aninspector followed uponthisviolation byvisiting
thefarmanddetermining whatdrugs werebeing used. Finally, theUnited States utilized various legal
actions including criminal prosecution ofproducers andveterinarians thatmisused animal drugs.
5.43 Withrespect tothe1986report ofmisplaced implants referred tobytheEC,theUnited States
explained thatin1986, theFDA didindeed identify aproblem withthemisplacement ofimplants.
The"misplacement" dealtlargely ifnotexclusively withplacement oftheimplant inthewrong part
oftheearofthecattle. FDA tookswift compliance action tocorrect thisproblem andtheproblem
hadnotoccurred since. Rather thanafailure oftheUSsystem, theUnited States believed theincident
demonstrated theeffectiveness oftheUSregulatory compliance system.
5.44 Withrespect totheECclaim thattheUnited States hadestablished ADIs forthethree natural
hormones, theUnited States explained thatithadnotestablished ADIs forthese threehormones. The
numbers referenced bytheEuropean Communities werenotADIs. They werenotlegallimits atall.
They wereabenchmark thatwasoneofseveral factors considered when deciding whether toapprove
aproduct. They werenotlegal, regulatory limits. Ifashipment ofmeatwere found thatexceeded
these figures, thiswould notitself beabasis forregulatory action.
5.45 TheUnited States alsocommented ontheresponses oftheexperts tothe18February 1997,
"Additional Questions ofthePanel totheExperts." TheUnited States firstnoted thatwhile onepossible
explanation ofthemechanism ofaction ofcarbadox wasthatitacted asananti-microbial toreduce
theamount offloraintheintestines, thishypothesis hadnotbeenconfirmed. Thegrowth promotion
effect ofcarbadox wasclear, butcarbadox wasnotessential foranimal health. Secondly, theconcept
thatonecould separate theadverse effects onhuman health, ifany,ofresidues ofendogenous hormones
fromthesame hormone supplied byanimplant waswithout scientific support andhadnobasisinfact.
Finally, itwastheUSbelief thatcompliance waseasier ifananimal drugwere legal. Legal use
permitted thecollection ofsales records, patterns ofuse,control ofmanufacturing procedures, and
education programs onsafeconditions ofuse. Similar compliance mechanisms were notavailable
forillegal products soldontheblack market. TheUnited States alsoobserved thatsince theEChad
explained thatallsixofthehormones werecovered bytheECresidue testing programmes, andthatWT/DS48/R/CAN
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ittested 200,000 samples, thenitwasclear thatresidue testing wasafeasible alternative totheEC
ban.
5.46 TheUnited States concluded bystating thatitwasimportant toputthiswhole dispute in
perspective. Itdidnotmake sense toexamine theissue ofresidues ofthese hormones from growth
promotion inisolation asthough thiswould betheonlyexposure forconsumers. Humans were all
constantly exposed tosignificant quantities ofhormones, bothduetoendogenous production andto
exposure from many foodsources. Humans allhadnatural mechanisms intheirbodies toregulate
thelevels andbalance ofhormones within asetrange, rather likeathermostat inahome regulated
thetemperature within arange. Inanygiven person, hormone levels varied overawiderange each
day. Humans wereconstantly exposed notjusttothese hormones, buttomany other hormones and
other substances aswell-chemicals produced endogenously intheirbodies andchemicals naturally
found infoods oradded tofoods. Indeed theamount ofhormones inmeat, regardless ofwhether the
meatwasfrom ananimal which hadbeenadministered hormones forgrowth promotion, wassmall
compared totheamount ofhormones insome other common foods, suchasmilk. Theresidues in
meatwereinconsequential compared tothenatural production inhumans. These residue levels were
nowhere nearenough todisrupt hormone levels orthehormone balance ineventhemost sensitive
members ofthepopulation.
VI. PANEL 'SCONSULTATION WITH SCIENTIFIC EXPERTS
6.1 Asregarded theselection procedures andcriteria, theEuropean Communities considered
thattheuseofexperts bythePanel forthepurposes ofscientific andtechnical advice should respect
general principles oflaw. Inparticular, itshould betransparent, avoid conflicts ofinterest, affirm
theintegrity ofthedispute settlement process andaidpublic confidence intheoutcome ofthedispute287.
Inaddition, Appendix 4oftheDSU included general rulesoflawrelating totheuseofexpert advice
onthepartofPanels. Eventhough theexperts would notconstitute anExpert Review Group butwould
beconsulted individually andseparately, suchrulesshould beapplied byanalogy whenever relevant
andappropriate288.Inorder toensure thattheprinciples outlined above wererespected, theEuropean
Communities believed thatanumber ofgeneral criteria should befollowed intheselection ofthe
scientific experts bythePanel.
6.2 TheEuropean Communities indicated that,first, theexperts nominated bythePanel should
notbenationals oftheparties tothedispute nornationals ofthirdparties inthesame dispute. This
principle aimed atensuring afairandimpartial selection ofexperts andappeared allthemore necessary
inlightofthepossibility given bythePanel totheparties tonominate oneexpert each, without any
limitation ofnationality. Second, thePanel, inselecting experts withdifferent fields ofexpertise, should
ensure thatalltheareas which ithadidentified were covered, sothatallthequestions ofthePanel
received replies tothefullest extent possible. Third, given theverysmall number ofexperts thatthe
Panel would consult, onlyscientists withproven expertise intheuseofhormones ingeneral andfor
animal growth promotion should beselected. Fourth, theexperts should nothaveserved asmembers
oftheCodex/JECFA group which produced the1988JECFA report ontheuseofhormones foranimal
growth promotion. Fifth, pastorpresent significant tieswiththeindustry producing these hormones
would notprovide sufficient guarantees oflackofconflict ofinterest, ofintegrity andofaiding public
confidence intheoutcome ofthedispute. TheEuropean Communities considered thattheabove
comments constituted compelling reasons fortheEuropean Communities andunderscored thelimited
poolproposedbytheCodexsecretariatfromwhichthePanelwouldmakeitschoice,despitetheexistence
287TheEuropean Communities noted thatinaletter addressed tothePanel on21October 1996, theUnited States had
alsoagreed tothese general principles.
288TheEuropean Communities noted thatthishadalsobeen acknowledged inthePanel 'sletter of30October 1996.WT/DS48/R/CAN
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ofalarge number ofscientific experts onthese issues internationally. TheEuropean Communities
indicated thatPanel'sfavorable response totheECrequest toaddafifthscientist withexpertise in
theareaofcarcinogenic effects ofhormones inthiscaseaddressed oneoftheconcerns oftheEuropean
Communities.
6.3 Asregarded thepurpose ofrequesting information from, andthetypeandnature ofthequestions
tobeasked to,experts, theEuropean Communities stated thatthisshould be"tofurther thePanel's
understanding ofthescientific factsrelevant tothedispute". Inorder tofulfil thisobjective andbe
inconformity withtheprovisions oftheSPSAgreement andtheDSU, thequestions thePanel intended
toaskmustrelate directly tothescientific issues ofthecase. These questions must beaddressed to
persons whoonthebasis oftheirrecognized fields ofexpertise, could provide direct, reliable and
verifiable information tothePanel. Thequestions should notconcern legal issues orissues of
interpretation ofanyoftheWTO Agreements under consideration, because itwasthesoleresponsibility
ofthePanel tointerpret thelegalprovisions which hadbeeninvoked bytheParties andtoapply them
tothefactsofthepresent case. TheEuropean Communities observed thatthequestions thePanel
intended toaskshould alsonotaddress norrequest purefactual information, which wastheresponsibility
oftheparties tothedispute toprovide, inaccordance withtheDSUrulesanditsprovisions onburden
ofproof. Theyshould notaddress issues oftradepolicy either, which wereagain thesoleresponsibility
oftheparties andonwhich scientists were notcompetent andcould notbeexpected topronounce
themselves. TheEuropean Communities claimed thatscientists mustbeasked onlyscientific questions
directly relevant tothisdispute andinthelightofthescientific arguments made bytheparties tothis
dispute. TheEuropean Communities recalled thatitwasthePanel'sresponsibility tointerpret and
apply therelevant legal provisions. Accordingly, theEuropean Communities considered necessary
tostress thatitreserved allitsrights withregard totheconformity ofthePanel'sapproach onthese
issues withtherelevant provisions oftheSPSAgreement andtheDSU.
Panel procedures withregard toscientific expertise
6.4 Following consultation withtheparties, thePanel decided toseekscientific andtechnical advice
asforeseen inparagraphs 1and2,firstsentence, ofArticle 13oftheDSU, andpursuant toparagraph 2,
firstsentence, ofArticle 11oftheSPSAgreement.
6.5 Names ofindividuals expert inthesubject matter before thePanel wereprovided bytheCodex
Commission secretariat aswellasbytheInternational Agency forResearch onCancer ("IARC").
Brief curricula vitaewere solicited from allexperts whowere prepared toassist thePanel.
6.6 ThePanel decided toseekadvice fromthesameexperts selected toadvise thepanel considering
aseparate complaint regarding thesame measure, thePanel onEuropean Communities -Measuring
Concerning Meat andMeat Products (Hormones) -established attherequest oftheUnited States.
Theparties tothatdispute hadbeenprovided theopportunity tocomment onthese potential experts
onthebasisofthecurricula vitae, andinparticular tostateanycompelling objections theymight have
withregard toanyindividual. Theparties hadbeeninvited tonominate oneexpert each, notnecessarily
fromthelistprovided bythePanel. ThePanel thanselected twoadditional individuals fromthelist
taking intoaccount thecomments oftheParties. Attherequest oftheEuropean Communities, the
Panel decided toselect anadditional expert intheareaofcarcinogenic effects ofhormones, onthe
understanding thattheEuropean Communities agreed thatthePanel established attherequest ofCanada
would seekadvice fromthesamefiveexperts. Canada wasinvited tocomment ontheexperts identified
bythetwoparties. These experts wererequested toserve, intheirpersonal capacities, asindividual
advisers tothePanel. ThePanel alsosought information from theCodex Commission secretariat.
6.7 ThePanel, inconsultation withtheparties, prepared specific questions which itsubmitted to
eachexpert individually. Theexperts wererequested toprovide theirresponses, inwriting, tothose
questions theyfeltqualified toaddress. TheParties agreed thattheirwritten submissions tothePanel,WT/DS48/R/CAN
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including thewritten versions oftheiroralstatements, beprovided toeachoftheselected experts.
Written questions werealsosubmitted totheCodex Commission secretariat. Thewritten responses
oftheexperts andoftheCodex Commission secretariat were provided totheparties.
6.8 Theexperts wereinvited tomeetwiththePanel andtheparties todiscuss theirwritten responses
tothequestions andtoprovide further information. Asummary oftheresponses provided bytheexperts
ispresented below.
6.9 Theexperts selected toadvise thePanel were:
Dr.Francois André, Laboratoire desdosages hormonaux, France
Dr.Dieter Arnold, Deputy Director, Federal Institute forHealth Protection ofConsumers
andVeterinary Medecine, Germany
Dr.George Lucier, Environmental Toxicology Programme, National Institute of
Environmental Health Sciences, United States
Dr.JockMcLean, University ofSwinburne, ProViceChancellor, Division ofScience,
Engineering andDesign, Swinburne University ofTechnology, Australia
Dr.LenRitter, Executive Director, Canadian Network ofToxocilogy Centres, University
ofGuelph, Canada
Dr.AlanRandell oftheCodex secretariat alsoadvised thePanel.
Views ofthescientific experts
Question 1:
Invarious JECFA andCodex references theterms "good animal husbandry practice", "good
veterinary practice" and"good veterinary andanimal husbandry practice" areused. Canyou
define "good animal husbandry practice", "good veterinary practice" and"good veterinary and
animal husbandry practice"? What aretheimplications, interms ofresidue levels andpotential
hazards tohuman oranimal health, ofnon-application of"good veterinary andanimal husbandry
practices" forfiveofthehormones indispute?
6.10 Dr.André responded thatthese concepts related toquality assurance systems, however they
were notprecisely described orstandardized, andtheuseofsome ofthese concepts wasnotyet
widespread. "Good animal husbandry practice" wasdescribed invarious ways, suchas"thestable
totable approach" which tookintoaccount theuseofveterinary drugs suchasinaHerd Health
Surveillance Programme (HHSP). Insucharecording system, farmers, veterinarians andother people
concerned withallaspects ofprimary production should cooperate toensure good animal husbandry
practice.
6.11 "Good veterinary practice" described eachcountry 'snational orprofessional guidelines orrules
which provided guarantees forprofessional activities. Theuseofveterinary drugs wascontrolled by
means ofaninternational code ofpractice oftheCodex Alimentarius which described theuseof
veterinary drugs, from thenecessity ofapertinent diagnosis toresidue management (respect of
withdrawal periods) inmeat-producing animals. Dr.André noted thatspecial attention should bepaid
totheprescription andtousing thecorrect dosage, siteandroute ofadministration formedicines.
Moreover, specific conditions fortheuseofparticular drugs wasregulated; ie.,inEurope, ECDirective
96/22 described precisely theconditions oftherapeutical orzootechnical useofthehormones indispute.WT/DS48/R/CAN
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6.12 Dr.André noted that"good veterinary andanimal husbandry practice" didnotappear tobe
welldefined butcould beconsidered asacombination ofthetwoabove-mentioned practices. The
strict observance of"good veterinary andanimal husbandry practice" wastheonlywaytoguarantee
thateachdrugwould beusedaccording totheconditions forwhich ithadbeenregistered. Any
disrespect ofsuchpractices, intermofdosage, injection route, withdrawal period orother conditions
specified foruse,would change theexpected levelofresidues. Concerning thehormones indispute,
itcould easily bedemonstrated thatoverdosage, shorter withdrawal periods (when defined), orliquid
solution injections instead ofimplants might leadtohigher residue levels. Potential hazards tohuman
andanimal health might thenappear.
6.13 Dr.André indicated thattherealproblem wasoneofcontrol: howtoensure thatthesepractices
werereally respected. There wereofficial control services charged withthiscontrol. Butnowmore
andmore veterinarians, farmers, andfarmer organizations weretaking thecontrol andwereensuring
thattheyonlyusedregistered drugs astheywere officially meant tobeused.
6.14 Dr.Arnold observed that"good animal husbandry practice" wasabroad termrelating tothe
proper management andhandling ofanimals. Particularly intensive production methods required good
management. Theterms management andhusbandry included, forexample, efforts toward improving
rateofgainandfeedefficiency andmanagement ofreproduction (e.g., hormonal control ofoestrus,
embryo transfer, treatment ofinfertility, prevention ofpregnancy, termination ofpregnancy, induction
ofparturition, etc.). Veterinarians were involved inthemanagement ofseveral ofthese conditions
andwereinteraliaresponsible thatcertain drugs wereonlyadministered afterthorough diagnosis and
incompliance withtheapproved labelinstructions. Itwasalsoafundamental requirement thatdrugs
(hormones, growth promoters, parasiticides andother substances) should notbeusedtoreplace good
veterinary andanimal husbandry practices.
6.15 Dr.Arnold indicated thatthehormones under discussions werenotpersehazardous orinnocent
substances. Ifingested withfood, theirpossible biological effects depended interaliaontheamounts
ingested. Therefore, itwasimportant thatduring theapproval process conditions ofusewereestablished
which guaranteed thatevenpreferential consumption offoodfrom treated animals would notleadto
theingestion ofresidues causing biological effects. Theessential issue wascompliance withthe
establishedconditionsofusewhichwerenormallylaiddowninthelabelinstructions.If"goodveterinary
andanimal husbandry practices" werenotapplied, inparticular if"good practices intheuseofveterinary
drugs" werenotobserved when using thesesubstances, residue levels higher thanthose resulting from
theauthorized conditions ofusemayoccur/were likely tooccur inedible portions ofthetreated animals.
These elevated levels didnotalways havebiological effects -because theestablished margins ofsafety
were usually high.
6.16 Dr.Lucier indicated thathehadlittleexpertise inthisarea,butitseemed reasonable toassume
thatnon-application ofsuchguidelines orinconsistent application ofthemwould substantially increase
thechance thatacceptable residue levels could beexceeded, which would likely increase thepotential
risktohuman health.
6.17 Dr.McLean responded that"good practice" wastheoperative partofthese definitions. The
word "veterinary" implied thataveterinarian wasinvolved intheprocess astheprescriber, advisor
oradministrator. "Animal husbandry" wascaring foranimals andmight involve aveterinarian inthe
process. "Good practice" inrelation totheuseofhormones involved theuseofaregistered product
according totheprescribed instructions foritsuseandemploying good farming practice. Itmight
alsoinclude theuseofapproved administration apparatus andtheidentification oftreated animals.WT/DS48/R/CAN
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6.18 Dr.McLean indicated thatdeparture from "good practice" wasundesirable andabreach of
theregistration conditions. However, inpractice, itwasunlikely thatminor departures from good
practice withregistered products would cause significant increases inhormone levels inmeat.
6.19 Dr.Ritter indicated thattheseterms hadbeenelaborated inarecommended international code
ofpractice (Codex Alimentarius, 1993) intended tofoster thesafeuseofveterinary drugs infood
producing animals andtoensure that,inaccordance withtheprinciples ofthiscode, residues of
veterinary drugs infooddidnotexceed permitted levels andresidues didnotposeahazard tohumans
consuming foodcommodities produced withtheaidofveterinary drugs. Inpractice, JECFA andCodex
hadnotutilized these terms, butrather hademployed theterm"good practice intheuseofveterinary
drugs", which hadbeendefined (Codex Alimentarius 1993) as"theofficial recommended orauthorized
usage including withdrawal periods, approved bynational authorities, ofveterinary drugs under practical
conditions. Themaximum residue limitforveterinary drugs maybereduced tobeconsistent with
goodpractice intheuseofveterinary drugs". Themaximum permitted residue wasbased onthetype
andamount ofresidue considered tobewithout toxicological hazard forhuman health while taking
intoaccount other relevant public health risks. When thehormones atissue wereusedinaccordance
withtheprescribed useconditions, thelevels thatwere present were infactindistinguishable from
those which would bepresent inananimal which hadnotbeentreated atall.
6.20 Dr.Ritter further noted thattheprinciple orphilosophy ofgoodveterinary andgoodhusbandry
practice alsoimplied thatallveterinary products tobeutilized infoodproducing animals should only
beadministered instrict compliance withrelevant product information, approved bytheappropriate
regulatory authority, andinstrict accordance withinstructions issued byqualified veterinarians.
Violations ofanyofthese principles might result inhigher thanexpected residues orresidues of
unexpected drugs. Theimplications ofsuchviolations wereproportional tothefrequency withwhich
theyoccurred, themagnitude oftheviolation andtheprevalence ofsuchviolations within thefood
production system. Notwithstanding, given theexaggerated estimates ofsafety inherent intheapproach
totheestablishment ofMRLs, itwasunlikely thatoccasional violations could increase overall residue
levels tothose which, onaninfrequent exposure basis, could posearisktoconsumers.
Question 2:
Canmeatproduced withanyofthesixhormones indispute forgrowth promotion purposes (natural
and/orsynthetic)bephysicallydifferentiated,byconsumersorbyanyparticulardetectionmethods,
from meat produced without them? Areresidues ofthethree natural hormones administered
forgrowth promotion purposes chemically different fromresidues ofthese hormones administered
forpurposes permitted bytheEC?
6.21 Dr.André noted thatnophysical differences wereobserved between meatproduced withor
without theuseofgrowth-promoting hormones, butquestions ofmeatquality could beraised asfar
asphysicochemical ororganoleptic criteria were concerned. Significant alteration ofeating quality
andlossoftenderness ofmeatproduced withvarious implants hadbeenreported. These changes might
alsostemfromdifferences inthechemical composition ofmeat. According tosexand/or implant type,
differences ofmoisture andfatrateswere observed.
6.22 Furthermore, sophisticated detection methods allowed differentiation ofmeatproduced with
orwithout synthetic hormones, evenifalongwithdrawal period wasrespected. Fornatural hormones,
thisdifferentiation waspossible when esters ofnatural hormones were stillpresent inthemeat. In
some cases itispossible todistinguish thetwobyphysical means ofisotope relations, butitwould
beverydifficult todoatverylowlevels, Theoretically, quantitative differences might beexpected
between thelegaluseofnatural hormones asgrowth promoters (i.e.asanimplant) andtheiruseas
veterinary drugs (i.e.usually asinjection); from thequalitative point ofview, chemical differencesWT/DS48/R/CAN
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could beexpected interms ofmetabolites and/or conjugates, owing tothedosage, theroute of
administration andthelength oftreatment.
6.23 Dr.Arnold responded thatitwasnotpossible tophysically differentiate meatfrom treated
animals frommeatofuntreated animals. However, many studies showed thatthecomposition ofthe
carcass wasimproved upontreatment interms ofmore leanmeatandlessfatthaninuntreated control
animals. Residues found inthemeatfrom treated animals forgrowth promotion purposes would be
qualitatively thesame asresidues found inmeatfrom animals treated withthesame substances for
purposespermittedbytheEuropeanCommunities,butquantitativelycouldbeslightlydifferentdepending
onthecompound administered, thedose, theroute ofadministration, etc.Ifthesubstances wereused
according togoodveterinary practices, therewasinitially aslight difference butatthetimeofslaughter
there wasnomeans todiscriminate between treated andnon-treated animals, irrespective ofwhether
forgrowth promotion orfortherapeutic andzootechnical purposes.
6.24 Ofthecategories ofresidues ofbiological concern, onlytheresidues oftheparent drug
administered totheanimals (e.g.thehormones itselforitsesters) could beanalytically differentiated
withcurrently available analytical methods. Theoretically, hormones could belabelled withstable
isotopes topermit discrimination between added hormones andendogenous hormones, butthishad
norelevance inpractice. Itwaspossible todiscriminate whether ornotanimals hadbeentreated with
exogenous hormones. Despite theirshorthalf-lives incirculation, itwasevenpossible, butnotnormally
routinely feasible, tomeasure theconcentrations oftheesters atsitesdistant from theinjection site.
6.25 Itappeared thatthesubstances usedforgrowth promotion intheUnited States were(with the
possible exception oftestosterone-propionate) alsousedintheEuropean Union fortherapeutic or
zootechnical purposes. Working-Group IIIofthe1995ECScientific Conference hadconcluded that:
"While residue analyses fornatural hormones onanimals treated experimentally canshow differences
between them anduntreated animals, itisnotpossible inroutine usetoidentify treated animals on
thebasis ofassays ofedible tissue samples anditisdifficult inblood, urine orfaeces. Successful
identification oftreated animals maybemade byanalysis ofinjection sitesordetection ofesters (e.g.
oestradiol benzoate) inblood shortly aftertreatment. Identification ofanimals treated withnatural
hormones onthebasis ofasingle time-point analysis isdifficult. Thesituation ismore complex for
food-producing animals, where typically amixture ofandrogen onlyisused. Identification ofmeat
from animals treated withnatural hormones andimported from third countries isnotatpresent
possible"289.(emphasis added)
6.26 Dr.Lucier indicated thattheresidues which occurred from thenatural hormones were
indistinguishable from those which occurred from thenatural endogenous materials. Thiswasnot
true,ofcourse, forthesynthetics. Withappropriate analytical methods andappropriate residue levels
onecould detect residues ofthesynthetic materials hereinquestion. Thehalflife,thebiological
persistence, oftheagents inquestion wasforthemostpartrather short; theydidnotstickaround the
body verylong. Half-life wasthetimeittakes forhalfthematerial todisappear. If,forexample,
something hadahalflifeofonedayand,ifyoustarted outwith10unitsofit,onedaylateryouwould
havefive,twodayslateryouwould havetwoandahalfandsoforth. Soeventhough several months
might elapse following anexposure toanagent evenwitharelatively short halflife,afewmolecules
might remain. Thenumber ofmolecules might beremarkably close tozero, probably notdetectable
byanalytical methods, butafewmolecules would likely remain. (Seealsoresponse toquestion 5).
6.27 Dr.Lucier noted thatitwaslikely that,ontheaverage, meatfromgrowth-promoted animals
would beleaner (i.e.lessfat)thanmeat produced without those agents. However, itwasunlikely
that,foragiven piece ofmeat, onecould physically differentiate whether ornotitwasfromagrowth-
289Working Group III,Detection andSurveillance, in1995 ECScientific Conference Proceedings, p.31.WT/DS48/R/CAN
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promoted animal. Residues arising fromadministration ofthethree natural hormones would notbe
chemically different from those inthebody ofnon-treated animals although theresidues werelikely
tobeslightly higher inthegrowth-promoted animals.
6.28 Dr.McLean responded thatforallpractical nutritional andhealth purposes themeatwasthe
same regardless ofhowitwasproduced, although there might bevariations intheratiooffattolean
meat. Theresidues ofthenatural hormones were generally similar when administered forgrowth
promotionorforotherpurposes.Becausethemodeofadministrationusedforgrowthpromotionresulted
inlower dailydosing, theremight bequantitative andqualitative variations inthecomposition residues.
6.29 Dr.Ritter observed thatitwasgenerally known thatwhen usedasgrowth promoters, the
naturally occurring gonadal steroid hormones -oestrogen, progesterone andtestosterone andtherelated
substances MGA, zeranol andtrenbolone, could increase thegrowth rate,theproportion ofleanmeat
tofatandfoodconversion efficiency insome species. Overall theresponse might varybetween
hormones, andmight bemaximized bytheuseofcertain combinations ofhormones. Ingeneral, the
leanmeatcontent ofthecarcass wasimproved andthefatcontent wasdecreased. Except inthecase
ofsome vealcalves, effects onmeatquality weregenerally notsignificant. Thus itwasmostunlikely
thatconsumers could differentiate physically between meatproduced withorwithout thesehormones.
JEFCA concluded thatitwould beverydifficult todetermine residue levels attributable totheexogenous
useofthenaturally occurring gonadal hormones.
6.30 While itwasmostunlikely thatconsumers could physically differentiate meatproduced with
synthetic hormones, residues could bereliably detected wellbelow those levels regarded assafe.
However, qualitatively theresidue would beindistinguishable. Quantitatively, theamount thatcould
bedetected would beafunction oftheamount thatwould havebeenadministered either forgrowth
promotion ortherapeutic uses.
Question 3:
Ifanyoneofthesixhormones oracombination thereof isadministered totheanimal, willthere
always bearesidue ofthathormone inthemeat ofthatanimal, evenifitissosmall thatitcannot
bedetected? Question 32:Further toquestion 3,could thehormone loadingested byhumans
from other foodstuffs (including endogenous hormones) begreater thanwhich occurs from the
consumption ofbeefderived from hormone-treated cattle?
6.31 Dr.André indicated thataspecific detection limitbelow which aresidue could notbeidentified
and/or quantified wasdefined foreachmethod. Itnever meant thattheresidue wasnotstillpresent
inagiven matrix. Thelower thedetection limitofthemethod, thelower thelevelofresidue which
could berevealed, butthelonger thetimeofpossible identification oftheresidue. Forsome growth
promoters thetimeduring which itwaspossible tofindresidues hadchanged from oneweek toone
month aftersubstantial improvement ofthemethod (high resolution massspectrometry instead oflow
resolution mass spectrometry forinstance). With thedevelopment ofsophisticated newmethods, it
waspossible toobserve residues remaining much longer thanwascommonly known.
6.32 Other foodstuffs thanmeat from hormone-treated cattle contained hormones, especially
oestrogens. Thiswasthecaseofoffals, ofcertain plants, ofmeatfromspecific animals (such aspregnant
cows); allcontained highlevels ofhormones. However, theconsumption ofthese foodstuffs was
always occasional andwould notenhance risks forhuman health. Thiswasnotcomparable tothe
systematic enhancement ofthehormonal content ofmeat.
6.33 Dr.Arnoldstatedthathewasnotconsideringtheendogenouslyproducedhormonesas"residues"
inhisanswer. Anyexogenously administered hormones present inthebodyoftreated animals should,
however, beconsidered as"residues", eveniftherewasnodifference instructure andbiological activityWT/DS48/R/CAN
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compared withtheendogenously produced hormones. Theuseoftheterm"residue" didnotimply
thatthese residues were potentially harmful tohuman health.
6.34 Whether animals were slaughtered without anywithdrawal timeorattheendofthelegally
established withdrawal time, therewould always bearesidue. Theexogenous compound wasnotabsent
attheendofthewithdrawal time; however, thesumofboththeendogenous andexogenous molecules
would beatorwithin physiological limits. Ifthepresence ofresidues were toberegulated onthe
basisof"no-detectable-residues" (which wasimpossible because theendogenous hormones alone were
already above thelimitofdetection), there would nonetheless bemore than1000 billions molecules
oftheadministered exogenous hormone present inonekilogramme ofmeatatthelimitofdetection.
Inother words, the"no-detectable- residue" concept wasafalse-zero-residue “concept. Foranyof
thesixhormones,itwasimpossibletoestimatethewithdrawaltimesrequiredtoreachtrue"zero-residue"
levels evenwiththeaidofthemost sensitive analytical methods.
6.35 Many foods ofbothplant andanimal origin contained natural hormonal substances insuch
amounts that,depending ontheactual diet,thedietary intake could belower, equal orhigher than
theamount ingested withbeeffrom hormone-treated cattle. Iftheendogenous production wastaken
together withthedietary intake, itwould always bemuch higher. Given theirnatural presence infood,
hestated thatonecannot escape eating these hormonally active substances, orsimilar substances with
related biological potential.
6.36 Dr.Lucier responded thatbiological half-life datawasavailable foreachofthese hormones,
soresidues could bereasonably predicted atvarious times afterexposure hadceased. Inthecaseof
zeranol thehalf-life wasapproximately oneday.Thus, ifasample contained 100ppbwhen exposure
ceased, 50ppbwould remain afteroneday,12ppbatthree days, three ppbatfivedaysandsoon.
Although thelevels afterseveral months would beextraordinarily small andverylikely non-detectable,
afewmolecules would remain.
6.37 Dr.McLean indicated thataminute residue, wellbelow anypresent method ofdetection, might
remain. Thiscould bepostulated fromaknowledge ofpharmacokinetics. Thisminute residue would
beofnosignificance when compared withendogenous production ofnatural hormones inthehuman
body, orthedietary intake ofnatural oestrogenic substances infoodorcontaminants which were
oestrogenic.
6.38 Dr.Ritter observed thatinthecaseofthenatural hormones, andinaccordance withappropriate
useprocedures, hormone levels could beexpected todecline tolevels thatwould beassociated with
untreated control animals. Because these hormones werenormally produced endogenously, itwould
beessentially impossible todistinguish these lowlevels asoriginating fromanexogenous source, and
inanycasethese levels fellwellwithin therange normally present inuntreated animals. Inthecase
ofthexenobiotic hormones, andinparticular trenbolone acetate andzeranol, residue levels ofthese
hormoneswouldnotnormallybeexpectedinuntreatedanimalsandhencecouldbedetectedinmonitoring
programmes. Itwaspossible that,depending onthewithdrawal period selected, some residues ofthe
xenobiotic hormones might remain, evenifbelow thelimits detectable byroutine methodology.
Question 4:
How dotheresidues from thethree synthetic hormones indispute differ, ingeneral, from those
ofthethree natural hormones indispute ifadministered inaccordance withgood husbandry
practice andgoodveterinary practice? And, inparticular, when usedforanimal growth promotion
inaccordance withgood husbandry practice and/or good veterinary practice? How doresidues
ofhormones naturally present inanimals, meat, meat products orhuman beings, differ from
those ofadditional hormones administered toanimals? Dothese differences, ifany,result in
different potential risks tohuman health?WT/DS48/R/CAN
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6.39 Dr.André replied thatbecause thecompounds were notthesame, theyledtochemically
differentresidues.Theresiduesalsodifferedquantitativelyaccordingtothedosage.Levelsofoestradiol,
testosterone andprogesterone residues increased significantly inanimal tissues aftertreatment, when
compared withcorresponding untreated animals. Usually, theincrease ofresidue levels wasmore
pronounced infatthaninmuscle andother edible tissues. Concerning trenbolone andzeranol the
approximate residue levels could beconsidered, forbothcompounds, tobeclose totheppblevel.
6.40 Differences between natural occurring hormones atanatural occurring level andthesame
hormones atahigher levelorsynthetic hormones (whatever theirlevelofresidue) resulted systematically
indifferent potential riskstohuman health, dueeither tothelevelofresidue orthenature oftheresidue
(metabolites). According totheroute ofadministration ofadditional hormones, some differences in
metabolites patterns might appear. Metabolites could bespecies-specific: metabolites notformed in
cows might forminhumans andresult inpotential risksforhuman health. Thepotential induced risk
could beduetothehormonal activity ofresidues. Thepotential adverse effect could alsobea
carcinogenic effect.
6.41 Within thephysiological range these hormones hadnodifferent biological effects onhuman
beings. Butifoneateonlymeatfrom treated animals, there would beaverysmall enhancement of
themean offoodhormonal intake andthiswould notbetransformed inclassical biological effects
forhuman beings. Theproblem wasthatsome other biological effects hadneeded tobestudied over
alongtime. Sucheffects included, forexample, changes inhuman fertility orchange inthesexratio,
whichwascurrentlychanginginsomecountries.Buttherewasnocurrentlyknownrelationshipbetween
these developments andthefactwhether these countries banned ornotthese hormones.
6.42 Dr.Arnold responded thatinchemical terms, there wasnodifference between endogenously
produced "natural hormones" andexogenously administered "nature-identical" hormones. There were,
however, clear chemical differences between the"natural" and"nature-identical" hormones onthe
onesideandthexenobiotic hormones ontheother side. Thexenobiotic hormones donotnaturally
occur inanimals, meat, meatproducts orhuman beings, soanyreliably detected residue ofthethree
synthetic (xenobiotic) hormones wasindicative ofatreatment oftheanimals. Iftheproducts were
administered inaccordance with the"good practices", such residues might frequently occur in
concentrations toolowtobedetectable inmeat.
6.43 Interms ofbiological activity, inprinciple, thepotential biological effects ofthe
"nature-identical" exogenous hormones were thesame asforthe"natural" endogenous hormones.
While theconcentrations ofendogenous hormones were, however, regulated depending one.g.,sex,
age,developmental stage etc.,theexogenous hormones could, inprinciple, beadded insuchamounts
astoeither gradually disturb or-athighdoses -evenoverwhelm theinternal regulatory mechanism.
Single highdoses (e.g., resulting from theingestion ofa"full" injection site)would normally cause
transient effects. Repeated highdoses (notreached through ingestion ofresidues resulting fromuses
suchasgrowth promotion, therapy, orzootechnical treatment) could significantly change thehormonal
balance oftheindividual.
6.44 Dr.Arnold summarized thatthepotential risks tohuman health arising from thehormonal
activity ofthexenobiotic hormones wasslightly different inquantitative terms. Thepotential risks
arising fromother thanhormonal actions werequalitatively different. These riskswereassessed during
thereview andapproval process, andtheapproved conditions ofuseeliminated allunacceptable risks.
6.45 Dr.Lucier replied thattheresidues from thethree synthetics differed inseveral ways from
thenaturally-occurring hormones. First, thechemical structure wasdifferent. Second, anymetabolite
orbreakdown products would likely bedifferent. Third, thesynthetic hormone, although mimicking
thenatural hormone, might haveadditional biological properties notfound inthenatural hormone.
These differences could possibly result indifferent potential riskstohuman health.WT/DS48/R/CAN
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6.46 Some biological effect could occur. Forexample, anormal woman might have30percent
ofheroestrogen receptors occupied atsome given point intime. Atthatsame point intime, ifshe
wasconsuming meatthatcontained anadditional burden ofoestrogens because oftheuseofgrowth
promoters, thatreceptor occupancy might besomething like30.01 or30.001, averyverysmall increase.
Thisincrease would notbedetectable, notevenclose tobeing detectable, byanyexperimental tools
available today. Thus, abiological effect could beoccurring; ifitwasoccurring itwould notbe
detectable; andfinally therelationship between thatbiological effect (receptor occupancy) andatoxic
effect, saycancer orbirth defect orsomething likethat,would beunknown. Butifsuchaneffect
were occurring, itwould beextraordinarily small, close tozero.
6.47 Dr.McLean indicated thattheresidues from thesynthetic hormones differed from those of
thenatural hormones because theywerechemically different compounds andtherefore theirmetabolites
would alsobedifferent. Inthecaseofthenaturally occurring hormones, theresidues inmeat and
humans would beverysimilar. Anydifference would notposeapotential risktohealth.
6.48 Inrelation tothenaturally occurring hormones, Dr.McLean noted thatitwasnotpossible
todifferentiate between theeffects ofmeatfromtreated animals against meatfromuntreated animals
because essentially theywereinthesame biological range. Inthecaseofthenon-naturally occurring
hormones, inestablishing theADIverysensitive endpoints werederived fromstudies innon-human
primates, andthenthesituation ofsensitive members ofthepopulation wastaken intoaccount when
establishing safety factors. Thelevels inmeatweresubstantially below those causing anyeffects in
primates, andtherewasareasonably goodcorrelation ineffects ofhormonal levels inprimates against
humans. Therefore thelevels present inmeatfromanimals thatweretreated withthetwonon-natural
growth promotants would notcause effects inhumans consuming themeat.
6.49 Dr.Ritter observed thatwhen introduced exogenously assubcutaneous implants, thenatural
hormones were absorbed andmetabolized inanidentical manner totheendogenous form thereby
producing aspectrum, bothqualitatively andquantitatively, ofresidues which wereindistinguishable
from thenormal endogenous hormones. Inthecaseofthesynthetic hormones, trenbolone acetate,
zeranol andMGA usedasgrowth promoters, tissue residues were notnormally present andhence
detectable residues were attributable totheir use. Inthiscase, maximum residue levels were
recommended onlyaftercareful andthorough evaluation ofthesafety file,foodconsumption factors,
selection ofappropriate withdrawal periods and,inconsideration thereof, residues remaining were
notconsidered toposearisktoconsumers ofmeatormeatproducts containing these residues ator
below internationally recommended limits.
Question 5:
TheEChasidentified certain potential health hazards ofconcern toit(ie.,carcinogenicity,
synergistic effects, genotoxic effects, long-term useandexposure tocombination ofthehormones
inquestion). Towhat extent were these hazards taken intoconsideration inthecontext ofthe
1988 JECFA report orintheestablishment oftheCodex standards forthehormones inissue?
Towhat extent dotheriskassessments referred tobytheECassess these suggested hazards?
Hadthesixhormones indispute beenusedasanimal growth-promoters overasufficient number
ofyears foranassessment ofthelong-term effects ofsuchhormones onhuman oranimal health
tobemade? Question 29:Further toquestion 5,towhat extent dotheADIs andMRLs established
byCodex foranyfoodadditive, pesticide, etc.,takeintoaccount theeffects onhuman health
ofexposures tomixtures ofveterinary drugs, orexposure tothehormones inquestion originated
byother sources? Towhat extent dotheADIs andMRLs established byCodex takeintoaccount
theeffects onhuman health ofexposure tomixtures ofveterinary drugs, orexposure tothe
hormones inquestion originated byother sources?WT/DS48/R/CAN
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6.50 Dr.André indicated thatthepotential health hazards taken intoaccount byJECFA werebased
ondataavailablein1988.Moreoveronlytoxicologicaleffectsofthesedrugswereevaluated.Synergistic
effects, longtermuseandcombination ofhormones werenotfullyevaluated. Newresults concerning
toxicological effects ofnatural andsynthetic hormones hadbeenpublished since 1990, mostofthem
in1995 and1996. Some ofthese newdataweretaken intoconsideration when preparing EC96/22
and96/23 Directives, however theywerenottaken intoaccount bythe1995ECScientific Conference
because thebibliography fortheConference hadbeenprepared atthebeginning of1995. Many other
hazards forhuman health could beeither scientifically proven orexcluded. Owing tothenature of
these hormones, theresidue levels, andthewaytheywere ingested (assuming thatgood veterinary
practice andgoodanimal husbandry practice wererespected), a30to50yearperiod might benecessary
toobtain substantial data(asfororalcontraceptives orasbestos inhalation).
6.51 When individual drugs wereusedincommon veterinary practice fortherapeutic purposes, the
probability ofthesimultaneous useoftwodrugs waslow; theprobability ofaninterference between
them waslower, andlower stillwastheprobability thatonecould influence theelimination rateof
another. Forthehormones usedasgrowth promoters, theproblem wasdifferent. They were used
onaverylarge scale. Many animals were treated sothattheprobability tohave simultaneous
administration ofother drugs andofthese hormones became much higher. Agood riskassessment
should takethisintoaccount, buthewasnotaware ofthathaving beendoneeither inthecountries
where these hormones were inuseorattheinternational level.
6.52 Dr.Arnold replied thatsynergistic (andantagonistic) interactions ofthese hormones atall
levels -fromthemolecular tohigher organisational levels -werekeyelements oftheirnormal biological
functions. Itwasdifficult toidentify whattheoretical hazards might arisefromtheoretically possible
maximal changes intheorder of<0.1percentofinternal hormone pools duetotheconsumption
ofmeat from animals treated withtheapproved hormonal growth promoters. Long-term exposure
tohormones inlaboratory animals andhumans wasfullycovered bytheJECFA evaluations (e.g.in
thecaseofzeranol andtrenbolone-acetate bythechronic/carcinogenicity studies reviewed). Datanot
available tothe32nd JECFA were completed atthe34thmeeting oftheCommittee.
6.53 IntheCommunity, thecompetent advisory body forthesafety evaluation ofoestradiol-17 ,
progesterone andtestosterone wastheCommittee forVeterinary Medicinal Products (CVMP), asection
oftheEuropean Medicines Evaluation Agency (EMEA). EMEA wasalso,inprinciple, thecompetent
authority forthereview ofapplications formarketing authorization ofveterinary medicinal products
usedforgrowth promotion. Acentralised review process would bemandatory under theprovisions
laiddown inRegulation 2309/93. Theuseofanyhormonal substance forgrowth promotion was,
however, currently prohibited.
6.54 UndertheprovisionsofArticles7and14ofCouncilRegulation2377/902290,MaximumResidue
Limits (MRLs) hadtobeestablished forthetherapeutic andzootechnical uses ofthethree
"nature-identical" substances before theendof1996. TheEMEA reviewed (inaccordance with
regulation 2377/90) thetherapeutic usesofoestradiol-17 incattle andhorses. Thepublic summary
report states:
"3.Toxicological effects found afteroestradiol administration comprise hyperplasia ofthe
endometrium,behaviouralchangesandeffectsofmetabolicprocesses.Oestradioldoesnotinduce
genemutations invitro,butconflicting results arefound inchromosomal aberration assays.
Following longtermexposure theincidence oftumours intissues withahighlevelofhormone
receptors isincreased (e.g.mammary tumours). Itisconcluded thatthetoxiceffects including
carcinogenicity occur asanextension ofthephysiological effects ofoestradiol ...
290Council Regulation (EEC) 2377/90, ECOfficial Journal L224/1 of18August 1990.WT/DS48/R/CAN
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7.Theconclusion oftheFAO/WHO Expert Committee onFood Additives (JECFA) thatno
ADIandMRLs foroestradiol needtobeestablished isadopted. Milkandplasma residue levels
aftertreatment withoestradiol benzoate andoestradiol valerate haveshown tobeatorwithin
physiological limits. Although itislikely thattissue residue levels willalsobewithin
physiological limits, thiscannot beguaranteed, given theresults with oestradiol
hexahydrobenzoate. Still, compared tothelowest human daily production rateofoestradiol
inprepubertal boys(6(µg/d)) andcompared totheamount ofoestradiol inother foodstuffs
thatarepartofthehuman diet,theamount ofexogenous oestradiol thathumans willbeexposed
tothrough ingestion oftissue from treated animals isbiologically insignificant, andwillbe
incapable ofexerting ahormonal effect inhuman beings".
6.55 EMEAalsoevaluatedprogesteroneinaccordancewithregulation2377/90.Thepublicsummary
report consists of17paragraphs andshows thatthefollowing aspects hadbeenconsidered bythe
Committee: natural occurrence, veterinary uses, target animal safety, biological effects, endogenous
production inhumans, normal levels infoodanimals andinfoodofanimal origin, pharmacokinetics
andmetabolism, acute andshort-term toxicity inlaboratory animals, reproductive toxicity,
teratogenicity/embryotoxicity,andlong-termeffectsincludingcarcinogenicity.TheevaluationbyJECFA
ofthissubstance wasalsoconsidered.
With respect tocarcinogenicity itwasstated:
"9.According totheInternational Agency forResearch onCancer (IARC), progesterone does
notexhibit mutagenic activity inmost invitroandinvivotestsperformed, butisknown to
increase thetumour incidence inendocrine target tissues (ovaries, uterus, mammae) after
continuous (parenteral) doses clearly above thephysiological levels. Progesterone isnot
carcinogenic perse,butactsviaanepigenetic mechanism associated withitsendocrine activity,
i.e.itsability tocause ahyperproliferative effect atcellular levels mediated bysteroid-hormone
receptor interaction. Hence, tumours willnotresult from ingestion ofprogesterone atlevels
thatdonotproduce anyhormonal effects".
Theevaluation process oftestosterone inaccordance withregulation 2377/90 wasstillongoing.
6.56 Sofarnocomplete riskassessment hadbeenconducted intheCommunity; themostcompetent
assessment wasmade bytheScientific Working Group onAnabolic Agents inAnimal Production
chaired byProfessor Lamming. ThisCommittee comprehensively reviewed theavailable scientific
evidence, including industry data,concerning fiveofthesubstances under dispute. Itsrecommendations
were endorsed bytheScientific Committee onAnimal Nutrition, theScientific Committee onFood
andtheScientific Veterinary Committee oftheEC.However, when theinterim report waspublished,
long-term toxicity dataonthexenobiotic substances wasavailable onlyfortrenbolone acetate. The
reportalsodoesnotmentionthat"synergisticeffects"andexposuretocombinationshadbeenconsidered.
The"Pimenta Committee" didnotitselfperform ascientific riskassessment butrather expressed views
onpublic perception ofscientific opinion, theroleofscience insociety, consumer preference, other
socio-economic factors andvarious aspects ofimplementation andcontrol ofaban.
6.57 The1995 ECScientific Conference hadnolegal mandate andtheSteering Committee was
entirely freetodesign theprogramme andtonominate invited participants. Alegalnotice inthereport
clarified thatneither theEuropean Commission noranyperson acting onbehalf oftheCommission
wasresponsible fortheusewhich might bemade oftheinformation. TheConference didnotassess
thehazards referred tobytheECinthisdispute. Withregard totheCodex process, Dr.Arnold noted
thatitwastruethattheEChadobjected tomove these MRLs tothenextstepintheprocedure, but
without raising anyhealth issues. TheEChadopposed because ithadspecific legislation prohibiting
theuseof,andconsumers didnotwishtoeatmeatfrom, treated animals.WT/DS48/R/CAN
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6.58 Sufficient timehadelapsed toallow anassessment ofthelong-term potential effects onthe
health ofthetarget animals. Iflong-term effects ofthese substances were tobestudied, theeffects
oftheendogenously produced amounts ofthesesubstances andoftheexogenously administered human
doses intherapy etc.were mostrelevant. Lifestyle andingestion asnormal foodconstituents could
alsobeimportant. Intheunlikely event thattheminute amounts added fromresidues would haveany
effect onhuman health, itwould notbepossible todiscover thiseffect against thisbackground.
6.59 Inresponse tothefollow-up questions (inparticular, question 29),Dr.Arnold noted thatthe
primary mode ofexposure tofoodadditives wasthrough ingestion ofthesubstance inthefoodsupply.
JECFA considered, where applicable, theoccurrence ofthesubstances asnormal body constituents;
thenatural occurrence infoods; exposure fromother uses; andinteractions withother foodadditives.
Forexample,whencanthaxanthinwasevaluated,theCommitteeconsideredalsotheusesofthissubstance
asfeedadditive inanimal nutrition andasanorally administered pigmenting agent forhuman skin
inbothpharmaceutical andcosmetic applications. Early initsdeliberations about safety margins the
Committee hadconcluded thatthemargin ofsafety should allow for,interalia,thepossibility of
synergistic action among foodadditives. TheADIforfoodadditives generally included thenatural
occurrence andthedeliberate addition tofoodofthesubstance. Testing of"mixtures" wasnotnormally
required. However, some foodadditives were bytheirverynature mixtures.
6.60 Withregard topesticides, testing of"mixtures" wasalsonotrequired, neither intheframework
oftheactivities oftheFAO/WHO Joint Meeting onPesticide Residues norinthelegislation ofthe
European Communities aslaiddown inDirective 91/414/EEC Annex II,PartA(O.J. L230pp.15-18).
6.61 Forveterinary drugs, testing of"mixtures" wasnotrequired. However, thecomprehensive
basic pharmacological screening required foralldrugs could provide information requiring further
follow-up inspecifically designed tests. JECFA hadevaluated anumber ofsubstances where theADI
wasbased onapharmacological NoObserved Effect Level. Thelegislation oftheEuropean Union
alsodidnotrequire testing of"mixtures" (seeDirective 92/18/EEC amending theAnnex to
Directive 81/852/EEC, O.J.L97of10April 1992, pp.1-23). However, therewasadifference between
"mixtures" andfixed combinations. Suchcombinations required justification onthebasisofadequate
testing. Repeated dosetoxicity testing could bemodified (i.e.reduced) incertain instances, forexample,
ifnewcombinations ofknown substances wereproposed andnopotentiating effects hadbeenobserved
during initial screening.
6.62 Dr.Arnold noted thattesting of"mixtures" ofhormones wasnotnormally required, unless
anunknown fixed combination wasadministered. Henoted thattheexperimental animals intoxicity
testing (orhumans, iftherewereusesinhuman therapy) weretypically exposed toallhormones existing
inthebody. Virtually allcellsweretargets ofoneorseveral oftheapproximately 50known hormones
andtheirmetabolites. Thesamehormone could haveseveral targets; thesame cellmight haveseveral
responses toasingle hormone. Thebattery oftestsincluded exposure atallstages ofdevelopment
from embryonic tofetaltoneonate toreproductive stateuntiltheendofthewhole lifespan, andthis
wayallsituations ofhormonal control werecovered. Thismeant alsothatallxenobiotic hormonally
active substances hadbeentested withrespect topossible interactions withthehormone system. No
specific toxicity testing hadbeenperformed withthefixed combinations authorized intheEuropean
Communities.
6.63 JECFA developed itsstrategies concerning theevaluation ofanabolic hormones inits25th
and26thReport. These indicated thatthetoxicological evaluation ofresidues ofanabolic agents that
arepresentinhumanfoodobtainedfromanimalstreatedwiththeseagentsmusttakeintoaccountwhether
theresidue wasidentical toahuman endocrine hormone. Inthelattercase,thepossible endocrinological
effects andcarcinogenic potential oftheresidue mustbeclosely examined. Inaddition, itwasnoted
thatchemically modified hormones, hormonally active agents fromplants, andsynthetic anabolic agents
presented thefollowing specific problems:WT/DS48/R/CAN
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(i) extreme potency andconsequently theneedtoensure minimal residues;
(ii) potential tumorigenic activity; and
(iii) thepresence oftheirmetabolites inanimal products thatmight beofendocrinological
ortoxicological consequence.
Theevaluation foracceptance oftheuseofxenobiotic anabolic agents inanimal foodproduction
resembled inmany respects theevaluation ofpesticides, sincethetwoessential elements required were:
(i) adequate, relevant toxicological data; and
(ii) comprehensive dataabout thekinds andlevels ofresidues when thesubstances are
usedinaccordance withgoodanimal husbandry practice, which required evidence as
totheefficacy oftheanabolic agent, theamounts usedtoproduce theeffect, theresidue
levels based onfieldtrials, andinformation about methods ofanalysis ofresidue levels
thatcould beusedforcontrol ormonitoring purposes.291
6.64 Dr.Lucier responded thattheissues ofcarcinogenicity, synergistic effects, genotoxic effects
andchronic exposure appeared tobeconsidered intheJECFA report, although thebasis forthe
evaluation (ADI recommendation) wasbased primarily onhormonal effects inmonkeys because the
othereffectsorissueswereconsideredoflessrelevancetohumanhealthrisks.Thehormonesinquestion
hadbeenusedlongenough togetinformation onwhether ornottheyposed animal health risks, provided
thatgoodrecords wereavailable. However, therewasnotractable approach fordetecting human health
risksfrom long-term useasthehealth risks, ifany,would bequite small.
6.65 Thenumber ofmolecules thatremain following appropriate useoftheseagents wasverysmall,
particularly inrelation totheamount ofnaturally occurring oestrogens orandrogens. Sothe
accompanying riskthatwould beassociated byconsuming meat containing residues would be
extraordinarily small. Itwould beveryhardonscientific grounds tosaythattheriskwaszero, but
itwaslikely tobevery, verysmall. Itcould bezero.
6.66 Interms ofthecarcinogenic activity ofthehormones inquestion, itwasalready known that
naturally occurring physiological levels ofandrogens andoestrogens werecarcinogenic. Therefore,
theissueofthreshold wasirrelevant tothetoxicological evaluation oftheseagents. Ifahundred thousand
molecules ofsomething already existinthebodyandsome ofthose molecules wereproducing aDNA
damage event, therewassome possibility thatthesame damage event would occur ifanother molecule
wasadded toitbecause itwasthesamemolecule. Itwould notbepossible todistinguish thatadditional
event from theonesthatoccurred from thethousand molecules. Butitwould notbepossible tosay
thatnoneofthose events wererelated tothatadditional onemolecule. Thiswould notbedetectable.
Thechances wereveryverysmall, butitwould beimpossible tosaythattheevent could notoccur.
6.67 With regard totheincreased incidence ofsome tumours occurring invarious countries inthe
world referred tobyDr.Epstein, itwasprobably truethattherewasarealincrease intesticular cancer
andthisincrease appeared tobepredominant inyoung menwhich wasespecially disturbing. Why
thiswasoccurring, noonereally knew itscause. There wasnoreason tothink, however, thatitwas
associated withoestrogen. There weremany other factors thatcould becausing that. Breast cancer
wasalsoontherise.However, onecould notnecessarily attribute thatincrease toexposure toexogenous
external oestrogens. There weremany reasons whyexposure togenotoxic agents could beaccounting
fortheriseinbreast cancer rates; oneneeded tobecognisant ofother factors andnotjustblame the
exogenous oestrogens foreverything. Regarding theoralcontraceptive issue, Dr.Lucier indicated
291Environmental Health Criteria 70,WHO, Geneva, 1987.WT/DS48/R/CAN
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thatDr.Epstein wasprobably rightthatthere would beanincrease inbreast cancer riskforwomen
whostarted taking thepillveryyoung because thatextended theperiod oftimeinwhich theywere
exposed tohighlevels ofoestrogen andthiswasaknown riskfactor forbreast cancer. Thesame
exposures alittlebitlaterprobably would nothaveanincrease, sowhen averaged out,there wasno
statistically significant increase inbreast cancer fromoralcontraceptives. Noonechallenged thefact
thatoestrogens were carcinogenic.
6.68 Withregard toDr.Metzler comments, Dr.Lucier noted thattheadducts thatmayarisefrom
synthetic materials werelikely different andofmore concern, interms ofariskassessment, thanthe
onesthatarisefrom thenaturally occurring ones, because there already wasagiven body burden of
thenaturallyoccurringoestrogens.Thequestionofgenotoxicornon-genotoxicwasessentiallyirrelevant
heresincethedoseresponserelationshipsforoestrogenincreasesincelldivision(onepossiblemechanism
ofcarcinogenesis)waslikelytobelinearbecausenormallevelsofoestrogenwerecausingcellreplication.
6.69 Dr.McLean replied thatthe1988 and1989 JECFA reports addressed theissues of
carcinogenicity andgenotoxicity andtheirfindings were accepted byCodex. Thecompounds were
notgenotoxiccarcinogensandtheresponsesseenwererelatedtotheirhormonaleffects.Thesehormonal
effects were evaluated using sensitive end-points innon-human primates. Inthecaseofsynergistic
effects, itwasrecognized thatthelevels resulting fromtreatment withthenaturally occurring hormones
were significantly lessthanthenatural levels already present inthetreated animals. Inaddition, it
mustberecognized thatallthree hormones occurred inmaleandfemale animals andhumans. With
regard tomutagenicity, dataforthenaturally occurring substances wasreviewed andreferenced in
theJECFA 1988 Report. Thereport wasnotsilent onthematter butitreferred tomutagenicity data
thatwasinthepublished literature. Inthecaseofprogesterone, testosterone andoestradiol-17 ,there
wereanumber ofpublished documents thatJECFA didlookat,andtheyarereferenced initsreport.
6.70 There wasalsohuman dataavailable fromtherapy withvarious natural andsynthetic hormones.
Thistherapy wascontinued inhumans formany years andtheriskshavebeenevaluated. Thelevels
found inmeataftertreatment aremany orders ofmagnitude lower thantherapeutic levels, arepoorly
absorbed orally andsodonotrepresent ahazard. Thecompounds hadbeenusedinmany countries
forlongperiods oftimeandthere wasnohuman epidemiological datawhich suggests anyhazard.
With regard toDr.Epstein 'sobservations related toincreasing numbers oftumours, Dr.McLean
observedthattheincreaseintumoursoccurredalsointhosecountrieswheretheuseofgrowthpromotants
wasnotwidespread andtheincrease began before thehormonal growth promotants received widespread
use.
6.71 Dr.Ritter noted thatdatarelating tocarcinogenicity andgenotoxicity wereindeed available
totheJoint FAO/WHO Expert Committee onatleastfiveofthesixhormones under discussion (all
butMGA). Inallofthese cases, therelevant dataformed thebasis of:(i)thesafety evaluation, (ii)
thedecision bytheCommittee thatanADIneednotbeallocated forthenatural hormones, and(iii)
theestablishment ofbothanADIandMRL’sfortrenbolone acetate andzeranol.
6.72 Withrelation tooestradiol, progesterone andtestosterone, JECFA concluded thattheincreased
tumour incidence wasattributed tothehormonal activity ofthese hormones associated withthevery
highdoses utilized intheexperiment. These effects werenotconsidered relevant toanevaluation of
thesafety offoodresidues. TheReport wassilent ontheresults ofmutagenicity studies, which were
available totheCommittee forreview. Withrelation totrenbolone acetate, JECFA similarly concluded
thatthecarcinogenic effects detected wereadirect consequence ofthehormonal effect associated with
thehighdoses utilized inthestudy andnotofdirest relevance totheinterpretation ofthesafety of
thefoodresidues. JECFA alsoconcluded thatthetumorigenic effect ofzeranol wasassociated with
itsoestrogenic properties atthehighdoses utilized inthecancer study, andtherefore asafeexposure
leveltohumans could bedetermined.WT/DS48/R/CAN
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6.73 Theissueofpotential synergy wasaddressed, atleastinpart,byJECFA through theconduct
ofbiochemical studies directed attheeffect ofexcretion ofhormone combinations when compared
tosingle hormones alone. Although these studies didnotspecifically address issues related toaltered
toxicity duetosynergy, these limited datadidprovide evidence thatwhile administration ofhormone
combinations could beexpected toalterexcretion kinetics quantitatively, there wasnoevidence of
important qualitative changes. Itwas,however, clear thatdefinitive studies relating togenotoxicity
orcarcinogenicity ofhormone combinations hadnotbeencarried out,eventhough thiswasfrequently
thepreferred method ofuse.
6.74 Dr.Ritter observed thattheuseofgonadal typehormones asanabolic agents hadbeenin
agriculturalpracticeforapproximately40yearsthroughmanypartsoftheworld.Regardingthesynthetic
hormones, bothzeranol andMGA hadbeenusedasanabolic drugs, atleastintheUnited States, for
approximately thirty years while trenbolone acetate hadbeeninuseforapproximately tenyears. At
leastinthecaseofthenatural hormones andbothzeranol andMGA, broad scale usehadnowbeen
inplace formore thanageneration withonlyfewandisolated reports ofpotential adverse effects.
Theprimary potential concern withregards tohuman health effects hadbeenthatofcarcinogenicity.
While theuseofthegrowth promoting hormones forperiods aslongas40years should havebeen
sufficient toresult inanincreased cancer riskinthehuman population, anincrease which could be
attributable totheuseofthese hormones hadnotbecome apparent. Noting thatbothbreast cancer,
particularly inpost-menopausal people, andprostatic cancer hadincreased sharply inaffluent countries.
Dr.Ritterpointedoutthatthisincreasewasthoughttobeprimarilyassociatedwithgeneticpredisposition
andsignificant alterations inlifestyle (Houghton andRitter, 1995).
6.75 Dr.A.Randell commented ontherelationship between theAcceptable Daily Intake (ADI)
andtheMaximum Residue Limit (MRL) andwhether ornotthese weremeasures ofacceptable risk.
Themaximum residue limitwasdefinitely notahealth-based limit. Itwasalimitestablished forthe
control ofveterinary drugs inactual practice. Theestablishment ofamaximum residue limitwassuch
thatthemaximum residue would never leadtoresidues which would, inanormal ingestion ofthe
product, cause anyconsumer toexceed theacceptable daily intake. Therefore there wasanupper
boundary tothemaximum residue limitimposed bytoxicology considerations. Thelower limitwas
normally derived from residue trials inpractice according totheproposed good veterinary practices
intheuseofthese drugs. However, inthecaseofzeranol, thislimitfellsofarbelow notonlythe
toxicologicallyderivedlimitbutalsothelimitthatonecoulddeterminewithnormalmethodsofanalytical
chemistry, thatitwasincreased totakeintoaccount thefactthatifadecent control programme were
notgoing tobeoverly expensive, thanthelimitmustbecontrollable byanalytical procedures rather
thanbyresidue trials. Theacceptable daily intake itself alsowasnotadirect riskassessment inthe
sense thatitprovided astatement ofquantitative risk. TheADIconcept stated thatthere would be
noappreciable riskasaresult ofexposure tothechemicals concerned. Thiswastruewithin theJECFA
andJMPR framework, forfoodadditives, residues ofveterinary drugs andpesticide residues. (Dr.
Lucier 'scomment thattheriskwasprobably somewhere between zeroandoneinamillion, provided
some sortofquantitative framework, butJECFA hadnever established aquantitative evaluation of
riskintheapplication oftheADI.)
Question 6:
Isthere anymore recent scientific evidence available withrespect totheeffects onhuman oranimal
health oftheuseofanyofthesixhormones indispute especially when usedforgrowth promotion
purposes, other than theevidence already taken intoaccount byCodex? How reliable are
extrapolations from animal studies topossible adverse effects inhumans? Further toquestions
6and8,areyouaware ofnewscientific evidence showing thatthecarcinogenicity, synergistic
effects, genotoxic effects, long-term useand/or exposure tocombinations ofthehormones in
question andtheir metabolites, ifanydonotonlydepend onthehormonal activity ofthedose
administered? Would suchevidence invalidate theADIs andMRLs established byJECFA/Codex?WT/DS48/R/CAN
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6.76 Dr.André noted thatrecent reports oftheeffects onanimal health from theuseofthesix
hormones indispute asgrowth promoters confirmed andfinalized previous results.292Based on
anatomical orhistopathological observations, these results demonstrated theeffects ofcommercially
available implants onanimal behaviour, development andreproduction. Young bullbehavioural
modifications hadbeenconfirmed: young bullstreated withzeranol "spent more timeidling, eating
andruminating thancontrols".293Animal libido wassystematically altered. Thechanges inthe
behaviour ofbullswereusually correlated withhistopathological modifications, welldescribed inthe
1980s asatoolfortreatment diagnosis andmore recently confirmed inbulls.294Similar phenomenon
hadbeenrecently studied inother species, astheeffect oftrenbolone inmalepigs.295Theinfluence
ofthese hormones usedasgrowth promoters onreproductive tractdevelopment andreproduction had
beenconfirmed inbeefheifers: "Thelower pregnancy rateinzeranol implanted heifers 100daysafter
exposure tobullswascaused byfailure tocycle early inlifeand,inthose thatwere cycling, failure
toconceive andabortions between 25and45daysofgestation".296
6.77 Firstresults ofrecent research work withmiceontheeffects ofhormones onanimal sexual
development andreproduction were published in1995. They concluded that"DES andZeranol
administered during midpregnancy leads todecrease fetalweight andsizeandlower numbers ofmale
offspring atbirth".297In1996, thesame authors demonstrated "thatprenatal exposure tozeranol or
DESinduced abnormal testicular differentiation inthemouse".
6.78 Concerning human health ,there wasadiscussion onthedecrease ofhuman sperm counts298,
anapparent increase oftheincidence ofhormonally-mediated diseases likebreast cancer and
endometriosis, andadecrease inthemale/female ratio, which were thought tobeduetooestrogens
intheenvironment. Whether theuseofhormones forgrowth promotion wascontributing tothiscould
notbescientifically proven atthepresent time.
6.79 Extrapolations from animal tohuman wasanofficial toolfortoxicological andefficiency
evaluation ofdrugs under development. Ingeneral, theywereregarded asconservative evenifthey
didalways contain acertain levelofuncertainty. Moreover, these testsonanimal models didnottake
intoaccountthemultipleexposuretomanydifferentcompounds(characteristicforhumandiet).Humans
weresometimes more sensitive foracertain effect thananimals, andtheywerenotalways inasgood
health aslaboratory animals. Theaction offoodprocessing onresidues wasnotchecked inanimal
experiments. Forsome effects ofchemicals onhumans, suchaslongtermeffects overgenerations,
noanimal models existed. Inother cases, results onanimal models havesometimes beenconsidered
asnotrepresentative. Forthese reasons, many drugs which hadbeenfullyvalidated inanimal models
hadbeenbanned afterseveral years ofuseinhumans andthediscovery ofanunknown hazard.
6.80 Dr.Arnold indicated thatsincethelast(JECFA) evaluation, science hadmade further progress
inseveral areas, including themolecular mechanisms ofaction andtheepidemiology ofcancer. The
newly available information didnot,however, substantially change thebasisfortheevaluation ofthe
292Renaville etal.(1987), Dehaan etal.(1990), Moran etal.(1988), (1990), Herenda (1987), Bealetal.(1988).
293Legoshin etal.(1994).
294Tipirdamaz 1991, Ciftci (1990).
295Lopez-Bote etal.(1994).
296King etal.(1995).
297Perez-Martinez etal.
298Nimrod andBenson (1996).WT/DS48/R/CAN
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fivesubstances bytheCodex/ JECFA system. Although animal studies, ingeneral, could provide
useful information onpossible adverse effects onhuman health resulting from exposure tochemical
substances, thepossible health effects resulting from theoralingestion oftrace amounts ofresidues
ofthethree nature-identical hormones, (oestradiol-17 progesterone andtestosterone) could notbe
reliably andquantitatively predicted from theinformation contained inavailable studies.
6.81 Earlystudiesinmice,whichwereconductedbetween1940and1973,andwhichwerereferenced
intheIARC Monographs, were innowaydesigned toassess thehuman cancer riskresulting from
oralingestion oflowdoses ofoestradiol-17 .None ofthese studies usedtheoralroute ofexposure
inanyanimal species. None ofthem wasconducted under GLP-like conditions oraccording to
contemporary testguidelines. Many ofthemwerepoorly documented. Theprincipal aimofthesestudies
wastoexperimentally produce tumours under avariety ofcondition. Thetestsubstance wasusually
subcutaneously administered (frequently asimplant). Thedoses were often extremely highandnot
infrequently caused ahighnumber ofearly deaths. Suchdosing wasinadequate forcarcinogen testing
inrelation tothesafety evaluation ofresidues. Thestudies demonstrated thatsubcutaneous injection
orimplantation ofhighdoses ofoestradiol-17 orofitsesters alone orinthepresence ofother
carcinogenic factors resulted inincreased incidence ofmammary, pituitary, uterine, cervical, vaginal,
lymphoid andinterstitial-cell tumours inmice. TheIARC working group concluded onthebasisof
allanimal datathattherewassufficient evidence forthecarcinogenicity ofoestradiol-17 inexperimental
animals.
6.82 Similarly theanimal studies withprogesterone which werereviewed byIARC werealsolimited
tosubcutaneous andintramuscular injections andsubcutaneous implantations ofhighdoses; inrats
andrabbits itwasalways given incombination withothersexhormones. Progesterone wasadministered
together with carcinogenic substances such asdimethylbenzanthracene, methylcholanthrene,
diethylstilboestrol orN-2-fluorenyl-diacetamide inthemajority ofthestudies reviewed. From these
studies IARC concluded: "There islimited evidence forthecarcinogenicity ofprogesterone in
experimental animals. Intheabsence ofepidemiological data,noevaluation ofthecarcinogenicity of
progesterone tohumans canbemade."
6.83 Similarly totheother twonature-identical steroid hormones, testosterone anditsesters were
tested inexperimental animals bysubcutaneous injection and/or implantation, andinrabbits by
intramuscular injection. InthiscaseIARC concluded: "There issufficient evidence forthe
carcinogenicity oftestosterone inexperimental animals. Intheabsence ofadequate datainhumans,
itisreasonable, forpractical purposes, toregard testosterone asifitpresented acarcinogenic riskto
humans. Theonlyrelated datainhumans, although insufficient foranevaluation, concern thepossible
long-term effects ofandrogenic anabolic-steroids."
6.84 Thecontribution ofinformation obtained fromthese animal studies wasoflittlerelevance for
thequantitative assessment ofthepotential effects onhuman health oforally ingested, verylowresidual
amounts ofthese substances having noeffects onthephysiological hormonal balance. Inparticular
noadditional human cancer riskcould bededuced from these animal studies intheabsence ofother
relevant information. With reference tostudies conducted byother scientists, namely Dr.Liehr and
Dr.Cavalieri regarding different types ofDNA damage orgenotoxicity established foroestrogen, Dr.
Arnold agreed thatwithchemical methods allthesethings could beproduced. Thequestion waswhether
itoccurred inliving cells, atwhat concentrations, what enzymes were involved, what wasthe
compartmentalization ofthese enzymes, etc.Inhisview, there weremany gapsintheevidence. A
scientist could notexclude thatattheendsomebody might show thatoestrogens acted directly onthe
gene. Forthemoment, theevidence wasnotconvincing anddidnotinvalidate thebasic conclusions
ofJECFA 1988.WT/DS48/R/CAN
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6.85 Inresponse tothefollow-up questions, Dr.Arnold indicated thathormonal activity wasa
necessary requirement ofhormonal carcinogenesis caused bythesubstances indispute. Hewasnot
aware ofanyevidence which would invalidate theADIs andMRLs established byJECFA/Codex.
6.86 Dr.Lucier indicated thatanimal datawereusually relevant forestimating human health risks,
particularly forhazard identification, andthere wasasubstantial body ofknowledge andpastrecord
tosubstantiate thisconclusion. However, itshould bekeptinmindthatthereisconsiderable uncertainty
inextrapolating highdoseanimal datatolowdosehuman risks. Over thelast5-10years much had
beenlearned about (i)themechanisms whereby hormones triggered responses intarget cellsincluding
theinterplay orcross talkbetween receptor systems, (ii)thedevelopment ofcredible approaches for
dose-response evaluation, (iii)thespectrum oftoxic effects produced byhormonally-active agents,
and(iv)theroleofmetabolic activation ofhormones. There wasagrowing body ofknowledge that
some hormones could beconverted togenotoxic metabolites. However, itwasnotclearwhether these
metabolites areinvolved inthecarcinogenic process.
6.87 Dr.McLean responded thathedidnotbelieve thatdatadeveloped after1989 would justify
arevision ofthepresent useofhormones forgrowth promotion. Forexample, studies ofinvitro
receptor binding assays inthepresence ofpesticides hadnotproduced evidence ofconcern. The
extrapolation inthecaseofthehormones wasarguably more reliable thanwithanyother class of
compounds because theirmode ofaction andtheirmetabolism wassimilar inbothanimals andhumans.
Non-human primate andhuman datawasalsoavailable inmany cases. Inthecaseoftrenbolone and
zeranol, theusual safety factors forinter- andintra-species variation were stillapplied. The
extrapolations from animal studies tohumans wasreliable inthiscase. Thecurrent ADIandMRL
would onlybeinvalidated ifnewdataestablished alower NOEL. Inthecaseoftrenbolone andzeranol,
theNOEL usedwasconservative andtherefore low.Inanyevent, ifanynational bodyorgroup believed
thatitwastimeforre-evaluation ofsome ofthehormones previously evaluated byJECFA itshould
approach theJECFA ashadbeendone onanumber ofoccasions withthenumber ofcompound of
varying chemical classes.
6.88 Dr.Ritter observed thattheJECFA review, andthesubsequent decisions byCodex, were
basedlargelyonreviewsconductedapproximatelyadecadeago.Inrespectofthethreenaturalhormones
(oestradiol, progesterone andtestosterone), the1995 ECScientific Conference generally recognized
thatthese substances could increase thegrowth rate,theproperties ofleanmeattofatandthefeed
conversion efficiency ofsomespecies ofanimals. TheConference re-affirmed thattheresulting residues
inmeatwere within thenormal physiological range andconcluded thattheconditions ofuseofthe
natural growth promoting hormones provided areasonable safeguard ofpublic health. Inrespect of
thesynthetic hormones utilized forgrowth promotion (trenbolone andzeranol), the1995ECConference
advanced theview thatatdoses required forgrowth promotion, residue levels ofthese xenobiotic
hormones were wellbelow thelevels regarded assafe. TheConference alsonoted theavailability
ofonlylimited dataonpossible adverse effects intarget animals andemphasized theneedforfurther
study oftheeffects ofgrowth promoters administered incombination, asthepresence ofonemight
alterthemetabolism oftheother.
6.89 Thevalidity ofextrapolations from animal studies tohumans wasthepre-eminent issue in
contemporary toxicological hazard andriskassessment andwasthebasisofthehazard evaluation for
drugs, pesticides, foodadditives andothercontaminants worldwide. Given thereliance bybothnational
regulatory authorities andinternational agencies onanimal studies forpredicting possible adverse effects
inhumans, itwould seem defacto thattheinternational scientific community hadplaced agreat deal
offaithinthevalidity ofthese extrapolations. Atthesame time, however, itwasalsoclearthatthe
validity ofanimal models inpredicting adverse human effects wasinfluenced bymany factors including
selection oftheappropriate animal model, doseselection, duration androute ofexposure andselection
ofappropriate riskmodels designed toestimate human risksresulting fromtheuseofasubstance under
realistic andpractical useconditions.WT/DS48/R/CAN
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6.90 Recognizing theinherent limitations ofanypredictive model, Dr.Ritter indicated thatthe
scientific community hadelaborated ahazard andriskassessment paradigm thatinvolved evaluation
ofabroad range oftoxicological endpoints, selection ofthemostsensitive fordetermination ofaNOEL,
application ofanadditional uncertainty factor forderivation ofanADIandmodels forestimation of
dietary exposure which invariably substantially exaggerated intake levels. Theneteffect ofthisseries
ofoverly conservative calculations wasmost likely veryconservative estimates ofrisk,intended to
compensate atleast inpart, forthelimitations inherent inthereliability ofanimal tohuman
extrapolations. Indeed, initsconcluding commentary, theSteering Committee ofthe1995ECScientific
Conference noted thatthenature ofthecalculations described above wassuchthatadherence tothe
ADIprovided ahighdegree ofconfidence thatadverse effects would notbecome apparent inpeople.
Inother words theEuropean Conference essentially reaffirmed andstrengthened theearlier conclusions
reached byJECFA thatinaccordance withoperating procedures thatwereprovided fortheuseofthese
substances, theirusedidnotconstitute arisktoconsumers offoodcommodities produced withthe
hormones atquestion, atleastforfiveofthesixsubstances.
6.91 Dr.Ritter noted thatDr.Liehr'swork andthework ofmany investigators wastoproduce
aneffect. Thiswastothemost fundamental issue inpharmacology andintoxicology, theconcept
ofdoseresponse. Dr.Liehr wasveryinterested inunderstanding theinduction ofcancer asaresult
ofexposure tothese hormones. Therefore, hisprotocol would necessarily bedesigned insuchaway
soastoproduce thedesired effect, inhiscasethetumour. Theintent inthecaseoffoodresidues,
wasobviously toavoid adoselevelwhich might constitute ahuman risk. Therefore, thelevels that
werepresent asresidues infoodwerethousands orhundreds ofthousands ormillions oftimes lower
thantheywould beinanexperiment which wasspecifically designed toinduce atumour. These two
experiments werecompletely atcross purposes witheachother; theywerefromtheirveryinitiation
intendedtoproduceentirelydifferentresults.Tocompareaprotocolwhichhadbeendesignedtoproduce
atumour toafoodresidue theusepractice ofwhich wassetupinsuchawaysoastominimize the
presence oftheresidue, wasarelatively meaningless comparison. Moreover, noonecould reasonably
assure thatthepresence ofthese residues albeit atlowlevels constitutes zerorisk;infactscientifically
itwould beimpossible toevertesttoacertainty. Butthepointwasthatiftheselowlevels didconstitute
arisk,theyconstituted ariskofamagnitude which approached zero.
Question 7:
Isthere anyscientific evidence available which demonstrates thatapotential foradverse effects
onhuman oranimal health arises from theadministration ofanyofthesixhormones indispute,
ingeneral, andinparticular foranimal growth-promotion purposes, ifadministered inaccordance
withgood animal husbandry practice and/or good veterinary practice?
6.92 Dr.André replied thatthere wasnopublished scientific evidence thattheadministration, in
accordance withgood animal husbandry practice and/or good veterinary practice, ofanyofthesix
hormones indispute ingeneral (i.e.fortherapeutical andzootechnical purposes) andinparticular for
animal growth promotion purposes, induced adverse effects onhuman health. Thisonlymeant that
during thelastdecades, incountries where theyareinuseeither forgrowth promotion purposes or
fortherapeutical andzootechnical purposes, noneoftheheath problems which could beduetotheir
use(such ascancers, reproduction problems ...)hadbeenscientifically related totheiruse.However
thequestions remained whether thishadbeenstudied andwhether theperiod ofusewaslongenough
(seeresponse toquestion 5above). Concerning animal health, seeresponse toquestion 6above.
6.93 Dr.Arnold indicated thathewasnotaware oftheexistence ofsuchevidence.
6.94 Dr.Lucierrespondedthat,tohisknowledge,therewasnopieceofscientificevidencetoindicate
thatanyofthesixhormones inquestion hadunequivocally caused adverse effects inhumans whenWT/DS48/R/CAN
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administered andusedproperly. However, therewassome information available which raised concern
foraslight effect onincidence ofhuman disease (seeresponse toquestion 8).
6.95 Dr.McLean stated thattheredidnotappear tobeanyevidence which unequivocally established
thatadverse effects hadbeencaused inanimals treated withhormonal growth promotants orinhumans
consuming meatfrom treated animals.
6.96 Dr.Ritter observed thatasearly as1982, aWHO appointed Working Group concluded that
when thenatural sexhormones were usedinaccordance withinstructions fortheiruseingrowth
promotion, suchusewould notpresent anyharmful effects toconsumers ofproducts which hadbeen
produced withtheaidofthesepromoters. ThisWorking Group alsoconcluded thatthelevels ofzeranol
andtrenbolone, andtheirmajor metabolites, found inedible tissue following appropriate useasgrowth
promoters, weresubstantially below thehormonally effective doses inanimal testsystems anddidnot
present ariskofharm tohumans. Overall, theWorking Group concluded thatthefivecompounds
weresafeforuseintarget animals andinsubsequent consumers when theywere usedasprescribed
forgrowth promotion inmeatproduction.
6.97 TheEC1995 Scientific Conference concluded thattheeffects onanimals interms ofdisease
incidence, performance, general mobility andmeat producing efficiency were either unchanged or
improved. Theeffects onanimal welfare werenegligible interms ofhealth, performance andeffects
onbehaviour, although itwasnoted thatthere might beatransient increase insexual activity for2-10
daysinsome adult steers receiving oestradiol.
Question 8:
Isthere anyscientific evidence available thatresidues ofanyofthesixhormones indispute could
have carcinogenic effects, eventhough inthecaseofthetwosynthetic hormones these residues
fallwithin theMRL levels established bytheCodex? Isthere anyscientific evidence concerning
thebiochemical andphysiological mechanisms bywhich thehormones subject tothisdispute exert
their carcinogenic effects? Please describe therelationship between thehormonal effect andthe
toxiceffect ofthesixhormones. Isthere athreshold levelbelow which there isnoscientific evidence
thatresidues ofthehormones would have adverse health effects onhumans? Aretheconcepts
of"Acceptable Daily Intake" and"Maximum Residue Level" valid for,orapplicable to,genotoxic
carcinogens?
6.98 Dr.André indicated thatprevious results onthecarcinogenesis ofhormones hadrecently been
confirmed. Thiswastrueforsingle hormones aswellasformixtures ofhormones, administered in
vivoandinvitro.Concerning themechanism bywhich thehormones exerted theircarcinogenic effects,
themost important model wasoestradiol-17 itself. Ithadbeenproven thatoestradiol-17 ,which
wasinvolved inthedevelopment ofbreast cancer, stimulated thedevelopment ofmalignant cells. Recent
results showed thatoestradiol-17 enhanced genomic instability inmalignant cells, inducing deletions
oradditions inDNA. Itwasreported thatnatural oestrogens (mainly oestradiol) induced cell
transformation viaoverexpression andsynthesis ofoncoproteins. Some newinformation about the
potential roleandmechanism ofaction ofprogesterone inbreast cancer induction andabout the
biochemical aspects ofpituitary oestrogen induced carcinogenesis werepublished; however, theydid
notdemonstrate achieved molecular induction process.
6.99 Recent dataonthemechanism ofthecarcinogenic effects ofhormones ledtotheconclusion
thathormones ortheirmetabolites exerted adirect effect ontumour initiation byDNA damage; for
oestrogen-dependent tumours, catechol oestrogens andtheirquinone forms would appear tobeinvolved.
Further, hormones stimulated thegrowth oftumours intissues inwhich theyhadspecific receptors.
They hadacomplex carcinogenic andgenotoxic effect. Thehormonal effect stemmed fromreceptor
binding, translocation tothenucleus andgeneactivation. Powerful oestrogens werestrongly boundedWT/DS48/R/CAN
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andconcentrated inthenucleus. Iftheirhydroxylation andoxidation induced potential genotoxicity
andcarcinogenicity, itwasnotsurprising thatthemore hormonally efficient theywere, themore
genetoxic andcarcinogen theycould be.
6.100 Dr.André concluded thathormones hadtobeconsidered asgenotoxic compounds andfor
suchcarcinogens, nothreshold levelcould bedefined; noADIandconsequently noMRL could be
established. Thiswasthegeneral opinion oftoxicologists (Kuiper, EC1995 Scientific Conference).
Thisopinion hadalsobeenadopted bytheUnited States Environment Protection Agency (EPA) for
acarcinogenic nongenotoxic dioxin, TCDD.
6.101 Dr.Arnold responded thatthere wasnoevidence available showing thatresidues ofanyof
thesixhormones indispute could havecarcinogenic effects, eventhough inthecaseofthetwosynthetic
hormones these residues fellwithin theMRL levels established bytheCodex. Itwasnotpossible to
summarise briefly alltheknown factspublished inthousands ofpapers inthelastdecades andin
particular inthepast5-20years.
6.102 Steroid hormones primarily influence theexpression ofgenetic information atthelevel of
transcription bybinding to,andactivating, transcription factors. Theactivated transcription factors
interact withtheregulatory orpromoter region ofthegenes. Thehormone receptors arethese
transcription factors inthecaseofe.g.,steroid andthyroid hormones. Thecomplete DNA sequence
ofthehuman oestrogen receptor wascloned forthefirsttimein1986using thebreast cancer cellline
MCF-7. Inthemean time, thegenomic genes forallthreereceptors (oestrogens (ER), progestins (PR)
and androgens (AR)) had been cloned. Dr.Arnold characterized the biochemical
hormone-receptor-interactions asfollows: receptors werepresent inlowconcentrations; theirbinding
siteswere saturable atphysiological concentrations. Thebinding sitesexhibited highspecificity and
highbinding affinity; binding wasreversible. Specific receptor binding wastheinitial andnecessary
stepinthesequence ofevents leading toahormonal effect although itwasnottheonlyreaction the
hormones could undergo. Theeffects terminated upondissociation ofthehormone-receptor complex.
6.103 Theinvolvement ofreceptors inhormonal signal transduction wasthusexplained bythefact
thatinaddition totherecognition domain forthehormone theypossessed asecond functional domain
(about 70amino acidslong) through which theycould bindtoDNA. Steroid-hormone-regulated genes
hadatleasttwodifferent regulatory elements, a"generic" promoter element and(a)hormone response
element(s) (itwasnotclearhowmany response elements actually existed innaturally occurring genes).
Itbound thehormone-receptor complex more avidly than thesurrounding DNA did. The
hormone-receptor might alsoregulate several genes inthesame cellanddifferent genes indifferent
target cells. Metabolites andrelated exogenous synthetic hormones might work onadifferent setof
response elements. Thedetails ofhowtheinteraction withDNA promoted transcription wasstillan
areaofinvestigation. However, thebasic principle waswellestablished.
6.104 Carcinogenesis could beoperationally described asamultistage process involving atleastthree
stages: initiation, promotion andprogression. Theintermediate stage ofpromotion didnotappear
toinvolve structural alteration ofthegenome ofthecellbutrather depended onaltered geneexpression.
Bothoestrogens andandrogens hadbeenshown tobeeffective promoters intheirtarget cellsaswell
asinliver. Incontrast toinitiation, promotion wasareversible stage depending oncontinued
administration ofthepromoting agent. Besides tissue specificity, thegeneral characteristics ofhormonal
carcinogenicity were: longinduction periods andprolonged exposure athighlevels withconcomitant
severe derangements inhomeostasis. Thedose-response relationship ofpromoting agents (aswellas
thereceptor-hormone binding) exhibited sigmoidal curves withanobservable threshold andamaximal
effect.
6.105 Hormonal carcinogenesis inexperimental animals hadmainly beenstudied inrats,miceand
hamsters. Thepromotor model ofhormonal carcinogenesis hadbeendeveloped through studies ofWT/DS48/R/CAN
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avariety oftissues ofthese animals. Thequestion under dispute wasnotwhether these models were
stillvalid butrather whether genotoxic mechanisms could additionally exist orwould need tobe
considered inorder tofully explain thecarcinogenic potential ofhormones. Inarecent review
("Molecular Mechanisms ofOestrogen Carcinogenesis", J.D.Yager andJ.G.Liehr, Annual Review
ofPharmacology andToxicology 1996, Vol.36,pp.203-32) itwasconfirmed thatthehormonal effects
ofoestrogens were necessary butnotsufficient toinduce tumours. Onemetabolite ofoestradiol
(16-Hydroxyoestrone) wasclaimed tobecapable ofbinding toDNA invitrobutthiscould notbe
confirmed invivo(unpublished observations byoneoftheauthors). Itwasfurthermore postulated that
thecatechol-oestrogen formed byhydroxylation inposition 4oftheA-ring ofthemolecule could be
involved inthegeneration ofreactive oxygen species through redox cycling. Catecholoestrogens were
alsoabletobindtoDNA invitro,afinding which wasnotconfirmed invivo.
6.106 Dr.Arnold further responded thataccording tocurrent scientific knowledge, threshold levels
below which residues ofthehormones hadnoadverse health effects didexistforagiven individual.
Theindividual threshold levels varied andthishastobeconsidered when setting exposure limits for
theentire population.
6.107 Dr.Arnold indicated thattheADIwasderived from a"NoObserved Effect Level" (NOEL)
using appropriate safety factors. While itdidnotitself represent athreshold dose, itwasindirectly
related toanotprecisely known threshold dose. Therefore, theADIconcept asdefined byJECFA
could notbeapplied inorder toestablish anexposure limitfordirect-acting genotoxic carcinogens
forwhich, atleasttheoretically, nothreshold dosecould exist. MRLs could beestablished, inprinciple,
toregulategenotoxiccarcinogens.Basicallythereexistedtwopossibilities:iftheresiduesweregenotoxic
carcinogens, alternative models, e.g.,riskextrapolation, could beusedtofindanMRL; inthecase
ofcarbadox, JECFA wasunable toallocate anADIbecause theparent drugwasconsidered tobea
genotoxic carcinogen. Inthiscase, however, theresidues weredemonstrably notcarcinogenic under
approved conditions ofuse.Thus, anMRL could beestablished onthebasisofregulating aninnocuous
metabolite.
6.108 Dr.Arnold noted thatMRLs primarily facilitated fairinternational tradeandwerenotdirectly
related tohealth effects. Only thetotaldietary intake oftheresidues ofconcern, taking intoaccount
allMRLs established forthesame substance andallrelevant commodities andtheirconsumption by
thepopulation, could becompared withanexposure limit.
6.109 Dr.Lucierrespondedthatinthecaseofthenaturallyoccurringhormones,particularlyoestradiol-
17andtestosterone, there wasverygoodevidence thatphysiological levels werecarcinogenic. For
example, breast cancer would strike oneinninewomen intheUnited States overtheirlifetime and
therewascompelling evidence thatphysiological levels ofoestradiol-17 werenecessary forthiseffect.
Theevidence came from bothanimal experiments andhuman studies andwasderived from alarge
baseofpeer-reviewed published information. Inthecaseofoestrogen, early menarche andlate
menopause increased riskwhereas ovariectomy wasprotective. Also, endometrial cancer was
dramatically increased byoestrogen replacement therapy ifunopposed byprogesterone. Inthecase
ofbreast cancer, consumption ofbeefwithelevated levels ofoestradiol-17 could increase riskslightly
ifthecarcinogenic riskwasnotalready saturated byphysiological levels ofoestrogen. Thequestion
ofthreshold wasirrelevant. Itwasknown thatexisting levels were already carcinogenic.
6.110 However, Dr.Lucier noted thatevaluation ofcarcinogenic riskinpeople consuming meatfrom
growth-promoted animals wascomplex. Forexample, progesterone might protect against endometrial
cancer. From adifferent perspective, oneknew thatdietwasacritical determinant ofbreast cancer
riskandthatfatinthedietwasariskfactor. Therefore, consumption ofmeat containing residues
ofgrowth-promoting agents might actually decrease riskbecause thatmeatcontained lessfatthanmeat
fromnon-growth promoted animals. Onbalance, breast cancer andprostate cancer riskcould possiblyWT/DS48/R/CAN
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bedecreasedbyeatingmeatfromgrowth-promotedanimals.Moreover,exogenousoestrogensprotected
against osteoporosis andcardiovascular disease.
6.111 Dr.Lucier indicated thatsimple categorization ofagents asgenotoxic ornon-genotoxic, alone,
hadlittle value indetermining ifanADIapproach oralinear approach wasmore valid forrisk
assessment. Thisopinion wassupported byanalysis of500cancer bioassays conducted bytheNational
Toxicology Programme (NTP).
6.112 Dr.McLean replied there wasnoevidence thattheresidues hadanycarcinogenic effect.
Inthecaseofthetwosynthetic hormones which hadaMRL, thiswasbased onaNOEL derived from
ahormonal end-point innon-human primates. There wasdataavailable which gaveinformation on
themechanism bywhich hormones influence theoccurrence oftumours inanimals andhumans. This
wasaveryactive fieldofresearch because oftheimportance oftumours ofvarious organs, suchas
thebreast ortheprostate. Natural andsynthetic hormones exerted theireffects bybinding tocell
receptors andcausing aseries ofbiochemical events which influenced themetabolism ofthetarget
tissues. Inaddition, cellproliferation and/or turnover might beinfluenced. Ifthelevelofhormone
wasbelow thatrequired tocause these events, there would benoadverse effects. However, inthe
caseofthenatural hormonal growth promoters, thenormal levels ofhormones inthehuman body
werealready many times greater thanthose fromresidues infood. Thesmall amount inmeatwould
notinfluence thecourse ofevents andtherefore would notaffect human health. Indeed itwasvery
difficult todetermine exactly where ourhormone burden came from. Butthefactofthematter was
thathumans wereconstantly being exposed toverysignificant levels ofhormones andthattheincidence
oftumours which wereassociated withhormones inhumans suchas,forexample, thebreast orthe
prostate, hadnotsignificantly increased since thesurveying hadbeencarried out.
6.113 Dr.Ritter noted thatcarcinogenicity datahadbeenavailable andreviewed forthethreenatural
hormones andforbothtrenbolone andzeranol (seeresponse toquestion 5).Theissue ofincreased
tumour production withallfivehormones wastherefore more amatter oftheoretical consideration
thanoneofpractical risk. Aswasthecasewithoestradiol, andindeed withtheother hormones under
consideration, tumour induction associated withhighexposure tothesesubstances wasamanifestation
oftissues withhighlevels ofspecific hormone receptors thatwerenormally responsive tostimulation
bytheparticularhormone(JECFA,1988).Theseeffects,whentheyoccurred,weregenerallyconsidered
tobetheexpression ofveryhighdosereceptor stimulation andwerenotbelieved tohaveanyparticular
relevance fortheevaluation ofrisksassociated withdietary exposure toresidues atmuch lower levels.
6.114 Itwasalsowidely recognized thattoxiceffects which might typically manifest atconsiderably
lower levels thenthose required forreceptor stimulation andattendant tumorigenic effects wereamore
appropriate basis forevaluation ofpotential adverse effects inhumans following exposure todietary
residues. Notwithstanding, someauthors (Liehr, 1996, unpublished; Adlercreutz, unpublished; Arnold,
etal.,1996) hadrecently advanced alternative hypotheses regarding metabolism andmechanism of
action ofthegonadal hormones.
6.115 Historically, forchemicals which displayed carcinogenic properties inlaboratory animals, it
wasassumed thatathreshold dosedidnotexist. Thisview wasdue,inlarge part,tothefactthat
earlystudies focused onverypotent carcinogens which manifested theireffect bydirect covalent binding
toDNA; agents ofthistypewhich acted through direct covalent binding toDNA hadalsoreferred
toasgenotoxic. Thesubsequent hypothesis argued thatevenasingle molecule ofasubstance might
cause aheritable change intheDNA structure which would ultimately leadtotumour formation. In
practice, itwasnowrecognized thatsuch ascenario wasnotlikely, andthatinanycasemany
carcinogens actedthrough anon-genotoxic mechanism andhence didnottarget cellular macromolecules
suchasDNA. Thisparticular point hadbeenextensively elaborated withtrenbolone, which wasthe
subject ofelaborate studies which demonstrated theabsence ofcovalent binding potential associated
withthishormone (JECFA, 1988). Itwasnowapparent thatNOELs could bedetermined formanyWT/DS48/R/CAN
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chemicals thatmayshow some evidence ofcarcinogenicity under experimental conditions. Under
conditions where theeffect wasclearly non-genotoxic itmight bepossible toderive NOELs, establish
anADIandpropose anMRL. Chemicals which produced carcinogenicity through acleargenotoxic
mechanism should beregulated asifathreshold dosecould notbederived andhence aNOEL, ADI
andMRL could notbeproposed. Inthecaseofnon-genotoxic carcinogens, there waslittlescientific
validity tothebelief thatthesechemicals should betreated orregulated differently thanchemicals which
produced other adverse effects through non-genotoxic pathways.
6.116 Dr.Ritter concluded thatthere wasnocompelling evidence tosuggest thatthese compounds
should beimmediately re-evaluated, onthebasis notonlyofthehistorical reviews which hadbeen
carried outbyJECFA andother organizations, butalsoonmuch more recent reviews, including those
published asaresult oftheEuropean Conference onGrowth Promotion inlate1995, early 1996, and
indeed onthebasis ofthestatements presented byDr.Liehr, Dr.Metzler andothers. Dr.Liehr's
recent work andthework which others recently citedsuggested thatthere werecircumstances under
which adverse effects could bedemonstrated inassociation withamultitude ofthese compounds.
However, scientists were compelled tolookatthetotality oftheevidence asitwasavailable. In
Dr.Ritter 'sview, thetotality ofevidence, recognizing theinformation presented byDr.Liehr and
other scientists, aswellasthehistorical information, suggested thattheassessments thatwereprovided
inJECFA 1988continued toassure areasonable degree ofsafety toconsumers ofthese commodities.
Thiswasnotonlyhisopinion, hestressed, butindeed alsotheconsensus conclusion ofthe1995 EC
Scientific Conference.
Question 9:
Isthere scientific evidence ofparticular human health effects incountries where meat produced
withtheuseofanyofthesixhormones indispute forgrowth promotion purposes isallowed for
consumption ascompared tohealth effects incountries where theuseofsuch hormones is
forbidden?
6.117 Dr.André indicated thatthere wasnoknown scientific evidence ofsuchparticular health
problems.Onlyserious,longtermepidemiologicalstudiescouldgiveinformativedata(seealsoresponse
toquestion 5).Furthermore, thecausal relation could bedifficult toidentify, i.e.ifcomparisons between
human health disorders wasbetween theUnited States population andtheCommunity population, there
were somany differences inlifestylebetween thetwocontinents, thattheprobability toprove the
responsibility ofonecausal factor (likehormones) would beverylow.However, acorrelation between
breast cancer incidence andblood oestrogen levels intheNorth American andJapanese populations
wasdemonstrated. Other markers ofparticular human health effects could beprostatic cancer, human
fecondity orsexratios.
6.118 Dr.Arnold replied thatnosuchevidence existed. Such comparisons could probably notbe
made because other factors, suchasgenetic differences ofpopulations, lifestyle differences, differences
intherapeutic usesofsome ofthesubstances andnumerous other factors, would havemuch greater
influence ontheincidence ofpossible health problems.
6.119 Dr.Lucier stated thathedidnotbelieve thatgeographical patterns ofhuman disease offered
anapproach fordetermining ifresidues ofgrowth-promoting agents inmeatincreased riskofthose
diseases.
6.120 Dr.McLean noted thathewasnotaware ofanyevidence thattherewasanydifference between
thehealth ofhumans incountries where hormonal growth promoters wereusedandinthose countries
where theywerenotused. Thelife-span ofhumans incountries where hormonal growth promotants
wereusedhadsteadily increased foranumber ofyears. However, thereported incidence ofcancerWT/DS48/R/CAN
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hadincreased because thepopulation wasolder, diagnostic capacity hadimproved andbetter nutritional
status increased cancer rates.
6.121 Dr.Ritter indicated thathewasunaware ofanydataorother evidence ofadverse human health
effects incountries where meatwasproduced withtheaidofthehormones inquestion, when compared
tocountries where thehormones were notutilized formeatproduction.
Question 10:
Howdothepotential adverse effects onhuman health from residues infoodingeneral, andmeat
inparticular, from pesticides administered inaccordance withgoodagricultural practice compare
withpotential adverse effects from residues ofthesixhormones inquestion, when themeat is
fromanimals towhich havebeenadministered thesehormones forgrowth-promotion inaccordance
withgood animal husbandry practice and/or good veterinary practice?
6.122 Dr.André noted thatthese parameters were notdeveloped withtheaimofcomparing the
potential health riskofcompounds. Each compound withpotential adverse effects onhuman health
wassubmittedtoindividualevaluations,soastodeterminespecificADIsandMRLs(infoodofconcern).
Withregards topesticides, Dr.André pointed outthatsome ofthepesticides might facilitate adverse
effects ofoestrogens onhuman health.
6.123 Dr.Arnold responded thatpesticides hadbiocidal properties andwerefrequently alsootherwise
verypotent chemicals. Certain groups ofpesticides were alsoused asveterinary drugs, e.g.as
ectoparasiticides. These substances might haveasignificant potential toharm human health ifnotused
according togood agricultural practices. TheMRLs established intheEUandelsewhere provided
sufficient consumer protection. Itappeared thatthemargin ofsafety applied when establishing Codex
MRLs forresidues ofveterinary drugs might besomewhat higher ifthefoodbaskets usedandthe
calculated Theoretical Maximum Daily Intakes (TMDIs) were compared. JECFA/JMPR and
CRVDF/CCPR hadstarted harmonising MRLs forsubstances which were usedinbothagriculture
andanimal production.
6.124 Dr.Lucier replied thatthetoolsofriskassessment werenotsufficiently accurate todetermine
ifpesticide residues orresidues ofanti-microbial agents posed agreater riskthanresidues ofgrowth
promoting agents. Ineachcase, theriskwassomewhere between zeroandasmall number.
6.125 Dr.McLean observed thattherehavebeenveryfewdocumented casesofadverse effects caused
bypesticide residues infood, when theywereadministered inaccordance with"good practice". There
didnotappear tobeanyproven cases linked tohormonal growth promotants. Theuseoftheword
"potential" implied hypothetical cases. Given thathormones hadeffects onsexual characteristics and
metabolic processes, thenpotentially thesewould change, ifthechanges could beperceived ordetected.
6.126 Dr.Ritter indicated thatMRLs neednotbeestablished forthenatural hormones, when used
inaccordance withgood veterinary and/or agricultural practice (seeresponse toquestion 5).Inthe
caseofthesynthetic hormones, thenature ofthestudies used toestablish their safety, andthe
methodologicalapproachfortheestablishmentofMRLs,includingdeterminationofaNOEL,calculation
ofanADI, establishing awithdrawal period andproposing MRLs, wasvirtually identical forboth
pesticide residues andhormone residues. Asaresult, onewould notexpect thatpotential adverse effects
onhuman health would belesser orgreater forhormone residues thanmight bethecaseforpesticide
residues.WT/DS48/R/CAN
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Question 11:
How dothepotential adverse effects onhuman health from residues ofcarbadox (used inswine
production) differ from thepotential adverse effects arising from residues ofthesixhormones
inquestion when usedforgrowth-promotion inaccordance withgood animal husbandry practice
and/or goodveterinary practice? Question 30:Further toquestion 11and26,would youconsider
thatthepotential adverse effects onhuman health and/oranimal health from residues ofcarbadox,
monensin, olaquindox, avoparcin, benzylpenicillin, carazolol, ivermectin andorganophosphorous
compoundsarecomparabletothepotentialadverseeffectsarisingfromresiduesofthesixhormones
atissue when used forgrowth-promotion inaccordance withgood animal husbandry practice
and/orgood veterinary practice? Areanyoftheabove mentioned substances carcinogenic? If
anyoneofthese substances oracombination thereof isadministered totheanimal, would there
always bearesidue ofthatsubstance inthemeat ofthatanimal, evenifitissosmall thatitcannot
bedetected?
6.127 Dr.André indicated thatcarbadox proved tobeagenotoxic compound, andconsequently no
ADIvalue hadbeenproposed byJECFA (seealsoresponse toquestion 10).Olaquindox wasknown
tobecarcinogenic. Dr.André wasnotfamiliar withtheothers.
6.128 Dr.Arnold noted thataslongasthe"good practices" wereobserved, there wasnorelevant
difference. Ifthelengthy withdrawal timewasnotobserved inthecaseofcarbadox, potentially
genotoxic carcinogenic residues oftheparent drugandanother carcinogenic metabolite were likely
tobepresent inmeatoftreated animals. Inthecaseofthehormones, onlythefrequent consumption
ofinjection sitesorimplants would potentially cause effects onhuman health.
6.129 Olaquindox wasgenotoxic inanumber oftests. However theparent drugwasextensively
metabolised andwasnotpresent asaresidue if"good practices" wereapplied. Ivermectin wasextremely
potent against parasites, butitwassafely usedinhumans forthetreatment ofe.g."river blindness"
atmuch higher thanresidue levels. Carazolol wasahazardous substance forhumans withchronic
bronchitiswhichwasasubstantialpartofthegeneralpopulation.Inaddition,carazololwasadministered
tothetarget animals byinjection. Benzylpenicillin wasabsolutely harmless forthegeneral population
butcould provoke allergic reactions insome sensitized people evenattheleveloftheMRL. Avoparcin
wasnotregistered asfeedadditive ontheAmerican continent; itsuseintheEUhadrecently been
withdrawn. Strict adherence totheidentified "good practices" wasanabsolute requirement forthe
useofsome ofthesesubstances. Nearly allofthesesubstances leftdetectable residues inmeatoftreated
animals under conditions of"good practice intheuseofveterinary drugs". Attheoralhearing
Dr.Arnold added thatthereisacommercially available alternative forcarbadox mainly oxytetracycline.
6.130 Dr.Lucier indicated thatitwasdifficult toaccurately compare risksfromcarbadox residues
torisksfromresidues ofgrowth-promoting substances (seealsoresponse toquestion 10).However,
heexpressed concerns about carbadox residues andthattherisksfromtheseresidues werelikely greater
thantherisksassociated withtheuseofgrowth promoters.
6.131 Dr.McLean replied thatcarbadox anditsmetabolite desoxycarbadox werenotpermitted in
meat, because thelatter compound wascarcinogenic. Inthecaseofcarbadox, awithholding period
wassettoachieve thesituation where there werenodetectable residues infood. Thethree naturally
occurring hormones were normally found inanimals andhumans. Thedatasupporting theuseof
trenbolone andzeranol wasextensive, withtoxicological end-points related totheirhormonal effects.
Finite residues werepermitted fortrenbolone andzeranol. Inthiswayanyriskofadverse effects was
managed through theMRL andsafety toconsumers wasassured.
6.132 Dr.McLeanfurthernotedthatolaquindoxwasconsideredtobegenotoxicandnotoxicitystudies
were available onitsmetabolites, therefore JECFA wasunable todetermine anADIorMRL.WT/DS48/R/CAN
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Benzylpenicillin waswidely usedasanantimicrobial agent inanimals andhumans. Allergenic potential
wasthemajor toxiceffect anditwasrecommended thatthetotalintake bekeptbelow 30micrograms
perdayforahuman. Benzylpenicillin showed nocarcinogenic potential. While carazolol showed
nogenotoxic orcarcinogenic potential, itwasapotent beta-adrenoceptor blocking agent. MRLs had
beenestablished forpigtissues. However, ifcarazolol wasusedinpigstoprevent stress during transport
toslaughter, therewasconcern thatresidues atthesiteofinjection could result inconsumers receiving
apharmacologically active doseofthedrug. Thetoxicity andresidue databaseforivermectin and
related compounds wasextensive andthedrugwasalsousedinhumans. Thecompound didnotshow
genotoxic orcarcinogenic potential andanADIandanMRL hadbeenestablished.
6.133 Theorganophosphoruscompounds(OP)weredescribedbyDr.McLeanaspowerfulneurotoxins,
andmostoftheuntoward effects wererelated tothedirect exposure ofoperators andothers. There
wasanewsyndrome oforganophosphate -induced delayed polyneuropathy -which wasofconcern
when there wasacute exposure.299TheOPhadbeenassociated withcarcinogenicity andthere were
reports ofacute poisoning associated withtheconsumption oftreated food. Very lowlevels ofthe
parent compound and/or metabolites might remain, although theycould notbedetected bysensitive
analytical techniques. Dr.McLean didnotcomment onmonensin oravoparcin because ofthelimited
amount ofregistration dataavailable which wasinpublic domain.
6.134 Dr.Ritter observed thatcarbadox wasreviewed bytheJECFA in1990. Initsreview, the
JECFA considered datafromshort-term andlong-term carcinogenicity, mutagenicity andreproduction
studies withcarbadox, anddatafrom mutagenicity andlongtermstudies ofitsmetabolites. JECFA
noted thatresults from several longtermfeeding studies inratsdemonstrated dose-related increases
inbothbenign andmalignant tumours atdoses above 1.0mg/kg BW/day. Positive findings werealso
noted in14ofthe15mutagenicity studies reported. JECFA concluded thatcarbadox appeared tobe
bothgenotoxic andcarcinogenic. Results from additional studies carried outwithquinoxaline- -
carboxylic acid,animportant metabolite ofcarbadox, indicated thattherewerenoeffects onincidence
oftumours, evenatdoses of100mg/kg BW/day. Inviewofthecarcinogenic andgenotoxic nature
ofcarbadox anddesoxycarbadox, ametabolite ofcarbadox, JECFA wasnotabletoestablish anADI.
Notwithstanding, theJECFA recommended MRLs of0.03mg/kg inliverand0.005 mg/kg inmuscle
ofpigs, based onandexpressed asquinoxaline- -carboxylic acid.
6.135 Theestablishment ofanADIandrecommendation ofanMRL reflected scientific confidence
intheexpressed residue levels being essentially devoid ofrisktohumans exposed todietary residues
onalifetime basis. Therefore, neither carbadox northegrowth promoting hormones should pose
potential adverse human health effects asaresult ofexposure todietary residues atorbelow theMRLs
specifiedbyJECFA.Notwithstanding,itwasnoteworthythatcarbadoxandatleastoneofitsmetabolites
wasbothcarcinogenicandmutagenic,whilethehormoneswerenotconsideredcarcinogenicormutagenic
atbiologically relevant doses. Inaddition, reliable residue monitoring andriskestimation ofcarbadox
residues wassomewhat complicated bythepresence ofbound residues, while residues ofthehormones
either fellwithin normal physiological range orcould bereliably andeasily measured.
Question 12:
Areresidues ofthesixhormones inquestion found inmilk ormilk products? Ifyes,howdo
thelevels ofthese residues compare tothose found inmeat from animals towhich hormones have
notbeenadministered? How dotheresidue levels inmilkcompare tothose found inmeat from
animals which have been administered these hormones forgrowth-promoting purposes? For
therapeutic orzootechnical purposes?
299M.Lotti, Toxicology 21,(1992) p.465.WT/DS48/R/CAN
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6.136 Dr.André replied thatresidues ofhormones ingeneral arefound inmilk. However, the
comparison withmeatlevels wasnotrelevant. Moreover, hormones were notsupposed tobeused
forgrowth promotion purposes inlactating cows, onlyinculled cows. Forspecific therapeutic or
zootechnical purposes, onlyindividual animals wereallowed tobetreated withhormones. Inthiscase,
themilkwasnottobedelivered forhuman consumption, aswasthecaseformany other drugs.
6.137 Dr.Arnoldnotedthatafterinjectionofapprovedproducts(nature-identicalmolecules)permitted
foruseintheEUtolactating cows, residues would befound inmilk. Depending ontheproduct it
could takeseveral milkings before theresidue levels would havereturned tophysiological values.
Residues found inmilkcould behigher, equal orlower, depending onwhich tissues werecompared
anddepending onmany other factors (dose, route, age,sex,withdrawal timeetc.)
6.138 Dr.Lucier indicated thatifresidues ofthehormones inquestion existed inthehuman body,
thenresidues would alsobepresent inhuman milk.
6.139 Dr.McLean replied thathormones arelipidsoluble andtherefore passintothefatportion
ofmilk. More polar metabolites would alsopassintomilk, butitmustbestressed thatthehormones
should notbeusedforgrowth promotion inlactating animals. When thevarious hormones wereused
fortherapeutic orzootechnical purposes, thedoses weremuch higher, therefore thelevels inthetissues
were higher. Ithadtobeexpected thatthelevels inmilkwould alsobehigher.
6.140 Dr.Ritter observed thatgrowth promoting hormones weregenerally onlypermitted foruse
inbeefcattle andvealcalves, andnotinlactating dairy cattle. Foxcroft andHess(1986) reported that,
atleastinthecaseofthenatural hormones, theresidue levels oftheadministered compound orit
metabolites inanimal products wereinsignificant incomparison tothelevels ofthesame steroids to
which human subjects might normally beexposed. Thiscould occur either (i)asaconsequence of
theendogenous production rateofsexsteroids inhuman subjects or(ii)asaconsequence ofthesteroids
inmeatand/or milkproducts derived from untreated animals.
Question 13:
What factors andprocedures should scientists consider inestablishing anappropriate assessment
ofthepotential adverse effects onhuman health from theuseofthehormones inquestion?
6.141 Dr.André responded thatanappropriate assessment ofthepotential adverse effects onhuman
health stemming from theuseofthehormones indispute "should bemore rigorous thancommon
veterinary drugs because oftheduration oftheiruseandtheverylimited, ifany,health benefits to
thetarget species".300Scientists should consider alldataavailable atthepresent timeindealing with
theadverseeffectsofeachcompound(seeresponsetoquestion8),theirmetabolitesandtheirmechanisms
ofaction, including theiraction atthelevelofexposure. Species-specific metabolite patterns should
becompared, using (asfaraspossible) acombination ofinvivoandinvitroexperiments. Studies
should include long-term feeding trials toaddress lifetimeexposure. Allstudies should beperformed
withcombinations ofthehormones indispute priortoregistration, toobtain valuable data. Theeffects
ofthetreatment onthekinetics ofother common drugs hadtobeassayed. Epidemiological studies
inhumans concerning cancer incidence andother hormone related diseases hadtobeinitiated.
6.142 Dr.Arnold indicated thefollowing should beconsidered: pharmacokinetic dataincluding
metabolism intestanimals andtarget animals, where available inhumans; data(preferably quantitative
data) from adequately designed toxicity studies insuitable animal species, including information on
genotoxicity/carcinogenicity, andnohormonal effect levels; target animal safety studies; efficacy
300Bridges, 1995 ECScientific Conference Proceedings, p.250.WT/DS48/R/CAN
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trials; epidemiological studies andother relevant observations inhumans; kinetic residue studies;
natural occurrence andhuman exposure fromallsources, including endogenous production ofthesame
orsimilarly acting substances; experience fromthehistory ofuseinhuman andveterinary medicine
(ifapplicable); andknown orproposed conditions ofuse. Amarketing authorization should only
begiven tostrictly formulated products (nottotheactive substances). Conditions ofuseshould be
fixed inabinding manner intheapproval process.
6.143 Dr.Lucier replied thatthere were several factors thatshould besystematically studied or
evaluated ifinformation wasnotavailable forassessment ofrisks from thehormones inquestion.
Ofspecial concern werepotential risksforcancer andnon-cancer effects (reproduction, development,
cardiovascular disease, etc.). Additionally, information oneffects insensitive sub-population should
beconsidered. Sensitivity could beconferred bygenetic predisposition (presence orabsence ofcancer
susceptibility genes), age(fetus, children ortheaged), gender, existing disease status, nutrition, and
co-exposure toother chemicals. These factors needed tobeconsidered, although itwasunlikely that
information onthem would everbecomplete foranygiven substance.
6.144 Dr.McLeannotedthatthetestingprotocolsusedincountriessuchastheUnitedStates,Canada,
theUnited Kingdom, Australia andbyJECFA wereadequate toassess theeffects oftheuseofhormones
onhuman health. Inaddition, there wasaneedforresidue monitoring programmes toensure that
residues inmeatwere lessthananyMRL which hadbeenestablished.
6.145 Dr.Ritter observed thatscientists considered awidearray oftoxicological endpoints andrisk
assessment procedures inestimating potential adverse effects onhuman health from residues ofall
chemicals, including anabolic hormones, other veterinary drugs andpesticides. Theissue offactors
andprocedures which were appropriate totheassessment ofthepotential adverse effects onhuman
health included toxicity studies which established thefollowing: which organs and/or systems were
most vulnerable tothetoxic effects andunder whatexposure conditions; thenature ofanydamage
and/or disease produced, andthedoseresponse relationship; thetimecourse fortheonset andany
progression oftheadverse effect; themechanism responsible fortheadverse effect; therelevance
oftheadverse effect observed inexperimental animals tohumans; thepotential impact ofbiological
mechanisms which ledtotheadverse effect butwhich, byvirtue ofthedoseutilized, werenotrelevant
totheassessment ofthebiological effect inhumans (thiswasparticularly important forthehormones
inquestion which were onlyassociated withadverse effects atdoses which were notconsidered to
beofrelevance totheassessment ofhuman health effects arising fromfoodresidues); whether itwas
appropriate toconsider theadverse effects observed asafunction ofathreshold mechanism, orrather
ifagenotoxic mechanism wasmore likely andhence athreshold mechanism would beaninappropriate
riskmodel.
6.146 Inaddition, Dr.Ritter noted thatitmight alsoberelevant toestablish ifthenature oftheresidue
wasdistinguishable fromnormal endogenous levels -thiswasparticularly relevant fortheuseofthe
natural gonadal hormones which resulted inresidue levels typically intherange ofuntreated animals;
whether appropriate andreliable methods existed fortheestimation andmonitoring ofresidues ofthe
hormonesfollowingtheiruseasgrowthpromotingsubstances;andknowledgeoftheuncertaintyinherent
inthehazard andriskassessment paradigm.
Question 14:
What arethepotential hazards, ifany,tohuman oranimal health oftheuseoflarge quantities,
ordoses higher thanthose recommended, ofanyofthesixhormones indispute? Andfrom the
administration ofthese hormones contrary togood animal husbandry practice and/or veterinary
practice? Canyouthink ofanyincentives ordisincentives forfarmers tousequantities larger
thanthose specified inthelabel ofthemanufacturers ortoadminister these hormones contraryWT/DS48/R/CAN
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togood animal husbandry practice and/or veterinary practice? Areyouaware ofanyevidence
ofsuchusebyfarmers?
6.147 Dr.André indicated thatahigher dosage, another route ofadministration than those
recommended fordelivery (other location forimplants, injectable solutions ofhormones, etc.), shorter
withdrawal periods, etc.,inshort, anydisrespect ofgood animal husbandry and/or good veterinary
practices,mightinducehigherlevelsofresiduesorchangesinmetabolitepatterns.Thefirstconsequence
would probably beamodification inanimal behaviour and/or health. Itwasreasonable tothink that
ahigher residue content inmeatwould enhance theriskofhazards tohuman health.
6.148 Theanabolic effect ofthehormones inquestion wasproportional tothedosage, withamaximum
effect.Farmerstriedtoobtainlargereffectsthroughadministrationofmoreimplantsthanrecommended,
although itwasnotevident thatadouble dose, evenatonetime, gaveabetter response. Insome cases,
aparenteral administration (e.g.intramuscular injection) produced amore rapid effect thanimplants,
andfarmers triedbythismean toobtain faster effects. Disincentives forfarmers touselarger quantities
would beadecrease ofthebenefit/cost ratio, butimplants were usually cheap. Incountries where
theywere inuseforgrowth promotion purposes, penalties duetohigher residue levels detected in
meatproducts compared totheMRLs might alsohavedissuasive effects onfarmers. When fiveout
ofthesixhormones indispute wereallowed inFrance, theexperience wasthatfarmers triedtogive
asecond doselater. They didnotrespect thewithdrawal period andtheyinjected another doseathalf
waythrough thetheoretical withdrawal period. Clearly theysawbenefit todothisbecause theeffect
waslonger atthetime. Dr.André further reported thatduring thefourtofiveyears when these
hormones wereallowed asgrowth promotants inFrance, themisuse ofother hormones continued and
theblack market wasalsopresent.
6.149 Dr.Arnold noted thattherewereconsiderable safety margins builtintotheestablished MRLs
forthesyntheticresidues.Aslongas"goodpractices"wereobserved,thecalculatedtheoreticalmaximum
daily intakes ofresidues would range around 5percentoftheADIforbothzeranol andtrenbolone
acetate. Ithadbeenshown thattheimplantation ofapproximately fivetimes therecommended dose
ofzeranol would havealmost noeffect onmaximum residue levels inthemuscle andliverofsteers
slaughtered onlyfivedaysafterimplantation. When atotaldosemore than100-times higher thanthe
recommended dosewasintravenously administered as6splitdoses overthree daystosteers andthe
animals wereslaughtered onthethirddayafterthelastdose, consumption ofthemeatofthese animals
would stillnothavecaused anabove-ADI intake ofresidues ofzeranol.301Thestudies available to
the32nd and34thJECFA showed thatresidues oftrenbolone werehighest ifheifers wereimplanted
shortly (15days) before slaughter. With respect tothecalculated theoretical maximum intakes, there
wasnodifference whether thisimplant wasthefirstorthesecond which theanimal hadreceived.
From these data, itseemed unlikely thateventhefrequent useofhigher doses, orrepeat doses or
slaughtering theanimals atearlier thanrecommended times afterimplantation, could result inresidue
intakes inexcess oftheADIbytheconsumer. Forthethree nature-identical hormones, thesafety
margins (theoretical residue intakes compared withendogenous production ratesofthemostsensitive
sub-population) were much higher thanforthesynthetic substances.
6.150 Dr.Arnold hadnoinformation withregard tomelengestrol acetate, norregarding incentives
ordisincentives forfarmers tousecombinations orillegal "cocktails" ofthese hormones. Although
these pellets andanother devices hadbeendeveloped togiveoptimum results when thedosewas
respected,thisdidnotnecessarilypreventsomefarmersusingmoreimplants.Butthisdidnotnecessarily
cause higher residue levels inthecarcass. Ontheother side,itwasclearthatiftwice theamount was
injected directly, alllevels increased inplasma andintissues, notnecessarily inalinear way, but
significantly. Thatwasthedifference between aslowrelease device (likeearimplant) andadirect
301Food andNutrition Paper 41,pp.44-45, FAO (1988).WT/DS48/R/CAN
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injection. Ontheother hand, thelongtermrelease ofhighdoses might influence thepattern ofhormone
excretion intheanimal 'sbody andthiswastheintention ofusing suchcompounds.
6.151 Dr.Lucier indicated thatanyincrease inthemagnitude ofexposure would likely increase any
potential risks, buthedidnotconsider himself qualified toanswer therestofthisquestion.
6.152 Dr.McLean responded thatthehormones inquestion, withtheexception ofMGA, werenot
wellabsorbed when administered orally. Grossly excessive doses might haveaneffect onconsumers
ofmeat, butthese effects were likely tobemildandtransient andcould passwithout being noticed.
Thedoseprescribed under "good practice" wassufficient toexertacommercially satisfactory response,
andtherewasnoadvantage inexceeding thisdose. Thedosesuggested bythesponsor gavetheoptimum
response andtherefore, within limits, there wasnoneedorbenefit inadministering more thanwas
suggested. Theregulatory authorities alsoexamined theeffects ofoverdosing during theregistration
process. Most regulatory authorities, including JECFA, required thatdataforresidues setting did
takeintoaccount doseratesthatwere inexcess ofwhatwasnormally used(generally atleasttwice
andsometimes more) sothattheeffect ofoverdosing orvariations inuptake could beseen. Incountries
where theuseofthese compounds waspermitted, thereweregoodeducational campaigns forfarmers
astothecorrect useandthereasons whytheprescribed doseshould notbeexceeded, andthepenalties
thatexisted ifonedid. Theresults from residues surveys showed that,byandlarge, there wasno
exceeding oftheMRL. InAustralia, trenbolone andzeranol hadbeentargeted inresidue surveys
veryspecifically looking forviolations, andtoallintents andpurposes violations didnotoccur. Even
iftherewasmisuse, andthatwasdifficult toprove, therewerestillnoresidues thatexceeded theMRL.
Asimilar situation existed withthenaturally occurring hormones, where itwasnotpossible todetermine
whether ornotaviolation hadoccurred because thelevels thatwerefound inthecarcass fallwithin
thenormal range.
6.153 Dr.McLean observed, however, thatincountries where theusewasnotcontrolled andthere
wasnofarmer education campaign andwhere itwasdifficult toapply apenalty, thentheMRL was
significantly exceeded. Oneoftheimportant factors oflegalizing these compounds wastoconduct
aneducation campaign andtoputinplacemonitoring procedures toensure thattheMRL isnotexceeded.
What wasimportant withthemaximum residue limitistounderstand thatitwasalegallimitandnot
ahealth limit. Inother words, exceeding oftheMRL didnotrepresent ahazard tohealth butrather
alimitatwhich theauthorities tookaction. However, toexceed theMRL would notbeconsidered
tobegood practice.
6.154 Dr.Ritter noted thatitwasverydifficult, ifnotimpossible, toestimate potential hazards which
might beassociated withtheadministration ofthehormones contrary togoodpractice, asthemagnitude
ofthepotential hazard would berelated tothenature, extent, frequency andmagnitude ofthe
inappropriate administration. Ithadbeenreported thatinthecaseoftheanabolic hormones andusing
commerciallyavailableimplants,repetitiveimplantationhadonlylittleinfluenceontheresidueprofile.302
Similarly, fullandhalf-dosages ledtosimilar hormone levels inedible tissues which, inthecaseof
theendogenous hormones, werewithin thephysiological range. Further, unlawful andimproper use
ofoestradiol might result inresidue levels some 300-fold inexcess ofestablished tolerance limits, and
yetitwasvirtually impossible tovisualize anyhazard tohumans ingesting meatfromanimals treated
with zeranol.303Similarly, when steer calves were implanted with zeranol inaccordance with
recommended procedures, themargin ofsafety forconsumption ofedible products wasgreater than
25,000 and150,000 forliverandmuscle, respectively. While thiswork didnotspecifically address
theissue ofpotential abuse, thelarge margins ofsafety postulated bytheauthors suggested thateven
under limited circumstances ofabuse, itwasunlikely thatconsumers would beexposed tounacceptable
302Hoffman andEvers (1986).
303Truhaut etal.(1985).WT/DS48/R/CAN
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risks.304Incountries where useofthese hormones, thesixhormones inparticular, hadbeenpermitted
foraveryextended period oftime, most notably Canada andtheUnited States, monitoring and
complianceprogrammeswhichhadbeenconductedformanyyearsconsistentlydemonstratedthatresidue
levels wereentirely within recommended limits andthatinstances ofviolative residues, thatwasresidues
which would indicate abuses taking place, hadalmost never beenreported. Itseemed thatatleastin
those jurisdictions where usewaslawful, thepracticality ofabuse hadnever become areality. There
werefewandisolated examples ofviolative residues inthose countries where usehadbeenpermitted.
Question 15:
What aretheconsequences interms ofpotential hazards tohuman oranimal health from the
useoflegally marketed combinations, iftheyexist, orillegal "cocktails" ofthesixhormones in
dispute foranimal growth promotion? Have legally marketed combinations beensubject tothe
same testing regime aseachoftheir individual components? Isthere anyevidence ofsynergistic
effects ofcombinations ofhormones? Canyouthink ofanyincentives ordisincentives forfarmers
tousecombinations orillegal "cocktails" ofthese hormones?
6.155 Dr.André replied thatspecific consequences stemming from theuseoflegally marketed
combinations were notknown. Iftheyexisted potential hazards could beduetosynergistic and/or
additive effects oftheresidues. Thisanswer wasalsovalidforillegal "cocktails" ofthesixhormones
inwhich more thantwocomponents could bepresent. However therewasanother important potential
hazard fromthesystematic useofthesecombinations: theirusecould result inmodifications ofkinetic
parameters ofother drugs. Forexample, trenbolone andtestosterone were shown todramatically
decrease theelimination rateofsulfamethazine, trimethoprim andantipyrine ingoats, withopposite
experimental results inrats. Asaconsequence, residue levels could behigher thantheMRLs at
slaughter, evenwhen legalwithdrawal periods wererespected.305Recently, theincrease ofthelevel
ofbetaagonist residues inliverowing toconcomitant oestradiol treatment hadbeendemonstrated in
calves.306
6.156 Dr.André wasaware ofonlyonecombination (TBA +oestradiol) having beenassayed by
theJECFA inthecontext ofresidue determination insteers. Noother combinations hadbeentested
whereas individual components hadbeentested fortoxicological effects. Evidence ofsynergistic effects
ofcombinations ofhormones existed andwere wellstudied mechanisms. Forexample, concerning
endocrinological therapy inhumans, combinations ofoestrogen andprogestin hormones wereused;
oestrogensinducedthesynthesisofspecificreceptorsforprogestins,whichcouldthenexerttheirspecific
action. Legally marketed combinations hadbeendeveloped onthebasisofsynergistic effects oftheir
components ongrowth promotion.
6.157 Incentives forfarmers tousecombinations (legally marketed) orillegal "cocktails" ofthese
hormones werefrequently reported byofficial control bodies, since farmers tended tothink thatthe
more hormones used, thebetter theanabolic effect. Moreover, interactions between these hormones
andother endogenous biochemical parameters (e.g.corticoids, IGF, etc.)were ofgreat importance
forhuman health andcould bedocumented.
6.158 Dr.Arnold noted thatfixed combinations wereregistered intheform ofstrictly formulated
veterinary medicinal products andweredifferent fromillegal mixtures forwhich theterm"cocktail"
hadbeencoined inEurope. Fixed combinations werenotonlyusedforgrowth promotion butalso
304Sundlof andStickland (1986).
305VanMiert (1988).
306Kuiper, 1995 ECScientific Conference Proceedings, p.377.WT/DS48/R/CAN
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forthepurposes permitted intheEuropean Union. These combinations wereapproved andregistered
bythecompetent authorities under therespective rulesgoverning veterinary medicinal products. The
applicant hadtojustify thecombination andhadtodemonstrate thequality, efficacy, target animal
safetyandconsumersafetyoftheseproductsbeforetheycouldbemarketed.Forthesetypesofregistered
products, there wasnoevidence ofahazard tohuman health.
6.159 Dr.Arnold reported thatthepharmacodynamic andtoxic effects ofpractically allpossible
combinations ofoestrogens, progestins andandrogens hadbeenstudied inwhole animals, organs, tissue
andcellcultures, andother invitrosystems under agreat variety ofconditions. There wasample
evidence ofbothsynergistic andantagonistic effects. Such effects physiologically played important
rolesinendocrinologyandmetabolism.Thecurrentunderstandingofthesephenomenaclearlyindicated
thatconcerns overhuman health hazards arising from combinations ofminute amounts ofresidues
inmeatwere notjustified.
6.160 Theflourishinggreymarketinotherveterinarymedicineswithin,forexample,Germanyshowed
thatfarmers triedbypassing official distribution channels when purchasing otherwise licensed high
quality products, mainly inorder tosavecosts andprevent having topaytheveterinarian. Towhat
extent "good practices" intheusewereotherwise followed remained subject tospeculation. Itseemed,
however, thatnotallruleswereviolated atonetime. Thesituation withprohibited substances (e.g.
hormones, chloramphenicol) andwithabused substances (e.g., clenbuterol) wascompletely different.
There wasclearly ablack-market where the"dirty products" prevailed. Theavailability ofreasonably
priced legal alternative products could beanincentive formany farmers tolegalise theirpractices.
Whether thiswould eliminate illegal cocktails nowthattheblack-market hasbeenwellestablished,
remained entirely speculative.
6.161 Dr.Lucier indicated thatthere wasadefinite research need inareaofsynergistic and/or
antagonistic responses tocombinations ofendogenous orexogenous hormones. Based oncurrent
knowledge, itwaslikely thatinteractions existed butitwasimpossible tosaywithanydegree of
confidenceforagivencombinationwhethertheinteractionwouldbesynergistic,additiveorantagonistic.
There waslimited evidence tosuggest thatsynergistic responses wereoccurring although therelevance
ofthese findings tohuman riskshadnotbeenshown. Dr.Lucier noted thatthesame combinations
ofhormones, atcertain levels, could havebothsome adverse health effects andsome positive ones.
6.162 Dr.McLean replied thatthelegally marketed combinations hadbeenexamined byregulatory
authorities toensure thatresidues didnotexceed levels seeninnormal animals ortheprescribed MRL.
There weresynergistic growth promoting effects seenintreated animals. Illegal "cocktails" weremostly
found incountries where theuseofhormones wasprohibited, resulting intheestablishment ofanillegal
market. They werenotnormally usedwhere thefullrange ofdrugs wasavailable because there was
noadvantage intheuseofillegal drugs, andregistered products wereusually cheaper andofconsistent
quality.
6.163 Dr.Ritter noted thatwhen growth promoting hormones wereusedascombinations, thisuse
didnotalterexistingMRLswhichhadbeeneitherrecommendedinternationallyorestablishedbynational
regulatory authorities, andhence theuseofhormone combinations wasnotlikely tohaveanydirect
adverse consequences interms ofhuman health. Inthecaseof"illegal" cocktails, itwasimpossible
tospeculate onthepotential foradverse effects ineither humans oranimals, asthispotential would
beafunction ofthenature ofthecocktail, thespecies ofuse,thedose, frequency andduration ofuse,
andarange ofother factors which could notbeassumed.
6.164 Ingeneral, safety (toxicology) evaluations ofdrugs, pesticides andother foodcontaminants
werecarried outonsingle compounds only, rather thanascombinations. There wereseveral reasons
forthisapproach which included prior pharmacological andbiochemical knowledge thattoxicity
associated withcombinations wasnotlikely toproduce effects greater thanthesumoftheindividualWT/DS48/R/CAN
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components. Onamore practical level, itwasdifficult tocontemplate thebroad range ofpossible
combinations which would bethesubject oftesting. Finally, asdifferent commercial interests might
beinvolved intheproduction andsaleofvarious growth promoting hormones, proprietary interests
would make itunlikely thatcombinations could beevaluated toxicologically. Insome cases, theefficacy
ofhormone combinations hadbeenevaluated. Inthecaseofcombinations oftrenbolone withzeranol
oroestradiol, forexample, itwasfound that(i)thecombinations wereequivalent inyoung bullsand
steers, (ii)anabolics containing oestradiol weremore effective invealcalves, and(iii)thecomposition
andquality ofthemeatwasnotmodified bytheuseofcombinations when compared tosingle use.307
Aswithanydrugorunlawful drugcombination, farmers sometimes wereunder theincorrect impression
thatcombinations which hadnotbeenevaluated might provide significantly enhanced efficacy over
those which hadbeenapproved foruse.Suchimproper useofillegal cocktails could affect withdrawal
times andresidue limits andmight, insome jurisdictions, result incompliance andenforcement as
disincentives totheunlawful useofnon-approved cocktails. Dr.Ritter noted thatitmust alsobe
recognized thatthequest foreverimproved yieldcould leadsome producers totheuseofunapproved
drugcombinations.
6.165 Dr.Randell indicated thatthemonographs which wereprepared byJECFA atthe32ndsession
clearly indicated thattrialsweredoneonmixed implants aswellasonsingle substance implants. JECFA
hadconsidered such mixtures asoestradiol together with testosterone, oestradiol together with
progesterone,oestradiolbenzoatetogetherwithtestosteronepropionateandalsooestradiolwithtrenbolone
acetate under theoestradiol evaluations. These wereknown toJECFA atthetime, andthepharma-
kcenetics ofthese substances astheywere gradually metabolized andexcreted bytheanimals were
studied bytheexperts atthattime. Moreover, theinformation which wasavailable toJECFA included
carcinogenicity studies forallofthesubstances concerned.
Question 16:
Which substances inaddition tothehormone compounds atissue arepresent inthecommercially
available products marketed foranimal growth promotion? Arethere anypotential adverse effects
onhuman oranimal health? Question 33: Further toquestion 16,arethere other substances
inhuman implants potentially dangerous tohuman health?
6.166 Dr.André noted thatifthequestion referred totheexcipient ortopotential sub-products of
synthesis, thesedata,asproperty ofmanufacturers, remained confidential. Concerning thesimultaneous
useofother drugs marketed forgrowth promotion (e.g. antibiotics), theirresidue levels could be
modified bytheuseofthehormones (seeresponse toquestion 15),sothatapotential adverse effect
onhuman health could appear.
6.167 Dr.Arnold indicated thatother growth promoters (antibacterials) were usedunder thefeed
additives legislation oftheEuropean Communities (e.g., flavomycin, virginiamycin, zincbacitracin,
salinomycin, monensin, lasalocid). Thereview process wascentralised. There werenoknown potential
adverse effects onhuman oranimal health iftheseadditives areproperly used. Theuseofglycopeptide
avoparcin wasrecently withdrawn asaprecautionary measure because ofsome suspicion that
glycopeptid-resistance selected bytheuseinanimal production could betransferred tohuman-pathogenic
enterococci.
6.168 Dr.Lucier responded thattherearemany known casesofthepresence ofoestrogenic substances
arising fromplantproducts, pesticides andindustrial contaminants. Itwaslikely thattheoestrogenic
potency ofthese substances, taken together, exceeded thatfrom meat residues ofthesixhormones
inquestion.
307Bouffault andWillemart (1983).WT/DS48/R/CAN
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6.169 Dr.McLean stated thatthere wereanumber ofnon-active components usedintheimplants
toensure thatthedrugwasdelivered overthelifeoftheimplant. These included acarrier forthe
drugandaninertmatrix which made uptheimplant. Theformulation wasapproved bytheregulatory
authorities ineachcountry. Thecomponents were often used inhuman andother animal drug
formulations andtheirsafety hadbeenestablished.
6.170 Dr.Ritterrepliedthatthecompositionofcommerciallyavailableproductswasgenerallyregarded
asproprietary information. Consequently, hehadnodirect knowledge oftheidentity ofthesubstances
other thanthehormones which might bepresent incommercially available hormone preparations.
Question 17:
What aretheimplications forhuman oranimal health ofresidues from misplaced implants or
improper administration, i.e.when administered differently than indicated inthelabel ofthe
manufacturer, ofanyofthesixhormones indispute ?
6.171 Dr.André indicated thattheconsumption ofmeat(orofanymeat-containing foodpreparation)
containing amisplaced implant could beahazard forhuman health, inparticular forchildren, fetuses,
pregnant women orimmunodeficient people. Misadministration ofanyofthesixhormones indispute
could change thekinetics ofelimination ofthese hormones andinduce asubsequent higher level of
residues. Thiscould become arealhealth hazard ifthere wassystematical misuse.
6.172 Dr.Arnoldobservedthattheremightbeaconcernonlywheremisplacement(growthpromotion)
orimproper administration (therapy, zootechnical treatment) leadtoconsumption ofawhole implant
orinjection site. Otherwise, residues remaining inthecarcass oftherespective animal would have
noeffects, eveniftheywere higher thanwould beexpected if"good practices" hadbeenapplied.
Theworst caseassumption wasthatawhole fresh implant containing oestradiol oranesterofthis
hormone isconsumed, because theimplanted dosewashigher thanthedoses injected fortheother
purposes andorally active oestradiol-doses werelower thantherequired doses oftheother hormones.
Ifthisentire dosewasingested atonce, onlytransient effects onhormonal feedback mechanisms would
beexpected. Clear hormonal effects would occur ifanentire injection sitewasprocessed, e.g.,into
ameatcontaining product andthesame person would eatthewhole product individed portions over
acouple ofdays.
6.173 Dr.Lucierstatedthatimproperormisplacedimplantscouldverywellincreaseresidues,thereby
increasing thepotential riskofthehormones inquestion. Preventive strategies formisuse needed to
involve veterinary supervision, educational programmes, monitoring andstiffpenalties forabuse.
6.174 Dr.McLean replied thattheimplants would likely bedetected iftheywereeaten because the
matrix could notbechewed. Ifswallowed, theywould notbedigested butwould passthrough the
human gastrointestinal tractlargely unchanged. Theimplications ofmisplaced implants maynotbe
ofgreat concern because theywere often placed under theskinandremoved atslaughter orduring
processing. Inorder tofacilitate correct andeasyadministration, applicators weregenerally available
fromthepharmaceutical companies. Oneofthefeatures ofinjections subcutaneously intheearwas
thatthere wasnomassive reaction atthesite.Itwasspecifically designed, andalltheresidue studies
werecarried out,withtheimplant injected intheear.Theaimofinjecting ittherewastogetprolonged
andslowrelease atlowlevels overaperiod oftime. Itwasspecifically designed tobethatway.
Moreover, theinjections wereusually implanted intheearbecause itwasveryeasytopalpate apellet
oranimplant under theskinoftheearwhich wasasecond wayofidentifying treated animals.
6.175 Dr.Ritter responded thatthegrowth promoting hormones weregenerally administered asfeed
additives orasimplants. Intheevent thatimplants were implanted atsites other thanthose
recommended, itwaspossible thatthese sitescontain unacceptably highresidue levels ifutilized asWT/DS48/R/CAN
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asource ofhuman food. Theselection oftheearasasiteofimplantation rather thanother siteswas
because itwasatissue which normally didnotenter thefoodchain anditmade identification ofthe
source ofthematerial veryeasy. Injection siteresidues, which could bemuch higher thannormal
tissue residue levels, were thusextremely unlikely toenter thefoodsupply. Theextent towhich
acceptable residue levels might beexceeded would depend ontheexact siteofimplantation andthe
withdrawal period involved. Theimplication forhuman health would inturnberelated tothese two
variables.
6.176 Dr.Ritter indicated thatillegal injection ofoestradiol preparation could produce injection site
residues which largely exceeded tolerances. Inthecaseoffeedadditives, improper usemight imply
useofapproved drugs innon-approved species, improper dose, improper combinations, improper
duration ofuseandimproper withdrawal periods. However, theprovision ofhuman safety wasassured
through theestablishment ofmaximum residue levels, levels considered tobesafeifconsumed by
humans inthedietforanentire lifespan. Intheevent thatanyoftheimproper useconditions noted
above occurred, andtotheextent thatsuchimproper usewould impact onfinalresidue levels, human
safety wasassured through appropriate monitoring ofthefoodsupply forcompliance withapproved
MRLs.
Question 18:
What aretheeffects ongrowth promotion oftheuseoffemale hormones onmale animals and
vice-versa? Arethere anypotential adverse effects onhuman oranimal health from suchuse?
6.177 Dr.André saidthattheeffects ofhormones ongrowth promotion wassex-dependent. The
useofmalehormones associated withfemale hormones (ratio 10:1) inheifers hadthebestanabolic
effect without sexual behaviour problems andvice-versa. Concerning thehuman health, thelevelof
residues hadtobetaken intoaccount, whatever thegender ofthemeatproducing animals. Concerning
animal health, theuseofoestrogenic compounds inmaleanimals wasshown toresult insquamous
metaplasia, hyperplasia ofthecollecting ducts andfibromuscular hypertrophy intheprostate andbulbo-
urethral gland, fibromuscular hypertrophy andhypoplasia oftheepithelium intheseminal vesicles
andepididymis andimpaired testicular development. Infemale animals, oestrogen treatment resulted
insquamousmetaplasiaandfibromuscularhypertrophyintheBartholin'sgland,hyperplasiaandsecretory
activity inthevagina andcervix, andimpaired follicular developments intheovaries. Thelatter could
alsobeobserved when females weretreated withandrogens, impaired follicular developments inthe
ovaries sometimes resulted incystic ovaries.
6.178 Dr.Arnold indicated thatsupplemental oestrogens incastrated males increased growth rate,
presumably through anincrease ofendogenous levels ofgrowth hormone, improved feedefficiency
andreduced aggressive behaviour. Testosterone wasmainly usedtoslowdown therelease rateof
oestradiol because blood levels required foranabolic effects could notbereached withimplants. No
adverse effects wereknown onhumans. Theuseinanimals ofhormonally active growth promoters
might havebehavioural side-effects inindividual animals.
6.179 Dr.Lucier observed thatsome effects, possibly adverse, could occur intheanimals receiving
thegrowth-promoted substances. These effects could include feminization ofmale animals and
masculinization offemale animals based onbothmolecular andbiological endpoints. These effects
should notoccur inpeople eating meatcontaining residues attheMRL ofthehormones inquestion.
6.180 Dr.McLean commented thatthere wasawiderange ofcombinations anddoses available for
arange oftypes ofcattle. Thecombinations weredesigned toensure maximum doseresponse inthe
target animals. These combinations hadbeensubjected tostudies toensure thattheresidue levels did
notexceed prescribed values.WT/DS48/R/CAN
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6.181 Dr.Ritter indicated hehadnoexpertise inthisarea.
Question 19:
What differences existbetween thetherapeutic orzootechnical useofhormones permitted bythe
ECandtheuseofhormones forgrowth promotion purposes, aspermitted intheUSandin
accordance withgood animal husbandry practice and/or good veterinary practice, interms of
administered quantities, residue levels andpotential adverse effects onhuman oranimal health?
Docommon therapeutic orzootechnical usesofthehormones inquestion intheECinvolve large
scale (ie.,whole herd) orrepetitive treatments?
6.182 Dr.André observed thattheuseofthehormones fortherapeutic orzootechnical purposes
andforgrowth promotion purposes wasnotcomparable formany reasons. Thenumber ofanimals
treated wasdifferent, asfortherapeutic useveryfewanimals weretreated. Forzootechnical purposes,
thenumber washigher butremained limited. There were nosystematic, repetitive treatments. For
growth promotion purposes, thenumber ofanimals seemed tobelarge.
6.183 Inaddition, Dr.André stressed thatthefuture oftheanimals treated either fortherapeutic or
zootechnical purposes orforgrowth promotion purposes wasverydifferent. Inthefirstcasetheanimals
usually remained onthefarmformonths oryears aftertreatment andtheproblem ofresidues was
notofconcern. Theonlycomparable situation wasforoestradiol benzoate, forwhich, incaseof
unsuccessful treatment inacow,awithdrawal period oftwomonths hadtobeobserved. Inthesecond
case, theanimals were slaughtered weeks ormonths afterthetreatment. Furthermore, thedelivery
conditionsdiffered.IntheEC,thetherapeuticuseofthesehormoneswasparticularlyregulated.Finally,
Dr.André noted thatnoneofthese therapeutic/zootechnical useswould change thelevelofresidues
ofhormones inmeat onlarge scale asoccurred from growth promotion use. Noscientist hadsaid
thatitwasabadthing tousethesehormones fortherapeutical use;theiruseonalargescaleforgrowth
promotion wasnotthesame thing.
6.184 Dr.Arnold replied thatthetotaldosecontained inanimplant ofoestradiol-17 wasmuch
higher thanthedoseinjected fortherapeutic purposes because theimplant contained thequantity needed
overalongtime(e.g., 200days). Onadaily basis, however, thedoseinjected wasmuch higher,
andtherefore, tissue residues (excluding theinjection site)aftertreatment weremuch higher ifcompared
withtheresidues measured atanytimeafterimplantation. Norepresentative datawereavailable for
progesterone ortestosterone thatwould permit comparisons. With theexception ofoestrus
synchronisation, individual identified animals were treated.
6.185 Dr.Lucier indicated thatitwaspossible thatextraordinarily lowresidues (likely non-detectable)
ofthehormones could bepresent atslaughter iftheanimals hadreceived thehormones fortherapeutic
use(seeresponse toquestion 3).
6.186 Dr.McLean replied thatthetherapeutic useofhormones generally required theadministration
ofalarger dose, which inturnresulted ingreater levels ofresidues. Thepersistence ofthese residues
depended onthedose, formulation andsiteofadministration. Individual animals orgroups ofanimals
wereoftentreated atonetime, butrarely thewhole herd. Treatments mayberepeated. Treated animals
should beidentified sothattheywerenotslaughtered forhuman fooduntilasuitable withdrawal period
hadelapsed. Itwasoftennecessary towithhold milk. When hormones wereusedforgrowth promotion,
theimplants slowly released theactive ingredients andthere wasnever ahighpeakofhormones in
thetissues. Inthecaseoftherapeutic use,there often wasasignificant peak.
6.187 Dr.Ritter responded thattheprimary difference between thetherapeutic and/or zootechnical
usesofthehormones permitted bytheCommunity when compared togrowth promoting usesrelated
primarily tothefrequency ofuse,dose, andthepotential number ofanimals tobetreated. Inallcases,WT/DS48/R/CAN
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therapeutic and/or zootechnical useswould generally involve lower doses atlessfrequent intervals
infewer animals, and,inthecaseoftheCommunity, wasrestricted toadministration byalicensed
veterinarian. Notwithstanding, atleastinthecaseofthenatural hormones, theapproach adopted by
theCommunity fortherapeutic/zootechnical usesprovided forresidue levels which fellwithin therange
oflevels normally found inuntreated animals. While thebasis foruseofthese hormones forgrowth
promotion purposes wasfundamentally different, theresulting residues appeared, nevertheless, toalso
fallwellwithin thenormal physiological range.
Question 20:
Doyouconsider thattheconditions imposed bytheECforthetherapeutic orzootechnical use
ofthese hormones canachieve itsaimofavoiding anypotential adverse effects onhuman health
resulting from residues inmeat from animals treated forsuchpurposes?
6.188 Dr.André commented thatthisquestion wasnotrelated toascientific expertise, andasa
consequence,hecouldonlygiveapersonalopinion.Whenusedfortherapeuticorzootechnicalpurposes,
these hormones wereusedby(orunder thecontrol of)veterinarians. Thisguaranteed thattheywere
usedaccording totheindications forwhich theyhadbeenregistered (i.e.dosage, routeofadministration,
withdrawal period). Moreover thesehormones wereusedeither onindividual animals orinwelldefined
herds, usually inorder tosynchronize oestrus. Inthiscase, theanimals werereproducting animals,
theyhadahighvalue andwould beslaughtered onlyseveral years afterthetreatment. Theproblem
ofresidues wasnotofconcern forthese animals. Itcould notbecompared withtheuseofthese
hormones forgrowth promotion. When usedfortherapeutic purposes, these drugs were needed to
restore health andthebenefit/cost ratiowasveryhigh. When usedforzootechnical purposes, the
consequence foragreat majority oftheanimals wastobecome pregnant and,exceptionally, tobe
slaughtered.
6.189 Dr.Arnold indicated thattheproducts which could beusedwerereviewed according tothe
criteria established fortheapproval process ofveterinary medicinal products, including established
withdrawal times. Iftheapproved conditions ofusewere observed, anypotential adverse effects on
human health resulting from residues inanimals treated forsuchpurposes could beavoided.
6.190 Dr.LucierrepliedthattheECmeasuresforthetherapeuticorzootechnicaluseofthesehormones
could notguarantee "zero risk", although thepotential riskswere likely lower thanrisksfrom their
useasgrowth promoter.
6.191 Dr.McLean responded thathewasnotfully familiar withpractices intheCommunity.
However, studies onantibiotic residues haveshown thattheinvolvement ofveterinarians inthecontrol
andprescribing ofantibiotics onfarms didnotalways guarantee thatresidues would becontrolled.
Thesame situation would probably existwithhormones.
6.192 Dr.Ritter recalled thattheCommunity allowed theadministration ofoestradiol, testosterone
andprogesterone toanimals fortherapeutic andzootechnical purposes onlyunder conditions which
restricted administration toaveterinarian, required registration oftreatments andasufficient withdrawal
period. Given thenature ofconditions imposed forsuchuse,itwasunlikely thatresidues resulting
fromexogenous application ofthegonadol hormones would bepresent asresidues. Notwithstanding,
growth promotion usesofthenatural hormones similarly would notresult inresidue levels inexcess
ofthose expected inuntreated animals.WT/DS48/R/CAN
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Question 21:
Isthere adifference interms ofpotential adverse effects onhuman oranimal health between
residues ofthese hormones administered asfeedadditives, compared toresidues ofthese hormones
which areimplanted orinjected?
6.193 Dr.André indicated thatasfarasheknew, themetabolism ofthese hormones administered
asfeedadditives hadnotbeenstudied. Toproduce residues meant thattheywereabsorbed, andthat
theyareefficient andmetabolised. Nevertheless, theiruseasfeedadditives could induce ariskfor
people potentially incontact withthese hormones (factories, farmers, children etc.), andariskfor
theenvironment.
6.194 Dr.Arnold responded thatmelengestrol acetate wasonlyusedasafeedadditive. Zeranol
andtrenbolone acetate wereusedasimplants only. Oestradiol-17 ,progesterone andtestosterone were
administered bydifferent routes including injection andimplantation. Itwasdifficult tomake
comparisonsaboutpotentialeffectsduetomeansofadministrationbecausethereweretoomanyvariables
intheequation (chemical nature, dose, route, formulation, target species). Ifalluseswerecarried out
incompliance withtheestablished conditions ofuse,theremaining residues could beregarded assafe.
Thesafety margins might varyfromonecondition totheother andtheconsequences ofnon-compliance
might alsobedifferent.
6.195 Dr.Lucier commented thattheresidues would bethesame interms ofchemical structure,
although theresidue levels could bedifferent quantitatively.
6.196 Dr.McLean observed thatthecontrol oftheadministration ofhormones toanimals asfeed
additives wasbyremoving themfromfeedatagiven time. Inpractice, because ofcarry-over infeed
mixing plants andresidues instorage silosandfeeding stalls, there wasnotasharply defined cut-off
point. Inthecaseofantibiotics, itwasoften necessary touseadedicated mixing planttoavoid carry-
overfromtreated tountreated feed. Thedoseabsorbed could alsovarydepending onfoodintake and
absorption from thegut.There wasalsotheproblem ofaccurately mixing small amounts ofpotent
active ingredients through thefeed. Injection wasmoreaccurate andreliable, andonbalance themethod
ofchoice.
6.197 Dr.Ritter replied thatpotential adverse effects onhuman health invariably related toresidues
which exceeded acceptable limits. Proper useofgrowth promoting hormones aseither implants or
feedadditives might result inresidues which, ifusedinaccordance withrecommended andapproved
practice, should notexceed acceptable levels regardless ofthemethod ormeans ofadministration.
Henoted thatimproperly placed implants could result infailure toproperly identify implantation sites
atslaughter andcould thereby result inexcessively highresidues inthose tissues which would otherwise
beidentified andremoved. Properly located implants, when implanted inaccordance withapproved
practice, should notresult inunacceptable residues andhence thereshould belittleimpact onpotential
adverse human health effects regardless ofthemethod orroute ofadministration.
Question 22:
With respect toZeranol, Trenbolone andMGA, what arecurrently thetechnological limits of
detection and/or quantitation ofresidues? Ie.,what isthelowest levelofresidue which canbe
detected?
6.198 Dr.Andréobservedthatthesehormoneswereconsideredasclassicalbannedcompounds(within
theEC). They werecontrolled withmethods whose limits ofdetection (LD)wereequal orbetter than
2ppb. However, mostmethods inuseforscreening purposes ofthese hormones wereimmunological
ones. Their reallimits ofdetection were usually lower than0.5ppb. Mass spectrometric methodsWT/DS48/R/CAN
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allowed confirmation ofresults atthislevel. Furthermore, using techniques withhighperformance
output suchashighresolution massspectrometry orMS-MS, thelevelof10ppt.orsocould bereached.
6.199 Dr.Arnold replied thatthetechnological limitations would allow thequantification ofcertain
residues incertain tissues atconcentrations below 1ng/kg. Thiscould not,however, beachieved in
routine monitoring. Moreover, thelimits ofdetection ofcurrent routinely applied methods mayvary
from country tocountry (within certain limits). Only fewmethods hadbeen internationally
collaboratively studied according tointernationally harmonised protocols. Only fewmethods were
fullyvalidated inaccordance withthecriteria firstdefined bytheCodex Alimentarius andlateradopted
bytheEEC inDirective 85/592.
6.200 Dr.McLean explained thatthere were twobasic types ofassays used. Screening methods
wereusedtodetect drugs formetabolites atthelevelofinterest. These hadhighsample throughput
andaimed toavoid falsenegative results. Confirmatory methods provided unequivocal identification
ofthedrugand/or metabolites atthelevelofinterest. Thecostofanalysis wasconsiderably greater
thanforscreening methods. These methods were constantly being reappraised.
6.201 Dr.Ritter responded thatmethodology forMGA hadbeenreported308withalimitofdetection
of5ppb.andalimit ofquantitation of10ppb., bothinfat,thetarget tissue forthisresidue. LC
methodology forthetrenbolone acetate hadbeenreported309withalimitofdetection of2ppbinmuscle
andliverfor-trenbolone, andalimitofquantitation of2ppbinmuscle and4ppbinliverfor-
trenbolone inliverandkidney. GC/MS methodology forzeranol hadbeenreported byCovey etal
(1988) withalimitofdetection of0.1ppb.andalimitofquantitation of0.2ppb.inliverormuscle.
The Joint FAO/WHO Expert Committee onFood Additives (WHO, 1988) reported that
radioimmunoassays could detect freeandconjugated -and-trenbolone atlevels of75ng/kg intissues.
Radioimmunoassays weregenerally regarded asappropriate screening methods only,while conventional
analyticalproceduressuchasgaschromatography/liquidchromatography/massspectrometryaregenerally
regarded assuitable forconfirmatory analysis.
Question 23:
Canyoudescribe howtheECbanisenforced intheEC'sinternal market both formally and
inpractice? HowistheECbanenforced attheEC'sborders bothformally andinpractice? How
aretheconditions linked totheexceptions totheban(i.e.administration ofhormones for
therapeutic andzootechnical purposes) enforced, bothformally andinpractice, intheEC'sinternal
market andattheEC'sborders? What istheformal content andpractical effect oftheEC'scontrol
programme which ensures thatimported products donotreceive treatment more favourable than
domestic products?
6.202 Dr.André noted thatthisquestion wasnotrelated toscientific expertise. From apersonal
point ofview hebelieved thattheimportant number ofworkshops, international congresses (e.g.
Congress onAnabolizing Agents inGent:1992, 1993, 1994; Euroresidue Iin1990, Euroresidue II
in1993, Euroresidue IIIin1996), laboratory networks system, European research programmes, as
wellasthedevelopment ofQuality Assurance Systems inEurope hadtobeconsidered.
6.203 Dr.Arnold replied thatsinceitsentryintoforceCouncil Directive 86/469/EEC hadessentially
harmonised thecontrol ofresidues inliveanimals andmeat. Starting from1987, ECmember States
presented anannual updated national residue control planforapproval bytheCommission. Theresults
ofresidue controls werealsoreported totheCommission. TheDirective wasveryclearandrelatively
308Anderson andFesser (1996).
309Shih-Hsien Hsuetal.(1988).WT/DS48/R/CAN
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inflexible inwhatconcerned theidentification ofthesubstances andthespecies ofanimals tobechecked
andthenumber ofsamples tobetaken. Unfortunately, amajor partoftheanalytical capacities ofthe
laboratories oftheECmember States hadtobeusedregularly tomonitor substances which didnot
necessarily present therealproblem areas (e.g., thestilbene oestrogens).
6.204 Thescientific concept behind sampling, however, wasnotclearandwassubject todifferent
interpretations. Itseemingly mixed elements ofastatistically based monitoring system withother
concepts. Thereporting format wasonlysemi-quantitative withrespect tothereported residue contents
ofpositive samples. Inconsequence, theresults could notbeusedtocompare thesituation intheEC
member States or,forexample, toconduct acrude assessment ofexposure ofEuropean consumers
toresidues ofanabolic substances.
6.205 Dr.Arnold further explained thatanetwork ofreference laboratories hadrecently beenset
upwithanoutstanding European reference laboratory ontop.However, themoderate financial
contribution totheEuropean reference laboratories fromtheCommission wasgiven onlyonanannual
basis, leading todifficulties inensuring experienced permanent staffinthese institutes. Thequality
ofthenational reference laboratories co-ordinating theactivities oftheroutine laboratories carrying
outthedaily work could notbejudged. Although itwasnotknown howmany routine laboratories
were accredited nationally, itwasobvious thatsystems ofquality management hadnotyetbeen
established everywhere intheCommunity.
6.206 Theendogenous production intheanimals ofoestradiol-17 ,testosterone andprogesterone
causes difficulties inthecontrol oftheiruse. MRLs havenotbeenset,andcannot beset,forthe
therapeutic andzootechnical uses, because thedistribution ofthethree natural hormones inthethree
categories ofanimals (untreated animals, animals illegally treated forgrowth promotion, andanimals
legally treated forthepermitted purposes) largely overlap. Because withdrawal times could notbe
enforced onabroad scaleanddistribution chains wereinsufficiently controlled, onlylimited attempts
-requiring alotofman-power andother resources -could bemade toenforce compliance. Ifthere
wasasuspicion, ofcourse, theanimal involved canbetraced backandtheproducer questioned about,
e.g.,theprescription ofthedrug, theveterinarian involved etc.Themain difficulty wastoidentify
suspect animals inorder tostartfurther investigations andmeasures. Onlythediscovery ofaninjection
siteoranimplant containing illegal substances could provide proof ofatreatment. Decision limits
forthelevels ofoestradiol-17 hadprovisionally beenestablished inorder toidentify suspect animals.
6.207 Enforcement wasdifficult ifpeople didnotwanttocomply withthelegalrules-which otherwise
would perfectly guarantee consumer protection. Itappeared thatillegal anabolic hormones werereadily
available. Theexpectation ofextraprofits wasanincentive forthecontinued theuseofthesesubstances
includingbetaagonists,notonlyforfarmersbutalsoforparticipantsintheillegalnetworkofdistribution.
6.208 Dr.ArnoldrecalledthattherequirementsofDirective86/469/EECalsoappliedtothirdcountries
exporting liveanimals andmeattotheCommunity. Missions wereregularly senttothese countries
toevaluate theirsystems ofresidue monitoring andsurveillance. Attheborder, enforcement relied
entirely onthediscriminating power ofanalytical methods. Thiswasnotpossible inthecaseofmeat
fromanimals treated fortherapeutic orzootechnical purposes, because thismeatwasnotdifferent from
meatobtained fromanimals never treated ortreated withthesame substances forgrowth promotion.
Although domestically produced andimported products wereformally treated equally, thepossibility
ofdetectingillegalpracticesofgrowthpromotion(illegalreferringtonon-compliancewithEUlegislation,
nottouseswhich werealsoprohibited inthecountry oforigin) wasprobably significantly greater for
domestically produced meatbecause ofthepossibilities toinspect production plants withahistory of
non-compliance, totakesamples from liveanimals, etc.
6.209 Dr.Ritter indicated thathehadnoexpertise withregard toECenforcement, inrelation to
adiscussion about thenumber ofanimals checked peryearintheEuropean Communities andotherWT/DS48/R/CAN
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countries. However, henoted thatthenumber ofsamples taken could bemisleading. Theintent of
anymonitoring programme wasthedevelopment ofaprogramme thathadthestatistical confidence
necessary todetect violations totheextent thatthecompound wasused, toidentify residue levels which
wereoutofcompliance. Therelevant question waswhether themonitoring programme wasstatistically
confident andabletodetect compliance. Most monitoring programmes wereintended todetect a5per
centviolation rate95percentofthetime. Thenumber ofsamples thatwererequired todothatvaried
fromcountry tocountry andfromcommodity tocommodity because itwasafunction oftheusepractices
forthesubstances involved.
Question 24:
What analytical methods, orother technical means, ofresidue detection existtocontrol theuse
ofthesixhormones indispute forgrowth promotion purposes inaccordance withgood animal
husbandry practice and/or good veterinary practice. What means exist tocontrol theuseby
farmers ofthesixhormones indispute forgrowth promotion purposes inaccordance withgood
animal husbandry practice and/or good veterinary practice? What aretheir respective cost
implications?
6.210 Dr.André replied thatsincethesehormones wereprohibited within Europe, theircontrol was
included innational plans, theaimofwhich wastosurvey theirmisuse. Analytical methods were
available bothforscreening purposes andconfirmatory purposes. Forscreening purposes, several
methods hadbeendeveloped. Research wasalsocarried outtoprove theexogenous origin ofnatural
hormones, when detected inurine samples, based onmethods usedinhuman fordoping control. For
confirmatory purposes, different methods existed, withmostoftheavailable methods being based on
GC-MS detection andidentification. These techniques hadbeendeveloped formatrices likeurine,
fat,tissue, faeces orinjection sites.
6.211 Dr.Arnold noted thattheanalytical community oftheEuropean Communities wasveryactive.
Toprovide theappropriate methodology todetect illegal practices ofgrowth promotion -particularly
thepotentially hazardous practices involving black market drugs -wasagreatchallenge forthescientists
working inbothacademic andofficial laboratories. Asaresult, alarge number ofprobably valid -
although notalways validated -methods relying ondifferent principles wasavailable. Furthermore,
intheEuropean Communities itwaspossible toinspect farms andsample liveanimals, withthe
consequence offinesorlegalprosecution incaseofviolations.
6.212 Dr.McLean indicated thatdescriptions ofanalytical methods usewere published bythe
regulatory authorities ofmany countries. Control ofusebyfarmers wasdonethrough legislation which
detailed restrictions onthesale,possession anduseofthevarious hormonal preparations. Thecost
ofthesemeasures varied fromcountry tocountry andthecostofanalysis depends onthedruginquestion
andwhether screening orconfirmatory methods were employed.
6.213 Dr.Ritter responded thattheresidue detection methodology utilized tocontrol theuseofthe
sixgrowthpromotinghormonesgenerallyfollowedthoseproceduresdescribedinquestion22.Detection
methodologies forveterinary drugresidues were largely described bytwomain types ofanalysis
(Blanchflower, 1995). Screening methods generally hadahighsample throughout, permitting analysis
oflarge numbers ofsamples inarelatively short period oftime, andatminimal cost. They generally
hadalowprobability offalsenegatives andcould detect, butnotaccurately quantify, potentially positive
samples. Screening methods forthegrowth promoters were typically represented bytheradio
immunoassays.Incontrast,confirmatorymethodswereusedtoconfirmunequivocally,andtoquantitate,
thepresence ofadrugresidue. They werecharacterized byrelatively lowthroughput andhighcost
bothinterms ofequipment andsupplies, andalowprobability offalsepositives.WT/DS48/R/CAN
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6.214 Control ofveterinary drugs usedinfoodproduction byfarmers wasgenerally achieved by
national authorities through imposition ofregulations requiring thatdrugs ofthistypebedispensed
onlyonthewritten authority ofaproperly qualified veterinarian andincompliance withrelevant use
information established byappropriate national regulatory authorities. Compliance wasfurther assured
through rigorous monitoring and,where appropriate, through enforcement activity. Costimplications
generally related totheincreased costassociated withtherequirement thatsuch drugs onlybe
administered under theauthority ofaproperly qualified veterinarian. Costs would alsobeproportional
totherigour withwhich amonitoring andcompliance programme wasdesigned andimplemented.
Question 25:
What analytical methods, orother technical means, existtocontrol theuseofthesixhormones
indispute according totheconditions setoutintheproposal oftheECCommission in1984
(COM(84)295 final) andwhat aretheir respective costimplications?
6.215 Dr.AndrénotedthatthistwelveyearoldproposalhadbeenrejectedbytheEuropeanParliament.
6.216 Dr.Arnold recalled thatthisproposal hadenvisaged thecontrolled useofthethree natural
hormones forgrowth promotion andproposed re-visiting theprohibitions oftrenbolone acetate and
zeranol afterascientific evaluation ofthesesubstances. Inanalytical terms, theenforcement problems
would havebeensimilar tothose oftoday because residues inmeat remaining afterthe(proposed)
legalised usesforgrowth promotion would nothavediffered significantly from residues found after
illegal usesinmostcases. Thepharmaceutical industry could haveapplied formarketing authorization
ofstrictly formulated products, which would havebeenevaluated andapproved under theveterinary
medicines directives. There would havebeencompetition between high-quality, efficacious andsafe
products andproducts oftheblack-market. However, Dr.Arnold could notjudge whether thiswould
havelimited thegrowth ofthenowexisting black market, thereby reducing thecostsofenforcement.
6.217 Dr.McLean noted thatthemethods proposed inthatDirective weresimilar tothemethods
nowusedinother countries. However, thepassage oftimehadpermitted better analytical technology
andtechniques andincreased automation, oftenresulting inincreased laboratory throughput atdecreased
costpersample. Farmers were alsomuch better educated about theneedtoavoid residues which
exceeded theMRL. TheCommunity would nowbeinamuch better position toscreen forresidues
inmeatproducts thanitwasin1984.
Question 26:
Arethere other products (including veterinary drugs) commonly usedintheproduction ofmeat
andanimal products which havecomparable potential adverse effects onhuman oranimal health
asthesixhormones inquestion? Ifso,what analytical methods, orother technical means, of
residue detection existtocontrol their useinaccordance withgood animal husbandry practice
and/or good veterinary practices. What technical means exist tocontrol their usebyfarmers
inaccordance withgood animal husbandry practice and/or good veterinary practice? How do
thecostimplications forcontrolling theuseofthese other products differ from those usedtocontrol
theuseofthesixhormones inquestion?
6.218 Dr.André responded thattotheextent acompound wasactive asadrug, itcould exert toxic
effects. Drugs weresubmitted toregulation andwereregistered forprecise indications, under precise
conditions, including dataonMRLs anddefinition ofwithdrawal periods (seealsoresponse to
question 10). Several methods forcontrol were available. Drugs could onlyberegistered foruse
when amethod designed forresidue control existed. Networks oflaboratories andcontrol plans were
setupfordrugs according tothesame scheme astheoneusedforillegal drugs.WT/DS48/R/CAN
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6.219 Forproducts forwhich particular conditions ofusewere indicated, thecontrol wasusually
inthehands ofpractitioners. New recording systems were under development (seeresponse to
question 1).Controls byofficial bodies (e.g.Veterinary Inspection Services) wereeffective insome
countries. Inother countries regulations werechanging inorder toapply ECDirective 96/23, allowing
formore controls tobeperformed onthefarmitself. Thiswasparticularly trueforthehormones in
dispute, asforother banned compounds (chloramphenicol, rhonidazol, etc.).
6.220 Dr.Arnold indicated thatarather largenumber ofactive principles (probably afewhundred)
wereusedasveterinary drugs inoneorallcountries involved inthisdispute. Some substances were
soactive thattheirtherapeutic doses were aslowasmicrograms perkilogramme ofbody weight of
theanimal. Other substances wereusedinbothveterinary medicine andincropprotection, withsome
transfer ofresidues from animal feedviaproducts ofanimal origin tothehuman consumer.
Considerableprogresshadbeenmadetoregulatethesesubstancesonthebasisof"tolerances"forresidues
orMRLs. Many oftheunderlying ADIs hadbeenproposed byJECFA. More JECFA evaluations
hadindirectly beenappreciated andfound acceptance (e.g., intheMRL setting process within the
European Union) asonewould conclude from thelistofsubstances which hadformally passed the
elaboration process oftheCodex Alimentarius Commission.
6.221 IntheEuropean Communities, nonewactive principle hadbeenplaced onthemarket since
1992 unless aCommunity MRL hadbeenestablished under theprovisions ofregulation 2377/90.
Newanimaldrugapplicationshadtobeaccompaniedbyaproposedregulatorymethodsuitabletoenforce
tolerances/MRLs. Themainperformance characteristics (accuracy, precision, limitofdetection, limit
ofquantification,specificity)andtheruggedness,practicability,applicability,susceptibilitytointerference
ofthemethods were reviewed together withtheother documentation relating tothequality, safety
andefficacy ofthedrug.
6.222 Thereview oftheoldsubstances, however, wasstillongoing. Theevaluation oftheold
substances hadalsobegun inthepesticides sector. Themajority ofthese substances hadalonghistory
ofuses. Although theyhadnever beenevaluated according tocontemporary safety requirements, they
could probably beregarded assafeinthelightoftheexperience withthese substances. Should new
evidence indicate thathuman health hazards could arisefrom thepermitted usesofthese substances,
thecompetent authorities would withdraw therespective products untiltheproblems wereclarified.
There weresome examples, however, where highly efficacious substances withalonghistory ofuse
hadtobewithdrawn fromthemarket ofveterinary drugs forfoodanimals when more contemporary
standards wereapplied intheirre-evaluation (e.g., chloramphenicol, nitrofuranes, nitroimidazoles).
6.223 When oldsubstances werereviewed intheCommunity toestablish MRLs, theCommittee for
Veterinary Medicinal Products always considered theavailable analytical methodology. AnMRL was
notproposed ifnoanalytical method wasavailable. Thereview ofthemethods andinternational
harmonisation ofmethods suitable fortheenforcement ofCodex Standards wasconducted bythe
FAO/WHO Codex Committee forResidues ofVeterinary Drugs inFoods.
6.224 Themore difficult problem wastomonitor somany substances inallfoods ofanimal origin.
Thechemicalpropertiesofthesesubstancesweresodifferentthatitwasimpossibletoincludeallresidues
inafewmulti-residue methods. There weresubstances requiring special equipment fortheirdetection.
Itwasnotpractically feasible tomonitor allpotential residues inallfoodcommodities every year.
Themostreasonable approach wastocategorise compounds according topotential hazard andthelikely
exposure ofconsumers totheresidues. Some compounds required inclusion inresidue-monitoring
programmes every year; others might beselected forlonger cycles. Forafewcompounds, perhaps
nomonitoring wasnecessary. Directive 86/469/EEC covered veterinary drugresidues inmeat. Starting
in1988, ECmember States andcountries exporting meat totheCommunity hadtosubmit residue
control plans alsoforthese substances. ECmember States hadmore flexibility toadapt theplans to
theactual needs (e.g., areas ofrisk). Thenewlegislation adopted in1996enlarged thescope tocoverWT/DS48/R/CAN
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other foods thanmeat. Anincreasing number ofscreening testswerenowavailable which werebased,
e.g.onmicrobiological inhibition orimmunochemistry. These methods weresuitable toidentify suspect
"positives" (samples violating MRLs) andexhibit alowrateof"false-negative" results. However,
animportant aspect ofthecontrol of"good practices" wasthecontrol ofdistribution; distribution
ofveterinary drugs wasnotharmonised intheCommunity.
6.225 Dr.McLean replied thatmany products usedinanimal production hadthepotential tocause
adverse effects onhuman oranimal health. Thehazard wasidentified andmanaged through theuse
of"good practice", theapplication ofanMRL, residue surveys andlegalsanctions forviolations (see
alsoresponses toquestions 11,22and24).There wasnosignificant difference inthecostimplications
forcontrolling theuseofother veterinary drugs when compared withthehormones.
6.226 Dr.Ritterrepliedthattherewereavarietyofproducts,includingveterinarydrugsandpesticides,
which wereutilized intheproduction ofmeatandanimal products. Establishment ofMRLs forother
production aids,including bothveterinary drugs andpesticides, implied thatthese chemicals could
alsobeused essentially freeofpotential adverse effects inthehuman population, provided that
appropriate conditions hadbeenfollowed intheuseoftheproduction aid.Simply stated, onceMRLs
hadbeenestablished, adherence tointernationally accepted maximum limits implied thatallproducts
carry similar risks, ormore appropriately stated, asimilar lackofrisk,asdidthehormones atissue
inthisdispute.
6.227 Control ofusewasgenerally accommodated through appropriate control ofsale(restriction
ofusegenerally associated with“prescription ”drugs) andrigorous monitoring andcompliance
programmes, further supported byappropriate enforcement action. Inregard toanalytical methodology
available fordetection andmonitoring purposes, bothscreening andconfirmatory methods wereutilized.
Availability ofappropriate andreliable analytical methodology forother production aids, suchas
veterinary drugs, varied somewhat withthespecific agent andmight range fromdifficulties ofbound
residues withcarbadox andnitrofuran, tothespecial andimportant considerations which werenecessary
when assessing themicrobiological riskduetoresidues ofantimicrobial drugs infood.
Question 27:
What potential adverse effects onhuman health arise from theoccasional consumption ofmeat
containing residues inexcess oftheCodex MRL inthecaseofZeranol andTrenbolone?
6.228 Dr.André noted thatallofthepreviously described potential adverse effects onhuman health
mayarise. With regard totheirhormonal effects, thelower thefrequency andthelevelofresidue,
thesmaller istheriskofhealth hazards. Withregard totheirpotential carcinogenic effects, thefrequency
ofconsumption andthelevelofresidue wasnotofconcern.
6.229 Dr.Arnold indicated thatiftheresidues were duetotreatment oftheanimals andnotto
contamination ofthemeat andthemeat wasnotaninjection sitesothatthecauses oftheviolation
oftheMRLs were limited tobiological variability oftheanimals response totreatment; hedidnot
know ofanyspecific adverse effect onhuman health which could arisefromtheoccasional consumption
ofsuchmeatbecause ofnon-compliance withtheestablished conditions ofuse,andifthiswasasingle,
rareoroccasional event. Anysuchevent would, however, require regulatory action and-where
indicated -legalprosecution inorder toguarantee theintegrity ofthemargin ofsafety which hadbeen
found toberequired toensure themedium andlong-term protection oftheconsumers ’health.
6.230 Dr.Lucier responded thatitwould benecessary toconduct formal riskassessments toestimate
exposure-effect relationships following different levels ofexposure forthesixhormones. Inorder
tobeuseful, endpoints ofconcern needed tobedetermined (i.e., cancer, hormonal effects, etc.)and
doseresponse models applied and/or developed thatmade useofallavailable andrelevant information.WT/DS48/R/CAN
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Itmight benecessary toconduct additional research toputtheriskassessments onacredible scientific
foundation. Itshould benoted, however, thatonewould never haveallthescientific information needed
toremove alluncertainty inriskassessments. Priorities hadtobeagreed uponregarding which pieces
ofinformation aremost critical. Itwasalsoimportant tonotethatselection oftheriskassessment.
model could influence theresult. Threshold orlinear models might givedifferent results although
if"mimicking ofhormone effects" were determinative, thentheissue ofthreshold wasnotrelevant
sincephysiological levels ofthenatural hormone exceeded anythreshold thatmight exist(seeresponse
toquestion 8).Thesynthetic hormones could exert toxic effects notonlyrelated totheirhormone
action butalsobecause ofother structural/functional properties.
6.231 Dr.McLean observed thattheoccasional consumption ofmeat containing levels inexcess
oftheCodex MRL wasofnohealth concern. Thedegree ofexcess would needtobedefined, but
thetypeoftoxic response andNOEL would givesome guidance. Itmust beremembered thatthe
NOEL wasderived taking intoaccount studies involving administration foralifetime, withthelowest
effect levelbased onaresponse which could beasminor asabody weight change.
6.232 Dr.Ritter replied thatinviewofseveral assumptions inherent inthemodels utilized todevelop
MRLs, which overestimated safety (NOEL, application ofsafety factors, assumption thatMRL was
always present andthatdietary exposure toresidues would occur daily foranentire lifespan), itis
mostunlikely thatsignificant potential adverse effects onhuman health would arisefromtheoccasional
consumption ofmeat containing residues inexcess oftheCodex MRL forzeranol andtrenbolone.
Itwas,however, important tonotethatthepotential foradverse effects increased asafunction ofboth
thefrequency andexposure levelregarding consumption ofresidues inmeatinexcess oftheCodex
MRL forbothtrenbolone andzeranol.
Question 28:
Howwould youassess thefeasibility oflabelling withrespect tomeatproducts fromanimals treated
withgrowth-promoting hormones? How doesthiscompare withthefeasibility oflabelling in
other foodsafety contexts?
6.233 Dr.André indicated thatthisquestion wasnotrelated toscientific expertise, buttopolitical
decision. However, suchlabelling would beconsistent withthetraceability concept which wasrapidly
being improved inEuropean countries (ready tobeimplemented inFrance). However, thisimplied
thatanadequate control toqualify products would havetobeestablished; inthecaseofresidues of
hormones, detection inmeatdidnotstand inthewayoffeasible labelling.
6.234 Dr.Arnold saidthatinhisviewitwasnotfeasible tocontrol labelling, since itcould not
beconfirmed through laboratory testing whether ananimal hadeverbeentreated withgrowth promoters.
Iftheobjective wastoverify thatsomething hadnever beenused, e.g.,apesticide, thesituation was
similar. Thechances todetect food-irradiation, ontheotherhand, weremuch better. Also, ifgenetically
modified organisms wereinvolved infoodproduction, itwassometimes possible toroutinely detect
thealtered genetic material. There seemed tobenogenerally valid answer tothisquestion.
6.235 Dr.Lucier replied thatmeatproducts could belabelled toindicate thattheywerefromanimals
treated withgrowth-promoting agents sothatconsumers would haveasmuch information aspossible
todecide which meattobuy. Ifgrowth-promoting agents produced meatwithlower fatcontent, a
consumer withcardiovascular disease might specifically wanttobuymeatfrom agrowth-promoted
animal.
6.236 Dr.McLean observed thattheeffective labelling oftreated meatwould necessitate identification
oftheanimal atbirth, thefarm, sale,slaughter, processing andontotheconsumer. Thelogistics
oftheprocess would becomplex andmake itdifficult toregulate, especially inthecaseofprocessedWT/DS48/R/CAN
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meatproducts. Thecostwould faroutweigh anyperceived benefit. Thesame problem arose with
thefeasibility oflabelling other foods, butbecause ofthecomplex process formeatprocessing, itwas
much more expensive. Inhisview, themoney spent onsuchalabelling process would bebetter spent
onensuring microbiological safety offood. Food contaminated withmicrobes andtheirtoxins disabled
orkilled many people every year. Theadverse effects ofveterinary drugs oragricultural chemicals
wererarely reported, butreports offoodpoisoning frommicrobial contamination wereverycommon.
Forexample, arecent outbreak ofEscherichia colifoodpoisoning inScotland made 400people seriously
illandkilled 17,while asimilar outbreak inJapan infected 10,000 andkilled 11(Coghlan, A(1997)
NewScientist 153(2066)7).
6.237 Dr.Ritter replied thattheissueoflabelling offoodproducts wasthesubject ofintense public
debate, towhich there wasnoeasyresolution. Theissue withregard tothefeasibility oflabelling
inthecaseofthehormones could therefore relate asmuch totheobjective ofsuchastrategy asto
itsfeasibility.Useofthenaturalgonadalhormonesinmeatproductionproducedresiduelevelsconsistent
withthose which might typically beexpected inmeatproducts from untreated animals. Other than
tofulfil a"right toknow" objective, labelling inthiscasewould notappear toprovide information
ofvalue toconsumers inahealth related context. Particularly noteworthy wasthatasresidue levels
arecomparable inbothtreated anduntreated animals, andasexogenous hormones are,inanycase,
quantitatively andqualitatively indistinguishable fromthose endogenously present, itwasunlikely that
alabelling programme could beimplemented atanypractical level.
6.238 Inthecaseofthesynthetic hormones utilized ingrowth promotion, atleasttwohadbeen
subjected tointernational review andsaferesidue levels hadbeenrecommended. Thepurpose ofsuch
alabelling programme would beunclear given thataninternational review hadalready concluded that
residues atorbelow proposed levels didnotconstitute arisktoconsumers, evenunder theexaggerated
calculations andassumptions utilized inthedevelopment ofMRLs.
Questions 29-34 werefollow-up questions tothose presented earlier, andtheresponses tothefollow-
upquestions have been included withtheresponses totheearlier questions.
Question 35:
With reference totherapeutic andzootechnical useofthenatural hormones atissue, doyoubelieve
thattheECDirective 88/299 „ensures thatthere arenoresidues leftinmeat forhuman
consumption “(para 19,ECfirstsubmission intheCanadian complaint)?
6.239 Dr.Arnoldrepliedthatnosuchinsurancecanbegiven.Themeatwouldalwayscontainresidues
evenifwithdrawal times wereobserved. Theconcept of"noresidue" hadbeenlargely abandoned some
20years agowhen itbecame evident that"noresidue" wasafunction ofthelimitofdetection ofthe
analytical method. Allpermitted substances, including thehormones, wereregulated onthebasis of
an"acceptable residue" intheEEC. The"noresidue" concept stillapplied tobanned substances, but
thiswastrivial. Inthecaseofhormones itwasacceptable ifthesumofendogenous plusexogenous
hormones wasatorwithin physiological limits.
6.240 Theresponse ofDr.Ritter tothisquestion iscontained inhisresponse toquestion 20above.
VII. INTERIM REVIEW
7.1 On21May1997, theEuropean Communities andCanada requested thePanel toreview, in
accordance withArticle 15.2oftheUnderstanding onRules andProcedures Governing theSettlement
ofDisputes ("DSU"), theinterim report thathadbeenissued totheparties on7May1997. The
European Communities alsorequested thePanel toholdafurther meeting withtheparties todiscussWT/DS48/R/CAN
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thepoints raised initswritten comments andotherpoints which theywould develop during thatmeeting.
7.2 Wedecided toholdconcurrent interim review meetings withtheparties forboththisdispute
andtheparallel panel requested bytheUnited States. Thisdecision was,interalia,based onthe
similarities ofbothcases andthefactthattheinterim reports inbothcases onlydiffer inthedescription
ofthearguments oftheparties, whereas thesections dealing withthescientific experts andthelegal
findings inthetwocases arealmost identical. Inlightofthatdecision, andafterconsultations with
theparties involved, wealsodecided tomake acopyofthesections ofourinterim report dealing with
ourconsultation withscientific experts andourfindings, together withthecomments submitted inthat
regard bytheEuropean Communities andCanada, available totheUnited States. Byletter of3June
1997, theEuropean Communities objected tobothdecisions, arguing thattheyaffected dueprocess
anditsrights ofdefense and,consequently, itsrights andobligations under theWTO Agreement.
Itmade, however, nospecific claims ofprejudice. Since wecould notseehowtheEuropean
Communities could beprejudiced bythese decisions, werejected thisobjection.
7.3 Inaletter dated 23May1997, Canada requested ustorulethat,onthebasis ofArticle 15.2
oftheDSU, thediscussion attheinterim review meeting should belimited toonlythoseissues identified
intheparties 'written comments of21May1991. Byindicating thatitintended tosubmit itsspecific
comments onthePanel'sfindings andconclusions atsome timeinthefuture, Canada submitted that
theEuropean Communities hadfailed tostatetheprecise aspects ofthefindings andconclusions it
wished thePanel toreview initswritten comments of21May1997. Canada argued thattheintent
ofArticle 15.2oftheDSU isthatthepanel andparties arefullyaware ofissues toberaised atthe
interim review meeting sotheymayprepare andmake reasoned responses.
7.4 Article 15.2oftheDSU provides thefollowing:
"...Within aperiod oftimesetbythepanel, aparty maysubmit awritten request
forthepanel toreview precise aspects oftheinterim report prior tocirculation ofthe
finalreport totheMembers. Attherequest ofaparty, thepanel shallholdafurther
meeting withtheparties ontheissues identified inthewritten comments ..."(emphasis
added).
Itappeared tousthattheEuropean Communities, byonlyenumerating thenumbers oftheparagraphs
ofthefindings section ofourinterim report inrelation towhich ithasconcerns andnotstating inits
written comments theprecise aspects itwishes thePanel toreview, didnotrespect thewording of
Article 15.2oftheDSU. Weconsidered, however, thatthemain object andpurpose ofArticle 15.2
istomake surethattheother party isaware oftheissues which willberaised attheinterim review
meeting inorder toallow ittoprepare itsrebuttal. InlightofthefactthattheEC'swritten request
forreview ofthefindings section onlyrelated tofactual aspects, i.e.,thecorrect reflection oftheEC
arguments andthenames ofandreferences toindividual scientific experts, weconsidered thatCanada
would notbeunduly prejudiced byallowing theEuropean Communities topresent thesefactual points
attheinterim review meeting. We,therefore, decided thattheEuropean Communities could raise
these points ontheconditions thatitwould limititselftofactual issues andtotheparagraph numbers
ithadenumerated initswritten comments. Wenotethatthisdecision corresponds towhatCanada
requested initsletter of23May1997.
7.5 ThePanel metwiththeparties on4June1997 inorder toheartheirarguments concerning
theinterim report. Wecarefully reviewed thearguments presented bytheEuropean Communities
andCanada andtheresponses offered bybothsides.
7.6 TheEuropean Communities requested ustofindthatArticles 15.2and15.3oftheDSU and
thegeneral principle ofdueprocess prevent thePanel from modifying aspects oftheinterim report
onwhich theparties didnotsubmit comments. However, attheendoftheinterim review meetingWT/DS48/R/CAN
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theEuropean Communities appeared tomodify thisrequest byasking thePanel toreview itsfindings
inlightofthefactual comments made. Canada submitted thatattheinterim review stageapanel should
onlycorrect factual aspects andarguments made bytheparties and,asthecasemaybe,expand on
itsreasoning orfindings. According toCanada, itisinappropriate tochange, attheinterim review
stage, inanyfundamental wayanyofthemajor findings offactandlawwhich informed thePanel's
conclusion. Weconsidered thatnoprovision intheDSU limits ustoonlymodify those paragraphs
commented upon bytheparties ortoonlycorrect orslightly change factual elements orarguments.
Article 15.3oftheDSU onlyprovides that"[t]he findings ofthefinalpanel report shallinclude a
discussion ofthearguments made attheinterim review stage...".
7.7 TheEuropean Communities made twotypes ofcomments onthefindings section oftheinterim
report. Thefirstconcerned 20paragraphs inwhich theEuropean Communities isstated tohaveargued
oragreed tosomething which, according totheEuropean Communities, doesnotornotcompletely
reflect theEC'sposition taken during theproceedings. These comments related tothefollowing
paragraphs: 8.105, 8.109, 8.111, 8.112, 8.115, 8.131, 8.175, 8.176, 8.187, 8.190, 8.193, 8.204,
8.205, 8.213, 8.220, 8.224, 8.228, 8.232, 8.243 and8.274. Since these proposed changes concerned
therepresentation oftheEC'sownlegalorfactual arguments, weaccepted most ofthem.
7.8 Thesecond typeofcomments made bytheEuropean Communities related toparagraphs where
thephrase "thescientific experts advising thePanel" isusedwithout, according totheEuropean
Communities, citing thenames ofthescientists northeplace where theyhavemade thestatements
thePanel isinvoking. Italsoargued thatfrequently thereference provided doesnotreflect theviews
ofallthescientists. Canada recalled thatduring themeeting on17and18February 1997, thescientists
hadafullopportunity tocomment onandqualify eachother'sopinions andthat,therefore, silence
maybetaken toindicate acceptance orlackofrelevant knowledge ontheparticular issue. TheEuropean
Communities alsorequested ustoreview theaccuracy ofthefactual information contained inseveral
paragraphs. Wecarefully considered allthefactual comments thusmade and,where weagreed with
them, modified those paragraphs accordingly.
7.9 TheEuropean Communities andCanada alsorequested ustoinclude inthefinalreport the
procedural decisions taken bythePanel during thecourse ofitswork. Weadded these decisions in
anewSection Bonorganizational issues.
7.10 Canada submitted corrections ofitsownarguments andfactual elements andsuggested several
drafting changes, mostofwhich havebeentaken intoaccount inourfinalreport. Itargued, forexample,
thatitnever limited itsclaim under Article 5.5oftheSPSAgreement tothesubstances carbadox and
olaquindox. Thisremark isreflected anddealtwithinparagraph 8.174.
7.11 Both parties alsosuggested further changes oradditions inrespect oftheinterim reports '
descriptive sections which wetookintoaccount inre-examining thatpartofthereport. Inthiscontext,
theEuropean Communities requested ustoappend thetranscripts ofthejointmeeting withtheexperts
advising thePanel tothedescriptive partofthereport, arguing thatmany important statements made
bytheexperts inthesemeetings arenotreflected inSection 6oftheinterim report. Inorder toincrease
thetransparency ofourwork andtotakeintoaccount most ofthecomments made bytheEuropean
Communities onthedescriptive partoftheinterim report, wedecided toannex thetranscripts ofthe
jointmeeting withtheexperts of17-18 February 1997 toourfinalreport.WT/DS48/R/CAN
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VIII. FINDINGS
A. CLAIMS OFTHE PARTIES
8.1 Thisdispute arises essentially fromthefollowing facts. In1981 theCouncil oftheEuropean
Communities ("EC Council") adopted Directive 81/602/EEC310,interalia,requiring theECmember
States oftheEuropean Communities toprohibit theadministration tofarmanimals ofsubstances having
athyrostatic, oestrogenic, androgenic orgestagenic action. Directive 81/602/EEC further provided
thatpending adoption ofadecision oftheECCouncil ontheadministration tofarmanimals forgrowth
promotionpurposes311ofoestradiol-17,testosterone,progesterone,zeranolandtrenbolone312ECmember
States could continue toapply thenational regulations inforce concerning those substances.313In1988
theECCouncil adopted Directive 88/146/EEC314which brought theadministration tofarmanimals
forgrowth promotion purposes ofthese fivehormones within thegeneral prohibition imposed by
Directive 81/602/EEC. The1988 Directive alsorequired theprohibition ofimportation from third
countries ofanimals andofmeat from animals towhich substances withthyrostatic, oestrogenic,
androgenic orgestagenic action havebeenadministered.315Twoexceptions tothisgeneral banare
providedinDirective88/299/EEC316:(i)theadministrationfortherapeutictreatment317ofoestradiol-17,
testosterone, progesterone andsome oftheirderivatives; and(ii)theadministration forzootechnical
treatment318ofsubstances having anoestrogenic, androgenic orgestagenic action which areauthorized
inaccordancewithECDirectivesonveterinarymedicinalproducts.319On29April1996,theECCouncil
adoptedDirective96/22/EC320(repealingandreplacingDirectives81/602/EEC,
88/146/EEC and88/299/EEC) which confirms andextends theabove-mentioned prohibitions. This
1996 Directive willenter intoforce on1July1997.321
8.2 Canada claims thattheEuropean Communities, bybanning theimportation ofmeatandmeat
products from animals towhich anyofsixspecific hormones havebeenadministered forpurposes
ofpromoting thegrowth oftheanimals, hasacted inconsistently withtheAgreement ontheApplication
ofSanitary andPhytosanitary Measures ("SPS Agreement"), inparticular Articles 2,3and5;the
310ECOfficial Journal, L222, 7August 1981, p.32.
311Article 5ofDirective 81/602/EEC usestheterm"forfattening purposes". However, during thePanel proceedings
andinthisreport theterm "forgrowth promotion purposes" isused.
312Thefivehormones arethesubject ofthisdispute. Asixth hormone indispute, melengestrol acetate orMGA, falls
under thegeneral prohibition ofDirective 81/602/EEC andisaddressed inparagraph 8.4.
313Seepara. 2.2.
314ECOfficial Journal, L70,16March 1988, p.16.
315Seepara. 2.3.
316ECOfficial Journal, L128, 21May 1988, p.36.
317Therapeutic treatment means treatment ofadisease orother health problem.
318ZootechnicaltreatmentforthepurposesoftheECmeasuresindisputemeans,interalia,treatmentforthesynchronization
ofoestrus, termination ofunwanted gestation, theimprovement offertility andthepreparation ofdonors andrecipients for
theimplantation ofembryos (Article 2,paragraph 1(b)ofECDirective 88/299/EEC).
319Seepara. 2.4.
320ECOfficial Journal, L1125, 23May 1996, p.3.
321Seepara. 2.5.WT/DS48/R/CAN
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Agreement onTechnical Barriers toTrade ("TBT Agreement"); andtheGeneral Agreement onTariffs
andTrade 1994 ("GATT"), inparticular Articles IIIandXI.Canada alsoclaims that,eveniftheEC
measures indispute areconsistent withallofthese agreements, theapplication oftheECmeasures
atissueinanyevent nullifies orimpairs benefits accruing toCanada under theMarrakesh Agreement
establishingtheWorldTradeOrganization("WTOAgreement")withinthemeaningofArticleXXIII:1(b)
ofGATT.
8.3 TheEuropean Communities rejects these claims.
8.4 Thesixhormones indispute are: oestradiol-17 ,testosterone, progesterone, zeranol and
trenbolone (thefivehormones mentioned above which were brought within thegeneral prohibition
required byDirective 81/602/EEC byDirective 88/146/EEC) andmelengestrol acetate ("MGA"; a
sixth hormone falling under thegeneral prohibition ofDirective 81/602/EEC). Oestradiol-17 isa
natural hormone withoestrogenic action (i.e.,responsible forfemale characteristics); testosterone
isanatural hormone withandrogenic action (i.e.,responsible formalecharacteristics); progesterone
isanatural hormone withgestagenic action (i.e.,responsible formaintaining pregnancy); zeranol
isasynthetic hormone withoestrogenic action (which mimics theaction ofoestradiol-17 );trenbolone
isasynthetic hormone withandrogenic action (which mimics theaction oftestosterone); andMGA
isasynthetic hormone withgestagenic action (which mimics theaction ofprogesterone).322Natural
hormones arehormones which areproduced endogenously inanimals andhumans. Synthetic hormones
arehormoneswhichareartificiallyproduced.Oestradiol-17,testosteroneandprogesteronearehereafter
alsoreferred toasthethreenatural hormones; zeranol, trenbolone andMGA arehereafter alsoreferred
toasthethree synthetic hormones.
B. ORGANIZATIONAL ISSUES
1. Scientific evidence
8.5 Inthecourse ofthese proceedings, weconsidered several issues related tothegathering and
submission ofscientific evidence. These concerned theappointment ofscientific experts toadvise
thePanel, thedeadline forsubmission ofscientific evidence bytheparties tothedispute andarequest
bytheEuropean Communities toaskspecific national andinternational authorities toprovide thePanel
withscientific studies anddata.
8.6 Article 11.2oftheSPSAgreement provides thefollowing:
"Inadispute under thisAgreement involving scientific ortechnical issues, apanel
should seekadvice fromexperts chosen bythepanel inconsultation withtheparties
tothedispute. Tothisend,thepanel may, when itdeems itappropriate, establish
anadvisory technical experts group ,orconsult therelevant international organizations,
attherequest ofeither party tothedispute oronitsowninitiative" (emphasis added).
Article 13oftheDSU reads asfollows:
"1. Eachpanel shallhavetherighttoseekinformation andtechnical advice from
anyindividual orbodywhich itdeems appropriate ...
2. Panels mayseekinformation fromanyrelevant source andmayconsult experts
toobtain theiropinion oncertain aspects ofthematter. Withrespect toafactual issue
322Seeparas. 2.8-2.9.WT/DS48/R/CAN
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concerning ascientific orother technical matter raised byaparty toadispute, apanel
mayrequest anadvisory report inwriting fromanexpert review group .Rules forthe
establishment ofsuchagroup anditsprocedures aresetforthinAppendix 4"(emphasis
added).
8.7 Asoutlined above323,wedecided torequest theopinion ofexperts oncertain scientific and
other technical matters raised bytheparties tothisdispute. Forourexamination ofthisdispute, we
considered itmore useful toleave openthepossibility ofreceiving arange ofopinions fromindividual
experts onspecific scientific andtechnical questions, rather thantoestablish anexpert review group
which would havebeenrequired toreach aconsensus viewonthebasisofgeneral terms ofreference
given toitbythePanel. Weconsidered thatneither Article 11.2oftheSPSAgreement norArticle
13.2oftheDSUlimits ourrighttoseekinformation fromindividual experts asprovided forinArticle
11.2, firstsentence, oftheSPSAgreement andArticles 13.1and13.2, firstsentence, oftheDSU.
Theprocedures weadopted inthisrespect andtheviews expressed bytheexperts aresetoutin
paragraphs 6.1andfollowing.
8.8 After consultation withtheparties tothedispute (inaccordance withArticle 11.2ofthe
SPSAgreement), wedecided toseekadvice fromthesameexperts selected toadvise thepanel requested
bytheUnited States.324Weconsidered thistobeinlinewiththeobject andpurpose ofArticle 9.3
oftheDSU which provides thefollowing: "[i]fmore thanonepanel isestablished toexamine the
complaints related tothesame matter, tothegreatest extent possible thesame persons shallserve as
panelists oneachoftheseparate panels andthetimetable forthepanel process insuchdisputes shall
beharmonized".
8.9 Theprocedures weadopted forourconsultation withtheexperts andtheviews theyexpressed
aresetoutinparagraphs 6.1andfollowing. Itisofparticular importance thatwemade cleartothe
experts advising thePanel thatwewerenotseeking aconsensus position among theexperts butwanted
tohearallviews.325However, wealsopointed outatthemeeting withexperts that,inorder togain
time, where anexpert agreed withastatement made oranswer provided byanother expert, theformer
expert didnothavetotakethefloor.326Anyreference made inourfindings to"scientific experts advising
thePanel" (or"experts" or"scientific experts") refers tooneormore ofthefiveindividual experts
wethusappointed and,asthecasemaybe,theexpert sentbytheCodex Commission secretariat.
Thisphrase doesnotrefertonorincludes thescientists whowerepartofthedelegations oftheparties
tothisdispute. These arereferred tointhisreport byname, followed bythename ofthedelegation
ofwhich theywere part.
8.10 Withrespect tothesubmission ofscientific evidence bytheparties tothisdispute, wedecided
thattheycould submit written material onnewscientific evidence tosupport theirarguments byno
laterthan8February 1997. Wetookthisdecision inorder toensure thatboththeparties andthe
scientific experts advising thePanel would getanopportunity toexamine thescientific evidence before
the17-18 February meeting withtheexperts.
8.11 TheEuropean Communities alsorequested thatCanada provide thePanel theoriginals ofthe
studies andother relevant dataonwhich itscompetent authorities based thedecision toauthorize the
useofthehormones atissue. Italsoconsidered thattheoriginals ofthestudies andother dataonwhich
323Seeparas. 6.1ff.
324Theprocedures followed fortheappointment ofthese experts inthepanel requested bytheUnited States aswellas
theparties 'arguments inrespect oftheappointment oftheexperts inthisPanel aresetoutinparas. 6.3ff.
325SeeTranscripts ofthejointmeeting withexperts of17February 1997, p.14.
326Ibid.,p.20.WT/DS48/R/CAN
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the1988 JECFA Report based itsrecommendations should beprovided tothePanel. Asfarasthe
studies anddatausedbyCanadian authorities isconcerned, wedidnotconsider thisinformation to
berelevant toaddress theECmeasures indispute. Similarly, wedidnotconsider itnecessary torequest
thestudies anddataonwhich the1988 JECFA Report isbased since itwasourunderstanding that
bothparties involved inthisdispute participated intheelaboration ofthisreport.
2. Third party rights
8.12 Inthecourse ofourwork, weconsidered several issues related totheparallel existence of
thisPanel, requested byCanada, andthepanel requested bytheUnited States. Although different
panels, bothpanels relate tothesame ECmeasures, weredealtwithbythesame panel members and
wereassisted bythesame scientific experts. These issues relate toarequest bytheUnited States for
extended thirdparty rights, theorganization ofjointmeetings andtheaccess byparties inoneofthese
panels tomaterials submitted totheother panel.
8.13 Inthisrespect wenote,asageneral guideline, Article 9.3oftheDSU, which reads asfollows:
"Ifmore thanonepanel isestablished toexamine thecomplaints related tothesame
matter, tothegreatest extent possible thesamepersons shallserve aspanelists oneach
oftheseparate panels andthetimetable forthepanel process insuchdisputes shall
beharmonized "(emphasis added).
8.14 Initsthirdpartysubmission tothisPanel, theUnited States requested tobeallowed toparticipate
more fullyinourwork, i.e.,toreceive allthesubmissions oftheparties tothisdispute, toobserve
thewhole oftheproceedings atthesubstantive meetings ofthePanel withtheparties tothedispute
andwiththescientific experts andtomake abriefstatement atasuitable moment during thesecond
substantive meeting. TheUnited States based thisrequest onthestrong interest ithasinthisPanel's
review oftheECban,asdemonstrated bythesubmissions oftheUnited States tothepanel inthe
separate proceedings requested bytheUnited States. Itfurther argued thatsincebothpanels willdecide
ontheirreport ineachofthetwodisputes concurrently, thearguments andfactspresented inthis
proceeding canbeexpected tohaveasubstantial effect ontheinterests oftheUnited States intheseparate
proceeding itrequested. Insupport ofthisrequest, theUnited States alsoinvoked the(asoftoday
unadopted)PanelReporton"EuropeanCommunities-RégimefortheImportation,SaleandDistribution
ofBananas" where Canada andother thirdparties tothatdispute wereaccorded extended thirdparty
rights.327
8.15 Therights ofthirdparties aredealtwithinArticle 10andAppendix 3oftheDSU. Article 10
provides thatthird parties "shall haveanopportunity tobeheard bythepanel andtomake written
submissions tothepanel". Italsoprovides thatthirdparties areentitled toreceive thesubmissions
oftheparties made tothefirstsubstantive panel meeting. Paragraph 6ofAppendix 3specifies that
thirdparties shallbeinvited "topresent theirviews during asession ofthefirstsubstantive meeting
ofthepanel setaside forthatpurpose. Allsuchthirdparties maybepresent during theentirety of
thissession". Under priorGATT practice, moreexpansive rights weregranted tothirdparties inseveral
disputes.328Inthesecases, however, andcontrary tothesituation inthepresent dispute, parties agreed
totheextension ofsuchrights. InthePanel Report on"European Communities -Régime forthe
327Panel Report on"European Communities -Régime fortheImportation, SaleandDistribution ofBananas", circulated
on22May 1997, WT/DS27/R/USA, paras. 7.4-7.9.
328See,forexample, Panel Report on"Japan -Trade inSemiconductors", adopted on4May1988, BISD 35S/116, pp.116-
117,para. 5;Panel Report on"EEC -Import Regime forBananas", issued on11February 1994 (notadopted), DS38/R,
p.4,para. 8;Panel Report on"EEC -Member States 'Import Regimes forBananas", issued on3June1993 (notadopted),
DS32/R, p.2,para. 9.WT/DS48/R/CAN
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Importation, SaleandDistribution ofBananas", where noagreement between theparties ontheissue
existed, thepanel granted thefollowing extended thirdparty rights: itinvited thirdparties toobserve
thewhole ofthefirstsubstantive meeting andthesecond substantive meeting ofthepanel withthe
parties andgavethirdparties theopportunity tomake abriefstatement atasuitable moment during
thesecondmeeting.329Thepaneldidnotexpectthirdpartiestosubmitadditionalwrittenmaterialbeyond
theresponses tothequestions already posed during thefirstmeeting andrefused togrant further
participatory rights tothirdparties following thesecond substantive meeting, including participation
intheinterim review process.330
8.16 Having considered representations bytheUnited States, Canada andtheEuropean Communities
relating totheUSrequest forextended thirdparty rights, wedecided, prior toourfirstsubstantive
meeting withtheparties, nottoinvite theUnited States toobserve thatpartofthefirstmeeting normally
restricted toparties tothedispute. Thisdecision was,interalia,based onthefactthattheUSrequest
wasonlymade onedaybefore thefirstmeeting andthatthethird party rights oftheUnited States
withrespect toourfirstmeeting seemed tobesufficiently safeguarded bythenormal procedures as
setoutinArticle 10oftheDSU andparagraph 6ofAppendix 3.
8.17 However, considering thespecial status oftheUnited States inthiscase, asdemonstrated by
thefactthatitisthesolecomplainant intheparallel panel proceeding concerning thesameECmeasures
anddealt withbythesame panel members inaccordance withArticle 9.3oftheDSU, wedecided
asfollows withrespect tothethirdpartyrights oftheUnited States atourmeeting withscientific experts
andoursecond substantive meeting:
"(i) theUnited States willbeinvited toparticipate inthemeeting withscientific experts
tobeheldbythePanel requested byCanada;
(ii) thePanel reserves therighttoinvite theUnited States toattend thesecond substantive
meeting withtheparties".
8.18 Prior toourmeeting withscientific experts, wedecided toholdthatmeeting jointly forboth
thisPanel, requested byCanada, andtheparallel panel requested bytheUnited States. Thisdecision
stemmed fromthesimilarities ofthetwocases (thesame ECmeasures areatissueandbothcases are
dealtwithbythesame panel members), ourdecision tousethesame scientific experts inbothcases
andthefactthatwehadalready decided toinvite Canada andtheUnited States toparticipate inthe
meeting withscientific experts ineachofthetwocases. Inaddition, weconsidered that,fromapractical
perspective, there wasaneedtoavoid repetition ofarguments and/or questions atourmeetings with
thescientific experts. TheEuropean Communities objected tothisdecision arguing thatonejoint
meeting withtheexperts, instead oftwoseparate meetings, waslikely toaffect itsprocedural rights
ofdefence. Where itmade precise claims ofprejudice toitsrights ofdefence, wetookcorrective
action.331
8.19 Inview ofthatdecision, wealsodecided togiveaccess toalloftheinformation submitted
under eachpanel proceeding totheparties intheother panel proceeding, including theparties 'second
329Panel Report on"European Communities -Régime fortheImportation, SaleandDistribution ofBananas", op.cit.,
paras. 7.7and7.8.
330Ibid.,paras 7.8and7.9.
331TheEuropean Communities argued thatajointmeeting withexperts deprived itofitsright topresent itslegal and
scientific positions twice (afirsttimebefore thisPanel andasecond timebefore thepanel requested bytheUnited States).
Inlightofthisobjection wedecided thattheEuropean Communities would beallowed toaddress thejointmeeting twice
(afirsttimeafter theUnited States andasecond timeafter Canada). SeeTranscripts ofthejointmeeting withexperts of
17February 1997, paras. 1-2.WT/DS48/R/CAN
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written submissions, written versions oforalstatements andquestions raised bythePanel andtheparties,
andanswers thereto, ineachcase, aswellasallscientific documentation submitted bytheparties.
Bydoing so,weunderstood that,inthisPanel, wecould alsoconsider, where appropriate, thematerials
submitted before thepanel requested bytheUnited States.332TheEuropean Communities objected
tothisdecision arguing thatitwasmost likely going toaffect itssubstantive andprocedural rights
ofdefence. Itmade, however, nospecific claims ofprejudice. Weconsidered thatproviding all
information toallparties involved inbothpanels would increase thetransparency ofourwork, without
depriving parties oftheirsubstantive orprocedural rights, andisinlinewiththeobject andpurpose
ofArticle 9.3oftheDSU calling foraharmonization oftimetables ofbothpanels. Onthese grounds
werejected theEC'sobjection.
8.20 Prior tooursecond substantive meeting, wedecided toinvite theUnited States toobserve that
meeting withtheparties andtogrant ittheopportunity tomake abriefstatement attheendofthe
meeting. Thisdecision was,interalia,based onthefactthatoursecond meeting washeldtheday
afterourjointmeeting withthescientific experts andthattheparties tothisdispute would, therefore,
most likely comment on,anddraw conclusions from, theevidence submitted bythese experts tobe
considered inbothcases. Since inthepanel requested bytheUnited States thesecond meeting was
heldbefore thejointmeeting withscientific experts, weconsidered itappropriate, inorder tosafeguard
therights oftheUnited States intheproceeding itrequested, togrant theUnited States theopportunity
toobserve oursecond meeting inthiscaseandtomake abriefstatement attheendofthatmeeting.
C. GENERAL INTERPRETATIVE ISSUES
1. Scope ofthemeasures indispute
8.21 Canada contests theECbanonimports ofmeatandmeatproducts from cattle,treated with
anyofsixspecific hormones (oestradiol-17 ,testosterone, progesterone, zeranol, trenbolone andMGA)
forgrowth promotion purposes.333Canada doesnotchallenge theECbanonimports ofliveanimals ,
ofmeat andmeat products from animals other thancattle, from cattle treated withhormones other
thanthesixspecified ortreated withanyhormones forpurposes other thangrowth promotion.
8.22 Wefurther notethattheEuropean Communities argues thatitsimport banonliveanimals
towhich anyofthesixhormones havebeenadministered, isnecessary fortheprotection ofbothhuman
andanimal health.334However, theEuropean Communities doesnotmake thisargument withrespect
toitsimport banonmeatormeatproducts .Specifically, theEuropean Communities hasnotargued
thatitsimport banonmeatormeatproducts isnecessary fortheprotection ofanimal health either
inside oroutside theECterritory. Since theanimal health arguments invoked bytheEuropean
Communities exclusively relate toitsimport banonliveanimals andconsidering thattheECbanon
imports ofliveanimals treated withhormones hasnotbeenchallenged byCanada, andthusfallsoutside
332Thisdoes, ofcourse, notmean that,inthisPanel, Canada hasincorporated oragreed withthearguments submitted
bytheUnited States intheparallel panel itrequested orthatwehavetodeal, inthisPanel, withthearguments andclaims
submitted bytheUnited States intheother panel. Itonlymeans that,where weconsidered itappropriate, wewould be
abletoinvoke oraddress, inthisPanel, factual elements, scientific evidence orarguments submitted bytheEuropean
Communities ortheUnited States totheparallel panel requested bytheUnited States.
333Seepara. 3.1.
334Seepara. 3.6.WT/DS48/R/CAN
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thescope ofthisdispute, wefindthatwithin thescope ofthisdispute weneednottakeintoaccount
thearguments made bytheEuropean Communities which relate toanimal health.335
2. Application oftheSPSAgreement, theTBT Agreement andGATT
8.23 Canada invokes arguments relating tothree different agreements: theSPSAgreement, the
TBTAgreement andGATT. TheEuropean Communities, inturn,invokes thesamethreeagreements
initsdefense. Wenextexamine which ofthese agreements apply tothepresent dispute.
8.24 With respect totheSPSAgreement, bothparties agree thattheECmeasures indispute are
sanitary measures inthesense ofParagraph 1(b)ofAnnex AoftheSPSAgreement.336Paragraph
1(b)ofAnnex Adefines asanitary measure as
"anymeasure applied toprotect human oranimal lifeorhealth within theterritory
oftheMemberfromrisksarisingfromadditives,contaminants,toxinsordisease-causing
organisms infoods, beverages orfeedstuffs".
Footnote 4toAnnex Aspecifies that"contaminants" include, forthepurposes ofAnnex A,"pesticide
andveterinary drugresidues andextraneous matter". Since thesixhormones indispute areveterinary
drugs, theparties agree thatthealleged risksatissue arisefrom contaminants.
8.25 Weagree withtheparties thattheECmeasures indispute are"applied toprotect human ...
lifeorhealth" within theterritory oftheEuropean Communities fromrisksarising from"contaminants",
namely residues ofsixspecific hormones, infoods (according toparagraph 1(b)ofAnnex A).That
thecontested ECmeasures are,interalia,"applied toprotect human ...lifeorhealth" canbeinferred
fromthepreambles to,andlegislative history of,Directives 81/602/EEC and88/146/EEC.337Since
bothparties agree thatthecontested ECmeasures are"sanitary measures", weseenoneedtofurther
examine inthisdispute thedefinition ofmeasures "applied toprotect human ...lifeorhealth".
8.26 Bothparties alsoagree that,according toArticle 1.1oftheSPSAgreement, theSPSAgreement
isapplicable tothisdispute.338Article 1.1provides thattheSPSAgreement
"applies toallsanitary andphytosanitary measures which may, directly orindirectly,
affect international trade".
Weagree withtheparties thattheECmeasures "may, directly orindirectly, affect international trade".
Itcannot becontested thatanimport banaffects international trade.
8.27 With respect totheapplication ratione temporis oftheSPSAgreement totheECmeasures
indispute, wenotethattheSPSAgreement entered intoforce on1January 1995 (thedateofentry
intoforce oftheWTO Agreement ofwhich, according toArticle II:2ofthatAgreement, theSPS
Agreement isanintegral part). TheECmeasures indispute, however, were enacted before 1
335Ourfinding thatanimal health doesnotfallwithin thescope ofthisdispute does, ofcourse, notmean thatwecannot
takeintoaccount scientific evidence relevant forrisks tohuman lifeorhealth which isderived from studies ortestsapplied
toanimals.
336Seeparas. 3.1and3.7.
337Seeparas. 2.2-2.3.
338Seeparas. 4.23-4.25.WT/DS48/R/CAN
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January 1995 (namely 31July1981 and7March 1988), thusraising theissue ofwhether the
SPSAgreement applies tothese measures.
8.28 Article 3.2oftheDSUdirects ustoclarify theprovisions oftheSPSAgreement "inaccordance
withcustomary rulesofinterpretation ofpublic international law". According toestablished practice,
thefundamental rulesoftreaty interpretation setoutintheVienna Convention ontheLawofTreaties
("Vienna Convention") formpartofthese customary rulesofinterpretation.339Thegeneral principle
ininternational law,asembodied inArticle 28oftheVienna Convention, isthat"[u]nless adifferent
intention appears fromthetreaty orisotherwise established, itsprovisions donotbindapartyinrelation
to...anysituation which ceased toexistbefore thedateoftheentry intoforce ofthetreaty ..."
(emphasis added). TheECmeasures can,inthiscontext, beconsidered ascontinuing "situations"
which wereenacted before theentry intoforce oftheSPSAgreement butwhich didnotcease toexist
afterthatdate(contrary tothesituation envisaged inArticle 28).InlinewithArticle 28oftheVienna
Convention, theSPSAgreement should, therefore, inprinciple apply tothese ECmeasures, unless
anintention tothecontrary canbeestablished.340
8.29 Anexamination oftheSPSAgreement reveals nointention tothecontrary. Indeed, several
provisions oftheSPSAgreement confirm thegeneral principle thattheSPSAgreement should also
apply tosanitary measures which wereenacted before itsentry intoforce butwhich remain inforce
thereafter. Except forArticle 14which authorizes delays intheapplication ofsome orallofthe
provisions oftheSPSAgreement forleast-developed andother developing countries, notransition
periods areprovided for.ThefactthatArticle 14explicitly provides foratwo-year transition period
fordeveloping countries withrespect tosome oftheirexisting sanitary andphytosanitary measures,
confirms thattheSPSAgreement generally applies tomeasures enacted before theentry intoforce
oftheSPSAgreement butwhich aremaintained inforce afterthatdate. Thisisalsoconfirmed in
several provisions oftheSPSAgreement which explicitly address situations where Members "maintain"
asanitary orphytosanitary measure, suchasArticle 2.2("Members shallensure thatanysanitary ...
measure ...isbased onscientific principles andisnotmaintained without sufficient scientific evidence
..."), Article 3.3("Members mayintroduce ormaintain sanitary ...measures ...if..."), Article 5.6
("...when establishing ormaintaining sanitary ...measures ...Members shallensure that...")and
Article 5.8("...aspecific sanitary ...measure introduced ormaintained byanother Member ...").
8.30 Wefinally notethataccording toArticle XVI:4 oftheWTO Agreement, eachMember "shall
ensure theconformity ofitslaws, regulations andadministrative procedures withitsobligations as
provided intheannexed Agreements [including theSPSAgreement]". Thisprovision confirms that
measures which already existed asofthedateofentry intoforce oftheSPSAgreement alsoneedto
beconsistent withtherequirements imposed bythatAgreement.
8.31 Thus, wefindthattheSPSAgreement isapplicable tothisdispute.
339SeeAppellate Body Reports on"United States -Standards forReformulated andConventional Gasoline", adopted
on20May1996, WT/DS2/AB/R, pp.16-17 and"Japan -Taxes onAlcoholic Beverages", adopted on1November 1996,
WT/DS8/AB/R, pp.10-12.
340Werefer, inthisrespect, totheReports ofthePanel andAppellate Body on"Japan -Taxes onAlcoholic Beverages",
adopted on1November 1996 (WT/DS8/R andWT/DS8/AB/R), where boththePanel andtheAppellate Body applied GATT
(which entered intoforce on1January 1995) totheJapanese Liquor TaxLaw(of1953 andlastamended on1May1994),
eventhough thatJapanese measure hadbeenenacted andmostrecently beenamended before theentry intoforce ofGATT,
ontheimplicit ground thattheJapanese measure remained inforce afterthatdate. Thesame reasoning wasapplied inthe
Reports ofthePanel andAppellate Body on"United States -Standards forReformulated andConventional Gasoline", op.
cit.WT/DS48/R/CAN
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8.32 Inrespect oftheapplicability oftheTBTAgreement tothisdispute, wenotethatArticle 1.5
oftheTBTAgreement reads asfollows:
"Theprovisions ofthisAgreement donotapply tosanitary andphytosanitary measures
asdefined inAnnex AoftheAgreement ontheApplication ofSanitary and
Phytosanitary Measures".341
Since themeasures indispute aresanitary measures, wefindthattheTBTAgreement isnotapplicable
tothisdispute.
8.33 Wefinally notethatthisdispute relates totrade ingoods (incasuimports ofmeatandmeat
products) andthatonitsfaceGATT applies.342Inthiscontext, wenotethatCanada onlyinvokes GATT
afterhaving addressed theSPSAgreement andthattheEuropean Communities doesnotinvoke any
GATT provision other thanArticle XX(b) asajustification fortheECmeasures indispute.
3. Relationship between theSPSAgreement andGATT
8.34 Since boththeSPSAgreement andGATT apply tothisdispute, wenextexamine therelationship
between these twoagreements.
8.35 Thepartiestothedisputepresentdivergingviewswithrespecttowhetherweshouldfirstaddress
GATT ortheSPSAgreement. However, neither oftheparties claims thattherelevant provisions of
theSPSAgreement andGATT areinconflict. Therefore, wedonotneed, asapreliminary matter,
toaddress theGeneral Interpretative Note totheMultilateral Agreements onTrade inGoods which
onlyapplies "[i]ntheevent ofconflict between aprovision of[GATT] andaprovision ofanother
Agreement inAnnex 1A[interalia,theSPSAgreement]".
8.36 TheEuropean Communities makes adistinction between the"substantive" and"procedural"
provisions oftheSPSAgreement. According totheEuropean Communities, thesubstantive provisions
onlyinterpret Article XX(b) ofGATT343,without adding anynewobligations, while theprocedural
provisions contain requirements additional toGATT. Therefore, theEuropean Communities concludes,
the"substantive" provisions oftheSPSAgreement canonlybeaddressed ifrecourse ismade toGATT
Article XX(b), i.e.,if,andonlyif,aviolation ofanother provision ofGATT isfirstestablished. The
additional "procedural" provisions, ontheother hand, canbeexamined directly andindependently
ofaprior GATT violation.344
8.37 Canada argues thattheSPSAgreement isthelexspecialis forareview ofsanitary measures
andshould, therefore, beaddressed first. Canada claims thattheapplication oftheSPSAgreement
341Similarly, butlessexplicitly, Article 1.4oftheSPSAgreement provides that"[n]othing inthisAgreement shallaffect
therights ofMembers under theAgreement onTechnical Barriers toTrade withrespect tomeasures notwithin thescope
ofthisAgreement".
342Withrespect totheapplication ratione temporis ofGATT tothisparticular case, thesame reasoning andfindings apply
asthose developed fortheapplication ratione temporis oftheSPSAgreement inparagraphs 8.27 and8.28.
343Article XX(b) ofGATT reads asfollows: "Subject totherequirement thatsuchmeasures arenotapplied inamanner
which constitute ameans ofarbitrary orunjustifiable discrimination between countries where thesame conditions prevail,
oradisguised restriction oninternational trade, nothing inthisAgreement shall beconstrued toprevent theadoption or
enforcement byanycontracting party ofmeasures: ...(b)necessary toprotect human, animal orplant lifeorhealth".
344Seepara. 4.3.WT/DS48/R/CAN
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doesnotrequire aprior violation ofGATT since theSPSAgreement isa"free-standing" agreement
which applies toallsanitary measures andimposes requirements additional tothose inGATT.345
8.38 Inexamining therelationship between GATT andtheSPSAgreement, werecall thefundamental
rulesoftreaty interpretation setoutintheVienna Convention.346Article 31oftheVienna Convention
prescribes thatatreaty hastobeinterpreted "ingood faithinaccordance withtheordinary meaning
tobegiven totheterms ofthetreaty intheircontext andinthelightofitsobject andpurpose".347
8.39 Wefirstconsider thewording ofArticle 1.1oftheSPSAgreement which reads asfollows:
"This Agreement applies toallsanitary andphytosanitary measures which may,directly
orindirectly, affect international trade. Suchmeasures shallbedeveloped andapplied
inaccordance withtheprovisions ofthisAgreement".
According toArticle 1.1oftheSPSAgreement, tworequirements needtobefulfilled fortheSPS
Agreement toapply: (i)themeasure indispute isasanitary orphytosanitary measure348;and(ii)the
measure indispute may, directly orindirectly, affect international trade.349There arenoadditional
requirements. TheSPSAgreement contains, inparticular, noexplicit requirement ofapriorviolation
ofaprovision ofGATT which would govern theapplicability oftheSPSAgreement, asasserted by
theEuropean Communities.
8.40 WefurthernotethatthedistinctionproposedbytheEuropeanCommunitiesbetween"substantive"
and"procedural" provisions oftheSPSAgreement hasnobasisinthetextofthatAgreement andwould,
inanyevent, seem tobedifficult toapply tomost provisions contained therein. Forexample, the
obligation tobaseasanitary measure onariskassessment inaccordance withArticle 5ofthe
SPSAgreement includes bothsubstantive andprocedural elements.350
8.41 Moreover, wefindtheECclaim thattheSPSAgreement doesnotimpose "substantive"
obligations additional tothose already contained inArticle XX(b) ofGATT nottobepersuasive. It
isclearthatsome provisions oftheSPSAgreement elaborate onprovisions already contained inGATT,
inparticular Article XX(b). Thefinalpreambular paragraph oftheSPSAgreement provides, indeed,
thattheMembers desired "toelaborate rulesfortheapplication oftheprovisions ofGATT 1994which
relate totheuseofsanitary orphytosanitary measures, inparticular theprovisions ofArticle XX(b)".
Examples ofsuch rules are,arguably, some oftheobligations contained inArticle 2ofthe
SPSAgreement. However, onthisbasisalone wecannot conclude thattheSPSAgreement onlyapplies,
asArticle XX(b) ofGATT does, if,andonlyif,aprior violation ofaGATT provision hasbeen
established. Many provisions oftheSPSAgreement impose "substantive" obligations which go
345Seeparas. 4.1and4.4.
346Thelegal basis forthePanel toinvoke theVienna Convention isoutlined above inparagraph 8.28andfootnote 339.
347According toArticle 32oftheVienna Convention, recourse mayonlybehadtosupplementary means ofinterpretation
"inorder toconfirm themeaning resulting from theapplication ofArticle 31"orincaseArticle 31leaves themeaning
"ambiguous orobscure" orleads to"aresult which ismanifestly absurd orunreasonable".
348Asdefined inParagraph 1ofAnnex AoftheSPSAgreement, quoted anddiscussed inparas. 8.24 and8.25.
349Seepara. 8.26.
350Seeparas. 8.115 ff.WT/DS48/R/CAN
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significantly beyond andareadditional totherequirements forinvocation ofArticle XX(b).351These
obligationsare,interalia,imposedto"furthertheuseofharmonizedsanitaryandphytosanitarymeasures
between Members"352andto"improve thehuman health, animal health andphytosanitary situation
inallMembers".353They arenotimposed, asisthecaseoftheobligations imposed byArticle XX(b)
ofGATT, tojustify aviolation ofanother GATT obligation (such asaviolation ofthenon-discrimination
obligations ofArticles IorIII).
8.42 Wenoteinthisrespect thatthegeneral approach adopted inArticle XX(b) ofGATT is
fundamentally different from theapproach adopted intheSPSAgreement. Article XX(b), which is
notlimited tosanitary orphytosanitary measures, provides forageneral exception which canbeinvoked
tojustify anyviolation ofanother GATT provision. TheSPSAgreement, ontheother hand, provides
forspecific obligations tobemetinorder foraMember toenact ormaintain specific types ofmeasures,
namely sanitary andphytosanitary measures.
8.43 Theconclusion thattheSPSAgreement contains obligations which arenotalready imposed
byGATT isconfirmed inArticle 2.4oftheSPSAgreement which provides that"[s]anitary or
phytosanitary measures which conform totherelevant provisions ofthisAgreement shallbepresumed
tobeinaccordance withtheobligations oftheMembers under theprovisions ofGATT 1994 which
relate totheuseofsanitary orphytosanitary measures, inparticular theprovisions ofArticle XX(b)".
Indeed, topresume thatonesetofobligations (incasuGATT) ismetbecause another setofobligations
(incasutheSPSAgreement) hasbeenfulfilled, seems toimply thatthelatter setofobligations imposes
atleastasmany as,andprobably more obligations than, theformer. Support forthisconclusion is
alsofoundinArticle3.2oftheSPSAgreementwhichprovidesthat"[s]anitaryorphytosanitarymeasures
whichconformtointernationalstandards,guidelinesorrecommendationsshallbedeemedtobenecessary
toprotect human, animal orplant lifeorhealth, andpresumed tobeconsistent withtherelevant
provisions ofthisAgreement andofGATT 1994" (emphasis added). While bothagreements may
apply inagiven factual situation, theforegoing provision nonetheless establishes theSPSAgreement
asanagreement which imposes obligations which aredifferent from those imposed byGATT.
8.44 Wetherefore findthat,inaccordance withtheordinary meaning tobegiven totheterms of
theSPSAgreement intheircontext andinthelightofitsobject andpurpose (inconformity with
Article 31oftheVienna Convention), there isnorequirement, inanyoftheprovisions oftheSPS
Agreement, thatapriorviolation ofaGATT provision needbeestablished before theSPSAgreement
applies.
8.45 Having reached theconclusion thatwearenotperserequired toaddress GATT claims prior
tothose raised under theSPSAgreement, wemustthendecide which ofthetwoagreements weshould
examine firstinthisparticular dispute. TheSPSAgreement specifically addresses thetypeofmeasure
indispute. Ifwewere toexamine GATT first, wewould inanyevent need torevert tothe
SPSAgreement: ifaviolation ofGATT werefound, wewould needtoconsider whether Article XX(b)
could beinvoked andwould thennecessarily needtoexamine theSPSAgreement; if,ontheother
hand, noGATT violation werefound, wewould stillneedtoexamine theconsistency ofthemeasure
withtheSPSAgreement since nowhere isconsistency withGATT presumed tobeconsistency with
theSPSAgreement. Forthese reasons, andinorder toconduct ourconsideration ofthisdispute in
themost efficient manner, weshallfirstexamine theclaims raised under theSPSAgreement.
351Oneexample istheobligation contained inArticle 3.1oftheSPSAgreement which provides that"[t]o harmonize
sanitaryandphytosanitarymeasuresonaswideabasisaspossible,Membersshallbasetheirsanitaryandphytosanitarymeasures
oninternational standards, guidelines orrecommendations, where theyexist ...".
352Preambular para. 6oftheSPSAgreement.
353Preambular para. 2oftheSPSAgreement.WT/DS48/R/CAN
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D. THE SPSAGREEMENT
1. Overview oftheprovisions indispute
8.46 Canada claims violations ofArticles 2,3and5oftheSPSAgreement. Article 2elaborates
onthebasic rights andobligations ofMembers under theSPSAgreement. Article 3deals, more
specifically, withtheobjective ofharmonization ofsanitary measures onthebasis ofinternational
standards,guidelinesorrecommendations.Article5deals,inturn,withtheobligationofriskassessment
andthedetermination andapplication byMembers oftheirappropriate levelofsanitary protection.
8.47 Article 3.1requires Members tobasetheir sanitary measures oninternational standards,
guidelines orrecommendations except asotherwise provided forintheSPSAgreement, andinparticular
inArticle 3.3. Wenote, therefore, thatevenifinternational standards maynot,intheirownright,
bebindingonMembers,Article3.1requiresMemberstobasetheirsanitarymeasuresonthesestandards.
8.48 According toArticle 3.2sanitary measures which conform tointernational standards, guidelines
orrecommendations arepresumed tobeconsistent withboththeSPSAgreement andGATT. Weshall
therefore, asafirst step, examine whether there areinternational standards, guidelines or
recommendations withrespect totheECmeasures indispute and,ifso,whether theECmeasures are
based onthese standards, guidelines orrecommendations inaccordance withArticle 3.1.
8.49 Ifthere areinternational standards, guidelines orrecommendations andtheEuropean
Communities hasnotbased itsmeasures thereon, wewillneed, asasecond step,toexamine whether
theEuropean Communities canjustify itsmeasures under Article 3.3sinceArticle 3.1,which imposes
therequirement tobasesanitary measures oninternational standards explicitly refers toArticle 3.3
asproviding foranexception tothisrequirement.
8.50 Finally, ifthere arenointernational standards, guidelines orrecommendations withrespect
totheECmeasures indispute, ortosome ofthem, there would benostandards, guidelines or
recommendations forthese measures tobebased oninlinewithArticle 3.1.However, eveninthat
casetheconsistency oftheECmeasures indispute withArticles 2and5oftheSPSAgreement would
stillneedtobeexamined.
2. Burden ofproof
8.51 GiventhenatureofdisputesundertheSPSAgreement,whichimposessubstantiveandprocedural
requirements raising various, andinthiscasecomplex, issues offact,theallocation oftheburden of
proof isofparticular importance. Itinvolves consideration ofthewording, general outline andobject
andpurpose oftheSPSAgreement asawhole. We,therefore, firstexamine thisissueingeneral before
addressing thespecific burden ofproof foreachoftheprovisions indispute inmore detail below.
8.52 With respect toburden ofproof, Canada submits thatunder Article 3.8oftheDSU itisup
totheEuropean Communities torebut Canada 'sprima faciecase.
8.53 TheEuropean Communities argues thattheburden ofproof should restonthepartychallenging
theconsistency ofsanitary measures withtheSPSAgreement (incasuCanada). TheEuropean
Communities claims, interalia,thatitisuptoCanada toprovide evidence thattheuseofthehormones
indispute forgrowth promotion issafeandwithout risk.354
354Seepara. 4.65.WT/DS48/R/CAN
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8.54 Inaddressing theburden ofproof under theSPSAgreement, weconsider that,asisthecase
inmostlegalproceedings, theinitial burden ofproof restsonthecomplaining party inthesense that
itbears theburden ofpresenting aprima faciecaseofinconsistency withtheSPSAgreement. Itis,
indeed, fortheparty thatinitiated thedispute settlement proceedings toputforward factual andlegal
arguments inorder tosubstantiate itsclaim thatasanitary measure isinconsistent with the
SPSAgreement. Inother words, itisforCanada topresent factual andlegal arguments that,if
unrebutted, would demonstrate aviolation oftheSPSAgreement. Once suchaprima faciecaseis
made, however, weconsider that,atleastwithrespect totheobligations imposed bytheSPSAgreement
thatarerelevant tothiscase, theburden ofproof shifts totheresponding party.355
8.55 Inourview, theallocation ofevidentiary burden under theSPSAgreement totheMember
imposing asanitary orphytosanitary measure flows directly fromthewording ofmany oftheprovisions
contained inthatAgreement andinparticular thefirstthree words thereof:
"Members shall ensure that..." (e.g. Articles 2.2, 2.3, 5.1and5.6ofthe
SPSAgreement; emphasis added).
8.56 Moreover, thewording ofArticle 5.8(although thisprovision relates more totransparency
thantoanyrequirement oflegaljustification) further supports ourreading ofthisassignment ofburden
ofproof totheparty imposing themeasure:
"When aMember hasreason tobelieve thataspecific sanitary orphytosanitary measure
introduced ormaintained byanother Member isconstraining, orhasthepotential to
constrain, itsexports andthemeasure isnotbased ontherelevant international
standards, guidelines orrecommendations, orsuch standards, guidelines or
recommendations donotexist, anexplanation ofthereasons forsuchsanitary or
phytosanitary measure mayberequested andshall beprovided bytheMember
maintaining themeasure "(emphasis added).
8.57 Finally, wenotethatthisassignment ofburden ofproof totheparty imposing themeasure
isalsosupported byArticle 3.2which introduces apresumption ofconsistency withtheSPSAgreement
forsanitary measures which conform tointernational standards, guidelines orrecommendations.
Article 3.2states thefollowing:
355Twoprovisions oftheSPSAgreement do,however, explicitly confer theburden ofproof upon theexporting Member
(i.e.,theMember contesting thesanitary orphytosanitary measure), namely Article 4.1onequivalence andArticle 6.3on
pest- ordisease-free areas orareas oflowpestordisease prevalence. Thefactthatinthese instances theburden ofproof
isexplicitly conferred upon theexporting Member confirms thatunder other SPSprovisions theburden ofproof mayshift
totheMember imposing thesanitary orphytosanitary measure. Wenote, inthisrespect, theReport oftheAppellate Body
on"United States -Measures Affecting Imports ofWoven Wool Shirts andBlouses from India" (adopted on23May1997,
WT/DS33/AB/R) which addressed theissue ofburden ofproof under theAgreement onTextiles andClothing (the"ATC")
asfollows:
"...aparty claiming aviolation ofaprovision oftheWTO Agreement byanother Member must assert
andprove itsclaim. Inthiscase, India claimed aviolation bytheUnited States ofArticle 6oftheATC.
Weagree withthePanel thatit,therefore, wasuptoIndia toputforward evidence andlegal argument
sufficient todemonstrate thatthetransitional safeguard action bytheUnited States wasinconsistent with
theobligations assumed bytheUnited States under Articles 2and6oftheATC.India didsointhiscase.
And, withIndia having done so,theonus thenshifted totheUnited States tobring forward evidence
andargument todisprove theclaim. This, theUnited States wasnotabletodoand,therefore, thePanel
found thatthetransitional safeguard action bytheUnited States "violated theprovisions ofArticles 2
and6oftheATC" (pp.16-17).WT/DS48/R/CAN
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"Sanitaryorphytosanitarymeasureswhichconformtointernationalstandards,guidelines
orrecommendations shallbedeemed tobenecessary toprotect human, animal orplant
lifeorhealth, andpresumed tobeconsistent withtherelevant provisions ofthis
Agreement andofGATT 1994".
Introducing ageneral presumption ofconsistency withanagreement infavour ofaparty (incasuthe
party imposing themeasure) intheevent thatcertain conditions aremet,seems, indeed, topresuppose
thattheburden ofproof under thatagreement inprinciple (i.e.,incases where thesespecific conditions
arenotmet)restsonthatparty.
8.58 Wethusfindthat,forthepurposes ofthisdispute, Canada bears theburden ofpresenting a
prima faciecaseofinconsistency withtheSPSAgreement, afterwhich theburden ofproof shifts to
theEuropean Communities todemonstrate thatitsmeasures indispute meettherequirements imposed
bytheSPSAgreement.
3. Article 3.1: sanitary measures based oninternational standards
8.59 Article 3.1oftheSPSAgreement reads asfollows:
"Toharmonize sanitary andphytosanitary measures onaswideabasis aspossible,
Membersshallbasetheirsanitaryandphytosanitarymeasuresoninternationalstandards,
guidelines orrecommendations, where theyexist, except asotherwise provided for
inthisAgreement, andinparticular inparagraph 3".
Thefirstquestion wemustaddress iswhether there existany"international standards, guidelines or
recommendations" withrespect totheadministration ofanyofthesixhormones indispute forgrowth
promotion purposes. Forfoodsafety, thehealth concern atissue inthisdispute, paragraph 3(a)of
Annex AoftheSPSAgreement defines "international standards, guidelines orrecommendations" as
"thestandards, guidelines andrecommendations established bytheCodex Alimentarius
Commission relating tofood additives, veterinary drug andpesticide residues ,
contaminants, methods ofanalysis andsampling, andcodes andguidelines ofhygienic
practice" (emphasis added).
8.60 InlinewithArticle 3.1,weconsider thatifsuchCodex Alimentarius Commission standards,
guidelines orrecommendations ("Codex standards") existwithrespect totheadministration ofany
ofthesixhormones indispute forgrowth promotion purposes, asanitary measure taken byaMember
should either bebased onthese standards orbejustified under Article 3.3oftheSPSAgreement.
(a) Codex standards
8.61 Within thescope ofthemeasures indispute, wenotethatCodex standards existforfiveof
thesixhormones atissue (i.e.,forallhormones atissue other thanMGA).356Wewillaccordingly
examine thedefinition andscope ofapplication ofthese Codex standards anddetermine whether they
apply totheECmeasures indispute.
8.62 TheCodex Alimentarius Commission ("Codex"), aninternational body ofwhich mostWTO
Members (including Canada andthemember States oftheEuropean Communities) aremembers,
establishes, interalia,Acceptable Daily Intakes ("ADIs"), Maximum Residue Limits ("MRLs") and
other recommendations forveterinary drugs. Itdoessoonthebasis oftheadvice oftheCodex
356Seepara. 2.20, 2.21 and2.23.WT/DS48/R/CAN
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Committee onResidues ofVeterinary Drugs inFoods andtherecommendations oftheJointFAO/WHO
Expert Committee onFood Additives ("JECFA"). While Codex iscomposed ofgovernment
representativesofmemberStates,JECFAiscomposedofindependentscientists.JECFAmakesscientific
evaluations andrecommendations; Codex takes thedecision whether ornottoadopt these
recommendations. However, onceadopted Codex recommendations are,according totheGeneral
Principles ofCodex, notbinding upon Codex members. They areonlyofanadvisory nature. The
procedures tobefollowed toadopt aCodex recommendation havebeenoutlined above.357
8.63 ThegoalofJECFA 'sevaluation ofveterinary drugs is
"toestablish safelevels ofintake bysetting Acceptable Daily Intakes (ADIs) andto
develop maximum residue limits when veterinary drugs areusedinaccordance with
good veterinary practice" (emphasis added).358
Theterm"good veterinary practice" (aswellastheterm"good animal husbandry practice" often used
inJECFA Reports) isforCodex purposes, according totheCodex expert advising thePanel359,a
synonym forwhatisknown inCodex terminology as"Good Practice intheUseofVeterinary Drugs"
("GPVD"; hereafter alsoreferred toas"good practice"), inturndefined as
"theofficial recommended orauthorized usage including withdrawal periods, approved
bynational authorities, ofveterinary drugs under practical conditions".360
8.64 AnADIsetbyCodex is"anestimate byJECFA oftheamount ofaveterinary drug, expressed
onabodyweightbasis,thatcanbeingesteddailyoveralifetimewithoutappreciablehealthrisk(standard
man=60kg)"(emphasis added).361ThisADIisderived fromtheexperimental noobservable effect
levelinthemostappropriate animal species, byapplying anappropriate safety factor. ACodex MRL,
ontheother hand, ifimplemented innational law,determines theamount ofresidues which islegally
permitted orrecognized asacceptable infoodandisprimarily aregulatory tooltoensure thatintake
doesnotexceed theADIandthatgoodpractice isobserved. ACodex MRL isfrequently setatlevels
below (even farbelow) thetheoretical safelevels determined fromanADI. Codex MRLs forveterinary
drugs arenormally expressed inµg/kg onafresh weight basis inmeat.362
8.65 With respect tothethree natural hormones indispute, oestradiol-17 ,progesterone and
testosterone (classified byCodex as"veterinary drugs"), similar Codex standards apply. Forallthree
hormones, when usedforgrowth promotion purposes, itwasconsidered "unnecessary" toestablish
anADIorMRL. Forallthree hormones thefollowing footnote explained theword "unnecessary":
"Establishing anADIandan[MRL] forahormone thatisproduced endogenously at
variablelevelsinhumanbeingswasconsideredunnecessarybytheCommittee.Residues
357Seeparas. 2.15-2.16.
358Seepara. 2.14.
359Seepara. 2.19.
360Ibid.
361Seepara. 2.17.
362Seepara. 2.18.WT/DS48/R/CAN
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resulting fromtheuseofthissubstance asagrowth promoter inaccordance withgood
animal husbandry practice areunlikely toposeahazard tohuman health".363
The32nd JECFA Report of1988, onwhich theCodex standards arebased, concluded forallthree
natural hormones administered forgrowth promotion purposes thattheresidue levels ofeachofthese
hormones when found inmeatfromanimals treated withimplants according togoodanimal husbandry
practice areextremely lowwhen compared withtheamounts endogenously produced daily inhuman
beings ornormally present inthedairy products ortissues ofuntreated animals orother foods.
According toJECFA, thepotential toxiceffect ofresidues ofthesehormones isdirectly related totheir
hormonal effect. Since theadditional residue levels intreated animals havenohormonal effect, the
Report concluded thatthese residue levels arenotcapable ofexerting anytoxiceffect. JECFA further
noted thatthetotalresidue levels intreated animals fallwellwithin thenormal range oflevels found
inuntreated animals ofdifferent types andages. Onthebasis ofthissafety assessment andinview
ofthedifficulty ofdetermining thelevels ofresidues attributable totheuseofthishormone asagrowth
promoter incattle (residues ofendogenous natural hormones inmeat cannot, according toJECFA,
bepractically distinguished from those exogenously administered), JECFA concluded thatitwas
"unnecessary" toestablish anADIorMRL forthese hormones.364
8.66 Withrespect totwoofthethreesynthetic hormones atissue, zeranol andtrenbolone (classified
byCodex as"veterinary drugs"), thefollowing Codex standards apply: anADIof0-0.5 and0-0.02
µg/kg bodyweight, respectively, andanMRL of2µg/kg -trenbolone inbovine muscle and10µg/kg
-trenbolone inbovine liver.365
8.67 The32nd JECFA Report of1988, onwhich theCodex standard forzeranol isbased, noted
thatzeranol wasshown tobeaweak oestrogen which mimics theaction ofoestradiol-17 .TheReport
concluded thatthetoxic (incasutumorigenic) effect ofzeranol isassociated withitshormonal (i.e.,
oestrogenic) properties andthatanADIcould thusbeestablished onthebasisofano-hormonal-effect
level. Adopting what itconsidered tobeaconservative approach byusing asabasis studies on
ovariectomized female cynomolgus monkeys (highly sensitive tooestrogenic substances) andusing
asafety factor of100,JECFA setanADIforhuman beings of0-0.5 µg/kg ofbody weight. Fora
70kgperson consuming 500gofmeatdailyoveranentire lifetime, themaximum permissible orsafe
level ofzeranol residues inmeat would then, according toJECFA, be70µg/kg ofedible tissue.
However, theReport noted thatwhen zeranol isadministered tocattle according totheproposed good
practice, themaximum mean residue levels would notexceed 0.2µg/kg inmuscle and10µg/kg in
liveratanytimeafterimplantation (irrespective ofthewithdrawal period respected). These residue
levels obtained onthebasisofgoodpractice arethusfarbelow whatJECFA determined tobethesafety
levelof70µg/kg. However, inorder tosetalevelwhich isdetectable byusing methods available
forroutine residue analysis, theofficial Codex MRL wasincreased to2µg/kg inmuscle andsetat
10µg/kg inliver.366
8.68 Trenbolone acetate isthechemical form oresterusedfortheadministration oftrenbolone .
Trenbolone, ortrenbolone acetate ("TBA"), anandrogen which mimics theaction oftestosterone, is
rapidly hydrolysed afteradministration tocattle, themajor metabolites (i.e.,compound intowhich
TBAbreaks down bychemical activity when entering thebody) being -trenbolone, occurring, inter
363Seepara. 2.21
364Seepara. 2.22.
365Seepara. 2.23.
366Seepara. 2.24.WT/DS48/R/CAN
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alia,inliver, and-trenbolone, present inmuscle.367With respect toTBA, the32ndJECFA Report
of1988 concluded thatitspotential toxic effects onlyariseasaconsequence ofitshormonal activity
andconcluded that,therefore, anADIcould beestablished onthebasisofano-hormonal-effect level.368
Adopting what itconsidered tobeaconservative approach byusing asabasis studies oncastrated
malerhesus macaque monkeys which arehighly sensitive tocompounds withantigonadotropic activity
andpigswhich areasensitive model forassessing hormonal effects ofTBAandusing asafety factor
of100,JECFA latersetanADIforhuman beings of0-0.02 µg/kg ofbodyweight (34th JECFA Report
of1989).369Themaximum ADIfora60kgperson would thusbe1.2µgofTBAresidues. JECFA
thensetMRLsfor-trenboloneinmuscleand-trenboloneinliverof2µg/kgand10µg/kgrespectively,
based onaverage residue levels inheifers at15-30 daysafterimplantation of300mgTBA, noting
thatconcentrations would evenbelower attheproposed good practice. According toJECFA, the
MRLs thusobtained onthebasis ofconservative estimates would notexceed theCodex ADIorsafe
levelatanytimeafterimplantation ofthedrug(irrespective ofthewithdrawal period respected).
8.69 TheEuropean Communities argues thattheCodex standards outlined above arenotrelevant
tothisdispute. Itargues thatthere arenoCodex standards fortheuseofhormone growth promoters,
onlyCodex standards formaximum residue levels andthatsince theECmeasures indispute donot
setmaximum residue levels, there existnoCodex standards onwhich theECmeasures needtobe
based. Moreover, theEuropean Communities argues, theCodex standards invoked arelevels of
protection, notmeasures ,andsince there isnoobligation intheSPSAgreement toadopt Codex
recommendedlevelsofprotection,thestandardsinvokedareirrelevantfortheECmeasuresindispute.370
8.70 TheEuropean Communities alsonotes thatthedecision byCodex (ofJuly1995) toformally
adopt thefiveCodex standards atissue wastaken byamajority ofonly33votes infavour, 29votes
against and7abstentions; averyclose votewhich isunusual inCodex practice where proposals are
normally adopted byconsensus, indicating thattheissue ofhormone growth promoters hasbeenand
continues tobeverycontroversial.371
8.71 TheEuropean Communities finally argues thattheprocess which ledtotheadoption ofthe
Codex standards started longbefore theentry intoforce oftheSPSAgreement andwasonlycompleted
sixmonths afterthatdate. Atthetimethestandards werediscussed, Codex members were, therefore,
according totheEuropean Communities, unaware ofthefactthattheCodex standards, which within
theCodex system areonlyofanadvisory nature, would inthefuture become "binding" byvirtue of
theSPSAgreement.372TheEuropean Communities seems toconsider thiselement asareason to
disregard these Codex standards inthisdispute.
8.72 Inconsidering these ECarguments, wenotethatArticle 3.1unambiguously prescribes that
"...Members shallbasetheirsanitary ...measures oninternational standards ...where theyexist..."
(emphasis added). Paragraph 3ofAnnex AoftheSPSAgreement states equally clearly thatthe
international standards mentioned inArticle 3:1are"forfoodsafety, thestandards ...established by
theCodex Alimentarius Commission relating to...veterinary drug...residues ..."(emphasis added).
Noother conditions areimposed intheSPSAgreement ontherelevance ofinternational standards
367Seepara. 2.25.
368Ibid.
369Seepara. 2.25.
370Seepara. 4.66.
371Seepara. 4.209.
372Seepara. 4.92 andECsubmissions tothepanel considering theUScomplaint onthesame measures.WT/DS48/R/CAN
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forthepurposes ofArticle 3.Therefore, asapanel making afinding onwhether ornotaMember
hasanobligation tobaseitssanitary measure oninternational standards inaccordance withArticle 3.1,
weonlyneedtodetermine whether suchinternational standards exist. Forthese purposes, weneed
notconsider (i)whether thestandards reflect levels ofprotection orsanitary measures orthetypeof
sanitary measure theyrecommend, or(ii)whether these standards havebeenadopted byconsensus
orbyawideornarrow majority, or(iii)whether theperiod during which theyhavebeendiscussed
orthedateoftheiradoption wasbefore oraftertheentry intoforce oftheSPSAgreement.373
8.73 WenotethatthefiveCodex standards outlined above arestandards relating toveterinary drug
residues asrequired inparagraph 3(a)ofAnnex A374andapply exclusively withrespect tocattle and
meatandmeatproducts ofbovine origin andwithrespect tofiveofthesixhormones indispute when
these hormones areusedforgrowth promotion purposes.375Werecall thescope oftheECmeasures
indispute, inparticular thattheyarelimited totheECbanonimports ofmeatandmeatproducts of
bovine origin fromcattle treated withanyofsixspecific hormones ifthetreatment withanyofthese
substances iscarried outforgrowth promotion purposes.376Wefind, therefore, thatinternational
standards existwithrespect totheECmeasures indispute, totheextent theyrelate tofiveofthesix
hormones atissue (allbutMGA), inthesense ofArticle 3.1andparagraph 3(a)ofAnnex A.We
mustnextdetermine whether theECmeasures arebased onthese international standards interms of
Article 3.1.
(b) Sanitary measures based onCodex standards
8.74 Canada argues thattheECmeasures forzeranol andtrenbolone arebased onMRLs ofzero
andare,therefore, notbased ontheCodex MRLs. Canada further claims thatfullacceptance ofthe
Codex MRLs forresidues ofveterinary drugs infooddictates thatdistribution offoodconforming
withtheMRLs willnotbehindered bylegalprovisions. Since theECmeasures indispute prohibit
thedistribution ofbeeftreated withanyofthefivehormones forwhich Codex standards existforgrowth
promotion purposes, Canada concludes thattheEuropean Communities hasnotaccepted theCodex
MRLs andhasthusnotbased itsmeasures onthem.377TheEuropean Communities doesnotsubmit
thatitsmeasures arebased ontheCodex standards, butrather argues that,asdiscussed above378,there
arenorelevant Codex standards onwhich itsmeasures indispute needtobebased.
(i) Themeaning ofbased on
8.75 TheSPSAgreement doesnotexplicitly define thewords based onasusedinArticle 3.1.
However, Article 3.2,which introduces apresumption ofconsistency withboththeSPSAgreement
andGATT forsanitary measures which conform tointernational standards, equates measures based
oninternationalstandardswithmeasureswhichconformtosuchstandards.Article3.3,inturn,explicitly
relates thedefinition ofsanitary measures based oninternational standards tothelevel ofsanitary
protection achieved bythese measures. Article 3.3stipulates theconditions tobemetforaMember
373Werecall inthisrespect thattheCodex standards indispute haveinanyevent beenadopted inJuly1995, i.e.,subsequent
totheentry intoforce oftheSPSAgreement on1January 1995. With respect tothetimeframe fortheapplication ofthe
SPSAgreement ingeneral, werefer toparagraphs 8.27-8.30.
374Seepara. 8.59.
375Seepara. 2.20.
376Seepara. 8.21.
377Seepara. 4.64.
378Seeparas. 8.69-8.72.WT/DS48/R/CAN
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toenact ormaintain certain sanitary measures which arenotbased oninternational standards.379It
applies more specifically tomeasures "which result inahigher levelofsanitary ...protection than
would beachieved bymeasures based ontherelevant international standards" ormeasures "which
result inalevelofsanitary ...protection different from thatwhich would beachieved bymeasures
based oninternational standards". Oneofthedetermining factors indeciding whether ameasure is
based onaninternational standard is,therefore, thelevelofprotection thatmeasure achieves. According
toArticle 3.3allmeasures which arebased onagiven international standard should inprinciple achieve
thesame levelofsanitary protection. Therefore, ifaninternational standard reflects aspecific level
ofsanitary protection andasanitary measure implies adifferent level, thatmeasure cannot beconsidered
tobebased ontheinternational standard.
8.76 Wefind, therefore, thatforasanitary measure tobebased onaninternational standard in
accordance withArticle 3.1,thatmeasure needs toreflect thesame levelofsanitary protection asthe
standard .380Inthisdispute acomparison thusneeds tobemade between thelevelofprotection reflected
intheECmeasures indispute andthatreflected intheCodex standards foreachofthefivehormones
atissue.
8.77 Without limiting thepossibilities ofhowalevelofprotection maybeexpressed foraparticular
substance, weconsider thatinthespecific fieldofveterinary drugs (including thesixhormones atissue),
alevel ofprotection canbedirectly linked totheamount ofresidues ofthatdrugallowed either to
beingested byhumans onadaily basis ortobepresent inaparticular food.381Alevelofprotection
canthus, interalia,beexpressed bywayofsetting amaximum amount ofresidues allowed fordaily
intake byhumans overalifetime (often defined asacceptable daily intake orADI382)and(or)byway
ofadopting amaximum amount ofresidues allowed tobepresent inaparticular food(often defined
asmaximum residue limitorMRL383).However, thefactthatanADIorMRL canreflect alevelof
protection (without stricto sensu itself being alevelofprotection), doesnotexclude, astheEuropean
Communities hasargued, thatanADIorMRL canalsobeasanitary measure inthesense ofthe
SPSAgreement.
(ii) Comparison oflevels ofsanitary protection
8.78 Inthisdispute, twooftheinternational standards applicable, namely theCodex standards with
respect tozeranol andtrenbolone (twosynthetic hormones), provide foranADIof0-0.5 and0-0.02
µg/kg ofbodyweight, respectively, andanMRL of10µg/kg forbovine liverand2µg/kg forbovine
muscle forzeranol andanMRL of10µg/kg -trenbolone forbovine liverand2µg/kg of-trenbolone
forbovine muscle.384These ADIs andMRLs reflect thelevelofprotection setbytheCodex standards.385
379Article 3.1explicitly refers toArticle 3.3asproviding forexceptions tothegeneral obligation tobasesanitary measures
oninternationalstandards:"...Membersshallbasetheirsanitary...measuresoninternationalstandards...,exceptasotherwise
provided forinthisAgreement, andinparticular inparagraph 3"(emphasis added).
380Werecall, however, that,given theexceptions provided forinArticle 3.3,therequirement thatasanitary measure
reflects thesame level ofprotection astherelevant international standard isinnowayabsolute. Thisrequirement isonly
imposed forameasure tobebased onsuch international standard inaccordance withArticle 3.1.
381Theconcept of"appropriate" level ofprotection isexamined inparagraph 8.82.
382Seeparas. 8.62 ff.
383Ibid.
384Seeparas. 2.23-2.25
385Seepara. 8.77.WT/DS48/R/CAN
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Todetermine whether theECmeasures indispute withrespect tozeranol andtrenbolone arebased
onthese Codex standards, weneedtoexamine whether thelevel ofprotection reflected intheEC
measures isthesame asthelevelofprotection expressed bytheCodex standards.386Since theEC
measures indispute donotallow thepresence ofanyresidues ofthese twohormones inanymeator
meatproduct oranyofthese residues tobeingested byhumans (imposing whatitcallsa"noresidue"
level), thelevelofprotection reflected intheECmeasures issignificantly different fromthelevelof
protection setbytheCodex standards (a"noresidue" levelasopposed toanADIofmaximum 0.5
and0.02µg/kg ofbody weight andanMRL of2and10µg/kg for,respectively, bovine muscle and
bovine liver). TheECmeasures indispute, inasfarastheyrelate tozeranol andtrenbolone, are,
therefore, notbased onexisting international standards asspecified inArticle 3.1.
8.79 When establishing theother three Codex standards applicable totheECmeasures indispute,
Codex considered it"unnecessary" tosetanADIorMRL forresidues ofoestradiol-17 ,testosterone
andprogesterone(thethreenaturalhormones).387Theamountofresiduesofthesehormonesadministered
forgrowth promotion purposes allowed bythese Codex standards is,therefore, inanyevent higher
thanzero(amaximum levelofsuchresidues hasnotevenbeenprescribed; thislevelishereafter referred
toasan"unlimited residue level"). TheECmeasures indispute, ontheother hand, donotallow the
presence ofanyresidues ofthese three hormones administered forgrowth promotion purposes (again
imposing whattheEuropean Communities callsa"noresidue" level). Thelevelofprotection reflected
intheECmeasures is,therefore, significantly different from thelevelofprotection reflected inthe
Codex standards (a"noresidue" levelasopposed toanunlimited residue level). TheECmeasures
indispute, insofarastheyrelate tooestradiol-17 ,testosterone andprogesterone, are,therefore,
notbased onexisting international standards asspecified inArticle 3.1.
8.80 WethusfindthattheECmeasures indispute (except totheextent theyrelate tothehormone
MGA) result inadifferent levelofsanitary protection thanwould beachieved bymeasures based on
therelevant Codex standards andare,therefore, notbased onexisting international standards asspecified
inArticle 3.1.
8.81 Wenextexamine whether theECmeasures withrespect tofiveofthesixhormones indispute,
which arenotbased onexisting international standards, otherwise areconsistent withtherequirements
oftheSPSAgreement (sections 4and5).Wethenaddress theECmeasures which relate tothesixth
hormone, MGA, forwhich nointernational standard exists (section 6).
4. Article 3.3: sanitary measures notbased oninternational standards
8.82 ThefactthattheECmeasures foroestradiol-17 ,testosterone, progesterone, zeranol and
trenbolonearenotbasedonexistinginternationalstandardsdoesnotnecessarilymeanthatthosemeasures
areinconsistent withtherequirements oftheSPSAgreement. Article 3.3reads asfollows:
"Members mayintroduce ormaintain sanitary orphytosanitary measures which result
inahigher levelofsanitary protection thanwould beachieved bymeasures based on
therelevant international standards, guidelines orrecommendations, ifthere isa
scientific justification, orasaconsequence ofthelevel ofsanitary orphytosanitary
protection aMember determines tobeappropriate inaccordance withtherelevant
provisions ofparagraphs 1through 8ofArticle 5.Notwithstanding theabove, all
measures which result inalevelofsanitary orphytosanitary protection different from
thatwhich would beachieved bymeasures based oninternational standards, guidelines
386Seepara. 8.76.
387Seepara. 8.65.WT/DS48/R/CAN
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orrecommendations shall notbeinconsistent with anyother provision ofthis
Agreement".
Afootnote toArticle 3.3,firstsentence, thenspecifies:
"Forthepurposes ofparagraph 3ofArticle 3,there isascientific justification if,on
thebasis ofanexamination andevaluation ofavailable scientific information in
conformity withtherelevant provisions ofthisAgreement, aMember determines that
therelevant international standards, guidelines orrecommendations arenotsufficient
toachieve itsappropriate levelofsanitary orphytosanitary protection".
Theconcept ofan"appropriate levelofsanitary protection" isdefined inparagraph 5ofAnnex Aof
theSPSAgreement as:
"The levelofprotection deemed appropriate bytheMember establishing asanitary
...measure toprotect human, animal orplant lifeorhealth within itsterritory".
ANote tothisparagraph addsthefollowing:
"Many Members otherwise refertothisconcept asthe'acceptable levelofrisk'".
(a) Requirements forjustification
8.83 Forasanitary measure tobejustified under Article 3.3themeasure needs, firstofall,to"result
inahigher level ofsanitary protection thanwould beachieved bymeasures based ontherelevant
internationalstandards,guidelinesorrecommendations".Werecallthecomparisonmadeabovebetween
thelevelofprotection reflected intheECmeasures andthatimplied intheCodex standards foreach
ofthehormones atissue, inparticular thatthelevel reflected intheECmeasures isdifferent from
thatimplied intheCodex standards.388Forpurposes ofouranalysis under Article 3.3,weassume
thattheformer levelishigher thanthelatter, inlinewiththefirstsentence ofArticle 3.3.Inaddition,
thesanitary measure needs tofulfil oneofthefollowing twoconditions:
- there isa"scientific justification" forimposing themeasure, i.e.,theMember imposing the
measure hasdetermined "onthebasisofanexamination andevaluation ofavailable scientific
information inconformity withtherelevant provisions of[theSPS] Agreement, ...thatthe
relevant international standards, guidelines orrecommendations arenotsufficient toachieve
itsappropriate levelofsanitary ...protection" ("the firstexception"); or
- themeasure is"aconsequence ofthelevelofsanitary ...protection aMember determines to
beappropriate inaccordance withtherelevant provisions ofparagraphs 1through 8ofArticle 5"
("the second exception").
However, according tothesecond sentence ofArticle 3.3,evenifoneofthese conditions isfulfilled,
theparty imposing themeasure must stillcomply withtheother provisions oftheSPSAgreement.
8.84 Wewillconsider firstwhether either thefirstorthesecond exception outlined above ismet.
Indoing so,wefirstaddress therelationship anddifference between these twoexceptions. Canada
argues thatthetwoexceptions aresimilar andcomplementary: thefirstexception dealswithsituations
where aninternational standard isoutdated insuchawaythatitdoesnotprovide thelevelofprotection
itwasthought tohaveprovided; thesecond exception deals withsituations where aninternational
388Seepara. 8.80.WT/DS48/R/CAN
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standard isvalid butwhere theMember 'slevelofprotection isdifferent fromthelevelofprotection
provided bytheinternational standard.389TheEuropean Communities argues thatthefirstexception
isfulfilled when theinternational standard isinadequate, faulty orobsolete from ascientific point of
view andthat,according tothesecond exception, aMember isinanycaseentitled tointroduce or
maintain measures which aimatachieving itsappropriate level ofprotection, tobedetermined in
accordance withArticle 5oftheSPSAgreement.390
8.85 Wenotethatbothexceptions explicitly refertoother provisions oftheSPSAgreement. The
firstexception contains thefollowing reference: "...onthebasis ofanexamination andevaluation
ofavailable scientific information inconformity withtherelevant provisions of[theSPS]Agreement ..."
(emphasis added). Thesecond exception refers to"...therelevant provisions ofparagraphs 1through 8
ofArticle 5"(emphasis added). Article 3.3,second sentence, inturn,explicitly states thatevenifthe
sanitary measure atissuefallsunder oneofthetwoexceptions ofArticle 3.3,firstsentence, thesanitary
measure inquestion stillneeds tobeconsistent withallprovisions oftheSPSAgreement other than
Article 3.
8.86 Wefind,therefore, that,whatever thedifference might bebetween thetwoexceptions, asanitary
measure canonlybejustified under Article 3.3ifitisconsistent withtherequirements contained in
Article 5.IfweweretofindthattheECmeasures indispute areinconsistent withtherequirements
imposed byArticle 5,these measures cannot bejustified under Article 3.3.However, evenifwefind
thattheECmeasures atissueareconsistent withtherequirements imposed byArticle 5,thiswillstill
notbesufficient forthese measures tobejustified under Article 3.3since toreach thatconclusion we
alsoneedtofindthattheECmeasures indispute fulfilallprovisions oftheSPSAgreement other than
Articles 3and5(incasuArticle 2).
(b) Burden ofproof
8.87 Werecall thefindings made above ontheburden ofproof under theSPSAgreement391,in
particular thatfortheobligations imposed bytheSPSAgreement thatarerelevant tothiscase, the
party contesting asanitary measure (incasuCanada) bears theinitial burden ofproof inthatithas
topresent aprima faciecaseofinconsistency withtheSPSAgreement, afterwhich theburden ofproof
shifts totheparty imposing themeasure (incasutheEuropean Communities).
8.88 Weconsider thatthisallocation ofburden totheparty imposing asanitary measure is,forthe
reasons setoutabove392,applicable toArticle 3.3andparticularly justified under thefirstsentence
thereof which contains specific requirements tobefulfilled foraMember tojustify asanitary measure
which isnotbased onaninternational standard.
8.89 Onepurpose oftheSPSAgreement, asexplicitly recognized inthepreamble, istopromote
theuseofinternational standards, guidelines andrecommendations. Tothatend,Article 3.1imposes
anobligation onallMembers tobasetheirsanitary measures oninternational standards except as
otherwise provided forintheSPSAgreement, andinparticular inArticle 3.3thereof. Inthissense,
Article 3.3provides anexception tothegeneral obligation contained inArticle 3.1. Article 3.2,in
turn,specifies thatthecomplaining party hastheburden ofovercoming apresumption ofconsistency
withtheSPSAgreement inthecaseofameasure based oninternational standards. Itthereby suggests
389Seepara. 4.78.
390Seeparas. 4.86-4.89.
391Seeparas. 8.51-8.58.
392Seeparas. 8.54-8.57.WT/DS48/R/CAN
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byimplication thatwhen ameasure isnotsobased, theburden isontherespondent toshow thatthe
measure isjustified under theexceptions provided forinArticle 3.3.
8.90 Wefind,therefore, thatoncethecomplaining party provides aprima faciecase(i)thatthere
isaninternational standard withrespect tothemeasure indispute, and(ii)thatthemeasure indispute
isnotbased onthisstandard, theburden ofproof under Article 3.3shifts tothedefending party.393
8.91 Since inthisdispute wehavealready found thatthere existinternational standards394andthat
theECmeasures atissue arenotbased onthese standards395,wefindthattheburden ofjustifying the
measures indispute under Article 3.3,andinparticular under thefirstsentence thereof, restsonthe
European Communities.
8.92 Insummary ,insections 3and4wehavefound that: (i)there existinternational standards,
asdefined inArticle 3.1andparagraph 3(a)ofAnnex AoftheSPSAgreement, withrespect tothe
ECmeasures indispute totheextent theyrelate tofiveofthesixhormones atissue (allbutMGA);
(ii)theECmeasures indispute, inasfarastheyrelate tothese fivehormones, arenotbased onthese
international standards, asrequired inArticle 3.1;and(iii)theECmeasures, totheextent theyare
notbased onthese international standards, canonlybejustified under Article 3.3ifthese measures
meet, interalia,therequirements imposed byArticle 5.
8.93 Inthenextsection wewill,therefore, examine whether theECmeasures indispute withrespect
tothefivehormones atissueforwhich international standards existareconsistent withtherequirements
imposed byArticle 5.
5. Article 5:"Assessment ofRisk andDetermination oftheAppropriate Level of
Sanitary orPhytosanitary Protection"
(a) Riskassessment andriskmanagement
8.94 Article5oftheSPSAgreementdealsmainly396withtwoseparateaspectsofaMember'sdecision
toenact ormaintain asanitary measure. These twoaspects areseparated intheSPSAgreement, which
provides forspecific rights andobligations inrespect ofeachofthem.
8.95 Thefirstaspect relates totheexercise ofassessing therisks tohuman, animal orplant life
orhealth against which asanitary measure isintended toprotect. This isreferred tointhe
393Thisapproach isinlinewithestablished practice under GATT 1947 andGATT 1994 where, forexample, theburden
ofproof tojustify aninconsistency withanother GATT provision under Article XXalsorestsonthedefending party. See
PanelReporton"Canada-AdministrationoftheForeignInvestmentReviewAct",adoptedon7February1984,BISD30S/140,
p.164, para. 5.20; on"United States -Section 337oftheTariff Actof1930", adopted on7November 1989, BISD 36S/345,
p.393, para.5.27 andon"United States -Standards forReformulated andConventional Gasoline", op.cit.,p.38, para. 6.20.
Inthisrespect, wealsonotethattheReport oftheAppellate Body on"United States -Measures Affecting Imports ofWoven
Wool Shirts andBlouses from India" stated thefollowing withrespect totheburden ofproof under Articles XXandXI:2(c)(i)
ofGATT: "Articles XXandXI:(2)(c)(i) arelimited exceptions from obligations under certain other provisions oftheGATT
1994, notpositive rules establishing obligations inthemselves. They areinthenature ofaffirmative defences. Itisonly
reasonable thattheburden ofestablishing such adefence should restontheparty asserting it"(op.cit.,p.16).
394Seepara. 8.73.
395Seepara. 8.80.
396Except forArticle 5.8which hasnotbeen invoked inthisdispute.WT/DS48/R/CAN
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SPSAgreement asriskassessment .397With respect tofoodsafety, thepotential adverse effects (if
any)related toaspecific substance areestablished together withtheprobability ofoccurrence ofany
sucheffects.398
8.96 According toArticle 5.1,aMember needs toensure thatitssanitary measures arebased on
anassessment ofrisks. Theobligation tobaseasanitary measure onariskassessment maybeviewed
asaspecific application ofthebasic obligations contained inArticle 2.2oftheSPSAgreement which
provides that"Members shallensure thatanysanitary ...measure isapplied onlytotheextent necessary
toprotect human, animal orplantlifeorhealth, isbased onscientific principles andisnotmaintained
without sufficient scientific evidence ..."(emphasis added). Articles 5.1to5.3sumupfactors aMember
needs totakeintoaccount inmaking thisassessment ofrisks.399
8.97 Aswillbeoutlined below400,anassessment ofrisksis,atleastforriskstohuman lifeorhealth,
ascientific examination ofdataandfactual studies; itisnotapolicy exercise involving social value
judgments made bypolitical bodies.
8.98 Thesecond aspect ofaMember 'sdecision toenact ormaintain asanitary measure relates,
interalia,tothedetermination andapplication oftheappropriate levelofsanitary protection bythat
Member against theriskstohuman, animal orplantlifeorhealth which havebeenassessed inaccordance
withArticles 5.1to5.3.Thisaspect iscommonly referred tobytheparties tothisdispute asanessential
partofriskmanagement .401TheMember wishing toimpose asanitary measure mustdecide theextent
towhich itcanaccept thepotential adverse effects related toaspecific substance which havebeen
identified intheriskassessment.
8.99 Articles 5.4to5.6areparticularly relevant totheriskmanagement decision. Article 5.4
establishes theobjective ofminimizing negative trade effects inthedetermination byaMember of
itsappropriate levelofprotection. Article 5.5aimsatachieving consistency intheapplication ofthe
concept ofappropriate level ofprotection. Article 5.6,inturn, provides thatthesanitary measure
which isfinally adopted shallnotbemore trade-restrictive thanrequired toachieve theappropriate
levelofprotection oftheMember concerned. Articles 5.4to5.6maybeviewed asspecific applications
ofthebasic obligations provided forinArticle 2.2which, interalia,states that"Members shallensure
thatanysanitary orphytosanitary measure isapplied onlytotheextent necessary toprotect human,
animal orplant lifeorhealth" (emphasis added) andArticle 2.3which provides that"Members shall
ensure thattheirsanitary andphytosanitary measures donotarbitrarily orunjustifiably discriminate
between Members where identical orsimilar conditions prevail ..."andthat"Sanitary andphytosanitary
measures shallnotbeapplied inamanner which would constitute adisguised restriction oninternational
trade" (emphasis added).
397SeethetitleofArticle 5oftheSPSAgreement ("Assessment ofrisk...")andAnnex AoftheSPSAgreement providing
adefinition for"risk assessment".
398Seethedefinition of"risk assessment" contained inparagraph 4ofAnnex AoftheSPSAgreement, discussed below
inpara. 8.101.
399Article 5.7deals withcases where relevant scientific evidence isinsufficient atwhich point aMember may, under
certain conditions, takeprovisional sanitary measures. TheEuropean Communities hasexplicitly stated thatthisprovision
does notapply totheECmeasures indispute.
400Seeparas. 8.101 and8.107-8.110.
401Seeparas. 4.97, 4.106 and4.124.WT/DS48/R/CAN
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8.100 Aswillbeoutlined below402,theriskmanagement phase involves non-scientific considerations,
suchassocial value judgments.
(b) Articles 5.1to5.3: riskassessment
8.101 According toArticle 5.1:
"Members shallensure thattheirsanitary orphytosanitary measures arebased onan
assessment, asappropriate tothecircumstances, oftheriskstohuman, animal orplant
lifeorhealth, taking intoaccount riskassessment techniques developed bytherelevant
international organizations".
Paragraph 4ofAnnex AoftheSPSAgreement defines "riskassessment" withrespect tocontaminants
(including residues ofthehormones atissue) as
"theevaluation ofthepotential foradverse effects onhuman oranimal health arising
fromthepresence of...contaminants ...infood, beverages orfeedstuffs" (emphasis
added).
Guided bythewording ofthese provisions, weconsider that,inthisdispute, ariskassessment carried
outinaccordance withtheSPSAgreement should (i)identify theadverse effects onhuman health (if
any)arising from thepresence ofthehormones atissue when usedasgrowth promoters inmeator
meat products ,and(ii)ifanysuchadverse effects exist, evaluate thepotential orprobability of
occurrence ofthese effects.
8.102 Article5.1providesingeneralterms,withoutanylimitationintime,that"Membersshallensure
thattheir sanitary orphytosanitary measures arebased onanassessment, asappropriate tothe
circumstances, oftherisks...". Itdoesnotprevent thatwithrespect toasanitary measure enacted
before theentry intoforce oftheSPSAgreement, theriskassessment iscarried outorinvoked after
theentry intoforceofthatAgreement (andthusaftertheenactment ofthesanitary measure inquestion).
However, thefactthatasanitary measure maybeenacted before theentry intoforce oftheSPS
Agreement doesnotmean that,oncetheSPSAgreement entered intoforce, there isnoobligation for
theMember inquestion tobasethatmeasure onariskassessment.403Moreover, themore general
obligation contained inArticle 2.2oftheSPSAgreement explicitly provides that"Members shallensure
thatanysanitary orphytosanitary measure ...isbased onscientific principles andisnotmaintained
without sufficient scientific evidence ..."(emphasis added).
8.103 Wealsorecall ourfinding reached above onthespecific burden ofproof under Article 3.3404,
inparticular thattheburden ofproving thattherequirements imposed byArticle 3.3(inter alia,
consistency withArticle 5)aremet,restswiththeMember imposing asanitary measure which deviates
fromaninternational standard. Since theECmeasures examined inthissection (relating toallhormones
indispute other thanMGA) arenotbased onexisting international standards andneedtobejustified
under theexceptions provided forinArticle 3.3,theEuropean Communities hastheburden ofproving
thatitsmeasures arebased onariskassessment inaccordance withArticle 5.
402Seeparas. 8.163 ff.
403Ourreasoning andgeneral finding withrespect totheapplication ratione temporis oftheSPSAgreement developed
inparagraphs 8.27-8.30 alsoapplies toArticle 5.1ofthatAgreement.
404Seeparas. 8.87-8.91.WT/DS48/R/CAN
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8.104 Inthisrespect weconsider attheoutset thatitisfortheEuropean Communities tosubmit
evidence before thePanel thatitsmeasures arebased onariskassessment; itisnotforthePanel itself
toconduct itsownriskassessment onthebasisofscientific evidence gathered bythePanel orsubmitted
bytheparties during thePanel proceedings.
8.105 Wenextexamine: (i)thetechniques andfactors tobetaken intoaccount inariskassessment
inaccordance withArticle 5;(ii)whether theEuropean Communities hasdemonstrated theexistence
ofsuchariskassessment; and(iii)assuming thatsuchriskassessment exists, whether theEuropean
Communities hasdemonstrated thatitsmeasures atissue arebased onthisriskassessment.
(i) Techniques andfactors tobetaken intoaccount
8.106 None oftheparties suggest thatthereare"riskassessment techniques developed bytherelevant
international organizations" inthesense ofArticle 5.1which havetobetaken intoaccount inarisk
assessment forthehormones atissue.405Wenote, however, that,eventhough noformal decision has
asyetbeentaken byCodex withrespect toriskassessment techniques, Codex, andmore particularly
JECFA, hasalong-standing practice withrespect totheassessment ofrisksrelated toveterinary drug
residues (including hormone residues). Thetechniques thusdeveloped havebeenoutlined above.406
WealsonotetheReport oftheJointFAO/WHO Expert Consultation ontheApplication ofRiskAnalysis
toFood Standards Issues convened attherequest ofCodex inMarch 1995. InthisReport "risk
assessment" isdefined asfollows:
"The scientific evaluation ofknown orpotential adverse health effects resulting from
human exposure tofoodborne hazards. Theprocess consists ofthefollowing steps:
(i)hazard identification, (ii)hazard characterization, (iii)exposure assessment, and
(iv)riskcharacterization. Thedefinition includes quantitative riskassessment, which
emphasizes reliance onnumerical expressions ofrisk,andalsoqualitative expressions
ofrisk,aswellasanindication oftheattendant uncertainties" (p.6).407
8.107 Article 5.2provides forthefactors which aMember hastotakeintoaccount intheassessment
ofrisks:
"Intheassessment ofrisks, Members shall takeintoaccount available scientific
evidence; relevant processes andproduction methods; relevant inspection, sampling
andtesting methods; prevalence ofspecific diseases orpests; existence ofpest- or
disease-free areas; relevant ecological andenvironmental conditions; andquarantine
orother treatment".
8.108 None oftheparties involved inthisdispute hasargued thatanyfactors listed inArticle 5.2
other thanthefollowing three arerelevant foranassessment ofrisksrelated tothehormones atissue
inthiscase:
405Seeparas. 4.122-4.123.
406Seeparas. 8.62 ff.
407Arevised version ofthisdefinition hasbeenaccepted atthe12thsession oftheCodex Committee onGeneral Principles
heldinNovember 1996 andreads asfollows: "Ascientifically based process consisting ofthefollowing steps: (i)hazard
identification, (ii)hazard characterization; (iii)exposure assessment, and(iv)riskcharacterization" (Codex Alimentarius
Commission, CX/GP96/3).WT/DS48/R/CAN
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(i) available scientific evidence;
(ii) relevant processes andproduction methods;
(ii) relevant inspection, sampling andtesting methods.
Inparticular, wenotethatnone oftheparties hasargued thatfactors notlisted inArticle 5.2,such
asconsumer preferences, canbetaken intoaccount inariskassessment inaccordance withArticle 5.
8.109 Article 5.3sums uprelevant economic factors tobetaken intoaccount inassessing risksto
animal orplant lifeorhealth. Since thescope ofthisdispute islimited toissues ofhuman lifeor
health408,Article 5.3hasnoapplication tothematter under consideration.
8.110 Wefinally notethattheparties agree that,forthepurposes oftheECmeasures indispute,
ariskassessment inaccordance withArticle 5isascientific process aimed atestablishing thescientific
basis forthesanitary measure aMember intends totake.409
(ii) Theexistence ofariskassessment
8.111 TheEuropean Communities hasreferred tothefollowing scientific evidence concerning the
fivehormones atissue:410
- the1982Report oftheECScientific Veterinary Committee, Scientific Committee forAnimal
Nutrition andtheScientific Committee forFood onthebasis oftheReport oftheScientific
Group onAnabolic Agents inAnimal Production411("Lamming Report");
- the1983SymposiumonAnabolicsinAnimalProductionoftheOfficeinternationaldesepizooties
("OIE")412("1983 OIESymposium");
- the1987 Monographs oftheInternational Agency forResearch onCancer ("IARC") onthe
Evaluation ofCarcinogenic Risks toHumans, Supplement 7413("1987 IARC Monographs");
- the1988 and1989 JECFA Reports414;
- the1995 European Communities Scientific Conference onGrowth Promotion inMeat
Production415("1995 ECScientific Conference");
- articles andopinions byindividual scientists relevant totheuseofhormones (three articles
inthejournal Science, onearticle intheInternational Journal ofHealth Service, onereport
inThe Veterinary Record andseparate scientific opinions ofDr.H.Adlercreutz,
408Seepara. 8.22.
409Seeparas. 4.98 and4.124.
410Seepara. 4.125.
411Seepara. 2.28.
412Seepara. 4.17.
413Seeparas. 4.153-4.155.
414Seeparas. 2.22-2.25.
415Seepara. 2.33.WT/DS48/R/CAN
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Dr.E.Cavalieri, Dr.S.S.Epstein, Dr.J.G.Liehr, Dr.M.Metzler, Dr.Perez-Comas and
Dr.A.Pinter, allofwhom werepartoftheECdelegation atourjointmeeting withexperts).416
8.112 TheEuropean Communities alsoreferred toseveral reports oftheEuropean Parliament (the
Nielsen Report of1981, thefirstCollins Report of1985, thesecond Collins Report of1989 andthe
Pimenta Report of1989)417andopinions oftheECEconomic andSocial Committee (of1981 and
1984).418However, werecall thefindings wereached above, inparticular thatriskassessment isa
scientific process. Thus, weconsider thatthenon-scientific reports andopinions oftheEuropean
Parliament andtheECEconomic andSocial Committee, which evaluate thescientific andotherreports
submitted tothem, arenotpartoftheriskassessment process, butoftheriskmanagement process,
further elaborated below.419
8.113 Wenextconsider whether thescientific evidence andattendant evaluation referred tobythe
European Communities constitutes ariskassessment inthesense ofArticle 5.Werecall thatunder
theSPSAgreement ariskassessment should, forthepurposes ofthisdispute, identify theadverse
effects onhuman health arising fromthepresence ofthespecific hormones atissuewhen usedasgrowth
promoters inmeatormeatproducts and,ifanysuchadverse effects exist, evaluate thepotential or
probabilityofoccurrenceoftheseeffects.420Wefurtherrecallthatariskassessmentshouldbeascientific
examination ofdataandstudies421andthattheSPSAgreement setsoutfactors which needtobetaken
intoaccount inariskassessment.422Wefinally recall thatnoriskassessment techniques, asreferred
toinArticle 5.1,haveasyetbeenformally adopted byCodex.423TheAgreement doesnotfurther
specify therequirements ofwhatconstitutes ariskassessment inaccordance withArticle 5.
8.114 WenotethattheEuropean Communities hasinvoked several scientific reports which appear
tomeetthese minimum requirements ofariskassessment (inparticular theLamming Report andthe
1988 and1989 JECFA Reports) andthatthescientists advising thePanel seemed toconsider these
reports, fromascientific andtechnical point ofview, toberiskassessments.424Weshall, therefore,
forthepurposes ofthisdispute, assume thattheEuropean Communities hasmetitsburden of
demonstrating theexistence ofariskassessment carried outinaccordance withArticle 5.
416With respect tothescientific evidence referred tobytheEuropean Communities inrelation tothepotential adverse
effects ofthehormones atissue onthehealth orlifeofliveanimals ,werecall ourfindings reached inparagraph 8.22that
theanimal health arguments invoked bytheEuropean Communities exclusively relate totheECimport banofliveanimals
(which doesnotfallwithin thescope oftheECmeasures indispute) andthatthese arguments need, therefore, nottobe
taken intoaccount within thescope ofthisdispute.
417Seeparas. 2.31 and4.19.
418Seepara. 4.18.
419Seeparas. 8.163 ff.
420Seepara. 8.101.
421Seepara. 8.110.
422Seeparas. 8.107 and8.108.
423Seepara. 8.106.
424See,ingeneral, answers byexperts toPanel Questions 5and13,paras. 6.50ff.and6.141-6.146 and,inparticular,
Dr.Arnold atpara. 6.56, Dr.McLean atpara. 6.144 andopinion ofDr.Ritter, Transcripts ofthejointmeeting withexperts
of17February 1997, paras. 20and352.WT/DS48/R/CAN
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(iii) Sanitary measures tobebased onariskassessment
8.115 Article 5.1requires Members to"ensure thattheirsanitary ...measures ...arebased onan
assessment ...oftheriskstohuman ...lifeorhealth". Itdoesnot,however, specify howtodetermine
whether ameasure isbased onariskassessment. Inourview, thisdetermination hasbothaprocedural
andasubstantive aspect.
Procedural requirements
8.116 Notwithstanding thefactthatArticle 5doesnotcontain specific procedural requirements for
aMember tobaseitssanitary measures onariskassessment, weconsider that,according totheordinary
meaning ofthewords based onputintheircontext andinlightoftheobject andpurpose ofArticle 5425,
thereisaminimum procedural requirement contained inArticle 5.1.Inourview, theMember imposing
asanitary measure needs tosubmit evidence thatatleastitactually tookintoaccount ariskassessment
when itenacted ormaintained itssanitary measure inorder forthatmeasure tobeconsidered asbased
onariskassessment.
8.117 Wenotethatinthisdispute theEuropean Communities, which hastheburden ofproving that
itbased itsmeasures onariskassessment, hasnotprovided anyevidence thatthestudies itreferred
to(insofarastheycanbeconsidered aspartofariskassessment) orthescientific conclusions reached
therein, haveactually beentaken intoaccount bythecompetent ECinstitutions either when itenacted
these measures (in1981 and1988) oratanylaterpoint intime. Wenote, inthisrespect, thatnone
ofthepreambles totheECmeasures atissue mention anyofthescientific studies referred tobythe
European Communities. These preambles onlyrefertothenon-scientific reports andopinions ofthe
European Parliament andtheECEconomic andSocial Committee, which cannot beconsidered aspart
ofariskassessment.426
8.118 Inparticular withrespect tothearticles andopinions ofindividual scientists onwhich the
European Communities focused ourattention, wenotethattheEuropean Communities hasargued that
some ofthese articles andopinions (inparticular those published in1995and1996) arewhatitcalled
"new evidence" ofwhich itwasonlyinformed during thePanel process.427Insofarasthatisthe
case, these articles andopinions cannot forthepurposes ofthisdispute beconsidered aspartofarisk
assessmentonwhichtheEuropeanCommunitiesbaseditsmeasuresunlesstherewouldbesomeevidence
thatthecompetent ECinstitutions actually considered these articles andopinions orreexamined the
potential risksrelated tothespecific substances atissueinlightofthese articles andopinions. Inthat
event, theEuropean Communities would thenhaveconfirmed orchanged itsearlier conclusions on
thebasis ofsuchconsideration orreexamination. According totheterms ofreference given tousas
adispute settlement panel, wehavenomandate toreexamine theriskassessment referred tobythe
European Communities inlightofthis"new evidence", nortomake ourownriskassessment. These
articles andopinions, insofarastheyconstitute "new evidence" gathered bytheEuropean Communities
during thePanel process can,therefore, from aprocedural point ofview, notbeconsidered aspart
ofariskassessment onwhich theEuropean Communities based itsmeasures indispute.428
425Inaccordance withtherules oftreaty interpretation contained inArticle 31oftheVienna Convention.
426Seepara. 8.112.
427Seeparas. 4.160-4.169. However, lateroninthePanel process, theEuropean Communities confirmed thatmany
ofthese articles andopinions constitute evidence which wasalready taken intoaccount intheother studies referred toby
theEuropean Communities. Insofarasthisiscorrect, seeparas. 8.135 ff.
428These articles andopinions are,from asubstantive point ofview, further addressed inparas. 8.133 ff.WT/DS48/R/CAN
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8.119 Forthese reasons, wefindthattheEuropean Communities hasnotmetitsburden ofproving
thatitmettheminimal procedural requirement contained inArticle 5.1andthat,therefore, theEC
measures indispute areinconsistent withtherequirements ofArticle 5.1.
Substantive requirements
8.120 EveniftheEuropeanCommunitieswouldhavefulfilledtheseminimumproceduralrequirements,
there would stillbeaneedtoexamine thesubstantive requirements contained inArticle 5.1From
asubstantive point ofview, weconsider thatinthisdispute weshould, inaccordance withtheordinary
meaning ofthewords based onputintheircontext andinlightoftheobject andpurpose ofArticle
5429,proceed asfollows todetermine whether theECmeasures atissuearebased onariskassessment:
(i)weneedtoidentify thescientific conclusions reached ineachofthestudies referred tobytheEuropean
Communities; (ii)weneedtoidentify thescientific conclusion reflected intheECmeasures indispute;
and(iii)weneedtodetermine whether thescientific conclusion reflected intheECmeasures canbe
considered asbeing inconformity withanyofthose reached inthestudies referred tobytheEuropean
Communities.
8.121 Forpurposes ofthisanalysis, wefirstaddress thestudies referred tobytheEuropean
Communities which specifically address oneormore ofthehormones indispute when usedforgrowth
promotion purposes before examining thestudies which generally relate tooneormore ofthese
hormones.
1. Scientific conclusions reached inthestudies referred tobytheEuropean Communities
which specifically address oneormoreofthehormones indispute when usedforgrowth
promotion purposes
8.122 TheLamming Report cametothefollowing conclusions withrespect tothepotential foradverse
effects onhuman health arising from thepresence inmeat ofresidues ofthehormones indispute
administered forgrowth promotion purposes:
"5.1. TheScientific Working Group isoftheopinion thattheuseofoestradiol-17 ,
testosterone andprogesterone [thethree natural hormones indispute] andthose
derivatives which readily yield theparent compound onhydrolysis afterabsorption
fromthesiteofapplication, would notpresent anyharmful effects tothehealth ofthe
consumer when usedunder theappropriate conditions asgrowth promoters infarm
animals .
5.2. Evaluation ofthedataon'trenbolone 'and'zeranol '[twoofthethreesynthetic
hormones indispute] revealed thatsome dataonthehormonal no-effect-level andthe
toxicology ofthese compounds andtheirmetabolites arestillmissing.
5.3. TheScientificWorkingGroupconsidersitnecessarythatadditionalinformation
beprovided before afinalconclusion canbegiven ontrenbolone andzeranol" (emphasis
added).430
TheScientific Working Group continued itsreview oftrenbolone andzeranol upto1985 butwas
dismantled bytheECCommission justbefore itwastosubmit itsfinalreport.
429Inaccordance withtherules oftreaty interpretation contained inArticle 31oftheVienna Convention.
430Seepara. 2.28.WT/DS48/R/CAN
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8.123 Some ofthemembers ofthegroup published, intheirpersonal capacity, theunofficial report
in"TheVeterinary Record". Theconclusions reached withrespect tothepotential foradverse effects
onhuman health arising fromthepresence inmeatofresidues oftrenbolone andzeranol administered
forgrowth promotion purposes, were thefollowing:
"(1) Wehaveexamined theextensive dataavailable concerning thetoxicology of
trenbolone andzeranol.
(2) Webelieve thereisadequate evidence frombothshorttermandlongtermtests
thatthese compounds andtheirmetabolites found asresidues donotshow
significant genotoxic potential.
...
(5) Thelevels oftrenbolone andzeranol andtheirmajor metabolites found inedible
tissue, following accepted husbandry practices, aresubstantially below the
hormonally effective doses inanimal testsystems andtherefore donotpresent
aharmful effect tohealth "(emphasis added).431
8.124 Withrespect tothe1983OIESymposium ,wenotethatthereport ofthesymposium consists
ofabookwithaseries ofarticles byindividual scientists orgroups ofscientists. Noformal scientific
conclusion wasagreed byallparticipants orbytheOIEitself. Thebookcontains, however, aforeword
tothearticles which includes thefollowing statement withrespect tothepotential foradverse effects
onhuman health arising fromthepresence inmeatofresidues ofthethreenatural hormones indispute
administered forgrowth promotion purposes:
"The myth thatallanabolics aredangerous tohuman health isstillverymuch alive
inmany countries. Itmustbediscredited. There iscommon agreement withtheproof
presented atthismeeting thattheendogenous anabolics (natural hormones) suchas
17-estradiol,progesterone,andtestosterone,whenadministeredasimplantsinanimals,
arenothazardous toman"(emphasis added).
TheEuropean Communities invokes twospecific quotes fromindividual articles submitted attheOIE
Symposium insupport ofitsmeasures.432However, these quotes, which onlystress theinherent
uncertainties ofscientific evidence andtheevolving character ofscience, donotseem toinvalidate
the"common agreement" outlined intheforeword quoted above.
8.125 The1988 JECFA Report came tothefollowing conclusion withrespect tothepotential for
adverse effects onhuman health arising from thepresence inmeat ofresidues ofallthree natural
hormones indispute administered forgrowth promotion purposes:
"The Committee therefore concluded thattheamount ofexogenous [oestradiol-17 ,
testosteroneandprogesterone]ingestedinmeatfromtreatedanimalswouldbeincapable
ofexerting ahormonal effect, andtherefore anytoxiceffect, inhuman subjects .
TheCommittee considered anADIunnecessary forahormone thatisproduced
endogenously inhuman beings andshows great variation inlevels according toage
andsex.TheCommittee concluded thatresidues arising fromtheuseof[anyofthe
three natural hormones indispute] asagrowth promoter inaccordance withgood
animal husbandry practice areunlikely toposeahazard tohuman health ...
431Seepara. 4.12.
432Seeparas. 4.157, 4.159.WT/DS48/R/CAN
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Onthebasisofitssafety assessment ofresidues of[anyofthethree natural hormones
indispute], andinviewofthedifficulty ofdetermining thelevels ofthishormone as
agrowth promoter incattle, theCommittee concluded thatitwasunnecessary to
establish anAcceptable Residue Level" (emphasis added).433
Asoutlined above434,the1988and1989JECFA Reports setADIs andMRLs forzeranol andtrenbolone
(twoofthethreesynthetic hormones indispute). JECFA reached theconclusion thattheirtoxiceffects
arelinked totheirhormonal effects andthat,therefore, ano-hormonal-effect levelcould beestablished
which would ensure thatresidues uptosuchlevelaresafe. JECFA alsoconcluded thatthesafety level
orADIitthusadopted would notbeexceeded atanytimeafterproper implantation (irrespective of
thewithdrawal period respected).
8.126 TheSteering Committee ofthe1995ECScientific Conference cametothefollowing conclusions
withrespect tothepotential foradverse effects onhuman health arising from thepresence inmeat
ofresidues ofthehormones indispute administered forgrowth promotion purposes:
"When usedasgrowth promoters, thenaturally occurring gonadal steroid hormones
(oestrogen, testosterone andprogesterone) canincrease thegrowth rate,theproportion
ofleanmeattofatandthefood-conversion efficiency ofsome species ofanimals ...
while theresidues ofhormone intheresulting meatarewithin thenormal physiological
range ...Totheextent thatimproved food-conversion efficiency reduces excretion
ofnitrogen andphosphorus perunitofmeatproduction, theenvironmental benefits
(while small) arelikely tobepositive. Thatisthebasis onwhich theSteering Group
endorses theconclusions ofWorking Group IIthattheconditions defined incountries
where theuseofthese hormones asgrowth promoters ispermitted areareasonable
safeguard ofpublic health .
Several materials similar intheirphysiological effects tothenatural sexhormones (such
astrenbolone andzeranol) arealsousedasgrowth promoters inmeatproduction ...
TheSteering Committee endorses theopinion ofWorking Group IIthatthedefinition
oftheMRL fortrenbolone anditsmetabolites reached byvarious international
committees [inter alia, JECFA] provide reasonable protection ofpublic health "
(emphasis added).435
Therelevant conclusions ofWorking Group IIoftheConference on"Assessment ofHealth Risk",
which specifically address thesafety ofthehormones atissue when usedasgrowth promoters, read
asfollows:
"Natural sexhormones
Atpresent, there isnoevidence forpossible health riskstotheconsumer duetothe
useofnatural sexhormones forgrowth promotion, since:
- Residue levels ofthese substances measured inmeat oftreated animals fall
within thephysiological range observed inmeat ofcomparable untreated
animals.
433Seepara. 2.22.
434Seeparas. 8.66-8.68.
435Seepara. 2.33.WT/DS48/R/CAN
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- Thedaily production ofsexhormones byhumans ismuch higher thanthe
amounts possibly consumed from meat, eveninthemost sensitive humans
(prepubertal children andmenopausal women).
- Duetoanextensive first-pass metabolism, thebioactivity ofingested hormones
islow,thusproviding afurther safety margin.
Zeranol andtrenbolone
...
Atthedoses needed forgrowth promotion, residue levels arewellbelow thelevels
regarded assafe(theMRLs). There are,atpresent, noindications ofapossible human
health riskfromthelowlevels ofcovalently-bound residues oftrenbolone "(emphasis
added).436
8.127 Ascanbededuced fromallconclusions outlined above, noneofthescientific evidence referred
tobytheEuropean Communities which specifically addresses thesafety ofsome orallofthehormones
indispute when usedforgrowth promotion, indicates thatanidentifiable riskarises forhuman health
from suchuseofthese hormones ifgood practice isfollowed. Allofthescientific studies outlined
above came totheconclusion thattheuseofthehormones atissue(allbutMGA, forwhich noevidence
wassubmitted) forgrowth promotion purposes issafe;mostofthesestudies adding thatthisconclusion
assumes thatgood practice isfollowed. Wenotethatthisconclusion hasalsobeenconfirmed bythe
scientific experts advising thePanel.437
2. Scientific conclusions reached inthestudies referred tobytheEuropean Communities
which generally relate tooneormore ofthehormones indispute
8.128 TheEuropean Communities putsparticular emphasis onthe1987IARC Monographs andthe
articles andopinions ofindividual scientists outlined above.438
8.129 The1987IARC Monographs ,insofarastheyrelate tohuman health439,contain evidence with
respect tothreegeneral categories ofhormones, namely oestrogens, androgens andprogestins, without
distinguishing thespecific hormones falling within eachofthese categories orthenatural hormones
436Ibid.
437Seeanswers byexperts toPanel Question 7,paras. 6.92ff,including theanswers byDr.André (atpara. 6.92) and,
albeitslightlyqualified,Dr.Lucier(atpara.6.94:"Dr.Lucierrespondedthat,tohisknowledge,therewasnopieceofscientific
evidence toindicate thatanyofthesixhormones inquestion hadunequivocally caused adverse effects inhumans when
administered andusedproperly. However, there wassome information available which raised concern foraslight effect
ontheincidence ofhuman disease"). Inthisrespect, wenoteDr.Lucier 'sstatement that,according tohistentative estimates,
between zeroandoneperson inamillion whoeat500grams ofmeat, treated withoestrogens forgrowth promotion purposes
inaccordance withgood practice, perdayovertheirlifetimes, getcancer (seeTranscripts ofthejointmeeting withexperts
of18February 1997, paras.742 and819). This0-1inamillion riskiscaused bythetotalamount ofoestrogens intreated
meat(theamount ofendogenous oestrogens being highly variable and,according toDr.Lucier, already being carcinogenic),
notbythesmall fraction thereof which isadded forgrowth promotion purposes andwhich isrelevant forthepurposes of
thisdispute. Moreover, thisestimate onlyrepresents astatistical range of0to1inamillion, notascientifically identified
risk. Theconcept of"zero risk", towhich thisstatement isclosely related, isfurther dealt withinparas. 8.152 ff.We
note, finally, thatallexperts confirmed thatthere isnoevidence thatparticular ormore significant health problems exist
incountries where thehormones atissue areallowed foradministration asgrowth promoters ascompared tocountries where
such useisprohibited (seeanswers byexperts toPanel Question 9,paras. 6.117-6.121).
438Seeparas. 4.151-4.174.
439Inthisrespect, werecall ourfinding thatwithin thescope ofthisdispute weneednottotakeintoaccount thearguments
made bytheEuropean Communities which relate toanimal health (seepara. 8.22).WT/DS48/R/CAN
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fromthesynthetic hormones.440TheMonographs classify oestrogens asagents which arecarcinogenic
(meaning thatthere issufficient evidence ofcarcinogenicity inhumans); androgens asagents which
areprobably carcinogenic; andprogestins asagents which arepossibly carcinogenic.441
8.130 Wenotethatthescientific evidence included inthese Monographs relates tothecarcinogenic
potential ofentire categories ofhormones orthehormones atissue ingeneral .TheMonographs do
notconsider thecarcinogenic potential ofthesehormones when usedspecifically forgrowth promotion
purposes orwithrespect toresidue levels comparable tothose present aftersuchuse.442Moreover,
theMonographs donotspecifically evaluate, asisrequired onthebasis ofparagraph 4ofAnnex A
oftheSPSAgreement443,thepotential foradverse effects arising from thepresence infood(incasu
meatormeatproducts) ofresidues ofthehormones indispute orfrom residue levels comparable to
those present infood.
8.131 Wefurther notethat,according tothescientific experts advising thePanel444,thedataandstudies
contained inthese Monographs withrespect tothecarcinogenic potential ofthehormones indispute
havebeenfullytaken intoaccount inthe1988 and1989JECFA Reports which, atseveral occasions,
explicitly refer tothese Monographs. Nowhere dothe1988 and1989 JECFA Reports reject the
conclusions reached inthe1987IARC Monographs. Onthecontrary, theMonographs constitute part
oftheevidence onwhich theJECFA Reports arebased. JECFA recognized thatallfivehormones
atissuehaveacarcinogenic potential butconcluded thatthispotential waslinked tothehormonal effect
ofthesehormones.445Since JECFA considered thattheadditional residues ofthethreenatural hormones
present intreated meatarenotcapable ofexerting anytoxic effect, itdecided thatitwasunnecessary
tosetADIs orMRLs forthesehormones.446Withrespect tozeranol andtrenbolone, JECFA identified
ano-hormonal-effect level andadopted, onthatbasis, ADIs andMRLs which, ifrespected, would
ensure thesafeuseofthesehormones.447TheIARC Monographs andJECFA Reports didnot,therefore,
reach contradictory butrather complementary scientific conclusions.
8.132 Forthese reasons, weconsider thatthe1987 IARC Monographs, insofarastheycanbe
regarded aspartofariskassessment forthespecific hormones atissuewhen usedasgrowth promoters
inthesense ofArticle 5.1,havebeentaken intoaccount in,anddonotcontradict, theother studies
referred tobytheEuropean Communities (inparticular the1988 and1989 JECFA Reports) which
440Asoutlined inpara.2.8, oestradiol-17 andzeranol areoestrogens; testosterone andtrenbolone areandrogens and
progesterone isaprogestin.
441Seepara. 4.155.
442Seepara. 4.154. Seealsoanswer byDr.Arnold toPanel Question 6,paras. 6.82 ff.
443Seepara. 8.101.
444Seeanswers byexperts toPanel Question 5(paras. 6.50ff.)where allexperts confirm thattheJECFA Reports took
intoaccount cancer risks. See,inparticular, statements made byDr.Randell, theCodex expert, atthejointmeeting with
experts of17February 1997 (Transcripts, paras. 239,297and436)andbyDr.McLean atthejointmeeting withexperts
of18February 1997 (Transcripts, para. 823).
445ThelinkmadebyJECFAbetweenhormonalandtoxiceffectdoesnotcontradicttheconclusionsintheIARCMonographs;
onthecontrary, since thelatter statethefollowing: "There isabasic incongruity between thehuman dataandtheanimal
carcinogenicity data. Asnoted earlier, however, theeffects ofthese chemicals [inter alia,thegeneral categories towhich
thehormones indispute belong] inhumans appear, atleastinmostcases, tobelinked tothehormonal milieu "(emphasis
added; seepara. 4.154).
446Seepara. 8.65.
447Seeparas. 8.66-8.68.WT/DS48/R/CAN
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explicitly conclude thatthespecific useofthese hormones asgrowth promoters inaccordance with
good practice issafe.
8.133 TheEuropean Communities finally invokes several articles andopinions ofindividual scientists .
These articles andopinions dealwiththecarcinogenic orgenotoxic potential ofhormones andcriticize
thescientific methodology orconclusions oftheotherstudies referred tobytheEuropean Communities.
Asummary ofthecontent ofsome ofthesearticles andopinions iscontained inparagraphs 4.154-4.166.
Thescientific evidence included inthese articles andopinions relates tothecarcinogenic orgenotoxic
potential ofentire categories ofhormones orthehormones atissueingeneral ;notwhen usedspecifically
forgrowth promotion purposes orwithrespect toresidue levels comparable tothose present aftersuch
use.448Moreover, these articles andopinions donotspecifically evaluate, asisrequired onthebasis
ofparagraph 4ofAnnex AoftheSPSAgreement, thepotential foradverse effects arising from the
presence infood(incasumeatormeatproducts) ofresidues ofthehormones indispute orfromresidue
levels comparable tothose present infood.
8.134 Ofthearticles andopinions invoked, theEuropean Communities hasputmuch emphasis on
theopinion ofDr.Liehr, ascientist withtheECdelegation, on"Potential Genotoxicity ofHormones".
Wenotethestatement byDr.Liehr himself thattheevidence hesubmitted isonlybased ontestscarried
outatelevated doses ofoestrogens andthattherelevance ofthese highdoseeffects topotential risks
related tothelowlevels ofoestrogens inmeat from growth promoted animals hasnotyetbeen
evaluated.449Moreover, werecall thatthisopinion onlyapplies tooneofthehormones indispute,
namely, oestradiol-17 anddoesnotaddress theuseofthishormone asagrowth promoter.
8.135 Wefurther notethat,according totheCodex expert advising thePanel, mostoftheevidence
contained inthesearticles andopinions andthepotential risksaddressed therein werealready evaluated
andtaken intoaccount inthe1988 and1989 JECFA Reports.450Indeed, intheevent these articles
andopinions should beconsidered asevidence which was,astheEuropean Communities itselfargued
attheendofthePanel proceedings, not"new" butwasalready taken intoaccount inthe1988or1989
JECFA Reports, theLamming Report orthe1995ECScientific Conference, thesearticles andopinions
would thennotinvalidate orcontradict thescientific conclusions reached inthese other studies, which
specifically address theuseofthehormones indispute forgrowth promotion purposes, butrather
constitute partoftheevidence onwhich these studies arebased.
8.136 Wealsonotethat,evenifthesearticles andopinions could beconsidered asscientific evidence
which ispartofariskassessment forthespecific hormones atissue when usedasgrowth promoters
inthesense ofArticle 5.1andwhich wasnotyetconsidered intheotherstudies invoked bytheEuropean
Communities, thescientific experts advising thePanel wereoftheviewthatthisevidence, asitstands
today,doesnotinvalidate orcontradict thescientific conclusions reached intheother studies invoked
bytheEuropean Communities which specifically relate tothesafety ofthehormones atissue when
usedforgrowth promotion purposes:
448Seepara. 2.22.
449Seepara. 4.160-4.161. Inthisrespect, wealsonotethefollowing statements byDr.Liehr: "...we havenogenotoxicity
dataatlowlevels" and"...Iagree ...thatatthemoment thisisaninteresting hypothesis andIhave never labelled itmore
thanahypothesis andIalsoagree ...thatmany pieces aremissing ..."(Transcripts ofthejointmeeting withexperts of
17February 1997, para. 330). ThefactthatDr.Liehr repeatedly called foramore thorough scientific examination ofthe
risksrelated tooestrogens andformore data, reveals thatthestudies heprovided tousdonotyetcontain conclusive evidence
ofanidentifiable risk.
450Seepara. 6.162 andTranscripts ofthejointmeeting withexperts of17February 1997, para. 297. Seealsoanswers
byexperts toPanel Question 5,paras. 6.50 ff.WT/DS48/R/CAN
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Dr.McLean:
"Some ofthenewdatathathasbeensubmitted particularly relies upon invivoand
invitrocarcinogenicity testing andalsosome ofthemutagenicity testing butIdonot
believe thatitisanymore significant thanthesortofdatathatwasavailable atthe
timetheoriginal appraisal wasmade [inthe1988 and1989 JECFA Reports]".451
Dr.Arnold:
"...from mypoint ofview, thesignificant newevidence which hasbeenproduced
since thatCommittee [the32nd and34thmeetings ofJECFA] didnotinvalidate the
basicconclusions andtherefore Istillamfeeling verycomfortable withtheconclusions
although Iadmit thatalotofnewevidence hasbeen produced bythescientific
community".452
Dr.Ritter:
"The nature ofscientific interpretation isthatlegitimate bona fideknowledgeable
scientists mayreach different conclusions from thesame setofdata. ButIthink the
consensus opinion ofthatConference [the1995 ECScientific Conference] wasthat
theweight ofevidence usedthencontinues toprevail now, andthattheassessments
andconclusions drawn thenarestillconsistent withtheavailable information now".453
"Iagree thatthere isfurther work thatisindicated. Iagree thatstatements made by
scientists, suchasDr.Liehr, willcontinue tocontribute toourunderstanding, butI
alsoagree thatthetotality ofevidence, re-evaluated asrecently asDecember 1995[by
the1995 ECScientific Conference], suggests thatthewayinwhich these substances
areusedandtheresidues which theyproduce, donotconstitute arisktohuman
health".454
Dr.Lucier:
"There isagroup ofscientists [including Dr.Liehr, ascientist withtheECdelegation]
whoarelooking attheroleofoxidated damage andgenotoxicity ofoestrogens ...But
forthisnarrow purpose thatwearetalking about today, about theinfluence ofthis
onadditional riskfromoestrogens fromeating, consuming meatcontaining oestrogens
from growth promoted animals, itdoesn 'thavetoomuch consequence. ...Iwould
come upwiththesame answer either case; there would benodifference intherisk.
SoIthink inthatrespect whether ornotoestrogen isgenotoxic, haslessconsequence
thenwhatwetalked about uptothispoint intime".455
451Transcripts ofthejointmeeting withexperts of17February 1997, para. 4.
452Ibid.,para. 356.
453Ibid.,para. 352.
454Ibid.,para. 424.
455Theother scientist advising thePanel, Dr.André didnotexplicitly express hisviews onthisissue butdidnotcontest
thestatements made bytheother scientists. Dr.McLean hasfurthermore answered intheaffirmative when asked whether
hebelieved thattheCodex standards arefullyadequate toaddress theproblem (Transcripts ofthejointmeeting withexperts
of17February 1997, para. 9).WT/DS48/R/CAN
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8.137 Forthesereasons,wefindthattheEuropeanCommunitieshasnotdemonstratedthatthescientific
evidence itreferred to,which generally addresses thesafety ofsome orallofthehormones indispute,
would indicate thatanidentifiable riskarises forhuman health from theuseofthese hormones for
growth promotion purposes ifgood practice isfollowed. Inthisrespect werecall thatallscientific
experts advising thePanel confirmed thisconclusion andstated that,asoftoday, noscientific evidence
isavailable which concludes thatanidentifiable riskarises from theuseofanyofthehormones at
issue forgrowth promotion purposes inaccordance withgood practice.456
8.138 Thefinding wethusmake does, ofcourse, notexclude thatfuture scientific developments could
require modifications tothescientific conclusions reached inthestudies referred tobytheEuropean
Communities.
3. Scientific conclusion reflected intheECmeasures
8.139 TheEuropean Communities banstheuseforgrowth promotion purposes ofanyofthehormones
indispute, including theuseofthese hormones inaccordance withgood practice. During thePanel
proceedings ithasmade clear thatitconsiders anyresidue levelofthese hormones tobeunsafe for
human health, setting itslevelofprotection ata"zero residue" level. Thescientific conclusion reflected
intheECmeasures indispute isthusthattheuseofthehormones indispute forgrowth promotion
purposes, eveninaccordance withgood practice457,poses anidentifiable risktohuman health.
4. Theconformity ofthescientific conclusion reflected intheECmeasures withthe
scientific conclusions reached inthestudies referred to
8.140 Inourview, thescientific conclusion reflected intheECmeasures indispute, i.e.,thatthe
useofthehormones indispute forgrowth promotion purposes, eveninaccordance withgoodpractice,
isnotsafe,doesnotconform toanyofthescientific conclusions reached intheevidence referred to
bytheEuropean Communities. Alltheevidence referred tobytheEuropean Communities which
specifically relates totheuseofthehormones atissue forgrowth promotion purposes concludes that
theuseofthesehormones asgrowth promoters inaccordance withgoodpractice issafe.458Moreover,
noneoftheevidence referred tobytheEuropean Communities which generally dealswithoneormore
ofthehormones indispute contradicts thisconclusion.459TheECimport banofmeatandmeatproducts
fromanimals treated withanyofthefivehormones atissueforgrowth promotion purposes, allegedly
necessary toprotect human health, insofarasitalsoapplies tomeatandmeatproducts fromanimals
treated withanyofthese hormones inaccordance withgood practice ,is,therefore, notbased onthe
scientific evidence submitted tothePanel.
8.141 TheEuropean Communities, however, submits thefollowing additional arguments (sections 5
and6).Wenotethatthese arguments havenotbeensupported byscientific evidence other thanthe
evidence examined above. Weconsider itnonetheless appropriate toexamine whether thesearguments
demonstrate thattheECmeasures indispute are,from asubstantive point ofview, based onarisk
assessment inaccordance withArticle 5.1.
456Seefootnote 437.
457Since, according totheexperts advising thePanel (answers byexperts toPanel Question 3,paras. 6.31ff.),anyuse
ofthehormones indispute willalways leave some residue level, albeit averysmall one,theadministration ofthese hormones
inaccordance withgood practice willalsoleave some residue andthusnotachieve theEC"zero residue" levelofprotection.
458Seepara. 8.127.
459Seepara. 8.137.WT/DS48/R/CAN
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5. General categories ofrisksinvoked bytheEuropean Communities
8.142 TheEuropean Communities argues thatithasbased itsbanontheexistence ofthefollowing
categories ofrisksrelated tothehormones atissue: (i)risksarising fromthenature andmode ofaction
ofthehormones; (ii)risksarising fromtheaction ofmetabolites; (iii)risksarising from theaction
ofcombinations (orcocktails) ofhormones andfrommultiple exposure ofhumans; (iv)risksarising
fromproblems related todetection andcontrol ofhormones; (v)risksarising fromtheadministration
anduseofhormones; and(vi)risksarising fromvarious other parameters, inparticular theinherent
limits toscience.460
8.143 Canada argues thattheEuropean Communities hasnever performed anappropriate assessment
ofthese alleged risksandhas,inanyevent, notrelied on,norputforward, anyassessment ofthese
risksthatcould serve asabasis fortheECban.461
8.144 Werecall thattheEuropean Communities hasnotreferred toanyscientific evidence, other
thanthatexamined above462,inwhich thecategories ofrisksputforward bytheEuropean Communities
havebeenassessed andthatnoneofthescientific evidence referred tobytheEuropean Communities
reached theconclusion thatanyofthehormones indispute when administered forgrowth promotion
purposes inaccordance withgood practice hasanadverse effect onhuman health.463
8.145 Moreover, withrespect tothealleged risks related tothenature andmode ofaction ofthe
hormones indispute (including carcinogenicity andlong-term effects) andtheaction ofmetabolites
orcombinations ofandmultiple exposure tothese hormones (i.e.,thefirstthree categories ofrisks
invoked bytheEuropean Communities), wenotethestatements ofthescientific experts advising the
Panel thattheavailable datarelating totheseriskshaveallbeentaken intoaccount bytheJECFA Reports
and/or theLamming Report and/or the1995ECScientific Conference.464Allthreereports concluded
thattheserisksdonotmaterialize ifthehormones indispute areusedasgrowth promoters inaccordance
withgoodpractice. TheEuropean Communities hasnotprovided anyevidence tothecontrary. The
ECimport banofmeatandmeatproducts fromanimals treated withanyofthefivehormones atissue
forgrowth promotion purposes, insofarasitalsoapplies tomeatandmeatproducts from animals
treated withanyofthese hormones inaccordance withgood practice ,is,therefore, notbased onan
assessment ofthese categories ofrisks.
8.146 Inaddition, withrespect tothealleged risksarising from problems related tothedetection,
control, administration anduseofthehormones indispute (i.e.,thefourth andfifthcategory ofrisks
invoked bytheEuropean Communities), wenotethattheEuropean Communities hasnotreferred to
evidence, other thanthatoutlined above465,inwhich anassessment ismade ofthepossible adverse
health effects related tothepotential abuse ofthesespecific hormones when usedforgrowth promotion
purposes. TheEuropean Communities hasrestricted itself topointing outthecondition contained in
many ofthescientific conclusions mentioned above, namely thatthesafety ofthehormones istoa
460Seepara. 4.150.
461Seepara. 4.122.
462Seeparas. 8.122 ff.
463Seepara. 8.140.
464Seeanswers byexperts toPanel Question 5,paras. 6.50ff.,inparticular theanswers byDr.Arnold, Dr.McLean
andDr.Ritter andtheopinions ofDr.Randell, para. 6.165 (seealsoTranscripts ofthejoint meeting withexperts of
17February 1997, paras. 239, 374and436andof18February 1997, paras. 730and823).
465Seeparas. 8.122 ff.WT/DS48/R/CAN
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certain extent conditional upontheiradministration inaccordance withgoodpractice466,without further
providing anassessment ofthepotential adverse effects related tononcompliance withsuchpractice.
8.147 Wefurther notethattheEuropean Communities argues thatifitweretoallow theuseofthe
threenatural hormones atissueitwould encounter special problems ininspecting, sampling ortesting
forresidues ofthesehormones inmeat. These problems relate, according totheEuropean Communities,
totheinherent characteristics ofthenatural hormones which make themindistinguishable fromnatural
hormones present endogenously inmeatorpresent inmeatsubsequent totherapeutic orzootechnical
useofthese hormones.467
8.148 Werecall that,inthisdispute, thefactors which canbetaken intoaccount inariskassessment
underArticles5.1and5.2arelimitedto"availablescientificevidence"and"relevantinspection,sampling
andtesting methods".468Totheextent thattheproblems ininspecting (sampling andtesting) natural
hormones would actually poseariskandcould thus, arguably, betaken intoaccount asariskarising
from"relevant inspection, sampling andtesting methods" inthesense ofArticle 5.1,weconsider that
theEuropean Communities encounters thesame problems ininspecting fornatural hormones under
itscurrent regime. TheECbanofnatural hormones usedforgrowth promotion purposes, combined
withitstolerance forthesehormones when usedfortherapeutic orzootechnical purposes orwhen present
endogenously inmeatandother foods, would seem tocause more problems ininspecting forbanned
natural hormones thanaregime where theuseofallnatural hormones would beallowed incombination
with, forexample, amaximum residue ortolerance levelforallnatural hormones inanymeatregardless
oftheorigin anduseofthese hormones. Indeed, onlyunder theECcurrent regime doestheproblem
ofhowtodistinguish between endogenous andadded natural hormones arise; under aregime with
anMRL ortolerance levelforallnatural hormones therewould benoneedtodistinguish endogenous
from added natural hormones.
8.149 With respect tothealleged risksrelated tothecontrol (or,inother words, theabuse) ofthe
hormones atissue(both natural andsynthetic), wefurther notethateventhough aMember would seem
tobeabletotakeintoaccount risksarising fromdifficulties ofinspecting, sampling ortesting which
arespecific toaparticular substance inaparticular food, the"relevant inspection, sampling andtesting
methods" referred toinArticle 5.2,donotseem tocover thegeneral problem ofcontrol (such asthe
problem ofensuring theobservance ofgood practice) which canexistforanysubstance. Therisks
related tothegeneral problem ofcontrol donotseem tobespecific tothesubstance atissue butto
theeconomic orsocial incidence related toasubstance oritsparticular use(such aseconomic incentives
forabuse). These non-scientific factors should, therefore, notbetaken intoaccount inriskassessment
butinriskmanagement .Moreover, evenifthesefactors could betaken intoaccount inariskassessment,
wenotethattheEuropean Communities hasnotprovided convincing evidence thatthecontrol (orthe
prevention ofabuse) ofthehormones indispute ismore difficult thanthecontrol ofother veterinary
drugs theuseofwhich itallows. Ithasneither provided evidence thatcontrol would bemore difficult
under aregime where thehormones indispute wereallowed under specific conditions thanunder the
current ECregime where thehormones indispute when usedasgrowth promoters arebanned. The
experts advising thePanel made clear thatthepotential forabuse under bothregimes would be
comparable, some noting thatabuse would probably occur more frequently under aregime where the
466However, wenote, inthisrespect, thestatements made bysome ofthescientific experts advising thePanel thateven
ifgood practice isnotfollowed theuseofthefivehormones atissue willinmany cases stillbesafe(seeanswers byexperts
toPanel Question 17,paras. 6.171-176, inparticular theanswers byDr.Arnold, Dr.McLean andDr.Ritter andopinions
ofDr.McLean, Dr.Randell andDr.Arnold, Transcripts ofjointmeeting withexperts of17February 1997, respectively
atparas. 3,26and166). Wealsorecall theconclusions reached byJECFA thattheMRLs (i.e.,thelevels which areset
onthebasisofgood practice) itestablished forzeranol andtrenbolone arefarhigher thanthesafety levels forthese hormones.
467Seepara. 4.186.
468Seepara. 8.108.WT/DS48/R/CAN
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hormones arebanned compared tooneallowing thecontrolled useofprescribed products in
predetermined dosages withwell-defined educational programmes, goodcommunication between the
different actors involved andappropriate penalties formisuse.469Inthiscontext, wenote, therefore,
thatbanning theuseofasubstance doesnotnecessarily offerbetter protection ofhuman health than
other means ofregulating itsuse.
8.150 Inthisrespect, wefinally notethatforthethree natural hormones indispute, theEuropean
Communities has,forcontrol purposes, adopted MRLs andthereby accepted tolerance levels which
arehigher thanthe"zero residue" levelreflected inthemeasures indispute.470Insodoing, theEuropean
Communities itselfseemingly confirms thescientific conclusions reached inallthescientific evidence
examined above, namely thatresidues ofthese hormones, including when usedasgrowth promoters,
aresafebelow acertain level, andcontradicts theconclusion reflected intheECmeasures indispute,
namely thatonlya"zero residue" levelensures theprotection ofECconsumers.
8.151 Forallthereasons outlined above471,wefindthattheECimport banofmeatandmeatproducts
fromanimals treated withanyofthefivehormones atissueforgrowth promotion purposes, insofar
asitalsoapplies tomeat andmeat products from animals treated withanyofthese hormones in
accordance withgood practice ,isnotbased onanassessment ofthefourth orfifthcategory ofrisks
invoked bytheEuropean Communities.
8.152 Inthesixthgeneral category ofrisksinvoked bytheEuropean Communities (risks arising from
various other parameters), theEuropean Communities argues thatnone ofthestudies itreferred to
aspartofariskassessment proves beyond doubt orconcludes inanunqualified manner thatthepresence
ofresidues ofthehormones indispute inmeat ormeat products present noriskwhatsoever .The
European Communities refers, interalia,totheconclusions ofthe1988 JECFA Report which state
thatresidues arising from thehormones atissue usedasgrowth promoters areonlyunlikely topose
ahazard tohuman health andtothebasicpremise ofJECFA recommendations which aimatestablishing
standards which correspond toanoappreciable ornosignificant riskincrease duetotheexposure
tothesubstances inquestion andnottoazeroriskincrease. TheEuropean Communities apparently
considers,therefore,thatthisresidualrisk,albeitminuteandnotappreciable,constitutestherisk(derived
from ariskassessment )onwhich theECbanisbased inaccordance withArticle 5.1,arguing that,
according toECriskmanagement ,riskother thanzeroisnotacceptable.472
8.153 Canada contests thenotion of"zero risk" andargues thattheEuropean Communities hasset
anunattainable goalindemanding absolute proof thatthere iszeroriskassociated withthehormones
indispute.
8.154 Werecall theconclusions wereached above onburden ofproof, inparticular thattheEuropean
Communities has,withrespect toitsmeasures which deviate frominternational standards, theburden
ofproving theexistence ofariskassessment (and, derived therefrom, anidentifiable risk)onwhich
theECmeasures indispute arebased. Itisnot,inthisdispute, forCanada toprove thatthere isno
risk.
469See,forexample, answers byDr.André andDr.Ritter toPanel Question 14,paras. 6.148 and6.154 andopinions
ofDr.Arnold, Dr.Lucier andDr.André, Transcripts ofthejointmeeting withexperts of17February 1997, paras. 269
and274andof18February 1997, para. 4.68..
470Seepara. 4.68.
471Seeparas. 8.146-8.150.
472Seeparas. 4.82 and4.201.WT/DS48/R/CAN
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8.155 Wefurther notethat,according toscientists advising thePanel, science cannever provide a
certainty, i.e.exclude onceandforallthataspecific substance caneverhaveadverse health effects.473
8.156 InthisrespectwealsonotethatthesixthcategoryofrisksinvokedbytheEuropeanCommunities
is,asstated bythescientific experts advising thePanel474andadmitted bytheEuropean Communities475,
notidentifiable andthat,therefore, these riskscanapriori notbeassessed byscientists (asrequired
inArticle 5.1). Inthissense, these potential risks, which arepresent foranysubstance (also for
substances orusesofsubstances allowed intheEuropean Communities), areonlytheconsequence
ofscience notbeing capable ofassuring thatnoriskswilleverarisefrom asubstance.
8.157 Wefinally notethattheECobjective of"zero risk"cannot beachieved inpractice; noteven
under theECbanitselfsincetheEuropean Communities cannot guarantee thatthereisazeroprobability
thatillegal useofthehormones atissue willoccur. Moreover, this"zero risk" objective cannot, as
further examined below476,inanycasebeachieved forthethree natural hormones indispute since
theEuropean Communities allows theingestion ofthese same hormones occurring endogenously in
meatandother foods aswellastheuseofthese hormones fortherapeutic orzootechnical purposes.
8.158 TheECbanontheuseofthehormones indispute forgrowth promotion purposes is,therefore,
notbased onanassessment ofthesixth andfinal category ofrisks invoked bytheEuropean
Communities.
8.159 Forthese reasons, wefindthattheECimport banofmeatandmeatproducts from animals
treated withanyofthefivehormones atissueforgrowth promotion purposes, insofarasitalsoapplies
tomeatandmeatproducts fromanimals treated withanyofthese hormones inaccordance withgood
practice ,isnotbased onanassessment ofanyofthesixgeneral categories ofrisksinvoked bythe
European Communities.
6. Theprecautionary principle
8.160 TheEuropean Communities alsoinvokes theprecautionary principle insupport ofitsclaim
thatitsmeasures indispute arebased onariskassessment. Totheextent thatthisprinciple could be
considered aspartofcustomary international lawandbeusedtointerpret Articles 5.1and5.2onthe
assessment ofrisks asacustomary ruleofinterpretation ofpublic international law(asthatphrase
isusedinArticle 3.2oftheDSU), weconsider thatthisprinciple would notoverride theexplicit wording
ofArticles 5.1and5.2outlined above, inparticular since theprecautionary principle hasbeen
incorporated andgiven aspecific meaning inArticle 5.7oftheSPSAgreement. Wenote, however,
thattheEuropean Communities hasexplicitly stated inthiscasethatitisnotinvoking Article 5.7.
8.161 Wethusfindthattheprecautionary principle cannot override ourfindings made above, namely
thattheECimport banofmeatandmeatproducts fromanimals treated withanyofthefivehormones
atissue forgrowth promotion purposes, insofarasitalsoapplies tomeatandmeatproducts from
animals treated withanyofthese hormones inaccordance withgood practice ,is,fromasubstantive
point ofview, notbased onariskassessment.
473See,forexample, opinions ofDr.Arnold, para. 6.81andDr.Ritter, para. 6.88. Inthisrespect, wenotethatthe
SPSAgreement explicitly deals withsituations where there isscientific uncertainty regarding risks related toasubstance,
inArticle 5.7(discussed inparas. 8.251 ff.),butthattheEuropean Communities hasnotinvoked thisprovision inthiscase.
474Ibid.
475Seepara. 4.208.
476Seeparas. 8.189 ff.WT/DS48/R/CAN
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8.162 Insummary ,inthissection wehavefound that,evenassuming thattheEuropean Communities
hasdemonstrated theexistence ofariskassessment inaccordance withArticle 5,ithasnotfulfilled
theminimal procedural requirements contained inArticle 5.1tobaseitssanitary measures onarisk
assessment. Wehave alsofound that, even ifitwould have fulfilled these minimal procedural
requirements, theEuropean Communities hasnotmetitsburden ofproving thatitsmeasures indispute,
insofarastheyalsobantheimport ofmeatandmeatproducts from animals treated withanyofthe
fivehormones atissue forgrowth promotion purposes inaccordance withgood practice, are,from
asubstantive point ofview, based onariskassessment. TheECmeasures indispute, insofaras
theyrelate tofiveofthesixhormones atissueforwhich international standards exist, are,therefore,
inconsistent withtherequirements ofArticle 5.1.Thefactthatthesemeasures arenotbased onexisting
international standards (contrary toArticle 3.1)477cannot, therefore, bejustified under Article 3.3which
includes asoneoftherequirements forjustification, consistency withArticle 5.1.TheECmeasures,
insofarastheyrelate tofiveofthesixhormones atissueforwhich international standards exist, are,
therefore, alsoinconsistent withtherequirements ofArticle 3.1.
(c) Articles 5.4to5.6: riskmanagement
8.163 Werecall thatthere isadistinction between riskassessment which isascientific examination
andriskmanagement which involves social value judgments.478Once theriskshavebeenassessed,
i.e.,oncetherisksandtheirprobability ofoccurrence identified, aMember willneedtodecide, on
thebasis ofitsownvalue judgments, whether itcanaccept these risks. Insodoing aMember sets
its"appropriate level ofsanitary protection". Thedetermination andapplication oftheappropriate
levelofprotection byaMember ispartofriskmanagement.
8.164 Werecall thedefinition of"appropriate levelofsanitary protection", namely:
"The level ofprotection deemed appropriate bytheMember establishing asanitary
...measure toprotect human, animal orplantlifeorhealth ..."(paragraph 5ofAnnex
AoftheSPSAgreement; emphasis added).
Wealsonotethewording ofArticle 5.5,further examined below:
"...intheapplication oftheconcept ofappropriate level ofsanitary ...protection
against riskstohuman lifeorhealth, ortoanimal andplantlifeorhealth, eachMember
shallavoid ..."
Guided bythewording ofthese provisions andtheobject andpurposes oftheSPSAgreement, we
consider thatifthereisnoscientific evidence ofanidentifiable risk,thereisnobasisonwhich toadopt
ameasure toachieve alevelofsanitary protection under theSPSAgreement, except asprovided in
Article 5.7. Ifthiswere notthecase, i.e.,ifaMember could adopt alevel ofprotection and
implementing sanitary measures evenifitdidnotprovide scientific evidence ofanidentifiable risk,
noeffect would begiven totheobligation contained inArticle 5tobasesanitary measures onan
assessment ofrisks. Thisapproach would undermine thewording andobject andpurpose oftheSPS
Agreement.
8.165 Wehavefound above479thattheEuropean Communities hasnotprovided evidence ofan
identifiable riskrelated tothepresence offiveofthesixhormones atissue forwhich international
477Seepara. 8.80.
478Seeparas. 8.94 ff.
479Seepara. 8.140.WT/DS48/R/CAN
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standards existwhen thesehormones areusedforgrowth promotion purposes inaccordance withgood
practice. Accordingly, theEuropean Communities hasnotestablished theexistence ofanyidentifiable
riskagainst which theECmeasures atissue, insofarastheyalsobantheuseofthefivehormones
when usedasgrowth promoters inaccordance withgood practice, canprotect human lifeorhealth.
Since weconsidered above480thattheadoption ofasanitary measure presupposes theexistence ofan
identifiable risk(except asprovided inArticle 5.7), itisnotpossible fortheEuropean Communities
tobantheuseofthese hormones asgrowth promoters inaccordance withgood practice .
8.166 However,evenifwewouldhavefoundthattheEuropeanCommunitiesmetitsburdenofproving
thatitsmeasures arebased onanassessment ofrisksinaccordance withArticles 5.1and5.2andeven
if,forthatreason, theEuropean Communities could haveadopted ameasure toachieve itsappropriate
levelofprotection against theserisks, therewould stillbeaneedtoexamine whether thedetermination
andapplication ofthislevelofprotection isconsistent withArticles 5.4to5.6.Wewill,therefore,
nextexamine these provisions.
8.167 Thepartiestothisdisputeseemtoagreethattheestablishmentofan"appropriatelevelofsanitary
protection" byaMember isasovereign act,namely, asthedefinition inparagraph 5ofAnnex Aof
theSPSAgreement provides, thelevelofprotection "deemed appropriate bytheMember establishing
asanitary ...measure" (emphasis added). Asoutlined above481,wenote,however, thatMembers have
agreed, inexercising theirsovereign righttosettheirappropriate levels ofprotection, toobserve the
provisions oftheSPSAgreement, inparticular Articles 5.4and5.5thereof. Furthermore, inchoosing
ameasure toachieve thatappropriate levelofprotection Members haveagreed toobserve theprovisions
ofArticles 2,5.1to5.3and5.6.
8.168 Wefinally recall ourfindings reached above onthespecific burden ofproof under Article 3.3.482
Inparticular, wefound thattheburden ofproving thattherequirements imposed byArticle 3.3(inter
alia,consistency withArticle 5)aremet,inorder tojustify asanitary measure which deviates from
aninternational standard, restswiththeMember imposing thatmeasure. Since theECmeasures
examined inthissection (relating toallhormones indispute other thanMGA) arenotbased onexisting
international standards andneedtobejustified under theexceptions provided forinArticle 3.3,the
European Communities bears theburden ofproving thatthedetermination andapplication ofitslevel
ofprotection isconsistent withArticles 5.4to5.6.
(i) Article 5.4: minimizing trade effects
8.169 Article 5.4provides thefollowing:
"Members should ,when determining theappropriate levelofsanitary orphytosanitary
protection, takeintoaccount theobjective ofminimizing negative trade effects"
(emphasis added).
Guided bythewording ofArticle 5.4,inparticular thewords "should" (not"shall") and"objective",
weconsider thatthisprovision oftheSPSAgreement doesnotimpose anobligation. However, this
objectiveofminimizingnegativetradeeffectshasnonethelesstobetakenintoaccountintheinterpretation
ofother provisions oftheSPSAgreement.
480Seepara. 8.164.
481Seeparas. 8.164 ff.
482Seeparas. 8.88 ff.WT/DS48/R/CAN
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(ii) Article 5.5: distinctions inlevels ofprotection
8.170 Article 5.5provides thefollowing:
"With theobjective ofachieving consistency intheapplication oftheconcept of
appropriate level ofsanitary orphytosanitary protection against risks tohuman life
orhealth, ortoanimal andplant lifeorhealth, eachMember shall avoid arbitrary
orunjustifiable distinctions inthelevels itconsiders tobeappropriate indifferent
situations, ifsuchdistinctions result indiscrimination oradisguised restriction on
international trade.Members shallcooperate intheCommittee, inaccordance with
paragraphs 1,2and3ofArticle 12,todevelop guidelines tofurther thepractical
implementation ofthisprovision. Indeveloping theguidelines, theCommittee shall
takeintoaccount allrelevant factors, including theexceptional character ofhuman
health riskstowhich people voluntarily expose themselves" (emphasis added).
8.171 Wenote, inthisrespect, thebasic obligations contained inArticle 2.3:
"Members shallensure thattheirsanitary andphytosanitary measures donotarbitrarily
orunjustifiably discriminate between Members where identical orsimilar conditions
prevail ,including between theirownterritory andthatofother Members. Sanitary
andphytosanitary measures shallnotbeapplied inamanner which would constitute
adisguised restriction oninternational trade"(emphasis added).
Article 2.3deals, ingeneral terms, withsanitary measures which discriminate between Members or
which areapplied inamanner which would constitute adisguised restriction oninternational trade.
Article 5.5,ontheother hand, deals more specifically withdistinctions inlevels ofprotection (which
willnormally bereflected inoneormoresanitary measures) which result indiscrimination oradisguised
restriction oninternational trade.
8.172 Weconsider thatthefirstpartofthefirstsentence ofArticle 5.5("Withtheobjective ofachieving
consistency intheapplication oftheconcept ofappropriate levelofsanitary orphytosanitary protection
against riskstohuman lifeorhealth, ortoanimal andplantlifeorhealth ...";emphasis added), unlike
thesecond part, doesnotimpose anobligation upon Members. Consistency isnotimposed asan
obligation butasanobjective which nonetheless hastobetaken intoaccount intheinterpretation of
Article 5.5.
8.173 Wefurther notethattheCommittee onSanitary andPhytosanitary Measures, established by
Article 12oftheSPSAgreement to"provide aregular forum forconsultations", hasbeengiven a
mandate byArticle 5.5,second sentence, to"develop guidelines tofurther thepractical implementation
ofthisprovision" and,insodoing, needs to"take intoaccount allrelevant factors, including the
exceptional character ofhuman health riskstowhich people voluntarily expose themselves". Nosuch
guidelines havetodatebeendeveloped. However, considering themandatory wording ofthesecond
partofthefirstsentence ofArticle 5.5("each Member shallavoid arbitrary orunjustifiable distinctions
inthelevels itconsiders tobeappropriate indifferent situations ...";emphasis added) andtheexistence
ofthebasicobligations contained inArticle 2.3483,wefindthatthelackofguidelines bytheCommittee
innowaylimits thelegally binding nature ofthesecond partofthefirstsentence ofArticle 5.5.
8.174 Canada argues thattheEuropean Communities failstojustify thefollowing differences in
regulatory treatment: (i)abanonnatural andsynthetic hormones when usedforgrowth promotion
purposes asopposed tonotsetting anylimitforresidues ofthenatural hormones present endogenously
483Seepara. 8.171.WT/DS48/R/CAN
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inuntreated meat andother foods (such asmilk, cabbage, broccoli oreggs) andresidues ofthese
hormones when usedfortherapeutic orzootechnical purposes; and(ii)abanonthehormones indispute
when usedforgrowth promotion purposes asopposed toallowing theuseofantimicrobial growth
promoters asfeedadditives tolivestock (inparticular thesubstances carbadox, olaquindox and
avoparcin)484andotherveterinarydrugsastherapeuticagents(e.g.,benzylpenicillin,carazolol,ivermectin
andorganophosphourus compounds).485During thePanel proceedings Canada focused thediscussion
ofitsclaim under Article 5.5tothedifference intreatment between thesixhormones indispute and
twoofthethree antimicrobial growth promoters, namely carbadox andolaquindox.486
8.175 TheEuropean Communities rejects these claims, arguing thatitdoesnotmake distinctions
initslevels ofprotection fordifferent situations andthat,evenifitweretomake suchdistinctions,
thesedistinctionsarejustifiedanddonotresultindiscriminationoradisguisedrestrictiononinternational
trade.487
Thethree elements contained inArticle 5.5
8.176 WenextexaminetheelementsthatmustbeassessedtodetermineifaMember'ssanitarymeasure
doesnotconform totherequirements ofthesecond partofthefirstsentence ofArticle 5.5.Therelevant
partofArticle 5.5reads asfollows:
"each Member shallavoid arbitrary orunjustifiable distinctions inthelevels itconsiders
tobeappropriate indifferent situations, ifsuchdistinctions result indiscrimination
oradisguised restriction oninternational trade".
8.177 Thefirstelement contained inArticle 5.5isthattheMember concerned adopts different
appropriate levels ofsanitary protection in"different situations". Thesecond element isthatthe
distinction inlevels ofprotection forthedifferent situations is"arbitrary orunjustifiable". Thethird
element isthatthedistinction inlevels ofprotection results in"discrimination oradisguised restriction
oninternational trade". Inorder tofindasanitary measure tobeinconsistent withArticle 5.5allthree
elements needtobepresent.
8.178 Astothefirstelement ,thewords "different situations" havebeeninterpreted bytheparties
asfollows. TheEuropean Communities argues that"different situations" onlycovers different situations
forthesame residue orfordifferent residues where theadverse health effect isthesame.488According
totheEuropean Communities, "different situations" cannot mean thatthesamelevelofprotection must
beapplied tosimilar health hazards, whatever theirnature orseverity, coming fromsimilar substances.
Canada submits that"different situations" captures allthedifferent sanitary risksposed tohuman health
contemplated bytheSPSAgreement. Inthealternative, Canada argues thatattheveryleastthescope
of"different situations" encompasses similar risksandsimilar products .489
484Seeparas. 4.245, 4.246 and4.249.
485Seeparas. 4.250, 4.252, 4.255 and4.256.
486TheEuropean Communities informed thePanel thatavoparcin, thethird antimicrobial agent mentioned byCanada,
hasbeen withdrawn from theECmarket following adecision oftheECCouncil of26February 1996 (seepara. 4.266).
487Seepara. 4.282.
488Seepara. 4.179.
489Seepara. 4.272.WT/DS48/R/CAN
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8.179 Wenotethatbothparties indispute agree thatthescope of"different situations" contained
inArticle 5.5includes situations which dealwiththesame substance aswellassituations which
involve thesame adverse health effect.Forthisreason, considering thelackofguidelines bythe
Committee onSanitary andPhytosanitary Measures andwithout further defining orlimiting thescope
of"different situations", wefindthat,forthepurposes ofthisdispute, wecancompare situations where
thesame substance orthesame adverse health effect isinvolved as"different situations" inthesense
ofArticle 5.5.Forthesakeofclarity inthisparticular case, wewillhereafter refertosuch"different
situations" as"comparable situations" since these situations needtobecompared forthepurposes of
Article 5.5andare,therefore, "comparable".
8.180 Thesecond element contained inArticle 5.5isthatthedistinction inlevels ofprotection for
comparable situations is"arbitrary orunjustifiable".
8.181 Canada argues thatthephrase "each Member shallavoid arbitrary orunjustifiable distinctions
inthelevels itconsiders tobeappropriate" (emphasis added) indicates thatonlysome distinctions are
tobeavoided, i.e.,those thatarearbitrary orunjustifiable. Canada submits thatdistinctions maybe
justified when theseverity oftheadverse health effects posed bydissimilar risks aresignificantly
different. However, according toCanada, suchadistinction would bearbitrary andunjustifiable if
theriskscompared involve adverse health effects ofcomparable severity.490TheEuropean Communities
argues thatArticle 5.5clearly states that"arbitrary orunjustifiable" distinctions aretobeavoided if,
andonlyif,theyresult indiscrimination oradisguised restriction ontrade. Iftheydonotresult in
discrimination oradisguised restriction ontrade, theEuropean Communities concludes, theyarenot
prohibited byArticle 5.5.491
8.182 Thethirdelement contained inArticle 5.5isthatthedistinction inlevelofprotection results
in"discrimination oradisguised restriction oninternational trade".
8.183 Canada submits thatadisguised restriction canbefound when additional factors notrelevant
totheprotection ofhealth leadtotheintroduction ofmeasures thataremore restrictive thannecessary
tomeetlegitimate sanitary concerns, albeit presented intheguise ofasanitary measure. Without this
discipline ofArticle 5.5therewould, according toCanada, beample scope forgovernments tosuccumb
topolitical pressures toprotect certain domestic interests, without regard totheirimpact oninternational
trade, through theirdecisions regarding acceptable levels ofsanitary protection.492TheEuropean
Communities argues thatthemeasures indispute donotresult indiscrimination andthatthefactthat
sanitary measures affect imports isnotasufficient reason toclaim thattheyrestrict trade, orevenless,
thattheydiscriminate.493
8.184 Wenote, firstofall,therelation between thisthirdelement of"discrimination oradisguised
restriction oninternational trade" inArticle 5.5andthebasic obligations contained inArticle 2.3of
theSPSAgreement providing that:
"Members shallensure thattheirsanitary andphytosanitary measures donotarbitrarily
orunjustifiably discriminate between Members where identical orsimilar conditions
prevail, including between theirownterritory andthatofother Members. Sanitary
490Seepara. 4.274.
491Seepara. 4.282.
492Seepara. 4.275.
493Seeparas. 4.39 and4.305.WT/DS48/R/CAN
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andphytosanitary measures shallnotbeapplied inamanner which would constitute
adisguised restriction oninternational trade"(emphasis added).
Wealsonotetherelation between these twoprovisions andthelanguage ofthechapeau ofArticle XX
ofGATT which reads asfollows:
"Subject totherequirement thatsuchmeasures arenotapplied inamanner which would
constitute ameans ofarbitrary orunjustifiable discrimination between thecountries
where thesame conditions prevail, oradisguised restriction oninternational trade,
nothing inthisAgreement shallbeconstrued toprevent theadoption orenforcement
byanycontracting party ofmeasures: ...."(emphasis added).
8.185 With respect tothemeaning of"discrimination" and"adisguised restriction oninternational
trade" werecall theconclusions reached bytheAppellate Body initsReport on"United States -
Standards forReformulated andConventional Gasoline" where theterms "arbitrary orunjustifiable
discrimination" and"adisguised restriction oninternational trade", contained inthechapeau of
Article XXofGATT, were examined asfollows:
"'Arbitrary discrimination ','unjustifiable discrimination 'and'disguised restriction '
oninternational trade may, accordingly, bereadside-by-side; theyimpart meaning
tooneanother. Itisclear tousthat'disguised restriction 'includes disguised
discrimination ininternational trade. Itisequally clearthatconcealed orunannounced
restriction ordiscrimination ininternational trade doesnotexhaust themeaning of
'disguised restriction '.Weconsider that'disguised restriction ',whatever elseitcovers,
mayproperly bereadasembracing restrictions amounting toarbitrary orunjustifiable
discrimination ininternational tradetaken under theguise ofameasure formally within
theterms ofanexception listed inArticle XX. Putinasomewhat different manner,
thekinds ofconsiderations pertinent indeciding whether theapplication ofaparticular
measure amounts to'arbitrary orunjustifiable discrimination ',mayalsobetaken into
account indetermining thepresence ofa'disguised restriction 'oninternational trade.
Thefundamental theme istobefound inthepurpose andobject ofavoiding abuse or
illegitimate useoftheexceptions tosubstantive rulesavailable inArticle XX"(original
emphasis).494
8.186 Wefurther recall theAppellate Body Report on"Japan -Taxes onAlcoholic Beverages" where
theAppellate Body found thatforaninternal taxmeasure tobeinconsistent withthesecond sentence
ofArticle III:2ofGATT, three separate issues must beaddressed soastogivefullmeaning tothe
textandcontext ofthisprovision: (i)theproducts needtobe"directly competitive orsubstitutable";
(ii)theyneedtobe"notsimilarly taxed"; and(iii)thedissimilar taxation needs tobe"applied ...so
astoafford protection todomestic production".495TheAppellate Body found thatthepanel haderred
inblurring thedistinction between thesecond andthirdissuebyequating dissimilar taxation (i.e.,tax
difference above ademinimis level) withtheseparate anddistinct requirement ofdemonstrating that
thetaxmeasure "affords protection todomestic production".496TheAppellate Body thenconcluded
thefollowing:
494Appellate Body Report on"United States -Standards forReformulated andConventional Gasoline", adopted on20
May 1996, WT/DS2/AB/R, p.25.
495Appellate Body Report on"Japan -Taxes onAlcoholic Beverages", adopted on1November 1996, WT/DS8/AB/R,
p.24.
496Panel Report on"Japan -Taxes onAlcoholic Beverages", adopted on1November 1996, WT/DS8/R, paras. 6.33-34
and7.1(ii).WT/DS48/R/CAN
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"Aspreviously stated, afinding that'directly competitive orsubstitutable products '
are'notsimilarly taxed'isnecessary tofindaviolation ofArticle III:2, second sentence.
Yetthisisnotenough. Thedissimilar taxation mustbemore thandeminimis .Itmay
besomuch more thatitwillbeclear fromthatverydifferential thatthedissimilar
taxation wasapplied "soastoafford protection". Insome cases, thatmaybeenough
toshowaviolation .Inthiscase,thePanel concluded thatitwasenough. Yetinother
cases, there maybeother factors thatwillbejustasrelevant ormore relevant to
demonstrating thatthedissimilar taxation atissue wasapplied 'soastoafford
protection '...And, inevery case,acareful, objective analysis, mustbedoneofeach
andallrelevant factsandallrelevant circumstances todetermine 'theexistence of
protective taxation '.Although thePanel blurred itslegal reasoning inthisrespect,
nevertheless weconclude thatitreasoned correctly thatinthiscase, theLiquor Tax
Lawisnotincompliance withArticle III:2" (emphasis added).497
8.187 Weconsider thereasoning inbothAppellate Body Reports tobeequally relevant tothe
relationship between thethree elements contained inArticle 5.5.Allthree elements impart meaning
tooneanother. Nevertheless, inorder togiveeffect toallthree elements contained inArticle 5.5
andgiving fullmeaning tothetextandcontext ofthisprovision, weconsider thatallthree elements
needtobedistinguished andaddressed separately. However, wealsoagree thatinsome cases where
aMemberenacts,forcomparablesituations,sanitarymeasureswhichreflectdifferentlevelsofprotection,
thesignificance ofthedifference inlevels ofprotection combined withthearbitrariness thereof may
besufficient toconclude thatthisdifference inlevels ofprotection "result[s] indiscrimination ora
disguised restriction oninternational trade" inthesense ofArticle 5.5(inlinewiththeargument that
themagnitude oftheverydifferential ofadissimilar taxation maybeenough toconclude thatadissimilar
taxation isapplied soastoafford protection, asprovided forinthesecond sentence ofArticle III:2
ofGATT).
8.188 Wenextexamine, inlightofthethreeelements ofArticle 5.5outlined above, thedistinctions
inlevels ofsanitary protection allegedly made bytheEuropean Communities which havebeeninvoked
byCanada. Inorder toconduct ourconsideration ofthisdispute under Article 5.5inthemostefficient
manner, wefirstaddress thealleged differences intreatment provided bytheEuropean Communities
forthenatural hormones indispute .Inthisexamination wecompare thetreatment ofthese hormones
when usedasgrowth promoters withboththetreatment ofthese hormones occurring endogenously
inmeatandother foods (such asmilk, cabbage, broccoli oreggs) andwhen usedfortherapeutic or
zootechnical purposes. Inasecond step,weaddress thealleged differences intreatment provided by
theEuropean Communities forthenatural hormones indispute asopposed tothatofthesynthetic
hormones atissue.Inathird step,weaddress thealleged differences intreatment provided bythe
European Communities forallhormones indispute (other thanMGA) when usedasgrowth promoters
asopposed tothatforsome antimicrobial growth promoters, namely carbadox andolaquindox .
Natural hormones forgrowth promotion compared to(i)those occurring endogenously
inmeat andother foods, and(ii)those fortherapeutic orzootechnical purposes
1. Comparable situations withdifferent levels ofsanitary protection
8.189 Thisexamination involves acomparison ofthelevels ofprotection forthesame substance ,
namely, respectively, oestradiol-17 ,testosterone andprogesterone, indifferent situations depending
ontheorigin oruseofthatsubstance. Since wehavefound above thatwecancompare situations
where thesame substance isinvolved as"different" situations (which werefer toas"comparable"
497Appellate Body Report onJapan -"Taxes onAlcoholic Beverages", adopted on1November 1996, WT/DS8/AB/R,
p.30.WT/DS48/R/CAN
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situations forthepurposes ofthisdispute) inthesense ofArticle 5.5498,wefindthatthetreatment
ofthethree natural hormones indispute when usedforgrowth promotion purposes asopposed tothe
treatment ofthesehormones which (i)occur endogenously inmeatandother foods and(ii)which have
beenadministered fortherapeutic orzootechnical purposes, constitute comparable situations inthe
sense ofArticle 5.5.
8.190 TheEuropean Communities argues thattheorigin ofthese hormones (whether endogenously
producedorexogenouslyadministered)causesthesehormonestobedifferent,claimingthatthehormones
present endogenously inmeat andother foods haveformed partofthehuman dietforcenturies.499
Wenote,however, thattheEuropean Communities didnotsubmit anyevidence insupport ofitsclaim
thatthese hormones havedifferent effects. Moreover, allscientific experts advising thePanel have
concluded thatresidues ofthethree natural hormones present endogenously inmeatandother foods
oradministered fortherapeutic orzootechnical purposes arequalitatively thesame astheresidues of
thesehormones administered forgrowth promotion andthatifanydifferences between thesehormones
could exist(e.g., differences inpathways taken ormetabolites), these differences would inanyevent
nothaveconsequences forthepotential adverse effects ofthese hormones.500Therefore, evenifthese
hormones would notbetotally identical substances, theypose, inanyevent, thesame adverse health
effect andcan,therefore, according toourfinding made above501,beconsidered ascomparable situations
forthepurposes ofArticle 5.5.
8.191 Wenextexamine whether theEuropean Communities hasadopted adifferent levelofprotection
forthese comparable situations.
8.192 Withrespect tothethreenatural hormones administered forgrowth promotion purposes ,the
European Communities argues thatitslevel ofsanitary protection isconcerned onlywithadded
hormones; inother words, theEuropean Communities doesnotconsider thatitisacceptable toexpose
consumers toanyhormones intheirfoodoverandabove thelevels which occur innature, asanysuch
additional exposure could beahazard tohealth.502
8.193 Theappropriate levelofprotection setbytheEuropean Communities fornatural hormones
present endogenously inmeatandother foods oradministered fortherapeutic orzootechnical purposes
isanunlimited residue level.503Inother words, theEuropean Communities hasnotadopted any
maximum residue level forthese categories ofnatural hormones.504With respect tooestradiol-17
whenusedfortherapeuticorzootechnicalpurposes,thisunlimitedresiduelevelofprotectionhasrecently
beenconfirmed bytheEuropean Communities when itadopted theconclusions reached inthe1988
JECFA Report andclassified thishormone, when usedfortherapeutic orzootechnical purposes, as
498Seepara. 8.179.
499Seepara. 4.84.
500Seeanswers byexperts toPanel Questions 2and4,paras. 6.21-6.30 and6.39-6.49 andopinions ofallexperts advising
thePanel toanoralquestion asked bytheUSrepresentative atthejointmeeting withexperts of17February 1997, Transcripts,
paras. 77,79,84,95and87.
501Seepara. 8.179.
502Ibid.
503Seepara. 4.242.
504With respect tohormones administered fortherapeutic treatment, theEuropean Communities argues thatinpractice
theresidues ofthese hormones willnotbeingested byconsumers because animals undergoing suchtreatment arenotallowed
tobeslaughtered. However, thefactisthattheEuropean Communities hasdecided thatforresidues ofthese hormones
theadoption ofMRLs isunnecessary andhasthusnotsetanyresidue limit(seepara. 8.193 infine).WT/DS48/R/CAN
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asubstance forwhich MRLs areunnecessary.505With respect tothetwoother natural hormones in
dispute, progesterone andtestosterone, when usedfortherapeutic orzootechnical purposes, nofinal
decision hasasyetbeentaken bythecompetent ECauthorities.506
8.194 Wethusfindthatthelevelofprotection adopted bytheEuropean Communities forthethree
natural hormones indispute when usedforgrowth promotion andthatadopted forthesame hormones
(i)occurringendogenouslyinmeatandotherfoodsand(ii)usedfortherapeuticorzootechnicalpurposes,
isdifferent ("noresidue" levelasopposed toanunlimited residue level) andthat,therefore, distinctions
inlevels ofprotection forthesecomparable situations existinthesense ofthefirstelement ofArticle 5.5.
2. "Arbitrary orunjustifiable" difference inlevels ofsanitary protection
8.195 Wenextexamine whether these twodistinctions inlevels ofprotection are"arbitrary or
unjustifiable". Wefirstaddress thedistinction made between thethree natural hormones when used
asgrowth promoters andthesame hormones occurring endogenously inmeatandother foods. We
thenexamine thedistinction made between thethreenatural hormones when usedasgrowth promoters
andthesame hormones when usedfortherapeutic orzootechnical purposes.
8.196 Natural hormones usedasgrowth promoters asopposed tothose occurring endogenously in
meatandother foods. TheEuropean Communities hasnotprovided anyreasons, other thanthose
addressed above, whyithasadopted adifferent levelofprotection fortheresidues ofthesetwocategories
ofnatural hormones. TheEuropean Communities has,inparticular, notprovided anyevidence that
theriskrelated tothenatural hormones usedasgrowth promoters isinanywayhigher thantherisk
related tonatural endogenous hormones. Wealsorecall thattheexperts advising thePanel concluded
thatbothcategories ofhormones (either exogenously administered toanimals orendogenously present
inanimals, meat, other foods orhuman beings) posethesame potential adverse effects.507
8.197 Inthisrespect wefurther recall theconclusion reached inthe1988 JECFA Report thatthe
totalresidue levelofnatural hormones inmeatfromtreated animals (i.e.,thecombination ofnatural
hormonesendogenouslypresentandthoseaddedforgrowthpromotion)fallswellwithinthephysiological
range oflevels found inmeatfromuntreated animals, which levels varyaccording tothesexandage
oftheanimal.508Wealsonotethat,according todatasubmitted tothePanel, theresidue levelofnatural
hormones inmany natural products (such aseggsandsoyaoil)ismuch higher thanthelevelofresidues
ofthesehormones administered forgrowth promotion aswellasthetotalresidue levelofthesehormones
505Seeanswer byDr.Arnold toPanel Question 5,para. 6.54.
506Ibid.,para. 6.53.
507Seepara. 8.190 and,inparticular, thefootnote thereto.
508Seepara. 8.65. Thisconclusion hasnotbeencontested byeither theparties orexperts advising thePanel. Forexample,
according todatasubmitted tothePanel (theaccuracy ofwhich hasnotbeen disputed bytheparties), theresidue level of
testosterone in500grams ofuntreated bullmeatis1,560 nanograms asopposed to35nanograms in500grams ofmeatfrom
aheifer implanted withtestosterone.WT/DS48/R/CAN
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intreated meat.509Inthisrespect, wefurther notethatCodex hasalsoestablished MRLs forsubstances
which endogenously occur innatural products.510
8.198 With respect tothepotential difficulties indetecting thepresence ofnatural hormones used
asgrowth promoters, werefertoourconclusions reached above511,namely thatonlyunder thecurrent
ECregime (aban)doestheproblem ariseofhowtodistinguish between endogenous andadded natural
hormones whereas under aregime where onewould allow theuseofthesehormones (with, forexample,
anMRL ortolerance levelforallnatural hormones) therewould benoneedtodistinguish endogenous
from added natural hormones. Wealsonotethat,inanyevent, theproblem ofdetection would be
thesame forbothnatural hormones usedasgrowth promoters andthose occurring endogenously in
meat andother foods (since thescientific experts stated thatbotharequalitatively thesame512)and
can,therefore, notjustify adifferent treatment.
8.199 Wefinally notethatevenifsome formofjustification could bededuced fromthearguments
submitted bytheEuropean Communities, suchcould not,inanyevent, justify sosignificant adifference
inlevels ofprotection between a"noresidue" level fornatural hormones administered forgrowth
promotion andanunlimited residue levelfornatural hormones endogenously present inmeatandother
foods.
8.200 WethusfindthattheEuropeanCommunitieshasnotmetitsburdenofprovingthatthedistinction
itmakes inlevels ofprotection forresidues ofthethreenatural hormones indispute when administered
forgrowth promotion purposes andresidues ofthesame natural hormones present endogenously in
meatandother foods isjustifiable andthat,therefore, thisparticular distinction inlevels ofprotection
is"arbitrary orunjustifiable" inthesense ofthesecond element contained inArticle 5.5.
8.201 Natural hormones usedasgrowth promoters asopposed tothose usedfortherapeutic or
zootechnical purposes. TheEuropean Communities argues thattheuseofthenatural hormones for
therapeutic andzootechnical purposes occurs onasmall scale, issubject toverystrictconditions (such
asadministration byaveterinarian andstrict withdrawal periods) andnormally onlyinvolves cattle
intended forbreeding, notforslaughter; whereas theuseofthesehormones asgrowth promoters occurs
onamuch larger scaleandismore difficult andcostly tocontrol. These differences inuseandcontrol,
theEuropean Communities argues, ensure thatanyriskrelated tothetherapeutic orzootechnical use
ofthese hormones isprevented andthatinpractice alevelof"noresidue" isachieved, asisthecase
fortheuseofthese hormones asgrowth promoters. Forthese reasons, theEuropean Communities
concludes, thedistinction inlevels ofprotection isjustified.513
8.202 Wenotethat,according toscientific experts advising thePanel, zootechnical useofthese
hormones canoccur onalarge scale andatregular intervals, namely each year foroestrus
509Forexample, according todatasubmitted tothePanel (theaccuracy ofwhich hasnotbeen disputed bytheparties),
theresidue level ofoestradiol-17 equivalents ina50to60grams hen'seggis1,750 nanograms (in10mlofsoybean oil,
20,000 nanograms) asopposed to11.4nanograms in500grams ofsteermeatimplanted withoestradiol-17 and75nanograms
in500grams ofuntreated cowmeat. Inother words, theoestrogen content of1hen'seggisequivalent to76.5kgofimplanted
steer beef. Inthisrespect, wealsonotethatapre-puberty male child naturally produces 41,000 nanograms ofoestrogens
in24hours, anadult man136,000 nanograms andapregnant women 20,000,000 nanograms.
510Forexample, MRLs have been adopted byCodex for(naturally occurring) cyanide incassava flour andinGari(a
cassava product).
511Seepara. 8.148.
512Seepara. 8.190.
513Seepara. 4.242.WT/DS48/R/CAN
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synchronization ofentire herds.514Moreover, evenwhen these hormones areusedfortherapeutic or
zootechnical purposes, allparties andscientific experts advising thePanel agree thatsome residue level,
albeit avery small one,willalways remain inthemeat when thetreated animal iseventually
slaughtered.515Therefore, a"noresidue" levelcannot inpractice beachieved when these hormones
areusedfortherapeutic orzootechnical purposes.
8.203 However, since wehavealready concluded thatthedifference inlevels ofprotection imposed
intheEuropean Communities forthethreenatural hormones when usedforgrowth promotion purposes
asopposed tothose present endogenously inmeat andother foods cannot bejustified, weconsider
itunnecessary todecide whether ornotthedistinction made bytheEuropean Communities between
natural hormones usedasgrowth promoters andthose usedfortherapeutic orzootechnical purposes
isjustified.
3. Difference which results in"discrimination oradisguised restriction oninternational
trade"
8.204 Wenextexamine whether thedifference inlevels ofprotection between residues ofthethree
natural hormones indispute when administered forgrowth promotion purposes andresidues ofthe
same natural hormones present endogenously inmeatandother foods, results indiscrimination ora
disguised restriction oninternational trade within themeaning ofthethirdelement ofArticle 5.5.516
8.205 Werecalltheconsiderationsmadeaboveontherelationshipbetweenthethreeelementscontained
inArticle 5.5.517Werecall, inparticular, thatinsome cases thesignificance ofthedifference inlevels
ofprotection forcomparable situations combined withthearbitrariness thereof maybesufficient to
conclude thatthisdifference inlevels ofprotection results in"discrimination oradisguised restriction
oninternational trade".
8.206 Inthiscase, wenote, firstly, thesignificance ofthedifference inlevels ofprotection forthe
three natural hormones indispute when administered forgrowth promotion purposes andresidues of
thesamehormonespresentendogenouslyinmeatandotherfoods,namelya"noresidue"levelasopposed
toanunlimited residue level. Werecall, secondly, thattheEuropean Communities hasnotprovided
anyplausible justification forthissignificant difference. Wenote, finally, thatthisdifference inlevels
ofprotection results inanimport ban(onmeatandmeatproducts treated withanyofthethree natural
hormones indispute forgrowth promotion purposes) which restricts international trade. Forthese
reasons, wefindthatthedifference inlevels ofprotection imposed bytheEuropean Communities for
thethree natural hormones indispute when administered forgrowth promotion purposes andthose
present endogenously inmeatandother foods, results in"discrimination oradisguised restriction on
international trade" inthesense ofArticle 5.5.
8.207 Weconsider thatthisfinding isfurther supported bytwoadditional factors. Firstly, werecall
some oftheobjectives (other thantheprotection ofhuman health) thattheEuropean Communities
hadinmind when enacting ormaintaining theECbanontheuseofthenatural hormones forgrowth
514Seeanswers byexperts toPanel Questions 19and20,paras. 6.182-6.192.
515Ibid. Seealsoopinions ofallexperts advising thePanel onaquestion bytheUSrepresentative atthejointmeeting
withexperts of17February 1997, Transcripts, paras. 90,91,93and95andanswers byexperts toPanel Question 3,
paras. 6.31-6.38.
516Since wemade nofinding onthejustifiability ofthedifference inlevels ofprotection forthenatural hormones indispute
when administered asgrowth promoters andthose administered fortherapeutic orzootechnical purposes, wedonotaddress,
forthatadditional difference inlevels ofprotection, thethird element ofArticle 5.5.
517Seeparas. 8.185-8.187.WT/DS48/R/CAN
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promotion purposes, asstated inthepreambles oftheECmeasures indispute518andinthereports
oftheEuropean Parliament andtheopinions oftheECEconomic andSocial Committee referred to
bytheEuropeanCommunities519,namelyharmonizingtheregulatoryschemesofthedifferentECMember
States, thereby removing competitive distortions andbarriers tointra-Community trade inbeef, and
bringing about anincrease intheconsumption ofbeef, thereby reducing theinternal beefsurpluses
andproviding more favourable treatment todomestic producers.
8.208 Secondly, wenotethatbefore theECbancame intoforce, thepercentage ofanimals treated
withanyofthehormones indispute wassignificantly lower intheEuropean Communities thanin
Canada. Atthattime, according totheEuropean Communities, onlyfourorfiveECmember States
allowed theuseofsome ofthesehormones. Onemember State(theUnited Kingdom) which hasreplied
totheEC'srequest forinformation onthisissue, indicated that"anecdotal evidence suggests thatgrowth
promoting hormones mayhavebeenused[in]upto40%ofUKcattle prior totheban".520Onthe
other hand, according toatable provided byCanada, based onafiveyearaverage, thenumber of
animalstreatedwithanyofthesegrowthpromotinghormonesinCanadawasapproximately76.8percent
ofthose entering thefoodchain. Bybanning theinternal saleandimport ofmeattreated withnatural
hormones forgrowth promotion purposes (which represents asignificantly higher proportion ofthe
totalCanadian meatsupply thanofthetotalEuropean Communities meatsupply) butcontinuing to
allow anylevel ofresidues ofthese natural hormones present endogenously inmeat, theEuropean
Communities favoured theconsumption ofdomestic meatand,therefore, defactodiscriminates against
Canadian meatinfavour ofECmeat. Inthissense, thedifference inlevels ofprotection intheEuropean
Communities forresidues ofhormones present endogenously inmeat andother foods andresidues
ofthesamenatural hormones when administered forgrowth promotion purposes could besaidtoresult
in"discrimination oradisguised restriction oninternational trade".
8.209 WethusfindthattheEuropean Communities hasnotmetitsburden ofjustifying thedistinction
itmakes inlevels ofprotection forresidues ofthethree natural hormones indispute administered for
growth promotion purposes andresidues ofthesame natural hormones present endogenously inmeat
andother foods, inlightofthethree elements contained inArticle 5.5,andthat,therefore, theEC
measures indispute, insofarastheyrelate tothethree natural hormones atissue, areinconsistent
withtherequirements imposed inArticle 5.5.
518Such aspreambles 5and6toDirective 88/146/EEC which state, inter alia,thefollowing:
"Whereas theadministration tofarmanimals ofcertain substances having ahormonal action isatpresent
regulated indifferent ways intheMember States; ...whereas thisdivergence distorts theconditions of
competition inproducts thatarethesubject ofcommon market organizations andisaserious barrier to
intra-Community trade;
Whereas these distortions ofcompetition andbarriers totrade must therefore beremoved byensuring
thatallconsumers areabletobuytheproducts inquestion under largely identical conditions ofsupply
andthatthese products correspond totheiranxieties andexpectations inthebestpossible manner; whereas
suchacourse ofaction isbound tobring about anincrease inconsumption oftheproduct inquestion".
519Such astheNielsen Report of1981, theCollins Reports of1985 and1989 andthePimenta Report of1989 ofthe
European Parliament andtheopinions oftheECEconomic andSocial Committee of1981 and1984, outlined inparas. 4.14,
4.19and4.20. SeealsoJudgment oftheCourt ofJustice oftheEuropean Communities inthecaseC-331/88, "The Queen
v.TheMinister forAgriculture, Fisheries andFood andtheSecretary ofState forHealth, exparte: Fedesa andOthers",
1990, ECR I-4023, atp.I-4065, para. 25:"...thematerial made available totheCourt ...shows thatthepossibility ofa
reduction insurpluses wasindeed taken intoconsideration during theprocess leading totheadoption ofthedirective [in
casu, Directive 88/146/EEC]...".
520Seepara. 4.16, footnote 30.WT/DS48/R/CAN
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Synthetic hormones forgrowth promotion compared tonatural hormones
8.210 Wenextexamine thealleged different treatment provided bytheEuropean Communities for,
ontheonehand, twoofthethreesynthetic hormones indispute forwhich international standards exist
(zeranol andtrenbolone)521and, ontheother hand, thenatural hormones indispute occurring
endogenously inmeatandother foods.522
1. Comparable situations withdifferent levels ofsanitary protection
8.211 Inthisexaminationwecomparedifferentsubstances,namely,respectively,zeranolandoestradiol-
17andtrenboloneandtestosterone.Asoutlinedabove523,bothsynthetichormonesatissueareproduced
tomimic oneofthenatural hormones indispute (zeranol mimics oestradiol-17 andtrenbolone mimics
testosterone). However, bothparties inthisdispute andtheexperts advising thePanel agree thatthe
situations thuscompared involve atleastthesame adverse health effect,namely carcinogenicity.524
8.212 Since wedecided above thatwecancompare situations where thesame adverse health effect
isinvolved as"different" situations (which werefer toas"comparable" situations forthepurposes
ofthisdispute) inthesense ofArticle 5.5525,wefindthatthetreatment ofzeranol andtrenbolone and
thetreatment ofthenatural hormones indispute which occur endogenously inmeatandother foods,
arecomparable situations inthesense ofthefirstelement ofArticle 5.5.
8.213 Wenextexamine whether theEuropean Communities hasadopted different levels ofprotection
forthese comparable situations.
8.214 With respect tozeranol andtrenbolone, theEuropean Communities adopted a"noresidue"
levelasitsappropriate levelofprotection.526Asoutlined above527,thelevelofprotection intheEuropean
Communities forthenatural hormones present endogenously inmeatandother foods isanunlimited
residue level.
8.215 Wethusfindthatthelevels ofprotection adopted bytheEuropean Communities forresidues
ofzeranol andtrenbolone andthatforresidues ofthenatural hormones indispute which occur
endogenously inmeatandotherfoods aredifferent ("noresidue" levelasopposed toanunlimited residue
level) andthat,therefore, adistinction inlevels ofprotection forthese comparable situations exists
inthesense ofthefirstelement ofArticle 5.5.
521Asmentioned above, thehormone MGA, forwhich nointernational standard exists, willbedealt withinaseparate
section inparagraphs 8.253 ff.
522Sincewemadenofindingonthedifferenceinlevelsofprotectionfornaturalhormonesadministeredasgrowthpromoters
andthose administered fortherapeutic orzootechnical purposes (seepara. 8.203), wedonotaddress thealleged difference
inlevels ofprotection forsynthetic hormones administered asgrowth promoters andnatural hormones administered for
therapeutic orzootechnical purposes.
523Seepara. 8.4.
524Seeanswers byexperts toPanel Question 4,paras. 6.36-6.46. SeealsoTranscripts ofjointmeeting withexperts of
17February 1997, pp.62-63.
525Seepara. 8.179.
526Seepara. 4.56.
527Seepara. 8.193.WT/DS48/R/CAN
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2. "Arbitrary orunjustifiable" difference inlevels ofsanitary protection
8.216 Wenextexamine whether thisdifference inlevels ofprotection is"arbitrary orunjustifiable".
TheEuropean Communities hasnotprovided convincing evidence thatthesynthetic hormones (which
mimic thenatural hormones) areinherently more dangerous thanthenatural hormones.528Most of
theevidence referred tobytheEuropean Communities toprove potential risksrelates tothenatural
hormones, inparticular oestradiol-17 .529According tothescientists advising thePanel, synthetic
hormones canalsobebetter detected andcontrolled thannatural hormones.530Moreover, thefactthat
ADIs andMRLs existforzeranol andtrenbolone andnotforthenatural hormones doesnot,according
totheexperts advising thePanel, persemean thatthelatter areinherently saferthantheformer since
theinternational standards forbothsynthetic andnatural hormones reflect essentially thesame level
ofprotection, namely a"noappreciable risk"level.531Therefore, eveniftherecould bevalidreasons
tosubject thenatural hormones toatreatment different fromthesynthetic hormones532,theEuropean
Communities hasnotprovided justification forsosignificant adifference inlevels ofprotection as
between a"noresidue" level(forthesynthetic hormones atissue) andanunlimited residue level(for
thenatural hormones endogenously present inmeatandother foods). Werecall, inparticular, that
theEuropean Communities hasnotprovided evidence thattheuseofzeranol ortrenbolone forgrowth
promotion purposes inaccordance withgood practice (forexample, theCodex MRLs) isunsafe.533
Inother words, ithasnotsubmitted anyjustification foradopting a"noresidue" level, instead ofthe
Codex MRLs.
8.217 WethusfindthattheEuropean Communities hasnotmetitsburden ofjustifying thedistinction
itmakes inlevels ofprotection forzeranol andtrenbolone andthenatural hormones indispute which
occur endogenously inmeatandother foods. Forthese reasons, wefindthatthedifference inlevels
ofprotection thusmade bytheEuropean Communities is"arbitrary orunjustifiable" inthesense of
thesecond element contained inArticle 5.5.
3. Difference which results in"discrimination oradisguised restriction oninternational
trade"
8.218 Werecalltheconsiderationsmadeaboveontherelationshipbetweenthethreeelementscontained
inArticle 5.5.534Werecall, inparticular, thatinsome cases thesignificance ofthedifference inlevels
ofprotection forcomparable situations combined withthearbitrariness thereof maybesufficient to
528Seealsoanswers byexperts toPanel Question 4,paras. 6.39-6.49 andTranscripts ofthejointmeeting withexperts
of17February 1997, para. 348,where Dr.Lucier stated thatinhisopinion residues ofsynthetic hormones areofmore
concernthanthoseofnaturalhormonesbecausetherisksrelatedtothenaturalhormonesarealreadythereduetothoseoccurring
endogenouslyinthebody,whereasresiduesofthesynthetichormonesarenewtothebody.Thisdifferencedoesnot,however,
relate totheinherent characteristics ofbothcategories ofhormones, buttothefactthatonecategory occurs endogenously
inhumans, whereas theother does not.
529Seeparas. 4.160-4.163.
530Seeanswers byexperts toPanel Question 22,paras. 6.198-6.201.
531See,forexample, opinion ofDr.Randell, para. 6.75. Wealsonote, inthisrespect, theopinion ofDr.Arnold,
para. 6.44: "Thepotential risksarising fromother thanhormonal actions [related tothesynthetic hormones] werequalitatively
different. These riskswere assessed during thereview andapproval process, andtheapproved conditions ofuseeliminated
allunacceptable risks".
532See,forexample, theCodex standards which haveadopted MRLs forthesynthetic hormones andnotforthenatural
hormones.
533Seepara. 8.140.
534Seeparas. 8.185-8.187.WT/DS48/R/CAN
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conclude thatthisdifference inlevels ofprotection results in"discrimination oradisguised restriction
oninternational trade".
8.219 Inthiscase,wenote,firstly, thesignificance ofthedifference inlevels ofprotection forzeranol
andtrenbolone andthatforthenatural hormones indispute which occur endogenously inmeatand
other foods, namely a"noresidue" levelasopposed toanunlimited residue level. Werecall, secondly,
thattheEuropeanCommunitieshasnotprovidedanyplausiblejustificationforthissignificantdifference.
Wenote, finally, thatthisdifference inlevels ofprotection results inanimport ban(onmeatandmeat
products treated withzeranol ortrenbolone) which restricts international trade. Forthese reasons,
wefindthatthedifference inlevels ofprotection imposed bytheEuropean Communities forzeranol
andtrenbolone andthatforthenatural hormones indispute which occur endogenously inmeatand
other foods, results in"discrimination oradisguised restriction oninternational trade" inthesense
ofArticle 5.5.
8.220 Weconsider thatthisfinding isfurther supported bythetwoadditional factors outlined above535,
which areequally validforthedistinction inlevels ofprotection made bytheEuropean Communities
forzeranol andtrenbolone andthenatural hormones indispute which occur endogenously inmeat
andother foods.
8.221 WethusfindthattheEuropean Communities hasnotmetitsburden ofjustifying thedistinction
itmakes inlevels ofprotection forzeranol andtrenbolone andthenatural hormones indispute which
occur endogenously inmeatandother foods, inlightofthethree elements contained inArticle 5.5,
andthat,therefore, theECmeasures indispute, insofarastheyrelate tozeranol andtrenbolone,
areinconsistent withtherequirements imposed inArticle 5.5.
Thehormones indispute compared tocarbadox andolaquindox
8.222 Wenextexamine thealleged different treatment provided bytheEuropean Communities for
fiveofthesixhormones indispute (allbutMGA) when usedforgrowth promotion purposes and
carbadox andolaquindox. Werecall thattheseagents areantimicrobial growth promoters usedasfeed
additives inswine production.536
1. Comparable situations withdifferent levels ofsanitary protection
8.223 Inthisexamination wecompare different substances .However, bothparties inthisdispute
andtheexperts advising thePanel agree thatthesituations thuscompared involve thesame adverse
health effect,namely carcinogenicity.537
8.224 Since wehavefound above thatwecancompare situations where thesameadverse health effect
isinvolved as"different" situations (which werefer toas"comparable" situations forthepurposes
ofthisdispute) inthesense ofArticle 5.5538,wefindthatthetreatment ofthefivehormones atissue
when usedasgrowth promoters asopposed tothatofcarbadox andolaquindox arecomparable situations
inthesense ofthefirstelement ofArticle 5.5.
535Seeparas. 8.207 and8.208.
536Seeparas. 4.245-4.246.
537Seeanswers byexperts toPanel Question 11,paras. 6.127-6.135.
538Seepara. 8.179.WT/DS48/R/CAN
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8.225 Wenextexamine whether theEuropean Communities hasadopted adifferent levelofprotection
forthese comparable situations.
8.226 Canada argues thattheEClevelofprotection forthehormones atissuewhen usedforgrowth
promotion isdifferent fromthatforcarbadox andolaquindox: intheformer situation, thesubstances
arebanned andthelevelis"zero residue"; inthelatter, thesubstance isallowed foruseintheEuropean
Communities without theimposition ofanMRL.539
8.227 Withrespecttothehormonesindisputewhenusedforgrowthpromotionpurposes,theEuropean
Communities adopted a"noresidue" levelasitsappropriate levelofprotection.540With respect to
carbadox andolaquindox, theEuropean Communities argues that,eventhough these substances are
allowed, strict controls, specific characteristics ofthese substances andthewaytheyareadministered,
ensure thatnoresidue levels willremain intreated pigswhen slaughtered andthat,therefore, inthe
European Communities inpractice thesame levelofprotection applies tocarbadox andolaquindox
astheleveladopted forthehormones indispute, namely a"noresidue" level.541
8.228 WenotethattheEuropean Communities allows theuseofcarbadox andolaquindox asgrowth
promoters inpigsandhasnotsetanyMRL forthese substances. TheEuropean Communities thus,
inprinciple, accepts anunlimited residue levelofthese substances inporkmeat. Moreover, werecall
that,contrary towhattheEuropean Communities argues, a"noresidue" levelcannot beachieved in
practice when useofthesubstance concerned isallowed (even under strict conditions) since there will
always besome residue levelofthesubstance orametabolite, albeit averysmall one,leftinthemeat,
evenafteralongperiod oftime.542Weconsider, forthese reasons, thattheEuropean Communities
cannot reasonably claim thatitslevelofprotection forcarbadox orolaquindox isa"noresidue" level.
8.229 WethusfindthatthelevelofprotectionadoptedbytheEuropeanCommunitiesforthehormones
atissue when usedforgrowth promotion purposes asopposed tothatadopted forcarbadox and
olaquindox isdifferent (a"noresidue" levelasopposed toanunlimited residue level) andthat,therefore,
adistinction inthelevels ofprotection forthese comparable situations exists inthesense ofthefirst
element ofArticle 5.5.
2. "Arbitrary orunjustifiable" difference inlevels ofsanitary protection
8.230 Wenextexamine whether thisdistinction inlevels ofprotection is"arbitrary orunjustifiable"
inthesense ofthesecond element ofArticle 5.5.
8.231 Canada argues thattherisksrelated tocarbadox andolaquindox areatleastasserious asthose
related totheuseofthehormones indispute asgrowth promoters.543Itrefers tothe36thJECFA Report
of1991 which could notsetanADIforcarbadox butdidadopt MRLs foroneofitsmetabolites and
wasunable toallocate anADIforolaquindox, asopposed tothe32nd and34thJECFA Reports of
1988and1989which onlyadopted ADIs andMRLs forzeranol andtrenbolone andconsidered MRLs
forthethree natural hormones tobeunnecessary. Canada submits thatnone ofthearguments put
forward bytheEuropean Communities justifies astricter levelofprotection forthehormones indispute
539Seepara. 4.245.
540Seepara. 4.56.
541Seepara. 4.284.
542Seeopinions ofallexperts advising thePanel inTranscripts ofthejointmeeting withexperts of17February 1997,
paras. 90,91,93and95andanswers toPanel Question 3,paras. 6.31-6.38.
543Seepara. 4.273.WT/DS48/R/CAN
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(which,accordingtoCanada,aresafe)thanthelevelofprotectionforcarbadoxorolaquindox(substances
which, according toCanada, mayposeserious risks).544
8.232 TheEuropean Communities claims thatthedistinction inlevels ofprotection isjustified on
thefollowing grounds: (i)carbadox andolaquindox arenothormones; (ii)carbadox andolaquindox
onlyindirectly actasgrowth promoters bycombating thedevelopment ofbacteria andbyaiding the
intestinal floraofpiglets, thereby alsoexerting preventive therapeutic effects (whereas thehormones
directly actasgrowth promoters andhave nopreventive therapeutic action when usedasgrowth
promoters); (iii)carbadox andolaquindox areonlycommercially available inprepared feedstuffs (not
asinjections orimplants) inpredetermined dosages; (iv)there arenoalternatives tocarbadox or
olaquindox available which havethesame therapeutic action; (v)carbadox cannot beabused since it
onlyhasgrowth promotion effects inpiglets uptofourmonths oldandawithdrawal period ofatleast
28daysisfixed; and(vi)carbadox isusedinsuchsmall quantities andishardly absorbed thatitleaves
practically noresidues atallinmeatdestined forhuman consumption.545
8.233 Wenote, firstofall,thattheEuropean Communities hasnotsubmitted scientific evidence in
support ofthesealleged justifications. Wenextexamine thesixarguments putforward bytheEuropean
Communities inlightoftheopinions oftheexperts advising thePanel andthearguments submitted
byCanada.
8.234 With respect tothefirstECargument, i.e.,thefactthatcarbadox andolaquindox are
antimicrobial agents andnothormones, theEuropean Communities hasnotsubmitted anyreason why
thisdifference could initself justify adifferent regulatory treatment inthelightoftheirpotential
carcinogenic effect. Wethusfindthatthisargument doesnotjustify thedistinction inlevels ofprotection
forthefivehormones atissue when usedasgrowth promoters andcarbadox orolaquindox.
8.235 TheEuropean Communities nextargues thatthefivehormones atissue when usedasgrowth
promoters havenotherapeutic effect onanimals asopposed tocarbadox andolaquindox which combat
thedevelopment ofbacteria andaidtheintestinal floraofpiglets.546Inthisrespect, Canada submits
thatthere isnoreason tosubject consumers tohigher riskfromresidues ofveterinary drugs usedfor
therapeutic purposes asopposed tothose usedforother purposes, suchasgrowth promotion.547We
note, moreover, that,according toscientific experts advising thePanel, thehormones atissue when
administered asgrowth promoters mayalsohavebeneficial effects (such asimproved composition of
thecarcass upon treatment interms ofmore leanmeat andlessfat).548Finally, werecall thatthe
hormones atissueare,effectively, usedfortherapeutic purposes andthatsuchuseofthethree natural
hormones indispute isallowed intheEuropean Communities. Forthese reasons, weconsider that
boththehormones indispute andcarbadox andolaquindox mayhavetherapeutic effects andthusfind
thatthesecond ECargument doesnotjustify thedistinction inlevels ofprotection forthefivehormones
atissue when usedasgrowth promoters andcarbadox orolaquindox.
8.236 With respect tothethirdECargument, i.e.,thefactthatcarbadox andolaquindox areonly
commercially available inprepared feedstuffs (notasinjections orimplants) inpredetermined dosages
544Seepara. 4.275.
545Seepara. 4.284(i).
546Seepara. 4.284(ii).
547Seepara. 4.274.
548Seeanswers byexperts toPanel Question 2,paras. 6.21-6.31, inparticular answers byDr.Arnold, Dr.McLean and
Dr.Ritter. Seealsoopinion ofDr.Lucier, Transcripts ofthejointmeeting withexperts of18February 1997, para. 742,
where hefeels unable, asascientist, tocompare therisks related tothehormones withtheir potential benefits.WT/DS48/R/CAN
Page248
andare,therefore, allegedly lessopenforabuse549,wenotethatoneofthescientific experts advising
thePanel stated thatinjections orimplants aremore accurate andreliable methods toadminister growth
promoters thanadditives infeedstuffs (because ofcarry-over risksfromtreated tountreated feed).550
Theexperts alsostated thatadditives infeedstuffs poseadditional risksinthattheymayharmthepersons
handling thefeedstuff.551Wealsorecall that, according totheexperts advising thePanel, the
commerciallyavailableproductscontaininganyofthefivehormonesatissueforimplantationorinjection
alsocontain predetermined dosages ofthese hormones.552WethusfindthatthethirdECargument
doesnotjustify thedistinction inlevels ofprotection forthefivehormones atissuewhen usedasgrowth
promoters andcarbadox orolaquindox.
8.237 Addressing thefourth ECargument thatthere arenoalternatives tocarbadox orolaquindox
available which havethesame therapeutic action, wenotethatoneoftheexperts advising thePanel
stated thatthere arereadily available alternatives, suchasoxytetracycline.553Wethusfindthatthis
ECargument doesnotjustify thedistinction inlevels ofprotection forthefivehormones atissuewhen
usedasgrowth promoters andcarbadox orolaquindox.
8.238 Werecall thefifthECargument, i.e.,thatthepotential forabuse isallegedly smaller for
carbadox thanforthehormones atissuesincetheformer onlyexertgrowth promotion effects inpiglets
uptofourmonths andaresubject toastrictwithdrawal period.554Wenotethat,according totheexperts
advising thePanel, thereisnoguarantee thatthepiglets treated withcarbadox willnotbeslaughtered.
Residues ofthissubstance oritsmetabolites maythusenter thefoodchain. Wealsonotethat,asis
thecasefortheuseofcarbadox intheEuropean Communities, theuseofthehormones atissue as
growth promoters mayalsobemade subject tostrict conditions. Wethusconsider thattheEuropean
Communities hasnotsubmitted evidence proving thatcarbadox canbemore easily controlled than
thefivehormones atissueandfind,therefore, thatthefifthECargument doesnotjustify thedistinction
inlevels ofprotection forthefivehormones atissue when usedasgrowth promoters andcarbadox.
8.239 TheEuropean Communities further argues thatcarbadox isusedinsuchsmall quantities and
ishardly absorbed sothatitleaves practically noresidues atallinmeat destined forhuman
consumption.555Werecall that,according totheexperts advising thePanel, onceasubstance hasbeen
administered toananimal there willalways besome residue levelofthissubstance orametabolite
left,albeit averysmall one,inthemeatofthatanimal.556Wefurther notethat,according tothe36th
JECFA Report of1991which assessed therisksrelated tocarbadox andolaquindox, notonlycarbadox
itself(forwhich noADIs could beestablished) butalsooneofitsmetabolites, quinoxaline-2-carboxylic
acid(forwhich anMRL wasadopted) maypresent ahealth risk. Wefinally notethat,according to
549Seepara. 6.26.
550Seeanswers byexperts toPanel Question 21,paras. 6.193-6.197, inparticular answer byDr.McLean atpara. 6.196.
551Seeanswers byexperts toPanel Question 21,paras. 6.130-6.197, inparticular answers byDr.André andDr.McLean
atparas. 6.193 and6.196.
552Seeanswers byexperts toPanel Question 15,paras. 6.155-6.165.
553Seeopinion ofDr.Arnold, para. 6.129.
554Seepara. 4.284.
555Seepara. 4.240.
556Seepara. 8.202 and,particularly withrespect tocarbadox, opinion ofDr.Lucier, Transcripts ofthejointmeeting
withexperts of18February 1997, para. 575.WT/DS48/R/CAN
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thescientific experts557,residue levels ofthehormones atissue willalsorapidly decline after
administration toananimal oringestion byhumans. Forthese reasons, wefindthatthesixth EC
argument doesnotjustify thedistinction inlevels ofprotection forthefivehormones atissue when
usedasgrowth promoters andcarbadox orolaquindox.
8.240 TheEuropean Communities finally submits thatitauthorizes theuseofabout 10,000 to15,000
veterinary medicinal products andthatthefactthatCanada limits itsclaim under Article 5.5toonly
one[two] substances, proves thattheEuropean Communities hasalready achieved aremarkable degree
ofconsistency initslevels ofsanitary protection. TheEuropean Communities alsoinformed thePanel
thattheECCouncil, bydecision of26February 1996, already tookaction onitsowninitiative toreview
bothcarbadox andolaquindox. Weconsider thatthese arguments donotjustify thedistinction which
iscurrently stillmade bytheEuropean Communities inlevels ofprotection forthefivehormones at
issuewhen usedasgrowth promoters andcarbadox orolaquindox. Onthecontrary, these arguments
suggest anacknowledgment bytheEuropean Communities thatthedistinction inlevels ofprotection
itcurrently makes maynotbejustified andwillbereviewed.
8.241 Fortheabove reasons, wefindthattheEuropean Communities hasnotmetitsburden of
justifying thedistinction itmakes inlevels ofprotection forthefivehormones atissue when usedas
growth promoters andcarbadox orolaquindox andthattheEuropean Communities has,apriori ,not
metitsburden ofjustifying sosignificant adistinction between a"noresidue" levelforthehormones
atissue when usedasgrowth promoters andanunlimited residue levelforcarbadox andolaquindox.
Wefind,therefore, thatthedistinction inlevels ofprotection thusmade bytheEuropean Communities
is"arbitrary orunjustifiable" inthesense ofthesecond element contained inArticle 5.5.
3. Difference which results in"discrimination oradisguised restriction oninternational
trade"
8.242 Canada submits thatthedistinction made bytheEuropean Communities inlevels ofprotection
forthehormones atissue when usedasgrowth promoters andcarbadox andolaquindox constitutes
discriminationandadisguisedrestrictiononinternationaltradeinthesenseofthethirdelementcontained
inArticle 5.5forthefollowing reasons: (i)Canadian beeffromcattle treated withthegrowth promoting
hormones atissue poses nogreater risktoECconsumers thanECmeat treated withcarbadox or
olaquindox and(ii)theECbancausing thedistinction inlevels ofprotection isbased onadditional
factors notrelevant totheprotection ofhealth (such asharmonizing theregulatory schemes oftheEC
member States thereby removing competitive distortions andbarriers tointra-Community trade, meeting
consumeranxietiesandexpectationsandbringingaboutanincreaseintheconsumptionofmeatproducts).
According toCanada, theEuropean Communities succumbed topolitical pressures toprotect certain
domestic interests without regard totheirimpact oninternational trade.558
8.243 Werecall thatthethree elements contained inArticle 5.5allimpart meaning tooneanother
andthatinsome cases thesignificance ofthedifference inlevels ofsanitary protection forcomparable
situations combined withthearbitrariness ofthereof, maybesufficient toconclude thatthisdifference
inlevels ofprotection results in"discrimination oradisguised restriction oninternational trade".559
8.244 Inthiscase, wenote, firstly, thesignificance ofthedifference inlevels ofprotection forthe
fivehormones atissue when usedasgrowth promoters andcarbadox andolaquindox, namely a"no
residue" level asopposed toanunlimited residue level. Werecall, secondly, thattheEuropean
557See,forexample, opinion ofDr.Lucier, para. 6.36andDr.Arnold, Transcripts ofthejointmeeting withexperts
of17February 1997, para. 79.
558Seepara. 4.183.
559Seeparas. 8.185-8.187.WT/DS48/R/CAN
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Communitieshasnotprovidedanyplausiblejustificationforthissignificantdifference.Wenote,finally,
thatthisdifference inlevels ofprotection results inanimport ban(onmeatandmeatproducts treated
withanyofthese fivehormones atissue) which restricts international trade. Forthese reasons, we
findthatthedifference inlevels ofprotection imposed bytheEuropean Communities forthefive
hormones atissue when used asgrowth promoters andcarbadox andolaquindox, results in
"discrimination oradisguised restriction oninternational trade" inthesense ofArticle 5.5.
8.245 Weconsider thatthisfinding isfurther supported bythetwoadditional factors outlined above560,
which areequally validforthedistinction inlevels ofprotection made bytheEuropean Communities
forthefivehormones atissue when usedasgrowth promoters andcarbadox andolaquindox.
8.246 Wefinally notethatthere isanother factor which indicates thatthedistinction intreatment
made bytheEuropean Communities forthehormones atissue when usedasgrowth promoters and
carbadox andolaquindox results in"discrimination oradisguised restriction oninternational trade".
Thatisthefactthatthehormones atissue, which arebanned intheEuropean Communities, areused
forgrowth promotion inthebovine meatsector where theEuropean Communities seemingly wants
tolimitsupplies561andisarguably lessconcerned withinternational competitiveness, whereas carbadox
andolaquindox, which areallowed intheEuropean Communities, areusedforgrowth promotion in
theporkmeatsectorwheretheEuropeanCommunitieshasnodomesticsurplusesandwhereinternational
competitiveness isahigher priority.562
8.247 WethusfindthattheEuropean Communities hasnotmetitsburden ofjustifying thedistinction
itmakes inlevels ofprotection forfiveofthesixhormones atissue(allbutMGA) when usedasgrowth
promoters andcarbadox orolaquindox, inlightofthethree elements contained inArticle 5.5,and
that,therefore, theECmeasures indispute, insofarastheyrelate tothese fivehormones indispute,
areinconsistent withtherequirements imposed inArticle 5.5.
8.248 Insummary, inthissection wehavefound thattheECmeasures indispute, bothinsofaras
theyrelate tothetwosynthetic hormones (zeranol andtrenbolone) andthethree natural hormones at
issue forwhich international standards exist, areinconsistent withtherequirements contained in
Article 5.5.ThefactthattheECmeasures indispute arenotbased onexisting international standards
(contrary toArticle 3.1)can,forthatreason, notbejustified onthebasis ofArticle 3.3. TheEC
measures, insofarastheyrelate tofiveofthesixhormones atissueforwhich international standards
exist, are,therefore, alsoinconsistent withtherequirements ofArticle 3.1.
(iii) Article 5.6:measures notmore trade restrictive thanrequired toachieve
theappropriate levelofprotection
8.249 Article 5.6reads asfollows:
"Withoutprejudicetoparagraph2ofArticle3,whenestablishingormaintainingsanitary
orphytosanitary measures toachieve theappropriate levelofsanitary orphytosanitary
protection, Members shallensure thatsuchmeasures arenotmore trade-restrictive
thanrequired toachieve theirappropriate levelofsanitary orphytosanitary protection,
taking intoaccount technical andeconomic feasibility".
560Seeparas. 8.207 and8.208.
561Seealsopara. 8.207.
562ThesefactualconsiderationswereprovidedtotheparallelpanelrequestedbytheUnitedStates.However,weconsidered
itappropriate tomention them inthisPanel report aswell(seeourreasoning inpara. 8.19 ).WT/DS48/R/CAN
Page251
Afootnote toArticle 5.6states thefollowing:
"Forpurposes ofparagraph 6ofArticle 5,ameasure isnotmore trade-restrictive than
required unless there isanother measure, reasonably available taking intoaccount
technical andeconomic feasibility, thatachieves theappropriate levelofsanitary or
phytosanitary protection andissignificantly lessrestrictive totrade".
8.250 Since wefound above thattheEClevelofprotection reflected intheECmeasures indispute
hasbeenadopted inviolation ofArticle 5.5,wedonotconsider itnecessary tofurther examine whether
these measures arealsomore trade restrictive thanrequired toachieve thatlevel inthesense of
Article 5.6.
(d) Article 5.7: provisional sanitary measures
8.251 Article 5.7reads asfollows:
"Incaseswhere relevant scientific evidence isinsufficient, aMember mayprovisionally
adopt sanitary orphytosanitary measures onthebasisofavailable pertinent information,
including thatfrom therelevant international organizations aswellasfrom sanitary
orphytosanitary measures applied byotherMembers. Insuchcircumstances, Members
shallseektoobtain theadditional information necessary foramoreobjective assessment
ofriskandreview thesanitary orphytosanitary measure accordingly within areasonable
period oftime".
8.252 Werecall ourfinding reached above ontheroleoftheprecautionary principle inthe
SPSAgreement, inparticular thatthisprinciple would notoverride theexplicit wording of
thatAgreement, interalia,because ithasbeenincorporated inaspecific form inArticle 5.7.563In
thisdispute, theEuropean Communities hasexplicitly stated thatitsmeasures arenotprovisional
measures inthesense ofArticle 5.7. Wedo,therefore, notneedtofurther examine thisprovision.
6. Sanitary measures where nointernational standards exist: melengestrol acetate
("MGA")
8.253 Werecall thatwithrespect tothethirdsynthetic hormone indispute, MGA, nointernational
standard exists.564Asoutlined above, theEuropean Communities is,therefore, notunder anobligation
tobaseitssanitary measure inrespect ofthishormone onaninternational standard inaccordance with
Article 3.1.565
8.254 However, eventhough nointernational standard exists forMGA, theECmeasures indispute
relating toMGA stillneedtocomply withtheother provisions oftheSPSAgreement. Canada has
invoked violations ofArticles 2and5.Since Article 2provides forbasic rights andobligations which
arefurther specified inArticle 5,wefirstexamine theconsistency oftheECmeasures indispute relating
563Seepara. 8.161.
564Seepara. 8.73.
565Seeparas. 8.59 ff.WT/DS48/R/CAN
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toMGA withtherequirements ofArticle 5.566Theconsistency oftheECmeasures relating toall
hormones indispute (including MGA) withtherequirements ofArticle 2willbedealtwithbelow.567
(a) Burden ofproof
8.255 Werecall ourfinding reached above onthegeneral burden ofproof under theSPSAgreement568,
inparticular thatfortheobligations imposed bytheSPSAgreement thatarerelevant tothiscase, the
party contesting asanitary measure (incasuCanada) bears theburden ofpresenting aprima faciecase
ofinconsistency withtheSPSAgreement, afterwhich theburden ofproof shifts totheparty imposing
themeasure (incasutheEuropean Communities). Weconsider that,forthereasons mentioned above569,
thisallocation ofevidentiary burden isapplicable totheobligations imposed onMembers under Article
5.Werecall, inparticular, thewording ofArticle 5.1,especially thefirstthree words thereof:
"Members shall ensure thattheirsanitary ...measures arebased onanassessment ...ofthe
risks..."(emphasis added)
andthewording ofthesecond partofthefirstsentence ofArticle 5.5:
"...eachMember shall avoid arbitrary orunjustifiable distinctions inthelevels it
considers tobeappropriate indifferent situations, if..."(emphasis added).
Therefore, inthisdispute Canada hastopresent aprima faciecasethattheECmeasures indispute
relating toMGA areinconsistent withtherequirements ofArticle 5,afterwhich theburden shifts to
theEuropean Communities toprove thatithascomplied withthese requirements.
(b) Articles 5.1to5.3: riskassessment
8.256 Withrespect toArticles 5.1to5.3dealing withtherequirement ofariskassessment ,Canada
argues thattheEuropean Communities hasnotsubmitted anyscientific evidence which could constitute
ariskassessment forthehormone MGA andthattheEuropean Communities has,therefore ,apriori ,
notbased itsmeasures withrespect toMGA onanyriskassessment asrequired byArticle 5.1.570
WefindthatCanada thusmeets itsburden ofpresenting aprima facie caseofinconsistency with
Article 5.1.
8.257 Werecall ourreasoning outlined above ontherequirement oftheexistence ofariskassessment
inaccordance withArticles 5.1to5.3571,inparticular thatwithrespect tothefiveother hormones
indispute weassumed thattheEuropean Communities metitsburden ofdemonstrating theexistence
ofariskassessment since itreferred toseveral scientific reports which appear tomeettheminimum
requirements ofariskassessment.
566Weonlyexamine theconsistency oftheECmeasures relating toMGA withtherequirements contained inArticles 5.1
to5.3and5.5. With respect totheother provisions ofArticle 5werefer toourconsiderations setoutinsection 5which
equally apply totheECmeasures relating toMGA.
567Seepara. 8.274.
568Seeparas. 8.51 ff.
569Seeparas. 8.55-8.57.
570Seepara. 4.122.
571Seeparas. 8.111-8.114.WT/DS48/R/CAN
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8.258 With respect toMGA, wenote, however, thattheEuropean Communities hasnotsubmitted
anyscientific evidence inwhich thepotential foradverse effects onhuman health ofMGA residues
isevaluated. Moreover, thescientists advising thePanel haveatseveral occasions stated thatthey
arenotaware ofanypublicly available scientific study which evaluates thesafety ofMGA572;thestudies
carried outbyCanada areproprietary studies which remain confidential.
8.259 TheEuropean Communities argues thattheECmeasures indispute regulate hormones onthe
basisoftheirphysiological action, notonthebasisofindividual substances andthattheadministration
ofanysubstance having anoestrogenic, androgenic orgestagenic action iscovered bytheECban,
including MGA which hasagestagenic action.573
8.260 Wenote, however, thatwithrespect toallfiveother hormones indispute, JECFA, Codex
andtheEuropean Communities itselfhaveconducted orinvoked riskassessments foreachindividual
substance. Wefurther notethatoneofthebasic principles ofariskassessment appears tobethat
itneeds tobecarried outforeachindividual substance.574Aswasstated inthe1995 ECScientific
Conference:
"Itmust beemphasised thataseparate riskassessment must beconducted oneach
growth promoting substance. Itisnotappropriate toattempt toproduce adetailed
generic riskassessment foraclassofgrowth promoters".575
8.261 WethusfindthattheEuropean Communities hasnotmetitsburden ofdemonstrating the
existence ofariskassessment withrespect toMGA andthat,therefore, theECmeasures indispute,
insofarastheyrelate tothehormone MGA, arenotbased onanassessment ofrisksinaccordance
withArticle 5.
8.262 Werecall, inthisrespect, thattheEuropean Communities hasexplicitly stated thatArticle 5.7,
which deals withcases where relevant scientific evidence isinsufficient andallows aMember totake
provisional sanitary measures, doesnotapply tothemeasures indispute, including those relating to
MGA.576
8.263 Wefurther recall ourreasoning andfindings reached above (with respect tothefiveother
hormones indispute) ontheprocedural andsubstantive requirements aMember mustsatisfy inorder
tobaseitssanitary measures onariskassessment inaccordance withArticles 5.1577.Werecall, in
particular, thattheEuropean Communities has,from aprocedural point ofview, notprovided any
evidence thatthestudies itreferred tohaveactually beentaken intoaccount bythecompetent EC
572See, forexample, statements byDr.Ritter andDr.McLean, Transcripts ofthejoint meeting with experts of
17February 1997, paras. 352and354.
573Seepara. 4.56.
574See,forexample, answer byDr.André toPanel Question 13(para. 6.141) andthepractice inJECFA which only
examines specific substances andthis,mostly, when these substances areusedforspecific purposes. Inparticular, theJoint
FAO/WHO Expert Consultation onResidues ofVeterinary Drugs inFoods (29October -5November 1984; FAO Food
andNutritionPaperNo.32)recommendedthata"...scientificbodyshouldrelyontheadviceofexpertsinveterinarymedicine,
animal science, toxicology, microbiology, immunology, analytical chemistry andrelated sciences, andestablish criteria for
thesafety ofindividual veterinary drug residues asappropriate, taking intoaccount theirpublic health significance, good
animal husbandry anddrugusepractices, thelikelihood ofresidues andtheavailability ofadequate analytical methodology"
(addp.15, emphasis added).
5751995 ECScientific Conference Proceedings, p.250.
576Seepara. 8.252.
577Seeparas. 8.115 ff.WT/DS48/R/CAN
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institutions orarereflected intheECmeasures insuchawaythatthese measures could besaidto
bebased onthese studies. Wefurther recall thattheEuropean Communities hasnotmetitsburden
ofproving thatitsmeasures indispute, insofarastheyalsobantheuseofthefivehormones atissue
forgrowth promotion purposes inaccordance withgoodpractice, are,fromasubstantive pointofview,
based onariskassessment.
8.264 Thesamereasoningappliesapriori totheECmeasureswithrespecttoMGAsincetheEuropean
Communities hasnotsubmitted anystudy inwhich therisksrelated toMGA areassessed. Wethus
findthattheEuropean Communities hasnotmetitsburden ofproviding evidence tothePanel that
itsmeasures indispute, insofarastheyrelate tothehormone MGA, are,either from aprocedural
orasubstantial point ofview, based onariskassessment andthat,therefore, these measures are
inconsistent withtherequirements ofArticle 5.1.
(c) Article 5.5: distinctions inlevels ofprotection
8.265 Evenifwehadfound thattheEuropean Communities metitsburden ofproving thatitsmeasures
relating toMGA arebased onanassessment ofrisksinaccordance withArticles 5.1and5.2andeven
if,forthatreason, theEuropean Communities could haveadopted anappropriate levelofprotection
against these risks, there would stillbeaneedtoexamine whether thedetermination andapplication
ofthislevel ofprotection isconsistent withArticle 5.5.578Inthisrespect, Canada argues thatthe
European Communities failstojustify thefollowing differences inregulatory treatment: (i)abanon
MGA when usedforgrowth promotion purposes asopposed tonotsetting anylimitforresidues of
thenatural hormones present endogenously inuntreated meatandother foods (such asmilk, cabbage,
broccoli oreggs) orusedfortherapeutic orzootechnical purposes; and(ii)abanonMGA when used
forgrowth promotion purposes asopposed toallowing theuseofantimicrobial growth promoters as
feedadditives forlivestock (inparticular carbadox andolaquindox)579.Only withrespect tothelast
mentioned difference intreatment doesCanada explicitly invoke Article 5.5.
8.266 Werefertoparagraphs 4.280-4.285 forthearguments submitted byCanada withrespect to
these distinctions inlightofthethree elements contained inArticle 5.5andfindthatCanada meets
itsburden ofpresenting aprima faciecaseofinconsistency withArticle 5.5.
(i) MGA forgrowth promotion compared tothenatural hormones occurring
endogenously inmeat andother foods
8.267 Werecall ourreasoning andfindings reached above withrespect totheECmeasures indispute
relating tothehormones atissue other thanMGA, inparticular ourfinding thattheEuropean
Communities hasnotmetitsburden ofjustifying thedistinction itmakes inlevels ofprotection for
residues ofzeranol andtrenbolone (twoofthesynthetic hormones indispute) andresidues ofthenatural
hormones indispute which occur endogenously inmeatandother foods, inlightofthethreeelements
contained inArticle 5.5,andthat,therefore, theECmeasures indispute, insofarastheyrelate to
zeranol andtrenbolone, areinconsistent withtherequirements imposed inArticle 5.5.580
8.268 Weconsider thatthisreasoning andthesefindings equally apply totheECmeasures indispute
relating toMGA (thethird synthetic hormone indispute). Firstly, theEuropean Communities has
adopted different levels ofprotection (a"noresidue" limit581asopposed toanunlimited residue level)
578Seepara. 8.166.
579Seeparas. 4.199 and4.275.
580Seepara. 8.221.
581Seepara. 4.56.WT/DS48/R/CAN
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forcomparable situations, incasusituations posing thesameadverse health effect (i.e.,carcinogenicity),
namely forMGA used asagrowth promoter andthenatural hormones indispute which occur
endogenously inmeatandother foods inthesense ofthefirstelement ofArticle 5.5.Secondly, the
European Communities hasnotsubmitted evidence thatthisdifference inlevels ofprotection isjustified
andhasthusnotmetitsburden ofproving thatthisdifference isnot"arbitrary orunjustifiable" in
thesense ofthesecond element ofArticle 5.5.Thirdly, theEuropean Communities hasnotmetits
burden ofrebutting thearguments andevidence submitted byCanada thatthisdifference inlevels of
protection results in"discrimination oradisguised restriction oninternational trade" inthesense of
thethirdelement ofArticle 5.5.
8.269 WethusfindthattheEuropean Communities hasnotmetitsburden ofjustifying thedistinction
itmakes inlevels ofprotection forMGA usedasagrowth promoter andthenatural hormones indispute
whichoccurendogenouslyinmeatandotherfoods,inlightofthethreeelementscontainedinArticle5.5,
andthat,therefore, theECmeasures indispute, alsoinsofarastheyrelate toMGA, areinconsistent
withtherequirements imposed byArticle 5.5.
(ii) MGA forgrowth promotion compared tocarbadox andolaquindox
8.270 Wefurther recall ourreasoning andfindings reached above withrespect totheECmeasures
indispute relating tothehormones atissueother thanMGA, inparticular ourfinding thattheEuropean
Communities hasnotmetitsburden ofjustifying thedistinction itmakes inlevels ofprotection for
residues ofthehormones atissue (other thanMGA) when usedforgrowth promotion purposes and
residues ofcarbadox andolaquindox inlightofthethree elements contained inArticle 5.5andthat,
therefore, theECmeasures indispute, insofarastheyrelate tothehormones indispute (other than
MGA), areinconsistent withtherequirements imposed byArticle 5.5.582
8.271 Weconsider thatthisreasoning andthesefindings equally apply totheECmeasures indispute
relating toMGA. Firstly, theEuropean Communities hasadopted different levels ofprotection (a
"noresidue"limit583asopposedtoanunlimitedresiduelevel)forcomparablesituations,incasusituations
posing thesame adverse health effect (i.e.,carcinogenicity)584,namely forMGA usedasagrowth
promoter andcarbadox andolaquindox inthesense ofthefirstelement ofArticle 5.5.Secondly, the
European Communities hasnotsubmitted anyevidence thatthisdifference inlevels ofprotection is
justified andhasthusnotmetitsburden ofproving thatthisdifference isnot"arbitrary orunjustifiable"
inthesense ofthesecond element ofArticle 5.5. Thirdly, theEuropean Communities hasnotmet
itsburden ofrebutting thearguments andevidence submitted byCanada thatthisdifference inlevels
ofprotection results in"discrimination oradisguised restriction oninternational trade" inthesense
ofthethirdelement ofArticle 5.5.
8.272 WethusfindthattheEuropean Communities hasnotmetitsburden ofjustifying thedistinction
itmakes inlevels ofprotection forMGA usedasagrowth promoter andcarbadox orolaquindox, in
lightofthethree elements contained inArticle 5.5,andthat,forthisreason, alsotheECmeasures
indispute which relate toMGA areinconsistent withtherequirements imposed byArticle 5.5.
8.273 Insummary ,inthissection wehavefound thattheECmeasures indispute relating toMGA
areinconsistent withtherequirements contained inArticles 5.1and5.5.
582Seepara. 8.247.
583Seepara. 4.56.
584Seepara. 4.284.WT/DS48/R/CAN
Page256
7. Article 2:"Basic Rights andObligations"
8.274 Since wehavefound thattheECmeasures indispute areinconsistent withtherequirements
ofArticles 3and5oftheSPSAgreement andconsidering thatArticles 3and5provide formore specific
rights andobligations thanthe"basic rights andobligations" setoutinArticle 2,weseenoneedto
further examine whether theECmeasures indispute alsoviolate Article 2.
E. ARTICLES IIIAND XIOFGATT
8.275 Since wehavefound thattheECmeasures indispute areinconsistent withtherequirements
oftheSPSAgreement, weseenoneedtofurther examine whether theECmeasures indispute are
alsoinconsistent withArticles IIIorXIofGATT.
8.276 Asnoted above inparagraph 8.45, ifwewere tofindaninconsistency withArticle IorIII
ofGATT, wewould thenneedtoexamine whether thisinconsistency could bejustified, asargued
bytheEuropean Communities, under Article XX(b) ofGATT andwould thusnecessarily needtorevert
totheSPSAgreement under which wehave already found inconsistencies. Since theEuropean
Communities hasnotinvoked anydefence under GATT other thanArticle XX(b), aninconsistency
withArticle IorXIofGATT would, therefore, inanyevent, notbejustifiable.
F. CLAIM OFNULLIFICATION AND IMPAIRMENT UNDER ARTICLE XXIII:1(b) OF
GATT
8.277 Since wehavefound thattheECmeasures indispute areinconsistent withspecific provisions
oftheSPSAgreement, weseenoneedtofurther examine whether theECmeasures indispute also
constitute acaseofnullification orimpairment ofabenefit accruing toCanada under theWTO
Agreement pursuant toArticle XXIII:1(b) ofGATT.
G. CONCLUDING REMARKS
8.278 Inorder toavoid anymisunderstanding astothescope andimplications ofthefindings above,
wewould liketostress thatitwasnotourtasktoexamine generally thedesirability ornecessity of
theECCouncil Directives indispute. Theability ofanyMember totakesanitary measures which
donotaffect international trade wasnotatissue inthepresent case. Ourexamination wasconfined
tothose aspects oftheECmeasures thathavebeenraised byCanada, namely theECimport banon
meatandmeatproducts ofbovine origin treated withanyofsixspecific hormones forgrowth promotion
purposes. Itwasfurther limited tothespecific provisions ofGATT andtheSPSAgreement which
havebeeninvoked bytheEuropean Communities insupport ofthisimport ban. Thatisthenecessity
oftheimport ban,which theEuropean Communities strictly construed asasanitary measure, forthe
protection ofhuman lifeorhealth. Likewise, theability ofanyMember toenact measures which are
intended toprotect notconsumer health butother consumer concerns wasnotaddressed. Inthisregard,
weareaware thatinsome countries where theuseofgrowth promoting hormones ispermitted inbeef
production, voluntary labelling schemes operate whereby beeffromanimals which havenotreceived
suchtreatment maybesolabelled.WT/DS48/R/CAN
Page257/258
IX. CONCLUSIONS
9.1 Inlightofthefindings above, wereach thefollowing conclusions:
(i) TheEuropean Communities, bymaintaining sanitary measures which arenotbased
onariskassessment, hasacted inconsistently withtherequirements contained inArticle 5.1
oftheAgreement ontheApplication ofSanitary andPhytosanitary Measures.
(ii) TheEuropean Communities, byadopting arbitrary orunjustifiable distinctions inthe
levels ofsanitary protection itconsiders tobeappropriate indifferent situations which result
indiscrimination oradisguised restriction oninternational trade, hasacted inconsistently with
therequirements contained inArticle 5.5oftheAgreement ontheApplication ofSanitary and
Phytosanitary Measures.
(iii) TheEuropean Communities, bymaintaining sanitary measures which arenotbased
onexisting international standards without justification under Article 3.3oftheAgreement
ontheApplication ofSanitary andPhytosanitary Measures, hasacted inconsistently withthe
requirements contained inArticle 3.1ofthatAgreement.
9.2 Werecommend thattheDispute Settlement Body requests theEuropean Communities tobring
itsmeasures indispute intoconformity withitsobligations under theAgreement ontheApplication
ofSanitary andPhytosanitary Measures.WT/DS48/R/CAN
Page259
ANNEX
PANEL ONEUROPEAN COMMUNITIES -MEASURES CONCERNING MEAT
AND MEAT PRODUCTS (HORMONES) -PANEL ESTABLISHED AT
THE REQUEST OFTHE UNITED STATES
PANEL ONEUROPEAN COMMUNITIES -MEASURES CONCERNING MEAT
AND MEAT PRODUCTS (HORMONES) -PANEL ESTABLISHED AT
THE REQUEST OFCANADA
Transcript oftheJoint Meeting withExperts, heldon
17and18February 1997
First day-17February 1997
Chairman
1. Iwould liketowelcome thescientific experts andtheparties tothisexpert meeting. Letme
startbyinforming youthattheproceedings ofthismeeting arebeing recorded, therefore, when taking
thefloor, representatives andexperts should please usetheirmicrophones. Asindicated inmyletter
of7thofFebruary 1997thePanel decision tojointhetwomeetings withscientific experts stems from
thesimilarities ofthetwocases, asdoesthePanel'sdecision tousethesame scientific experts inboth
cases andtoinvite Canada andtheUnited States toparticipate onequal footing inthemeetings inboth
cases. Inaddition, there istheconsideration thatfrom apractical perspective there willbeaneed
toavoid therepetition ofarguments andofquestions. Irecall thatastotheproceedings inlegalterms,
thecases arenotformally joined. They arejoined forthissession today andtomorrow asahearing
oftheexperts andthedebate withtheexperts. Itendtosaythatthere canonlybeonetruthinthis
matter; wecannot havetwotruths. Thatisthephilosophy weshould address atthismeeting andtake
advantage offullmutual information here. Thepurpose ofthismeeting isthattheexperts canexpand
ontheirwritten briefs andthatourquestions canbeputtothem, views canbechallenged. Iwould
liketotaketheopportunity atthisstage tothank theexperts verydeeply thattheyresponded insuch
ashort period oftimetotherequest ofthepanel. Asyouknow, weareoperating under verystringent
timeconstraints, wehavetoproduce reports withcertain delays andthisputsanenormous pressure
notonlyonusbutalsoonyou. AndIverymuch would liketothank youattheoutset thatyouagreed
mostly towork onthis,Iassume, overChristmas holidays toproduce yoursubstantive reports. These
reports areverysubstantive anditisnotamatter ofrepeating themlinebylinebutreally tohighlight
themain points andthefocus andalsotoputthePanel intoaposition tobefullyinformed about
controversial issues which mayexistherewhich would allow ustomake alegalassessment here.
2. Ialsowould liketostress thattheproceedings areconfidential. Everything which isbeing
saidinthisroom issubject totherules ofdispute settlement. Soit'sconfidential unless release is
permitted byoneoftheparties. Wehadarequest thismorning from theEuropean Community at
aninformal meeting togrant theopportunity tohavetheparties 'experts fromECsidemaking upfront
statements inorder tofullyinform theparties andthePanel inthese proceedings ontheirviews. The
Panel hasdiscussed thisrequest andhascome totheconclusion thatwewould denythisopportunity
forthefollowing reasons. Thismeeting oftwodayswassetupasahearing ofexperts andthepurpose
istoheartheexperts andputquestions totheexperts bymaking useofscientific experts within the
delegations. Itisnotthepurpose ofthismeeting tohearnewevidence which hasnotbeensubmitted
byFebruary 8th.Anditisnotthepurpose ofthismeeting tohaveformal statements bytheparties,
butjustfrom theexperts. Now, thiswillnotexclude thattheexperts which areonthedelegationsWT/DS48/R/CAN
Page260
oftheparties canspeak tothepoint, thattheywould dosowhen timeisgiven tothedelegations and
theyareinaposition toexpand ontheirviews during these interventions. These interventions will
thenagain givetheexperts theopportunity toreacttowhatwassaidfromthedelegations. Inthelight
ofthis,Iwould liketoexplain howwewould liketoproceed today. Wewould firsthavestatements
bytheexperts andIwould liketoinvite youtofocus onyourmainpoints, yourmainarguments, your
mainareas where youseetheissues, themainareas ofcontention andalsowhere youseetheproblems
inyourcolleagues 'reports. After thestatements, followed bytheexpert oftheCodex, there willbe
discussion within thepanel ofexperts. When thisisconcluded, theUnited States willhave the
opportunity toputquestions andtocomment ontheexperts 'views. Thiswillbefollowed bythe
intervention oftheEuropean Community, withthepossibility, asIsaid,tohavestatements byyour
ownexperts anditwillthengotoCanada forthesameproceeding. Andsincewehavetwoproceedings
heremixed, theECwillagain haveanopportunity totakethefloorintheveryend.After thisprocess,
wewould intend togivetheexperts again individually thefloorforafinalstatement where theycould
stress theirviews again andtheirconclusions. ThePanel would thensitintheevening andwewould
thentrytofocus onmore specific questions which from alegalpoint ofviewmaystillnotbeclear
andinthemeeting oftomorrow afternoon weasaPanel would thencome inwithveryspecific questions
totheexperts which westillmayhavetoclarify. Sowehaveageneral debate which inthebeginning
hopefully thatwhich willallow ustofocus onthemainissues andtomorrow theremight beveryspecific
questions here. Thisdoesnotexclude thattoday theparties mayraisespecific questions totheexperts
based ontheirwritten submissions, based ontheanswers tothequestions here. AndIassume that
delegations areprepared todoso.Mylastpoint isplease trytobeshort andtothepoint inallyour
interventions. Please trytoavoid repetitions, repetitious statements, sothatwecangoalong withthe
time. Thisis,Ithink, theendofmyintroduction. Iwould nowliketodeclare openthehearings.
Irepeat thatallthatissaidinthisroom remains confidential under therulesofPanel proceedings and
Iwould propose thefollowing order: Professor McLean, Dr.Arnold, Professor André, Dr.Ritter,
Dr.Lucier andthenDr.Randell astheCodex expert. Iaminformed thattheslidemachine hasnot
beeninstalled, soifsomebody would liketoshow slides itwould havetobedoneintheafternoon.
Iapologize forthis. SomayIthengivethefloor toProfessor McLean.
Dr.McLean
3. Thank youMr.Chairman. Iwillbebriefandhighlight thepartsofmysubmission thatIthink
aremostgermane. Inrelation togoodpractice andgoodveterinary andgoodanimal husbandry practice,
Ithink itisimportant torealize thatthisgood practice isthepractice thatisnegotiated between the
sponsor oftheproduct andtheregistering authorities todefine theconditions under which thecompound
willbeused. Andoncethose conditions aredefined, thentheymake uppartoftheregistration approval
andinthatwaythemaximum residue limitcanbeestablished. Theother thing thatisimportant with
themaximum residue limitistounderstand thatitisalegallimitandnotahealth limit. Inother words,
theexceeding oftheMRL doesnotrepresent ahazard tohealth butisrather alimit atwhich the
authorities takeaction. However, Imust saythattoexceed theMRL would notbeseentobegood
practice. Inrelation tothemeat thatisproduced, toallintents andpurposes, themeat issimilar.
Infactitmaynotbepossible totellthedifference between meatproduced using growth-promoting
agents andmeatthatisproduced without them. Thatwhen welookatthose twohormones forwhich
there isamaximum residue limit, thenaminute residue mayremain thatcannot bedetected by
commonly-usedregulatorymethods.Ithinkitisimportanttorealizethatthemethodsusedareregulatory
methods rather thansome ofthemore sophisticated methods thatcangotoorders ofmagnitude below
theregulatory method. Ifwewererelying upon those sortsofmethods thenthesurveillance process
would becumbersome andcostly andactually preclude satisfactory surveillance. Oneofthekeysto
theuseofthesesortsofcompounds istocombine theuseofthecompounds withsurveillance toensure
thatgood practice isfollowed andtheMRL isnotexceeded.
4. JECFA haslooked atthese compounds particularly inits1988meeting andagain in1989and
itwasatthatpoint thattheADIandMRL wasestablished, orinthecases ofthree naturally-occurring
hormones itwasdeemed thatanMRL wasnotnecessary. These twomeetings were particularlyWT/DS48/R/CAN
Page261
important, because itwasdetermined forthethree naturally-occurring hormones thatthere wasno
wayofshowing thatmeat treated withthehormones oruntreated meat were substantially different
andsotherefore toregulate them byananalytical technique would notbepossible orpractical and
indeed inmany cases thelevels thatwereseenaftertreatment wereextremely small inrelation tothe
naturally-occurring substances. Itisinteresting tonotethatJECFA since1988and1989hasreviewed
anumber ofcompounds onasecond occasion. These compounds havebeenreferred totheJECFA
meetings bysponsors orbyregulatory authorities andgovernments. Butonnooccasion hasthematter
ofthedetermination the'88and'89JECFA meetings inrelation tothefivehormones thatitapproved
been,onnooccasionhasanyorganizationsoughttorevisitthematterofoestradiol17beta,progesterone,
testosterone, trenbolone andzeranol. Ithink itisveryimportant because onaverysignificant number
ofoccasions JECFA hasattherequest ofvarious groups revisited thematter ofthetoxicology and/or
theresidues ofproducts orcompounds thatitsetMRL andADIs for.Andthattheopportunity exists
andhasexisted since 1988 and1989 torevisit thematters ofthefivehormones under consideration
andthatopportunity hasnotbeentaken. Itisinteresting toseeatthisstage theamount ofmaterial
thatisalleged toshow thatthecompounds should berevisited, thatisbeing produced forthisparticular
meeting yetnoonehastaken theopportunity torefertoJECFA. Yetonnumber ofoccasions, asI
said, theopportunity todothatisbeing taken withother compounds. When JECFA approved the
useofthethree naturally-occurring hormones itaccepted thefactthatindeed welivevirtually ina
seaofhormones. These hormones came from endogenous levels produced inhumans, anditcame
inmaterial thatwetakeininthedieteither fromeating meatnaturally orfrom eating other material
thatcontains hormonally active substances; things thatarecommonly found inthedietincluding eggs,
soyaproducts, anumber ofplant materials andfungal products suchasthose from Fusarium from
which zeranol isderived. Indeed itisverydifficult todetermine exactly where ourhormone burden
comes frombutthefactsofthematter arethathumans areconstantly being exposed toverysignificant
levels ofhormones andthattheincidence oftumours associated which arewithhormones inhumans
suchas,forexample, thebreast ortheprostate, havenotsignificantly increased since thesurveying
hasbeencarried out.When Isaythatwemusttakeintoaccount thatthediagnostic technology available
fordiagnosing some ofthese tumours andalsothelevelofeducation ofthepublic hassubstantially
increased but,ifyoucorrect forthatsortofdataandcorrect itforage,thenthere hasbeenverylittle
change. Some ofthenewdatathathasbeensubmitted particularly relies upon invivoandinvitro
carcinogenicity testing andalsosome ofthemutagenicity testing butIdonotbelieve thatitisanymore
significant thanthesortofdatathatwasavailable atthetimetheoriginal appraisal wasmade.
5. Thehormones inquestion areusedinanumber ofcountries andhavebeenusedformany
years andepidemiological datadonotsuggest thatthishashadanuntoward effect onhuman health.
There areanumber ofcompounds thathavebeenusedinveterinary medicine orinassociation with
crops fromwhich wehaveseenuntoward effects inhumans, buttheresidues present inthefivehormones
inquestion havenotshown anydeleterious effects inhumans thathavebeenaccurately documented.
Many ofthehormones arelipidsoluble andtherefore passintothefatportion ofmilkandthatisa
significant intake forhumans, particularly foryoung children andalsoforadults intheintake ofbutter
andcheese; I'mreferring tothethree naturally-occurring hormones. Thehormones inquestion are
notwellabsorbed orally, andindeed theuptake there isextremely small withtheexception ofcourse
ofmelengestrol acetate. Aswell, there isdatathatshows thatanything uptoapproaching 80percent
ofsome ofthehormones areactually destroyed upon cooking.
6. Inrelation totheillegal cocktails, inthecountries where thecompounds areregistered then
theuseoftheillegal cocktails isvirtually non-existent. There areregistered products which are
combinations ofzeranol andtrenbolone, oestradiol andprogesterone ortrenbolone ortestosterone and
combinations likethatandtheregistration oftheproducts permits control ofuse. Inrelation tothe
useofthecompounds, theyarepackaged insuchawaythattheyareinaninertmatrix andthatmatrix
isinjected intotheanimal, intheear,byspecially developed injection apparatus, andthattherefore
doescontrol theinjection intotheanimal. Incountries where thedrugs arenotregistered andused
illegally thentheadministration byanacceptable technique thatcontrols therelease andisremoved
onslaughter, isnotavailable.WT/DS48/R/CAN
Page262
7. Coming backagain totheMRL, Istress thatitisalegal limitbased ondaily consumption
ofaproduct foralifetime corresponding totheuptake oftheADI, however, itisnotahealth limit
andoccasional consumption isofnoconcern andIthink Iwillstopthere Mr.Chairman.
Chairman
8. Thank youverymuch, Professor. Could yourstatement besummarized thatyoubelieve that
thecurrent standards wehavearefullyadequate toaddress theproblem?
Dr.McLean
9. Yes,Mr.Chairman, Idobelieve onhaving examined countries where thecompounds have
hadalonghistory ofuse,having examined thepackages ofdatasubmitted toJECFA andIthink it
isparticularly important thatpeople thataretalking about these hormones seethefullpackages ofdata
submitted toJECFA bythesponsors. These packages ofmaterial contain theindividual animal data
andaremuch more satisfactory ifoneisgoing topassjudgement thansome ofthematerial intheopen
literature. Where these compounds havebeenused, thenIbelieve thatevidence shows thattheyare
usedresponsibly ascompared withcountries where theuseisnotpermitted buttheyarestillused,
andunder those circumstances Ibelieve thatthereshould besome concern butusedinaccordance with
theagreed protocols, thenIbelieve thattheyaresafe.
Chairman
10. Thank youverymuch foryourstatement. Igivethefloor toDr.Arnold.
Dr.Arnold
11. Thank youMr.Chairman. Since Ishare many views expressed byProfessor McLean Iwill
notrepeat arguments putforward byhim. Iwillalsonottrytosummarize mywritten answers which
Ihavesubmitted induetime. Iwilltrytobeverybriefandonlymake afewverygeneral statements
atthistime.
12. Mygeneral viewoftheproblem isverysimilar towhathasbeenexpressed mostrecently by
theSteering Committee andaspecialist working party ofascientific conference ongrowth promotion
inmeatproduction organized bytheEuropean Community. Theexperts which hadbeeninvited by
Commissioner Fischler havesummarized, andthisisalsomyview, concerning thenatural sexhormones
andIreadfromtheirsummary: "Atpresent thereisnoevidence forpossible health riskstotheconsumer
duetotheuseofnatural sexhormones forgrowth promotion since residue levels ofthesubstances
measured inmeatoftreated animals fallwithin thephysiological range observed inmeatofcomparable
untreated animals. Thedailyproduction ofsexhormones byhumans ismuch higher thantheamounts
possiblyconsumedfrommeat.Eveninthemostsensitivehumans,pre-pubertalchildrenandmenopausal
women, duetoanextensive firstpassmetabolism, thebio-availability ofingested hormones islow,
thusproviding afurther safety margin." Andonzeranol andtrenbolone thisconference hasstated,
andIshare these views: "Atthedoses needed forgrowth promotion, residue levels arewellbelow
thelevels regarded assafe,theMRLs. There areatpresent noindications ofapossible human health
riskfrom thelowlevelofcovalently-bound residues oftrenbolone."
13. Thisismyfirstverygeneral statement. Concerning thenot-disputed carcinogenic properties
ofthese substances, mypersonal views verysimilar towhat hasmost recently beenexpressed by
Professor Jonathan Li,whoisaleading expert inthefieldofkidney carcinogenesis. Hehassummarized
onthebasisoftheevidence wehavetoday: "Theinescapable conclusion isthathormones, particularly
oestrogens, arenon-genotoxic carcinogens. Thislatter term, however, issomewhat misleading since
non-genotoxiccarcinogensbydefinitionultimatelyaffectpermanentgeneticchangesleadingtoneoplastic
transformation. Perhaps amore appropriate termwould beepigenotoxic, defined asreferring toanWT/DS48/R/CAN
Page263
agent thatisnotinvolved indirect covalent orindirect interactions withgenetic material, butnevertheless
isabletoelicit heritable changes byalternative mechanisms." Iaminclined toshare these views.
Ithink alotofconfusion hasemerged inrecent years because atthetimewhen thepolicies towards
genotoxic carcinogens have been established, genotoxicity hasmeant clear mutagenicity. Inthe
meantime, overthepastdecades, many testshavebeendeveloped which picked upveryearly end
points ofdamage tothegenome. Justtomention one,single-strand breaks, Icould mention many
others, intheDNA. Nowtheproblem is,itisclearly agenotoxic effect asingle-strand break observed,
forexample ,invitro.However thisPanel should know thattypically inacellthisevent occurs some
5,000 times perhourandthecapacity torepair suchadamage isintheorder of200,000 suchevents
perhour. Nowforexample, Igiveonlyoneexample, Dr.Liehr wasabletodemonstrate suchbreaks
atextremely highdoses andhewasabletodemonstrate atenpercentincrease itremains tobeconfirmed
thatsuchanevent isofanysignificance invivo. Ihavesimilar problems withDr.Metzler 'spaper
whoreports about genotoxic potential. Forexample, inhispaper onpage12,hesayswithrespect
toagents causing numerical chromosomal abberations (aneuploidy) abiochemical threshold canbe
expected ontheoretical grounds andcanbemeasured ininvitrosystems suchasculture cells. However,
itisimpossible todetermine thisthreshold inanintact organism invivo,because itisnotknown which
tissue ismost susceptible atwhich stage ofdevelopment andindifferent individuals. Forresidues
infood, exposure occurs forpeople ofallagesandvalues ofsusceptibilities. Iagree, firstofall,that
ontheoretical grounds thereshould beathreshold. Ialsoagree thatwedonotknow where thisthreshold
exactly liesbutwhatweperfectly know isthatthedoses which haveprovoked sucheffects aremany
ordersofmagnitudeabovetheconcentrationswearetalkingabouttoday,aminimumof1,000,sometimes
10,000 or100,000 times. There existmany papers andliterature which havedemonstrated thatthe
no-effect levels forsucheffects areintheorder ofonemicro-molar orslightly below andthere we
arestillfarabove theconcentrations wearetalking about today. So,myconclusion isalotofevidence
hasbeenputtogether about genotoxicity ofthesubstances, mostly invitro,buttherelevance tothe
invivosituation stillremains unclear. Particular activities havebeenfocused onthemetabolism of
theso-calledcatecholoestrogens.Thisisacategoryofcompoundswhichisknownsinceseveraldecades.
Ihadalready tolearn these structures when Iwasastudent andalsomore than20years agotheir
metabolic activation hasalready beenproposed. However, therealrelevant work hasbeendonein
thepastyears andtheideaisthatthesesubstances could beactivated inmetabolism toactascarcinogens.
Theproblem which Ihavewiththepapers written byDr.Liehr, notonlyontheoccasion ofthisPanel
butIhaveverycarefully examined, areview article hehaspublished lastyearinAnnual Review of
Pharmacology andToxicology, thatsometimes Ihavetheideathathedoesnotclearly discriminate
between whathasbeendoneaspurechemical synthesis orintestsininvitroandwhathasbeenshown
ininvivosituations. Icannot findanyevidence supporting theview thatthemetabolic pathways
elucidated tosometime byinvitro studies areofrelevance ininvivo. So,Ithink alotof
misunderstanding iscreated bythedifferent usesoftheterm"genotoxic carcinogen" asithasevolved
inhistory andasitisusednowadays. Ithink Iwould notliketoaddmuch more atthismoment, but
Iwillbeopentoanswer questions.
Chairman
14. Thank youverymuch Dr.Arnold. DoyouhavefromthePanel anyquestions atthemoment?
Notnow? Okay. Thank youverymuch foryourstatement. NowIgivethefloortoProfessor André,
please.
Dr.André
15. Thank you,Mr.Chairman. Iwillbeaveryshort forthemoment because Ididnotprepare
aspecific assessment. Youdon'taskbefore, butmaybe youdon'tknow howtomanage thismeeting
today.WT/DS48/R/CAN
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Chairman
16. Yes,andIdidn'taskyou,sothatthespeeches willbeshort indeed.
Dr.André
17. Okay, thank you. Soit'sanicesurprise. ButIthink alsothatmany things havebeensaid
before andwritten intheanswers tothequestions. Iwould justliketoaddsome comments, personal
comments. Asanexpert Iamhereasaveterinarian first,Iamabiochemist secondly. ButIamnow
working more intheanalytical fieldofresidue control ofthese hormones indispute. Andwhen I
received thequestions itlooked thatmany ofthese questions more orlessoutside myfieldofstrict
competence, because Iammore concerned withtoxicology aswellaswithsome veterinary oranimal
husbandry practices. However, Iaccept toanswer andIdecided atthebeginning towork asastudent
would do,which means looking atfirstatrecent scientific available dataandsynthesizing them. I
wasveryimpressed todiscover thenumber ofrecent publications, between 1990andnow,about these
topics ofhormones andspecifically onhormone 'saction inanimal health orabout theirtoxicology.
Ialsotryalways tostayoutside thepolitical debate andtobestrictly anhonest scientific. About some
points here, Ijustcomment. Forexample, about good animal husbandry practices aswellasgood
veterinary practices, ithasbeensaidjustbefore mytalkthatwhen drugs ingeneral areregistered,
thisregistration iswithsome withdrawal periods andrulesofimpairment. Infactproblems, thereal
problem, Ithink, istheproblem ofcontrol, howtobesurethatthese practices arereally respected
andwhatwecansaynowisthatofficial control services areincharge tocontrol these. Butalsothat
nowmore andmore people themselves, Iwould liketosay,people asveterinarians, asfarmers, as
farmer organizations, aretaking thecontrol andareensuring thattheywillonlyuseregistered drugs
asitispossible toofficially usethem. About residues andremaining residues, thereisaquestion about
thepersistence ofresidues inmeatandanimals. Itisclearthatthisdepends ofanydrugbutitsometimes
verysurprising todiscover thatwhen youdevelop newsophisticated methods, youobserve thatresidues
arestillremaining averyveryverylonger timethanitiscommonly known. Andwehavepersonal
experiences forcertain drugs, nearhormones inthisfield. About toxicity ofthese compounds, and
more precisely carcinogenicity orgenotoxicity, Iwasveryimpressed toreadmany papers about these
compounds, recent scientific papers (andIsentyoutheoriginal papers) andjustlooking faston
summaries, conclusions ofthesepapers, itseems foreverybody nowclearthattheyhaveverydramatic
toxicity andthatmost ofthenatural aswellassynthetic hormones haveanaction onDNA assaid
byDr.Arnold. Theproblem isjusttheproblem ofdoseresponse andtheproblem ofthreshold. I
think thatwhen acompound isusually recognized nowasgenotoxic, theproblem ofthreshold isnot
ofconcern. AndIwould liketocompare insimple words asif,Mr.Chairman, youwere student,
andIamsorry forthecomparison. Ifyoudrive, forexample, 30,000 miles ayear, youhave a
probability, arisk,tohaveanaccident. Ifyoudrive only1kilometre ayear,youhavealsoaprobability
tohaveanaccident. Youcannot saythatunder onethousand kilometres orunder athousand miles
ayear, youwillnever have anaccident. Andthatis,Ithink, thesame thing forthese kindof
compounds. Themore youuse,themore youhaverisktohaveanaccident. Butyouhavenolimit
under which itispossible tobesurethatyouwillnever haveanaccident. Sorry forthecomparison,
ifyouthink itistoosimple, butIthink itissometimes useful. Concerning theveryfirstproblem
ofJECFA andCodex andtheseinstitutions, itisclearthatthejobstheydoisveryuseful foreverybody
andthatnobody, noscientist, willthink thatitisabadassessment donebythese organizations. Ijust
haveapersonal problem about thedefinition ofdrugs aspublished bytheCodex, forthereason that
drugs inthese definitions involve allfamiliar known drugs butalsophysiological modifiers, asthese
hormones arewhen theyareusedforgrowth promotion. Andtomypersonal opinion, there isvery
bigdifference between adrug, Imean zootechnical andtherapeutical purposes ofthese hormones, and
theuseasgrowth promoter, forthereason thatyoumayadmit thatyouhaveasmall riskwhen use
adrugbecause inthiscase, youcannot avoid touseitanditisverymore difficult toadmit thatyou
takeariskwhen using justtomodify. Maybe alsotheconsequence isthatariskassessment forsuch
modifiers mustbedonewithother rulesthantheclassical rulesfordrugs. Thishasbeensaidinthe
previous conference inBrussels in1995. Coming backtothecomparison, youcanadmit thatyouWT/DS48/R/CAN
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could haveanaccident going tothehospital. Soforthemoment Ithink Iwillstopthespeech. I
apologize tooformyEnglish, which isbad, itisnotmymother tongue. Butwecanlatercome back
onmany points, ifyouwish.
Chairman
18. Thank youverymuch foryourexcellent introduction toyourpaper andassessment. MayI
nowturntoDr.Ritter.
Dr.Ritter
19. Thankyou,Mr.Chairman.Thiscommunicationsystem,Imustcomment,isawonderfuldevice
initselfforarbitration asitonlypermits oneperson tospeak atatime. Ishould saythatcoming fourth
following threedistinguished scientists leaves melittleopportunity toaddanything ofanyconsequence
additionally. Buthaving saidthatofcourse Iwilltaketheopportunity tosayafewthings. Ishould
begin byreally thanking thePanel fortheopportunity tocontribute tothedebate. Thisisadebate
which hasgoneonforsometime nowandIsuspect onewhich maycontinue forsometime yet,and
itisofcourse anextraordinary privilege tobegiven theopportunity tocontribute tothedebate with
myunderstanding oftheissue. So,Iamgrateful forthatunderstanding, forthatopportunity.
20. Iwillattempt toveryquickly addafewpoints tothose thathavealready beenmade bythose
whocame before me.Youknow ofcourse, Mr.Chairman, thatmyself andmythreecolleagues were
provided withaverylimited period oftimeinwhich toprovide comments andsoatleastinmycase
Ihaveattempted todosotothebestofmyability within thetimeconstraints thatwere provided.
There willbeunquestionably information thatsome maycitethatIomitted inmycomments andthat
isamatter, Ithink ofpractical necessity rather thananerror, ifyouwish. Informulating myopinions
Ihave, totheextent available tome,attempted touseaslarge aninternational database aspossible.
ThatiswhyIhavemade extensive useof...[data](?) [cassette sidefinished] ...byWHO, byJECFA,
byCodex andinthepublished scientific literature. Ihavenotreferred toproprietary data, evento
theextent towhich Imayhavehaditavailable tome.Ihave, ofcourse, made extensive reference
totheproceedings oftheEuropean Conference onGrowth Promotion fortworeasons. First and
foremost, because Ibelieve thatthatConference which washeldinBrussels inlate1995, represented
theviews ofanoutstanding group ofscientists from theinternational community andbrought some
considerable expertise tothedebate. Andsecondly, because Ibelieve thatthis1995-96 Conference
wasaveryimportant andveryrecent updating ofinformation which hadalready been reviewed
internationally byorganizations suchasJECFA in1988 andin1989. Socertainly itismyopinion
thatthiswhole issue hasbeenre-evaluated asrecently asearly 1996. Anditismyview thatthe
European Conference hasessentially reaffirmed, andindeed I'llgoasfarastosaystrengthened, the
earlier conclusions which were reached byJECFA, andthatisthatinaccordance withoperating
procedures thatareprovided fortheuseofthese substances, thattheirusedoesnotconstitute arisk
toconsumers offoodcommodities produced withthehormones atquestion, atleastforfiveofthe
six.ThePanel would beaware thatMGA hasnothadthebenefit ofaninternational review. My
colleague Professor McLean hasalready articulated thefactthatanMRL isnotahealth limit, butrather
aregulatory limit andthatthelimit maywellbedifferent indifferent jurisdictions fordifferent
operational reasons, because ofclimate, because ofgeography, because ofusepractice andotherwise.
ButtheADIisaninternational value. AndIwould draw theattention ofthePanel particularly tothe
pointthatforthethreenatural hormones, itwastheopinion ofJECFA, andindeed theviewre-enforced
bytheinternational conference inDecember of1995, thatthese natural hormones donotrequire the
establishment ofanacceptable daily intake, because infacttheirusereflects levels which areentirely
within therange thatonemight expect inanimals thathadnotbeentreated atall.Thatis,theiruse
would result inaresidue which would beindistinguishable fromanimals which hadnever beentreated.
Inthecaseofxenobiotic hormones itgoeswithout saying ofcourse thatthese hormones arenotnatural
bydefinition, andhence anylevelwhich canbedetected isoutside ofwhat onemight expect inan
animal which hasnothavebeentreated. Buteveninthatcase, theconclusion thathasbeendrawnWT/DS48/R/CAN
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internationally, isthatagain inaccordance withtherecommended useprocedures thattheselevels which
doremain constitute noriskwhatsoever forconsumers oftheproduct.
21. Ishould say,Mr.Chairman, thatthere hasbeensome considerable debate astothepotential
forabuse oftheseproducts andthehealth risksthatthisabuse mayconstitute. Iwould addmypersonal
conviction thatIdonotbelieve thatthepotential forabuse inanywayspeaks tothesafety ofappropriate
use.Imake thatpoint because thejuxtaposition thatiscreated often inthedebate isthatbecause there
ispotential forabuse ofanything, whether wearetalking about these hormones orwhether weare
talking about motor vehicles orwhether wearetalking about alcohol, Ithink weneedtoremember
thatthatpotential hasnoimpact whatsoever ontheappropriate use.Iwould alsosuggest tothePanel
thatbecause thepotential forabuse exists, inmyview, isnotareason toimpute thesafety ofappropriate
use.AndifImaybepermitted todrawaverysimplistic example, notunlike theonethatmycolleague
Professor André drew amoment ago,Ihardly think thatwewould beconsidering thebanning ofthe
automobile because some people speed. Itisaquestion ofriskmanagement andnotriskassessment.
Andtheissue thatIthink wehavetodealwithishowdowecontrol those people whospeed sothat
wecanallenjoythebenefitoftheautomobileandsimilarlyhowdoweappropriatelymanagethepotential
forabuse withthese hormones rather thanimply thatthisabuse somehow oranother makes the
appropriate useunsafe. Ishould addperhaps before Ileave theissue ofabuse justveryquickly that
itisnoteworthy thatincountries where useofthese hormones, thesixhormones inparticular, has
been permitted foraveryextended period oftime, andIrefer most notably toCanada andthe
United States, monitoring andcompliance programmes which havebeenongoing nowfrommany many
years haveconsistently demonstrated thatresidue levels areentirely within recommended limits and
thatinstances ofviolative residues, thatisresidues which would indicate abuses taking place, have
almost never beenreported. Sothatitseems thatatleastinthose jurisdictions where useislawful,
thepracticality ofabuse hasnever become areality. There are,asIsay,fewandisolated examples
ofviolative residues inthose countries where usehasinfactbeenpermitted.
22. Itisperhaps important, Ithink, tobring totheattention ofthePanel thefactthatwehavean
enormously richexperience inthehuman casewiththese hormones, andIdraw thePanel'sattention
specifically totheuseofoestrogen, andmost notably oestrogen incombination withprogesterone,
asanoralcontraceptive which hasnowbeeninpractice inthehuman population forperhaps 35to
40years andthatthere havebeentensofmillions ifnothundreds ofmillions ofwomen whohave
taken these steroids onadaily basis, inmany instances fortheirentire reproductive life,periods of
timethatmayhaveranged from30to50years. Andthattheselevels havetypically reflected anintake
andexposure thatranges somewhere between 20and100micrograms, depending onthepharmaceutical
preparation, onadaily basis fortheentire reproductive cycle ofthehundreds ofmillions ofwomen
inquestion. Itisinteresting tonotethatthese levels arethousands, ifnothundreds ofthousands, of
times greater thanthelevels, Mr.Chairman, towhich youorImight beexposed inconsuming meat
which results fromtheuseofthese hormones inproduction. Andalthough theissueofbreast cancer
mostnotably iscertainly oneofconsiderable interest these days, Ithink itisfairtosaythattodate,
thereisnocompelling evidence whatsoever todemonstrate thattheuseoforalcontraceptives containing
twooftheveryhormones atissue before thispanel, overatleastanentire generation inhundreds of
millions ofpatients, hasnotresulted inanycompelling evidence tosuggest thattheuseofthese drugs
infactconstitutes anyincreased risktothese women ofcancer whatsoever. Finally, Mr.Chairman,
Iwould onlyconclude bysaying thatcertainly inthecaseofthenatural hormones, andasIhavealready
indicated atleastinthecaseoftrenbolone andzeranol forthexenobiotic hormones, Ithink thefive
haveallbeensubjected tobothnational andinternational reviews which havebeenre-reviewed, ifyou
like,asrecently asDecember 1995. Itwould certainly bemyview, Iwould certainly share theviews
expressed bothbyJECFA andbythisinternational forum thattheuseofthesecompounds, inaccordance
withprovisions provided onaregulatory levelfortheiruseincountries thatinfactpermit theuseof
these products, doesnotconstitute anincreased riskorharm tothose consumers whoconsume food
commodities produced withtheaidofthese hormones. Thank you,Mr.Chairman.WT/DS48/R/CAN
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Chairman
23. Thank youverymuch foryourstatement. MayIturnnowtoDr.Lucier.
Dr.Lucier
24. Thank you,Mr.Chairman andIalsothank thePanel forinviting metoparticipate inthisreview.
Mycomments really evolve from myresearch activities inthefieldofreceptor biology. Ihavehad
alaboratory activity intheareaofreceptor biology forover20years now, andmore recently Ihave
beeninvolved incoordinating anational toxicology programme within theDepartment ofHealth and
Human Services oftheUnited States, thatisresponsible forproviding atoxicological evaluation on
agents ofpublic health concerned whether theybeintheenvironment, intheworkplace, infoodstuffs,
physical agents andsoforth. Ihavealsobeeninvolved overtheyears working withtheInternational
Agency onResearch onCancer onanumber oftheirefforts intheirhazard identification, theirrisk
identification, chemical carcinogens andinparticular those inwhich hormonal activity seems tobe
attherootofthepotential carcinogenic activity. Having come last,Iprobably won'tsaytoomany
things thathaven 'tbeensaidbefore, butletmegothrough some ofthekeyissues atleastfrom my
perspective andthose thatIfeelcomfortable incommenting on.Oneisthattheresidues thatoccur
from thenatural hormones arecertainly going tobeindistinguishable from those which occur from
thenatural endogenous materials. Thisisnottrue,ofcourse, forthesynthetics. With appropriate
analytical methods andappropriate residue levels oneiscapable ofdetecting residues ofthesynthetic
materials hereinquestion. Ishould alsopoint outthatthehalf-life, thebiological persistence, ofthe
agents inquestion isforthemost partrather short. They donotstickaround thebody verylong.
Buthaving saidthat,halflifebeing justwhatitsaysisthetimeinwhich ittakes forhalfthematerial
todisappear. So,ifsomething hasahalflifeofonedayifyoustartoutwithtenunitsofit,oneday
lateryouhavefive,twodayslateryouhavetwoandahalfandsoforth. Soeventhough several months
mayelapse following anexposure toanagent evenwitharelatively short halflife,afewmolecules
mayremain. Thenumber ofmolecules mayberemarkably close tozero, probably notdetectable by
analytical methods, butafewmolecules willlikely remain. Ishould alsopoint outinterms ofthe
carcinogenic activity ofthehormones inquestion, wealready know thatphysiological levels,
naturally-occurring levels ofandrogens andoestrogens arecarcinogenic. Oneoutoftenwomen in
theindustrialized world getsbreast cancer. There iscompelling mechanistic biological information,
human studies andtoxicological studies toshow thatoestrogens areattherootofthis.Thattheircancer
isamulti-step process butthatoestrogens appear toberesponsible forthemajority ofthecarcinogens
thatareseeninthesite. Sowealready know thatphysiological levels arecarcinogenic. Wealready
know thatearlymenarche increases risk,latemenopause increases risk. Weknow thatwhen awoman
loses herovaries andheroestrogen production diminishes, therisktobreast cancer alsodiminishes.
Charles Huggins inhisnoteworthy work backintheearly sixties show thatovariectomy (removal of
theovaries) prevented breast cancer inexperimental animals. Thesame istrueofendometrial cancer.
Weknow fromhuman studies thatendometrial cancer iselevated significantly byexposure tooestrogen
replacement therapy when thisisunopposed byprogesterone. Conjugated oestrogens havebeencalled
aknown human carcinogen bytheInternational Agency forResearch onCancer. DESofcourse has,
butDESisnotaquestion hereandthemechanism bywhich DESproduces cancer maynotberelevant
totheissues here. Tamoxifen, ananti-oestrogen inbreasts, produces cancer intheendometrium because
itactslikeanoestrogen intheendometrium, theuterus. Itactslikeananti-oestrogen inthebreast
soitblocks ...chemotherapeutic agent inwomen whohavebreast cancer andthesizeofthetumours
frequently diminish afterthisexposure. Oralcontraceptives arealsoaknown human carcinogen but
notbecause ofbreast cancer. They areaknown human carcinogen because ofincreased riskofliver
cancer. Theincreased riskisquitesmall, butnevertheless therehasbeenaconsistent riskshown across
studies. After having saidthat,Ineedtoaddthatthenumber ofmolecules thatremain following
appropriate useofthese agents isverysmall. They areverysmall inrelation totheamount of
naturally-occurring oestrogens orandrogens. Sotheaccompanying riskthatwould beassociated by
consuming meatcontaining residues would beextraordinarily small. Itwould beveryhardonscientific
grounds tosaythattheriskwaszero. Butitislikely tobevery, verysmall. Itcould bezero. ItWT/DS48/R/CAN
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could beashighasbyestimates asonecancer inamillion people exposed tothemovertheirlifetime.
Sotherisk,tosumupthose comments, issomewhere between zeroandsomewhere around onein
amillion. Andthatoneinamillion isaverydifficult number topindown. Alotofassumptions
gointoit.What Iwould saywould beaconservative estimate, anupper bound estimate, andIcan
gothrough astohowIcame upwiththatnumber ifthose details arerequired. Acouple ofother points
thatIwould likemake. Oneisthattheissue ofthreshold really isnotrelevant here. AsIalready
said,theamount ofmaterial thatisadded totheexisting burden isveryverysmall. Theamount of
naturally-occurring oestrogens andlikely androgens arealready carcinogenic, soyouarealready adding
toacarcinogenic burden. Sotheissueofthreshold istotally irrelevant tothetoxicological evaluation
ofthese agents. Itmayalsobeirrelevant todistinguish between genotoxic andgenotoxicity, when
onegetsrightdown toit.Iwould saythatthere isagreat dealofevidence tosupport thenotion that
receptor mediated events, i.e.normal hormone pathways, arethemain reason whyhormones and
hormonal agents arecarcinogenic. However, there isabodyofknowledge thatsuggests thattheydo
genotoxic activity, thisgenotoxic activity could possibly contribute tothecarcinogenicity Imean there
areexamples ofsome invivoexperiments thathaveshown thisinwhole animals, andIcangoover
thoseifrequested. Butmybottom lineisanextensive discussion ofgenotoxicity versus non-genotoxicity
really isn'trelevant tothediscussion andtotheoutcome because wealready know thattheexisting
levels ofhormone arecarcinogenic. Theonlyreason fordistinguishing genotoxicity from non-
genotoxicity inmyunderstanding, anditmaybeanaive understanding, istodetermine whether or
nottoapply alinear orathreshold model forriskassessment. Athreshold model would assume that
there isadosebelow which noeffect could occur. Since wearealready intotheeffect region, again
weareadding anexisting burden byadding anexisting number ofchemicals tothatburden, again
keeping inmind thatthisisaverysmall addition andmayberemarkably close tozero. Wealso,in
thecourse ofthenational toxicology programme, donecarcinogenicity evaluations onapproximately
500agents. Many ofthese agents arecarcinogenic byvirtue oftheirgenotoxic activity, many are
carcinogenic byvirtue oftheirnon-genotoxic activity. When welooked atthose response relationships
forgenotoxic andnon-genotoxic carcinogens, wecouldn 'tdistinguish onefrom theother. Inother
words, non-genotoxic carcinogens werenomore likely toexhibit linear behaviour thangenotoxic ones.
Soagain thatgoesbacktomypoint thatthegenotoxic versus non-genotoxic issue, Idon'tthink that
isarealone. Acouple ofother points tomake. Oneis,when onelooks atthenatural versus the
synthetic compounds, thesynthetic compounds clearly havehormonal activities, that'swhytheyare
usedinthesituation. They mayalsohaveother kinds ofactivity inaddition tothatbecause molecular
structureisdifferentthanthatforthenaturally-occurringoestrogenssotheremaybedifferentmetabolites,
possibly adifferent spectrum ofadverse effects. Iassume thatwhen onelooks atthetoxicological
datathatisavailable onthese, andnotallofitwasavailable tomebecause some ofitisproprietary,
thattheappropriate studies would bedonetodetermine thatother effects arenotoccurring. Effects
thatcould bedetected bysub-chronic 90daysstudies orthreeyearstudies andbyappropriate molecular
screening techniques. Another point regarding thecocktails, thesynergy. There wasarecent paper
indicating possible synergy ofoestrogens inscience, using yeast. Atthispoint, therelevance ofthat
system toevenriskhasnotbeenshown, andthose results havenotbeenrepeated inhuman cells.
SoIthinktheissueofsynergy, more thanyoumight expect fromadding twoweak oestrogens together,
theissue ofadditivity orantagonism, ofoneinhibiting theother, really isanopenquestion. Inmy
mind, additivity istheappropriate waytoestablish risk. Ishould alsoreiterate again thatcancer is
amulti-step process. Wecandefine thedifferent steps operationally, insome cases, somewhat
mechanistically. Itinvolves DNA damaging steps, creation ofmutation, theability ofcellsthatharbour
thismutation toproliferate more rapidly thannormal cells. Itisgenerally thought thatoestrogens act
primarily atthatstepthatstimulates thegrowth rateofgenetically altered cells, cellsthatalready harbour
mutation, andthere isawealth ofscientific information andliterature toshow that. Thework by
Dr.Liehr, Dr.Metzler, Dr.Cavalieri andotherfolksindicate thattheremaybesome genotoxic activity
forthese agents, suggesting thattheymayacttosome extent onthatfirststep, which would bethe
creation ofthatmutation. Soitappears possible thatwithin theframework ofamulti-step model for
cancer, thathormones andthese hormones inquestion byactonmore thanonestep. Andthelast
point thatIwanttomake iswetalkalotabout thetoxicology ofthese agents, however, itisimportant
topoint outthatoestrogens havebeenusedintherapy foralongtimeformany purposes. CertainlyWT/DS48/R/CAN
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oestrogen replacement therapy isone.There isaconvincing bodyofknowledge toshow thatoestrogens
canprevent bonelossinwomen whoaresusceptible tothat,soitcanreduce theriskofosteoporosis.
There arealsostudies toshow thatoestrogens candecrease heart disease. Sowhen onestarts looking
atanoverall riskassessment, thesmall amount ofoestrogens thatareadded bytheconsumption of
meatcontaining these residues, itseems appropriate alsotolookatthewhole balance ofeffects, what
arethebenefits versus risks. AndIthink thatisgoing tobeahardquestion toanswer. There may
beaveryverysmall riskfromadding these smaller molecules ,butthere mayalsobeasmall benefit.
Idon'tthink wehavethetools inwhich toadequately determine thatriskbenefit ratio, andIthink
thatisgoing tobeoneofthedifficulties thatthePanel hasincoming togrips with what
recommendations, whatdecision thattheymake. Letmestopthere, andagain Iwillbegladtoadd
more details tomycomments orrespond toquestions asthemeeting ison.
Chairman
25. Thank youverymuch foryourintroduction. MayIgivethefloortoDr.Randell, theCodex
expert.
Dr.Randell (Codex)
26. Thank you,Mr.Chairman. Andthank youfortheopportunity ofmeeting withyouandyour
fellow Panel members. Andalsofortheopportunity ofmeeting somany oldcolleagues frommyJECFA
days; Ihaven 'tseensome ofthemforquiteanumber ofyears. JECFA istheFAO-WHO JointExpert
Committee onFood Additives. Itwasfounded in1955byFAOandWHO withtheintention ofgiving
guidance tothese organizations andtheirmember governments onthematter ofchemical substances
added tofood, essentially forwhatever reason. Initsearlydays, JECFA established whatwasknown
astheADI(Acceptable Daily Intake) concept, initiated infactbyProfessor Rene Truhaut, whoisno
longer withus.TheADIconcept isbuiltaround aconcept ofadding noappreciable riskwhen you
addchemicals tofood. Thatconcept hasbeenwithus,asIsay,since thelate1950s andwithvery
minor modifications itstands asitstands today. Chemicals thathavebeengiven anADIbyJECFA,
orbynational authorities because thesame concept hasbeenadopted bymany national authorities,
anintake lessthanthatADI, overalifetime, produce noappreciable risktotheperson consuming
it.In1960-61, FAO andWHO thenturned theirattention topesticide residues andthejointmeetings
onpesticide residues formulated theconcept oftheMaximum Residue Level. Thisisdifferent tothe
ADI. Maximum Residue Limit wasestablished toensure thatpesticides usedinfieldconditions under
goodagricultural practice didwhattheyweresupposed todoanddiditwithin aframework ofsafety.
IfIcould usearelatively simple explanation oftheMRL inthepesticide context. Ifweapply apesticide
toafieldwedoitforcertain reasons, wedoittokillapest. Ifyouapply more thanthatthenyou
haveexceeded whatyouneedtodoandyouhavesurplus residue, which isthought tobeanunwise
thing. Ifyouspray lesspesticide onthefieldyougettheworst ofbothworlds: yougetthepestand
yougetresidues which youdidn'twanttohaveinthefirstplace. Sotoacertain extent themaximum
residue levelisameasure ofhowmuch ofthechemical isneeded toachieve theobjective ofpestcontrol
andatthesame timefallswithin theframework ofthesafety analysis. JECFA andJMPR wereexpert
committees andtheystillareexpert committees. Anditwasin1962thatFAO andWHO formed the
intergovernmental Codex Alimentarius Commission, which wasestablished toprotect thehealth of
consumers andtofacilitate, toremove unnecessary barriers totrade infoodproducts. Thework of
Codex, thework ofJECFA andthework ofJMPR wenton,andstillgoeson,withincreased interest
from many parties andcertainly alotofincreased interest since theMarrakesh Agreement. Inthe
early1980s, anumber ofCodex committees began toraisequestions, governments atthese committee
meetings, began toraisequestions about howdowedealwiththeresidues ofthesubstances usedfor
growth promotion. Itisofinterest tonotethatthese were brought upinthePesticide Residues
Committee,CommitteeonFoodAdditives,CommitteeonMeatHygiene,CommitteeonPoultryProducts.
There wasinfactsome sortofcompetition between theCodex committees astowhowasgoing to
handle thishotpotato. In1984, FAO andWHO convened anexpert consultation toadvise thetwo
organizations onhowtohandle thisparticular problem. Itwasanexpert consultation onprocess ratherWT/DS48/R/CAN
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thanonscientific detail. However, theconsultation didcome totheconclusion thatitwasanappropriate
areaforCodex towork in;thatthemost significant problem inthefieldwasnotthelegitimate use
ofgrowth promoters oranyother veterinary drugs, under good veterinary practice conditions, but
rather theabuse oruncontrolled use;thatitwould beappropriate fortheCodex Commission toestablish
aseparate committee tohandle these matters. Andtheexpert consultation alsohadthefirststabat
providing adefinition ofwhatwasmeant byveterinary drugs. Itwastheintention oftheexperts of
thisconsultation, andIwasprivileged tobethesecretary ofthatconsultation, tomake thedefinition
asbroad asonecould possibly imagine andthisiswhyweevengetreferences inthedefinition to
apiculture andbeegrowing. Theexpert consultation resulted intheestablishment ofacommittee by
theCodex Alimentarius forresidues ofveterinary drugs infood, anditalsogavethestimulus forJECFA
tobegin work inthisareainearnest andtoobtain thefirstreally comprehensive datapackages onthe
substances about which wearespeaking today. Theywereevaluated in1987, andafollow-up evaluation
fortrenbolone acetate in1989. Therecommendations oftheJECFA wereintheform ofmaximum
residue limits (MRLs) although ofcourse fortheendogenous hormones therather peculiar statement
thattheMRL wasthatanMRL notnecessary, aninternal tautology which Ithink wearegoing to
havetolivewithforsometime. These MRLs were processed through theCodex system andwere
firstdiscussed atthe19thCodex Alimentarius Commission session in1991, when itwasdecided not
toadopt theMRLs astheycurrently stood. When thecomplementary information ontrenbolone acetate
hadpassed through thesystem, theMRLs werere-presented foradoption at21stsession oftheCodex
Alimentarius Commission, andwere adopted. Thatisthehistorical level.
27. Onthescientific side,Iwould liketocome backtoquestions which youasked theCodex and
Iassume JECFA Secretariat inyourwritten questions, particularly about therelationship between the
acceptable daily intake andthemaximum residue limitandwhether ornotthese aremeasures ofthe
acceptable risk.Themaximum residue limitisdefinitely notahealth-based limit. Itisalimitestablished
forthecontrol ofveterinary drugs inactual practice. Thethinking which goesintotheestablishment
ofamaximum residue limitissuchthatthemaximum residue limitwillnever leadtoresidues which
would, inanormal ingestion oftheproduct, cause anyconsumer toexceed theacceptable dailyintake.
Thereforethereisanupperboundarytothemaximumresiduelimitimposedbytoxicologyconsiderations.
Thelower limitisnormally derived from residue trials inpractice according totheproposed good
veterinary practices intheuseofthese drugs. However, incertainly onecase, inthecaseofzeranol,
thislimitfallssofarbelow notonlythetoxicologically derived limitbutitevenfallswellbelow the
limit thatonecandetermine withnormal methods ofanalytical chemistry, andtherefore hasbeen
increased totakeintoaccount thefactthatifyouaregoing tooperate adecent control programme,
thatisnotgoing tobeoverly expensive, thanyouhavealimitwhich iscontrolled bytheanalytical
procedure rather thanbytheresidue trials. Theacceptable daily intake itself alsoisnotadirect risk
assessment inthesense thatitprovides astatement ofquantitative risk. TheADIconcept states that
there willbenoappreciable riskasaresult ofexposure tothechemicals concerned. Thisistrueof
within theJECFA andJMPR framework. Thisistrueoffoodadditives, residues ofveterinary drugs
andpesticide residues. Iappreciate verymuch yourcomment Dr.Lucier thattheriskisprobably
somewhere between zeroandoneinamillion (oneintentotheminus six),because thisdoesputsome
sortofquantitative framework onthat. ButJECFA hasnever established aquantitative evaluation
ofriskintheapplication oftheADI. Ithink Iwillleave myintroductory comments there ifthatis
satisfactory toyou,butIwould beverypleased toanswer additional questions ontheevaluations.
Thank you.
Chairman
28. Thank youverymuch, Mr.Randell. According toourprocedures, Iwould nowliketogive
thefloor totheUnited States delegation forcomments orquestions totheexperts. MayIgiveyou
thefloor, Mr.Brinza?WT/DS48/R/CAN
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Mr.Brinza (US)
29. Thank you,Mr.Chairman. Firstwithrespect tocomments ontheresponses thatwereceived
from theexperts, wedohavesome written comments thatwewould liketomake available toyou
allnowthatwould facilitate usgetting through whatIsuspect would bealengthy exercise -itwould
notbeveryfruitful tojustreadthem. Soletmeprovide those toyou. Ithink weshould haveenough
copies forthePanel andtheexperts aswellasfortheother delegations. Wethought itwould beuseful
toasksome questions thatwould gotoallfiveoftheexperts. Therepresentative fromCodex ofcourse
iswelcome torespond aswell, butweassume thatyouareserving more inyourex-officio capacity
withrespect totheCodex institutional issues. What wewould liketodowould betoasksome questions
ofallfive,thatIthink would befairly simple questions, justtomake surethatweunderstood theareas
oftheresponses where there wasconsensus since there weredifferent responses -there wereinsome
cases different wordings -sowejustwanttomake sureweunderstood correctly alltheresponses and
thefoundations forsome ofthose responses.
30. Forexample, withrespect tothethree natural hormones -oestradiol 17beta, progesterone
andtestosterone -weassumed thatallfivewould agree thatthese three compounds areallpresent in
themeat-producing animals aswellasinhumans naturally (endogenously produced, Ithink, would
bethebetter wayofexplaining that).
31. Secondly, assuming thatistrue,dotheyalsoagree thatthese three hormones areallnaturally
present inthemeatandthemilkfrom those animals? Ibelieve wehaveheard some oftheexperts
already refer tothatbutitcould beuseful tomake surethatallthefiveofthem agree withthat.
Assumingthereisagreementonthat,whenfoodproductscontainingthenaturallevelsofthesehormones,
inother words levels within thenormal physiological range, dothesehormones haveabiological effect
onconsumers? Wehaveafewmore likethisandIwilldefer toyouonwhether itisappropriate to
getresponses nowonthose andthenwegoonfromthereorwhether youprefer todothemallatonce
inthisparticular series andthenhavetheresponses. Itmaybedifficult forthem tokeeptrack ofthe
different questions.
Chairman
32. Iwould propose thatyoudirectly putthequestions tothePanel andenter intoadialogue and
thengoonthrough yourprogramme.
Mr.Brinza (US)
33. Thank you,Mr.Chairman. Ifthatistheinstance then, ifIcould askthefiveexperts with
respect toeachofthose firstthree questions, Ijustwanttomake sureweunderstood correctly your
responses, firstly arethese three hormones naturally present inthemeat-producing animals andin
humans? Itmaybeuseful tojustgoaround thetablestarting withDr.Ritter.
Dr.Ritter
34. Theextent towhich theyarepresented ofcourse asyouwillknow isafunction tosome extent
ofthestatus ofthehuman inquestion andtheage,buttoprovide ageneral answer, Ithink, inmy
viewthegeneral answer is"yes", noting thatthere willbesome exceptions invariance onthedegree.
Iunderstand thatthelevels aredifferent butthattheyareallpresent tosome extent.
Dr.McLean
35. Yes. There willbevariations inlevels butthethree naturally-occurring hormones arefound
inbothanimals andhumans.WT/DS48/R/CAN
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Dr.Arnold
36. Iagree, Mr.Chairman, andweperfectly know thelevels occurring fromfetallifetountilvery
lateage.
Dr.André
37. Yes. Thehormones arethesame butitisnotclear ifthemetabolites sometimes could be
different. Forexample, ifyougiveanatural hormone as(.?.)tocalves ortoanymeat producing
animals, theycanmetabolize andtransform thehormone andinthese conditions thefoodintake for
human isnotthesame. Youseeanimals havebeentreated asiftheyarenottreated, qualitatively.
Dr.Arnold
38. IfIcould justclarify withProfessor André, arewetalking about levels ofthatmagnitude with
respect totheadministration ofanyofthese three forgrowth promotion purposes inaccordance with
good animal husbandry practice?
Dr.André
39. Themetabolic transformation, thebiological transformation, istotally independent ofthelevel.
Itisnotaproblem oflevel. Maybe Idon'tunderstand wellyourquestion.
Dr.Arnold
40. Ithought yourearlier answer hadbeenthatthereisapossibility thatthesecould beadministered
atsuchalevelthattheycannot bemetabolized bytheanimal. Andmyquestion was,arethedoses
wearetalking about forgrowth promotion sohighthattheywould beatalevelthattheanimal cannot
metabolize them.
Chairman
41. There willbenoanswer tothis.
Dr.Lucier
42. Yes,these materials would bepresent atallstages oflife,inbothmales andfemales, asmy
colleagues havesaid,invarying amounts.
Mr.Brinza (US)
43. Then, thenextquestion was,would thehormones alsobepresent inthemeatoftheanimals
andmilkfrom those animals? Again recognizing thatthelevels willvary.
Dr.Arnold
44. Mr.Chairman, Ithink there aredifferent pathways ofmetabolism forthese substances. And
certainly athighlevels, itdepends somewhat onthedosewhich pathway isused, butessentially
metabolism issimilar inanimal andinman. Forexample, incattle the17alpha oestradiol plays a
certain greater rolethaninhuman beings, butthismetabolite islessactive asanoestrogen orpractically
notactive asanoestrogen. Sothere areslight differences.WT/DS48/R/CAN
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Chairman
45. Thisgoestothefirstquestion. IamverygladIcould understand this.Solet'sgotothesecond
question, then. Justasamatter ofprocedure, wedon'tgoforconsensus. Wejusttakeandrecord
whattheexperts say,butwearenottrying toassess some consensus here.
Mr.Brinza (US)
46. Iunderstand, Mr.Chairman. Itisjustthattotheextent thatwearealltalking fromacommon
understanding ofthefacts, thenitisuseful forustoperceive that. Yes,thesecond question isthen
willeachofthesethreehormones bepresent inthemeatandthemilkfromtheseanimals -theoestradiol
17beta, testosterone andprogesterone.
Dr.Ritter
47. Subject tothesame variances thatIindicated amoment ago,theanswer isyes.
Chairman
48. They willbeinthemilk?
Dr.Ritter
49. Yes,again subject tothesame variances thatwediscussed amoment ago,although thelevels
andtheextent towhich theyarepresent andtheratios andsoonandsoforth willbeafunction of
theparticular status oftheanimal inquestion, buttoavoid going intoalengthier response, thanis
really necessary inthegeneral casetheanswer Mr.Chairman, Ithink would beyes.They would be
present.
Mr.Brinza (US)
50. Mr.Chairman, itmaybeuseful aspartofthese questions, tosavesome time, wearealso
asking whether thelevels thatwearetalking about would bewithin thenormal physiological range
withrespect tothese hormones when theyareadministered forgrowth promotion purposes.
Dr.Ritter
51. Toanswer thatquestion, again theanswer isyes.Theposition, certainly thatthethatIhave
offered, Mr.Chairman, isatleastthatwhen thesesubstances areusedinaccordance withtheprescribed
useconditions, thelevels thatarepresent areinfactindistinguishable fromthosewhich would bepresent
inananimal which hadnotbeentreated atall.Ishould say,toclarify thatjustalittlebitfurther,
there isarange ofconcentrations which iswhat Ihavebeenattempting toallude tothatonemight
normally detect inuntreated animals. It'snotafinite number, butrather thereisadistribution ofvalues
overwhich onetypically might findthese hormones inanuntreated animal. Thelevels inanimals
thathavebeentreated fallswithin therange ofthose numbers thatmight bedetected inanimals that
haveotherwise [cassette ended ...]
52. Idon'twanttoimpart theimpression thatthere isaprecise number fortestosterone levels,
there isarange ofvalues thatonefinds. Asonemight expect, these arebiological living systems
andthereisadistribution ofvalues, buttreatment results inaresidue levelwhich fallswithin thatrange.WT/DS48/R/CAN
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Dr.McLean
53. Mr.Chairman, theanswer isyesandtofacilitate anexplanation, Isuggest thatifyoulook
atAttachment 1ofmysubmission, thenthereareanumber offigures intherethatrelate toprogesterone
tooestradiol 17beta,andtotestosterone invarious tissues andinparticular theexcretion inthemilk,
andwhen youcome totheother thannaturally-occurring hormones, fortheother hormones trenbolone
andzeranol, because theyarelipidsoluble, onewould expect themtoappear inthetissues andinthe
milk.
Dr.Arnold
54. Chairman, wehavearather complete databaseshowing us,astheprevious speakers have
already said,there isalarge variability according tophysiological status andthere canbeafactor for
certain hormones upto1,000 andIhavepresented thedatainmywritten responses. Therefore Iagree
thatifthesubstances areusedaccording togood veterinary practices, either forgrowth, promotion
orforthetherapeutic usesauthorized intheEC,youhaveinitially aslight difference butatthetime
ofslaughter there isnomeans todiscriminate between treated andnon-treated animals, irrespective
ofwhether forgrowth promotion orfortherapeutic andzootechnical purposes.
Dr.André
55. Yes,bothhormones arepresent inmeatandmilk, it'sclear, andthelevelisaveryvariable
levelisclearalso. Idon'tagree withProfessor Arnold justonthelastpoint, when hesaysthatitis
impossible todistinguish between hormones, injected hormones andnatural produced hormones. In
some cases itispossible todistinguish thetwobyphysical means ofisotope relations, butmaybe not
ataverylowlevels, itisverydifficult todo.
Chairman
56. Thank you.
Dr.Lucier
57. Yes,these materials arepresent inmilkatvarying levels. Progesterone ismuch higher than
theother two,asmuch asa100to1,000 times higher, buttheyallarepresent.
Chairman
58. Thank you. Youwanted toreply.
Dr.Arnold
59. Abroad comment onProfessor André, Itotally agree thisisatheoretical possibility, ifyou
labelthehormones withstable isotopes, youcandiscriminate between added hormones andendogenous
hormones, butthishasabsolutely norelevance inpractice.
Dr.André
60. No,Itotally disagree. Iwasspeaking about natural occurring isotopes, C-12, C-13 andits
possible todistinguish inthiscase, some hormones naturally-occurring orinjected, astheydoin
sportsmen. They dothiscurrently insportsmen nowfordoping insport andtheycandistinguish
endogenous testosterone andinjected testosterone, evenifthecompound isreally thesame, butthe
isotopic composition isnotreally thesame.WT/DS48/R/CAN
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Chairman
61. Thank you,Sir.Wetakenoteofthetwoviews.
Dr.McLean
62. Ijustwanttoaddanother thing. Ithink itisimportant when onelooks atmilk, thatbecause
these hormones arefatsoluble, thentheconcentration inthetwocommonly usedorcommon articles
ofcommerce, which arecream andmilk, isverysubstantially greater. Itissomething oftheorder
ofthree tofourtimes intocream andabout 40times intobutter, andsoIthink onemusttakethatinto
account aswell.
Chairman
63. Thank you. Then thenextquestion wasatthelevels wearetalking about, within thenormal
physiological range, would these residue hormones haveabiological effect ontheconsumer?
Dr.Ritter
64. Ithink thattoattempt toanswer thatquestion would really betopre-empt theoutcome ofthis
Panel. Ithink thatisthequestion which thePanel willendeavour toanswer. SoMr.Chairman, with
respect, Ithink theissuethatyoufaceattheendoftheseproceedings istoanswer exactly thatquestion.
Atthelevels thatarepresent aftertheuse,doesthisconstitute alevelwhich mayresult inabiological
activity? Iamgoing to,ifImayMr.Chairman, modify yourquestion alittlebittotheoneIwould
liketoanswer, rather thantheoneyouasked. ImustsayIfeelsomewhat restrained tomake anattempt
toanswer yourquestion directly forthereasons thatIhavesaid. Because asIhaveindicated, atleast
inmyview, thatinthecaseofthenatural hormones these levels thatarepresent inthemeatoftreated
animals isessentially within therange thatitwould bepresent inthemeatofuntreated animals, Iwould
suggest thatthequestion becomes moot astowhether ornotthereisbiological activity associated with
these levels ofthehormone. Ithink itisamoot point because thelevelisnogreater orlesser than
itwould beinthemeat ofanuntreated animal. Thatisaconsumer would beexposed tonolesser
orgreater biological activity asaresult ofthislevelfromeither atreated animal orfromanuntreated
animal because bothlevels areessentially inthesame range. Thank you.
Dr.McLean
65. Mr.Chairman, inrelation tothenaturally-occurring hormones, thenitisnotpossible to
differentiate between theeffects ofproduce fromtreated animals against produce fromuntreated animals
because essentially theysitinthesame biological range. Inthecaseofthenon-naturally occurring
hormones, inestablishing theADI, thenthere wereverysensitive endpoints derived fromstudies in
non-humanprimates,andthenthesituationofsensitivemembersofthepopulationwastakenintoaccount
when establishing safety factors. Sothelevels thatonewould getinmeataresubstantially below those
causing anyeffects inprimates, andthere isareasonably good correlation inhormonal levels in,or
effects ofhormonal levels inprimates against humans. Sotherefore thelevels thatyouwould seein
meatfromanimals thatweretreated withthetwonon-natural growth promotants would notbecausing
effects inhumans iftheyconsume themeat.
Dr.Arnold
66. Mr.Chairman, thethreenatural hormones astheyendogenously occur atphysiological levels
certainly havebiological effects ofhuman beings. Thisistheirroleandtheirfunction. These steroids
areamongst themostsuccessful molecules which haveevolved andyoufindthemalready inverylow
species. Soitisquiteclearthatatphysiological levels theyhaveimportant functions andtheyinteract
withmany other hormones andtheyactalmost onevery cellinthebody. Now, theadditional amountWT/DS48/R/CAN
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youcould ingest withmeat, either fromuntreated orfromtreated animals according towhatveterinary
practices, cannot modulate thisendogenous activity ofthese hormones because theamounts aretoo
small.
Chairman
67. Itakethatthisisallsubject totheapplication ofgood veterinary practices. Itisalways the
big"if",asIreaditinyourpaper too,thatistheassumption.
Dr.André
68. Iagree withthatfactandIbelieve withmycolleagues thatwithin thephysiological range as
these hormones havenoacute difference biological effects onhuman beings. Butinthephysiological
range theproblem andthequestion istoknow ifwhen youtreatanimals orwhether youdon'ttreat
animals youhavethesame mean inthephysiological range. Imean Ibelieve thatifyouonlyeatmeat
from treated animals, youwillhaveasDieter Arnold said,averysmall enhancement ofthemean of
yourfoodhormonal intake andthiswillnotbetransformed inclassical biological effects forhuman
beings. Youdon'tseeanything, buttheproblem isthatsome other biological effects havenotbeen
studied andneedaveryveryverylongtimetobestudied. Ithink forexample, aschanges inhuman
fertility orchange insexratioasweknow thissexratioforexample isnowchanging insome countries.
Butwehavenorelation between these countries andthefactthattheybanned ornotthese hormones,
thatisnottheproblem now. ButwhatIonlysayisthatthischange inhuman reproduction forexample,
hasnotbeenstudied norrelated tohormonal change ornot,andIhavepersonally some doubt onthis.
Chairman
69. Thank you,Dr.Lucier.
Dr.Lucier
70. Theshort answer isyes,some biological effect could occur. Ifyouthink about interms of
anormal condition, sayanormal woman would have30percentofheroestrogen receptors occupied
atsome given point intime. Atthatsame point intime, ifsheisconsuming meat thatcontains an
additional burden ofoestrogens because oftheuseofgrowth promoters, thatreceptor occupancy may
besomething like30.01 or30.001, averyverysmall increase. Thisincrease would notbedetectable,
notevenclose tobeing detectable, byanyexperimental tools thatwehavetoday. Sotheanswer is
thatabiological effect could beoccurring, ifitisoccurring itwould notbedetectable, andfinally
therelationship between thatbiological effect andatoxiceffect, saycancer orbirthdefect orsomething
likethis,would beunknown. Butifsuchaneffect wasoccurring itwould beextraordinarily small,
remarkably close tozero.
Chairman
71. Thank you. Dr.Randell would youliketotakethefloor. Now? Aprocedural question or?
OK.
Mr.Christoforou (EC)
72. Mr.Chairman, thank you. During theorganizational meeting wehadthismorning, yousaid
thatwewould review howtheprocedure isgoing afterawhile andnowitisourfeeling thatitwould
probably beappropriate, aftertheUnited States hasposed thethreeorfourorfivequestions, soprobably
wecanstayhere, andthenCanada willcome upwiththefollow-up questions inthissame area, and
thenwetakeupthefloor ourselves, because thatisgoing toolongandwewould likeifpossible to
intervene inthisareaofresidue levels anddistinctions between thethreenatural andthethreesynthetic.WT/DS48/R/CAN
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Ithink thatitwould bemore appropriate andwillprobably improve thequality ofthedebate andthe
discussion wearehaving here. IftheUnited States cancontinue withoneortwomore questions and
Canada, andthenwecancome inatthisstagewithsimilar questions inthisareawhich youarediscussing
now.
Chairman
73. Wellmypersonal feeling isthatweareinagood process. Tomeitisveryeducational the
wayweproceed andIwould prefer tosticktothemodes wesetoutandyoucancome inwithaquestion
when it'syourtime. Youcanthenalsofocus onthepoints youwantbeing lessreactive thanwhen
youhavetofollow uptowhattheyaredoing. Ithink, it'smyassessment thatit'sefficient andof
course astimegoesby,lessandmore specialized question willbecome necessary andwewillfocus
andtarget more down andyouwillbring inother aspects thantheother parties. Iwould havea
preference tocontinue thewaywearedoing. Igiveyouthefloor.
Mr.Brinza (US)
74. Thank youMr.Chairman. Thenextquestion isrelated totheonewewere justasking. I
justwanttomake sureIunderstood theresponse correctly which is,would theresidues found inthe
meatbechemically identical whether itcame fromapplication forgrowth-promotion purposes versus
endogenously produced versus applied forzootechnical ortherapeutic purposes? Would itbethesame
chemical residue, recognizing thelevels again would bevariable?
Dr.Ritter
75. Ipresume thatyourquestion isdirected ofcourse tothenatural hormone?
Mr.Brinza (US)
76. Yes.
Dr.Ritter
77. Intheinterest ofexpediency Mr.Chairman, Iwillsayessentially yes. Essentially yes.
Dr.McLean
78. Mr.Chairman, theresidues willbesimilar forzootechnical useswhere quite highlevels are
used, youcangetspill-over orinhibition ofcertain ofthemetabolic pathways, andinthatwayyou
might getqualitatively similar butquantitatively quite different residue profiles.
Dr.Arnold
79. Thisisalsomyanswer,Mr.Chairman,qualitativelythesamebutquantitativelycouldbeslightly
different depending onthecompound administered, thedose, theroute ofadministration, etc.There
aresome differences.
Chairman
80. Thank you,yesDr.Ritter.WT/DS48/R/CAN
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Dr.Ritter
81. Iamsorry Mr.Chairman, justtoclarify, perhaps Imisunderstood thequestion, butwasthe
question directed atforthesame use,thatiswhat...
Chairman
82. Could yourestate?
Mr.Brinza (US)
83. Yes,thequestion waswould theresidue bechemically thesame whether itwasendogenously
produced, forexample, picktestosterone. Whether itwasendogenously produced testosterone,
testosterone administered forgrowth promotion purposes ortestosterone administered forzootechnical
ortherapeutic purposes.
Dr.Ritter
84. Then ofcourse Icertainly agree withtheanswer provided bymycolleagues. Qualitatively
theresidue inmyviewwould beindistinguishable. Quantitatively, ofcourse, theamount thatcould
bedetected would beafunction oftheamount thatwould havebeenadministered either forgrowth
promotion ortherapeutic uses.
Dr.André
85. Ithink thattheresidues areforthegreatest partoftheresidues thesame, when usedforgrowth
promotion natural hormones andforuseastherapeutic zootechnical. Ifdifferences appear itcanbe
inmetabolic profiles, Imean thatwiththelongtermeffect youinduce some different enzyme panels
andthisenzyme, afteralongtime, canproduce small amounts ofdifferent metabolites aswhen you
arejustusing these hormones onetime. Buttomyknowledge, thisisknown forother compounds
butnotforhormones, buttomyknowledge alsoithasnotbeenstudied.
Chairman
86. Thank you,Dr.Lucier.
Dr.Lucier
87. Yes.
Chairman
88. Thank you. Well, ifyouagree youdon'thavetotakethefloor, inorder towintimethatis
fine.
Mr.Brinza (US)
89. Thenextquestion Ithink Dr.Lucier willfinditaneasier timetoagree withbecause Ibelieve
Iunderstood astatement hemade thatgiven theconcept ofhalf-life, thatifyouadminister oneofthese
hormones toananimal, inthiscaseIamtalking ofallsixofthem, youadminister ahormone toan
animal therewillbearesidue, evenfaroutintothefuture, eventhough itmaybeonlysofewmolecules
itcould notbedetected byanyavailable means thatwehaveatourdisposal currently. Ijustwanted
tomake sureIhadunderstood thatandwhether thatwasthevieworwhatIhadunderstood fromthe
responses oftheother experts aswell. Please correct meifIhavemisstated.WT/DS48/R/CAN
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Dr.Lucier
90. Areyouasking mespecifically? Thatiscorrect afewmolecules would likely remain, not
detectable certainly, butthere isevery likelihood there would beafewofthem leftaround.
Dr.Arnold
91. Mr.Chairman,hormonesadministeredfromexogenoussourceshaveveryshorthalf-livesinitially
afteradministration, intherange ofminutes. Butthenthehalf-lives becomes longer andlonger because
these hormones gotodifferent compartments inthebodyandafterafewhours, thehalf-life isalready
intheorder ofsome 50,100minutes, initially itisintheorder ofsome 10-15 minutes. Soitisvery
difficult topredict forhowlongthelastmolecule willpersist inthebody, butcertainly foraverylong
time.
Chairman
92. Thank you.
Dr.McLean
93. Forthesakeoftherecord Mr.Chairman, Iagree withDr.Arnold.
Chairman
94. Younodaswell?
Dr.Ritter
95. Ifyouwould likeacomplete record, Yes.
Chairman
96. Wellitisnotnecessary, thank you. Canwegoon?
Mr.Brinza (US)
97. Iwould liketoturnnowtoquestions thathavebeenraised insome ofthedocuments thathave
beenprovided toyouallandmake surethatIhadunderstood correctly theresponses insome ofthese
instances. With respect tothestudies thatDr.Liehr hadperformed, Iwanttomake surethatweare
allunderstanding thatthedosecomparisons ofthestudies, thedoses thathewasusing inhisstudy
versus thedoses thatwearetalking about forgrowth promotion purposes. Ijustwanttomake sure
thatweallunderstood thisthesame way,thatthedosage usedinDr.Liehr'sstudy was61micrograms
perdayinthemaleSyrian hamster, which weighs approximately 100grams. Letmejustrunthrough
these, thenwecandiscuss thisalittlebit.Thatwould beapproximately 610micrograms perkilogram
perday,ifwearedoing ourmath correctly, andfora60kilogram adult malehuman thatwould be
equivalent toabout 36.6milligrams perdayandthatadultmalehumans produce about 48micrograms
ofoestradiol 17betaperday. Given thatmath then, whatDr.Liehr wasdelivering tothehamsters
inquestion was36,360/48 times more thanthecomparable average dailyproduction rateinadultmen,
andthatinturnis15,000 times more thantheresidue ofoestradiol inmeat from treated animals.
Ijustwanted tomake surethatwehadthenumbers there correctly, because thenthatwould leadto
result ofadifference between thedoseusedinthetreatment ofthehamsters andtheresidue in500grams
ofmeat, ofasignificant difference, itwould beequivalent totheoestradiol from11.5million 500gram
portions ofmeat being injected intoahuman male every daytobecomparable. Icanrunthrough
those numbers again, Irecognize thatwasrather fast.WT/DS48/R/CAN
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Chairman
98. Yes,theCommunity, Mr.Christoforou.
Mr.Christoforou (EC)
99. Ithink itwould beprobably more useful, ifwecangetthewritten version ofthese statements
andthenumbers.
Chairman
100. Well, Iunderstood itsabout hamsterizing humans.
Mr.Christoforou (EC)
101. Yes,indeed, butthere wassome other references toother animals, sowewould likereally
toseesome other products, sowewould appreciate itifwecangetthewritten version withtheexact
figures forustohavealook, thank you.
Chairman
102. Yes,Iassume youwanttocome backtothiscomparison lateron.Butareyouinaposition
toanswer orwould youpostpone thisneedoffigures? Dr.Arnold.
Dr.Arnold
103. Provided thatIcorrectly understood thequestion, Icanperhaps giveapreliminary answer.
Ifapellet isadministered tohamsters intheorder ofseveral milligrams 20,50ormore, youcanthink
about 100,150micrograms which arereleased perday.Therefore some authors insome studies have
simulated thissituation byconstantly infusing similar amounts totheanimals. Sothese areinfact
veryhighdoses which arereleased from suchimplants.
Chairman
104. Professor McLean.
Dr.McLean
105. Ifit'shelpful Mr.Chairman, Iwould takethesame lineasDr.Arnold. Itisquite clearthat
thedoseadministered tothehamster inapellet wasanumber ofmilligrams, ahamster weighs afew
hundred grams andtoextrapolate fromthework inthehamster tothehuman situation Ithink isfairly
dangerous.
Dr.Ritter
106. Mr.Chairman, without double checking allofthecalculations thatwerejustgiven tousvis-à-vis
thecomparisons, Ithink thepoint ofmycolleagues Professor McLean andDr.Arnold make isthe
correct one. Thatisthatthere isorders ofmagnitude difference here, between thedoselevels that
wereusedbyProfessor Liehr andthose thatmight result asresidues forexposure inthequestion of
meat. Ithink weneedtoremind ourselves thatthefundamental intent hereisdifferent. Thatis
Professor Liehr'swork andthework ofmany investigators istoproduce aneffect. Thisspeaks to
themostfundamental issueinpharmacology andintoxicology andthatistheconcept ofdoseresponse.
Professor Liehr isveryinterested inunderstanding theinduction ofcancer asaresult ofexposure to
thesehormones, soofcourse hisprotocol would necessarily bedesigned insuchaway,soastoproduceWT/DS48/R/CAN
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thedesired effect, inhiscasethetumour. Theintent obviously inthecaseoffood residues,
Mr.Chairman, istoavoid adoselevelwhich mayconstitute ahuman risk,soitwillcome assmall
surprise thatthelevels thatarepresent asresidues infoodarethousands orhundreds ofthousands
ormillions oftimes lower thantheywould beinanexperiment which isspecifically designed toinduce
atumour. These twoexperiments, ifyoulike,arecompletely atcross purposes witheachother. They
arefromtheirveryinitiation intended toproduce entirely different results. Sotocompare aprotocol
which hasbeendesigned toproduce atumour toafoodresidue theusedpractice ofwhich issetup
insuchawaysoastominimize thepresence oftheresidue, isinmyviewarelatively meaningless
comparison. Thank you.
Dr.Lucier
107. Iamnotinfundamental disagreement withwhathasbeensaid,butIthink itisimportant to
point outonething, thatphysiological levels ofoestrogen doresult inoxidative damage toDNA and
thishasbeenshown intheratandsothistypeofdamage doesoccur inphysiological situations in
experimental animals andthisisaparticular form ofdamage toDNA that'sbeenquantified. Sothe
levels thatarenormally circulating inthebodyareproducing someoftheseDNA damaging metabolites.
Exactly howitdoesit,isopentoquestion andwiththework ofDr.Liehr which would suggest one
way,other works maysuggest other ways, butIthink itisclearthatthatamount ofdamage isoccurring
andwould occur following asmall dosebecause itisalready added toanadditional body burden in
which thisisalready occurring. Butagain thatadditional DNA damage would extraordinary small,
again remarkably close tozero.
Chairman
108. Thank you. When youtalkabout physiological levels, may Itake itthatmeans
naturally-occurring levels?
Dr.Lucier
109. Thatisright. Ofcourse these change during thenormal cycling phases ofpeople aswellas
experimental animals, sothere isarange ofvalues thatoccur, butwithin thatnormal range ofvalues
thatyouseeinexperimental animals, which issimilar towhatisseeninpeople aswell.
Chairman
110. Thank you. Anyfurther remarks onthispoint?
Mr.Brinza (US)
111. Sorry, Ijusthadafollow uptothelastintervention. Ijustwanttomake sureIunderstood.
Isthereevidence thatatthelevels wearetalking about ofresidue inmeatfromtheuseofthesehormones
forgrowth-promotion purposes inaccordance withgoodanimal husbandry practice, isthere evidence
being putforward ofDNA damage from those levels ofresidue?
Dr.Lucier
112. Letmeanswer thequestion inanother way,perhaps Ihavecaused some confusion. Sayyou
alreadyhaveahundredorthousandmoleculesofsomethinginthebody,andthatsomeofthosemolecules
areproducing aDNA damage event. Ifyouaddanother molecule toitthere issome possibility that
thatsameevent willoccur because itisthesamemolecule. Youwillnotbeabletodistinguish certainly
thatadditional event fromtheonesthatoccurred fromthethousand molecules, butyouwon'tbeable
tosay,nononeofthose events arerelated tothatadditional onemolecule. ThatiswhatImeant thatWT/DS48/R/CAN
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itwould notbedetectable, veryverysmall, butitwould beimpossible tosaythatthatevent could
notoccur.
Chairman
113. CanIjustfollow upformyunderstanding. Thecomparison between Dr.Liehr'sprotocols,
inducing cancer ontheonehandusing veryhighdoses andontheother handusing veryverylimited
doses here. Isityourviewthatdespite oneusesveryverysmall doses, therestillmight besome effects?
Dr.Lucier
114. Yes,because youarealready adding toanexisting verylarge number ofsame molecules, so
justinstead of1,000 molecules youhave1,001 isirrelevant here.
Chairman
115. Andthatiswhyyoubasically challenge, ifIamcorrect, thattheconcept ofthresholds...
Dr.Lucier
116. Thatisexactly right. Ishould alsopoint outthough, tomake itclear from myview, thatI
donotthink ithasbeendemonstrated thatthisparticular mechanism isrelated orproven toberelated
tothecarcinogenicity ofoestrogens. Itisatthispointaninteresting hypothesis, theresome plausibility
toit,butithasnotbeenproven tobeassociated oracause oftumours produced byoestrogen.
Chairman
117. Yes....
Mr.Palecka
118. Thank youverymuch, sorry perhaps tointerfere intothediscussion. Justoneprecision: by
adding onemolecule, doesitmean thatthere isalinear increase inprobability ofDNA damage or
youthink thatitsprogressive? Does itmean thatitwillperhaps putsomething more oritisjusta
verylinear function?
Dr.Lucier
119. Itisalready adding toanexisting burden, ifthatburden thatalready exists isonalinear part
ofadoseresponse curve, thenadding anadditional molecule would create asmall amount ofadditional
damage. Itispossible thatthatmechanism isalready saturated maximal atthephysiological
concentrations, ifthatisthecase, thenthatdamage would notoccur, thisistheopposite situation of
thethreshold.
Chairman
120. Thank you. Anyfurther comments onthis? No,ok.Onemore.
Mr.Brinza (US)
121. Isaidonemoment please.WT/DS48/R/CAN
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Chairman
122. Ohonemoment, Isee.
Mr.Brinza (US)
123. Mr.Chairman, afewmore questions. Ijustdidwanttofollow uponthislastpoint. This
might getabittechnical soImayhavetoimpose ontheexperts tohelptranslate thisintoterms that
areeasily understood bypeople likemyself, whoaremore layperson thantoxicologist orscientist.
124. Let'smake sureIunderstood. Ibelieve Iunderstood reference toDNA damage. Ijustwant
tomake clear. IsDNA damage, inother words DNA adducts, always indicative ofagenotoxic effect?
Dr.Lucier
125. No.Doyouwantalonger answer? There isawealth ofscientific evidence toshow thatfor
many carcinogens aDNA adduct stepisessential. Formany ofthepolycyclic aromatic hydrocarbons
forexample, thatoccur ascontaminants andmany industrial processes atpresent inourair,there is
aspecific DNA adduct that'sbeenidentified thathasbeenshown toberelated asclose asyoucan
come inacausal sense tothetumours thatresult. Inother cases, some DNA adducts havenomutating
capability, sothere isawide variation. Notalladducts arealike, some haveverystrong mutating
potential, some haveweak mutating potential, others havenomutating potential atall.
Chairman
126. Sorry, would youliketotakethefloor onthispoint?
Dr.Arnold
127. Ithink itcould beinteresting tothePanel tonotethataverylarge number ofadducts toDNA
exists atalltimes inallcellsofthebody.
Mr.Brinza (US)
128. Thank you,Iwasabout toinvoke Dr.Arnold 'sname. Iunderstood earlier thatweheard that
asingle strand break inDNA actually occurs something intheorder of5,000 times perhour, Imay
nothavegotten allthiscorrectly, andthatthehuman ability torepair isabout 200,000 events perhour.
Ijustwasgoing toaskDr.Lucier whether theDNA damage thathewasreferring towould fallwithin
therange thatwearereferring tohere, thatDr.Arnold hadreferred toasnormally occurring.
Dr.Lucier
129. Ithink thatthekindofdamage thatwould result fromoxidation, catechol oestrogen formation
of17betaoestradiol, would result, andIamnotahundred percentsureofthatand, IamsureIwill
becorrected when theother folksstartasking questions, butIbelieve thatwould besomething called
8-hydroxyguanosine would betheprimary oxidative damage step.Youdon'tremember that,wewill
notgiveyouaquizlater, butthisoccurs inveryhighfrequency. Idonothavetheexact numbers,
butitdoesoccur inveryhighfrequency inthehuman body.
Chairman
130. Thank you.WT/DS48/R/CAN
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Dr.Arnold
131. Mr.Chairman, Ididnotwant tosuggest tothePanel thatweshould nottakesucheffects
seriously. Thisisthevalue ofthese indicator tests, ofthese early events, thatwegetconscious that
something ishappening toDNA andthatwefurther investigate. Theonlything Iwanted tosayis
thatsingle-stranded breaks areperseinsufficient evidence, particularly ifobserved invitroandyou
needtodofollow upstudies.
Chairman
132. Thank you.
Dr.Lucier
133. Iwould liketoaddonecomment tothat. Ithink thatthatisaverygood point. There are
alotofdifferent waysoflooking atgenetic damage andthescience ofchemical carcinogenesis evolves
orprogresses inittybittylittlesteps andeachpiece ofevidence addstothetotaldegree ofevidence
thatachemical isacting through thatpathway. Butsimply having apositive DNA adduct testora
positive cell-transformation testinitselfisnotconvincing. What becomes convincing when youhave
awhole bodyofknowledge fromcellsystems, fromexperimental systems, invivo,fromlimited studies
youmayobtain from human samples, andstartputting italltogether andthataddstothedegree of
compelling nature oftheevidence. Soitisnotlikenowwedonothaveit,nowwehaveit,itsort
ofgoesinastepwisefashion.
Chairman
134. Thank you. Would youliketocontinue Mr.Brinza?
Mr.Brinza (US)
135. Iftherearenoothercomments. Iwanted toaskacouple ofquestions withrespect totheconcept
ofanacceptable daily intake level, which wasexplained Ithought quite wellbyDr.Randell earlier.
Ijustwould liketomake surethatIunderstood, andfromtheexperts 'responses thattheywereusing
theconcept ofanADIinthesame way, which isthatitistheamount ofasubstance thatcanbe
consumed daily byhumans overalifetime without anadverse effect.
Dr.Ritter
136. Yes.
Mr.Brinza (US)
137. Thesilence means theothers weredoing itinthesame manner, using thesame manner? In
thatcaseconceptually would itbepossible toestablish anADIforthethreesynthetic hormones involved
inthisdispute, trenbolone, zeranol andMGA?
Dr.Ritter
138. Certainly inmyviewtheanswer isyes.
Dr.McLean
139. Theanswer from mypoint ofviewisyes. Iwould justliketoreiterate thattheendpoints
forbothofthemtookintoaccount sensitive subpopulations, sensitive human subpopulations, suchasWT/DS48/R/CAN
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pre-pubertal children andmenopausal women andalsothattheyweresupported bydatagenerated from
studies oradministrations tonon-human primates.
Dr.Arnold
140. Iagree withtheprevious speakers.
Chairman
141. Could perhaps Dr.Randell explain whywedonothaveADIs onthese hormones. Whywere
theynotestablished?
Dr.Randell (Codex)
142. Thedifference between thethree natural hormones andthexenobiotic hormones Ithink has
beendiscussed earlier today. Firstly, forthexenobiotic hormones itisrelatively simple application
oftheADIconcept andtheADIparadigm ifyouwishtoestablish ADIs forthese substances. For
theendogenous hormones, theJECFA looked attheavailable information, found thatbecause these
wereproduced inmanandthatthelevels ofingestion wereseveral magnitudes lessthanendogenous
production, thenitwasunnecessary tosetanADI. Onthebasisthattheendpoint would achieve the
same result, thatthere would benoadditional risktothehumans.
Chairman
143. Onthenecessity, isthatviewshared bytheother experts? Dr.Arnold?
Dr.Arnold
144. Mr.Chairman, itmight beinteresting tothePanel thatintheECwehavereviewed thethree
natural hormones independently from JECFA. Atleastaresult ofonesuchevaluation hasbeen
published intheOfficial Journal. WehavesetanMRL notnecessary foroestradiol twoyears ago
forthetherapeutic usesandthewhole evidence hasbeenreviewed bytheCommittee forVeterinary
Medicinal Products andtheEuropean Medicine Evaluation Agency. Since these arejustninelines,
maybe Icanreadtheconclusions oftheECCommittees anditslegally binding now, published inthe
Official Journal. "Theconclusions oftheFAO/WHO Expert Committee onFood Additives, JECFA,
thatnoADIandMRLs foroestradiol willneedtobeestablished, isadopted. Neck andplasma residue
levels after treatment withoestradiol benzoate andoestradiol valerate have shown tobewithin
physiological limits. Although itislikely thattissue residues levels willalsobewithin physiological
limits, thiscannot beguaranteed given theresults withoestradiol-hexahydrobenzoate. Stillcompared
tothelowesthumanproductionrateofoestradiolpre-pubertalboys,6microgramsperday,andcompared
totheamount ofoestradiol inother foodstuffs thatarepartofthehuman diet,theamount ofexogenous
oestradiol thathumans willbeexposed through ingestion oftissue fromtreated animals isbiologically
insignificant andwillbeincapable ofexerting hormonal effect inhuman beings." Soitisabout the
same lineofevidence andofarguments puttogether bytheECCommittee, thanhasbeenpreviously
donebyJECFA.
Chairman
145. Thank you. Isthisreference inyourpaper.?
Dr.Arnold
146. Yes,itis.WT/DS48/R/CAN
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Chairman
147. Thank you.
Dr.Arnold
148. AndifyouwantIcangiveyouacopyofthatCouncil Regulation.
Chairman
149. Please Dr.Randell.
Dr.Randell (Codex)
150. Iwould justliketostatethatanacceptable dailyintake isanumerical estimate ofwhatmight
becalled anoeffect level inhumans, withbuiltinsafety factors. However, inthebroad range of
substances thatJECFA hasevaluated overanumber ofyears, ithasonmany occasions notallocated
anumerical ADI. Thereason fordoing thisisthatcertain substances areessentially safetoingest
atanylevel andinthese cases JECFA willgiveanADIwhich itcalls"notspecified". Itdoesnot
specify theacceptable dailyintake. Verycommon safefoodadditives suchasascorbic acid,vitamin C,
fallintothisgroup. Onthese three substances were theonlythree substances inwhich JECFA has
usedtheexpression "notnecessary". Inthisparticular caseJECFA feltthatitwasnotnecessary because
oftheoverwhelming endogenous production byhumans ofthese substances andthattosetanADI
would notachieve anyadditional improvement inunderstanding ofthesafety ofthese substances in
humans. So"notnecessary" wasbasically anevaluation ofwhatJECFA wastrying toachieve ingeneral
interms oftrying toprotect health ofconsumers.
Chairman
151. Thank you. Further comments onthisorwould youliketogoon?
Mr.Brinza (US)
152. Thank youMr.Chairman. Ibelieve thatIhaveunderstood previously Dr.Randell andwould
liketomake sureandconfirm, thatintheinstance ofthetwosynthetics thatwerereviewed byJECFA,
ontrenbolone andzeranol, thattheADIwassetusing themethodology thatyoudescribed ingeneral
foranADI. ThatADIhasthesame meaning forthose twoasitdoesforother substances.
Dr.Randell (Codex)
153. TheADIforthezeranol andthetrenbolone wasestablished onthebasis ofano-effect level
being identified intestanimals. Inthesetwoparticular cases, theno-effect levelwhich JECFA selected
wasthenohormonal effect levelforbothsubstances.
Mr.Brinza (US)
154. Thank you. IfIcould turntoasubject thatwastouched onbyoneoftheexperts earlier today,
Iwilljustmake sureIunderstood correctly. Withrespect totheparticular implantation offiveofthese
hormones under discussion, what factors, ifany,make theearasasiteofimplantation favourable
foruseoverother sitesofimplantation?
Chairman
155. Would youliketotakethefloor?WT/DS48/R/CAN
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Dr.Ritter
156. Isuppose, following theorder thatwenowseem tohaveset,Mr.Chairman.
Chairman
157. Wellitisunfair thatyouhavetotakeit,justfeelfreewhen youwanttoanswer.
Dr.Ritter
158. Ithink theprimary impetus, Mr.Chairman, fortheselection oftheearisbecause itisatissue
which isnotnormally usedtoenter thefoodsupply, soitmakes identification ofthesource ofthe
material veryeasy. Idonotwanttosayensures, butitgoessome veryconsiderable distance toensuring,
thatinjection siteresidues, which understandably could bemuch higher thannormal tissue residue
levels, areextremely unlikely toenterthefoodsupply. Itismyunderstanding thatthatistheprimary
motivation forselecting asitewhich willnever enter thefoodsupply.
Dr.McLean
159. Andoneadditional advantage ofusing theear,itisveryeasytopalpate apellet oranimplant
under theskinoftheear,whereas ifitissubcutaneously onthebody thenyouwould never findit.
Sothatisasecond wayofidentifying treated animals. Infactforsome othertreatments withhormones,
butnotthese ones, itisactually possible toremove theimplant from theear.
Mr.Brinza (US)
160. IfIcould justfollow uponthat,Iunderstood areference earlier thatinfacttheimplants come
withadevice which isspecially designed toimplant thepellet intheear.Ibelieve Ihaveunderstood
thereference thatthatdevice would notbesuitable forimplanting itthrough thehide, forexample.
Ijustwanttomake sureIhaveunderstood thatcorrectly.
Dr.McLean
161. Iwould bealittlebitunwilling toextend itthatfar.Itisjustthatthe"gun" usedtoadminister
theimplants issuchthatitmakes administration convenient, easyandaccurate, inthatthepellets or
theimplants aregenerally inacartridge anditrotates around alittlebitlikeasixshooter andsoit
isaconvenient, easyandaccurate waytoadminister theprescribed dose.
Mr.Brinza (US)
162. Thank you.IfIcould thenaskwhether thereisanyspecific evidence thattheexperts areaware
ofevidence thatusing adoseofhormone greater thanthatapproved forgrowth promotion would lead
toaproportionately greater response infeedefficiency.
Dr.McLean
163. Generally not.When thesponsor suggests thedose, thenthedosethattheysuggest willgive
theoptimum response andsotherefore, within limits, thereisnoneed, noreturn inadministering more
thanissuggested. Thesecond thingis,however, mostregulatory authorities, including JECFA, require
thatdatasetting residues doestakeintoaccount doseratesthatareinexcess ofwhatisnormally used,
generally twice atleastandsometimes more, sothattheeffect ofoverdosing, ifyoulike,orvariations
inuptake, canbeseen.WT/DS48/R/CAN
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Mr.Brinza (US)
164. Thank youandthenifIcould justfollow on,Iamsorry didyou...?
Dr.Ritter
165. Iwasonlygoing toadd,Mr.Chairman, thatIthink Dr.Randell inhisopening comments
articulated inmyviewveryveryclearly, thenature ofthebalance thatonetriestostrike inestablishing
anADIandanacceptable usepractice. Ithink, inmyview, hemade thepoint veryverywell, that
tousetoolittleachieves nothing. Thatisonedoesnotobtain thedesired effect butatthesame time
results inaresidue. Todotoomuch, tousetoomuch, goesbeyond whatonecananticipate interms
ofaneffect. Sothatthecorrect istheonewhich isultimately recommended andthatisavalue which
willoptimize thebalance between thereturn, thebenefit ifyouandtheresidue. Thatisthelevelto
which wearereferring.
Dr.Arnold
166. Mr.Chairman, inthedevelopment byindustry ofthese pellets andanother devices, theyhave
beenoptimized withrespect tothedose. However thisdoesnotnecessarily prevent some farmers
tousemore implants, forexample. Butthisagain doesnotnecessarily cause higher residue levels
inthecarcass. There aresome examples thatIhaveshown inmywritten response, where theuse
ofuptosiximplants didnotnecessarily havetheeffect thattheresidue levels intheremaining carcass
weresignificantly higher. Soitisaquestion youcannot easily answer, youhavetoanswer onacase-by-
casebasis. Ontheother side,itisquite clearthatifyouinject twice theamount directly, thatthen
alllevels increase inplasma andintissues, notnecessarily inalinear way,buttheyincrease significantly,
ifyoudouble thedose, forexample byinjection. Thatisthedifference between aslowrelease device
andadirect injection. Ontheother hand thelongtermrelease ofhighdoses mayhaveinfluences
onthepattern ofhormone excretion intheanimal 'sbody andthisistheintention ofusing such
compounds.
Chairman
167. Thank youverymuch. MayIjustmake, ohsorry, yes,please.
Dr.André
168. Justonecomment onthispoint. Itisnotsoevident thatadouble dose, evenatthesame time,
willgiveabetter response. Butwhat weobserved alotofyears agoinourcountry, when these
hormones wereallowed byimplants intheear,isthatfarmers triedtoputanother ofthesame doses
butlater. They donotwaitthewithdrawal period andtheyinject another onemaybe atthehalfof
thetheoretical withdrawal period, andtheyhadbenefit todothis,clearly, because theeffect wasmore
longer atthetime. Consequently itisclearalsothatrespecting thestrict withdrawal period attheend,
theresidue levelwashigher. Doyouunderstand?
Chairman
169. Yes. Myquestion would be,doyouthink thiswastypical forEuropean situation oristhat
aphenomenon which isobserved world-wide?
Dr.André
170. Itisnotascientific question, butthen, wellIthink really itisnottypical foranycountries.
Itisaproblem offarmer, ofrespect withregulation andofbenefits thattheyhave. Icanreturn through
thesame question, doyouthink people drive faster thanallowed inanycountry orinanother one?WT/DS48/R/CAN
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Itisaproblem ofrespect ofregulation, only. Butitisclearthatitwasthesame situation atthattime
inFrance asitisnowinUS,forexample. Because oneimplant wasallowed intheearwithawithdrawal
period, itisquite thesame situation itwasjust10years ago. Thatsituation seems tobethesame,
Ithink.
Chairman
171. Thank you. Would youliketocomment onthispoint?
Dr.McLean
172. Ijustwould liketomake acomment. Generally, ofcourse, forzeranol andtrenbolone the
useofexcess would beorcould bepicked upiftheMRL wasexceeded, andsotherefore there would
beapenalty iftheMRL wasexceeded. Andsotherefore, farmers knowing thatyoucananalyze for
quite accurately, orscreen forandconfirm, thepresence ofzeranol ortrenbolone arenotgoing to
dothat. Andtheother interesting thing isthatincountries where theuseofthese compounds is
permitted andthere aregood educational campaigns forfarmers astothecorrect useandthereasons
whyyoushould notexceed theprescribed dose, andthepenalties thatexistifyoudo,theresults from
residues surveys show thatbyandlargethereisnoexceeding oftheMRL. However inthose countries
where theuseisnotcontrolled andthatisnofarmer education campaign anddifficult toapply apenalty,
thenweknow thattheMRL issignificantly exceeded. Sooneoftheimportant factors oflegalizing
thesecompounds istobeabletoconduct aneducation campaign andtobeabletoputinplacemonitoring
campaigns toseethattheMRL isnotexceeded.
Chairman
173. Thank you. Dr.Arnold.
Dr.Arnold
174. Mr.Chairman, inJECFA weuseatermcalled theoretical maximum dailyintake. Thatmeans
wemultiply arbitrarily highconsumption figures withMRL figures, tocalculate whatcould happen
intheworse casescenario. Ifyouassume allanimals aretreated, allareattheMRL andunder these
conditions about fivepercentoftheADIisusedwithzeranol andtrenbolone. Itwasveryinteresting
formetoseethatinthedocumentation ofthe32nd JECFA there wasanexample ofverybigabuse.
Itwasintentionally donethisstudy, andItellyouwhatpeople haddone. They hadadministered a
dosemore than100times higher thantherecommended dose. Theyhaveadministered itintravenously,
insixdoses overthree days, soreally itisascenario youcannot more exaggerate. Under these
conditions thetheoretic maximum daily intake wasincreased byafactor ofthree, sothatwewerein
theorder of15-16 percentoftheADI. Thisismycomment, toshow thepotential consequences of
misuse orabuse ofthese substances. Wehavesome data,andthisdatahadbeenavailable tothis32nd
JECFA.
Chairman
175. Thank youverymuch. Wearepastoneo'clock andIwonder, doyouintend tocontinue with
thequestions forsome time, Isuppose.
Mr.Brinza (US)
176. Well, Mr.Chairman, actually Iwasabout tosay,looking attheclock, thatitmight beofsome
relief toyouandthePanel andothers thatweonlyhaveoneortwomore questions, relatively short
ones...WT/DS48/R/CAN
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Chairman
177. Ifwecould finish theUSquestions andthenwewould break. Would youagree tothator
would youneedabreak? Well, yes.Ifyouagree whydon'twefinish yourquestions andthenbreak.
Thank you.
Mr.Brinza (US)
178. Justaquick follow upIbelieve totheanswer wereceived earlier. Isthere anyevidence that
implantation oftheapproved implants atasiteother thantheearwould leadtogreater feedefficiency?
Inother words, isthere anyreason toimplant itsomewhere elsetogetabetter effect?
Dr.McLean
179. Ithink thegeneral consensus would bethatproviding itsubcutaneously, probably not.
Mr.Brinza (US)
180. Onefurther question, thereareseveral hormonal compounds thatareusedforasoestrus control
intheEuropean Union andamong these aremedroxy progesterone acetate andallyltrenbolone and
another compound methyl testosterone isalsousedforsexreversal inaquaculture, weunderstand.
Thequestion, though, iswhether these compounds arechemically related tothesynthetic hormones
usedforgrowth promotion inanimals.
Dr.Ritter
181. Mr.Chairman, Iliketheuseoftheword related because itprovides onewithenormous scope.
Ofcourse theyarerelated. They arestructure-related andtheyhaveactivity andfunction which is
similar tothehormones thatwearediscussing hereatissue. Butofcourse therearenotable differences
aswell, sotheyare"related", Ithink isagood word touse.
Dr.Lucier
182. Yes,Iwould agree withthatcomment thatchemically theyaredifferent. Intotal, butthey
veryhaveconserved partsofthemolecule andtheyperform orstimulate cellsinmuch thesame way.
Nevertheless, since theirpartsarealittlebitdifferent, theywillbemetabolised different soyouwill
havesome different breakdown products, youwillhavedifferent, theymaygotodifferent parts of
thebody, preferentially because ofthose differences inthemolecule. Sotheywillactpretty much
thesame wayoncetheygetintoatissue, buttheamount thatgetsintoatissue might bequite abit
different, oritsbiological persistence inatissue orcellmight bequite abitdifferent.
Chairman
183. Thank you. Dr.Arnold.
Dr.Arnold
184. Twosubstances named bytheUSdelegation arecertainly chemically related andalsowhat
concerns themechanism ofaction, there aregreat similarities. Nevertheless, allyltrenbolone isnot
useful forgrowth promotion, ithasnoanabolic properties andtherefore there isanexemption inthe
ECdirectives concerning thissubstance.WT/DS48/R/CAN
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Chairman
185. Thank you.
Dr.McLean
186. Generally Iaminagreement, except Ithink wealsoshould notethatmethyl testosterone is
more active orally thantestosterone andIthink allyltrenbolone isactive orally aswell. ButIthink
weshould notethattheoralactivity ofthose twocompounds ishigher thantheoralactivity ofthe
chemically related compounds. Thatistheonlypoint Imake.
Chairman
187. Thank you. Yes,Professor Arnold.
Dr.Arnold
188. Iagree withwhathasbeensaidabout therelation between hormones theyarerelated. Itis
agoodword. Butwehavejusttocompare whatiscomparable. When wespeak about thesehormones
wehavetospeak onlyabout thetherapeutic andzootechnical usesofthehormone inquestion andnot
about growth promotion. Itisverydifferent, because theyareusedpunctually (?)onanyindividual
orgroups, welldefined, ofanimals soitisverydifferent. Itisnotthesame use.
Mr.Brinza (US)
189. Thank youMr.Chairman. Ijustwanttothank alloftheexperts fortheirassistance andthank
thePanel fortheirpatience.
Chairman
190. Thank youverymuch. Thisbrings ustotheendofthismorning 'ssession. Ihave the
impression thatthelearning ratethismorning wasmuch higher thanitusually isinthese rooms and
Iwasveryimpressed. About timing, could wecontinue atthree o'clock withthequestions bythe
European Community? Could wedoitthree o'clock sharp, otherwise wemayrunintonight. Do
youhaveaprocedural point, Mr.Christoforou?
Mr.Christoforou (EC)
191. When would weexpect thedocument bytheUSonthese quantities ofmicrograms?
Chairman
192. Could youarrange tohandthem over
Mr.Brinza (US)
193. Mr.Chairman, wedonothavecopies withusbutwecancertainly provide thattoyouwhen
wereconvene.
Chairman
194. Thank youverymuch. Themeeting isadjourned.WT/DS48/R/CAN
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Mr.Christoforou (EC)
Mr.Chairman andMembers ofthePanel, Ladies andGentlemen, Experts advising thePanel
195. Ithink itisthenormal practice toallow thisdelegation topresent itself, ifyouplease excuse
me,because there aresomany scientists fromsomany places. Ithink fiveminutes orthree minutes
presentation byallthedelegation might behelpful asthese scientists willbeintervening inthisdebate.
Since theECdelegation isknown tothePanel, itisthenormal composition ofthedelegation, Iwould
onlyrequest scientists which areadvising theEuropean Community inthiscasetopresent themselves
verybriefly towards onwhattheyhavebeenuntilnow.
196. IwillstartthenwithDoctor Liehr onmyleft-hand sideplease.
Dr.Joachim Liehr (EC)
197. Mr.Chairman, myname isDr.Joachim Liehr andIamachemist andhaveworked forthe
last17years onthemechanism ofoestrogen-induced tumours. Thismechanism Ihaveconcentrated
on,thegenotoxicity studies, because everybody knew atthetimewhen Istarted these studies that
oestrogens arehormones andmany people accepted thefactthathormonal agents actashormones and
itwasatthesame timeclearthatoestrogens arecomplete carcinogens. There arequite anumber of
animal model systems where oestrogens arecomplete carcinogens without anyother agents. Soin
order toexamine thiscarcinogenicity effect, complete carcinogenicity effect, Iwanted toknow can
oestrogens alsoactasgenotoxins inaddition to,notseparate of,butinaddition to,thehormonal effects
thattheynormally exert. Thishasresulted inanumber ofpositive genotoxicity effects notjustinvitro
butalsomany ofthem invivoandquite adifferent class, many different classes ofgenotoxicity, so
thatwecantalkinthewords ofDr.Lucier ofcompelling evidence thatthere isgenotoxicity by
oestrogens.
Dr.Ercole Cavalieri (EC) oftheCancer Institute University ofNebraska Medical School
198. Iamherebecause alsoIhavedonefromadifferent approach whatDr.Liehr hastriedtoattempt.
When Istarted myresearch inchemical carcinogenicity Ihaveastrong feeling thatoestrogen isthe
origin ofmany human cancers, andittookmore than25years toresolve theproblem. Mr.Chairman,
thathappened because inorder tounderstand howoestrogen induced cancer, could initiate cancer,
wehavestudied alarge classofmoderate compounds called polycyclic aromatic hydrocarbons which
induce cancers andarepresent, many ofthem, inourenvironment, from thecombustion oforganic
material likegasoline, etc.These compounds havebeenanexcellent model forunderstanding how
oestrogen induced cancer andwearenowatthepoint inwhich wecansaythatoestrogens areinitiating
cancer andbytheso-called receptor-mediated process incancer andproduce cancer. Therefore my
point incontention isthatsince theyinitiate cancer forpeople thattheydonothavetheprotective
mechanismthatnormallyeverybodyshouldhave,evenaminimaldosethatcanimbalanceourequilibrium
could beafactor ininducing cancer tohumans. Iwould beverygladtoexpress thisinamore visual
waywiththeslides laterduring these procedures ifIcan.
Dr.JimBridges (EC) from theUniversity ofSurrey inGuildford
199. Iamprofessor oftoxicology andIsitontheScientific Committee onAnimal Nutrition for
theEUandtheUKVeterinary Products Committee. Myinterest ismechanisms oftoxicity andtheir
useinriskassessment.WT/DS48/R/CAN
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Dr.ManfredMetzler(EC)-ProfessorofFoodChemistryandToxicologyattheUniversityofKarlsruhe
inGermany
200. Ihavebeentrained asachemist andworked infieldofbiochemical toxicology formore than
20years. Mymajor interests overtheyears havebeenthebiochemical mechanisms ofoestrogen and
hormonal carcinogenicity andmore recently wehavefocused onthechromosomal effect ofoestrogens
ascarcinogens, which wethink isanimportant aspect ofhormonal carcinogenesis.
Dr.Alan Pinter (EC)
201. Iamapathologist bytraining andIhave been involved inmutagenesis oestrogen and
carcinogenesis forthelast15to20years. Now IamattheNational Institute ofPublic Health in
Budapest, Hungary. Thank you.
Dr.Samuel Epstein (EC)
202. Iamapathologist bybackground. Ihaveworked forsome three tofourdecades inproblems
ofcarcinogenesis andtoalesser extent inmutagenesis. Mymajor interests areinpublic health and
preventive medicine. Ofrelevance inthisconnection Iwasakeyadvisor totheUnited States Congress
intheearly70sinrelation toaseries ofactions leading totheeventual banning ofDES, having analysed
DESresiduedatawhichweobtainedfromavarietyofsourcesincludingFDAandUSDA.Mytestimony
wascritical tothebanning oftheuseofDESasananabolic.
Dr.Reiner Stephany (EC)
203. Iamachemist and25years involved inresidue analysis ofanabolic agents, alltypes ofanalysis,
research, development, regulatory, forensic, whatsoever. Thelastyears Iamfocused onthequestion
ofthereliability ofanalysis, forwhat purpose andforwhat price. Iamemployed withtheDutch
National Institute ofPublic Health andtheEnvironment andinvolved inECgroups andCodex groups
andsoon.
Dr.Adolfo Pérez-Comas (EC)
204. Iamapediatric endocrinologist, Associate Professor ofPediatrics Endocrinology inthe
University ofPonce inPuerto Ricoandprior withtheUniversity ofPuerto RicoMedical Science
Campus. Iamalsoanadvisor fortheCentre forDisease Control andforNIA, National Institute of
Health, ontheareaofdiabetes. Iamanadvisor ondiabetes andtechnology forHEW intheUnited
States.
Mr.Christoforou (EC)
205. Asyouseethere isonescientist missing andthisisDr.Adlercreutz, whounfortunately could
notjoinustoday buthewillbewithustomorrow. Heinformed methathewould onlyliketomake
averyshort statement, lessthanfiveminutes, when heisintheroom andbewilling toreply to
statements andquestions since hispaper hasbeenreviewed andcriticized bothbytheUnited States
andCanada. Mr.Chairman, while Ihavetheflooronemore procedural issueisthattheUnited States
hasargued against thesubmission ofanyevidence, newevidence inthiscase. Wehaveheard that
thismorning inthePreparatory Meeting, andyetwehaveseentoday afairly longdocument circulating
commenting onthereplies ofthescientists. According totherulesoftheDSU, thisdocument should
notcirculate unless itisreadout.TheCommunity would agree thatitiscirculated ifwearegiven
thechance toprovide asimilar document within averyshort time-limit. Thisdocument iscirculated
soIdonotknow thestatus ofthisdocument. Ifitistoremain, Ihavenoobjection, butitstays with
thefilesofthePanel, butwearegiven thechance ofthree daysmaximum orfourtoprovide similarWT/DS48/R/CAN
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documents inthisrespect. Ithink thatwould beaccording totherules oftheDispute Settlement
Understanding.
Chairman
206. Mr.Christoforou, would yougiveustherulewhich prescribes thatevery document hasto
bereadout?
Mr.Christoforou (EC)
207. Mr.Chairman, theruleisthatevery timewemeet yousayplease givethewritten version
ofyouroralstatement otherwise youcannot filedocuments withthePanel. Ifyouprovide alimited
interpretation tothatpractice Icanprovide documents without reading them. ButIremember the
argument wasmade bytheUnited States inoursecond substantive meeting where theywould like
thatwereadliterally thedocuments thatweweresubmitting. Thisistheruleandastandard practice,
anditisthesubmissions intheannex giving thetableofthedispute settlement, itisthewritten version
oftheoralstatements willbeprovided. Itisintheannex oftheDSU. Icanprovide youwiththe
exact provision.
Chairman
208. Wedoinvite, wehaveinvited youinfact,tosubmit yourcomments inwriting, butthiswould
notmean thatyouhavetoreadthem outbecause Iusually encourage people tosummarize whatthey
handininwriting instead ofreading itout. Ithink itshould notbeaproblem ofyouhaving such
adocument submitted within ashort period oftime-three days-okay.
Mr.Christoforou (EC)
209. Thank you. Mr.Chairman, wehaveheard carefully thesummarizing thatwasmade bythe
distinguished experts advising ofthePanel inthiscaseandwewould liketotackle anumber ofresponses
thatwere given tofirsttheirinitial presentation andthenthewaytheUnited States andanumber of
thequestions posed bytheUnited States.
210. Thefirstquestion would relate towhatwediscussed thismorning inthisroom. Physiological
levels ofresidues ofthese hormones inthehuman body. Ofcourse thisrelates tothethree natural
hormones onlywhich occur naturally, itdoesnotrelate tothediscussion onthesynthetic xenobiotic
hormones. Itisalsofrequently referred tointheJEFCA report of1988, where sometimes reference
ismade thattheresidues, forexample, ofoestradiol, would beincreased from twotofive-fold but
thiswasstillconsidered tobewithin thephysiological normal physiological levels. Inthiscaseand
inthisrespect IhaveDr.Epstein whowould liketomake atwo-minute explanation thenaskaparticular
question andIthink, Iunderstand from theSecretariat, apaper iscirculating thatgives theexact
calculations ofthose so-called physiological levels. Thisisimportant inourviewbecause welater
linkthistothemostsensitive partofthepopulation -theso-called pre-pubertal boys, andthevalues
thattheyhavegiven fordaily24-hours concentration ofoestradiol, because thisisanimportant issue
inourview. SoIwillgivethefloor toDr.Epstein please.
Dr.Epstein (EC)
211. Thank you. Ifirstofallwould liketothank theChairman ofthePanel forallowing methis
opportunity toaddress youbriefly. Before Icommence mybriefstatement Ihavejustbeenreminded
thatIneglected togiveyoumyprofessional affiliations, which isProfessor ofEnvironmental and
Occupational Medicine attheSchool ofPublic Health inChicago.WT/DS48/R/CAN
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212. TheJEFCA document andpreceding documents clearly givetheimpression thatresidues of
natural anabolics fallwithin thenormal physiological ranges asindicated previously. There isalso
aclearstatement thatlevels inmuscle arenormal. There isalsothestatement thatlevels inpre-pubertal
boysareabout sixmicrograms aday,which isroughly athousand times theresidue levels ofoestradiol.
213. Iwouldnowliketocommentonthesestatementsandpointoutthattheyappeartobeinconsistent
withindustry datawhich Ibelieve areavailable andhavebeenavailable toJEFCA andother bodies.
LetuslookfirstofallatthedataforSynovex Swhich isoestradiol andprogesterone andwhen you
examine levels ofoestradiol inliveryoufindtheyincrease six-fold, inkidney nine-fold, inmuscle
twelve-fold andinfattwenty-three fold. Sothatdoesn 'tappear tobeentirely consistent withwhat
weheard thismorning: namely thatmuscle levels arenotincreased when infacttheyincreased twelve-
foldandatwenty-three foldexcess forfathardly appears tobetrivial. Now these relate ofcourse
justtothelevels oftheparent oestradiol, andnotofcourse itsmetabolites, sotherefore thisrepresents
anunderestimate ofthetruehormonal residues inthemeat.
214. Turning nowtothequestion ofthefactor ofsixmicrograms adaybeing athousand times the
residue levels ofoestradiol forpre-pubertal boys: thispre-pubertal data, however, doesnotrelate
tochildren andenfants fromtheageof0to8.Nowbased onIARC documentation, volume 21,1979,
page42to46,youcanmake theverysimple calculations showing whatarethelevels ofoestradiol
production daily forchildren ofthisageanditturns outthatthelevels range from 0.16 to
0.8micrograms aday. Sowearenowshifting thelevels inpre-pubertal boysfrom sixmicrograms
to0.16. Thisisimportant fortworeasons: firstofallthefigure ofsixisclearly misleading and
secondly ourlevelofconcern isverymuch greater forinfants andyoung children andchildren under
theageofeight, because there isabundant dataonthemuch higher levelofsensitivity tocarcinogens
ofyoung children thantoadults. Soforthese tworeasons, Ithink itisimportant tofocus onthis.
Infactthemathematics clearly show thatthemargin ofsafety, theso-called margin ofsafety orthe
excess overbackground levels, isnotathousand-fold butsayforfatitiseight-fold, lessthananorder
ofmagnitude. Itranges fromeightto40,lessthananorder ofmagnitude atthelower level. Sothese
aresome veryfundamental distinctions andmisapprehensions onthese conceptions which Iwould like
tofocus on.
215. Allthisrelates purely tothelegal application. Theapplication conformance withstandard
recommended good husbandry practice. IfImayturnforthemoment totheillegal, Ishould liketo
preface mycomments ontheillegal byquoting from areference thatDr.Ritter kindly provided us
with; namely thereference toTruhaut in1985 whostated thattheunlawful useoftheanabolics can
result inresidues 300-fold inexcess oftheestablished tolerances. Irepeat, theunlawful usecanresult
inresidues 300-fold inexcess oftheestablished tolerances. Ihavenotreviewed theoriginal paper
ofDr.Truhaut butIrelyonDr.Ritter 'sreference toitandthestatement -thequotation -hemakes
from it.
216. Thesecond point inthisconnection Ishould make iswhen wearetalking about illegal or
misplaced implants, wearenottalking about anoccasional liberation byanirresponsible farmer. We
aretalking about twothings: firstofallabout common practice asIwillprove inamoment. Secondly
wearetalking about asituation inwhich toallintents andpurposes thereisnoreasonable orpracticable
wayofmonitoring whether ornotillegal practice iscommon ornot. Irefer youtoa1986 USDA
survey ofsome 32major feedlots intheUnited States where halfthecattle werefound tohavemisplaced
implants. Irepeat, wearenotdealing withanoccasional abberation ofanirresponsible farmer. We
aredealing withacommon place situation inwhich thereisnowayofmonitoring, ofresidue analysis,
ofpractical residue analysis, sohowcanweevenbegin todiscuss concepts ofADIifwedonothave
theslightest level, slightest idea, ofthekindofresidues. Wealready know thatwhen administered,
when thehormones areadministered inaccordance withrecommended practice, thelevels areway
inexcess ofwhatyougentlemen havebeenledtobelieve. Butwhen itcomes tothemisplaced implants
wehavetwosetsofproblems. Oneyouhavetheproblem attheimplant siteinwhich itcould beargued
thatinfactinspectors regularly check every piece ofthemeatandiftheyfindanimplant theywouldWT/DS48/R/CAN
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cutoutthataffected piece ofmeatanddiscard it.Itisquestionable whether infactthathappens and
ourfriends from USDA mayperhaps bewilling togiveustheassurance thatevery portion ofevery
animal slaughtered isinspected formisplaced implants. Butfarmore tothepoint thefactiswhen
youimplant, putanimplant intheavascular, thenon-vascular subcutaneous tissue under theskinof
theear,therateofabsorption isextremely low,butwhen youimplant itinmuscle which ishighly
vascular, youcanhave amuch higher rateofabsorption. Now Ihavesearched theliterature as
thoroughly asIcould andcannot findanyreference oranydataatalllevels ofhormones ofoestradiol
atsitesatadistance fromtheimplant site.Thebasic knowledge ofpharmacology could make itvery
clearthatwhen youimplant ahormone oranyagent inahighly vascular tissue thenitsratesofabsorption
would bemany-fold higher, whether it'soneorder ofmagnitude, twoorders ofmagnitude, threeorders
ofmagnitude -Idonothavetheslightest idea,butIdoknow thatmisplaced implants arenotuncommon
andIdoknow from theindustry datathatthelevels oftheresidues, arewayinexcess ofwhatyou
havebeenledtobelieve.
Mr.Christoforou (EC)
217. Iwould likenowtoraise twoquestions, afterthestatement ofDr.Epstein, andtoallour
scientists advising thePanel. Ifitiscorrect aswehavebeenmaking thecalculations, andthedocument
iscirculating,aboutthelevelofoestradiolinpre-pubertalboys,whichisnotsixmicrogramsper24hours
butitiseight-fold lessthanthephysiological levels, thenIwould request thescientists togiveustheir
view: Isthisreally arisk,anadditional oranincreased riskofthese residues causing theriskswe
havebeendiscussing hereamong other things carcinogenicity, tothistypeofsensitive partofhuman
population? Thisisthefirstquestion, thank you.
Chairman
218. Thank you. MayIinvite youjusttocomment generally onDoctor Epstein 'sthesis, because
wewould liketohaveyourreaction onthis? Whowould liketotakethefloor? Doctor Ritter, please.
Dr.Ritter
219. Thank youMr.Chairman. Ioffer to,Ifoolishly offer toleadonlybecause Ithink Iwould
liketoclarify forthePanel aspecific reference thatDr.Epstein made tomysubmission withregard
totheTruhaut reference. Itiscorrect indeed thatIcitedthisreference, butIwould submit tothePanel
thatthereference hasbeensomewhat misquoted. Asapoint ofclarity, Dr.Epstein didcorrectly note
thatIrefertothepossibility ofthe300-fold excess inresidues withoestradiol.
220. ButifImay, Mr.Chairman, andIwillprovide specific reference tothePanel andtotheEU,
Ihavebrought italong willme.Buttoputintoproper context what theauthors havesaidexactly
isthat"when 50milligrams ofoestradiol inanoil-injectable preparation isadministered intra-muscularly
intheneckofavealcalfthree weeks prior toslaughter" andthentheygoontotalkabout thisillegal
practice, "thelevels ofresidues inthevicinity oftheinjection sitemaybe300-times greater".
221. Thisisapivotal issue, Mr.Chairman, because infactthere isnotaninjection atissueforthe
proper use.Sothisparticular three-fold increase inresidues refers toamultiple ofabuses, ifyoulike.
Itwould beatthewrong siteandusing thewrong method ofadministration. The300-fold increase
inpotential residue doesnotrefertothenormal use.Thisrefers toanextraordinarily abnormal use.
Thesame authors inreferring tothatveryconclusion thattheyhavedrawn thengoontosayintheir
conclusion: "Itisourbelief thatneither 17betaoestradiol norzeranol, poses anytoxicity problem
when usedasananabolic inanimal production. Itiswidely agreed thatintheinstance ofhormonally
mediated toxicological effects including carcinogenesis, atolerance level canbeset". They finally
conclude "even intheinstances inwhich misuse mayhaveoccurred, itisvirtually impossible tovisualize
anyhazard tohumans ingesting meatfromanimals treated withzeranol". These aretheirwords, not
mine.WT/DS48/R/CAN
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222. Imake thispoint ofclarity because IdidnotwantthePanel leftwiththeimpression thatthis
300-fold increase towhich Ireferred issomething thatcould beanticipated, ifyoulike,under normal
circumstances, andindeed astheauthors suggest itisnotlikely thatonecould anticipate itevenunder
abnormal conditions ofabuse. Itsimply demonstrates thanonecancreate ascenario where atthe
injection site,which would notbeapplicable innormal growth promoting uses, itcanbeinexcess.
Chairman
223. Whowould liketospeak tothequestion submitted bytheCommunity?
Dr.McLean
224. Justtomake acomment about thereaction totheimplant ifitisplaced intheearcompared
withinthemuscle. Ofcourse inthose vascular tissues likethemuscle thenyougetquite anactive
tissue reaction andindeed yougettheimplant walled off. Oneofthefeatures ofinjections
subcutaneously intheearisthatyoudonotgetthemassive reaction atthesiteanditisspecifically
designed, andalltheresidue studies arecarried out,withtheimplant injected intheear.Theaim
ofinjecting itthere istogetprolonged andslowrelease atlowlevels overaperiod oftime; sothat
isspecifically designed tobethatway.
Chairman
225. Thank you. Could youofferanycomments onthetableweweregiven andinparticular the
impact onthepre-pubertal situation? Youdonothavetospeak. Letmeknow. Yesplease Doctor.
Dr.Arnold
226. Chairman, there isoneproblem when thisinformation comes soquickly, ittakes some time
tolookattheevidence. Theonlything Icandoatthemoment istoconfirm thatthese figures really
stand intheIARC report involume 21.Itisimportant tonotethatthese values differ tremendously
according tothesource. SoIcan'tsayfromwhere thislevelofsixmicrograms came. ThisIdonot
know currently, butIhavesome tables fromsome textbooks ofendocrinology withmeshowing that
there isatremendous range andifyoureadcarefully thetextinwhich IARC explains thewayhow
theyhaveestimated, theymake quiteclearthatthisisanestimate andthatthevariability canbeenormous
andtheygiveexamples ofindividual goods where therewasaverylargerange ofdata. Sothefigures
areokay, butyoucannot insist andsaythisistheone.
Dr.Ritter
227. Thank youMr.Chairman. Ioffer onlytwopoints forconsideration bythePanel. Ithink
asDr.Arnold hasalready noted weareresponding somewhat onthefly,eventhough yousuggested
thatweneednotfeelanyobligations todoso.
228. Inthetablewehavebeenprovided, Mr.Chairman, theintake factors thathavebeencalculated
arebased onapproximate levelofexposure to500grams ofmeat. Thistablehasbeencalculated on
thebasis ofpre-pubertal boysunder eight years ofage. Iwould suggest toyouMr.Chairman that
itisnotlikely thatachild oftwoorthree willconsume 500grams ofmeataday. Thiscalculation
isbased ondaily intake ina500gram sample offood, every dayforhisentire life.Iwould submit
toyouMr.Chairman thatasamember oftheJEFCA process nowforsome years, Ifeelthatthe
500gram estimate isanover-exaggeration eveninthecaseofadults. ButIthink topresume in
calculating therisksthatachild under eightyears ofagewillconsume 500grams ofmeatevery day,
respectfully Sir,Ithink itissomewhat ofanexaggeration.WT/DS48/R/CAN
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229. Theother point thatIwould bring toyourattention andagain Iapologize forresponding on
thefly,isIthink thepoint thatDr.Arnold hasalready elaborated onandthatisthatthenumbers that
youseebefore youarepresented as,howshallIputthis,asiftheywererigidwhen infacthormone
levels, either present asresidues ornormally circulating endogenous levels, youwould normally be
accustomed toseeing them asarange. These donothaverigidvalues. Ifyoulook, forexample,
atthe,letustakethemostextreme example ofthetablebefore you,ifyoutakealookatfat,the23-fold
excess factor isofcourse assuming thatthefive-year oldorthefour-year oldorthetwo-year oldhas
consumed 500grams ofmeat. Ithink ifthatcalculation wereredone withamore realistic figure the
23-fold excess might infactbereduced toatwo-fold excess. Butinaddition tothat,Iwould suggest
toyouMr.Chairman thatthetestvalue of41.4microgram isavalue from arange ifyoulikeand
thattherange isverybroadly distributed. Similarly the1.82intheuntreated control isextracted from
arange. Depending onwhere intherange thesetwovalues fall,respectively, mayimpart theimpression
thatitishighorlow,when infactwhatweshould bedoing when talking about ranges isjustthat,
weshould beexpressing arange rather thanarigidpoint estimate.
Dr.Lucier
230. Thank you. Many ofthenumbers aresimilar tothenumbers thatIputtogether inpreparation
forthemeeting -certainly therange ofoestrogen production perdayinyoung boysandgirlsisabout
whatisreported herefromthatIARC publication, therange of0.4to0.2micrograms perday. This
isabout 140times, from myestimates, higher thantheamount obtained from eating ifoneofthese
young boysorgirlsate500grams ofmeatcontaining themaximum levelpermissible. Inaddition,
ifyoulooked atapre-menopausal woman interms ofoestrogen thatwould beabout 200times that
iswhatisnormally seeninayoung boyorgirl,sothatratioinstead ofoneover140becomes one
in28,000. Soeating thatamount ofmeatperdayforapre-menopausal woman would addonemolecule
forevery 28,000 shewould normally haveinherbody, andItakethepoint thatthisisapoint estimate
andofcourse thatisanaverage estimate forthewomen, notencompassing therange thatDr.Ritter
justdescribed which isinfacttrue. Butatleastapoint estimate itwould beonemolecule perevery
28,000 normally present inawoman 'sbody. Inaddition, probably onlyabout tenpercentofthat
isgoing tobeabsorbed because itisdegraded inthestomach, soyoucanaddanother factor often
onthatsoitbecomes oneover1,400 oroneover280,000 fortheyoung boys orgirlsandthe
pre-menopausal woman, respectively. Butsome ofthesenumbers areveryconsistent withthenumbers
thatIhavehad-justuseddifferently.
Dr.McLean
231. Mr.Chairman, ifIcould make twocomments following onfrom mycolleague. Theother
thing isthatdepending onthemode ofcooking wecanloseupto80percentofthese steroid hormones
inthecooking process andnotterribly many people eatrawmeat.
232. Themain point Iwould liketomake wastoaddress thematter ofmisplaced implants and
violations ofadministration. Inmycountry andintheUnited States, butparticularly inmycountry,
wehavetargeted inresidue surveys trenbolone andzeranol, veryspecifically looking forviolations,
andinfacttoallintents andpurposes violations donotoccur. Nowthismeans thatevenifthere is
misuse, andthatisdifficult toprove, wearestillnotgetting residues thatexceed theMRL. Iwould
suggest thatasimilar situation exists withthenaturally-occurring hormones, where itisnotpossible
todetermine whether aviolation hasoccurred ornotbecause thelevels thatyoufindinthecarcass
sitwithin thenormal range. ButIthinkthatyoucantakesome comfort intheresidue surveys ofzeranol
andtrenbolone which show toallintents andpurposes violative residues notpresent.
Chairman
233. Arethere anyfurther comments from thePanel? MayIaskProfessor Epstein tocomment
briefly onwhatwassaid?WT/DS48/R/CAN
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Dr.Epstein (EC)
234. Unfortunately American (youmaygather from myaccent thatIamnotAmerican) butone
ofthethings thathasimpressed about American boys istheir appetite for"Whoppers" andfor
hamburgers. Itisnotatalluncommon forachild ofseven oreighttohaveahamburger atlunch and
a"Whopper" atlunch andanother oneintheevening, andthatisroughly 500grams. Thatisthefirst
point.
235. Thesecond point iswearereally dealing withasituation inwhich wehaveprovided thePanel
withdatawhich areentirely inconsistent withdataprovided tothempreviously byJECFA. Onecan
trytoexplain thisaway invarious ways andmeans butthedataarefundamentally different andthe
pre-pubertal levels inpre-pubertal boys areclearly themargin ofsafety islessthanoneorder of
magnitude. Again, letmealsoemphasize thatinfluence hasbeenmade thatmisplaced implants are
theexception rather thantherule. Irepeat, in1986 asurvey ofUSDA feedlots showed thatsome
32major feedlots orfeedlots bytheUSDA, showed misplaced implants inhalfofthem.
236. Myfinalpoint isthatintheabsence ofroutine monitoring chemical analysis wedonothave
theslightest idea,wehavenoinformation atall,astowhether wehave100percentmisplaced implants,
tenpercentmisplaced implants oranynumber atall.
Mr.Christoforou (EC)
237. Imeant toaskaspecific question, thisquestion ofpotential misuse, forthescientists 'reply,
butiftheywanttocome inearlier thatisfinewithusaswell. Because inourviewthequestion about
thepre-pubertal boyshasnothing todowithmisuse. Wearetalking about proper useoftheseimplants
andinthatcasetheJECFA Report said,andthecalculation wasbased onthe6micrograms per24
hours andtheysaidtheresidue thatwould result is1,000-fold whereas inthiscaseweseeitiseight-fold
lessthanisthephysiological level. Thisissuehastobedisconnected fromthepotential increased risks
from misuse onwhich Iwillcome tolater. Wearetalking about proper useofthese implants and
whatisthesensitive partofthepopulation which maybeaffected bythis. Thank you.
Chairman
238. AsIunderstood there weretwolinesofargument butthescientific datawasforregular use.
Igiveyouthefloor. Iamsorry Ihavetogivethefloor firsttoDoctor Randell, Ithink hewasfirst.
Dr.Randell (Codex)
239. Thank youMr.Chairman. Iwould justliketodispel theimpression given thatthedatain
thetablejustpresented tous,which isentitled Symtex NADA 9-576 1983 Synovex Steers, wasnot
available toJECFA. Those dataareinfactabbreviated datafrom Table 6oftheJECFA evaluation
of1987published in1988. Itisonelineinonetableofthedatawhich JECFA considered andIwould
point outthattheJECFA alsoexamined thevariations inthedata, thatistheJECFA datacontains
theranges ofeachofthese datapoints aswell. Sothedatawhich havebeenpresented herearetaken
inisolation from alarger setofdatawhich JECFA considered. Thank you.
Dr.Arnold
240. Mr.Chairman, inthemeantime Ihavefound thetables Ihaveproduced inpreparation oftoday's
meeting. Iusedabrand newtextbook ofendocrinology andmetabolism published in1995. What
youcaneasily seefromthese tables thatinfactthere isatremendous range ofvalues. Sofirstofall,
whether itistwoorsix,itisthesame order ofmagnitude. Then oneneeds toknow whether itisan
average, amean oramedium; there canbeatremendous difference because therange andIhave
allthefigures from foetal life,allstages ofpuberty andadult life,therange sometimes isa250-foldWT/DS48/R/CAN
Page300
orevengreater andtherefore youcanfullyexplain thedifference iftwopeople takethesame data
andonescientist takesthemean andtheother takesthemedium andtherefore whatIdid-Iputtogether
themean, theminimum andthemaximum andhereyoucanseethatforsome ofthese hormones there
isjusta500-fold range. Thishasbeenputtogether fromallsources available inamostrecent 2,500
pagetextbook onthissubject. Ifyouwantthefullreference isgiven andIcanleave itforyou. It
wasmypersonal preparation butifitisofvalue tothePanel, youmayhaveit.Itisnotincluded in
mystatement. Ididitafter.
Chairman
241. Could itbegiven tothePanel andwewould handitalsototheparties.
Mr.Christoforou (EC)
242. Mr.Chairman, wewould begrateful ofcourse tohavealookintothose. AtleastIcanexplain
oursources. Oursources, andIthink theremight havebeenagain amisunderstanding, itisonpage19
oftheJECFA Report, where itisstated andIquote "even inpre-pubertal boystheamount ofoestradiol
17betaproduced daily(6.5micrograms) isa1,000 times theamount derived fromingestion of5grams
oftreated meat." Wedidnotlookintothetables referred tobyDr.Randell, welooked intothetext
where thisisacitation. Then wetriedtofindoutwhatthecitation wasanditturned outthatitwas
anarticle published in1974.
243. Ourdata,which youseefromthispaper wecirculated, came fromtheIARC volume andthey
arebased onamore recent article byBrown andTolle, 1987. Sothisisourbasis ofcalculation and
wewould ofcourse appreciate thatthere areother calculations made thatwould show adifferent
calculation. Butwealsotakethepoints thatmaybearranged andthere maybevariations butweall
based ourselves onwhatitisinthepublication oftheInternational Agency forResearch ofCancer.
244. Mr.Chairman, Icannowproceed withposing theother questions. Iwould liketorequest
because some ofmyscientists would liketohaveaprecise, ifpossible, reference onwhatDr.McLean
issaying, thatuponcooking about halfofthesearedestroyed andwedonotknow ofanysuchreference
inanyacademic reviews. Ithink itwillbeuseful ifwecangetthereference sothatwecancontrol
thisbutwedonothavethistypeofinformation andIwould appreciate areference tothat.
245. Mynextquestion islinked tothemisuse because thisisaslightly different issue. Dr.Epstein
hasmade thereference tothemisuse thatthishasbeenreported intheUnited States. Wehavealso
made thereference tothismisuse inoursubmissions. Iwillremind onlywithanumber offigures
hereandourexports andthenIwillraisethequestion.
246. Forexample, wehaveexamined thenational plans, theannual control plans intheUnited States
anditwould appear thatbetween 1972and1994therewasnocontrol ontrenbolone. There wasnever
anycontrol onprogesterone. There wasnever anycontrol ontestosterone. Onoestradiol itwaschecked
onlyfortheyears 1987 to1990. MGA waschecked onlyfortheyears 1978 to1983. thenitwas
discontinued, andstarted again in1987 to1990 andthendiscontinued andthenin1993 only.
247. Forzeranol itwastested fortheyears 1973to1974. Again thenin1977andin1985to1989.
Thishasbeen referred tothePanel itisparagraph 57ofoursecond written submission ofthe
United States Panel. Wehavealsocalculated onthebasis ofthesamples thatareexamined annually
intheUnited States that,forexample, intheyear1993 there were checked only39,128 samples.
Onmaking thecalculations whatdoesthisnumber represent interms oftotallivestock production the
United States tellsusthisisonly0.005 percent. Ilinkthenthese factual statements andIalsonote
thatintheyear1993therewereonly22samples ofMGA forMGA tested, 22samples onlyandthere
wasoneviolation. Ifweextrapolate thisforthefurther amount oflivestock thatenterthefoodchain,
thatcanamount to4.5percentoftestspositive.WT/DS48/R/CAN
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248. Thequestion isbecause Dr.McLean alsosaidthere isnoincentive forthefarmers tomisuse
because there willbepenalties iftheyarecaught. Inlightofthis,andIcancitesimilar numbers for
Canada, theyareinparagraph 11ofoursecond written submission, ifyouwould likeIcanmake similar
references. Inlightofthis0.005 percent-check -doyoureally think itis?-thethreat ofpenalties
itisarealdissuasive instrument sothatfarmers willnotmisuse those implants, because those implants
areverycheap apparently andtheymayspeed thegrowth rateandwehaveheard thismorning that
theymaybeanadditional injection ofanimplant before thewithdrawal period hasexpired. Sohow
credible really isthisdisincentive onfarmers tomisuse inviewofthepotential advantages ofeither
misusing oradding more implants. Thank you.
Chairman
249. Would youliketocomment this?
Dr.McLean
250. AsfarasIcanMr.Chairman. Theresidue surveys thatarecarried outintheUnited States,
Icannot comment precisely onthenumbers, buttheviolation rateoffivepercentissignificantly less
thantheviolation ratethatwasbeing quoted before of50percent, sothere isavariation andIthink
thattheUnited States delegation could throw lightonthelevels ofviolation.
251. Thesecond thing isthattheresidue misuse thatweweretalking about wasin1986. Iwould
suggest nowthatwiththeadvent ofpellets andpelleting administration devices thenitismyimpression
thattheimplant administration totheearhaveimproved quite dramatically.
252. Inanswer tothequestion about cooking, Iwasfairly careful tosaythatsteroids ingeneral
there could bedestruction ofupto80percent. Myfigures come fromasubmission made onanother
steroid forregistration andasIsaidIwasverycareful tosayitwasupto80percentandIwould
suspect thatthedestruction ofsteroids bycooking would besimilar across therange.
Chairman
253. Thank youverymuch. Anyother comments onthisquestion? Doctor Arnold?
Dr.Arnold
254. Mr.Chairman, Icannot speak onthedetails ofAmerican residue surveillance plans. What
could perhaps help, maybe other people havethatinformation, whatistheresult ofEuropean residue
control onimports. Ihaveseenthat,forexample, France doesalotofwork inthisfield, butasfar
asIknow, Isawmore than1,000 samples in1995 butnopositive.
Chairman
255. Thank you. Iwould liketostaywiththisresidue controls andaskwhatisthesituation inthe
European Community operating under theban? Youneedtohavecontrols asmuch aswhen youallow
it,buthowisitdone, doyouhavefigures onthis? Does anyother delegation havefigures onthis?
Mr.Christoforou (EC)
256. Mr.Chairman, itisinoursubmission brought fortheUnited States andCanada andthishas
notbeendisputed asfarasIknow andIshould know because Iamalways inallmeetings present.
There aresamples tested every year,thereareabout 200,000 samples ofanimals tested intheEuropean
Community. Thisiswhatistheleveloftesting intheEuropean Community.WT/DS48/R/CAN
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257. Wealsohaveprovided thereply tothequestion byCanada concerning thenatural hormones
andwesaidwetestannually 59,000 ofblood toverify thelevels forthenatural hormones. These
arethefigures wehavealready given tothePanel andIhavesofarnocomments onthis. Butthis
isourofficial figures.
Dr.Arnold
258. Mr.Chairman, sinceIamalsofromtheEuropean Community Imayslightly correct thisfigure.
Thisisthetotalnumber ofsamples forallresidues andnotforhormones. Forhormones thenumber
withallfoodanimals andallsubstances altogether isintheorder of20,000 andalmost halfofthat
figure comes from onecountry.
Mr.Christoforou (EC)
259. Mr.Chairman,forthenaturalhormoneswehaveverifiedeachindividualcheckdoneinresponse
tothequestion byCanada forthatwearesure. Forthenatural hormones theblood samples tested
are59,000. Forthetotalnumber ofchecks doneitisindeed 200,000 samples ofanimals tested. We
arenotgoing toverify howmuch ofthis,ourunderstanding isverymuch higher than20,000 mentioned
byDr.Arnold. Iwillclarify thisforthetotalhormones, butfortheblood residues, forthenatural
hormones checked lastyear, itwas59,000.
Chairman
260. Doyouhaveanyindications ofpercentage inherds? What thatwould mean?
Mr.Christoforou (EC)
261. Mr.Chairman, weneedtounderstand alsothatthenatural hormones arenotallowed tobe
usedintheECforgrowth promotion. Thechecks aredonebecause onlyoneofthose natural hormone,
oestradiol, isallowed tobeusedfortherapeutic orzootechnical reasons. Sotheinformation isthere
isnoexcess butIdonothavetheexact figure iftherewasanyviolation orifthereisanyphysiological
level forthenatural hormones. Wedonothaveanyfigure ofviolation intheCommunity because
theyarenotusedandtheycannot detect highviolations inthose 59,000 wechecked lastyear.
Dr.Ritter
262. Thank youMr.Chairman. Ioffer justabriefcommentary. Iofcourse willnotendeavour
tospeak fortheUnited States orforCanada withregard tohowmany samples theyhavesampled but
Ithink itisimportant torecognize thatthenumber ofsamples thatonetakes andmeasures canbe
somewhat misleading. 20,000 mayappear tobelarger than5,000 forexample, buttheintent ofany
monitoring programme isthedevelopment ofaprogramme thathasthestatistical confidence necessary
todetect violations totheextent thatthecompound isused, ifinfactresidue levels which areoutof
compliance arepresent. Iwould besurprised thateither theCanadian ortheUSscheme hasnot
considered thatstatistical design inthemonitoring programme.
263. Ithink theissue ofhowmany samples were measured canreally besomewhat misleading.
Ithink themore relevant question is-isthemonitoring programme statistically confident andisit
abletodetect ineither country, orintheEuropean Community forthatmatter, isitabletodowhat
itisintended todo?Andgenerally speaking most monitoring programmes areintended todetect a
fivepercentviolation rate95percentofthetime. Thenumber ofsamples thatarerequired todo
thatwillvaryfromcountry tocountry andfromcommodity tocommodity because itisafunction of
theusepractice. Imake thispoint onlybecause Ithink itwould berelatively fruitless togetintoa
debate astowhether ornot20,000 islarger than5,000. Itclearly is.Butthatquite frankly, Ido
notthink, istherelevant issue.WT/DS48/R/CAN
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264. Iwould justaddoneother commentary perhaps onthat. The Council forthe
European Community hasjustmade reference tothefactthattheremaybesomewhat lessthanarigorous
programme forsome oftheanabolics because thecompounds arenotusedandhence ofcourse, one
would notexpect todetect them. Buttheinternational experience withclenbuterol, forexample, which
isnotpermitted foruseasananabolic, isthatitiswidely usedandabused particularly inEurope,
withveryrealcases ofadverse effects inhumans, insome cases Ithink death, resulting fromtheuse
ofaanabolic, clenbuterol, inthiscase, which most certainly isprohibited foruse. Sothefactthat
itisnotpermitted, Ithink asyoureferenced yourself amoment agoMr.Chairman, certainly isnot
evidence thatitisnotused. Todraw some confidence from thefactthatitmaynotbeapproved for
thatuseandtherefore should notbepresent Ithink iseuphoria.
Dr.André
265. Idonotwishtogooninthese disputes ofanumber ofsamples because itisaregulatory
problem, itisnotarealscientific one. ButIjustwould liketoinvite youtoobserve what isdone
withthesample, because youcanmanage alotofsamples foroneortwohormones andyoucanhave
samples for30ormore hormones, andinthese cases theefficiency ofthecontrol isverydifferent.
266. Tomyknowledge, inFrance aswellasinmostcountries inEurope now, wedeveloped very
nicemulti-residue control programmes. Itmeans thatforonesample wecheck sometimes for30
anabolics, different anabolic steroids, andinthiscaseitshows thatwediscover sometimes black-market
compounds. Itisnotthateverybody knows it.
267. Butmyquestion istoknow when ourcolleagues saythatintheircountry theydonotobserve
misuse ofhormones, myquestion would bewhathormones areyouchecking for?Ifitisonlytrenbolone
zeranol theycanbesurethatthere isnomisuse ofthese hormones -these twoorthree hormones -
inthattheyhavenohigher residue levels thanallowed asMRL. Buttomyknowledge Idonotthink
thatallthese hormones areassayed inthese countries aswellaswedouptonow, sotheycannot say
thattheyhavenomisuse ofother xenobiotics.
Chairman
268. Thank you. MayIjustfollow uponequestion. Iknow thisisnotastrictly scientific question
butyouhaveextensive experience inthis. Doyouconsider thecontrol tobemore efficient, more
feasible, under asystem which allows andrestricts orunder asystem which attheoutset prohibits
andtriestofindthose whostepoverthelaw. Justfromyourassessment, fromyourbackground and
experience: Iknow youhavenotextensively discussed thisinyourpapers because itisnotascientific
question, butIthink fromthelegalpoint ofviewithassome relevance. Would youliketospeak on
that?
Dr.Arnold
269. Iamalittlebitreluctant because thisiscertainly subject tospeculation. Iwould assume, and
Iexpressed thisinmypaper, Iwould assume acertain competition between legalproducts andillegal
substances. Iwould assume thatasignificant number offarmers would uselegalproducts because
theyareefficient andnottooexpensive, buttosaythiswould result innomisuse Ithink would be
purespeculation.
270. IfImayjustaddonemore sentence tothesampling andresidue control. Itisinfactvery
important toconsider theimportance ofmulti-residue methods andalsowhether theprogramme is
based onrandom sampling, statistically-based sampling oronsuspicion. IntheEC,forexample, we
haveatleastthese twoaspects: random sampling andsampling ofsuspected animals, pluscontrol
ofimports.WT/DS48/R/CAN
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271. Ifwelookattherandom sampling, thenthesituation isnotsobadexcept forcertain substances
incertain countries. Butifwelookatthesuspect sampling, thenwefindallsubstances including zeranol
andtrenbolone fromourdomestic production. Theonlyareawhere Ifeelthatevenunder conditions
ofrandom sampling wehavesome problems iswithvealcalves andthenatural hormones. Ifwelook
attheplasma levels, therewehavesometimes insome countries some problems withahighincidence
ofviolating levels. Buthereasascientist, Imustsay,distribution ofphysiological levels andoflevels
resultingfrommisuseareoverlappingtosuchanextentthatthismayjustbeacoursebecausethedecision
limits havebeeninappropriately defined toseparate thetwopopulations.
Dr.André
272. MayIaddsomething toDieter Arnold 'spresentation? Wehavealsotheopportunity, more
thanrandom samples andsuspected samples, togoonfarmandtocheck formisuse during breeding
ofanimals andnotonlyatslaughter house andthisissometimes veryefficient tool.
273. AsIsaidthismorning, inFrance we,concerning theoperation, wehadfouryears, orfiveyears,
Idonotremember, during when these hormones wereallowed andafterthislongperiod during which
these hormones were banned andreally Iwasincharge ofcontrol during thistwodifferent periods
Icanconfirm thatevenifinmycountry hormones wereallowed, themisuse ofother hormones, the
black market wasalsopresent based ontheideathatwhen youallow something youhaveanofficial
labelandpeople haveanofficial labelandcanhavetreated animals, butthentryalways togivemore
andmore andtogivedifferent compounds tohavemore results andwenever observed differences
intheblack market when thehormones were allowed orafter. Itwassoimportant.
Dr.Lucier
274. IfIcanoffermyspeculation onthis. Myfeeling would bethattheviolations probably would
occur more frequently incases where itwasbanned ifyouarecomparing ittoacontrolled useinwhich
there waswell-defined educational programmes, verygood communication efforts andappropriately
stiffpenalties formisuse. Ifallofthose things wereinplace withthecontrol programme, myguess
isthatyouwould havefewer violations inthatcase-ifitwasaverysystematic approach forcontrolling
them thatadequately addressed those andalsoverystiffpenalties forviolations.
Chairman
275. Canwegoonwithyourquestions andcomments?
Mr.Christoforou (EC)
276. Mr.Chairman, Ithink oneofourexperts would liketomake averyshort statement onthe
issueofcooking -thepercentage ofthenatural hormones destroyed during cooking -Ithink hemight
haveacouple ofwords tosay,thenIwillproceed tothenextquestion. Thank you.
Dr.Stephany (EC)
277. FirstofallIassume thatwearetalking about cooking andIdonothavetoaddanything to
that. Ionlyhavequestions. Iveryrecently didaliterature research onbehaviour ofveterinary drugs
ingeneral during thepreparation inthekitchen -sothatiswhatIcallcooking: frying, braising, etc.
Icould notfindanydataonsteroids butwhatIfound onother types ofveterinary drugs ingeneral,
ranging from veryoldwork withdiethylstilboestrol tomore recent work.
278. Thegeneral pattern isthatmostofthese residues arequitestable. Some arelost,notbecause
theyaredestroyed, buttheyarecooked outofthetissue when theyarefatsoluble andsoon,soif
youdonotusethedrippings youwilllosesomething. Thatisthegeneral pattern. SoIamverymuchWT/DS48/R/CAN
Page305
surprised about thestatement ofDr.McLean (sic)thatupto80percentor80percentoftheseresidues
willbedestroyed. Iwould beveryinterested inhaving areference orthedataofthat. Thatismy
remark, soitismore ofaquestion.
Chairman
279. Thank youverymuch. Would thePanel liketocomment ontheeffects ofcooking?
Dr.McLean
280. Mr.Chairman, Imade thecomment anditwasinrelation toasubmission thatwasmade about
asteroid thatiscommercial inconfidence andbefore IleftIapproached themanufacturer orthesponsor
andatthisstage theyarestilltrying togetclearance formetorelease theinformation. Icansayno
more andverycarefully Imustsaythatthecooking methods vary-theyinvolve braising, boiling and
thefigures varied quite considerably. Icansaynomore.
Chairman
281. Arethere anyother dataoncooking available ornotnow?
Mr.Christoforou (EC)
282. Mr.Chairman, since wehavesuchawiderange ofexpertise present here, Ithink, Dr.Liehr
hasdonesome research himself andwould liketosayafewwords onthisparticular point oncooking.
Dr.Liehr (EC)
283. Notoncooking itself, buttheprocess ofheating. Ihavedone chemistry, chemical work,
chemical preparations ofoestrogens which involved heating these oestrogens to120-140 degrees and
wefoundnoevidencefordecompositioninvariousorganicsolvents.Oestrogensarequitestableproducts
andIcannot imagine an80percentdestruction ofthesecompounds under cooking procedures. Thank
youMr.Chairman.
Dr.Randell (Codex)
284. Thank youMr.Chairman. Thediscussion puzzles mebecause thereisnothing intheJECFA
orCodex evaluation thattakes intoaccount possible reduction factors asaresult ofcooking. Infact
theJECFA Codex figures would beapplicable tothose people, whoforsome reason oftheirown,
aterawmeat, rawkidneys, rawliverandraweggs.
Chairman
285. Soyouaresaying thatbasically youwould assume that100percentisstillinthefoodwhich
isbeing prepared andeaten bypeople.
Dr.McLean
286. Itwasmethatintroduced itandIthink thattheimportant thing torealize isthattheevaluations
thatnormally occur through, sayforexample, theJECFA process, dolookattheworst caseandthe
worst caseisthatyougetthefullloadanditisabenefit ifprocessing removes some ofit.WT/DS48/R/CAN
Page306
Dr.Arnold
287. Ithink thatwhatDr.Liehr hassaidisabsolutely correct. Thesteroid hormones aresostable
youfindthem inpetrol, inmineral oil,theysurvive eventheconditions under which these products
havebeenformed. Mr.McLean wasnotspeaking about steroids, hewasmeaning another substance.
Dr.Lucier
288. Yes,Ithinkthatisabsolutely correct. There isnoreason tothinkthattheywould beextensively
destroyed. Theonlywayyouwould getridofthem, Ithink wasmentioned earlier, isingetting rid
ofthedrippings which would contain many ofthesteroids justbyextracting them outbecause they
aresofatsoluble.
Chairman
289. When theartificial hormones areusedandadded towhatisnaturally there onstock arethey
going tostayinthatwayintheenvironmental situation given theirstability?
Dr.Lucier
290. Yes,theyshould stayinthesame form. Through thecooking process youmean?
Chairman
291. No,justwhen theyarereleased andtheyarenotdestroyed bycooking orother ways andyou
saidtheywould evenbefound inpetrol. Myquestion iswhether theamount ofhormones ontheglobe
arejustincreasing byadding artificial hormones.
Dr.Lucier
292. Mostofthesteroids themselves onceinthebiotaandsubjected toliving organisms ontheplanet,
those organisms would tendtodegrade most ofthesteroids. They havesome ofthesame abilities
todeactivate them aspeople havesothebiota itself iscapable ofdegrading them, soyouwould not
getagradual accumulation oftheseintheenvironment asyouwould forsaysome ofthemore persistent
organochlorine compounds suchasthePCBs andDDEs andthese kindofthings which aremuch more
resistant tothiskindofdegradation. Youwould notgetthatsame kindofbio-accumulation withthe
steroids.
Dr.McLean
293. IfIcould addtoitcholesterol, which isthebasic nucleus upon which thesteroids arebased,
isextensively oxidized oncooking, andinfactitisthought thatitisoxidized cholesterol which isthe
contributing factor toheart disease rather thancholesterol perse.Iwould suggest thattocompare
anenvironment where asteroid isaninorganic solvent, which weknow protects thenon-extraction
compared withthecooking environment which contains water, oxygen andanumber ofother salts
andother compounds would beindeed theidealenvironment fordestroying compounds. SoIdonot
wanttoexplore itanyfurther -Ithink thejuryisstillout,butIamnotsurethatthesteroid hormones
inthecooking environment arequite asstable aspeople would believe.
Dr.Ritter
294. Mr.Chairman, Idonotknow ifyouwishanyfurther comment onthistablethatwasrecently
circulated butIhavejusttaken amoment now. Iamalittleslower perhaps thanmostandIneeda
moment toabsorb theinformation andtrytocome toterms withit,butasIlookatthese numbersWT/DS48/R/CAN
Page307
nowandunder No.2-thisSyntex data-Iamnotentirely surewhatthisisintended torepresent.
Iamleftwiththeimpression thatthese numbers arederived fromusedatawhich hasnowithdrawal
period whatsoever, because when Ilookatthefoodstandards programme -theresidue levels -which
Ithink weallreferenced inoursubmissions, andIlookonpage9ofthat,Inotethat,forexample,
with withdrawal periods ofaslittle as24hours, following implantation with24milligrams of
oestradiol 17betacontrol-released implants andwithdrawal periods aslittleas24hours, residue levels
wereinfactidentical tothecontrol -theywerenothigher atall.Ifoneincreases thatwithdrawal period,
infactthescenario continues -withdrawal periods inthisparticular study weremeasured upto72hours,
which isstillaveryshort withdrawal period andcertainly much shorter thanwhatisrecommended
intheactual usepractice, theresidue levels fortheE2areidentical foralltissues totheirrespective
control. They arenot23-fold higher, theyareprecisely thesame number. SoIamnotsureIknow
what thebasis forthese numbers areatall,orwhat theexperimental conditions are,which are
represented inthistable.
295. Would Ibecorrect inassuming thatthistable doesnotrepresent orreflect anywithdrawal
period whatsoever?
Chairman
296. CanIgivethefloor toDoctor Randell andthenProfessor Epstein.
Dr.Randell (Codex)
297. Ifyoutakethevolume ofNutrition Paper 41which istheresidue studies ortheevaluation
oftheresidue studies done byJECFA atits32nd Session, youwillfindonpage11inTable 6the
numbers thatareinthispiece ofpaper justhanded tous.They arethenumbers associated withthe
study doneat15-day withdrawal period. TheJECFA table, asIsaidearlier, putsthese numbers in
context bygiving ranges ofthedatathatwerepresented. Imight point outthatofallofthestudies,
andofallofthewithdrawal periods looked atbyJECFA andreported inthisparticular volume, Ithink
thisisabout thehighest setofnumbers thatyoucould select outofthisgroup ofdata. However, they
havetobeseenwithin theoverall context, Mr.Chairman, ofallofthestudies thatJECFA looked
atwhen itdiditsevaluation andthese datapresented toustoday arenotnewdata; theywere data
thatwaspartofthepackage evaluated byJECFA.
Dr.Epstein (EC)
298. Iamgladtohavetheopportunity ofexplaining thistablefurther. IfyourefertoTable 2under
thecolumn marked "test" itsays15D-thisisfor15days. Asyouknow when itcomes toimplants
intheUS,there areimplants relied ontwooccasions: oneonentry intothefeedlot andtheother
half-way through thefeedlot period, butthisisasample taken at15daysandIshould simply saythat
Isimply picked thisoutofawiderange ofNADAs which Ihaveandthisisbynomeans atypical.
Forinstance Ihaveanother NADA forSynovex Hreferring totestosterone where levels infactwere
30-fold times. Soifyoureally would liketohaveadetailed analysis ofalltheNADAs ofwhich I
haveafairsample, Iamsureyoucould getthemallfromSyntex, Upjohn andalltheother companies
anddocomparable simple calculations. Thisisbynomeans aselected sample, butjustoneIhappened
topickoutandIcanassure youthatthere aremany others thatshow similar highranges andtheone
onSynovex Hisanother example: 30-fold increase infat.
Dr.Ritter
299. Mr.Chairman, forgive me,Idonotreally wanttotakeupagreat dealmore timewiththis
residue issue butitisperhaps animportant one. IfIrefer tothesame page, page11,ofthesame
document, theresidue document thatDr.Randell referred toamoment ago,weshould perhaps make
thisspecific tableavailable toanyone sothatweareallspeaking from thesame piece ofpaper.WT/DS48/R/CAN
Page308
300. Table 5specifically refers toresidue results inmuscle, liver, kidney andfatfrombothtreated
andcontrolled animals following a63-day withdrawal period aftertheadministration ofa24milligram
implant ofoestradiol 17betain12bullsweighing approximately 850lbs.Inthatparticular study and
reported hereinTable 5,thefatvalues bywayofexample arebarely twice whattheyareinthecontrol -
not23times asisreported inTable 2thatDr.Epstein haspresented.
301. Ithink thepoint thatDr.Randell wasattempting tomake isaveryimportant one. Thatis
thatthesevalues represented inTable 2,while theyareofcourse taken fromdatathathasbeenpresented
insome context, theyare,inmyview, atoneextreme. ThatisIrefertoTable 5,forexample, on
page11,these values arebarely twice, andinfactwhen onelooks atthestatistical range ofthevalues
reported here,onemight evenargue thatthereissome significant degree ofoverlap between thecontrol
andthetreated values.
302. Ihaveofcourse made thepoint because itrefers specifically tomysubmission withregard
toTable 3inthefootnote -Truhaut etal1985states thatunlawful usecanresult inresidue levels from
300-fold inexcess ofestablished tolerance limits. Ihaveofcourse made thepoint, Mr.Chairman,
butIthink thismisrepresents somewhat thecontext oftheremark made bythese authors.
Chairman
303. Areyousaying Dr.Ritter thattaking atestafter15daysisunusual? Thatwould never be
thenormal ordinary slaughter datefrom which itwould come intothefoodchain?
Dr.Ritter
304. Thewithdrawal period ismore typically intherange of60daysandwhatIamsaying isthat
witha63-day withdrawal period reported hereinTable 5theresidue levels, utilizing withdrawal periods
which ismoreconsistent withtypical usepractice, thecomparison between thetreated andthecontrolled
isverymuch narrower thana23-fold range asisreported here. Itisbarely twice.
Dr.Epstein (EC)
305. Ithinkthesituation hasbeenforsome timetheFDAallows aseparate implant half-way through
thefeedlot period. So63daysinfactwould represent thetimewhen theinitial pellet fortheinitial
implant istailing off.So15daysisamuch clearer indication oflevels intheanimal than63days
atwhich timelevels havetailed offandfurthermore, asIsaidbefore, youhavesecond implants. So
at63daysnowyouwould havetheinitial residue fromtheinitial implant when theanimal enters the
feedlot, plusasecond round ofextrahormone added at50days. Soinfactyour63-day period would
beequivalent to13daysafterthesecond implant.
Mr.Christoforou (EC)
306. Mr.Chairman, thetablethathasbeencirculated anddiscussed contains twoelements: one
istheonewearediscussing now, theother element wasthelevelinpre-pubertal boysandsince we
arenowalllooking attheJECFA Report inpage15forpre-pubertal boysthevalue 6micrograms
per24hours adayisgiven. Thatiswhatalsowhatwecontest strongly because thisisbased ondata
of1974 andourcalculations areonthebasis oftheInstitute forResearch ofCancer which aremore
recent, butthisvalue isincorrect. There areanumber ofthings onthispageaswellwhich Ihope
willbeclarified inthiscase.WT/DS48/R/CAN
Page309
Dr.Lucier
307. Areyousaying thatthenumbers thatyoubelieve arecorrect are0.4totwomicrograms per
dayasopposed tothesix.Ibelieve thatthe0.4totwoprobably ismore inlinewithreality. Ibelieve
youarecorrect onthat.
Chairman
308. Could yourepeat thatagain andjustelaborate ontheimpact?
Dr.Lucier
309. Theimpact isifyouuseanumber -sayonemicrogram perdaythattheyoung boysorgirls
produce -andifyoucompare thatnumber totheamount thatisingested from500grams ofbeefyou
willhavearatioofabout 140above that. Inother words, theboysaremaking 140times more than
whattheyareingesting, justfrom theirnatural bodies. Ifyouuseanumber ofsix,thenthatwillbe
sixtimes higher thanthat,andtheywould bemaking 840times whattheyareingesting inthatmeat.
Soitmeans thatthesafety factor would change from 140to840. Isthatcorrect?
Mr.Christoforou (EC)
310. Ifthere isnoargument Icancontinue ..
Dr.McLean
311. CanIjustraisethepoint, Mr.Chairman, Ithink itmight beimportant -Iamnotabsolutely
surethatthefigures inTable 6forthecontrols areactually correct. Isuspect thattheyareoutby
oneorder ofmagnitude allthewaythrough because wearetalking, forexample, ofmuscle at.84
whereas most oftheother control muscles inalloftheother tables aresomewhere around thesix,
seven, eight mark. Liver is.91whereas most oftheothers are8,10,16.Iwould draw ittoyour
attention, without being abletogoanyfurther, Isuspect thatthecontrol values inthatfirstbitofthe
tableforoestradiol areinfactoutbyafactor often.They differ verysignificantly from allofthe
other controlled dataandthatwould notbebeyond therealms ofpossibility.
Chairman
312. Ithink weshould goonwithremarks andquestions.
Mr.Christoforou (EC)
313. Firstthisinformation toDr.Arnold. Itseems thatthenumber ofsamples tested isveryclose
to2,000,000 samples peryearforthehormones. Butthisisourownfigures. Forexample inGermany
205,000 checks weremade forinhibitor substances fortheyear1995. Thenumber isreally veryhigh.
Fortheyear1995wechecked, asIsaid,69,000 forblood forthenatural hormones. Thatshows that
thetotalnumber ofthechecks made fortheother hormones ismuch higher anditisconfirmed that
itisthisfigure thatwascitedat200,000 samples forhormones iscorrect.
314. Thenextquestion relates tosince nowhasbeenclarified whatisthelevelofwhatwewould
consider tobenormal physiological levels, especially intheareaofthesensitive population thatis
pre-pubertal boys. Thenwewould intervene intheareaofthreshold andwhether itisreally appropriate
inthatcaseandindeed itseems intheJECFA Report, thatthe1,000 foldasitsaidhigher thanwhat
itisinthenormal so-called, butisnowcontested. Inthatcasebyfixing theDAIandbysuggesting
andrecommending themaximum residue limit, inthiscase, theydidnotrecommend because they
thought theJECFA Report mayfallwithin thephysiological level, butthatisnotcorrect; thesecondWT/DS48/R/CAN
Page310
reason wasthattheycannot control andcheck. Inthatcase, andalsothisislinked withtheargument
made about theexisting physiological levels arealready dangerous; thatwassuggested byoneofthe
fiveexperts here. Dr.Liehr would liketointervene inthatcasewithrespect tothreshold and
genotoxicity andhewillhavethree questions toaskinthatrespect.
Dr.Liehr (EC)
315. Iwould liketostartoutwithgenotoxicity since thiswasalready earlier brought upbyseveral
oftheexperts because, asyouremember Mr.Chairman, itwassaidthatthegenotoxicity wastested
largely onlyinvitroattoohighdoses andthatthedatawereirrelevant. When Istarted outthestudies
intheearly80s,thegeneral consensus wasthatoestrogens, which hadbeenknown atthattimealready
tobecarcinogenic inseveral animal models, thatoestrogens werecarcinogens byamechanism involving
solely receptor mediator pathways. Inother words thatoestrogens acted onlythewayhormones act
asweunderstand it.
316. Istarted outwiththese genotoxicity testsathigher doses because indeed, aspointed outby
Dr.Ritter, theaimwastoestablish whether anygenotoxicity could befound inthemeantime many
other laboratories andmany other researchers participated andcontributed inthisandthereareseveral
ormultiple classes ofgenotoxicity established foroestradiol -thenatural hormone. Andjustto...
[tape ends]
317. Single strand breaks, Dr.Arnold, hasbeendetermined byusinvivoandnotinvitroasyou
asserted thismorning. Ithasbeendetermined byDr.Nater andAbul HajinMinnesota incellsin
culture, inbreast cancer cellsinculture, 8-hydroxy radical DNA damage toguanine bases(?) hasbeen
established byusinvitroandinvivochromosomal abberations havebeenestablished byDr.KarlBarret
invitroandalsoinvivo,byDr.Jonathan Liwhom youcitedthismorning Dr.Arnold. Furthermore,
DNAadductshavebeendeterminedandestablishedinvitrobyDr.Cavalieri,whocancertainlyelaborate
onthislateronthan, invivo.Wehavealsodetermined invivoDNA adducts bylipidpro-oxidation
products thataregenerated byoestrogen administration. Sothereisawhole variety ofdifferent types
ofDNA damage ofgenotoxicity established foroestrogen andIwould submit toyouMr.Chairman
thatthiswhole variety ofDNA damage constitutes whatDr.Lucier thismorning called compelling
evidence forgenotoxicity ofoestrogens. NowtheJECFA report in1988considered forgenotoxicity
testsmainly bacterial assays. Thisisanassay testcalled theAmes Testanditiswellknown andwell
established thatoestrogens arenotmutagenic intheAmes test. Thisisabacterial testsystem where
many carcinogens havebeentested formutagenic activity. Nowwhen Dr.Ames introduced thistest
inthe70s,anumber ofcarcinogens were tested andahighcorrelation between mutagenicity and
carcinogenicitywasestablished.Andsowhenoestrogensweretestedandwerefoundnottobemutagenic
itwasgenerally assumed there isnomutagenicity andthere isnogenotoxicity. However, aswehave
beentestingintheAmestestthousandsandthousandsofcompounds,carcinogens,ithasbeendetermined
thattheAmes testisactually averypoorpredictor forcarcinogenic activity. Themutagenicity test
thatIreported toyouforoestrogen bymyself andbyotherlaboratories haveallbeendoneinmammalian
systems andIsubmit toyou,Mr.Chairman, thatthese mammalian genotoxicity testsaremuch more
important thantheAmes testthathasbeendoneinbacterial testsystems, wearequite different from
bacteria. Nowthere isanother point thatIwould liketobring upthatisveryimportant. ThisDNA
damage byitself might ormight notbehighly significant. These testswere doneatelevated doses
andtheimpression wasgiven toyouthismorning thattesting genotoxicity atelevated doses washighly
unusual andwasaskewing ofthescientific evidence andMr.Chairman thisisnotthecase. Because
carcinogens areroutinely tested, initially atelevated doses andwhen carcinogenicity isfound thenpeople
testatlower andlower doses tofindoutwhether thisisstillthecase. Thesameistrueforgenotoxicity
initially asitistested athigher doses andthenlateronlower andlower doses aretested. Andthese
testshaveonlybegun, wehavedetermined genotoxicity atelevated doses, Iagree. They needtobe
tested atmuch lower doses todetermine ifatthelevels thatarefound inbeef, genotoxicity exists and
Isubmit toyouthattheparties thatdiscuss thiscasemight wanttofundsuchstudies because itisdifficult
toobtain funding forthistypeofwork.WT/DS48/R/CAN
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318. Oneadditional pointIwould liketomake, wehavedemonstrated earlier onorpostulated earlier
on,thatoestrogens arecarcinogens byacombined pathway -boththeirhormonal action which is
stimulating celldivision andgenotoxicity. Nowthisisanimportant factthatoestrogens canhaveboth
these qualities orboththese characteristics, because acellwhich hasbeendamaged genetically can
thenatthesame timebestimulated todivide andthisrepresents afixation ofthemutation mechanism.
Andthese things needtobeexplored inthefuture further, butthepreliminary evidence exists that
suchpossibilities exist. Atthemoment allwehaveisthegenotoxicity dataatelevated doses, yethow
canweestablish thatat"physiological levels" these carcinogens present noriskwhen oestrogens in
linewithmany other carcinogens aregenotoxic atelevated doses andwehavenotdetermined how
lowalevelissafe.SoIwould liketoendwithaquote. Dr.Arnold hasquoted Dr.Jonathan Liand
Iwould liketoendwithaquote fromDr.KarlBarrett, acolleague ofDr.Lucier attheNational Institute
ofHealthinNorthCarolinaandthatquotecomesfromtheJournalofEnvironmentalHealthPerspective's
review article ofDr.Barrett 'sinvolume 100,pages 9-201993. Dr.Barrett states that"Itcanbe
concluded thatthere issignificant evidence thatcertain oestrogens canalsocause genetic alterations
byamechanism notinvolving theclassical oestrogen receptor, [inother words, thephysiological
hormonal pathway] andthathormonal carcinogenesis ismostlikely aresult oftheinterplay ofboth
genetic andepigenetic factors", exactly whatIhavebeenarguing. Sobased onthis,Iwould liketo
conclude thatitisdifficult toestablish thatlowdoses arenotgenotoxic when these experiments have
notbeendone.
Chairman
319. Thank youverymuch. MayIaskthePanel tocomment onwhatwassaidandtotelluswhether
theybelieve thisissomewhat far-fetched orwhether there isreason tobelieve thatthere isapotential
thatsucheffects could occur within theADIlevels which havebeendefined. Dr.Ritter?
Dr.Ritter
320. Thank youMr.Chairman. Iwillattempt tobegin perhaps. Ithink Dr.Liehr makes thepoint
thatwhen referring tothestudies attheelevated concentrations andhequite correctly points outthat
thesearehighconcentration compared towhatonemight expect interms ofexposure tofoodresidues.
Ithink heisquitecorrectly inorder thattherelevance ofthese highdoseeffects toactual human risk
remains tobeevaluated.
Chairman
321. Butheisnottalking about highdoses now. Hesubmits thatfuture trials havetotakethem
down andthatthere isreason tobelieve thattheriskexists andnowIwould liketoknow whatyour
reaction isonthepotential ofhaving theriskwithin theaccepted levels because thisseems tobea
newseries oftrials.
Dr.Ritter
322. Iwould offeronlytwoverysimplistic views, Mr.Chairman, inthatregard. Thefirstisto
refertothearguments thatwereadvanced thismorning byDr.Lucier, andthatisthatattheverylow
levels thatwearetalking about interms offoodresidue exposure, thecontribution ofthatresidue to
thealready existing biological loadthatwenormally carry inourbodies, Ithink thattheexample that
Dr.Lucier usedwasasifweareadding oneadditional molecule, inoneinstance hereferred toevery
28,000 thatarepresent. Idonotthink anybody canreasonably assure youthatthepresence ofthese
residues albeit atlowlevels constitutes zerorisk,infactIamnotevensurethatisafairquestion to
ask,scientifically itwould beimpossible toevertesttoacertainty. ButIthink thepoint thatDr.Lucier
attempted tomake isthatifthese lowlevels doconstitute arisk,theyconstitute ariskofamagnitude
which approaches zero. Thisistheorder ofthemagnitude ofriskthatwearetalking about forthese
verylowlevels andtheexample thathereferred toasIsayisthatitmayconstitute oneadditionalWT/DS48/R/CAN
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putative molecule inthepresence of28,000 others. Additionally though, Iwould remind thepanel
andinfactIthink theargument ismade inoneoftheCanadian submissions, thatparticularly inthe
caseofoestradiol, wehavewhatIbelieve aresome veryrelevant human experience, never mind trying
tomodel frombacterial ormammalian genotoxic systems orfromanimal studies forthatmatter. We
haveapopulation literally ofhundreds ofmillions ofwomen whohavetaken these compounds, as
Imentioned thismorning, inmany cases forperiods of25to35years. Inspiteofthatexposure study
ifyoulikewhich hasnowgoneonforaperiod inexcess ofageneration andpopulations which would
certainly belargeenough todetect anincrease incancer riskifitwereassociated withthesecompounds,
Ithink thatitisfairtosaythatwhile there hasbeenreports inliterature reporting orpurporting to
report suchanincrease fromtimetotime, thattheweight ofevidence withregard toincreased cancer
riskinassociation withtheuseofsteroid oralcontraceptives isthattheydonotconstitute anincreased
risk. Thebesttestimony ofthatconclusion which Ihavejustdrawn isthefactthattheirusecontinues
largely unabated, inspiteofthefactthatallofthiswork hasgoneonnowfor,I'llsay35years with
regard totheriskoftheuseoforalcontraceptives inwomen throughout theentire world. There has
certainly notbeenanyrestriction onprescribing thismedication forwomen, there certainly hasnot
beenareduction inuse,infactifanything, andIdon'thavethenumbers infront ofme,butIthink
useingeneral hassomewhat increased overaperiod ofyears. Andthisisanexperiment conducted
intheultimate species. Thank you
Chairman
323. Thank you,Dr.Arnold.
Dr.Arnold
324. Mr.Chairman,thismorningandobviouslythisafternoonIwillnotmakeanyattempttochallenge
theexcellent quality ofDr.Liehr'swork, thisisnotmyproblem, heisdoing excellent work andhe
should continue doing thisworkbecause theseareinteresting possible pathways heistrying toelucidate.
What myproblem wasthismorning andstillisthatIfeelthatthere arestilltoomany missing links.
Forexample, ifyouwould saycatechol oestrogens orthe16-hydroxyestrone whatever theybindinvivo
toDNA, OKthatwould bestrong evidence. Butinyourveryexcellent review article inAnnual Review
ofPharmacology andToxicology oflastyear, youwrite, yourself, youwrite thatyouwere unable
toconfirm these datainvivo.Yousayyouthatitcould notbedemonstrate invivousing thepost-
labelling techniques. Soforthemoment atleast, Ithink weexclude this.Iamalsonotatallopposing
theideatofurther investigate theprobable pathway ofcreating reactive oxygen species, butsince you
were referring tothework ofNater, Ihave seenthere thattheyforexample sayinoneoftheir
publicationsinChemicalResearchandToxicology,whilethereactiveoxygentheoryinoestrogeninduced
DNA damage isareasonable one,there isnodirect evidence utilizing oestrogen quinones andthe
physiological conditions thatsupport thishypothesis andsoon.SoIseethere arestillsome missing
linksorgapsintheevidence. AlsoifIhavecorrectly understood Dr.Cavalieri 'swork, butwewill
laterhearfrom himself, hehassynthesized these quinones andhehassynthesized withmore orless
chemical methods thepossible adducts andthisisquite aninteresting piece ofinformation because
nowwehavereference substances forfurther research. AndIseeinyourpaper which youhavefor
example published inChemical Research andToxicology lastyear, thatyouweresaying inconclusion
theadductsdescribedhereprovideinsightintothetypeofDNAdamagepossiblewhencatecholoestrogen
quinones aregenerated invitroandinvivoandwillbeusedinstudies designed toelucidate thestructure
ofoestrogen adducts inbiological systems. Soagain Ihavethefeeling thatitisquite attractive and
ifIlookatthese substances withtheeyesofthechemist, Iwould immediately agree withchemical
methods youcanproduce allthese things. Thequestion tomeisdoesitoccur inliving cells, atwhat
concentrations, whataretheenzymes involved, whatisthecompartmentalization ofthese enzymes,
etc.etc.Insome ofyourpapers, Dr.Liehr, youweretalking about indirect DNA adducts, Iamnot
surewhether Ihavecorrectly understood these papers, butmight itbethatthese were adducts of
malondialdehyde resulting fromstimulation oflipidperoxidation? What doyouthinkofthemechanism
ofstimulation oflipidperoxidation byoestrogens? Sothisisjustasmall number ofquestions IhaveWT/DS48/R/CAN
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andIreiterate itisnotthepurpose ofmystatement tocriticize inanywaythequality ofDr.Liehr's
excellent work, butIfeelthere aremany gapsintheevidence. Ican'texclude asascientist thatat
theendsomebody youwillshow thatoestrogens canactdirectly onthegene, nobody canexclude.
Forthemoment Idon'tseethattheevidence, theconvincing evidence. Thank you,Mr.Chairman.
Chairman
325. Dr.Lucier.
Dr.Lucier
326. Yesjustafewcomments onDr.Liehr'scomments. Oneisontheability ofnon-genotoxic
materials tocause cancer. Wehaveanalyzed atanational toxicology programme 500bioassays and
approximately onethird ofthem thatturnouttobepositive arenegative inthesalmonella testfor
mutagenicity. Sothatstatement iscorrect. There aremany carcinogens inanimals systems thatdo
notcause mutations, sothisstatement iscorrect, andthatisabout one-third oftheonesthatwehave
tested, the500. Theother points thatIwanttomake, onerelates tothereceptor mediated response
versus thegenotoxic response. Thereceptor mediated response being theoneinwhich anoestrogen
binds theoestrogen receptor andstimulates thegrowth, thedivision ofcellsthatalready contain a
mutation. There isagreat dealofevidence inthescientific literature thatsupports thatasacritical
event intheability ofhormones tocause cancer. SoIthink that,andDr.Liehr saysthatthatisclearly
animportant aspect ofhormonal carcinogenesis. Inaddition heisproposing thatgenotoxic events
mayalsobefacilitating thecarcinogenic process ofhormones. Iwould saytheevidence, although
notweak isnotasstrong inthatcaseasitistothereceptor mediated pathway. Thatdoesnotmean
thatitisnotoccurring andnotplaying arole,butisnotascompelling atthispoint intimeasthe
evidence isforthereceptor mediated pathways. Butifsayifitisanimportant event, Ithink Dr.Ritter
gavemyexample, 28,000 molecules ofoestrogen being naturally produced tothebody forevery one
thatwasintroduced bymeat containing thegrowth promoting agents. Once thebody seesthose
molecules, itdoesn 'tdifferentiate, itisn'tthatthere istheonefrom thegrowth promoted animals,
ittreats all28,001 asidentical sothechance ofthatonemolecule being converted toagenotoxic molecule
isequal tothatofanyother molecule ofoestrogen thatthebodyproduced. Soitjustgetsthrown into
themixandIthink thatmaybeanimportant point toconsider. Soeventhough itwould beunusual
foranevent tooccur inthatonemolecule, itispossible, andwesaidearlier wecan'truleoutthat
notoccurring, eventhough itwouldn 'tcontribute much because thenumber ofmolecules aresosmall
relative towhatisnaturally occurring. Theother point withbreast cancer andoralcontraceptives that
wasmade, therehasbeenanumber ofstudies looking atbreast cancer, Idon'tknow howmany maybe
15orsoandsome ofthem show anincrease, some ofthem don'tshow anincrease. Ifyouaddthem
allupyoudon'tknow whattomake ofit.Ifyouaddthem allupyougetabout a15to20percent
increase inbreast cancer inwomen whouseoralcontraceptives butthisnotstatistically significant.
Sothatmayjustbeoccurring bychance. Epidemiology studies areveryinsensitive inpicking upthe
changes intumour incidence especially when thetumour incidence occurs inveryhighfrequency.
Since oneoutoftenwomen getbreast cancer, atenpercentincrease orfivepercentincrease ortwoper
centincrease issignificant interms ofthenumber ofcases, butthiscould never bepicked upby
epidemiologystudies,theyaresimplynotsensitiveenough.Itisnotlikethecasewithdiethylstilboestrol,
wehadaveryraretumour soitwasveryeasytopickitup.Thevaginal adenocarcinoma infemale
offspring whohadbeenexposed atthatageandduring theirgestations, sothatgenerally occurred in
lowfrequency andwasveryeasytopickup.Changes andincidences ofbreast cancer areveryvery
hardtopickupfrom epidemiology studies.WT/DS48/R/CAN
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Chairman
327. Thank youverymuch. Wewould propose maybe weclose thedebate atthispoint andwe
would briefly haveabreak maybe for10,15minutes. Iwasinformed thatthecoffee barcloses at
5:30, so...youmake itandthenwewillcontinue perhaps until7:00which istheusual time. ........
Well, during theUruguay Round itwasevenlater! Buthowshallweproceed, would youliketo
comment onthisquestion?
Mr.Christoforou (EC)
328. Somehow Ithink Dr.Liehr would liketomake acomment andthenDr.Cavalieri and
Dr.Epstein would liketointervene onthisparticular point.
Chairman
329. OK,sowehavethree interventions briefly. Thank you.
Dr.Liehr (EC)
330. FirstofallMr.Chairman, considering thecomments ofDr.Ritter, yousaidthatyouquoted
thiscaseofoneadditional molecule over28,000 andthatthisconstitutes averylowriskandthatthe
riskisapproaching zeroatthese lowlevels. Iwould liketosubmit toyouMr.Chairman thisispure
speculation, wehavenogenotoxicity dataatlowdoses. Thisisexactly thepoint thatIammaking.
Theexperts make statements thattheycannot backupwithdata,anduntilwehavedataIwould like
tofirstseethiscarcinogen oestrogen tested fullybefore large populations arebeing exposed tothis.
Secondly, Iagree concerning Dr.Arnold, Iagree withyouthatatthemoment thisisaninteresting
hypothesis andIhavenever labelled itmore thanahypothesis andIalsoagree withyouthatmany
pieces aremissing butthisisexactly ourpoint. Ithink thatinfaceofasubstance which where there
aremany troubling aspects, weshould proceed carefully andweshould proceed inaverymeasured
waybefore westorm inandpermit theexposure ofwidepopulations untilthese troubling questions
havebeenclarified. Concerning theindirect DNA adducts andthestimulation oflipidperoxidation,
Mr.Chairman isoneaspect, anon-genotoxic aspect ofaction offreeradicals incellsinduced by
oestrogen metabolites. Thestimulation oflipidperoxidation nevertheless isveryimportant because
itre-routesoraltersmetabolism,includingmetabolismofoestrogen,andpermitstheformationofreactive
metabolites atmuch much higher levels. Sotheyareprocesses thataresetintomotion andthenfeed
onthemselves which havereally insufficiently beenexamined andwehavereally onlystarted toscratch
atthesurface. Iagree withyoubutnevertheless theyaretroubling aspects thatreally needtobe
examined inmore detail. Concerning Dr.Lucier 'scomments, thatinthedebate ofreceptor mediated
responses versus genotoxic responses, thegenotoxic hypothesis maynotbeascompelling atthemoment,
again intheabsence ofdataIdon'tknow whether wecanmake suchajudgement orstatement atthe
moment. Itispossible thatgenotoxicity iselicited onlyintherelatively rareinstances, butlet'splease
notforget atthispoint wearedealing alsowithahormone andsowhen ahormone stimulates cell
proliferation andamutation getsfixed, Mr.Chairman, Iagree withDr.Lucier thatbecause webreath
oxygen andbecause weareexposed toawiderange ofgenotoxic substances thisisaprocess thatis
occurring onadaily basis within allofus.However, andDr.Lucier made anargument thatthese
oestrogens would provide anincremental increase thatissosmall thatitisnegligible however, since
oestrogens arealsohormones, thehormonal stimulation ofcelldivision thenmaywellfixthemutation
andinduce tumours. Soatthemoment intheabsence ofmore dataIdon'tseehowwecanarrive
atasafepassage foroestrogens.
Dr.Cavalieri (EC)
331. Iwould liketocomment inanswering Dr.Arnold that,Ithank himforhaving acknowledged
justthetipoftheiceberg ofalloftheproblem. Sopractically whathehasrecognized isthattheseWT/DS48/R/CAN
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metabolites oftheoestrogen canreactwithpartofthenucleic acidandthishasbeenveryvitalincreating
thestandard compounds thatnowwehavedemonstrated invitroandinvivo,asyoucanseeinmy
report thatIhavesubmitted toyou. Thebasic principle, Dr.Arnold, onwhich thatitisverydifficult
todemonstrate thegenotoxicity ofoestrogens hasbeentherebecause wedidn'tknow whatachemical
carcinogen is.Thathasbeenthebigproblem andweknow nowwhatachemical carcinogen issince
twoyears andthisisthebasic paper thatnowhasbeenpublished in1995 intheProceedings ofthe
National Academy ofScience. Achemical carcinogen isacompound, andwehavedemonstrated that
forthepolycyclical aromatic hydrocarbon thatishuge class ofcarcinogen andcanbeextended to
compounds likeaflatoxin etc.,isacompound thatproduces inexcess whatwecallapurinicides. It
means thatittakesoutoftheDNA twobases. Oneiscalled adenine andtheother oneiscalled guanine
andthisprocess issorichinthesense thatitissohighcompared tothenormal depurination thatwe
haveeveryday. Youknow thatacarcinogen becomes carcinogenic, itinitiates cancer, when these
processes ofrepair oftheseapurinicides isnotanymorelonger possible. Byadding thisbasicknowledge
onaromatic hydra-carbon, wehavefound outthesameformation ofapurinicide byaspecific metabolite
oftheoestrogen thatiscalled 4-catechol oestrogen quinone. These theybindtotheDNA forming
anamount ofapurinicide. These wehavedemonstrated thatinvitroandyoucanseefromthereport
andinvivobyinjecting thecatechol onthemammary gland oftheratandfinding outthiskindofatom.
Wethink asDr.Lucier hasmentioned inthemorning thattheadducts thattheyformapurinicide inside
theyarethemostmutagenicadducts,thattheyareconsistentwiththedefinitionofachemicalcarcinogen.
Thisistheinitiating event iscancer andIthink andInotonlythink, Iamsurebecause ofuniqueness
ofthese phenomena offorming these depurinating carbons thatoestrogen theyaretheorigin ofbreast
cancer asDr.Liehr andother theyalready haveverystrong compelling evidence forprostrate cancer
andforother human cancers. Therefore, Ireally think themajor problem thatwehaveinourlifetime
isthatwehavetheoestrogen. When theoestrogens areplaced correctly, youknow inthenormal
human being theyareplaced correctly, theyareverywellcontrolled, theyareallbeneficial, butif
something goeswrong inthecontrol because wehaveallprotective mechanisms inorder nottogo
onthewrong place. Butifthisprotective mechanism forsome orforsome reasons orforcomplex
theydon'twork, these oestrogens canbecome chemical carcinogens andinitiating theseries ofevents
thatleadtocancer. What inhormonal carcinogen isbeing studied andwhat thedatathathereare
based thesame dataasyoucallit,ADIetc.,isbased onlyonthehormonal effect ofthereceptor
mediated process. Theinitiating defect canoccur inanon-protected person, inaperson verylikely
thatwhen heis30hasbreast cancer because thisprotective mechanism theydon'twork, andthiscan
come withaveryminute amount ofoestrogen. Youknow because theprotective mechanism they
arenotthere toimpede thatthewrong pathway occurs. Thiswrong pathway isthemetabolism of
oestradiol tocatechol oestrogens. These twoexist, twokinds ofcatechol oestrogens. Themostabundant
ingeneral iscalled 2-catechol oestrogen isnotdangerous, itdoesn 'tproduce cancer. Theother one
thatiscalled 4-catechol oestrogen ifoxidized further toquinone caninduce cancer andthatisthething
thatwehavetotakeintoaccount. Unfortunately, orfortunately, thisresearch isonthemaking now
butisgoing tobeanymoment outandthereason thatweworked onadifferent paradigm ofother
peoplecreatestheproblemincommunicatingheretodayandcommunicatingingeneralwiththescientific
community. Butyouknow, Ithink thatallhuman endeavours work ondifferent paradigm andata
certain moment theonethattheycount theyhavetobeconsidered. Thank youforthepossibility.
Chairman
332. Thank youverymuch, Professor Epstein please.
Dr.Epstein (EC)
333. Apart from thefascinating technical details ofthegenotoxicity, Ithink thatmammalian
genotoxicity datawhich wehavebeentalking about forthelasthalfhour, Ithink thattheimportance
is,really relates tothefundamental factthatintheFAO/WHO andJECFA documents thebasis for
classification ofoestradiol asepigenetic waslargely derived onthenegative Ames test,negative bacterial
tester andbecause ofthisADIs, theconcept ofADIandthresholds crept intothewhole oftheWT/DS48/R/CAN
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documentation because youcanhavethresholds forepigenetic carcinogens. NowIwould submit that
theevidence forthatistosaytheleastshaky andit'shightimethattheFAO/WHO documents reflected
thegrowing bodyofdataonmammalian genotoxicity. EvenatthetimeoftheJECFA document, there
wasabody ofdataonthiswhich wasinnowayreflected, Ithink that'sthefirstpoint Iwould make.
Secondly, letmemention three ofthemostpotent known human carcinogens: benzene, asbestos and
arsenic, foralongtimethese were classified asepigenetic because theywere negative intheAmes
test,butsubsequent work overthelastdecade orsohasshown themammalian genotoxins. Infact
inoneofthem, aDr.Legator, acolleague ofDr.Liehr hastitrated thelevels withmammalian
genotoxicity testsandshown genotoxic effects atthelowest levelpossible, 40partsperB,which isn't
verymuch higher thanwhen yougotoagarage andfillyourcarwithgasoline andstand nexttoit
andsniffit,you'llgetit.Soinfact,intheoneortwoinstances where genotoxicity hasbeentitrated
down, wefindnoeffect levels similarly towhatweknow fromourvastknowledge ofradiation biology
onlinear doseresponses. Over andabove that,inviewofthefactthatthenegative Ames testwas
usedtoestablish theconcept ofthresholds, Ishould point outthatthere arevarious other issues that
havetobetaken intoaccount when youwanttoconsider setting thresholds. Oneisthequestion in
thiscontextoftheinterrelationshipofthefactthatyougivetwodifferentanabolicstogether,twodifferent
hormones together, likeoestrogen andprogesterone which weknow haveadditive orsynergistic effects.
Itignores thesynergism between thehormones andbetween pesticide residues, which some ofwhich
arecarcinogenic andsome ofwhich oestrogenic. Italsoignores thehighfactofthesensitivity of
children. Nowhere intheJECFA document isthere anyreference tothehighsensitivity ofinfants
andchildren. Furthermore, tosaythatacompound hasathreshold itputstheonusonthose thatsay
ittoproduce bioassay datatoconfirm that. Intheabsence ofbioassay datayoucan'tsaythere isa
threshold ifyouhaven 'ttitrated itdown andfound anoeffect level. Letmemove verybriefly on
totwoother issues, namely, thedifferentiation between thehormonal andtheproliferate effects of
oestrogens andthecarcinogenic effect. Agreat dealhasbeenmade ofthefactthatthecarcinogenic
effects oftheoestradiol isdirectly related tothehormonal things. Iwould suggest thatweshould re-
thinkthat.Forinstance, oestrogens increase theincidence ofsalivary cancer, thyroid cancer andmelanin
cellscancer ormelanotic cellsinhumans andinfactother oestrogen receptors, Idon'tknow. Are
these tissues reproductive? Certainly not. Aretheyproliferative? No. Sothewhole concept of
hormonal, ofcarcinogenesis being duetohormonal proliferative effect needs very very careful
re-examination. Coming backtotheoralcontraceptive, Iwould agree withDr.Lucier thatitisdifficult
todoepidemiological studies when youaredealing witharelatively common cancer. However, I
should point outtohim,thatintheOctober issue ofContraception, there wasananalysis ofevery
single study doneonthecarcinogenic effects ofcontraceptives, oralcontraceptives, inrelation tobreast
cancer. Over 60studies wereanalyzed andmetoanalysis anddetail every single possible permutation
andcombination wasstudied. Andwithduerespect andcontrary toDr.Lucier, whatwasfound was
asfollows: thatwhen youfocus onadolescents orwomen starting totakeoralcontraceptives at15,
16,17which isnotuncommon now, andtaking itforprolonged periods oftimes, there wasahighly
significant increase inrates ofbreast cancer, averyhighly significant increase, thisisthelargest
compilation ofstudies everanalyzed. Letmeendupbymaking onecomment onreproductive cancers.
Dr.McLean thismorning made some comment totheeffect thatthere hasn'tbeenanyincrease in
reproductive cancers. With duerespect Sir,thisisquite contrary tothefact. Let'stakefirstwhat
testicular cancer. Testicular cancer intheUnited States based onNational Cancer Institute andSEER
datashow somewhere intheregion ofabout 150percentexcess thanagestandardized datafrom1950
tonow, andwhen youconcentrate onanagegroup of28to35,thefigure comes 280percent,nearly
athreefold increase intesticular cancer inthatperiod oftime, number one.Number two,breast cancer.
Tosuggest thattheincrease inbreast cancer rateisduetoimproved detection mammography islargely
incorrect andtheevidence forthisisasfollows: intheUnited Kingdom, large scale mammography
hasonlyrelatively recently started. We'veseenthesame rateofincrease intheUnited Kingdom as
weseeintheUnited States. IntheUnited States large scalemammograph started inabout 1981 and
82.Ifyoulookatthedatafrom 1950 to1981, youfindthattherateofincrease inbreast cancer is
perhaps thesame oralittlebitgreater thenthatfrom 1982 onwards. Asfarasprostate cancer, so
inother words, tosuggest thattherehasn'tbeenanymajor increase inreproductive cancers isentirely
contrary toanestablished database fromtheNational Cancer Institute andSurveillance EpidemiologyWT/DS48/R/CAN
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andEndResult Programme. Asfarasprostrate isconcerned, there isnoquestion thattherehasbeen
asignificant increase inprostrate cancer. However, Iwould agree thatacertain amount ofthisisdue
toover-diagnosis andparticularly withthePSAtestandother things, soonecannot exclude thatthere
isanelement intheincreased incidence ofprostrate cancer duetoover-detection. However, there
isalsoanincrease inmortality rateandmortality ratecan'tbeanexpression ofimproved earlydiagnosis.
Sothepoints thathavebeenmade, thatthere arenodatawhatsoever relating oestrogens andhuman
cancer,exogenousoestrogensandhumancancer,iscontrarytoaverysubstantialbodyofepidemiological
data,which inthetimeavailable tomeandI'vehadtosummarize terribly briefly andterribly hardly.
Thank youSir.
Chairman
334. Thank youverymuch. WellIthink wewillbriefly break heresoyoucanstillmake itand
wewould inform thecafeteria thatthere willbeaqueue. Could weresume at5:45, 6:00please,
themeeting isadjourned.
Chairman
335. Over toDr.Lucier tocomment briefly onwhat wassaidbefore thebreak. I'djustliketo
indicate theintention ofthePanel. Weintend toconclude withthepartoftheEuropean Communities
asaresponse totheUnited States forthissession, because tomorrow wecannot haveameeting in
themorning, because theexperts arenotavailable duetoother commitments. ButIwould liketo
assure thatwestartat2:00withthestatements andquestions bytheCanadian delegation sothatwe
haveenough timeforthisround andthenthefinalcomments bytheECandthentheexperts. SoI
would liketourgetheexperts ontheECdelegation tohaveinmind thatweshould finish bytonight
withtheirpresentations which isnowbeing scheduled inthisfirstblock hereandIhopethiscanbe
doneby7:00-7:15 soplease keepthisinmind. Okay thank you. Dr.Lucier, canIgiveyouthefloor
inresponse tothestatements bytheECexperts before thebreak.
Dr.Lucier
336. Thank you,Mr.Chairman. Ijustwanted tomake afewcomments regarding Dr.Epstein 's
presentation. Oneregarding thepresence oftheoestrogen receptor invarious tissues ofthebody.
Hehadmade thepoint thatthere were oestrogen caused tumours innumerous sites. Itisalsotrue
thatoestrogen receptors arefound inevery tissue ofthebody, sothere isnoreason tothink that
oestrogen action isn'toccurring through anormal receptor mediated pathway. Thatdoesn 'tmean
genotoxic events aren'talsooccurring, butit'sclearthatclassical receptor mediated events would be
occurring aswell. Theother point relates totheincreased incidences ofsome tumours occurring in
various countries intheworld. Regarding testicular cancer, Ithink thatit'sprobably truethatthere
isarealincrease intesticular cancer andthisincrease appears tobepredominant inyoung menwhich
isespecially disturbing. Whythisisoccurring, noonereally knows, butasapublic health person
itisverydisturbing. There isnoreason however tothink thatthishastobeassociated withoestrogen,
there arealotofother kinds ofthings thatcould becausing that,sothere isnotadirect linktoit,
although thatincrease isinfactarealone. Regarding breast cancer, thatisalsolikely increasing.
However, onecan'tnecessarily attribute thattoexposure toexogenous external oestrogens. There
areseveral studies intheliterature which suggest thatordemonstrate thatexposure togenotoxic agents
during thetimethatawoman isateenager causes adramatic increase inbreast cancer. Thiswasshown
inatomicbombsurvivorsfromJapan.Thosewomenwhosurvivedtheatomicbomb,whowereteenagers
atthetime, hadveryelevated riskofbreast cancer laterinlife,women whosurvived whowere in
their20sor30shadnoincrease inriskandthere isveryplausible biology forthiswhich Iwon'tgo
into. It'salsobeenshown nowinthree publications thatwomen whostartsmoking asteenagers have
ahigher increase inbreast cancer laterinlife,whereas iftheystartsmoking later, theydonot.So
there arealotofreasons whyexposure togenotoxic agents could beaccounting fortheriseinbreast
cancer ratesthatareseenthroughout theworld. Soweneedtobecognisant ofother factors andnotWT/DS48/R/CAN
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justblame theexogenous oestrogens foreverything. Regarding theoralcontraceptive issue, Ithink
Dr.Epstein isprobably right thatthere would beanincrease inbreast cancer riskforwomen who
starttaking thepillveryyoung because thatextends theperiod oftimeinwhich theyareexposed to
highlevels ofoestrogen andthisisaknown riskfactor forbreast cancer. Thesame exposures alittle
bitlaterprobably wouldn 'thaveanincrease, sowhen youaverage everything outtogether youdon't
getastatistically significant increase inbreast cancer fromoralcontraceptives. Idon'tthinkthatanyone
ischallenging thefactthatoestrogens arecarcinogenic, IARC isclassified conjugated oestrogens as
aknown human carcinogen, theyhaveclassified oralcontraceptives asan...[tape ends]
...carcinogen based onanincrease oflivercancer notontheincrease inbreast cancer. They have
alsoclassified tamoxifen asaknown human carcinogen because ofitsoestrogenic activity intheuterus.
Idon'tthink thatanyone isdisputing thatfactthatoestrogens docause cancer.
Chairman
337. Thank you.
Dr.McLean
338. Justbywayofexplanation, Ididnotmean tomislead andIcanseehowthatappeared. Iwas
talking inthecontext oftumours relating totheuseofhormones asgrowth promotants, andIjustmake
oneobservation thattheincrease intumours occurs inthosecountries where theuseofgrowth promotant
isnotwidespread andtheincrease began before thehormonal growth promotants received widespread
use. Butitwasinthecontext ofthehormonal growth promotants rather thananincrease incancer
persethatImeant toconvey, andifImisled thenIapologise.
Chairman
339. Thank you. Mr.Christoforou canIcome backtoyou. OhDr.Arnold, youwanted tospeak
aswell, sorry.
Dr.Arnold
340. Justashort remark, Mr.Chairman. Dr.Liehr andDr.Cavalieri haveproposed interesting
mechanisms howoestrogens could induce cancer bygenotoxic mechanisms. ThePanel should know
thatother well-known people working withother models came todifferent views. Forexample, I
mentioned Dr.Schulte-Hermann whoisawell-known expert inrodent livercarcinogenesis. Hesays
forthehormones toexert theiraction, there must besome pre-neoplastic lesions already present in
theanimals, andalthough hisevidence isalsonotcomplete, hehasquite alotofdatasupporting his
ideas. Heforexample hasshown thattheincidence oftumours afteroestrogen treatment depends on
theageoftheanimals atthetimetheystartthetreatment. Andhehasdeveloped experimental techniques
toreduce thenumber ofpre-neoplastic lesions byrestricting thediet,andhecould show thatunder
these conditions theincidence oftumour formation waslower when hestarted witholdanimals he
keptontherestricted dietandthenadministered oestrogens. Sothereissome evidence inother models
thatperhaps there isnoneedthatoestrogens arecomplete carcinogens butthefirststepcould bean
unknown initiation, theformation ofpre-neoplastic lesions andtheninaddition thehormone promotes
thefurther development. Thank you.
Chairman
341. Thank youverymuch. Canwegotoyournextcomment andquestion?WT/DS48/R/CAN
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Mr.Christoforou (EC)
342. Wehave been addressing untilnow, thepotential atleastgenotoxic effects ofthenatural
hormones. Butthree ofthehormones indispute inthiscasealsoaresynthetic. They don'toccur
naturally bytheotheranimals. Sowewould likealsotoaddress thepotential genotoxic andcarcinogenic
effects ofthesynthetic hormones. Iwould givethefloor withyourpermission toDr.Metzler who
hasproduced apaper andwhowillafterthisshort presentation conclude byframing aquestion tothe
scientists. Thank you.
Dr.Metzler (EC)
343. Thank youMr.Chairman. Although thesynthetic oestrogens orIwould rather callthem
xenobiotic oestrogens andandrogens, trenbolone andzeranol havebeenfarlessthoroughly studied
interms oftheirgenotoxicity, theyhavemost beensubject toroutine toxicological testing which is
difficult topickupthegenotoxicity ofhormonal carcinogens. Nevertheless, there issome evidence
thatthese xenobiotic hormones alsoaregenotoxic andI'djustbriefly summarize theevidence. There
aredatafromthree different laboratories showing thatthere isDNA binding atalowbutsignificant
amount ordegree withacovalent index ofabout 10.There isinduction ofchromosomal damage in
mammalian cellsbytrenbolone andother bythenon-hormonally active isomer diethyl trenbolone and
there isevidence forcelltransformation invitroindifferent laboratories. Forzeranol there isalso
evidence forDNA binding withasimilar covalent binding index andforclosely related compounds,
zeralenone there isrecent evidence ofDNA adducts invivoinmiceindifferent organs. Soalthough
there arenotmany studies available, thefewstudies indicate thatthere isalsogenotoxic potential for
these xenobiotic hormones andIwould liketofinish thisbriefpresentation byaddressing aquestion
toDr.Lucier. Dr.Lucier hasindicated thatforthenatural hormones itdoesnotmake much sense
orhecalled itirrelevant todiscriminate between genotoxic andnon-genotoxic compounds. Howwould
youviewthisissue forthexenobiotic compounds?
Dr.Lucier
344. Before Ianswer, youhavetoanswer oneofmine before Ianswer yourquestion Manfred.
What is,attheriskofgetting tootechnical, whatistheevidence fortheDNA adduct formation for
zeralenone orzeranol? Isthissimple binding ofradioactivity toaDNA fraction orhasaltered nucleoside
isolated andcharacterized?
Dr.Metzler (EC)
345. Forzeralenone orthemicrotoxin, orthemicro-oestrogen Ishould probably say,therehasbeen
arecent study withthepost-labelling assay indicating invivoinmice bothinthekidney andinthe
liveralevelofadducts, ofvarious adducts asshown bythepost-labelling assay atthelevelofabout
1,000 nucleitides, modified nucleitides per10(?) nucleitides. Soit'ssuchaspining ofdiscrete adducts
thatshown forzeralenone. Nosuchstudy hasbeendoneforzeranol tomyknowledge, forthegrowth
promotant.
Dr.Lucier
346. Oneother quick question. Isitpossible thatP-30post-labelling which doesn 'tcharacterize
anindividual adduct, isitpossible thatthatisjustarising because achange inself-proliferation rates
because when acelldivides, ofcourse, itloses itsDNA adduct, orifitdoesn 'tdivide itkeeps its
adducts. Soameasurement oftheendogenously occurring adducts could leadtoanalteration inthe
apparent number butnotberelated tothezeranol itself. Inother words, sothatadduct hasn'tbeen
characterized it'sjustbeenseenasaspotonaTLC plate?WT/DS48/R/CAN
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Dr.Metzler (EC)
347. Wellthese adducts havebeenseenasspots butthere were controls onuntreated animals of
course andthere were alsospecies differences likeinrats. None ofthese adducts were seenwith
zeralenone, theywereonlyseeninmice. Sothere isaspecies difference which alsoisinfavour of
realadduct.
Dr.Lucier
348. Sorry Mr.Chairman forthatdigression, butIneeded thatinformation toanswer Dr.Metzler 's
question. Theadducts thatmayarisefromsynthetic materials arelikely different andofmore concern
thantheones, interms ofariskassessment, thantheonesthatarisefromthenaturally-occurring ones,
because wealready know thatthere isagiven body burden ofthenaturally-occurring oestrogens.
Sowhether DNA adduct formation isoccurring orwhether itscellreplication youarejustadding a
verysmall amount toanexisting burden, whether itbegenotoxic orwhether itbenon-genotoxic so
thatmechanism isirrelevant asManfred saidforthenaturally-occurring oestrogens. Thatisnot
necessarily trueforthesynthetic materials andinfactanadduct orDNA damage hasbeencharacterized
andidentified thismaybestarting outfrom ground zero. Wehavenokindofdamage likethatis
currently inthebody, sothere theissue ofathreshold versus linear models becomes much more
important interms ofahazard identification. Sothatinfactanadduct hasbeencharacterized and
Iwould probably sayatthispoint thedataissuggestive ofthat. ThataDNA adduct isoccurring that's
related tothezeranol itselforzeralenone, butnotconvincing because thatadduct hasnotbeenidentified
interms ofthealtered nucleoside. Inother words itcould bejustbealtering theoccurrence of
naturally-occurring adducts isapossibility. Although thedatetheDr.Metzler hasbriefly presented
issuggestive thatsuchanadduct independent ofthenaturally-occurring adducts isinfactbeing formed.
Chairman
349. Thank youverymuch.
Mr.Christoforou (EC)
350. Mr.Chairman, Ithink wehavereviewed thepotential totoxicandcarcinogenic effects ofnow
allthesubstances inquestion. Thenextquestion isrelated totheresponse thedistinguished experts
gavetothequestion whether theJECFA report of1987 and1988 istaken intoaccount thistypeof
evidence which youhavebeenhearing thisafternoon. Asyoualready noticed, thisevidence hasstarted
appearing quite late,Iwould rather putitroughly, mid1980s anditisgrowing veryfastinthisarea.
Thescientists havereplied thatalltheseaspects ofgenotoxicity, synergistic effect, long-term exposure
tothese substances haveindeed beentaken intoaccount intheJECFA report. Butthere were very
strong differences inmyviews. Forexample Dr.Ritter would saythattheyhavenotaddressed
mutagenicity forallhormones, theyhave notaddressed definitive studies forgenotoxicity or
carcinogenicity ofcombinations although thisisthepreferred method foruse. Theother scientist,
Dr.Arnold forexample, would saythatgenotoxicity andcarcinogenicity havebeenexamined and
Dr.André would saythatsynergistic effects havenotbeentaken intoaccount. Iwould appreciate
ifallthescientists could summarize onceagain whether thissynergistic effect, thelong-term exposure
andthepotential effects orincreased effect fromtheuseofcombinations haveindeed beentaken into
account intheJECFA report. Andiftheyhavenotbeentaken intoeffect whatistheconsequences
ofthat? Dowehavetoreview thatreport nowinviewofthatevidence? Dr.Ritter hassaidthere
isnocompelling evidence thatweneedtoreview ittoday. Inhiswritten reply hesaidtheweight
ofevidence would notappear tosuggest thatthere isno,thattheyaregenotoxic andcarcinogenic.
Sothere aresome variations andslight nuances intheexpression. SoIwould appreciate ifwecan
come backonthisissue byhearing thefiveexperts onthis.WT/DS48/R/CAN
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Chairman
351. Didyougetthequestion andcould you,whowould liketostart? Dr.Ritter.
Dr.Ritter
352. ThankyouMr.Chairman.InthewrittencommentswhichIofferedwithregardtothexenobiotic
hormones, Ithinkthatitwillbeevident toallthatMGA forexample, hasnotbeensubjected toaJECFA
evaluation. AsIindicated earlier onintheday,myassessments weredrawn primarily, letmegofurther,
theyweredrawn entirely frominformation which waspublished intheopenliterature andobviously
dominated byJECFA reports andother ones. Itisclear thatMGA hasnotbeensubjected tosuch
anevaluation andconsequently, Ihavenoinformation other thanofaproprietary nature which Idid
notuse,fromthese evaluations toofferanypublic opinion onMGA. Insofarasthecarcinogenicity
testing ofthecombinations areconcerned itwillalsobeevident toanyreader oftheJECFA reports,
thattheassessmentsandconclusionsofferedthereinarebasedonthesinglecompoundthatwereevaluated
bytheCommittee anditwasinthatcontext thatIoffered those views. When Iconcluded thatthere
isnocompelling evidence tosuggest thatthese compounds should beimmediately re-evaluated, itwas
onthebasisagain ofmyunderstanding notonlyofthehistorical reviews which havebeencarried out
byJECFAandotherorganizations,butindeedhowmuchmorerecentreviews,includingthosepublished
asaresult oftheEuropean Conference onGrowth Promotion inlate1995, early 1996, andindeed
onthebasisofthestatements presented byourcolleagues heretoday, Dr.Liehr, Dr.Metzler andothers.
Ithink asDr.Liehr indicated, thework which hehascarried outrecently thework which others made
outrecently, thework which others havepresented recently, suggest thattherearecircumstances under
which adverse effects maybedemonstrated inassociation withthemultitude ofthese compounds.
ButIthinkthescientists inmyviewhavequitecorrectly noted thattheirrelevance tothedoses atwhich
thisdebate focuses isunknown, andI'msimply suggesting thatthatisnotinmyviewnecessarily a
reason toargue thatitshould therefore beimmediately redone. Inother words, letmeputitanother
way, ifMr.Chairman, anorganization likeJECFA orindeed anational regulatory authority, were
toimmediately conclude thatevery evaluation thatithadcarried outshould always besubject toan
immediate re-evaluation atanytimethatareport indicating thatthere arecircumstances under which
anadverse condition canbedemonstrated withaparticular compound, thenIwould respectfully submit
wewillalways bere-evaluating everything thatwehadeverdone. Because work goeson,notonly
onthese hormones butindeed onevery substance thatwecanthink of.Butasscientists, Ithink we
arecompelled tolookatthetotality oftheevidence asit'savailable. Ithink thattotality ofevidence,
certainly recognizing theinformation thathasbeen presented heretoday aswellasthehistorical
information, suggest tomethattheassessments thatwereprovided thencontinue toassure areasonable
degree ofsafety toconsumers ofthese commodities. AsIsaythisisnotonlymyopinion butinfact
itwastheconclusion ofaconference heldveryrecently andsponsored bytheEuropean Commission
onexactly thisissue. Thatthese compound when usedinaccordance withaccepted practice, Ishould
perhaps useaphrase thatwehaveallbeenusing, good veterinary practice, good practice intheuse
ofveterinary drugs, whichever acronym youwould liketouse. Ithink thishasbeentheconsensus
viewofthisConference ifyoulike.Iusethewordconsensus because clearly inanyscientific endeavour
ofthissortonecanquiteproperly andrealistically anticipate thattherewillbeadivergence ofopinion.
Thenature ofscientific interpretation isthatlegitimate bona fideknowledgeable scientists mayreach
different conclusions fromthesame setofdata. ButIthink theconsensus opinion ofthatConference
Mr.Chairman, wasthattheweight ofevidence usedthencontinues toprevail now, andthatthe
assessments andconclusions drawn thenarestillconsistent withtheavailable information now. Ithink
asDr.Arnold hasindicated, thisinnowayisintended tocastanydoubt orvalidity onthework which
others suchasDr.Liehr haveperformed. Andcertainly thissortofwork should continue, andIdon't
think anybody canassure youthatinsome timedown theroad, thatitwillnotrequire ordictate that
there beare-evaluation. Butaswesithereinthisroom today, Icontinue tobeofaviewthatthose
assessments served thecommunity wellthen, theinternational community, andtheycontinue todo
sonow. Andthattherehasnotbeencompelling evidence thathasbeenprovided tosuggest thatthose
assessments havebeeninserious error.WT/DS48/R/CAN
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Chairman
353. Thank youverymuch. Professor McLean.
Dr.McLean
354. Thank Mr.Chairman. I'llbebrief. I'dliketohighlight thefactthatinmysubmission Imade
nocomment about melengestrol acetate because there hasn'tbeenalarge amount ofdatapackage
available forevaluation andsoIrestricted mycomments totheother fivehormones. Theonlyother
comment Iwould make thatifanynational body orgroup believe thatthetimeforre-evaluation of
some ofthehormones previously evaluated byJECFA wasuponus,thenIwould invite themtomake
anapproach toJECFA ashasbeendoneonanumber ofoccasions withthenumber ofcompound of
varying chemical classes. Itisinteresting thatifthisinformation thathasconcerned some hasbeen
socompelling, toaskwhyanapproach toJECFA hasnotbeenmade.
Chairman
355. Thank youverymuch. Dr.Arnold.
Dr.Arnold
356. Thank youChairman. Concerning thetable Ihavepresented inmywritten contribution, I
justwanted tofacilitate thework ofthisPanel sothatyoudon'tneedtoreadallthese documents and
soIsummarize thekindofinformation, Iwassaying information pertaining totheeffects havebeen
considered bythestudy, it'sonpage9.Ihavenotstated thatIfeltthatallthisevidence wascomplete
atthattime, Iexplicitly mentioned thatsome datahadbeencompleted onlyatthe34thmeeting ofthe
Committee. Thiswasonlytofacilitate thediscussion. What concerns thesixsubstances, Imade no
statement onmelengestrol acetate because Ihaven 'tseenthedata. Theonlystatement Imade was
ontheavailability ofanalytical methods because thisissomething Iknow, butotherwise Ihavelimited
mystatements onthefiveendogenous hormones. Ididhowever saythatfrommypoint ofview, the
significant newevidence which hasbeenproduced since thatCommittee didnotinvalidate thebasic
conclusions andtherefore Istillamfeeling verycomfortable withtheconclusions although Iadmit
thatalotofnewevidence hasbeenproduced bythescientific community. Coming tothequestion
ofcombinations thesynergistic andantagonistic effects ofwhatever, Ihadsomedifficulties tounderstand
thisquestion because every timeifweadminister fixed combination toanimals orhumans, it'squite
clearandinallcountries participating inthisdispute therearemechanisms thatthesefixedcombinations
areevaluated. ButIdidn'tunderstand thesignificance ofthese questions when wearetalking about
theresidue levels because atthose concentrations, allthese substances occur simultaneously inhuman
beings ofallsexes allagesandit'squite obvious thatthese substances have bothsynergistic or
antagonisticeffectsinlivinganimalsincludinghumanbeings.Thisistheirnormalphysiologicalfunction
andtheycansynergize inonetissue inonecellwithrespect tooneeffect andtheycanantagonize each
other. Therefore Ihaddifficulties ifthese substances enter theinternal pools ofthehormones they
areimmediately confronted withallkinds ofhormones, soIdidn'tunderstand whatthequestion meant
attheresidue level. Atpharmacological levels ofcourse theyaretested inallstates iftheyare
administered asfixed combinations.
Chairman
357. Could youProfessor Epstein precise thequestion?
Dr.Epstein (EC)
358. Iamsorry thatmypoint thatIraised wassoobscure. Iwould havethought thatifyouadd
twocarcinogens toananimal ortoahuman, youstand theriskofinteractions ofonekindoranother.WT/DS48/R/CAN
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There aredatashowing thatarepositive interactive effects whether theybeadditive orsynergistic such
asthose between oestrogen andprogesterone. With oestrogen andprogesterone together, produce
afargreater increase inmammary cancers inrodents thandoeither separately. Sothatisclearwhat
onemeans bysynergism. I'munaware ofanyevidence ofantagonistic, anyexperimental evidence
ofantagonistic effects ofanyanabolics andwould behappy ifyoucould refermetotheappropriate
citations.
Dr.Arnold
359. Iagree withDr.Epstein thatthereareexamples ofsynergistic effects butIcould listanumber
ofsituations where these hormones counteract. I'mnotprepared atthemoment togiveyousuch
references butI'msureIcandoittomorrow.
Chairman
360. Dr.Lucier.
Dr.Lucier
361. Probably thebestexample istheonethatyoujustcited; oestrogen andprogesterone inwhich
oestrogen unopposed byprogesterone causes anincrease inuterine cancer. Ifprogesterone isgiven
atthesametimethenthateffect isblocked. Sowhere asoestrogen andprogesterone seemtosynergize
eachother interms ofbreast cancer risk,theyactually antagonize eachother foruterine cancer risk.
Soitjustpoints tothefactthat'sverydifficult tofullyappreciate thecomplexity oftrying toestimate
synergistic responses, additive responses orantagonistic responses. Even thesame twohormones in
different tissues willdoexactly theopposite, onesynergize, theother antagonize.
Chairman
362. Thank youverymuch. CanIgiveyouthefloor?
Dr.André
363. Wewillspeak about thesixhormones andnotofMGA, itisclearwearejustspeaking about
theother ones. Ithink thatconcerning thisquestion when JECFA hasconsidered these hormones,
theyhavebeenconsidered asdrugs, asclassical drugs andforthisreason, allthedataconcerning
toxicological assays hasbeenasked tocompanies andevaluated byverywellscientific expert groups.
ButIthink theyhavenotbeenevaluated asforthereviews forgrowth promoters, Imean withavery
largescaleuse.Ithink interference between thislargescaleuseofhormones andtheother drugs used
alsoinanimal breeding hasnever been studied, anditsclear thattheuseofhormones hasbeen
demonstrated tolonger some withdrawal period andelimination ratesofother drugs. Theprobability
tohaveinterference between twodrugs when theyareusedfortherapeutic useisverysmall because
youhavenoopportunity tohaveatthesame timetwodifferent illnesses andtwodrugs atthesame
time. Butwhen youareusing suchcompounds inlarge scale ashormones, thenyouhaveahigher
probability toseeonthesame animal atthesame timetheuseofthese hormones anduseofanother
drug. AndIthink inthisparticular caseofgrowth promoting substances, theassay hastobedone.
Andconcerning thenewscientific evidence wearespeaking about veryrecent datafromthismorning
altogether andIwould justmake tworemarks thatmany ofthese dataconcerning mode ofmechanism
ofaction carcinogenicity andotherarerecent datafrom'90tonowandmostofthemhavebeenpublished
during 1995and1996, thetwolastyears. Sothiscould alsoexplain insome ways thatmany ofthese
data,recent datahavenotbeentaken intobytheECConference in'95because thebibliography and
theinvestigation hasbeendoneforthisConference uptothebeginning of'95andnotmore recently.WT/DS48/R/CAN
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Chairman
364. CanIgiveyouthefloor?
Mr.Christoforou (EC)
365. Mr.Chairman, Dr.Liehr would liketomake acomment onthesynergistic effects andthen
Dr.Bridges would liketointervene ontheso-called 1995 ECScientific Conference whatwas.......
during thatConference. Then ifyouallow meIwillsummarize onceagain whatwassaidImaybe
making probably slightly legal butdirectly related question towhat istheJECFA standards inthis
caseandwhatisthelegalcontext inwhich wearelitigating inthiscase. Ithink thatwillbeimportant
forourscientists. Thank you.
Dr.Liehr (EC)
366. Mr.Chairman, concerning thesynergism ofhormones, Iagree withDr.Lucier whostated
thatthecombination ofoestrogen plusprogestin inhibits uterine tumour formation whereas itappears
toenhance mammary tumour formation. Itcertainly doessoinanimals andtheepidemiological evidence
inhumans isalsoquite strong. Inthiscontext, Ithink itisveryimportant forallofustorealise that
when several hormones arecombined andgiven asacombination thatthebalance ofhormones within
thebody, theregulation byvarious hormones appears tobealtered orinfluenced inways thatwehave
notsufficiently taken intoaccount. Ifforinstance progestin inhibits uterine tumour formation then
andenhances mammary tumour formation, thenitisobvious thatcirculating within allofusare
hormones inaquite well-defined balance andashumans proceed through life,through stages, the
endocrine regulation isquite wellbalanced. Once combinations ofhormones areadded thisbalance
isbeing destroyed andIthink anobvious example ofhowthis,effects, synergistic effects canarise,
isthefactthatthemetabolism ofoestrogen isclearly orhasclearly beenshown tobeinhibited by
progestins. Socombinations ofhormones theyeasily alter thebalance between these, between
endogenous hormone levels andforthemany synthetic progestins, Idon'tknow towhatextent this
isknown. Anumber ofsynthetic progestins havebeenexamined butcertainly notallofthem. Thank
youMr.Chairman.
Chairman
367. Thank youverymuch.
Mr.Christoforou (EC)
368. Mr.Chairman before giving thefloor toDr.Bridges, Iwould liketoclarify onepoint and
Dr.Stephany willintervene justafterwards. Dr.Ritter hassaid, JECFA evaluated onlysingle
compounds, single substances. From whatweknow inthemarket, theimplants, there isonlyone
implant thatisonesubstance onlymarketed. Alltheothers areimplant ofcompounds ofsimilar
substances andIthink Dr.Stephany would liketosayacouple ofwords about this. Soinfact,what
itisadministered totheanimals inthiscase, theyarenosingle substances except one. Themajority
ofalltherestoftheimplants areseveral compounds together. ThatIthink Dr.Stephany would like
tosayacouple ofwords onthis.
Chairman
369. Yes? Dr.Ritter please.WT/DS48/R/CAN
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Dr.Ritter
370. Idon'twanttopre-empt thecomments, butinaddressing theissue ofcombinations, I'mnot
sureifyouaredealing withtheissueofanimal safety, whopresumably would beatgreatest riskfrom
thecombination, ifthecombination wastoproduce synergistic effects? Because I'mleftwiththe
impression, perhaps these comments willbeaddressed, thatinterms ofhuman safety, theissueisthe
exposure tothelevels which arepresent asfoodresidues, which indeed arepresent incombination
withhundreds ofother substances, notonlythese twoalone. SoI'mnotsureifthecomments are
intended tobemore relevant totheissue ofsafety inthecow,ortotheissueofsafety tohumans who
consume commodities fromwhich theresidues mayindeed bepresent incombination butatverymuch
reduced levels andagain inpresent incombination notonlyforthetwosteroids inquestion, butindeed
present incombination withhundreds ofother residues ofbothnatural andexogenous origin.
Mr.Christoforou (EC)
371. Thank you,thank youverymuch indeed. Because there isoneaspect which isnotpractically
discussed inthisroom buthasbeenargued inthesubmissions oftheparties, especially insubmissions
oftheEuropean Community. Thiscaseconcerns boththefactsonhuman beings ofcourse, butalso
onanimals, andwedidnotelaborate because theeffects ontheanimals areevenmore obvious than
what theeffects areofthisresidue forhuman beings. ButDr.Stephany willalsogiven yousome
information onanimal health alsointhiscase, thatistheprostate ofanimals thatareaffected. Our
question isnotonlythepotential effects oftheanimals butalsothepotential effects ofthosecombinations
forhuman beings. Andthelinkthatwasmade, hasbeenexplained, issince theimplants which are
usedonthemarket, apart from onetheothers arecompounds ofseveral substances, thisislinked to
ourquestion, whatarethepossible synergistic effects ofthiscombination? Hasthisbeenstudied by
theJECFA Report? Thatwastheaimorthepoint thatweweretrying tomake. ButIgivethefloor
firsttoDr.Stephany thenwillcome backtoDr.Bridges. Thank you.
Dr.Stephany (EC)
372. Thank youMr.Chairman. FirstofallIhavetomake oneverysmall correction, oftheimplants
thatareonthemarket, there aretwohaving asingle active component butonlyonehaving oestradiol
andtheother oneiszeranol. Sothere aretwo,oneisoestradiol thebrand name isCompudose and
theother onecontains zeranol, xenobiotic andthename isRalgro. Allothers asfarasIamaware
arecombinations ofhaving atleastonexenobiotic hormonal active compound init.What surprises
mealittleisthatwealways talkabout, thattheimplants contain compounds thatareidentical tothe
natural ones. That'ssimply nottruebecause theimplants contain either thenatural onesinchemical
different formlikeanesterlikeoestradiol benzoate andorthetestosterone asatestosterone propionate.
Andatleasttestosterone propionate whatisxenobiotic circulates freely inthebodyasisknown from
clinical chemical studies, andI'mnotaware ofanyresidue studies oftestosterone propionate assuch
anditiscertainly nottruethatalltestosterone propionate oralloestradiol benzoate onlywillhydrolyse
andwillyield thenatural identical hormones. SoIthink that'sonething andcoming orresponding
totheremarks ofDr.Ritter, ifyouhavetwohormonal active components inyourimplants youwill
havetwoatleasttwohormonal active residues. Sotheconsumer willinhisfoodhave, inbetween
awealthofotherthings,Ifullyagree,theprobabilityofbeingservedwithtwohormonalactivehormones
orresidues atthesame time, atleasttwodifferent ones. Wellwhat'snext? Ohtheremark onanimal
health, it'sonlyasmall remark. Some recent research intheNetherlands with, picking upoldresearch,
weknow thatifyoutreatbull-calves withoestrogenic compounds thenatleastafeworgans willchange
liketheprostate andwithsome newtechnology based onhisto-chemical itsanewthing, wefound
thatatleastthiseffect ismuch more extended thanwehavefound previously. Whether thatwilleffect
thehealth oftheanimal assuch, Icanhardly sayespecially forcalves onlyhaving afulllifeofhalf
ayear. Butatleastit'sanother signal thatalotofthings change inthebody oftheanimal, besides
thatmoremeatisproduced. Andalsothat'sanitemthatistouched intheEuropean Conference, ranging
from animal health toanimal welfare, butthat'scompletely another thing. Ithink that'sitfortheWT/DS48/R/CAN
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moment, andonceagain Ithink themostimportant thing isthattheimplants donotcontain inmost
cases natural identical compounds.
Chairman
373. Thank youcould. I'msorry Imissed before Dr.Randell hewanted tointervene. MayIgive
youthefloor?
Dr.Randell (Codex)
374. Thank youMr.Chairman. Iwould notlikethePanel togoaway withtheideathatJECFA
didnotevaluate theresidues present inanimals fromthese mixed implants. Themonographs which
wereprepared byJECFA atthe32ndsession clearly indicate thattrials weredoneonmixed implants
aswellasonsingle substances implants andexactly thesortofmixtures thatwehavejustheard, that
is,oestradiol together withtestosterone; oestradiol together withprogesterone; oestradiol benzoate
together withtestosterone propionate andalsooestradiol withtrenbolone acetate under theoestradiol
evaluations. These wereknown toJECFA atthetimeandthepharmacokinetics ofthese substances
astheywere gradually metabolized andexcreted bytheanimals were studied bytheexperts atthat
time. Thank you.
Chairman
375. Sorry, Dr.Arnold.
Dr.Arnold
376. Thank youMr.Chairman. Dr.Stephany isabsolutely rightthattheesters areadministered.
However, thisisalsothecaseintheEuropean Union. Ifthesesubstances arelegally usedfortherapeutic
purposes because, andIthink heretherulesareentirely right, itisrecognized thattheesters arereadily
hydrolyzed toyield thesubstances. Therefore itdoesn 'tmake agreat difference ifwehavetalked
about oestradiol, testosterone andprogesterone because these esters areinfactreadily hydrolyzed.
Thereason whytheesters areusedisthatthefreesubstances aremore slowly released because we
discussed thisearlier today. Theplasma half-life issoshort. However, inorder togiveyouanidea
howineffective these substances stillare,when testosterone propionate wasusedinearlier times as
androgen substitution therapy, itwasnecessary toinject 25mg.every dayintra-muscularly, soalthough
heisfromanacademic viewpoint entirely right, Ithink wecancontinue discussing theeffects ofthe
freesubstances. Thank you.
Chairman
377. Thank youverymuch. Igivethefloor backtotheCommunity.
Dr.Bridges (EC)
378. Chairman, I'djustliketoclarify thenature oftheDecember 1995Conference because several
speakers havereferred toitasifitwasanup-to-date comprehensive riskassessment onsteroids. It
wasn'treally ofthatnature atall,ithadnearly 400participants, which isapretty difficult wayofgoing
about riskassessment. Itwascovering three areas, development ofnewgrowth promoters generally,
riskassessment across arange ofgrowth promoters andthenmonitoring andsurveillance. Sothere
wasn'tandthewaythepapers wereidentified wasthatwehadasmall organizing committee whochose
thespeakers. Nowintheirwisdom orotherwise, theychose nottohaveanybodywhowasinvolved
ingenotoxicity andsoasaconsequence, andIwasaplenary speaker forriskassessment soIremember
thebriefwell, asaconsequence thisissue ofgenotoxicity wasnotaddressed atallbytheconference
andtherefore theconclusions oftheConference didnottakeitintoaccount. Soitisn'tandwasneverWT/DS48/R/CAN
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intendedtobeacomprehensiveriskassessmentanditdidn'treallyconsideranyothermechanismbecause
ofthewaythespeakers wereselected other thanjusttolookatthehormonal mechanism andhowthat
mayberelated tocancer.
Chairman
379. CanIaskyou,thefactthatyoudidnotinvite speakers, wasthatanindication thatthiswas
notpartofthemainstream thinking atthetime, or?
Dr.Bridges (EC)
380. Chairman, Iwasn'tamember oftheorganizing committee buttheywere clearly verywise
because theychose measaplenary speaker soIcouldn 'targue withthem. Ithink really thethinking
wasthattheywanted tofollow uptotheso-called Lamming Report, andtheLamming Report had
concentrated verymuch onhormones acting ashormones orhormonal mechanism. SoIthink the
natural assumption wasthattheywould getanupdate onthose sortofissues rather thanlookatbroader
issues andI'vetaken theopportunity totalktomembers oftheorganizing committee recently toconfirm
thatthatwastheirview.
Chairman
381. Butcould itbesaidthatifthiswould beorganized today theywould probably takeadifferent
approach? Isthat,Imean these issues we'rediscussing havetheymoved intothedebate?
Dr.Bridges (EC)
382. I'msureChairman thatifwewereorganizing thesame conference today, genotoxicity issues
would loom verylarge inthediscussion andI'msureIwould havehadtorefertoitparticularly in
mypaper.
Chairman
383. Thank youverymuch. Dr.Arnold.
Dr.Arnold
384. Thank youMr.Chairman. Itotally agree withyouthatthisConference hasnotproduced the
slightest element ofriskassessment, Itotally agree withyou.ButIhaverecognized thatsome important
information hasbeendisseminated including yourownveryimportant keylecture, butIwanted to
underline thisConference hasnotproduced theslightest element ofriskassessment.
Chairman
385. Thank youverymuch. Dr.Ritter please.
Dr.Ritter
386. Thank youMr.Chairman. Ithink itmaybeuseful, anumber ofushavereferred tothereport,
Ihavethereport withmewhich Ibrought attheriskofgreat personal injury totransport it...[tape
ends]
Mr.Christoforou (EC)
387. Itisaddressed, particularly forDr.Ritter, Dr.McLean, Dr.Arnold andofcourse, Dr.Randell.WT/DS48/R/CAN
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Chairman
388. Thank youverymuch. Could IstartwithyouDr.Randell because theprocedural questions
areaddressed toJECFA.
Dr.Randell (Codex)
389. Thank you,Mr.Chairman.
390. FirstI'dliketosaythattheJECFA Secretariat, ofwhich Ihadthehonour tobeapartfor
aperiod ofmycareer, would feelverydisturbed iftheywere aware thatdatawere available tothe
scientific community thatwerenotavailable toJECFA, orwere notbeing proposed tobeavailable
toJECFA, inamanner thatwould render JECFA 'sadvice toFAOandWHO member countries, either
obsolete orinappropriate.
391. Therefore, mycomment earlier, wasreally tomaintain, what Ibelieve tobethestanding
excellence ofJECFA 'sevaluations inallofthefields thatJECFA deals with, inorder that,wecould
perhaps encourage those scientists thathavethese datatoassemble them andbring them toJECFA
forreview. Itwasmeant asapositive, notanegative, statement.
392. Afewminor corrections tothehistory which we'vejustheard. Thevotewhich tookplace,
inwhich thehormones werefailed tobeadopted bytheCodex Commission, wasin1991, not1992.
393. Thefourprinciples concerning theroleofscience inCodex decision-making, andtheextent
towhich other factors aretaken intoaccount, wasnever discussed, asfarasIamaware, byJECFA.
Itwasnotprocessed through theJECFA system. Itisentirely aCodex matter and,therefore, entirely
operated bythemember governments ofCodex andnotbytheexperts inJECFA.
394. LetmeputtheJECFA material intoperspective. JECFA provides advice toFAO andWHO
andthrough them tothemembers ofthose twoorganizations andalsototheCodex Alimentarius
Commission.
395. TheCodex Alimentarius Commission has,asamatter ofprocedure, taken theJECFA
recommendations inavariety ofareas andplugged them intotheeight-step elaboration system and
theresult ofthis,inmostcases, isaconsensus adoption ofthesepoints ofviewwhich arethenavailable
forcountries toapply, iftheyfeelthattheywishto.They arenotobliged tounder theCodex rules.
396. There havebeenanynumber ofemergency re-evaluations inJECFA which havebeeninitiated
inCodex andwhich havefound themselves reflected inCodex opinion.
397. Astothedirect question ifthere isonethathasoccurred inthenine-month period since the
entry intoforce oftheUruguay Round Agreements, I'dhavetocheck thatinbutIcan'tthink ofone.
Themostrecent onewhich hassimilar import would bethedecision ofJECFA towithdraw previous
evaluation inregard topotassium bromate, asaflour-treatment agent, andthesubsequent withdrawal
byCodex ofallapproved usesofpotassium bromate inflour, primarily because potassium bromate
residues remain intheflouratthetimeofingestion bythehuman consumer, andpotassium bromate
isacarcinogen.
398. Themaximum residue limits arenotexclusively concerned withtrade. They areconcerned
withthecontrol ofgood agricultural orgood veterinary practice andtheyareapplied intrade. To
bequitepractical about it,it'sdefinitely beneficial totradeifcountries havethesame numerical values
formaximum residue limits, oratleastifyouareexporting aproduct, thelevel atwhich youare
exporting islower thanthelimitapplied byyourimporter.WT/DS48/R/CAN
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399. However, themaximum residue levelshould reflect thegoodagricultural, orgoodveterinary
practice, onyourterritory andnotbelinked exclusively totrade considerations.
400. Iwould takeumbrage atthepoint thattheMRL isatrade-derived figure. Itis,infact,afigure
derived from good veterinary orgood agricultural practice.
Chairman
401. CanIaskyoutogointothequestion which wasputforward?
Dr.Ritter
402. Veryquickly, Ithink theprinciple thatwasbeing elaborated, thephilosophy ismore popularly
referred toastheprecautionary principle.
403. Astowhatisthemostappropriate action inthefaceofthekindofinformation, forexample,
thathasbeenpresented today, Itakethatreally tobethework ofthePanel, andsoIwillmake no
attempt toanswer thatquestion.
404. Ithink itgoeswellbeyond thejurisdiction thatI'vebeenprovided heretocomment.
405. Iwill,veryquickly, comment on,ifyoulike,theageoftheassessment andI'vealready made
comments onthisanumber oftimes, butitperhaps bears repeating.
406. Ithink itisincorrect andIwould respectfully submit thatitismisleading tosuggest that
1988/1989 isthelasttimethatthisissueonthesafety ofthehormones, inquestion, hasbeenexamined.
407. I'vealready mentioned thatcertainly inmyview, thisissue, without going intoalengthy debate
astowhether ornotthestrict definition ofriskassessment wasmade bytheEuropean Conference,
Ithink itgoeswithout question thattheissue ofthesafety ofthehormones, inthegeneral sense, was
most certainly re-evaluated inDecember 1995, which isalittlemore thanoneyearago.
408. Indeed, anumber ofpeople whoareheretoday were active participants atthatconference.
409. ImustsaythatIdisagree withtheviewthat1989 isthelasttimethatthisissue wasformally
evaluated onaninternational level. Ithink that'sincorrect andIthink it'smisleading.
410. More specifically, ontheissue ofriskassessment, whatever thatmeans. Wecould spend the
restoftheevening debating whether ornotriskassessment have, orhavenot,formally beendiscussed
bytheConference.
411. Iwould refer thePanel toaspecific section entitled, Risk Assessment, onpage 3ofthe
Conference Report, anditfallsunder thegeneral section oftheReport entitled Report andConclusions
oftheSteering Committee, specific section entitled, RiskAssessment.
412. Although theConference wasconcerned withmany technical matters, itisinevitable thatgeneral
interest should havecentred ontheriskassessment ofdifferent classes ofbothpromoting substances,
thesubject ofdiscussions ofWorking Group 2.
413. Then Iwould refer, Mr.Chairman, thePanel toanumber ofspecific papers which Iwould
respectfully submit, dealtwithverymuch withtheissueofriskassessment. IrefertoWorkshop No.2
onpages 245-401 andIwould referspecifically toanumber ofpapers, including theonepresented
byProfessor Bridges, butalsoincluding papers presented byDr.Miller from theUnited States,
Dr.Hoffmann from Germany, andsoonandsoforth.WT/DS48/R/CAN
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414. IfIrefer, justbywayofexample, nottogiveparticular preference toanyoneofthese papers,
tothepaper presented byDr.Miller fromtheUSFDA atthatConference, sheconcluded, atthattime,
"hormonalgrowthpromotingagentsincludeavarietyofcompoundwhichverymarkedlyinpharmacology
andbiochemistry" soonandsoforth.
415. "When these animal drugproducts areusedaccording tolabel directions, theedible tissues
from treated animals, aresafeforallconsumers."
416. Iwould respectfully submit, Mr.Chairman, thatthatisverymuch anassessment ofrisk,
regardless ofwhether ornotwecancome toaformal definition ofwhatconstitutes ariskassessment.
It'scertainly myviewthatthisismostdefinitely theelement ofriskassessment. Itstrikes theheart
ofwhatariskassessment is,because afteralltheproduct ofariskassessment, isthestatement ofsafety
tothetarget population. That'swhywecarry outriskassessments. It'snotmerely amathematical
exercise.
417. Iwould suggest tothePanel thatthere areanumber ofpapers herethatdealverymuch with
theissueofrisktohuman populations, resulting fromtheuseofthesecompounds, andthattheconsensus
ofthisWorkshop wasthattheuseofthese compounds, asrecently reviewed asDecember of1995,
doesnotconstitute anyrisk.
Dr.André
418. MayIaddsome comments forthePanel? Itcanalsoseeinthesame paper, page378,
conference.
419. Iwillreadwhatitsays:
"New quantitative riskassessment models areneeded forthesafety evaluation ofchemicals
withtoxic actions, likegeneral carcinogen."
420. It'sinthesame paper soit'snotpossible toextract something when youdon'textract allthe
information.
Dr.Ritter
421. Ididn'tintend tomislead. Imean obviously I'mnotgoing toreadintotherecord theentire
Conference Report itisavailable.
422. There isnoquestion thatanumber ofdeficiencies, interms ofourstateofknowledge, as
identified throughout thereport, butthoseefficiencies, thosedeficiencies wereweighed intheconclusion
which thePanel hasreached. They weren 'tweighed byme.Buttheconclusions oftheWorking Group
wasthatthepresent stateofknowledge issufficient todemonstrate thesafety, intheirview, ofthe
useofthese chemicals incontemporary times.
423. Ithink itwould besillyforanyscientist topresume thatthedaywillevercome, onthisissue
oronanyother, where wecould sayweknow enough andthatthereisnoneedtodoanyfurther work.
Ihavenever beenassociated withascientific issue where Ihaveeverheard ascientist say,there is
noneedtodoanyfurther work onthistopic, weknow allthatweneedtoknow.
424. Iagree thatthere isfurther work thatisindicated. Iagree thatstatements made byscientists,
suchasDr.Liehr willcontinue tocontribute toourunderstanding, butIalsoagree thatthetotality
ofevidence re-evaluated, asrecently asDecember 1995, suggests thatthewayinwhich thesesubstances
areusedandtheresidues which theyproduce, donotconstitute arisktohuman health.WT/DS48/R/CAN
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425. Idon'tfindthose statements tobecontradictory atall.
Chairman
426. Dr.Lucier.
Dr.Lucier
427. MyquestionmayshowacertainamountofnaivetybutdidJECFAdocumentorthe1995meeting
address theissue ofcarcinogen riskassessment, inanykindofway?
428. Itseemed tomeliketheriskwasbased onthehormonal activity oftheagents, inprimates.
Chairman
429. Wediscussed thatbriefly before. Would youliketogiveyourviews onthis.
Dr.Ritter
430. Ithink onlytosaythatunless weweretospend agreat dealoftimestrictly defining whatwe
mean bythephrase "risk assessment" wecould continue togoaround thiscircle, Ithink, allnight.
Thepoint thatIwastrying tomake that,intheopinion ofthescientists thatwere gathered atthe
Conference, itwastheircollective wisdom, forwhatever reasons theyconsidered. Ithink, asProfessor
Bridges hasalready quite correctly indicated thatitdidnotinclude extensive examination ofsome of
theevidence which waspresented today. Butforallthetotality ofreasons thattheyconsidered, at
thattime, theycame toconclusions which havealready beenmade clear. Onemayraisethequestion
iftheywereredoing ittomorrow, would theycome tothesameconclusion? Ithink thisisspeculation.
Onecould raisethequestion, iftheyweredoing itagain ayearfromnow,would theycome toadifferent
conclusion? Idon'tknow.
Dr.Lucier
431. Were theacceptable levels, ortheacceptable dailyintakes, weretheyderived, primarily, from
thetestsofhormonal activity innon-human primates? Isthatcorrect?
Dr.Ritter
432. No,Idon'tthink that'scorrect. Ithink there were extensive carcinogenicity datathatwere
available totheJECFA Committee. These datahavebeendescribed, theassessments provided, at
leastinthecaseoftwoofthexenobiotic hormones. Tothebestofmyrecollection, monographs on
thethreenatural hormones arenotavailable, buttheyareavailable forthetwosynthetics, andcertainly
theywerebased onchronic toxicity carcinogenicity studies thathadbeenconducted inaveryclassical,
NTPkindofmethodology.
433. No,thenaturals wereevaluated, whatIindicated, tothebestofmyknowledge, monographs
arenotavailable onthenaturals. Butdatawasevaluated bytheCommittee, onwhich theydrewtheir
conclusions, Ihavenotbeenprivy tothatdata. Butthenagain, Ihavetobecandid, Ihavenotre-
evaluated thecarcinogenicity dataforanyofthese compounds, inorder toprepare thissession. This
would havebeenneither practical orarguably evennecessary. Iwould never pretend tosuggest that
Ihavegreater wisdom inthisareathanthecollective wisdom oftheJECFA Panel.
Chairman
434. Dr.Randell, please.WT/DS48/R/CAN
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Dr.Randell (Codex)
435. Mr.Chairman, justperhaps toclarify thatpoint.
436. Inthecaseofzeranol, forexample, theJECFA Committee didevaluate carcinogenicity studies,
inratsandinmice, andsoforth, buttheconclusion thatJECFA came tointhissubstance andinthe
other substances, thatthecarcinogenicity waslinked withthehormonal effect, andtherefore the
establishment ofthe"nohormonal effect" levelwasthepoint atwhich theevaluation hinged, ithinged
around thatpoint.
437. Thisiswhythenewdata, which we'rehearing about today, isofinterest because itwould
supplement thatevaluation andhelpusconsiderably. However, theinformation which wasavailable
toJECFA definitely didinclude carcinogenicity studies forallofthesubstances concerned.
Chairman
438. I'mlooking atmywatch. It'sabout 7.30. Could youcome toaclose fortoday?
Mr.Christoforou (EC)
439. Mr.Chairman, Iwillcome toaclose onthisparticular point, ifyouallow me.
440. Iwillreadfromwhattheresponse ofDr.Ritter wastoQuestion No.5,because thatiswhat
wearediscussing now.
441. Iquote page12ofhisreply toQuestion 5,attheendofthefirstbigparagraph:
442. Forprogesterone:
"The report wassilent ontheresults ofmutagenicity studies which were available tothe
Committee forreview."
Fortestosterone:
"Results frommutagenicity studies, although available totheCommittee, werenotdescribed
inthereport."
Forthesynergy:
"The issue ofpotential synergy hasbeenaddressed, atleastinpart,through thecontext of
biochemical studies, directed attheeffect ofexcretion ofhormone combinations when compared
tosingle hormones alone."
Thisisonpage14.
"Itis,however, clear, thatdefinitive studies relating togenotoxicity orcarcinogenicity of
hormone combinations havenotbeencarried outeventhough thisisfrequently thepreferred method
ofuse."
443. I'mslightly puzzled bythepositive terms inwhich Dr.Ritter isnowphrasing hisreplies for
thereview ofthe,intheJECFA report. Allissues wehave beendiscussing herenowabout the
genotoxicity, notonlyduetothehormonal effects, ashasbeenrightly pointed byDr.Lucier butall
theother possible sources ofriskswehaveidentified.WT/DS48/R/CAN
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444. AtleastthewayIunderstand hisreplies isthatthese studies havenotbeencarried out.They
might havebeenavailable buttheyhavenotbeenreported inthereport. Wedon'tknow iftheywere
realstudies.
445. HewasnotpartoftheJECFA committee, inthatparticular case. SoIdon'tknow where he
hasgotthisinformation. Whereas Dr.McLean waspartofthisreport andalsohemight haveaninterest
toexplain touswhether thishasbeendone. From thereports wehaveinfront ofus,Dr.Arnold
hasprovided atable, where there aresome black holes where things which havenotbeenexamined.
Iseethere is,atleastsome, contradiction between what ourscientists aresaying onthisparticular
issue. Ifonereads theentire report ofJECFA, itisclear thatonlythehormonal effects ofthose
substances havebeenstudied forthepotential carcinogenic effect. Sowhatistheexact scientific basis
onwhich Dr.Ritter ismaking these comments?
446. Onemore comment.
447. Ithink Dr.André, because hewaspartoftheOrganizing Committee ofthe1995Conference,
hehas,inmyview, direct inside information onhowthisconference wasorganized. TheCommunity
onlyfunded theConference andleftthescientists entirely toaddress some issues.
448. Inthereport ofDr.Ritter, itisfrequently referred toastheECConference. ItisnottheEC
Conference. Itisaconference funded, butnomore thanthat. Itwasentirely lefttotheSteering
Committee whotoinvite andwhattodiscuss inthisconference.
Chairman
449. Iwould propose thatwehaveafinalround onthisquestion andthenwewillclosethemeeting
fortoday, andIwould givetheopportunity torespond tothescientific experts.
450. Maybe Dr.Ritter would speak attheend.
451. I'llstartwithDr.McLean.
Dr.McLean
452. Ithoroughly concur withthecomments ofDr.Randell. Weweretrying toputapositive view
ontheavailability ofJECFA, ifpeople wanted totakethatopportunity, rather thanforcing people
todoit.
453. Inrelation tothemutagenicity dataforthenaturally-occurring substances, themutagenicity
datathatwasreviewed isreferenced inthereport, ineachcase, andsotherefore, notsomuch that
iswassilent butitreferred tomutagenicity datathatwasintheopen literature. So,inthecaseof
progesterone, testosterone andoestradiol 17beta, there wereanumber ofpublished documents that
theCommittee didlookat,andtheyarereferenced inthereport.
Chairman
454. Dr.Arnold.
Dr.Arnold
455. Mr.Chairman, Ihavetwopoints.WT/DS48/R/CAN
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456. ThefirstpointisIhavedifficulty understanding howitcould happen, butthelegally competent
authorities oftheEEC, ontheadvice ofthecompetent advisory scientific body, haveestablished no
MRL foroestradiol andthishappened twoyears ago.
457. Thepublic summary report states, inter alia,"The conclusion oftheFAO/WHO Expert
Committee onFood Additives, JECFA, thatnoADIandMRL foroestradiol needtobeestablished,
asadopted." Andthenalltheother things Imentioned thismorning, thisiswhat Ihavedifficulty
inunderstanding, thishappened in1994. AndthisRegulation hasbeenimplemented, ithaspassed
alltheECinstitutions andtheresult hasbeenpublished intheOfficial Journal. Irefertothisinmy
answers tothequestion ofthePanel.
458. Mysecond point isIwasrapporteur oftheCodex forfiveconsecutive years. Thatmeans
Ihadjointly, withthesecretaries ofthetwoagencies oftheUnited Nations andwiththeUSSecretariat
oftheCommittee, toprepare thereport. Iwasinareally difficult situation because it'struethatthe
ECobjected tomove these MRLs tothenextstepintheprocedure, butwithout raising anyhealth
issues. So,Iwasreally introuble andyoucanfindtheresult inthereport. Ifinally gotawritten
statement andthearguments youwillfindthere are,interalia,theECisopposing because theyhave
specific legislation prohibiting theuseandtheECconsumer doesn 'twishtoreceive meatfromanimals
treated.
459. These werethearguments, soI'malittledisappointed thatthesequestions havenotbeenraised
earlier, firstofall,inearlier years during theCodex discussions. Itcould havehappened, forexample,
toreferthewhole matter backtoJECFA withnewhealth arguments forre-evaluation, atthattime,
butthisproposal wasnotmade.
460. Andthatsecondly, twoyears agoithappened thatwecame tothesame conclusions bythe
competent authorities oftheECregarding oestradiol. Progesterone hasalsobeenfinished butnotyet
published intheOfficial Journal, andtestosterone isstillunder evaluation.
Chairman
461. Ithink wewillreserve thisfortomorrow.
462. I'dliketoconclude andifanybody ofyouwould liketospeak?
Dr.André
463. Justtosayalittlemore about thisConference because Ihavebeenasked todoso.
464. It'sclearthattheEChasjustasked fourexperts toorganize thisConference: SirJohnMaddocks
istheHead Director oftheNature Review, ascientific paper, anIrishcolleague, Bergen colleagues
andmyself.
465. Icanwitness thatwewerevery, veryfreeofourtoourchoices, interms ofselecting scientific
people. Andweorganized thiswithafirstgroup oftwopeople forthethree Work Shops, andthey
proposed thatweinvite scientific people andweagreed, onthebasisofthepublication andthefamous
ofthese people.
466. But,Ithink, andIpersonally regret nowthatwedidn'ttakeenough carewiththescientific
publication. Idiscovered thismorning alotofpublications onthistopicandsomeofthemwereavailable
andthescientific werealsoavailable, andmaybe wehavenotdoneourbest. Wehavedoneourbest
butmaybe itwasnotgood enough, andthatwillexplain alsothemissing ofsome information inthis
Conference.WT/DS48/R/CAN
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467. Onthelastpoint,Iwouldliketosaythattheconclusionsareareflectionofacommondiscussion,
anditisnotacomplete reflection ofthemajority ofpeople. Itisnotatotalopinion ofthemembers
oftheCommittee anditcannot betaken intoaccount assomething coming from anofficial body.
Ourobjective wasjusttoputsome light, some knowledge, onthese hormones inorder toinform
politicians preparing newregulations andnomore. Itisnotthesame thing astoestablish anofficial
MRL. Theresponsibility wasnotexactly thesame order.
Chairman
468. Dr.Lucier.
Dr.Lucier
469. I'mjustsurprised inreading through thisreport that,given thefactthatoestradiol isaknown
human carcinogen, thatanADIwasconsidered unnecessary forit.There isatolerance butnotan
ADI, ifI'mreading thereport correctly.
Chairman
470. What page?
Dr.Lucier
471. 19.
Chairman
472. TheJECFA Report. Thiswasthe1988 JECFA Report. Isthatcorrect?
Dr.Lucier
473. Inthemiddle ofpage19itsaidtheCommittee considered anADIunnecessary forahormone
thatisproduced endogenously inhuman beings andshows great variation andlevelaccording toage
andsex.
Dr.McLean
474. Thedifficulty thatJECFA hadofsetting anyADIwastheproblem oftheincrease thatone
sawupontreatment, against abackground ofverylargelevels thatoccurred naturally. Andsotherefore
itmeant thatthesetting oftheADIreally wasn'tpossible, because thetreatment altered thelevels by
suchasmall amount when compared withtheendogenous levels incattle tomake anyADImeaningless,
andthatwasthedifficulty wehad.
475. Iwould suggest, today, thatisnotpossible toregulate theuseofthethree naturally-occurring
hormones bythesetting ofanADIbecause youcan'ttellthedifference between treated animals and
untreated animals, byamethod thatissuitable forregulatory purposes.
476. It'sapractical consideration, arealandpractical consideration. Idon'tquarrel withwhatyou
say,butinpractise there'snowayofregulating it.WT/DS48/R/CAN
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Dr.Lucier
477. Butifoneknew, which wedoknow, whataregiven bodyburden inthecattle would beproduced
bytheuseofgrowth promoters, wecancertainly estimate various eating habits ofpeople, whatthey
would takeintheirbody from those agents thatwere exogenously administered.
478. Onecould come upwithreasonable estimates onthatandestablish anADI. Inmymind, that
could bedone. From mycomments thismorning, Idon'targue withyourpoint thatit'saverysmall
number ofmolecules, onein28,000 Icame upwithinmycalculations, nottaking intoaccount the
factthatitispoorly absorbed andthatwould make itonein280,000.
479. Butnevertheless, some sortofanassessment should havebeenmade, inmymind, ofwhat
thatriskwas,aslowasitis.I'mnotsaying thattheriskishighbutIbelieve theriskisextraordinarily
loworzero. That'snotmypoint. Iamjustsurprised thatthatexercise wasnotdone.
Chairman
480. Ifmore points onthisaretobediscussed, Iwould liketodiscuss them tomorrow because I
think wearealittletired.
481. Would youliketomake statements tonight?
482. Iapologise forthelength ofthemeeting butithasbeen, inmyview, veryinformative and
Iwould liketothank theexperts andalsothedelegations fortheirsupport.
483. Asagreed, wewillmeettomorrow at2o'clock, hopefully sharp, andwewillopendiscussions
withthestatements andquestions bytheCanadian Delegation.
484. Thank youverymuch andgood night.
485. Themeeting isclosed.
Second day-18February 1997
Chairman
486. Asannounced yesterday, weshallproceed inthefollowing manner. WewillgofirsttoCanada
fortheircomments andquestions totheexperts. Wewillthenturnagain totheEuropean Communities
andIwould urgetheCommunity tolimittheirinterventions totheutmost necessary inorder tosave
time. Wewillseehowmuch timecanbeallocated when theCanadians havemade theirstatements
andquestions andthenthere willbefinalquestions from thePanel totheexperts andthenthefinal
statements bytheexperts intheend. Ihavetobeabletoconclude thismeeting byaround 6o'clock.
Iamnotabletosaywhether wewillbeabletodoso.Itdepends onyouandIaminyourhands to
alarge extent.
Mr.Christoforou (EC)
487. Wewould really doourbesttorespect whatyouhaveindicated, butourdelegation hasaserious
problem inthesense thattheplanes oftwoofourscientists areleaving at6o'clock andweconsider
theirtestimony andtheirpresentation veryimportant. Itisjustarequest andwehopewehavethe
understanding ofthePanel inthisroom. Ifitispossible by4o'clock, Canada doesnotfinish, Ido
notknow howmany questions theyhave, ifwecanstopforawhile theycanmake theirpresentationsWT/DS48/R/CAN
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andifthere areanyquestions oranswers andthentheycould probably beabletotaketheirtaxisand
gettotheairport intime. Thatistherequest.
Chairman
488. Thank youverymuch. Ithink wewillseewhere wearewithCanada at4o'clock.
Mr.Brinza (US)
489. Mr.Chairman, aprocedural question. Lastnight wehadleftthatthePanel wasgoing to
deliberate onourquestion about thefollow-up submission. Thatwasrequested bytheEuropeans and
Iwondered ifthePanel hadcome toaconclusion withrespect tothematter wehadraised lastnight.
Itisimportant, inpart,because asweunderstand, theprocedure thatwasjustdescribed, there would
benomore opportunity forcomments byeither Canada ortheUnited States aftertheCanadians have
finished theirquestions today (andobviously wefinished ourquestions yesterday), andthere area
number ofpoints thathavebeenmade thatIthink itwould beappropriate togiveusanopportunity
torespond to.
Chairman
490. Thank youverymuch. Iintended totakethisupattheendofthemeeting butsince youraise
itIcangivetheanswer ofthePanel. Wehavelooked intothequestion andbased uponthetextwhich
wascommunicated on3February bytheSecretariat totheParties, which Iwillreadinasecond, we
reviewed thedecision Imade yesterday andwewillnotaccept anyex-post submissions fromtheParties.
TheUnited States hassubmitted some materials, youhavesubmitted some materials yesterday which
wetookonthefile,butwewillnottakeonanymore written materials afterthisday. Thetextreads
"Please findattached theresponses offourofthefivescientific experts responses toPanel questions.
Professor Arnold requested afewmore daystosubmit these responses. [They came lateron.] The
Parties areinformed thattheircomments tothesequestions atthe17-18 February meeting withscientific
experts should bemade available, asiscustomary withtheParties 'oralstatements atpanel meetings,
inthewritten formandifpossible ondiskette totheSecretariat". Sothismeans thatweexpected these
comments bytoday andIthink wewillconclude theproceedings based onthisletter. Soifyouhave
additional materials, please handthem inbytheendofthismeeting.
Mr.Christoforou (EC)
491. Mr.Chairman, thepractice though isthatweareallowed tosubmit adocument atleastthe
nextdayaftertheoralpresentation. Thishasalways beenthecase. Weareadjusting thetextwhile
wearespeaking andIhavebeendoing thatforsomany years anditisalways thenextdayweare
allowed tosubmit inwriting theoralpresentation. Itisveryrestricted thistime-limit oftoday. Iwould
appreciate itiftomorrow there isalsoachance forustosubmit adocument. Thank you.
Chairman
492. Ithink theproblem isthatthenweneedtohaveanother goonrebuttals. AndIthink westick
tothishereforthemoment because thishasbeenahearing ofexperts byapanel andwedorecord
ontapeandwilltranscribe everything which isbeing saidatthismeeting soIdonotthink thatwe
would needanother written statement onthesideofyourpart.
Mr.Christoforou (EC)
493. Mr.Chairman,ifyouapplythisrulethentheentiretextwhichisinthetextthattheUnitedStates
hascirculated hasnotbeenreadoutorally. Then Iwould haveunfortunately torequest youtoexcludeWT/DS48/R/CAN
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allthose partsofthedocuments which havenotbeenreadout.Ireally regret thatinthispartofthe
document there aresomany things which havenotbeensaidyesterday.
Chairman
494. Ithink itwasnotrequired thatthisbereadoutbecause itsaysthatthecomments onthese
questions should bemade available totheSecretariat. Itisnotexactly thesame proceeding inmy
viewasintheordinary firstandsecond substantive meetings here. Idohopethatyouareabletoprovide
some ofthematerials asitwasdoneyesterday, today -thestatements bytheexperts andsoon.
Mr.Thompson (Canada)
495. Thank youMr.Chairman. IfIamgoing togetstarted before my4o'clock deadline thenI
hadbestgetquicker withthefinger onthebutton.
496. IthadbeenCanada 'soriginal intention tocomment quite briefly ontheexperts 'answers to
thePanel'squestions. Primarily bynoting inpoint form some seven areas where theexperts were
ingeneral consensus andthentoputwhatwehoped were afewfocused questions. Westillintend
todothat,however some oftheevents ofyesterday require some broader comments onCanada 's
understanding ofthepurpose ofthismeeting andtherulings thatyoumade onhowweweretoproceed.
497. Wecame hereprepared tocomment onandexplore thePanel ofExperts 'answers toyour
questions andabide byyourruling thatnonewevidence would beintroduced after8February. Ibelieve,
Mr.Chairman, thatyouwillrecall thepurpose ofthatruling wasintended toprovide allparticipants
withanequal opportunity toreview relevant material inadvance sothatinformed commentary could
bemade.
498. Yesterday weallhadtheprivilege tohearsome oftheworld 'sleading experts comment and
debate theproperties andcharacteristics ofthesubstances inissue. Some highly technical andcomplex
issues werediscussed withclarity andprecision. Unfortunately andunfairly, inCanada 'ssubmission,
weweresometimes deflected fromthatveryhighlevelofdebate bytheintroduction ofnewmaterial,
some ofwhich wasapparently presented outofcontext andinaselective way. ThePanel'sexperts
were asked tomake extemporaneous replies onmatters theyhadnothadanopportunity toconsider
inadvance. Thissometimes ledtoprolonged discussion clarifying facts onmatters ofmarginal
importance totheissues thisPanel must decide.
499. Anexample, nobetter orworse thanmany Icould choose, isDr.Epstein 'stableonoestradiol
residues ineight-year olds, which ultimately ledtothesomewhat surprising assertion thattwo
quarter-pounders or110gram whoppers were theequivalent of500grams ofmeat. IfIcould be
permitted apun,thatwasarealwhopper! With respect, itisimportant torefocus theissues these
experts areheretohelpelucidate.
500. Thecomplaint before thisPanel concerns ameasure oftheECwhich banstheimportation
ofbeeforanyofthesixhormones, alone orincombination, thathavebeenusedforgrowth promotion
purposes inthefaceofproperly established international standards ofsafeuse.
501. OnegoaloftheSPSAgreement istofurther theuseofharmonized sanitary measures between
Members soastoprotect health butnotunnecessarily interfere withtrade. TheAgreement permits
aMember todepart from these standards forcertain prescribed circumstances. Therelevant onefor
theissueconcerning thePanel'sexperts, andtheonlyoneinmysubmission, isascientific justification.
Dr.Randell hasspoken eloquently ofthehighstandards ofJECFA andCodex andthesubject matter
thatwastaken intoaccount inestablishing thestandards ofboththenatural andsynthetic hormones
andtheveryconservative assumptions adopted toensure safety through theuseofADIs andMRLsWT/DS48/R/CAN
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where required. Itisclearthatthese organizations aretobecommended fortheirwork andnurtured
rather thancriticized.
502. Wehavelearned thatstudies havebeenconducted formore than12years totryandprove
ahypothesis thatoestrogen isgenotoxic. Many ofthese studies were known toandconsidered by
JECFA. Dr.Liehr, inoneofhisstudies, hasinjected comparatively massive doses ofoestrogen in
amaleSyrian hamster inanexperiment designed toproduce tumours. Thequantities areabout twice
thedosegiven tocattle. Dr.Lucier, asIunderstood him,agreed thatinlightofthisevidence there
wasarisk,butheputsthatriskatalevelsomewhere between zero, aconcept which cannot beachieved
inabsolute terms, andafactor sosmall thatitcannot bemeasured.
503. Thequestion forthisPanel isthisinmysubmission: isthatariskthatjustifies departing from
aninternational standard inlightofitsimpact ontrade andtheobjects oftheAgreement. Oneway
oftesting that,Mr.Chairman, isbycomparing other ECsanitary measures where there aresimilar
orgreater risks. Canada willposesome questions ontheissues ofconsistency orlackofitintheEC's
handling ofthese andother veterinary drugs.
504. Before turning tothose questions Iwould liketoreview whatCanada submits arethepoints
ofconsensus between thePanel'sexperts: (1)good animal husbandry practice isabroad term
encompassinggoodherdhealth,managementpracticesandincludesgoodpracticeintheuseofveterinary
drugs; (2)intheevent thatgoodpractice intheuseofveterinary drugs isnotfollowed, higher residue
levels mayresult.
505. However, given thefactthattheMRL wasderived fromanADIwhere alarge safety margin
hasbeenapplied, suchanevent isunlikely tocause anadverse health effect; (3)consumers arenot
abletodistinguish themeat ofananimal treated withgrowth-promoting hormones andthemeatof
anuntreated animal; (4)observing withdrawal times forthehormones doesnotguarantee zeroresidues
inmeat. Noresidues detected doesnotimply thatthere arenoresidues present inmeatastheymay
bepresent atlevels thatarebelow detection; (5)following treatment withthenatural hormones, for
either therapeutic, zootechnical orgrowth-promoting reasons, hormone levels willfalltothosenormally
associated withuntreated animals. There arenodifferences between theresidues ofnatural hormones
thatareendogenous totheanimal andtheresidues ofthesame hormones administered exogenously
totheanimal. Extensive datarelating togenotoxicity andcarcinogenicity wereavailable totheJECFA
andwereconsidered bytheCommittee. TheCommittee concluded thatthefivecompounds evaluated
arenotgenotoxic carcinogens; and(6)growth hormones havebeenusedinanimal husbandry formany
years; insome cases upto40years andtherearenohuman epidemiological datathatsuggests ahazard.
Adverse health effects havenotbeenobserved inthose countries using growth hormones.
506. Ihavejustoneother point Iwanted toraisebriefly, notforpurpose ofresolution butrather
toalert thePanel toanadditional concern thatCanada has. Ithasbecome apparent thatthe
European Communities intend topresent aslidedemonstration atsome timethisafternoon. Ihave
notseenthatdemonstration andIdonotknow thecontents ofit,butIamconcerned thatitmaywell
befresh evidence which would beintroduced aftertheFebruary deadline thePanel hassetandIam
alsoadvised bysome people whoclaim tohaveseenthese slides thatitisoflittlescientific assistance
andmaywellbeinflammatory. Ifandwhen theECchooses topresent thatslideshow Iwould hopefully
haveanopportunity todiscuss whether itisappropriate ornot.
507. IfImayIwould liketoturntomyquestions.
508. Dr.Arnold, onpages 10to12ofyourwritten answers youdescribed theevaluations conducted
bytheECforoestradiol andprogesterone pursuant toRegulation 2377/90. Asaresult oftheevaluation
oestradiol hasbeenputintoAnnex 2ofthatRegulation andprogesterone ispending Iunderstand.
Could youdescribe thesignificance ofputting these substances inAnnex 2andcould youcontrastWT/DS48/R/CAN
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itwiththesignificance ofputting asubstance intheaccompanying Annex 4andperhaps describe some
ofthesubstances thatareinAnnex 4?
Dr.Arnold
509. Ishould perhaps spend thefirstminute describing theworking relationships between JECFA
Codex andthecompetent bodies oftheCommunity because Ithink thenyouwould better understand
howthishappened.
510. WehavesetupintheCommunity aworking party obliged topropose maximum residue limits
forresidues ofveterinary drugs in1984. Westarted atthebeginning without having atruelegalbasis
soitwasabigadvantage when Regulation 2377/90 became effective on1January 1992. Ifyoulook,
forexample, attheOfficial Journal, ormaybe atVolume 6oftheRules Governing Medicinal Products
intheEuropean Community, youwillseeawhole volume devoted tothisissue. Youwillseethe
regulation, youwillseeguidelines, whattherequirements arefortheevaluation andyouwillseean
annex tothatregulation withalistofstudies required inorder toscientifically evaluate thesubstances.
Thislistisabsolutely identical withthelistofJECFA requirements because ithaspractically been
copied from JECFA.
511. IwastheChairman ofthisSafety Group atthiscritical timeformore thanthree years and
washelping drafting theserulesandregulations atthattime. Thiswasalsoaninteresting timebecause
JECFA hadjuststarted doing reviews andwequickly realized thatthiscould beofgreat helptous
intheEuropean Community.
512. IfIlookbackatthetimebetween 1984 and1988-90 wehadnotachieved tosetanyMRL
because itisreally atedious procedure, andassoonaswewereabletocooperate withJECFA and
Codex andharmonized ourprocedures withasystem, wealsoharmonized withtheFood andDrug
Administration wehadregular meetings theECCommission andvarious experts withtheFood and
Drug Administration, there wasanexponential growth. Ifyoucheck thelistofMRLs wehaveso
faradopted itisquite aconsiderable list.Butyouwillfindtheexposure limits, theADI, arealmost
every timeidentical, those proposed byJECFA withthose usedintheEC.There areslight differences
intheMRLs andthiscanbereadily explained because veterinary practices arenotthesame inall
countries.
513. Coming tothehormones, when JECFA hasproposed MRLs andADIs forhormones itwas
impossible todiscuss thisissue inthisSafety Group andintheCommittee ofVeterinary Medicinal
Products because itiswellknown thatwehavehadalready atthattimethespecific agricultural policies
andthespecific rules. Therefore itwassurprising tome,andItoldyouyesterday, thatsixyears after
JECFA haddiscussed these substances, aCommittee oftheECcame tothesame conclusions thatthe
JECFA position isadopted andtheyalsofeltitwasunnecessary tosetanamount inADIforoestradiol
andwasunnecessary tosetanMRL andthishasbeensigned bythecompetent authorities ofDGIII,
ofDGVI, ithasbeenpublished intheOfficial Journal. Andthisdemonstrates that,scientifically spoken,
whatJECFA produces, what theJECFA Codex system produces, eveniftheresults havenotbeen
officially accepted intheCodex procedure theyareusedeveryday andtothebenefit oftheconsumer
protection inEurope.
514. Iwanted tosaythisatlength because otherwise youcould havetheimpression thatwefeel
veryuncomfortable withJECFA. Infacttheopposite istrue.
515. Coming backmore specifically toyourquestion Annex 2ismeant forsubstances which no
MRL isneeded. Igiveyoumaybe twoexamples. Ifyouusesometimes alocalanaesthetic onahorse
itmight benecessary tosetawithdrawal timebutthisisaridiculous problem inviewofsetting MRLs
forconsumer safety inacommunity liketheEC.Thiscould beacandidate forsuchasubstance, or
ifthesubstance absolutely harmless aftertheevaluation hadbeendone. Theusual procedure isthatWT/DS48/R/CAN
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thecompany hastoapply forinclusion inAnnex 2andtheyhavetosubmit scientific evidence. Harmless
substances,mainlyharmlesssubstances,forwhichthereisnoneedtosetanMRL,forexample,elements
which endogenously occur inthebody. Itisarather longlistandtheyareputintoAnnex 2.
516. InAnnex 4itisalittlebitmore difficult. Originally thisAnnex hadbeendeveloped toinclude
substances forwhich itisimpossible todevelop anyconditions ofsafeuse. Thismeans forreal
hazardoussubstances,thiswastheoriginalmeaning.Butwhatthenoccurredthatlaterwehadsubstances
forwhich there were indications thattheycould behazardous andgapsinourknowledge missing
information. Since these were alloutofpatent substances andsince nosponsor applied toprolong
thepresence ofthese substances onthemarket inorder tobeabletodevelop themissing data, some
ofthesesubstances havealsobeenincluded inAnnex 4.Thatmeans wefindtheresubstances forwhich
itisquite surethattheyarehazardous under allcircumstances andother substances forwhich there
isastrong indication thattheymight behazardous andnosponsor could beidentified whoiswilling
toproduce themissing data. Maybe thisisenough forthemoment from mypoint ofview.
Mr.Thompson (Canada)
517. Mysecond question isalsodrawn from some ofthematerial inDr.Arnold 'sanswers. By
wayofprelude Icanletyouknow itisacompound question andthere willbesome follow-ups that
come withit.
518. Inyouranswer toquestion 2.2onpage5ofyourwritten answers thereisatablethatdescribes
theusesofnature identical hormones andtheiresters intheEuropean Communities. Myfirstseries
ofcompound questions are: How arethese substances used? Why arethey used for
oestrus-synchronization andwhen usedforsynchronizing oestrus, aretheanimals treated because they
aresickorforazootechnical purpose? This question mayalsoventure intotheexpertise of
Professor McLean.
Dr.Arnold
519. Icannot satisfactorily answer allyourquestions andsub-questions. Iwanted toshow only
afewexamples ofsubstances forwhich Iabsolutely know thattheyareused. Thelistmight belonger
because alistofsubstances which areincompliance withourrules intheEChasbeensetupearly
ontheadvice bytheCommittee forVeterinary Medicinal Products, there aremore substances onthe
market. Iamnotaveterinarian soIcannot really tellyouwhether thisisjustified tousethesesubstances
forthispurpose. What Iwanted toshow youwashowsimilar some ofthese substances arewhich
areusedontheonesideforgrowth promotion andontheother sidefortherapeutic andzootechnical
purposes, butthere arealsodifferences intheesters, andbased onthistableIdeveloped myanswer
sothese were justexamples andIcanasanon-veterinarian notjustify theirusebutIamsurethey
areusedinaccordance withthedirectives intheEC.
Mr.Thompson (Canada)
520. Iwonder ifProfessor McLean oroneoftheother experts canassist mewiththatinformation?
Dr.McLean
521. Thank youMr.Chairman. Oestrus-synchronization isacommonly-used animal husbandry
practice. Yousynchronize thereproductive activity ofyourherdforavariety ofpurposes; itmay
relate totheavailability offeed, itmight relate totheavailability ofmarkets, etc.Itisarelatively
common animal husbandry practice.WT/DS48/R/CAN
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Mr.Thompson (Canada)
522. After usewould residues ofthese administered substances bepresent inmeatandmilkofthe
treated animal?
Chairman
523. Iwould suggest thatalloftheexperts maytakethefloor iftheywishtodoso.Whowould
liketogofirst?
Dr.McLean
524. Yes,theresidues would beinmeat ormilkiftheanimal wasslaughtered. Itisinteresting
thatoestrus-synchronization thatisoften usedindairy cattle inavariety ofproduction circumstances
andtheresidues would beinmilk.
Mr.Thompson (Canada)
525. IfIcould continue withthattableandsome oftheinformation onit.Iwonder ifanyofthe
experts whofeelconfident could helpmewiththeuseofthese various esters intheECformulations.
What arethechemical differences between theesters andwhyaredifferent esters usedandisthere
anycomparison ofpersistence inthebody ofthese various esters?
Dr.McLean
526. Theesters aregenerally usedtoaltertherateofuptake ofthedrugfrom either theinjection
siteorifitisinsome sortofintravaginal device forexample, although generally notthere, italters
therateofuptake. Butwhatgenerally happens isthattheoestradiol esterisactually metabolized either
atthesiteofinjection intheblood orinthetissue andthebond between theactive substance, the
oestradiol, andthesidechain towhich itisbound isreadily broken andtheactive constituent
oestradiol 17beta, ortestosterone initsvarious forms, istheactive constituent.
527. There canbeunder some circumstances small quantities oftheesterappearing intheblood
andthatispicked upbyanalysis. Butthose levels aresmall andnoconsideration when itcomes to
looking atthetoxicity because, forexample, ifthere were esters inthemeat andsomeone ingested
thatmeatthentheenzymes ofthegastrointestinal tractofhumans thatdigests normal foodreadily cleave
theesterbond.
Chairman
528. Mr.Thompson, justforthebenefit ofthePanel, would youanticipate todrawsome conclusions
from these statements? Iamnotinaposition todosomyself.
Mr.Thompson (Canada)
529. Ithoughtthatwasthepurposeoftomorrow'smeetingwhenIwouldbepresentingoralargument.
Butthegeneral purpose oftheselinesofquestions andafewothers thatIhaveistotryanddemonstrate
thattheEuropean Communities usesome ofthese hormones either alone orincombination for
zootechnical purposes suchasinincreasing therateofproduction insheep andcattle. Notwithstanding
thatother alternative means maybeavailable theycontinue tousethesesubstances forthese purposes.
What Iwould bearguing tomorrow inalikemanner isthatNorth America andother places usegrowth
hormones.WT/DS48/R/CAN
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Dr.André
530. Mr.Chairman, Ithink there isaverybigdifference between theuseofsuchdrugs for
therapeutical orzootechnical purposes. Inveryprecisely defined animals, asProfessor McLean said,
andtheuseofthesamehormones orsimilar hormones inlargescaleforgrowth promotion. Noscientist
hassaidthatitisabadthing tousethese hormones fortherapeutical use.Theproblem isforgrowth
promotion onlarge scales onalltheanimals, itisnotthesame thing asisbeing discussed now.
Chairman
531. Isittruethatfortherapeutical reasons thisisdone under prescription byassistance ofthe
veterinarian, while thegrowth promotion isnotdoneso?CanIaskthisjustformyclarification to
oneoftheexperts?
Dr.André
532. InEurope itisdoneunder veterinarian control. Directly byveterinarians insome countries
orunder veterinarian control byprescription inother countries. Forgrowth promotion wehaveno
experience.
Mr.Thompson (Canada)
533. Perhaps Icould continue withsome oftheother partsofmyquestion anditmaybecome clearer
astothereasons Iamasking this. Myunderstanding isthatitisnotsomuch therapeutic usesas
zootechnical usesinorder toincrease theproduction ofsheep andcattle sothattheirgestation periods
arereduced andhappen more frequently.
534. Cantheexperts helpmewith whether there areanysynthetic hormones used inthe
European Communities forsynchronization ofoestrus such asmedroxy progesterone acetate or
allyltrenbolone, orwhether oestradiol iscombined withprogesterone insome ofthese proceedings?
Dr.Arnold
535. Iwould liketoaskmycolleagues toassist me. What concerns allyltrenbolone there isan
exemption inthedirectives. Thissubstance canbeusedbecause, asIsaidyesterday, itisnotsuited
forgrowth promotion. Although thename issuggestive, itdoesnothavetheproperties oftrenbolone.
Allyltrenbolone istotally different fromtrenbolone withrespect tothebiological facts. Sothisisthe
firstpartofmyquestion.
536. ThenextpartIamnotsosure. Iknow thattheEuropean Medicines Evaluation Agency and
theCVMP hasjustfinished anevaluation ofmedroxy progesterone acetate under myrecommendation
andthisdoesnotfitintomypicture ofwhatislegalintheEC. Maybe you,François,youknow?
Dr.André
537. No,Ihavenoinformation ofthisregulatory point butinanycasethiscompound isusedfor
zootechnical purposes andnotforgrowth promotion. Itwillnever beevaluated byECOrganization
asgrowth promoters. Itisaverydifferent thing. Wearespeaking about things thatarenotofconcern
withgrowth promotion here.
Dr.Arnold
538. Myproblem isthatitissynthetic anditdoesn 'tyield thenatural hormone upon hydrolysis.
Thatismypoint. Itiscertainly notsuitable forgrowth promotion.WT/DS48/R/CAN
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Dr.McLean
539. Medroxy progesterone acetate issometimes included intoanintravaginal device along thelines
ofthesecond lineontable2.2ofDr.Arnold 'ssubmission. Itisusedinanumber ofcountries.
540. IfImight justaddforthesakeofclarification, whilst thesesubstances forzootechnical purposes
areusedinindividual animals, itisnotunusual insome practices forasignificant portion oftheherd
tobetreated overthelifeofareproductive season, ifIcould putitthatway.
541. Inother words, whilst individual animals aretreated youmight get10or15or20,Iamnot
fullyfamiliar withtheproduction procedures ofEU,oftheherdtreated overonepartoftheyearthat
isassociated withthebreeding season.
Dr.André
542. Mr.Chairman, maybeyouarenotveryfamiliar withthereproduction control infarmanimals.
Inthiscase, mayIexplain toyouthatthemedroxy progesterone acetate isincluded inasponge and
thesponge isputintothevagina ofthesheep withasmall cord. During aperiod between 10days,
15days, twoweeks ormaybe alittlemore butitisnotaproblem. Then thesponge ispulled outwith
asmall cordandthenafterthistreatment theanimal comes intooestrus andistheninseminated and
becoming pregnant inmost cases. Only onepercentfailtobepregnant andthismaybe could bea
problem fortheseanimals, butusually people tryagain anditisnotreally aproblem. Itisnotaproblem
ofresidue ofsynthetic hormones because these animals arebredtohavesheep andtheywillstaya
longtimeinthefarm. They willnotbeslaughtered aftersuchtreatment. Itisnottheobjective. It
isverydifferent totreating animals forgrowth promotion andtoslaughter themattheend. Itshould
beveryclear inyourmind.
Chairman
543. Isthisastepofpreventive medicine oristhisatreatment foranimals whohavedifficulties
toconceive?
Dr.André
544. Itisjustaso-called zootechnical practice. Thatmeans itismore easyforthefarmer tohave
allthefemales atthesame dateonoestrus andtoinseminate them atthesame timeandthentohave
products atthesame time. Itismore convenient formanagement ofanimals. Nomore.
Chairman
545. Butitisastandard procedure which isapplied tohealthy animals?
Dr.André
546. Itisfamiliar procedure. Itisapplied insheep mainly. More insheep Ithink thanincows.
Mr.Thompson (Canada)
547. CanIunderstand youtosay,Professor André, thatfarmers didittotheirwhole herds ata
single timeinorder toassist conception occurring atthesame time?WT/DS48/R/CAN
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Dr.André
548. Ifyourquestion istoknow iftheycanbuythisproduct freely, theanswer isno.Thisproduct
isalways under veterinary control.
Mr.Thompson (Canada)
549. Ihadnotasked thatquestion. MayIproceed withmynextquestion Mr.Chairman?
550. Again Ihaveasomewhat compound question. Inanswer toquestion 30ofthePanel concerning
thepotentialadverseeffectsonhumanhealthfromresiduesofcarbadox,monesin,olaquindox,avoparcin,
benzylpenicillin andcarazolol, ivermectin andorganophosphorus compounds, someoftheexperts noted
thatwhen usedcorrectly, theresidues from approved veterinary drugs should notproduce adverse
effects inthehuman population.
551. Inquestion 17ofthePanel theexperts wereasked toconsider theimplications forhuman health
ofresidues from themisplaced implants orimproper administration ofthesixhormones indispute.
AndIwonder iftheexperts could extend theiranalysis andcomment inrespect totheresidues ofthe
veterinary drugs Ireadoutandlisted inquestion 30,astowhataresome oftheimplications forhuman
health when theyaremisused inasimilar waydescribed inquestion 17?Forexample, could theexperts
explain whatadverse health effects mayresult ifahypersensitive person ingests meat ormilkfrom
ananimal thatwastreated withbenzylpenicillin, when therequired withdrawal period hasnotbeen
observed andtheresidues from benzylpenicillin insuchmeatormilkexceeds prescribed MRLs, as
anexample.
Dr.Arnold
552. Maybe Icanpartly cover thisquestion. Iamalittlebitreluctant tocompare thehormones
withcarbadox because bothsubstances havebeenregulated, orproposals havebeenmade byJECFA
concerning these substances, thatinbothcases ifgood practises areobserved there isnoappreciable
risk. SoIcould saytheyareequally safeifgoodveterinary practices areobserved. Because although
carbadox itselfisagenotoxic carcinogen, itissoquickly metabolized thatifgoodpractices areobserved
neither carbadox noritsmain carcinogenic metabolite ispresent asaresidue. Only aninnocent
metabolite quinoxaline carboxylic acid, which hasbeenextensively tested including carcinogenicity,
andthisisthecompound onwhich theMRL hasbeenproposed.
553. Ifsomebody doesnotrespect thewithdrawal timethere might beanincrease inthisinnocent
metabolite, butthecloser youcome totheadministration thereisanincreasing riskthatthecarcinogenic
compound itself oritsmetabolite ispresent. Forexample, atzerotimeofwithdrawal itisobvious
thatitwould bepresent andthatnowyouhaveadifferent quality ofriskandhowdoyoucompare
this? IfIamalittlebitreluctant andImustinsist thatitistheaimofourprocedures, tocheck whether
conditions ofusecanbeproposed which iffollowed guarantee thatthere isnoappreciable risk. And
ifthepossible riskisqualitative innature howdoyouprepare this? Thisisthefirstpartofmylengthy
answer.
554. Concerning benzylpenicillin, Ihadlooked carefully atbenzylpenicillin, Iwasconsultant to
WHO atthetimebenzylpenicillin hadbeenevaluated. What isinteresting toseeisthatabout 15per
centoftheworld population, some figures arehigher, other figures arelower, aresensitized against
benzylpenicillin. Butwehavecarefully looked atallthereported cases. Only averysmall number
ofcases onecandiscuss between fiveandtenbutinnowaymore thanten,havebeenobserved over
themany years ofuse.Billions ofdoses administered ofbenzylpenicillin tohuman individuals causing
sensitization butfewcases where residues werethecause ofanallergic reaction. Thelevels proposed
byJECFA ofbenzyl penicillin aresolowthatinthewhole literature youfindonlythree cases where
alower levelhascaused aneffect inahuman being. Thedairy industry needs these lowlevels tooWT/DS48/R/CAN
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because themostsensitive population inthiscasearethestarter cultures usedforyogurt production,
forexample. They aremuch more sensitive thanhuman beings. Sothehuman consumer benefits
fromthisthatthemixcannot beusedforfoodprocessing purposes ifitcontains highlevels ofpenicillin.
Chairman
555. Thank youDr.Lucier.
Dr.Lucier
556. Ihaveacouple ofquestions, before Iattempt toanswer thequestion. Socarbadox doesproduce
tumours inthelongtermbioassays inrodents, isthatcorrect? Andarethere multi-sites more than
onesiteofcancer intheanimals?
Mr.Thompson (Canada)
557. Idon'tknow ifI'mqualified toanswer thatquestion. Iunderstand thatit's11outof12sites;
perhaps ManSenYong cananswer thequestion forus?
Dr.Man SenYong (Canada)
558. Well, actually IthinktheJECFA hasdonetheconcrete evaluation ofthetoxicology ofcarbadox,
including thegenotoxicity andcarcinogenicity. Somaybe Iwould havetheJECFA persons toanswer
forthat.
Dr.Lucier
559. Letmeaskoneother question while youarelooking thatup.How are,inrelation to
Dr.Arnold 'sanswer, carbadox residues everfound inproducts consumed bypeople? Andifsoare
theMRLs exceeded from timetotime?
Dr.McLean
560. AnMRL wasnotsetforcarbadox andnorwasADIspecified. Andit'spermitted foruse
providing with asensitive regulatory method youcannot detect residues. It'sametabolite
desoxycarbadox that'scarcinogenic. It'sashort-term intermediate metabolite between carbadox and
quinoxaline compound. Andalsoquinoxaline-2-carboxylic acid, theend-metabolite, there were
carcinogenicity studies onthataswellastheintermediate desoxycarbadox. Soyouhavetheparent
compounddesoxycarbadoxandthefinalmetabolite.It'sacompoundthat'susedwidelyinsomecountries
including theEUandtherecommendation ofJECFA wasthattheycould notontheevidence presented
stateanADIoranMRL forgenotoxic carcinogenic.
Dr.Lucier
561. Soresidues arenever detected Iguess ofcarbadox?
Dr.Arnold
562. Ifthewithdrawaltimeisobservedwewillnotevenfinditquinoxalinicacidwithroutinemethods.
However, withmore sophisticated methods youcanshow thatupto70daysaftertreatment this
metabolite persists.WT/DS48/R/CAN
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Chairman
563. CanIbriefly justformyclarification nowaskthePanel whether theyconsider itpossible to
compare theuseofthehormones wearetalking about andthesubstances wewere justdiscussing,
youwerereluctant todoso.Could Ihavetheviews oftheothers whether thisiscoming intoacategory
where wecould really startcomparing theuse.
Dr.McLean
564. Iwilltryandshedsome lightonitMr.Chairman. When anADIsetforacompound, providing
thatADIisnotexceeded, thentheriskassociated withconsumption ofproduce containing thecompound
inquestion uptotheADIisessentially zero. NowIusetheword essentially toputting emphasis on
thefactthatzeroriskisnotanobtainable figure. However, ifyouexceed theADI, thenthenature
oftheriskvaries from compound tocompound. Forexample, ifyouseriously exceeded theintake
ofcertain compounds, thendepending onthistoxicological profile, youmaycause some quiteserious
effects. However, many oftheADIs aresetonarelatively minor change suchasabodyweight change
andchange inanorgan weight, some minor variations insome constituents ofblood. Sotherefore
toexceed theADIinthatcasewould notbeasserious. Andsowhatwedoiswedetermine alevel
where thereisnoobserved effect inthetestanimal systems, thenweapply asafety factor andbydoing
thatyouessentially reduce theriskofconsuming anamount equal totheADIonadailybasisforlifetime
tozero. However, onceyoubegin toexceed thatADIyouintroduce risk. Therateatwhich thatrisk
comes in,ifIcanputitthatway,andtheintensity ofthatriskvaries from compound tocompound,
depending onthattoxicological endpoint which made thenoeffect leveluponwhich youderived the
ADI. You'vegotafurther question Iguess?
Chairman
565. Dr.Lucier, onthiscomparison question.
Dr.Lucier
566. That'swhere Iwastrying togetsome information sothatIcould determine whether ornot
suchacomparison could bemade, interms ofatleastcarcinogenic risk. Ithink thatwhatDr.McLean
wastalking about wasnotessentially acarcinogenic riskthatwasahormonal activity risk. Sothey
aretwodifferent things, twodifferent methods toestablish risk,butIwasjusttrying todetermine
withtheinformation available ifitwould bepossible tocompare thecarcinogenic riskatresidues that
might benormally encountered versus theresidues thatmight benormally encountered from thesix
hormones inquestion.
Dr.Ritter
567. ButtheissueMr.Chairman, Ithink asanumber ofpeople havealready attempted toexplain,
isthatatpermitted residue levels, noneofthese compounds constitute arisk. That'sthenature of
theprocess ofestablishing anADIandsubsequently aMRL. Itpresumes thatthere canbelifetime
dietary exposure, every dayofyourlife,andthatcontinuous dietary consumption willpose, forlack
ofabetter termI'llsayessentially noriskatall.Thequestion thatyouareasking infactiswhatif
thatresidue levelisexceeded? Itgoesbeyond what'sbeenspecified intheregulation, orinternationally,
andIthinktheattempt that'sbeing made bywayofexplanation isthatitwould bepotentially misleading
tosuggest toyouthatthese riskscanbecompared, because theADIs thatwe'vereferred torepeatedly
arebased onentirely different endpoints. They canrange from something relatively innocuous, in
which caseifanADIisexceeded theconsequence would berelatively trivial. Andtheycanonthe
other handextend tosuchissues ascarcinogenicity, inwhich caseitwould bepotentially averyserious
consequence. Sotocompare thetwo,simply because theybothhaveanADI, presumes thatthatADI
hasbeenestablished onasimilar endpoint. Which isalmost never thecase.WT/DS48/R/CAN
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Chairman
568. Would youthink thatthefactthattheuseabove theADIlevels varies greatly alsoinduces
thepossibility tohavethem regulated differently?
Dr.Ritter
569. Ithink thenature, having beeninvolved intheprocess ofsetting ADIs bothnationally inmy
ownjurisdiction andparticipating intheprocess onaninternational scale, oneisleftwiththeimpression
thatthenature oftheprocess issuchthatthere isasignificant margin builtintotheprocess, thatin
factwillhavetheeffect ofcompensating forthatinanycase. Ibriefly alluded tosome ofthose
yesterday. Forexample theassumption is,oneoftheassumptions wediscussed yesterday, isthe
consumption of500grams ofmeat perday. Imean Ithink wecanallprobably agree thatinfirst
principles that'sanoverestimate. Andsotheriskhasprobably beenexaggerated inthecalculation.
Thatyouwillconsume thatriskevery dayofyourlifeandsoonandsoforth. SoIthink collectively
astoxicologistsinvolvedinthatkindofaprocess,wehavetheimpressionthatMRLsthataretemporarily
exceeded, occasionally exceeded, infrequently exceeded, arenotlikely toresult inasignificant health
consequence,becausethecalculationhasalreadybuiltinsomuchovercompensation,thattheseoccasional
transgressions arenotlikely toproduce anadverse effect. That'stheinherent nature ofthecalculation
itself.
Chairman
570. Isthisaviewshared bythePanel?
Dr.Lucier
571. I'mstillsearching forananswer tohelpme.Irecognize thatthecarcinogenic riskofthese
agents isverylow.Within thatrange ofzerotoverylow,ifIcould getinformation Icould saywhether
ornottheriskswere comparable forcancer. Now thisisthegenotoxic carcinogen, oneaccepts an
ADIisestablished notonthebasis ofcarcinogenicity forgenotoxic carcinogens itsonthebasis of
something else.
Dr.Ritter
572. Inthecaseofcarbadox Ithink Dr.Lucier, whathasbeenexplained isthatthere isnoADI
andthere isnoMRL, because itwastheconsensus ofthePanel thatreviewed thematerial thatasa
genotoxic carcinogen wewereunable toestablish whatwould popularly bereferred toasanacceptable
intake. Theacceptable intake isnothing.
Dr.McLean
573. Wewould notnormally setevenanendpoint based oncarcinogenicity, because generally
carcinogenicity occurs atmuch higher doses thanwewould setano-effect level. Iftheno-effect level
wasbased oncarcinogenicity, wewould lookatthecompound andaltersafety factors andother things,
oragain wemight notpermit it.Andsointhisprocess, inmanaging therisksthrough theADI, the
aimisreally tomake surethatyoudon'tendupwithcarcinogens, asaresult atleastofanimal toxicity
studies, inthefoodchain.
Chairman
574. Perhaps, Dr.Lucier, youmentioned twodifferent methods ofdetermining risks. Onewould
beforhormonal action andtheother forcarcinogenic effect. Itseems tomethatwehaveanestablished
method forthefirstoneandthesecond oneissomewhat newtothefieldhere. Could youelaborateWT/DS48/R/CAN
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alittlebitonthesecond method andhowyouseetheimplications inthatparticular fieldhere, in
particular when wetalkabout whether these substances canbecompared orbetreated alike andso
on.
Dr.Lucier
575. IfIsawthetumour dataforcarbadox, Icould establish alevelatwhich acertain proportion
oftheanimals gottumours, andasbestIcould, Icould extrapolate down intotheverylowlevelrisks
whatpeople might beexposed to.There would havetobesome residues leftofcarbadox, justmaybe
notdetectable, there havetobesome residues left. AndIcould compare thatcarcinogenic riskto
thatfrom oestradiol oranyofthese other hormones inquestion. Now, that'sacomparative riskof
carcinogenicity thecomparative potency inwhatpeople ingest from500grams ofmeataday.Sothat
would beadirect comparison. Iwould havetoassume whatcarbadox levels existandthatwaswhy
Iwaswondering howoften theyaredetected infactinmeatsamples, ifever, andwhatthelimits of
detection would be.Then Icould take, youknow, something below thelimits ofdetection ofwhat
people areexposed toanddothecalculation onarough estimate withconsiderable uncertainty but
atleasttoseeifthecarcinogenic potency isinthesame ballparkornot.That'sallthatI'mafter.
Chairman
576. Issuchdataavailable ornot? MayIasktheexperts?
Dr.Arnold
577. Ihavenever seenpositive results andIseeresidue monitoring datasince many years. But
ithasnotbeenintensively monitored ontheother side,thatistheother difficulty. ButIcould perhaps
saythatatleastintheCommunity itisonlyusedinpiglets uptoamaximum ageof4months, soit's
quite realistic thatthewithdrawal times areobserved andthenthere isnocarcinogenic residue inthe
tissues, justmaybe atrace ofthisinnocent metabolite.
Dr.Lucier
578. Iwon'tbelabour thisanymore afterthisonepoint. Ifapparently there istumour datathat
issummarized, ifIcould lookatthatsometime during theafternoon I'lldomylittlecalculations.
Myintuition tellsmethattherisksaregoing tobesimilar, carcinogenic risks.
Mr.Thompson (Canada)
579. I'madvised thatthere mayberesidue datafordesoxycarbadox, butperhaps ifIcould restate
thequestion. Ithink wearenotcoming directly withwhatIwasgetting at,wehaveheard statements
and,IthinkDr.Ritter wasdrawing attention tothefactthatwhen JECFA andCodex review andapprove
things andsetstandards itisassumed thatthere isnoriskassociated withanyofthese substances, any
ofthesixhormones atissue, orcarbadox, orcarazolol orthebenzylpenicillin. Theexperts hadbeen
asked tospeculate ifthestandard administration procedures areabused inrespect tohormones and
proper procedures arenotfollowed, isthere apossibility ofacarcinogenic effect. Andwehaveheard
thatinrespect ofsome ofthehormones theanswer was,while close tozerorisk,yes.AndI'vebeen
asking inrespect tosomething likecarbadox, which hasalsobeendescribed asgenotoxic carcinogenic,
where anMRL andanADIcannot besetbecause ofit,ifwetakethehypothetical situation where
ithasbeenabused, administration hasnotbeenproperly followed, canwedrawthesame conclusions?
Ortoputthematter another way,istherearational reason todistinguish between permitting substances
which aregenotoxic carcinogenic islikecarbadox andpermit theiruse,while imposing atotalban
onhormones which aresaidtohavenorisk,verging onzeroaswell?WT/DS48/R/CAN
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Chairman
580. Whowould likethefloor?
Dr.Arnold
581. Since youareasking fordata,maybe fortherecord Icould tellyouwhatwehaveseenatJECFA
when pigswere treated withcarbadox. Theresidue level ofthis,Icallitinnocent metabolite,
quinoxaline carboxylic acidwas18.9micrograms perkilogram at30dayswithdrawal; was5.5
micrograms perkilogram at45days, 1.3microgram perkilogram at70dayswithdrawal.
Chairman
582. Thisgoestotheprevious question. Would youcome backonthefigures here?
Dr.Lucier
583. Iactually dohavethetumour data. Carbadox isapretty potent carcinogen interms ofmultisites.
Sotheanswer toyourquestion isyesifimproperly usedandthere were residues itwould posea
carcinogenic risk.
Mr.Thompson (Canada)
584. Andjustbefore weleave thatperhaps Icould askDr.McLean toexpand onhisanswer to
question 11where hediscusses organophosphorus compounds andthehealth effects there. Perhaps
Icould askhimtocomment oncarazolol which Iunderstand isusedfortransporting pigsimmediately
priortoslaughter andthecomparative withdrawal periods, andwhether there areanyrisksassociated
withtheuseofthatdrug.
Dr.McLean
585. Inrelation totheorganophosphorus compounds, theyarequitepowerful neurotoxins inhumans
andinanimals, andareusedgenerally tokillinsects although there areother usesforthem suchas
removing foliage fromcertain crops. There aretwoproblems withthem, oneisdelayed nerve damage
andthatisgenerally aresult ofdirect exposure ofoperators andthelike. However, under some
circumstances residues incrops inexcess oftheno-effect levelhavecaused problems, acute problems
oforganophosphorus poisoning. Andsome ofthem arecarcinogenic andsotherefore safety factors
toremove thecarcinogenic hazard intheappraisal, that'sbeentaken intoaccount although, generally,
thesafety limits arebased onacute effects thatthepoisoning effects thatyousee.Buttheyhavebeen
associated withpoisoning associated withexceeding theMRL. Inrelation tocarazolol, carazolol does
haveaneffect oflowering blood pressure andheart rate,it'srelated tothedrugs commonly usedin
human tocontrol blood pressure andheart rate. Itisalsousedtoprevent aspecific form ofstress
inpigsduring slaughter. Andofcourse pigsaresentfrom thefarmdirectly toslaughter generally
andifyouaregoing tohaveaneffective treatment forthestress associated withtransport, thenyou
havetotreatthemjustbefore transport sothatthedrugiseffective during thetransport process. And
there hasbeenconcern thatifpeople were toingest carazolol atthesiteofinjection thentheymay
getadosewhich could haveeffects onheart rateandblood pressure. Thesensitive human population
thatwastaken intoaccount inthisassessment arethose people already under treatment withthisgroup
ofagents forthecontrol ofblood pressure andassociated cardiovascular disorders, andifonewas
tosuperimpose adoseofcarazolol ontopoftheexisting medication thenthere could beaproblem.
Sothese twocompounds invarious ways, iftheADIisexceeded cancause difficulties.WT/DS48/R/CAN
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Mr.Thompson (Canada)
586. Justaquick follow up.Aretheorganic phosphates everusedinanimal production?
Dr.McLean
587. Theyarecommonlyusedinanimalproductiontokeepundercontrolinsectsonanimals,relatively
widely used.
Mr.Thompson (Canada)
588. Yesterday theEuropean Communities quoted fingers, sorry figures, onthenumber oftests
theydoforresidues ofhormonal substances. Weunderstand thatProfessor André 'sexpertise isin
theresidue testing. Henoted thattheEChasdeveloped multi-residue tests. AndIwonder,
Professor André, could youdescribe whatsubstances theEuropean Communities testforandcomment
onhowmany ofthese testscome backpositive andforwhatsubstances?
Dr.André
589. Icangiveyousome comments inthefieldofmycompetence, thatmeans onhormones, on
thyrostatic compounds andonbetaagonist compounds. Concerning thefirstpartofyourquestion
Icannot giveyouacomplete list,sotoday ofallthexenobiotic compounds which arelooked forin
arealmulti-residue analysis, butyoucanimagine thattheyinclude progesterone, nandrolone, oestradiol
andmanyothers,usually30differentcompoundsarelookedsystematicallyfor.Concerningthethyrostat
theyarejustabout 6compounds usually, small compounds, andtheyareallofthesame groups and
derivatives ofuroside compounds, true-uroside compounds. Andconcerning betaagonists theclassical
research includes nowsomething astendifferent compounds fromclenbuterol anditsgroup, Imean
manbuterol andothers andsalbuterol aswellasractopamine andmany others. Allthese compounds
havebeenbanned inECandwearelooking forpotential misuse ofthese compounds. Thelevelof
detection ofthisresearch isveryimportant toconsider anditsalways below 2ppb.andsometimes
reach more sensitive levels assome 10or20ppb's.forlooking atresidues inmeat specifically.
Concerning thesecond partofyourquestion, interms ofpercentage ofpositive results Icannot answer
thisquestion asascientific people andthenumbers Icangivetoyouwould bewrong numbers for
different reasons. Thereason ispersonally Iamincharge ofanofficial national laboratory andIhave
more positive thanusual because Iconfirm results ofother laboratories. Thisquestion hastobeasked
toofficial bodies ormaybe toourrepresentative ofofficial Community reference laboratories butnot
tome.
Mr.Thompson (Canada)
590. Iunderstand Dr.Arnold might beaware ofresults oftesting ofresidues ofhormonal substances
intheECandinparticular astudy ortesting doneinBelgium. Could youhelpuswiththatDr.Arnold?
Dr.Arnold
591. Ithink FrançoisAndré made agood suggestion since theresults oftheresidue testing inthe
EUaregiven toallreference laboratories. It'sagood suggestion thatmaybe someone from these
laboratories answer thequestion. Ontheother hand Ialsoseethese results onaregular basis and
I,what Icansayissomething thatIhavealready saidyesterday, wehavetodiscriminate between
random sampling which gives youamore relevant picture andsampling ofsuspect animals. AndI
saidyesterday already andIwould liketoconfirm this,ifwetaketheresults ofrandom sampling it's
notsobadthepicture. Inthemajority ofthemember States youfindnothing. There aresome member
States, Iwould notname themember States, butthere aresome member States where invealcalf
there seem toexistproblems, mainly withthenatural hormones. Ifwegotosuspect sampling thenWT/DS48/R/CAN
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thepicture istotally different, thenwehavemember States where wefindtrenbolone, zeranol, where
wefindprotestosterone, sometimes justafewsamples, sometimes ahigher amount. Butthishigher
figure isnotrepresentative forthesituation because thisthensometimes arefollow upanalysis, so
IhopeImade clearwhatmypoint is.Based onrandom sampling thesituation seems toberelatively
okay, withtheexception ofvealcalves insome countries. Based onsuspect sampling, wefindall
30things sometimes insome samples.
Dr.André
592. MayIaddjustashort complement tothese twocommunications. Firstofall,itsclear that
allthecompounds Ispeak about arenotlooked forinanyother countries asinEC. Andwhen we
discover some misuse ofsuchcompounds, usually andquite systematically Ithink, themeat isnot
delivered tohuman consumption.
Mr.Thompson (Canada)
593. Yesterday weheard quite abitofdiscussion concerning hormone levels andIwould liketo
clarify withtheexperts whatisaphysiological range andhowthatrange isdetermined andwhatcontrols
thatrange. Inparticular Ibelieve Dr.Liehr cautioned usthatpermitting theuseofgrowth-promoting
hormones inmeatmight upset thebalance ofhormones inahuman ingesting themeat. Cantheexperts
describe whatthebalance ofhormones inthebodyis;isitfixed ordoesitchange onadailyorweekly
basis? Andifhormones areadded directly toahuman, whateffect doesthishaveonthathormonal
balance? Perhaps some comparisons between theubiquitous 500grams ofmeatandacouple ofeggs
oraglass ofmilkwhich arealsoingested onaregular basis would beauseful comparison.
Dr.André
594. Concerning thebalance ofhormones weneedtomaybe aweek fordiscussion toexplain what
isnowknown about theinter-relations between hormones andthecomplex feed-backs phenomena and
soon.Justtohaveanideaoftheeffect ofinjection ofhormones tohuman beings, it'swellknown
Ithink thatbody-builders orsportsmen whoareusing hormones asanabolizing agents, withhigher
doses asusually usedingrowth promotion it'sclear, butthese people havealways laterverymany
problems interms ofreproduction andsterility itsclear. Thatisoneideatoillustrate what cana
hormone doinhuman beings.
Dr.Lucier
595. Iagree withwhatDr.André said. Thehormonal situation inyourbody ischanging aswe
speak. It'schanging inmybody, yougetnervous yourglucocorticoids goup,thatdoesother things
toyou,sotheyareconstantly changing, inconstant stateofflux. Howeachofthehormones regulate
eachother isnotanentirely known fact,infactitsnotreally known atall,except thatthattypeof
balancedoesoccur.There'stremendousinter-actions,crosstalkaswecallit,betweendifferenthormonal
systems. When thisisdisrupted there canbeawhole cascade ofevents which could result inchanges
inbiology andpotentially adverse effects. After having saidthat,theamount thatonewould takein
from sayifwecome backtotheexample of17betaoestradiol ineating 500grams ofmeat aday,
youbasically takeinonemolecule ofoestrogen ifyouwereawomen toevery 280,000 inyourbody.
Sothechances thatthatwould cause anendocrine disruption isprobably veryveryslight, remarkably
close tozero. Ifyouareamanyourlevels would beone-fifth thatsoitwould beonemolecule to
every 50,000 molecules orsomething likethis,sothechance thatthatwould cause initselfanendocrine
disrupting event isofcourse highly unlikely. There 'snodoubt thatit'scausing endocrine disruption
intheanimals thatarereceiving it,that'swhytheygrow because theirhormone system isdisrupted
andmodified andthebalance ischanged. It'saquestion ofamount.WT/DS48/R/CAN
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Dr.McLean
596. Justbywayofillustration ofthevariation, ifpeople want toturntotheattachment ofmy
submission, youwillseetheenormous ranges inpregnant cattle, orincattle ofprogesterone, oestradiol
andtestosterone; theranges andthevariations e.g.inpregnant cattle inmuscle forexample, thelevels
are10,000 nanograms perkilogram plusorminus 6,600. Enormous variations. AndIthink thatjust
reflects theindividual animals andsoit'sterribly difficult totiethisdown absolutely andprecisely.
Chairman
597. Imean averypopular comparison alluded to,theegg,theamount ofhormones youeatwith
aneggandthenit'scompared towhat youeatwhen youhaveanintake ofhormone treated meat.
Isthatacomparison which canbedoneandcould youelaborate onthis?
Dr.Ritter
598. WellI'mthinking wecould andinfactanumber ofresponses contain thatdirect comparison.
Thesteroid levels would becontained inaglass ofmilk, forexample. Thesteroid levels thatwould
becontained inafeeding ofbreast milktoanew-born infant would bethousands oftimes higher than
whatonemight expect inasteak orahamburger. Butifyouwould likeamore precise number I'm
justgoing to.
Chairman
599. Itisjustwhether onecanmake these comparisons, whether theyaresound.
Dr.Ritter
600. Ithink whatI'mintimating Mr.Chairman, isthatonereally can'tbecause theyareindifferent
worlds...
Chairman
601. ...Youcan't...
Dr.Ritter
602. Letmeputitanother way. Onecanphysically make those comparisons, thenumbers are
available. Butthere isnobasis forcomparison. Thesteroid levels associated withaglass ofmilk
orhuman breast milkoranynumber offoods would bemany many many times greater...
Chairman
603. ...Yes,butthese arethesame steroids?
Dr.Ritter
604. Exactly thesame. Wearetalking orders ofmagnitude difference interms ofthedimension
vis-a-vis thelevels ofexposure fromahamburger resulting fromananimal thathasbeentreated, when
compared toaglass ofmilkthatyoumight havefrom ananimal that'snever beentreated atall.WT/DS48/R/CAN
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Dr.Arnold
605. Mycolleagues havelimited theirstatements totheidentical molecules. Ifwewould addto
those identical molecules other naturally-occurring hormones infoodwhich haveadifferent potency
maybe lesspotent, buthaveoestrogenic action forexample, thenwewould discover thatinmany kinds
ofnatural foodincluding plant origin wefindsuchactivity. Thesteroids andtheirderivatives, asI
saidyesterday, wereverysuccessful inevolution. So,evenifyougodown tomolluscs toseaurchins,
youfindthese substances, youcan'tescape eating these substances, orsimilar substances withrelated
biological potential every day.So,there isnowayevenifyoudecide tocastrate yourself, inaddition
tostarve todeath, toescape these hormones.
Dr.Ritter
606. Mycolleague Professor McLean points outthatinthesecond submission oftheUnited States
(28October 1996) thatsortofcomparative table, Ihavepersonally notverified eachoneofthese
numbers, butthatsortofcomparative tableisinfactispresented onpage4.Theintake ofoestrogen
oroestrogenic equivalents ranges from tensofthousands inthecaseofsoyabeans; thecaseofin
anegg,youreferred toaneggas17,015 nanograms, andwhen wearelooking atanoestradiol implanted
steer, levels thathavebeenestimated aresomewhere intheorder of11nanograms. Aglass ofmilk
might represent 75nanograms inthistable, cabbage 24,000 nanograms. Iemphasize thatthese are
oestrogen equivalents because insome cases itisoestrogen directly, inother cases these willbewhat
issometimes referred toasphyto-oestrogen which arecompounds which arenotquite oestradiol but
areknown tohaveanactivity thatiswhatwesometimes refertoasanoestrogen mimic, it'sanoestrogen
want-to-be. Zeranol isinfactproduced forexactly thatpurpose. Itisnotoestradiol directly, butit
isclearly, itisproduced asaresult ofafungus, butithasanaction which issosimilar tooestradiol
although thepotency issomewhat different, thatwecallitanoestrogen.
Mr.Thompson (Canada)
607. Justtofollow uponthatalittlebit,asisobvious toevery oneI'mnotascientist andsimple
examples helpme.Someone hassuggested anexample fordealing withphysiology istocompare it
toathermostat inahouse where thereisarange oftemperature thatiscontained andwithin thatrange
arenormal things thatoccur, andthetemperature mayvaryupanddown butthat'sanormal occurrence.
Andwhen onedrinks milkoreatseggsorconsumes cabbage therewillbeanincrease within thatnormal
physiological range. Oneofthethings Iwanted tofollow upon,andperhaps Dr.Lucier canhelp,
ashedrew thecomparison withthe500grams oftreated beefofonemolecule from 28,000, by
comparison areyouabletohelpuswithhowmany molecules per28,000 wemight findwithaglass
ofmilkinapre-pubertal boy,theglass ofmilkforbreakfast?
Dr.Lucier
608. Justsayyoung boy! tosavefurther embarrassment!
609. Nowthenumbers formilkIhavearealittlebitdifferent. Ihavethem for17betaoestradiol
andtheyarealittlebithigher thanwhatyouseeinmuscle tissue, Ihavenowaytoknow, sinceIhaven 't
donethemeasurement myself, which numbers areaccurate. These things ashasbeenstated before,
arepresent inmilkandvirtually everything weeat,oestrogen. So,yougetanoestrogen loadinaddition
toyourendogenousoestrogenfromanumberofdifferentsources.Notonlythenatural17betaoestradiol
fromwhatyoueatbutalsofromthephyto-oestrogens andthefungal oestrogens thatwerealready talked
about. There 'saconsiderable amount ofphyto-oestrogens insoyaproducts especially soyaoil.So
weareexposed toalotofdifferent kinds ofoestrogens justfromday-to-day living thatareexogenous,
notproduced byourownbody. Itwould beverydifficult formetototalthem allupandthat'sone
ofmyactual research interests totryanddothattoseewhatthebodyburden oestrogen thatweencounter
from day-to-day living from exogenous sources, togetsome ideawhat theriskofvarious kinds ofWT/DS48/R/CAN
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disease might bebecause ofthose exogenous sources. SoIcannot giveyouaverygoodanswer except
tosaythiswould onlybe,theamount onereceived fromeating 500grams ofmeat, would berelatively
small compared totheother sources ofexogenous oestrogen onereceives.
Dr.André
610. Mr.ChairmanmayIgiveyouanotherexampleofhormoneinteractions,inrelationtothequantity
ofhormones inorder justtoillustrate whathasbeensaidpreviously. Wehaveknown hormone the
name iscortisone which hasvarious properties andanti-inflammation properties. Andwehavealways
asecretion inside ofthese compounds. When youhave, forexample, anacute inflammatory process
thephysician willgiveyouahighdosage ofexogenous orsimilar compounds ascortisone, forexample.
Andthenyourownsecretion willdecrease dramatically inplace oftheexogenous compound butafter
thismaybe aweek lateryouwillnomore needthe....... [tape ends]
611. Forachronic skindisease youwilltakevery, verysmall doses ofthesamecompound, cortisol
orcortisone oranother one,andyourownsecretions willdecrease very, veryslowly. Butifyoutake
these verysmall compounds asdrugs during months, andthenwhen youwillstop, youwillnever
recover yourownsecretions. Itwillhavestopped definitely.
612. That'sthedifference between anoccasional useandapermanent use.
Chairman
613. What willbetheconclusion?
Dr.André
614. Wecannot compare thefood intake ofdrugs orhormones inmeat occasionally, orthe
consumption ofapregnant cow,beefforexample, which cangiveyoualotofhormones andthesmall
amount ofhormone foodintake forallthepopulation during months andyears. Itistwoverydifferent
things.
Dr.McLean
615. IfIcould giveyouanother example, asamalecontraceptive agent, malehumans aregiven
testosterone,whichbyfeedbackmechanism,inhibitstheproductionofsperm.Thisformofcontraception
inhuman males isbeing trialed atthemoment. Inother words, youaregiving extra testosterone and
thepituitary gland sends amessage down thatthere istoomuch testosterone andshuts offthenatural
production, butatthesame time, itshuts offsome ofthehormones associated withsperm production,
andrenders theindividual temporarily sterile. Andofcourse onceyouremove thetestosterone being
administered tothemale, thenitallcomes backtonormal. Thatistherapy thatisundergoing trial,
atthemoment, inanumber ofcountries oftheworld.
Chairman
616. CouldIjustcomeinwithonequestionwhichpuzzlesme?Whenweseethesenaturally-occurring
highexposures inmilkoreggs, howdoesthatrelate tothecancer research weheard yesterday? Is
theriskthatisbeing assessed today where wehaveseensome thesis onit,isthatequally valid for
thisnaturally-occurring intakes every dayoristhere something special when wetalkabout growth
promoters? Could Dr.Lucier perhaps elaborate?WT/DS48/R/CAN
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Dr.Lucier
617. LetmedothebestIcanonthat. Ifyoustartoutwithapre-menopausal woman andher
oestrogen levelwhich ofcourse isveryhigh, thisresults byatumour-promoting mechanism, andI
don'tthink Ineedtogointothatatthispoint, inabout onewoman getting cancer inevery ten.So,
outofevery tenwomen intheirlifetimes, oneofthem willgetcancer. Andthat'sprimarily the
consequence ofhernaturally-occurring oestrogens. Andthat'sthepoint, andI'vemade alotof
comparisons throughout thismeeting.
618. Ifyoulookatthebeef,eating 500grams ofbeef,youwould getonemolecule forevery 28,000,
thepre-menopausal woman normally has,andonecould estimate acancer riskbased onthat.
619. Ifonesaysthenfromother sources, besides beef, there isahundred molecules, andI'mjust
pulling thatnumber outoftheair,butsayit'sahundred, andthat'sprobably aconservative estimate.
Then, thatwould contribute ahundred molecules andsothecancer riskfrom allother sources of
exogenous oestrogens would beahundred times thatwhatitisinbeef,fromagrowth promoted animal.
620. Sotheriskwould bevery, verysmall. Eating meatfrom agrowth promoted animal would
onlyrepresent asmall fraction ofthetotalcancer burden caused byexogenous oestrogens, notnormally
produced bythebody. Again, it'simpossible togiveaprecise number forthereasons Isaid,because
there isavastnumber ofenvironmental oestrogens outintheenvironment andweonlyknow about
afewofthem. Wecertainly don'tknow about allofthem.
621. Ithinkmyconclusion would bebased ontheassumption thatalltheoestrogens areacting alike,
thattheyallinteract withtheoestrogen receptor andstimulate thesame battery ofgenes asa
naturally-occurring 17betaoestradiol. That'scertainly trueforthemore potent oestrogens, some of
thefungal oestrogens, some ofthephyto-oestrogens, these kinds ofthings. They activate thesame
kindofgenes sothereisareasonable scientific foundation, formyconclusion, although there issome
uncertainty init.
Chairman
622. Mr.Thompson.
Mr.Thompson (Canada)
623. Professor André, there areacouple ofquestions Ihaveconcerning some ofyouranswers to
thePanel andIamhoping youcanclarify them forme,inparticular, youranswer toQuestion 2.
Youstateinpart:
"Ontheother hand, ifthephysico-chemical ororganoleptic criteria areconcerned bythis
question, andthequestion ofmeat quality canbediscussed, significant alteration ofeating
quality, Lowman etal,andsignificant lossoftenderness, Gerkin 1995, ofmeatproduced with
various implants haveactually beenreported."
624. When wegotothesource ofLowman, thestatement doesnotseem tobesupported. Icould
readfrom page48oftheLowman Report. Itsays:
"With regard tothecomposition ofthecarcass andthemeat, itwasapparent thattheuseof
thehormone implants affected areduction inthepercentage ofcarcass fat,anincrease inthe
percentage leanandamarginal decrease ineating quality..."
asopposed toasignificant alteration, asmentioned inyourquote. Itgoeson:WT/DS48/R/CAN
Page357
"...andanincrease intheproportion ofsaleable meatforbothheifers andsteers."
625. Inrespect oftheGerkin Article, where youhave indicated theGerkin article identifies a
significant lossoftenderness, atpage3323 oftheGerkin Article, theauthor states:
"Results ofthepresent study suggest thattheuseofsingle implants containing oestradiol, TBA
orthecombination ofoestradiol andTBA, hadlittle appreciable effect ondeposition of
intramuscular fatoronbeeftenderness."
626. Canyouhelpmewithhowthese articles support yourstatement?
Dr.André
627. It'sclearthatIhavenotinvented thisassertion andthattheyarealsoinside. When yousee
onlyLowman abstract, inthelastsentence. Itsays:
"...with marginal reduced eating quality."
Thatmeans thatthere isasmall reduction ofeating quality butthere isone.
628. Ifyoudiscuss about thedifference between significant andmarginally, marginally canbe
significant, statistically! Sorry, butstatistically, itcanbesmall, butsignificant!
Mr.Thompson (Canada)
629. Ialsohadaquestion about Question 6A.
630. Thisisdealing withwhether thereisanymore recent scientific evidence available withrespect
totheeffects onhuman oranimal health oftheuseofthesixhormones indispute, especially when
usedforgrowth promotion purposes, other thantheevidence already taken intoaccount byCodex.
Andyoustateasfollows:
"Concerning human health, there isadiscussion onthedecrease ofhuman sperm counts"
andyouciteNimrod andBenson:
"Anapparent increase oftheincidences ofhormonally mediated diseases likebreast cancer
andendometriosis andthedecrease inthemale/female ratiowhich arethought tobedueto
oestrogens intheenvironment. Whether theuseofhormones forgrowth promotion is
contributing tothisornot,cannot bescientifically proven, atthepresent time."
631. When Ilookatthesource, namely Nimrod andBenson, itappears thattheconclusion that
sperm counts havedeclined, isinfactcontroversial. Andtheonlyreported decrease inhuman sperm
count refers tocounts ofmeninParis, overthepast20years, which iswithin theEuropean Community
andunlikely tobedirectly related toeating hormone-treated beef.
632. Canyouhelpmewiththecorrelation between thedecrease insperm andthesexhormones
atissue forgrowth promotion here? Thisquestion isaddressed toDr.André.
Dr.Lucier
633. Thesperm count issueiscontroversial. Some people feelthatsperm counts intheindustrialized
world aregoing down, other people feelthattheyarenot.Andthereisalotofmethodological issues,
without going intothedetails, thatarecreating thecontroversy.WT/DS48/R/CAN
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634. Thedecreased sperm count hasbeenreported inmore thanonepublication, however, butthat
hasnotremoved thecontroversy inthislegitimate scientific debate. ItisnotonlymeninParis. For
example, meninCalifornia onlyhavehalfthesperm asmeninNewYork. I'mnotsurewhy! The
meninNewYork areveryproud.
635. Itisaveryacontroversial issue. There aredatafrom experimental animals thatshow that
neonatal exposure tooestrogenically active agents doescause adecrease insperm count, laterinlife,
inthemaleoffspring, andthere areplausible biological mechanisms forthat.
636. Butagain, thequestion ofwhether ornot,theamount received, Ithink itishighly questionable
thattheamount received ineating beeffromhormone treated animals would benecessary toproduce
that.
Dr.Ritter
637. Tocontribute something perhaps tothedebate here, Ithink mycolleague, Dr.Lucier puts
itquiteaccurately. TheFrench datathatwasreferred toamoment ago,waspublished byPierre Roget,
Ibelieve in1992, intheBritish Medical Journal. Itwasthefirstofsubsequent reports thatwereto
come popularizing theissue ofdeclining sperm counts. There were subsequently significant
methodological issues identified inthatreport, nottheleastofwhich werethatmany ofthese subjects
originated frominfertility clinics orsperm banks! Consequently, Ithink itwaswidely recognized that
thismayhavebeenaninappropriate sample tousetoexamine declining sperm counts, orforthatmatter,
anything related tosperm.
638. Ithink Dr.Lucier putsitquite accurately, when hesaysthatthisisverymuch anemerging
areaandIthink thebestthing orthemost accurate thing thatonecansay,isnothing atall,because
onecanfindasmany reports infavour ofadeclining sperm story, asonecanfindopposed toit.As
amatter offact,theNewYork datathatDr.Lucier referred toamoment ago,wasrecently reported
byHarry Fish, whodeclared NewYork mentohavethehighest sperm counts intheUnited States,
butnohigher thanNewYork menhavebeenforthelast25years.
639. Thepoint thatDr.Fishwasattempting tomake isthatitwould beinappropriate tocompare
NewYork menwithCalifornian men, butrather youhavetocompare NewYork menwithNewYork
men,California menwithCalifornia men,because therecanbemany variables thataffect sperm count
within ageographic region. Ithink thatthepoint thathewastrying tomake isthatitisinappropriate
tocompare across widegeographic regions, thebottom linebeing thatitiscertainly anemerging area,
butoneabout which theonlycertainty iscomplete uncertainty!
Chairman
640. Would youliketotakethefloor?
Dr.André
641. Ireadthispaper onemonth agoandIcannot findexactly thesentence butIamsuretofind
before thisevening something sointhispaper. Ithink youreaditalso,sowecanagree attheend
ofthissession thatthere issomething.
642. Youcannot saythatthesperm elaboration isnotunder hormonal control, that'sclear. And
youcannot alsosaythatsome alkylphenol ethoxylates haveaverydramatic effect onsperm elaboration
inmenandthatthese compounds havealsosome oestrogenic effects. That'sclear ornot?WT/DS48/R/CAN
Page359
Dr.Ritter
643. With respect, I'mnotsureitisquite asclearasperhaps youfeelitis.Thenonyphenol and
other ethoxylated compounds, Idon'twanttogetintoasidedebate here, butthere areanumber of
authors whohavepublished reports indicating thatwhen compared toE2,interms oftheiroestrogenic
potency, theyare10,000 times lesspotent. Thatorder ofmagnitude. Infact,oneauthor suggested
thatifwewere tocallnonyphenol oestrogenic, there would befewsubstances thatwould notbe
considered oestrogenic, onthesame scale.
644. ButIthink toputitmore correctly, intoperspective, Ithink asDr.Lucier indicated, there
havebeendramatic increases inbreast cancer which appear togobeyond those increases thatcansimply
beattributed totheintroduction ofmammography, particularly intheindustrialized world. There have
beenincreases inprostatic cancer, theorigin ofwhich seems tobeatleastinthefirstinstance, related
insome significant measure totheintroduction ofprostatic specific anogen. Forthose menintheroom
whoareover40,you'llknow theexperience verywell.
645. Theinterest inapotential roleoftheenvironment inbreast cancer, Ithink, stems from the
fact,thatwhen weaddupalloftheknown riskfactors forbreast cancer, weinclude theageoffirst
pregnancy, thenumber ofsuccessful pregnancies, thenumber oflactations, theduration ofthose
lactations, allofthose things thatweknow areimportant riskfactors inbreast cancer. Wecan'taccount
forallofit,andconsequently there hasbeenaninterest inthescientific community tolookforother
things thatmaybeinfluencing thedisease.
646. Ithink itwillbesome time. Certainly, Idoubt verymuch inmylifetime, where wewillbe
abletodemonstrate acleardefinitive roleforaspecific environmental substance. Thework isjustified
because itisthedisease thathassuchenormous proportions thatasmall contribution hasanenormous
impact. IntheUnited States andCanada, toputitintoperspective foryou,thereisanewcasediagnosed
approximately every 29minutes. Soyoudon'tneedtomake abigdenttohaveahugeimpact. Ithink
thework isentirely justified, butforthose whoarelooking forquick fixes, it'sgoing toberelatively
unrewarding. Theanswer isn'taround thecorner.
Chairman
647. It'saround 4o'clock. Howlongareyouplanning toproceed orshallwemake aninception
withtheCommunity presentation. What would yousuggest?
Mr.Thompson (Canada)
648. Mr.Chairman, notwithstanding theslowstart, ifyou'llpermit me,I'lltake30seconds tothank
thescientists fortheirveryhelpful andconcise answers andturnthephone overtoMr.Christoforou
by4o'clock, ashewished.
Chairman
649. Thank youverymuch foryourunderstanding.
650. MayIgivethefloor totheEuropean Communities, Mr.Christoforou.
Mr.Christoforou (EC)
651. Iwould liketothank theDelegate ofCanada forhisunderstanding, inthisparticular case.WT/DS48/R/CAN
Page360
652. Before proceeding, Iwould liketoremind youthatwehaveformally requested through the
Panel, Dr.Ritter, thepaper ofDr.Truhaut andwewould appreciate ifwecanreceive acopyofthis
paper forourscientists tohavealookatthis.
653. Thespeaker whowillbeleaving veryshortly isDr.Adolfo Pérez-Comas fromPuerto Rico,
whohasbeen investigating thepossibility ortheexplanation ofawide-scale premature sexual
development inPuerto Ricoformore thanabout 20-25 years.
654. Iunderstood there were some problems raised bytheDelegate ofCanada whether these
projections willbemade. Icanonlyannounce there are,Ithink, 11or12slides. Some ofthem are
graphs showing theincrease ordecrease according towhich dietisfollowed, andtheyareonlyslides
which show whatexactly wearetalking about. Ihaveviewed myself these slides andwhattheyare.
Most ofthem aredocuments andcharts ofestimations andthere areonlytwoslides withtheeffects
onchildren, pre-pubertal girls, whatitisabout.
655. Iwould givethefloorifourcolleague fromCanada orprobably theUnited States, would like
tomake acomment.
Chairman
656. Mr.Brinza.
Mr.Brinza (US)
657. Asmycolleague fromCanada hadindicated earlier, weshare similar concerns withtheproposed
presentation. Itsounded from thedescription Ijustheard, thatwearetalking about apresentation
ofnewscientific evidence, notapresentation designed tofallwithin thepurpose ofthismeeting, today,
which istotalkabout theresponses tothe28questions ofthefiveexperts, andtherefore wedon't
seehowthisisappropriate, atthispoint intime.
Chairman
658. It'shardtotalkabout something youdon'tknow. Thequestion iswhether thiscomes inas
newevidence orwhether itsupports whathasbeensubmitted bythedate. Asapractical matter, this
material canbeintroduced tomorrow, atanyrate.Youcould dothisinthesecond substantive meeting.
Andfrom thatperspective, justaverypragmatic point ofview, Ithink it'ssimpler ifit'sdonehere.
Mr.Thompson (Canada)
659. Areyousaying it'spossible tointroduce evidence ofthesecond oralmeeting tomorrow?
Chairman
660. I'mafraid Ierred. Lawyers areoften known asbeing champions forprocedures. Butthe
verygood lawyers areinterested inthetruthandsosometimes theysubject procedures tothefinding
ofthetruth, butthisdoesnotalterthefactthat,yes,wecannotintroduce newevidence.
661. Whether it'sdonetoday ortomorrow. Itwould really depend onwhether it'swithin therealm
ofwhathasbeensubmitted by8February.
Mr.Christoforou (EC)
662. TheUnited States hascirculated previously adocument which wasnotsubmitted bythe
8February. Theissue about theincidence inPuerto Rico hasbeen argued bytheEuropeanWT/DS48/R/CAN
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Communities, bothinthesubmissions concerning theUnited States extensively, andinthefirstand
second submission forCanada.
663. Theissue hasbeentouched. Itwaswithin thetime-limits. Itisnotnewevidence. Itisan
elaboration ofwhatisalready inthesubmissions.
664. Icould nothavetheslides soIcould sendthem before the7th. Thatiswhat so-called the
newevidence, theslides, butIhaveherealsothedocuments which Iwould request theircirculation.
Ifyoudon'tallow theslides, sowecancirculate thedocuments andhavealookatthem, butyouwill
missthe"nice" pictures ofgirlsunder theageof8withexactly whatwearetalking about. Thisis
notanewdocument. They arewellaware oftheissue. Wehavedebated thisduring thesecond
substantive meeting. TheUnited States hassubmitted documents about thiscase. Theyarealsoannexed
heresowedon'treally takejustoneview. Thedocuments submitted bytheUnited States, areinthis
document. Icancirculate thedocument ifyouwishandtheslides arethere. There 'snonewevidence
inthiscase.
665. Bothofthedelegations were aware when wediscussed forthefirsttimeon7January.
Chairman
666. Yes,Mr.Thompson.
Mr.Thompson (Canada)
667. IfIcould respond, Iamnot,noristheCanadian Delegation afraid ofthetruth. Butasan
experienced lawyer Iknow that,justasinscience, there areagreat many truths. Andwhat Iam
concerned about, Mr.Christoforou hasraised what occurred on7January. Youwillrecall thatI
specifically asked Mr.Christoforou toidentify theexperts heproposed tocallsothatwewould have
anopportunity ofpreparing ourselves todealwithwhatever evidence theyhadtopresent. Hehas
never, untilyesterday, indicated thatthisevidence wasgoing tobecalled orwhothisperson was.
668. Asamatter ofsubstantive fairness, irrespective ofprocedure, itisunfair topermit someone
topresent onesideofanissuethatmaybecontroversial andinflammatory without aproper opportunity
ofhaving evidence thatmaygotoanother point ofview.
Chairman
669. Mr.Brinza.
Mr.Brinza (US)
670. Iwould alsopoint outthatwhether theyareslides ordocuments, ifthepoint istogoback
toissues orpoints thatwere raised inprevious submissions andmaking another presentation here,
thatisnotthepurpose oftoday'smeeting. Thatwould make thisanother substantive Panel meeting.
Thatisnotwhatweareherefor.TheCommunity hadplenty ofopportunities inourPanel process
topresent thisandtheysaidthattheyalready have. There isnoreason togothrough thisagain today.
Wearenottalking about being afraid ofthetruth, butaslawyers, those procedures, Iliketothink
aredesigned tohelptomake surethatthetruthisbrought outandhaving breaches inthose procedures
isnotawaytoensure afairness andafairairing ofthefacts.
Chairman
671. Mr.Christoforou.WT/DS48/R/CAN
Page362
Mr.Christoforou (EC)
672. Mr.Chairman, from what Iheard, theybothdon'tdeny thattheissue oftheincidence in
Puerto Ricohasbeendiscussed extensively inthesubmissions. Thisistrue. IseeQuestion No.7
ofthePanel totheExperts saying isthere anyevidence andscientific evidence available which
demonstrates thatthepotential foradverse effects onhuman health arise andwhether there isany
evidence tothateffect.
673. Aswedidyesterday, Icould haveDr.Pérez explain orally, astheother scientists did,since
theissue hasalready beentouched before. Ifyouindeed insist thatthese slides arenotprojected, at
least, there isaquestion totheexperts andweareallowed tomake comments.
674. Aswedidyesterday, wecanelaborate fiveminutes andthenanswer thequestion. Isthatreally
outside whatistheunderstanding oftoday'smeeting? Youhavebeencirculating documents yesterday
andwecancirculate those documents, aswell. There isaspecific question ofthePanel onthisissue.
Soasweagreed yesterday, hemaymake thispresentation tenminutes orally andhavenoprojections.
675. Mr.Chairman, Iwould forcefully really object tothattypeofprocedure which isapplied only
unilaterally, inthiscase, I'mafraid. These issues andfactsshould beexplained inthepresentations
andthere isaquestion which wewould liketocomment onandprovide areply andaskaquestion.
Chairman
676. AsIsaid,itisdifficult totalkabout something youhaven 'tseen, sologically wehavetosee
itbefore wecanmake aruling. ButIdon'twanttospend toomuch timeonthese procedural questions
andIwould invite youtomake thepresentation. Thentheparties would haveanopportunity tocomment
onthis,iftheywantto,theUnited States andCanada. Sothefairness ispreserved.
677. ThePanel would perhaps reserve it'srighttosubmit oneortheother question totheexperts.
SomayIaskyoutogoahead withthepresentation?
Mr.Christoforou (EC)
678. What should Iunderstand bypresentation. Should Imake itmyself?
Chairman
679. No,no.Your expert, please.
Dr.Adolfo Pérez-Comas (EC)
680. Thank youMr.Chairman. Good afternoon ladies andgentlemen, members ofthePanel.
681. Myname isAdolfo Pérez-Comas. Iamapediatric endocrinologist andclinical geneticist,
fullytrained under United States 'standards andcertified inendocrinology andmedical genetics under
United States 'standards andanadvisor totheCentre forDisease Control andtheNational Institute
ofHealth intheUnited States intheareaofmyspecialty, participating atdifferent ongoing steering
committees, bothattheCDC andNIH. Iamalsoanassociate professor ofpediatrics atthePonce
Medical School andpreviously attheMayaguez Medical Centre andtheUniversity ofPuerto Rico
Medical Science campus.
682. Wearegoing topresent toyoutoday accurately documented datacollected inPuerto Rico
thathasbeenpublished inprime medical journals, suchastheLancet, theNewEngland Journal of
Medicine, theJournal ofPediatrics andtheAmerican Journal oftheDiseases ofChildren, aswellasWT/DS48/R/CAN
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inthePuerto Rican Medical Association Medical Bulletin thatisacertified journal inindex medicals,
andallofthese journals arepeer-reviewed byleading scientists inthefield, intheUnited States and
intheworld.
683. Iwillcondense herethe50-year history ofPuerto Rican exposure tohormones with28years
inthepractice ofpediatric endocrinology with14slides presenting anomalous sexual development
inmycountry.
684. Imight alsoaddthatPuerto Rico isthesecond-largest producer, atthemoment, oforal
contraceptives andhasbeenexposed forover40years tooralanti-conceptives because theyweretested
inPuerto Ricoprior toitscommercial disposition intheworld.
685. Original studies were carried outintheisland ofPuerto Ricointhelate50s.
686. Theaspect considered today hasbeenpresented atguest lectures intheUnited States, Canada,
Spain, Cuba, Venezuela andtheDominican Republic. Thisisasummary ofthepatients wehaveseen
under ourcare,dating backto1969, uptotheyear1985 andpartof1986, where mostofthestudies
carried outbytheCDC weredoneatthesame time. Wearenotincluding recent data. Wearejust
going backtothedatewhen thedatacollected bytheCDC wastaken on.
687. Thisisayear-and-a-halfoldfemalechildthatpresentsanomaloussexualdevelopment,categorized
aspremature telarche, because shehasisolated breast development, thatisnotnormal forachildeighteen
months old.Breast development should appear normally inourpopulation aftereight years ofage.
Ifyouhavepubic hairorlaxial hair,thatshould notappear before theageofnineyears, andifyou
havepremature menses ormenarche, itshould notbepresent inanybody before tenyears ofage.
Anyone ofthose conditions thatappear before those ages, isnotnormal. Itmaybesecondary tothese
differentprocessesortumoursintheorganismoritmaybesecondarytoexogenoushormonesindifferent
areas thatcanbepresent.
688. Thisisaten-year oldgirlwhopresented breast tissue atseven years, whopresented pubic
hairatanormal age,attenyears, whopresented menarche atanormal ageoftenyears, butwhoalso
presentedpolycysticovaries,ahighlyelevatedserumtotaloestrogenforherageandextremelydeveloped
breasts, thatIclassify asvirginal hyperphacial ofthebreast, acondition thatwasnotpreviously
associated withpremature telarche orwithincreased serum totaloestrogen.
689. Thisisanother aspect oftheproblem weareseeing inPuerto Rico. Wehavesevere cases
andwehavemildcases anditaffects children ofanyageanditaffects males, itaffects females and
itdoesn'taffectonlyPuertoRicans.Itaffectscontinentals,NorthAmericanslivingintheisland,German
people living intheisland, people fromLatin America living intheisland. Once theygetthere, some
ofthem suffer from these problems.
690. Inthepatients wehavestudied uptothatdate,wemeasured, inasignificant number ofthem,
thelevelofoestrogen. Andwemeasured specifically thatserum totaloestrogen thatwerecarried on
under thesame standards ofDr.Arnold presented yesterday, inthetable withthenormal value as
specified andthisprocedure wascarried onindifferent United States 'research andcommercial
laboratories, Biosign, Intersign, Project Clinical Laboratory inmainland United States andnotinPuerto
Rico.
691. Approximately 85percentofthose malepatients whoweretested and86percentofthefemales
thatweretested, presented highoestrogen levels. Iamspeaking of522patients hereandIamspeaking
hereof146males withahighoestrogen level. Iamnotspeaking of30patients, ofninepatients or
of15patients. These areasignificant number ofpatients whopresented highoestrogen levels.WT/DS48/R/CAN
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692. When westarted studying these clinical cases intheearly 70swefound anincreased sizeof
theuteri. Atthatmoment wedidn'thaveavailable sonographic studies, laparoptomies insome children
wehavetoinvestigate whathappened intheovaries. Theuterus wasfound enlarged insome ofthem
withthepresent ovarian cysts. When westarted having available pelvic sonogram, thisstudy was
alsodoneinasignificant number ofpatients whocanafford topayforit.Outof447pelvic sonogram
studies, infemales withanomalous sexual development, 276ofthem presented abnormal pelvic
sonograms, enlarged uteri, polycystic ovaries, thesamethatcanbeseeninoestrus, inanimal husbandry.
693. 62percentofthose girlspresented ovarian stimulation syndrome. When westudied thebone
cage, wefound thatin26percentofourpatients, theboneagewasaccelerated. Thisimplicates that
theexcess ofhormones thatwaspresent inthesechildren havebeenofmoreprolonged duration because
itwasaccelerating theboneageofourchildren. Thisdatahasbeenpublished intheNewEngland
Journal ofMedicine, hasbeenpublished inthejournals Ihavementioned previously, andcanbe
corroborated byanyone.
694. Weweresearching forthepossible cause ofthisinourisland. Welooked forexogenous causes
because thecondition didn'tfitwhatitshould beinanormal endocrine situation.
695. Asapediatric endocrinologist, Ishould seeone,twoorthree patients withabnormal sexual
development inayear. Once uponatimeIwasseeing fourorfiveaweek andsome daysIwasseeing
three orfour, inthesame day,newcases.
696. Wefound in1982 thatthediethylstilboestrol wasbeing soldoverthecounter inPuerto Rico,
thiswasdoneinonelocalagricultural store inPuerto Rico. ThatRalgro orZeranol wasalsobeing
soldoverthecounter atthattime. DESwasbanned intheUnited States atthattimeandPuerto Rico
hasthesame rules andregulations astheUnited States, andduetothat,westarted suspecting that
something wasinthefeeding ourchildren were getting andwestarted agroup ofourpatients ona
diet. Wemodified thedietwithlimited ingestion ofmeat, poultry, milkandeggs. Inaperiod offour
tosixmonths, themales thatwere onadiet,60outof103,58percentofthem presented apartial
remission ofthecondition. Theabnormal hormones intheblood started going down, thebreast tissue
thatwaspresent started todiminish, those thathadpubic hairshowed nodifference, itdidnotincrease,
butitdidn'tdisappear.
697. Inthefemales, weobserved more atthesame period oftime, 51percentreduction withthe
dietandapartial remission andevenatotalremission ofthesymptoms wehaveobserved before.
AsIpointed outpreviously theyhavebeenpublished bythatdate. 11percentofthefemales and
sixpercentofthemales onnodiet,alsohadaremission, buttheremission presented inayearand
ahalftotwoyears. Inanobvious period during which thedietmayhavechanged byitselfingrowing
children. Thisconfirmed indirectly thatweweredealing withsome kindofexogenous contamination.
There were notcases oftrueprecocious puberty byendogenous origin.
698. Thisremission ispresented hereregarding thedifferent agesin1969, 1970, 1972, 1973. There
wasverysmall remission because wehadnotintroduced thediet. When weintroduced thediet
modifications andafterthere wasabigpublic awareness intheisland when thissituation appeared
inonepatientintheTimemagazineoftheUnitedStates,theremissionstartedincreasing.Noteverybody
remitted butasignificant number ofthem didsowiththemodification indiet.
699. TheFDAdidsome screening studies andthisisacopyofoneofthose studies, where apoultry
fromBonito Puerto Ricoandapoultry fromRoyal Brothers Processing inMississippi werefound in
thisscreening study aspositive foroestrogenic substances. Posteriorly ithadbeenreported thatthese
were negative inthenextstudies thatwere performed bytheFederal agencies.
700. Dr.Carmen Saenz whohasbeenworking inthisareawithme,whoatthesametimepresented
apublication inthesame bulletin ofLancet asIdid,Ipresented a272pageandhepresented 350ofWT/DS48/R/CAN
Page365
thesame condition. Shemeasured percentage ofzeranol through alaboratory inParis byDr.Morfine
where fiveoutofsixpatients thatweresotested revealed levels ofwhatappeared tobezeranol, by
thattimeorazeranol-like substance, confirming indirectly thesuspect wehad.
701. Wehavenowascreening testpositive foroestrogens andatest,possibly positive, forzeranol.
702. In1986, Dr.FredE.Titulowel(?), another collaborator from theCDC, published anarticle
onanepidemiological study doneinourpatients inPuerto Rico. 50ofmypatients, 60ofthepatients
ofDr.Saenz andapproximately 20more patients from theUniversity Pediatric hospital inSt.Juan.
703. Initially, weweretoldthatthisstudy didn'treveal anyrelation towhatwewereseeing related
toexogenous hormones, butifyoulookindetail intheconclusions ofthisstudy, thisstudy reflects
apositive andstatistical association between premature telarche andtheconsumption ofsoya-based
formula, which hasbeenwidely known foralongtime, various meatproducts andamaternal history
ofovarian cysts.
704. Obviously themother iseating thesame foodasthechild andthefamily. With theclinical
experience wehavewiththedietandwiththepresumption ofthelaboratory study, wemustconclude
thatwearestrongly thinking thatanexogenous thing ishappening inPuerto Ricoandisstrongly
suggestive ofanexogenous contamination bythese substances.
705. Lastweek, on2February, thegovernor ofPuerto Ricounder theprogramme oftelarche, that
istheonlyonethatexists intheworld made some declaration totheSanJuanStar,thatisthelocal
press. Thenumber ofchildren withsigns ofearly sexual development nearly doubled inthepastsix
years according tofigures released byasurvey byoneoftheisland 'stopexperts onthiscondition.
Thestatistics addsfueltoconjecture thatPuerto Ricohasthehighest incidence ofpremature sexual
development intheworld. There isnoother place intheworld with asimilar situation said
Carlos Bourdony whorunstheHealth Department 'sPremature Telarche andSexual Development
Programme.
706. Astudy tobepublished intheApril issue ofPediatrics, theOfficial Journal oftheAmerican
Association ofPediatrics suggests thatgirlsseeninpediatric office practice aredeveloping pubertal
characteristics atyounger ages thansuggested instandard pediatric textbooks andbyearlier
United States 'studies. Early sexual development hasbeenmonitored inPuerto Ricosince 1988when
thelocal health department setuparegister, theonlyoneofthiskindintheworld, according to
Dr.Bourdony. Todate, 6,115 cases ofchildren withpremature sexual development have been
documented bythePuerto Rican Department ofHealth.
Chairman
707. Could Iaskyoutocome toaclose. Youhaveonemore minute.
Dr.Adolfo Pérez-Comas (EC)
708. Thisfigure isnearly double. The3,162 cases documented between 1969 and1991 anddo
notinclude the4,500 patients evaluated byDr.Saenz andmyself. Thisincludes thepatients evaluated
bytheother 11endocrinologists. [Tape ends]
...studies .....performed bytheUSDA Department ofAgriculture found nosignificant ortracelevel
ofgrowth andenhancing hormone inthelivestock specimen, according toBourdony. Butintheabsence
ofconclusive research, wecan'tsaythisfactor hasbeen completely eliminated, asisstated by
Dr.Carlos Bourdony, theHead ofthisTelarche Programme oftheDepartment ofHealth inPuerto
Rico. Thank youverymuch, Mr.Chairman.WT/DS48/R/CAN
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Chairman
709. Thank youverymuch Professor foryourveryinteresting presentation. Thematter wasraised,
reference wasmade inearlier proceedings totheCosta Ricastudies. Wewillassess towhatextent
newevidence wassubmitted here, inparticular, IrefertoanApril study which seems tobenewto
usandthePanel willreserve itsrights toregard ordisregard theevidence submitted inthelightof
thistesthere. Iwould nevertheless asIindicated briefly, givetheopportunities toCanada andthe
United States tocomment onthis. AndIcansummarize ofcourse myimpression thatnothing has
beensaidabout therealcauses which mayhaveledthissituation anditwould takeveryelaborate
discussions togointothishere.
Mr.Thompson (Canada)
710. Thank youMr.Chairman. Thatwould bemyimmediate reaction aswell, asIamunsure how
anyofthismaterial relates totheissues thatthePanel mustdecide. IfIwastobeputting questions,
Iwould beinterested toknow whattestsmethodology wasusedforzeranol, weretheresults confirmed,
andwhatismeant byazeranol-like substance?
Chairman
711. Thank youverymuch, Mr.Brinza.
Mr.Brinza (US)
712. Thank you,Mr.Chairman, onemoment please. Iwould liketohavesome ofourexperts
comment onthisverybriefly. Dr.Miller whoisherewithusisfamiliar withthissituation, asare
some ofourother experts aswell.
Chairman
713. Thank youverymuch.
Dr.Margaret Miller (US)
714. IamDr.Margaret Miller, Centre forVeterinary Medicine, FDA, andIwould liketosaythat
these types ofhealth effects areverydisturbing totheAgency andweexpended alarge amount of
research dollars andenergy, asdidourcolleagues attheUSDA, investigating thissituation. Andas
aresult ofthatactivity weconcluded thatthissituation isnotduetothehormones present inmeat
from animals treated withapproved products usedforgrowth promotion.
Mr.Brinza (US)
715. AndthisisDr.Richard Elliswhoisalsofamiliar withthissituation.
Dr.Richard Ellis(US)
716. Thank you,Mr.Chairman. Ihadaresponsibility forcoordinating oursampling programme
during thatspecial study. Infactweactually conducted three studies, overtheperiods ofwhich were
referenced bythispresentation. Thethirdstudy which weconducted wasbyfarthemostextensive
oneandwelooked atapproximately 700samples thatwerecollected from beefanimals, piganimals
andpoultry. Welooked atbothdomestic production from slaughter plants, from imported product
atinspection sites, andalsoproduct collected atlocalmarkets. AndasDr.Miller said,inallofour
studies, wedidnotfindthepresence ofanyzeranol, DESorrelated products inourstudy. Butin
asmuch aswedidnothavemethodologies foralltheproducts thatwewould havelikedtohavelookedWT/DS48/R/CAN
Page367
at,weevensubmitted aportion ofthose samples forbioassays byFDA. Andwehadnegative results
onthose bioassays ofsamples submitted toFDA forthatpurpose. Ifitwould beworthwhile tothe
Chairman, when wegobacktoWashington Iwould begladtosendyoucopies ofthose documents
tosupport mystatements. Thank youMr.Chairman.
Chairman
717. Thank youverymuch. MayIaskwhether oneofthemembers oftheexperts would liketo
takethefloor onthispresentation here? Yes,Professor McLean.
Dr.McLean
718. Ijustwould liketomake twocomments. Firstofall,Ireally donotseewhatthishastodo
withtheissueofusing hormonal growth promoters inaccordance withgoodanimal husbandry practice.
Andjustacomment, theuseoftheword "zeranol-like" would suggest tomethatthere iswidespread
contamination offoodmaterial withFusarium fungi, fortheFusarium fungus which produces zeranol
anditsrelated compounds, sothatmight givesome indication astowhat onemight lookforifone
islooking atacontaminant. AndIwould drawattention tothePanel thatzeranol wasactually discovered
because Fusarium contamination ofpigfeed, asIremember it,produced signs ofoestrogen responses
inpigs, asIremember it.Itwasfrom there thattheresearch work identified thatitwasaproduct
offungal metabolism bytheFusarium species andonitwent there. SoIwould suggest thatthe
Puerto Ricans might liketoinvest some money onwidespread looking ofwhere theFusarium is,what
species itisandwhatitisproducing. ButIdonotbelieve thatthishasanyrelevance totoday'shearing.
Dr.Lucier
719. Excuse me,ifIcould addabittothat. Itisknown thatzeralenone andzeranol-like substances
produced fromFusarium doproduce hyper-oestrogenism inswine andincattle, which itfedmouldy
cornthatcontains highlevels ofthis,andlikewise itcancause neonatal problems, buttheseareusually
massive amounts. ButthenIthink therehavebeensome Indian tribes intheUSwhohaveeaten large
amounts ofmouldy corninwhich therewasoestrogenic responses which areadverse aswell. Sothere
isinformation intheliterature astosuggest thathighlevels ofthese, cancause adverse effects, ina
number ofdifferent ways. Theamounts thatarepresent ingrowth promoted animals, however, have
beenvery, verymuch lower thanthisandwould notproduce those kinds ofchanges thattheywere
reported here.Although itispossible zeralenone substances frommouldy cornandotherproducts could
doit.
Chairman
720. Thank youverymuch. Canweclose thediscussion onthispresentation. Mr.Christoforou?
Mr.Christoforou (EC)
721. Mr.Chairman, ifyouwillallow uswewould suggest thatthispresentation isabout 90per
centareproduction ofthedocument thattheUnited States hascirculated during thesecond oralmeeting
wehadhereon11November. Asrightly Dr.Pérez hassaid,there aresome uncertainties about the
actual cause, buthehasprovided someinsights, someinformation onthepotential possible explanations.
Inthearticle which theUnited States hasamended totheirsubmission during thesecond meeting of
thePanel, thatwastheofficial explanation given bytheUnited States andwhat wedidisthat
Dr.Stephany hasgonetoday through thearticle provided bytheUnited States asanexplanation of
thesituation inPuerto Rico. Hewould liketomake atwo-minute statement about theanalytical methods
used, inthatarticle provided bytheUnited States inthiscase.WT/DS48/R/CAN
Page368
Chairman
722. Isitabsolutely necessary? Because westillhavealisthereofquestions which areverymuch
tothepoint hereandwedonotwantto,butIdoappeal toyouandurgeyoutoselfrestraint justto
really submit issues which arepertinent. Thank you.
Dr.Stephany (EC)
723. Thank youMr.Chairman. Some material hasbeendisclosed tomeyesterday andtonight.
Iamnotquite surewhether thatisthedocument Dr.Christoforou spoke about, sohaveItomake
thatrestriction, butbasically itisnotessential. Ihadthepleasure in1983according tomyrecollection,
thatDr.Alice came tomylaboratory andwediscussed thewhole case. Atthattimewehadsuperior
technologies available forhandling these problems, unfortunately samples never showed upandfor
methecasewasclosed andonlyyesterday Isawsome details. Iwillnotgointoanydetails but
summarizing whatIhaveseen,Iwasverymuch surprised about thesmall amount ofpotential substances
thathavebeenchecked orcould beseenbythetechniques usedatthattime. Thatwhat especially
inthefieldofthezeranol-like compounds, Idonotthink thatIhaveanycriticism basically, butsome
oftheso-called bioassays andreceptor-assays Ithink Ihavesevere criticism thatpotentially strong
oestrogens haveslipped through thesystem, notbeing detected. Sostating itveryshortly thatnothing
hasbeenseensoitcould notcome from xenobiotic oestrogens, maybe thatisalittlebittoostrong.
ButDr.Miller summarized thatthisdidnotcome fromthecompounds thatareintheregular implants
orthose implants thatoncehavebeenregular, likediethylstilboestrol. SoIdon'twanttogointoany
details, Ionlyofferonceagain afterallthose years tocooperate, toclarify thisveryintriguing affair
inPuerto Rico. Butwhatever thecause is,itisaveryserious problem, andIlearned frommycolleague
thattheproblem hasnotstopped, elsewhere intheworld alsosimilar problems areshowing up.That
iswhatIhavetosay.
Chairman
724. Thank youverymuch. Mr.Christoforou youmaycontinue.
Mr.Christoforou (EC)
725. Thank youMr.Chairman andthank youverymuch indeed. BoththeUSandtheCanadian
delegation ofthisparticular issue, which wasofserious concern totheCommunity because wehave
beenmaking thisargument since theverybeginning. With yourpermission then, ournextscientist
whowillbeleaving isDr.Adlercreutz. Hehasalready provided thepaper within thetime-limits.
Forthispaper theUnited States havealready made comments andIwould statethatDr.Adlercreutz
willtouch onlyupon onewhich wethink important andrelevant issue inthiscase. Iwillgivethe
floor toDr.Adlercreutz.
Dr.Adlercreutz (EC)
726. Iwasasked tosaysomething about thepossibility ofcarrying overanabolic steroids tohumans
aftereating meat. Ihavebrought withmeoneofthearticles, andtheother because Icame yesterday
fromtheUSA, Icould notrecover thesecond one. Butinessence itissothatwecannever besure
thatthefarmers really usethesubstances theyarelegally asked touse. Inthisarticle written by
Demetrios Esgotas andTomTuten fromtheDepartment ofPathology andLaboratory Medicine Emory
University School ofMedicine inAtlanta. Noexcuse me. ItwasDebruyckere, Sagher and
VanPeteghem andthisisfromtheNetherlands, inGhent, Belgium, excuse meyes[passage unclear].
Ireceived thisyesterday. Inanycasetheystatehere, inthiscountry Iknow thattheyareverycareful
withtheirtesting ofthemeatandtheytested in1990-1991 608injection sites. Andtheyfound that
over60percentcontain atleastoneillegal anabolic agent. AndIhaveaverylongexperience intheWT/DS48/R/CAN
Page369
doping fieldandIwould saythatIamoftheopinion thatitisimpossible thatgoodveterinary practice
isusedbecause there issome bigeconomical benefits ofgetting ahighgross. SoIwould liketoask
theAmerican delegates andCanadians also,whether anysuchstudy hasbeendoneintheUnited States,
testing really howmuch illegal anabolic steroids areused. Infactthere aretwoarticles, onewhich
Icouldn 'tyetgetbutIwaspresent atthemeeting when itwaspresented, andtheyfound inpeople
whowerenotsportsmen andnottaking partinanysuchactivities which would needanabolic steroids,
theyhadfound onecasewithnandrolone metabolized inurine which musthavecome fromthefood,
because there wasnoother possibilities. Andthentheydidthisstudy hereandfound inthecontrol
group onesubject whohadclostebol which isanabolic steroid intheurine, despite thatthere wasno
possibility thatthisperson hadtaken anydrugs. Then theyadded alittlebitofthisdrugtomeatand
fedittosome people andfound thattheycould detect bydoping teststhesecompounds. Andweknow
from thedoping fieldthatforexample, nandrolone injected intohumans canbedetected fourtosix
months aftertheyhavebeengiven. So,inmyopinion itisaveryserious thing ifsportsmen arecaught
andgetting doping positive samples, iftheyeatmeat. Andtheriskaswellisrelatively high, because
nowitisnecessary forevery doping laboratory tohavehighresolution apparatus, soitmight bethat
theycandetect evenaftersixmonths, soverysmall residues inmeat. Imean I'msurethatifyou
testthings inmeatandyougetnegative results youcanstillfindthese compounds inurine, absolutely
sure,becausetheurinemethodsareextremelysensitiveandthemeatmethodsarenotsosensitivebecause
itisdifficult toextract thesecompounds. SoIwould liketoaskwhether thisistaken intoconsideration,
thatthefarmers don'tfollow therules andthatthisisinfactverycomparable tothesports field?
Chairman
727. Thank youverymuch. According toourrulesthesequestions maybesubmitted totheMembers
ofthePanel andmayIinvite youtocomment onwhatDr.Adlercreutz. saidandIalsorefertothe
paper which wascirculated, theevaluation ofthe32nd report ofJointFAO/WHO Expert Committee
inFood Additives andthediscussion ofProfessors Liehr'sreport. Have youbeenabletoreadthis?
Butifnot,could youcomment onthethesis thatDr.Adlercreutz issubmitting.
Dr.McLean
728. Pigsandhorses naturally produce 19nortestosterone andwefindthatderivative oftestosterone
intheirtissues andinurine. They canalso,using thesame enzymic pathway, produce 19norsteroid
derivatives ofanabolic steroids, which ispermitted innormal therapy inhorses forcertain disorders.
Andsoitmaywellbepossible thatthehuman athletes haveeaten pigorhorse meatwhich could be
thesource of19nortestosterone, orevenmayhaveeaten horse meat from horses which havebeen
treated 19norsteroids. Andsotherefore itdoesnotsurprise methesortsofresults thatDr.Adlercreutz
hasreported areso.
Dr.Arnold
729. Itseems toconfirm whatIhavesaidyesterday andtoday andwhatIhavealsosaidinmywritten
answers. There isasignificant black market inEurope andinsome countries itismore important
thaninothers. SoIperfectly know that,specifically inBelgium, alonglistofillegal substances are
regularly found. Theauthorities spend alotoftimeandmoney toanalyze many samples. ButIdo
notseewhattherelevance iseither thelegaluseforgrowth promotion orfortherapeutic purposes.
Imean, onbothsides oftheocean, wehavestrict rules andweseeanexample thatononesideof
theocean these rules areviolated.
Dr.Randell (Codex)
730. The1984 FAO/WHO expert consultation certainly pointed outtheopinion oftheexperts at
thattimethattheillegal useofveterinary drugs created afargreater potential public health problem
thantheregulated useforgrowth promotion. Ithink thatthatfinding in1984 probably stillstands.WT/DS48/R/CAN
Page370
Iwould liketopoint outtwotextsadopted bytheCodex Alimentarius Commission, andImight add
adopted onthebasis ofconsensus, bytheCodex Alimentarius Commission. Therecommended
International Code ofPractice fortheControl anduseofVeterinary Drugs andtheCodex Guidelines
fortheEstablishment ofaRegulatory Programme fortheControl ofVeterinary Drug Residues inFood.
Both ofthese texts exist toguide governments inestablishing control practices andincontrolling
veterinary drugresidues. Togodeeply intothesecond oneofthose texts, itdoesgetintoalotof
sampling statistics andunfortunately sampling statistics tendtoshow thatunless youarewilling to
essentially sendallofyourfoodsupply tothetestlaboratory, andtherefore starve todeath, youare
notreally going tofindwhatitisyouwanttofindatvery, verylowlevels. Sosporadic cases such
aswehaveheard could probably exist evenwithin theframework ofaproperly regulated control
programme.
Mr.Christoforou (EC)
731. Before Igivetheflooragain toDr.Adlercreutz Iwould liketosaysomething, something which
probably might haveescaped thepoint which wewere trying tomake. Thepoint wearetrying to
make isnotonlyfrom illegal use,itisalsoaswehaveheard yesterday from Dr.Lucier, thatthere
isaprobability evenfrom theuseaccording tothegood agricultural veterinary practice. Itmaybe
anincrease atwhatwecould call,butwedonotknow whatexactly itisthenormal physiological levels.
Iftheyareallowed tobeused, asitisintheUnited States andCanada, there isapossibility theymay
be,more possibility thatthese increases maybefound. Andthepoint Dr.Adlercreutz wastrying to
make isitmayhaverepercussions notonlyontrade issues, these questions, butmayaffect legitimate
sports activities because suddenly people bysimply eating meatmaybediscovered tohaveincreased
quantities ofthose residues which theywilldisqualify themfromthegames without themhaving done
anything wrong. Thatisthepoint Dr.Adlercreutz wastrying tomake.
Dr.Adlercreutz (EC)
732. Thisisinfactoneofthepoints. Intheother paper, Iamwellaware that19norsteroid
metabolites occur incertain animals andsoitwould bepossible naturally andtheoretically thatthese
people havebeeneating, Idonotthink horse meatashorse meatisnoteaten much inEurope, itmay
bepigmeat. Butinfactthere hasnotbeenshown thateating thiskindofmeat youcangetthese
metabolites inhuman urine. Buthereinthispaper infacttheclostebol isnotfound inanyanimal
andheretheyfound onecasewithclostebol inthecontrol group sothere isverylittlechance thatit
came fromanyother source thanthediet. ButwhatIwould alsoliketopoint outisthatwhich Ialso
pointed outinmyreport, isthatweknow verylittleabout theeffects ofthissteroid inthebrain. And
Ihavepersonal experience alsowithregard tothebehaviour ofathletes bothbefore andaftertaking
anabolic steroids. Andweknow nowbecause thisneuro steroids inthebrain occur inveryverylow
concentrations andyouneedverysmall things tochange thelevels ofnormal steroids inthebrain.
They arereally atverylowlevels active. Soifyouthink thatyouconsume meatcontaining lowlevels
ofanabolic steroids every day,theywillbetransferred viatheblood brain barrier andtheoretically
could interfere inthebrain. AndIhavebeeninvolved inpolice cases andinsevere depression cases
aftertaking anabolic steroids andnaturally thedoses havebeenhigh. Butnowknowing thework by
Etienne Emile Beaulieu inFrance which shows thatthese areverylowamounts which areneeded to
change, forexample, animpression ofanimal ofanother animal, canchange theirlevels verylittle,
butsignificantly. Soitispossible thatlowlevels ofsynthetic steroids canaffect ourbrain longterm
andverylittleisknown about thatandIhavenotbeenabletofindanystudies showing howhighthe
concentrations of,forexample, anabolic steroids, areinthebrain afterintake. Idonothaveanysuch
material, butIamalittlebitreluctant because ofthisphysiological observations made recently inrecent
years.WT/DS48/R/CAN
Page371
Chairman
733. Mr.Christoforou, howlongwould youintend togo?Wewanttoreserve some timeforfinal
questions bythePanel which areimportant tous.
Mr.Christoforou (EC)
734. Mr.Chairman, Ithinkitmaytakemeprobably untilquarter tosix.Itwilldepend onthereplies
Iwillbegetting from thequestions ofcourse, butabout quarter tosixorsixo'clock, butIhavea
number ofquestions andIwillcutalotofthem, butitwilltakemereally some time.
Chairman
735. Ihaveafeeling thatabreak would dogoodtothismeeting. Wewould resume, ifyouagree,
inquarter ofanhour, buttrytocutitdown totheessentials. Thank you.
Chairman
736. Iwould liketogivethefloor totheEuropean Community forcontinued intervention.
Mr.Christoforou (EC)
737. Mr.Chairman, yesterday weleftthediscussion atthepointwhere wewerediscussing theissue
whyJECFA hasnotfixed anacceptable daily intake forthethree natural hormones. Andthere was
anargument going between, asIunderstood, Dr.Lucier andDr.McLean, whether thatwasfirstof
allfeasible tobedoneandthenifitwasfeasible, whyitwasnotdoneinthatcase. Thisisalready
withtherecord ofthePanel atthispoint, butIwould liketorecall andthencome backwiththeprecise
question.
738. Wehave already explained inoursecond written submission tothePanel thatthe
European Community doesapply maximum residue limits andtests, asIsaidyesterday, 59,000 in
serum forthethreenatural hormones. They arethevalues given hereonpage16ofoursecond written
submission. Exactly thesame, theUnited States hasalready saidintheletter thatwassenttothe
European Community in1987, andwehavequoted thesevalues inthefootnote thatwehavesubmitted
inthesecond written submission totheUnited States Panel.
739. Forexample, theUnited States hasfixed foroestradiol 120ppt,forprogesterone 3ppband
fortestosterone 640ppt. These arepublicly known andhavebeencommunicated totheEuropean
Community asbeing thevalues thatshould notbeexceeded: thetolerances, thethresholds. Butthen
theUnited States hasreplied thatalthough reliable research methods areavailable fordistinguishing
these levels from background, aregulatory method isnotrequired because under conditions ofuse
theactual increases intheendogenous steroids arefar,farbelow permitted concentrations. Sofor
thatreason theydonotinclude them intheirannual control plan.
740. Mr.Chairman, linked tothatissue istheexplanations were given byDr.Lucier onthefact
thatprobably thealready existing physiological levels arecarcinogenic ofthethree natural hormones,
inthiscaseitwasoestrogens. TheCommunity hassubmitted evidence, which wasnotdiscredited
asfarasIknow, showing thattheincrease oftheriskwasprobably two-fold fromthose residues and
nottwotofive-fold asitisstated foroestradiol intheJECFA Report of1988. Wehavealsosubmitted
evidence about theincreased risksforthepre-pubertal boys-thecalculation waswrong.
741. Thetwoissues thenlinked together andmyindirect question toDr.Lucier would be,according
tohisownestimation thatitmaybeoneinonemillion theriskofadditional riskfrom theresidues
ofthose natural hormones which, forexample, ifwetake thetotal population oftheWT/DS48/R/CAN
Page372
European Community mayleadtoabout 300-350 potential cancers intheEuropean Community. And
ontheother sideweput,thisisalsointherecord, thatthemaximum economic potential benefit for
thefarmers oftheuseofthese hormones ranges between minimum 30andmaximum 80dollars -that
iswhatitisintheliterature. How would youreevaluate theresponse thatisitreally from therisk
assessment, theriskmanagement pointofview, isitreally worth while taking intoaccount thepotential
benefits oftheuseofthathormone inviewoftherisksthatarealready there, asyousaidfortheexisting
levels, andifyouwould takeourlevels thatitisevenhigher. Would youreally, asascientist who
isinvolved intheissueofriskassessment andprobably management ofthatrisk,howwould youlike
toexpress yourself ontheregulatory authority andhowyouwould takethatintoaccount when
legislating?
Dr.Lucier
742. Riskassessment ishardenough, nowyouaregoing toaskmeabout riskmanagement too?
Iamreally notinaposition toevaluate benefits versus risk. What Iknow ishowhormones andother
agents cause cancer andhowtotranslate thatinformation intoasgoodascience-based riskassessment
asispossible. Ireally haveessentially noexpertise interms ofquantifying benefits interms ofwhat
thebenefit might beeconomically orwhat itmight besocially, politically, whatever. Ihave no
experience inthatsoIamreluctant todothat. Iappreciate yourpoint andIthink itisnotatrivial
point, butIamreally notinaposition togiveaninformed answer tothequestion. Myestimates are,
andthere isalotofvariability inthese kinds ofestimates, butgenerally anupperbound estimate of
theriskofbreast cancer, andInarrowed ittothatparticular areabecause Ishould think thatiswhere
thedataisstrongest, would beabout onecancer inclosetoamillion ofpeople exposed tothatbyeating
500grams ofmeatperdayovertheirlifetimes. SoIfeelrelatively comfortable withthatnumber,
recognizing alltheuncertainties thatareassociated withanykindofextrapolated riskassessment and
IwishIcould giveyouananswer interms ofhowthatrelates topotential benefits, Idon'tknow.
Oneinamillion isnotaveryhighnumber ofcourse -itisaverylownumber, butforthatoneperson
whodoesgetcancer itisasignificant risktothem, soonecannever underestimate that,butasmuch
asIwould liketoanswer yourquestion about thebenefits partIreally donothaveabasis onwhich
todoit.
Dr.Ritter
743. Icannot offer anything withregard tobenefit, butIthink there isanimportant point of
clarification here. Intheestimates thatDr.Lucier presented yesterday, Ithink whatyouhavedone
istaken theoneinamillion thathetalked about andmultiplied itbythepopulation inEurope and
fromthatprojected ananticipated increase of350cancers. Ithinkyoushould notethatoneinamillion
istheupperbound. Thenumber could bezerotoo.Theoneinamillion represents, inDr.Lucier 's
opinion, thehighest probable risk,notthelikely probably risk. Butinriskassessment wetalkabout
anupperbound, thatis,thehighest riskthatwecancontemplate fromamathematically derived model
issomewhere inthatrange. Butitwould beincorrect andcertainly misleading, andweseethisall
thetimeinriskassessment, touseasingle number because thenature ofmathematically derived risk
assessment isthattheyprovide arange ofvalues rather thanasingle value. Ithink thatwasthepoint
thatDoctor Lucier wastrying tomake; thattheriskprobably fallssomewhere between zeroandone,
anditwould beincorrect tociteeither zerooronebecause themethodology simply doesnothave
thedegree ofcertainty thatallows youtociteanumber, whichever oneitis,withthatdegree ofprecision
-itisarange.WT/DS48/R/CAN
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Dr.Arnold
744. Iwanted tomake twocomments onwhatyouhavejustsaidinyourrecent contribution. One
thing isimportant, Ithink, forthePanel toknow. Ifyoudesign thestatistical sampling plan, itis
veryimportant whatisthepopulation tobesampled, whatistheareaandIknow atleasttheAmerican
delegation cancorrect meifIamwrong, butIspent many hours withtheirexperts attheFood and
Drug Administration. Atthatyear, USDA, thebasis isanational residue plan. Itcovers allofthe
United States andyoucannot directly compare thisfigure withthefigure oftheEuropean Community
because theplans oftheEuropean Community havetocomply withcertain concepts, butthese are
plans fortheindividual member States. Sotheminimum number required tohaveacertain statistical
certainty, ifyoutakeafigure from theUnited States, andwant tocompare ittotheEC,youhave
tomultiply withthenumber ofmember States; soyoucannot directly compare thesefigures. Atleast
forGermany Iknow thatyourfigures arewrong, butIwould alsobewilling toprovide youwiththe
ECdocument showing thatyourfigure iswrong. Ihavenoexplanation, maybe youcombine allresidue
testing, butforthehormones definitely yourfigure iswrong. Ihavethepaper withmeandIamwilling
either togiveyouthedocument orthereference number: theyarewrong. SointheEC,Ididnot
havethetimetosumupallsamples, butitseems tobeintherange of20,000 to25,000. AndasI
saidyesterday, halfofthesamples aretaken inonecountry sothere areremaining maybe 15,000 or
12,000 fortherestofthemember States. Andifyouthenprepare thiswiththefigures ofthe
United States, itisroughly anequivalent programme. Thatismyconclusion.
745. Thesecond point Iwanted tomake: Iagreed thatintheIARC Report therange ofthis
production, daily production, isbetween 0.4and2.Itstands inthatReport. Butnobody hassaid
thatthefigure usedbyJECFA comes from thisReport. Iwasabletotraceitbacktoapaper given
byDoctor Farber andDoctor Arcos fromtheFoodandDrug Administration in1983attheOIEmeeting.
Icould notgofurther back, soIamnotsurefromwhere thedatacomes, butIcansaytheydefinitely
donotcome from theIARC Report. Itriedtoexplain howsuchsmall differences could happen if
youhaveaverybigrange andonegroup decides tousethemean andtheother decides tousethe
median, thenyouhavealready thisdiscrepancy. From mypoint ofview, itisinthesame order of
magnitude andweshould notspend alotoftimetosaywhoisrightorwhoiswrong. Thisfigure
definitely doesnotcome from theIARC Report.
Mr.Christoforou (EC)
746. Mr.Chairman, Iamafraid Iwillneedtoinsist onthisandIwilltakethetimefrom other
valuable questions butwedidgoback, Dr.Arnold, ourselves onthisissue. Asyourightly tosay
intheReport oftheInternational Office forEpizootics, thearticle byFabre andArkas, theycitethe
article byArgus Engler(?) of1974. Andifyoulookatfootnote 39oftheJECFA Report theycite
exactly thesame article. SoboththeFabre andtheOIEReport, boththeJECFA Report, relies on
thesame reference which is6micrograms per24hours. Whereas theIARC Report of1987 isbased
onthevalues ofBrown which aremore recent andwhich wehavediscussed yesterday -theyarenot
6micrograms per24hours. Wedidthatresearch soIcanshow youthedocuments ifyouwish. It
iswrong theconclusions youdraw.
Dr.Arnold
747. Ihavesaidthefigure doesn 'tcome fromIARC andyouhaveconfirmed. Which isthebetter
figure?
Mr.Christoforou (EC)
748. Well, inourview, weusethefigures theIARC which aremore recent. These figures are
alsodiscussed intheissues ofBrown andtheyarenotapproved. Thatistheconclusion wecandraw.
They were coinciding withthefigures ofwhich Dr.Lucier wasaware aswell. ButIwould also,ifWT/DS48/R/CAN
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wehadthetimeMr.Chairman, liketogointothecomparison ofthenumber ofsamples because we
definitely disagree onthisissuewithDr.Arnold, butthatwilldeprive meagain ofvaluable timewhich
Iwould notliketodo.Weformally disagree, wehavetheprotocols here, forserum wehavechecked
59,000 onlyforthethree natural hormones oftheEuropean Community andforthetotalnumber of
hormones checked intheEuropean Community thetotalamount isjustabout 200,000 samples.
749. Mr.Chairman, Iwould liketocome backagain onthisissue oftheriskthatwasdiscussed
between Dr.Lucier andversion intheplace ofDr.Ritter. Thereason forwhich Iposethisquestion
isbecause thedelegate ofCanada hasmade theshort statement starting thediscussion andhesaid"Is
thislittleriskenough tojustify thedeparture fromtherestrictions oninternational trade" andofcourse
thisisrelated bothtoriskassessment andriskmanagement andtheeffects ofthat. Wehaveprobably
different views whatthemagnitude oftheriskis.Butthese arethevalues wearecomparing here.
Thisriskisinvoluntary fortheconsumers. Weare,ofcourse, aware thatmaybe zerotoonethousand,
onemillion, butitisaninvoluntary riskformillions ofpeople. Thequestion asascientist, ifyou
were, youprobably don'twanttocontinue thediscussion, butIwassimply trying tolinkthistothe
ADIwhich JECFA refused tosetinthiscase, although Dr.Lucier would sayitisfeasible tofixone,
wedoit,theUnited States doesit,buttheydonotapply it,whereas wedoapply it,evenifthethree
natural hormones oftheCommunity areonlyallowed fortherapeutic use.Thenatural hormones are
notallowed tobeusedforgrowth promotion, stillwecheck forthelevels ofthose 59,000, asIsaid,
intheEuropean Community. Thisisaninvoluntary risk. Why should theconsumers takesucha
risk,probably itslow,butitisthere arisk.
750. Thesecond question ofcourse andIwilllinkthistowhat IsaidtoDr.Arnold thatrelates
totherapeutic use.Hehasmentioned twice theevaluation made bytheInstitute, theagency inLondon
ofoestradiol which isalready published asaregulation andofprogesterone which isonitsway. But
Dr.Arnold didnotmention probably alltheconditions which areimposed fortheuseoftheseoestradiol
astherapeutic instrument. Weknow thattheyhavetobeadministered byaveterinary ifitistherapeutic
use,weknow theanimal hastoberegistered andidentified andweknow these animals donotgointo
thefoodchain because theyarenotslaughtered. Wehaveprovided evidence tothePanel thatthis
percentage isnotmore thanone,andwehavemore evidence which willprovide tothePanel from
other member States which havenotreplied bytheendofJanuary which indeed demonstrates that
therateisnotoveronepercent. These animals might havebeentreated, aswassaidbyDr.André,
oncefortherapeutic orzootechnical treatment. Butthere isinatime-lapse between thetreatment and
when wedecide forthatonepercenttoslaughter itandtosendittothefoodchain.
Chairman
751. MayIaskyoujusttosubmit succinct questions totheexperts andnottoplead. Ithink this
isnotthehourtoplead. Youhaveanother goonpleading tomorrow, butjustplease dosubmit questions
andmake thebestuseofthisvery, verylittletimewestillhaveavailable thisday. Theexperts are
flying home andthentheyaregone andweonlyhavecorrespondence, andIhaveawhole listof
questions which aresustained andIwillcome inwiththesequestions at6o'clock andthatismydecision.
Mr.Christoforou (EC)
752. Theprecise question is,therapeutic treatment, weknow whatitis-theword explains it-would
youthink because oftheneedtohavetheanimals treated fortherapeutic purposes, anextrapolation
canbemade ofthatandallow theuseofthese hormones forgrowth promotion. Isthisacomparable
example? Isitcomparable tosaythatbecause theyareusedfortherapeutic purposes theyshould also
beallowed tousefor.Is,inother words, thepotential risktoconsumers thesame fromoneandthe
other situation ifyoutakeintoaccount theconditions under which thetherapeutic useisallowed to
theCommunity? Thisisinparticular toDr.McLean andtoDr.André.WT/DS48/R/CAN
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Dr.McLean
753. Theonlyreply thatIcanmake isthatyouhavemade much oftheillegal useofhormones
ortheabuse oftheuseofhormones andso,therefore, onewould suggest thatveterinarians aregoing
tobenobetter ornoworse thantherestofthepopulation. Iwould remind youthatitisoften the
casewhere theveterinarian leaves thematerial behind foradministration bythefarmer forlatertreatment
andsothatisapossibility -Icansaynomore.
Mr.Christoforou (EC)
754. Weareallsometimes inourlifeillandwemayneedtreatment byadoctor. Areyousuggesting
thateventhattypeoftreatment should notbemade because Isometimes havetobetreated fortherapeutic
orzootechnical reasons. Either way, whatwecallzootechnical fortheanimals, ifawoman cannot
getpregnant shewould havetogotoadoctor forthattreatment tobemade. Itiscomparable, itis
justonce, aswesaid,itisdone. Doyoureally think thisisareason enough initself toextrapolate
andallow theuseofthehormones asgrowth promoters? Thatistheissue. Weallgetill,butfrom
thatwhatistheconclusion oneshould draw?
Dr.McLean
755. Itisverydifficult toanswer thatquestion ifyouareasking metoextrapolate Iwould suggest
toyouthatgiven thepotential formisuse andthesmall amount ofmeat thatmight beeaten bythe
average person intheEUfrom imported meatthentheriskwould bejustabout thesame.
Mr.Christoforou (EC)
756. Thesecond question relates totheargument wehavebeendiscussing about. Wegetincreased
values ofallthese natural hormones fromanumber ofsources. Oneofourexperts hascalled thesea
ofoestrogens which areexisting inourdaily lifeandIwould liketogivethefloor toDr.Liehr to
make acouple ofcomments andthenprobably askoneprecise question.
Dr.Liehr (EC)
757. Mr.Chairman, yesterday weheard Dr.McLean talkabout andIquote him"Weliveinasea
ofhormones andthathormones areinourdiet"andhealsosaidthatitisdifficult todetermine where
ourhormone burden comes from. Alsotoday there werereferences early onindiscussion about the
various hormones thatweareexposed to.
758. Iwould liketobring toyourattention animportant distinction here. Oestradiol, testosterone
andprogesterone arehormones thatarecirculating within allofusandcarefully controlling endocrine
functions within allofus.Theproduction ofthese hormones within mammalian systems, including
humans,areverycarefullycontrolled,thedispositionisverycarefullycontrolledbecausethesehormones
verycarefully controlled reproductive function andavariety ofother functions thatIcannot goand
donotwanttogointohere. Atelevated levels suchhormones maybeharmful -wearetalking about
breast cancer riskandalsoDr.McLean thismorning talked about extratestosterone shutting offsperm
production andlowering malefertility. Many compounds, including phyto-oestrogens forinstance,
insoyaproducts,haveoestrogenicactivitybutthereisavastdifferencebetweenhormonesinmammalian
systems andcompounds withoestrogenic activity suchasforinstance inphyto-oestrogens. Differences
arethattheyaredifferent compounds withdifferent activities -oestrogenic activities ofmany ofthese
compounds are1,000 to10,000-fold lower thanthatofthemammalian hormones. There isreally
avastdifference between acompound thathasoestrogenic activity andtheactual hormone. Some
ofthese compounds have alsobeenshown tobeoestrogenic andothers areanti-oestrogenic. As
Dr.Lucier saidalittlebitearlier on,thisisaveryactive areaofresearch andIknow heisinvolved
inthis,nevertheless, itisobvious alsothatonbalance between oestrogenic andanti-oestrogenic activityWT/DS48/R/CAN
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itmaybebeneficial andmuch ofthisisnotknown atthispoint. What isclearthough isthatacompound
withmuch, much lower oestrogenic activity thananatural hormone introduced intoasystem with
oestradiol insuchasystem, suchaphyto-oestrogen mayactually beanti-oestrogenic, oractinan
anti-oestrogenic manner, because itcompetes fortheoestrogen receptor. Anindication ofthisisthe
lowbreast cancer riskinpopulations where highsoyabeandietsareconsumed. Sotoimply thatthe
administrationofthemammalianhormoneatlowlevelsislikeapplyinganantibioticoraphyto-oestrogen
isreally inadmissible. These aredifferent compounds, theyhavedifferent spectrums ofactivities and
theyshould beweighed ontheirownbenefits.
Mr.Christoforou (EC)
759. Isthere notadifference between thehormones inmammals andphyto-oestrogens indiet,in
physical, chemical andhealth effects? Isthere adifference between these three?
Dr.Ritter
760. Imaybeabletomake thisshort. Thisanswer isyes. There aredifferences.
Chairman
761. Could youperhaps saywhy?
Dr.Ritter
762. Well, Ithink, ashasbeenquitecorrectly pointed out,therearedifferences inbinding capacity,
there aredifferences instructure, there aredifferences infunction. Clearly aphyto-oestrogen was
never invented tohaveaphysiological function inamammal. SoIagree witheverything you'vesaid
except thattheydonotcontribute much totheoverall risk. ThatpartIamlesscertain about thanyou.
Thattheyaredifferent intheirstructure, thattheywereclearly developed through evolution tohave
afundamentally different purpose, Ithink itisaninescapable truth. Butthattheydonotcontribute
torisk,Iwillnotengage youinadebate now, about breast cancer statistics incountries where soya
beanintake forexample ishigh, except tosaythatitisnotquiteasclearasyoupresent it.ButIthink
theshort answer, without labouring itinthelimited timeavailable, isofcourse there aredifferences
inthese different categories ofoestrogens.
Dr.Lucier
763. Iwillquickly addtothat. Iagree withwhatyouhavesaidaswell. There aredifferent binding
proteins anddifferent receptors thatarenowbeing discovered fordifferent agents. There isa
beta-receptor thathasjustbeendiscovered andsoforthandthisisadifferent binding spectra thanthe
receptor thatwe'veallcome toknow andlove. Theinteraction issue isavery complex one.
Nevertheless thereisalotofinformation inthepublished literature oncellsystems andin-vivo systems
thatcertain mixtures ofexogenous hormones doproduce stimulatory responses thatarecharacteristically
oestrogenic. Sointotalthese things areproducing anoestrogenic response. Exactly themagnitude
oftheoestrogenic response ishighly uncertain.
Mr.Christoforou (EC)
764. Thenextquestion relates towhatthelawyers among ourselves calltheissue ofconsistency
andinthatcaseitwasdiscussed byreferring toanumber ofsubstances. Iwilltouch onlythesubstance
ofcarbadox. Thediscussion waslively butwedidnotexplain theconditions under which carbadox
isallowed tobeadministered intheEuropean Community. Carbadox doesnotactasadirect growth
promoter asthenormal hormones wearethinking about. These growth-promoting effects areonly
because itcombats thebacteria andithelps theintestinal floraandindoing thatithelps thegrowthWT/DS48/R/CAN
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oftheanimal. Thehormone doesnotexert anyother action apart helping thegrowth promotion of
theanimal. Andthere arenoother readily available substances onthemarket which candothesame
thing. Itisadministered onlytopiglets andthere isa28-day obligatory withdrawal period. From
thatdiscussion andbecause theCommunity allows theuseofcarbadox under theconditions andeven
stricter conditions thanthose recommended byCodex. Iwasleftwiththeimpression thatprobably
because theCommunity allows theuseofcarbadox, should itallow alsotheuseofhormones, because
attheendthetwotypes ofsubstances forthesame risktohuman health, thatiscarcinogenicity. What
should betheparadigm? Because weprohibit thehormones should wealsoprohibit carbadox orbecause
weallow carbadox wealsoshould allow thehormones? Thisisanimportant question. AndasIsaid,
wedorespect exactly theconditions ofJECFA astheyarerecommended. There isnoriskbecause
wehavebeendoing allthesamples andthechecking andthere isnoreported caseofexcess. Sodo
youthink, andIaddress thistoDoctor Lucier because attheendthequestion ofwhatareweexactly
comparing wascritical. Doyouthink thiscomparison isreally meaningful andshould itbetaken into
account intheglobal riskassessment ofthehormones inthiscase?
Chairman
765. Ithinkthequestion should belimited tothescientific distinction oftheagents andnotthepolicy
options which youinvoked aswell, ifyouagree?
Dr.Lucier
766. Ihadn'theard thatpartofthequestion anyway, Mr.Chairman. Iunderstand whatyouare
saying thatcarbadox isnotusedasagrowth promoter, itisusedasananti-microbial agent, soits
purpose, itsuse,ismuch different thanforthehormones inquestion. Ontheother hand, itis,and
Ionlysawthecarcinogenicity dataonittoday andmynext-door-neighbour hasgone andleftwith
it,soIcannot refertoitagain, butitwasafairly potent carcinogen -itwasacarcinogen atmulti-sites,
atdoses wellbelow themaximum tolerated doseanditisgenotoxic, soitisnotanagent thatyouwant
toexpose alotofpeople to.Thatismyonlypoint. SoIthink strict attention needs tobegiven to
theavoidance ofresidue levels ofcarbadox given theavailability ofthatcancer data.
Chairman
767. IfIamcorrect, theagent works assisting thefloraanditisnotreally having hormonal effect.
Would youconsider thistobeacritical distinction between thetwoagents ornot?
Dr.Lucier
768. Itdepends, itisadistinction, theyareusedfordifferences purposes. Idonotknow howto
sayitbeyond that. Thepurposes arevastly different. Nevertheless, theyarebothpresent andboth
mayhavetheirownrisk. Theriskofcarbadox, ifresidues arepresent, arelikely greater thanthat
ofsome ofthehormones inquestion.
Dr.McLean
769. Ithink itwould beuseful forthePanel toknow thatthere isanother drugrelated tocarbadox
-olaquindox, andwhilst JECFA hasreviewed it,ithasnotsetMRLs andADIs because thedatapackage
isincomplete. Butnotwithstanding Ibelieve itisusedintheEUanditisjustaseffective, ithasa
mode ofaction thatissimilar, inother words, interfering ormodifying themicrobial population and
sotherefore itisanalternative anditisjustaseffective andofcourse there areother anti-microbial
agents thatareusedinanumber ofother countries asgrowth promotants thataresubstitutes forboth
olaquindox andcarbadox, suchasthetetracyclines asanexample.WT/DS48/R/CAN
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Chairman
770. Butcantheagent becompared withthehormonal agents orisit...
Dr.Ritter
771. Areyouasking thequestion thatyouareasking when youaskabout thedifference being
important between carbadox, forexample, areyouasking thedifference inriskstohuman health?
Chairman
772. Theproblem isthatlegally theagreement requires consistent policies. Oneargument goes
thatyouallow thisagent butyoudonotallow theother oneandofcourse youcanmake thisargument
ifthese arecomparable agents. Itisimportant forustoknow whether from thescientific point of
viewyoucancompare these agents andputthem onthesame level, knowing thattheoneaffects the
hormonal household andtheother onethemicrobiological situation inthestomach. Socanwecompare
thetwoandputthem onthesame level andaskforthesame policy under theagreement oristhat
acompletely different story. Carbadox andtheother oneisolaquindox.
Dr.Ritter
773. ThehourislateandIamgoing togooutonalimbandeventhough anumber ofushave
consistently saidduring thedaythatwefeeluncomfortable withdrawing comparisons, ifitwould assist
thePanel, carbadox isagenotoxic carcinogen. Ithink there arefewpeople inthisroom whowould
disagree withthatconclusion. There isverymuch debate, some ofwhich youhaveheard inthelast
dayortwo,astowhether ornotthehormones areindeed genotoxic carcinogens. Toputthisinto
perspective, within thetoxicological community, wewould attach greater concern toacompound which
wasagenotoxic carcinogen thanwewould toonethathasbeenreferred tointhelastcouple ofdays
asepigenetic. Carbadox issuchagenotoxic carcinogen. Ipersonally would beinclined tosaythat
theevidence foroestradiol, forexample, being agenotoxic carcinogen, isweak, whereas inthecase
ofcarbadox itisdefinitive andifonehadtoputonaranking scale where youwould attach greater
concern orgreater importance, Ithink most ofusinthescientific community would argue thatwe
would probably haveaheightened levelofconcern forgenotoxic carcinogens thanwewould forsome
other class. Idonotknow ifthatassists.
Chairman
774. Yes,itdoes. Would youliketospeak onthatpoint?
Dr.Arnold
775. Dr.McLean mentioned olaquindox -itisalsousedintheEC.Itisinthesame annex tothe
feedadditives directives. Itischemically similar tocarbadox butthere areinteresting differences.
Olaquindox isgenotoxic inaverylarge number oftests, butinthecarcinogenic studies, which were
available toJECFA, itdidnotshow carcinogenicity. There wasnoincrease ineither benign ormalign
tumours. Thatisastrange finding, butitisreally genotoxic andIwould sayinmore thantentest
systems. Thesubstances usedintheECasgrowth promoters could replace carbadox theoretically,
unfortunately theresidue situation isnotclear. Wehavenomarker residue, wearenotabletoset
anMRL, sowehavenomeans tocontrol theuseofthissubstance. Buttheoretically itcould replace
carbadox anditisinthesame annex tothedirective.WT/DS48/R/CAN
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Dr.Lucier
776. Inrelation tothatpoint andthepoint thatDr.Ritter made, Idonotgetsoconcerned about
thedistinction between genotoxic andnon-genotoxic. There aregenotoxic non-carcinogens andthere
arenon-genotoxic carcinogens. What Iprefer tolookatisthestrength ofthecarcinogenic response -
what sitesareaffected, what number ofsites, whether itoccurs inmultiple species, orinmultiple
organs. SoIlooked atthecarbadox carcinogenicity dataIwasimpressed forthenumber ofsitesthat
were affected where tumours appeared, themagnitude oftheresponse, theywere veryhighovera
background andtheyoccurred inmore thanonedose; suggesting thismight beasensitive effect.
Ontopofthatisgenotoxic. Butmyconcern wasnotsomuch forthegenotoxicity, itwasthefact
thatthetumour response wasaverystrong oneforcarbadox.
Dr.McLean
777. Onepoint thatisgermane, inmycountry carbadox isbanned andisbanned onoccupational
health andsafety grounds -inother words, wehavemore concern withthose thathavetomixitin
withthefeedandfeedtothepigs,thanwedototheconsumers oftheproduct andsoitisanoccupational
health hazard.
Dr.André
778. Iamnotaspecialist ofcarbadox butIamhappy tohearthis,because Iunderstood thismorning
orthisafternoon, thatcarbadox isacarcinogenic compound, butitisnotaproblem touseitbecause
itisimmediately andveryfasttransformed inaninnocent metabolite. Therealriskisforfarmers
andformanufacturers -itisnotformeatorforpigsormeatcontaining carbadox, meatcannot contain
carbadox residue, itisokay. Justtoclarify.
Mr.Christoforou (EC)
779. Itisunfortunate thatthisisgoing tobethefinalandprobably yourfinaldecision onthisissue.
Ifitisindeed finalquestion itisregrettable because wedohavemany questions. Then Iwould only
comment onthatDr.Ritter saidoestrogens areweak carcinogens -thatisthestatement Iheard -weak
genotoxic, could youplease restate?
Dr.Ritter
780. What Isaidwasthattheavailable evidence inthecaseofcarbadox intheexample Iwasdrawing
isthatcarbadox wasgenotoxic inavariety oftestsystems. Thedataisoutlined inthe1989 JECFA
Report. What Isaidwasthatthegenotoxicity ofoestrogens isstillopentosome speculation. That
iswhatIsaid.
Mr.Christoforou (EC)
781. Ithought weheard theword "weak". Butifitisso,wehavealready, anditispublished,
thattheIARC, theInstitute onCancer Research, hasclassified oestrogens ingroup 1,which isgenotoxic
andcarcinogenic.
Dr.Ritter
782. Iamgoing topresume thatyouaredirecting thatquestion tome.Ithink weareconfusing
apples andoranges. Thatoestrogens havethepotential tobehuman carcinogens isabsolutely true.
Idonotthink there isanybody whowould argue withthatwhoisallfamiliar withthediscipline.
IthinkDr.Lucierexplainedthatyesterday.Thereisnoquestionthatweknowthatcirculatingoestrogens
inawoman 'sbody haveaprofound impact onherriskforbreast cancer. ThisisofnoquestionWT/DS48/R/CAN
Page380
whatsoever. What wehavebeendiscussing hereforthelastcouple ofdaysiswhether thelevels that
arepresent asaresult oftheuseofthese products ingrowth promotion aresufficient toconstitute a
meaningful risk,andwedefine meaningful asbeing somewhere intherange ofoneinamillion. This
hasbeenthenature ofthediscussion forthelastdayortwo. Notthatatsome doseoestrogens are
capable ofcausing cancer. IfIhaveimparted theimpression thatsomehow oranother Idoubted that,
letmecorrect it.Tobeclear, oestrogens arehuman carcinogens. Inever meant toimpart anyother
impression. ButIhavealsoindicated thatinmyviewtheoestrogens present atthelevels thatwould
bepresent asresidues asaresult oftheiruseasgrowth promotion constitute, inmyopinion, no
significant riskatalltothehuman population.
Chairman
783. Thisnowbrings ustothelaststage ofthishearing andIamsorry wehavetoadvance and
Iwould really justliketogetusthrough these questions asrapidly aspossible. Wehaveprepared
anumberofso-calledadditionalquestionswhichwerecirculatedwiththePanelandalsowithdelegations.
What Iwould intend todoistotouch upon them orally andthenseeintheendwhether itmight be
feasible tomaybe havethem doneinwriting inorder tobefullyaccurate. ButIwould liketohave
theopportunity ofdiscussing them orally since youarehere.
784. Thefirstquestion really addresses apoint wehavenottouched upon, which isthedifference
inhealth risksofthenatural andartificial hormones. Isthere adifference intheriskofusing natural
hormones ortheartificial hormones? Inother words, cantheylegally beclassified inthesame group
ordoyouseethere ground fordistinguishing these agents?
Chairman
785. Justtotakethefloor asitcomes andthenwehaveagood debate.
Dr.Lucier
786. Letgivemeastabatthat. Notthatwehaveananswer toallthequestions, butforthenatural
hormones wehaveagreat wealth ofinformation about howtheywork indifferent cellsandtissues
ofthebody. Thisisinthepublished literature. Weknow alotabout, asyouhaveheard, about how
theygoabout producing cancer aswellasotheradverse health effects. Weknow lessabout thesynthetic
materials. Nowthesynthetic materials aredesigned tomimic thenatural hormones. Sotheywillhave
onesetoftheirbiological properties, willbeverysimilar tothose forthenaturally-occurring hormones,
thatistheability tointeract withthereceptor system andstimulate thesame kindof,sayoestrogen
ortestosteroneresponsivesystemsthatthenaturally-occurringonesdo.Butinaddition,thecomplicating
factor isthattheirstructure isdifferent. Sotheymaypotentially havebiological properties inaddition
tothehormonal properties. Andthatiswhere anylevelofconcern would come in.Nowtogetany
ofthese synthetic materials registered foruse,theyhavetogothrough thesignificant testing protocol
todetermine whether nottheycause cancer orproduce other kinds ofeffects. Thatinformation is
notavailable from theregulatory agencies because itisproprietary. Somuch lessofitisinthe
peer-reviewed published literatures. Youdon'thaveasmuch information inpeer-reviewed published
literature forthesynthetics asyoudoforthenaturally-occurring ones.
Chairman
787. Thank youverymuch. Anyother views? Addition? Itakeitifthereissilence thatyouagree?
Otherwise youwould justoppose orclarify.WT/DS48/R/CAN
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Dr.Arnold
788. Itisadifficult question. Ilargely agree, butifforexample, Itakethemolecular structure
andlookatthings, Dr.Liehr hasalready described andDr.Cavalieri andImust saythispotential
isnotassociated tosuchextent withzeranol. Sodepending onwhat youarelooking, youcould come
totheideathatsynthetic hormones aresaferthanthenatural andifyoulookatother things youcould
come toanother conclusion andthatistheproblem.
Chairman
789. Soyouwould agree weknow less,youknow about them thanthenormal ...
Dr.Arnold
790. Weknow lessabout thesynthetic buttheymight besafer thanthenatural.
Dr.André
791. Ashort point. Ithink thefactthatCodex didnotestablish MRLs forthethree naturals in
comparison withtheothers isnever mindthattheyaresaferornot.Theproblem isthatCodex establish
noMRL forthese natural hormones onthebasis first,thattheyarenatural, andapriori, thatifthey
arenatural, theyarelesstoxic, Ithink, maybe.Andtheyarethought so.Andthesecond reason
isthattheresidue levelhasbeendemonstrated tobewithin thephysiological range. Andtaking account
these twofacts, theydecided nottofixMRL butnotonsafety basis.
Chairman
792. Thank youverymuch. Yes.
Dr.McLean
793. Very quickly, theevaluation process, theformal evaluation process ofveterinary drugs is
designed toreach apoint where youeffectively reduce therisktozero. Now inthecaseofthe
naturally-occurring hormones, itwasbelieved thattheadditional amount thatwould come fromingested
foodwould notcontribute totheoverall burden inasignificant wayandsothatriskwaszero. Inthe
caseofzeranol andtrenbolone, thenanacceptable dailyintake wasset,andagain, providing thatwasn't
exceeded, theriskwasessentially zero. Andthesecond point Iwould liketoaddthatthetwosynthetic
hormones havebeensubjected toaformal toxicological evaluation process designed tobring outthe
toxicity. Andsotherefore, insome ways, those processes, which arecomplete forzeranol andfor
trenbolone, areidentifying thetoxichazard andbringing itout.Andwhilst Iaccept thefactthestudies
arenotpublished intheopen literature. Themonographs thatJECFA prepares areopen literature
andthere areahundred orsopages ofmaterial relating nottoeachofthem, tobothofthem, andthat
isavailable forperusal andscrutiny. They arealsoincluded inthatmaterial, itisfrom theopen
literature, although thatisnotlarge. Andso,thatisthecouple ofadditional points Iwould liketo
make, Mr.Chairman.
Chairman
794. Thank youverymuch. Ithink wedon'thavetoaddress questions 2and3because, wehad
anextensive discussion hereoncarbadox andolaquindox, justaminute ago.Iliketoturntoquestion 4.
Arethere anyqualitative chemical orother differences between thethree natural hormones indispute
inthehuman being, depending onwhether these hormones arebeing endogenously produced bythat
human being; secondly areadded tothehuman being because ofconsumption offoodendogenously
containingthesehormones,orthree,ofmeattreatedwiththesehormonesforgrowthpromotionpurposesWT/DS48/R/CAN
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orfour, ofmeattreated withthese hormones fortherapeutic purposes? Doanyofthese chemicals,
orother differences, ifany,poseanadditional risktohuman health? AndifProfessor André could
elaborate onhisthesis onthenatural hormones added tohuman beings having different metabolites.
Dr.André
795. Veryquickly. When natural hormones areadministered toanimals firstasesters, asimplants
orbyinjection, theydon'tfollow inthebody same route astheendogenous ones. Because the
endogenous onesaresecreted inonegland, circulate andaremetabolized inanother partofthebody.
Sotheycannot beexactly compared. There aresmall differences intheanimal. Sothatthese animals
might produce different metabolites withsame hormones injected astheycould dowiththeirown
hormones. Forexample, theycould produce various proportions inconjugate forms. Assulphosteroids
instead ofglucurono steroids, forexample. After this,inthemeat, youmayhavedifferent varieties
ofmetabolites. When human beings areeating these metabolites, theyareeating different compounds
fromnatural hormones astheirownendogenous natural hormones. Following myexample, itcould
bethathuman beings absorb some sulphosteroids andithasbeensaidthisafterthatanewinformation
appear nowontheroleofsulphosteroids inthehuman brain. Sothatyoucannot exactly assimilate
thenatural oestradiol, progesterone andtestosterone ofhuman beings withhormones theyareconsuming
infood. Ihopetobeclear enough.
Chairman
796. Would youliketotalkonthisquestion?
Dr.Ritter
797. Nottoprecipitate alengthy debate, buttosimply present analternative, ifyoulike. Tothe
bestofmyknowledge andagain thatinformation waspublished intheEuropean Conference onGrowth
Promotion, aswell. Tothebestofmyknowledge, ifthestructure ofthehormone thatisifweare
talking about thesame hormone which isproduced endogenously orexogenously, ifintroduced
exogenously, theyentertheidentical pathway. Andfromthatmoment intimetheyareindistinguishable
tothebody. AndIsayIcanprovide thePanel withpublished references which support thatview.
Chairman
798. Butisitfairtosaythatthere aretwodifferent views inscience?
Dr.Ritter
799. Ithink itisfairtosaythatthere areprobably 30.Asmany...
Chairman
800. Asauthors?
Dr.Ritter
801. Youknow thestory ofthetwo-handed scientists: ontheonehandandontheother. Lawyers
areoften looking forone-handed scientists.WT/DS48/R/CAN
Page383
Dr.Lucier
802. There isprobably some small differences intheexact pattern ofmetabolites orbreak down
products resulting fromaslightly different route ofexposure. Thismight beexpected because ofthe
waytheymove through thebody. Idon'tthinktherewould bequalitative differences inthemetabolites.
There might besmall differences inthepattern ofmetabolites. SoIthink that'swhatDr.André was
saying. Idon'tbelieve thatthisdifference inpattern ofmetabolites would betoxicologically significant.
Chairman
803. Thank you. Would you...
Dr.McLean
804. Ijustwanttoconcurwiththatview.Therecouldbesmallqualitativeandquantitativedifferences
butthere would benoeffect onhuman health duetothose small differences, within thebiological
variations, sotospeak.
Dr.André
805. Ontheopposite, youcannot besurethattheyhavenot.
Chairman
806. That'snotanappropriate scientific method!
Dr.McLean
807. JustallIamreally saying isthatIaccept thefactthatthere arequalitative andquantitative
differences. Ibelieve thatdemonstrate anysignificant effect would notbepossible anditisunlikely
thatitwould bethere.
Chairman
808. Ijustwanttosay,youdon'thavetoagree. Iamnotputting adealtogether. Thequestion 5
isbasically justaquestion ofclarification about thenotion ofnormal physiological range. Ifyoucould
comment onthisquestion, whether itdoesrelate totherange inhuman beings orinanimals? Then
thelatter partofthequestion, theimpact onthethreshold approach really goesoverintoquestion 6,
which thenIwould liketoaddress toDr.Lucier.
Dr.Lucier
809. Thepoint thatIwastrying tomake is,andthishasbeensaidnow, Ithink, many times and
nooneseems todisagree withit,thattheamount ofhormones naturally circulating inthebody are
infactcarcinogenic. There isawealth ofinformation inthescientific literature, bothexperimental
aswellashuman studies, todocument this. Nowwhen anadditional molecule comes intothebody
adding tothatburden, itwillnotbedistinguished fromthose other hundred thousand molecules you
puthereinthequestion. Instead ofonehundred thousand molecules of17betaoestradiol circulating
there willbe100,001 andthebiological systems won'tdistinguish thatonefrom theother hundred
thousand. Sointhatsense theissue ofthreshold isirrelevant, since wearealready dealing withthe
carcinogenic dose. Weknow thatifathreshold exists, ithasalready beenexceeded. Soadding that
additional molecule would addasmall increment torisk. Averysmall increment ofrisk,because
thebodywon'tdistinguish thatmolecule fromanyoftheother naturally-occurring ones. Andtherisk
assessment thatItalked about isreally based onthese relative proportions ofmolecules, recognizingWT/DS48/R/CAN
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thatthethreshold ifoneexists, ithasalready beenexceeded. Andthatwasthebasisofmyargument
thatthethreshold issuewasirrelevant here. Because evenifitdidexist, ithasalready beenexceeded,
bythewoman 'snaturally-occurring hormones.
Chairman
810. What isofinterest tothePanel isreally what doesthismean fortheentire concept ofthe
threshold under which themaximum residue levels andtheADI. From yourpoint ofview, ifyou
takethistotheend,would thismake thisapproach redundant? Thisiscontained inquestion 6and
Ithink itisaconceptually veryinteresting point. Youknow, isthisachallenge tothethesis thatif
wecandefine these levels whatwedobelow issafeandevenwhatwedoabove itisprobably safe
foralongtime.
Dr.Lucier
811. Anyacceptable daily intake willnotguarantee zerorisk.
Chairman
812. Soyouwould challenge thatbelow itwecantalkabout asafety ...
Dr.Lucier
813. Inother words anyadditional incremental increase beyond wealready have, itwould be
reasonable toassume thatanadditional riskiscreated. Soanacceptable daily intake could notbe
established thatwould guarantee zeroriskfortheoestrogens. Because wealready know, again, that
weareatthecarcinogenic levels, sotheassumption isthatanadditional molecule addupvery, very
small incremental increase inrisktothat.
Chairman
814. ButIamcorrect tounderstand thatthemainstream, thetraditional understanding, isthatif
weoperate within these limits, wearesafe.
Dr.Lucier
815. Well, whatthatconcept wasdeveloped forwaslooking atmolecules which wenormally do
nothavepresent inourbodies. Soforsome types ofcarcinogenicity youcanestablish adosebelow
which youarereasonably confident thatnoeffect canoccur. Andthat'swhatathreshold is.Incases
youhaveinaddition toanalready endogenously acting mechanism andweknow wehaveithere, the
issue ofthreshold isreally anirrelevant one. Onemaysetanacceptable daily intake asapolicy.
Butthatpolicy doesnotguarantee zerorisk.
Dr.McLean
816. Thedifficulty withthehormones inmeat, thenaturally-occurring onesisthattheyarealready
there inmeat. Andsotheveryactofeating meataddsmore hormones. Andsotherefore thatisa
risk. Andperhaps onewould therefore, ifyouwant toeliminate thatrisk,youwouldn 'teatmeat.
Buttheargument Ithink iswhether theextra amount produced ortaken inbywhatisalready there
normally plusthesmall increment duetothetreatment, isasignificant extra risk. Andwithnormal
chemicals when wesetanADI, theyarenotnormally inproduce. Andsotherefore, youcansaywell
it'snotthere andyoucanhavethatsmall increase andtheyarenotnaturally occurring. Soit'seasy
tosetanADI. Butwiththecaseofthehormones, theyarenaturally there already andit'sdifficult
tomeasure whattheADIis,because thelevels ofincrease arequitesmall inrelation towhatisalreadyWT/DS48/R/CAN
Page385
there inmany cases. Imean ifyoulookatprogesterone inthenormal cycling cowandtheamount
thatyouaddisvery, verysmall inrelation tothetotal. Soit'snotapractical consideration andIthink
that'swhere wearehaving thedifficulty. Notbetween thecolleagues, buttheconcept ofmanaging
risk.
Mr.Palecka
817. Thank youverymuch, Mr.Chairman. Perhaps justtobeonehundred percentsure...It
means thatlooking atthisproblem quite likely. Ifthere arecabbage eaters oreggseaters, whomay
perhaps addsome more molecules thanoneincaseofeating thehormone meat, itmeans thatthey
maytheoretically through alinear increase beexposed ...more tosaydangerous orthreats, thenfor
example, those whoeathormone containing meat. There aredifferent diets, forexample, youknow.
Such as"cabbage eaters" or"eggs eaters", that'swhatIhadmind.
Dr.McLean
818. Orthose thatdrink milk...Youarejustadding totheoestrogen burden. Andwhether you
takeitinmeatwiththatlittlebitextraadded fromgrowth promotion which isdifficult todetect because
itsitsinarising andfalling normal levelandifyoutakeasample ofmeatoutthere, fromthebutcher
andbring itin,youcannot really saywhether thatmeathasbeentreated ornot.Because thedifference
thatyouaddisburied inthenormal range. Therefore, when youeatit,youaddthatlittlebit.Now
incaseofeggsorparticularly, butter andcheese, forexample, thathavegotalotoffatinthem, then
youtakethose hormones inanywayandtheyarequitehighwhen youcompare themonaweight basis
withmeat, particularly withtreated meat.
Dr.Lucier
819. Putitadifferent way. Forevery million women aliveintheUnited States, Canada, Europe
today, about a110,000 ofthose women willgetbreast cancer. Thisisobviously atremendous public
health issue. Ofthose 110,000 women getbreast cancer, maybe several thousand ofthem arerelated
tothetotalintake ofexogenous oestrogens fromevery source, including eggs, meat, phyto-oestrogens,
fungal oestrogens, thewhole bodyburden ofexogenous oestrogens. Andbymyestimates oneofthose
110,000wouldcomefromeatingmeatcontainingoestrogensasagrowthpromoter,ifusedasprescribed.
Does thathelp?
Chairman
820. Thank you. Could Ifollow uponthis. Inthelightofthis,doyouconsider theMRLs for
thesynthetic hormones adequate?
Dr.Lucier
821. From myreading oftheinformation thatIhaveseentheMRLs arederived bylooking at
hormonal responses inmonkeys. Andthereisaseries ofmeasurements theonegoesabout todetermine
those hormonal responses. Ithink inanycasethatwearetalking about carcinogenicity datahasnot
beenusedexcept theMRL. Ithink thathasbeenbasically ahormone derived response. Ithink in
thecaseoftrenbolone, there wasweak carcinogenic response. Andagain correct meifIamwrong,
andthatwasessentially disregarded inestablishing theADI. Inthecaseofzeranol, itthinks itwasn't
really considered atall,therewasaweak carcinogenic response thattobeduetothehormonal activity
oftheagent. After having saidthat,weheard fromDr.Metzler yesterday thatthere isaDNA adduct
which isofzeralenone, which isastructural analogue ofzeranol inthemetabolic chain ofit.Now
thatDNA adduct ispartofthezeralenone bound covalently toDNA, andforsome chemicals thisis
anearlystepinthecarcinogenic response andanearlystepinagenotoxic response thatinitial binding
covalently toDNA, sowhen thecellreplicates thatadduct isfixed intothe[?]orcellular mutation.WT/DS48/R/CAN
Page386
Ifthemutation occurs inacritical target gene, itcould goontoproduce cancer. Andthat'sthewhole
concept behind theideathatgenotoxic carcinogens needtobeclosely regulated. Nowzeranol isnegative
intestforgenetic activity thatlookattheability toproduce mutations. Yetthisadduct hasbeen
discovered, apparently, andthere issome questions about exactly whatitisanadduct of.Ithasn't
shown tobeclearly related tothezeralenone. SoIdon'tknow, witha100percentcertainty ofthese
acceptable MRLs arecorrect. ButIseenoreason tostrongly dispute them atthispoint interms of
thezeranol. Theonewithtrenbolone causes mealittlebitmore concern. Trenbolone ispositive in
celltransformation assays, inother words, itiscapable oftransforming cells. Ithink therearecouple
ofstudies thathaveshown that. Andthat'sindicative of,itisawaythatpeople screen forpotential
carcinogens, when theyseethisresponse itraises asortofaredflagtogoonandlookforthe
carcinogenic activity ofacompound thatdoesthis. Sothatraises anissue withthecarcinogenicity
studies thatIguess were conducted bythecompany whorequested thatthisbeused. Now asI
understand, thecarcinogenic studies wereessentially negative. Thatthereweresmall increases inliver
tumours. Isthatcorrect? Ithink there weresmall increases inlivertumours thatwereseen. Ithink
theissue oftrenbolone should belooked atperhaps alittlemore closely fortheMRL, inmymind.
Iammore comfortable withtheoneforzeranol. It'salong-winded answer without being much of
ananswer, butittriestogivemybasis forsome concern ononepartandlittleconcern ontheother.
Chairman
822. Thank youverymuch. CanIaskaquestion which actually comes intothefirstquestion, but
itisrelated here. Dothestudies considered byJECFA evaluate carcinogenic effect ofthehormones
atissue? Wasthistaken intoaccount bythestudies which JECFA considered?
Dr.McLean
823. Yes,theywere. JECFA actually looked attrenbolone acetate ontwooccasions because it
requested additional information. Iwillsaythatthecelltransformation assays under somecircumstances
were equivocal, theyweren 'taccepted byallasbeing positive. Ofcourse thecarcinogenicity was
investigated thoroughly andonbalance Ifeelthatthiscompound, thiscompound isbeing pretty much
looked ataswellasanycompound andindeed forsome ofstudies weaskforelectron microscopy
rather thannormal microscopy todetermine certain endpoints. Andofcourse thenoeffect levels
arebased onfairly innocuous changes inmonkeys andtheyareverylow,andthenontopofthatthere
arefurther safety factors forspecies, inter- andintra-species variation. Soyouhavegotthatchain
builtin.
824. IfIcould addjustonething, when wewere talking about theincreased incidence ofbreast
cancer ofone,Ithink, itwasin150,000. That'sIthink, according toyourcalculations, amaximum
ofone.[Yes.] Soitcould beanywhere between essentially zeroandoneandIthink it'simportant
toappreciate thatdifference. Andthatcomes backtothepoint thatmycolleague, Dr.Ritter made
thatwhen wearelooking atriskassessment, because it'samathematical consideration, wehavearange
anditliessomewhere between essentially zeroandone.
Chairman
825. Thank youverymuch. Would youliketotalktothispoint.
Dr.Lucier
826. That'scorrect, between zeroandoneandIshould alsoremember tosaythat,when Isayone,
Iwasjusttrying tomake thepoint toputincomparison withtheother oestrogens. Ihavelooked at
someofthatdata,though withthecelltransformation assays andIdon'tfinditequivocal. It'sassociated
withincreased production ofoncogenes intheSyrian hamster embryo cells, therasandmyconcogenes,WT/DS48/R/CAN
Page387
which areanexpression ofthose critical target genes incarcinogenesis. Andtheresult seems tobe
realone.
Dr.McLean
827. Iwasmaking thepoint thatsome ofthestudies were equivocal andsome arenot.
Chairman
828. I'dliketoleave question 7totheendandmove ontoquestion 8.Wehavethesituation of
abanorprohibition withqualifications andifIamcorrect thatDr.André contended thattheabuse
willoccurinsimilardegreesinsituationswhereonebansthehormonesindisputeasopposedtosituations
where allows thesehormones under certain conditions. Isthereanydataavailable inthisrespect which
could support yourthesis?
Dr.André
829. Theresult, asIsaidyesterday Ithink, inFrance weknew thetwosituations andthesame
hormones wereallowed between 84and89.SoIdon'tknow really ifthedataareavailable. They
areinmyGovernment andofficial bodies andmaybe itispossible togetrealdatainarchive from
thatdate. ButIcanjustgivesome witnesses onthis. Forexample, during theauthorization ofthese
hormones, fiveyears ofauthorization, wefound some positive results, positive results ismisuse, of
theDES. AndtheDESmisuse haddisappeared intheearly seventies. Soitwasacoming backof
DESmisuse during thisperiod. Asecond factisthatithasbeensaid. Ispeak forFrance, notfor
other countries, okay?, thatinFrance, thebanhasbeen followed bythemisuse ofnewclass of
hormones, so-called betaagonist. Andit'sclear thatwediscovered themisuse ofbetaagonist just
aftertheofficial ban.Butinfactwhen now, withthemethods wehave, when welookinfeedsamples
taken during theperiod where thehormones wereauthorized, wefindalsoclenbuterol orbetaagonists.
Somyideaisthattheauthorization, legalization, ofthese compounds hadnoeffect, realeffect on
some black market andthemisuse ofhormones.
830. Thesecond partofyourquestion isconcerned withthecontrol. Andtoknow ifthecontrol
iseasier under regime, withabanornot,Iwould justanswer thatit'sclearly easier technically for
allthexenobiotics. Because ifyouhavenotanyxenobiotics allowed eachtimeyoufindoneit'sclearly
amisuse. Andit'salsotechnically more easybecause youhavejusttohavequalitative survey, Imean,
youhavetocheck inyoursample meat, urine, feeds, whatsoever, youhavejusttolookifthecompound
ispresent. Andthenyousay,yesit'spresent. Soyouhaveaqualitative analysis. When hormones
areallowed, thenit'sthesame thing fordrugs, andsoyouareobliged todoaquantitative analysis,
more complicated analysis tocompare withthetolerance, withtheMRL andsotechnically it'smore
easy. Butit'ssmall differences, anylaboratory know howtodothetwojobs.
Chairman
831. Thank youverymuch. Mynextquestion related tothistoallthePanel members. Isthere
afundamental difference ...[Iamsorry.]
Dr.Arnold
832. Mr.Chairman, Iwould liketoaddfewsentences. Sometimes abanmakes lifeofanalytical
chemists easier. Butnotalways andthereisnoeasyanswer tothatquestion. Igiveyoutwoexamples.
Oestradiol 17-B, isusedasbenzoate illegally andaccording tolegal authorizations fortherapeutic
purposes. Onaroutine basis, theonlywaytodetect thesubstance, currently, istodetect aninjection
site. Although Iknow thatmany people arestarting being abletodetect theester. Butevenifyou
detect theestersomewhere, notattheinjection site,thenit'sstillthequestion, wasitillegal orhasWT/DS48/R/CAN
Page388
itbeenlegally used? Soit'snotsoeasy. Andmostresults havebeenobtained ifpeople hadfound
theinjection siteandiftheywere ablethentogobacktothefarmandlook. Ifsomebody misuses
these substances, thenhenever usesitonanindividual animal basis. Then youtrace backandyou
see,there aremany animals treated thesame wayandthenyouaresure, itwasillegal. So,it'salot
ofeffort andcosts alotofmoney tocontrol this.
Chairman
833. CanIfollow up.Asalayman, Iassume thatifthepractice isillegal andyouwanttoapply
thedrug, youcan'tusetheearmark, because itistooobvious. Sowhatyoudois,youmake massive
injections inthemuscle. Andifwetaketheevidence thatthere hasbeenabout, wasit20,000 cattle
controlled, thisisasmall percentage ofallcattle controlled. Andifyouhappen tobetheconsumer
ofgetting thatmuscle, isn'tthere ariskthatyouhaveenormous intake? Imean, istheriskgreater
under abanthanwhen it'scontrolled? Thisisthemain argument andIwould liketojustaddthis
oneandIhavetwomore elements which should gowithit.Weshould alsoconsider thecontrol of
imports under thetwothings. Andthefinalpoint is,isthere afundamental difference between
controlling hormones thanfrom other veterinary drugs andsubstances used. Does itallow a
fundamentally different approach thanwhatwehaveinother areas?
Dr.Arnold
834. Mr.Chairman, theusefortherapeutic usesisbyinjection. Thisistheonlywaywhich is
permitted. Sotheillegal people, theydoitbyinjection andtrytohidetheinjection site.Soyouhave
injection inboththecases. Thismakes thething sodifficult.
Chairman
835. Butyoucantrace it,because itisusedbytheveterinarian onthetherapeutic side.
Dr.Arnold
836. Youcanaskthefarmer toshow hisprescription, forexample. Soyouhavetodoalotof
effort. Simply byanalytical means it'sverydifficult toanswer thequestion whether ithasbeenused
legally orillegally.
Dr.André
837. Yes,inshort, concerning thecontrol ofhormones andother drugs, Ithink theproblem isthe
same. Because wehavealsotocheck forbanned compounds aschloramphenicol andtheproblem
isthesame tocontrol forchloramphenicol asfortrenbolone ornandrolone. It'snotreally different,
Ithink. Thecontrol ofimported meat, theproblem isthatitisimported meat. Itisnotaliveanimal
andit'sclearalso,everybody, every scientist, analytical mancansaythatit'smore easytowork on
feed,towork onurine, astowork onmeat. Soit'smore difficult. It'snotimpossible. Butit'smore
difficult. Andconcerning yourthirdshort question, theoccasional consumption ofthemeatwithan
injection site.Thisishighly improbable. Because, formany reasons: firstofall,theseinjected solutions
aremainly oilsolutions ofbenzoate, oestradiol andother compounds. Sothebutcher islooking for
whatitis.Heiscutting anditisveryimprobable thataninjection sitecanbeeaten. Even ifitis,
letmeremind youthatitisanoccasional consumption. Itwillnever be,youhavenoopportunity
toeateachdayaninjection site. Itwould beanexceptional thing andmaybe youwillbeinformed
bythenews ofthatverystrange thing.WT/DS48/R/CAN
Page389
Chairman
838. Thenextpointisrelating tothelabelling. Youhadawritten question onlabelling, theanswers
werefairly short inmostcases. Andwewould liketobackuponthisone.There aretwoapproaches.
Youcould havevoluntary labelling basically ofmeatwhich hasnotbeentreated, whatwecallgreen
labels, andyoucanhavemandatory labelling oftreated meat, which hastobeenforced. Reading this
question, doyouthinklabelling would beafeasible approach? Ifnot,inwhatwayswould thislabelling
procedure differ fromthecontrols already carried outbytheECtoensure thatimported meathasnot
beentreated withhormones atall?Isthefactthatonecannot distinguish between treated anduntreated
meatsufficient reason nottolabelmeat? What isthedifference between labelling already carried out
today, evenwithrespect tomeat, suchasthismeatisBSE-free orAmerican meat, orFrench meat,
andlabelling forpurposes astowhether meatisorisnottreated withhormones? Imean thelabelling
isamajor policy today inmaking orleaving decision toconsumers. Most reactions were negative
except yours, Dr.Lucier. Andweneedtoknow littlebitmore whyyouthink thisisnotadoable
way. Now, butwellthat'sananswer yes. Butmaybe, youhavescientific reasons toowhich itis
notdoable.
Dr.McLean
839. Imean, anything ispossible, Mr.Chairman. It'sjustthecost. Butifyoulookattherealities
oflabelling meat, especially when theliveanimal isacommodity, it'sbought andsoldandtraded.
Then whatyoumean byuntreated, ifyoumean never evertreated inthelifetime, thenyougotolook
atthecalf,yougottolookatasitchanges hands, onceortwice itmoves intoafeedlot. Soyouhave
gotachain ofidentification, youreally needapassport witheachanimal, towhich eachowner attests
thathasnever treated andtheirpassport goesonwith...
Chairman
840. Itcould beanother earmark.
Dr.Lucier
841. It'sapractical problem. Theother difficulty iswiththenaturally-occurring substances, how
doyoureally determine whether ithasbeentreated ornot,except forthepresence ofthepellet in
theear.Because analytically youcan'ttellwhether ithasbeentreated. Andthereisanother problem
withzeranol. Insome countries, Fusarium which produces thezeranol-like components contaminates
pasture andfeed. Andthere arecountries intheEC,Ibelieve, where when itcomes totaking the
farmer tocourt forexample, itisimpossible really toprove beyond allreasonable doubts thatparticular
animal didn'ttakeinafairburden ofthezeranol-like substances thathaveleftsome residue. Sothere
arepractical problems across theboard. AndImade thepoint, andIknow thatit'sunrelated butone
hastolookatthecostofthisagainst thebenefit. Andthebenefit islargely psychological, butthe
costisenormous. Andwhen youlookforexample, there'stheexample thatIgavewiththeoutbreaks
ofE.colifoodpoisoning thatisoccurring allaround theworld, where there arehundreds ofpeople
getting illandanumber ofthem dying, onewonders whether oneisbetter tospend thedollar on
rectifying thisproblem thanputting itintosomething thatcanconfers apsychological advantage to
theperson eating themeat. Asimple practical problem.
Chairman
842. Thank you.WT/DS48/R/CAN
Page390
Dr.Lucier
843. Mywritten comment wasprobably anaive oneinmany respects. ButIthink oneought
nevertheless toconsider whether theprimary source caninfactbelabelled. Obviously there isalot
ofspin-off meatproducts thatwillbedeveloped anditwillbeverydifficult totracethose andlabel
eachofthose. ButIthink itneeds tobelooked atastowhether theprimary source canbelabelled
suchasthisanimal hasbeentreated withagrowth promoting agent forthepurpose ofgrowth promotion.
Ithink itcould benarrowed down tothatandperhaps benotquitesocostly asiffull-blown labelling
procedures were putintoeffect. Ithink ifthat'sallpossible anditisnotgoing tobreak thebank,
Ithink itreally needs tobeconsidered. Imean, afterallifthepublic isconcerned about these issues,
thepublic hasarighttoknow, ifatallpossible.
Chairman
844. Thank youverymuch.
Dr.Ritter
845. Intrying toprepare awritten response tothis,Mr.Chairman, infactIcitedinanumber of
references whounderstand thistopic much better thanI.ButIsuppose thequestion thatIaskmyself
iswhatwould betheobjective ofthelabelling. Because Ithink thathelps todefine thestrategy. We're
accustomed around theworld tolabelling products where aninformed decision isauseful thing to
offer. Ifyouwant tosmoke, these arethepotential consequences. Orthere aremany therapeutic
drugs, notnecessarily veterinary medicines, buthuman medicine, which mayraisetheriskofbirth
defects, andwelabelthem, because theymayconfer enormous benefits topatients. ButIwasunclear
when thequestion wasraised. Toturnitaround, ifitweretheviewofthePanel thattheuseofthese
agents doesnotconstitute ariskthathastobedealtwith, thenIaskmyself what'stheobjective.
Chairman
846. Well, Iamrecalling asubmission which wasintheEC'ssubmission tohighUSGovernment
officials explaining thehormone treatment andwhen hewasasked privately whattypeofmeatdoyou
prefer, hesaid,ifIcanafford itIbuynon-hormone treated beef. AndIthink that'sthesortofchoice
people would wanttomake. Ithink wemake these choices every time, particularly nowattheage
ofBSE. Youfindonthecardinarestaurant, USbeef,beefimported fromtheUnited States andthat's
another label, andthat'salabelinthemeatsector, andsothatlabelsomehow works, Ihopeitdoes.
Dr.Ritter
847. Well, then, Iwould beinclined tothink, ifthat'sthecasetoprovide those whowishtomake
achoice, theopportunity tomake one. Andifit'snotamatter ofhelping aconsumer decide onthe
basis of....[cassette ended.]
848. Ithink ofsome ofthesupermarkets particularly intheUnited States, South West inCalifornia
where therehasbeenawhole culture offranchises that'sdeveloped around assuring theconsumer that
it'spesticide freeorthisresidue free,andmyviewonthatisallpower tothem, ifyoucancreate a
market niche foryourself byoffering aconsumer something which theywantbutwhich maynotprovide
anydirect benefit. ButIunderstood thequestion toasked inthecontext ofaregulatory imposition,
andinthatcontext Iasked myself what'stheobjective. Because ifitdoesn 'thelptheconsumer make
an"informed" decision, andIusetheword informed toimply nottheknowledge thathasbeentreated,
butrather information which canmaterially affect thedecision, thenIhavetoaskmyself ifonecan
justify thecostandeverything elsethatgoeswithitwhen onecould simply allow themarket-place
toaccommodate it.Idon'thavethatviewifit'saquestion ofrisk,ifwe'retalking about adrugthat
mayinduce abirthdefect andaphysician hastomake adecision onbehalf ofhispatient, thanIthinkWT/DS48/R/CAN
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labelling isveryappropriate. Veryappropriate fortobacco, although Ihaveother views about tobacco.
Ithink there isamore appropriate waytodealwithtobacco thanlabelling. SoI'mnotinanyway
trying tosuggest thatconsumers should notbegiven thechoice. Butifthechoice asIsayisbased
onpreference andnotscience, thenmyposition would bethatIletthemarket prevail. Andweknow
fromworldwide experience, IcitetheUSasanexample butthere aremany others, thatindeed there
willbeentrepreneurs whowillgrow uptofillthatniche. AndIthink thatiftheycandothatandtake
advantage ofthatsortofasituation, itisthehallmark offreeenterprise.
Chairman
849. Thank youverymuch. I'mtrying towrap up,there isonequestion Istillhavetoaddress,
atechnical one. Theexperts havenotaddressed (thisisNo.10). Theexperts havenotaddressed
thehormone MGA. Hasanyriskassessment beencarried outwithrespect tothishormone? Does
thishormoneposedifferenthealthriskthantheothertwosynthetichormones?Doyouhaveanyevidence
onthis? It'squestion 10hereonthepaper, thelastquestion.
Dr.McLean
850. Iguess allIcansayMr.Chairman isthatIhavenothadtheopportunity tolookatapackage
ofdata,contemporary data,thatiscomplete, andsotherefore I'munable tocomment andImade that
comment atthebeginning.
Dr.André
851. Justacomment, onemajor riskforthese hormones istheriskassociated withmanagement
ofanhormone, anactive hormone imported directly inthefeedonthefarm. That'sarealriskIthink.
Inthishormone isverydifferent from theothers, butnomore comment onthis.
Dr.Lucier
852. WellI'mnotsaddled withthesame amount ofinformation mycolleagues aresoit'sdifficult
formetomake acomment because oflackofinformation. There issome, there isareport thatit
produces anequivocal increase inmammary tumours, along-term study andthatit'saverypotent
progestational agent. Theinformation thatIcould getisthatit'sabout 30times more potent than
progesterone andorally active soit'sanextraordinarily potent progestant. Sothatraises some concerns
toxicology justforthatreason. ButIhaven 'tseenthetoxicology studies thatapparently areavailable
butIwould havesome concern based onthese twopieces ofinformation.
Chairman
853. Would itbepossible togetthisinformation forthePanel oristhistoodifficult?
Dr.Ritter
854. No,buttheissue Mr.Chairman, isthatinthecaseoffiveofthesix,Ithink theviewthat
you'veheard fromallofusparticipating, notnecessarily agreeing, butthattherehasbeenasubstantial
amount ofinformation onwhich wehavebased ouropinion. Inanumber ofcases wehavearrived
atdifferent opinions, butwehaveallagreed thatthere hasbeenasubstantial amount ofinformation.
InthecaseofMGA because ithasnotbeensubjected toaninternational review thusfar,aJECFA
review, andbecause information submitted insupport ofthese sortsofpetitions tonational regulatory
authorities isgenerally proprietary, Ithink noneofuswould havehadthebenefit ofthedepth ofthe
review thatwould beavailable fortheotherfive.SoIthinkthatthecautionary notethatyouarehearing,
atleastfromDr.Arnold, Professor McLean andmyself, isthatthemostaccurate thing wecould say
isthatwesimply don'tknow. Imean thatnotonewayortheother butthatIonmyown, would notWT/DS48/R/CAN
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venture aguess onewayortheother because Ihavenotseenonepercentoftheinformation onMGA
thatI'vebeenabletoexamine fortheothers.
Chairman
855. Thank youverymuch. I'dliketocome tothefinaltourdetableonthesideoftheexperts
andI'dliketolinkthistoquestion seven here, Ithink thatthiswillbeatheart ofthe,alsoofthelegal
issues tobediscussed inthiscase. Dr.Liehr hasprovided touswhatiscalled thenewevidence on
thepotential genotoxicity ofthehormones. Other experts havequestioned therelevance ofthisevidence.
Iwould liketohaveyourpersonal views onwhatistherelevance ofthisnewevidence forveterinary
drugs otherthanthehormones atissue, suchascarbadox, andfortheuseofnatural hormones, especially
oestrogens, fortherapeutical purposes. Ifthisnewevidence would beareason tobanhormones added
forgrowth promotion, would italsobeareason tobanallother usesofthesehormones ortobanother
veterinary drugs? Andperhaps before youaddress this,wearenotveryclearonthePanel onyour
fundamental views towhatextent oneshould, ascientist should orshould notconsider when heconsider
theriskforhormone residues, towhatextent heshould really takeintoaccount thegenotoxic effects.
There seems tobedifferent, slightly different views. Butifyoucould stateagain yourposition on
thegenotoxic effects andthenperhaps follow thisup.Howwould youadvise thePanel totakeinto
account thisnewevidence which hasbeenpresented particularly yesterday tous.Maybe we'llstart
withDr.Ritter andthengothrough thePanel.
Dr.Ritter
856. Justveryquickly, Iwon'ttakemuch timeMr.Chairman. Ithink, I'mreminded thatDr.Liehr
mayhavecaptured thereference point onthisinformation thathepresented better perhaps thananyone
else. When hesuggested himself yesterday, Ithink quitecorrectly, thatinorder toestablish thedirect
relevance ofhispreliminary findings, hewasseeking additional research funding. Ithink hesaidthat
theparties tothedispute would havemade abetter investment, iftheywould havefunded himtoexamine
therelevance ofthese findings atthelowlevels which arebeing present, thantheyhaveexpended in
coming tothishearing. Iamparaphrasing alittlebit,butIthink thatwasthegistofhiscomments.
Ithink hehasputitbetter thananyone else. Ithink thefindings areinteresting buthehimself Ithink
hassuggested thattheyarenotintheform orofthenature where theycanbedirectly applicable to
thenature ofthedeliberations here. Thenature ofscientific investigation isthatitgoesforward. And
ifweweretomeetagain inayear, Idaresayyouwould belooking atevidence which youdidn'thave
available today. Imentioned toyouyesterday Mr.Chairman, thatIknow ofnoscientist whohas
eversaidonanyissue, because wearealllooking forfunding, Iknow enough, please don'tprovide
anymore money onthisissue. Iknow I'venever doneit.SoIthink justveryquickly inthecontext
oftherelevance, thatwould bemyview, it'sinteresting, butIlikethewayDr.Liehr phrased it.
857. Interms oftherelevance inalarger sphere toother veterinary drugs, again Ithink theonly
waytoanswer thatquestion istoapply thesame technology toother drugs. Itisconceivable thatif
oneapplied thenewmethodology thatweheard described yesterday toarange ofother veterinary
drugs, pesticides, other foodcontaminants, thatitmight raisetheverysame degree ofconcern that
itseems tohavegenerated inthisdebate overthelastcouple ofdays. Idon'tknow theanswer because
ithasn'tbeendone. Butifyou'dliketoprovide thefunding Mr.Chairman ....Andfinally Ithink
ontheissue ofcarbadox specifically, ifIreadthistobethethirdissue ifyoulike,Ithink inthecase
ofcarbadox there isalready general agreement thatitisagenotoxic agent, sotosubject thatspecific
example tofurther investigation, Ithink would contribute littletoourknowledge because wehave
already concluded thatitiscapable ofthistypeofaction. Subjected tofurther studies would only
confirm whatwehavealready allagreed on.SoI'mnotlooking formore funding onthatone.
Chairman
858. Thank youverymuch. Professor McLean.WT/DS48/R/CAN
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Dr.McLean
859. YesMr.Chairman, thewaythatIreaditwasthatDr.Liehr wasputting forward aninteresting,
along withanumber ofother people, werelooking atthemechanism ofcarcinogenesis ifIcould put
itthatwayandtherefore genotoxicity wasimportant. Thathehadahypothesis, hehadmade aseries
ofobservations andhewastesting thathypothesis andthatmayormaynotbesignificant, when it's
finally worked itswaythrough, tothisparticular group ofhormones. Dr.Arnold didpoint outthat
therewereother hypothesis being tested withsimilar sorts, atthisstage, ofstrength, ifyoulike. And
sotherefore Ithink inrelation tothenewevidence, thejuryisreally stilloutanduntilthehypothesis
firms up,ifIcould putitthatway,thenthere islittlewecando.Anditwould beunfortunate ifthe
hypothesis didn'tstand upandotherhypothesis came forward andweretested andshown tobeeffective
iftheydothatwe'dmade amistake there. Inrelation toother veterinary drugs, many ofthem are
carcinogenic inanimals. Justtoname afew,dimetridazole, metronidazole which iswidely usedin
humans isquite carcinogenic inanimals, yetitisstillused, thesulphonamides arequite carcinogenic
inrodent carcinogenicity tests, carbadox, weknow iscarcinogenic andthat'stoname four. Andto
gothatnextstep,wedon'thavethemechanism oftoxicity inallofthecases. Andwecould develop
ahypothesis andtestitandthenwemight arrive attheprecise mechanism. SoIthinkwehaveasimilar
situation withother veterinary drugs although, withthehormones, theydohaveaveryserious human
health effect inproducing forexample breast cancer andsowe'reputting alotofmoney inthearea
towork thatthrough. Because itisanimportant human health activity andIwould support continuing
research withtheother drugs, theydon'tassume thatimportance andsowedon'tputthemoney in.
Chairman
860. Thank youverymuch. Dr.Arnold
Dr.Arnold
861. Idon'twanttoaddverymuch because Ilargely agree withthetwoprevious speakers. But
should ithappen that,forexample, oestradiol would beidentified asgenotoxic carcinogenic andshould
thisthencause abanofthissubstances forgrowth promotion, Iwould sayfrom theviewpoint ofa
consumer, Icould thennotunderstand itsuseforzootechnical purposes Forexample, thenoneshould
doresearch toreplace thisanduseother substances which could beavailable forthesame purpose.
AndalsoIwould saythenthesubstance should berestricted inveterinary therapy toamore narrow
definition oftherapeutic use. Wehaveaverybroad, asaconsumer, Icannot agree withthisbroad
definition oftherapeutic uses. Anditwould havesevere consequences inhuman medicine because
thenitwould beverydifficult tojustify theuseofthissubstance inoestrogen replacement therapy,
forexample, fortheprevention ortreatment ofosteoporosis where millions ofwomen takeone
microgram, intheorder ofonemicrogram ofmicronized andbio-available amounts ofoestradiol every
day. Soitwould havesevere consequences inmany areas.
Chairman
862. Professor André.
Dr.André
863. Yes,Ithink thatDr.Liehr gives usnewresults inthemode ofaction ofthese oestrogens in
theircarcinogenic effects, butheisnotalone togivethese results. Wehavemany different ways to
understand howtheyact.Thedifference hereisitacomplete theory which seems veryunderstandable
andtherelation between oestrogens andDNA seems tobemore identified thatitwasearlier, forthis
it'sclear. ButIthink thatifweadmit thatthese hormones aregenotoxic, it'stwoverydifferent things
tobanthemasgrowth promoters, asIsaidyesterday, inalargescaleforallpopulations anditisvery
different fortheiruseastotherapeutic use. It'sthesame difference asItriedtoexplain withmyWT/DS48/R/CAN
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example. Astherapeutic use,theyareusedinoneanimal foronetimeandusually forreproduction
purposes, soit'sacompletely different thing. Sotheycanbebanned forgrowth promotion andthey
canbeusedfordrugs. ButIagree withDieter Arnold onthefactthatthere issome problems inthe
definition ofwhatistherapeutic useandalsohowtoevaluate really adrugfortherapeutic use,asis
doneclassically foryears nowbydifferent committees, andtheuseofcompounds forother purposes
thanreally therapeutic use.Andinthiscase, tomyopinion, theevaluation hastobemaybe different.
Chairman
864. Thank youverymuch. Dr.Lucier.
Dr.Lucier
865. Mycomments willbeabitdifferent. Ithink thework thatDr.Liehr isdoing, Ithink it's
important topoint out,ashehas,isthatit'snotjusthimself. There isagroup ofscientists whoare
looking attheroleofoxidative damage andgenotoxicity ofoestrogens, himself andseveral other folks
throughout theworld. AndIthinkthisactivity isveryimportant toourunderstanding ofhowoestrogens
andhowhormones maycause cancer. SoI'mastrong supporter thatkindofwork, Iactually have
acouple ofpublications initmyself. Butforthisnarrow purpose thatwearetalking about today,
about theinfluence ofthisonadditional riskfromoestrogens fromeating, consuming meatcontaining
oestrogens fromgrowth promoted animals, itdoesn 'thavetoomuch consequence. IfIdidacalculation
ofriskasI'vedone, thisoneinamillion thing howthathasbeenmuch discussed, Iwould come up
withthesame calculation whether ornotoestradiol wasgenotoxic. Thatwould bearnoinfluence on
thecarcinogenic riskastheassumption iswearealready onalinear partofthecurve interms ofamount
ofoestrogen, themagnitude ofoestrogen andthemagnitude ofresponse, sayforbreast cancer. Iwould
come upwiththesame answer either case; there would benodifference intherisk. SoIthink in
thatrespect whether ornotoestrogen isgenotoxic, haslessconsequence thenwhat wetalked about
uptothispoint intime.
Chairman
866. Wellthank youverymuch foryourfinalstatements. Thisbrings ustotheendofthisexpert
hearing, Icome toprocedures, which brings ustotheendofthistwo-day meeting. Inmyview, the
combination bothofyourexcellent papers, andIknow youtookpains towrite them inawaythat
thenormal person canreadit,together withyouroralpresentations andthequestions andcomments
ontheparties, Ithink haveexceedingly helped toinform thePanel onthescientific side.Asidewhich
isverydifficult andverycomplicated. Itisalmost ascomplicated astheprocedural one,butnotas
much. Sothank youverymuch foryourtremendous effort andalsotheeffort youputinsuchashort
timetoassist thePanel which isoperating under theseverystrictrules. Thank youalsotothedelegations
forassisting inthese proceedings. Thank youinparticular alsoforthescientists whosatwiththeEC
delegation andcame heretopresent theirviews andtheirconvictions andinform usaswell.
867. Sothisbrings ustothefinalprocedural point. With aviewtothemeeting tomorrow, which
isthesecond substantive meeting, thePanel hasreflected andinthelightofthefactthatthishasbeen
ajointmeeting today andwehaddifficulties tomake decisions about whatisnewevidence, whatis
anewargument, andsoon,andalsoinlightofthefactthatallthepapers havebeenexchanged in
thetwoproceedings, thePanel hastaken adecision tocome backtoitsrightwhich itreserved before
andwedecided toinvite theUnited States delegation toattend themeeting tomorrow. Doyouhave
anyother points onprocedure?
Mr.Brinza (US)
868. Mr.Chairman, youanticipated correctly thequestion Iwasgoing toask,thank youWT/DS48/R/CAN
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Chairman
869. Professor André
Dr.André
870. Justonbehalf ofmycolleague experts, Iwould liketothank youfortheexcellent level of
thisdebate, duemainly toanexcellent chairmanship.
Chairman
871. Thank youverymuch. Sothemeeting isclosed, goodnight. I'msorry, ...Mr.Christoforou,
youwanted thefloor.
Mr.Christoforou (EC)
872. YesMr.Chairman. Iwould alsoliketothank theexperts, anditisnotusual procedure but
wewould appreciate ifitispossible togetthetyped version ofwhatwasdiscussed heretoday. Iknow
itisnotusual, butIthinkitwould beveryuseful ifwecangetthediscussions today typed andcirculated
totheparties.
Chairman
873. Yes,thisisunderway, butitwillofcourse takesome time. Butthiswillbedoneyes.
Mr.Thompson (Canada)
874. Itoowould liketothank again theexperts forparticipating, Iwaswondering whattimewe
arereconvening tomorrow andisitinthisroom.
Chairman
875. Thank youverymuch, themeeting willbea10:00 inthisroom here. Sothemeeting isclosed.