RESTRICTED
WORLD TRADE G/SPS/W/24/Rev.1
30October 1995
ORGANIZATION(95-3338)
Original: English Committee onSanitary andPhytosanitary Measures
RISK ASSESSMENT AND MANAGEMENT INSETTING FOOD STANDARDS
FOR ADDITIVES AND CONTAMINANTS INAUSTRALIA
Submission byAustralia totheMeeting of26-27 June 1995
Revision
Introduction
1. Theprimary taskoftheNational Food Authority (NFA) istodevelop foodstandards and
variations tofoodstandards, fortheprotection ofpublic health andsafety (National Food Authority
Act1991).
2. Thispaper summarises howtheAuthority defines, assesses andmanages riskinrelation to
thesetting andvarying offoodstandards inAustralia. Riskassessment andmanagement underlie the
existing regulatory structures andprocedures applying inAustralia andthese aredescribed more fully
inanAuthority paper thatcanbemade available tointerested parties.
3. Amore informed debate about acceptable levels ofriskinrelation tofoodcanonlybeachieved
through agreater awareness ofriskassessment andmanagement practices.
4. Riskassessment andriskmanagement areregarded astwodistinct processes andthevarious
aspects ofeacharediscussed inthisdocument.
5. Forthepurposes ofthispaper, thefollowing definitions areused:
- Hazard istheintrinsic property ofasubstance tocause harm;
- Riskassessment istheprocess ofusing available information toevaluate thehazard
ofasubstance anditspotential tocause adverse health effects atdifferent levels of
exposure;
- Riskmanagement istheprocess ofintegrating riskassessment results withsocial,
economic andpolitical concerns and,afterconsideration ofalternative strategies, of
identifying astrategy tominimize oreliminate theidentified risk.
Concept ofrisk
6. Riskcanbedefined asthepotential fortheoccurrence ofunwanted negative consequences
ofanevent. Inrelation tofood, thisisusually interpreted asthepotential tocause either immediate
orlong-term adverse health effects. Theconcept of"risk", however, hasmany dimensions, andthe
probability ofadverse health effects, asdetermined from ascientific viewpoint, isjustone. OtherG/SPS/W/24/Rev.1
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dimensions include psychological factors, social andethical factors, andpolitical andeconomic factors.
Riskassessment, asperformed attheAuthority, isdefined asthescientific assessment ofriskandis
performed independently ofthese other dimensions ofrisk, although theymaycontribute tothe
subsequent riskmanagement decisions.
7. Fundamental toanestimation ofriskistheacceptance ofadegree ofuncertainty. Thebasis
ofthisuncertainty istwo-fold. Firstly, there isuncertainty withregard tothequantity andquality
oftheinformation upon which adecision ismade. Secondly, there isuncertainty withregard tothe
validity oftheassumptions upon which theprediction ofriskismade, suchasspecies extrapolation,
dietary modelling orthedegree ofheterogeneity inthepopulation. Together, thesedetermine thedegree
ofuncertainty intheriskestimation inaparticular circumstance.
Food-related risks
8. Theprotection ofpublic health andsafety isthemost important ofthefactors taken into
consideration when setting andmaintaining foodstandards. Public health andsafety inrelation tofood
refers toallthose aspects ofthedietwhich could adversely affect human health either intheshort or
longterm. Thetwoterms, "public health" and"safety" aresometimes usedinterchangeably because
oftheircloserelationship buteachhavecharacteristics which differentiate them, suchasthetimeframe
ofaneffect, definition oftheoutcome, andindividual versus population effects.
9. Therisksassociated withfoodareprobably bestconsidered fromthepointofviewofthewhole
diet,although thenumber ofconfounding factors make thisadifficult taskinmost cases. More
commonly, risksareassessed foraspecific foodorforanindividual component ofthatfood. Chemical
factors associated withfood-related risksinclude foodadditives, cooking andprocess-related factors,
environmental contaminants, foodprocessing aids,marine toxins, mycotoxins, novel foodcomponents,
packaging migrants, pesticide residues, plant toxins andveterinary chemical residues.
10. TheAuthority hasaresponsibility withrespect toeachofthese riskfactors. Forsome, such
asfoodadditives, processing aids,andcontaminants, theAuthority hasamajor responsibility toestablish
andmaintain foodstandards where necessary toprotect public health andsafety. Inother areas, such
astherisks associated withnaturally-occurring toxins andother potentially toxic chemicals formed
during cooking andprocessing, foodstandards arenotgenerally considered tobetheappropriate risk
management approach. TheAuthority maywork withother Agencies andorganizations toreduce
therisksthrough encouraging better foodprocessing practices orthrough public education programmes.
11. Foragricultural andveterinary chemicals, while maximum residue levels (MRLs) areenforced
through theFood Standards Code andStateFood legislation, MRLs areestablished largely byother
agencies, namely, theNational Registration Authority forAgricultural andVeterinary Chemicals (NRA)
andtheDepartment ofHuman Services andHealth.
Steps inriskassessment
12. Theprocess ofriskassessment canbedivided intofourdistinct steps, namely, hazard
identification, hazard characterization, exposure assessment, andriskcharacterization. Thevarious
steps inthescientific assessment ofriskareconsidered below.
Hazard Identification
13. Hazard identification isthequalitative evaluation oftheadverse health effects ofasubstance(s)
inanimals orinhumans .Forchemicals, hazard identification establishes thetoxicity ofasubstance
andmayidentify thesetofinherent properties which make itcapable ofcausing anadverse effect.G/SPS/W/24/Rev.1
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Fornewchemicals, thisisestablished through aconsideration of:(i)thestructure andassociated
physiochemical properties; (ii)themetabolism andtoxicokinetics ofthesubstance; and(iii)theresults
ofaseries oftoxicity testsconducted bothinanimal models andininvitrosystems. Theextent of
thetoxicity testsrequired isdetermined onacase-by-case basis, andwillbedependent onthenature
ofthesubstance andtheanticipated levelofhuman exposure. Animal toxicity studies aredesigned
toinvestigate themajor biological systems andwould include acute toxicity, reproductive toxicity,
genotoxicity,embryotoxicity,teratogenicity,carcinogenicity,organtoxicity,andsometimesotherspecific
studies suchasneurotoxicity orimmunotoxicity.
14. Forexisting chemicals, toxicology datamayalsobeavailable frompublished papers although
thequality ofthisdataisvariable. Insome cases, human toxicology datamaybeavailable. Thiscould
include: (i)casestudies ofadverse effects; and(ii)results ofepidemiological studies. Individual
casestudies maynotbythemselves behighly significant, butapattern mayemerge overaperiod of
timewithincreasing numbers ofreports ofadverse effects.
Hazard Characterization
15. Hazard characterization istheprocess ofestimating therelationship between thedoseofa
substance(s) andtheincidence ofanadverse effect.Forchemicals, hazard characterization involves
aconsideration oftheresults obtained inthehazard identification phase inrelation tothedoselevels
used. Theoutcomes should be:(i)identification ofthemajor toxicological endpoints andthedose
levels atwhich theyoccur; (ii)anestimate ofthedoselevelbelow which theobserved toxicity does
notoccur; (iii)some understanding ofthemetabolism andkinetics ofthesubstance inamammalian
system; and(iv)insome cases, information onthemechanism ofaction oftheobserved toxicity.
Exposure Evaluation
16. Exposure evaluation istheevaluation ofthemagnitude andduration ofactual oranticipated
human exposure, andthenumber ofpersons affected .Forchemicals, exposure evaluation involves
estimating thelevelandextent ofhuman intake ofaparticular substance inthewhole diet. When the
exposure evaluation isbased onestimated oranticipated exposure, theprocess issometimes referred
toasdietarymodelling.Wheresurveydataisavailable,moreaccurateexposureevaluationsforspecified
population groups canbemade. Ingeneral, exposure estimates arebased onknown oranticipated
dietary information forparticular foods together withanestimate ofthelevelofthechemical inparticular
commodities.
RiskCharacterization
17. Riskcharacterization istheprocess ofestimating theprobable incidence ofanadverse health
effect tohumans atvarious exposure levels, including adescription oftheuncertainties involved .Risk
characterization brings together theinformation oftheprevious steps inorder toprovide apractical
estimate ofriskforagiven population. Itisonthebasisofthisdetermination thattheriskmanagement
strategy isformulated. Thedegree ofconfidence inthefinalestimation ofriskwilldepend onthe
uncertainty factors identified inprevious steps.
18. Forchemicals, riskcharacterization might beexpressed interms ofamargin ofsafety between
theacceptable levelofintake ofanadditive orcontaminant, based ontheknown hazard, andtheknown
levelofhuman exposure viathediet.G/SPS/W/24/Rev.1
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General concept ofriskassessment
19. Chemicalriskassessmentdepends,firstly,onanabilitytopredictpotentialadversehealtheffects
inhumans and,secondly, onthefactthatthere isadirect relationship between thelevelofexposure
andtheeffect(s) observed. Theprediction ofpotential adverse effect inhumans generally relies on
evaluation oftoxicity testsinanimals or,inmore limited cases, theresults ofepidemiological studies.
While complete toxicological testing onallchemicals might betheideal, suchanapproach toassessing
hazard isimpractical andindeed unnecessary. Inmany cases, other information isavailable onwhich
toassess potential hazard, including information onthestructure ofthechemical, itsmetabolites, its
rateofmetabolism anditshistory ofuse.Theextent oftoxicity testing which might bedesirable can
generally beestablished afterconsideration ofthese factors.
20. Animalmodelsareselectedonthebasisoftheirsensitivityfortheparticularbiologicalparameter
being measured. Inassessing safety, theconservative assumption ismade thathumans willbeatleast
assensitive asthemostsensitive animal species. Insome circumstances, theanimal model maynot
besuitable ormaybeinappropriate topredict effects inhumans. There isalsoincreasing useofin
vitrosystems tostudy general toxicity andtoexplore mechanisms ofaction. TheAuthority provides
guidance onthetypeoftoxicity studies considered appropriate toassess hazard andtoaddress the
question ofpotential riskinparticular circumstances.
21. Theconceptofadose-responserelationshipisfundamentaltoestablishingthesafetyofchemicals
infood. Animal studies maybeuseful, firstly, toidentify thetarget organs fortoxicity andperhaps
gainsome information onthemechanism ofaction oftheobserved toxicity and,secondly, toestimate
thedoselevel below which theadverse effect doesnotoccur. Thisdoselevel isreferred toasthe
no-observable-effect-level(NOEL).Inordertocompensatefortheuncertaintyinthisfigureasameasure
ofsafety, theNOEL isgenerally adjusted bymeans ofso-called "safety factors" toarrive atasafe
levelofintake forhumans. Thesafety factor (or"uncertainty factor") usedmayvaryfrom10to2000
depending ontheconfidence intheavailable data. Forfoodadditives, asafety factor of100isgenerally
usedwhich comprises afactor of10toaccount forthespecies differences between experimental animals
andhumans, andafactor of10forthevariation inthehuman population. IftheNOEL isbased on
human data,asafety factor of10maybeconsidered adequate, while ontheother hand, iftheNOEL
isbased onlessthanlifetime studies, ahigher safety factor (1000-2000) maybeapplied. Theacceptable
daily intake (ADI) isdetermined byapplying thesafety factor totheNOEL. Forfoodadditives, the
ADIisusedasthebasis forestablishing thesafelevelofhuman lifetime exposure.
22. While thisapproach isapplicable forthemajority ofchemicals which arespecifically added
tofood, there areclasses ofchemicals where adifferent approach maysometimes benecessary. This
includes genotoxic carcinogens, some naturally-occurring chemicals, environmental contaminants,
nutrients andtraditionally-used foodadditives andprocessing aids.
23. Carcinogenic chemicals which arealsogenotoxic present aparticular problem withregard to
safety assessment. Because oftheirability toproduce DNA damage atverylowdoselevels, aNOEL
cannot easily beestablished forsuchchemicals. Ingeneral, theapproach hasbeentodisallow the
useofsuchchemicals infood. When theiroccurrence infoodisunavoidable, either because theyare
naturally-occurringorareproducedduringprocessing,levelsshouldbekepttoaminimum.Carcinogenic
chemicals which arenotgenotoxic cangenerally beregulated inasimilar manner toother chemicals
withtheestablishment ofaNOEL andanADI.
24. Environmental contaminants cannot beregarded inthesame wayasfoodadditives since they
arenotintentionally added tofoodandthelevels cannot necessarily becontrolled toprovide thesame
margin ofsafety which canbeachieved withafoodadditive. Thus, assessments must bedoneonG/SPS/W/24/Rev.1
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thebasis ofthelowest achievable level. Maximum permissible concentrations (MPCs) aregenerally
established onthebasis ofthelowest achievable levels ofcontamination which areconsistent with
protecting public health andsafety.
25. Formany traditionally usedfoodadditives andprocessing aids,thereislittletoxicity dataupon
which tobaseanassessment ofrisk. Many suchchemicals havealonghistory ofuseinfoods orare
members ofchemical classes known tobesafe. Forsome chemical groups, standard toxicity tests
maybeinappropriate toassess hazard. Generally, safelevels ofintake aredetermined using a
combination oftoxicity data,information ontraditional fooduse,structure/activity relationships and
metabolism andtoxicokinetic data.
Sources ofuncertainty
26. Riskassessmentcontainsadegreeofuncertaintywhichisdependentonthequalityofinformation
available andassumptions usedintheassessment process. Factors which mayaffect thedegree of
confidence intheassessment outcome arediscussed below.
Quality ofthetoxicity data
27. Dataquality isasignificant factor inproviding confidence inthedetermination ofhazard.
Poor datacanoften leadtomisleading conclusions which arenotsupported bysubsequent studies.
Quality control measures suchasGood Laboratory Practice (GLP) havecontributed significantly to
improvements indataquality. Insome cases, thissource ofuncertainty istaken intoaccount inthe
choice ofsafety factors usedtodetermine theADI. Formany chemicals found infood, dataisavailable
from various sources andneeds tobeanalyzed critically before conclusions canbedrawn regarding
potential hazard.
Species specificity
28. Thechoice ofanimal model isanimportant consideration ininterpreting toxicity datainrelation
tohuman riskassessment. Insome cases, evenwiththemostappropriate animal model, toxicity studies
canleadtoresults which arespecific tothatspecies only. Recognition ofsuchaneffect cansignificantly
influence theinterpretation ofdataandsubsequent assessment ofrisk. Insome cases, limited testing
inhumans maybedesirable toobtain more relevant toxicity information. Thismight beparticularly
relevant forchemicals ornovel foods which potentially affect bioavailability ofnutrients.
Determination oftheADI
29. Oneofthecriticisms oftheADIapproach isthatthevalue oftheNOEL isdependent onthe
doselevels chosen forthestudy and,insome cases, anoverly conservative ADImayresult. This
uncertainty factor isdifficult tocorrect except byrepeating theexperiment atdifferent doselevels,
butneeds tobeconsidered when questions ofsafety arise forchemicals forwhich theintake is
approaching theADI.
Toxic effect upon which theADIisbased
30. Thenature ofthetoxiceffect uponwhich theADIisbased isimportant when considering the
health implications ofadietary intake above theADI. Thismaybeanimportant consideration when
concern isexpressed regarding excessive intake. Chemicals which cause, forexample, aneurotoxic
effect oraretinal disorder, should bemonitored more closely inrelation totheADIthanthose which
cause aslight liverweight increase.G/SPS/W/24/Rev.1
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Useofsafety factors
31. Safety factors (oruncertainty factors) areonewayofdealing withtheuncertainty arising from,
firstly, species extrapolation oftoxicity studies and,secondly, human heterogeneity withregard to
response tothetoxicity ofchemicals, andaredesigned toprotect themore sensitive members ofthe
population. Ifthetoxicity tohumans isknown, andalsothemost susceptible groups within that
population canbeidentified, thesafety factors canbesmaller.
Dose-response relationships andthresholds
32. Theadvantage oftheADIapproach toestablishing asafelevelofexposure isthatitavoids
extrapolation ofthedose-response curve beyond thedoselevels usedinthestudy. Where nothreshold
doselevelisevident toestablish aNOEL, itmaybenecessary toextrapolate toaso-called virtually
safedoselevel. While mathematical models areavailable toperform suchextrapolations, these are
notconsidered particularly reliable since theythemselves make assumptions regarding theshape of
thedose-response curve. Theonlysituation where itmaybenecessary toconsider extrapolation to
avirtually safedoselevelisforthenaturally-occurring genotoxic chemicals infood.
Measurement ofexposure
33. Uncertaintyinthemeasurementofdietaryexposuretochemicalscanbeduetolackofknowledge
inanumber ofareas; firstly, variable dietary consumption ofparticular foods bydifferent groups
ofthepopulation; secondly, information onthelevelofthechemical inthedifferent foodcommodities;
andthirdly, information regarding thelevel ofabsorption from thegastrointestinal tractandits
distribution inthebody prior toexcretion.
Chemical riskmanagement
34. Thereareanumberofapproachestomanagingtherisksassociatedwiththepresenceofchemicals
infood, including: (i)restricting thelevel ofthechemical infood, ifnecessary; (ii)appropriate
labelling toindicate thepresence ofthechemical and,(iii)aneducation programme tomake thepublic
aware ofpotential risksassociated withexcessive consumption. Thegeneral principle ofminimizing
unnecessary exposure tochemicals underlies eachoftheabove approaches.
35. Themostprohibitive approach toanunacceptable riskistotalrestriction ofuse.Thisapproach
maybetaken for:(i)chemicals which should notenterthefoodsupply, (ii)chemicals forwhich there
isnotoxicity information, (iii)forcertain agricultural chemicals which arenolonger inuse,and(iv)
certain botanicals which arenotconsidered suitable foruseinfood.
36. Themostcommon management approach withchemicals istoestablish apermissible upper
levelinfood. Thebasis onwhich thispermissible levelisestablished willdepend onthenature of
thechemical andthetypeoffoodinwhich itoccurs, asdiscussed below. Labelling offoodisused
toidentify thepresence offoodadditives andmayalsobeusedtohighlight thepotential foradverse
reactions toparticular foods orfoodcomponents.
37. Unrestricted usemaybesuitable forchemicals ofverylowtoxicity, andforsome chemicals
which havebeentraditionally usedinfoods withnoevidence ofadverse health effects. Thisissimilar
totheUS"generally regarded assafe" orGRAS classification. Unrestricted useofachemical may
ormaynotalsoneedtobeaccompanied byapublic education programme. Chemicals forwhich better
understanding oftheriskassociated withtheirconsumption isneeded are:(i)thenaturally-occurring
toxic chemicals infood, e.g.pyrrolizidine alkaloids; and(ii)those potentially hazardous chemicals
which areformed during cooking orfoodprocessing, e.g.heterocyclic amines.G/SPS/W/24/Rev.1
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38. Whether thepresence ofachemical isrestricted ornot,surveys, suchastheAustralian Market
Basket Survey, canbeuseful toolsformonitoring actual levels infood, asconsumed. Suchinformation
canthenbecombined withfoodconsumption dataandusedtoestimate thelevelofdietary intake of
chemicals fordifferent population sub-groups. Thisinformation isimportant toreassure thepublic
regarding thesafety ofthefoodsupply.