RESTRICTED
WORLD TRADE G/SPS/W/24
4July1995
ORGANIZATION(95-1827)
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
Introduction
1. Theprimary taskoftheNational Food Authority (NFA) istoassess anddevelop foodstandards
andvariations tofoodstandards, fortheprotection ofpublic health andsafety (National FoodAuthority
Act1994).
2. Thispaper summarises howtheAuthority defines, assesses andmanages riskinrelation to
thesetting andvarying offoodstandards inAustralia. Riskassessment andmanagement underlie the
existing regulatory structure andprocedures ingeneral applying inAustralia andthese aredescribed
more fullyinanAuthority 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. Thebroad concept of"risk", however, hasmany dimensions,
andtheprobability ofadverse health effects, asdetermined from ascientific viewpoint, isjustone.
Other dimensions include psychological factors, social andethical factors, andpolitical andeconomicG/SPS/W/24
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factors. Riskassessment, asperformed attheNational Food Authority, isdefined asthescientific
assessment ofriskandisperformed independently ofthese other dimensions ofrisk,although they
maycontribute tothesubsequent 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(safety)
orlongterm (public health). Thetwoterms, "public health" and"safety" aresometimes used
interchangeably because oftheirclose relationship buteachhavecharacteristics which differentiate
them.
9. ForagriculturalandveterinarychemicalsregulationinAustralia,maximumresiduelimits(MRLs)
areenforced byStateandTerritory authorities according totheAustralian FoodStandards Code. MRLs
areestablished largely byother agencies, namely, theNational Registration Authority forAgricultural
andVeterinary Chemicals (NRA) andtheDepartment ofHuman Services andHealth.
Steps inriskassessment
10. Theprocess ofriskassessment canbedivided intofourdistinct steps, namely, hazard
identification, hazard characterization, exposure assessment, andriskcharacterization. Thevarious
steps inthescientific assessment ofriskareconsidered below. Because chemicals infoodconstitute
amuch larger anddiverse group ofpotentially hazardous substances thanthemicrobiological hazards
(although notnecessarily agreater risk), much oftheriskassessment methodology hasbeenformulated
around theriskassociated withchemicals.
Hazard Identification
11. 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.
Fornewchemicals, thisisestablished through aconsideration of:(i)thestructure andassociated
physicochemical properties; (ii)themetabolism andtoxicokinetics ofthesubstance; and(iii)the
results ofaseries oftoxicity testsconducted bothinanimal models andininvitrosystems. Theextent
ofthetoxicity testsrequired isdetermined onacase-by-case basis, andwillbedependent onthenature
ofthesubstance andtheanticipated levelofhuman exposure. Animal toxicity studies aredesigned
toinvestigate themajor biological systems andwould cover acute toxicity, reproductive toxicity,
genotoxicity,embryotoxicity,teratogenicity,carcinogenicity,organtoxicity,andsometimesotherspecific
studies suchasneurotoxicity orimmunotoxicity.G/SPS/W/24
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12. 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
13. 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
14. 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
toasdietary modelling. When survey dataisavailable, moreaccurate exposure evaluations forspecified
population groups canbemade. Ingeneral, exposure estimates arebased onknown oranticipated
dietary information forparticular foods together withanestimate ofthelevelofthechemical inparticular
commodities.
RiskCharacterization
15. 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.
16. Forchemicals, riskcharacterization might beexpressed interms ofamargin ofsafety between
theacceptable levelofintake ofanadditive orcontaminant, based ontheknown hazard, andtheknown
levelofhuman exposure viathediet.
17. Themostprohibitive approach toanunacceptable riskistotalrestriction ofuse(forachemical)
oracontamination levelofzero(forachemical orpathogenic organism). Thisapproach maybetaken
for(i)chemicals orpathogens which should notenter thefoodsupply; (ii)chemicals forwhich there
isnotoxicity information; (iii)forcertain agricultural chemicals which arenolonger inuse; and
(iv)certain botanicals which arenotconsidered suitable foruseinfood.
18. Themost common approach withchemicals isthatthepermissible upper level infoodis
controlled through theFood Standards Code. Thus, foodadditives arecontrolled onthebasis ofthe
acceptable daily intake (ADI) andtechnological justification, processing aidsarecontrolled largely
onthebasisofgoodmanufacturing practice (GMP), agricultural chemicals arecontrolled onthebasis
oftheADIandgoodagricultural practices (GAP), contaminants arecontrolled onthebasisofatolerable
intake together withbestmanagement practices.G/SPS/W/24
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19. Whether thepresence ofchemicals, nutrients ormicro-organisms isrestricted ornot,surveys
canbeauseful toolformonitoring actual levels infood. Suchinformation canthenbeusedinestimating
thelevelofdietary intake ofchemicals andnutrients fordifferent population sub-groups, ortheadequacy
ofexisting microbiological standards andCodes ofPractice inminimizing thelevelofpathogens in
foods. Thisinformation isimportant inproviding reassurance tothepublic regarding thesafety and
adequacy ofthefoodsupply.
20. 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 atsafelevels
ofintake forhumans. Thesafety factor (or"uncertainty factor") usedmayvaryfrom 10to2000
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.
21. 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 arenon-genotoxic cangenerally beregulated inasimilar manner toother chemicals
withtheestablishment ofaNOEL andanADI.
22. Environmental contaminants cannot beregarded inthesame wayasfoodadditives since they
arenotintentionally added tofoodandthelevels cannot necessarily becontrolled toprovide thesame
margin ofsafety which canbeachieved withafoodadditive. Thus, assessments must bedone on
thebasisofthelowest achievable level. Maximum permissible concentration (MPCs) areestablished
generally onthebasisofthelowest achievable levels ofcontamination which isconsistent withprotection
ofpublic health andsafety.
Determination oftheADI
23. 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
24. 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 totheADIthanonewhich
caused aslight liverweight increase.G/SPS/W/24
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Useofsafety factors
25. 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
26. 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
27. Uncertaintyinthemeasurementofdietaryexposuretochemicalscanbeduetolackofknowledge
inanumber ofareas. Firstly, variable dietary consumption ofparticular foods bydifferent groups
ofthepopulation. Secondly, information onthelevelofthechemical inthedifferent foodcommodities.
Thirdly, information regarding thelevelofabsorption fromthegastrointestinal tractanditsdistribution
inthebody prior toexcretion.
Chemical riskmanagement
28. 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.
29. 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.
30. Unrestricted usemaybesuitable forchemicals ofverylowtoxicity, andforsome chemicals
which havebeenusedtraditionally infoods 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.
31. Surveys, suchastheAustralian Market Basket Survey, areauseful toolformonitoring actual
levels infood, asconsumed. Theobjective ofmonitoring andevaluation activities istoassess the
public health andsafety impact ofindividual foodstandards, andalsotoassess thecumulative impact
offoodstandards,especiallyoveranextendedtimeperiod.ThedevelopmentofindicatorsandguidelinesG/SPS/W/24
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forthemonitoring andevaluation ofthecumulative influence offoodstandards onthefoodsupply
andpossibly onpublic health andsafety isakeyresponsibility oftheAuthority.