Chemistry Reference
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andofthosewhosepatternoffoodconsumptionandphysiologicalorhealthstatusmaymakethem
vulnerable,forexample,“ahighconsumer,”youngage,pregnancy,anddiabetes(SCF2001).The
toxicologicaltestingofachemicalintendedforfoodadditiveuseincludesalargenumberofstudies
suchasADMEstudies,short-term(3monthsinrats)andlong-termchronic(2yearsinrats)toxic-
ity, and short-term and
in vitro
testing for genotoxicity (mutagenicity or clastogenicity). Studies
oncarcinogenicity,oftencombinedwithlong-termstudies,aswellasstudiesonreproductiveand
developmentaltoxicity,arealsorequired.Inaddition,special
in vitro
and
in vivo
studiesoneffects
onthenervoussystem,theimmunesystem,andtheendocrinesystem,aswellasonthemechanism
ofaction,maybeneeded.Therelevanceandscopeofanyadditionalstudiestosupportthesafety
ofuseshouldbeconsideredthoroughlybythepetitioner,andthewelfareandthereduction,reine-
ment,replacement(3R)principlewithrespecttotheuseoflaboratoryanimals(Gad1990)shouldbe
keptinmind.Humantolerancestudiesmayalsobeinformative.
14.5 rISK aSSeSSMeNt OF FOOD aDDItIVeS
The safety evaluation of a sweetener prior to the acceptance as a food additive is performed
inthescientiicprocesscalledriskassessment.Riskassessmentisapartofariskanalysis,which
includesriskassessment,riskevaluation,andriskcommunication.
Theriskassessmentofsweetenersasfoodadditivesisperformedinthesamemannerastherisk
assessmentofanyotherchemicalinfood.Itrequiresexpertiseintoxicologyandexposure(intake)
assessment.Riskassessmentresultsinanupperlimitfortheexposuretothecompoundthroughthe
consumptionoffoods,atwhichlevelorbelowthedietaryexposuretothecompoundisnotexpected
tocausehealth-damaging(adverse)effects.
The procedure comprises four steps: hazard identiication, hazard characterization, exposure
assessment,andriskcharacterization(Renwicketal.2003).
14.5.1 hazard Identiication
Hazardidentiicationidentiiesalltheadversehealtheffectsthatthecompoundmayinherently
cause.Forthispurpose,scientiicdatafromexperiencesfromhumanexposures,studiesinlabora-
toryanimals,and
in vitro
assaysareneeded.Ashumandataareseldomavailable,riskassessors
havetorelyonresultsfromanimalstudiesand
in vitro
assays.
14.5.2 hazard Characterization
Hazardcharacterization(alsoreferredtoasdose-responseassessment)estimatestherelation-
shipbetweenthedoseandtheincidenceandseverityofaneffectandleadstotheselectionofthe
pivotaldatasetinwhichthecriticaladverseeffectisidentiied.Subsequently,thisdatasetisused
todescribeandevaluatethedose-responserelationshipforthecriticaleffectofthetestcompound.
If the data demonstrate that the test compound is nongenotoxic, the identiication of a point of
departurefortheestablishmentofahealthbasedreferencevalue,suchastheacceptabledailyintake
(ADI)isperformed.Apointofdeparturecanbeano-observed-adverse-effectlevel(NOAEL)ora
lowestobservedadverseeffectlevel(LOAEL;IPCS1994).
TheNOAELisdeinedas“thehighestconcentrationoramountofasubstance,foundbyexperi-
mentorobservation,whichcausesnodetectableadversealterationofmorphology,functionalcapac-
ity,growth,development,orlifespanofthetargetorganismunderdeinedconditionsofexposure.”
TheLOAELisdeinedas“thelowestconcentrationoramountofasubstance,foundbyexperi-
mentorobservation,whichcausesanadversealterationofmorphology,functionalcapacity,growth,
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