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1、FishLife-CycleTestGuideline8November2002DRAFTPROPOSALFORANEWGUIDELINEFishTwo-generationTestGuidelineINTRODUCTION1.Thisguidelinedescribesatwo-generationtestwithfishthatconsidersreproductivefitnessinparentsandoffspringasanintegratedmeasureoftoxicant.Italsoenablesmeasurementofasuiteofhis
2、tologicalandbiochemicalendpointsthatallowdiagnosticanddefinitiveevaluationofendocrinedisruptingchemicals(EDCs)orothertypesofreproductivetoxicant.Thisguidelineisintendedtobeapplicabletothefatheadminnow(Pimephalespromelas),medaka(Oryziaslatipes),sheepsheadminnow(Cyprinodonvariegatus)and
3、zebrafish(Daniorerio).Thefishtwo-generationtestisarelativelylong-term(normally180-dorlonger)assaythatassessesearlydevelopment,growth,andreproduction.Thetwo-generationtestdescribedinthisguidelinecombineselementsoftherecentlydevelopedshort-termreproductiontest(Ankleyetal.,2001)andlife-c
4、ycletoxicitytestmethodsdevelopedforfatheadminnow(Benoit,1982)andsheepsheadminnow(Hansenetal.,1978).2.Thetestisintendedtoserveasahighertierforcollectingdefinitiveconcentration-responseinformationonadverseeffectssuitableforuseinecologicalriskassessment.Specifically,thedesignenablestheco
5、llectionofbothmechanism-specifictoxicitydataandinformationconcerningfecundityandviability.Theformerisusefulasabasisfordiagnosisand/orextrapolationacrossspecies,whilethelatteriscriticaltoapplicationofpopulationmodelstoriskassessmentscenarios.3.Thetwo-generationtestisinitiatedwithmature
6、maleandfemale(Pgeneration)fish,eggsarecollectedandF1embryofertility,development,sexualmaturation,reproductionandF2viabilityarealsoassessed.MeasurementsaremadeofanumberofendpointsinbothPandF1generationsreflectiveofthestatusofthereproductiveendocrinesystem,includingthegonadal-somaticind
7、ex(GSI),gonadalhistologyandplasmaorwholebodyconcentrationsofvitellogenin.Additionally,plasmasexsteroids(17β-estradiol,testosterone,11-ketotestosterone)andthyroidhormones(T3/T4)mayalsobemeasuredifitisconsideredthatadditionalusefulinformationmaybegenerated(Ankleyetal.,2001).PRINCIPLEOFT
8、HETES
