406-Skin Sensitsation

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1、406Adopted:17.07.92OECDGUIDELINEFORTESTINGOFCHEMICALSthAdoptedbytheCouncilon17July1992SkinSensitisationINTRODUCTION1.OECDGuidelinesforTestingofChemicalsareperiodicallyreviewedinlightofscientificprogress.Insuchreviews,specialattentionisgiventopossibleimprovementsinrelation

2、toanimalwelfare.Thisupdatedversionoftheoriginalguideline406,adoptedin1981,istheoutcomeofameetingofOECDexpertsheldinParisinMay1991.2.Currently,quantitativestructure-activityrelationshipsandinvitromodelsarenotyetsufficientlydevelopedtoplayasignificantroleintheassessmentofth

3、eskin-sensitisationpotentialofsubstanceswhichthereforemustcontinuetobebasedoninvivomodels.3.Theguineapighasbeentheanimalofchoiceforpredictivesensitisationtestsforseveraldecades.Twotypesoftestshavebeendeveloped:adjuvanttestsinwhichsensitisationispotentiatedbytheinjectionof

4、FreundsCompleteAdjuvant(FCA),andnon-adjuvanttests.Intheoriginalguideline406,fouradjuvanttestsandthreenon-adjuvanttestswereconsideredtobeacceptable.Inthisupdatedversion,theGuineaPigMaximisationTest(GPMT)ofMagnussonandKligmanwhichusesadjuvant(1)(2)(3)(4)andthenon-adjuvantBu

5、ehlerTest(5)(6)aregivenpreferenceoverothermethodsandtheproceduresarepresentedindetail.Itisrecognised,however,thattheremaybecircumstanceswhereothermethodsmaybeusedtoprovidethenecessaryinformationonsensitisationpotential.4.Theimmunesystemofthemousehasbeeninvestigatedmoreext

6、ensivelythanthatoftheguineapig.Recently,mousemodelsforassessingsensitisationpotentialhavebeendevelopedthatoffertheadvantagesofanendpointwhichismeasuredobjectively,shortdurationandminimalanimaltreatment.Themouseearswellingtest(MEST)andthelocallymphnodeassay(LLNA)appeartobe

7、promising.Bothassayshaveundergonevalidationinseverallaboratories(7)(8)(9)(10)(11)andithasbeenshownthattheyareabletodetectreliablymoderatetostrongsensitisers.TheLLNAortheMESTcanbeusedasafirststageintheassessmentofskinsensitisationpotential.Ifapositiveresultisseenineitheras

8、say,atestsubstancemaybedesignatedasapotentialsensitiser,anditmaynotbenecessarytoconductafurtherg