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ARR26 - 3233 415 M236 - 3235 - Doms TRADESECRET StudyTitle 'H-24890:BacterialReverseMutation Test withan Independent RepeatAssay `TestSubstance: H-24890 Authors ValentinOe. WagnIIeI,r M., S. MichellLe.Klug, B.S. StudyCompletDiaotne 19March 2002 PerforBmiionRgeLlaabnocreatory ~ for 9630MedicalCenterDrive RockviMDl2l0e85,0 E. LduPontde Nemao ndu Comrpas ny DuPontHaskellLaboratory P.O. Box 50, 1090ElktonRoad NewDEa19r 714k -00, 50 `PerformingLaboratory StudyNumber /AAS53CH.5020B0T1.L WorkRequest Number ServiceCode TTT Tae Company Saitized. Does not conTtSaCAiGBnI 'H-24890: Bacterial Reverse Mutation Test with anIndependentRepeat Assay DuPont-8968 STATOE F CM OME PLIN ANT CE StudyNo. AAS3CH.502001.BTL wasconductedincompliancewiththe US. FDAGLP Regulationsaspublishedin21CFR 58,the U.S.EPA GLPStandards40CFR160, and40 CFR 7P9ri2n,ctiphleesUofKGGooLdPLaCboomrpaltioraynPcreacPtriocgeirnaamlmlem,attehreialJaasppaencetssewGitLhPthSetfaonldlaorwidn,ag enxdcetphteioOnsE: CD The identity, strength, purity and composition or other `cbhaereanctdeeritsetircmstiondbeeydfintehettheesttiensgtafancdilciotnyt.rTolhseubcsonttarnoclesshubasvteanncoets havebeencharacterizedasper theCertificatesofAnalysis on file `withthe testing facility. "dTheesttabileibtyyortfhtemtheesititnengstfaecainldidtyc.ontrol substances has not been Analyses to determine the uniformity (as applicable), or concentrationofthetestandcontrolmixtureswerenotperformed bythetestingfacility. The Sponsorhasindicatedthattheyhave - `not performedtheseanalysesonthetestsubstancemixtures. Thestabilityofthe testand control substancesinthe testand tceosnttinrgoflamciixltiutrye.sT,hreesSpepcotnisveolryh,haasisnndoictabteeednthdeattetrhmeiynhedabvyentohte `performedstabilityanalysisonthetestsubstancemixtures. Nt ic 0.Weer ValeO.aWt agniern,IeI, MS. `StudyDirector ret x BoSadyo Mamgel ment e 9Mar2003 Date 19 Max 2002 Dw StBiuodRyelNioa.ncAe AS3CH.502001BTL 2 Company Sanitized. DoesnocontTSaOAiGnBI - wFi-t2h4a8n90I:ndBeacpteenrdieanltReRveepresaetMAustsaatyion Test 'DuPont-8968 QualityAssurance Statement StudyTile: IHN.2D4E8P9E0:NBDAECNTTERREIPAELARTEAVESRSSAEYMUTATIONASSAYWITHAN `Study Number:AASSCHLS02001BTL . StudyDiesctor: Valeatine 0.Wagner I, MS. SThisie setyU.hSasFbDoAno(eGdoiovbedidLoadCcibnooartposoyetrPirteeaocipfclooearRpergwourcaetsrsispoenbscos(2.b1 CUeosFfiRin.g r,$8)a, toprbdesoUrmrmSsaemB,dpPliAcdnGgrLapPspserop4ae0chC,,PR T4010) heOKOLF punsbspmsOLTSab,mdeO5CD Protocaa tevaSanda OpertingProcedures. * x loving pionds, has posi, ondofQA lees --~ ++ PlhoasspeectOn P1r8o:tDoosco-l0Re-vi1e6w-Dec.01 ToStudyDi 13-Dec-01 ToMgt 16D! 4% PlihspaectOn 13D-nFfeRb0e2o.t13-Feb-02 ToSnadyDir13Feb02ToMgmtO7-Mar02 oo PlhaaspoctOn Dr1a9f-Mtatro-F12il1R9e-pMoarrt02 ToSudyDi 19-Mar-02 ToMint19-Mar02 [ InpetOn 1Te4s.tDec0o)rc-o1n4t-rDoemca0t1erTioeSlatuddmyiDsiesi14oDnec-0lToMgmt 17-Dec01 Plahpaeec| tOn E1n8t:rDioncgpli-e18c-ouDnetcs0)inTooASmteudsypDroigrr1a8mDec-01ToMgmnt 18-Dec01 PlahopaoctOn 0P8-r0p02a-coO4f-u9Jaimni0x2otTurnoeStudyDie04-102ToMgmt04-Jan-02 PlahspeoctOn 0S8o-Jmainn-c0h2a-n0c8-eJiann-t0o2nToStudyDic08-Jan-02 ToMgmtOJ SBtiuodRyelNioa.nceAASICH.5020B0T1L 3 CompanySanitized. Does not contain TSCA CBI - F-24890:BacterialReverse MutationTest `with anIndependentRepeatAssay DuPont-8968 * PhIanspeectOn * PIhnapectOn PIihspeectOn IispoctOn D1i7we- tiadJ ooTcoonna Stroyolmnsiefeis1- 7l-Jan-1 02To7 Mgnt018-0 Jaa2 2S2yJsuesmdsI2n-spe1c3t-ioFnebA2dTmionSitsutdryuiDoinoLf4-eFetbs0b2stTaonMegro es1t4s-yFseb02 E2n8t-eJrainn-g02ls28c-cJaont-s02nTkooSAtmudeysDpireo2g8r-a1m0-02 ToMgnt29-Jea2 06-FebT-oSt0ud2yDi.r0-6Fe0b-062 T-oMFgmet0b6-0Fe2b-2 PIhaaspeoctOn * PlhoasspeectOn Test1do5rco:ntroFl maeteTriobaSl ua0ddymD2iisrs-IiSFoe1nb-052 T-oMgFmte15b-Fe2b-2 S2y0s-eF-Om2bTseors.vSattiy-oLnDoif0cTs1e1-tMSpya:sctee2mMTDooMtcaaCgolril0e1c0-tiMooanr2-a0nn2dlor PlaospeectOn ZS8i-mFienbc0ha2mc-i2e8i-zFaetbi0o2n ToStdyDir2-Feb02 ToMgmt28-Feb02 - ++ ILnssppeecctonsectfortissy Tehfiescretpoorrtdwesdcrtibeosfthteemneyd.sodrocedorsused nthesutyyand herepreosulrtsstureeldy " : ASSURANCE 19 Mon2002 ATE BSitouRdeylNiow.cAeAS3CH.502001.BTL 4 `CompanySaniized. DoesnotcontTSaCAiCnBI 'H-24890: Bacterial Reverse Mutation Test with an Independent Repeat Assay DuPont-8968 CERTIFICATION `We,theundersigned,declarethatthisreportprovidesanaccurateevaluation ofdataobtained from this study. sodbyStudyDincor__ NaluaEiia ogo, Valentine O. Wagner IIL, M.S. 19 Mar 2652 Date. sApproy ved by Mo Dene SeoReve Sees Maria Donner, Ph.D. boson Date _ StBiuodRyelNioa.nceAAS3CH.502001.BTL 5 GomppmySantas, DoesnotTIEAGS! - 'H-24890: Bacterial Reverse Mutation Test with an Independent Repeat Assay `TABLE OF CONTENTS DuPont-8968 Page BAPnmmmmsmmmmmmmmmm--------------.ly J TC LI RAE sssmmmmmmmmmmm------------------ 1 BRATS ccsnssrmssmmmmmmmmmmmm---------- `TTaabbllee 21:: PPrreelliimmiinnaarryyTTooxxiicciittyyTTeesstt iibn SSaallmmoonneellllaa ttyypphhiimmuurriiuumm TTAAIS0B0...." ......2 ...ov.0 ver19 ~ `Table 3: PreliminaryToxicityTest in Salmonella typhimurium TAIS3S ..._._.__2.1 `Table 4: Preliminary Toxicity Test in Salmonella typhimurium TAIS3T ..........o.o2o2n `Table 5: Preliminary Toxicity Test in Escherichia coli WP2 uVTA.........ooowoon 23 TTaabbllee 76:: MMuuttaaggeenniicciittyy TTeesstt iinn SSaallmmoonneellllaa ttyypphhiimmuurriiuumm TTAA9988 WWiitthhoSu9t S.9...............................2245 `Table 8: Table 9: MMuuttaaggeenniicciittyy TTeesstt iinn SSaallmmoonneellllaa ttyypphhiimmuurriiuumm TTAALIO0Q0 WWiitthhoSu9t..S.9..........................22]6 `Table Table 10: 11: Mutagenicity Mutagenicity Test Test in in Salmonella Salmonella typhimurium typhimurium TALS35 TAIS3S Without S9 ...........28 With S9...............29 `Table Table 12: 13: Mutagenicity Mutagenicity Testin Test in Salmonellatyphimurium Salmonella typhimurium TA1S37 TAIS3 without S9 ............30 With S9.............31 TTaabbllee 1154::MMuuttaaggeenaiicciittyy TTeesstt iinn EEsscchheerriicchhiiaa ccoollii WWPP2 i4orrA WWiitthhoSu9t.S.9.................................3332 TTaabbllee 1167::MMuuttaaggeenniicciittyy TTeesstt iinn SSaallmmoonneellllaa ttyypphhiimmuurriiuumm TTAAIB8 WWiitthho$u9t S.9...........................3354 TTaabbllee 1198::MMuuttaaggeenniicciittyy TTeesstt iinn SSaallmmoonneellllaa ttyypphhiimmuurriiuumm TTAA1L0000 WWiitthho9ut .S9............o.o.o.....o.....3376 TTaabbllee2201::MMuuttagaegneicniitcyTiTeetssytt iinn SSaallmmoonneellllaa ttyypphhiimmuurriiuumm TTAA1I5S3355 WWiitthho$u9t S..9........o.c.o.r.........3398 `TTaabbllee 2223:: MMuuttaaggeenniicciittyy TTeesstt iinn SSaallmmoonneellllaa ttyypphhiimmuurriiuumm TTAALLSS337 Wwiitthho9ut S.9.............4410 BioReliance Study No. AAS3CH.502001.BTL 6 Company Sanitized. Does not contain TSCA CBI - 'wHi-t2h4a8n90I:nBdaecpteenrdiealntRReevpeeraste MAustsaatyion Test DuPont8968 Table 24: Mutageaicity Test in Escherichia coli WP2 wr Without S9..........ov.r2 Table 25; Mutageaicity Test in Escherichia coli WP2 wr With S9.............4o3 Table 26: Salmonella/E. coli Mutagenicity Test ~ Summary of Results BI...............44 Table 27: Salmonella/E. coli Mutagenicity Test- Summary of RESults B2...............45 AppendiAx: BIStORCAlCOMED! Dlr:46 ADPEDBX:SUAY PIOOCOL..rarnn menses 48 `Appendix C: Information for Japanese REGUIBOrY AEDCIES........vvvvvvnorersns 60 BSitouRdeylNioa.nceAAS3CH.502001.BTL 7 Company Sanitized. Does not contain TSCA CBI - 'H-24890: Bacterial Reverse Mutation Test with an Independent Repeat Assay DuPont-8968 STUDY INFORMATION -- HaskellNumber: 24890 Soon: WindiunPgoosntdDeetNvewmoaunr5s6C5o0mpany USA. `IStnuidtyisted/Completed: December 17, 2001 / (seereportcoverpage) IIn-nLiitfieated/Completed: December 19, 2001 / January 24, 2002 BioRelianee Study No. AAS3CH.502001. BTL 8 - wHi-t2h48a9n0I:ndBaecpteenrdiealntReRveepresaet MAustsaatyion Test DuPont-8968 SUMMARY IndeTphenedteenstt RseubpsetaatnAcses,aHy-u2s4i8n9g0S,alwmaosnteelsleadbipnhtihmeurBiacutmertieaslteRsservseirasse TMuAtSaSt,iToAnIT0eDs,twTiAtLhSa3n5 AraoncdlTorA-LiSn3d7ucaenddrEastclhievreirch$i9a.cTohliet"etseesrtswtarasipneWrFfo2rimoerdAiinnttwhoepphraesseensc,euasinndgabtsheen.cpelaotfe idnocsoer-proarnagteifoonmretthheomdu.tTahgeenfiicristtpyhtaesset,.tThheeprseelciomnidn.aprhytaosxei,ctithyetmeustta,gweaniscuisteydtteosets(tinaibtliiaslhathned independentrepea tests), wasused tevaluatethemutagenicpotentialofthetes substance. `Water wasselected as hesolyeatofchoicebasedonsolubilityofth testsubstance wasIancthhieepvreedluismiinnagryatcooxnicceinttyrtaetsti,onthoefm5a0xmigm/ummLdoasnedteast1e0d0wuaLsp5la0t0i0ngug apelrpliatqeD;oustehoilsdetvoes.les te3s3t1e0d5w0ermeg/6m7l, 10, 33 67,100,333, 667, 1000, 3333ancd5o00n0 cppelenfr.otCmor0n.cea6n7ttroati1i0oomnsfnfros.m _ `Basedonthefindingsofthetoxicitytest, thepmreacxiipimautemdnoosreapplparteecdiianbtlehteoxmiuctiatgyewniacsityobtsesetrwveads. 50ugp0er p0li. testIendtwheemu1ta0rg0en,i3ce3i3ty,te1st0,0,no3p3o3s3itainvedmu5t0a0g0epngihcprleastpe.onNsoepwraecsiopbistaetrev.ewda.Tshoebsdeorsveedl.evNelos rweedruectoibosnesrivnetdhaetb5a0c0k0gruogpunedrlpalwanteswwietrheeosbtseersrtvreadi.nHsoTwAe1v5e3r5,raendducTtiAoLnSsi?niththreevaebrsteanntcceooufntSs9 activationinthe indepernepdeaettnestt. indi"caTtheertehsaut,ltusnodefrtthheeBcaoctnerdiailtRieovfoetrnhsise sMtuutdayt,ioHn-T2e4s8t90wdiitdhnaontcIanudseepeanpdoesnittRievpemeuattaAgsesnaiyc responsein itherthepresenceor absenceofAroclor-inducedratliver S9. SBtiuodReylNioa.nceAASICH.5020B0T1L 9 Company Sanitized. Does not contain TSCA CBI ~~ H:24890: Bacterial Reverse Mutation Test withanIndependent RepeatAssay DuPout-8968 PURPOSE `mea`sTuhreipnugriptsoasbeiolifttythoiissntduudcyerwevaesr0seemvuatlautaitoentshaetsmeulteacgteendilcopcotoefnsteiavleroafltshtreatiensstosfuSbasltmaonnceebllya aynpdhaibmsucrniouemoafnAdraoctltohre-tirnydputcoepdhraatnlliovceur$s9o.fAEsccohpeyroicfhtihaecporloitsoicroaliinsWinPc2luudredaiinnAptpheenprdeisxeBn.ce BactTehrieaslRteuvdeyrwsaeMsuctoantdiuocntTeedstt)o,caodompptleyd wJiutlyh1O9E97C(DpuGbuliidsehleidnFeeb4r7u1ary(G1e9n9e8ti)caTnoxdiwciotlhotghye: IPnhtaermmaatceiuotniaclaClosnffoerrHeunmcaeonnUHsaer(m1o9n9i6saantdio1n997o)f. TechnicalRequirementsof Registr.ationof CHARACTERIZATION OFTE ANDCS ONTT ROL SUBSTANCES Tigned hettehstescuobsdteance,H-24890,wasTrheectievsetdbyBioReliwaansceon 13Dizedecebmybterh2e0Sp0o1nasnodrwaass i should bk 16 April2003wasprovi recelp,te test -~ light. Theaisdentity,strength,pwuraistys,ocroemdpoastirtoioomnotermpoetrhaetrucrhearwaicttehrdiesstiiccsoatnot,dperfoitneecttehdeftreosmt snuobtsrteacnecievheavceobpeyeonfdtehtiesrrmeiponretd.bTyhtehsetaSbpiolnitsyoor.fTthheeteSsptosnusbosrtianndicceahtaesdtbheaetnBdieotReerlmiiannecdebwyotuhled Sponsor. TheSponsorindicatedthat BioReliancewouldnotreceive acopyofthestability report. 713"2T-h1e8v5e)h,iclobetuasiendedtofderloimveIrnvHi-t2r4og8e9n0tCootrhpoertaetsitosny,stfeomrwmearslsyteLriifleediTsetcihllneodlowgaitees,r (ICncA.STNeos.t rsouobmsttanecedmilputieonusrnwdeearreypterleluopwarrleigdehitm.mediatelybeforeuseanddeliveredtothetestsystem at conPtorsolistwiveerceodnitlruotlesdpwliattehddciomnectuhrye]sautllfyowxiitdhet(hDeMmSutOa)geenxicceiptyttseosdtiaurmealzisitdeed,bewlhoiwc.hAwlalspdoisliuttievde with water. All subdividedsolutionsofpositivecontrolwerestoredat-5to ~30C. `BioReliance Study No. AAS3CH.502001.BTL 10 Company Sanitized. Doesnot conTtSaCAiCBnI - wFi-t2h4a89n0I:nBdaecpteenridaelnRteRveepresaetAMustsaatyion Test DuPon-8968 [ome Lon] room |opm| 9 i Concentration Asien -_ J ion Tatas -- fd WrzionriA rm (AuriLcohtCNhoe.mi0c9a1l06CoPsS, Inc) ExpC.ADSatNeo.146-1S3e-p1-328005 Purity 595% (Aldric2hiCthreomfitucoarleCnoe. Inc) ExLp.otDaNtoe. 0O88-7M0ar7-H2S006 `CASPuriNtyo. 650978-%578 (SigSmoadCihoemmiazciadleCo) ExLpo.tDNaot.e 0095-8JHaOn1-629004 CASPuNrioty. 26569298%-2248 Paw-- (LSoitgmNao.Ch1e0m6iFc0a6l6C8o1) ExpC.ADSatsNo1.39-N0o4v5-29004 Purity 598% (A`lMdertihcyhl CmheetmhianccasluClfoo,nsTince) ExpL.oDtaNtoe.218S-N5o2v6-A20003 CAS No. 66.273 muta"gTeonciocniftiyrmtestth wsaesiplltatyeodfotnhesetleetctsiuvbesatagnacrewitthehhainghaelsitqtueosttvsoulbsutmaenecqeudaolseoletvhealtuusseeddiintthhee test.Theseplateswereincubatedunderthesameconditions athetest. BStiuodRyelNaon.ceAAS3CH.S02001BTL u Company Sanitized. Doss not contain TSCA C81 - H-24890:BacterialReverse Mutation Test with an IndependentRepeatAssay DuPont-8968 MATEARNDIMAETLHOSDS Forsubmissionto Japaneserogulatoryagencies,additionalinformationisincludedin AppendiCx. Test System Thetester rainsusedweretheSalmonellatyphimuriumhistidine auxotrophs TASS, TAI00, TAIS35 and TAIS37 as described by Ames ef al. (1975) and Escherichia coli WP2 vr asdescribedbyGreenandMuriel (1976).Salmonellatesterstrainswerereceived directlyfromDr.BruceAmes,UniversityofCalifornia, BerkeleyandE.colitesterstrainswere: receivedfromthe NationalCollectionofIndustrialandMarine Bacteria,Aberdeen, Scotland. Testerstrains TASand TALS37arerevertedfromhistidinedependence (auxotrophy)to histidine independence(prototrophy)byframeshiftmutagens. Testerstrain TALS3 isreverted bymutagensthatcausebasepairsubstitations.Testerstrain TAI00isrevertedbymutageasthat cmaeuchsaenbiostmhifnraEm.ecsohliifitsasnednsbiatsievepatoirbsausbes-tpiatiurtsiuobnsmtiuttuattiiononmsut.aStpieocnisf,icriattyhoerftthhanefrreavmeersshiiofnt `mu(Gtreean atndMiurioel,n197s6). _ Overnightcultureswerepreparedbyinoculatingfromthe appropriatemasterplate or from the appropriatefrozenpermancatstockinto avesselcontaining ~50mLofculturemedium.To assurethatcultureswereharvestedin latelogphase,thelengthofincubation wascontrolled and `monitored.Followinginoculation, cachflaskwasplacedin a estingshakezAincubatoratroom temperature.Theshaker/incubatorwasprogrammedtobeginshakingatapproximately 125 rpm a`tmo3ni7t4o2redCsappepcrtorxoipmhaotteolmyet1r2ichaoluyrfsoberftourrebtidhiteyaanntidciwpaatsehdatrivmeestoefdahtarvaepsetr.cEeanctthrcaunlstmuirtetwanacse `vyiiaeblldeincgouanttitteesrtofoanpnpurtorxiiemntaatgealry1pl0atecse,lalnsdptehremidlaltilaiitseor.nThfielebacuttunalottiptreerssewaetredeidnettheirsrmeipnoerdt.by Metabolic ActivationSystem Aroclor 1254-inducedraliver S9wasusedasthemetabolicactivation system.The S9was preparedfrommaleSprague-Dawleyrats inducedwithasingleintraperitoneal injectionof Ar27o0clCoorrc1o25l4d,e5ru0n0timleuske,d.EiavcehdabuylskpprrieopratroastaicorniofficSe9.Twhaes $e9swteadsfboarticshapbirleiptayrteodmaentdabsotloirzeeda2taminoanthracene and 7,12-dimethylbenz(a)anthracene to forms mutagenic to. Salmonella Dyphimurium TAL00. The $9mix waspreparedimmediatelybeforeitsuseandcontained 10% S9, SmM g3lu3cmoMseK.Cplhiosnphaate1,040mmMMphBo-snipchoattineabmuifdfee-raadetnpinHedi7n.u4c.lTehoetidSehpahmospSh9atmei,xt8umreM(SMhgaCmlm;iaxn)d, `BSitouRdeylNiow.ncAeAS3CH.502001BTL 12 `Company Sanitized. Does not contain TSCA CBI - HW:it2h4a8n90I:ndBeapcetenrdieanltRReevpeerasetAMsustaatyion Test DuPont8968 ccoonnftiarimnitnhge 1s0te0rmilMitypohfotshephSa9taenbudffSehraamtmpiHxe7s.,42,0w.a5mspLrealpiaqrueodtiomfmeadcihawtealsypbleaftoerdeonitssuelseec.tiTvoe agar. SolubilityTest dimetAhsyollusbuillfiotxytiedset(wDaMsScOo)nd,uecttheadntools(eElteOctHt),heavceehtiocnlee.anTdhetteetsrathwyadrscofounrdaunc(tTeHdEu)s.inTghweatteers,t spruebpsatraantcieonwoafsttheeshtiegdhteosdtestoelrubmlienoetrhweorvkeahbilclees,tsoeclkeccotnecdeinntroartdieorno,ufpptreof5e0remngc/e,mtLhaftorpearqmuietoteuds Solvents and500mg/mLfororganicsolveals. PreliminaryToxicity Test subsTthaenpcreewloiumlidnbareytteosxtiecidityntteshte mwuastausgeedntioceitstetsyatb.liVsehhtihceledaosned-treanngdeoosveelrewvehlisochftthheetteesstt substance were plated, one plate per dose, with ovemight culturesof TAS, TAL00, TALS3S, TAIS37 and WP2uvrAonselective minimalagarinthepresenceand absenceof Aroclor-inrdauciveedr $9. Dose levelstestedwere 67, 10, 33, 67, 100, 333, 67, 1000, 3333 and 5000pgplate. = Mutagenicity Test `mut`aTgheen.imcuptoatgeeantiiaclitoyfttehstte(sitnsiuiablstaanncdei.nAdmeipennidmeuntmorefpfeiavtetdeossse)lwevaelssoufsteedsttsoubesvtaalnucaete(t10h0e, 333,1000, 3333and5000 ug/plate)alongwithappropriatevehicleandpositivecontrolswere platedwith TASS, TAIOD, TALS35, TAaIndSWP32u7rinthepresandeabnsencceoef Aroclor-inducedratliver $9. Alldoselevelsoftestsubstance, vehicle conatnrdpoosiltisve `controlswere plated in triplicate. PlatingandScoringProcedures origi`nTahleltyedsetsscyrsitbeemdbwaysAemxepsoeseadlt.o(t1h9e7t5e)astnsduubpstdaantceedvbiyaMthaerpolnaatnedinAcmorepsora(1t9i8o3n)m.ethodology (WIVO)n,twhaesdmaeyltoefdiatsndussuep,pmlienmiemnatletdwoiptahgaLrh,icsotnitdaiinne,iDn-gb0i.o8t%naangdaLr-t(rWy/pVt)opahnadns0ol5ut%ionNtaoCla finalconcentrationofS0iM each.Topagarnotusedwith S9or Sham mixwassupplemented rweiatghe2nt5s,maLllroeffwearetnecrefsor0ewaactheri1m0p0lmyLtoefrem,indiemioanlitzoepdagwaatre.rFporrotdhuecpedbryethpeaMilorlfia-mQetRdeiiaagoaennndt `cWoanttearinSingy15sB%ottt(oWm/eVa)gmaargawr.a. sNuVtrieo ntbog ttomemaignailmrawla-mseVdoBiguelm-EoBo(nVn noegrelmniannide mBaolnnrmere,d1i9u5E6m) BioReliance Study No. AAS3CH.502001.BTL 13 Company Saniized. Does not containTSCA CB wHi:t2h4a89n0I:ndBeapcteenrdiealntRReevpeersaetAMsustaatyion Test DuPont-8968 (cdornytapionwidneg1r)..5N%ut(rWi/enVt)BargoatrhawnadssuVpopgleemle-nBteodnwnsiaetlrht2s.o5lu%ti(onW/sVup)pOlxemoeindteNdutwriitehnt2B.r5o%thN(Wo/.V2) `Oxoid Nutrient Broth No.2 (drypowder). leveEla,ctehsptlearstteawina,slaanbdealcetdiwviattihoanc,aodsedseyssctreimbedtihantiddeetnatiilfiiendtBhiotReesltisaunbcset'asnSctea,ntdeasrtdpOhpaesre,adtionsge Procedures. testOsnueb-shtaalnfc(e0d.i5l)umtiilolinlwiteerroefadSd9eodrtSoh2a.m0mmiLx,of10m0oklLteonftseeslteecrtsitveaitnoapnadg1ar0a0tp4L5o2f2veCh.icAlfetoerr vpolratteixnigtngh,etphoesimtiixvteucroenwtarsoolv,etrhleatiedsotnstuobtshteasnucrefaalcieqoufo2tw5amsLroepflmaicnedibmaylbaotStoOmLaaglairq.uWohteonf appropriatepositivecontrol.Aftertheoverlayhadsolidified,theplateswereinverted and iimnmceudbiataetdelfyorfolalpopwrionxgitmhaetienlcyu4ba8titoon p7e2rbioodurwseraetsto3r7e4d2atC2.-P8laCtuensttihlactolwoenry econuontticnogcunoiueldd becond(esustchant10edayds). toxi"cTihteycboynduistiinognoafdtihsesbeaccttienrgiamlibcarcoksgcroopuen.dPlreacwinpiwtaasteevwaalsueavtaeldfuoarteevdibdyenvciesoufalteesxtasmuibnsattainocne -- wcointthrooultpmaatgenuisfiicnagttihoenc.Toodxeiscisthyoawnndbdeelgorwe.eofprecipitationwerescoredrelative tothevehicle Ce Se [| NSioimghatyl ||DDiusstignugiuisshheeddbbyyaahneoatlitcheyambilcertohcionlnoinnygolafwtnhe._mi_cr_oc_ol_on_yT_a_wa|| 2 Reduced |acnomdpapreod ssibtloytahesvleihgihctlienccornetarsoelipnatteh.esizeofthemicrocolonies Distinguishbeyd amarkedthinning ofthemicrocoloawnny Reduced" |recsomupalretdingitnoatpherovneohuicnlceecdoinnctroelaseinlatet. hesizeofthemicrocolonies| Extremely [rDeissutlitnignugiisnhaednibnycraeanseeixtnrtehmeestizheionnfitnhgoefmitchreocomliocnrioecsocloomnypalrawend] Reduced [1v0tihestveothiihcelbuencaloindteerdoelypelaastiessoulcathetdchoaltotnhieesm.icrocolonylawnis greater thanorequalto 90 oft% he plate. | 6 | ShPrreecuirpeidtabtye|_|Ttho emibcarcokscgorpoicuntdesatscuebsitlanlcoevprecciapimtastbe.ssecurely alate do StBiuodRyelNioa.nceAAS3CH.502001.BTL 14 CompanySanitized. Does not containTSCA CBI H`w-i2t4h8a9n0:InBdaecpteenrdiealatReRveepresaet MAustsaatyion Test DuPont8968 Non-nterfering|[nDaiskteidncguyiesbheudtbaynypprreecciippiittaattee opanrttihcelepsldaetteetctheadtbiystvhiesiabulteotmo attheed| Precipitate |coel.o,nlyecsostunhtear3tnotalparlticles essotnhanapla1t0e%woiftthh3e0rreevveerrttaannttsc)o.lonycount ing [[nDaiskteidngeuyiesahenddbanyypprreecciippiittaatteeopanrttihcelpesldaetteetctheadtibsytvhiseiabulteo1moattehde] PurcerctiepriitnSeg ||cnoolroentyhcaonun3tpearniecxlceseeodn10ap%laotfetwhietrhe3ve0rrteavnetrctoanltosn).yTchoeusnetp(li.e.)s arecounted manuly. conRtreovles,rtwaenrteccooluonntieedsefiotrheargenitviernetleybstyerasuttroamiantaenddcaocltoivnaytcioounnctoenrdoirtienotni,reexloyebpytfhoarndpousnilteisvse theplateexhibitedtoxicity. EvaluoaftReisuoltns plaFteowrecraecchraeplliccateaupnldalatirnaegr,ettphoeretmeedda.nandstandard deviationofthe mumberofrevertantsper - meaFnorretvheertteasntissupbesrtpalnacteetoobfeaetvlaelausatteodnpeotseitsitveer,isttrmaiunsotvcearusaemaidonsiem-uremloatfeditnwcorienacsreeianstihneg p`coosnicteinvteriafttihoenisoncfrteeasstesiunbmsteaanncer.eDvaerttaasnettssafttohrteepsetaekrstorftahinesdToAse1Sre3s5paonnsdeTiAseLqSu3a7lwtoeorrejguredagteerd WtPha2nu3v,r0-Aiwmeesrtehjeumdegaendpvoeshiitcilveeciofntthreolivnaclrueea.sDeiatnamseeatsnfroervetretsatnetrssiartaitnhseTpAe9a8k,oTfAtIh0e0daonsde responsei equaltoorgreaterthan2.0-timesthemeanvehiclecontrolvale. Crifotr aeVarlidiTeast `Sal`mTohneeflollaltoewseitnsgtcrraiitnecruilatmuursestmbuesmtedetmofnosrttrhaetemtuhtaegperensiecnictey oefstttheodbeeepcronosuigdhemruetdavtailoind.(A2l)l atnhedptrheesdeenlceetoiofnitnhethpeKuMvIrOBIgepnlea.sCmuiltduRr-efsacotfort.esAtelrltWraPi2nsuvTrAAcualntdurTeAsm1u0s0mtudesmtodnesmtoruastreatthee: dseploenttiaonneionusthreevuervtraAntgseinnet.hAelvlechuilctlureecsonmturosltsdaesmfonosltlroawtse(tinhcelcuhsairvaec)t:erTiAs9t8ic,m1e0a-n 5n0u;mTbAe1r0o0f, `8n0u-m2be4r0s;oTfAbLaSct3eSr,ia5a-r4e5p;laTteAdL,St3e7s,ter3s-t2r1a;incWuPl2tuurvertAi,ter1s0m-u6s0t.bTeogreenastuerrethtahantoafpepqruoaprliattoe t0h3exn1u0m"bceelrlosf/mreLv.eTrhtaenmiesoavneorfthceamceh paonsitviavleuecoofnttrhoelrmeuspsetcetxihviebviethaitclleeacsotntar3o.l0.-fAolmdiinnciremausmeoifn tohnreeoernobno-tthooxifctdhoesfeollelvoewlinigscrreiqtueirrieadatroeemveatl:ua(t1e)teAs>td5at0a.% Areddouscteiloenvienltishceomnseiadnerneudtmobxeircoiff BioReliance Study No. AAS3CH502001. BTL 1s CompanySaniized. DoesnotcontTSaCAiCnBI - H-24890: Bacterial Reverse Mutation Test withanIndependentRepeat Assay DuPont-8968 r`eavcecstoamnptasnipeedrbpylaatneaabsrcupotmdpoasree-ddetpoetnhdeenmtedarnopvienhtichleerceovnetrrtoalntvcaoluunet..T(h2i)sArtedluecatsitoanmmoudsetrabtee rNeedguacttiivoenianndtPhoesbiatcivkegrCoonutnrdollaVawlnu(ebsaicskignrcoluunddedlaiwnnApcpoedned3i,xA4.or 5).A copyof theHistorical Archives OpeAraltlirngaPwrodcaetdau,rtehOePpQroPt3o0c4ol0bayntdhaelBlioreRpeolritasnwcielRlAbQeAmuaniintthaeiandeqduaarctceorreddiantg: tBoioSRtealinadnacred, 1le4a9s2tt0hBrreoesycehaarrstaRfotaedr,wRhoicckhvtililmee,tMhDe 2S0p8o5n0s.oPrweirlthlbiseScOoPn,tapcatpeedrfroecrora ddsewciilslibonearsettaoitnehdeffoirnaatl dciosppioseidtainondotfhtehceompaytewriilallbs.eArleltsatiundeydimanttehreiaBlisorReetlurinaendcetoatrhcehiSvpeosnfsoorroarmdiensitrmouymedowfi1ll0iysetarbse.: rUensuidsueadltdeosstisnugbssotlauntcieownislwlebreedidsipsopsoesdeodfoffoflollolwoiwnignfgianadlmiiznaitisotnroatfitohnetroetpohrett.estsystem andall Deviations ofthiNsostkundoyw.ndeviationsfrom theprotocolorassay-methodSOPsoccuredduringtheconduct BioReliance - Study No. AASICH.5020B0T1L 16 Company Saniized. DoesnotcontainTSCA CBI - wHi-t2h4a8n90I:ndBeapcetnedrieanltRReevpeersaetAMsustaaytion Test DuPont-8968 RESANUDDILSCUTSSISON Solubility Test i `WaterwasselectedastJ hesolveatofchoicebasedon solubilty ofthetest Preliminary Toxicity Test werTehgeenreersualttesdionftEhxepperreilmiemnitnAalry.ItnotxihceitpyrteelitmairneaprryetosxeinctietyditenstT,atbhleemsa1xtihmrouumgdho5s.eTtheessteeddwaatsa pl5a0t0i0npgaglpiequroptl.aDteo;stehliesvdeolssteewstaesdwacehrieev6e.7d,us10i,n3g3,a6c7o,nc1e0n0t,r3a3t3i,o6no67f,51000m0g,/3m3L3a3anndad5100000ppiLg pceonrcpelnattrea.tiCoonnsfcernotmra0t.i6o7ntsofr1o0mmg/33mtLo 50, were ad precipitantoer a`ppplrateecdiianbtlheteomxicuitytwaasobtgseesretvweadns.5Bi0a0se0cpdoginpetrthpelfyaci. nodftihetnoxgicisty st,themaximumdose. Mutagenicity Test `TabTlhese2r6esaulntds2o7f.tThheemusteadgaentiacwiteyrteegsetnareeraptreedseinntEexdipenrTiambelnetss6Bt1hraonudghB225,aDnodsesluemvmealrsitzeesdtiend `owbesreer1v0e0d,.H3o3w3e,ve10r0,0r,e3d3uc3t3iaonnds 5a0t0h0eruegvpeerrtpanltactoe.unNtosrweedrucetoibosnesrivnetdhaetbSa0ck0g0ruogupnedlcapwlntsewweitrhe teNsotperrtreaicnsiTwpAa1i5so3tb5saaenrtdveTedA.LS37intheabsenceof $9activationintheindependentrepeattest. obseIrnveEdxwpietrhiamnenyotfBthIet(eIsntietirasltrMauitnsaigneeniitchietrythTeepstr)e,sennoceoporsitaibvse.encmeuotfagSe9naicctivraetsipoonn.ses were `obIsenrvEexdpweirtihmaennyotfBt2h(eItnesdteeprsetnrdaiennstiRneiptehearttTheesptr)e,sennocpeoosriatbisveenmcuetoafgeSn9iacctirveastpioonn.ses were CONCLUSION BactAelrlialcrRiteevreirafsoerMuatavtailiodnsTteusdtywwietrheamneItndaespdeensdcernitbReedpienatthAespsraotyoicnodli.caTtheetrhate, sunudoelfrttthhsee pcroensdeinticoenosroafbtsheincsseotdfyA,rHo-c24l8o90rd-idirnnaotdtlciuavecurse$e9d.a positive mutagenic responseineitherthe BioReliance Study No. AAS3CH.502001.BTL 7 `Company Sanitzed. Does not contain TSCA CBI - wHi-t2h48an90I:ndBeapcteenrdieanltRReevpeerasetAMsustaatyion Test DuPont8968 REFERENCES AmesMu,taBgNe,nsJ.wMitchCatnhen aSnadlEno.nYelalmdaMsaamkmial(i1a9n75)MMiectrhosoodmsefoMruDteatgeecntiicnigtyCaTrecsitn,ogMeuntsatainodn Research,31:347-364. GMreaent, MoHnLR.easnedaWr.cJh.3M8u:3r.i3e2l. 1976) Mutagentestingusingtrp reversioninEscherichiacol, InoterfnaPtihoanamlacCeountfiecraesnfoconerHaHrumomnainsatUiseo.n(GIuCiEdDaonfcTeecohnnicSapleRceifqiuciArsempeencttssfoorfRReeggiusltraattoiroyn oGfetnhoeoIrCiHcipyTresotcsofeonrsJPuhlsayrm1a9c,eu1t99i5c.aFlesd.eSra2l4Rdeogcisutmeern6tr1e:c1om8m1e9nd8e-df1oA8rpar2di0ol2p2t4,ion1a99t6.sip 4 IntemoaftPihoanmalacCeonufteiraelnscfeoorn HHoarmmaonnisUaset.ioGne(noItCoHxDiociftyT:ecAhnSictaalnRdeaqrudiBraetmeernytsffoorrGReengoitsotxriactiiotny TpesrtiongcooenfPJshualsryma1c6e,u1t9i9c7alFsedSe2raBldRoecguimsetenrt6re2c:om1m6en0d2ed6fo-Nroa1dvo6epmt0bio3enr021t,s,t1e9p974.ofthe ICH MarMount,atDioMn.RsesnedarBcNh,.A1m13e1s73(2119853.)Revised MethodsfotheSalmonella Mutagenicity Test, `OE1C0DtGhueidOeElCinDeG4u7i1del(GienneestfiocrTtoxhicToelsotgiyn:goBafcCthereimanliRcaelvse,rpsuebMluitsahteidboynTOesE)C,DN,iPnatrhisA,dFdeebnrudaurmy 1998. VogePlr,opHeLrt.iaesn,d1DBMio.l.BConhneemr.(211985:697)-A1c0e6t.ylomithinaseofE. col: arialPurificaandtSioomne BSitouRdeyliNoa.nceAASICH.S02001BTL 18 -- CompanySantized. Dossnot containTSCA CBI H-24890:Bacterial ReverseMutation Test withan Assay DuPout-8968 PBraecltiemriinaalryMTuotxaitciiotnyTeTsetst Table 1 TeSsttudysuNbusmtbaenrce 14: AHN-S2I4C8H5.0502001.87L stExrpaeirniment No. :i AmLss VeDahtieclPelated i: w1a5teDrec 2001 Plating Aliquot : 100 bi TCeosntceSnutbrsattainocne RevWeircthan5t9s ActBiavcaktgiroounnd ug per plate per plate Lown Venicle 18 1 RWeivtehrotuatnts59 AcBtaicvkagrtoiuonnd per plate Lown 2 1 160.1 I1s 11 128 11 3&3 215 11 136 11 130303 867 218 11 1 i 13s 11 5 1 -~ 10330303 23 11 1103 11 5000 16 Background Lawn Code 3 1 i 4i==BNoxrtmraelm;el2y-rSeldiugchetdl;y rS=eAdbusceendt;; JGs=MOobdsercautreeldybyrepdruecceidpitate Np-lon-Interfering precipitate; Ip=Interfering precipitate BioReliance StudyNo. AASICH502001 BTL 19 `CompanySanitized. Doesnot contain TSCA CBI H-24890: Bacterial Reverse Mutation Test with an Independent Repeat Assay DuPont-8968 PBraecltiemriinaalryMuTtoaxtiicointyTeTsestt Table 2 ToSsttudySuNbusmtbaenrce 1d:i HA-A2S4I8C9H0.502001.BTL stErxpaeirninent No. :+ AmL 0 VeDahtieclPelated:t w1a9teDerc 2001 Plating Aliquot : 100 uo CTeosntcensturbasttainocne RevWeirtthan5t9s ActBiavcaktgiroonund ug per plate per plate Lawn Vehicle 159 1 RWeivtehrotuatnt5s9 AcBtaicvkagtrioounnd per plate Lawn 157 1 16.07 116667 11 117667 11 33 116786 11 116586 11 130303 117m3 11 118588 11 - 1056010 116788 11 1m728 11 50330303 115421 11 210708 11 BackgroLeuNnodrmLaalw;n C2o=dSelightly reduced; J=Moderately reduced N4e=sEoxtnr-eImnetleyrfreerdiuncegd;preSc=iApbisteantte;; 6=IOpb=sIcnutreerdfebryinpgrperceicpiiptiattaete BioReliance Study No. AASICH.502001.BTL 20 CompanySanitzed. DoesnotcontTSaCAiCnBI - Hw-i2t4h8a9n0: Bacterial ReversAesMsuataytion Test DuPont. 8968 PBraecltiemriinaalryMuTtoaxticiiotnyTeTsetst Table 3 TeSBsteturdiySnuNbeusnmttbaneNcroe. 1:||: KAAL-A2S4I8G5H0.502001.8TL SDeaetaeinPlated i m15asbese 2001 vePhlaiccilneg aliquot i| w1a0t0er TCugeosntpcoernsturpbalsattciaeonnce RevWeirtthan$t3s per plate ActBiavcaktgiroonund Lave RWeivtehrotuatnt5s9 per place AcBtaicvkagtrioounnd Low Vehicle 1 T Fo) 1 16%7 33 110uw 11 i 11 1 1i i 10&0 333 22s i1 1s 1 2i ii 1 1 - 61000 3333 Fies i i11 270 is ii 1 5000 Background Lawn Code 1 1 1s 3 NTdea-sNBtoxortnnr-aelIn;netley2r-fr5eelrdiuigcnhegtdl;pyrerSceeiAdpbuiscteenadtt;;e;JsT=oPOd-beIsrncatuterereldfyebrryienpdgrupecrceeidcpiiptiattaete -- BioReliance Study No. AASICH.5020B0T1L 2 `Company Sanitized. Does not contain TSCA CBI - 'wHi-t2h4a8n90I:nBdaecpteenrdieanltRReevpeeraste MAustsaatyion Test DuPont-$968 PBraecltiemriinaalryMuTtoaxtiicointyTTeesstt Table 4 STtesutdySNubusmtbanecre 1d:i Boerinent No. | AAHLN-S2I4C8H9.0502001.8TL StvDerantaieicniPelated i i m19asbeyc 2001 water Plating Aliquoe Test Substance 100 4 With 53 Activation Concentration Revertanta Background RWeivtehrotuatnts59 AcBtaicvkagtrioounnd ug pVeebricpllaete' per plate' s Lawn T per plate Lave : b5t.)7 3 5: 5 i3i 255 111 1&00 333 :5 5 11 I 5. ii 1 - 10S6070 3333 83 Ii ` i 57 13 s i e BacSk0gr0o0und Lawn Code e 5 a1 0 7 ai NPLdnzNNEooxnrt-nraTalmn;etley3r-frSeelrdiiugnchegtdl;pyre5rc-eiAdpbuiscteenadtt;;e;J=T-oPOd-beIarncatutereerldfyebryirnepgdrupecrceeidcpiiptiattaete BBoioRkeliance Study No. AAS3CH.502001.BTL 2 CompanySaniized. Doss notconTtSaCAiCnBI 'H-24890: Bacterial Reverse Mutation Test with an t Assay DuPont. 8968 PBraecltiemriinaalryMuTtoaxtiicointyTeTsetst Table 5 TeSsttudSyuNbustmabnecre Id:i HA-A2S4I8C9H0.502001.BTL stExrpaeirniment No. : WAeL2 wma VDeahtieclPelated : w1a9teDrec 2001 BTesR t suUbstC anceELIWiEthY59 m Activam tion sWithout 59 gAectm ivatio-- n Concenxtrapltaitoen ~~ RevertTaanttes BaLckagwrnound Rexverptlaanttes BackLagwrnound Vehicle 5 1 15 1 160.7 1122 11 1186 11 &3 i1s2 11 113 11 130303 1165 11 F1g3 11 - 1056070 117 11 1155 11 53030303 1105 11 1155 11 Backgro1u-NnodrmLaalw;n C2o=dSelightly reduced; J=Moderately reduced N4p=-Etxotnr-eInnetleyrfreerduicnegd;preSc=iApbistenatt;e; GeIOpb=aInctuerrefdebriyngprperceicpiiptiattaete BioReliance StudyNo. AAS3CH.502B0T0L1 2~ `Company Sanitized. Does not contain TSCA CBI H:24890: Bacterial Reverse Mutation Test `withanIndependentRepeatAssay DuPont-8968 Bacterial Mutation Test Table 6 TSetsutdySNuubmsbtearnce Id:: HA-A2S4I8C5H0.S02001.BTL Experiment No i 51 SeLizvaeirnMicrosomes : Naosnse DCealtlesPlSaeetdeedd :: 33.0Jaxn 120002 vePhlaitcilneg Aliquot: w1a0t0erun Concenxtrapltaitoen NPulmabteer Revertlaanttes BacCkogdreound RAevveerratgaents SDteavnidaatridon Vehicle oonz 1155 11 03 w1 1" 2 100 002 i1s 1i 03 15 1 18 1 333 002 118 11 03 01 18 1 ~ 1000 o0r2 1u0 11 03 iz 1 un 1 3333 0021 1220 11 03 16 1 16 ` 5000 0002 11305 111 3 3 Positive Control o2-rnitrofluor1e3n6s 1.0 ug1 per plate 002 1a5n6 11 108 28 BackgroIuenNdormLaalw;n C2o-dSelightly reduced; IsModerately reduced NdP-exltorne-nIenltyerfreedruicnegd;preSc-iApbisteantt;e; GIOPbssIcnutreerdferbiyngprperceicpiiptiattaete BioReliance Study No. AASICH.5020B0TL1 2% Company Sanitized. Does not contain TSCA CBI H-24890: Bacterial Reverse Mutation Test with an t Assay DuPont-8968 Bacterial Mutation Test Table 7 STetsutdySNuubmsbtearnce 1d:: AHA-S2I4C8H9.0502001.BTL Bxperiment No : BL StLirvaeirnMicrosomes : Rmaotsliver 9 CDealtlesPlSaeetdeedd :: 33.0JaXn 210002 VPelahtiincgle Aliquot : w1a00tekrL C1gonpceerntprlaattieon NPulmabteer Rpeevrerptlaanttes BacCkogdreound _RAevveerratgaents SDteavnidaatridon Venicle 0o21 2381 11 0 32 1 30 2 100 o012 a3n6 11 0 18 1 28 5 333 o021 328 11 03 22 1 2 5 = 1000 o02 221 11 03 21 2 2 3333 0021 118 11 03 21 20 3 5000 0012 1280 11 03 15 1 18 3 Positive Control 2-o1anincanthr5a8c9ens 1.01ug per plate 002 1667 1 1 591 125 Backgro1uenNdormLaalw;n C2o-dSelightly dnBxtremely reduced; rSe-dAubcseedn;t; I=eMOobdsecruarteedlybyrepdruecceidpitate NPation-Interfering precipitate; Ip=Interfering precipitate BioReliance StudyNo. AAS3CH.5020B0T1L 2 Company Sanitzed. Doos notcontain TSCA Cal w'Hi-t2h4a89n0I:nBdaecpteenrdiealnRteRveepresaet Mutation Assay Test DuPont-8968 Bacterial Mutation Test Table 8 STetsutdysNuubmsbtearnce strain 1d:+: THAA-A22S04I08C9H0.502001.BTL ECexlplesrimSeenetdeNdo :: 23.19 X 10 VLeihviecrleMicrosones : Nwoanteer Date Plated : 3 Jan 2002 Plating Aliquot : 100 ur uCgonpceerntprlaattieon NPulmabteer pReerveprtlaanttes BackCgodreound RAevveerratgaents DSetvainadtairodn Vehicle 0012 116778 11 0 155 1 160 16 100 0021 116612 11 03 73 1 165 7 333 002 182193 11 0 199 1 200 12 - 1000 0o2 161497 11 03 21 163 1 3333 o012 151647 11 0 rt} 1 155 12 5000 0012 110510 11 03 121 1 125 2 Positive Control soo1dium azide5211.0 ug pe1r plate o0a2 Background Lawn Code 65705 11 sao 0 Nedi==stEoixrotmnra-elIm;netley2r-frSeelrdiuigcnhegtdl;pyreSrc=eiAdpbuiscteeandtt;;e;J=6IN=PoO=dbIeancrtuaertreedfleybrryienpdgrupecrecedicpiiptiattaete BioReliance Study No. AAS3CH.502001.BTL 26 CompanySanitized. Doesnot conTtSaCAiCBnI - Hw-i2t4h8a9n0: Bacterial ReversAesMsutaaytion Test DuPont8968 Bacterial Mutation Test Table 9 TSetsutd.ySNuubmsbtearnce strain 1d:|: + A5A-2S4I8C9H0.SO00L.BTL moo ECexlplesrimSeenetdeNdo :: B2L.9 x 10 LVeihviecrlMeicrosones aRatterliver 59 Dace Plated 3 Jen 2002 Placing Aliquot: 100 uu Cogncpeerntprlaattieon NPulmabteer pReerveprltaemttes BackCgordeowsd ReAvveerrtaagnets DSetvainadtaridon Venscle o2r 1br0e5d 11 o 21 101 . 100 a2 m154 1i o 203 1 wm 2s ms 0a 161951 11 0 208 1 107 2 --~ 1000 00 1m10 11 0 150 1 ww 393 0o 151559 1i 0 168 i 160 7 5000 0a 101509 1I a 162 i 0 5s Positive Control 2-aaminoanthraa6cens 1.0fyug per plate 003 s7i8e0 i1 sso n BackgroI4ruxNnBodxrtnLraaelvm;aly2caoSdreeldiugchetdl;y rSe-dAubcseedn;t;Ju-MOobdsecruarteedlybyrepdruecceidpitate NPon-Interfering precipitate; IP-Interfering precipitate BSitouRdeylNioa.nceAAS3CH.502001BTL 2 CompanySanitized. DocsnotcontainTSCA Cal wFi-t2h4a8n90: Bacterial ReverseAMsustaaytion Test DuPont-8968 Bacterial Mutation Test Table 10 TSetsutdySNuubmsbtearnce 1d:|: HA-A2S4I8C5H0.SO2001.BTL Experiment No : BL stLirvaeirnMicrosomes :+ NToAnLeS3S DCealtlesPSleactdeedd :: 30.5JaXn 210002 VPelantiingcle Aliquot +: w1a0t0er Cugonpceerntprlaattieon NPulmabteer Rpeerveprtlaanttee BackCgodreound RAevveerratgaents DSetvainadtairodn Venicle 0012 1i7d 11 03 15 1 16 1 100 002 1I3g 11 0 18 1 16 3 a3 002 1i2s 11 03 16 1 15 3 - 1000 0012 21 11 03 21 15 7 3333 0012 116 11 0 12 1 1 2 5000 0012 a1u 11 0 16 1 15 ` Positive Control so01dium azide281.0 ug pe1r plate 0032 1e0s 1i ses a Backgro1u=nNdormLaalw;n C2oedSelightly reduced; 3mdoderately reduced NdP-=BNxotnr-eImnetleyrfreedruicnegd;preSc=iApbistenatt;e; 6=IOPbssIcnutreerdferbiynpgrperciepciitpaitteate BioReliance StudyNo. AAS3CH.5020B0T1L 2 `Company Sanitzed.Doesnotcontain TSCA CBI = 'H-24890:BacterialReverseMutation Test `with an Independent Repeat Assay DuPont-8968 Bacterial Mutation Test able 11 TSetsutdysNuubssbtearnce 1d:: HA-N2S4I8C9H0.502001.BTL strain + Tass cEexlplesrimSeenetdeNdo :: B0L.5 x 10 VLeihviecrlMeicrosones : Rwaatterliver 89 Date Plated : 3 Jan 2002 Plating Aliquot: 100 Concenrtrapltaitoen MPlmabteer pRoervertplaanttes BacCkogdreound RAevveerratgaents DSteavnidaatridon Venicle 0oz 117 11 03 51 15 s 100 0o2 1by6 11 03 11 15 3 33 oozn 1z0n 11 0 13 1 15 s - 1000 o0r2 10 11 03 13 1 12 6 3333 0o2 16s 11 03 s1 10 5 5000 o02 15 11 03 10 1 12 ` Positive Control 2-oramincanthr10a8cane 1.02ug per plate o0 11106 11 108 1 Backgro1u=nNdormLaalw;n 2Co-dSelightly SnExtramely reduced; Sre-dAubcaeedn;t; IGsMOobdsecruarteedlybyrepdruecceidpitate Ne-Non-Interfering precipitate; IPsInterfering precipitate -- BiooRReli-- ance ---------------------- Study No. AAS3CH.50200BT1L. 2 `CompanySanitized.Does not contTSaCAiCBnI 'H-24890: Bacterial Reverse Mutation Test `with an Independent Repeat Assay DuPont-8968 Bacterial Mutation Test Table 12 STetsutdysNuubmsbtearnce Id:: AHA-S2I4C89H0.502001.BTL Experiment No : BI stLirvaeirnMicrosomes :+ NToAn1Se37 DCealtlesPSleaetdeedd :: 31.J1aXn 2l0o02 VPelhaitcilneg Aliquot +: w1a0t0er uCgonpceerntrpalattieon NPulmabteer Rpeerveprtlaanttes BackCgodreound _RAevveerratgaents DSteavnidaatridon Vehicle o021 55 11 0 10 1 7 3 100 0012 7` 11 03 1 5 2 333 o0n2 7711 03 51 7 1 ~ 1000 002 106 11 0 i1 2 2 3333 a02 nn 11 03 1 5000 000312 873 111 5 3 Positive Control o9-ranincacrid8i0n1e 75 ug1per plate 0023 957399 11 306 9 Backgro1u=NnodrmLaalw;n C2oudSelightly reduced; 3=Moderately reduced N4P=aExotnr-eImnetleyrfreerdiuncged;preSc=iApbisteantte;; 6=IOPb=sIcnutreerdfebryinpgrperceicpiiptiattaete BioReliance StudyNo. AAS3ICH.502B00T1L 30 CompanySanitized. DoesnotcontainTSCACBI 'H-24890: Bacterial Reverse Mutation Test withan dentRe DuPont$968 Bacterial Mutation Test Table 13 TSetsutdySNuubmsbtearnce Id:: HA-A2S6I8C9H0.502001.BTL Experiment No : BL sLtirvaeirnMicrosomes : Rsatyliver 59 CDoaltleePSleaetedded :: 31.J1aXn 210002 VPleahtiincgle Aliquot +: a10t0eri peConcentralattieon NPulmabteer Repverertplaanttes BacCkogdreound RAevveerratgaents DSetvainadtairodn Vehicle o012 5 11 03 61 5 2 100 o012 58 11 03 81 8 1 333 0021 107 11 0 10 1 s 2 - 1000 0o21 107 11 0 un 1 5 2 3333 0012 45 11 03 61 5 1 5000 0012 5` 11 0 71 5 2 Positive Control 2-01aminoanthr5a8cene 1.01ug per plate 0023 7726 11 & 5 Backgro1u-NnodrmLaalw;n 2CoedSelightly reduced; 3=Moderately reduced Ned==Etxotnr-eImnetleyrfreerdiuncged;preSceiApbisteantte;; =IOPb=sIcnutreerdferbiyngprperceicpiiptiattaete --- Study No. AAS3CH.5020B0T1L 3 Company Sanitized. Dossnot conTtSaCAiCBnI 'H-24890: Bacterial Reverse Mutation Test withan Independent Assay DuPont8968 Bacterial Mutation Test Table 14 TSotsutd.ySNuubmsbtearnce Id:: HA-A2S0I8C9H0.502001.BTL Experiment No : Bl stLirvaeirnMicrosomes +: WNeo2newin CDaetlelsPSleaetdeedd :: 30.J9anX 210002 VPelahtiincgle Aliquot +: w1a0t0eryt Cugoncepnertrapltaitoen NPulmabteer Revperertplaanttes BacCkogdreound _RAevveerratgaents DSteavnidaatridon Vehicle o0o2 125 11 03 21 2 2 100 002 123 11 03 10 1 15 6 a3 002 2105 11 03 11 1 3 = 1000 002 219 11 0 10 1 FY 6 EEE 002 110 11 0 nw 1 5 ` 5000 0021 155 11 0 51 10 Positive Control me01thyl methan90esulfonat1e 1000 ug per plate 02 91 Bace kgrour nd Lawe n CodDeYon imams iti 14e=NEoxrtmraelm;el2yuSrleidugchetdl;y rSeedAubcseedn;t; J6s=MOobdsercautreeldybryepdruecceidpitate Npetion-Interfering precipitate; IP=Interfering precipitate 2 meme: BioReliance `Study No. AAS3CH.5020B0T1L 32 `Company Sanitized. Does not contain TSCA CBI 'H-24890: Bacterial Reverse Mutation Test with an DuPont. 8968 Bacterial Mutation Test Table 15 TSetsutdySNuubmsbtearnce Id:: HA-A2S4I8C3H0.S02001.BTL Experiment No : B1 stLirvaeirnMicrosomes : Rrat y liver 59 DCaotlelsPlSaeteedded :: 30.J9aXn 2100*02 VPelhaitcilneg Aliquot:: w1a00teryu Cbgoncpeerntprlaattieon NPulmabteer pReevrerptlaanttes BackCgodreound RAevveerratgaents DSetvainadtairodn Vehicle 002 1288 11 03 hg 1 zn 6 100 002 120 11 03 an 1 2 7 333 o0a2 3105 11 0 1s 1 2 s - 1000 a02 118 11 0 20 1 nw 3 3333 o012 1zn 11 03 36 1 25 8 5000 o012 220 11 03 11 20 1 Positive Control 2-o1aminoanthrsazcene 10 u1g per plate 002 57881 11 612 169 Backgro1u-nNdormLaalw;n C2o-dSelightly reduced; 3=Moderately reduced Ne4s-Btxotnr-eImnetleyrfreerdiucnegd;preSc=iApbisteantte;; 6=IOpb-sIcnutreerdfebryingprperceicpiiptiattaete BioReliance StudyNo. AAS3CH.502B0T0L1 3 Company Sanitized. Doesnot contain TSCA CBI H-24890: Bacterial Mutation Test with an Assi DuPont8968 | Bacterial Mutation Test } Table 16 TSetsut.dysNuubnsbtearnce 1d:+ fi-A2S48I3C0H.S02001.BTL Experiment No : BZ stLirvaeirnMicrosomes :: faosnee CDealtlesPSleaetedded :: 116.7JaXn102002 vPelahciincgle Aliquot +: 10p0atehrb Concenxtrapltaitoen Plath Revertlaanttes BacCkogdreound RAevveerratgaents DSetvainadtairodn Vehicle oorz 15s 1i 0 51 10 5 100 0021 86 1i 03 71 7 1 33 oonz 1i0n 11 0 s1 u 3 - 1000 0012 u1n 1i 03 1 i) 2 3333 000312 s 111 s 2 5000 0o1z 7` 11 03 51 7 3 Positive Control o2-rnitroflucr1e5n1e 1.0 ug1 per plate o0z3 123031 13 162 3s Backgro1u-NnodrmLaalw;n C2o.d5elightly reduced; JsModerately reduced N4P-eENxotnr-eImnetleyrfreedruicnegd;preSc-iApbisteantte;; G=IOpb-sIcnutzeerfdebriyngprperceicpiiptiattaete BioReliance Study No. AASICH.5020B0TL1 i 3 Company Sanitized.Doesnotcontain TSCA Cal 'H-24890: Bacterial Reverse Mutation Test withan t Assay DuPont-8968 Bacterial Mutation Test Table 17 TSetsutdysNuubmsbtearnce 1d:: HA-A2S0I8C9H0.502001.BTL Experiment No : 52 stLirvaeirnMicrosomes :+ mRastsliver 59 CDealtlesPlSaeteedded :: 11.67Jaxn102002 VPleathinigcle Aliquot :+ w1a0t0erub Cugonpceerntprlaattieon NPulmabteer pReerverptlaanttes BacCkogdreound_ RAevveerratgaents DSetvainadtairodn Vehicle o012 1157 11 03 21 20 8 100 o012 220 11 03 19 1 2 3 33 0012 115 11 03 11 Ft 2 --~ 1000 002 221 11 03 1s 1 20 ` 3333 0012 113 11 0 11 5000 o012 2184 11 03 v1 18 1 20 kl Positive Control 2-01amincanthr8a9cens 1.01ug per plate 0032 s65e6 11 15 9 BackgroLueNnodrnLaalw;n C2oudSelightly reduced; d=Moderately reduced -- NP4=sENxotnr-eImnetleyrfreerduicnegd;preSc=iApbisteantt;e; 6IOpb=sIcnutreerdferbiyngprperceicpiiptiattaete BioReliance Study No. AAS3CH.502001.BTL 3s `Company Sanitized. Does not contain TSCA CBI 'H-24890: Bacterial Reverse Mutation Test `with an Independent Repeat Assay DuPont-8968 Bacterial Mutation Test Table 18 TSetsutdySNubusbtearnce Id:: HA-A2S0I8C9H0.502001.BTL Experiment No : B2 stLirvaeirnMicrosomes :+ NToAnL0e0 DCaetllesPlSaeteedded :: 21.63JaXn102002 VPelhaitcilneg Aliquot :* w1a0t0erui Concenxtrapltaitoen NPulmabteer pReervertplaanttes BacCkogdraound RAevveerratgaents SDetvainadtairodn Vehicle 0012 114523 11 03 163 1 153 un 100 001 191269 11 0 152 1 159 3 333 o02 116622 11 03 152 1 13 wv - 1000 o021 118960 11 03 162 1 186 4 3333 o012 116572 11 03 40 1 153 1 5000 o0a2 112635 11 03 130 1 146 3 Positive Control so01dium azide991.0 ug pe1r plate 0032 as53s 1 1 a 2 Backgro1u-NnodrmLaalw;n C2oedSelightly reduced; l=Moderately reduced -- N4e=eEtxotnr-eImnetleyrfreerdiuncegd;preSc=iApbistenatt;e; GI=pO=bIsnctuererdferbiynpgrperceicpiiptiattaete oR StudyNo. AAS3CH.5020B0T1L 36 Company Sanitized.DossnotcontTSaCAiCBnI 'H-24890: Bacterial Reverse Mutation Test withan t Assay DuPont-8968 Bacterial Mutation Test Table 19 TSetsutdysNuubmsbtearnce Id:: HA-A2S4I8C9H0.502001.BTL Experiment No : B2 SLitvrearinMicrosomes :+ RTAaLt00liver s3 Colls Seeded : 2.3 X 10 Date Plated : 16 Jan 2002 VPelahtiingcle Aliquot :+ w1a00ter Concentralattieon NPulmabteer Revperertplaanttes BackCgordeound RAevveerrtaagnets SDteavnidaatridon Vehicle 0021 127151 11 03 175 1 167 2 100 0012 118937 11 03 m2 1 184 3 333 o0r2 172162 11 03 198 1 195 i) - 1000 [022 117885 11 03 126 1 163 32 3333 0012 131861 11 03 16 1 160 23 5000 o012 116509 11 03 132 1 150 16 Positive Control 2o-1amincanthr51a5cens 1.0 1yg per plate 0032 774975 13 819 @ Backgro1-uNnodrmLaalw;n C2o=dSelightly reduced; 3=Moderately reduced N4P==BNxotnr-eImnetleyrfreedruicnegd;preSc=iApbisteantte;; G=IOpb=sInctuerrefdebriyngprperceicpiiptiattaete BioRefance Study No. AAS3CH.50200B1T.L 37 CompanySanitized. Does not contTSaCAiCBnI 'H-24890: Bacterial Reverse Mutation Test withan Assay DuPont-8968 Bacterial Mutation Test Table 20 TSetsutdySNuubmsbteanrce Id:: AHA-S2I4C8H9.0502001.BTL Experiment No : B2 stLirvaeirnMicrosomes :+ NToAnLeS35 DCaotlelsPSleaetedded :: 21.66JaXn102002 VPelhaitcilneg Aliquot vater : 100 un C1goncpeerntprlaattieon NPulmabteer Rpeevreprtlaanttes BacCkogdreound RAevveerratgaents DSteavnidaatridon Vehicle o0r2 223 11 03 26 1 2 3 100 0o2r; 125 11 03 hg 1 1 2 333 0012 135 11 03 13 1 12 2 - 1000 0012 u[i 11 03 `1 27 . 3333 [052 11 11 0 11 1 2 5000 0012 15 11 03 pry 1 10 1 Positive Control s0o1dium azide3361.0 ug pe1r plate 0032 336596 11 354 uw Backgro1Cu-BNncoderrmLaaamlw;enlyC2o=dzSeeldiigohetdl)y rSe-daubcmeedn;t:3sM-oodmemcreartaedlybyrepdruecceidpitate NP=Non-Tnterfering precipitate; IP=Interfering precipitate BioRefonce Study No. AAS3CH.5020B0T1L. ! 38 Company Sanitized. Does not contain TSCA CBI wHi-t2h48a9n0: Bacterial ReversAesMsutaaytion Test DuPont:8968 Bacterial Mutation Test Table 21 TSotsutdysNubustmanbcee rTd:: seratn + HAM-S2I4C8H0.S02001.BFL mass CBerlplesriSmeenetdeNod:: 28.26 x 10 VLeihviecrleMicrosomes wRaatterliver 59 Date Plated: 16 dan 2002 CoPnlcaetnitnrgaAtliioqnuotPla:te100Ruesvertants Backsrowd Average Standard 1g per plate tusber per plate vehicle 0 7 TCode Revertants Deviation [03 22 1i s 100 aa 15 3: a 53 un ' 333 aa 11 1i 03 3i 1s s - 1000 0on 1i0s ii 0 7i un s 3333 0a 185 13 a si un ` s000 2o 1s5 i1 03 1i 12 ` Positive Control 2-001aminoant1hr3iatcsens 1.0 v ug 1 per plate 0 Backoround Lawn Code a3 i 128 5 dN1se-E-Nxlortomrnae-lmI;enltye2r-fSseeldriuigcnhegtdl;pyrerSceeidApubicsteeadnt;te;;I6e=IoOPdb-esIrcnauttreaerldfyerbiyrnepgdruepccreiedpciitpaittaete BStiuodRyelNioa.nceAAS3ICH.502B0T0L1 3 Company Saniized. Doss notcontain TSCA Call H-24890: Bacterial Reverse Mutation Test withan t Assay DuPont.8968 Bacterial Mutation Test Table 22 TSotsutdysNuubrsbtearnce Id:: HA-A2S4I8C9H0.S02001.BTL Experiment No : 82 stLirvaeirnMicrosomes :+ NTo1n5e37 DCealtlesPlSaeteedded :: 11.60JXan102002 VPelhaitcilneg Aliquot :+ w1a0t0ernL CLogncpeenrtrpaltaitoen NPulmabteer Rpeerveprtlaanttes BacCkogdreound _RAevveerratgaents SDetvainadtairodn Vehicle o0012 55 11 71 7 2 100 o012 +7 11 0 21 . 3 3 002 74 11 03 21 ` 3 - 1000 o021 55 11 0 31 5 2 3333 0012 7i 11 03 61 6 1 5000 002 s3 11 0 21 3 1 Positive Control 3-o1aminoacri7d9i9ne 75 ug1per plate 0032 754755 11 708 118 Backgro1u-NnodrmLaalw;n C2oSdleightly reduced; I=Moderately reduced -- N4e=eEtxotnr-eImnstleyrfreerdiuncegd;preSc-iApbisteantt;e; 6I=pO=bIsnctuerrefdebriyngprperciepciitpaitteate BioReliance StudyNo. AAS3CH502001 BTL 40 Company Sanitzed. Doesnot contain TSCACBI H-24890; Bacterial Reverse Mutation Test withan Assay DuPont-968 Bacterial Mutation Test Table 23 TSetsutdySNuubmsbtearnce Id:: AHA-S2I0C8H9.0S02001.BTL Experiment No : 82 StLirvaeirnMicrosomes : mRTMaat1sl37iver 59 CDealtlesPlSaeetdeedd :: 116.0JaXn102002 VPelhaitcilneg Aliquot +: w1a0t0erur nCeoncentraltaiteon NPulmabteer Revperertplaanttes BacCkogdreound RAevveerratgaents SDteavnidaatridon Vehicle o012 15 11 03 81 5 . 100 0012 74 11 03 71 s 2 ET 0012 5, 11 03 10 1 5 2 - 1000 0012 s2 11 03 71 s 1 3333 o012 42 11 0 u1 6 5 5000 0012 85 11 03 51 6 2 Positive Control 2-o1anincanthra8cens 1.01yg per plate 0032 78 11 80 5 Backgroiu-NnodrmLaalw;n C2od5elightly reduced; 3=Moderately reduced N4P-eBxotnr-eImnetleyrfreerdiuncegd;preSceiApbisteantt;e; GI=POsbIsnctuerredferbiynpgrperceicpiiptiattaete BioRelance Study No. AAS3CH.502001.BTL 4 `CompanySanitized. Does not conTtSaCAiCBnI F-24890:BacterialReverseMutation Test withan Ass DuPont-8968 Bacterial Mutation Test Table 2 TSetsutdySNuubmsbtearnce 14: AH-S2I4C8H3.050001.BTL Experiment No : 82 sLeirvaeirn Microsomes : Nweoaneuvin CDealtlesPSleaetdeedd :: 3186.2JXaxn102002 vPelantiincgie Aliquot: w1a0t0er Concenrtrapltaitoen NPulmabteerpeRrevertplaanttes BacCkogdreound RAevveerratganets DSetvainadtairodn Venicle o0r 1s 11 0 ai 12 s 100 o0r2 5s 11 0 51 5 1 a 0021 77 11 03 1 " 3 - 1000 0o s2 11 03 `1 2 am 002 137 11 03 10 1 10 3 s000 o0r2 110 11 03 u1 1n 1 Positive Control me0t1hyl metha1n12esulfonat1e 1000 pg per plate 0023 98 1i Fl 1s Backgroiu-NnodrmLaalw;n C2o-dSelightly reduced; 3eModerately reduced N4p=eBlxotnr-eImnetleyrfreerdiucnegd;preSc-iApbistenatt;e; 6I-POsbIsnctuerredfebryinpgrperceicpiiptiattaete _ StBiuodRyelNioa.nceAAS3CH.502001.BTL 2 Company Sanitized. Does not contain TSCA CBI H-24890:BacterialReverse Mutation Test with an Independent Repeat Assay DuPont-8968 Bacterial Mutation Test Table 25 TSetsutdysNuubmsbtearnce 1d:: AHA-S2I4C89H0.502001.8TL Experiment No : 2 stLirvaeirnMicrosones :+ WRPa2t wliuvner S9 Vehicle + water CDaotlelaPlSaeteedded :: 81.62JaXn102002 Plating Aliquot : 100 kL Cugoncepenrtrapltaitoen NPulmabteer pReervertplaanttes BacCkogdreound ReAvveerrtaagnets SDteavnidaatridon Vehicle o02 2u0 11 0 12 1 u s 100 o02 125 11 03 12 1 un 2 333 0021 125 11 0 11 10 2 ~ 1000 o021 55 11 03 51 9 3333 0021 1123 11 0 11 12 1 5000 0021 87 11 0 71 7 1 Positive Control 2-01aninoanthr6a3cene 10 1ug per plate 0023 875408 11 51 5 Backgro1u-NnodrmLaalw;n C2oSd1eightly reduced; J=Moderately reduced NP4=eElxotnr-eImnetleyrfreerduicnegd;preSc=iApbistenatt;e; G=IOpb=sIcnutreerfdebryingprperceicpiiptiattaete BioReliance StudyNo. AAS3CH.50200B1T.L 4 Company Sanitized. Does not contain TSCA CBI 'H-24890: Bacterial Reverse Mutation Test `withanIndependentRepeat Assay DuPont 8968 BacStuermiaarly MouftaRteisounltTsest Table 26 TStuedyst SMuubnsbtearnce Id +: AHA-S2I0C8H5.0502001.BTL iment No : B1 Liver MicrosomAevse:rageNonReevertants Per Plate + Standard Deviation Dose (ug/plate) TASS ma100 V1e00hicle 18:: 21116650+s 167 1033030 1WBi: 1112630+01s128 53303030 1136:: 0315152524 2172 Positive 148+ 20 580: 60 Liver Microsomes: Rat liver S9 TAISIS 1166+: 31 1155:+ 73 1105s+ 24 ess 1 TAISI) 57:: 23 77:: 21 692+ 34 06+ 93 We2 wun 125:: 2 1178:: 63 1L0z: 24 92: 3 Dose (ug/plate) TASS TAIOO TAISIS TAIS37 _ We2 uven 1V0e0hicle 2380:: 52 11871:+ 258 1155+: 35 88B:: 31 223:: 76 - 1303030 2282:: 62 1W7r:: 32B0 1152:: 66 95:: 22 2L:x 38 53030303 2108:: 33 116400:: 357 1102:: 45 65:: 12 2250:: 81 Positive 5914125 80+ 71 108: 7 63: 9 6121109 VPeohsiictlieve==VePhoiscitlievCeonCtornotlrol Plating aliquot: 100 ul. BioReliance Study No. AAS3CH.50200B1TL. " Company Sanitized. Doesnot conTtSaCAiCBnI 'H-24890: Bacterial Reverse Mutation Test `with an Independent Repeat Assay DuPont-8968 Bac`tSeurmimaarly MouftaRteisounltTsest Table 27 STteudsyt SNuubmsbtearnce Id : AHA-S230C8H9.0502001.BTL nent No : B2 Liver MicrosomAevse:rageNoRneevertants Per Plate : Standard Deviation Dose (pg/plate) TASS TMI00 TAISIS 1V0e0hicle 07:: 5111590: :1318 2139s: 32 3130300 L0es 32 11862: 1& 172:s 24 50330303 87:: 23 165: 313: 110++ 12 Positive 162: 35 413: 26 350: 17 Liver Microsomes: Rat liver 59 mAISIT 74:: 32 252 33 63:+ 11 708s we2 uvra 152:: $15 74:: 12 10:: 31 573 3s Doss (ug/plate) TASS TAI00 TAISIS TAISI7 _we2 uve - 1V0e0hicle 333 2210:: 38 11087::121 117:+ 87 7+ 2 195: 18 16+ 5 66:: &2 1m4x: 25 8: 2 102 2 10330303 5000 210+: 1116032:3223 111:s 56 20: 7 1501:6 12: 4 s6e2 15 192:: 41 6: 2 7: 1 Positive 619+ 93 819: 87 128: 9 80s 6 7573 8 VPeohsiictlieve==VePhoiscitlievCeonCtornotlrol Plating aliguot: 100 ul B-i--oReliance StudyNo. AAS3CH.5020B0T1L 45 Company Sanitized. Does not contain TSCA Cal - Hwi-t2h48a9n0I:nBdaecpteenrdieanltReRveepresaet MAustsaatyion Test DuPon-8968 APPENDIX A Historical Control Data BSitouRdeylNioa.nceAAS3CH.5020B0TL1 " Company Sanitizad. Dossnotcontain TSOA GB - 'H-24890:BacterialReverse Mutation Test withan Independent Repeat Assay DuPont-8968 Historical NegativeandPositive Control Values 1998 - 2000 overs peeps Con[ew |5D[i|Wis|We {5D | vin|ie| TA Tato E wn 1-313 SE aa alEeA 35 _-- 206 NE) Po 568 et12 as] 1371 1 322 sa rl as 736| 301| 198] 2871 7 29 38 317 SD=standard deviation; Min=minimum value; Max=maximum value; Neg=negative control (including but not limited to deionized water, dimethyl sulfoxide, ethanol andacetone); Pos=positive control BioReliance `Study No. AAS3CH.502001.BTL 47 Pre oe - wHi-t2h48a9n0I:nBdaecpteenrdiealntRReveepresaet AMustsaatyion Test DuPont-8968 APPENDIX B Study Protocol BSitouRdeylNioa.nceAAS3CH.5020B0TL1 " Gampany Sanitized. Doss not contain TSCA GBI --_ 'H-24890: Bacterial Reverse Mutation Test with anIndependentRepeat Assay DuPont-8968 Rec bye RAIi OA_v 1-Reed " B`iSpoonsoRrPrSeoujdeicytNaNuumnmbbecerr::__DAAuSIPCH4oL96S8s0B0Ti0L1 -- atiotmhab depm enRedpteneetn iAnsostnyreAcPPPPRR(OOV2E)D `e TeSoerlnpiounnrepgolksap eptspofhsdithhniiasts1e eito0nysfofsde$oe9sce caei0vteosen.otuhpeeaimonsoscagtofpaoEtcixdJioofttofecooelvtlWsPisticoeeybboynf 20 sponsor 2 Name EX. duPoot de NemessdCompany 2 Add DSui0no.e5Hs0aHxsa5ks0ekelRleLaebor Cor N1e0v9eEoDnERe1n9d714050 FER -- PMa[rosa:D3o2gn3a0,e0520]5.1 _ 24 Spon Pj: EmDauirlt:amsareisadonnerGre dupontcom sw --- 26 Han Haus SE 30 IDENTOFTIESFTANIDCCONTAROTL SUIBSTOANCNES El] 53 Cont II ere PNepiuieve: Taetmbcierveils | m22myi]tnmhniieo rain PracaSPOTSION Lim01 Page ofl BioReliance Study No. AAS3CH.502001.BTL 49 @ BIORELIANCE - Company Sanitized. Doss not contain TSCA OBI - 'H-24890:BacterialReverseMutation Test withan IndependentRepeatAssay DuPont-8968 Bi`oSkpoenascorePSroajeyctNNuuombbeerr::___A_SDIuCPoHatS$090681BTL 34 Tox SubtmeChmctinion Uornoeppseorntksetfemorydesatenrmogifneatnthieondosroiednmgaddosenh,mtsnieeomsnis.toTinnhgeofSfcotenasaiBwyiolaklebpdtyowmyiold cb omposionntc hoefsthveteets 0mvbeehsi,) ud he sayandsven of ht 55 TouSubomce RetinSemple: TShepreencoofa sevespi fett tewil bsth epomsiltyof 40 TESTING FACILITY ANDKEYPERSONNEL a Ne TBoiiokoagiyaeTesi acy 2 Adds 9R63o0ckviiaMllD,C2a08t5D0erirve - 43 SwdyDir PhVoe:in30.61W0a3g1e5r2TL,MS FeRLTRDG Email: swagnen@biorelisnce.com 50 PROPOSEDSTUDYDATES 51 ExpaSiurnDlu 21002001 52 Expuinon TamiosionDue: 06555202 53 DutRepeDue: ran 54 FilReportDu: 2 ek terSpcsprdiea. 60 TESTSYSTEM TVThAe2ItSs3sSrteddmoTAseIiS3il ahbydeeescrintbhedne.byMApamihelsa1c9na7.0,i(1s97i5n)sand cit.seTfASsS,eTSAoIi, [CRoowtse[TRemCators|]modnoss| wpTe |a195T|aRemi|[Rotator| PrccSPOTSEOl Limo! Peet @BIORELIANCE SBtiuodRyelNioa.nceAAS3CH.502001.BTL 50 Company Sanitized. Does not contain TSCA CBI - w'iHt-2h4a8n9I0n:dBeapcetenrdieanltRReevpeerasteAMsustaaytion Test DuPoot-8968 BiReSploinsoocrePSrtoujdeyctNNuumbmebre::__A_MDSuIPoCnHtS49062805071, [e[RTrs Eopa sae ntos | C 1 wI mT a] Tae [= | Eopaetcrahotin.o,narpdhdeoisn mmtaeelsstowernaslslitehn.icocnonsbiannc,eisnaicidrvaitscysttthooe8pseonnesea.taTioansigneotsfhie.Tehchillsf0ss aebxrceiisviniocnsleabspeesicxoscfydcenhdi..cTTahesetedsrecehsdion5nsihnTeAthOecwoanordi,nTpgeAnTeOaDesslroincg,oiymiacdnteheithpnKwMDoINuOlALd SpCalomeipdet(vly1vimenadggwteihhesRhb-efymamoicdeci.fhyIitnbgas0beeresnosiesn,ogbtaockithlaDtNtAeprlepaiodmceearses inTdAeSpaSeanindfdenscTdeA(bIpSe3oaouepbeyeuv)eiobyn fmotnegseinsssiamnaTdgAeeTpSsenS.dSeTnicAreIe(veerimexdoroopeyyv)beyformbhuytnibgeeonntdsh cosebse bition. - T5o2l0in(gWcioilnnse3tdee1riasci,ictn1D9Nh9a0As)eaTnxockAieTrbsasappneeicWsFtstch,cTirbycapop5shdaatneioivnensrieanwhiecairathihefrodoEe 1C9hvoebmiaensmochneacncgiehnaaihsheescoririgvginieaalliy>mbtatusiondpaisbiueionrpaebiyoen+sbuatTacoohnas,ng(eOcpreaewcnbietryMiormf io,s 6. TNhUueonSn. piCpoolhvflieCcmtetiaoannsooften,istBeiretrsklilyneyss.TdvehrMeareiceolsiBlvadecedari,tAiybefrwoiamns,rDSrco.oBvrtu.ncde(roAmnUesd, Kingion) 70 EXPERDESIIGNMANEDMENTHTODOALOLGY WToEchge2atittvrs10vdiipsi20wdvivlciobnetttrooelsSdwaittvheiieoirs.oiAloslfdfToivAeedS,voeTvAeTeoODsf, tToAsnIg$b3i5tihT,pASonSe]pgaadeie controlstd osscontwill pte pie. Procol SPOTSO01 Lim2001 ge of11 StBiuodRyelNioa.nceAASICH.50200BT1L.. 51 @ BIORELIANCE `Company Sanitized. Does not contain TSCA CBI - 'H-24890: Bacterial Reverse Mutation Test withan Assay DuPont-8968 SponsorPctNur: _ Duponk$968 BloRelsceSeyNumber:_AASICHS02001 BTL 74 SobiltyDeion dUcnewlmerisksnbatilhoeenSwpiplebane ncoownspducitend ac0sdaintnhoift:tSOmmRbooncfeso sqvhloces,closmrobmlly 5oT0r0IkmLgo/Lfn,p.rfdeofoierrm,ainsovndeiehd.iebu.t(VseClAeiSc1ke6s7c6o0m5p,nsdstno wdditbhn(zCAesSdt6w1ye1a75(sCaAnSd Ssooccrokknocoefo(piCnrAfcSeer6nc7e:,,6v1wp)h.icT0hhp0eovmriancslep.oefefopcahriooocnnwosillhebeglthseest24twee0k,0scbgofcreod.nbflo1re 72 Primi ToxeiyAssy oSelectDoeLevels S2eS0cypoTnehoasfpdnroeeipemovilerseyfsoorfytheetvaoistllibccaossnatydwsiblydobeaorsdkvipTAtGdy, oeTAlcIy, cTcoAnLcenSt,oifoTn5AsLosSf)atitwaun.WcUF2n,isaorihetPoceleepaeatteGiroevcironbbc a.baSdtyhot0merp, brcoebkscog _ doilceleovvdiilSgbmoaptfiedilicig.ne1hsswwisoilrekcabiebnlcgeodcpoloovsyeeJrd.vDofcnsoowthivlembiaelnspfleSechdyesotu mryottht eidieofnowrethcedeoidesinnogt5gmfeprelnwiFwhiomlrlaoredlsy mcring1u,,iWoehseoewmeapototismoebn,baofsrio,nhleGoy {H0i1g00heimsgthdortvtdwoesdvoevlmllvlweib.llTghc eSlpeon:sn orFowrilplbeeepopiptnftgi,ipeogpunreisopgbdteosesmleeyi,n Ile7ev)eltsheecshthanonmem3mndggostlsvo ls3)stdleovivbenmdnh0o0apeebtietitotnssato o ddor 73 Frsag dRoeuofAdciisnyion mT2ehto0hAotdmtolssog(yr193iw)gi.uTlhllbiyesdetexetorsneyd0bsyhbAestebstesbscho(ew1s7tvo9idtaeetppladeawicevoyrgpoeorooifns lacsof hemi mags(om. 1975Mianod A,170, A5SllbyeoswtehievldobetderfpeoifrtThnetdnhyeoefiesvssetshwye dSativuneybDeiesrnvniddeesdre,mybwiieslmostsgesecrticy Tevesshoudbechang etm voleps, nceyoicyor Proc SPOTS B-i--oRelisnce 10402001 Pagedof11 BIORELIANCE Study No. AAS3CH.502001.BTL 52 `Company Sanitized. Doesnotcontain TSCA CBI - H-24890: Bacterial Reverse Mutation Test with an it Assay DuPont-8968 BSipooRenasnocrePSrjtecytNNuusmbbeerr:. ___ADAupSoInCtI39L6S80B0T1L (cCGx8.cBi1v20evpaceoimoppseoys.s),IoihrewSnpeoonrnamaimnvcwirdl)boefThleiesipdiimnnaeebriebresqiovscnomcyts `POGhEuatCmiDaocGceueisdieoclnitnse(S4p57e9)c7i(,beopAtspeclsy 1o9f9aRdeppubaliysh GFeemrinniyd1s958Taod131 2 Cons 741 PoiCones Aildcoemba iomioy n of pose tbievelocw:rtsdeesispled concureatly 5 I=E=PJo PEeE IeTr [rzma | [1 TTaaISmS,S [2miofuoree175] = = a -- 742. NegativeControls Ailphrsookpthr$era9esaiecpi2aviavboenic.soTohnnetbesgiaslilbfveeopcreoeduooffltohiclachbcetitrdhsveiinccwi.tsh stohl. Iai cae,Sot wordsdei sortwil od 743. StyCoots Tlhemeecthceoemoernityt:tmie tionsodteSh mod 9 ies 75 ExopensMetolcActtion ATi hoe n5sbi1n25miEipanmdopeolrntebvnerre9ceiopinlrolfbeeAsrnscdt1lc1e1S5m4a,e5gt00iDmcevgci.Bveedsosyypnanr.d osm.Th 59 willbebch predandsor Boe sorbet Proc IGTSO01 1dnzmol Paget] @ BIORELIANCE BioReliance Study No. AAS3CH.5020B0T1L 53 Company Sanitized. Doss not contain TSCA CBI - 'H-24890: Bacterial Reverse Mutation Test withan IndependentRepeatAssay DuPont-8968 SpoorProjectNumber.__ DuPont4968 BioReSltuidysNuombcere: _AASICHLS02B0T0L1 7mm e0abolia ize0l2sSadmg pi.cmEoacmrthi iibrouancheTosc efAI9ah.og7e13rdmewbiylllbsmsstsefmoes0hyfobso Incomneatn.aely1p0r%io 159we, tDoeno9gweisltl,be thSawmedad$iheoodmwbigthhepctoec,oposob0 m2si100imilMlboec10b0tmtMipbednipneuclaeotfim7dl.e4rphTiohsppHhdat7e.e4,.homiMdMgdaCl ano5d3i83miMoeK.SCehin 76 PrpaiToeenrSoifn OPvihemsepipghrohnpceriunarehefsoefwincloslbobceakiinnToiolcuobeemfecosomhntahtece uspbpneopsrarisrttcrbmdas.verpteeicboodioffoJom 10rp0miengodpneyryscaa1ec25h,vT7hmsa1ke3r74nf2c-ukCbepVtiorlrlwoillxbdeypr1o25gbroawmismneedgr1ekbtehgeemsctbipiaged priori? - cnAo icoorrseoesfeistslhkbievbyheyarvtioeosdonbofymsacnaogbecir.ntnuosspehwtmiooss1torfoecmooeofvcesiioctcrne inca dey of pen1nsryl. 27 TeaSyrendotcstion SiahcihedpdloOiawliplwbi,eebkPeersovrinith.wcdosdesiysanthpee5idessrhbeofdtabBionek,esrt 8 TouSubst Pearson Ulresesoi0ao risenetsktg elibsisovnilbmeppepeiids 79 TroTemtSyas 2O500n,auoloffmvmiiollliee,rst(0it5msvLoe)boeofpcs3eglioo4rS5hoap.mosiWtih,veenc1so0r,celomf itl rbicsandidsdsnhd0e oofgrtectc mibnedtsdo aoverct n ostbrciaisec e!iccewioslflosb2e co5Bi,fLse.sou.ofsiTa hoiiefslicearl evewniSsle0elm5o.e. Proto SPATS 102001 goof11 @ BIORELIANCE BioReliance Study No. AAS3CH.502001.BTL 54 `Company Sanitized. Doesnotcontain TSCA CBI 'H-24890:BacterialReverse MutationTest with anIndependentRepeatAssay DuPont-8968 SponsorProjectNumber,_ Duo 968 BioRStedytNucmbeer: _AASICIHLS02B0T0L1. Aofprrotxeimoavya4r8y10ha7s2shoolwisd,37h4e 2pe.eas wsitlhbe iver llovingtenbeionpidwilbesored 24 randdistndlfor 0 Sern 1{T2h05ehscoetgiueinveofcctohueyrbapitrelacbdcpkcog,rrdEoevdiddseenlwcoesgwoiwflivlhbeycarwetivleerdveedfsocrooeuvtidfreernaceioovefk pPpricepcpilaTtoiosinowdiwlillbiebecieabnaotrai1rmppdooemerrnacneuebou0ifobBnehpaiamcdbtebaoylvftoewhsrrvotmumcircfiivon.s Vibesmgpicason 1 TesterSnVesiftion OChnotchkedrayefsepeeinntthepouen ti ayi,dail 6c0e.r tn ceswil be 0 CRITERIAFORDETERMIOFNAAVATLIIDOTESNT hefollwing rier tbcforthe tag say obconsideredvl: - 81 TesterStainIntegrity c{iTeoedesrmonisxetncotnih,etprcpaicoieuotfrthce yfslvkeiveonrti,.Tcloaldboepnaiskreitehhpsmrtrescsoihf {{{heoesvepienieneuiofgrthhespTioRdMeIsOccpaabisdehonircekat,coeWofrsiosr ghbiTteiooodnf,eTmiAoSncsao TATOOmtcitstm peli: 82 SpRo eve uBcs kgre dFros (Bncuidcii.oomThmenmaeimabnaerroefcvoeprutorscpdreo,pealvmtarpsiFtiiicoGtloohreesparvisinetgsrconuaglis VGeozcoen:, 1T0A-SS6,0 10-50, TALC, 0-240 TALS3S, 5-45; TATSS, 3-310 8 TerminTies Tiorcsame bthetscpr0eermutbehroOfb1ac0iselsreppolle,elrkersicue ProcolSPOTSTONN 1a2001 ageTof11 BIORELIANCE -- BioReliance Study No. AAS3CH.502001.BTL 55 `CompanySanitized. DoesnotcontTSaCAiCnBI - 'H-24890:BacterialReverseMutation Test withan IndependentRepeat Assay _DuPont-8968 `SpPorojse sNosoberr_ Dueta568 BioRelsceSudy Number:_AASICHSO200L BTL. 84 PositiveContVaan: Beacphmieneponsigviovneocovmlo eckte(caeb ha)scth1.e0s6reeseocr he 5 Toy oAfdaroeemevaeesspfeorrpelmebeeoa-virecedotsheeceoeleswni5lgl0abo%ecicomdomenr0vncea(uesnacnsyidotosn. m+oetdebaelocsoamnrpaannciheikdveby,adenarlltvd.poreidoenpeoonfvden droelpyiewitlhloormretvpeaetcsowitlhoev opiecharge indoe evel 50 EVALUOFATETSTIRESOULNTS iCFmoraeoevtennttsoafnpcceep0lsbeeouvfalbtntopoeoscinttivke,rlsi#ow5:stccaes Bdioseodftceeseinhge 91 SinaTAImdSTAIISS? - Dthauenedeocisewlielpl.bse deodqposotivernte mBcnr3a0ei-6cen vertiep prkoolf 92 SeisTASK TAIOOmad WP2rh Dhauetedo(teiweiclipl.bse ogetdposoi ri ssiamnr2a0n.m5c mveentctoeepckoolf 100 REpoRT SAicoroplry:ofdehscorlsmofbiosdssvyedwfilxgberenaiorn 1b2ymeTyeionf LabdooreTessdpwoiltl + pTreeutcSandpsbtic:mpraeiinonniopirnopaenyrdCASleova,lfoktneownsssyeodBseSrysodIpfkein,oift + Sboclveeinast:uhsiinrifforewh.iceof eliesoit madsabi of et + Stns:sosvk mberfell.prele;sncharsciiics. ProceSPOTS Lima2001 Pugs Bot11 @ BIORELIANCE EE omeeereeeeeemeeeessereteense StBiuodRyelNioa.nceAAS3ICH.502B0T0L1 36 CompanySaniized. DossnotcontainTSCA CBI - 'H-24890: Bacterial Reverse MutationTest withan Assay DuPont-8968 Spor ProjectNumber: _ Dun 968 BiRalnceSty Nuber:_AASOCHLSO2B0T0L + Tnotecrooifnlsat:esmpofusrnctoonttbo;empodsecphertpoldve s;yiphemmodcc oimdpoeosofetlmeiceiobonoslnoc + Rneemamein,oifgWrsheovefertrxptoiscshciyib;lseei;gsnssopifespiprctpealisynsoidns;,siiafnnsddyievd;icdGoepnvicldueirocn;oudtsoesgtoahrieevpeoenmasaned pCooiuirvetconweihdangec,asnasndwsdseadnddevdiavtiron.;Notoiclrepaive od pose + Dicusiofels. + Conchion 110. RECAONDARRCDHIVSES AUrwdu,theproce sdall reposwilbe itindaconfoStandard BOlpiodelrRealctcliairnngecParn,sodoc14eft7doe2ru0raFeBoJrOuoPtcQaPrcp3t0eoR4noy0dobe,yeoRfotfcthkseevBimwilhloaeRii,ecMlltiDsia2noA0ec8leh5lRe0AS.QPptAyeo.ohruiniswiStiOllh7se,ardpecqnueuacmrsetedrrdfeeodctfaehot:r SpBonlsorodmeeshtRirovysedoerwillisorsnubeomfc1opgiyeeodusnadthe copywal bo rainedin hs - 120 REGULATORYREQUIREMELANBOTRASTO/RYGPROACOTICDE TTGohuiiicdstlpilnroegos:c.fBobaeacTsaebmleieRnewovfieChteMruttioaetci,oompnpoAllsyeaw)di,bhNyOiGEsEhCCDA,dGPduaiedsce,hlFiennerto4y7t1 e1(9OG9B8esCtiDdc ReigtihstrhueiIonroif orann!maConferenfcoeronenHeamUosnei(m1i9o5n6tnodfT1e9c9h7nica Requinncssfr PTrahpcirtoisccteesRyseppiailstelib,ootnpheserrffoworrdNnoi,ntclodmlpploiLersikbiwaitrlhltyOhSeemeeasisdise(GeoLfP.hSeTGhoaeodprLOoaptbeoonrnsi,onragy iPcrnooccpoohiunces w(wiSilOtlhPbG)eLoPpfe,BctioohRrSamleOadsPfcooeftbyittohReetlQhaancelaeydAlsahceeahoycypUrorrcoetodouf.rDeTitesnRilnipyrcsotsecomsrss Spnodyrisrpnegcwifitihclepalhisyat,hetA.ssepydisesdQpoAfscsatchesienpsscpweilcdl,bieannngdctlthohedeeddpufeenrshiteohBeoeqlularpsootfTctahhcesh aSienmmnpeec,inonwwiienlrecrdeeoOtrLhieePdcGoL0mtpPplhiiSanltciye nsDiaentwtiatwhswiahdlitcbeeh SnhlecsoydDydiiInestssoomplasapopsrnto.odT.ahim1sy orrscpiitoyn noltyiscofmpleianceetiofoprpclblea,nbctlodinog tkhemiiisoh.ofcpmciinion Pron SPOTSO01 Lan2001 Page9of11 @ BioReuANCE BioReliance Study No. AAS3CH.502001.BTL 51 CompanySanitized. Doesnot containTSCA CBI - 'iH-t2h48a9n 0I:nBdaecpteenrdieanltRReevpeerasteAMsustaatyionTest DuPont8968 SponsorProjectNumbe:___ DaPont4968 BioRelioceStdy Number:_AASICH SOROOLSTL. UnolfpfeoossllesorwoninfggtemlmieistiossrSureirooanoetonbhefefeecsotnyrpeeoy,n. isdldloriengnaclhietnsbwielalnbesdiwplonbeed 130 REFERENCES RAmenedcsm,aiBhnN3g1.s3M4wc7i3C6ha4n,S ,J.sd Yl amaki, o (157b5o),sMoem nthsodTsAfoNrda etainockn aMrioings rc m,Mh LLo.i.sMi modtMiaornlc R,sWeoc,ho 3(8139.7363).Mage esi wingty'reversion ia RRIeetggrluiirioyonnGoefCnoPtnhoeariecrcymeaTeecnsosHloaerorhmaHicasaaomcnetUis(cCeiHs:).OSoufAkedTnecsohoiancaSlpRaeccqeoieAmmpmeneossdofoofr adGoipTtaiio5n81a6t2s0e,pAi4t. o2f6t,1h5e5I.CH procesonJay 19, 1955. Fede Regier R`IeGgteimbsaoriunioioncnlyoTfCsPoifnaegrroocfcsPehloanassHfcaoorrwmiuisrs.noSan2U.s3ed(.oIcCGuHmo)eocnftnTsecyco:tmieAaSnatnReiqfauoirrsBeomaepntys ffoxc - Rsevpe4mtoefr 2h1e19I9C7H proces on hy 16, 1997. FederRepoer621602616030, UMS ScACTain9J,5.0a 9a5d0Ans,em Bs:Xi.(n19o7f60)o ,0Detcechtiotn a :of dcaarmiaoongen .ePs ro5.Nsailns Agscin$t0e. mMoSaCiogoonnn1mi,aCshnoeasS , ,roYnaa ma, .l sdtAmee.o s,BeNy.ofn (139079c,eDeme tieecitosn oPn fr cuNraongAscos.s: MTaeM ra,DMi anRdeAmeo es,B11N3.1n 7(31291835,.Revo MotosfortheSalmon Msg O`PBAadCsdDaFGeurriyhne1949O87E,1C(DGGeuitdielciTnoesvifocrlhosg:TBowaicnkgeorfsRCehvrerasieeMli,tbailosnhTdebsy),ONEiCDs,h WSpielrcmeoa,enn7. Npahiidoro,A,TWAeIGdEd,wDiJth.ExscnhderGicehclboolals,WEDG.te(t19s%o)i.nCs.oMmgpoanncsofs PracaSPOTSUOL 10201 Pageloot11 BioRelance Study No. AAS3CH.502001.BTL 58 @ BIORELIANCE CompanySaniized. Does not contain TSCA Cal 'H-24890: BacterialReverseMutation Test withanIndependent RepeatAssay DuPont-8968 0 APPROVAL Bi`oSkpeonlssocrePSrotjecytNNuummbbeerr::__A__ADSuIPoCnHt8S906280B0T1L Koo Don TT SponsorRepresenmstve Or-Dec-200: Due Weocio Dennec T(TratorTypeName Neduchiiae O. goon7 --17 D= ecaso Lek x 178ec 200) i The Prac SPOTS 12001 Page of11 eR. StudyNo. AAS3CH.502001.BTL 59 )BIORELIANCE Company Sanitized. Does not contain TSCA Cal 'H-24890: Bacterial Reverse Mutation Test withanIndependent Repeat Assay DuPont-8968 APPENDIX C InformationforJapanese Regulatory Agencies BioReliance Study No. AASICH.5020B0TL1 60 Company Sanitized. Does not contain TSCA CBI - Hwi-t2h48a9n0I:nBdaecpteenrdiealntRReevpeeraste MAustsaatyion Test DuPont-8968 ReportofResultsofReverse-Mutation Testin Bacteria 1. Tester Strains 1) Procurement Obiained from Date obtained 10November 1998 tDhaetesiinsnpelcotteidn storage TALS3S oe] cua e ares TAIS38 - pSrn ey rt WE2orrh (@kMI01) Dr. Bruce Ames. NaotfiInodnuasltCroilallecstnidon Marine Bacteria 11 August 1998 markers for each confirmed on the We2 (pKMion) | Averdesn Scotland [Top 1993 @) Storag Composition Bacterial suspension LomL DMSO 009 mL 21.) 5S9ouMricxe, Storage Temperature, tc. of $9 Ee EE BSitouRdeylNios.nceAASICH.5020B0T1L Name and model of | So-Low, Model 61 Company Sanitzed. Doss not contain TSCA CBI - wHi-t2h48a9n0I:ndBaecpteenrdiealntReRveepresaetMAustsaatyion Test DuPont8968 (2) Preparationof9 Specitee. s,SSetraain| Rattus nornvegiycus, Sprague [we [ae]oe| `Administration rane ge (in weks) Batch R65) A odmismou | $03 mie 1871g(0Ba2chR76516)| (g/kg weigh lyweight 3. Preparationof Test SubstanceSolution mm fon | Manufacturer aGnrdaldoer Purity (%) --~ Water (CAS No. 7732-185) InvitrLoifgeenTCeocrhpnoorlaotgiieosn,,flonrcm.er_ly_|| 11110131037223; [ poo0 Stabilityoftet substance w`Mheetnhotdesotfssuubsspteannscieons | Not applicable dificult to dissolve BSitouRdeylNioa.nceAAS3CH.5020B0T1L 2 Gompany Sanitized. Dos not contain TSCA Call - wiHt.h24a8n90I:odBeacpteenrdiealntRReevpeersaetMAustsaatyion Test DuPomu#968 4. ConditionsofPreculture [ romemoon | Nem [wemfwnrsr[Lovo | Oxoid Nutrient |peocd [eo tttprotue| iStonraogectiumetolabneadgittnenmiipn.ogfonrfom | 20 5 hoursatambienttemperature shaking culture eSntdoroafgce tuimeltanotdstueemfpor.rftereosmt_|<8Bours8:2-8C Msohdakeelrand manufacturoerf | Ne Brunswick Scientific,modelG-24 a ee (Msehtahkoidngotfyspeh,aksipneged, etc.) Culture vessel (shape, [[cuoewome Rotary (125 rev/min. J : cyl [som 5. Agar Plate Medium 1) Top aga a oe |owTs e ] [oo[ roowsokse 2) Minimum Glucose Ag Tm www `Made in-house: Au [Mam| foBecrtonDuickinesonr| 1o0013DKSQ Vomogee min |me] SBitouRdeylNioa.nceAAS3CH.502001.BTL 6 Company Saniized. Does notcontainTSCA CBI H.24890: Bacterial Reverse Mutation Test with an Independent Repeat Assay DuPont-$968 6. TestResults - Judgoeftmheerensultts [opm [rege Reason forjudgement and refereatial maters: prNeospeonscietoivreambusteangceenoifcrAesrpooncselowars-obisrenartdvieuvdwecireSt9hd.any ofth testerstrainsincitherthe Referential matters c"oTnhneevcethicalnedanwderpoesciatpiavbelceoontfrodletveacltuiensgianmdiuctaatgetehna.tal testerstrainswerefunctioning BSitouRdeylNiaon.ceAAS3CH.502001.BTL o" -- Company Sanitized. Does not contain TSCA CBI