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| AR 246 - 3229 | a1 | ARARG _ 3427 DuPont-8867 TRADE SECRET Study Title 'H-25170: Bacterial Reverse Mutation Test with an Independent Repeat Assay Authors Valentine O. Wagner, III, M.S. Michelle L. Klug, B.S. `StudyCompletion Date 11 February 2002 Performing Laboratory BioReliance or 9630 Medical Center Drive Rockville, MD 20850 E. 1 du Pont de Nemours and Company . DuPont Haskell Laboratory P.O. Box 50, 1090 Elkton Road Newark, DE 19714-0050 Performing Laboratory Study Number 'AAS2XK.5020B0T1.L `WorkRequestNumber [em {aService Code ~~ Page 1 of63 H25170; Bacteria Reverse Mutation Test with anIndependent RepeatAssay DuPont-8867 STATOE F CM OME PLIN ANT CE Study No. AAS2XK502001 BTL Regulationsaspublishedin 21 CFR w58a,stchoenUd.uSc.teEdPiAnGcLoPmSptlainadnacredws4it0hCtFhRe U.S. FDAGLP 160,and40CFR P7r9i2n,citphlees oUfKGoGoLdPLCaboomrpaltoiraynPcreacPtriocgeirnaamlmlem,attehreialJaasppaencetssewiGtLhtPhSetfaonldlaorwidn,gaenxdcetphtieoOnsE:CD The identity, strength, purity and composition or other characteristicsto define thetestand control articles havenotbeen: determinedbythe testingfacility. Thecontrolarticleshavebeen characterizedaspertheCertificatesof Analysis onfile withthe The stability ofthetestandcontrol articles hasmotbeen detebyrthemtesitinngfaecilidty. A`ncoanlcyenstersattioonodfettheertmeistneantdhceonutnrioflomrixmtiutrye(swaesraepnploitcpaebrlfe)o,rmoerd -_ b`nyottpheertfeosrtimnegdftahceislietayn.aTlhyseesSopnotnshoertheastssiunbdsitcaantceedmtihxatturtehse.yhave ``mTihxetsutraebsi,lriteysopefctthievetleys,tahnadsncoonttrboelearntdieclteesrimnitnheedtbesyttahnedtceosnttirnogl facility.TheSponsorhasindicatedthatthey have notperformed `stability analysisonthetestsubstancemixtures. Notastize 0. Wogar, T= VSatluednyDtiinreecOt.oWragner, III, M.S. biel Af > BioSRtyeMlanagnemesnt Ul Feb 200% Date 1 pak 2002 Dw BeRdmee --_ Study No. AAS2XK.502001.BTL 2 Company Saitized. Doss no contain TSCA Gol 'H-25170: Bacterial Reverse MutationTest with an Independent Repeat Assay Quality Assurance Statement DuPont-8867 Study Title: RBAECPTEEARTIAASLSRAEYVERSE MUTATION ASSAY WITH AN INDEPENDENT Study Number: AAS2XK 502001 BTL Stady Director: Valentine O. Wagner, Il, M.S. QTuialsisttyuAdsyhsuarsabneceemndoinviitdoerds netaoch sofetehess ofpihna-spersoocveesrsphsaseeiss.oUfsistnugdies,Parocensdaumrpeld,indgocosupmepnrtmoacthi,on, `hoequUiSpm.cuFlDrAecoGrodos,deLtacb.oarracteorxyamPirnacetdicien Roergduelrattoiosnusr(e21thCaFtRhe$8s)t,utdhye iUsSpSerEfoPrAmeGdLiPnsac(c4o0rCdFanRce75wi2tahnd L4aS0btoaCrnFadRatrodr1yO6p0P)er,ratschttiiencUgeKaPrnGodcLtePodsuRreerse.egthuatlthteahsettJaadipyaonsecsnoensGduL,cPteSdtsancdoarrdd,iannd1tthheeOpEroCtDocPolrainnd rcelieopvfalnGtoeosd "Th followingaethinspectiondite,phasesinspected,andreportdaesof QAispectionsof hissud. PhIansspeoctOn~~0P6ro-tDoecco-l0R1e-v0i6e-wDec-01To StDiu06d-DeycO1ToMgnt06-Dec-01 PhIanssepoctOn~~ T1e9s-tDeacn-d0o1r-co1n9t-rDolecm-at0eTrioalSatdumdiynDiisrtr1a9ti-oDnec01ToMgnt 20-Dec-01 IospoctOn 30-102 01-Feb-02 To StudyDiO1-Feb-02 To Mgnt 07-Feb-02 Phase Draft Report. InspotOn~~ 11-Feb-02- 11-FTeoSbtu-dy0Di2r 11-FeTbo-Mg0n2t 11-Feb-02 Phase Draft to Final Report "rTeiflsecrteptohretrdaewdsaitbsoftthheemestnhdo:dsandprocessesused ithe studyand thereportedrsulsaccurately Blah SdLatpoour 5u3. d QUALITY ASSURANCE _2 B_ATE\F0 eh na _ BSitouRdeylNion.ceAAS2XK.502001.BTL 3 CompanySanizad. Donoscontsain TSCA CBI H-25170: Bacterial Reverse Mutation Test with an Independent Repeat Assay 'DuPont-8867 CERTIFICATION `We,theundersigned,declarethatthis reportprovidesanaccurateevaluation ofdata obtained from this study. tometySuyDiccr:._ NolOa.Wisgank,Ti= c 1Febesa Valentine O. Wagner III, M.S. Date StAupdpyrMoovneidtbory: fa Dora `Maria Donner, Ph.D. `Senior Research Scientist 0g-Feb-2002 Date -- BioReliance Study No. AAS2XK.502B0T0L1 4 GorparySesed, SoA INTERNS 'H-25170: Bacterial Reverse Mutation Test with an Independent Repeat Assay DuPout.8867 TABLE OF CONTENTS Page SAT commun PU sssmnmmmmommm------------------. (Characterization ofTest 0d COBOL SUBSIANGES...rvevrrorvrsersesned) MBAl M s s mn CU snmmmmsmmmmms--------_ BAIL vncmmmmmmmssmmmmmmmmmmmnmmmononn 37 DESTnmmmmmmmmmsmammsmmsmmmmommmmmmmmmmsmnocl - TTaabbllee 21:: PPrreelliimmiinnaarryyTTooxxiicciittyyTTeesstt iinn SSaallmmoonneellllaa rtyypphhiimmuurriitunm TTAALSOSO...................c.v.o.e.:.11B9 Table 3: PreliminaryToxicity Test in Salmonella typhimurium TAIS3S ................20 Table 4: PreliminaryToxicity Test in Salmonella typhimurium TAIS3T .............._.21 Table S: Preliminary Toxicity Test in Escherichia coli WP2 u9rA.............2.2 Table 6: Mutagenicity Test in Salmonella typhimurium TA98 Without S9...............23 Table 7: Mutagenicity Test in Salmonella typhimurium TAB With S9...........orou 24 `Table 8: Mutagenicity Test in Salmonella typhimurium TAI00 Without $9 ...........25 ``TTaabbllee 91:0:MMuuttaaggeenniicciittyyTTeesstt iinn SSaallmmoonneellllaa ttyypphhiimmuurriiuumm TTAAIISO30SWiWtihthSo9ut..S9........................2276 `Table Table 1112:: MMuuttaaggeenniiccTTiieettssyytt iinn SSaallmmoonneellllaa ttyypphhiimmuurriiuumm TTAAILSS3357 WwiitthhoSu9t..$.9.......................2289 `Table 13: Mutagenicity Test in Salmonella typhimurium TAIS37 With S9................30 `Table 14: Mutagenicity Test in Escherichia coli WP uyrA Without S9..................31 ``TTaabbllee 1165:: MMuuttaaggeenniicciittyy TTeesstt iinn ESsaclhmeornieclhliaabcpohliiWmuPr2iuum ATAWSithwiSt9h.o.u.t.S.9....................o.w.w.3n32r3 ``TTaabbllee 1178:: MMuuttaaggeenniicciittyy TTeesstt iinn SSaallmmoonneellllaa ttyypphhiimmuurriiuumm TTAAIS080WiWtihth9out..S.9............o.......o.....3345 ``TTaabbllee 2109:: MMuuttaaggeenniicciittyy TTeesstt iinn SSaallmmoonneellllaa ttyypphhiimmuurriiuumm TTAAIISO305WiWtihthSo9ut..S.9......c.................3376 TTaabbllee2221::MMuuttaaggeeaniicciittyy TTeesstt iinn SSaallmmoonneellllaa yypphhiimmuurriiuumm TTAAIISS3357 WwiitthhoSu9t.$...9.......o.rn 3398 `Table 23: Mutagenicity Test in Salmonella typhimurium TA1537 With S9..............40 Bomeme -- Study No. AAS2XK.502B0T0L1 s `Company Sanitized. Does not contain TSCA CBI aHn-2I5n1d7e0pe:nBdaecntterRiealpeRaetveArssseayMutation Test with DuPont-8867 `Table24:Mutagenicity Test in Escherichia coli WP uvrA Without $9.........vecl `Table25:Mutagenicity Test in Escherichia coll WP2 iyrA With 59... Table26:Salmonella/E. coli Mutagenicity Test ~ SummaryofResults B1...............43 Table27:Salmonella/E. coli Mutagenicity Test ~ SummaryofResults BL..............44 AERISProt smmmmenmammmmm--------l `Appendix C: Information for Japanese Regulatory AGENCIES... 59 BioReliance _ Study No. AAS2XK.502001.BTL 6 Company Saritized. Does not contain TSCA Cal - 'H-25170: Bacterial Reverse Mutation Test with an Independent Repeat Assay DuPont-8867 STUDY INFORMATION pssst) H-25170 J `SubmitsNotebookNumbers) QE ) Haske Number: 25170 `CASRegistryNumber: {SN ) `uric;(SR) KnownInpusiies{ NR) `Stability: Tchonedietsitosnusbosftatnhceesatpupdye;amroedevoibdeenscteabolfetunadebrthie was observed. Sponsor; ELduPost de NemaondCuomrpasny USA `Wilmington, Delaware 19898 `IStnuidtyiated/Completed: December05,2001/(secreportcoverpage) In-LifeInitiated/Completed: December07, 2001 / January 10, 2002 BStuodylNoe. AsAS2XK502001BTL 7 Company Santized. Does notcontain TSCA CEI H-25170: Bacterial Reverse Mutation Test with anIndependentRepeatAssay DuPont8867 SUMMARY Inde`pTheentdeesnttsRuebpsetaatnAces,saHy-u2s5i1n7g0S,awlamosnteelsltaetdiypnhtihmeurBiacutmetreisatleRrestvrearisnseTMAutSaSt,ioTnAT1e0s0t,wTiAtIhSa3nS AraoncdloTrA-LiSn3d7ucaendrdEastclhievreirch9ia.cTolhietetsetsetr swtarsapienWrPfo2rumverdAiinnttwhoepprheasseensc,euasnindgabtsheenpcleoatfe dinocsoer-proarnagteifonomretthheomdu.tTagheenfiicristtpyhtaesste.,Tthheepsreelciomnidnpahraysteox,itcihteymteustta,gewnaiscuisteydttesot,e(sitnaibtlailsahtnhde independentrepeattests), wasused 0evaluatethemutagenicpotentialofthetestsubstance. targeTtetcrealhlsydarnodfusrolaunb(ilTiHtFy )owfatshseetleescttseudbassttahneces.oTlvheentteosftcshuobiscteabnacseewdaosn scoolmupabtliebbiultitcylwoiutdhytihne tetrahydrofuran(THF)at amaximumconcentrationofapproximately200mg/mL. waIs ancthhieepvreedliumsiinnagrytaocxoinccietnyttreastt,itohnoe mfa2x0i0mmugmd/omsLeatnesdtead2wa5sp5L0p0l0atuigngpaelripqluaotte.;tThhisedtoesset s0u2bs7t1a0n1ce3w3amsg/asmoLlu.bDleobsuetlcelvoeuldstyessotleudtiwoenraet 26.070,m1g0/, m3L3,an67d, a1s0o0l,ub3l3e3a,n6d6c7l,ea1r0s0o0l,ut3i3o3n3fraonmd - to5n0i0c0ijtuygwpaesropblsaetr.vPerde.ciBpaisteatdeownatshobesfeirndviendgbseogfintnhientgoxatic6i7toytres1t0,t0 hueg pmearxpilmatuem. Ndoosaeppplreactieadbilne: themutatgestewans50i00cpgipertplayte. testIendwtehreemu1t5a,g5e0n,i1c5i0t,y5te0s0t,,1n5o0p0oasnidtiSv0e0m0utuaggpeenriplcratees.pPornesceipiwtaasteowbasesrovbesde.rTvheebdeogsiennlienvgealts 500or 1500ugperplate. Noappreciabletoxicity wasobserved. indi"cTahteertehsatu,ltusnodefrtthheeBcaocntdeirtiiaolnRseovfetrhsiessMtuutdayt,iHo-n2T5e1s7t0wdiitdhnaontcIanudespeenadpeosnittRievepemauttAasgesnaiyc responseineitherthepresenceorabsenceofAroclor-inducedrat liver 59. _ BioReliance --- Study No. AASZXK.5020B0TL1 8 `Company Sanitized. Doos not contain TSCA CBI - aHn-I2n5d1e7p0e:nBdaecntteRrieapleRaetvAesrsseayMutation Test with DuPont-8867 PURPOSE meas`uTrhiepnugirtpsobsieloitfyttiosisntduudcyerweavsertsoeemvuatlautaitontsahemsuelteacgteendilcocpiootefnsteivaelroaflstthreatinessotsfuSbasltmaonnceelblya aynpdhaimbusreinicoenofanAdraotctlohreitnrdyupctoepdhraantlloicveursSo9.fEAsccohperyiocfhtihaecporlotsotcroalinsWinPc2luwderdiinnAptpheenpdreisxBen.ce 199`7T)haensdtuOdEyCwDas(c1o9n9d8u)c.tedincompliancewiththetesting guidelinesoftheICH (1996 aod CHARACTERIZATIONOFTESTANDCONTROL SUBSTANCES "i Thetestsubstannucmeb,eHr-A25A1S7Z0,XwKa.sTrehceitveestdsbubysBtiaonRceelwiaansccheaornact0e3rDiezcedebmybtehre2S0p0o1nasnodrawsasa {26 wsahsouplrdovibdeed.stUorpeodnraetceiapmtb,iethntfesttesmpuebrsattaurnec.ewAansdeesxcpriirbateidoans of puritwya,cssotmoproesdiattiornooormottebmeprecrhaatruacrtee,ripstrioctsecttoeddeffrinoemtlhiegthetstasnudbmsotiasntcuerae.ndTthheestabilityiG, - BoifotRheleitaenscteswuobusltadnncoethrcaevievbeeceonpideestoefrtmhienseedrebpoyrttsh.e Sponsor. TheSponsorindicatedthat 109`.T9h9-e9v)e,hGicolleduLsaebdetlo,d9el.i9ve%r,Hp-u2r5c1h7a0s1e0dtfhreotmesAtlsdyrsitcehm CwhaesmtietcraalhCyodrmopfaunrayn.(TTeHsFt,sCubAsStaNnoc.e ditluetiomnspweeurnedrperraeypeatlrleuodwlirimgmheetdiatelybeforeuseanddeliveredtothe testsystem atroom [o [onli] r recom [ge] conPtorsoilstwievreceodnitlruotlesdpwliattheddicmoentcuhryrlenstullyfwoxiitdhet(hDeMmSutOa)geenxicceiptyttseosdtiaurmelaizsitdeed,bwehliocwh.wAalspdoisliuievde withwater,Allsubdividedsolutionsofpositivecontrolwerestored a-5 0 30C. $9 " Concentration We2urA (Ald2icahmChoemmiicraalCzoe.eInc.) | 10 | ExpL.oDtaNtoe.1049-1S0ep6-P2S005 CASPuNitoy . >61035-%138 BSitouRdeylNiaon.cAeAS2XK502001 BTL 9~ -- -- `Company Saniized. Does not contain TSCA CBI H-25170: Bacterial Reverse MutationTestwith an Independent Repeat Assay DuPont-8867 7 $9 " To Concentration Fr. TAL00, TAIS3S 2nitrofluorene (AldriLcohtCNhoe.m0ica7l07CHoS. Inc.) `Exp. Date 08-Mar-2006 CASPuriNtyo. 650978-%57-8 `Sodium azide (Sigma Chemical Co) BLeotDNoos. 0h98Ha016t9 `CAS No. 26628-22:8 Purity 599% Si9g-maamCinhoeamcirciadinCeo) TALS? No. 106F0668] Exp. Date 18-Nov-2004 --- `CAS No. 90-459 Purity 598% `Methyl methanesulfonate: (AldrLiochtCNhoe.m1ic5a5l2C6oA,0 Inc.) WP2uvrA Exp. Dates 08-Jan-2003 and 28-Nov-2003 CAS No. 66273 Purity 599% `mutTaogecnoincfitiyrtmetshtewsatesrpilliattyeodfotnhseteelsetctsiuvbesatagnacre,wtihtehhaingahleisqtutoettvsoulbusmtaenecqeudaolsteoltehvaetluusseeddiinntthhee test.Theseplateswereincubatedunderthesameconditionsasthetest. _ BiSotuRdeylNioa.ncAeAS2XK.502001.BTL 10 Company Sanitized. Does not contain TSCA Cal aFn-I2n51d7e0p:enBdaecntetrRieapleRaetvAesrsseaMyutation Test with DuPout.8867 MATEARNDIMAETLHOSDS ApFpoernsduiCbx.missiontoJapaneseregulatoryagencies,additionalinformation isincluded in TestSystem The TAL00, tester strains TALS3S and uTsAeIdSw3e7reats hdeeSsacrlimboendeblylaAhmpehsimuefriaul.m h(i1s9t7i5d)inaenaduxEostchreorpihcshiTaAScoSl,i d'iWrPec2tulvyfrrAoamsDdre.scBrriubceedAbmyeGsr,eUenniavenrdsitMyuorfiCeall(i1f9o7r6ni)a.,SBaelrmkoenleelylaantedsEie.rcsotlratiensstweresrterariencsewieverde recivedfromthe NationalCollectionofIndustrialandMarineBacteria,Aberdeen,Scotland. histiTdeisnteeirnsdterapiennsdTenAc9e8(aprnodtoTtAroLpShy3)7bayrferraemveesrhteidftfmruotmahgiesntsi.dTiensetdeerpsetrnadiennTcAeL(Sa3uxSoifsrroepvheyr)tteod c`abyusmeubtaogtehnstfhraatmcesahuisfetbaasnedpbaiarsseupbsatiirtsuutibosntsi.tTuetsitoenrmsuttraaitnioTnAsI.0S0piescriefviecirttyeodbfytmhuetargeevnesrtsihoant ``mecmhaniusm(tGirneEae.nactnodliMiiusrisoeeals,ni1t9i7vs6e)t.obase-pair substitutionmutations,ratherthan frameshift -- the`aOpvpreompirgihttecuflrtouzreenspweerrmeapnreenptasrteodcbkyinitnoocauvleastsienlgcfornotamitnhiengapp5r0opmriLaotefmcausltteurreplmaetdeoiurmf.roTmo `amsosnuirtetorheadt.cFuolltulroewsiwnegrineohcaurlvaetsitoend,ieancahtfelaosgkpwhaassep,ltahceeldeinngtahroefsitnicnugbsahtaikoenr/iwnacsucboanttorroallerd oaonmd atetmp3e7r4a2turCea.pTphreoxsihmaakteegl/yncu12bhaotuorrwsabesfporroegtrhaemamnetditciopbaetegditnismhaekoifnghaartvaepsptr.oExaimcahtceullytu1r2e5wrapsm `monitoredspectrophotometrically forturbidityandwasharvestedat apercenttransmittance y`viiealbdliencgouantittteesrtosfoanppnurtorxiiemaatatgealrypl10atceesl,lasnpdetrhmildlaitlaitiesr.oTnhfielaecbtuutalntoittperrsewseerneeddeinttehrimsirneepdobryt. R`eTvheesrtsuedy MwuatasctioonndTuecstte)d,toacdoompptledywJiutlhy1O9E9C7DG(upiudbelliisnheed47F1eb(rGuenaertyi1c 9To9x8i)coalnodgyw:Biatchtetrhiael InPtheamramtaicoenutailcCaolnsffoerrHeuncmeaonnUsHear(m1o99n6isaantdion19o97f). TechnicalRequirementsof Registrationof MetabolicActivation System preApraorceldofrro12m5m4a-linedSupcreadgruate-iDvaewrlSe9ywraatssuisnedduacsetdhweimtehtabaosliincgalcetiinvtartaipoenrsiytsotneeaml.iTnhjeecSti9onwoasf `<Ar7o0clCoorr1c2o5l4d,e5ru0n0timlgu/skegd,.fEiavcehdbauylskpprrieorpatroastaicorniofifce$.9Twhaest9estweadsfboarictshapbrielptayrteodamentdasbtoolriezdea2t- aminoanthracene and typhimurium TA100. 7,12-dimethylbenz(a)anthracene to forms mutagenic to Salmonella _ BioReliance --- Study No. AASZXK 502001 BTL n Company Sanitized. Does not contain TSCA CBI a'nH-I2n5d1e7p0e:nBdaecntetrRieapleRaetvAesrsseayMutation Test with DuPont-8867 `lucToshee-$6-9phomsipxhawtae,s4pmreMpaBred-imnmeidiacteloybtefioredniintuascluemsoetiiadenddphcooesnpth-aaitneae,d8d1m0eM%MagS9Ci,l,n5 maenMd c3o3ntmaiMnKinCgl1i0n0maM1p0h0osmpMhaptheobsupfhfaetreabtupffHer7a.t4, pwHas7p.r4e.pTahreediSmhmaemdSia9temliyxtbeufroer(eSthsaumsmei.xT),o confirmthe serilityofthe $9and Sham mixes,a0.5mLaliquotof cach wasplatedonselective agar. Solubility Test dimeAtshoyllubsiulliftoyxtiedset w(aDMsScoOn)d,ucettehdatnoolse(lEetcOtHt)h,evaecheitcolnee., Tahceettoensittiwlae,sctoentdrauhcytderdofuusrianng w(aTtHEe)r,, pverboipcyllee, nseelgelcytceodliannodrdpeorlyoeftphryelfeenreegnlcye,cotlh.atThpeertmeistitesdubprsetpaanrcaetwioan sotfetshteedhtigohdeesttesromliunbelteoher `swoolrvkeanbtsl.estockconcentration,upto 50mg/mLforaqueoussolveatsand 500mg/mLfororganic Preliminary Toxicity Test subs`tTahnecperewloiumlidnabreytteosxtiecdi.tyVteehsictlewaansudtseenddtooseesltaebvleilsshotfhtehedtoesset-sruabnsgteaonvceerwwerheipclhattheed,toenset: - sepllaetcetipveermdionsiem,awliatghaorvienrtnihgehptrecusletnucreesaonfdaTbAsSeBn,ceTAoIf0Ar0o,clToArI-Si3n5du,cTeAdrLaSt3l7ivaernd$W9.ED2osuelAeveolns testedwere 6.7, 10, 33, 67, 100, 333, 667, 1000, 3333andS000 ugperplate. Mutagenicity Test `mut`aTgheenmiucptoatgeenntiicailotyfttehsett(eistnsaulbsatanndcei.nSdiexpednodseenlterveeplesoatftteessttss)uwbastsaunscee(d15t,o5e0v,al1u5a0t,e5t0h0,e w1i5t0h0aTnAd9580,0T0AuIgOpOe,rpTlAaIteS)3aSl,onTgAwIiSt3h7apparnodpriWaPte2vuevhricAleainndthpeosiptrievseecnocnetraonlsdwaebrseenpcleateodf Arcoonctlroorl-siwnedruecpeldatreadtilinvterrip$li9c.atAe.lldoselevels oftestsubstance,vehiclecontanrdpoosiltisve Platingand Scoring Procedures origi`nTahleltyedsetsscyrsitbeemdbwyaAsemxepsoseetadlt.o1t9h7e5t)eastnsduubpsdtaatnecdevbiyaMtaheroplnaatneidnAcomreposra(1t9i8o3n).methodology (WIOV)n,twhaesdmaeylotefdaitnsdussuep,pmlienmiemnatletdowpiatghLa-rh,icsotndtianien,iDn-gbi0o.t8i%naangdaLr-t(rWy/pVt)opahnadns0o.l5ut%ionNtaoCla wfiintahl2co5ncmeLn.toraftwioanteorff5o0reuaMcehac1h0.0mTLopoafgmairnniomtaulsteodpwaigtahrS.9Foorr tShheaprmempiarxawtaiosnsoufpmpeldeimaenatnedd _ SBtiuodRyelNioa.ncAeAS2XK 502001.BTL 2 -- Company Sanitized.Does not contain TSCA CBI H-25170: Bacterial Reverse Mutation Test with anIndependent RepeatAssay DuPont-8867 r`eWaagteenrtsS,yasltlerme.fBeoretntceosmtaogawartwearismVpolgyestle-rBioleu,ndeerimoinniizemdalwmaetedripurmodEuc(eVdobgyetlhaenMdiBlolain-eQrR,ea1g9e56n)t containing containing 11..55%%((WW//VV))aaggaarra.nNdustuipepnltebmeonttteodmwaigtahr2w.a5s% (VWo/gVe)lBOoxnoniedrNmuitnriiemnatlBmreotdhiNuom. E 2 O(xdoryipdoNwudterri)e.ntNuBtrroitehntNoB.ro2t(hdwryaspoVwodgere)l.-Bomnersalt solution supplemented with 2.%5 (W/V) leveEla,tcehsptlerastterawians,laanbdealcetdiwviattihona,coads edseyssctriebmetdihan diedetnatiilfiiend BtihoeRetelsitasnubcset'asnSctea,ndeasrtdphOapseer,adtoinsge Procedures. testOsnubes-thaanlcfed(0i.l5u)tmiiolnlwlteerreoafd$d9eodrtSoh2a0mmmiLxo,f1m0o0lLteonfsteelsetcetrisvtertaoinpaangda2r5atu4L5o2fveCh.icAlfetoerr pvloarttienxgitnhg,etphoesmiitxitveurcoenwtraoslosv,etrhleatiedsotnstuobtshteasnucrefaalcieqoufot2w5amsLreopflmaicendibmyalbaoSttOomLaaglari.quWohteofn ianpcpurbopartieadtfe oporsiatpipvreocxoinmtarotle.lyA4ft8ertthoe7o2vbeorularyshaatds3o7l2idiCf.iePdl,tatheespltahtaetswweerreeinnovetrctoeudnatnedd ibmemecdioatenlyfd(ollelusostwichnagntt1h0eedianycdsu)b.ationperiod were storedat2-8Cuntilcolonycounting could - toxi`cTihteycboynduistiionngofa tdihsesbeaccttienrgiamlibcarcokscgorpoeu.ndPlreacwinpwitaasteevwaalsuactveadlfuosrteevdibdyenvciesoufatleesxtasmuibnsatatnicoen cwointthrooultpmlaagtenuisfiicnagtitohne.coTdoxeiscsihtoywanndbdeelgor.eeofprecipitation werescoredrelativetothevehicle [|NSoiimghauyl |[DiDsitsitnagguuiisshheeddbbyyaahneoatlitchyeambilcertohcionlnoinnygolfatwnh,emicrocalony awa|] Reancey [20dpossiblyaslight increaseinthesizeofthemicrocolonies| `Moderately |DiSinguished by amarkedthinning ofthemicrocolony Tawa] Reduced"|esating |compared intoatphreovnoeunhceicdoicnntcrlroeeaspleaiten.thesizeofthemicrocolonies Extremely |Driessutlitnignugiisnhaendbinycarenaseexitnrtehmeestihzienonfintghoefmictrhoecmoilcornoiceoslcoonmyplaraewd]| Reduced [1v0thietvsoethiihcelubencaoilndteredoelypelaasteissoulcahtetdchoalotnhieesm.icrocolonylawnis Ew greater thanorequal to90%ofthe plate. erEE re Precipitate_|to microscopictestsubstanceprecipitate. _ BioReliance --- Study No. AASZXK.5020B0T1L 13 Company Sanitized. Doss not cantain TSCA Cal 'H-25170: Bacterial Reverse Mutation Test with anlndependentRepeatADuPsoms88a67y [CodeTDescription | _________Coanctenistis | Nou-Intecfering Distinguishedby precipitate ontheplate that is visible tothe| naked eyebutanyprecipitateparticlesdetectedbythe automated| Precipitate |colonycountertotallessthan 10%oftherevertantcolonycount| (le.sstha.n3, particlesona plate with30revertants). Inerfeing Distinguishedby precipitate ontheplate that is visible tothe| | kodeye and anyprecipitateparticlesdetectedbytheautomated] resin |colonycounter exceed 10% ofthe revertant colony count (e.g. pi morethan 3particleson aplatewith30revertants). Theseplates) arecountedmanually. Revertant coloniesfora giventesterstrainandactivationcondition,exceptforpositive controls,werecountedeither entirelybyautomatedcolonycounter orentirelybyhandunless theplateexhibitedtoxicity. EvaluoaftReisuoltns Forcach replicateplating,themean and standarddeviation of the numberof revertants per `platewerecalcaundlaraeretpoertedd. - Forthetestsubstancetobeevaluatedpositive,itmustcause adose-related increaseinthe `meanrevertantsperplateof atleastonetesterstrainover aminimumoftwoincreasing `concentrationsoftestsubstance.Datasetsfortesterstrains TA1535and TA1537werejudged positiveiftheincrease inmeanrevertantsatthepeakofthedoseresponseisequaltoorgreater WtPha2nuv3.r0-Atiwmeesrtehjeumdegaend vpeoshiitcilveeciofnttrhoelivnaclrueea.sDeiatnamseetasnfroervteersttaenrtsstartaitnhseTpAe9a8k,ofTAt1h0e0daosned `response is equaltoorgreaterthan2.0-timesthemeanvehiclecontrolvalue. Crifotr aeVar lidiTeast The following criteria must bemetforthemutagenicity test to beconsideredvalid.All Salmonella testerstrainculturesmustdemonstratethepresenceofthedeeprough mutation (a) atnhde tphreedseelnecteioonfitnhtehpeKuMvIrBOgIenpel.asCmuiltdurR-efsaocftotre.stAelrlstWraPi2ns wTwAr9A8caunltdurTeAs1m0u0smtudsetmdonesmtornastteratthee d sponetanl ieonue tshrt eeuvevi rrtaAno gtsenn ine.thAellvceuhlictluerecsomnutrsotlsdeamsonfsotllroawtset(hinecclhusairvaec)t:erTiAs9tEi,cme10a-n50n;umTbAeLr0oOf, 80-240; TAIS35, 5-45; TALS37, 3-21; WP2urA, 10-60. To ensure that appropriate m0u3mxb1e0rscoelflbsa/cmtLe.rTihaeamreepalnatoefde,atecshtpeorssittriavienccounlttruorlemtuitsetresxmhiubsittabtelgeraesattaer3t.0h-afnoldoirnecqreuaasletion ttohhnreeenoeunrombnbo-ettrohoxofifcrdtehoveesrfetolalenlvteoslwosivinegrcrtroihgteuemirireaeadantrvoeaemvleautle:uo(aft1et)hteAer>ted5sap0teac.%tirAveeddvuoecshteiicolnleveieclnointsthrceoolmn.seiAadnemriennduimtmobuxeimrcooifff BioReliznce p= Study No. AAS2XK.502001.BTL 14 -- -- Company Sanitzed. Does not contain TSCA CBI = aHn-2I5n1d7e0p:enBdaecntterRieapleRaetveArssseayMutation Test with DuPont.$867 raocvceormtpaannsipeedrbpylaanteaabrsucpotdmopsaer-eddetpoentdheenmtderaopnivnethhieclreecvoenttaonlcvoaulne.,(T2h)iAsrmeodduecrtaitoenemduuscttiboen PionsitthivbeaCcokngtrrooulnVdallaewsn(ibaicnkcglurdoeudnidncAopdpeeonfdi3x,A4.or 5.AcopyoftheHistorical Negativeand Archives OpAerlatlinrgaPwrdocaead,ure aonytdhaelBliroepRolratsncweiRllAbQeAmuaiinttaeiandeqduaractceorreddiantg:tBiooRSetlanncdaer,d l1e4a5s2t0tBhrreoesycehaarrstRaofatde,wRhoicckhviillmee,tMheDS2p0o8n5s0o.rPewrilthbiseScOoPn,tapcatpeedrfeocrorddesciwsiillobnearsettaoitnhedefofirnaal dciosppoiseidtaionndtohft.hceompaytewriialllsb.eArleltasitnueddyimanttehreiaBlisorReetluirnaendcteoatrhcehiSvpeosnsfooroarmdienstirmouyemdowfil1l0fyiesatrbse, reUsniudsueadldtoestisnugbssotlauntcieownislwlebreddiissppoosseedodofffoflollolwoiwnignfginaaldimziantiisoniraoiftohne 0retphoret.tet systemandall Deviations ofthiNsosktnuodywndeviationsfrom theprotocolor ssay-methodSOPsoccuredduringtheconduct BSitouRdyelNaon.ceAAS2XKS02001BTL 1s-- -- Company Saiz. Doss not contain TSCA GBI aHn-I2n5d1e7p0e:ndBeanctteRrieapleRaetvAesrssaeyMutation Test with DuPont $867 RESANUDDILSCUTSSISON Solubility Test. targ`eTtecterlalbsyacraodfsuorlaunb(iTlHitFy)owfatshseetleescttseudbassttahncees.olTvheentteosftcshuobiscteabnacseewdoasnscoolmupabtliebbiultitcylwoiutdhytihen: tetrahydrofuran(THF)at amaximumconcentrationof approximately200mg/mL. PreliminaryToxicity Test wer"eTgheenreersaulttesdionfEtxhpeeprrielmiemnitnAaLry.tIonxtichietpyrteelsitmairnaerpyrteosxeinctietdytiensTtatbhleemsa1xtihmruoumgdho5s.eTthesetseeddwaatsa p5l0a0t0inugaglpieqrupotl.aTthe;ettehsitssduobssetwanacseawcahsiaesvoelduubslienbgutaccloonucdenytsroaluttiioonnoaft220000mmgg//mmLLaannddasao2l5ubplLe.: andclearsolution from 0.27 to 133 mg/mL. Dose 667, 1000,3333andS000 ugperplate.Precipitate lweavseolsbsteesrtveeddwbeergein6n.i7n,g1a0,t6373,o6r7,101000u,g3p3e3r, `plmaatex.iNmuomadpopsreepcliaatbeldeitnotxhiceimtyutwaagsenoibcsietyrvteesdt.wBaass5e0d0o0nutghpeerfipnladtien.gsofthetoxicity test,the - Mutagenicity Test `Tab`lTehs2er6esaulntds 2o7ft.hTehmeusteagdeantiacwiteyrteegsetnareeraptreedsienatEexdipnerTiambelnetss6Bt1hraonudghB2.5 aDnodsseulmemvaelrsitzeesdtiend o`rwer1e51050,u5g0p,e1r5p0l,a5t0e.0N,o1a5p0p0reacnidablSe0t0o0xiucgiptyewrpalsaoteb.sePrrevceidp.itatewasobservedbeginningat500 In Experiment BI observedwithany ofth t(eIsntiteirasltraMutaigenniitchietrythTeesptr),sennocepoorsaibtisveencmeuotfagSe9naicctirveastpioonn.ses were. `obsIenrvEexd pweirtihamennytofBth2e(tiensdteerpetrnadiennsit nReeptehearttTheesptr)e,sennocepoosriatbisveenmcuetoafgSe9naicctirveastpioonns.es were CONCLUSION BacAtelrliaclriRteevreiarfsoerMuatvaatliiodnsTteusdty wwietrheamneItndaespdeensdcernitbReedipenatthAespsraotyoicnodli.caTlheethraets,uultnsdoefr tthhee. ``cpornedsietnicoeonsroafbtsheincsseolfyA,rHo-c25l1o70rd-idirnnaotdtlciuavecurseSe9d.apositivemutagenicresponseincither the --- BioReliance Study No. AASZXK.502001 BTL 16 -- -- `CompanySanitized. Doesnotcontain TSCA CBI - H-25170; BacterialReverse Mutation Testwith an Independent Repeat Assay DuPont8867 REFERENCES AmesM,utaBgNe,ns J.wMitchCatnhenaSnadlmEo.nYelalmaaMsaamkmial(i1a9n75)MMiectrohsoodmsefoMruDteatgeecnticiintgyCarTcesitn,ogMeuntsaatinodn Research,31:347-364. GreeMnu,tMa.tiHo.nLR.easnedarWc.hJ3,8M:u3-r3i2.l(1976)Matagentestingusingtrp+reversion inEscherichiacol, InteomfatPihoanramlaCcoenufteirceanlcsefoonrHHarummonainsaUtsieo.n(GIuCiHd)aonfceTeocnhnSipcaelcRiefqiuciArsepmeencttssfoofr RReeggiusltraattoiroyn o`fGetnhoetoIriCcHitpyTresotscofnoersJPuhlsayrm1a9c,e1u9t9i5c,aFlesd.eSr2aAldReogciusmteern6t1re:c1o8m1m9e8n-de1d8f2oA0prra2id,lop2t4i,o1n9a9t6s.cp 4 InteomfaPthiaornmaalcCeountfiecreanlcsfeoornHHaurmmaonnUissaet.ioGne(nIoCtoHx)iociftTye:chAniSctaalnRdeaqrduiBraetmteenrtysffoorrGReengoitsotxraitciiotny pTreoscteisnsgoonfPJhualryma1c6,eu1t9i9c7a.lFse.dSe2raBldRoecgiusmteenrt6r2e:1c6o0m2m6e-n1d6e03d0f,oNroadvoepmtbieorna2t1s,t1e9p974.oftheICH - Maron, DM. Mutation and BN, Research, Ames (1983) 113:173.215. Revised Methods for the Salmonella Mutagenicity Test, `OE1C0DtGhueidOeElCinDeGu4i7d1el(GienneestfiocrTtohxeiTceolsotgiyn:g BoafcCtheermiailcRaelvse,prusbelMiusthaetdibonyTOesEsC)D,N,iPnartihsA,dFdeebrnudaurmy 1998. `Vog`ePlr,opHeJrt.iaesn,dJ.DBMio.l.BCohnenme.r,2(1189:596)7-A1c0e6.tslomithionafsEe. coi: Partial PurificationandSome _ BioReliance StudyNo. AAS2XK.5020B0TL1 1" -- Company Sanitized. Dogs not cantain TSCA CBI 'H-25170: Bacterial Reverse Mutation Test with a t Assay DuPont-8867 PBraecltiemriinaalryMuTtoaxticiiotnyTTeesstt Table 1 STtesutdysuNbusmtbanecre 14:: AEA-S2I5X1K70.S02001.8TL StBrpoariinzent No. :: AmLss VDeahtieclPelated: t7etDercahy2d00r1ofuran Plating Aliquot : 25 ul. TCeosntcensturbasttiaonnce RevWeirtthan$t9s ActBiavcaktgiroonund bg per plate per plate Lawn Vehicle 1 1 RWeivtehrotuetnc5s9 AcBtaicvkagrtoiuonnd por plate Lawn 2 1 160.7 95 11 25 11 3&3 1100 1we 1122 1we -- 130303 567 1197 mmpe 12 we 16s wwee 5 me 10330303 1160 mmpe 110 mwee 5000 10 me 13 ne BackgroLusnNdormLaalw;n C2o-dSelightly reduced; JsModerately reduced 4NPxeENxotnr-eImnatleyrfreerdiuncegd;preSc-iApbisteantte;; G=IOpb=sIcnutrerefdebriyngprepcriepciitpaitteate -Bi--oReliance Study No. AAS2XK.502001.BTL 18 `Company Sanitized. Does not conTtSaCAiCBnI 'H-25170: Bacterial Reverse Mutation Test with o DuPont. 8867 PrBealcitmeriinaalryMTuotxaitciiotnyTTeesstt Table 2 TeSsttudySuNbusmtbaenrce 1d:: AHA-S2Z5X1K7.0S02001.8TL StExrpaeirniment No. :: ATlai00 VDeahtieclPelated : 7teDtercany2a0r01oturan Plating Aliquot : 25 ul CTeosntcenSturbasttainocne RevWeirtthan5t9s AcBtiavcaktjiroonwnd 1g per plate x plate Lawn Vehicle 148 1 RWeivtehrotuatnts59 AcBtaicvkagtrioounnd x plate Lawn 120 1 160.7 101221 11 11502 11 3@ 113a4 1me 115309 1we 130303 s6 116470 mmee 136 we 113328 mwee 123 we i 13030303 112143 mmep 115217 mwee 5000 105 me 12 we BackgroLuenNdormLaalw;n C2o=dSelightly reduced; Jekoderately reduced Ndp=eENxotnr-eImnetleyrrfeedruicnegd;preSceiApbisteantte;; 6=IOPbasIcnutrerefdebryingprperceicpiiptiattaete BiorRelirance. `Study No. AAS2XK502001BTL -- 19 `Company Sanilized. Does not contain TSCA CBI H-25170: Bacterial Reverse Mutation Test with an Independent Repeat Assay DuPont8867 PBraecltiemriinaalryMuTtoaxtiicointyTTesetst Table 3 TeSsttudSyubNsutbaenrce 18:i AH-A2S5Z1X7K0.502001.5TL stBerpaeirninent No. i aALsi VDeahtieclPelated:5 7teDtercahy20d0r1ofuran Plating Aliquot : 25 ub CTeosntcensturbasttiaonnce RevWeirttahnt5s9 ActBiavcaktgiroonund x plate + plate Lawn Venicle 17 1 RWeivtehrotuatnt5s9 AcBtaicvkagrtoiuonnd plate Lawn 12 1 59.)7 33 7s 11 1 i 012 11 10 1 1o00 333 1126 nnee 1 we 153 wwee 1 we -- 1066070 113 wwee 1113 wnee 3333 3 we 1 me --S Bac0 kgr0 o1uenNodrmLaalw;n C2o=dSelight1l2y aw 0 19 reduced; IsModerately reduced 0 awe N4e==ENxotnr-eImnetleyrfreerduicnegd;pre5c=iApbistenatt;e; GI=POablscnutreerdfebryingprperceicpiiptiattaete DBiR oReliance miaeme-------- i---------- _ Study No. AAS2XK 502001BTL 2 `Company Sanitized. Does notconTtSaCAiCBnI a'oH-25170: Bactetrial ReAvserssaeyMutation Test with DuPont $867 PBraecltienriinaalryMTuotxaitciiotnyTeTsetst Table TeSsttudySuNbusmtbaenrce Id:i HA-A2S5Z1X7K0.502001.TL StBroeariinnent No. 1i AmLis VDeahtieclPelated i: t7ecDercahy20a0r1ofuran Plating Aliquot : 25 pL TCeosntcenSturbasttainocne RevWeircthan5t9s ActBiavcaktgiroonusd RWeivtehrotuatnts55 AcBtaicvkagtrioounnd ug per plate Vehicle per plate Lawn 1 per plate Lawn s 1 160.7 33 75 11 5 1 55 11 3 1 1&00 333 se awee 2 we 7s wwee 3 we --- 1056070 `3 wwee `5 wwee 50330303 58 wwep 3s awwee Backgro1u=nNodrmLaalw;n C2o=dSel.ightly reduced; I-Moderately reduced N4P=-ENxotnr-eInnetleyrfreerduicnegd;preSceiApbisteantte;; G-IOPbsaIcnutreerfdebriyngprperceicpiiptiattaete BioR-- elianc-- e -- Study No. AAS2XK502001.BTL 21 `CompanySanitized. Dosnot contain TSCA Cal H-25170; Bacterial Reverse Mutation Test with a t DuPont8867 PrBealcitmeriinaalryMuTtoaxticiiotnyTeTsetst Table 5 STtesutdySNuubsmtbaenrce 14:: HA-A2S521X7K0.502001.BTL StExrpaeirniment No. :LoAwle wen VDeahtieclPelated 7teDtercah2y0d0r1ofuran Plating Aliquot : 25 ul TCeosntcensturbasttainocne RevWeirtthan5t9s ActBiavcaktgiroonund _ugperplate Vehicle porplate 16 L1awn RWeivtehrotuatnt5s9 Activation Background perpl1ate L1awn 160.7 11 11 1102 11 3a3 1102 w1 e 18 11 130303 312 wwee 165 wmee -- 1056070 1160 wwee 112 wwee 35030303 105 wmee 110 winee Backgr-ouNnodrmLaalw;n C2o-d5elightly reduced; 3=Moderately reduced N4P=E-xotnr-eImnetleyrfreerduicnegd;preSc=iApbisteantte;; 6I-pC=hIsncutreerdfebryinpgrperceicpiiptiattaete oR StudyNo. AAS2XK 502001 BTL 2 Company Sanitized. Doesnotcontain TSCA CBI 'H-25170: Bacterial Reverse MutationTest with a Assay 'DuPont-8867 Bacterial Mutation Test Table 6 TSotsutdySuNbusmtbaernce 1d:: HA-A2S5I1X7K0.502001.BTL Experiment No : BL sLtirvaeirnMicrosones +: mNoense CDealtlesPlSaeteedded :: 21.94DeXc102001 VPelahtiincgle Aliquot +: t25etrahydrofuran C1gonpceerntprlaattieon NPulmabteer Rpoerverptlaanttes BacCkogdreound RAevveerratgaents DSetvainadtairodn Venicle 0021 1100 11 03 10 1 0 15 002 112 11 03 12 1 15 1 s0 o012 1100 11 03 10 1 10 o - 150 002 15 11 0 10 1 10 2 500 o021 1120 wnee 03 5 we 10 2 1500 0o21 1100 wwee 03 16 we 12 3 5000 o00312 n1u28 wwweee un 2 Positive Control o2-1nitrofluor1e5n7e 1.0 yg1 per plate 02 78 1 --Ba_c--kground Lawn Code 36 3 ws on 41=eENoxrtmraelm;el2y=rSeldiugchetdl;y Sr-eAdbusceendt;; Is6M=oOdbesrcautreeldybyrepdruecceidpitate NPeNon-Interfering precipitate; IPaInterfering precipitate BioReliance StudyNo. AAS2XK.502B00T1L 2 Company Sanitized. Doosnotcontain TSCA CBI 'H-25170; Bacterial Reverse Mutation Test with = Assay DuPont-8867 Bacterial Mutation Test Table 7 STetsutd.ysuNbusmtbaernce 1d:+ AH-A2S521X7K0.502001.BTL Experiment No : BI StLirvaeirnMicrosomes +: mRastsliver S9 DCealtlesPSleateedded :: 125.4DXec102001 VPelhaitcilneg Aliquot :+ 2t5eturoahydrofuran uCeoncentraltaiteon NPulmabteer pRoervertplaanttes BacCkogdreound _RAevveerratgaents SDteavnidaatridon Vehicle 0012 1160 11 0 21 16 7 15 0012 11 11 0 13 1 15 2 50 0012 112 11 03 18 1 16 3 - 150 o021 110 11 0 11 1 1 500 o012 120 awvee 03 12 we 15 1500 0012 11 wwee 0 15 we 1 1 5000 o02 1n6 mwee 03 1 we 1 2 Positive Control 2o-1amincanth4r6a7cens 1.01ug per plate 0023 6028 11 rr 3 Backgro1u-nNdormLaalw;n C2o-dSelightly reduced; J=oderately reduced N4p=eBtxotnr-eImnetleyrfreerdiucnegd;preSc=iApbisteantt;e; 6I=PO=bIscnutreerdfebryinpgrepcriepciitpaitteate BioReliance _ Study No. AAS2XK502001 BTL % Company Sanitized. Does not contain TSCA CBI H-25170: Bacterial Reverse Mutation Test with Py Assay DuPont-8867 Bacterial Mutation Test Table 8 Test Substance Id: H-25170 stStruadiynNumber : TAAALS020XK.502001.BTL CEexlplesrimSeenetdeNdo : : BL 4.1 X 10% vLeihviecrleMicrosomes : Ntoenterahydrofuran Date Plated : 19 Dec 2001 Plating Aliquot : 25 yl Concentration ug per plate Plate Number Revertants per plate Background Code Average Revertants Standard Deviation vehicle 01 160 1 o03z 15604 1 1 159 5 15 0 187 1 0023 115401 1 1 159 2 50 0021 161420 11 03 48 1 150 n - 150 or 146 1 o0z 112484 1 1 139 10 500 002 156 133 we we 0 161 we 143 12 1500 0021 68 151 we we 0 15 we 124 5000 o0z1 119533 mmee 0 153 we 166 2 Positive Control so01dium azid4e911.0 ug pe1r plate --_-- 8 0023 6 550136 3 11 s5s 03 0on13 Backgro1u-nNodrmLaalw;n 2Co=dSelightly reduced; 3eModerately reduced NEPx-tlNroenm-eInltyerrfeedruicnegd;preSc=iApbisteantte;; 6I=POsbIsnctuerrefderbiyngprperceicpiiptiattaete BiRoRebliance _ Study No. AAS2XK502001 BTL 2 Company Sanitized. Does not contain TSCA CBI H-25170: Bacterial Reverse Mutation Test with a Assay DuPont:8867 Bacterial Mutation Test Table 5 TSetsutd.ysNuubmsbtearnce 1a:|: AB-M2S5I1X7K0.S0001.TL Biperiment No : BL Lsitvraetr Microsones + 1Ra0t 0liver 59 Vehicle tetrahydrofuran CDoaltelePSleaedceedd:: 419.1Dec102001 Plating Aliquot : 25 ul Concexntrapltaitoen NPulmabteer Revertlaatnet's BacCkogdreound RAevveerratgaents SDetvainadtairodn Venicle aa2 113663 11 a 191 1 163 2 15 o0n 118605 11 0 167 1 m s 50 o02 16 11 0 160 1 151 2 - 150 a02 162305 i1 03 165 1 189 s00 0o 118513 wwee 0 16 we 166 1 1500 0on 181573 wwee 0 me 176 2 s000 o0r 1m9n6 mwee 0 165 we wr 16 Positive Control 2o-raminoanthr7a63cene 1.0+ug per plate 20 s2s 1i es 126 Backgro1euNnodrmLaalv;a C2osdSe1ightly eBxtrenely reduced; SreeAdbuvceendt;; 3G=xNOobdaecruarteedlybyrepdruecceidpitate Neston:Interfering precipitate; P-Interfering precipitate _ StBiuodRyelNioa.ncAeASZXK502001 BTL 2 Company Saritized. Doesnot contTSaCAiCBnI 'H-25170; Bacterial Reverse Mutation Test with o t DuPont-8867 Bacterial Mutation Test Table 10 TSetsutdysNuubmsbtearnce 1d: HA-A2S5Z1X7K0.502001.BTL Experiment No : Bl LsitvrearinMicrosomes :+ NTAoLnSe3S DCaotlelsPSleaedteedd:: 125.7DeXc102001 vehicle : tetrahydrofuran E eConE e centrm atN iom n m PLlaItm eE m Revere tantm s Br ackge rounr d Ae verae ge gSte andae rd -- or plate Number per plate Code Revertants Deviation Vehicle 0012 11s2 11 03 31 15 2 15 o00a32 1r108t 111 1 50 0021 1102 11 -- 0 12 1 n 1 150 002 115u 11 03 u1 12 2 500 0021 1100 wwee 0 8 ee s 1 1500 o012 1102 wwee 03 12 we u 1 5000 0021 112 mmee 03 13 we Bn 1 Positive Control so01dium azi2de971.0 ug pe1r plate 0032 233102 11 260 a Backgro1u-nNodrmLaalw;n C2o-dSelightly reduced; I=Moderately reduced NdPseENxotnr-aImnetleyrrfeedruicnegd;preSciApbisteantte;; =IOpbssIcnutreerdfebryinpgrperceicpiiptiattaete BioReliance StudyNo. AAS2XK502001 BTL 27 Company Sanitized. Does not contain TSCA CBI H-25170; Bacterial Reverse Mutation Test with a Assay DuPont-8867 Bacterial Mutation Test Table 11 TSetsutdysWuubrsbtearnce Id:: AHA-S2Z5I1K7.0S0J00L.BTL Experiment No : BL stLrivaeirnMicrosomes :+ RTaatIS3lsiver 59 DCoaltleaPSleateedded :: 129.7Dexc102001 VPleahtiicnlge Aliquot :: 2t5eturlahyarofuran Cugopnceerntrapltaitoen NPulmabteer Revperertplaanttes BackCogdreound RAevveerratgaents DSetvainadtairodn Venicle 0021 55 11 0 31 10 2 15 002 125 11 0 10 1 10 2 0 0021 15 11 --- 03 12 1 12 3 150 012 125 11 0 51 s s 00 002 2100 mmee 03 1s ee 16 3 1500 0021 u5 mmpe 0 5 we s 3 000 0o2u 1s mwee 03 12 we 10 5 Positive Control o2-1aminoant1hr2a1cene 1.01ug per plate 0032 1285 11 mn 2 Backgro1u-nNodrmLaalw;n C2o-dSelightly d=Extrenely reduced; rSe=dAubcseedn;t; 3=6MeoOdbescruarteedlybyrepdruecceidpitate NPeNon-Interfering precipitate; IPsInterfering precipitate BioReliance StudyNo. AAS2XK.502B0T0L1 2 `CompanySanitized. Doesnot contain TSCA CBI H-25170; BacterialReverseMutation Test with m Assay 'DuPont-8867 Bacterial Mutation Test Table 12 TSetsutdySNuubrsbtearnce 14:+ HA-A2S521X7K0.S02001.BTL Experiment No : BL stLirvaeirnMicrosomes : NTMoinse y DCealtlesPSleaetdeded :: 119.6DeXc102001 VPelhaitcilneg Aliquot :+ 2t5etwruanyaroturan uCgoncenpertrapltaitoen NPulmabteer Revperertplaanttes BacCkogdreound RAevveerratgaents DSetvainadtaridon Vehicle 0021 s2 11 0 s1 ` 2 15 0021 25 11 0 `1 ` 2 s0 002 38 11 - 03 s1 5 3 150 002 53 11 0 31 . 2 500 0012 `5 wwee 03 6 we 5 1 1500 0012 87 wmee 0 ` we 6 2 sa00 002 53 wwee 0 5 we 5 2 Positive Control S-01aminoacrid5i05ne 75 ug1per plate 002 8o7s 21 602 126 Backgro1u-nNodrmLaalw;n C2o-dSelightly reduced; J=Noderately reduced 4NPeeBNxotnr-eImnetleyrfreerduicnegd;preSceiApbisteantte;; 6=IOPb-sIcnutreerfdebryinpgrperceicpiiptiattaete B-i--oReliance _ StudyNo. AAS2XK.5020B0TL1 29 `CompanySanitized. Doesnot contain TSCACBI H-25170; Bacterial Reverse Mutation Test with an at Assay DuPont-8867 Bacterial Mutation Test Table 13 TSetsutdySWuubmsbtearnce Id:: KM-S225X1K7.0S02001.BTL Experiment No : BL stLriavienr Microsomes :+ Rmaatsal?iver 9 DCealtlesPSleaedteedd:: 119.6DeXc102001 VePlhaitcilneg Aliquot : t25eturiahydrofuran uCgonpceerntrpalattieon NPulmabteer pReerveprltaatntes BacCkogdreound RAevveerratgaents DSetvainadtairodn Vehicle o012 53 11 03 51 5 3 15 0021 125 11 03 71 a 3 50 0012 `5 11 --- 03 51 s 1 150 002 105 11 0 51 7 3 500 002 s$ wwee 03 5 we 5 2 1500 o012 0 55 wwee 2 me 6 1 5000 0012 55 mmee 0 5 we 5 2 Positive Control 2o-1amincant1hr0a0cene 1.01jg per plate 0I2 9866 11 5 8 Backgr1oeuNnodrmLaalw;n C2o-dSelightly reduced; 3=Noderately reduced Ne4a=Elxotnr-eImnetleyrfreerduicnegd;preSceiApbisteantte;; G=IOpb=sIcnutreerdfobriyngprperceicpiiptiattaete -B_i--oReliance Study No. AAS2XK502001 BTL 30 `Company Sanitized. Doesnotcontain TSCA C81 aHn-I2n5d1e7p0e:nBdaecntteRrieapleRaetvAesrssaeyMutaTtesitwoitnh DuPont-8867 Bacterial Mutation Test Table 14 TSetsutdySNuubssbtearnce 14:: ABA-S2O5X1K70.S02001.BTL Experiment No : BL stLirvaeirnMicrosomes :: WNozneuven DCealtlesPSleaetdeded :: 1191.2DecX 120001 VPelahtiincgle Aliquos :: 2c5ecryainyasoturan uCgonpceerntprlaattieon NPulmabteer pRoerverptlaanttes BacCkogdreound RAevveerrtaagnets DSetvainadtairodn Vehicle 0021 105 11 03 31 5 3 15 o02 1100 11 03 10 1 10 o 50 o02 1122 11 03 12 1 12 o 150 002 irnl 11 0 12 1 5 1 500 o0n2 112 wwee 03 12 we 2 o 1500 0o12 1105 wwee 03 15 me 12 2 s000 0o21 11" mmee 03 be] we 1 3 Positive Control me0thyl met1ha1n3esulfonat1e 1000 ug per plate -- o0o023 0m97% 3 11 sess a 18 Backgro1u=nNdormLaalw;n 2Co=dSelightly reduced; JModerately reduced N4P=-BNxotnr-eImnetlery freerdiuncged;preSceiApbisteantte;; GI=PO-bIsnctuerrefdebriyngprepcriepciitpaitteate BioReliance Study No. AAS2XK.502001.BTL 3 Company Sanitized. Doss not contain TSCA Cal 'H-25170:BacterialReverse MutationTestwith a atAssay `DuPont-8867 Bacterial Mutation Test Table 15 TSetsutdysNuubmsbtearnce Id:: HA-A2S5I1X7X0.502001.3TL StLirvaeirnMicrosomes : WRea2t luvievner 59 Venicle + tetranyarofuran ECexlplesriSmeeendtedNo :: B1L1.2 X 10 Date Plated : 19 Dec 2001 Cbgoncenpertrpalattieon Vehicle NPulmabteer Revperertpalanttes BacCkogdreoun_d ReAvveerrtaagnets DSetvainadtairodn 00012 111006 111 12 3 15 o0a2 12 11 03 10 1 n 1 0 002 1u0n 11 - 03 10 1 10 1 150 0012 1100 11 03 10 1 10 500 0012 u1 mwee 03 1B we 3 2 1500 002 105 wmee 03 Bn me 5 ` 5000 o012 n1w wwee 03 1 we 15 2 Positive Control 2-oa1minoanthr7a13cens 10 y1g per plate 0032 a4230 11 sis mn BackgroLueNnodrmLaalw;n C2o-dSelightly reduced; J=Moderately reduced Np4e=Etxotnr-eImnetleyrfreerduicnegd;preSceiApbistenatt;e; 6I=pO=bIsnctuerrefderbiyngprapcriepciitpaitteate BioReliance _ Study No. AAS2XK.5020B0T1L 2 CompanySanitized. Doesnotcontain TSCA CBI F-25170: Bacterial Reverse Mutation Test with am Assa DuPont:8867 Bacterial Mutation Test Table 16 TSetsutdySNuubrsbtearnce 1d:: AHS-2I5N1K7.0502001.BTL sLtirvaeirnMicrosomes :+ mNosnse vehicle + tetrahyaroturan CEexlpleariSmeenetdeNod:: 2B2.7 X 10 Date Plated: 4 Jan 2002 uCgonpcoerntrapltaitoen Vehicle NPulsahteer Revperertplaanttes bacCkogdreound o0r2 21 11 03 1s : RAovveerratgaents DSetvainadtairodn 1 . 1 002 15 11 03 20 1 16 5 --- 0 0012 17 1i 03 5: 12 s 150 o02n 105 11 03 10 1 1 1 soo o0r 1u0 zwpe 0 s axe 12 s 1500 o0n 2s wnpp 0 5 we s 3 s000 002 n` 1ipe 0 5 fe 5 3 Positive Control o2-1nitrofluor2e67ns 1.0 ug1 per plate 0032 2289 1i a3 20 BackgrIonuNnodrnLaalw;n C2o-dSe1ightly reduced; IsModerately reduced NAe=exNtorne-nIenltyerfraerdiuncegd;preSceiApbiateantt;e; GIOPbsaIcnutreerdfobryinpgrperceicpiiptiattaete _ SBtiuodRyelNioa.nceAASZXK.5020B0T1L 3 `CompanySanitized. Does not contain TSCA Cal 'H-25170: Bacterial Reverse Mutation Test with an In Assay DuPont-8867 Bacterial Mutation Test Table 17 TSetsutdysNuubmsbtearnce Td:: AA-S2I5X1K70.502001.BTL Experiment No : 52 stLrivaeirn Microsomes +: TRaa%t8liver 9 CDealtlesPSleaetdeedd :: 24.J7anX 120002 VPleahtiincgle Aliquot :+ 2t5eturiahydrofuran Cbogncpeenrtrpaltaiteon NPulmabteer pReovrerptlaanttes BacCkogdreound _RAevveerracgaents DSteavnidaatridon Venicle 0012 22 11 03 25 1 2 2 15 o02 218 11 03 18 1 i) 5 50 0o2 2203 11 -- 03 26 1 2 3 150 0021 1250 11 03 15 1 n 3 500 0o2 1n6 wwee 0 26 we 20 6 1500 0021 216 1r1e2 0 25 112 2 7 5000 0o21 1n6u wree 03 2 re 1 ` Positive Control 2-01aninoanth10r1a1cens 1.01ug per plate 0032 1096765 11 101 36 Backgr1oeuNnodrmLaalw;n C2o-dSelightly 4=Extremely reduced; rS=eAdbusceendt:; 3s6M=oOdbesrcuarteedlybyrepdruecceidpitate NPaNon-Interfering precipitate; IpsInterfering precipitate BioReliance Study No. AAS2XK502001 BTL 34 `Company Sanitized. Does not contTaSiCnA CEI 'H-25170: Bacterial Reverse Mutation Test with a Assay DuPont-8867 Bacterial Mutation Test Table 18 TSetsutdySNuubmsbtearnce Id:: HA-A2S5Z1X7K0.50J001.BTL Experiment No : 82 stLirvaeirnMicrosomes:+ TNTMoAn1e00 CDealtlesPSleaetedded :: 14.1JaXn 120002 VePlhaiticnlge Aliquot : c25eturbanyarofuran C9oncpeerntprlaattieon NPulmabteer pReerveprltaatnets bacCkogdreound _RAevveerratgaents Standard Deviation Vehicle o012 12971 11 03 17 1 196 2 1s a02 118828 11 0 15 1 182 7 s0 0021 118866 11 -- 03 200 1 150 5 150 0012 116500 11 03 197 1 180 n 500 002 1a63 wwee 0 163 we 180 2 1500 o012 127185 mmee 03 176 we 150 22 5000 0021 118813 wwee 03 195 we 186 5 Positive Control s0o1dium azide7601.0 ug pe1r plate 002 77755 11 am 5 Backgr1ouenodrmLaalw;n C2o-dSelightly reduced; J=Koderately reduced NdP=eExotnr-eImnetleyrfreerdiuncegd;preSc=iApbisteantte;; 6=IOPbasIcnutrerefdebriyngprperceicpiiptiattaete BioReliance _ Study No. AAS2XK.502001.BTL 35 Company Sanitized. Does not contain TSCA CBI H-25170: Bacterial Reverse Mutation Test with `anIndependent Assa DuPont-8867 Bacterial Mutation Test Table 15 TSetsutdysNuubmsbtearnce Id: HA-N2S5I1X7X0.S02001.BTL Experiment No : B2 SLtirvaeirnMicrosomes :+ RAa2t00liver S9 CDaetlelsPSleaedteedd:: 41.J1aXn 210002 VPleahtiicnlge Aliquot :: 2t5etpriahydrofuran Concentration ug per plate NPulmabteer Rpeerverptlaanttes BackCgodraound RAevveerratgaents DSetvainadtairodn Vehicle 0021 126030 11 03 199 1 108 2n 15 002 128050 11 5 183 1 191 12 50 oo1z 116726 11 --- 03 208 1 189 wv 150 0021 115612 11 03 165 1 159 7 500 0021 1219 wmee 03 166 1 189 29 1500 0012 11993 wmee 03 166 we 185 n 5000 0o2 181592 mmee 0 200 we 195 5 Positive Control o2-1aminoanthr5a07cene 1.01ug per plate 02 1002 1 --Bac-- kground Lawn C9 ode ee 1 ss ss i4e=NEoxrtmraelm;ely2-Sreldiugchetdl;y Sre=dAubcseedn;t; IGseMOobdsecrautreeldybyrepdruecceidpitate NPeNon-Interfering precipitate; IPsInterfering precipitate _ BioReliance. StudyNo. AAS2XK.502001.BTL 36 `Company Sanitized. Does not contain TSCA CBI aHm-25170; BactetRrieapleRaetveArsssaeyMutation Test with DuPont-8867 Bacterial Mutation Test Table 20 TSetsutdysNuubmsbtearnce 1d: AHM-2S521K7K0.SO00LBTL Experiment No : B2 sLitvrearinMicrosomes +: TNaoLnse3s CDealtelsPSleaotedded :: 24.6JaXn 120002 vePlhaciicngle Aliquot : 2t5etraubhydrofuran Cuogncenpertrapltaitoen NPulmabteer Revporertplaanttee BackCgordoeund RAevveerratgaents DSetvainadtaridon Vehicle o0n 1188 1i 03 11 1 1 o0 1200 11 11 1 ` s0 a02 22 :i --- 0 1s I 20 ` 150 0a2 112 11 03 11 1s ` 500 002 220 wmee o 23 2 1500 a2 p1e 1wpe o 1 we 16 3 5000 00 116 11px 0 1 im 16 2 Positive Control so0dium azide"201.0 uy pe1r plate o032 w08e 11 ar a BackgroIunnodrmLaalw;n c2o-tSelightly -Bxtremaly reduced; reduced-- ; IoModesately reduced SeAbaent; GeObacurad by precipitate NP-Non-Intarfering precipitate; 1PeInterfering precipitate _ SBtiuodReylNioa.ncAeAS2XK502001 BTL 3 -- Company Sanitized. Does notcontain TSCA CBI H-25170; Bacterial Reverse Mutation Test with an Independent Repeat Assay 'DuPont-8867 Bacterial Mutation Test Table 21 TSetsutdysNuubmsbtearnce Ia:: AHA-S2I5X17K0.502001.BTL Experiment No : B2 StLrivaeirn Microsomes :+ RTAaItS3lSi.ver 59 Vehicle tetrahydrofuran DCealtlesPlSaeteedded :: 24.6JanX 120002 Plating Aliquot : 25 wb Cugonpceenrtprlaattieon NPulmabteer pReerverptlaanttes BacCkogdreound RAevveerratgaents DSetvainadtairodn Vehicle 0o21 112 11 03 i) 1 15 3 1 0012 119 11 03 n1 1m 3 s0 0o2 1260 11 -- 0 n1 16 5 150 002 113 11 03 10 1 12 2 s00 002 205 wwee 03 1 we 1 6 1500 0021 1185 1w1e2 03 15 we 16 2 5000 002 1Bs 11pp 0 un re 10 Positive Control o2-1aminoant1hr6a8cene 1.02pg per plate -- 9 0032 115m%83 1 11 a1666 88 BackgroLusnNodrmLaalw;n C2o=dSel.ightly d=Extremely reduced; rSe-dAubcseedn;t; IsGM=oOdbesrcuarteedlybyrepdruecceidpitate -_-- NPslon-Interfering precipitate; IpaInterfering precipitate BioReliance Study No. AAS2XK 502001 BTL 38 Company Sanitized. Dos notcontTSaCAiCBnI H-25170; Bacterial Reverse Mutation Test with a Assay DuPont-8867 Bacterial Mutation Test Table 22 TSetsutdySNuubmsbtearnce Id:: HA-A2S5I1X7X0.S02001.BTL Experiment No : B2 StLirvaeirnMicrosones : mNao1nse37 DCoaltlesPSleaetdeded :: 41.3JanX 210002 VPelhatiicnlge Aliquot :+ 2t5etranyarofuran Concenxtrapltaitoen PNulmabteer peRervertplaanttes BacCkogdreound _RAevveerratgaents DSetvainadtairodn Vehicle 0021 s5 11 0 51 5 2 15 002 75 11 03 51 5 1 s0 0o21 103 11 -- 0 81 7 150 0on 105 11 03 :1 6 3 500 002 57 uizpe 03 3 we 5 2 1500 0o21 Is awree 03 1 6 3 5000 002 33 rwee 03 2 we 3 1 Positive Control o9-1aninoacri6d9i6ne 75 ug1per plate ------ 00032 965%2596 1 11 v6e0 a1m73 BackgroIunnNodrmLaalw;n C2o=dSelightly 4=Extremely reduced; rSe=dAubcseedn;t; 3s6M=oOdbesrcautreeldybyrepdruecceidpitate Neslon-Interfering precipitate; Ip=Interfering precipitate -- BioRelianc_ e -------- Study No. AAS2XK502001.BTL 3 Company Sanitized.Doesnot conTtSaCAiCBnI H-25170; Bacterial ReverseMutation Test with a Assa DuPont-8867 Bacterial Mutation Test Taste 23 TSetsutdysNuubrsbtearnce 1d:+ HM-S2J5I1K7.0S02001.BFL Experiment No : 52 sLtirvaeirnMicrosomes :+ Raaitsl3iver 59 CDaatlelsPSleateedded :: 41.J3anx 120002 VPelahtiincgle Aliquot : 2t5etrahydrofuran Concen:trapltaitoen HPluabteer Revertlaanttes BacCkogdroeund RAevveerratgaents DSetvainadtairodn Vehicle o0n2 s5 11 03 10 1 5 1 1 002 23 11 0 10 1 5 ` 0 002 8` 11 - 03 11 ` ` 150 0012 10s 11 03 u1 5 3 s00 o02 32 wwee 0 5 we 5 ` 1500 oozu 87 wree 03 5 re 5000 0021 55 w1ep 0 3 we 1 5 3 Positive Control 2-oraminoant2hr1a6cene 1.01ug per plate o032 171138 11 169 52 Backgr1o-uNnodrmLaalw;n C2o-dSelightly reduced; SsModerately reduced N4Po-BNxotnr-eImnotleyrfreerduicnegd;pre5ceiApbiateantt;e; 6=IaPbsaIcnutreerfdebryingprepcriepciitpaitteate BioReliance -- Study No. AASZXK.502001BTL 40 `CompanySanitized. Doasnot containTSCA CBI 'H-25170: Bacterial Reverse Mutation Test with anIndependentRepeatAssay `DuPont8867 Bacterial Mutation Test Table 20 TSetsutdySNuubmsbtearnce 1d: M#A2S5Z1X7K0.S02001.BTL Experiment No : 52 LseirvaeirnMicrosomes : WNoeneuvia DCaetlelsPSleaedteedd:: 24.5daXn 210002 vePhlaitcilneg Aliquot:+ 2t5eturla.nyaroturan Cuogncpeerntrpaltaitoen NPulmabteer Rpeevrerptlaanttes BackCgordeound RAevveerrtaagnets SDetvainadtairodn Venicle 002 10s 11 03 12 i 10 2 5 o02 11 11 0 Bn 1 1 1 50 o2 15 11 - 03 11 n ` 150 0o 21 11 03 s1 10 8 s00 oo 1102 11 n1 Bn 1500 o02n 12s mmep a 1 me 0 ` s000 o02n 125 wmee 0 . me 1 2 Positive Control me0thyl metha10n8esulfonat7e 1000 ug per plate 02 112221 i3 wr 5 BackgroTuanNdornLaalv;a C2o-d5e1ightly reduced; JoModerately reduced NedsrtBixotnr-eImnetleyrfreerdiucnegd)preSceiApbisteantte;; GePO-bIanctuerrefderbiyngprepcriepciitpaitteate _ BiSotRuedlyiNaon.ceAAS2XK.502001BTL a -- CompanySanitized. DoesnotcontainTSCACBI H-25170: Bacterial Reverse Mutation Test with a Assay DuPont-8867 Bacterial Mutation Test Table 25 TSetsutdySNuubssbtearnce 1d: ABA-S2I5X1K70.S02001.BTL Experiment Xo : B2 StLriavienr Microsomes : WReaat wliaver 59 DCealtlesPSleaetdeedd :: 42.J5aXn 210002 VPelhaitcilneg Aliquot :+ 2t5etrualnyarofuran Cuognpceenrtprlataitoen NPulmabteer Rpeerverptlaanttes BackCgordoeund ReAvveerrtaagnets DSetvainadtairodn Venicle o02n s5 11 03 12 1 10 2 15 o0n2 105 11 03 71 7 3 s0 002 15 11 ~ 03 15 1 1 2 150 0021 1100 11 0 10 1 10 o 500 002 1 11 03 un 1 u 3 1500 0002 11n2 mw1 ee fn 3 5000 0012 1u6n mwee 03 5 we 12 . Positive Control 2-0aminoanthr97a2cene 10 u1g per plate 0032 1464 11 993 161 Backgro1u-nNodrmLaalw;n C2o=dSelightly reduced; 3sModerately reduced N4p==Etxotnr-eImnetleyrfreerduicnegd;preSceiApbistenatt;e; 6I=POsbIsncutreerdfebriynpgrperceicpiiptiattaete BioReliance ~ StudyNo. AAS2XK502001.BTL 2 `Company Sanitized. Does not contain TSCA CBI 'H-25170; BacterialReverseMutation Test with an IndependentRepeatAssay DuPont-8867 Bac`tSeurmimaarly MouftaRteisounltTsest Table 26 TSetsutdySNuubmsbtearnce 1d : AK-A2S5I1X7K0.502001.TL Experiment No : BL Liver MicrosomAevse:ragNeonReevertants Per Plate + Standard Deviation Dose (ug/plate) TASS TAI Ve15hicle LToss 10 1195:92:65 15050 010:s 2011091s1%0 1550000 1102:s 032 1M23616:2 P5o0s0i0tive 1m75s+ 232 15063:62:133 Liver Microsomes: Rat liver 59 TAISIS 1134+: &2 112:: 21 19:: 11 21030++ 441 TAISYT 66:: 22 45:: 23 56:: 21 6952:21262 Wea uve 1103%: 03 11B2:: 10 1122:: 02 1985:: 183 _Dose (uo/plate) TASS TAIOD TAISIS TAISIT we2 wven - 1V5enicle T1e5:+ 72 11613:: 298 1100+% 22 682: 33 112:: 31 15500 1168ss 31 11581914::20 182:: &3 75:: 31 1100:: 01 1550000 115s+ 8111766612:+5 196:+ 33 66:2 21 193:: a2 P5o0s0i0tive 41466++ 332 167577+212186 1110++ 235 s6e:s 28 S1155:ean2 VPeohsiictlivee==VePnoiscilteiveConCotnrtorlol Plating aliquot: 25 ub BioReliance _ StudyNo. AAS2XK.5020B0TL1 4 Company Sanitized. Does not contain TSCA CBI 'aHn-I2n5170: BacterialRevAesrssaeyMutationTestwith DuPont:8867 Bac`tSeurmiaarly MouftaRteisounltTsest Table 27 STtuedyst SWuubmsbtearnce 1d :+ AHA-S225X1K7.0502001.57L nent No : B2 Liver MicrosomAevse:ragNeonReevertants Per Plate + Standard Deviation Dose (ug/platel TASS TALOD TAISIS Vehicle 19: 1942s 18: 0 TAISYT We2 uve 6: 2 10: 2 1505 150 1162++ 65 1102:: 73 1260:: 64 10+ 1 182: 15: 4 76:: 1& 1124:: 14 62 3 2: 8 5150000 5000 152:+ 05311908: :3222 2136+: 43 9+ 3 16: 8 16: 2 56S+: 23 1130:: 44 3: 1 10: 2 PLoissviietrtiivMveiecrosomes:2233R8a:%t 1li20v0e7rT75m91:: 66 4377:: 4a1 776600+21733u1r17s: 88 -~ Dose (ug/plate) TASS TAI00 mA1sIS_ V1e5hicle 12690e: 25 11898:: 1221 115:: 33 TAISI? we2 wva 995:s 14 170:: 32 s1500 500 27+s 3311598:91:77 1162:: 52 20: 6 19: 25 10: 6 a5s: &3 110:: 20 5+ 4 11: 3 15500000 2129:: 74 119855:: 178 1160:: Posittiivvee ___ l1o0l1i1+ 3366 999938+: 689 116666:: 42 86:: 31 1142:: 34 88 11669++5522 99939:+13611 VPeohsiictlieve==VePhoiscilteiveConCtornotlrol Plating aliquot: 25 ul. B-i--o_R--eliance StudyNo. AAS2XK.5020B0T1L 7 `CompanySanitized. Doesnot conTtSaCAiCBnI H-25170: Bacterial Reverse Mutation Test with a t Assay DuPont-8867 APPENDIX A Historical Control Data BioReliance Study No. AAS2XK.5020B0T1L as Company Sanitized. Does not contain TSCA CBI H-25170:BacterialReverseMutation Test with an Independent Repeat Assay 'DuPont-8867 HistoricalNegative andPositiveControl Values 1998 --2000 revertants per plate soi eT me | TA%S 7. IL 206 322 56 TA100 LAB 568 28] 18 1371 736 |..74) 258 198| 2871 TAIS3S 2 2 2 378 978 1640 -- ats ssallianl|of| wElel 7w|i] si]ismoe ho salsa] SD=standa (including rd deviation; Min=minimum v but not limited to deionized alue; Max=maximum value; water, dimethyl sulfoxide, Neg=negati ethanol and ve control acetone); Pos=positive control BioReliance -~ Study No. AA52XK.502001. BTL 46 H-25170: Bacterial Reverse Mutation Test with an Independent Repeat Assay DuPout-8867 APPENDIX B Study Protocol _ BSitouRdyelNao.ncAeAS2XK502001 BTL a `Company Sanilized. Does not contain TSCA CBI -. Smtae 2H0-25I1n7de0p:enBdaecntteriRaepleaRteveArsssaeyMutation Test with _ OR Received by RAJOA 5 DuPont8867 APPROVED Roe yVr ARSCSOT 0 rerrose 1i :Bt BeT re Mitton To Tr Saortegrsiilrtybmrnsmemoetoeie toericoEihof cms eby 20 srovson 3 2 Sl1oHiPo a cNermeetlCsosopr TpooteRhvtatehnese [R-- Htatie,e - Umar; Drown Email: maria doancr@ussdupontcom 2EEtsar (wmasm 30 2I7 DSaBvioTOFTEIST 44C0C(oAnamRmoTL)suOBSTANNCES 32 Tesesler:e I (H21 m() oteenmdiey IT fj-- omarep, inte [ @ BIOREUANCE BioRelimee Study No.AAS2XK502001 BTL 48 H-25170:BacterialReverseMutationTest with an Independent Repeat Assay DuPont-8867 SpossorProjctNumber: _ Duo167 34 TestSubtace ChansBoionReliance Study Number:_ AAS2XK502001 BTL [m TE[e in| ca 0pomopoesnioteionnfotofrytdeheeestraoeitfnsnBihomeenSsG1d,igod2o0hcuambtonseeSnatboTlhheoefSS1tpdepsiagiwihll oprfaeyiaikold Ni fhvs n(ore vi, 55 TotSt Remi e Spl TSheptoiornof sresplof esssoill heresponsi of 40 TESTINGFACILITYANDKEYPERSONNEL 4 Nee TBoirhicanTesingFay 42 Adi Ro0c0keMMoDC,sa206iD0ilve --- 43 StyDincir. VF Phoe:c0t1O6,1Ra031g53e1,MrS. Eri vagrr@hireaccosm 50 PROPOSEDSTUDYDATES 51 painSoeDun: 0002001 52 Eapeicon Temiosico Dae: 25a2002 53 DutRegonbus: reson SA FtReptus: 2 ek aterSporepeedsat 60 TeSTSYSTEM WTTAhELeScEtSrrknsdidTnesAbwIie?lmctydseGrtbreesd.dbeyoAprimennlsitoan.i(1s9i75nsncdooepsoTlASeSe,rTAsIiOOt,s I wis [wo| PracSPOTSI0) 102001 TeTams] Page2011 BIOREUIANCE Bi--oR-el--ia--nco StudyNo. AA52XK502001. BTL 49 Company Sanitzed. Does not contain TSCA C81 - p'oH-t25170;BacterialRevers:eMutation Testwith DuPont $867 [pa TREE [i rin s] BioSRpoenlsaocrePSrtoajeytNNuammbebr::__A_ADSu2bXoo5t08080671BTL [ec [rae These[Wiss| ope Tm| |irs |es|ir [Lawns T5) EcaC pcrh.,apdhiiI imonl tesT iteorsnithnetccohTnatonincm,esiaenansdidb]ilynttoomo[omteuaioonfgnneTnhesi--si]n matrxchiiiinionncetlbeeessasoceyfhsch.aecneilTclTwaeeltledridclsehconaistihTiAhehSceSto4semdmirn.eTgAsTOOogeeap tdleocbr hyaoiSneothogcot cpolmaspiiltdevi(lycva1arvmieindwgsibehesRhbeeyiceond.einItgheapa0speceasnssoabtaecdi)hoDNhAe.bpipcss hobss ThmoAnSdcSiy1edsaTedALGsbSsrSb?easaisieptr.ei)vobernyedfretoamcghetissi,1dineTvdAeeVpeeSnSden1TcerAe(Isvc.ecoopoltyvy)beyfobisysosniosn - {5Tooh2slebiscneolilcnclheatndegetrefli.ntiten1D9bNo9rs0Ag)Ti1enexaclAeilTsryibosamnsaeisapnesdWisFh2esiioheernrc.bTryyhipsotbpmiheeetncaenonvngseieScsetwicmtahoeinrnwntsetr2p. l7e6o,mioornomcechiain ihesoriige m1abuiai0 bboaoppnreeTmoisoe(OporsiesVoofa TKNhUiaenignolnSolmio)p.CohvifmCeeaolirfuoonntslfiaeI,itnDioettsriaeiylnkss.dwTehrMeear.iencseaiBlvuetdcedsr,istlAunbwrtoem,DrS,c emstiBrsi ocfe Aomcmes., 70. EXPERDESIIGNMANEDMENTHTODOALOLGY cWhopePslitsA1wdpipsnohcisaeiwdvieilccoobocnncntsst$ww5ilisahcbitpmveieoeidns,miApnDostdSToevAeeSk.Hd,ovsTelAoeTvfe,slTkoongSrwiethTsposoroypm s POISPOTL 1nd Bi--oRe--lian--c -- Study No. AAS2XK502001.BTL Page3afil 50 [)BIORELIANCE Company Sanitized. Doesnot containTSCA CBI 'H-25170:BacterialReverseMutationTestwith an IndependentRepeatAssay DuPont-8867 SponocPctNur: _DaPonas) BloStkyNeumbser: _ASI S0201 871 74 SomlyDeserission UdnocrlcwermsisalthieoSnpwpoeinnlssloirochnonapdunoci4cadsitthnre ofcbt0embg/cLm.safnovspeiols,cvc+ iseoblbrilily o507e302m1og1fa5p .,fdor err ipclviee dien(VCaf eArSientGx7s.Bu6e m8p.d5 tor vodlien(iiCee AsSdttw64sa1y7d .a5)CaAS aSioicknocfo(pCmeAmSlo6en7,6,0-wU1hp)i1Tc0hh3pe0vietfisnlp.ofafocnhuoikneosvfivBlelehbieNesmkdlm,0b0mime.dtfo ricvin 72 ln TosiAssytoSltDoeLevels `SaelepctiTeohnifpspdorsipveoelleosxfetheye tittlgsbeuccosmasyeewinblydlbipenagnprdemTiAoSh,e TonAiItyy, ScTohAmIceS3nSu,oifoTnA5sT9Ssf2Ycti1e0nd.WsUEntl2ae,assnohien.dtiocitsedepagehuedreowscieoe nbeyst2aebSdphe1ersr,t aackHesiigaghhdts --~ dlolenoewidinlgmbegghaiignshTyswielcribaneglpsdcooessyreivosDnofsoehew0vilibeeoocfcgehodyabontahotdook ioopenlrhececoeptrtimcrgyseayw.iFihocbraensddaycscroiinl.,giVvehasseoedpuihlosen,tboafeeHniye {Hiogbheipsgtehdtstdooeeveeevieelvweicsl.SbTtmelgScp.eedForipl ebctghteimyi,daesrpcegpodto bololiyon lee(vvee1liitlseeemitmhn5esgdpoltuelaenov) 2ss)dshescsebvieodnoostepore.acaenksssedaBissdGoo 73 FrequencysdRoweofAdniisrion T2m2ht0ehAotdrtosygys(9i5gw,ialTll biyedcteesasyeptbeybArrtebsefts.hoo(s17vt5o)id0ecdpteieswesdiceboy pvgeietsoof ln ofchemical tensMC, 1975MeaodAmes 1978 Al2mlByeoishleolubnneigetpoerfiTssheeoeyefitrvesleoyeSblnvyebDeisnoedvdernyitwhlemttnbeesdoy les hon becand 20ovo pone, ratereo ov Prac SPOTS L201 Page11 @ BIORELIANCE B-i--oReliance Study No. AAS2XK 502001BTL s1 CompanySanitized. Doss notcontainTSCA CBI - 'H-25170:BacterialReverseMutationTest with anIndependentRepeatAssay DuPont-8867 [om Ja [|rm [E52 D`iSpoonsoRrPSraoljleyctNaNeucmbbreer::A__SDDuPConSt0$30617 TL c(cm8..1vaciCvpuorimoipnsosueys.ss, boiesvSoepsommoenartsnmivwidel)bo.efvTshlsiaduciimdneidanebesoi5lncbgaepdxiownneys OPGErCuDadGmeuisdeclnine(Sp7e11c(i.bwe pAepaacsy19o9f7eRndepgliisohedGFebarsareoy1t9y98)Tess CfHo 4 Coots 741 PositiveCoeds Aplicroonpieommopnestoff paosri incgots sodestersinpied concretly - eS TAI, [to | 1e 0 | [Lm|moeoe] Lom| [mts|| [eanoene [on] 742 NegaiveConels `A{pmieloospei5r9teanceigvaattiiBvoenic.soTnohtenolnbgwiuelivbfeeorpvoleeuodlffxhicelscbceetitehewsviiineeishos0nde., Tatra,bhested mo vikcomeswil nd. 743 Sey onto Theeocthcotns nedyest sto divonsd heShamand 9 mics 75 EaogemosMeshal Acivsion ATvchiteh$oa9Bg7oeo5ge 4erd wiem llvber5ep pwirlolfAreroi s.cdh l1eh5S5r epcm0t0iDmcui gci.tFioaoidnsc uosspeysde. ose.Th 35wil be chpees1dsorerns pny Proce SPOTS001 1an2001 PageSof11 @ BIORELIANCE -- BioReliancs --e Study No. AA52XK502001 BTL 52 `Company Sanized. Doesnot containTSCA CBI H-25170; Bacterial Reverse Mutation Test with 2n IndependentRepeat Assay DuPont-8867 B`SiponosorRPrtoajoeycatNNuucnmbbeeerr::___A_ADSuIPoXnItC4S860720B0T1L e0bgeerlin0Jd.a5mpioEoxhecshbbaroacrcvToefAm9Iw.bdm11p2dmciwyillblessmnybidncoeceisallfyorms Iconimnet10%pie 59we,ghen9tiel,lxtShawbadShieds owilsh chofiacorposoo0 2m-1tii0c0oltailMnapm1i0dho0amdpeMnipnbehidirnputckpoioaild7.e4p.hToskpm7iAee,.h8miMs MrgCld,end 3539mmMinKSChleinn 76 PrpeniaofTeterSin OPiveepnrtoeprciunagrersofacinhlsabeikcnTvilolcboefseoomrhethcde mpsdope1.armeva,erAtdphls okfoefo0og Torporimoncgamaoepyl,yrec1.2h5Tolsahtk7de4rfn2c0kusbwtpiorlihnipllaabcelepdr12oogersetsiegsk0ebiebgeitnahiiaioinnd oth - Aclumltclyloorseofristlhibtbebyyarrvtioesosinodombefymisacgpeosnc.CsouveposvwbmelirnbsecsmoafcetofiscishScaoamn baton ditoprima 1 clin. 27 To Sysem etsion BPSauhcmh,pidooGuweiemlveh,bePcrkcsawii.tnh cokeyieont7 3idies bhe Bbito,lit 75 Ton bcePepsin Usresostes,iAdlt foe vitseo, cstdsoigstisldlietrsowil bepiropne umrceaon 79 TrsmetofTeton SO2Dn0eLbaoloffvimilokbl,s(e0ct3mmeLi)wnofpc5se9gdiisa4oS5hr4ap3n.oWish,eoc1so0o0k.cofwyieletrbsahiddnwe1d5 ooyieest cmsineodisndsovcemncoricctciecoivooilidccWenioflfeb2cop,psesoi.oflmtThioinfilonieibeaovnnnwi5s0letg,1:. PascalSPOTSUOL 1dm01 Paget) @ BIOREUIANCE Bi--oR_el--ian--ce_---- Study No. AAS2XK 502001. BTL 53 Company Sanitized. DoesnotcontaTSiCnA CBI - 'H-25170:BacterialReverse Mutation Testwith an Independent Repeat Assay DuPont-8867 [ Sponsor rPictN Nebr: _y_ Deut--1367-- Alpforvoitxneigmhvaele4cyu1bba7atis2osnopluoisdd,id7l e4be2h.atPesdlisl2tl8tbs.isvoertcinddniocbitfyx 0 Scoing Teohtencb opngtain ocfoa tmebaplcariscbn dapcetkgc,roEuvnidscn onnensgwoiwflirlhbeye avwibltdbesocrd evtddomfcaea of PrieripilaTiocroinclwoiwlilbeliocncilnsugeoddfidmpheperccoceosbaosfinehpe eadbcbetyaofibrnkapercneidtlfaodoomin imepeion 11 TorSin Venton Ochnectkheeddafyhoefpoeeopi he raoncgeaelhearsyci,dl$i6c0, sicubiswillbe 0 CRITERIAFORDETERMIOFNAAVATLIIDTOESNT - "The llowinreamutbemefor he tei acybo bcos vd: Bl ToneSei gy T1oo5ltdermeonusstictohte,presOcipaevhofiythre yfesmtleovonrli,ncTlohSd.eeoesspticteheepsesarscyeiof {ih0eearpvSariikcnscouifgbhhetesTmoMdtIeOcnplsleesdeiRrtcys,osofiraslr.mghitoeTo,dofeTmaAoSn2H.saenod TATOOmtcisoeto pile 2 SpoRenvermtBacekgoonFnreesney h((Baocecikctcsi)ie.oynT:ahTbepAmiaDes,nnea1o0e-fvc5s0or;ouaTrrAptdIeu,s,pe3t0l-vel24eit0;ssteTbpAeeIilSiwSnei,. i3c-4uo5ore; sTcAi pTrSgtS,cc3oa-sgb3te0.ss Weom, 10-66, 83 TerminTies Torcsmetbet paptpaoeramrbearnof0b.c3k0selappsmtlalelei tancee Proce SPOTS001 1an2001 PageTaf11 [)BIORELIANCE BioRelance Study No. AAS2XK502001. BTL - B- 54 Company Sanitized. Does notconTtSaCAiGBnI `H-25170:Bacterial Reverse Mutation Test with =. Assa) DuPont-8867 SponsorProjectNumber: _ Duns4367 BioRSeudiyNaumnbecr. AASIXKSOROLBTL . 84 PosveConrVals Eeipcehciavnpuosnipegcaonecovmaetvueeo(cviite)ffortach3.k0.s68 creeov 85 Toy oAfdmvoetinanotsoipecreloeremeroedtleinveeod1otsa sevas wig2ll5ab0ve%reicieocodoltnovcaeales(elessresydcdeion d2iotedbovecslocriaecmhiepebivcdbk,y aenalooptvd.oIpsonrtGdiroen.povefeittamotpylnilohn,vteenpetipcwoouinsh)oo pochann ge do e eels. 90 EVALUOFATETSTRIESOULNTS CFmooerehncsetvrbasofpeectlibbeecoevalestpoisoiotivse,beirltSuni:tncvoee4 idnonealtodffcoesceafsieng 51 Sm TAI mdTAISH ~ T hieedosetreipoense cntfoo reirtT hI n3m -- mus-- pai c--il 52 SionTASH,TAIOORdWPL Dieetedcetistwpilo.lbreeisgdapt 0veirfeserfcnrs20-6 een overtgtavhee cektolf 100 REPORT ciuAipccrltyhofdteherievetsloeftdissswyedwillGbeepeneirend1by nhle yTsinogfLabdour Teordpwritll + TSonsotvySubhsotianscceme:ebienpsoopwwr,asi.sCAelSemvo, i0nhovecopbhyssofbaeneslsy,dipinso,ti, +`Sboolvoe sVeiiscel:veftahielifflioorcohw,si.cofveilsslysad sabiyof ust + Stan:sin od amberfc.pe cubisssnchris. Prac SPOTSI0) LimH01 Paeoril @ BIORELIANCE `BioReliagee ~~ Study No. AAS2XK.502001.BTL 55 `CompanySanitzed. Doesnot contain TSCA CBI -~ F-25170: Bacterial Reverse MutationTest with anIndependentRepeatAssay DuPont-8867 SponsorProjectNumber: __ DuPont8867 BioRelaneSodyNumber:_ ASAS 200B1TL + mTeimtvreconotfirpoanssc:m,poucnhc tinofgteceo psocn Cpeirwperlde;c wyimptheaandspo coeocpfheonredir ooneolfmcd cabsonlde + mo Rebneis.osi figevsoivfeen, pyocs:ei,icpssuopsfepiperaetscaiwiov.sinfaiadd;cvopoilooacr:cedoudrsertgieompwesmd pCuotiievdceouirthdgan,esmesatnsdasasnadidddevvis.Hsecl pie iin J ---- + Conaion 110 RECAONDARRCDHIVSES SBAlrLorkeeds,ea4,c92p0roc and Reopckrvisllei i,lMb D2065t0h,ci PethciizSn OP,y pafogSd sraedda=sr S2dioelcolibsmeieornon5dd0efsthrtoGrdltwciholrperoosynbrosefchopheeieid rc3a0sin,ehAelchleoopSdypyonielbeils.rbeeireceadnidfo BloiRvefar A lsonae ofnIo eeu. --- 120 REGULATORYREQUIREMELANBOTRASTOIRYGPROACOTIDCE OTdhTieosrlkiplongrsyf:coBthuaesTbieorRgnewofviCeeoMn1lo0o,conpmupAblslyswyi)l,bhyNOOiEEsCChDDA,Gduadidie,liFnbefr4u7ey1 1(9G9SemCnDdi,c vRietgihsbreaiIonaosfPonrCaonrtrafoerH0ca0nHtesaUtrso(i1o99ncsodftT19hs5essRenieconds 1 iPoTrhcicissctedRepigailubieoepnerrffoeorrdmNedoiawclmipnploLsnacybwowisitlrhlyooSeshpaaocdviisi(opGesLoPf)thS.eTaohiopddoLOaopboelrn,aitnoargny Pcnrpooecmcepiilroenes(iwSilhHbG)eLopPf,eBithaeRaSaOtliPtaseosofbmyBilohtkesheaunacleioaAdlsesssyedsPUpookcoholfe.BTiosyeblroprn1cs npdpcyopreiinichlelpsey,h.etA.SeeodyeiedpOoahfsSexcshenspptoacweicdldirniccogetheeddpreevi foeqdrspooroftr.eTuhcreh inspeictoino,nweyromedpoOrLcPcdoouphlnScteyeDtimcetkwsinllhbeSchaiddyeDdinthofmderpnsi. ThIins `cosxrtcaaptebimoienntswisl0lyicisstectoohfmeOpeLleP,oguiifdoeplriinela(sl)bw,iitnhcwnlhoidsicnhgftohiesctruodsoyinsscoofmpclpiarnctainidainoyn Proocal SPOTS Limm0l Page Sof11 BIORELIANCE BioReliane ce yessme ------eeeemmsesess || Study No. AAS2XK502001. BTL 56 Company Sanitized. Doesnot conTtSaCAiCBnI H-25170:BacterialReverse MutationTest with nlodepend~~entRepeatADus ponstss ss)y SponsorPictNaber:__ DuPont) BioReSllyiNnumcbeer: _AASIXKS001 BTL oUnfploelsslseoadvoriafnoglgaoeewmiiestnsrguaroionnidteooonhtoehtfeceeoksrypys, ssnddsdlossihnagsllu1tionms awilnlbeedi0p30 10 REFERENCE pAndmstm BAnXn.eMstcwCiiactn,hsnS ,J smo d Ym akE.o (19,5).n Methoa dsfru detcink gcaiMma. osgieoens GExrceherni,chMiILcLo,,MnadttMounsiRle,seWaJc,h3(819373)5,Mitagntestingusing 5" reves in RReeIggiurslriuomiroyanGeoCnfoPcnhneuiemhcayecoTeosnsasflHoarfmoPmreHihooriaaonnmU(sC,.H)Oou52fktTcdeocschouimnceanlStpmRececoiimeeimnenpnieetcdssiofoofrr aCdoptiUon T5pIho4.Eoft2e,159.ICH oc 6 Joy 19, 19%. Fen Reger --~ RI`eOnghnikoaicnsyToCefosPntiaenrrgosocsfecPsaotrnlmHascafeoesr inFcuis.mi2Un8sd(.oCcGHue)moetonftnciTieyec:hAniSetRtatefaoesBeomeprsy ffoor sp 4ofthe IC procsoa ly 16, 1997. Fer Rego6216012600%, Raven2,b1e997r. UM SSATac 510.l9150a 48mAmeso, , BstNns. e(1l9o7f63)a.0D0ectehcrtoiosneio:fGccaorioooong.nsPsoa .mNniengAnmcsoineSthee. SMictnaUSeA1T,sC2ho1,S35.1l53Y.anmakai,E.n1dlASra,yBmNo.if(1057c05)c.DrheestteooPrfccruNtraioin!ngoeeesa1nt0 TMaete,iDAtLudRaeAsseir,1B3No1.72(12n91635),,Rid hodfoteSone Mercy POAaEdsCd,DeFGdeuridr1eyltibne1e9O48E71C(DGGordnleiTnsofxr ots:TeBsaticnkg sofCRheevsse,MeptuilnT5e7,ONBiCsh, SWapilmnrosn,eellPa,pNiimdroi,omA TAWIeGlRdw,iDtJh.EsxcdherGicahacbolleWDPL,?Oe.si(19s%)t,iCo.mMpaorigseonnofs Pra SPOTSTOL Lin01 Page10011 @ BioReuance _ BSitRuedylNaon.cAeAS2XK502001 BTL 57 CompanySaritizad. Doss notcontainTSCA CBI 'H-25170: BacterialReverse MutaTtesitwointh am DuPont-8867 10 AreROVAL Bi`oSRpeonlsaocrePSroujdeyctNNuummbbeerr::___A_ASDuIPXoKnSt080617 BTL TTMSoora--R"aDmaane 03-9bac-zoot MMeocg:enRopenepc ane ae. TT ertdl Rel SlyMago a 5Toc 2001 O ob becR 200s ProdITSEOL Lol Page1011 [)BIORELIANCE BioRemnee -- StudyNo. AAS2XK.5020B0T1L 58 Company Saniized. Does not contain TSCA CBI H-25170;BacterialReverse MutationTestwith a t Repeat DuPont8867 APPENDICX InffoorJarpanemse Raegultatoiry Agoencnies _ StBiuodRyelNioa.ncAeAS2XK502001 BTL E) CompanySanitized. Doesnotcontain TSCA C81 2an5170:IBndaepcentdeentrRiepaeatl ReveArssseaMutation Test with DuPont-8867 ReportofResultsofReverse-MutatTieosnt in Bacteria 1. Tester Strains 1) Procurement. Obtainedfrom Dateobtained tDhaetsetainisnpelcotteidn storage TAI a a ; 11 August 1 tans brs Suiy - ne We2 uA NaotfioInndaulstCroilalleactnidon| by 00 (@kMIO1) Marine Bacteria Wrz kuin) | Aberdeen,Scotland Tgpoor 1993 mansrch confdiramoefdwyoen the @ Storag Composit DMso oval 21.) 5S9oMuricxe, Storage Temperature, et.of59 [vem | Prepared on 17 October 2001 (Batch R654) 26 November2001 (Batch R656) Name 1d mol of _ SBtiuodReylNioa.nceAASZXK.5020B0T1L Company Santzed. Doss not contin TSCA GBI He25170; Bacterial Reverse Mataion Tes with an Assay DuPont-8867 CC Tow T | mom] (2) Preparationof $9 Speci+eo s, Straisuin| Rattus normveegigcuss, Sprague Inducing substance EE FE Age(iinweeks) 98 (BBaattcchhRR665564)) Sminiuihangsai raton wt | 38,05 gig a 181 (0 19(Ba8ch R64)|(kgweighty eight 18710271 g(Batch R656) body weight a. Cee e [wn 3, PreparationofTestSubstance Solution Grade and/or Tetrahydrofuran (CAS No. 109-999) `Aldrich Chemical `Company 10035281 Gold Label, 99.9% `tShteabsiollivtyenotftest substance in Method of suspension when test substanceisdifficult to dissolve Notapplicable _ BoRemee Study No. AAS2XK.5020BT0L1 61 GompanySanitzed. Dos not conTtSaCAiCBnI aH0-2I5n1d7e0p:enBdaecntetrRiealpeRaetveArssseayMutation Test with DuPoni-8867 4. Conditions of Pre-culture [ oembon [N |we ater[Le oto | Oxoid Nutient . CH.B232622 I 1241 bows `iStnoraogectiumetolabneadgittnenmiipn.ogfonrfom | 2t0 5hoursatambieattemperature shaking culture EF Are Storage time and temp. from " Model and manufacturoefr | Ney, Brunswick Scientific, model G-24 M(Gehtahiondgotfypseh,aksipnegd, ie) _|FO 21255 rmeviin.) _ bCiultudre vessel (shape, shape: cyli:nder, 200 mL. [voume [reo vonytinosti7m] 5. Agar Plate Medium 1) Top agr Ase [Mme| mise I (2) Minimum Glucose Agar Made in-house: Ase [Name [ems [Ma | i econr Dickine on | lo00rDKSQ _ BSitouRdeylNioa.ncAeASZXK502001 BTL @ CompanySaniized. Does not conTtSaCAiGBnI Han-2I5n1d7e0p:enBdaecntetrRiealpeRaetveArssseayMutation Test with 6. Test Results - Judgement of the results DuPont 8867 Reason forjudgement and referential matters: NaobspeonscietoifveArreoscploonrs-einwdauscoebdsreartvleidvewriSt9h.anyofthetesterstrainsin thepresenceand Referential matters "`Tchoerrveechtilyclaenadnwdeproesictaipvaebcloeontfrdoeltevcaltuiensginadmiuctaatgeetnh.atalltester trainswerefunctioning. _ BioReliance --- Study No. AAS2XK 502001. BTL 6 Company Sanitized. Doss not contain TSCA CBI