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ARA26 - 3292 45 TRADE SECRET Study Tide F-25509: Repeated Dose Dermal Toxicity 28-Day Study in Male Rats AR 226_ 3293 DuPont 11763 TEST GUIDELINES: US. EPA Health Effects Test Guidelines OPPTS 870.3200 (1998) `OECD Guidelines for Testingof Chemicals Section 4: Health Effects, Number 410 (1981) AuTHOR: Carol Finlay, B.A. ~ STUDY COMPLETED ON: August 4, 2003 PERFORMING LABORATORY: E.L. du Pont de Nemours and Company Haskell Laboratory for Elkton Road, P.O. Box H5e0alth and Environmental Sciences Newark, Delaware 19714-0050 LABORATORY PROJECTID: DuPont-11763 eons? 7sChC8 ~ compe gone0d. 90%" -- meres 2H.52.5D5a0y9:SuRdeypeiantMead-lDeoRsaetsDermal Toxicity DuPont-11763 GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT "LTahbiosrsattuodryywParasctciocneduStcatneddarindsc,omwphliicahnacreewciotnhsiUs.tSe.ntEwPiAthTtSheCOAE(C40DCPFriRncpiaprltes7o92f)GGoooodd Laboratory Practice documented below. (as revised in 1997) The item listed did published not impact in ENV/MC/CHEM(98) the validityofthe study. except for the item u`TnhdeerspGoonsoodrLcahbaorraactteorriyzePdratchteicteesSttsaunbdsatradnsc,e.botAhltthhoeuvgahlitdhietycahanrdacatcecruirzaactyioonftwhaes annoatlypseirsfworamsed considered acceptable and therefore sufficient for the purpose of this study. `Applicant / Sponsor: EL du Pont de Nemours and Company `Wilmington, Delaware 19898 USA. ~ Study Director: / Carol Firkay, B.A. Staff Toxicologist Hd,las 1002 Applicant / Sponsor: DuPont Representative . Date in TSCAC8 ~ Company Seoa. DoesM0 e-------- epErx-- emaee-- seepb -- ee -- ---- -- -- 2552D5e50y9:SRyepeinstie-eDoRsaesDermal Toxicity -- `QUALITY ASSURANCE STATEMENT Dwon11763 Haskell Sample Number(s): 25509 Dates of Inspections: Protocol: November 22, 2002 Conduct: December 10,12,16,23, 2002; March 5, 2003 Records, Reports: March 3-7,12-13,28, 2003; July 14-16, 2003 Dates Findings Reported to: ~ Study Director: March 5,10,13,28, 2003; July 16, 2003 Management: March 5,13,20, 2003; July 16,22, 2003 Reported by: K `Wonda K. Kplly Quality Assurance Auditor Y-us-2003 Date --~ Company Sanized Doss pCO TSCA CBU -------------------------- [SaryrSupt as---- Dwon11763 CERTIFICATION `We, the undersigned, declare that this report provides an accurate evaluation ofthe data obtained from this study. amEvasluratiaon bey: J, Ned BGE e HDVS G _1=Av=622000033 Pai eeDriplComhatmeAFCu.bVoPl.gtdM A Th,FeCa-r MWoem mDeVT Very Fug Diplomate A.C.V.P. -- I~ Ave-ase3 ~~ Approvedby: om.Na iLomkaen, 1 AVG5Zoe oebySty Dict:LF Srna -- Atug 03 . Staff Toxicologist _ ee --e ---- lee-- s ---------- Company Sanitized. Does not contain TSCA CBI H2:82-5D5a0y9S:tRuedpyeainteMda:lDeoRsaetDsermal Toxicity Dupont 11763 TAOFBCOL NTEE NTS Page GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT wcrc2 QUALITY ASSURANCE STATEMENT... 3 CERTIFICATION css LIST OF TABLES ccm sss | LIST OF FIGURES wcrc LIST OFAPPENDICES consis STUDY INFORMATION consis) STUDY PERSONNEL vss sss 10 SUMMARYrns 51 INTRODUCTION css 12 STUDY DESIGN css 12 ~ MATERIALS AND METHODS wv 12 J B. TOSSUBSIANCE...crvrnenssnenssnomsomsnemssenmnosee eee 13 D. AJ NMal BUSDANALY v -- o erems nn--n t wmmsm----13 23.. EFnvieraonndmeeWnAtCda.l..Conon. ...rrooorrrroermem seEm AT ------3 45. HIedaelnttihfiMcoantiitoonring Progrrame.emm------c--rmnm-- rrermn--mmm---- a14 EF.B. PASHSOIgSAmPeUnIto1l0 eGrrrorurpsrarnsdmeSnWmAnYesSrtmmIs.er.e.eeenrereereeremrereereeseonesrmee 1 14 G. H. Test Substance Preparationand AAMIDISUAION BOGY WEIGHS... ..............u..ownr corre 13 19 1 J. FMooortdaliCty oandnCsliniuacanlmdOFBpoSCoItdVEAfitFOGNoISenn.cy..............v.v.e.vo.rre.r.meenmrrmsmommemsmsmmsnsoesssnesnoorrnso 16 16 K. L. TCloitnailcaFlluPoartihnoela0ngdy EPeVrAflIuAorOoN0c.t.an.o.i.cvA.cirdvLvervvelrErVnarlUaAntsinoncsm.s..s.o.s..e.nc.s.o.r.e.r........ 16 16 21.. HClineicaml CaROaMtnSdoCOlMUoIIOgNy 1.. tm ssesse----------r17 3 Urinalysis. M. ANBOMC PathOIOEY EVAIUGHONS am--n ve---------- rrr 18 N. SUBSEA ANBIYSCS...rsrsnnmsnessmnme 20 Company Sanitized. Does not cantain TSCA CBI ------eee---- TT -------------- H2:62-5D5a0y9S:tRuedpyeaMitneMdaelDeosReeatsDermal Toxicity DDuuPomnt a1176s3 ~~ RESULTS AND DISCUSSION worms 21 T-LAi.feMTeOaXnICBOoId0yY Wc eightsanr d Body e Weight Gv ains...asse2211 BC.. FCloiondicaCl Oboservn atioS nasn,dDu FeOr0mdamlEfETpIVGAt ENlci yu.aa.no .dt.S.in ..oU.n..V s.m,u.vm. srn. oenmrs 21 21 DEx. IB0I-OLiOfdlFICOUNOCIHUNSAIROBNISYc SIS.oo rv n s e er nns ssn 2222. ClinAircalHEPaMtBhOoIlOoRgyY EVAIIt AtIONS c s re oss2222 Bu C.. CCHOBIGCUAI!BOCNEMv ISITY w c o o vr ee n 2222 D. E. UUriBneRaIndYPSIsImSa.FIcUOsFsACssso.s.sosvvscsescsorensesnsmstmmsenseooseseeonse2e 323 F.. Clinical Pathology CONCIUSIONS ....vrenrasosmsemseenennsoson23 ATAAtomMicOPTatIholo ogy EVAt INAHOs NS.c.cvossusmssmsmsssssssssssssmmsssmansoss 224 Bu OIA WEBI... C.. GOSS OBSEIVAONS coven enon oss28 28 DE.D. AMDICaTOOSiCOcPIPCAtFhIONIIONEGYSCONr CIISIONS s vr s s 24 24 ~ CONCLUSIONS ccna 3 RECORDS AND SAMPLE STORAGE worsen 35. ST APPENDICES wos 15. --_ oa. Doss sete TSCA!ost companySon me---- 2H-82-5D5a0y9:StRuedpyeiantMead-lDeoRsaetDsermalToxicity Dupont 11763 LI OFTSABLTES Page 1. MEANBODY WEIOGFMHALETS RATS.. wdmmmm-- 2. MEANBODYWEIGHT GAINS OFMALERATS... 32 3. MEAN DAILYFOODCONSUMBYPMATLEION RATS... w-- 4. MEAN DAILY FOOD EFFIOCFIMAELENRACTSY... 5. SUMMARY OF CLINICAL OBSERVIANTMAILOE NS RATS... 35 6. SUMMARY OF CLINICAL OBSERVATIONSINMALERATS POST DOSING... winST 7. PERCENT SURVIVAL OFMALERATS vss 38 8. SUMMARY OF HEMAVALTUESOFOLRMAOLE GY RATS.. wml 9. SUMMARY OFCOAGUVALLUEASFOTRMIALOERANTS... 10. SUMMARYOFCLINICAL CHEMISTRY VALUES FORMALE RATS.. 42 11. SUMMARYOFURINALYSIS VALUESFORMALERATS... -- 12. MEAN FINALBODY AND ORGAN WEIGHTSFROMMALE RATS... I 13. INCIDENCES OFGROSS OBSERVIANTMAILEONS RATS.. 48 -- 14. INCIDENCES ANDLESION GRADESOFMICROSCOPIC OBSERVATIONS INMALERATS, ss ~ --_--_--m Company Sanitized: D008containTSCACBY 28F--2D5a5y09S:tRudyeinpMealaeRtateDs eda-lDTooxisciety Pa LISTOF FIGURES 1. MEANBODYWEIOGF MHALETS RATS.d.. so DuPont-11763 Page -- LIST OF APPENDICES Page A INDIVBODIYDWEIUGHATSL sss 76 B. INDIFVOODICODNSUUAMPLTION... A ---- C. INDIVIDUAL CLINICAL OBSERVATIONSAND MORTALITYRECORDS... 83 D. INDIVIDUALCLINICALOBSERV~APTOISOT-NDSOSING....c.csnn 95 E. INDEDIEMAVANI DERD YTHU EMAA SCORL ES... 105 F. INDBILOVOD FILUODRINUE AL LEVLS.d.. wm PA: G. INDIVIDUALANIMAL CLINICAL PATHOLDOAGTYA vc... PR --~ H. INDIVIDUAL ANIMAL FINALBODY AND ORGAN WEIGHTS... smal 1. INDAINIMVALPIATHDOLOUGYDAATL A ccs154 -- -_-- `Company Sanitized. Does nol conto` TSA CBI oe 2255-5D0a9y:SRuedpyeainteMdalDeosReasDermal Toxicity Dupont11763 STUDY INFORMATION SubstanceTested ENN SsmA onms/Codes-- : ---- + H-25509 Submitters Notebook Numberts): NN Haskell Number: 25509 CAS Registry Num(bi er: sms -- Sponsor: E.L du Pont de Nemours and Company Wilmington, Delaware 19898 USA. -- StudyInitiatedCompleted; 22-Nov-2002/ (sec report cover page) ~ -YY Company Sanitized. Doss not caesar era car F2-8D2-u5D5ya0y9SS:utRudedypyieinantMMeoadll-eeDoRRseaetssDsermal Toricity --_ DDuiPonet 117s63 STUDY PERSONNEL Study Director: Carol Finlay, B.A. Management: Scott E. Loveless, Ph.D. Primary Technician: Janine A. Britton, B.S. Clinical Pathologist: Nancy E. Everds, D.V-M. Management: Steven R. Frame, D.V.M., Ph.D. Anatomic Pathologist: John F. Hansen, D.V.M., Ph.D. Peter C. Mann, D.V.M. Management: Peer Review Anatomic Pathologist: Steven R. Frame, D.V.M., PhD. John F. Hansen, D.V.M., Ph.D. Statistical Analysis: John W. Green, Ph.D. Management: Janice L. Connell, M.S., B.A., C.LH Toxicology Report Preparation: Brenda Tiffin Cecilia Rowe Kee, B.S. Management: Nancy. Selzer, M.S. --~ Laboratory Veterinarian: Thomas W. Mayer, D.V.M., AC.LAM. -- _-- m Company Sanitized. Doss not contain TSCA CBI Tos F2-82-5D5a0y9:StRuedpyeiantMeeda-lDeoeRsaetsDermal Toxicity PN DDuPw ont 1g 1763 SUMMARY `dTehremoabljeecxtpiovseuorfe.thiTshesttuedsyt swuabssttaondceetwearmsianpeptlhieedpottoentthieaslhtaovxeidc,itiynotafctH-s2ki5n5o0f9mfaollelowing repeated oCfrl1:0CmDal(eSDra)tIsGwSerBeRtrreatastefdorde6rhmoaulrlsy/wdiatyhf5o,r5a0p,praonxdim5a0t0elmyg/2k8g/cdonasyeHc-u2ti5v5e09d.aysA. cTohnrteroelggrroouupps odufr1i0ngmathleesrtautdsyw.asBlsoiomdilsaarlmyplteresatfeodr wbiltohodmifnleuorrailneoilw.erFeoocodllceocntsedumopntiteosnt wdaayssd0e,t7e,rm1i4n,e2d1,weekly and day 27. 28. ABlllooradtsanudnduerriwneenstamnpelcersopwseyrfeorcoglrloescsteadndfomricclrionisccaolppiactphaotlhooglyogpircailoteorvaslaucartiifoinc.e on test dTohseargee.weNreoncolienifcfaelctssiognnsbaotdtryibwuetiagbhlte,tofosoydstceomniscumtpoxtiicoint,y ofcocoudrreefdf.iciency, or mortality at any Erythema (score of1 or 2) observed sporadically was considered not test substance-related. c`Soommpeoufnludo.rinTehiwsasfipnrdeisnegnwtaisn tchoensdiadyer2e7dbtlroeoadt,meinntd-ircealtaitnegdebxuptosnoutreadtvoearsfel.uoride-containing Dcoirfrfeelraetnicveesgrinososrgoranmiwceriogshctospwiecrleesniootnsp.reGsreontssinobasdeorsvaetrieosnpsoannsde fmaischrioosncoapnidcftihenrdeiwnegsroecncour --~ stphoenrtainnecoiudselnyceinorratsseovfertihtiy.s strain and age and were not present in adose response fashion in `TTrheeartemewnetr-erenloatterdeamtimledntd-ercerleataesdescihnansgeersuminchheomleasttoelroogliicn orratcsotargeualtaetdiaotn 5p0a0rammge/tkergs/dianythweerraets. ctroenastieddearted50t0o bmeg/pkotge/ndtaiyalwleyraedvceornssei.deTrreedattmoebnet-nroenl-aatdevdermsiel.d dTehcerreeasweesrienntorisgtlaytciesrtiidceaslliyn rats significant ats dosed or treatment-related changes in urinalysis parameters. Urine fluoride was at 50 or 500 mg/kg/day; this change indicated exposure to and metabolism increased ofa in- fluoride-containing compound. but non-adverse. Urine fluoride changes were considered to be treatment-related Bobasseerdveodn etfhfeecptrelseevenlce(oNfOdEeLc)r*eafsoerdthcehodleersmtaelrolexipnossuormeeofrHat-s2t5re5a0te9d autnd5e0r0tmhge/ckogn/ddiatyi,ontshoefntoh-is study was 50 mg/kg/day for male rats --_ a TtthhheeeUe.NsStO.sEuELbPsAftoar(n1ch9ei8w5es)rtaeundndyoittoddteehtfeecitnneoedd-.oabsTsthehrsev,ahibfgiohr-eatsdhtivsdeosrstseu-doayft,fwhcheticlNhevOeoElxiL(cNoiOslcAoqgEuiLicv)aaallyenidtmepftooirnttehadenNbtyOeftEfheLectEsausardoteprfeiianbneudUibnayibtooln (1994). Te. `Lompany Sanitized. Doss not contain TSCA CBI ZD2Ho-82-y5D5Sa0yu9:SdtRuyedpyieinsntMMeadll-eeDaRRsaeetsDsermal Toxicity -- ODudPonet 117s63 INTRODUCTION `dTehremepaulrlpyofsoeroafptphriosxismtautdeylwya2s8tdoayesv.aluTahtiestshteutdoyxiwcaistyionfteHn-d2e5d5t0o9prionvmiadleeirnastisghwthteonthaedmpionsisisbtleered lhiummitaend hpeearlitohdohfaizamreds.associated with repeated dermal exposures to the fest substance over a AderrmaangleafpipnldiicnagtisotnusdoyfwaHs-2c5o5n0d9ucatteddostoagaeisdoifn0d,os1a0g,e1s0e0l,ecotrio1n0.00Grmogu/pksgofof2r 6maholuerrsatfsorreceived consecutive days. No adverse clinical signs or body weight losses occurred. 0Dfos5a0g0emsgo/fk0g,/d5,ay50w,aasndsel5e0c0temdgb/ekcga/udsaeyiwteisregrseealteecrttedhafnorthtehele2v8e-ldtaoywshtiudcyh. hTuhmeanhsigmhadyosbee level potentially exposed to the test substance. STUDY DESIGN Group Number/Group Dosage (mg/kg) -- T 10 0 m 10 5 v 10 50 vi 10 500 MATERIALS AND METHODS A. Test Guidelines Except as noted below, the study design complies with the following test guidelines: + OPrfoftiecceotfioPnreAvgeenntciyon(,EPPeAs)ti(c1i9d9e8s).andOPTPoxTiSc 8S7u0b.st3a2n0c0e2s1(/O2P8P-DTaSy)DUe.rSm.aElnvTioxriocnimteyn.taHlealth Effects Test Guidelines. + DOrogsaeniDseartmiaonl fToorxiEcciotyn:om2i1c/C2o8--ODpaeyrSattuidoyn. aGnudidDeelvienleofpomreTnetst(iOnEgoCfD)Ch(e1m9i8c1a)l.s.410 Repeated Obenclayumsealmealraetssawreertehetrmeaotreed.seTnhsiistievxecseepxtitoontdhiedtnooxticaoflfoegcitcatlheefofbejcetcstiovfefslouorrvianlaitdeidtyteosft the study substances such as H-25509. --_ Company Sanitized. Doesnotcontain TSCA CBI - es BH2l--2D5ya50y9SS:utRudedpyMeianteMeadrl-eDoeRsaetsDermal Toxicity DDuuopownit1i1i76e3 --_ `aTphperolxaibomraatteolryy c1.l5osheodurosnotnestthdaatyda1y0. bTehciasuseexocfeipntcilonemdeindtnowteaatfhfeecrt.tTheheobrjaetcstiwveerseoerxvpaolsideidtyfoorf the study because the test guidelines say the exposure period can be 21 days. B. TestSubstance `sTuhbesttaesntcesuabpspteaancree,dHt-o2b5e50st9a,blweausnsdueprptlhieedcobnyditthieosnpsoofntsohreasstauddya.rkNboreovwindegnrcoeuonfdinssotliadb.iliTthye, test such as a change in color or physical state, was observed. Tskhien.teTsthessuebsptaasntcees wwaesremoniosttaennaeldyzweidthfomrinstearbailliotiylotro hfoomromgeantehiitcyk.pTahsteepbreofcoerdeuarpepsliucsaetdiownetroethe bapeplliiecvaetdioton.reAslullotfitnhaepatsesttestuhbasttwaanscehaodmmoigniesnteeoruesd waansd satsasbulemebdettwoebeenapvraeiplaarbalteiofonraanbdsorption. For the dosage. purposesofthis study, all toxic effects were reported as a functionofthe administered C. Test Species --~ OOcntoNboevre3m,b2e0r0219w,e2r0e02r,ec4e5ivmeadlferCormlC:hCaDrl(esSDR)iIvGerS LBaRborraattso,riweist,hIannc.asRsailgeniegdh,biNrotrhtdhatCearooflina. `aTvhaeilCarblle:CfDr*o(mStDh)eIlGiSterBatRurer,attwheassuspeplleicetre,dabnedcparuesveieoxutsesntsuidvieesbaccokngdruocutnedd iatnfHoarsmkaetliloLnaibsoratory. "This strain disease. is also considered suitable relative to hardiness and low incidenceof spontaneous D. Animal Husbandry 1. Housing Rats were housed singly in stainless steel, wire-mesh cages suspended above cage boards. 2. Environmental Conditions AAnniimmaall rroooommss wweerree maratiinfitcaiianlleydialtluamtienmapteedra(tfulrueoroefsc1e9nt-2l5ighCt)anodn aanrealpatpirvoexhiummaitdei1t2yo-hfou3r0-70% dluirghatt/idoanrktocyhcalvee. aEdxvceurrsseiloynasffoeucttseiddetohfetvhaelisdeitryaonfgtehsewestruedyo.finsufficient magnitude and/or 3. Feed and Water ~ `Tap water was LabDiet 5002 provided ad libitum. PMI" Nutrition meal was available ad libitum except International, when the rats LLC were Certified fasted. Rodent eeTrteeeet Eompany sanitized. Does not contain Tsca car BH2o-82-5Dy5a0y9S:StuRueddpyeoiantMMeadel-DeRoRseaetsDsermal Toxicity --~ 4. Mdentification DDiuPmonit 11763 Poruitosridteooafsistisgcnamgeen.t Atfotgerroaupsss,igenamcehntrattowgarsoutpesm,poeraacrhilryatiwdeanstiafsiseidgbnyedaacuangieqcuaerd6-adfifgiixteHdatsoketlhel aanniimmaall nnuummbbeerr waenrdeantaitntdoioveiddouanltchaegteaiilodfenetaifcihcartaito.n nTuhmebienrf.orTmhateiloansto3n dtihgeitcsaogfetlhaebeHlassiknecllluded the Haskell animal number and the individual identification number assigned to cach ra. 5. Health Monitoring Program AfosllsopweicinfgiperdoicnedthuereHsasakreelpleLrafboorrmaetdorpyerainoidimcaalllhyeatlotehnasnudreetnhvaitrcoonmnetnatmailnamnotniltevoerlisnagrperboeglroawm., the those that would be expected to impact the scientific integrityof the study: + Water samples are analyzed and other contaminants. for total bacterial counts, and the presenceofcoliforms, lead, + Feed samples are analyzed for total bacterial, spore, and fungal counts. + Samples fromfreshlywashed by the cagewashers. cages and cage racks are analyzed to ensure adequate sanitation ~ Creerqtuiifrieemdeanntismaanldfneoetd tios uesxecde,egdusatraatnetdemeadxbiymtuhemmcaonnucfeancttruarteirontsoomfekeetyscpeocnitfaimeidnanunttrsi,tiionncalluding sppreecsiefniceed ohfeathveysemectoanltsa,maifnlaantotxsinb,eclholwortihneamteadxhiymdruomcacrobnocnesn,traantdioonrgstaantoepdhobsyphtahetemsa.nuTfahceturer would not be expected to impact the integrityofthe study. `lTahbeoraantiomraylanheiamlatlhvaentedriennavriiarno.nmeEnvtaalluamtoinoinotofrtihnegsperdoagtraadmidisnaodtmiinndiisctaetreeadnbyyctohnediattitoennsditnhgat affected the validityofthe study. E. Pretest Period U3ptoimneasrrainvdaleaxtamHaisnkeedlldaLialbyofroartoarnyy,ctlhienircaatlslywearpepaqrueanrtasnitginnsedoffdoris6 edaaysso.re Tinhjeurrya.ts were weighed Oqunartahnetibnaeseosonfteasctcdeapyta0blbey bthoedylawbeoirgathotrgyaainnismaanldvceltienriicnaalrisaing'nss,detshiegnreaets. were released from F. Assignment to Groups and Study Start cFloirntiycarlatssigwnesroefdsiesleecatseed ofrorisnjtuurdyy, uasnedoanbtohdeybwaesiesgohftawdieqtuhai=tne2b0o%doyfwtehieghmtegaanin,wiftrheinedaomsexf.roTmhe ~~ sthealtecttheedrerawtesrweerneodsitavtiidsetdicablylycosimgpnuitfeircainztedd,ifsfterraetnicfieesdarmaondnogmigzraotuipobnoidnytow4eiggrhotupmseaonfs.10 rats, so er TTT eee Eompany Sanitized. Doesnotcontain Tse cay H2-82-5D5a0y9:StRuedpyeiantMead-lDeoRsaetsDermal Toricity DuPont 11763 --_ Dose administration 8 weeksofage. with H-25509beganon testday 0 when the rats were approximately G. Test Substance Preparation and Administration `eTnhoeudgohsimnignepraaslteosilwteorefoprrmepaapraesdtej.ustWaprtieorr wtoatsrneoattmuesnetdbbyecmaiuxsiengittdhiedtnesottssuubffsitcainecnetlwyimtohijsutsetn the test substance. Ofrnomthtehdeabyacprkiaorndtottruhnekf.irsOtntrceaactmhednat,yotfhetfrueraotfmeenatc,hthreatrawtasswoclroesepllyassthicavceoldltaorsedxuproisnegtthheeskin aerxepaostuorbeepterreiaotdedtowapsremvaenrtkeidngoesnttihoenobafctkheofteesatcshubrsattawnictehaanwdatdeirs-riunptsioolnuobfltehmearwkrearp.piTnhges.raTtshe dapopsreodxaitma0toerly50e0qumagl/tkog/1d0a%yohfatdhea ttorteaaltmbeondtyasruerafaofc3e 7arceamf.oTr hraets3i7n tchme?2t0r0eattom3e0nt0agreraanigse of bsmoadlylwteoicgohtvse.r 3T7hecmv.oluTmheeoftrteeasttmesnutbsatraenacfeorfotrhetshee rraattss dwoassed12a.t255 cornr5,0omrg3/.k3g%/odfatyhweastoftaolobody sfuorrfmacae.paTstheeaanldiqaupoptolifetdeesvtesnulbystaanndcaesdtehsiinglnyatasedpfoosrsaibnleantoimtahle wteastssmitoei.stTehneedtewsittshubmsitnaenrcaelwoialsto cmoovreeretdhawnithlaay2e-rps)lyanpdorsoeulsfg-aaduhzeesdivreesbsainndgagfeo.llEoawecdhbdyaysoufccdeosssiinvge,ltahyeercsoonftrsotlrertactsh rgeacuezieve(dnothe --_ same volumeofmineral oil as the high-dose treatment approximately the same time each day. group. The rats were treated at `bGordoyupwseiogfht1.0 mTahleerraattsswweerreettrreeaatteeddfaotrdaopspargoexsiomfa0te,l5y,2580,coonrs5ec0u0tmivgeodfaytse.st Tsuhbesatmanocuenpteorftkge.st mseubasstuarnecmeenneteded to treat cach rat was based on the most recently determined body weight `wTrhaepepxipnogssuwreerpeerrieomdowvaesd aapnpdrtohxeimtaesttelsiyte6whiopuresd. wiAtfhtearwtehte pexappoesrutroewpeelraiondd,wtahsehceoldlwaristhansdoap taintdswcaargme.taCponwattreorl.anTihmealtsesrtescietieovfedcathcehsraatmewawsasthhiennggetnetclhynipqautteeadsdtrhyeatnrdeattheed arantimwaalss.retumed Ofrnomtestthedarayts10a,fttehrealpapbroorxaitmoartyecllyos1e.d5 dhuouertsoofienxcploesmuenrte;weather. The test substance was removed e`fTfheectasn.imTahles wenetriereraersehaavtehadtawsanseeordiegdindaulrliynsghtahveedst(uidnycltuodfiancgiltihteatuentthreeaetveadlucaotnitornoolfdskeirn)mawals reshaved. The animals were shaved only afer an evaluation. H. Body Weights --~ All rats were weighed at 3-4 day intervals during the study. TTI -- ie Company Sanitized. Does not contain Tara cay H2-82-5D5a0y9S:tRudeypeiantMel-eDeoRRsaetsDermal Tosicity ~ IL Food Consumption and Food Efficiency w DuPoe nt 11e 763 Tbehgeinanmionugnatnodfenfodoodfctohneswuemeekd abnydeasucbhtrraatctwiansg tdheetefrinmailnweediwgehetkalnydbtyheweaimgohuinntgoefacsphiflleaegdeerfratomthe cthoensfuemedpetridounroivnegrtthheewweeeekkfwraosm dteheteimniitnieald.weiFghrto.mFthreomfotohdecseonmseuamsputrieomnenatnsd,bmoedaynwdeaiiglhytfdoaotda, `mean daily food efficiency for each group was calculated. J. Mortality and Clinical Observations `tThheedraatys thweerleabcohreatcokreydcolnocseedfborecmaourtsaeloiftiyncanldemfeonr tsiwgenastofheirl.lneTshse,yinwjeurrey,cohrecakbendortmwailcebedhaailvyioalrlon other days. `sTuhbestraantcsew.erTeheobDsrearivzeedSfcoarlceliwnaicsalusseidgntsoo fsctoorxeicsiktiynainridtadteiornm.alAedfjfaeccetsntafatreerarseomfovuantlroefattheed stkeistn `were used for comparison. The rats were also observed for clinical signs ateachweighing. K. Total Fluorine and Perfluorooctanoic Acid Level Evaluations ~ Btelsotoddaywsa0s,c7o,ll1e4c,t2e1d,iantnodE2D7 TapAprtouxbiemsaftreolmy tohneeohrobiutralafstienrursoemfotvhaeloffirsth5e atetsst isnubesatcahncge.rouTphoen bblyouosdinwgasa rWeifcrkigbeorlatdedt.orcThhecotmobtaulstfliuoonrimneetchoontdefnotollfotwheeddbayya2na7lybsliosodwistahmaplfelsuowraidsedfeotnesremliencetdive Jelaeccktsroodne.LabTohreatroermy,aiDneienpgwsaatmeprl,eNsewwerJeernsoety.analyzed. Fluorine blood analysis was performed at EAdDdTiAti.onPallabslmoaodwawsasprceoplalercetdedanfdrowimllthbeevsetnoarecdavfaroozfeanllatr-a8s0atCnteoc-r2op0syC iunnttoilaatnuableyzceodntfaoirning acosnucpepnltermateinotnaolfrpepeorrftl.uorooctanoic acid (PFOA). The resultsofthe analysis will be presented in L. Clinical Pathology Evaluation `AThcelidnaiycablepfaotrheocloolglyecetviaolnouaftisoanmpwlaesscfoonrdtuhcetecdlionincaalllpaattsho2l8ogdyayevsaalufaetrioinn,ittihateiaonnoifmtalhse wsetrudey. purlianceedwainsmceotllaebcotleidsfmrcoamgeesa.chTahneismeala.niBmallosodwesraempflaesstefdoorvheemmniagthotlo(gaypparnodxicmlaintieclayl 1c6hehmoiusrtsr)yand mcaerabsounredmieoxnitdsewaenresethceoslilae.cteBdlofordomstahmeploerbsitfaolr scionaugsuolfateiaocnhpaarnaimmeatlewrhsiwleertehecoalnliemcatledwaatssaucnrdifeirce -- fanreosmthtehseiaa.bdAodmdiintailonvalenbalocoadvaocoflleeaccthedafnriommalthwehivleenathceavaaniwmaasl wplaasceudndienracsaerrbuomn dtuiboex,idperocessed to serum, and frozen at -80C. Bone marrow smears were prepared at sacrifice from all --T-- TT reEer------s BompanySaniized. Doesnotcontain sca cay H2--2D5a50y9:StRuedpyeisntMeadl-eDoRsaetsDermal Toxicity DouPvonet11n763s -- snuercveisvsianrgy atnoismuaplpso.rtBeoxnpeermiamrerntoawlsfmienadirnsgsw.ere stained with Wright's tain, but analysis was not 1. Hematology and Coagulation bBllooooddcsoaumnptsl,esinwcelruedienvgalruetaitceudlofcoyrteqsu,alwietryebydevtiesruamlineexdamoinnaatBiaoyneprrioArdtvoiaana1l2y0sihse.maCtoomlpolgeyte asnmaelayrzserfroormdealtlearnmiimnaeldsfwreormemeicxraomsicnoepdicmiecvraolsucaotpiiocnoaflltyhfeorbcloonofdirsmmeaatri.onoWfriaguhtt-osmtaatiendedrebsluoltosd parnedpeavraeldufatrioomnoefaccehllaunliamralmournpdheorlgoogiyn.g Blood smears, stained with a hematology evaluation but new methylene blue, were not needed for were examination. Coagulation times were determined on a Sysmex CA-1000 Coagulation Analyzer. The following hematology and coagulation parameters were determined: red blood cell count hemoglobin platelet count white blood cell count hematocrit `mean corpuscular volume differential white blood cell count microscopic blood smear examination `mean corpuscular hemoglobin `mean corpuscular hemoglobin concentration --_ red cell distribution width absolute reticulocyte count pacrtoitvhartoemdbpianrtitailmethromboplastin time 2. Clinical Chemistry S71e7rucmlincilcianliccahlecmhiesmtirsytranyalpyazrearm.etPelrasswmearefldueotriedremicnonecdeontnraatRiooncsheweDrieagdneotsetrimcisn(eBdMuCs)/iHniagtapchhiil2 `PH meter and a fluoride-selective electrode. "The following clinical chemistry parameters were determined: aspartate aminotransferase alanine aminotransferase sorbitol dehydrogenase alkaline phosphatase: total bilirubin urea nitrogen creatinine cholesterol triglycerides pe glucose: total protein albumin globulin calcium isnoodriguamnic phosphorus potassium chloride fluoride* a Fluoride determiwnasaantailyozend on EDTA plasma TT Company Sanltizod, Does notcontain TSCA CBI ZD2Hu8-2DS5a5uy09hS:RyuedipyenaintMeMadaleDeoRRsaeetsDsermal Toxicity --~ 3. Urinalysis oDwupeonnt. 11763 Urine volume and appearance (quality, color, and clarity) were measured and evaluated visually, rAeustpoecmtaitveeldy.UrUirnienCehceomnissttitruyenatnsalwyezerre. seUmrii-nqeuapnrtoitteaitniwvealsy mmeeaassuurreedd oonn aa RBoacyhere CDliiangintoeskticAstlasTM (AdBvMaCn/cHeidtaOcshmiom7e1t7ercl3i9ni0c0a.l cUhreimniestfrluyoarniadleyczoenrc.enUtrrianteioonssmowlearleitdyetwearsmidneetderumsiinnegdaupsihnigl2anpH cmoentceerntarnadtaionf)l.uor`iSdeed-ismeelnetcstifvreoemleacltlruordie,neasnpdetcoitmalenusriwneerfelueovraildueastwedermeiccraolsccuolpaitceadll(yv.olume x The following urinalysis parameters were determined: quality color clarity volume osmolality pH glucose ketone bilirubin blood urobilinogen fluoride protein microscopic urine sediment examination a Fluoride determination was analyzed rom rine with EDTA added. -- M. Anatomic Pathology Evaluations `Rwaatsspweerrfeorfmaestdedonafttheer r3apts.mf.ololnowtihnegatfhteefmionaolncbleifniocraeltphaetirhoslcohgeyduelvealduasatciroinf.iceA.llAraftisnaslacsraicfriicfeidceby daneessitghnesuinadearnwdeenxtsaanggruoisnsatainodn.miTchroesocrodpeircoefvaslaucaritfiiocne. wRaastsrawnedroemeuatmhoannagtiazlledtrbeyatcmaernbtognrdoiuopxs.ide `The following tissues were collected from the ras. Digestive System liver heCaarrdtiovascular System esophagus stomach aorta duodenum jejunum Hematopoietic System spleen ileum thymus cecum colon mmeasnednitbeurliacrllyymmpphhnnooddee rectum salivary glands bone marrow* pancreas Endocrine System rinary System ptihtyuriotiadryglgalnadnd ~ kuirdinnearyysbladder padarreantahlyrgoliadngdlsands Mskueslceutlalosmkueslcetlael System fsteemrunru/mknee joint Reproductive System testes perpoisdtiadtyemides seminal vesicles Miscellaneous skin eyes (including optic nerve) gross observations" - BompanySanitized. Doss not contain Tr CBI A H2-82-5D5a0y9S:tuRdeypeiantMeadR-lDeoRsae etDsermal Toxicity -- Rluensgpsiratory SystemNervboruasinS(ycsetreebmral cortex, cerebellar cortex, trachea `medulla/pons) nasal tissue larynx spinlaulmcboarrd)(cervical, mid-thoracic, pharynx sciatic nerve DDuuPomnt 11763 a BGroonsesmoabsrerrovwatwiaosnscomlaldeectaetdnweictrhotphseyffeomruwrhiacnhd shiesrtuompa,thology is not appropriate (e8, Mud, ruffed fur, and missing anatomicparts)were genenrotacolllelcteyd. All tissues were placed in an appropriate fixative. `tThhyemurast,sbsraacirni,fiscpeldeebny,dheesairtg,ntheastdest,heanfdolelpoiwdiindgymoirdgeasn.s wReeilgahteidve:orligvaenr,wkeiidgnhetyss,(paedrrceennatlogflfainndasl, nbeocdryopwseiygwhet;rerautsioedtoinbrtahienawsesiegshstm)enwteorfe ocarlgcaunlawteedi.ghtFicnhaalnbgoesd.y weights determinedjust prior to Asllildetsi,sssuteasinceodllweictthedhfermoamtraotxs yinlatinhdne heiogsihn-,doasnadgeexaanmdicnoendtrmoilcrgorsocuoppsicwaelrlye.fuMrothsetr pgrrooscseslseesdiotnos eavnadluaantyeaddmdiictrioonsacloptiacragleltyo.rgSaenlsecftreodmgrraotsssionbtsheervlaotwi-onasndfoirnwtheircmehdaiamtiec-rdoosscaogpeigcrdoiuapgsnowesries.would ~ ndeoftobremiatdideistoifvteh(ee.g.t,eetohs,tetooacr,thtraiilt,iso,rpcoadropdienrnmaa)tiwtesr,e csharvoendi,cbtuatilwdeerremantoittipsr,occaelscsueludsf,oarnd microscopic evaluation. -- Company Sanitized. Does not contain TSCA CBI TT ---- ZD0 H2-8y2DS5a5u0y9dS:yuRdiynieMnMapaleDeoRsetaaDssertmaelTodxici:ty Doupwonnt11s763 ~~ N. Statistical Analyses Significancewas judged at p < 0.05. BBoocddyyhWeeiiggehnt Gnain Food Efficiency Organ Weight Clinical Pathology SIncaidelnce of Cll ee Incidence of Deal Effects Preliminary Tes Fogrenet nViectthsodonoftSa|teUsignraifielliAnmdiinny TT Tetraitotwdend?? |eSequoentrialespeTeaars a|rEpiminIary esDtfs forr Et oShnaipiorgountWi lk test for Levene'vas tor S`htoampoigernoe-iWtiyelasknd5 for One-way analysisof |Kruskal-Wallis cs |Dvuarninanecee fsolloowed with | efolslowed with Dunn's One-way analysis of Kruskal-Wallis -test"? |1variaencre"eey sfotlloewed with | feoslltowed with Dunn'iss Cochran-Armitage test for trendor -- a sPiignriifieanc,omparisons and asocated preliminary ets wer nly conducted fh st fo lackof rnd was btwahs usSehd.opiIroh-eWiSlhkafpeistrw-aWsiokttessitgnwiafsicsaingtnibfuitcaLnte,vKernuesktaelstWwalslsgaesitnwass,ForlolbouwsedtbvyerDsuinono'fsDtuotm. mett 4 WBoIfohtnnehfenleintrnhoceinidnerdcneiccvoeoidrswudaatelsdoonvboaswtleaesrsi.vgauntFsieifodoi.cnacanxtas,mbpruletec,aorsfdiegidnliifaisrcbbaienntinlwgaaclskeorsfefptiohtratnoecdcuearsrs<e0di.,1t,vha0e.ln0uF5,icswhlaecsrl'aastsEiexoanfcostratwmeeyrsect'uplewraifttohiraomends perormed with thatbilibindaa. --_ - oo contain'TsCACE! amSeny 2H6:-25D5a0y9S:tRuedpyeiantMeadelDeRoRseaetsDermal Toxiity -- RESULTS AND DISCUSSION DDwuPaotnti11e763 In-Life Toxicology A. Mean Body Weights and Body Weight Gains (Tables 1-2, Figure 1, Appendix A) NMeoaenffbecotdsyownebigohdtygwaeiinghwtassoscicgunrirfiecdanitnlayndyecgrreoauspeodfrcaotmspadroesdedtowictohnttrhoel tienstthseub5s0t0anmcge/,kHg-/2d5a5y09. `bgercoauupsdeuritionngltyhoecicnutrerrveadladtaoyne24t-i2m7e.poHionwteavnedr,wetihgishtdegcarienawseaswanostcsoingsniidfeircaendtlnyond-eacdrveearsseed over the courseofthe study. B. Food Consumption and (Tables 3-4, Appendix B) Food Efficiency --~ No test effects on food substance. consumption or food efficiency occurred in any groupofrats dosed with the C. Clinical Observations, (Tables 5-7, Appendices Dermal C-E) Evaluations, and Survival Nswoolclliennicfaalcesiogbnsseartvterdibiuntabboltehtocosnytsrtoelmriactstoaxnidcirtaytsoctcrueratreedd.wiOtchutlhaertoerstnsausbalstdainsccehawregreeand considered to be loss was present due to thewrapping in single rats in the collar application procedure. 50 mg/kg/day group and were Superficial considered wounds or hair incidental and not - agdrioruepctwaesffencottofotbshervteesdtisnubasntyanrcaet,s inRetrdeaotreadl adtis5c0h0armgge/kwga/sdoabysaenrdv,edthienre1forraet,iwnatshen5ot0 cmogn/skigd/edraeyd to in btheet5re0a0tmmegn/t-krge/ldataeyd.groTuhpewoabssecrovnastiidoenroefddtaorbkeeayereisnul2t rats in the 50 mg/kg/day oforbital sinus bleeding. group and 1 rat cEornystihdeemraed(sncootrteoobfe1toesrt2s)ubwsatsanocbes-errevlaetdeidnbseocamuesreiattswiansthaels5o0ombgs/ekrgv/eddaiyn gcroonturpolanradtsi,s No deaths occurred. --_ jz0d. 00%"noteinTSCACS compen! ee e T ieee BDF2-5y2-5SD5au0y9bS:ytRuiedpyneiMantiMeladl-eeDRoRsaeetssDermal Toxicity --~ D. Blood Fluorine Analysis (Appendix F) 000000 DDwuPeomntn-1r17e63 eSxopmoesufrleuotroianefwluaosripdree-sceonnttainintihneg dcaoym2po7ubnldo.odTfhriosmfirnatdsindgosweads wciotnhsitdheerteedsttsoubbesttarnecaet,meinntdircealtaitnegd bquuatnntoiftiacdavteirosne(.LOAQll).rat`sThtereraattesdtartea5temdg/atkg5/0dmagy/hkagdhfalduolreivneelsleovfelfsluboerlionewrtahnegliinmgitforfom 1.14 to F1l.u8o3rpipnme.levTehles orfat0s.5tr8eaotre1d.5at7p50p0mmgi/nk2g/cdonatyrohladraftslucoarninneotlebveelesxprlaanigniendg. frAlolm v5a.l0u7estofo1r9.t3h5e ppm. remaining control rats were below the LOQ. E. In-Life Conclusions U50n0demrg/tkheg/cdonadyiftoironmsaolfethriatsssbtausdeyd, othnetnhoe-aobbsseenrcveedo-faaddvveerrssee-eofrfctetstlesvueblstfaonrcien-lrifeelaptaerdamefefteectrss. was Clinical Pathology Evaluations A. Hematology -- (Table 8, Appendix G) `stTahteirsetiwcealrley nsiogntirfeiactamnetntc-hraenlgaetsedinchmaenagenshienmahtemoaltooglyopgaircapmaertaemrestweerrseincomnasliederartes.d tTohbee fuonlrleolawtiendg 0 treatment and non-adverse because they did not occur in a dose-related pattern: + Minimally decreased red blood cell counts in males treated at 50 mg/kg/day. Minimally increased mean cell hemoglobin concentration in males dosed with 5 mg/kg/day. B. Coagulation (Table 9, Appendix G) Tmhaelreerawtes.re no treatment-related or statistically significant changes in coagulation parameters in C. Clinical Chemistry (Table 10, Appendix G) Cholesterol was mildly decreased was 71%ofcontrol group mean). in some male rats treated at Individual concentrationsof 500 mg/kg/day rats treated at (mean cholesterol 500 mg/kg/day ~ ranged from 27-69 mg/dL, while cholesterol concentrations in control rats varied over a smaller Company Sanltized. Does not contain TSCA CBI H2-82-5D5a0y9S:tuRdeypeiantMe eadl-Deoe RsaetsDermal Toxicity wDupeontn1176s3 --_ range (47-65 adverse. mg/dL). This change was considered to be treatment-related, and potentially `cTornisgildyecrereiddetso wbeerteremaitlmdelnty-dreelcarteeads.edHionwemvaleer,ramtisltdrleyatdeedcartea5s0e0dmtgr/igklgy/cdearyi.desThariesncohtaansgseocwiaasted with toxic events, so this change was considered to be non-adverse. `fTohlelroewwinegrestnatoisottihcealrltyrseiagtnmiefnitc-arntelcahteadngcehainngmeesainn cclliinniiccaall cchheemmiissttrryy ppaarraammeetteerrss winamsacloensriatdse.reTdheto be unrelated to treatment and non-adverse because it did not occur in a dose-related pattern: + Increased glucose in male ratstreatedat 50 mg/kg/day D. Urinalysis (Table 11, Appendix G) There were male rats. no statistically significant ortreatment. related changes in urinalysis parameters in E. Urine and Plasma Fluoride _ Uorri5n0e0fmlgua/rkigd/ed(aoyta(lTefxltuoTraibdeleexI)c.reItnecdredausreidnguroivneernfilguhotrifdaesti)ndwiacsatienscerxepasoesdurien mtoalaensd tmreetaatbedolaits5m0 ofa fluoride-containing compound. `Text Table I: Mean urine fluoride for males Dose (mg/kg) Parameter (units) UFLU (ug) 0 5 50 500 95 133 23.0 1472 %ofcontrol mean NA 242% 1549% `Statistical significance is indicated byboldialcied type. F. Clinical Pathology Conclusions Itrnicgloynccelruisdieosn;,dedcerremaasleddocshionlgesotfer5o0l0wmags/kcgon/sdiadyerceadusteodbmeiplodtednetciraelalsyeasdvienrssee.ruUmrcihnoelefsltueorroildeawndas mienctraebaosleidsimnomfalaefslutorreiadtee-dcaotnt5a0inoirn5g0c0ommgp/okugn/dd.ay;Urtihnies cflhuaonrgiedeicndhiacnagteesd weexproescuornesitdoearnedd to be treatment-related but non-adverse. `tThheerneof-oorbes,eurvnedde-radtvheercsoen-dciftfieocntsolefvtehliwsasstu5d0y magn/dkgfo/rdathyefcolrinmiaclale praattsh,oblaosgeydpaornapmreetseernscmeeoafsured, ~ decreased cholesterol in some rats treated at S00 mg/kg/day. i ompany Sanitized. Doesnot contain vera ray BH2-8l2-5D5ua0y9S;StuRudedpyyeiabntMMeadal-eDloResaetlsDsermal Toxicity --~ Anatomic Pathology Evaluations A Mortality There were no early deaths. DDwuePomnit i117e63 B. Organ Weights (Table 12, Appendix H) `hTihgehemretahnanabtshoelcuotnetraonld. rTelhaetrievewweerieghntosocofrtrheleatliivveergraonsdskoirdmniecyrsowsecroepisctalteisstiiocnaslliynseiigtnhiefrictahnetllyiver ogrrokuipds.neyT,haunsd, thhieghoerrgmaneawneiwgehitghcthsaonfgteshweelrievenroatnpdrkesiednnteyinweardeosceonrseisdpeornesdetfoabsehisopnuarciroousssatnhde not adverse. C. Gross Observations (Table 13, Appendix I) Awlelregrnoostsporbesseernvtatiinoansdonsoeterdesaproenksneofwasnhitoonocincueritshpeornitnacnicdoeunscleyoirnsreavtesroiftyt.his strain and age and D. Microscopic Findings (Table 14, Appendix I) Aalgle maincdrwosecroepnioctopbrseesrevnattiionnasdnoosteedreasrpeoknnseowfnasthoiooncciunreistphoenrtiannceioduesnlcyeionrrsaetvsoerfittyh.is strain and E. Anatomic Pathology Conclusions `Under the conditions of this study, the no-observed-effect level for pathology was 500 mg/kg. CONCLUSIONS Nfoooddecaotnhssuomcpctuirorne,dfdouordinegfftihceiesntcuyd,y.cliNniocaaldsviegrnsse, toerstdesrubmsatlanicmei-trateiloantewdeerfefescetesnoinnbmoadlyewreaitsghtth,at rweeciegihvteddiafpfperreonxciemsa,tgerloyss28obaspeprlviactaitoinosn,saonfdHm-i2c5r5o0s9coappipclifeidnddianiglsywteortehecosnhsaivdeedreskditno. bOerngoann- awdevreersneo, aodcvceurrsespcohnatnagnecsouisnlhyeimnatraotls,ogayn,d/cooragwuelraetinoont, porreusreinntaliynsaidsopsareamreetseprosn.seMfialsdhiloyn.decTrheearseed ~~ acdhvoelresstee.roMliilndlsyomdeecrraetassdeodsterdigaltyc5e0ri0dmesykingr/adtsaydowsaesd caotn5s0i0demrge/dktgr/edaatmyewnte-rreelcaotnesdiadenrdepdotentially resist Company Sanltized. Does not contain TSCA CBI H2-8D2-5D5ua0y9S;StuRubdeypyeinantMMeadol-eeDokRsaeetssDermal Toxicity DDuPiout-m1176e3 -- ptrreeastemnecneto-frefllautoerdibnuetinnotnh-eaddvaeyr2se7.blIonocdreiansdeidcautreidneexfpluoosruirdee taot 5an0dorme5t0a0bomlgi/skmgo/fdaayfalnudortihdee- containing test substance and was considered treatment-related but not adverse. Bobasseerdveodn-etfhfeecptrelseevnelce(oNfOdeEcLr)eafsoerdthcehodleersmtearlolexipnossoumreeorfatHs-d2o5s5e0d9wuinthde5r0t0hemgc/okngd/idtaioyn,sothfetnhoi-s study was 50 mg/kg/day for male rats. RECORDS AND SAMPLE STORAGE Atlhle sdpaotnasaonr.d rLeacboorrdastofroyr-asnpaelcyitfiiccalorchsairtaec-tsepreciizfaitciornaswcdoantdau,cstuecdhbaystpheerssopnonneslorfiwlielslabnedreetqauiinpemdenbty records will be retained by the facility where the work was done. ALabsoarmaptloeroy,ftNheewatrekst,sDueblsatwaanrcee.wiSllpebceicmoelnlse(citefdapfpolriacracbhlie)v,e rpuarwpdoasteas, aanndd rtehteafiinneadlartepHoarstkewlilll be retained at Haskell Laboratory, Wilmington, Delaware. Newark, Delaware or at Iron Mountain Records Management, ~~ REFERENCES 1. `DWrialpeeyr,,NNe.wR.Yaonrdk.Smith, H. (1981). Applied Regression Analysis, 2" edition, pp 266-273. 2. Selwyn, MR. animal safety (1995). studies. The useoftrend tests to Journalofthe American determinae no-observable-effect level CollegeofToxicology 14(2), 158-168. in 3. Jonckheere, AR. (1954). Biometrika 41, 133-145. A distribution-free K-sample test against ordered alternatives. 4. LSteavteinstei,csH.(1.(1O9l6k0i)n., eRdo.)b,upspt 2te7s8t-f2o9r2e.quSatlaintfyoorfdvaUrniiavnecressi.tyCPornetssr,ibPuatlioonAslttoo.Probability and 5. sSahmapplierso,).$.B5.ioamnedtrWiiklak5,2,M.5B91.-(611916.5). An analysisofvariance test for normality (complete 6. Snedecor, 349-352. G.W The . and Iowa SCtoactheUrnainv,erWs.iGt.yP(r1e9s6s7,).AmSetast.istical Methods, 6 " edition, pp 246-2 48 an d ~~ a tTthhheeeUe.NsStO.sEEuLbPsfAtoa(n1cth9ei8sw5es)rtaeudnnyoittoddteehtfeecintneoed-d.oabssTtehrhuvesa,hbilfgeoh-eahsdtivsedrosssteue-dayft,iewtchhtieceNhvOetlEoxL(iNcioOslAcoqEguiLiav)lallayesnidtmeptfoirnttehadenNbtyOeftEfheLetEsausardforepbfeuiatenadbUlbneyiotno (1994) - BampanySanitzed. Dossnotcontain TSCA Cat B0 12.b52.y5D5sS0y9u:SitRyepienMsVtieie-DRoRssassDermal Toxic wDupoontw176s3 -- 7. Dunnett, C.W. (1964). New tables for `multiple comparisons with a control. Biometrics20, 482-491. 8. Dunnett, C.W. (1980). Pairwise multiple comparisons in the unequal variance case. J. Amer. Statist. Assoc. 75, 796-800. 9. Tamhane, A.C. (1979). Acomparisonofprocedures for `multiple comparisonofmeans with unequal variances. J. Amer. Statist. Assoc. 74, 471-480. 10. Kruskal, W.H. and Wallis, W.A. (1952). Useofranks in one-criterion analysisofvariance. J. Amer. Statist. Assoc. 47, 583-621. 11. Dunn, O.J. (1964). Multiple contrasts using rank sums. Technometrics 6,241-252. 12. Fisher, R.A. (1985). Statistical Methodsfor Research Workers, 13" edition. Haffner, New York. --_ --_ -_-- \contain TSCA CE. `Company Sanitized. Doss1 R12D82-5uD5a0yS9:SutRuedbpyeyiantMeMdl-ieDoeRseassDermal Toxicity wDuepoantn1763 TABLES ~ ~ Company sanitized. 000" contin scAce! a A H2-82-5D5a0y9S:tuRdeypienatMeaedl-eDRoRsaetsDermal Toxicity TABLES ABBREVIATIONS: EXPLANATORY NOTES Summary of Hematology Values RBC - redblcoellocoudnt HGB - hemoglobin HCT - hematocrit MCV - meancorpuscularvolume MCH MCHC - meancorpuscular mean corpuscular hemoglobin hemoglobin concentration RDW ARET - redcell distribution width - absolutereticulocyte count PLT - platelet count WBC - whiteblood cellcount ANEU ALYM - absolute absolute neutrophil (allforms) lymphocyte ~ AMON - absolute monocyte AEOS_- absolutecosinophil ABAS' - absolutebasophil ALUC - absolute largeunstained cell Summary of Coagulation Values PT - prothrombintime APTT - activatedpartial thromboplasttiimne DDuupoentw117u63s ~ - fgompany SenDioostnoticonztaineTSdCAC.BI 2H6-2-5D5a0y9:StRuedpyieantMeaedl-eDRoRsaetDsermal Toxicity --~ _-- TTAeBmLEeS DwDuepown-w1r17s63 EXPLANATORY NOTES (Continued) ABBREVIATIONS: (Continued) `Summary of Clinical Chemistry Values AST - aspartateaminotransferase ALT - alanineaminotransferase SDH -sorbitol dehydrogenase ALKP alkaline phosphatase BILI - totalbilirubin BUN - ureanitrogen CREA - creatinine CHOL - cholesterol TRIG - triglycerides GLUC - glucose TP - totalprotein ALB - albumin ~ GLOB - globulin ! CALC - calcium IPHS - inorganic phosphorous NA - sodium K - potassium CL - chloride PFLU - plasma fluoride `Summary of Urinalysis Values VOL - volume UOSM - urine osmolality PH. URO - tuhreobliolgianroigtehnmofthereciprocalofthe hydrogen ion concentration UFLU - urine fluoride UMTP - urineprotein --~ - Eompany Sanitized. Does not contain TSCA CBI E-- 2He6:2-5D5a0y9:StRuedpyeiantMead-lDeoRs-- aetsDermal ToxicityR-- RR --r DuPont 11763 -_ TTAABLBESS 0000000 NOTES: EXPLANATORY NOTES (Continued) Summary of Hematology Values Summary of Coagulation Values SummaryofClinical Chemistry Values Summary of Urinalysis Values `weWrheenpearnfionrdmieviddouanhlaolbfstehrveatrieocnorwdaesd rvaelcuoer.deFdoarsebxeaimnpglele,sisftbhialniraubcienrtwaaisn vraelpuoer,tecdalacsul<a0t.i1o,ns0.05 was used for any calculations performed with that bilirubin data. PN ~~ Company Sanitized. Dossnotcontain TSCA CBI ~ 3 2 css aos. oo BES rE a se glgiioraioraaianl| 8 8T BT 89 85 3% 3% gm of 2 i Foie 3a nt af ak aa es af oS) f agg= . il 2 252s i23 ~ z4 = &| 5x ::3: 3:23 3 4: See immadaraarnl| Zg SET T ST RT RT RN BE ER oe d ES Ecdl tT 8 3 i: i 5g82g 58% 25% 5a 2 5= or E BR a = 3 |i3 i E [3 FE I 3 8 Company Sanitized. Does not contain TSCA CBI ~8 Bumanngan 2 ~ g I 3 i:3 ~ 4 24 -- 2 bg 888383833 2a2r2g7 52 vY aX E ey aon nan 3 egod i: & ces. a2 B2 E2 2 8 8 8 8 8 3 8 FAaTf eRYags7 odSS egef 58.g8e LwdE gg = g 3 3 2 8 8 5. 22f FEE = FUE ASSEEEN 2 Fp fgg 2 5 =5 35 %H 8 93 8g885 82 54 3 88 2 8 : 38 3 aLdE i F3 i 5 = 2 oG g y9 Pf Bo:s i k! %Z ||: 2 HE FI CompanySaniized. DossnotcontainTaracay ~8 2 Bane os 3 $s 3 5 5 = i So. i.2EE El 2 a ogd gd go 8 gs 2 : : 8 $ 5S=s ss225 85 8= z$ -- 5 28 Hi 3 ggga oR o8 a xi } sB2223 :v: 5? z &E I {332 i ~2 TE=s8 g 3gs 38s 38s 38s 33s ! 2 53 8 > MO gh ge gd 4 sge Eol F 3= i7 z 3 55%332 8 ys |H3 ggesd 85 003% 2% 58s zt 5 88 g |, df3 |%o% 48 8 BE 3 & & !o Ii 23 Company Sanitized. Doesnot contain RCA CBI ee z A 5535 3 gg 88 32 33 88 uf 2 g33 3 1} 2 So oo oo es Se is : Sits 2cos8 oa 8 8 8 BE . 35 8% 98 sr es i 3i _ 3+ FE5 He 8S28E% EHg Ras EhHs zx 2 ES : # 82 fs o & = s 2 8 gg 8 : 5g%e .oBs EossE8gaSs SszS)| 3 2 z ER 1 i z3,4 33 i ~2 ig a _ g gy 0a % f3i8c4 o3s 07o%8 8d 8 8 3 E0 8 iz3 og | i3 & |1 [I ' 2 ee 'Bompany Sanitized.DoesnotcontainTSCACBL ~8 :f sig we io << gg iP-" :k mzo 27; Lz o. Pn z fLz Fg1 ~ Ea3RJ4 E ee :Z g e... : zg "I 5s&5 SL o isg ooe PmEoo e . g fd iF ii 55i3 Fps loi3 lH HiooH d Hfgf ogEgEf 4gi Ha I --~ gia3 uHH g7 h8 od S Eih 3g E 3i x$ -- CompanySanitized. Does notcontainTSCA CBI ~ 3 3 : sho 3 2 il 2 g z `3 i z +32 "2 - gt ji 5 ieHEN : HEE i z - 4 e FEN 1siY 3 5aq 52 HER Fg H% } ME : z Fg? Z Sled z 2. AF HE iif & i, Bi 34 fil ii !g . &d8 e 3931 o8 fa2 Jadeg =5E3534 H 8i53:fd3E3SE382:4 38 i1|5i1is} GampanySized. Doss not contin TSCA CB! 3 Fi on 8 4% 8 2. __ ii gr ad ave "e "3 if (if 2 ii -- 58 : EEE Z gsE ifos g a= LIF c Ebdids Z _L 1 S Ez ERE: I 3 Hi T E 7 ET 3 skid : fin 54d IE del ~ iid4 PB f3oa aod dEBT FF iTiET FeFOnd Fe BRTiieg `CompanySanitized,Doosnotcontain TSCA Cal H2.62D55a0y9:StRuedpyeiantMeadlDeosRaetDsermal Toxicty ~ TABLE 7 PERCENT SURVIVAL OF MALE RATS Dupont-11763 Group: 1 m Dosage (mgkg) 0 5 v vi 50 500 Days on Test 07 110000 110000 110000 110000 2114 110000 110000 110000 110000 ---- 0m--re ede RO Numbeart study start ~~ 10 10 Aliveon testday 27 10 10 10 10 10 10 Percent Survival = (Numberofrats alive/Numberofrats at isk) 100 Numberofrats at risk = Number at study start. _ There were no statistically significant decreases in survival -- `Gampany Sanized. 00%not containT sCACE! -= 12.52-5D5a0y9:StRuedpyeisntMedl-eDoRsaetsDermal Toxicity Dupone11763 a. TABLE 8 SUMMARY OF HEMATOLOGY VALUES FOR MALE RATS OGrmogukp1e GSromuepIe Group V 50 mg/kg Group VII 500 mg/kg RBCDA(xY102%8uL) 755 2.36 711 738 037(10) 041(10) 0.4209) 0349) HGBDA(gY/d2L8) 152 152 145 150 HCT (%) 0610) 05010) 030) 0.40) DAY 28 461.39010) 455 14(10) a2 250) 454 1.06) MeDvA@Y 28 613 620 63 61s MCH (pg) 14010) 2310) 130) 230) -- MCHDCAY(g2/8dL) 20016010) 20057010) 200759) 200330) DAY 28 3025710) 303.5410) 302390) 330.300) RDDWA(Y%2) 8 18 7 17 114 ARET (x10%L) 03010) 05(10) [Xo 036) PLTD(AxY102%8u0) 25638.24(10) 2356.40(10) 5220.600) 251310) DAY 28 12917404) 117005(6) 1139 670) 1095 108) WBCDA(Yx1208%uL) 1828 17.19 18.42 1484 ANEU (x10%L) 290(10) 370010) 52809) 1.930) DAY 28 20.3421(10) 20..4486(10) 0249590) 2015879) ALYDMAY(x218074L) 1481 1365 1507 177 --_ 27910) 331010) 42700) L40) TTT RT [Eompany S nlz ed. Dose re t contaainniTM sc Ac E---- M0 12D52-5yD5aS0y9u:SluRdyeypiaitMneMadi-elDeRoRseaetssDems Toxicity oDuwpontn1176s3 ~~ TABLE 8 (Continued) SUMMARY OF HEMATOLOGY VALUES FOR MALE RATS Group 0mglkg Group In Smgkg Group V SOmgks Group VII 500 mgke AMON (x10%u1) DAY 28 00.5123(10) 00241710) 043 02409) 0.40 009) AEODSA(Yx2180%4L) 021 025 013 0.17 ABAS (x10uL) 0.13(10) 0.1710) 0060) 0.129) DAY 28 000271010) 0010s410) 0.16 0.09) 017 0099) ALUDCAY(x2180uL) 021 019 018 01s 007010) 008(10) 01109) 006) Pp Dus amnged ss: SMteaanndarddevinon(Number of values included in cleltin) * Satistically significant diffrence rom control stp <0.05 byDunpec TabaneDutt st. ~ - Company Sanzed. Dossnotcontain TSCACB ZDH2y-82-S5D5ua0y9d:SytRueidpyenaiMnteMlda-elDeRoRseaetDsserma~l T~oricity --_ TABLE 9 DDuuPoentm. 1i1763s SUMMARY OF COAGULATION VALUES FOR MALE RATS Group I Omglkg Group IT 5 mghkg Group V 50 mg/kg Group VII 500 mg/kg PT (seconds) DAY 28 15.7 152 152 153 APTT (seconds) 0.5809) 0.6(10) 03(10) 0.7(10) DAY 28 200 188 189 18.4 150) 1.7010) 2.0010) 1.9(10) -------------- Dawamangedas: M`Setaanndard deviation (Number ofvalues included in calculation) "There were no statistically significant differences from control at p < 0.05. --~ mm _-- Company Saniized, Does not contain TSCA CE! Ti ZDH252y-5DS5a0wy9:SytRuiedpyMeianitMeeda-reDoaRsaestsDermal Toxicity --_ TABLE 10 oDuwponte117s63 SUMMARY OF CLINICAL CHEMISTRY VALUES FOR MALE RATS Group I 0mghkg Group IIT 5 mg/kg Group V 50 mg/kg Group VII 500 mg/kg AST (UL) DAY28 ALT (ULL) 114 18(10) 124 27(10) 116 18(10) 118 52(9) DAY 28 SDH (UL) 49 7(10) 53 1210) 48 11(10) 53 279) DAY28 ALKP (U/L) 14.6 3.5(10) 13.0 4.8(10) 11.1 6.6(10) 136 8.6(10) DAY 28 BILI (mg/dL) 193 33(10) 204 33(10) 170 37(10) 207 53(9) DAY 28 ~~ BUN (mg/dL) 0.10 0.03(10) 0.09 0.03(10) 0.07 0.03(10) 0.07 0.0309) DAY 28 `CREA (mg/dL) 15 2(10) 15 2(10) 14 1(10) 15 1(10) DAY 28 CHOL (mg/dL) 029 0.03(10) 033 0.05(10) 029 0.06(10) 028 0.05(10) DAY 28 TRIG (mg/dL) 56 5(10) 56 8(10) 48 10(10) 40% 14(10) DAY 28 `GLUC (mg/dL) DAY 28 TP (g/dL) 44 14010) 87 10(10) 49 15(10) 95 24(10) 39 10(10) 104@ 20(10) 26* 609) 98 15(10) DAY 28 ALB (g/dL) 6.4 0.3(10) 6.5 0.3(10) 63 0.410) 64 0.4(9) DAY 28 --_ 4.1 0.2(10) 42 0.1(10) 4.1 0.2(10) 43 0.29) TTT a anySantzed.Does not containToRee-- 2285:5D0a9y:StRuedpyeaitneMdl.DeosReasDermal Toicty Dupont 11763 ~ TABLE 10 (Continued) SUMMARY OF CLINICAL CHEMISTRY VALUES FOR MALE RATS Group Omgkg Group I Smgke Group V 50 mg Group VII 500 mg/kg. GLOB (g/dL) DAY 28 23 03(10) 23 02(10) 22 03(10) 22 0309) CADLACY(m2g8/dL) 1 11 109 108 IPHS (mg/dL) 05(10) 05(10) 03(10) 0.4010) DAY 28 9077010) 9104310) 10051010) 90.640) NAD(mAmYol2/8L) 1485 1484 1480 1488 K (mmol/L) 21(10) 20010) 17010) 26(10) -- DAY 28 640 028(10) 631 0.46(10) 663 059(10) 629 03409) CL (DmAmYol2/8L) 1004 1004 101.3 1015 2.1010) 18(10) 33(10) 3.0010) PFLDUA(Ypg2/8mL) 01 00 00 01 re01(1e 0) 00s 010) e 0e.s0(s1e0n) t 0.0e(10e) ls Daw amnged ss: MSteaanndard deviation (Numberofvalues included in calculation) @ SSttaitsisitciacallllyy ssiiggnniiffiiccaanntt diiffefrreenncceefroomm ccoonnttroollasttpp<< 00..0055 bbyyDDuunnnestteTsta.baneDuane st. ~ Sanitzad. Doss rotorin TSCACBI - ZD2F-8u2-5DS5au0y9bS:tyRuedipyneianMtMeaadle-DeRoRseaetssDeal Toricity 000000 DDiuPeontn.11763 ~ TABLE 11 SUMMARY OF URINALYSIS VALUES FOR MALE RATS Group Omghkg Group Il 5 mg/kg Group V 50 mgkg Group VII 500 mg/kg VOL (mL) DAY 28 91 5.710) 128 5.510) 67 10.1 2.910) 7.610) UOSM (mOsm) DAY 28 1161 704 1291 1235 pH 771010) 390(10) 699(10) 1099(10) DAY 28 70 03(10) 71 02(10) 69 03(10) 7.0 0.6(10) URO (EUAL) DAY 28 04 03 04 02 03(10) 03(10) 03010) 0.010) UFLDUA(Ykg2)8 95 133 2.0@ 1472@ --_ UMTP (mg/dL) 258(10) 41010) 3.910) 40.39) DAY 28 7 58(10) 36 32010) 62 35(10) 70 88(10) _--_-- Das arranged as: Mean Standard deviation (Numberofvalues included in calculation) @ satsically significant difeencefromcontol at p< 0.03 by Duns est ~ Soniizad. Doss na contin TScacel Tees ~i z : PR gd ac 4d &5 dS G6 de ae ig 3% o Zo iEiaigiaiae aia ou EE RR CRC EE 4 : 22 . zZz io z 22 ge aS As 83 4d dd dd a8 ad 3IE g Sg g ; Pog .2 gd i8 =&| Company SeniDtosisnzotecondta.lnTSCACB i 2 g] me cs ss cs co Ss Ss "eo ss ag a g gH me ce cs ce cs Ss Ss oc cs : a22 gE:i& 3: 3 zz 3 3 3 3 2 ne me es cs ce cs se cs cs Se g is Th bdo thoih LH `Company Sanilized. Does not contain TSCA CBI ~f zi 57 g gd @4 8 ar ds i i _ EE ss ozo: ozo: oz 4 f 2:2g 3 iE dog d ae 5s 5 35 35 5048 53 Codiosa 3 fF 3 H :2 z ) . 1i3 i&,: i4 jHfaEsErpbowrBaBhBBhG1 yf: HE BEB GE Hp: Eompany.Sanltized. Does not contain T=~A 81 Hi ~8 i 2 ei FiI 9HieIy | Son S2 enn I TS 2R5I 05Eo | gpg cnc B 1R % 135s 3= 4 (Aa BH i= i oo frErER 5ge=5c3ig1}8 ga" @aAagR ia 5f B dlpT . T [8% s 83 s F=a 3=3a si2E 3 Ce HOE HE ETE 2E z | F iiiFEF iiNif%gsy2 --~ aa B5O!00i} IjiEe . 52 ] gog !i i188 $ EigH g | li &gg= |i| ii] iH1 )feg: .; Zgg |i| fi og DoE B LBLCEH E4 D B4 OBEgiisade i ; i PoE | : gE pp BR su 33 iEe EI4E: 3 --_ EH EPPERfEE lE peEpfL i8e88Rig4 ecggBahFeo lflapeasfd i {|B gf 8 iE -- FE =3& `Company Saitzed.Doos notcontainTSA car ~8 iriiioan 3 2 TyoT. ---------------- ijdife%n j| s3r2E8 Re3s85 ie5z35 as3ei3e | lglss, [S238838282382 B[Bllo.8Bi e| 2s9 az2a7s3a8s3e2c3 z8e3 %i8 (t3 Cr io flr. B38=828:2=82 5 ii i i z | i j i 30 ZSi E iEH ~ g 2Sid; $E H14% e. it PF 82 8 | ! iiz g5 i| i HxHd io 5 Nooo di i Hob i ~8 ggJi : Hp P ; --F8 - 88E08#88 F 88 F88 8F8 :i`5Fe#8H3 ; PEE EEE la ] iE OF OE OE OB OEE EE FI IE f I7N F r v EPM F ig 2 &| CompanySanitized. Doss not contain TSCA CBI ~8 Hi Heli igagagegagage | igieh, 182828282823! Ir, Bi py 1 =2828382323i%: p iE i813, 1823823823822383 (5 gz ifpedeFREE 5 a2 ii : ifs ~ tlEo i H=op|, No ,sl 5 i Ek ~% ] iiiiiiE g2 l i| i5i g0a i a FEE E ag EEisl| i COE EOE OE OEE Hi HIEY Tgd 2 4st Ch oETpeEgpryefe --_-- 7C t F id oo panySanitzed-DO otoTOAOR ~ : ~ . { 3 ii, jEi 3 9 ag) = &| PR olEigf3f Beit is oT. flgpg {8282823238233 dvi igigh. {8383828283z3] Bla y 1E 828282P 328233; f syhi 2=Basr a8a8:o 80i0 n z ifTig gg if i2i3 EH E $iE d ii {23 gE | | S2 | i EL 28 | : 158 5 jg8 ' 28 i EH Fe i =i i i gS i| |i 4s Hc Pud g| g |i i {8 8 8 8 8 gii#e PE ELE ob bi i| lpEeEfgf2eglE EB.E5 58 Po, i SEgin grEeg ils |iPdF e E[ESerdiEei ZiEZefEeTdETeafaie iipast IE --_--m ee IE CapinySuits Doo no conan TSCACBI ~8 jae | Brgefafeagage iLifRI!3e598s8sI 3g35| BE se zg Bl Sn i 328282323:23538 gi iF 2 fEloYg, {i s2.2i3.3z2es3e8z8a8z8.23[25 fh" 2BoE5 | IE ifs Eg A{iE.i ~ 88 | | jin3n2 Eo =cz8 || !] 53 | ; sfiyef [|8" iz a } | 153 7| 2| i| iifs . Epo Z| POF FB OfB ogOB OoBp ogget g ; pF BE OE OE OE is I i L,oiddgdld PE opsstiif dal1i1ikh 5iz ~8 i{f 4 t P[EfTeEC feEF fTEeTff EcCF EiTciiOss0Ld2 22 EgmpanySenitized.Doesnot contain TSCA CBI ~z : ET iji8gF 127223" 3382s! Hi jgisk. jE2REAERIR AER Bln iEszeiszsizzisf go gly I%, ln Brrriacies 14} a2ziiE i g1E3 : g |igIE : 1LH82 _ EZ | i-- 132 88 | | iis 1 3 zg i ; 8 8 8 8 ih 8 &8 (#4 go ie EE 8 EE aE 4 BEEFE INE 3 i: _ i2 i fe ik iE 53k i g LE i fgegeieieiele ul ; LRE- FF a 5&F OF#& IiEi EompanySanitized. Does notcontainTSCACB ~8 : TTI Tir jf zERsagacn | J gig jc rEERE To lp ial og ii g2 eg= az=ai=s 1ig8 g H2s /o2 li EgBsas3sesg ggaaif:a s i[EE 885 iiiE | ~ Ex il 8 | i EA | 4F8E | ii ii : EF (8 ii: 3 i14d4 gZi| ii g| A 1i5cgt ) . Z| ] A TE oF FB OE Hg og iH f ii i, E4s8 E BE EZSoEg Eil &i3 PPPEEy ol (BlEei srfklego0F efiBacdal agoBdL ~ 33 -- ; ps FREE iE =3 Company Sanitized.Does notcontainTSCA CBE ~8 i 3 iHBT L(EERE 2 osm g lgigis|h i E5O OIEY spd i ig PEE 3 {AL teED 2 LR. 8 ao is g g5E 0j f E iF y i1 ig gi i ii3 fE e T| i5t ` ~ i5 g | | i{f5y i 1 3 :| i13 5z rm 2 28 2a | g| ga | o22ogg g| Za P 0| F ,FE Pi ood --_-- j| : i i{aEdg ] gs 5 iif :i| 84N i8yg:f 88y xF iiv5yg 8 [8 |iLoEO Noa8IB n a L a 18% bon EPE gRFiEaeEsNiEYEgMiiadsMEiigno iE g geek [I Bog i855 IE EE Eompany Sanitized. Does not contain TSCA CBI ~g 3 BT LET 2a 2. 2. 2 ig BE SF SR sR Pol g igleis|h i g3 oOBoIT giREe iy iE &J igi a g Ei R S53 3R9a So in 0 < } ; EIEE] ggo 1 F i ii i igs 89 | i | {58 : 5 PTT 123 3 | ! ~ gg | i iIgH 5 2 | isk v 28 i ide s SLgH i32 ~ 53 g| i RE g| | Is ) o2gs i| Ai{ gg i13i5d = | 0F Ein ggo| PfEeFos: fpiisd 8| " is EE: R: E} By o} Fg p{ i2 re geidg fem-- me iomert z i{i2f1 - ossnoteontsn TAA `aSme p ~ ; IBla 2-52 3a g igislsk | 3 EHE H gZ ioEdl7 eky |: J T: SsTe z R=CHi {42 if eo: or oi ag8ose: ii ii E : ij35z 23 - g 8 |J ;i i5fy : i$:e | iHH : 22a g ii i| i i[1t3523 g| | 5 % g g| Pore j g pik 1.7 z ai i i g I| f 34 = gggFoiPr:Eel EiiiH%: El 3 ] | 08 ge Es Eg iad iE 3 4 i ig; ~3 --_-- dE 88 =| . `Does notcontTSaCAiCnBI ~ 4g ] 5 :3 5 3i4 i3i] a9 =&| iTgi L(EREE | Bi fai igE, | 22%. 3 2a =5o.8 g2a4y j Ea 2 EigHiE 8 i3 2 2 FE ED loBB . | EgdE2%T3T8 E2N23E1 i FEoJ HS f de at A Hi H ii i igE: | i 3aE 2 | i ig Ea i go a5 i z: i ig ii g| : 5 g| 2| | iis Loe os op gE g| | EEE Ee gz i T FP F iid 8 | , |Z Z i i fs iv Zz P| F2g LiEs i 3 s0EZF ids : Aifgs EBERFgeFE F 2B5E2 Lilekd EompanySanitized.Doesnotcontain TSCA CBI ~g 3 24 BT LET eee 2a i1E g: IRBE || g "wees 35 g | iigigiE sks T | i Mie 3 IE] jem 3 EBT TE 2 i 1H ioE. | i 2 s 2% iy Pg 5 g 0 iF 83s8 i i5E i ElgE! | ~~ 8 i =3 i i15 i1588s iz 5 : {88 a : Co Bd 22 g| i 5g i ; FE ig zg i i| glgsiEt2 g 1342 z 2 ii gi i| | de2 4B5s 2 d5 52 8E1l2a8y LIER iE g i CE d x8 48m IFn SH i=3f gi| zE g o if la gies 2g IifNs z | iPog ir ogaf Pog oosf s2lpsd ~~ 857 fi 18 0B id ige = &| pocanatcanan T8CACBL g | | i ~ 3z (E5)LgEa 0T Eo vm 3aa | P 2 i2gigriario | li agEgifaEEd ]i gET feTm e EmmeT t Big 2 E i= i-- ife oi --__i%y yd i ; i5 EL ! 15% 13 Eg E&g i ~ | fn |: | EiiiMzs {5 ZcTgE || ii 1HE88 : 55 | i 2geg | :i Eh 58 [i1]k & 4 } ; Md IM | debe gi of Ear bc i ogg | J5 iPeEo gGoi.g4E3. 8y yPiid2 PE gimgds 9 ig: BoF pop EEG i1 ~8 LH ;PF oiisE,g of # gEe Eii fn 28 FE anystnd. pos alos TSERC ~8 lT B) Ep E c3r% F8T %r i : gee ETly S P3 hiB H r a E! ze ogee; PE o bi g 0 is BE iE BPo -- TT | - SSEs i| if EH itafs 05 A| 2 | is i| 2 gi2 ||| oo Fd am : gg i|| | 5 iE B85 is || a Boweoud of oAFk L2o2y uH18ia% iJi i fi 10% ii| gE E:B s2g 8EiE tdE1iis0nd isi 23 EH ~ 2584 e{1 oF i1EfE: fEELiELIE i E i EB i iIg ] s Ek Company`Sanitized.Doesnot contain TSCA CEI ~ 3 5 [ETI E PE OIREE | <2 i 2 pp E3 oEsT yfH g f m T i Shaant tSTo le i 0 0ig ii g SE g0 ifs ~ | g8gi|| ii EiH: 4{5% 3 =3 38 | i : : 1 : I] egg BEEfsRs if NE g ;i| RpgsEi3gEi2g Hddi Hog POMEL HWz ooo5:<gio0i r. PlIEga BgonEtEaand gue ig in E i182 33 ~ ii1 R | i EHE 0I.N ..SiA. 8 LEENST{E58 =& Company Sanitized.DoesnotcontainTSCA CBI ee --~ :;B Tl z 2 I ii k23 iEE =& joa Be Ec LT ooo ELLE --i 2 [BiaisEs iogE ly cr FEES 2 3: 2 =< ii i l ij i= a Jufd Eo0 i} ; 22 iE 8Ina Fo | 3isi ii11i3 gEg | i z2g: | | tih 3 ] i ggE || i; E iii ibis : Ero ] ig 8 Pon i is ig E i 2 g 0g| E8, 8 ilee B i i ik Fi PoE Eas ged i F PfR if E ER E ig i `CmpanySanitized. Does'notcontain TRCA CBI ~ 23 [ BgEET aEa TTn] 0 yi! 2zg ii gigisks | i 30RD aE iH ZOE irl Z (3 fk | 2 Come i sly g0 2 :8 | iE i 5g || ii ~ l2e3g% | || z= i 28 i 18 5 ijgi, EiE]t i113 3 158 : iig ig | og : i ior 2g 1| iPfE 8 805iM8 Si PE 2 i 5 is g| [i B02 0 is : TE REE z i f 3 F 2 i: 2g8 |i| [Eo Bd sE & ial bPfg olBEaEEEi E En ID ,gs (|l:o835F pgfiligeevqiEBplRa.cegd iEiHss i"2 3 ~~ i |i | fF BEeEf E 5ia8t i [fz Hi -- iF =| Company Sanitized. Doesnotcontain TSCA CBI ---- ~8 23 ~ &22 I 333 i3 ~ 5 8 g Bl E 1% E,5am 3FTF ae Eaord g lzlgis | : i go ETT, } si: g deb ce Ele EEE i _ g 8> 0i E ii F i E5igpt 8 go | { i ise 2: gz | z mm ; iizne g8 |i 5 |ii g 188 r|e a5 | =gg2 | i ; Ce EH H ] I gf &| iFogF gi i IN se ; |J |8 iRIgN gE 3 E : Eig IM gq 1448 ga g | go iiIfeE 2B4 .Eg5ERfgf sg8: 58 PE oEEEE gt E EM FEiEH g : } g PF E}| ! E5Tfe283% E e% Bi E5% Ee fi nif iT Pod lP5e4geT g2 elif -- `Company Sanitized,Doesnotcontain TSCA CBI ~8 i gpgig serene 8ig]i (1gB2EuE | ggg% 83g% 8253 53g34 : Ee g2 ligllgisEs | i 2 {BLE 13 Te 5 (8 iw. 27 2 = iz El i iiF | iijbatg] =o | i 123 C5 N HiE ~ 22 || | =$5d i| 8fge z5 ;:i 17 | 5i5187 PB 1ii%s5 3 12 a | Pi oe oro giil 2 I : ; [I & EEE iF Ea 1 &g | riggd BEEEz EtiEi H3 og eE, oF fF} CF E rd py gocf| o2sii o11 niE preps fe fei ~l$Hy2E f|o PPEeFE FoF FB08 CIE EH `CompanySanizsd. DossnotcontTSaCAlCnEL ~8 i 8f jg7jLaEe}1 sa Rr e 2RaA 3RRs| EET 3 EE i:g Rigel 0 dp go & lg ig i 5 8 1 HE 8g | ii gre 2 it IF FT FT TT iE i 125 PigH= [I $5 28 24 i g| g a. ii EH ide Fr | ii | ia (TE I | :Blogg| ioe oil Pod L,d elk El IEhk o2 i0PooffF iPE EEE e aEEC sg Be P8aEBdE ~ &3 fz: FC in 8 Company Sanitized. Does not contain TSCA CBI ~~ 8 a 32 i ijgeEdS ps"52 3=n" 3 3=n 2 | gP igigio sks | ly| gE i ~ 2le8r iLf ok zFg AigI LLf C gig zo ie ga i1 i iE i ~gg i| i i 52 5:2 33s| 128 25 1E8N% 1i8z8g e x2= 6= i i g| Sg i ii ii l1i8g8 i fad i i: |i 1| Pore iH Z| i gi g3l00Fgg ii 3 } ~ H$31E i I [8 oF gE Ei F. isi(8 BEgEFi 8B 4 8 0F0EiSe i ie ge Ee ifs pP=EF ER F OE iig 24 ' 5 ized.Doesnotcontain TSCA CBl ~8 i STE T 22 za : fomele Ee io g aigNigLzk || I 3 1%] zg 0 lr juo3b8 |i w 8% &, = ii:s : Pi E-- ES E sd f| || REE i1g83 iH _ :gE o| ioLme} i1EH3H% g gg gio i! ii{g5 : | | ie it i2Lg | i iifgy . i . i 3H1jo2E ~ i5s23 zo | I | g 8 ju Sk ius z| zg | jPg 8 a8 2 143 P8 oREELI i g ig Poa E g Fp Bis i 1% 8 |iPofofPoijiEffa;fegfo ggeiaf iidh iia i 13d f} emme- ime --8Fi iidE {Eampany Sanhized. Doesnot contain TSCACBI ~ ~ 3 i B igi EEeT FF zEsR Ig igigiake | 5 g F E o EE geli: Ti CH RE i S an So im Hiei 8 22 ig, eE00f-- ] 1D9u3d : i if if 8 | 8 | 1g =3 | } } {58 g Ei iy zg82 i|| |:i ii1g5fdy . ~ gg i | iii zF=I 2g ii i g; s iiif:is %5: i2q i5i z| i gy ity o2g |i iii asg 3a g T11u48s34 | i IE EE ZgZz || iP PEg EHER egil nBfiilgH 8 :| , ;| ELEEER OD % iis 002 LPFE 1igE EgeEk Egdiifn) ]PPE f 0d E iiiE 8i:3 Company Sanitized. Doesnot contain TSTA CBI g AR ETH, ~ igE i iBgE LE i E 1 s2a7. g iglgisks | | 2 deity L gE igi amyEiifi} z dali 2 5g in g | i ei i =< i i i zo | i 123 i13 2 ii 8 ig i P1E5D% aS : 5 2 SE a if ] i| n8e8 ~ | gg | ih Tz5 | i: ii1g58 2 | {sf 3 8g | | j1i8g i i gE gi Ly pik 3I gZZoz i E iE LgSE E3i% a24o Ei,EF IE lr Bil qin ~ ia:2i | FSS PEF i|g =& Company Sanilized. Doesnotcontain TSCA CBI ~ 3 WL 21: | HEBEL ER Ei 2 igigisks | i 3 ER 8oBi IT e RM iifi E g (E A oT R. L FEiE gg c im gEii I2i.]f8 ag& S2|i |iiF F : i5i8 gg i| | i3g x8%= |i PifEsE 28 i 1 S ag f og I Zogz 3i 2 z 3iz ~ 4 a9 z& | i Pad | ii 8 4188 i0 PiPEE oBopEHsEE{Ta7 | tPwrosEkaHra fien FC Eg ih i:! O i[13E5Bg gfid i19g3 ` --'E Company sanitized. Doesnotcontain TSCA CBI 2H-82-5D5a0y9S:tRuedpyeiantMeadl-DeoRsaetsDermal Toxicity DuPont-11763 FIGURES --~ Company Sanitized. Does not contain 7" CBI a 1252-5D5a0y9S:oRd en MplDeoResaeDssetlToexicdity -- FIGURE 1 MEAN BODY WEIGHTS OF MALE RATS o-- DuPont1763 0 n | i2i Ioo osmarme| 7i | 5acsshoommaeinss 3 | LI ~~ 20|3 7 mw ww oa 1 ow = Dsante --_ -- `Company Sanitized. Does nat contaln T&AA AR: F2-82-5D5a0y9:StRuedpyeiantMeda-lDeoRsaetDsermal Toxicity --_ DuPont. 11763 APPENDICES Company Sanitized. Doss not contain TSCA CB = 2255a5y09StRyesniidlDeosRaetsDermal Toxicity Duron 11763 ~ APPENDIX A Individual Body Weights ~ _-- J--------ontaln SCACB! ~3 3 3 % LoommEmn gro a BEER gf 3.2 fishatie gf oon : 13d Ef a So | 578 EE. mmm RASARRRARR zmmmmeim FHSg FE5 ~ 1 as BH iffo. 2 soamsmagosoaiiaes gesesess HEEEaasar 8333333888 ; 4 fe z LH ; 3 AnARaARmERiARnS ggagzsmans BEhBEREREE `Company Sanilized. Doos not onlin TSA CBI ~8 3 2 25 33dsasenis if La ERE FL fe GEE if 2 ie ~ 45.7 gamnvdesgzeivdnnsdes % 11, mom i 3 RRESHANARR I.y iEaRsRdReRRnAiRdEsR z3 ol3 S.; Hoi grigsdrsis HL zg 83833833832 2 888%8sLLLE Company Sanited. Dogs ratconia TORE! ~2 3 Lo mmm Lp oo mo Enmm f pra7 2R3LASRRER pif $i. somone HH RRRAAERRRE 2i 1 iZo;y $RgEtRERdReEsRiRgEsR BB iE iLaooeamemmam 39] ~~ ZZ 2 : BgaasRanas 33E3BEREES Leeanensn = 4 B3a3zRanes 33E3BEILES EompanySanitzed.Does otcontain TSCACBI ~8 , ananacaase i.0 ggsadsdids goo" 5 issisiis He BE 3: mmm ii ARRLIALREN Lo mba FE 1fE.l grzzdsiiss TE. acoaesaes 3Fg#o7 gizzssaesmeeds fo ommmun z 3 vz RERERRREAR 21 }2 o:f msfoERmEEuERmis Ha Ts3i n2 g PneaaEnaEcEneEe Bf ~ ms oi . gsazasesas Lh 83 EBEEEESES GooEER ; aGEEaEgEaEzEaEsEaEEz Gompany Sanitized. Doesnot contain TSCA CBI H2-82-5D5a0y9:StRuedpyeianteMda:lDeoRsaetsDermal Toxicity -- DuPont-11763 --~ APPENDIX B Individual Food Consumption CompanySanitized. Doesnot conta veracel -- a 2F-82.5D5a0y9:StRuedpyeianteMda-lDeoRsaetDsermal Toxicity --~ Individual Food Consumption Fo/oaDondany/Cdo7anys'. wale, I 0 masks sesseenrriiieeessr 222330.0242 sessrenireeisso 22256000'1s ss6e7en1i7m3 222060207 nna 203 gF/oaDondaayC/odenasy. 32ai52l.'s5s 222621s1 2220'3s61 0s gF/oebondanyC/aadinasy. 222310631.0 2 2283 22 2i604s Fgo/DoadanayC/odanasy. 22m65.'s5s 2221'''sss 22258''1ss 07 Hale, 311 5 marke sSenenrnmrs 221321303.06 222666.0s 2210.339 2208.'24s ssseeerrniisnnoee 2223600's0s 222606'43s 222660''1ss al26'0ss0 ~~ eseerriiee 227'63.5 2267'7s 226'2 2 z's Geeenreesd 220050 223s1 w2303iz 22000s wale, V 50 mg/kg aessnoeimneesrse 222256.0279 222064.s72 22260018 22258'.7s5 ss86on7n1eg5ss0 2a26s6sss 222603ss 2236'6s1 2229'6.s14 ssse66n1199s13 222'03s2 2201'%s 236'4s 022960032s S615 26s Fg sls 24 Hale, Iz 500 ma/kg sepg6n7id1o5s6 222636'.3s8 2220680130 222002a9 222'6.s20 eesee7rr2ig0ses 232300433 22073'5s 220'7sls 222'9's2s as6G76e77222000231 afor1ii 2a20s22s 2 22'0ss 2 2i8l'os cer208 3 #3 ls 23 DuPont-11763 CompanySanhized.Doesnotcontain TSCA CS! = H2-82D5a5y09S:uRdeypeiantMedl-eDoRsaetsDermal Toxickty -- DuPont-11763 ~~ . APPENDIX C Individual Clinical Observations and Mortality Records _-- Company Sanitized.Dossnot contain TSCA CBI Te eee Z F2-62-5D5a0yD 9:SRtuedpyea iantMeadlDy eosRaetsDS erm~al ~Tu oxicitd y yinMaleRDDue uPonmte 11763 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY RECORDS ------------EXEPXPI LANAATONRYANOTTESORYNOTES CClliinniiccaall oobbsseerrvvaattiioonnss rreepcoorrtdeeddipnostthi-sdoaspipnegndariexwneorteinrcelcuodredd.ed during body weight collection. -- --_ _--_-- Eompany Saitized. Doesnol contain TSCA CBI Ee ~g 3 2 2 3 Bes td [I PEieiia.snianitaiitoatatitas i 3 2 2 a8 sz a8: ~ 4 444 i4 444 a H & g3% = eas Tess LE fas & 2s Tess 7 gf 8 3 fy 533 333 $53 fy gg83T frig EEE Eodviagy jie figs iii fain IEERE frigid . Po2pbrigeeiiang tinn&bg2ing$, 5 Pllppisidiigiiitgiieiigy i Phieriidibiiniiatiiie Pi| Pfireosddjdiirisdgliededsigiiiaodeilftiicdisisisllei a ~ga3 Cic :. :. ". CompanySanitized.Dossnot containTSACBI ~t Fish 2 pF (T5r3: i fy: hh a hd, sb oab gr ud Yiic:i iis:i $1i8i 1 EE diy Bsr ig: Big Pofipl dig frrnofial din, 8Pil 2 hei2di dilz iii, 2 g2 " El pbiReritiaiiieritioaiiig Pf|g dffgrediiisleededicleedeairiciisisiiiiiliaislilys 33 i: 2 g 8 7 =3 3 2 5. - . = Eompany sanitized. Does not contain TSCA CBI ~2 Pix fool rp &cd ss 2i ek -~ i[I oc AE fo i | i f ag) = &| Poi sais ER LdLlr: if iE x &= s Company Sanltized. Doesnot contain TSCA CBI ~8 :.35% Edd o8iId8i2sRoRaST8sYdgR3=S3R3I80Z3A3R508 gE 3(:83 (3isd: pPs4f8 g(i8fd giid3 ; 3 fig fi: fy: fry fag EEE EE EEO EER EE S5| I& z i EE 5 ~ 3 2 sPdRiiipiirEiiiiiiiiisiiiaeiaiiireiiiiesi)giii dEididgsdgiiiFiEsYidEdEgErYaSiEdEeRsEdlin}s dirsidsssiiiissiifissilssii 518: 2g 58 8 5g g2 2g 8 2 i i i= = E 8 8 = = = Company Sarized. DoesnotcontainTSCA ci ~ Zz g i z i z pidr iinihr ih ine i2 dJ otpsi:l g1sh: tEeDr liHsD ji : oBsr Fig dry fig Pi: P5oPooid4ii3iEi3rg fZgii3itr3i fdfiiiiridnieJfisIiEsE HZdEiisEd, PoeiEg irr irri, irr tnd, El EdErugdiigiiiyidiigdiigg ifol dIiSEsErRdEiRlEiRiEiRsEsRiRiElEiReRsEiRiRsEcRiEi zg g8 iF ~ E 89 ci5. 2 8 .g .E 2 8 .# .8 CompanySanitzed.Doesriot containTSCA car ~8 105s it i ogar iia piiiSee.eiiloatisisiialite : | st 1 $f gd gd i fi Ey: izzy By Piling iiinigi, 1 fie fiiy jiiiy HEE] Fosiitog 113, sid 133 , loshrrniiiniiihniti 1 frdddracadigesidiz ell: i diesediiisediisssiidesi 5 iF ~ 3 5 22 5 = 3 8 2 > > > = = = Company Sanitized.Dossnotcontain TSCA CBI ~ 3 2 i ~ |I g if iisd 1ie3 H`e1 1g ir: fis fis 1s Bry fi: Bg Pot ji eee fin EERE iia Pia i341 Porbi $i i838i5ir3r3i83t3a:3n8t38i34i4d35,3 5 diitiriide pian BSl| oiojiidiiEifgEiiiiiiieaniniiitinesigiiiildingy $3 IEREEERENENENEEEREENEEN] 5 i% if i. 88 5 % 2 3 . . . - Companysanitized.Does notcontain TSCAC81 ~ igz ain in shaisiesiitale i ; 5k& 3 gs 3% ) - |ov3i5i3sf% gd4 111 PDifdri:. 1f1idg PPoaigsiioeisrlEgieegiigiidoEnie.ii?die AE fdiS iiiiEiRiEiNiSg T; ERRPEgLdEdEfEsRgIidEaRgEe ~ i22 i . 23 = ) : CompanySatan.Doss etconn TSCA CE! ~ i l8g2 si:Eoiu2i i4: r . fy 2 iid fii IPoolfsry: 2d3isg P; aBtEhF 1p113i33d; Pile ciii 33 dd i313 Tfiyg: 2f3y3: Fiiigi g14i4Pfi,p Jitiii,se; f1iifie3s itil titi in, S|ofibircpgentibeliintadiing I 3 df8esdsdcieidrisidileiasdedsiiisdiiedsiibieiasisiis jE 8 g ~ iJ i?:. . 8 ga 5 = = = = = CompanySanitized. Doesnot containTSCACBI ~8 i PEiisiaiitaed ireciin.iitg, g [g:I df E d0oEaiETn $gd1 4$d4 ~ Eivid: vii:f oyi4i%: 1ii:f yiff 3 S3 d33s83s8 isd8 fIEpErE $P3p3p d$6y7s8 i ji3 fr3godp5a8i4hoii5logi8i8d3l P8ogith anda iii, 2 gE 2 2 FE] FE] $8 i i S3ISERERIREEaERdEEiEEEE RREiEiRElREEEpEiTttfeli: i$i8;: i diesidiesiiessiiisaiIiElEoRsEsEiRiE 3 is 35 5 i ii 5 g Company Sanitized. Doesnotcontain TSCA CBI H2-82-5D5a0y9S:tRudeypeiantMeeadl-DeoeRsaetsDermal Toxicity --_ wDuaPomnti-1i17e63 --~ APPENDIX D Individual Clinical Observations -- Post-Dosing. Company Senitized. Does not contain TSCA CBI Tite H2-82-5D5a0y9:StRuedpyeiantMeadl-eDoRsaetsDermal Toxicity wDuPoontw1176s3 INDIVIDUAL CLINICAL OBSERVATIONS - POST DOSING -_ CEUXPLAANNAATTOORRYVNNOOTTEESS Csluibnsitcaanlceo.bsCelrivnaitciaolnsobrseeprovratteidonisn trheicsoarpdepdendduirxinwgerbeodryecwoeridgehdtdcaoilllyeacfttieornraermeonvoatloinfcltuhdeedt.est --~ --- Company Sanitized. Doesnolcontain TSCA CBI ~ i 2 i 83%: 0% 8 J 3RL 8 yaaa Rie dig 0A fRElE g ~i 5 $3 5 i% i 1 i 1 i 3 i 3 i2 2 i ' :2 2 z 7z z [EI i i i i g2 i EEN EEN fof Ste fre ds 5 11: 2 i 53 Efi3s i Figg : Paid 88F 5ig3 5: 3igg 233: 3: oss 2i Po: Sod opel ogi gd 1 Lg i 32% 22: 3 2 WOM THT HD ig 4 FE 3 3g 3 3 2 ~ $L5I fe 23 5= " .n . = = = = = `Company Sanilized, Doss not contain TSCA CBI ~~ FCs liz. Gdax I 3Eg 0d 5 J843R g sr 1 i g --: . i 3 3 3 : 2FE2 zz 7i zEH [ P|irogi rpi go 1 2 ie fie od B| (j2 df #4) 21:2) e ic i gf 8 i fie ol : fal i i: 8 g E i | 8 8 2 g 33 --~ 3 &w - " " 2 5x = = = CompanySantzed.DoesnotcontainTSCACBI ~ 3 3 883 0 0 he sah HE so B g HER AGE g ~ ; . : 1od 3i 3i 23 2 2i : iig2 2: Fi, i 23i i2i 2: 3: 1i Pilg rg fo: fos gor pg Fe ji; P34 $F 0: fos fog Pig foi Glog 5 f [EE Eo E ph ifd if: b :d ii dI 8 R 3 E 3&EE1E EFEyE iii 1 EE%E Bf i: ~ 2%3 i2 x 5 i 3 i= = = = E8 = = Company SanDioestnoticontzaineTSdCAC.31 ~8 H : 4 -: . E ld Pod yf 2 zi g iff F1Ig 3 Po2 g i PE iri: i i 5 i PEE 4 1 ssEi id o1zo: i 8 4% dify 31% 1% sl be dal 1s = ix = = (Company Sanitized.Doesnotcontain TSCA CBI ~& 3 B88 0% 08 Nan 03 dhs desE 0d. dE Be : g --_ i 2 : ol 3 13 1 : FE | if 3 2 i & $ & PEEL fof f5 loglPoloibgtl:y i dd sdb i IE Eg ry af oe ffs qf d Ppidlgi d fy: Pi o bPii oi} 15] is 3 & 8 3 BH i= x = = = Company Sanitized. Doesnol contain TSA nAT ~8 5z B20 003 0nd 0 a0.8 28h 5d BE g 2 PN : ; ig ioiy 3:Ii3 1i ii : par irl ber fos 5 $dP,ra0i0 h 3boririiis:l 4fod: E fg i fg i iq55%fF 32 LE) = = = = CompanySuited. oss notconanTSCA: ~ i33 FRozhe dH dL EDGE TAGE A ~i Sol 3 3 1 1 3 3 ' [I i a. Ff ;1 Tp Pid pr bs 1 Pg onig fs fay 2 i sf B2 p orp o5 rp i2 fsi ts 5 Eg fy be Fog Fog Bo Bod 3 dy ib oP op ob foros 25 3 8 3 8 8 2 23 3. ~ 25 E . g . . & " . 82 $= - - = - CompanySanitized.Does notcontain TSCACBI ~8 2 PF0e8r4ildd Sas 3h0d od BuARhH --_ : i i 11 go 3 3 i ' i& i & & 3 3 P Ero H 2 ofgy 2 0 2% 2fF 2% 2 i 2 di4 f53 i i2 F{i E2 Posi: fs fo 5 3 i$i4 B2S4F; Fg 48 D3E% 0%3g3 17 14 de di 8: fF 3 ~fSf25oefg.F8 LL 3g 2 x 2 Bl oi. . . LompanySanitized. Doss not contain vara mas -- 2E8Ho-D2a5u5y0S9S:teRuedpbyeisnbteMdel-eDtoRsessDermal Tosicity --_ oDuwponte1176s3 --_ APPENDIX E Individual Edema and Erythema Scores -- - Company SanDioslnoticonztaienTSdCAG,BI ---------- H2.82D5a50y9S:tRuedpyeiantMeda-lDeoRsaetsDermal Toricity DuPont. 11763 --~ INDIVIDUAL EDEMA AND ERYTHEMA SCORES EXPLANATORY NOTES DRAIZE* SCALE FOR SCORING SKIN IRRITATION --E_--valuationof Skin Reactions Score Erythema and eschar formation: VWelrly-dsElfigihNteedrCythYemaC(barc ely PErceptibler ) n ss: n. 1 2 (Slight) (Mild) Sp evere erythema (beet redness) to slight escT har formation (injuries in depth) ........ 4 (Severe)0) Edema formation: VNeOrCy sCliMgh.t edema (barely PErcepible)........nvvvenrsnnsnsnsns 1 (Sight) Slight edema (edgesofarea well defined by definite FaiSIng)........mrne 2 (Mild) rr SMeovdeerreateedeemdaem(arai(rsaeidsmedoraepptrhoaxnim1a.t0emlym1.e0xtMeMnd)i.n.gb.e.y.on.dvtmhvesasriasosfiesxpnosssusree)s. 3 (Moderate) 4 (Severe) e --e ------------------------------eeeeet & DEdriatiozrei,alJ.CHo,mm"iDtertmeaolfTtohxeicAistsyo."ciAaptpornaoisfaFlooofdthaenSdafDertuygoOfffCihceimaliscoafltshienFUonoidtesd,SDtrautges, nAudstCions,mTeetxiacss,.1T95h9e, Pp. 4659. --_ BompanySanitized. Does not contain TSCA CEI ios ~ & i: i: i: : i: ~ |i s ,. coceccsese cosscccoce ocscccoccs : ii: soscamwose esssscanes elsnsveses ii i: i fd 34 iz gf iif : : ~ 83 ; ssssseerer | senersasn ; mussmsem Company:Sanitized. Does not contain TSCA CBI ~t 35 5 sccessscce i: gp; Tet 8gp& i: ,. ceeseenses il; I eecosseoes ~ | 5h ` f,, ooomee % "id sroraveces ii: i: gl ogy i hE, 1H3oli0 Bocecccccce CompanySenitized. Doesnotcontain TSC4 nf ~8 3 4 ik i: ii LE | ii ~ | ii: IF w Bf; ccccoccooe cococccoce cococcccoe $ } i: ioi Woo 33 Ho far : : ~ 2% 4g esecscesse csccscesce scccscescn 7 sssgssRiE: CIRSEEsNsE | S35BIRANER Bomansnc.osotsmn 201 3 5 3 seeessusss i: i: i: i: 3 i 5 cccccssscs "dz ~ | ii: oecccccece : ig:5 cocooceeee ' il; i: got 5 a EH LS =8 8888L8eseE pomp: Sanized.Doesno contain TSCA CEL ~t 2 i g ~g z i i [5 eesessesse sescsense sssssesees LI 5 1 ceesseesee essesseess cessecsse & LI iil 1: Hob : : 53 9 -- i2s8 3g coeesesces 2 coconacncn 2 econcncces " gesseessoe peszagsgsy T $858I8888% SB3B3E3SEEBEEE3REEEE E3BSBREEERIEREBREEEET S3E3D3RBREEaE8RsEER ompeny Sanitzed. Dossnotcontain TSCA OF : 2 3i iE 1 5 RB {:i LN i5 b:g sesecssses 2 243 i24 fF $8% PL EB3aEsEa33nRaansaE Sanized. Does ntcontain TSCACE! Company i 1 secsssesss i. BE eoccecccces eccccecec0 eccooocccs 1;f . IE Bg, i: eccecccscos -ococousesse eccecesces eccccococs cesseenses eccccococs occecoccos sessscesss eccococces --_ g 54 & i f: eocceccsces eccecesccs ecccccescos fia . i- FE ececcccccs eccscocccs ecceconcceo z EH IEEE i 32 . g cococccsee L cocosccsse coccccosss Hogi ! } HE 3 TERINnE sromeneen wmMmEaney CompanySenitizod.DossnotcontainTSCA ~ ~8 5 2 coccccesce iz fiai ececcoccos Jo ooveeenes Pi go cocecoocee i: Pg. eeeeeeeeee gLli.f emeeeeeeee ~ 8 pi polsPg. eeccecoces 8 Bi fo eoeccosces i: El if. i i : : eococcccoe = | 8888888232 = amp Sez 000470 stainTSCACE ~ tf fu coccessees occccccccs ccoceccece pi ! : cocccocoos sssccccess soccccccce I: cocccccoss ssoccccoss esccccscce Hi{2 Efz cecccescos cooeeococe escoscoseo ccccccccce coocssssoe coceccccne ~~ gid 2 i f 3 eeseessces cossscsess cesenescoce I~ gee fe cccocc0000 3 cossccccce sssssccccs 13 ccocco0ese sscccccccs eeaccscane f i : coccoosess coccccosse escccmmann 3 jz 53 Ril : : 8 3333333883 2333833338 3BEERGEESE `CompanySanitized.Doesnotconlain TSCA ~f fz fg ccocesccoe ii fa cococccsoe ti pi ii2 "ri cococccccce ~ |i: s i 3 cococccccoe T i3 f2 iz eococcocse ios, 1 fo ococoscceocs EE 3 Fococcocace CompanySanliized.DossnotcontainTSCACBI ~ 3f , gi - i:3 4#: ii i5 cccccccooe coocccocoe ocococccoccoss i: ib i fa occcccoccee cccecsseee ecssescess HFHoefsp cennennenn ccnsnenes oenoonees Hoi : : ~~ 82 23 ggsgsgsans : gEREREsEay : gssgazanny 3 33E3E3333% 33833B338%F 7 SE3BEBEEsE Company Sanitized. Does not contain TSCA CBI ~t 3 2 i ~ &|: : i T i fr ceeceseces i: 5 [Ee LI i Jr eosoeccoss EHI + Horak CompanySaniized.DossnotcontainTSCA Cai Z2Ho:8D2-5Dw5a0yy9S:SutRuddyyeiinnMMapllDeoeesRReaatDsaesrmtalToexicdity --_ 00000000 DDuuPwonit 11763 -- APPENDIX F Individual Blood Fluorine Levels Company Sanitized. Does not contain TacA Ry -_-- Ties ZD228u5-5yD0as9y:uStlRueydpyiieanMtMeudle.eDRoRsaeassDermalToxicity --_ 00000000 BLOOD FLUORINE LEVELS TEST DAY 27 Animal Number Grow Dosage (mgkgds) Fluorine (pm) 6666771i6656 11 667167 1 667168 1 667169 I 00 015.57 0 <0.5 0 0.58 0 <0.5 667175 m 667176 m 667177 m 667178 m 667179 m 5 <0.5 5 <0.5 5 <0.5 5 <0.5 5 <0.5 ~~ 667185 v 667186 v 667187 v 667188 v 667189 v 50 1.83 50 116 50 1.67 50 1.14 50 1.55 667195 vi 667196 vi 667197 vi 667198 vi 667199 vi 500 500 500 500 500 19.35 7.15 6.52 5.07 8.49 a <03 isbelowthe limitofquantification oDuwponee1176s3 - Gompany Sanitized. Does not contain TSCA CBI ws H2-82D5a0y9:StRuedpyeiantMead-lDeoRsaetsDermal Toxicity DuPont-11763 APPENDIX G Individual Animal Clinical Pathology Data Eompany Sanilized. Doesnot contain TSCA cB _-- ri 2H6--2D5a5y09S:tRuedpyienstMeadl-eDoRsaetsDermal Toxicity ~~ DuPont11763 ---- TIONDWIDVIUDAUALLAANNIIMMAALLCCLLIINNIICCAALLPPAATTHHOOLLOOGGYYDDAATTAA EXPLANATORY NOTES fre p--Aomra asdaeqmueatec.lottes MEHEBNOnNLTC GohoattctetCnaaekkeeendn odurerotto hpeemroftoyrmaetds Q[OEX r eSqauraypnlceitgyconneodtirtissounitiofcieonbt tfoerstitnagsting UDTI uYneabhleatno determine matv`iBdcuaElCR=emssrtoaoarlpobigleyoocvgoanlcdueieltsli:onsount AwGB e Re emoglt obin MFRHGoCHW CromeemdaanncocCloolrrppuuassiccsuuvlleaiesrrorhhieeommnsoggwilioodbbtiihnn concentration --~ AoTRGET RpGlbauEcoeibsotte rcooutnitculocmyeee comt AEG thaotute neutrophil all forss Am Shaotute yrohotyce 2Rav0oe5n 1 aaSbbhmeuooolliuuutcteee bSsaoassrcigonenaipulhnisltained call Se 1 pect observations ImaioRvwiSeuCR=edoaBnrlioesooadcyctoolsltsMorphology values: CPiOHoLEY AN oapFctoyahlpniyecncchohhocretyooycmrreaaassssiiaa TWIGS CDCreRoorwgweoleti-svcoelillys body = 2 not heerved or not examined: seo whole blood sample condition IndiviodumSntCWhitNSemoirBdmlaaoeodwhCiatlel / Platelet blood cells Norshology Values: TOSVoRo VDToaoncuiutaeclmbaaotsaeetdcecosypntiotpslasm RSBe0C1D pGSileaaontotenliepllriactcelcuerteospieeemstimate B" D Snoit nGhdseptveecd aonf sot examined; soe whole blood sample condition ~~ _-- LompanySanitized. DossnotcontainTSCAcar Ti $T ySayp mle ---- --~ Duron 11763 --CLINIIINNDDIICVVIIDDAUUAALLLAANNIIPMMAAALL CLTINIHCALOPATLHOLOOGYGDAYTADATA sme, comes EXPLAN NOTAEST(CO ontR inuY ed) nttf [ e Ci hcot i o miassimoe y navis,on tiEiRCinE tos cr rane ann J g[S ErEoRESm ES aeadten eo din E gE=onoBalHoomes ren, ~ g= BEs yC ph iiBEaeeE venerne f5EHaErECC aBpimmm Ielmbeenle see otrr Tthrhe iSeEnEeR a TE cen CEE BT EIT erent of the reer som common o= | g EEemm, [ L oBCC SER wEloI Th, se BR ein eee Eompany SanitEizEedE.eDoeesnotcontain TSCA AIree H2:82-5D5a0y9:SuRedpyeaitneMdalDeosRaetsDermal Toxicity ~~ Dupont 11763 ----[ INDID VIDUALD AANNIIMMAAI LLCCLLIINNV IICCAALLPPI AATTHHOOLLD OOGGYYDDU AATTAA AL EXPLANATORY NOTES (Continued) noes: oOrnbeinTdeiasvoindsu,al1s1pinoaflhdiactha aavree nooxtplaretpaooxstaIdn,thLe sBaoyndybordecuosrdteorane of the following cansons or ttEahhVueoAsTss1aa6wrrspl.lFeeaisvanlasstsveCcctooiltucoiitsoseneutndlotrs(acnabotelnd)oSboirfaoirtnoescds.oisnt(giHnogH (15) 7t0h"estamhplEe vaesaavepirliaobrle-tofosremTiessticnogl.le(cNtOiR)on npT eernforama nedsnodnivCihdiauCisi)attohbeisoeTnrosvcaoPtraidroeindorwVaoalasuder:MectohFrodrSe.hdaoraxasrBpbieeeil,ngiLfnlobsdsIaLticaEh.uabnina cvaesrtaeipnorvsaeldu,becaohlcutolatoinonswavyere --~ -- _-- CompanySanitized. DonotecontsainTSCA CBI re ~ 3 3 oni min EB mI Hamm _ Po ommmam smog . 1I 0 EEE HEnnan " FEN FENEEREEE REE Be SEIIGNSED dEIEENEE 8% 9333533533 = 233idanis i g , daazeansas | atannn 3 H i smssssssss go sxsssssss 82 2 5 E3BERRREEE ThRusssuss `Company Sanitized. Does not contain TSCA CBI ~ Bo oineeasads (HEHEHE Homelands yp Be GEEIEIIEI J3ITNENEe -- iPr8e% oddzmsfesnsnss sdddadaamansE 3 i Br o3ddeddgdd ddddsisiie Be fdddeaddd 334sddddds Be IETEIIEEE JENNIE i Bo. dens PEEREEE Ld : 5Hoo ss mmmnan |e ! Iz . swssfrns gp gsssssses 3] i i ig i 3 8888338888 i 88LLLLBELS CompanySanitized. Does not contain TSCA AAI ~t 3 2 i 5 -- i 5g 5. $d IINEEEERT amamsaamm : BIE mamnREn # 333E33a03 HERR gv & > 2i , 2%1 gp sssiossezdndadndadsd qi i i PEE LE : S gsnsseerer BIseauRas Er : = & M EsLdTdIsIsNiTiIdTaEs 8: LEE ERE cxnsessans CompanySanitized. Doesnot contain TSCA CE) ~ zi ! 5 3 g i --_ 3ito i : PE BEE BNNNL TE Omeny 3mm Bons umn EN EE , 13033308 sasnaanen, i HHi; diisahiinang : ssaanzsinseaesnsyst i Bf 13e30830 gp mnennenan i3 #1 BEBEEEREEE sehEisiset Company Sanitized. Does notcontain TSCACB. ~8 i 8 Pera EEE pip sm ~ | 5 ie 8Ee f4rByau5md I Ti efpin elaine Ty Fea Pera i B : i 3 7 sesszreses eeesesesss `CompanySanitzed.DoosnotconlainTSCA CBI ~8 i 2 TrrrEr ng i ~ | dF& Fe a ert edm wsn pg b ; iiEs Cg [EEREREREY | ' i fbn Hiefe 3 : i i : Ii | sezefasess FRIITITTITH 7 HI i 24 2 3 $883838838%8 i 2888883838 CompanySanitized,Does notcontain TSCACBI ~8 2 2 Py theese ogee --_ gg gesd df k goo ! i: . F: .3 FE esges;ss@sgePsPEegysy Company Sanitized.Does notcontain TSCACBI z Br DBR i 8 BREE fel e fa Peg [ERREEEERS | ' ie Ee [EERE 1 iit . Ero [REEEEEREY1 2i E FE E .3 rinraen & i } $ i Bop og Es I i | s#eafassad y eeadesfesl 8 2 22 i SEEEBBEERE 3BBluvesss LompanySanitized. Does not contain TSCA CBI i --_ ; i i Bf Z3iainadel gEasdsasas NEHER E : BEEREERES : gaeeaeases 5, i : gaagesast ; BaegaEseny EB i ; HEHEHE : HEH HEH sem ~ z3 ~: i 2 ir i i ~~ iz Poo omaman Faiiaaiand oF mE mena io. BEEBEEEENY C nenemmmamg E : : ggesesenss i HHH HH 7 gmnnnnnn faggensans ii f EEEEREEEEES Dissssann i i B8EE3EE35E i EERE CompanySaniized.DoesnotcontainTSCA CBI 8% sossasssar ssessaszes 8 omeRAER aamaaseass 8} samazssszs goszsasess $F4E8 3anE3gmEadtaEaEnEn aaf%EaasisissuEasss 3 TeoonmmEn sums j i 3 EH 8ITRRERSIH EERE 5 323333288: 35%s288%e , BEERERERNS - pmmaEmEMS 5 3 i Ll Pop EERRREMLN < mpmpnamen a5 Ii z . ERO | EEE HE 7IER EH EFa H i 3 f sesssnsss Foecersnnas `BompanySanitizod. Doosnotcontain 5h gy 8 23E3IRRTILE RARRRLIIRA B#p8 J233934343%d3d3eRlAs% E4E%%3R%3%E%4 i 2ams3nNaxs anizgensan f: 3 m$esiseesessds sJeIeSnEiiaSaeadaYd. ~ D3 mmesmaamr msnsssash i : % i! $5 saszgeeass OTE | 5 33258=038s3 aszsazgesd& oo BEEIEEEENS smmmmmMEE z z : is i Eaiagfases i fapaneys i : FAIR 5 nugag `CompanySanitized.Doesnot contain Ta cr _ J ig if I : i2 j 3R%IIIEEET EnmnasEans fF]8 ssemmdmdcicnadnassa ssietnisdnesnsaiagn Pel means ssa 98 EEE mE i 88 samamnamn snanaanaa # onwmmnm wamnn i : ed 133330333 e $333032332 2 z ggsp p FosaH.sERe 2 feskiefsis 8% 7 sesssaauss g wxsnasacas 2 22 souBEBEsil 88333E5EEE Company Sanitized, Does not contain Toa Ant ~f i mmm mang | de mmm simp i : z G83 Emma gamma 3 . ) i8 mam moanagsed: 3 mwas gamaesysd 1] | ou! {respa 2 8, 22959022 venunennad E, 3 5 sesenazzes esgmsszasy 2 B g 1FE F52r8 5 menemsessezse g& seRsnieseri `CompanySanitized. Dasa nat ramiain Tons ane Bompanysanitized. Does notcontainTSCA car ; ~| ; 8 $333333335 s33sssse: | fmm onan 5 Bj BERNE: MEIIMANE B5 r Ci em - mn Eompany Santized.Doesnotcontain TSCACat ~f : : Hmmm $333333ass Poo Ennpnamane ommnmmam 4s 7 8p nnn}: one I PC BN GEN Eompanysanitized.DoesnotcontainTscA cay 88 snmanasan snanaaoam Edna ; | fBEEEeatldEEnEEEEEE tBrEeERsEsNNeEsE FRR OPTTRHTT tii ~ | if HIHGE Eh : is 2123223030 Rn : i gaigeRnisd Pesgesspas Bo Gum dein Ff, Saddam. 3REEEEEEES = > & ii o&o HHH i v n EE TR Es . ZRHERENEEH R SREERSSERS 5 ad ssaazsreer seseezasas CompanySanitized.Does notcontain sea rar } 83 3322333333 3333333313 EE] gEpEsEsEaEsEsEg BE Eseuosieargipgpty OE 58 EBEELJEEEEBREEEEEEEE EEBpEEEEEEEEJ.EEEE 88 I] ~ PROD GE 5 ii rrissene:s 223305 Bg 2I233R%33 3d:ddacais ia Lo SEIN 2 HE5 N Company Sanitized.Doesnotcontain Tra mar ~ ww a=i 42 3 ~ :i i: z [1 ELE EEE E EE EEE Z 8 : g > & 2a $3 % Bog esuEREAgRs TRUASUNARD 3 Srgnamaman ANSAKERE=S 3 i : `EtpanySanitize.DossnotcontainTSCA my 33 PN i3 i. I : i 38;p ess3ssm8saesassmecss [J Ens3wafess FE] Fi 53 8 2 1 ineeny, wen Sompany Saniized. Doosnot contain TSCA CBI ; i I ~ ii i 3 i QAR stung ie unfing saree i EEBeBEESEE GEERERBEEE Bo, BBReREnene : HHH Lv mmesnsnens ; common Bo ue: ann 27 i ARAAANORER AHOREARAST `Company Sanized. Dossnotcontein TA 75H i is ujepuil] snafu ' i unfree stasfesne] | EEEREEEEEE cRREERSREE LIPS EEE EE EE I : i og aRebien fern i EL I; ann a3 i SEBEEBEEEBE SsEBssEis Company Sanitized.Doesnot contalnTRRA ~=t 2H5--2D5a5y09StRuedpyeMiantMeade-lDeoRseaetsDermal Toxicity --_ DDuupoent-m11i763s -- APPENDIX H Individual Animal Final Body and Organ Weights Company Sanlized. Doesnotcontain TScacal E ~ gimme | Sains 1pm Ean : ~ 5 ipdiddscdsisic sii [gf ddfasasi 8 {Sgisasaenases sal (Gy isgrampes! $ 3 [LEER BE CREE 1] ifn dian . Fraime Ef seme e I~ i ssaveenn5n3s) 8 izeensamni i BIEEFEREAEE 531 4! sy gsasEsEn 3 37g AENENNEER ER 30g Enanamn "CompanySaniized. oss otcontain TSCA CBI ~ g3 z K{7I5xEaRgi i] | 3izeaeessnen ur E pliseeal p| lssaresnssnscs asagi Simi ie ER I ~ 8 EpEE AE fe amma ag : 3 EBmEaAm EIsAmEeA aRl ' i gSimaz g maompmEawn ggEoRbiE SgiieCsR 58TI (3p zasyzanans Fama E3R7] 3 CREE plEnin i i i HE rrereti Ld Prrerrrrrrapr : DE ch fT i ESL gE EERE I 5 companys `Doesnotcontain TSCACBI ~ 3 3 [rfrrerrrerrear | Bidsadaasess a g Joma ~ . i Bl i 4 ~ gids i FiEIEEIRAREE A yet Po pam 8 {BY | aeRguaoarE ua 2 {EB isznsszasEn AF EE isosassaes sn i naman mm 3 pdiSRetERERRI RE B 18 | Sensarayes Zoi BF Hisueiamseiini oo | H-- EE -- fhm sn HERR Pomme iy amsmsmanar HgiEf R|EBESESEGEEEERE if . 2 ' i 5 i i: Gompany Sanitized.DoesnotcontainTSCAC8 ~ti: g poe pen 3 Bommn pon : % |Jplimumasemnisis )spl |Dp aomseaEsnE : 2 55 Py - tlhgoiogsmasmizmsanes agsi haan fig. gigasazai 38 sigids @9f ai Bieddddeas) 2 tig essseeeees Cp lmeesasl : [CompanySenitized.Dosshotcontain Tara FRY g Z| z {gina asi | ginedudsesdn a3) POEL es } JOE EEE 0 gmn dmmes : ; BE pumama i iim eg gl glsememmanxnge 1 Pigeon fi fiasmnaniess ol loorp g EeE Gdr paEEmEReEHE il Thm mma EompanySanitized.Does notcontainTSCA FR ~ 3 2 dssoeeeeoeo | gissasamsiss op) 3 REET 2 0 Leesee Eg opegeuisans ap fame : 5 R iocadasddsd 34 ig ammseaemn un) op : Bi" EEEEE izzesazesss 33! i5 3 i7_isesssssse t `CompanyStas Docs nfcontin TSCACE: H2-62-5D5a0y9S:tRuedpyeiantMeadl-eDoRsaetsDermal Toxicity -- DuPont 11763 --~ APPENDIX I Individual Animal Microscopic and Macroscopic Observations -- Company Sanilized, Does not contain TSCA CBI EE F2-62.5D5a0y9S:tRuedpyeiantMead-lDeoRsaetsDermal Toricity DuPont11763 INDIVIDUAL ANIMAL MICROSCOPIC AND MACROSCOPIC OBSERVATIONS -- EXEXPPLLAANNAATTOORRYYNNOOTTESSS LesionGrading Hainsdtosepvaetrhiotyl.ogTichael dcihsatnrgiebustaiorne (deexstcernitboefdtaicscsourediinnvgotlovethmeeinrtm)oirspihnodliocgatiecd,chwahreacrteera,ppdriosptrriibauttei,obny `ampopdriofpireirastes,ucishaalssofoacsasli,gmnueldtiafsocfaoll,lodwisf:fuse, unilateral, bilateral, etc; A severity score, if Minimal: the normal limits amountof change present barely exceeds that which is considered to be within Mild: in general, the does not produce any lesion is easily identified functional impairment. butoflimited severity. The lesion probably * LMiomdietreadtet:isstuheeolresoirognains dpyrsofmuinncetnitonbuistptohsesrieblies.significant potential for increased severity. Severe: intensity the or degreofchange i either as completaes considered possible extent to expect significant tissue or organ dysfunction. or great enough in ~ `Comment: grades minimal through severe represent progressive involvement/severity along a continuum with minimal lesions being the least severe and severe lesions being the tmhoesytaslesvoerien.dicWahtieltehetihrergelraatdievse rbeifoelrogtioctalhesmigonripfhioclanocgei.cal characteristicsoflesions, Gross observations (iea,b, c,d, etc.) listing multiple masses fora tissue are distinguished with lotters ~ --_--_-- `Company Sanitized Does 101" grams cal Tiss 28F.-2D5a5y09S:uRdeypeiantMeda-lDeaRsaetsDermal Toxicity DuPont 11763 ~~ INDIVIDUAL ANIMAL MICROSCOPIC AND MACROSCOPIC OBSERVATIONS Dose Group: I 0 masks Sex: Males Animal Ref Microscopic & acroscopic Findings series TKoirlmliendalonSDaacyrif: ic25e Animal ia signed off from necropsy Gross patholosy : No MaLAcIOVRrEToRAs,,copKBiRIADcINNEA,YbSn,oSrPmILaNUlNAGiLSt,yCORHODEb,AsReTrS,TvOeMdSAKCE+HL,ETADLUODMEUNSUCML,E,JSEPLSEURN,, ANIDOLDREEE,N,A|LSAPGLALINACVNRADERSAY,S,GLSACCNEIDCASU,TN,CMCNAOENLRDVOIENB,,ULAPRREICTTLUUIyMT,AeRYMNEGOSLDEEAN,NTDE,TRHIYCMULSY,MPH TSPHEHYMARIRONYIANDLX/GVLLEAASRNIYDCY,L,ESB,EAYREUA(RTSIH)NYARROWTYIDTHBLGALODAPDNTEDIRSC,. NETTRERVSAETC,EHSE,AS,KIENEP.SIODPPIHRDAOWGSIUTDSAE,TSE,, PENUR/XNEE GOINT, STERNM, NOS Histopathotosy wLaevaeINPLAINTION, SUBACUTE/CHRONIC, FOCAL, minimal. --_ NANDI`BEDRUEYLGTAEHRNAEGLRCYAYMTIIPOOHSN,IHSO/MDEYEORPYITSHERRO,PHAFGOOCCAYLT,OSmIiSn,imamlinimal. PARATOHNYEROOIFD AGLAPNADISR P: RESENT. 667165 Continued on the next page... --- CompanySenitized.DoesTniostec-ontainTSCACBI B2H-8D2-5D5a0yS9S:tyRuedpyeMiantMeeadl-eDoRRsaeetsDermal Toxicity DDuuPonwt-1i176}3 ~ INDIVIDUAL ANIMAL MICROSCOPIC AND MACROSCOPIC OBSERVATIONS Dose Group : I 0 ng/kg Sex: Males Animal Ref Microscopic & Macroscopic Findings S615 Continued from previous page Histopathology + No MSKiIPcDIrNNoEAsYLcSo,pCOiRcLDU,NAGtSSo,TrOmMSaAKlCEHiL,tEyTADLUOObDMsEUeNSrUCvNLe,Ed,J:ESJPULNEUEMN,, AIOLREGTNA,, BPRAANTCNR,EAS, `GCGBLLCAAUNNMDD,S,, CTHOTYLHROYON)I,DS',RSGCLATADONRNDE,,NALMPEASGRELANATTNHEDYRSRI,OCI.DSCLGIYLMAAPTNHIDCSN,ONDEERT,VREA,CSHAEPLRII,TVUAIRTYARY EPSRSPOOISPDTHIAADTGNEUN,SI,DESSPE,HIANRFAYRLINKUV/REL/SAKIRNCYELNEEKS,J,OIENUYTRE,(ISN)ASRTEYWRINTBUHLMA,DODPETBRIO,CNETNESNRSAVTREER,SO,W,SKINNO,SE, SKIN, TRENTED, SKIN, UNTREATED ser16s TKeirlmliendalonsDaacyrif: ic26e Animal is signed off from necropsy Gross Patholooy : ~~ No MAaLcIOVrREoTRsA,copKBiRIADcINNEA,YtSo,SmPaLIUNlNAiGLtS,yCOROHDEb,AsReTSr,TvOeMdSAKCE:HL,ETDAULOMDUESNCML,E, JBSSPULNEGENN,, ANIODLDREEUE,MH,ALSPAAGLNLICAVRNADERSAY,S,GLSACCNEIDCASUT,KE,CMNCAEONRLDVOIENB,,ULAPRERICTELUUYINMT,PARHYMNEOGSDLEEAN,NTDE,RTIHYCMULSi, b PTSEHHIYAIRRNOVAIALD/LGVALERASYNINDCK,L,ESP,EAYRBUA(RTSIH)NYARWROIYITDHBLGALODAPDNTEDIRSC,, NETTRERVSAETC.EKSE,RS,KIZNPE,ISDOIPPDHRYAOMGSIUTDSAE,TSE,, FRAUR/KNES JOINT, STERWM, HOSE 667166 Continued on the next page .... ~ _-- CompanySanitized. Dossnotcontain TSCACBI iT: B28FD--2D5aw5y09SS:tuRudedpyieantMeadl-eDRoRaseetsDermal Toxicity DDuuPoonmtl11r76e3 ~ INDIVIDUAL ANIMAL MICROSCOPIC ANDMACROSCOPICOBSERVATIONS Dose Group : 10 na/ks Sex: Males Animal Ref Microscopic & Macroscopic Findings wries Continued from previous page Histopathology : LKrvDemEINFLAGIATION, SUBACUTE/CHRONIC, FOCAL, minimal. MANDIBCUHLRAOR.NICLYMPPRHOGRNEODSESIV:E NEPHROPATHY, minimal. PARNTEOHRNYYERTOHOIRFDOCGAYLTAPONASDITSRS/P:ERREYSETNHTR.OPHAGOCYTOSTS, mininal No MLCiOUcRNrDGo,Ss,coSpTHiOEMAcRATCA,Hb,noSrDKUmEOaLDlEEiTNtAUyLH,OMUbSsJCeELJrEUv,NeUdNS,P:LEIELNE,CH,AORPTAAN,CREBARSA,IN,CBOSUPMI.NAL CTTOHVLYORSNO,I,D"RGAELDCARTNEQDNN,,ALMPGEALSRAEANNTDTHSEY,RRIOCISDCILGAYLTWAIFNCHDSNN,OEDREVT,ER,ACSKPAEILRTI,UVIATRBAYSROPYGHLAAGGNLUDASSN,,D, PSFUEEAUNRIUYNRNA/KLK/NLVEAEERSYIJNCOKLI,ENST,,EYEUS(RTSIE)NRARWNYI,THBLBAOODVPDETEIRMC,ARNRETOREWVS,ET,ESN,OSSKEIE,NF,DIPDRWOISTDAECSE,, SKIN, TRENTED, SKIN, UNTREATED ~ ssmer KTeirlmliendalon sDaacyrif: ic38e Animal is signed off from necropsy Gross Patholooy No MAaLOcIRVrTEoARs,,copKBiRIADcINNEA,YbSn,oSrPmLIUaNNlAGiLSt,yCORMODEb,AsNeTrS,vTeOMdSAKCE:HL,ETADLUCDMEUNSICNL,E,JESSPULNEOEMN,, KAIODLDREEUE,MN,ALSPNAGLNLICAVRNADERSAY,S,GLSACCNICDAUSTM,I,CMNCAEONLRDOVINEB,,ULARPREICTFLUUYIMMT,EARHYMNEOGSDLEEAN,NTDE,TRHIYCMULSy,WrH 667167 Continued on the next page... -- -_-- CompanySanitized.Dossnot conteln TSCA2 Tse ZD128u2-5yD5Sa0y9uS:tdRuyedpiyeimantMeMad:llDeeoRsRaetasDsermal Toxicity D DuPow nt117g 63 ~ INDIVIDUAL ANIMAL MICROSCOPIC ANDMACROSCOPIC OBSERVATIONS Dose Group : I 0 mg/kg Sex: Nales Aainal Rot Microscopic & Macroscopic Findings serier Continued from previoss page Gross patholosy No M`aPTcHHrAYoRRsOYcIIoDEp/iGcLLAANARDmA,o,rPmEAaYRlEAi(TStH)yYROWObIIsTDeHGrLvOAePNdTDISC:, NETRRVAEC,HEAS,KINE,SOPFHRAOGSUTSA,RE, FSEENNUIRNA/LKNEVRESIJCOLIENST,, USTREIRNNAORMY, BLOASDEDER, TESTES, EPIDIDWIDES, Histopathology : MLAaNvDeIBIUNLFALRINLOYTHIPOHN,HoSDUEBACUTE CHRONIC, FOCAL, minimal. BARKEEROIYIERTOHIORDFOCAGYRLFOAASISIRSP/+ ERREVSTEHTR.OPHAGOCYTOSTS, minimal Yo MKBiRIcADrINoNEs,YcSo,pSiPcLIUNNAAGLbSn,oCOrRmHDEa,AlRiTtS,yTOMSOAKbCEsHLe,ErTvDAeULdODWEUNSGCML,E,JESJPULNEGEMN,, AIOLRETUAM,, -- PSPAIANTLCUIRIVETAAARSRY,YGLGCLEAACNNUDDMS., TTCOHHLYYOWRNUO,SI,DREGACLDTARUWENDN,,ALPMGAELRSARENTNDHTSYE,RROIICSDCILGAYLTPAIHNCDSNN,OEDREV,E, EUTYRREAI(CNSHA)ERAY,iBLmBASDODPOEHPRAT,GIUCST,ENSEPTRREVASER,,YISBKKP/IINCD,AIDRYYPNNRIODSETSA,TE,FEWSUERN/IKNNAELEVEJOSIINCTL,ES, STERN, BONE MARROW, NOSE, SKIN, TREATED, SKIN, UNTREATED ~~ -_-- ompanySanitized. Doesnotcontain TEGA 0B Ie A H2-82-5D5a0y9S:Rtudey pineeMaaleetRaetDsedrm-aDlTooxisciety DDwuoPonnti-1i17e63 ~ INDIVIDUAL ANIMAL MICROSCOPIC AND MACROSCOPIC OBSERVATIONS. Dose Group : I 0 ma/ks Sex: Males Animal Ret Microscopic & Macroscopic Findings - Serica KTielrlmeidnalonSDaacyr:ific2e8 - Animal is signed off from necropsy Gross Pathology : No NLAaIOcVRrEToRAs,,copKBiRIADcINNEA,YbSn,oSrPmILaNUlNAGiLSt,yCOROHDEb,AsReTrS,TvOeMdSAKCE:HL,ETADLUODMEUNSUCML,E, JESJPULNEURMN,, ANIODLDREEUE,MN,ALSAPGLALINACVNRADERSAY,S,GLSACCNEIDCASUT,NI,C`MNCAEONRLDVOIENB,,ULARPREICTTLUUYIMMT,PARHYMNEOGSDLEEAN,NTDE.RTINC SL,abi TSPEHHMYAIRRNNOIAIOLD/LGVALERASYNIYDCK,L,ESP,EAYREUA(RTSIH)NYARRWOYIITDHBLGALODAPDNTEDIRSC,, NETTRERVSAETC,EHSE,AS,KIENSP,SiODPPIHRDAOWGSIUTDSAZ,TSE,, FEMUR/KNEE JOINT, STERNUM, NOSE Histopathology : LrvenIN: FLAMMATION, KIDNEYS: SUBACUTE/CHRONIC, FOCAL, minimal PARATCHHYRROONIIDCGLPARNODGSRES+ SIVE NEPHROPATHY, minimal. ~ vos MISSING. MTEHTFALPALDAISAITAI,ON,SQAUCAUMTOEU,S, EPEIPTIHTEHLSILAILO,N, mmiinlidm.al 667168 Continued on the next page .. --_ -_-- GompanySaniized.DoesnotcontainTSCA C81 160- H2.82.5D5a0y9S:uRdepyeianteMdi:eDoRsesDermal Toxicity Dupont11763 --~ INDIVIDUAL ANIMALMICROSCOPICANDMACROSCOPIC OBSERVATIONS Dose Group + 1 0 marks sexs sales Aina nef Sicroncopie & Macroscopic Findings Gris Continued from previous pase Histopathology o MCCiLOcONRrLCDoOS,s,,coSpTE"RiCAEucCSATEICaO,HNb,,mSoDMKrEUEaSOLlEDENiETTNtAEAyLRLI,oVCUb,SSsGeLELrIRIvN:eNEdS,PKLOEDTERL:N,RS,AALOTBNAUENA,CRRYEBRRSSAe,DnVo,Cro.SoP:IN BSNSAEOERDMVRIEIS,RNULFLAVIAERTSORILLKCIYLI,NERSEY,EGRYOUELD(REaST:),IOWTYTREYOLBNRLSOAO,LDPDDRAIRGD,LRAENNETNDRRA:VSLEF,ETGSLR,AASNCKDHENSEB,,Ai,DSPIhLEDOeNVOoRTpBLAaEACNSDG,,US. CFREEMAUSERSS JOIN, STEN, BONE ARRON, SKIN. BABARERL iN, crammsAwToRr OsLoDwiCeams series STXneiirTrmTaielndalo5n3sSDaeicyyrinfe+ idc58eoct trom necropsy Gross Bathotogy ~ Ho MBaLTcOEErRREoAs,,,copKBEiRIAADcRLNCNERA,YEbSAm,SoS,rmLRUCaNRAlGCiSUt)MyC,OROWDECb,AOsKLeDOrS,NvR,eONdSAAKCSB:HCL:TSOTNA,DLUOMMDUEESSNCBOLHN,EF,EAILBSGseOLLnERma,,i RROODREE,ALSAGLLIAVNADRSY, GSLCAISAT,ICWNAENRDVIES,VLARPLTLUYTMEPAHRYFGOLEA,ND,Seve 667165 continued on the next page -... ~ Sapized. Dossnotcontain1ACE -_-- H2-62-5D5a0y9S:tRuedpyeainteMda:lDeoRsaetsDermal Toxicity wDuPeont1n176s3 ~ INDIVIDUAL ANIMAL MICROSCOPIC AND MACROSCOPIC OBSERVATIONS Dose Group : 1 0 ng/kg Sex: Males Animal Ret Microscopic i Macroscopic Findings erie Continued xen previous page " " Gross Bathology : Yo MTaPHcErIAoRRsYOIcIEoD/pLiGAcLRAYNAYDbX,m,oEmEAaVRlAAi(TStH)yYRWOOIbITsDHeGrLOvAPeNTdDISC:, SBIAL VESICLES, URINARY BLADDER, NETTERRSVATECE,HSE,AS,KIENPE,ISOOIPFDHRWAONGSIUTDSAE,TSE,. FERMUR/KNES JOINT, STERN, NOSE Histopathology : MsAoNwDoIsBHUELMACRRILUYGMEP,H ARLOVDEEO;LAR, FOCAL, minimal PARAETRwHViYTsRsHOIRIvDOGC,GYLTAONSIDSS/:ERYIHROPHAGOCYTOSTS, minimal. Esvreo(ssT)OaPTTErICmNGErRrVrEcNwOTERvPeRESENT. INFLROINTION, SUBACUTE/CHRONIC, FOCAL, minimal. ~~ Ho MiLBcIRVAzEIoRNs,,coKSpIPiDIcNNEAAYLbSn.CoOrRmHDEa,AlRiTtS,TyOWSOAKbCEsHLe,ErTvADeLdODMEUSNCML,E,JSRPLSEMEN,, AFOLRETUNA., PSPAIANTLCUIRIVETAAARSRY,YGCGLELACANUNDMDS,!| CTTOHHLYUORNSO,I,DREAGLCDAIRNOEDMN,,ALNTRGEALSCAEHNNEDTASE,,RICSSSCOLIPAyRTAIiGCUSNO,EDREV,E, JVPOEEISANIRTWC,ILOESSS/,TLAEURRYRNINKN,,ARYBBYOBENL(SSA)DNDAERWRRI,OTWH,TEOSNFTOFSEIESC,, NESERKPVIIEND,,IDSTNKRIIEDNNE.TSE,DS,EFNSEIKNNIOANRL,/AiES 667269 Continued onGtRhAe TneExDt page .. --_ CompanySanitized.Dossnotcontain TSCA CI _-- mr -s H2-82-5D5a0y9S:tRudeyipnMealaeRtatesDedrm-aDlTooxisciety DuPont11763 ~~ INDIVIDUAL ANIMALMICROSCOPICANDMACROSCOPIC OBSERVATIONS Dose Group: I 0 mg/kg Sex: Males Aninal Ref Microscopic & Macroscopic Findings se7160 Continued from previous page Tr Histopathology : ORGANPSARNAOTTHYERXOAIMDINGELDA:NDS s67170 TKeirlmliendalonsDaacyrif: ic30e nial io signed off from necropsy Gross pathology : No MLAaIOcVRrEToRAs,,copKBiRIADcINNEA,YbSn,oSrPmLIUaNNlAGiLSt,yCORHODEb,AsReTrS,vTOeMdSAKCE:HL,ETADLUODWEUNSUCML,E,JBSIPULNEUEMN,, ANIDOLDREEEU,MN,AL'SPAGALLNTACVNRADERSAY,S,GLSACCNEIDCASUT,NI,CMCNAOENLRDOVINEB,,ULAPRREICTTLUUYIMMT,PARHYNNEOGSDELENA,FNEDTRHIYCMULS,PH TSPHEHYMARIRONNIAODL/LGVALERASYNINDCK,L,ESP,EAYREUA(RTSIH)NYARWROIYITDHBLGALODAPDNREDIRSC,, NETTRERVSAETC,EHSE,AS,KIENPE,ESDOIPPDHRYAOMGSIUTDSAE,TGE,, FEMUR/KNEE JOINT, STERNON, NOSE ~ Histopathology : vxeeownEyIsNFL:ADINTION, SUBACUTE/CHRONIC, FOCAL, minimal HEARTCHRONIC PROGRESSIVE NEPHROPATHY, minimal. 667170 Continued on"DtEhGeENnEeRxAtTIpONa,geMY-O.P.I-BER, FOCAL, minimal. --_ CompanySaniized.Doesnotcontain TSCACE! TT ---- L0 12b52.o5D5ya0ys9:SuubRdeyipeionaMtMeaidl-eeDRRoasateDssermalToicty oDuwpon1e176s3 ~ INDIVIDUAL ANIMAL MICROSCOPIC AND MACROSCOPIC OBSERVATIONS Dose Group: 10 pa/ks sex: ales frome Niceoscopic & Masossopie Findings Gin Continued trom previous pase Histopathology : sEroREATrRIOsRLDOsCGILeTAODSEo1SpBeRVT HROMIAGOCYTOSIS, minial. re No MSRiNEcTGCrUTSoINs.NcG,o,pSiNKcDEESLOAEENTmOTAoELDrRm,LMaIClSiCSLtLyEEyvC,iOoSbNENs,LoeRorkMvT,NeL,dESAA,OLRITVEAAA,RRYCRSELRAAASLD,Y,SC.SheETrAmaLoCscoorxnp,, RAGEDLVRA(TED3N,)AA,TWHGBIAATCAIHDETOSRF,,,LCSBTCSHNIOGENMTRTAHVIGSECU.,SN,ESSRRKVIBEDA.:IADRIIBPNARAEROTO)SOLEETSAAT,TADRR,YYFE.NS`OLSRAEIMAMSNI,RNEM.vaSvaeosanitcehuss, STERN, OTE ARRON, NOSE, SKIN. REARS, SAN MeRMAfED cramEsRawonrRossoswSna:ms --- conn FATeiedlralmdeildnalo8nsDSaaicyirnietai's3o8ett trem necropey Gross vathology No MLHaIIOcLVRErETDoRALs,,,copRSFiINADVcIUCNERA,YEmSRo,SSr,5miCaCOiAOMiCLEtU,NyC,ORoHDECb,AOsRLeDOrS,Rvh,eodSuRKABRc:CLHTECTHAD.LIODWMEIENSSGCGHLH.EE,RSLSSEERsLN,,H 667171 Continued onHSTDOhBRe,En,SerAGsLILpVaoADnRsSY', GLSACNIDNS,LCNANNEDRIVBES,LAPRI,ROLTYIMAPRHYOGBEe,aOVE f companySaniaiznetd.ized.DDoss otcontinSCAC2 -- D2D285o-5DS0ay9uS:tbuRydeypnienMstMida-elDeroRsasetssDermal Tosicty wDupeont1n176s3 ~~ INDIVIDUALANIMAL MICROSCOPIC ANDMACROSCOPIC OBSERVATIONS Dose Grow + X 0 masks sex: ales Tnisal Raf Hicroscopie & Macroscopic Findings pre Continued from previous page Gross Bathology Ho M"aPTcARrIoRTsOAcIoD)pLiGALcRAYNAIDmK,o,mPmEAaYAlETiSAt)NyROWoTbEDsPeGrLOvAPeWTdDISC:, SEUINAL VESICLES, URINARY BLADDER, NETTRERVSAETC,EHSE,AS,KIENEP,SIODPPOHRAASMGCIURGSRE,FLE,, FRR S01iE, STERN, HOSE Histopathology : KLarvoenneIrNFLAOIATION, SUBMCUTE/CHRONIC, FOCAL, miniral. FHRAONSDTIAEECTHVERLROANR YICLiTPeRnHOGNRROEDSEGESRIYVC TEHYRNOEPHTHRAOOGPOACSTYITYTO,STSSm,inmiimnailnal. 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TESTES, BPIDIDYMIDES, Histopathology ALNaDvIeBnUI:LNAFRL,ALTIHOPN,NODSEUBNCUTE/CHRONIC, ROCAL, minimal. Ps PARATHEHYYRPREORIPDYLAGSLTIAAN,DH1SSLW+REMRPYROTOHCRYCOTFEH/YAPGLOATSRWATOIoCSYSTE5,, mmiilldd.. ONE OF A PAIR PRESENT 667172 Continued on the next page .. ~~ -_-- Company Sanitized.Does notcontain TSCAC81 ZD21y625DS5a0uy9l:StyRuednpyeMianteMeidel-eDloRseeassDermal Toxicity DDuPou nt.11e 763 ~ INDIVIDUAL ANIMAL MICROSCOPIC AND MACROSCOPIC OBSERVATIONS Dose Group : I 0 my/ks Sex: Males nial Rat Microscopic & Nacroscopic Findings ns Continued from previous page Histopathology : Yo MKSiRIcADrDNoNEs,YcSo,pSiPcLIUNNAAGLmSo,CrOsRHaDEl,AiRtTS,yTOMSoAKbCEsHLe,ErWvNeDLdUMDUSECL,E, IBSPTLIENENN,, ATORRTHA,, PSPAIANTLCUIRIVETANARSRY,YGLGCALBNACDNUSDM,,, CTTOHHLYOORRNOS,T,DRAGEDCLTRAOEDMN,,ALMSGEALSRAEANNRDTISEY,RATOCTSDCLIGRYFLNLAECNH,DSNN:OOORRW,E, UTESRYRTIRAE(CNSKRA)ERNRY,,IBTLEBHASODONDPEOERPRAWT,GAIURCSRT,OENRSE,TRPEVASEN,,ORSIEBS,KEIILNDSA,KIIKDNYIP,MRNIODSTETRSAE,TAET,EFDE,MSUERSMKIKINNNA,ELEVUSEMSPIROCELNEISE,D smn ATKnieilrnlmaeildneionssDsaiacgyrnief:dic36eoff from necropsy Gross pathology + --_ Yo MAaLIOcILRVrTEEoARs,!.coBKpFRIiRADIcINCNERA,YEbSAn,SoS,PrILmiNCaNEAlGCLiSUt,NCy,ORONDCEb,OAsLReOTr,NSv,TeOdSNRKAEEG:CHLT,EUTMDA,ULODWMEUENSSGCENLN,ET,ERoIRSCPsLmELeEVnNM,,H NATODHDRYEER,NOAILDSAGGLLLIAAVNNADDR,SY, G`LPSAACNRIDANSTTH,LYCRMONAIENDRDVGIELB,AUNLDAPSRL,TULTXLRTAAMCRHYENAOG,DLEA,NBDS,OmPoRAnGU.S, PSFHERAUARIUYNRNA/KLR/ELVASERSYIJNCOKLI,ENST,,EYEUS(RTSIE)NRANWRAIY,THBLNAOODSPDETEERC, NETREVSET,ESSKIENP.IDPIRDOWSIRSAGGSE,, 667173 Continued on the next page ... -- `DoesnotcontTSaCiACnE Company Saniized: T TTT T eee H2-82-5D5a0y9S:tRuedpyeiantMeadl-eDoRsaetsDermal Toxicity DvuPoants1176e3 --~ INDIVIDUALANIMALMICROSCOPICANDMACROSCOPIC OBSERVATIONS Dose Grow: I 0 mg/kg Sex: Males Animal Ret Microscopic & acrascopic Findings sein Continued from previous page Histopathology : LeiveyRIN: FLRGITION, SUBACUTE/CHRONIC, FOCAL, minimal. 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No MCiLOcURNrDGo,Ss,co'SpHTiEOAcNRATCAH,b,noSrDKUmEOaLDlEEiTNtAUyLM,OMUbSJsCEeLJrEUv,NeUdMS,P:LEIELNE,UM,AORPTAAN,CREBARSA,IN,CECSUPNI,NAL CTTOHHLYYOMRNUO,SI,D'RAGELDCARTNEUDNN,,ALMPGAELRSAAENTNDHTSYE,RROIICSDCILGAYLTMAIPNCHDSNN,OEDREVT,ER,ACSHPAEILAIT,VUAIRBTYSAORPGYHLAAGGNLUoASGN..D, `FPSEHEMAMURIRINN/AKKL/NLEVAEERSAIJNCOELI,ENST,,EYEUS(TRSEI)RNNAURWMYI,THBLBAOODPNDTGEIRCM,ARNRETOREWVS,ET,ESN,OSSKEIE.NP,IDIPDRVONSITDAETSE,, --~ SKIN, TREATED, SKIN, UNTREATED serra TKoirlnlienda)onsDaacyr:ific26e Aninal is signed off from necropsy Gross pathology : No MLAaIOcVRrEToRAs,,copKBiRIADcINNEA,YbSn,SoPrImLNUaNAlGLiSt,CyORHODEb,AsReTSr,TvOeMdSAKCE:HL,ETADLUODMEUNSUCML,E, JSEPTLUENEONM,, 667174 Continued ANIDOLDREEUE,MN,ALSAPGLALINACVNRADERSAY,S,GLSACCNEIDCNSUT,NI,CMNACENORLDVOIENB,,ULARPREICTTLUUYIMMT,PAHRYMNEOGSDLEEAN,NTDE,RTIHCOULS,yi on the next page... --~ CompanySanitized.DoesnotcontainTSCACBI Ties- H2:82-5D5a0y9S:tRuedpyeianteMda-lDeoRsaetDsermalToricity DuPont11763 oy INDIVIDUALANIMALMICROSCOPIC ANDMACROSCOPIC OBSERVATIONS Dose Group: 1 0mg/kg Sex: Males Animal Rat Microscopic & Macroscopic Findings saniaGross PatholoaCyont:inued from previcss page - Yo MTaPHcUrYAoRRsVONcIXoD/pLiGAcLRAYNANDbK,n,orBmBAYaRElA(iTStH)yYROWObIIsTDeHrGOvLPeATdDISC:, SENINAL VESICLES, URINARY BLADDER, NETTRERVOAETC,EHSE,AS,KIBNSE,SIODPPIARDAOWGSIUTSSAR,TSE,, FENUR/KONES JOINT, STERNOM, NOSE Histopathology + LriavveerRsI.N+ FLAWATION, SUBACUTE/CHRONIC, POCAL, minimal ronsC;HRONIC PROGRESSIVE NEPHROPATHY, minimal. HEARPN+ EUMONITIS, ACUTE, FOCAL. minimal. MANDIBDIUENLGFAELNRREORLNATHTIIFOONN,,ODWSEYUOBPAICBUETRE,/CHFROOCNAILC,, mPiOnCiAmLa,l mininal EHYPERRELYASITA,H1SL)YREMRPYHOTOHCRYCOTEP/HYAPGLOTACSYMTOAOCSYISTSE,, mmiinniimmaall. ~ Ho M`iSScKTrEOoLMsEATcCHAo,LpicXMUISOACDbLEnENo,UrNm,aSlPJLiEtBEyINU,ONbNAs,OeRrTvIALe,EdUMS,RAIPNA,NCRSEPAISN,ALCBCCOORMD,, COLON, AGRLDEACRNTEDON,NA,LP`GAMLREAASNTEDHNSYT,REORISIDCCIGALLTYAIMNCPDHSN.ENROVDTEER,,ACHSPEAIALT,IUVIAETRSAOYRPYHGALGGALUNASDN.SD., TTiHiVaRoOg.L 667174 Continued on the next page . [EompanySanitized.Dossnotcontain TSCA CBI we 261-2D55a0y9S:tuRdeypeisntMeadl-eDRoastesDermal Toxicity Dwupoen-1n17t63 ~ INDIVIDUALANIMALMICROSCOPICANDMACROSCOPIC OBSERVATIONS Dose Group : T 0 marks sex: vales Anival Rot Microscopic & acroscopic Findings i} pen Continued from previous page Hiscopathotogy Ho M`SFiPcEHIrIAoRIRsTAcILEoOGp/SViLEcASRIJAICOmNLIXoEN,rSTs,,BaYlSEUi(RTStIE)yNRANRWoYIb,TsHeBLBrAOOvDVPeDETdEIRNC,ARNRETOREWVS,ET,ESN,OSSKEIE,NA,DIPDRYOISTDAETSE,, SKIN, TREATED, SKIN, CNTREATED -- --~ - ------ CompanySaniized.Does notcontain TSCA CF: Tm H2-82-5D5a0y9:StRuedpyeainteMda-lDeoRsaetDsermalToxicity DuPont 11763 --~ INDIVIDUAL ANIMAL MICROSCOPIC AND MACROSCOPIC OBSERVATIONS Dose Group + IIT 5 ng/ky Sex: Males Animal Ref Microscopic & Macroscopic Findings sens KTeirlmliendalonSDaacyri:fic3e8 Animal i3 signed off from necropsy Gross Pathology Yo MAaLOcIRVrTEoARs,,copKBiRIADcINNEA,YbSn,SoPrImLNUaNAlGLiSt,CyORoMDEb,AsReErS,TvOeMdSAKCE:HL,ETADLUGMDUESNCNL,E, IBSSPULREGEMN,, NAIODLDREEE,N,ALSPAGALLNIACVNRADERSAY,S,GL`SACCNEIDCNSUF,MI,CMNACENORDLVOIENB,,ULAPRREICTTLUUIUMTM,APRYMNEOGSDELENA,TNEDTRiIvCriLnV.MH SFTFEEEHNANYURIRRYNO/IAIKNLDOGN/VEGLEELASARINJYCDONL,IKE,NSTP,,EAYRBUSA(TRTSEIH)RNYWARORWOMYII,TDBHLNGAOLODSAPDNETEDIRSC,, NETTRERVSAETC,EKSE,RS,KIENF.8D5IpPDiRWAOHGSUTASAR,TSE,, 661176 KATnieilrmlmaeildnal{o2nSaDaaicygrnief:dic3o8eff from necropsy Gross zathology --_ " No MLIAaILOcVERrEUToRANs,,,copKBPiRIAADcNINCNERA,YEbSAn,SoS,rPmLIUCNaNEAlGCLiSUt,MyC,ORHoDECb,AOsRLeTOSr,NTv,OeMdSARKCEEHCL,TEUTMAD,ULODMNEEUNSSUCEMLN,ET,EJRSISSCPULNELGEtMN,,t NATPHODHADRYREERY,IONAIXLDS/ALGGLALLRIAAIVNNOADDIR,SYY,, GPELA'YASRECNAI(DTASSIT),VIRCMWOIATNTNEDHRDVIGELBO,AUPNLTDAIPSRCI,TNLUETYIRRMTVAPAECRH,KYENROGS,DKLEIA,NED,a!sTpPVHRAOSGGU,RSN,E, SFEENUIRN/AKLNEVEESIJCOLEES,, USTREIRNNAURNY, BNLOADSDEER, TESTES, SiDIDWHDRS, EampanySaniized. oes vot containTSCA CS! --i ------------ Ed 28H--2D5a50y9S:tuRdeypienatMeadl-eDRoastesDermal Toxicity DuPont-11763 ~~ Dose Group:INDIIIIVI5DUmAaLsAksNIMASLexM:ICMRaOleSsCOPIC ANDMACROSCOPIC OBSERVATIONS Animal Ret Microscopic & Nacroscopic Findings se7177 TKAneiirlmmlaielndaloisnssDaaicygrnief:dic3o6eff from necropsy Gross Pathology No MALaOIcRVrTEoARs,,copKBRiIADcINNEA,YbSn,oSrPmLIUNaNAlGLiSt,CyORHODEb,AsReTrS,TvOeMdSAKCEHL,ETADLUODWEUNSUCML;E,'JSEPSLUENmUyN,, NAIODLDREEUE,MN,ALSPAGALLNIACVNRADERSAY,S,GLSACCNEIDCASUT,NI,CMNACENORLDVOIENB,,ULARPREICTKLUUYIMMT,PARHYMNEOGSDEAEN,DFE.RTTHVCHGLS,ub STPEHHMAYIRRNYOANILKD/LGVALERASYNINDCS,L,ES`,PBAYREUA(RTSIH)NYARWROYIITDHBLGAOLDAPDNTEDIRSC,, NETTRERVSAETC,EHSE,AS,KIENPE,SIODPPIHRDAOMGGIUIDSNE,TSE,, FEMUR/KNEE JOINT, STERNUM, NOSE se7178 TKoirlnliendalon sDaacyrif: ic3e0 Animal is signed off from necropsy Gross Pathology : ~ No MALaOIcRVrTEoARs,,coEKpIiRDcANNEA,YbSn.oSrPmILUNaNAlGLiSt,CyORHODEb,AsReTSr,PvOeMdSAKCE:HL,ETADLUODWEUNSUCML.E, JaSPyLtEnEiNn, NAIODLDREEUE,MN,ALSPAGALLNIACVNRADERSAY,S,GLSACCNIEDCASUT,MI,CMCNAOENLRDOVINEB,,ULARPREICTTULUIYMTM,APRHYMNEOGSDLEEAN,NTDE,RmIaCssLv.ibr SFTPEEHHMMAYIURRNRIOAN/ILKKD/NLEGVALEERASYNIJNDCOE,IL,NETS`,,PEAYRUESA(RTTSEIH)RNYNARUWROMIYI,TDHBLGNALOODAPSDNTEEDIRSC,, NETTRERVSAETC,EHSE,AS.KIENPB,ISDSIPPDRIIOAMSGITSDA,ETGE., --~ CompanySanltized.DoesnotcontainTSCA 2: Te R-- T -------- 282-5D5a0y9S:tuRdyeipn VealaeRtateDsedrm-alDTooxiscitey Dupont11763 ~ INDIVIDUAL ANIMAL MICROSCOPIC AND MACROSCOPIC OBSERVATIONS Dose Group 111 5 masks Sex: ales Sainal Rot Microscopic i Macroscopic Findings wn TTKeTirTmneiaanalo2n0SDaSaclyrnie+fai'c3oe8st trom necropsy Gxoss athlon Yo MaLvAcOkarNoEnonRse,.copRPBiiAacmNnuCnERA:vEmsAo,SSr,seTaONClNRGiGcStu)nyC,ORWODEbC,NsONLeTOSr,NTv.OeWdSARKGEE+HCL,TEUTMAD,LUOMWDUEESSNCHNLA,ET,ERJISECPLAELNEYNM,,PH SOSOERRETShGCLiiIaavNNRbDR,sY, GELSACRAIANATSRR,IICRYONOLENDRDVIGEBL,OANLDAPSRI,TLUTYIRWTAPACRHKYENROG,DLEA,EDS:OFPAHVAGSU.S, TFR ERARL ACTVSEASIJRCOLI,ENST,,BYRSRTTA)EARRWNYI,THBLNAOODSPDEEERC, NETREVSET,ES,SKIENF.IDPIRDOWSITDASTSE,, semen rRTeamiemnieandalo5n5sa2bceirydinfe+iac'36oese trom necropsy Gross satholosy --_ so MaKeAcCoerhveonnse,copBRPiaiancDctuiuEA:vnmems,oS,momTnCaiilomaicsto,Cy,onOWdbEC,AsoKreDorS,nvT,eOMdSARKCEEHCL,TSOTNDA,LIOWNUEDSSECRL,FEE,RJISCEPLTELE.NA,P SOSoOEnRiTaSShGCEiioaRbs,R, GSiSACRiIAoATSRA,IICRNONAIENDRDVIGELS,AUNLDAPSRI,TLUTIYRTNAAECRHYENAOG,DLEA,NEDS:OTPIHASGU,S. 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BE E unano msm,, eESsAaiD(h3oam)incsnoRylNiE,tRBVCLEOLA,PASESELBSREI,,RNGETITRToRVASAETRC.EYEsR.GS,KLIEANEDP.S.EoOrPiRDaOIcSDuTsAE.TSE,, EA ate: Sows, Seem. NOSE ~ gontainTSCA cai Company Sanitzed.Deo et e-- er ---- Bueee -- -- --r -- e 125-2Da5y 509:SRetpienautMelddDeoRsyesDermalToxicity Dupont11763 ~ INDIVIDUAL ANIMAL MICROSCOPIC AND MACROSCOPIC OBSERVATIONS Dose Group : 111 5 mak Sex: Males Satna Rat Wiroscopic & Nacroscople Findings ne SKTeeilramlaieinalo52nsDaSeciyrdinfe+iac3e8ote trom necropey Gross patholo o MSaiIcHmErEsoRRs.,,copaaRiinccDtiEAivnmego,S,romCiaCOlnNBisStE,yC,oORnbECyAsORLeTOrS,NvT,OeMdSAKRCECHLT,EOTNAD,LUNMDUESSECBL,NEF,EJREISSCPULNELGEaHNu,,b TSmTUOaARR,ORELLRDSACGGLAILIAAVRNNADRDR;SY,, GPLESAYCRABIAN(NTS6FH,)LYCRWWONAIIENTDRDHVIGELOB,APUNTLDIAPSCRI,TNLUEYITRMTRVPAAECRH,HYEOAGDS,KLEIA,NED.S:OTPPHRSAOGS,UTSA,TE, FSMTnNnLKaEVsESIJCoLnEeS,, USTREIRAIROHY,BLNAODSDEER, TESTES, EPIDIDIMIDSS, some RKToiimTmnTioanda)o5n0'sDaSaclyrnief+ai'c3o8ese som necropsy Gross patholo --_ No MSaSTcovErneRonaKs,,.copBKEiIRnDcAcNnDEAi,VbxSms,oS,rPmEICaNOlANBiLSCt,yC,ORORDbEC,AsORLeTOr,NSv,TeOdGNKRAEEC:CHL,TSOTRDA,ULOMWDUEESSYCBNLN,EF,ERJLSECPLTELE,NM,P SRNToAEeRA,ARTSLRS/AGCCLLIALAVRNDADYR,SY,, GILESAACYANIEADA(ISR)N,IRCOWNINIAEDTDRHIVGBELPU,ASLNIADPGSRI,TLUNEITYRRTNVAAEECR,KYENROGS,DLKEAI,RNBD,S,OTPPHIRAOYGSUT,SA.TE. FCEETRLREVESJIOCILNE,, USRTIEARARNY,BLNAODSDEER, TESTES, EFIDIDINIDSS. --_ scACEl riee-- e `C-- ompan-- y Sanii-- aed:Doe-- snotci ontaind T eer eemee Te 28H--2D5a5y09S:tRuedpyieantMeadl-eDRoasetsDermal Toxicity DuPont11763 --_ INDIVIDUAL ANIMALMICROSCOPICANDMACROSCOPIC OBSERVATIONS Dose Group 1 V 50 ng/kg Sex: Males Animal Ret Microscopic & Nacroscopic Findings Gores KTeirlmliendalonsDacaryif: ic2e8 Aninal is signed off from necropsy Gross seize ratholosy : No MaS`cOLrRiTvoAes,,copKBiIRcDANINEA,YbSm,oSrPmILaNUlNAGiLSt,yCOROHDbE,AsReTrS,vTeONdSAKCE:HL,ETADLUODMEUNSUCML,E, JESJPULNEGGMN,, AOID0DEREGE,NN,ALSAAGLCLIRAVNAEDRSSY,,GLSACCNEIDCASOT,MI,CMCNAOENLRDOVIENB,,ULAPRERICTTLUUYINMT,PARHYMENSOGDELEAN,NTDE,RTIHCUSLY.MPH TSDHERANRIOYNAADKL/LVGALERASYNINDCK,L,ESP.EAVREUA(RTSIH)NYARWROIIYTDHBLGALODAPDNTEDIRSC,, NETTRERVSAETC,EHSE,AS,KIENPE,SIODPIPHDRAVOGMSUITSDA,ETSE,, FEMUR/XNER JOINT, STERNGH, NOSE eKirlmliendalon sDacaryif: ic2e8 Snimal is signed off from necropsy Gross Pathology + No MaS`LcOirRvToeAsn,,copKBiRIADcIVNEA,VbSn,oSrPmILaNUlNAGiLSt,yCOROWDbE,AsReTrS,vTeONdSAKCE:HL,ETADLUODMEUNSUCML,E, JESJPULNEGSMN,, --~ ANTODODRREEN,N,ALSPAAGLNLICAVRNADERSAY,S,GLSACCNEIDCASUT,MI,CMNCAEONRLDVOIENB,,ULAPRREICTTLUUYIMMT,PARHYMNEOSGDELEAN,NTDE,RTIHCISL,iF RSHAERVOYIINDKA/LLAVGRLEYASININDCK,L,ESP,EAVREUA(RTSIH)NYARWROIIYTDHBLGALODAPDNTEDIRSC,, NETTRERVSAETC,EHSE,AS,KIENPB,SIODPIPHDRAYOGMSUITSDA,ETSE,, PEUR/KNEE JOINT, STERNUM, NOSE `CCoommppaannyyS5a2nitized.DoesntcontainTsCACE! -_-- 1.25509: Repeated-DoseDermalToxicity 28DsySudyinMaleRas Donley ~ INDIVIDUAL ANIMALMICROSCOPICANDMACROSCOPIC OBSERVATIONS Dose Group : V 50 ma/ka Sex: Males Animal ref Microscopic & Macroscopic Findings serie AKTneiirlmmlaielndal1osnSDasaciyrginfe:idc2e8off from necropsy Gross Pathotosy No MaALcOIRVzTEaARs,,copBKiRIADcINNEA,YbSn,oSrPmLIUNaNAlGLiSt,yCORHODEb,AsReTrS,vTOeNdSAKCEHL,ETADLUODMEUNSUCML,E,JESJPULNEUEMN,, JNTOOODBREUE,NH,ALSAPGLALINACVNRADERSAY,S,GLSACCNEIDCASUT,MI,CMANCNOEDLRIOVBNEU,,LARRPE.ICTTLUUYIMMT,PARHYWNEOGSDLEEAN,NTDE,RTIHCONULSY,Med TSPHEAYRRROIKAD/GLVLAEARSNYIDIC,KL,ESP,EAYREUA(RTSIH)NYARROWIYIDTHBGLLAOADPNDTDEISRC,, NETTRREVASECT,HEESA,S,KIENPS,SIODPIFHDRAIOGNSUITSAD.TEES,, FENOR/KNEE Jom, STERNUM, NOSE 667108 rKialmliednaonsDaacyrif: ic2e6 Animal $3 signed off from necropsy Gross Pathology POPLI`TDEIASLCOLLYOHRPAHTIONNO,DEDA+RK, RIGHT. --~ No MaALcOiRvrTeoAns,,copBKiRIADcINNEA,YbSn,oSrPmILaUNKlAGiLSt,yCORHODEb,AsReTrS,vTOeMdSAKCEHL,ETADLUODMEUNSUCML,E, JESSPULNEGEHN,, ANTODODREEE,,ALSAPGLALINACVNRADERSAY,S,GLSACCNBIDCASUT,MI,CMCANONELRDOVINEB,,ULARPREICTTLUUIMHT,APRYMNEOGSDELENA,TDE,RTIHCUSL,MP 667188 Continued on the next page PN `CompanySeitzsd.Doss no containTSCA CB! - 2F8-D25a5y09S:tRudyeinpMealaeRtateDsedrm-alDTooxisciety Dupont 11763 --_ INDIVIDUALANIMAL MICROSCOPICANDMACROSCOPIC OBSERVATIONS Dose Group : V 50 ma/kg Sex: Males Animal Rot Microscopie & Nacroscopic Findings Gries Convinued from previous page Gross Pathology Yo M"aFFcRrArYRoRYsONcTGoDKp/iGLcLAARNAYDAb,Kn,orFmEAaVRElA(iTStH)yYROIObITsDHeGrLOvAPeNTdDISC:, NETRRVAEC,HERS,KINE,SOPPHRAOGSUTSA,TE, SSEBUITNRAKLEVSESIJCOLIENST,, USRTIERNNAGRMY,BLNAODSDEER, TESTES, EPIDIDWMIDES, sees eAFnirilmmliaenlda)oinsDasaciyrginfe:idc2e3off fron necropsy Gross patholosy : No MaLEcovrKTaons,,copEBiIAocNLEA,VbSm,oSrPmLIUaNNlAGiLSc,yCORMODEb,AsNeTrS,vTeOMdSAKCEHL,ETADLUODYEUNSUCML,E,JSEPLNENEN,, ATToD0DR%%EN,N,ALSpKaGLnLIcAVaNADiRSaY,s,GLSACCNIBDNCSTU,LM,CINCOEODRLIVOBEYI,,LAPRREICTTUYUIANT,APRMYENSOGDELENA,TDE.RTIHCUSL,t REAATRRTOAATLD/CGVALERNSIIIIDCK,L,ESP,BAVREUA(RTSIH)NYARWROIIYTDHBLGALODAPDNTEDIRSC,, NETTRREVASECT,HEESA,S,KIENPB,SIODPIPHDRAIOGMSUITSDA,ETSE,, FEMOR/KNER JOIN, STERNGM, NOSE -- ~~ - `Eampany Saiz`DoesnotcontainTSCACBI se 281.2D5a5y0S9udReypeinatVeidl-eDRoastesDermal Toxicity Dupont11763 --_ INDIVIDUALANIMAL MICROSCOPIC ANDMACROSCOPIC OBSERVATIONS Dose Group : V 50 mg/kg Sex: tales Satnad rat oroseapie & Mackascopic Findings Fm Tr EieTlraaaior nsSsacyri+tic38ePp -- Gross satholosy Vo MaEvAcReronnohs:,copSBFiiRcDRruEEANbAsmS,os,ermThOaCaNlBsGiSCt,yC,oROWDbCA,sORLeDOrS,NvF.eOdSMRKMGGGCLHIEUTMDA,LUMMUEDSSCE,LVEI,EJRISECPLNELEEN,,H ORrPReEEaShCGLmITaNUsE,A.R, GaLSBAACYNRI3DNI(ST3)R,LCOWYLANiDNEmBRIVGBELoU,APLNRADiPRScI.,RNLOELTRRTMVAAECR,HYENAOGS,DkLEoA,kED,S,OTPPHIRUAOGSSUT,SA,TE. Bin kistJioisns", GSAEitRaNky, SLNAODSOEER, TRTES: EPIDIOMIDES. censs TTZooredmaiasnta)o2nsBWacanryiif+aioc3e8ee exam nacropey Gross Bathology --_ No MLeaTocOvnreEon:s,,copDSFiaiaaoActuciihA:vibean,soS,rPmIoCaNtlAusiLtt,yC,oROMDbCA,soRreTosS,nvh,OeMdSNRIGEA:HGL,IEOTNAD,LUOMWDIEESSNCEMLV,EG,ERJLBSTCPULNELGEHNP,,H TESeAaREimREAnYGECCGLaTiEvamDADiR,sY,. GBLBSAAUCSNBIAD(ATSSTI,)LICRMOWAININEDTDRVIGEBLO,UAPLNTDAIPSRCI,TNLOETYLARMTVAPASCRH,HYENAOSS,DKLEI,DNE,,STOPHNROGOSSUT,SA,TE. SFroLn sanVseSiJcotiis,. TSTREIRNN, BLOASDEDER, Testis. SPIDIDIVIDES. { `CompanySantas Dosnatconan TSCA C2 o------------EE-- R ------------ 2182-5D5a0y9:StRuedpyeiantMead-lDeoRseasDermal Tricky DuPont1763 --_ INDIVIDUALANIMAL MICROASNDMCACOROPSCIOPICC OBSERVATIONS Dose Group + v 50 my/kg Sex: ales Sana Ret Microveopia & Macroscopic Findings so RTTaeiernmeaidneo5n0spSaaciyrnia+fai'c7oe8te exon necropsy Goma pathology + No MLSaSocCviEreeonRHs,,copBEEiIiaDcaCuRnEAE,YbnSnS,oS,rpmLaCiilnBnisMt,yC,ORWODECb,AOsKLeTOrS,NvT,OeMdSARKCEE:HCL,TEUTMAD,LUOHMDUEESSYCEOLN,EF,EJRISICPLNLEN,i,F iNAToRmTOERiLnDLSECGGTiLAvaARAnNbDRY,SY,, GPLESAACRYNINBDNT(STA),IICRWNOAILNNTEDRDHVIGELSO,AUPYLTDAIPSRCI,TNLUETYIRRMTVAPAECRH,KYENROGS,DLKEAI,NIE,DS,OTPPHHRIAOGSSUT,SA,TE. FCEnLaeVRSJCoirzns,, SUToIHL, BLHAoDoDsER, TESTES, EPIDIDWNIDSS, ee) TRKoTimTniedndal5o5nsDaScairymicf+aic2e8oct trom necropsy Gross pathology, --~ No MaKvAcoearvonoense.,copPPBiiAacmCnEKnAvE.bsRa,So$,rPmTEoCaAvlBGLieNt)yC,OROWDbCE,sONLeTOrS,NvP.OeMdSARKCEE+HCL,REUTNAD,ULODNMEUERSSGCHHLNTE,E,RJISECPLAELNENP.,H TROSrIEEERiRRAOnRTshS/HCGGELLAAARRNNRDDRY,S,. GELESRACYNNIEWDASSIT),IRCONWIANIDYETDRHVIGELBO,AUPNLTDAIPSRCI,SNLUETYIRRHTVAPAECRR,WYENROGS,DKLEIA,NED,S.OTPPAHRDAOGSSUT,SA,TE. RCAnLraVsESIsCoLnies,, USRTINEANRY, BLRAODSDEER, TESTES, EPIDIDINIDES --_ CompanySanitzzeadd,: Donotscontsain nTSCACE! woe A -- 251.-2D5a50y9:SuRdeypeiantMeadl-eDRosaetDsermal Toxicity DuPont 11763 -- INDIVIDUALANIMAL MICROSCOPIC AND MACROSCOPIC OBSERVATIONS Dose Group + V 50 ma/kg Sex: Males Animal Ret Microscopic & Macroscopic Findings sea nKTeiirlnmlieandalo15nSDaicarynief:dic2e8off from necropsy Gross ratholosy No acKLezovonesenc,.opKDiIRcDANLNEA,YbSn,oSrPmILaNUlNAGiLSt,yCOROHDbE,AsReTrS,vTeOMdSAKCEHL,ETDAULODWEUNSUCML,S, JESJPULNEUEMN., MSIOOEFRRnE,LSPRAGLNLTCAVRNADERSAY,S,GLSACCNBIDCASUT,MI,CMCNAOENLRDOVIENB,,ULAPRRIETCLUNYINT,EARHYMNEOGSDLEEAN,NTDE.RTIHVCHULSA,GEH UCFHRAEROY,ILR/VGLLEAASRNIIDCN,LKE,SP,EAVREUA(RTSIA)NYARWROIIYTDHBLGALODAPDNTEDIRSC,, NETTRERVSAETC,EHSE,RS,KIENPE,SIODPIPADRAYOGHSUITSDA,ETSE,, FERRER JOINT, STERN, OSE -- --~ -_ jararn nt Company Saniized:Donoetcosn Ther ySanhized. Doesnotcontain TSCA CBI 2F-82-5D5a0y9:StRuedypienatMeadl-eDoRsaetDseal Toxicity DuPont 11763 ~~ INDIVIDUALANIMAL MICROSCOPIC ANDMACROSCOPICOBSERVATIONS Dose Group VII 500 ma/ky Sex: Males Animal Ret Microscopic & Macroscopic Findings Se1195 AKTenirilmmliaenldalo1nsSDasaciyrg:infeidc2e8oft from necropsy Gross patholosy Ho MALaOicRvrTeoAns,,copBKiRIADcINNEA,YbSn,oSrPmLIUaNNlAGiLSt,yCOROMDbE,AsReErS,vTeONdSAKCEHL,ETADLUODMEUNSUCML,E, 'JSEPTLNEUENN., NATOLDDEREUE,NN,ALSADGLALINACVNRADERSAY,S,GLSACCNEIDCNSUT,MI,CMNCAEONRLDOVINEB,,ULARPREICTTLUUYIMWT,PARRMYENSOGEDLEAN,NTDE.RTIHCUSLY,MPH BSTAERAMORINTADL GVLLAEARSNYIDRC,KL,ESP.EAYREUA(RTSIH)NYARWROIIYTDHBGLLAOADPNDTDEISRC,,NETTRERVSCETH,EESA,S,KISNPE,ISDOIPPHDRAWOGMSUITSDA,ETSE,. FEUR/KNEE JOINT, STERN, NOSE Histopathology LaverNIENCFRLOASWIMSA,SIOHNE,PNTOSCUEBALCLUUTLEA/RC,HROFNOICCA,L, FmOiCAnLi,malminimal. MEANyDI`BDUELGAERNELRIANTIPOHN,HOMDYEOPIBER, FOCAL, minimal PS PARATHNHYPRREORIOPDFLAGASLIAPANA,DISRLYPMRPEHSEONCTY.TE/PLASNACYTE, minisal 667195 Continued on the next page ... ~ Company Sanized, Dossnot containTSCACP) FTiN e 2H-82-5D5a0y9S:tuRdeypienatMeadl-eDoRsatesDermal Toriity DuPont-11763 ~~ INDIVIDUALANIMALMICROSCOPICANDMACROSCOPIC OBSERVATIONS Dose Group + VII 500 mg/kg Sex: Males Animal Ref Microscopic & Macroscopic Findings series Continued from previous page Histopathology : No M`iSXcPTrIOoNNsAEcLVoS,pCiORcLDU,NAGbSnS,oTrOMmSAaKClEHiL,tSyTADOLUbOsDMEeUNSrUCvNLe,Ed, JESJPULNEUEMN,, AIOLRETUAH,, BPRAANICNR.EAS, GGCEEECAAUNNMDD,S,, CTOTHLYHORUNO,SID,REGCLATADUNRMDE,,NAMLPEASGRELAANTNTHDEYSRR,IOCIDSLCGYILMAATPNIHDCSN,ONDEERT,VREA,CSHAEPLAII,TVUAIRTYARY E`PSPRSTOODSPITHDAAYTGHEUI,SD,RSSEB,MRIANRFAYELNNXUV/REL/SAKIRNCYELIEEXS,J,OIENYUTER,(ISN)ASRTWEYIRNBTULHMA,DODPETBRIO,CVENTEEMRSAVTREER,SO,W,SKINNO,SE, SKIN, TREATED, SKIN, UNTREATED 67196 TKeirlmliendalon sDacaryif: ic3e8 Animal is signed off from necropsy Gross vathology : No MA`aLOcIRrVToEAsR,,copBKiRIADcINNEA,YbSn,oSrPmILUNaNAlGLiSt,yCORHODEb,AsReTrS,vTOeMdSA:KCEHL,ETADLUODMEUNSUCML,E,JESJPULNEUEMN,, ~~ ANTDOLDREEE,N,A|LSRPGLALTNAVCNRADERSAY,S,GLSACCNEIDCASUT,NI,CMCANONELDROVINEB,,ULARPREICTTLUUIMPT,AHRYMNEOGSDLEEAN,NTDE.RTIHYCMULSY,MPH S`TPEHHMYATRRNOYAIALDX/VGLLEAASRNIYDCN,LK,ESP,EAYREUA(RTSIH)NYARROWIYIDTHBGLLAOADPNDTDEISRC,, NETTRERVSAETC,EHESR,S,KIENPB.SYODPIPHDRAVOGMSUITSDA.ETSE,, PEMOR/KNER JOINT, STERNUM, NOSE 67196 Continued on the next page - CompanySanltized. DossnotcontainTSCACBI --_Ti-- e -- 2H-82-5D5a0y9:StRuedpyeianteMdlDeosReatsDermal Toxicity Dupont 11763 ~ INDIVIDUAL ANIMAL MICROSCOPIC AND MACROSCOPIC OBSERVATIONS Dose Grow: VII 500 mg/kg Sex: Males Rainal Ref Microscopie i Macroscopic Findings serise Continued from previous page wiscopathology + wMaAvNeDsI,BIUNLPALRAGLTPIOHN,ODSEUBACUTE/CHRONIC, FOCAL, minimal. PANREYORNRVEOTHIORDFOCGAYLTAPONASDITSRS,PERREYSTEHNRTO.PHAGOCYTOSIS, minisal. Yo Mi`SKcACrDRoNsE,cvSo,pSiPcILNUNAAGLmSo,CrOmRWaDAl,RiEtS,yTOMSOAbKCsEHeL,rEvTeADdLUCNDUESVCML,E,JESCEULNEDEMN,, MTOLRETUAK,, PSSIAATLNUICTVRIAAARSRY,YGLGCABLNCADONSND,,, TCTOHMLROSON,I,DREGACLDTARONENDU,,KLMPGEALSRAEANNTDTHSEY,RRIOCISDCLIGNULTNAIFNCHDSNV.OEDREV,E, TEUYRRBAI(CN5HA)ERRY,WIBTLEAHSDODPOEEPRNI,GZUCST,ENSETRPEVASEA,,RIBSNKP/IXNLD,AIRDPIYRNIO,DSETSA,TE,PESUERM/IKNUNELEVEJSOIICNLTE,S, STERIM, BOVE MARROW, NOSE, SIV, TREKTED, SKIN, UNTREATED sonion ATKenirilmmliaenldaloinssDsaaicygrinte:idc3e8off from necropsy --- Gross pathology wosDILA+TATION, RIGHT, PELVIS, moderate. 667197 Continued on the next page .. PN - Company Sanitized.Does notcontain TSCAC' Tw 2H-82-5D5a0y9:SRuedpyeainteMdalDeosReatsDermal Toxicty DuPont-11763 --_ INDIVIDUAL ANIMAL MICROSCOPIC AND MACROSCOPIC OBSERVATIONS Dose Group : VII 500 a/kg Sex: Males Animal Ret Microscopic i Nacroscopic Findings Serie Continued from previous page Gross pathology + No M`aSLcPozivonEsRi,,copLCioUrNcdG,SA,bnWSoTEmORWaTAlC,iHt,ySDKOOEObLDsEETeNArULvNe,MdUSJCBLJEU,RUNS,PLEIRLN,E,AORPTAAN,CREBARSA,TN, ECSECaCIUNsMR,,ICCOMNLAEORNNVD,EI,BURLEPACITRTUUNLI,THAMRPEYSENGONLDATENE,DR,ICTHTYLHHYYUMRSPO,HIDANOGDDLREAE,NNDA,LSAGLLIAVNADRSY, REPYATERN(AA5T)RHYYWRIOBTILAHDDDGOELRPA,NCDST,ENSETRTEVRSEA,,CHEBSAPK,IND,IEDSYOPMPRIHODASEGTSUA,ST,E,FPESHNAEURNRYI/ANKXAN/LELEAVXEJISOIIINCN,TL,ES, rem, ose Histopathology KLIaDvNeEYISN;FLMOINTION, SUBACUTE/CHRONIC, FOCAL, minimal CDHIRLOANTIACT.IOPNR,OGPREELSVSIISV,E NUENPIHLRAOTPEARTAHLY,, mimlidn.imal. No MC`iLoconrndoc,ss.coSpTWiOEUcNAACA,Hb,noSrDKUmEGaLDlBEiTNtAUyLN,MOUbSsJCeELJrEUv,ReUdNS,P LETELNE,OH,AORPTNAC,REBARSA,TN,CBCSUPNI,NAL ~ CVNAEoNRrVDoEI,,BU"LBRAICRTTUOLLNYT,WAPRKYVSGNNOLTDAENE,DR,ITCHTYHNLYUYRSMO,PIHDAGNDOLRDAESNN,DA,LSGAPLLAAIRNVNDATSR,HYYRGOSLTCADINADTGSIL,ACNDS, UETVRREAD(CASHR)EAY,iBrLiEASDODOPEFRRFA,IGUCST,ENGETRBEVRSEA,,RVIBSKKP/IINLD,AIRDEYPNNRXIO,DSETSA.TE,FENSUERM/IKNNAELEVJEOSIINCTL,ES, STERIGM, BONE MARROW, ROSE, SKIN, TREATED, SKIN, UNTREATED ~ -_ {Eampaty Sanltized.DoesnotcontainTSCA CBI Tis 2H-62-5D5a0y9S:tRudeyipn eMaaleRtateDsedrm-alDTooxisciety DuPont-11763 ~ INDIVIDUALANIMALMICROSCOPIC ANDMACROSCOPICOBSERVATIONS Dose Group VII 500 mg/kg Sex: Males Animal ref Microscopic Macroscopic Findings Serio TFeirlmliendalon sDacaryif: ic2e8 Animal is signed off from necropsy ross ratholosy No MAa`OcIRVrTEoARs,,copBKiIRDcANNEA,VmSo,SmPaLIUlNNAiGLtS,yCOROMDEb,AsReErS,vTeOMdSA:KCEHL,ETADLUODMEUNSUCML,E, JESJPULNEURMN,, SNTOOODREEE,N,ALSAPGLALINACVNRADERSAY,S,GLSACCNEIDCASUT,MI,CMNCAEONRLDVOIENB,,ULAPRREICTTULUIYMNT,PAHRMYENSOGEDLEAN,NTDE,RTIHYCMULS,WP TSAEARMRIYONNADRL/LVGALERASYNIIDCK,L,ESP.EAYREUA(RTSIH)NYARRWOYIITDHBLGALODAPDNTEDIRSC,, NETTRERVSAETC,EHSE,AS,KIENPB,ISDOIPPDHRVAOMGSIUTDSAE,TSE,, SROR/KEE Jo, STERN, NoSE Histopathology KLaaveonIs;N;FLAMMATION, SUBACUTE/CHRONIC, FOCAL, minimal. "CHRONIC PROGRESSIVE NEPHROPATHY, minimal. --_ No Mi`CLcOiRrnDcos,s,coSpETiONcMRATCA.Hb,noSrDKUmEOaLDlEEiTNtAUyLM,MOUbSsJCeELrJEvU,eVdMS,P: LEIELNE,GH,AORPTAAN,CREBARSA,IN,CCSUPMI,NAL NSCEAoRRrVDiEI,,BU"LPRAIERTCUTIULMTY,AMRPYHWESGNIOLDANENT,DE,RLTCHTUHMYLURYSNO,PIHDADGRROLDAEENN,DA,LSGAPLLAAIRNVNDATSRH,YYROSGLLCADINADGTSLI,ACNDS, 667198 Continued on the next page -. --~ _-- Company Sanitized.Doesnotcontain TSCA CBI ise H-25509: RepDoseeDearmtalToexicdity 8DySwdyinMaleRas 0 Dwewlii ~~ INDIVIDUALANIMAL MICROSCOPIC AND MACROSCOPICOBSERVATIONS Dose Group VII 500 mg/kg Sex: Males nimal Ref Microscopic & Macroscopic Findings Geriss Continued from previous page Histopathology + No Mi"EcVTrER(Ao5Cs)EcRo,pWiIcTBHSOAPObAPnAToGIrUCmSa,lNiERtPVyHEA,ORbYIsSKeK/rILNv,AeRdYPAR:XO,STATE, SEMINAL VESICLES, RSTIENRANRUMY, BLBAODNDEERM,ARRTOEWS,TESO,SEE,PIDSIKDINY,NIDTERSE,ATEFDE,MURSK/IKNN,ESUJNOTIRNETA,TED 661199 TFeirlmliendalonsDaacryif+ ic28e nina) ia signed off from necropsy Gross pathology : No MA"aLOcIRrVToEAsR,,copBKiRIcADINNEA,YbSn,oSrPmILaUNlNAGiLSt,yCORONDbE,sAeRrS,vTeOMdSAKCE:KL,ETADLUOWDIESNCGLNE,,JESJPULNEUEMN,, OANODEDREME,N,ALSPAAGLNLICAVRNADERSAY.S,GLSACCNICDAUSTM,I,CMNCAEONRLDVOIENB,,ULARPREICTTLUUYIMMT,PAHRNYENSOGDELEAN,NFDE,RTIHCINULSY,MPH TFSHHERYIARNROYAIALDK/GVLLEAASRNIYDCI,KL,ESP,EAYREUA(RTSIH)NYARWROIIYTDHBLGALODAPDNTEDIRSC,, NETTRERVSAETC,EHSE,AS,KIBNEP,SIODPIPHDRAVOGMSUITSDA,ETSE,, FENUR/KNEE JOT, STERNUM, NOSE ~ Histopathology xvearoIsNF-LATION, SUBACUTE/CHRONIC, FOCAL, minimal. 667199 Continued onCHtRhOeNIneCxtP.RpOaGgReESSIVE NEPHROPATHY, minimal. ~~ Company Sanitized. Doesnotcontain TAA CF FL Ti -- 2H-62-5D5a0y9S:RteudpyeaitneMdalDeosReatsDermal Toxicity DuPont 11763 --~ INDIVIDUAL ANIMALMICROSCOPIC ANDMACROSCOPIC OBSERVATIONS Dose Group : VII 500 mg/kg Sex: Males Animal Ref Microscopic & Macroscopic Findings Series Continued from previous page Histopathology + IPOANRDAITBEHURYLRYAOTRIHDRLOGYCLMYAPTWHODSSNIOSD/+EERVTAROPAGOCYTOSIS, mild. ERTDIiDNMFNLIADODEFASTAI+ POANI,R PRESENT. SUBACUTE/CHRONIC, FOAL, minimal No WiC`Lcoirnndoa,ss,coSpHTiEONcMRAYCA,Hb,noSrDKUmECaLDlEEiTNtAUyLM,MOUbSsJCeELJrEUv,NeUdMS,P:LETELNE,CH,AORPTAAN,CREBARSA,IN,CECSUPMI,NAL DoTYtSRoO,,TD"GARLDEARCNETDN,,ALWPGEALSRAEANNTDTHSEY,RREOCISDCLIGNPLTAIHNCDSNN,OEDREVT,ER,ACSHAPELIAIT,VUAIRTEAYSROYPGLEAAGNGLDUASSN,.D, S"FHEEAMURIRYN/NAKGLN/LGVAEERSYIJNCOGLI,ENSTE.,VEUS(RTSIE)RNNAURWMYI,THBLBAOODPNDTEEIRCM,ARNRETOREWVS,ET,ESN.OSSKEI,N, PROSTATE, SKIN, TRENTED, SKIN, UNTREATED 667200 Kseirlmlienda)onsDaacyri+fic38e Sninal {s signed oft from necropsy --~ Gross vatholosy : xaoDsILATATION, PELVIS, RIGHT, moderate 667200 Continued on the next page - CompanySanitized.DoesnotcontainTSCA CE. Ties: 2H-82D5a50y9:StRuedpyeiantMeda-lDeoRsaetDsermal Toxicity DuPont 11763 ~~ INDIVIDUAL ANIMAL MICROSCOPICANDMACROSCOPICOBSERVATIONS Dose Group : VII 500 mg/kg Sex: Males Animal Ref Microscopic & Macroscopic Findings 61200 Continued fron previous page Gross pacholosy : No MaSScPvrIeoinsA,cLopC"LioincNdG,AS,bnHSoTrEOsNWaASlC,Hi,tySKDOEUbLCsEDTeEArNLvHe,MdUSJ:CELJEU,NUMS,PLIELEENQH,AORPTAAN,CREBARSA,IN, GCSiCoIaiNunTs;I,CCONWLEAORNNVD,EI,BURLEPCAITRTOUMLI,TiAMRnEYSENGONLDTAEED,R,ICTHTYHLNYYURMSPO,HIDANOGDDLREAE,NNDA.LSAGLLIAVNADRSY, CEPRVAEER(NNSAT)RIYRWOIBITLDAHDDOGELPRAT,NIDCST,ENSETRTEVRSEA,,CHEESRKP,IIND,IEDSYOPNPRIHODASEGTSUA,ST,E,FPESRMAEURMRYI/INKKAN/LELEAVREJNSONIIKNC,TL,ES, vem, HOSE Histopathology : KLaivoenrEYIsNF+LATION, SUBACUTE/CHRONIC, FOCAL, minimal. HONDIDBCIHULRLAOATNRAITCLIYOPHNPR,HOGNRPOEELDSVSEIISV,E NUENPIRLRAOTBEARTAHLY,,mimlidn.imal SARATYIPVERORLPDLAGSLIAAN,DSLY MPHOCYTE/ELASACYTE, minimal. `ONE OF A PAIR PRESENT. ~ No MiC`Lcoornwdoc,sS,coSpWTiEOAcNRATCA.Hb,noSrDKUmEOaLDlEEiTNtAUyLY,WOObSsJCeELrDEvU,NeUdMS,P:LEISLNE,UM,AORPTAAN,CREBARSA,IN,CECSUPMI,NAL VAotRSoO,T,D"RGAELGCARTNEODNN,,ALNSGBALSRAEANNTDTHSEY,KAEOCISDCLIGYALMTAPINHCDSNN,OEDREVT,ER,ACSHPAEILAIT,VUAIRETYSAORPGYHLAAGGNLUDASSN,,D, 667200 Continued on the next page ... ~ - CompanySanltized.Dossnotcontain TSCA CBI Ti: 21.82D5a50y9:SuRdeypeisntMda-lDeosRaetDsermal Toxicity DuPont. 11763 -- INDIVIDUALANIMAL MICROSCOPICANDMACROSCOPIC OBSERVATIONS Dose Group : VII 500 ng/kg Sex: Males Sinal Rot Microscopic & Macroscopic Findings Ser200 Continued from previous pase Hiatopathotony No MiErcErMoTRsNcAoLpiVLcRASIARCbLn,EoSr,mBaYlEU(iRStI)yNAROWYIbTsHeBrLvAODePDdTEIRC,NETREVSET,ES,SKIENP,DIPDRIONSITDAETSE,, SFKIEN,RKTuREEASTEJD0,iNES,KINS,TERONNUTMR,ENTBEODN.E NARROW, NOSE, ser200 TKeirlmliendalonsDacaryi:fic2e8 Animal 5s signed off from necropsy Gross satholooy : LPaOvPeLnIoTEcAtL, LoPwR,OFDEEM. + `TaRGe, DARK. No MSaEcRoArwToeNsr,cso,pSiPcTIONANAGbLSn,oCrOmRHDaE,lARiTt,ySTOSOWKbAEsCLeH:ErTvAeDULdGDWEUNSTCMLNE,,JESJPULNEGEMN,, ATOLRETUAN,, --_ GEALNRALCNTHDUESAR,RSY|,SGCLCIRAACNTUDIMSC,, NEMCROAVLNEOD,NI,BUDRLIBATCRUTTULEMYA,VRFYHNGELNSAOENDNDET,,ERITTCHHOYHRLUOPSI,DHGALNDAORNDEDEN,,AL SARATRIRORD GLANDS, TRACHEA, ESOPHAGUS, PHARVIK/LARINK, RSEYTaEA(nASuR)Y,WBoLNTAoDsDeOEPRT,ICTENSETREVSE,, SSKPIIND,IDYPHRIODSETSA,TE,FENSUERMI/NKAVLESVEJSOIICNLTE,S, 667201 Continued on the next page... --~ --_-- Company Sanitized.DoesnotcontainTSCA CBI ion 21.52D5a50y9S:udRy ienMlpDeoResaetDsaertaTeicd Duron 11768 --- INDIVIDUAL ANIMALMICROSCOPIC ANDMACROSCOPIC OBSERVATIONS pose Group VEE 500 nafs sex: tales Tail Rat Microscopic i vacoscapie Findings Genon Continua fron previous page iecopatholony avnE ra iscors onic, Foca, minsnal. p foobcarEy RNeTrIoOsN, WBrOTRRTOA,GGFEOICATLO,SImSi,nims.inis rorLRe eRE EitnWe Vberocimse prasacins, mia vo MiecromscopCicfOonnmCoe"rrRomSouaetclbohi,.EtIyAHDLEOSibPsFoNeOTrGpEvRL,eLEdC,,J L`EsoiNumbNer,,NODoIEL,RE,S,ALBITROAANAICRNRY,ERS, ewnsAsmhaSonsoL,AusPA,GALIANIEDYRSBG,(T5)DSCWCLNLETATISCSO,NPETRLTVCAEC,NHEERPAVX:ET,UITSKAIRNY, o Fie re e,SSIOhNA ,FASTwSr,saJAOTIEND. STEN BONE HARRGH, HOSE, --~ CompanySanitized.Doss FlGonainTSCACBI ee----or r-- e-- e -- ---- -- H2.82-5D5a0y9S:tRuedpyeiantMeadl-eDoRseasDermal Toxicity DuPont-11763 ~ INDIVIDUAL ANIMAL MICROSCOPIC AND MACROSCOPIC OBSERVATIONS Dose Group : VII 500 my/ka Sex: Males Ininal Ref Microscopic & Macroscopic Findings Ger202 AK`TnieilrmlmaeildnaloinsssDaaicygrinfe: idc2eo8ff from necropsy Gross patholosy Yo MA`aLcOTrRVoETsRA,copBKiRIADcINNEA,YbSn,oSrPmLIaONNlAGiLSt,yCOROWDEb,AsReTrS,vTOeWdSAKCEHL,ETADLUODMEUNSUCML,E, JSEPILUENEONN, AoTDoRREHE,N,A|LSAPGLALINACVNRADERSAY,S,GLSACCNIRDNCSTU,IM,CMCANONELRDOVINEB,,ULARPREICTFLUUYINWT,PAHRNYENSOGDELEAN,NTDE,RTIHCOSLY,MPH S`TPEHANYARTRONYIAADLR/GVLLEAASRNIYDCN,LK,ESP.BAYRBUA(RTSIH)NYARROWIYIDTBHGLLAOADPNDTDEISRC,, NETTRERVSAETC,EHSE,AS,KISNEP,SIODPIPHDRAVOGMSUITSDA,ETSE,, FEMOR/KNEE JOINT, STERN, NOSE Histopathology : LavemIN+PLAYMNTION, SUBACUTE/CHRONIC, FOCAL, minimal. MLUeDsIBHIELMAORRRHLAGHER, ANLOVDEEOLAR, FOCAL, minimal. HPERPLAGTA, LYHPHOCYTE/PLASACYTE, mininal --~ 667202 Continued on the next page CompanySanfized. Doonotcontain TSCACE! Tie A -------- H.25509:RepeateDedrm-aDlToosisciety 28DaySudyinMeleRas Dowie --~ INDIVIDUALANIMALMICROSCOPIC ANDMACROSCOPIC OBSERVATIONS Dose Group : VII 500 ma/kg Sex: Males Ininal Ref Microscopic & Nacroscopic Findings Ser202 Continued fron previous page Histopathology Yo MiS`KcPirooRNsELcvoS,pCiORcHDE,AAbRnS,oTOrMmSAaKClEHiL,tETyADLUOObDMsEUeNSrUCvNLe,Ed, JESJPULNEUEMN,, AIOLRETGAH,, BPRAANICNR.EAS, GGCIIEAnNCNDD,,S, TCTHoHYoYRlMO,IISD,REGCLATADUNRMDE,,NALMPEAGSRLRNAYTNTHDEYSRR,IOCIDSCLGIYLANATPNIHDCSN,ONDEERT,VREA,CSHAELPAII,VTAURIYTARY EPSRSPOOISPDTRIAADTGIEUN,SI,DESSPH,HIANRFAVEILUGRKV//ELKSANIRCEYLENEKS,J,OIENYUTER,(ISN)ASRTEYWRINTBUHLMA,DODPETBRIO,CNENTEEMRSAVTREEK,SO,,SKINNO,SE, SKIN, TRENTED, SKIN, UNTREATED 667203 mKeirlmliendalonsDaacyri:fic28e Animal is signed off from necropsy ross Pathology + No MaJLcoirRvTeoans,,copKBiIRcDAINNEA,YbSn,oSrPmILaNUlNAGiLSt,yCORWODbE,sAeRrS,vTOeMdSAKCE:HL,ETADLUODMEUNSUCNL,E,SSEPCLOESNN,, --~ AOSDDEREME,N,ALSPAAGLNLICAVRNADERSAY,S,GLSACCNBIDCNSUT,MI,CMCANONELDROVINEB,,ULARPREICTTLUUYIMKT,PARHYMNEOGSDELENA,TDE.RTIHCOWLSu,te S`THEHANVRIRYNONAIRLD/LVGALERASYNINDCK,L,ESP.EAVREAU(TRSHI)YNRAORWIYIDTHBGLLAOADPNDTDEISRC,, NETTRREVASECT,HEESA,S,KIENBP,SDOIPPDHRAAOGISUTDSAE.TSE,, PENUR/KNER JOINT, STERNUH, NOSE 667202 Continued on the next page... ~~ - CompanySaniized.Doesnotcontain TSCACBI Tio: F2-62-5D5a0y9S:tRudey ipn MealaetRaetDsedrm-alDTooxisciety DuPont 11763 ~ INDIVIDUALANIMALMICROSCOPICANDMACROSCOPIC OBSERVATIONS Dose Group: VIT 500 mg/kg Sex: Males Animal Ret Microscopic & Macroscopic Findings 567203 Continued from previous page Histopathology LIVERIN: FLAMMATION, SUBACUTE/CHRONIC, FOCAL, minimal. KMIEDSNEENYCTSHERROINCICLyMPpRsOGNROEDSSEIV:E NEPHROPATHY, minimal. MANDIEBERURYLYTATARARROOLCCYYYNTTPOOiSST1SNS)O/DEEERRYV:TTHHRROOPPHHAAGGOOCCYYTTOOSSITSS,, minimal. minisal PARATHFVYPREORIPDLAGSLIAAN,DSLY: MPHOCYTE/PLASACYTE, minimal. ONE OF A PAIR PRESENT. No MCi`OLciRrNDoG,sS,coSpTWiOEMcRATCA,Hb,noSrDKUmEOaLDlEEiTNtAUyLL,MOUbSsJCeELrJEUv,NeUdNS,P:LEIELNE,UM,AORPTAAN,CREBARSA,IN,CECSUPMI,NAL CSOCtIoAwT,iC"RNEECRTVUEM,, SBAILTIUVIATRAYRYGLGALNADNSD,, TTHIYNRUOSI,D GALDARNEDN,ALPGALRAANTDHSY,ROID EGUVLREAI(NNSDA)SR,YWITBTRLAHACDHDOEEPART,,ICTEESNSOETRPEVHSEA,,GUSSE,KPIINDP,IHDAYRPMYRINODKSE/TSLA,ATREY,FNEKSM,EUMRT/NKANLEEVEJSODINCTL,ES, STERN, BONE MARROW, NOSE, SKIN, TRENTED, SKIN, UNTREATED --~ --~ - CompanySeized. Doss otconlain TSCA CB! Ties 2F6-2D5a5y09S:tuRdeypienatMeadl-eDoRsaetsDermal Toxicity DuPont-11763 ~~ INDIVIDUAL ANIMALMICROSCOPICANDMACROSCOPIC OBSERVATIONS Dose Group : VII 500 mg/kg Sex: Males Animal Ret Microscopic & Nacroscopic Findings se7208 TKeirlmliendalonSDaacyrif: ic28e Animal is signed off from necropsy Gross Pathology : No MaA`LcOERrVToEAsR,,coKpBIiRDAcNINEA,YbSn,oSrPmILaUNlNAGiLSt,yCORHODEb,AsReTrS,vTOeMdSAKCE:HL,ETADLUODMEUNSUCNL,E,JESJPGLNEEUNK,, ANTODUDRREED,N,ALSPAAGLNLICAVRNADERSAY,S,GLSACCNEIDCASUT,MI,CMNCAEONRLDVOIENB,,ULARPREICTEULUINMT,APRYMNEOGSDLEEAN,NTDE,RTIHICNULSY,MPH STPEHRMAYIRRNVOAIILOD,H/VGCLEAASRNIYDCN,KL,ESP,EAVREUA(RTSIH)NYARWROIYITDHBLGLOAADPNDTDEISRC,, NETTRERVSAETC,EHSE,RS,KIENPE,SIODPIPHDRAVOGMSUITSDA.ETSE,, 'PEMUR/KNEE JOT, STERNUN, NOSE Histopathology : HvEeARnTINFLATION, SUBACUTE/CHRONIC, FOCAL, minimal. Reco"D:EGENERATION, MYOFIBER, FOCAL, minimal --_ MANDIEBMRiUYsLTsAHiRRvGeLC.YYMTEOHS1NSO/DEERYTHROPHAGOCYTOSTS, mild. PARATHOYNREOIODF GALAPNADISR. PRESENT. 667204 Continued on the next page ... ~~ CompanySanitized.Dossnotcontain TSCACBI J ise 251-.2D5a50y9:SuRdyeinpMealseRtateDsedrm-alDTroicsitey Dupont11763 --~ INDIVIDUALANTAL MICROSCOPICANDMACROSCOPIC OBSERVATIONS . Dose Group : VIE 500 masks Sex: ales Aainal Ref Nicroscopie & Macroscopic Findings senza Continued from previous page nistopatholony : Yo MiESScoPErwiEobns,iLcso,pGCiooRcStbOo,NA,GbSnS,oMhrEmSoSaEKwlNEiT,LtEEyRTID,CUOObDNsLUEeYSNrMCCvPLHeHE,d,NOJ:DESEJP,ULNEUESMNA,,LIAVIOALRRETYUA,,GLBPARAASNDC.YR,EAS, rT`ARsROC,TARAGILDNARNEEDN,,AL`GPELAVAREAN(TDSHS)Y,RWOISITCDHIGNLFOAIPNCTDISNC,ERNVETERR,VAEC,HPEIATS,UKIINTE,ASROYPFHRAGOGLSUATSNA,DT,E, SFSEKiT,nuASLTERVEEEASTIEJCDOL,IENSTS,,KINUS,RTIENORANRTNRY,IABTLBEAODDNDEERW,ARRTOEHS,TESR,OSEE.PIDIDWMIDES, cramnsecwroor Bx: ~~ --~ - CompanySanilized.DossnotcontainTSCACE! oe: