Document 2jgKj1aqqwDp62zoe6raoKL86

AR R26 33S 497 ---- --_ AR226 3315 suptenents bony TRADE SECRET Study Tide 90-Day Gavage Study iHn2R5at4s25wi:thSOunbec-hGreonneircaTtoixoinciRteyproduction Evaluations Supplement 1 Laboratory Project ID: DuPont-11418 TesT GUIDELINES: OUSP.PTESPA87H0e.a3l1t0h0E(fAfUecGt-s1T9e9s8t)Guidelines -- AumOR: Susan A. MacKenzie, V.MD., PhD. D.ABT. STUDY COMPLETED ON: August 1, 2003 SUPPLEMEN1T COMPLETED ON: March 19, 2004 PERFORMING LABORATORY: HEaLskdelulPLoanbtodreatNoerymofuorrHseaanldthCaonmdpEannvyironmental Sciences NElekwtaornk,RoDaedl,awP.a0r.e B1o9x71540-0050 work Reauesruex {JAY . SERVICE Cope NuMBER] . . --_ Pegs Tor97 -- CompanySanitzed. Doss not contain TSOA Gol 5205-4D2s5y:GovSsugbcehSrtoundiyciTnorRiactistywith One-Genersion Reproduction Evaluations DSuuppopnlte1me1n4t18 --~ GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT L"TahbiosrsautpoprlyePmreancttiwceasStcaonnddaurcdst,edwhinicchomaprleicaonncseiswtietnht wUi.tSh. tEhPeAOETCSDCAPr(i4n0ciCpFleRs opafrGto7o92d) Good GLaoboodraLtaobroyraPrtaocrtyicPera(catsicreevSitsaenddianrd1s99(75)9pNuobhlSisahnedNuinmEbeNrV/3M85C0/)C.HEM(98)17 and MAFF Japan Appli/Scpoansnort: E.L du Pontde Nemours and Company Wilmington, Delaware 19898 USA. StudyDirector:__Susan 0Mmae[IN Susan A MacKenzie, V M.D, PRD. DAB. Senior Research Toxicologist 19- MADaRt:e 2008) ~ Applicant / Sponsor: "DuPont Representative Date -- rere Company Sanitized. Does not contain TSCA CBI B502-8D4a2y5;GaSguebsSonaiyc iTnoxRiacistyitOn Gerson Reproducion Elion DSuubppaliement QUALITY ASSURANCE STATEMENT Haskell Sample Number(s): 25425 Datesof Inspections: Supplement No. 1: March 1-2, 2004 Dates Findings Reported to: `Study Director: March 5, 2004 Management: March 5, 2004 ~ Reported by: Pulm fT Staff Quality Assurance Auditor 19-March-B004 Date Pe. ------ Company Saritized. Doss not contain TSCA GBI 9B02.5D4a2y5:GavSaugbesSotnuidcy iTnoxRitcsityvithOneGeneration Reproducion Evausions DSuupppleome1n1t4181 --_ CERTIFICATION fWreo,mtthheisunsdteudrys.igned, declare tha tis report provides an accurate evaluation of dta obtained Approved by: 9 4 Loy Scott MB.anLaovgeelmeessn,tPhD. |S MAR Zoet Date IssuedbyStudyDirector: SSuusasnaAn. nMaQcKeMnzaie,cVKMeDw.riPshD. DABT. 19- MDAatRe 2004 `Senior Research Toxicologist --~ --_ S--r --------------------e Company Sanitized. Dnootconstain TSGA GBI 0H2-5D4a2y5:GavSaugbcehSrtoundiyc iTnoxRiactistywithOneGeneration Reproduction Evaluations --_ DSuuppopl-e1m1e4nt181 TABLE OF CONTENTS Page GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT cov QUALITY ASSURANCE STATEMENT worms CERTIFICATION corrssmsssmsssmmssmsmssmmsmsmsmssmosssmssssssrsnosd STUDY INFORMATION corns REASON FOR SUPPLEMENT L.ccnrmssnmssmssmsmmsmmsmsssmsmsssssssnnsod] SUMMARY c.carranmmssssmmmsmmsmmmsmmssomomimmso LIST OF TABLES `TABLE 1 PLASMA PFOA CONCENTRATIONS... `TABLE 2 SUMMARY OF BLOOD TOTAL FLUORINE ANALYSIS... ssn I ~~ LIST OF APPENDICES APPENDIX AANALYTICALREPORT sss APPENDIX B INDIVIDUAL ANIMAL BLOOD FLUORINE... SY S-- --~ 3 Company Sanitized. Dos not contain TSCA CBI 2F50E0D-aDayyOGeaargageeSS-- ynin RRaats wvithOOnneeGGevnerasttiionReprodcion EBvailuuaiioons 9th Collective mm STUDY INFORMATION Symonyms/Codes' + H-25425 HaskellNomber: 25425 CAS Registry Nome: GN eu} DSuuuppreleimienengt1 1 KaounImpure --| Phusical Characteristics: Amber-ellow-brown solid Stability: Tofhethetessttusduyb;stnaonceeviadpepnecaeorefdintsotabbeilstiatbylewausndoebrsetrhveecdo.nditions Sponsor: E.L du Pontde Nemours and Company Wilmington, Delaware 19898 USA. Study Initsted/Completed: October 3, 2002 (see report cover page) . In-Life Initiated/Completed: October 15,2/0Ap0ri2l 15, 2003 Company Sante. Does ot contain TSCA GBI H902-5D4a2y5:GavSaugbeehSrtouidcy TinoxRiactistywithOneGeneration Reproduction Evaluations DSuuPpopnlte1me1n4t18| --~ REASON FOR SUPPLEMENT 1 As described in protocol amendments 1,6, 8, and 9, the sponsor requested analysis of plasma samples collected at the time of necropsy for concentrationofperfluorooctanoic acid (PFOA), and analysis of selected whole blood samples, collected prior to and during the dosing phase of the study, for total fluorine. `This supplement contains the resultsofthe analyses which were conducted by Emily R. Decker of Exygen Research, State College, PA (PFOA concentration) under the supervision of John M. Flaherty,andWard R. Gibson of Jackson Laboratory, Deepwater, NJ (total fluorine concentration), under the supervision of Robert M. Good. -- --_ ee `Company Sanitized. Does not contain TSCA CBI 9H02-5D4a2y5:GavSaugbechSotnuidcy iTnoxRiactistywith OneGeneration Reproduction Evaluations --_ SUMMARY DuSPuoppnltem1e1n4t181 HFo-u2r54g2r5ouipns0o.f0y5o%umnegthadyullctelmlaulleosaenidnfdeemiaolneizCerdlw:aCtDer(bSyD)gIaGvSagBeRforratasppwreorxeimaadtmeilnyis9t0erdeadys. (92 days in males and 93 days in females), at dosages of 0, 10, 100, or 1000 mg/kg/day. Selected animals from each dosage group were designated for evaluations of subchronic toxicity, recovery from subchronic toxicity, or reproductive toxicity. Under the conditions of this study, the NOEL. for subchronic toxicity endpoints was 100 mg/kg/day in male and female rats, based on reversible, minimal to mild thyroid follicular hypertrophy, observed in the 1000 mg/kg/day groups. Under the conditions of this study, the NOEL for reproductive endpoints was 1000 mg/kg/day, based on a lackofeffects on anyreproductive endpoint in Py or Fy generation animals exposed to the highest dosage tested. Blood was collected at necropsy, at the end of dosing and after a one-month recovery period (control and high-dose rats only), for analysis of perfluorooctanoic acid (PFOA). PFOA was extracted from plasma by protein precipitation in acetonitrile. The compoundwas quantified by liquidchromatography andem mass spectrometry (LC/MS/MS) analysis using selected reaction `monitoring (SRM). Quantification was performed using extracted calibration standards containing an intemal standard. The lower limit of quantitation (LLOQ) for this method is 10 ppb. ~~ Blood was collected at selected oftotal fluorine. Samples were tainmaelpyoziendtsfrtohmromuaglheosutatnhdefdeomsailnegs pihnaaslle doofstehegrsotuupdsy ofonr taensatlysis day 22, from high-dose males and females on test day 89, and from high-dose males on test days 4 (pretest), 3, and 9. Whole blood was analyzed for total fluorine by the Wickbold torch `combustion method and an ion selective electrode. The limit of detection for the method is 0.5 ppm. Results of both of these analyses are presented in this supplemental report. "The resultsofthe PFOA and total fluorine analyses are summarized in Tables 1 and 2, respectively. The details of the analysesofPFOA, which were conductbeyd Exygen Research, arereporteidn Appendix A. Individual animal total fluorinedataarereported in Appendix B. PFOA concentrations, measured at the end of the dosing period, were below the LLOQ in ll control males and in ll females dosed with up to 100 mg/kg/day. At the endofthe dosing period, the mean concentration in male rats was 51.7 ppb in the 10 mg/kg/day group, 147 ppb in the 100 mg/kg/day group, and 3621 ppb in the 1000 mg/kg/day group. After a one-month recovery period, the mean concentration in the 1000 mg/kg/day male group was 400 ppb. Females dosed with 1000 mg/kg/day hadamean concentrationof 51.7 ppb at the endofdosing. All females in this dose group had concentrations below the LLOQ at theendof the recovery period. Concentrations in control males and females were below the LLOQ at the end of the: recovery period. -_-- `Company Saniized. Does not contain TSCA CB H902.5D4a2y5:GavSaugbechSrtoundcy iTnoxRiactistywithOneGeneration Reproduction Evaluations DSuuPppolnetme1n1t4181 -- Low, but measurable, levels of total fluorine were present in blood from all but one control males and all control females on test day 22. Mean values were 1.18 ppm in males and 1.38 ppm in females. A dose-related increase in concentration was observed in both sexes on test day 22. Male mean values were 1.31 ppm in 10 mg/kg/day males, 1.8 ppm in 100 mg/kg/day males, and 4.74 ppm in 1000 mg/kg/day males. Mean female values were1.54ppm in 10 mg/kg/day females, 1.91 in 100 mg/kg/day females, and 3.32 ppm in 1000 mg/kg/day females. In male rats dosed with 1000 mg/kg/day, concentrations were below the limit of detection for all rats prior to dosing, but demonstrated increasing concentrations over time, with no plateau evident near the. end of the dosing period (test day 89). In femaleratsdosed with 1000 mg/kg/day, total fluorine levels did not change from test day 22 to 89, and blood concentrations were lower than in males on both test days. --~ --- `Company Sanitized. Does not contain TSCA CBI 9205.0D2a5yG:avSaugbechSvtouidyciTnoRxaitcistwyithOneGeneration Reproduction Evaluations -- TABLE| Supplemen1t Dupon11418 PLASMA PFOA CONCENTRATIONS DESIGN [MEASURED CONCENTRATION pb) DOSAGE FEMALE (mg/kg/day) [MEANSD._n|MEAN SD. n Endof Exposure* 0 10 100 1000 <100 0 10/<100 0 10 517 194 10[<100 0 10 14717210 <100 0 10 3621 846 10] 517 25.110 Endof 1-MonthRecovery' 0 <100* 0 10[<100* 0 10 1000 400 305 10/<100* 0 10 n+A=llnvuasmobfbsaeemptllhreesloowwer imi of quantitation (10.0ppb). --~ SDt.est=dsatyan9d2ar(dmdeavilaoetirso9n)3 (females) b test day 126 (maandlfeemalses) _ - `Company Sanitzed. Doesnotcontain TSCA CBI 0B-25D4a2y5G:avSaugbeehSvotnaiyc iTnoxRiactistywith One-Generaion Reproduction Evaluations ~~ TABLE 2 DSuuPpopnltem1e1n4t181 SUMMARY OF BLOOD TOTAL FLUORINE ANALYSIS BLOOD FLUORINE (ppm) Growp1/I DAYSONTEST __ Omghkg/day GroupII/IV 10 mg/kg/day Group V/VI GroupVII/VI 100 mg/kg/day 1000 mg/kg/day MALES "+ v <0.50" 005) 3 M > * 165 0.16(5) 9 3.59 0.26(5) 2 118 131 1.86 474 0.44(5) 036(5) 03165) 0.45(5) rm 8 FEMALES 2 > v > 9.86 0.66(5) 138 154 191 332 04065) 02265) 03965) 0345) 89 > > pb 330 0.62(5 Data arranged as: SMteaanndard deviation (Numberofvalues included in calculation) ~ >3 SaWmhpelreesinndoitviedvuaalluavtaeldufe rvatshi<s0t.i5,me0p.o5inwta.s used to calculat2e the mean and standard deviation. *_ All values below the limitofdetection 0.50 ppm). --~ --- Company Sanitized. Does notcontain TSCA CB 012-5D4a2y5:GavSaugbcehSvtourdiyc iTnorRiactistywith One-Generation Reproduction Evaluations Supplement 1 DuPont 11418 PS APPENDIX A ANALYTICAL REPORT --~ -_-- `Company Sanitized.Doesnotcontain TSCA CBI 209H-20D5Da4a2yy5a:GvavaSauggboehSrStotunudidyyciTinnoRrRaiatctsistwywiitthhOOnnee-GGeneenreartaiioonnRReepprrooddvuecttiioonnBEavalluuaattiioonnss_________DDuuSPPuoponpwlte11m1e14n4t1183| --~ STUDYTITLE 90-DayGavagsSudy i2n 5Ra4t2s5wi:thSOonbee-hGreoaneircaTtoixoinclRteyprodoetion Evaluations "RDAETQAUIREMENTS AnalyticalMethodRequirements STUDYDIRECTOR Susan A. MacKenzie ANALPHYASETCOIMPCLETAEDOLN November 19,2003 'EERFORMING LABORATORY / TESTING FACILITY ~ 30E5x8yRpeesneRaerscehaDrrcihve `SPtheoCneo:l8e1g6,.2P7A2.110638901 STUDYSPONSOR E. 1 duPont deNPem.o0u.rBsoanxd$C0ompany(DuPont) Newark, DE 197140050 USA EROIECT `Exygen Study Number: 008.362 SponsorSty No: DuPort-11418 Toul Pages: 81 --~ - -5 Company Sanitized. Does notcontain TSCA CBI H25425: Subchronic Toxicty -- Supplemen1t ExonSody Nos08342 ESxtyudgyeninStRuadey Nwiatnh bOrn0e8--G3e4o2e,raconeRdeprTo5d2u5ct4i2o5n:EvSauinetoions,c"Tcooncd0eDfaory DGuaPvoang,e Raesspeearr.iomed fncomplies withUSEPA TSCA (40 CFR.pan792)byExygen Princpaal Ivigator Exygen Reseach --~ Bue ised SSuussAanMaMckeencKeri StDuodryoDnirector Doueqan-s00f S= imi SDpounrsoorRepresentative D2ue-203 Bose Reset --_ _-- Page20t81 Company Sanitized. Does notcontain TSCA CB 5100D25e1y25GaSvgee svye TosiihOne Grnrtion Brodin Evins DSuipteem 1 _ [---- QUALITYASSURANCESTATEMENT E BemgmniRns BeNeestmaatooomnSiayEviAstvTOsopniU,taSPieynsv cGoosxsoysSlStw oyyytoNRe uectrio0od 06or34in82n, eeCottE m!oteSn ei igsvr ra [OSDue a De=to=prtyo DN unnoDampi) Pirin toi own we 2 SE rstesrdT owes ome we CEi [fE=rotm ws ams wen ee ~~ 3. RawDaa&Draft 1027.28.29, 11/0603 1203 11303 Lydia al uals Date rhe --~ _-- J Company Sanitized. Does not contain TSCA CBI 9H02-5D4a2y5:GavSaugbcehSrtoundiyc iTnoxRiactistywithOne-Generation Reproduction Evaluations DSuuPpopnlte1me1n4t181 ExjgenNoS:0u08d34y2 CERTIFOIFCAUATHTENI TIO CIN TY "tThheirsarwedpo afftoorrtBahxegysteundSy,tacy Number008-342, i tueandcomplet representationof Submited by: 3B0r5y8gReenseReasrecahrcDhrive S(us1e9C2o7l2l.e1g0e,3P9A 16801 Principal Investigator, ype: Exygen Research Investigator iafs> Bae BxygenResearchFacility Management: -- " VJioche PMr.esFildaehnetrty Bxygen Research Wk Dae `StudyDirector, Duo: Susan Qa Kenge DSuusPaonntA MacKenzie 14-80-2004 Dus `SponsorRepresencative, DuPont: DSuvpiosnttkemsts 7 Bp Research 2y-sov-2003 Due Pagedof 1 --_ ee mre. Company Sanitized. Does not contain TSCA CBI H:25425: Subchronic Toxicity 90-Day Gavage Study in Rats withOneGeneration Reproduction Evaluations Supplement 1 DuPont 11418 --_~ Exygen StuyNo:008342 STUDYIDENTIFICATION 190.DayGavageStudy inHR25s42w5i:thSOunbeel-vGoenineeTrotoxnikRteyproduction Evalutons `SPONSOR STUDY NUMBER: EXYGENSTUDYNUMBER: TYPEOFSTUDY: `SAMPLE MATRIX: TEST SUBSTANCE: DePont11418 008342 Residue Rat Plasma Pentadecalluorooctanoic cid (PFOA) SPONSOR: EPL0d.oBPoon5x0tdeNemoanduComrpasny `PNheownaer:k,(D30E2) 139676-1542-5050.50 ~ STUDYDIRECTOR: `DSuusPaonnAt. MocKeazie TESTING FACILITY: TAINMAELTYATIBCLAEL:PHASE E30x5y8gReensReesaecahrDcrhive SteCollege,PA 16801 ``SAtvuadlyyIincatliSatiaonDDaatee:: 110000330032 `A`lyAicnalaTReeeplmoiryotCaoitmopnilDeaictoen:aDalt: 1110/01991/0033 --~ -_-- Borgen Reseach Page Sof81 Company Sanitized. Does not contain TSCA CBI 25425: Subchronic Toxicity 90Day Gavage Study in Rats with OneGenerationReproductionEvaluations Supplement 1 DuPont 11418 --~ BogenSindyNo: 08342 PROJECTPERSONNEL "TheStudyDirectorfo hisprojectatDuPontwesSusanA.MacKenzie. Thefollowing `personnelfromExygenResearchweressocialedwihvariouspasesof thestudy: Name PaulConnally EmilyDecker Karen isha Amy Sheehan ShasnRoto Te TechnicalLeadLMS Scientist Seentst Associate Scientist SempleCustodian ~~ Bxypen Reseaeh Pugos f81 --~ -- = -- `Company Sanilized. Doesnot conTtSaCAiCnBI 9H02-5D4a2y5;GavSaugbeclSotnuidcy iTnoxRiactistywithOneGeneration Reproduction Evaluations --_ Supplement 1 DuPont11418 ExypenStdyNo:008.342 [PROJECTPERSONNEL "TpheresSontneyl fDrioemcEtxrygeorntReisseparrojcehcwterateDasusPoocioattewdawsiStuhsvaarniAou.sMpacKhenazoifets.heTsehtedsfyo:llowing Name Paul Connally EmilyDecker Karen Risha AmySheehan ShavnRob Tue TechnicalLead:LOMS. Sciemist Scientist Assis Scientist Stmple Custodian --_ Exypen Resec Pugs6of81 --~ `Company Sanilized. Doesnot contain TSCA CBI 9H02-5D4a2y5:GavSaubgeehSrtoundiyc iTnorRiactistywithOneGeneration Reproduction Evaluations Supplemen|t DuPont 11418 --~ ExpStayNo 008342 `TOAFCBONTLENETS ase `GQOUAOLDITLYAABSOSRUARTAONRCYEPRSACTTAICTECEOMMPLEIANNCTE.ST.AT.EMENT corn32 60DDEESCO-- RFAINALPYT-- ITCALION METHOD.. .srwsoeoooomeo--m--om--o1}LL 62Preparationof Standardsand Foriicaion SOHAOR rr1 6L .5Descriptionof nsrumeat#50OperkingCY ONOR roeroorn 12 ~ 0L EXPERIMENTAL DESIGN... esse onrosmsssoonss15. 9.0 CIRCTHU ATMM AYHS AVET AFFEACTEDNTHECGUAE LITYSOR 110 RETOFEDATNAANTDSI AMPLOES..N. sees sersoronno1n5 LI OFTS ABLT ES ES TableL. Summaryof PFOA(ppb)inRtPlacaCBr)SETBIE .cvcv T TableTL SummaryofRecoveriesof PFOA (%) IRat lass Samples.. 18 TableIL. SommaryofResidueFoundfoc PFOA(pp)inRat las Sempics....19 --~ -- BogenReseach Puge7of81 -= Company Sanitized. Does not contain TSCA CBI 202H2-:5DD4aa2yy5G;GaavvSaauggbeeehSSvttouunddiyyciiTnnoRxRiaacttisstwywiitthhOOnnee-GGeenneerraattiiononRReepprroodduuccttiioonnEEvvaalluuaattiioonnss ~~ - DuDSPuuoPpnopnltet1m11e14n4111t88 Bi Sudyy Nos00a 8342 LI OFFS IGUT RES Bae Figu1r. TypicalCallrationCurveforPFOA... 24 Figs2. Chromatogr Repscaing aCalanSander okPFOAat 105g Figured. C~hr5onmga/tnoLgorfaPmRCepPrFesOeAnt(iEnagyCgoennrIolD:R0a3t0P2l2a3s9mCaonftorroPlFOA,ASweii:th103034)2.6 Figured. FCRhrOomAaatnogdr- 5nRyepmre.soenft"iCn-gPCoFnOtAro(lERxaygePlnaIsDm:a0F3o0xt2i2e3d9Sspt k1A0p,Spt:with Figw.e oCfiyPpCm.sPtFoOgAam(ERsepyrgeesneInDt:in0g3R0a2t02P6i,aSspnoanSsaomrpIlDe:f6o6r50P5F3O,ASwitth1=00n30g34)2.8 LAISPTPOFENDICES Be ~ AppendiAx. StyProtocolDuPont 11618(xygenStudyNo.008-342) nd Appendix'B `ADneatleytmiicnaaltMoentohfodPEexMn-0a08d.2e76RcevaisliosnA1o,cd"rM(eoPtFhoOoAcd)ofainASnnearclyusmiisbcfyorthe --_~ -_-- BonReseach Pus ols Company Sanitized. Does not contain TSCA C8 S102-5D4a2y5:GavSaugbeehSrtoundiyc iTnosRaitcslywithOneGeneration Reproduction Evaluations -- DuSPuopnple1m1e4n1t8| Eye SyNo 0342 10 SUMMARY. BaocgcoendninRgestoeaprcohto(cBoleDyugP)oanntal1y1z4e1d5s(aAmpppleensdoixfrAa)twpilnagsmtahfoscnraelsyiidaelsmeotfhBoFdOEAxiMn. 008.276 Revision 1 (AppendiBx. `hheemeitmihoodfvqaluidsaaafytoCnti0h6ios2mtn7et.hoodi 10 ppb, which wasesablaiEsxyhgeeidn ResidesofPFOAinth atpls samplesrangedfrom < 10.0 gb 04600py. 1"T0h0e%ave1ra1g2e5re.covery standarddevon for PFOA infortifiedratplansampleswas 20 OBIECTIVE ETxhygoebnjcsknivgetoheftmietshaodnByM-a00p5h2a76wRsevis0iaonnal|cyzieradtp"lMaestmhaosdaomfplAersryeclivoertdhset `DeterminationofeatadecAacido(PrFOAo)inoSeccu abynLMoSi"c, ~ 30 INTRODUCTION TnhislreapormtedtethaoidlsEheXreVsuElt0so8fRte.hvei2asni7aolny6sisof atplasmasumplsfoxPFOA inth "sTihgnesdtpdryotDoucPolons-o1m1b4e1rD8uwFeosnnti14t15d. TonheOcantaolbyetri0c3al,2s0ar2,dwthewsasthOecsttoyb3e,i2c03o, chesnlyica terminationdewsOctober, 2003 40 TESTSYSTEM TaosrceocnetiovledfutopmlDsuPouoetodnfo1co0nUtoAl.saOmnpelehsnadnidebdreatroycaontloalmoa iaimpssamwpelrees peorssiovnneedl3uBpoxyrgeecenioptnaSnedpptleamcbeedri2n3r,o2n00s5,rAgll(s5a2m0plCes).werelogged nbyExyge.n Ssumpoe logcwiintahntidicshaoidnyo.fcSuisrtaogdeyicnfoormdastwiiolnlcbaenbeopftaydeanthReersaewadrcthaspdac4ktaege copyofthe storage econ il befriahc ugonrequest. EpoResearch Fess -- = -- Company Sanitized.DoesnotconTtSaCAiCBnI 5 12500:v6 SgusSonya eTsei OntGenin Reprints D-- ig Pa pnp rss eeryesnd3e 5.0 REFEwoREs o NCEMA8TPEFo ROS AI)AwLt Fesis eSEteelnse TgieaarieSfo mtfoprfrewl td lov, Ths sic -- Erons `Compound wEEwE Exygen Inventory No, GoTssU,0 LotNo, PBuity (%) omoew ExpirationDate mhee nnofprosaic ad(ROA)a he clsidus hen ~ Zm _O iie = potas " nt 7 BC-PROA Chemical Name = Molecularweight = perfluarooctanaicacid, [1,2-4i-C] 416 . "Tel=H T+ HrAd Bogs non _--_-- m an--_-_- Company Satzad. oss rotcontainTSOAGEI 9102.5D0a2y5:GovSaugbelSvodncTionxRicaittyvith One Generation Reproduction Evaluations DuSPupopnle1m1e4n11t5 --~ BaSudyy Nog:006n342 60DESCORFAINALPYTTICAILMEOTHNOD 61ExtractionProcedurs 1. Miensss y0.1mLodfosadmcploe eto ,1 i.vcorpen-d1o0rscecofndsg) bes(ony 3 (Aadedcoemnionuggfhosctoonics svoolnumge tmo ebmesexttacnidonva0l0u0e55p00inL.. 35. CAoednnvtefyroesgafmooprrles10i0mneigsnoseesctopn1y4L00E0pMm.S. 2Preparation of StandardsaodFotifcainSolos CToC hneensttoo icokfsnou.rnom tafarny10)s0t uiunpminente LhoafbnyolGP.FoOTAihevnassgtopscepksacavrndiamraodnlSyoeplt1ie0mmnbeoerfo"f1G,tF2e0O0t3Ai,dewrads3 rpheeripoisnmofoanPlSROe1A0pme&geof1r0te17,sm2Ld0.0aw3asatrcoe3ucpsosnbcfyroripaokainnigof1i0n1m0ci0.hogafnnth..sbAaycfdkoirssfcailcdvaiaioogn eiolnuhiiomonnuaponfd0bSr1iC0nF0gmFilnOtwAiewthivaoslpucrmepesar5e.pd 1by 1a0kiinngc10nmL.ofthAe LtoOcpkp4ld.bfaognficsiohen ~-- Tn4a2emte1or0.0fTsgtahmnde.sPoFcOonAnssnilvnergosPvFsaOsAwhiefto1r.t0i mghile.senm"dpCai-roPdFssOawnesdshiporexnercciinbtedyecifaoolilrnoiwiononfg Candas, nialConc. `VolumeGul) DilutotGeald) "FinalConc. -- 110000 o1r0 ii Porr Tay 20oo.l5imoLnof0thiev1.08 pcogc/emnLza"t"iCo-nPoFfOA0s0o0lu8tpioanw.asoafdPdeCdFpFriOoArtionmcackihngfinal ohfeccpianit.TiohoehneasxtdarnedoadresdsgrsopsrsoctssssaadigrlaondgadhtstOhoveobeiwxnrekcdoinnpprgiocotehdnudmreel,tehefoodimvnltdeictohtens otonyc Ge y 0dhyr 0l0n o0-v2i7nn 7g. bTih:eforifcaionofthesandsbore,xicion + BoreReh Pretof81 -- BR. CompanySanitized. Doesnotcontain TSCA Call 0E2-5D0a5y:GavSaugbcehSrtoundiyc iTnosRiactistywithOne.Generation Reproduction Evaluations --_ DSuuPpopnletm1e1n411t8 BySudgyNoes008a342 "CoPOFOrA VFoolruimfei(oin) VCoownmoelof ECxotnaciosfd FoSroilcuiaoinon Sample(ul) CaSlnidraaridon I 001 . or io ooolt 200 ooi1 520 0a1 100 oot1 2100 sTohlueieoxntmoctdonbrsionlguitnigtonewvaoslupmeepuurpetdoby10t0amkiLngw0it3hsmie.iofnehe. 1T0hegdaill.uon"sCoAuFioOn v`woalsupmreeuppaeod1by00tmakLinwgit0h550m:L50omfetthhaeno1l0wuirp.."C-PFOAsolutionin bringingthe i"Tnhe8 rsteofcikgseanonrd(r4s2ol2utiCo)n wanhdeaalnlotiinufsi,cDatoicounsmtoanfedsairnadnsodtlaurtdiapornestpwareaiteisootnocnraend bo foundintherawdtsasocaedwith is port. 63Coromatography ~ "QTuhaonrifeitcaaiionniomfeoPfFPOFAOwAswaacsco2mp0lmisihe.dbwiytahnnaolyssiigsnuisfiicnagntilmeicrrfoesrraagypLcCk-sMS(</2M0S.% oftheLOQstandard)i thecontolsuples comesponding10thesaatrenoies. 64TtrumentSensitivity "1T0hpespbu.alisamo ofPPOA injctddurin bechromatographicrunwasequivalent 0 5Descriptionof Instrumentand OperatingConditions AqPuiEsiStcioinesxnLdCprMoScsMsiSncgowueprleepdetrofoarmHeedwlseintgtPAaackyarad1H.E2 LsCoftswyasrt,emwassed. Daa `Delileopectingcoudiion re stdbelow: . IMnaesfsaScpee:c:~~PSECSIECXIETXwbAPoLl4o0oS0p0rBayiLoigmudoInlrMoedsuccsiuAonnlIaleacrresrce Comper; TDeulolOpltoinplSeprxGayXtIeImp0erature =350 CwithN2at 7Linn SofLtcwa:re: FPeBwSiccitexPAacnkaartd:(HVFe)rSseiiones1.12 00 ErynReseach Pu 120081 ~~ _--_-- Company Sanitized. Does not contain TSCA CB 012-5D4a2y5;GavSaugbeehSvtoundiyc iTnoRsiactitsywith One-Generation Reproduction Evaluations --~ DSuuppopnlte1m1e4n1|t8 Ege SyNo:008342 HHPPVQauctupumumDpegasser HHPPCAouloubmjnecCtoomrpartment HFiPlLleCCCrotliudmge:(:Ge2nKeesyiisCony (HoynpeesrcCarhiincanmda,tex2iot.ingrgprmuamp5y0ym,), NCioobimlePTheamep(:A):320MCArmeriumAces wae Mobi Paso(3)Miehasel Tm0e %A %B How0(3almn 33s0 o 1@0 0033 7307 o 1100 0033 9705 " @ 0033 1550 " 0033 resin Vol: SuL --_ osmonitored: APuObAe NMoekge Toms4i1on3M-o3si6ored GIROA Negtive 415550 66 QuansotdExiampaleCtlcloatinon pFivxoewekmiicgerholiiwntagerosmfeotsfusrarimepoletaoaclhaleeibsertaatknidoanrsdeacnaudemsed)iwessraednjacecetedpdeibayikorTthoaeavLeCerMgsSsIhoMenS.oiTnohgfe, hqeucaonlcee)nraawiaonroefsaynyml.cTonheenreviadiooscnonofctnaedmonasfo tPFaOAnwiadngsdaAevlraemdined12ro(mo hefollowingequaion: Eeqtguorasoosfnosnm1wletrascmwepteeadrks)ogecaenltereiatieed btmyh hmeaoAnundnaatlroypfteasaokfawyaere)fporsnoigdnrgaitmh.pbstandagrfdcrvba(slendcacrn. Antefound(5p)=(Anal PkASpoapkeAa) x Sco. gl) DF Exygen Research Page Bott -- - Company Saniized. Does not contain TSCA Cel 02-5D0a2y5:GaSvuabgcehrSotnuidcy iTnoxRiactistywith One-Generaion Reproduction Evaltions -- DSuuPponptle1m4e1n8t| BypenSayNo008342 iFoerdsac mplea fritehl edpewrictel hnktnRowoe nvaem.ounts of alteproextraction, Equation 2 was ReEcqouvaetriyo2(n5)= `Ana fon`e(Apb)Amn=aalvoyt.Auanddaentd(7ot5u6)ndin contol zk).x100 Fowarsfuisekedstaomcpalleuflorttihfeiepdewrictenhtkncoowvneya.moutsofanalyteprior toexacio,Equetion 3 ReEcqouvateiroyn(:%)=alte fund5) vg. Anaviefon nsample Gob x 00 `AmountAniteadded G55) IADn0e3x0a2m2p3l9eoSfpiaAca(lScltui1o0n0w30i34g)aoraictiueadlsp10pepfbolwliotwhs:PRFOaAt.lsc splExygen Where: maopedkana = 81 SSpceok.a(repafu) =Ea41)67nginl. istleorpoecpt == oo0ni0swss ~ diptaidodnefdofoerlOeFv)e) == 110 mfomdinconmal = ND FArraolmyeeqfuoautnido(np1b) = (GOSBU/I4I204) 00104953] X4167x 1 0176029 = 103m FrRoemceovqeuraytion2 = 03h)x100 00 = os maotyeb:eTligshelxaymdpilfefecraelnctulratoimontwheavsalduoensesuhsoiwnng ironuLnedeRdnAuWnbDeArTs,Aan.d therefore BeenReseach Pass 4 81 --~ --_En---- Company Sanitized. Doesnot conTtSaCAiCnBI H5-02.5D4s2y5:GavSaugbcehSrounidcTionxRicaistywith One Generation Reproducio Evlustions DuSpupople1m1e4n1|t8 --~ BaymsyNo 0832 70 EXPERIMENTALDESIGN ECaamcnihsaowsoicfocncsaegtaenlwtasbs,eo,nnsaccetdraickloec(nornteio,dwesotthskbnoEocXwoMnrAyOc0o8.in27o6crRoe,vtiss1i9o:n201afineddd Sais, aton ld peextendpli. 80 RESULTS ThePFOAfoundinthecontolstplasmasemperlied aTable iInndTiavbleIeT. TohsavforgPFpOaAnitteecbooerisstr&ysoenidaidepviaatiomn soexpPlFeOAasids hte d acmswp e 100%e 41.2%. RIenshidiodsaorf sPFlOsAtnohrtPlROsA sinatmhplerst gpeadnrsoeml< e10apebgi0v4e6n0i0nT7a.bleIL FAigtyupriecal1c5b.esioncurv foPRO 12d prsntive chomsagras x ga in --_ 90 Ther sbknow icsaess ho avfc he ql ox neyoedt. 100 CONCLUSIONS TRheevritpel.as samples esesel syedssntomth EM-0:276 11.0 RETEOFDNATATANDISAOMPLNES oWmiheanbetnsheifgoie.l0edahrcscpoonmc,psoT,fhsldocgidnaaoktpmeeiarddweet3lSg8e-3nsegetcdbyEcoeyocnfasRfeocshdc3h1 : Reseyi spoitvnesdfaochge.ipodlyoftsnpecspeccifvieddat.4w0i CbFeRr.iPaond75n2.hREeyeed `samples ofreference substances arearchived bythe sponsor. --, Pe 15ot1 i Company Sailzed. Dossnot containTSCA CBI H9-02-5D4a2y5;GavSaugbeehSvtoundiyc TinoxRiactistywith One-Generaton Reproduction Evaluations DSuuPppolnetme1n1t4181 BgSudyNo: 008342 Bogen Research Puge 160181 -- = `Company Sanitzed. Does not contain TSCA CBI 0H:-2D54a2y5:GavSaubgcehSroundiyc TinonRiactistywith One Generation Reproduction Evaluations DSuuPpopnlte.me1n1t4181 --~ ExygenStd No: 008342 TableL Summaryof PFOA (ppb) inRatPlasma Control Samples `SpoDnsor (nPgFiOmAL) 666981961600CoConnttrroollAA211001/030130033 ND ND 866899116600CConotronl AAt210r1/00/o70/7l/0033 ND ND 856699118800CCoonnttrroollAA211000/088//0033. No ND Egon Reserch Page 170081 -- -------------- Too -- eee-- ------ ------ ------ ------ ---- Company Sanitized. Does not contain TSCA CBI 910.-2D54a2y5G;avSaugbcehSrtoundiyc TinoxRiactistyith One-Generation Reproduction Evaluations Supplemen1t DuPont 11418 --~ Baygen StayNo:008:342 TableIL. SummaryofRecoveriesofPFOA(%)inRatPlasma Samples rSpyonaer TES ATOR GPoOnN. AmuPnoFyoritad Cl 5s Parcosmey To aeseotrnan(ics2eSBp yoo1emas0nnsss oEsat oz wpeo oo k" a aeSsaiaor1eena01ccs3Sm4akr1o10on70S wwaro wwoooe kmd 14a5C09i08 nh110e088A5Bn5yo1o10r50R778S89.. o=mo Sas wThoeoo Tm=o 4G5a0o9 naces3spaioOmGm TR G101.08Ad tous. == wwoo I wo = " eeGsansnooa4ce5sAssapio19on00su8 s oowsne wwwooo b*bh eaasamonncessmotsous oomx i0"Wego"PA --- SRohre.e ma2 BcygenReseach Page 180081 ~~ I Company Sanitized. Does not containTSCA CBI H902-5D4a2y5:GavSaubgcehiSotnuidcy TinorRiactistywith One-Geneation Reproduction Evaluations Supplement 1 DuPoni-11418 --~ BorgenSudyNo: 008341 Table HII. Summary of Residue Found for PFOA (ppb) in Rat Plasma Samples Sponsor PF)OA 6506054074D7up. <<110000 666655004790. <<110000 665130 65076. <100 <100 s6so15. eso88. <<110000 sseesso1t4s8. <<110000 66655008888. <<110000 eesstoass <<110000 es06t50s43 <<110000 --_ e`s68s5t0814 <<110000 estos 665008 <<110000 e0e85s0o5r3 s20t2 65e0s7t4aDsup 250205 68p50y80 77 308 6e6a5s0183s0 ssteo pesse izn 73 430 e8s033 ses1z2 u2s Bogen Reseach Page 190181 ~~ TnCompany Sanitized. Does not contain TSCA CBI 9H:02.5D4a2y5:GavSaugbcehSvtoundiyc iTnoxRiactistywith One-Generation Reproduction Evaluations Supplement 1 DuPont-L1418 Exygen Study No:008.342 `Table III (cont'). SummaryofResidue Foundfor PFOA(ppb)inRat `PlasmaSamples `SpoDnsor PFOA (ppb). 685155 685073 582 549 665089 665110 47 a6 665137 665103 1010 845 665143. 665054. 500 840 665035 665160 868 #170 665006 665096 Dup 4380 4340 665082 e6s107 3640 2790 ess152 665120 4800 3620 - 666645909206 4090 4000 65162 85027 2270 2470 685158 685002 96 100 685067 665035 822 Ed s8s031 685146 80 257 685062 85138 2% 579 sesi12 885007 525 87 ses211 ND. -- -_ BrygenResearch Pag 20of81 5 Company Sanitized. Does not contain TSCA CBI 9H02-5D4a2y5:GavSiugbcehSrtoundiyc iTnoxRiactistywith One-Generaion Reproduction Evaluations DuSpuoppnltem1e1n4t18| ~~ ExypenSed No: 008342 `Table TN (cont). PSluamsmmaarSyoamfpRleessidue Found for PFOA (ppb) in Rat `spoDnsor PFOA (ppb) 65= 271 Dup. ND No 66655311778 wnoo 65230 665225 nNoo sesessa17t4e. NNoo sseess222718 NNoD sa6s5129017 IND 665256 65323 I no oas276 no no ~ 565260 ees180 nnoo sBe6ss322074 nwon e656522015 <<110000 65s2es1257D7up <<110000 s6a6s5224316 <1n0o0 sas320 ses332 <<110000 ees239 sas1e2 <100 <100 pe ses205 <<110000 BgReseach Page21 0081 --~ Ere `Company Sanitzed. Doesnotcontain TSCA CBI 9H-02.5D4a2y5;GavSaugbechSrtouidyc TinoxRiaclistywith One-Geneation Reproduction Evaluations DSuuPpopnl-e1m1en4t181 --~ Exygen SutyNo:008342 `Table TI (cont'). PSluamsmmaarSyamofpRleessidue Found for PFOA (ppb) in Rat `SpioDnsor PFOA (epb) 65251 865300 <100 <100 865340 Boss. <<110000 s6e5s314510. 2100 <100 sseess223580. <100 <100 se8s5127304 <61400 8e5a2s422402 0 369 358 castes oas261 8az0. e529! 68837 a8s3 ~~ 665333 65200 208 34 686655232160. 01021 seeessaasss2. <<110000 666655227259. ND <100 66655223070 ND <100 asa sss303 <<110000 sesa28 ess200 [ry <100 `BogenResearch Page 220181 3: Company Sanitized. Does not contain TSCA CBI H902-5D4a2y5;GavSaugbechSotnuidcy TinoxRiactistywithOne-Generation Reproduction Evalustions Supplement 1 Dupont 11418 --~ ByeSudyNoi 08342 -- Bg Research Pig 23ol) -- 56: Company Sanitized. Does not contain TSCA CBI '19205-4D2ay5G:avSuabgcekrSotnudiycTionxRiactistywith OnGeeneration Reproduction Evaluations DuSPuopnptle1m1e4n1|t8 aynStyNo:008342 Figure 1. Typical CalibCurrvaeftoriPoFOnA 1PRONUr gon TIES n 00831a OS) ~~ " | TTT TRE RRREARES BoypenReseach FEEAEE Pugs 240181 I CompanySanitized. Doesnot containTSCA CBI H02-5D4a2y5:GaSvuabgcehSrtouidcy iTnoxRiactistywithOneGeneration Reproduction Evaluations DSuuppopnlte1m1e4n1|t8 --~ Exyten Sy No: 008342 Figare2. ChroReprmesenatingt aCaloibragtionr Stana dardmfor PFOA at10ppb with ~ ngo/ f"Cm-PFLOA I EE m =am oo i EES Ey. Simi Be HE, i | --_ EE FE EEE m BeeWzE, -- ii Bypen Research P25 oll Te Company Sanitized. Does not conTtSaCAiCBnI 9H02D54a2y5:GavSaubgeehSroundiyc TinosRiaclttyvith OneGeneration Reproduction Evalutions DSuuPpopnltem1e1n4t18 Epp sty No: 08342 Figure3, ChromatogramRepresenting ConRattPlrasomaflor "PFOAwith ~ S ng/mLof *C-PFOA(ExygenID:0302239 Control A, Set: 1003034) EE=e EE-E Eb: EET: EES EF z EBe---RF2ECI | '% --_ es == . BE-& 2 Ei: BT | Epoch Pa 2605f1 PS -- CompanySanitzed. Doss not conTtSaCAiCnI 55025D1a2y5GoSgubSeyrnToRsacyith One Gein Reprod Bliors DSuproiTeira1 Sopslp os18342 Figured. ChromatogramRepresenting CoRnatPtlasrmaFoortlted at 10ppb withPFOAand - 5ng/mLof "C-PFOA(Exygen ID: 0302239 Spk A, Set: 1003034) I = =aeEE I [Sp fEitoC = Be "BF | ~ er = Earp 0 | [FE Biz be = bt [Fa TEE | Eas EE reas CompanySanitzad. DoesnotcontT5a0AiGnl 5250s25C:aSmupsahlyiosic OGronesirons DSpuebmaen Bop Figure. CoroRempssRtatPolasgSaeleoac PsFOA `with ~ ng/moLf "C-PFOA(ExygenID:0302026, Sponsor ge ID:665053,Set: 100303A) = Bi: | jz --~ ==E=E i rae | J -- I Company Saiz.Dos rot cotTaGAiGn1 1502-5D4a2y5:GavSaugbechSrtoundyc TinoxRiactistywith OneGeneration Reproduction Evaluations DSuuPpopnlce1m1e4n11t8 ~~ Eye Soy No: 08342 Study Protocol DuPont-11418 (Exygen Study No. 008-342) and Amendments and Deviation --~ ErynResch per = -_-- Gompany Sanitized. Dossnot conTtSaCAiOnBI 9H02-5D4a2y5G:aSvuabgcehSrtoandiyciTnoRniactistwyithOne-Generaion Reproduction Evaluations DuSpuopple1m1e4n1t18 ExSyoyNgo:e006n342 i 5Crs tyA525025. ScSnity ein-s | | | | i || fy"| | | - eeeeee ExperResearh | <A ied i Page 0at 1 -_-- CompanySanitized. Does not contain TSCA CB 910.2.5D4a2y5:GaSvuabeehrSoundiyTionsRitcstywithOneGeneration Reprodcion Evasion: DoSuoppnle1m1e4n1t8 --_ Exsuo:032 RE sensei nan be | -| - TABLEOFCONTENTS re i Demon | SCHoINGocowmsmmeeemesememsmseeammmsmmmeseas | ;; mmoumn oarreonu i! I NEaR AsAp R on, A P re--e ---- ] -- -- i E SmeeR -- S --| :!; | MBey E famne e ---- sa2am men a : sacronesoRoRssommma,mmmIOL___u mm mmen omen | | sors, | ErynReh _-- Paestost Company Sailized. Dos not containTSCA G81 B50a.sD4aays:GavSaugeetSonyi iTnoRntywithOne Gerson Rerun Evalusions DSuuppblemienet 1 -- ------ ps ri } i semen i -o i fTmTiemca, 2s5ee5 iTI T a0 scocnc, | i }i| NE opt ndte emyi Som oTdshi nhi m aiooi i | TE ed,E hei oR eof16mye ybS SvficoOVO) ay : hE ene TyT teeE ortTeL tpetiy i!i | . E SmTt Pp e e verpeater || om i omepose | stamcarbcenonsleAUSBATICA (0Cp7G | frS oedCg e p pie se VAtT aCrAeesAiarde re ii:i rm-- | Boye Reis Fast --_-- Company Saitize. Doss not contain TSCA Gol 2505. StrenTTooric on CononRodinris s-- amme) - sr pura: , == 30Duy GereButy bnhtwt ne ContosRepettobsbons ee | Thesadydesigns a fellows: EaDubus1418 " 1 l !| emPm orON oE sI oe oosw T0EE 5:i2 ! }| ER e | EB i -- B S---oSte ems TBorEtereerEas |i - ;ii E F Ei Rmr E ClinicalPathclogy W= EEe Ee" ;: | !i -- T=a s Sass(day 10) pwamna Alter 10diy ofdosing. S ie, HiTy, | RFay wEaei e er mtFr Recovery Week 18 i || somata nesta Sa Sram ases: esiTosi 0critpn eSseet ~ Soest smBenen sure ! . | MATERIALS ANDMETHODS t ce FeE E oeTT | fret oerepercannon E E C EE R E T T E E T ,| i| 1. Aviat cominco thepoi, comport, mosa ony,t CAS e, gisty i E -- pes . Maleendfms CHLCOMSDIGSBRrtillcoedfomChaosRiverLabor, t ~ ||| | a S E =EEUESe EE m EE Em EIm Se SEe T Sn Ra EE, RE . 8 ese) nddesignedfo i10d hepa chemicalsly. pe | upxpom ld ! -- | i . SuebeneSuty,FreoutogDoingPeo,PotweingPesod. 1 rte ---- ~ Conant, bosentan3ACl B RE o ates S-- mo si gi | E I e en IYmET mmbaRecdcS artvmosney asprmmtem- m-- re Tenoee : | YE Es ereni ee en [ ! Dea EEnmpm p e ~ |||!i 2 CageRackPosticning. E m o EmE e mE ee e .e irr willbereposticnedst eas evryoberweek: { |ii E pese en E e pummeme | tein. | 0Chiea Ew S08 a. + -- esa ~ 1502.5D4a2y5;GavSaugbehSvoundcTionxRiactistyvith One-GenertionReproduction Evalutons DSuuPpopwl1e1m4e1n|t8 -- EspNons06s342 ; Ef EA-- omen | |i ep t5omki aitt y bt iod ebday iii:roope | cr S m aa E endRtE sdN tdE ro fr ! top rtreerl ps,. i| Setramty ed ogee dfcone in CT i uttentiisrtipsStytre cemctpTpe esw arc i Sn eltR sdrI e T mgm ht iGrehege ] ~~ i D. rastreiod | pm m A Fl bs i 2b epg py . a atme tleh itihled 0 | + r Sern e raitsdbeeepgoiint te i| :| TT brhreinofh rconmi.tnM ein pem8 ;1| | ovE er a SegEE aTa pa I meNhki cE eoertopt ! || . - Some Research | Psssctst | -- -_--mmT$m-m--m--m--7 Company Sanitzed. Does not contain TSCA GBI - S ass.h oscooscoGoin rls oSpesnt --_ Somes irae Ee rs te & Aniprecme | i|| tsofehrxwil eldfre dy iof eg bodywihtpind. E E S R S T . re, feed roc acyepbehalmclogialsbeocalisesorclinical sige ofdisseoxiy.Tory |!i |JR mBa i eanwrediforgctachhste. rtmt dieEE | || Em E --ET --eErl i e T eb ey |! -- || R E EEEyS E paE i tS tiE . nga, Enc ais wi besigod nie itHas aniaemberad ndividucoge i| :i J| | e s CI E EEm E Ee Emo eEE e Set En r EE Ee n EE | ICS e mEiSeEE Sc STSt pSets tmESmEeIeItnEetRL !| | |JE y E mmsa eeE ssetE emeTest e----raul | | ey i RE nora -- Ee ComprSots, Swart sonsnTEOAGH 511025g425G,oSaubeShraonye iTnoRxaiscywith One ConranReprodustion Blain DSupiplaemesnt1 -- H--O -- se . , rE o S e i tt bAs rt i eR Tei r---------- ||;i: Di E afE oe a0re0ee, F-25425willbesuspendedin0.5%rethylelisloss ideonizndwater.Dosing suspensionsof i ! E D D E DE T r n E T a o . . EmL n a Le I EET Maesnd malocontolsmalwil be tytei with0.5% sylolilon ath mse ! ~ |I: SL E R loof chtdir n epp s wilh lC lec eRds, den dy:ebry || ET o eee a re ; | a soos fe r os lm ; ar r ie a i tiE e 4. h1ti : iTokCoamt nmt dory | EST, Daringthe sady,theacsoustoffoodconmamedbyeach afovertheweighingintervalwillbe |i F-- restart _-- Gompany Sartzad. Doss notcontain SGA Cal 1502.5D4s2y5G:avSaugbssSoanyicinToRxiactistywihOneGeneration Reproduction vsustions --_ DuSPuoppnle1m1e4n11t8 `ESxtudy y Nog.:0e 08-n 342 250%Beck Try i. e SrtTrId R ctfe T SE nie dS, N eiovES aS i| wpe Ane i Dmein =emcees, odccnp wl recs lorsfr | i| =+CrSS ehtiikn Driankh eeidtnioe d lodacenyn dywiTlbeem rin wit, ig ! j Grnpent Lidbcphitoo | + PLereaa p ittok o tbpinp itbe.mtel,dn mn . : 1 rdCheOhrid Dr pdtcete bt dt hdcdt cn ! --_ |i:i irate ey wiy haa attpree eraieismriyiSer iteonr8r0 . i! !|i| fP e m r e r e ei eY i | i rS ciierelvsiE ygnesootetmdwiE SldlboeremcpodR eed.peleny rioti0tydmlesa LY J| 1 os Tv igi msatb cyntbveaeyyfio ga,tet |! . ! prE E roopyE peEemmitrttnFrT get Er .Ry ain . | | ] Bor Rosnt : Revars: ~ DE Company Sailzed. DossnetconTtSaCAiCBnI JhrCoon tote Eos B-- eitr - ssn Emi tmp peas bes AE e me croe eoertra omr etre I | Aroort of findingsfom eachophkasioyexminsionwilbebitedbyhecrssiaing. | K. Neasbebavio!Baus. CE E e FE CinaiH msE e tOe--Ee Ey--eE E r--tn--rTeiC teeztt |! i recoveryperiod.Spar atewill edbeevaustdfo the intimalobaervaSicnalbeer(FOB) | | memes ~~ Sin1o. Smecsety MootforePrarsiyomn.efiona, pietpn wl 1i || EESESTESSUSImER i | ofevabasiogpup leinalinrtswd bia lightingcondions,pilsizewillbe : Tao | | A CEeSipprmmeieelsmR | `moni Crpvi bncscinotacsous themocihocsend ieofdayto D fHISEmESmmoE ETEmmoS iEinSAmA IISASeTEI IREEeRE | embedBoag chmo crywes | NE. ins ~ 7Company Sanz. sos otc TSAG1 1902-5D4a2y5:GavSaubgeehSrtoundiyc TinoxRitcsitywith OnGeeneration Reproduction Evalustions DuSpuopnplte1m1e4n11t8 PN Baye StyNo:06342 2E5E0ssaan compte L ClaryBassin -ovestin {i - i lgrmt ae BeityT ertiotettbcoesetCemeasymdcref gmyeinkd'CwoTipoiiaeysbs :i Eeatea Tiimanrteedeb edpvneinpvgse(0Gioi tnshhteetryybilceetvsedot vil { i|: A E lie oeisAsrtSBtEcowotn i :|: I1i Adda or od ed citn C amhmewnTocove iSPe.fSlaimle,dwtil boart pacopedotmere.ost 1{t | ET | uT edotE dycc RdiRpRoTEi SoT diS ri i ps is ! _ ; N ee ! | he ve iospmsin in |i m-- n JRrete taints ii |1 fNmaoE opeTmteT,IEBr Rc aeEi raanm , owneositodsIs SxpR d mEeSw | }i ESJ -- :i |1 aTeacton BopRoses i Pug statst -- Ex CompanySaniized. Doesnot conTtSaCAiCBnI [e-- ts-- tv Os ConnonerodesEars a Suen Sopsyn ---- i --| 3. SemCommi The tomosumhci I pest villedrm: - i |||I + A. sE EpEEactEsatnSsFEE O===Epro-- tic. PFE Eo e E = as ; tow-emteenp------=f--o . ~ L Poo=E E E=B ni ! De org ruentesrue EAE SEDTAwillbeplaced 1woeviaspio0 : || Lo p e L B Ro S im E n ass n s Sts etE , Ee a aOnLa i I e E t.e E S io. ---- ite --_ Company Saiz. DossnotconanTSGA G1 102-5D4a2y5:GavSaugbeelSitoundyi TinoRiactistyithOGneneration Reproduction Evaluations DSuuPpopnletm1e1n41t8 -- ESox dyNosp 06342 S3B508mseay dea cst pm Pmt ovrior !" TPlno.dvAdmiitltcedeneltebecoderf bpPaodcylen3,e i 1, 43i52k6. ; se E m deieT hg cin ot IIE Remisn 1 ! A N 3 JSS : erdeDfonemtcdpid 0 mek or ~~ i.i jOo oetye nipfeavewseecsTthfydefspfeombniEpis pihns i||! F mp 4 sciasr roay piE so let iwe-- i ETAT | Bi udot e atoo ertosinthof riescSeer, i-- i B roVg re T lotyy hsm--g 1 cn tdctsoii od sce. Ji ms ilshove etic Pr ei tintcn. | : Boge Reet Pers i --_ - = CompanySanitized. DoesnotconTtSaCAiCanl 5B025D0a2y5G: SaurbSibadaigTnoRxieacistywithOneGeneration Reproduction Evastions DSuubppl1em4e1n18t --BoStyNro 06e342 BSSSm Yosh 1a i| S E et>t Ge n R ie e m S t nr oe fa cn s f = " |! + TD mh mmte es gae tdy sp.ANeh, | i . ifnkrPR e c -- eernoietebesce iii e LnlL dnDmyter men hon isBa oiSmtEereRedSa 1 ST IIS _ i Powis -- emtcd lyid. || ii FB [e==5 4 Day21pospasts(WR os using) e a i i| | 5 re WgstDevens ii DE E ebenlatostst pne E mds hhaciriwe SECT | | rntht!tybdttptoienmfiandvty ees inl ' | | e E + mirS a T RST BopResch Pastas --~ ------------ GompanySanilzed. Doss not conTtSaCAiCBnI 50H.-2D5a42y5C: SaubcvhSrioandiciTgonxRieacistywithOne Generation Reproduvcsltuisioonns Du`pSuoppl1e1m4e1n|t8 Er SyNyo:08n342 508 I rei cette, posi .- fdrreiteeisensp tyedpasre bdo 3 riem i | EERE ; 0. Aeris ! i: SL trei tid |i }i} AeS otdo cclyE Hiie et me tdi i :} || fogA enyo hpaTm adremeTm d r ed Ei o E a rea nn:Toni hiT sbieTeweaamtest |i ! i i BpnRas --_-- Prasat, CompanySaniled. Dossnot contain TSCA CBI S525e02:GaSguboototi oRxbityihOeGerson srodution Pils PSoipptemeatt1 _ FR, EE F EE e m enone -- " | "bodyweightcn testday 0),orsaeificedbydesign. fm Sr p= -- i = foe Sof=Fptr =iza i E=E = Spo Eome . FoBBwe wersl T gmEebTE=mo. =H=E=oLrLe | Ue == SeUaemv,ne, D"Doommregrtiantors = plo cond vical, | ~~ . sews | B EE r E, | || Ae e l minwiitbhip c shpSropo pfivR te. s et oeHdt ine ts LE ie J | Bons mrrowmts wilbeppdth alcific malsein tsndwillbe, i | E SEEEEEREliRm SELEdEIcRSEaoEm, || J --~ _-- J CompanySantzed, Docsno cotan SGA GBI H-25425: SubchronicToxicity Supplemen|t BSlyn es08340 e ayaaspns over ! . F Stpo iisbr tS rEonswot tbeE01-- |p|e o A ietm t e heepsimbtoue i ewe t CLUE0, i eh I the santoofthepetologistodwilbedocmenid nefinal port. i RonAird ofTonBo tPrn iv i : EE ar rpetitt eee A eta TeAeea ee]TuL ettBAyy ;| nrataa tn eetaeeth, | -- y-- pe redeteo td lentic , Et |!|| :i u E hE nT e hii hOmk t hisbatenLetrnd | LidC entifi i kal scefdstad of oe spessimsioty 0-da cro peso wilbe | || + Beitbp seer | --a spratSipryei J Imtinin wareteeaes NerFeep Wehpop fs . | | han Woaslings eee 3uocft4 ntoaposawlildlebye.21. ||| `ExypenResearch. | Padlgofe81 _ ~~ Company Saniized Does no contin TSCA CBI 9H02.5D4a2y5:GavSaugbeehSrtoundiyc iTnoxRitcistywith One Genertion Reproduction Evaluations DSuuPpopnlecm1e1n41t8 --_ Ba StyNyo:00a 8322 | rere , BBEI:SeonTay ttttes nesion :Le ii A,p iralm edbyctodiemts cs B wil. | p: e a liming.Tri of3 teFoibnFsmraf e | {i| 1 FoSnramite evtetentntStp ioiomireeTnEiAPteekeSedskhihiEemaent,t ! :-- ; ottodit ct ec e fnesint rareeg a ole ta ds . t TER ew Eades ! A i Tt Ome Thread. ~ i| TSpod I Dire(wthcide) GrFoosneoris? ii fo : | eB e fr m i | i | 1 | ype Rees Pus atotst - Ee Company Sanized. Does not contain TSCA O81 52054D25G:avSaugbesSonyic TnoxRiacistyvith OeGeoersion Reproducion Evalaios DSoupnpele1m1e4n11t8 --_ EomasoyNacsa [-- . : pis csi ipcm cBa ef ofthe sendydnc oxpabelogist. i !| . otemb tOffiprinit g. eenat -----ppd i! freyeenpRVtyipe ipeieweir tty, i 5 0 re epi ps feMog coin. } --r | 1E E 8E pt4TF E A ityeE eE GitepinFerterempi, - i oe onglo echt edGi i ~~ ii EfE - EE maton km) i en I | mE conguegant) imn i oj=e oni i Sata J! i | SE vamwe er e hr d i pyete hand. SR :| i Eon Res - rr ii . pre --_ = CompanySaitizd. Does notcontaSiOAn GBI 51025025G:avSagee SvyeiTnoRsitcywitOeCenrnion ReproductionEvlotins fSsopsliemne)1n --~ Bogs ost30 H tngwI ileotS piea.ot r_r-- : p || TJ -- E rR a SrShe I 0m eile) we ody dymin | pre ms cnt E pi Les, 1 snpe 3 me tyneBe Anadditions!40CCeOMSDIBRG.aS(5retfwilebexobii aoeddfoo mChunrleesRi) ver i _ ||i:||| f E SSEErmSeuRe ebAIsnE hIai mheeA inezewS ersoT oee i ma l p nernt, || opbhulmoiogy namin),mlgmment0poups,bdyweighs,foodcoommption,mdfood i | offivrwight changes. : 2 Bbeiatiuts J S Ai ptn efenepee gentetind ] pEtrr e E iR mEs T | Be mi pli hdd Sted | { feerontemetwilelbecareed belo EsdaeemynTTbytheBord bod Fl odi -_ a ExygenReseach PageS0of 81 --_ e ---- tree GompanySaiized, Dossnot contain TSCA Gl 502-5D4a2y5GanSuabhSrtonyiiTnoaxiicith neGeneration Reproduction valu _ fSupeplesmenst BSo ly Nosn om32 jr A ae . STATISTICALANALYSES 1 |. Sema<8tMieteetmitaspp t | method orKineticsma willbedetrsiondafesstcy ituddorumesed slyrecord. | See rertsyas i = i : -------- i Ems = free[FT mes| E[EeEs . {| ER EEE| -- i Er esttia" | ||] F = -- e ar [t EE Ee RE| | | E I re w=] | BE N-------------- | 1 r BE E ee || . EE i ttn oe rl | Bosna Pasian ------------e-- sat-- e ---- -- 2905-4D2a5y:GavSaugbeehSrtoundiycTion iRactisywithOne Generation Reproduction Evalustions --_ DSuuPpopnletm1e1n411t8 BSna dyNo:g 00832 iEtesE seaTrs,oct torte noon .~ . ! nhnvtSedmetlpbeohfte cd ms .ii = ee ||i5 f E ire 5 i i E EoreR mE.t. m KEiN i | f EEhE : E + Ft E t A A e eeDett | | EE terhereon : Ege Rar -- i| Pu szotst | "8 spemyBDoessnnotioritenoTSdGAG.E! 9R02.5D4a2y5G;ovSaugbechSoanyieinToRxitcsitvyith One Generation Reproduction Evaluations --_ DuSpuopple1m1e4n11t8 FSa ud No:g 00832 Ss a ei ii: prrrahoeemspeeoernedeilhedetminontieydeodbpcddpoRrmrapttilao, ; | ImaTESmaE p mtsA es NS cT eeI8 R etd ennniny, edcrTh ! | emacs |: GE Trdodempm oe tsva ieptta oe id sir en , di i| [-------- Amet crfitetsTpeeapmdrteomse, : |ti --_ i foorre bi reh sYiea e o p0ooSo A iFraeiit ]i || akenl Lnabor. A xp of st metaswill colcedfrwcinspposes od. | | | : ---------------------------------------- |i BmRecah : Pes3ott -- --_---- TERR DorA 1ISCASE! 5205.4Da2y5G:avSaugbesSontiyciTnoRratisiwith OneGenerationReprodscion Evans --_ DSuupprleomenn1t ESv ty No:e 00342 stonsI are torre nema .- . B ROEDEFc PEAREC NCESCo oseOrPRr oOtttnsat OiCdR 15,7e (p99t. t I 3. Aptttiny PrAie s EC 90eOkrrt5om.nFvnw | . 5.Be d CR Q. ArRtRR fost tbg :} [ . E E foesm meT nb toyie meR edimitcr --otr--e Ps . .FomtT0a301t3t icoette,Ginstresitnd IR Se Se !i| 10Si a,a 055.Aim ey ps i S11 D ES Cvm . 2, 5ECo RmSiW0e97.nmSpthMfixoop6plir0s1 | i i 1S2KSEooA S wi kwT y wo,L tl tncs s. 1 RRonmX0o0a M.Seieeifm d t kMmt hTB mc: rtei r3413i5 d } |;i f1.F 0 o r ert e de ea ePier, i. Ht, :!i i : 110.SDauMeirhpSaoaArePhCSprpy,dHS.Rk.BiPi,uo5s,kA,M3yi1nid1RThr,A.sC(15e84e).SthihCnedieddn i | | [Rr -- | Pusshatsl "67 CompanyBoEadDag TTT 150AOBL 0H--2D5a42y5G;aSvuabgcehSrtoundiyciTnoRniactistwyithOne-Generation Reproduction Evaluations --~ DSuuPpopnlte1m1e4n11t8 Ba SudyNco 00a 8342 aesI samiTrEa gmttttbr Dosis : . i FROTOROLAPPENDIX i --- Suchen Sthen | Sty Di So Mocks SeeReseaTeeclogie i J] AsioedMaatmai |! i5 Nees rio: NLeitai tyToi i BeninAmir encOanTeg ! I. ClNieorabieoge od fe reeer. | ~ :| ReptAvs RBeomniraTe g !| | ntti ofTe SubstsoceAdmiiommicn October 15,2002 Seen tic soe ` EgonReach | | Pagessf 81 "&- omySarlzed. Dose not 571sA TSTA CH 5DeyG--ag--dy --RbithOeGerriReproinEins DSooppemen --_ ExygeaSadyNo:008.342 | -RE y e a sis sae i . ; coun = | ---- eeapae | | ots& Pie sila i | ~ |! o7.R ogrgttea Hf sai J | heHft t wes cia |: | (-- | \| i Cl . | -- meson _--_-- 8 Company Satins. Doss not contSCaAiGBnI [--lomo Sspiooans Svansyne | rede ||| |: | ||, | . | | | a Er --_-- ; mpm E f EopA rmaayrE e enCo |!:i| + Page5,MailudMethodsP.TetScansPresi i Adauismatio,pacagnph 1. REaiya:Thetongofi otsveschuagedtoscommodssworkchediesductng Be iI 2 PnMac nd te TPBL ri, i Ee TEREEEtRAEe A aTEpe Ee TSeal || a aa we nt | wo HRCE b Eso t ml o e, n | pestmdarcovry. nhCe gran J Sungeaiga i Seon . moran 510.2-5D4a2y5:GaSvuabgcehrStoundiyc iTnosRiacttywithOne Generation Reprodistion Evalutons LN DSuuPpopnlte1m1e4n1t8 [reTao com ret pe nein . t-- t -- ProtoenlsmendementNo.1, aI-- or smb. cn2,isamendedas follow (chasposbolded): ! B le tleet BevsSce oerTy,es dpi i ! ITA ii -- Thodeciron 0 evaluatelow anditecmedistodose ropawillbobasedon ers athe Tomttn tect piscseet pein | tSicRmtEtd tisdmg temi ! ESSe | --_ i tts O Suan mg temas i | on | |[ I 3| 1 Eph - PaoSoot 51 Company Sanitzed. Doss not contain TSCA Gall 2091.0.2-D5Da4a2yy5G:GoavvSaauggbeecShStrtouunddiyyciiTnnoRxRiaacttistywwiitthhOOnnee.GGeenneerraattiioonn RReepprroodduucetiioonn EEvvaalluuastiioonnss DDuSuPuPoponpnltet1m11e41n4111t88 ~ EryiaSady No: 06.342 Bes ren i" | J C _-- J i TT rtm smd om gl: : | || f fo13 r iemrete t.ed eer Bs,Cogenerd || ii1 B CBydieeletdh afm p eanceast yn q, imnl.se PaidfpCe oAFiR:) i TC AO FEt Emiat | i BR eisd:To oe insin dno cieth ymd rygon in oa --~ i 1 ! rnSG n l sgn | | | ExypenResearch Page 590181 --------------------eeieTespeeeeeeiseeaimes ee `CompanySaniized. Doesnot conTtSaCAiGBnI 5102-5D4a2y5:GaSvuabgeehSrotnuiyc iTnosRiatcstywith One. Generation Reproduction Evaluations DSuuPpopnletm1e1n411t8 -- EssapyNoes06n342 229 . "at i [I :. PROTOCOLDEVIATION __ + nC StEtEe: pris wmatemmmeorm | : T 22 | Ree | -- | fo RD oseifr ii |i 1.eWrestsecb LC toe erty red hd ris 2.tc pstctr cn ei rr ei Eee P[Bee ldir , aRkIe i ulnlo Ba : Eon | RI ! `BrygenResearch Pago60of81 =-- Company Saniized. Does not contain TSCA C81 5 veeSyRtithOn Geneon Reprodain Evins Dubs Ea SoyNo: 08342 Analytical Method ExM-008-276, Revision 1 "Method of Analysis for the Determination of Pentadecafluorooctanoic Acid (PFOA) in Serum by LC/MS/MS" --_--_-- Pugs of81 Company Sanitized. Doesnot containTSCA GBI B 25025: Seko iosc Co CogerionRertion resins ESpeeeln Sop os RESEARCH. . Tw -- \nt mEx ATire | Ssurse ! i| --- | sm Son 03 ; .i ~ i, } || oi i ane.mn |; he sonear - oxoss i|| | i| | | : . ---- EM0082761 1 oR \ i I ii ns EE Rr, sn i! rn _--Ye_ mm msm-- ----- ------ s CompanySatead.Doss not conTtSCAiGnBI ~ rc sree SE I MANAGEMENT APPROVAL i i FS i ExypenResearch | BBaeEsodhgh | ~ || EEE SV Eady = : | | . pe sims BxygenResearch. . i rzam } Pago63of 81 : FARES 25425: Subelvonic Toxicity 20-DayGavageStudyinRatswithOne-Generation ReproductionEvalusions --_ Supplement 1 DuPont11418 ErynsyNos08342 i TABLEORCONTENTS | yf GorEeEoAOL IIIT | |! Fe l -- -- GRR -- --e -- ---- ---- -------------- ii CBoumaese saommn m- aars s n: i. 33I3STS m reITmep S o aS Ba m S RESA) S------ 3 4 E3p33 CIATl A a-- ma-- n -- i Sa Aamm pow e}| ~ i: i T eTmERNSm oT n Gres T 1 18 4m .5S2E.TUmmBPIL-- E PARAMEe TE-- RS.ne -- ImT-- eTsis13 ! PE B Bo ---- T -------- -- ---- -- ---- -- ------ ---- Smo - i . rata wren t BonReseach Prestotl --~ Te Company Sanitzed. Dos not contain TSGA Cs HS02.5D4a2y5:GavSaugbcehSvtoundiyc iTnosRiactistywithOneGeneration Reproduction Evaluations DSuuPpopnletm1e14n1t|8 -- EaSyyNpose083n42 usToPTABLES - i Tle.Reco of ROAfio Roos nMkSee1 i i * usToFmIGURES ; | FPiE12.KCplivtincvoFpmEPFCOATrCIRos-- OtMNoneyS-- mee11 i : PE RapaoeCS ommit 1E37%Oh Ntbo Rt OAiTGoOs RE { Fie.VREeTtRaoiAmniCvirno-aSatgsaloofCCooPlMOoyoSeraFoifed #10 --~ i i i ie . BogenReset |ii Pagesors1 me `Company Sanitized. Does not contain TSCA CB sSaasys:GrSeaeoSriyToictiy hOeenero erodesElsins oSufpmiiniaeg PN Bonsprasrs3a ay | ! Te ope del mod of iisfo pefsoscasic id(FON) i .i TASTE CT :: ure 016 8 a 0 fe ThechecscalfocmabofPROA i veniasection2ofthsmerbod. A t | ommend te i etcinis sin |! mE eetE meT ot TNoTrrty |! ~ hp{ omi top n TATiRye II I | | | ie emp _ we} nosorn (Company Sanitized. Doesnot contain TSCA CBI 9102.5D4a2y5:GavSaubgcehSrtoundiyc TinoxRiactistyith One Generation Reproduction Evalustions DSuuppopnlte1m1e4n11t8 --_ Er StyNyo:00n342 i 2 EXPERIMENTALCOMPOUNDS - 1i Troesect,eeofen(c PFOA) ndto heft sd tandardws ii|! m ox a TW ! | cm fCraomlii-N xi puts sd 12651 ! e i ~ ii = THRey , sm Boys Reser } i | Perel -- hor Company Saniized. Does nat contain TSCA CBI 5H02-5D0a2y5;GavSaugbcehSrtoundiyc iTnorRiactistywith One Generation Reproduction Evaluations Supplemen1t DuPonc11415 --_ xy Sud No:008342 | Be > i 3 CHEMIANCDSAUPPLLISES - || 21. umacus SebaGE SHIEmeBiesa GIew i| AArioanf)e RWagCes SDiegs 0{ASTO Omisrves Wie Mises Wow { { 1 32.sn= aouson a { Teon SFoae { : ] -- I . | | . Lr eh Exp Reseach I od i . rern | Pastors -- a --- CompanySanitized. Does notcontTSaCAiCnBI astuay:GoSngoSrycTosicyit On CronReprints BppRm Spmsenronsn fr-- i re -- LSule ; | SE== mEiE nieamys pooTops |i . Ea Ee IEr mETaeEy rEioe,m) hs tt=i=NoEeapn mn i: |i oI me tm opee ns t ery et - : ;; NIsotesP:P eEPeErtmEroiE ei frcRe EerD as |||! ; i oDoE aodtobhemEan bfrI eiev. ee E sesE ttnR |f! FE Et nee tinseaue sme | | PR O T ETEL S--T-- O 2 mM mounsete soon Wn ppued by weighing | Ee Sopa ~ _-- mtn I rowan FS ---- [ ee-- TihOs opr prio inns aSpom - Besoin } --e{ | |:;|. || Pa i | .! 55 P Sou r FoRTICATENSITINS An+a yE=scEarttEoredpe oreE pps.r Ty T | tate LLG 10L200 ot AEt S comEmiEeEeE d rmi S sB S EtEeE pEm E Ee Ee E RReE EBSFReEa IrrAempSessnyrt p ee are sst f| a EE T rI tArevenues tyTS ; E B B S n R o EE Ei Entp E e arTy eITSNt || I S E EE REda E sayf--a o--m i E E =TpS rroE anE E eni7 iE iR onrgrs | Spates --i FE rer CompanySze. DossnotariSOaA Cna 910254a2y5:CaSvoabgeehSvotnidciTnoRxaictistwyithOne Geneon ReproductionEason DSuurpapnle1m4e1n18t BoNo:s 08342 ii --- ii i {|! ii | : i RI describedin 3.52.44840.5mLofthe 'C-PPOKsohiondescribedin Ce S B e me nF e dti o e ls pTGtn aSia LyE | 5E3c3.ElCviuelslRaiesssrTadeGthroocuatr,T ssh ||! o SToTehnn Vema e SGym SEamE : o wwm6l)oowBr Ha ou seo2he |{! } wow ow ow i errs SEE aes 4. METHOD % -- x -- ap on db hmbe, odby 1 ld Crctpiond men,Mtotroxac Ee respiis | Lon i in i| <a Simp Mu oslposm edbr mm ss.ITesTm , re | Somat nein | Bop Res Pnotsn ~ --_-- CompanySantized.Doss ot conTtSaCAiGBnI 514025a025C:aSvaubeSoync TinoRxaicswith Oe Geneon Rerodacion Evalusions DuSruoppnle1m1e4n1t18 -- Eo tyNo:m 00342 ee tia soredrefegaatedshouldelobeallowedlo eqilibatstoroom aitemperate. All Ce | "ol i ||! : : ~ 43.SvruaPRIPARATION ntof in etrch ch gt i | Ee EIlDE--i e--pe tC t e minexn1 tne ! 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Does not contain TSCA C81 H25425: Subehronic Toxicity 2-DayGavageStudyinRats with One GenerationReproductionEvaluations --_ Supplemen1t DuPont:11418. Bayg SyNo:008342 eens | |: UCiiSnaaEdaecemahdcnesyeafbscoctaoiotTatk.ssoLsogiviUecsvsriowdneitndiAcomfaaistr13 i ys iisb aoevmEL Tcihrcfiet cyimd eoeottvoa teesafebadni td2oeOasofn 3coe e13 | SGovmI s ER i i 3 5Toonarcsrosn2B0T9e8to5.itIcfbssa(ns)mfnosocetbss50cmcnviunssdpcopamsd,ime4s5be0 ; 454ii . mpmed cri 511 ht,sgl vey,oe i bums pcor pototoi mo concen vlutbe I} -~ i .AnceaTeyo ofceliatsonf itt iisstomdAiaetnssdemym8$,s1b0geemminigosof i i! a mnonvTnitoye,bcliicc:sOnsSepeanngbne fot d4 k Eoe m oem mnofch smie sos | : fprsri rotdBieesyaspf8eBesbronadchGee& pse i{i i poiroity f1Beead le toed ipsbrs 7 0 6 wl |! : Cb osiomoi pTalsketeBtadoldLiilaoppciys w(iotu deidm | i Sota enn} penReser Pug Thot81 -- Te `CompanySanitized. Doesnot conTtSaCAiCBnI 512054g25;GaSvugbeeSvoenyc iTnoRaitstwithOneGenernion Reprodcion Evasion DSuurpapnletmieanits PS BStyn Nos 98300 0 iSE | i. || : ~i : | ! masbut ar Jess ador hesthelowestconcratrtion of thicaibrttionstandards Ce 46 AccremanceCarma. + Thefollowing coecamastbemettoensurethe presenceof PFOAmd C- + J eS -- ap C.PROA: dsaghier on t 370sma fromm pareatof 415 cau. 2 AEenynRst pA rc thdbacks a et stS58Towe Yhi || 5p. Brrn oouphrpd npec mracypyeosamteewe n85. | om oree Sb Par Bi isntwrest e-exracionof heceimmlytcalsl. Anymusix spike b rI eor oeostE edto o A 0 + n rtsce tywhiag || o t ee re e st a tihe 5. Thecomcsoefiicenat (1t)foricaliobratnion carves gemeraed rust be. } Je<7onrnaggsmmrusctoomeass emssmy hyel J m pces Ruastandard no sc lu on on L E/MS ea er ahees is /MScomesponding totheestimated LLOQ t|1 Le Somers oven | Pesan --_ = Company Sniized, Doos not contain TSCA Gall ----hnGeto ReproBios oSssupppienr --_ Sapna rane | i SS S It s eb e mm se t. l . . ys T a as Jag |!ii 35eeine(1 ptcro, ionl, EE LT Weeyrarltis2 | vc : | a. oC sppn UseEuston 1 to ealciatstheumouatof ee analytefousd(in gil,basedon i iHrmicsniviqgon mm _ p an in- es me i|: i Epom 7 | LS Analytefound(poh)=avs.Analysefoundincontrol(ph) x 100% i| -- ; TEB E etErRisEon a e E ELpEoTnne] | of si rn} Ea nts --_ ee ttre CompanySais.Doss ctaaTSCAaGBI 9B02.5D4a2y5G:avSagbeeSonye TinoRratisivith Oe:GenerationReproduction Balusions DSuuPopwp-e1m1e4n11t8 --~ EuSty rNo:0e 832 C HEEFTTT | "Table RecoveryofPFOAfromFictionsInMorleySerum - i e Sema w PFOARachesmto10etmnaiiaSvs uevm | ir - DE) laeow Son Sew OW x : I. : [}! 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Rr-- Beans --_ --_-- Lo : i . reser | -- Company Santen. ove etna SOAS 552054s2y5,GovSaugbesSoundiyc TinoRastsiwithOneGeneration Rerodsction Evalusions DSuuppbleeme1n4t181 a. BomsayNo:0362 i | 5 | igur4e.RepresentativeChromatogramof Contes oskeySerym - i `Fortified at10ppbwithPFOAandwith ~ ng/mLof *C- i Eaeevee i =a ! = rn | i : | Br EET ) | ; i es BR | Pests i --_ I -- CompanySanitze. Dossnot containTSCA Get 2905.0D2ay5G:avSaugbcehSrtoundiyc TinoxRiactistywithOneGeneration Reproduction Evaluations DSuuPppolnetme1n1t418| ~~ APPENDIX B INDIVIDUAL ANIMAL BLOOD FLUORINE ~~ oe Company Sanitized. Docsnotcontain TSCA CBI % He 0 0... Brpss Bley8 gg&sssss3y samsm 3z8e8m8a8n 53233 Bf: 955% swiss s3iEE BRA : 2 Hu2 Cees "raw Lo... B5R583R3E8 -- 8 i;Ziis- ceees eee oe. CpoREER i: 14 E 2258% oo oo mmzzz J is 38.3 "sean ree Lo... 8S3H8E8N8 Js He oo o- o geEEg 23 3 3 Bod 2% 3 PR i "eeu Ce Tos2s8: i Hd : : 770 a2 Ee S3 inzss S7 mszss STsgsmss S5 zuzs "iZg& H ;ggEE 32 HTaE gesEH UHFRE AAR HSEFLYE 2= { i i 2x 3|] i |5] 0% 33 E3E Company Sanz. Boss ots T5CAG1 --~ zg = 82 "4 Lie HE Cee #0 ae ea... 0... BBEIR siz3F 23j8sgf) ssnmezszzz 8ze8z9s3s3 8s9s8sssyy snaasssa: 3if z 3 Ego z33yy sgEsy gmzmg gen -- a Es. ' 5 il: EF 3tee 5 | BEI ee. 0 i: .E2 i g i i 4 i: g 3 i] 83 lel 2 g g 1 5 33 BETA Zo = g 3 g 3 B : e iI ~Li3E 3:s3e8g8s8ss5dFs2y835I 8s79y r28E5385% 8L8y TsFes9eg8E8s |[i=4 CompanySats. Doss notcontinTSCAGo