Document gbozLE5vpzkvQa5vkmqx5XO7a

AR226_ 3316. } 498 AR226 3316 ~ Danae TRADE SECRET Study Title H-26137, H-26138, 2an8dDaH-y26S1t3u9d:y iRneMpelateRdatDsose DermalToxicity TEST GUIDELINES: U.S. EPA Health Effects TestGuidelines ` `OPPTS 870.3200(1998) Se`cOtEiCoDn G4u:iHdeealilntehfofretchtes,`TNestiangofm4C1he0pm(i1c5aa01ls AUTHOR: Carol Finlay, B.A. ~ STUDY COMPLETED ON: May 10, 2004 PERFORMINGLABORATORY: E.L du Pont de Nemours andCompany EHlakstkeolnlRLoaabdo,rPa.tOo.ryBfooxr H5e0alth and Environmental Sciences Newark, Delaware 19714-0050 LABORATORY PROJECT ID:DuPont-13882 `Work Request Novser: [an SERVICE Cope Novser: fl SPONSOR: EL du Pont de Nemours and Company Wilmington, Delaware 19898 USA. ~~ TTR -------- CompanySantzad. Boos motcomanTSA BI 2256-1D3ay7,SiHd.y26i1n3M8,lendRasHs-.26139: Repestd-Dose Dermal Toxicity --~ Dupo 13882 GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT `This study was conducted in compliance with U.S. EPA TSCA (40 CFR part 792) Good Laboratory Practice Standards, which are consistent with the OECD Principles ofGood Laboratory Practice (as revised in 1997) published in ENV/MC/CHEM(98)17 except for the item documented below. The item listed does not impact the validityofthe study. `The testfabrics were characterpriizoretdo the initiationofthisstudy by determiningthe quantity ofthe melt additive incorporated into the fabric layers. Although the characterization was not performed under Good Laboratory Practice Standards, the accuracyofthe composition ofthe `melt additive at concentrations documented in this report is considered sufficient for the purpose: ofthis study. Applicant/ Sponsor: E.L du Pont de NemoursandCompany Wilmington, Delaware 19898 USA. --~ StudyDirector: 4, (il `Carol Finlay, B.A `StaffToxicologist 10 fap otord Applican/t Sponsor: DuPont Representative Date --~ Toei mm Company Sanitized. Doss notcontainTSCA CBI 5252.6D1a3y7,SuBd.y26i1n3M8i,laexRaHts-.26135; Repeat Dose Drm Toy --_ QUALITY ASSURANCE DOCUMENTATION Haskell Sample Number(s): 26136,26137, 26138, 26139 Duponc13882 DatesofInspections: . CProontdouccotl:: NNoovveemmbbeerr 2117,,1290,023003 Records, Reports: February 6,11, 2004; April 19-20, 2004 Dates Findings Reported to Study Director: November 21, 2003; February 6,11, 2004; April 20, 2004 `Management: November21, 2003; Februar6y, 11, 2004; April 20, 2004 Reported by: Bulmer beBy Brobner `StaffQualityAssurance Auditor 7- ~~ _-- CompanySanitized. DossnotcontTSaCAiGanll 2356r1y3,So52y6i1n3M5,aendat2s6130 ReptDose Dal Toi Dwoisse2 CERTIFICATION `We, the undersigned, declare that this report provides an accurate evaluationofdata obtained from this study. ChtaPantio Fores D3VI3 PinRe o Sti DiplomateAC.V.P. S10 pRos E- 2004 ssn ) DyomiCFFrViBllCTLIA,M,GAPBST. eciry i fTye 20 EAvntooinreRaPeitnnyo toin kJ r FILAi) D Diplomate AC.VP. `Principal Research Pathologist andResearchManager L 27 Mey t 23004 seid SoFoFTialsvsaFD 2 02hux-2oot Lone byStayDirector: [aT dad Fenlee `Suadf Toxicologist 1=8ftnhuey 0 ~ Sarpy Soritons. Bossman TSOAGS H2-82-6D1a3y7S,uH-d2y6i1n3M5a,liendRa5s26139: Repeated Dose Dermal Toxicity A Dupont13852 TABLE OF CONTENTS Page GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT coarser QUALITY ASSURANCEDOCUMENTATION ccrrmsssmsesnsssnnnnd CERTIFICATION rset LIST OF TABLES cerconcmsssssnsimmmsnssssssmsssmsssssasssssssssssmnonn] LIST OFFIGURES tirana] LIST OF APPENDICES rcs] STUDY INFORMATION wossmssonsssssssssnessosssssosesn STUDY PERSONNEL cvs10 SUMMARY womans INTRODUCTION consents STUDY DESIGN. d2 ~ MATA.ERTIesAtLGuSidAelNiDneMs.E..T..H..O..DS c emo imr v ----e ------s --312 B.. TES SUBSIAICES.rrrorossssmssmssssnsenmnsssessosneos enon 13 D. E. QATUAAHUTSADAAOPAIAYCSNGorc s rons sos ssessrt14 FG..DAOSSE PSIIO10CGgrIoEuAp.s.aMr0 sSCnTrANYsnteerSIeL...meesmmmsomssoessorsrorersnoeeornoeeorooeoe1nn515 HL.BFOooYd CWEoIBgShUImSP.tricaronvdnrFnOoOnAcEinCeIsNeCsYsrssssssrsenmsmoornmssesmssoesmosroesmorreremooseonso 1S 15 J. K. OBSEIVANONS crores Perflu0ro0ctanAoCicd Level BVANBHON.........r.vvre osscnsmsios ose 16 16 L. Clinical PatholOgY EVAINBON M.Anatomic Pathology... hw.vi ..vcecevvvenrv--emrs--eno--msms--msmEsopsos--es --eo--s--1--6T RESULTS AND DISCUSSION w.cvvvvssssnssessnsrssmsmssssesesesmsssesensssesmmnnnsc19 I0-LiAf.leMTeOaXInCBOIo0dZyYWc eiandgBohdr yWteigsht Geinse ..... i s pr-- s --519) BC..CFloinoidcCal oOnbSsueanmdrDFepOrv0mIdaalEfiEFftfCeoIcEtiNsn,CYaondnM..O.s.M..,...........eovmossmsmsesesoseroreoroenren1199 DD. I0-Life COBGIUSIONS.c.crerrvrrtvsnessnnemenemssnsnsmsonoeneososoo 19 ~ ClinJ ical Pathology EVAIUAON vovevvcvimY smmssssssnosssosenensn2n0 --_-- pa `CompanySanitzed. DoesnotcontTSaCAiCBnI H2-82-6D1a3y7S,dH-y26i1n3M8a,laenRdatH.s26139: Repested-Dose Dermal Toxicity DuPoni-13852 ~ B, YRtlotls ygenpimmmmesmonmgens mg------ C. UrineFluoride... oe ------ A D. Clinical Pathology CORCHUSIONS oo mmm ADALOMC PathOIORY EVAINAHON creases20 B.OrganWeights . ssa-- mnt C. D. GrOSS OBSEIVALONS corr wms--------------r--il MICIOSCOPIC FIOv..rroesrrernnmemnnntmscsirseee 21 E. AROMIC PAOIORY CONCIUSIONS vrei 21 PFOA ANALYSIS srsnmsmsmsmmsssssmsmasmmmmssssssmsssssssmsnosemmonmsns2n] (COMPARISON TO STUDY WITH THE MELTADDITIVE c..orrsnrsssnmion22 CONCLUSIONSworrsemmssmsssssssmsmsmsmssmssmsmsmmnmsssrsssmssmsessssZel RECORDS AND SAMPLE STORAGEws23 REFERENCES.ccvosmmmssmsmmmosmsmssssssssessmemesesmtnesn3 TABLES csi FIGURES css) APPENDICES rosmsssmsssssssmmmsmsessmassssssmsmosnmmenndl -- -- a `Company Sanitzed. Does notcontain TSCA CBI H2.82-6D1a5y7S,tHu2dy61in38M,aliendRaHt-s26139: Repested-Dose Decal Tricity --~ Dupont13852 LIST OF TABLES Page `TABLE | MEANBODY WEIGHTSOFMALERATS... stmt TABLE 2 MEAN BODY WEIGHT GAINS OF MALE RATS... 2 `TABLE 3 MEAN DAILYFOOD CONSUMPTION BY MALE RATS. smi TABLE 4 MEAN DAILY FOOD EFFICIENOCFY MALE RATS... nn? `TABLE SUMMARY OF CLINICAL OBSERVATIONS FOR MALE RATS - PREDOSING.... 30 `TTAABBLLEE 67 SMEUAMMMJAIRIYONFFECVLEILNSICIANLMOABLSEERRAVTASTIONc S FOR c MALE Rc A~TPOSST DOSING... 331 TABLE 8 SUMMARY OF CLINICAL CHEMISTRY VALUES FOR MALE RATS... ccc 34 TABLE 9 SUMMARY OF URINALYSIS VALUES FOR MALE RATS... 3S `TABLE 10 PERCENT SURVIVAL OF MALE RATS ars p------------ 36 `TABLE 11 MEAN FINAL BODY AND ORGAN WEIGHTS FORMALERATS. 31 `TABLE 12 INCIDENCES OFGROSS OBSERVATIONS IN MALE RATS... ith PN LIST OF FIGURES Page FIGURE | MEAN BODYWEIGHTS OFMALERATS... a LIST OF APPENDICES Page APPENDIX AINDIVBOIDYDWEIUGHATS.L........ smim--------"-- APPENDIX B INDIVIDUAL FOOD CONSUMBTION vcr wen APPENDIX C INDIVIDUALCLINICAL OBSERVATIONS AND MORTALITY RECORDS... 54 APPDIE NDIVNIDUD ALCLIINIX CAL OBSERVA-PTOSTI-DOOSNINGS.... nn 62 APPENDIX E INDIVIDUAL EDEMA AND ERYTHEMA SCORES... 5 APPENDIX IANALYTICALREPORT BE 01 APPENDIX GINDIVIDUALANIMAL CLINICAL PATHOLOGY DATA re 165 APPENDIXH INDIVIDUALANIMALFINAL BODY AND ORGAN WEIGHTS... 171 ~~ APPENDIXIINDIVIDUAL ANIMAL GROSS OBSERVATIONS... -- --_--_-- Company Sanitized. Does not containTSCA CBI 2152-6Da1y3S7, t2inM6ya10kdR3a5t.s26613,9: Repesed-Dose Dermal Toxiiy STUDY INFORMATION Control FabricSubstanceTes: (QE Svnonyms/Codes: {~~ er Haskell Number: 26136 Dupo 13882 Known Impurities: (INR Physical Characteristics: Off-white to bluish-white fabric ~~ Test Fabric #1 Substance Tested: (RR . Submiter's Notebook Numberts): (SN HaskellNumber; 26137 Known Impurities: {JRE Physical Characteristics: Off-white to bluish-white fabric Company Santizad. Doss not contain TSCA CBI H2.52-6D1a3y7,St2ud6y1i3n8M,alaendRaBs-26139: Repeated-DoseDermal Toricity r~ Test Fabric 2 --p---- Svnonyms/Codes: DuPont13882 --_-- + H26138 Submitters Notebook Number(s): (NN Haskell Number: 26138 Composition: -- Known Impurities: [Il PhysicalCharacteristics: Off-white to bluish-vhite[IY Test Fabric #3 ~~ SubstanceTested: IEE Synonyms/Codes: Hs - H26139 `Submitter's Notebook Number(s): (N Il N Haskell Number: 26139 aa Known Impurities: None Physical Characteristics: OfF-white to buishewhif StudyInitiated Completed: November 18, 2003 / (see report cover page) ~ In-Life Initated/Completed: November 24, 2003 / December 22, 2003 oT Company Sanitized. Does not contain TSCA CBI F2-62.6D1a3y7S,uHd-2y6i1n3M8a,laendRaFt.s26139: Repested-Dose Dermal Toxicity DuPon13882 STUDY PERSONNEL Study Director: Management: CJeaarnoelttFeiaMl.ay,ErBh.aArd.t, Ph.D. Primary Technician: Management: James C. MackaIyI Janice L. Connell, M.S., B.A, CH. Clinical Pathologist: Nancy E. Everds, D.V.M., Diplomate A.C.V.P. Management: Jeanette M. Erhardt, Ph.D. Anatomic Pathologist: Greg P. Sykes, V.M.D., Diplomate AC.V.P., ACLAM, ABT. Management: Scott E. Loveless, Ph.D. Toxicology Report Preparation: Management: Sean M. Callaghan, B.A. Kim D. Birkmeyer, M.S. LaboratoryMVaenteargienmareinatn:: JTahnoimceasL.WC.onMnealyl,erM,S.D,.VB..M,A,DiCpHlo.matAe.CLAM, ~~ -- ios `Company Saniized. Doesnotcontain TSCA CBI F2L82-6D1a3y7S,tHu.d2y613M8a,laendRt5s26139: RepeatedDose Dermal Toxicity --~ Duron 13882 SUMMARY 2`T8h-edoabyjdecetrimvaelotfhoxiiscitsytsutduydwyawsittho dtheetearcmtiivneeiiftnghreedieefnftecwtsouthladtboeccoubrsreerdviendawphreenvitohueslacytciovenducted cmlaitneirciaalclhweamsisitnrcyoerfpfoercattesdainndtothaepolleyvpelrsopI ylene fabric.Ofspecific interestwered>e:rpmlaalsamna.d The fabric samples were identified as H-26137, B-26138, and H-26139. Eachtestfabric was applied to the days. shaved,intactskin of10 Agroup of 10 male rats male Crl:CD(SD)IGS BR rats fo6r wassimilarlytreated with the control hours/day for 28 fabric H-26136. consecutive The rats swteurdye.obFsoeordvecdofnosrummoprttailointyw,acslidneitcearlmiignsed,wdeeerkmlayldeufrfeicntgs,thaendstbuodd.y wBeliogohdteafnfdecutrsidnuersianmgpltehes. awtenreeccroolplseyctfeodrfaornclainilcoafyl ppsaltaihsomslogcyonpcreinotrrtaotisoancoriffipceerfolnuodraoyo2c8t.anBoilcooacdids.amAplllersatwseurnedceorlwleecntted gross necropsy and select issues evaluations were conducted. were weighed and/or collected. No microscopic pathology Tclhienricealwesrigensnoaterfifebcuttsabolne btoodsyyswteeimgihct,tofxoiocidtycooncscuurmrpetdi.onN, ofodoedrmefafliciireintcayt,ioonr wmaorstaolbistey.rveNdo during the study. --~ n`Tehcerroepswye.reTnhoeteclsitniscuablstcahnecmei-srterlyateefdfoecrtasdsveeernspereefvfieocutssloynwoirtghatnheweacitgihvtesionrgrgerdoisesntobwseerrevantoitons at confirmed in this study. However,rats treated with H-26138 andH-26139had minimally dreelcarteiaosnesdhicphotloetsrteeartomlenatn,dbmuitnwiemraellsyimiinlcarreaoseedffuercitnseofblsouerrivdeed; dtuhreisnegtwthoieepfrfeevcitsouwserdeeromfaulncsetrutdayin with this compound. t`eTshtemfaebarincslHev-e2l6s1o3f7@,iHl-l2lB6i1n38p,laasnmdaHw-e2r6e13395,.7repsppbec,t9i8ve.l3y.ppbT,heanldev1e5l9s.o3 plpbfiorrnatstheexcpoonstreodlto p`lgraosumpa,H-w2h5e1t3h6erwferroembdeilroewcttahpeplliimciattoifonqouranmteittaabtioolnis(1mo0fpcpbh)e.miTchael sionutrhceeotfetsthmeatSerliail,iins the unknown. UH-n2d5e1r3t9h,eccaounsdeidtnioonsoadfvtehrissesetfufdeyc,tsapinplmiaclateioantso.fthe test fabrics, H-26137, H-26138, and. --~ tee eee eee ------ Company Sanitized. Doesnotcontain TSCA CBI F-26137, H26a1nd3H.28613,9: Repeated:Dose Dermal Toxicity -- Bi DaySMT i eee -- eee RE INTRODUCTION The objectiveofthis study was to determineif the effects that occurred in a previously conducted 28-day dermal toxicity study with the active ingredient (a fluorotelomer melt additive) would be wobesreertveesdtewdhiennthtihsesatcutdiyv,eFm-a2t6er1i3a7l,wHa-s26i1n3c8or,poarnadteHd-2i6n1t3o9a.poIlnyptrheoppyrleevnieoufsabsrticu.dy,Thmrieldelfyabrics decreased cholesterol and triglycerides occurred in rats treated at 500 mg/kg/day. Urine fluoride wasincreasedin atstreatedat50and 500 mg/kg/dayand fluorinewaspresentintheday27 blood. ESSER 12spresentin the plasmaofrats treated withthemelt additive, Nproesteenstt ssutbusdtyawnceer-eredleartmeadldearnmdaclliinrirciatlatcihonemoicscturryreefdf.e"ctsOfasnpdectihfeilcevienltseroefE st in cE onductR ing thE e inblood plasma. STUDY DESIGN Group Number/Group_ Haskell Laboratory Number 1 10 F-26136 (Control) m 10 H26137 v 10 H26138 _ vi 10 H26139 Study Parameters Body Weight Food Consumption Clinical Observations Observationsfordermal effects MortalityMoribundity Checks Clinical Pathology NecRroypsy00d analysis Frequency Test day 0 and weekly thereafter Test day 0 and weekly thereafier Daily Daily Twice daily Week 4 WWeeeekk 44 MATERIALS AND METHODS A. Test Guidelines "The study design complies with the following test guidelines except as noted below: -- -_-- Company Sanitized. Does not contain TSCA CBI F2-82-6D1a3y7S,uHd2y61in38Ma,laendRaHt-s26139: Repeated-Dose Dermal Toxicity Dupont 13852 ~ + OfficeofPrevention, Pesticides and Toxic Substances (OPPTS) U.S. Environmental Protection Agency (EPA) (1998). OPPTS 870.3200 21/28-Day Dermal Toxicity. Health Effects Test Guidelines. + Organisation for Economic Co-Operation and Development (OECD) (1981). 410 Repeated Dose Dermal Toxicity: 21/28-Day Study. Guidelineor the Testingof Chemicals. ~The wrappingsof some rats became dislodged during the exposure period. Therefore, on theseoccasionstheymaynot havebeen exposedfora full 6hous. `This exception did not affect the objectives or the validityofthe study because, considering that no significant toxicological effects were observed, it is not likely that an occasional exposure periodof ess than 6 hours for some animals would have changed the study results. = Only male rats were treated. `This exception did not affect the objectives or validityofthe study because in previous studies with other fluorotelomers males are more sensitive to the toxicological effects compared to females. In addition, the comparison 28-day dermal study with the melt additive was conducted with male rats. B. TestSubstances `The test substances were supplied by the sponsor as off-white to bluish-white fabrics. H-26136 contained 0.03% melt additive and served as control. The test fabrics, H-26137, H-26138, and H-26139, contained 0.05%, 0.78%, and 1.46% melt additive, respectively. The sponsor marked the sideofthe fabric not treated with melt additive to distinguish it from the side to be placed against the animal. `Thetestsubstancesappearedto be stableunderthe conditionsofthe study. No evideace of instability, such as a change in color, was observed. C. Test Species On November 18, 2003, 44 male Crl:CD(SD)IGS BR rats, with an assigned birth date of October 6, 2003, were received from Charles River Laboratories, Inc., Raleigh, North Carolina. `The Crl:CD(SD)IGS BR rat was selected based on consistently acceptable health status and on extensive experience with the strain at Haskell Laboratory. D. Animal Husbandry 1 Housing --~ Rats were housed singlyinstainless steel, wire-mesh cages suspended above cage boards. = Company Sanitized. Does not contain TSCA CBI H2.82-6D1a3y7S,rHd2y6i138Ma,laendRaBt2s6139: RepDeoseaDertmaelTodxic:ity DuPont13852 ~~ 2. Environmental Conditions `Animal rooms were maintained at a temperature of 19-25C and a relative humidityof 30-70%. Animal rooms were artificially illuminated (fluorescent light) on an approximate 12-hour light/dark cycle. Excursions outsideofthese ranges wereofinsufficient magnitude and/or duration to have adversely affected the validity ofthe study. 3. Feed and Water `Tapwaterwas providedadlibitum. PMI Nutrition Intemational, LLC Certified Rodent LabDiet 5002 meal was availablead libitum except when the rats were fasted. 4 Mdentification Prior to assignment to groups, each rat wastemporarily identifiedby acagecard affixed tothe. outsideofis cage. After assignment to groups, cach rat wasassignedan animal number which was tattooed on the talofeach rat. The information on the cage labels included the animal `number assigned to each rat. 5. Animal Health and Environmental Monitoring Program As specified in the HaskellLaboratoryanimalhealthand environmental monitoring program, the following procedures are performed periodically to ensure that contaminant levels are below ~~ those that would be expected to imtpheasciecntiftic integrityof thestudy: + Water samples are analyzed for total bacterial counts, and the presenceofcoliforms, lead, and other contaminants. + Feed samplesareanalyzed for total bacterial, spore, and fungal counts. + Samples from freshly washedcagesand cage racksareanalyzed toensureadequate sanitation bythe cagewashers Certified anima feed is used, guaranteed by the manufacturer to meet specified nutritional requirements and not to exceed stated maximum concentrationsof key contaminants, including specified heavy metals, aflatoxin, chlorinated hydrocarbons, and organophosphates. The presenceofthese contaminants below the maximum concentration stated by the manufacturer `wouldnotbe expected toimpactthe integrofitthye study. `The animal health and environmental monitoring prograims administeredbythe attending laboratory anim veterinarian. Evaluationofthese data did not indicate any conditions that affected the validityofthe study. E. Quarantine and Pretest ~ fUp6oondaayrrsr.ivTalhaetrHaatsskwelelreLwabeoirgahtoerdy,3ttihemersatdsuwreirnegtrheemoqvueardanftrionmespheirpipoidnagncdaerxtaonmsiannedddquaairlaynftoirned -_-- Company Sanitized. Doesnot contain TSCA CBI F2L82D6a1y37S,tHu-d2y6i1n38M,alaendRaHt-s26139: Repeated-Dose Dermal Toxicity Dupont-13882 ~ any clinically apparent signsofdisease or injury. signs of illness, injury, or abnormal behavior. The rats were observed daly for mortality and dOinsetahseeobraisnejsourfy,actcheeptraatbslweebroedryelweeaisgehdt fgraionmsqaunadrfarneteidononme ftersotmdcalyin0ic(apllryiaoptorpadroesnitngs)igbnystohfe designee ofthe laboratory animal veterinarian. F. Assigament to Groups and Study Start Foclritniycraaltssigwnesroefsdiesealsefoeroircnsjtuturdyye,uasdnedoanbtohdeybwaeseisgohtfawdietqhuaitneb2o0d%yofwtehieghmtegaainn.,fTrheeedseolmefctreodm rawtesrweenroestdaitviistdiecdalblyysciogmnpiufitcearnitzdeidf,festrreantciefsieadmroanndgogmriozautpiboondiyntwoe4igghrtomupesanosf.10 rat, so that there 8Dowseienkgsoofftahgee.control and test fabrics began on test day 0 when the rats were approximately G. Dosing Procedure Ofrnomthtehdeabyapcrkioarndtottrhunekf.irsOtntrceaactmhednat,yotfhetrfeuartomfeenatc,hthreatrawtasswcolroesepllayssthicavceoldltaorsedxuproisnegtthheeskin ~ t`hexepsoasmureetpiemreiocdatcohpdraeyv.eTnhtoeraraltesxwpeosruertreetaottehdeffoarb2r8iccs.oTnhseeractuswtdeairyvese.trTehateeedaxtpaopspurroexpiemraiotdelwyas approximately 6 hours per day. The control and test fabrics were slightly moistened with `dmeeilotnaidzdeidtiwvaetewra,swprlaapcpeeddagaarionusntdtthheesakniinm.alT,heanadppsreocuxriemda.teTshheavsieddeotofttalhebofdaybrsiucrtfraecaeteadrewaith csohvaevreedadrweaasw2a0s%.wasAfhteedrwtihtehewxapromsurteappewraitoedr,. thEeaccohlrlaatrws aasndthfeabnrigcesntwleyrpeartteemdodvreydanadnrdetthuerned to the cage. w`Tahse rreatsshawveerde.rTeshheavaneidmaaslnseweedreedsdhuarviendg tohnelystaufdtye.r aTnheevaelnutairteioanr.ea that was originally shaved H. Body Weights All rats were weighedweeklythroughout of sacrifice (test day 28). the study. Additionally, they were weighedonthe day 1 Food Consumption and Food Efficiency `ITnhdeiavimdouualntfooofdfocoodnscuomnpstuimonedwbaysedaectherramtiwneadsbdyetweerimgihinnegdotnhceeapmoeurnwteoefkdtihetroiungchaocuht ftheeesdterudayt. ~~ tfhreombetghiennfeiendgearnddureinndgotfhtehweeweekekfraonmdtshuebtnriatcitalinwgetihghet.finFalrowmeitghhetsaenmdeatshueraemmoenutnst,omfsepialnladgaiely - = `Company Sanitized.Doesnot contain TSCA CBI 2HL52.6D1a3y7,StH2y61in38M,leandRaHt-s26139: Repeated-Dose Decal Toxicity Dupont13852 ~ dfaoioldycfoonosduemfpftiicoienncwyawsadsetcealrcmuilnaetded.. From the food consumption and body weight data, mean J. Observations ``wTehreeraatlssoweorbseeorbvseedrfvoerdcfloirnicclailnisciaglnssiagtnseaacnhdwdeeirghmianlg.effTehctesaDfrtairzreemSocvalaelwoaftshuesefadbrtioscso.rTehsekriants imitation. `The rats were behavior. checked twice daly for mortality and for signs of illness, injury, or abnormal KS cv: Evilution Blood was colflromethcevetnaecadvaofall ratsatnecropsyinto atubecontaining EDTA. IPlaIsma D wa2ssperxerpaacrteeddanfdrosmtotrheedpflraoszmeanbayt -p8r0oteCitnop-re2c0ipCituanttiiolniannaacleytzoendi.atrille.lThie caom--po--und "sWealsecqtueadntriefaciteidobnymolinqiutiodrcihnrgo(mSaRtMo)gr.apQhuya/nttiafnidceamtimoanswsassppeectrrfoomremterdyu(sLiCng/MexSt/rMaSct)edancaallyisbirsatuisoinng standards containing method is 10 ppb. an internal standard. The lower limitof quantitation (LLOQ) for this ~~ L. Clinical Pathology Evaluation `AThcelidnaiycablepfaotrheocloolglyeecvtailonuoatfisoanmwpalsescfoonrdtuhcetecldinoincaalllpaantihmoallosgy2e8vadlauyastiaofnte,rtihneitainaitmioanlosftwehreestudy. placedinmetabolism cages. collected from each animal. These Blood animals samples were fasted after 3 p.m. (overnight)andurine was for clinical chemistry measurements were collected Bflrooomdthfoer ogblta sinusoysfisewacahsacnoilmleacltewdhiflreomthtehaenviemnaal cwaavsa.unAddedritciaornbaolnbdlioooxdidceolalneecsttehdesfirao.m the cvleinniaccalavcahewmaisstprlyacaenddifnorafsreorzeunmstuebreu,mpwreocreesesveadltuoatseedrufmor,qaunadliftryobzyenviatsu-a8l0eCx.amiSnaamtpiloenspfroiror to analysis. analyzed. Results were maintained in the study records and reported onlyifthe sample was 1. Clinical Chemistry Serum clinical analyzer. The chemistry parameters were following parameters were ddeetteerrmimniende:d on an Olympus AUS40 clinical chemistry cholesterol wiglycerides --_ e ee e ret `Company Sanitized. Doesnotcontain TSCA CBI ZD2F-8y2-6D1Sa3y7w,SyHu-od26Mi1nd3M8e,iaerndRHsa-ts2s6139: Repested-Dose Dermal Toricity ~ 2. Urinalysis DDwuPeonst.i1s3852 Ur1i2nedivgiotlaulmpeH/wIaSsEmmeeatseurreadn.d Uarfilnueorfildueo-rsiedleecctoinvceeenltercattrioodnes, waenrdetodteatleurrmiinneefdluusoriindgesawBeercekman calculated (volume x concentration). The following parameters were determined: volume fluoride M. Anatomic Pathology `rAafttsferr2o8mGdaryosuopfsexLp,oIs,uVr,eatondthVeIIcownetrroelsaancdritfhirceeed atensdt nfabcrriocpssi(etde.st day 28), groups of 10 male n"eTchreorpastys,wtehreefufraswtaedssovhearvneidghftroonmathneuanfttreerantoeodnabreefaoarnedtthehierusncthreedautleeddasraecarwifaicseo.utOlnintehde.daThyeo.f eorudtehraonfiszaecdibfyiccaerfboornsdcihoexdiudleeadndeesatthhessiwaaasnrdaenxdsaonmguaimnoatnigona.ll tGrreoastsmeenxtamgirnouaptsi.onsRawtesrweere `performed on all ras, `The following tissues were collected from al rats Tver ~ kidneys thyroid gland Skin (treated) sgkrionss(uonbtsreeravtaetdi)ons f`iTxhaetifoonl)l.owOirnggatniswseuiesghwtefrienawlebiogdhyewdefirgohmtarllatriaotss:welriveerc,alkciudlnaetyesd,. and thyroid gland (after aGprporsosprlieastieon(se.wgh,icflhuiwdearcecudmiualgantoisoend,artunfeflcerdopfsry,amnidssfionrgwahniacthommiiccrpoasrctso)piwcereexagmeinneartailloynnwoats not (coel.lge,cotsetde.oaGrtrhorsistils,espioodnosdfeorrmwahtiicish,acmhircornoisccdoeprimcatdiitaigsonfostihsewotaull,dunrointabrey cadadlictuilvie,.and deformity oefvatlhueattieoent.h, toe, tai, or pina) were saved but were generally not processed for microscopic All tissues werefixedin 10% neutral buffered and were not evaluated microscopically. formalin. Tissues were not processed to slides --_ rr -------------- erpTe---------------------- `Company Sanitized. Does not contain TSCA Cal 2182-6D1a5y7,S1u.d26in15M,laendRtHs-26139:Reps DoseDems Toxiiy --~ N. Statistical Analyses Dupont13552 Significance was judged at p < 0.05. = Parameter tiny Test Ssiegnqiufiecnatial spplcaion sift E BFFBoooodooyddyECWWfoefnieisgcuimhmetpnGctayiionn evE ens tor oT Tepeee smsrmeode eifl--_--__--||KWi Pra--e ell-- comsppaesinscnn |OrganWeight iil Faoiony" TWhoeimvloegksfeoerfnpaoronserdmiSahltaipyyi?r"o-||DOvanurein-anwecaesyTM sefo5lll1yow5eodfwith ||DKtreusutsnk"safleo-lWtlatlolwiesdwith Survival homogeneiatnyd Sapir.|vaisncefollowedwith [1060followed with InciodfeClninciceal Observations| Wilk testfornormalit |Dunnett's test*1 |Dunn's test"? a Pairwisecomparisons and ssocitedpreliminaryetsweralyconductedif estfor ack of endwas Yb. W1ashi%egsnenisSfaihdcnaa.nptid.nIiovt-iWediuSlahklapoisbrstoewravWsaitlinkootntwessitsgnairfseicscoairngdtbenuditc3LnebteviKenrgeulssktsaelthwWaaansllscgeiatfcvnaansvta,lTuoael,rlcooableucsdutlbvayetDrisuoinnonnw'oesfrDcepkuc.nfoersmeedston -- plerfttohmreedcwoirtdhedthvaatlbei.lFiobirncdiaptal.e,if bilimbi was reported 5 0.1, 0.05 wa sedforsey cxuition --~ ee -- Company Sanitized. Dossno contain TSCA Cal 2H8L2D6a1y37S,t5u2dy61in38M,alaendRaHt-s26139: Repested-Dose Dermal Tricity ~ RESULTS AND DISCUSSION DuPont13852 In-Life Toxicology A. Mean Body Weights and Body Weight Gains (Tables 1-2, Figure 1, Appendix A) Noeffects onbodyweightsorbodyweightgainsoccurredinanygroupofrats. B. Food Consumption and Food Efficiency (Tables 3-4, Appendix B) No effects on food consumption or food efficiency occurred in any groupofrats. C. Clinical Observations, Dermal Effects, and Mortality (Tables 5-6, Appendices C-D) pi. No clinical signs attributable to systemic toxicity occurred. Ocular and nasal discharge were observeidnmostrats treated with the control and test fabrics. These clinical signs are considered 10 be due to the wrapping/collar application procedure. One rat treated with the control fabric, H-26136, exhibited swollen face. This finding was considered due to the collar being too tight. One rat treated with test fabric H-26an1dt3hr7ee rats treated with test fabric H-26138 exhibited swollen forelimbs. This finding was probably a resultofthe wrapping procedure. Hair loss presentin one rat treated with test fabric H-26137 was considered incidental and not due to the test fabric. Rats treated with both the controlandtest fabrics exhibited superficial wounds during. the study. Stainedperineum observedin one rat treated withtestfabricH-26137 was not considered duetothefabricbecause itwasonly observedinonerat. No dermal irritation was observed during the study. No deaths ocurred. D. In-Life Conclusions Under the conditionsofthis study and for the in-life parameters evaluated, there were no adverse: effects on in-ife parameters for anyofthe test substances. --~ = `Company Sanitized. Does notcontainTSCA CBI F2-82-6D1a3y7S,uHd-y26i1n3M8a,laendRa2t6s138: Repested-Dose Dermal Toxicity ~ Clinical Pathology Evaluation Dupont13852 A. Clinical Chemistry (Table 8, Appendix G) mTahelreerawtes.re no statistically significant or adverse changes in clinical chemistry parameters in the 8C0ho%laesntdero8l6w%aosfcmoinntirmoalllgyroluopwemreiannsa,nirmeasplescttirveealtye)d. wiHtohwHe-v2e6r,13t8heasnedcHha-n2g6e1s3w9e(rmeenaonts were tsthaetyiswteicraelloyfsuingcneifritcaainnt raenldatwieornsehvipertyo strmeaaltlmecnotm.pared to the variabilityofthe parameter; thus B. Urinalysis (Table 9, Appendix G) `There were no statistically significant or adverse changes in urinalysis parameters inthemale tatrse,ateUdrwiintehvHo-l2u6m13e8w).asTmhielsdleycihnacnrgeeassewderinefcoounrstriedaeterdterodatbse(utnwroeltarteeadttedowtirtehaHtm-e2n6td13u7etaontdhtewo variability ofurine volumes. --_ C. Urine Fluoride (Table 9, Appendix G) e`Tnhdeorfetwheeredonsoinstgatpiesrtiiocda.llyAsifgeniwfiicnadnitvicdhuaanlgraetss tinremaetaendweixtchreHt-ed26f1lu3o8riadned(uHr-i2n6e1f3lu9orhiadde) at the `minimally higher urine fluoride amounts compared to rats in other groups. changes were very small andofuncertain relationship to treatment. However, these D. Clinical Pathology Conclusions nUondaedrvetrhseeceofnfdeicttisoonnsocfltinhiicsalstpuadtyhoalnodgyfoprarthaemectlienriscaflopraatnhyoolfotghypearteasmtestuebsrtsanmceeass.ured, there were Anatomic Pathology Evaluation A. CauseofDeath (Appendix I) `There were no deaths. All 40 rats survived until the scheduled 28-day sacrifice. ~~ -_--Company Saitized. Does not containTSCA CBI 2H2561D37,SHt.2d6i138M,le0dRaH-s26139: Repestd-Dose Dermal Toric ~ B. Organ Weights (Table 11, AppendiHx) Dupone13882 `There were no test substance-related effects on absolute or relative organ weights. All individual and mean organ weight differences were considered to be spurious and unrelated to test `substance administration. C (GTraobslse O1b2,seArpvpaetnidoinxs I) . `There were no necropsy were test substance-related gross interpreted to be incidental observations. The lesions unrelated to three gross observations test substance exposure. made at D. Microscopic Findings Microscopic examinationoftissues was not performed. E. Anatomic Pathology Conclusions -- Under 10 test the conditionsofthis study and for anatomic pathology parameters measured, substance-related effects on pathology parameters for anyofthe substances. there were assis (Appendix F, Table 7) QBs present in plasmafromrats treated with the test fabrics. The meanIlgevels in plasma collected at terminal sacrifice were 35.7 ppb, 98.3 ppb, and 159.3 ppb for test fabrics H-26137, H-26138, and H-26139, respectively. The levelsof{iillin the plasma from control rats were below the limitofquantitation (10 ppb). It was not determinedifthe sourceofthe JJ inthe bloodcame from a@iMl source inthe test faborr riesucltsed from metabolism ofa chemical ingredient in the test material. - Company Sanitized. Donotceontsain TSCA C81 H2-82-6D1a3y7,StHudy2in 6Maal1endR3aHt.s28613,9: RepDeosesDertmaelTodxic-ity --~ Dupont13882 Comparison To Study With The Melt Additive A 28-day dermal toxicity study was previously conducted with the neat melt additive at dosages oobf0se,rv5a,t5i0o,nsa,nndu5i0t0iomnga/lkpga/rdeamye.t"ersT,hepraethwoelroegynopaardavmeertserese,ffoercthsemoantboloodgyiwceainghdtcso,acgluilnaitcailon `dpoasraamgeetseorfs.0@, 5E, 5v0,ealnds50i0n mpgl/aksgm/adawye,rere6s1.p4ecptpivbel,y.15M5i.l5dplpyb,de1c3r1e5a.s9edppcbh,olaenstder1o4l,1i7n6raptpsbtrfeoarted attri5g0ly0cemrgi/deksg/indaryatwsatsrecaotendsiadteSr0e0d tmrge/aktgm/endta.yrewlaastecdoannsiddpeorteednttriaelaltymaednvterreslea.teMdibludtlynodtecardevaesrseed. Inicndriecaasteedduerxipnoesufrleuotroidaendatm5e0toarbo5l0i0smmgo/kfag/fdluaoyrainded-ctohnetparineisnegncteestofsufblsuotrainnceeiannddawya2s7cbolnosoiddered `tprreeastemnecneto-fredleactreedabsuetdnochtoaldevsetresreo.l aTth5e00nom-go/bksge/rdvaeyd.-cffect level was 50 mg/kg/day based on the rIanttshtereparteesdenwtitshtutdeys,t fcahborliecssteHr-ol26w1a3s8mainndimHa-l2l6y1l3o9we(rme(aalntshowuegrhen8o0tasntadti8st6ic%aollfycsoingtnrifoilcagnrto)uipn Hm-ea2n6s1,38reaspnedctHi-v2e6l1y)3.9.UrTihneesfeltuworoideefsfwecetrsewienrceroefasuendceinrtaaifnewrerlaattsitornesahtiepdtwoittrheattemsenfta.briTchsere f`owretreesntofeafbfreicctssoH-n2t6r1i3gl7y,ceHr-id2e6s1.38A,lalndeHv-e2l61s3i9n,prlesapsemcatiwveelrye. 35L.7epveplbso,f9@8l.3lplpib,natnhde p1l59a.s3mappb. _ from control rats were below the limitofquantitation. CONCLUSIONS Ncoonsduemaptthisoonc,cufroroeddedfufriciinegnctyh,e csltiundiyc.alNsiogntse,sot rsudbesrtmaancle-irreitlaattieodnewffeercetsseoennibondmyawleeigrhatts, tfhoaotd rweacsepirveesde2n8tianppalidcoasteiroenssopfotnsee tfeassthaionndinctonhteropllfaabsrmicsfraopmplriatesdtdraeialtyetdowtihtehsthhaevteedstskfianb.ricMs.UTRhSere twreirgelynceoritdeestpsaurbasmteatnecres-.rIelnartaetdsortraedavteedrwsietehffeescttsfoanbrgircossHs-p2a6t1ho3l8ogayn,doHr-g2a6n13we9i,ghmtisn,imoarlly decreased cholesterolandminimally relationship to treatment. increased urinefluoridein afew rats wereofuncertain HU-n2d5e1r3t9h,eccaounsdeidtinoonsoadfvtehrissesetfufdeyc,tsapinplmiaclateiroanotsf. the test fabrics, H-26137, H-26138, and - Company Sanitized. Does not contain TSCA Cal ZDF28-y2D6aS1y3w7S,tiHu-dy2y6ii1n3MM8a,ilaencdRRHs-s26139: Repeted-Dose Dermal Toxicity 000000000 DDwuboonwt-a13s85e2 --_ RECORDS AND SAMPLE STORAGE Athlel sdpaotnasoarn.d records for analytical characterizations conducted by the sponsor will be retained by ANewsarak,moDpeflelaawcaehref.abSrpicecwiamsecnosll(iefcatpepdlfiocrabalrec)h,ivreapwurdaptoas,easndantdhereftianialnerdeaptorHtawsiklellbleLarbeotarianteodrya,f HDealsakwealrleL,aboratory, Newark, Delaware, or at ron Mountain Records Managemen, Wilmington, REFERENCES 1. DSuPtoniutnMHdaaslykeelRlaLtsa.borUantpourbyli(s20h0e3d).repBo-rt2,55D0u9P:onRte-p1e1a7t6e3d. Dose Dermal Toxicity 28-Day 2. DWrialpeeyr,,NNe.wR.Yaonrdk.Smith, H. (1981). Applied Regression Analysis, 2 edition,pp 266-273. 3. Selwyn, MR. (1995). animal safety studies. The useoftrend tests to JouofrthenAmeariclan determine Collegeof a no-observable-cffect level Toxicology 14(2), 158-168. in ~ 4. Jonckheere, AR. (1954). Biometrika 41,133-145. A distribution-free K-satmestpagleinest ordered alternatives. 5. Levene, H. (1960). Statistics (1. Olkin, Robust ed.) pp t27e8s-f2o9r2e.quSatlaintfyoofrvdaUrniiavnecressi.ty Contributions to Press, Palo Alio. Probability and 6. Shapiro, $.5. and Wilk, M.B. (1965). samples). Biometrika 52, 591-611. An analysisofvariance test for normality (complete 7. Snedecor, 349-352. TGh.eW.IoawnadCStoactherUanni,veWr.sGi.ty (1967). Statistical Press, lows. Methods, 6 edition, pp 246-248 and 8. D4u8n2n-e4t9t1,. C.W. (1964). New tablesformultiple comparisons with acontrol. Biometrics 20, 9. Dunnett, C.W. Staist. Assoc. 7(51,97809)6.-8P0a0i.rwise multiple comparisons in the unequal variance case. J. Amer, 10. Tunaemqbuaanlev,arAi.aCn.ce(s1.97J5.).AmeAr.coSmtpatairsti.soAsnosofcp.ro7c4e,d4u7r1-e4s80f.or multiple comparisonofmeans with 11. JK.rAusmkearl.,SWt.atHi.st.aAnsdsoWca.lli4s7,, W58.3A-.62(11.952). Use ofranks in one-crierion analysisof variance. 12. Dunn, O.J. (1964). Multiple contrastsusingrank sums. Technometrics 6,241-252. ia Company Sanitized. Doesnotcontain TSCA CBI F2-82-6D1a3y7,StHu:dy26i1n3M8a,laendRaHt-s26139: Repeated-Dose Dermal Toxicity --~ Dupont13852 --~ TABLES ~ = -_-- `Company Sanitized. Does not contain TSCA C81 F2-82-6D1a3y7,SwHd-y26i1n3M8a,laendRaHt.s26139: Repested-Dose Dermal Tosicity --_ TABLES ABBREVIATIONS: EXPLANATORY NOTES SummaryofClinical Chemistry Values CHOL - cholesterol TRIG - triglycerides SummaryofUrinalysis Values UVOL - volume UFLU - urine fluoride Dupont13852 NOTES: `Summary of Urinalysis Values --_ rGoruonudpesdwtiotfheiwdeenrtdiceaclimvaallupelsacmeasythvaanrythien svtaaltuiestsicuaslesdigfnoirfsitcaatnicseti,cablecdeatuesremitanbautliaotne.d statistics are et---------- eEe T rie SSE ---- Company Sanitized. Does not contain TSCA CBI --~ z a 5 8 88 8= _ 3z 5& |8 3 i3 2=833 ~i g SF oE nmE nnEgEnE s 2 2 3: FE i5 zZ8 F1&L8 ss 5s 5 5 = 2 2 8 28 2 E0ZT %odE4 RggRmFd3 RoeR 5dEeinRBees g= : :i 5=B8 83 02 20S8:o2f8 8af8 83&88 of 38 833 , oF 78 58 Hi 3d%E 32%% ggeu gddg ogmd KgEd | 391 2 2He82es2 ilEH i 2% 02 22 5330 80|=3i i: 5: id: 4 . CompanySanitized.Does not containTSCA CBI ~ 3g 2 3 5 3 35 35 5 3 ~ 1 3: CE : z 3 Z32 5 & 8 a 2 Hx 8 3 3 35 35 8 3 oI oS nf af a5 4F 3s gn z= EL so EE l1 ii 2 2 F2l 3 gs 23 ~33 F2 E2: LEE35E35E3 25 23 g3 y 8 "EGE 8 gf a ge is i : AE gz iz i :E LE E FREEEEEEoEs G5T: SEFEs 5 s 85 5 sg i : 62 88 E 3 & F # i 1 ii 2 i: CompanySanitized.Dossnot containTSCA C81 ~2 3 g 8 Lo...3 g F ATER aan JEH FHEEAE ~ | E3 si REE |. 4?s l iz B PSsISEzRza5RaE8l,2 1. 41 io HI 1] il 2 <s 42 gic ro lfFi8z es | g1t1 ij 3: ~33 ii moans. Sonnetsma ~3 53 5 s 53: 8 s g =222 3 pol 028330 EE AS 23 : 3 2s.g 2&.2&.8s&8 = _ 36gf F32EET aya A El ~ ' - F7g .lgf n2F En2E.a3 a2an.E8 2E8 r ]3 a3n)2 | 133fi e ! il : i E i] 21 i izq i GFsFs :88gg | dl 5 $5.0 fF: gd #32 8% 88 5 & 3% ELLEN| 3 {i ~37 gE 2 pr SaBoao ~3 a : A2 Eg g 5 2 g _|# 2 g2 Eee 2 "| 14 ~ 52 i: 4 fr og ii z 8 if oo 3 Lo i HH ' i:1 23 0isa5it g 3 Bi: i gs 3 de oe eo fErd lis 2 i PoEob Bf Hh i Poe: fir PE HH gs HH 2 [Es2 i Si RPE PH iz3 HELoiOF FET OFaE fi CamparySvs. bos otariCaAGn1 ~~ 8 i 2 g& F aE : gaEa. ggl a-n2 g=zm - 2g -- D3 o: Zh HSI L ome g2 I if : ~~ g 3gE sos... 2 25 gg si:kf L:sosL L f= FL 3I* I 3 i Z = & FI g :gi drowLoL. L2 o. . g 3 EE3 "2 LiF o fi 3: g:3 gz2 25 gt Py sf | si dips 2 Hi 3 8 gfegf 3 gdp HIE GH SHH i82iz2z] iLB1EEi7P df =88 io8up3f 3:Fo} :si5 } CompanySantized. Donotsconstin TSCA GBH ~2 z 2 g i g &525 gi3gs - . > . 5: 2g = NE HE 3 Zz Zz i Es ~ Sggg HHig: &.? c3 FE = E : H iis ig{| 382 sls olfTo lsEd 9fe]d i g 53% i 8g . 2i2g2h 23 y5r i 5 cZ 5E5h8 Ia i 5 is3 Fis gis a 3iif3 [sii 34 FE SHE 34 Ei SSideEiaddl y [ERT I ~iE BE 5 ju Company Sanitized. Donotocontsain TSCA Cal F2-82D6a13y7Se ,uHd-y26i1n3M8e a,laendRaHs-s26139: Repeated:Dose Dermal Toxicity --~ TABLE 7 MEANNGFLEVELS IN MALE RATS Duwpeonnts13882 FFaabrbiice MMEEAAPNNLASSMSDDA..SiRO(NNppb) H26136 H26137 <10 357 0 s4 10 10 H26138 H-26139 9%3 266 1593 53.1 10 10 cNSDC.msmtandabrd deeviatrion ofemples a linitofquantitation = 10 py -- - `Company Sanitized. Does not contain TSCA CBI H2-82-6D1a3y7S,tHu-d2ye 6i13M8i,laene dRa2s61: Repeated-Dose Dermal Toxicity --~ wDuPoonrt.1n3882 TABLES SUMMARY OF CLINICAL CHEMISTRY VALUES FOR MALE RATS -- CHOL (mg/dL) DAY 28 TRIG (mgldL) DAY 28 --_-- Group 1 HH-2I 6136 " 910) EF 11010) Group II H2H62611537 a7 1200) 30 10010) Group V H2H-62611388 ES 9310) 28 1200) Group VII HoH2e6l139 38 8010) 27 6010) Dua arungedas: SMteaanndard deviation (Numofbvaeluers included in calculation) `Therewere no satistialysignificant differencesfromcontrol at p< 0.05. -- --~ --_-- Company Sanitized. Doesnotcontain TSCA CBI 2H6--26D1a3y7S, Bt26iu1n3Md8i,lyeanRdaHt-s26139: Repested-Dose Dermal Toricity --~ DuPont-13852 TABLES SUMMARY OF URINALYSIS VALUES FOR MALE RATS ------------ UVOL (mL) DAY 28 UFDLAUY(ug2)8 -_-- Group1 H2H-62631366 89 47010) 101 27010) Group Il H2H6-21613377 13.0 7.1010) ns| 19310) Group V/ H2H626113388 12 95(10) 136 44(10) Group VII E6H-12631399 79 28010) 132 41010) : Dutaamingedas: SMteaanndard devinion(Numberofvalvesinched icaleuon) `Therewere nostatistically significant differencesfromcontolat p < 0.05, -- --~ -YY `Company Sanitized. Does not contain TSCA C81 DH2lL82-u6D1aw3y7SS,e2y6d1im3n8eM,aelaerndRsaHs.ss26139: Repesied-Dose Dermal Tricity ~ TABLE 10 PERCENT SURVIVAL OF MALE RATS Group: Material: 1 H26136 m H26137 v vi H26138 H-26139 `Doa0nTyesst 7 110000 110000 110000 110000 -- 2114 2% 110000 110000 110000 110000 J00 jo jo 00 ANluimvbeoernattessttdudayyst2a8rt 1100 1100 1100 1100 NPeurmcbeentroSufrrviavsaalt=i(sNku=mbNeurmobfeartastsatluidvyes/tNarutm.berofrats at risk)*100 `There were no statistically significant decreases in survival. PS Dwuroosn 13882 ~~ - Company Saniized. Does not contain TSCA C81 ~ 8 533 3 a gEFpriisisa Zg 3gg = 8 = g og% op 88 F3s E3 E3 23s 5J8B F iEE ss i -- z g 5 s Zz g R 5 g 583378 8 s fEsrzaz om E o : i fdora 5gdz I: gg 3 3 533 gZ3 of5 $5 5= . Z133 =Po8 gff8 o=z 2 a 2 & EB ~2g34 CompanySata. Boston5iAaGn1 ~8 & gz 3 g_ EfiisosgE EEos 3 "3 "ws Se es I: g E oq5p AF 88 EE --~ =8 z2 E 3 4' 5 F35gg fa82s28 os33 o3sg8| 3:S Iil i2 " 855 58 a3 :i i : E: ies ii gz gBOE3 GE8 iosE x ox Bx |4dz i . af 3 gf |B i2 iii --~EE EE CompanySarton. Sosnt rai 508Ot ~% z gEET op lgTlErEe Im Re EEs fog Eeio-eeieie ifE zag lal iri zazazsit eo fH Brinogrrrin ~ iz | 1 ih $ go 1 if IH i Hqg 3i5 f is 5 --~22 Co LENE g | iPogi i | | EEE PoE EE EE fi ii Di dFE Eo28dEsBE isEE it(in2 } 3 lgeEssi Eee ae gd | ummm eek tc sme ermsem meen YB Company Sats. Soe conan3AGBI 2H-82-6D1a3y7,StHu-d2y6i1n3M8a,laendRaHt-s26139: Repeated-Dose Dermal Toxicity --_ DDupuonto138s52 FIGURES --~ ~ - CompanySanitized. Does not contain TSCA CBI ZEEE 3588 tek ; | | e | =| 5 i 8 |L3Ig 8 = = i= IN|| | i2 I= g : |E-- gz 8 g @ wonfromone -- 2266-1D3ay7,SH-t2i61nu3M8a,ldienRdaytH-s26135: Repeated-Dose Dermale Toxicity DDvupoonnti138m82m -- APPENDICES _ --~ -Y `Company Sanitized. Doesnotcontain TSCA CBI 2H-82-6D1a3y7,StHu-d2y6i1n3M8a,laendRaHt2s6139: Repeated-Dose Dermal Toxicity --_ Dwupoont1w388s2 APPENDIX A ~ Individual Body Weights --~ -YYY DV `Company Sanitized. Doss not contain TSCA CBI ~ 83 = i 1.8 Finn ~~ i 5. amram 538d one i5 LF Tir s gE mEmanm 1& pfo aEmEu 35 2 E5d4 25 i: zmzzszasss 3 CompanySantized.Does ot conTtSaCAiCont 5ii aw ~ i wptaetanr 25k > Ei | iis oman i BI Gn :: 4 Ri prt 58 sf. 24 ~2E 2 1 giEsiii f oossssss F 3R3zEsEEss 4 Company Sanitesd Dorotsconsan TSGA OB ~~ iaT iisa Euf2n i3E 1p EEE iFi1pie s Em En E i4i ifir .smn i 5z KRSRANEARS s ii li. Ig) fe oadssemae pMHe fo HEFEEE CompanySanten. Boss tema TOGAGBH ~ 4g. HE af #3 if 8 ji HE EHHES P{z| 2i.be1 EmmEmuEm } i La 3 5 Edessa ii s3283c8fo1I7otz;3 EEREEdEiREEEEaEnE dali i spezsgaza CompanySatz. Bos ntcontaSiGnAGSI 2$:52-6D1a3y7S,uHd.y26i1n3M8,ieanRdasHs..26139: RepeDaosteDeerdma:l Toric -- Dupon13882 APPENDIX B - Individual Food Consumption ~~ -YY Company Saniized. Doesnot contain TSCA C81 L2Eb66:u1D3aSy7e,Sd5y2y6i1in3M6M,eleaRnRdsaHte.s26139: RepaDtoseeDecr-! Tuicity 00 0 -- INDIVIDUAL FOOD CONSUMPTION EXPLANATORY NOTES Abbreviation g/anm/day = grams/animallday oDuwponta138s82 =~ ~ - Company Sanitized. Does not contain TSCA CBI ~ gl. HE g ~ iif . 1 2] 2 Tip somenaumes H4i OEBe meer ama BEE 35 5 2 2B: snl orSattnt spotomGaTann ~ 4. i 5 Ii ~~ 83% Anszgdsdas f iF g : iH853%. g53d1s7n9d5s7d5n5g0 Bio mmm : i3, HME E58 ~z&] 2 BB mam BF387 os Ts ieee # B2323233887 4 2 CompanySis.oo etcnn5c ~ ; 3 al i ii ac ~ 3 i zi :: X iiin HqEeRnRasEaReNmEaRyS i jBin GEERGERE 3 Hr ERE i23,EL 8 eeemsenee s23il:= B7I 8 EEA os Fo # [ES S---- ~ al i --~ i . I i I 8. 25 22: Hr 23 2 i dagRRagRdR iBBB dmsndmdndmsss iE mmnmas Jef Lo: [adisiass i sspazsease 5 . CompanySantzad. Doesntcontain TSCA Cal Z0 DH2-8o2-6Do1a5yu7S,btBy-u2od6iyn1M3dM8,aeaerndReaH-ss26139: Repeated-Dose Dermal Toxicity 00000.DDwupeonst.t13s85e2 --~ APPENDIX C ~ Individual Clinical Observations and Mortality Records -_-- Te Company Saniized. DoesnotconTtSaCAiGnBI F2-82-6D1a3y7S,tHu.d2y6i1n3M8a,laendRaHt-s26139: Repeated:Dose Dermal Toxicity -- Dupont13882 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY RECORDS EXPLANATORY NOTES Note CClliinniiccaall oobbsseerrvvaattiioonnss rreepcoorrtdeeddipnostthi-sdoaspipnegndariexnwoetrienrcelucdoerdd.ed during body weight collection. ~~ -YYY `Company Sanitized. Does not contain TSCA C81 ~ 3. gl 823 i FE] [SEIS UI J I TS DE SD 3 ~~ Error oro: ror oro: os ' . FI EF| lf3 0i%, #&P3r2 2i8 nz& zo&i 3i2 :o2 d32i;d8 I $82Fo0go:5 1 0 i iI 03 i 2 :g FE SEEfRfEf ERfEE2 ER8E Ew REsNEaNT 31 giIREErEiEsERiEoNi]niIiRiEsEiEiEEtlEiEiRlE] ed :s Pfiliespilspisspidspidcgiifgidiyiiiggiigigs iy FIS EIEIEREEEREREREREREEEREIEIEERIELEIENNIEG] EE i: #08 E3EG8o E:5 sosof... 3 2 35 LLL . 333z LLL. ee. CompanySanlad. Does otcontain TSOA GH! ~ 4. 8 i i Eleaf elelefat2analialalat3 i i ~ siEFririoi riFiFooiEr og P[oIo: og: ' iii g FSllosi z z > 2 2 z o Z > x i P 1E 30nii.]0431 z |i S| 3 P 7 oifrfsf2ii2ti5s2 i2i8i%ei2ei:ei;sd3 :Z fiFfrerEdiiurElidpaibigriiiigriiciiiiiiyciiigniiiigiiiglid i83 y d I EiiSa g S dg EdRE NgEEeig NGE iEg Eii Ei iE Ed Ei e Ed EE q Ei aEdRE c d Ets BHf:os,i: +o: FozR ozo: E52 3ggoz SE Ps po: os ogo: EEE oss oz fo ---- ~ 5 82d fia i ~~ : i :| 1, 5 Fa Hi S007 Ge : [RE] EX gBEiEIlE: 2 EI <a&la & 23 21is, i= 3 [------ ~ &; i pPfsti.rse.l.a5l.i8.a8l.ela5.l5a% gfe= li=at, i 32 . ~ PITT ror: oz 3g ' zIE P-fFrE&E&iE p f&P EoFtE & R 2f& I fz2i E3&i.f E z 2 z2E82 4g i i i ff Pf 43 ff fF 2 5 2 FF 82 2 5F 2f 0% 5 3 i ; iii ififiiits tines : PsriBEfEffEiiRydSiiEraRidRaviiRrgEiiRgrR iEEtiRgrRdiarRiiEgaEiiys 3g i] .FPEIsEigRiiREiRiRiIiEiRiEiRiIeNiGiEiRgIiLaLsG gBsE; o#I8: %os 2 8ss3 8ss 3 .gE .2 .3 =Eos. =. oo LLL ILL Company Saniized. Donoteconstain TSGA CBI ~ gl 2: HES fi 3F3 rsf.d5a.l5.a8l.a5l.e.t3i.cal5at#aze i g - 8iPorro: os HE : &' zfl 0s g: fFF ifr FFFFzfrF o:F3Of ioF r f ozirsii,g i[I i o:zo 3 <Fl 5 8 3 &P8E Poff EoT of ioi3s80og 4f1y 53 " 2 2 2 sii ; 2 fFEiffiidlfeiieti isissigs I jrfrprpsEii aigsiicg iniiield] : Po3li2 Ei3 rirsi8yvi ii dlyiv2igi BE iz EE REEiRE lEiERiEEiRRfEIiRiGEiIEiTEiIRiEEiERiGEiIEeGiLcEGe gs; EA2f3f:8 fF 5 2 2 :z zg 3 i Ps os0o8: fsF os5 og EI Fog 28 Fos= CompanySanitized. DossnotcontainTSCA Csi ~ 4 al 23 i iletza loi f$ lo:31 1; 2Fl i 22 2% 2} B3l 7 gIErEiEsE t : jsi2g58s2 Is iii 25 5ES3E ii:, oz HE HH =&la 8i = = Company Saiized. Does nocontainTSCA ll H2-82-6D1a3y7S, H2t6i1n3uM8a,ldaenRdaytH.s26139: Repeated-Dose Dermal Tanicity DuPont-13852 --~ APPENDIX D Individual Clinical Observations - Post-Dosing ees `Company Sanitized. Does not contain TSCA CBI --~ ZDH2-8e2-y6DS1a3yu7wS,uiHdy2y6i1inn3MM8aa,llaenedRRaHta-ss2613~9:~Repeated-DoseDermal Toxicity 00000000 DDuwpeonwt1i3s88e2 INDIVIDUAL CLINICAL OBSERVATIONS- POST-DOSING EXPLANATORY NOTES C`mlaitneirciaall o(bfasberrivca).tioCnlsinriecpaolrotbesdeirnvatthiiosnasppreencodridxewdedruerirnegcobroddeydwdeaiilgyhtafcioelrlreectmioovnaalroefntohteincluded. -- ~~ ee TTT Company Sanitized. Doesnot contain TSCA CBI ~~ gl: if Fi EEL dE III Ee SEE. 8 EE A 38d i -i 3 FI 3 iiii ii 3i ii iz xi 2 2 z Bslf #b2e: 4b4i3e% 2l1s giitsd 2Z :8 3 =2 3: 23: ~Edl: S PC fi:E Fo; ofE ii osEiS EiEogoi $PgFi i53@Cg g:liiiosg3fiigfo;g:d 8 88 2 : o% gifo; of 88 a 38 2 da 83 aa8&3s & & i: EE 3 z 3 3 i= == = = = Gompany Saniizad. Doesno containTSCACB ~ EE . i FEE IE MI LR & ~ ii 2 i3i 3i i i Ti d o 3ii ' E z d3 ix ys 43 2I 3z SF; Ty Gli i, Blog; 4: #4107 1 32 P P2Fg g lgaEg 2fgr 2of 1 ogf:r 1 &58 SP iE2 fE3fF; Bf+S;%3 ff: yf5 giii::i2tiii5 io:d 28g 2 82i3:t 2 %2&8 38 8 2$3858 2: :& 8 23: i8f 32 38 2BI5f:: iio x, FFE I] :3 2g ~88F i. oo. . [A R---- ~~ Pl HE i ; i [iFIH g 3iPood3i 3iF 3 3:f ' E i lPy g p qd igal l oyi1,1 bd = I Fe E fT 2 2 % 2 } fBp Egid ppd gpl op 23 XN 8 7 8328 34238 228 338 23438 coin Skin Smt --_ iE Hasdd il Pi EIL En AA i II Ike SA SEES IEE ~ i ii 3i 3: 3{ ' g z E & 5E1l1 i 3 $i: 31,305.d;1 3:FE 2 3 Blo: (di: 09%: 5 i a cE Pie iE 2 i 3 EN i 23 ggpiing io1i1ii } $ef:f 38Edt Gpaeftd:oz PiB:iifoi: i & BPEEFE xE1I. iPiRiEES o0fB OE1E1ECiE%E6 2iH2. 8 22 $38 #338 3 3 3 3 32 3 8 1, . . 5- ~3Ff4EiF i: ss E 5 . - PoE os CompanySaniizad. DoesnotcontTSaCAiCanl ~~ 4 il i 51. i i TREE si. i3 3od 5d5 i ii i gk gi ffiii g3f3: i, 7 2: ~~28:: Li=L Company Saniizad. Donotecontsain TSCA Gol ~~ 35s it i 2 ~ i. s FiI g 3i . Eo: g 3i i3 3i g zs 8 2 i o FiI 1do 3i r a oe 3 2 d $53 i giisipl iiogi:gftog i3 sieei iifiatsd2 niig =$ ig 55g55l:s: H22H: E32 sTdi Fi El Ff s Eiiisisiii i ideod dPFE 0 iF f3 :eigl8 ig8 iifitiooi: fioiio;f: 1i- ,: 3 o3 3. o3 > 5 >. HE = = = = Company Santzed. Goss mt contTSaCAiCnE! --- 3 al &d i 2 2 ~: : Prog 3 3 3 ' 3 2 zglo:ig o2z7 o27z giir3g 285 i& - 53 3 5 i Fe ig EEfiEgAfacPiie ing2 fFiigs: sir El ppl geil 3 s 8 3 ; & 2 3 :2 s ; 8% 3 Ziz y $$83f3 83% F83 R 3E:3 3E:93 3 R 8 2: R % O fZ:2%i % l =3z 5 AEE gl I : copied SommerTSEATE ~ HE: ij as FRIES. i i z| 2 : z il i3 v 4: Hoi: 4 ior 1 [A < fg gd i8 ii: ioi%i Is. 5 32 iz 2EH35sIN - ~E2g3|2s i1 = = CompanySaitzed. DoesnotconTtSaCAiOnBI ~~ 25 i F Z ISIEEMIREEIIEINI,I z ~ iiio 3 33 3:33 3 3 f FI z| : & [I &i 2 2 i 2 lid iD pnb EAE I OE a Sed : i $3052 $ fei fe i 2 1g iiingsfong 3i JiEf i EO}Pgo3 fPtp ibEpEiaggiiiooisogiyi : TIE ELE op i oglagdioogg i22 EEEI E4H ~5g|3 $438:2 2 2ii2 3i:i t fs 5: i= = FI z 2 PiE os :8 i5 == = = Company Sanized.Doosno contTSaCAiCanl ~ ii i i ~ |i Ce as ; i i 3 i i Hgl IRi E IRE g251 Ii EEEiEEE RIFE EE 3! Dfirdgdidi d1a dg4 i3 g048s Eiiid g i fePgii gi si iodpg biffoi ajpdpg epl rfiipl i Er lipilii bE 328 3 gHl i:f ii : SE : z 2: z 5:i3 CompanySanitized.Does notcontTSaCAiCnBI ~ 3% if fi is i ; --~ i 3 gi| l:3 i 1 3 : 2 Ig i ig & $: 3 3 84a 2 Bog, EF ~ 8 2ga3l 2 fg w 28] &= . Gompany Saiizad. DossnotconTtSaCAiCBnI F-26137, H-26138,and H-26139: Repeated-DoseDemmal Toxicity 28.Day Study in Male Rats DuPont-13882 APPENDIX E -- Individual Edema and Erythema Scores : ne `Company Sanitized. Does not contain TSCA CBI 2H6L-26D1a3y7S,tHu2dy61in38Ma,laendRaHt.s26139: Repeated:Dose Dermal Toxicty DuPont.13852 INDIVIDUAL EDEMA AND ERYTHEMA SCORES EXPLANATORY NOTES DRAIZE* SCALE FOR SCORING SKIN IRRITATION Evaluation of Skin Reactions Score Erythema and eschar formation: EE 1 `Well-defined erythema. A --------------------. 2 MOGC10TSBEVETE EYEE rrr 3 Severe erythema(beetredness)to slight eschar formation (injuries in depth)........ 4 Edema formation: Veryslightedema (barely PErcepible) .........ourvevrvmonmsmrssesrns 1 ~ Slight edema (edges ofareawell defbiydnefeinidte raising)... 2 Moderate edema (rised approXimately 1.0 MID) evo 3 Severe edema (raisedmorethan 1.0mm extendingbeyondtheareaofexposure). 4 a EDdiiatosr,ial.CHo,mm"iDteermeoalfTthoexicAistsyo.c"iation ofFoodand DrogOfficials ofthe United Stats, Aus, Texas, 1T95h9e, pp. 4659. = Company Sanitized. Does not contain TSCA GBI oy. gi ii b2;X Bop? 32 13 & go seems 38 Si py 2oeaseaana giz Bo. eens ~ EE Ii ,, coeeomee =z i 22 | ig. eee I ii 2 gq Tomememine i iz g& iy 3EEg, 4: ~~ g24dl:4 iiz: fo i: of ii! i remem ceeccocens cspsa3s3sssssssssess . 5 ! Company Santzad. Doss notcontain CA GBI ~3 iis p50 38 18 iF fl. i i: coe eessseence eecocsccce i 2 Fd :2gl:Bjiazz I iz ii cocccccccs eeecccone i i: 2i 3 #: siessseese i: li EE ~332l35 : sazssssans . % CompanySaniized Doesnot conTtSaCAiGanll ~ EE i 22 i ~| s| i $3 5 & 3, zl =sZs|. ~~24: iz i5 ccccscose. iE . iz : 2# 5S3i3d3s3h3sRiEaanss # CompanySutzad. Dnoe constain 5A GBI --_ HH gz gis oi HH i: E(giz ~ il: Li y, g| i i i` i 32 i is eeeeenees eseo coosssscce 3 ii 5,iq:eo 3 . Fg 33 cecoscesce ~ Hi { azazasnen * CompanySanz.Gosnotconain TSAG1 ~4 8) il: as 2 ii cosccseccscs 22 [8 eeseomeee iF Is -- gai _ Pro eee Eid Fi or ememenen 5 32& P| oir eee i 3d 1 5 3g gEI gs HE ~ ial: 32 i: . Ln cecccecsce dF 1G g i samzssases . = CompanySanitzd.Doss ot conTtSaCAiCenl ~~ if i ~| i 3 =| i 3 i3 i i: : i: 2B5s8. 23% sa ~ 2 fd8l%3 iz, 2 13:7 2& = i$f ssumzEzRsasasnzaasss CompanySaiizad.Doesnot contTSCaAiCBnI gi: it ii z2 ccesccccos i: : i: JT HE _I : Lid: i i: i i: : i: in, 1: EEE 2 eeoonns Company Sate. oss econT50AG1 ~~ iigl: ois EE IN 2a FI 8a pr eeseeecees 8& fg oooooncoee i LE _ Fre cecccocene 1:33% 0 ceccconnoe igz| 1:13g7r eee 3 ;g i: 5 gr eeseecsees 2 E8E2 4 23 o g5; 32 i:2 svesvasnes dz 4 sevbeovues ~zd|i i Zz3333RE83 ) =5 Gompany Saitzed. Doss otcontTSaCAiCant ~~ HE ii a i i ~| ! g| fl 3 3 : & i. EE gy Bir 52 ~5E5&l]% i i {5 ceeeseecee Ld 7 seeesesses EI 3 cccscsssce 54 gr ceecoseens fF = 4 s5a3p3v3s3u3n8s3e3s3 %: `CompanySanitized. Does not contain TSCA Gal i: ~ gl | Hoa Hos 32 [2 32 fo 3i i . i i: eeeecen meemeeeens oeemeenees svonsnpnne Lys oom : Typ cee 5 PC ; iz gu meemeenees 4 33 24 o | sesssececs iH5,3 i.2 ~32g43s i: sppzszeane . Company Saniized Dossnot contain TSCA Gal ~~ EE, ios oi; i: [3 semeeneens F r3 e& comennenn jaf ~ ih: 1foso eecoooeens 3 if i "li : gro ois Ln eeccscsces 4I3g2, ir,2 ~zgl4i4 iFsR uszE sssE ssa . = CompanySante. Bos ot conan1564 0 TM 3g 3 i i --_ i HEI i i: | g 1F 7 SE ~3E glE : igs iPsL szzs-- smmse A CompanySates. Dos rtcontainTSOAGOI ~g Be ois Hopis:. cecccccone ii i - eccccccsco FE. eececcones 110 ~ j15f} i i " ceccscoscs ih Dp. i i: eee eecccoocoe fo. ceecececee gl i Bgll.y RHE 5. osnsomsons 1i: sszzaznnss A : Company Sanitized. Doesnot contain TSCA CBI iEB23 Leeann ii: ii ~ i 2 32 3i 5 I3 g 8;23. S3Ess gEgH: tik iz fs 5 $12 182 Fie iE $ii $i7z flr Hh fo if fz cocceccoss cococcocee ccomeconne ccccccccen ceccoconnn eccocccnce eecococnce fo o eccccccace : if i a7 eccccccnes sB@p o&z s33sgsmEes : * ! `CompanySanitized. Does notcontain TSCA CBI -- HE 35s [1 i 4 i ~: i : i833 & i 3 dSEp: E2r:FE ~ 8&2 i 5 eesecccces LiF fu weemeccees Ba gg eecesseses 2E fs7,Eoeccoceoces i; 1 3383885383 = Company Sanitzed. Donotscontsain TSCA G81 --~ i3s I ~ .| i 1 $ : 1:8 i i. ii: I, iE :ih: 2 i. ia cocescccos cecoe sescccccss & Ls Zi: EH 5 HE ~ 833 1F.E coosocees - fio: f 3 i o I ecccccccco i sazsssasas , # Company Saized Donotsconstain TSCA CBI ~ ol i: lis % i oid I: sessscsses 1 ig sevesesces 3: $i 2HE3Y 1: $1: ceoccceces cccccccoce ~~ 1ti8f fix sesossveve | $5% : i i2 cccoccccos EN 2 {2 cccccssces 5 2 iz ig. EEHEEHE EEE fz weeeseeess iE - Piro. i 2 eoscsecccos fSoioecocccccos i 3333Esasas } - n CompanySantzsd. Doesnot conTtSaCAiGBnI ~ ti ii ) i --~ 3 io2 i: i 2z: 4 sereesssce 3 i k Jr eeeemeeens &gSy EZ 6 teoesscese i8: Pi:f; S25 tik 7 i ssEiae3aemnseszsEsz 3 . CompanySaitzed. Dossno continTSCA Ce! ~~ gl BE go FL i i2 EE ecccceces cocessscece | iz i JE ecccscocce jas Fi. cescccance ~ 18} :Fi E3l 3fi. ceeeeceee- 1 Bi 3i f8o3 g if EEI ccoeoescnn ~EEF Ts ee 3 i Company Saniizsd Doss not conTtSCaAiGBnI --_ EM H3|3E2 i is $i ii1iaE 15i33z eeccoccnas cocccconas ii ii2 i3 eccccccoss --~ 2i:is3 % Eg2l| fi4p8r eeeceoen: i 2 3 iE g Hd ) Ey HE 25i]ad {i ss3uznapspssaisnenss Company Saniizd. Does not contain TSCA Ca1 ~~ i: 3 8 a i - 3 i z i: & g : 15 ecccconces gi i3 f 5 fa eeecccoces % Pi iy {1 ecccccocan BH. if 8g32]%3 -3: z eocccconen SEY EEEpaSO d --EidH lg EsyR mzosE ssEaHs 5 CompanySaritizad.Doss notcontTSaCAiCanll --_ 32 HI ii ii Lif jac ~ 183 gFZzl| i3 i8. Hoof cecoconeee [I % 3g gis EEERMHE gH: ig: if f% 3 coccnccces 5% spazssaas: : i : | CompanySaniized Does no containTSCAGal ~ El: L 2 E , FE i: 5: paEsN Fis ~ 3i: 7 Fre gI]| fig5.% Book a Zz ccccccscen cocooooeee cecoseeces 5 82 3Hl. SEH =F: ~33|3 i: secsccccce ii ii:i. pa eecomecces 2: : i sspzszsesz 2 [ST S---- ~~ 3 i i --~ 3: 3 $ ii i fr eeeecceees 3 LE i&s id fa I5 FRizR F2EE3F:8 RfgAii --zSdlH eeeeceeees coescccoes sEsEpEezEsssssEzeaRs %& `Company Sanitzed. Doesnot containTSCA CBI --_ Dl2H82uD61ao3y7u,SHyu-do2y6iM1n3i8a,eearndRsaHs-ss26139: RepeatedDose Dermal Taiciy DDuupwoenn1s38m82 ~ APPENDIX F Piya Report -_-- Toi Company Sanitized. Does not contain TSCA CBI ~~ Z0 2DH6-o:2DS6a1ye3Sd7tu,ydyHp-i2M6n1M3b5i,leaenRdRaeFt-ss26139: Repested-Dose Dermal Toxicity DDuuponte138s582 STUDYTITLE 26157, H2S138,aad 26139: RepeteRaDosseDeclToriity28DaySyin Mle: "DATAREQUIREMENTS Anilyical MethodRequire STUDYDIRECTOR Carl Finlay ANALPHYASETCOIMPCLETAEDOLN March 10,2004 --~ 'EERFORMINGLABORATORY . 30B5x8RpemsReearscchaDrnihve SuPheoCneo:ll81g4e.,2P7A2.110633901 STUDY SPONSOR EduPond Nem2o0u.rBsonxd5C0ompany(DuPont) Newark, DE 197160050 USA EROMECT `Sa pon SudyNo.] DaPoni-13852 Toul Pages: 63 --_~ - Te Company Sanitized. Does not contain TSCA CBI --_ H252:60157S,t5y.26i13M,ilaenRd5a.s26136: RepeDoasetDeermd Txiiy Duronc13882 Somsy vf 00D LABORATORY PRACTICE COMPLIANCE STATEMEN] DcoEosmxeppDienrScmuavdliNThoUubSoI cEP2A6TDSRnCyAS(s 10yCFiRn.p"V4ia2tl6e19R527aG,to6"o1wd3eL8si,bcoo2rdtnro2yc6P1ira3dc9to:DSuRekapocse 15h9ri7sc)h.o iebcloesdn tion EvitlNt hOEyVCDofAo rocSIocfcGCoofdoHcLabtEosntodMyPraOsuim1s(osl.rowi:dTs cO1h.oTanormenfwroshyveo aRmaechMestwfoikiisebedoJytR n5%monaE tn.dyToertI si ewitpno, ucv ihivcis bay problemsobserved.Thein-lsbsodicfflserveas a process-basedinspection ~~ = `ExygenResearch SCeoyrDiyor (i 5 e Bae lo Beueater 200 r Soomn R= erssive [r-- Bue zara -- ------------------T--e--------------esm a CompanySanitized. Does notcontainTSCA Gall ~ 22506,1St5y7n5i220d65216139: epDoessDeemat Tvs Dupes Er `QUALITY ASSURANCE STATEMENT Di eyriim ngRToposiEetsom2eQRtyySroscyraiSonnMaisde3eaO0vp.iieATdBpSoeeenssw,iyeb1veN5So,onyRePfrorocco,DiREP1os9 SoBnraeeitLoomnarisStas A obsom eos 8 3 ae l Due e Deporetcebevs gee S Sansto DateReported: E rj foenrE = - domA pruame om ons ow om SRreieneer ome ooo ome ome Spioviasn (holt `QualityAssurance Autor =3 /rolo Cm*EEmxeyibgeeanooeQeAioho bsnetrvvveeisdaiStnin-nloaobeprhtotctenv dps areefsdocrfosv ytguudy Q g rgP d s thi e abovee dcateo.eTnhmois Spates rerun ~ ee ormis -- e ------t CompanySaitesd. Docs nocontSaCAiCn81 ~ 1282D61a3y7S,u1d2y61i35M,laendRaHt-s26139: Repested-Dose Dermal Tosi Dupo 13882 RN ad `CERTIFOFIACUTAHETNTIICOITNY The isrepo a ffoo Exypdeyn,StayNumberMER i reendcomplete repressionof Smitty SB0u3gRReeseaurDsive SateCmallie sPA 6501 Pcp vero, Beye: EEpEpes RosenA ---- ae ExyenReFuslMcimhe: ~ Vi Faieny VEicregPorRoassaech = ht StudyDict,DuPont: CDuoeoste bBaeac oy SponsorRepresents, Dupre: S Dopo e Bopp React BP us T totes -- --- Te Company Saniized. Does not contain TSCA CBI mLvoinFdipa,iYecrn2197TReetODeTDeTey ppeeiie EaNs o IyE cT one soerrit Tt [IEXDYGEENNSTTUIDYFICATION Sk ee TET Soh EXYGENSTUDYNUMBER: i orn sa mame: A -- FR E4 sieseE ursy ~ momen c=nr PASAT HEpiteeale, a pre H r sDeypemerr . v.e R oapw rates om _-- ~ 2266-1De5y7S,t5.y2i6n13M,ilaeoRdat26135: RepDoeseDaetTeoridc DuPenc13s82 Ex styoSP [PROJECT PERSONNEL ohemEStxudpyDorRocrafowe psrohjecoDtoihtvwoissCapsFyf.eTetlylin pene Name | PutComely Bi Docs Karn Rika Mak ecy ShavnRoth Tite TehmalLadions Seni Seni sos SampoCurcctsn -- --_ --_-- [--. esata `Company Sanitized. DoesnotcontainTSCA Cal 526261135,5an 726,135;ReDepDermealTodi ~ 28-Day Study in Male Rats . DuPont-13882 ------1< TAOFB COL NTEE NTS Be 00DLABORATORYPRACTICE CoMpLIANGESTATRVERT "3 Be -------- 500DEREENSCECMAORTFEARIAIAPVL.RTEALISOTAGN PE Ster ------------ 63Demsp n So pinCot si la 6.6 QuananidEtXEDaIetCAi ICHoEONn cvs 13. 50CIRNOTNETAOGNFCREHSITEHDTAATTYVAAYm RAVEAr CTEDr TH GOoALITYOF 1g 175 RETOFEBHNAATN SIAMPLOESN LI OFTS ABLT ES TUL SommeofA RtPl) c ConeSans. B1e TL SumryofRvs MIR)iRtPloSnes 18 TableIIL SummaryofResidueFoundforSMMb)inRatPlasmaSamples. 1 Bor et ~ -- netaes Company Sais. Doss no contain TSCA C1 ~~ 2$82-6D1a5y7,Sedy6i1n36i,amldRaHs26139: Repesed Dose Dermal Toxicity Dupon13552 pr LIFSIT OGFURES nas FFiggor?1e. TCyS pricmatlL CogamlAiCurrAvsefotrYiIoCPnaSboduigAloin 2 107001 Fipae. CSlraogaiaoglan-- Ropi-- ngCo-- olRt--sus-- (oI--vic.-- Fig. ComomstogranReprscniogCoolRaPlasFatified 10 vith - 5rg/oL.ofSE---- Figues. C<oSrnogmmoigoarn fupins 1, ~~ LIASPTPOFENDICES Bu AppendiAx StudyProtocolDuPo-13882(BxygenSty NoMand. APPEOdIXS DAescanyinaMieobnofgQ EXHA0U US176RoE isin2E . MadN oASscS irsatothe -- sores -- Te Company Saritized.Does notcontTSaCAiCnBI --_ 2526D1e5y7,S 72inM6y lean1Rdat3s261,39: Reps DoseDermalTonic Dupone 13882 Bsoe yogs E 10 SUMMARY s`cEoxoyepdeinnRges1eaprrcohto(cBoxlyDgaeFn)ons-m1a3ly8a5s2d(sAapmppelnedsoixfAra)tpmliangstmhafeoanrarleystiidcuaelmsoeft(hoNd in ---- (Apps "he lof quanfc ismhi 10 ob, which vascidEy oe hosvi sd0n 08.277 Residesof Re ss spies ged rom < 0.0 gb 20pp. "Tehearveraigerecovery +standarddeviationfolSNNNNR fortifiedratplastasamples was. 2.0 OBJECTIVE Thebjcive oftis clsh asfo nas pessamples recied DI emianof Scr LEMrOiNSs ~ 30INTRODUCTION his ep deals rssof ismsof otplc espe x PFOAwo anhaeiliseiecnad!ymwpeoachnoid15t52d,Tahneos ver 1,2y 00,vwiah Taheyse a1y3.d20i0n,oansdd ighneedspircoals mi te we iyn 5.3000 4.0 TESTSYSTEM. : TTTeooeconnnotiouleJsmttepolmssD0aa6b2neo0dy0of0onAc1LoGsDnLdNpSs,acmFpvloeesyrardlxogbhs oamtebysaEcxopymsgoewfepriaeendcnseind5eps ndpre ot os2 20) Si uerpiee lowgsinttwidghityowf Sclaosrtady ftoswinl baonKbootfoaogdienntReerschandc3ae hd on BoeRee safes -- ----------Te-- s -- a-- --e-- se -- t `Company Sanitized. DonotecontsainTSCA CBI --~ 2256:10357,StHud2y6i1n3M,ilaendRaHt-e26139: Repent Dose Der Toxiity DuPone 2852 Ecypen Study No GEN 50REFERENCEMATERIAL ThVP eiccy05t, 200se 5 oomcCS1r2UMa8-o 5P0hwSaerrviicevr eidtoCOyR i oincFeeGvya4l2a 03,Sa03n0d35ao)0n0 Som SoTohneavrpalvlae nsodrman5 foSrhthpe eee cicloni] asialbelwows, rThdo syooan Compt om lade Pei EuoioDu | se5xs oouess hooetss ceoAD i: cxir) ssunita ven --~ - ji CMoomncainvaemgen = EyeReh rae 05863 emerge pp e---- rere Company Saniized. Does not contain TSCA Call ~ 0 e2H8DDua2yoSwt6yud2iy6in11n3MM5au,l3aenRRdas7F-ss26,139: RepestDeentaDTooisctey Doupwonte138s82 Syioms ID 60DESCORFAINALPYTTICAILMEOTHNOD 1Extraction Procedure 1. 2 MAeidnhsmaooe0h1 mesliooftsi,emlcpoic evi4t,o 21m6lvops r ed1oi w0acnoirn ndgss10we 0e05s(us nfly. 3. Covonnonrigngffoofrror-F11r0ismcittmieo,sn vue to = 149000 mde en cxeacionvlan 00BL. 5 Rye is in nyLONSAS. 2PreparationofSsndards odFortieationSoluons coTp(nhrceeasptaocrctkoionsfnooaS:rnoeuifnaimt1)0eoiruiong1n7,.b2doa0bf0ynW,.a&s1Tsoh1vvimHaoosecspekrmetsopaiimmniuoosnflSylp10oi10eobpmnmbptemr1.f1bC,tybR20sr5e,nedaaagr+d s`Sioaoliiopnn roafdaGbEi1nEg6inmgof0heivasiuLmnwdaoespd(tcoear4ree0tdiendbsysnipiglye.103mAL1ofrpenl ds.Aoifcvosrshieeassiiioonns ~ prominent `solutionof "CHEMEwsspreparedbytaking1.0mLofthestockandbringingthe miatesr. Thssoloswer td forty he plsaad vaca union Asetofstandardsconzaining MMwith internalstandardswaspreparedbydilutionof the100 ug/ml. SERbion andthe1.0 pg/L. "CMM solutioninthe following. TREC: Vow DRED FOoEo a 101050 aito 10000 ao1n o 0`iv5orlu3nm.eo1f0onghilevy1e a0conmce.ntrCationof 0.l00i5ogn/mwaosfdPdCiRoetom seaicnhg `Taohfmecpliceasnb.ctTiohoencssremsdcciknddssaedgra tosrsslstyoasdtgshsOchenacedcs dcooxpngofodm,cdriovmnihsnuohce odeysGcoydry,Qin oUwn.gTo(rics ofthSani woe xin Bop React renoa --_ - = Gompany Sanitzed. Doss not contain TSCA Cal -- H28LD-2Du6a1Sy37eS,dt2av6yi1in3o8MM,aealeenRdratsFs-s26139:Repestod-Dose Demal Toxicity wDuopown13882 ExpSod NoSD FoO rifcaStCaorn VFiatohni) VCoowlm Sample mt) Soluion goeorl) To oT oolot o1 x00 0 0a11 1 0 ] ot ECranedd C`aSlalnctdiaodn g1b0 52 010 sToahluseicroxnetiapcntrdobnrbisynlgtiaunkgoitnnhwe0ev5snoprLneopfa0rtehdob1.y100a0pkmilln.g.wi0t"5hCsRacELoonfctese.oT1oo0ntynGgdub.irin"ngsOiniRtoNhneS lime5p 0 100mL,with5050metho biTnehroutnodecknstofaendra(irw4ddoalg2uatisCoen)owshcetfnaowtofintorsx.rfeDposotsiasoamnonfdeseaarnndolalruttdriponeaapwaieeitriosooonrnned 63Chromatography ~ oQTfuhtaheteitbeLen0stiiQoosnnttaoinfdmaeroQtf)Rin.twhacs oser-cos2m.pa0lmspihnso.cbwoirytemhspnaoonldiisgngasioicntaghteiisncntrleocseprirgnypLieCnsMiS(<Ms0S.%. ATnstrumeatSeattvity "0Top.mastamountofQBcjceddungthechrocstoprphic wassilent 0 65Descipion of InsiramentsdOperatingConditions suAiPsiBiSocnieaxnLdCpMroSceIsMsiSngcworrplpdtcor@HeoswiengPAapcakardF1.P2LsCofstys.m wis ied. Data `Deaid eranconditions =Bed elo: MIamsriSep:ec: CSoofmtpwuatreer: HPLC: TSPuCBItSEoCXlIToEuoXrASbPporLky4ont0S0ep0paBeyrLiaiqeui=do3I5t0mMmcCsiwioAolnhnNs2tlyeasc1tLsinn DPeElSlcOipetxipAlenxdGyX:1V1eDsion12 BewicPac(7k)Saesr11d00 EaReurh Pei20r6s --~ -_-- Te `CompanySaniized. DoesnotcontaTSiCnA CBI ~~ --~ . . 2H8L-2D6a1y57S, uB2d61in38e M,alaende RoHt-s26139: Repeated-Dose Dermal Toxicity DDwuPoomnta-1s38m82 ESv ud No:a 008405 HBPPVQaucauuPmaDpegaser EEPPACuocliunmiaeCcoomrpartnest HCFPoiLleoCrmCCaoTrleviumdmpg:e:(sG3e2n0KeesCyissoCnyeGHaynpeesrCahr rinotemma,texo2it.ig1ngrmpusamp5p0.mhsy,4, MoMbiloePPhabasse(i(80)1:Ml2emeMneaA!mmoniomAccainwate | Dm 30 %A SB Hex(03lmin 03 337s 70 00 11000 0 100 0033 0s 05 @ 00335 Bjecson Val: no3S4L "" 0033 Tons monoret: Amite NeMgoudieveTmos4in 1o3nM3a6n5itond Neguive 4153370 | 64QuantaaidExtamapletCeicuoltinon pFeivaxewkemirigechertowilnagtseomsfoetfshasmreapdtloensodarctlhleeibpraeantadoknaarseacanufdreivrcedwnwlsesrgteaeadjeaercsdtpeedebanyoHatorhecesvLerCreop-reMshseSiro.n osTinhogfe tebhqeeuficovolllnoecwnei)nnsagoaefiqtuowanatrioeofnssyo:atleyme.iTcohnecernetirdtcioonnocfenterraadfoonrMIuswiansg dAcesirm1a2nrcoodr `etEgqrouaeotsiifoaonnnap1lawyrataesmpesetaeekdrst)ogrescnatelocruailttaeetdecbtnyhaelhmetoaAnadnitndyopfeasnoaafltywrtaeeraf:)uopsrniodng(griahme.9stbaonrdanrgd rvba(seidvonr ABnaailoy no1u;nd(pb) = Amsekacspak) ere cep x I con. fl xDF BrynReseach Pus130063 -_-- `Company Sanitized. Does not contain TSCA CBI ~ M2Hb526Dw1a3oy7eS,u2wd6ym1i3in8Me,ilRaennRadss26139: RepesedDose Dermal Toxicky oDuwpoe13s882 `ESxudyyNoyen Foedaompc lesfrl hiepwriettoe owvseamosof yep boction,Equation 2was RBeommy,(6)= `aieo"nmdopbt).ossAwuede7o35d) i son Gs x 100 FSokrlaadgstoacmupclaefortispewrithkrnove:ostofsypoe 0 xis,Eqn RBecoavenryn)= . `Anatom"Aemo(uontRpa)y.sAwaesGopn) i ple x 100 CfAOnc=mp-- of calceinving rcits1l0oblilos:GERtpsssampleExypen fBF roomGnemE ) 2Sabeaanger ~~ sGinelgeen er) =DZoom1 oss fisboaededtGvoitneog)l = 10 FAroomuiquyatfoonGmo1b:d) = [NOTItONs =004SS] x41671 = soso FRrRoemoquvayton 2 = O8S3mhz0lxi0 - om Nmoyt:bTohigslcaympfoaceaifoonnvoeavsdionce ingroundeRdaAbWDeArTAs.nd hector EpReact Pett PN -_-- Te `CompanySanized. DoesnotcontainTSCA CB _ H0 D2162o6DS1a3ye7b,Suv2diyio6nMMia1leen3rdRaeHt.5es261,39: Repested-DoseDermalToxicity oDuwpone138s82 Bsa uiyNm oSEaD 7.0 EXPERIMENTALDESIGN Ecaocknhndoniwyocfao3!engssetewtrai,tkcax.nmcineelddscotlinxiecnogruir0o,dtM cwhooAkbnoown,N <TomeycraCtoEnD O,?30fipn=eesdi sump, ndon ldsulexact epic. 80 RESULTS : The oundnhconorpassspcseitdfo Table. iPnlTabe leIpLlTe ehweesse8a9g%4sp11e18n. roeveys 2sunet sdtes in fe r ii noot Redsiiduvesiofdleisnortth hraWtptMmIsatmphleesrrpanlgesdfrsoamm<pl1e0.s0papbgi0v2en3 fngTba.bleII A pis casino Fo ndrepsetativchromogeinn Figures 1-5. --_ 9 CI`QIURALN ICTYT OURTHE MATSG MAYTRHAOAVI FETANHT FEFDC EACYTTEEADTSHE her s20 kno tacrtBev fst hesulto pityof oe as. 100CONCLUSIONS The pessponwersslsyedscorn(0ood QR -- 11.0 RETE OFDNATT AANIDSAOMPLNES iWmhlembnehehifpopiesad.re1poharecttsspccooomrppl.eeTto,hfiacdoocpwedmattp,acpiaedwdeelcag2c5oy3rsSepgedncbiyeEcroospypdonftRemscSeorsmt Remmsliceuneosfealpceivnaedfaortcatihcegtpse)caofdyosfinisdpbcserpoiwscpaioa,4nw0illCbFsRPiano793 RBeenrdn EeResch tse --_ - TTT `CompanySanitized. DoesnotconTtSaCAi0n81 = mT 5L p2g6s157n 15262110I 0,: epDo DsomE Tc N posn s: soso EY -- ------ --_--" ~ Company Santis. Doss ot amTaSOAnCot ~~ AT 2o8-yD1a2yi)S1teu3d6yr1i5ni5M,ailmeitRa1ets2I 65 ReepaTT ts Y ease DuPont-13882 sm SY Table. Summaryofl(ppb)inRatPlas ControlSamples e So SScoooFnmrAentrs an -pi*sr-- 10err m0 --_ ST I CompanySante. boo rtconTss i co ~ Eo2H82u.6Di1a5ym7,Sbo5y2ye6i1nM3Mu,ite1e0rRaHst-s26133: Repeat Doss Dermal Toxiiy oDwupeou1n38s52 EvenstyNoGY TableII. SSuammpmlaersyofRecoveries {lil nRat P) lasma [year a: viet [er r-- =@ - wow =3 Toa 05 =LabCoontueSrie Soe eh --_ - Ps sor) ms Company Sanitized. Dosnot contain TSCA CB1 /_ B2o 6n13,bt a12y6158h, mtda1ee12619: T Repent P Doe DT ematTosi efoss omyEY TobeIL. SummaryofRedo Found orSeinRtPlaca T--e2z Samples. p9--woHn , -2z2 o=peuer =-= - eoBBHeHo 2Eo" &==5 z=== E=25S _ z==3 5a4 Eo=feyw b=2i = ===z ==== =o=n =2== E=== 2=i=n ==== w=2= Sones --_-- --_ -_-- Company Saiz. oesnot contSOaAiGBnI ~ EmEEm, eLT: Bp Dor Tory pone ms --_ -- J. ~ CompanySts. Oo romaSoiAGno - E 26137,r 52613r 5, 26139: Repent Doe Di Tact Drm xensoy voSR Figure. Typical Calibration CuorQvRe A ein pot 1570 mn J PrErRR LESE ATm TIE EReE ETR Es mess retin --Ser seeeieeemopegsrp eeeeeeeeeeee CompanySantas. Doesnotcontain 750AGBH SO AT Soniorsinbty ~~ 28-Day Study in Male Rats DuPont-13882 oreo NEw) 2) Nu10ppb with ng of"OY fmm | sa | =| | | | ~ EE EE Lo : mara nt ~ Com Stnt Bose ~~ M0 E2b56-w1D3as7ye,Siu2dy6i1i3nMM8l,iaeenRRdaetss2.6139: Repeted-Deorse Tocicty oDvwpence138s82 ---- Figure3. RepreConstreolRnattPliasmnafgor | SEER == | FE&- 2 Birds I I B= it: | =f F E3 fn CLI MY | _ W. =a =o | EE E=REut == | Bom Reas ~ - Pnoa CompanySanitized. Dos not containTSCA Call - Z0 D2H2y061sD3a,S i1.M26i1dn5M5ey l,eR20Rs5a2te6e135: Reposted Dos Dest Toric oDwoneissse2 re] Figured. ChroReprmesentaingCtontroolRagt lramaaFortimfied r SE E=o Elid | | || ~~ =i=] I | B= | Spears fe. Company Sanz. Does not contain TSCA Cat FigurSe. Chromatogram || =| i Fo i J-- | | | | --_ 2H826D1a3y7S,u1.d26i1n3Me 8i,laene dRaHt-s26139: Repestd-Dose Dermal Toxicity bDuwronte138m82 -------- Study Protocol DuPont-13882 (Exygen Study No. Sly and Amendment and Deviation Boro Resch Pesta -Y CompanySanitized. Doss notcontainTSCA CBI --~ E261n22t613a,t1e04s26135: Repetto De Toit Durisssy : momo ER 1i | od | Pi odi ~~ Sewn FH26137, 26"11n2d310-821n,3:dReekRpDaoeseeDaeatlTeoidt | CoE ! -- | : ii}f || ttst tsSmite | Eiypen Research. - - * } Page270063 [ES ---- ~ ZD0 2552yD6s1a3yu7,Shu5y2dn6i1ynM35Mi,ieeanRRdas2ts6s139: RepetedDoss Dermal Toicky ouwpeons13882 : omy(EN pa ane ---- boven i ~ Tastsorcovravts. | Lo . i|1 osewrmomonposvomnewmdwivT.. ay cf rn -------------- !ii i !| P somae --------T-- T f B&BDhmaemep Td | i i i BGFBAFBAe mmemneG1 op Bey t !i -- i| K Cy lap be -- ee e ------ ---- m iK P Romee m y -------------- |i, i! ssf aarmeemr e or au --s -- Te T-- T , -- | | sara) ! 2, - eee ---- EinNiet }| hs } Pesos - `Company Saniized.Doesnotcontain TSCA C81 ~~ 2582-6D1a5y7S,tu5d2y6i1nM3a,l0eR5a1t2s6155 ReDopssDtea Toss DuPont-13882 sorve:(eEsR | Emmesen. . I {i[0 Doromcmorcot13 Ra can EERE mtsofmlaie:Th eatofGi shadywil be gn i cpa 0rmbt lo : | p|o pf E ptE e torR tRsesous ] |, | |Dp ee tyBt ra estes Cmmhe etepe po |i ~ - fpetey RS ilbeoctd lL fr thdBovina San,1. /i |i1 RE EaEGbULerATPORaeYCOSMsaPLtIsA,NeCvEikccoema swi sSE cmon R i = = | EE to Ee |! ! EigenResearch i oy Page29063 GompanySanlzad, Doesnot contSaGAiGont ~ ET EF oytmwemvT ieeis -- ET p-- ees | Arsenio _ iD: eenrti: _ . |; {;| wLP A Fl H a ! m hmr=. Em me mma em-- EEE BT ! mEtehs va b --_ ---- ---- Themac resuppliedbyth oo ndasiger oredtee niquec HaskellLabboroscryy| it B TeSpecer FEYale OLCOEDSBtmrwill obi rmChe ive abn,Jo. The pe as e Cr CCEORSDISBhsbo do ef tespss it i ? | i3 SHMmtE:oe"co i s--vt=o--erc--p simi !;|| _ he BayeReseach Page30063 Company Siz.Doesnt onan Tach G1 ~ 2152.6D1ay37S,oF-y26i1n3M6i,s0eR4atHs-2.6139: RepostedDose Dermal Toxickty Duponc13882 . Eero(ID re | E B ncoa ts emie emi .oven i. S ttrteityBoma oe 0 ioe : ; Sp Al willm bepros videdtrywera bin.ARntswillbs ne lodPME Nuon nernaion, ii i: rte fe ktLibrioraltbr efsad bt0en ieseiatid i pn } i + FLee m nye fe rdp te ; "Seis Sm fai odo en te ee ii frm mei e eee s e mmi --- ; nn Thetnirmyadboealtsancdcoovie,vmmDrtealrocerieringprpopaliydioentbybey hse enBdiyng80 ii |J i|1 7 t rortr sttsia ome ettsmte iiie i D r etm grtbyt eegtyfeemn en !i L cedTt drerosidty ig ed ctBtwpet LL fii,meerr er eeam eoy es i : _-- } ERs per = --_-- CompanySaniized. Doosnot conTtSaCAi0n81 -- T r512y61es57w,v5y26e1i2M0,imedr12e613: eT pDee r Te ox Y Dwupees13w2 - Saves ND -- . |P EE amsT me emeen ese rese eefeeem | EXERRE | , rE onls soimsEERnSetEtteRseEcReuee | o 5S3mee art oe ta atta- p ; | EBFrEEaEiTRheEnto spp eet ety e !i: -- ~~ freon | | jEF E o-- EE r REa-- e2ESaose R-- eRtatnEt r vR-- es RmepLsot,TIh EigReer,Lwe . | | IIDeElEl o EeEdmo imng emstr amasido.Thseieeeacehterniin,l Totem G. ModyWeignn ett, : it } le e os | dopants - u } neo ~. --_-- CompanySanitzad. Doos notcontTSaCAiGni ~ Ele Dron os e e1 m 1320r 9pt Sr ety Sou : I Iriee t { Themmo of food condby cach a ilbndtm wekly byweighing exchfod: i , |R 4E EehecEniEameam eymfodciC yu ibeedle ! breotesi i I So BEtSEe t E )emmhmta mevmrmcefnietmtgatrns. | ~ | ncoersme esisve | | E T EE FEEE mi m iTem e mmer emr rmiy mm.m meee i| | | Emenee : !{ s| BiypenReseach Page 330663 CompanySn, Gee otcoTrSGnCat 261261338,an726,133; RepDoeseDaeatlTeoidt . P---------- | oda ; Ss r mn m msi e ee + bicep : { t TS -- e vLing renhme tsibimi:: ; i | wii eeet !{ [oe mr . !| Sn Jmi etn arent. 1 8Leu mttttr y tyi o it sreti e ,uy ! ~ iif E S e E Ek E o Te T e n hea Tea B i SSe : i |Po r S tm abhr e ep ie i Sy eih ns { RN : |Po mE t de a mre i | Arteta i *: Bop rs estas --_ --_-- CompanySanitized. Dows ot conTtSCaAiGBnI --~ E5256a1y7,Se52y6138,thnd12e6139; RepDosoeDsermtTeosds pr . eens GY a : -- || iIE e E rneT--T ------ . ; | fee a { { . | Ea F S r eoea mcneg m eyee mEse ! | 68 ty te tt is rg yet ST re necessarybythesdimctorofpadbaiogi. ] |i -- i : { i i | Soe _-- . he } _ a nesses CompanySaniizad. Doosnot contTiSCnA Cai --_ 2826D137S, 2yi6nMi1l2e03Rdt48s261,3: RepDoesDaermtalTeoxidc Duran 13882 ) z sorsasos oR E J n bw | staa msTicALAAL--YSS--S -- : ii |[o= e TCe Ti Jll -- fa a] : | ERE [a Tam[may [[earre ; i i CY = [ECorveer | el e [e tt e i [I eran | -~ | f Perie e a e -- e it tt ! E ever or ; E T E Eto T eaen scaraerimant e |! . Oftemebowidllbsesued,ifapecprine, he timeofanalysis. fea!methodswed. { : : sarymomo 1 Samir Si G2e0o8d0bovxeaiekp aspingc prbiecaedksui esWcil.lbTeorastviionsdi10ncviodtcaontamiontion boefwhertawthsebwbtoanncien.g i|i i a3 SnRh Pts --_-- Company Sanitzed.DossntconTtSaCAiCBnI ~ 3F5aLS2o2y61638i,l1aenRd17s.26,139 ReDposDoocssToreic Duran 13582 . smurf or B i Eor rasearriny .oe ! | pre hm toy ; nt i . SrASTREET | meee ts | Eh ~ | i | ; Ecypem Research _ _-- nn i Page370063 Goma Santzed.Doesnot contain TSCA Cal --- B2b552y610s37wS,h5y2e61vm3t8,eeanrdas2s613: RepoDosetDoerd Toy 07 Dpuwrwa13s36e2 : SomsicAY RS pS o meEsts et Pm ; B ; 1 elebs .B2 Brtoer Tty { i{ E SaeR eSah StudyinMleRats.Vnpubiisbod por,DaPocs 11763. - te : f5 SE +SCDeEcealToxticr ity (e AUG-1998).i R ne s~ taten tt ! ` 1 So D ONp md.st.ef1. ptieodg e meAetse,2ee4 taimn nt beet i. |i ~ Lm 0 tnt ye nssrymd ! : I 0Sr ustics 05B .OliVnR ,Aoo d)R,pA27C81-25692.c.Soe traete esdUt niversite yPn res,P"alobAY.e o2: nd | i IV hr ts edeiSneo sosa. aee rrp ren" ; T10e0 iy oStesrokre.reFeber 435. s _-- Simro - } J, _ -_-- Compan Saniizad.Does notcontin TSCA Gal S 057120n 5 4136159Rpee Tosi a eossyNY J A sn 1 5 os amin, J mn i ShadyDimer Cam Filey - {Umi.: hEipohesir.enees AnsocicPuibologyBrabaicn. Ger. Spi ni --ee---- : ; | ermine soso i : ~~ SebadidSoifics December22,2003 | i | | : --- `BaypenResearch | : | a. Page390163 ~ --_-------- Company ented avs corsaonna : | ~ D20 DK8:u2D6wa1y3o7S,wu2vdy6oi1MnM3uale5enk,RdastHss-26139: RepoDossetDeermdal Tovicky Doupwoe13s882 i. Lanmnun,ecs:et ek ey bin { TL sows i t PI Po. | | | || s : Lo ai doeatkh rian.n3 i i - { 2 | ma 5m - BiypenResearch : -- ii ae | Page400163 `CompanySanitized. Does notcontain TSCA CBI ~~ Z0 o2H8Ln:2D6ia1y5e7Sb,tHubd2y6M1in3l8M,aelaerndRsa2tes6139: Repeted-Dose Deena Toxic DwuPoent-s138w82 2msoy (I i ; E HOES 5a.I tE e Tm T e3 ee Cer { SecA : { | CE Pat 2 is thet } ! i Ua h tsi -- tt lS. | ~~ i i | i = moa - -t EpReseach . | : !I -. i } Pagedlof63 - Company Sanitized. Doss not contain TSCA C81 ~ E pene ete y pre : 4 Pi OR TL. = reoroeasemi I i hl enre ss { te \EeI evo veer \ |: : CEE [awexe lw rae = Ee T Zi Lots kW eeu. ! i 1 _- hel NOR i . - Ca i . VET i Expo Research Paged2of63 ~ EEo2w6u1s7e,Sp2oi61yM3i8p,etenrdas267 135, Reped Doe DealTToiYt pDeuraan 1s356e2 asuvso:QY Analytical Method{ WPMethod of Analysis for the DW etermE inatiE onionf R Serum bE y LC/MSG /MS" Bop tees - re ssares Company Sanitized. Does not contain TSCA C81 ~ amEAdIw,EenLieSns 7pe0te er oc osreaunsg EpsootyNo SY L i X\ = ee w-- s . = i | \ doks i| \\ + ic 1 NE\ Soy 8200 f; | | \ a\hr SE on { !{ ~ j aii, ! 1 = .= [E---- SET ms | , A TOTALNUMRERORPAGES =\ i:i Kemi i : Nei ] tats ~ --- CompanySates. Gosecon3A Go ~ 2F5LD26a1y57S,u2d6y1i3n8M,lendRa2s.619: RestedDose Del Tovey Duron 1352 mosDY { t MANAGEMENTAPPROVAL ~ . od ; FyL" y 5 | Bp . | g Emaee ! ~ | SShadteses gr=y ks Sve : BeRes - . | ren |i [ Company Saniized. Doesnot contain TSCA Cel --~ 2H826D1a3y7S,uKdy26i1n3M8,iaendRa5ts2.6139: RepestedDose Derma Tonic : Dupont13882 J | EE | i . TAOFBCONLTENETS {) BSErermeleEE -- |{| IP3EBeEo A NmSees I og e | FE E -- E BE ii ! 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Doesnotcontain TSCAC81 _ 2H82D6a13y7S,uBd2y6i1n3M,isaendRa1s2.6139: Repestd-Dose Dermal Toy Dupon.13s82 Emasuo: (I i| - -- - | 2 EXPERBENIAL COMPOUNDS 1 Dfeie I tie | 3 f -- --- -- i -- i | i | -:4 | aa Er Reh Pbeln | Pores Company Sanitized. Doesnotcontain TSCA CEI ~~ 12552D6a1y37S,uHd-2i6n 1Ma3l8e0,dRaHs.26159: Repested-Dose Dermal Tosicy Dupo13882 Ex swayvo:JY | 5 camacsausr s { | stcGemioesBTMT L eBieSee mTOOa T i pr i SBa mee omel ul i || 52s=s=s aa ii 1 SE. fo=e] i}i --_ i i Spates ErinRet EE . reran i Peso CompanySaniized. Doesnot conTtSaCAiG8n1 --- 15B26e17S,a5y203ache2612: ReDosDpe Ttoy roma : a | ---- | |: i ST E ST E pE rr e e ans, E WhIboedm i | |I|||| BES SmEL UmpmarsTe cmhmIeiNe.. mRaTg oOrE ! {|| I SE Jro=oyr i;i | Erm Not:Baiosatisonybemiofo bon specif 4s hd ii Ll order 1 voidcomuminafion, heoe of deposit lbw i ! --~ | r EE r ---- | mISvIASASTERNLINY |i! 4 EDE FmEo E Ri E Ee E e: sThhg ienintscion ks i i 304.Soui 3om0onsrns om im1 TRts yS; eoee || f I) = roTe ote:Thsocom caneprovidfo pee,secotoevleoss. ||i J . en!t `ExypenResearch PageS10 63 ~ -- = Company Sarita. DossnotcoTnSCaAGnSI _ 51D26e15S, 5y261v5%, 0e452619: ReDpsDreaosdc Duran : esr --_ ' i r purr rs PTT | | 1. SSmimUEmSLITaoTET CalitraionStandards Thesesamdiedsa prepaved i contemosiky |i i| i P E mR tommemreateTs: E J EE ThetyR yrrdE peeta]s || . T E f E eo pE E er E r gE See aie | { BRIriEaoRinBte soemt ee i -0 || ii Sa SBErEaTn SEEaAdL T iE e i | nie | eR TS : bS r fR onfAaeL r ofL 10pp fcy CO by i| j | E a Smp y ar dT et e.i = C ER TcE ag ot rama reress || - . Progam falicaionstudardofG01pu.for ing. i Spot neizetes _ ee ---------- ere Company Saiized.Doesnot contaTiSnA G1 --~ 28H2D6a13y7S,ud2y6i13M5a,eenRdats26139:Repeated DoseDermal Toit Dupon13882 Enso NY i; | m Sa R s teE "R sea deci Se inmre ge ; i P Smu ae 6 fT r EsEpdNoIoEBo ii - !i| Tc E o oclintb on snt idY e ercs Boh SS einEdic, t | V a t fms ii}{ SmI W esn N m woo% S--oeu sa i3 | ! 802- 8 8 ~ :i + amo i TrxNSarorneenig--pEttF eEtd-- eE : nSoE , eomse by niet :|| i i Prosipeinin scoicle enc i mis ii = =.@sumstiosme = - i| + - NI o mpl prsesiaE gIs onddfo TeE maE pes.I BlwereE sI , rs E sis : Sons a [r-- hese Te ee e Company Sanitized. DossntcontTSaCAiGanl --~ 552D6127S, By2m6ean1Re2361385: Repost DoseDems ose Dupe By styvo !! soredrebatedssoyakebealowedfi" stemsmere, 4 | or | | 43.Suserea Pamanarion | i p SEmmeTme tot mler ee Exchbah ofimple exci iphcly30ocJi ict mcs aJi | J ---- so i | me et Frten viy mvey i |] Mf p r Sr y e tad p shetty ! : 2 ;: fArE C BddcRaonEgm hse ExmiRntm eEoceiE une gm.ndsandK 1T0L005 pl. i ; ~~ i| 44551.QuLuormtmsannmpmies tesu | SCI Tho komSpryLinedIroc nce i se * ecrsiorsi ! Sofowace: PESciexAnalyst 12 i . x BE-- kea i r [f aEcr e y e m a n i e SpAEss !|; BtTwo 4 10 mumbypercerhdrop guardcaida(Keystone,put # f Prats rein `ExypenResearch. Page 54.0f 63. ~~ TT ---- pr ----eee. CompanySaiized, Dossnot ontan TSCA 1 ~ 2ISD,S5y2615t8 0h45s2615: RepeDetTtsiocy Dares : se . : || E SREgeriiEA w ---- " !| i!|| SSryTORE7rosso8E me888TmE es ! | EPoss 8 3 8 = i | pmbe ay beLp cnt || | To| mo: =a wines AEE !{ 7 . E If pmetTo r LRia~me eirt mt"eenerae : S mie r a | |i fSE errEe EmSc ROSE e mr aIbi TiEicoT | [i| = iPpmrrESITEEENERTS ! J. . roves I EienResearch Page SS0(63. ~ BE CompanySntzad. oss not conTtSAiCn1 --~ A0 2Hb206y1Do37StuHyda2iMn 6Malae1enhdR3saHs.s25613,9: ReDopseDtel Toxicity oDwoenusisss62 sows i| tS a Ee etn see ttcemcd eiC,an egiea eirnss | :i|i ; E Se i EEa EsT n RtSnTPe ERm ATS fE LrENiSTe i ji Bon n a a The echelon couficient (1) for calfiwion cucves generied mat be. o 54 soe Tre 510mtncmS itseT recr. i i Ema | --_ i . mmm Sandardscoeaponing to alesfive cx ove ccocesrationlevels us be S2S 8 nEfTciI Ste s RS RcLtt A IepiSt+ } |i SSsee mnToERLEEELI ASIS Sm aR n ; {1 DE emmE e S eT eI tiEm : :i EEnR= nEe 5038 ma Se es ii i Stotmeas ngi 58 0S R'on Lom : Bott i mt esdnti om FC oSeaaNhaRomEendLedLpeegce y Ca} |i - I Eanes . Pe i Soi Ror restores ~ _-- Ee Company Sanitzed. Does not containTSCA CBI -_ 32o6y1uS3y7e,St5y:2i61M3e5e,eranwdas2e61350 , RepeatedDToe DFerTTricThy Duurreenasisee2 . --_] ; mt mb crnntttaie i {{: FJrryv------ve p; e peoA wd cod ii k T SuE sanT , | i Ey ---- 5RS n I ptsa cR E s A pL psE versy. | SmeunEnnemmaSEeRaAeLsL | --_ ; S r tmm Ey eEnSsrao mente femmttFm eselet s este erEiE { EFETiRrm m ie msr rBETTe ES 5.Thecomelaioncocficient(5)forcalibmioncaverganarated octbe. ||i : iE E e ireect te oe t ey { PSEEEEcin mtscov 0es 10 EE se ss me Gis citmion yamct bemet,optimiza aedcheapofastumestopening Po T! -- Epos rasan | Jr --_ em--------------En reesei Company Santized. Doss notcontain TSCA Gal ~~ bT ESyEmteme-- T -- Y vpreaisee - Eats4 |; | EE SEe --I --REECr yE eEr LsR eTE tr SoT rTo !i|; E S APpefrr mEm EiSrrar | + aFE romRnE e ---- " || | ~ ; R S EySs sR mmm R oenti--- | | mwpsei . 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Doesnotcontain TSCA CBI ~ 2H52.6D1a3y7S,toHd6y1in3M5oendRa2ts6139: RepeseDose Dermal Toss DuPonc1ss2 sores oY || Figure.SRteipnrsgettaotriQoe Rurwoimht-oSgrLso.f o8Cf oQtUoEMEaRse Seren | t rie . i | P . f | ir L| OBiE i 2 i ! |. ) Sete Epp Beh --_ --_-- } lo | | . $ - ! k [eT } stor CompanySanitized. Dossnot conTtSaCAiOsnt ~~ 2H8DLay S2y266i1n31M5a,la3endRHat7.s2.61,39 RepDoeseDaermatlToexicdity Dupont13852 : ---- |i Fic. RT eprasntatC iveChrooefa 1i0pobe Sgtudrdafo : | -E= 13. i 1| tt) a { | BET : || I} : Fem Ls ~~ Ee i -- Bl * : To - :: { | | i cfriemenal |1 i Bop A [ penRect ize --~ Pe Company Sanitized. Does not containTSCA C81 --_ E SEr -- non open ! orSy p y eerre i Fortifiedat 10ppbwitwih th ~SgE /mLoP fVC. ! | --- i Er 1 i| BEii . ! wT : : -- . ssn 8 ; | EEFi . | ! | it - :3 : Sarusdeen | ! rEBe] | . rows} Exypea Research Page 6301 63 _-- CompanySrc, Dons cominTSGAGSH -- 2F8L2-6D1a3y7S,t5ud2y61in35M,alaeodRaFt-s26139: Repeated Dose Dermal Toxichy DuPont13882 --~ APPENDIX G INDIVIDUAL ANIMAL CLINICAL PATHOLOGY DATA --_ -- Tie EE -- CompanySanitized. Does not contain TSCA CBI --~ F2-82:6D1a3y7S, H-t2i61nu3M8a,ldaenRdaytHs-26139: Repeated-Dose Dermal Toricity DuPont-13852 INDIVIDUAL ANIMAL CLINICAL PATHOLOGY DATA EXPLANATORY NOTES Individual Chinioal Chemistry Values: TG 1 Crisiveerides Individonl Drinatysis Valves: &tthhveearlesiudwmapsTleesniwpiautstfcciolcuoiltedenetdnots(ibm1e0pTl)cebifaoirnedt.est(iRngV (5) fhe"sEimpLle vaMs LavSailEableEfeor eSesciSnlg l(eNRe)n ~~ -- -a_____________ CompanySanitized. Does not contain TSCA CBI --_ Fa EEeLt,Gy2613, ta26155, Repent Dee Des ost Durani335 [A wa we IsxmE2E @EBom BEoEm Sh53m3 I:3 op F%f an we SL 3% E EooE EE E BE BE 3EboE - BEEZ % --_ emesor ea ensg-- e -- CompanySantzad.Dosno contTSaCAiCna ~ E 2607536a 10 52613 eeDrd Tic ois nts ees Stns vn tn ABmE B oalomE EsoE m mEosuoEE e R mE sior 2spQ a sOoOGned EPEEEER E 33 [ER E EE 2EEE 2EEE 2 E E GL4O OR31 ~ eee Company Sanitized. Donote contsain TSCA CBI --~ H2_82D6a1--3y7,SuHd-y26i1n3M5a,laenRdaHt-s26139:Repeated:DoseDermal Toicity le, Gre 3 - en HR m0 we us wawo we5i% 4E3 S3 BS Sk FH wo si eI WSS Individual Meisal Clinica) macs - ban Pathology Daca ri FwoRmooSehs wa Sk wwoe ewrefe woBo oooEase AiBY EI _ e Durony t13882 -_-- Tier CompanySanitzod. Does notcontTSaCAiCBnI --- 5261S37e1260, 4152615: RDa osDerm d Tx irvine ict ion aa -- EW BE 8 505. 0 sle om mo Bo oH 0 es isle pcan ~ --_-------------- CompanySunics. Doss conanT5CA1 --_ 2E62-6D1ay7,SuFd-y26i1n38M,ilaendRaHt-s26139: Repeted-Dose Demnal Toxicity DuPont-13852 eeeeeEERO, --_ APPENDIX H Individual Animal Final Body and Organ Weights --~ ET -- -- CompanySanitized. Does not contain TSCA CBI ~ gL. i IE aia iHH | |sBissisiiisse sR jog BRsiiiil ~ FE E(saRsaapiatan 5ar) R(Ey iEasEhiRazEe) &. {TEIg TnPEed; ' | 1 la izsessssses ssl lg. lsssszasl | | | FjfjIEEIEEEEEEoR ) fpmamsedi E8i B |P}oE ohls lsssnersens veEPIlap.dlepsssnss)i| | EEE GEE SEE gg,0ol 0 |B BiesBIsNgEmERsEmGeERnEeD mRnB)D mNeEeEaEmaEaEnEl 4 ed | | sii;isreenese3e2s) Biaieaeanaal 23 59 || || oGijg--j{saSmfs0s9ss2m8E3r8R3n8i) oy iESSREASR| Tip ammmssasl 4 4 - DUEL EEL CompanySaized Dossnot conTtSaCAiCont ~ o it id 31 Egl EiR spBEEEL sgssem ne ~ iy fps Ey pmsbi g SE i Blois, ammng LEE EEE FF EEE REE Et : 23 | 1 [ggise um Gipgisssnesssss agi i HIE REE I --_ =8 i Pd demlcmmmed Sem mmm EH C : Gompany Saitzed, Dossnot sonTtSaCAiCBn1 --~ 3 El lial gh i IE qogsns ~ Tis $ BL 0E iEsasessseans un sin .| 11 ET igemazieaie sai 2g Bgl | a iE 333s 358502o 8 adi gl | Hamma! ga 1 oPpEi EE , i | ii i : -- E 2H-82-6D1a5y7S, tF-y26i1n3M8a,laenRdaHt-s26139: Repeated-Dose DermalC Toxicity Dupont13852 --~ APPENDIX I Individual Animal Gross Observations -- Tm ---- Company Sanitized. Does not contain TSCA Cal -- 2H-2D6a1y37S,u1d2y6i1n3M8i,lae RdatHs26135: - RepDoseeDsermtalTeosicdty Dew Dupont13852 STUY: GE S(h+oAwienPgRoVaEnIDinzdaFilRvoirddoauccaaolsAfno)irmai)nciLviisdtuisn]g animals Date: 3-rzm-ot3 Dose Groth: 1 #-26136 Treatment: dex: Males Animal Rat Macroscopic Findings nly 01 AKTnieilrmlmaeilndalo{n3Ssbaaicyg.rnie+idc5eo8ff from necropsy Ho MaLiIcnVzTEoRRse,kcToEpKDiIcDNEAYbSn,ormTaHlIiRtGyIDobGLsAeNrDv,edSKIN, TRERED, SKI, 102 ATKnieilrmlmaeildnal3onSsebiacgyrnief:dic1o8e f from necropsy No ManLcimvreoRssh,cEopKDiIDcNEAYbSn,orTmHaYliRtOyIDGGbsLearbv,edSK:IN, TREATED, Ska, 103 AKTnieslralmaeildnal{o3nSasDciagryniet:dic5oe8ft fron necropey Mo MvaLIcmvraeonzs,ckoepKdiIGcNEAYbSm,orTmHaYiRtOyIDObGLsAeNrDv,edSKIN, TREATED, SKI, ~ 104 AKTieilrlmmeindal{o2nsasDaciyrgnief: dic38oeff from necropsy No MaLUIcNVxTEoRRsE,AcToEpKDiIcDNEAYbSn,ormTaHlRiGtIyDObGLsAeNrDv,edSK:IN, TREATED, skiv, -- - wm Company Sanitized. Doss not contain TSCA CBI ~ 28F.-2D6a1y37S,tH-d2i61n3M8,lesRdatHs-26139: RepeDoasetDeermdal Toxichty Dupont13882 STUDY: N. MEA.(S-hoAw5iPnRgOVaEnIDinzdaEilRviOddTauOtaCalDLAfno)irmanldiLviisdtuisn!g animals Date: 3-E-of2 Dose Group : I H-2136 Treatment: 3 Sex: vales Animal Ret Macroscopic Findings only ios AKTnieilrmlmaeildnalo5nSsaDicagrynief:dic36oeft from : necropsy No MTaLIcRVrEEoRAs,cToEKpDIiDcNEAYbSn,orTmHaYliRtOyIDObGLsAeNrDv,edSK:IN, TREATED, skin, 108 KTielrlmeindalon saDcaeyif: ic36e Anizal {3 signed off fram necropsy No MOaLwIcVEzERoREs,AcToKEpDiIcNEAYbSn,orTmHaYlRitOyIDObGLsAeNrDv,edSKIN, TREMTED, Kv, 07 KATnieilrnlmaeilndaliosnsasbciagrynief1dic3o6e t from necropsy No MaLOIcNVrTEoRRsE,AcToEpKDiIDcNEAYbSn,orTmHaYlRiOtIyDCbGLsAeNrDv,edSKIN, TRENTED, skrx, ~ 108 KATnieilrnlmaeilndaloinsssDaiacgyrnief1dic5e6off from necropsy No MaLOIcNVzTEoRRsE,AcToEpKDiIcNDAbYn,ormTaHlYiRtOyIDOGbLsAeNrDv,edSK:IN, TREATED, skin, --~ me `CompanySanitized. Dossnot contain TSCA CBI 2F-52-6D1a3y7S,tu1d2y6i1n3M8a,leanRdatHs-26139: Repeated DoseDermal Toxicity ~ DuPont-13882 DsotsoerGrQ oup ; E 1 #261S(3h+6oAwFiRTnRrgeoavatEnImDinendnaiStlvhsioddtuaaatelasAfnoSfirSemxai:lndMiLavilisedtsuisntg animals Date: Animal Ret Macroscopie Findings only 165 AKTnieilrmmlaielndalo5nSsabicagyrni:efdic3o6ef from necropsy Ho MaOLuEcIVzREoERsA,cToEpKDiI.DcNEAYbSn,orTmHaYliRtOyIDObGLsAeNrDv,edSK:IN, ;TREATED, skiv, 10 AKTneiirlnmleielndal'o3nSesDciagxyni:etdic2o6eft from necropsy Yo MaOLNEcTVrREoERsA,cToEKpDIi.DcNEAYbSn,orTsHaYliRtOyIDObGLsAeNrDv,edSK:IN, TREATED, skix, 3-rma-of3 --~ --_ -Y Company Sanitized. Doesnotcontain TSCA CBI 2H82-6D1a3y7S,uHdi2nM6lea1nRda3Ht-s28613,5: RepDoeseDaermtalTeoxicdity --- DDuiPonte138m82 STUDY: GEE S(h+oAwPiRnRgOVaEnIDinndaiRlvoirddouacatelaLAfnoofirmailnciLviisdtuisntg animals Date: 3-rzm-0f5 ADnoismealGrRoaufp i III H-M2a6c1r3o7scoTpriecatmFeinntd:ings ToYnly Sex: Males or KATinelirlmmeaidlnal5o3nSsaDicagyrnief:dic3oe8 f from necropsy Ho MUaLNIcTVzREoERsA,cToEpKDiIDcNEAYbSn,ormTaHlYiRtOyIDOGbLsAeNrDv,edSKIN, TREATED, ski, 302 Terminal sacrifice . AKniilmlaeld {oan sDiagyne:d7o6f from necropsy Ho MaOLcwIzrVEoRRsE,AcToEpKDiIDcIGAYbSn,ormTaHlYiRtOyIDObGLsAeNrDv,edSK:IN, TREATED, sKiv, 303 AKTnieilrmlmeei)dnaliosnSsDaiacgyrnie+idc2eo6ft from necropsy No MaTLcIRzVEEoARs,cToEpKDiIDcNDAYbSn,orTmHaYliRtOyIDGhGLsAsNrDv,edSKIN, TREATED, skin, ~ 04 TKielrlmeidnalon sbeacyri+ic5e6 Animal 35 signed off from necropsy No MaLONEcTVzAEoZRsA,cToEpKDiI.DcNEAYbSn,orTmHaYliRtOyIDOGbLseArDv,edSK:IN, TREATED, skin, --_ -Y `Company Sanitized. Donotecontsain TSCA Cal -- H2-82-6D1a3y7,StHud2y61in35M,alaendRaHt-s26139: RepDoseeDearmtalTericidty DuPont-13882 smooy S(h2oAwienRgROVaEnIiDnndaiPlRvOiTddOuaCatOlaL.Afn3o)irmailndiLviisdteisntg animals Date: 3-rE-0i5 Dose Group : III B-26137 Treatmants Ti Sex: Males Animal Ret Macroscopic Findings only 305 ATKneiirlmmlaielndal5o3nSasDciagryn:iefdic3o8eff from necropsy No MaLoEcuVzrEoRRsE,AcToEpKDiIDcWZAYbSn,orTmHaYliRtOyIDOGbLsAeNrDv,edSK:IN, TREATED, skrw, 306 ATKneiirlmmlaielndalo53nssDaiacgyrn:iefdic3o8eff from necropsy No MaLoIcwVzTEaRRsE,AcToEpKDiIDcNSAYbSn,orTmHaYliRtOyIDObGLsAeNrDv,edSK:IN, TREATED, skmv, 30 ATKneiirlmmlaielndaloinsssDaiacgyrni:efdic3o8eff fram necropsy Ho MawLcIrzVREoERsA,cToEpKDiIDcNCAYbSn,orTmHaYliRtOyIDObGLsAeNrDv,edSK:IN, TREATED, Skin, ~~ 308 TKielrlmeidnalon sDaacyrif: ic3e6 Aninal 53 signed off fxom necropsy aveDsILATATION, RIGHT, pEivis Yo MaLcIzVEoRs,copTiHcYRAObInDorGmLAaNlDi,tySKOIbNs,ervTeREdNT:ED, SKIN, UNTREATED --~ -YY CompanySanitized. DoesnotcontTSaCAiCBnI 2H8-:2D6e1y37S,tuHdyi2n 6Mal1aenRda3Ht-s28613,9:RepeatedDoseDermalToxicity --_ -- DuPont13882 el Showing anIinzdailvidduaatla AonrimailndiLviisdtuianlg animals Date: 3-7E-0f. SDoTsUeDYGr:oQuEp III R-2(6+13A7ZEROTVreEaDtmPeRnOtT:OCOLTi+)f Sex: Wales Animal Rat Vacrosconic Findings only 305 TKeirlmliendalon SaDcaryif1 ic36e Animal 5 signed of from necropsy No MaLOIcvVrTEoRRsE,AcToEpKDiIDcNEAYbSn,orTmHa,YliRtOyIDObGLsAeNrDv,edSKIN, TRENTED, SKIN, 0 ATKneiirlmmlaielndalo3nsseDicageynife:idc2eo8ff from necropsy No MOaLNIcVTrERoREs,AcToEpKDiIDcNEAYbSn,orTmHaYliRtOyIDObGLsAeNrDv,edSK:IN, TRENGED, SKIN, -- --~ Bon -- `CompanySanitized. Doesnotcontain TSCA CBI 2H8-:2D6a1y37S,tuHd-y2i6n13M8i,saenRdaHts.26139: RepeatedDoseDermal Toxicity --- DuPon13882 aw stooy ; WER S(hoAwiFnPgROVaEnIDinndaPilRviOdTduOaaCtlOaLAfno+)irnailndiLviisatuisn)g anisals Date: 3-rEs-0q5 Dose Group: V #26138 Treatment: V. Sex: Mates Animal Ret Maczoscopic Findings Only " soi KTielrlmeidnalonsDaacyrif: ic28e Aninal {3 signed ofc rom necsopsy Ho MaLoIcvVrTEoRRsE,AcToEpKDiIOcNEAYbSn,ormTaHlYiRtOyIDObGLsAeNrDv,edSK;IN, TRENTED, SKIN, soz KZoirlmliendalon sDaacryi:fic28e Animal is signed off from neciopsy Ho MoaLvIcVmrEaoREs,AccoKEpDiIcWZAYbSn,orTmHaYliRtOyIDGGbLsAeNrDv,edSK:IN, TREATED, Skiv, s03 KTiolmliende)onSadcaryi:fic28e Animal {2 signed off from necropsy No MaLe IcVrEoRst ,copKiIcNGAbSn,ormTaElYiRtOyIDoGbLsAeNrDv,edSK:IN, TREATED, SKIN, ~~ s04 KTeirlmliendalon sDaacyri:fic2e8 Animal is signed off from necropsy Ho MaoLcIurVREogRs,cToEpKDiIcDNCAYbSn,orTmHaYliRtOyIDObGLsAeNrDv,edSK:IN, TRENTED, skrw, --_ -_-- Company Sanitized. Donotecontsain TSCA CBI PS 2162-6D1ay37S,tHud2y6i1n3M8a,lneRdatHs-26139: RepeatedDoseDermalToriity - D Dupm ont13882 DS ose Go rup:, V H-861S(3h8owEinTgrehaatnIminezdnaPitlvrsiddouanatVlavo. Afo+nSrieaxi:)ncHiLavilisedtssientg annals vate: 3-rEs-of Ania] Ret Hacroscopic Findings only 525 AKTnieilrmlmaielnda5lo3nSbsaaicygrni1efdic3oe8ff from necropsy Mo Ma[LIcVkREoRsa,cotpKiIDcNZAYbSn,ormTaHlYiRtOyIDoGbLsAeNrDv,edSKIN, TREATED, Ski, 506 - ATKeinrlnmlieandalo3nSsaalcyarnief:idc7oe6ff fron necropsy No MaGLIcRVrTEoRRsE,AcToEpKDiIDcNGAYbSn,orTmHaYlRiOtIyDoGbLsAeNrDv,edSK:IN, TREATED, Ski, 07 ATKneiirlsmlaielndal3onSsabicagryni:esdic5o8eff from neczopsy roverCsis, sruarzaas, ron, <a. ~ Ho MaLcIVrEoRs,copTiHcYROAIbDnoGrLmAaNlDi,ty`SoKbINs,erTvReEdAT:ED, SKI, UNTREATED s08 AKTieslrmlmeiadnal3o%nSDsaaicgyrnief:dic58eett tron necropsy Wo MaLTIcRVrEEoRAs,cToEpKDiIDcNEAYbSn,ormTaHlYRiOtIyDOGbLsAeNrDv,edSK:IN, TREATED, SK, --_ ws CompanySanitized.Doesnot contTSaCAiCBnI 28H-2D61a3y7S,tu2dyi6n M1laen3RdaFt-8s261,39: RepDoseeDesrmtalToexicdity Dupont13852 Dsotsoeve Animal Rot 505 s10 S(=hoRweipnRgovaEnIDinndaEilRvoirddeuacntloarfAon+]rimailndLiivsitdionag animals Date: 3-rzB-04s PE6128 Treatment: V. Sex: Males Macroscopic Findings only AKTnieilrmlmaeildnalo{n3Sbsaaicygrnief+dic3o6ef from necropsy A No MOaLIrcVzREoERsA,cToEpKDlIDcNEAYbSn,orTeHaYliRtOyIDobGLsAeNrDv,edSK:IN, TREATED, skaw, ATKneiirlmalatelndalo5nSsDscaiygrniet+dic3o6eff from necropsy No MauLcIrVrREoERsA,cToEpKDiIDcNEAYbSn,orTmHaYlRiOtIyDObGLsAeNrDv,edSKIN, TREATED, SKnx, -Y `CompanySanitized. Doesnotcontain TSCA CBI --_ 25H2D6a15y7S,u2d6y1in3M,ilaeRatHs..26135: RepeatedDoseDecal Toxic - Duponc13852 emu stor qu . Shorsog snIinndatlviddsaat)s aonrimatlnalLviisotuinntg animate AerRoves shores sate: 3-res-b1y0 Dose GEE: Seiad Far VIL B36135 Teenceents VI} Sox: Hates Sacrasconic Findings ony Sa AKTneiirimmTaienlaaeln5SbFseiey3rniet1ai'c5oe8te team necropsy o MLGaIceaEsRer,opsRtIcOwEArbSn,ormTaHiAiGcYysOSbisaewrpv,edSk:in, Teeazeo, serv, ez ATTeiernmsdaane)n3sn2aec0yeniet1oic5o0ett trom necropsy sonSehATNTIon, are, seis. 03 Ho MaLEcVrEoRs,copTiRcRGAIeDmoGrmAaRlDi,tySKoIbNs,erTvReEdAT:ED, SKIN, OvTREATED Terminal sacrifice K[iETmTesa on' sey 1 30 ~ Ho MiaFcxrrosrcoapss Nmommaiity GAbserrved son niTeilrnmeianal5e3nstSaeiornrii1ai'c5ce8ee trom necropsy %o MiaLIcnVrEoaRs,ccopKtiicnNsom,orTmaeiintyoOGbisaewrpv,edSK:IN, meatao, ska, --_ - CompanySanitized. DoesnotconTtSaCAiCani 52552.6D1a3y7S,o2d6y1i3nM6a,te0Rdt5s.26139: RepDosoeDsermtaTeoidt ~~ Duponti38s DSoosue:GoNME VIN R-Lseh1o3Hr5inRgFraTenEsincncaaStelhnvtoisdto.aentiealenavfinoSiirsaTlnsaeisxvi:isotaeislntgesaminuts outer 3-mzaoh perio Nacrasonic Findings only 705 K[Teroemipdnaesl Sacrific15e -- B No MGaLcarrvaoessncsoKpyircheAnosn,orTmaitviottyoobGsiearnv,eds:k, meas, sea, 0s Eo Tielrlmeidnalse snacri1ic5e5 -- No MaLEsEzEosREcopKtIcRYAbsn,orSmAavliatcytoGbCisaewepv,edshaw, matsp, skcw, or AATeirnemianal3sSalcirnieisc'eote trom necropsy No MaLScEizVoErsRcsopKatIeSASom,orTmeavliAsSytDObGsiearv,edSH I, ented, kav, --~ 08 RAToeiirnemsiddnal8sSacnriiat'ic5aets trom necropsy 45 MGaLceErVroErsRciotpKsiEcRNASom,oraTsalviatcytoObestearv,edsw:av, mentep, ska, -- -_-- Company Sanitzed. Donotocontsain TSCA Cal -- 2F82D61a3y7S,uHdLy26i1n3M8,ienRdaHs-26139: RepestedDoseDermal Toxicity Dupont13882 TT Denim suo: -- SR howino g anIinmdahilvoitddusaatclasAfonrimailndiLviisbtiien]g eninels Sacer 3-res-o2f Dose Group: MI 26155" Treatments VIF sex: Animal raz Macroscopic Finaings only vaies 705 ATKneitriemlsie]nda'le53n'SsaSeciyrgniefdic5oe0ff from necropsy #0 MfaLcIraVoEstRcospKiIcNEAYbSn,omTaHlYiRtOyIDobGLsAeNrDv,edSKIN, TREATED, SKv, mo AKTinelrilmsei]ndala3nSSaDlcaiyrnief+aic3o8ese trom necopey Ho MGaLvcIrzERoEsRRcToEKpDiIcNGAbSn,orTmHaYliRtOyIDOhGLsAeNcDv,edSinn, TREATED, sav, --~ ++" Listing Complete +rs --~ -_-- Company Sanitized. Does not contain TSCA CBI