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AR2%G - 2296 a7 TRADE SECRET Study Title H-25435 Repeated-Dose Dermal Toxicity 28-Day Study in Male Rats AR2R6 - 3296 DuPon11574 TEST GUIDELINES: U.S. EPA Health Effects Test Guidelines OPPTS 870.3200 (1998) SOeEctCiDonG4u:idHeelailntehs EffofrecTtess,tiNnugmobfeCrhe4m1i0c(a1l9s81) AUTHOR: Carol Finlay, B.A. STUDY COMPLETED ON: September 3, 2003 - PERFORMING LABORATORY: HEaLskdelulPLoanbtodreatNoermyofuorrsHeaanldthCaonmdpEannvyironmental Sciences Elkton Road, P.0. Box 50 Newark, Delaware 19714-0050 LABORATORY PROJECT ID: DuPont-11574 WORK REQUEST Noor:[SY SERVICE CODE NUMBER: - -------- `Company Saniized. Doosnotcontain TSCA CBI Tage Tf 150 H2-82-5D4a3y5S:tuRdeypienatMeadl-eDoRsatesDermal Toricity DuPont11574 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) except for the item documented below. The item listed does not impact the validityofthe study. Test substance characterization and stability analyses were performed at Regional Analytical Services (RAS), Deepwater, New Jersey. Noneofthe aforementioned analyses were performed under Good Laboratory Practice Standards; however, the analyses were conducted in compliance with ISO9002 regulations. Allofthe analyses are considered valid and sufficient for the `purposesofthis study. Applicant / Sponsor: E.L. du Pont de Nemours and Company Wilmington, Delaware 19898 USA. --_ StudyDirector: LaCasrsolFilH,u5.4. SafToxicoogist 1dipe-1003 Applicant / Sponsor: `DuPont Representative, Date -- Company Sanitized. Docs not contain TSCACBI _--_--sm e e e e -e 1282:5D4a3y5:StuRdeypientieda:lDoRsaetsDermal Toxicity --_ `QUALITY ASSURANCE STATEMENT DuPont 11574 Haskell Sample Number(s): 25435 Dates of Inspections: PCroontdouccotl:: NOcotvoebmebre2r1,122,0200203 November 19, 2002 `November 27, 2002 March 5, 2003 Records, Reports: February 26, 2003 February 28, 2003 March 3, 2003 March 17-18, 2003 July 16,17,18, 21, 2003 ~ Dates Findings Reported to: Study Director: October 21, 2002 February 26, 2003 March 3, 2003 March 5, 2003 March 18, 2003 | July 31, 2003 Management: October 21,2002 } February 26, 2003 March 3, 2003 . March 5, 2003 March 20, 2003 August 25, 2003 --_ Repored by--MesaQurl`yaAisemGaurAudnioes y S-Sptinn2rz re eee e (Company Sanitized. Dees not contain TSCA CBI 25035 RpesDeeeDl Toi --_ Diorio CERTIFICATION `We, the undersigned, declare that this report provides an accurate evaluationofthe data obtained from this study. _w--o -- leE g e oy Zs%w3 Sa er m Gf A" beia LFotEs i 2-Serr-zoez --~ uedby isl Dituin hil hf Finkey,B1 2 dept. e3 "Date. | --_ | = Ci Company Saniized. Dosnotcontain TSCA oat -- ~ [~ | H2:82D5a43y5S:tuRdyeinpMealeaRtatesDedrm-alDToorisciety DuPont 11574 TABLE OF CONTENTS Page GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT crm QUALITY ASSURANCE STATEMENT wanna3 CERTIFICATION orsursmmssmssssmmssssssssssmsssssnsssssmomsmmsnsndd LIST OF TABLES coccovmsmsmmmmmmmsosssmsassssssmsmmmssmasmnimmsn] LIST OF FIGURES coovrmsrsmsnsmssmsmmsssssssmssssssssssssssssnesmn LIST OF APPENDICES wocusmssmsmsmmsmmsmmmsmsssssssssssssnssnaon STUDY INFORMATION worms STUDYPERSONNEL comers 10 INTRODUCTION. 12 STUDYDESIGN.cosmammsmsmsmssssssmsssssmssmmsmmmssasssssssomssneld MATERIALS AND METHODS woconnsmssmsmmsssmssssmsssssssssssssnsio1n2 Au TEStGUIAEHNES verses FE sone12 TY Ds AE YG raresmmermmmmmmeonmmmmrmeermmed3 23.. FEenevdiraonndmeWnatra.l.Co.nditions... rea-- eiom------r-- crrmmr--m--e--n=m_ds3 BE. P5I. CHSealPtEhTMIOo0nic tPRoOgrIr aim ngoccs ...sesm------;14 F. ASSIgIMCNt (0 GIOUPS and SAY SIA... G. Test Substance Preparation and AAMRISIAION.......rovvrvrevrens mses 14 14 L.. Food Consumption and FOO ERICIENCY ......urerunrmrnronmsevseosenr en1S J. K. TMootrtaalliFtlyuoarnidneCalnindicPaelrfOluBorSooCctIancVicAAtciOd NLeSvelr EVIeUatsionis..s..t ...s .....1..516 L. CI.linHiecmaaltoPlaotghy.ology EVIsUAmUOmNav--.c--.ce.ovevvvaemr--ne--s--osnsssnssne--msn--son 16 25.. UClriinniacyalsiCshemisty... gm sr ----nrg-- cmm--wnm--em--1td M. N. ADOC SHBHSHCAl PAthOIOY EVAIBHONS......nrreemrns menses ADBIYSES crores 18 19 (Company Sanltzed. Doss not containTsc cay T -- | | 12.82D5a43y5:StReupyeiantaedl-eDoRsaetDsermal Toxicity Dupont-11574 `TABLE OF CONTENTS (Continued) Page In-Life ToXIC0M0BY csrrummmmemsssuesmssmsmsesssssssmmsssmsssssssmsssmsssssssssssssssssssssssnndd A. Mean BodyWeights and Body Weight Gains .............ccowuesrussmsssssssssssssssessmmssersen 20 B. Food Consumption and FOOd Efficiency ............oouuurmmssssssssssssssssssssssssssmssemsesin2s0s C. Clinical Observations, Dermal Evaluations, and SUrvival.............ceeesessssmsssnns20. D. Blood FINOADE ABYSS ccosrcnsumesmmormsommmsmmssemsmsenssessssessssmssssessmmmmondl BE. InLifo CoRlUSIong conensmnummummmmmmsnsmmussmsrmermemssssswnmimmmsmndl Clinical Pathology EVAIUAHONS....c.vvruermeenvessssssssssssssssssssssssssisms2on] Au HOMBIOIOBY crsersesrnserrermermes sens essersmsessmssmessesessesssessesssesesssssessersesmrerod] B. Clnical CHEMISIY c.overvserereressenerersereseresesessssmssesssssssssssssmmmeen] E. Clinical Pathology CONCIUSIONS....cevveevvnvrvesesssmesrssessrsrmmmsenn 23 Anatomic Pathology EVAIUAtONS.cwmmmmmmmmesssssmssssmsssssssssssssssssssssssssssssssssssnmsnn2sds. BO 7S C.. GOSS ODSEIVALONS corns 24 D. MiCrOSCOPIC FINAIES....rervrvsorerssvsrsvsvsrsmensesssesssessssssssssssssmemmsosn 2 E. Anatomic Pathology CORCIUSIONS ...vvvvvvrvsmsrsessesrsrssssssssssssssssssessssssmsissnssn2n4s CONCLUSIONS cecvscnscnrsmememsmmssmensmssminmmessmsrsmsssisisisssssmmemmmd RECORDS AND SAMPLE STORAGE ..c.cconconssummssssssssssssssssssssssssssssmssssssssssmssssdanS SS ------ J "Company Sanitized. Does not contain TSCA CBU I-- 1252.5D4a3y5S:ucRyien MplseRtatesDderm:alDTooxiscitey Dupont11574 ~ LI OF TS ABLT ES Page 1. MEANDAILYAPPLIEDDOSE VOLUMESFOR MALERATS ccc 30 2. MEANBODY WEIGHTS OFMALERATS ccc 3 5. MEANBODYWEIGHTGAINS OFMALERATS vcr 34 4. MEANDAILYFOOD CONSUBMYMAPLETRAITSON ccc 35 5. MEAN DAILY FOODEFFICOIFMEALNERCAYTS in 36 6. SUMMARY OFCLINICAL OBSERVAINTMAILOERNATSS ccc 31 7. SUMMARYOFCLINICAL OBSERVATIONS - POSTDOSINGIN MALERATS... 38 5. PERCENTSUROVFIMALVERAATSL ccc EE 9. SUMMARY OFHEMAVTALUOESFLOROMALGE Y RATS.. at 10. SUMMARY OF CLINICALCHEMISTRY VALUES FORMALE RATS. rr} 11. SUMMARY OFURINALYSIS VALUES FORMALERATS cv dS 12. MEANFINAL BODYAND ORGANWEIGHTSFROMMALERATS ccd 13. INCIDENCESOF GROSS OBSERVAINTMAILOERNATSScrc AT 14. INCIDENCESANDLESION GRADES OF MICROSCOPIC OBSERVATIONSINMALE RATS. 4 i | || | |~ `CompanySanitzed.Dosnotcontain TSCAcat | [ -- --~ | | --~ ! --~ | | | H-25435: Repeated-DoseDermal Toxicity 28-DayStudyinMaleRats LIST OF FIGURES 1. MEANBODY WEIOGFMH ALETRASTS cvs DuPont 11574 Page enero 88 LIST OF APPENDICES Page A. INDDAIILYV APPI LIED DDOSUE AL VOLUMES... messes 3 B. INDIVBOIDYDWEUIGAHTLS coven serene C. INDIFVOODICODNSUUMAPTILON. 66 D. INDIVIDUALCLINICAL OBSERVATIONSAND MORTALITYRECORDS... 68 E. INDIVIDUALCLINICAL OBSERV-APOTST-IDOOSINNGS wcrc 78 F. INDIVIDUALEDEMAAND ERYTHEMA SCORES. ........ erm 8 G. INDBI LOOV DFLI UORIDNELU EVELSA .....L .... SR ---- H. INDIVIDUAL ANIMALCLINICAL PATHOLOGYDATA corr smn 104 I INDIVIDUALANIMALFINALBODY AND ORGANWEIGHTS... -- J. INDANI IMAV LPAI THOD LOGU YDATA A...L .... nmin05 ~| Company Sanitized. Doesnot contain TSCA CBI | ' M0 2H5.b2.5Du4a3y5s:SeuRMedpyeustMcaldR-eDoeRastess.Deal Tosicty 000 oDuwPonnes1157 STUDY INFORMATION sunsane ToiFe NNRED Senso WE25435 a Haskell Number: 25435 Composition Known Impurities! | Sponsor: E. L du Pont de Nemours and Company ~~ `Wilmington, Delaware 19898 USA. Study Initiated/Completed: October 25, 2002 / (see report cover page) | - - `Company Sanitized. Dos not contain TSCA CBI BDH2-8y2D5Sa43yu5;dStyuRdieypneinaMtMeladle-eDRoRsaeetssDermal Toxicity PN STUDY PERSONNEL OwDuePownti11s5m74 Study Director: Carol Finlay, B.A. Management: Scott E. Loveless, Ph.D. Primary Technician: Sherman J. Gude Clinical Pathologist: NancyE. Everds, D.V.M. Management: Steven R. Frame, D.V.M., Ph.D. Anatomic Pathologist: PeteCr. Mann, D.V.M. Management: Peer Review Anatomic Pathologist: Steven R. Frame, D.V.M., Ph.D. John F. Hansen, D.V.M., Ph.D. Statistical Analysis: John W. Green, Ph.D. Management: Janice L. Connell, M.S., B.A., C.LH. Toxicology Report Preparation: Brenda Tiffin Cecilia Rowe Kee, B.S. Management: Nancy S. Selzer, M.S. ~~ Laboratory Veterinarian: Thomas W. Mayer, D.V.M., A.C.LAM. Management: Janice L. Connell, M.S., B.A, C.LH. - Company Sanitized. Doss not contain TSCA CBI F-25435; Repeated-DoseDermal Toricity BRaySPOMARRS esee---- EET -- SUMMARY `The objectiveofthis study was to determine the potential toxicityof H-25435 following repeated dermal exposure. The test substance was applied to the shaved, intact skin ofmale Crl:CD*(SD)IGS BR rats fo6r hours/day for 28 consecutive days. Three groups of 10 male rats were treated dermally with 10, 100, and 1000 mg/kg/day H-25435. A control group of 10 male rats was similarly treated with deionized water. The rats were observed for mortality, clinical signs, dermal effects, and body weight effects during the study. Food consumption was determined weekly during the study. Blood samples for total fluorine were collected on test days ~4,3,9, and 21. Bloodand urine samples were collected for clinical pathologypriorto sacrifice onday 29. All rats underwent necropsy for gross and microscopic pathological evaluation. There were no effects on body weight, food consumption, food efficiency, or mortality at any dosage. No clinical signs attributabtloe systemic toxicity occurred. No dermal imitation was observed during the study. Some fluorine was present in the day 21 blood from rats dosed with the test substance, indicating exposure to a fluoride-containing compound. This finding was considered to be treatmentrelated but not adverse. ~~ OGrrogsasnowbesiegrhvtastiwoenrseannodtmdiicfrfeorsecnotpiincafidnodsiengrsesopcocnusresfpaosnhtiaonneoinuseliythienrriantcsoifdtenhciesosrtrsaeivneraintyd.age `and were not present in adose response fashion in either incidence or severity. There were no adverse changesinhematology parameters. Aspartate and alanine aminotransferase activities were increased along with increased sorbitol dehydrogenase activities in ratstreatedat 1000 mg/kg/day. These increases were considered to be potentially adverse. Urine fluoride was increased in rats treated at 1000 mg/kg/day, indicating exposure to and `metabolism ofa fluoride-containing compound. This urine fluoride increase was considered to be treatment-related but not adverse. Based on the presenceofmildly increased liver enzymes at 1000 mg/kg/day, the no-observed effect level (NOEL)' for the dermal exposureofH-25435 under the conditionsofthis study was. 100 mg/kg/day for male rats. {i --~ * TthheeteNstOsEuLbstfoarnctehiswesrteudnyotiddeetfeicniedd.asThthues,hfiogrhetshtisdossteudayt,wthheicNhOoExiLcoilsoegqiuciavlallyenitmptoortthaenNt OefEfeLctasatdterfiibnuetdabblye to the USS. EPA (1985) and 10 the no-observable-adverse-ffec level (NOAEL)a defined by the European Union (1994), Company Sanllized. Doss not contain TSCA CBI | I -- 12285D4a3y5:StuRdeypisntMeadl-eDoRsaetsDermal Tocty Dupont 11574 --_ INTRODUCTION The purpose ofthis study was to evaluate the toxicity of H-25435 in rats when administered hdaezrarmdaslasfsoorc2i8atdeadysw.ithThriespesattueddy dwearsmailnteexnpdoesdutroesprtoovtihdeeteisntsisguhtbsttoatnhcee poovsesribalelihmuitmeadnpehreiaoldthof time. AGrroaunpgse-offin2dmianglestruadtsyrweacseicvoenddduecrtmeadltoapipldiciantdioonssaogfe sHe-l2e5ct4i3o5n fatordtohseag2e8s-doafy1e0,r6m0a,l5s0t0u,dyo.r s1u0b0s0tamngc/ek-grefltoe6rd chloiunriscalfosri4gncsonorsebcoudtyivweediagyhst.loNsosedseorccmuarriemdi.tatBiaosnewdaosnotbhseerlvaecdk,oafntodxnicoitteyst othbese2r8v-eddayinsttuhdeyr.ange finding study, dosagesof 0, 10, 100, and 1000 mg/kg/day were selected for STUDY DESIGN Group Number/Group Dosage (mgks) mT 1100 100 v 10 100 ~ vi 10 1000 MATERIALS AND METHODS A Test Guidelines Except as noted below, the study design complics withthe following test guidieines: + OPrfoftieccetoifonPrAegveenntciyon(,EPPeAs)ti(c1i9d9e8s).anOdPTPoxTiSc 8S7u0b.s3t2a0nc0e2s1(/O2P8P-DTaSy)DUe.rSm.aElnvTioxriocnimtey.ntaHlealth Effects Test Guidelines. + DOrogsaeniDseartmiaonl fToorxiEcciotyn:om2i1c/2C8o--ODpaeyrSattuidoyn. aGnudidDeelvienleofpomrenTets(tiOnEgCoDf)Ch(e1m9i8c1)a.ls410 Repeated Obenclayumsaelmealraetssawreertehetrmeaotreed.seTnhsiisteixvcseepxtitoontdhiedtnooxitcaoflfoegcitcatlheefofbejcetcstiovfefslouorrvianlaitdeidtytoesftthe study i substances such as H.25435. -_-- Company Sanftized. Doss not contain TSCA CB1 ~ ~~ - [| --~ | 218.-25D4a3y5S:tuRdeypienatMeadl-eDoRsaetsDermal Toxicity B. Test Substance DuPont 11574 s`Tuhbesttaesntcesuabpspteaancree,d Ht-o2b5e43st5a,blweausndsueprptlhieedcobnyditthieosnpsoofntsohreasstaudny.amNbeorebvriodewnncelioqufidin.stTabhielitteys,t such as a change in color or physical state, was observed. `Aplulropfotsheseoftetshtissusbtsutdayn,cealladtmoixniicsetfefreecdtswwaesreasrseupomretdedtoasbeaafvuanicltaibolneoffotrhaebsaodrmpitniions.terFeodr dtohseage. C. Test Species SOenptOecmtobbeerr2,152,00220,0w2,er4e4rmeacelievCerdlf:rCoDm(CShDar)lIeGsSRBivRerraLtas,bowriatthorainesa,ssIincg.n,eRdablieritghhd,aNtoerotfh Carolina. `aTvhaeilCarblle:CfDro(mStDh)eIlGitSerBatRurrea,ttwheassuspeplleicetre,dabnedcparuesveieoxutsesntsuidvieesbaccokngdruocutnedd aitnfHoarsmkaetliloLnaibsoratory. d"iThsiesasset.rain is also considered suitable relative to hardiness and low incidenceof spontaneous D. Animal Husbandry I. Housing Rats were housed singly in stainless steel, wire-mesh cages suspended above cage boards. 2. Environmental Conditions AAnniimmaall rroooommss wweerree amratiinfitcaiianlleydialtluamtienmapteedra(tfulrueoroefsc1e9n-t2l5ighCt)aonndaanrealpaptirvoexhiummaitdei1t2y-ohfou3r0-70%. dluirghatt/idoanrktocyhcalvee. aEdxvceurrsseiloynasffoeucttseiddetohfetvhaleisdeitryaonfgtehsewestruedyo.finsufficient magnitude and/or 3. Feedand Water `Tap water was LabDiet 5002 provided ad libitum. PMI Nutrition meal was available ad libitum except International, whenthe rats LLC were Certified fasted. Rodent : 4. Mdentification oPurtisoridteoofaistssigcnamgee.nt Atfotgerrouapsss,igenamcehntrattowgarsoutpesm,peoaracrhirlaytiwdeanstiafsisedigbnyeda acaugneiqcuaerd6-adfifgiixtedHatsoktehlel aanniimmaall nnuummbbeerrawnedreatnaitntdoioveiddouanltchaegteailidoefnteiafcihcartaito.n nTuhmebienrf.orTmhateiloansto3n dtihgeitcsaogfetlhaebeHlsasiknecllluded the Haskell animal number and the individual identification number assigned to each rat, D a `Company SanE itized.lDoosLnotLconLtainLTSLCA CBY --_ | | =~ | | ~ 2DuF2-8y2D5Sa4u3y5d:SyuidRenypMeinaatMleaedl-ReDaoRsatetssDermal Toriciy 00 00 0 5. Health Monitoring Program DDwuPoonwtu11s57n4 As specified in the Haskell Laboratory animal health and environmental monitoring program, the following those that procedures are performed periodically to ensure that contaminant would be expected to impact the scientific integrity ofthe study: levels are below * Water samples are analyzed for total bacterial counts, and the presenceofcoliforms, lead, and other contaminants. + Feed samples are analyzed for total bacterial, spore, and fungal counts. * Samples from freshly washed cages and cage racks are analyzed to ensure adequate sanitation by the cagewashers. Certified animal feed is used, guaranteed by the manufacturer to meet specified nutritional rspeeqcuiifrieemdehnetsavayndmentoatlst,oaefxlcateoexdins,tactheldormianaxtiemd uhymdcroonccaernbtornast,ioannsdoofkrgeaynocpohnotsapmhiantaenst.s,iTnhec.luding presenceofthese contaminants below the maximum concentration stated by the manufacturer `would not be expected to impact the integrityofthe study. `The animal health and environmental monitoring program is administered by theattending laboratory animal veterinarian. Evaluation ofthese data did not indicate any conditions that affected the validity ofthe study. E. Pretest Period 3UptoimnesararinvdaleaxtaHmaisnkeedlldaLialbyofroartoarnyy,ctlhienircaatlslywearppeaqrueanrtasnitginnseodffdois6readsaeyso.r iTnhjeuryr.ats were weighed Onthebases ofaccepbtodaybweilghetgainsand clinical signs, the rats were released from `quarantine on test day -8 by the laboratory animal veterinarian's designee. F. Assignment to Groups and Study Start Forty rats were selected for study use on the bases ofadequate body weight gain, freedom from clinical signs ofdiseaseorinjury, anda body weight within & 20% ofthe mean. The selected rats were divided by computerized, stratified randomization into 4 groupsof 10 `were no statistically significant differences among group body weight means. rats, so that there Dose administration with H-25435 began on test day 0 when the rats wereapproximately 8 weeks of age. G. Test Substance Preparation and Administration On the day prior to the first treatment, thefur ofeach rat was closely shaved to expose the skin from the back and trunk. On each dayoftreatment,therats wore plastic collars during the e treeeemeTe--Com-- pae ny San-- im tized. D-- ocse riot-- conT tain -- TS0C8A.CCBFI ~~ ~~ | H2-82-5D4a3y5S:tuRdy ien MaplDeoResaetDsearmtalToexicdity Dupont 11574 exposure period to prevent ingestionofthe test substance and disruptionofthe wrappings. area to be treated was marked onthe backof cach rat with a water-insoluble marker. The The approximate total body surface area coveredforthe 0, 10, 100, and 1000 mg/kg/day groups was. 1.2%, 0.1%, 0.3%, and 1.5%, respectively. The volume ofneat test substance or vehicle was not sufficient to cover 10%ofthe total body surface area. The test substance was appliedevenlyand as thinlyas possible to the test site. The test substance was covered with a 2-ply porous gauze dressing followed by successive layersofstretch gauze (no more than 8 layers) and self-adhesive `bandage. Each dayofdosing, the control rats received the same volumeofdeionized water as the high-dose treatment group. The rats were treated at approximately the same time each day. Groups of 10 male rats were treated at dosagesof0, 10, 100, or 1000 mgoftest substance per kg `body weight. The ratsweretreated for 28 consecutive days. The amountofneat test substance needed to treat each rat was based on the most recently determined body weight measurement andthe test substance density of 1150 mg/mL. `The exposure period was approximately 6 hours. After the exposure period, the collars and `wrappings were removed and the test site was wiped with a wet paper towel and washed with `warm tap water. The test siteofeach rat was thengently patted dry and the rat was returned to its cage. Control animals received the same washing technique as the treated animals. `The animals were reshaved as needed during the studtoy facilitate the evaluation of dermal effects. The entire area that was originally shaved (including the untreated control skin) was reshaved. The animals were shaved only after an evaluation. H. Body Weights All rats were weighed at 3-4 day intervals during the study. L Food Consumption and Food Efficiency "The amount of food consumed by each rat was determined once per week throughout the study. Individual food consumption was determined by weighing the amountofdiet in cach feeder at the beginning and end ofthe week and subtracting the final weight and the amountofspillage from the feeder during the week from the initial weight. From these measurements, mean daily food consumption was determined. From the food consumption and body weight data, mean daily food efficiency was calculated. J Mortality and Clinical Observations Tbehheavriaotrs.were checked twice daily for mortality and for signs ofillness, injury, or abnormal | Comoany Sanitized. Does not contain TSCA CE - --_ ~~ | [ | [ | | ZDH2o-8y2-5SD4ao3yd5S:ytuiRdenypMeinaatMleaedl-ReDeoRsatetssDermal Toriciy 0000 DDuuoPomnnti11s57m4 s`Tuhbestraantcsew.erTehoebDsrearivzeedSfcoarlceliwnaicsalusseidgntsoofstcooxriecsiktiyn ainmidtadteironm.alAedfjfaeccetsntafatreerarsoemfovuantlroefatthede stkeistn were used for comparison. The rats were also observed for clinical signs at each weighing. K. Total Fluorine and Perfluorooctanoic Acid Level Evaluations Btelsotoddaywsa-s4,co3l,l9e,ctaenddi2nt1oaEpDprToAxitmuabteeslyfroonme hthoeurorabfittearlrseimnousvoafltohfethfeirsttes5t rsautbsstinanecaec.hTghroeubploonod awaWsicrekfbroigledrattoerdc.h Tcohmebtuosttaliofnlumoeritnheocdonftoelnltoowfetdhbeydaanyal2y1sibslwoiotdhsaamflpuloersidweaisondesteelercmtiinveed by using Jelaeccktsroodne.LabTohreatroermya,iDneienpgwsaatmeprl,eNsewwerJeernsocyt.analyzed. Fluorine blood analysis was performed at E`ADdTdiAt.ionPallabslmoaodwwaassprceoplalercetdedanfdrosmtotrheedvfernozaecnaavta-o8f0alCl atots-2a0tnC.ecrCoopnscyenitnrtoataiotnuboefcontaining perfluorooctanoic acid (PFOA) ina supplemental report. will be determined. The resultsofthe analysis will be presented L. Clinical Pathology Evaluation AThcelidnaiycablepfaotrheocloolglyecetviaolnuoaftsioanmpwlaesscfoonrduthcetecdlionincaalllpaatthso2l9ogdyaeyvsaalfutaetrioinn,ittihateioannoifmatlhse wseturdey. pulrianceewdaisncmoeltlaebcoteldisfmrcoamgeesa.chTahneismeala.niBmallosodwesraempflaesstefdoorvherenigmhta(tapapornoldxcilomiangtiecylayl 16 hours) chemistry and mcaerabsounredmieonxitdsewaenresetchoelsilae.cteBdlforoodmtwhaesocroblilteacltesdinfursoomftehaecvheannaicmaavlawahnidlewtahse palnaicmeadl iwnaassuenrduemr tfurboem, aplrloscuersvsievdintgo asneirmuaml,s.anBdofnreozmeanrarto8w0sCme.arBsowneermeasrtraoinwedsmweiatrhsWwreigrhetp'rsesptaarien,dbauttsaacnrailfyiscies `was not necessary to support experimental findings. 1. Hematology Blood samples were evaluated for quality by visual examination prior to analysis. Complete abnlaoloydzecrouonrtsd,etienrclmuidniendgfrreotimcumlioccryotessc,opwiecreevdaeltueartimoinnoefdtohneabBloaoydersmeAadrv.iaWr1i2g0hth-esmtaationledogbylood asnmdeaervsalfuraotmioanlol facneilmlaullsarwemroerpehxoalmoignye.dBmliocroodsscmoepaircsa,llsytfaoirnecdonwfiitrhmnateiwonmoefthayulteonmeabtleude,rewseulrtes prepared from examination. each animal undergoing a hematology evaluation but were not needed for "The following hematology parameters were determined: red blood cell count hemoglobin hematocrit --_--_-- red cell distribution width absolute reticulocyte count platelet count ies `Company Sanltized.SDoTss nort cmonntaTinSTtSCAACC81 BDF2-8u2-5DS4a3uy5:dStyuRideynpieMnatMaealdl-eeDoRRsaetessDerma_l To_ric_iy _ DDuuwPonmtn.1i1s57m4 --_ `mean corpuscular volume `mean corpuscular hemoglobin `white blood cell count differential white blood cell count `mean corpuscular hemoglobin concentration microscopic blood smear examination 2. Clinical Chemistry S71e7rucmlincilcianliccalhecmhiesmtirsytarnyaplayrzearm.etPerlsaswmearefldueotriedremcionnecdeontnraatRiooncsheweDrieagdneotsetrimcisn(eBdMuCs)/iHnaigtapchhili2 PH meter and a fluoride-selective electrode. `The following clinical chemistryparameters were determined: aspartate aminotransferase: alanine aminotransferase: sorbitol dehydrogenase alkaline phosphatase total bilirubin urea nitrogen creatinine cholesterol iglycerides glucose total protein albumin globulin calcium inorganic phosphorus sodium potassium chloride fluoride ~ 3. Urinalysis Urine volume and appearance (quality, color, and clarity) were measured and evaluated visually, Areustpoecmtaitveeldy.UriUnreinCehceomnissttitruyeanntaslwyzeerre. seUmrii-nqeuapnrtoitteaitniwvealsy mmeeaassuurreedd oonnaa RBoacyheer CDliiangintoeskticAstlasTM (BMC)/Hitachi 717 clinical Advanced Osmometer 3900. cUhreimniestfrluyoarniadleyczoern.cenUtrrianteioonssmowlearleitdyetwearsmdienteedrumsiinnegdaupshiinlg2anpH |i cmoentceerntarnadtiaonf)l.uorSieddei-mseelnetcstifvreoemleacltlruordien,easnpdetcoitmalenusriwneerfelueovraildueastweedrmeiccraolsccuolpaitceadl(lvy.olume x | The following urinalysis parameters were determined: quality color 5 clarity volume osmolality pH glucose ketone bilirubin . blood urobilinogen pflruootreiidne" microscopic urine sediment examination | --_ ** FFluorridie deeterdminmatiaonvwnoas aa nalyzedb fonomEDhTd vA pilahsmaO.TA ie | -- erTn -- e SCoEmpEany8S3an7i3ti8ze8d..DD0o2c9snneottccoonttaainTTSSCCAACCHBl ZDH2u-8y2DS5a4u3yb5S:ytiuRdneypMeianatlMeeldR-eDeaRtsaetssDermal Toxicity --_ M. Anatomic Pathology Evaluations 00000 DDuuopwoniti1s15m74 `Rwaatsspweerrfeorfmaestdeodnafttheer r3atps.mf.oollnotwhiengatfhteerfninoaolncbleifniocraeltphaetirhoslcohgeyduelvealdusaatciroinf.iceA.llAatfisnaslacsraicfriicfeidceby daneessitghnesuinadaenrdweexnsatagnrguoisnsaatniodn.micTrhoescoorpdiecroefvsaalcuraitfioinc.e wRaastsrwaenrdeomeuatmhoanngataliztberydeactamrenbtongrdoiuopxsi.de The following tissues were collected from the rats: gross observations* liver" kidneys" thyroid gland (after fixation)" skin (treated and untreated) - testh ---------------------- a Gmirsossisnogbasneartvoatmiiocnpsamrasd)ewaatsngeecnreorpasllyfyoortwhciocllhectheids.topathology was not approprise (eg. uid, ufled fur, and b Organs weighed All tissues were placed in an appropriate fixative. (`Tpheercreanttsohfafditnahle fbooldlyowwienigghotr)gawnesreweciaglhcuelda:tedl.iveFr,inkaildnbeoydsy, waenidghthtysrodiedt.erRmeilnaetdivjeusotrpgrainorwetioghts | ~-- `necropsywere used in the assessmentof organweight changes. | sTtiasisnueedswciotlhlehcetmedatforxoymlirnatasnidn tehoesihni,gahn-ddoesxeaamnidnecdonmtircorlogsrcoopuipcawlelrye. fMurotshtergprrooscselsesseidontsoasnliddeasn,y | additional target organs from rats in the low- and intermediate-dosage groupswereevaluated `amdidcirtoisvceo(pci.cgal.loys.teSoaerltehcrtietidsg,rpoossdoodbesmearvtaittiso,nschfroornwihcitcahladmeirmcartoistciso,piccaldciualugsn,osainsdwdoeuflordmniottibeseof the teeth, toe, til, or car pinna) were saved, but were not processed for microscopic evaluation. | --_ _-- TeCompany STanTitized.TDootsesnlootfccoonntatianlTTSsCcAacCBEI 1252-5D4a3y5:StuRdyepMieletRaetDsde.mDTooiscitey -- N. Statistical Analyses Dupon1574 Significance was judged at p < 0.05. Body Weight FBoooddy CWoenisguhmtpGtaiionn Food Efficiency Organ Weight Clinica Pathology iSncaiidelnce of Clinical Inci`dOebnsccervofaDtieonnsna Efects Prliminasy Test ret occkor end? ovens;; rg SahppWeiWikitesst fofr tLaeopvmeeionneigsnegecsiFoaortnd or soma TrelminryNietshtosdnooftS|teparelliAmianasry ers ignifcant significant | Toone apo Ry `Sequential application" of| [paiPrw{miilsse ciommpareisfoornoc ow One-way analysis of Kruskal-Wallis test?" |varianEce IfollSowed with | floellyowed with Dunn's | v[Onaet-eawnacyne?anaftlyosislalnsoywseodfwith | fK[rlouostkwaeld-WwailtlhiosDtuersnt"s Cochran-Armitage x testfortrend" a Pairwise comparison and associatedpreliminarytests wer oly conducted ithe tesfo lackofrend was ~~ sivIgntsihfuiscSdah.natp.iTroe-SWihkaptiesrtowWaislnkoestwagstsignibfuitcaLnte,vKernussksaltWwaalslsifgnsitfiwcaanst,oawroebudstbvyerDsiuonosfDestu.nne es 4 IWBfohtnhefeenriranoncniiidnedcniocvmeiweduacaislonOnobsvtesarisgvnaeitfidiocnanats,burtecaosridgendificabnetinlgacekosfftihtnocccuerrrteadi,nthveanluF , ci lelstEixoahncstteweesrrto"p' weirtfs ohram.ed openrhfoarlmhefed wreichorhdaetdbvalliu.iFnodreaxaample, ifilirabin was reported a <.1, 0.0 was usd for any clclatons | | | |~ | -- Company Sanitized. Does not contain TSCA CB --~ ~~ ( | | --_ | H2-82-5D4a3y5S:tuRdeypienatMeadl-eDoRsaetsDermal Toricity DuPont 11574 RESULTS AND DISCUSSION In-Life Toxicology A. Mean Body Weights and Body Weight Gains (Tables 2-3, Figure 1, Appendix B) No effects on body weights or body weight gains occurred in any groupofrats dosed with the test substance, H-25435. B. Food Consumption and Food Efficiency (Tables 4-5, Appendix C) No effects on food consumption or foodefficiencyoccurred in any groupofrats dosedwiththe test substance. C. Clinical Observations, Dermal Evaluations, and Survival (Tables 6-8, Appendices D-F) No clinical signs resulting in systemic toxicity occurred. Red ocular discharge was observed in all rats during the study. Red nasal dischargeand swollenface were observedinrats in all dose `groups. These clinical signs are considered to be due to the wrapping/collar application procedure. Superficial wounds and hair loss were presenint both treatedandcontrol animals and were not considered test substance-related. The observationofdark eye in one rat treated at 100 mg/kg wasshortin duration, was not observed in any other rats, and therefore is not considered to be test substance-related. No dermal irritation was observedduringthe study. No deaths occurred. D. Blood Fluorine Analysis (Appendix G) `There was some fluorine present in the day 21 blood from rats dosed with the est substance. `This indicated exposure to a fluoride-containing compound and is considered to be treatment related but not adverse. Two rats treated at 10 mg/kg/day had fluorine levels below the limit of quantification (LOQ). The remaining 3rats had levels ranging from 0.52 to 5.96 ppm. The rats treated at 100 mg/kg had levelsoffluorine ranging from 0.54 to 0.78 ppm. Two rats treated at Company Senltized. Does not contain TSCA CEI --- ~~ ~-- | | || | ~ 2285-4D3a5y:StRuedpyeiantMeadl-eDoRsaetDsermal Tosicity DuPont 11574 1000 mg/kg/day had fluorine levels below the LOQ. The remaining 3 rats had levels ranging from 1.22 t0 1.38 ppm. All valuesforthecontrol rats were below the LOQ. E. In-Life Conclusions Under the conditionsofthis study, the no-observed-effect level for inlife parameters was 1000 mg/kg/day for male rats based on the absenceofadverse effects. Clinical Pathology Evaluations A. Hematology (Table 9, Appendix H) There were no adverse changes in hematologic parameters in males. The following statistically significant changes in mean hematologic parameters were considered to be non-adverse or not related to exposure to the test substance: + Mean red cell parameters (red cell count, hemoglobin, and hematocrit) were similarly decreased in males dosed with 10, 100, or 1000 mg/kg/day (statistically significant for red cell count at 10mg/kg/day, andfor hemoglobin and hematocrit at 100 and 1000 mg/kg/day). ``wTehreerenwoacsornroeldaotsiev-ercehlaatnigoensshiinpottohtehrerecdhacnelglesp,ardaemseptietersth(ere1t0ic0u-lfooclydtersa,nignediocfdeos,seosr. There morphology) that would be expectedwithprocesses thatalterred cell mass. In addition, red cell mass parameters for the three dosed groups were similar to thatof the control groups on a hirgecheenrttdhearnmuaslusatlurdeyd.c"ellItmiasslsikienltyhtehactonthteroalppgarroeunpt,rdaetchreermtehnatnsaindirreedctceelflfemcatossftwheere due to compound. Therefore, these changes were considered to be unrelated to treatment. + Eosinophils were minimally increased in males dosed with 1000 mg/kg/day (147%ofcontrol group mean). Due to the consistencyof change, this increase was likely to be due to cthraenagtemse.nt.InThadedrietiwoenr,eeonsoinootphheirlasltceoruanttisoonsfailnlleiunkdoicviydtueacloruanttssd,osanedd nwoitchor1re0l0a0timvge/hkigs/todlaoygic were withinthe rangeofthe control group counts. Therefore, although this change was possibly related to treatment, it was considered to be non-adverse. : B. Clinical Chemistry (Table 10, Appendix H) Amsipladrltya(taelaannidnealaamniinnoetraamnisnfoetrraasnes)feirnacsreeaascetdiviintisesomweermealmeisnidmoasleldyw(iastphar1t0a0teoram1i0no0t0rmagn/skfger/adsaey). to Inthese groups, mean activities were statistically significant, and were 133-144%ofcontrol for aspartate aminotransferase, and 200-222%ofcontrol for alanine aminotransferase. In individual - Comnamy Satz. Doss not canta TSA 07 LH2-8D2-5D4a3y5SS:otubRdyyeiinnpMMaaelleaeRRtaateDssedrm-alDToox~ics~itey DDuuoPwoniti1s15m74 --_ aalfsfoecitnecdrreaatss,edgeinnearfaflelcyteadctriavtistiiensboofbthotghroeupnsz,ymaletshowuegrhemeleeavnataecdt.iviStoirebsitwoelredenhoytdsrtoagteisntaiscaellwyas ddiefhfyedrernotgefnraosmetihnedciocnattersolhempeaatno.celTlhuelapr irnjuery.soHfieisntcnorleocgaisceeadlltyr,atnhsearmeiwnaesreesannodalstoerrbaittioolns in the liver. Due to the magnitudeofthe change, this effect was considered to be potentially adverse. s`iTghneirfeiwcaenrtecnhoanogtehserinadmveearsnecclhinaincgaelschienmcilsitnricyaplacrhaemmeitsetrrsy wpearraemcetoenrssi.derTehdetfooblelonwoinn-gadstvaetrissteicoarlly notrelatedto exposure to the test substance: + Awlaksal1i3ne6%pohfocsopnhtatraoslegwraosupmimneiamn)a.llyThiinscrcehaasnegdeinwamsalpeosssdiobsleydrweliatthed1t0o00trmegat/mkegn/td.ayHo(wmeevaenr, ctlhienimcaaglnoirtaundaeotofmcihcapnagtehowlaosgyveprayrasmmeatlelr.s.InIandcdrietaisoend, atlhkearleiwneerpehonsophaalttearsaetiaocntsiivnictyordriedlnaottive o`Tchceurrefionrteh,easlathmoeurgahttshtihsacthhaandgeinwcarseapsoesdsitbrlaynsraelmaitneadsetoatnrdeastomrebintto,litdewhaysdrcoongseindaesreedacttiovibteies. non-adverse. Bi(l1i3r3u%boifncwoanstrsotlatgisrtoiucapllmyeaannd).miMneimaanllayndinicnrdeiavsiedduailn bmiallierusbidnosceondcweintthra1ti0o0n0smfgo/rktghi/sdagryoup a(mgeea-nm:at0c.h1e2dmcgo/ndtLro,lirnadnigveid(ucaolntvraolluemse:a<n0r.a1n0get:o0.01.069-m0g./2d9Lm)gw/edrLe; wrealnlgewoiftihnidnitvhiedhuiasltorical ~ tarneiamtaeldsg:ro0u.p0s7,-0t.h3is3 cmhga/ndgL)e.waBsausneldikoenlyintdoibviedrueallartaetddtaottarceaotmmpeanrt.edRteogatrhdelceosnst,rotlheand other magnitude ofchange was very small, and non-adverse. + CAhlotlheosutgehrotlhiwsacshmainngiemmaallyyhianvcerebaeseend irenlmaateldestodtorseeadtmweintth, t1h0e, m1a0g0,niotru1d0eo00fcmhg/akngg/edawya.s very small, and was not expected to result considered to be non-adverse. in adverse events. Thercfore, this change was + T(r1i4g7l%y,cer1i5d0e%s,waenrde m1i8n7i%moalflcyonitrnocl grreoiuapnmsmaeelaendss;dsotsaetidstwiictahlly10s,ig1n0i0f,icoarnt1o0n0l0ymagt/kg/day m1a0g0n0imtgu/dkego/fdacyh)a.ngIencwraesasveedrtyrisgmlaylcle,riadneds wwaesrenolitkeelxypetcotbeedttroeartemseulntt-irnelaadtveedr.seHeovweenvtse.r, the Therefore, this change was considered tobe non-adverse. c`Tohnesifdoelrleodwitnogbsetantoinst-iacdavlleyrssiegnbiefciacuasnte cithwanagseuinnremleaatendctloindiocsael:chemistry parameters was + Minimally decreased albumin inmalesdosed with 100 mg/kg/day i C--~ | -_-- | EN7 Company Saxiizece. hDocesonomtcionTtaisneTsaeccay ~ ~~ . | --~ 2H8::2D54a3y5S;tuRdeypienatMeadl-eDoRsatesDermal Tonicity Dupont 11574 C. Urinalyses (Table 11, Appendix H) c`Thhaenrgeewseirnemneoaandvureirnsaelycshiasnpgaersaimnetuerrisnawlyesries cpoanrsaimdeteerresd.toTbheenfoonl-laodwvienrgses:tatistically significant + Urine osmolality was mildly decreased (629%ofcontrol group means) in males dosed with s1i0g0n0ifmicga/nktg)/tdoawya.rdTshimsinwiamsalalsysohciigahteerd uwriitnheavnolauppmreospriinattheistegnroduepn.cyT(hneortestwaetirsetincaollaylterations in other renal parametors on this study. The presenceofdecreased osmolality with increased usirginniefvicoalnucmee.,Tihnertehfeoarbes,etnhciesocfhoatnhgeerwcahsancgoenssiidnerreendatlopbaeranmoent-eardsv,ehrasse.no toxicologic + Uinriunreinperportoetienicnocnocnecnetnrtartaiotniownawserdeecsreecaosneddairnymtaolienscrdeoasseeddwuirtihne1v0o0l0ummeg./kgI/ndaadyd.itiDoenc,reases decreases in urine protein have no toxicologic significance. Therefore, this change was considered to be non-adverse. D. Urine and Plasma Fluoride `There was no effectoftreatment on plasma fluoride concentration. Urine fluoride (total fluoride excreted ovemight) was increased in males dosed with a10f0lu0omrgid/ek-gc/odnatayin(iTnegxtcoTambploeunI)d..Increased urine fluoride indicates exposure to and metabolism of Text Table I: Mean urine fluoride for males [PUarFaLmUet(enrg)units)| 80 |"11074 |[101902 T|10303.09 | %ofcontrolmean| NA | 118%| 130%| 220% Statistical significance is indicated by bod alcizd type E. Clinical Pathology Conclusions. . `Ianndcoanlcalnuisnieona,midneortmraalnsdfoesriansgeoafctmivailteiesr,ataslwointghwi1t0h00inmcgr/ekagse/ddasoyrrbeistuolltdeedhiyndirnocgreenaasseed aacstpiavrittaitese, in some rats. This change was consideredtobe potentially adverse. Urine fluoride was increased ifnlumoarliedes-dcoonsteadinwiintghc1o0m0p0oumgn/dk,g/adnadyw;atshicsocnhsiadnegreeidntdoicbaetetdreeaxtpmoesntu-rreeltaotaenddbumtetnaobno-aldivsemrsoefa. `tThheenroef-oorbes,cruvnedde-reftfheecctonledvietliownasosf1t0h0ismgs/tkugdy/daanydffoorrmtahleeclriantis,cablapsaetdhoolnotghyepparreasmeentceerosfmmeialsdulryed, increased liver enzymes at 1000 mg/kg/day. Company Sanltized. Does not contain TSCA CBI EE -- H2D-8y2D5Sa43uy5dS:tyuRdiynieMn MaapllDeeoRResaeaDssearmatlToexicdity --~ Anatomic Pathology Evaluations DuDuopwointi1s15m74 A. Mortality There were no early deaths. B. Organ Weights (Table 12, Appendix I) Organ weights were not different in a dose response fashion in either incidence or severity. C. Gross Observations (Table 13, Appendix J) `Awlelregrnoostsporbesseernvtatinioansdonsoeterdesaproenksneofwasnhitoonocincueritshpeornitnacniedoeunscleyorinsreavtesroiftty.his strain and age and D. Microscopic Findings (Table 14, Appendix J) ~~ All age maincdrowsecroepnioctopbrseesrevnattiionnas dnoosteedrearsepoknnseowfnasthoiooncciunreistphoenrtiannceioduesnlcyeionrrsaetvseorfitthyi.s strain and E. Anatomic Pathology Conclusions Under the conditionsofthis 1000 mg/kg/day. study, the no-observed-effect level for pathology was | | r---------------- Compan-- y Sanft-- ized. D-- oes neot-- ceont?ai-- nTTSOCAA CBI Tie e228D5-4Dy3aSy5u:SudRdeypyenianMtMeadl:oeDroRssaetssDermal Toc 000 0 --_ oDwupeown1n1s57w4 CONCLUSIONS fNoooddceoantshusmopctciuorrne,dodourdinegfftihceiesntcuyd,y,cliNniocaaldsverisegotrensdt essmuba,sltainrcietraetliaotnewderefefescetesnoinn bmoadlyerwaeisghtth,at rgreocsesivoebdse2r8vaatpipolnisc,atainodnsmoifcrHo-s2c5o4p3ic5 faipnpdliinegdsdwaeirlyetcootnhseidsehraevdetdosokcinc.urOsrpgoanntawneeioguhstlydiifnferraesnces, and/or were hematology onroturpirneasleynstisipnaardaomseteerrse.sponse fashion. There were no adverse changes in aDcetrivmiatliesadamlionnigstwriatthioinncorfeHa-se2d54so3r5birteosludlteehdydirnoignecnraesaseeadctaisvpiatriteastaeta1n0d0a0lamngi/nkeg/admaiyn.otransferase iTnhcerenaos-eodbsleirvevrede-nezfyfmecetslaetve1l0(00NOmEgL/kYg"/wdaays.100 mg/kg/day based on the presenceofmildly RECORDS AND SAMPLE STORAGE Athlel sdpaotnasaonr.d rLeacboorrdastofroyr-asnpaelcyitfiiccalorchsairtaec-stpeeicziafticioanswcdoantdau,cstuecdhbaystpheerssopnonneslorfiwlielslabnedreeqtuaiipnmeednbty. pe recordswillbereaibnyethdfacility where thework wasdone. ALabsoarmaptloeroy,fNtheewatreskt,sDueblsatwaanrcee.wiSlpebceicmoelnlsecitfedafppolriacracbhlie)v,e rpaurwpdoasteas, aannd rtehteafiinneadlartepHoarstkewillll be } rWeitlaliinnegdtaotnH,asDkeellalwaLraeb.oratory, Newark, Delaware or at Iron Mountain Records Management, REFERENCES i 1. SDtuuPdoynitnHRaastkse.llUnLpaubobrlaitsohreyd(2p0o02r),{H-2N4678T: S} ubchronic Toxicity 90-Day Oral Gavage. || 2.- DWrialpeeyr,,NNe-wR.Yaonrdk.Smith, H. (1981). Applied Regression Analysis, 2* edition, pp 266-273. |[ 3. aSneilmwayln,saMfRet.y s(t1u9d9i5es).. JTohuernuasleooffttrheenAdmteersitsctaon dCeotlelremgieonefaTnoox-iocbosleorgvya1b4l(e2-)e,ff1e5c8-l1e6v8e.l in || ~ +ThthheeetrNeisOtlEesuLdbfsStonaentcsiesEwnseviryronnoimteddneettfaeilcntePedr.oatscTththuieso,nbifAgogreestntcidysoadsa,nwdthh1iectNhhOtEonoLooiecisnocelqdgu-ivaaadllveietmrptoshrete-aneNtfOfoeEtcLvts2ele(iWne OeAoEyaL. | defined by the European Union 00 rer----------Co-- mpany-- eSanielize-- ed. Dioe-- s not co-- ntAainTT-- SSCAA CEY Ee ] ZH2-8o2-5Du4a3y5SS:utudRdyyeiinnpMMaeelleaeRRtaeteDssedrm-alDTooxisciety DDwuePomnti1i15s7n4 ~ 4. Jonckheere, A.R. (1954).A Biometrika 41, 133-145, distribution-free K-sample test against ordered alternatives 5. SLteavteisntei,csH(.3.(1O9l6k0i)n., eRdo)b,upspt t27e8t-f2o9r2.equSatlaintfyoofrvdaUrniiavnecressi.tyCPornestsr,ibPuatlioonAlstot.o Probability and 6. sSahmapplierso),.$.B5i.oamnetdrWiiklak,5,2,M5B9.1-(611916.5). An analysisofvariance test for normality (complete 7. Snedecor, 349-352. TGh.eW.IoawnadSCtoactherUanni,veWr.sGit.y(P1r9e6s7s),.ASmteast.isticalMethods, 6TM edition, pp 246-248 and 8. Dunnett, 482-491. C.W. (1964). New tables for multiple comparisons with a control. Biometrics 20, 9. Dunnett, C.W. (1980). Pairwise Statist. Assoc. 75, 796-800. multiple comparisons in the unequal variance case. J. Amer. 10. Tunaemqhuaanlev,arAi.aCn.ces(.197J9.)A.meAr.coSmtpatairsti.sAosnosofc.pr7o4c,e4d7u1r-e4s80f,or multiple comparisonofmeans with --~ 11. JK.rAumskearl.,SWta.tHis.t.aAnsdsoWcal.li4s7,, W58.3A-.62(1.1952). Useofranks in one-criterion analysisofvariance. 12. Dunn, O.J. (1964). Multiple contrasts using rank sums. Technometrics 6, 241-252, 13. Fisher, R.A. New York. (1985). Statistical MethodsforResearch Workers, 13* edition. Haffner, 14. DuPont Haskell Laboratory (2003). H-25509: Repeated Dose Dgmal 28-Day Study in Male Rats. Unpublished oor Toxicity 15. fHoarzAanradlyEsviasluaantdioEnvaDliuvaistiioonn,oSftSaunbdcahrrdoEnviacluaantdioCnhrPornoiccedEuxrpeo,sTuorxeicSittuydiPeostePnatyinatl:er,GuOi.dEa,ncofe a`lW,asUhniintgetodnS,tDa.tCes.,En2v0i4r0o6n.meEnPtAa-l54Pr0o/t9e-c8t5i-o0n2A0g.en(cJyu,neOf1f9i8c5e)o.f Pesticide Programs, 16. Risk EN), ACshsapetsesrmeI,ntSoecftiNoontsif2i.e2d4 Naendw 2S.u25b.sta1n9c9e4s,. Technical Guidance Document.(X1/283/94- ~~ -Y -------------- Company Sanitized. Dos not contain TSCA CBI YQ 2F-52-5D4a3y5S:tuRdeypeinatMeadl-eDoRsaetsDermal Toxicity -- DuPont-11574 TABLES --_ --~ Company Sanitized. Does not contain TSCA CBI Ea 12.82-5D4a3y5:StRuedpyeiantMeadl-eDoRsaetDsermal Toxicity DuPont11574 -- TABLES EXPLANATORY NOTES ABBREVIATIONS: `Summary of Hematology Values RBC - red blcoellocoudnt HGB - hemoglobin HCT - hematocrit MCV - meancorpuscular volume MCH - mean corpuscular hemoglobin MCHC - mean corpuscular hemoglobin concentration RDW -redcelldistribution width ARET - absolutereticulocytecount PLT -platelet count WBC - whiteblcoellocoudnt ANEU - absolute neutrophil (all forms) ALYM - absolute lymphocyte AMON - absolutemonocyte --_ AEOS - absolute eosinophil ABAS - absolute basophil ALUC - abslarogeulnstuaintedceell SummaryofClinical Chemistry Values AST - aspartateaminotransferase ALT - alanineaminotransferase SDH -sorbitoldehydrogenase ALKP - alkalinephosphatase BILI -totalbilirubin BUN -ureanitrogen CREA - creatinine CHOL - cholesterol . TRIG - triglycerides . | GLUC - glucose : TP - totalprotein | ALB - albumin GLOB - globulin | CALC - calcium PHS - inorganic phosphorous NA - sodium K - potassium ~~ CL - chloride PFLU - plasma fluoride `Company Sanitized. Does not contain TSCA CBY - 2H-82-5D4a3y5:StuRdeypeinatMeadl-eDoRsaetsDermal Toxicity --~ TABLES DuPont-11574 EXPLANATORY NOTES (Continued) ABBREVIATIONS: (Continued) `Summary of Urinalysis Values VOL - volume UOSM pH - utrhienleogoasrmoiltahlmoiftythereciprocalofthe hydrogen ion concentration URO - urobilinogen UFLU - urine fluoride UMTP - urine protein NOTES: `Summary of Hematology Values SummaryofClinical Chemistry Values ~ SWhuemnmaarnyionfdUirviidnuaallyosbisserVvaaltiuoenswas recorded as being less than a certain value, calculations were performed onhalfthe recorded value. For example,ifbilirubin was reported as <0.1, 0.05 was used for any calculations performed with that bilirubin data. Company Sanltized. Does not contaln TSCA CBI - | 2 2 | i- 5i i43 . ve ss 3 3 :s F a3 oF3 od a3 8 ed s eo a4 : ga 3 B 8o% 33% 3gs% g8n7 gnR gBdR g8d gf ge gd 3% %i . i 2Zs:3v53uf:435 3oS :55 oSgnzS miF :aS 3wf za3 STR gh gd gd gd dd dT AT RT RT ET Tf 3 8 3z & ss 335 3 3 3 35 35 3 3 gZ Hg 2020.830 0320 u3F 00%3of3e3f 3oF3Sof5Eo8SF 5San 53 4 2a : 2 28 Aa 8= 3=2~ 8= 8= =83= 883 3B 833 3= E2 owe 3%% 3%% 35%% 83%2 32 527a uBaR oB s 8oRsR RoRs EsRe g3 : it . 8f4e% 05% 55 035 038 2$f3 5# og8 3& i% | = &| IL~ d3 | i ieii 24"a z=& B: 52: 2 3 gf BL fg FiS = 2 E2E : 43 af a3 of 2% 4% 7% 25 =a =a a5 ang % 87 8% BR R7 BY BR RR IR RR RR AN og s: =3 32 5 8 8 z5 g53 &5 8 8 85 8 3 4 _g <% 9% tn ma an 3 9% ov ef ex ex 8 fe Ed BA Ze 84 Ze ad ad gd ged go El sz af af 3 af 3: of of of3347 AF8238 :A 8of z fEpprEriiiiil 5s 8 8 8 8 8 3 ne 4 go9m Sgm8 Sn% Sm8 o3m S3%7 853% Sg%d Sgu3 3&44 2 3 BMir : osF:3: i:33f :3f 3i : 3g3 PA = gB 3 2 3d 8 d8 86 58 gR ER { | 33 g 3% 28 38 .58 3 3 z Splat 3 ~8 memo omm 2g g 538 8 88 Ef5 oEeizaiaiazaizm . gE: =3 88 28 3 3 3% 83 55 ae 899% g98% gAT 44%% 3a38gaT 8e%n | a 3 5 5z i2 2 if 52g 05 3&8 5 3 i i 8: 2 3 2 3 |3 73 i ~ : E` 9 84 A% gn pn gd dA aR Lk T 33 sgl 3 33 283 aga 3 7 B7 27 8 BU BY 8% ER g8 2g 4 5s 8 3 FICE CECECE-LE CN ELL a zgz2 hh Bs wos EE 5 8 e2i % 8 m 8 8 a 8 8i 8 2 Z 7 ZN 98 G8 28 3o geogoo@ = se if E ii 3 H8E 4 .: i 3 Lt ii 35 is i$3: i8g s Fpz E5 F2E 025 0%5 28 33%BE |%[5% of [I 23 ii z& a& ~ li 5 I z - i32 23 8 2 35 3 8 8 8 3 3 Brora NnNE 3 5 333833 3 2s-%e:grorg: ioarazi aIaa | :4 : 3:33:33 o3| EE : 8 1 n% an an na af os aq we en - 2 na ne ae ge a an ad fd ea 2a Ll2 ew on xe men on a i 3 :Fi E Pe PfEf i+B 2 = E : s 3% "7 8 gd 4% 49 gd gf ve oF as sd z ;8 2& iigi 2% 3k 5 . 6 fspgf 8fF5 fo:8 f:i:8 :8 f|d e1;d ii ~ &8: E: i: : f ; 3 :: < 3 zzZS g5s 33 5883 ormEEE Rs33 ii 4ig 4 3 ss 2 8 & z 3LBa mg a8g g g 2 g 8i32 og2i sR oz z 4 : ; i: 8g 3333 3| 23 ddan n.d =g 5EM8 a 5g . zg 2 LE3 3 F +2 a i Bi ozEgi Of |1; 5 is Ey 3 it I LI ~ 3 & | | Te258383 82 8 SS So Ss es ss 3 ggg oz] i5 3gp o-3 ii ifiRE OE E He i EEE2 sL 2 BE RE Ss os oc ce se : gE ..ERiGiE 32 | 3 2% z 3% 1] E- T. 5 3 Cols 5 |Hi ai gfgif02:5 f % d: 3 ig 2 2 8 3 |% La3H is LI B 5E i 3 33 :i . 3 . i :: ; ]2 552 us FR 2i :Zs z 2 2: 58 28 gas id E -"8 a EAE li 4i ii2 5 x z] z2 E SEEE2 Te8 Ia 3i:; .5 NEE l 3 53 8ax a9 ig 3 5 g2 g8 ELEd f 3Z nes - :3 prtis Loin : ie : " 333 3 [8% -& i CF Fi 538 321 ii gfof ogif pcBf:sf2 4 3 $080 5 gi EE, iiz HgEdE ox Fxidou Figif ~ : 3 | | 52 i 2 i jd3: #9) 2232 uss 8 gi2 So... Z 2 g; ~2 8 8 xem o z Fz - ge 5iE g eae :gE = ge zf= F z Fz E we mm ng i i 2 _= _2 _05% i23 me am oan 5 3zzz zz ~ - - oe "8 it A & 283 g Ez 3 5i 2 h ona In z 5 Ts 5 1 : 33 1% : s #8.8 ofi& ifot gi82 i}85 i it 8 5 55 56 3B258i 3i, 3058 iis i331 3i 3H3 8B353E37E 5&o32 i4$,5 i2 33i +3E2 8 ~~ =5 =g 8 |LfH ss8gs% -oe } LgIo. : 8 3 asmli lgdkd 8 z2 "8 HiE: i if 8 | 522 iPIBHsiox 23 2 jig bE g Sh I~ 2 82g aHEs: P~ *PLEgEI8 s 4. 2E iY; ' za8E2 3 f5i5di || g2 zg zi * t[[fBdsgiCE3 5 nog Ee 233 Z iv :g 38i0ty8 : 2 lsd 3 2233 g8t2 4k iit: 212-5D4a3y5S:tuRdeypieantMeda:lDeoRsaetsDermal Toxicity DuPont-11574 TABLES PERCENT SURVIVAL OF MALE RATS Group: 1 m v vit Dosage (me/ke) 0 10 100 1000 Dayson0Test 100 100 100 7 100 100 100 110000 2114 110000 110000 110000 110000 2% 10 jo jo 100 Numberatstudy start Aliveontestday 28 10 10 10 10 10 10 10 10 Percent Survival = (Numberofrats alive/Numberofrats at risk)*100 Number ofras at risk = Number at study start b~ There were no statistically significant decreases in survival. | COMOAY Sali Me mt neta Tron com 28Day Study in Male Rats DuPont-11574 TABLE SUMMARY OF HEMATOLOGY VALUES FOR MALE RATS Group 1 0mghkg GroupI 10 mg Group V 100mekg Group VII 1000 mle RBCDA(xY1209/uL) 832 795% 7.95" 801 034(10) 036010) 036(10) 027010) HGB (g/dL) DAY 29 163 159 156+ 156% 056010) 06010) 0.6(10) 03010) HCT (%) DAY 29 482 466 46.0" 4s 18010) 1100) 18(10) 09010) Mev (@) DAY 29 580 587 578 571 18010) 18010) 1.4010) 15010) MCH (pg) DAY 29 196 200 19.6 194 05010) 06010) 0.6(10) 05010) MCHC (gL) DAY 29 38 340 340 340 03010) 06010) 0.6(10) 04010) RDW (%) DAY29 10 I8) 109 11 05010) 0.4(10) 03010) 0.5(10) ARET (x10%4L) DAY 20 1774 1905 1726 1851 49900) 422(10) 545(10) 35.5(10) PLT (x10%4L) DAY 29 1186 1277 1326 1265 . 1150) 1256), 157010) 175(8) } WBDCA(Yx2109%4L) 1205 1217 1285 14.66 32700) 3.04(10) 215(10) 242010) ANEU (1041) DAY 20 1.70 1.59 137 200 091(10) 0.57(10) 021(10) 07200) ALYDMAY(x2190uL) 961 9.85 1072 1169 232010) 27700) 2.14010) 182010) | Company Sanitizod. Doss not contain TSCA CBI Ee 282-5D4a3y5:StuRdeypienaMteadl-eDRoastesDermal Toxicity DuPont-11574 TABLE 9 (Continued) SUMMARY OF HEMATOLOGY VALUES FOR MALE RATS Group 1 0mgkg Group II 10 mg/kg Group V 100mgkg Group VII 1000 mek AMON (x10uL) DAY 29 AEOS (x10/uL) DAY 29 ABAS (xI0/uL) DAY 29 ALUC (x10%4L) DAY 29 031 0.12(10) 017 0.07010) 00.1042(10) 014 0.06(10) 027 0.06(10) 021 0.09(10) 011 0.03(10) 014 0.08(10) 031 0.07(10) 019 0.06(10) 0.09 0.04(10) 017 0.06(10) 041 0.13(10) 025@ 0.05(10) 04 0.06(10) 017 0.08(10) Dua amngedas: MSteaanndard deviation (Number ofvalues included in calculation) fGerwoeurpdsewciitmhaildelntaiccsatlhvaanluetshemvaayluveasruyisnedsfaoissttactaisltisciaglnidfeitcearnmcien,atbieocna.use tabulated statistics are rounded 0 @+ StaStiasttiistciaclalllyysisgignniiffiiccaannttddiiffffeerreenncceeffiroommccoonnirroolaattp <p< 0.005bbyy.DDuu0nestt5Teatrhane-Dunnettst. | Company Sanitized. Doss not containTSCA CBI = 21285D4a3y5:SRtepienuaMtidld-eDRoaystesDermal Tricity r~ Dupont-11574 TABLE 10 SUMMARY OF CLINICAL CHEMISTRY VALUES FOR MALE RATS Group I 0 mg/kg Group III 10 mg/kg Group V 100mgkg Group VII 1000 mgkg AST (UL) DAY 29 ALT (UL) DAY 29 SDH (UL) DAY 29 ALKP (UL) DAY 29 BILI (mg/dL) DAY29 BUN (mg/dL) DAY 29 CREA (mg/dL) DAY 29 CHOL (mg/dL) DAY 29 TRIG (mg/dL) DAY 29 | GLUC (mg/dL) DAY 29 TP (gL) DAY 29 ALB (g/dL) DAY 29 109 14(10) 50 8010) 28 29010) 201 37010) 009 0.03(10) 15 2310) 038 0.04(10) a 6(10) 30 10010) 91 8(10) 67 02010) 43 02010) mn 8010) 60 15010) 135 38(10) 24 37010) 012 0.02(10) 15 2310) 039 0.03(10) si 5(10) a 15(10) 97 13(10) 67 03010) 42 0.1010) 145@ 41010) 100@ 37(10) 206 10.510) 2s 46(10) 0.12 001010) 15 2010) 042 0.05(10) si10) as . 1500) 97 910) 65 02(10) an 02010) 157@ 79(10) me 66(10) 139 5000) 2740 52010) 0.2@ 0.04(10) 15 200) 041 0.0410) 57 610) 56@ 19(10) 101 1010) 67 02(10) a1 0.1310) | Company Senitized. Does nc contain TSCA CRY ws L H2:82.5D4a3y5S:tRuedpyeinteMda-lDeoRsaetsDermal Toxicity DuPont-11574 TABLE 10 (Continued) SUMMARY OF CLINICAL CHEMISTRY VALUES FOR MALE RATS Group I 0mgkg Group III 10 mg/kg Group V 100mgke Group VII 1000 mgke GLOB (g/dL) DAY 29 CALC (mg/dL) DAY 29 IPHS (mg/dL) DAY 29 NA (mmol/L) DAY 29 K (mmol/L) DAY 29 CL (DmAmYol2/9L) PFLU (ug/ml) DAY 29 24 0200) 108 0.410) 8.1 0.5010) 150.0 1.5010) 619 022010) 1024 1.6010) or 0.0(10) 25 03010) 108 04(10) 80 0.5(10) 149.8 1.6010) 605 0.40(10) 1025 1.9010) ol 0.0010) 24 0.1010) 105 03010) 79 05010) 149.7 12010) 622 039(10) 1039 1.5010) 01 00010) 25 0.1010) 10s 02010) 80 0410) 149.0 14010) 599 032010) 1025 1.4010) 01 0.0(10) Duta orrnged ss: M`Setaanndard deviation (Numofbvaelures included in calculation) +@ SSuuttiissttccallllyy siiggnaiffiiccaanntt ddiiffffeerreennccee ffiioommccoontnrtooll at at p< 0.05 byDunnettTabane p<0.05byDusfest. Dunnet test, . `Company Sanitized. Doss not contalnTSCA By | - H2:82D5a4y35S;tuRdeypeinatMeadl-eDoRsaetsDermal Toriciy DuPont 11574 TABLE 11 SUMMARY OF URINALYSIS VALUES FOR MALE RATS Group I Omg Group I 10 mgkg Group V 100mgke Group VII 1000 mg/kg VOL (mL) DAY 29 86 102 77 108 UOSM (mOsm) 7.6(10) 6310) 3910) 33010) DAY 29 1551 1235 1283 962@ 903(10) 511010) 328010) 284010) pH DAY 29 68 69 72 68 URO (BU/dL) 03(10) 0.610) 070) 05010) DAY 29 03 02 02 02 03(10) 0.0(10) 0.00) 0.0(10) UFLDUA(Yug2)9 148 174 192 39@ | UMTP (mg/dL) 400) 43010) 53(10) 12.110) DAY 29 m 6 61 34 67010) 28(10) 38010) 11010) Data arangedas: MSteaanndarddeviation (Number ofvalues includedincalculation) @* SStuattiissiiccaalllyy ssiiggnniiffiiccaanntt ddiiffffeerreennccee ffroomm ccoonnttrroollaat pp<< 00..0055 bbyyDDuunnnne'sttsTta.mbane-Dumnet es, `Company Saniized. Doss not contain TSCA Caf ~~ 4 | gz 8 2 BpE BdHadd Ed EgEd gg 8 3 BUY Iiig 2 - 3 2 g P23 g5 ds so gs : ne eo od i i zB 533 zf z 3 gi ji Fl El | Tid 28s sd ss 3 ii i Fives HER RE tH i g sz oz iix :4 P2 ooleEo bRaTnE d | i3 g i , SE Jib iSie |= d = BE a. o. Be! :3 181581 2 2 8s da =% as, e {BigP} o~ ge ge dA gna 8 i Cy dE g fiom BRE 3 f Zip i i 2 | iE | 1g8 EF gi ig | i183 322g | iid . {8% 5 Eo3 | |i iEMx g| | 15% si 2 S8 E } RHif!y f. giCo Ei RHIEEE, BLgn 3 i |P [Fo EBEEEOEiOE E BIiisE i5i3 i {i8f f1f g,e 7Fe37Fgz E2 geRH8E FpeiRYsidg 24 z& =~ 1 i5ieE 1 2 8 : g : fgirlm gr ca 5: HH i ' i fpr } 4 Eiagni 3 3 z Fi ii { Zing 8 mmenem is i E8 l| ly || i2= 3 gif EH gE ER | i iizg 5Q i1 ii 58Ine { = ' i i183 ~ 3g I : 0 sds i 3E |i . i5i1s] ! El fgg 8 ii ii 4 S8 g d8g.8ag A L1E42 iSlo B g p,PE SBEnE giaE enfC in Hif. H2o3f i gi gp o|e8 t AEBRErRgdBeEERn[5 Pd i2g BE 0 2% } HE 5a H"aE --_-- RE 25 | g 3 2 i 5i3 E4e et {3138.7 2. ae 1EkEcT g igiEn) 22 i idagn Zig iT-- a % i 8%l . an ow a3 E $i II a H zg o iiiigff i Tia i 35 i cEEE |i 3! zi : CE E g | ; i 2 4 EH 5 i 53 a || :; TfIy i 228 iihE at LiE c iiiEt a, 1i2E3 igEsE k g ia 32 1a git 2i i a8 . HEE 2 g | i Bfoii:: FB ? la; ii 1 lii p pS 8G8EhEEEes3f leBBEly5 EBERoE(dF gi iE faged @ i HL IE ELE lca 28 iat P PF EDEtERE p fedFgee [PH fon ~3 _ : 3: E21i82g7 22 ge on om | :3 i i 2 i580; i i Sig! orn] 3 | Fils | i S iRiaEE i : gPaT nTBB ie ii Si iT ia i el 200 i EgI i : izlod iii8sy : 88 ii i i: i 2EZ5Zl: | i 8 gi i 2i i ii1g4e3 & iH i$ daEE00; P ogi ig0% miiids i thd ZE0 a | ii EpsEEnoEfa Ei5 ifOiEEaY" : ggii i] ERg aEs i 8 4dide i! g 1| b jE EHH jHaEs iig3 2 i f gi{82 11p %. g feBEr ECEEY8 1id", 34 iBE P58EEER ik 1% =8] 2H8:D25a4y35S: RtepienuaMtaeldd-eDRoaystesDermal Toxicity -- DuPont 11574 FIGURES | | `CompanySanitized. Donotecontsain TSCA cB! - [HY Z Ped e H-25435; Repeated-DoseDermalToxicity 28Day Study in Malo Rats I~ DuPont11574 | APPENDICES I~ `Company Sanitized. Doos not containTSCACBI 1282.5D4a3y5:StRuedpyeiantMeadlDeoRsaetDsermalToxicity Duron 11574 | | I APPENDIX A | Individual Daily Applied Dose Volumes Company Saniized. Does not contain TSCA CBI i 8 i 2 4 ImIIIII Smmnozssas gessneases i i fap AEREREAEEEE CeCe ndRRdddnnd ii Tay BEER ORNS assdasediss Lo manmuszion snessense smmnssaios fap EEEGEEEER CORON daRRRaRRRd & FE i g ME INNIE INI RaREaRNdzEasEas iTop mEmEG RE RE 2. 38 & IJ,I emsmimmmimersimodn SginSasNeasSan gaesiaendeineianndys Ho3 Tul IRdRRRESER CTRNIIINED EEEREEEE i33 5.0 sSoindrneinmrmaanney onnamnmaaennaeInAeEr Ragin B amneevonce 8 SEYEIEIEEE 7 $EEELILLIE FEEEEELE mE 8 1: BIE 3 [te 3 I ;Byfrpo AgRmRmEmEeRmEeEnEnRn #: i 4 i2 B3a.2x :F iFiRdESdAsAsLdRaRsSs ~3 E | po EEEmE eens amma 8 5 F 3 | Ba saansitanscan aressmsnn FwRaAsRaRnRcAaRnAeRs !3 5f. ay RsRaAnRgRsEmRsEsReD: eaeadanaiil RFEisr5dRivdRainRees 5i Ei gfoesy JEA3RARGAERIRIEERMR 0 OARIIIENAIT IINIEIERA jd ify AERERENERR FRRERARARD . frp AmEERREEER CUUOTUOOT mesRmRnad iz i1aF; RERARRREER UUUUUUUTT RRAREREER i fab 2 manana 1g an --~ 2g 8 | = Lfan) mseansngeaanmaezaans 55 5 5 $2 iE IflRaE] EngREmaa | : - B5 aBu0; i@BZmEIiRRE:ER 3 ? it z $8 S:l Cae HEIEn : By SRRRANERBE i 2 3 =| F sEEsEaEEe z g 5 i fa smd CO Ramee i ff timmmenn Asdgasidn i i FE PWIE EEE EL 5977 i $3.8 disiiiidEd RRANEANED LIME ffl oo m mummnmn momen s adam saso aan . ff smEmmEmER COT Anasanedar i fap mRERRiEEE ceffnanan ggaARRRARsR i i 1.3 BEREEEE Tem Emma 24 G REEEEEagE . fazmssassr . gREEsRaase i ; i 38 z i ss InIILED 3 be 4333883588 i Bs 353A88588 z fap ssmeEEEnE Bal damndadan FF 2 PDgia ImsEnaRsIssEs s? 33 jig semen . i Be tesgmm ii PERE3 i#d2 5 oEcEsEeEsReEsRsLeCs 8 g3gsEses i ~~ i g 3 FH 4 i i i i 5 i i i 3 :Ia 4B.a8g SBI3SgIEtsEaRNIgEeEs AMNININIY 3EENEEER 2 BE pnp IED. RTOTIED I IIENR =& $ESE38EESE F Bhbsszzsiy 3 osressueess =? E 2 2 2 | i g 8 :: . 3S i 2 i 3 i i ol Li 29 8 ossgszpes #3 sisgsssias 2F8-2D5a43y5:StRuedpyeiantMeadl:eDoRsaeisDermal Tonicity l~ Dupont 11574 | APPENDIX B Individual Body Weights | Company Saniized. Does not contain TSCA Cay 33 3 : o% BENBNESIER EBRUEIEAIS DASERERRER ie ii z ie ~ Pro ommmm ommumn nanan 3 He i 23 . #9 : samstsnmsaonasnnnnsn posnaancaeo g EE 4 lo if bYoy mmm jTii. aHmEmEo 2 I Fo; gisEssEzsE Hil g3i2 i BEE =| # S8838IVEIL : 2 z i s? 2285D4a35y;StuRdeypeinatMeadl-eDaRsaetsDermal Toricity DuPont-11574 APPENDIX C --~ Individual Food Consumption || ~ Company Sanltized. Docs nt contain TSCA CBI -- Too H262-5D4a3y5:StuRdeypeinatMeadl-eDoRsaetsDermal Tonicity ~~ Individual Food Consumption SFoeondarCaaernnsy. TooraaadmCmoindee.y FloaYomdma/Cdoanssy. oo/cTsdamya/cdosnyn sale, 10 v/s srGmaram wa a Eizaslee 21203 2Fs0e.Hs2 GaGaens ndmasss Game sa aoolee pat 5wFosl 5 eoosli pt Gfwamims aaF3a oaol5i apEe3Yd 3w5d Nate, 11 10 w/v wSae dmss paiedie anB1se 2fm.e10 Grfaranrse sme0o GGwae ems0 5a32%e aiF2ex Fe] poii ee 3 rGfoesm Ba RX popyel mfoe3ed f3zrieed vale, v 100 wari ~~ wGhasmm EaeSs Ges ma w2o6e.e6 0s aon1in na p2S0ro7 fd faGaaswse mmaus3s Ge ma aa25e0 pred 55=3 pl B25E3 as GEeHS.ee frmeId =a 3a3 sate, vir 1000 a/ka wGeea aas0 2i6.s7 2F6.H0 mass GGGaeavee amhaa pr w=ae ped ffaeet0 a2a1 pd | PrfarrEes ace am EE pamisee] oi B6Exse8 Bp3ei Ex DuPont-11574 | |- `Coompanymp:Sanftizeq. DocsnotconTtsac icany Tar 2285-4D3a5y;StuRdeypeinatMeadl-eDoRsaetsDermal Toxicity DuPont11574 APPENDIX D Individual Clinical Observations and Mortality Records -- Company Sanitized. Does not containTSCA CBY ee &- 52.82-5D4a3y5:StuRdeypeinatMeadl-eDoRsaetsDermal Toxicity Dupont-11574 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY RECORDS EXPLANATORY NOTES CClliinniiccaall oobbsseerrvvaattiioonnss rreepcoorrtdeeddipnotshti-sdaopsipnegndairexnwoetreinrcelcuoderdd.ed duringbodyweight collection. | | - Company Sanitized. Doos not containTSCATE EE ] 53 g5 5 a 3zorii ofri 1F : Fi 2iEdi: | sf.E0da3fa5da%ia5iaFioasda%ia5d,a8i0n3cn i 1;oosLFt o. gd gokd fLtn v3d $8 iz ER] iz iz Br ? 3 iz: for3z fiz: fiz Bzy fiz fry 333 fas fi iy ie P051885% 5B:% d1g8:: fjgi:t d1i3:g ddld i 2g33ii *%f33g 1 g%33i1,.c%a31g i3 gg2i3a3ai gi2g 3t -z sPieilidgidgididgsietiidasdsiiidaciriiidnsigiins 53 Sireiiesiissiiasifasissi i ze 3 2 $ $ k Z23 i= . = = = = ~8 8 8 g 2 g 5 5 i 2 i3 33 3 ii | ii ii iidi %i 4f.05 2 s = 5 3: 5: sEiadaiadnalaaian i 1. . [I : 4: Ios SE odi dd | 8 i3 3 gs 3 | ] i: 1: fe 2d fa iPod id Poagd ragd ip ir gag bgid Eefbett P| fPlriligpiiieigirgiiiieiiiiiiigs : i Fleliledllisiici 85 i% 8 =4 5 3 ~ : i i i 3 a i 3 2 ii :z 3: iz i i rt : i 3 EE iP08 Sei.sfFao iadBaoiasitalnaifaoisa 5 Ti ogt gl gly it2 m Dori ogiioaiill gi: 38 fzd:8 i3g3:8 3P3p8p47%iio f8u% 3 ji i i5i:f PEiz tai jii: 5 iI g 2P3r3igE lfiiayE aRiefrt3I i3tiiaiiaigE iiaiilfe iiiitzg g 02 sPidltiidcsditdilgiitiiitiataielaytitiily ddrrlileeidesiiiiniesd . 2s 23 3 ls # ` 82 : 1 ig i= = z x A. 3: 8 i2 8 2 i 8iF3 38 a3 g i sElaisaSa.adasiaslanias gf 8838s | Pail 8 3% gi 3 gig 3 fs alg 8 3 " 3 Ep: ip Bg dy iy 1 {i Fofaiitfil eLg2E]daegi2tgdsii:d3 eii2 t: eii2 isy I edtREyEdliEggylitlgiifl diiiiin fpddlislpsgireicgicis 33 firsdidisiifsifiriesisis gz iE 35: 22 oo i H 2 5 PE - SoD LL B ~~ Z| 32 i: i : 2 i 2 i iz3i 2 { i: f. 8 i & 8 sg 8 2 = 8 | ziSaiadaiaialiadiaia L pIT ifog3 Egir ogdroagsd fla: 2: la: lis i fyps Sy: fpr fay Polis ais dss dss 3Poy2 lle 2die 2dd3a 200, 5Z pFiegitraigiiddreiaigdirniiiigsy g Jitigdiigdiiidiig i Prddcgddaidagiis Ss Pirsilseilssiccesi 325 i"tr ia - a j& 3 H 3 "da f.2 . . gal HE = = = ~ 8: || 3: 3 2 s a3 as a: ai a3 3 2 i4 & & iz PPisiiaeaiiataniaadasisaias Poy joi: 1811 1s 3: 1: 1: 1: | pli ph HERERO 8I 3or2i%g s8,83%: Ffq4 434g FEzi PFzi 3i3g% :f 28827 13 ig 3 foogaEpipiRgBaEgigiebggiaig gi8gEeifygaiigae Ilofhiitlibgigdyiybyargiiiirtiiairitiaitinatriii sf flrriililiEisiisiiilsdisd 1 ff HE I i I~ : 32 |3 5 i Posi 1k 1 : i i : EE f p. 3g 83 88 o 8ag, nm, odg, 0 3 , oa 0& 0g, i pE83adiidacRiRsRARIRARSRARR pies DDE IE EY RE 2080 82 32 Tu TEI IEE iid if #3 if if < | 8i 33433 Te3s3 Pe8s8 Pa8s8 F3ads3 i fgg fps fxs Epp dag 3Si oi3iPoi3aa 1i% fF 13a 4n 34 3F3aiw %i 1Po:g3o $iF1a i8wd. z fPripiididiitiadrggtiidrgifiigig.iiiigfg,t i sPP EE RR igitlI iig ilif iicqaitg iiisate igs i Pelldoseeiiogddesidasiiis 3 Sieesdlidesideciiesiiecil i i 4 ig | El C 2 EEis l g. gg zi 2 2 2: 2 $ :8 :i 58 :: .#.. ~ |3 |2 IEEERE | fidaandasdadiainaias ; 8 F 3 3d: dy igi dy ody : difg, 4i:f digy; 4i:i 418 #235 fy f3F f3 23% TofiErgiEgi Egiiicd El gdiyyiigiiigiiglly 2I4 FIiSsEdEiEiRsEiRiRsEiRfEiEsRiEiEgRiE 23 .. iz ig "3 E7E. s. g L gE o FE. g Vi E E Ls g8 i 8 : 2285-4D3a5y:StuRdeypeinstMeadl-eDoRsaetsDermal Tosicty --_ |i | Dupont11574 | b~ APPENDIX E | Individual Clinical Observations - Post-Dosing `Company Saniized. Doss notcontain TscA cay 21.82-5D4a3y5:StRuedpyeiantMeadl-eDoRsaetsDermal Toricity DuPont 11574 INDIVIDUAL CLINICAL OBSERVATIONS- POST-DOSING EXPLANATORY NOTES sCluibnsitcaanlceo.bseClrivnaitciaolnsobrseeprovratteidonisn trheicsoarpdpeedndduirxinwgebreodryecwoeridgehdtdcaoilllyecatftieornraermeonvoatloinfctluhdeedt.est Company Sanlized. Doss not contain TSCA CBI A| g 3 1 i % . i iF db ia 3 3 3 3d 3 ERE z iroF pi EE ain i PPP.iissiLitiedaidid E4R.i6d% adiIEaElEEs] 2 i A :3 ig i : 8 f 3 083 EY ! I is I I ji] Poagtligtag thigatadag! S| dfrsriiliesreilrniariniisispeirriieees 3s) PRRRiBEipiifegiifisiicd | ig <3 3 a9 5. is i= 2 - - = = & & & - Sl = == - 8 B 3 X 35 i 5 i Tioidsi 1iiEk 1i iioaiir fit f E:I0aS3a8302300 x 2 1 31 i FE ' i ig P g d$ Pho bhh i piirdatlldi BEReREt RE [EEESERFERERRER) Preffefifiablie: ofipbniiliee 2 IERIEEE RERERREERRERREERREERREEE [J . := ~ o 8 |2 5i i ii i H io .f 2 3io5 oii gi 3g pd 3 3 5h 3 iIs7 $o1F8 853 dEEiy ii 2 oTLod4 $y E } IE 43 FIER 3i, 2 frida ff. .33kA8. 03330358 2 i111: 11 iid Pov: i Sohn odr ba by bs bs Boass,fitgoeffiidpFifasigrdliciiiiiiisiyieaiigriliiifastgigldiy;. i Jfiiacdibaecdiaitiaredigiiiidtgaaatiiiieiendy S| fagsisppissiiiioaeiiegy g Sy CPisHERtR8 I8IIR.iRR% RII2 RI.IEEEEEGRI].GLfGu 33 ogidg ii 2 :t #4 HE a 2I 8 P. E .. 5 5 - - Ai g i3 . E3 11 3 4 1 4 7,01537 81 11 {ia 3 EERE RE REREEIR 1 3 { 5 3 o 2 Phubuhnhhy P11 1i 13 g ; 3 3 3 11d ibg 3 z1401 3 Z 3 I| jireprrpiafeeges g Poff gRigEiEEc Et 1 frERfEEsEREREs 313% i 33 g 3i 32 3g #8... LL. N: 5 | a 5 3 i 3$2301= 5 i3 2 38 i5F% i5s3 gd3 i3 iF i: id i i 3 . i 3z 3 FpE3i3i.ii5Filiiiies.iLiu zdazbilibiiceal:, i 3 Pb hhh Ty S11 3 i8 Fg i3 g i Fi 2 33 F3E : FR ig EE] 3 Toeiladrairiiaglsadagifgg iEiiigti i afd R aaiy Erriraissbiioriireiiitd :13 E SP lE epH laEEgI lpgR ii$ iI p9e5 ti3i e78 s%i gia id 33 FIEEEEEREET EINE Fo: 8 & gl i. . . i3 i= = = iE .- == z E 3 sr 3 kl8 i 5 d s3 14 iiFp sir r5i%:i <1 PEIIILiiriiiiaii i : . i; 1 i713 2 i3d% i or 1f d3 PPor oEF,REgEi, IRF0R%fi NE15jN185E03 . I 5 E8R48 E5RLE55R%R5E8EEE55 ER:EE3 freiiesisiizis F388 5485848 - I d FiiIRfEfRiRfEiRiRiEiEtRiRiEg! a2 8 Do ~3 . : 8 zz i i if Fd y 3 3%i3i i 3 Poi, ii ing i 2 || Sh d3 esfida i3E: 13%334 ii 4 i FFL Fihr3.7d7a8s7e03i3l%a8dansidadidnai4 f i !i : fT 11 LI | id [E Dagliflegtigatigaeg ad Poi jag gr gigi i EiAT8E;F;I 8EiA8EsEdE8AsE8f2F;34E4T;E Ereiiifseiessisioiosi & shes bbd i todo I Pai iiceife iia iii 24 Fries liiaagaaagaiiaiy 53 ie FH to: i: it Ed EI HI Lo Lo 3 85 5 B B = gz HES == =x ~~ 1g : 8 1 g 8 3 : i id. . i i 2 FE 8 > 8 8 ii. iid :: iiiy iia i3 i: is 3 ii ii i PB.riiF3Ffeds5i3iasi%iiydilai3als aasi1Fidei04%eii2ii2., g 4 i f t Sy 1 a 3 3 3 i s Pk F f d i i i| | oiling iiieegiiee FiI in 7bb3 h5 y h 3 h3 ToafEieif fes griiiifdgdiss aiggadiliig aaigd easl 2 Pris EicTiiiiEiiriiiie 1 FFaEbiiiairdbiairbirbiitiigiibiiibiiiibcEs 32 FE3iE3384833 PE iii438 Moly ss iE os... s : . . 2H82-5D4a3y5S:tuRdeypeinatMeadl-eDoRsaetsDermal Toriciy = DuPont 11574 | APPENDIX F | Individual Edema and Erythema Scores . | `Comoany Saniized. Doos not contain TSCA CBI -= 2H82-5D4a3y5:StuRdeypeinatMeadl-eDoRsaetsDermal Tonicity --_ Duponi-11574 INDIVIDUAL EDEMA AND ERYTHEMA SCORES EXPLANATORY NOTES DRAIZE' SCALE FOR SCORING SKIN IRRITATION | Evaluationof SkinReactions Score Erythema and eschar formation: INO IYER vss: 0 VR ery slight erythema (barelyY DErceptible)..........r, nnmnrenrnrmreemn 1 (VSl1ig)ht) MOGEIRE 10 SEVETE EXYICMIA rss 3 (Moderate) Severe erythema (beet redness)toslight eschar formation (injuries in depth)......... 4 (Severe) Edema formation: NO CUA crs: 0 Very slight edema (barely PErceptible)...........rvrvrrrmmrerremrirmire | (Slight) Slight edema (edgesofarea well defined by definite TISING) ....ovrvrvrrve 2 (Mild) Moderate edema (raised PPOXITAtely 1.0TI) veneers 3 (Moderate) | Severe edema (raised more than 1.0 mm extending beyond the area of exposure). 4 (Severe) | a EDdritiozriea,Jl.CH,om"mDeirtmaolfTtohxeicAitsy.s"ociaotfFiooond and Drug Official ofthe Urited Stacs, Austin, Texas, The 1959, Pp. 46:59. Company Saniizad. Does not contain TSCA CB ~ : i: i: i | i: 5 FE ; & i: cccecccsce cesceccccs cosccsccss = LIE - . i3 0H1 oda2 :i :z EE 233388883 7 I3LPLEsgE sseEEeEsy  : i:a 2es0s000ss gp i i: pp g i 1 : | : y Z g wsevasesas aeevoesves veevasnias 2 14 i i: Bi; i1: cococecces ceocoscose sosccccson il: f i : seeeceecee ccccscsccon seeeneeces ig g : ~ i: i: 3&8 lm F18i1s . 5 i; occccscesce il: ITT 3 EB - Z& a Foceccnnees FE 2 sereLeessy : i 5 : : i "og3 z3 2 ; i i } i :i i i i} f 1: cooseoeeee coccococon cooccccocs } Hoi 33 4 : : cocJccoc cccss sccs s &c cosce eccss cce ~ : E g 3 1 5os 8 i i i : if: Ci eeeeeeees iE i: . & 38 god 3 (* HE <3 3i - | EX gggysgvesy C3 | 5 f1 cesovcccos asooe : : | ii :3 eeessesece eocosccose eoceccoccon i I.; cococcccoe EE ceccsces !] }i : ecocccccse cccocooccoe oo ' ili; -i} | i.: occccccsces ococcccsce cocceccecos % ]i 3Io ceeesesees cococcecce en |: esccccccne ceeoeereee cccccccoso HA 3 5 fa eeeccocces iz Pi Pi i. HE iis i ii . gif Hs iii sccoscsscs cecoceccco Fa z fo eeeeccoces A FE : | IP Hii. Bool 3:2 . 7 cocccccane =& [Rtttitttit] E 3 i 3 2 g 8 B : - : ]: Ja cocecccses cccocenen cocccsssos i5 :! sococcoson Ji eccescescs fa oewoosns ecccccce sasovrsace odf viesesss i noE8 13 crores corres cone il: oc i gis ceccee EN Co i Jz cocccccece coccccccos o ! :' 5 cccsccconos z fz woossessss seccences eee ] : :! 33 eccocccces ai 3 1 esssessses ii Bi fr cooccceccce Bi 2 fz ceccccncan Fin EE eococcccee iis fu cocccccocccs I 5 cocccscccs g I : Hoi Bl bi, FE 12 cocenoeces 2& ggggsessnes ig i z t : ' .  i 2 & i 3 t .: 1 : i iiii : Pz Ps ' i i cocecoccce cccccccsce sssscscec ig kf : Hootie : i 3 i eaEamanan: . sszsanzne ; sesmpnEnE: lm : | 2 5 ] i y i ir ! i fa cccccccsss Is cocoomooee PE Hoh io: CE i, HH . fr eeeeeeene | F2-82-5D4a3y5:StuRdeypeinatMeadl-eDoRsaetsDermal Toxicity DuPons-11574 APPENDIX G Individual Blood Fluorine Levels | |~ | Camnany Sanitized. Dass i cantain TSCA CBI | 102 2812D5a43y5S:tuRdyeinpMaeleaRtaseDedrm-alDTooxiscitey BLOOD FLUORINE LEVELS TEST DAY 21 Animal Number 665732 665733 665734 665735 665736 Grow 1 I I 1 1 Dosage (mgkedsy) 0 0 0 0 0 Fluorine (ppm) <0.5* <0.5 <0.5 <0.5 <0.5 665742 m 666655774434 mn 665745 m 665746 m 10 5.96 1100 <00957 10 0.52 10 <0.5 r-- 665752 v 665753 v 665754 v 665755 v 665756 v 100 0.78 100 0.57 100 0.54 100 0.66 100 0.6 665762 vi 1000 1.24 665763 VII 1000 <05 665764 VII 1000 <05 665765 vi 1000 122 665766 vi 1000 1.38 - a <0.is belowhe limitofquantification . Dupont11574 Sl --_------ | ~~ | Company Sanitized. Does net containTSCA CBY | | 1252-5D4a3y5:StuRdeypeatMeadl-eDoRsatesDermal Toxicity --~ Dupont 11574 -- APPENDIX H Individual Animal Clinical Pathology Data |- Company Sanlized. Doos net contain 75 cay Te 2H8:-25D4a3y5S:tuRdeypeinatMeadl-eDoRsaetsDermal Toxicity DuPont-11574 ~~ INDIVIDUAL ANIMAL CLINICAL PATHOLOGY DATA EXPLANATORY NOTES sessmvunsions: peoma.1 ahodtequtaatkeen or not performed OBGOvk D CgfiaimmpaiinaacroornnodrviaelislouenftiBcYiefnosr tfoersttiengnting To Toatvoifdruminl Hemastaomlpolneycvoanldp uietsi:ont 6BBG5EG DC hmheeemmmnesgdoiScocrrhipitunscular volume wFFiooeii D SSroaiidneCClotrupdutissceturirisbruthReiesoeinsotwihiodibtinhn concancration AwBFeiT 1 DpBlaiEcceSiisaHt cSfeocIuincTuioocoruemsecome JAAirEm Sdbheesoiuuttee mleyumtprhoopchyitte (ald forma) po eEAeCDidiiboeelciiueteeeTSbaarseoiepshimelacasned cent TadivwRidogumnl 2+D0dnGBollroomooadylrCooslslsMorphology Values: ihfiaYee T lmpioovrooereaesl:ia wBAoeii 1 FeStcphatinmnieoaryinteeisss Te fume cite 57 CToRvelEi-dEely Sboodyc exantned: see whole blood sample condition IndivoidumSsil WaitHSeeurFsmleaoodwhCiotiel / Platelet blood cells Morphology Values: FRoBgyD a rSheephbotdiiesCiropniasn . 5G6B5C1C1 BpblaaescscoaineirriieccuruStrsoieopieemscinste B TL r GR.Roc examined: see whole blood sample condition omyany Saniized. Doss notcontain Tea ogy - ws 2182D5a43y5:StuRdeypiensMteadl-eDRoastesDermal Tricity Dupont11574 ~~ INDIVIDUAL ANIMAL CLINICAL PATHOLOGY DATA EXPLANATORY NOTES (Continued) Asmsvarious: (conesoued) Individual Cutnical chemtatry vases: FSMhprrr g1 AsSyeeparrEraletietpe]elmnisenltoarrasnaantsetrearsssse 2HoSxEmn 1 SLSehrEamiicnnoerEahsDomrvpTanzaotgaesnease Seen nitopen aS5Xm8C1|1 hSSCiaeatEndvetaeerninses aSR 11 ssaSaielaednporetn SinsEDD spSoreorraaosusnitcm prosperous ~~ FC mEiRn E i plasma hesor lyats rok sblast sae mpleoeforafrd luoeriSdetdeemtermainratteion adiviaesns Oeinatyets viasees:s coton) Waw Bu C11 CSUHrhionaehIeosmEsianRiey cae cectprocs of che myarosen ion concencestion oo ir Thien wBwhoh 1 1 iburebestiiwnoagnenes weoT1 UUrEiRnSe pieuoiveeidese IndivDsidoructal U1rinpEeiinMeincutxnoiaseceobtpeatnsimssacmeinnatcsion Values: || . aWRcDD1 iihmoierneartgecaayiebeeieeestss sells . | nD em | |~ | | --_-- | "ompany Sanltized. Doss not contain TSCA CBI Tw: 2182-5D4a3y5;SRtepiuenaMdtaeldy-eDoRsaetDsermal Toricity DuPont 11574 INDIVIDUAL ANIMAL CLINICAL PATHOLOGY DATA EXPLANATORY NOTES (Continued) WohtehneriTnedaisvoindsu.allaLnisoaflwhdiactha sarree cnoutplraeiproerdteidn, thiet msatyudyberdeucosretso one of the following reasons or tthhVeerAesTaAmwpalseepiuwntastsuticciolcuoiltedtnetdnots(acmbupeoml)aebtfeoirnetae.st(iAng) (aS) tTh0hee'aaaanmafpmirpeailewadvaslsedanvoaptirlioasrbulietvoabflsoearmTpfelosertoitntegsitsic(ntWgRi)on eWphoaerntoEamonerdtanondnyivcihdaauliaclultaohtbeisoernresvcaotprideoerndforvvaealseuder.veictohxTodrethdaetaxsamBpIblLeeLi,nRgUbALlfNesbsidalcitarh.uabnina caesrtarienporvatleude,aeca<0l.c3u,lat0i.o03nswavsere ~~ ~~ Company Sanitized. Dos nol contain TSCACBY | ET : : 3 2 : : : PIR HELEFELE LET PS EEE i nBinEingsndinEa EBahRdusinibnil i JE BHDEN mnnEm Z Pi E Emm mmm :3 Be EEEAEAE AREAL 80 3EREIEAEE FRssdEiaEE 0 EsEEEERd EI z 88. IEINIINNGE Coin i34 Bgyd oip R23ngsdzNz3EasNe po eusReEnRasIiNaEs 3 I : i: . ssssssssss ; sEEEsEssss 3] 2 2 4% 35 gezssnaass & grprrnees gf 3%szssgsss gRgInsIsey BF zidsddeddd ddssssssds 2* nsovsen,es eswademsas LR EEERREEFIEEE ERE HEED mnDEn Fy mnmmn nnnEs i Poe HnEBE EnmED: d iidgsacdis ssasasanss ge SgIIINEID mmm | ses osmmmaes = a f t35 dirg. ammTet a 33 2 13 3 , BEEETEEEBY 3 3 sol ay Cgmrmesraes }oanmnimms . 2 umn x po FEBEBEEEEY 3 osmpmssiine 8 2 & i } g g : f 3 i i 3 i : i EeaEaEnNsEaaEnEeEe mmm ensggsnzse TE numnm mann nunnn nnEmn i| joanna ii &2 g esn nataanen i7 i tensgeanen 332 8d 7 ssgszsssas | susssarssy I= 7%. SAAAAGNSAT BO AASEGSEAE | 22 i fagsssise g Ieesssses : 2 8 i i ; = EI Ea 1 8 4854833533 85%3%aIaAN 2 2495A%BRAS RARRANAAAR P| Homma 4 8d : LTTLE] : vEazRaasey | Hq ! EHR i gezpsezses | ~z 5 : g ' i % 3 2 Le fies fpf : dFo RE ' i Be, 88 ie pares ates ! 3 Ty jm pn 2 a5 i: |2 P = I sesss;sgmsmessssesese 11 SEESERERER aeEEENEES  i 8 2 35 Eee 2 i p1oaed EjEE Hi E eenRgBRE e ae BEER i8 A Pr is HHmEn BuHaEn | Bog Bo a : 2222828828228 8 gze2008808 | = 3= g 3 g 3 3 3 ! i iis ere Cee oC : 3 : : i PC ppmes ;BEpsgepegeEss Su Demmne |r  2 2 5 zg : 3 i i ! i i i5 | a3 : i | s} umEmoa;REEEsEREEedeed i FRITHH HER HE | | |2 : $f swssavsses szsaveazey i # smmmn mhwnn i 8] sxzavanzan maswanzass i ba pom momen n 18 ssasaaaass neRsRRERR fn nmmpam unEEd : 1 iu F3usuneTAs ReRRLROARL is EEEEEEREEH 33323392382 ou, EnERRnRmENRNENNNE . 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B i Po ! igpiEaidf f53 g5: o i ma 2 ie guens ges az) | idddeaienas aii TT jp EEEEEE i id | a3 imme. 1 Pama a 1 ia jessdssdase 80 : i L: . i i i 2 Eo i HE ip E iasiagnn aad ani :< i 2 svesss gal |L _isgazp aasasz aAgi A i pmmmE az giz jssssesesss i : 3 La | : 8 : i 1 1 & Tfo h |i ; HEHE E 4 id 20 i EE i a g Fe pispo seifal sieeg gal g giesstitEE 2 i : Eom 2 Le isgpnshusss ug) i5 yfiegBAiEpEsEsEsInEnEnEsE sBlE 4 pire 38 Sy isczeseseer 8 23 i i 5 i 8 - H25435: Repeated-Dose Dermal Toxicity 28-Day Study in Male Rats -- DuPont-11574 --~ APPENDIX J Individual Animal Pathology Data | --_~ -- rr ----------------------Com-- pany-- --San--i-- tiz-- ed.--D--oe-- s nrot-- ceonta-- min eT-- SCmA CBI Time 2285-4D3ay5;StuRdeypeinatMeadlDeoRsaetsDermal Tosicty -- -- IINNDDIIVVIIPDUUAALLAANNIIMMAALLPPAATTHHOOLLOOGGYYDDAATTAA Dupont 11574 =~ KEY TO APPENDIX sas1on cuonia: oSeHipCsrAtoEeoppLraiCts:hcoels,TougceyhfaGScaah"llaefnoucgceutsals,esariengmunledtdeeisafcaosrtcieabsnleo,diloftoavciscioosnrssdui,engvuntoiollvatethemereainlt;m)oBripLelh:aotlieonrgdaiilcs:acceshsvae,r.acWtheaerr,ssodSvpiepsvrtiorcbiyrbisustetiveoernr banyLdf WODOL: azo WOBATE: SEVERE: TThoeteaslnoYuitmionf change present barely exceeds that Which ia considered to be within FIrnogbeanLeiryald,escheotlepsrioodnucies aeansyilSyincltdieonncsiifissodpabtuitmeonft.limited severity. Tha lesion TLhieRsclaedsioCnhasisee"porromionregnatn bduytsfucnhcetreionis15igpnosistiibloen potential for increased severity. Theydegroes rof chatnegentfoo0eitehecrtasofcoonmtpsltetaonssacvonosnideorxedexpoonssiSbylsefunoirtgiroenat enough SGirades sienisial clhreouggh sevTeerle ceTperosentTproge ressivTeerimclveSnesnt sSehveerSityTaloEng a contimium vith --_ He atten on wei GSroessnobnseervations Listingo multipmitlese sasses for a tissue ave distinogeuished vith letters (i.e., A, | || _T ------ ThT Company Sanflized. Pos nt contain TSCA CBI 2182-5D4a3y5:StuRdeypeinatMeadl-eDoRsaetsDermal Toricity -- Individual Animal sashology Daca Dose Group 1 0 sake sex: wales Radeai wat Hicroscopis wacroscopie Findings ses732 RToeTtreemdlin$o5nSDSuelyfen+ara'3io3etsitcrom I necropsy Gross sathotosy Wo MaLcivraons,copKiIc SAb,mormTaHtIiGcHySObGsweerv,edkan, TEETH Hstepathotony WRATOPOIESIS, BTRMEDLLARY, minisal. Wo MiKcibrvoEsvcSo,ptRc OAbHmoSrsaGiLic,y OSbsKer,veTdE+RT asm TTKeoirnlmaiilnal5e3nsobafcyfrnieiac5ec3ee trom necropey Gross pathology Wo MaLcivzeona.copFtciAmm,oraTaettshecytooSbsueerv,edska, TERT -- ~~ BATOROTESIS, BXTRUGNLLARY, sinisal. 665733 Continued on'E She mr e Bae on ---- Duport-11574 --~ -- ee Company Sanitized. Doo not contain TSCA CBI ms F28--2D5a4y35:StudRyepienatMeadl-eDoRsaetsDermal Toxicity Sndividual Animal Satholosy Data Dose Grow: 1 0 ma/kg sex: tales nial Rat Microscopie & Macroscopic Findings pr Continued fron previous page Hstopatholony Mo Mi"TcRrVoRsOcToDpiGLcANADb,norSmKIaNl,ityTEOEbTsHerved ses Tioirisiiendalon sDaacryif+ ic3e9 Rninl {6 signed oft trom necropsy Gross sachology Yo Ma"LcErVoEsR,copFiIcNEAbSm,orTmHaYlRiOtIyDoGbsLeArDv,edSKIN, TEETH Histopathology : FIEFGLTOBRTOIIEOSNT,S, SEUXBTARCAUMTEED/CUHLRLOANRIYC,,siFnOiCeAaLi,. mininal. NEGHROPATIY, CHRONIC PROGRESSIVE, minimal. Ho Mi"TcRrVoRsOcToDpiGLeANADb,aomSmKIaNl,itTyEOEbTsHerved assis --_ TiAneeirnm"ailnealinssDsaiacgrynietdic0eoft rom necropsy ross pacholosy Ho vaLcEVrEoRs,copKiIcNEAYbSn,orTmaHlRiOtLyDOGbLsAeNrDv,edSKON, TEETH 665735 Continued on the hext page -o: DuPont 11574 ~~ `Company Sanitized. Dos not contain TSCA CBI | 136- | H-25435: Repeated-DoseDermalToxicity 28-Day Study in Male Rats ~ Inatvidunl Anteal Pathology Data Dose Group + 1 0 sg/kg Sex: Males Animal Ref | Microscopic & Macroscopic Findings 65735 Continued from previous page [re---- `IaNFrLoOpBoArTeIsOtNs,,`SBUXBTARCMUTEEN/LCLHRAGRNYI,C,mFiOnCAiLs, minieal. No MiKcEorNoEsYcSo,picTYARbnOoSrmaGLlAiNtDy,obSKsIeNr,veTdEETH sess TnKeiirlnalieandaloSsnsDasacirybinte+dic2e9ote from necropsy Gross pacholoay + No M"aLcErVoEsR,copFiIcNEAYbSn,orTmHaYlRiOtIyDOGbsLeArDv,edSKIN, THE Histopathology : wowH`sNEENCA+HTROOPBOATTEISYI,S,CHREOXTVRIACMEPDRUOLGLRAERSYS,IVEm,inimmianli.sal. ~ Fo Mi"cTrRosOcDopiGcLAADb,norSmKIaNl,itTyEEOTbHserved DuPout-11574 3 ~~ : Company Sanifiznd, Moos nat cantain TSCA CBI iT | 112555:eRrep:DosoDosr Toxic _ mrss ws. sig a sE sp 5o siep ] BE EPTa H cn wenn anon reoseiE R n EL TSSes, ee sion nE oonera ,e seaT. ,Site. --_ T Fazr27aA J--IEEAT SR kn, ree simepuiniont ~- SRoE nsTgrTamRs vEaE inn cs cnn on ro Duress | || ~ || . oonCompany Sanitized. Doss not contain TSCA CBI H2:82-5D4a3y5S;tuRdeypeinatMeadl-eDoRsaetsDermal Toxicity PS Individual Animal Pathology Data Dose Group + 1 0 sak sex: ales nial Rat Microscopie & Macroscopic Findings Ge Continued from previous pede tetopatholosy Ho MiKcIrDNoEsYcSo,picTHAYbRnOoIrDmGalLiAtDy,obSKsIeNr,veTdEE:TH sess nTKeiirlnmlieandaloinssasDcairyginfe+idc2eo9ff from necropsy Gross Pathology + Ho MaLcEVrEoRs,copKlIeDNEAYbSn,orTsaRlOiyLOGbsLeArDv,edSK:IN, TEETH [r--_ vemMHARCARTOOPPHOITGEESSI,S,PIGEMXETNRTMEED,GLLFOACRAYL,, miinniismaall. KeowWIsNEFAL+RAOGPGAATTIYO,N, CH`RSOUANCIOCTEP/RCOHGRRCENSISCI,VE,POCmAiLn,immailnimal. Ho Mi"TcHrIoRsOcRoDpiGeLAADb,noSrKmIaNl,itEy EobTserved --_ assra0 TKAeniri1ssiiaenldaliesnsDasaciyrginfe+dic3eo9ff rom necropsy axons pashotogy : 665740 ContinueHdoonM"aLtcIhrVeoEsR,hceoxpF:iIDcKpEAaYgbSem,orTmHaYlRiOcIyDOGbsLeArDv,edSKIN, TESTH DuPont 11574 || `Company Sanitized. Does not contain TSCA CB! | 1 H2-82-5D4a3y5S:tuRdeypienatMeadl-eDoRsaetsDermal Tonicity -- Indsvidunt Anisad pachotoay Daca Dose Group : 10 mg/kg Sex: vales Sinai Ret Wicrousopic & macroscopic Findings pre Continued trom previoss page Histopatholony + oSNHEEPMHA+RTOOPPAOTIHEYS,IS,CHREOXTNRIACMEPDRUOLGLRAERSYS,IVEm,inwiimnailsal. %o Microscopic semorsssicy Gogerved ses TKReiarTimTnieandalasnsusBcairyginte+idc3eo5tt from necropsy Goss pathotosy Ho MLaEcVrEoRs,copKiEcNEANbSn,ormTaRlIiRtOyIDoGbLsAeNrDv,ed`SKIN, TEETH -- HTERMFALTVORPAOTIIEOSNI,S, SUERXRTCROAMTEED/CUHLRLOANRIYC,, miPnOiGmALa,l. mininal. --_ Ho Mi`Kciroowsecrso,picTHAYbRnOoIrDmGaLlAiNtDy,oSbKsIeNr,veTdERTH Dupont11574 |~ Company Sanitized. Does not contain TSCA CBI - H2-82D5a43y5:StRuedpyeisntMeadl-eDoRsaetDsermal Toxicity --~ Individual Animal Pathology Data Dose Group + 15K 10 mg/kg sex: Males Sninad Rat Wicroscopie Macroscopic Findings p= nTKeiirTnmTieanda'lon0saSBcairygni+efai'c3o9ete eron necropsy Gross vachelony + Ho Macroscopic Abnormalicy observed + ser TAKeinrlimlmieandalo5nsDaouciyrginfe+idc'3eo9te trom necropey Grose pathology Ho Macroscopic Abnormality observed ses TTAenerimmdianlaleinsSsBaaicygrnief+di3c9eote from necropey Gross Pachotogy Ho Macroscopic Abnormality observed casnas. --~ TAKeinrlimlieandal5o0nsDsaiacgrynief+dic3eo9ff from necropsy Grose pathology + No MaLIcVrEoRs,copKiADcNEATbSn,ormTaIlRiRtOyIDoGbsLeArDv,edSK:IN, THETH DuPont11574 Company Sanitized. Doss rot cortain TSCA CBI - H-25435: Repeated-Dose Dermal Toxicity BR eicenmimidsimiotmmmmmmmibomeeoeDeEeCnUeSe, Individual Animal Pathology Data Dose Group : III 10 mg/kg sex: Males Sninad Rat icrosaopic i Macroscopic Findings Gnas TnKeiirimniieanda'leonSDasaciryginfe+dic2e9off from necropsy Grose Pachology + No MaLcirvois,copKiIcDNEAYbSm,orTsHaIlRiOcIyDcGhLsAeNrDv,edSKON, TEETH sssar TAKe{mriisTnieandal`{enssiDagacrynie+fdic3e0ot from necropsy Gross Pacholoy + Ho M"aLcErVoEsR,copRiIcEYAbSn,ormTaHlYiRtOyIDoGbLsAeNrDv,edSKIN, TEETH sesre TnKeiirlemliedndaloinssDsaaicygeni:etdi3c5oeft trom necropey Gross satnolony Ho MaLcivrions,copKiIcDNEAYbSn,orTmHaIlRiOtIyDoGbsLeArMv,edSKIN, TEETH sess --~ TiRaeiirinmiaielndal"iesnsDasaciryginfe+dic3e9off from necropsy Gross satholosy Yo MaLcIVrEoRs,copIiVcEASbn,ormTaHlYiRtOyIDbGsLsArNvD,edSKIN, TEETH i -- Company Sanitized. Does not contain TSCA CBI Taz: H-25435: Repeated-DoseDermal Toxicity 28-Day Study in Male Rats --~ Inatvidual Anieal pathology Data Dose Group: 111 10 mg/kg sex: Males Animal Raf Microscopic & Macroscopic Findings sess TAKenirilmnliaenldaloisnsasDcairygin:feidc2oe9ff from necropsy ross pathology + Ho NaLcivzaons,copKiIeDNEAYbSm,orTmHaYlRiOtyIDObGsLeArDv,edSKIN, TEETH sess ATKeinrlimliesndalo{nssiDagacryniet+dic3oo9te from necropsy axoss pachology : Ho MaLcivreons,copKiIcNFAImSo,rmTaHlYiRtOyIDObGsLeArDv,edSKIN, TEETH --~ DuPont-11574 ~~ Company Sanitized. Does not cain TSCA CBI -uw. H2:-2D5a4y35S;tuRdeypeinatMeadl-eDoRsaetsDermal Toricity Dupont 11574 --~ Individual Antaa) Fachelogy Sata Dose Grow + V 100 ma/ks sex: ales _ sainad Ret Wicroncopic & Macrossopic Findings GomszaermiAKinniiTmaeadd"oCnn"ssDaicagrynietdi3c5eote fron necropsy axons pathotosy Ho MaLcivreons,copRiIcEASb,ormTaRlYiRcGyHDoGbsNeDr,vedS:KIN, TEETH sess TAKeiirlmnlieandalo1nssDasaciryginfe:idc3e5oft from necropay Gross pathology WoMacrovsceopnic,FibAebrmso,rsTaloitcyocoSsier,vedsk, TET aasrse nTKieilrnlmaei?dnal$o8nsBasaciyrginteidc3o3ett fron necropsy ross pathotoay : Taian, Brute, sila. ~ no Mavcaenos,coKpiIcNEmLSo,rsTmHcROy cGosiearv,edSK+IN, 65754 continued on the next page |~ `Company Sanitized. Does not contain TSCA CBI a -- F2-82-5D4a3y5S;tuRdeypeinatMeadl-eDoRsaetsDermal Tonicity DuPont11574 --~ Ingividual aninsd Pathology Data Dose Grow : V 100 sasha sex: wales Aina ef Hleroscopie & Macroscopic Findings -- Gara Continued fron previous pave Tr [re---- Wo ICROSCOPIC EVIDENCE OF MACROSCOPIC PINDING. No Microscopic Abnormality Observed assrss TAKeiirlsnlieanda)on5sDoclarfyinteidc3e5ott from necropsy ross pathology Ho MaLcivraons,copFiIcTASm,ommTaHiYiRtOyIDobGsAeRrDv,edSK:IN, TEETH ass TKReoirtmteialnalon5saBScairrnief:aic2c5eee trom nocropay Grons patholosy an,Hi ThRom kDGLAN, D,sax, TEETH --~ sesnsr KRTeariimnianeal$5dssaicygenietdi5coe e tren neczopey Gross satholony Wo Macroscopic Abmommalicy observed | --~ _-- Company Sanitized. Does not contain TSCA CBY EE 2H-82D5a43y5S:tuRdyeinpMaeleaRtaieDs eda-lDTooxisciety ~~ Individual Anisad Pathology Data Dose Group + V 100 my/kg Sex: Hales Aainal Ra Wicrascopic Macroscopic Findings ase TAenrimmiaodnlaloisnesDairygni+ede2o9ff from necropey Gross patholosy No Macroscopic Abnormality observed Sessa TKAaeilr1amiaielndaloinsssBaaicygrnief+dic3eo0f zom necropsy Gross sacholony Ho MLaicvrions,copKiIDcNEAIbSn,ormTaHlYiRtOyIDCbGsLeArDv,edSKIN, TEETH ses760 TTAenirimemiadnlaliosnsDasaciryginfe+idc2eo9ft trom necropsy ross pachology DILATATION, QNILATERAL. Ho MaEicroscopte Abnormality Gbsesr,rved 865760 Continued on the next page ... DuPont-11574 | Company Sanitizad. Does not contain TSCA CBI | Te H2-82-5D4a3y5S:tuRdeypeinatMeadl-eDoRsaetsDermal Toxicity --~ Individual Animal Pathology Date Dose Group + V 100 g/kg sex: Males Animal Ret icroscopic & Macroscopic Findings esas Continued from previous pase iaopatholosy oweDsILATATION, PELVIS, UNILATERAL, mild. seser nTKieilraimeldinoinsDsaiacgyrnief+dic3e9off fron necropey ross pathology No MaLcIVrEoRs,copKiIcDNEAYbSn,ormTaRlYiRtOyIDOGbsLeArDv,edSKON, TEETH DuPont-11574 --~ Company Sanitized. Doss not contain TSCA CBI --- we 28H--2D5a4y35S:tuRdeypieantMeadl-eDRoastesDermal Toxicity ~~ Individual Animal Pathology Data Dose Group + VIL 1000 saky Sex wales Anina net Microscopic acroscople Findings wwe TKAneiirlmmlaielndal`ionsDaaaciyrginte1dic3e9oft xom necropsy Grose patholosy Ho Ma"cLrEoVs,copFiIcORAEm,ormTaHlViRtOIyDOGbLsAeNrDv,edSKIN, TEETH Histopatholosy veTWENMFMLOORAOTTISOSNI,S,SUEBXATCROATMEE/DUCLHLRAORNYI,C,miFOnCiAsLa,l minisal. No Mi`KcEroowsEcvSo,piTcHAYbRmOIoDrmGaiLiAcy,oSbKsIeNr,veTdEETH ss763 nTKieilrnlaeatdnaon8sDiaacfyrnie+tai2co9ete tron necropsy ross Bathology Ho M"aLcIrVoERs,coKpiIcNEAImSo,rmTalRiOtyDobGsLeArDv,edSKIN, TEETH tstopathology --~ veBIANTFOLRAOTIIEOSNIS,,SUEBXATCRUATMEE/DCUHLRLOANRIYE,, miFnOiCeAaLl,. minieal. 565763 Continued on the next page: DuPont-11574 | Company Sanitized. Dos not contain TSCA CBI | Tass H2-82-5D4a3y5S:tuRdeypeinatMeadl-eDRoastesDermalToxicity ~~ Individual Animal Pathology Data Dose Group: VIX 1000 mg/kg Sex: Males Anical rar Microscopic & Maseescopie Findings sess Continued trom previous page Histopathology `NEOHROPATIY, CHRONIC PROGRESSIVE, minimal. Yo M"iTcIrRosOcLoDpiGLcANADb,morSzKIaNl,ityTEEOTbHserved cosres TKeirlmliendalon sDaacyrif: ic2e3 Animal is signed oft from necropsy Gross pathology No MaLcIVrEoRs,copKiIcDNEAYbSm,orsTaHlYiRtOyIDOGbLsAeNrDv,edSKIN, TEETH istopathology 'IWNEFMMLTAOPTOILOESNI,S, SUEBXATCRUMTMEE/OCUHLRLOANRTYE,, siFnOiCAsLa,l minimal. eoTsNBTROPATIY, CHRONIC PROGRESSIVE, minimal. ~ No M"iHcRrYoRsOcLoDpiGLcANADb,norSmKIaNl,ityTEEOTbHserved DuPont 11574 --~ Company Sanitized. Doesnotcontain TSCACBI 18 | 2265-4D3a5y:StuRdeypeinatMeadl-eDoRsaetsDermal Tonicity --_ Individual Ansel Fachology Data Dose Group + VIE 1000 ma/kg sexs ales Animal Ret Wicroncopie & Macroscopic Findings Gosres | viTeoriemeiidntal$o8nseDSealry5inc:tia2co5eee teem mocropey axoss pathology Ho Macroscopic Abmorsality observed Hiseepathotony saver`:imoororests, ErTaEDLARY, Sinisa) Ho miScireovsceo,picTRAOtLmoSraGaLiAcDy,ObSsKer,veTdEETH asses TAKneiirTmneandlalo3n5saDacateyiimteic25oete from necropey ross patholosy inFiore, ThHROY GAR,SKIN, TEETH r-- ~~ mSNEENrAiTROOPPOATTEHSYI,S,CHERXOTNRIACMEPDRUOLGLRAERSYS,IVEm,inimmianli.sal 65766 Continued on the next page r+ DuPont11574 i | --~ | Company Sanitized. Donote contsain TSCA BY eeeee------------Tis0--- ---------- | H2:82-5D4a3y5S: RtepiuenaMdtaedly-eDoRsaetsDermal Toricity ~ Individual Anteal pathology pata Dose Grow : VIX 1000 mafka Sex: Males Jaina net Microscopic & Macroscopic Findings sesree Continued from previous page nistopacholosy Ho Mi"cTrRoRsOcToEpiGcLAADb,noSrKmIaNl,itTyERoTbHserved sasre7 nnKeiirlnalteandalo$n5sDSaiacgrynief:dic3oe5te from necropsy ross pathoteay : Ho Macroscopic Amomaiicy observed : Hatopachotony + `TwAhTzLoApSoAtTmIsOrNs,, SEUBTARCMUETENTCLHRAORNYI,C,siPnOiCsRLa,l.mininal. `RwCivRonTsuInOs,N,silAaC,UTEp,orsaidiodn,talperidontal - o Miocwroassco,piHcRAGbnToDrmGalLiaty, OSbKsIeNrved --~ asses RTFeiarlimlnieandalo3n5sBDaafcyirnietdi2co5ete trom necropsy ross pacholosy Wo Macroscopic Abnormality observed 665768 Continued on the nextpage.... DuPont11574 - - --~ Company Sanitized. Doesnotcontain TSCA CB! - 2285-4D3a5y;StuRdeypeinatMeadl-eDaRsaetsDermal Toxicity -- Individual Antoal pathology Data Dose Group: VIX 1000 ma/ky sex: Hales Sona Ret Wicroscopic acroscopic Findings Ges768 | Continued from previous page Hiscopachotony THDRAFTLOARROATTEISCIHS,,SUEBTARCNUETOEICLHLRAONRIYC,, mFiOnCiAsL], minimal. Ho Miocwroesc,opicTYARbnOoLrmGalLiAtDy,obSKsIeNr,vedTEETH assres tAKneiiirmTmaeilanao$8nsaDsciargyinfe+dic5e5oft from necropsy reas pathotony : Fo Miacvreors,copFiIcNEASm,ormTaHlYiRcOIyDOGbLsAeNrDv,edSK:IN, TEETH ---- sven`IwNoPrLoArBoArTeIsOtN,s,SUEBrArCvOeTnRO/CLHLRAORNIYC,, iFnOiCKeLl,.minieal. oesReCRRROOSPTAST,HYR,EPCKTHORCGRNLIUCULPARRO,GREPSOSOINV,E, Mimni(nRimaall ~ Wo M"icHrBosTcSopGiLcANADm,omSmKaIiNi,cyFaobEserved DuPont11574 | . | - Company Sanitized. Does not contaln TSCA CBI = 12285D4a3y5:StuRdeypienatMead-lDoRsesDermal Toricity -- Individund Animal Pathology Daca some Group VIZ 1000 sa/ks Sex: wales Sai wat Worossopl 4 masroseupis Fintings ses770 TlTeortemniaantasl50sBaSeciryniifai'c3oe9te exon necropsy prp-- o Macsoscopte Abmormatity Observed Hatopachalony ovatNRTeiENsAiTemOoPsOnTTuIEyOS,NI,S,cStUREROXANTCIROCATMSET/DRUOCLHGRLROAENRSIYSC,I.VRm,iPniOmmiCanli.manlf.oal so Microscopie Aomormaticy observes cam TE pormiic nand seaA cessscPep -- Gross sacholosy + Yo Maszoscopse Abmormalicy Gbaerved ~~ -- sa continued onmetsorcsercatsioss,s BXTIMEDULARY, siniesl. Dupont11574 |[ --~ Company Sanitized. Does not contain TSCACEY = -_-- 2512.5D4a3y5S;tdReypeinstMeld-eDoRstesDermalToiciy -- Sndividunt Anion Fashotosy Daca Dose Group + VII 1000 maf sexs nies Saini Wicroeoris 4 wasoscopls Findings Ga Continued teem previons page [rs---- A T------------ armors, CaRovEc sRGaRSSSIYE, mininal. Wo Microscopic mormatity chserved + DoPont11574 --_ --~ | | ------ Company Santized. Boos not contain TSCAcB EE --