Document e7k7JBOgLRJ0yJ3qmy2gkGz0p

AR A426 - 332] 503 AR226_ 332 Dupont13830 --~ TRADE SECRET Study Title H-25425:Repeated-DoseDermal Toxicity 28-Day Study in Male Rats TesT GUIDELINES: U.S. EPA Health Effects Test Guidelines OPPTS 870.3200 (1998) SOeEctCiDonG4u: idHeelailnteh fEofrfetchtesT,eNsutimnbgeofrC4h1e0mi(c19a8l1s) AuTHOR: Carol Finlay, BA. ~~ STUDY COMPLETED ON: November 3, 2004 PERFORMING LABORATORY: E.L du Pont de Nemours and Company HElakstkoenlRloTMaLda,bPo.rOa.toBroyxfo5r0Health and Environmental Sciences Newark, Delaware 19714-0050 LABORATORY PROJECTID: DuPont-13830 Wonk Request Novae (BY SERVICE CODE Nomen 0} SPONSOR: WEiLlLmdiungPtoonnt,dDeeNleawmaoruers1a9n89d8Company USA --_-- mm `CompanySanitized. DoesnotcontTSaCAiCnBI . H2-82D5a42y5:StuRdeypeinatMeadl-eDoRsaetsDermal Toxicity -- DuPont.13830 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 PrinciplesofGood Laboratory Practice (as revised 1997) published in ENV/MC/CHEM(98)17, except for the item documented below. Test substance characterization and stability analyses were performed at Regional Analytical Services (RAS), a non-GLP laboratory. The test substance analyses performed were in compliance with regulatory guidelines. Noneofthe aforementioned analyses were performed under Good Laboratory Practice Standards; however, the analyses were conducted in compliance with [S09002 regulations. Allof the analyses are considered valid and sufficient for the purposesofhis study. Appli/cSpaonnsotr: E.L du Pont de Nemours and Company Wilmington, Delaware 19898 USA. `StudyDirector: A aan Acs ae `Carol Filay, B.A. StaffToxicologist $3, Neu-2s04 Date Applicant/ Sponsor: DuPont Representative Date -- AA `Company Sanits ized. Does not contain TSCA Cal 1252.5D4a2y5:SRteypeiatnehdiDoRsaesDermal Toxicity ~ Duran 13830 QUALITY ASSURANCE DOCUMENTATION `Work Request Number: il Study Code Number: `dTahtescoofndiuncstpoecfttihoins asrteuidnydihcaastbeedebnelsouwb.jected to periodic Quality Assurance inspections. The Phase Audited Audit Dates Conduct: Evaluation 1 Dec 2003 Tables and Appendices 16, 18, 23 Feb 2004 `Tables and Appendices 23-26 Feb 2004 `Tablesand Appendices 9-12, 16Mar 2004 --- Report/Records: 6-8 Oct 2004 Dates Reported to Study Directorand Management 1 Dec 2003 23 Feb 2004 26 Feb 2004 16 Mar 2004 8 Oct 2004 Repost: _Aliza) 2 ;Qe Quality Ass`uM.raJnochensAtuodnitor 2p oof Date. Ps cs s me------------te-------- --r-- ---- a i Company Sanitized. Does not contain TSCA CBI a 142505 Repent Ds DelTosi po EER rereB-- ER CERTIFICATION `We, the undersigned, declare that this report provides an accurate evaluationofdata obtained from this study. Chiru atin br a7 nm DiplomateA.C.V.P. ) 0%~Mr Anicaln. Lof-tfo VeterinaryPathologist 0N033- elosser - =J ce o PEYEBnA YiN VeterinaryPathologist rer . er Suoam A Tnac Wir Sem Lelie `Senor Research Toxicologist 0022--4N0O0V.-22004 sa Tewfn oaeFtsobet reAir a tins `Staff Toxicologist 53. f4lou-Too ee eyn ro" 2285-0D2ay5:StuRdeypienatMeadl-eDRoastesDermal Toxicity -- Dupont13830 `TABLE OF CONTENTS Page GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT wcrc 2 QUALITY ASSURANCE DOCUMENTATION ccvcvsssssssmssssmsmssssssnnos3 CERTIFICATION cosmos LIST OF TABLES cvvosrsmssmssssssssssssssssssssssssssssmsssssssssssnon LIST OF FIGURES vss smn8 LIST OFAPPENDICES ccs STUDY INFORMATION ccna) EL |} INTRODUCTION cosmos 11 STUDYDESIGN crm 11 MATERIALS AND METHODS css 11 ~ B. TOE RURA Smmmmmrimmmmrgm-------------------------= 2 B. ATAGITADTIRY emmmmmmenmmmmsmmmonsinsmmmmmmmn 1 E. QuaraanndtPirenteset . on I- F. ASSIZ(A0Gmroeupnsantd SAY SHI cvs sssessssssnesrmsnnnon 13 G. TestSubstancePreparation and AAMIIStTAtion ..........mrrnmmmien 13 A m-- I. Food Consumption and Food EfCIENY.......rmnrmnrnrnn 1 1 CRSmmission 16 K. Total Fluorine and Perfluorooctancic Acid Level EVIUAUions..........ovrorrromen 14 L. Clinical PAhOIOgY EVAON...c.vosrsrssssrosesmsssssnesssssmnensmmsmnon 15 M.ANBIOMic PAhOIORY EVAIUAON..crovenrmrersmrrenrmsrsmsonemsensmnnrnssnenemn 17 RSs ARUN mgm 1 RESULTS AND DISCUSSION c.ccvonssmsmmonmsmsmssmssssmssssmssssmsssssssmssmssnen 19 J ----. J A. Mean Body Weights and Body Weight GainS............creeesmmsreveis 19 B. Food Consumption and F00d EfTCIENCY.........wvemrreemnenrrensnonenrins 19 C. Clinical Observations, Dermal Effects, and MOMEIY .......ouevrvenres 19 D. Perfluorooctanoic Acid (PFOA) and Total Fluorine Evaluations......... wr B) Tabi COR) J ---------------- | ~ I A -- `CompanySanitized.Doesnot conTtSaCAiCn8 H-25425: RepeateDedrm-alDTooxiscitey 28-Day Study in Male Rats DuPont-13830 ~ B. COMPO puss wd] C.. ClniCal CHEMISTY: 21 D. UHDBIYSES corns 21 E. Urine and PLASMA FIORE... 22. F. Clinical Pathology CONCIISIONS .......svvsnrsissnis 22. Anatomic Pathology EVAIIAtON wom32 A CIS ADIG crssmimsenmsn32 B. OBA WEIGHS... 22 C.. GIOSS OBSCIVAONS vcore 32 : MOBO FRING psupmmmmsmmmmmmmmmm--il E. Anatomic Pathology CONCIUSIONS .......sssrssimmnnsis23 CONCLUSIONS oss 34 RECORDS AND SAMPLE STORAGE worms 24 REFERENCES sss 35 TABLES cms26 TC ----_ APPENDICES oss 54. re Company Sanitized. DoesnotcontTSaCAiCBnI 1.25425: Repeated-Dose Dermal Toxicity 28-Day Study in Male Rats -- DuPont 13830 LIST OF TABLES Page 1. MEAN BODY WEIGHTS OFMALERATS... mmm------" 2. MEANBODYWEIGGAIHNSTOFMALERATS......... semmmmgm----y 3. MEANDAILY FOODCONSUMBYPMATLEION RATS.. wnt 4. MEANDAILYFOODEFFICOIFMEALNECRAYTS. SR 5. SUMMARY OFCLINICALOBSERVATIONSFORMALERATS -PREDOSING. vcr 33 6. SUMMARY OFCLINICALOBSERVATIONSFORMALERATS -POSTDOSING v.35 7. PERCENTSURVIVALOFMALE RATS... prmmmmnniS7 8. MEAN PFOACONCENTRAINTMAILEORANTSS... smith 9. MEASUREDCONCENTRATION(PPB)WHOLE BLOODFLUORINE ...c.c.ccrsreessncrns39 10. SUOM FHEM MATOA LOGR YVALY UES FORMALERATS... 11. SUOM FCOM AGULA ATIOR NVALY UES FORMALERATS... smd 12.SUMMARYOFCLINICALCHEMISTRY VALUES FORMALE RATS... A 13. SUMOMFURAINARLYSYIS VAFLORU MALE E RASTS... wsdl --_ 14. MEANFINAL BODYAND ORGAN WEIFOGRMHALETS RATS... -- 15. INCIDENCES OF GROSS OBSERVAINTMAILEORNATSS. FAAS a 16. INCIDENCESAND LESION GRADES OF MICROSCOPIC OBSERVAINTMIALOERNATSS. a --~ --_--_-- Company Sanitized. Doesnot contain TSCA C81 12.82D54a2y5:StuRdeypeinatMeadl-eDoRsaetDsermal Toxicity LI OFFS IGUT RES 1. MEANBODY WEIOFGMAHLETS RATS.. Dupont 13830 Page mmm LIST OF APPENDICES Page A. INDIVBOIDYDWEUIGAHTLS... wasmmm----_ B. INDIFOVODICONDSUUMPATIOLN... wmmmm---- C. INDIVIDUALCLINICAL OBSERVATIONSAND MORTALITY RECORDS... 10 D. INDIVIDUALCLINICAL OBSERVA- TIONS POSTDING. smmm-- E._ INDEDIEMAVANDIERYDTHEU MASA COREL S... I F. PFOA ANALYTICALREPORT c.csmssssssmssmsssssnsis e119 G. INDIBLOVODIFLUDORIUNELAEVELLS... wml --_ H. INDIVIDUALANIMAL CLINICAL PATHOLOGY DATA vc -- I. INDIVIDUAL ANIMAL BODYAND ORGAN WEIGHTS... 209 J. INDIVIDUALANIMAL GROSS AND MICROSCOPICOBSERVATIONS... 23 --_ eee Company Sanitized. Does notcontainTSCA CBI 1A2585,bReeeeDotDerm Tory ~ STUDY INFORMATION oth Colective on -- || Smonms/Coes: -(NE| HaskellNumber: 25425 CAS Registry Number: [SN i ) --} `Study Initiated/Completed: November 18, 2003/(see report cover page) In-life Initiated/Completed: November 25, 2003 / December 23, 2003 = `Company Sanitized. Does not contain TSCA CBI 12.82-5D4a2y5:StuRdeypeinatMeadl-eDoRsaetsDermal Tosicity PN SUMMARY DuPont 13830 `The objectiveofthis study was to determine the potential toxicity ofH-25425 following repeated dermal exposure. The test substance was applied to the shaved, intact skinof male Crl:CD(SD)IGS BR rats for 6 hours/day for 28 consecutive days. Three groups of 10 male rats were treated dermally with 10, 100, or 1000 mg/kg/day H-25425. 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 0,7, 14,21, and 27. Theday 21 samples were analyzed. Bloodand urinesampleswere: collected for clinical pathology prior to sacrifice on day 28. Blood samples were collected at necropsy for analysisofconcentrationofperfluorooctanoic acid (PFOA). All rats underwent necropsy for gross and microscopic pathological evaluation. No deaths occurred, and no test substance-related effects on body weight or nutritional parameters were observed. No clinical signs attributable to systemic toxicity occurred. No dermal irritation was observed during the study. PFOA concentrations in plasma from rats in the control group and the 10 mg/kg/day group were. below the lower limitof quantitati(o10n ppb). The mean concentrations were 13 ppb in the --~ 100 mg/kg/day group and 105 ppb in the 1000 mg/kg/day group. Fluorine levels in blood from treated and control rats were either not detectable or below the limit of quantification (500 ppb). No adverse effects were observed on any clinical pathology parameters (hematology, clinical chemistry, coagulation parameters, urinalysis), organ weights, or gross or microscopic pathology parameters. `The no-observed-effect level (NOEL)' for male rats was 1000 mg/kg/day, the highest dosage tested. The NOEL is based on a lack ofadverse test substance-related effects on any in-life, clinical pathology, or anatomic pathology parameter in male rats treated dermally at dosages up to 1000 mg/kg/day. + Tefhfeecntso-aotbrsiebrvueadb-leeffteoctte(NeOtELsu)bsftrantchieswsetruedynios ddeefteicnteedd.asTthhuesh,igfhoersttidsossteudaty,whthiecNhOtoExLicoiloegqiuciavlalleinmtp(o0rttahnet --_ 'efNfOecEtLeavsedle(fiNnOeAdEbLy)thaesUdneiftienddSbtyaetsheEnEvuirroopnemaenntUarlioPnro(t1e9c9t4i)o.n Agency (1985), and th no-observed-adverse- EE `Company Saniized. Does not contain TSCA CBI H2-82-5D4a2y5S:tuRdeypeinatMeadl-eDoRsatesDermal Toricity DuPont13830 INTRODUCTION The test substance, H-25425, is belongs to the groupofcompounds known It a previously conducted 90-day oral gavage study with the test substance, maleand female rats were dosed at 0 (control), 10, w1e0i0g,hotr, 1b0o0d0y mwge/igkhgtfgoarin9,0 fcooondseccountsiuvmepdtaiyons,.'foNood eafdfviecriesnecyte,storsucblsintiacnaclep-artehloalteodgeyfpfeacrtasmoetnerbsody hwyepreertorbospehryvewdaisnoabnsyermvaeldeionrtfheem1a0le00domsge/kggr/oudpa.y mRaelveerasinbdlef,emmailneimgraoluptso.miTlhdethnyor-ooibdsefrolvleidc-ular effect level (NOEL) for subchronic toxicity endpoints in male and female rats was 100 mg/kg/day. Dose study. levels for the present study were selected to duplicate the dose levelsofthe oral gavage STUDY DESIGN Group Number/Group Dosage (mg/kg) xX 10 0 (Control) --_ XI 10 10 xm 10 100 Xv 10 1000 MATERIALS AND METHODS A. Test Guidelines The study design complies with the following test guidelines except as noted below: + POrfoftiecceotifonPrAegveenntciyon(,EPPeAs)ti(c1i9d9e8s).anOdPTPoxTiSc 8S7u0bs.t3a2n0c0e2s1(/O2P8P-DTaSy)DUe.Sr.maElnvToixriocnimtye.ntaHlealth Effects Test Guidelines. + ODrogsaeniDseartmiaonlfToorxiEcciotyn:om2i1c/2C8o--ODpaeyrSattuidoy.n aGnudiDdeelvienleofpomretnhte(TOesEtCiDng)of(19C8h1e)m.ica4l1s0.Repeated tEhxecseeptoiccoans-ioTnhsethweryapmpaiyngnsoot hf7avreatbsebeenceaxmpeodsiesdlotodgtehde dteusrtinsgubtshteaencxepfoosrur6ehpoeurriso.d.FoThuerroefftohree,seon araftfsecwtetrhee ionbjtehcetciovnetsroorltghreouvpa,liadintdyotfhrteheerasttsuwdyerbeecianudsief,fecroennstitdeesrtignrgouthpast. noThsiisgneixfciecpanttion did not toxicological effects were observed at any dosage level, i is not likely that an occasional ~ exposure periodof less than 6 hours for some animals would have changed the study results. - `Company Sanitized. Doesnotcontain TSCA CBI H2-82-5D4a2y5S:udReypeinatMeadl-eDoRsactsDermal Toxicity ~~ `Emxacleepstwieorne-mOonrleysmeanlseitriavtestwoetrheettroexaitceodlobgeiccaaulseeffiencptrsetvhiaonusfesmtauldeise.s with. Dupont 13830 1 B. Test Substance `teTshtestuesbtstsaunbcsetaanpcpee,aHr-e2d5t4o2b5e, swtaasblseuupnpdleiretdhbeyctohnedsiptioonnssoorftashe=-- Study. No evidence of instability, suchas a change in color or physical state, was observed. C. TestSpecies OOcntoNboevre6m,b2e0r031,8,we20r0e3r,e4ce4imveadlefrCorml:CChaDr*l(eSsDR)iIvGeSrBLaRborraatts,orwiietsh, aInnc.a,ssRiaglneeigdhb,irNtohrdtahteCaorfolina. `The Crl:CD(SD)IGS BR extensive experience with rat the wsatrsaisnelaetcHtaesdkbealsleLdaboonractoonrsiys.tently acceptable health status and on D. Animal Husbandry 1. Housing ~~ Rats were housed siinnsgtailnleyss steel, wire-mesh cages suspended above cage boards. 2. Environmental Conditions Animal Animal rooms rooms were were maintained at a temperature of 18-26C and artificially illuminated (fluorescent light) on a relative humidityof 30-70%. an approximate 12-hour light/dark cycle. 3. Feed and Water `Tap water was provided ad libitum. PMI Nutrition International, LLC Certified Rodent LabDiet 5002 meal was available ad libitum except when the rats were fasted. 4. Mdentification Poruitosridteooafsstisgcnamgeen.tAtfoigerroauspssi,genamcehnrtattowagsroutpesm,poeraacrhilryatiwdeanstiafsisedigbnyedacaangaenciamradl affixed number to the which was tattooed on the tal ofeach rat and included on the cage labels. 5. Animal Health and Environmental Monitoring Program AfosllspoewciinfgipedroicnetdhuereHsasakreelpleLrafboorrmaetdorpyerainoidimcaalllhyeatlotehnasnudreetnhvaitrconomnetnatmailnamnotniltevoerlisngarperboeglroamw, the --_ those that would be expected to impact the scientific integrityofthe study: ee `Company Sanie tzed.e Does i not cot ntain-- TSCA--CBI H2.82-5D4a2y5:StuRdyeinpMelaetRaetDsder-maDleToxoicsitey Dupont13830 --~ + 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 requirements and not to exceed stated maximum concentrations of key contaminants, including specified heavy metals, aflatoxin, chlorinated hydrocarbons, and organophosphates. The 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 the attending laboratory animal veterinarian. Evaluationofthese data did not indicate any conditions that affected the validityofthe study. E. Quarantine and Pretest Upon arrival at Haskell Laboratory, the rats were removed from shipping cartons and quarantined for 6 days. "The rats were weighed 3 times during the quarantine period and examined daily for -- any clinically apparent signsof disease or injury. The rats were observed daily for mortalityand signs of illness, injury, or abnormal behavior. On the basesofacceptable body weight gains and freedom from clinically apparent signs of disease or injury, the ras were released from quarantine on testday-1 by the laboratory animal veterinarian. F. Assignmentto Groups and Study Start Forty rats were selected for study use on the basesofadequate body weight gain, freedom from clinical signsofdisease or injury, and a body weight within + 20%ofthe mean. The selected rats were divided by computerized, stratified randomization into 4 groups of 10rats, so that there `were no statistically significant differences among group body weight means. Dose administration with H-25425 began on test day 0 when the rats were approximately 7 weeks ofage. G. Test Substance Preparation and Administration Approximately 24 hours prior to the first treatment, the furofeach rat was closely shaved to expose the skin from the back and trunk. The area to be treated was marked on the backof each rat with a water-insoluble marker. The rats were treated for 28 consecutive days at ~ `approximately the same time each day. The exposure period was approximately 6 hours per day. -_-- Company Sanitized. Doesnot containTSCA CBI H2-82D5a42y5S:tuRdeypeinstMeadl-eDoRsactsDermal Toxicity DuPont13830 ~ `The test substance was moistened with deionized water to form a thick paste and applied as evenly and thinly as possible to the test site. The amountoftest substance needed to treat cach rat was based on the most recently determined body weight measurement. The control rats were treated with deionized water. The test site was covered with a 2-ply porous gauze dressing followed by successive layersofstretch gauze (no more than layers) and self-adhesive bandage. After the exposure period, the wrappings were removed and excess test substance was washed offwith warm tap water. Each rat was then gently patted dry and retumed to the cage. The control animals received the same washing technique as the treated animals. Tt was not possible to cover an area of 10%ofthe total body surface for any dose group without excessively diluting the test substance. The approximate total body surface area covered with the thick paste for the 10, 100, and 1000 mg/kg/day groups was 1%, 1%, and 3.3%, respectively. Following an evaluation rats were reshaved as needed during the study. The entire area that was originally shaved (including the untreated control skin) was reshaved. H. Body Weights The rats were weighed at 3-4 day intervals throughout the study. IL 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 each feeder at the beginning and endofthe 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. Observations `The rats were observed for clinical signs and dermal effects after washing. The rats were also observed for clinical signs at each weighing. The Draize Scale was used to score skin imitation. Adjacentareasofuntreated skin were used for comparison. The rats were checked twice daily for mortality and for signsofillness, injury, or abnormal behavior. K. Total Fluorine and Perfluorooctanoic Acid Level Evaluations Blood was collected into EDTA tubes from the orbital sinusofal rats on test days 0, 7, 14, 21, and 27 approximately one hour after removalofthe test substance. The blood was refrigerated. `The total fluorine content ofthe day 21 blood samples was determined by using a Wickbold torch ~ combustion method followed by analysis with a fluoride ion selective electrode.?) The limit of - a -- `Company Sanitized. Doesnotcontain TSCA CBI H2.82-5D4a2y5:StuRdeypeinatMeadl-eDoRsaetsDermal Toxicity Dupont 13830 ~ quantification (LOQ) for this method is 500 ppb. Fluorine blood analysis was performed at Stereochem, Newark, Delaware. `Additional blood was collected from the vena cavaofall rats at necropsy into a tube containing EDTA. Plasma was prepared and stored frozen at 80C to -20C until analyzed for concentrationof perfluorooctanoic acid (PFOA). PFOA was extracted fromtheplasma by protein precipitation in acetonitrile. The compound was quantified by liquid chromatography/tandem mass spectrometry (LC/MS/MS) analysis using selected reaction `monitoring (SRM). Quantification was performed using extracted calibration standards containing an internal standard. The lower limitof quantitation (LLOQ) for this method is 10 ppb. Plasma samples were analyzed for PFOA at Exygen Research, 3058 Research Drive, State College, PA 16801. See Appendix F for additional details ofthis analysis. L. Clinical Pathology Evaluation A clinical pathology evaluation was conducted on all animals 28 days aftr initiationofthe study. `The day before collection of samples for the clinical pathology evaluation animals were placed in `metabolism cages. Animals were fasted overnight (approximately 16 hours) and urine collected from each animal. Blood samples for hematology and clinical chemistry measurements were collected fromtheorbital sinusofeach animal while the animal was under carbon dioxide `anesthesia. Blood samples for plasma fluoride, PFOA, and coagulation parameters were collected at sacrifice from the abdominal vena cavaofeach animal while the animal was under ~~ carbon dioxide anesthesia. Additional blood collected from the vena cava was placed in a serum tube, processed toserum,and frozen at -80C. Serum was discarded without analysis because further tests were not required (0 support experimental findings. Bone marrow smears were. inadvertently not collected at sacrifice. All blood samples were evaluated for quality by visual `examination prior to analysis. Results were maintained in the study records and reported only if the sample was analyzed. 1. Hematology and Coagulation Cheommaptloeltoegbylaonoadlcyozuenrtosr, dientcelrumdiinngedreftricoumlomciyctreso,scwoepriec deevtaelruamtiinoendofonthaeBbalyoeordsAmdevair.a 120 Wright- Giemsa stained blood smears from all animals were examined microscopically for confirmation of automated results and evaluationof cellular morphology. Blood smears, stained with new methylene blue, were prepared from each animal undergoing a hematology evaluation, but were nCootagnueleadteidonfoArnaelxyazmeirn.ation. Coagulation times were determined on a Sysmex CA-1000 `The following parameters were determined: red blood cell count hemoglobin hematocrit ~~ mean corpuscular volume platelet count `white blood cell count differential white blood cell count microscopic blood smear examination -_-- CompanySanitized. Does notcontTSaCAiCnBI H2.82-5D4a2y5:StuRdeypeinatMeadl-eDoRsaetsDermal Toricity ~ `mean corpuscular hemoglobin `mean corpuscular hemoglobin concentration red cell distribution width absolute reticulocyte count DuPont 13830 pacrtoitvhartoemdbpianrttiailmethromboplastin time 2. Clinical Chemistry `Serum clinical chemistry parameters were determined on an Hitachi 717 clinical chemistry. PanHa/lIyzSeEr.mePtlerasamnad falufolruiodreidceo-nsceelnetcrtaivteioenlsecwtreordee.determined using a Beckman 12 digital The following parameters were determined: aspartate aminotransferase: alanine aminotransferase sorbitol dehydrogenase alkaline phosphatase: total bilirubin urea nitrogen --_ creatinine cholesterol triglycerides glucose total protein albumin globulin calcium inorganic phosphorus. sodium potassium chloride Mioride 3. Urinalysis Urine volume and appearance (quality, color, and clarity) were measured and evaluated visually, Areustpoecmtaitveeldy.UrUirnienCehceomnissttitruyeanntaslwyzeerre. seUmrii-nqeuapnrtoitteaitniwvealsymmeeaassuurreedd oonn aanBHaiytearchCili7n1i7tecklinAitcallasTM chemistry analyzer. Urine osmolality was determined using an Advanced Osmometer 3900. Urine fluoride concentrations were determined using a Beckman 12 digital pH/ISE meter and a fluoride-selective electrode, and total urine fluorides were calculated (volume x concentration). Sediments from all urine specimens were evaluated microscopically. `The following parameters were determined: cquoalloirty clarity volume osmolality bkieltiornuebin blood urobilinogen fluoride ft + Fluoride determination was analyzed on EDTA plasma, - `CompanySaniized. Doesnot contTSaCAiCnBI H2.62:5D4a2y5:StuRdeypeinatMeadl-eDoRsaetsDermal Toxicity Dupont 13830 --~ pH glucose protein `microscopic urine sediment examination M. Anatomic Pathology Evaluation After 28 days ofexposure to the test substance (test day 28), groups of 10 male rats from the 0, 10, 100, and 1000 mg/kg/daygroupswere sacrificedandnecropsied. "The rats were fasted overnight on the afternoon before their scheduled sacrifice. The order of sacrifice for scheduled deaths was random among all treatment groups. Rats were euthanized by carbon dioxide anesthesia and exsanguination. Gross examinations were performed on all rats. The following tissues were collected from all rats. Tver kidneys sskkiinn ((turnetarteeadt)ed) thyroid gland gross observation4s a. Garnosdsmaibsssienrgvtainoantsommiacdpearats)newcerroepgseynefroallwyhincohthciosltlocptaetdh.ology was not appropriate (c uid, ruffed for, `The following tissues were weighed: liver, kidneys,and thyroid gland (afer fixation). Organ --~ `weight/final body weight ratios were calculated. Gross lesions for which a microscopic diagnosis would not be additive (c.g., osteoarthritis, `pododermatitis, chronic dermatitis ofthe tai, urinary calculi, and deformity ofthe teeth, toe, tail or pinna) were saved but were generally not processed for microscopic evaluation. All tissues were fixed in 10% neutral buffered formalin. Processed tissues were embedded in `paraffin, cut ata nominal thickness of micrometers, tained with hematoxylin and cosin (H&E), and examined microscopically. All collected tissues from rats in the control and 1000 mg/kg/day groups were processed to slides and receiveda full histopathological examination. N. Statistical Analyses Significance wasjudged at p <0.05. ry fra Te PaBSroaedmyeWWteeiarghtce Preliminary Test sSiegqnuiefnitciaanlteapnpliacavtioan mo|f|esilgnipiificnanyt ve r Food Consumption rend es peinvis comparison --_ Food Efficiency ee] -_-- `Company Sanitized. Does not contain TSCA CBI 2152.5D4a2y5S:tRdeypeiantMeadlDeoRsaesDel Tosiity Duron 13530 ~ Eprlminary ets ot |Epler 0 Organ Weight [rp -- Sarval IncidOelnsceerovfatColninsi:cal Ty Shap Wilk test? for Loveenl's for pita 0 |Ovenof |KalWala et" | variance" followed with | followed with Dunn's Dunnett's testTM > test | vDOanurein-nwecaesyaenfaollylssoiwseodfwits || Kelrsufslkael-Wwailtlhisut'esst" Cochran-Armitage test for trend IsPeaniirwtSicshenatcionmprWiiskoncssntdwasssootsastiegndifpicraentlbiotmLiesvesnswecrset wnlsycsoingdnuicftiedcafhroebutst vorecrk oosffDniueeodtnwsasst Waohsnesneada.nlditevshioedrudSaheladpGviharlsoucer.WvialFtkoornsavtmawsparlseecionridfealdnit,breKivunesgasephWralacldics2ce.s0tr.v1a,vs0fl.o0,l5locwwauesldaubtsyidDofnousaswneyerctlp.eursfoiromneds performed i htbib on d BIfotnhieeirnocniidecnocneecwtaisonnowtassigunsifdi.cant, but a significant lackoffit occurred, then Fisher's Exact test' with a --- -- --_-- Company Sanizsd. Does notcontain TSCA Ca1 H2-82-5D4a2y5S:tuRdy ien MpaleDeoRsaetaDsertmaelTodric:ity --~ RESULTS AND DISCUSSION Dupont 13830 Tu-Life Toxicology A. Mean Body Weights and Body Weight Gains (Tables 1-2, Figure 1, Appendix A) No test substance-related effects on mean body weights or mean body weight gains were observed in any groupofmale rats. No statistically significant differences in mean body weights were observed. Mean body weight gains in all groups were greater than control over some intervals (not statistically significant). Mean body weight gains in all test groups were statistically decreased compared to control in the interval days 10-14. The differences were not considered test substance-related because they did not exhibit a monotonic dose-response. The nmoetacnonosveirdaelrledbotdoybewetiegsthtsugbasitnasncien-arlellatetsetdgbreocuapussewetrheeylwoewerre tnhoatnstcaotnitsrtoilc.allTyhseigdniifffiecraenntcaensdwedride not exhibit a monotonic dose-response. --_ B. Food Consumption and Food Efficiency (Tables 3-4, Appendix B) No effects on food consumption were observed. Mean overall food consumption (test days 0-27) in the 1000 mg/kg/day group was 101%ofcontrol (not statistically significant). No test substance-relatedeffectson food efficiency were observed. Mean food efficiency was statistically decreased in the interval days 7-14 at al dosages. These differences were not considered test substance-related because they did not exhibit a monotonic dose response. Mean overall food efficiency was statistically decreased in the 100 and 1000 mg/kg/day groups. These differences were not considered test substance-related because they were 10% or less than control, mean food efficiency in these groups was greater than control over 1 or 2 weekly intervals (not statistically significant), and the decreased food efficiency did not result in any reduction in final body weight or overall body weight gain. C. Clinical Observations, Dermal Effects, and Mortality (Tables 5-7, Appendices C-E) wNeoreclninoitcaclonssiigdnesrreedsutletsitnsgufbsrtoamncsey-srteelmaitcedtoaxsitchietyywocecruerroebds.erOvceudlairn dbiostchhatrregaeteadndanndascaolntdrioslcharge animals. Dark eyes, comeal opacity, or enophthalmus were observed in several rats during the --_ nstoutdye.xhiTbhietsaemcolnionitcoanl iscigdnossweerreespnoontsec.onsTihdeesreedsitgesnts smuabsytabnecear-erseullatteodfborebciatuasle stihneusinbcliededeinncge, did - Company Sanitized. Doesnotcontain TSCA CBI H282-5D4a2y5:StuRdeypeinatMeadl-eDoRsaetsDermal Toricity Dupont13830 ~ Hair loss, superficial wounds, swollen face, and stainingofthe fur/skin were present in both treated and control animals and were not considered test substance-related. No dermal irritation was observed during the study. No deaths occurred. D. Perfluorooctanic Acid (PFOA) and Total Fluorine Evaluations (Tables 8-9, Appendices F-G) PFOA concentrations in plasma from rats in the control group and the 10 mg/kg/day group were below the lower limitofquantitation (LLOQ or 10 ppb). The mean concentrations were 13 ppb in the 100 mg/kg/day group and 105 ppb in the 1000 mg/kg/day group. These levels were cthoensPiFdeOrAabliyn tlhoeweprlatshmaan,twhhoestehoebrsefrrvoemddiinretchteaoprpallicsattuidoynwoirtmhetthaisbotelsitssmuobfstcahnecmei.c"alTihnetsheoutrecste of substance, is unknown. Fluorine levels in blood from treated and control rats were either not detectableorbelow the limitof quantification (LOQ or 500 ppb). This is in contrast with the measurable total fluorine evident in animals dosed at al levels (10 mg/kg/day and above) in the oral study. --~ E. In-Life Conclusions No adverse effects were observed on mean body weight, nutritional parameters, mortality, or clinical signs in male rats treated up to and including 1000 mg/kg/day. PFOA was present in plasma from rats treated at 100 and 1000 mg/kg/day. Blood fluorine levels were not detectable at levels above the LOQof 500 ppb inanydose group. Clinical Pathology Evaluation A. Hematology (Table 10, Appendix H) `There were no adverse changes in hematologic parameters in male rats. The following statistically significant changes in mean hematologic parameters were not related to treatment: + Mean corpuscular hemoglobin concentration was minimally but statistically increased in `omcacluersitnreaatdeodsew-irtehla1t0edorpa1tt0e0r0n,magn/dkgwe(rbeotthhe1r0ef2o%roefcocnosnitdreorlemdetaon)b.e uTnhreeslaetecdhatnogterseadtimdennto.t --~ -_-- Company Sanitized. Does not contain TSCA CBI 2H-82-5D4a2y5;StuRdeypeinstMcadl-eDoRsaetsDermalToricity DuPont.13830 ~ B. Coagulation (Table 11, Appendix H) `mTahleererawtse.re no treatment-related or statistically significant changes in coagulation parameters in C. Clinical Chemistry (Table 12, Appendix H) `There were no adverse changes in clinical chemistry parameters in male rats. The following statistically significant changes in mean clinical chemistry parameters were cither treatmentrelated and not adverse, or not related to exposure to compound: + Minimally decreased urea nitrogen and creatinine in males treated with 100 or 1000mg/kg were considered 10 be treatment-related. Mean concentrationsofurea nitrogen were 83% of controls in both groups, while mean creatinine concentrations were 83% and 76%ofcontrols inratstreated with 100 or 1000 mg/kg, respectively. In addition, with the exception of one: rat treated with 10 mg/kg, creatinine concentrationsofthis group were also decreased. Generally, increases in urea nitrogen and creatinine are considered adverse; minimal decreases in these parameters have no toxicologic significance. The causeofminimally decreased urea nitrogen and creatinine was not addressed in this study. --~ + C1h0o0l0esmtge/roklga(nstdattirsitgilcyaclelyrisdiegnciofnicceannttroantliyonfsorwecrhoelemsitneirmola;llmyedaencsrewaesreedi8n1m%alaends 7tr2ea%teodfwith respective controls). These decreases were likely to be treatment.related based on the distributionofthe individual animal dataincomparison to control rats. However, because the rangeof individual values was similar between control and 1000 mg/kg groups, these: changes were considered to be non-adverse. + Potassium was minimally decreased (statistically significant) in males treated with 1000 mg/kg (90%of control group mean). This decrease was likely to be treatment-related based on the consistencyofthe individual animal data. However, in comparison to historical Iaboratory data, individual animal potassium concentrations in both the control and 100 mg/kg groupsofrats were within the historical range for individual animal values (5.17.3 mmol/L), with the exception ofone outlier in the control group (#902) with a phiosttaosrisciaulmrcaonngceeonftrmaetaionnsof(57..77-62.5mmmomlo/lL/.L)I.naTdhdeirteifoonr,e,methainsschfaonrgbeo,thalgtrhoouupgshwterreaetmweintth-in the related, was not considered to be adverse. D. Urinalyses (Table 13, Appendix H) `There were no adverse changes in urinalysis parameters in male rats. The following statistically significant change was not related to treatment -- t TT ee `Company Sanitzed.Doen snotcontain TSCA CBI H2-82-5D4a2y5;StuRdeypeinatMeadl-eDoRsaeisDermal Toxicity Dupont13830 ~~ + Urine protein was increased in males treated with 10 mg/kg. This change occurred only in the low dose group, and therefore was considered to be unrelated to compound. E. Urine and Plasma Fluoride (Tables 12-13, Appendix H) `There were no statistically significant or treatment-related changes in plasma fluoride or urine fluoride at the endofthe dosing period. F. Clinical Pathology Conclusions Treating male rats dermally with H-25425 at dosages up to 1000 mg/kg for 28 days resulted in `minimally decreased urea nitrogen and creatinine at 100 and 1000 mg/kg/day and minimally decreased cholesteral, triglycerides, and potassium at 1000 mg/kg/day. Noneofthese changes wereconsidered to be adverse. Therefore, there were no adverse effects on hematology, coagulation, clinical chemistry, or urinalysis parameters in the dermal study which is consistent with the oral study. Anatomic Pathology Evaluation --~ A. Causeof Death (Appendix J) `There were no test substance-related deaths. All 40 rats survived until the scheduled 28-day sacrifice. B. Organ Weights (Table 14, Appendix I) `There were no dermal exposure-related effects on absolute or relative organ weights. All individual and mean organ weight differences were considered (0 be spurious and unrelated to test substance administration. C. Gross Observations (Table 15, Appendix J) `There were no test substance-related gross observations. The three gross observations made at necropsy were interpreted to be incidental lesions unrelated to test substance administration. --_ -_-- `CompanySanitized.Doesnot conTtSaCAiCBnI H2:82-5D4a2y5S:tuRdeypeinatMeadl-eDoRsaetsDermal Tosiciy DuPont13830 ~ D. Microscopic Findings (Table 16, Appendix J) `There were no test substance-related microscopic findings. All microscopic findingsinthis studyareknown tooccurnaturally in ratsofthis stock and age and were not present in a doseresponse fashion in either incidence or severity. E. Anatomic Pathology Conclusions No adverse effects were observed on mortality, organ weights, gross pathology, or histopathology in male rats treated dermally up to and including 1000 mg/kg/day. This is in contrast with the reversible, minimal to mild thyroid follicular hypertrophy observed at 1000 mg/kg/day in the oral study. --~ --_ EE `Company Sanitized. DE oesnotcE ontain TSCA CBI H2-82-5D4a2y5S;tuRdy ien VpaleDeoRsaetaDsertmaelTodxic:ity PN DuPont 13830 CONCLUSIONS Urantdsewrasthe10c0o0ndmigt/ikongs/odfayt,hitshesthuidgyh,estthedonos-aogbesetersvteedd.-efTfhecetNlOevEelL(iNsObEaLs)e'd ofonraH-la2c5ko42f5adinvemrasleetest `smuablsetarnactes-trreelaatteedddeefrfmeacltslyonatadnoysaing-elsifue,pctloini1c0a0l0pamtgh/oklgo/gdya,y.or anatomic pathology parameter in RECORDS AND SAMPLE STORAGE All data and records for analytical characterizations conducted by or for the sponsor will be retained by the sponsor. equipment records will Laboratory-specific or site-specific be retained by the facility where the raw data, work was such as done. personnel files and A sampleofthe test substance will be collected for archive purposes and retained at Haskell Laboratory, Newark, Delaware. Specimens (ifapplicable), raw data, and the final report will be retained at Haskell Laboratory, Newark, Delaware or at Iron Mountain Records Management, `Wilmington, Delaware. ~ * TthheeteNstOEsuLbfsotratnhcieswesrteudnyoitsddeetfeictneedd.asTthhse,hifgohretstisdossteudayt,wthheicNhOtEoiLcoisloegquiicvaallyenitmp0ortthaenNt OefEfeLctsastdieifbiuntedabblyto the United States Environmental Protection Ageney and o the no-observed-advers-effct level (NOAEL) as definedbythe European Union 09 -=Company Sanitized. Does not contain TSCA CBI H2-82.5D4a2y5;StuRdeypeinaetMelde-eDoRsaetsDermal Toxicity --~ DDuwPoonmt.i1m38m30 REFERENCES 1. DRautPsownittHhaOsnkee-llGeLnaebroartaitoonryRe(2p0r0o3d)u.ctHi-o2n5E4v2a5l:uatSiuobncsh.roUnnipcubTloxiischietdy,e9r0-oDa,y Gavage Study in 2. CblaopokdaaVt.t,rBacoewecrosnc,eCn.r,aNtairovnelseevne,lsJ.bNy.,thaendWiRcokssbio,lRd.dFe.coDmeptoesrimtiinoantimoenothfotdotwailtfhludoirreicnte in potentiometric detection. Talanta 2004 accepted for publication. 3. DWrialpeeyr,,NNeRw.Yaornkd.Smith, H. (1981). Applied Regression Analysis, 2TM edition, pp 266.273. 4. Saneilmwayln,saMfRet.y s(t1u9d9ie5s)..TJhouerunsaelofoftthreenAdmetersitcsatno dCeotlelremgienoefTaonxo-iocbosleorgvyab1l4e(-2c)f,fe15c8t-l1e6v8e.l in 5. Jonckheere, AR. (1954). Biometrika 41, 133-145. Adistribution-free K-sample test against ordered alternatives. 6. SLteavteisntei,csH.(1.(1O9l6k0i)n., eRdo.b)upspt 2te7s8t-f2o9r2c.quSatlaintfyoorfdvUanriivaenrcseis.tyCPornestsr,ibPuatlioonAslttoo.Probability and 7. Shapiro, $5. and Wilk., M.B. (1965). samples). Biometrika 52, 591-611. An analysisofvariance test for normality (complete ~ 8. Snedecor, 349-352. G.W. and The lowa Cochran, W.G. State University (1967). Press, Statistical Iowa. Methods, 6" edition, pp 246-248 and 9. Dunnett, CW. (1964). 482-491. New tables for multiple comparisons with a control. Biometrics 20, 10. Dunnett, C.W. (1980). Pairwise Statist. Assoc. 75, 796-800. multiple comparisons in the unequal variance case. J. Amer. 11. Tunaemqhuaanlev,arAi.aCn.ce(s1.97J9.)A.meAr.coSmtpatairsti.soAnsosofc.pr7o4c,e4d7u1r-e4s8f0o.r multiple comparisonof means with 12. Kruskal, J. Amer. WH. and Wallis, Statist. Assoc. 47, W.A. (1952). 583-621. Useofranks in one-criterion analysisofvariance 13. Dunn, 0.1. (1964). Multiple contrasts using rank sums. Technometrics 6, 241-252. 14. FNieshwerY,oRrk..A. (1985). Statistical Methodsfor Research Workers, 13" edition. Haffner, 15. HfoarzAanradlyEsviasluaantdioEnvaDliuviastiioonn,ofStSaunbdcarhdroEnviacluaantdioCnhrPornoiccedEuxrpe,osTuorxeicSittuydiPeotsenPtaiyanlt:er,GuOi.dEa.nce e`Wtaaslh,iUnngtiotne,dDS.tCa.,tes2E0n4v0i6r.onEmPeAn-t5a4l0/P9ro-t8e5c-t0i2o0n.Ag(eJnucnye,1O9f8f5i)c.e ofPesticide Programs, 16. Risk Assessment (XI/283/94-EN), oChfaNpotteirfiI,edSeNcetiwonSsub2s.t2a4nacnesd.2.T2e5c.hn1i9c9a4l, Guidance Document Company Sanitized. ees Does not contain TSCA G8 H-25425: Repeated-Dose Dermal Toxicity 28-Day Study in Male Rats --~ DuPont13830 -- TABLES = -_-- `CompanySanitzed.DossnotconTtSaCAiCBnI 216.2:5D4a2y5:StuRdeypeinatMeadl-eDoRsaetDsermal Toricity Abbreviations mg=/ mg/k kg/g day gan=mgra/ms/adnimaaliyday TABLES EXPLANATORY NOTES `Summary of Hematology Values RBC - redblcoellocodunt HGB - hemoglobin HCT - hematocrit MCV - meancorpuscularvolume MCH - meancorpuscular hemoglobin MCHC - mean corpuscular hemoglobin concentration RDW - redcelldistributwiidotnh ARET - absolutereticulocytecount PLT - platelet count WBC - white blcoellocoudnt ~ ANEU - absoluteneutrophil(al forms) ALYM - absolute lymphocyte AMON - absolute monocyte AEOS - absoluteeosinophil ABAS - absolutebasophil ALUC~ -- anodbataslarogeulnstuaintedceell SummaryofCoagulation Values PT - prothrombintime APTT~ - activatedpartialthromboplasttiimne - nodita DuPont13830 - rv `CompanySanitzed. DoesnotcontTSaCAiCBnI H2.82-5D4a2y5S:tuRedpyeianteMda-leDRoasetsDermal Toniity DuPont13830 TABLES EXPLANATORY NOTES `SummaryofClinical Chemistry Values AST - aspartateaminotransferase ALT - alanineaminotransferase SDH - sorbitoldehydrogenase ALKP - alkalinephosphatase BILI - total bilirubin BUN - ureanitrogen CREA - creatinine CHOL - cholesterol TRIG - triglycerides GLUC - glucose TP - totalprotein ALB - albumin GLOB - globulin CALC - calcium IPHS - inorganic phosphorous ~ NA - sodium K - potassium CL - chloride PFL~U -- plnaodsamtaafluoride Summary of Urinalysis Values VOL - volume UOSM - urineosmolality PH - the logarithmofthe reciprocalofthe hydrogen ion concentration URO - urobilinogen UFLU - urinefluoride UMTP - urineprotein ~ - nodata Clinical Pathology Note ``wWehreenpearnfionrdmieviddouanhloablsfetrhveatrieocnowrdaesd vraelcuoer.deFdoarsbeexaimnpglele,issfthbialniraubcienrtwaaisn vraelpuoer,tecdalacsul<a0t.i1o,ns0.05 `was used for any calculations performed with that bilirubin data. EE `Company Sanitzed. Does not contain TSCA CBI 3 BONE EEEEE Nn 2 53 3 3 3535 35 3 353 ng of sf af of ef wf 4 ai <8 an gSH # =< gd gd g7 33 84 % Fd 8 2 --_ ai fs ss os ese a2 2 8.8888 88 83 . Eeg e P FEuusagtasaaanngge) z : I i $i8 22 --~ 242] Sz mo 22fg23 9%i7%r+8rof eagogl 4% am ne ed gt 3s 8 87 37 RN og &% 8 B38 ER og ii He . Li?yis : id : : GBiilfg:e s5 pFF33i 0B34:8 7 dF 3 3&8 ||;8 H7 Pi FI Gompany Santzed. Dnootconstain TSOA Cl ~8 2 ~ :z i IE j1x3 ~i Rf mPa 2 2g pe 83o5f 3oF .AD3o3f o2f 3WI WS8e3i 3ok : gg a 2 fiigrrr s 5 5 5 5 3 3 3 5 = : Ewg e SEGA g HNENWEER i: ? =2 31 a 8 8 8 8 8&8 8 3 8 8 2 BREESE ii Z FT 89 89 4 gn ae a0 dd dd ge ae if ii i8 : EEf ERi 8E8E8: E8E8E|Edi 2: 3 5S3v%e 2F 5& #2 03# 0%# 5# %2 08 Zg ||4,%42% i: Company Saritzad. Dos ot contain TSGA Cl ~ : 3538g Bd mEas 2 HY dH 3% 8% ge gd : -- i!3g- 3 2 a 8 3 se a ] 2i. a : re im8mEa3 El8E3egs Zfislg a 3 s Z 5 < !FF3 33 i i ~ 234 reid 3 Le H58ET3 F E3 E1RE3 i 1: 8 82 & 2 Z 3 i bii ; J CompanySanitized.DoesnotcontTSaCAiCnBI ~3 2 g H2.H2EE8 E8.E8 ggkB88 353d ds dd d 5 .5:% 23 52 of 38 oF 98 3d 8 3288]! Zae ~ ' - 22 Ha Sc oo oo 8 oo ~~ 492 5 5ER3IM E 8 F333E aE 38 1%ji 2 i2 1 3i513 ~&be 49] z ii = 22 I _ iii 5 3 53 3 3 i I 8dss8 8= 75 % %sz | 83353 5888 A 4 i i 2s i3: 1 [-------- ~~ 3 3 z 22 g #82 "8 wey ce :g rz oz WE s- io: - z fz 23 ~ it - Zz 4 25i ivotr 2 : usr ee oe am an oo 23 2 Z x me PN Sq am am ii 2 REREEE ~3ii] I wli d Hbe pHidpd,ooia sper ~3 : 2 ar 2ge2PoE3 JE Flak EEE LE -- & Fg8 28: zhi SEL El gz o3i iiiisi: S& o: E5 E[E;53 sls ~alf2d 1 ? ih i ite iE1l 11:fF. H3 fihlsSg ~ 2434 HliEsh iffu `i CompanySanit, ossmotorsTSGA GB ~~ sg 2 ggE r2 g == ee iLI 3 se =n eo 2 2 2 gE 2 z FA 3 ME Z g8 g is w a = 2 = am = Pa ~ 83 4 . f 5 313 i3i3 "3 ~ 8] 8 usa 2 g3 mee ge 33 mn E5E g uc g: nme gz Re E g f8 3 2 23 om 2 PEEL BR BRL PoroF Fr Fb yp 2f%ig8% of 3 o d3g i EEE IE FE EE FE Hoag hi i Forof kor GompanySaitzsd.Dossnot conTtSaCAiGnl ~3 ~ Hoi& 3PE i3 ~ 23 2 EE sz g si 5 2 3 "nem od HH iE gE: mom |g 2 i $s i: 3 iE3 gE=o:r Fs CE CghhEed &2g maz ne a fis iHsHd 5 EE ERE: lal : E55Ha bi ob8, ddiR: Splyo gidMdiHdngaoh qo ME $:3 13 L5 FBH] 2Ri Company Sanitized.Doesnot contTSaCAiCBnI 2H.82-5D4a2y5:StRuedpyeiantMeadlDeoRsaetsDermal Tonicity -- DuPont 13830 TABLE 7 PERCENT SURVIVAL OF MALE RATS Group: x Dosage (mg/kg) 0 x1 xm xv 10 100 1000 Days on Test 07 110000 110000 110000 110000 2114 110000 110000 101000 110000 28 100 100 100 100 `Numberat studystart Aliveon testday28 10 10 10 10 10 10 10 10 Percent Survival = (Numberofrats alive/Numberofrat at risk)*100 Numberofrats at risk = Number at study start. -- `There were no statistically significant decreases in survival. -- - `Company Sanitized. Does not contain TSCA CBI 2285.0D2ay5:StRuedpyeiantMeadl:eDoRsaetsDermal Tosiciy -- DuPon-13830 TABLE 8 MEAN PFOA CONCENTRATIONS IN MALE RATS PLASMA PFOA (ppb)* Dosage (mg/kg/day) Mean SD. n 0 <10 00 10 10 <10 00 10 100 13 2 10 1000 105 2 10 nSD=.n=umbSeuronfdsaradmpDelveiastion ba VLaolwueerolfim1i0t wofaqsuuasnetdatinitohne(cLalLcOuQla)ti=on1w0hpepnbthe concentration was below LLOQ (<10 pp) --~ --- ws Company Sanitized. Doesnot contain TSCA CBI H-25425: Repeated-Dose Dermal Toxicity 28-Day Study in Male Rats --_ TABLE9 MEASURED CONCENTRATION (ppb) WHOLE BLOOD FLUORINE Dosage (mg/kg/day) Mean n 0 <500 ppb or ND 5 10 ND 5 100 <500 ppb or ND 5 1000 <500 ppb or ND 5 Nn=Dn=unmobtedreotfescatambpllee=svalues < 200 ppb Values "lessthan S00ppb"are > 200 ppband < 500ppb. 500ppb =Limiotf quantification (LOQ). --~ DuPont 13830 --~ - `CompanySanitized. DoesnotconTtSaCAiCanl H282-5D4a2y5:StuRdeypeinatMeadl-eDoRsaetDsermal Toricity DuPont. 13830 TABLE 10 SUMMARY OF HEMATOLOGY VALUES FOR MALE RATS Group IX Omgkg Group XI 10 mg/kg Group XI 100mghg Group XV. 1000 mgkg RBCDA(xY102%8uL) 731 7.16 7.07 7.18 0.157) 0.259) 0.260) 0360) HGBDA(gY/d2L8) 146 147 143 14s HCT (%) 047) 049) 059) 049) DAY 28 413 467 457 457 15(7) 1.409) 170) 140) MCVDA(fYL)28 6438 653 646 6.7 MCH (pg) 200) 1.50) 110) 1.60) --_ DAY 28 200 206 203 201 r MCHC (g/dL) 0.7(7) 0.609) 0.509) 0.609) DAY 28 309 315% 314 316 0.67) 0.40) 0.49) 039) RDW (%) DAY 28 1s 1.6 nr n2 ARET (x104L) 0.67) 0.4(9) 090) 030) DAY 28 219 95.3(7) 2644 58.49) 3020 140.79) 251.0 55.30) PLT (x10%4L) DAY 28 1264 na 1210 1242 WBC (x104L) 2602) 177) 8168) 1268) DAY 28 1485 13.80 3.1107) 2.5009) 1431 24109) 1384 22309) ANEU (x10%4L) DAY 28 249 215 225 197 ALYM (x10%4L) 0.95(7) 0.46(9) 1.0209) 0.400) -- DAY 28 1150 2.937) 10.86 2.0609) 132 1640) 105 1990) - Company Sanitized. Does not contain TSCA CBI 2285.0D2ay5:StuRdeypeinatMeadl-eDoRsaetsDermal Toriciy -- Dupont 13830 TABLE 10 (Continued) SUMMARY OF HEMATOLOGY VALUES FOR MALE RATS Group IX Omgkg Group XI 10mglkg Group XII 100mgkg Group XV. 1000 mgkg AMON (x104L) DAY 28 039 032 036 042 AEOS (x10%4L) 0.08(7) 0.1309) 0119) 0.119) DAY 28 020 0.15 013 ols 0.1007) 0.069) 0.079) 0.0409) ABAS (x10%4L) DAY 28 0.08 0.09 007 0.06 ALUC (x10%4L) 0.047) 0.059) 0.0409) 0.029) DAY 28 020 023 017 019 0.147) 0.1209) 0.1009) 0.05(9) -- Dumamngedas: Mean Standard deviation (Numberof values included incaleultion) + Statistically significant differencefromcontrol a p< 0,05 byDunnetyTamhane-Dunnett est - a Company Sanitzed. Does notcontainTSCA CBI H2.82D5a4y25S:tuRdeypeinatMeadl-eDoRsaetsDermal Toxicity --~ DuPont.13830 TABLE 11 SUMMARY OF COAGULATION VALUES FOR MALE RATS Group IX omgkg Group XI 10 mg/kg Group XIII 100 mgkg Group XV. 1000 mg/kg PT (sec) DAY 28 APTT (sec) DAY28 155 0.5(10) 180 1.6(10) 159 0.6(10) 187 22(10) 156 0.510) 1.5 12(10) 161 0.8(10) : 188 19(10) Dara amanged as: M`Setaanndarddeviation(Numberofvalues included in calculation) There were no statistically significant differences from conirol at p < 0.5. ~~ PN -_-- `Company Sanitized. Does not contain TSCA CBI H2265-4D2a5y:StRuedpyeiantMeadleDoRsaetsDermal Toricity -- TABLE 12 DuPont 13830 SUMMARY OF CLINICAL CHEMISTRY VALUES FOR MALE RATS Group IX 0mgkg Group XI 10 mg/kg Group XII 100mgkg Group XV 1000 mg/kg ASTD(AUYL)28 12 122 106 108 3000) 22(10) 20010) 23(10) ALTDUALY)28 52 st " a7 SDH (UL) 7010) 9(10) 9(10) 11010) DAY28 18.6 7.610) 15.0 7.010) 19 2410) 129 4610) ALKP (UL) DAY 28 212 20 205 244 45(10) 47010) 4310) 51010) BILID(AmYg/2d8L) 0.05 0.06 005 0.06 rm BUN (mg/dL) 0.0010) 0.02(10) 0.00(10) 0.02(10) DAY 28 18 17 15 15 CREA (mg/dL) 210) 2010) 2(10) 2(10) DAY 28 029 0.05(10) 026 0.05(10) 024% 0.02(10) 022+ 0.03(10) CHOL (mg/dL) DAY 28 [3 4 43 30+ TRIG (mg/dL) 11010) 710) 5(10) 6(10) DAY 28 a3 4 36 31 18(10) 24(10) 1300) 1300) GLUC (mg/dL) DAY 28 13 104 101 107 TP (g/dL) 2810) 12010) 10010) 1810) DAY 28 61 6.1 60 60 03(10) 0.4(10) 03(10) 03(10) ALB (g/dL) DAY 28 41 a1 a1 a1 ~ 02010) 03(10) 0.110) 02(10) -_-- `Company Sanitized. Does not contain TSCA CBI H2-82.5D4a2y5:StuRdeypeinatMeadl-eDoRsaetsDermal Toxicity DuPont13830 TABLE 12 (Continued) SUMMARY OF CLINICAL CHEMISTRY VALUES FOR MALE RATS Group IX omghkg Group XI 10 mgkg Group XII GroupXV 100 meg 1000 mg/kg GLOB (g/dL) DAY 28 20 21 20 19 CALC (mgdL) 03(10) 02(10) 02(10) 02(10) DAY28 14 0.710) 12 0.6(10) 11 0310) n2 02(10) IPHS (mg/dL) DAY28 1.9 12 104 107 22010) 15010) 0.7010) 0.6(10) NA D(mAmYo2l/8L) 1472 1476 141.7 1482 K (mmol/L) 1.7010) 23010) 1.6(10) 18010) --_ DAY 28 6.41 625 6.05 5.80 0.65(10) 042(10) 0.45(10) 0.3010) CL (mmol/L) DAY 28 1023 102.6 1032 1042 PFLU (ug/ml) 2110) 1.7010) 13010) 25010) DAY 28 ol ol 01 ol 0.010) 0.010) 0.010) 0.0(10) Data amanged as: MSteaanndard deviation (Numofbvaelures includedi calculation) + Sutistically significant difference from control at p< 0.05 byDunner Tamiane-Dunnett est --~ -_-- ae Company Sanitized. Doesnot contain TSCA CBI H2-82:5D4a2y5S:tuRdeypeinatMeld-eDoRsaetsDermal Toxicity --_ DuPont 13830 TABLE 13 SUMMARY OF URINALYSIS VALUES FOR MALE RATS Group IX Omgkg Group XI 10 mgkg Group XIII 100 mg/kg Group XV. 1000 mg/kg VOL (mL) DAY 28 90 72 12 8s UOSM (mOsm) 5.0010) 4510) 5.010) 3.410) DAY 28 1069 1461 78 924 691010) 662(10) 407(10) 346(10) pH DAY 28 75 74 76 74 URO (EU/L) 0409) 08(10) 0.510) 0.5(10) DAY 28 02 02 02 02 UMTP (mg/dL) 0.009) 0.0(10) 0.0(10) 0.0(10) ~ DAY 28 0 ne a8 59 35(10) 599) 3310) 33(10) UFLU (kg) DAY 28 80 7.1 8.1 80 2910) 2.010) 1.6(10) 1.610) Data arranged as: M`Setaanndard deviation (Numofbvaelures included in calculation) * Suisically significant difference from control atp < 0.05 byDunner TarhaneDunnett est. --~ "4 Company Sanitized. Dossnotcontain TSCA CBI ~ 5 z 3 SS gd ns EE $B|13ig 8m%1i833la8%8 :B 8o8a #E o 8 8%a E82 Csi gad : Bana # 5 gi 5gg3 g 8 32 { EE :| Rl gg 54% 3 4 da tid wlll R &| OEE BE BE jit Lit iii]a f& ~~ B 3 2 1g 37 ii cf 1EooeEE- rme- --i B igTi[ig 2a.%i8sf%ee 8582d3! ire g HjejmETmER Ed iZ ETE iTse ie fle Brie Zzz TTT TTTTs | |gd| i12gg agEi|OF81&8 i jiE753Y _ 5 ET iE $ gz | i: : Tggi ii iiz eg i; 5 | i liz is EERE OE RENE 5 ii I33 49H] ~id ] || iI2 ifo CHE iH Poa o% 2 iH {Eg Ef Egat i pepa e4% afail8 14g 7 Hl F i C EBClIdE, ON ~ 1 2 i357 122 1 2 - = -| if FER 2 ER gH lgigiiBes Be fiFgisTkei(2.72.R .0 : i eli 1 2R i 2% Lg gfEE i ii5h3 EEE {aq --~ EFzE Eg> | fi:i hiHstEd :# 2 gi i iis E- i I g || i 5i8f Z | 1:5 s gZi| PoE EIE iiE 2332 i 34 ~ 3 i; , ji g8E iPTg i (fgRiifgiiii(:48 iEEEE i18ne T10E5R2Es iad inf ig Compr, Smo ~ 3 3 - Eh jE go Z0 I SE B Ea if ot ig 8 zs oi: g Be Em mA BTR ~ =E8e iiB ; 2 3 ' 5 | IE if hadi kod : H gzi |Log 4 5 35 iff fl F2]! CLoodwHe ihoEaddtbog ognH i 8 Cdn dll oH i41 LSI RgigaBiRnE [EDaEoL H3 DPoorEo SFtog2a% gisl 3 i 5 ~ 34 TT EE Company Satan. boss etsatanT3CAG1 ~ 3i: 2 2= ig! tek ls Z iF iB 2 Eh ERIE = i Ere | ggEblT k r oE T 8 iy igi ~ | g8&88 ii | iHgHd %. g 21 i i igi in it : | LPog rry og B |: PoE x io Loft oa I|o mii iHf43 Z CCo oE r opii a Ht aT lo ae kSa EaEl:dGL ~ 13 ee =| Corts, one TonG8 ~ 32 : Z gi Bm jE E- : zzga E | Ep vo 4 . Ii Sk : E : {33 SsEHzH I LI kiiad * 3 5i i i3E } :| iE iff i gi WiHoi ogipOF 5 PR EL : H i EEk TR dat oak rr od --~E3H4 88 ik reE d ct L ia|E SAwon pean H2-52-5D4a2y5S:tuRdeypeinatMeadl-eDoRsaeisDermal Toxicity DuPont13830 FIGURE -_-- CompanySanitzed.Doesnot conTtSaCAiCBnI 2 2 ji 3 toh J SE :| 4 i ] EE 5 ~ &3 \\ |I s 8% Tf 5 = (3) wom Apoguw H2-52-5D4a2y5:StRuedpyeiantMeadl-eDoRsatesDermal Toriity DuPont13830 APPENDICES --~ -= Company Sanitized. Doesnotcontain TSCA Cal H-25425: Repeated-Dose Dermal Toxicity 28-Day Study in Male Rats DuPont13830 APPENDIX A INDIVIDUAL BODY WEIGHTS - s___ `Company Sanitized. Dos not contain TSCA CBI ~ gl. $d. %3 Co3b mmm EHBEINARCE smiinogsinzes i1: mEnEEEEn = jihie mEaEs ig dE i.) 3dssaiiass :gz :rk nema i5 3i3 Ad ~34l i Elfg3 i sssmmvanns g CompanyStd, Soe ronSaGAnBH ~2 8] <4 &z 2 3 i 2 :1, Fi2s E aH : i IEEe! r noe mnng snsmnenas COSA Dob ~ gl. 2| fs HE Hof mpmam & 4 FREE . 3 ER3NERRENR ~ fh, 1:7 EgRErRReEReERsR iTEi Hsiedmdaen gl iod .y gBiRiEdIEAdgdaaaccie Hof i BHP fo nme "z AANASNRRRN ifn. _ 45 =&| & ; 355385882 # aaaadaanan # [oS ---- ~ gl. H3HEEiHS it i i 5 fle g :2 1iiz ~ 34527S =&| & |5i2..8i:Iaamdnsniadneideaann: i3 ssazsssses # Anaonmonns [A ---- ~3 al <i iii i3n T fa se a 37 A383RREEAE i3 egsSdeindednaodnisd grooms Io mmm PS 15Plgego FaRmEmEaR *5 peor . %3 81.7 gBrasnsmcessEanmsnse 5 = zg , Hao EIN oit g i i 3.=0; SBaRnGsRnRsAsRsIsNsS Lemma 1 7 13k%3; SRIRIRFERR CE Sob ~ 3= i PN f i i i :zg 3 ; 243 ~z8l t 8 8 igiaddads 4 s3g3gzznss=ggsssEess : [-------- ~8 %| 5s 3x GFLoIpEiR Seddnsesng ifo aogmnRmimEsnngg if sTenmi 1b:7 8m858m535m885 iii RDEdogEmRasRne . f 1 i 2 rn 71In | i jediidaias 3g AIRIINRILR . ne 3fo SARRrRdAaSsIsRiAdEeR La8 man i y HRREENREAE | CompanySanitized. Doesnotcontai--n TSC--A ~ . El fs 3 2 Hi --_ B i i g 22, ii g,EF ib:s i:8 g 2 242 I ix ~z8| noneenans zgzndsans spazsssass BRRRA%2as3 CompanySanizad.Dossno contTSaCAiGnBI H2-82-5D4a2y5:StRuedpyeiantMeadl-eDoRsaetsDermal Toxicity --~ DuPont13830 -- APPENDIX B INDIVIDUAL FOOD CONSUMPTION ~~ e EE e ------ `Company Sanitie zed. Does not contain TSCA CBI H2-62.5D4a2y5;StuRdeypeinatMeadl-eDoRsaetsDermal Toxicity ~~ INDIVIDUAL FOOD CONSUMPTION EXPLANATORY NOTES Abbreviation ganm/day = grams/animal/day DuPont 13830 --~ -______e Comp_ inySanit_ ized. Do_ es notcon_ tain TSC_ A CBI ~ f. Za H ~ 1 Piin smnaam I He 33 3 | Be mma 3] ir 2 asmmanqenn i83.; diiRddaAsa $ Somos signs ~ gl, FH & ~i ; 1 Ll 1H ii i $3: S3gEsTTIND 333i HE fen. 38 i: com, Sete ~ 9. a is FH aa ~; i g ! sip Qs iz i hhis ads iBie amma oe i mmnEE ili, =x is Franancnaas ~i3| 3 amaemene 4 Company Sanit. Dos nocontain TSCA GB $ -i z fhno apg fz iBe5 mNAeRRRaIRRnIR 2g i FERRE Ha i e i Be 3 mms 348, i : Company Sanitized. Do note conts ain TSCA CBI H-25425: Repeated-Dose Dermal Toxicity 25-Day Study in Male Rats --_ DuPont13830 APPENDIX C INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY RECORDS --_ Et --`Company Sanitized. Does not contain TSCA CBI H.25425: Repeated-Dose Dermal Tonicity 26.Day Study in Male Rats DuPont13830 INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY RECORDS EXPLANATORY NOTES Note Clinical observations reported in this appendix were recorded during body weight collection. Clinical observations recorded post-dosing are not included but are reported in Appendix D. --~ Company Seanietie zed. e Doese not ce ontaie n TSe CA C8. 1 2 ~ gl. 3 ii ac LI Ios . g cFssdasislicsionsiag "i : EE 3 1 &: FI 8 LE 8 $ g :g :g PEP,300i8D 0 bRiEsF 1gir4100.d Pp, td of asd 23; 23 PJil lsE rirbapneidiiaaadoahya il i Fiaiiilididesiiiiidsg Eloi. ss . . i 3 8 ES 8 ES 2 338 i: 8 I] 8 8 ~387 i. = == = = CompanSots. SctcnTSAG1 ~ g, aBixs i aw sien datazaiie i i iift 1P4i i2 EY 5 gs 2% 2 23 23 Fl jfregiriiapidigigiipiiyd 3i3 SfaiSiiiiiiigidbiisiisdgs 3iz 5 : 3 i 23 [PR ------ ~ g, i pieiledetaiiaa lina, : [EI 11 113 A : 5188 2i 8ii3 i g iii Cl ED DEiL foY p 8d1t Bgy r g10d 2 23F 2 2 2% = 2 |Fl sGrfiifdnirziizdfdeiisiiaeiliiiiliga i PIRREeEaEsRREREEBRiEsEdEgRiEeRaRiEiRiEty 33 gs 8 El ag o$ r = ~E3l] = = 33 aa ox == 3 :3 & aa % or = FE Company Sanitized. Doesnotcontain TSCA CBI HE aig i --~ : fro 3ii8 1g % ii 1 i 2fF 2 2 :zg i$ f8 iy8 ni5 in3ndg5,a3 iH ~ 35 85 ERE z: :tT 2oz 2CC ow = x= 8 ' CompanySanilzad.Doe ot contTSaCAiCanl ~ oFsi i ae i --_ Mi ine os 11: : 354g i3 ii $ F 8i ARE EE Poi, P40 i, 0F ii de 1i by i, o,gy3 . P RfeERilEEpRE gtEEiiR,pEdtpi g, i 2EdR i EayRRE0 g frigfriiniiiciiniict jis, RIEEReErEiRiEiRiRiReEeRiERiNlEiiRaEiRlEd 52 ~3F gq un -- 5 8 oe LE uo ------ ~ gq. i ; -: Tyj,ie FEI,E z f2sfiilaie5 c1itjg& isaigi2 zii3giesigi2inisss :She dfejiEisliildieyiiiilail ~ E=3zR45 5 EF = . =g ig * CompanySnes. Sos otcnain 8G GB ~ i ac i i: , ~ a 2 [iI F iT f! : FfTF 1F3F 3 ' 32 && & & 22 2 iiiro3ii1 gE 2 2 ii;y 1 1 g[I idi 23 2% 2 z E23s8i3 %,i383f8i8 ri2g8r5 ia8ibf%ani8% z : Phi iz IREERERRERERRERRRERREE i| 3 3EF 3 Fz 30&8 :8 38 zi ao& Z & 2z z & = & Caran Sanont Bova ComaTIRARY if | ae | : : ~~ 3 il 3 38 1 8 i 23 i ~ iF =8[& i: fi2s2ig2s fizig 3g 2 FC = = Sg CompanySanitized. Doesnot contTSaCAiCBnI H2-82-5D4a2y5S:tuRdeypeinatMeadl-eDoRsaetsDermal Toriity DuPont. 13830 APPENDIX D INDIVIDUAL CLINICAL OBSERVATIONS - POSTDOSING TT ---- Company Sanitized. Does not contain TSCA CBI H.25425; Repeated-DoseDermalToxicity 28-Day Study in Male Rats DuPont13830 INDIVIDUAL CLINICAL OBSERVATIONS- POSTDOSING EXPLANATORY NOTES Clinical observations reported in this appendix were recorded daily after removal ofthe test substance. Clinical observations recorded during body weight collection are not included but are reported in Appendix C. - =. `Company Sanitized. Does not containTSCA CBI git mEsdRaniRa.drnidna ! ~! ; : id ii! PP: ogi& i3, &$22 i3& g, jail ng i ii P3 ifi4ri adlSiieigage2i%agT ge teislg Sz ogbgElfr e f 3afledr fHfiytgeAa sdi2E4 Enit E:e. is Fii sti 3PRER8L3% 3E% RI E t$3ii8 es t5 i |El 28 ~#T 5. z 2 : \2 \8 \2 - . routes bogmemsrntn ~3 33%, 1i 2 ~i 5 ( i Eos1b3i 8 3i 4 3: 3i ' ISoogty} g1tyid ipda,il r1 oni P: o"i8g%drfg2gd agfg2:i1%ia g2rafye z : gPEhriieiigpiilbo2sboga bdiiiilb ecd oa g t3ri2g gd iis FfrEeRiRiEgRe frialdeds tfoobiys ifcid HT - ~3F LL . . .. RS, omar SO ~3 Sls Ef ag ERR IR RG i i --~ i i 3 :2 :g 1 log F i; f1; ii i Ebr hd feos 8: g 53 3iiogi id R3 i:1 2g 3 IS! FM 22 ix = 3 ' Gomany Santzad. Doo otcontainTSCA Gl His i EE] EE 2 ii ~| i iif f: Lid,ioi 5 3 PgoSagEebEiRrifIggeiiitEagEFgd iUiifHiat dfEHvar iiEi 23 $8: 3 384 difiiii oRiy oig i LE : "ls. } ~3 s- . z3 A .. Sor mms ~ gl. F3E% 2 i i -- i o IP PE A A 3 3 33 3 ' : i i [I i EINS E EA RE ER zPogly gE 3 sEbl 00493 y; 3p2 3Ef iSy9Eg4E 3di(3ia4233 toly ggdi,s dspd,e d5p4,e d(1i8r; bsihig;s f I 4 $E8E300 8 tf (3 if :i1 218dsdd3 2i2933%1 8i8 3 in. i is 5 gg 2 8) E-] a a a a ~ 233 5 = = = = = Company Santzed. Goss notcontain TSCA GBI ~3 84s ii &2 gialad i --_ 3 {og c5 oig di, Poging 2ii 8i414:%23 i is 5] Zo |f ~ FL EHH i= Company Saitized. Doosno conTtSaCAiGBnI ~4 il 2i 2 -- 2 5 Py 3 3 : HE ; Eo EI iVPoosgdFrFga Sg |oibioesedrs 4, REE Ef 2 2 fg 331 fies Doy ag$esdtd.iaidfi8iiiagteedlfiigdydg iBiiEbiisriiiaggiiiiiiiiic HEH INS 5 2 558 id is 3 2 2 jE an a 2 2 om i: i i 3 ~HF : Coy. om tS ~ 8. 33. 3%ia2 Eamiiiiiadia liad : 2 iii 3i iLk2 3:g 3$iy gf2 : PPog 0ladtfCrigfiaiiezireg4iitr,afaiiit2iitnkayd TEER HL FON EEEER RIERI NIE N 33 iz i EZ = 5 g 5 2 e 8 85 3 fs 8 5 3 g ~24]% Fe ox = = = = CompanSots. Se retaminTSCAG1 -- gl. 23s 54 i 1i i ' I3l 33 El 4%| ~2&ll ; : i: |3 P prog F5 oa$fig 2gEtig feild i sd i10i 0% is sz i2 a 1HE i i = * CompanySanitzad.Dosnot onaSOnA Gl ~ 4g, i&2 i i iy 2 Sid HE 3 3 i : Pioi,ridi i, f1 r t$a1h P EEEyigr tf a i 2 ifF l aFiia dsi P| dPirEdpfdprfidPsssflfppieiiiiiifligg jr 5H3ER EIEE| E R4R4I%E CG ERiRiEsI8E4E4 8 i ig 3 5 2 2 sz 2 2 s g EET $= Ee - =k & Company Sted.Does conn TSR Go Alia it REAR ERE ER RE ERE g 2 -3 4 Eo 3 3 3 2 ' F8 I i : f i :$ pl ir boar be Fill oandge g r ogid i Fa bis dois dotis sd &1 Sab, P8r4 P5 o B8egb b5 a8b: PPI RIELRI E2 iTgE BgEg GBEo E LEDER GEG i 1s : : :: | 9 a a % 2 _uf Ie B BE 2 2 CompanySatna DostcontTSOACEI H.25425: Repeated-DoseDermal Tonicity 28-Day Study in Male Rats ~~ DuPont13830 APPENDIX E INDIVIDUAL EDEMA AND ERYTHEMA SCORES -- -es `CompanySanitized. Does notcontTSaCAiC8n1 12.82-5D4a2y5:StuRdeypeinatMeadl-eDoRsaetsDermal Toxicity DuPont.13830 INDIVIDUAL EDEMA AND ERYTHEMA SCORES EXPLANATORY NOTES DRAIZE* SCALE FOR SCORING SKIN IRRITATION Evaluation of Skin Reactions Score Erythema and eschar formation: Very slight erythema (barely PErceptible) messes: 1 WABI SYMONS mmmlrmmmsm-- 2 Severe erythema (beet redness) to slighteschar formation (injuries in depth) ....... 4 Edema formation: dR smsmgsm----S---- 0 Very slight edema (Darely PErceptible) urns 1 ~~ Slight edema (edges ofarea well defined by definite faiSing) ............. 2 Moderate edema (raised apPIOXIMAtEly 1.0 MN)... 3 Severe edema (raised more than 1.0 mm extending beyond the areaofexposure) . 4 a DErdaitioarsi,alJ.CHo.,mm"iDteremeoalftTohxeicAistsyo.c"iAaptpiroaniosfaFlooofdtahenSdaDfreutgyoOffCfhiceimailcsaolfthienFUoniotdesd,DSrtautgss,sAnudstCions,mTeetxiacss,.1T95h9e, pp. 16:59. -a Company Sanitized. Does notcontainTSCA CBI ~ 3. i2 5: i be gg: i: i: or i i: - ii ii& li z i: or 5 i: . HE 4%) | ~ 38 in sasanmnnne : i doverSg, wispsteh aF i bi AE a eeeeeccees EE i 3 Tree |i & i: ;Poia: eocococons - ii: yy eee g ii i: 5 2 seesssense i Ir f= a Eee am iq |33 8 faIP 2E-- HH ssnemenne 3 CompanySats.coesot oma TSAGH! HE az } ii i 3 i 1 ji, a Jl ~ 243 i: (1 iF . pio < Ii SR. Comptes Smt ~3 a lbs alis = ecccscccccn = J-- LI i: hi ~ | iii 2 Ie so0s000000 BFyE;R oo i: iz ISih poa cee Campari, oe eco TA p Hop TY a - iFg i: oococeeeses s js tii -- g i; ~~ g, il: alas i i --~ :i: : 3 > 2 : Gl ~245 =&|& i: roi, izx ccocecosce fa 33338858 # addaaasass Company Sats. Docs notconan750A Go il fy TTT ~ | ins : fyili . FE 3 ii ay li: a hi gg ~i ; ihe fg i fig ~~ i ! ~ : i i: g {3 tC I EE IiEs 8 ~ 23% =8& 2 E sesescsese i: 4 z3zzsesass 2an22R3R3T : CompanySanitzed.Does mot conTtSCiACnBI Ho i: i: 8i 8332 TS 2eeRs ores ~ | ils i ii: sesscsscoe i: . i: 2 eeccssscos i i: i ii Soe = BF ~ %4[F z=&| 8 $ z333888883 BARARARNAAR : i : Sonoma rama =ogg io=2 ee pi ~~ TH 3 hyo iE: 2 ecocceccss ~8 ! : 5333525283 ~3 34 i i i ~ ;i :. f 3 3 F2g 1 a8, ~ 3=&4[ 78 i: g3z & 5 fis fi: : Rs2s2a%z3s9s4sae2e4s Comper Santis. Down omaTOOATEY gi #1; Ea i: pee ~ 15d Fp, eeeemeeeee igf il; fo eeeeeeeees 2 1i .3 eocecscccs i ~&43 HEE ssazsnnne: 5 ConprySots. bos ekcoTmAaGOI HE22 i g io # 1 I Ifa I ceesssanes escccccccs cococcocce i2 Fi i12 cecoceccoa ooscccees pif i i = ccocccecce ~ 3818 is jad zifs eeosccccoe ILHl LN & TE eZ ~157 =&|& isl fo ccoscccccs fSur ceccoccoe FizFI. # 8883238883 Company Seniaet, Dossrot contin THOATE! 1 oe ~ 3 ! - i 1qd ~ 3: fs cocececces i: i: ceccscsocon i ssszsmnnns 5 GarySet. oR Boi ri ii 3 jifg. coococoaee ~ 381 {ii i 2 Fl. coeeeeeees eeeccccces HI2: iy EE a2 ~ 548 =8|& f. cesccccces fi o: ceecosoces oi: f=of3 oooooonee HE $ sszssssss -EEEEEEEEES ) GompanySantas.Dos ot contTSaOAiG3n1 ~ og. BE ogiai cecocsecce ti bE fa occccccceen 3 pi ~ 1B5l4a eommoeoees jiiQ:s coccccesce {2 eecesccces 5 i: P| i nb Il 8 i al --~2&% ak eeeeeeeee $ szsaspmzmemeasneesse 2 CompanySated,Bossrat conTSaAGiEN ~ EL if ae i i i ~ 3 i Is oococeccen i: i f 2 cecccccecn a15 i: ~23% =8[a $f8a ccococccess fi2 gT ooscosscoe $ szazssases # ad@azagass 8 CompanySantiad. BosnotcontTSaOAiCnl ior 35 2 Ek ad i 3 BE i . HE fo PE ceseccccce coccoccess cecooscces pit Bf. cececccece ~~ 3:18 jd Fl, Rd coeeeeeeee 2 if & 1 I -- 3 PE 3 a2 Fig ~ 57 =8[z # n3n3a3n3m8aa82528n2k meres oo lS Company Sanitized. Does not contin TSA CBI ~ g. ili al%s fa ios cccccccees i : eccccccscs gi iz pif ~ 3E4 367 5d ik cifu 5 HiS o Si fo eooccccces eeessenee | fa 8 coscncoeee 5 Fag 3 Corp Snes, os aT50A 8 ~8 i i i --_ 3 4 z 2 ol i" ~ 13% =&[ 2 1 5 ecesccccss i3 fg ceccoescos fg ecccccoccos 1x cccccescon ggszsssess RARRRERRIR Company Saritzed. Does ot contin TSGA Gl ~~ i. HE 1 Jo FE bi ol ~ | ih i $1. iif tl; emeeeeeeee " eeeeeeeeee z 3 Ie Li HSRO1sgBE ooo : ' Compony Saran BonninrT TSOAGS) ~3 gHIEER foie $i fg cccccccscs Pa cescescoss ii fr eeccocooee HY Pla cocemenene 3:> pEeltz cocoscoces ~ BEd iffis EE ceocccssce FE fa eescoscons i: & 2 io n fu occccceccco im oii 0 i 53253] fouggB oeecoccces = Company Sanitized. Doesnot contain TSCAC81 ~3 alis il i ~ 3i 3 z Pi 37 iI] E 3 EPie EiE 3g? oomeescece a2 243 FE gmazmeszas : Comm Santzed. Goss not conain TSGA GBI 2H:82D5a42y5;StuRdeypeinatMeadl-eDoRsaetsDermal Tonicity --~ DuPont13830 --~ APPENDIX F PFOA ANALYTICAL REPORT ~~ -ww `CompanySanitized. Does not contain TSCACBI F2-82-5D4a2y5:StuRdeypeinatMeadl-eDoRsaetsDermal Toxicity DuPont13830 STUDYTITLE F-25425; RepeDoasetDeermdal Tox28DiaycStuidyitnMiyle Rats DRAETQAUIREMENTS Analytical Method Requiements `STUDYDIRECTOR Carol Finlay ANALPHYASTECOIMPCLETAEDLON March 10,2004 PERFORMINGLABORATORY --~ 30E5x8ygReesncaRrecsheaDrrcihve `SPtahtoenCeo:ll3e1g4e.,2P72A.110638901 `STUDYSPONSOR E.1 duPont deNemPo.0u.rBsoaxnd0Company(DuPont) Newark, DE 19714-0050USA PROIECT `SpEoxnysgoernSSttuuddyyNNou:mbeDruP:o0r0t-814308360 "TotalPages:65 Ti20-`Company Sanitized. Does not containTSCA CBI 2255-4D2a5yS;tRdeypeisntMeidl-eDoRsaetDs erma Toxicity Dupont13830 Bayi tty No:008405 ED{xe4y0ygCeSEnuRdSpaurndM1N9i2ul)mRGbao i08Lw4i0s6bc,oocurntrdeadic"fio2c5So4n2P:rR,cweohimcphpiaesnctDowneischeUnDStTEwPoxiAihOskTEySC2eC8DAPEriAnScIipCeRoEfNCGonRdI..Laborers Pacis(ts revised in 159, poled in -- PEg ixp=coRIevseesaicghtor e Boe s StyDiratord Le s Dobe DuLe.Marel Toot 5MkSseaaredens SSphoonrRepraantive LD6a-eaps-tooy BopRet Psat - wm `CompanySanli. zed. Dossnot contain TSCA CBI 2255D02a5yS: aRyepensNtieldeDRoasetsDer oxic ~ Dwron13830 `ESxtudyy Nog: 0e 08-4n06. `QUALITYASSURANCESTATEMENT cFETotn2ee5Rt1se2isv.seRQuaafolptesy dAoDseosesDeaerrUmisanTvlooixeEweed2n8B.RaensSoSnuy'dSNMuinaletbROa08sp-4nA0l6l BAiirnswernpyorPr0o 0StyDpire5 odaLparry Posi,Sts Be Lpreyies Smbmanwn oh Asalytical Repart Emre ReportReview lDouew Dubsitio DMwuBiospems SDuuDsrteiens = Peiiomeit ons oso ono oer ons ow ome ons ome ome ome ome SeOhveieier(hale Quality Assurance Auditor Beidaldad Bossa rasorss --ET GompinySaitzad. Does not contTaSiOAn Cal 1282.5D4a2y5:StRyepienatMeldeDRoasses.Dermal Toxicity Dupont13830 Eryn Sty No: 008408 CERTIFOIFCAUATHTENITIO CIN TY Thhi se pon, oorExyrenSy Nmber008406, &treandcompsrepresentationof Subminadby: x3S0u3ee8nRCoeRlceeags,hcDPhAi1v6601 Som 103 PrincipalInvestigator,Exe: Scf ns eavd esgao e Be Exp Reseach Eryn Research elyMangement: VExiycgPeanreRessleenartch Sudy Distr, Dabo: J CBiaotF oe LBbe. nar ood SporeRepresnive, DuPont: S=m. Bart BaymReach Bu(eCc insezons Peds Company Sanite zed. De ossnoe tcontaeintTSeCArGnBIo H-25425: Repeated-DoseDermal Toxicity 28-Day Study in Male Rats -- DuPont13830 ExygenStudy Nos 08-406 EIXYDGEENNSTTUIDYFICATION F-25425:Repestd-DoseDermal Tricity28-DayStyinMileRats SPONSOR STUDY NUMBER: ~~ DuPont-13630 EXYOEN STUDY NUMBER: 008-406 `TYPE OFANALYTICALPHASE: Residue SAMPLE MATRIX: Rat Plasma. TBST SUBSTANCE: Pentadecaflsorooctanccaid(PFOA) SPONSOR: EPL.L0..dBuoPxo5n0tdeNemaonduComrpasny NPheownaer:k,(3D07E) 1396761-45-2050550 ~~ STUDY DIRECTOR: CDaurPoolnFtinlay "PERFORMINGLABORATORY: ~ E3x0y5p8ReensReeasrecahrDcrhive taeCollege, PA 16801 TAONMAELTYATBILCAEL:PHASE ``SAtnuadlyyincaatlSioan DDaattee:: o1vnos:3 ``AAnnltytiiccaaTReerpmoirntaCtoiomnpDlactieo:n Dae: 0O3U/1150//0044 BayonResearch Page sof6s E Company Sanitized. Does not contain TSCA C81 H.25425: Repeated-DoseDermal Toxicity 28-Day Study in Male Rats --~ DuPont13830 BoygenStadyNo. 08-406 PROJECTPERSONNEL `fTrhoemSEtxuydgyDeinrReecsteoafrocrhwheirseparsosjoeccitaat:edDwuiPtohuvsawriaosuCsaprhoalseFsiolfsyt.h Tshteudfyo:lowingpersonnel Name Paul Connally EmilyDeckee Karen isha Mark Anmerman Shan Robb Tile TechaicalLadLMS Scientist Scents: SampleCustodien `Semple Custotion BogenResearch Pagers Tiss`Company Sanitized. Does not contain TSCA -- Cal F-25425: Repeated-Dose Dermal Toricity 28-DayStudyin MaleRats --_ DuPont-13830 ExygenStayNos 08-406 `TOAFCBONTLENETS ae GQOUOALDITLYAABSOSRUARTOARNYCPERSATCATITCEEMCOEMNPTLI.A.NC.ErScTrATeEsMsENsTeemsrc. nd. By 60 DESCOFRANIALYPTICTALIMETOHOND ---- 62PreparationofStandards4nd FOrcationSaIuions revues 11 L 65Descriptionof stunt 4dOperiingY Conions... ovr 12 ~ 7066EQXuPEaRannIdEDxMiEaSmEIpaGlNNeCatTclUAcoBcOLNncev eren r oo s m115. 9.0 ICNITEROFGTC HRETDHIU AATTATMM AYYHSAv VET AFr FEACTs EDNTHECQUAE LITYSOR 15 111000'RCETOENNTICONLOUFDSATIAOANNDSSA.MP.L.ES....m..s.vogvreossvs i1S LI OFTS ABLT ES ae TobleL SummaryofPFOA(pb)iaRa PasnaCntr Sample... 11 TeblelL. SummaryofRecoveriesof PFOA (%)inRatPlasmaSamples... 18. TableIIL SummaryofResidueFound for PFOA (ppt)inRatPlas Samples. 19 EugenResearch Puge70f65 --_ -= Company Sanitized.Does notcontTSaCAiC8n1 H2-82D5a42y5:StuRdeypeinatMeadl-eDoRsactDsermal Toxicity ~~ Dupont 13830 BeaSud No 008406 LISTOFFIGURES Be Figur1e. Typical Calbaion Curve 0PFOA verses 21 Figur2e. CWhroimatIotgaLmhRegPrCsePnFiOnRg r Clan Stam ndardfosPFOAs st 1075 2 Figu3r. C=hSrnogmmiamoLgorfamPRCe-pPrRsOeAii(nBgeyCpoennvIoD:R0a30P2a23s8CaonftorroPlFAO,ASwpiontshor ID: 69160,Se OLLAMAY osm23 Figured. PCFhvOoAmanodgr-a5mRnegp/rmesLeonfti"nCg.CPoFntOrAo(lERxaygPelnaIsDm:aF03o02t23i5Saptk1A0.pbwith Spankor ID: 669160, Set: OAM) rrr 24 Figur5e. CrSrnogmatogorfamPRCepPrFeOseAn(tEixnygRgeaaIPDa:sLaOGOSIaSmTp3l.e0f0o2r1P,FSOpAowoirtIhD: 1301, IIR renee --~ LAIPSTPOFENDICES Bae Appendix A. Study ProtocolDuPont13830(Exygen Study No. 008-406) nd AppendiBx DAneatleytmiicnaaliMoentohfodPnEtxaVdLe0ce0f8l-u2a7r6ooRteavinsciiocnA2c,i"d (MPFeOAot)fihnAnSoleryudimsboy rhe BayaReseach PasBotes EP `Company Sanitized. Does nm ot contae in TSCAn Cel 1So42y5e0s25e:SyRtayevpmrisieorhssessD0 er Toy oa wes Sy os1 10SUMMARY EEynRsst(gei) ttseeptof Apy neesn sof PFEOAki het of quanism 008-276Rev2i(AsppiendoixnB). el d 10hwhich wsc bsmeia ResiduesofPFOA ith at planasamplesrangedfrom < 100pf 134pp. h reiondv don e ROAifrr iteos mlevs 20 ommenvE Tr moctnvootftae lpn0p 58Na ooe n mohi w esi olss red 50NIBOBUCTION 1rra eofnimtpnsl ROAwin f oosetBvee tlt,toor nNmovae e1,2c0,vvie he sy5dS0c0rddi pct 40TESTSYSTEM "E R fTheconetroSlE rbate plarsma I weedfirr AcroL notorayomlsinegmpvSleesnPdpeabohrt ceBontreorlforrtifeieddsmsples `m r Seaupeloginy end cbiinofSct ustgodyinfeorsmatowiioncnavba.efouBndipnthehrawsdaapasckoage Poem rt renters eraEEsed CompanySante. Dos otoTSCA Ga H-25425: Repeated-Dose Dermal Tonicity 28-Day Study in Male e Ratse DuDupoonmt1s38l30 Exype SudyNo:008-405 50 REFERENCEMATERIAL M"aThrecshm0al5y,ic2a0l03stfarnodmarCdproitadePcaatlhoSoerrovoiicaenso.lTchceicdo(nPtFoOlAa)rtiwclser(ientecmaleastiEasnvydgaeenroddn) DpuePcoinoto.roactncic acid (1,2 dC) was eceived st Exygen on Febuary 20, 2003 from Tsthaendaavradilwibalsesionrfeordmaitnion& feofxitgheerseofreeanncdethmaetecroinatlriol lrisitecdebewlaows,stoTrheednaalyfiocoaml lepers, Compound ImmEioxreyNo. Late, PSrCPORAOA sseaesins Puity(%) EspinionDate 1 oussss Tbheeloswt.ructureofperflarooctnicacid(PFOA)and the intemalstandardsrgiven ChPeFmOicAal Nome = pefiorooctaaaccid Molecular weight = 414 Ch"ecmi_cparlONAame = perfiorooetasniodi,12:-C) Molecule weight = 416 EBxygenResearch -_-- Page 10065 Tie CompanySanitized. Does not containTSCAC81 2255.4D2a5yS:tuRdyeimpMeesRattDsder-malDTooxisciety -- Dupont13830 FargdyNeo: 00806 60 DESCORFAINALPYTITCAILMEOTHNOD 1Extracon rocdure 1. 2. Mihdehdscbnscrue0s.g1hmLse.codofdsn,cueocpeone1nt,ot1iimdgLv.iocnrpepaselnd1os0nascnecdioendg).ts0n0i0e5 (yflox.y 5. (cCnoodnov itignee gffoofro-rr 1f10osmrioe tnniesss.vaa1l4e0000a.ksxcionvolume300 pL. & AnsesumplsvingcecopryLASS. 62PreparationofSandardsand orationSolutions TCahnecsenorctkiosnudofa1n00 uyiomnobfyPFdOoAliwnsgpsrpppuorssidmoanlSye1pt0emmbegro1f7t, 2e0s5a,nadra rC{ecopoermrtoendoanolSog10preyfrihe1m7,se2t0ar0na3n,.dofcTh&oocsocimcefkaosapoanrnydof isn1eo00oanplno.f."bAyCodFirmOoiivoiwnnigs lootieiiooinnoaoffxoP"FCiO-nnAFiFsnOgtRt10weavoylraalem.epvraosp ptboyretp1aa0kr0iendgbsyLtOcirnolg.of10tmhALes.1o.if0kthsnasdlob.iconkigsfiancngsdieron _ line opto 100mlwihacne st of sands consining PFOAwithintemalsdarswspreparedbydilationof tmfhaemie10r.i.0Tphg/emelsPoFuOoAnsswoelruwateniddoth1ne o1.r0ypgt/emsLam"p'lCe-sPFnOAdtsholeuctiioan tinetdhecfaoblblorwiionng. D TCR VeR mGil) G FedCne -- 100 10 100 0.1 T2a0.5lrmibono1fA00t0iyhvL0yogpi.n"i0Co-n1PoFfO 100 A0s.o0l5utiyoanwle.sofie"dCFpFrOcA 001 imcaakcihngfl inion "aoTFhpcnma.iiTorheboeaxarndaacoesndesgarneipieroscesesdwihitogyudgahhtoewweonwxeeedok Bnaxppnrrnnoitchoensdm,etcehosnnvaclgdaoitoenc GSonye Ecc soyoedg.o 0fo0el6lo2w7nin7n g.aThh:fonicadonofte andr bore,excion 5 EE Paes --~ --- `Company Santized. Doss not contain TSCA CBI H2-52-5D4a2y5:SRtepieuantMdeadly-eDoRsaetDsermal Toxicity DuPont-13830 EsSaydyNgo.e08-4n06 "CoPFmO.A OfVFooruimfiea(llo)n VaCloummmeiof FoSroilfuitciaotnon Semple (ml) -- oor 0 oF ooot1 2500 oo1r ooii 12000 oorr CEoxtmcotefd CaSltiabnrdaatridon 30 1500 4 Tshoheueixotnacntidobnrsionlguitnigonthweavsoplruempeaurped0by10ta0kmiLngwi0.t5hmaLcroofntihse.T1h0egdi/lmuLt.io"nCsPolFutOioAn vwoalsupmreepuaprteodb10y0mtaLkiwnigt0h.S50m5L0moeftthhano1.l0wautge/rml. "C-PFOAsoutonandbringingthe i"nThaesetockistang da(r4dseol2utCiro)nawnht deanlnofotionrrset.fDiocaciuosmntaon/fedsaatrnadlnsdotilaurtbdaiporrnetspawareaittriiosonoorcnenadn. oefoundinthe awdatsasocitedwithtisreport 63Chromatography ~ "`TQhuearneitecnatiioonntiomfePoFfOPAFwOiAwsassco~mp2i0mshiend,bwyitahnnaolyssiignsiufsiicnagnetliencterfoesrpinrgapyeLaCk-sM(S</2M0S%. oftheLO standard)inthcontolsamplescorresponding ttheanalyterientontes. 64InstrumentSensittty `Thesmallest amountofPFOAinfectedduringthechromatographic onwascquivalert0 10. 65DescriptionofInstrumentand OperatingConditions sAPcEiSocniexnLdCp-rMocSeIsMsiSncgowueprleepdetcoforamHeodwulseitntgPAancaklayr:dH1.P2LsoCftswyasrte.emwaswed. Data Detailedoperatingconditionsar isedbelow: MIansersaScpee:c: SoCfotmwpaurtee:r: HPLC: PSCEISECXITEuXrAboPIIo4n0S0p0raByiLiogumidoInltrMoeadusccstiAuonnalIltyaezrefrace TDuerlbOopltoinpSlepxrOyXt1e1mp0erature =350 Cwith N2st 1Limi FPoEwSlceiesxPaAcnkaalrydst(:HVPe)rSseiroines1.12100 ExygenResearch Page 120165 BO`Company Saitized.Doesnot conTtSaCAiCBnI 425:2D5a4y25S;uRdeypienseMids-lDoRsaetsDermal Toxiity PN Dupont 13830 Egg SyNo. 008405 BHEp VqouiotouummDo.gster BHPPCAoulnuonmjneCcoomrpatment HFPiLrCCCaorlimdag:es:G2enKeesyisstConeHoynpeesrCshhe rntsondmem,tex2o1pmipanoxpm5.h0mym,4.. CNoiluenPTheamsep(,A):320mMCAmmo Aces in wale MoPhbase(i3.eleel Iw m0e wSA a3s7 vo 22550 "a0 f 55 ew" nition Vol: HL ons monitored: SB Eowaal33sin 11000 aa3s 10o0 aaass3 o 0033 ~~ CATPvORAOeA NNMeeogdgievie Top4i41o13n35M0o3n3i9tored 6QuantasdiExtamapletCaliculoatinon Fievkemaircrowlienmseofnstaemdp a 1chalalimnrstcaandvaerwdwsegeennieibyhneaeLEegMesSsIiMonS.unTrge bewctongcheinnugutoofnhoefamaolynsabtoenpceknairoenoffit)esradsaapnadkwrinagveArBSt:h 1t2i o(ofr noievliloewni)nsgeofvtasnsyn. Toricsconceniraion foPFOA wh deeming,fom Blaoqofi2|avas psedfcal0semthasamaouantdopfsesnbefoidn hpepsinfdncebasiedscsn egrsionpregneriedby h Analy sowiepagan. `EAqnautafolund(pp) =(Aas Penk eass=ecs emtx 1se. fl) XDF [---- Page 30r6s -- Company Sanitized. Doesnot contain TSCA CBI 2285.4D2ay5:SuRdeypeinatMeadl-eDoRsaetDsermal Toxicity -- ema --_-------- DuPont 13830 ExygenSoyNo:008406 wFeordstaompc lesforl itfhedpwiee tchKtnroes wconvearmyo.untsofanalyte prio(0extraction,Equation 2was REeacuosvieorny2(;9)= Analtefou"nAdm(opupnt)A.naal5y.teAanddaetd(foupn)dincone]ob) x 100 F3owrapslasemdatsoacmpalelloihedpwriethtkrneocowvnearym.os of natepir10exracton,Equation ReEcaouvmeriyo(n9"Ana0lve2 found(oph).-avz.Aneliefound sampleGpb) x 100 "AAmnaloy usddned(0tb) AIDn0e3x0a2m2p3l8eoSpfk Aa(lStla01nMuOsiAn)g,afnoartcitfuieadlsaam1p0plepfowlilohwsP:RFOaAt.pasossampleExygen = maycpekars = 21600 1SSpeeoak.a(rges/ml) =Ss41e67ng/L --~ smorpceape Gontacor ==Soao1mooedsssiss pbmafdodndeidnfcoonnmel) == N10D Fromequation 1: Asaifound(pb) = [QIGOH0U.S17I39S0I6ON=00004IS4.I1S6H7)1 = ses Fromequation2: %Reovey = 65h=1000 1050 - 0% Naoytb:TehsilsgexamdpilfefcraelnctulfartoimontwhaesvadooevseusshoiwnsfionutnhodeRdAnuWmbDerAsT,Aa.ndthecfore BopResearch Puss bot 6s Tm `Company Sanitized.Doesnot contain TSCA CBI 12.82-5D4a2y5S;tRuedpyeiantMedl-eDoRsaeDsermal Tosicty DuPont 13830 ExSadyyNoe:008n406 7.0EXPERIMENTALDESIGN coBnakscnihsostweadnclooftncarrtseratagiewotanbssl,oxko,etan5cedmsesoucmnpiclonenfgtorortloi,mweoatosodkrEneXoVowAr0yc0mo8.tn2c7x6ecRreovnoi,sli2so0nfplo2asrnid Scape,sdone fdsampleexracid idoplcte. 80RESULTS The PFOAfound ith contortplasmasamplesarlistoinTable. inndiTvaibdlaelIr.eTcohveeriaevsefroagPeFpOrAeintthosvoerrryfanodarrdoevilaatisonsfo pPFeOAcisndthte lat plasmasamwaps 97le13.s3% IRndeivsitdusalofePaFtOsAifnrtthhretPFlOaAsissnatmhpelreastepnlgansosmum<pl1e0s0probgi0ve1n3i4n5T.able IL. FAitgyupriees1lc5a.ibeaioncarvefo PFOAsdrprscottivchomsiogamsasegivenia 9.0 CIRCUTHMATSMAYTHAAVEANFFECCTE EDTSHE rm QIUALN ITYT OR EGROI FTHT E DAYTA Threaroknown circumstancstha haveaffectedtequalityofotegiyof hedia. 100CONCLUSIONS "RTehvisoitopna2.c sampleswerescssfllysledccndingfomethodExM-008.276 110 RETEOFDNATATANIDSAOMPLNES. fWosililnnbaemtsehaefthloaoil.r1eptBprhrpaiskspcceonoosmpodipre:leTotfh,sislcdooocwnndoattsp,ecpalsewdeealftlgl8oy1essoidcginbeydcrBoarpwyydaotfaRtheseuscihcnaahsl Reslepayriceeho'fsrefpcorrhteivnneds asfoulrbottrhieagpcineearlifroedlcofiyvtsiepmdecsbiycphrosvtsdpaotinasn,erw.4i0lClbFeRrPeaitn79n2t.heREexayigneedn ExygnResear Page15t6s Ee CompanySaniized. Does notconTtSaCAiCBnI H2.52-5D4a2y5:StuRdeypeinatMeadl-eDoRsaetsDermal Toxicity ~ DuPont13830 BygenStody No 08406. BoysenReseach Page 160t6S -`Company Sanitzed. Doss not contain TSCA G81 H2-82-5D4a2y5:StRuedpyeiantMeadl-eDoRsaetDsermal Toxicity DuPont-13830 ExygenStyNos 008-406 Tablel. SummoafPrFOyA (ppb)inRatPlasmaControlSamples SpoDnsor PFOA (gL) 86160Control A OTI3I0A. ND 869119ControlA 01/14/04 ND ND =NotDetcted(isthan 10.0pb) Borges Reseach Page 170065 he `Company Sanitized. Doesnotcontain TSCA C81 2285D4a2y5:SRyepnestMeadlDeoRsaetsDermal Toxicity Dupone13830 Buen SyNo:00806 Table IL. Samples Sum ofRem covea riesr ofPFy OA (%) InRatPlasma oSteTalcraoeNmroTna a vEeononeanse LCS =LiborstcyCone Spike ewHooSmrr T semun-5rTM entes MPEo&wmWs EiHi- ==-=tm -ba] Ten wr Eaten Fue tots Pe EE `Company Sanitized. Doss not contain TSCA CB H2-82.5D4a2y5:StRueypeinatMeadl-eDoRsaetDsermalToxicity -- Dupont 13830 opm Sty No: 08.405 Table IIL. Summaryof Residue Samples FoundforPFOA (ppb) In RatPlasma Spoonsor pGro)o 90w1oDrp "o10o0 o0o2 <0t000 00s4 1<i0000 s0o6r 0<1000 w0os 1<10000 1008 p1r0e0 1110082 <<110000 1110048 p<10y0 11o0r8 <110000 rr 1i1o0s8 1<10000 1110 100 1301120D0up tahs a13208 1108 11230080 111002 11530078 <uis00 1130080 n12 11551001 12s 1155002 412 11850088 1134 11880078 E1n 11560080 715124 ExygenResarh 1510. 115 Page 19065 - hm`Company Sanilized.DoesnotcontTSaCAiCBnI 2F-82-5D4a2y5:StuRdeypeinatMeadl-eDoRsaetsDermal Toxicity DuPont 13830 BasenSudyNo: 08406 BaggeReach Page200665 wm Company Sanitzed. Doss not contain TSCA CBI H2-82.5D4a2y5S;tuRdeypeinatMeadl-eDoRsaetsDermal Toxicity DuPont.13830 Eien Study Nos 008406 Figur1e. TypicalCalibCurrvaeftoriPoFOnA 8110 PRO ir agen viel 0.1708 500510 TET) | / TE ERR RRR EEAS SRR RE Aaa Fagg Research Pue21 of Ho-`Company Sanitized. Does not contain TSCA CBI 1252.5D4a2y5:SuRdeypmaaildeDoRsaetDsermal Tricity Dupont13830 Be StyNo:00406 Figur2e. ChroReprmesenatingtaCaloibragtioneStanadardmfor PFOA at10ppb with ~ 5ng/mLof "C-PFOA EST EE E= Eid BE n= Cd / va ~ =E- E=dsBe (FEE - i Boho -- Fsaztes wmCompanySantzed. Does not containTSCACBI H2.82D5a4y25S:udRyeipensMteadl-eDRoasesDena Tosiity Dupont 13830 Baya Sy No. 008405 Figure3. ChroRepmreseantintg CoontroglRartPlaasmamfor PFOAwith ~ 5 ng/moLf C-PFOA(ExygenID:0302238 EEE Control A, Sponsor ID:669160,Set: 0114044) gpos m Er Ct B= uc Bird: Eres i | | \ rn] ~~ [ra -- ET 5 Eds I | = 0 = BER EF | 3 Ese Rescue Pe otes ----- TTTTe,`Company Saritzed. Doss not contain TSCA 81 12.82-5D4a2y5:StuRdeypeinatMeld-eDoRsaetsDermal Toxicity --~ Dupont 13830 ErynSay Nos 008406 Figured. Chromatogram Represeating Control Rat Plasma Fortified 2ID:100ppb3witS0hpPk2FA,OSA2paonnd3so~rI58nDg:/66m9L1o6f0,"SCe-:PF0O11A4(0E4x4y)gen I | EE: Eisdee BE HT BEE Eu =Bee EmEr, i --~ E=TE - ER 7 -~ Eide EBOmWeEr, d i Exypen Reseach Pugs 24at65 -_e_`C_omp_any Saniized. Does notcontain TSCA CBI 2285.4D2a5y:SRteypeatMeadlDeoRastes.Dermal Toxicity Duron13830 EgeSods No: 008406 Figure. Chromatogram RepresentingRatPlasma Sample or PFOA `with ~ ng/moLf "C-PFOA(ExygenID:L0001573-0021, rem SponsorID:1301, Set: 0113048) Ee Pp =a Eide Eo E==-%m3, i EE ~~ a = EE wd. | iE ~ -- [-- Pesasares wmCompanySantized. DonotsconstinTSCA CBI 1282.5D4a2y5:StuRdeypeinatMeadl-eDoRsaetsDerm Tosicty DuPont 13830 Boren dy No: 008406 Study Protocol DuPont-13830 (Exygen Study No. 008-406) and Amendments and Deviation --~ -- Engg Reach Page260165 --wm Company Sanitized. Doesnotcontain TSCA CBI 1Z2a54y25StRy eilpeDoRseetDsermtalTeody 7~ Duns J-- | 1=ii f --_--3 H25i425:r Repesti od-Dosso Dermalr |i | I "~ |i i i| }{ titi N ero {QI | | i i Bop tas . ; i| . a! rerotss --_-- [A ---- H2-52D5a4y25S:tuRdeypienatMeadl-eDRoasesDermalToxicity --- Duponc13830 EuStgy Noe:08n-06 ; [eFrep r -- b. een ! i ~ mawsorcowans | | . ` I. 1 {! SSOanEVTAoRmTOODNUecTCnTIngeOeNnycessed i STDs | i EB E Rr ea o T n ----d -- d -- i i 8B FEBERBpetb ppr -- eo -- e -- --) -- t --" -- --~ D&FiT tS ea-- ee-- ae AS-- -- B ] -- i i | 1 A E3m mmger T m ey d ) :' STAT5OPeNB , Su e) Smee |; Raarmmos T sn--row-- s T ----------] saws, i i 1 i HE Sophos " || Pa zaots --_ -- Te `Company Sanilized. Doss not contain SOA CB ---- ~ i Somme pmom e .| q omopcmon | | pe. S------ i Thetest scbataace, K-25425,is fo. E | Ethie = | raceetc bodywe,body gHDinood crsrpton,btlbckers EEmeemmmmmER i fl we 00 gh: = ISS2Pe., Seaetiimriitsmtn | fe a.| psooommsoermmmormemeemmergmere : ~~ ! Thisstudyis spooesd byELdsPoode NewsownaadCompany,Wilisington, Delaware.The carters: | i SansEes > i LaS A rEernE mTT ! re | ERE | `Developencat(OECD),testgridelion.Aresofnoecowimllbpe dlocuriseastedaim cthe 1 somata es B1025y425,SRyephs eDoRsae Dems Toxic Ps . Duronr13sso [S---- Sm 13505.Raped DoeDecal Toiaty n3 eon : i| SeTupY spestao' u- : i | Em i woo os =a 4! { EEspas Teme-- ! | 1 BefS E iceihreEE see i B B B =B2sooEte | fot i ~~ MATEARNDIMEATHLODSS E-- ntep mei Bttir Thottmcs es Tt i | n S rieh n dpe e rm ie Tt bes ntce st aops Fr t incidence ofmentrosoas dares. i Co i ------ itedi b Bo ch reas --~ Gompiny Santzad.DosrotonlTSiOAGnE 1282-5D4a2y5:StuRdeypeinatMeld-eDoRsaesDermal Tricity -- . Dupo 13830 Ei Sly Neo:00n3406 B350aBmtnaety bowen | Crna i! frIi foomw erbR eiodd eesnhsvio 133cCoE pmedpsltorhioevyLofo0Ts4B,OAsi ii S A ter rid iy co in, Ati TCWi ti, ! | ae --_ i AnW ionbei c r abrvth e sthonustnotdr nriSmescotttotser,oogce, t! i { ++ Sei ikmrfrlbydwdfr cecrpu,s mdyitcsc.e en b : Cotes mtpe e mcT mtpe, tsos || -- ii! ren ey neiLeofn atthesecvourotmirnaoostn sbeloa wtihneimhoaaocgtoynceenyrtPoianfecdybey bheeteinssfgcyhrbre i ; I | ] in He ctr, end sp pl in. Te ; BE | ; "vi iiitt dceaty i.n ed pet weigh es of mpc i: riwiiafioby eitani n heb of odyweghes accsgn. i } BogenResch - i Pge3tofes -- To`Company Sanitzed. DossnotconTtSCaAiGBnI s 1125425n Repento Dose DermaToxic --_ . pr mstoon 1825623: Repesnd Ov DecaTaicty i Bbomperenrs " t bse F mrm--T ---- i pei aildlbiestotrePeub,lStsdtvosmgetdcatminhoteoclhockrfoor ypi sihe re. : ie eins i ET ESTR a TS I 1 ESCD ae EoRtmmEEea Eethm ti t rtt e s , ey re o ddiitres f Eachrawillbehoused 10dsignedaaanimalsuber.Prior to aesgommeatto F Sonos aE tt ErE ngamip me !i i At dy ttdy0) herswidbe weeks kd. O stdy0,whenpomswi,th i ES 5E5 ee m en ertat !,| ~ i Rat ev ct ensgt tg wh Bavabenrondo dyco - : F|[EI E e E FA . mAdmmior rfTne SiiretssBmeE e e fs ttWab yttptsaeneat,, i!; retmat rs rh pe ey em SRTAT ! i 1, EEE 2 Ta Bi | sons wizates P Company Sanitead, onwotcosta TSCA CBI H2.82-5D4a2y5:StuRdeypeinatMeadl-eDoRsatesDermal Toxicity --~ Dupont 13830 ExSyayNgose008n406 : Analia ain TY b.eesw : ii Thilbbebred be ockoemtoydGy.oTrtd ofteeeet i i! Bi r B E Souo pwillbewr gdn.Ccpoudem.ToAwwtrleyfteeienwiwlPl-- ooenprnyb-- rtanydd i i pti iii Toi mmiremyemrnyseh(moo ood yi e btntd i,nd ii | rm { BodyWeighs or ibe ged 34dotrisdog iy. i i B[ O Ervdr -- hy-- e ow-- See-- t F-- o + 1 TyCam otmomen 1 i b ClitOradMr ott Ti hSoe iao bermCreeelticciiteoo gde neon lshcwkspnt.ynTd hBsa bnrBiio . i: } i 5 To Peedeco AsLn rBro its rOr T A,T -- e d-- t e -- : | i| n efioaalt opf heftee tteefo.fTeh ondswhtpgTEhL. Tmlee i |! StRoa eRhmey Vi Katy ;} i - ) ; a. | typ Rese Pu320s65 _--_--m `CompanySanitized.Doesnot conTtSaCAiCnBI 2514-2D5u4y25S:uRd nelpDoResaesDaertToexicdity - DuPont13830 Ea SlyNo00806 [rnr m-- f. oams i f ro t an c Torkeh repi r i Se Te APCuntilmslyzadforconcentrationofperflaceooctnicacid(PFOA).Plasmaswllbe 1{ 1 R eo e beSen tenon weSad BeaReh | q KB Cl ptypaiyoBeaiitna ete m lsy beheneThne i i [: S E ee e A e e e em rS e e ereTOi lA e i {i E rr ee e EE ESTn, ] KS S t in naettym e ik tte e gd rm ii Bostm1erRiestoor tyyi coin. i! heems S Bik en 1 The ellowinghematologyparameterswillbedetained: dbloodenlloownt red el dsibutinwidth 1 i |i SEIT, ti oe pre Smite ; e tn tn e erica | emalogyBode i - BN - ; `EiygeaResearch Pa4gofe65 -- es Company Santze. Doss ot containTSGA G81 26H--2D5a4y2S5:tuRdeypienatMeadl-eDRoastesDermal Toxicity Dupont13830 pr ------ R 3508Bm ra em Tiny ies 2 ClotCoie . 1 : sTope tvingersnthseypscg wbdL int. i i ffernre S Soma EL . 1 ; So=iaim Epraeimyapropre { r- = { i 3 Urstis poheis vingwisplslhxent: : . i ii o4e HHire i pe prorte r-- Eo in ntcin Iii L Aoscoiatpasion i re i SoMis Mi Section PtFt i { 2 Dogue i1 Si nddyeosWt ltbn emtoreylyCingilor fnRoe ycewrwiple7md0 ihlrefvogrFheSihhi nviogbsievdBpelibne.dasynnef. {i i -inTecelcf Rinadevon rhet |: BL ---------- i a. i EiygenReseach Page350165 ~ Ti`CompanySanitized. DoesnotcontTSaCAiCBnI 125425; RepestDder-maDTooxisciety ESg yNa:e 008405 E ity tt Tit bi oos e ptm te toeeintderaty i i odywl cn ay 0 edbyden. T[== eme- r ; slmg= pifmeeeg=e |ii Si in | i | E chueraEtioond" e - tei- rig n km iI i Ateitheptsheppt 1 Ro eivacpnatwee iodghs ritafeveidtttebsCavdirincafctrypcsioebnioyfcoF.oSiFgmi,nooSpovetisd80 i {1 RE | -- nce fc ra mrsstbydeienaS0ywTEeSdne sowcsI ee mrg,dg ri I reais etseebiehshonr. ii{ PE r e ty eWeeenryiwr e ii SEdr tyi dy oe escsyeped | : | - . { [ES-- Pe360165 I --_-- wm Company Sanitized. Doesnot conTtSCaAiCBnI E2yA8-sD:aoy Smtudpby iinaMealergRastsS0 T --_ owes DuPont-13830 pressions smaimi s] m i stansmoALAALS i i ! - Stic wilbed <005. + er tb } I [tvyweien [= tg Freeymcno| i {i { sie" [E E [Lovoe'E sr y IpEier[erEeeeot] i - tor= EEEe == = simp i |incidenceofCtisical " i | pE----------ae mirasett i :Em Tr Sm R = i OFtihrbeomdscihlbe,ionp thy crof, mis.TTMe~ oe atid i | smS = aserovAsoe soecSieRTEPsaNGtsetstee eesr eeee :i Evie Resa PgesTores | -_-- rm - aC_om_pa--nS_tanws.wGovtoaTSCA ~ 2o50n5 RaptatsDe Toi : Pe [-- ---- ; een Desoto | mmEmmEmoETSamIREER i Al and contforsabn haractionscmd by he sponse il bosived 5 i|| E imleovfhemctsbtmnO owileecslieosae uE perpems nsd smides. aols | ! - !. i : Sse - || wf nest CompasStns, oes tataTo Zb1252y.5Ds4a2yu5S;tluyRdeyipieMnaMitadle-DRoRsaaetssDermal Toxicity PP - 0 Douwpoonwt1i38s3o0 Ba Sad y No:00m 8405 E rrm ---- b. eeen i |{ recs J RhCn iRp ria rieiy iii 5 BEGEBADATS lRGoodlNaCboeOLtLirbRtrysPioss(r0CeR,59)9,p,te dSr fyGt r,Or pei TeCoP iEoCs i fi; 5OA DpiEBA R sCapR en odR ev Sr PP" iSbeoTer si of y 7.DSW eArAd a R(2c. T , (55)ei AeldC n restect hhrd ivesiis Ti i2tsta. |{}| i 85.LeS S omano L0At5R0m )0O io3a .e7oi5ib oik mfyfnt ase,ce tGrotBtocAtbPrro.be. | -- i 1SS 0SSSeEo,RO0mNoN VemCLerU,ebR ,,00e06.51.9A6t1,nSnetiFMebstbrisonry4i630Cs i { 12ER DrknCV9L. i52W9lASEmAeL5cTptpssi ropeams ction ibisavi i}i i1 154FJ5D.AnmeT0rSAtG.e8d.uMoSi47,etEr36Hs21e, diogrkonh.PTikoem,arabi3.01B2u2r, |{ | : i a: | EpaReseach Pues ot6s -- TeCompany Sanitized. Does not contain TSCA CBI 125425: Repated-Dose Dermal Toxicity --- 28-Day Study in Male Rats : DuPont 13830 BoStgyNoe:008n-06 A5a300 brit b, re i i Pe " morocoLvrmatn i ' Ct eyB. i [S----S ! i | Aoihi in Ss Erogeea --_-- . ia To Sn sdio on Never 24,2003 f i 1 Cnetof Blood onis ere25,s2000 |i --~ i fB mi= eE) : Cotey tn f----" |! ai AuocicPatsalogyEvaiuaion. [msi December21,2003 |i | , . Ei Roars .. i a} Pus0ots --- em `CompanySanitized. Dossnot contain TSCA CBI 12.82-5D4a2y5S:tRuedypieantMedl-eDRoastesDermal Toxicity - DuPont13830 Eye StyNo:000405 rr -- Bogen7 i To sown bi eew ' i { : i i i i So ER"X='S) ; { : ; ! i i1 :: | om } T : - = _-- E-- i | : !| t " }| i Presets --~ - Te `Company Sanitized.Doesnotcontain TSCA CBI 1252-5D4ay25StRuien dMalpyDe oResaesDaermtalTeoxicdity --_ Dupont13830 ErynsdNo: 08-408 0%Rr DoeDemToy _ i | - Serres . rthPeetAnima - { I i FtDi hieprep LL. i i Torttingbt be eede mei --_ ], | matLal Ug : 1 {1 - . - - Eiygen Resarch. i} .po i Wi Page d20f65 --_-- Gompany Sanitized. Doas ot contain TSCA GBI 1250: Rens Dos Dea Toy 28-Day StudyinMale Rats ~ - DuPont 13830 peti SSiagyne jie i ett BD | i| . T Seve oo i i Enee Teptsme lo: 1. Page4,StudyDesign,mdPag 7, sectionJ. Tota FacciosdodPerfooroostaAacidc ! UD oRataionral:Trheedteyvwaoslrasiogrmmeeets. e otst rim !i --~ { mr Lbs tee oye dtrs { L. --_-- SN. --_-- .. ! } ness Company Sins, oe otconSEaAGnE H2.62-5D4a2y5:SuRdeypeinatMeadl-eDoRsaeisDermal Toxicity --~ : Dupont13830 ExygenSty Nos 008405 | Mei ; | i |i| )\ _ mGe ereg :SR ry1 tt: 0 ! i| a 1Scio ssidweno FEE EEedeyo75foog sre 0 \Ny i} |: \\ !! \ | - | remo ESD owefu |i 1 R 20 epeE e mcsTcnR fC LC oop as rewie be : !i R [CS aSdeeon"hl\e_ alE dey i| | = \| reese i oom \ : !- 5 ereot= i stl }| Xz i RE EiygenResearch Peters -- Te`Company Sanitized. Does not containTSCA CBI 22584D2a5y:SuRdeypeinatMede-DoRsaeDserma Toxicity Dupont13830 Exygen Sty Nos 008406 Analytical Method ExM-008-276, Revision 2 "Method of Analysis for the Determination of Pentadecafluorooctanoic Acid (PFOA) in Serum by LC/MS/MS" ~~ EgReseat Pugs of65 `=Comp~any Sanitized. Doss not contain TSCA CBI ZD1525yD54as2y5wSyReyMpeaatceldkeDoahstessDermal Toi ~ : oDuwrone138s30 ExygenStudy No:008406 Y { Aa : i \ ma i ! Mri hte ii } NC . mas Serr | A i Toy 04 } ~~ = i NE hr EaEesmestic ! ` JSEpiReEs, ! [r-- | -- i - mame i he =\ | Kemi i . RE i Boat . Pdbors ----------es-- `Compan-- ySanizad.-- Doesnot-- contain TS-- CA GBI BH2D:52-y5D4a2Sy5:uSuRbdeiypeiMantiMedee:DRoRssessDerma Tosisty : 00 Douwpoonwtn13s83o0 Eye Sody No: 008405 i MANAGEMENT APPROVAL i i hse te% Ett : |l gr SLyeroe | ! ~~ |ii S SE idre es [rv | | i Soest [-- . i . i on i Pe 70065 a Company Sanitized. Does not containTSCA CBI F2-82D54a2y5:StRuiendMpaeyleDeiRaRsattDseermdal Toxicity --_ Duupeomntn1s3i83o0 Era Sudy No: 008406 1 , TABLE OF CONTENTS - ! l m RO AGm ER ARYA------------ ee ---- | aIS TmORaF syI IL I I Iy T T | B5l CmHeEAnNDoM S er OU--P--R--I ---- SE | 355334.BSSoomaaommmeami me III 35 masa ores osRTOS } I53335733 a R SChrlo mammam mass raos ie t| ! owe 1 --~ ii BE -- J 5 N ----e --T u ----m ---- a ---- -- n --| Ee H 48 G m re T y | |i 5[. C7A-- LokA III ||| i |= : . = | : BE Erp Rens . res | Peas oes --~ _-- BCECompany Sanitized. Doos not contain TSCA CBI 2182D54a2y5S:udRy eMalpeDoResaetDssermtalTeoicdty Dupont13830 `ESxtudyyNog:0e 08-4n06 . i : . LisTormaLas 1 nek.vere eet | i - LiSTORFIGURES i Fm.el.hCiiirnneaSapakTHOPN CCTCnmtreyir iSseSei | Bi 5 Repose ARamis Comeangm reap fs i ey rS vFR--Oe--Nre i-- r1d | | Tn vinnie pA i i f ~~ : ! : . i - - | ops EyeRear - i . a : Pots Tas`CompanySanitized. Dos not conTtSCaAiCnB ame 1 sp et mdof kspote A PRON | i| EP= uimrosmrinad | FIOA ls cinded from sem by growin podpiaion in write, mami | Toedoefr ofquanto (LLOQfoc is sb i 103 fcFFOAls || E m me mm ma --. | | LY | | EiR -- ArepresentativecalbuationcurveforPFOAi monkeyserv ishown inFigure i - | oe Ce | $s ns - 3255D0a2y5S:aRy neepDursesDaermtalTeoxicd Duron 13530 BoaNosont ; 3 mvERMENTAL CONMPOTNDS 2 || Ths veensofpesto id(PRON)1 nerdsar se . i ii 2 PFOA it - - i! | 1 me 2c.reo CoemicalNeme row = pecfiooroacoicd,t12i-m8a-7lCo) i : | -- Bop ach --| . Pesto --------~o---- i ---- ---- -- Gompany Santzed. Does nocontain TSCACEI 1252.5Da4y2S5uRdeypeiantMealdeDoRsaesDermal Toxicity --_ Dupont 13830 ESe yNosn 008406 i a cammAesnoptPLIsES { +Gms Ce RE eReiGIaw - | || E EEmEmGeS EMhmEEe smEimleeas Gaamomeel !i 52 gramme } Breonrm dnis UetNamber Pedy rSoeawT | |i a 1 --~ ! I Prt BaypenReseach --_-- . ran i Page 20165 Company Sanitized. Doss not contain TSCA CBI H2-82-5D4a2y5:StuRdy ein MpaleDeoRsaetaDsertmaelTodri:ciy : Dupont 13830 ExyenSlyNo: 006-406 i || 23.Bayo Somas Si is mpeeme HOx T e>=ae { | Dr2aokonppeonm entcnte Gohhs.1e 0201) DramTase(4) ||| CE lpo iA pee etrsndvpoobudmoetiacfi4s55) asioTos oples | { |: | SEbeS aa ds cbastarni40,0 o= sitpg rem bin nan t i Note: Buiveent matsh ayboy subtusieodrfor tone specified hismethod ii otcrt oidonion he of pol ovei hy --_ ii 3 8 ETTaR vrFIybR eLFCkmRLImShbmsorca.tppirie,)octfm hhee,pIee VnvEeeeeondf : ) T emanm asftn orneapods bie theeddndwhe stome Ge om |i enronna evanVini- n ii | in oe in . Frps-- i 3mR mnE moeE sviR pEeogumed bfwighog i| | = "Not:Teoastiorn goenofpovieopbintstioe.i ii rote BrymResch | | Page 53065 BTSCompanySanitized.Does notcontTSaCAiCBnI iam Reiyt ar es ---- Lemma R------ :i pmmp-- --S--------, | i!i BEE S E =Ereca oetee E oAImorTncItapR semk T omtpisa4 || EEm S E E Er E r past ay | I LL pr-- i "Thesbeolatevolumesofthestander maybevaciadbytheanalystssJoogas the i| Zar recodedIntheraw das.Noto also thataddons)concentrations maybe. t| ! --~ ; SR3C S E D5.r1p.PStRocEn ksR obdons, SpeA aRdier LBaR aIlTSE EAin ||: |pD ErpeRosr pmemrI sgmet sN Troeonnecamy | : | E m EEE s i eL sa ron Gimig 10nl ofta PCFOAslaterdecid ' 3.51 10109 | |{ .2I SE ES E ES ER EI = TI erE nE !| EERE | re || Fieri nests ComplySts, Soonrteamam SCAG! 25e025s.Setop nreesDer Toy - - -- `ESxtudyyNog.: 0e08-a 406 I amtop rossis min i `SSteowaetallfo3rtiCfictaotio6n sftaonrda8cdsuolautilonsspieiosdeloifge1rysouc(f1o1n2t5h-emdLLoDeoYfE |1 { Fo prdpeation.afterwhichtineIt Jpecessacy 10makenew andasdsueng, i 353.ColaoSnare | || YE E B S=ho i tt E wtyp r yaT a sa=n econ, || wl) gob) B 8 E5 T8 = ! i 01 0 at 2 t ~~ 4. METHOD || 4B T1.FuoEwDuaIraaty raitnN E heit y| {! mesSd tSEEIE E, py !| ! | ov7is : i rtm weiI ne. n T g || -- nen || Soper ress 2285-4D2a5yS:uRdeypeiantMeadl:eDRoasteDsermal Torley --- Dupont.13830 ESe dNo:n 008406 [Lo Ee i! dbp serysh dbe ihoore ceoitoferep.c,AL ! os---- i | eschbmeooapoeexmtmsSGmeaylhCo3natos)conIme nc(aded esi | iii e aniEoTn "EoF ccbidt heoihsteppdoenrdfpbysvdy o+ yov.e : phe er hts i [rys-- i | LM 3 NiTk mfnShmatitthedeieevnoidwn.oopetneltTeioctssnstog,vs0n0e5SRlLy | 3 CE oritoee vOn mme UBCDom.me. !ii -- i 5 oun |i n451.ePSSyTeFRnSnCkEOAprtitnR B gCooo R ns m Ira. t i caper pogmsoxio | : se msnaniy2 : | | memes SDeeorbvipmaeeroirszn) | ering i i- - SETosEweo 443110cmT bypcD asosgieuet%vciuvyetibe1siK8eoyn,epurie | i pron 3 neta i EpRea : Pu 60165 ~ EY `CompanySanitized.Doesnot conTtSaCAiCBnI 12.52-5D4a2y5:SuRdy iem MapleDoResaeDsaetlToexicdity - Durant 13830 `ESx tudy y Nog:0e 084n06 : fCoisGtai GCc2m) m 0mm || IAnEetEioRnRVoTl,uSme: lS{ULaotitisse i | | S"UrawEoe RofEw8 sa smm 32 8 eu8io m |!: | - Cos Lsyoh cesa B@m 8 882= : aybesy tn HPETL pd be pic3pn | | } pCuoessm.as pe, -- PTRin) ne i| oihn JNke,m Tmospieigtmoss noeer ~~ eienn my indy dob pg o:g no a mn a | BIE [ |! Neet:eA hveLOMAS ysis bewccondeoontcd 0b || Pr . ||i SeT esmemn ElLMedn oSyn mT ybpaibtnT LiHgao. sde | [o C Fi EN he T !- a 5 433, Caltrain Procedures to m2hcisd 4 32 i Snare a `Exygen Research CL Pa57gofe65 -- CompanySaitzed. Doss not contain TSGA Gol 25525D4a2y5S: yRempleeRtaseDedrmaDlToosriei --_ : Duron13830 -- Exygen Study No.: 008-406 pr | | e froe grfiroie goorecrgi siiiodge ewomopctaAmhieLeeY | i ES rTmrme hSIIs mTERh ESE i i Thecohelationcoefficiens(1) forcalibrationcurves gesecaiedmest be. { forte de tap t orp hi o | Sandands xtheevantstofsimplesshouldbe analyz. i s Emm 04 tehws itee rsct. | 454.Sargesis i bf. Sranedsicomaponding 03 otfvo cscomccomioneels st be t! ~ || Feeesd Te a Ta 0 tes f culatesiete date int dpSpatof 4. : Ea ; Df Heeoe Snn t rrle ptynpm t t en oTtst pe me) |||| Sfeteontrieveshhoegwasl 5 118 (0 BOK clots | . I- 1. Extacidsamplescustbesored reignedbetween2C 106C mal 3 SSoEme -- in an. ;| 5Sep wichnopassmCott i.il mk ro< 1)0 Batons an | Bias } Pests ~ BunCompanySanitized.Does ot contTSaCAiGBn 12.82-5D4a2y5S:tuRdeypeinatMeld-eDoRsaetsDermal Tosicity --_ Dupont 13830 `ExygenStudy No.: 008406. ii tirppenpbuwtiapree LJesLs OthQan1the6JogweswticoncepntorrationofItheFcalibration staodards { i 4Th6eoAcacvtoemeciCaroet stichpiri"seof PFOA1 C.> i 1. Tsco oe g lovis gei i { PFFOoA:nadsaaghhtegrhlonsto3n69s37u8fromiapurepaof413 sm3u i i i 2 Aa adimmaeysaFpnobrraeL1t50bdtan mageekst56 onceeka5n ee | Ind u30nto (i coiLi0G)lofgBkcoane pAnny ii | EREIDSILIIIEE { Co re es de eb od } --_ i 4daycTiomnmooeE isstnmaoyatbct1csd1fsotlbdnbcoshnteBbyowwieen1s2 i eeomi tSdL G erot f s? s sw ek i 5. The comltion cotiio )fo cioncuesenced mtbe i i 1 20T .9925a(e72o09e05).tIfvcaibaee tiopnchesasliksfavloutstiydestthes.elusts,then i i [Er S---------- ThelTiegt-- ocstibpingdm 1r3nynsmmgybbtso || Pouca: . i 1 == TibioisndpS me od R mgceene t ows+ || i. . i vans : an i ErynReser Fuge590165 - wm Company Sanitized. Does notcontainTSCA CBI 12.82.5D4a2y5S:udRyienpMaelesRattsDeedrm-DToosisstey - Dupont13830 ExSty udyg No.:e 008-n 406. {i: i Sye xoGpootetLo0ts G0pameeo pxetSkec snrei,opiona sgs4regs ii i in ih iorccay nodrer i rc6sMon098s5. Ot | 4 ToorAvs } Fa3t meny 1raptcio.Se1 vLtes.cioTnow,LoObRAme RSpwt te,2 }! | " 5. (ucsadaLsctussLoda3m5osennpsles)willtakespprexico9uhoeulrsy. ; ia [eBritvi3e1crsliaanntsea tGo ipiper0ylbpitncdn i si pin:orm=hatsse scaco i --~ fboexecfrtiriihenooimtsyofsel cto,i EEmsSnz.- | Acts nd5 noav AAnna fsioo3ds Gg 00% i| i sary . TThEioTesehenSenaed egi,mgtionewy iiUsentmceFenopsscnicweamd i mnes agDoe tr 08 Sopmepmbaets |: ovata EopoResct --| -- i Pusceorss --_-- `CompnySanitized. Does notcontTSaCAiCnBI 1252.D5a4y2S5rRyiem alpeDoResaesDaermtalTeoidiy Dupont13830 EnStgyNoe0n8-08 i: TubeSReuceoryeyof90PkFOrA rtomePortBecattionInMeeyrSerum : | ee i | T SR EHTrEESeEE PCC | i!| =at aa=c eTeeyt | | EEEEERI: T { SEB } Sumer TOA tat ont krSm _ yr ET TY {i E--E ---- E wea TR SREER REa |i i |x : J BogenReiearch : = i rn i Pa61gofe65 -- Te GompanySanitzed. DossnotcontTSaCAiCn81 B12.D52D5ya42ys5:SwthRudMyeuMeaplrDeoReesaesDsearmtalToexicdity oDupwonte138s30 Eo ni No: 008.05 Pies.Caroncure or PFOAI Cntr MereSun i cn ror ------------------- t | qo :| { 3 3 -- ; : i 3 i ul : Ty J Bop Resecn i .| | : | : | . en}3 Pasazates -- `Company Saniized. Doesnotcontain TSCA GBI S0 12D52-5yD4a2sy5u:SyuRdeipiynenaMMtaeil-eDeoRskaetssDermal Toxiity oDuwPeonwts13s830o ; `ExygenStudy No: 008-406. i| Figure2. RSeapmrpelseefsoartiPvFCOhArowmiatt-ogmramgof ao/fCoSnlCtrPoFl.OMoAnkeySerum i {EET : = | Ei: f iJ Biic3 . | | | | : -- i bee SE | if | = | =. 3 Sovates [--. = i 1 oe. i Pssrots --_-- `Company Sanitized. Dos not contain TSCA Gall 1B25y025:Seupmsi hsDerToit ---- Sves ; Fee, BpCe hromto taT gt hSondectt t| mo "PFOAiyControlMonkey Serum with ~ 5ng/mLof "C- | 1 E= 3. + 1| EeSaE d . !! | {i| rs . -- i f Br i = | | 1 EEEEa: i | !: | || |= ' | ; omen Spr er} J -------- eetC.ompanySrites. Doesrot con7a50AiGnBI 218.25D4ay25:SuRdeypeinstMeadl-eDoRsaetsDermal Toxicity Dupont 13830 Ean Say No: 008406 i Figur4e. Representative ChromofsConttroolMognkreySaerma i FForRtiAfiedat 10ppbwithPFOAandwith ~ ng/mLofC. i i i =E=3a i | ii 1 (1h }i =F ! | F | EE | i FE | | 1- - : : : Bowntet . Expos } | i Pusat | Press --_-- \ Company Sanitized. Dossntconain TSOA GBI H2:82D5a42y5S:tuRdeypeinatMeadl-eDoRsaetsDermal Toricity DuPont 13830 APPENDIX G INDIVIDUAL BLOOD FLUORINE LEVELS -ws. Company Sanitized. Doesnotcontain TSCA C81 BH2D-82-5uD4a2Sy5:SutuRhdyeninpMMaieleeakRtaeteDsedrm-alDToorisctey INDIVIDUAL BLOOD FLUORINE LEVELS DDuuPoont m138o30 Group Dosage (mg/kg/day) "Animal Number ppb Fluorine xX 0 906 lessthan 500 x 0 907 ND xX 0 908 ND xX 0 909 ND x 0 910 ND x XI 10 1106 ND 10 1107 ND Xt 10 1108 ND XI 10 1109 ND XI 10 1110 ND Xm Xin pat Xin ~ Xi 100 1306 less than 500 100 1307 ND 100 1308 ND 100 1309 ND 100 1310 ND xv xv 1000 1506 less than 500 1000 1507 less than 500 Xv 1000 1508 less than 500 xv 1000 1509 ND xv 1000 1510 less than 500 ND = not detectable = values <200 ppb `Vales "les than 500 ppb" ae 2 200 ppb and < 500 ppb. S00 ppb = limitofquantification (LOQ) Te`Company Sanitized. Doss not contain TSCA C8I H2-82D5a42y5:StuRdeypeinatMeadl-eDoRsaetsDermal Toxicity DuPont13830 APPENDIX H INDIVIDUAL ANIMAL CLINICAL PATHOLOGY DATA Tier`sCompanySanitized. DossnotconTtSaCAiC8n. PZaLps me ------ _ Duron 3820 INDIVIDUALANIMALCLINICAL PATHOLDOAGTYA EXPLANATORY NOTES I B onDC E Ep mT mm,aegonrreste,, CottviitwouensormalE setoen vah eians, w= B SDCTmIpmI Sm o eete Oar ynheieeee, rien u CR e rne eha E MRMRm mme etE Smeeyt - BE o msE meee cn SatiiEadruEinka0eisetitecesith. srsoton vennes BpBmELCl a mm reee eh [LR0 mEive or nos xian sn whole bows sme condition odioS SnDChseeie polssceatstepiscesrrsotonyveins B m mE mma C SL oro no exami sn soi bic se coin T TnErTCp msppBeimesm lwe-- irh,, JER phGompany Sanited. Does ot contain TSCA GB! 26H--2D5a42y5S;tuRdyeinpMaeleaRattseDedrm-alDTooxisciety --~ DuPont-13830 INDIVIDUAL ANIMAL CLINICAL PATHOLODAGTYA EXPLANATORYNOTES (Continued) AmmREvIATIONS: (Continued) TadiviSdiuknl Sify C-linsiecraulm sem Chlhieeprmeoimlsiytaariys values: SAISCT AR saolseeprnauirmnteaitceatmeiarnumsoitnroatnrsafnesrtaesrease ABSIoPLH C- Satooltrkabaliltiobnlielidprheuohbsyipdnhraotgaesnease CGRBoENlA C- eCcehrooslsetsintnieitrnroeolgen TGGe gtiruisgolnyecerides Te Total protein G68 slabalin ThWiAs snoodriouamnie phosphorous EAoBH CC ELI? - Spplloaacrsnima ahleimpoolmyisaisfrofnrobnlboloododsamspalmepleforforFlufolruiodreidedetdeertmeirnmaitniaotnion ~ PFICOE C plleassmaa filcutoerriudse from blood sample for fluoride determination TndiviQduLal Urisqaulaylsiieey V(arluaedsi:os colon) ciVaoxL GVaorliutmy y Di tho logaritha of the reciprocal of the hydrogen fon concentration UKmBrbL C oubrloiononedsbilirubin WUGAFRPoO - uurrriionnbeeilpiFrnlooutgoeerniinde indivBGRiiImdTeu U-rineGepeiiMtnihecerlwoihsaicltoepcibeelllaEscxdamcienlaltsion Values: eUCRRRCY - rnmiiocnmreoeorrgceadvnaibtslamoisosd cetis SPER Cope Ti89- Company -- Sanitized.Does not -- contTaSiCnA CBI Z2DH8y-2DS5a4u2yd5:SytiuRdeoypMeinaatMleadlo-eDkoResatessDerm~al~Toxicity --~ DDuuPonot m138i30 INDIVIDUAL ANIMAL CLINICAL PATHOLOGY DATA EXPLANATORY NOTES (Continued) WOhtehneriFnadaisvoindsu,alalalntroaflwkdiaccha aacreo neoxtplarienpeordteidn, tLhte msauydyberdeuceordtso:one of the follwing reasons of tthhoVoArsLsLaEwmepsFl.eoinwntasssuticCiolcnoiiteatnetndots(ucbr1oepni)eobtfaoirnedt.est(i0ng) (QS) 2tth0hee'sasaharTmoZpeallawwdaaissedavnaopitrliaosbrulie.ttoabflsoerampTfleoesrtitcnoeglsltei(cnNtgSNi)on a Company Sanitized.Dossnotcontain TSCA CBI ~3 Ponopemue oem - IB aelEe Be 2 I meee mona Fo Be oggmsgiiied DR el3NlIE ii5 114 i ii ~ 423 Boge GResifiied FETEBRNT R zdemr aziand 2BEof sRoeeEnidT ten 8 seifsesals : 13 asemspamad Tope e33333003 v BRgd esaedvisuadcitiannd :og of ScBaRnRmEguIsEeEuRn | Sevesvesss sow1 E3EEEEEE: [ES ---- ~ 52 5 BEeSEENSE i oEREAGER 3 5 RE*EREidEd 3 *3nsdgsses 3 Be Demelainisoiannim Be eeZmEnIcaEoEnEnEe i --- i BARRE OB elEEm A Dos ome Beal oe pe sEIRNEEH i z FP 2 dJd3teidduocsieicesd Ff b U9 eBdidgiedsuEcGiEcse Ee SRININHNDefrb es33E3S3NaNeNiIaEsS 52 i 13 3 i ~ 4$33 8 E8S83 d3x3f3a3d3o3d3a3d3d {od maosnsmeny BR SRRIIGIN 2EF BEES3 eE3d3g3slsdasadEays 0 od Lseesuses & ERAN Tf sefssnunns | Sewvssesns $HEE4 ET ggesssssss IF sszsssseas Company Saniized. Donotscontsain TSCA Gal ~ : i i2 - :Dog mem q enna i Too ff mnt = ff axmny ETFl 0R ae33Y 33eY 2 ErS.2O NIEI, EON BE8} Bm3n2e.0.3anz9le8g0le7z go.p FE5X e.23o%0m30e%s09m%0m0e08s03y :z = Bp233s,aeal.5l5i%l%e,d8 = EB 3 WsIeNgIaEsEoIuIaNe FiE xCd EasQgRaEsLuGzIaCgEtS | pEd esAunnnsaanmaesn 2z 5 4b%y3 Gazi,emiaicisise.ds f p3:% oeasngdmneinasnadeds ~i @ssmsamamen 1 g3mssess [Rr ---- ~3 3 3 i f ~~ 3i 3 aSmSgBnImSeSsIsEaSn g#d e3zIa3tNaaEsEaEsEs 5 Tor EB 3ST oe Eo k3uItIIIS FE ThSNEEREY gE .23E33NIND {p Egz5%d ImasRgaEenNzaEms ogLoEaEdY epEeaMzAsaNaInsMs 4s BEE, BEEN ~3 1 ERSEEEREER GEREREREM Company Saiz. Doo acats TSCA ~8 :2 arom gan . EEE oR EE i i goer i Een Dorpgiede poli i. . 8 88 38 ' i : 58 orn Eso g 8 ifesalllsl 8 alilipl 5 ' : 2 of erm og EE 7 is ffm gE iiE Pg. ose 5F a Ee ~ 324 $ 1# agmgzmpmeasmsaanze 4 11 sgsszmzasasssaenesss Company Sanilzed. DosnotcontainTSCA Gall ~3 ii Sk Bai . Book i Pogson Bogen Bae ~~ 1i efsif 388k. Z2e8d. 0i8 $. I oep dfedb izi=cieolsol.....zo}d i Ei OF i E oe igEan He E3 HEMarlalall of$83 slEliaEbEiIiEnE zi g8 x E 8 gor i33 I: 2 ~i gE Bg os 1ammmmmmn B FR . ol Company Santized. Dooteconstin TSCA GB ~8 :2 i i BEER BE 3 8 EEE Bog 3 i oet eseff spsogEB ii Fg oocaroooem Fogg PE EEE BRE 2 LH 2 : B x BEB. 2B Erion i Cy . 14 #. gE me D B Eoin i bt ~ #i4g Foose Fae iis0 sgarssnnns 07 gJRuEaRaRaEsRsEaRsDs CompanySanitized. DoesnotconTtSaCAiCnB ~~ 3 3 i i Borgo Egon 3 BoE Bg 2. [ 3 8E 8 ExT B rEge I g 3 IOcE g R i FRE 0 FEE ERE i i H 88 gi F 2 EE s z : . a 2 BoE Faron B3 ~ 2H52L%] Bam Faso $i7g AsRmaedzamamsearnade f0g4 mzzsmsaams `CompanySaniized. DoesnotcontTSaCAiCBnI 2 5 f& 2: ~i i= Dorm ommmnn oe bomunen or ma fu HRnRD :g oF HHI 3:B H EB2 Loo sum r msin k forammeamE 10 mRBMERE Company Sand, Don otsrcAtGo ~ of i ! : iE2 RT J ee EEE oo HEE : B e nnn SRR ERT THT 13 g HEERMERREE | HEEREEEEM Br vom or aun 3 2 8g8p wReInAwYmSsSoIaRuGsR 8g8y gseRzSmIsRgRnIeAnA 8 swomsusaes fom ff sevmenenne ff nomen : 8] seamsasssn } sesaneesss Fo 48 mssssssass 5% Bp Jogsssssss : oBEuR3 5se3s3sdsssssssssss i is 3i% ~4 Toes mms om ameaanes ; g 53 sesswsssss f 5% seaesenasa o 3 SEENERA3EE BY SR33SSeE EE EH sssssesss + BREBBEEE =D BEmBpEbEE PooA nam bon opmifes nnl i foesemamszas EmEmaasEs CompanySanlzed. Does notcontain TSGA Gol ~8 i H 28 arneencuse Eg fnnanntass 8 sovenceses 89 cunausesce Eg nrnamaeess PY anozexenen ] seeamasaen gd smamaana . 8} swmemsanes 2] wavmewnens a 3 59f 2sIs3sEsIsNsEsNsEsEs oos ngdf EsmasduImEssEaEsEs _ Tops nasesanEn 2B mnmamaaEE 4 Pomme om men Sri i g 85 iiesisiee saussanass gf 43E50 ssssscanscssssseeeys :z 2 3 i ~ i23 53 s33smsfiel 3 2@%axiaisd BcesB ses E msmeAamssIsMsaIsM: EOF HBIHN 3 HHH Pog opeenneedes o@ pfmmananm i$1asmgazmzasEsmsEaRzR i 1 ssmaazmsasmsaassaes [TT ---- ~ i 8 smmosamnn Eom CR HHH Boaaminy BY ssssoaass ob nnn OE LH HH bo nmnnn i 3 zSRRaEgIaSaEzEsEsHs 3 sS3aImsaGneEss I HH i3 ~ #4 i B 2anaaaEaed oe BY dann PEE j1 u8 amman 3 Homann gy ann jor u8 mmm eo nomi et mmm a &f 8%F sAzReEzXssssazRnS Temmmmmanns ed sein | 34p % =mSswzasEsRsmzess 0 smEmBM [A ---- 35 k3y8 $s4q3ad3a3o3g33n3n8 BBEy do9m3osmgadnsaanass BORE OP oHIMEMEM POHHEHE Hmmm Pop 1 nnnnn i 3 3a%S%S3E4i3E3E7EaER 5i sAmarSeSsaimSzEaEn To.p mmm iDory mmmm :7 8833% &onAoAmdndcdedclaEn 8 onmnm orf mmm f 8 mcsemnanncanaannnme: gs 9% Issac fod moon: g ! E 2 +3 Fe 3523233238, % 23nauuaaas ik 8H8f pgeemzeeasssssazszzz [OEYBY ssynssssnnsssssazisc Company Sanitized. Does not contain TSCA GBI 2 z FERRI fr a3saoagay 3 mesgeszans BY s3ssessess 8) samsozsaas ed sudssonony CRREE f FRITHH BBall al po JPBepgpmmem TmEmRo LE a ES 8 ~ TopBEnRGbE Bppim i I sommes ew rossmsses 3 2 Pomp roa pun B i | emp, mum i FERiaziie: 2 EREferiesy ] fe pdassnudan fe 2izazzcany sencasenad BY avesewsata 8% sosozassn ed adnan sls uh yo pPammsa Pmimns Tommi ulnl a8, ow mama HEEEEEEE ~ | T ogHmEmRm opaanm 4 i | 3 222332333 = = fagnnamngn Eo TEER HEH ~ i ; 2 E [RE RTTRTER RN i F BBBeBBRERE 7 BEEREsiall : ramen : RT i 8 HEHE +E HIRE 1 HEHE Lf HEBRY Bo bs on |e sisi Corsosrteeitno ~8 3 z : 8 Tong pom = psi i HI prpmRiiEEl oz mRRBnRBLE : EB orzRrian g oapriiiiey : 8 HEHE TE2g HRI sexe FE s BBRERRNE nmninil i PRE DE NE comps, ptm H2--2D54a2y5:StRuedpyeiantMeadl-eDoRsaetsDermal Toxicity DuPont13830 APPENDIX I INDIVIDUAL ANIMAL BODY AND ORGAN WEIGHTS Es `Company Sanitized. Does not containTSCA C8l H-25425: Repeated-Dose Dermal Toxicity 28-Day Study in Male Rats INDIVIDUAL ANIMAL BODY AND ORGAN WEIGHTS EXPLANATORY NOTES Note mg/kg = mg/kg/day DuPont-13830 210Company Sanitized. Does not contain TSCA CBI ~~ 8 138! gBl 1E5! aiF qiE i ~ | EEE =a Po i |Do pnt BEaEnR Tggammamna a [oF E gimEmmEm a E Bo JR aiRi| J{ IP B la mnie se semen E5 o Bl EE Pog JiRRaadaaaa = Apm ill qka Lofagnmmnin7 iD n m h#n 1 L dEEE ee Bsfi5n3tEEzzEissen [EH|: ~=z& bo em ee CompanySn, on etc TSG ~ 8... gi i mi HE i fl ClOE Ema gi$hi{isiaisizsEaiviaisss sanl aipiT EEA EREdEEss 8i" EEE a ~ | @icoocsesess sei | fieesdecddds i 0Hpl pspIsEsEzEEaEaEgEEeRsR Maslopai isgsisneEEtzAeIumsRs RgYn pdms sp deen gE PE E| gin, sermmmesss an in, gmnEmsmnns pn jE Tai EoBl 0 1&g7 BisAsNeGaRsaAsNaEeSs aEeg)BC piieamdesndsaraoaanmigd aSsyi i Uf sanenneena3n) Fis imeneseeraeled ~H LEE EEE Company Saizad. Does notcontain TSCA GBI 2F-82-5D4a2y5:StuRdeypeinatMeadl-eDoRsaetDsermal Toxicity --~ DuPont13830 APPENDIX J INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS --~ ETNCompany Sanitized. Donote contsain TSCA CBI - BH2-D82Dy54aS2y5u:SbtRueydpyieiaMnteModaelDeRoRseaetssDermal Toxicity DDuuPoensti13s83n0 INDIVIDUAL ANIMAL GROSS AND MICROSCOPIC OBSERVATIONS EXPLANATORY NOTES Note mg/kg = mg/kg/day LesionGrading Hainsdtosepvaetrhiotlyo.giTchael cdihsatnrgiebsutairoen (deexstcernitboefdtiascscourediinnvgotlovethmeeinrtm)oirspihnodliocagtiecd,chwahreacrteera,ppdriosptrriiabuttei,obny ampopdriofpireirastes,ucishaalssofoacsasl,igmnueldtiafsocfaoll,lodwisf:fuse, unilateral, bilateral, etc.; A soverity score, if Minnoirmmaalll:imitthse.amount ofchange present barely exceeds that which is considered to be within Mild: in general, the lesion is easily identified but oflimited severity. The lesion probably does not produce any functional impairment. Moderate: the Limited tissue lesion is or organ prominent but dysfunction is there is possible. significant potential for increased severity. -- Severe: the degreeof change i either as complete as considered possible or great enough in intensity or extent to expect significant tissue or organ dysfunction. `Comment: grades minimal continuum with tmhirnoiumgahlsleevseiroensrebperiensgenttheprloegarstessseivveereinavnodlvseemveenretsleevseiroinstybaelionnggthae mthoesytaslesvoerien,dicWahtieltehetihrergelraatdievse rbeifoelrogtioctahlesmigonripfhioclanocgei.cal characteristics of lesions, Gross observations 4 etc) listing multiple masses for a tissue are distinguished with letters (i.c., a, b, , ---- me -- `Company Saniized. Does notcontainTSCA CBI H2-82D5a42y5S:tuRdyienpMaeleaRtateDsedrm-alDTooxisciety DuPont-13830 ~ Individual Animal Listing Date:20-228-013 DsorsoeoyGr|oup + I% 0 MG/KG an`AiPmPaRlOVdEaDtaPROfoTrOCOiLnd+i)vidual animals (Gontrol) Treatment: 0mg/kg IX Sex: Males Animal Ret Microscopic & Macroscopic Findings = S01 KteirlmliendalonsDaacyrif: ic2e8 Tr oT Animal is signed off from necropsy Gross pathology No MLaIcVrEoRs,copKiIDcNEAYbSn,ormTaHlYiRtOyIDOGbLsAeNrDv,edSK:IN, TREATED, SKIN, Histopathology : KvIeDNmETYNSF:LNMATION, SUBACUTE/CHRONIC, mild. CHRONIC PROGRESSIVE NEPHROPATHY, mininal. No MTiHcrYoRsOcIoDpiGLcANADb,norSKmIaNl,ityTREOAbTsEeDr,vedSKI:N, UNTREMTED s02 TKeirlmliendalonSDaacyrif+ ic28e ~~ Aninal io signed off from necropsy Gross Pathology : No MLaIcVrEoRs,copKIiDcNEAYbSn,ormTaHlYRiOtIyDOGbLsAeNrDv,edSK:IN, TREATED, SKIN, TREATED Histopathology LIvERIN: FLNGGTION, SUBACUTE/CHRONIC, mild. KIoveAYGsGR:EGATES, LYMPHOID, minimal. THYROIBD0RG0PLIACNDTMS TISSUE. No mTiHcrYoRsOcIoDpiGLcANADb,norSKmIaNl,ityTREONbTsEeDr,vedSKI:N, UNTREATED --~ ais-Compiiny Sanitized. Does not contain TSCA CBI ZH2D-82u-5DS4a2ye5S:tduRdyeypiMenaaMtaeeld-eRDRoeastessDerm~al~Toxicity DDuuPeomnit1s3l83o0 --_ n a anIinnaailvidduataal AfnoirmailndiLviisdtuianlg animals Date:20-pEa-04 sDorsoeovGr| up (+ AtProPlR)OVEDTrePaRtOmTeOnCtO:L +)0 ma/kg IX Sex: Males Animal Ret Microscopic & Macroscopic Findings 503 TKeirlmliendalonSDaacyrif: ic2e8 Cr Animal is signed off from necropsy Gross pathology : No MLOaINcVTrERoREs,cAoTpEKiIDDcNEAYbSn,ormTaHlYiRtOyIDOGbLsAeNrDv,edSK:IN, TREATED, SKIN, Histopathology xLrovweEmYTSF: LAMATION, SUBACUTE/CHRONIC, minimal. CHRONIC PROGRESSIVE NEPHROPATHY, minimal. No M`iTcHrYoRsOcIoDpiGLcANADb,norSmKIaNl,ityTREOAbTsEeDr,vedSKI:N, UNTREATED 90 TKoirlnliendalonsDaacyrif: ic28e nina is signed off from necropsy ~ Gross pathology + No MOaLNcIVTrERoREs,cAoTpEKiIDDcNEAYbSn,ormTaHlYiRtOyIDOGbLseArDv,edSK:IN, TREATED, SKIN, Histopathology LirovweEnYDSF: LA+ MKATION, SUBACUTE/CHRONIC, minimal `CHRONIC PROGRESSIVE NEPHROPATHY, minimal. No MTiHcrYoRsOcIoDpiGLcANADb,noSrKmIaNl,ityTREOAbTsEeDr,vedSKI:N, UNTREATED ~ _ 26. CompanySanitized. DoesnotcontTSaCAiCBnI H2-62-5D4a2y5S:tuRdeypieantMeadl-eDRoastesDermal Tonicity DuPont-13830 ~~ naividual Animal Listing Date:20-7z8-013 sDotsoer . +anAiemPaRlOVEdDataBROfTorOCOiLndi+)vidual animals dontzol) Treatment: ma/kg IX Sex: Males Animal Ret Microscopic i Macroscopic Findings 505 Txeirlmliendalon SaDcaryif: ic2e8 Animal io signed off from necropsy Gross pathology : No MLOaIcNVrTEoRRsE,cAoTpKEiIDDcNEAYbSn,ormTaHlYiRtOyIDOGbLsAeNrDv,edSKIN, TREATED, SKIN, Histopathology : KIDNEY`SINFLAMMATION, SUBACUTE/CHRONIC, minimal AGGREGATES, LYMPHOID, minimal. No MiTcHrYoRsOcIoDpiGLcANADo,rmSKaIlNi,tyFREONbTsEeDr,vedSKI:N, UNTREATED 30 TKeirlmliendalonsDaacyri:fic38e Animal 15 signed off from necropsy Gross pathology Yo MaLcIVrEoRs,copKiIDcNEAYmSo,maTHlYiRtOyIDOGbLsAeNrDv,edSK:IN, TREATED, SKIN, istopathology KIowEYHISENMFALTAOMPMOAITEISOINS,,SUESXATCRUATMEE/DCUHLRLOANRIYC,, ImNiCnRiEmAaSlE.D, minimal. `AGGREGATES, LYMPHOID, mininal. No M`iTcHrYoRsOcIoDpiGLcANADb,aorSKmIaNl,ityTREOAbTsEeDr,vedSKIN, UNTREATED _-- air Company Sanitized. Does not contain TSCA CBI 25H--2D5a42y5S;tuRdyienpMaeleaRattseDedrm-alDTooxiscitey DuPont-13830 ~ anIinmdailvidduaatla AfonrimiandLiviisdtuianlg animals Date:20-FEB-04 sDorsueoGylow o+"ntArBoPlR)OVEDTrePaRtOmTeOnCtO:L +)0 mg/kg It Sex: Males Animal Ret Microscopic & Macroscopic Findings TT 507 T KRielrlmeidnalonsDaacyrif:ic26e TTT Animal is signed off from necropsy Gross ratholosy No MaLcIVrEoRs,cop"KiIcDNAEbYnS,ormTaHlYRiOtIyDOGbLsAeNrDv,edSK:IN, TREATED, SKIN, TREATED Histopathology : LaverI:NPLNGGTION, THYROID GLAND. SUBACUTE/CHRONIC, minimal. HYPERTROPHY, FOLLICULAR CELL, minimal No wKiIcDrNoEsYcSo,picSKIANb,norTmREaAlTiEtDy,ObSsKIeNr,vedUNTREATED 908 TKeirlmliendalonsaDcaryif: ic2e8 Animal io signed of from necropsy ~ Gross Pathology : No MUaLNcIVTrERoREs,cAoTpEKiIDDcNEAYbSn,ormTaHlYiRtOyIDOGbLsAeNrDv,edSK:IN, TREATED, SKIN, Histopathology : LivenI:NFLAMMATION, SUBACUTE/CHRONIC, minimal KroeANsGEGC:RREOGSAITSE,S,FOLCYALM,PHOmIiDn,imamli.nimal. THYROHIYDPGELRATNRDO.PHY, FOLLICULAR CELL, minimal. No miScKIrNo,scoTpREiAcTEADo,rmSaKIlNi,tyUNTORbEsNeTrEveDd : ETCompany Sanitized.Doesnot contain TSCA C81 28H--2D5a42y5S:tuRdeypienatMeadl-eDRoastesDermal Toxicity Dupont13830 ~~ Individual Animal Listing Date:20-7Es-08s DsotsoeorGRP +an"AiPnPaRlOVdEaDta7ROfTorOCOiLndi+)vidual animals ontrol) Treatment: mg/kg IX Sex: Males Animal Ret Microscopic & Macroscopic Findings 505 TKeirlmliendalon SDaacyrif: ic2e6 - Animal io signed off from necropsy Gross pathology KIDNEDYISL:ATATION, RIGHT, PELVIS. No MaLcIVrEoRs,copTiHcYRAObInDorGmLAaNlDi,tySOKIbNs,erTvReEdNTED, SKIN, UNTREATED Histopathology LivenI:NFLATION, SUBACUTE/CHRONIC, minimal. HEMATOPOTESIS, EXTRAMEDULLARY, INCREASED, minimal `HCYHDRROONNIECBHSRROOSGTRSE,SSUINVIELANTEEPRHARLO,PATmHiYn,imamli.nisal No M`iTcHrYoRsOcIoDpiGcLANADb,norSKmIaNl,ityTREOAbTsEeDr,vedSKIN, UNTREATED - 910 mKeirlmliendalon SaDcaryif: ic2e8 Aninal io signed off from necropsy Gross athology : No MLaIcVrEoRs,coKpIiDcNEAYbSn,ormTaHlYiRtOyIDOGbLsAeWrDv,edSKIN, TREATED, SKIN, Bistopathology : LIVERIN:FLAMMNTION, SUBACUTE/CHRONIC, mild. KaoNEYACSCHGRRO:ENGIACTEPSR,OGLRYEMSPSHIOVIED,NEmPiHnRiOmPaAlT.HY, minimal 910 Continued on the next aga .... -a CompanySanitized. DoesnotconTtSaCAiCnBI ZDH2:8w2-5DS4a2yu5S;dtuRydeynpieMnaMtieadle-eDRRoaestessDermalToxicity DPDuePmonit-d1t38w30 -- . io anIinndailvidduaacla AfnoirmailndLiviisdtuianlg animals Dace:20-FzB-01 DsorseoG:roupe (o+ntAzvoelr)oveDTrepartommeoncto:r, +) mg/kg IX Sex: Males Animal Ref Microscopic & Nacroscopic Findings si Continued fron previous page o TT Histopathology Ho MiTcHrYoRsOcIoDpiGLcANADb,norSKmIaNl,ityTREOAbTsEeDr,vedSKI:N, UNTREATED -_-- m0- `Company Sanitized. Does not contain TSCA CBI 2B8DF--y2D5Sa4uy25Sd:tuyRdiyiennMpMlaeleeaRRatatsseDedrm-alDToosisciety DDuePwonlts13t83n0 sDotsoerGRP ninal Ret 1101 Gross +"aAnIPinBrdRailOvVidEduDaatlaFRAfOnoTirOmCaOilLndiL+)viisdtuianlg animals Treatment: 10 mg/kg XI Sex: Males Microscopic & Macroscopic Findings TKeirlmliendalon SDacaryif: ic26e Animal is signed off from necropsy pathology : No MLUaINcVTrERoREs,cAoTpEKiIDDcNEAYbSn,ormTaHlYRiOtIyDOGbLsAeNrDv,edSK:IN, TREATED, Date:20-FE8-04 ol oT SKIN, 1102 TKeirlmliendalonSaDcaryif: ic2e8 Animal is signed off from necropsy Gross pathology No MoaLNcIVTrERoREs,cAoTpEKiIDDcNEAYmSo,rmTaHlYiRtOyIDOGbLsAeNrDv,edSK:IN, TREATED, SKIN, 103 TKeirlmliendalonsDaacyrif: ic2e8 Animal is signed off from necropsy ' Gross zathology : No MLUaINcVTrERoREs,cAoTpEKiIDDcNEAYbSn,ormTaHlYiRtOyIDOGbLsAeNrDv,edSK:IN, TRENTED, SKIN, 108 TKeirlmliendalon SDacaryif: ic2e6 Animal is signed off from necropsy Gross Pathology : No MLTaIcRVrEEoRAs,cToEpKDIiDcNEAYmSo,rmTaHlYiRtOyIDOGbLsAeNrDv,edSK:IN, TREATED, SKIN, -------- ois ------ Compdny Sanitized. Does not contain TSCA CBI 2H8--2D54a2yS5;tuRdeypienatMeadl-eDRoastesDermalT-- oxicity DDuuPPoontm1i38s30n --_ . anIinmdailvidduaatla AfnoirmailndiLviisdtuianlg animals Date:20-rE8-04 sDroosoeyGroup +rreAaetenreonuce:n s1R0oTmooc/okLg+)XI Sex: Males Animal Ret Microscopic & Macroscopic Findings 1105 zKeirlmliendalonSDacaryif: ic2e6 Animal io signed off from necropsy Gross Pathology No MUaLNcIVTrERoREs,cAoTpEKiDIDcNEAYbSn,ormTaHlYRiOtIyDOGbLsAeNrDv,edSK:IN, TREATED, SKIN, 1208 TKeirlmliendalon SaDcaryif: ic2e8 Animal io signed off from necropsy Gross pathology : No MULaNIcVTrERoREs,AcToEpKDiIDcNEAYbSn,ormTaHlYiRtOyIDOGbLsAeNrDv,edSK:IN, TREATED, SKIN, 07 TKoirlnliendalonsDaacyri:fic28e nial is signed off from necropsy ~~ Gross pathology `DISCOLORATION, BROWN, RIGHT DORSAL LOBE. No MKaIcDrNoEsYcSo,picTHYARbOmoImDmGaLlAiNtDy,ObSsKIeNr,veTdRE:ATED, SKIN, UNTREATED Histopathology : FIBROSIS, FOCAL, CENTRILOBULAR, mild, with inflammation _-- Tm CompanySanilized. DoesnotcontainTSCAC81 BH28-l-2D5oa4y25SS:tuuRdbeyppienMatMbeadle-eDkRoaestessDermal Toricity DDo uPonmt13s830 --~ Date:20-7En-015 sroor | anIinmaailvidduaatla AfnoirmailndiLviisdtuianlg animals (+ APEROVED PROTOCOL +) Dose or Treatment: 10 mg/kg XI Sex: Males Antal Ret Microscopic & Macroscopic Findings 1108 KTielrlmiendalonSaDcaryif: ic28e TT Animal is signed off from necropsy Gross athology No MLUaINcVTrERoREs,cAoTpEKiDIDcNEAYbSn,ormTaHlYiRtOyIDOGbLsAeNrDv,edSK:IN, TREMTED, SKIN, . 1100 TKeirlmliendalonsDacaryif:ic2e8 Animal is signed of from necropsy Gross Pathology No MLaIcVrEoRs,coKpIiDcNEAYbSn,ormTaHlYiRtOyIDOGbLsAeNrDv,edSK:IN, TREATED, SKIN, mo TKeirlmliendalonsDaacyrif: ic28e Animal io signed off from necropsy ~ Gross pathology No MOaLNcIVTrERoREs,cAoTpEKiDIDcNEAYbSn,ormTaHlYRiOtIyDOGbLsAeNrDv,edSK:IN, TREATED, SKIN, _-- Ts CompanySanitized.DoesnotconTtSaCAiC8n1 H-25425: Repeated-DoseDermalToxicity 28-Day StudyinMaleRats DuPont-13830 ~~ Individual Animal Listing Date:20-FE8-0140 stoov ig+an*AiPnTaRlOVdEaDta$ROfoTrOCOiLndi+)vidual animals Dose Growp Treatment: 100 mg/kg XIII Sex: Males nial Rot Microscopic & Macroscopic Findings - B01 TKeirlmliendalonSDacaryi:fic2e8 Animal is signed off from necropsy Gross Pathology oRaL `cUaLvCEeRr/EROSION, BETWEEN UPPER INCISORS <21f DIA. No MLaIcVrEoRs,cop"KiIcDNAEbYnS,ormTaHlYRiOtIyDOGbLsAeNrDv,edSK:IN, TREATED, SKIN, 1302 TKeirlmliendalonsaDcaryi:fic2e8 Animal io signed off from necropsy Gross pathology : No MLaIcVrEoRs,copKiIDcNEAYbSn,ormTaHlYRiOtIyDOGbLsAeNrDv,edSK:IN, TREATED, SKIN, UNTREATED _ 1303 ATKenirilmmliaenldaloinssDasaciyrginfe:idc2e8off from necropsy Gross Pathology : No MLaIcVrEoRs,coKpIiDcNEAYbSn,ormTaHlYiRtOyIDOGbLsAeNrDv,edSKIN, ONTREATED TREATED, SKIN, 1308 mKeirlmliendalonsaDcaryi:fic2e8 Animal is signed off from necropsy Gross Pathology No MLTaIcRVrEEoRAs,cToE"pDKiIcDNAEbYSn,ormTaHlYiRtOyIDOGbLsAeNrDv,edSK:IN, TREATED, SKIN, -- CompanySanitized. Doesnotcontain TSCA Cal ZDH2--u2D5Sa4y2u5dS:tvuRdeiypioenaMMtaeldle-eDRRoasetessDermal Toxicity DDeuPmonti138n30 --_ n uty anIinmdailvidduaatla AfnoirmailndLiviisdtuianlg animals Date:20-7E8-04 sDotseoGr| oUPM + APTPreRaOtVmEeDnt:PROT1O0C0OLmg+)/kg XIII Sex: Males Animal Ret Microscopic & Macroscopic Findings 1308 KTeirlmliendalonsaDcaryif: ic2e8 - Aninal ic signed off from necropsy Gross Pathology : No MLUaINcVTrERoREs,cAoTpE"KiDIcDNAEbYSn,ormTaHlYiRtOyIDOGbLsAeNrDv,edSK:IN, TREATED, SKIN, 1306 Keirlnliendalon sDaacyrif: i3c8e Animal is signed off from necropsy Gross pathology : No MLTaIcRVrEEoRAs,cToEp"DKiIcDNAEbYSn,ormTaHlYiRtOyIDOGbLsAeNrDv,edSK:IN, TREATED, SKIN, 107 KTielrlmiendalonSDaacyrif: ic28e Animal io signed o from necropsy ~~ Gross Bathology No MaLcIVrEoRs,copKiIDcNEAYoS,maTlHiYRtOyIDOGbLsAeNrDv,edSK:IN, TREATED, SKIN, 1308 TKeirlmliendalonsDacaryif: ic2e8 nial is signed off from neczopsy Gross Pathology : No MaLcIVrEoRs,copKiIDcNEAYbSn,ormTaHlYiRtOyIDOGbLsAeNrDv,edSKIN, ONTREATED TREATED, SKIN, _--_--nm `CompanySanitized. Doesnotcontain TSCAG81 282HD-82o-5Dy4aS2y5wS:dtuyRdiyeninMpMaaelleaoRRtaatessDedrm-alDTooriscitey DDuuoPmonits1s3l83o0 ~~ Individual Animal Listing Date:20-7E8-0142 sroov | an"AiPmPaRlOVEdDa.taPROfoTrOCOiLnd+i)vidual animals Dose orp ? 5 Treatment: 100 ng/kg XIII Sex: Males Animal Ret Microscopic i Macroscopic Findings 1305 KTeirlmliendalonSDaacyrif: ic26e Animal is signed off from necropsy Gross pathology : No MLaIcVrEoRs,copKiIDcNEAYbSn,orTmHaYlRiOtIyDOGbLsAeNrDv,edSK:IN, TRENTED, SKIN, 1310 KTielrlmeidnalonSDaacyrif: ic2e8 Animal is signed off from necropsy Gross ratholoay No MOLaNIcVTrERoREs,AcToEpKIDiDcNEAYbSn,ormTaHlYiRtOyIDOGbLsAeNrDv,edSK:IN, TREATED, SKIN, --_~ _--m Tee Company Sanitized. Doesnotcontain TSCA Cal 28H-:2D5a4y25S;tuRdeypienaMtaedl-eDRoastesDermal Toricity DuPont 13830 ~~ Individual Animal Listing Date:20-rER-0113 DsotseuGLE +"aAnTriPenBaaRtlOmVeEdnDatc:aPROfT1o0Or0C0OiLnmda1i/vkigdusWlV animals Sex: Males Aninal Ret Microscopic i Macroscopic Findings 501 TKeirlmliendalonSDaacyrif: ic28e Animal is signed off from necropsy Gross Pathology No MOLaNIcVTrERoREs,AcToEpKDiIDcNEAYbSn,ormTaHlYRiOtIyDOGbLsAeNrDv,edSK:IN, TREATED, SKIN, Histopathology : L1veRTNFLNGATION, SUBACUTE/CHRONIC, mild. No MKiIcDrNoEsYcSo,picTHAYRmOoImDmaGlLiAtNDy,ObSsKIeNr,vedTRE:ATED, SKIN, INTRENTED 1502 TKeirlmliendalonsDaacyrif: ic2e8 Animal io signed off from necropsy Grose pathology ~ No MLTaIcRVrEEoRAs,cToEpKDiIDcNEAYbSn,orTmHaYlRiOtIyDOGbLsAeNrDv,edSK:IN, TREATED, SKIN, Histopathology LrvemINFLATION, SUBACUTE/CHRONIC, minimal No MKiIcDrNoEsYcSo,picTHAYbRnOoIrDmaGlLAiNtDy,ObSsKIeNr,vedTRE:ATED, SKIN, UNTREATED 1503 TKeirlmliendalonsDaacyrif: ic3e Animal is signed off from necropsy Gross Pathology : No OLMNIaVTcERrREo,AsTcEoRpDIDiNcEVASb,norTmHaYlRiOtIyD OGLbAsNeDr,vedSKI:N, TREATED, SKIN, -_-- mre Company Sanitized. Doss not contain TSCA CBI Z28DH--2uD5a4S2y5S:utubRdeypibenaMMtaeedl-eDRkoastsesDermal Toxicity DDuuPonot-1m383o0 ~ Inaividual Animal Listing Date:20-PEB-0140 sDtooseyGroup + HY. (-a*nAivmearlovdeantsarofroorcoirndi+)vidusl animals Treatment: 1000 mg/kg XV Sex: Males Animal Rot Microscopic i Macroscopic Findings 1503 Continued from previous page Histopathology : LaveI:NPLNGATION, owes SUBACUTE/CHRONIC, minimal. THYROICADGHGRRGOELNGAIANCTDEPSR:,OGLRYEMSPSHIOVIED,NEmPiHnRiOmPaAlT.HY, minimal `HYPERTROPHY, FOLLICULAR CELL, minimal. No MSiKcIrNo,scoTpREiAcTEADb,norSKmIaNl,ityUNOTbRsEeNrTvEeDd 1502 KTielrlmeidnalon SDaacyrif: ic38e nial is signed off from necropsy Gross Pathology : --~ No MLOaINcVTrERoREs,cAoT"pEKiDIcDNAEbYSn,ormTaHlYiRtOyIDoGbLsAeNrDv,edSK:IN, TREATED, SKIN, Histopathology : LiveTN; FLAMATION, SUBACUTE/CHRONIC, mild. No MiKcIDrNoEsYcSo,picTHAYbRnOoIrDmGaLlAiNtDy,OSbKsIeNr,vedTRE:ATED, SKIN, UNTREATED 1505 KTielrlmeidnaolnSDaacyri:fic28e Animal is signed off from necropsy Gross pathology : No MLUaNIcTVrREoERsA,cToEKpDIi.DcNEAYbSn,ormTaHlYRiOtIyDOGbLsAeNrDv,edSK:IN, TREATED, SKIN, 1505 Continued on the next page... -_-- Tm `CompanySanitized. Dosnot contain TSCACBI ZD0 H2-8w2-5SD4a2uy5:bStyuRdiyeMinpiMaeeleRaRetatseDsedrm-alDTooriscitey DDuupoonmt1u38s3n0 anIinmdailviddautael AfnoirmailndLiviisdtuianlg animals Date:20-7E8-04 Dsorsoeoy " +" ATrPePaRtOmVeEnDt:PROT10O0C0OLng+/)kg XV Sex: Males Animal Ret Microscopic i Macroscopic Findings 50s Continued from previous page Histopathology : LivenTNFLNGIATION, SUBACUTE/CHRONIC, minimal. No MiKcIDrNoEsYcSo,picTHAYbRnOoIrDmaGlLAiNtDy,ObSsKIeNr,vedTREATED, SKIN, UNTREATED 1506 TKeirlmliendalonsDaacyrif: ic2e8 Animal {s signed off from necropsy Gross Pathology No MLNaIcTVrREoERsA,cToE"pDKiIcDNAEbYSn,ormTaHlYiRtOyIDOGbLsAeNrDv,edSK:IN, TREATED, SKIN, Histopathology . --~ venINPLAGTION, SUBACUTE/CHRONIC, minimal. Ho MiKcIrDNoEsYcSo,picTHYARbOnIoDrmGaLlAiNtDy, OSbKsIeNr,vedTRE:ATED, SKIN, UNTREATED 1507 TKAneiirlmmlaielndaloinsssDaicagrynief:dic2e8off from necropsy Gross zathology : No MLUaIcNVrTEoRRsE,cAoTp"EKiDIcDNAEbYSn,orsTaHlYiRtOyIDOGbLsAeNrDv,edSKIN, TREATED, SKIN, Histopathology 1507 ContinuedLoanvetrhI;eNFnLexAtTIpOagNe, -.SUBACUTE/CHRONIC, minimal -- -_-- -CompanySanitized. Dossnotcontain TSCA C81 28H--2D5a42y5S; tRdienpMaeleaRRatetseDedrm-alDTooriscitey DDuuPPoontm1n38g30 ~ Individual Animal Listing Date:20-rz8-0146 DsotsoerGibup i(o+anAipnEaRlovEdDataProfmoorcoiL.ndi+)vidual animals Treatment: 1000 mg/kg XV Sex: Males Animal Rot Microscopic & Macroscopic Findings 1507 Continued from previous page Histopathology + mxeavnR,OHIYODPNERGRELTAARTNOEDPDH.Y, FOLLICULAR CELL, minimal INPLAMTION, FOCAL, SUBACUTE/CHRONIC, minimal, dermal. No MKiIcDrNoEsYcSo,picSKIANb,norTmRaElAiTtEyD Observed 1508 TKAneiirlmmlaielndaloisnssDaaicygrnief:dic28oeff from necropsy ross pathology : No MLUaINcVTrERoREs,cAoTpE"KiDIcDNAEbYSn,ormTaHlYiRtOyIDOGbLsAeNrDv,edSK:IN, TREATED, SKIN, Histopathology : ~ KLIrDvNeEmYISNF+ LATION, SUBMCUTE/CHRONIC, mild. `CHRONIC PROGRESSIVE NEPHROPATHY, minimal. No MTiHcrYoRsOcIoDpGiLcANADb,norSKmIaNl,itTyREOAbTsEeDr,vedSKI:N, UNTREATED 1509 TKeirlmliendalon sDaacyrif: ic2e8 Animal is signed off from necropsy Gross rathology No MOaLNcIVTrERoREs,cAoTpEKiDIDcNEAYmSo,rmTaHlYiRtOyIDOGbLsAeNrDv,edSK:IN, TREATED, SKIN, 1509 Continued on the next page .... -_-- 230`CompanySanitized. Doesnot contTSaCAiCnBI H2-82-5D4a2y5S:tuRdeypienatMeadl-eDRoastesDermal Toricity De DuPomnt1s 3830 --~ ww stovy "aAnIPinPmdRaiOlvViEddDauatlaPROAfTnoOirCmOaiLl,ndLi+)ivsidtuianlg animals Date:20-783-04 Dose GratET Treatment: 1000 mg/kg XV Sex: Males Animal Ret Microscopic & Macroscopic Findings "- 1505 Continued from previous page - oT Histopathology : LivenNI.ENCFRLOMSGIAST,IOFNO,ALS,UBAmiCnUiTmEa/lC.HRONIC, minimal. SKIN, IUNNPTLRAEGAITTEIDON, FOCAL, SUBACUTE/CHRONIC, minimal, muscular. No MKiIcDrNoEsYcSo,picTHAYbRnOoTrDmaGlLAiNtDy,ObSsKIeNr,vedTREATED 1510 KTielrlmeidnalonsDaacyrif: ic28e Aninal is signed off from necropsy Gross Pathology : No MUaLNcIVTrERoREs,cAoTpEKiDIcDNAYbSn,ormTaHlYiRtOyIDOGbLsAeNrDv,edSK:IN, TREATED, SKIN, Hissttopoapthaotlohgoylogy : LKIiovweErYIsNFLRBATION, SUBACUTE/CHRONIC, mild. SKIN,CHTRROENAITCEDPR+ OGRESSIVE NEPHROPATHY, minimal. INFLAMIATION, OCAL, ACUTE, minimal, epidermal. Mo M`iTcHrYoRsOcIoDpGiLcANADb,norSKmIaNl,ityUNTORbEsNeTrEvDed : "++ Listing complete wer --_ TT -- `Company Sanitized. Does notcontainTSCA CBI