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|| AR226 3232 DuPont TRADE SECRET Study Title H-24768: Developmental Toxicity Study in Rats Laboratory Project ID: DuPont-6515 "TEST GUIDELINES: U.S. EPA Health Effects Test Guidelines OPPTS 870.3700 Prenatal Developmental Toxicity Study -- (OECD Guidelines for the Testing of Chemicals Section 4, No. 414 AUTHOR: Susan M. Munley, M.A. STUDY COMPLETED ON: February 25, 2002 PERFORMING LABORATORY: E.L du Pont de Nemours and Company Haskell Laboratory for Toxicology and Industrial Medicine Elkton Road, P.O. Box 50 Newark, Delaware 19714-0050 Page 1 of 165 Company Sanitized. Does not contain TSCA CBI 1.24768: Developmental Toxicity Study in Rats DuPont6515 GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT `This study was conducted in compliance with U.S. EPA TSCA (40 CFRpart 792) Good Laboratory Practice Standards, which are consistent with the OECD Principles of Good Laboratory Practice (as revised in 1997) published in ENV/MC/CHEM(98)17, except for the item documented below. The item listed does not impact the validityofthe study. The bulk test substance characterization and stability analyses were performed at DuPont Regional Analytical Services (RAS)a, non-GLP laboratory. These analyses were in compliance with regulatory guidelines. Noneofthe aforementioned analyses were performed under Good Laboratory Practice Standards; however, the analyses were conducted in compliance with ISO9002 regulations. Allof the analyses are considered valid and sufficient for the purposesofthis study. Applicant SponsorWi.1l.midnugloonn,dDeelNawaerem19a8on9d8Cuomrpansy. USA. - `Study Director: honoM Mu unlery. d5-Foemb e50032 Reseach Scientist Appican/ Sponsor:TDTwenRepemae Dw --- Company Sanitized. Doss not contain TSCA CBI H24768: Development] Toxicity Study in Rats QUALITY ASSURANCE STATEMENT Haskell Sample Number(s): 24768 DatesofInspections: Protocol: May 1,2001, Jan. 14,2002 Conduct: May 4,9, 2001, July 11,19, 2001 Records, Reports: Jan. 15-18, 21-282,2400,2 Dates Findings Reported to: Study Director: Jan. 28,29, 2002 Management: Jan. 28, 2002, Feb. 20, 2002 Duponcests Reportedby: C Faber C. CR QultyAsan Audie 25 [FDeabe Yoon _-- Company Sanitized. Does not contain TSCA CBI 24768 Developmen Toiy Sy nas Dupons1s CERTIFICATION `fWreo,mtthheisunsdteurdys.igned, declare that this report provides an accurate evaluationofdata obtained CaDeol nrda aotpeeds ABT Tsp saahna es ns mattyrSetayds nos ee aon 5Rfo eb _-- Company Saiized Doss no cori vacon 124768: DevelopmentalToxicity Study in Rats Dupont6s15 TABLE OF CONTENTS Page GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT ..ccvcsrrnd QUALITY ASSURANCE STATEMENT worsened CERTIFICATION cvs STUDY INFORMATION sss] STUDY PERSONNEL vcesosssmsssmssmssssssmsssmssssssssssssssssssmmrsonon SUMMARY corms OBJECTIVE coves 0 MATERIALS AND METHODS v.ccorvrsnssssssssssssmssssossnsenssnronssnnel0 A. Test Guidelines smmm------------_0 a --" ~ D. TAniImaRlEHuDsbanp dry... u rsm ---- m ---- e ---- l -- 2L. FHousuienndg Weaterd... ASI CIInr} 43. HMedeatlitihcMaotinoint.o..r.ing Program.ors CII CII In E. QUATBNne and Pretest PEriOd......vvrvevrvrvrrrnemsrsmsremrermsmsmsosossosmsen 12. J G. SCloOcFDOtSEiLEoVELnS. s--------lb rere 2 3 IA . Preparation, Administration,andAnalysisofTest SUSPENSIONS .......v.orvrnrrervrnee||3 K. P1. IAnifeAO1bI0sbe6ISrvOaCCotf.FiE.eom.inlTss. S cg BT13 23.. PFoesttumsosrtofeFmeOmbasleersvaStuirovnisvoinfgF1e0mSaclheesduSluervdivEiUnghfaonaSscaheduled ..... Ewhanasa..... TsIH L. CONMIOLOFBil. M.Statistical ADalyses........... cesnimm-- A ems RESULTS AND DISCUSSION cssssssmssssmsssssssssssssssosnsssinsnosnnel A. M1 ateMmoarlaFlindings em-- em---- ---- CI t16 32.. BBooddyyWWeeiigghhts.h.i.nges. . SI CII SE Te16 - 4 FoodConsumption... LI nt -_-- Company Sanitized. Doss nol contain TSCA CBI H-24768: DeveloToxpicimtyeStnudytinaRalts DuPont6515 - 5. ClinicalObservations. 6. PostmortemFindings ss---- em-------- wns]7 FR 1. Moraliy..... ------ ned] F3.I MalformatioCnsS...... ---- nm------------------ ------------_5 4. Variations smtm-------- 18 CONCLUSIONS ocr 19 RECORDS AND SAMPLE STORAGE cms19 REFERENCESsss20 TABLES wns Zl TABLE | MEAN MATERNALBODYWEIGHTS smm----------_t `TABLE 2MEANMATERNAL BODYWEIGHT CHANGES. smmmmsnnddl TABLE 3MEANMATERNAL FOODCONSUMPTION... 21 TABLE CLINICAL OBSERVATIONS cc... sms) TABLE REPRODUCTIVE OUTCOME ccs: 30 `TABLE 6INCIDENCE OFFETALMALFORMATIONS. sms] TABLE 7INCOIFFDETAELVANRIACTIOENS cvs " wilh - APPENDICES cco 36 APPENDIX A INDIVIDUAL BODY WEIGHTS. 3 APPENDIX BINDIVIDUAL BODYWEIGHT CHANGES cn S| APPENDIX CINDIVIDUALFOOD CONSUMPTION. s---- 61 APPENDIX D INDIVIDUAL CLINICALOBSERVATIONS... smmmmndl) APPENDIX E GROSS POSTMORTEMFINDINGS snm----. APPENDIX FINDIVIDUAL REPRODUCTIVEDATA ........ e100 APPENDIX GINDIVIDUALFETAL WEIGHTSAND ALTERATIONS. . 106 APPHAENALN YTICDAL RIEPOX RT... 154 -_-- `Company Sanitized. Does not cniain TSCA C81 H24768Developmen Touhy SudyioRas__ STUDY INFORMATION puwomssis + H-24768 Haskell Number: 24768 Physical Characteristics: Tan to light brown paste Stability: The test substance appeared to be stable under the conditionsof the study; no evidence of instability was observed. Sponsor: WE.ilI.midnugPtoonnt, dDeelNaewmaoruer1s9a8n9d8 Company USA Study Initiated/Completed: May 4, 2001 / (sce report cover page) - In-Life Initiated/Completed: May 6, 2001 / August 23, 2001 ------ iee-- e ------------ Company Sanitized. Does not contain Ts04 cay H-24768: Developmental Toricity Sudy in Rats STUDY PERSONNEL Study Director: Susan M. Munley, MA. Management: Robert M. Parker, Ph.D, D.A.B.T. Primary Technician: Kellie Mellhatton Toxicology Report Preparation: MaryK. LaRoe Laboratory Veterinarian: William Singleton, D.V.M., A. CLAM. DuPont6515 - Company Sanilized. Does not contain TSCA CBI H.24768: Developmental Toicity Study in Rats DuPont6515 SUMMARY Groupsof 22 female Crl:CD(SD)IGS BR time-mated rats were administered suspensions of H-24768 in water once daily by gavage over days 6-20 ofgestation (G) at dose levelsof0, 50, 100,or 400 mg/kg/day. During the dosing period, body weight, food consumption, and clinical observationdatawere collected daily. On day 21G, all dams were euthanized and examined for gross external and visceral alterations. The uteri were removed, weighed, and dissected. The uterine contents were examined; the fetuses were removed and weighed, sexed, and examined for external, visceral, head, and skeletal alterations. Maternal toxicity was evident at 100 and 400 mg/kg/dasy significant reductions in maternal body weight, weight change, and food consumption. The magnitudeofthe quantitative maternal changes at 400 mg/kg/day was marked. Increased clinical signsoftoxicity accompanied the weight and food consumption reductions at 400 mg/kg/day. There were compound-related effects on maternal weight, weight change, and food consumption at 50 mg/kg/day but these changes were generally minimal and transient and as such, were not considered adverse. Developmental toxicity was evident only at 400 mg/kg/day as significantly reduced mean fetal `weight and increased fetal variations (delayed skull bone ossification and increased supernumerary ribs). There was no evidenceofdevelopmental toxicity at 50 or 100 mg/kg/day. `There were no compound-related fetal malformations at any level tested. Under the conditionsofthis study, matemal toxicity evident as reduced body weight and food consumption was observed at 2 100 mg/kg/day. Non-adverse changes in dams occurred at 50 mg/kg/day and thus, the maternal no-observed-effect level (NOEL)A was considered 50 mg/kg/day. Developmental toxicity was evident at 400 mg/kg/day as reduced fetal weight and increased fetal variations. The NOEL for developmental toxicity was considered 100 mg/kg/day. - aTwnehdree0NnOotthEedLeot-feocotbrestdei.rsvTsehtduuasdd,yvfieosrdsetefh-iiesnfesedtacudty,ltehtveehlehi(NgNhOeOEsAtLEdLioss)ceaqasitdvweahfliincntehdfaobdyvtehtrehseNe EOeuEfrfLoept5es5asndtUernfiibinuoetdnabb(ly1e9tt9h4e)t.hUe.S.tesEt PsuAbs(i1a0n8c5e) eee ee ~esmme---- Company Sanilized. Does not cantain TSCA CBI H2H-42747668%:DeDveevellooppmmentalTTooxxiicciitty SStuuddyyiinnRRattss _ DDuuPpoonm6s5i15s OBJECTIVE The purpose of H-24768 in rats. this study was to evaluate the potential maternal and developmental toxicity of MATERIALS AND METHODS A. Test Guidelines The study design complies with following est guidelines: + TUonxiitcedSSutbastteasnEcnevsi(rOoPnmPeTnSt)alHeParlotthecEtfifoenctAsgTeensctyG(uEiPdeAl)i,neOsf,fiOcPePoTfSPr8ev7e0n.t3i7o0n,0 PPersetniactiadles, and Developmental Toxicity Study (1998). + OCrhgeamniicsaaltsi,onSefcotriEonco4n(oNmoi.c4C1o4)o.pePraartii,onFraanndceDe(v19e8l1o)p.ment. Guidelines for Testing of --- B. Test Substance HE.-2I.4D76u8PwonatsdseuNpepmloiuberyds tahnedsCpoonmspoarn,yt,heNDeuwaProkn,t CDehleamwiacrael.SoHl-u2t4i7o6ns8 Einstaerppasrties.e (IDt CwSaEs), achsasriagcnteedriHzaastkieolnlaLnadbsotraabtiolirtyyoNfutmhbeetres2t4s7u6b8s.taTnchee. sTpeosntsosrubwsatsanrceespaonnasliybsleesfwoerrteheconducted by rDeusPeorvnetsRaemgpiloenoafltAhnealtyetsitcsaulbSsetravnicceeswa(sRAcSo)ll,eJctaecdksaonnd Lraebtoarianteodrbieys,DuDPeoenptwaHtaesrk,elNleLwabJoerrasteoyr.y.A C. Test Species `The Crl:CD(SD)IGS BR rat was selected for this study because it developmental toxicity testing as recommended by the guidelines. is a The preferred species for Crl:CD(SD)IGS BR ssturpapilniewra,sancdhopsreenviboeucsasutsuedieexstewnistihveotbhaecrkcgormopunodunidnsfoartmaHtaisoknelils aLvaabiolraabtloeryf.roTmhtihsestlirtaeirnatiusrae,lstohe considered suitable relative to hardiness and incidence of spontaneous disease. re Lompany Sanitized. Doesnot contain sca cel H24768: Developmental Toxicity Study in Rats DuPont 6515 - Eighty-cight nulliparous, time-mated females, were received on May 3, 2001 (66 females) and May 4, 2001 (22 females) from Charles River Laboratories, Inc., Raleigh, North Carolina. Body weights on the day the rats were mated, day 0 ofgestation (day 0G), were supplied by the vendor. The rats for this study were at cither 1, 2, or3 daysofgestation upon arrival. D. Animal Husbandry 1 Housing Animal rooms were maintained at an acceptable temperatureof 20-26C (targeted at 23C) and a targeted relative humidityof 50% = 10%. Animal rooms were artificially illuminated (fluorescent light) on a 12-hour light/dark cycle (approximately 0600-1800 hours). Animals were housed individually in suspended, wire-mesh, stainless steel cages. Nesting material was not provided because the dams were euthanized prior to parturition. 2. Feed and Water PMI Nutrition Intemational, Inc. Certified Rodent LabDiet 5002 (formerly known as Purina CertifiedRodent" Chow) was available ad libitum. available ad libitum. Water from the United Water Delaware was 3. Identification - bEyacthheasnuipmpalliewrapsriaosrstiognsehdipapuinngi.quUepnounmbreecreiapnt,d ewaacsh iadneinmtiafliewdawsiatshsaingnAedVIaDunMiiqcureoHcahsikpelilmplant animal number. Both the Haskell animal number and the AVID Microchip implant number or ctaoirlrmeasrpkonwdeirneg urneicqorudeeAdVoInDeaMcihccraogcehicparidm.plAanmtansutmerbelirsst oisfmuaniinqtuaeinHaesdkweiltlhatnhiemasltunduymrbeecorrsdsa.nd 4. Health Monitoring Program `As specified in the Haskell Laboratory animal health and environmental monitoring program, the tfhoolsleowtihnatg wprooucleddubreeesxapreecpteerdftoorimmepdapcetritohdeicscailelnytitfoicenisnutregeritthyaotfctohnetasmtiundayn:t levels arc below + Water samples are analyzed and other contaminants. for total bacterial counts, and the presenceofcoliforms, lead, + Feed samples are analyzed for total bacterial, spore and fungal counts. + Samples from freshly by the cagewashers. washed cagesand cage racks are analyzed to ensure adequate sanitation Certified animal feed is used, guaranteedbythe manufacturer to meet specified nutritional - rspeeqcuiifrieemdehnetsavayndmentoatlst,oaefxlcateoexdins,tactheldormianaxtiemd uhymdrcoonccaernbtornast,ioannsdoofrgkaenyocpohnotsapmhiantaenst.s,Tihnecluding - ah `Company Sanitized. Does not contain Tera Aa) 1.24768; Developmental Toxicity Sudy in Rats DuPont6515 - presenceofthese contaminants below the maximum concentration stated by the manufacturer `would not be expected to impact the integrityofthe study. Tlahbeoraantiomraylahneiamlatlh vaentdereinnavriiraonnmEevnatlaulatmioonniotfotrhiengseprdoagtaradmidisnoatdmiinndiisctateereadnybycotnhdeiattitoennsdithnagt affected the validity ofthe study. E. Quarantine and Pretest Period Rats were quarantined according to procedures outlined in Haskell Laboratory SOP LA0O3-P, and then released for the study upon approvalofthe Laboratory Animal Veterinarian designee. F. Study Design The experimental design is shown below: Suspension Group Dose* (mg/kg/day) Concentration| Time-Mated (mg/mL) Females - 1 0b 0 2 [ 50 5 m 100 10 2 2 nv 400 4 2 a Hvo2l4u7m6e8o,fa1d0mimniLst.ered by oal gavage, on days 6.20ofgestation (G), ata dose > Vehicle (deionized water) G. Selection of Dose Levels `The dose levels for the current study were based on results oaf rat pilot developmental toxicity `study with the test substance." For the pilot study, groups of8 time-mated female Cgarvia:gCeDoYvSeDr)dIaGysS 6B-R20raotfsgweestraetiaodnmi(nGi)stater0e,d5s0,us1p0e0n,si4o0n0s,oafntdhe70t0esmtgs/ukbgs/tdaanyc.e once daily by Maternal toxicity caonndsiisntcirnegaosfedsicglniinifciaclanstigrnesdoufcttiooxnisciitnymoactceurmraeldbaotd>y4w0e0igmhgt/,kwge/idgayh.t gaDienv,ealnodpmfeonotdalcotnosxiucmipttyion eevviiddeenntcaeofsiegintihfeircamnattleymrneadluocreddemveealonpmfeetnaltawleitgohxitciotcycuatrr<ed10at0>mg4/0k0g/mdga/yk.g/dBaays.edTohnertehewsaes no results, the dose levels listed above were selected for the current study. -- ee----------n-- - ---------- Bompany Santized. Does not contain TSCA car H.24768: Developmental Tricity Study in Rats DuPont6515 --- H. Randomization Dams were assigned to lots accordintog their gestation day. Then, they were ranked within their respective lots onthe basisof day 0G body weights and assigned to control and experimental groups by random sampling from the ranked list. The distribution resulted in mean body weights for all groups that were not statistically different (p > 0.05). I. Preparation, Administration, and Analysisof Test Suspensions. `Suspensionsofthe test substance in the vehicle (water) were prepared 2 or 3 times per week, and stored refrigerated until used. The methodofmixing the test material with the vehicle was. documented in the study records. `The dosing suspensions were administered by gavage because the oral route is the route that is. recommended by regulatory agencies for this typeofstudy. The volume administered (10 mL/kg) was based on the most recent body weight. `Samplesofeach test suspension were taken three times during the study, near the beginning, middle, andend of the dosing period. Analysesofthe first sampling addressed homogeneity, concentration, and stability. For the second and third samplings, analyses addressed concentration. Samples were submitted, shortly after preparation to the Analytical Chemistry --- Group at Haskell Laboratory. The methods and resultsofthese analyses are presented in Appendix H. J. Animal Euthanasia Females were euthanized by carbon dioxide asphyxiation. Fetuses were decapitated before proceeding with visceral examinations; those to be viscerally examined without decapitation were injected with sodium pentobarbital. All other fetuses also were injected with sodium `pentobarbital before fixation. K. Parameters to be Studied L In-life Observations of Females Body weights were recorded at least twice prior to dosing to provide data for quarantine release, and on days 6-21G. 21G. Clinical signs Food consumption was measured were recorded at least twice prior on days 4, 6, 8, 10, to dosing to provide 12, 14, 16, 18, 20, and data for quarantine release; signs were recorded once daily on days 4, 5, and 21G and twice daily on days 6-20G. 2. Postmortem Observations of Females Surviving to Scheduled Euthanasia -_ 2T1hGe.abTdhoemiinntaalctaannddthtohreaecimcptviysucteerrauwsoefreeaecxhamdianmedhgarvoisnsglyatilmemaesdtioanteelvyiaabflteerfeetuutshawnaassiwaeoinghdeady -- ee-- e --------------Te------------------ "EompanySanhized. Does not contain Tara cay Lompany Sanitized. Does not ermine ~ama any H2H:42747668::DDeevveellooppmmeennttaallTTooxviicictiy SStuuddyyiinnRRatass_ DuDupPoomnat6s5t1s5 --~ 0Thpeecromriptocraalcluulteaaticoonuonftmfaotrecrancahlobvoadryywoefifgehmtaaldejsuwsitetdh tvoiaebxlcelfuedteustehse wpraosdurcectosrodfecdo.nception, rFeosrorcpatcihonfse)maanlde wthietihr vriesliabtlieveipmopsliatnitoantsiownersieterse,cotrhdeetdy.peTsohfe uitmeprluasnotfse(alicvhe aanppdadreenatdlfyetuses, and "nonpregnant" female was stained with ammonium sulfide to detect very carly resorptions. 3. Fetuses of Females Surviving to Scheduled Euthanasia Floocratciaocnh, fseetxu,s,antdhebfoodlylowweiingghtp.arTahmeeteexrtsewmearlearlteecroartdieodn:s diedteencttiefdicafotrioenancuhmlbievre,feitnutsrawueterreinae.lso recorded. For cach liter, the first live fetus and every other live fetus thereafter were examined for visceral aInltaedrdaittiioonns,")allRleitvaerfdeetdusreesnawlitdhevmeallofpomremnattiwoanss cvliassisbilfeiaetd euxstienmgatlheexsacmhienmaetioofnWwoeroeaenxdamHionaerd, for ora soft tissue designee. alterations; decapitation ofthese fetuses was at the discretionof the study dircetor fer fixation in Bouin's fixative, the headsofdecapitated fetuses were examined and alterations wfiexraetirone,cotrhdeedal.izEaxrainm-isntaatinieodnsskweelerteobnassweed ronexthaemimneetdhoadndofskBealretraolwalatnedraTtaioynlsorw.e)reArfetceorradlecdohfoolr all live fetuses, excluding the fetal heads fixed in Bouin's fixative. L. Control of Bias aInndadrdeimtaioinnetdo rcoadneddomduarsinsgitghnemceolntltoecgtrioounposf,paollstfmeomarlteesmwaenrde fceotdaleddatbae.fore scheduled euthanasia Company Sanitized. Does not contain TSCA C1: a: H-24768: Developmental Toxicity Study in Rats Dupont6515 - M. Statistical Analyses bSeelquoewn.tiIaflatswiog-ntiafiilceadnttrdeonsde-treesstpionnsgewwaassadpeptleicetdedt,o dtahteadfatraomfotrheeatcohppdaorsaemegtreorupaswtaasbuelxactleudded oafnadfftehectteedstfreetpuseeastpeedrunltiitlenroorsitghneifliitctaenrtmteraenndwwaassudseetdecatsedt.heFeoxrpelritiemrenptaarlamuentietrsf,ortshteatpirsotpicoarltion evaluation." The levelofsignificance selected waps < 0.05. `Where the data were tied and the standard large sample versionof Jonckheere's test was not applicable, exact p values were calculated using permutation methodology. Parameter Maternal weight Maternal weight changes Maternal food consumption TrendTest Linear contrastofmeans Live fetuses Dead fetuses Resorptions - Implantations Incidence of fetal alterations Jonckheere's test!" CIlnicniidceanlcoeobsfeprrveatginoannscy Matemal mortality Females with total resorptions Early deliveries Cochran-Armitage test Fetal weight sex ratio) (Covariates: litter size, Sex ratio (Covariate: litter size) Linear contrastofleast square means" i AC\ not! onaTMn TT a any oe -- " 1.24765; Developmental Toxic Study in Rats Duponcsis - RESULTS AND DISCUSSION A. Maternal Findings 1. Mortality "There was scheduled snaocrcifoimcpeo.und-related mortality at any level tested: al ats on study survived to 2 Body Weights (Table 1, Appendix A) 4T0he0rmegw/ekrg/edcaoym;paotutnhde-sreeldaotseedlerveedlusc,tmioenasninbomdeyanwemiagthetrnwaalsbsoidgnyifwieciagnhttlysraed1u0c0edanbdeginning on dwaeyre7rGedauncdetdhe2re1d0u%ctwihoennpecrosmisptaerdeudnwiitthheceonntdroolftgrhoeusptuvdayl.ueAstbe4g0i0nnmign/gkgo/ndadya,y mSeGananwdeifgirhats AaBbCosdo1yl0u0wteemiggf/ihnktagsl/wdweaeyri,egmrheeodarunctewhdeeif1gih6nat%lswwweheiergnehtcroeadmdujpucasertdee5dd %fwo-irt7ht%hceownwhteerionglhctgoromofputaphreveadplruwoeidstuhc(utcssoinontfgrcoeoltnchgeerprotuitpohne), values staring on day 7G and persisting until the end ofthe study. - Awe1i5g0htmsyokng/ddayasy,9tahnedre1w0eGr.e Tmhiensimearle,dusctattiiosntsicwalelryesingontifciocnasnitdreerdeudctaidovnesrsien bmeecaanusmeattehrenyawlere nmaitnuirem,alanidn hmaagdnniotuidmepa(crtedouncefdin2al%b-o3d%y wwehiegnhtcompared with control group values, transient in 3. (BToadbyleWe2,igAhptpeCnhdainxgeB)s Tlwohasessresesigwanetitrfheieccabonetmglpyionruneniddnu-gcoeefldadotovesedirnrdgea)dyuasctt61i-o08n0saanindnd8m4e-0a10n0m.mgatAketgr4ana0yl0.wmegAikgtghh/tdegasayei,nlsemv(eeilansnc,lwmuedeiiangnghtbweogidagiyhntwoegviaegirhnt scdaaailycnsuwl1aa2ts-e1dr4e,odv1ue6cr-e1dd8a,y1sa3n/6d3-022%10G-an2wd1aG4s4ws/aig9sn8ia%fliwcoahnsetilngynicrfoeimdcpaunactreledydartewdi1ut0ch0edca.onndtAr4so0la0grrmeogsu/ulkptg,v/ahdlaeuye.mse(Mauensaiwnnegiwtgehhietghgtain absoluteadjusted final weigh t calculate the gain) at 100 and 400 mg/kg/day, respectively. cwAotams5p0astrmaatgbihsltkeigctadolaltyyh,seitgcnhoienfrtiercoawlnat.gsraoTushple.irgehHatofmweeerv,aenmrew,aebinegcwhaetuilsgoehostsfgatatithnheaitnbie5tg0ailmnwgne/iinkgggh/otdfadlyoossw,iansogvge(erdanaleylrsawl6eli-yg8hGt) gtahaitn mcw0aalascpuprlreaedtcueidcaeubdsli(enrgeidmtuphcaeecadtdjo6u/ns1tf4ein%dalfwiwhnaeelingwhcetiogmahpntadrwbeesdcawsuiistgehnitcfohinectayrnwotlleyrgelrootwruearpn.sviacBlauetec,sa)tu:hseteyewtheoervseeernraoeltdugccaotinindodnserhsadd ~~ aver pe -_-- om noteontsTM H24768: Developmental Toxic Sudy n Ras 4. Food Consumption -- (Table 3, Appendix C) DuPonessts AThte4r0e0wmegr/ekcgo/mdpaoyu,nmde-arenlfaotoedd croednuscutmipotnisoinn wmaesansifgnoiofdiccaonntslyumlpotwieornbaetgi1n0n0inagndov4e0r0dmagy/sk6g/-d8aGy. asingdnipfeircsainsttliynglouwnteirlotvheerednadyosft6-h8e, s8t-u1d0y,. anAdt 1120-014mGg./kgO/vdearyal,lmfeoaond fcooondsucmopntsiuomnpt(idoaynsw6a-s21G) ``wwiatshsciognntirfoilcagnrtolyuplovwaelureast, 1r0es0paecntdiv4e0l0y.mg/kg/day and was reduced 9% and 29% when compared At 50 mg/kg/day, there was a slight, statistically significant reduction in mean food`consumption over the first few daysofdosing (days 6-8, 8-10G). These reductions were consistent with the orendeuictthieornsovienrawleligfhotodacnodnwseuimgphtticohnaonrgefinianltbhaotdtyhweereigwhetr.eT`hmuisni,mtahle,steracnhsainengte,sawnedrehandotno impact considered adverse. 5. Clinical Observations (Table 4, Appendix D) Compound-related clinical observations were significantly increased at 400 mg/kg/day and ainndc/lourdesdtaailnoepdecpiear,ivnaeguimn.alAdtis1c0h0armgge/,ksga/ldiavyat,iosnalaifvtaetriodnosaifnegr, dsocasbi,ngstwaainsedsicghniinfifcuar,nlayndinwcreetased. _ 4A0t05m0gm/gk/gk/gd/adyayw,eroenecornatsiwdaesreodbsaedrvevresdeswaliitvhattihnegeaxfcteeprtdioosninogf.thTehseacllviantiicaolnoabfsterrvdaotsiionngs, aTthe salivation after dosing that was seen in animals at > 50 mg/kg/day was considered the result of taste aversion and/or local irritation rather than evidenceof systemic toxicity. 6. Postmortem Findings (Appendix E) a`pThpeeraerweedrneornmoacloamtponuecnrdo-prseyl.ated maternal gross postmortem findings; all animals on study B. Fetal Findings 1 Mortality (Table 5, Appendix F) c`Tohmepraerwaabslenotoccoomnptoruolnsd-artealllatdeodsefelteavlel`sm.ortality; data for fetal resorptions and dead fetuses were TT ain SOAa J-- eee -- H2470 Developmen Toity Sway in Ras 2. Body Weight --- (Table 5, Appendices F and G) Duronesis T(h1e3r%elwoavseratchoamnpocuonntdr-orlesl).ateMde,asnigfneitfalicbaontdyrewdeuicgthitosn aitn 5m0eaanndfe1t0al0bmogd/ykgw/ediagyhtweatre40g0enmegr/alklgy/day comparable to controls (within 2%ofcontrol group values). 3. Malformations (Table 6, Appendix G) `There were no compound-related fetal malformations at any level tested. There were 3 fetuses fmarlofmo3rmlaitttieorsns(2anatd 5t0hemrge/wkegr/edanyoamnadlfoonremaetd1f0e0tumsge/skagt/4da0y0)mwgi/tkhg/udnarye.lated non-treatment related 4. (VTaarbilatei7o,nsAppendix G) There were increased compound-related fetal variations at 400 mg/kg/day that were consistent `1iwbist)h.thTeherredeuwcteiroennion minecarneafseetdalcboomdpyou`nwdei-gehlta(tdeedlafyeetdalsvkaurlilabtioonnes oasts5if0iocrati1o0n0amngd/ksgu/pdearyn.umerary ~ o a a oreo TCA" ---- ompany H:24768: Developmental Toxicity Sudy in Rats DuPont 6515 - CONCLUSIONS cUonndseurmtphteiocnonwdiatsioonbssoefrtvheidsatst>ud1y0,0mmagt/keg/rdatyo.xicNiotny-eavdidveenrtseaschraendguecsedinboddaymsweoicgchutrraenddaftood 5500 mmgg//kkgg//ddaayy. anDdevtehluso,pmtehnetmaaltetronxailcintoy-woabsseervviedde-nctffaetc4t0l0evmegl/(kNg/OdEaLy)aswraesdcuocnesdidfeetraeldweight and increased fetal variations. The NOEL for developmental toxicity was considered 100 mg/kg/day. RECORDS AND SAMPLE STORAGE bLeabroertaationreyd-sbpyectihfeicfaocirlistiytew-hseperceiftihcerwaowrdkatwaa,ssudconhea.s personnel files and equipment records will ALabsoarmaptloreoyf.tShpeectiesmtesnusb,srtaanwcdeawtaa,sacnodlltehcetefdinfaloreaprocrhtivweiplurbpeorseetsaiannedd raettHaaisnkeedlalt LHaabsokrealtlory, pNaetwhaorlko,gyDeslliadweasraen,dorraatw rdaotnaMwoilulntbaeirnetRaeicneodrdast HMaasnkaegllemLeanbtor,aWtoirlym,inNgetwoanr,k,DeDlealwaawraer.e.Clinical RCheagriaocntaelriAznaatliyotnicdaaltaSe(rpveircceesnt(pRuArSi)ty,,JcaocmkpsoosnitLiaobno,raatnodrikesn,owDeneipmwpautreirt,ieNs)ewwiJlerbseeys.tored at - LChaabroarcatteorriyz:aNtieownardakt,aDuesleadwatroes,upoproarttItreosnt Msuobusnttaanicen Rsteacboilridtsy wMialnlabgeermeetnatin,edWialtmHiansgkteolnl, Delaware. -- * 1Tw0ehrteheeNnOnootE-dLoebtfseoectrevtdeh.dis-aTsdthvusedr,ysicfo-rdfeftfeiicsntesedtvuaedsyl,t(hteNhOehAiNEghLOe)EstLadsiossdeeeqfuaitinvweahdliebcnythttahodevtehEreusrNeoOpeeEffaLentasUnaidteorfniibn(ue9tdabbyltthoetUheS,tetEsPuAbsCtasncneg consson ee Gomes? 5 H-24768: Developmental Toxicity Study in Rats Dupon6515 REFERENCES 1. DuPont Haskell Study Service Report Number DuPont-5846, Work Request a O] 2. Salewski, E. (1964). am Uterus der Ratte. FAarcrhbievm.etPahtohd.eEzxup.m Pmhaakrrmoaskkoolp.is2c47h:e3n67N.achweis von Implantationstellen 3. Staples, RE. (1974). 9(3):A37-A38. DetectionofVisceral Alterations in Mammalian Fetuses. Teratology, 4 WDeovoe,loDp.mC.enatndinHLoaatre, GReMst.at(i1o9n7o2)f.RaAtps:parTehnetEHfyfedcrtonoefpMhertohsyils SaasliacNyloartem.alTeArsapteocltogoyf,Renal 6191-196. 5. BFeatrurseosw., MJ..VM.orapnhd,Ta1y2l7o(r3,)W:.J2.91-(310966.9). A Rapid Method for Detecting Malformations in Rat 6. Selwyn, Animal M.R. Safety (1995). Studies. TJhoeuUmsaelooffTrtheenAdmeTresitcsantoCDoeltleergmeoifneToaxNioc-oOlbosgeryva14b(l2e)-:E1f5f8e-c1t68L,evel in - 7. SHtausdeiemsa.n,TeJra.toalnodgyH,o1g2a:n1,65M-.1D7.1.(1975). Selectionofthe Experimental Unit in Teratology 8. PStaatteifsiteilcds,3W1.:32(-14938,2). Exact Tests for Trends in Ordered Contingency Tables. Applied 9. USnnievdeercsoirt,yGP.rWes.s,aInodwaC,ocphpr.a2n4,6W-.2G4.8,(314996-73)5.2.Statistical Methods, 6th ed. The lowa State 10. JBoinocmkehtereirkea,4A1:R1.33(-1194554.). A Distribution-Free K-Sample Test Against Ordered Altermatives, 11. `DCeommppsutteart,ioAn.aPl.,AsSpeelcwtysno,fMMRix,edPatMeold,eCl.M.A,naalnysdis.RotThh,eA.JJ.our(n1a9l8o4)f.thSetaRtiosytaiclalStaantidstical Society, Series C (Applied Statistics), 33(2):203-214. 12. fHoarzAanradlyEsviasluaantdioEnvaDliuvaistiioonn,ofStSaunbdcahrrdoEnviacluaantdioCnhrPornoiccedEuxrpe,osTuorxeicSittuydiPeost.entPiaaly:erG,uidance `OW.Ea.shietnaglt.onU,nDi.tCe.d,S2t0a4t6e0s.EnEvPiAr-o5n4m0e/n9t-a8l5-P0ro2t0e,ctJiuonneA1g9e8n5.cy, OfficeofPesticide Programs, 13. (RXiIs/k28A3s/s9e4s-sEmNe)n,toCfhaNpotteirfiI,edSeNcetiwonSsub2.s2t4anacneds Technical 2.25, Guidance Document - = any SESS mg T80R- HL24768: Developmental Toxiit Study in Rats DuPon6515 TABLES ~ (sche aor"os TT Ia 2.9 goo" ~~ F 2 2 - 3 : : 4 & - F2 z ETS 2 Re Ea gad ged 5 EOE8.| E3.ERmEg 2E3R, abEu ER 4 2EHo.g |% 3 ofa iu Eg f 82% &d4% Be z= &= I 8Ca08 5mn% goneat lwad | 2g tel tp. 7 g2g * s & s2 . B 2 f un = 5 F3 ae ot" get :& o| 28g 28g 83, Aa, | i5 o| 38g SHe G8, REL z To] BaY Fe gmt gad EFlREE 3 - S2 3x &f4 x e|asagt%a aaAnety 2gLaot% 2fana%t 8 - a py id EBEa Hale ihe ik 42 82 42% ga = g og en in ne 5 g= || 90580s8 2227%8 gg:i% n 424d | 3 2 Co | 2E8aat d28a, Bd3s8t, gBaa |g Pr Ce. 32 iy 2s - tl. . 5 i g EE ee oo sat gone - : H z 3 Elo ne, ms, a] os _ gz 8 ast 457 gga" 8gat "3 - 2BF||8.Y EIat"e g3at a3endd JBEi%s n 52: AN 2 ZEz osf& g B|wzgiEvRz4T3is aibTofn haaRe 2Bi0g . FR] aiEh, R2ad, 4a3t, paxaBtsBfsf 2 3 . co a. |E5El5Ee5E8gu0nE8yb 2 =| sda gh 3x aidEpityd i 3 $85 Z 88 d F 3 g FgE| Cgia:d g 5 . 5 | HE re go oo wr Tod3 7 5 =aY 8aY 238 agd 5 Z22g 7-3 ||| 92u%ag H3o%5R8y 1v3Sa8sa 223d8E44 E5 J " 8 83 a%q 2h 28y ZRg - 2: 4 2g 1 Z3 833% 3% Mseda a3ly <: ota nz he gz aZ | I] 5wt3 gGatB fZ2iTn gBeg H I i | }3 H3e oer & ~3 El Ei 5 nts gon? ys oon : $ 5 4 _ : 53 Z2| : i 4 4 a. = 5 52 :1 8 3 Zz 2= El i 8 |u|, 8, 8. af [I Sg 2 3] 82 238 gq In8 pL] gE 20 ; 28 ga as ona oes fo SOEEiET |8g% Ei ;gab gad oaEr 5 Bi |afw ale gle 3B Gd =. igdsf 38 35x 5Fo] | 2238%s H9O8Rs H9O8Fa S"08N.E[E3LeWSBgE iis 3 282 04% B83g F VEE F 5 f]F [ee ig3:i EH EN FE 8 OR JE ea anes.000810 AanTSO - pompany Sen &| --_ i5 g zl | | :& # - 2i 3i a 3 ; SF g3 08 SR Ez 3 2 fe o 8Zz 8H%g | |98s%q 4923884 qT3R 0ARE 28" 8 of = 3 - EL og z3 BERIE FEELE2N3g BERaEy rg 3#g< Er 2zz 2] | g2a8ng AEEREvqRE8JEiaAm RI3N = ! mre Te Wa 18 + | de RR QU gla 823. = 2 sg 8g PRES o 5gl = Et pay sanz0 2: ; stein TSCACS= i 8 = 8 Z{i1| iB 3 -i ! RE g i : ::-i oF:: E1iNd, Sijsl8 5 vo n 8 :i:f3 E og, v3, he, td5 Eg85Dce7 ey EZI ARz FdF | P18gERgyERgAenISbLaglfPoiaooufidiE * fs | 28g ohefa 3Eh8g ae SBHRieSlr5etH.h INepiiE | 3% HL, 3 oz liLz 3ie5i7:e%l,B 3 s Fog Joo companySanat Doss aconTS 3 i : i : zsZ2z seal wooomomooo00 oEdii _ a2 8> f---ii nceccnnecnnee 5. Sg go & FH Bi 3 2 gi 2 1d : : 22 giPdE EE58B 8% 2gEE 5 |5f i URE HHHTE Set . 3 5 gompenq=tunnaet 0008m rsoace: " H-24768: DeveloToxpicimtyeStundytinaRalts DuPont-6515 -_ TABL5E REPRODUCTIVE OUTCOME# Group : Dose (mg/kg/day) o 1 ur w s0 100 400, No. Mated 2 No. Pregnant 2 No Aborted No. Deaths o No. With Total Resorptions No. Litters 22 22 22 2 22 22 22 o 0 o o 22 22 212 No. Live Petuses No. Dead Fetuses No. Fetal Resorptions Means Per Litter Mean Corpora Lutead Implancations 306 3 15.502.23 30.49) 304 4 15.02.50 14.02.29) 291 o 15 15.7(2.69) 4.00235) 286 o tl 16.4(3.00) 14.30.59) Resorptions: Total 0.402.10) 0.20.39) 0.7.73) 0.70.20) Barly 0.402.09) 0.20039) 0.3(0.55) 0.6(0.58) - Late 0.50.21) 0.0 0.40.7) 0.100.300 Dead Fetuses, 0.0 0.0 0.0 0.0 Live retusesd: Total Males Females Mean Fetal Weight: Total Males Perales Son ganio 13.3019) 6712.06) 7.2(2.00) 5.50(0.28) S.64(0.35) 5.38(0.27) 0.48(0.14) 13.82.20 7402.57 6.50.65) 5.49(0.26) 5.64(0.29) 5.34(0.28) 0.52(0.13) 13.4(2.52) 7.52.70) 5.92.22) 5.40(0.39) 5.56(0.34) 5.23(0.43) 0.55(0.18) 13.5(1.66) 7.001.487) 6.6(2.26) 4.76(0.29)% 4.87(0.30) 4.65(0.29) 0.53(0.13) ba OStnaetiasntiimcaall parneaglnyasnetsbyarestnaiont. conducted on mean corpora lutea data; these data are pStraensdeanrtdeddefvoriatiinofnormiastiroenpoorntleyd. in parentheses. d pSetratilsitttiecra.l only. aTnhaelysmeesanarneumboenrlyofconnadluecstedanodnftehmealemseanaretotparlesennutsebderfoofr liinvfeormfaettiuosnes Number male fetuses/total number fetuses per litter. + significant trend; p < 0.05 Note:wereThgetaptriesgtniacnaclylyraatnealdyaztead, uasdiunlgt tmhoertCaolcihtryand-aAtram,itaangde ttehset.totaAlllrelsiotrtpetriomneadnata -- tdeastta. (eFxecreaplt wfeoirghftetaalndwesiegxhtraatnido square means. sweexreraatniaol)yzewdereusainngalyazeldineuasrincgoJnotnracsktheeofre'lseast -_-- 30- `Company Sanitized. Does notcontainTSCA cal H:24768: Developmental Toxicity Study in Rats DuPon6515 TABL6E INCIDENCE OF FETAL MALFORMATIONS Grow: 1 n mr w Dose (rg/ka/day): so 200 100 sxe Tou Tenis Anus + Tnpertorate Tail - Filamentous No. attected 306022) s0alza) asatza asst paw ee i oo inl oo oto} viscera Yo. Examined Heart 4/0 Greater Vessels Double outlet Septal Detect Yo. Affected 02) en sen use -- aw i. -- -- aw o@ em im oto) smo Yo. Examined Mares - Naris atresia Yo. Atfectea 102 as7l2) sae usin a --e -- ol am om ot EE -- Te containTSCACET CompanySanilzed. Dogsnot H24768: Dovclopmertal Ti Sud in Rass DuPoncssis TABLE 6 (Continued) INCIDENCE OF FETAL MALFORMATIONS sess cafrsorwams 1 0 vom oa wv ae pr Yao. ngtsec--ted sow ow wen ow men ew meen ow o Sosmat.SSFaoumlxratboaem nrrnaeaetxaioapfompniasnTceerv adaasxniaenngde,xpartsetese erssoetsde.dh,aivseiaFbecm etitouhsdeisenFfgewipioitotsha rceoerdmer)wbaiecorhrf0em saBtehtveeecentsseedfso(re wwhwiittihhemtehsseistem Leeidswwted BfEiuoteTe1acCrouaintytseochSrnhsiactaeltaderrsoprasciotehnast ovecrceurrBeLdesrdtuiroinntgaccehde soknaeleccoaosl, perotceessmainndg, s11t0eEp;, thFhee, ~ GGGrooOupp fT.rr fr DbhaiasmmNeoe. fgc4usunsnsmy3 mFoeecrtuseuesss Nio.y5, 6,--a--nd 11 Some Gotusso ware damaged during sviseeraiions A Iie of afacted fetuses and Corretponding bones 18 presented tn Appendis 6. No signsicane trends vere detected Note: SCtvaetriasitiicCaolvewllaynsdecsoiaaviee oBnylysicaonndtuycpteedbeoan ptrheovinedmiveindutalypeinidpooiinnites.. ThThee TE eee aca company Senta= LH2-2467688:DDeveelovpmeenloTToospirccimltyyeSSuunddyytiinnaRRaltass DuDuPPoonnet6s5i1s5 --- TABL7E INCIDENCE OF FETAL VARIATIONS Grow: 1 un m wv Dose (ra/ka/dayi: 0 so 100 "00 DEVELOPMENTAL vARIATIONS exten Yo. Bxaninedd Yo. Attectad viscemy Yo. Examined No. Atfectea 602) 30st 2seiaz zssian) ~b ol ool om) wz sre 15202) nasa oe ol ol om No. Examined Yo. Attectea seam No. Examined - Rb - supernumerary Sternebra - Misaligned Yo. Attected 102 se asa) asin ol oll ow om 32 e702 230 wean) we ou 200 sane :@ aw am wel ue 200 son TOTAL WITH DEVELOPMENTAL VARIATIONS we we man an TE (in TSCACE! paed. eD eeeet-- company S wo H24768 DeveloTopicmtyeStundytinaRatls Dupon-g515 - TABLE 7 (Continued) INCIDENCE OF FETAL VARIATIONS Group: 1 Dose (ma/ka/dan): u m wv 5 100 "00 asIAIoNS oie 70 ReassED bEvELOMEN sxe vo. Bxasined vo. Attectea ose) doalzal assim zest ol oom ow viscamas No. Examined Kidney, papillae Small papiia - size 1 Seal zapila - size 2 papilla - size 3 Yo. Atoctea wi wen men sen 263 006 nae ean -- a 2m - nan um ray san sen sm ae nu ena nna seo wo - Yo. Bxamined so. Attectea wim ol awe ow sen ot sin om sunt Yo. examined Mandible as - vy Retarded ossification SSktuelrlnob-raRetarRdeetdardoesdsiOtsisciattiicoantion so. Vertabra Atecte Retarded ossification ssa an amen amon wo ---- sao -- sm ---- nay 1 aoe wo woo aw sao wees 20 ase aus sun sun sso ET pompany SAE TscACEH H:24765: DeveloTonpicmiySetundytinaRalts DuPont6515 TABLE 7 (Continued) INCIDENCE OF FETAL VARIATIONS Group: 1 Dose (ng/ks/day)s 5S m w 0 100 00 TOTATLO WRIETTHARDVEADRIDAETVIEOLNSOPDHUENET nen sz sen man TOTAL NUMBER FETUSES WITH VARIATIONS sey seo sewn meen a b FVuoanrrbieaertaisoeenxsoa,fmianrreeeaddieannxgdp,reasfzsfeeercdotseadsh,avFeeitnubcseleeusndi(nrLgeipttlteahrecse)dnuwomirbtehrFedtaaufssfheeescste(dfLoivrtittethrhse)thleistleidsted d@ DpSautpeaitlitlsoateit;ceaclhtnhieacnadaleltyaseierlsrsorasrfeotrhcacotancdhuoccctsueirzdreeodanrdetuhpreriencsgoennbttiheneeddskfeoilrnectiiadnlefnocrpemrsaotcioefosnsisnmoanglllys.terpe,nalthe efxoalnlionwaitnigonskeletal specimens were disarticulated and ths, were unavailapie for GGrroouupp I1I DDaamm NNoo.. 66a4s8s53573 FFeettuusseess N1o1.75, 6, and 11 GGrroouupp TIIVI DDaamm NNoo.. Gcaassss3ess FFeettuusses 6-9 and 11-14 - + Significant trend (Gonckheere's test); p < 0.05. Note:GveraSltlatitsottiaclalanadnatloytsaeiss abrye eoxnalmyacroendpurcetseedntoend tfhoer iinndfiovrimdautailonenodrpoyints. The Seldne otconn tain TSCACBM H24768: DevelopTomsicetynSttuadyiln Rats Dupon515 APPENDICES TT pm otcontainTSCA 24768: Developmental Tosi Sayin Rats Drones APPENDIX A Individual Body Weights . - poss onan5A ----g--e--ized-- : ------ H24768: Developmental Toxicity Study in Rats Individual Body Weights Explanatory Notes Footnotes a Matemal body weight minus the weightofthe products ofconception. b Pregnant by stain. Data excluded from the calculations. Abbreviations. ---- =No Data DuPon6515 --- ainTSCACEY company sanized.Dos ao 3 -- H-24768: Developmental Toxicity Study in Rats DuPant6515 _ INDIVIDUAL BODY WEIGHTS (grams) GROUP I: 0 MG/KG/DAY anNnBuEaR AYO DAY4 DAYDSAYS OFDGAEYS?TATIONDAYS DAYS DAY 10 ssiessss2107 sississs22s2 sSiisess33ss GiSeisssiia GiSsessssssa GGaespssesss Girgse7d1 GGiiggss776 Ssaasssseerz SSaassssse2n csiass0e1 22730.00 aslo 225562.47 2620 2w2e0e 270 223703 2304 220873.03 261 2290s.7 m0 220301.s8 aly 22380000 z2a5l0s7 22517323 s26a3o6 22598s3 22688817 22796721 22570000 225370.03 2e6e1.s6 2asl0le4 2v838.628 80i 228689.07 s23l70o0 asess s a26m5is 2e3e0d a2v:a4l2s s2saao8 22096..00 22es6ll00 226675.74 2211591077 22e91530 228e39l7s 22849.75 23504037 2203320000 2255960s6 22660637 2276m9.2 aanlis s28s.e z2ee9a6 a2issllo0 226626s7 22e100l5s 22784532 220071 22m6247s 229065.33 2200l000 226417s8 2266050i2 2216s45 m2ol3s 22ea7s 229e2.s7 a20llo0 2266313s 2amaie e2l7s 2296011 22mmee70 2299a3n.2 22366ll00 226608121 221880si 22189107 22e1s3lss 229950.64 s2a9i5s.7 2560 we 29 2931 2083 2995 305.3 otcontaiin n TC!TSCACE Does! 9- pompensSul aes. Doovp erssue isas ours ~ ison. so esos (rom owBcsEr. 0 ereons men en me ETR-- E hes au awn sash Er emp - ganized? - 5.20768: Developmental ToxiStucdyiintRayts Dupont6515 _ INDIVIDUNL BODY HEIGHTS (grams) Gaove 1. 0 wa/xa/oaY "soomaons rie wis ossmworacesmazwiona ow ae a pGCaattetioa Siseae m W moIo mEsmm NGalmEe iwme an s eBses pfSiaiaatssaeaesd Guanes WMHoiooedas mim WamDmm mE uWWsns men m3anes wd GGGiaotsseeissa Cinses nWEeosOE oNoeamsd Hel Wr mddenin dn bboienns fl NwBeid aml pSrGiietseds Gis WNBeeSdr WI AmmseE mr Msdemelnss a amamannn nen oawbe Rd fCCiiinnatseaesra Gioses MmWrSEommmess Ma wr waWnae Ee aWmmhlle aed Namsss ES pCiracor mTaoweeds Eammmia amsss aams EE mpm SS oss. or cscace! 1.24768: Developmental Toxicity StiundRayts DuPons6515 --- INDIVIDUAL BODY WEIGHTS (grass) Grove 11: 50 O/KO/OAY fr ER mo sara owDeavs oFCGoEwSsTATIONbars ows DATO GGsiauasassszz1see GGaiGaeasssase7 GGGooosssiiaez1 GaGCaiosssssae1sz CGGaaosssseeass GSGiieaaassreasso prGSeaatosseeods1 Gee 23Ti09o.l00o deeeessn mmali2a samsessises aaavm7as dagewmrsos 3a2ss00is007 Be333n00 eddeasvss aaeemasss 9 mames 2as2eesso oa2as6seass aa2mssos 3HZ0e00o0 amdmeass aaamwwae aameiess dsaemseesss aaassmlsao 23a80m02s7 BBS505000 dGdoaw0es sGaemeeoss aaamsel as aaoaessreoas zageesalaes aes ams N$G085050 GGIeemenan dGdeeaaaa mswelaan daaeseessso asaeoslas a330ms0e7 ZBBii6o o5 ddGeeessa amamomapa aBsseaslisss maamemaaas meaaamsss 2aa8sm90se0 DB900 I aGaeaa daa mGesa ass aamlis mle zzeean sale zaemas aes asmsss 26903 fae ed Bas Be Mel deo amie notcontain TSCA= rT pap Se DAE HL24768: Developments) Toricity Study in Rats DuPont-6515 ~ INDIVIDUAL BODY WEIGHTS (grams) GROUP 11: 50 MG/KG/DAY WomwsaenR DAY 11 DAY 12 DAY1D3AYS oDFAYGe1s4TATIODNAYS DAY 16 DAY 17 spurses10 sis525 2Is6a1 Ses 2s9o5a.3 08 2a9a.2 amie 3a0m0.s8 32s 33093.02 36s 330s82 34 332640.078 369s s8i48s5s3371 siss3e 2S08103 2053 2s8o6r3 2s 2d.a0s 2972 2a9m5a7 028 2g9a8z4 3074 3m0e5s7 lel 3s1e9s6 367 sSeissssaa1z S4ssas M$1e2s3 2i9s7i3s 302260 30as aanlso a3smlzo 3e3e0l0ss 3051 327 sao ez ans slo 32s SSaassas7) Gassez 2S705801 3302 0a7z ama zaerslao amie amslss 21 e29l9lss 3022 3zias oes a32s7s 3s SGeasssseers sess7a 2S2e70o3 31 asleao 337 eademadae a2w9s1l77 s29a9s1ss amaze s31e00os sis 3328s1 3m pprreed sisses 2S8081035 29905 2008307s 3070 03009041 ns.z 332000000 2200 3e0ssils3 3:7 332s0 soz 3s3a1s4 3a pprree 22833222 22935573 20002 20990a 3a0l0s smszs d3i3ss sSiiss569000 2s7i7z 2290002 essoes 209320s0 3w0i0s2 3s0a7sss 332:52131 me Joosnotconta" TSCA T---- H-24768: DeveloToxpicimtyeStundytinaRalts - TDD 300% WEIGHTS (gcans) croup 12. 50 vo/xa/onY w. ens oar marieowsooir eGessazimoanra or me fGpieressse eSmeissa Bdseeen: Easmdss Wmamnso adanSns EGfiiiaeassssre SBMneeoe dBseebeEi sdsamena mbdewdss aaammmdds prfGataszeaetn SmMEneooaWdsee amWmsns anWiina aSaRnns pfGraasseeesd: amSenneomdlema Ssmmasn Gademieenn dweles pGGiaeasnenas SSWheaosBnaer mmimnni amaimnns Baneneda pCcriiaate SWSeEa dndEebsd daSnmsse @imsoeSn we GGGriioossseetee uSBeees dedended EdSmdsa eidense 3BESE Geen E30 ms wna DuPont6515 ---- ems od, Doe1scontain TSAcor 124768: Developmental Tosicty Sudy in Rats Dupont6515 _ : TVD Boo WezGiTs (rans) GROUP 111: 100 W/KG/oAY urnmisn mro mwa owoears oFCsozwssmarionews oars ari Gfpaeseee n fWaeson. fEaealss mBaeemena daaenmdds dwamSes daaoeins Boaaeease ctGiiisseena0 fBIoaono mZdeeiid dBhaeenss dkdeleys dBEeREsDOEmaDmnDa Bhseiels pGpretetrs Bffaennool anedel EdaEnS mmDaess HEfNemDss mdbaoinna dIaaseds Gpfitasesstsesr EFBelooo BEGoeenndo odmmenns mammiaenns Bamsiaens hdsaennn 3adeeDeds GGCiaisstssee fBEeoooo mS Een Rdaenes dsaenna dedaennn Bsdeeanad daBeeEssd pSSiersenen Gfweeene BZeeeddd ddmamnn Bnmedds mdieagdnn Emmnnn daensd fffieiseeesss omiaoen Zaaamlne mdmoendn hddaeednd mdEeSnn mGEeennl sGdeeode fees hes dBm OE OED mS ad ------=& . aETDLEs EtainTSCACE 124768 Developmental TonckySudyinRats Dupont651s _ VIDAL 30DY WEIGHTS. (rane) Group 151: 100 wo/xa/one jToe own ows ow BoCavs oGr assnTaTiown s owas awa pJ eesd FmwenEOmaFmrs MwR ets E Mmoas eE mmsoOEmsmie swe ma fpeaslss i Efndakkdeelr RlEmnn BEaenns Eamnne amnmssl mnneed GcGiaaasssettse m m moi aom mmoRmomomasms namntnn ooEmmm pEwesds pGpesee mrDeannomemedt mdmndn maosnm EnmNanGd mmmlsn om me cceaoesvnes BfDaese mBdeiEi oiameeoa udmana memess aemmdn maWene peconenn mmBeIis lBBeedss mmdyse hdHheMe mdMesnt EmHmiEsn wMso GGeeoesdss mLBoiidoemmrie BdaEms mammbdd nmdnon mEmdSn mmmsee pH moomoo ERD mm Eom -- espn deo BERRIES TSCACE H24768: DevelopmentalToxicityStudy in Rats ~ INDIVIDUAL BODY WEIGHTS (grams) GROUP 111: 100 Ma/KG/DAY ovenr trie DariDAYSOowFa2G0ESTATIDOANY ZL Day 214 Gciaassszi1s G6i4s8s5z370 GaGaassesrs GaGnassseesn CGaassassso GGaassssesna GGaassssreas SGaaassser SSaisasseons GSiiaassooss Gparoen Jased.7 daee7 daemsees daomnea amisa aJalse csaerlrs asmlos amsioo 2a0a0a0 dsellss adreess saeeslss aamoas aanmao 3J3e6s meez osemss aamoln ;04o2 3331s eeosss aawaen daeems 2a9327 3F6sh Saeedd doail ajoseas nsiaas MMeelro ammeie admeao acenlaa 0a3ss NM8s3 maemal admasd amoas aatses JBeE aanme a a3mwa aasssso wdoiees 3B5e5es ssmess easazr eamsias aamos S33z3 emeilss mdeaez salwsz aammoy Dupont6515 -- = pompSan notcontaiTnscACE! H24768: Developmen Toxicity Sudy inRats Dupon6515 INDIVIDUAL BooY WRIGHTS (gras) Grown 1: 400 a/xo/oRY oseumss myo owe oweans oFCcoamsazarionbare ows mario fsCosnessae pprrreend ccpssriied CSstieae Spcaetsnsyeb GSSaseseens GpCiutnnezsaen ppredd TBmelaloo dBoameseass aaammsao adammways Msanaes EsameRssDOIvRs3 SBNa9lo0 BaGes0e dedahesia esaeasanss sasuwes ssneaoelass w23esa dIMooeonw EEEddl dmEeelnd aBNnSsd EmBmOenSl mammnEd Ea3EnS WBoeoooaBmedl ammse afemss sdeaan aEaIaD aaensn ea2ee0s dEmeeSls dEaamesa aBanda ddaamnne admmmdo dRaeesls ameeeesooaaaemldd EEmenn adEseIssD EmnDns Rmkiinn eE0SS SaBeeoo GEmelha emawnse mmameSe idseeadls nMswDooDn aIswnelnn HBoooGsm mamSo aEmns aEadn sen Iddad potcontsid TSCA cB! -48- anySARE" " 124768: Developments Tosi Sayin Rats Duponcsis -- fr -------- Group 20: 400 a/xa/one WseEns own war ownons oEp wceesmzzonBas owas ow Gf-- riime mEsaeeo emmeonso damlmn iEamSmo ddamanan hBaewese asne pCPruran E WmooEmoEed mdmsSn IeBSnn madadnd mIIdns BadaDsn fGGiuiaaesssee DmneeensoondEmnDiroodmmwlnn namednl EAmNESDS EE niS n hidd fcCiienassen E mmooEC BHeIdDREmMS mde mdaaH n mmendSr3Bed NaD fGGiiaaeisnsssa hDSeslenhBsmesd mmdmnoa dmaamnnl EaameDes BdmaeEsss mssesn GcEaiitstetesrss 2 Bfee5n RBBeeelsl mDEadYa dGGaeannn dsmwenso Gaaannsn mseese GCpiiassysseo ifBserndae3sd mmdils BmdeeNnn dadeds BmBeiinn Nh aa meu ms mn Ed We Md EE notcontain TSCACS! H24768 DevcTosls oSypnmas ~ Dvioun soot WEIGHT (gta) arn 10: 400 vo/K0/one sBoas awa ownones on aEssmaRrion 0 owen aaaammmmmo mmmennnomwoEgeEgeRomaEWmgeSe: mm8Hasss amEamdds aaaammmmiee moBEnmmadoommmgs mR WoEgmts omWeSd EaaS Gaaaemmmmeea EEodommnnoRomnme3n omm mErsSia dmonnm mmnssn aaaamwwweenn mmmodla3e W oWnwEaIomZmWmnsodmmmnnniomaamsnnd gGGaauemmaee Bommemsensm MmmsSn m moERmnCzsoommw Mngm Gm Bmmos aammey EoDasomMms NmmoaEtn BRuo Duramsts conanTSCA -- Eee , Does nO H-24768: Developmental Toxicity Study in Rats DuPont6515 APPENDIX B Individual Body Weight Changes Toi Campy Sek contain TSCACBI H-24768: Developmental Toxicity Sudy in Rats _ Individual Body Weight Changes Explanatory Notes Footnotes a Maternal body weight minus the weightof theproducts of conception. b Pregnant by stain. Data excluded from the calculations. Abbreviations ~---=No Data, DuPon6515 2 comp not contain TSCA CB 124768: Developmental ToriciyStudy inRats DuPont-6515 - INDIVIDUAL BODY WEIGHT CHANGES (grams) GROUP 1: 0 Mo/XG/DAY amEEaR as 68 81D0AYS OF1G0E0S3TATION3214 146 618 ssiis8s1270 ssaissss2z02 Gsaissssy3ss SGiissssiia Girsessa prSiaessstes sGia8s5s7e1r s64a8s57763 pprree sGiesssssezs Gsiisss6o0z1 20004 a1l0os a1lss 2u3s s5.s6 a1l5sa 725a2 2126s0 1e1s 1 le asss m6i2o 211as z25e: f15r0e5d 003 s 1 sh wis 162 is w2l% 27a m7a1 2s owslss al 21900s ass 0a'0s 1 12 8137 mal2s 1 se 122 167 22%2 22025 sis als 2ale ave 1w0o2 a7 1s2o2 71 11008s nh 11s4 So 8s1s mr wsrs zis 3m7la ace 152 2a nsl2s oma 1s5s2 wiz u5l7e oul 17232 nl w1os ul aslss 300 10071 7 108 aalss ao ewlioz ash ae57 cs 1126013 me 2w2s ss aasss 157 1nl7s s1s1 owslss 11s0 1w0as 226s2 sselss no 22 wis ws 2 los ses 5 Company Saniized.Doesnotcontain TSCA CBI H24768 DeveloTopsimcyeStnudytnaRalts -- INDIVIDUAL BODY WEIGHT CHANGES (grams) GROUP 1: 0 MG/KG/DAY rnean wp em enones or eGsmTsATION saGGneosn1ozy SfGieasnnaes GSGaainaagsnsa SGGaaonoggseeoss pprrGoeester pprrCaesestar SGGiaasossscioaen:s Sanco HSaasomBmias amdaenns aonshn BEl3ss0 nmmaiaoanaasbnn aa aens XB3E0i10anbmaenomDaanes auasis WB#aa3o mmBnnr moaonasans a8RhSS zBB2eE0 aoWannae dawwmne sBEende ZXwosoodmBsso Noaewesss eEEnnd iw Hoosiahonwl aaemwnsd 8dhnnl we nami 83 DuPon6515 - = `pompant ST contain TSCACE! 24768: Developmental Toxicity Study in Rats DuPont-6515 _ INDIVIDUAL BODY WEIGHT CHANGES (grams) GRouP 11: 50 W/KO/OAY fTeoan een edooars opCcahsTraroonme wes 16 GsSisonseesztse W2Wwisooo34a3n owonna:d BmBiad Bss1rs0 Ra7Sfs nBmSSo GGGeiinensrn W WfeheodmwEo oB3mSon mnn3an BaBrna owhunsd HEnSln fsfiiniasiie:r oSiy SThRRonwMnnnonLBasen aEuNiE mhasnm EEAenn icptheie aSDneosmae33 oogwnnn nBWsRS EBSSSn RBuNSn 3Enddn fppirreee FS"e56aW3nE3 Wmmasn wSNsaLowaRdeIs mhwl3n 3nWsn SSprtnaess wwhoeo0 eihse RsNeen nBkssa BaNs3s mBEirSo aBn5ns3 pppirrree BwwoEi oot Gean oSw: onBesoi EWBDSd RREEEE B3sn2 Seo Ena Hn 3 Ed nd EE -- tain TSCA CB 124765 DeveloospcmSeyninRos _ os 11. 30 worearone SE ------ Jy sus 07 somason -- LL 56 pompansya edcenten 1.24768: DeveloTorpicimtyeStundytinaRalts Dupont 6515 --- INDIVIDUAL B0DY WEIGHT CHANGES (grams) GROUP 111+ 100 MO/KG/DAY JAead we G8 edooavs oF0G3ES2TATIONze dele 16s suGSaapnnsss1aasr siGaansssa0s sGsiiiannsssaaa3ss Gspairnnsseesdrs sGpeirnnsseeess Gppirreese GpGiiraassessss SSiiasceooss 1m13e5 a27s83s maslass 111632a7 1an0lsse nmaass 2229 n17o whbr mwhe oswlas mGebs smao 2zaa Buseno malrbss aaFess ER02C08 s i5 oa mmnn 2sm00sas 2w0sa0o osoellsss ma1li5s amaesasl ww0o7ss amasl2es 22s1ise w2las5 e8li1i wBSnis 111hs7 as3sos mhalane sBwsaaa 27a05o a5Glhe waalsss 1ad2olsas w5ir2 asmlass amaraos aufsos HhelIno hauelnse a07525 alllses 2oD6saa aasledss dfes 2hae o2a5n an0h 1nss wRon onnsd -57- Eee Sosa otcontainTSCACB H24768: Developmental Toxiiy Study in Rts _ INDIVIDUAL BODY WRIGHT CHANGES (gras) GROUP T11: 100 Ha/XG/ORY Jmesssy 10 om emons oF ecasomazion cpfiurnsiest pSCiirsnseeeys SpGiutsesteiee fCCiissnssseeerss GGEauannssssnreaer paSCuitnststeyar pSfrisois]oess pre w25s30 wEwane mbheasene amdzhn BESao oaRwDs dddealns amansE Ee wehoaoomnsnoowdomlsns woaanhn SnE1a0ooaLtnso EdEnSn nnandn EsHeEoooodnamnooBmmenl Bauani w"Sai5a0Al3n mmmnns 8uas3 WRS3Ee0 mEhunowaomsaans noBnnaa anoneoomn un Dupon515 Sanitized.Doss1! potainATGA5H ---- reeEE e SE rere 124768 DeveloTopimteStnudytinaRalts Dupont6515 _ ADIVIDUAL 00 WEIGHT CHANGES. (grams) anos 19: 400 Mo/xo/oRY sSmmson wo ee enstas orEcEeTsmation wae aes GGcaiiseeasssee WWweaeaaslanoaWendr gsonse mhdoE ainnee Rads pGGruaeosyns ma Ss: eaLa nes aohand WwHdIe Banuim aNNss EEaBnd ffSaaisstttiaso SSS5a0adedGerme @awmndowLEEer aaWiEm d2ud3r naBas GEriaassseeo TBaoiomonee aa33 oaBs o3wn a3ds EBnS fGciiosansasenesor eo rson ldnl sh a wBweee wmBams 43s adoems pCGruieearrar SosLoooamainme RdWEn eaalues aaamnn NoNaynd BRRddd CCpllaaesseess Wweeel ooZmEnnnooao1wnn BTad3 EMWgln RfaDdn aBiSn pCrass wiLomnao nNss BaDn aNn guno BdSE ScACS sizeDdO .aotconan ee -------- 124768 Developmental ToxicityStudyinRats _ DIVIOONL BOY WEIGHT CHANGES (grass) Group 1v: 400 va/xa/EhY Jaernviias wa zm eaonats or Geesataetion caCfusiaasstssse GCCuoaaasnnssez GGCaaissaeesssio fCGiaaissaee:ss prGGaeisesr ppCrireena GCCiiroaossssesoe an aw wsa ehomn da o eWeds a8Sces wsFnEoOeooBuynooanr noaonw wE ERiT a oon mioouews 823:2 wwwroeunnn3ngowoudnad oo1nds B woiweBodme wwBids gDnnad wwwriooooBfuyIouHdmsdm Ba BI aed awuiees aaERRnninmyI oWunr I3iE Duponcs1s (ain TSCACE ameod,0-- 005TM -- H24768: Developmental Tsiiy Syn Rats Duponis1s APPENDIX C Individual Food Consumption aomanTSAO pompany Sanitized. Dogs 11 H24768: Developmental Toisy Sudy in Rats Individual Food Consumption Explanatory Notes Footnotes a Pregnant by stain. Data excluded from the calculations. b Due to technician error, food consumption was not recorded on day 8G. Abbreviations ----=NoData Dupon.6515 = I-- cat , DoesMO contain TSCA H-24768: DevelTooxpicimtyeStundytinaRalts DuPont-6515 -- INDIVIDUAL FOOD CONSUMPTION (grams) GROUP 1: MG/Ka/DAY ANonuaERn as G8 80DAYS OF1G0ES2TATIONa2 a6 eas ssaassss2?0 ssaassss22ze Ssaissss33ss sSiissssiiess GiGsasssssa3 Gipsrseso psir8e571 Gisis8s57763 Gississseezr ssaasssseosz spasce01 22.64 207 2asss 264 2m6h2 sr 2al0s asa 22609s 393 22s2 28 oaslso 3008 aal7s als oaamsis mls aalss 223 22:006 aslo a2s1s sls amlos de 235001 a1 2z2o 24 nallss 1 m mls l mln 2 als a;m2ls aes k36o as 30600 no a2s0a4 204 o2assis ass 227 203 aaslso 24a a3s0aa 20 3 ae 335 ae29ss03 =ols siz a2a2 253 2200a8 on3;:7 zis 243 3ze4n 361 saies srs sueles 3a 02:30ls amllss 20s moas3is 2a e26ss me 22a 7 263 lsess 3s 2sa6ns sale 22082 242 awsss 3:4 2a2slae 2s a2l8s3 26s 22a85 308 3306a 0k 0sias 327 005 2s a 26 aslo 4 210s ized.Doesnot con!ain TSCACFBl penis H24766: Developmental Toxicity Syin Rs - DITO 7000 CoSONPTION (gears) Group 1: 0 vo/xo/onY snneon wa oahtasnor casmaerinon GGcaeesssir SfGeaeasnsee ffGiiaoossneeass prGGiiieessee prGGiaiaoeennds pGSriieezsees: ppbrrieeeyr pH wwre BBm3na0 Ekmeso mwweer dBB3n0ioBnd 233010EHdnn RS Bonyer B8B3S0 kndd RiFEioBnn kf m3E1o0 oo@E Nnn LEdn a3$30n00 fBR3Ed0 aREdSs aon om Dupontgs15 `Companysanitized. Doss contain TSCACE a H24768: Developmental Tovciy Sudy in Rats Dupont6s1s -- INDIVIDUAL FOOD CONSUMPTION (grass) RouP 11: 50 Ma/KS/oAY f= mo ses edonrs orCcaeesrTaTionCaras ee ee GSpiiaeesszsz prGSioeesstrys pGCiarooisaeirdz pGSiiroeessssesrr pGSraocezseesr GGGiaeooassreess0 GGCiioosssseoerne Siacoo a2mes abmiiee bnwiia BB25E90 33mD8s RoB1ms0a a6230 2BBa3om1a:6s moo@mbia apamaos aBnuIes aLasnoe aa0es. Z2mas5 mzolsnes moomwsae amoaasn sRLe3lr0 ddRenSs Na63n% 5 ZZes smwlshs mbblasso momnaes sRReIn s4WesL sRnenSd Zamo1ae awmsss abooixs3 0RL3a0 RjhnSe a8RsD a8NddS aZZis3o 0 bmmln1s nkhess kfdoelns BBeLal Re26Es. uaaenss F25oa0e SaaCeaSVbbsaoSE 1BmoaSE TB@onSE +3ErasSE 1aE4ss B30 wi we ns #7 me 3d schCe!\ TT eT eet concn FE24768 DeveTlooi pSumdyenRnts --- INDIVIDUAL Fo0D COHSOWPTION (grasa) anoup x. 50 wo/x0/oRY foanoad ro ATHEY-- pcearsesnide BBwrre BmBmia: =mzfal pGarnny mnnryi ooommmaa yooaomme a pGree oBie 0 kEBieS BBBSia pccaareesar BB osIoEnB}S BRIsIa sspereree nnBiionE8e:3 onamid pporwrer] nB3as BBmIs3 moBeeS ppPrrred FBnEiiS ooTBnmAdt Bs 3 ns 55mm Duronests Te meen gesnot contain TSOACB! 124768 Developmen Toc Sud in Rats Dupontsis - nipivIo $000 CovsETION (rans) Group 132: 200 ve/xo/one osnuow sen emotns orecemsTarionThan we eas cScaiasais ln Ha asoomnwao mm1asa smEeLT aBRmRaa 0amanl wWnadn cfciaaaiicine maBheeooooawndsdomdnieds EGaDln dkBdE iHmHnh nabisdd fGcaaastiiane E @@nLM ooooI nndd BEoaasr Raannn BaaRn: nmEndi BBBeld Gffaaaccsiies aESiAnoooBnoBnamEoo@omBd3I dManeS mBBaDd aEendi nRse pfpratse mm=eaenaBdn30 RmBaiD mEED3s EaRnSn kBEYDb a prCrraeedn mBBSnoooonbmsan kokmeae mEsadd Eoaaann kBfeInn sEiede ffEiiraoescaases nEMaoio@nommeed mBWLiE EoBmDde aHEsSn fEBddD ad Bd pH wand Ed ED Es Er Bg GE amanSEE containTSAO! H-24768: Developmental Toricity Study in Rats ~ INDIVIDUAL FOOD CONSUMPTION (grams) GROUP III: 100 MG/KG/DAY fNroupER 1-20 DA2Y0S.21op GESTAeTaInON GSeassssa19 Gis4nsssz370 GGaissssaana GGaissssaasa sSaassssss07 ssiesssess ssiisssse7s2 Ssaisssse7re pSsraassessoens ScGaaassses6oo0sn3 n30s8 2sl8y a2ssa 83010 220ss a1ls0 2872 w2s 2a2 226033 2260 2zi2e7 320705 amlos 2z6o 3157s 2m0o6 2170s7 2681 mm3a zs4 3260 a wl 3sse sa26o38 nm2zo1 o2mz:sa n2l5s8 w06s makz 27 mh 2k DuPont-6515 ges not contain TSCAci -- Gio pompSen H-24768: DeveloToxpicimtyeStundytinaRalts DuPont6515 ~~ INDIVIDUAL 50D CONSUMPTION (grams) GROUP IV: 400 MG/KG/DAY aBELR as 68 80DAYS OF10G-E1S2TATION12-1 1416 16-16 sassasss2a3s Gsiassss3zze Greeasns pGarssesz siGsassssses Sisseo saGsissseersa G8eessss7770 GGiisess7e3 SSaaasssaasa Ssaasssseens prey u2z3 alo aasess a7 wasss as n1l.s9 als e20s 1a 2104.6 19s 2276a3 93 p2r6ss 271 w7i's 63 o5w.s2 wis wsls 13 2108ss 6s zuen las 2n.a8 es 1 2572 20 a3as als u9l1e ah asshs ies mllas als 212aa ass 32126sk a200l8 e a821 2al0s amless zalms mml2e 243s a19l0s7 21 a2l4o wiz 110h6 13 w10e7 20 2uas ow 11aa 26 a1l2ae so 22003% 20s a7s2h a2 esls221als alo es e1l5e7 164 a1es les s2als sole 220s 223 ssisn amslles a1l7ss osasslr s2l0s4 o2l0 ss als isis aa zz sed ale 2a as aslo -- 2s ms 1 2 2: ms 300 23 eo. Emp Ssaannittized Doss notcontTSaCiACn.. F-24768: Developmental TonicityStudy inRats ~~ INDIVIDUAL FOOD CONSUMPTION (grams) GROUP 1: 400 MG/KG/DAY aNnEoRn w20 D2AY0SmOF GESTAeTaION Gsaannssa2sz sGaa8nss2a6z GGaaa8ssa3ss pGranssz GGaaggssssse pGrasseo Gsaasssse7s0 SGaassse7sr GGaasssseess GSaasssseeen SGaasssseor 6Bl3 msas am0s xG3s a ao 118a7 BSolles 21as 1as2 a3s 1m5aa a20e2 9633 n1aa i1ses 2fe3e e2e1 t2oa 8a82 mm2s 11007 605 awss a1ns 226s6 227s 118h zzloo mwso a15a% awls ma wml 2106s DuPon6515 ~70- Company Santzed. DOT in recs cal H24768 Developmental Toxicity Sudy in Rats Dupont6515 APPENDIX D Individual Clinical Observations - Company Sanilizod. Does not contain Tscacal -- H24768: Developmental Toriciy Study in Rats DuPont6515 --~ Individual Clinical Observations Explanatory Notes Footnotes a The first observation recorded cach day is indicated by "a"; the second by "b". Observations were made twice dailyondays 6-20G.Ifno signs were observed during the study examinations,the "b entries are omitted from the printout. - `Company Saniized. Doesnot tcaontiainn TSCTSCA CB! -3 i 2g ti gsi sees 4 HEC J Bosal 8%s%% Tn --_ 2 got se tT" - - -- - : -- rs Sg ooBadi ddanli ooI onooon oonoo nn ' g gel <lll ll lolol: foGE3A: 8 8 5 5 os 8 os i 0% 3 i ggg 8g 58g 8s 3 ~8 i gf EER BB 8% 8 8 & gii 835 5 8 3% % oz 5 2 5 28 5d LETHE 9 8%58 #8 8 28 2d 2d 53 TF fo: o:oig `Company Sanilized. Does not contain TscAcBl ci i a i P53HE S JCS E S O gst... 88. BLD Tomo Pog ~ lg En cE EEOC I 0c : def Il loll g Pos 5 5 88 4 4% 5 3 3 3 | g iF 8% ;Ei 08404 s% 54 EOE OEE OE OG 8284 1 gi 5 3 35 5 3 z 8 3 z cf FOF EEEEOE :FoBOEE z EEEI EZ % 3 i 0%: fF 3 CompanySanitized. DoesnotcontainTSCA CBI : ii Bos POR aC mii oGaees = 8i Egsilf oigti i043 aan ; gi ogef eee ilnlnlo 5 g4f ( 2 = iPo sasaa os H1gd 2 ~ =3 SoesEfEiPi < ofp88 pgs ox 8 noi 23 SE5H8 E2 3 8 of i ompanySanted. Doss conan TSCACE! ~ 3: ii | i g0 cd JooESE El 2 OEE LDL AD eee Oooo Does 0 eee ~ LEE ks 2 gai DLT g gu ooo oTononnononnoroo B40 LC 0 lo alan od 8 i - . n Ta __ a" 2 4 J 3i H of , {egg Fst id 88 o@ 288.8:i%&8%& 8; :& $8E%i 5xExE5 5ZE[5xEE5 E[EGEREE8 OEE EBE EEEEEEEIREFEEEBE sfuhiigEigof: gt8g:tgdifogigidigHlgIgd CompanySanitized. Does not contain TSCA CBI 3 i ged Se CTT ts me nt pn) . a. . .". . . "ae - - Eddi ooo ok E gif 441 1 IIT nolo ' 3 Sonor Ef see + tee + ee =. 2I g J #43 & ams 3% 4% 7 3 wav 3 H | 4 ge gi 8 g Lf 28 BE gE OE EEE SEE SE 4 8% 2 8 f# 8 78 2 3 | oe 87; Ero: EE OEEEE 5 S81 <8 8 8 8 B88 8 8 :8 8 i SCF BEE BE OE SE EE BE KE ~ F sghiad dg pidogd p38 pd sd gd dg i E BRL F f F fF % i i CompanySantsd. Does notconanTSCACBI  2 i { gi owt aio goesidi ito Ji - } - 8 3 Eg3aip 0 fap Zi--- amalin oSo oo 0 P 8 EaEst i Geir r oT ilo g g Ebolieas ss 2 i| 4& ~ of = i i82 ssiiii fggif z8 :g 5% FB ids8mi{iggE8i2gs g EERIE 2 i Company`'sanitized.Doesnot contain Tara CR ~i i iz ii aBacll 80 i dT ae ie ddtdheS dslA iER en i i 8 831 0 ddnigEdsEsEs fi 0D oamlllEmanoaEiasl D0] , B4 0. LE: Asan oe 3 g Eopal c0 c oEdEnE idmmanso no e o oC & Bo4g1i -oc Tod dTiTTETEagAa ATTTT TTTIT I - T- o- - 8 ES co Essen fe Bogs 1 desdadiiiiiiiiironono f 3s smn on EOE or Thm ooo 2 i " a 545iKARARATAsAsARAE 5 5 5 3g jifee yiud 8 ii8ogd 3 [283 2 EN gf 2 1% 0| g21 f,i7 f2#F 3f8F 2s88 sz8 ez8 ifI2 T fi3o z8 8 i4%2 1i fgfiio:gogz: p3E25r32e3p83i88g4 oiz4 go:5so: H 5"8 i fEfE z Bs EsEsisEsisEas offfoEOafEi ol oCg ~- sgfigigi iid ddfdagdgig 5 81 3 I 3 $0: 3 CompanySanitized. Doesnotcontain TSCACBI ~ 3f% i i i 2 cccdgaede ceeecdpig B gi trast IR LRN LL... [NLLA - Eup Pog SIA coEEER Eo DllmEcomesel omen lldmmana Tn To = Eonel TUTTog 2 5S hriiiiiiiiiiin: Srscereeeas 3 Edi SaswalaLaliatiil onan g | FAGASASASAGASAREE sAasAacasasdd & 7 Pgf Beg 2 ozug 2g2 gJd sEF, pi8oi%iz EBrgRECdG8 BBeig;sa,g8oi8 3i $s8f i g3E28g38eEfZixggc iE. gpfeBRiIEsx4, 2& oF " 8 sas if siE sEssE Is3sE IsIiE fBCY EEE sELsEsIE aEIsEgSE tEIoOfE i 8 BEI E i i Company Sanitized. Does not contain TSCA CBI -3 i Jz ii a 8i 1 .- arene TT, . . SEp T LLIEI R WNTAYT, g5f 00 IIIT lmmmman lll LEED LD LIIID IID Dla g Ei .- EE cas . SRT =| E EE on Ek 8 Bai cc Tete ees sddeeesseesees g Bai D0 DITTO UID mdllIIIIIIIIIID | 2 aul WR g 0 F4f 10 IUITD TIT D IIITITITITIIIID 2 : as sands sas 5 FAGARAGAZARAEAS 2 3 8i] &3 d| d of i i 3 HA 3 38 2 iI 3 i? 2% gyi gE 2 $E2,1i E8F S2F1 8BO8E oBrpf:e.g,y.: GB| S 2& 8F i sv 5 % % FEEEaL] E a% s"88i3 8E8f 3E5E8F 3325 ! "s8g:s2s8a3:c2z.il4 oig uii pEiE iEgEEEiOiE:ioifddEiRiEEiEiEiEiEgG EERIE % i 3 Company Sanitized. Does not contain TSCA CBI 2 i dt TT oan pv BICC oom oun EB oggi cc cs TTR eee - 3OERD ee FORM. oe i; 3 oat oT oTooliiiiiioliino ' Egcihf 10min C - - - Sot So - Zz i 5 a a a Shiasan EERE] a Fosfiannnizigamg y i, if71%% 2:f,1% &5dig $z 8 E: l 8x 8ooBx :o8oz zo8ox :oygEhEEgzdsof2oz83Bo:&= i EE FEEE 85 ~ sggighaigi pid 13030 0 ELH I id CompanySanitized.Dossnot contain TSCA CBI z i Bai ad gf di dni oan gs: us 0 Eg god oa odio - E |E B dRdLl Egil gei Sain 2 iosasas q2 2 i -3 sz sii oefiEgB Si eld Caaigiid BEI: comp sn `Doesnot containTSCA' cal i | i gil FE RAE aE FH .. ce Rn. sense TURNS. fab DD EES lmsman TT andngens Lo BED EER wand m0 aaiddddd Pogo EESY EEE 0 Bal gn aT mmmaedmtete Hcg mans --~ 0 Ed 3BE ggeabb TT 1 iIiiiiiiiit gidendthees GoGcamea ttt nonin edssdssiiiocc 3 ? gash nonin SER 8 ga: " Sessa Cae g i 5a HASAsAcARAEAR SASAGAdAEAGARA 35: [iI og gL ig 8 &23 gEf8 5 WS 8 3 p5e:i0 or5 osgsEgugiiiiE:: B[fiiffe epil :gpS80 fBrf BsEoEsEsEsEsEd sBsRsEsEses g g cogfipfd Fai 3333338i 338334133 Ey [RE - i El i &| i gon gi snes 000 ee asd he Em 2 BARR Menenee +R, cfg Bal coiiiiiiiiioeeliiiooniiiiin ' 2 BSE TIIIIIIIIIIL LILI Will 2 ii SINIIiLIINNT ARIAL ONAL. g i GhAsdeacAansas sacdanw ihsbaas io2l 3 2 |gd 3I d| -~ 3 2 ii| iz 3g3 E58s3 3s3g Pf 1g, : Bei f geist eBf iia88 fd& srs Eig 3 3 sei, piEfiogEsn o. oO I8C 8 ii iSggs5 EEEE8 E Bgos Egg8y8E t gio f C8 aEElgi4 aidpdfig iisag iei 5 Z2i 3 3 3 CompanySntznd Doss ntcontin Te 1 Bai [llldlsAsRslgl (IIREIREIER gi5f ovoEdidaEdRadRalsl E ld ea dd sAe LBS Dla ldadedsdd 0 Tle ad ad EBaRl coiondiaciRadsnidaan0d aad daainaddaidididedd oBab gal d gi ed dd diId dd dodEd EE III - Bal sElmmsRlllllllll sell i Sat maa ET 3 Set tse rrsrrassssss tararesrsrrann 2 i HAGAdiAdAsAcAnAanas S4ddddsacAsasa 3: JH 3i H - 3a ii adi f0s 3EE% i. f5, i4 BEisEgi.Ez8 f5i% osf8f: f ofB s 28i 4i sBeBrEegEiEfcEggulEa;s 2 Fi8ai0c8th;l $81 sssssss55 sgsasis cgi gi ddd3diiidgdiiiigs g8 zHEEIi 3= i2 CompanySanltized. Doss not contain TSCA CBI 3 i gsi SCs Sst es Test 48 sd es 24 a Gn, SRLRR, Hatt ad aa gi HELE HE. BRE 2a sarin aaa Bll 33a Bil ET ds daisies --_ 2 ol Toot Tot gg TTT 5 Ce sino 3 edb iii g i fAdAasAasaa FeAsaean d4sisAcasased 3 7 dg ZI Cf3Jo; i i ER : ig 8: 0: Ezii fBfg #1E 2#2, 58 BoeEi8Ez:8 E3 $ ER54 i 8 E E Ea AEd nE8 d5 0 REES383E; HLEGE28 E f$2aiil3B38ig BEEiEIFfa RBIsaofEa aiIgfEPgRgIIaIgEIgENiHEa gE i i CompanySanitized.Doesnot containTSCA CBI 2 i ZU "ee "as PPI. a A, cy vu a af on dEEaEE ded 851 0 00 [llmmAmasmmss 8D EE g Bai dd ddqdd i Bi CCC TUT Aw TasTTTTTTUTU 8 Bai Cc TU ddagger = gsi 0 oLDosmsRliiIn = 3 Bed IID IID lllliiiiiiiiiiiiii i gai II eae a i Lo wy |3 iIFaE s Ai | gf3 J33 _ ot EI ogi E g 5i1 %3gg axE 88 2:x S88 3EK8 EEf&8giEx BEEE Ca 8;o 8 (i S<B8 E 8BE8E8 <EEE2B2E2R8E2L2E2 I8 G sgdipl agli AAEII RE3 | HEDE companySnitz. ossecon TSCACY -3 i g2 ii Bi (1100 IllRs ld mdRs Ed Rall $8} 11000 IsI msImsR iERINU Eqb CTU Toda tddmas tS 8 Bar CUCU ddTo4dad Toor --- 0 Est tt ogdtddddg lg Eda llllll edieedatiiiiiiiiiiiiiiii f i ai DIIIID TIIIIIIIIIIIIIIIIIIIIIILL | GEARAd GASASARAFAGASASASASAGARANA 4 ig os i iH Toy ike iPHE og2 8=g irig2 dE82 EEE 2 3=2 d1:o 8 fsiF1i og2Hp8Eg8sl5 iB8ip8ip::s f1(p3ifE, IDgRiiFdd] Poi Bai fiiEEEEsEiEEG i FH PEE EREIi REREER RARE RE Company Sanitized. Doesnot contain TSCA CBI -3 8 } i i gil LE EEE LE 2 uN. ca aT syn aea YL 28 df 0 sg llmmmmmmss TTT 80 g Bal co an Cte TITTIES To _ ggE Bal TC d H dd a Titi oo 5 z 3 FE pei Co IID Game TTT TIIIlIiiiIIiIiILL To ll ' oesi onniniiniiiiiiiinon BE gi "oe eter tteerrr enn "oe g i sas GAdAtOcAcAcAdAsAnAe a sas 435 Pi j ogg 82 gfEi8i, 85gf83 33 82,81 3g8iiEcE f Esp82o c8f82a:,o8s92 8x %8BF BgF 8 Z1| $EE2ib3i8gs T2iEeSl8E EeEiE ldL0 T= E4G 0x 2 $8 i828 sssbkeasgs id8 2 g g fesk cgi gid pddd3d3823838 33538 488f48 H 3 3 EEEi EF 3 Company Sanitized. Doesnotcontain Tsca car -1 2 } Bei 111110 lAdAsslllRssgAl 82f tt diada ms ff 8000 msslllEmEnlll LEED IIT Eddies mEiRi ggt t GdEmditEadeeEtiaoo oad Cg ddsiEde To - 8 ogi tc ddEiERT 8 Edl or ogggaege : EBA inno ddEdtioiiiin : edi inion 2 } dascas AFAR ARASASANAGAEAN g 3HN g4Z | 3 Cd| g i fo g ii <2 gz L2 rE45i14 2g 228 38 58E3s efi pfgf of fF ff gsi, 2% GE, BgEic:; $8; EzEf sgdaigsgil 2api i5S eBz % iaBiEiSiEieH iiE iRiE =d8 g Bi 3 3 CompanySanitized. Does not contain TSCA CBI ~ 3% i 2 i LI HR Bei Hgaoiw oz #oi J EEE ogl [aflEdadiEdlllmdl a1aa. 3a9ac8a Aa m maa aTawe - RR _RRARZ a= as gs sms sss 0 1d dded dead TTC Lc BommoamaAaR. gi ARoaEEmAL -- Fg OREM3i L cddG gedU antE iriR ieeL ees 48 a Bed DIIIIIIIIIIIIIIIIIIIL 8 Eal ciiiiiiiiiiiiiiiiiion- 2 i fAc4sdsasAcAsasacanan a Z i@ gs 3 3 j 2 8 22of$p1.g1 8TgEafuRzT :OF 2 Bi8dEB 3: 2s54ii ZFe8d4e8E $4F48.EE8;;% 3 $81 sssssgsgest i 4 BETEREEERE: 8 8 sii gd fii 333383348343i8 `Company Saniized. Does not conlain TSCAcal ~ 3: ii 8 i 85 8d llmssdsd III gsi os8 ims TT gai 89 ddd TTT HET og Teg 7 BEB adda ITD ETT Fai add a 4 gel nnn t EH Torres Tot CC g i fAdAcAeAshad a fAGAuAes EE 3 ii FI 3 I3 :3 Jf jamie iilIREARLA, iB 2 S_ R E: fI EfgE d[EfEE R Fxg E Eg4 1 gEi BfefpFg E s oxox ll Shi SERR3IF 4 2E gg zg pf FEEEzRgE EEEE OEE 5 341 32 $338 366248 388 z g iii 3 z Company Sanitized. Does not contain TSCA CBI H24768:Developmental Toxicity StiundRatys DuPont 6515 APPENDIX E Gross Postmortem Findings oo aniized. Dous nol contain TSCA CB! 24768; Developmental Toxicity Study in Rats _ Gross Postmortem Findings Explanatory Notes Footnotes a Pregnant by sain. Abbreviations N.AD ==NNooADbantormalities Detected Duponcsis --_----mmmmm 5 ge _oaeadD0ossarcana TSA F-24768; DevelopmentalToc Sdy in Rats Dupon6s15 - GROSS POSTMORTEM FINDINGS Grow 1: 0 ma/ka/day SAunmibmearl Dan code Structure(s saGisnsszyo 1s io SSiasnssaae 10 =I ssaassaasss 2i ppe= GGaasncsaas a5 ppee SGaannssssas 52 joeI GCiinnszeae i2 po= Cipnosreer 55 po= CGaannesrrs sasses ss5 5 .-=-- GSaasssseern EH7 == - pSarniceods a7s% pooI Ganeoz a . Pinding(s) wwon wwoo nnoo rWyo waoo anp> aa>> nYoo nJnoo xrwoyo wm Gomes" sant ea a1SAE acon' -- as. opm Toy sy nas fe - Gross zosmoRTEN FDINGS oBseEat ones snes rntinate aE pi = 5 E=E T------ GompSaEny H24768: Developmental Tosicy Sudy in Rats Dupont1s - GROSS POSTMORTEM FINDINGS Group II: 100 ma/ka/day Naunmibmearl Dan cose Structure (s) pssraes1ms 2F0S p--o SSsaiinaasssaaz0r i;3 ppjooo pisssraaesaas 3&3s o==s GsSiisensss5ss07 2i38 === SSssaaaaessse7es2s a@a j=ool sGpaarssesse9r iiacs == = GSSiianssesseoss &a 5 io=l = - GGaisaccoons a5 == Finding(s) aHD =ao wwwwwo Twwnoo wrAo>e wwoo wwweoo xwapn a> _ -- esace!n 00%! not 524768: DovclopmenTovey SynRas Durowsis - Gross posTHORTEM PINDINGS [-- aBnipEat meee snes FH capasossrcaeisi 5i. --== wffrroee aasaeesess $&: =i=on =ffprroeee Ga a saeinss 2533% ==== fpffrrosee CGioenssnens 535 === po-ree psapreess F@5"y ===i Fbb=Seo ~ Gfi seeaccees 3"52 ==== 8=ow - reerarson 5 "Compe eenseTM H-24765: Developmental Toxiky Sudy in Ras Dupont APPENDIX F Individual Reproductive Data gostaotcontain TSCACE\ mm H24768 Development Toy Sy in Ras _ Individual Reproductive Data Explanatory Notes Footnotes a Pregnant by stain. Abbreviations --- =No Data Duronesis or gwTTI DesonainTSOACE, ~% 2 2 geisIagaEIRTIEaTLRERIE i | ramernennesennnensenze Bl | gerenwanngagracasgoany i i Bloons = EHH BBRR || wi"triisiiiiitninininieiitiiimnnmiinegoyn EH BAl IwiEitEiiEiitR imiEigE imnM ingAl yok 3 | it | ssazzassssgszanzzzsaes 3 3s=r 2 2 28 Bf || zsaezsnnagvzvaannaannecnausuannsantennaysys 8 " 2 ERLE EER EH EE EE EEE Company Sanlzed. Doss notcontain TSCA CB :2 i 2295IRSRYRARATAILEARAT i |3 | ggrmeaeecmaegersgtaancerooaganer BY| wavanmansaennnnoaravn %g 2 ARTARITAARLARATRARTIAAN E 8 pbb bbL bbb IB HH : 2 g Z&R fBrEEsRsEasEmRmiEzRiEiinRaRnEtRiREnd G1 r00t0tmntttttatttntits Bl friiiimmniiiieiiinii uw 3 | ansnnsnnnsensnanansnsy zf 5g 22 f5e | sassszmaansnsazasases 2 iE | EEE `Company Saiized. Does no contain TSCA CEI 3 8 E| 35323333829 x33R838aAS Bi JE 3 | crosegononarnnnseanian 5 Sssngsnsnseansaggsaaan ~ | E : g 8 g | nnn i : 2 gl iiiiiiimilimii}] igBR tiiiinimmitigeiiniiig BE iitticimminnimiioinin 3i EBl iiitgaimniniininii}] HL i FgE =F | azzanzaszazanzzzazians 3 i : ie | sasassazansnsanaasanas z if | EE CompanySaniized.Does notcontain TSCACB! ~ 35 2 -3 88| yusssuzzaus ianessensss Ue i | FGHGRIRGGE | moemennunes jerensogeane E883aE|Rsrennmanenn :[veannenras t "2 5 Or ~ : gh nn :. i 5 sibbbb Ibn Eg8| PPil mia iil imi iilid teonmi eati iiantia ati il :5| Z2I FPElnaiiitiliavliln! stmmampeinmeitnimntiids 2 3 88| nengmsnunnn ingnzazangs 3 22 3 85| nnges ;, gfl 3 1 | RR3BBBseQang i2anQassees 8 8 . i ER AREEE HHHE EE `Company Sanitized. Does not contain TSCA CBI HL24768: Developmental Toxicity Stdy in Rats DuPon6515 APPENDIX G Individual Fetal Weights and Alterations --_-- ee "106- reTTTmecast! mpany Saniized- DOS F-24768: Developmental Toxicity Sudy in Rats _ Individual Fetal Weights and Alterations Explanatory Notes Dupont 6515 For caseofrecording, many ofthe findings have been abbreviated or coded, as listed below: a = arches) bil = bilateral cen = centrum or centra It = left n= NAD = lumbar No Abnormalities Detected no = right th = thoracic -- = NoDaw Subcutancous hemorrhage that was not present in utero. Renal papillary sizes refer to papillary development using the scheme of Woo and Hoar" Alterations are classed as: ~ N DV = = DNeovteelsopmental Variations VR = Variation due to Retarded Development M = Malformations Numbers are used to: Indicaterenal papillary size Identify specific stemebra + RefSpeecriftoysskkeulleltbaolnpeossiatcicoonrdfiorngritbosotrhevefroilclborwaing key: 1. Interparietal 2. Parietal 8. Squamosal 9. Tympanic annulus 3. Frontal 4 Nasal 10. Basioccipital 11. Exoccipital 5. Premaxilla 6. Maxilla 12. Supreoceipital 13. Hyoid 7. Zygoma - Tior- Company Sanilized. Does not contain TSCACB! H-24768: Developmental Toxicity Study in Rats Dupont6515 _ Individual Fetal Weights and Alterations Explanatory Notes (Continued) Due to technical errors that occurred during the skeletal processing step, the following list of fetuses were damaged during the evisceration process and the listed bones were unavailable for examination: Group I: 0 mg/kg/day Dam 648553 Fetus 13 Rib 121t Group II: 50 mg/kg/day Dam 648600 Fetus 7 Rib lt Group III: 100 mg/kg/day Dam 648599 Fetus 7 Dam 648599 Fetus 7 Dam 648599 Fetus 9 Dam 648519 Fetus 3 Dam 648594 Fetus 3 Humerus It Carpals bil Carpals it Rib~ 121t Stemebra ~ 4,6 Group IV: 400 mg/kg/day Dam 648539 Fetus 5 Carpal bil Dam 648539 Fetus 5 Scapula rt --- Dam 648523 Fetus 15 Rib- 121t Dam 648540 Fetus 7 Rib~9, 10rt Dam 648552 Fetus 4 Rib~th4, 5rt Dam 648570 Fetus 12 Stemebra ~ 6 Dam 648577 Fetus 13 Rib th 8rt Dueto technical errors that occurred during the skeletal processing step, the following skeletal specimens were disarticulated and thus, were unavailable for examination: Growpl ~~ DamNo.648553 Fetuses No.5, 6,and 11 Growpll ~~ DamNo.648537 Fetuses I-17 Group DamNo.648599 Fetus 8 GroupIV DamNo.648539 Fetuses 6-9 and 11-14 Sanitized. OOS,notcontain TSCA cat Ts 24768: Developmental Toxicity StudyinRats DuPont6515 - INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP I: MG/KG/DAY FDEATYUSK0.Wo/. _perus wr. _sTRucroRe Foomics) cuasstercaTIOn caes3i? 2 S5.a39 san vertebra a3 5 s5i.n87 S80 Kidney : S57 skit 76 S6.a2s8 san vertebra 105 n sSaans Slo vserxtebra RRweewttaarrddeeddooasssiiffiiccaattiioonn (bil) VR a(cen eno) w RSwneoatialzdapdapoilslsaifi-csaitzieon2 (rt) WR Rweot@a.r1d2e:d2,O6s,s7i0tii1c)ation w RetTa,ere1dn2e:dt2h,aG6ta,)s0i4f1i)cation w= = wRReenttaarrddeedd Oossssiiffiiccaattiioonn (661) VR cen 1) w ces7z0 2 s5.3 a 5 S31 vertebra - .:5 i5si.ss0s8 .5 s512ie 1105 Si55ls2i stemnebra 132 1 5s15e3 siz 6i 5l5e2 wwww Retarded ossification wo{een tn13) = fwyo ffyy Mwwiowsaligned (1,3) ov wwww wopy wo Company Sanitized. Does not contain TSCA CB! BCH H-24768: Developmental Toicity Study in Rats DuPont6515 - INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP 1: 0 MG/KG/DAY oFEnTUwS0.KO/. FETUS Wr. STRUCTURE PIVOTING(5) cuasstricaTION 6eeHds20 (cont)5.67 Kidney papilla - Size 3 (right) w sess1az 5.65 23 a 5sl3e2s mb saa 5s3 sailsse siz 85 sl5e0s vertebra 0n s.s2i2e 152 ssllsa mwon Supernuserary (short 13bil) DV SnAoD Ary> nRe>tarded ossification (cen th12) w aAApDD EY seesT20 5.47 vertebra 25 sHe az --- 35 spe e ` sis 7s esiratn 105 ssie o Rib 1n2 s5li2o0 un Sao vertebra 1 5.70 vertebra Ret(aerednedth1o2s)sification wr nNApD aNDa ray> wSurpernumerary (site 141%) wv w0D oReytarded Ossitication Ret(acrednedthiOss)sification w (cen th10,13) w Company Sanilized. Doss not contain TSCA CB TTo- 24768: DevelopmentalTricity Studyin Rats Dupont6515 - INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP 1: 0 Ma/KG/DAY DFEuTUSvo.30. _reros wr. _staverone Promos) cussterearion cas7:as 5.0o0e 00 3i: SSoi oor 0Ino :;: HLaEah wnnooo te5 bit ifh6se necooo i3un 5 on5 ncoo no ses3:a6 s$8m sen :3 5$.237 SiSamnnaeiynie --- :s 55.5056 aSnaatsmie - sae vertebra s5 as557 0 23 Swantamie n3 S5.i2 Smaaatsie n sm wReotGaoxbdie,a o6s1s0)ification w RSpaeepttiaalrrlddaee'dd`OOSnniasziietciicc3aatt(iibooinnl) ((b2i.l6)041) V=VAR ReReeyttaarrddeedd oOsmsaiiftiiccaattiioonn (bil) WR RetGa6r.d7e,d005o0s)sification = awnocen et) = RReettraarriddeesddeOonrsas.iiffsiiocciaahtt)iioonn (41) VR = wRReeottaarrddeedd Oorsasiitfiiccaactiioonn B41) wR ws(7.s1t hid) w " snotcontain TSCA on CompanySanitized. Doc: Te 524768: Developmen Tsisty StundRtys Dupons1s - INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS aroun 1. worms oBwrowto's. sores wr. _smmocrume enmmsts) cussrrrenrion suas33en 5S.E50 ventana wReobEasaees )osssication = > 552 vertabna `: sBoE wTm een rsReeutEp(oaeccreiaanmeensmaetbcr)astssylseciiactatteiioonn1 w3 . sso sTeennner RRoetf(aazrreadneesstneOormsssiiteiiccaittiioonn (1) w , saz sGemrveebea ErafgEEirtaleeat )]oSnlbeieta>tiooann) == w . se sTeornmebra rpeterireens Sraesscescatnion (@1 = i$s oSnE verterna n sa wRSeosbp(aeecredmneusmoerornstsyscs(csaittieon20) n0w Tercera ~ 3u 5.2i6E venena wResaEvis.torsteiearion is Retacded onssscation PB 5.56 vertebra RettEaerndedEtnioan)ssscation w = saas1:3es "5iwnn wnwoee ::: iiiEan wwweee - Company SaniDioszs oetcdon.t in SCAG: TE 124768: Developmental TonciyStudy inRats DuPon6515 - INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP 1: 0 MO/KG/DAY oPaTswo.Wo/. pervs wr. _saveruRe roms) cuassteraTion Gee0se (cont)5.30 s5 55.5573 1F0e iseiss 1132 s513 is 1 Siz vertebra vertebra Retcaerndedthaozs)sification w xa aww mwoo Ret(aerednednaozs)sification ww cios1ss 3 5G.l9a mip a55 SSsis lleo mp :7 sSiha o5 slSelse 1120 sSSiinsz idney - 113 SSs3e2 sKikdniey w>Suopernuserary (site Lert) ov >Sopernumerary (site 14 xt) DV FEyy wFoy xPapilla - Size 3 (bil) ww ISReeoatla)rdepdapOisllsaiti-caStizieon2 (2(1b)il) WVRR 23 5s.i69 a5 sSllae stun 5: Sseisa sam 7. 5i.56 san wwoo wRewtarded ossification (2,6bi1) VR oReptarded ossification wReot(a6r.7d,ede0io0s)sification (bil) w VR `CompanySanitized.Does otnotcontain TSCACB! ims H24768: Developmental Tonic Sdy inRats Dupont6515 ~ INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS Grou 1: 0 va/Ka/oAY oTwontuwso.wb. remus wr, _smeveroms emo 5) cunssrereation cass cone.) Vertenra Reteaorndedehiooscsiini)cation = iit5 ispnea wwweoe i3i iioans jwWlww bi3y issao wwwooo Wn on wo T ss vertebra 2 sas vertebra 5: s$a5 verona s sss verteora ~~ . se vertebra - Pe 10:5 HbHied i HE -- F23B] sTHi ia j-- RReett(aoerrodaneedamrooiesias2ii3ti)iccaattiioonn = wReov(eeornedenoas)sitscation = Rot(eaoornnaeatthhoeiiasti)fication = = Rweotoarndedononisitication = wwnooo Rweoteaesndedthoasysiication = nReoty arded o ossification = _ o Company Sanitized. Does not contain TscA car Te 124768: DevelopmentalToxiit SuidnRayts Dupont6515 - INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUR 1: 0 MG/KG/DAY oFwEeTUwSoW.o. _rerus wr. _sreveroRs Frm(5) cuasstricaTION ssas3es a7 vertebra 23i 5pV.ee6d 5:5 i5ill1ss0 : 16 verter 1105 pi54e.3259 sternebra 11i23 ppujett 115 iass cans3er z 5p.9t0 Kidney ~~ 3i5 S5oosn :3: SsSlolloe 115 sSol1so b3un SSsolneo xine can3: s 5&.30 Ret(acsednedmios)sitication = aaann nnnooo Ret(acrednedemots)sification w 1nRe0otasdea ossiticacion (6) = 0nwoo wnoe Swweooal) maptlla - Size 2 BAD WR wwnooo nnnooo ninnooo Spasal papilla - size 2 B41 WR wwoo Company SaniDoissnzotecodnta.inTscACEI ise H-24768: DeveloTonpicimtyeStnadytinaRalts DuPont6515 - INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP 1: 0 MG/KG/DAY DFEaTUSwo.0/. FETUS Wr. STRUCTURE rvoING (5) cuasstecaTION sas33s7 (cont)55.783 Kidney 5` 5sl7e6s ski 57 66..3080 05 sais z a2 5s.a7r9 NpaDpilla - size 3 (it) w Rxeotarded Ossiication a(@bilsere) w 830 8NN0oD sas1sm 5.41 2 563 vertebra 3i s5i.5z8 5c o57m3 57 s5i7366 Kidney 05 5si7m ~ 12 ssiarr mip 5 sis aReotarded ossification ap(cen thiz) = uNDD ppraepyilla - size 3 (xt) w anDD awpD wSubpexnunerary (site 14xt) ov seas776 5.52 23 sl51s50 Kidney i ses RSkiub s 4.63 vertebra 53 5S.i8r7 waPa>npilla - size 3 (bil) w SRueptearrnduemdeorsasriyfi(csaittieon141(te)lt) oVvR Ret(acrodnedthiods)sification w axan CompanySanitized.Doesnot contain TSCA CBI The H:24768: DeveloTopxiimtyeSundytinaRalts DuPont6515 -- INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP I: 0 MG/KO/DAY oFEaTUSO.0/. _eeTus wr. sTRucTURS NDING (5) cuasstrcaTION 6485576 (Cont.)534 vesrkteabra 5 5.62 vertebra 10 5.45 vertebra n 5.85 vertebra 12 5.85 vertebra 5 5.44 Rib RReettaarrddeeddOossssiifiiccaattiioonn (6x8) VR Ret(acrednedthiozs)sification w Ret(acrednedthiO2s)sification (eon thi1) = w Ret(aerednedthiO1s)sification w SReutp(aecrrednneudtsheaOrlas)rsyiic(saittieon1bil) wDV sass1ez : 2539220 vertensa aa 5a7m 55 ssiison s5 55..0725 - 105 aslis0s n S28 xidney 132 sS1e2 Kidney Rwewtarded Ossiication Teen' th11,12) w wwow wxo wwon . awoD Dapilla - size 3 (bil) w SNAmDa,ll papilla - Size 2 BAD) VR Gess167 5.20 h23 8s0s7 ser $75 ssSlimsso aw xwo rryy Supernumerary (site bi) OV wwow Company Sanitized. Does not contain TSCA CBI ns H-24768: Developmental ToxicityStudy inRats DuPont-6515 - INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP 1: 0 MO/XG/oRY oFEnTUNS0.0/. _ETUS WT. STRUCTURE noms) cuasstpicaTion s4ssa87 (cont)5.43 05 5s.i5a4n 11 s3s5s 1u 5s.5v1 vertebra Kidney Rviebrtenra Ret(acrednedth1o3s-s1i3f)ication w pASauDppielrlnaume- rSairzye (3sit(ert)141t) ww ov Rettaerednedth1o2s)sification = naaDp cess1es 5.47 Kidney 25 sGl es Kidney 35 s52o2s Kidney `7 s5s3s5 Kidney o5 sals a ssiie SAmDall papilla - Size 2 (bil) VR SAmDall papilla - Size 2 (bil) VR APaDpilla - size 3 (t) w ApaDpilla - size 3 (Qt) w naDD nD sasss2 23 ssiie9 i3 5sa7z s7 553355 svekratlenra 8H 55.278 skal 1n0 siamn wroy rayn RReettaarrddeedd oossssiiffiiccaattiioonn (6b11) (con ths,11,12) VR ww R>etarded Ogsification (2,651) VR AwaDn Company Sanitiized, zed:Doesnot contain TSCA cel Tiss F-24768: Developmental Toxicity Study in Rats DuPon-6515 --- INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP 1: 0 MG/KG/DAY FoEwTtUSNo.W/O. _rerus wr. _sTRucTuRe Pom (5) cursstrIcaTION 6482592 (Cont..) 5.50 vertebra in 5s.a2n7 Ret(aerednedth1O1s)sification w NapD' sens1or 5.42 32 sSsloi kidney 35 5si.s05 :5 ssilas 55 5554572 Kidney 10 505 skull 1n 55.5226 skal be1] s5:a22 stemebra N0D, Seall papilla - size 2 (bil) VR nwoD xx nPaopilla - size 3 (it) w Ret(aerbdie1;d12O)ssification w Rweotarded Ossification (6bil) VR wMiDsaligned (4) w sea1 s 5.07 - 32 Ssi2e8 shan 5 52 vertebra `5 s5.s2s9 vserktebra s2 s5i.a50 05 ssilsa sel Rweotarded Ossification (241) WR >Rettaerednedchiots)sification w= Rweot'arded Ossification (616) VR Ret(aerodnedth1O2s)sification w a0> AReDtarded ossification (2b) VR Company Sanitized, Doss not contain TSCA CBI Ti H-24768:Developmental Toxicity StiunRdatys DuPont6515 - INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP I: MG/KG/DAY DFEaTUSNo.W/o. Fetus wr. _sTRucToRe F1pNG(5) cuasstercaTion sass02 (conc) vertebra fr1} i5.s2s8 15 5s3m i1s ssiia3s0 Ret(acrednedthOis1,s1i2t)ication ww a0o wbyD w0o ~ Company Sanltized. Doesnot con.tain TSCA CB \ Ti20- H-24768: Developmental Toxicity Study in Rats DuPont-6515 -~ INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP 11: 50 MO/XG/DAY DFaEnTUSxo8.0/. FETS WI. STRUCTURE FTG 5) cuasstrrcaTion sess11s 5.56 vertebra 32 sssl Taaniuls s` s5.n06 7& ssis os H8 5s3e8 10 a Ret(acrednedthoios)sification w= wIeopertorate Fil(awnietnhtohuesmorrhagic tissue) Naap aADD NaDD NAD pr1e 5.2 32 s5.o59 53 55.0909 7s 5s5s3s9 Kidney 5s sslaa = 110 pse iz 152 ssiisst p1rs} il5e67 xidney k1d sisies nnaon nNDa NaAD Snall papilla - Size 2 6) VR aanD xaDn ANADD APaDpilla - Size 3 (bil) w waaDp Gess1as 5.6 wo 25 sHies wwDD h sie wD CompanySanitized.Doesnot containTSCA CBI Tie 124765 DevlTooxicpSamdlyeinRnts Duenss15 - INDIVIOUAL FETAL WEIGHTS (grans) AND ALTERATIONS amore 11: 50 We/RO/oRY oFowrvooss. sews wr. _smmocrone enone) cusssreionion s: ----i5h3 5 pe wwwooo =:5 ia3n5 wwwooo 53 sisinae wwwooo i Bed wo cas3: a 5p . -- Vertevsa wRReeobtaasrcdeedd oosnssiiciiccaattiioonn (2 bl) WR s: 5SE.50 vererra wRestfaxoendto)ssification = pr) = s:5 s3ia3s san wRnesokasded ossification (2 bil) WR - =:5 p55x ae 3 Bd wSwlspernunerary hore i) ov wo sua: s 5510 wwoo 5:: se3ne : pee wwwooo wo 5:5 Saaon wwwooo = san wo Company Sanitized Doatscosnidn TSCACE EER H-24768: Developmental ToricityStudy inRats DuPont-6515 --- INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP 11: 50 MG/KG/DAY oFEaTUSN0.0/. FETUS WE. STRUCTURE FmoNG(5) cusstercation 6481537 (cont)1.86 wo fo12 s3i0 nkDg fr1}s sslios oay> ine islso 0a> sass1as 5.67 2 Slee Vsekratlebra 33 si6.e020 5s 5si7e7 Kidney 75 sSi8s6 ski 105 iiissss sem 1 5.29 Sternebra - Fe12 553708 4 78 wReotarded Ossification (bi) VR Ret(acrednedthO1s1,s1i2f)ication ww aA>D S>mall papilla - size 2 16) WR xReotarded ossification (bi) VR IRetarded ossification (3b) VR RAe>tarded ossification (6) w >an Eg sass7ar 4.74 Kidney 25 ialmes `5 i5.l2s5 `7 55..2240 o5 sla4 0 is aPabpilla - size 3 (bil) w= aI> >> 0>0 uwDD Gompany Sanltized. Does not cort!ain TSCACBI Tie H-24768: Developmental ToxicityStudyinRats DuPont6515 - INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP 1: 50 MG/KG/DAY oPnEtTSwo.N/o. _eeTus Wr. STRUCTURE From (5) cuasstricaTION ses7san (cont)1.99 2 ils nnwD n3u i3n2 rkyy Gess1ez 5.37 25 slSiess i: 5si3s1 `5 iSles 1085 s5s0a3s5 Kidney 11 s5ilsos Fptry] s5is 37 i1s 550365 Kveirdtneebyra uw 5.90 Kidney aao aNAnD wwDD wwDo Snall papilla - size 2 (B11) WR wwDo wAn> ASDe,all papilla - size 1 bi} VR Ret(acrednedhO1s0,s1i1f)ication w papilla - Size 3 (bil) wr sass21as 5l.o6 3a 55074 xidney 5 isa VKeirdtneebyra s7 5s.i2e 55 ssesss 0 50 n>ao Papilla - size 3 (bil) w hSRmexatlalrdevdapiOlslsaifi-caStiizoen2 (bil) VR mo(een th1z) w nhDe nnDD Company Sanitized. Does not contain TSCA CBI Ties 24768: Developmental ToxicityStudy inRats Dupont6s1s -- INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP 11: 50 /XG/DRY oFTwUSwo.No). revs wr. _sTaveroms eno 5) cunsserention ft --S71 xiney Papiila - size 3 (541) = saozs3er sa6r : HEE --, ` sm vertebra s: sDa6e SKeirdeneebyra -:5 sHSueshe Kidney mn 1i SDe5s F3iS H5aEe --" ii SD330 aTeena Rwweootarded ossification Ret{eaeorandnedesnhioizst)si1af)ication w w Rseabp(aieriodineaachaozSa,sii1z0ze)iscataiovn = w wSsuaopielrmpmaepriadriya sized Qo (site bil) Va OV nSispernumerary (site 1410) ov nSfooell papilla - size 2 BD) WR SReibpGaeerrednneudnoenaronaa)rsyiti(csaitteion1010) ov -- casi7s: asah :i3 sSoi ea :5: 5Soi 8a 31S i SSiE Sxieaanrey 33 i bed wwwooo wJnoorod nFwaoopilla - size 3 zt) w 2wReofazded ossification (7b VR wo CompanySanitized. Does notconteiln TSCACBI Tine H-24768: Developmental Tocity Study in Rats DuPon-6515 --- INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP 11: 50 MG/KG/DAY DFAEMTUS0.0/. FETUS Wr. STRUCTURE FinpmvG(s) cuasstpicaTIon Gaass) (cont)5.10 15 4% vertebra wReottaerednedthots)sification w cans7ez 5.55 Kidney 23 5s7a i5 Ssis 65 ska s7 s5a7 san 85 sSi4s1 vertebra 1u0 5S.5610 Kidney Vertenra pXaRpDilla - size 3 (rt) w wReotarded Ossification (bil) VR BRestarded Ossification (bil) VR >a Retarded ossification a.Teen thiz) w= PReatpairldlead- oSsisziefic3 at(iboiln) w teen thal) w pr1e 5.09 23 5a4sss sKiwdunmey -~ H5 ssseos .7 sSis is s5 ssliees 110 ssiisa Fo2 ssie as 11s s5i9e 16 ss wSRmeoatlalrdeFdapiolsisaifi-caStiizoen2 (2 b0)il) VWRR >a> xxa0n xx0D xxa0n 0wo anDD AD Company Sanitized. Doos not contain TSCA CBI 2% 1.24768: DevelopmentalToxicity StiunRdatys DuPont6515 - INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP 11: 50 MG/KG/DAY oFEaTUwSo.N/O. FETUS WI. STRUCTURE FDIS (5) cuasstricaTION aeas1es 5.62 vertebra 25 5s.i0s2 3: : 3s3i7s $7 swan 50 slHees 05 25.229 sn un 5.03 Ret(aerednedtiOdss)i ication = uoDy nxADD Retarded ossification (611) VR aa>p aReDt(a2r1deesedniOls)sitication w op sees1ns 2 s6l.e2s0 3i 5 ssisn G35 xidney :2 5 pseits 820 verteora - 105 5s.s3o9 F1H] Fe] s5l7o alse po pe AwaD wnDD Saati papilla - Size 2 (Bi VR N0D Retarded ossification wap{een th13,12) ww nrDy nooo by sass17s 5.04 vertebra 2 5.35 vertebra Ret(acrednedthioos)sification w Ret(acrednedth1O1s-s1i3f)ication w Company Sanitized Do"1snotcontainTSCAcs ge = H24768. Devlopmentl Toxicity SdinRyats Dupont ~ SNDIVIOUAL FETAL WEIGHTS (grams) AND ALTERATIONS Grown 53: 30w/aont oPoES0.i/b. seus wr. _smavcne ens) cussions P} --bes vertebra Retfarodedthaoosrs1isf)ication - ` Go vertebra s sas vertebra RReotEEtarodrteesd eobpo]es)iiFthiocaattiioonn w . 5 vertebra - sa vertebra RReettoeaarrnnddeeddstheaooeoranressiii)aHt)hiocsattiioonn = w . 533 vertenrs :5 sPaB sen wReoteosaen d opetFhoation ww Ftarded ossiication pi) ln u sa verona RFeetteaarrndeeeddhsSooovrrsiiiatt)iicoamttiioonn = 529 vestensa ReteeaarnndedtsheSacsis)ai)tication w us --Sebrena R supSernme amtehnai)e ry (st ite 1x5) BY - w sa vercebra = 55 vertebra RReottSaaastniieodnthSSeaibboiits)iiccaastiioonn w teh w can33 s E Po w wpeormmerary (site nil) bv :i3 oBFiHr wwaoop : Be3 xan BWoR papiina sizes 0 wm snot contain SOAP! Bra & pany Saniized:0 24765:DevelopmentalTosicky Sy inRas Duronss1s - CADEVEDUAL FETAL WEIGHTS (grans) AND ALTERATIONS aroun 13+ 50 wo/KO/BRY oBaSwGo.. pervswr._smveruns fre -- pr-- 5 50 ~eh - i3 iie [B3EIT.Se 313 iussas s sao Kidney 5:$ aERe HE i33g uu5ae ==wo ppapiratShtae 3 xt) w= -3SenetCESS 2 == ha w :33 Fi1a2E. ::: fFouih $: i -- wFAoSrmunerary (site Labi) ov E==Y B300 rap-stizet2iGai) Teme tain TSCA CB' 124768: Developmental Toxicity Study in Rats DuPont-6515 --- INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP 11: 50 WO/KG/ORY oFEsTSv0.0/. revs wr. _severume FnonGE) cunssrrrearron sigbysyon cone.)5o0n fny aHhE J-- wwwooo Ret(aeredneden1ots)sification w ses?ss s.o0 VKeiratneebyza 2 5.76 vertebra 5 s.50 vertebra `:: 5S$.25E2 Vrearosneebyra .: 5S.17570 VKeirdtneenyca s S01 vertenca = 0 6.00 vertenca n sen VKeirdtneebyra 2 5.20 vertebra n s.20 suss3:ss spemt : $57 wianey SRmeat(lac)rednepdaenpiioalals1ai3t)i-castiizoen2 (il) WR = RReettcaaexrnddeeddnOiosss)ssiiffiiccaattiioonn = wPaopcielnlaar- ts,iz13e) 3 (bil) w= w= RseatpTaierieldnaedta1o3ss)isziefic3at(iboinl) ww RReettTaaerreddneedduroGasa)ssiiffiiccaattiioonn w RetcGaeerenndedn13ro,is11si2af))ication w w RPeatpTaieireldnaeda-1otss)isziefic3at(iboinl) = w aRet(acrendedtatOap)sitication w w0Smoall papilla - Size 2 BAD W - aot contain TSCA a Gompany sSeaninitize0d. T0- H-24768: DeveloToxpicimtyeStundytinaRalts DuPont6515. -- INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP 11: 50 MG/KG/DAY oFmEeTUSwo.NO/. FETUS WI. STRUCTURE F1voTNG(5) cusstrcaTIon sessss (cont) vertebra s5 S5.6750 vertebra s sas Vsekratlebra kl 5.21 vertebra 5 470 vertebra 5 5.21 vertebra 01 5S.640 Mares vertebra Ft1]2 55.0485 Kidney nu 547 vertebra Ret(acrednedtho1s1,s1i2f)ication ww wRewtarded ossification Ret{acrednedtn1O0s)sification (6b) wVR Ret(acrednedthOis2s)ification w Ret(acrednedtn1O2s)sification w Rettaerednedth1O2s)sification w Ret(aerednedthaOts)sification = IMa)lformation Ret(anradzeids Oastsriesfiiac,atiboinl) I)(cen that az) ww PRaeptialrldaed-Osssiizefic3at(iboinl) w (cen that) w - sass100 5.45 32 sslise 5a 5s2o7z 7` ssiize 5 e5.t20 1n0 sS7m0 oKrindney 2 Sls Rib >> nA>> xx wwDD wSuDpernuserary (site 141t) ov sSuepaelrnuPmaeprialrlya-(sSiitzee142bi(lb)il) VDRV Bis CompanySanitized.DoesnotcontainTSCA CBI H-24768: Developmental Toxicity StudyinRats DuPon6515 -- INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP III: 100 MG/KG/DAY oFnEtTUSw0.0/. FETUS Wr. STRUCTURE FID (5) cusstricaTion ass1is 5.8 2 ea vesrktaebra 33 55..6802 vKeirdtneenyra s5 86.0272 7 8s0n 105 ssiise 112 553160 xRe0tarded Ossification (2 bil) VR Ret(acrednedthOis)sification w Rpaeptialrldaed - OSsisziefic3 at(iboiln) wr a>(cen thio) ww N>AD xwD nxwaDD sass121 ss 23 5552591 vertebra " 5.82 vertebra --~ s5 55.086 3 sis vKeirdtneebyra .5 45.:3306 vertebra 0a 45.55363 vertebra 25 52.6407 i ik aw ewyo Ret(acrednedtOhsis,i12f)ication w Ret(acrendedtOhisos)i fication w 0ns Rpaeptialrldaed-Ossisziefic3atiito)n w wo(cen th10) w Ret(acrendetdh3,os1s1i)fication w NReatparded ossification wp(cen th10-12) w nSuDpermumerary (short 13bi1) DV Company Sanitized, Does not contain TSCA CB! HCN H24768: DeveloTospicmtyeStnadytinaRalts DuPon6515 -- INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP 111: 100 MG/KG/DAY oFEwTUSvo0s. remuswr. _stavcrons Promos) cunssrerention sesz1 (cont) 1is soanr aans3:ar spearzt i:3 oSohih :5. 5DS5585 fe5 1S5R Fwbey sKSieadanmney vertenra aso:s3a0 isEe aw 5:: 2i57n wianey - :5 SSiiee 1:5 soseah iF3S s2H5ee san3:sa sH.sE0 J-- 3: 5i.2e0 eRSeeit)paerrdmemderoasrsyifi(csahtoireon13(5b0i)l) WDRV wnnooo nhReootarded ossification (61) WR RaSeaofpairldieaa-oSssiizfeiscat(iboidn) (bil) =VR Ret(acrednedetoas)sification = wSfeuoypernumerary (site 1416) ov wTaopiila - size 3 (rr) w e5wyo 0r1e0y nSuopernumerary (site 1art) ov wReotarded ossiticatton wwoo(cen ears) w Gompany Sanized. Dass not contaainin TSCACE Te HL24768 Developmen TxikyStudy in Rat Duronasis -- INDIVIDUAL FETAL WBIGHTS (rans) AYD ALTERATIONS aroun 111. 100 o/kc/RY of nvos oe roms: cusssirroation can:} s (cone)LSaE vera Pwaordes custtication }:) ii510nk wJwoorsdtents? w iii 1i[a3a =ifd iu3 uvisee wo2y suns}?es 3 Hi0En9 idney IFseyatd op-isitze 2iBaA ::: $ iiT3sgB xia =B=ER vapsiizte2tGia = i:; 3ia8n xine FS"SER ap-isitze2iGa1) --_ HK8i1 i$15.n0509 sen own Tertiona RRiR0 eoebtfaaurisaeeeaddomosussitisiccaattiiioonn (2 (2 bil) 512) enti w sss?ses Seafrseaor oramer MaEltorEmacioRn e ven jWreare wjor Greater SepirtaelTeDeemteercitcuter) " 2 cos tionary =seall pap-siizle2lGa4) pe CompanySantzed. Doosno contain Ts cay H:24768: DeveloToxpicimtyeStundytinaRalts DuPont6515 _ INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP IIL: 100 MG/KG/DAY FDEaTtU0S.NO/. FBTUS WI. STRUCTURE FowIG(5) cuasstercaTon sess3is (cont)5.61 Kidney 5i 5s56s1 Kidney 7 ssisnt 5. sSleze n1 Bsiesrar 112 5si5s2i u 506 sess1ss 5.5 2 815 vertenra H5 p5e.t9e1 5 05 vertebra s 5.6 vertebra -- s7 504905 vertebra 105 s5.a73 n 57 vKeirdtneebyra 2 6.39 vertebra i1 s5.s8a >Snall papilla - size 2 (41) VR NPaabpilla - size 3 (bil) w wrwyoo NsAuDp.ernumerary (site laxt) ov >aD ES Rweotarded ossification 1p(cen th10) w wReDtarded ossification Ret((acereenndedtcOhh1s100s),i1f2i)cation ww wr R0etarded ossification 0(cen th10,11) w RNPaeDptialrldaed-OSsisizfeic3at(iboiln) w Ret(acrednedthiOss)sification ww oo(cen th10-12) w wo CompanySanitized. Does not contain TSCA CE: -_-- 1 H:24768: DeveloTospicmtyeStnudytinaRalts Duponces1s -- INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS Grove 131: 100 M/K/oAY oFEaTU0S .Wo. _peTus wr. _ sauce sommes) cussion caa:s3so ssia mn nsubpernumerary (site 151) Dv :i3 ss54aess wwhooo :5: s2S5ie5 ewwyoo i15 5oS5si a verterna bRSeiytpaerrdmeudseroasrsyifi(csaittieon1416) ov 132 iaar wwooGen tan) = 1ii iy3se5 wwwooo 3 se wo cas:7 s 05.%20 san 5 ie wnReootarded ossification (2 bil) WR - :: Us55 axiuaney . ars Rib SwPuaoppeirllnaume-rasriyze (3sitGet)13 bil) OY Swpermunerary (site 13 16) bv :, splro San nwReootarded ossification (3 BL) WA 05 UieaeSka SRweiotpaerrdneudmeOrsaariyei(csaittieon1m(2)511) VoAv 2u4n) Tpseoe wwwwoo i pid wo ----Te-- e CompanySanitized.-- Does nT ot containD sca car 2H:27476%8:DeDveveellooppmmeennttaallTTooseiciitySSwuddyyiinnRRaattss DDuuPbonot6i51s5 -- INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP 111: 100 MG/KG/DAY IoFEEwTTUSSwNoNo,O..FEFETTUUSSWWTI.. STSRTURUCCTTUURREE PPDrDvIomNNOG((SS)) CLcAuSasSsItFeIrCCAaTTIIOONN 668is557 (cont. 417 Kidney Rib SSruaplelrnupmaeprialrlya -(sSiitzee1311tB)41) wwRv se1ss 2.8 a> 23 a4l3es0 vertebra wReotardedOssification .5 siss mo(cen th1113) w wp 37 sen Retarded ossification (2541) VR sens1es 5.59 Kidney Rib SSmuaplelrnupmaeprialrlya -(sSitieze1421t()bi) VwvR vertebra 2 532 san Ret(acrendedthOisos,1i3f)ication Retarded Ossification (bill VwR s5 5558584 VKeirdtneebyra RPeatpailrldaed - osSsiizfeic3at(i1o6)n w s` sl5.e3s5 Kidney sea(clen pathpii2l)la wo - Size 2 (bi1) wVR - 7 s5i0e7 skal 5 5.43 xReotarded nD Ossitication (11) VR 1n0 ssiiss 2 sa >a> a 5 550 Kidney Seall papilla - Size 1 (xt) WR sens1es 5.56 2 sles w>o 34 5s5l0s mi SAuDpernumerary (site 141%) wv Company Sanitized. Does not contain TSCA FBI -_-- TT 124768: DevlopmentalToxicitySudy in Ras Dupont6s1s - INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP TT: 100 N/KG/oRY PoFEmmTUwSo.NWoo..epeerwvsswwrr.. ssmtuaevrewss ewFwrmoemles)) ccuunsssstreereoammionr sass (cont) vertebra s 5.96 Kidney Rpaept(iacireldnaedchaorss)isziefic3at(iionn) == :5: S513i57s5 xsiwnaeny : 55 Kidney 3PRaeptiairldaed-ossisziefic3at(ixot)n (bi) wVR Fapiita - Sizes (bid) w= be12t 2H o6a y Swwiompernumerary (site lb) ov 3 Zo wo se7:s 5s5s0 vertebra Rneotarded ossitication 5 s.60 xsdney a son Swa(Tlrcdeenamiaespieisl)l3a10-)size 2 = w wo ::5 HSsEenA mn : sia xwStoopermumerary (site 13 bil) ov oh - 1i5 $i552n05 KSiadanrey RwPeaotpairldlead-osasiizteto3attio)n (2 bil wVR 3ii2 55Sk86 iney wfSimos)al papilla - size 00 sas21 s 6o.2o1 xiney Swmoall papilla - Size 2 bi) 3i5 5HS1eh07 idney nwPaodpiila - size 2 a) w : se wo _-- Company Sanilized. Does not contain TSCA CBI Ee H-24766; Developmental TonicityStudy inRats DuPont-6515 -- INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP III: 100 MG/KG/DAY MoFEEaTWUSwSoN.NO/O.. P_sEETUSSWWIr..STSTRRUUCCTURREE . s48gd578 (cone)5.22 Kidney 1055 5s5a8z2 Kiney sian 112 7 Sle seas1er 2.09 spleen SVteerrtneebbrara 23 s5a6 a5 s5l3e9s 5 S31 vertenra 57 5a3.45 son vertebra --~ 105 55.7457 vertenra u1n2 5 s5a0s0 shan is iise s5i2z0 Kidney sess193 5.56 H23 eslds 5587 ska PFIINNDDINGG(5S)) SmaQltlispiazpeill3aze-) size 2 nPaapnilla n> - size 3 (1t) wxD0 CLcAuSaSssItFiIcCATTIIOONN w wr MPialsealigned (1) Retarded Ossi fication oxv wo(cen ths) w rAeDy RaeDtarded Ossification wo(cen that) w RReettaarrddeedd OOssssiifiiccaattiioonn (2511) VR wo(cen thio) = aRept(acrendedtOh7s,e1i2f)ication w NRAeDtarded Ossification (v1) WR SaeDall papilla - Size 2 (bi) WR a>o RNAeDtarded Ossiication (2 bil) VR _--m Company Sanitized, Does not contain TSCA CB Ties L1L2244776688:: DDeevveellooppmmeennttaallTTooxxiicciittyy SSuduyiindnRaRytass______ DDuuPboonwt66s5i1s5 -- INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP TIT: 100 WO/KG/ORY oFwEsTUS0.N/o. _rerUS wr. _sTRucTURS enone) cuassteicaTion 60593 (cone) vertebra RetTaexendedtuors)sification w s:5 spF.6td1 00 0 0`5 SS$7a76 sent san R5etarded Ossitication (2 B41) WR Retarded Ossitication (2 51) WR F2y SSi5a0 vertanra iRebtarded ssiication 31 ssli m wwooGeen what) w 3 523 vertenra RetTaerendedenostaiit)ication = esa23 s 65.2035 wnoo 3i: sSlp1eo2d wnnooo ~ :5: sspiiitat wwoo wo 115 p5sit6s wwwoo 23 s$n5 1 sia xJ0ed 113s S$$i52e63 xidney wnoo Small mapilla - size 2 Gi) WR H Bt wo sasT s 5.52 wo = _-- Company Sanitized. Does not contain TSCA CBI aos H:24768 DevelopmentalToxiityStudy in Rats DuPone.6515 -- INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP TI: 100 MO/KG/oAY oFEwTUSv0.WO. Fetus wr. staveroms enon) cunsstrrenTion 6as55295 (cont)Ssin mmeb SSuuppeerrmmuummeerraarryy ((ssihtoert13113ts)t) DovV :5i piSi 5s1 Sem m2Reoptarded Oseitication (bil VR 1:5 SSS7ss2e san wJReewstarded ossification (611) wk nw Sl66 Kidney Suall Fapilla - Size 2 BAD A cuss7es suas 2 ped awdo 5i3 i552z67 xianey nsPaaobpila - size 3 (rt) w= 5: ` 5si11 ae nSeubypermmerary (site 1B) ov fe15 TSol5so an nao0 Sipernumerary (site 1b1) ov - 32 SShi mmee SSuuppeerrnmummeerraarryy ((ssiittee 114477t%)) 45 cea7se 5.29 vertebra Ret(aCrednedeaots)sification w 52 S5.8209 vertebra Rweot(acrednederois0s1i2e)ication = :5. pi 5.t2]7 xx0 5 Be fies _-- Company Sanitized.DoesnotcontaincontainTSCACBI Tar 24768: Developmental xii Sty in Rats Duroncssts _ SHDIVIOUAL PETAL WEIGHTS (grams) AND ALTERATIONS amoup 131: 300 e/xo/oAY FsEarobwoi.. _seros wr. _swocruns enone) consssareation cas:os (conc)La versesna s soe wReot[aErhdred ossitication i30 H i E. x se vertebra Rbeotfazdeed osositicacion Rotaried S3tiHoacion han w can:on 5.67 verveora RetRazYded ossification w i3: Sisoeabe vestenra wRwesotarded ossitication :s Hses --. RweoR(aoxndadtroiesrsification - 5:) iBriey nwos{en tees) Wo - iii HHii Hn uwneoo r -- r ----------`Com-- pany Sanit-- ized. Doss-- not conta-- in TscA col Bre H-24768:Developmental Toxicity Study in Rats DuPont.6515 -- INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP IV: 400 MG/KG/DAY oFEaTUSwo.N/O. FETUS Wr. STRUCTURE FnomG(s) cuasstricaTIoN ea1s 4.56 32 aillmss s5 3s0l6s7 vseartmebra 25 a3.2902 55 s5o0s3 u1n0 aalsme 112 sslleas 11s 5lselss sm n1 ialnse ska waD> RweDtarded ossification (2b51) VR Ret(acrednedth1o1s,s1i2f)ication w awo waD> NwDo xwapn SRAeDtarded Ossification (241) VR eReytarded ossification (1) w seas1as 5.30 32 S52170 sku --~ H 1 vesretnebra s sas Vmesbtebra s 3 SRikpil 57 45.2440 Sskuublclutis s 5535 vertebra 10 sa2 skal Rweotarded ossification (2,361) WR Reeytarded Retarded oOssssiiffiiccaattiioonn (bil) VR RSeutp(aecrrednneudntOehsriias,ri1y2f)i(csahtoirton141c) o=v Sup(ecernnmtehr1a2)ry (site 141) Retarded Ossification (2,361) ww VR HReemtoarrrdheadgeO.ss(ihfeiacda)tion RetardedOssification (2041) VR Ret(acrednedthOis,si1f2)ication (2541) VwR _-- `Company Saniized. Doss not contain TSCA! cal Tia eee H:24768: Developmental Toxicity StiundRayts DuPont6515 ~ INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP IV: 400 MO/KG/DAY EaFWEwTSUwSoNH.OO.. P_ReTerUuSS WwDr.. ST_sRTUeuCcTToURRe.E POPNoDImNGs()S) CLcAuSsSsIrFeIreCaAtTiIoOnN eEsSs2s (cont)5.00 vertebra Retarded oasitication 2n 1 5a.e20 Ya sakbal san RSeutp(aeGrredmneudmteharGzaa)rsyifi(csaitteion14b(ibl)l) wVm Dv Retarded ossification vertebra Ret(at3d2ed2Cias)i ication ww 5 4.97 vertenra 3 444 soa Ret((aCGreednnedtthh11O0os-,s11if31)i,1c3a)tion w w Retarded Osbitication (m1) VR Vertepra RettaerednedthOaa,s1i2f)ication w cies7z6 5.96 subcutis Vertebra HReemtoarrrdheadgeOss(ichiincta)tion x 23 a PisRoT $16 ashban RSeutp(aecrredmneudmteirCaae)rsyifi(csahtoriton13(1260)81) wVa DY Retarded ssiication (bil) VR -~ 5c7 i33l31e72 Sternebra sternebra a is Rwextarded Oasitication (6) = >Retarded ossification (6) = 105 1 3i65 idney iz mwPaobpilla - Size 3 (left) w 1F2l 1 3l3a1s sternebra 3s mRwenptarded ossification (6) w= 1156 3al0e6e stemebra Saetarded ossification (6) w ssa2s132 aa.162 fwyp 3 iss ao Company Sanitized. Does not contain Tera oy -_-- Tras H-20768: Developmental Toxiiy Study in Rats Dupon6s15 --~ INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS Grown 1 00 vo/Ko/onY FoFEEtTSsv0N.WO6.._Freeroswwni. o_msmoacverroomse eennoon(se) ) ccausssreezrooamtzioonr sassi:az cont.)i FET o : bY RSkeiatpaerrdneidmeocsasriyti(ciacteion13 (b2 ibil) woRv 3:5 iiUo san RwWeootarded ossitication (2 bi) va r32d 3b5i % son wRweeotarded Oasitication (2 bil) vm ii iHiEYSon wSReiotpaerrdmeudmeGraasriyti(csairtieon13 3bilb)i) ov asz?s wssa nwoo :3: HIiE H ean nRoeoytarded ossification (bil) wn :;: 8iik san RaWeootarded ossification (bil) vw - 0i5 H5onE5 FS in nwwooo fy 3ii iipir wwwooo sas:3 s 50%8 sn Rwetarded ossification (bil) vm Torsone 5 aso Rweoceaernaeatiossiticarion = -_-- CompanySanlized. Does notcontTasin mat Tie HL24768: Developmental Toxicity StiundRatys Dupont6515 _ INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP 19: 400 MOK/onY IaFEETTUSSw0N.WoO/.. F_EpeTTuSsWwDr.. SW_sOTCauTcTOoRRsE nmeommoss)) ccuusasssttriiocaaTmioon S653 9 (Cone.)G42 vertenra Ret(acrednedthoiaos,i1f1i)cation = s`: a iali 0wwoo 10.5 Jpai Ea 0wwoo 123 ipisne Jwwooo 1 iE wo seos7a0 4.20 vertebra Retoarndederaons)sification w 2 66 sVearntena RReetteaarrnddeeddthOiOsoseo1ii3t)iiccaattiioonn (bi) va w 5 4.29 vertebra . 486 san RReett(aacrroddneeddthaOOrssas1ii3fi)iccaattiioonn (bil) wvA Vertena -~ s 034 vertebra RReett(aacrreddneeddthOaOaonaa1ii2tt)iiccaattiioonn = 5 430 vseretnebra RReett(aacrreddneeddtnOOass)eeiittiiccaattiioonn (bil) wVR . 4.52 vertebra s as2 sw Ret(CaCerendnedtthhOiasote11a32))ication = w Retarded Ossification (bil) VR Vertebra 5 65 vertenra RReetc(aaGrreddneeddtrOO.ssas2si0.ii2cc5aa)ttiioonn w priytti w CompanySanitized.Doesnotcontain TSCAcat ee--r--esend 124765: DevelToocpk SmtuedyinnRatts Duponcgs15 --~ INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GRoup 17: 400 wo/K0/DAY Eorwoswosbs. remus wr. sevens enomos) cussterontion -- to Ler vertebra n 07 Kianey sReeteaalnsdeeFmaapaioisisiaiat)i"csaitzieon2 bil i=m Vertabea 2 8 vertenra RReetteaaerrndaeedathoidmosa-iiitnFi)icceattiioonn w n wes ws(Con tates) = ass:3es iwens wwoo ::3 o$iae5 rane : soe Swwaooil pita sire 2 0 ow wo : TE vertebra . sa wReot(aerednedthioos)siticacion w s HE g----" 0 5.20 wReoTaerednedeaons)sification = Fd Hd wo --- sass:3ss s0i2 AKidney 3 ie SwSmisaplelrmipmaepcilalray -(ssiitzeea2nilb)i) Bwmy ::i iS867 sKiaanney ESReSatalrdeadttoshseificastiizoen (bGi0d)) wm ::5 $ii8o vercenma Rwweoovarded omsitication 1ii0 pT5.tE03 rioney Sweoaenonmaspi]iia - size 2 ro) w wm wo CompanySaniized.DoesnotcontainTSCA CBI --_-- Ta ---- H-24768: Developmental Toxicity StudyinRats DuPont-6515 - INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP IV: 400 MG/KG/DAY oFEaTUSN0.N/o. FETUS Wr. STRUCTURE PING (5) cuasstercaTION Gas3sss (cont)3.54 Kidney Seal papilla - Size 2 18) WR sass7ss 4.69 23 i ilsk2 sem ie sn 5`7 slaleoss san .5 apisess 110 3i7n sm 132 a5627 skull aRe0tarded Ossification (bil) VR RNAeDtarded Ossification (3b) VR XReAtarded Ossification (bil) VR AADD AReDtarded ossification (201) VR AReDtarded Ossification (bil) VR AD sass1eo 5.27 23 slalose i i verter - `5 ainm 57 ii5s2 sKikdanley saz 0n S15s5 mvewrtenra 2 4.75 vertenra Bn 4.87 vertebra wroy aReDt(acrednedth1o1s,s1i2f)ication w 0iy RPaeptialrldaed-Osssiizefic3at(irot)n (bil) wVR Swuopernmumerary (site 14b1) DV Ret{aerednedOhs10s,i11f)ication w Ret(aerednedthOas)sification w RettaerednedthOassification w sess1es as EY Company Sanitized. Doesnot contain TSCA CBI Te H-24768: Developmental ToxicityStudyin Rats DuPont6515 -- INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP Iv: 400 MG/KG/DAY oFaEtTUS0.Wo. _rerus wr. stRucTRe noma) cusstercation cans2es 3 (cont.)16s 38 sveartlebra ` a6 Vesrktaelbra 5: 3.i8n9 7s i 35 san 05 i35E8 RSban a= i 30 sternebra RReettTaaerrenddeeddtnOo)ssssiiffiiccaattiioonn (bil) WR w RReettaarrddeedd Oossssiiffiiccaattiioonn (bil) VR wwTeen thaz) = waReDptarded ossification (bil) VR SRueptearrnduerderOasrsyiti(csaitteion14b(ibli)l|) DVVR wNiosaligned (4) ov seas7:70 4G7E2 KSiadanrey Vertebra 3i da0z7 vertenra - s 4.30 KKiiddnneeyy s 4.80 vertebra ' 5.09 vertepra 355 541.71656 sveirdtneebyra Fon] a35n5 san 5 ae SRRmeeattlaalzrddeerddapOoissssliiltf-aiiccaaSttiziieoonn2 ((bbiill)) WVRR wp(cen th12,12) = Ret(acrednedeh1o2s)sification w uPaapilllapapislilzae- 3si(z1e) 2 (rt) V=R Ret(aCrednedthaots)sification = Ret(acrednedthaats,s12i)cation w wPaopilla - Size 3 (xt) = Ret(acrednedthoaons1i3f)icat ion = wReptarded ossification (pil) VR [4 CampanySanitized, Doesnotcontaln TSCA CBI Tie H24768: Developmental Toxicity SuidnRayis DuPoni6515 ~ INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP TV: 400 MG/KG/DAY oFEsTU3S0.%07. FETUS wr. _sTRuCTRE mms) cusstereation san3s? 2 5i2s2 xidney i55 viiS1a55 sStteermneennrraa : Ve Teirbtebra .:5 05i2se6 111 Vpeeots uun Vieer s0s7:75 w51a1r 3i 5 5i1e0s3 stemnebra sa - :5: S572 er me we P3e5 $S$5535 mmmieis i5 S521 mi u pe cas3es : wV6n vertenra 3 ars wwFaooptila - size 3 (it) = RRSeeittpaaerrrddneeuddmeoorssassriiyffii(ccsaaitttiieoonn145((066))) ==o R0et(acrednedwacaa)sitication = wwwoop w0nDo ao wwjoos RSweuptpaerrdneudmeoraasriyti(csaitteion1b(6)) = OY wSSiihppeerrnnuummeerraarryy ((ssihtoere11b4b)il) DDVV SSSuuupppeeerrrnnnuummmeeerrraaarrryyy (((sssiiittteee 1114a41bx0i))l) FoOSvV wwoo wReot(acrednedaaos)sitication = 10 Commppaannyy SaniSanitized. DonotecontsainTSA cal isos 24768: Developmental ToxicityStudy inRats DuPont6515 - INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP IV: 400 MG/KG/DAY oFEaTUS0,NO. FETUS WI. STRUCTURE. FvDmNG(5) cuasstrrcaTion sees383 (Cont.a7 5s iilss sen 25 3al6s7e spleen 05 iims sen w5o saReltearded Ossification (bi) VxR NaDD Retarded Ossification (ext) VR seos1ss a3 mb 2 835 vertebra i3 d5.e4 mKiipdney 5: s$3l6s vertebra 7e 4$559 Rsikba 5 3027 Rsiubbeurts 0 5.01 vertebra - 112 i4.s81 SRitbernebra Fru 3ie%r SRueptearrnduemderGaarsyifi(csaitteionl4bil) DV se(aclenptahpiiol)la - Size 2 (18) wWR Swubpernumerary (site 1bil) OV Rettaerednedth1o1s)sification w SReutpaerrdmemderGaarsyifi(csaittieon1ar(tb)il) wVR SHuepmeorrmruhmaegrear(ychests) x Retsahrodreed o1sasritfsisciatteio1n416) w Mis(acleingncehd11,(132,)3) wwv SwuDpernumerary (site 1bi1) DV wo seas1ss 5.79 : sel Staewsnepra Vertenra 15 55.7385 SRitbemebra 0Supernumerary (site L4bil) DV RWiestaalridgendedoss(i3f,3i)cation ov Mis(acleingntehidl-(133)) wo=v Supernumerary (site 14bil) DV Company Sanltized. Doss notcontain TSCA Cai TIT 124768: Developmental Toxicity Study in Rats DuPont-6515 -- INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP 1V: 400 MG/KG/DAY oFEwTUSwo.K)O. FETUS WE. STRUCTURE Fn(s) cusstpicaTION se8sss6 (conc. s.a1 ` Sz .7 5s7as 5 5532 1n0 5s55n2 n2 55.54a6 vReirbtebra VKeirdtneeryra vertebra aw RseutpaerrdneudmeOrsasriyfi(csaittieon141) ov mo(cen thiz) w wPaspilla size 3 (rt) we Ret(acrednedtiods)sification ww Rae)tarded Ossificaion wa(con th12) w Supernumerary (site 141) w cas1es 5.17 32 5i.i0s3s 5i s5ii3s% 2` a5l5m0s Rib -- 5e iise 1 ies 1n iieas 113 diasr2 is is xeDy AxaDn SAuDpernunerary (site 14rt) ov axo xaa> onDr ewyo ws sass790 472 wb 2 37 vsertmebra 3 a6 RSeutpaerrdneudnerOasrsyifi(csaittieon1ab(i2l0)11) WoRv wReat(acrednedthOis)si ication w Company Sanitized. Does not contain TSCA CB 2s ZH:2T 4768:DeDevveellooppmmeennstaallTTooxxicclityySSutdudyyiinnRRaattss DuDuPPoonmt6S5i15s -- INDIVIDUAL FETAL WEIGHTS (grams) AND ALTERATIONS GROUP IV: 400 MG/KG/DAY ZoFEnETtTUUSwoN.KOO.. FEFETTUUSS WWIr.. STSTRRUUCCTTUURREE 5485a50 (cont.)3.88 vertebra `5 7 45.719 mKibdney 503 5o sl5a0t5 am 11 45.60s0 mip B1n2 u silo m 49 mm see1s7 ao 2 307 vserotmebra i3 i4.7n6 `5 5.i60mam 57 aslias7 -- 105 slsios 1u sioma skun FFIrNDmDiIGNG(S5)) CLcAuSasSsItFrIiCcAaTTIIOoNy Ret(acrednedthiO1s,s1i2i)cation papilla - size 3 (rt) wwr wSubpernunerary (site 141t) w >Supernumerary (site 1416) ov SwuDpernumerary (site 14xt) ow wwDo. Supernumerary (site bil) ov Rweotarded Ossification RetardedOssification (bil) VR wp(cen thi1) w W>avy (5-205) 0 = 0x0 0na NReDtarded Ossification (bil) VR Company Sanltized. Doss not contain TSCA a1 -_-- Tis H24768 Developmental Tosicky Sudy in Rats Dupom6s15 APPENDIX H - Analytical Report `Company Saniized. Doss not contain TSCA col = ---- H-24768: Developmental Toxicity Sudy in Rats DuPont6515 - A. SAMPLE SUBMITTAL All dosing solution samples were collected on the same day the solutions were prepared for the study. The solution vehicle was deionized water. B. METHODS 1. Analytical Methods a. Dosing Solution Treatment MSaamypl4,es20c0o1ntafoirniunngifHo-r2mi4t7y6/8coantctehnetrcaotnicoenntvrearitfiiocnastioofn0a,n5d, S1-0,hoaunrdr4o0ommgt/emmpLerwaetruerecostlalbeiclitteyd. on `Samples at the same concentrations concentration verification analysis were collected on May 11, 2001 and May 22, 2001 for dEialcuhteddocsoinntgroslamtpole0,.5prmioLr ttootaalnavloylsiusm,ew)atso adinluetxepdecwtietdh cmoentcheanntorlat(i0o.n5ofm2L.)5anodra4.n0ammgo/umnLt o(fa... `Samples submitted for analysis were analyzed the day the solutions were received by the testing group. - b. Chromatographic Conditions Instrument: Colum: Hewlett-Packard Model 6890 GC HP-1,30m x 0.32mm ID, Injector: 0.25 um film thickness Split, 250C Detector: Carrier Gas: FID; 300C Helium (2.6 mLmin) Split vent: 52.9 mmin Injection Volume: 1 microliter Oven Progra: Gradient Initial Temperature: 50C Initial Time 0.0 min, LLeevveell | | Rate: Temperature: ~~ 40Cimin. 300C Run Time: 22.25 minutes Company Sanitized. Doesnotcontain Tra cay ise 1.24768: Developmental Toxicity Study in Rats DuPont6515 c. Calibration and Quantitation A stock solutionofthe test material (a separate sampleof H-24768 used as analytical reference) was made in methanol. Before analysisofthe samples in the study, appropriate aliquotsofthe stock were diluted with the methanol after an equivalent amount ofthe diluted control to match the samples was added. These solutions were used to make calibration standards that bracketed the target concentration of the diluted dosing samples. Peak heights (4 retention times) from GC analysisofthese standards were used to construct calibration curves by least square regression (see Figure 1a - 1d for a representative calibration curves). Measured concentrations for dosing solutions were determined by applying the peak heights from replicate injectionsofthe samples to each calibration curve. The mean result from the concentrations at all retention times (n = 4) isreportedas the concentration for the sample. Test substance uniformity in the vehicle was evaluated by calculating the coefficientof variation (C.V. = standard deviation/mean x 100)of the measured concentrations in duplicate samples for each dosing level. A coefficientofvariationof less than 10% is the standard riterion at Haskell Laboratory for acceptable distributionofthe test substance throughout the solution. The mean resultofthe duplicate samples for each dosing level was used to determine the concentration of the test substance for the respective dosing levels. Stability was evaluated by using the meanofthe duplicate samples for concentration verification as the baseline for comparing the corresponding room temperature results. C. ANALYTICAL RESULTS 1. Chromatography H-24768 eluted from the GC column as resolved peaks over retention time range of approximately $ to 20 minutes. For the purposeof quantitation, the retention times of approximately 7.9, 8.2, 8.5, and 9.0 minutes were determined to be representative of the test substance in the dosing matrix. Representative GC chromatograms are shown in Figures 2(a - c). Test substance was not detected in the 0 mg/mL control. Company Sanitized. Does not contain TSCA CBI Te -- B2H-427467688:: DDeevveellooppmmeennttaall TTooxxiiccittyySSutuddyyiinnRRaattss ~~ 2. Concentration Verification and Stability Samples DDuubpoonwt6s51i5s AVenrailfyitciactailonreasnudltsstafbriolimtydoasriensghsoowlnutiinonTsapbrleepIaraenddMSauymm4a, r2y00T1a,balned1.analyzed for concentration The following table summarizes analyses for this preparation. the results for uniformity/concentration verification and stability. PrepDaartaetion NmopmimnLal Meansg/umrled %NAvoemriangael 4May2000 50 ama66 938 410000 839702,388820 885 943 a SDtuapbliilciatytesasmapmlpelseshealndalfyzoerd.hours at room temperature. CV Stability" %_% Nominal 1 91.6 i 89.5 20 mTihxeerdes(uCltVs'fsor=s1a,m1plaensdp2r)e,paatrtehdeotnarMgeatyed4,le2v0e0ls1,(tsahrgoewt =that1t1he.5t%eostfsunbosmtiannacle)waansdasdteaqblueately (no2t1d0e.t5ec%toefdnoinmithneal0)mign/tmhLe vseahmipcllee.when held 5 hours at room temperature. Test substance was - The following tabl i toxicity pilot stud Tshteasbielirteysuslatmspilnedsicfarteomthaatprtheevitoeusst sduebvsetlaonpcmeenintatlhe vseuhpipcolretwtahesssttaabbillietWyiofftenhehetledst4s-udbasytsarnecfeguenrdaetredthfeoclolnodwietdiobnysoSfhtohuirsssattudryo.om temperature and Preparation Due Nominal mgml Measured mgml Average %Nominal CV % Stabiliey' _ Stability" %Nominal % Nominal Marl 50 100 472,454 926 936875 95 3 5 l012 1074 970 972 40000 4602263879 989 91 2 2 1052 203 1033 ws ab SDaubpilliictaytesasmapmlpelseshealmdlyfzoedr4.days refrigerated. Sablity samples held fo4r days refrigerated, then hours at room temperature. e -_ T Company Sanitized, DoesTnotTcoTntain TSCA Ci is H-24768: Developmental Tosicity Study in Rats Dupont6515 3. Concentration Verification Samples Analytical results for concentration from dosing solutions verification are shown prepared in Table May 11,2001 and May IT and Summary Table 1 22, 2001 and analyzed `The following preparations. table summarizes the results for concentration verification analyses for the Preparation Date 11-May-2001 Nominal mg/mL 5.0 100 40.0 Measured" mg/mL. 5.06, 5.03 9.62,10.07 420,406 Average CV % Nominal __% 101.0 04 98.5 3 1033 2 22-May-2001 5.0 100 473,501 97.4 9.22,9.65 94.4 4 1 40.0 373,365" 92.3 2 & MDueplnicastaelsaomfptlheesorpgeirnlaevlealnwaelryesiasnaldyedd.upliCcYa.tercelaellieesdoof tvheerirtyiunniafosramimtpyleofrmepiosrtee,d. ~ t`Thhaenr1e0s)ulatsndfoart tthheesetasragemtpeldesleivnedlisc(attaergtehtat=t+he8t.es7t%soufbsntoamnicnealw)asfoardaelqlusaatmepllyems.ixTeedst(CsVu'bsstlaenssc.e was not detected in the 0 mg/mL sample. 4. Conclusions mReisxueldtsprforpoemrltyh,eaatntahleystiasrogfettehdelsevaemlpslaensddustraibnlgeutnhedesrtutdhyeicnodnidciatteiotnhsaotftthehetessttusduyb.stTaenscte was substance was not found in the 0 mg/mL samples. --_-- ie CormpaynyeSalnfitiizeedd.DDoosessnnooltccoonnttaaiinnTTSSCCAACCBBI BL24768: Developmental Toxicity Study in Rats ANALYTICAL SUMMARY TABLE | DuPont6515 SUMMARY OF DOSING SOLUTION ANALYSES Sample Type May-2001 Concentration Verification Average Measured Cone. SAtvaenrdaagredPDeervcieanttiNonobminal Coefficient ofVariation Subily Nominal: Dosing Concentrations and tailofH-24768(mg/mL) so0 100 00 (04m4n7 0$090) 372 30 a326) 85050) 382 535) 469 038) 885 83) 3 043) 01 01 07 1% 1% 2% asi sos 368 01.6 ) 20) `C1o1n-cMeanyt-r2a0ti0o1nVerification 50s 985 a3 oo) 083) 033) 22-May-2001 457 544 369 ) oa) 23) - Nominal: 5.00 1000 000 7000 `ConcentrationVerification G xn 6 936 wisy 06032) ase on 875 EH 389 on 617 68) Average Measured Conc> 6 505 396 624 SAtvaenrdaagredPDeervcieanttiNonobminal 09 os o89) a 201 04 "09 11 Coefficientof Variation Ed % 2% 2% Subiliy sose a 0 9.708 s21y8 a54328 ws.3a7h 97)h a41n.3y0 6699.67)0 ba C SMNaeumampnbl,eerSssDhi.enapd0adtrrCoVo.emftotermrdpeuehprhlseisrsesspefseacmt3sopihlvoeeusrprc.eerlocefne0invnteyvaalume.forofmmiixtturye. 4 MDuepmlcrteeslstaomrpallelsmsuibmeitsed. Msnrecutrepr 1 SSamaplemsfhpoedmlprreeevfiroisugsersaatdyorfodr oraakndyRseqasumepst Sample Ned rier f4odarys wed by ostr oo npr -- ee ------ TieLomp-- eaneyseanietized-- .DDoronSoOtscSoOn-- tRsaEinTTEsEcNAECBB. 1.24768: Developmental Toxicity Study in Rts Dupontesis - Analytical Table I. Concentration Verification and Stability of.24768 in Dasing Solutions TT Sample TyPprepeuienbue _ NominalmgmlAaaMeessed Few Nominal "hay 2001 ConcentratiCoonnVterroilfication") 00 ND() - s01 an 944 502 Mean: 44965601 53)2 crs 11000012 883900 585900 Mean: 8c.8r55n01 x) 04000.21 13722 995.50 Mean: 3c7r7o50n7 00 Hour RSotoabmilTietmypersture 50 ass s16 --~ Hour Room Temperature 100 595 5 SHour Room Temperature 00 168 (8) Duplicate samplpees vel were smlyac. ian,0. and CV. caleutedtovery 920 ) aDefnoortemsiynorofdietescteed. -- `Company SaniDtoeisnzotecondta.in TSCA CBI TTT Te, -- 24768: Developmental Tricity StudyinRats Dupont6S1S Assytical Table L (continued) Concentration Verification and Stability of 24768 in Dosing ~ TSoTlutions Proponbae Sumple Type Fomine!gel BOE Mezsured Nhomeimel TMar-2001 `ConcentratCioonnVterroilfication(A) 00 NDB) - 501 an s02 pe 944 903 Mean: 4c63v2s01 020 11000012 119356 s91556 Mean: 0c5v.2s0%4 oes) 000012 3a829 1901035 Mean: 3c5.v6s09 059) _ 7001 62 002 611 02 581 Mean: 62.4501 5. cvs 4-DayStRaebifliigtyersed 50 506 1012 5HourRoom Temperature(C) 50 537 1074 4-DayRefrigerated 100 $ Hour Room Temperanure() 100 970 on 970 92 4-Day Refigeated 00 a1 1052 5 Hour Room Temperature() "00 "3 1033 Day Refigrsted 700 5 Hour Room Temperature() kl 5, 2) 1203 95 (4) TDuapliicnatuedseamdplfeosreroemnW,orkMReeaqnu,esStD. () Denotes no dere. imafteodmof miixtuyre. () Samples hed f8odary refers,then Shesstrom mperre _-- Tier CompanySanitizeedd.DDooeessnnoottccoonnttaaiinn sTccanmsan H:24768: Developmental Toxicity Study in Rats Dupont6s15 - Analytica Table I. Concentration VerificationofH-24768 in Dosing Solutions TT Pepmebue Sample Type _ NominalmgmlnonMeeasred Neomiwnal T1-May2001 ConcentratCioonntVreorlification(A) 00 NDB) jo 501 506 502 503 101.2 1006 Mean: cSoosxm002 aor) 11000012 1056027 1906027 Mean: c585n203 085) 000012 0260 01015s0 Mean: 4c13r0a99 033) 22May-2001 -- `ConcentratiCoonnVterroilfication(A) 00 NDB) -- 5041 an 502 sou 946 1002 Mean: c4a87s202 019 1004 ox 522 1002 Mean: g9.a6s5 es cvs 496.95. "001 373 933 40000224 338437 9565388 2002me8an(: 336654 991130 _ (A) Duplicatesamples per evel wer analyzed. Mean: Mean, 5.0. c3c6w9r2n06 [2X] 3nd C.V. callie 0 very anforofmmiitrye ((8)) (DM2e2ev.o2re)e.nsottTpdheiotescrtmeeed.anfoetshlo oaigsinsaleadna3lyhsiesocfSoanmpcleer2n(2o)rnSdamuplep3 sandsvluatgs fwihh Soermgpilneal1sorpsehe epored concen of he 40 mL sample -_ Tia Company Sanitized. Does not contain TRA At ALH2-244776688: DoDevveellooppmmeenntaallTTooxricctiyySStuuddyyiin nRaRtsas_____ Representative AnaFliygtuicrael1Calibration Curve Eq2u0a.ti0o3n49fo9r4th+e 6f.it6t3e3d6li+neXs i ReSquared = 0.9976 DubPuopnomts6s51i5s Concentration, mg/mL Figure 1a: rCeaplliibcraatteiponeackurvheei(gRhTt.me=as7u.r9emmiennuttses()sqsuhaorweis)ngolrinceaalribfritat(iionne)sotloutions of H-24768 diluted over a concentration range of 1.56 to 6.49 mg/m. ao] EYquoatinonifor hewfoirnesdelninex oo] Resausrea = 0.9972 i0 Concentration, mg/mL Figure 1b: Craelpilbircaatteiopnecaukrvheeig(Rh.tT.me=as8u.r2emmiennuttses()sqsuhaorwesi)ngfolicnaelaribfriattliionnes)otloutions Of H-24768 diluted over a concentration range of 1.56 0 6.49 mg/m. CompanySanitized.Dossnot cantain TSCA CBI TT-- H:24768: DecveloopmmenotalTTooxriccityySSutuddyyiinRRaatss RepresentaFtiivgeurAena1ly(tciocnatlinCuaeldi)bration Curve 144 Equ5a0t1io3n20fo4r7the+ f2i.tt0e4d19line+: X 10] Resausred = 0.9967 i Fl i DuDubPoomnet6s5i1s5 Concentration, mg/mL Figure Lc; Craelpilbircaattieopnecaukrvheei(gRhtT.me=as8.u5 remmiennuttses()sqsuhaorweis)ngfolrinceaalribfrtat(ilonnc)sotloutions of H-24768 diluted over s concentration range of 1.56 o 6.49 mg/m. 254 Equ5at-i0o.n1f70o4r7t4he+ f3i.tt9e0d72lin+e X 2 R-Square=d 0.9977 I z 23 Concentration, mg/mL Figure 1d: Craelpilbircaattieopnecaukrhveei(gRh.tTm.e=asu.r9e-9m.e0nmtisn(ustqeusa)ressh)ofwoirncgalliibnraartifoint (linc) to solutions of H-24768 dilutedover a concentration range of 1.56 t0 6.49 mg/m. Company Sanitized.DossnotcontainTSCACBI - ae 124768 Developmental TosS i diny Rats Dupors1s [ || p ew!af ---- | - Figure 2 Representative Gas C hromatographyChromatograms | | | wf [a | wf | || [= J | Ler ] [Figwuyore e2a: oRerprHe-s2e4n7t6at8iavreeGaCpepcrhoerxoimmeaatteolgyra79m,o5f0.2,m8g5/,maLnd(c9o.n0tmrioln)ustaemsple. Retention times -- used | wf ] IJ I I 53,E || [I i | | E JTp e e e -- Figure 2b: nrReoepmprirenessaeelnnttcaaotnticvieevnestoGrlauCttiicoohnnroiosmf4a2t4..o000gmrmaggm//mmoLLf..40T.0hemgm/eamsLurHe-d24c7on6c8endtorsaitnigonsoolfuttihoen diluted to a [[== | [a---------------- ow [J . || I" %5. 2 | [I - I Figure 2: Represey ntatGivCe chrome atogram of 3.25e mg/mL H.24768 ee] analytical reference solution TT CompanySanitized." Do nots conts ainTSCACAI c--------------------------