Document gDN0k2JO2VKKrRKEadVL6MBVa

M326 -- 3262 " 125231:OneGeneration Reproduction Stody in ats #R2a6 _ 3263 Duron: 9763 `TRADE SECRET Study Title 'H-25231: One-Generation Reproduction Study in Rats Volume 1 of3 `Laboratory Project ID: DuPont-9763 AUTHOR: Eve Mylchreest, Ph.D. ~ STUDY COMPLETEDON: January31,2003 PERFORMING LABORATORY: E.L du Pont de Nemours and Company `Haskell Laboratory for Health and Environmental Sciences Elkton Road, P.O. Box 50 Newark, Delaware 19714-0050 `WORKREQUESTNUMBER: ---) Service Cop|Nowe [EN --~ wre `CompanyBanhized, Does fot cortalhTSCATET 25231:OneGeneration Reproduction Sty in Rts DuPont.9763 -- GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT TLahbiosrsattuodryywParsacctiocneduSctatneddarindsc,omwphliicahnacreewciotnhsiUs.tSe.ntEwPiAthTtSheCOAE(C40DCPFrRinpcairpltes79o2f)GGoooodd LiatbeomrdaotcoruymePnratcetdicbeel(aosw.reTvihseeditinem19li9s7t)edpduobleissnhoetdiimnpEaNctV/thMeCv/aCliHdEiMty(o9f8t)h1e7s,tuedyx.cept for the `RTehgeibounlakl tAensatlsytuibcsatlanSceervcihcaerasc(tRerAiSz)a,tiaonnoannd-GsLtaPbillaibtoyraantaolryy.sesThweesree apnearlfyosremsewdearteDiunPcoonmtpliance wLiatbhorraetgourlyatPorrayctgiuciedeSltiannedsa.rdNso;nheowoefvtehre,atfhoereanmaelnytsieosnewderaenacloynsdeuscwteerdeinpecrofmoprlmieadncuendweirthGood 1S09002 regulations. Allofthe analyses are considered valid and sufficient for the purposes of this study. Appli/Scpoansnort: E`LWildmuinPgotnont,dDeeNleamwoaurres1a9n8d98Company USA. ~~ StudyDieter: ne. PhD. Date Sie; Toxicologist Applican/t Sponsor: "DuPont Representative sr D-- ae -- SS a Company Sanilized. Does not contain TSCA Cal 1125231: OneGeneration Reproduction Study in Rs --_ `QUALITY ASSURANCE STATEMENT DuPont 5763 `Haskell Sample Number(s): 25231 Dates of Inspections: Protocol: February 25, 2002 Conduct: March 25, 2002; May 2, 2002; June 7,24, 2002; July 9,25, 2002; August 2,569, 2002 `Records, Reports: August 23,25, 2002; September 30, 2002; October 1-4, 2002; December 10-13, 26,27,30,31, 2002; January 2,3, 2003 = Datesates FindFiinngsdings ReRepporteod rted t0: `Study Director: January 7, 2003 Management: January 31, 2003 Reported by: "7 9 QuMaaltithyeAws.sFuarree, B37 31-a3ie4-2003 -- 3 Ccompany Sanilized. Doos rot contain TSCA cat 25251 OneGrainReprcionSty nats Pa CERTIFICATION Dups7es We, the undersigned, declare that this report provides an accurate evaluation of data obtained from this study. SoocrvmGtee 3 a fa-- Pate PrfeeeeaeeaAzCtEd ric BeCav abl 29-u7f1-2003 Aosic alos = Evaluationsby: CE Fm Rvs 3[- EJyan-2203 Pin aFuiogs Ansoa ricSPer ielnsT ssGa r f t= 31 T2_n2003 soTmeonSsavana Appi: . ferr s.rsrton eaFD 21-T--h-2003 ued by Study Director: Tlosn 31-Ja=n1023 -- este eens `Company Sanilized. Does rst cartain TSCA CBI H25231: OneGenerationReproduction Study inRats DuPont9763 ~ `TABLE OF CONTENTS Page GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT... 2 QUALITY ASSURANCE STATEMENT ec. 3 CERTIFICATION corrosion LISTOF TABLES c.crrnrmcnmmmmensssssmmmmsssssmssmmssmsndd LIST OFAPPENDICES co sss STUDYINFORMATION ccna| STUDY PERSONNEL vcore 2 INTRODUCTION... 16 OBJECTIVE crreremmsnsmsssmmmmsmmssssssmmmsmssossone MAATToS SEUABSNRIADNMGIEEwTArHsOeLDrScSormn.r.mcr.mcscroernrrricnnrrnmrsmmssnssmmsssssssssssssnsssnsnsssnssrnoerl 1 dT ~ B. C. TAeRStASLPECHIUESSDANrGrLYrmrmr rnrmmrmrmsrmo nenmimrmsnmsr mssssssnsss sn dT] d D. B. QSUMUY DAOIaGdAPINEcEriSwtrPNEeOrE.e.r.msrmmmrmmnsssmsmsrsmmmmmmssmmosnd18 F. G. AAnalsyticsal Mi(e0tGhgroodu-nspsTaemnstdSSeutbUsdtnYancte AdmSitni.s.t.ration, Preparation, 9 and Sampling.........19 HL 1." BFoooddy CWoensiugmph--ttiPosyn RanAdSFcoeodcoErfcfcincriaer--nrcePmyeRmoAneSnr.mm.as.mmsmsss sins 23 23 J. Detailed Clinical Observationsand MOTalPiy ty RAS... 2 7 1, BESOUA onanism --------__ N. . LFiACGUUGRHGOINRPIOINOoCrEeAgUrIeEeSm.r.mrmrnrgrrrmrersnmrssssssssssmsrasmsmsmsmsemsssmmsmssnssoonn 2d3 : A FR ----J R. ABGIONC PAUNOIORY.cerenrr errs Fe sssron 21 |} T. Statistical ARGIYSES overs nsmmm----------L RECORDS AND SAMPLE STORAGE ccc:33 RESULTSAND DISCUSSION crc 34 ~ ANAS LYTICAL cisC e impos 5 Company Sanitized.Does notcontainTSCACBI 1525231; One.Generation ReprodSutcudtyiiRoatns DuPont9763 --~ B. Dosing Solution ATAIYSES...c.c rns33 C. Analytical CONCIUSIONS vv wmmmm---- REPRODUCTIVETOXICITY EVALUATIONS wcrc 31 IN-LIFETOXICOLOGY corr A. PyRats -Mean BodyWeights and Body sosnsssssssmsmssnmmsns 31 WeightGains ....uesnssnnmnnnin3s1 B. C. PPyyRRaattss--CFloiondicCaolnOsubmpStiConravnadnaFd0tM0dOiETofflinCtiseycY.....u.rersssssnnsssnnsnnnisninss 31 38 D. E. ESstProEusPCAyIcEleIEPTarSamcetrerns and Precoital Interval in Py Females 39 vere39 G. Fy OFFSPIING DAA... cermcrmmrmsrrtrersnrS sssssS sssssnsmsnnn 80 HL.FF,yRRatas--tFMeosaond BCoondsyumWpetiigohntasnadndFoBooddyEFWfIeCiiencgGyah.nts......nunvvmssnnsrnnoonnss 81 $l J. K. FFyyRRatsa--CDlteivneislcoaplmOenbtasl LeANrGIvaATanKdStM.OiM.oA.LnY.s.v..v.v.e.s.susnnnmsrmnsnannsnsnnninnds$l1 L. ReprIn-oLifdeToxuicoclogtyCOiNCIUvSIOeNS vcr $1 CLIN"AI. CHAELTPIAOTIHOOwLEerOYGYeErVeArLoeUeAmTeIreOmNrSe.rm.e.mesmmmmsnssmsssristmmmmmmsmsmmnn B. C. CPlitil calACda HUEEMiS INSeUFYTIc Ia OKo GE.r crcn orre rsirnss sismmsssnsssnns4433 --~ D. Clinical PathoI0gy CONCIUSIONS rvs bd ANAATeOMMIOCAILRPIATrHOrLrOGrY rc smer neni enmms smmi ssis snmsmn4tS BF . OIggANE WEGhtDat ecco N mremrrmsrssssssssssmss--ms--ms--mm--nm--sn--nn--8--3 FO -- Eg CONCLUSIONS ores VOLUME 2.354 VOLUME 3mm 456 --~ e eee e G Companye Sanitized. Doesnot contain TSCA CBI 25231: One-Generaion Reproduction Study n Rats DuPon:9763 --_ LIST OF TABLES Page TABLE | SUMMARY OF DOSING SOLUTION ANALYSES... dmmininih `TABLE 2MEANBODYWEIGHTSOF Py MALERATS ccs 54 TABLE 3 MEAN BODY WEIGHT GAINS OF Py MALE RATS ....co0vv smn TAB4MLEAEN BODY WEIGHOTFPS,FEMALE RATS DURING PREMATING ccc 58 TAB5MLEAEN BODY WEIGHT GAINS OFP, FEMALE RATS DURING PREMATING...cocvc 59 TABLE 6 MEAN BODY WEIGHTSOFP, FEMALE RATS DURING GESTATION... 60 TABL7E MEAN BODY WEIGHT GAINS OF P; FEMALE RATS DURING GESTATION. ..c.ccccvrevs 61 TA8MBEAL NBOEDY WEIGHOTFPS,FEMALE RATS DURING LACTATION cen 62 TABLE9MEAN BODY WEIGHT GAINSOFP, FEMALE RATS DURING LACTATION ccd TABLE 10 MEAN DAILYFOODCONSUMPTIONOF Py MALE RATS DURING PREMATING.......c 64 TABLE 11MEAN DAILYFOODEFFICIENOFCPY,MALERATS DURINGPREMATING. J TABLE 12 MEAN DAILY FOOD CONSUMPTION OF P, FEMALE RATS DURING PREMATING........66 TABLE 13 MEANFOODEFFICIENCYOF P,FEMALERATS DURINGPREMATING. A TABLE 14MEANDAILY FOOD CONSUMPTION OF Py FEMALE RATS DURING GESTATION.....c00.68 ~ TABLE 15 MEANFOODEFFICIENCYOFP,FEMALERATS DURINGGESTATION ccs TABLE 16 SUMMARY OF CLINICAL OBSERVATIONS IN PyMALERATS c 0 TAB'LAEND1C7OSHAUBMIMTAATRIYONO.F.C.LIeNvIeCrALOBSERVATIONaS nIN Pm; FEaMA--LER--ATS DURING PREMATeInNmmGmndll TABLE 18 SUMMARYOFCLINICAL OBSERVATIONS IN P, FEMALE RATS DURING GESTATION .....72 TABLE 19 SUMMARY OFCLINICAL OBSERVATIONS IN P, FEMALE RATS DURING LACTATION......73 TABLE20SUMMARYOFSPERM PARAMETERSIN PyMALERATS ccs Th TABLE 21 MEAN ESTROUSCYCLEPARAMETERS ANDPRECOITALINTERVALIN P; FEMALE RATS 75 TABLE22SUMOFMREPARODR UCTY IVE INDICES: P; GENERATION... wml TABLE 23 MEAN PUP NUMBERS AND SURVIVAL: Fy GENERATION... TT FABLE24MEANPUPWEIGHTS: Fy GENERATION... smd . {ABLE 25 SUMMARY OF PUP CLINICAL OBSERVATIONS: Fy GENERATION... T9 {ABLE 26MEANBODY WEIGHTS OF Fy MALE RATS cvs 80 {ABLE27 MEAN BODYWEIGHTS GAINS OF Fy MALERATS... st SABLE 28 MEAN BODY WEIGHTS OF Fy FEMALE RATS... min FABLE 29 MEAN BODY WEIGHTS GAINS OF Fy FEMALE RATS cnn 83 {ABLE 30MEANDAILYFOODCONSUMPTION OFFy MALERATS ccc $4 FABLE 31 MEANDAILYFOODEFFICIENCY OFFy MALERATS oc 8s ~ {ABLE 32 MEAN DAILYFOODCONSUMPTION OFFi FEMALERATS. R--. ------------------------------ 7 Company Sanitized. Does net contain TSCA CBI F25231; OneGenerationReproduction Sadly inRats DuPont9763 "TABLE TABLE 33 34 MEANFOOD EFFICIENCY SUMMARY OF CLINICAL OF Fy FEMALE OBSERVATIONSIN Fy RATS... MALE ensnasens RATS... -- 88 TABLE 35 SUMMARYOFCLINICAL OBSERVATIONS INF;FEMALERATS... 9 TABLE 36 SUMMARYOFDEVELOLPANDMMAERKNSITN iARALTS... 0 TABLE 37 SUMMARYOFHEMATOLOGY VALUESFOR Py MALE RATS cc 91 TABLE 36 SUMMARYOFHEMATOLOGY VALUESFOR P FEMALERATScc 93 TABLE 39SUMMARYOF SERUMANDPLASMACHEMISTRY VALUESFOR Py MALERATS..........95 TABLE40SUMMARYOF SERUMAND PLASMACHEMISTRYVALUESFOR P; FEMALE RATS........96 TABLE 41 SUMMARYOFURINALYSIS VALUESFOR P; MALE RATS... 91 TABLE 42 MEANFINAL BODYAND ORGANWEIGHTSFROMMALERATS - Py ADULTS... 98 TABLE 43MEANFINAL BODYAND ORGANWEIGHTSFROMFEMALERATS -Py ADULTS ..........101 `TABLE44 MEANFINAL BODYAND ORGANWEIGHTSFROMMALERATS -F; ADULTS... 104 `TABLE 45MEAN FINAL BODYAND ORGAN WEIGHTS FROM FEMALE RATS Fy ADULTS... 107 `TABLE46INCIDEONFGCREOSSS OBSERVATIONISNMALERATS - By ADULTS cv 110 TABLE 47INCIDENCES OF GROSS OBSERVAITNIFEOMNALSERATS -Py ADULTS... 111 TABLE 48INCIDENCES OF GROSS OBSERVATIONSINMALERATS - Fy ADULTS ccc 12 `T4A9INBCIDLENCEES OF GROSS OBSERVINAFETMAILEROATNS-SFy ADULTS... 13 --_ TABI LE 5N 0INCRMIADTESNA-CPESyLAADNUDE LTLSESIvONvGRADES OFMICROSCOPIC OBSERVATIONS 18 TABILNEF51 IENCIRDMEANTCSA ESPAyL NADDULELESTISONr GRADES OFMe ICROSCOPICs OBSERVATIONS --) `TAIBLNEM5A2LIENRCIADTESNCFEySAANDDULLETSSIONrGReADvESeOFMrICeROSCOPIC OBSERVATIONS 2 TABILNEF53IE NCIDRMEANTCSA ESFAyL NADDULE ELSTISONrrGRADES OFMICROSCOPIC OBSERVATIONS 28 TABILNEF5E4MIANLCEIDREANTCSES- FAyNWDELAENSLIIONNGGSRADrESOrF rMICROSCOPIC OBSERVATIONS 26 TABLE 55 INCIDEONFGCREOSSS OBSERVATIONS IN MALE RATS -Fy WEANLINGS ccc 114 `TABLE 56 INCIDENCES OF GROSS OBSERVATIONSINFEMALE RATS - Fy WEANLINGS. cv 115 TABLE $7INCIDENCESOFGROSS OBSERVATIONSINGENERATIONFy MALEPUPS... 16 `TABLE 58 INCIDENCESOFGROSS OBSERVINAGETNEIRAOTINONS,FEMALE PUPS... 117 ~~ Company SaniDtoisnzotecodnta.ininTTSSCC:ACBI 25231: OGneeneration Reproducion Study in Rats Duponts763 - LIST OFAPPENDICES Page APPAEANANLYTDICAILDAXTA cv sm---- 28 APPENDIX BINDIVIDUAL BODYWEIGHTSOF Py MALE RATS... 136 APPENDIX CINDIVIDUAL BODY WEIGHT GAINS OF P; MALE RATS... smd APPENDIX D INDIVIDUAL BODY WEIGHTS OF P, FEMALE RATS DURINGPREMATING. 168 APPEE INNDDIVIIDUXAL BODY WEIGHT GAINS OF P, FEMALE RATS DURING PREMATING.......174 APP`EDNUDRIIXNGFIGNEDSITVAITDIUOANLr BODY WEIGHTS AND Bn ODY WEIGHT GAINS OFs P, FEMALE RATS. 188 APPDEUNRDIINXGGLIANCDTIAVTIIDOUNA.L.B.ODY WEIGHTS--AN--D B--OD--Y WEIGHT GAINr SOF Py F-- EMALERATS 190 APPENDIX HINDIVIDUAL FOOD CONSUMPTIONOF By MALE RATS... APPENDIX IINDIVIDUALFOOD CONSUMPTOIFOPN;FEMALERATS DURING PREMATING.......207 APPENDIX JINDIVIDUALFOOD CONSUMPTION OF P; FEMALERATS DURINGGESTATION........217 APPKIE NDIVNIDUD ALCLIINIXCAL OBSERVAANDTMOIRTOALNITSYDATAIN Py MALERATS. 223 APIPNEPND,IFXELMAINLDEIRVIADTUSADLUCRLIINNGICPARLEOMBASTEIRNVGAATNIODNCSOHAANBDIMTOARTTIAOLNI.T.Y.DATA sagt -- APIPNEPND,IFXEMMAILNEDIRVAITDSUADLUCRLIINNGIGCEASLTAOTBIOSNE.R..VATIONS AND MORTALITY DATA snl APPIENNPD,IFXENMAINLDEIRVAITDSUADLUCRLIINNGICLAALCTOABSTEIROVNATIONS AND MORTALITY DATA - 245 APPENDIX OINDIVIDUALANIMALSPERMMOTILITYDATAIN Py MALERATS ccs 255 APPENDIXPINDIVIDUAL ANIMALSPERM MORPHOLOGY DATAIN Py MALERATS ccc 258 APPENDIX QINDIVIDUALANIMAL SPERMANDSPERMATID COUNTSIN P, MALE RATS... 262 AP`PCOERHINNDADIVBIIIDIUNAXPLTFAEANMIATMLAIELREAOTSNS..TC.Y..C.R.LEPOARAU METESRSn DURING PRn EMATING AND266 APPCENODIHXSIANDBIVIIIDNUTPA,LAFAENTMIAMILAELOESNTROURATSS. CYCLESeTAmGES DURINGPRE--MA--TIN--G AND mn APPENDIX TINDIVIDUALMATING DATA ANDGESTATIONLENGTH: P, GENERATION...........278 APPPEyNGDEIXNEURIANTDIIOVNI.DU.A.L IMPLANTATION SITEpDATe A AN-- D IMPLANTATION EFFICIENCY:n2 APPENDIX VINDIVPIUPDSURUVIAVALL: Fy GENERATION... wn APP WINDEIVIN DUALD PUPI WEIGX HTS: F, GENERATION. anmimpmdBlS APPENDIX XINDIVIDUAL LITTERCLINICAL OBSERVATIONS: Fy GENERATION... 328 APPYEINDNIVIDDUAILBOXDY WEIGHOTFFSyMALEANDFEMALE RATS. 3 --~ APPENDIX ZINDIVIDUAL BODYWEIGHTGAINSOF Fy MALEANDFEMALE RATS... 43 9 Company Saniized. Does not contain TSCA CBI H25231:OneGeneration ReproductionStudy inRats DuPont9763 --_ APPENDIXAAINDIVIDUALFOODCONSUMPTION OF Fy MALEANDFEMALE RATS... 353 APPMEONRDITXALBIBITNYDDIAVTIADUIANLFyCMLIANLIECAALNDOBFSEEMRAVLATEIROANTSS.,..D..E.V..E.LOPMENTAs L LAr NDMAs RKS,-- AND -- APPENDIX CC INDIVIDUALANIMALCLINICAL PATHOLOGY DATA - Py ADULTS cece 379 APPENDIX DD INDIVIDUALANIMALFINAL BODY AND ORGAN WEIGHTS - Py ADULTS........... 406 APPENDIXEEINDIVIDUAL ANIMAL FINAL BODYAND ORGANWEIGHTS- F; ADULTS .... a1 APPENDIX FFINDIVIDUALANIMAL PATHOLOGY DATA - By ADULTS ccs ovo AST APPENDIX GG INDIVIDUAL ANIMAL PATHOLOGY DATA- Fy ADULTS... ns 620 APPENDIX HH INDIVIDUAL ANIMAL PATHOLOGY DATA - Fy WEANLINGS ccs 164 APPENDIX IT INDIVIDUAL ANIMAL GROSS OBSERVATIONS IN F, WEANLINGS AND PUFS.d.........769 --~ --_ -- ee -- e -- eS----si----_------ Company Sanitized. Does not contain TSCA CBI 2551 OeGeninReproSoty nat Durem sres STUDY INFORMATION SubsianceTesco: [----R Suonmsco -- has-- zl ----------| Submit Noho Nips a Haskell Number: 25231 Composition; | KaoImpuiies: Physical Characteristics: Tan liquid Sabi: TChontdeisttosnubosfttahnecesayppseanroedid0ebnecsteaboifaundierthevas observed. Ssonso. EWi1n.idnugPion,odeDeNlneamwoaturres19a8n9d8Company USA. `Study Initiated/Completed: March 15, 2002 (see report cover page) eee -- eee eee Company Banhtized. Does tain TSCA Cay H25231: One-Generation Reproduction Study in Rats DuPont9763 --_ STUDY PERSONNEL Study Director: Eve Mylchreest, Ph.D. Management: Scott E. Loveless, Ph.D. Robert M. Parker, Ph.D. Supervisor: Deborah L. Tyler Primary Technician: Kellie Mcllhatton Analytical Chemist: Janet C. Maslanka, B.S. Management: S. Mark Kennedy, Ph.D. Clinical Pathologist: Nancy E. Everds, Ph.D. Anatomic Pathologist: John F. Hansen, D.V.M., Ph.D. Peer Review Anatomic Pathologist: G. Tracy Makovec, D.V.M. Management: Steven R. Frame, D.V.M., Ph.D. Toxicology Report Preparation: Mary K. LaRoe Maryanne M. Wilford, B.A. `Wanda F. Dinbokowitz. Management: Nancy S. Selzer, M.S. --_ Laboratory Veterinarians: Thomas W. Mayer, D.V.M., ACLAM. William Singleton, D.V.M., ACLAM. w ~~ ..s_ss' Ses ssoos `Company Sanitizod. Doss ret costain TSCA CBI 25751 oeCron Rpts nat fe ~ 1, negencrmion goroducion sad vas conducted with 12523EES) SUMMARY involving the production of one set of litters. The test material was. isterd once gaily by gavage to groups of male and female C:CD@(SD)IGS BR rats (d2a0ygsroofudpo)s,itnhge, PtyhegPe,negreanteiroant,iaotndroastesswoefre0,b7r5e,d5w0i0t,hionrt3h5ei0r0rmegs/pekcgt/idvaey.treFaotlmleonwtignrgouaptlse,aastnd70 allowedtodeliver and rear their offspring until weaning (postpartum day 21). At weaning, 20 Fp,uprsatusn/dseexr/wgernotupawgerroessrpaantdhoomllogyiscealleecxtaemditnoatpiroond.uceThteheFnyegxetnegernaetriaotniorna.tswUenrseelneoctteedxpwoesaendlianfgter weveaalnuiantge.d.TAheaclgieniocafl ppraetphuotliaolgyseepvaarlautaitoinonan(dhevmaagtionlaolgoyp,ecnliinnigcailn cthheemFi)stgreyn,erpaltaisomnaraatnsdwuerrinee. fclyucolreidaendinsPp;ermmalpeasraomneltye)rwsawserceonevdaulucattoeedndiwnetehek1Py0goennetrhaetifoinrs.t A10t Pn;ecrraotpss/syex(P/sgfreoumpa.leEssotrnous `postpartum day 21; Py males after siring lters [approximately 4 months of exposure], Fy `generation at postnatal day 60), reproductive andtargetorgans were weighed and retained for histopathological examination. Histopathological examinationofreproductive organs (testes, epididymides, seminal vesicles, pirmopsatiartee,d arnedpruotdeurcuts,ivoevapreirefso,rmaanndcev.agiLniav)erw,aksidcnoenyd,ucatneddtohnyrloyifdorwePryemparloecsesasneddfaenmdaleevsalwuiatthed ~ `microscopically in 10 randomly selected control and high-dose P males and females, and from all control and high-dose F; males. Thyroid, the only target tissue in Py females, was processed isnubaslleqcuoentnrtollyapnrdohciegsshe-ddoasned Fevaalduualttefdeimnalleos.werTadrogseetgtriosusupessafsrfoemePd;edantod dFeytaenrimmianles2wneor-e.adverse- effect level. At 3500 mg/kg/day, effects considered to be related to H-25231 treatment include: Adverseeffects: Reductions in weekly mean body weights and body weight gains, overall mean body weight gain, weekly mean food consumption and food efficiency, overall food consumption, and overall food efficiencyof Py male rats. Reductions in weekly mean body weight gain and food consumptionof Py female rats during premating (test days 1-8) and on gestation days 0-7 and 7-14. L`oanwd fienmcaildeesnc(seasloivfactliionni)c,awlhsiicghnsowfetroexigecnietryalilnyPyspmoraaldeisc.(lung noise, salivation, stained fur) Reduction in mean pup weight throughout the entire lactation period for F; liters. Reductions in weekly mean body weights, body weight gains, and food consumption, overall --~ body weight gain and food consumption of Fy males. --_-- companSend.Dossntccna TSCACE H25231: One-Generation Reproduction Study in Rats DuPont9763 --~ + Reduction inweeklymean body weights and body weight gains (test days 1-8) of F; females. Inccornesaidseerdedmdeuaentaogreeodfucperedpubtoidayl wseepiagrhattsioanndanbdodvaygwienialghotpegnaiinngduirniFn;grtahtes,pwohsti-cwheawneirneg. period. Potentially adverse, thyroid follicular hypertrophy in Py and Fy males and females. Hepatocellular hypertrophy in the iver in Py males. + Chronic progressive nephropathy in the kidney in Py males. Non-adverse effects: Mihnemiamtoaclridte)carneadsaesssionciraetdedceclhlamnagsessp(arreadmceetllermso(rrpehdocleollgycoaunndt,rehdemcoelgllodibsitnr,ibauntdio/norwidth) in Py males. Increased liver and kidney weights in Py males and females, andliverweights in Fi females. Increased plasma and urine fluoride in P; males, indicating exposure to and metabolism ofa fluoride-containing molecule. --~ At500 mg/kg/day, effects considered to be related to H-25231 treatment include: Adverse effects: Reductions inweekly mean body weightgains, overall weight gain and overall food consumptionofPy males. Potentially adverse, thyroid follicular hypertrophy in Py and Fy males, and P, females. Hepatocellular hypertrophy in the liver in Py males. Chronic progressive nephropathy in the kidney in Py males. Non-adverse effects: . Mihnemiamtoaclritd)ecarnedasaesssioncrieatdecdelclhamnagsess p(arredamceetllermsor(rpehdocleollgycoaunndt,rehdemcoelgllodibsitnr,ibauntdio/norwidth) in Py males Increased liver and kidney weights in Py males, and kidney weights in Py females. + Increased plasma and urine fluoride in Py males, indicating exposure to and metabolism ofa -- fluoride-containing molecule. FS W ------ Company Sanilizad. Doss not contain TSCA CBI H25231: OneGeneration Reproduction Studyi Rats DuPont9763 ~~ AS mg/kg/day, effects considered to be related to H-25231 treatment include: Adverse effects: Potentially adverse, thyroid follicular hypertrophy in Py and Fy males. Non-adverse effects: * Increased liver and kidney weights in Py males. Increased urine fluoride in Py males, indicating exposure to and metabolismof a fluoridecontaining molecule. aUnndde,r trahtes,cobnadsietdioonnsotfhtyrhoiisdsftouldlyi,cualanroh-oybpseerrtvreodp-heyffinecPtylaenvedlF(,NaOdEuLlt)mawlaessnaott>d7e5tmegr/mkign/eddafyo.r Py `The NOEL for reproductive effects was 500 mg/kg/day, based on reductions in mean pup weights throughout the entire lactation period for F; litters at 3500 mg/kg/day. ~~ ~ * tThheotNesOtEsLubfsotrantchieswsetruedynoistddeetfeicnteed.astThheush,igfhoersttidsosseudaty,whthiechNtOoEiLcolisogeiqaulilvyailmepnto0trttahnetNfOfcEtLsaas-idbeufitnaedblby10 the United States Environmental Protection Agency (1985) an fo te no-observed-adverse<fct_ Vel (NOAEL) as define by the European Union (1994). 5 -- `Company Sanitized. Does not contain TSCA CBI H25231: One-Generaton Reproduction Study in Rats DuPon.763 -- INTRODUCTION Th gt substance, 25231, is a Tuorosaractant thatcontains NNT [Rv dose levels for ths study were selected based on the results from a range finding `(s2t0udmygw/iktgh/dHa-y25ac1t5iv6e"iinngrwehdiiecnht)r,at5sw00ermegd/kogs/eddayby(1o0ra0lmgga/vkagg/edawyitahct1i0v0e mingg/rkegdi/ednaty), or C2l0i0ni0camlgs/ikggn/sdoafyt(o4x0ic0imtyg/wkegr/edoabysaecrtvievde iinngerietdhieernmt)alfeosr 4or9 fdaeymsa.lesNoatbaondyydwoesieglhetveel.ffeTchtseroerfore, males exposed to 2000 mg/kg/day had thir dose increased to 5000 mg/kg/day (1000 mg/kg/day a5c0t0i0vem)go/nkgte/sdtadyahya5d2.a 1Ov0e%rdaencraepmpernotxiimnabtoed2y-wweeiegkhtpecroiomdp,atrheedmtaolecosntdroosledanwditwhere sgurbosuepqsuweentrleyssaaccrriiffiicceeddoonntteessttddaayys 6449.aTnhde0r,emreasipneicntgivfeelmy,alaendanldivmera,lkeitdensetys,uabnsdtabnlcoeotdrewaetreed. choilslteocpattehdoflorgoimcatlhley,10w0hialnedli5v0e0r emgn/zkygm/edsaywemraelmeedaossuergerdoiunpst.heTbhleoodl.iveNrsowehirsetoepvaatlhuoaltoegdical cdhoasneggersouipnst.heInliavderdintoirone,lekviadtneedylwieviegrhetnszwyemrees nwoetraeltoebrseed,rvwehdilien tihveer10w0eiogrh5ts00inmtgh/ekg5/0d0ay male mg/kg/day male dose group appeared to be increased. Data are also available from a 45-day range-finding and 90-day gavage study" witha similar -- compound, H-2467, that cc Cn------ thetsheamreanagcet-ifviendineg istundy,-- fats were adminis `1m0y0/0kgm/gd/akyg(/3damyg/(k3g5/0dmagy/akcgt/ivdeayinagcrteidvieenitn)g,re1d0i0enmtg),/kogr/3d0a0y0(m3g0/mkgg//kdga/yd(a1y0a0c0timvge/ikngg/reddaiyenatc)t,ive binogdryedwieeingt)htHs-2a4n6d7r8.eduMcaeldebsoedxypwoesiegdhttog3ai0n00afmtegr/k4gw/edeakysexohfidboisteidngstaantidsttihcearlelfyosriegnhiafdictahnetirlodwoesre lReodwuecrteidotnos2i0n0b0omdgy/wkegi/gdhatyg(a7i0n0(m1g5/%kg--/d2a0y%alctoiwveer) tfhoarnthceonrtermolasi)niwnegre2 waleseokosobsfetrhveedstiundrya.ts e`cxopmopsaerdedtoto10c0onatnrodl1r0at0s0amdgm/ikngi/sdtaeyr.edL1i0v0e0r awenidg3ht0s00w/e2r0e00simgngi/fkigc/andtalyy hHi-g2h4e6r78(.40N%-o4c5o%m)pound- related effects on organ weight were observed in rats administered 10 or 100 mg/kg/day. Iinngtrheed9i0en-td)a,y6s0tmugd/ykwgi/tdhayH-(22406m7g8/,k"gr/adtasyweacrteiveadimnignriedsiteenrte)d, 1o0r 3m0g0/kmgg//dkagy/(d3aymg(/1k0g0/mdga/ykagc/tdiavey afcotoidvecoinngsruemdpitenito)n., Samnadllf,oobduetffsitcatiiesntciycaolclcyusrirgneidfiicnanmtadleecsraedmmeinntisstienrbeodd3y0w0emigg/hktgp/daarya.metKerisd,ney weights weights were were sailgsnoiifniccarnetalsyedinicnretahsee3d0i0nmrgat/skagd/mdianyisfteemraelde6g0romugp/,kwgh/idlaeymHa-l2e4s6i7n8toher 6hi0ghaenrd. Liver 300 mg/kg/day groups had elevatedliverenzymes. "The high-dose level of 3500 mg/kg/day (700 mg/kg/day active ingredient) was selected for this study and is expected to produce toxicity without excessive mortality. This was based on the --_ 2r0es0ul0tsmgo/fktgh/edHa-y2(5410506mrga/nkgge/-dfainydaicntgivset)udyeyt."haRdaats1i0n%thdeechirgehm-ednotsienlbevoedlywweerieghatblwehteontolerate. compared with control when the dose was increased to 5000 mg/kg/day (1000 mg/kg/day active -- -- Fiommany Sanhized. Doss not contain TSCA CBT $2521: OneGeneration Reproduction Study in Rats Duon5763 ~~ ingredient). observed-eff The low doseof 75 ect-level, while the mg/kg/day (15 500 mg/kg/day mg/kg/day activ (100 mg/kg/day e) was expec active) dose ted to be the no- was expected to induce some toxicity. OBJECTIVE Tfuhnectoibojne,ctciovneceopftithoins,sptaurdtuyrwitaisont,oaenvdalguraotwetthh,eaenfdfedcetvoefltohpemteenstt soufbmsatlanecaenodnftehmeagloenadal Crl:CDY(SD)IGS BR rats over one generation. MATERIALS AND METHODS A. Test Substance `Thuetneg .substteasntcseubwsatsanscueppalpipeedabryedthteobsepsotnasbolreasunadetratnhveoco-- RGitionsofthe study. No evidence of instability, such as a change in color or physical state, was observed. B. Test Species --~ On March 5, 2002, daofJtanueary 21, 107 male a 2002 were nd 109 f received emale from Crl:CD Charles (SD) River IGS BR rats, with an assign Laboratories, Inc., Raleigh, ed birth North Cthaerotliimnea-cfoourrusseoe ofnbltohiosdsftluudoyr.inAe,stuhbeseretsouflttshoefsewhainicmhamlsay(2b0epperresseexn)tewderineausseepdafroartearsetpuodryt.of The rat was selected for this study because i is a preferred species for reproductive toxicity teexstteinnsgivaes rbeacckogmrmoeunnddeidnfboyrmthaetigounidieslianveasi.labTlheefrCorml:thCeDli(tSerDa)tuBrRe,stthraeisnuwpaplsicrh,oasnedn pbreecvaiuosues ssutiutdaibelsewrietlhatoitvheetrocloomngpeovuitnyd,shaatrdDiunPesosn,taHnadskienlclidLeanbcoeraotfosrpyo.ntTahniesosutsradiinseiassael.so considered C. Animal Husbandry 1 Housing `inWistthaitnhleesesxcsetepetli,owniorfe-tmheeschohcaabgietsatsiuosnppeenrdieoddsa,baollveatcsagweerboearhdosu.seAdnoinmealperrocoamgse,wseerxees separate, `maintained on a 12-hour light/dark cycle (fluorescent light) and at a temperature of 22 3C and a relative humidity of 50% 20%. Occasional excursions outside the acceptable ranges were `minor and did not affect the study. Rats were housed as breeding pairsduringthe cohabitation period. During the gestation period, --_ f`moamtaeldefreamtaslweesr,eorhaoustehedeinnddiovfidtuhaellcyohuanbtiiltagteisotnatpieornioddayfo2r0.feBmealgeisnnwiintghoountgeevsitdaetinocnedoafy 20 for `Company Sanitized. Does no contain TSCACE -- H25231: One Generation Reproduction Study in Rats DuPont 9763 ~~ copulation, female rats were housed individually in polycarbonate pans with bedding. During the lactation period, adult female rats were housed with their litters in polycarbonate pans. 2. Feed and Water Tap water was provided ad libitum. All rats, except when fasted, were fed PMI Nutrition International, LLC Certified Rodent LabDiet 5002 ad libitum. 3. Identification Prior to assignment to groups, each rat was assigned a temporary cage `Subsequently, an individual identification number was tattooed on the identification. tailofeach rat. The iinndfiovrimdautailonidoennttifhieccataigoen lnaubmelbseirnacslsuidgendetdhetouenaicqhuera6t-.diFgiitgeHnaesrkaetlilonanriatmsalrentuaimnbeedrafatned ltahcetation were tattooed when they were approximate2l1y days old. 4. Health Monitoring Program `fAosllsopweciinfgipedroicnetdhuereHsasakreelpleLrafboorrmaetdorpyerainoidmicaalllhyeatlotehnasnudreenthvaitrocnomnetnatmailnamnotniltevoerlisngarperboeglroawm, the those tht would be expected to impact the scientific integrity of the study: --_ Water samples are analyzed for total bacterial counts, and the presenceofcoliforms, lead, andother contaminants. + Feed samples are analyzed for total bacterial, spore and fungal counts. + Samples from freshly washed cages and cage racks are analyzed to ensure adequate sanitation by the cagewashers. Creerqtuiifrieemdeantnsimaandfneoetd tisouesxecde,egdusatraatnetdemeadxbiymthuemmcaonnucfeancttruartieorntsoomfekeetyscpeocnitfaimeidnannuttsit,iionncalluding sppreecsiefniceedohfeathveysemectoanlts,amaifnlaatnotxsinb,eclholwortihneatmeadxhiymdruomcacrobnocnesn,traantdioonrgstaantoepdhbosypthhaetemsa.nuTfahceturer would not be expected to impact the integrityofthe study. `The animal health and environmental monitoring program is administered by the attending laboratory animal veterinarian. Evaluationofthese data did not indicate any conditions that affected the validity of the study. D. Quarantine and Pretest Period Upon arrival at Haskell Laboratory, the rats were quarantined for 9 days. The rats were observed daily for any clinically apparent signs of disease or injury and weighed 3 times. --_ Orenletahseedbafsriosmofquaacrcaenpttianbeleonbotdesytwdeaiyg-hSt gbayinthsealnadbocrliantiocraylaonbismearvlavteitoenrsi,naalrliasnurdveisviignngeer.ats were Company Sanitized. Does net coentaiTn TSCACB 125231; OneGeneration Reproduction Study i Rats Dupont5763 --_ E. Study Design Treatment Groups and Daily Dosage PGMrouPpNu,mberFemalo GNrumobwer/ DmayilkygiDdoasya)gse Concentration InAgrcetdiiveent __(mglkgiday) m0o v0o 220 70s CWoonw ) 10s vivoo vviioo 220 3550000 (nteurmgedhinte) 710000 @ Weightoftest substance prkgof animal body weight. Generation Py F, Treatment Schedule Approximate Age Approximate Number at Start of Dosing (days) of Study Days Before Mating 55 `Not applicable 70 Not applicable Duration of Dosing Until sacrifice No treatment Sacrifice Schedule -- Animals Schedule Adult Males After siring litters (at discretion of study director) Pregnant Females On day of weaning litters Nonpregnant Females With pregnant females Weanlings All unselected pups will be sacrificed on postnatal day 21 Fy Adults At approximately postnatal day 60 F. Assignment to Groups and Study Start R0atcsofotfroelacahndseexxpweerriemernatnakledgrboyuptsh.eirTmhoesrtarnedcoemnitzlaytrieocnorredseudlfbeoddiynwaediigshttriabnudtironanidnowmhliychastshiegned mean body weights for all groups within a sex were not statistically different (p > 0.05). G. Analytical Methods - Test Substance Administration, Preparation, and Sampling 1. Test substance Administration Tcohnecetnesttrastuibosntsoanfctehweatsesatdmsuibnsitsatnecree.d bAynigmaavlasgeweinreorddoesretdooenncseurdeaidleylifvoerraypopfrokxniomwatnely 70 days -- rsihoorwitnogconhoabeivtiadteinocneoafndcdoupruliantgitohneccoonhtaibniuteadtitoonbpeedrioosde(daufptetort2hweeeeknsd)o.ftPhyemcaolheabaintdatfieomnalpeerriaotds frre ---------------- e `Compe any Sanite ized. Doesnotcontain TSCA CBI H25231: OneGeneration Reproduction Stady in Rats DuPon.9763 ~~ until sacrifice. lactation until Females their pups showing evidence of copulationwere wereweanedon postpartum day 21. dosed throughout Pregnant females gestation and in the process of delivery or showing signs of delivery were not dosed. From gestation day 18 nil delivery, dose Volumes were based on the gestation day 18 body weights. The volume of test substance or vehicle given to cachratwas based on the most recently recorded body weight. Dose volumes were 5 mLkg. Male and female control rats were similarly treated with deionized water at the same dosevolumeas used inthe othergroups. 2. Test Substance Preparation The test substance was a suspension of active ingredient in vehicle (deionized water). The `material was further diluted with vehicle to prepare 3 different concentrations for dosing. `Solutions of the test substance in the vehicle were prepared daily and stored at room temperature until used. The method of mixing the test substance with the vehicle is documented in the study records. 3. Sampling `Samples containing H-25231 at the concentrations of 0, 15, 100, and 700 mg/mL were collected on Test Day 2 for uniformity/concentration verification and 5-hour room temperature stability. Since homogeneity and concentration results for the 15 mg/mL samples were not within acceptable ranges, samples containing H-25231 at the concentration of 15 mg/mL along with a --~ 0 mg/mL control were collected on Test Day 9 for repeat analysis of uniformity/concentation verification and 5-hour room temperature stability. Samples at al concentrations were collected on Test Day 46 and Test Day 114 for concentration verification analysis. All dosing solution samples were collectoend the samedaythe solutions were prepared. The solution vehicle was deionized water. 4. Dosing Solution Treatment Each 1mLdosing sample was diluted in 100mL volumetric with high performance liquid c`mhertohmaantoolg/wraatpehryt(oHfiPnLaCl)cognrcaednetrwaattieorn.s Tofhe0.s0a0m0p4l5e,s0.w0e0r0e5f0u,rotrhe0r.d0i0l0ut5e6dmwgit/hm5L0(:0540:5, 0.50, or 0.56 ppm) H-25231. Prior to this final dilution, each aliquot was corrected with HPLC grade water so that al samples to be analyzed contained an equivalent amount of water. Samples submitted for analysis were analyzed the day the solutions were received. -- -- wm `Company Sanitized.Does not contain TSCACBI 25231: OneGeneration Reproduction Stdy inRats DuPon.9763 ~~ 5. Chromatographic Conditions LC/MS Method Method (Test Day 2/9) `HPLC Instrument: MS Instrument Hewlett-Packard Model 1100 HPLC Micromass Quattro LC MS with "Z-spray" electrospray LCpoCalruammne:ters: XTerraMS C18, 2.1mm x 30mm Mobile Phase (Time Table), flow rate: 0.00 minutes: 50% methanol/50% 10 mM Ammonium Acetate, 0.25 mL/min. 10.00 minutes: 100% methanol/0% 10 mM Ammonium Acetate, 0.25 mL/min. 16.00 minutes: 100% methanol/0% 10 mM Ammonium Acetate, 0.25 mL/min. 16.01 minutes: 50% methanol/50% 10 mM Ammonium Acetate, 0.30 mL/min. 23.00minutes: 50% methanol/50% 10 mM Ammonium Acetate, 0.30 mL/min. Run Time: 23.0 minutes Flow rate: (noted above with mobile phase) Injection Volume: 20 microliter Oven Temperature: 35C --~ MTpSoanrizaamtieotnemrosde:: Electrospray (ESI), negative ions Capillary voltage: 20kV Cone Voltage: av `Source Temperature: 120 Desolvation Temperature: ~~ 300 Sean function: SIR: 789, 889, 989, and 1089 mz time: 0-16 minutes --~ Tm Company Sanitized. Does not contain TSCA CBI --~ ~ ~ 125231:One.Generation Reproduction Study in Rats DuPont9763 LC/MS Method Method (Test Day 47/114) HPLC Instrument: MS Instrument Waters Model 2790 HPLC Micromass Quattro Micro LC MS with "Z-spray" electrospray LC parameters: Columns: XTerraMS C18, 2.1mm x 30mm and Phenomenex MercuryMS Luna C18 (2), 2.0mm x 20mm Mobile Phase (Time 0.00 minutes: Table), flow rate: 50% methanol/50% 10 mM Ammonium Acetate, 0.25 mL/min. 8.00 minutes: 9.00 minutes: 100% methanol/0% 10 mM Ammonium Acetate, 100% methanol/0% 10 mM Ammonium Acetate, 0.25 mL/min. 0.25 mL/min. 9.10 minutes: 12.00 minutes: 100% 100% methanol/0% methanol/0% 10 10 mM mM Ammonium Ammonium Acetate, Acetate, 0.40 0.50 mL/min. mL/min. 12.10minutes: 50% 18.00minutes: 50% methanol/50% methanol/50% 10 10 mM mM Ammonium Ammonium Acetate, Acetate, 0.40 0.25 mL/min. mL/min. Run Time: 18.0 minutes Flow rate: (noted above with mobile phase) Injection Volume: 20 microliter Oven Temperature: 35C MS parameters: Tonization mode: Electrospray (ESD), negative ions Capillary voltage: 35kV Cone Voltage: 40V Source Temperature: 150 Desolvation Temperature: ~~ 300 Scan function: SIR: 789, 889, 989, and 1089 m/z time: 0-10 minutes 6. Calibration and Quantitation Arefsetroecnkces)olwuatsiomnaodfethien HH-P2L52C31gratedset mwaatteerr.ialAp(psreopparraitaetesaamlpilqueostsooffHt-h2e52s3t1o,ckuwseerdeasdialnuatleydtiwciatlh - 5th0e:5d0osmientghasnaomlp/lweastewroualftderbae cmoarirnetcatiinonedwiintheaHcPhLdCilugtreaddsetwaandtaerrd.soTthheatseansoalmuotuionntsewqeurievaulseendt taos calibration standards that bracketed the target concentration of the diluted dosing samples. Mass tsoelcehctairvgeeiroantimoo(nmitzo)rifnrgomofLtCh/esMeSstaannadlaysridss uosvienrgtnheegmaatsivseriaonngeeloefct7r8o9sptroay1i0o8n9iz(amt/izon=a7n8d9, 889, 9`8A9p,pe1n0d8i9x)Aw,eFrieguurseed1ato--co1ndstforrucrtepcraelsiebnrtaattiiovneccuarlviebsrabtyiotnhceuarvpepsr)o.priMaetaesruergeredsscioonnce(nstereations for dosing solutions were determined by applying the peak area from replicate injections of the -- = Compary Sanitized. Dos not e~-tain TSCA CBI Company Sanilized. Daas nat mmtain vans ~nr H25231:OneGeneration Reproduction Study in Rats DuPont9763 -- samples to each calibration curve. The mean result from the concentrations at al selected mlz (n= 4) is reported astheconcentration for the sample. T(eCs.tV.su=bssttaanndcaerudndiefvoiramtiitoyni/nmtehaenvxeh1i0c0l)e owfatsheevmaelauastuerdedbycocnaclecnutlraattiinogntsheincodeufpfliicciaetnetsoafmvpalreisatfioorn eatacHhasdkoeslilnLgalbeovrela.toArycfooerffaicccieepnttaobflevadriisattriiobnutoifonloefsts htheenteosrt seuqbusatlatnoce1t0h%roiusgthhoeustttahnedasrodluctriiotne.rion Hanoawleyvsiesr,hiafstshheotwenstvsauribasbtialnictye,haascobeeffeincisehnotwgnreatotebretdhiafnfi1cu0lmt atoydbiespaecrcseeptianbtlhee. vehicle or the Tcohnecemnetarantiroensuoltfotfhethteesdtuspulbisctaatencseafmoprltehsefroersepaeccthidveosdionsginlgevleelvewlass. used to determine the Svtearbiifliictaytiwoansasevtahleubaatseedlibnyeufsoirncgotmhpeamreinagntrheesuclotrorfestpheondduipnlgicsattaebisliatmyprleessulftsr.om the concentration H. Body Weights -- Py Rats 1. Premating Feeding Period --_ All Py rats were weighed once per week. 2. Gestation and Lactation Periods Py female rats were weighed on days 0, 7, 14, and 21 ofeach period. Female rats without evidence of copulation, that copulated and did not deliver a liter, and male: fats continued to be weighed on a weekly schedule. L Food Consumption and Food Efficiency-- Py Rats 1 Premating and Cohabitation Dosing Periods i(rnedpiovritdeudalufpotoodtcesotndsauymp7t1i).onEwaacshdfeeteedremriwnaesd wweeiegkhleydthatrotuhgehboeugtitnhneinpgerainodd,eennddionfgthteesitndtearyva7l5 a1nsd tshuebtfriancaltewdeifgrhotmotfhethienitfieaeldefreeadnedr twehiegahmt.ouFnrtoomf stphielflaogoedfcroonmsutmheptfieoendearnddurbiondgytwheeiignhtterdvaatla, `he mean daily food efficiency was calculated food consumption was not determined during cohabitation 2. Gestation and Lactation Periods -- d11.iviEdaucahlffeoeodedrcwoanssuwmepitgihoendoaftptrheegbneagnitnPn;infgemaanldesenwdasofrtehceoridnteedrvoanl gaensdtatthieonfidnaalyswe0i,g7h,t1o4f, athned eeder and the amount of spillage from the feeder during the interval was subtracted from the rei --=-- Company Sani--tzed-- : Doe-- snot-- conta--in T--s cy 125231: One Generation Reproduction Study in Rats Dupon763 ~ initial feeder weight. From the food consumption and body weight data, the mean daly food efficiency was calculated. Food consumption was not measured for females without evidenceofcopulation and for males. Food consumption was not measured during lactation. J. Detailed Clinical Observations and Mortality~ Py Rats Cage-site examinations were conducted at least once daily throughout the study. At least once weekly throughout the premating feeding, gestation, and lactation periods, each of the P, parental ats were individually handled and carefully examined for abnormal behavior and/or appearance. K. Estrous Cycle Evaluation Vaginal lavage samples were collected daily from al P, female ras in order to determine the stagesofthe estrous cycle. Vaginal lavage samples were collected beginning 3 weeks prior 0 mating, and continuing until copulation was confirmed, or the cohabitation period ended. Vaginal lavage samples were collected from all Py parenial femal rats at the ime of sacrifice. Vaginal lavage samples were examined microscopically for determination of the stage of the estrous cycle (diestrus, estrus, proestrus). --~ L. Breeding 1 StartofCohabitation Mier 2 weofeexpkosusre to the test substance 2. Durationof Cohabitation Period nil evidence ofcopulation was observed (designated as day 0 of gestation), or 2 weeks had dapsed. 3. Cohousing fach female was continually housed on a 1:1 basis with a randomly selected, nonsibling male of fnesfsearmreeddobsaacgketloevienld,iivnidtuhaelmcaalge'eshcoaugsei.ng.On the day copulation was confirmed, the female was 4. EvidenceofCopulation travaginal copulation plugorsperm in vaginal lavage sample. Vaginal lavage samples were. |ledectteerdmidnaeiliyffthreorme awlalsPyspfeemramlperreastesntthiant tdhied vnaogtinhaa.veVaangiinnatlralvaavgiangaelscaomppulleastiwoenrpelcuogllinecotredder ring cohabitation and continued until evidence ofcopulation was observed or the cohabitation --_ priod ended. 24 Company Sanniiz,ed. Doos not contain TCA Cy || 125231:OneGeneration Reproduction Study in Rts Dupont9763 --~ M. Gestation Procedures Afier being transferred into polycarbonate pans (on day 20 of gestation for mated females, or at the end of the cohabitation period for females without evidence of copulation), female rats were observed at least twice daily for signs of delivery and offspring. N. Lactation Procedures `The day when delivery was complete was designated day 0 postpartum. At eachexamination period, offspring were individually handled and examined for abnormal behavior and appearance; any dead, missing, or abnormal pups were recorded. 1. Day0 Postpartum Live and dead pups in each litter were counted as s00n as possible after delivery was completed. Live pups in each litte were individually weighed. 2. Day4 Postpartum Litters were culled randomly to 8 (4/sex when possible). Extra offspring were euthanized (by decapitation) and discarded without pathological examination. Litters of 8 offspringo fewer were not reduced. Litter countsweredetermined priooanrdafter culling. Individual pup weights were determined prior to culling. --_ 3. Days7and 14 Postpartum Pups in each litter were counted by sex and individually weighed. 4. Day2l Postpartum (Weaning) Pups in each liter were counted by sex and individually weighed. Randomly selected weanlings (onelsexdliter) were placed in individual cages and monitored for attainmentofdevelopmental Iandmarks. All unselected pups were then sacrificed and subjected to a gross pathological examination. O. Fy Generation 1. Body Weight Measurements All ats were weighed weekly until termination (proximately postnatal day 60). Rats were also `weighed on the dayofpreputial separation or vaginal opening. 2. Food Consumption and Food Efficiency Individual food consumption was determined weekly until termination (approxima1tye postnatal --~ odfayth6e0f)e.edEearcahnfdeetdheerawmaosunwteoifgshpeidllatagtehefbreogmitnhneinfgeeadnedr deunrdionfg tthhee iinntteerrvvaall awnads tshuebtfsi-naaeltewdeifgrhotm = `Company Sanitized. Does no! contain TSCA Cal H25231:OneGeneration Reproduction Study in Rats Dupont5763 --~ the initial feeder weight. From these determinations and body weight data, individual daily food `consumption and food efficiency were calculated. 3. Clinical Observations Cinadgiev-isdiutaelelyxahmainndalteidoansndwecarreefcuolnldyuecxtaemdianteldeafsotroanbcneodramilayl. beAhtavleiaosrtaonndc/eorweapepkelayracnacceh.rat was P. Developmental Landmarks Dmoenvietloorpemdenotnala dlaainldymbaarskiss innttlhecrFiytegreinoenrawtaisonacmhaileeveadn.dAfneimmaalelsrawtesr(eonaellssoexw/eliitgehre)dwoenrethe day the developmental landmark was achieved. 1. Vaginal Patency Female rats were examined once daily beginning on postnatal day 21 until achievement or postnatal day 43, whichever came first. 2. Preputial Separation Male rats were examined beginning on postnatal day 35 until achievement or postnatal day 55, -- whichever came first Q Clinical Pathology Evaluation A clinical pathology evaluation was conducted on week 10 prior to cohabitation on the first s1a0mrpaltess/sfeoxr/gtrheoucplidneiscialgnpaattehdofloorgytheevarleupartoidounc,titvhee emvaalleuartaitosn.weTrehepldaacyedbeifnomreetcaoblolelcitsimoncoafgebsl.ood The male rats were fasted overnight (approximately 16 hours) and urine was collected from cach rat. Females were fasted, but were not placed in metabolism cages, and urine was not collected. Borlboiotadlssaimnupsloefscfaocrhheamnaitmoallogwyhialnedtsheeraunimmcahlewmiasstruyndmeerasliugrhetmceanrtbsonwedrioexciodleleacntesetdhfesrioam. thBelood samples for fluoride analysis were collected at sacrifice from the abdominal vena cava of male rats onlywhilethe animal was under carbon dioxide anesthesia. 1. Hematology Blood samples were evaluated for quality by visual examination prior to analysis. Complete banlaoloydzecro,unotrs,deitnecrlmuidniendg rfertoimcumloiccyrtoessc,owpeirceevdaeltueartmiionneodfotnheabBlaoyoedrsmAedavr.iaWr1i2g0hhte-smtaationleodgyblood samnedaervsalfuraotmioanlloafnciemlallulsarwemroerpehxoalmoigyn.ed Bmlicoroodscsompeiacrasl,lsytafiornecdonwfiitrhmnateiwonmoeftahyulteonmeatbleude,rewseulrtes --_ pevraelpuaarteidonf.roBmoenaechmaarnriomawlsumnedaerrsgwoeirneg aprheepmaarteodlaotgtyheevfailnuaaltsiaocnr,ifbiucte wferroemnaolltsnuerevdievdinfgoranimals. -- wm Company Sanitized. Doesnot contain TSCA CB 25231:OneGeneration Reproduction Stdy in Rats DuPon.9763 -- `Bone marrow smears were stained with Wright's sain and coverslipped, but analysis was not necessary to support experimental findings. The following hematology parameters were determined: red blood cell count hemoglobin hematocrit `mean corpuscular volume `mean corpuscular hemoglobin `mean corpuscular hemoglobin concentration red cell distribution width absolute reticulocyte count platelet count white blood cell count differential white blood cell count `microscopic blood smear examination 2. Serum Chemistry 7`S1e7ruclmincilcianliccahlecmhiesmtirsytraynaplayzrearm.etPerlsaswmeareflmueoraisduersewdeorne daeRtoecrmhienDeidaugsnionsgti&csO(1B2MpCH)mHeittearchaind a fluoride-selecive electrode. The following serum and plasma clinical chemistry parameters were determined: --~ aspartate aminotransferase: alanine aminotransferase sorbitol dehydrogenase `plasma fluoride 3. Urinalysis `Urine volume was measured. Urine fluorides were determined using a 12 pH meter and a fluoride-selective electrode. `The following urinalysis parameter was determined: urine fluoride. R. Anatomic Pathology Lo PyAdults SAulbljPeyctpeadretnotgarlorsastspawtehroelosgaiccrailfiecxeadmbiynactairobno,nidnicolxuiddiengastphhoysxeifaotriownhiacnhd meaxtsainngguidnidatniootn,reasnuldt in the production of offspring. The uteri of all cohabited females were examined for the presence. --~ `and number of implantation sites. 27 Company Sanitzed. Does notcontain TSCA CBI H-25231: OneGeneration Reproduction Study in Rats Dupon.763 ~~ `The following table lists tissues that were weighed and/or collected from P adults: Tissues Weighed from P; Adults Male Female othSexes Testes Uterus (with Thyroid Gland* Epididymides oviducts and cervix) Liver Seminal Vesicles (with~~ Ovaries Brain Coagulating glands) Kidney Prostate EE `Tissues Collected from P, Adults Male Female BothSexes Testes" Ovaries `Thyroid Gland* PrEopsitdaitdeymides Uotveirdusuc(twsit)h cervix and ~~ GPirtousistaOrbysGelravnadtions Seminal Vesicles (with Vagina Liver Coagulating Gland) Kidney -- ba ThTyhreoriigdhtgleatndsswaenrdeepwidiedyimiasfgcelrhlfcitexeadtdiofnom male rats were placed in Bovin' souton. The ef testis caonldleecptieddifdyrmoimsmwaelreeafnrdofzeemafloresapserwmearsesepslsamceendti.n fAolrmaolbien,r tissues (reproductive andnonreproductive) wGreorsesgelneseiroanlslyobostercvoeldleacttende.cropsy for wich histopathology was not pproprise of would otbeadditive 2. Offspring wOfaflsupartiinogn.that were found dead during the lactation period underwent a gross pathological 3. Fi Weanlings mMldeunrsweelencattegdropsuspsp,atlihtotleorgsiiczaelpeevramliutatitnigo,n woenrpeosstancartifailcdedayby21c.arGbroonssdiloexsiidoensaswpehryexiparteisoenrvaendd. 4 Fads : cMeIiFvegdenaegrraotsisonparatthsolwoegriecaslaecrxiafmiicneadtbiyonc,aribncolnuddiionxgiFdyeraastpshtyhxaitadtiieodn (afnodunexdsdaenagdu,inaactciiodne,ntaanldly sililoend)sowrerweerperesascerrivfeidceidn ianpperxotprreimaitsepfriixoartitvoepfoosrtnpaotsaslibdlaeyf6u0t.ureSehliescttoepdatthioslsougeiscaanldexaallmignraotsison. -- ' | % -- `Company Sanitized. Does not contain TSCA CBI | H25231: One-Generaton Reproduction Study in Rats DuPont9763 --~ `The following tables lists tissues that were collected and/or weighed from Fi adults: `Tissues Weighed from F; Adults Male Female Testes Uterus (with oviducts and Epididymides cervix) Seminal Vesicles (with ~~ Ovaries Coagulating glands) Prostate BothSexes Thyroid Gland Liver Brain Kidney `Tissues Collected from Fy Adults Male Female Testes" Ovaries `Thyroid Gland EPproisdtiadtyemides" Uotveirudsuc(twist)h cervix and GPirtousistaOrbysGelravnadtions Seminal Vesicles (with ~~ Vagina Liver Coagulating Gland) Kidney ab TThhyeroteisdtegslaannddsewpeirdiedwyemiigdheesdwarteeplvaacteidoinn Bouin's solution. Alother tissues (eproductve and non- '--_ Grreporsosdulcetsiivoen)s ocoblsleercvteedd artonmecmraoplseyafnodrfwehmiaclhehriatsstowpeatrhoplloagcyewdansfnoortmaalpipnr.opiate of would notbeadditive wee generally not collected 5. Microscopic Evaluations - P; and Fy Rats Histopathological examination of reproductive organs (estes, epididymides, seminal vesicles, prostate, and uterus, ovaries, and vagina) was conducted only for Py males and females with impaired reproductive performance. Gross lesions were saved and evaluated microscopically if they might have been additive to the interpretationsofthe study. Selected gross observations for which a microscopic diagnosis would not be additive (e.g., osteoarthritis, pododermaids, tal chronic dermatitis, calculus, and deformities of the teeth, oe, ai, or ar pinnae) were saved, but not processed for microscopic evaluation. Liver, kidney, and thyroid were processed and evaluated microscopically in 10 randomly selected control and high-dose male and female Py rats, and from all Fy control and high-dose adult males. Thyroid, the only target tissue in Py females, was processed in all control and high-dose F, adult females. Target tissues from Py and Fi animals were subsequently processed and evaluated in lower dose groups as needed to determine a no-adverse-effect level. Selected tissues representing gross lesions from 3 Fy Weanlings were also processed and valuated microscopically. --- ss Company Sanitized. Doe not contain TSCA CBI H25231: OneGeneration Reproduction Study i Rats DuPont9763 ~ S. Sperm Assessment Sperm parameters for all Py parental males were evaluated. The right epididymis was removed and weighed. The right cauda epididymis was weighed, excised, and placed in 32C phosphate buffered saline with 10 mg/mL bovine serum albumin, pricked with a needle to facilitate the release of sperm, and placed in an incubator at 32C for 5 minutes. After incubation, an aliquot was placed in a sample chamber which was loaded into a Hamilton Thome Integrated Visoal Optical System (IVOS). The percentage of motile cells among at least 200 cells examined per animal were determined. After removalofan aliquot of sampling for videotaping, the right cauda epididymis was further incubated for approximately 15 minutes. An aliquot was stained with eosin, and smears were prepared on microscope slides. Spermsmearswere examinedtodetermine thefrequency of `morphologically abnormal sperm, expressed as percentageofnormal cells among at least 200 cells examined per animal. The specific types of abnormal morphologies, if an, were not categorized. The excised right cauda and the right caput and corpus epididymis were then placed in Bouin's solution. `The left epididymis and left tests, following removal, were flash frozen in liquid nitrogen and stored at --65 to ~85C until analyzed. After thawing, the cauda epididymis wasexcised, weighed, and homogenized. After thawing, the tests was weighed and homogenizde. Sperm ~ cpeorugnrtapmetrecsatuidsaweeprieddiedtyemrimsianneddpuesringgrathmecIaVuOdSa.epididymis, and spermatid count per testis and --~ Company Sanilized. Does not contain TSCA Cywapany1 Seized. Doesntotaa Tsca om H25231:One.Generation Reproduction Study in Rats -- Dupo 9763 T. Statistical Analyses "The following table lists the indices of reproductive function that were calculated for the Py and Fy adults. `Reproductive Function Calculations Mating Index (%) = Number Copulated 100 Number Cohabited Fertlitylndex (%) = Number Pregnant) x100 Number Copulateda Number ofLitters with GestationIndex (%) ~~ = atLeast One Live Pup x100 NumberofLitters Implantation Efficiency (%) = Number of Pups Bom x100 Number of Implantation Sites. Pups Bom Alive (%)c = NumberofPu live x100 --_ NumberofPups Bor ViabilityIndex (%)c:d = NumberofPupsAliveDay4Preculling x 100 Number of pups born alive Number of pups alive Lactation Index (%)6d = awt ea(Dany21ipostnpartgum) x100 Number of pups alive Day 4 Posteulling LitterSurvival (%)d ~~ = N Numbu erom offlviitb taebrlsee wleitatr neresddelivered x 100 a pErevgain,doofrecdoepnluilvacetriyoenof=a mtecra.vaginal copulatory plug, sperm in vaginal lavage sample, found dead b & Including those found Tobedeterminedfo cdaecahdlperre.gnaMnetadnurinndg sgteastnadtairodn.deviation frcach dose level will be calculated. @ Excluding liters sacrificed duetodeaoftdahm during lactation. - -- EN SE - Company Sanitized. Dossnotcontain TSCA CBI H:25231: One-Genesation Reproduction Study in Rats DuPont9763 Pu Statistical Methods Er lieetdsoSnott |apsrli mi st Pune Psiminary Tet sitcan mitcn, Body Weight Test forlackof rend | `oSeqfuetnhteiaJlonaepkplhieceartei,on"|Prlilimmii nry testfosr BodyWeightGain Terpstra trend test | PAITISe com |FGpoeiosadtiiCaooinnsonunmgpSttihioNnumbers-- ow PieMmepciaannNiBauiomorenrEAflocifivPeepncsyPe Lite ----_ PSmeiipwmapiSenyprgion Shhoampoirgo:e-nWiilnktaneds for ||oO4t80r5"e40o0 D!UIS || 1Kruspkaly-Walelistst LL0i:at4ceDariySounrVvdiivesalxiy normaly" Organ Weight - Greve Aaa Vac Rood Bifchesy ~~ (Cia Patol Tebesnie sioo mViot 4ne vaOnree-iwaaeyffosolrlalllonoywwseiedsdowfw_ii|tthh|DunnKfeotrltl'uoswsetpdeasWwotai'lltvhlDuentaoso NdangcIndoefxChm Oras| {GVFeeristialbiitoynIiIndonedxne.s None Cochran-Armitage test for trend" MeCanoPovp Waeighss ssci)| Nowe Liewconst ofleant| pr th |VSaexgRiattioF. rey = (covariates: body weigh) `Shapiro-Wilk test for Analysis of DumetcHsu ovr: body Preputial Separation weigh) `normality `covariance? + PshaiecviSashea.cpompWailrkoncsstanostssiignidficparnetloimtinLareyvoesn ertoi ysciogdsa hbuesttvterosironocf:kDofuvenndecss will bed 4 IBeAfstorhcsepgtiunoiicniecdecrnoaceneelgcisteeinoxonnptlsswoisgauniiodfsn.i)cda.ntt, but a significant lackoffit occurs, then Fisher's Exact test" with a determin ich vais (dy weight parses) i diontodose -- Company Sanitized. Doesnot contain TSCA CBJ F-25231: OnGeeneration Reproduction Study in Rats DuPont9763 ~ sFiogrniefaicchanptadroasmee-treerspaonnasleyzweadswidtethecatterde,nddatteastf,rtohme test the twoapsdoapspelgierdoutpo wthaesdeaxtcalsuedqeudenatinadlltyh.e If a test arfefpeecatteeddfuenttuislensopesriglniitftiercaonrttthreenlditwerasmedaetnewctaesd.u"seFdoars ltihtteerexppaerraimmeetnetrasl, tuhneitprfoorposrttatiiosntiocfal euvseadl,uaatnidoont.h"erTphaeralmeevteelorsfsainganilfyizceaandc,se dseeleemcetdedniescpes<s0a.r0y.5. Additional statistical tests were `Where the data were tied and the standard large sample version of Jonckheere's test was not `applicable, exact p values were calculated using permutation methodolog*y. RECORDS AND SAMPLE STORAGE Laboratory-specific or site-specific raw data, such as personnel files and equipment records will be retained by the facility where the work was done. A sampleofthe test substance was collected for archive purposes and retained at Haskell Laboratory. Specimens, raw data,and the final report will be retained at Haskell Laboratory, Newark, Delaware, or at Iron Mountain Records Management, Wilmington, Delaware. Raw data will be retained at Haskell Laboratory, Newark, Delaware. Characterization data (percent purity, composition, and known impurities) wil be stored at Regional Analytical Services (RAS), Jackson Laboratories, Deepwater, New Jersey. Characterization data used to support test substance stability will be retained at Haskell Laboratory, Newark, Delaware, or at Iron Mountain m~ Records Management, Wilmington, Delaware. --~ wm -- Company Sanitzed. Does no contain TSCA Cat H25231: OneGeneration Reproduction Study in Rats --_ DuPont9763 --_ RESULTS AND DISCUSSION --~ E -- Company Sanitized. DoesnotcontainTSCA CBI H-25231; One-Generaion Reproduction Study in Rats ~~ ANALYTICAL DuPont9763 A. Chromatography (Appendix A) H-25231 eluted from the HPLC column as resolved peaks over mass to charge ratio (m/z) range of approximately 789 to 1089. For the: of quantitation, the mz ratigs of 789, 889, 989, 1089 for the "bis" substituted component ere determined to be representativeofthe H-25231 in the dosing matrix. Representative LC/MS chromatograms are shown in Appendix A, Figures 2(a - ). Test substance was not detected in the 0 mg/mL control. B. Dosing Solution Analyses (Table 1, Appendix A) 1. Concentration Verification and Stability Samples Analytical results from dosing solutions prepared Test Day 2 and Test Day 9 (15.0 mg/mL, only) analyzed for uniformitylconcentration verification and stability are shown in Summary Table 1 and Appendix A, Table I. ~ `The following table summarizes the results for uniformity/concentration verification and stability analysesforthe H-25231 sample preparation on Test Days 2 and 9. Preparation Nominal' Measured" Average CV Stability" Day mgml mgmL % % % Nominal Nominal TestDay2 11050 897146197228 720 944 27 4 720 817 00 715,668 988 5 1084 TestDay9 1s 127%156 947 14 1100 a DHosinsgsolutrioin coencentragon-- mgH-2523 mL based on ml.dose volume. b DStuapbliilciatytesasmapmlpelsesbaenlalfor hours at room temperature. Percent Nominal based on measured. 4 RReeppoorrtteedd rreessuulltt bbaasseeddoonndaulpllaincaaltyesirseafnraolmytsihsoofrtihgionralgisnaaplss.ample. `The results for H-25231 samples prepared on Test Day 2, show tha the test substance was adequately mixed (CV's less than 10) except at the 15 mg/mL level (CV = 27), at the targeted levels (target = & 5.6% of nominal) except for the 15 mg/mL level (72% of nominal), and stable: in the vehicle when held 5 hours at room temperature. An additional sample of the 15 mg/mL. ~~ level was taken on Test Day 9 for repeat analysis since the results for the Test Day 2 sample did TE Company Sanktized. Doesnot contain TSCA-- CBI H:25231: OneGeneration Reproduction Study n Rs DuPont9763 ~ pnroetpamreeedtocnoncTeensttrDataiyon9oafntdhheom1o5gmenge/imtLy alcevceelp,tasbhioliwtythcarittetrhiea.tesTthseubrsetsualntcsefworasH-a2d5eq2u3a1teslaymple mwihxeendh(elCdV5=ho14u)r,saatttrhoeotmartgeemtpeedrlaetvuerles.(tTaersgetts=ubst5a.n3ce% wofasnonmoitnadle)t,ecatnedd isntatblhe0einmtgh/emveLhicle samples. 2. Concentration Verification Samples AcnoanlcyetnitcraaltiroensuvletrsiffircoamtidonosairnegsshoolwutnioinnsSpurmepmaarreyd TTeasbtleDa1ya4nd6 AapnpdeTnedsitxDAa,yT1a1b4leanILd analyzed for The following table summarizes the results for concentration verification analyses for the Test Days 46 and 114 of the H-25231 sample preparation. Preparation Nominal" Day mg/mL Measured mg/mL Average CV %Nominal __% Test Day46 15 100 151,166 1060 7 12,113 1130 1 700 749, 666 1011 8 TestDayll4 15 100 165,125 107, 120 980 17 1140 8 --_ 700 765, 681 103.3 8 o D2os5i2n3gs1oliustaipopnrcooxnicmeatnetlryaggnmg H-2523/mlged on midosevolume. b RDuepploirctaetderseasumlptlbeasspeedroenvedlupwliecraeteanraleyazenda.lC.yVo-fstihcsalocruilgaitneadl s0amvpelref.y uniformity ofmixiue. "aTdheequraestuelltys mfiorxesadmepxlceesptprfeopratrheed1o5n mTges/tmDLalyesve4l6oannTdes1t14Dainydi1c1a4tewthhiacththweatsesmtasrugbisntaalncaendwaatsthe targeted levels (targe=t 14.0% of nominal) for all H-25231 samples. Test substance was not detected in the 0 mg/mL sample. C. Analytical Conclusions Rteesstulstusbsftraoncmethweasanmaliyxseids opfrotpheerlteystexscuebpsttafnocretdheos1i5ngmsgo/lmutLiolnesvedluroinnTgetshteDsatuyd2y ibnudtiwcaast.e that the aecxcceeppttafbolretohne T1e5stmgD/amyL9,l4ev6e,laonndTmeasrtgiDnaayll2yaanccdespttaabblleeuonndeTresttheDcaoynd1i1t4i,oans tohfetthaersgteutdeyd.leTveeslts sbeulbisetvaendcetowahsavneoitmfpoaucntdedintthhees0tumdyg/simnLcesathmeplreesp.eatThseamrpelsiulntgsoonbtTaeisntedDaoyn T9easntdDsauybs2eaqrueenntot samplings showed acceptable results. --~ `Company Saniizec. Doss notcontain Tc car Tw -- -- - Pe -- H25231 OneGenerationReproduStcudtyiinoRatns Duont763 REPRODUCTIVE TOXICITY EVALUATIONS IN-LIFE TOXICOLOGY A. Py Rat-s Mean Body Weights and Body Weight Gains 1 Pj Males: (Tables 2-3, Appendices B-C) `There were test substance-related reductions in body weights at 3500 mg/kg/day and body weight gains at 2500 mg/kg/day. At 3500 mg/kg/day, mean body weight gain was reduced for much of the dosing period. As a result, weekly mean body weights were consistently reduced throughout the dosing period, and mean final body weight (test day 113) and overall weight gain (test days 1-113) were 80%and64%ofthe control mean, respectively. At 500 mg/kg/day, there were transient reductions in body weight gain; the most evidentofthese occurred on test days 1-8, 1522,43-50, 85-92, and 92-99. As a result, mean finalbodyweight (test day 113) and overall `weight gain (test days 1-113) were 94% and 88% of the control mean, respectively. 2. Py Females: (Tables 4-9, Appendices D-G) `wTehiegrhetwgearien tweastssrubesdtuacnecde-druerliantgedprreemdautcitnigo,nsoinntbesotddyawyesig1-h8t agnadina36t-4335,0a0ndmgo/nkgg/edsatya.tioMnedaanysb0o-d7y and7-14. These sporadic reductions in weight gain did not affect overall weight gain during premating (95% of control mean on test days 1-71) or gestation (95% of control mean on gestation days 0-21). Overall mean body weight gain during lactation was increased at 3500 mg/kg/day (226%ofcontrol mean on lactation days 0-21) and was mainly due to a mean body weight change that was 165%ofcontrol on lactation days 14-21. This finding was considered spurious and not biologically meaningful. B. P; Rats - Food Consumption and Food Efficiency 1 Py Males: (Tables 10-11, Appendix H) `There were test substance-related reductions in food consumption and food efficiency at 3500 mg/kg/day. Mean food consumption was reduced (89%-98% of the control mean) for `much of the premating period. As a result, overall food consumption for this period (test days 1- 71) was 93% of the control mean. Mean food efficiency was reduced (89%-98% of the control mean) for muchofthe premating period. As aresult, overall food consumption for this period (test days 1-71) was 93% of the control mean. 57 Gopi Banilzed. Dos not containTSCA GBI 125231: One Generation Reproduction Study in Ras Dupont9763 ~ 2. Pi Females (Tables 12-15, Appendices 1-1) There were test substance-related reductions in food consumption at 3500 mg/kg/day. Mean food consumption was reduced during premating, on test days 1-8, and on gestation days 0-7 and 7-14. These sporadic reductions in food consumption did not affect overall food consumption during premating (98% of control mean on test days 1-or7ges1tat) ion (93%ofcontrol mean on gestation days 0-21). C. Py Rat-s Clinical Observations and Mortality 1 Py Males: (Table 16, Appendix K) `There was no test substance-related mortality. Two animals died as a result of gavage trauma; one in the 3500 mg/kg/daygroupon testday42 and one in the 500 mg/kg/daygroup on test day 86. One animal in the 3500 mg/kg/day group was found dead on test day 66. This death was considered possibly due to gavage trauma since the lungs had red discoloration and congestion, and prior to sacrifice this animal did not display any significant reduction in body weight gain or food consumption, or show any overt signs of toxicity except for intermittent salvation. One animal in the control group was sacrificed in extremis on test day 60; prior to sacrifice this animal displayed reduced body weight gain andbody weight loss as a resultof a sore on -- shoulders/neck. There were test substance-related clinical observations at 3500 mg/kg/day that consisted of low. igennceirdaelnlcyesspoofra"dliucn.g nTohieses,a"li"vsaatliiovnatoicocn,u"rr"esdtaaifnteedr dnoossie,n"g aanndd "wsatsainnoetd cpoenrsiindeeurme,d"iwnhdiiccahtiwveeroef neurological effects since previous studies with ths active ingredient showed no signs of neurotoxicity. 2 Py Females: (Tables 17-19, Appendices L-N) `There was no mortality at any dose level. There were test substance-related clinical observations during premating at 3500 mg/kg/day that consisted of low incidences of sporadic salivation. `There were no test substance-related clinical observations during gestation or lactation at any dose level. The salivation occurred after dosing and was not considered indicative of neurological effects since previous studies with this active ingredient showed no signs of neurotoxicity. -- `Company Saniizsd. Dose not contain TSCA CBI ---------------- H:25231: OneGeneration ReproductionStudy in Rats DuPont9763 -- D. Sperm Parameters (Table 20, Appendices 0-Q) `There were no test substance-relatedeffectson sperm motility, morphology, epididymal sperm or testicular spermatid numbers at any dose level. The percent normal sperm was statistically significantly reduced at S00 and 3500 mg/kg/day (98.3% and 98.3% vs. 99.1% for the control group). These changes were considered spurious dtuotheeir small magnitude and values were within the historical control range at Haskell Laboratory. Historieal Control Data for Haskell Laboratory 1999-2001 StudMyaStra0r1t Date Dec:00 Sep00 Jun00 Jan00 Mar-99 Apr99 Juk99 `SpermMorphology (N%or9m83al) %8 986 980 977 980 9.1 92 --_ Mean 981 Standard Deviation 09 Minimum 96.1 Maximum 92 E. Bstrous Cycle Parameters and Precoital Interval in Py Females (Table 21, Appendices R-S) Therewere no test substance-related effects on percent days in estrus, diestrus,orproestrus, `mean cycle length, or precoital interval at any dose level. F. Reproductive Indices (Table 22, Appendices T-U) There were no test substance-related effects on mating, fertility, gestation length, number of implantation sites, or implantation efficiency at any dose level. The Py generation fertility index was lower (ot statistically significant) than the control group at 3500 mg/kg/day (75% vs. 90% for the control group). Implantation efficiency was statistically significantly reduced at 3500 mg/kg/day (93% vs. 96.9% for the control group). These changes were considered spurious due to the small magnitude, the unusually high implantation efficiency in the control group, and values were within the historical control range at Haskell Laboratory. These findings were not associated with any test substance-related change in other reproductive parameters in affected ~~ animals (implantations, lttr size, pup viability, estrous cycle or sperm parameters, or reproductiveorgan histopathology). APR Banco, 00a mf ortetn YC A Cite Tw -- 125231: One Generation Reproduction StudyinRats DuPon.5763 ~ Historical Control Data for Haskell Laboratory 1994-2002 StdvFSetbartDate Fertilit1y0n0d0ex(%) Implantatio9n3Ef8ficiency(%) Mar-01 85.0 900 SDeecp-0000 %n02 9961.26 0Jcatn9080 871550 08414 Ma1r1-9957 99030 993042 AJpn9a4 s95i.1 8%673 Mean 868 29 StaMndMaaigrnidimDmueuvmimation 78.25 1000 83454 966 G. Fy Offspring Data 1 Litter Size, Sex Ratio and Pup Survival ~~ (Table 23, Appendix V) There were no test substance-related effects on the number of pups born, bom alive, alive on lay 4,7, 14, or 21, nor were there any effects on sex ratio, or survival indices during the lactation feriod. 2. Pup Weights (Table 24, Appendix W) There was 2 test substance-related effect on pup weights at 3500 mg/kg/day. Mean pup weights vere reduced during the lactation period and were 91%, 86%, 77%, and 76% of the control mean m lactation days 0, 7, 14, and 21, respectively. There was atest substance-related increase in the #onctirdoelncgeroofups)ma(lselewGhroolses bPoadthyoilnogFyy pTaubplsetshaatndweArpepesancdriicfeicsedfoartwweeaannliinngg (r5atsv)s.. 0 pups in the 3. Clinical Observations in Fy Pups (Table 25, Appendix X) fhere were no test substance-related clinical observations at any dose level. _--nm-_ nm a i `Gompany Saritizad. Doss not contain TSCA Cal || 25231:One-Generation Reproduction Study in Rats DuPon.763 ~ H. Fy Rats (Tables -26M-e2a9,n ABpopdeyndWieciegshts-2a)nd Body Weight Gains Therewere test substance-related reductions in body weights and body weight gain in males and females at 3500 mg/kg/day. Consistent with the reduction in pup weight a the end of lactation, 1nean body weights on the day of weaning (test day 1 or postnatal day 21)werealso reduced (76% and 79% of control in males and females, respectively). Weekly mean body weight gains were reduced throughout muchofthe post-weaning period in males (76%-91% of control mean). As a result, weekly mean body weights were consistently reduced throughout the post-weaning period, and mean final body weight (test day 36) and overall weight gan (test days 1-36) were 7% and 89% of the control mean, respectively. Weekly mean body weight gain was reduced for he fist week after weaning in females (86%ofcontrol mean on test days 1-8); however, mean final body weight and overall body weight gain were unaffected. 1 Fy Rats - Food Consumption and Food Efficiency (Tables 30-33, Appendix AA) There were test substance-related reductions in food consumption in males at 3500 mg/kg/day. Mean food consumption was reduced (81%-91%ofthecontrol mean) for the first 3 weeksof the Jost-weaning period in males. As a result, overall food consumption for this period (test days I6) was 919% of the control mean. Mean food efficiency was not affected at any dose level. ~~ 1 Fy Rats - Clinical Observations and Mortality (Tables 34-35, Appendix BB) "here was no test substance-related mortality nor were there any clinical signs of toxicity in any goup. One femalein the 3500 mg/kg/day group was found dead on test day 7 (postnatal y 27); on the day prior to death this animal was weak and hunched over. One male in the 500 mg/kg/day group was also weak and hunched over on test day 6. The mortaliy and clinical igns were considered spurious duteo the low incidence. Fy Rats - Developmental Landmarks (Table 36, Appendix BB) `here were no test substance-related effects on developmental landmarks. The mean age of feputial separation (45.333 days for the 3500 mg/kg/day group vs. 42.778 days for the control {oup) and vaginal opening (33.786 daysforthe 3500 mg/kg/day group vs. 31.772 days for the entrol group) were increased in the 3500 mg/kg/day groups. These changes were not considered ybedue to the test substance butratheran indirect effect of the reduced body weights and body ight gain during the post weaning period. J Reproductive In-Life Toxicology Conclusions ~ 9 fp NOEL for reproductive weights during lactation taotxi3c5i0ty0 imngt/hkigs/sdtauyd.y was 500 mg/kg/day, based on reductions in Fy ~ a -- Company Saniized. Dossnot contain TSCA CBI 125231: One-Generation Reproduction Study in Rats ~~ CLINICAL PATHOLOGY EVALUATIONS DuPonc763 A. Hematology (Tables 37-38, Appendix CC) There were no adverse changes in hematology parameters in rats dosed with the test substance. All statistically significant changes in hematology parameters were considered unrelated to treatment and/or non-adverse (not toxicologically significant). These changes are detailed below. + Red cell mass parameters (red cell count, hemoglobin, hematocrit) were minimally decreased in males dosed with 75, 500, or 3500 mg/kg/day (variable statistical significance). There was a lack of a dose-response relationship in red cell mass effects despite the nearly S0-fold difference in dose between the low and high dose, and the presenceofaclear doserelationship in other parameters indicating exposure to the compound (plasma and urine fluoride). However, the changes at 500 and 3500 mg/kg/day were considered to be probably relatedto treatment because there was a minimal increase in red cell morphologic changes (anisoeytosis, microcytosis, and hypochromasia) in males dosed with 500 or 3500 mg/kg/day, and mildly increased red cell distribution width at 3500 mg/kg/day, indicating a possible dose-related effect. The magnitudeof change in ll red cell parameters was small, and therefore, was considered to be non-adverse --~ + White cell counts were minimally increased in females dosed with 75, 500, or 3500 mg/kg/day (statistically significant only at 3500 mg/kg/day). Increased white cell counts were the result of statistically increased lymphocytes (females dosed with 75 or 3500 mg/kg/day only) and eosinophils (females dosed with 3500 mg/kg/day only). There was a lackof a dose-response relationship in white cell effects despite the nearly 50-fold difference in dose between the low and high dose. There were no other clinical patholoogry histologic changes (e.g. inflammation) that correlated with these minimal changes. In addition, for those mean leukocyte counts (total and individual cell types) that were statistically significant, individual counts were generally within orjust outside the reference. range for individual control rats." Therefore, these changes were consideredunlikelyto be related to treatment and non-adverse. ~~ The'A2L.Y5M7.35.8p3e-r1ce0n4t1i;lAe EcoOunSts0o.r06fe.m0al2e)r"ats aged 19 weeks, reported a lsh are WBC 492-1325: ' --e `Company Sanitized. Doss not contain TSCA CBI 25231: OneGeneration Reproduction Study in Rats DuPont9763 -- B. Clinical Chemistry (Tables 3940, Appendix CC) There were no adverse changes in serum clinical parameters in rats dosed with the test substance. Statistically significant changes in serum clinical chemistry parameters were considered unrelated to treatment and/or non-adverse (not toxicologically significant). These changes are. detailed below. + Alanine aminotransferase activity wasminimally increased in malesdosedwith 75, 500 (not statistically significant), or 3500 mg/kg/day. There was a lackof a dose-response relationship in this effect despite the nearly S0-fold difference in dose between the low and high dose, and the presence of a clear dose-relationship in other parameters indicating exposure to the: compound (plasma and urine fluoride, hepatocellular hypertrophy). Tn addition, the control `mean is near the low end of the laboratory historical range for mean alanine aminotransferase: activity in males of approximately the same age." Therefore, although it is possible that the. changes in alanine aminotransferase activity are related to treatment, it is more likely that the apparent increased activity in the treated group was duetto he unusually low mean activity in the control group. C. Plasma and Urine Fluoride (Tables 39and 41, Appendix CC) ~ Plasma and urine fluoride were measured in males only. Plasma fluoride was increased in males dosed with S00 or 3500 mg/kg/day, while urine fluoride was increased in malesdosedwith 75 (not statistically significant), 500, or 3500 mg/kg/day (Clinical Pathology Text Table 1). These changes occurred in adose-related manner. Increases in plasma and urine fluoride indicate: exposure and metabolism of a luoride-containing molecule. or7 Clinical Pathology Text Table 1: Mean urine and plasma fluoride for males [[o = TT 0[ sw] [%ofconwolmeasn | NA | 445% | 1as5% | a235% | 7 Statistical significance is indicated by bold italicized type. ~ Mesmnalseasl(an3i0n.e65amwieneoktrsaonlsdf)erisas3e0-a6ct5ivUitLy for younger males (12-14weeksold) is 28-50 UAL, wile that for oder i. -- Ea -- `Company Sanitized. Doss not contain TSCA CBI 125231: OneGenertion Reproduction Stady in Rts DuPont9763 D. Clinical Pathology Conclusions There were no adverse changes in clinical pathology parameters. Therefore, under the conditions of this study and for the clinical pathology parameters measured, the no-adverse-cffect level was 3500 mg/kg/day for males and females, the highest dose administered, based on the lack of adverse findings at ths dose. Treatment related but non-adverse changes included minimally decreased red cell mass pmaorrapmheotlerosg,yiinncmraealseesddroesdecdelwlidtihst5r0i0buotiro3n5w0i0dtmhg/(k3g5/0d0aym.g/Ikng/adddaiytioonnl,y)i,ncarnedasiendcrpelaassemdareadndcell urine 3500 fluoride measurements were observed me/kg/day; the presence of fluoride in in males dosed with 75 (urine fluoride only), plasma and urine indicates exposure to and 500, or `metabolismof fluoride-containing molecule. --~ --~ wo -- `Company Sanitized. Does not contain TSCA CBI ~ ANATOMICAL PATHOLOGY A. Mortality (Py Adult Rats - Appendices K, L-N, and FF) Somme el (Fy AdultRats -- Appendices BB and GG) B. Organ Weight Data (Py Adult Rats - Tables 42-43, Appendix DD) (Fy Adult Rats -- Tables 44-45, Appendix EE) I There were statistically significant test substance-related higher mean liver and kidney weights in `male and female P) rats as listed in the following table: [Dos |e 75mgG /kgdr ay | o5u 00mgp /kg/d: ay | 3500 mg/kg/d: [Oman |Male[Female|Male [Female|Male|Female | ~ pmppf[w[ | rrsoeemmmms[||S = = TTT====[T ||R T=T T= == T == |R ETTTTTTTTT]]]] Liver(erle:lativeto brbrain) 7 T Higher liver weights in Py rats correlated with microscopic hepatocellular hypertrophy and was considered non-adverse (see discussion in Microscopic Findings). There was no microscopic correlate for higher kidney weight. Higher kidney weight was most likely due to hypertrophy, which was below the thresholdofmicroscopic detection, and was considered non-adverse. Other statistically significant organ weight changes (lowerabsolute,relative to brain and/or higher relative to body) in the epididymides, seminal vesicles, prostate and/or brain in Py males from the high dose group were interpreted to be the result of lower final body weight in that group and not test substance-related. The mean relative (to body) liver weight was significantly higher than the control in the high dose female F; adults, and was considered a test substance-related effect. There was no icroscopic correlate and the small weight increase was most likely due to hepatocellular hypertrophy that was below the threshold of microscopic detection. This weight change was ~ `onsidered a non-adverse finding (See discussion of hepatocellular hypertrophy in Microscopic rr findings section). Cr---------- H:25231: One-Generstion Reproduction Study in Rats DuPon9763 --~ There were noothertestsubstance-relatedorgan weight effects in Fi adult rats. Other significant organ weight changes (lower absolute, relative to brain and/or higher relative to body) in the testes, epididymides, and/or prostate in Fy males from the high dose group were interpreotbede the result of lowerfinal body weight in that group and not test substance related. Prostate weight irom one high dose male rat (Animal No. 660638) was removed from the weight calculations due 10a weighing error. C. Gross Findings (1 Adult Rats ~Tables 46-47, Appendix FF) (Fy Adult Rats -- Tables 48-49, Appendix GG) (Weanlings -- Table 50-51, Appendix HH and I) (Pups - Tables 52-53, Appendix Il There were no test substance-related gross observations in adult Py, Fy, or in weanling rats. Gross observations occurred in low incidences and were randomly distributed across control and treatment groups. Observations in pups of "lungs not expanded," and "no milk spot in the stomach," are ronspecific lesions that are commonly seen in ell pups that are bom dead, and thus are not considered to be compound-related. Pup viability and mortality are discussed elsewhere in this --~ port. 0. Microscopic Findings (Py Adult Rats ~ Tables 54-55; Appendix FF) (Fy Adult Rats -- Tables 56-57, Appendix GG) (Weanling Female Rats Table 58, Appendix HE) 1. Py Adult Rats (Py Adult Ra~Ttablses 54-55; Appendix FF) Hepatocellular hypertrophy in the liver and chronic progressive nephropathy in the kidney were increased in incidence in Py males from the 500 and 3500 mg/kg/daydose groups, and were terpreted to be test substance-related. Hepatocellular hypertrophy depicted hepatocytes with `alarged eosinophilic cytoplasm with intact hepatic cords and was interpreted to be an adaptive hysiological response to exposure to a xenobiotic, and not biologically adverse. Chronic Fogressive nephropathy depicted basophilic stainingof tubular epithelium, often with enlarged. clei, sometimes accompanied by a minimal inflammatory component and minimal peritubular sromal thickening. Chronic progressive nephropathy occurs commonly as a spontaneous lesion rats and the increased incidences noted in the current study represent a compound-related rl onset ofa typical age-related finding. The severity of this lesion was minimal in treated nd in control animals and was unaccompanied by any correlative adverse clinical pathology ndings (see Clinical Pathology portion of this report. Kidney changes in Py males administered 0 mg/kg/day and above were considered adverse findings. hyroid follicular hypertrophy was increased in incidence in all dose groups of Py males --~ 5 mg/kg/day and higher) and in females in the intermediate and high (500 and 3500 mg/kg/day) EC `Company Sanitized. Does not contain TSCA cay 25231: OneGeneration Reproduction Study in Rats DuPont5763 ~~ d2omsaelgersou(posn.e 5H0y0pemrgt/rkogp/hdyaywaasndgeonneera3l5ly00mimngi/mkag/ldiany)s.eveFroiltlyicwuiltahr mhoydpeerrtartoepsheyvweraistydidaigangonosseedd in when the follicular epithelium was tall columnar with a finely granular cytoplasm. Thyroid hypertrophy was considered testsubstancerelated and potentially adverse. "Thyroid follicles containing altered colloid were found in thyroids from controls as well as weated animals. An increase in incidence and/or an increase in the number of affected follicles, and thus grade, was interpreted to be treatment-related. Altered colloid described as clumped or granular has been reported to occur spontaneousilyn Sprague-Dawley rats with increasing, iinnctihdeeSnpcerawgiuteh-iDnacwrleaesyinragt.agIen.t?h"e Tphruesse,natlstteurdatyi,otnsheirne cwoalslooidnlayreatkrneoawtmnetnot roeclcautredspionnctraenaesoeuisnly grade and not in incidence of the observation for Py males at all dose levels. There was an increase in the incidence of altered colloid in the 500 and 3500 mg/kg/day group Py females. There was no consistent association between the presence or absence of altered colloid with follicles that were lined by hypertrophic or non-hypertzophic follicular cells. Because altered colloid occurs spontaneously in healthy Sprague-Dawley rat, and because increases in is grading score did not correlate with degenerative morphologic observations, shered colloid was interpreted in the present study as not biological meaningful and not adverse. 2. Fy AdultRats (Fy Adult Rats ~ Tables 56-57, Appendix GG) ~ Minimal hypertrophy of thyroid follicular epithelium was increased in incidence in Fi adult sales at all test substance dose groups and in one Fy adult female from the 3500 mg/kg/day dose soup. Altered colloid was detected in very few animals across dose groups nd was not ansidered to be test substance-related in the Fy adults. Thyroid hypertrophy was considered test abstance-related and potentially adverse. The character and severity of thyroid hypertrophy was `teirgyhesriimniltahrebFeytgweeneenraatfifoenctceodmPpyaarneddFtyo atnhiemPaylsg.enIenrafteimoanl.es, the NOEL for thyroid changes was 3. Fy Weanlings (Weanling FemaleRats Table 58, AppendixHH) here were no test substance-related findings in the weanlings examined. The few lesions esent (hydronephrosis, bone fracture, urinary bladder inflammation with mucosal hyperplasia) fe commonly observed spontaneous or incidental lesions in this age and strainofrat 4 Anatomic Pathology Conclusions heno-observed-adverse-effect level (NOEL) for this study isdefinedas the highest dose at hich toxicologically important effects attributable to the test substance were not detected. {tnhdoelrotghye cwoansdintoitondsetoefrtmhiinsesdtuidnyP,ybaansdedFyonadhuylptemratlreosp,hywaofst7h5yrmogi/dkegp/idthaeylifourm,PythaeduNlOt EfeLmafloers, $d was 500 mg/kg/day for Fy adult females. --_ "Company Sanitized. Does not contain TSCA CBI H25231: OneGeneration Reproduction Sty in Rats DuPont9763 CONCLUSIONS aUnnddeFr trhaet,cobnadsietdioonnstohfytrhoiisdsftouldlyi,cualanroh-oybpseerrtvreodp-heyffinecPtylaenvedlF(NaOduElLt)mawlaessnaott>7de5tmegr/mkign/eddayfo.r Py wTehieghNtOsEthLrofuorgrheopurtotdhuecetnitviereeffleaccttastiwoanspe5r0i0odmgf/okrgF/ydalyt,rbsasaetd3o5n00remdgu/cktgi/odnasy.in mean pup --~ --_ * tThheeteNstOsuEbsftLoanctheiswesrtuednyotiddeteefcnteedd.a Tthhues,hfioghehstisdotsdesa.ttwhheNicOh EtxLicoilsocgqiuciavllleynitmptoortthaentNfOeEcLtsasadteifbiunetdblbey to the United SatesEnvironmental Protesion Agency * an to th no-observed-adverse-efec level (NOAEL) as: defined by the European Union | TT | Company Sanitized. Doss not contain TSCA CBI | H:25231;OneGeneration Reproduction dyinRats DuPont. 763 = REFERENCES 1. DuPont Haskell Laboratory, Repeated Dose Oral Toxicity, Gavage Range-Finding Stud, 2. DuPont Haskell Laboratory, Repeated Dose Oral Toxicity, Gavage Range-Finding Studs Rats. Unpublished Report. 3. DuPont Haskell Laboggtory (2002). Subchronic Toxicity, 90-Day Oral Gavage Study in Rats. `Unpublished Report 4. Draper, NR. and Smith, H. (1981). Applied Regression Analysis, 2 edition, pp 266-273. `Wiley, New York. 5. Selwyn, MR. (1995). anima safety studies. JTohuernuasleoofftthreenAdmetersitcsatno dCeotlelremgieonefaTnoox-iocbosleorgvyab1l4e(-2e)f,f1e5ct8-l1e6v5el. in 6. Jonckheere, AR. (1954). Adistribution-free K-sample test against ordered altematives. `Biometrika 41, 133-145. 7. LSteavteinstei,csH(..(1O9l6k0i)n., eRdo)b,upstp t2e7s8t-f2o9r2e.quSatlaintyfoorfdvUanriivanecressi.tyCPornestsr,ibPuatlioonAslttoo.Probability and 8. Shapiro, 5.5. and Wilk., M.B. (1965). An analysis of variance test for normality (complete samples). Biometrika 52, 591-611 --_~ 9. S34n9e.d3e5c2o.r,TGh.eW.loawnadSCtoactherUanni,veWr.sGit.y(P1r9e6s7s),.AmSteast.istical Methods, 6 edition, pp 246-248 and 10. Dunnett, C:W. with acontrol. (1955). A multiple comparison procedure J. Amer. Statist. Assoc. 50, 1096-1121 for comparing several treatments 11. Kruskal, W.H. and Wallis, W.A. (1952). Use of ranks in one-criterion analysis of variance. J. Amer. Statist. Assoc. 47, 583-621. 12. Dunn, O.J. (1964). Multiple contrasts using rank sums. Technometris 6, 241-252. 13. Dcoemmppusttaetri,onAaPl,asSpeelctwsyno,fMmiRx.e,dPmaotedle,lC:anMa.l,ysainsd. RTohteh,JoAuJr.na(l1o9f84t)h.e SRtoaytiasltiSctaaltiasntdical Society, Series C (Applied Statistics) 33(2), 203-214. 14. MEixlpleirkiemne,ntGs..A.LiafnedtJiomhenLseoanr,nDi.nAg.Pu(b1l9i8c4a)t.ioAnnsa,lByeslimsoonftM.essy Data, Volume 1.: Designed 15. HLisnue,a1r.CM.od(e1l9.92)J.ourTnhaeloFfacCtoormpAuntaaltytiiocnaAlpparnodaGcrhaptohiSciamlulSttaatniestoiucss I1,nf1e5r1e-n1c6e8i.n"the General 16. FNieshwerY,oRr.kA.. (1985). Statistical Methods for Research Workers, 13" edition. Haffner, 17. Haseman, JK. and Hogan, M.D. (1975). Selection of the experimental unit in teratology studies. Teratology, 12, 165-171 -- 18. Patefield, W. (1982). Exact test for trends in ordered contingency tables. Applied Statistics 31,3243 -- EE `Company Sanitized. Dossnotcontain TSCA CBI #25231,OneGeneon Regroduction Stay in Rats Dupont9763 ~ 19. DuPont Pharmaceuticals Company. (April 3, 2000). Clinical Pathology Reference Ranges `The 2.5-97.5 percentile counts for female rats aged 19 weeks, reported as cells/uL, are WBC 4.92-13.25; ALYM 3.83-10.41; AEOS 0.06-0.22). 20. DuPont Haskell Laboratory. Clinical Pathology Reference Ranges. The Haskell historical range of means for younger males (12-14 weeks old) is 28-50 U/L, while that for older males (30-65 weeks old) is 30-65 U/L. 21. Rao-Rupanagudi, S., Heywood, R., and Gopinath, C. (1992). Age-related Changes in Thyroid Structures and Function in Sprague-Dawley Rats. Vet. Pathol., Vol. 29, No. 4, pp. 278-287. 22. Hazard Evaluation Division, Standard Evaluation Procedure, Toxicity Potential: Guidance for Analysis and Evaluationof Subchronic and Chronic Exposure Studies Paynter, O. E. et al., United States Environmental Protection Agency, Officeof Pesticide Programs, `Washington, D.C., 20406. EPA-540/9-85-020. (June 1985). 23. Risk Assessment of Notified New Substances. Technical Guidance Document (X1/283/94-EN), Chapter I, Sections 2.24 and 2.25. 1994. --~ -- -- = Company Saniized. Does not contain TSCA CBI F-25231: One.Generation Reproduction Study inRats -- DuPont9763 TABLES --~ ~~ mmr `Company Sanitized. Does not contain TSCA CBI H25231: OneGeneration Reproduction Sudy in Rats --_ TABLES EXPLANATORY NOTES Notes TeTsesttDDaayyss 7167950 = = PCroehmaabtiitantgipoenrpieordiod Abbreviations - Clinical Pathology `SRBCuof- mHreemdmabtollaogcoyerVlalocloyuudenst HGB - hemoglobin HCT MCV -- meheamnatcoocrrpituscular volume MCH MCHC - mean mean corpuscular corpuscular hemoglobin hemoglobin concentration RDW - redcel distribution width ARET - absolutereticulocyecount PLT - platelet count WBC - whiteblcoellocoudnt ~~ AALNYEMU -- abasbosolluutteenleyumtprhopohciylteallforms) AMON - absolutemonocyte AEOS absoluteeosinophil AALBUASC - aabsoblutselbaarsogopeuhlnisltuaintedceell Summary of Serum and Plasma Chemistry Values AST - aspartateaminotransferase: SADLHT -- saolrabniitnole daemihnyodtrroagnesfnearsaese PLU - plasmafluoride SumUmFaLrUy o-f UurriinnaelfylsuiosriVdael.ues : DuPont9763 --_ --_--eeeee Company Sanitized. Doss nt contain TSCA CBI --~ ~ . --~ H25231: OneGeneration Reproducion Study in Rts Dupont763 TABLE 1 SUMMARY OF DOSING SOLUTION ANALYSES Semple Type ConcentraandsStoabnilisty ofF-25231 (my TestDay 2 Nominal Concentration Verification 1s wb o 100 es 700 18218 001762) aon Pl Average Measured Conc @s3) 12) 108 94.4 054) 1 Average Percent Nominal Standard Deviation a0 29 [2 240 85) 23 Coefficientof Variation 7% as 5% S0t-uDbaiylRyoom Temperature! 108 944 01 S-hourRoom Temperatures. 0 108 4747) 078599) @0 @n [0 Test Day 9 `ConcentrationVerification nb ah --b 1568 wh at (1040) AAvveerraaggee PMeeracseunrteNdomCionnaet.e 014472) Standard Deviation CoefficientofVariation 20 14% `0S-uDbaiyltRyoom Temperature! 142 S-hour Room Temperatures 14615) hb --b 100) CTonecsetnDtarayt4io6n Verification 159 13 060 TestDay 114 1706,0) a1B14o ao5n . 080) ny amy = DoRsiInSgEsoiustipenon i. 25751/mLbag on 5mldoevolume. b & MMNeeuamnberrresesitntpffooarraeulrpbaellssyssesieesosnhaetlehyepsecgofiotvaeelspouerrimcgpennatlof ppolr.al vcs. & MMSiaeamanpni,eSesDs(.TteasftnoDdTaCyoVt.29Df)aorthdeu7lpdliaccoartoneocsmnarmeaptmloepnsrcavaeurcriufelificaoetrdio3n0hsovauemrrpsi.lfeysnuisfeodrfmoitbysoeflmiinxetufroresilty spc. RI SDaumppllcesssnostamspolbemsistuebdmrite1d0.0 mMge/amleanadl70ep0ormiegdr. . lees. r5n `Company Sanitized. Doesnotcontain TSCA CBI ~~ g i : & o | si a:8:838:8:2:.a.a22.383.38 |@ ]3 g "7 gagdgnpdgigegegedn eg : ] i fiii22iiatza ia iA zc g f& ] BR GRniadaandd - i: Si3isis:sisogz Pf fe. 8% 25 8% 35 8% 82 23 82 83 3521 g Eo ETRY RTSYIVT ENTS +3 3 4 :2 iu p ssErsa zp32fs 3aayz2sfE2aea3gaza2naan3ngagzE2iegnad3 yl.i}1f2 7 grgagngngsgRgagegRg BY 235 i 3 ;: ~3 FH] ;8g2g : : iid 1i 83: 7 RRR202BE 2 E83 E 5 Z 3 R (3 2% FiE & ws ~ i g i ? dddddd po 58 ggugdgegigy | 2 Coo 1 1o 838 FSeoasmsgsEsgassEoeeRcss 2 I ~ 32 ii iid. - g 2 grfe dgefggegggeEgEagieagis oo ol :ii:geit 3 gs, $8 3% go gu gage HE i i5 i#Ei3 S . LER ~g ; 8 i 5% 49 3d 4 48 ud gs vac ad wd BE i g Is : 2 2 2 2 2 2 = 2-2 0 5 i 5 % go 35 go 5 8 Sg dd 84 3 te 5 =i 2 a mR a a Raz 2 = i &5 8i"o 2723439 g3r53g8a3s3 a83t a8e3 a5e% e41e8 8=v3) ifia3g 2{ Zi g3is i5 8j8it-2tr5 E8 R5a3 cs8s5 |n8a3 Hg 2 El. ~:} # g graTaTaTata gsgy 3 fg Hullsaan i _ LI FP . 3 Efe REARING , 3:23:33 7%%o:Fs 3 EERE EREREE CF LI 1 : BTEeL, i Herrera aly g FEF RE R85 7 CERT 8: 5i EN 3 54 ~ il. ~g o g g dgdgd3d3d8a8d8d3d88ady |} ii3 iHEBREN T RR E gik ER gEeEgRsEgd gvEgnEgd i ] : szzsssgsasy J 3 3s as g4 Ee 24 34 3% 84 g3 8 84 58 2 FL iiiiidiiiidi gi If 84 25 gn s $5 gd gd 53 g4 = Ei: j 5 EATER g] : : E.0 511453 Ho sasssssal |] i i ~ 8i ! i s 58 Fi. z $ -i::::::::3 i fg iiiiigiiiidei Z i a. UE --~ 5 888g zgs sg 8 . 251, ARgEifERnIgREsRLE aR ag Af " f iiiiiiiiiag:l 2I Ei7 ApEE3RoIsSGReInNgGrInIsIoNeCgREIsNnGaRtAz=Ma gg5:balof 13 LL } firtrssae aes trad ~3 5 &] & jm [adie a 0g 35 : 3 i g 2 oa aoa B : z3 = 2 203 a co ! RU AT AR INE SE7 ngd5 i8dg85da3 s iz{ 2 A2 ~ | BE. fais : . Ef err| i ooo] 3 8 8 58 3 : C35I] Bi E g is i: Li --~F FH ~8 :3 8 i. 3333 82 as 9 2% 3od 3 z s 2 8 5% gg gu) i i ii: 4 8 Pp 5Th3, 8202837888% 8gdg 2 3 Efe 23 egUd i $gs8:, i 34 |5 i: : 8Rid i } : i i 2 a I ERERRE Ze, sigrazzi I Bg iui i i1z1 Agise ~i li ~~g sy 8.3.32 gu HERES i g oo. 3 E Ap Ea E| ]: 3 ok 1 25, i 5% EEE g i: ~ g|3 z 5 3 2 i : isiiiiiisedi i : TTS go gS 7 87 87 9 87 80 80 89 f es 2 om mm mam mo ~ id $8888 8553:35 3 [ 2 987 87 8 87 87 a0 27 87 20 29 ty 5 iii: 3:33: 3 4%sk 3: 83Zui . 5i7:t383%y |. EL fi 21 E2lisaisagioi5li5 [i3 ;BF git addroe znfs gd i : iis & =a ~g : j 2 : 3iiiisizaig 2 f 2 "SS 86 69 oo oo oo So oo oo oo oo i P iigsiiiiirig : g FEE] 1: | 3 Me siargagaoziil 8 g git TREE EEE ET ad ~ = s 3% ad +a ~ gf i. siiiiiiiiidi |i EF ARH RANININA Tg 2 ao] i & ssg3s88s8s8 8g fb 3 PN 5oa A8 Siiissaaaazsd RrATEmETATETATETE " 3 t3eS PE BARA ; COR aa . I a :: & mm mm ~~~ MN SDETISEEREEEIIIGIII E a eo B58 A$s 3a 8m5m3m38m8m8m ~ s ~sgA Ho 0S NE CN AB VY m3 af ME 93 99 GIEIITEIEIEIGEGININIEY P:s olig5 8 5i 3| i 28 i 2 gg gz;ssfsgsgi 5 gi i2 Egs yBless ryygoF R pP o EP s 3 gi" ca RRs 28 on oz AEA 2 FE {ie ~~ F EE . ~ z g z i o Hg 8% 73 8% 88 2 3E is:i i SmEnEe | i zkEe TcEo eazgd : z BURT RN T 1 I $5 au i;s2 - 2 ~ 3g g S| Zz J 5 : g : gE 3IiERE = i : 5s 533 3s 333sgEgE & 5 58 22233335 x 1 ~ E w 2I 33fEEasneEy - ) Th EEES 2 2 = = a 23 Bo 8% 02 om aol i |! i sz ix 1 in 7 : rEH rra|iUyE J gi CC Eg 44 pi ~g ; BF 5 3 z j i 5 .| 125231 OnGeeneration Reproduction Sd n Rats. ~ TABLE 16 Duronsrs SUMMARY OF CLINICAL OBSERVATIONS IN P; MALE RATS Number of Rats wich Observation woe GaneGsoapnV:: on100 q3om5n.o vSW oe Rvsiuoo oaseruaTIOns ADDllLosepemenacaiittaoee Rpeenmiisration os; `os `s5 `ii LLSRaaaenitenaeodtosuch o0o :03 oo0 :3Ff 000i SStaaiinneedd NFoesrstneun o: 00 o: 5i Statistically stamificant Trend by Cochran-Amitage trend tests p < 0.05. ~ -- EE Company Sanlizad.Doos not containTSCACBI 25231: One-Generation Reproduction Study in Rats Dupont9763 --~ TABLE 17 SUMMARY OF CLINICAL OBSERAVNADTICOONHSABIINTPyATFIEOMNALE RATS DURING PREMATING Nunber of Rats with Observation DOSE (mg/kgG/RdOaUyP):: II0-0 I7V5-0 5VI0-00 V3I5I0I0-0 N20 20 20 20 OBSERVATIONS Alhoupncehceida Over 3 20 1o 21 SaStlaviantediopnerineun oo 0 0o 138 Statistically significant trend by Cochran-Armitage trend test; p < 0.05. --~ -- a -- -- Company Sanitized. Dossnotcontain TSCA CBI 25231: OneGenerationReproduction StudyinRats DuPoni-9763 --~ TABLE18 SUMMARY OF CLINICAL OBSERVATIONS IN P; FEMALE RATS DURING GESTATION Number of Rats with Observation DOSE (mg/kgG/RdOaUyP):: 11-0 N20 I7v5-0 V5I00D V3I5I0I0-0 I) 17 18 OBSERVATIONS ASloorpeecTiaail 5o o1 6 12 Notec:opuTlhaitsiontaobblseerivnecdl.udes clinical observations from animals with evidence of There were no statistically significant trends by Cochran-Armitage trend test; p< 0.05. --~ ~~ _-- 7 Company Santtized. Dossnotcontain TSCA CBI H25231: One-Generaion Reproduction Study in Rats DuPont9763 --_~ TABLE 19 SUMMARY OF CLINICAL OBSERVATIONS IN P; FEMALE RATS DURING LACTATION GRovp: fN1u-m0ber of WR-a0ts_witVhIGOiven SVIiIgIn-0 D0SE (mg/kg/day):Nos0 1795 15900 351050 OBSERVATIONS ATlootapleciNoa. of Rats with Masses 50 ao 5 31 Site: 1 Mass Chest (2.0 cm) 0 o 1 Therpe<we0r.0e5.no statistically significant trends by Cochran-Armitage trend test; --~ -- -- = `CompanSy SAanitized. Doss not contain TS--CA CBI H25231: OneGeneration Reproduction StudyinRats DuPont9763 --~ TABLE 20 SUMMARY OF SPERM PARAMETERSINP; MALE RATS Dose (mg/kGgr/oduapys): 1- 0 71s-0 v5-000 v3i510-00 worTPLeIrcTeYnt Motile 93.368 93.059 Standard Deviation 3.890 (19)a 2.331 (17) 92.389 7.594 (18) 92.588 4.124 (17) MORP`HPeOrLcOeGnYt,. Normal Standard Deviation 09.698.505(319) 0.69396.10(519) 98.3168 1.030 (19) 98.2948 1.251 (27) EPIPDeIrDYCMaAuLdaSPERM (4illions) 305.558 Standard Deviation 27.539 (19) 70.229813.26(520) 69.258172.71(619) 462.48668.95(618) oStrandgarradn CDaeuvdiaation 11302.529351 5(319) 311039.87.425(520) 3381.1487.214(719) 2061.1065.329(418) TESPTeIrCULTeAsRtiSsPERMATIDS (Milli1o7n4s).405 167.720 Standard Deviation 19.819 (19) 42.023 (20) 25.117203.51(119) 22.106393.57(818) --~ PSetrandgarradn TDeesvtiaitsion 1192.128.475(319) 271.1215.075(520) 14.151264.62(619) 17.131387.0980) a Number in grow is in parentheses. statistically significant trend by Jonckheere-Terpstra test; p < 0.05. -- EK] Comp-- anySanitized. DossnotcontainTSCACBI H-25231:One-Generation ReproductionStudyinRats DuPon9763 --_ TABLE21 MEAN ESTROUS CYCLE PARAMETERS AND PRECOITAL INTERVAL INP; FEMALE RATS oPfercDeanyts PofercDeanyts PofercDeanyts lean Cycle Group (maD/oksge/.day) N Sistnrus Diiesntrus Proienstrus Le(ndagytsh) 1-0 20 2 6 1 430.52 w-0 75 20 2 6 u 1.20.3) vi-o s0 20 22 6 13 2.20.3) vio 3500 20 35 6a 10 ab wStealn.dard deviation is presented in parentheses. e503) TherDerewceorietanlo isnttaetrivsatlicbayllJyoncsikghneiefrisc-aTnetrpsttrernadsteisnt e(sptr<ou0s.0c5y).cle Pryeecoaintal To(tcearysv)al 2.90. 320.80 3.20.00 3.0(3.6) length or -- Eu `Company Sanitized. Does not contaiinnTSCACBI H25231: OneGenerationReproduction StudyinRats DuPont9763 --~ TABLE 22 SUMMARY OF REPRODUCTIVE INDICES: P; GENERATION DOMSEATE(RmNgA/LkgG/RdOaUyP):: MATI(NNoG. TcNoDpEuXla(t3e)d/cohoused) FERT(NIoL.ITpYreIgNnDaEnXt/(c8o)pulated) GEST(ANToI.ONinLEgNrGoTuHp) (days) 110-0 (1200/020) (185/020) 2a2e3 I7Vs-0 (1995/20) (1190/019) a2n.5a V5I00O (189/520) (119/0109) a22n.a2 V3I5I0I0-0 (210/0200) (157/520) a22m3a NUMBpEeRr OpFreIgMnPaLnAtNTfAeTmIaOlNe SITES Standard Deviation (No. in group) 3.1039.(318) 4.318(s19) 2.1133(.139) 1.8133(915) THPL`ASNtaTnAdTaIrOdNpEeFvFiIaCtIiEoNnC(YNo.(3)iDn group) _ 5.196.(918) 6.6947(.109) 8.3943(.169) 6.8639.00105) a Gfeosrtwahtiicohn nloenegvtihdecnocueldofnotcobpeulcaatlicounlawtasedobfsoerrv2edf.emales that were pregnant b Number of pups born/number of implantation sites X 100. ~ Theriendwiecrees bnoy sCotcahtriasnt-iAcramliltyagseignteisfti;canpt<t0r.e0n5d.s in mating or fertility Ther`geeswtearteionnolesntgatthistoircnaullmybersiogfnifiimcpalnatntadtiifofneresnicteess bfyroJmonccoknhtireoelrei-nTerpstra test;p < 0.05. Steaftfiisciteinccayllbyy Jsoingcnkihfeiecraent-Tedripfsfterraencteestf:ropm <co0n.t0r5o.l in implantation --~ 7 Company Sanitizod, Doesnotcontain TSCACBI H25231: One-Generaion ReproductionStudyinRats DuPont9763 ~~ TABLE 23 MEAN PUP NUMBERS AND SURVIVAL: F; GENERATION Dom se (n na/kaGldRaUyP):: 1 -0-70s wo 18 is V0IO 19 V3I50O0 15 Born Mw e om OF Pe ups/mLn IsTTER me 24 Bo Born Alive Dey Day 4 4 preculling Poscculling w12e7 mnaa 2ow3s uasa 7.8 73 8.0 7.9 Day 7 Dey 14 7.8 7.3 8.0 75 7.8 7 8.0 7.9 Day 21 8 7.3 8.0 7.9 sBoornn Alive ERY sen op WLR puPoSs/LITEER 6.6 6.2 0 67 pr 52 sis DDaayy 44 Psroesctuelullilnigng ewro 63s 5352 sals s Day 7 bey 16 wo ao 3.9 3.9 3.5 39 39 as ~ Day 21 wo 5 3.9 3 Mea ABER oF FEMALE Pups/uirEER Born Born Alive 6611 ssooaa 6eaa 76.0 bDeayy 44 Prroesctuelulliinngg ssoe sseeaa eaaa 6a1s Day 7 Day 14 se as se ae aa aa a0 a0 Day 21 38 se an a0 Sex Ratio (males) suRvIvaL (8) 05 oss 050 ous GMeesatnatioBnornInAdleixvde 1909010 19090.70 1s0e0.s0 1s0e0.d0 L0a-c4tDaatyiovniaTbnidleixtty sis se ss ses 100.0 100.0 100.0 93.2 Litter survivaid mmm emirR J00 R100.0ere 200.m0 sH 100.e 0 5 & MTeaerarcnceennpsterclleiinttttteerrsssurvdbioevrlanilvweirfterhdomhaDatavyiLnega4staFtoosntleeeuapslutlpinoagnleitovleiDvaoenypu2Dp1a..y 21 Therpfeearwceternset n<boo0rsn0tasatliisvte.ica0l-l4ydsaiygnviifaibcialnitty,treonrdslaicntantuimobnerinodfexpubpys,Josnecxkhreaetrieo-,Temrepasntra --~ harTev wCeorcthrnaon-SAteamtiitsatgiecatlelsyt:sipg<nif0i.0c5a.nt trends Statistics ere performed on combined pups per in gestation litcer only. index Male and and litter female survival data are resented for information only: -- 7 CompanySanitizod.DossnotcontTSaCAiC~nB F-25231: OnGeeneration Reproduction Study in Rats DuPont 9763 -- TABLE24 ME PUPA WEIGN HTS: Fi GENERATION DOSMEATE(RmNgA/LkgG/RdOaUyP:): 3 ay 0 Day Proculling Day Postculling Day 7 Day 14 Day 21 IIo-0 18 690.58 mia 1.00.2) mas 36.9 2.2) 58.83.01 v7=5o v5-00o vi3n5i0-0o 1 19 1s MEAN PUP WEIGHTS (grams) 7.10.8) 5.80.6) 530.50 mead awsam laa mead aan 010s moss 102 15.0@5 BES B03 mG S.405.600 5.205.844.6690 MEAN MALE PUP WEIGHTS (grams) Day 0 10.05 7.20.85 630.6 5.50.5) Day 4 Preculling maa neem mean 030.0 Day 4 Posteulling Day 7 ns 1.90.5) mean asam wa 83023 020.8 15.260 Day 14 32a Boab 6103) 2876.5 ~ Day 21 60.4.0) G.0(.MP 56.36.00 45.20.85) MEAN FEMALE PUP WEIGHTS (grams Day 0 6s0.0 6sO.mE 670.6 6.20.5 Day Preculling 10.7 0.) mig usamn 9.91.3) Day Posteulling Day 7 107 0.) 16.9 (1.0) migae maase 1307 mses 0.00.3 8G. Day 14 36.0 (2.1) Mae IIE 2820.9) Day 21 5100.8) sso ame 6.205.600 43.965) ab Sotwaendsard deviation is reported in parentheses a wwoos + Statistically significant trend by linear contrast of least square means; < 0.05 Note:FemaSlteatdiasttaicaarle apnraelsyesnecsedwefroer cionnfdourcmtaetdioonn otnhley.combined pup weights. Male and --~ 3 Company Santiized. Doesnotc--_o--nTtSaCAiCBnI H25231: OneGenerationReproductionStadyinRats DuPont.9763 -- TABLE 25 SUMMARY OF PUP CLINICAL OBSERVATIONS: F; GENERATION DOSMEATE(RmNgA/Lkg/GRdOaUyP):: II0-0 I7V5-0 5V0I-00 V3I5I0I0-0 OBSERVATIONS SDriaslclhaWrhgeoleRigBhotdyRear Leg(s) SoSurbecutaneous Hemorrhage Right Rear Paw Missing o0 o0 o0 11am) oo o oo 11am) o 1m TNOUTMABLERNUOMFBELRITTOEFRSSIGANFSFECTED o0 00 0 2a TOTAL NUMBER OF LITTERS 18 19 19 is Nnuumrbbeerrss oinutpsairdeentthheesepsarearnethetsheesnuamrebertheofnulmibtetrersofafpfuepcsteadf.fected; the Thepre<we0r.e05no statistically significant trends by Cochran-Armitage test; -- is - & Company Sanitized.Dossntcontain TSCA CBI ~ 2 8 H2 33 5% 8% 38 32 28 3 * g9 fd dd gd gu 38 2 = 2 23 a5 a8 88 $5 2 g 5 Cea ao 5 - 85; 2 RR h: i 8 iii: i 2} i: i ii ~1 Je ~ g| :]5 i : ; % 4d 6s d 2% o- gd g zfp e2si2n3ai3a.2eg3 3 :3 = $ 3 8 8 ZX v 2 ~ | g5g5.sn2 e3a3 2 n2g 3 y|* 2 Bg 3% 37 g% @ g gy i :| gZ "la.ia3t3 8. 5 C5. . a ~~ g, % 8 2 ao af aiaiad 22 HPTZ 394% g2d2 gadg g8d8 g$e3 g3e8 3 3 23 23 EFA EEE 3 .: B8 i z FB, 2 rr if 3 fhe IITRREEARGY fa i iE. : vy is8 i jgm ocr oR Riya 8 Hi ~3 i ; qo - 3 gr ELICEI AE LIE i EEE EE i | fi muEzann i a z 53 g rsa aad #8 i 1" REBEED i 8Z zzz 2 RE EEEEE ' g AnAanAmEnanE i zzz I 2} : ! Hi Li os ac osgia ndE ~i Hd i C iiiiid ] ?g ge s 8a32~~33 i 3 2 3 E=Ez i35a3z% a5iaEf i35aE38 i. ii 3 i 2 fo HUEEEE i i 2 2a a =a a A : ~ F35l0e RsisEteRd EDS 3of 2 5 iiiiid st 2 E oo oo oe oe 6 oo 55 ip pr 2 ga a nur a GBEE y 3% 3 FI eed 3 Bae gow 55 gp |BE dE HEL ~~ g 32z :z . 3 ozo: ozog . z ke me om 48 53 23 aa a 8 gE EE EIR : : g~ a 8 a% gv 85 3 i 15.8 27 gd of 38 hos TRIG i I$ AER ELLE ~ | .38, 222:23.33:2333 1 + F Fiaada 8go. os4 8 gs 3 8 3 = 3a EX i gfe 4h en dd ad ae sd 3g a gs: 553AE & Ii)s |3iEz3 : i: rB,R. oo a os os (Bgiadg 8 2F8305 3 LE&4 Ty=:g 2 ihe ~8 2 ~8 g 3 1 g F1H E of oAf aR l LaEa i i 3 Sis::oa @ FELEEELIB i : 3 33 3s 43 35 33 S83 : i a i Se s ~ sPei,n : oG uuF uE ungooi = 1 su PE 7 8 ii38 gg* <= 4 & & -~|v3 3% 8& TH 2a ~ 8g dJgi gd | F-25231: OneGenerationReproductionStudyinRats DuPont9763 -- TABLE 34 SUMMARY OF CLINICAL OBSERVATIONS IN F; MALE RATS Rove: NTu-1nber ofTRIats witVh IGiven VSiignl DOSE (mg/kg/day):N18 751 51090 351s00 OBSERVATION AHluonpcehceidaOver oo 0 o2 10 PSrteapiunteidalUndSeerpbaordaytion Complete 15 105 191 ios Heal 0 o 1 There were no statistically significant trends by Cochran-Ammitage test; p< 0.05. ~~ --~ wm -- `Company Sanitized. Doesnotcontain TSCA CBI 25231:OneGeneration Reproduction Study in Rats DuPont9763 -- TABLE 35 SUMMARY OF CLINICAL OBSERVATIONS IN FiFEMALERATS Roe: INIurTber ofIVR-aIts witVhEDGiven SViIgnI1 Dose (mg/kg/day):woos0 1785 5f0o)0 351040 OBSERVATION AHluonpcehceida Over Swollen Left Front Paw(s) 10 o0 10 1 1 o 0 0 VSawgoilnlaeln LpeafttencFyroCnotmpTloee(tse) 181 105 109 10 veThaerke were no statistically significant tren0 ds by Coch0 ran-Ammit0 age _ test1 ; p< 0.05. -- --~ Company" SanSsaniized. Donotecontsain TSCAcay H25231: OneGenerationReproductionSayinRats DuPont763 TABLE 36 SUMMARY OF DEVELOPMENTAL LANDMARKS IN F; RATS SREPUTIAL SEPARMTION - F, MALE RATS Dose (warkaG/rdoavne):: NEuIsber ofTI7fE5aTts witVhsLwGiven VS0iIgE0nL Mo LTB i onseryaTIONs ace (aye) 2Toaw msmee ewaeset a`s30asp VAGINAL EMTENCY - 7, PEALE RATS oosE (ma/kaG/raoavne):: HMTusTber of sats 5 witVhSEoGDiven IS3iT0gn0E Mos LW onseruatzons ~ az (payer aLamm maaosm nzass 3a.l7o6e6 Sate summarized as HSteamnassa peviation (n) . a b aToegtaecws"aidsiamyicta+ilc2c0aunltdaatybesyd =aasnAaglfeyoslildsoawysosf)u:csoivnagridaantcaepr(ecsoevnatrieadteisn: Appendix 3: body weight on the GNGoaalyy Sooffiganacichfhiiiecevavenemtmeennbtty aaannnaddlybbsooiddsyy wowefeiiggchhottvar6oinaanppcooessttnn(aacttoaavllardidaaatyyes23:85)).body weight on the -- % Compan Senizad.Doesnotconta TSCACBI 125231: OneGeneration Reproduction dyin Rats. DuPont 9763 ~~ TABLE37 TEST/ PERIOD SUMMARY OF HEMATOLOGY VALUES FOR Py MALE RATS Group I Omglkglday GroupI 75 mglkg/dsy Group V 500 mg/kg/day Group VII 3500 mekg/day RBCDA(xY107%4uL) 835 804 804 797% 027(10) 028010) 026(10) 0.1800) HGB (dL) DAY 74 158 153 152 149% 05010) 07010) 0510) 06(10) HCT (%) DAY74 63 453 451 ar 15010) 20010) 1700) 1510) MCV (@) DAY 74 554 563 s6.1 554 15010) 14010) 1510) 1.9010) MCDHA(Y2)74 190 19.1 189 187 --_ 05010) 05(10) 04010) 07(10) MCHC (gldL) DAY 74 42 29 57 ng 03010) 05010) 04010) 05(10) RDDWA(%Y)] + 128 125 129 140% 05010) 03010) 07010) 13(10) ARET (x10%4L) DAY 74 2042 1942 1810 1882 25.2(10) 302010) 20910) 47700) PLT (x10%4L) DAY 74 1251 1266 1224 1253 178(10) 145010) 860) 132010) - WBC IOV) - . DAY 74 1343605(10) 1345260(10) 1536568(10) 1639 3.03(10) ANEU (1040) DAY 74 207 1.68 176 228 076010) 0.6200) 0.6810) 07010) ALYDMAY(x7140%4L) 1199 1201 1337 1351 297010) 289010) 35010) 292(10) -- Tw -- -- `Company Sartzed. Doss not contain TSCA CBI JE25231: OneGeneration Reproduction Study in Rats DuPont9763 `TABLE 37 (Continued) SUMMARY OF HEMATOLOGY VALUES FOR Pi MALE RATS TEST/ PERIOD Group I GroupI Group V Group VII Omgkg/day 75 mg/kg/day S00 mg/kg/day 3500 mg/kg/day AMON (x10%uL) DAY 74 AEOS (x10uL) DAY 74 ABAS (x10%4L) DAY 74 ALUC (x10%4L) DAY 74 028 0.13(10) 0.14 0.06(10) 009 0.06(10) 007 0.02(10) 024 0.11(10) 013 0.05(10) 008 0.04(10) 006 0.02(10) 022 0.09010) 015 0.09(10) 009 0.03010) 0.08 0.03(10) 027 0.07010) 014 0.06(10) 010 0.0410) 009 0.04(10) ~~ Dua amanged ss: MSteaanndard deviation (Numberofvalues included i calculation) + Stisicallysignificant difference from control at p< 0.05 by DunnettTambane-Dunnettest. -- EC `Company Sanitized. Does not contain TSCA CB} 125231: One-Generaton Reproduction Study in Rats DuPont 9763 -- TABLE 38 SUMMARY OF HEMATOLOGY VALUES FOR P; FEMALE RATS TEST/ PERIOD Group Il Group IV Group VI Group VIII Omgkg/day 75 mg/kg/day 500 mglkg/day 3500 mg/kg/day RBC (x10%/uL) DAY 75 805 802 812 7.87 032010) 02510) 04410) 02510) HGB (g/dL) DAY 75 160 160 160 155 0.610) 06(10) 0.610) 07(10) HCT (%) DAY 75 454 453 459 a2 18010) 16010) 21010) 1600) MeV @) DAY 75 564 565 56.6 562 16010) 1300) 18010) 12010) MCHDA(pYg)S 199 199 197 197 ~~ 06010) 0310) 05010) 0610) MCHC (gL) DAY 75 352 352 349 350 0410) 0(10) 0610) 0.510) RDW (%) DAY75 1 10 11 1s 0.410) 03010) 03010) 04710) ARET (x10%4L) DAYS 1619 1673 1743 1666 29.5010) 37.710) 285(10) 31.7010) PLT (x10%4L) DAY 75 nn 1136 1140 1109 WBC (x10%4L) 1838) 1008) . 186(10) 168(10) DAY75 9.66 1188 1164 12.63% 1.74(10) 1.56(10) 25710) 248(10) ANEU (x10%4L) DAYS 097 0385 177 145 036(10) 046(10) 171010) 035(10) ALYDMAY(x7150%uL) 829 10.59% 933 10.59% 144010) 153010) 177010) 223010) --_ Tn Company Santtizad. Doss not contain TSCA CBI F25231: OnoGeneration Reproduction dy in Rats --_ `TABLE 38 (Continued) Dupon:9763 TEST/ PERIOD SUMMARY OF HEMATOLOGY VALUES FOR P; FEMALE RATS Group Il 0 mg/kg/day Group IV 75 mg/kg/day Group VI Group VII 500 mg/kg/day 3500 mg/kg/day AMON (x10uL) DAY 75 AEOS (x10%uL) DAY 75 ABAS (x10%uL) DAY 75 ALUDCAY(x7150%:L) 0.15 0.05(10) 0.13 0.0410) 0.06 0.04(10) 006 0.02(10) 0.18 0.06(10) 0.12 0.03(10) 0.08 0.03(10) 007 0.02(10) 0.25 0.15(10) 0.18 0.08(10) 0.07 0.02(10) 00s 0.02(10) 0.25 0.13(10) 0.19% 0.06(10) 0.08 0.0410) 006 0.0310) --_ Diamangeds MSteaanndard deviation (Numbeorf valu included in caleuion) + Sttsiclly significant diffrenrcome control tp< 0.05 by DunnTe ahDunane st. --_ 9 Company Sanitized. Does not contain TSCA Ci F-25231; OneGeneration Reproduction Sudy in Rats DuPont9763 --~ TABLE 39 SUMMARY OF SERUM AND PLASMA CHEMISTRY VALUES FOR P;MALERATS TEST/ PERIOD Group I Group Il Group V Group VII Omgkg/day 75 mg/kg/day S00 mg/kg/day 3500 mg/kg/day ASTDA(UYLL7)4 ALT (UL) DAY 74 SDH (UL) DAY74 PFLU (ug/ml) DAY 116 10010) 3 4010) 109 43010) ol 0.0(10) 85 1510) Me 710) 146 6.1(10) 01 0.010) 81 19010) 39 13010) 148 55010) 02@ 0010) 80 12010) 00 6010) 126 4.100) 04@ 0.1(10) ~ Dua sanged as: MSteaanndard deviation (Numbeorf values included in calculation) @ Sutisticallysignificantdifference from conzol ap < 0.05 by Duns fest. --~ 55 Company Sanitized. Doss not contain TSCACB H25231: One.Generation Reproduction Study in Rats DuPon9763 --_ TABLE 40 SUMMARY OF SERUM AND PLASMA CHEMISTRY VALUES FOR P; FEMALE RATS TEST PERIOD Group Il Group IV Group VI Group VIII Omgkg/dsy 75 mg/kg/day S00 mg/kg/day 3500 meke/day AST (UL) DAY 75 ALT (UL) DAY 75 SDH (UL) DAYS 91 1610) 36 10010) 132 23(10) 83 1710) 4 1410) 145 3.100) J 11010) 35 610) 153 3410) 102 4510) 49 3100) 193 14.7010) Datsaranged ss: `MSetaanndard devition (Numofbvaelures included in calculation) ~ # "STuhteirsetwcelrleynsoigsniaftiicasnctadliyffsrigennicfeicfarntomdicfofnetsroelacaet fpr<om0.c0o5ntbryolJoantcpk<he0e.r0e5.Terpsiza rend test. *@_SuSuitsitsitccalllyy ssiiggnniiffiiccaanntt ddiifffferreennccee ffroomm ccoonnttrrooll aatt p << 00..0055 bbyy DDuunnnest/teTsat.rmhane-Dumett es. --~ we -- `Company Sanitized. Doss not contain TSCA CBE H25231: One-Generation Reproduction Study in Rats DuPont9763 TABLE41 TEST/ PERIOD SUMMARY OF URINALYSIS VALUES FOR Py MALE RATS Group Group I Group V Group VII Omg/kg/day 75 mg/kg/day 500 mg/kg/day 3500 mg/kg/day UFLU (ug) DAY 116 12.1 4.1010) 539 93(10) 176.1@ 385(10) s124@ 109.5(10) Duasmngedas: SMteaandnarddeviton (Nomofbvealures included in calculation) @ Sutistcally significant diffrence fromcontrol at p< 0.05 by Duns es. --_ ~~ 7 -- Company Sanitized. Does not contain TSCA CBI g 4 ~| J .8.3 3.8 3.3.3 FR gE 35 35.89 4d JS 4d ds 4d 3 2 3 2 ; 153333 137% | sp imoannmnunny |! zs 38 49 44 29 44 dd Hd. dd ds z 118, 2 a gpreriggalg} Pf8y FUT JtHE g Bie gn iRaTEI ATER EAE 43 gz = cE 22 :| ` g - 245 3 ud a 22 2 Iii ~g 2 z 2 2 3 3 a = _3 =gags | sjmafiuHEgaE i if i _ TF2 r9;mfp8uraRoaEoeR:gLrgReaYs i 3 Eg = iz: 2.8 3 3 8 8 3 8 ff BIA EG 1 gs 3 :f i 55 fF 88 8 % ~ : 23. 2.33 2.3 88 gd Fe ge 89 ga 4 i z if 38 S= 1 = 2BE 2& 28 8 5he3 | "S:p iE2i%LaSsI3 E8E2R2E8 &RhEAL23RE22 iaf8sg!0 ii ~ | SSgpyogg" TgsFgs nogoo ogee 3Eho: 5 $B8r9g Figg i|d Eluss TEinBEERERD i: g | [Bom s g Es 3 & ER EER C8 $3 Eats : 4ig THa E08aRgE 2EgEE|s8 Lf8i8d:es8 g PE i fei Eff igh ~5 ] 85888 L Hoimnad nd pd ud ad n i; 2 3 | ~ jgeegt # eral Bi! iin s ni EEf EEt n L0id fq 7 i Pi in i: P FouiptrEbRepiiE d apLsd E nH ; $8 5 & ji ~g 3 : 2.8 8 8 8 Is 3f 0% 2% 2% 33 33 82 ATE ES IIE g3 g i : Si gt i gyn : EE REEEE EE ~~ 3S g 8 gz 4 gg 588 8 g i g 27 2 : gl. gE so . . g 5 2 8 go 8 ~8 2 5.83838 : Io 33 82 gz 2: 29 3 2 oe Gzi8ia2ra8ay ii.d8 ii 3 #7 AT is i "iad ii 2 TE f8 r sBf oE f aE f 2%Nan fs 2 gs gi +e gs od 2d saad C50%2 i 143 43 zi E:F ou Hi gHlIial ~8 i 5 & 3.3.8 8,3 3 : ] 3 ; 38853833833 i EI ERE BE Ra i _ PEE gR f, g oF 3 3% 8% 4% B88 38 EY , Pld ) 3 5i i EERE EERE 3 ~3 ~f i g 8 332 38 23 2 BEER EEE i 4 2 = i : fz 35 58 EF 55 3 55 35 3 ad 33 38H gi 8 11:FE JE MNNNULIER f2%eg8ln mmEEan s 8& % =fg& 88 8 8 3a a i . 8 i PoE : Ce Li Borgo fg BL ~ i ~| 30% 3 8.3 3.3 z BR 23 ga <c gx 3% dd 8 : sssszszg hi |} IEFEERE i 1 138383533 3; i fEpTEETESES LH], 4 i2%t 25s 825 83.8 5 338 85 33 gS5i8e2 s2 Fis C8S 2J7n f5Ed sgRd dosa g3hs 3Ade s3a% aae3]) SLiiE0oD n0 I3 EE ikRe ~3 EE "i 33: 333 : : Bo TalaEt R0hREniUnAEul i: gE cQEginunun ~ | 3E k E gE " 8 iris 83fif.7e igifaiddfsgs i 2 o5 &r | | 3I Cea I ge 5 2 E ~: | ~f IBs E3 REgEEE4R5 EsIo zEEg iI 2 gs 5 8 8 9 i Elsie I 2o it RIELEEEE "gi . ff Jl NHILIEH 228 z333 33 gy T HE : zg g 3 i] E 8l 83 e 8 d ~13 || ~8 E| 2 7 3 of ss oF uf5 23 53 =8 2g Co :4 ii 3 FPaigd Adi i 4 3333.3 `i i ~ sf BEUC if e ggg, go 2.22.2.F i EEE 28% 1 1x | & El ily 8 gli is ~ FgE H: IIEd ~ 2 | | 52 i |i 2 go : 2 38a} wo on soo eo soe | z ESEi ii ~~ g: g 3 Beal oo ooo om nome ee i , FE Co gsi 3 g ulAl P[ei Z g= : Ni i i PE &| HI g Eid ~ ii GpAg gE gaEinpg0 :32 i i 8 = : ~~g Po ; ET | ~ SE fie oo Lg2oE, Rafer - i g i. |i 5 5 Ig i : gui Pe : zi | ; |i: iLEd mn ilo ii HigEusRoEf HE pr ~gj al & : || || :! 5gE i : gs H o : u 5 Ix: PEBE | i! hoardLLid & lig eg ~1 HEE ~8 3 5: ~~ FE ale [ ER4 ii i i 8 gi Pog 1 2i i. E poIr |i 2CdCE ; hy| i idl i: : | ~ 5g z . : 8 HE i 5i : a id i eo s E. 1 | --~ Hg desi ol 241Po1Ek 32 Zgii giE| i : 8 z i it i Po & gd ~8 iad ~8 2 . |; |; C I |i |; 1 ~ aEBE o. E i R i 1 fu 3 ini gi id od ~1 HEE i | &i hi or,Le = gil 5 BE 83 | 2 8g ii i i " ' ~3 : 8 El i i i hd. r i1g1 i gi PE EfE e+jEcE: 1a81E }: a 2127 (HE poof ER EER g 2 i1 P {45s4 2 g fl PEE 41 5Eigmsf H Pfaa8Edse : Lh PE . gE} {ee 53 HE] id 3 ~1 BEd ai 8: 3 i i 8 i id i SEhCi,ro in 1i g HE PiE sa 2 i1 jHdEt ~ q fesic coc ighgd 5 2 EZ Eo o- P88 ER i gisE. Piike i 2RbEh HE PEE i = 1 g uflag 3d JPiorhil ---8 Bl aii) BE" 8 BEio:z "og 5 8 I TR om d i Ea ih } g Chala Tam ann ~ | g8 11% 111 y BE aden Gala i mam cw CI EsaLELNd.EE1RIE ou odie ow ddll 12 DE Gl lawl Bild ~ ii a 2 E E 8 8F 211] i igd ii | , i =H i ir #1 i Zor i 5B, | i HI & - 2sg 013 0 gt 5 . 5 BCrael wo ae HRGMlgE gil lh P oogdm omo#pif l4 oaEkPR BEER IRL WIoRpF IIE td m a ~3 geo Ee | ig :olrimn oot i Po :| ! 01 i g Ey om. gee oh ee yi p1 oEmd. be 1rH g gagl BBH E 21:| dBgELlidiaih a1k1m : JER EE ~g 8 7 2i s Po ; Eni 11 i 7 ih 3 phy lal ge Eei ies ii AE 10g ,i i5b :!g B32ah| hJi ) Fl | oseh 3:] z[iEI gE aely 1HgI i gi Ll Si ~8 EE | img : 4] IW ; } S.0 iid } 8 Haai on wml gn eee ean g for} a wo E oe LEE i borelomigd oo gdm a i 5f 0 gg BhOi uh:gf oi pgioE gay aeoirlHbs of pian,  i| : Po fs 2EE11l87ai 0 | ces 3B5ad ~1 i fh F8 l8Eu0e0i i Hp5k5l38 g J f Bl EE En 0 Buon :: fyPoHah NhiEs, EH :i g a Bly m am foBiiaiw: j nim aan ~3 Brie i ii : . EL. : P08 i i CgLi | i Feo H Loe ogy ow ya gE. 4 gid UAEI EI [HA i3go| i1 g i: J1 FfaE mambaiglciog,HE0HB Ep ii, mr ~ Fo : Sg I| |2 i PH : i 5g i Z i 0 iil i Eh i ga, FI Tog48g...lueF ~ 1 sam Ei fim 34z FgiHgl3Talf 5 iSaEdE FI hil EEE biksi phy great. :i wr | 3 gl EEL LL :: |i i wo Hi i 2: or EL fake ~| geB fmuel cro womans on|To eee iid gr ow | ind Zi i hme AE i : &I uli WwoooBn BaEd 3 Eki, gi Ea D1 o5egsopo :d dlis i dHgmehl HfEi faimgeE =| Bl 3 i HL25231: One-Generation Reproduction Study in Rats --~ DuPon9763 APPENDICES --~ --~ Eg - `Company Sanitized. Doos not containTSCA CBI Ps APPENDIX A ANALYTICAL DATA -- TTT TB CompanySeniasd Dossnorconan TSOA CH! --~ "Table 1. Concentration VerificationsndSabiofli25t23y1 inDosingSolutions PSreapmapralteioTnypDeay Nominamlgm 223M1e)ssured N= ominal TestDay 2 ConcentratiCoonnVterroiflication ) 00 ND -- 151 862 1511 936 574 4 1512 pn Mean: 872 sis 680 152 18 853 Mean: c10v82.29 0, 11000012 91162 997126 Mean): 9c4V4v2.a4%0 10 7001 00211 7oss 190621 0022 638 Mean: 68 912 05.9) ~~ Mean: 6c91s2s33 08) Subiliy 15 1050) 70 010 7859706) 11084 Test Day? `ConcentratCioonnVterroilfication() 00 NDO) -- 151 26 1511 128 840 883 151M2ean: 112217 87 647) 115522012 115620 11001637 Mean: 156 avs) Mean): 1c42v2.20 oi 5HourRoSoumbiTleiy 15 165 1100 "52)%DDuopiinsnslpoiecsproevne wcermegcayn25a23r.mMaL aies5.dnnoannd,mClV.doc se volaume.fol vHeSr2ylu3f5oeod efmei -- ~ ()))MMDainnerreennnotttdffeoortaalsnldsymlsyeonsdanurpieasasmpplles.. PM retfo uphnterembyesof inlsample. Original alysisnot epidue1aliquotcor rs `CompanySaniizod.DossnotcontTEaCAiCBnI $:25231: One-Geneaton Reproduction Study in Rats DuPon.9763 --_ "TableII. Concentration Verification of H-25231 in Dosing Solutions PreparatiDoany mg/mL 252312) Percent S"aTemsptlDeayTy4p6e `ConcentratCioonntrVoelrification() Nominal 00 151 Measured NDO) 151 Nominal -- 1007 152 Mean: 1I6569x11 (110160.70) cv.7% 11000012 3mn 11112300 Mean: c1v3.10%7 (113.0) 700-1 9 1070 700-2 666) 95.1 Mean: 708 +59 (orn Test Day 114 CV.8% a ConcentraCtoinotnVreorlification() 00 ND) oe 151 152 165 1100 1290) 862 `Mean: cv1.41.772%25 (98.0) 11000012 112007 11027000 `Mean: c1v1.4s9.%1 (114.0) 770000-12 87615 1902933 `Mean: 7C2v3.85%9 (103.3) A) (8) HDoasisng!sai uionconcn -- mg 1.252-- 3mL ed> on ml. dose vou: Duplicuesamplepo evelwer anya. Mean...1nd C.V. calcio -- verity uniforofmmictry. D ( DMenesenlotfdoedtuepcl.iste reyofoergisnal sample. Oil sys ot pore de 10 lqot rs rr `Company Santized. Doss not contain TSCA CBI 0 H25231: OnGeeneration Reproduction Stady in Rats --~ Figure 1 Representative Analytical Calibration Curves 22200000]] EYq=ua5t0io7n6fo4r2th4e2fi6e1d6l+i6ne7X: . "a0 R-Squared = 0.952860 ~ i0 DuPont9763 Concentration, ppm . Figure 1a: Ctaolriebprlaitciaotnecpueravkea(rLeaC/mMeaSs-urC6e-mCe6n/tbsis(s)qsuahroewsi)nfgorlicnaelairbrfaitti(olnine) --~ solutions of t0 0.74 ppm H-25231 (0.00024 dti0l0u.te0d00o7v4ermag/comnLc)e.ntration range of 0.24 $e `Y=Eq9ua2ti2o1n 5fo9rt+he3f7i3e1d31lin*e:X 2500 R.Squared = 0.997615, 32 0 I EEConcentation,A ppm Figure 1b: Ctaolriebprlaitciaotne cpueravkea(rLeaC/meMaSs--urCe6m-enCt8sbi(ss)qusahroesw)infgorlcianleiabrrfaitti(olnine) solutions of H-25231 diluted over a concentration rangeof 0.24. 100.74 ppm (0.00024 t0 0.00074 mg/mL). -- Br -- Company Sanilized. Doss not contain TSCA GEl H-25231: One.Generation Reproduction Study in Rats -- Figure 1 (continued) Representative Analytical Calibration Curve m0] `YEmqoua3t3i.on4f6o1r7t+he1f8i2e6d.1l9in+e:X R-Squared = 0.998816 i 1000. DuPon9763 Concentration, ppm Figure Le: Calibration curve (LC/MS -- C8-CS bis) showing non-linear fit (line) to replicate peak area measurements (squares) for calibration solutions of H-25231 diluted over aconcentration ~~ range of 0.24 to 0.74 ppm (0.00024 t0 0.00074 mg/mL). 700] `RE-=qSu-qa1utai3or.ne7dfo2=r3t0+6h9e81f70i19tt11e.5d2l8in+e:X gw Concentration, ppm. Figure 1d: Calibration curve (LC/MS ~ C10-C8 bis) showing non-linear it (line) to replicate peak area measurements (squares) for calibration solutions of H-25231 dilutedovera concentration range of0.24 t0 0.74 ppm (0.00024 t0 0.00074 mg/mL). ER---- oesnelconEWTSCACEL 125731 OGneneration ReprodSiysinaotns Durensres --_ Figure 2 Representative HPLC/MS ChromatographyChromatograms cSomegmiSsoen,201 : User: ve 05fary-t2e00b2l1:i0nn6:sg58 co;Iho rSn 5 [rFTee = --~ commin 5 10)j O|F Trams98:8477 cou 5 ras: seesid ns] F wS T ee R ve Time . i Figure 2a: Representative HPLC/MS chromatogramsof 0.00 mg/mL dosing solution of H-25231. =A Company Sanlzed. Doss nocontain TSCA GBI 25231: One-Generaion Reproduction Study in Rats DuPont9763 PN Figure 2 (continued) Representative HPLC/MS Chromatography Chromatograms 0502021687 Smoath(tn2:3) ha * 05020257 Smoath(th2:3) 100: 780 SIRof 4 chann78e9l.5s0:8 1363708.12 928504003 ass SiR of4 channe8l8s9056- 736 122804004 177720 050202%37 Smooth(2V:6n) 1 ~ 798892 SIF of 4chamel9s8.3.S08587100003 90195 o 050202657 Smooth20) 10 : * 256 5% 954 min 1089SIR of4 chann1e0l8s6E.S04523 347704003 40450 956 5% 500 min Figure 2b: Representative HPLC/MS chromatograms of 0.50 ppm (0.0005 mg/mL) analytical reference solution of H-25231 --_ 5 Company Sanilized. DoesnotconI tain TSCA CBI H25231: OneGeneration Reproduction Study in Ruts DuPont9763 --~ Figure 2 (continued) Representative HPLC/MS Chromatography Chromatograms 05020242 Smooth2) To ot 0502023042 Smoath(h2:3) h 768798 1730.45 s80 1978346.45 SiRof 4 chann76e9l.50s-8 111604004 910 min SiR of 4channel8s89.50-5 120004004 050o2021042 Smoot (2:3) --~ * o 0s02021c42 Smoot(h 2) 100: * 04 SiRof4 channelsEmSi-n o7e83 7.1139084900063 1118.16 540 min 1088SIFof 4 channe1l0s8.0.S0-4 523 38504003 64384 952 25% 3% 12) 550 Figure 2c: R`enpormeisneanltactoinvceenHtrPaLtiCo/nMoSf 0c.h5r0opmaptmog(r0a.m00s0o5fm1g0/0mmLg)/omfLH-d2o5s2i3n1g.solTuhteiomnedaisluurteeddto concentration of the representative solution is 112 mg/mL. -- [E] `Company Saniized. Doesnotcontain TSCA CBI 25231: One-Generation Reproduction Study in Rats --~ DuPont9763 --~ APPENDIX B INDIVIDUAL BODY WEIGHTS OF Py MALE RATS --~ F3E Company Sanitized. Does no-- t conta-- in TSCA CB 125231: OrGeeperation Reproduction Study in Rats DuPont9763 ~ INDIVIDUAL BODY WEIGHTS OF Pi MALE RATS EXPLANATORY NOTES Notes TestDays 1-75 = Test Days 76:90 = Premating period Cohabitation period Abbreviations AK = Accidentally Killed FD = Found dead SD SE = = SSaaccrriiffiicceedd ibnyedxetsriegmnis; data excluded from group means. (Group 1.0, Animal No. 657409) - = NoDaa -- --_ e ese eeeseeer e Ed `Compeaenty Se ae niized.b Doss noe t contain n TSCAGB 25231: One-Generation Reproduction Study inRats DuPo:9763 -- INDIVIDUAL 20DY WEIGHTS (grams) OF P, MALE RATS GROUP: 1-0 DOSE: 0 MG/KG/DAY onaTvEsST: 1 8 15 22 29 36 a ANIMAL NO. 665577339921 665577339903 665577339956 665577339978 665577349090 665577440012 665577440043 665577440056 665577440078 ~ 665577440190 227898.l56 333335..88 337844..75 442241115 445635..29 447880..81 459052..37 320720)35 336210.000 430837..79 443883125 446752..71 4S8058.93 452995052 2278421131 332221..22 336523..20 440003010 442341103 44sse2l.38 447@4nl.S7 2286080090 332103..14 334586..27 3389251.3 3492631103 441s45..65 443@60..98 227853.099 332266..41 337604..36 4400271.28 4433851.36 446602..09 447799..61 229692..40 239347..72 337324..37 4316070.68 444051136 442741.56 449a02..39 2278720.74 334169.040 338967..84 4405421016 443972..35 452499..18 45543..91 239753..49 335191..05 431800..10 44146..62 444875.52 541833..22 553153.040 228739..42 334233..60 339623..85 433859..53 446188.165 449466.195 456146..36 220656..30 334154..17 339509..54 44303L.55 442891.43 544081123 4562951.37 --~ 8 Company Sanitized. Doss notcontain TSCA CEL 125231: OneGenerationReproduction Studyin Rats DuPont9763 ~ INDIVIDUAL BODY WEIGHTS (grams) OF 2; MALE RATS Grove: 1-0 DOSE: 0 MG/KG/DAY onDTAeYsSt: 50 57 0 7 7 os 52 ADH No. 665577339912 657393 5$2502.016 53203 5s3s0a.93 5512 554753..59 568.8 5s488L.76 576.2 5s3e6d.l80 S615 554982..83 594.5 656033.14 609.9 666555777333999546 S$5250045 ss2ealls5 5s9a1s Gs0s27.0 5593801008 6s1a0.l5 s6e2s1ls0 47s soals 528.5 537s S172 S422 5s12 665577339987 657399 45181l035 S214 s53e2l0s5 sis.4 e54r9.o7 536.4 a56n0d.s3 5427 d5e4s6i.s0 53219 456189.24 550s 458745.79 557.4 656577440010 657402 2S10660 sss s20i.s5 48al0 553277.21 49610 533499..08 504.7 553405l.04 4%8.6 556358.30 517.3 S58T6.L3 53.7 665577440034 657405 6Se52.l5s Sez 46714147 sels 468276..77 5996 S65011.21 609.0 560535..32 607.2 469771.16 617.4 569058..46 637.9 656577440076 657408 SSiuolle1 43s ssss7.a8 40s 557861.91 5021 559922..88 511.6 559974..9 503.6 660281115 5215 664133..06 533.7 --~ 656577441009 5d3e5s.l47 5s301262 SE51(0D.A3Y 60) 518-.5 513>.8 526-.6 5402.8 --_ 9 `Company Sanitized. Does not contain TSCA CBI F-25231: One-Generation Reproduction Study inRats DuPon-9763 ~~ INDIVIDUAL BODY WEIGHTS (grams) OF By MALE RATS GROUP: 1-0 DOSE: 0 MG/KG/DAY onaevsst: 2 106 13 ANDHAL NO. 665577339912 665577339930 665577339956 665577339978 665577349090 665577440012 665577440003 665577440056 665577440078 ~~ 656577440190 567240.025 569311..36 564909..86 SSDD ((DDAAYY 111144)) 661492.020 661525..15 663635..47 SSbD ((DDAAYY 111144)) 5578221028 559776..93 650894..93 SSDD ((DAAYY 111145)) 458060..50 469051..28 560103..56 SSDD ((DDAAYY 111155)) 557686..22 556779..27 558759..93 SSDp ((DDAAYY 111155)) 553878..80 559425..71 650469..15 SSDD ((DDAAYY 111166)) 7501070.62 571297..90 5724090.01 SSDD ((DDAAYY 111166)) 666511.056 665791..58 666842..67 SSDD ((DDAAYY 111167)) 653376..80 654360..77 656338..35 SSDD ((DDAAYY 111177)) 547-.9 553-.3 550-.1 SD (DAY 117) --_ To -- Company Sanitized. Does not contain TSCA CBI 25231: OneGenerationReproduction Study inRats DuPont9763 --_ INDIVIDUAL BODY WEIGHTS (grams) OF Py MALE RATS -_ GROUP: TTT-0 DOSE: 75 MG/KG/DAY onDTAEYSST: 1 8 15 22 2 36 a ANDHAL NO. 656577441167 66537744118 665577442210 656577442232 656577402254 665577442276 656577442289 656577443310 665577443332 ~~ 656577549365 222786108...994 333022620..0803 335690..16 344.7 333799841...630 4421581.38 4090 443491..21 4390 445595..60 450.2 220748..45 29.6 332120..55 335.9 335568..65 380.7 339904..36 41318 4422170.00 4d8ls 445570.070 4s1i2 44686L..15 5145 220603..13 265.7 239257..01 3345 336363..37 39.1 430589.051 432.0 434808l0s 46316 447063..02 4se.2 44926..46 518.1 236137..94 26205 239775.03 3316 344a31.s2 379.0 347968.177 409.0 4s0378.l46 4asl2 453737..06 47915 462513..16 S016 220692..50 273s 336227..06 333.0 431668..66 378.9 437952..98 421ls 5413281176 460l8 5a6s26..3s 496.1 Sd6s1ll1e 524.9 92050'.s7 302.2 335361.16 353.1 430894..65 406.4 445246..44 44917 S47012115 48312 553088..91 509.5 556372..91 534.5 226417..85 229741l.s7 2392970.34 332551.s0 3M5i01d5 336952..73 347056..17 --~ Eo Company Sanitized. Does not contain TSCA CBI 25231: One-Generation Reproduction Study inRats DuPont-9763 INDIVIDUAL BODY WEIGHTS (grams) OF P, MALE RATS GROUP: TII-0 DOSE: 75 MG/KG/DAY oxDTaEvSsT: BE 57 6 n 78 85 02 ANIMAL O. 665577441167 665577441189 656577442210 656577442232 665577442245 665577442276 665577442298 656577443310 665577043323 ~~ 665577549365 447775..85 448879..28 550025..10 551281..96 550149.199 551355..26 552560..60 457006..30 458202..50 458385..26 459564..17 454550.137 459571.03 55602215s 457288.037 45s4a8..l5 551701..25 551805..63 S508s4l.48 553901173 s60a01e1 45s166..65 456355..20 45793..10 459760..16 456640..51 458851..30 559062.62 S6i5050.06 56883..87 576095..80 75291155 7S0681.24 7527221.38 7548391.26 4528111.70 458471..79 s50526..04 SS6u2l1o 5S602s1l8i 558224.88 5549010178 550816..42 562104..25 564317..72 s64429l.a7 654435.00 s6s531i.28 5676020.08 554543..14 555772..00 559729..14 650979.186 6600521.94 G6l027l.12 661171.197 650508..22 652707..69 655938..45 661753..15 660794.56 66192.0 6693151.84 432901052 443080..40 440499..33 4450091.01 4450961.70 447153..32 44715896 --~ 3 CompanySaniized. Doesnotcontain TSCA CBI 125231: One-Generation ReproductionStudyinRats Dupont9763 --~ INDIVIDUAL BODY WEIGHTS (grams) OF Py MALE RATS GRovP: 111-0 DOSE: 75 MG/KG/DAY onaTvesst: 9 106 13 ANDHAL NO. 665577441176 665577441198 665577442210 656577442232 665577442254 665577442267 665577442298 656577443310 665577443332 ~ 656577453956 557316..11 554764..48 558562..96 SSDD ((DDAAYY 111144)) 558116..01 559247..72 560330..02 SSDD ((DDAAYY 111144)) 651368..57 652378..77 653517..73 SSDD ((DDAAYY 111154)) 6S1102.)7s 651265..72 653269..56 SSDD ((DDAAYY 111155)) 7660311.30 758937..61 579954..61 SSDD ((DDAAYY 111155)) 05552.080 S86. 655199..42 593.5 651599..69 SSDD ((DDAAYY 111166)) 609.2 SD (DAY 116) 662836..30 6638781.83 674190..53 SSDD ((DDAAYY 111166)) 7622551.36 675421173 7654091.85 SSDD ((DDAAYY 111177)) 4696120.14 567055.98 561746..73 SSDD ((DDAAYY 111177)) 42707 347 ddsie so (av 117) ~~ 3 `Company Sanilized. Does not contain TSCA CBI 25231: One-Generation Reproduction Study inRais Dupont.9763 --~ INDIVIDUAL BODY WEIGHTS (grams) OF P, MALE RATS GROUP: V-0 DOSE: 500 MG/KG/DAY onDaTEySsT: 1 8 15 22 2 36 a3 ANDHAL NO. 665577444421 665577444438 665577444456 665577444478 665577444590 665577445512 665577445534 665577445556 665577445578 ~ 665577445690 228489.082 323708..63 336038..93 430360..96 433458.145 436579..77 438535..56 228808036 333277..04 338753..42 44l1a6l2s 444449ll3z 447899.139 550180.036 2205760.82 324879.23 338292..54 434273.20 436661.35 g38o4.l6 531929..35 227764.81 331103.88 334477..66 336B9L159 441051.49 443422..32 445617..37 22s884'06 333063..73 337584..49 432809..36 446138.127 447483.07 446g28.l72 225808..58 333398..22 338940..99 443218.164 4a6e991l37 540s3a62 55313875 226991.37 332187..75 337622..24 430909l.a2 a43l01l4 44467166 448802..99 2269831038 239253.55 332776..08 344085.158 343654.82 346822.34 439878.i7 3226440036 337020..11 433431..64 4388B2L.l8s 542270.173 546491.34 549643152 227850..60 330191..76 334521..55 339608.21 347171.i0? daoallas 4g2e1l9z -- a `Company Sanilized. Doesnotcontain TSCA CBI H25231:OneGenerationReproduction SudyinRas_ DuPom9nes ~ INDIVIDUAL BODY WEIGHTS (grams) OF Py MALE RATS Grove: v-0 DOSE: 500 MG/KG/DAY ovoTaEvssT: 50 5 "n [3 os 2 no xo ss8577444412 857443 s3o733.44 Sous es10s.2 saa 955:.249 59307a d52e0s.l9 massless 533955.87 sse2 a5o3a9l5s 632 8es577a4i4s4 657446 S53i00e6 433 5S7493042 an; sSsm1s2 aris 6s0esl aaa 95419.73 aril e54i7s7 4s 651656..90 ado 663377404487 657449 i69i0s1 30300 sdieoallss S100 ssolelles S247 ssus2 S430 s51a3s7 sanz 5s2a2os sels s54i7n8 548.0 656577445501 637452 3i0ss S003 sseilss saas Ss02a3 sel Se12374 S661 aelleos 552.6 1sl80lss 570.2 56166s3 566.5 663577445334 67435 li9i173 49512 4s7l90o3 4zel0 ssoeuds ajmls S54136.09 adsi3 55329758 aen7 5S306.28 ase. 5s4e6d.i0s 66.0 885577245376 857458 5678.125 43.3 s63i0e.03 49103 saiess soe 5e52z.3 Saez 5659026 5163 5e5667.27 se 565189..55 532.7 ~ 885577245690 $73831105 a9a510l7s d4s5o1.4 457065..40 44753031 447B6e.74 |AK49(7D.A8Y 86) --~ -- ws Company Sanitized. Does not containTSCA CBI H-25231:OnGeeneration Reproduction Study in Rats DuPon9763 ~ INDIVIDUAL BODY WEIGHTS (grams) OF P, MALE RATS GROUP: V-0 DOSE: 500 MG/KG/DAY oNDTAEYSST: 9 106 m3 ANIMAL No. 665577444421 665577444430 665577444465 656577444078 665577444590 665577445521 665577445503 656577445565 656577445578 ~ 665577445690 45338'.s8 4514051.37 4515530.56 SSDD ((DDAAYY 111144)) 6528000.27 6548561.33 658751.27 SSDD ((DDAAYY 111144)) 4508301.46 e5s7e8l.o3 4557821.77 SSDD ((DDAAYY 111154)) 555440..37 556438..07 556587..39 SSDD ((DDAAYY 111155)) 552568..29 557401..57 557423..41 SSDD ((DDAAYY 111155)) 567850..22 568462..24 565939..04 SSDD ((DDAAYY 111166)) 557545..39 5577241.60 558841..40 SSDD ((DDAAYY 111166)) 546760.16 456861.10 547808.l8s SsDp ((DDAAYY 111176)) 563989..16 571503..48 7525940.12 SSDD ((DDAAYY 111177)) 510~.9 524-.6 530-.9 SD (DAY 117) 3 Company Saniized. Does not contain TSCA CBI H25231: OneGeneration Reproduction Study inRats DuPont9763 --_ INDIVIDUAL BODY WEIGHTS (grams) OF Py MALE RATS GROUP: VII-0 DOSE: 3500 MG/KG/DAY onaTvesst: 1 8 15 22 29 36 a ANIMAL NO. 665577046667 657068 226675..42 227810..44 331069..03 336305..60 335727..75 339732..85 432649..24 286.3 283.8 324.1 324.2 365.6 406.0 433.8 665577046790 657471 2259570.15 3703 321887..40 2937 334145..32 302.0 3373070.64 322.9 338489.32 337.7 43138.25 350.7 43378120 352.0 656577447732 657478 2299090'53 332421l.94 336762..11 4309s7l.20 4430911197 44532001 4648s.24d 3700s 3147 336.0 365.7 38911 409.7 424.5 665577447756 657477 82681'.s0 S010 238360..60 347.7 335055..12 391.8 332520..78 436.9 3338831137 473.6 335886..51 430409..14 478.6 AK (DAY 42) 665577447798 657480 227795'107 328236..46 336396..26 430684..26 434818l1s5 34689iss 448081.37 287.8 318.8 362.6 388.4 a18ll 4222 435.1 665577448812 657483 22973a0l28 32935.90 338393..05 4335851.01 4377461132 530803.73 532934.55 28108 328.9 383.7 413.0 44als ad9l4 466.0 ~ 665577448845 228872..80 331236..27 333544..08 3388350.63 43928l162 44138.48 442587.16 --_ Ea Company Sanltized.Doesnotcontain TSCACBI 25231: OneGeneration Reproduction Study in Rats DuPont9763 ~ INDIVIDUAL BODY WEIGHTS (grams) OF By MALE RATS GROUP: VII-0 DOSE: 3500 MG/KG/DAY onaTvesst: 50 57 6 7 7 8s 92 ANDIRL NO. 665577046667 43583a.l9a 4397350.15 437980.02 439946..70 437579.188 349921.10 439951.169 665577446698 446233.010 448a5a.l1s a5c0o3l.o0 s418i0llss 443s72.l84 447508..38 44a822..80 656577447710 338531075 33692..22 338638..69 339774..95 338185..80 433176..66 432666..64 665577447723 aas7s8l'95 549030.045 551067..41 550370..30 5501351.11 550200.049 551321.14 665577447745 a37s0l0o9 431901l181 433996.55 440a90ll60 440338.63 442042..87 434909183 665577447767 419-05 437-.3 451-.7 453-.6 45-10 439-.2 46-1s 665577447789 539173..48 543131..92 544104..69 451521..82 544039..37 545299..05 547139.66 665577448810 439370.035 455205..40 456665..47 458900..50 455604.82 465036..01 462772.85 656577008832 657484 46024025 447273.l46 444997..47 FD45(4D.A1Y 66) 460-.2 481-.0 494-.3 436.9 456.6 490.5 484s 48410 473.6 4gslB ~ 657485 43107 aes? as2l6 4s0l3 47219 4870 43Ti0 --_ as CompanySanitized. Dossnnotcont!in TSCACBI 25231:OneGeneration Reproduction Study in Rats DuPont9763 --~ INDIVIDUAL BODY WEIGHTS (grams) OF B, MALE RATS GROUP: VII-0 DOSE: 3500 MG/KG/DAY onDTAEYSST: 5 106 13 ANIMAL NO. 665577446676 665577446698 665577447701 665577447732 665577447745 665577447767 665577447789 665577448810 665577448823 ~ 665577448854 450085..81 359296..84 451121..52 SSDD ((DDAAYY 111144)) 540346..17 419605..07 449671.36 SsDD ((DDAAYY 111144)) 4317990127 4372511158 433803..02 ssDD ((DDAAYY 111145)) 5522040.57 549253179 549373.32 sSpD ((DbAAYY 111153)) a40s6l1]7 443282l1a4 444228167 Ssbp ((DDAAYY 111155)) 48-17 451L07 4710:7 Sp (oAY 116) 452678..40 452960..29 462084..68 SSDD ((DDAAYY 111166)) 643882.069 646501..54 646775..74 SSDD ((DDAAYY 111176)) 501~.1 492..1 492-.3 SD (DAY 117) 458003..39 459046..23 550393..34 sSDD ((DDAAYY 111177)) -- 3 -- `Company Sanitized. Doesnotcontain TSCACBI 325231: One-Generation Reproduction Study in Rats DuPont9763 --~ APPENDIX C INDIVIDUAL BODY WEIGHT GAINS OF P; MALE RATS 150 Company Sanitized. DoesnotcontainTSCA CBI H-25231: OneGenerationReproduStcudtyiinRoants DuPont9763 r~ INDIVIDUAL BODY WEIGHT GAINS OF P; MALE RATS EXPLANATORY NOTES Notes TestDays 175 = Premating period Test Days 76:90 = Cohabitation period Abbreviations AK = Accidentally Killed FD = Found dead SD SE = = SSaaccrriiffiicceedd ibnyedxetsriegmnis; data excluded from group means. (Group 10, Animal No. 657409) - = NoDaa --~ --~ 51 -- `Company Sanitized. Does not contain TSCA CB 'H25231: One-Generation Reproduction Study inRats DuPont:9763 --~ INDIVIDUAL BODY WEIGHT GAINS (grams) OF P; MALE RATS GROUP: 1-0 DOSE: 0 MG/KG/DAY onDTAEYSST: ANIMAL NO. 665577339912 665577339930 665577339956 656577339987 665577349090 665577440012 665577440034 665577440065 665577440078 ~~ 665577440190 1-8 8-15 15-22 22-29 29-36 36-43 43-50 5447..32 4408.79 4460.44 a3l2l.o1 21260.39 2153.32 2249.089 s57e.l7s 4s2e.o7 3555..23 2268.183 316986 1200.32 330678 4392..19 430s0 447s.0 2274.133 22781s3 2291.74 2224079 aas2d 2a73.1 3381s 12371.77 3l2e2 225033 31114 aSo2s 4363s3 a3129 3276178 221113 116926 21230s8 33720087 3377..56 3355..96 3353..04 2235.83 118838 22550076 a58l0s7 wsa14 msa7e m392.9 3n6s6 204s0 1297008 aS611 seenlos 4346.25 330190 2376.07 2292028 2277.21 6a1l2a 4430.52 4225..78 3239..16 2278.36 11970.78 21680102 445107s a4s4i7a 4432.14 427258 119980 2214ls0 29074 --_ 5 Company Sanitized. Doos not contain TSCA CB H.25231: OneGeneration Reproduction Study in Rats DuPont9763 ~~ INDIVIDUAL BODY WEIGHT GAINS (grans) OF P, MALE RATS GROUP: 1-0 DOSE: 0 MG/KG/DAY onDTAEYSST: ANDIAL NO. 665577339912 665577339930 665577339956 665577339978 665577349090 665577440021 665577440034 665577440056 665577440078 ~ 665577440190 50-57 57-64 64-71 71-78 78-85 85-92 92-99 20123 115h2 23581-7 18 1228.30 1l4o.l6s 1107..84 281s 1176s6 74.s4 C-a77 1 123 116s6 1943s 1270.s5 22000068 112030 -226023 2158.30 1s8lso 2114l80 12011010 19658 150006-1-4731 2122..44 316s5 110501s1 113l0o as 21s1l0e les a63 12.7 9sl8o als 1811.37 18s 6888 2103 2190.81 17 15555 1103030 11030s7 6211 1s8n7 laelao a516 21098 1187101 229.44 aail1s 1s0l0s2 22a0l03s 11327 2172 2a031 1106d7 15s1 2o6l5s a1l1s1 118a2 3s1l8o se 1(D1A6Y 60) s- s s-lo 17-.9 12.02 2z 3 2s 8.1 s2 -47 12.8 142 7.1 --~ 5 `CompanySanilized.Doesnotcontain TSCACBI F-25231: OneGeneration Reproduction StudyinRats DuPont:9763 --~ INDIVIDUAL BODY WEIGHT GAINS (grams) OF P, MALE RATS GRovP: 1-0 DOSE: 0 MG/KG/DAY onDTAEYSST: 99-106 106-113 1-71 1-113 ANIMAL NO. 663577339921 665577339934 656757339956 665577339978 665577430909 665577440012 665577440030 665577440056 665577440078 ~ 665577440190 117.11 86.23 226993.011 3352200.21 1 13s 2938 23331.74 333900a8 1a51 182l000 225850.74 333052026 81ss a5n1s 129923003 2a1s9k6s 11s0 125.21 226s6s.l18 3219050s0 1437 1304 2250074 320867157 11883 21102 23266384 2g0e5l6d 150020 1all2s asllss aae0sell2s 5s3ls - 1a62s - 2320.a4 - 3257524097 5.4 32 2825 2841 -- 50 `Company Sanitized. Does notcontain TSCA CBI F-25231: One-Generation ReproductionStudyinRats DuPont9763 --~ INDIVIDUAL BODY WEIGHT GAINS (grams) OF P, MALE RATS GROUP: 111-0 DOSE: 75 MG/KG/DAY onDTAEYSST: ANDHAL NO. 665577441167 665577441189 656577442201 656757442232 665577442254 665577442276 665577442298 665577443310 656577443332 ~ 665577453956 1-8 8-15 15-22 22-20 29-35 36-43 43-50 aal1s 32980a7 3314.24 236853 212393 2103as 2126.38 33a6l.s0 3467..19 3338..90 3320.a4 330007 214122 220411 33913 3se6s0 333..81 3a077 23020007 313631 112d2 3a108 338972 2a5z.z4 230018 s 3172.1 2la3l4a 222023 a57l.s6 5656..56 4517..92 34106s 2308.06 2a9llss 2d1a9s 3aa7l0 4457..34 3303.50 330672 2354.36 22016 2270.14 a6s.e1 4s1a0s 2s2e3z a397.9 2308.02 118522 1295016 Sdo9d5 4553..94 4a2l6s 3a9s3a 3356..36 e24l.s0 1291032 6S10.91 5533..03 a4d3s 437375 3266.38 22950.00 3232037 2330027 321287 228a.7 12s9l85 211s:02 1s4a3 21260l5a --~ 5 Company Sanitized. Does not contain TSCA CBI 25231: OneGeneration Reproduction Study inRats DuPon9763 --_ INDIVIDUAL BODY WEIGHT GAINS (grams) OF P, MALE RATS GROUP: ITI-0 DOSE: 75 MG/KG/DAY onaTvEsST: 50-57 57-64 64-71 71-78 78-85 85-92 92-99 ANTAL NO. 665577441176 665577441189 665577442210 665577442223 665577442245 665577442267 665577442289 665577443301 665577443323 ~ 665577453956 19.s4 116592 112.68 6--1207.0 1105.73 114d4 251.15 1002 12s7 179s 1-9sl4a 5576 a5l2s 1i3e0s5 25082 226.161 130.a8 0a25 250.09 1s2l1a -136lss 11816 27681 2131015-130156 2200089 1115123 15495 1288081 211.30 2126.51 1-370.017 1171.69 1260.089 210114 0627 11435 95007 -0l7s 2105030 1s6o3 111430 82883 221275 1027 5-6276 8sl2s 116lso 21362a 112ss 2220.041 21050.27 56134 5a1s2 i5s8 153.04 21990047 2230l086 2106151 51.50-3s3la 2i0l0a6 32300s 8552 1903s 90.72-3017 s7l2s 05.64 155112 ~~ 156 `Company Sanitized. Does not contain TSCA CBI H-25231:One-Generation Reproduction Study inRats DuPont-9763 ~~ INDIVIDUAL BODY WEIGHT GAINS (grams) OF Py MALE RATS GROUP: TII-0 DOSE: 75 MG/KG/DAY onDTaesst: 99-106 106-113 1-71 1-113 ANDIAL NO. 656577441167 656577441189 665577442201 665577442223 665577442245 665577442267 665577042289 656577443301 656577443332 ~ 656577549365 130.73 126l2i 2a3m.i0z 227910.s7 r1t7 3830 222800122 23828835 102 18allso 228286127 327325.131 was2 1121l3s a2m0i0lsy 325666.144 E23X0s 0855 3a0l6l2 73088.24 17.4 0054 224179.21 239366.70 72..18 21s1ls7 236a09lla8 341207122 2w6.o7 1-22l.28 331276.11 3375680.08 116B0 9015 1m2ilo9 4355m3 12s.0 10s0l5s 119671.35 219573.28 --_ 7 `Company Sanitized. Doesnotcontain TSCACB) 25231:OGneeneration Reproduction Study in Rats DuPon9763 -- INDIVIDUAL BODY WEIGHT GAINS (grams) OF Py MALE RATS GroUR: V-0 DOSE: 500 MG/KG/DAY oNoTaEvSsT: ANIMAL NO. 656577444421 656577444403 665577444456 665577444487 665577444590 665577405512 665577445534 665577445365 665577445587 ~ 665577445690 1-8 8-15 15-22 2229 29-36 36-43 43-50 a29081 3330.03 4232.:03 218759 312132 1a5.18 1i9s.s9 448678 a4sse; 249310 324871 3as0l1e 2290070 133525 439300s0 432322 323076 319086 2198s0 2l1a2s 11833 3398070 336388 2323033 3al1as 3206s3 2159s0 2138 542a77 asi7s asalvs a29l0s1 125403s 195057 12418 a907a sa2sl?7 3476s7 a37l0s7 32443s 320413 118s1 3477.048 a44l9s 2368.28 2301027 2361l2s 3231033 da5.z4 2270.027 3531153 1m8.18 216103 2177..25 125644 179..75 4325..25 e41s3 s4uz4 4357.59 a2170 2224082 2183007 3310016 33290.89 2358..76 2s1l6s 229l79 210s08 1120s0 ~~ 58 `Company Sanitized. Does not contain TSCA CBI H-25231:OneGenerationReproduction Study inRats DuPont9763 INDIVIDUAL BODY WEIGHT GAINS (grams) OF P, MALE RATS GROUP: U-0 DOSE: 500 MG/KG/DAY onaTvEsST: 50-57 57-64 64-71 71-78 78-85 85-92 92-99 ANIMAL NO. 665577444412 665577444430 665577444456 665577444478 665577444590 656577405512 665577445543 665577445556 665577445578 ~ 665577445690 6a8s 112971 11a.l8o -11331.38 145.78 3s8s 0[X 3l3.s1 2520.06 1-71.32 23680 22986 110a0 1113s3 15298 47.78 1isi0s 05--162l34-156.0 158.30 13138 1159.38 17477 112666--0653 1528 150.68 76%5 s29o 113557 118331 csllsa 11533 5555 1s0l9o 02323 11633 28103 133s9 12726-31017s 3876 322.065 2125.52 1174.55 i-al4s s10l07 1E4X3 9998 1w2ss aas9s 1220. 8-1274 8i17 916 55.11 18317 1155.26 117.67 7-8709 a8s0s 1[2x3] 2s0a1 173.s7 a5l7s 117.66 7--3as1ls 2361l1e Ax 1(D1AY 86) 13-.1 -- 5 `Company Saniized. Does not contain TSCA CBI H25231:One Generation ReproductionSwdyinRas DuPow9763 -- INDIVIDUAL BODY WEIGHT GAINS (grams) OF , MALE RATS Grove: v-0 DOSE: 500 MG/KG/DAY onDmavess: 59-106 106-113 171 1-113 ano vo. ss8757a4a612 sess774a4d3s S885557740444576 865577444458 663377445510 663577445523 866533777444555456 885577445578 857459 ~~ 657460 269 7s.z5 1255.092 216648.38 1S6576 Sh o2l3s3 23103 2397%4 Bs aes 2mals 6@0 asi7z 1221 220828s m8l7s s1isa 2a6l00o3 2293m35 12502s 110as 225262s 23864255 1W017102 S70 ae zmaa3z 328090s7 mn NW06o a74m mselles 2a2m0o2 w13e7 = 7Coa 3a3l8s3 oes a2206 13.7 6.3 229.0 250.9 --_ iw Company Sanitized. Does nol contain TSCA CB H-25231: OneGeneration Reproduction StudyinRats DuPon9763 --~ INDIVIDUAL BODY WEIGHT GAINS (grams) OF Py MALE RATS GROUP: VIZ-0 DOSE: 3500 MG/XG/DAY oNaTvEsST: ANDIAL NO. 665577446667 663577446689 665577447710 665577447732 665577447750 665577447776 665577447789 656757448801 656577448832 ~ 656577448845 1-8 8-15 15-22 22-20 29-36 36-43 43-50 154..20 a28605 4254.67 1167..97 1169..38 3-03.14 2195.07 2205058 0253.5 260.13 a17l.s6 a30l.s3 213.77 8-92489 232s0 25832 2220.52 114s8 m13300 31s3-0063.9 3a0l0e 4209127 33018 3a177 1l2a1 1226143 121651 a2a5l62 218153s 21970.67 216324 210076 2-61478 52..56 44627 2a512 a-asll4 33620079 a5l.s0 AK a(DlAsY 42) 1-9a 4173'0s7 2s.i6z 3390.00 3230.93 278.a7 i19s0ss 235.91 3a07 4s3o8i 42s5..08 2396037 2a6l0i 123l2s 2a6l2s 2470.21 3se8l5s 2291.63 2310s1 7alss 0s0lgs aElXs] 2452.74 220881 4390.s6 31820l03 205o6ls 25s1s7 20321 -- Tol `Company Sanilized. Does not contain TSCA CBI F-25231:OneGeneration Reproduction Study inRats DuPon9763 INDIVIDUAL BODY WEIGHT GAINS (grams) OF P, MALE RATS Grove: VIT-0 DOSE: 3500 MG/KG/DAY oNDTAEYSST: 50-57 57-64 64-71 71-78 78-85 85-92 92-99 ANDHAL NO. 656577446676 656577446689 665577447701 665577447723 665577447785 665577447776 665577447798 656577448801 656577448832 ~ 665577448805 215.76 3217 16605--13629 1341.32 30.86 196.05s 220005 1157.95 20s0l9s 413s.1 222110-11670-61221.1 110253-1206.67 1sl4s 3-s9el1s 22728s 2l8oso -137043 1u5s0 26312 0 1o3zs 1-4al9z 2s7s l10o02-110263 1s90e2 258.74 13o1s1 6al3e oollss -oa2sli3s 7l8o v-s 12a 1: 5 2208 pi ls 2203-1220 1203.81 6377 120.16 73.19 1195078 1wa4l 6-576.8 129.078 12060.70 1244.31 10527-11is8is 1218a 1101 119052 2250.38 >43(.A6Y 66) -6.1 2-08 13-.3 -6.8 11907 36.55 -6707 12olae -u11l13 -01082 143s3 --~ 6 `Company Sanitized. Doesnotcontain TSCACBI 25231: OneGeneration ReproductionSwdyinRats DuPont9763 ~ INDIVIDUAL BODY WEIGHT GAINS (grams) OF P, MALE RATS Rove: VII-0 DOSE: 3500 MG/KG/DAY oxoaTEvSsT: 99-106 106-113 1-71 1-113 Anos wo. es5ss774aa668s7 665577447609 6s577a47712 656577447734 665377447758 663377447778 636737447890 e6s377a4s812 663377048834 --_ 637485 2S290301-125c72a 2mo3la 14 2a037.8 17500 Ja2n6 Tsazls allass 210704090 "Gl2o 7el7s 216k 2l02e.4 adlswn13 137 ez 2d0e2s els 1i9m7.i8 1676 3: 0 20<00 le:as 1828 2S.290 1B3.h5 2D2.r2 3i2s8.s8 S2lZss 2a7zl20 1s2ss7 a1l7` s6 024 20721 m1963.7 22140556 13s 1s 176 22803 PN -- ws Company Sanitized. Doss not contain TSCA CBI H-25231: One-Generation Reproduction Study in Rats -- DuPont9763 --~ APPENDIX D INDIVIDUAL BODY WEIGHTS OF P; FEMALE RATS DURING PREMATING --_ Tex `Company Sanitizod. Does not contain TSCA CBI H25231:OnGeeneration Reproduction Study in Rats DuPon9763 ~ INDIVIDUAL BODY WEIGHTS OF P; FEMALE RATS DURING PREMATING EXPLANATORY NOTES Notes TestDays 175 = Premating period Test Days 76:90 = Cohabitation period ~~ -- 6s -- - `Company Sanitized. Doos not contain TSCACB H25231: OnGeeneration Reproduction Study in Rats DuPon9763 ~ INDIVIDUAL B0DY WEIGHTS (grams) OF P, FEMALE RATS DURING PREATING GROUP: TI-0 DOSE: 0 MG/KG/DAY oNDTAeYsSt: 1 8 15 22 29 36 a3 ADL O. 657491 665577449532 665577449550 656577449976 665577449989 656577550010 665577350032 665577550045 665577550076 658577550088 --~ 657510 125097..10 12739a.l72 128607..07 129579.030 129772.195 231029..00 230071.048 118925..87 119967..48 222240.040 2233871.35 223472.174 224364.128 225a3d.l82 1198.464 2109070.35 22111315 2222170.60 2223010s2 222373.129 224321169 11983387 210s820006 211928..03 222308056 224378.58 223556..80 223566..49 2119a007 221271.l7s 2232980126 22540s1l86 2255831.39 227625..47 228721..46 l1s8e0l12 115729.015 210866..62 221072.161 2202090.28 221332..70 223149.041 129078.188 221086..29 223348..75 224591.70 2256661.08 2267831.17 229718..44 117984.169 125208.137 220388.51 2225451.33 226222..84 222721030 2237940113 119975..33 221181..19 223303..36 224500..13 2286587..41 2276381197 226788.160 118872.50 118878..35 21096..61 221128188 222198..71 223122..05 222354158 --_ 3 Company Sanitized.Doowessnotcont!ain TSCARCiBI F-25231: One-Generation ReprodSutucdytiinRoatns DuPon9763 ~ INDIVIDUAL BODY WEIGHTS (grams) OF P, FEVALE RATS DURING PREVATING GROUP: 11-0 DOSE: 0 MG/KG/DAY oNDTaEvSsT: 50 5 6a n ANIMAL NO. 665577449921 665577449934 665577449956 665577449578 665577455090 665577550021 665577550003 665577550056 665577550087 ~ 656577551009 2201891.20 2282500.25 3212080.37 321321043 2256230149 225741..77 2258301060 225890..48 225505020 22550083 2254671.34 225572.002 2256360035 227520008 2267000.83 2257160.20 s28e7l0s1 229002020 2298s7l.98 3209300.72 223a320l85 2200260.41 220081l.07 2245161177 2380821197 320966.015 02915189 321948113 2280040118 2295000057 2294571.84 224974.80 2288060028 228975.67 2298891.73 228976.101 224245177 2235030067 2225821194 222690091 --~ -- rer ----[-- pepr e em p ai Company Sanitized. Does not contain TSCA CBI B2S 523%:Onu e Gorerstn ion Reproducd tion yioRs DuP_ ou 9763 ~ INDIVIDUAL BODY WEIGHTS (grams) OF P; FEMALE RATS DURING PREMATING GROUP: 1V-0 DOSE: 75 MG/KG/DAY onoaTExSsT: Ann vo. ss8757551167 e35755115 6e3577552201 66377552223 86655777555222564 8s5s7552287 885577553209 esss77553312 6E337755333 ~~ 657535 1 8 15 2 29 36 11766.128 28020.s4 2159.937 22134..53 22325..29 225218..29 225313..07 119972.41 22003501 2275.26 224269.53 220692.75 228635..22 228882.11 l1o9s8i0s4 211s4773 2a3l1r1 2a00l00 223481.25 220467.73 225631.09 lIsellaa 20800 8271565006 22225.s1 aaa 228:671 298 22457015 2773 22406.82 2e14 226533.90 2923 1T9e4s010 2z0o0117 22a2m.l4o a23m6.s5 22430.00 225555.51 228334.91 110930005 2702a4)7 22a116l.68 22255..26 222880.64 228491.23 225908..90 1107780153 212s0a0s1 2230671.90 2201670.38 223508..45 223632..09 221431..36 I20s1l0s4 220180.s0 2222970.76 223542.35 226551.65 226617..41 226654..40 TTessli9s 220002000 2222000058 22316..82 225347..26 225668..40 226723..23 198.6 214.4 234.8 256.7 263.0 272.7 280.5 a-- Company Saniized. Doss not contain TSCA CB H-25231: One-Generation Reproduction Sudy in Rats Dupont9763 ~~ INDIVIDUAL BODY WEIGHTS (grams) OF P, FEMALE RATS DURING PREMATING Grove: 1v-0 DOSE: 75 MG/KG/DAY onaTvEsST: Anz wo. 665577551167 665577551189 665577552201 656577552232 656577552245 656577552267 665577552289 665577553301 656577553332 ~ 658755735530 s0 5 6a n 225d50..00 225457..10 228638..36 227427.28 227003050 231172.197 232759..38 2380031171 2256860.10 225788..97 227707..61 227865.67 227543..37 226139..98 227762..51 227071799 229658.151 320656..54 327231188 3208621051 2255750050 2265361137 226663.48 2277191.63 2200967086 32008311s5 235168143 3215760.60 228711.04s 22075m1.68 2298131.30 320844l.66 2287030152 2280961187 22961..10 228864.s0 2288050.63 2278151.s5 2299301.35 229987..80 -- 16 Company Sanitized. Does not contain TSCA CBX $5:25231: One.GenerationReproduction Study inRats DuPont9763 ~ INDIVIDUAL BODY WEIGHTS (grams) OF P FEMALE RATS DURING _ Grove: VI-0 DOSE: 500 MG/KG/DAY oxDrAeYsSt: 1 8 15 2 29 ANTAL NO. 656577554021 665577554434 665577554456 665577530487 6655775545809 665577555521 665577555503 665577555556 656577555587 ~~ 665577556509 119936..13 220075..70 222169..18 223833..80 2253561.61 21191283 211339.031 223184.25 226237..05 226491.50 210863.020 211911..75 221059..30 222381..31 222289.103 2f0e0s0.14 213921..42 215945..65 226171.94 226294..50 16885.030 210802..44 212859..40 214915..23 224076.183 21093683 221054..30 22029078.3 225233..70 225365..48 lie7s32 119871010 211932.34 221058.76 2220471.10 219134.34 223065..27 225076..49 226339..34 227472.14 11985433 210899..47 221260..85 223320..80 2243581174 210525..06 221311..10 221543..47 223892..89 234085..02 PREMATING 36 a 225444..15 226435..44 227856.149 22573174.2 223454.107 223465..85 226298..87 222733..80 221556..38 225132..64 226338..13 22732..58 2232301.51 222471.83 2284091024 228435..29 224551.43 2255260.79 228550..35 234120.096 --~ _-- 0 Company Sanitiyzed. Does not conje:n TSCACBU H25231:OneGeneration Reproduction Study inRats DuPont9763 ~ INDIVIDUAL BODY WEIGHTS (grams) OF P, FEMALE RATS DURING PREMATING GROUP: VI-0 DOSE: 500 MG/KG/DAY onDTAEYSST: 50 57 6 n ANTHAL NO. 665577554412 665577554413 665577554456 665577554478 665577554590 656577555521 665577555534 665577555556 665577555578 ~ 665577555690 225767..76 225882..96 225876..30 229655..70 2250221038 2270920103 227977..24 231840.84 226449.008 2255861.18 226649..46 226655..89 23300095 23412687 2342870.74 324451.75 a26u0.s9 a26s7.s1 222776..85 2227671.26 228500..11 2258481037 225981..73 229555154 2230910.70 2203271.70 225455.105 225555150 226023.87 2360050.48 236091.00 230648121 225669..55 227509..96 226671.87 226799.92 321589.035 326356.s8 236266.72 3226030.84 -- i Company Sanitized. Doesnotcontain TSCA CBI H25231:OnGeeneration Reproduction Study in Rats DuPont9763 ~ INDIVIDUAL BODY WEIGHTS (grams) OF P; FEMALE RATS DURING BRENATING GROUP: VIII-0 DOSE: 3500 MG/KG/DAY oNDTAEYSST: 1 5 15 22 28 36 4) ANIHAL NO 665577556676 656577556689 665577557710 665577557723 665577557745 665577557767 665577557789 665577558810 665577550823 ~~ 665577558850 118857..52 218174.59 223020..89 224273..71 226327..60 224654..99 227042..34 1179960.87 119s7a.06 220281..28 223130.71 223414..02 224255.119 224267..60 1185087 12070068.7 211961.073 2212520109 222470..05 222415..22 22143127.6 2s0a81l7 12s1e3l027 220323071 2214071.43 226261115 2236070.08 2227810.76 119984029 212979..94 223114..55 228209..92 223630..69 225534..67 225575..72 2117070.73 21287s..2 214540..74 225003..58 225174..31 222587..72 227202..30 11991312 117995..40 221162..77 222281.78 228204.133 224358..81 224381..47 1270801025 125102.010 2204040.90 2240790.24 2205960.05 221627..12 221663..81 210888159 121852074 223116.089 223455..48 224552.138 224507..41 224676..22 2s0l8ls0 12e0e3l171 2203111010 220466026 22240a0l51 222624105 2228230.73 --~ Iz -- `Company Sanitized. Doesnotcontain TSCACBI 25231: One-Generation ReproductionStudyinRats DuPont9763 ~ INDIVIDUAL BODY WEIGHTS (grams) OF P; FEMALE RATS DURING PRENATING JGROuUPh: VITI-0 DOSE: 3500 MG/KG/DAY ---------- oNDTAeYsSt: 50 5 EA 7 ANDHAL, NO. 665577556667 665577556689 665577557701 656577557723 665577557745 665577557767 665577557789 656577558810 656577558823 ~ 665577558854 222508883...888 225869..95 261.6 225803..48 27113 228699..35 209.7 222550..11 22538.66 224628..79 224729..84 222797012 2355 228081159 205.3 222034056...420 229404..63 229.4 226073.26 228m8..02 22895.73 229972..78 227245..15 2283050.38 2274641118 227465..65 226415..33 226450.025 226561..79 227588..41 227253.038 228320..91 2283171.78 228480..91 220770.026 225770..45 225793..66 226833..97 223650..23 220703..52 224841.18 226319.26 -- J ia ----`Company Sanitized. Doesnotcontain TSCA CBI 25231: One-Generation Reproduction Study in Rats --~ DuPon-9763 --_ APPENDIX E INDIVIDUAL BODY WEIGHT GAINS OF P; FEMALE RATS DURING PREMATING e-------------- i 3 ---- errs Company Sanitized. Doss not contain TSCA CBI F-25231: OneGeneration Reproduction Study in Rats DuPont9763 ~ INDIVIDUAL BODY WEIGHT GAINS OF P; FEMALE RATS DURING PREMATING EXPLANATORY NOTES Notes TestDays 1-75 = Premating period Test Days 76:90 = Cohabitation period --~ --~ -- e-- r ---------- id -- Compan-- y Sanit-- ized.TDoS-- es not-- c-- onta-- in T-- SCe A CBI 25231: OneGeneration Reproduction StudyinRats DuPon9763 ~ INDIVIDUAL BODY WEIGHT GAINS (grams) OF P, FEMALE RATS DURING PREWATING -_ GROUP: TI-0 DOSE: 0 MG/KG/DAY onaTvEsST: 1-6 81s 15-22 22-20 29-36 36-43 43-50 ANIMAL NO. 665577449912 657433 2207.26 1 30.33 5-8177.3 23.6 1715 10.s6 02 3151-1062 8s 76 3116.6 1001 665577449954 657496 3271 31 1253.26 136 1133s9 10s aas1 alrle als ow oa9s.l47 a7 18223 1 665577449987 657499 18125 2.1 a5o7 2s 2226.53 116 179.39 31 <8122 18s o0lss 100 1966s a7 665577550010 657502 10s0l8s 1751 1w0l 11232201 xd 67 159 71 271.28 as 2sao 178153 5a 1407 665577550083 657505 2020.41 17 3166ls 1s 1107005 162 12138 -ils 15.19 -04 2a373 17d 1n05i5 57 665577550076 657508 T29e0s8 18 291.78 162 210687 9.8 17851 17.0 0ss3-0310 168 a1 15882 22 --~ 665577551009 afss w9z3 11622 7-01679 5213 12l35 3-010102 --_ S ------------e --eepeesees e 76 ma Company Sanized. Does not contain TSCA CBI B25231;One GenerationReproduction SudyinRats _ DuPont9763 ~~ INDIVIDUAL BODY WEIGHT GAINS (grams) OF P, FEVALE RATS DURING PREMATING eeeGRovP: 11-0 DOSE: e0eMGe/KG/mDAsYes oxomaarsst: so-57 S764 641 171 ana Yo. 66s55s777444999321 as3s 28 aas2l es 2207 17082333 os sso 656377449945 657496 S2s3 aalas 0s ss asllss sesls 07 7s 663577449987 637499 251 23 a aTaos sslis eerls ws asi 66377550010 67302 35320 ae asaa se 1a0h a3 7mlbs els 663377550034 637505 wS6i3 ao3e S533 n2l2s 11000s3 co esl 663363777555000768 180s4 25 6533 70 2a3 1a s9s7s sels ~ 63s77550209 Lsso 3 on eaols aTella --~ Id Company Saniized. Doas not contain TSCA CB F-25231: OneGenerationReproduction Study inRats DuPont9763 ~~ INDIVIDUAL BODY WEIGHT GAINS (grams) OF P, FEWALE RATS DURING PREWATING GROUP: TV-0 DOSE: 75 MG/KG/DAY onDTAEYSST: ANTAL NO. 665577551176 665577551198 656577552201 665577552232 665577552254 665577552276 665577552298 665577553310 665577553323 ~ 665577553354 1-8 8-15 15-22 22-29 29-36 36-43 43-50 26.42 11689s 147.166 52..54 1a573 0a.82 6a30 1s0l0o6 2104061 21111s 2106040 23s7 aalss n1l1ad 1u61r3 216al 1sslo i8l6a 67s7 17363 a520 228772s2 1s7s9 93 21a080 slo oaiss 11ls wa3l 7 a1 13818 nl 1000.74 31 67.61 221033 1648 Bl 127 58 38525 a1s8ls aollos 2s 128 5.7 a5s2 a1 3s2ls 2l2e2s 110686 21220046 2867 s817ls 5108 25275 a16l1y8 aosa 11720302 a988 2206s 7861 19s1 210100 1250373 113a2 118s6-1s7is l1so 1156518 21080l4s 231180 523a 15s7 75383 a73s -- _-- ig Company Sanitized. Does not contain TSCA CBI 25231: One-GenerationReproduction Study inRats DuPont9763 ~~ INDIVIDUAL BODY WEIGHT GAINS (grams) OF P; FEMALE RATS DURING PREMATING ROU: 1-0 DOSE: 75 MG/KG/DAY onDTAEYSST: 50-57 57-64 64-71 1-71 ANTAL NO. 665577551176 656577551189 665577552210 656577552223 665577552254 665577552276 665577552298 656577553301 665577553332 ~ 665577553351 70.10 16335 64..12 7806..86 1790.29 1121136 -22o.l2s 10e6s.l03 1o2s 7-11167 86s1 10708.30 156 3s7s 13.588 7905s 120.033 175.49-151833 9987.05 15.77 10011 18225 8778.36 -82.l77 12s.l4s 0ol3s 1727411 1062 2-41132 11363 180671.30 39:53 s1a2 cssl 9894060 90:12 2s1l 8 65155 19182..49 -- _-- I Company Sanitized. Doesnot contain TSCA CBI H25231: OneGenerationReproduction Study in Rats DuPont9763 ~~ INDIVIDUAL BODY WEIGHT GAINS (grams) OF P, FEMALE RATS DURING PREMATING GROUP: VI-0 DOSE: 500 G/KG/DAY a onaTvEsST: 1-8 8-15 15-22 22-29 29-36 36-43 43-50 ANTHAL NO. 665577550012 65577554434 665577554465 665577554487 665577555409 665577555521 656577555534 656577555556 665577355587 ~ 656577356509 w8s7 1184..48 116491 122.026 -51.s4 58 1s 133 140 5.4 90.93 2 113 65 ols 817s 218732 129435 i6.o0 15s.i4 513 38 iss 21 6.0 o1l8s ssllss 18 1300 222.83 2423 112068 122111 10 66 63 als 0a37 sai0z 2n6l0s7 sla -2ls Colo 17a.7 255508 1135.028 125168 als wl 2604 27 3sl1o l0z6 170.036 517 517 7.3 u7.s9 116s4 1210s2 1233 12 3205 2835 1olha 8732 o1l2s 27 73 al 1s 2sa 2a721 1350.29 1E0X1 way 1a 123 120 6250s8 a8l0o 15060 517 13 a2 325014 =33 229s2 2a223 l6s5-12863 176.67 --~ _ 3) `Company Sanilized. Does not contain TSCA CBI 1.25231: One-Generation Reproduction StuyinRats DuPon763 --_ INDIVIDUAL BODY WEIGHT GAINS (grams) OF P, FEWALE RATS DURING PREMATING -- a --------GR-- OUP:--VI--- 0 ----DO-- SE: -- 500 -- MG/K-- G/DA-- Y p ---- e--e -- onaTvEsST: 50-57 57-64 64-71 171 ANTAL NO. 665577550421 665577550043 665577554065 665577554487 665577535409 665577555512 665577555503 656577555556 656577555587 ~~ 656577555690 2sl2o 1364 97..77 16082.67 16524 lalss 137.60 10s2s.s6 -s7l09 1716s 317a see2l9s0 6729 10s0o7 1243 1731as 57..20 ol9a3-111 s5el1s 8a26 2a.s6 3121 nslesl 2177 12880 oollss 629313 5361 0362-0381 7ss4s 21107 3222 1271.2 7935s6 1623 9o8a 2sl8o 1e2l2a2 -- Pr res ---- SS---- rseep-- 1s Company SanDoiastnoticontzaineTSdCAC.BI H25231; One-Generation Reproduction Sudy in Rats DuPon9763 r INDIVIDUAL BODY WEIGHT GAINS (grams) OF P, FEMALE RATS DURING PREMATING Rove: VITI-0 DOSE: 3500 MG/KG/DAY onATvesst: ANDOAL NO 665577556676 665577556689 665577557710 656577557732 656577557758 665577557767 665577557789 656577558801 665577556632 ~~ 665577558854 1-8 815 15-22 22-29 29-36 36-43 43-50 2067 0s 118.30 242 114832 113 l13e.s9 1261.79 2228..54 11-13 11 56.s4 se 2a021 20 1250129 we 5225 237 21080030 120 14431 sls 21ss o11ss 7s 15s 1s4l1o 3307 230s a0 18236 slo 11090272 -713 a153 2000 1338 a1 5681 ss 1o6s5 115715 1578 1s7s o 1s-ooos 123.84 m31s als 2270 33 m1l2e1 50 n1l0s3 26 51E5s 627.6 138-4 1230s9 136 uusa 132s0 2334 092s 1030013 3aa0 172.07 lSollss fos 13624 2709 11480s0 5965 12-21 41a3l 5518 als -1007 a0l0a 7.0 ds sil ss 13 200 02 12s ~~ eeeeeeee Commpeaney Seant iized.e Dossne otcon tainTSCACBI H-25231: One.GenerationReproduction StudyinRats DuPont9763 -- INDIVIDUAL BODY WEIGHT GAINS (grams) OF P, FEMALE RATS DURING PREMATING GROUP: VITT-0 DOSE: 3500 MG/KG/DAY -- onaTvEsST: 50-57 57-64 64-71 1m ANIMAL NO. 665577556667 665577556698 665577557710 665577557732 665577557754 663577557776 656377557798 665577358810 656577538832 ~~ 656577558805 8s 1-s 65 1238s a5.17 1a2s3 61033 79.82 05175 -9aas 2257 16023 as2lo a375 n1ls 6731 a7.27 100012 32012 152179 3is] 18s.i1s 10832132 0814 e8l3o0 1901s 9s88l.s7 16062 4e5s3s 113118 29033s5 0075 eess2o 1672 867s3 7223 sslsso 1a031 7slsa s6slemsls --~ i `Company Sanilzed. Does not contain TSCA CBI F-25231: OneGeneration Reproduction Study in Rats --~ DuPon$763 APPENDIX F --~ INDIVIDUAL BODY WEIGHTS AND BODY WEIGHT GAINS OF P; FEMALE RATS DURING GESTATION --~ 5 -- -- `Company Sanitized. Does not contain TSCA CBI H.25231: One-Generaion Reproduction Study in Rats DuPont9763 ~~ INDIVIDUAL BODY WEIGHTS AND BODY WEIGHT GAINS OF Pi FEMALE RATS DURING GESTATION EXPLANATORY NOTES Abbreviations NP = Nolitter delivered; data excluded from statistical analysis. = NoData ~~ --~ - is -- -- Company Sanitized. Does not contain TSCA CBI FHL25231: OneGenerationReproductionStudyinRats DuPon.9763 --_ INDIVIDUAL BODY WEIGHTS DAUNRDINBGODGYESWTEAITGIHOTN GAINS OF P, FEMALE RATS GROVE: 11-0 DOSE: 0 MG/KG/DAY GESTATION DAYS: ANIMAL NO. kl 1 2 MEAN BODY WETGHT (grams) 665577449512 232033..11 325591.16 238985..28 439106..48 665577449943 226648..38 3300010.15 333368..31 442066..75 656577449956 (NP) 223640..71 227832.137 237175..33 238720.32 665577449987 2267980.06 3301201047 334361.48 410386.25 657499 657500 2208780087 333169.020 336376..20 44d163.122 665577550012 225485102 228943.040 3312831102 440055123 665577550043 3310231.34 33a3s475 3385091077 44s081.82 665577550065 2204181114 329301.06 334179.156 43196836 665577550078 2200871.12 33320833 335658.l0s 445368..76 --~ 656577551009 (Ne) 226376.167 226701..18 2287941.02 325578.49 GESTATION DAYS: ANIMAL NO. 07 74 wet on MEAN BODY WETGHT GAINS (grams) 665577445521 665577445943 656754784556 (Np) 665577449987 665577459090 657501 656577550032 656577550005 665577550076 656577550089 (vB) 657510 l36o.5 a287.6 s28a.s6 19837.37 335332 336626 se0sli2s 113681.74 125202 33356-71es0a 1i2s2i1s1 3336.14 232001 787s.l1a 115379.065 a27z05 2is8i2s e77l.o2 l1a2s4s5 3s9a.s4 3303:6 8s2l3s 118407i.30 333.14 325502 747215 1s4s5a9 239205 1268lss e73s0r1 112s5022 33612 420027 s83z6 1159a05 2a32a 292021 1e6s0i12 a8m1l77 --_ 3 `Company Sanitized. Does not contain TSCA CBI F-25231: OneGenerationReproduStcudtyiinRoants DuPont9763 --~ INDIVIDUAL BODY WEIGHTS DAUNRDINBGODGYESWTEAITGIHOTN GAINS OF P, FEMALE RATS GROVE: 1V-0 DOSE: 75 MG/KG/DAY GESTATION DAYS: ANIMAL NO. 0 7 12 MEAN BODY WEIGHT (grams) 665577551167 665577551189 (ve) 656577552210 665577552232 665577552245 657526 665577552278 6575292 6655775533102 665577553323 657534 --~-- E6S5T7535 GESTATION DAYS: ANIMAL NO. 226560.39 27-.7 226879.025 2287270.01 2361890004 227700.14 36ls 295-.1 226093005 263287071..501 07 MEAN 320893.083 334152.102 30930s 337-.2 239140.085 332397..15 3219381133 332101032 3259271051 33931353 3300307s 333203068 3a5l5 363.5 - - 328-.6 354-.8 2302770.11 334262.035 3311930.0055 M334686613s3 7-14 14-21 BODY WEIGHT GAINS 442079..07 ai-ls 349195..00 43033637 438999.31 34543933 451 413-.2 338998..11 M43397 1371 oz (grams! 665577551167 aa2l.o9 3285029 9826.87 116508..87 656577551189 (NP) 2-02 27-53 e-sl 16- 1 656577552210 227.06 320730 7697.s9 113218.58 665577552232 3211038 21620.04 2835041 1529063 665577552285 320201 338692 6970.6 116391.37 - 665577552267 2303034 2336111 10299l0s7 17m8029 657528 6575298 2807 . 18.0 - 8-78 13-4s 6565775533012 3-.5 2:62 s-ee = 118. 665577553332 3287..16 1259.24 4725s6 1926816 665577553345 33220.54 22620086 3s6s5a 1916s ~ pr -- aBvidence of copulation was not observed: therefore, no gestation data were collected 7 Company Saniized. Does not contain TSCACBI F-25231: OneGeneration ReproductionStudy inRats DuPon9763 --_ INDIVIDUAL B0DY WEIGHTS DAUNRDINBGODGYESWTEAITGIHOTN GAINS OF P; FEVALE RATS GROUP: VI-0 DOSE: 500 MG/KG/DAY GESTATION DAYS: ANDHAL NO. [3 712 MEAN BODY WEIGHT (grams 6565775540212 220750..16 231970..87 338251..28 422-.2 665577554438 3207900040 330423040 3372811.91 440474.99 665577554465 2266850.99 239003..12 3323831.46 441183.96 665577554487 328367..02 3261355s 3289571.71 344672..83 657589 6575500 22001 0 2659 - 293-.5 368-.3 6655775555215 203-.4 320-.1 339-.9 432-.4 665577555534 225515..18 2288290077 331202..60 346053..74 665577555565 321722.149 33130l0s3 337840130 441123.79 665577555587 (vB) 266-.1 282-.8 305-.3 376-.8 ~ 665577556509 237376.66..55 3371161.08 314021..-48 413640.61 GESTATION DAYS: ANIMAL NO. 0-7 74 121 on MEAN BODY WEIGHT GAINS (grams) 6655775544212 222.71 2271.14 77-.0 12-71 665577554443 332a000 31910s1 7s0ell0s 113375.59 665577554465 2372.23 337034 8essllso 115520.07 665577554487 1387.53 2212026 66s2.12 112051181 657549 6575500 368 - 276 - 7.48 13-92 6567575555210 26-.7 19-.8 92-.5 139-.0 , 656577555534 3304065 227.38 85501s7 111138.39 665577555565 337.a0 33002 9729l76 i1e0s0 656577555587 (NP) 16-.7 2-.5 71-.5 110-.7 665577556509 430053 3251040 Sse1l7s 11527.16 --_ 3 ABmviindaelncdeeloifvecroepudlaptriioonr wtaoscnooltleocbtsieornveodf;Getshtearteifoorne,Dayno21gedsattaat.ion data were collected. e eee rie Company Saniizod.s Does not contain TSCA CBI H25231: OneGeneration Reproduction StudyinRats Dupont5763 -- INDIVIDUAL BODY WEIGHTS DAUNRDINBGODGYESWTEAITGIHOTN GAINS OF , FEMALE RATS Grove: vIrr-0 DOSE: 3500 MG/KG/DAY esTATION DAYS: ANIMAL Yo. ?12 MER BODY WEIGHT (grams) 6a7s5s6e7s am) 857368 327-.6 338-.9 3002.6 325.9 2758 dela 3315 41605 8G5s77557609 wm) a2507.0 e28l00a0 23739033 24252966 ss8757s577128 090.3 as. 30:7 42007 885577557743 22953.05 32es3iz 33260d3 433804ss 875775576 we 857577 23001>3 331166s7 s3e1l4s9 43550050 sala 276s 308 376.7 8755757769 (wy 657580 7 211.6 Ze a2m1e8s7 320s 3219106 s dans 327538065 430s G85577556821 aw) 657563 226487.78 22924..44 237004001 238806..86 Zoals a3 387 40807 --_ ss5s77538854 2es6ii5s 236070.s8 232a033a82201 GESTATION DAYS: 07 714 wen oz AL No. MEAN BODYWEIGHTG-AINS(grams) ss55s7e56e7a (vp) 857568 q.a 1- 7 omR a - 7 3 227 eso 1400 87537567s0 am) 03900-0ae1s 280933 109069 ess7s7s577i2a 857573 6..4 22-.0 8-.0 Dl- a Bo ma saa ial G6377557754 aw) 637578 135a4 m118 11015 a24s2 30 300s sal 1690 + 685577587778 (vp) 857579 3371 alo mass 27l0 0ml1s 12370ss a0 1020 s8s577550810 S782 am) 22073 amlisa 256-243 ssellss 113386.39 1007 12.0 63673755883 85738 IBoe mmlas emiso 1133207 05 le esl7 sls --_ e @ Brioideecncte eedof copue lation wes not observed; therefore, no gestation data were is `Company Sanitized. Doss not contain TSCA CBI F-25231: OneGeneration Reproduction Study inRats --~ DuPon9763 -- APPENDIX G INDIVIDUAL BODY WEIGHTS AND BODY WEIGHT GAINS OF P; FEMALE RATS DURING LACTATION --~ 50 - -- Company Sanitized. Does not contain TSCA CBI 25231: OneGeneration Reproduction Stdy in Rts DuPont9763 --~ INDIVIDUAL BODY WEIGHTSDUARNIDNBGOLDAYCTWAETIIGOHNT GAINS OF P FEMALE RATS EXPLANATORY NOTES Note Test days for animal fates are determined from the initiation of test substance administration. Abbreviations -= NP = SD = NoDam Notpregnant Sacrificed by design PN ~~ et ior eee e Company Sanitized. Does not contain TSCA CBI H25231: One GenerationReproductionStodyinRats __ DuPonc976s ~~ INDIVIDUAL BODY WEIGHTS DAUNRDINBGODLYACWTEAITGIHOTN GAINS OF P, FEMALE RATS Grove: 11-0 DOSE: 0 MG/KG/DAY LoacvTA:TION " po 2 AHL wo, MEAN BODY WEIGHT (grams) es6577a49s2a 237682..71 2307360.76 33091.54 381-.6 SSDD ((DoAAYY 112211)) 65es77449943a aal6s 33231131 33468190 317-.1 s5DD ((oDAAYY 112213)) 565577443956 (ue) 657497 298-08 309.3 320-07 335.2 330-.6 348.0 3157.6 SsDo ((DoAmYy 112230)) 326.1 5D (DAY 12) 685577445989 857500 330100013 310s 330316.76 leas 332020.24 368.0 330312.165 55DD ((DoAAYY 112232)) 356.0 5D (DAY 122) 565577550021 657503 330000.013 326070.i7 331121.31 333160..71 55DD ((DDAAYY 112230)) 32805 3417 358.0 330.6 SD (DAY 122) 685577550085 33589l0s4 338156.81 3337960.31 335224..60 S5DD ((DDAAYY 112223)) 665577350067 557508 3342631039 35305 335a1l.l6e 33:le 3337652730..768 335374..96 5SDD ((DDAAYY 112232)) 354.0 5D (DAY 121) -- 885377530190 (we) 262-.7 296>.7 317-.3 286Z.7ap5D ((DoAaY 112246)) LACATvAsT:ION 07 714 wen oz aL No. MEAN BODY WEIGHT GAINS (grams) s85s7r4a5s21a 17l96 2u0s8 12.9 19=.5 s5pD ((ooaAvY 112211)) s8s577a4s538a 238s2 m18ss 0.9 12=.2 s5p0 ((oAaYy 112213)) 865577449956 (v9) 2-s o-ls sl- o l=eis sspo ((ooaavY 112230)) 658577449987 251.39 1220.88 2210.098 161..83 SSDD ((DDAAYY 112238)) 685577459090 857500 205706 07 o3l5s 181 e7l.o7 17.8 24141-5s0 ((aayy 112222)) 36.6 SD (DAY 123) 885577350023 s1i3z1e 218643 2270.40 29.80 5SDD ((DoAYY 112202)) 555577550058 857506 2B5l0o7 S53 -m9l.s0 2C13553 Teo 907 -56..28 55D0 ((DoAaYy 112223)) 111s sp (oa 123) 885577550087 G117037 10212 -8is7lz 1100.715S0D ((oaav 112221)) 657509 (up) - - = = so (oa 120) --_ a tactation day 21 body weight inadvertently not recorded. 2 `Company Sanitized. Does not contain TSCA CBI H-25231: OneGeneration ReproductionStudy iRats DuPont9763 --~ 657510 32.0 22.6 30.6 24.0 SD (DAY 126) --_ -- 193 -- `Company Sanitized. Does not contain TSCA CBI F-25231: One.Generation Reproduction StudyinRats DuPon9763 --~ INDIVIDUAL BODY WEIGHTS DAUNRDINBGODLYACWTEAITGIHOTN GAINS OF P; FEMALE RATS Grove: 1V-0 DOSE: 75 MG/KG/DAY LACaTvAsT:ION o 712 ANIMAL NO. MEAN BODY WETGHT (grams! 665577551176 657518 231980..35 321958..22 333281..24 330208..07 SSDD ((DDAAYY 112230)) 31004 326.7 380.1 322.6 SD (DAY 122) 656577552109 (vB) 288-.4 325-.2 330-.0 323=.4 s5pD ((DaAyY 112214)) 665577552221 657523 333313.085 334341..38 331326..48 334380..45 SSDD ((DDAAYY 112233)) 290.9 3126 316.9 323.4 5D (DAY 123) 665577552245 2295300.64 333709..76 335839..02 332618..89 SSDD ((DDAAYY 112215)) 665577552276 332024137 3333900.89 335411..54 333431..01 SSDD ((DDAAYY 112202)) 665577552289 657530 238405..08 330858.103 331376..71 330521..76 SSDD ((DDAAYY 112221)) 309.7 327.3 347.3 355.3 SD (DAY 123) 665577553321 657533 3321900s6 334538..13 335648..66 334431..34 SSDD ((DDAAYY 112237)) 289.2 303.5 328.6 296.1 SD (DAY 121) ~ 665577553345 334205..54 334332..38 335556..18 334432..43 SSDD ((DDAAYY 112235)) LACaTvAsT:ION 07 74 wen on ANIMAL NO. MEAN BODY WEIGHT GRINS (grams) 665577551167 656577551189 (ve) 665577552210 665577552232 665577552205 665577552276 656577552298 665577553310 665577553332 665577553354 37..16 2233.02-291.45 1-63 1-308-171- 5 3a16.8 5a08 66.36 2I27ls 314.39 366..05 3879.21 292.35 3210132 1276.025 110156-181-05.3 252.005-12102.27 -1155.005 218067 2100003-27520 12133 215115-13121038 27%4 120s00 l18yls 109..44 SSDD ((DDAAYY 112230)) 12=02 SsDp ((oDAAYY 112202)) 35-.30.080 ((boAYY 112231)) 3126..56 SSDD ((DDAAYY 112233)) 2788.25 SsDD ((DDAAYY 112215)) 1306..38 SSDD ((PDAAYY 112202)) 225..73 SSDD ((DDAAYY 112221)) 1415..86 SsDD ((DDAAYY 112273)) 2150.59 SSDD ((bDAAYY 112213)) 126.35 SsDD ((DDAAYY 112235)) -- 4 Company Sanitized. Does not contain TSCA CBI H25231: One Generation ReproductionStudyinRats __ DuPont9763 -- INDIVIDUAL BODY WEIGHTS DAUNRDINBGODLYACWTEAITGIHOTN GAINS OF P, FEMALE RATS Grove: v1-0 DOSE: 500 MG/KG/DAY LacDTaasT:ION 0 ? 14 2 ANAL No. MEAN BODY WEIGHT (grams as6737550412 637543 3320250.s4 20816 33068.70 31905 331473.i9 331.3 332179..20 5SDD ((DDAAYY 112222)) 312.8 5D (DAY 121) 656673577555444554 637547 303041690.562 32370046.78 333534315...565 333220688...170 55SDDD (((DDDAAAYYY 111222203))) 2202 283.6 305.5 291.7 SD (DAY 123) 638577554489 857550 23708.171 Sorz 237888.s9 a1 330789..12 380d 335091.71 55DD ((DDAAYY 112218)) 31019 sD (DAY 125) ss8757355521 857553 S804387 las JBaIo zie 3334070.45 3313 3315611.16 55DD ((bDAAYY 112220)) 317.4 5D (DAY 123) 885577555545 5207641s1 332064.70 335203.068 332096..16 55DD ((DDAAYY 112231)) 853577555567 (vp) 857558 330885-..96 330623-..58 333815-..95 378=".6 s5pD ((DAAYY 112241)) 314.4 5D (DAY 121) 857559 37.5 384.3 40815 378.3 5D (DAY 130) ~~ 657560 319.9 326.5 352.4 343.6 SD (DAY 122) LaDcATYAST:ION 07 7-4 wea 021 NAL No. MEAN BODY WEIGHT GAINS (grams) 65ss77554021 657543 1 S14 217.19 e1s1 143.465s0 o(AaY 112222)) 2005 nila C185 182 sp (oAY 123) 656757554458 857548 22061 7mlas ealsss 4217.22 5spp ((0avA 112203)) 15 26s -5ls 19150 (oAY 122) 885577554487 857349 a1las 2Clols3 2-0;ll1s 2190165 sspp ((bbaayy 112283)) 17 1903 ela 27. sp (day 121) - 865577555510 57552 2339025 168043-134.53 31133.7 5D ((ooAYY 112225)) 56 a6z a1 19s (omy 128) 658577555534 857555 2730s9 198017-1137.92 321.168 5S0D ((DDAAYY 112213)) Ils 2als als 23.0 50 (DAY 123) 665577555576 (ve) 657558 1=37 i-sa 7-3 22="08 s5o ((oaaxy 112201)) 2a 2a 17.5 9.550 (DAY 121) 656577556509 67as 2305s 5-a868 2-32.l7s 5spp ((DoAaYv 112320)) --~ 95 Company Sanitized. Doss not contain ICA CBI F-25231: One.Generation Reproduction Study in Rats DuPont9763 --_ INDIVIDUAL BODY WEIGHTS DAUNRDINBGODLYACWTEAITGIHOTN GAINS OF P, FEMALE RATS GROUP: VIII-0 DOSE: 3500 MG/KG/DAY LACaTvAsT:ION o 7 1 21 ANIMAL NO. MEAN BODY WEIGHT (grams) 665577556667 (vp) 287-.6 306-.8 314-.8 321.6 sSDp ((DoAaYY 112228)) 665577556689 (ve) 319-.2 341-.4 366-.6 337-'.6 SsDp ((DoAvY 112204)) 665577557701 320626..95 322085..87 333185..85 322950..70 SSDD ((DDAAYY 112232)) 665577557723 3219860.00 334089..57 334037..18 334133..49 SSDD ((DDAAYY 112212)) 665577557745 (ve) 33-53 341-00 328-.8 340-" .3 SsDp ((PoAnYy 112234)) 665577557767 238431..88 337108..36 335373.148 336303..94 SSDD ((DDAAYY 112212)) 665577557798 (uP) 268-.7 309-.5 336-.5 326-".1 sSDp ((oDaAvY 112241)) 665577558801 322865..27 332028.l06 333132..74 334001..39 SSDD ((DDAAYY 112223)) 665577558823 (ve) 316-.0 336-.4 336~.1 347-".7 sSDp ((oDaAvY 112241)) ~ 665577558854 321632.096 323937..83 338046..68 334056..08 SSDD ((DDAAYY 112253)) LAaCTvAsT:ION 07 7-4 wer 021 ANIMAL NO. MEAN BODY WEIGHT GAINS (grams) 657566 657567 (ve) 1-9.2 8-.0 6-.8 34=.0 SsDp ((DoAaYY 112220)) 665577556689 (ue) 22-.2 25-.2 29-.0 18=.4 SsDp ((DpAaYy 112204)) 665577557710 2322..38 1163..71 2-153..51 2223..85 SSDD ((DDAAYY 112223)) 665577557723 3B03075 sallas 06113 2157..45 SSDD ((DDAAYY 112221)) - 656577557745 (ve) 5= 7-12-2 1-s 5=.0 Sspo ((DaAvY 11223)) - 665577557776 238a.85 1125.:92 -03l.45 1499..61 ssDD ((DDAAYY 112212)) 656577557798 (ve) 40-.8 27-.0 -10-.4 57=".4 sSpD ((mDaAyY 112241)) 656577558801 2s3a0z5 u2l1y8-1016.56 11461112 sSpp ((DbAAYY 112232)) 665577558823 (vp) 20-.4 0-.3 11-.6 31=.7 sSDp ((DoAaYr 112241)) 657584 657585 317 10908 5 a0l0a 3245.021 sspD ((DpAaYy 112253)) --~ 196 Company Sanitized. Does not contain TSCA CBI 25231: OneGeneration Reproduction Study in Rats --~ DuPon9763 --~ APPENDIX H INDIVIDUAL FOOD CONSUMPTION OF P; MALE RATS 97 -- Company Sanitized. Does not contain TSCA CBI H-25231; One-Generation Reproduction StuindRaiys DuPont763 ~~ INDIVIDUAL FOOD CONSUMPTION OF P; MALE RATS EXPLANATORY NOTES Notes TestDays 1-75 = Premating period Test Days 76:90 = Cohabitation period Abbreviations AK = Accidentally Killed SE = Sacrificed inextremis;data excluded from group means. (Group 1-0, Animal No. 657409) - = NoDaa --~ -- - ms Company Saniized. Does not contein TsScChA CBI 'H:25231: OneGeneratioRneproduction StudyinRats DuPon.9763 --~ INDIVIDUAL FOOD CONSUMPTION (grams/day) OF 2; MALE RATS GROUP: 1-0 DOSE: 0 MG/KG/DAY onaTyEsST: ANIMAL NO. 656577339921 656577339938 656757339956 657397 665577339989 665577440010 656577440023 66557740054 665577440067 665577440089 ~~ 657410 1-8 8-15 15-22 22-20 29-36 36-43 43-50 2276.000 2266.088 2280.042 2280.172 2308.68 2297..36 2218..78 2287051 2288.03 2380;s 2327:.29 233940 2391034 33220 2236048 2253.71 226588 2264.189 2276.142 2261..53 2267.23 2286137 2236..12 227.l4s 2238s0 224863 3296.50 229346 2265.42 2253..24 2266..20 2276..31 2278.96 2257..40 2274.14 2225024 2232.057 2255.036 2265..04 2275.036 2256..35 2268.51 233073 2380.16 236.70 230.27 2a9l.a4 231230 238277 22661031 22960.10 22980077 3270.38 3320013 2300074 330088 22760066 2267..38 2285l7s 2295..48 3260.84 2286..71 2258.39 220716 22870.76 3208a8 327s5 321573 2351.s9 226944 95 Company Sanitized. Does not contain TSCA CBI F-25231: OneGeneration Reproduction Study in Rats DuPon9763 ~~ INDIVIDUAL FOOD CONSUMPTION (grams/day) OF P; MALE RATS GRovR: 1-0 eee DOSEe: e0 MG/KG/DAY onaTvEsST: 50-57 57-64 64-71 1-71 ANIMAL NO. 665577339912 656577339938 657395 665577339976 656577339998 656577440010 656577440023 665577440045 665577840067 --_ 665577440089 657410 2289.054 2290.059 2277..38 2288.35 3a1l1e 3s0o8s 22890161 2309.56 27.0 25.5 281 a 27.9 26.1 26.7 -a 23000.94 2290006 2292..52 2258..32 2220029 2269.040 2270.19 2251034 2266..32 2266..36 2285..87 2255..28 32300065 3254.32 3283199 2352083 3301098 3301047 23321192 23900060 235a0 2350.71 2342118 2259.094 2267.045 SE 2(8D.A0Y 60) 26-.5 26-.5 --~ a No data due to weighing error on Test Day 64. 20 Company Sanitized. Does not contain TSCA CBI H-25231: OneGeneration Reproduction Study in Rats DuPont9763 --~ INDIVIDUAL FOOD CONSUMPTION (grams/day) OF P; MALE RATS GROUP: TII-0 DOSE: 75 MG/KG/DAY oNDTAEYSST: ANIMAL NO. 665577441167 665577441189 665577442210 665577442223 665577442254 665577442267 656577442298 656577443310 665577443323 --~ 657435 1-8 8-15 15-22 22-29 29-36 36-43 43-50 2278.096 2225..21 22.671 2278.13 2268.21 2268.48 2278..80 224a125 2255..54 2266.54 2267..65 2229..38 2269.s8 2259.l8s 2206055 2278.007 2279.034 2278.037 2391.s4 2380.34 2269:.28 2264.16 2250..56 2316.51 2370.56 32290.68 2381.s1 2361.02 2a8l0o1 3303.s8 33s1l2z 330.s2 3328010 3329..80 3326332 220569 2265.18 2268.38 2278.82 3321.93 221953 2218.61 2206059 2370..05 2327.55 330372 335082 23925.85 2393000 2286077 2298011 220738 332302 3323526 3323020 2381036 23700039 3320087 331311 33138 3351s0 338253 33510s 231 2200 201 2207 2813 247 2602 --_ 201 Company Sanitized. Does not contain TSCA CBI 25231: OneGeneration Reproduction Study in Rats DuPont9763 ~~ INDIVIDUAL FOOD CONSUMPTION (grams/day) OF Ps MALE RATS Grove: TII-0 DOSE: 75 MG/KG/DAY onDTAEYSST: ANDNAL NO. 665577441176 665577441189 665577442210 665577442223 656577442254 665577442267 656577442298 665577443301 665577443332 --~ 657435 50-57 57-64 64-71 1-71 2278.102 3209..40 32080.74 2278.07 2295061 2360.81 2259.026 2258.26 236012 239100 2380181 237050 23700056 2382.04 2391010 237037 3308017 2307088 2396034 330671 2297085 229.046 228960 221838 3300013 333:030 3302s7 22965 33020045 331048 33123 3300s 3305a8 3372.155 a3086 331a0 206 280 250 242 --~ 0 `Company Sanitized. Does not contain TSCA CBI H25231: OneGenersion ReproductionStedyinRats DuPon%763 ~ INDIVIDUAL FOOD CONSUMPTION (grams/day) OF 2; YALE RATS Grove: v-0 DOSE: 500 MG/KG/DAY onaevsst: AIL Ro. 86557744421 665577444443 885577444465 s65577444487 8G5577445409 655774a5512 885577445543 665577445565 656757445578 ~ 665577445590 18 sas 1s-22 22-29 29-36 36-43 43-50 2260.06 262 2250.35 272 m27a. sea a20.79 285 221827 2906 w28s2 30.4 2a7.l2 332 2255576 211 2275.52 216 2s6l0s 217 226953 aus 2372.18 a2 238.00 242 2352.088 227 2 Za 275 2221s 37.7 emzlieeae 2as4l9o 30a 226677 2908 226647 217 225591 210 2266.24 369 2266.60 ssa 2287.4 mls 2298015 2004 3228.04 287 223881710 228777 280 225097 203 s2e3a7 2.6 a saz as 2210s9 25a 2296016 253 229649 248 216332 245 S20057 20 s26a1 2a semse as 32483 mz 326937 286 32103 283 32618 268 223387 z3e2ds zalesn. z19a4 223a8 228412 221306 --~ 0 Company Saniized. Does nol contain TSCACEI H-25231: One-Generation ReproductionStudy inRats DuPont9763 ~~ INDIVIDUAL FOOD CONSUMPTION (grams/day) OF 2, MALE RATS Grove: v-0 DOSE: 500 MG/KG/DAY onaTvEsST: ANIMAL NO. 665577404421 665577404434 665577444465 665577444478 665577445409 665577445521 665577445503 665577405565 665577445587 ~ 665577446509 50-57 57-64 64-71 1-71 22070.00 2227010 2206095 22001.83 3275.32 32270.56 320867 320885 222673 2227006 22513s 2226..44 2265.057 2275..08 2246.02 2254..49 226651 228751 22871.38 2218.05 236.17 a28l2s 2a7l.s3 2289.71 2273.42 22960.77 228623 221480 220.35 2283.040 2200020 227433 2362..76 2315.67 234800 3263.79 2271.99 2265.35 228369 22:1332 -- Eo Company Saniized.Doesnot contain {SCA CBI H:25231: OneGeneration Reproduction StudyinRats DuPont9763 --~ INDIVIDUAL FOOD CONSUMPTION (grams/ay) OF P; MALE RATS GROUP: VIT-0 DOSE: 3500 MG/KG/DAY onDmAeYsSt: ANDOL NO. 665577446676 665577446698 665577447710 665577447732 665577447754 665577447776 665577447798 665577448810 665577448832 ~ 656577448845 1-8 8-15 15-22 22-29 29-36 36-43 43-50 2200.65 1292..10 2201.18 22411.77 2276.15 2263.78 2261.86 226220 2230.74 2204031 2253.85 2277..66 228646 2213.091 22138s 2157..87 2159.079 22112s 2253.27 222425 211906 2275.32 22220.82 22970.63 22271.48 2267..28 2289040 2291..90 2281020 2118.s6 1285..80 2155..33 2250.87 22060001 2203.071 2276..64 2280.049 322.43 3244.21 3223.159 AK 2(4D.A0Y 42) 26-04 2270058 2247..27 2238.74 2295005 22030.83 2215.20 23020.82 2292084 3205..64 3226..64 2363..40 32321.82 324a2 226127 32250.95 3214..27 22840.17 22060.75 2272..29 32049s 2263.89 2278.80 2272.34 2391.32 2391.82 2374.13 2308089 2285.053 --~ 5 Company Sanitized. Does not contain TSCA CBI H25231: One-GenerationReproduction Study inRais DuPont9763 ~ INDIVIDUAL FOOD CONSUMPTION (grams/day) OF P; MALE RATS GROVR: VII-0 DOSE: 3500 MG/KG/DAY ona7vsssT: ANIMAL NO. 665577446667 665577446689 665577447701 657472 665577447733 665577447756 657477 665577447789 665577448801 665577448832 ~ 665577448835 50-57 57-64 64-71 1-71 2200.20 2260.s7 2262.070 2252.32 23800a 2200.035 22891086 225:62.9 22331ss 21281a8 225006 223164 2270.032 2327533 236.14 221738 220sa 227351 328111 z20a07 26-00 29%.6 26-.6 24-.9 3223.46 229328 3221.13 22920.97 22550010 237813 23551.50 2314037 2256050 2370.81 Fp 1(7D.A2Y 66) 28-.2 2383163 2e6l0s7 2391020 3208065 ~~ 6 Company Sanitized. Does notcontain TSCA CBI F-25231: One-Generation ReproductionStudy inRats --_ DuPont9763 ~~ APPENDIX I INDIVIDUAL FOOD CONSUMPTION OF P; FEMALE RATS DURING PREMATING ~~ 07 Company Sanitized. Does not contain TSCA CBI 25231 One-Generaion Reproduction Study in Rats DuPont9763 --~ INDIVIDUAL FOOD CONSUMPTION OF P; FEMALE RATS DURING PREMATING EXPLANATORY NOTES Notes TestDays 1-75 = Test Days 76-90 = Abbreviation - = NoData Premating period Cohabitation period -- --_ 08 -- Company Sanitized. Doesnot contain TSCA CBI 25231: One-Generation Reproduction Studyin Rats DuPont-9763 ~ INDIVIDUAL FOOD CONSUMPTION (grams/day) OF Py FEMALE RATS DURING PREMATING GROUP: TI-0 DOSE: 0 MG/KG/DAY onDTAEYSST: ANDAL No. 656577445912 665577449934 665577449956 665577449987 656577459090 665577550012 665577550083 665577550056 665577550087 ~ 665577551009 1-8 8-15 15-22 2229 29-36 36-43 43-50 1196.001 2126..42 1178.20 1188.76 2168.28 216..88 1157..81 f1e660 1177..45 118874 119821 1198.7 1189.24 1177..96 117648 117600 1167..68 1117..80 1178.s8 1189.11 1177.32 l1e.a8 1156.17 1199l.00 1208033 210843 1178.56 1187..71 1197030 11903 2109021 11886s 2221.71 1209.64 1189.21 11575 115430 116524 1is6l.e0 1167..01 1155..78 115535 11950.46 1178.18 1178.s9 1i8s0s 2201.62 1281.15 2116..46 120a.78 1185.97 12062s 1225.50 2171.89 1158.56 1175..86 m17s09 1190039 12120 2201037 220706 1188.98 1198.05 11s3i7 1s7i3z s15l.a4 118675 1153.89 1115.58 1163038 --_~ ere 2% eterno `Company Sanitized. Does not contain TSCA CBI 25231: OnGeeneration Reproduction Study in Rats DuPon9763 ~ INDIVIDUAL FOOD CONSUMPTION (grams/day) OF 2, FEMALE RATS DURING PREMATING GROVE: TI-0 DOSE: 0 MG/KG/DAY _ onaTvSsT: 50-57 57-64 64-71 1-71 ANIL NO. 665577445921 665577445543 665577448956 665577449987 665577540909 665577550012 665577550083 665577550065 665577550087 ~ 665577551009 1l6.e8 1 162 117698 1169.08 1m846 118724 11883 1188.a0 1121 117955 117850 1177.66 w1a4 1178s8 w19o1 1187.85 1178.99 118765 1189l2a 11990002 1175.61 116563 1155..49 1155..68 1w90s3 118875 1189l78 1198025 3 1 119530 115728 119s7. 21910ss 1189173 1178.78 119933s l17s.3 1164.64 11830s 1174.s8 ------ 20 ee-- e eee -- Company Sanitized. Does not contain TSCA CBI 125231 One GenerationReproduStcudtyiinoRants Dupo 763 --~ INDIVIDUAL 700D CONSUMPTION (grams/day) OF 7, FEAL ATS DURING PREMATING Grove: 70-0 Dose: 75 U/KG/OAY on'amntsss: ma vo. prepsit1ees1d6 Gp5ir7sa5ti2eo0! SSGr77a20032a pGierreaee pGEr7ri3ae2sd0 SGE377733331 ~ Gpr3e3a 18 sas 1522 22-29 29% 6-3 43-50 1ms0eiooob1nEs enLsgio1Enos 1ma3m9sin1wa2d a1ousan fD2Gs7 Gd1oesss 2Gw0sdm daloieaaa 0eensa 11w30ss 21 100s DBJo6es SIdesio bmdaae addmeeasn 1aa9s3s sa 1ns 11edse 3 iifs sidmeoes iGleessn Delesoa fd0eeas 1 daaea a1ass i dioa ddioseoo zh1iass sReuSoe ha1vnse ah1ans 1o1n9md i9ae0d% dldesos Iafsiinss ledaeass l2ao0ssa l1ue0ls 11n40n WB33ode0n5 0 aie adawe mass L1ad aes --_ a GompanySanitzed.`DoesnotcontTSaCAiCBnI F-25231: One-GeneratiRoenproduction Study inRats DuPon9763 ~ INDIVIDUAL FOOD CONSUMPTION (grams/day) OF P, FEMALE RATS DURING BREMATING GROVE: TV-0 DOSE: 75 MG/KG/DAY onaTvEsST: ANIMAL NO. 665577551176 665577551198 665577552201 665577552223 657524 656577552265 665577552278 665577552390 665577553312 665577553331 ~ 657535 50-57 s7-64 64-71 1-71 1m8.o0 1197.19 1186.60 1187.53 2108077 2137ss 118741 11983 71886 116a6 1178.71 s1l7ss 1168143 118s3. 117s.6 1168.84 2170.27 212802s 1187128 2107161 va5s 119a1 v183a 1u8n0 119608s 2107076 1196l23 210659 11806 2190040 118837 118883 119904 118765 11685s 119874 2108083 2109009 1198l0s 2109163 --~ 0 N -- Company'SaSanti nDioestnoticonztaineTSCdAC.ay `H25231: OneGeneration Reproduction Std in Rats DuPont9763 ~ INDIVIDUAL FOOD CONSUMPTION (grams/day) OF P; FEMALE RATS DURING PREMATING Grove: VI-0 DOSE: 500 MG/KG/DAY. oNDTAEYSST: ANIMAL NO. 665577554412 665577554443 656577554465 665577554487 665577555409 665577555521 665577555534 657555 665577555576 665577555598 ~ 657360 1-8 8-15 15-22 22-29 29-36 36-43 43-50 1 15.9 1166.38 1193.3 1178.38 220014 1178..44 1177.28 116610 1176.021 2108016 21030%5 2200026 1188..36 2109..62 1155.08 11s6l0a 117.03 11678 1178.18 1176.30 116s8 11750.66 1194133 211616 119603 12070.80 2151.10 2150.38 1165s6 1183071 1186lae 119835 118874 1155..52 1164171 1l6e0s s1l6a3 1178.37 1197031 116884 1178.03 11881a 1188039 1156.54 1166..34 211860 2212..23 118860 1168.37 126001 s20l0s5 211900 2137030 2192055 1270.32 2107.21 1176.s4 11s84 1186.s4 2l00a8 2138.93 126052 1168.53 2106s 1271.s8 220017 12831% 220588 128;6 22000 -- 0 Company Sanitized. Does not contain TSCA CBI H-25231: OneGeneratiRoenproductionStudyinRats DuPon9763 --~ INDIVIDUAL FOOD CONSUMPTION (grams/day) OF P, FEMALE RATS DURING PREMATING GROUP: VI-0 DOSE: 500 MG/KG/DAY. onDSAYTS: ANIMAL NO. 665577554412 665577554434 656577554465 665577554487 665577555409 665577555512 665577555530 665577555565 665577555578 ~ 665577555690 50-57 57-64 64-71 1-71 1v823 11863 118771 118726 1l7e 11990010 21080a1 1189d1 115676 116635 s1l577 i1s6a6 l16s2 21613 a2s0l0 2i0s0l7e 1163 116635 116427 1157139 wwai 118727 1p6h4 117a6 116s3 119522 s1l6s6 1187180 125037 2106050 113666 1207018 116s5 1186s3 s1l6o6 117a1 23s0l6a 210810 11890 21270:28 --~ me Company Sanitized. Does nota contac in TSs CA CBI H:25731:OneGeneration Reproduction Study in Rats DuPont9763 ~ INDIVIDUAL FOOD CONSUMPTION (grams/day) OF P, FEMALE RATS DURING PREMATING GROUP: VIII-0 DOSE: 3500 MG/KG/DAY onDTAEYSST: ANDMAL NO. 665577556667 665577556698 665577557710 665577557732 665577557754 656577557776 665577557758 656577558810 665577558823 ~ 665577558845 1-8 815 15-22 2229 29-36 36-43 43-50 l13s.0 1174s7 l1e6i6s 2170.s8 1177..80 11g5l.s9 1176..02 11505 1168128 116745 211337 1179.090 1179.53 1186.30 1136083 1126l5e 11s9l0s2 i1s6l.a2 1138s8 1175.34 115639 1157.4 11.807 1177.8 1215.a0 116879 1117.37 116783 l2a0o0 1186.66 117821 1168.s4 2180.32 1116.52 1282..67 119053 w18z.4 p18z1 a17l.a6 2197.8 1179s1 1174.96 w15r.1 11s2 i1e7s7 1s7l0s 210827 212s 111700ss 115651 117058 7 173.09 1251.82 1178.84 2189.80 1177..84 11501 1s8lsa 1189l33 12022 21l8a7 11892 1g8l7e 113081 118905 1159.081 1188.s4 1272.05s 1177.71 1157.183 -- 215 Company Sanitized. Dossnot contain TSCA ll H25231: One-Generation ReproductionStudyin Rats DuPont9763 --~ INDIVIDUAL FOOD CONSUMPTION (grams/day) OF Py FEMALE RATS DURING PREVATING GROVE: VIII-0 DOSE: 3500 MG/KG/DAY onDTAEYSST: ANDSAL NO. 665577556676 665577556698 663577557710 656377557732 665577557705 665577557776 665577557789 665577558810 665577558832 ~ 665577558854 50-57 57-64 64-71 1-71 21050.08 1151..46 1176.s6 1158..60 1197077 119dls ssllss 11813s 19ls 112981 1158.l9s 117d.8 1a6a 1166s4 a1i6l2s 11670.15 119708 1167s1 s1l9os 1s7l0s7 1868 118726 117722 1187133 116823 l18e3 117884 11875030 1878 s1l7a0 i2s0s4 118721 189503 11667 21010.03 1179.00 v1812 11683s 1 18216ails Eg Company Sanitized. Does not contain TSCA CBI H:25231: OneGeneration Reproduction Study in Rats --~ DuPont9763 --~ APPENDIX J INDIVIDUAL FOOD CONSUMPTION OF P; FEMALE RATS DURING GESTATION --_ 207 `Company Sanitized. Does not contain TSCA CBI F-25231: One Generation Reproduction Study in Rats DuPont.9763 ~~ INDIVIDUAL FOOD CONSUMPTION OF P FEMALE RATS DURING GESTATION EXPLANATORY NOTES Abbreviations NP = No litter delivered; data excluded from statistical analysis. - = NoDaa ~~ --~ --- = Company Sanitized. Does not contain TSCA CBI H25231: One-GeneratioRneproduction Studyin Rats DuPon9763 ~ INDIVIDUAL FOOD CONSUMPTION (grams/day) BY Py FEMALE RATS DURING GESTATION GROUP: 11-0 DOSE: 0 MG/KG/DAY GeDsAmYaSr:ron 0-7 74 ue oz ANDIAL No. 665577449921 22679 32015 228.20 2282.25 665577449934 22350.01 225577 2a6l5s 2254.s8 665577449965 (xP) 220077 2200082 1225.86 1282..87 663577449987 2236s3 2265060 2275..86 2256.10 665577540309 2257 225073 2263.22 226214 665577550021 22028 22001 82026 2233.58 665577550034 2220058 226027 2248.195 z2a4.6 665577550065 2221047 2225088 2267.34 2253.53 665577550078 220056 225644 2256.04 2255..17 ~ 656577551009 (xp) 7170 11s.l4s 126381 120708 --_ Eg Company Sanitized. Does not contain TSCA CBI F-25231: One-Generation ReproductionStudy inRats DuPont763 ~~ INDIVIDUAL FOOD CONSUMPTION (grams/day) BY P; FEVALE RATS DURING GESTATION Grove: 19-0 DOSE: 75 MG/KG/DAY GeDsAtYaST:Ion 07 714 wa on Ane No. 656577551176 2257.6 2a5l.s7 226.19 22250.64 665577551189 (2) 2-s 2-.8 2~7 2-.4 657520 2.3 237 208 23.9 65g5775522218 2936..69 205 2262.029 24-.7 665577552230 22060 2199573 23000078 22090113 656577552265 02056 223135 213521 2129.64 665577552278 a2l0s5 220288 2200053 224376 a575250 6575300 . . . - . M z - 665577553312 2295.90 221564 2255.26 2255.54 --_ 665577553343 120577 1268074 230309 220161 657535 22 2003 263 2308 --_ J3 uEvceiadletcnoucleeartroioforn,sc.opfuoloadtidoantawavserenotnotobsreercvoerdd;edthoenre7f0o.re,Datnao for 0-76 excluded from gestation data were the Collected. m CompanySanitized.DOGS:otco-- ntaiTSnX H25231:One GenerationReproduction SwdyinRats DuPon976s ~ INDIVIDUAL FOOD CONSUMPTION (grams/day) BY P, FEMALE RATS DURING GESTATION Grou: VI-0 DOSE: 500 MG/KG/DAY GeDsATYAST:ION 1 7 wen oa ANDHAL NO. a65s7r5s4a2a 637543 220908 220097 23-.2 21-.6 Bi ma 2s as 656577554445 857546 2a0l2s 222641 224033 22089 Ios 240 205 228 885577534478 857349 mZilles 225028 22930 222509 Ble m2 2m 22 6ss55s77s55s55102b0 a--s -2a - 2s 2-z7 658577555543 n2l3a 2ml2s 2aa7 226s1 665577555565 l3s 22023 229a 22103 ~ 685577535578 (vp) 557559 w=a ls 1289 2-.8 255 2-00 217 657360 2s 268 2907 20.0 ~ 23 rBeeiindaelncedelofivceorpeadlpartiioonr vtaoscnooltlecctbsieornveodf: Getshteraatfioorns,Danyo21esdtaattai.on data were oilecred 2) Company Sanitzed. Does not contain TSCA CBI 1.25231:One-Generation Reproduction Study in Rats DuPon.9763 ~ INDIVIDUAL FOOD CONSUMPTION (grams/day) BY 7; FEMALE RATS DURING GESTATION eGerovee: vIIZ-0 D082: 3500 MG/KG/DAY caTsaTsAT:ION 07 710 wen on AIHA YO. Gaasr7s5e6r60 me) s6375e68 am 2-08 nS 22-.2 ma 14-.6 23 13..2 2a 2a 1s 205 27 e85s775s77018 857572 $-4 2.2 1s 195 2o2 27 2z04 20.8 663377557743 G377577s6 we) Z2i5o 197 smlz 208 2m0a 2006 a25s4 20.4 30 ses 82 2603 8S&5o37r75a57r79e7 me) 1B7r.1 i laes ae mllesz 2008 1a6i.a6 20.8 63G67o7r55e88s012 me) 322502 alo 3 s1a6s9 m20o9 161 2238s3 1810 ~ 888555777555888354 22066 Be amiaa mo 221455s 2s m2iss 200 -- + ovCiodelelemeerceteodf comlation was not observed; therefore, no gestation data vere JE = CompanySaniDoies pzotecondtai.nT SCACBI 25231: One-Generation Reproduction Study in Rats DuPont9763 --_ APPENDIX K INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA INP; MALE RATS --~ J nw Company Sanii-- zed. D-- oss n-- ot con-- tain TSCA CBI 125231: One-Generaton Reproduction Study in Rats DuPont.9763 ~ INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN P; MALE RATS EXPLANATORY NOTES Notes TestDays 1-75 = TestDays 76-90 = Premating period Cohabitation period PN - T5 Gompany Senitized, Doss notcontainTSCA CE! 125231: OGneenerationReproduction StudyinRats DuPont9763 ~ INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN Py MALE RATS GRovR: I-0 DOSE: 0 MG/KG/DAY JE ANDMAL NUMBER OBSERVATION OFBISRESRTVEDDAY LOABSSETRVDEAYD -------_- 657391 NSOACARBINFOIRCMEADLIBTYIEDSESDIEGTNECTTEESDT DAY 114 657392 AALLOOPPEECCIIAA BLOETFHT FFRROONNTT LPEAGH((SS)) 1855 350 SACRIFICED BY DESIGN TEST DAY 114 657393 AALLOOPPEECCIIAA BBOOTTHH FFRROONNTT LPEAGW((SS)) ALOPECIA LEFT FRONT PAWS) 2299 7788 8s 85 SACRIFICED BY DESIGN TEST DAY 114 657394 NSOACARBINFOIRCMEADLIBTYIEDSESIDGENTETCETSETD DAY 114 657395 NSOACARBINFOIRCMEADLIBTYIEDSESIDGENTECTTEESDT DAY 114 ~~ 657396 N`SOACARBINFOIRCMEADLIBTYIEDSESIDGENTECTTBESDT DAY 115 657397 NSOACARBINFOIRCMEADLIBTYIEDESSIDGENTECTTEESDT DAY 115 657398 NSOACARBINFOICREMDALIBTYIEDSESDIGENTECTTEESDT DAY 115 657399 NSOACARBINFOIRCMEADLIBTYIEDSESDIEGTNETCETSETD DAY 115 657400 NSOACARBINFOIRCMEADLIBTYIEDSESIDGENTETCETSETD DAY 115 657401 NSOACARBINFOIRCMEADLIBTYIEDSESTDGENTETCETSETD DAY 116 657402 657403 NSOACARBINFOIRCMEADLIBTYIEDSESIDGENTETCETSETD DAY 116 A`ALLOOPPEECCIIAA BBOOTTHH FFRROONNTT PPAAWW((SS)) SACRIFICED BY DESIGN TEST DAY 116 . 684 175 657404 NSOACARBINFOIRCMEADLIBTYIEDSESIDGENTECTTEESDT DAY 116 657405 NSOACARBINFOIRCMEADLIBTYIEDSESIDGENTETCBTESDT DAY 116 f 657406 NSOACARBINFOIRCMEADLIBYTIEDSESIDGENTETCBTESDT DAY 117 - Eg CompanySanitized.Does notcontain TSCA CBI 425231: OGneeneration Reproduction Sy in Rts Dupon9763 ~ INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN 2; MALE RATS = _-- Grou: 1-0 DOSE: 0 MG/KG/DAY o Ano wMBo ER o onsERvATIONUo CFaISREsTRvEDDAY LOABSSiTERVDdEAYD 57407 NSOACARBINFOIRCMEADLIBTYIEDSESIDGENTETCETSETD DAY 117 657008 NSOACRAIBFNIOCREMADLIBYTIEDSESIDGENTETCETSETD DAY 117 657605 SSSOOoRRsEE BReOIcTGkHHTSHSOHUOLUDLEDRE(RS()S) I1pH0H 53360 SACRIFICED IN EXTREMIS TEST DAY 60 65740 NSOACARBINFOIRCMEADLIBTYIEDSESDIEGTNECTTEESDT DAY 117 -- --_ eee ------------ ieee 5StCeomppanpy iSnaneiDrolorsinsoztcoentdai.nTSSCoAACBI 25231: One-GenerationReproduction Study inRats DuPont9763 ~ INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN Py MALE RATS GROUP: ITI-0 DOSE: 75 MG/KG/DAY ANIMAL NUMBER OBSERVATION OFBISRESRTVEDDAY OLBASSETRVDEADY 657416 NSOACARBINFOICREMDALIBTYIDEESSIDEGTNECTTEESDT DAY 114 657417 NSOACARBINFOICREMDALIBTYIDEESSIDGENTECTTEESDT DAY 114 657418 NSAOCRAIBFNIOCREMADLIBTYIEDSESDIEGTNETCETSETD DAY 114 657419 NSAOCRAIBFNIOCREMADLIBTYIEDSESIDGENTETCETSETD DAY 114 657420 NSAOCRAIBFNIOCREMADLIBTYIEDSESIDGENTETCETSETD DAY 114 657421 SNAOCRAIBFNIOCREMADLIBYTIEDSESIDGENTETCETSETD DAY 115 ~ 657422 AALLOOPPEECCIIAA BBOOTTHH FFRROONNTT LPEAGW((SS)) SACRIFICED BY DESIGN TEST DAY 115 657423 AALLOOPPEECCIIAA BBOOTTHH FFRROONNTT PLEAGW((SS)) SACRIFICED BY DESIGN TEST DAY 115 657424 SNAOCRAIBFNIOCREMDALIBTYIDEESSDIEGTNETCETSETD DAY 115 657425 NSAOCRAIBFNIOCREMADLIBTYIEDSESDIEGTNETC2TSETD DAY 115 657426 NSAOCRAIBFNIOCREMADLIBYTIEDSESIDGENTETCETSETD DAY 116 657427 NSAOCARBINFOIRCMEADLIBTYIEDSESIDGENTETCETSETD DAY 116 657428 NSOACARBINFOICREMDALIBTYIDEESSIDGENTETCETSETD DAY 116 3366 111s5 578 1155 -- 27 Company Sanitized. Doesnotcontain TSCA CBI. H:25231: OneGeneration Reproduction Study in Rats DuPont9763 ~ INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN P; MALE RATS Grove: III-0 DOSE: 75 MG/KG/DAY ANIMAL NOMBER OBSERVATION - 657429 AALLOOPPEECCIIAA BBOOTTHH FFRROONNTT LPEAGW((SS)) ASLAOCPREICFIIACERDIGBHYTDEFSRIOGNNT TPEAWS(TS)DAY 116 657430 NSOACARBINFOIRCMEADLIBTYIEDSESIDGENTECTTEESDT DAY 116 657431 AALLOOPPEECCIIAA BBOOTTHH FFRROONNTT LPEAGW((SS)) SACRIFICED BY DESIGN TEST DAY 117 657432 NSOACARBINFOIRCMEADLIBTYIEDSESIDGENTECTTEESDT DAY 117 657433 NSOACARBINFOIRCMEADLIBTYIDEESSIDGENTETCETSETD DAY 117 ~~ 657435 NSOACARBINFOIRCMEADLIBTYIEDSESDIEGTNECTTEESDT DAY 117 657596 NSOACARBINFOIRCMEADLIBTYIEDSESIDGENTECTTEESDT DAY 117 OFBISRESRTVEDDAY 125 108 OLBASSETRVDAEYD 1196 116 1177 1177 -- 28 CompanySanit,ized. Doesnotcor!tainTSCACBI 25231: One-Generation ReproductionStudyinRats DuPont9763 ~~ INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN 2, MALE RATS Grove: V-0 DOSE: 500 MG/KG/DAY. ANIMAL NUMBER OBSERVATION OFBISRESRTVEDDAY OLBASSETRVDEADY 657841 657442 657443 657400 657445 657446 --_ 657447 657448 657449 657450 . 657451 657452 SNAOCRAIBFNIOCREMADLIBTYIEDSESIDGENTE7C2TSETD DAY 114 SNAOCRAIBFNIOCREMADLIBTYIEDSESIDGENTETCETSETD DAY 114 SNAOCRAIBFNIOCREMADLIBTYIEDSESIDGENTE7C2TSETD DAY 114 NSOACARBINFOIRCMEADLIBTYIEDSESIDGENTETCETSETD DAY 114 NSOACARBINFOIRCMEADLIBTYIEDSESIDGENTETCETSETD DAY 114 NSOACARBINFOIRCMEADLIBTYIEDSESIDGENTETCETSETD DAY 115 SNOACARBINFOIRCMEADLIBTYIEDSESIDGENTE7C2TSETD DAY 115 AALLOOPPEECCIIAA BLOETFHT FFRROONNTT PPAAWW((SS)) ASLAOCPREICFIIACELDEBFYT DFREOSNITGNLETGE(SST) DAY 115 NSOACARBINFOIRCMEADLIBTYIEDSESIDGENTETCETSETD DAY 115 AALLOOPPEECCIIAA BBOOTTHH FFRROONNTT LPEAGW((SS)) AALLOOPPEECCIIAA LLEEFFTT FFRROONNTT LBEAGW((SS)) SACRIFICED BY DESIGN TEST DAY 115 SNAOCRAIBFNIOCREMDALIBTYIDEESSIDGENTETCETSETD DAY 116 NSAOCARBINFOIRCMEADLIBTYIEDSESIDGENTETCETSETD DAY 116 10969 11959 106 115 5500 778 110066 111s5 - --~ r-- e --------2--eCoT mspanay Ste-- nieized. D-- oes not co-- enetieneTmSeCACB! F-25231: OneGeneration Reproduction Study in Rats DuPont9763 ~~ INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN 2; MALE RATS e eee GROUR: V-0 DOSe E: 500 MG/KG/DAY ANTMAL NUMBER OBSERVATION OFIBRSSETRVEDDAY LOABSSTERVDEADY rn meee meses in Seeaeetetree 657453 NSOACARBINFOIRCMEADLIBTYIDEESSIDGENTETCETSETD DAY 116 657454 NSOACARBINFOIRCMEADLIBTYIEDSESIDGENTETCETSETD DAY 116 657455 SNOACARBINFOIRCMEADLIBTYIEDSESIDGENTETCETSETD DAY 116 657456 NSOACARBINFOIRCMEADLIBTYIEDSESIDGENTETCBTSETD DAY 117 657457 NSOACARBINFOIRCMEADLIBTYIEDSESIDGENTETCETSETD DAY 117 657458 NSOACARBINFOIRCMEADLIBTYIEDSESDIEGTNETCETSETD DAY 117 ~ 657459 AALLOOPPEECCIIAA BBOOTTHH FFRROONNTT LPEAGW((SS)) ? AACLCOIPDEECNITALYLEFKTILFLREODNTTESPTAW(DSA)Y 86 657460 AALLOOPPEECCIIAA BBOOTTHH FFRROONNTT LPEAGW((SS)) : SACRIFICED BY DESIGN TEST DAY 117 85 5500 85 85 229 1177 230 Company Sanitized. Does not contain TSCA CBI H25231: OneGenersionReproductionStodyinRats_ DuPone763 ~ INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN P) MALE RATS Grove: VII-0 DOSE: 3500 MG/KG/DAY ANIMAL NUMBER, OBSERVATION OFIBRSSETRVEDDAY OLABSSTERVDEAYD 657466 SNOACARBINFOIRCMEADLIBTYIEDSESIDGENTETCETSETD DAY 114 657467 LDoINSGCHRAoRTGsEEPENIS RED SSOARCERIFPIECNEIDS BY DESIGN TEST DAY 114 657468 NSOACARBINFOIRCMEADLIBTYIEDSESDIGENTETCETSETD DAY 114 657469 SLSTANACGIRNINEFODIICSEPEDERBIYNEUDMESIYGENLLTOEWST DAY 114 657470 NSOACARBINFOIRCMEADLIBTYIEDSESDIGENTETCETSETD DAY 114 I~ 657471 SAALLOVPAETCIIAONBOTH FRONT PAW(S) STAINED PERINEUM YELLOW SACRIFICED BY DESIGN TEST DAY 115 657472 SaALLOTPUEACTIIAONBOTH FRONT LEG(S) SAFALLCOORPPIEEFCCIIICAAEDRRIIGGBHHYTTDEFFSRRIOOGNNNTT LPEAGW((SS)) TEST DAY 115 657473 NSAOCARBINFOIRCMEADLIBTYIEDSESIDGENTETCETSEDT DAY 115 657474 ASLAOLPIEVCAITAIOBNOTH FRONT PAW(S) ASLAOCPREICFIIACEDBOBTYH FDREOSNITGNLETGE(SST) DAY 115 ia aa 2 52 8500 852 165 i1s6 7 a52 17 885 11155 5se 5si 02 5 657475 SSATCARIINFEIDCENDOSBEYRDEEDSIGN TEST DAY 115 - 657476 SNAOCRABINFOIRCMEADLIBTYIEDSESDIEGTNETCETSETD DAY 116 657477 ANCOCAIBDNEONRTMLAYLIKTIILELSEDDETTESETCTDEADY 42 657478 SNAOCRAIBFNIOCREMDALIBTYIDEESSIDGENTSTCETSETD DAY 116 ~ 657479 SNOACRAIBFNIOCREMADLIBTYIEDSESIDGENTETCETSETD DAY 116 86 86 = Company Sanized. Doesnot contain TSCACBI H:25231: One GenerationReproductionStudy iRats DuPont-9763 ~~ INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN 2; MALE RATS GROUP: VII-0 DOSE: 3500 MG/KG/DAY. ANTAL NUMBER OBSERVATION FOIBRSSETRVEDDAY LOBASSETRVDEAYD 657480 AALLOOPPEECCIIAA RBOITGHHTFRFROONNTTPAPWA(WS(S)) SACRIFICED BY DESIGN TEST DAY 116 657481 NSAOCRAIBFNIOCREMADLIBTYIEDSESIDGENTECTTEESDT DAY 117 657482 SSAALLIIVVAATTIIOONN SFAOLUINVDATDIEOAND TEST DAY 66 657483 SSTTAAIINNEEDD MNOOUSTEHBRBORWONWN SIARCRREIGFUILCAERDREBSYPIDREASTIIGNONTEST DAY 117 657484 SSAALLIIVVAATTIIOONN --_ SSAALLIIVVAATTIIOONN SSTAACIRNIEFDICEPDERBIYNEUDMESIYGENLLTOEWST DAY 117 657485 NSOACARBINFOIRCMEADLIBTYIEDSESDIGENTETCETSETD DAY 117 2326 2592 1301 2321 52 52 6666 669 66 66 232 2345 6554 5649 85 85 --_~ 252 Company Saniized. Doosnot contain TSCA CBI H25231: One GenerationReproduction Sudyin Rats ~ DuPont9763 --_ APPENDIX L IINNDPI,VFIEDMUAALLECLRIANTISCADLUROIBNSGERPVRAETMIAOTNISNAGNADNMDOCROTHAALBIITTYATDIAOTNA ~~ _-- 3 mpany Sanilized. Dos not contain TSCA CB! H25231: One.Generation Reproduction Stuy in Rats DuPont9763 ~~ INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA INP, FEMALE RATS DURING PREMATING AND COHABITATIONa EXPLANATORY NOTES Notes TestDays 1-75 = Premating period TestDays 76:90 = Cohabitation period -- -- --34-- Company Saniized. Does notcontai.n TSCA OBI H25231:OneGenerationReproduction StdyinRats _ DuPo9763 ~ INDIVIDUAL CLINICADLUROIBNSGERVPARETMIAOTNISNGANADNDMOCROTHAALBIITTYATDIAOTNA IN P, FEMALE RATS GROUP: II-0 DOSE: 0 MG/KG/DAY. ANIMAL NOMBER OBSERVATION FIRSTTEDSATY DAYLSAST DAY OBSERVED OBSERVED 657491 NO ABNORMALITIES DETECTED 657492 NO ABNORMALITIES DETECTED 657493 NO ABNORMALITIES DETECTED 657498 NO ABNORMALITIES DETECTED 657495 NO ABNORMALITIES DETECTED 657496 NO ABNORMALITIES DETECTED 657497 AALLOOPPEECCIIAA BBOOTTHH FFRROONNTT LPEAGW((SS)) ALOPECIA RIGHT SIDE(S) 657498 NO ABNORMALITIES DETECTED oy 657499 NO ABNORMALITIES DETECTED 657500 NO ABNORMALITIES DETECTED 657501 NO ABNORMALITIES DETECTED ` 657502 NO ABNORMALITIES DETECTED 657503 NO ABNORMALITIES DETECTED 657508 NO ABNORMALITIES DETECTED 657505 AALLOOPPEECCIIAA BBOOTTHH FFRROONNTT PBAAWW((SS)) ALOPECIA BOTH FRONT LEG(S) 657506 AALLOOPPEECCIIAA BBOOTTHH FFRROONNTT LPEAGW((SS)) ALOPECIA ABDOMEN 657507 NO ABNORMALITIES DETECTED 657508 NO ABNORMALITIES DETECTED 657509 NO ABNORMALITIES DETECTED 657510 NO ABNORMALITIES DETECTED 295 77 5 7 578 736 5 7 88 757 8" 36 --~ _-- 25 Company Sanitized. Does not contain TSCA GBI F-25231: One.Generation Reproduction Study in Rais DuPont9763 ~ INDIVIDUAL CLINICADLUROIBNSGERPVRAETMIAOTNISNGANADNDMOCROTHAALBIITTYATDIAOTNA IN 2, FEMALE RATS Gove: IV-0 DOSE: 75 MG/KG/DAY. - ANIMAL NOMBER OBSERVATION _F_IR_SmT sDtAYomsLA_S_T _DA_Y OBSERVED OBSERVED 657516 NO ABNORMALITIES DETECTED 657517 NO ABNORMALITIES DETECTED 657518 NO ABNORMALITIES DETECTED 657519 NO ABNORMALITIES DETECTED 657520 NO ABNORMALITIES DETECTED 657521 NO ABNORMALITIES DETECTED 657522 NO ABNORMALITIES DETECTED 657523 NO ABNORMALITIES DETECTED 657524 NO ABNORMALITIES DETECTED ~ 657525 ALOPECTA BOTH FRONT PAW(S) 657526 AALLOOPPEECCIIAA BBOOTTHH FFRROONNTT PLAEWG((SS)) 657527 NO ABNORMALITIES DETECTED 657528 NO ABNORMALITIES DETECTED 657529 NO ABNORMALITIES DETECTED 657530 NO ABNORMALITIES DETECTED 657531 NO ABNORMALITIES DETECTED 657532 NO ABNORMALITIES DETECTED 657533 NO ABNORMALITIES DETECTED 3 657531 NO ABNORMALITIES DETECTED 657535 NO ABNORMALITIES DETECTED 8 5 1252 7n --~ EE cemiua pemsnatcomanTeo 25231:OneGenerationReproductionSwudyinRats ___ DuPom9763 ~ INDIVIDUAL CLINICADLUROIBNSGERPVRAETMIAOTNISNGANADNDMOCROTHAALBIITTYATDIAOTNA IN P, FEMALE RATS GROUP: VI-0 DOSE: 500 MG/KG/DAY -_______ _F_IRmST_ sDtAYomL_ sAS_T DAY ANIMAL NUMBER OBSERVATION OBSERVED OBSERVED 657541 NO ABNORMALITIES DETECTED 657542 NO ABNORMALITIES DETECTED 657543 NO ABNORMALITIES DETECTED 657544 NO ABNORMALITIES DETECTED 657545 AALLOOPPEECCTIAA BBOOTTHH FFRROONNTT PLAEWG((SS)) 657546 NO ABNORMALITIES DETECTED 657547 NO ABNORMALITIES DETECTED 657548 NO ABNORMALITIES DETECTED ~ 657549 NO ABNORMALITIES DETECTED 657550 NO ABNORMALITIES DETECTED 657551 NO ABNORMALITIES DETECTED 657552 NO ABNORMALITIES DETECTED 657553 NO ABNORMALITIES DETECTED 657554 NO ABNORMALITIES DETECTED 657555 NO ABNORMALITIES DETECTED 657556 NO ABNORMALITIES DETECTED 657557 NO ABNORMALITIES DETECTED 657558 NOABNORMALITIES DETECTED 657559 NO ABNORMALITIES DETECTED 657560 NO ABNORMALITIES DETECTED 2299 77 . --_ --_--mnmm Company Sanitized. Does not contain TSCA CBI BR C AEN... ~~ INDIVIDUAL CLINICADLUROIBNSGERVPARTEMIAOTNISNGANADNDMOCROTHAALBIITTYATDIAOTNA IN P, FEMALE RATS GROUP: VIII-0 DOSE: 3500 MG/KG/DAY. - _FI_R_STmmDAsYtoaLsAS_T__DA_Y ANIMAL NUMBER OBSERVATION OBSERVED OBSERVED 657566 SHTUANICNHEEDD OPVEERRINEUM YELLOW 657567 NO ABNORMALITIES DETECTED 657568 NO ABNORMALITIES DETECTED 657569 SALIVATION 657570 NO ABNORMALITIES DETECTED 657571 NO ABNORMALITIES DETECTED 657572 NO ABNORMALITIES DETECTED 657573 NO ABNORMALITIES DETECTED 657574 SALIVATION ~ 657575 AALLOOPPEECCIIAA LBEOFTTH RFERAORNTLELGE(GS()S) 657576 AALLOOPPEECCIIAA BBOOTTHH FFRROONNTT LPEAGW((SS)) ALOPECIA ABDOMEN 657577 sALIVATION 657578 NO ABNORMALITIES DETECTED 657579 NO ABNORMALITIES DETECTED 657580 NO ABNORMALITIES DETECTED 657581 NO ABNORMALITIES DETECTED 657562 NO ABNORMALITIES DETECTED 657583 NO ABNORMALITIES DETECTED 657584 NO ABNORMALITIES DETECTED 657585 NO ABNORMALITIES DETECTED 600 611 16 16 51 51 a43 67a1 5577 7n 7 7 5 10 : --_ = Company Sanitizod. Doss not contain TSCACBI F-25231: One-Generation Reproduction Study in Rats --_ DuPon.9763 ~ APPENDIX M INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA INP, FEMALE RATS DURING GESTATION --_ {t----=-- reeamp-- ane y Saf nilzef -- d. Doessnott-- cone tain; TOAcal $1:25231: OneGeneration Reproduction Sty in Rats Dupont.9763 ~ INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN P, FEMALE RATS DURING GESTATION EXPLANATORY NOTES Note `This Appendix contains data from females with evidence of copulation observed. ~ ~ eb2%e eerCiomepanyeSaeniiezedn . Do--ss--not--con--tai--n TSCA CB H:25231: OneGeneration Reproduction StudyinRats DuPont9763 ~~ INDIVIDUAL CLINICAL OBSERVADTUIROINNSG AGNEDSTMAOTRITOANLITY DATA IN P; FEVALE RATS GROUP: 1-0 DOSE: 0 MG/KG/DAY ANTMAL NUMBER OBSERVATION FIRGSETSTDAATYION LDAASYTS DAY OBSERVED OBSERVED 657491 NO ABNORMALITIES DETECTED 657492 NO ABNORMALITIES DETECTED 657493 NO ABNORMALITIES DETECTED 657494 NO ABNORMALITIES DETECTED 657495 NO ABNORMALITIES DETECTED 657436 NO ABNORMALITIES DETECTED 657497 AALLOOPPEECCIIAA BBOOTTHH FFRROONNTT LPEAGW((SS)) ALOPECIA RIGHT SIDE(S) 657498 NO ABNORMALITIES DETECTED --~ 657499 NO ABNORMALITIES DETECTED 657500 NO ABNORMALITIES DETECTED 657501 AALLOOPPEECCIIAA LREIFGTHTSISDIED(ES()S) 657502 NO ABNORMALITIES DETECTED 657503 NO ABNORMALITIES DETECTED 657502 NO ABNORMALITIES DETECTED 657505 AALLOOPPEECCIIAA BBOOTTHH FFRROONNTT LPEAGW((SS)) AALLOOPPEECCIIAA BROITGHHTFRFORNOTNTBALWE(GS()S) 657506 ALOPECIA BOTH FRONT PAW(S) 657507 ALOPECIA LEFT FRONT LEG(S) 657508 NO ABNORMALITIES DETECTED 657509 NO ABNORMALITIES DETECTED 657510 ALOPECIA BOTH FRONT PAW(S) 00 210 21 214 21 00 00 121 22 BE 7 2 o --~ a `CompanySanitized.Doss notcontain TSCACBI H:25231: OneGeneration Reproduction Study in Rats DuPont9763 ~ INDIVIDUAL CLINICAL OBSERVADTUIROINNSG AGNEDSTMAOTRITOANLITY DATA IN P, FEMALE RATS GROUP: 1-0 DOSE: 75 MG/KG/DAY. - ANIMAL NUMBER OBSERVATION FIcReSTsmDAmYonmLaASsTs D_A_Y OBSERVED OBSERVED 657516 NO ABNORMALITIES DETECTED 657517 NO ABNORMALITIES DETECTED 657518 NO ABNORMALITIES DETECTED 657520 NO ABNORMALITIES DETECTED 657521 NO ABNORMALITIES DETECTED 657522 NO ABNORMALITIES DETECTED 657523 NO ABNORMALITIES DETECTED 657524 NO ABNORMALITIES DETECTED 657525 NO ABNORMALITIES DETECTED ~ 657526 AALLOOPPEECCIIAA BBOOTTHH FFRROONNTT LPEAGW((SS)) ALOPECIA RIGHT FRONT LEG(S) 657527 NO ABNORMALITIES DETECTED 657528 NO ABNORMALITIES DETECTED 657531 NO ABNORMALITIES DETECTED 657532 NO ABNORMALITIES DETECTED 657533 NO ABNORMALITIES DETECTED 657534 NO ABNORMALITIES DETECTED 657535 NO ABNORMALITIES DETECTED 00 11a 2 21 --_~ _-- CompanySanitized. Dossnotcontain TSCACBJ $2523 One Generation ReproducionStudy in Rats DuPones763 ~~ INDIVIDUAL CLINICAL OBSERVATToInOiNnSg AGNaDsTMAOTRITOANLITY DATA IN 7, FEMALE RATS Grove: vio Dose: 500 a/G/oAY am, NER osservarION CF1aRGtTEaSvDTDRIYON ASOSApYeTSERDvAEYD 67541 NO ABNORMALITIES DEFECTED 752 No ABNORMALITIES DETECTED 7563 NO ABNORGLITIES DETECTED 57504 ALOPECIA LEFT FRONT LESS) e735 Aavouroessccirna oormi FFRROONNTT LPEASN(S8)) 657506 NO ABORAALITISS DETECTED 67507 No AmORMALITIES DETECTED 6758 NO ANORMALITIES DETECTED -- e735 Aaoorseecciraa LLeeeenn FFRROONNTT LPEAGH(S5)) 657552 NO ABNORMALITIES DETECTED 657553 No AMORMLITIES DETECTED 657554 NO AmORMNTIES DETECTED 67555 No AmORMNLITIES DETECTED 657556 AALLOOPPEECCIIAA BBOoTAH FRROOVNET LPEAGW((SS)) 63755 NO ABNORMALITIES DETECTED 6755s AnuoorvBECCITA BBOOTTHH FFRROONNTT 1EA6H5(S)) - 657560 AALLOePsEcCIInA BBOoTmH FFRROONNTT LPENGH((SS)) .n 00 an a2 an 00 E1y o0 a2 77 ia --_ * Company Sanitized. Does n notcontain TSCA CBI 125231 OneGenerationReproductionSudy nats Duron --~ INDIVIDUAL CLINICAL OBSERVASToIROiNvSG AGNeDsTMAOTRITOANLITY DATA TN Py FEMALE RATS Group: vrz-o 20s: 3500 w/K/DAY -- avons, wovzeR osssuazzon _FSIcRhSTemmDmAYaaLoAnSwTseD_RnY ss757 to amvommwInIES DErsCrED ssses wo amonmLInIES DETECTED 6569 No amvomLIIES DETECTED 657570 0 amvonmuznaS bersCrED ss7s72 No AmwommLInIES DETECTED 67513 to amvonmuInIES DErCTED 6757 No AmoRMALITIES DETECTED 67575 aHuoorsssccinnn aRxeam LsBI0o(E6()S) ss7s76 auoveca som mow pas) --~ Rome mmo 6757 No AmiORMALITIES DETECTED 67578 No AmoRuALITIES DETECTED 657579 no amvommLITIES DETECTED 657560 vo amvommLirrss pEvECTED 701 no AmomGLITIES DETECTED ersez sons man 67563 vo amvonsuzmIES DEmECTED ssrses wo amvonmuIniEs DEmECTED 657565 NO ABNORMALITIES DETECTED 1i 2i 0 un : FS .2 | ~ ee eeCoempanySe aniizad. Dosnocontain TSCACI F-25231: OneGeneration Reproduction Study in Rats --_ DuPon.9763 -- APPENDIX N INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA INP, FEMALE RATS DURING LACTATION 25 Company Saniized. Doss not contain TSUA GBI 1.25231: One-Geneation Reproduction Study in Rats DuPon-9763 ~~ INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA IN P, FEMALE RATS DURING LACTATION EXPLANATORY NOTES Note Test days for animal fates are determined from the initiation of test substance administration. -- -- A-------- 26 -- t`eCmomrpaeny-- Seanietizeed.eDp oees neot crol nteaineTS--CA CBI 25231:OneGeneration ReproductionStodyinRass DuPo9763 --_ INDIVIDUAL CLINICAL OBSERVADTUIROINNSG ALNADCTMAOTRITOANLITY DATA IN 2, FEMALE RATS Grove: 11-0 DOSE: 0 MG/KG/DAY TT _FIcRSnTmDoAYv|oaLAnSsT DAY ANIMAL NUMBER opseRvATION OBSERVED OBSERVED 657451 NSOACARBINFOIRCMEADLIBTYIEDSESIDGENTETCETSETD DAY 121 657452 NSAOCRAIBFNIOCREMADLIBTYIEDSESDIEGTNECTTEESDT DAY 121 657493 NSAOCRAIBFNIOCREMADLIBYTIEDSESDIEGTNECTTEESDT DAY 121 657494 NSAOCRAIBFNIOCREMADLIBYTIEDSESDIEGTNETCETSETD DAY 123 657095 NSOACARBINFOIRCMEADLIBTYIEDSESDIEGTNETCETSETD DAY 123 657497 AALLOOPPEECCIIAA BROITGHHTFSRIODNET(SL)EG(S) --_ ASLAOCPREICFIIACERDIGBHYTDEFSRIOGNNT TLEEGS(TS)DAY 124 657498 NSOACARBINFOIRCMEADLIBTYIEDSESIDGENTETCETSETD DAY 123 657499 NSOACARBINFOIRCMEADLIBTYIEDSESIDGENTETCETSETD DAY 122 657500 NSOACRAIBFNIOCREMADLIBTYIEDSESIDGENTETCETSETD DAY 122 657501 ASLAOCPREICFIIACEDRIBGYHTDESISDIEG(NS)TEST DAY 123 657502 NSOACRAIBFNIOCREMADLIBYTIDEESSDIEGTNETCETSETD DAY 120 65750> 3 NSOACARBINFOIRCMEADLIBTYIEDSESIDGENTETCETSETD DAY 122 - 657504 NSAOCRAIBFNIOCREMADLIBTYIEDSESIDGENTECTTEESDT DAY 122 00 1241 2 21 1 -- TT Company Sanitzed. Doesnot contTSaCAiCnBI 1.25231: One-Geneation Reproduction Study in Rats DuPont9763 ~~ INDIVIDUAL CLINICAL OBSERVADTUIROINNSG ALNADCTMAOTRITOANLITY DATA IN P, FEMALE RATS GROUP: 11-0 DOSE: 0 MG/KG/DAY -- ANIMAL NOMBER ~ OBSERVATION FIRLSATCTDAATYION LDAASYTS DAY OBSERVED OBSERVED 657505 657506 657507 657508 657510 AALLOOPPEECCIIAA BROITGHHTFRFORONNTTPLAWE(GS()S) SACRIFICED BY DESIGN TEST DAY 123 ASLAOCPREICFIIACEBDOTBHY DFERSOINGTNBTAWE(SST) DAY 123 AALLOOPPEECCIIAA LBEOFTTH FFRROONNTT LLEEGG((SS)) ASALCORPIEFCIICAEDBOBTYH DFERSOINGTNBTAWE(SST) DAY 122 NSOACARBINFOIRCMEADLIBTYIEDSESIDGENTECTTEESDT DAY 121 NSOACARBINFOIRCMEADLIBTYIEDSESIDGENTECTTESETD DAY 126 0 27 21 70 21o 21 21 --~ --~ ----EJ-- eCeomnparneyreSfaensietiszeer p d.Doe esnoa t cons tain-- TSCACfa H25231:OneGeneration Reproduction Study in Rats Duo 9763 ~ INDIVIDUAL CLINICAL OBSERVADTUIROINNSG ALNADCTMAOTRITOANLITY DATA IN P, FEYALE RATS ANIMAL, NUMBER Grove: 19-0 DOSE: 75 MG/KG/DAY FIRLSATCTDAATYION LDAASYTS DAY OBSERVATION OBSERVED OBSERVED 657516 SNAOCARBINFOIRCMEADLIBTYIEDSESIDGENTETCETSETD DAY 120 657517 NSOACARBINFOIRCMEADLIBTYIEDSESIDGENTETCETSETD DAY 123 657518 NSOACARBINFOIRCMEADLIBTYIEDSESIDGENTETCETSETD DAY 122 657520 NSOACARBINFOIRCMEADLIBYTIEDSESDIEGTNECTTEESDT DAY 121 657521 NSOACARBINFOIRCMEADLIBTYIEDSESIDGENTETCETESDT DAY 123 657522 AALLOOPPEECCIIAA BROITGHHTFRFORNOTNT2ALWE(GS(S)) SACRIFICED BY DESIGN TEST DAY 123 ~ 657523 AALLOOPPEECCIIAA BBOOTTHH FFRROONNTT LPEAGN(SS)) SACRIFICED BY DESIGN TEST DAY 123 657520 NSAOCRAIBFNIOCREMADLIBYTIDEESSDIEGTNECTTEESDT DAY 125 657525 NSOACARBINFOICREMDALIBTYIDEESSIDEGTNETCETSETD DAY 121 657526 ASLAOCPREIFCIICAEDRIBGYHTDEFSRIOGNNT TLEEGS(TS)DAY 122 657527 NSOACARBINFOIRCMEADLIBTYIEDSESIDGENTETCETSETD DAY 120 657528 - SNAOCRAIBFNIOCREMDALI3TYIEDSESIDGENTETCETSETD DAY 121 657529 NSOACARBINFOIRCMEADLIBTYIEDSESIDGENTETCETSETD DAY 122 124 22 o0 221 1 - --_ 2% Company Sanilzed. Doesnotcontain TSCACB! 25231:OneGeneration Reproduction Study in Rats DuPont9763 ~~ INDIVIDUAL CLINICAL OBSERVA`TDIUROINNSG ALNADCTMAOTRITOANLITY DATA IN P; FEMALE RATS eeeeeeGrRoveP: eTV---0 --------DOSE--: --75 --MG/--KG/--DAY----LI --ACT--ATeIONtDAeYS e ANIMAL NUMBER OBSERVATION OFBISRESTRVDEADY OLBASSETRVDEADY - 657530 AALLOOPPEECCIIAA BBOOTTHH FFRROONNTT LPEAGW((SS)) 114 22 SACRIFICED BY DESTGN TEST DAY 123 657531 SNAOCRAIBFNIOCREMADLIBYTIDEESSIDGENTETCTEESDT DAY 127 657532 NSAOCRAIBFNIOCREMADLIBYTIEDSESDIEGTNECTTEESDT DAY 123 657533 SNAOCRAIBFNIOCREMADLIBYTIDEESSDIEGTNECTTEESDT DAY 121 657534 SNAOCRAIBFNIOCREMADLIBYTIEDSESDIEGTNECTTEESDT DAY 125 657535 NSOACARBINFOIRCMEADLIBYTIEDSESIDGENTETCETSETD DAY 123 --~ --~ --_--20------ Company Sanitized. Doesnotcontain TSCA CB) F-25231:One-Generation ReproductionStudy inRats DuPont9763 ~ INDIVIDUAL CLINICAL OBSERVADTUIROINNSG ALNADCTMAOTRITOANLITY DATA IN Py FEMALE RATS Grove: VI-0 DOSE: 500 MG/KG/DAY ANIMAL NUMBER OBSERVATION FIRTSATCTDAATYION LDAASYTS DAY OBSERVED OBSERVED 657541 NSOACRAIBFNIOCREMADLIBYTIDEESSIDGENTETCETSETD DAY 122 657542 NSOACRAIBFNIOCREMADLIBYTIEDSESIDGENTETCETSETD DAY 122 657543 NSAOCRAIBFNIOCREMADLIBYTIDEESSIDGENTECTTEESDT DAY 121 657548 AALLOOPPEECCIIAA RLIEGFHTTFRFORNOTNTLELGE(GS()S) SACRIFICED BY DESIGN TEST DAY 123 657545 AALLOOPPEECCIIAA BBOOTTHH FFRROONNTT PLAEWG((SS)) SACRIFICED BY DESIGN TEST DAY 120 --~ 657546 NSOACARBINFOIRCMEADLIBTYIDEESSDIEGTNETCETSETD DAY 122 657547 NSOACARBINFOIRCMEADLIBTYIDEESSDIEGTNETCETSETD DAY 123 657548 NSOACARBINFOIRCMEADLIBTYIDEESSIDGENTETCETSETD DAY 128 657549 AALLOOPPEECCIIAA LLEEFFTT FFRROONNTT LPEAGW((SS)) SACRIFICED BY DESIGN TEST DAY 121 657550 NSAOCRAIBFNIOCREMADLIBTYIEDSESIDGENTECTTEESDT DAY 125 657551 NSAOCRAIBFNIOCREMADLIBTYIEDSESIDGENTECTTBESDT DAY 122 657552 NSOACARBINFOIRCMEADLIBTYIDEESSDIEGTNECTTEESDT DAY 124 657553 NSOACARBINFOIRCMEADLIBTYIDEESSDIEGTNETCETSETD DAY 123 07 2o o 2211 0 11 . --~ 51 Company Sanitized.Doesnotcontain TSCACBI H-25231: OneGeneration Reproduction Study in Rats DuPont9763 ~~ INDIVIDUAL CLINICAL OBSERVADTUIROINNSG ALNADCTMAOTRITOANLITY DATA IN P; FEALE RATS GROUP: VI-0 DOSE: 500 MG/KG/DAY -- ANIMAL NUMBER OBSERVATION FIRLSATCTDAATYION LDAASYTS DAY OBSERVED OBSERVED 657554 657555 657556 657558 657559 657560 NSAOCRAIBFNIOCREMADLIBTYIEDSESIDGENTETCETSETD DAY 121 NSAOCRAIBFNIOCREMADLIBYTIEDSESTDGENTETCETSETD DAY 123 ASLAOCPREICFIIACEBDOTBHY FDREOSNITGNLETGE(SST) DAY 121 NSAOCARBINFOIRCMEADLIBTYIEDSESDTEGTNECTTEESDT DAY 121 NSOACARBINFOIRCMEADLIBTYIDEESSDIEGTNECTTEESDT DAY 130 AALLOOPPEECCIIAA BBOOTTHH FFRROONNTT PLEAGN((SS)) SACRIFICED BY DESIGN TEST DAY 122 2a 00 2211 -- 2 `Company Sanitized. Does not contain TSCA CBI F-25231: One-Generation Reproduction Study in Rats DuPont9763 ~ INDIVIDUAL CLINICAL OBSERVADTUIROINNSG ALNADCTMAOTRITOANLITY DATA IN Py FEMALE RATS GROUP: VITI-O0 DOSE: 3500 MG/KG/DAY. --_-- LACTATION DAYS ANIMAL NOMBER OBSERVATION FIRST DAY OBSERVED LOBASSETRVDEADY a 657566 NSOACRAIBFNIOCREMDALIBTYIDEESSIDGENTETCTEESDT DAY 122 657568 NSOACRAIBFNIOCREMDALIBTYIDEESSIDGENTETCETSETD DAY 120 657570 MSAASCSRIF1ICE2D.0BcYmDESCIHGENSTTEST DAY 122 1 1 657571 SNAOCRAIBFNIOCREMDALIBTYIDEESSIDGENTETCETESDT DAY 123 657572 SNAOCRAIBFNIOCREMDALIBTYIEDSESIDGENTETCETSETD DAY 121 657573 NSOACARBINFOICREMDALIBTYIEDSESIDGENTETCETESDT DAY 122 ~ 657574 NSOACARBINFOICREMDALIBTYIEDSESIDGENTETCTEESDT DAY 123 657576 AALLOOPPEECCIIAA BBOOTTHH FFRROONNTT LPEAGW((SS)) AALLOOPPEECCIIAA ACBHDEOSMTEN SACRIFICED BY DESIGN TEST DAY 121 00 2211 10 2211 657577 NSOACARBINFOICREMDALIBTYIEDSESIDGENTETCETSETD DAY 122 657579 SAALCORPIEFCIICAEDBOTBHY DFREOSNITGNPTAWE(SST) DAY 121 7 2 657580 SNAOCRAIBFNIOCREMDALIBTYIDEESSIDGENTETCETSETD DAY 122 657581 SNAOCRAIBFNIOCREMDALIBTYIDEESSDIEGTNECTTEESDT DAY 123 . 657583 SNAOCRAIBFNIOCREMADLIBTYIEDSESIDGENTETCETSETD DAY 121 5 Company Sanitized. Does not contain TSCACBI H-25231: OneGeneration Reproduction Study in Rats DuPont9763 ~ INDIVIDUAL CLINICAL OBSERVADTUIROINNSG ALNADCTMAOTRITOANLITY DATA IN P; FEMALE RATS GROUP: VIIT-0 DOSE: 3500 MG/KG/DAY ANIMAL NUMBER OBSERVATION FIRLSATCTDAATYION LDAASYTS DAY OBSERVED OBSERVED 657584 657585 NSOACARBINFOIRCMEADLIBTYIEDSESIDEGTNECTTEESDT DAY 125 ASLAOCPREIFCIICAEDBOBTYH DFERSOINGTNPATWE(SST)DAY 123 2 2 ~~ -- 54 CompanySanitized. Doss not contain TSCACBI