Document E7L9Ya4Q9J0R3g3qd7b4NERR

AR226-3162 DuPont-2932 TRADE SECRET Study Title H10-2-D40o4se3:OBrailoGpearvsaisgteenScteudSycrieneRniantgs Laboratory Project ID: DuPont-2932 Author: Carol Finlay, B.A. Study Completed on: August 29,2000 Performing Laboratory: E.I. du Pont de Nemours and Company HElakstkoenllRLoaabdo,rPa.tOor.yBfooxr T5o0xicology and Industrial Medicine Newark, Delaware 19714-0050 Work Request Number: Service Code Number: ,,ol contain TSCACB! Comp"y Sanitized.DoeS Page 1 o f93 H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2932 CERTIFICATION We, the undersigned, declare that this report provides an accurate evaluation of data obtained from this study. Reviewed bv: ^ ( SGe2nairoy--rWR^e.sJeeaprsco-hn-S-,cP-iLenDti.st z8 HutiooO Date Reviewed by: Vl3/fjfA CJutd(ith^G. Sftta\dDJleiZrre.c-cKtboiridXL, DL.AaJ>3 T. 2Z'Att6-2c>*>Z> Date Issued bv Study Director: (AVCAaStrotJalf,FfiSifc1laieyln,tB/isI'.tA.U, u(J -A<C<] 1t>0 Date Conti'Petty O o not cntain TSca Cbi -2- H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2932 % TABLE OF CONTENTS Page CERTIFICATION........................................................ LIST OF TABLES........................................................ LIST OF FIGURES...................................................... LIST OF APPENDICES.............................................. STUDY INFORMATION............................................. STUDY PERSONNEL.................................................. SUMMARY..................................................................... INTRODUCTION......................................................... MATERIALS AND METHODS................................. BA.. TTeesstt SSupbecstiaens.c.e...a..n..d...P...o..s.i.t.i..v..e...C..o..n...t.r.o..l...................................... C. Animal Husbandry.............................................. 321... IFHdeoeeundstiianfnigcdaEWtniovanitre..or...n....m......e....n....t........................................................................................................................................................... ED.. Q4S.tuuadAryanniDmtieanlseHigaennal.dt.h..P.M.r..oe.n.t.ei.t.os..rt.i..n....g....P....r...o...g....r..a...m................................................................................ F. Assignment to Groups and Study Start............... G. Dosing Material Preparation and Administration 21.. PToessittiSvuebCstoanntcreo..l.s......................................................................................................................... H. B3.odNyeWgateivieghCtosn..t.r.o..l.s........................................................................................................... I. Mortality and Clinical Observations.................... KJ.. TCroelaletmcteionnt oanf dFlAuonrailnyesiDs aotfaB..l..o..o..d...a..n.d...L...i.v..e..r..s............. RESAU. LInT-SLiAfeNTDoxDiIcSoCloUgyS.S..I..O...N............................................................................ B. Fluorine Data.............................................. :.......... 321... TPFoaecssitttoSirvsuebICnstfoalunnectrneoc..li.sn...g......I....n....t..e....r..p....r...e....t..a....t..i...o....n......o....f....A......n.....a....l...y....s....i..s............................................ CONCLUSIONS...................................... RECORDS AND SAMPLE STORAGE TABLES.................................................... CBIcontain t sc a ...4 ...4 ...4 ...5 ...7 ...8 ...9 ......999 10 ..10 .10 .10 .111110 1111 ..1112 .1122 12 1132 1144 14 14 1155 15 16 17 -3 - H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats FIGURES....... APPENDICES DuPont-2932 LIST OF TABLES Page 1. MEAN BODY WEIGHTS................................................................................................................................... j g 2. MEAN BODY WEIGHT GAINS........................................................................................................... 20 3. MEAN BLOOD FLUORINE LEVELS............................................................................................................... 21 4. MEAN BLOOD FLUORINE CONCENTRATION NORMALIZED TO DOSE............................................ 22 LIST OF FIGURES Page 1. MEAN BODY WEIGHTS.........................................................................................................................................24 2. MICROMOLAR EQUIVALENTS IN RAT BLOOD..............................................................................................25 3. MICROMOLAR EQUIVALENTS IN TEST COMPOUND AND POSITIVE CONTROLS.............................27 LIST OF APPENDICES Page A. INDIVIDUAL BODY WEIGHTS........................................................................................................................... 29 B. INDIVIDUAL CLINICAL OBSERVATIONS........................................................................................................ 71 C. INDIVIDUAL FLUORINE LEVELS................................................................ Companysanlfbed. De*nof coniato TSCACB/ -4- H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats STUDY INFORMATION TEST SUBSTANCE: Substance Tested: ( Svnonvms/Codes: H-24043 Haskell Number: 24043 Composition: Known Impurities: Not supplied by the sponsor POSITIVE CONTROL: Substance Tested: Synonvms/Codes: H-24019 Haskell Number: 24019 DuPont-2932 J rsc4 CBl 5- - H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats STUDY INFORMATION (Continued) DuPont-2932 POSITIVE CONTROL: Haskell Number: 24020 Composition: Known Impurities: Unknown Sponsor: E. I. du Pont de Nemours and Company UW.Sil.mAi.ngton, Delaware 19898 Study Irutiated/Completed: April 30, 1999 / (see report cover page) In-LifeInitiated/Completed: July 11, 1999/October 12, 1999 c topany Sanitize 6- - ~ e* *** TSCA CBj H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats STUDY PERSONNEL Study Director: Carol Finlay, B.A. PrimarMy Tanecahgnemicieannt:: RJuidchitahrdC.P.SMtadaltehre,nPah.D., D.A.B.T. Blood Fluorine Data Analysis: Gary W. Jepson, Ph.D. Management: Matthew S. Bogdanfiy, Ph.D., D.A.B.T. Toxicology Report Preparation: Wanda F. Dinbokowitz > Laboratory Veterinarian: Wanda L. West, D.V.M., A.C.L.A.M. DuPont-2932 Convoli; omiiIimiui llul OOiiMlill Cttl H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2932 SUMMARY gTahveaogbej.eJcotibveeaobfstohribsesdtuadnydwtoasactocuemvaulluaateteinthaempoatmenmtiaalliafnorsHys-t2e4m0.43S,ixwghreonuapdsmoifn5ismteareled by aCdrml:CinDiste(SreDd)ItoGSonBeRgrroautspeoafc5h rwatesrefogriv5ecnon10se0cmutgiv/kegd/adyasy aonfdHt-o2450g4r3o.upTshfeotre1st0sduabysst.ance was Afropmprothxeim5a-dteolsye2ghroouupr.s aOftnersethleectfeirdstddaoysse(,5b,lo1o0d,1w3a,2s4c,o5ll1e/c5t2ed, 9f4ro)m5 rthatesoprebritgarlosuipnuwseoref each rat reeuctohradneizdeodnaenadcthhdeabylooofddoansidnglivaenrds twheenreacpoplrleocxtiemd.ateBlyodeyvewreyigohthtserawndeecklindiucrailngsigthnesrweceorevery dpaneesdrico2rdibp.eodAsidftiodvrietHioc-on2na4lt0lryo4,l3s3., Hne-g2a4t0iv1e9c(o1n0trmogls/,kdge/dioanyi)zaenddwHa-te2r4,0c2o0m(2o0ilm, agn/dkgc/odmay)o,ilw/aecreetotensete(d80a:s20),' No deaths occurred during the study. No compound-related clinical signs of toxicity were ddouibarsriernrhgveeathd, esiandloitvhsaeintirgoantps,edraioloosdpe.edcRwiaai,ttshbldtahocesketdoescwtulsiatuhrbdHstia-s2cn4hc0ea,r2gH0e-,e2xa4nh0di4bs3itt.eadiRnwiantegst dopoefsrveiandreiwuomuitshapHnadr-t2sd4io0arf1rt9hheeeaxbdhouidbryiitnegd odthielei/oadncoeizstioendngewpnaeetrgeioradtai.vnedActlhooenpteprcooislairtwaivtasesecoxobhnsitberroitvlesed,dHndo-u2rc4iln0ing1i9cthaaelnsrdiegcHnos-v2de4ru0yr2ipn0eg.ritTohdheeisntcuordamyts. odiol saenddwcoitmh pcToohmseitpmivaereaacbnolebnottrodoyltshw.eeCdigeoihmotnspiaazrneiddsomwnaeotaefnrbbaoondddyycwwoemeigigohhitlst ngbeaegitnwasteioveenf tcthhoeenrtraraottslssddaoonssededdhwiwgihitthehrHHth--2a24n400t4h43e3Hwa-ne2rde4t0h2e0 tdchoifamftetrhoeienlr/ceaecweatatossntaueddnyieffgsetaarteritvnaecnecdoinnthtaregoeelxaopnnedcteHtes-td2dr4aa0yte119obpfeobtsowidteiyevnwe ctehoigenhtrrtaotgsla.rianAt,sciwtcoaapuspncetoianmrgspftlhoicartathttehedeabmgyeetahnebfoacdty owiel/iagchettsoannednmegeaatnivbeocdoyntwroelisghatngdaeinqsuaolfttohoerragtrseadtoesretdhawnitthheHH-2-420440319ispcoosmitipvaeracobnletrtoolst.he com adAnodsstinenaogdrwmy-iastlhtiazt1ee0df0ofmor rfglfu/lkuogorirHnine-2el4ecv0oe4nl3ste.innAt wfnohraortelheaebutlenosdotedsruwtbhasestacnnuocrteveaacn(hediseetviamecdhatdpeudorsitinotigivne1f0icnocitnoytn)rsowel.causTtichvaeelcdualyasteodf vAaUluCeIsNoFf/5D66fo,4r7t9h.e1falunodri7n0e,7c8o9m.6pofonrenHt-o24f H01-924a0n4d3Hw-2as402230,2,9re8s.6peacsticvoemlyp. ared to AUCINF/D wDU10eonrscdeeoe-anrapstdhepjceurouscxttoeiivdnmedaaidrtteaeioyalynsss2ure5onsxfdutelahtrneitsddhse3itnuxcdumtyhrov,edeaAed(rUAmatCUienICiaNsIbtNFrsa/oFDtri/poDftnoi)oorfnotfhratehnpedtoestrseiettstitsevusnebutcisbootsanntnatocnroefc.lefsl,,uHHor--i22n44e00i41n39t,hateondbmlHoaol-e2d.4ra0t2s0f,'or Company Sanitized. not contain TSCACBi -8- H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2932 INTRODUCTION The objective of this study was to define the potential ofH-24043 to be absorbed and to pmbrieobvalcioocouudsmlayunlsdahtloeiwviennr.atomTbhaiemoatmecscatulsimaunbuslsatyatsentceinemwm, aaassmicmnodamilcspa.atereddbtyoa2npaloystiitciavledceotnertrmolinsathtiaotnwoefrteomtalatfelurioarlisne Tafhteeri5nidtiaaylsd.oTsahgeemcheoansebnofdoyr wtheeigsthutdoyfwthaesr5a0ts0amftger/k5g/ddaayys. oHf odwoseivnegrw, daossdinegcrweaassedtebrmyi7n%ated compared to the mean body weight on the first day of dosing. The dosage of 500 mg/kg/day was ddcohososeesddenwwbiiatthhseHtdh-eo2nt4e0st4ht 3esurebexssputaelntrsiceeonfcforeardn5agnecfooinnvsdeeircnauglltismvtueedadinaeysb.soaIdntyatwhdeeaiifgliyhrstdtgoraasinanggeoeffoi2nf9d3i0gn0rgammstugs.d/kyTg, .h5eTrachtoesnrwtaroetsrle r5garrtosauthspawdalesaronehodavodesreaadnllwomviteeharanHll-b2mo4de0ya4nw3befoiogdrhy5twlcooesinsgshoetcfug1ta9iivngeroadfma2ys9s. agtraamdsa.ilyIndtohseagseecoofn7d5r0anmgge/fkingd.inTghsetsuedy,' sTthuedideos.saTgheeodfo1s0a0gemog/fk3g0/0damygw/kags/cdhaoyswenasbraespeedaotendt.heFirveesurlattssodfo2seaddwdiittihonHa-l2r4an04ge3fifnord-ing 65 gcoranmsesc.uFtiivveedraaytsswatearedaolssaogdeoosfed30w0itmhgH/k-2g4/d0a4y3hfaodr a5ncoovnesreaclultmiveeadnabyosdayt awdeoigshatgegaoinf of g1r0o0ump gh/akdg/adnaoy.veTrahlelsmeeraantsbeoxdpyerwieenicgehdt gaaninovoefr2al5l bgroadmysw. eight gain of 16 grams. The control stAhuloplspbelleoamnoadelnystsaaemlsr.pelpReoserwst.uelrtse farnoamlyaznedalyfosrestootaflsefllueoctreindelicvoenrtesanmt. pTlehsiswriellpobertpcroensteanitnesdthine aresults of MATERIALS AND METHODS A. Test Substance and Positive Control The test substance, H-24043, was supplied by the sponsor as a light amber brown liquid. The epsuvobisdsitetianvnceceecooafnnitdnrospltsao,bsHiitlii-tv2ye4, 0cso1un9chtraoanlsdsaHapc-hp2ae4na0rg2ee0d,intwoceboreelossrtuaopbrplpeliheuydnsdbiceyarltthhseteastcepo,onwndsaiotsirooanbsssweorhfvitehtdee.ssotuliddys.. NThoe test B. Test Species Male Crl:CD(SD)IGS BR rats were received from Charles River Laboratories, Inc Raleigh North Carolina. The Crl:CD(SD)IGS BR rat was selected on the basis of extensive experience Company Sanitized. Does not contain TSCA CBI -9- H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2932 winictihdethnicsesotrfasinpoanntdanitesosuusitdaibseilaitsyesw. ith respect to longevity, hardiness, sensitivity, and low C. Animal Husbandry 1. Housing Environment ARantismwalerreoohmousswederseinmgalyinitnaisntaeidnolenssansteaeplp, rwoxiriem-matees1h2c-ahgoeusr sluigshpte/dnadrekd caybcolve e(fclaugoerebsocaerndtsl.ight) oanudtsiadteattheemapcecreaptuterde roafn2g3esw1erCe manidnoarraenladtidviedhnuomt iadfifteyctotfh5e0stud1y0.%. Occasional exclusions 2. Feed and Water nRTuaotpdriewtnioatntLeaarlbwrDeaqiseutpirreo5mv0ie0dn2etdschaanoddwli.tboiTtbuhemef.freeAeedlolifrsasgtpsuewacriefairneetdefeecddonbPtyaMmthIieNnamuntatrsin.tuiofnacItnutreerrntaotimoneaelt, sIpnce.ciCfieerdtified 3. Identification aePasasrsscioiihggrnnrtaemotd.eatnsTosthietgeoancigmnhrfeoronaurttpm.tsoa, tagionroniunopdnsiv,thiedeauccahalgriaedtelwanbtaiefsliscteaimtnicoplnourdnaeurdmilytbheiedreuwnntaiiqsfuimeeda6rb-kydeicdgaiotgreHtiaadstetkoneotlielfdiacnoaitnmiotanhl.entAuamifltbeorefr 4. Animal Health Monitoring Program tAfhosollssoepwethicnaigftiewpdrooiucnledtdhbueereHesaxasprkeeecpltleeLdrfaotboromirmaetdpoaprcyetratihnoeidmiscacalilelhnyetatioflitchasiasnnutderegertnihtvyaitroocfnotmnhteeanmsttuainldaymn:tonleivtoerlisnagreprboeglroawm, the aWndatoerthsearmcpolnetsamarienaanntasl.yzed for total bacterial counts, and the presence of coliforms, lead, Feed samples are analyzed for total bacterial, spore and fungal counts. bSyamthpelecsagfreowmasfhreerssh.ly washed cages and cage racks are analyzed to ensure adequate sanitation rsCepeqeructiiiffriieeemddehannetiasmvayanldmfneeetoadtlstio,s auefsxleacdteo,exdgiunsa,tarcathenldtoemreidnaaxbtiyemdtuhhmeymdcraoonncuacrefbancotrtnuastr,ieoarnntsodomofregkeaetnysocppoehncotiafsipmehdianntaeunstt.rsi,tTiiohnnecalul ding pwroeuseldncneotobfetheexsepeccotnedtamtoiinmanptascbt ethloewinttheegrmityaxoimf tuhme sctuodnyc.entration stated by the manufacturer Tlahbeoraantiomryalanhiemalathl vaentdereinnavriiraonn.mental monitoring program is administered by the attending Company Sanitized. Does not contain TSCA CBI -10- H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats Quarantine and Pretest DuPont-2932 scfUiolgiprnno6iscnadoalaflmyyislvla.npaeTplsahaster,eHirnnaatjtussskriwyge,nlelsorLeroaawfbbdeoniirsogaerhtamoesrdaeyl,3obtrtheiihemnajrevuasirtosydr.wu. rTeinrhegertrehametsopwvreeetdreesftroopbmeserirsovhdeipdapndidnagielyxcaafmrotroinnmesodarndtadaliilqtyyuafaornardnatninyed On the bases of acceptable body weight gains and freedom from clinically apparent signs of disease or injury, the rats were released from quarantine by the laboratory animal veterinarian E. Study Design Substance NegDCatoeimvioenoCiizloendtrWolaster Com oil:acetone PosiHHti--v22e440C021o09ntrols Test Substance Vehicle Not applicable ComCooiml: aocieltone Dosage (mg/kg) 0 00 2100 Number of Animals 30 3300 30 30 H-24043 None 100 30 Assignment to Groups and Study Start After the quarantine period, the rats were selected on the bases of adequate body weight gain, freedom from any clinical signs of disease or injury, and a body weight within 20% of the m5 reaatns., sTohtehastetlhecetreedwraetrse wnoersetadtiivstiidceadllbyysicgonmifpicuatnetridziefdfe, rsetnracteifsieadmroanngdogmroiuzpatbioondyinwtoei6ghgtromuepasnos.f naAgufemteabrteatrhssweigatinsmmmeeaonrtfktdeodosgoirnrogtua.pttsDo,ooeesadicnhognrbatethgweaantasoihlnootufesesetadcdhianyrdai1tv..idTuhaellrya.tsTwheerleasbte3twdeigenits7oafntdhe9awneimekasl of sRaactrsiftihcaetdwbeyrecanrobtoansdsiigonxeiddetoastphheysxtiuadtiyown earnedrdeliesacsaerddefdorwoitthhoerutlapbaothraotloorgyicpaulrpevoaselusa,toiornw. ere G. Dosing Material Preparation and Administration 1. Test Substance H-24043 was mixed with deionized water so an accurate volume could be delivered. The daomsoinugntaondf ttehset sduobssintagnmceixetaucrhercaotnrceecnetirvaetdiown.asTbhaeseradtsonwethree bdoodseydwaetiaghvtocluomlleecotefd1omnLe/a1c0h0dgayoof f ______________________________ ____________________________________ Company San d ed . Doe* -11 - re ta in TSCA CBI H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2932 pbroodcyedwuerieghtot.mTahinetadionsihnogmmoigxetnuereityw.as stirred on a magnetic stir plate throughout the dosing 2. Positive Controls The solid positive control compounds were suspended as emulsions in their respective vehicles. rbCeeocfemoirveoeisdluwwspaaessnubdsaiensdegdaitsointnhtechoevmebhooidcilyl.ewfToehrigeHhr-ta2tci4oo0l1loe9fc.atecIdettowonnaeseatnocehcceodsmasyaoroyifltdwooadssiins2sg0o:al8vn0ed.HthT-e2h4esu0as2mp0eoinunsniatocneeatochnerat hscuoosmnpcoeegnnestrinoaetniitsoynw..erTehsetidrroesde ovnolaummeasgndeidticnosttierxpclaeteedth1rmouLg/h1o0u0tgthoefdboosdiyngwperiogchet.duTrheetodomsainingtain 3. Negative Controls Deionized water was chosen as a negative control because it was the vehicle for the test swcsuuoebbmrssettoaathnnikeccaeevc.oeehtrCoipconolmees.sitoTifviolhereatcnshoedenrctparotoosmslswit.oievirkeeacdcoeontsoternodelisn(.8a0E:sa2ec0ph)anrwaetegeraertoicvohemocsoefrnnotamrosltnhreaegtrarateitvcseedivocoesedndtr1owmlsitLhbeotchfaecuotsemesttohielyor H. Body Weights Adullrirnagtsthweerreecwoveeigryhepderoionde.ach day of dosing. The rats were weighed weekly or every other week I. Mortality and Clinical Observations waCmaasgoeni-ngsdirtiavetisedxuwaaemlrlyeinhcaoatinnoddnlusecdttoeaddneadtteelcxetaamsmtoionrniebcduefndodarioalyrbndthoerraomduarglahtbsoeuahtnatdvhieaobrsntauondrdmy.aaplApbteeaehrvaaevnricyoerw. aenigdhainpgp,eaeraacnhcerat J. Collection and Analysis of Blood and Livers tAhpeporrobxitimalastienluys2ohfoeuarcsharfatterfrtohme fGirrsot udposIe., A1-t2amll Lothoefrbsloeloedctwedasticmoellepcotiendtsi,n5toraEtDs/gTrAoutpubweesrferom ceoultlheacnteizdedacbcyorcdairnbgotnodtihoexfidoelloawneinstghescsihaedanudlees:xs^nguination, and the blood and livers were Company Sanitized. Does not contain TSCA CBI - 12- H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2932 Group I I n m IV V VI r Dosing Days 1-5 1-5 1-10 1-10 1-10 1-10 1-10 BTliososdue Collected Blood and Liver Blood and Liver Blood and Liver Blood and Liver Blood and Liver Blood and Liver | Test day 1 (2 hSouamrspploinsgt dToismineg) Tleesstt ddaayy 510at(2sahcoruifriscepo(2sthdoousrisngp)ost TTeesstt ddaayy 2143 TTeesstt ddaayy 9541/52 dosing) Five to 10 mL of blood was collected into EDTA tubes at sacrifice. The livers were weighed. paTnahacelkybazgleoedoddfaofnrrdotomsthaailplflplureaodtrsrinewfera.isgererafrtiegdetroatJeadcaknsdonthLealbiovreartsowrye,rDe efreopzwena.terT,hNeebwloJoedrsweyaswahpeprreoiptrwiaatesly The total fluorine content of the blood samples was determined using a Wickbold torch bcolomobduwstaisondemceotmhopdo,sefodlloorwveodlabtiyliaznedalyinsitshwe pitrhesaefnlcueoroidfewieotnosxeylgeecntivaendelsewcteropdt eth. roTuhgehliaqnuiodxyaqyuderooguesnabflsaomrbeining asoclluotsieodn qaunadrtaznaalpypzaerdatuussi.ngThaeflcuoomribduesitoionnspelreocdtuivcetsewleecrterocdoel.leTctheed ainnaalyntical dflautoar(inpepmbioFpienrseiastcehncsaem. ple) was supplied to Haskell Laboratory personnel for evaluation of K. Treatment of Fluorine Data HN-o2n4c0o4m3pbayrtmuseinngtalWainnaNlyosnisliwn aVsecrosinodnu3ct.e0dsoofntwbaloroed(PfhluaorrsiingehtdCatoarpd,erMivoeudnftraoinmVraietswd,oCsAed).with tAdWimaUtianeCNfoIiNolfendFsloii(snnciconslongufcdetewixnntatgrrraaeaptripooerlanaotvuxeinddtdietmeodreiat)nhmfreienecpiaurtyenr.svseeoTn(fthAsceoUthmmCeapIaxNuritemFian)u,gumCnddmeoerbairvsxteehardevnpebdhdltoaecorromdmnacicncoeoannlkctrhieanantelitftori-ancltiifpwoeanar(saTcmCui/rm2ev)t.eearxfTsrhofremomthe (concentration). The points included in determination of the terminal half-life were selected manually and given in units of time. Since the dosages and fluorine content for each positive control and the test material varied, all doses were normalized to 0.1 mmole/kg for comparative pwuerrpeocsaelsc.ulTahteedaacncdumreuploartitoedn binudtenxo(tAfuI,rtlh/e(rl-ues-ekdt).) and bioaccumulation index (BI, Cmax x Ai) cHo-n2t4ro0l1s9, bauntdbHec-2a4us0e20ofwvearreiaubsielidtyasanpdosliitmivietecdosnetnrosiltsi.viDtyoosifntghedialnuaelnyttsicwalermeeutsheodd,asthneegative bdeatcekcgtiroonu,nadnwyavsalsueetsatli0st.e2dpapsmlefslsuothrianne.0.2Sipnpcme 0w.2eprepmexcwluasdethdefrfolumorfiudrethceorntcreenattmraetinotn. limit of uTsheedpaesrcperonvt iodfefdluboyritnheeasnpdonmsoorl.ecTuhlaermweeaigsuhtreomfethnetsteresstuslutibnsgtafnrcoemanandaplyossiistivoef tcootanltrbollosowdere uorine were used as received (ppm F) from Jackson Laboratory. Fluoride ion was converted to Company Sanitized. Does not contain TSCA CBf 13 H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2932 dmeisccrroimptoiolanrs (o/xfMda)teaqmuiavnailpeunltastioofnaacntidveprceosmenptoantieonnt aforer pfurortvhiedrecdoimnpAapripseonndsi.xTCh.e data and RESULTS AND DISCUSSION A. (ITna-Lbliefes T1-o2x, iFciogluorgey1, Appendices A-B) No deaths occurred during the study. No compound-related clinical signs of toxicity were oddtddohieuuibleai/rrsoariidenrnncrhogegivezstetoaiethnhd,dnegeseiwanrdpnelaeoitecvhtrsgoeiaeioravntdritegaoia.rvnntpysed,Oepdcratneihooloreoensidpoertp.readdooct.RslwidaiarAtoi,aittsvshtlbesoelddtpaehoccexweoskcheniitidoatetbhrcsowiwtutHleaslisdat-us,h2rbHno4dHsob0-ti2a-ss4c2cen43l4hrci0vn0aee1eir,2x9cgdHh0aeaidl-,ebn2usxaid4irtnhgei0Hndind4bgs-s3ia2tttd.lea4houdi0epRnr2wieiran0necteg.gcistaotdopThvaoefhenesrverdiesyantdcaurepoindwuoemoymurit.itshohoaedpinHrladiare-nt2nxdsr4dhiaoa0itcbrfs1roit9htdhmeeoeedasxbeadhoduisdborwyiirtnieetghd The mean body weights and mean body weight gains of the rats dosed with H-24043 were tcpchoooammstittpiohvaeirelra/eacbcowleentatotsronoaletshd.neiefCdfgeeaoritmeoivnnpeciazecreioidsnnowtanrgoaoetlefaorbnnaodntdedHys-ctw2ode4mai0yg1oh19itlsbpneboeteswgtiwateiteveivneeentchcotehonenrtratrortasolt.lsrsaTdtasohnswidesadhdsiiwgfcfhioetemhrreHpnthlc-iae2cna4rt0etehs4due3lbHtaey-nd2tdh4inet0h2fea0ct wdieffigerhetntcheasnitnhemceoamn booidl/yacweteoignhetnseognattievset dcaoynt1ro. lTahnedHH--2244004139rpaotssiwtiveerecyoonutrnoglerratasn.dYlioguhntegreirn wcwaaonneendiiimtggrthhhoattellssgaetaaexinxapndpessecleorotqiewfeudtnaehcrlreaetrtoraaeatoteposretfdhrgbioarooensddaeyytdoeowfrwurteniahtigphageinhdHrtta-bhg2noea4idimH0ny4,a-w23list4e.ia0sipgA1cph9ocetcmpagoroapsusiannitrtht.iaiavnbtOegltelchdfoteoeonrrmtttrahheoneealisnmca.ogbameolsddoayiifrlwfe/eaeerceixegnpthcoetencsteaeatdnnsedttgoumadgtyeiavaisenntabrot dy B. Fluorine Data (Tables 3-4, Figures 2-3, Appendix C) 1. Factors Influencing Interpretation of Analysis The data used in the kinetic analysis were derived from a limited screen, and therefore several tacoraevbe(lo1ao)tsdaa, sn(i3dn)gcsloetnedasoiddsyee-rswattaaitosenumssaaeyrdenaionmtdphkoairvntaeentbitce.seAnmaaccyohuoiperlvemedoa,yf acnnoodnts(bi4de)eltrihaneteioasran,ms(2op)lfepthsaeirztkiecinuiselatliorcwismaappnopdrltymanoacnyely AimpppaecntdcixalcCu.lation of the terminal half-life. A more complete list of considerations is shown in Company Sanitized. Does not contain TSCA CBI 14 H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats 2. Positive Controls DuPont-2932 rTahteblpooosditicvoenctionnuterdoltsowriesreetHhr-o2u4g0h1o9uatnthdeHd-o2s4i0n2g0p.erTihoed Han-d24m01ay9 nnootrmhaavliezreedacjlhMedeqstueiavdayle-snttastein h(Failgf-ulirfee2oAf)4.0T.5hdeaCysm. aTxhfeorHH-2-244001199AwIawsa9s8599.8.05and11th6e.9B0Ipwpmas(5M83ea8n2..2.STDh)ewHit-h24a0te2r0minal normalized /M equivalents in rat blood peaked after 5 days of dosing and then decreased throughout the dosing period (Figure 2B). The Cmax for H-24020 was 518.12 44.89 ppm (Mean SD) with a terminal half-life of 8.3 days. The H-24020 AI was 12.5 and the BI was s6t4u9d7y.,5w. iFthoronealychfooufrtohef tphoesmitiovceccuornritnroglps,obstl-odoodsew. aTs hsaemsmplaeldl saatmsepvleensitzime eanpdoianntaslythtircoaulghout the pvuarrpiaobsielist.y Tshhoeutlodtableintatekrennailnetxopaocscuoruenrtewsuhlteinngusfirnogmthaendoermrivaelidzetedrmdoinsealwhaaslfd-leisfcerfiboerdcobmyparative HTAh-U2eC4A0IN2U0FC./IDNFan/Dd wfoarsththeefbluaosrisinfeocrocmompopnaerinstown abset5w6e6e,4n7p9o.1sitfiovreHc-o2n4tr0o1l9s aanndd t7h0e'7te8s9t'6mfaoterrial. 3. Test Substance pT1e5hr.e3io1Hdp-a2pn4md04m(3ManyeonarnomtahlSaizvDeed)rweraiMtchheeaqdtuesirvtmeaalidenyna-tlsshtiaantlefr-a(lFtifibegluoorofed226cC.o3)n.dtianTyuhse.edCBtomloraoixsdefwotharrsHosu-a2gm4h0op4ule3tdtwhaeatssdeo1vs0ei1nn.g07 lstiuifzneeefaopnrodcinoatmnsaptlhyarrtoiacutaigvlhevoapuruitratpbhoielsiestystu.sdhTyo,huweldiHthb-2eo4nt0al4ky3efnoAuinIrtwoofaastch3ceo8mu.4notacnwcduhrterhnineugBspiInowgstat-shdeo3s8de7e.9ri.Tv1e.hdeTtshemrematloilntsaaallmhpallfe bcinoatsmeirspnofaonlreencxotpmoofspuHarr-ei2sr4oe0ns4ub3letitwnwgaesefr2no3mH,2-9a284n.0o64ram3saaclniodzmepdpoadsrioetsidveetwocaAosnUdtrCeosIlcNsr.FibT/eDhdevbAayluUAeCUsIoCNfIFN5/6DF6/D,f4o7ra9nt.hd1ewafnlaudsotrhinee s7h0o,7w8n9.i6n fAoprpHe-n2d4i0x1C9.and H-24020, respectively. The data, calculations and equations are CONCLUSIONS Rats dosed for 10 consecutive days with the test substance, H-24043, exhibited no mortality or bwtelesotiogsdhutwbgsatasainnncsoett-haraectlhawiteeevdreecdclifonomircpaHal-rs2ai4bg0lne4s3toodftuthoreixnnigceigtthyaetaivnlOedrchdoaandytrmdoolesarianntgsb.opdAeryisowtdee.aidgyhtsstaatnedfomrefalunobroindeyin the dUanydserretshueltceodnidnitmioondseorafttehaisbsstourdpyti,oandamnidnirsettreantitoionnooffHfl-u2o4r0i4n3e itno tmhealbeloraotds.foDro1s0e-caodnjsuescteudtivaereas 2u5nxdearntdhe3xcutrhveeA(AUUCCININF/FD/Df)orfothrepotessittisvuebcsotanntcroel.s, H-24019 and H-24020, were approximately Company Sanitized. Do* notcontain TSCA CB1 - 15- H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2932 RECORDS AND SAMPLE STORAGE Specimens (if applicable), raw data, and the final report will be retained at Haskell Laboratory, Newark, Delaware, or at Iron Mountain Records Management, Wilmington, Delaware. * Company Sanitized. D ou not contain TSCA CBI -16- H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2932 TABLES CompanySanded. Ooe, contain Ts c a CB( - 17- H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2932 m TABLE 1 MEAN BODY WEIGHTS (g) DTaeysst 1 23 645 987 222111540830 332327 433194 4476 5512 666555120543 766487 D'3232222e22W2225919678i54432o28307839a0926n........t6.36.1.2.631ie3088zredNegaCt23222222i222o2v9887655342m-15e511690419.......1...C92.928314O48oinl trolsCA33333333322o5c5433221099m_e01594614997t........o7.7.2.2905O3466niel: 419- .4 378.7 350.5 378.3 _ 430619..08 -_ 400.7 _ - __ 449- .5 407.8 - 411.4 _ 463- .5 434.5 _ _ - 454.9 _ -_ 469.7 511.0 464.7 527.6 -_ 528- .0 487.0 - - 505.1 - 547.7 . _ 558- .0 515.4 _ _ . _ _ Positive Controls H-24019 229911..55 333321100972488.....51763 333321119878....1934 H-24020 222432272...054 225428..49 222222887665938939......195838 338579..97 334101..93 393.9 - 416- .9 _ 402.9 - 425.0 -438.1 438.2 465- .6 -- - 45-2.3 52-3.4 465.8 - - 470.9 Test Substance H-24043 222225543318652.....39330 222876437...094 232299172...370 337595..12 388.6 423.2 - 455.8 448769..57 - 515.2 - 536.7 _ - 9 Company Sanitand. Oon, not contain TSCA CBI - 18- H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2932 . TABLE 1 (Continued) MEAN BODY WEIGHTS (g) DTaeysst DeWioantiezredNegaCtiovme COoinl trolsCAocmetoOniel: 8706 -- -. 53.9.0 8812 57-3.0 -. . 88 589.5 - . 9940 58-4.6 556566..29 556672..82 Indicates the animal was not weighed. Positive Controls H5-26430.419 570.7 - 585- .3 597.9 H-24020 - 499.2 - 55328-7..78 Test Substance H-24043 575.8 - 650808..20 - 606.7 Company Saniti zed. Doe* not contain TSCACB/ H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2932 TABLE 2 MEAN BODY WEIGHT GAINS (g) DTaeysst 1-5 11100---121034 101-05-19/452 D211eW82i7731o611125an......t314353iezredNegaCt2i1ov728662re1a85269..C....O081425oinl troOlsi2l1:1C4A725-695431oc......1me39109tone Positive Controls H-24019 2177..14 1611990...202 279.0 H-2244.0920 21558541765.....87024 Test Substance H-24043 6256..46 2128713..764 309.0 Company Sanitized. Dees not contain TSCA CBI H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2932 TABLE 3 MEAN BLOOD FLUORINE LEVELS Negative Controls Positive Controls Test Substance DTaeysts 115130 DeW(ipopanmtiez)red <<<<0000....2222 C(opmpmO)il <<<0000.2...222a (0.1) CAo(cpmeptmoOn)iel: <<0000....3226aC((00..16))b H-24019 H-24020 ___466_4812....(1587PPm(1)(((_0277_....8669_))))__ ___2675_6214(....P6672Pm(((1()763_1..._.8224_))))__ H(-p2p4m04)3 151..94((10..68)) 155..74 ((02..73)) 512/452 <00..22e <00.3.2a (0.1) <00..22d 4226..29 ((22..86)) 100..59 ((03..20)) 42..32 ((00..27)) 94 0.9C 0.3a (0.1) <0.2 13.2 0.2C (0.1) 0.8 (0.2) a Mean of4 of the 5 values. One of the values was below the level of detection (LOD). bcd MOStenaaenndvaoarlfdu3ed.oefvFtiohauteiro5onvfiatshluienevsp.aalruTeewnstohweoesfreesth.beelvoawluethsewLeOreDb.elow the LOD. e Mean of 2 of the 5 values. Three of the values were below the LOD. Company Sanft/*. nof contain TSCa CBI -21 - H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2932 TABLE 4 MEAN BLONOODRMFLAULOIZREINDETCOODNOCSEENTRATION DTaeysts M Positive FHE-2q4u0i1v9alents ControlHs -24020 M F Equivalents 1 25911524340 74278..9692 ((21731.3.5)a) 994859..8855 ((4131.65.)9) 641149155...353848 (((443022...695))) 58198..2182 ((2434..49)) 31979141...034155 (((258262...187))) 40..6244 ((10..14)) a Standard deviation is in parentheses. Test Substance M FHE-2q4u0i4v3alents 137307461....75403370 ((11((5405....1563)))) 21743...022770 (((411...532))) ComPanys, -22- CBi'" ' la in t s Ca H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2932 FIGURES Company Sanftlzed. D*not ^nfarn TSCA CBf -23- H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats_________ 400 -, % FIGURE 1 MEAN BODY WEIGHTS (g) # DuPont-2932 -0-- Negative Control (Deionized Water) G --Negative Control (Corn Oil) A--Negative Control (Corn Oil:Acetone) X-- Positive Control H-24019 9K--Positive Control H-24020 Q-- T est S ubstance H-24043 12 -24- TSCA CBI H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2932 FIGURE 2 MICROMOLAR EQUIVALENTS IN RAT BLOOD A . N o r m a l i z e d R a t Blood H- 240O19r aftlMG aEvqaugiev a l e n t s Res ul t i ng f rom a 10-Day eMxipcorsoumreo.laVr (ajliuMes) aerqeuimveaalennstsanodf Her-r2o4r0b1a9rs(paroesisttiavnedcaorndtrdoelv)iaintiorant.blood resulting from a 10-day oral gavage B. N o r m a l i z e d R a t Blood H- 240O20r a/ilMG aEvqaugiev a l e n t s Res ul t i ng f rom a 10-Day Mexipcorsoumreo.laVr (a/lxuMes) aerqeuimvaealennstsanodf Her-r2o4r0b2a0rs(paroesisttiavnedcaorndtrdoelv)iaintiorant.blood resulting from a 10-day oral gavage Company Sanitized. O o not contain H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2932 C. N o r m a l i z e d R a t Blood H- 240O43r a lft MG aEv aqguei v a l e n t s Re s ul t i ng f rom a 10-Day Mexipcorsoumreo.laVr (a/lruMes) aerqeuimvaealennstsanodf Her-r2o4r0b4a3rs(taersetsstuabnsdtaarndced)eviniartaiotnb.lood resulting from a 10-day oral gavage 0 Com ply Sam/uud. Does "o* contain TSCACBI -26- % H10--2D40o4se3:OBrailoGpearvsaisgteenScteudSycrieneRniantsg % FIGURE 3 MICROMOLAR EQUIVALENTS IN TEST COMPOUND AND POSITIVE CONTROLS DuPont-2932 Company Sanitized. Oom not 5s3oor' to o>o CO -27- H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2932 ^ APPENDICES 0 Company m u m . 0099 not contain TSCA CBI -28- H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2932 APPENDIX A Individual Body Weights Co'"W "i' Sm W M 40(iet " '" "nTSCACB, -29- H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats INDIVIDUAL BODY WEIGHTS ABBREVIATIONS: SD - sacrificed by design EXPLANATORY NOTES DuPont-2932 C '" P a n ,s .,, ,, ilK tD M s not contain tsca CBI -30- H10-2-D40o4se3:OBrailoGpearvsaisgteenScteudSycrieneRniantsg ANIMAL NUMBER 632649 632650 632651 632652 632653 DAY 1 208.8 223.3 238.6 243.4 210.5 DAY 2 208.2 231.1 243.1 240.0 210.5 DEIONIZED WATER (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP I TEST DAYS DAY 3 DAY 4 DAY 5 219.8 239.3 253.6 253.0 217.6 225.1 243.7 260.8 257.3 223.0 240.4 261.7 276.7 272.4 236.0 SD test day 5 SD test day 5 SD test day 5 SD test day 5 SD test day 5 Oo3 a 1vt o%tO3o flftt (>o0 roa -31- # DuPont-2932 ji H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER .DAY 1 632654 632655 632656 632657 632658 210.1 234.4 236.4 251.5 220.8 DAY 2 217.0 238.1 243.5 255.0 227.5 % DEIONIZED WATER (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP II TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 227.9 248.1 250.2 265.0 235.1 236.0 258.7 258.0 277.0 240.8 248.5 265.7 261.9 292.0 249.3 259.9 278.0 272.2 297.3 256.7 270.6 289.3 280.3 308.0 264.1 ANIMAL NUMBER 632654 632655 632656 632657 632658 DAY 8 DAY 9 282.8 295.4 286.5 317.0 274.3 286.6 307.1 286.1 324.3 278.2 TEST DAYS DAY 10 303.1 315.8 294.5 329.6 286.0 SD test day 10 SD test day 10 SD test day 10 SD test day 10 SD test day 10 10 3Oo303-U)t> o o -32OB # DuPont-2932 H10-2-D40o4se3:OBrailoGpearvsaisgteenScteudSycrieneRniantsg ANIMAL NUMBER . Day 1 632659 632660 632661 632662 632663 199.9 232.6 238.1 248.1 219.4 Day 2 208.0 238.9 243.1 255.5 227.9 DEIONIZED WATER (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP III TEST DAYS Day 3 Day 4 Day 5 Day 6 Day 7 211.0 240.7 247.4 261.5 229.9 220.9 251.8 258.1 269.7 241.7 231.0 260.8 265.7 279.8 249.9 238.9 268.0 273.5 286.2 257.7 247.8 275.7 285.0 292.8 265.2 ANIMAL NUMBER 632659 632660 632661 632662 632663 Oo33<o Day 8 Day 9 254.1 279.4 291.8 297.0 272.0 - 261.5 286.1 302.4 302.4 276.4 TEST DAYS Day 10 Day 13 270.0 296.3 304.5 309.2 285.1 293.1 309.1 334.9 331.1 299.9 SD test day 13 SD test day 13 SD test day 13 SD test day 13 SD test day 13 Sanitized. Does 3OO o t3--o>ao4- -3 3 OB 0 DuPont-2932 % H10-2-D40o4se3:OBrailoGpearvsaisgteenScteudSycrieneRniantsg__________________________________________ DEIONIZED WATER (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP IV ANIMAL NUMBER Day 1 Day 2 TEST DAYS Day 3 Day 4 Day 5 Day 6 Day 7 632664 632665 632666 632667 632668 208.2 228.3 245.8 254.3 218.7 213.9 236.6 251.0 262.3 226.8 219.9 244.9 263.4 272.0 238.5 226.1 252.4 273.8 285.6 249.3 236.6 264.0 282.8 293.6 260.3 242.9 274.3 297.4 300.6 270.1 252.6 282.1 310.0 315.2 282.0 ANIMAL NUMBER 632664 632665 632666 632667 632668 Day 8 256.0 288.0 314.6 319.9 291.6 Day 9 262.8 297.9 326.9 330.0 301.7 TEST DAYS Day 10 Day 13 273.2 306.5 334.0 342.1 314.7 _a _a __a _a Day 18 318.2 367.1 398.1 414.4 385.7 Day 24 349.0 408.5 441.8 460.4 437.5 SD test day 24 SD test day 24 SD test day 24 SD test day 24 SD test day 24 # DuPont-2932 \ i 1 a Rats not weighed. -34- Ooeso*cont H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER Day 1 Day 2 % - DEIONIZED WATER (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS TEST DAYS Day 3 Day 4 GROUP V Day 5 Day 6 Day 7 632669 632670 632671 632672 632673 194.4 224.5 226.8 256.3 217.3 197.8 228.6 230.9 267.1 224.8 202.5 237.4 237.2 272.4 230.8 209.5 246.7 243.5 281.3 241.3 215.1 251.9 249.0 295.1 248.2 221.4 259.9 256.9 304.6 258.6 228.1 268.8 262.0 315.4 265.7 ANIMAL NUMBER 632669 632670 632671 632672 632673 Day 8 234.3 271.0 268.0 319.4 268.9 Day 9 232.6 271.0 273.6 328.4 276.4 TEST DAYS Day 10 Day 13 239.6 280.9 276.0 334.8 285.2 _a --a _a _a _a Day 18 278.1 328.3 308.4 389.8 . 335.6 Day 24 _a _a _a _a _a Day 25 301.2 361.5 346.2 441.1 370.8 ANIMAL NUMBER 632669 632670 632671 632672 632673 Day 32 Day 39 TEST DAYS Day 46 Day 52 322.8 389.9 378.5 377.5 400.9 355.5 415.7 421.9 517.0 433.8 366.6 434.9 434.6 542.7 457.3 392.4 449.1 456.4 566.6 484.2 SD test day 52 SD test day 52 SD test day 52 SD test day 52 SD test day 52 a Rats not weighed. P(o0T -35- # DuPont-2932 H10--2D40o4se3:OBrailoGpearvsaisgteenScteudSycrieneRniantsg_____________________________________ DEIONIZED WATER (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS ANIMAL NUMBER Day 1 Day 2 TEST DAYS Day 3 Day 4 GROUP VI Day 5 Day 6 Day 7 632674 632675 632676 632677 632678 197.0 228.8 238.3 238.1 211.3 205.1 239.3 243.2 240.7 227.6 214.1 243.1 252.0 248.2 233.9 221.7 255.3 259.8 255.9 244.4 232.7 264.9 270.3 261.7 253.6 242.0 271.8 280.9 276.0 262.6 250.9 278.0 289.4 282.0 266.0 ANIMAL NUMBER 632674 632675 632676 632677 632678 Day 8 261.7 285.7 294.1 289.0 278.3 Day 9 TEST DAYS Day 10 Day 13 - 266.0 291.6 300.3 298.0 286.3 . 276.7 296.7 309.8 302.7 291.4 _a _a _a _a _a Day 18 336.2 352.9 368.3 356.9 351.4 Day 24 _a _a _a _a _a Day 25 380.4 389.6 411.3 397.5 387.6 Company Sanit*, os ANIMAL NUMBER 632674 632675 632676 632677 632678 Day 32 Day 39 TEST DAYS Day 46 Day 52 Day 53 Day 60 Day 67 419.5 433.4 441.0 423.9 419.3 465.7 482.3 484.3 458.8 460.1 471.8 485.0 502.4 472.8 467.2 508.2 536.0 530.2 492.8 487.8 529.6 540.7 552.8 514.7 502.0 545.8 584.8 565.0 525.1 518.0 566.2 592.2 571.8 536.4 523.5 5S3onoa' a Rats not weighed. oV) -36- DuPont-2932 B H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER 632674 632675 632676 632677 632678 Day 74 581.9 612.8 587.0 544.2 539.3 Day 81 _a _a _a _a _a # DEIONIZED WATER (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP VI TEST DAYS Day 88 Day 94 583.5 645.4 605.1 562.0 551.6 548.9 652.9 603.2 569.4 548.5 SD test day 94 SD test day 94 SD test day 94 SD test day 94 SD test day 94 # DuPont-2932 ty oe* not contain TSCACBI a Rats not weighed. -37- H10--2D40o4se3:OBrailoGpearvsaisgteenScteudSycrieneRniantsg_______________________________________________________________________________________________ DuPont-2932 CORN OIL (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP I ANIMAL NUMBER DAY 1 DAY 2 TEST DAYS DAY 3 DAY 4 DAY 5 627789 627801 627805 627810 627818 222.6 215.9 249.4 230.5 229.7 220.7 209.1 250.1 231.6 228.6 223.5 223.5 263.3 241.9 239.1 236.9 233.5 273.6 254.4 252.4 247.7 240.1 283.7 265.0 260.2 SD test day 5 SD test day 5 SD test day 5 SD test day 5 SD test day 5 < ? I ! I I HI eo00 - 3 8 - # ## H10-2-D40o4se3:OBrailoGpearvsaisgteenScteudSycrineeRniantsg________________________________________________________________________________________________ DuPont-2932 CORN OIL (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP II ANIMAL NUMBER DAY 1 DAY 2 TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 627793 627797 627799 627800 627808 214.8 239.9 228.9 246.9 235.6 224.4 245.9 231.4 252.8 241.6 232.1 257.3 242.3 265.2 250.1 243.1 267.5 246.2 279.3 262.1 249.9 280.7 258.9 283.6 270.4 257.0 288.0 261.5 295.5 284.1 262.0 290.9 266.4 300.1 287.4 ANIMAL NUMBER DAY 8 DAY 9 TEST DAYS DAY 10 627793 627797 627799 627800 627808 270.6 303.9 280.2 312.0 303.6 274.9 305.1 284.3 315.4 305.7 283.5 324.2 294.7 331.3 321.8 SD test day 10 SD test day 10 SD test day 10 SD test day 10 SD test day 10 Company Sanitized, sB5voo>1>>' -39 - a H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats_______ ___________ ANIMAL NUMBER DAY 1 DAY 2 CORN OIL (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP III TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 627796 627806 627807 627809 627816 239.8 227.3 221.5 234.2 235.0 249.7 234.2 225.9 240.4 238.6 253.6 239.4 237.1 252.5 250.0 252.5 242.9 244.1 260.3 258.9 267.7 258.5 254.9 272.8 265.1 277.2 270.4 257.7 277.9 274.5 289.8 275.2 260.3 282.6 278.6 ANIMAL NUMBER DAY 8 DAY 9 TEST DAYS DAY 10 DAY 13 627796 627806 627807 627809 627816 O To3f3iJ) 285.9 282.8 270.7 297.9 291.8 290.1 285.8 274.7 300.2 296.4 300.0 302.8 280.7 311.9 305.7 322.7 320.3 305.2 336.2 330.2 SD test day 13 SD test day 13 SD test day 13 SD test day 13 SD test day 13 Sanitised. Does 3OO o3f3-tiO>o)BotJ - 4 0 - # DuPont-2932 H10--2D40o4se3:OrBailoGpearvsaisgteenScteudSycrieneRniantsg ANIMAL NUMBER DAY 1 DAY 2 CORN OIL (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP IV TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 627791 627794 627804 627812 627817 231.1 224.4 224.7 221.9 233.5 235.4 233.0 228.8 231.5 231.3 241.2 238.1 230.6 236.3 229.0 246.8 247.8 243.0 245.7 244.8 255.9 260.0 251.7 255.5 255.4 262.6 267.4 252.9 264.9 266.4 268.4 270.1 259.5 269.5 270.0 ANIMAL NUMBER 627791 627794 627804 627812 627817 DAY 8 274.0 286.1 267.2 278.2 277.8 DAY 9 279.1 289.5 270.6 282.7 280.4 TEST DAYS DAY 10 DAY 13 285.0 295.4 278.1 294.3 294.6 _a _a _a _a _a DAY 20 334.4 377.4 345.8 356.5 368.7 DAY 24 365.6 416.7 378.1 388.4 407.3 SD test day 24 SD test day 24 SD test day 24 SD test day 24 SD test day 24 DuPont-2932 Company SanRtaed !m3 _3a------------------ af^ats not weighed. *VoC)O -41 - S a n it iz e d . Does not contain TSC H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 CORN OIL (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP V TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 627792 627798 627813 627814 627815 235.8 241.1 214.8 217.5 230.1 240.8 253.4 219.2 220.5 242.2 244.3 257.6 220.5 223.7 243.8 247..9 266..1 233 .2 225..2 255..7 252.5 272.9 239.8 233.8 265.0 264.4 281.9 243.2. 236.7 270.0 268.1 286.2 246.8 240.6 274.1 ANIMAL NUMBER 627792 627798 627813 627814 627815 o o 3 ANIMAL NUMBER *< 627792 627798 627813 627814 627815 DAY 8 282.4 294.3 258.7 248.0 289.2 DAY 9 286.4 296.3 259.2 250.7 293.4 TEST DAYS DAY 10 DAY p.3 295.2 315.7 267.9 257.3 303.3 _a _a _a _a __a DAY 20 360.0 380.2 323.6 299.3 368.3 DAY 24 389.2 403.5 342.3 319.4 396.5 DAY 34 426.1 443.1 367.9 343.7 434.9 DAY 41 DAY 47 TEST DAYS DAY 52 456.5 470.7 395.0 358.7 462.6 482.3 496.9 407.2 372.7 487.3 496.8 517.3 416.8 386.9 505.9 SD test day 52 SD test day 52 SD test day 52 SD test day 52 SD test day 52 a Rats not weighed. DuPont-2932 H10-2-D40o4se3:OrBailoGpearvsaisgteenScteudSycrieneRniantsg ANIMAL NUMBER DAY 1 DAY 2 CORN OIL (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP VI TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 627795 627811 627819 627820 627821 218.0 228.6 248.8 225.5 227.5 219.5 226.3 255.3 228.9 233.2 225.3 236.7 264.9 239.2 240.7 234.3 246.1 274.4 247.9 246.1 239.4 251.5 280.4 255.6 251.2 246.2 259.6 288.0 261.3 259.8 250.1 263.6 290.3 265.3 263.9 ANIMAL NUMBER DAY 8 DAY 9 TEST DAYS DAY 10 DAY 13 DAY 20 DAY 24 DAY 34 627795 627811 627819 627820 627821 O 261.4 273 .0 304.5 281.3 272.6 JIMAL gMBER 3 to 27795 7811 S27819 (>27820 S27821 DAY 41 384.2 422.0 505.9 478.0 411.8 o3o asr sgrjRats not weighed. 2 265.0 276.7 308.0 282.9 275.3 DAY 47 398.0 439.3 534.9 504.1 426.1 270.7 285.6 324.3 292.4 281.8 -a -a 308.0 337.8 399.7 367.2 330.1 TEST DAYS DAY 52 DAY 55 _a _a _a _a _a 411.1 455.4 551.7 529.7 439.1 DAY 61 435.7 463.0 574.4 547.1 459.0 -43- 329.8 360.6 431.2 393.0 352.9 DAY 68 440.7 473.6 588.6 558.6 463.3 362.0 396.4 472.5 445.5 385.6 DuPont-2932 m H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 90 DAY 94 CORN OIL (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP VI TEST DAYS 627795 627811 627819 627820 627821 474.6 503.6 638.1 608.6 509.0 485.0 511.6 653.1 618.0 521.5 SD test day 94 SD test day 94 SD test day 94 SD test day 94 SD test day 94 # DuPont-2932 Dom noicontain -44- H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats_________ _________________________________________________ ANIMAL NUMBER DAY 1 DAY 2 CORN OIL:ACETONE (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP I TEST DAYS DAY 3 DAY 4 DAY 5 625361 625363 625364 625380 625383 322.6 273.7 291.1 289.4 304.7 325.0 271.4 290.9 286.2 299.7 337.6 278.4 299.9 291.5 302.7 340.3 281.7 306.0 300.1 310.7 349.7 286.7 312.0 305.5 313.1 SD test day 5 SD test day 5 SD test day 5 SD test day 5 SD test day 5 O T(30a<3o3at OoQN. o1o3SaT T>otoT w -45- DuPont-2932 H10-2-D40o4se3:OBrailoGpearvsaisgteenScteudSycrieneRniantsg ANIMAL NUMBER DAY 1 DAY 2 CORN OIL:ACETONE (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP II TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 625355 625362 625367 625368 625378 280.0 290.3 301.5 312.3 309.6 282.0 294.1 307.8 318.0 306.4 293.0 303.5 315.6 326.0 327.3 297.9 308.9 320.1 336.4 328.4 306.1 313.8 327.7 343.7 333.7 311.2 315.8 333.7 347.5 336.6 315.7 323.8 345.6 360.8 346.9 ANIMAL NUMBER DAY 8 DAY 9 TEST DAYS DAY 10 625355 625362 625367 625368 625378 321.7 323.9 349.1 364.2 350.1 320.9 332.3 352.4 380.8 354.2 333.6 332.9 363.8 386.7 365.4 SD test day 10 SD test day 10 SD test day 10 SD test day 10 SD test day 10 DuPont-2932 Company Sanitized. Does oo3a5HCCO'trO'i- - 4 6 - DO % H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats_____________________________ % CORN OIL:ACETONE (NEGATIVE Control) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS ANIMAL NUMBER DAY 1 DAY 2 GROUP III TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 625357 625358 625370 625384 625385 311.9 285.7 307.9 294.2 297.6 308.8 286.3 316.7 300.0 304.6 320.3 295.5 329.5 312.0 313.0 328.4 296.4 337.9 309.3 320.4 340.5 306.0 346.9 316.3 331.9 343.3 302.7 349.8. 314.1 334.0 361.1 309.2 364.1 321.4 345.4 ANIMAL NUMBER DAY 8 DAY 9 TEST DAYS DAY 10 DAY 13 625357 625358 625370 625384 625385 364.2 319 .-8 373.4 325.6 347.0 370.3 321.6 374.7 331.0 349.5 376.9 320.3 385.6 340.6 358.9 405.6 340.7 407.0 357.1 377.6 SD test day 13 SD test day 13 SD test day 13 SD test day 13 SD test day 13 \ -47- # DuPont-2932 % H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 % CORN OIL:ACETONE (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP IV TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 625354 625365 625371 625376 625381 303.0 327.7 294.5 289.7 297.8 304.1 328.7 299.0 289.9 297.5 310.5 337.9 313.4 302.2 301.7 312.2 343.6 318.3 304.9 305.6 319.3 357.7 321.8 313.2 314.4 324.7 357.2 329.6 317.0 314.4 331.2 364.3 338.5 322.8 321.0 ANIMAL NUMBER DAY 8 DAY 9 TEST DAYS DAY 10 DAY 13 DAY 20 DAY 24 625354 625365 625371 625376 625381 336.2 370.5 340.3 331.5 321.6 337.0 379.3 345.9 339.0 329.1 348.8 381.2 351.2 345.2 331.6 355.8 407.1 372.6 363.2 341.2 377.7 438.2 413.0 399.7 358.2 396.1 459.6 447.3 432.9 381.8 SD test day 24 SD test day 24 SD test day 24 SD test day 24 SD test day 24 0 DuPont-2932 KudttioO 1 I l%2. a9. > S -48- * H10-2-D40o4se3:OBrailoGpearvsaisgteenScteudSycrieneRniantsg______ __________ % ANIMAL NUMBER DAY 1 DAY 2 CORN OIL:ACETONE (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP V TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 625356 625359 625360 625372 625374 291.7 297.9 296.8 294.8 295.9 291.2 303.3 300.7 298.8 302.2 304.5 314.0 308.5 310.6 312.1 307.0 315.0 312.7 317.4 321.7 316.9 323.5 319.1 324.0 323.4 319.8 323.5 332.2 329.0 328.3 323.9 333.9 339.5 335.6 337.2 ANIMAL NUMBER 625356 625359 625360 625372 625374 Oo3o3>o ANIMAL NUMBER 625356 625359 625360 625372 625374 DAY 8 328.8 339.1 347.9 344.7 338.0 DAY 9 334.7 346.2 354.3 348.8 344.6 TEST DAYS DAY 10 DAY 13 341.3 353.6 363.4 355.1 350.8 361.9 372.9 381.7 373.1 371.5 DAY 20 396.7 410.0 419.8 395.1 401.3 DAY 24 _a __a _a _a _a DAY 27 431.3 440.9 465.9 432.1 447.2 DAY 34 466.2 467.7 484.1 454.7 466.8 DAY 52 TEST DAYS 533.7 530.3 555.4 506.2 512.3 SD test day 52 SD test day 52 SD test day 52 SD test day 52 SD test day 52 Sanitized. Dees not contain TSCA BI a Rats not weighed. -49- # DuPont-2932 Company Sanitized. Does H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 CORN OIL:ACETONE (NEGATIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP VI TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 625353 625369 625373 625375 625377 305.9 281.7 294.6 289.1 293.9 307.3 279.9 301.3 291.0 294.8 316.8 289.7 312.7 298.0 302.9 325.0 286.9 317.0 307.0 312.0 331.7 292.8 325.4 309.6 318.0 330.1 295.3 329.0 314.2 317.4 342.5 303.8 334.6 323.5 325.0 ANIMAL NUMBER 625353 625369 625373 625375 625377 DAY 8 344.7 307 .3 340.6 324.7 325.0 DAY 9 352.7 311.9 348.2 336.0 333.7 TEST DAYS DAY 10 DAY 13 358.1 317.2 352.6 336.9 340.7 371.7 331.1 371.5 350.1 353.5 DAY 20 399.1 347.6 402.3 387.9 376.3 DAY 24 _a _a _a _a _a DAY 27 427.7 374.9 444.6 432.3 405.2 ANIMAL NUMBER 625353 625369 625373 625375 625377 DAY 34 453.3 388.2 477.1 455.6 419.1 DAY 52 _a _a _a _a _a TEST DAYS DAY 76 DAY 90 DAY 94 544.9 483.8 628.8 567.3 470.3 562.8 505.3 661.3 589.8 492.0 565.3 514.8 673.7 588.8 496.6 SD test day 94 SD test day 94 SD test day 94 SD test day 94 SD test day 94 3Oo3 a Rats not weighed. DuPont-2932 H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 w H-24019 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP I TEST DAYS DAY 3 DAY 4 DAY 5 625322 625323 625336 625343 625349 290.3 285.0 316.5 288.2 303.6 283.7 285.5 313.5 281.9 295.9 291.5 290.2 320.1 286.8 308.2 298.9 290.9 327.1 291.0 310.1 298.0 294.0 329.0 293.7 318.1 SD test day 5 SD test day 5 SD test day 5 SD test day 5 SD test day 5 ( DuPont-2932 ,0M"Q T*UIWgXuBdiuo -51 - H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats____________________ H-24019 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS ANIMAL NUMBER DAY 1 DAY 2 GROUP II TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 625320 625330 625332 625341 625350 279.3 286.7 300.0 304.9 257.1 283.0 286.1 295.9 309.0 268.5 287.7 291.1 304.1 317.5 267.3 288.4 296.5 308.8 320.0 272.2 295.9 304.0 315.0 325.1 272.6 299.4 302.3 322.4 327.5 276.3 300.6 306.7 320.7 327.4 283.6 ANIMAL NUMBER DAY 8 DAY 9 TEST DAYS DAY 10 625320 625330 625332 625341 625350 308.5 314.0 324.1 332.4 279.8 306.3 312.6 321.8 320.3 282.5 312.1 310.1 318.3 325.6 284.3 SD test day 10 SD test day 10 SD test day 10 SD test day 10 SD test day 10 DuPont-2932 nf confab TSCA C B f -52- contain TSCACBl m H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H-24019 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP III TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 625321 625327 625342 625345 625348 307.0 311.4 273.7 291.2 265.5 307.8 306.6 275.5 291.7 258.6 311.4 312.5 282.3 297.3 268.0 319.6 317.8 285.8 303.3 275.2 322.3 318.3 290.8 306.4 280.1 328.4 319.3 294.2 310.4 285.2 335.2 327.6 326.6 316.1 290.6 ANIMAL NUMBER DAY 8 DAY 9 TEST DAYS DAY 10 DAY 13 625321 625327 625342 625345 625348 337.8 334.3 304.3 317.3 302.7 339.6 337.0 305.9 312.9 306.5 346.1 336.3 307.8 315.0 309.7 371.2 355.3 324.4 336.9 336.4 SD test day 13 SD test day 13 SD test day 13 SD test day 13 SD test day 13 a.0N O9s -53- DuPont-2932 m H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H-24019 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP IV TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 625325 625328 625338 625340 625352 282.8 315.6 264.6 304.0 285.5 285.9 315.2 261.9 309.2 283.9 291.7 323.9 268.5 316.9 289.1 295.5 327.7 272.6 326.0 299.6 303.2 335.0 275.7 329.8 307.9 309.2 340.4 281.9 334.1 308.2 308.3 340.1 284.4 338.4 312.4 ANIMAL NUMBER DAY 8 DAY 9 TEST DAYS DAY 10 DAY 13 DAY 20 DAY 24 625325 625328 625338 625340 625352 318.6 352.0 287.4 347.0 316.9 321.9 351.7 291.3 352.2 322.3 327.4 357.5 290.2 359.2 321.0 331.6 367.4 291.1 368.1 329.6 355.8 400.2 320.4 389.3 355.7 381.3 423.9 339.9 419.0 375.3 SD test day 24 SD test day 24 SD test day 24 SD test day 24 SD test day 24 m DuPont-2932 Company Sanitized. Dee* not contain TSCA CBI -54- Company San iti*** Does t> H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H-24019 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP V TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 625324 625329 625333 625334 625344 303.0 318.9 292.4 274.6 262.9 298.5 316.3 291.2 277.0 262.2 305.8 326.5 297.8 286.4 269.0 312.1 335.4 304.1 290.6 273.5 320.1 338.3 307.7 292.0 274.5 322.8 346.7 312.0 300.1 284.1 326.8 351.6 313.5 304.2 - ANIMAL NUMBER 625324 625329 625333 625334 625344 DAY 8 332.5 352.5 315.8 292.6 280.7 DAY 9 337.9 360.1 316.7 302.2 285.2 TEST DAYS DAY 10 DAY 13 336.1 357.0 319.3 305.8 289.3 299.6 364.3 325.8 312.0 295.8 DAY 20 336.0 396.4 349.2 338.6 309.7 DAY 24 _a _a _a _a ___a DAY 27 380.3 423.3 375.2 368.8 330.4 ANIMAL NUMBER . DAY 34 DAY 52 TEST DAYS 625324 397.3 625329 442.7 625333 384.6 625334 384.2 3OOo3K5. 625344 348.3 (o>/> a Rats not weighed. oBJ 447.4 498.1 427.4 426.5 391.0 SD test day 52 SD test day 52 SD test day 52 SD test day 52 SD test day 52 -55- DuPont-2932 H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H-24019 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP VI TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 # DuPont-2932 625326 625335 625346 625347 625351 313.2 301.0 290.2 266.0 310.6 317.1 303.6 293.4 275.6 310.9 325.5 302.3 300.2 287.7 321.1 330.9 310.4 309.5 300.0 329.6 336.2 315.1 313.5 308.5 338.2 336.0 299.6 318.6 316.6 341.6 293.6 326.0 326.9 340.7 ANIMAL NUMBER 625326 625335 625346 625347 625351 DAY 8 311.5 294.-2 292.9 330.5 351.1 DAY 9 308.9 285.3 290.8 330.1 357.8 TEST DAYS DAY 10 DAY 13 297.5 274.0 288.4 333.0 350.5 274.2 266.3 296.9 355.7 380.0 DAY 20 335.4 340.1 352.5 402.1 413.7 DAY 24 _a _a _a _a DAY 27 390.7 393.8 388.2 436.2 452.4 Company D oSanitized. ANIMAL NUMBER DAY 34 625326 625335 625346 625347 625351 427.5 427.0 407.4 466.4 483.3 3O 33a5H(O>oo>A'o a Rats not weighed. DAY 52 _a _a _a __a _a TEST DAYS DAY 62 DAY 76 DAY 80 497.5 506.0 485.8 568.6 559.0 540.0 538.6 523.7 617.8 596.8 547.9 547.7 532.8 618.1 607.2 -56- DAY 90 565.2 562.1 542.4 632.6 624.0 DAY 94 577.5 579.5 556.9 638.9 636.8 SD test day 94 SD test day 94 SD test day 94 SD test day 94 SD test day 94 H-24043: Biopersistence Screening IQ-Dose Oral Gavage Study in Rats______________ m ANIMAL NUMBER DAY 1 DAY 2 H-24020 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP I TEST DAYS DAY 3 DAY 4 DAY 5 627756 627767 627771 627773 627777 227.2 227.0 219.5 246.8 225.4 226.4 231.8 214.7 244.4 221.4 233.4 237.9 226.1 252.7 232.9 238.6 245.8 233.5 263.8 239.4 237.5 248.6 239.6 262.3 236.0 SD test day 5 SD test day 5 SD test day 5 SD test day 5 SD test day 5 O To303(S<33N)nfpOl>l. o not contato TSCA CB! -57- DuPont-2932 % H10-2-D40o4se3:OBrailoGpearvsaisgteenScteudSycrineeRnaintsg______ _____________ % ANIMAL NUMBER DAY 1 DAY 2 H-24020 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP II TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 627768 627774 627776 627782 627785 236.9 258.6 212.0 221.6 220.3 244.1 261.6 216.3 228.3 221.7 245.2 275.8 223.7 237.3 234.7 256.5 283.4 226.6 239.0 238.4 256.2 289.3 229.6 238.8 241.8 265.5 301.5 233.7 244.7 250.5 271.4 303.2 236.9 246.7 255.6 ANIMAL NUMBER DAY 8 DAY 9 TEST DAYS DAY 10 627768 627774 627776 627782 627785 O I tn %oo-% 272.3 319.-8 246.1 251.0 260.7 291.9 326.3 252.3 264.0 268.5 293.5 338.2 254.4 268.2 267.9 SD test day 10 SD test day 10 SD test day 10 SD test day 10 SD test day 10 \ -0A -58- # DuPont-2932 *udu0 H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 m H-24020 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP III TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 627758 627763 627764 627787 627788 235.1 212.1 230.0 235.1 219.4 240.3 218.3 235.0 241.0 222.3 248.6 226.5 246.1 250.1 232.2 255.8 234.3 251.3 257.2 239.6 261.2 230.8 254.8 258.6 247.6 272.0 235.5 261.7. 237.6 256.7 276.1 238.0 264.7 240.3 257.9 ANIMAL NUMBER DAY 8 DAY 9 TEST DAYS DAY 10 DAY 13 627758 627763 627764 627787 627788 280.6 255.-2 275.8 221.7 274.1 283.6 261.2 281.9 235.7 276.9 295.8 272.5 288.0 234.7 284.8 308.7 285.8 306.7 234.9 309.4 SD test day 13 SD test day 13 SD test day 13 SD test day 13 SD test day 13 (5ft. %ao%.3Ooo3 3T.ofto -59- m DuPont-2932 H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H-24020 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP IV TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 627759 627761 627770 627779 627786 226.6 240.7 235.6 231.5 211.6 232.9 247.4 244.3 237.9 218.2 241.4 257.1 253.6 252.6 222.5 250.9 262.5 260.1 261.4 230.4 254.2 266.7 267.7 262.3 230.6 262.1 259.2 277.3 273.8 240.6 265.4 262.6 279.8 277.5 244.1 ANIMAL NUMBER 627759 627761 627770 627779 627786 DAY 8 277.8 240.1 291.4 289.0 251.3 DAY 9 284.9 257.4 301.3 293.4 255.8 TEST DAYS DAY 10 DAY 13 288.0 266.9 306.4 301.0 257.0 _a _a _a __a _a DAY 20 348.0 335.7 355.8 374.4 304.4 DAY 24 380.1 359.4 379.8 406.2 326.1 SD test day 24 SD test day 24 SD test day 24 SD test day 24 SD test day 24 DuPont-2932 du0 I 1 % (I) a Ratsmot weighed, ----------o2-9.(.o-P-------------- -60- ueduioO > H-24043: Biopersistence Screening 1Q-Dose Oral Gavage Study in Rats_______ ANIMAL NUMBER DAY 1 DAY 2 # H-24020 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP V TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 627757 627760 627765 627772 627781 221.2 226.2 228.3 245.2 219.0 225.4 232.0 235.3 256.4 226.3 236.3 244.4 247.1 266.2 236.5 241.1 251.7 251.6 277.0 242.9 247.9 260.2 256.4 276.9 247.2 252.2 254.5 261.1 285.0 251.6 254.4 258.3 264.7 291.0 256.1 ANIMAL NUMBER DAY 8 DAY 9 TEST DAYS DAY 10 DAY 13 DAY 20 DAY 24 DAY 34 627757 627760 627765 627772 627781 269.1 262.6 271.5 300.9 258.1 276.7 280.3 282.4 307.5 266.8 279.7 287.3 288.1 317.0 271.2 -a -a 324.3 348.6 349.8 375.5 315.1 343.0 379.9 382.7 404.0 338.8 372.3 419.4 400.9 446.9 372.0 ANIMAL NUMBER DAY 41 U3>Noo. 627757 627760 627765 ao9*3aooa3. 627772 627781 (O>pO0> a Rats not weighed. ______________ 402.8 437.7 422.9 478.4 389.9 DAY 47 419.7 448.9 444.8 494.3 408.2 TEST DAYS DAY 52 436.7 456.5 455.6 513.5 421.0 SD test day 52 SD test day 52 SD test day 52 SD test day 52 SD test day 52 -61 - # DuPont-2932 Company Sanitized. Does not contain TSCA CBI 6 H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 % H-24020 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP VI TEST DAYS DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 627762 627769 627775 627778 627783 227.2 231.1 224.7 213.1 216.4 235.0 241.1 235.7 217.4 218.2 248.7 255.9 246.8 221.3 226.6 257.3 264.2 254.7 225.5 232.0 263.0 272.3 265.7 230.1 238.0 275.1 286.3 276.7 236.9 243.9 279.7 289.9 280.2 240.4 247.6 ANIMAL NUMBER DAY 8 DAY 9 TEST DAYS DAY 10 DAY 13 DAY 20 DAY 24 DAY 34 627762 627769 627775 627778 627783 ANIMAL NUMBER 627762 627769 627775 627778 627783 285.9 302. 286.6 244.8 256.6 DAY 41 438.7 479.7 433.2 356.8 409.6 299.1 309.6 296.0 250.8 259.2 DAY 47 439.9 474.6 451.1 373.5 426.9 301.5 312.5 304.5 255.1 264.3 -a -a -a -a TEST DAYS DAY 52 DAY 55 _a __a _a __a _a 453.5 512.2 460.8 386.0 449.0 356.5 386.6 353.3 294.0 311.3 DAY 61 473.0 511.4 477.4 393.3 473.8 381.5 414.4 377.4 320.0 340.9 DAY 68 471.6 531.4 478.6 398.3 474.8 419.6 456.5 413.9 347.1 380.0 a Rats not weighed. -62- # DuPont-2932 H10-2-D40o4se3:OBrailoGpearvsaisgteenScteudSycrieneRniantsg______________ ANIMAL NUMBER DAY 81 DAY 90 H-24020 (POSITIVE CONTROL) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP VI TEST DAYS DAY 94 627762 627769 627775 627778 627783 500.3 566.2 510.4 410.1 508.8 523.3 603.2 537.5 436.5 538.5 528.6 609.6 552.8 445.3 557.2 SD test day 94 SD test day 94 SD test day 94 SD test day 94 SD test day 94 Oe *S< CO S-- 1o 8V3Ooo30)> 3H<O>O/> 09 -63- DuPont-2932 % H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H-24043 (TEST SUBSTANCE) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP I TEST DAYS DAY 3 DAY 4 DAY 5 628254 628266 628267 628270 628279 216.9 219.0 229.4 251.6 221.1 219.1 213.9 230.7 254.8 221.4 227.0 223.0 244.4 264.5 231.1 233.6 233.0 248.8 271.0 238.0 244.7 240.2 260.3 281.0 242.9 SD test day 5 SD test day 5 SD test day 5 SD test day 5 SD test day 5 *03<>o C3D oo(U0) 3oOoan5HC>Oot>o"D. -64- # DuPont-2932 Aiieduiod m H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H-24043 (TEST SUBSTANCE) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP II DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 628253 628256 628258 628276 628278 ANIMAL NUMBER 229.2 219.1 246.0 222.9 256.7 DAY 8 232.9 224.4 251.3 227.0 268.2 241.3 229.4 263.9 239.1 276.8 DAY 9 DAY 10 244.8 236.7 268.2 241.8 285.7 253.2 240.5 275.0 249.7 292.4 255.4 248.6 282.9 255.6 300.8 264.4 252.3 290.5 265.8 307.9 628253 628256 628258 628276 628278 271.8 260.2 299.9 275.7 321.3 284.4 267.7 312.5 286.1 328.2 279.8 274.0 319.9 286.7 329.7 SD test day 10 SD test day 10 SD test day 10 SD test day 10 SD test day 10 & l l \ ta. 3 -t V) O > o s -65- DuPont-2932 li H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 ^ H-24043 (TEST SUBSTANCE) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP III DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 628261 628271 628275 628280 628284 ANIMAL NUMBER 254.4 222.5 241.2 207.2 236.7 DAY 8 264.7 229.3 245.6 206.2 245.1 272.2 238.4 258.7 214.0 251.5 277.7 241.1 266.9 216.3 261.4 DAY 9 DAY 10 DAY 13 288.4 248.0 275.9 223.6 267.7 294.6 259.6 283.4 229.2 278.2 306.1 265.1 285.9 236.3 283.4 628261 628271 628275 628280 628284 309.3 278.4 300.'2 243.5 307.2 326.5 279.2 307.9 244.4 308.5 321.7 290.1 321.9 252.2 324.0 335.5 303.2 345.6 271.4 351.0 SD test day 13 SD test day 13 SD test day 13 SD test day 13 SD test day 13 ^ DuPont-2932 S90Q 'P 3O n o3, 3 -4 UO>o> 00 -66- H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 H-24043 (TEST SUBSTANCE) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP IV DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 628255 628259 628265 628274 628282 ANIMAL NUMBER 628255 628259 628265 628274 628282 231.7 239.7 243.6 212.6 242.7 DAY 8 287.8 289.4 293.8 259.3 277.5 234.5 246.0 251.6 215.3 235.4 244.7 253.2 257.7 228.1 245.1 253.6 260.8 264.1 230.4 248.7 260.3 268.0 273.1 239.7 253.7 268.9 277.1 274.8. 245.6 260.1 274.5 282.0 284.3 249.6 265.2 DAY 9 291.5 295.5 302.1 263.9 285.3 DAY 10 301.0 304.5 312.1 267.7 284.1 DAY 13 _a _a __a __a _a DAY 20 DAY 24 360.4 361.2 383.3 315.3 337.4 391.8 387.1 414.4 342.3 359.8 SD test day 24 SD test day 24 SD test day 24 SD test day 24 SD test day 24 DuPont-2932 .uieyjooyu t-^4Rats not weighed. H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 % H-24043 (TEST SUBSTANCE) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP V DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 628260 628262 628263 628272 628281 ANIMAL NUMBER 628260 628262 628263 628272 628281 O ANIMAL NUMBER o3> 628260 628262 628263 628272 628281 243.1 222.9 249.1 230.2 229.5 246.6 222.1 253.2 236.9 238.7 256.4 233.5 265.6 243.4 240.2 265.4 238.9 268.3 249.1 250.9 268.6 248.2 275.8 253.6 254.4 266.3 255.8 284.1 264.2 267.0 287.7 264.6 289.8 272.5 270.6 DAY 8 290.9 266.7 294.0 279.9 282.5 DAY 9 306.1 279.0 303.3 281.7 293.2 DAY 10 311.6 283.3 307.3 293.4 296.5 DAY 13 a _a _a _a DAY 20 372.2 346.3 355.5 350.6 348.4 DAY 24 _a --a _a _a _a DAY 27 405.3 383.4 383.9 387.3 387.9 DAY 33 DAY 41 DAY 47 DAY 51 429.3 409.5 405.2 413.4 414.4 456.5 449.4 432.6 449.8 447.1 474.7 468.9 457.5 481.8 467.4 490.9 487.6 469.9 505.9 478.4 SD test day 51 SD test day 51 SD test day 51 SD test day 51 SD test day 51 S a n itiz e d . Does not contain tn a Rats not weighed. > O 09 ------------------------------------ -68. 0 DuPont-2932 H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 1 DAY 2 # ______________________________________________________________ DuPont-2932 H-24043 (TEST SUBSTANCE) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP VI DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 628257 628264 628268 628269 628285 ANIMAL NUMBER 628257 628264 628268 628269 628285 ANIMAL NUMBER 628257 628264 628268 628269 628285 230.9 247.4 220.0 214.8 235.5 240.5 255.9 225.2 215.8 236.2 249.5 259.0 233.4 222.9 242.3 259.2 267.5 241.0 230.4 245.0 265.1 278.5 249.9 237.4 256.6 278.5 286.6 260.2 243.7 264.6 281.6 290.4 263.7 245.8 267.1 DAY 8 297.5 306.0 273.0 254.0 280.8 DAY 9 306.7 315.6 282.9 263.7 284.7 DAY 10 310.2 324.8 285.5 267.7 293.8 DAY 13 _a __a _a _a _a DAY 20 385.7 398.4 343.0 312.6 358.4 DAY 24 _a _a _a _a _a DAY 27 426_ .a 3 380.1 345.9 397.0 DAY 33 459.9 488.1 412.5 362.8 436.4 DAY 41 491.9 514.7 443.6 386.7 485.4 DAY 47 516.8 548.3 459.8 401.0 520.8 DAY 51 _a _a _a _a _a DAY 54 540.0 575.6 483.1 422.0 555.5 DAY 60 563.9 595.0 504.3 431.7 588.4 Company Sanitized. Does not contain TSCA CBI a Rats not weighed. -69- H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats ANIMAL NUMBER DAY 76 DAY 82 % H-24043 (TEST SUBSTANCE) INDIVIDUAL BODY WEIGHTS (g) OF MALE RATS GROUP VI DAY 88 DAY 94 628257 628264 628268 628269 628285 604.3 638.7 544.6 463.5 627.7 620.8 655.5 545.4 471.2 647.1 634.2 670.5 558.5 476.0 661.9 647.6 678.2 560.3 478.1 669.2 SD test day 94 SD test day 94 SD test day 94 SD test day 94 SD test day 94 DuPont-2932 sw3tnnU'a TSCACBI -70- H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2932 APPENDIX B Individual Clinical Observations -71 - Conpany Sanitized. Does "contain TSCACBf H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2932 DEIONIZED WATER (NEGATIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS GROUP I Animal Number____________________ Observation________________________Test Day 632649 632650 632651 632652 632653 No abnormalities detected No abnormalities detected No abnormalities detected NO abnormalities detected No abnormalities detected 1-5 1-5 1-5 1-5 1-5 Animal Number 632654 632655 632656 632657 632658 GROUP II Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected NO abnormalities detected Test Day 1-10 1-10 1-10 1-10 1-10 Animal Number 632659 632660 632661 632662 632663 GROUP III Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Test Day 1-13 1-13 1-13 1-13 1-13 Company Sanitized. Does not contain TSCA CBI -72- H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2932 DEIONIZED WATER (NEGATIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS Animal Number 632664 632665 632666 632667 632668 GROUP IV Observation No abnormalities detected No abnormalities detected No abnormalities detected NO abnormalities detected No abnormalities detected Test Day 1-24 1-24 1-24 1-24 1-24 Animal Number 632669 632670 632671 632672 632673 GROUP V Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Test Day 1-52 1-52 1-52 1-52 1-52 Animal Number 632674 632675 632676 632677 632678 GROUP VI Observation No abnormalities detected Hair Loss, Forelimb, Bilateral No abnormalities detected Hair Loss, Forepaw, Bilateral No abnormalities detected No abnormalities detected Hair Loss, Forepaw, Bilateral No abnormalities detected Test Day 1-88 94 1-81 88-94 1-94 1-53 60-94 1-94 Sani,fretf. Dees nof contain TSCACBf -73 - H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2932 CORN OIL (NEGATIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS Animal Number GROUP I Observation Test Day 627789 627801 627805 627810 627818 No abnormalities detected No abnormalities detected No abnormalities detected NO abnormalities detected No abnormalities detected 1-5 1-5 1-5 1-5 1-5 Animal Number 627793 627797 627799 627800 627808 GROUP II Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Test Day 1-10 1-10 1-10 1-10 1-10 Animal Number 627796 627806 627807 627809 627816 GROUP III Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Test Day 1-13 1-13 1-13 1-13 1-13 Con*Pany Sanitized. O* not contain T SC A C B/ -74- H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2932 CORN OIL (NEGATIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS GROUP IV Animal Number____________________ Observation________________________Test Day 627791 627794 627804 627812 627817 No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected 1-24 1-24 1-24 1-24 1-24 Animal Number 627792 627798 627813 627814 627815 GROUP V Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Test Day 1-52 1-52 1-52 1-52 1-52 Animal Number 627795 627811 627819 627820 627821 GROUP VI Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Test Day 1-94 1-94 1-94 1-94 1-94 S m fS n A Offas n o i contain TSCA CBI -75 - H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2932 CORN OIL:ACETONE (NEGATIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS Animal Number GROUP I Observation Test Day 625361 625363 625364 625380 625383 No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected 1-5 1-5 1-5 1-5 1-5 Animal Number 625355 625362 625367 625368 625378 GROUP II Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Test Day 1-10 1-10 1-10 1-10 1-10 Animal Number 625357 625358 625370 625384 625385 GROUP III Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Test Day 1-13 1-13 1-13 1-13 1-13 Qes not contain TSCA C B l -76- H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2932 CORN OIL:ACETONE (NEGATIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS GROUP IV Animal Number____________________ Observation_______________________ Test Day 625354 625365 625371 625376 625381 No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected 1-24 1-24 1-24 1-24 1-24 Animal Number 625356 625359 625360 625372 625374 GROUP V Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Test Day 1-52 1-52 1-52 1-52 1-52 Animal Number 625353 625369 625373 625375 625377 GROUP VI Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Test Day 1-94 1-94 1-94 1-94 1-94 Con^pjoji Sanitized. Does not contain TSCA CBl -77- H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2932 H-24019 (POSITIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS Animal Number 625322 625323 625336 625343 625349 GROUP I Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Test Day 1-5 1-5 1-5 1-5 1-5 Animal Number 625320 625330 625332 625341 625350 GROUP II Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Diarrhea No abnormalities detected Test Day 1-10 1-10 1-10 1-4, 6-10 5 1-10 Animal Number 625321 625327 625342 625345 625348 GROUP III Observation No abnormalities detected . Diarrhea No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Test Day 1-4, 6-13 5 1-13 1-13 1-13 1-13 Company Sanitized. Does not contain TSCA CBI -78- H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2932 H-24019 (POSITIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS Animal Number GROUP IV Observation Test Day 625325 625328 625338 625340 625352 No abnormalities detected No abnormalities detected No abnormalities detected Salivation No abnormalities detected No abnormalities detected 1-24 1-24 1-6, 8-24 7 1-24 1-24 Animal Number 625324 625329 625333 625334 625344 GROUP V Observation No abnormalities detected No abnormalities detected Salivation No abnormalities detected Salivation No abnormalities detected No abnormalities detected Test Day 1-52 1-6, 8-52 7 1-6, 8-52 7 1-52 1-52 Animal Number 625326 625335 625346 625347 625351 GROUP VI Observation No abnormalities detected Salivation Alopecia both front legs Alopecia abdomen No abnormalities detected Salivation Black ocular discharge Yellow-stained perineum Red-stained chin Brown-stained chin No abnormalities detected No abnormalities detected Salivation Test Day 1-6, 9-76, 77-94 7-8 76 7, 8, 9, 10, 13, 20, 27 1-6, 11-94 7-8 8 8 8 9-10 1-94 1-6, 8-94 7 ComPany Santized. *s not conta in TSCA CBI -79- H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats H-24020 (POSITIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS DuPont-2932 Animal Number 627756 627767 627771 627773 627777 GROUP I Observation______________ ;_________ Test Day No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected 1-5 1-5 1-5 1-5 1-5 Animal Number 627768 627774 627776 627782 627785 GROUP II Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Test Day 1-10 1-10 1-10 1-10 1-10 Animal Number 627758 627763 627764 627787 627788 GROUP III Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Wet perineum No abnormalities detected Diarrhea Test Day 1-13 1-13 1-13 1-5, 7-13 6 1-8, 10-13 9 Company Sanitized. Does not contain TSCA CBI -80- H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats H-24020 (POSITIVE CONTROL) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS DuPont-2932 Animal Number 627759 627761 627770 627779 627786 GROUP IV Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Test Day 1-24 1-24 1-24 1-24 1-24 Animal Number 627757 627760 627765 627772 627781 GROUP V Observation No abnormalities detected No abnormalities detected No abnormalities detected Wet perineum No abnormalities detected Wet perineum No abnormalities detected Test Day 1-52 1-52 1, 3-52 2 1, 3-52 2 1-52 Animal Number 627762 627769 627775 627778 627783 GROUP VI Observation No abnormalities detected Diarrhea No abnormalities detected No abnormalities detected Alopecia perineum No abnormalities detected Alopecia both front paws Alopecia right front leg Test Day 1-8, 10-94 9 1-94 1-94 81, 90, 94 1-23, 94 24, 34, 41, 47, 55, 61, 74, 81, 90 Company Sanitized Does not contain TSCA CBI -81 - H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2932 H-24043 (TEST SUBSTANCE) INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS GROUP I Animal Number____________________ Observation_______________________ Test Day 628254 628266 628267 628270 628279 No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected 1-5 1-5 1-5 1-5 1-5 Animal Number 628253 628256 628258 628276 628278 GROUP II Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Test Day 1-10 1-10 1-10 1-10 1-10 Animal Number 628261 628271 628275 628280 628284 GROUP III Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Test Day 1-13 1-13 1-13 1-13 1-13 n> c V a i,, TSCA CBi -82- H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2932 H-24043 (TEST SUBSTANCE) Animal Number 628255 628259 628265 628274 628282 INDIVIDUAL CLINICAL OBSERVATIONS IN MALE RATS GROUP IV Observation Test Day No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected 1-24 1-24 1-24 1-24 1-24 Animal Number 628260 628262 628263 628272 628281 GROUP V Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Sore on neck or chin Test Day 1-51 1-51 1-51 1-51 1-4,7,27-51 5,6,8,9,10,20 Animal Number 628257 628264 628268 628269 628285 GROUP VI Observation No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected Alopecia paw Test Day 1-94 1-94 1-94 1-94 1-7, 10-60,82,88 8,9,76,94 Does notcwtain TSCACB1 -83- H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2932 APPENDIX C Individual Fluorine Levels Company Sanitized. Does not contain TSCA CBI H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2932 Terms: Active % Active Mol Wt Active Formulation Dose % F in Active Mol Wt F TERMS AND CALCULATIONS Fluorine containing compound Tcohme p%onoefnftosrmulation that is made up of fluorine containing The molecular weight of the fluorine containing components (g/mole) The mg of formulation given per kg of animal body weight Tfohrem%ulaftliuoonri(nweeiinghthtebaflsuiso)rine containing components of the The molecular weight of fluorine g/mol Compound Calculations: Dose Active (mg/kg) The mg of fluorine containing compound administered per kg of anim=a(l%boadcytivwee/i1g0h0t.) x Formulation Dose Dose Active (mmole/kg) Tanhiemmalmbooldeyowf efliugohrtine containing compound administered per kg of = dose [mg/kg] / Mol Wt Active [mg/mmol] Dose F (mg/kg) The mg Fluorine administered per kg of animal body weight = (% F in active/100) x Dose Active [mg/kg] Dose F (mmol/kg) The=mDmoosleeFof[mflug/okrgin]e/ aMdmolinWistteFre[dmpge/mr kmgool]f animal body weight Molar Ratio (Active/F) The =mDoloesseoAf cfltuivoerin[me mcoonlt/akign]in/gDcoosme pFo[umnmd ople/rkgm]ole of fluorine NFoorrmmuallaiztiaotnioDn oFsaector oTfhaectfiovremnueleadtieodntdooascehtiheavtewthoeulndobrme areliqzueidreddotsoe administer the amount = (Normalized dose of Active [mmol/kg] / Dose Active [mmol/kg]) x Formulation Dose Company Sanitized. Does not contain TSCA CBI -85 - H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2932 TERMS AND CALCULATIONS Individual Animal Measurement: ppm F in blood The ppm fluoride measured in blood Individual Animal Calculations: pBpkmg 0F.2inpBpmlood minus Tmheeaspuprmedfilnuocroindetromleaansiumreadl binlopolda.smInatmhiisncuasstehethbeavcaklgureowunads fluoride established at 0.2 ppm. ppm F in Blood n0.o1rmmamliozle/dkgtoDose The ppm fluoride minus background that would be expected if the aalsetscuvstdiuev=ylmse.,(med0bsoiu.n1lstiuenis[sewmbanaramesicteoyk0dl.gb/e1krdeogmtuwb]nme/edceAoa)nluc/ksatiegdvmdeiniidfsnfoteiessraeteednr[temoddfmotdhsooeels/sekaocgatf]nu)adaxclbtia(lvpcoeptoimvwdeefFdrlueoionsuresib.neleodToihdnisthe imolar equivalents of active in blood Ti0dn.eh1rpeimlv/aesmdmmoofalrl/oabkrmag[s/aetihcdmetioovflnle/uLtdoh]oreicsnpeoe.pn-mccTeohnnfitltsruaaoiatnrsiioisnnunegmoicnefosfmpltulhpaoasortmninaealenlntcpooilnranmsttmahaielnaiziffnoelgrudmoctrouoilnmaetpioiosnu.nd Note=: ([Nm1pogpr/mmmam-liozl1e]d)mxpgp/mLmol[amr gra/Lti]ofaluctoirvien/eFi[nmbmlooolda/ctMivoel/mWmt oFl F] x 1000 /imol/mmol C mpany S* nHllw t * not contain TSCA CBI -86- H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats DuPont-2932 FACTORS INFLUENCING INTERPRETATION OF KINETIC ANALYSIS Considerations: - cTahuetidoautsalyu.sed for kinetic analysis was from a limited screen and extrapolation should be done -- ASanmalpylteicsailzedaistalouwsed without validation -- TSteeramdiyn-asltaptheansoetmreaaychneodt be reached -- DSoifmfeerecnotmapcotiuvnedasnadrefomrmixutluarteiosnodf oflsueosrwinearteeducseodmpounds --- EDTahifcefhekrcienonemttivpceoshuaincpdlpelmsywaoynerlhyeavutoesepvdleatrsoymddaei,flfinevoreterntfotopsrpmoetuecnliafctiyicoftniossrspureosdourctihnegwtohxoilceitbyody Assumptions: (May or may not bejustified in all cases) -- PAlnaaslmytaicfalulomrientehocdonisceanptprarotiporniastaerfeolrinaellatrywpeitshorfescpoemcpt otounddosse - iEnldimiviindautaiol ncokminpeotincesnctsan be determined based on total fluorine rather than on concentrations of --- M%BaoFclkedgcarutolaaurinswdthepeilga%hsmt FiasluFtholeurionmreionoleefcitsuhle0a.ra2cwptiepvimgeh(tFolufotrhieneacctoivnetacinoimngpocnoemnpt oinnethnet(sf)orimn uthlaetifoonrmulation H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats Data for H- 24019 DuPont-2932 GivMeno:l Wt. Active (g/mole): 497 F%orAmcutilvaetio(Fn CDoonsteai(nmingg/k)gi)n: Formulation: 11000 M%oFl iWn tA. cFti(vge/:mol): 6159 CalcDDuoolssaeeteAAdccVttiivvaeelu((emms:gm/kogle)/:kg): Formulation Dose Normalization Factor: 01.0020 49.7 MDooslearFR(amtimo o(Al/kcgti)v:e/F): 00..035492 Dose F (mg/kg): 6.5 NuRmabt er G62ro5u32p2I 662255332336 662255334439 G66662222ro555533u334223p3326I 625349 Group II 666222555333323200 662255334510 SaTDmeaspytle pBpliomnodF 111 211...630 11 22..69 5555 51.7 733888...570 5 37.1 111000 1100 6615..16 665380...115 Mp0ip.Bn2mulopsoFpBdmikng 01..18 222...474 51.5 733887...358 36.9 65.4 66650207....3999 pNpomrmFailnizBedlotood 0.1 mDmooseles/kg 35..4987 111113...994332 255.96 119817..3857 318893..1359 325.04 233910292...666179 287.76 Eq/umivoallaernts of ABclotiovde in 33116626....39991222 41.54 755998221...335114 1526074.6.692 1903066.9.125 998269770...667997 Company Sanitized. Does not contain TSCA CBi -88- H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats________ Rat Number TDeasyt Sample ppimn F Blood ppBmlooFdin M0i.n2upspBmkg Group III 662255332217 666222555333444852 13 111333 13 6717..52 656472...604 67654167....3840 62.2 G6r2o5u3p25IV 662255333288 662255335420 222444 2244 40.3 4463..32 3491..19 4406..11 443138...790 G66r22o55u33p2294V 666222555333334344 55552222 52 222794...387 2293..18 22227984....1569 23.6 G6r2o5u3p26VI 662255333456 662255335417 999444 9944 12.4 111361...140 11.6 1111110262.....89422 ppm F in Blood N0.1ormmmaloizleesd/ktog Dose 333280240...066796 230892..1330 199.30 221239..7112 210973..2353 114271..1717 111134734...626399 60.63 658430...156118 56.66 DuPont-2932 /molar EofqAuicvtaivleenitns Blood 1991948034..07.6872 985763..9852 616.92 667564091918....25543464 444315476546....93692822 363.08 214897..2639 111679658...134586 Comply S,, ,,, 2(1(( notcontain rscAC| -89- H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats Data for H- 24020 Given: F%MoorAmlcWutilvta.etiAo(FcntiCDvoeons(tega/i(mnmionglg/ek))g:i)n: Formulation: 42206 100 CalcDDuoolssaeeteAAdccVttiivvaeelu((emms:gm/kogle)/:kg): Formulation Dose Normalization Factor: 24002.0.647 DuPont-2932 M%oFl iWn tA. Fcti(vge/m: ol): 6199 DMooslearFR(amtimo o(Al/kcgti)v:e/F): 00..076256 Dose F (mg/kg): 13.8 NuRmabt er G6622ro7777u77p13I 662277776576 627777 G6622ro7777u77p13I 666222777777765776 Group II 666222777777677864 662277778852 SaTDmeaspytle 1 111 1 55 555 111000 1100 pBpliomnodF 183.1.2 111460...157 66876405....8830 71.6 56.3 46555341....1680 ppBmlooFdin M0i.n2upspBmkg 1117633..9..390 10.5 6756..16 677941...846 555640...168 4643..94 pNpomrmFailnizBedlotood 0.1 mDmooseles/kg 2176..6839 223924...637172 111435179...869606 115629..0987 119.49 11910268.4..32400 138.24 pmolar EofqAuBiclvotaiovldeenitns 1951748..22.1502 17060.0.792 458424..6210 456788..1226 517.39 430668..5122 433719054...624599 C mj*any S a n a ta *. Does noi contain TSCA CB| -90- H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats_____________________________________________ -_______________ DuPont-2932 Test ppm F NuRmabt er SaDmapyle Blionod ppBmlooFdin M0i.n2upspBmkg ppm F in Blood N0.1ormmmaloizleesd/ktog Dose Equimvaollaernts of ABclotiovde in Group III 662277775684 662277776837 627788 1133 1133 13 4230..57 3103..82 24.9 4230..35 231403...760 429372...266379 6525..6118 313.77 21924418..2.75054 178.99 G666r222o777u777p577990IV 662277776816 24 2244 2244 11914.2..69 96..97 11941.0..74 96..57 19.17 65.22 2314..3218 2103..6856 147807206...612.51092 G66r22o77u77p8517V 666222777777676520 5522 555222 00..96 001...890 00..74 000...876 01..8459 111...274809 2555....09807700 4.35 G6r2o7u7p78VI 662277778632 662277777659 94 9944 9944 0.3 <00.2.2 <00.2.2 0*.1 0.0 0*.0 0.*21 00..*0000 0.*72 00..0000 * = Below LOD (Level of Detection) -91 - 0'Besrt^cniaio * s c a C B/ H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats Data for H-24043 Given: MFoorml Wulta.tiAocntiDveos(eg/(mmogl/ek)g:): % Active (F Containing) in Formulation: 494 100 25 CalcDuolsaeteAdcVtivaelu(ems:g/kg): FDoorsmeuAlacttiiovneD(mosmeoNleo/krmg)a:lization Factor: 205.051 197.6 DuPont-2932 % F in Active: 60 Mol Wt. F (g/mol): 19 DMooslearFR(amtimo o(Al/kcgti)v:e/F): 00..076894 Dose F (mg/kg): 15 NuRmabt er Test SaDmapyle pBpliomnodF ppBmlooFdin M0i.n2upspBmkg G666222ro88822u2567p460I 662288227697 11 111 4665....9224 6.6 45..70 66..20 6.4 G62ro82u7p0I 628254 666222888222667769 55 555 12.7 ' 1993...691 11.6 192.4.5 11912.7..49 G6r2o8u2p58II 662288227586 662288225736 111000 1100 1165..50 1176..80 11.5 111646...388 1116..36 ' pN0p.1omrmmFmailnoizlBeesdl/oktoogd Dose 99..8289 111212...628556 2148..7507 221259...541397 29.24 3323..2210 2322..3830 /molar EofqAuBiclvotaiovldeenitns 3331..3333 444210...630370 668423...636377 7866..0000 19088.6.677 111102..6070 75.33 oesC o m p ly Sanftixed. not W a in TSCACBI H-24043: Biopersistence Screening 10-Dose Oral Gavage Study in Rats_____________________________________________________________ DuPont-2932 NuRmabt er SaTDmeaspytle ppimn F Blood ppm F in M0i.Bn2ulopsopBdmkg pNpomrmFailnizBedlotood ' 0.1 mDmooseles/kg Hmolar EofquAicvtaivleenitns Blood G6r2o8u2p8I4II 666622228888222267781150 1111133333 5.1 6555....1579 4.9 4655....5397 119921..66..828846 3322..6677 4338..3030 10.47 35.33 G66r22o88u22p5559IV 666222888222687524 2244 222444 43..72 444...590 43..50 443...378 95878.....5295813909 20.00 3310..3030 2258..3637 G66r22o88u22p6722V 662288228610 628263 5522 5522 52 2.1 221...249 2.3 11..97 22..02 2.1 33..7356 1112..3637 43..3955 4.15 111434...360370 G66r22o88u22p6689VI 666222888222856574 9944 999444 00..86 001...189 00..64 000...976 01..7199 111...731889 42644.....6600077000 C-XP" S M U 0MS no( -93 - tsca CB|