Document jyD2kr7YayEze94wvv07J1LVN

ARR26 _ 1492 13 ff: DuPont13309 Perfluorooctanoic Acid: Lactational and Placental Transport Pharmacokinetic Study in Rats `Work Request Number 14787 Service Code 1569 Protocol Haskell Animal Welfare Committee Number: <> g 5L7? 5R on8 Z 33 & a LaPcetrfsiivoornoaolcstaandcPilcaAcceindt:alTransportPharmacokineticStudyinRats DuPont13309 `TABLE OF CONTENTS Page INTRODUCTION. sss:3 OBIECTIVErr mrmmessmmmsmsmsssssmssssmsmm---- `SPONSOR AND TEST FACILITY... 3 REGULATORY COMPLIANCE... Er A. D056 Group Subsets 0d DOSING SCHEAUIES....vrerrerrmreerremrnons B. SelectionOf DOSE LEVIS... C. Gestation Subset Sacrifice ScheduleAnd Sale COSCON ......crrrrrerrns D. Lactation Subset Sample Collection And Sacrifice SCheule.......onrmrrernns MATA.ERTISAELSS UANBDSMEET.cH.OcrDeSsr.m.mr.rmeermrmmmsemmssmssmsnemseeemenresmsmeone& Be VER vncnmigpugipmmpmimimntgimrmmssimsmmsimd) CD. ATesBt SSubstsancre Adiminmistmratmionm, Prmepasratimon,--an--d S--AP--IG--.--.--..--.u--vu--r--rr--en--sT6 F. RADAOMUZBON o.com Ge AQUI FEMALE RAS... SAMPLE ANALYSES ..cccovmsmssssmssssssmmsssssssssmmsmssmmsnsssmnon 1 STATISTICAL ANALYSES corms 11 SAFETY PRECAUTIONS AND DISPOSAL OF WASTE MATERIAL ...ccrcsr 11 RECORDS AND SAMPLE STORAGE... 11 STUDY PERSONNEL css 11 STUDY DATES...convmmenmmmeummmmmmsssmmmssmsmssmesiommsssmmnon 13 2. LaPcetrafliuoonraolosatnadncPilcacAecnitda:l TransportPharmacokinetic StdyinRts DuPont13305 INTRODUCTION T`hmeettaebsotlsiusbmstsatundciee,sPweirtfhluPoFrOooAc,tawnhooileaecbiod,diyselismuirnfaatcitoannotifntihneducsotmripaolupnrodcewsassesf.oIunndratto be much `trmaonrseproarpticdoinncefnetmraalteisoncsoomfptahreedtestto mmaatleersiaflowllhoewninagdmoiranlisdtoesriendg,tohopwreevgenarn,tafvaeimlaalbelse idsaltiamoitnetdhien `smcialpkefarnodmtlachtartiisnnegofeemalxesi.(stdaianongtheconcentraotfitohne testmaterial transpovriattehde OBJECTIVE `pTlhaesomb,jepcltaicveenotfatlh,iesmsbtruydoyniisc,tofeeavla,lauantdentehoenactoanlcetnitsrsauet(iso)nsfoolfloPwFiOngAreipnemaatteedrnoarallmdiolskiangnodfbtlhoeod dam at three concentrations. SPONSOR AND TEST FACILITY C`Tohmispastnuyd,y Wisilcmoin-gstopno,nDesbloaywr3areMe,d. STt.hePasuplo,nsMoirn'nsesaoptpar,ovaanldwEa.sIcdfufePcotinvtedteheNdeamtoeutrhse sapnodnsor aHealuth tandthEhnevwoiororrnkmoenintthalzecSoceniternacdcets.,TEh.1esdtuuPdoynwtildlebNeecmoonudrusctaenddaCtoHmapsaknelyl,LNaebwoarartko,rDyfeloarware. REGULATORY COMPLIANCE "STthainsdsatrudsd,y wwihlilcbheacreoncdouncstisetdeinnt cwiotmhpltihaenOceEwCiDthParlilncaippplleiscoafblGeoGoododLaLbaobroartaotroyryPrParcatcitciec(eas revised in 1997) published in ENV/MC/CHEM(98)a1n7dMAFF JapanGood Laboratory Practice Standards (59 NohSan Number 3850.54 _--m 3 LaPcetrativoonraolocatnadnPcliacAecnitda:l TrasportPharmacokinetic StdyinRats STUDY DESIGN `The study design is as follows: -- Group Dose _(mg/kg/day) Suspension Concentration (mgmL)* Time-Mated Females I 0 in 3 0 06 20 20 m 10 20 v 30 50 20 20 "TF daFiorlmyublyatoiroanlsgoafvategset tuabsdaonicnegivodlluomiezoefdwmatgerw.il os admired aos b Taodascthidevoorthsesaecomnpcaepnrtrlat0ie4o)n.sof activeingrdiet,theformulationswillbo TShiecgon.trol group imalwill ceivevehicledeionizedwateonlyat DuPont13309 A. Dose Group Subsets and Dosing Schedules Female SubsetA Growp Do4s-e1D0a6ys I5 I5 i5 vGee 5 b Posen Female SubsetB Do4s-e1D5a6ys 5 5 5 5 Female SubsetC Do4s-e2D1a6ys 5 5 5 5 Female SubsetD D4ogs-e2iDpapy>s s 5 5 5 t`hTihredfirass5saunbismeatlCs,ianndetachhegrreomuapinwiilnlgb5eadsesSiugbnsaetteDd.as SubsetA,thesecond 5 as SubsetB,the B. Selectionof Dose Levels Dose levels selected for this study were based upon the resultsof a two-generation reproduction s 30 tmgi/unkgad/tdsay.y"foGrraopupprsooxifma3t0emlayl7e0andady3s0bfefeomraelecrohaatbsiwteatrieodno.sDeodsbiynogroafltghaevPaOgefaemta0l,e1s.,3,10, or ecxocnetpitniuoendofthsriogungifhiocuatnmtlaytriendg,ucgeedstkaitidonne,yawnedilgahcttaatinodkn iodr naepypwroexiigmhattetlo yt1er1m2indaalysbotodtyal,weWiightth atnhed 030bmrga/ikngw/ediagyh.t Oraftfisops,rinnogtmeosrttsaluibtsyt,aantcterirbeultaetdedtomaftaeirlunraelttootxhirciivtey,wwaassoobbsseerrvveeddaitndFo,segsenueprattoion weanlings at 30 mg/kg/day. -_-- oea LaPcetrafilounoarlaoaodcPtlaaAnccenitdca:lTransportPharmacokinet StdyinRts C. Gestation Subset Sacrifice Schedule And Sample Collection Dupont13309 Terminal Subset A" Sacrifice 10Gafterdosing Matemal Blood, AmnioticSaFlmupilde,sPCloalcleencttse,dWholeEmbryos B 15Gafter dosing 21G after dosing MMsatteemmaall BBlloooodd,, AAmmnniioottiicc FFlluuiidd,, PPllaacceennttaass,, WWhhoolleeEfmetburseys,osFetal -- 00 BBoloodd 000 + Maternal blood semple volume 0.5mLper animal collected in tubes containing heparin + Amniotic Fluid semple minimum volume approximately 100 uL collected in glass tubes + Fheetpaalribnlood sample minimum volume approximately 100 uL collected in tubes containing + All embryos and fetuses collectedincryotox tubes D. Lactation Subsct Sample Collection And Sacrifice Schedule Subset D Numberof Females/Litters Maternal | Samples NTeruminmaolfbSPaucerpisffircoer Pup Samples DDaayy 73pppaafftteerrddoossiinngg S/goup Slgroup Milk, Blood Milk, Blood Minimum Minimum o1fperlitte? of1 per litter ~~ Blood Blood Day l4ppafterdosing Day21pp-after ~~ Slgroup Sigowp Milk, Blood Milk,Blood MMiniimnumoioff1mI ppeerurlliittmtteerr Blood Blood daosiAnng!thediscretionof thesadydirecor, sample volumes for analysis he amberofpapssacriiced aybe creased enerefi b Matera Terminal Sacrifice + Maternalmilksampleminimumvolumeapproximately 100 uL collectedin glasstubes + Maternal blood sample volume 0.5mLperanimal collected in tubescontainingheparin + Fheetpaalribnloodsampleminimum volume approximately 100 uL collected in tubes containing _-- ---------------------------- osafc LaPcetrafitvornoaolcaianndoPilcaAcceindt:alTransport Pharmacokinetic StudyinRais MATERIALS AND METHODS DuPont13309 A. Test Substance 1 ldentification "LTahbeorteasttosruybNstuamnbceerwiHl-l2b4e92ob1tauipnoendfrrecoemip3t.M,AvSati.lPaabulle,iMnifnonremsaottiao,n aonndtwheaspuraistsyi,gnceodmpHoassikteiloln, cthoentvaemnidnoarntasn,dsdyoncounmyemnst,ehdazianrtdhse, satnuddyharzeacrodrodussanmadtreerpioarlt.classifcation(s) will be provided by 2 Purity `The vendor reported purity was 95.2 %. 3. Test Substance Stability `aTnhaelyssets acobnodiufcltthieedttneesyatrstuhbsetbaengcienonvienrgtahnedcoeunrdosefotfhethsetsutduyd.y willbeconfibrypmureitdy B. Vehicle `The vehicle will be Nano-Pure water. C. Test Substance Administration, Preperation, and Sampling 1. Administration A"nTihemtaelsstassusbisgtnaencdewtoiglelsbteataidomnisnuibssteetrseAdb,yBo,raanldgaCv,waigelobnecdeodasieldyfoar7ad,o1s2e,avnodlu1m8edaoyfs5 mL/kg, 4re7spdeacytsi.velFye.maAlneismianltshaespsriogcneesdsotoftdheelilvaectraytoiornsshuobwsientg(Ds)igwnisllofbdeeldiovseerdywfiorllapnportobxeimdaotseeldy. Dose `volumes will be adjusted daily based on body weights 2. Preperation tSeomlputeiroantsuorfetuhnetilteusstesdu.bsTthaencmeeitnhtohdeovfemhiixclienwgiltlhebetepstrespuabrsetdandcaeilwyiathndthsetovreehdicatlerwoiolml be documented in the study records. 3. Sampling nSeacmepslsaersoy,facddaicthiotneastl ssoalmuptlioens(msapyprboexitmaakteenlayt3thmeLd)iswcirletbioenotafktehne3sttuidmyedsidruercitnogrtohredsetsuidgyn.eeI.f EE 6 ---- ---------------------- LaPcetraftioorooaolcatnadnoPilcacAecnitda:l TraasporPharmacokineticStudy inRats DuPont 13309 sAhnoarltylsyeasftwielplraedpdarreastsiocnontcoetnhteraAtniaolny,tihcoamlogGernoeuiptya,t Haansdkesltalb.ility. Sampleswill be submitted + Aannadlwyislilsoafdtdrheesfsirusntsiafmpolrimnogfiwttihlyelbmiexttaukree,nfcronocmednotrsaetpiroenp,earnatdi5o-nhnoeuarrrtohoembteegmipnenriantguorfestudy stability. v`eThhrieceleinadnedp2ensdaemnptlseasmfplreosm cfarcohmteeascthsutsesptesnosliuotniownilwlilblebaenaclolylzeecdteidm.meOdnieatsealmypalfetoerfthe submission. stability. `Thethird sample will be held or5 hoursat room temperature, then analyzed for + Ftohretshtuedsye,caonnaldyasnids wtihlilrdasdadmrpeslsincgonscteanktreantirono.mdosepreparationnearthemiddleandendof aSnaamlpylzeesdoifmtmheedivaetheicllyefaonldow2isnagmspulbemsifsrsoimoneatochvecriofnyccoenncetnrtraaottfiitoonh.ne solutions will be Icfosnadmucptleeds.caOnnnodtabyesasnaamlpylzeesdaartetthaeksepne,ctihfeiesodltuitmieosn,strheemyewiinlilnbgeafftreorzdeonsuinntgilwainlallbyesesstcoraendbien the Arenfarliygteircaatlorstfourdyadrdeictoirodnsa.l analysis. The analytical method used will be documented in the D. Animals 1. Species (Strain) Crl:CDSD)IGS BR rats 2. Reason for Selection Trheecroamtmewnadsseedlebcytetdhfe oguitdielsisnteus.dyTahsietCirla:pCrDe*f(erSrDe)dIsGpSecBiResfstorrarienpwraosduscetliecvteetdoxbiacsietdytoenstingas Lcoanbsoirsatteonrtyl.y acceptable health status and on extensive experience with this stein at Haskell 3. Description EiJuglhyt1y1n,u2l0l0ip3a(ro2u0sf,etmiamlee-sm)aftreodmfeCmhaalrelse,swRiilvlebreLraebcoeriavtoerdioesn,JIunlcy.8R,a2l0ei0g3h,(6N0ofretmhaClaerso)lainnad, The rlaotcsatfioornthoiftshsetusduypwpleireerr(eciqtuye/ssttaetde)towbiel6b3eddaoycsumoledntaendd bineathe1dstauydyofrgeecsotradstiaonnd(fdienayl0rGe)pourtp.onThe varernivdaolr.; hTohwiesvaegre,ctohrerweesipgonhdtsratongaeniesntoitmaatefadcwteorigfhorttrhaenpgueorpfos2e0s1o-f2t2h5igssrtaumdsyaacncdo,rdtihnegretfoorteh,e deviations outsideofthis range are expected not to have any impact on the study.Bodyweights EE 27. ---- -------------- LaPcetrfalisoonroaolcatnandoPilcaAcceindt:alTransportPhamsacokintcStyinRas DuPont13309 owniltlhebedadyoctuhmeernattseadrienmtahteesdtu,ddyayre0cGo,rwdsilalnbdepsurppoliveidbinyttdhheeefviendanldorerp.oTrtheday0G bodyweights BsEouaptcphhlitrehartepiHrsaiasoskrsetliolgnsaehndiipampuiannlign.quuUmepbneournmarbenecdreaiupnnti,dqieudaeecnvhteianfndiioemrdawalinwtiihmlaalnbneAuaVmsIbseDigrMnwieicdlrlaocHbhaesirkpeeiclmolprladenadinmtoabnlyentauhcmehber. `cuangiequcearAdV. IADmMaisctreorclhiistpoifumnpliaqnutenvuemnbdeorrsnwuimllbebresm,aHianstkaeilnledanwiimtahltnheusmtbuedrysr,eacnorddcso.rresponding E. Animal Husbandry 1. Environmental Conditions A(rnefillaumtoairvelesrchoeunomtmildsiigwthiytol)lfobn3ea0mn-ai7an0ptp%ar(iotnxaeirdmgaeattteeda1tt2oem4hp0oe-ur6ra0tl%ui)rgeh.to/fAdan1ri8km-ca2yl6clreC.oo(mUtnsalrwgeiesltslejdbuteodag2re2tdi-bf2iy4ctiaChl)leyasinltdluudamyinated dirreelcattiovreohrutmihdeitlaybaornadtotreymvpeetreartinuarreiranangtoehsaivnetshieghnoiufiscianngtlryoaofmfsecwtieldltbheerreescuolrtdseodfbtuhtewsitllundottyhb,ee included in the fina report. 2. Housing cAlalgerbaotsarwdilulntbielhsoaucsreidfiioncdreivdiadyua1ll9yG.inFsetamianlleesssssetleeelc,tewdfiroer-tmheeshlaccatgaetiso,nssuusbpseentd(eDd)swihlolvebe housed inpolycarbonatepanscontainingbeddingmaterialonday 20Gthrodauy2g1php. 3. Food ARloldeantts LwaiblDlbieetpro5v0i0d2edatdalpiwbaittuem.randpelletedPMI NutritionIntemational, LLC Certified 4 Water `Water from United Water Delaware wil be available ad libitum, 5. Animal Health Monitoring paArrseogsbpreealcmoi,fwitethdheoifsnoetlthlheoawtDiwunoPguoplnrdotcbHeaedsuekrxeeplselcLatareebdopretaortfioomrrpymaaecndtiptmheaerlisochideeainlcttiahflitalconyidnetenensgvruiirtreyootnhfmaettnhcteoanslttumadomyni:intaonrtilnegvels + aWnadteorthsearmcpolnetsamairneaanntasl.yzed for total bacterial counts, and the presenceofcoliforms, lead, + Feedsamplesareanalyzedfortotal bacterial,sporeandfungalcounts. _-- - -------- KPaecrtflaaioornoosctnandoPicaAccidt: Transpo Pharmacokinetic SeyinRats Dubos 13309 + Sbaymtphleecsafgreowmasfrheesrhsly washedcagesandcageracksareanalyzedtoensureadequatesanitation Csrepereqtcuiiiffriieeemddehannetiasmvaaylnmdefetneaodltist,souaesfxelcadte,oegxduians,rtaacthneltdoermeidanbaxtyietmdhuheymmdarconocunacfreabncottnrusar,teiraotnnodomoferkgeeatynsacppoehncotisafpmihieadntnaeunstt.tsi,t`iiTohnnecalluding `pwroeusledncneootfbteheexspeeccotnetdatmoiniamnptasctbethleowinthteemgaorxfiitmthuyemsctoundcy.entration stated by the manufacturer ilhncealaundibemdaoilannhterihamelaatflihvnaaetltnerdroeeipnnoarvrrtiiraayotnn.tmhDeeandttiaaslcarmreoetnimioantioonfrtitanhigenpsertdousgderypdeairmraietsceatldoymfr.irnoimsstetrueddybreyctohredastatnedndmianygbe 6. Quarantine aRantdstwhielnlrbeeleqausaerdanfotrintehde asctcuodryduipnogntoappprroocveadluroeftshoeutLlaibnoerdaitnorHyasAkneilmlaLlabVoertaetroirnyarSiOanPoLrA2OO3-P, designee. mcRhaaetycskbtehfaoetrmdtpihlceoopyrreeadsreeantsctaehcoreiffddiiicssecedraeistnieo.enxtoDrfetephmeienssddteuunrdtiyndugiprtoehncettoqhrue,asretahnfetinipdnaitenhpgosel,roigfoiudsrttwhiaelsrlsdibigeangenndeocstrtooitpchspeiresodtctueodduyroers the laboratory veterinarian. F. Randomization raaUnnpdkoeneadxrwpreiirtvihamile,nntdthaaelmisrgrrweoisulpplesbctbeiayvsresailngondteodomtnstoahlmeoptblsaiasnicgscoofrfrdodimantgyhtOeoGrtabhnoekiderygdewlseitsita.gthiTothnsdaeandyid.satTsrhisbeiugntn,ieotdnhtesohycowouinlltdlrbroeelsult einxcmeesasinvebowdeyigwhetigohrtaspfpoeraarllillgrproiuoprsttohatthearsetnaototsftdaotissitnicgawlillydlibfeferreenmto(vped>f0r.o05m).theDsatmudsty.hat lose: G. Adult Female Rats 1. In-ife ObservationsofFemales a Body Weight Bodyweightswillberecordedonthedayaferarrivalanddailyuntiltheend ofth study. 2. Clinical Observations Clinical observations will be recorded on the day after aiva and daily until the endofth study. _-- 9. EE ------EH ------------------ LaPcetrfaloonraoolsatnadnPcliacAecnitda:l TransportPharmacokinet StyinRs H. Gestation Procedures Dupont13309 Obny dcaayrb1o0n,d1i5o,xiadnedin2h1aGl,aatinoinm.alFsoarsesaicghnefdetmaoleSuwbistehtAvi,siBb,laenidmpCl,anrtateiosn spitees,cwthiteliibntervaeuuettehrliannyeiz,ed rleoscoartpitoinoonf)ewaiclhl beembrercyoord(eDd.ayA10graonsds e15xaGm)inoartfieotnuso,famnadteimmpallanvtiastcieornatwyiplle b(leivdeoonrecaanrldylesions nsoatmepdlewsilflrboemreeatcahindedamfowriflulrbtheercoelxlaemctiendatfiroonmatthtehveedniasccraevtaioanopfptrohxeimsattuedlyyd2irehcotuorr.s Blood i(m#p3l0anmtiantuitoenss)itpeo,satn-ddoasllepalnadcepnrtoacsesasneddetmobroybotsa/infeptluassemsawislalmpbleesc.ollAecmtneido.tiOcnfdluaiyd2f1rGo,m feeatcuhses swialmlplbeeseuwitlhlabneizteadkewnitfhraonmoavetrdrosaeninsjcevucttiemonar(disep)teooftshoedcairuomtipdeanrttoebrayrb.ital and fetal blood aFenmdaalegrstohssatpdoisetmoorarrteesmacerxiafmiicneadtiinonexpterrefmoirsmeddu.rinLgestihoegnesswtialtliboenorretpaeirnieoddawtitlhlebdeisncercertoiposnioefd the csatrucdaysdsiersecwtiolrl,btehedipsactahrodleodg.ist assigned to the study, or the laboratory veterinarian. Dam I Lactation Procedures (`Tdhaeysda0y,3w,h7e,n14d,elainvder2y1ispocsotmppalrettuem)i,s dofefssipgrniantgedwidlalybe0 pinodsitvpiadrutaulml.y hAatndelaecdhaenxdameixnaamtiinonedpefroirod `aanbdndoermaadlpbuephsaivnieoracahndliatpeprewairlalnbcee;coaunnytdeedabdy, smiesxsiens gs,ooornaabsnpoorsmsailblpeuapfsewridlellbieverreyciosrdceodm.plLeitveed and litter weights will be recorded. Dead pups will be discarded. Oinnhdalaaytison3.,7D,aurnidng14adPmPi,nainsitmraaltisaonsosfiagnneesdttheosiSsu,bsmeitlDk,awnidllbbleooadnessatmhpelteisze(dobrbyiItaslofsilnoursa)nweill be Dcoallmesctewdi.ll bBeloroedmosavmepdlefsrowmiltlhebier clotltlresctaepdparpopxriomxaitmealtye1l-y22hhoouurrssb(e+fo3r0e mthienumtielsk)ipnogsptr-odcoseed.ure cibrecgiunlsa.tinDgaho3ytwlaittteerrspwaidll,hbeeakteepdtgwealrpmacdkusr,ionrghtehaetablasmepn.ceDoafmtshwedialmbbeyrtehe tseuotoftrheeiintrhleei&trtders after recovery from anesthesia. Raanndovoemrldoysseeliencjetcetdipounp(sipf)roofmstohdeisuemdapemnstowbialrblibteale.utPhuapnibzleodoodnstahmepslaesmewpilolsbtepatratkuemndfaryosmw&ith trMaantsevrenraslecanudtpmuapdebtloootdhseacamrpolteisdawirltlebreypornodcaeysss3aetndodob7otarifnrpolmatshmaevseanmpalceasvaanodnpduapys w1i4lPlPb.e discarded. Oannesdtaheysi2a1,PPm,ilaknismaamlpslewsilwlibllebaenecsotlhleetctiezde.d bAyftIesromfillorkanceolilnehcatlaitoinobnu.tDbuerfiornegraedcmoivneirsyt,radtaimonsowfill b2heoeuurtsha(n=iz3e0dmbiynuetxessa)ngpuoisnta-tdioosne.anBdltohode sdaammpwliesl wbielldibsecatradkeend.fRraonmdtohreavleynsaelceacvtaeadpppurposxfirmaotme.ly these dams will be euthanized with an overdose injection (ip)ofsodium pentobarbital. Pup. -_-- "e0e ---------------------------------- LPacetcttounoalraonodtPalAancceoindit:al Traaspor PharmacokineticStdy iRats Dupont13309 bprloocoedsssaemdptloeosbwtialilnbpeltaaskmeansfarmoplmetshaenvedndaacmasvaa.ndMpautpesmwaillalnbdepdiuspcbalrodeodd.sampleswillbe SAMPLE ANALYSES SSaammpplleess nwoiltlrbeequainrailngyzperdocfeosrstiensgt mwaitlelrbiealstcoornecdenattraaptpironoxbiymattheelHya-sk1e5llCTaosxiscooolnoagsypgorsosuipb.le after pcorlolceecstsiionngaanndduanntaillyasniasl.ysHisP,LoCth-eMrwSisoer,ansoatmhpelressuiwtilalblbeeasntaolryetdicuanldmeertthhoedsawimlel cboenudsiteidofnos aunataillyze samples. The method used will be documented in the study records, STATISTICAL ANALYSES e`vGarlouuaptmioenasnmsaayndbecopnecrefnotrramteidiofnndeacteaswsilalbreyr.epresented as Mean + SD. Other statistical SAFETY PRECAUTIONS AND DISPOSAL OF WASTE MATERIAL `cGoonotdamhionuasteikoenoepfidnogspironcgesdoulruetisowniplrlebpeaprrataicotnicfeadctiloitaevso.idTpootaevnotiidalshkienalctonhhtaaczta,rgdlsoavensdwill be `wiwlolrnbewhheanndhlaenddilninagecihtehmeirctahlehoteosdt.suDbosstianncgeosorlduotisoinnsgwislollubteiopnrse.paIrneadddiinptiroonp,ertlhey tveesnttsiulbastteadnce. areas. Animalcarcasses,foces,andunuseddosingsolutionsanddietwillbeincinerated. RECORDS AND SAMPLE STORAGE NSepweacrikm,enDse(liafwaaprpel,icoarblaet),IrroanwModautnst,aainndRtehceofridnsaMraenpaorgtewmielnltb,eWrieltmaiinnegdtaotn,HaDseklealwlaLraeb.oratory, STUDY PERSONNELpaewi) Study Director: SD SDTitler Analytical Evaluation: < @p -_-- uuee E-- S ---------------------------------- LaPcetraftiioornoaolcatnadnoPilcacAecnidt:al TransportPharmacokineticSudyinRats @PTitlen Dupont13305 STUDY DATES InitiationofTest Substance Administration July 11,2003 In-Life Completion Date: August 22, 2003 (Approximate) REFERENCES 1. `VTainssdueenDiHseturviebult,i1on,,MeKutsalbiokliiss,mB,.La,ndVaElniRmainfaetligohneomf,PeM.rJf.luaonrdoPoecttearnsooinc,ARcei.dEi.n(M1a99l1e).and Female Rats. J. Biochem. Toxicol, 6920, 83-92. 2. DUnupPuobnltisHahsekderlelpoLratb,oDruaPtoonrty-(72407033).. Perfluorooctanoic Acid: Toxicokinetics in the Rat. 3. EPA/FIFRA GoodLaboratoryPractice Standards (40 CFR 160). (1989). 4. OECD PrinciplesofGood ENVMC/CHEM@8)17). Laboratory Practice(asrevised in 1997, Published in 5. MAFF Japan Good Laboratory Practice Standards (59 NohSan Number 3850). 6. ArerpgruosduLcatbioornatsotruideyso(f2a0m02m)o.nOirualm(pgearvfaigueo)ro2o-cgteanneoriacti(oAnP(F0On) ien rwas.-pUelnrpguiebnletirsahetieodrnr)eport. -_-- coeu. --------A ------------------------------------------------ Pectoroosianoi Acid: LaPctsthonaa l sndrPlacm entalaTuc moroldocti_o_SudyinDuRpomae13s30p SIGNATURES Approveaty [a `EveMylchreest Date Te StudyDivcor Te -- ce: <<PQ..&AS..CoConnttaacctt>s> DK..MM.elHlohabtatnon <5P.rCi.mCarrayvTeenchnician> JW. Green -_-- one. A --------------------------------------------------