Document kD5yepknGyK34yJVYKwy3ZnX0

: ARa22.6-1896 : RoiIES IPCNORFNOOFTRIEMDCAETTNIITOOINNAULSNUBDBUEJSREICNTTEHSTESO `RTEODAXAINCCDTSOEUTDBHSFETRRAONLMCAETWSHSICSHODANOSTCRBUOEMLEENANCTT Toxicokinetic Screenof FC Title: Methyl Carboxamide (T-7483) In Rats. "Final Report Date: January 15, 2004 3M Medical Department Study Number: T-7483,1 3M Strategic Toxicology Lab Study Number: ST-45 Author: AndrewM. Seacat Ph.D. ! (3CeMntMeerd2i2c0a-l2ED-e0p2a.rtSmaeinntt,PaCuolrpMorNa.te5T5o1x3i3cology, Strategic Toxicology Laboratory. 3M Study Toxicologist: DeannJa. Luebker, M.S, Study Director: AndrewM Seacat Ph.D, DABT . . Toa sts TONIICPCNROSFONUOTFBREIMSCDATTETAININTOOCINNEASUSLNUDCBBEURJoSEICTnNTEhtS1S)cr Introduction ARENDDAOCTTHEEDRFLRAOWMSTRHAISS PBAEGSE boPeemrptlohuueornrodhasyldeurysoleldayrzabesodpxaaanpmdei/rdoeprrsmotehetacavtboerosbl.iezeTehdfetoosutntrdhuecyat.suroewoflgevcelcraersbiodxuaalmsidinesflsuuogrgoecshtetmhiactatlhey could (CuFd1ysCOObjNe(ctHi)vMe:eT[his study is designed to detercmomiensiphonediFnCg cmaertbhoyxlylcaatrebmooxiaemtiyd,e PLeFmOaAleirnattsheanudrinbee. metabolized to perfluoroIsTc7t4a8g3e.n1s)(PcaFnOAbe)aabcisdo,rbaesdmoeraaslulryepdybmyeesxcarentdion of PMEeMntaahttoe0dasungdM4EFPemFaOleA,AHaTrhleanavSeprraaggeude-reDsaiwdluaelyPrats, 150.250 8 each, received a single oral dose. peFrenomtbalile:ems(HIwanirdteuhvnitSahpetricoaongmurpeoouDmnidtw)h,eyprortaosc,ol,15n0o.2a5n0imaFlasOoeAw,e1rmeaepoorpecss ians3tirnuaggvleePnoFourOasllAyd/dorsuateeotfot2shMoealulvbeeihlaiintcydle2. cSoaatcmhmlpodlopesmeCeonalntldeaccntodiontnoo:lvUegrrriifonyueptwhaonsabdcsaleylnsecc1et.eo2fd3p.b4raeca-kndgoreoundppreov.idSe myatrwiaxsfobreecxotlrlaeccttieodn mfreotmhoaldl rats in SsapmhpyleiaAnoanlyasnids:nUcrroipnseicsdamopnledsaywe7rpeosetx-tdrose,d?Lipvoesst ssegecr wreartsewbeerceolcluetchtaendizferdobmyeCacOh,rat, CMS inthe 3M Environmental Laboratory a(cFteAdCaTn1d Zpaaliy5z8e)d. for the quaniityofPFOA by odRsemesu.eltssTahse ohfitghheestanpaelrycseenstasgheoowfeddotsheatexMcerePtFedOaAA is metalized 10 PFOA following an oral Sanabcdecto2hunrmetaselpdeecftaoinrvd2el5my)a%,loTefhterhaectu,MmwueilPtahtFifOvoeAsAatmdoeournssteoxfeiPxnRegOrhiOgfheePrxFcpOreerAtceebdnytwadigtaehsi7ynthtpahonestfmiadrlostesse24((FFhiiogguuurrrsees {asnaedppEdennvidinirmxoanl1m)ee.nrAtaatssluFLmiamgbaurrseys4oh)f,otwThneherinerseAuslpitpdsuearnldoPmFtOhAenAiennomsnaaersmagsreportcfo(onrFtrA7iCb%uoTtfeTtOtohXePFM1Oe58AP)FifnOroAurmAitnhee material shoving alow background ofAPFiOxi2s.sThhoewnconign pAuprp?eoafrsAnalysisofthe starting MCoEnPclFuOsiAoAn:can be metabolized to PFOA ollowing an ora dos in both male and female rats, : . 2 -- ---- rouss : Signature: AndrCehw oM_Sseacaet, PhD.TDhARTLocal StudyDirector sled Date : ------------r---- ETaiss Figure 1 i cflseiCinaUnreovsrFaro iaseety a, on ~ E Ee ae sa 3PA Bel | BEwE ee lei {OEi | roa 5 w|i EEE Ee ovr reer oer cul pee |S orTele r| ew Te rCeEeLE eerd Ee | EH Time ony | ------ Tfesrs Figure2 1 nNoimcee a. Bi ea a as =] 3N , RCL a = RN - See 5. pi a pits aa 2 fi i larrem [orrsm % Blom) | 18 i I [| Eee | 5 fa FER EnI ew TeT3 eTrTw] fre os Te eos Toi] brew as TsTerrwao amas] . 5 -------- oTaas) Figures On Cu a Ar C Fese y re. gre EE uw SEE et flea EE Sm nN jieRE RR 5 0 REE Fo Hl Li al ji i CHEE Spmi CN =| 0 B[SeEaT || Ea a Caa is Day? . ` EE B fe -- NPont Ac Senoa EesSso uoey s Pyony 7 rt = a Pt e e SSS erRRe I shpep A5E Cs aI 2es Oa. | 5 [eee YE 5$10 i ESEE ore os rb | I o [ERE i Nw fe ee jE ee 2 aR e ET nE a ea on ore , --_-- TStaas : Appendix 1 Individual Results nase((PFFOOAD)oisineh|theiBuronidnyeofr Sex| Group | weight MeetvhyVeloclruamrebaymo[irDdiyeluStdioonos|edsPTOaatAsA]| Gone- TIT --T1---- RE Urino | [SE Factor| Reported |in Urpae Dosoeolrn I] e 2e = [1] "on EEE [7 See a s Cee See Cee Re ee a ee see Cre a | a Cee Eee e a e eee e peepee pee eee eee Tr e w ee o a r eee ee ea Efe e e e ae e Ln ee B pee n t e oe or eee LE meee ee 1.172 CHa La eee on Eee oi eeeee ee oe p hese e ae r e eere e E peee ee l e Taeee s e ony C Ce R r e e e ne e e e eEe Tr meres Te as fe eTe eee Cee ee e afe en Te Sree a eT eae . ------ TStaEs Eee a af H ew Ln i Ht Taare 1 fee ew 1 nt aio 1 e st Te arr --m et le l--y sdso-- = varrer apres Lrr| L nL I [er A REL ET EE L771 LI ti Te RL et CL 0 nL nL rm Ee ef pet r e femr tel ma ws ooa s y rogrs am area owe L ete ods 8L www rIrA | om| el[r oo| n] ne gL nT 11 a er i femstol mow Lr |epei O00{aa [ins aLT 771 Eo 1 [F7oe1[rr7785semmgae ]ste ereo|e| ("o=(sTamei) mikg)EW (G1Ka/i0a05)(1000 Ging) TT 7T----71Tte SLtudy TSotxiucdoyloDgiirsetc:torD:eannaAJ. LnuedbkMerrS,eeMa.cSwa,t Ph.D. . 1 @ HAZLETON weonsrones auenon ne Append SHAVERResitsSesftnry IPABRON. WISST07 + 008)2014a7y + TUX703056HAZRALMOSUD Study: MSaai mbe(Tet 7 scB TloexlissesstaPrsR@OrTiOcoCgOyL|ggrRasbbiTt7s483,STs InAMsetstrlhumosedlnRtevESiqosuiitopnameenVterSyssion:ENMT[Ss239608E 58730C5a06t03t94e0 lJ l A Seat SFiRiepnSeqaanre:d Va: : SSeeeeaAlnaiocshtso3tethinernighgt SeeAtscinens DaDDfactreuoo--ofApenalrsigaomab:er SeeAtachmens go a27u00g8 The 3 coa pa Reduction Amie 000 EEmeso RNAonT-QUAR'IdNESamdpayle1D.a7ta DGorsoew [Sampled Fiemme| FReOpRorTted Nebod| RURIB OBT prt * St=Dv. Bi MBiika G oo17 m tog FSYhsE0 j0a 3270-1 OBe.H8oedeyDipvoeirgiieno,n|do, 100 RTU03270 B53 RIVa5270814 |A0a3r2o80dp} R0228 032000| SFeRo eanngcuespms <t00 Bou l--evasa3 5307 <LoQ M0U03273208301k |[A0c3s2z2Ea8yn0o0n0|| <ctooqg <q OiR soppisr |Re"o55sgn] TT oq vs <0 OsRToIpLrMaS. | [Ataasoo| 136% MORURRTTOILTNL:SS1:15oSop0pa3p1925032T8+09|9 e11h0,o, tori+es Amerside,d 1m 1d9% ois DoT |OOERRMTUIOT2MMTec0o.momMnerrDoTaloy5De. | S00 pSored 00 o Chemical & BioMedical Sciences Division i Epi sSeomeen FSomealA SLE Sea r SeaE 2 SaS Sumseeine r mre " E Smeael Fier . STTasm OOORRRTTEE/SFSAimSEem/kg/gsk/Dmgma/akmyyaDPBaB/DDDy||| 00.225096 0.251 weprellisetedWoneOrtRhecTEshSu/amFnm/asgmregy/drkespdo/urTtrD.ianyprPeDp |TH0v.a3l6o4r Top LiofQmuantiitattion (L0Q):0.0075 g/mi DEaneteedBy: Date Verified! 44/1101/0000 mun 4711/00 MEE, 411/00 kh By: 02i9nt2erchanged fom0h01o32w295they 2 Essss : Appendix3; CarboxamideAnalysis CertificateOfAnalysis - [He March 14,2000 SGos Thissamplewas ang using GC, Lovs, Rib, Pye SMS "H-NMR, FT-IR,an --ee om ---- d. S is te ues. TThhee of ----m---- ----rdcon J ZAOINGHCE ---- io -- i -- e ----r e Unkoown Ms f rr---- eo ont Additionally,the i distributionof tiheesaanglewasdetermined using "F-NMR ml a te rr CFy(CF),- (0)- Rts uesand foun to dtocontain SChPeACF1e:1m)1.ss CimFyFo,a n(aCFa rCy(0)- (pbFsour CFw(eCFr,)v.igC(o0)r- eT cerawir ko mil, ay CFy{CF,),- (CF):(CF,),- Co). Ta (CF;),C(CF),.. C(0)- i