Document Z8yZ3NjDn68evqXg9ajJkNZ1O

$f rIGINAL marsorr | JRAE-0993 Sty Tie Toxicokinetic Study ofPerfluorooctane Sulfonamide (PFOSA; T-7132. 2) in Rats Authors AnTdoxriecwolMo.gySeSapceactiaPlhis.tD. 3M Medical Department, Corporate Toxicology Deanna J. Luebker M.S. `Advanced Texicologist 3M Medical Department, Corporate Toxicology Date: August 11, 2000 StepTsestTingaFactilitysrs 3M Center 270-38-05 Saint Paul, MN 55144 5 on So 73M13S2m2ePgFOTSoxAicPoKlosguydSyTi3n9racs Summary: ePluirmpionsaet:ion kineTthiecsopufrpPoesrefloufortohiosctsatnuedySuwlafsontoamaisdsees(sPtFheOSreAl)atiivnetahbesroartpftioolnl,owmientgabaosliinsgml,e aornadl dose. M80e,thasodtshe: vehicTlewcoongtroolu,psorofS fmigft/ekeng mPaFlOeSaAtsseuascphenrdeecdeiivned22%sTinwgelee ndo8s0eobfyeoirtahlegrav2a%ge.Tween Pwearsflfuoournodocttoabneoa9t6e %(PpOuArAe)Fwiaves rfaotusnfdroatmaealecvheldoosfe g2.r5 onugp/mwlerien tshaecrdiofsiciendgosnoldutaiyosn.1,T4h,eaPndOS29A. pproesstsduorsee.liLqiuivdercharnodmasetroagrwaeprheyaenlaelcytzreosspfroaryPtFaOnSduAmamnadsistssppreecdtircotmeedtmreyt(abHoPlLitCe/sEuSsMiSngMSh)ig,h- Rpeesruflltuso:rooctaneTshuelfvoenhaitcele(PcFonOtSr)olingrliovuepr hoardsenrao. dTehteectPaFblOeSlAevedlosseofgProFuOpShAadordecreasing levels sotfudPyF.OLSiAv,erwciotnhceevrirdaetnicoenosfofcoPnFveOrSsAioanvoefraPgFeOdS7A.0tpopPmF,O3.7Spipn mli,veranadnd0.s1erpaptmhroonugdhaoyust1,th4e, anc. c2o6ncpeosntt-rdaotsieo,nsroefspePcFtiOvSelAy,awvietrhagaenda0p.p3arpepnmt lainvder0.h1elpf.pimfeoonfedlaiymsin|a2tinodn4opfos5t.2dodsayes.resSpeercutmi.vely, easntdimwaetreed utondbeetelcetssabtlhearby4ddaayys.29Lipvosetr-PcoFsOe,Swciotnhceanntraaptpiaornesntwesreeru2m8.h2alpfp-lmi,fe3o7f.4elpipmimnaatnidon23.8 prepsmpe,ctrievperleys.enSteirnagP2F2.O0S%,av3e2r.a3g%e,da8n.d2 2pp5m.,2%8.o6ftphpem,PFanOdS4A.6dopspemd,oonnddaayyss1,1,44 aannddd2a9yp2o9stp-odsotse dose liver rweesrpeec3i5v.2e,ly4.1.1T,heanadve2r3a.g9eptpotmalocnondcaeynstr1a,t4i.onasndof2P9 FpOosSteedqousiev.alreesnptesct(iPveOlyS. PFOSA) in The average pcopnmceontnedataiyo4nspoofstPdFoOsSe aenqudidveaclernetasseidn 1t0he4.s6erpapi:ncorneadsaedy 2fr9opmos8t.5dopspe.mTohnedlaiyve|s ptoossterdaosPeFtO0S8.7 c2onndc2e9nupaotsitodnosraet,ioreisnpcercetaivseeldy.thTrootuaglhoPuFtOtSheesctuuldvaylweintths ivnaltureesloivfer a4.2.nd4.8s.eraandpe5a.k4eodr.odnadyasy1, 4, ppopsmt dPoOseAaAt 3w5a.s4f%ouanndd i6.n0 %theosfetrahoenPdFaOyS| eaqnudivdaalyen4tspodsotseddo.ser,esapnedctievqeulayl.edAn31a.v2e%raagnedo2f40..11%of the POA residual present in the dose, respectively Cliovnecrlaunsdiosnesra: fPoelrlfolwuionrgooacnroarnaelsuelxpfoosnuarmei,dePwFaOsSrAeawdialsyparbosgorrebsesdivferlyommetthaebgoultizaendd tfooPunFdOSin,the `liwvheirc,hraecpcreusmeunltaitnegd22in.t0h%e 3l2iv.e3r%asaenvdi2d5e.nc2e%dobfytthehePhFiOghScAondcoesnetdr,atoinondoafysP1F.4OSarddet2e9ctpeodstindotshee rceasypse.ctTihveelyP.OTAhAe parpepsaernetntinhtahlelisevreaoofnedlaiymsina1 tainodn 4ofpPosFtO-dSoAseincotuhledlibveeracwcaosunatpepdrfoorxibymathtee5.l2y. residual POAA in POAA was found the cosing solution, in this study: therefore. no direct evidence for metabolismof PFOSA to 5 Page20f18 737M1S3a2t2egPiFcOTSoxAicPoKlosgtyudSyTi3n9ras Introduction `cTlheearoabnjceec,tiavnedobfiotlhoisgisctauldpyewrsaisstteonacseosefssPetrhfelpuootreonoticatlanfeosruolrfalonaabmsiodrept(iPonF,OuSrAi)nairny maanldefSecparlague Dmeatwalboelyitreatss oafftPerFaOsSiAngwleasorpalerdfooser.meAdnablyysLiCsMoSf.theUrsienreumanadndfelcievserwefroce PalFsOo ScAollaencdtepdotaenndtimalay bPereavniaoluyszsetdudbiyesLoCnMNS-eatnhdylppeerrhfalpusorootchtearnmeseutlhfoodnsamaisddee(e1)m,etdheneNc-ecstsahryy].derivative ofPFOSA, c`mhirsotmaaketnolgyrcaopnhcylaundaeldyttihceatl PteFcOhnSiAquweausstehdeinultthiomsaetesmtuedtiaebsolwiatse uinnarbaltes (t1o,2d)e;tehcotwePvFeOrS,. thDeiegtaasry administrationof N-ethylperfluoroctanesulfonamidoethanol (N-EXFOSE) inrats, and in-vitro mPeFtOaSboAli(s3,m4b,yanhedpa5)t.ocFyutretsherersmuolrtes,prPiFmaOrSilAy hinsthbeeefnorimdaetnitoifnioedfaPsFapOoStewnittdhiaremctinuonrcoaumpoluenrtofof `mitochondrial PFOS had not respization in-vitro been demonstrated (6). and Prior to the the relative ctuorxriecnotkisnteudiyc,sodfirePcFt OmSetAabwoelriesmuonfknPoFwnO.SA 0 PMFeOtaSo.disnwseerreumreacnendtllyivveraldiodawtned10fotrhethleoqwupaarritiptaetriobnilolfioPnFlOevSeA{ (a7)n.dIint-svpiovtoensttiuadliemsetwaebroel.itteh,us, warranted to investigate the toxicokinetics of PFOSA. Materials TTnhiteiatlesatnamlaytseirsiablywGasCMidSentdieftieerdmaisnePdertfhlautotrhoe.ocstuarniensgumlaftoenraimaildewa(sPFoOveSrA)9;9%Loptunruem(b8)e.rQLu-al1i0t0a0t9i.ve ainsodmqeurandtiisttartiibvuteicoonmwpaossiatpipornoaxlirmeastuletlsyd6e5r.iv8e%dCfFr3om(C'FH2a)nxd-*SFO2--NNMHR2a(nNaolyrsmiaslrechvaeianl)e,d 1th8a.t7t%he rinetveeranlaeldmloonwo-lmeevtehlyi!mpburraintcihesaonfd 11.2% Isopropyl 9,600 ppm PFOS branch (9). HPLC/MS characterization (0.96 %), and lower concentrationsof several o1tgh/emrla(m0i.d2e5s%(o1f0).thPeenrfolmuionraolosdtoasneo)at(1e2)(.PBOaAsAe)d woansthfeousrudmiorfthtehedoirsaipnugritsioelsu,titohne apturaiteyveolf tohfe.2.5 PFOSA sample was determined to be approximately 96% (8,9 & 10). Methods The protocol (11) and analytical methods (12) used in thi study ave briefly described below. Dose and Dosing Procedures: rAatssi(nogblteaSimnegd/kfgrodmosHearolfaPn FLaObSorAatwoarsieasd)mionnidsateyrzeedrovoiafotrhael gavage study. to 15 male Sprague Dawley The PFOSA was preparaesd a w1e%ig(h1tmwga/smla)dmuinniifsotrermesdutsopecnascihonrati.n 2Th%eTvweehiecnle80c.ontArovloglruomuep,ocfo$nsmiistsiunsgpoefns1i5omne/lkegSbpordaygue Dawley rats at2 volume o(aflSsomioibktaginoenddfaryozmerHoaorfltahneLasbtourdayt.ories), received 29% Tween 80 in deionized water Page3of18 T37M1S5t2atgPiFcOTSoxAicPoKlosguydSyTn39as Specimen Collection: osUanrcirdniaefyiascne1do, n4f,edcaaenysd2c2o9l9pleopcoststitodndososseweegrraoenudpm.gardFoeisvs0e3naedncairymosapls1sy~wf4arsopmopscetarcfdohorsdmeoedsf.erogmrSoetuhrpeaawnnedirmelaielvuesrtdhwaeensriiezgeacdotlebldyucfCtoOerd; from cach animal and flash-frozen in liquid nitrogen. Specimen Handling: wPSepAreDec,iamn3eanlMsyzE(enudrviibnryeo,3nfmMeecneEtsn,avlliirTveoernc,mhaennnotdlaoslgeyfrouarmn)tdhweSeaprafereermnatSiecnrtovamiicpneoesdu, nfadtor-aa7nn0dalmCyestiasan.bdoLlsiievtneetsr.tao nTKdisserHaasnasmepnl,es ffdooerrtePpcotOsisoSinbl(weeLfrOuetDu8)r.e4f5aonrnagPlyiFsmiOlsSiaAnslawipevperrreopar3ni.da5t1ne..g7/4mnigi/nmtiheinlitvheersaenrda 1(1.25),ngU/rminleianntdhefescereahs.ewTelhriemeitLrseOroDafisned Results Control Groups: Body and Liver Weigh TiTohhedesaneavr&earpsaogsletosidtnoiastniea,lavtbheeroadagyveewrofeagieg2hb.2 ogxdybSoDwdoeyfigtwhehtiegghfatiinfriwoeanmsvde2ha4iy.c2zleercoaontnodtodrlaoymma1 ldpeaoysrtaztdsearswoea.1s0 2F7r3o.m7 2da7y.3z6r0 wdoesieg.htbopderycweentiagghetsianrceresahsoedwnanianvTearbalgee of 114.1 14, g. Liver weights and relative day liver t 29 pose body CLiovnetroalnadnSiemraalsCohnacdenntoradetcieocntsable this study (data rot shown). levels of PFOSA or PFOS in liver or sera at any timeduring PFOSA Dose Groups: Bods and Liver Weight TiTphhedesaaeyvre4artpasogsLetosidtnoiastniea,lavtbheoerdaaygveewreoafi4gg.eht5bg=ocSbyoDwodefyitgwhheteiggfhaitifntferwenoamsPdF2a0Oy.S0zAerdonodseddframoyaml|edpaorysattsdwosaes. 27F0r.o0m%d3a.6y ecoro woesieg.htbopderycweentiagghetsiwncerreeaseeqduiavnalaevnetratogecoonftr1o0l0v9algu.esLi(vTearblweei1g8h)ts and zero relative to dey liver 10 29 post boy, iver and Sera Concentrations PanRdOsSerAaalnedvePlsRoOfSPwFeOrSeAdewteercetehdiignhetsht alinvedrayan|dpsoestaodfosaellaanndidmraolsppdeodsesdigwniiftihcaPnFtOlySbAe.twLeievner : Page dof 18 : 3T-M71S5m2a2ugPiFcOTSoAxicPoKlosgyySTi3n9ras fdiavyesr c1oanncden4trpaotsitondsosoef aPnFdOaSgAaidnebcreetawseeednfdraoyms a4papnrdox2i9maptoesltydo7s.e0 (pTpamblteos32.7anpdp3)m. tTohe0.a1veprpagme ifnrothmedlaiyvser1w1a0s4,ca1l0cu2l9atpeodstfrdoosme,a lroegspleicnteiavrelryeg(rTeasbslieon2o).ftThheelhiavlefr-lPifFeOoSfAelciomnicneanttiroantoifonPsFtOoSbAe. n5g2/mdla)yso.n Tdhayesse1,ra4,coanncden2t9raptoisotndsoosfe,PrFeOspSeActiwveerley 0(.T3ab%le0.31).pTphme, h0a.l1f-li0f.0e ofzenldim<iLnaOtDio(n1.o7f4 APvFeOzSagAeiPnFtOheSlsievreurmancadnnsoetrableevceallscupleaatkeeddfroonmdtaisy4daptoas,t bduotseisaensdtidmeactleidnetdo bbye dleasys2t9hapnos4tddayoss.e ftorolmow2e8r.2l.e2ve6l.s1tphapnmfoonunddayon1 dpaoystondeo.seAv(e0r3a7.g4 e=2 3S.D6 plipvemr oPnFOdaSyl4evpeolsstidnocsree.aseLdevseilgsnitfhiecanntly dveaclrueesasweedresiagnpipfriocxanitmlayte10ly23$.8pp=m4.o1npdpamy by day 29 1 and day post dose (Table 4 post dose, ther, 2). Average sera PFOS decreased significantly to approximately 4.6 ppm on day 29 post dose (Table 3). ver and Sera Concentrations as a Percentage of Dose dTohseepaetr$ce.n4t%agaendof0P.F2O%SrAespdeocstievdeldye.tecBtyeddaasy P4FpOosS:Adoisne.thethleisveerleavnedlssehraadpderaokpepdedontoda3y.2o%neanpdost 00.00%%(aTnadblbey6d).ay 29 post dose the liver levels dropped 10 0.1 % and the sera levels remained at #Theonpedracyen1tpPosFtOdSoseequainvdaliennctrsedaossededt0de3t2e.c3te%daansdP6F.O0S% biyn tdhaeyli4veprosatnddossee.re wOansd2a2y.209%paonsdt d5o.s2e, these could laecvceolsunhsadfodrro3p5p%e,d2t.o5%2.5.a2n%d a5n.d6%4.o1f%,threePspFeOctSivfeoluyn(dTaibnlseer6a),. Residual and 3.6%, PFOS 2.7%, in the dose and 3.9 % of the PFOS found in liver on days 1,4, and 29 post dose, respectively (Tables 4 and 5). p"Tohasetnpddeors5cee3ntt%hePseFdOlaeSyvee|lqsupdioevscatlrdeeonastseseddaon1s0de2id5n.cd4reie%cacsteaedaddtoa4s.315P.F%4O%iSn aetqnhudeivl6ia.vl0ee%rnatsnbdyinsdetarhyae4rleipvsoepsretcatdniodvseesl.eyr(aOTwnaabdlsae2y67)2.29 Sera POAA Concentrations osPnaemrdfpallyuesosr1oionactnthdaen&cPapFtoeOstS(-APdOodsAoeAsr)eesgwpraeocstuipfveocluoyn.ndtaTaihtneaesdleePvveOallAsoAefsaet2q.5 aunvagle/rm3aig0e.i8nv%atlhaueneddsoo2si3fn.g50.1s%oalnruedtsip0oe.nc8t(i1pv2ep)l.my,SPeOraAA POAA dosed (Table 7). ofthe Conclusions: Nraoticosoumnpdoeurntdreraetlmaetnedt ecfofnedcittsiownesr.e observed on body weighs. iver weight, or liver/body weight BfooltlhowPiFngOSanAoarnalddPosFeO. SAwpeprreoxfiomuantdealtyh3ig8h%ocfontcheentPatFiOoSnsAidnotsheedlwivaesr caonndvseerctaedoftoraPtsFoOnSe fdoayu.r Page sof 18 T3-M71S3a2t2egPiFcOTSoxAicPoKlosgtyudSyTi3n9ras PodfaFyaOspSpprowsoatxs-idmofasoteue.nldyPiR5.2nOtShdeAaylsli,evveaeralnsndddaimsmeiurncaihsahseahdlolrittneirbmoertephsoisidenertnascaetnhpadenrlwiivoeedrreionpvrteehrestesinemtrea,i.nwtSihiteghndiaofsiiecv,aenrtthlheyarlemff-oolrriefee nPmoeFttOadbSeotAleirtcmoicnPoenOdv.AerANsoiwoagnsluofcfouPuronFndOiSidneAtohtriosoPtsthFueOdryS.cooTncjhcueugrarrtoeeudst.eowNeforeedliiarmneiacntlayetzvieioddneofnofrc,ePafFnodOr SmfueArttaihnbeorthliiinssvsemtsotuidfgyawtiaosn wofaspoeslsiimbilneactoendjtuhgraotuegshinthteheluunrginveiaanedxpfiercaetsioins,wbaurtratnhtiesdh.asIt nsotpboseseinbldeettehratmisnoemd.eoTfhtehperePsRenOtSA rreessuullttsinsguPggFeOstS that the PFOSA is accumulated from in the the dose liver. is progressively converted to PFOS and that the Page sor 18 3T7M15S2e.a2egPiFeOTSoxAicPoKlsoagydSyTmI9rt Report Prepared by: Signatures Deanna Luebker, M Advanced Research Toxicologist Andrew M. Seacat, Ph.D. Toxicology Specialist ) Lac? Report Reviewed by: Fon 2. Bieatray JSeonhinorL. LBaubtoernahtoofrfy,MPahn.zDg.,erDABT, CIH { 200 Date oif1e]for Date 26 TH of Date Page of 18 10 T37M1S32m2ePgROTSoAxicPoKlorguydSyTnI9as References: J. rGaantrso.esvMsa.lmSua.antiTMohneRs.oifsd,iasnUtdnriiBvbo.uwtoiefonnG.eJoeMrlg.iimai(n,1a9At9ti0oh)ne,nTsia,snsdGuApe.oatne(analtlyissaoilspfooosfrsfilbbuilooyraicpncuabutlmeiudslhasetudiloafnso: nnGamroiordasleslympeaesntxipfcoiadsree:kd pR.estaincdidBeoinwceatns. JF.Mu.n(d1a9m9.0)ATppils.suTeodxiicsotlr,ibubtuitonnoatndfoeulnidm)inationof a fluorinated sulfonamide 2 aGnrdosasfmeranprMoRlo.ngMeidsdpiaegtealr,y eMxEpo.suarned Food Chem, 40, 2505 - 2509. tBooawheinghLlMy.Au(o1r9i9n2a)teDdissturlifbountaimonidaendpetsitsiscuiedein Jr.aAtsgrdiucr.ing 3. L6M2uC9lM2v,Sa/TnM-a6SD2..9E3.A,nTaanl-yd6t2Hi9ce4anliaoRnendpoJT.r-t61:9299965.6AbQyDuaErlaMittOaa1ntidv3ehMui,nmvaAednstvhiaegnapctaietoodncyBotifeotashnueasliiynnt-givciiatolrnoSsmeprervtiaacybeoLsl,CiAnsMcmoSfaTn-d 43pp. 4. S2Penomdoin-Tq-Gu6aK2n,9t4iLtfeotrwiovemesraa.ntaal1ny9ds9i8sh.uomfAdaTdn-i6th2ie9opn5aatliocCyrhtaatersaacnbtdyerhTiuuzrmabtaoinolnohoenfpSampterotacayybtLoelCsi/tiMensScoubafantdTe-dL62Ow9iM2t,hSAT1-.S66,226923, BTi-o6a2n9a3lytaincdalT-S6er2v9i4cebsy, LInOc.MS69/pMp.S. Analytical Report: 96AGKPO1.3M, Advanced $: SPeearcfaltuoArMoo,ctaTnheosmslffoorndamiPdJo.EHthaannsoelnTKo.Jx.icainydiBnuRteesn.ho(fifn pJ.rLe.paSruatbi-oCnh,ro8n/i1e1D/i20e0t0a)ryN-Eibyl 6 UDWnlaiolvelenarecsreigteKyd.Bio.sf MoafrnNdatSStciahvroekosolmvoifAt.oMceh1do9i9nc8d,irnieTa..heDDueepfltfu.etcoht,foMfBNipeorc5fh5le8um1oi2rsi,tnraUtySeAad.nadrSyMulopalpteokcryutllesadurlbfByoinoaalmgoigodyue,ss ofnrom 3M Company 7. CKhJa.raHcatnersiezna,tiLo.An.ofClOergmaenni,cMFEl.uotEolclhefesmoinc,alHsO.in Environmental Lab, S. Paul, MN $5133 JGoehnnesroanl. P(o1p9u9l9a)tioCnoHmapmoaunndSeSrpaecSiafmipcles. 3M 8 PRaeypfoerrt R9/M2.4/9G9.C/5MMSSanAalCysiLsaobfBPuiFlOdSiAng(2L3-61-0200B9.)1.1 SAC Analytical Request No. 59426. 9. /TSpSoeMmcMtDrK-eos2stc3no6epr-y.2R8Ce-hqe1um1eis,ctasSle#pCt5he9a4mr2ab6ce.trer32i5Mz,atS1ip9oe9nc.ioafltPyFAOdShAe,siLv-e1s0&009C,hebmyic1aHlsanAdna1ly9tFi-caNlMLRaboratory 10. 2RD0ee1qR1uo-eo2ss9t,sF.CLA.-A1CT5h1Ca2r5a-4c.CtehrrRioezmapatotirootngs1oa0fp7Ph9Fy9O.GSrCAoourSppaomrpalteesA,naTl-y7t1i3c2a-]1T(eLc-h1n0o0l0o9g)y aCnedntTeNr-,AB-u1i5l8d4i.ng Page Bof 18 n 377M1S3t2ra2tegPiFcOTSoxAicPoKlosgrydSyTi3n9ars. 11. SOeFacPaEt O&SLAucIbNkeRrA.TSP.rot3ocMolMoedricSatludDyeNpoa.rmTe-n7t15,2.C2o;rpSoTr-a3t9e,TPoxHiAcoRloMgAy.COOKctIoNbeErTI19C99.STUDY 12. LinabRoartast(oSreyrRaeaponrdt:LivAenra)l.ytLiacbaolraRtoerypRoeofpoDrratttNao.forFPACFTO-STAO(XT--1714352.(2W)28P1h4a)r.macToesktiinnegtic Study LLaabboorraattoorryy,3FlMuoErnivnierAonnamleynttiaclalTCehcehmniosltorgyyT&eaSma.feLraybSoerravtiocreys,Co3ntMacEtn:viKrroinsmHeanntsaeln, Ph.D. 13. Alman and Dittmer, Blood and Other Body Fluids. FASEB, 1971, ps 2 Page9ofis 721M3S2t.at2egPiFcOTSoxAicPoKlosgydSTi3n9ras Listof Tables: Table 1: Biological Parameters 1A: Control Group 1B: PFOSA Dose Group. Table 2: Liver PFOSA and metabolites in the PFOSA Group. Table 3: Serum PFOSA and metabolites in the PFOSA Group Table 4: Percent Dose: Liver PFOS equivalents in PFOSA Group. Tabl5e: Percent Dose: Serum PFOS equivaleats in PFOSA Group Table 6: Summary: Percent of dose in sera and liver. Table 7: Serum POAA in the PFOSA Group. 3 Page 100f 18 371M5S2r.a2tgPicFOTSoxAicPoKlosgiydSyTi2n9ras [Fable 1A: Biological Parameters. Control Group [Time Dose [anima#|l nial|Terminal|BW Gain] Liver [Liverwias 19R03-xxx| BW (g) | BW (g [[DDayay 11_ CCoonnttrrooll O23301] g2r8a2i5l] p26e2n0al a) | wi(g) | %ofBW Dr5l i1r2a0] aa3s%l) [Day 1_[Control 232 2774] 233 27417 2773] 2748] 031 124] a5 07] 118 42% [Day1[ConTtrol 2342676, 2605] Java TT [Taran _aras 73] Tio, au 22 is] as [[ Pay5a TC0ontrT ol| 2357 ] 2666] 21 884s3] 325 7a6] o16s]6 0351%4] [Day 4_ [Control 236 275.8] [Day a IContol 5572619] 301.8] 2834 260 114 a15 118 3.8%) aay] [7 D[Daayv@e CoCnotnrvoel|| 223380]] 2678950] 3a0szti72] 223287 i07a 3377%] _--| [56 [Day 28 [Control TT" 3 [240] 2735 [Day 29 [Sonar 2412705 80 33870158] 247 oa o2u 11808.0301 114348]] 33.87%%] [D[baayy2255[G[oCnotnrtorre [Gay 29 [Control 242 243 2802] 289.9 S654 asd 002 154.1] Ted] 175 36% 39%) 204] 2663 3652 069 a3 35% [lava TT [Iso T2761] 380.00 32 314 waa] tas 230 15 saul 0.1%) " Pa11gofe18 PayT Smokal [PayTSmaka 2e5T 2632" 246] 664 7578]_ 2552 5a 68 704 102 -- sow au Dart Ismael 248 2672 [PayTISmaka[peo 26871 2640 s6e3] 32 10.4] aa tor 36%) 40%] E [ls T avo aT 7 T 6 20 2361a56 1asgt0o3s5 0so%w [PaysTSmaka [Days Tsmaka 250" 666] 261 272i 2863 25a] Ter 113 pas] tial au ow] [Day& TSmaka [Pay Smakal 250 2717 _2sas 253 2716] asta] 2a0l a1 ros 113 arm ao [Paya TSmama ava | ose pro Trio assess 2510 200 tio 116 atm 40% Par28 Smog] 256 2736 [Pay28Tsmaka[257 271.4" 380.3 1067 tad 5738] f025 a9 35%) 37% [-- PaysSamvoakal72T8ar2e66s7 as57 srs sao Tar fo0s fas aw su] L077 26 ws a7 15 ow - / B SegR TooE S139 eb Ce POST a rrerbore T Tor PROS os iomRaosl-{tiver pros) | Juver prose iver pros ros E[eToimemmea m tm Txw xx ppe m er ppm e -- leq ppm"-- Briar nC ---- -- e se a p r = ------ ------ BBbPaoreliofms mmere [a w we o y 3 Pomr e y ----] ---- BPE o aElpT mr ms T p e -- r s e Eo --ty 1i--] ---- ---- 3 Passeer s--T --)e -- e i--r ti--------m-------- ----1--2] e T==rSoinnimiccsaeTroeaaftrueenSrTroPommFdOooSaReFviSvoe SeseByyosa ns TrSaFrPoReOoSenP)ROS rd er rroms oi POGL= amecnoed saeuaasmoinoimoiraivvr t(rPal= 5paon 1E820) Page 130018 CC TMImSeBrOTSoxAicPoRlogytysTmIts Table 3: Serum PFOSA and metabolites in the PFOSA Group . 7--_R--03: [sera FOS) [sera ROSA) Time xxx ppm ppm SeFr7a0P8rOcaSA ppm' PadlpTs me egre T I w T r o s T s s Ree bor [avm3 c Ts woesrea y x] PPDauoveimTso[ wemmeerss [ m To a a T r i on e l T ----] s --nd [BpooisTBeoT mT emewesg Ta as s 7sT T o o e ms ----r ------u04g]] Rseear fe o4e]] BoiTror Po fmrmeoamnse-- T -- --aT se a --i solca s goonp-- --o ---------- [RuefdsIJsE mmeerkesT 1m mae a3rT -- g] opg (M FFo Em--e-- 1f1eT e T--Ts s S5--|1r s -- --] ------] [[| AsPsAucmRnintgenOt3r1aSitonatoo PFOSA PFO squmatenss ST PR--OSA--FFO--S ca--pmm1ss --3r--f =MO=Lssi=gcnmiaectnantnotydyedetearceteannn fifomom:rs(cyaPyR18vOva=laSutes4s75boyry a2mwwooPtRaeOasSdATT~oas3eet5t0(epr<e0d.n0:050)) Lo=iDri of setcton (PROS = 1.76 nym: BFOSA S182 a Page 140118 7ssFREFE REESE iEx sEaR ssEy HE : gH | EE HE eb L L EEE 3 FEeEaaeEy FEEERE FRET AH ded LLL He 5of5}PEFRR REFERERNE R LH FFARRHEceHdEe: E3 H d] INE $ | H{ (rl | IT] [1 Ese 1111 [gist 5 J 53 FERREEEceRe BAaERaREaREEcet:ec EFEiRseEa| EeTEerlEi2i5Hi5i% | | FT Esse unin Ht [Rae - = 3:2 fBrEEeRRsEAaEsNRcEeEsEA3A n5a3RsSEAREYRN EErEsBsamS umene nn|Ei 1 FreRee fad iesniEd gad TTT TTTng BE EcireSszR ERR R NhR FFE RR RRR i SR Leg 52E 25 |E | |||]| FF[H HFERRh [I11] IIT]g([ge%ag5sasg3eEs8d | Ili] I Jsizs8g H JEHR LEE] FTETT [gssds ig #i008 zaA gelzsle!| |la$B8a2eE2d8E||R1s||| lool ||| (EggRglEslRs |ESly | || [E288 [HFEREE it ie Jr [|][foie||| Fae || Fis /8 iii HLAERARRA i . 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