Document LJ67YQQ7m7z92oODQNJ3m8B1Q
AR226-1898
oT9m515FR
3M MEDICAL DEPARTMENT, CORPORATE TOXICOLOGY
Low
Level
Oral
Perfluorooctanesulfonate (PEOS) Dose Toxicokinetic Study `Serum and Liver PFOS
in
Rats:
DateF:inAaplriRlep1o4r,t2004
Study No. T-6295.15 Strategie Toxicology Study Number: DT-31
Research Client: Sponsor: Study Location: Study Director:
Study Toxicologist.
33MM CSpeenctiearl,tByuCihledimnigca2l3s6Division Saint Paul MN 35133-3220 33MM CSpeenctiearl,tByuCihledimnigca2l3s6Division Saint Paul MN 55133-3220 33MM CSternatteerg,icBuAilltdeirnngat2i7ve0-TSoBx-i1c8o1logy Laboratory Saint Paul, MN 55133-3220 TAonxdirceowloMg.y SSpeeacciaatliPsht.D. 33MM MCeendtiecralBuDielpdt.ing/ C2o0r-p2or6a-t0e2Toxicology P`Sha.int6P5a1u-l5,75M-N316515,13F3A-X3:226031-733-1773 `DAedavnannaceLdueRbekseerarMc.hS Toxicologist 33MM CMeendtiecralBuDielpdt.ing/Co2r2p0o-2rEa-t0e2Toxicology PSahint65Pa1u-l7,37M-N137545,13F3A-X3:226051-733-1773
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S"Tuhimsmsaturdyy was done to generate Kinetic data on Perfluorooctanesulfonate (PFOS) in ats ainndthfeelmoalwedSopserargaunege-,Dawwhliecyh rcaotuslwdebreeogfivvaelnuseinignlethoerailsdkoassessoesfsm3,ent10,pr3o,ce1d0u0r,e.orM5a0l0e0 ahngd/KtghiPrFcOoSrr(eNs=poSnidsienxg/dvoesheicglreocuopnltiromlegproionutp).anTihmeal3s,(1N0,=S3/0saenxdi1m0e0 gpo/iKnte) wdeorsee groups scaocmreisfipcoenddoinngdavyeshi1cl,e4 caonndtr1o4l pgorsotudposaen.imaTlhse(5N0=030/suegx/Kiemedopsoeingt)rowuepreansimaaclsifancdeotdnheir ldeavyesls1,at4,ne1c4roapnsdy.28 post-dose. Serum and liver wers collected fo analysisof BFOS a"Tnhdetfiemmealpoeinrtast.s gTehneermalalxyibmaudmhisgehreurmsePrFuOmSPcFoOncSenltervaeltsiotnhainntthhee cmoanltersolinanlilmdalossewagrso6u0ps cnogn/cmeLn.traTthieonlsoowfdSo0sensg(/3,L10inafnedma3l0eprga/tKgg)ivreensult3e0duing/mKagxdiomseu,mesqeuirvuamlePnFtOtSo control pvaplbueisn. feTmhaele10r0atsugo/ndKsaydo4speogstr-oduopshea,danmdax1i20mupmpbsienrummalPeFrOatSs oconndceanytr1a4tipoonsstodfos2e0.0The, 5000 ug/Ke dose group had maximum serum concentations of15.85 8.00 ppm (12% oSfedrousmeP) FinOSfheamlafl.esiaenodf 1c3l.i3m6in+at2i.o5n6 w(a~s9e%stoifmdaotesde)frionmmtahleesteornmidnaaly eolniemipnoastt-idoonser.ate The constant to be 16 days in femal rats and 14 days in male at, `STihgenimfaiclaentraisnchraedasheisgihnerivievrerPcFoOnScencotnrcaetnitornasotifonBsFcOoSmptahranedfetomacloenstaotlavlaltuiemseopcoicnutrsr.ed in th 10. 30 and 100 ug/Ke dose group males and in the 100 ug/Ks dose group females. 3"T0he0a4v0eruaggeg=rSanDgeliivnerboPtFhOmSaclosncaenntdrfaetmiaonlsesfowritthhen5o0s0i0gnjifgi/cKangtddoisfefegrreonucepss awtearneyintitnh.e Liver PFOS concentration half-livesof elimination were determined to be 18 and 24 days mfoarxtihemumamleliv1e0r0PuFgO/SKscoanncdentthreatfieomnasleanSd00li0veurgP/FKgOSdocsoencgernoturpast,iornesapercetaisveulnyd.erTthhee curve t(hAeUmCaSl)ewreatrseagnrdeaitnerthteha3n0tuhg/cKoentdroolsevgarlouuepianntdheab1o0vueg/foKrgthdeosfeemgarloeupratasn. dLsivbeorve10for rsaenrguemdPfRrOomS2c:o1nc0ent11r:ativoenrrattiiomes.inItnheco3n0truags/tKhgeanlidve5r0000siegr/uKmePdFoOsSe gcornocuepnstrwaetrieon draetciroesaisnetihnem1a0l0esg/ovKeerdtoimsee. group variedfrom 5:1 t0 52: and increased in females and o`fThaepsperroexsiumltasteslhyow14t-h1a6tdPaFyOsSingmiavleneaatn0d0f0emyalge/Kragts,hraesspaescteirvuemly,bwahlicihoafreelimination aelpipmrionxaitmiaotnefloyr2m-afloeldgrartesatdeorstehdawnitthheanpreeqvuiiovuaslleyntreopsoretoedfse*CrulmabPeFlOedSPhFaOlSF.-ife of
4
EE
ae of ['"CJFC-95 (mean dose 4.2 mg/kg) administered to male rats was absorbed within 24
, not metabolized, and the plasma elimination half-life of /C was 7-5 days (Johnson and
dosesof5000 mg/kg (O'Malley and Ebbens 1980),butnot necessarily at a very low dose
(Johnson 1995). Single i.v. doses (mean 4.2 mg/kg) of ['/CIFC-95 in 0.9% NaCl were `administered to male rats. By 89 days after dosing, 30.2%ofthe administered `C had 1979). Fecal and total excretion of '`C were markedly increased in male rats administered
cholestyramine (~ 2.7 gkg/d) in their diet following single i.v. dosesof ["CJFC-95. The
al. 1980; Johnson ef al. 1984).
Sema
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SaAltm(ge/rmflLvrsotooccaknscosluultifoonnoaftepe,rPflFuOoSr,ooCcAtSane#2s7ul9f5o-n3i9c.a3c,id,CpioFt0asSs0i5umK') in 2% Tween 5p0erwfaosrmperdeptoarreedacihmmtehdeiaaptperloyprpiarteico0ondcoesnitnrga.tiSoenrifaolredaicthiodnossoeflehveel ssoucchktshoaltuatisoinngwlaes doreaslirgeadvdaogsee.doDseosveoslwuemreeoafdmimnlisdtoesriendgvsioalourtailognavkaggbeotdoyawiesioghntdwaoyu2l6d10deolfitvhere tshteudy. "DTohseedoSseelsecsteilonecJiudsftoifihcastiolno:w dose POS study were designed to yield serum PFOS (lpepvbe)l.sthBaatsaerdeoant porrenveiaorusthdeatlai,mit|omfgqoufanitnigfeisctateidonPRofOaSpypireolxdiemdataeplpyro1x5impaatretlype$rpbiplmlion yPiRelOdSaibnoutthe1b5lopodb. PTFhOerSefionrteh,eubslionogd.linTehatreesxtucagpoglatwiaosn,h3uspgseklgecwteodulads tthheeolroetwicdaolsley. MAethheoddesoifgSnaatmepdletimCeosl,leacntiimoanlsanwderAenaeluytshiasn:ized by CO; nd gross necropsy performed. Dcuarnisnfgrnredcrtoopbslyo,osdysctolelmeicctibolnootdub(e=s wimtlh)ouwtasanctoilcloeacgtueldanvtiaatnahdbadlolmowiendaolcslootrto,ra npeirnieosd.of T1h5etos3e0rumminwuatsestraatnrsofeormedtetmopelarbaetluerde 1t.h5enmlcemnitcrrioffuguegdeatub1e1s0a0ndgcefnotrrifuged gpoaliynpraotp2y0l0e0nextugbteos raenmdofvaesahnfyrorzeemnaiinnilnigquriedd ibwlooogdenc.llL,ivterrasnswfeerrreedre1molvaebdel,ewdeighed, pTlvaecresdaimnpdlievsidwuealrleysitnotroedlaibnelaefdrbeeezesr asentdtoflmaasihnftraoinze-6i0n1l0iq8ui0dnCittrhogeenn.pacSkeerduminadnrdy ice aannadlysshiisp.pCeedrtaoinKrliisveHrasnasmepnl,es3wMerEenvfiurrotnhemrenstenatl(T0eacnhdnoalnoaglyyzaenddfSoarfPeFtyOSSercvoincceesntfroartion ObhyioB)a,tcTlhee aLnaabloyrtaitcoarlimesetfhorodPsFuOsSedcownecrenetrcaqtuiiovnl.en(tBattotetlhleemLeatbhoroadtsorrieepso,rtCeodluelmsbeuwsh,ere (fiHlaenfsoernmaetf aflr.o2m00t1h)e.3MReEsnuvlisrownemreenrtaelpoarbtaetnoddathea3lMteMredriecpaorltdceopnatratimneinntg iivearnPEFxcOeSl adartcahifvreodmbByatttheell3e.MAEnfviinarlonanmaelnyttaiclalLarbepaosrtFwAaCsTnoPtroijsescuteNdo.a:nd TthOeXpr1i0m7aroyndOactatowbeerre8, 2003 "ATnhaelaysviesroagfetsheerDuamtPaFOS values used for the satisical analyses and for the gneonnecroamtpeadrbtymesnutbastliatuntailoynsoefso(nNeC-AhoantlhWefinlNimointloifnqusaonfttiwtaartei,o(n N(iC.eALMOoQd/e2l=2000.)00w2e7r5e eguimnPfForOSs)erfoum aPlFlOsSa)mpolresonheathawlefrtehbleilmoitwotfhodesteelcitmiiotns,(iLnOoDr/d2er=(00.co0n0v0e8r9tgt/hemLn.onf-or numeric endpoint nto numeric values. iNnotnecropomlpaatriotnmetnotianltepgraartaemettheerdsatwa.ereWeisntiNmoantleidnuessitinamgatleidnetahetrraatpeezcooindsatlanrtu,lei,wiatshsolciinaeatred
.
wwJieatrsheftoehuxret,rtaefprvomlianptaoelidenoliimeiincfn,iantiwitiyot.nhpWnhioanns-eN,zoenrIfolcncoornuecpleendattrbsaterieeognsesi.smsaPitooeindns,tsutshpeirncigalttchouelCaamtteadxtphwarereear,metehtneeankrsthe sdTeeugdsr.etsesTdihoRenErwedigotrhcessthsneiolotnairwmgipertonvtuehm,ebbleuarrtgoesfstpwoiaitdnjhtuissnt0we.da0sR00*u1swdao.fstsJheelemlcautrsegtde,sbtweiapdtojhustsihtteeesde,Rca'anvvdeaalctuasel:,cutIlhftaetheed rnaotmuraatleoagatritthhrmeodattfha pcootnsc.entWraitniNononvalliueesstinimtahtiseda1n.gbeyopnersfaomrpmliinnggatirmeeg.ressiisondeoffintehde 25:7, 1 estimated lop. "wCToehnievgehorsas.lioaTnfmhaoecutonottraloofPaf F32mO.3SomoLiunntoPnfhFesOteiSrvueimrnpwteahrseKscgealrbcuoumldawytawesdeibcgaaslhcetudilnaottnehdmeebaaatssue(rdAeoldnmlaiavnearnd Dittmer 1971),
Results:
B"iTohleorgiwcaasl nPoareaffmeectteorfseament on body weight (BW) oliver weight (LW) (Table 1; IndivanidSdumumaarly daa ae in Append 1).
S"dTeohreeuflmeemvePallFse,OrTSahtegeanveerraalgleysbeardahPiFgOheSrcsoenrcaePntFrOatSiocnosnwceenrterabteiloonswtthhaenLtOheQmafolresretrsuma.t all.
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t1h3.3w6e+re25si6g,ni3f9ica%notlfy hdiogshee)r(iTnafbelmeal2esAp(p18e.n88d-i+x 6).00Fepmpaml,e1s29u%omfPdFosOeS) cthoannceinntmaatloenss
wi"Aneptrpheensid1gi0nx,i3f60i),.caT1nt0hl0eyaohntihdgeh5re0rt0ih0maeungpo/tihKneetmsdaeolsreeesgernrooutumpasnPbaFlyOyzDSeudcnonfneocrtetnst'igrtnaitefisiotcnasmnteotndhidfofadeyr(eopnn<ce0e.ps0ob5s,ettdwoeseen
-
`male and female serum PROS concentrations.
SDitnuanbtinostcthtic'masalllyeessaitgnndmiffieecmaantlteitnhaocctroeonaotsrnedosyliinvnasltehureeus1m(0P0LFOuOgGS/?Kcgoorn(cTLeaOnbtDlreIa2t3i)soaunbnssdctio5tm0up0tea0druevgda/lbuKeyest)(htoetcicsutrirceadl mSaaniiyfscaentnolty sdihfofwenre)ntdomseeagnrsoufprsomathael ctoinmteoplogtarso.upDumnenaentt('Dsunensetttw1s964u)s.edI0ndidveitdeuramline pEoariovnilsyeacnomipndairviisdounasl ucsoimnpgarSitsuodne.nTtsheseestruwmerePaFlOsoS ccoomnpcuetnetda.tiSotnudfeorntthseefsetmaislesi3z0ed uy/ssondeoasndgrfoouup pwoesrte-dSoigsn,ifdiecmaonntslytrgarteiatnegrtthheadnitfhfereconncteroiln vsaelruuemsPbFyOSStucdoenncte'nsttreatsitoonn Tesponse between genders at that dose level (Table 3, Appendix 6).
,
"aTthse ialvluestrraatge+ethSeDcosnetrrausmtPbFeoOwSeevnertshues5t0i0me0 ggra/phgs dfoorsefegmraoluep(aFingd. t1h)ealnodkemraldoes(eFgirgo2u)ps. "gTrhoeuapvsefroargfee+maSlDe (sFeirg.um3)PaFnOdSmavelresu(sFitgi4m)eagrtapchosntfroarstths m0a,l3e,s1e0ruamndPF10O0Sig/Ke dose C1o0n0cegnt/rKateiodnoss,ewhiatdh sfeermaulmePsFeOruSmcPonFcOenStrlaetvieolnsnthtahtatadpopseearaendgoe.beThinecmreaalseisnggiatvetnhtheend oafdthseer14u-mdPayFOobSsecrovnacteinotnrapteiroionds.thIant cdoenctrreaasst,edtohveefretmhaelle4radsaygiovbesnertvhaeti1o0n0puegr/ioKde dose Individual sera PFOS data ace shown in Appendix 2. W"TihneNvoenrlaigneS+erSaDPsFeOruSmNPoFnOcSomvpsatrimmeenwtearel palnaoltyesdisin sparate graphs for ach dose g(rAopuppenadnidxg3e)n.deTrheusaivnegraWgienNsoenrluimnPNFoOnScovmaplauretsmuesnetdaflo AntahleyNsiCsA(NwCeAr)e,gMenoedrealte2d0b0y Shuebsltimaittioofnodefteocnteiohnal(fLtOheDIl2im=it0o.fq0u0a0n8t9itga/timon)(fLoOrQaUll2s=am0p.l0e0s27th5atgwienre)beolroownet-hhoaslef limits, in order to convert the non-numeric endpoint nto numeric values. "fTohretahveefreamgaelemadoxsiemgurmouspesruomf 1P0FuOgS/cKogncaenndtrhiagthieorn,(aCnmdaoxn)doasycur14refod onthdeamyal1epsositn-tdhoese 100 7K dose group and day 1 for the S000 Kg dose group or both genders (Table 9. T1h6edaayvserfaogrefsemearluemaPtFs,OSanhda1l4f.diafyesoffeolritmhienamtailoen a(t1s,,_gLivaemnbSd0a0_0zp)gw/aKse e(sTaibmlaete4)d. tTohbee 2o1t-dcaoynsseirduemrebdalcEoimfpeleofteelliymrienlaitabiloenhdearilvfedoffoeltihmeifneamtaiolne e3s0tiKmatee gidvoesnetghraotutphewraes wSearmeedceotneccetnatbrlaetiPoFnOaSngvea,luheoswienvseormiet mofatyhehacvoentsroolmegrmoeurpitsegirvuemnstahmapallestthhetswameprleeisnhtahde SapeprruomxiPmFaOteSlyva8ludeasysabdoevreivtehdefLoOrQt.heT3hueg/sKhogrtgerroauplFweirveseoxfcleuldiemdinbaetciaounsoefthe LOQI2 SOufbsPtFiOtSutiionnsthhacdobneteonlusesrdumi.n those calculations, and the values were equivalent 0 levels LLiivveerrsPaFmpOlSes were analyzed at two diffrent laboratories underdiffrent standard curves dwoisthe-dgirfoeurpesntonlidmaitys 1o4fqupaonstti-fdiocsaetwioenr.e Tanhaelycoznetdroatl t(hgero3uMp1E)n.v3i,ro1n0,me3n0taalndLa1b00wigt/hKasn LanQ4dopfo1s0tdnogs.e weTrheeacnoanltyrzoled(gatrotuhpe B1)a,t3l,l1e0,L3a0bswnidth1a0n0uLgO/Qgodfo13s4en-g.groOonnuddapayysss 1| aanndL4OpQoosft-d.o8s8,ntgh/egcoanntdrooln(dgaroyusp164)aanndd25800po0sut-gd/oKseedtohseey gwreoruepasnwaelryzeeadnwailtyhzeadnwLitOhQ of 37 ng/g at the 3M Environmental Lab
s
TlihveerlPivFerOSPFiOn Sthceomnacjeonrtirtaytioofnbso(thg/tmheL)mawleeraenbdefleomwaltheeraltismiitnotfhqeucaonnttioalioannd(3LOKQ)gfor doonseepgorsotudpossean(dTawbelree5b;eIlnodwivtihdeuaLl dOataininfeAmpapleendraitxs a4t.thTeh1e0auvge/rKaggedloisveelrePvFelOoSnvadlauyes wgreoruepsc,onasnisdteinntally hfiegmhaelresthiannthtehe3L0OuQg/iKngalalndmahligsheirn dtohese10gruougp/sK.e Tahnde hpiegrhceerntdoosfePFOS dbeosheidghtehratiwnathseplroesweenrtdionstehgerloiuvpesr.raTnhgeedbafcrkogmro1u8n%dtl0iv2e4r4P%OSof tlehveedlossfeouanndd itnetnhdeed to caonndtr1o0l4gnrgo/ugpianntimwaolosuatvoefra27gedfe4m0alneg/cgonitnrotlworatoultiovefrs2a2namlaylzeedc.onItroslhoruatldlbiveersnoaneadlytzhaetd istvaenodfartdhecumravleethcaotnhrald alilviermsiaonfdqtuannoifftchaetifoenmoafle1c3o4nntrgo laivenrs wtehrtethaenaoltyhzeredIuvenrdser a `liwveerrePanRaOlSyzceodncatenmturacthiolnoswdeerrliivmeidtsforfomqutahnteisfuicbasttiiotnu.tioTnhoerfetfhoereL,OtQh /2avvearlaugeesbfaocrktghreoseund sdeatmepclteesd minatyhboseeailifviecrisaalmlyplheisgh(Aapndpleonrdisxom6)e. baTckhgerporuensdenPcFeoOfSthmeaybanoctkghraovuenbdePeFnOS. m3auyg/Kheagvedocsoentgrriobuutpemdatlhee aravtse.raNgeonofe2o7fthe8ot9h%erodfodsoesgerofuopunshdaindtahne laivveerraogergtrwaotoefrththean 8363%2 o1f2th%eidnofsemainlteh ratlsi,vear.ndT5h5e+o2ve0r%allianvmearlageeratS, Dexpcelrucdeinntgotfhdeo3seugin/tKhedloisveergwraousp `male rat results Maavleersahga+edShDighlievrerliPveFrOcSonccoenncternattriaotnisoonfvPerFsOusSttihmaengfreampahlsesfaor tahlle i0,m3e, p1o0i,nt3s0.aTnhde100 wclge/aKredodsoes-eregsrpoounpsseorneldaatyiosns1h,i4paanbdov1e4tphoest3-0dopsge/(KFgigduorseesl5ev-el9. rTehspeecltiivverelPy)OsShow a caopnpcreonxtirmaattieolnysfo1.0 tphpem1i0n0tuhegfKemeadloesseagnrdou1p.5wpepremhiintghheestmaolnesd.ay 1 post dose and were Sinigtnhiefi1c0a,nt30inacnrdea1s0es0 iungl/iKvserdPoFseOSgrcoounpcemnatlreastiaonnds cin othem1p00atuogcr/oKneetoddlosvealgureosupocfceumrarleeds w(Ahpepnentdheix106)0. uTgh/eKgavaenrdagleow+eSrdDoslievegrrPoFupOsSwceorneceanntarlaytzieodnsacfroorstsheall50i0m0eppgo/iKntgsdose scornosuipdseoranbdleayosve1r,l4a,p1b4etawnede2n8ptohestmadloesseawnedrfeeminaltehse 3at0m0os4t0tgim/egporianntgse(aFnidgusrheo1w0)e.d The 5c0o0m0paurged/Ktodtohseecognrtoruopl lliivveerr PvaFlOueSscaonndcewnetrraetithoenrsewfoerreencootnasniadleyrzeeddtobybeavDeurnynheitg"hest mPeFtOhSodcofnocrecnotrmaptairoinssowneorecaonnatloylzeldivfeorrPcFhOanSgevasluoevse.r tTihmee,5a0n0d0nuog/siKggnidfoiscaentgrdoiufpfelrievnecres bwyeraeSftouudnedntisnLtehset.livers ofmal or female ats rated with 5000 ug/Kg PFOS at any time "WTihneNaovnelraigneL=ivSeDr lPiFveOrSPFNOoSnccoomncpeanrttramteinotnavlsatniamleysgirsaphs were plotted in separate sraphs for each dose group and gender using WinNonlin NCA, Model 200 (Appendix 5).
5
s"Tuhbesaivtetraogneofliovenr PhaRlOfSthvealiuneistuosfedqufaonrtitthaetiNoCnAfrinaWlisnaNmopnlleisnhwaetrweegreenberealtoewdtbhye LOQ g"Trhoeupmsaofm10auigvgeraPnFdOhSigchoenrce(nTtarbalteio6)n,(LCivmear,PRuOgSg)cownacsenotnradtioa4n ohyarlf1-l4ivfeosr omfost dose m50i0n0atpioKn wdeorseedgertouepmsi,nreedspteoctbievel1y8.and 24 days for the male 100 ug/Kg and the female d"aTyhe"uligviernPL)ROwSerCeigmraaatne tahraenatuhnedceorntPrFolOvSalcuoensceinntctahti1o0n uvegr/sKugsdtoismee cgurrovuepsa(nAdUaCbo,ve vfaolrutehse imnatlheea3s0.ugT/hKeg idovsre PgrFoOuSp AanUdCasbowveereforcthonsisfteenmtallyerraet.teLitvhearnPtFhOeScoCnmroalx and a{hreaatreeatuhanndetrhehceoncturrovleinatma1l00eua/nKdsfdemoasle grartos,upFewspeerceivseplpy.roximaely 10 and 15 fold TPahretiitvieorntboestewreuemnPlFivOerSacnodncsenetrruamt.ion (ug/g ugmL) ratios exhibited a wide range of avanlugees ofvreroamll2,1d0ep1 enadnidngreomnadionesde (rTelaabtlieve6l).y stLaibvleerv0ersetrhuemfPllFOtiSmecocnocuernsteraotftihoneistousdy iconntcheent3r0atuiogngaianod n5t00h0eu1g00/gpdKosedgorsouepgs.rouIpn cvaorniterdasftotmh li1ver520asnedraupmpePaFrOeSd.fo oibfnPecsrEeeOasoSeniainncttoihnmeveesirensrifuoemnmaaflncedtsoiavonedrfdweecrr3e2.e3macsaLelcisunelrattuiemmdepfiernrotmkhietlhmoeagilrsaemssu(oefTbaPobFldOeyS6)w.ceoinTgchheetnrtnoatttahileoanmasto,unt and on the actual iver weights. The ato ofotal PFOS in liver o tal PFOS in serum i(nngtuhge) iwsassuecson(sAisptpeenntdlyixan4d) proportionally higher than the ratioof PFOS concentrations "DTihsecaunsasliyotnical methodsfo serum and lve PEOS concentration determinations used in hcoinsssitduedryedwqerueabnatsiactaliytvoth+e3s0am%e(aHanpsubelniesrheald. m2e00t1h)o.dsTthhtayvieerladgreesmulattsithstpiwkeere r7e6c%ove1r1ie%s f10o1m12qual1it%y c(odnattaolnostesrhuomwsna)m.plTehsesspviekreadgweimtha2t5i0spipkePrFeOcoSverrainegsedfrformom 3qu%alidty caonnottrtoslhovwaenr).saTmhpelseesesxptirkaecdtiwointehff2i5c0iepncpibesPsFcOSsriamngietdloftarhroemp$u9bl.is1h%ed vtoal1u1e5s f+or the analytical methodsused of95 9%fo sem PFOS and 100 13% for lve PFOS
(Hansen ef al. 2001).
STahmeplleosw (l2evoeluoff 2PF7OcSacdhe)t,emctaeyd hinavleesbsethnanca1u0s%eodfbtyhceonctoanmtionaltgiorno.upTshcurmatsaundsdlivienrthis sftiusdhymewae.reThfartomsoHuarrcleanofLarbaotrahtaodripersevainoduswleyrbeerenisdeeteornmdiineetds ntohatt1dihdanvoetacnonytain baarckigncroonusnidstPenFtOwSitihnsteheriurmsearndumsoormelivoerfh(eLulcvbekrerPFerOalS. v2a0l0u1e).s beiFnugrtbheelromworteh,etlheidtatoaf quantification inthe 3,10 and 30 pg dose groups.
0
"vTahreiosuesrluimmiatnsodflqvueanstaifmipclaetsiownearnedalniamliytzseodfdientsetctsiuonn.dTehedifsfeerraendtatsatawnadsardderciuvrevdesuswiintgh anpgp/rmopLrifaotresloymleowoftLhOeQssoerfuampsparmopxliemsatferloym6tghe/mm.gf/o Kgthdeosmaejgorroiutpy.ofThtehesdtaatnadaorrd3c7urve. `swaimlhplteheseh.igLhievreLrOsaQmpwlaessefmrpolmodyaeyd 1to4 appnrdofprroimsealytbhera$ckmegt/tKhegrdeosspeongsreoufprormasthweere annga/lmyLz.edIun conntardassate,ndtharerdlivceusrsvaemwpiltehsafnraopmprdoapyrsia1taelnydo4wposltimditoosfqeuawnetriefiacnaatliyoznoedfun1d0er `awsatsapnrdoabradbcluyrvleoswirtohm hthieghloLwOesQt doofs1e34grnogu/pg.livVearlduaatbalseetdsaoyn1thaensde ddaayys4pbeocsatudsoesoeftdhaeta choingchenLtOrQat,iopnasrtwiecruleafryoufnrdomintahle fdoesmealgeraoutpslivferrso.m Fduaryth1e4rpmoosrte,dodseeteacniaabllyezeldivuerndPeFrOaS standard curve witha lower lit ofquantification "5T0hengl/owmLdoisnefse(m3a,le10raatnsdg3iv0egn/aK3e0)urge/sKulgtdeodsien,mwaexriemeuqmuivsaelreunmt P0FtOhSe mcoanxcienmturamtisoenrsuomf hPiFgOheSrcsoenrcuenmtlreavteilosntihnanthtehceomnatloelsainailmladlososfe6g0ronugp/smLa.ndTthimeefpeominatls rats generaly had "sTathse whaelrfe-lsifiemiolfareliinmdiunraattiioonnin{0ththelhivaelrf-oiffe18ofedlaiymsifnoarttihoenmianlteheansder2u4mdoafys14fodratyhse ffoermtahlee dmyanleamaincde1q6uidlaiybsrifuomr (tdheeffienmeadlea.s Tchoensptaanrttdoinstbriebtuwteioennlriavtieorabnetdweseenrutmheaptpweoarbotdoy.bein c`sormopupasr,tbmuetntnsot(iOnbethreg 1ef00al.ug2/0K0e2)dofsoergtrhoeuspamwphliecshianwtihede30raanngde5o0f0i0veprg/LoKssedrousmePFOS ratios over the courseofthe study. Conclusion 4Thges,e re1s0ulutgs/sKueg,geosrt3t0hautgd/oKseesinomf3alegr/tgs yainedld1e0d usge/rKuemg PinFaOdSulltefveelmsaltehtratwse,raenndo3t astnadtis1t0i0caullgy/dKigffienremnatltehsan(ocuotnt0rol14vadlauyess). iOncnrleyasdeodsesseorfum30PFuOgS/Klsevaenlsd ahbigohveerbiancfkegmraoluensd Wlgev/eKlesgiinncmoantlreosls.sigCnoinfviecarnstellyy,inocnrleyasdeodseisveorfP1F00OSg/leKve'lsaonvdehribghaecrkgirnofuenmdalleesvealnsdin30 ccolnitmrionlast.ioTnheofsaepprersouxlitsmastheolwyed14t-ha1t6PdFayOsSingimvaelneaan5d00f0emuagl/eKagt,harsesapescetirvuemlyh,alwEhliicfhe oafre afoprprmoaxliemartaesldyo2s-efdowlditgrheaanteerqhuaivnatlhentpdroesveiooufslyCrelpaobretleedd sPeFrOuSm. haTlfh-elisfeeorfumerleismuilntastiaonnd mmeotshtodosf.thNeeiwvemsertehsoudsswceoruledoifmcpormopvaerarobbluestqnueaslistoyfttohpeudbaltiashaendddlaotwaesritnhge eliqmuiitvsaolefnt dcehtaencgtieodn,evheonwewivtehsmthoerecopnrcelcuisseiodna,a.aIeaits rfeocotmhemesnedruemd tdhaattatwhoeullidvenrostalmipkleelsy bbee reanalyzed under improved extraction and analyticalmethodsnow available.
n
Som J
Lies
Advanced Research Toxicologist
i-tor
L fTTreenteeasi e iaSt t ac o 012) , frvost.
-- ngLtp1. tBu,llicona]n
Apud 2, ozno0y
References ADulnanne,r,anCd. DWi.tu(m1e9r63()197N1e).wBtlaobloedsafnordmOatlhteirlBeocdyoFmisp.a.rwFiAtihScsEo,not.onl. Bome2r0,i48c249s1. cHhaanrsaecnte,rKiza1ti,oCn lofeoarg,anLi.cAf.orEolclhoenm,icaM.ls inabnidoloJgaicsaolnm,atHi.cOs..E(n20v0i1r)o,nCmoenmtpaoluSncdisepnecceiafnicd,Tqeucnhinaotliovgye 3J5o,h7n6s6,.7J7. 0D. (1995) FinalreportanalyticalstdySingle dose dermal abcrpton/octystudy ofT6J0o4hn9soinn,Ra.bDb,itsG.i3bsMoEnnv.ir1.oamenndtOablerL,abRorEa.tor(1y9,8S0a).ntEPnhaaun,cMedN.limiationofFC.95-14C and FC-143. J1o4hCnisnornt,swJi.D,tGhicbhosloesntS,y.ra1. mainnedsOsbiemre,nt. RR.E.ik(1e9e84L)a.boCrhaotolreisetstnamci.n.-<.nhPaaunlc,eMdfNe.caleliminatioofn [c1a4Crlbpeor1n4fsionrorotcstnafetseurlafdoniaitset.atFiounofnsmmdoananiodmAmppl1ei4eCdnTloxptiecoralofguylor4,o972o.o6c.paonscsuamt. ILoahboarsaotno,ri|.es, iacn,dOSb.ePra,uR,FM.N.(1979). AbsorofpFtC-i95.o14nC in ais after singe oral dose. Riker pLeurclbokreoro,cDt.aJn,eHsasnfsoenns,iK.inJ.eCxpleerinmeennta,l rL.Ai, .BuTtoecachaolfofg.i,sL6,0,a2n3d2C,asAbes,trMa.ctT.ID:200111)0.4Background OibesrgoMn. Sajnddina,iAf.veCsasofanbdoinv,iHd.oaNloprodlgycrhel,o,rinaltaesdobni-pWheehnieya,lnsE.searnudmHeakvaensssofon&,hHy.d(r2o00x2y) Tissoe 2O.3l3.e4,yKp.enDt.acahnlodrEobbiepnhe,nKy.ntL.he(r19t8.0).Tx2i8cDlaSyipe7r0,cu1a7n1c-o82u.s sbsorpionstudywith FC-95 inalin rabbis. Riker Laboratories, Inc. St.Paul,MN.
5
Tables 1s
Table1. Biological Parameters
EE A AE 7 C Te h Tw tm --
ooke
;
w
w
w
W
C[O I= Tsp [mEJTfoEsfCu0{E 5 fN owinCO[EoEfap8lEw[E 5[iw]|
I YYEC LCNEELEEOCIL0ENCEO EECCCEE C cA ICE
ES [TsoY[C7 [5 JE owr(T s [E7C JCoEw[CsE [E5 EfCoS aETm[E wm fE w]
I I YYEECCE ECOL ECCEC LE2E0E EC CEEC E EE EE EE LEErT
.
TTF TMsepan[[778[[W5oJ[oowe[i70J[ovrf[voese[(75{5sorf[oesml[wma[[mwaa [fRAm]
[TspYiEzTEoEJoNm f0 w [om 030[E7LfoEsELwLa[wm Twa]
[[30CTIF[TMsepmf[wtojo[ooo[ouwm[wses 5orJ[ovsasr[[Tioos[[uain [[ooooo[[owaa [[wwnnT[wwaa]]
T7 sp [E 7 [E 7 JoE m(s [+N JonlEnEJEwI[ow8[EwL[LwSw]
[FR Is7 p ILsC JLvEJemLsE [7 J2 os[LnE w [i0oELwfEwSEwa
[I CTIECTsYpY[E 5 JC efC enE s [7 fTonCsL7 0oEEsEmT [EwLEa
[ECONIF soYIEsZ > TonEsLCTEwC [5owEnIE o JEemClEeo E vo fE ow]
[IW[IsMeonI[s78[1370TJwoan[imw [[30m[[wosn[s0[[55al[owirf[ssw I[=on TTowr
| BW, Tnital Body Weight
1
BW. Final Body Weight
LW: Liver Weight
1
Table2.SumSarmum PaROrSTayble
[C o5r 7] r d=ale 2T T =FeammdmeyT ]w dh] e
[ [eI [w so os mulons
LoSov A Lamoo n)
pe]
--
p [ee srd] =
:
mr wel seat ale
----
c oom]
[ wwe s soon oole ier ow oar i
Tw]
we --Co1m|1oor3]Com3 y s3w] oulBiYw]
7 [T, oem wel t3 1 ol o1n]moe m wn1} 303
{ [ 1 J[e50 1 Smosw fl sSeat[l}wow"ooilfoGwemw) ew serwi]arWemrT ] svearlieunae}
CITT-- rT 1T-- 1
NA ot Applicable.
n
Table 3. Summary Serum PFOS Table, LOG, LODZ substituted
dPoset | go. pbroots
TTieoat coby
[ [f f TIssT Toomsom(eoe s oro||__|| [[ f+ [7s fssTJooooms Joe Toomso ||
[ Cw r Joos 1 Jos t m [+ | CC --OEE T -- ETA O -- --
C 3 [+ Tw -- Is Toms--oO oo|-- | r 3 IC 7 r CE E-- [ 2} Ta IE Ts TsTo7 w oo. o[ E| -- [s Ts 1 Joom Joe ss|| [ p o [5Joir foe ams(vo [ [o F 5Tfeeassme oe s oomss[| FF [T [Two IIssToowo s ooooeo [Tg ||
[ ; rrpo Feeo m 1om> ere I - || [ [F s TsTToooowms-- Jooo s wmo|]| [F FoIE Tso TEsNfoo SO JooI s[-- 3 | [F 1own oe or1| [F Ts oo1e mA Jomoe | -- ] E [ Trahn ofaF uaTrastono(Lo010S 72m-- = 0.0275ome pmm)eor| anaehl-- 4] Trof
dbeetleocwtioons(eLOmDiZs =0.00083mpm)weresubsite fora vues atwore + SSiiggnniiffiiccaannttllyy ddiifffeerrenntt iinn ccoommppaarriissootoonn ccoonnttrrooll bbyyDSutments TTeestt((pp<<00.0055)).
is
A ------
=
Ta | | | ae
[0TF 177 "vosIw "ee 1008
05
IwTs oo
1728 170.00T7017]
[ 1 r p=r m pop e oe | [J 710.00 [53mm| 3[000 [77007]
[io|F Ta10.02 [wa T3& T7000| 0.2
TwTere
TodTool 70]
[30 TF TT1TosTamm aa T7003 1770.5 77)
[IwTa ooo Twa TaT7000J 0.0 7]
[moe TFTaT0200 Iw TeToon[T]
Tw aeons
0a T7012 708 7]
[so00 |F aTise 1 He 71728 T7699 | wan. |
Co|m | ers Tw |1TssrTa
ee Tsar
est
`T5a.Sbumlmarey Liver [PFOS] (ug/g) and Percent (%) Dose in Liver.
C T r hT mT e a mTm
Doovse || Goende
1 FFs
Ty IFFS
[vor | LIFFOS eo
[NMe11253 T[NoA T[o<QT[oNA [T<oi0QT[oNA |J<oi00T[NoA||
[NSD_T[2105[TNoA T[o<0QT[NoA T[<ot0QT[oNA |1<1t0qT[NoA||
[[SMDe_T[0000117 [[NNAA [[<0t000 [[NNAA [[<1t0000[NNAA[TNoAm [NnaA|]
FIN [MemT[o000J[oNA T[<ot00[TNoA ffsoo [35s7 [nnaam[maa ]|
[sp [2<t0q[1N2 A[TtoooT[NoA T[s003 T[6s3T[NaA TINhAa|]
[[MSeDmT[0001585 [[826757 [[<f1000QI[NNAATTOosOs T1e83 [[NNAa I[NNAa]]
I[MNemT[o000 J[NoA [051s s TIse 1Tosss 25s2 INnaAITNhAa||
[ISNoT<stogT[sNa TFoso [1350 5{oor1[522[NnaAITNnA ||
[[MSeonT[o0o1s60 [[1787 Tfooom [[8365 Tloooms [[8i6os [nNaA nTaha_||
0
[IMNesTTs036 T[3s6 T0soz T[s35 TIs0165a 3 [n Naa[N)A]
[Tsoo T[5s7 1fososif[6s7 JToswe 1{sizT[hNaA TINmA]|
[[eSDm[(0o0asr J[o8l6 T[ooims [l1es6T[oo3onTTeaos [NnAa [[Nnaa||
Tw
IsI Ts 1Is Ts T1sI Ts na TaT]S
NTs [5Sso 0os3i5 [11598[10s0s [1[5s5Nnaanana]]
|
[[SMo[m02m16[fe0 J[o13i57[[264TToomwsTTsso7 nnaaTnaa]]
5000 [ENNsE 1s I Ts 15O Ts C Te T1 s 5s |
[ISNoTTasss [13s7 Tfiseisi[51421[lsores {11s6 [17s651 1[s65 ||
[[3S5ise|155[i{sstoer [I3s5sTJiadme T(2s03TToameeI[1w7]]
COwiQonm1e0n7ta5loLbr),becan(rodvp 1.6302 00groK g ondy 4Foss(OeM
| 00 54 rhe g (op 1.3. 10,3004100Kdorson ds 4pote Gc |
|| 5000Q0u=5g.55dnogslgognrdoayss (1aSnMdEn4vpiorsotn-mdeonsteaalnLdab37).nglgandays14and 28postdose forthe 0(group6) nd | NA: Not Applisble
Table 6. SummaryofWinNoniin Noncompartmental AnalysisofMean Liver [PFOS]
To(sseara) Gander
3
uT
3
Hl
10
5v
0
?Bo
100 5000
MFFooo
NA: Not Appl8icable
Tlaawn Cararya a mean 1 00.0539 Mveaann 11 00l017 eVeaann 31 0olss dMeeamn i 002s6 HMmeeeamnn d 11 O 103194 dean ii d2l2
WELyTa)Rbda_z iRsR)t aso0w) mmah moaw om 21 wm
T(Iaas)t C(lsags/ee) 2 o502z 11 oolls 11 ooelss n1 oooanses n12o oo20le.s5 28 Goss
(AdUaCyTariuEaa) oIldess oolleess 1il:a isla; 11si03d.ie20s emer
2
Table 7. Summary Liver:Serum PFOS Concentration Ratio (1g/g2ugia).
[FaE=i1iavebr]/Esesra] PFOS Tals (ppapeal
0Dose (v3/Kg)
Gvender
ean
D1ay_post-Dose (3day)
Ww
Ww
I1Y
>2
u esan mwn
"Ww awm "3
3
r e5an WoAw
ISna nnam nwnw
u bs ean wWA
naa wI n"=
10
. sHoanowWA
w= wwmm Awn
u HsoanomWA ES
w0i.3 n1A0 nn=n w he a
'
n
. H5aan o5 s
511 50.4 uwn
100
" e
EHHooaannR)Wh
wW5hw Ib5y wiJnS
u e57an 5d2s
05.5 5as aJ
5000
N5ew 215.0
T2 s L` o w3n
u ean 13 s
20.3 05.5 9io
so" 0.8
0.4 2.5 2.4
2
Figures
Tomaamr sism Figur 1. Average Serum PFOS Vs Time.Femaleras. All doss groups Serum PFOS Vs me, lowDose PFOS.
3z m
oo ww
f0l7e
o
I
a[PDm oem eo eww
O os e D0oy_wDpesowsdat, y) sw TT OEM S000Ener
ft Figur2e Average Serum PFOS Ve Time,Ma rat. All dose roups.
Serum PFOSVstime,lowDose FOS.
sl7, Em 5 3
0100 ee os awny. 1ous doga) @
oo e--rofm on" Ze
aw --amEm en Tew
Figur3e. Average Serum PFVsOTiSme. Femalerats. 0 o 100ugdos/egrog ups. Average Ser[PuFOmS] Vs Time,010 100ugg Dose.
i ay
<0
f TM a
Eo
--a--
:J a
opi
+n
-
-- soem
5 1s E) 2 0 Aw
ay_Post_Dose (@m)
wen
Fi4g.Avuerarge Serum PFOS Vs Time,Mlerts. 01010 uggdosa groups
Average SerPuROmS] VsTime,010 100 ugg Dose.
goss 23 02i oi i. WE os
<--o0em Z=noe wsemo sm o--wwem Oy_PosDose ay)
2s
Figure Liver POS Vs Tio. Male and Fal Rat. Control dose roup. LerPFVsTSi,
gr0-
f2 os
oo foossimoeuor.w oo ssoenomos
Raibati
= ones wm
Figure 6.Liver FOS Vs Time. MaandlFomoal Rats. 3ug dose group. Lier PFS Vs Time.
oFouT
8EI on Po foo os ioenpesoaeas
www0
Zecoeerr
Zi
%
Figur7e Lier PFVsOTiS. Mol andFarmaRalse. 10K dose group. [rr--
go Zoe: T eel
Tom:
EE E T oman
. 2 en
--a
Figure 8 Live PEOS a Te. Male and Fam Rte, 0 ug dose group. Une POaTSin,
Se. gore
Jg oa FC foTrT o T
ms
hbo
rms
f o, 215. e=e
Jos
ars
F ebE en
anRtn .:
am--are,
5
f x:=: mine
ra 1 desm = ----GendersFError
.
Appendic 1: Bougcl Parameters. Indisidual snd Summary Data Tals -- gr --= t 55u=
==== I v nwoe woomswm
jo2=os aa STnn w oueasl
bJo=odm nnmoooormnonowomm
===n :5CFRR 20B 0=m
To=
5HE me
=
soto
EE
EE
= 2 no
== wBooomwo=
Tou
TT
B= a EE a wm
p=l w Tomx uw r T-=on e a5HoEamm
i E 2 2 T E Z
-
Er
22 2 I1 3=
5"EIR IE . 4 4 4
Ipe1$F: 311 Z=2 L E F f4 Y 4% 2% B ti o 2 3X -- 5w2 a 14
2
Fr 7 7y2 FT un 2 2 2 2 fr EF Ff i 24 21%
TT 5 1 317
.
Eo L. %2 41 % 7 2 3& E Frf a "424 41 21% "=TI2rFE 1si 2n3rE1 =F@33 E 32r 2314 4
.
--
EEE 2E $3 27 =z2 5 FFr 3$f 21 3a%
aT I 1 3% i :& EEF :1 2 z =0%4%
.
E E TT e Tan FZPF 442 44 03=3
F=rf 442i21=..%
gEE EI E
-_--
om 2 2 73
.
EERE TE = rr F T 44 22 7z 5 F i 2 2 52E3132Tr 3Z
.
i 2 i 2 2s= $HBEM: 44ME 42%7 "272. I23 t33 z&= E F 2 r 2 a
i $F
222:3L 3F
VT
.
F 5 r 5.) 1% $ 1 1 #7 2.4 2 4 2T % E22% E45 RZ& 5I
.
E 2[I I %3 FE 42 1tr 2 g2E 1 L1 z% f2zF 23.2%4tuo% fE2F I1FE I1II-- Z=Zz=
.
--
ERE F F r 41.42 4= 2 1% 2 5 fF 3 .4 52PE i%1 L13 F1%& E ryFP o 24 44 43 5LEFEE 44311 % 32 F2FE
,
Z 1EE iI zZ rnTm 22i 231 a8
F=$F 231 21 4Zz iET 2I%f %
>E=F 21.44iya1
IZ
FP 1 1 7
-
f 3 4%
.
ToratsIsER
Appendix 2: Individual Sera PFOS and %ofdose in sera.
TI ore SDonaey Gade RTI S5TeruagTreRS SeeaaPROS eserase
7
1Gan)
Tfm e
T Micsio ng T missing mMiscwing
3S833628
MlMiiisscssaiiinnnggg MMMiiissssssiiinnnggg MMMiiissssssiiinnnggg
33#223
iMiiststisiinnnggg
MMiissssiinngg Missing
MMiissssiinngg vissing
Ne"oabns
32i.009 0?a.057 m::issing
.
Ey
Missing Missing Wissing
ns 1130078
MMiiissststiiinnnggg
MMMiiissssssiiinnnggg
MMiissssiinngg Missing
||
E3is 60
MUMiiissassiiinnnggg MMMiiissssssiiinnnggg MMMiiissssssiiinnnggg
EEiH
MMoiisstsiinngg M0iissisinngg Koiissssiinngg
eo3abns
MW8iiststiinngg MM:iissssiinngg Mh:iissssiinngg
or u1123m33
MMViiisttsesiiinnnggg MMtiiissssssiiinnnggg MMhiiissssssiiinnnggg ||
3331%3
HiMiiatsrtsiiinnnggg MMiiiissssssiiinnnggg MMMiiissssssiiinnnggg
3533
MM9iisistiinngg MM:iissssiinngg MM9iissssiinngg |
sEoenasn
M:Miisnsiinngg
M:issing Mising
:Missing missing
wo1123005
HMMiiissntsiiinnnggg MMMiiissssssiiinnnggg MMMiiissssssiiinnnggg
37886135
MWMiilsssttiiinnnggg MMMiiissssiinnegg WMMiiisssessiiinnnggg
iEede
wM:isisieng wMoisesinng MM0isIsiEng
l5oenasn
HM:iiasstiinngg MM:iissssiinngg Mm`iissssiinngg
wor i Ths HHiittdiengn lMiisssisnigng mMiissssiinng
Fugees
T5308338
HrHisssissnihgn MMWiissEssiiEnngg MWMiissssEiinngg
3B39aH35
M0M.ii0is8ss%iinngg MMMiiicossniinnggg MMiWiissssssiiinnnggg
jo3oense
i
:o
o2
0.05 issing Missing
o
Missing Missing Missing
wo hu1i1m8s7
N0Mii0ss1asiinngg
M0i.s0sing Missing
Mwiissssiinngg | Missing
E7h8eY5
MMliiissssaeiiinnnggg MMMiiissssssiiinnnggg MMMiiissssssiiinnnggg
|
aHu 9H
HM!iilssiinngg MM!iissssiinngg MM0iissssiinngg
e5obasn
W50i.s0s0i8ng 05Mi.s0s7ing MM:iissssiinngg
i
@ or 1u1115m5%5
0o0.o00l24 G103o17 mmaiississiinnngg
vNueonnen
033.085 053 462 moSissing
5
OT Olen missing
wo u1r3e5my0
2006001:1 000.0M088 iwmiiissssssiiinnnggg
VYxoowusn
G3: ot 3d3 ais d:Sesing |
D[ ose | e Daygo Gea nde 5Animalt_(R0- s0So0r0s8.(eF0 S00e0re6aT3.pROs Mdeienssseinign
5
BH ofzaeae ee
are Missing Missing Missing
33s61o05l0
HMMiissseatiiinnnggg MMiiMisssssaiiinnnggg MMiiisssessiiinnnggg
WNoebz
H:silting M:$issing M0sissing
t5eam
MMisseslinngg MMiissainng wMiiasssiinngg
we36e608
HMHiisssitsiinnnggg MmMiiississsiiinnnggg MMbiiissssssiiinnnggg
poiet
HH8 iSnN MM0 ionng vaitsisinngg
ons
s
$
:
T5wn
MWiEsssiinngg MHiisssintg MWiisseinng
|
4 em3o01 3770088
MMiissssiinngg MMiissssiinngg
MMiissssiinngg mMiissssiinngg
MMiissssiinngg MMiissssiinngg
u3107 sobs
Moissing 5
Missing s
0Missing 5
H3aan
MMiissssiinngg WMiissssiinngg MMiissssiinngg
na3m67 365
MMiissssiinngg issing
MMMiiissssssiiinnnggg
MMMiiissssssiiinnnggg
365367776
MMiissssiinngg MM0iissssiinngg MMiissssiinngg
sbeooabrs
M3issing Missing
Msissing Missing
Msissing Missing
wor 37a0s9 30
MMiissssiinngg Missing
MMiissssiinngg Missing
MMiissssiinngg Missing
Himi1z
MMiissssiinngg
MMiissssiinngg o
MMiissssiinngg
Hsooabns 3
M5issing Missing
MMsiissssiinngg
MM5iissssiinngg
u 36367788 3630
MMiissssiinngg Missing
MMMiiissssssiiinnnggg
MMMiiissssssiiinnnggg
.
3366u 8821
MMiissssiinngg
mMiissssiinngg
MMiissssiinngg |
o
|
|Dose
Dayo
Gende
sH5eoabns Animale (3R0-
H5issing Msissing Missing | missing
M5issing Wiseing
Sera.(Pf0Sera thos idese in
Galkg Bsatse
EBt)ag/mt) Ca ena
10
1ap Fo ess
3856
00..0021 00..1009 s2.i8s9
338838535897
o0l.02 loz
o0lt08 oii
i5.1s8 826
|
Hnobs Hoan
035 .07
5< dos
5ss s.s2
so
0.002 0.013 ors |
uo 38a3810009
MMMiiissssssiiinnnggg MMMiiissssssiiinnnggg MMwiiissssssiiinnnggg
3388112
Mmiissssiingng mMiissasiinngg MMiissssiinng
"
joH0oens
MS7issing M<issing M:3issing
&
wih WED mmm
Cr Baaaam
o G 00 o om i00 EosakRs
||
W8a
gosoer aag mn :eoha
i
jNo5oebs.
GS5ooesr Sb5aoiwe os5 sasm |
wasnSiaiis
UtMiiiisntsiiennsgg dwwiiaeasiiningg hwmiiesissiignngg
iFErd
wV3iietieng 3nMinhing whiessninng
foH5oenss
tH:oisigng Mw$isasinng Missing ||
wor 3fmHe%]s
ubMiosnsgiensg wmMisIsniDng wMmisiSsiiHng
SuJaesr
vWSiEtIinNg Mi3issisinngg mw:iissssiinngg
| |
N%eoabn wo de
HM: siEng MMSiIssDinSg MM$isEsiRng Ca Ee gs
.
SSSeaeio
ooCRoooowntose RasEem
SSo3ib
M:issing Miissing i:ssing
sete Daypo Gunde Atbonywinmals (30 S0Seo0rnasn(PO Seoacesmspros b1Seashme in.
Tora Efwrei END
5pr a
eamHoiis
0vooe0ss ooommh 3Igens
aiies
$ooonr ogann :IaRn
joEoeSns
cG: aose aG: omw s: am
w a0am
HNMiiisrsIiinngg sMMiisIsniNndg wIiissNesiinRnsg
"
uSfeHa
oF ns Wm9 nEey wWg isEi
p=oebds
SW$isisinng W:WEissEinDg :issing
fr mniie
0eo0on8s ooooamdt eoIxdn||
FWuih
Go$eer oe$ ni IE3 Rn
HoooSaen
aS: oaw S:deaew Df:aEis
wo 3m366e600
iHMisnisiseng wmmiasasninnng wiissIing
afH]
i3iee Ww3 aang wE enEn
Yo%ousn
BV$iistsriinngg wMSisisigng Mnisesiing
wor wiwim
0oonp0 ooohhm aislwek |
asii]e
ao$ sn egomn 333 Bh
NHFyoevne
S:oosx :boamm :Soaim
wms35o see
difirsnessiesnvg mWJisoavinng Muriasneing | Witting wisn wiseins
soebs
w$ ie w an m8S ein
DTooserk
wDiTy po
endo AY3noimmnal _(GROEINE
SrSeaetseri.n(egPFO 5
JSesresatpenesJos TE
vM"issseeiengin |
100 FeE aone ae
|
eh
Gorm ooRm aim hnne |
soe0Hh
ooohnno odhmmn Ro8dRd
|
iHoobosn &
2:Sam $2lem ::iss Gh aE ES
uum
oor om a
is
w37o95
002 o01o7 o7m
|
w33779976
o0ll0s3 s
00:2200 5
ooslses |
Nnseoavre
s0.028 s0.208 s0.508 loos 003 ollse
` eo 3m81s6
00.12s1 o1.l3s5 s7.706
338e4470 3845
00.5220 lit
2o1l03e01s3
7136:1.6s908
Hhobs sean
35
55
$5
0438 lass 693
5
olors oso 2a
uo 331999 3800
00..0022 o0i.s1 oosl | 0.03 0.25 113
hl33080002
00..0032 00.2208 o1l2s2
s
5
3
veHsooibns
0o`.s02s6 005.02137 0Os1.2s0s3e
|
i 383308385210
000./.000112 0o.a+0t18 0o0..s4607 |
38365503 N
olool1e 5
ooro 5
o0sllsss3
.
HN5ooavne
30o.o01l5 o5aoots soo.ossmy
wo 33800 3505
0.ol019e oli
o11s1ss0
3sail7sst
33580067
oos so o15l2s2 sa5ii2e3
HyFoeSbasr
o:a 0021
5lam 02s
sdes 109
Dwoaslekg) DBoassyeFf o GendefeAniymall_(3R0- sSioerea()PFO SeTraEPOS Vsdeonse_in_
s000 1ay raw 1238
m13a:0o0 112006730 1120..122
1239
pes FIC EC
125124410
22 80.3800 115804.45s4 1ls 8.a00 |
rHooabns 5
Bs er 30
5s12i0d.e7s19 :5.6s3er
u 11221112 2121131 125 Hnooasn FE
1102.03%0 %12.06s 8se3r 11260000 1De2osl s7ilss:3 l5 ee 15 229 156.30 s1.360 s121.199 5sess 2300 aire lie
` Fue 121122344523 12 46 rHooabne 5
182001.03 20.02080 51820 5Ise dose
ausmiyn 1162803 | 1182823 o1.2i.s90 515.08 536.3 s10.413 510.47 son 6.23
wo 1ma217s8
i 12.80 1w200n3 s aal6s so ais sl
|
12171290 w
B1l0o 5
s117ss saelloas
HHaoabns
s13.000 s125.396 58.886
5
1000 eo oles
wor n12n18
5n.e23o s3a eemm
11225109 i251
00600 13020
s1m6e30z2
Ts7a4mns
rsoxebasn
5s
s5
5s
Tose aus 7s
wl E1S222
L1102i30s0 1s152c36.e2073 o81.1l907s8
112122222531
77.0425 8 0.43 sslise 2.08 sels0 70s
rHwooabns
5s
3:
ss
s.654 109.200 7.615
3
2s mds 2m
|
ar 1u2s8m3 1258
7a.1433 pe
53.095 2sl7as sos diss
1x2125386
sloezs s
5Q213 s s
5ssoods
sHo5obasn
S3 94 s31.726 5s.209 | Te olan olsw |
wo
= 1222278
20a6T0 sWiws TalIs
11222289
33l9076 3S57296 23ss
|
12w 30
ssii as l i5 es
Hobs
s
:
s
Hoan
Sar anes dao
|
so
143 15.226 1021
|: sera eros value for animal # 880-1245 was considered an outlier.
a
AS OTA Coss Sp
(NCA). Br AA Se TRE ArOR Sr
os St PROS reLow se 05
tent ErEA oEsso ti
22 -
o
2Eure i
.
ie
.=
--- NE ors
lr12 AAAvraPFOi lt Corotdsrn,
AeSor FROSTVet Low one 5
i. FREEoT, RaceUnctonsResenOnioFoanionoy)
zLoon:iloo
.
a TTT moBoe
tSon
"
Figur 13.NCAAvgSera PROS vaTime.Faert. 3 sg dos grou.
AverageSea [PFOS] Vs time. LowDcse PROS
Ran RSi EosoTec0 ece s
Te
7 oor;i
8 i
Zomaens
oa oz 4 on.reoostsesnw Tmem
Figur 1 NCA Avg Sara PROS v Tim, Mal ts 35K dosegroup.
AvSeerar[PRsOSgVs eim, LowDosePFOS
o ooSSSt BE S i ShE r corscarmoen ooo
3SgE ooo
cs
eee on Pot Oo)
"
Fire 15.4GAeAv SaSrmPEGePSFS)Tro,eF.ataLlowrDao.se8PR5OS os ru.
snASARTARSsion
ifuw ooronn;
H: E ---
== ue
FS1MGA
onFnSi Sra FOS 1TieMerts.10
sg.
Avera SrPOS] vsrn. LowOne FOS
ert oeSoErECcEEas etn
; ooo:
gz
Z
----
= = usenet
onposton
-
Figure 17. NCA Avg Sera PFOS vs Time. Famalo rat. 30 g/kg dose group. Average Sera [PFOS] Vs time. Low Dose PFOS
Rian008s RSCLsanSaaesan, 21 1207" or:
2
----
g5
-- pcroscuoss
ome -- 2 4 6s 0 1m a
Doy_Post_Doss (ean)
Figura 18. NCA Avg Sora PFOS vs Time. Male rat. 30 ug/Kg dose group. Average Sera [PFOS] Vs ime. Low Dose PFOS
tonsiE 705Donec) carn ts os ee.
000+
Z
:5
Ouvns
oo
mesons
2 4 Oay_P5ostDose5(day) wn mw wm
2
Furs 19.NCA Aug Sera FOSvaTime. Foal rts 00s dose group. AverageSea [PROS] Vs ime Low Dose PFS
ons tS i 70% SE onnGeI r T rs
0,
nom viens
ZFLoora,, o
i o oz _ ss o wm mm
2 was
Oa ostDoss (6)
igre20.NCA Avg SeraPROSvs Tim,Mal at. 00Kdoso rau
Average Sera [PROS Vs tim, Low Dosa FOS
tons iS708gEetE s aes Be
rms
10:
BZi on,on
-
ioo o-- r _4
ss
Zhe www
Oa. osDee)
5
Figure 21. NCA Avg Sera PFvsOTimSe. Female rats 5000 g/Kg dose group. Average Sera [PFOS)] Vs time. Low Dose PFOS
reves nu7g05.ecouSesEtnnA,Cr cEart s omway
100
fe -- 2c0or,
i
ovues
--
-- Pris
o 5 E Oay_PostDE ose(6ay) E)
Figure 22. NCA Avg Sera PFOS vs Time.Malerat.5000 ugg dose group.
Average Sera [PFOS] Vs time. Low Dose PFOS. rene d 705DoseN s,count srsoo
Thomas 100:
2: 0.
2
os w oy_Pow st_Dose (aday)m mw
-- prscns
5
FaiesneostuiesSteFiiecllea:ytDabelsecriwopti13v6e5Sotuattliisetrics3-W3o5-r0ktbcopoukol- (Soca low dose F0S daseripeive Sondaret
Average Sexa (6rOS] Us time. Low bose pros Touetear 3C/25H/20M08 HANONLVIeNrs`iBCoOonNreCO4V.Ne1PrAsRiBTouHniElNdT1A6Lw2a0y0N23A00L07Y33S5I1S056sRoGsant
sereings Dftouossdeb"ae:rtinoefP:lansomnantsD"saIitaGn,Eg oEbxsteeravvaatsicounlsa Ada4inistration SHL2aea5llnaagbhudatln'iaosncoginZoeanf:cohnroacdLhioass:Fbian0ssd".tL0ibc0neaesleac.rulTfairttaipoefnso:oridLaUalndiwoiirsntn wLeiisghitinpgocerpotation
Summary Tbe
Ey Cove. I fred fasA idwl LMCE Aamc,paige
0d.i0os0oe20*8 100
00.0000.53030000885 807%
2o.l0o00o.3a08t01i03s0 0.G00o5.o70180a10355
lo "lois
ool0sfsess iilideks
StNoatcee=dtvhealuceosncvaenrceraciinocnluadteddionsethteiseestviansataidodnedoffoLreesxbtdrsaspolation purposes.
Hvoo pMazaarnneiteers14c53o0u;ldLbaembexdt+aracpooulladtednottobeSaetsitmiisnatned.
Final roranecess
G8P53eEaaguscea
wsiisseing
frENeo epaarisntAs Labias pred
wvaaayy
Hnoiisssiinng Hisain
ToiiagLdanga =
aadayayy
.
a
fr0w.ea35es00dn 280000
cSiFoscateheae all
usrsaailey.l anpiarm
a2000a8558a11 5004
SA
i501
55
ANavCCerAHEERoSvEoeubpsobs EecTeintEssprea NCDeeEehRreEatsepsrec AcoOnKiTEvhIpNaEeicgbs AAAUNCTVAEEeRkpbvrreeaadpp oprbesa HIRRRTETiNasEeporbesd
anyigdtaoydrianig/seusg7 pLrrdeearyidig
anya sanmtussnkg1 aSayrsinnrytaeingsyegl dayeanyrag/al%v
aaryyd
Hiiisssasiinnngg HwHiiassiaainrn nHniiissiignn 1ii2sz1ai3inn5gg fffrrreeeeensd 2HH4ii.ss3ss7ii5nn
56
S2ot0pau5tsiBsotFsiiacldeas:'taSbolsecruigpe1i2e95Sstoavtiiisetric3s-5W5o.r0k1sopoeko]- (Sera low dose 0S descriptive Senda
Average Sera (2FOS) Ve tine. Low Dose pros aEter: 3t/i2f9/2000 WIOULVIeNrsiGNooOrnNeCO4.VN1aPzAsRiTBouWniElNdT1A6L2m0aN0g3Aa0L07Ys3S0I1S555proce
settings sHDooucsmaeble::timoefPrloasnemaisda0ait0nah,g oEbxsteeravvaatsicounlsa:r Adia nisczation HCBLaooalivsgenuhdlesaie3etnoiugoamncaf:tohmroetdlhtoads:Fhian30sd".L0icb0naeetsactralTeaetfisooenr:roiLdnaaimfwobiriatnh wLieriigahstinSgocerpotation
Sumary Table
.
TinGeay iComne C0000 a aao00
sErieed nesCigTwTl anatCag dayaemc eeign
$id5do0l0oe0 SG9i.d0ooisda0kssss 8s hie
0a.l00o2ae6s2sa3 0.0275
0G.05o.55i0030n30 actans
ond
*)
SKtoatrese-dtvhaeluceosncweenrteratiinocnludaetddaisnethteineestwiamsataidodnedoffoLramebxdtaasp.etation
NooopaMzeacrnaitnagrs14c53o0u:ldLbae nedxis2apcootualtdednoteobetnetsiteiimnayted.
Final pazasatess
cf2iqd assustea
nHiisssaitnngg
Ha Eoir3iiancssl_otwaenrbas_s inedsoiepdt
1a/ayny
Mnoiisssiinng ising
[eiragere cna
aaayyy avy
n5H.ii5ss0ea0ii5nnyd 28.0500
Ra ovceh]a
suasivaenlyd. ayaa
202801015000330 ois
purposes.
5
ACAauTUcCaHInNtEoDnoebs f jfr wre ANRCOEEIIATEESSprpersedred AcVeoiEpInpRreeedd AAASMETCIEUEE poerbesdche HrARoTinIaNgEAeoEbEs pres HRTINE ras
anyraaGsgyanrutrgiaraomgn aursaurgT
aygraagatging1 ayedP apyrard s/ntd aaanyeyandyraugy/att
aayy0 ay
sn0i.is1sa1i3in8ng iHfisrzieinnngdg smniiissstsiiinnngg pHHiisssastiinny wdiisasassinnngg 2in1.is3si3s2na0gn [
5
E Speiets see on = ue ow dn 15 cron EE
EmT os p-- es sass son iEE
Eratm nl8 EEE soyVEG ae Emm
Wme EteEms asee wwen
te Cu omen ass son on ss 0 ecporaion sees,
ici res
fr
EBREet ns
a= ife
2
wi
io
FEolly .
. wwii sssaaoi
cRVOiTgItRoEbspres fAAUcrCiaEeRSyEprepares AcRCoemIiNeeE:dobs ARNEECATNSeECtpEbrrEeaddpyoprbesa ERRETaIIsN eopbress
Spaged rail dapauitt aanydeaaryarainanal anyranyogaanylv
aay
94ep1.a9zs01t5 P5rs31t9i3e5}]1 i0o1o1336n1a0 nnii5a5an8 i1Sl1a54ze0
@
0Siot5baustBuiFscielsse:taDbelsecrwiopti1v2e05sotuattiiisetric3s-SWoorrekeboeonke]- (Sera low dose FFOS descriptive
Avera Sexa (BROS) vs tise. Low Dose pros HDaecee: 3H /25/N 2000 HINNONLVeIrNsSiKooOrnNaCO4e:U1ErAaRtTBoHurEiNldTLoAnL2a0yA0aA3o0Ln1Ys3S115S5EPho
settings BHfooisnneedle:rineo.fe"lnaosmmaatadsaitan,g cEhxsteeravvaatsicountsar Ma3tnistration LGHBaeoailsceonuhdltSaioatnnignomeenf:tohmroedc:Lhuods:bFidn5a4a".L0ic0bneaeslatcrulfTahrteoipoafnto:oridfaualnsimfviiontrthm wLieniegsh.tinTgitespolation
Sumay Table
Tindeay sSwmieme speedl nes"iUwGl aMtCa aaa me ygeigne
51000000 l8 3400 +
02.o00:000sm0e9 0.00700
0o.04o.0o00m00dm3oi0 -03l.d.3a0c30aei-mo0s05
o0o.0e02s00e06s30s00 Beatin
0`.o00g-0ir00a00e00s Codi
14.00000
10%,
*)
SHoatreee~stvhealuceosncweencteeattiaccniudaetddtonsethtaineestaismataicotnedofforLaesxbtse_sspolation
purposes
Final Paramators
SEiG Esasuenea
0g5a63me
1iSaormpaintstotwaernh_s Lambda upper
srdaopy
333 .500 33300
fesrdyia max
aedaty ay
1233.57250705080 oom
fioarcetsane Nel
sawanaredy. aria
1385..530000005s08 pid
ANASCCCTNEeEtoenahsprsons
anyoSamnraeret
5a.603o32635 ane
@
cRviEeeTeRlonperes rfEEirRaeEyReDpres ARdoowmriepgrodbs RAAuMneIe NVNEEEEpEeraanporbesa RBrRiTINtEEyopbresd
au/admyurr/ekgly aaygrgnso dagsenu, ergu/gm
aayyreaaanyyargo/gnmis aanyy0 a
sossil.i37oa3ne0sz9 a2f5s7a5e.8]5 po0I133e7l5a 2a5.l377a50e83 eSprlai
----
ESfRtoaSptuipSsatTsiielcness:t'tcabelsacriwspti1v2e45sstuattiiisesrics3Ho-r0k43bmomo5kol~ (Sera low dese b1OS descriptive Gonsaier
Average Sera (205) Ve tine. Low Dose EROS voinael: 3l/29e/2e00s8 EONLVeIrsiCNooOrnNeCO5.GN3aPrAsRtTSouUntElNaT6AuL2a0yA0iY3oA0oL7sY3S0I1S056proce
Settings Nftooicsnaeblr:tionafP:ltaosnmamteos5ui1tna5,g3 sEoxsterravvaacsicounlsa:r ads"3iniscration SHLDeeollasgaeuhrltSaki2atntigiomenef:coheroetslhtoads:bFe1i30anL.i0cbn0aeelsactrulT(ariteaipoefnso:sridLaolnntbwtiioatrrhm wLeiingcehstinTgotepolation
Sumac Table
Tidraey wComme Peelde tesTtmUaRl anMCen aan we gmeg
5si0co0on0ms08 0oo0l-0iea0cs0 3400 o.8masa0
0b.0o00.s80s86e20s40 0.0Oo0-8oE403040
se 0d
*)
SKtoatzece-d cvhealuceosnceenctorataicoinudaetd dionsethteineestwiamsataidodnedoffoLrusebxatsr_asp.olation
purposes
HooopMaazcanneicnagrs145c2o0u:ldLbaemebxdT2aiarcoolnatcdednoctobteneeisetiinmnates
Final sazamaters
PS8o53Esasustea
Hsiissssiinng
iopmrbgde iaes LLoavem:ba s athe ure;
1radayy
fnouisssiinng nisin
Tfidrg as Gn
aaayyy day
2nrii1sz0si5in0ngg 20000
Rafhrcaesedes
siiaanyld angle
10330561000880e ped
@
farvAeUsaCrtIsNES obs jrcEeEdRe:E obs NAAEUUECIAITNEREpSrpersepared fcLriEapdyred [ AAMCITNAr EE porbese t SRATIETNEVsEoRbEs pred HRT pra
aayatsadgiiandytiennnge auseaoyr/iiy1
daoytosrrsaireaogt? dayeaonLy/rteoitgsy/khnsgl daygeaaanyyragy/eatY
aPye+ ay
nH0.ia1s5i0i8n niiisssiiinnngg Hj[iorzesericnng] 0nm.ii5ss73ai5in"ng fnsiirssreaiienn]gg Hnfiirssiasi)inny hissing
ot
eFIntopisustscaFisicelean:s'tSaeblsecriaepti1v2e45stoauttihsiterics3-W3o5-r0k0bomoeke]- [Sora low dose PROS descriptive
Average Sura (PFS) Us tims. Low Dose 7e0S TDhaecre: 3C/25H/20R08 HINNONLVIeNssiNCooOrnNeCO4V.M1ePrAsRiTBouUniElNdTLA63uL0a0yA32N00A07L33Y0S1I5S56pRochast
settings HWDooidsseahle:stimofeF:lraosmmamisDsa6ci0an8,g cEhxstseravvaarsicounlsa:r Ada3inistracion CeL[alalgncrhuttloiaesntigoemnaocrmheotl:haodm:Fai3n0sdd".L0ib0SneaesaltrutTiaretaipoefnso:oridLaUalnimwfbioirahm uLeiingehaerinTghterpolation
Sumazy Table
inGeay OCoLre. smiedl maesdtise cayNtecgies cayammeeagreeen
0i3c6o0a000s D0i.o0oo5.a3ar7es8ey0n 10500 00ers
00.:09002a80e50z70s80 0.G0ou5-o1az30z90o50s
lost olsas
*)
SHtoatreie=d hvaaluceosncweenrteratiinocnludaetddoisne thteimeestwiamsataidodnedofforLaemxbtdraa:polation
purposes.
Nsoor paWzaarnneicnegrs14c53o0u:ld LbaesebxdE+arspcoolnaltdednottobeineistsiimnatnes.
Final pazasaters
Cp3os assusnes
iissianngg
YCoirngniaas:lotvuenrbaa + Earbias upper
Layayy
HSuisosinsnign ining
[Tnriagt es a
aaxyyy ay
nf5ir1ze5ii5nn0gd 14.6800
fiGrrieain ead
ssoaigaaaaly . day
13341560050066055 30857
a
ales
6
AAauCcTAEERoEbSaspsobs RcPeilErtlEaenpsres DANoCCiTEERreeFkeeparea BocUmETiIhNaEdrobs AAAOoMnECTVVEEiRpEernegdporbesd SRTTEiINnEspobrsa
doyrigrcuagy/eaotns/aags1 Pslr idg
ayaraisknsg1 ca aprneayrtaonda/nl cayranyug/nitv
adaayyy
skiiisssasiinnnggg mbniiiszaaiitnnayg jmriissasiinngg spniriezzeiitnnygg slniiiacssaeiiinngng es5i5tessesei'n
Pr]
St IEtapvusist tFiicles:saSbolrecewiopui1v3e45sctuartliisetricSs-3W5oir0k0bopoako]- (Sora lox dose #r0S descriptive Gondaecs'
Avezage Sera (7F0S) Vs time. Low dese pros oTuitneer: 3i/2i8l/s2i0o0e0 INONLVIeNraCtKooOrnNeC4Oi.M1aPzAsRiSTouHniElNaT1eA0uLa0yM3aA0oL7s3Ys0S1I0S56process
Sencings tHDoaudsmeable:rtimoefp:lansomramisvHaatiaGn,g ESxhtarsamvvaastciaoina.r Ads3inistzasion HCDLaeaollrscgbeudhaltS.aistnmigcooanftohrmoedtlh:oadn:Fbi3dn03ad".L0ib0cneaeslaterutTfarittaipoafnotr:o.ldSaUalnoiiwfioatrnhm vLeisnoehseisSgkerpolation
Somary Table
TinSear SSoneowPaed CnUested aaMMecarm nameeeign
0fD0o0om0r4 HOt
pdbo.og0dnmm0s0
so0o0uw3ss0 dsvh.emoioeaedssesse
o5C.oi0g0as0n8 ose
oC0s.o0ae0n0 had
b1o0n
lo
) *)
SHaotceke-d tvhaeluceosncvaenteatSiaocniudaetddoisne thteimeestviamsataidodnedofforLaerbxdtse_ssp.olaion
purposes.
Final sacanaters
Rcfoadr adustea
9.975558%5
rNaoigkaolrsneestLoasnh x Pred
raanyg
2S3.3052523 i'3060
fTtoHids s Sax
aapyty day
21535.16050800000 3.00
fcSiioeatehae Rea
urjaaalyl aaprig/e
19541005433502300 530
NRAoIIc NANEEERoSzvaenpeaoe
ayaaaagadilimnng 1
3af5d5e0a0 selon
&
RcveEieToRsvpered rai
aGuarydrenguy/rimidgg EE
012L5.14a79i813d80
cNwCVaaEReyEip pred Rows
usraug: aaydayragsad
3F.535e550e88 137511
;
jAA r UNTeRptreenpobs AO AEE pres
ana yeasyre azset.x
ssSilsaotnst ws
HSRrTTIaINaNEEtorbasd
aayyv a
fS&ad3e5a8n0 Sores
a ee
FfSEoaasbtaiSsatFaiitclsessaDbelsecrwiopti1v3e65Sctuattiiisetrics-0Wotrakopoako]- (sera low dose BROS descriptive Gonazion
Average Seza (6FOS) Ve tina. Low Dose pros vDaitaesl 3N/20i/20e00 HEINONLVeIcNsCiBooOrnSeCO4V.N1ePrAsRiTBouHniElNdT1A62iL0a0yA33N00A07L3Y3S0I1S055proce
settings HHDooudsmelek:o"rtamoafP:lnaosmmamisDaacian,g Eobxsteersvavtaisocnls:a Ads3iniscration SLoHeoealzlsgeohuhlteaaimsconiugmoneneft:ohmroedtl:haomd:Fai"sn3:0d".L0ibC0zeaeslacsrulTSarittaipoetnsa:roldLsUainnibwfioeirshm wLeiisgthetrinSghterpolation
Summa Table
TinGeay 0 Soe vPeeial mes"iUaSlA aaytNeCgsmt damneaginpaige
0s.i0to0sd0o08 16
0.I00G6.e35s00n90d8s5 oie
l0.o05o00s103e08s70 0".oGglo0oti10ie5zy
lonelier
2 7)
Sttoatrere=d thvealuceosncweenrceeattoicolnucaetddionsechteiseestwiamsataidodnedoffoLrasesxdtsraap.olation
purposes
Hooo paHraanmentsers145c2o0u:ld Lbae mshxEaxrapceoltastednotrobetnteisetiirmea:ted.
Final fazamaters
iCfadoa radrgusted
sHiissssiiangg
HpESoroepoSmailn]seesrstoenaandrbda_s
1aasyy
Sfgirsesien]g nizing
TiakgCane Fd
aaavyy say
Fpiisizsaninng id
aehaslsees Neal'
uwsraiaaally. aapidfet
p1i3043 0050 00336
a
oo
----
AUAIUCCCIIENNREEoEDbsspneaos c AaIERtoEnpsres uAicrieCprEeaRprea Pree AcrMiIirNEdobs AEUAAaEUMtTCEiNnNSEE:ERipEcrLrLeaEdgporbesa FSRTTIINNEE roabsd
dyrknudga/yerigs/aags Perrit
aaykarSiaavieeadd/ioeyd aaoao wetdo)sil aanyyercdaayyrragd/inat\t aaaayyv a
mmHiiisastssiiinngng iHnizisissniignn ffnrrieestni]dn s5Hi.is3sa1s4ii8ngn rHHiiisssaieiningng sHoissoitinnngg
0 --
StSTEEsNteTi,seSriicdaetrtaSbplgaerwiepci12v8e5ssutartiiLsetric3s+MSooncnkybooorke]+ (Sera Low dose pros descriptive Sondre
Average Sera [6F0S) Vs tine. Low Dose pros FDatees st3/2i0/2]006 WENIONLVIeNrsGiKooOcnNeC4O.VM1ePrAsRiBTouYniElNaTLeAvL2a0y0Aa3No0Ao5LsY3S9I1S356ekocams
settings tMDooudsseehle:rtinoefe:lnaosnoamtsDa0ai.can0,g5 oEbxsterravvastsicountso:r Adm3inistration HSLpaoealslgemsubliaamanzogiumoneneft:ohrmoedtl:haodm:bF"i5d0n3a0d".l0ibC0neaeslatcrulfTairttaipoefnzo:srisSaialnrtowtiiontrnhs LwieniegahrtinTgaterpolation
Sumnay Table
EGTMy eSreaseRre meUtIh aaActi dee ame mgage
3di.0oo00en0 h0G.ia00nd0a0 Hoo okies:
o0oi.ie0s0es0z0 o6lTINs0s0en0t
ie da
*)
SHtoatceeas tvhaeluceosncweencteratdinocnlucaets dionnsthteiseestwiansacsieondoffoLxassxstaszep.olasion
purposes.
HwoopaMraanmientgers145c3o0u:ldLbaembexdEarapcootualcdednottobetnetsiteiimraeted.
Final pacameters
RPfoqdaadsuares
Fiissstinngg
NEao mg3a oinsestLoavmesraa x preneead
saamyy
Hs:iisssitnag Hissing
Tinsasarns Ee
aGaayy ne
f8e5a0si0d:5" 30000
CRaloadcsheee all
sassjiaaayll. agian
1p5810i5090t00 L503
aE
tH
n
--------
uaCCvTeErERoEnosneope cNTieEtrEoenrp,res NAeotCCrVTEeERZpErepdrec ANFoNRCrTIhaNeYrsobs AAAUETC SNEEEpCRrrEeaDdppoenaes jHRoRTiTnEspoebesd
anyrkraagyinsaag1 Gisyiaugryrieyl
anysrgsudiasg? P Sapyr reer angrdayrogra.tv
aaaa@nyy
sHmiissstsiiinnngg sHfiirssetsiiin)gn mHsiiasstiiinnngg Ffi5rd2ie0i8nig nnHiiiszseiiinnngg sftirseyaensg
----
ES3EE2AT2sistFeiickeesntSaoblpeestwoori1v2e45sotwatthtiaetrics3-s0oerkebnorokol- (Seca Low dose F708 casceiprive Gendiron
Avecage Sera [FOS) Vs cine. Low bose Fro aTteee: 37C23H/2E00S0 WIMIONLVEeNrsCiKooOtnNaCO4V.Me1FrAsRiBTouHniElNdTJAoL0m0aN3yA0aL30Y1s0S1I5S50proce
Seceings fMoidseblesr ofPlnaosmmamisDsartiarn,g aEbxsterravvaatsicounleasr Ade"3inistration SZHLaoaelrnlcaaostiiiamsntsgiioanneaf:cohmroestl:haosm:bF"i$d0na0td".L0icb0naenlsactrulTar1t0aipoefnso:oricLaUalnimf1eohrshm Lwiesicgahy'tinHgrespotation
sumacy Tube
Tirms elSee vPeedn nesMimGeRl anMcesanagme meg
0si.0oo0ne06*8 we
oo%bi.daHi0e0d0 SN
0o6..00i6030) o`la4a3i03s1tn3e
asi Sh
*)
SMtoatrecetdhvealuceosncveenrteeatdinocnlutaetdcionnethteiseestwiamsataiaoinedoffoLrasasxecse_ssp.olation
purposes.
No paarsahmientgers145s3o0n:iaLabestesxE+rapoouttastednottobeineisitiineea:ced.
inal Farsmoters
Efgd sggussen
paisseing
FaEompaaarsisn]stloawmerba _s Pen
sardyay
imgisesasninnegg
EfToetiago
aay
sizing
aiy
134.5300000
cHiTaiarene Neat
sawraalaayl, anni
1338133111077000 az?
aga
ag
n
rABuSaCCIiEEo0bshs ReTeEeopra VNOIEENEpEre prepred SAudOmitEtereobs AAU20MeCTNVNEEERpEErEnepdporbesa fjrRoTIietsoived
aayigdesqyrnutgu/gs7 anygrSgaiysneastiaari,/nngt
sSuua1 aayneidasyouglmet aayranyrug/altv
aaayayy
Hisiessisainnnsg wsniiassaeiinngg mnfiraseaiiinnndg Ssii5sd5ti3in3ngg wfHiirzrseiinndgg 2wH1i.i0s5ss0i3nn
"" --------
faItRrtFra,i tRSaIpeeEipuiue STtatHisIticseoreksoonk ~ (5eca Low dose 10s descriptive Sencar
Average Sexa (FROS] Va time. ow ose pros Tsaitee: 3H/23E/2N00S0 INGLVeYxsSiNoOhnNeCOa1H1PcAaStTBoVunElNaTfAeStLoa5pNsaesAsesLSe.sserspor
settings BMfaiesseeble:rCinoef.P"lnaczoesnisdsatian,g oBxmtseearviaasicountsa:r asn"3intstestion DafDoegavlusesihnatadci'entmgosunaf:tohrmoedcl:haobd":Fi3i0an0:d".L0ib0CneanslatrcuHlFaiaetpieofrnoo:rtafnautsnmisitiiocchhm LwiesicgnhstinTgeerpoiation
summa Table
Tiy ne She e res Goan 6 a3000
MmUmm
eae c aan ae
mdage
mGi7eE55s moos
mpineea edm
GomwiEee udoeweenn
oGBs caaNNss eoe BBaSnP; BE
nw
7
Sottaerred tvhaeluceosncwuenrteraciinocnludaetdcionsethteinaestwias
adand
for
gE extsapolation
dew pucpeses
Final raramears
nation of Lasbans.
pNSERorsLorcEdprasleainsstusssraanma x TDaede e tr oser aiea't Suatifshntae sNuNiiEvtEw?oorbaoes
aagnyyd Gaay ariseowllaaealdy. carriSaagpaerang
33a 1558 253..050005m0 fa3r30a00t0 21C38.5560000006 pareboironness die
7s
---- ------ -- SA --
SS2fp00EAnaErens be RaRdEeEEESETT fjA SrrattaeE r n fpAi aREeTaE pres
PSeweru . arauadueg7 araPrrarangainsgt
aaa+
sroSbpa13eHm77 SfppEiiiEee Enossresteiidiidnoeernst 5fj(i 0iI8e
% es
ErSSEoISsEt,iSsotfaialctess:itaSbelmeerwiogti1v3e45sotnattiiisetrics3-Bweorrakgbookke]= (Sera ow dase pros deseripeive Senden
Average Sara (205) Ve time. Low vose bros wDhaeteel: 3N/28E/20E04 WEMIONLVEeNrsCiWooOrnNeC4OV.N1aFsAiTuoHinElNaTLAeLi2n0g0Aa3Mo0A03Ls3YS5T1S5seproce
Settings HHolioondbeel:stinoaf:plraosmnaatDsGastiaEn,g oEbxsteeravvaatsicoanlse:r Ada"5tnistration HSLSaoeomllrbgeodanatta'eim:rnoigunonanefc:ohmroedtd:haods":Fh3i0a0n0:d".L0biC0eeasslt:culTar1t6aipoafnto:retaLnUalnsibkfnioetrnhs wLeiingdehrtinSgkerpolation
sumacy Table
TinGeay sSeem sDeesm meWtTedR atMCm one ame eeg
0S:E00w0T0 8 5.EB0E5m0Y0 Mmoeors pie
mrmaeee oaCbeUisM
D VGRR r CLB0D BE Bye
hae
dod als wos dnd der Dbooww
*)
SHeoatrece=dtvhaeluceosncwaenrceeataicolnusaetsdoisnethteimeestwiamsataidodnedoffLorinenxetarsap.olation
purpases
Final Paamerers
cRfiosdxagjustes
0o.l95012340
prBNLiorreoegdBaians)cstLoammebre +
aw/ayny
003..30755062 feet]
ffiorg ye fy
daaayy Gay
2398.0900508000 10000
cRaohlialeter Soca
w"ausslaeayd ayia
i13381a55s80800 frei
RNoCcEeonoebs ananLdnegtreoe 0Sosneg .
7"
----------
aAECiomnnesnoob iAuEcCETtEuEpCrrLreEsarssepred AscOoNhmtEiacros AOAANonCCTAAAEEERpTrSeeedpporbesa HaRTTiNINEaEporbesd
Psrindg. aarKoni aetaud1 cayeionurysdoatay/i/nigtg
danyyecaayneyuagginitns.t aadayyt ay
32103151..688033304727 522o.7.3035685s8%e7 283061233.527130048746 352015150.025;;01 ifSsoeieeieissse 1315061
" ----
(uAgP/puge)nrdatii4x.o.Indiidust Livr PFOS, % dose in Liver and LiersSera PFOS amount
a Te pfeaosrne. wC e r lan Gp The RO
Tr Za S}oan E we EUSEE
oBomwo,
Coren mMmooommm
|
2wWBoooooG5GmEd Bn Ger
oSmomTmoopowm omom le fh
|
ston was mHeouOonRp
Eom o0w I0R3 owmm oomw
| i
mmeodGe8
80
moomme omoBmooowmomm
||
3mm EaEn adShoeg S08
Somwmooooompomoom ooowmm lu BG
|||
CrmmjEmoaadm
om om owmm oowm aom
|
E wmeoodoaSnnE FeooGoaRd
owoomwwm ooomm@mmooooomwwomom mow
||
m e oGo eom0pho0b oSo0pm ||
Wome ae wm
meBmeoeei aG5ER8d8 @mmwm oommoMmmm woooo@mww
---
MM FT EoddE- oowr eonEy]
woe EEHryras wowm oowmooWmB
|
wmBBBeooooEaddomSooxooooonnwmoEmoowmmoooooonmwwm
omg FE
|
wodeoodmG;R o0omn mmomw owooww
3[FmAeoos5o@omoon ormmoomm |
so
<woQ
na NA NA
|
|
wom [ON E
om om gon
om
|
vmgmoowas ooowmem, oomww oxm
|
|
ton bos FR
TToo =BB2ee3. TwR 3worwth S<Ghieonioe [su3feee vwdnAeene wEc Yee e||
Cr
gwwem osodaoynd seo
ooooommw ooa ommw moorww ol
eEJE n osGee oooB mm noLoommoLomou
HseMBe SE5 0a %,wiese pwneerwwme |
"
usT n m 3Ge
B Hen 00be
[I
owos dGRe
uwsoos 3GGRo
S Ben TEGig
wmF sn r]aaxm
isseons ;GSiRe
S Hen Efue
uF
mEameTs
oe 0
3wFTiooo$ n
5bean 35.a02
u
s7en
680
0ods
olf
ui er o:3on
s Hoan tnGos
WCioerea DEDoslfee I an
wMGrno"m Lwfeerlmse
we GaGoes
euFn E] G; ig
st aR
wo FBowCse oodn
]
BFToil
dwT o omwom
aisa dhham
mwwmoooooommwmmooomoomw
Bo wooomt mom
woom om
w wmwooooomwo mooooomw
m wo oowt moow
wom om
0ao0ii9 oz
EmERsomWwmm ie wm
GE o2f0f EDEaeER |
oes am
|
o0.n42 oolsss
asiEs owma agnii a
| |
aGH o4Er3 EfBosWwm
pLGooseter TvhMoersee oLsiivsseerrssers
wwmooommw
53/0) oomm
o mwoommnom |
wWoomm oowm
D2 13o3 aS nseees wmmw
iEe o2n% om
||
--------------
aw -- n nSi SLNn dm-- gE oomh
Crome ois ween
sae ga ns hemo ad
3B8e P86n30oo00EB8.a1s5 SfEN1.BaE08 Ehog61i.pp6e0en1o9.,8m0 ||
HEmm BOEooodh0Rs Bog
biniEyga omosaaendpe moomm in ge om
BB FR n Ndas iTE ane kol erem&
|
HormwBBaE eig0oeRn Ege
poaofnmm dmpenoape mwmow gm omaow
BB Pe n O dos M3ga eohmge eomS
HmmfmrooodoseweA phuknn pgsomg aandan
F BwaEo noeon oEfiaHme EfEEeowns idoweo
TChoo r oMmauenE GSEMEIRE MGA eREm bHE uwe vweee wjees
oemmmeooouon nnem n,pmnE FE
epnmu aeifahon oR ie
BFHAon Sa l$0 a Ge5y 3,
HaWMmWEooooooe0nmm oo
irlamnee aoogpawgmswooaowwwm
fn Goe a TggaEophgeey ow
2
es
|
Mean 0.26
1.94 35.28 7.5
TWoho MHee GEEMME m mm t nano vee suoen,
| wn
pr
--
EsFBmitoOegoSdnE
dEIeppmEdomwEe
oy ig
" =m3Wm7o98 booHmEi1.RE22 mHpi14.mme40ggoao6sa2a.an2n4 ElIo75r.pnm2n2 ||
BBn NLa Hor wBBmoOoSamEw
EfePn mhEa hbee gampeonaaew ose
Bs =BEnE ofOnbCsE
fEfSemU EhE0oE
Ebmn ha
ie Ey
NEwoodanm
wa Em
osege
owaay
BB =n eMSe tEy NBlea, hE ne tv
Eipe pRge ues khne sine ves van,
foo ALW= aoHywORSE EEmammna mo=h
PBo FgeEoeghRoe@In
Pdmmn eEeeaadEs gds
loyp bo
|
|
Homdmd mioEoE EEoedRse BF
gmmmseEuEeesaaoamzesanmor neogysne
||
|
Be da
0 5.0
mpe e ahde w be
BE RY
side 50 il
mae om
|
FmE e osm B12e46" a:dogaas
Un EE LE)
Pdeonos rNdAe
|
TRE HEEmweooRmgies
NE an I bo esems o3ea ssee
mE um 12e19 oEBn :23/e40
gm nue ia SSh32en5E.no26ged2m2e1a2s8 lx22.e76
|
|
HOT
mmmee0 me
Bd0ikm Ga
WORE
gnaImemioeos mga yieleee
ieamm oe
wT e f d:oas Sgmre eaz hapeyeeeedifisw
CEmB E e EE d Bgmm meoomm
M GmRnww H amsn
aw ge
|
BSi nTORB Ee
fsgIurEeaagbsne a
ds ea
||
Bromm EaomdGaRh me Bn
pnm i mhea onm osdanne
|
Bs Jae R:GoossmnElsioppa eohereegwd0i,
MEBI o mEna Rweee npee meeg
E yamwneeESSR :Wusme h hsor oua
gwmE ww ha
abin hs
iver 108 vale or aniout 1 6630 ms Beitelri hy odie
5
Appendi5x WinNonlin NCA Model 200 Liver PEOS,
Flor 2. NoOfAwR age Liver PFOSVaTim. Fal Rt, Codostroa,
Liver PROS Vs Time. Low Dose PFOS i Rats,
eros ns E [eErnsccna
Tan
SSf1io00lo;T a-- T --
=
0
5
A er ers
O10u.Po1t5 ocdos)20 25 30
S-- em Fre
FIO24 NGCfAvaAagLv POS Vs Ti. Ml Rat. Contd rc,
Liver PFOS Vs Timo. Low Dose PFOS in Rats,
Raae023003836Ro aa a sT pain a seec117o3n0 0 Foro; HN BETT-- Te -- = N
0 5 O10ay_po15stieo)20 2% 30 Eman
> 8 oem fro
56 --
5 trt cBO TF. 38ng, iPEOS Tr,Lowoss Prns --re on
ma
3 010;
on era " Observed
20
2
gre
4 ono6 sc8
10 12
14
FCA Aro P05Tv ttt 3drpn,
onmgZ-- E EDE A
3 1.00;
Fol
e--
2
ems
4 on [tmo8 n 10
12
Pa
= Poa
" oo
Four 27. NoO fAvaAage Lier PFOS Vs Tim, Formal Rts 10 ug dos roup
Liver PFOS Vs Time. Low Dose PFOS in Rats, ReninsRner sS s=coS eSheaknak ninescy
Zgorno! goot0o1 mer mans
OoyE _PosEto(osasyo
3oSnsteunrmts
lure 20.ofNAvCeraAge Liver FOS Ve Time. Mla Rats. 10 ugg do group.
Liver PFOS Vs Time. Low Dose PFOS in Ras, ReelsRar Saua etr,sCm drs anc ris
S100,
Zgoo, dor
E o 3) E C
o St
ASever Oay_Post0ose (day)
w es
FIRS 2 NCA ofAs Lic POS Vi Tir, Female ft. 20 ido run
Lier PFOS Vs Timo. Low Dose PFOS i Ras, or sons tBrsC Te Rearm ycnanro a
gros
foo Y or T 4
v--e ------a--
oo
9--
Prt
[rr-- On.postoin
30 ofAvs Li PFO V ir, Molt. 10 i on ru,
Liver PFOS VsTime,LowDose PFOS inRats,
nes S E Soe orv eE esttn
r 5Bo,orre. 4 sT s a ah. Lo " Observes
5 ages On.osOns in)
Fur 31.KC ofAvsrsPFOSVin. Fama ft.10d5os rga.
[A --
eats wsSSTEmSE eE e
ion
B3 oy o
o
o5 e 0
Som Observed
2
w5 ea er
4 Coro6 s8son 0
2
1"
Pr
FH32 NCAofLAersPELiUvOsTFmSOoSVLaoTwoDeu,sPsReORtSn1Rt.0d5osrKun
Rn ea72 Re aEs tEson,ee1 Broooopr
0 2 4 ooo6 nc8ieo 10 2 "w Engr
PB -----
Flour 55. NCALoifvAervePrFaOgSe LViseTriPmeO.SLoVwaDToismee,PFFoOmSailn aRtats.N5C00A02u00i dose group.
oT0 renn 0 Gcarcs am
00
[Ee
2 oo
v Cs---- wn iver Oy_Postose (day)
--rGeoncna an
Figur 34: NCAofLAivveerraPgFeOLSiVvsPTFiOmeS.VLaoTwimDeo,sMeaPlFORStsi.n5R0at0s0.ui dose grou,
es Ri Oose eson, can"esan,stsa)
gw;
Fcooo
ie oo
Css
0 ots mg, -- mew
A evscenes Ooy_PoskDosa (day)
a" ----------
SEBaeEtLreLceos'Fiieies Descriprive Stavistics Workbook - funsiciadzr)
Lives PIGS Us Tune.
Low cose 5r0S in sacs,
voiaatle: ncn 200
3H /20/N 2000
Soxtings
INGNLVIeNrsCiNooOrnNaC4OV.M1eErAsRiBToHunEtNiTLaAvL0aayA0avtoAnoLsiYSsEsSe.procaer
pfHioeosndebeol:rtiosfP:lRaosmnantadsatian,g Ecoxstsesavvaatsicountsasr adminiscrasion
DmED358di0aoAzimnsogreetf.hooprsr:aeds:dFina0dL.0ibc0neaesrstcutta1t1iioFcno:raplaumnbiMitEiocrhn IweRiAghEting
Summary Tabie
ETMeY Swray 0,00008 "3aaoo
Fihse teig53w/l3 damyreiss aayaieegeuasy o
A HeOeSl ee
GgGamEm om
ppeoomsms odemis
ZdeemNans SEES
SD02H0E6E30 SRE
sS0 5ie30me0 ome
iew
1 7)
ote the concenteacion Storced vaiuas were snei
at
dese
tine
wa
aes
NZ Ie for ancespaistion
ie purpose.
Final Pazamoters
uies in the ascinacion of Land1s.
C5f2oaEagsustea Hopines lambs 5
00.352032162
PLHaeiibbrataasnySridoewer
1vaaaaxyy
33.00801000 28.000
ataitg ase
adayayy "aly
232..1552305808007
AFcvoolecalashlae NEEobs
aapdwty red
20082156808s05 iors
ads
ionHe
"2
pAClrHEni0oobs fNaArEacEnupbreae SoeERerrheeeys
AAHmeEriiNeERoTnpasrepgons EfREiIaNE:onEe prea HRT prea
anyigras/oasrukg7 yiapryAdaiaodig aapradvaatntiiokla1 aanyraaayeuyosyi
daay3 =
aH4g.i5se0a0id0ng sifi2ss2si0ng 2pS5e0sa0t0 B17r3.e90e3% 5i3s35si0 fiSe as
B --_--
oSfpatEo!File: Sescriptive statistics Moskbook ~ (unticiedzy)
Liver POS Us Tine.
Low Dose 0805 tn rats,
fouterr ee320e20]00 Hon 200
HENIGHLVIeNrs"iNcoOanNreC4OV.Ne1BrAsRoBTuHniElNaTSAatL0aayAsat0eAtnLisYoSrTsSseroca
DDH#o0oas0mse5b1e:mrtiomoPeful:annsomnamtscsGaitanE,g0.oe0sx0etrsavvaatsicounlsasr Adm"5inistration La iambT da a. maftohSroaaLa:atm:aFian;dneheaansirtcuTt1aatnpiaofna:xtasnatvmnbs4itesotrrhsm wLeAsorheinTghaepotacion
Summary Tabie
Tianasy Sursy 0.00008 3an00
Tams nel8m31a5 dawyues/y dayeacaeyeassy
BeGSeTD. Heer
SSu oEma emma
gcpoeommlm was
moeeaSu ligne
oC0O.0i000 fu
So5 eae5m00 opm
aiek
J)
ee She concentration Stare values were
at
dose
tine
ues
added
SRE ld iw fox xsrapotcionpurposes.
Final pacamatars includes in he estimation of tamesr
fF a3 asi susted Fopints tunba:a
"o03l.0d33e90n986
aHLaEmbmErasEidpdroeerr
1/aadayyy
280.0000s8 2812500
.
Ta aiaslse
addayayy wal
i03200500280
srieecalyti]er Bhi ee
ayiwaGrayy frre
25o..l50o52s00t07e o6ias
AACTEERSEp Sos bs
wayhsatig t aig 1
boiiesiiasisnyg E08
5
--_--
jrNaveEefTonpsyroes fSurcCmcrrEEssy res MR AAMcEIrENReEEbNgyratEprnesa H[fRavEiiMseoebs
ayitipsgraindiwirkigsa adsJridalaliisg1 a- -- ngry3 aany3 a
2220.6t00000m0 PHsiiiarr0is)nsg s265o06t0503 wB<oal378 Hsfo ian
5s --_--
SoSvoeEearnts,o'Frile: Descriptive Statistics Morkbook - (Untisiedzr)
Liver PROS Vs Tine.
Low 20s 5105 te cats,
eDaetel: ach 200
3R/2I8/N20E00
Sercings
HINONLVEerNs`iKCoOonNreC4O-VH1e"PrAsRiTBoUuniElNdTLAeLSua0yM033no0z0t3yostsssessoosan
DBooasdreeb'e:rtioefP:lnaosmnasiaD1sati0an8,g cehxsterraevaacsicounlsa:r Adm4inistration
DLdDaaieoanntSaimnnugnmeaf:cohproedd:eadFimn3dh.u0bpG0eeasastrcuTtra1a5eoitofnnot:ri fatalmnbii4tioerhs vEeiTgheinegration
Summary Table
ianye uS37hs, 0,00008 5aag
We rem9e/m9 dawyuen/sdayadeegrassy 0
HTooeeoerl
oCeNAmESIoD
oosuwonnm eeSaeollnllsil
oC0.lE00fN00 NRE
Ci5m am00 Sha
raeoee
2 7
Sottaerco=dtvhaeluceosncwaanrtseatLinocniusuetsdioasethteimestviamsataisosnedoffotx aexstepo.tation
pucpases.
Final Pasaseters
faRaiqd )assustea No 55lnts_tonbaxs
00.5i938051354
LLP iandaars se over Cans
2/daaanyyy
0f3.i08s89 1416000
fC5oo fr
adaayayy wry
007.0700050038
Roicacsahe]a NCIEobs
andofwrsyy prvi
s3oa.ll0os5ee27n8yt eas
AT EOCEIeRESESpyons
ayaaaygerasg? wea
[p[ae3isHd a3
fei
9%
. NCcELiEnEaebSpsrpeeda cR2ClEEprlReaE Fees 0 AADURUNTCINIEEERoSgbrosk one REIRESTINEsSoLbsL pred HIVEpra
<aykgigraNaaaenirgg anydaiyeatgiarn3ki?sa CGaayyeeaaaayyrraasgssyyt
aayy? ar
tp3.e1ee02]6 a2381n0ss sphieoea]ni ei 50s0s 1100115353851
9 ---_--
Sores Fide: Gandazen
Descriptive
statistics
Mockbook
-
(Untitiedzr)
LieE PROS Vs Tine.
Low Gose 605 in sate,
Taetee: Hon 200
3I/2E20E0
Sereinge
HISMONVLeIrNs`iKcoOanNrCeO1VMaPxAaRlTSouYncSlNaTSAeSiL0adgAasvg0anrLssso1r5ssesmog
DNooudsmesbe:rtinoafe:lnaosnmantsosHuitnaE,g oEbxsteesrvvaastciuotnasr adm"5inistration
LC Eraimbntiaa e:remaftohproedal:raedm;feidn25adT.t0bnC0aeasalsrcuTla1r3taipostno:xiaSnaumnbii4ta5octrshn LvoRsThIeinrg ani
summary Table
TiSney sSlhs 5000083 aa
re em 99/9 caywmeia/saayaduegrugsy a
HLgeEheTrLeE emmooommeeemsr SSeeHelEuR
oS0l.B9i0E0n0 CHE
coe-hcaem0s op
rna e
{1 7)
SNToerreeed tvhaeluceasncwounstsatiinocniucaets dionsetvhineestviemsataidodnedoffoLxaasxscersnpotation
pucposes.
Final paraeaters
aoayda)dustes so gins tanbas
E08.59x500s1
Pa Fatrba:idower rats
saaaanayyg
223.10080543 1416300
ETfoaisag fe
aadsyay Br
0o1l06050%00
Ruiceriaesda'r NINE obs
aaudusSrsys aysary
13a8.0i0030t30 aa
AVAoCeSErTRnEERp,ans
ariotaagnrdiesgt orn
51[:2313]33 32.3352
iE
9%
AcNAClGCCeERoEEEnrSReaEpdrees n Ac2EeTrrEend AAOOENNCEAEETpoEresaapone RAjiTEsENobs ea RENE pred
carredrgaalsaiaiyrgsig coydaegatiiarnrifi?asi aapyaannyyruuggrsyy?
acnayy? ay
0i2a.5t000s2 22.17365808335 2s0il.e22ed8]0 si32iia 1ii3a
9
BBoTfEiEtSfHer Sescriprive Statistics workbosk - (uncieienty
LAVOE
05
VS
Time.
Low
ose
#808
in
rave,
nen
cBiantael: 200
3B/26N/20E06
MINOULVIeNrsCiKooOrnNeC4OV.M1ePrAsNiBIouEnsNiTaSAaLtoagyMiaiaonsnuistsSitssessmocann
fDHWooossLseeb:oartximooefnP:shn:aommis"aaEci0GenE,g0cB,xhcrearvarsicuetass aa2m0 intseacion
EBEaRriARanA_2,TcIacChpeescr:hoed:Fi?nd"LhuCenoseiecautTa3tE3ioLpn:La
TuOn.iItTer Santa
spanisaonn.eeinTyterpolation
TT ay Coinse. 0.000043 oan
Priesd Resi5d9s/a3l dayaruicasy dayMdnHpCeussy igs
osdooooom loS%i5EelA00iS0
0a0.6s.30s50000.5T55O00R%0
& 7
Setxaecse-d tvhaeliceosncveenrteractiiouncaeed dose
time
vas
added
ia ag or extEapolacion
purposes.
Fo pUSSATa 1930: LEaTmia coussa:noteAhebeasetsicinraascais,orLambda
SRfeadgarzjustes LYBaoaambprhlbai,sani]tisoovreaal:sses+ [fToridgies SfEhraaest fRurOcCtyHsEercbs
tarayayy ay Eoareyy aanrdilwarsy [te
HwHiaisssihtng Hiiissstsiainnng si0.so2sa6td0sd 106o.l05i55v00e05s si15s55ti88ng
0
CIE5 bs pRiEowoRparcEeebspn]rieadt fAEfiAeenEssE a AAumoUneNmcTTiAuSEcEpoEraet ns RIpASHTeIENsEEpoRneEeg rs
oraual sug dyeprigtriaoeirudnigg
anpd3a/Sgaaaelsi/tfi?syt hbaSrd-- agel
aayy? ay
aston fnnriniisesseieiinodns frsisestseinndg wHfiasreniyndg frs5i5es0tn5i5ndg frHiesesidn
0
BEAT, Sikes Gendaren
Seseriptive
statistics
orkbook
=
(nstiaazry
Lives
POS
Us
Tide.
Low
Dose
#205
in
race,
nea
Hsaeteels 200
3R/20E/20N00
Settings
HIKOULVIeNrsCiNooOnrNeC4OV.Pe1ArRsTiBVouEniNlTdLAeLu0a0yA3aw8sns0z3etissssesRooman
MpR ooudsneeb":ercT iroefP:lnaosmmaaisDs"aitIanG,g sShxseeerwesaarsicoumteass administration
aEdaattmanidt2iaongnmfeocerhthatoass:Ftined"hibGpeiesacerulFTaiettiipoafnto:eiaSnlasmtMoiEraRn vIaNiEghSeing
Sumacy Tabte
Tioney So5r 0.00008 30000
ols el5s9/e5 daywmeua/s dayeacmaeyeassy
sidloolmo oG6l:E0iR6
0G9.00e.80l020s00 o's"503300000
ine LT
7) PNrootceeedtvhaeluceosncweanrtsratiinocnludaetsdo10sethteineastxiamsataidodnedofforLaasxssieespotation pucposes.
Hioopapzleazsnaitnugcs145C3o0n:ia LbaemxbEdr2aapcaotnattdednottobetnebsitniinmea"ted.
EcifsEassured EaNoognls duae?stouwsebrda +
TiPiegsCohnegaasre iEnades ciARoealaalltais'r NINE abs
a1/wayaayy aaayayy wEr3Yy Saraaaynenuisdss
iHHiiissseaiinn Hfoirseseidn s3n1ii0ss0e0ii0nn"gg 194315030030000 3iis5:i10s05 wisn
10
----------------
jaNowCeErzozonsans fNa HcEoRnuE bi bredee SSoEmeprE ieeys A2 RAmeEreiGSeeEorenNesnnpronesa HHRRTTri opnreea
ariaesosarrinag7 anyeiaseetdaiusnrhyg aay daavteWaiitolsrist anyrraanyruesgi
aany &
fHHiirsraeiinndgg Enfiirssaeiandig isdissisin fHiiisrraisnngg spHiissyiciinngg nisianeg
0 --------
pJonEuttsFile: Sescripcive Statistics Horkbook = (uneieioqzr;
Lives
PFOS
Us
Ure.
Low
soso
BROS
in
rats,
Nh
Hoemeel: 200
3C7R20200
HINNONLVeIzNaCiKooOrnNeCO4V.Na1PxAsRiuToYtnElNaT6AiL0a0yM33Ao0L05Ys3StIaSsePROGRAN
Setesnge
HDFouodmeeble:rinoefP:lRaosrmaaisasHtGian,g Ecoxstermavvaatsicounlsasr adm"5iniscracion
HaSDenoalssneaaniititi2amnigooR.neftoherocshload:mFai5n0sdL.0ib0CneaeslaceulETairttuinoefnta:cricSaaulanbiif4aoicr0hmh eLiingehnesinPgeerpotation
summary ante
TEinYe Srse 0:06008 50a00
Tles re13m/3 dawrrei/a dayradwaegrus/s en
nsieoiomo Od03eE0n%
ooaz00nsa 2oa .0a208000
on WE
2 7
Soetaredevhaoluceosncveenrteratcihonutatedfonsethteisoescwiumsssaisocnnsofcotr aenxserdoanpotacion
purposes,
HnoopoaMzaizmneitnagrs14c5o30u;ldLbueshexai2napcaotuatdesnottotetneetsitiinmeatte.
Final razsserars
sRcaiedaEagusted No'gSints Lasts x
nniisisatinyng
ifm[aareraisniys?te1sovoembrse
1raaaaayyy
Hfiosrseindg freed
FTTeoiratg ase
aaaayy wy
ie5rz00r0 32610
ASooaeealeihee ACHe_oba
anidfrasy aay
p3p5oi5rk sod
pre
free
1
sSE wuehatoe ns Sele prea
anykarqausasnaotrrii?gs7
wwswaisaasineig
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105 --------
BLoeEtuazsyStier Descriptive Statistics orkbook - (Uneitieqzry
Laver #508 Us Tine. Low Dose #105 in race, ten 200Touetier 3H/2/2E000 WIMONVLeNrs`iKcoOonNrCeO4V1M"ePrAsRiTSouUniEtNaLTeAvL2a0yA0av0oAs0LssSo1rSesprog
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Summary Table
Tinae wGaes 000008 0.5000
Tlis Res5i9/m9 darameuass darardengeuss
Hsdooonoe 00G003G50
00f.20a060s80 sm
35i%000es0 ul
2 7
tSottaecee~dcvhaeluceosncvaensteratiinocnludaetdd1onethteioenstwinmsataisosnedoffoLx aexccosssn.otation
purposes.
roopaprMaazmnaitnegss14c53o0n;laLSaensbxdEaxrapceotuulidedmottobtenteisetiinzyated.
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RBtdaos)egustes NoL3incs usbas
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apGuiocaezse'a ACT os
anyEesudYlsyd aan
1o8:113303800780 S30
a
Hisaing
106
----------
jNauCocaneEr0 onsans deg
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So$e0a0n2rd5e1,r0eS)saier Oeseritive Statistics workbook - (Uneitiadzr)
Liver
#705
Us
Tine.
Low
Dose
0705
in
cats,
tea
Toineel: 200
33/32i8o/s2i0e0d4
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HIONLVIeNraGtWooOrnNeC4OV.N1aErAaRiuTaHinElNaTaAgLS0i0A3un0A)5LiYSsIiSaseeRocm
Nfoodmeble:s ofPlnaosmnaateb=satia]n,g oEhxsteeravvaacsicoumlsa:r Adm"5inistration
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Summary Table
inae Sish 0.00008 5.aags
me5 Re3m8/a3 cayameig/a dayadaegeugsy
wsfooemt oo03l8n8a0
o0d.d0o6a0n0 G3h5a0300
EX
2 7
Sfteatreced tvhaeiuceosncwnutsesatiinocnludaetdd1enrethiemeestvismataisotnesoftoxtaanncehoapotation
pspores.
twoopapsuaazmoaitnegss14c5o3u0:ldLSaaxbedxatsrapcoolnattdednottobtenetsitaitmiaytes,
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2vaaaayyy adaaayyy wlwryyy Eaanryyeei3adss
wisaisstasiiinnnggg siissattinngg s8n1ii3s3st0ii5nng 10801109308000068 115007:1353338650787 Hisalng
108
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10 --
SSEeSoEneSdEra,icseSnn3ier Ceseriptive Statistics Norkbook - (unciciedzr)
LAVex FFOS Ua Time. Low Dose PROS in cate, non 200ioine:l 32/238i/s20e0s0 HIMONLVIeNraCtWooOrnNeC4CV.H1ePrAsRiBTouHniElNsT6Ak0La8yA3avn0iea5us3yissasssskocas
D[ HFoousdmeeble:srr maoufPnley na:osnmaai] sastia"n,3g00Ec.0ox0sterravvaatsicountse:r Ads"3inissracion daSnecalatizirnrigoRnaftohrmoedltsahmoFainsd"LibcneaeslatcrulTa1it8aipoefnso:sridaaumlnbiicw.oiirhnn wLiesitoehreinSgcespotation
Summary Table
fiane Oslea 0.03008 bam00
MSEas Ret9/a5 cayMmCia/s day-admaegeussy weg
WEEeRTrodeGdasRp
otadEm mhoaownen
C0O2H06RR00 NYS
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fnaeew
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Final Faramaters
jf3e sagsuece. a Yo_g3lnts Lanbda.:
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1233009003008002 13900
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m ----------
SfS7ei2eerFnide Seseripeive Statistics Workbook- (uncseiectr)
LAVEE
1E0S
Vs
Time.
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505
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sats,
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Summary Table
Taianey vals ames Ses
fies e5m75 daywmeants sayaenyemusssen
m H Hico Re EDOw EOs 5Em7aEoEasehe
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sted
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ation of amano
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us --
GoSeSEnRdaoSrcseSniatoaes Seserintive Statistics workbook - (Unticiedzny
LAVST
PEGS
Vs
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Semary Table
Tianaey 5S97h5e 0.00008 oaa00
faes Rem3m9/i3 dayameug/y dayeadgaegeassy eo
fpir0ei0e]0s 2r3 .3e% 8.90 85
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53i .05070
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us r----------
Appendix 6: Statistical Analyses
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