Document 63GJm6oO2dO8jyKod5o9M3no

-hl 4' NOTE TO FILE - OPPTS 50639 DATE: October 23, 2000 FROM: Karen Lannon SUBJECT: Revised PFOS Hazard Assessment _M sia.6 03if& Attached is a revised PFOS Hazard Assessment Minor changes from the text in the original version (August 31, 2000) are found on pages 6, 7, and 26, and concern the corrected 1974 reference to Biesemeier and Harris. The conclusions were not affected by these changes. crc> o--rrren reor ---3 m <rn -- , -rZr.*pCi Fr3o CO Contain NO CBI I US00001645 HazoanrdPeArsfsluesosrmooecnttananedSuBlifoomnaotneit-oPriFnOg SData I. Executive Summary s3Ipmlene0ovar-phuen4uulmu4lmofaaptcfaicpoon5tblu4nl.bersiplcnoLiptngoeebddv.tehemfselrasopmpmilpnopmylabeelsevtoo,seoPrdphyFpabObsvameSnraakbhnlselageassenna.bmdaeIsepncnhioetimhdgoeehmftUeaeccsr.hStcie1i.ld,ad2lrr.i8eesn3ncoetuphynrepitcemesblsdel,orehwuodamdhveievsloeeeifrnniuondmhciticchgaulehetpeevgadreetilrnmoseensoerauaaflllntPaspFP,noOFdwpOSuigtlSehainntlaieeormvnael,elsanof Sampling of several wildlife species from a variety of sites across the United States has shown pwpbrleiaeedssnemusmdpaeraotebeafcldysteedodvicesicrtnaruiltrbhrsueepdtiepoctpnhiberosorufaongPfghFeeOaegxiSnlp.eotsh,sIenuwrlreiielvdcteoerbnsaitroddafsine,uatanalynreysdxepssfoo,issuPher.FdcOeEraS(ntfsdiwsouhagsmseendedaoeilutn)es.cttoleexdviecilinstytohsfemPpdFpiOebsS,rawhnaghveiechianlsthoe NStoudfuiersthsehromwetthaabtoPliFsmOSisisexwpeelclt-eadb.soErbliemdinoraatilolyn afnrodmditshteribbuotdeys ims asilnolwy ainndthoecsceurrusmviaantdhethuerilniveer. afinvde faencdesa. hSaelfruymearPsFaOnSd lseuvgeglsesitna3mreetainreedlimmailneat3iMon chhaelfm-liicfael(wt orkoefrs1,h4a2v8edbaeyesn(afpopllroowxeimd aftoerly 4 years). Based on the pharmacokinetic data obtained from a 28-day oral study in, male and tfheempalhearmmocnokkeiynse,tiac vpoalruammeetoerfsdwisterriebuntoiotend.(VJ of 0.19L/kg was reported; no sex. differences in PFOS has shown moderate acute toxicity by the oral route with a rat LD50 of 25.1 mg/kg. A onehesmtyorieaucsirrnoaLsnnCuodc5fin0seoauonlsmf-ia5rosr.n2sitaeamyltl.iagn/g1antidon dtrhaidetsnshkoaitsninbodefeurncaebrbemiptiosc,rrtoePdnF.uOcPlSeFiOwinSasawnnaeisgnafvotiiuvvnoedmintoomubsueetambgoeilnndielcyimtyiar'rrisrtotauwtdi'niegstiontfhieve Numerous repeat-dose oral toxicity' studies on PFOS have been conducted in rats and primates. Avadcvueorlsiezastiigonnsaonfdtohxeipcaittoycoebllsuelravrehdyipnerratrtospthuyd,iegsaisntrcoluindteedstiinnaclreeafsfeesctisn, hlievmeraetonlzoygmiceasl, hepatic ambgn/okrgm'daalvitiaens,dwabeiogvhet. loAsds,vceorsnevusilgsinosnos,f atonxdicdietyatho.bsTerhveesde ienffRechtesswusasmroenpkoertyedstuatddieosseinscolufd2ed anorexia, emesis, diarrhea, hypoactivity, prostration, convulsions, atrophy of the salivary glands adnodsethreanpgaencforeratsh,esmeaerkffeedctdsewcraesasreepsoirntesderbuemtwceheonle1st.e5r-o30l,0amndg/lkipgi/ddadve.plNetoiomn oinnktheeysadsurernvaivlse.d The US00001646 acbsoeny4so.5unmdmp3gt/iwkogne/e,dkeasxyci.netsAositvtrdeeoasstaemlsievanasttilaootnw,10laasmb0og.r7ke5dg/mbdragey/aktoghri/ndbgaev,y,hocynypdnoo7amcwtoiveleigtkyus's, iamnttaooxnitkare,eyahtsempeeaxnthitcibavittaedcdousoleolsiwzaasftoilooondw and hepatocellular hypertrophy, significant reductions in serum cholesterol levels, and death. Postnatal deaths and other developmental effects were reported at [ow doses in offspring in a 2- gpeunpesruartivoivnarlepinrothdeucftiirvset gtoenxeicriattyiosntuwdyasinsigrantisf.icAantttlhyedtewcorehasigedh.estAdllosfiersstogfe1n.e6raantidon3.o2ffmspgr/ikngg'd(FaIy, pups) at the highest dose died within a day after birth while close to 30% of the F1 pups in the 1.6 mg/kg/day dose group died within 4 days after birth. As a result of the pup mortality in the two top dose groups, only the two lowest dose groups, 0.1 and 0.4 mg/kg/day, were continued pinutpos)thwe esreeco0n.1d mgegn/kerga/tdiaoyn.anTdhe0.N4 OmAg/EkLg/danayd,LrOesApeEcLtivfeolryt,hbeasseecdoonnd rgeednuecrtaitoinosn ionffpsupprinbgod(yF2 rwpafeisoiignshgTt. Reversible delays concerns about the in reflex potential and physical development were also observed in this for develo`omental neurotoxicity' foliowing exposure study, to ddaawDtnee'eelcddarvroeyreesaealaeobsdlsspbeoosmiots,friesenain5pfltfitmoacehlrtaogtateeu/lifkdogfbgnehoa/c,tddatayasdtnyoswdwslaeieesgnsrkihedgeathlslaayetlbstlaooaohnwlvidgre'vehaaspiesrniogriarIrncttaeiimotofdssingceaisadndlncwemptgver/Iieeirnnlaensicysa.rotteeiabaSnrlsseieoegddrsnnevesPveineFdorla.OefotxpdSAptmeerdbvreenunennalroaotilrtanpamlaglmnatdogdeliexentvvseitcitaessailltctooyietopfornsmaxtth.liueecadniSntiltyeeiaognslmnwsisianeftouliricftedehatysehen,,vetrbiaedutyetent csoiobgusnelidrfvinceoadnt itbnererardebupbceitatisotenadsdmiinnianfeissteateclrobenodddPysFtuwOdeSyigcohuftrsaiinnmgdilgsaiergsndtaietfsiioicgnann..t iAnctrdeoasseess oinf 2d.e5lamyegd/kogs'sdiafiycaatniodnabwoevree, TrehperroedaurcetisveevteorxalicuitnycestrutadnytidesosiendththeedFaOta-mbaaslees. fFoorroenxlyamsipxlew, eseinkcseptrhioertwtoom-gaetninegraatinodndid not aifnoncrimlmuadalelseahnraeyvpereovbdaeuleucnatiteviosetnitsmoxoaitfcesidtpyebraimsseindncuoomnmblpeilmre,tiemte.odtAiplihlttyah'ro,muaganchdomkbilonoreoptdihcocldooangtcaye,,niattnriasatinuoannlcsyesoritsfaiPfnoFrhOotShweinpPoFtOenStial wvaarsiaabsisliatyyedinitnhethpehsearamnaaclyoskeisn.etMicohraenodvleirn,gthoef ePxFteOnSt oisfnpoottewnetilalluinndteerrssptoeocdiesanadndcainnntroatspbeecifeuslly awsictherttahienehdumwainthetxhpeotswuore-gdeantearaastiowneltlo.xiDciatyta' sotnudeyxpaolosnuere, pTahtehrweapyrsesfeonrtalyll epxoipsutsla'utinocnesrtiasinmtiiesssing. eSslPFoexeFonrpvrOugoemoSrshcauaclilrnlueeofvp-stnlehai-cleftgsoieoombwnoioneaefdglryPfeer,mFoxnOimetpocStoishpsmaiuounneroneiatlcshseset,eduircrotbasenaoeidlnnrdyadoywvlaoiaehnmtnrehdidtetthimermgedsurievtsdubetaidonnbtidaeettyhshoieennbmtulsteaiarhmrydmepeirhetsneeeatdilmeinpsdkdpaainlwdvdeoeiddiwdtqrhuewuleasacodsltasregu.skleotyeiDmorrsrenaeeg.tifasaloerIafodcnvnttihenaagdeidglsedaebtnibhyteldieeroasandetlaa,irnspuddntomrueiphebeuuldueltmstoavi.teoatihlonnsen.of h US00001647