Document xEDLnZVz6vZdZ56oJ2eoVBKb

381 pp AR226-097F DRAFT INITIAL ASSESSMENT REPORT PERFLUOROOCTANE SULFONIC ACID AND ITS SALTS October 2, 2000 ER =- 3a53 XR Prepared by 3m in consultation with Consultancy Jack Moore, DVM, DABT, Hollyhouse, Inc. Joseph Rodricks, PhD, DABT and Duncan Tunbull, DPhil, DABT, The Life Sciences Bill Warren-Hicks, PhD and colleagues, The Cadmus Group, Inc. [------ Contain NO CBI 000001 TABLE OF CONTENTS LU EINXTERCOUDTUICVTEISOUNMcMcARsY ws | FE IL 20 GDIESCNUESSRIAONLc INFORMAo TION ON Ev XPOSUREe vcr ore s . 30 GEeNnVerIaRlOINNTMOEFNMATIc ON 0 EXPOSUo LE w ve s n 30 EDVIrODMED(al FE EXPOSUTE convener 3.1.2 Predicted Environmental Concentrations PEC)...uwmwonemremmsmon 10 3122 32 BEfOfeRctsc on the ENVIo FONMENtr rr n e ns ns n 1 12. 321 322 EEffffeeccttss oonn ATeqruraetsitcriAanliamnadlsAqfuraotmicExBpirodssuraendtoMAaqmumeoaulssCfornocmenBtiraotaicounmsm.u.l..a.t.i.o.n.o1f2 33 rR Initial ASSesSMENt fOr the EAVIFONMEN covers ----'t 14 331 332 Risks to Aquatic Biota from Exposure Potential Risks to Terrestrial Wildlife to PFOS in Surface Waters ............ from Bioaccumulation of PFOS ......o.... 14 14 333 Other Effects. 16 4B 2 HUMAN EXPOSUIE c E or . so 321 42.2 42.3 NOoCDC-U0PCACIUOPNAAi!OENXaPlOESXUPLOESSUc TES cr oo rr som sa io nn3353 424 425 IFnOdPitrNeCctOMEIXNpGosSurTeUViGaIthEe SEN.VIcFOcNMrEiNtmcsusvrmsmrmrmrsssssssssssssssnsssnn 3388 43 43.1 MEfofdecetsofonAcHtiUoMn,ANToxHiEcoAKiRnec tics, MEtao bOISI v.v ...corve senemres nrenrnn 3388 ABIL 4.3.12 TMOOXIECOOKfINAECHHOCNSc ANA MEtADONScr res s s3389 432 43.3 ARecpuetaetTeodxiDcOiStyE STtOuXdIiCeHsY(c PHIVALE)u cm om si mn os s 4456 ABIL 4332 NP-OEASFOc SE corrmmeo mmmemmsssss ssmsmmsssst ssssmeenens eneesssmnn 4562 434 435 GREepErtoidcucTtOiXvIeCHaYndc Developmo ental TONr EY v r o em s 5594 43.6 44 ADantyaoftrhoerm HSEuUmdiaens iRnelHeUvMaAntNSInc OrMAtiono su v .e .s .6611 rr ------ i 000002 44.1 442 MBeadcikcgarloSuUnPdVaEInIdAENaCrElSyUMAeIdEiScar l SUrVeillance .s .......oumsms mmmssmsmmon 6621 443 44d WMOORTKANIYPSROUGIIEESSSc c o r ns s e 6643 45 45.1 AInDiPtiIaOlAACshse(s0sAmSeSntESfSorEDHc UMANo HEAIthc ro os ni en ne es , 6655 452 453 OHetahletrhEExfpfeerctismeonftPaFlODSataanRdelDaotseed-R0esHpeoanlstehREfeeCltsao tiono shipn s... 6706 454 445 UInnicteiratlaAiSnStEieSsSMiEnNAEssOFesRsImSeKnc t and Wo OrK in n PrOGIv ESS m er r ss e 7710 50 60 RCEOFNECRLEUNSCIEOSNSc AND Ro ECOu MMEr NDAs TIOe NS.s .. 1723 AAPPPPEENNDDIIXXIII--SSuummmmaarryyRfeoproArqtusaftoircPThoyxsiiccoallo/gCyheSmtiucdailesPr(OPPErNtiEesC.S.)......c.o.r.n.1I--11 APPENDIX APPENDIX III IV - Aquatic Exposure Data Planned-Environmental (Multi-City Studies on StUY) o.com MIL Perfluorooctane Sulfonates (PFOS).... APPENDIX V - RODUSt SUIMMAFIES crs V1 Ort ItiAscent pon PFS W 000003 (bled [ LI OFTS ABLT ES abeame Physical and Chemical Properties (See Appendix V for Robust Summaries) 32 Environmental Concentrations (PECs)of PFOS in Blood, Plasma, and 33 Environmental Concentrations (PECs) of PFOS in Liver `Samples from 3-4 Environmental Concentrations (PECs) of PFOS in Other Tissue`Samples 3-5 PFOS mm Comme Toxicity Data for Mammals: Observed Effects, Serum Levels |and Historical Findings ofSerum Organic Fluorine Levels in the General mr petrevor Serum Concentrations in Male and Female Rats after 14-weeks of 4-5 Matemal and Fetal PFOS Serum and Liver PFOS Concentrations 6 ComparisonofSerum [PFOS] after Dosing with PFOS for 42 Days Pre- `mating, During Mating, Gestation and through Lactation(approximately 13 weeks) PFOS Toxicity Data for Mammals: Key Observed Effects, Serum and Comparative Effects Among Three Perfluorooctancsulfonyl Fluoride- mre Te i Fern on | [ [11 0|OOrnall(Gggavvaaggee))PNR-EOASFDOeSvEeDleovpemleonpmeTonxnilcTitoyvSeatyiSestudies] T Sui empEs a200 4-12 Cross-foster PFOS Study Post-Natal Pup Effects. During 21 Day a4 a reEros 4-15 rC e o a mpoe mer 4-16 Retrospective Cohort Mortality Analysis for Male Employeesof the PFOS Toxicity Data for Mammals: Observed Effects, Serum and Liver NOELS from Animal Studietos be Used for Initial Assessment of Human Tr r--are . 000004 LIST OF FIGURES [=r] Hee POSF Fluorochemical Reaction Tree 3 `Cumulative Frequency Distribution of Aquatic Specics Ecotoxicity Test Results 32 Cumulative Frequency DistributionofMean PFOS Concenirations in Blood SamplesofPiscivorous Wildlife Species 33 Cumulative Frequency Distributionof Liver SamplesofPiscivorous Wildlife Mean PFOS Species Concentrations in aT `Mean Serum PFOS Concentrations for Males and Females During 182 Daysof Oral Dosing a either 0.03, 0.15 or 0.75 mg/kg/day rat Inetsc Rorm PrOS 000005 EXECUTIVE SUMMARY Introduction pPrerofdluucoerdooscytnathneetsiuclaflolnyibcyaceildecatnrdocihtsemsiacltasl (fPlFuoOrSi)naatrioenfoulrlyfrfolmuotrhienadteegdroardgaatniiocnomfooltehceurles ofrlguaonriocchmeomlieccaullep,roPduFcOtSs pisrovdeurycesdtabbyleealnecdtrreoscihsetmsifcuarlthfelruodreignraatdiaotni.onA.sSaubfsutllayntfilauloriinnfaotremdation orfelwaitdeedstporheuamdadnisatrnidbuetnivoinrionnmheunmtaanlseaxpnodstuhreesentvoiProFnOmSenhta.s PbeFeOnSdaetvevleroypeldopwrolevviedlisnhgaesvbiedeennce ihduemntainfipeodpiunlasteirounsm,ainndvtairsisouuesssapmepclieessoffrwoimldbloitfhe,ocacnudpaitnisounraflalcye awnadtenrosn-aoncdcuotphaetrioennavlilryonemxepnotsaeld mbieodlioag.icaAlnefefxetcetnssoivfethdeasteabeaxspeoshuarsesb.eeTnhdeevienlfoorpmeadtainond acvoanitlianbuleesatsoobfeJduelvye,l2o0p0e0d,otnogtehteheproswsiitbhle athneamsestehsosdmesnatnodfphruomceadnuraensdoeuntvliirnoednmienntthaelSrcirskese,niisngcoInntfaoirnmeadtiinonthDisatraepoSrett. (STIhDeS)reMpoarntufaollloofws the Organization for Volume Chemicals. Economic and Cooperative Development Investigationof High Production BPaFsOeSd fornotmheacwuirdreenvtalryiaevtayiolfabslaemipnlfeosrmhaatvieonnoptrbeseeennteadssioncitahitsedrewpiotrth,itdheentoibfisaebrlveeaddlveevresleseofffects ofnrohmuomnagnoihnegalstth,udwiielsdlwiiflel,boerutsheedenivnitrhoenmfeunttu.re tAodrdeiftiinoenathlidsaitnaiticaulrraesnstelsysmuenndte,r development TMhaeyp1r6i,m2ar0y00matnhuatfaitctwiulrlervoolfunPtFaOrSilyacnedasietsmparneucfuarscotrurmionlgecpuelrefslu(o3roMocCtoamnypla-nbyas)edanpnrooduuncctesd. oTnhe `icmopmlpeamneyntiisncgooappehraastei-noguwtiptlhatnhceaUl.liSn.gEfnovrimroosntmemnatnaulfaPcrtotuercitnigontoAcgeeansceybyantdheitesncdusotfo2m0e0r0s iannd all remaining manufacturing to cease by the end of 2002. Environmental Exposure and Effects Rceolmemaesrecsioafl PanFdOSenadnudsietsappprleiccuartsioorn,maolnedcauflteesr pcraondoucctcuursed.urAinnagltyhseeirsomafnmuafnaucftaucrte,urdiunrginwgasbtoeth swtarsetaemgseanenrdattheodseisaisnsotchieaftoedrmwiotfhscoloimdmwearsctiealwhaincdheinsdeiutshcerapipnlciicnaetriaotnesd ionrddiciastpeossethdatofmoinstof the laannddfsilulbss.eSqmuaelnlteerxapmoosuurnetstoarPeFrOeSleaasreedstiinllwtahsetesuwbajetcetrsoorftsoevaier.ralEnovni-rgoonimnegnsttaudlicfsa.te and transport Tmohneiteoxrpionsgureeffporottse.ntiAalmoufltPi-FcOiSty isntutdhye edensviigrnoendmetnotobitsabieninignfdoertmeartmiionneadbbouytatnheumdbiseprerosfion of cfulruroernotclhyemuincdaelrswaiyn .theAneontvhierronsmteundty, iunpvtoalkveesinatoglfooboadls,biaonsdphtehreiermporneisteonrcienginpsruorgfraacem waaitmeerdisat uinnvdoelrvsetsangdaitnhgertihnegpsraemspelnecseooffgrPoFuOnSdwiantmearm,msaulrfsa,cefiwsahtaern,d sbeirddism.enFtisnaalnlyd,faisnhaadndidtiboinradlspsetcuideys from the vicinity ofamanufacturing facility. presented in this report Monitoring data collected through July, 2000, are rat ni ssn ReposPFS v 000006 Nbeuemnercoonudsucatceudt,e aanndd tchherodnaitcatforxoicmittyhessteudsiteusdiiensvoplrvoivnigdefraessuhbwsattaenrtiaanldbamsairsifnoerocrhgaarnacitsemrsizhianvge pboitrednstiinalwrhiisckhs tPoFaOqSuathiacsabneiemnalfs.ounEdffheacvtes onnottbheeepnarsttiucduileadr,sbpuetciceosnosfidteerrarebslteridaaltwailodnlisfuerraongdate amvaamilmaabllei,ainntsepre-csipeesciheasveextbreaepnolgaetnieornatiesd.an Ianccseipttueatdipornsacwthiceereinsepceocilfoigcicsaplecriiessk aefsfseecstssmdeantta, awriethnot the recognition that there arc some uncertainties associated with such extrapolation. Initial Assessment of Ecological Risk `eTnhviisrionnitmieanltaaslseasnsdmweinltdlriefpeorctonacpepnltiersataiwoenlsla-raeccceopmtpeadremdetwhiotdholtooxgiyc,itwyhtehrreeisnholledvseltshaotfare derived from the various indicate that the studies. observed Under this approach levelsofPFOS from to a risk assessment, the currently wide varietyof environmental available samples data have not braeteinosaisnsdoicciaatteeda wwiitdheimdaenrtgiifniaobflesaafdevteyr,sbeuetfiftecsthsoutoldwibledlriefceoagnnidztehdetehnavtiurnocnemretnati.ntyCaelxicsutlsatinedthis aunnacleyrstias.intUysienotfhsiseerxutrmapaonldatliiovne.r dAatnauamsbaemroefaasdudrietoiofnianlteemnavlirdoonsmeenrteadlucsetsudsioemsearoefutnhederway or planned to refine this initial assessment. Human Exposures In the 1960's and 0.10 ppm. In the 1970's, 1990's, organic fluorine was identified in as a result ofimproved analytical human serum at levels less than techniques, routine measurements of sinpesceifriucmorfgraonmofhluumoarninsewcihtehmoicccaulpsabtieocnaamleafnedasniobnle-.ocTchuipsatailolnoawleedxpfoorsutrheesm.eaOcscuurpeamteinotnoaflPlyFOS epxppmosweidthflhuiogrhoecsthelmeivcealls patroadpupcrtoixoinmawtoerlkyer1s0hpapvme.meIanasulriemditseedrn um Pu FOSofm lneovne-lb osctehuae tpaatvier ornaagle 2.0 bseatmtpelrecsh,arsaecrtuemriPzeFtOhSe dliesvterlisbhutaivoenorfansgeerdubmePtwFeOeSn 0in.0n1on--0o.c1c0uppaptmi.onaRlespeoapruclahtiisonosn.going to Health Effects `mTuhletidgaetnaebraasteioinncrleupdreosdsuecvteiroanl/sduebv-eclhorpomneinctasltusdtiuedsieisn,raondeenxttsenasnidvenoarnr-ahyoumfagnenportiomxaitceis,ty fests, teoxxpiocsoekdinweotirckewrosrakreanadvacihlarbolnei.c Tsthudeicsst.udiIensaadrdeiotfigono,osdeveqruaallietpyiadnemdiaoclcoegpitcaablleinfvoerstuisgeatiinonhsazianrd evaluation. SmoervtearlailtyinovresstpiegcaitfiiocncsliinnivcoallvsiinggnsflautotrroibcuhteambilceatlopPrFodOuScteixopnoswuorrek.er3sMshhoaws ncoonedvuicdteendcemoefdiecxacless tseusrtvseiilnlcalnucdeoinfgpleirpfildsu,orhoecmhaetmoilcoaglicparlodpaurcatmieotnewros,rkeenrzsyfmoersovaenrd 2101 ydeiafrfse.renAt bhaotrtmeroynoefacslsianyicsa)l suphotwoe6dpnpom.assAocmioarttiaolniwtiytshtPudFyOsSholewveedls;notheexsceesfsinmdoirntgaslwietyrefobraasneyd coanusseeorfumdelaetvhe,lsiinnclwuodriknegrs cancer. Allof this information suggests that workers are not at risk at the serum levels reported. Dra nitsessment ReportPFS " 000007 SItiinceretahseonparboldeucttoiaosnswuomrekftohrecsee swtourdkieerdsihsalvaergtehley hmiaglhee,stthleesveelstoufdiheusmdaonneoxtpaodseuqrueatteolPyFrOeSp,resent women. It is noted studies with respect t(h0atthmealnaetaurnedoffaedmvaleersmeonefkfeeyctss responded observed. similarly in sub-chronic dosing tRheesuplrtismafrryomtasregveetraolrgraenp.eaMtadnoisfeesttoaxtiicoonlsoogifclailvesrtutdiisessuecornessipsotnesnteltyodheimgohnsdtorsaetseotfhaPtFtOhSe liinvcelruidse reendluacrtgieomnenintsoefrtuhme clhiovelresatnedroalpparaereenatrlayltreersaptoinonssesintomePtFaObSol.icThpreosceesesfefse.ctsLoivcecrurenilnarragtsemaesnwteallndas monkeys. rAelssuoltoatfhmiagthedronsaelsePxpFoOsSuraedvdeurrsienlgyfaeftaflecdtesvseulrovpivmaelnotfrRaetdpuucpesdiwnetihgehtnegoaniant,aalbpoerrtiioodnosfanldife as a orensodrepvteiloonpsmaernetsaelemnilinesdteovneelso,pimnecnltuadlinsgtupdoisets-naattatlhenehuirgohleorgdicoaslesdetevseteldo.pmTehnetr,eorweornefnerotielfiftyecatnsd estrous cycling in offspring in multi-generation studies. pMruelsteinptlea gheanzoatrodxifcriotmy ianstsearyasctcioovnewriitnhg gaevnaertiiectymoatfeernidalp.oiTnhtes rdeesmuolntsstorafatetwtoha-tyePaFrOcSandcoeerssntoutdy in rats will be available in the next several months PFOS is well-absorbed elimination half-life for orally PFOS and very slowly eliminated is approximately 300 days from the body. The in humans, based on mean serum a continuing study sotfurdeiteidr,edalftlhuoourgohchiet mciacnalbewofrokremres.d mPetFaOboSliiscanloltymfertoambooltihzeerdfilnuoarnoychoefmtihcealmsulctoinptlaeisnpiencgitehse dpoeerfslunootroporcetfaenreesnutilaflolnyyldimsotiriebtuyt.e tUonlfaitktey tmiassnuye,cphreemfiecrarlisngoifensntveiardotnomeasnstoacliactoenwsietqhuepnrcoete,inPsFiOnS blood milk. and Due liver. to the It has good been found to cross the placenta, oral absorption, poor elimination and and there is evidencefordistribution extensive protein binding, PFOS in PcoFnOceSntcroantcieonntsraitniolinvsercaanndbeseursuemd aarseapnroipnotretgiroatneadl mteoacsuumrueloafteixvepoesxpuorseuroev.erTthiemree,forreeg,arsdelresusmof source. mSeevcehraanlisinmv(ess)titghartoioungsh hwahviechbePeFnOcSonedxuecrttesdiotsrtaorxeiciitnyp.roWghrielses tnootbectoemprluentdeelrystuannddertshteood at this atsismoec,itahteedmewcithhanfaitsmme(tsa)booflitsomx.icity is thought to include changes in metabolic processes Initial Assessment of Human Risk rReevteraolsepdecetxicveescsomhoorrttalmiotrytailnitaynyascsaetsesgmoernytosf doifseflausoer.ocPheFmOiScallepverlosduucptitoon6wpoprkmerins phraovdeucntoiton lwioprikdse,rshehmaavteolnoogtibcepeanraamsesotceirasteadndwi1t1h daibfnfoerrmenatlihtoiresmoinn eclvianliuceasl)t.esCtoinngsi(dcehremiinsgttrhieesstiundcyluded pirnfoodrumcaetitooxnicaivtayil(acbhloeletsotdeartoel,laonwdergiinvgeanntdhelidviesrtianbcntolrymhailgithieersP),FiOtSisluenvleilkseilny atnhaitmawlosrkneercseswsoauryldto have these abnormalitiesa the levels to which they have been exposed. Current knowledge rat ilvest Report POS wi 000008 tihndaincpatreosdutchtatiognenweorrakleprospuatlatthieohnisgehrearleenvdeolsfatrheearpapnrgoexiimnattheelsye tstwuodioersd.ersofmagnitude lower Aeflftehctosugahretchoenrseisitsensto.meFuspretchieersmovraer,iatthieonfaicnttthheatletvheelssaatmwehmiecahsuPrFeOoSfeixnpdoucseusreto(xisceirtuym, tvhaeluteoxsicf.or aPnFdOSul)tiimsautseeldy htouemxatnrarpioslka.teThaceroisnsfosrpmeactiieosnraevdauicleasbltehetoundcaetretoainnttoyxiinciutnydaesrssotcainadtiendgweixtphoPsFuOreS. osredreurmsolfevmealgsniintdiucdaetelsotwheart PthFaOnSselreuvmelsleivneltsheingeanneirmaallpsotpuudliaetsitohnataraereapapsrsoocxiiamtaetdelwyitthwnootoadtvherresee health effects. Conclusion `sTuhbisstarnetpioarltbsoudmymoafrdiaztesa trheelaitninfgorhmuatmiaonn atnhadteinsvaivraoinlambelnetaalsoefxpJousluyr2e0s,t2o00P0F.OSThaenrdetihseapossible bfiooulnodgiicnalocecfufpeacttsioofnatlhaensed enxopno-soucrceusp.atTihoinsalinpfooprumlaattiioonnssuagrgeensotts atshsaotchiautmeadnwistehruamdvPerFsOeSeflfeecvtesl.s Similarly, Additional levels found in the environment research now underway will be and in wildlife are used to refine this not associated with initial assessment. adverse effects rat itlAsesonesReportPOS 000009 INTRODUCTION Background The human health and ecological risk assessment process for PFOS contained in thirseport follows the methods and procedures outlined in the Screening Information Data Set (SIDS) Manual ofthe Organization for Economic Cooperation and Development (OECD) Programme On the Co-Operative Investigation of High Production Volume Chemicals (OECD, 1997). In particular, this report follows Assessment Report, which is the provisional guidance discussed in Chapte4rof for the the outlineofthe SIDS Initial manual. The environmental portion of the SIDS Initial Assessment Report is effectively a Tier I Screening-Level Risk Assessment as envisioned by U.S. EPA. This format was followed recognizing that this initial assessment report is to be part of the OECD Existing Chemicals Program. Overall, the assessment presents, evaluates, explains, and combines information on PFOS exposure and effects into an initial assessmentofpotential risk Based on current information, the observed levels of PFOS from a wide variety of samples are not associated with identifiable adverse effects in humans, wildlife, or the environment. The information in this report is based on a substantial bodyofdata and represents our current knowledge. Additional information is currently under development and will aid in improving this initial assessmentofrisk of PFOS to `human health and the environment. dSeescctriiobnes1oiftsthpihsysriecpoocrhtepmriocvaildepsrotpheertPieFsO;SanCdAdSisncuumssbeesr,thmeobleehcauvliaorrfiomrpmluilcaa,tiaonnd`socofmtphoessietion; characteristics, such as anticipated sources, sinks, and bioaccumulation. Section2 presents general information on ecological and human exposures to PFOS, including its uses and function, production volume and expected exposure pathways. Ecological exposure, effects on aquatic and terrestrial ecosystems, and other ecological effects are described in Section 3. Human health exposures, potential hazards, and risks are evaluated in Section 4. Section 5 presents the conclusions and recommendationsof this assessment, and the literature and data `sources upon compound's which this documentisbased are listed physicochemical properties are included in in Section Append 6. ix Su I. mmary Reports for the Appendix II presents `Summary Reports for aquatic toxicological studies. Reports summarizing the environmental exposure studies are included in Appendix III. Appendix IV lists planned environmental studies on PFOS. Appendix V contains summary reportsof mammalian toxicology studies. Overview of PFOS `The fluorochemicals discussed in this document are produced by an electrochemical process that exchanges allof the hydrogen atoms ofan organic feedstock with fluorine atoms from hydrogen fluoride. The highest volume perfluorochemical produced in this way is.perfluorooctane sulfonyl fluoride 2000. Using this (pPeOrSflFu)o.roOorvgearniecigmhotlmeiclullieonaspoabuansdiscofbutihlisdi`ncgobmlpoocukn,dunwiilqluebechpermoidsutcreidesicnan be created by further reactions with functionalized hydrocarbon molecules. These `compounds repel wthaetierrparonpderotili,esreudnudceerseuxrtfraceemetecnosnidoint,iocnast.alyDzeepoelnidgionmgeruipzaotniotnheasnpdecpiofliycmfeurnicztaitoinoanl,daenridvamtaiiznattaiionn i 000010 PorFOtSh.e dePgFreOeSofispotlheymsetraiblzeatainodn,pesruscishtePnOtSeFn-db-apsreodducctomthpaotuhnadsstmheapyotdeengtriaaldetoorbimoeatcacbuomluilzaetet.o In the under environment, any observed PFOS is resistant conditions except to chemical and for combustion. biological PFOS or changes and does not precursors enter the degrade tehnevmisreolnvemse.nt Mtehrcohuagnhisfamcstobryy wdihsicchharPgeFsO,Sascamnanbuefatcrtaunsrpionrgterdestihdruoalusghinthperoednuvcitrsoonrmeanstpriondculcutdse transport in and uptake surface water, adsorption onto particles present by aquatic, avian or terrestrial organisms. in air, surface water and sediments, `The ability to detect and quantify PFOS and environment has been limited until recently, its precursor compounds at when reliable and sensitive very low methods levels in the for extracting, asveapialraabtlien.g,Faonrdthiidsenrteiafsyoinn,g kannodwqlueadngteifoyfintghetehnevmirinontmiessnuteaslafnadteoenfvtihriosnmcelanstsaolfscahmepmliecsablsechaamse pbaeretniteinohnainncgebde.havRieosre,aarcnhd issigunnidfiecrawnatysutrofaascseeascstiPviFtyO.S Uanccceurmtualianttiieosnaibnotuhtetehnevaiprpolnimceanbitl,itaytyopfical cexoimsptliincgatfaetteh-eancdh-atrraacntseproirztatmioodneolfs tahnedegnaviprsoinnmpehnytsailcfoactheeomficPaFlOSan.d Meonvrieroinnmfeonrtmaatlidoantias ablesiong rgealtehaesreesdftroobmetptreorduuncdtemrasntuafnadcetnuvrieroannmdenustea,lifnactel.udTihngisdeivneclluodpeisngefffoarttes-atnod-hterlapnscphoarrtacmtoedriezles and designing methods to sample various habitats and speciesof interest, lPoFcaOtSionhsa.s bItei enpfeorsuinsdteanttlaonwdlweivdelesspirnesaadmpinlehsuomfahnupmoapunlasteironusm. frTohmesmeevecrhaalnsiosumrsceasnadnpdathways feading to its presence multiple sourcesof the in human blood are compound. Some not may well characterized, but iti arise from environmental likely there are exposure to PFOS or precursor molecules, or from production workers have the residual levelsofprecursors to PFOS highest known blood levels of PFOS. in commercial products. 3M Epidemiological and medical `seuxrpvoesiulrlea.ncAensetxutdenisoifvethteosxiecwoolorgkiecrasl hdaavteabnaosteaosnsoPcFiaOtSedaanddvesrpesceifhiecalptrhecefufrescotrsmwoiltehctuhliess cionnftoirnmuaetsiotnoibnedidceavteelsotpheadt.cuWrhreinltelmevueclhsowfoPrFkOiSn tahries anroetaaisssotciilatiendpwriotghreisdse,nttihfeiaabvlaeilaadbvleerse effects to human health. `tThheemaonsatlyatciccaulravtaeluiensforremparteisoenntaevdaiilnabthliesarseopforJtulrye,su2lt00f0r.omFovrarthiiosusdamteat,hfoidnaolloregpioerstsanhdavreepbreeesnent pirsessueendtolry abreeinign cproenpdaurcattieodn.toTcoomepnlseutreeltyhechmaorsacttearciczuerastaemapnlaelsytuiscaeld riensutletsstipnogsasinbdlea,nawloyrsiksiosver wthheiclahstthfieswdoyecaurms.enBtasisedbaosnedthweilrlesbueltrseovifsefdu.rtThehrerpeufroirtey,antahleysniusm,btehresvianlutehissidnotchuemreenpotrtwsouulpdon also be modified in future revisions. Drath nitsesResportPROS 2 000011 1.0 IDENTITY Chemical Name: Perfluorooctane Sulfonic Acid CAS Number: Various, including: 1763-23-1 (acid) 29081-56-9 (ammonium salt) 70225-14-8 (DEA salt) 22709455-73-97-23-5(p(olittahsisuimumsaslat)lt) The and perfluorooctane sulfonate anion (PFOS) has no specific salts are all considered perfluorooctane sulfonates. CAS number. The above-listed acid Molecular formula: ~ C,HF,,0,8 Structural formula: CR CF CF CF NCon CF, ch, Ch Ch o Synonyms: 1-Octanesulfonic acid, 1,1,2,2,3,3,4.4,5.5,6,6,7,7,8,8,8- heptadecafluoro-; 1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8,8Heptadecafluoro-1-octanesulfonic acid; 1-Octanesulfonic aHceipdt,adheecpatafdleucoarfol-u1o-rooc-t;an1e-sPuelrffolnuiocroaoccitda;nPeesrufllfuoonrioc-nac-id; octanesulfonic acid; Perfluorooctanesulfonic acid; Perfluorooctylsulfonic acid Table 1-1. Physical and Chemical Properties (See Appendix I for Robust Summaries) Vapor Pressure. n-Octanol/Water Partition Coefficient Air-Water Partition Coefficient Solubility in Pure Water Dr i AssenRorFOS 5/05/99 2/11/00 3/19/00 5/03/99 331x10P@20 C Not measurable 0(<2x10%) 519 mg/L ; 000012 1.1 Discussion PFOS appears to be undergo hydrolysis stable in the or photolysis. environment. Based on an This compound is not biodegradable and analysisof bond strength the compound does is not destroyed by combustion at high temperatures. The very low vapor pressure and immeasurable air/water coefficient indicate that volatilityof the `compound is insignificant. PFOS hasa seawater to solubility of about 519 mg/L in pure water. about 25 mg/L. These data suggest that any Solubility decreases PFOS discharged to significantly in a water source would tend to remain in that medium, unless it is adsorbed onto particulate matter or assimilated by organisms. If PFOS does bind to particulate matter the material would ultimately end up in vthaerisoeudsimleocnatt.ioFnusratnhedrtshteubdiynidsiungndpeotrewnatyiatloo fdePtFerOmSinteotsheedipmreenstesn.ce of PFOS in sediments from PFOS is not anticipated to be present in the atmosphere becauseof ts extremely low volatility. In fact, obtaining an air/water partition coefficient reading for PFOS has not been possible `PbFecOaSusies tchoenpsairdteirteidonuinnlgikhealys.been too small to measure. Therefore, atmospheric dispersion of nB-eoccatuasneool/fwattheercpoamrptiotuinodni'nsg scuoreffaficceiaecnttihvaesprnooptebrteieens paonsdsitblhee.teTsht eprdoitfofcioculltityseilnf,mdeeatseurrmiinnginthgisthe coefficient is caused by the formation ofa third layer between the water and the n-octanol. Because the octanol/water and transport mechanisms, coefficient a different is te used extensively st method will be in models to predict bioconcentration used to determine the coefficient. An actual bioconcentration study will also be performed. Even with this information, classic models (which are based on log P, or K,,,forpredicting bioconcentration) may not be appropriate. Studies performed on laboratory rats show PFOS does not bioconcentrate in the lipid fraction but tends to bind to certain proteins. These findings may `negate the utility ofthe conventional models, whichare based on measuresofaffinity for lipids. ornmi 000013 : 2.0 GENERAL INFORMATION ON EXPOSURE General Information on Exposure Peleercftlruoocrhoeomcitcaanle fsluulofroinniactiaocni.d T(hPeFOsSt)artisinag ffueleldysftloucokrifnoarttehdeoerlgeacntircoacchiedmipcraoldfulcueodribnyation reaction fislu1o-roicdtea(nPeOsSuFl)f.onyPlOfSluForiisdae caonmdmtehreciparliimzaerdy pprroodduucctt ptorosdoumceedexitsenpte,rfbluutoirtooisctparniemasruillfyonaynl PimFpOorStaisntitisnetleafrmceodmimaeterciinatlhiezseydnpthreosdiusctofprhoigdhuecredmoflreocmultahre wheiygdhtrfoluolorfyocPshOeSimFis.cal3pMrosdeulcltss. sauprpfraocxtianmtataeplpyli5c0a,ti0o0n0sp(omuanidnslypefrirye-fiegohtfiaPngFrOfoSamisn avanrdiocuosatsianltg afodrdmist.iveIst)i.sUunsieqduefocrhaemviasrtireiteysofare hcryedartoecdabrbyofnurrtehaecrtidoenrsi.vaPtiOziSng iPsOrSeaFcttehdrwoiutghh tmheethsyulloforneytlhfylluoarmiidenemotioeptryoduusicnegecitohnevrenNt-imoentahlyl aomriNd-eest,hyolxapzeorlfilduionroonoecst,ansielsanuelsf,oncaamribdoex.ylaAttesthainsdstaalgkeo,xytlhaesteesianstecrommemdieartceisaclapnrbodeuuctsse.d tTohmesaeke einttheyrlmpeedrifaltueosrocoacntabneessuulbfsoenqaumeindteltyharneoalc.tedThweisthe eitnhtyelremneedicaatrebsocnaantebteoufsoerdmtocimthaekreN-admieptahteysl,or N- `phosphate products. esters, fatty acid See Figure 2.1. esters, urethanes copolymers, and acrylates as commercialized [ET r------ s 000014 Figure 2.1 POSF Fluorochemical Reaction Tree Alcohols Fatty Acid Esters Urethanes PhosphaleEsters Copolymers Adipates Acres N-Alkylperfluorooctanesulfonamidoethanol Amides Oxazoldinones Amines N-Alkyiperfluorooctanesulfonamide Silanes Carboxylates Alkoxylates Quaternary Ammonium Salts Amphoterics Peruorooctanesulonyl uoride Sulfonates y---- . 000015 Tprhoecessesceosndthaartydroeancottionnescepsrsoadruilcyinpgroaldluofcethpeusreepdreordiuvcattsi.vesThaereresimnaglyeboer vseaqruyeinntgiaalmobautncths of arfleucoarrorciheedmifcoarlwarredsitdouatlhse(fuinnraleapcrtoedducotr.paTrytpiailclayllrye,acttheedsestraerstiidnugamlastaerreiaclusrroerntilnyteprrmeesdeinatteast)athat ctoontcheentsrualftoinoynlofflu1o%riodre glersosuipnocfotmhmeesrecireasliidzueadlsprcoadnucbte. reTmhoevneodn-tfhlruoourgohcahevmairciaeltyomofideetgireasdaadtdieodn psruocchedsesgersa(dcahteimoincawli,llebneviPrFonOmSe.ntHali,ghaenrdmmoelteacboulliacr).weiTghhet tpeorlmyimnearlifclfulouroorcohcehmeimciaclamlopireotdyucotfs tend to be stable and do not degrade to PFOS by these same processes. `fTloutoalrowcohrelmdicwaildse(PpOolSyFmeprrsodauncdtimoonnboyme3rMs)inar2e0f0o0rmwiulllatbeed8w,i0t0h0,w0a0t0erIbos.r sPolOvSeFn-t,dewriitvhetdhe ffolrumourloacthieomni.caTlotcaolmpfolunoernotch(eomrifclaulosroolcihdesmiicnacllusdoelitdhse)hryedprroecseanrtbionngraeavcatrainatbslecopemrbciennetdofwitthhe the fflluuoorroocchheemmiiccaall sstoalritdisnrgemparteesreinatltahnedmadjoorniottyroefprtehseenttottalheprPoOdSucFtimoonloefcusluelfiotsneyllf.ba3sMedproduced fluorochemicals in the world product categories include: The breakdownof3M fluorochemical production into different Surface Treatments (High Molecular Weight (MW) polymers or formulated products solids) with low percentages of non-polymeric FC Carpet Protector Fabric/Upholstery Protector Apparel and Leather Protector Protective Products for After Markets and Consumer Application Paper and Packaging Food Packaging Protectors (Phosphate esters or high MW polymers) Paper Products FPierrefEoxrtmianngucieshCihnegmFicoaalmsC(oLncoewntMraWteschemical substances) Mining and Oil Surfactants Electroplating and Etching Bath Surfactants Household Additives Chemical Intermediates Coatings and Coating Additives Carpet Spot Cleaners Insecticides Raw Materials Pmoatneunftaicaltusroiunrgceospeorfahtiuomnasnanodr ewnavsitreosntmreenatmasl, etxhepomsaunruefatcotPuFriOnSg ionpcelruadteiotnhseapnrdodwuacsetre'sstreams of users of POSF-based commercial products fluorochemical products, and the use or degradationofsome containing POSF-based fluorochemicals. final Dra itl sessReportPOS ' 000016 `(T3hMe)prhiamsaarnynmoaunnucfeadcttuhraterisofprPoFdOuSc-tbioansoefd tchheesmeicmaatlesricaalpsabwlielolfbpeotseunbtsitaanltliyaldleygrdaisdcionngttionuPeFdObSy tuhseesenwidlolf c2o0n0t0i.nueMafonrufaalcitmuirteedatnidmedipsetrriiboudtitohneroefafatefr.ew,Thweelcl-odmepfainneyd ipsrwoodrucktisnghawviitnhgtehseseUn.St.ial EPA and with its perfluorooctanyl customers to implement chemical products by the an orderly transition end of 2002. away from all such raf ia sessment epon Pr0S . 000017 3.0 ENVIRONMENT 3.1 Environmental Exposure Tinhitsheseecntviiornondmiesnctu.sseAssavpaairltaoblfea ilnafrogremrasttiuodny,onmotnhietporreisnegndcaeotafhpaevreflbueoernooccotlalnecetseudlffoornastuerf(aPcFeOS) ``wmaotneirtocroilnugmpnrosagmrpalmesh.asSruesmumltaerdyinreapnoarltyssiasroefpmreosreenttehdainn4A0p0pearncdhiixveIdIL.seArugmloabnadl bliivoesrphere specimens Section 3.1 from and a wide rangeof are summarized aquatic and terrestrial in Tables 3-2, 3-3 and species. 3-4. These data are described in 3.1.1 General Discussion Exposure Potential OmanteerpioatlesntiinatlhseowuarscteoefstPrFeaOmSs geexnpeorsautreedifsrtohme rtehleemasaenutfoatchteuerinnvgirpornomceesnst,ofsuPpOpSlyF-cdhearinived dopeetreartmiionnast,ioannsd, cesotnismuamteesroufsc3.MBawsaesdteonsterxetaemnsgievneereantgiionneehraivneg bcealecnuldaetriiovnesd.an3dMmahsass bnaolance information on waste streams from other producers and users ofthese materials. Gienntehrealfloyr,mtohfe PwaFsOtSesitgseenlfe,rbauttedraftrhoemr itnhethmeanfuoframocftuhriegahndmoulseecouflaPrOwSeFigdhetrpioveldymmaetreircimaaltsearriealns,ot d`wehgircahdactoinotnaoifn stmhaelploalmymoeurnitcsosfubrsetsaindcueasl imsovleercyulceosmwphliecxhanmdayeffboertpsreacruerusonrdsertowaPyOtSo.undTehrestand. the mechanism and the extent to which they may degrade to PFOS. iFnrtohme tfhoersmotafndspooliidntwoafstwea,stwehitcyhpei,sacpiptrheorxiimnacitneelryat9e0d%oorfditshpeowseadsotfe giennlearnadftieldls.froTmheallresmoauircneisngis wastes are discharged as wastewater (~9%) or will improve the understandingof the possible as air emissions (~1%). mechanisms associated Several ongoing studies with environmental fate and transport of PFOS. (See Appendix IV.) `aTrheebeexipnogsduerteepromtiennetdiatlhfrrooumghwaassteerigcesnoefrmaotniiontosroiunrgceesffaonrtds.actFuoarl eexnavmiprloen,meantmaulltcio-ncicteyntsrtautdiyonwsas duepstiagkneeidnttoo foobotdasi,nainndfoprrmeasteinocneaibnosuutrtfhaecediwsapteerr.sioTnhofefpluuroprooscehoefmtihcealsstuindyth,ewhenivcihrohnasmebnete,n iannidtieactoedlobguitcanlotexcpoomspulreet.edW,hiesrteo ipomspsriobvlee,tshaemupnldeesrswtearneditnagkeonfotrhewiploltebnetitaalkseonufrrcoesmotfhehsuumrafance wtoatpeurblciocllyumonwnaendd sturrefaatcmeenmticwroorlkasy,ers,lusdegdei,meanntd,lrainvdefrilflislhe,acdhraitne.kinAgddwiattieorn,ailnlfyl,ueant"maanrdkeeftfluent dbeafsikneitt"ivoefseexvpeorsaulrefoanoadlypsriosd.ucTthsewislulrfbaecesawmaptleerd.coTlhumendadtaatafcroolmletchtiesdstasudpyarwtiollftphriosvisdteudaymwoerree used to create the Initial Assessment for the Environment (Section 3.3.1). raf nin sscssmen Repo Pr0S 000018 Tinwvoolovtehsear gsltoubdailesbairoespuhnedreermwoanyittoorcihnagrapcrtoergirzaemtaheimeexdpoastuurnedpeortsetnatnidalinogftPhFeOdSi.strTibhuetifoinrsotfstPuFdOyS. OinfaPFvaOrSieteyxopfoosrugraentiostmhse,sesourcghaansismmasm.maIlnst,hisfiassh,seasnsdmebnitrd,s.thTisheisnefodramtaatipornoviisdceoambdiirneecdt mweitahsutrhee orfestuhltosseofexepcoostuorxeisc,oliofgaincya.l Ttehsetidnigsacunsdsimoanmomfalthieanfitnodxiincgistyfrtoesmtitnhigstboiuonsdpehresrteapnrdotghreapmotaenndtiraelsurlitssk ofecological effects studies are presented in Section 3.2. `ATlhaebsaemcao)n.dSsatmudpyleissobfegirngoucnodnwdautcetre,d siunrtfhaeceviwcaitneirt,y soefdaimmeanntusf,acatnudrfiinsgh faancdilbitiyrd(Dsepceactiuers,have bcoenecnenctorlaltecitoends ainndpraongarleyssseisvearleevienlpsroofgrtehses.foTohdiwsesbtuadnyd,wiilnlcaolnsjoupnrcotviiodnewiintfhoortmhaetrioinnfoonrmPaFtiOoSn, will be used to develop an analysisof the biomagnification characteristicsof this compound. Exposure and Release Management 3prMiorhatso tahlarteaadnynoaunnncoeumnecnetd,tsheavteirtawlilalctvioviltuinetsartiolryecdeuacseetphreowdausctteioanondfePmOisSsFiocnhsemfirsotmry3.MEven pmraoncuefsasctuunrdienrgstoapnedriantgiohnasveanbdeteoniemnphraonvceedp,rothdeucltevqeulaolfitryehsaidduablesenanidmpwlaesmteenstefdr.om Ptrheoduct and omfanturfeaactmteunrtinegquoippemreatnito)n,smhoasvtefbleueonrorcehdeumciecdal(tshorliodugwhasitmeprmoatveerdiaplrsocfersosmc3onMtrmolasnuafnadctiunsrtianlglation rheacveeivheadthaenrdmawliltlrecaotnmteinntu,eatnodhtahveeparosiggrnaimfoifcapnrtoidmupcatctphoansree-douuctiinsgutnhdeerewxapyo.surAelpootfentthieasle fsrteopms 3M manufactured fluorochemicals. 3.1.2. Predicted Environmental Concentrations (PEC) AdesritvheedSbIaDsSedMoannumaolniitnodriciantgesd,attaheanpdr/eodricctaeldcuelnavtiiroonnumseinntgalexcpoonsceunrtermaotdieonlso.r PAEtCthisshotuilmed,bet:he dPeFvOeSloapnmdentthoefopverreadlilctcihavreacmtoedreisltsicissofintaheveprryoedaurcltyssatangde.waTstheespihryesaimcsalm/achyemhiicnadlerprtohpeerties of dwehvieclhoaprmeennottofapvraeildaibclteifvoermtohidselcso.mpTyopuincda.llTy,hetshee mfoacdteolrssacraelrefoqruitrheedufsocropfreldoigctPinogr K,, factors, bioconcentration and, cannot be determined. becauseof the surface active properticsof In addition, the natureofexposure routes the compound, the factors would add considerable `complexity atmosphere to or the its developmentof these models. binding potential in ecological For example, PFOS degradation in the species or compartments such as sediments is nEontvifruollnymeunndte,rsistoboads.edCoonnsaecqtuueanltmloyn,ittoherianngaldyastiaswphriescehntaered liinkeSleycttioobne3.m2o,rEeffreecltisabilne tthhean modeling estimates for this compound. rat ital sess Report PFOS 10 000019 tDhaetsaeadraetaavaanidlatbhlee efxrtoemnstihveemeuclottio-xciictyolsotguidcyalanadndthaenigmloablatlebstiionsgphreesrueltmso,ntihteoprriendgicptreodgram. With `ecnovimrpoonumnedntcaaln cboenctehnotrroautgiholnysc(oPmEpCasr)eda.ndThtihse pirnefdoircmtaetdionnoiesfpfercetsecnotnecdenitnrtahteiofnosl(loPwNinEgCs)ecotfiotnsh.e 3.1.2.1 Surface Waters PStFrOauSssc,o2n0c0e0n)t.ratFioornscaicnhscuirtfya,cae lwiastteorfskweeyr3eMansaulpypzleyd cinhasianmcpulsetsofmreorms swiaxscigteineesr(aNteids,hiaonkda tahned locations of the customers were determined. identification of surfacewaterbodies in both Examining the various locations resulted the upstream and downstream vicinityof in the the key 3POMSFc-ubstaosmeedrsm.anTuhfaecltoucraitnigonasnwdefrleucohroocsheenmitcoailntuesgerabtye tkheeypsoutepnptliyalchPaFinOSsouerxcpeos.surIendaudedittoioanl,l a "aqnudieltocwaattieorns" asriteecwoanstalionceadteidn tathecascthudcyitdyeseixgcn.eptAfodreCsclreivpetliaonndo,ftTehnenessitseese.forDeetaacihlsciotyn itshefosuitneds in Table 3-1 Aprteseeancthsctihtey rseasmupltlsinofgthsiete,latbwoorawtaotreyransaalmypsilse.s wAerseiteanaavleyrzaegde faonrdPaFmOaSxciomncuemntvraatliuoena.reTable 3-1 ptarbelse.entTehdefoarveeraacghecaitnyd. mTahxeirmeupomrtvianlguelismiatrse ausneddmientthhoedrdisekteacstsieosnslmiemnittsaanraelyisnedsicparteesdenintetdhein Section 3.2. Lucie 2,930 The largest concentration parts per trillion (ppt) and of PFOS was found in the quiet the second largest at Decatur surface (114 ppt). water The in Port St. c2o5npcpetn.trOaftitohnossoefcPitFiOesSwiatthClaevveerlaagned,PTOenSnecsosnecee,ntwrearteioanlsl glresesattehranthtahnetlhiemirtepoofrqtuianngtilifmiicta,tion of CPeonlsuamcboulas,, FGleoorrigdia,a,hhaaddthtehesmsaelcloensdt ldaertgeecsttabalveeraavgeeraPgFeOPSFOcoSncceonntcreanttiroantoifono80f.205p.p7t pwpht.ile `uTnhdeeransatloyotdicbaultafirnedcionngssiodfertheedPtoortbeSta.nLauncioemaqluiyetinwtahteermuslatmi-pcliitnygdalotcaasteit.on TahreenPotFOcoSmplleveetleslayt twhiitshsoittehearreficnodnisnigdseraatbPloyrthiSgt.heLructihea.n Tothheersaqmuipeltinwgatseirtesiisteasrienlatthievesltyudsymaalnldaanrde sntoatgcnoannstisptoenndt about 200 styrofoam feet and by 200 feet. bottles. The pond contained considerable manmade debris including plastic, 3.1.22 Biota `STahmepblieosspohfebrleoomdo,niltioverri,nagnpdrootghrearmtiwsassuesdweesirgenceodlltoecatsesdesfsrtohmeagrlcohbiavleddisstpreicbuitmieonnsoof PfaFOvSa.riety of species from several (the Great Lakes and locations and analyzed for coastal marine locations), PFOS. Areasoffocus the Arctic, and Europe. included North America Analysesof these s(faimsphl-eeastiinngd)icaantiemdaltsh.atTPaFbOleSsi3s-p2reasnednt3-i3n sthuemmliavreirszeantdheserresaoulftsoafnitmhaelss,e easnpaelcyisaelsl.y Tinhepihsicgihveosrtous average concentrations of PFOS in biota was found in the bloodofbald eagles and the liver of rap ilAssam Repr POS u 000020 minks. 4). Average concentrations in other tissues and other species were relatively lower (Table 3- eCnovnicreonntrmaetnitoanlsoexfpoPsFurOeS. mIenaslaubroerdationrybltoooxidcaitnydtleisvtesrowiftwhirladtlsifaendapmpoenakretyosb,ePvFalOiSd mweaassufroeusndofto dsiesrturmibuPtFeOtSo bvlaoloudesanidnclrievaers.edInalam2o6st-wleicnekarclaypsatuldeosteoxsicuiptytostaubdoyutwi1t0h0Cpypnmo,maolltghuosugmhonskeeryusm, `lgeevneelrsadtiiodnnroetpirnocdruecatsievelisntcuadrileysatinhriagths,ersedorsuemsa(nTdabllieve3r-c5)o.nceInnir1a4t-iwoeneskaldsioetianrcyraenasdetdwo- aadpmpirnoixsitmearteedlydolsienewaralsy fwiotuhnddoisnebl(oToadblaen3d-5l)i.verI.naThruadsi,olparbiemlatsetuadnydtrhaetmsatjuodriietsyinodfitchaete that serum PFOS concentrations resulting from directly proportional to cumulative dose up daily exposure over a broad range of to serum concentrationsof100 ppm PFOS doses (see section are 43.12). 3.2 Effects on the Environment 3.2.1. Effects on Aquatic Animals from Exposure to Aqueous Concentrations Saqiunacteic19o7r4gannuimsemrsohuasveacbueteenancdoncdhurcotneidc (tToaxibcliety3-t6e)s.ts Ouvseinrgtahisvatriimeet,yopfrforteocsohlwsatfoerrcaonndduecsttiunargitnhee tPoFxiOcSittyoteasqtusathiacveorcghaannigsemds. hFaosrbeaegnivdeenmtoynpsetoraftteedsttoanbde wteisttheinndaporienlta,tihvoelwyevsemral,lthreanegfef.ecTtaobfle 36tesstuemnmdaproiiznetss tahree aavqauialtaibclteoixincciltuyditnesgttrheesuElCts10th,atECarSe0cuorrrEenLtSlyOaovraiLlaLbSle0. oAr LvCaSri0e,tyLofOeEffCeactndlevel `EsCu9m0m.ariNeos effofreectaclheoveflsth(eNtOesEtsCsahnodwNnOiEnLT)abalree3a-l6s.o aOvnagiloaibnleg.aAnpdppelnadninxedITacqounattaicintsoxtihceirtyobtuesstt results are presented in Appendix IV. ExaminationofTable 3-6 shows calculated from a 47-day chronic that test the lowest of fathead NOEC found was 0.3 minnow conducted in mg/L 1999. PFOS, which The value is ergepgrseasesntthsettheestPeFnOdpSoicnotn.cenItnrkaeteiponinagt wwihtihchthneoSeIfDfeSctapwparsoafcohunodfuussiinngg athpeosmto-shtatscehnssiutrivvieval of indicator of PFOS aquatic species. effect as the PNEC, this report uses 0.3 mg/L in the risk assessment for 3.22 Effects PFOS on Terrestrial and Aquatic Birds and Mammals from Bioaccumulation of tIonxsiictiutayteinodnspowihnetrseisspaenciafciccesppteecdiepsraecftfieccetsindaetcaolaorgeicnaolt raivsakilaasbslees,simnetnetr.-spTehceiemsaegxntirtapuodleatoifonthoef ufnecweerrtasitnetpisesarienisnuvcohlveexdtrianpotlhaeteixotnrsaipsoluantkinonowpnro,caesnsd,ctohueldunbceerltaarignety(Cwihlalpbmeanlesest (al.S, am1p99l8e).et aIlf., e1x9t96r)a.polFaotrinPgFfOrSo,m omraamnmyaoltshetrocmhaemmimcaall,st(hce.gs.e urnactesrttoaimnitnieks)sahnodulldarbgeerswmahlelnerexwthreapnolating from mpraemdimcatlinsgteoffbeicrtdssof(c.cg.h,emriatcsaltos coanglbeisr)d.s Aandpomteanmtimaalllyslcarogmeessoufrrcoemotfheunvcaerritaabiinlittyyaassssoocciiaatteeddwwiitthh Lr -------- n 000021 sceonmsimtoivni,tyraelmaotinvgelyspceocniseisstteonttoxteisctcehnedmpiocianltss.fToorxhicuimtayndahteaalftohrrliasbkoraastsoersysmraetnstrtehpartesceanntbtehe most athpepliinecdretaosteedrreexsttrriaaplovlearttieobnrautnecse.rtaTihnetsieesemnednptoiinotnsedwialbloavles.o bUeseapoplfaiedtitsosbuircdonscpeenctireastisounbjoefct to PphFaOrSmacraotkhienretthiacnvaanrieaxblteesmatlhatdoesxiesetsbteimtawteeenresdpuecceisest.hiAs vuinacenrctahirnotnyicbysteuldiiemsinaarteinaglssooumnedoefrwtahey to better characterize the effectsofPFOS in birds. TchhreonpirceleifmfiecntasryofrePsuFlOtsSofonthrraetes arnecdenmtonsktuedyise,s w(sheiecThaibnlcel3u-d5e)d emveaalsuuarteedmetnhtessuobfcPhrFoOnSic or concentrations in serum and liver. As explained above, these results provide the best available information for characterizing the potential effects and risks of PFOS to piscivorous wildlife. Sraetcst.ioGnroCwotfhTaanbdlere3p-r5odpurecsteinotnsatrheetryepsiuclatlseondfapogirnotswtuhseadndinreepcrooldougicctailonrisstkuadsysceossnmdeuncttse,dawnidth ohfavteheatdaibrlceetshecoowlsogtihcaatltheeffNecOtsEcLororcecluartiroendaatttthheei0n.d4ivmigd/ukagl/adnddopsoipnuglaltevieoln. lNeovelt.oxEicxoalmoigniactaliloyn iprmep-oirmtpalnatnetfafteicotns loonsspiunpcrseuarsveivdaalnodr lgirttoerwtshizeo,ccpuurprevdiaabtiltihtiys, dgorsoew.thA,tan1.d6smugr/vikvga/lddaecnrdehaisgehde.r, For the ecological risk characterization for piscivorous wildlife, the NOEL from the dam pre- cmhaotiicen.g gFirrosut,ptwhaissvcahlouseeni.s taTkheins fvraloumeaisst4u7d.y1o-npprmepsreorduumctPiFonOSw.hicSehvhearsaldirreeacstopnospsuulpaptoirotntlheivsel rdeelreivvaendcef.roSmeacdounldt,, ntohnepmraegmnmaanlt asneirmuamlsv.alTuheisrdf,roemnd3Mge'sstabtiioosnpvhaelrueepsraorgeraafmfeacrteedgebnyertahlely physiologic changes occurring during pregnancy, introducing greater intra- and interspecies vnaeroinaabitlailtys.eraInaraedddiitfifoinc,ultfettoalcvolalleucets, taennddtthoebreismkofroer cuonncteartmaiinnattihoann oardudlitluvtailounesd,urbiencgaucsoellection `isnuhimgbheerr.wa(sNontoet: usTehderbeeciasuaseNOitEdoLeosfno6t2r9epprpesmenitnaSercetpiroonduBcotifveTaebflfeect3)-.5 Ffoorr ftehmeaelceolroatgsi.caTlhriissk characterization for serum PFOS NOEL piscivorous wildlife, the was used as the PNEC 0.4 mg/kg/day concentration. dam pre-mating valueof 47.1-ppm `Two recent studies were done to assess human health effects related PFOS toxicity to liver dcioentcaernytrsattuidoynsw--ithherat2s.6-Iwneethkec2a6p-swuleeektomxiocnitkyesytustduydwy,itthheCymneoamnoNlgOuEsLmofonrkleiyvseracnodnctehnetr1at4i-ownese.k omfeaPnFO(Smalatetahned0.f1e5mamlge/kavge/rdaagye)doNsOeEwLasfo8r0lpipvemr,co(nTcaebnltera3-t5i)o.nsFfoorrtPhFeO1S4-awtetehke r2a.t0sptupdmy,dtohsee wPaNsEC72s.5foprpmth.is(iTsakblaess3e-s5)s.menEti.theTrhteheramtolnikveeryvallivueerwvaaslucehoorsetnhefroarttlhiivserrivsaklausesceosuslmdenbtebuesceadusaes it results in the most conservative risk estimates. concentration was used as the PNEC. Therefore, the 72.5-ppm liver PFOS rat nia sso Report PFOS 000022 3.3 Initial Assessment for the Environment Effects to the environment are calculated mammalian assessments. As indicated in using a ratioof the PEC the SIDS manual a ratio to PNEC for both aquatic ofgreater than one (>1) and iidnednitciaftieesdaasnpdectihfeicchheamziacradlmcaayn bbee cpoosnesdi.derAedrattoioprfeasrebnetlaowloownepo(t<e1nt)iianldfiocratreisska. hInaztahrisd cannot be eaxspsleiscsitmleyntinaccotrupaolraetnevdirionntmheentPaNlEdCa'tsa aorreruisskedcatlocuelvaatliuoantse. rTishkeainndvesrasfeeotfytfhacetorrisskarreatnioo,tor PNEC/PEC, is the marginofsafety. `Ignraapdhdiictailonfotromca(lFciugluarteisng1,th2eaPnEdC3)./ PThNeECgrarapthiiocss, pthreoveifdfeectasmaentdhoedxpfoosruvriesduaaltlayacroemppraersienntgetdhien eefxfpeocstsuraendcoenxcepnotsruarteiodnast,a.thFatroarme tchoentgarianpehsd,inthteheracnugreroefntefdfateactssetcocnacnenbteraatsisoensss,edo.r rCaunmguelaotfive afsrseeqsusemnecnytsd,isatrnidbuptliootnssofotfheeffedcattsaaanrde eprxepsoesntuerde.arUenclriekaetetdhefoPrEbCot/hPthNeEaCquraattiicosawnhditcehrrefsotcruiaslornisk othfethheigphoetsetntpioaslsirbilske orfisPkFeOstSimaactreos,sstthheegernatpihriecarlanagpeprofoeafcfhecptrsovainddesexapcoosmuprreeihnefnosrimvaetiaosn.sessment 3.3.1 Risks to Aquatic Biota from Exposure to PFOS in Surface Waters c`Toanbcleent3r-a7tiproensseanrtes atvhaeilraabtlieo.ofTPhEeCrattoioPsNraEnCgefforroeamc0h.o0f00th0e16ciattiePsorint wSth.icLuhcaiqeua(tSiitcee2x)ptoosu0r.e0096, faolrsothaet PquoirettSts.urLfuaccieew(aqtueiretsasumrpflaeceinwaDteecra)t.ur.TheAlslebcuotndonlearogfetshteratriaoti(o0s.i0s0l0e3s7s)thwaansodneetebrymianed mmaarrggiinnooffssaaffeettyyogfreoavteerr t1h0a0n. 20A00c.omTpahreiqsuoineotfawaltlertoaxticPoolrotgiStc.alLuecnidepoiisntthseteoxcteheptmioanx,iwmiuthma iPnFdiOcSatceosntcheanttrfaortitohne ocbutrareinnteldyaatveaailcahbloefwtahetesrixccoiltuiemsnisdasthaotwhne cinonFciegnutrreat3i-1o.noTfhPeFFOiSguirneall usnacmeprlteasinatrye(wbealsledbeolnowthitsheveerntyicroenrsaenrgveaotfiveecortioskxiacpoplroogaiccha)l, etfhfeecctusrrdeatnat.inWfiotrhmiantitohneibnoduicnadtsesofthat I1t0sahdovuelrdsbeeefrfeeccotgsntiozeadqutahtaitcabqiuoattaicwoeuxlpdosbuereasdsaotcaiisateldimwiittedh.measured concentrations of PFOS 3.3.2. Potential Risks to Terrestrial Wildlife from Bioaccumulation ofPFOS tAlhlanPoEnCe/(PTNabElCesra3t-i8osanfodr3b-l9o,ordesapnedctilvievleyr)P. FOThSescoentcaebnltersatpiroonvsidien treartrieosstrfioarlcoarcghansipescmisesweurseinlgess atvhaeillaobwleesttiisssuseusacomnpcleenst.raTthieonl,artgheestmmaaxxiimmuummtirsastuieocfoonrcPenFtOraStiionnb,laonodd twhaesa0ve.r0a5g5e2offoarlblald bealgoloeds.coTnhciesntrrataitoiornesproefsePnFtOsSt.heNdoetgeretehoatfrtihsiks raftoirotrheepriensdeinvtidauamlaeraggilneofwsitahfetthye hoifgh18e.stTmheeahsiugrheedst Mmeeaann rPaEtiCo/isPaNlEsoCarsastoicosiawteerdewiletshscfaogrlaelsl (o0t.h0e0r7s3p)e,ciaensd. represents a marginofsafety of 137. rat nin sss Report PROS In 000023 PFiFgOuSrec3o-n2cecnotmrpaatiroensstfhoerPalNl EspCecfioersssearmupmlecdo.nceEnatcrhatviaolnuewiitnhtthheeccuummuullaattiivveeddiissttrriibbuuttiioonnoisftbhleood amneaalynsoifs.allExsaammipnlaetsiofnoorafptahrteicfuigluarresspheociwess.thLaatbtehlesmoenditahne PfiFgOurSe isnedriucmatceotnhceenstpreactiiesonusfoerdailln the Species is approximately 0.03 ug/ml. The 5" and 95 percentile PFOS serum concentrations are oapnplryo5xi%moaftetlhye .s0p0e4ciuegs/mm!eaanndP0F.O28Susge/rmlu,mrceosnpceecnttirvaeltyi.onsIneoxtcheeerdw0o.r6d4s,ugb/amsle.d Foingucurrer3e-n2t dsahtoa,ws that for the currently available environmental data the serum concentrations of PFOS in wildlife samples are well below the PNEC. For PFO in liver, the largest maximum PEC/PNEC ratio was 0.0676 for the mink with the highest liver concentration. This ratio represents a margin of safety of 15. The largest mean aPpEpCr/oxPiNmEatCelrayti5o9.isFailgsuoreas3s-o3cicaotmepdawrietshtmhienPkNlEivCerf(o0r.l0i1v7e0r),cornecperntersaetnitoinnatgomtahregciunmouflastaifveety of dairseturisbeudtiionntohfe icvuemrulPaFtiOvSe cdoisntcreinbtutriaotni.onsExfaomrianllatsipeocnieosfstahempfliegdu.re Asghaoiwns,tshpaetctihees mmeedainanvaPluFeOsS cliovnecrenctornactenitornastairoenafpoprraolxlismpaetceileys 0is.0a2ppurgo/xgimaantde0l.y40u.g0/8g,ugr/egs.pecTthiveel5y*. anFdig9u5r"ep3e-r3ceinntdiilceates that for the currently available environmental data the liver concentrations of PFOS in wildlife samples are well below the PNEC. Tmihnek.remFaoirneixnagmsppleec,ietshehasveecoPnEdCh/igPhNesEtCmraatxiiosmtuhmatsaerreummurcahtiosmiaslalsesroctihaatnedthwoisteohfheeargrilnegsgaulnld S(0e.r0u0m46c)o,nrceepnrtersaetnitoinnsgisa 1m0a,r0g0i0nofforsatfheetnyoorfthe2r1n7.fuTrhseeallaargnedstthmearstgeilnloarfscsaafleitoyn.foIrntlhievemra, xthiemum osfecsoanfedthyoigfhe7s3.t mTahxeilmaurgmesrtatmiaorigsianssoofcsiaafteetdywfiotrhthtehemraivxeirmotutmerl(i0v.e0r1c3o7n)c,enrterparteisoenntiisnsgeaenmairngin swordfish (5,000). Sourcesof uncertainty in these risk characterizations include the following: 1. The relative sensitivities of rats, monkeys, and piscivorous wildlife species to PFOS are unknown; therefore, using rat and monkey laboratory PFOS toxicity data to predict cefofneccetnsttroatpiiosncoifvoProFuOsSwirladtlhiefretmhaanyaonveerx-teorrnaulnddeorseesteismtaitmeatreisrkse.ducUesseothfisatuinscseurteainty by eliminating some of the pharmacokinetic variables that exist between species. 2. The amountofchronic toxicity data for PFOS available at this time for predicting risks to piscivorous wildlife is limited 3. cTohnecednetgrraeteiotnoswihnibclhoothdealnidmiltievderdaintapiinsctihveorboiuosspwhielrdleisfeamaprleirnegprpersoegntraatmivfeorofPPFFOOSS. concentrations in piscivorous wildlife in general is unknown. In summary, it can be concluded from currently available data that the observed levelsofPFOS ofrrotmheaewnividreonvamreinett.yofPEsaCm/pPlNeEsCcarnantoiotsbaereasssuobcsitaatnteidawlliythleisdsentthiafniaobnlee a(<d1v)e.rsIet esfhfoeucltsd bien:wildlife Dra itlsess Report PFOS 1s 000024 srteucdoigensizaerde,uansdienrdwiacyattehdatabwoivlle,intchrateausnecetrhteaainmtoyunextiosftsdiantathaisvaainlaalbylseisf.orAcdhdairtaicotnearlizaivnigarnisckhrtoonic. birds. Finalizing biosphere monitoring studies also will provide more information on the presenceof POS in the environment. 33.3 Other Effects ``Smtaannudfaarcdtiuzreidngwhploalnetelfofclauteendt itnoxDiecciatytutre,stAslraeqbuaimraedwuenrdeerretvhieewdeids.chaQrugaertpeerrlmyittesftorintghewith Daphnia and fathead in the test organisms minnows is required. exposed to the plant For the effluent, past two years, there has been which does contain PFOS. 100% survival Dra ntl sessReport PROS 1 000025 Table 3-1. Environmental Concentrations (PECs) for PFOS in Surface Water PEC (ng PFOSIL) ppt Location | Sampling Site Si]te Average| 0L%ocHat0ioonn Coumbus, |_ Stel |@8|so| oo | Georgia [sea |766 | wa| ow | singin | removes| Stes |534 Quitsurface| <25 | | ssa <25 | ssa 25 | water 53 Pensacola, Florida ["siez | 28s|28| a7| sE earnmp cean[s suQui:eetsusrtice|| 01597 [|181s74 | 11766 | ves water 25 Vole, |sel | 230| 2| 8 | aba [S | 96|i ws|z az| [-- rerscioms ["Ouictsurface| 333 | 31S 24 rie water Decatur, Mabam-- a [S |ws|i 2 |z wa | eeervaroer s| QuieOt srurface 11 i a Cleveland, |_ste1 |147 | <25[199 | Tennessee SEfimriinees os fcloopriindgaocsinsin [iebeaeat| Sues | 78| sa | 66 | rFiSenTrons || QQuiSctsourrface| 2930 | 2850| 289% Limit ofquantitation s 25 n/L and method detection int 1s 2.5 ng/L. Ort ntl Assons 05 20% w 000026 Table 3-2. Environmental and Serum Concentrations (PECs) Samples from Wildlife of PFOS Species in Blood, Plasma, NSuamplmberof " PEC(Luog PFOS/mL) anodarT CaspianSeal |14| 0012 | 0018 | 0013 erg G3 |ooos|oss|om| on | No FurSear l] 4e| 00058" | 00058"| 0.0058"|00| rw | 1 o[woow [ow[vo 0 |o-w| Stellar SeaLion 0.00587 | 0008 | 00058 |00| *Level of Quantification for the * The mean concentrations were Specific Analysis calculated using all data points, including those that were below the limit of quantification. Dra itAssent ReportPEOS i 000027 Table 3-3. Environmental Concentrations (PECs) of PFOS in Liver Samples from `Wildlife Species Rie ee Somer 15[ows `Samples [om Joon on | Deviation [[b aBwomwarreoenn o 1 [20T[oowoi owror_||oootmm [[[wos ooirare|||oosrocsos|]| [GiCnaomaSsamatrion | 6 |ooom ||ooowm [aooast|[_oaoooesrs|| [Bsa --5 oow |owsos] 0 | Gow [on[os [on]-| fo[ ore s ||ee 5T|oooe mmwe[|[ooovmwr r[[Jooooims||s ]ooooann|] Me ow |ww [a]ii] SoRs roosbcewor [| +o 1[voons||| oovowws s[[Jooomwss|||oo0xi]_]| pedo + ots |ore [om[ow_| fFraaam 3 | oooo [|oooz |Jooomns|| w0ow|| ET I NERSCE 000028 *"LTehveelmoefaQnucaonntciefnitcraattiioonnsfowretrheecSapleccuilfaitecdAunsailnygsialsl data points, including those that were below the limitofquantification. Table 3-4. Envir`oSnammepnlteaslfCroonmcePnitsrciavtoiroonuss(WPiElCdlsi)feofSpPeFcOieSs in Other Tissue Species Tissue Number of Samples PEC (ug PFOS/g) ppmStandard Deviation on Chinook [sCaolmmoonran 0.0070 || 3[wow |om[ow|onn_| muscle, 0017 | 0024 0.0027 whole body Soro | on[2[o|mooe [ows| 0 | *TLheveelmoefanQucaonntciefnitcraattiioonnsfowretrheecSapleccuilfaitcedAunsailnygsiasll data points, including those that were below the limitof quantification. Dra iilAsssmes Report PFOS 0 000029 Table 3-5. PFOS Toxicity Data for Mammals: Observed Effects, Serum and Liver PFOS. | Concentrations, and Cumulative Observed Dose Serum PFOS| Liver PFOS| Cumulative Group! | Etteet Concentration|Concentration| Dose (ppm) (ppm) (mg/kg) 26-week Capsule-Dosing Study in Cynomolgus Monkeys [omggd NOEL | 8Ts 273) hepatocyte enlargement females males mee 0.75 mg/kg/d Dfoerat2h/6omraelaersly sacrifice 14-Week Dietary Study in Sprague Dawley Rats [Z5o0ppppmmFeMmalaelses [N[HOepFatLocellular | vacuolization > 100, <137 eo] 386.a5s3 244) 20 ppm Males == I |Hepatocellular hypertrophy and vacuolization; decreased cholesterol; increased. AAT hypertrophy and vacuolization 599.94] I pares ow 0.4 mg/kg/d Dam |NOEL PM EG 04 mgkgd Dam [NOEL EG T6 mg/kg/d Dam |Slightbodyweight PM T6 mgkgd Fetus |Survival, body weight EG Dv ni ssnReportPFOS arr] 7] 47.125.00 (n= 1638] 16) 05) 3ET0m= BE 3] 6) 1855140 (n= GE) 16) | 117% 14.5 (a2) = NA 2 0000350 Table 3-5. PFOS Toxicity Data for Mammals: Observed Effects, Serum and Liver PFOS ~ I Concentrations, and Cumulative Dose Observed `Serum PFOS | Liver PFOS | Cumulative [Grow re Concentration |Concentration| ~~ Dose | (ppm) (ppm) (mg/kg) arespr[e Fwes e [| e]nM EG 4 3P2M mg/kg/d Dam [Body weight 3166)8 23.6 (n= 134] porepm [gee] [7 EG 6) paren [per Jee] 1H EG 6) + PM = Pre-Mating, after 42 days of dosing; and EG = End of Gestation, day 21 ofgestation Dv nilAsseRnotr POS 2 000031 Table 3-6. Aquatic Species Ecotoxicity Tests with a Survival Endpoint Using PFOS [BTo ow]|Dasppe |emmAeowreac|n|Fsenen co-s || (199 | Doman | Aowe |_seneco=o_| FBT 919o9 ||pFuavmeasmiamgimnoan|| Aomwee ||_o6zheincesc0s=-0o5r|| [Fm| vows | ene | sohics=30| [(50119% || DFaobsmomamnon || S03 1996 | Fain| oonwee ||oscehnnEosr=Ln<00|| Aww | seni0=50| ffroor||DFaemiann[|AwAeewe || sseenincsci-en|] [o0o17o | Fapeesattmiimonn|| Aemwee || vSeennicsoon|| [9_|Ftdmon| Chrome _|_sranorc=0|" [[5to7w||FVootwmmon|| GChnon ||_Spaaonroce=c0=51s|| = * Bold indicates the value used in this risk assessment. -- . 000032 Table 3-7. Aquatic Species PEC/PNEC Ratios for Six Locations PECYPNEC Ratio Loccaattiion [ser] Site Site3 Quiiet Surface Water Pensa, FL_| 66x10"|86x10'| ooxio"|sexi] Six | sr Cleveland, TN | 66x10| 83x10 |83x10 = | Port St. LucieF,L |_1.6x10| 28x10 | 22x10 96x10 + * TSihtee vaavleureaguesePdECas, tihneuPniNtsEoCfinsg0.P3FOmSg/LP,FOpSrIeLse,ntbeadseidn oTanbslteud3y-1.reference no. 78 amseapsreusreendtevadluien.TaSbalfeet3-y6.facNtoortseatrheatnottheusvealduien0t.h3emcgalcPuFlaOtSi/onLoifs tahneactual PEC/PNEC ratio. Dr nidsss Repor POS 000033 Table 3-8. _Piscivorous Wildlife Species PEC/PNEC Ratios for Serum pron om Tv Ratio ] [Mi |n Maxii mum| mu Menm| f[ or Po oom r | ooooorrr i_|_| ooo omme_]| Sense Ton * Minimum, maximum, and mean PECs (ug PFOS/mL) are presented in Table * The " St 5 the PNECfo serumis 47.1 megor ug. Dv tilAssam Report PROS x 000034 Table 39. Piscivorous Wildlife Species PEC/PNEC Ratios for Liver --_ Ratio [Rims [Moiwveimsum[|woMaoxismum| | oMoeann || [b Ganges oo | om wn | s soon | Csewhies--oo|o|o_oowom s| Fruie--o--w--|o_o ooou 2_| 2) b) Minimum, maximum The value used as the and mean PNEC for PEC's (ug PFOS/g) are presented liver is 72.5 ug/g (Table 3-5) in Table 3-1. Dra itl sessmentReport PFOS 000035" 1T EE soerrnBE e088+ + won| ee ra--fis-- che-- ri -- ls imi | a Fp Cai oerae tee ricn l + emt [tio I Ee FO] asreimna5e] airneels + Toros foul | - Lo weeeen. | or i ----------+ parvo - mon| | ee ee + FrmauninRcaonNE | . I la + SeseenrdeoeeG:o nEe + Fausrma t | Canantoniots Figure 3-1. Cumulative frequency distribution of aquatic species ecotoxicity test results. [Note: Cumulative frequency of the ecotoxicity test results is calculated by first ordering the data from lowest to highest, while keeping track of the order number. The order number is then divided by the total numberof observations and then converted to a percentage. The resulting cumulative frequency is a value that ranges from 0 to 100 percent.] Pr -------- n 000036 -- | += EE | i - 3 . Coe | on ha... J | -| * sowie. ~_ BN | we enim | Figure 3-2. Cumulative frequency distribution of mean PFOS concentrations in blood samples of piscivorous wildlife species. [Note: Cumulative frequency of the exposure results is calculated by first ordering the data from lowest to highest, while keeping number trackof the order of observations number. and then The order number is then divided by the total converted to a percentage. The resulting `cumulative frequency is a value that ranges from 0 to 100 percent.| tt sme tn 5 o 000037 Ton] i [a 3: A Co | | ae SO ie - se ro E - samme ae ros comment = I - - . 7] 1 Figure 3-3. Cumulative frequency distribution of mean PFOS concentrations in liver samples of piscivorous wildlife species. [Note: Cumulative frequency of the exposure results is calculated by first ordering the data from lowest to highest, while keeping track of the order number. `The order number is then divided by the total number of observations cumulative frequency is a and then value that converted to ranges from 0 a percentage. to 100 percent] The resulting Ort et sme pa 70S 000038 * 4.0 HUMAN HEALTH 4.1 Introduction This section contains a summary ofthe available data relating to the potential for PFOS to induce adverse effects in humans. The available data consist ofa large body of epidemiological, animal, and other types response data now exist ofexperimental relating serum data, levels reported over the pas to adverse outcomes t i 25 years. Substantial dose- n experimental animals, including primates. Included are repeat-dose studies, two-generation reproduction-development studies, teratology studies, and genotoxicity studies. Still in progress, and not reported here, are 2c0h0r0o.nicTahneimmaajlosrtiutdyioefsc;irteastuilotsnsfrinomthtihseSseecltioonng-atreermfrboimoasstsuadyiseswialnldbreepaovratislafbrloemby3Mthespeonndosofred work, the detailsofwhich are found in Robust Summaries. These Robust `Summaries are contained in Appendix V ofthis SIAR. The authors ofthis section wish to acknowledge the effort of U.S. EPA scientists in preparing many initial Robust Summary drafts that werefurther developed and edited by the SIAR authors. The principle focus of allofthis work is PFOS. The toxicity testing program includes two. rmeeltahtyeldpceorfmlpuoournodosc,taNn-eetshuyllfpoenrafmliudooreotohcatnaonle sulfonamidoethanol (N-MeFOSE). The (N-EtFOSE) and N- structuresof these chemicals are shown below. Both are components ofcommercial products, and both are known to beabsorbed and undergo metabolism to yield PFOS. N-Methylperfluorooctane sulfonamidoethanol N-Ethylperfluorooctane sulfonamidoethanol FC, FiC "ory-cer,r crN,orpcrN,edbweeYoonnm \or-oFo,rc,NerpcrN, e4dndoYconhn,poH, Bothof these compounds have been subjected to repeat dose toxicity and genotoxicity testing, and the ethyl derivative has also been evaluated in teratology and two-generation reproduction sPtFuOdSie.s. TAhisswsiulglgbeestsseetnh,atbothteh tcooximcpiotiuensdosf pPrFoOdSucpereefcfuercstosrvmeorlyesciumlielsarmtaoythboeseduperotdouPcFedObSy accumulation as opposed to the precursor molecules themselves, or to anyofthe intermediary `metabolites leading evaluationof PFOS to PFOS. This serum levels in conclusion relation to can not toxicity be is verified until a careful quantitative completed. Thus, for the present, the data on the N-ethyl and N-MeFOSE alcohol derivatives is presented for completeness, and `because they confirm, at least qualitatively, the PFOS results. Ort it Assenpaot POS 000039 5 42 Human Exposure 4.2.1 Background TorhgeandiactafolunorPiFneOiSn lheuvmelasninsehruummawnasseorbusmesravmepdl3e0sayreearpsreagsoe.ntTehdeinadthviasnsceectmieonn.tofTahnealpyrteisceanlce of tcehcehmniisqtureyshdaesvhealdopaedsigannidfiucsaentd ibnyflrueesnecaercohnerksnionwtlheedg19e6o0f'sflaunodro1c9a7r0bosnwseirnehutimmae-ninsterean.sivTeh,e r"eoqrugiarniincg fhlouuorrsifneorcoamspionuglnedasn"al(yasniys.coTmhpeomuentdhohdasviwnegrfelugoernienrealcloyvanloennstpleycibfoinc,demdeatsoucrairnbgon) rdaetchreeratsheadnasnpaelcyitfiicctmiomleecfuolretso.talTohregadneivcelfloupomreinnetotofuanrdaepridananhaoluyrt,icaltleocwhinnigqulearigne-tshceallaetmee1d9i7ca0l' sourrgvaeniilclafnlcueoorfinper)otdhuacttwieorneeamdpelqouyaeteesfoart thhieghleervedlestefcotuinodnilnimoictcsup(aatbioounta0l.l5ypeaxrptsospeedr imnidlilviiodnuals. T1h9e90asd,varanpciedmaennatloysfischorfosmpaetcoigfircapfhliuco/rmocahsesmsipceacltsrforsocmopsymatlelchvnoolluogmyesenoafbsleerda,. bTyhithseteeacrhlnyology was first used in medical surveillance in 1993. Detection limits for PFOS in serum were lowered 10 50 parts per billion by 1997. "iiTnhihsusmeacntisoenrap;re2s)endtas:ta 1f)raobmri3eMf seummpmlaoyreyesoftinhveolhvisetdoriincaflluionrfoocrhmeamtiicoanlrpergoadrudcitnigono;rgaanndic3)flduaotriane: from various sources of humansera that may represent non-occupational exposures. Historical Finding of the Organic Form of Fluorine in Blood Traadvieosac(t1i9v6e8fal)uodreisncer-i1b8edantdwoonfeorthmastowfaflsunoorti.nePointhsaeprruamg,aodnaeetthaalt. w(1a9s71e)xcahlasnogdeeasbclreibweidthtwo ftooramlsb,umiionn.ic Tahnidsnfoinnidoinnigc,. alToanvgeswi(t1h96re8sbu)ltsshoofweexdtrtahcattiotnheannodnp-reexccihpiatnagteiaobnlaendfltuhoerinneeewdasforbound nasohniinognitco frleuloeraisneetwhiassf"oorrmgaonficf"l,uoirci.ne,colveadletnottlhyebcoounncdlutsoiocnartbhoatn t(hTeanvoens-eetxaclh.a1n9g7e6)a.bleUsoirng NpeMrfRluosrpoeoccttraonsociocpya,citdhe(sPeFaOuAt)h.orsThteenrteatwiaveslysoidmeentviafriieadtiaocnoimnptohneeonbtseorfvtehde sopregcatnriacffrlouomrainne as apurtehseenntciecosafampsluelfoofnaPteF,OwAa,shpoowsesivbelre,. leSaudbisnegqtuheentauetfhfoorrtsstboysu3gMgesrtestehaartchberrasncihdienngti,foiredtbhoeth PFOS and PFOA in blood. ASenrumufrmoomfbpsrteeusduirmesabolvyernotnh-eopcacsutpa2t5ioyneaalrlsyreepxoprotseeddlpeeverlssoonfs.orTgaabnliec4f-l1uoprrienseenitnshtuhmeasntubdlyood auustehdorf,orledveetlermmeiansautrieodn,ofpofpluuloartiinoenssusgtguedsitesdtahnatdsmoemtehocdasutoifonanbaelyusisse.d Tinheinvtaerriperteytionfg mreestulhtos.dsAll reported means were in the tens-of-parts per billion levels. The average of reported values from United States sources is 0.038 ppm. Def ni sssmen Repo PFOS 2 000040 Table 4-1. Historical Findingsof Serum Organic Fluorine Levels in the General FoPopVunelartiT|onowAuthor |[OoFoGenm|| Nes__[|AMwethoaTM|usSourse || [[919%% [BGeulyi.slTeaves [i979 [Singer || 00002250 || 1906_[OAbsohmb | 0085 |28 [Am [U[UsS [Us | | [{7r9o8w0 [|hPeaels [os Belise [0000s85||Foo4led|[AMsohdObomb[|AgUenSa || |_a0ri |_ [Obomb [Chim | 1989|Vamamom | 00% | 11__[LOPA Japan | * Organic fluorine, specific identities not provided. +x Varied methods were used to measure organic fluorine. See papers for details. 4.2.2 Occupational Exposures 3M manufactures `metabolize, to an uPnOdSeFt,eramisntaerdtidneggrmeaet,ertioalPFfoOrSo.thEemrpfllouyoreoecshemmaiycables that may exposed then degrade or by one or more routes (i.., inhalation, skin manufacturing environment contact/absorption, or ingestion) . The primary route of exposure to flu varies orochem among icals in the employees and dhyegpieenndes, opnersseovnearlalhafbaicttsoras,ndingcelnuedrianlgwporrockepsrsacctoincdeis.tioEnxsp,ojsoubretaesskts,imwaotrioknlhoacsatbioene,npeexrcseoendailngly difficult when multiple sourcesofexposure are probable. Biological monitoring data (e.g., salelreuxmpolseuverles)somuarcyesa.ddrBeisolsotghiicsaplrmoobnlietmoraisnigt daaltlaowasrefoerspaenciianltlerynraellmeveaanstuwrheemreentthaesyseresfslmeecnttdofsre:om to the target organ (e.g. liver). This is likely to be the situation for PFOS as it has been observed in cynomolgus primates that the liver to serum ratio is approximately 1:1 up to serum levels approaching 100 ppm (see section 4.3.1). "UTSaAbl)e,4A-n2tpwreerspe,nt(sBPelFgOiSums),eraunmd vSaalguaemsiohbatraainJeadpafnro[mRSp6la,ntRSeSm,plRoSy9]e.esTihneDeDceactautrur(AalnadbAamnat,werp plants are involved in fluorochemical production, whereas the Sagamihara facility handles, but dsourevseinloltapncreodoufcper,osduulcftoinoanteedmppelrofyleueosrobcehegmaincailnst.heAllattheo1u9g7h0'vso,lruonuttairnye`sbpieecnniifailc medical measurement of serum PFOS levels did not commence until the mid-1990's. [Note: Prior to this time.period, total organic fluorine was measured. Fluorine is 65%ofthe molecular weight of PFOS. The contri PFOS butionof PFOS was measured to in o 5 rganic fluorine, in Decatur employee pseprma,swaimlplltehserienfo1r9e79bebu0t.6a5naxly(tPicFaOlStevcahlnuiequinesppwemr)e.. 100 time consuming and required too large a volume of serum for routine medical surveillance.] es--------" 000011 * A voluntary medical surveillance program may not lend itself to an adequate characterization of tchoensdiesqtureinbucteioofnroefsepmopnldoeynete(if.luoSreolcehcetmioinc)albisase.ruBmecleavueslesifthpearetxitceinptaotfitohnirsatpeosteanrteiallobwiaass a was unknown for the fluorochemical medical surveillance programs at the Decatur and Antwerp e`mmapnluofyaecetusraitngthpelaDnetcs,ataurcr(osAsl-asbeactmiao)namlansutfuadcytwuarsindgessiitgen(eRdSGi)n.19T9h8etpourraponsdeoomflythseamsptuldey was to dVeotluenrtmairnyemwehdeitchaelrstuhrevediilsltarinbcuetpiornogorfaemmsplwoayseaerseearsuomnafbllueorreofclheecmtiiocnaolftlehveelsploabnsteprovpeudlaitniotnh.e A atontdalnoofn-2r3e2spDoencdaetnutrse(mnp=lo4y6e)eswewreerceormapnadroambllye swaimtphlreeds;pe1c8t6to(8ag0e%,)gpeanrdtiecripaantdede.mpRleospyomnednetnts adunrdat6i0onf.roOmftthhee frialnmdpolmalnty (swahmeprleedflpuaorrtoiccihpeamtiicnaglesmwpelroeyeneost,ma1n2u6fwacetruerefdr,omaltthheocuhgehmiincaolneplant aprnoadluyczteidoancrcuonrdainfglutoorotcheheemmipclaolyieseosc'cadseimoongarlalpyhuiscesd,).cuBrrleonotdorlelvoenlgseosft-thheeldfljuoobr,oacnhedmtihceals were llionceaatriofnasshoifojnowbsitwhityheianrsthweorckheemdicinalthpelacnth,emSiecarlumplPanFtO(S* l=ev0e.l1s1)w.erNeowpeoaskiltyivaesassoscoicaitaetdioinn awas observed between frequencyof self-reported hand-to-mouth usage or hand cleanliness and serum PFOS levels. Dra nil Assen Report PFOS 000042 `Table 4-2. PFOS Serum Concentrations: Occupational Populations 1007 3 50)" Tres onan | 1999 Production 1 = 1999 Management (n= 32) 0.04 Voluntary study. Estimated participation rates < 50%of employees who routinely or periodically worked in the chemical plant. * Random sample cross-sectional study. Voluntary cross-sectional study. The distribution previously repor of serum ted from PFOS levels the voluntary measured in this random sample was similar medical surveillance examinations. Thus, it to wa that s unlikely that employee serum PFOS levels higher than existed in these fluorochemical manufacturing that observed populations. in the medical surveillance programs Results from this random sample assessment are currently being used in retrospective cohort mortality studyof the the constructionof an Decatur employee exposure matrix population (see for the Section updated 4.4.3). `These biological monitoring data were also used in the ongoing analysis of health claims comparison analysis between chemical and film plant employees from 1993-1998 (see Section 4.4.3). There are many industrial uses of fluorochemical-containing compounds, and it is likely that PFOS could be found in serum samples from workers in these various user industries. 3M production employees are exposed to concentrated PFOS precursors whereas downstream wstoarrkteirngsmaarteergieanlesrailnlpyoelxypmoesredprtooduPcFtsO.SThpirsecsruugsgoersstsindcoownncsetntrreaatmiownoosrfkelresssshtohualnd 1h%avaeslroewseidrual serum levelsof PFOS than those observed in 3M production employees. The Sagamihara sampling data is consistent with this viewpoint. 4.2.3 Non-occupational Exposures In in 1998, three questions were addressedtodelineate the extent the blood of membersofthe general population not exposed to which PFOS occupationally might be present to precursor `molecules: cmimrrinsien . 1) 1s PFOS detectable in population known ot hu to man blood samples have worked in 3M ffrloumoraoccohrepmoircaatlem-abnausfeadc3tuMrienmgpolroyuesee plants? 2) IsPFOS detectable in pooled blood samples from the general population and from 000043 3) dIisfPfeFrOenSt dgeetoegcrtaapbhliecainl hliosctaotriiocanls ahcurmoassntbhleoUondistaemdpSlteastecsolalnedctoeudtspirdioertthoetUhneitientdrSotdautcetsi?on of POSF-based chemicals into the marketplace? sTuomamdadrriezssedthien Tfiarsbtltew4o-3.of PquFeOstSiocnosulsdevbeeradlestteucdtieedsiwnetrhee csoenrduumcotfeaddaunltdsthien dtahteaUnfirtoemdtShteamteasre m(lR)S2(7R,S3R1$)2.9,PRF$O3S0)coaunldd caolusoldbebededteetcetcetdedininthcehisledrreunmoufsaindgulatvseirnyBsemlagliluamm,otuhnetNoefthseerrluanmds(0,.1 aGsesromcaiantyi,onSswbeedtewneeanndPFJaOpSanan(dRSd2e7m,ogRrSa2p9h,icRSs2(8)..8.,Nagoe,inafnedregnecnedsecr)o,ultdimbeetdreevnedlsoapnedd sroeugracer(dsi)n.g Dre ia sss Repos PFOS 6 000034 Table 4-3. PFOS Serum Concentrations: Non-Occupational Populations (1998-1999) Tokyo (Japan): Head Office (n= 30) CInotmemregrenci(apoloLlaedb:oraaptporroixes5TM00 donors) Sigma (pooled: approx 200 donors) 35 Lots Commercial Labs US Blood Banks (n = 18 pooled samples)" European Blood Banks (pooled samples) Belgium (n= 5) Netherlands (n = 6) Germany (n = 6) `Sweden (n = 30 individuals) 28 individuals 11 individuals 0.044 0.033 0.035 0.030 0017 0.053 0.037 <0032 (LLOQ) 0048 003-0097 | 0.043 0.044 0.026 - 0.045 0.005-0.085 0.009- 0.056 0005-0.022 0039-0061 0,032:0.046 0.032-0.085 D6osnamoprlepsooplerinbflooromdatbiaonnk,,sutcoh 1a0s adgoen,orssepx,eorfsgaemopglrea.phGiecoaglrlaopchaitciaonl,lynodtisatvraiibluatbleed.acr3ostso the continental US and Alaska. Nota statistically valid sample of the US population (RS29). pooled samples, 10 donors per sample in Belgium and the Netherlands; 30 donors per sample in Germany (RS28). RST "Pilot analysis. Limited serum (0.1 ml) from children aged 6 or 12 who were enrolled in a group A streptococcal study. Study is in progress. RS31 TPoFOadSdrceosusldthbeetdheitrdecetxepdloinrastaomrpylqeusesotbitoani,nheidsptorriiocraltostahmeplmeasnuwfearcetuorbetoafinperdetcourlseoarrncwohmeptohuenrds (Ut.hSe. lmaitlei1t9a4r0y'rse)c.ruPitFsoOfSthweasKnoorteadentWecatrederian t(e1n94p8o-o1l9e5d1)s.amApnlaelsy(s1i0sodfon1o0rsSwpeedrissahmpslaem)plfersom csoalmlpelcetsedtianke1n9d5u8rriensgulttheedcionndaurcatngoefosfevvaerlaulepsofstr-o1m9n6o9ne-pdiedteecmtio1l0o2gipcpabl.stAudliiemsictoedndnuucmtbeedrinofthe UidneintteifdieSdt.ateAsnawleyrseisanoaflsyezreudmansdamspelreusmfProFmOStwloevCehlisnreasnegirnurgalfrpormovnionnc-edset(eLcintxtioan5,9 Sphpabndcoounlgd) be that were collected in 1984 and 1994 showed no detectable PFOS. Iitntarpopdeuacrtsiofnroofm PthFiOsS-lipmrietceudrssaomrpmloilnegctuhlaetsP;FthOeScopnrcelsuesnicoeninishhuimghalnysuenrceurmtacioninbceicdaeussweiotfhththee sparseness of the database. Definitive statements regarding time trends cannot be made at this time. Dr iAssertRor FOS 000015 n 4.2.4 Forthcoming Studies Several additional studies to address human exposure are being sponsored. These include the following: 1) CArnosasnailnysoirsdoefr t5o0o0btianidinviadcuraols,scsoenctteiomnpaolraarnaylyadsuilsotfbsleoordumsaPmpFlOeSs lfervoemlsthien aAdmuelrtsicbaynaRgee,d 2) `Agnenadnearlaynsdisionfauppptroox5iUm.aSt.egleyog2r5a0phiincdaivlidloucaaltieolndse;rly adult samples (ages 65 - 99) from an 3) Aonngoanianlgyssitsuodfy6of0c0ogcnhiitlidrveen'fsunscatmipolneasm(oagnegst2he- e1l2d)erflryomin2t3hestSaetaetstlweh, oWawsehriengentroonllaerdeai;na 4) `AgrcooumppAarsitsroenptoofcolcicvaelr tcolisniecraulmriPalFOinStrhaetimoisd-f1r9o9m0'3s0;human organ donors; and 5) MAartiymleantdrenind 1a9na7l4ysainsdof19f8l9uofrorcohmetmhiecaslasm,ein5c9luidnidnigviPdFuaOlSs,asinwseelrlaatsha1t2w0edriefcfoelrelnetctienddiivniduals in the two time periods (ages 20-60+). All of these research efforts are scheduled for completion by the first quarterof 2001 42.5 Indirect Exposure via the Environment `Human exposure via the environment is discussed as partofsection 3.1.1. 4.3 Effects on Human Health 43.1 ModeofAction, Toxicokinetics, Metabolism 43.1.1 Mode of Action Tsthuedimeescahraenciusrrmesntgloyveurnndienrgintvheestbiigoaltoigoinc.alSreevseproanlsessttuodPiFpOrSoviedxepocsluurees toobstehrevpeodteinntitaolximcooldoegsicoafl Ntoaxbicbietfy.eldCo1m9p8e8t)i,tcihoonlewsittehroflatstyyntahceisdissf(orHacuargrhearmpraontdei@nysbtienidni,ng19si9t2e)s a(Nnadbbbieofeenledrgeettailc1s9(9W8a,llace parnodliSftearraktoivo,n (1S9o9h8l)enhiauvsecbteael.n, s1t9u9d3i,edT.keIdnaaedtdialt.i,o1n9P87F).OSNhoascobnecelnusreipoonrsthedavteo bienednucreepacehreodxiosnome the importanceofanyof these possible mechanisms toxicity at this time. Dra ntl AssesmentReportPROS = 000046 43.1.2 Toxicokinetics and Metabolism Tsthuediaebdsomropsttioenx,tteinsssiuveeldiystirnirbauttsiobny, bpoottehntriaadliomleatbealboalnidsmdiraencdt eqxucanrteittiaotnioofn.PDOatSa hrealvaetibnegeonral droecsoevteoryseirs uamvaailnadblleivferrocmondciernetcrtaqtuiaonntsiotaftiPoFnO.S Ininadtdhieticoynn,osmeorlugmusPFmOoSnkceoyncdeunrtirnagtidoonssiinngraentidred 3M chemical workers have been followed in an attempt to estimate an elimination rate constant for the human. Absorption wPeFrOeSgiisvewnelalsaibnsgolerboerdalfdroosmetohfe4d.i2gemsgti/vkegs[ys"tCeJmP.FAOSrdadeimoolnasbterlastteuddythiant w>h9i5ch%aodfultthmeadloeseratwsas absorbed in the first 24 hours (RS60). aDpeprlmiaeld aubnsdoerrpotcicolnousfioPnFtOoSapapprpoexairmsattoelbye4p0os%sioblfetbhuetbiosdlyimsituerdf.aceInaroenaeosftmuadyl,ePaFnOdSfewmaasle New `ZoebatlaainneddWohnitdeayrsab1b,i7t,s a1t4,5a,0n0d028m.g/kAgnaalnydsilsefftoirntpotlaalceblfooord24flhuoourirdse(wRaSs54p)e.rfBolromoedd soanmdpalyesonweere and day 28 `male were samples from a single male and single 10.3 ppm for day one and 130 ppm for female. day 28. Total serum fluoride values for the The respective values for the female wdoesree,0i.t 9isplpimmitaenddi1n2t8haptptmh.e vAalltuehsoufgrhomthoisnlsytutdwyoianndiicmaatlesdwseormeemdeearsmuarleda,bsaonrdptoinolnyaftraomhitghhe day one and day 28 samples (O'Malley and Ebbens, 1981). NDuoequtaontthietaetxicveeptiinofnoarlmlaytiloonwisvaapvaoirlpabrleessounrethoefaPbFsOoSrp,tiionhnaolfatPiFonOeSxpforsoumreinwhoalualtdiobneeuxnploiskuerley.. If it does occur it would be associated with aerosols or particulates containing PFOS. Distribution pPoFtOenStidailsltyrsiebuvteersalprteidmoemsihniagnhtelrytthoanthseebrluomodcoanncednltirvaetri,ownist,hdelipveenrdcionngceonntrsapteicoiness being and dose. A r[a"dCioJlPaFbeOlSsdteumdoynisntrwahtiecdhtahdautltthmeaclaerbraotns-w1e4rien gliivveernaandsipnlglaesmiantrreapvreensoeunstsdo2s5eaondf34.%2omfg/tkhge d3o0s.e2,%roefsptehcetitvoetlayl,caafrtebron8-91d4ayvsi.a uDruirnienagntdhteh8e9m-edaaynpcousmtu-ldaotsievpeerfieocadl, etxhcerreattisoenxwcareste1d2.a6%m.eaAntof 8we9rdea:ysl,ivmeer,a2n0.t6i;sspuleacsomnac,en2t.r2;atkiiodnnoefy,to1t.a1l;claurnbg,on1-.11;4 sepxlpereens,s0e.d5;asanpdgb[oCnIePmFarOrSowe,qu0i.v5a.leLnotsw/egr concentrations (<0.5) were measured in adrenals, skin, testes, muscle, fat and eye. No radioactivity (<0.05) was detected in brain. (RS57). Scihgonliefsitcyarnatmeinnteer(ofhoeuprapteirccecinrtcbulyatwieoingohft PinOdiSeth)atsrebaetemnenrtepoofrrtaetds agsiveevnidseinncgeled ibnytrtahveefnaocutstdhaotses Of PFOS increased fecal elimination 9.5 times over control (RSS8). "The volumeofdistribution in male and female cynomolgus monkeys on daily dosing has been Dra ntl sessmentReportPOS 000047 " mesgt/ikmga/tdeadya)sd0e.m2onLs/tkrga(tReSd3a4)l.inMeaorn(k-esyqsuadroesded> b0y.9o9r)alinccarpesausleeiwnistehrPuFm OcSonc(e0.n0t2raatnidon2t.h0roughout tthhee ceuxmpuolsautrievpeerPiFoOdS(2d8odsaeysv)e.rsuTshesreeruwmasPFnoOSapcpoanrceennttsreatxidoinffceurrevnecseaapnpdeatrheedintdoibveidvuiarltusallolpyes of `idmegn/tkigc/aldafyorgrthoeupmo(nnk=e6y)swiansth5e.2t2w+o 0d.o7s4e pgrpomupsP.FOTSheinasveerraugmepselropmego/fktghecucmuurlvaetiivnetdhoes0e..0T2he two monkeys in the 2.0 serum per mgkg PFOS mcgu/muklga/tdiavyeddoossee.grAotupthheaednadnofavtehreag2e8-sdlaoypedoosfing5.4p0e+ri0o.d6,1speprummPFOS in Tcohnecseentdraattaisoungignestthea0v.o02luamnedof2.d0ismtgr/ikbgu/tidoanyogfr0o.u2psL/wkegrefoarpcpornotxiinmuaotueslydo3sipnpgmovaenrd a30t0woppormd.er of magnitude range. cIonnace2n6t-rwaetieokn cwaiptshulceu-mduolsaitnigvestduodsyeiwn acsynoobmsoelrvgeuds (mRoSn3k2e)y.s,Aat stihmeillaorwpearttdeorsneso,f0i.n0c3reaansdin0g.1s5erum p`mpgm/kgat/dtahye,esnedroufmthleevedlossiinncgrpeearsieodd,inrefsaiprelcytilvienleya.r fAatshtihoen0a.n7d5 rmega/ckhge/ddmoesae,nstohefi1n8crpeapsme ianndse8r5um aPcFcOuSmualpapteiaorneodftPoFsOatSuraitnet,hreesaecrhuimnoagf mmaelaenoafnd21f5empaplemmboyntkheeyesnadopfpetahreeddsoismiinlgarpeirnioaldl. dToshee `groups. Figure 4.1 shows the trend in group mean serum concentrations during the dosing period. Dr nid Assn Ror POS 000048 Figure 4-1. Mean serum PFOS concentrations for males and females during 182 days of oral dosing at either 0.03, 0.15 or 0.75 mg/kg/day. 350 300 E gam @Q a0 . o gE 3 i 10 2 50 ad a 503a 0 50 _ - {} - - ; 5a ao 100 Time (Days) E - 803 [ll 150 |oM0.03 mg/kg/d | AMO0.15mghkgid| oF 0.03 molkgld oF 0.15 mg/kg/d | AMO75 mgkgid | oF 0.75 mg/kgid 200 Male and female CR:CD rats continuously exposed to PFOS in the diet for 14 weeks (RS39) also showed a linear relationship between dose and serum concentration as is shown by the data in Table 4-4. Dra ilAssent Report PROS 000049 Table 4-4. Serum concentrations in male and female rats after 14-weeksof exposure to PFOS in the diet. --_-- Males Estimated Cumulative Dose Dose GroupTM 0.5 ppm 20 ppm (0.036 mgke) (0.1 mgkg) 5.0 ppm 20 ppm. (035 mgkg) (1.37 mgke) 32 126 311 233 (mSge/rkugm)PFOS 22pm T79ppm T 456 pm pm T T3 ppm m coa ncentration (8.5 1M) (59uM) Dose(OGLrAoWuMp") (3046 iM) Females 0.5 ppm 0.04 mg/kg) 20 ppm (0.16 mg) 5.0 ppm 20 ppm (041 mg/kg)' (1.6 mg/kg) Estimated 36 14.6 370 144.0 Cumulative Dose (mg/kg) Serum PFOS 6.7 ppm 269ppm 629 ppm 216 ppm coosncentration 33M)S(o 39pM) l (12601M) l (4329 uM) "Dietary concentration * Estimated dose based of on PFOS in ppm feed analysis, (ng PFOS/E dict) feed consumption and body weight during study D4i-s5tprriebsuetnitosn sacerrousms tchoencpelnatcreanttiaonasndfreoxmpoaspuhraeromfactohekifneettuiscinstuutdeyrochoansdubceteendddeumroinnsgtrparteegdn.anTcayble (orRaSl52g)a.vaDgeamfosr w4e2rdeatyrseaptreidorwtiothmavteihnigcl,edounrliyng(mcoanttironlg),an0.d1,du0r.4i,ng1.g6esotrat3i.o2n.mgS/ekrgu/mdawyasPFobOtSaibnyed ffertoalm ldiattmerss oprniogresttoamtiaotnindgayan21d. onThgeesptratei-omnatdianygsa7n,d1g4easntadti21o.n dSaeyr2u1mvwaalsueosbtaraeinreedprfersoemntpeodoilned the Table 4-5 Dra ntlssRs eportPFOS a 000050 Table 4-5. Maternal and fetal PFOS serum and liver PFOS concentrations associated with gestation (rats). Dose Group| Media Mgkgd" or Seum | 103126(16) | 4912123(7) 1051.01 (7) Liver - 23.443.76 (8) 9.17 1.08 (7) Serum |47.1500(16) |30317.0(6) 39.75.(950) Liver - 107252 (7) 42.519.4(6) 6 Serum |185% 14.0(16) 15886.6 (4) 1751452) Liver - 440 316 (5) 100+ 30.6 (2) 32 Serum | 36723.6 (16) 180 415 (6) 1912264(6) 2) Dams were Liver treated daily by oral - gavage for 42 598+ 83.9 days prior (o (6) mating, 265 +70 (6) during mating and through gestation. b) After 42 days dosing t`Thhee1a4p-pwaereenktdliaectkaoryfcsoturdryesapnodntdheencreepirnodtuhcetrieolnatsitoundsyhimpaoyfdboeseexptolasienreudmbyletvheel wfahcetnthcatomtphearing reproduction study was a gavage study, as opposed to the 14-week dietary study. In the latter wsteuidgyh,tmdgu/rkigngdtohseecloeuvreslesowfetrheeessttuidmya.teFdebeadsecdonosnumfpeetdioannailsysains,erfreoerd-cproonnseummpetasiuorneamnedntb,oddyue to the possibiltyof spilled (unconsumed) feed. Dietary doses also represent a continuous source of exposure as opposed to pulse dosing by gavage. Serum levels at the endoflactation after exposure in the PFOS reproduction study are represented in Table 4-6. Table 4-6. Comparison of serum PFOS levels at the end of lactation after dosing rats with PFOS for 42 days pre-mating, during mating, gestation and through lactation (approximately 13 weeks). 5352035 There is conclusive evidence from the cross-fostering study that PFOS distributes to milk and also crosses the placenta. These data are discussed in Section 4.3.4. refnittsssmenRepo FOS 000051 Metabolism PFOS is not known to undergo further metabolism or to form conjugates. Preliminary data from aSnuaglgyessitsotfhautriPnFeO,Sfeicsensoatnmdettaisbsouleiszoefdra(tJsohansswoenlletaasl,th1e98i4n)h.ereAnntalstyasbiislibtyyofLpCer/fMlSuoofrisnearteudmaannidons liver samples from recent studies has not revealed any evidence of metabolism CmeerttaabionlcihsemmitocaPlFsOmSa.deFofrreoxmapmeprlfel,uoNr-oEocttFaOneSsEulcfaonnyblefmleutoarbidoeli(zPeOdStFo)PmFaOyS.unIdnerognoe astduedgy,reienof which rats were administered "C-N-EtFOSE in feed, at least 28%of the radioactivity found in the liver at 48 hours was PFOS (RSG). This represented 4.4% of the administered dose. Excretion Single intravenous doses (mean 4.2 mg/kg) of ["CJPFOS in 0.9% NaCl were administered to male rats the urine (RSS7). By 89 and 12.6% had days been after dosing, 30.2%of the administered "C had been excreted in the feces. Whole body elimination in the excreted male rat in laipfpeeoafre"dCotofb7e.5bidpahayssicf.ollInoiwtiianlgrseidnigslteriobruatlioandmfirnoimsttrhaetipolnaosfma["yiCeIlPdFedOSa p(lmaesamnadeolismeina4.2timogn/khagl)f- dtoosmealtehrroautgsh(RuSr6i0ne).anIdnftehceesafaoftreerme8n9tdiaoynsedinidnitcraatveesntohuaststthuedyh,alef-lliimfienoafteiloinmoifnoantlioyn42f.r8om%tohfe the body is > 89 days in the male rat. Cynomolgous monkeys have been followed for one year in recovery after six monthsofdaily loriamlitdeods(itnwgobpyecraspesxulpeeratd0os1e5gorro0u.p7),5tmhge/vkagl/udeasysu(gRgSe3s2t).meWahnilseertuhme neluimmbienratsioofn ahnalifm-allisveasroef a1r8e9ldiakeylsyfnoor ttrhueemdiidf-fdeorsenecersecionvseeryrugmroPuFpOaSndel1i7m5indaatyiosnfroarttehsebheitgwhe-ednosteheremciodv-edroysgeraounpd.hiTghhe-re dose groups. A low-dose recovery group was not part of the study design. cFehcoallesatnydratmotianlee(x~cr2e.t7igo/nkogf/d)**iCnwteheriermdaiertkefdolllyowiinncrgesaisnegdleinimntarlaevernatosusaddmoisneisstoefre[dCIPFOS e(nJtoehrnoshoenpaatnidc Gciirbcsuolna,ti1on9o8f4 aPnFdOSR.SS8C)h.olTeshteryersaumlitnsesaudgmgiensitsttehratedthaetr4e %wabsyswiegniigfhitcainntfeed to male rats decreased the retentionof carbon-14 in liver, plasma, and red blood cells and increased tdhoeseedliimnitnraatvieonnooufslcyarwbiotnh-P14FOvSia-"feCce(smaefatenrdiovsed,os3i.n4gmwgi/tkhg)P.FORSa-t"s"Cw.erGersoaucprisfiocfedfiavte2r1atdsawyesre peoxsctredtoisoen.ofTh"eCmfeoranchloilveesr,typrlaamsimnae,-tarnedatreeddrbaltsoowderceellcocmonpcaernetdrattoiomneaasnwceolnltraoslfreactalvaalnudesu.riMnearayn cbhlooloedstceylrlasmi(0n.e3-tirge/aet)edrerpatre"sCentcoancdeenctrreaatsieonfsroimn lmievearn(c9o.n4turgo/lg)r,atplcoanscmeant(r0a.t9iuogn/smlo)f,3a.8n,d7r.e7d, and 6.0 9.5 fold, fold. rTehspeecetxitveenlyt.ofuFreicanlareyli"mCinaetliimoinn(at7i5o.n9,%aswiatrhecsuhlotleosfttyhrearmeilnaetitvreelaythmeingth)rwataesoifnfcerceaalsed elimination of "C was lower in cholestyramine-treated rats. The extentoftotal elimination of HC (urine plus feces) was higher in the cholestyramine-treated rats. Dr tidsss Report FOS " 000052 Human Data Serum PFOS levels in three retired male 3M chemical workers followed for five and one-half years suggested a mean serum climination half-life of 1,428 days. A recent initial analysis of 27 3M fluorochemical production workers retirees" sera, collected three timesover a 12-month period, has suggested that the serum elimination half-life of PFOS in the human may be much lower, approximately 300 days [RS53]. The rangeofthe initial serum PFOS levels in these retirees was from 0.2 to 4.6 ppm. These retirees have their serum collected and analyzed every six months. More definitive serum PFOS half-life estimates are expected within the next year upon collectionoftwo more samples. Summary The data provide no evidence for PFOS metabolism in any species. PFOS is readily absorbed after oral exposure but absorption by the dermal route is low. There is evidence that absorbed PFOS is bound to protein and distributed primarily in blood and liver. PFOS undergoes entrohepatic recirculation. There is slow whole body elimination in both sexes. At lower and moderate doses, body-burden is proportional to cumulative dose. In rat studies it is clear that PFOS can traverse the placenta and expose the fetus in utero. PFOS is also distributed in to the milkof lactating females. 43.2 Acute Toxicity Studies Numerous reportsofacute studiesofPFOS have been performed. Data from an inhalation study in rats, two oral studies of rats, one dermal studyofrabbits and one dermal and eye irritation studyofrabbits are noted below. Inhalation Exposure tInhae psottuadsysitoumdestaletromifnPeFtOheSmaesddiuasnt lientahiarl tcoonScpernatgrautei-oDna(wlLeCy),ratRsuastclheveetlasl.of(119.7899)t0ad4m5i.n9i7stmegr/eld PFOS. An LCy of 5.2 mg/l was estimated from this study (RS2). The rats in all groups showed signsof toxicity including emaciation, red material around the nose or other nasal discharge, yellow material around the anogenital region, dry rales or other breathing disturbances, and general poor condition. Abnormal in-life observations were reported to be less frequent in the lower exposure groups. ADtisnceoclorroaptsiyo,notfhethmoestlucngomwmasonalasbonoobrsmearlvietdy iwnacsondtirsoclolroarattaionndotfhetrheefolriveemr aayndnloutngb.e treatment related. The most significant treatment related abnormality was discolorationof the liver. Among animals that died prematurely, decreased body weight, discolorationof the lung, and discoloration and distention of the small intestine were also observed. oral `The studyofDean et al 1978 determined an acute oral LD, and 95% confidence limits of Dre tnscsi Report PFOS - 000053 251 (199-318) mg/kg. The study report by Gabriel 1978, tested only two doses and determined the acute oral LD, was greater than 50 mg/kg and less than 1500 mg/kg (RS3). Dermal Exposure Nfeomasliegnailfibciannotrtaobxbiictistywewraesdoobsseedrvdeedrmianlaly19u7n9depreroccucltuasnieoonuswiatbhsoSr0p0ti0omngs/tkudgyPiFnOwShifcohr m2a4lheouarnsd and observed for 28-days post-dose (RS54) 4.3.3 Repeated Dose Toxicity 4.33.1 PROS PstFuOdySihnarshbeesuesn mstoundkieeydsin(9R0S-3d5a,yRsSu3b6c)h,roannidcidnieat2ar6y-wsteuedkieosrailn(rcaatsps(uRlSe3)7s)t,udiny ain9c0ydnaoymoglagvuagse monkeys (RS32). A two-year chronic feeding study in ratsis currently in final stages of completion (RS39) Tchhreonsitcudsiteusdiynirnherastussamnodntkheey2s6a-nwdeetkhes9tu0d-ydaiyn rcaytnsotmuodlygwuesrmeornekpoerytsedweinre19a7l8s.o dTehseigmnoerdetorecent ppraotvtiedmeofsetrouximcdaetfaf.ectTshoebscaerrlvieerdsitnutdiheossearsetusduimesmairs iszimeidlairntToatbhlaet 4s-c7e,nainndtihtecmaonrbeersecceenntthsattudtihees. Tdohseeoslhdeorwsetdudcioenssiisntcelnucdyeodfmtouxcihcheifgfheectrsd.osIensthoenfbooltlhowriantgs,atnhdeprreicmeanttess.tudAireesaasreofdeosvcerrilbaepdoinn detail IrnectehieverdecPenOt S26-bwyeceakpscuylneoamtodlogsoeussosft0u,dy0,.0g3r,o0u.p1s5,ofansidx0m.o75nkmegy/skogf/edaaych(RsSe3x2)(.4/sTewx oatalnoiwmadlosse) pweerresefxolflroowmedthfeorcoanttrloela,st05.215waenedks0.f7o5llmogw/ikngg/tdhaeylgasrtouadpmsiwniesrteraatsisoingnoefdPtFoOaS.recAotvetrhye gernoduopfatnhde dosing period, high-dose females showed reduced body weights compared to controls, but the differences were no longer obvious by the endofthe recovery period. Tdiweod amfatleresdofsrionmg tohne D0.a7y5 1m5g5/k(gW/edeaky 2g3r).ouCplidniidcnalotsisgunrsvinvoetetod tihnetshicsheadnuilmeadl sianccrilfuidcee.d cOonnestraincitmeadl pupils, pale gums, few, mucoid, liquid and black-colored feces, low food consumption, hypoactivity, labored respiration, dehydration, and recumbent position. In addition, the animal wdeatsercomlidnetdo ttohebetopucuhl.moAnnareynlnaercgreodsilsivweirtwhassevdeerteecatceudtebyinpfallapmamtaitoino.nC.auOsneodfayde1a7t9h, wthaessecond male was sacrificed in a consumption, excessive moribund salivation, condition. Clinical signs noted included low labored respiration, hypoactivity and ataxia. food Cause of death `was not determined. Mfeamlaelsesanidn tfheema0l.e1s5 ianndth0e.07.575mgm/gk/gk/gd/adyaygrdoouspes-garpopueparheaddtloohwaevretoltoawlecrhohliegshtedreonlsiatnydlmiapolpersotaenidn cdhaoylses1t5e3roalnddur1i8n2g, tarnedatnmoenptr.esHtDudLy cvhaollueesstearroelavvaaliuleasb,lehofworevceormp,awreisroeno.nlTyhedeetfefrecmtinoendtootnalstudy crhfolensitaersoslswnaesnrReevpoerrtsFeOdSwithin 5 weeks of recovery and high density lipoprotein cholesterol a" 000054 increased within 9 weeksofrecovery. Trilodothyronine values were lower in males in the 0.75 `mg/kg/day dose group on day 182. However, total thyroxine and thyroid stimulating hormone levels were normal and thyroid gland showed normal histology. Perhaps related to the observed decrease in cholesterol at the 0.75 mg/kg dose was a progressive decrease in estradiol in males. At terminal sacrifice, females in the 0.75 mg/kg/day dose-group had increased absolute liver weight, liver-to-body weight percentages, and liver-to-brain weight ratios. In males, liver-to body weight percentages were increased in the high-dose group compared to the controls. "Mottled" livers were observed in two high-dose males and in one high-dose female. Ofthe two males not surviving until the scheduled terminal sacrifice, one had a "mottled" and large liver. Three of 4 high-dose males (including those that did not survive to scheduled sacrifice) had centrilobular or diffuse hepatocellular hypertrophy which was also observed in all high-dose females. Centrilobular or diffuse hepatocellular vacuolation occurred in 2 of4 females and 2 of4 males in the high-dose group. No PFOS related lesions were observed either macroscopically or microscopically at recovery sacrifice indicating that the effects seen at terminal sacrifice were reversible, The LOAEL for this study is 0.75 mg/kg/day based upon death, liver effects, and effects on cholesterol. The NOAEL is 0.15 mg/kg/day. All effects appeared to be reversible. Interim results at weeks 14 and 53 are available from the ongoing chronic rat study (RS39). That sPtFuOdySiantv0o,lv0e.5s,g2r.o0u,p5s.o0f,6a0ndo2r0.700 pCprml.:CTDhr(oSuDg)h IwGeSekBR53,rahtisogfhedaocseh fseemxafleedsdsihetoswceodntraeidnuicnegd body weight gain and reduced food consumption. Reduced serum cholesterol and increased serum alanine aminotransferase (males only) was seen in high-dose animals. Mildly increased urea nitrogen was seen in animals fed 5 or 20 ppm, and serum glucose was reduced in high dose males and females, and in males at 2 and 5 ppm at week 53. At the 53-week sacrifice, high-dose rats showed increased absolute (males only) and relative liver weight. Centrilobular hepatocyte hypertrophy and midzonal to centrilobular vacuolation was increased in incidence in males at 20 ppm, and high-dose females showed an increased incidenceof centrilobular hepatocyte hypertrophy and pigment. Data on serum PFOS levels are available from the 26-week cynomolgus monkey study and for week 14 of the chronic rat study. The relationships between PFOS serum levels and toxic responses for these two studies are presented in Table 4-8. The serum levels presented in Table 4-8 represent preliminary analyses availableasof July, 2000. These values wil change in the final analytical reports based on adjustments for purityof the samples and other possible: corrections. ---- a 000055 Species Table. SummaryCloifnRiecpaleaOtb-sDerovsaetSitoundsi;esClfionricPaFlOPSa.thology; Gross Pathology; g2 Study 0-Day Dictary | (Strain) Rat | Dose units) Opp) |[SM/n_S| F Histopathology (M = Male F = Female) [w Noam ~g () 30 (Goldenthat et al. 19788) 10 SM/SE SM/SF [nL Sbloutdaymawtee-oxialgaTcpheltattsem,tarangslaumtianmsaet,elipvyerrudviastceoltorraantsiaomninase, Tplasma [3deaths; sensittioevxtietmayl stimuli,redmataerounrdthieeayeslor a`mlokuathl,in4efopohdoscphatoase,nT bsloodpulgalusmcmoascer,peaTtbitlnoiondeipuhroesoaphonkina,se, cnoiutnrtog(eFn),, helmeougkloocybtien,counhte,maitvoecrreitn,laregreytmhnr,onceycterocsoiusn&, reticulocyte eu SMSF | 1 Dheepaat;oceelmlaucliaartihoynp,erctornovpuhlys,iosntso,msatcohmdacih smuccoosallho&yprhereakmeotrraitrohsoaigsne, bone. `marrow hypoceluiariy, thymic follicular atrophy, splenic lymphoid sTomlallcuilnatresattirnoepsh,ys,ketlreotpalhymoufscmleeseantterric&olydpmeprhhmaynlodaecsa,ntahotsirs,oopfhilyiin 1000 SM/SF | hDyepaetrhk;ehruantocshiesdposture Tek Tar 3000 opm) SM/SF |e Death;hyposcivity OMII0F | Noell Dietary (DSapwrlaegyu)e | 05 [2 (Part ofongoing 5 1100MM//1100FF ||= NNooeeffffecctt 10M/10F |= Hepatocellular hypatrophylandvacuolizaton in M at 5 pom P27sotudny, i 2 10M/10F [a li4vbeordcyweeig1lhptla,lmscihtoo,lyelstCeorAolo(xMi)d,asTleiavcetirviwteyight,enlarged & vacuolated Dot mr 105 re St So say |aesmue || AowTteane. Su|_|mmaryiotfoRpmaeotpoogsyDnots=slitocirPniOFSFaennos Gros abs | | Monkey [10 (Goldenthal et Si Ciaraone 0 eSyi.doconssdois, vnecr, sn, cogs, ene 100 Ceoianbi doarbs.vorse san. mb om 3 SoG [RT [INTE [7 Nemailemnacmeesduees. rone pton cnge rhe Monkey 05 (Goldenthal et 15 + Di eeyatTaw tio sily oocytd df,rtrceoslcyosnl1 & a. 1978) id 2M/2F 2IM/2F |w Deathwithin 11 - 20 days; 4bodyweight, markedweakness,anorexia, L activity, emesis, diarrhea, tremors,prostration,congestion, hemorrhage | Deathwithin 7 - 10 days; body weight, marked weakness, anorexia, 2M/2F | Deathwithin 3 - 5days; +bodyweight, markedweakness,anorexia, 2MI2F |y Deathwithin 2 - 4days; 4body weight, markedweakness, anorexia, 2M/2F |w No Adverse Effect; Sl&iintg ermih ttentt activityin 3of 4animals 2M/2F | 4 Blo&moucdusin tools, diarhea, dehydration,tremors, J body weight, 2MI2F 4cholesterol, mar4kacteividty dehydration, rigidity, convulsions, prostration, 4 serum cholesterol, alkaline phosphatase, T SGOT erm 000057 WeSctkudy Capsule (Thomford 2000) Species Table dT. Summary`oCflinRiecpaleaOtb-sDerovsaetSitoundsi;eCslfionricPaFlOPSathology; Gross Pathology; |Cy(nSotrmaoilng)y||0(Dmogsek(gudniatys))||6M76wnF _| |H=istNoopcaltlhooeltogy (M = Males F = Female) shonkey | 003 SM/AF [a Noeffet 015 6M/6F |a Noadverseeffect 07s GM/GF |w 2deaths; bodyweight, foodconsumption,black & mucoidstools, activity, dehydration, labored respiration, cholestrol, L HDL cholesterol, riodathyronine (normalT4 &TSHest)radi,ol liver discoloration, 1liverweight, vacuolatedlivercells Ort mee105. | | 000058 0 | Table 4.8 PFOS Toxicity Data for Mammals: Key Observed Effects, Serum and Liver PFOS Concentrations, and Cumulative Dose Group' Shaerct Serum PFOS Liver PFOS. |Cumulative (ppm) . Concentration Concentratio (ppm) Dose (mg/kg) [OGmgigd [NOEL 8 |3 [ sa | enlargement females 0.75 mgkg/d 0.75 mg/kg/d males Decreased T3 (normal T4| > 152+30 | 415 (average) 7.7 [F ome erese ]IZT EI0 [ldl leImo17] Death or carly sacrifice for| > 150, <300| 415 (average)| > 100, <137 14-Week InterimofChronic Dietary Study in Sprague DawleyRats (Covance 1999a) ee [[0250ppppmmFMeamlaelses[[NNOOEELL 5.0 ppm Males | Hepatocellular vacuolization || 616755 || 7isss ||_~=137 || 386.53 244 20 ppm Males Hepatocellular 134 hypertrophy and vacuolization; decreased cholesterol; increased AAT hvyapceurotlraotpihoynand | 599.94 106 { | Orot tnietssmse:RpeaprPFEOOS SApepec 000059 * 433.2 N-EtFOSE N-E(FOSE has been studied in ninety-day studies in rats (RS49) and rhesus monkeys (RS50). A two-year chronic toxicity study was completed in 1987. That study used a "wide range" material that included many short-chain fluorochemicals and was not representative of the typical material currently used in commercial products, A robust summaryofthis study is included (RS33). Subsequently, a two-year chronic study in rats using a more representative "narrow-range" product was initiated and is currently in progress (RSS1). The patteroftoxic effects seen in these studies is similar to those seen with PFOS. The primary target is the liver, with doserelated increases in liver weight and macroscopic and microscopic liver lesions in rats. In the 90-day rat study, N-EtFOSE was fed in the diet at levelsof0, 30, 100, 300, 1,000, 3,000 and 10,000 ppm to groupsoffive Charles River CD ratsofeach sex (RS49). All rats at the 1,000-, 3,000- and 10,000-ppm dosage levels died between days 9 and 29 of the study. Findings in high dose animalswere consistent with those found in animals exposed to high doses Of PFOS. These included compound-related gross and microscopic liver lesions with consistent changes in biochemical parameters. N-EFOSE was administered to groupsof two male and two female rhesus monkeys by gavage at dosage levels of 1, 3, 10 or 30 mg/kg/day (RS50). A control group received the vehicle, propylene glycol. On and after the second dayof study, all the monkeys, including the control `group showed anorexia, slight to marked decrease in activity and ataxia. The ataxia disappeared from all the monkeys directly after the amountof propylene glycol used was reduced from 5 to 2 ml/kgon study day 3. Most of the monkeys, including those in the control group lost body weight carly in the study. At 12 weeksofstudy all the monkeys were at or near the original body weight except for the groups receiving 10 and 30 mg/kg/day. At the endof the study the differences in the mean body weights of the treated and control groups were not statistically significant. Microscopically, the adrenals from one male and two female rhesus monkeys at the 30 mg/kg/day dosage level had compound-related slight to severe lipid depletion, and the pancreas from the two female monkeys at the 30 mg/kg/day dosage level had compound-related moderate atrophyof exocrine cells. No liver lesions were seen, however. In the ongoing two-year bioassay using a test material that is more representative ofmost material currently used in commercial products, groupsof60 or 70 Crl:CD(SD)IGS BR rats of cach sex were fed diets containing 0, 1, 3 30, 100, and 300 ppm N-E(FOSE (RS51). Due to excessive toxicity (reduced body weight, reduced food consumption) the 300 ppm group was terminated at about week 8 and the 1 ppm and additional concurrent control group were added. Atsacrifice, the 300 ppm animals showed hematologic changes (reduced red blood cell count, hematocrit, and hemoglobin), clinical chemistry changes (lower glucose, globulin, and cholesterol, and higher BUN, albumin, total bilirubin (males only) aspartate aminotransferase (males only) and alanine aminotransferase), liver enlargement, and hepatocellular hypertrophy and necrosis, and hemorrhage in the liver. A similar (though less severe) pattemofeffects was seen at the 30 and100 ppm groups at interim sacrifices at later measurement times. This pattern included: reduced body weight gain over the first 53 weeks; mildly decreased red blood cell count, hemoglobin, and hematocrit for females in the 100 ppm dose group; mildly lower glucose and mildly higher urea nitrogen for Tr -- El 000050 animals given 100 ppm (predominantly at Weeks 14 and 27; moderately higher albumin and moderately lower globulin (predominantly at Weeks 27 and 53) in 100 ppm males. Hepatocellular hypertrophy and vacuolation were observed in 100 ppm animals at week 53, and hepatocellular hypertrophy was also seen at week 14 in males given 30. Decreases in body weight and total serum cholesterol were prominent effects in this study. Male body weights for the 30 ppm and 100 ppm dose groups were significantly lower than control values through week 53ofthe study. Females also experienced lower body weights. In the 3 ppm dose group females, transient but significantly lower body weights occurred on weeks 14, 15 and 16. Females in the 30 ppm dose group also had significantly lower body weights through week 29 and again on week 37 and weeks 43-53. The 100 ppm dose group females had significantly reduced body weight through week 53. Cholesterol was significantly lower in males in the 3 ppm, 30 ppm and 100 ppm dose groups at week 14. This effect was present at weeks 27 and 53 in males in the 30 and 100 ppm dose `groups. In contrast, females in the 30 and 100 ppm dose groups had significantly lower cholesterol only on week 14. 433.3 N-MeFOSE N-MeFOSE has been studied in a 13-Week dietary study in Crl:CD (SD) IGS BR rats at doses 0f3, 30, and 100 ppm (20/sex/dose) (RS38). The only effect seen at 3 ppm was a slightly reduced body weight gain. Effects seen at 30 ppm were: lower serum globulin, cholesterol and triglycerides in males; lower terminal body weight in males; increased liver-to-body weight ratio in males and females; increased absolute liver weight in females; increased incidenceofcentrilobular hepatocellular hypertrophy in males and females, and a slight increase in minimal hepatocellular vacuolation in males. At 100 ppm, the same effects as at 30 ppm were seen (but at higher incidence andor greater severity), plus lower serum cholesterol and triglycerides in females; lower hematocrit and higher BUN in both sexes; higher serum albumin in males; higher serum AAT in males increases in all liver weight parameters in both sexes (relative and absolute); liver coagulative necrosis, hepatocellular pigment, and erosion of small portionsof stomach mucosa in both sexes (RS38). 433.4 Summary PFOS, N-E(FOSE, and N-MeFOSE produce similar toxic effects in subchronic studies in rats and monkeys. The effects occurring at the lowest doses are liver cell hypertrophy, in some cases with vacuolation, a decline in weight gain, and areduction in serum cholesterol levels. The most recent data, summarized in Table 4-9, provides dose-response information on these effects. The fact that the three compounds produce similar effects suggests that these effects may be due to the presenceofPFOS and not the precursor compounds. This suggestive evidence can not be confirmed until all of the serum data have been collected and evaluated. Results from the chronic studies of PFOS and N-EtFOSE will become available in the future. CL -- 5 000061 Table 4-9 Comparative Effects Among Three Perfluorooctanesulfonyl Fluoride-Based Chemicals Effect Dose at which effect occurs ater 14 weeksof dietary compound administration in rats. Hepatocellular enlargement Cholesterol lowering Body weight [elonnerimgiese | 00popmoonnets | pom fms 20ppmm ootnees Liver to Body, |3N0 EppWmOmaSlesE, " [ 3N0-pMpemFmaOleSs,E' | S pPpmRmOalSes | 100 ppm females _| 100 ppm females _| 20 ppm females 3 ppm males 30 ppm males 20 ppm males 30 ppm females | 100 ppm females | -- ND females* 30 ppm males 30 ppm males 20 ppm males 100ppm males 30 ppm males 20 ppm males * ND, not detected. * N-Ethyl-perfluorooctanesulfonamido ethanol * N-Methyl-perfluorooctanesulfonamido ethanol Perfluorooctane sulfonate Slight but statistically significant effect occurring only at the terminal weighing 4.3.4 Reproductive and Developmental Toxicity Developmental toxicity studies in rats and rabbits and 2-generation studies in rats for PFOS and N-EFOSE were reviewed. The N-EWFOSE studies are included for comparative purposes since, as noted above (Section 4.3.1) tis believed to be readily metabolized to PFOS. In addition, the results ofa PFO cross-fostering study are presented and discussed. All studies employed the oral (gavage) route for administering the chemicals. Developmental Studies Separate studies with PFOS and N-EFOSE assessed the effectsofpregnant rat exposure on prenatal developmentoftheir embryos and fetuses. Each chemical caused maternal and fetal toxicity and in the case of N-E{FOSE, a low litter incidenceofanatomical malformations were seen at very high doses. Initial studies with both chemicals reported a lesion in the lensof the eye in all treated groups (RS41, R45). The causal association between this effect and chemical exposure. was subsequently retracted by the study director when it was established that the "lesion was an artifact associated with the method of free hand sectioning used in the fetal examination. These lesions were not observed in repeat studies in this laboratory. Additional prenatal developmental toxicity studies with PFOS and N-E(FOSE have been performed in the rat and rabbit. Key aspectsofall studies are summarized in Tables 4-10 and 4-11. CS -- se 000052 Table 4-10. Oral (gavage) PROS Developmental Toxicity Studies Design NOAEL LOAELTM Effects Reference Rat SD Mat. 5 Mat. 10, Mat Body RS45 Group size: 22 Dev.10 Dev.None weight. Dose:* 0,1,5,10 Rat SD Mat. 1 Mat. 5 Mat. Body wt. RS46 Groupsize:25 Dev.| Dev.$ Clinical signs, Dose:* 0,1, 5,10 gi. lesions. Dev. Body wt, vise. anom., skel. var. Rabbit NZW Mat. 0.1 Mat. 1 Mat. Body wt. RS44 Group size: 22 Dev. | Dev.25 Abortions Dose:*0,0.1, 1,25, Dev. Bodywt. 375 Delayed ossification * (mg/kg). Rats dosed on GD 6-15. Rabbits dosed on GD 7-20. Results from the PFOS studies were similar. Matemal toxicity and developmental toxicity was consistently seen and expressed as reductions in matemal weight gain or fetal body weight Reductions in food consumption commonly paralleled the effect on maternal weight. Fetal effects were primarily associated with maturational delays, e.g., Skeletal variations and delayed ossification. Abortions were observed in rabbits at a dose of 2.5 mg/kg and higher. The lowest developmental toxicity NOAEL for rat and rabbit are the same, | mg/kg body weight. The matemal toxicity NOAEL was 0.1 and 1.0 mg/kg for rabbit and rat, respectively. -- ss 000063 Table 4-11. Oral (gavage) N-EFOSE Developmental Toxicity Studies Design NOAELY LOAEL* Effects Rat SD Matemal 25 Matemal 37.5 Mat, Body wt, deaths Group size: 22 Develop.25 Develop. 37.5 at75 Dose:* 0,25,37.5,75 Dev. Body wi, cleft palate, stemebrac mal. Rat SD Matemal S ~~ Matemal 10 Group size: 25 Develop. 5 Develop. 10 Dose:* 0,1,5, 10,20 Mat. Body wt. Dev. Body wi, delayed ossification Reference RS4T RS42 Rabbit NZW Maternal 5 Matemal 15 Mat. Body wt. RSSS Group size: 18 Develop.5 ~~ Develop.15 Dev. Fetal & Dose:*0,1,5.15 Neonatal Viability, resorptions. Rabbit NZW Matemal 0.1 Matemal | Mat Body wt. RS40 Groupsize:22 Develop. 1 ~~ Develop.25 abortions Dose:* 0,0.1, 1,25, Dev.Late resorptions. 375 * (mg/kg). Rats dosed on GD 6-15. Rabbits dosed on GD 6-18 or 7-20. `The more recent rat study with N-E{FOSE (RS42) showed maternal and developmental toxicity expressed as effects on body weight, this is similar to thatofthe earlier study (RS41). Concordance is not good between the 2 rat studies as to the NOAEL or LOAEL doses. Morphological defects in fetuses were seen only at doses of 37.5 mg/kg and higher. The results of the rabbit studies (RS40, RSS) are similar as to the nature of the effects but there are: differences as to doses that caused matemal toxicity. Fetal survival during the 24 hour incubation period was significantly lower at the 15 mg/kg dose (RSS5). The rabbit and the rat study conducted at similar and slightly higher dose levels indicate that the primary early maternal effect is associated with depressed body weight. The lowest NOAELs occurred in the rabbit study; 0.1 and 1.0 mg/kg for matemal and developmental endpoints, respectively. `When resultsof the PFOS and N-EFOSE developmental studies are compared, the type of effects, and doses that cause those effects, are similar. Fetal toxicity, as conirasted to anatomical malformations, characterizes the principal effectofboth PFOS and N-E(FOSE. Matemal toxicity also occurs at doses associated with developmental toxicity. Rabbits exposed to N-EtFOSE have a tendency to abort liters or resorb fetuses. These effects are possibly causally linked to the maternal effect. This typeofresponse was not prominent in rats exposed to cither PFOS or NEtFOSE. ref ttlAssen Reon FOS ppenic 56 000064 Two-Generation Studies Reproductive parameters generally were not affected by PFOS exposure in either generation of either sex in a 2-generation study in the rat (RS47). The exception was adecrease in implantations and liter size in F, females at 3.2 mg/kg, the highest dose tested. The carly adverse response in adults and in pups is reduced body weight gain in both sexes. Most significant was the death of all F, pups in the perinatal period at the matemal doseof 3.2 mg/kg bw/day. Mortality was also seen in F, pups from dams that received 1.6 mg/kg. The dose-response for this 9ef8f.e3c,t6i6s.1staeenpda0s.d0e%mofnosrttrhaet0e,d0b.1y,v0i.a4b,il1i.t6yainnddi3c.e2s m(sgu/rkvigvadlosfer,ormesbpierctthivteolyL.DS4e)veorfi9t8y.o7f,e9f8f.e3c,t on F, pups in the lactation phaseof the study resulted in post weaning dose groups being reduced to 0,0.1'and 0.4 mg/kg. These 3 dose groups proceeded through amating, pregnancy and postnatal evaluation phase until F, pups were 21 days of age. The F, rats in all these groups developed normally as measured by an array of developmental milestones, including neurobehavioral performance. Effects on reproduction, lactation and on postnatal viabilityofthe F; pups were modest and transient. The NOAELS from the study and the effect(s) seen at the next higher dose are: F, generation - 0.1 mg/kg; at the 0.4 mg/kg dose effects on body weight gain size - 1.6 mg/kg; for reproductive effects at 3.2 mg/kg reduced implantions and litter F, generation -- 0.4 mg/kg; at the 1.6 mg/kg dose pup mortality and decreased body weight - 0.4 mg/kg for reproductive effects, the highest dose tested F generation -- 0.4 mg/kg, the highest dose tested `The N-EFOSE 2-generation study (RS43) wasof a design similar to the PFOS study and gceonnedruacttieodn iinn tthhee sNa-mEetFlaObSorEatsotruyd.yAcodmesmiegnncdeidff2er8edncaeyswaprsiotrhattodcooshianbgiotfatitohneofpatrhenetaslex(eFs,)as contrasted to 42 days in the PFOS study. The doses were 0, 1,5, 10, 15 mg/kg/day. There was a decrease in F, litter size and pup viability in the 10 and 15 mg/kg dose groups during the perinatal period. The dose-responsefor this effect was steep as seen in viability indices (survival from birth to LD 4)of92.8, 99.1, 92.0, 30.2 and 1.20% for the 0, 1,5, 10 and 15 mg/kg dose, respectively. The last 2 pups in the high dose group died on LD 5 and an additional 6 of 60 pups alive onLD 4 in the 10 mg/kg group died between LD and 14. Due to the severe effects seen in F, pups at the two higher doses, post weaning portionsof the study were reduced to 0, 1, and 5 mg/kg groups These dose groups proceeded through a mating, pregnancy and postnatal evaluation phase until F, pups were 21 days ofage. F, rats in the 0, 1, and 5 mg/kg groups developed normally in the post weaning period as measured by an array of developmental milestones, including neurobehavioral performance. Effects on F, reproduction and lactation and on post natal viability of the F, pups were seen at the 5 mg/kg dose. The NOAELS from the study and the effect(s) seen at the next highest dose are: F, generation - | mg/kg; at the 5 mg/kg dose body weight effects - 5 mg/kg for reproductive; at the 10 mg/kg dose higher incidenceofstillbom F, generation --puLpesss than | mg/kg, the lowest dose tested, based on body weight effects -5 mg/kg for reproductive effects, the highest dose tested Dronif AscrsmentReporPFS Appendic 5 000065 F, generation - | mg/kg; at S mg/kg reduced litter size, pup viability and growth `The resultsof the 2-generation studies with PFOS and N-EtFOSE are very similar with respect 10 the typesofeffect seen, dose response, and lowest doses that cause effects. Maternal body weight changes are observed in the pre-natal teratology studies and the two generation studies with both chemicals. However, the mortality seen in the perinatal periodoflife has no parallel in the prenatal studies. While modest increases in resorptions were seen in the 2-generation studies, in the main, pup development until the timeofbirth was fairly normal. Gross appearance notwithstanding, the incidenceof pup mortality was severe (at the higher doses) on the day of birth and in the immediate perinatal period. The study design did not permit insight as to the factor(s) that contribute 10 the lethal response. Resultsofthe 2-generation studies indicate that fertility and reproductive performance are not impaired at doses that cause adverse body weight effects on males and females. It is not clear whether the resorptionsaredue to direct effects on the fetus or secondary to altered maternal physiology associated with decreased food consumption and weight gain. APFOS cross-foster study was performed to ascertain the roleofpre-natal, post-natal, or combined exposure on pup mortality and health (RS48). A single gavage dose, 1.6 mg/kg PFOS, was used. Female Sprague Dawley ratsweretreated with 0 or 1.6 mg/kg daily during a 42 days premating, mating, pregnancy, and a lactation periodof21 days. At birth, 25 litters from control or treated dams were cross-fostered with 12 13 control or PFOS treated dams. Thus four groups were established. The resultsofthe study that ended on post-natal day 21 is summarized in Table 412. `Table 4-12. Cross-foster PFOS Study Postnatal Pup Effects During 21 Day Lactation Period" PFOS Exposure' Number Total Percent Litters Pup Gestation Lactation __ Dead Pups Mortality Affected Weight' 0 0 39 16 3 200 0 16 2 sm 20 2 22 16 0 16166 96 10 267 16 16 4m 28 246 *extracted from RS48 refers to daily female dose of0 or 1.6 mg/kg PFOS. "mean weight in Grams on LD 14. Mortality was increased (9.6%) in pup litters whose exposure was solely in utero. Mortality was greatest (19.2%) in pup liters exposed in utero who also nursed treated females. There was no increase in mortality in pup litters not exposed in utero that nursed treated females; body weight gain was reduced. The greatest reduction in weight gain was in pup litters who had in utero and lactation exposure. PFOS serum levels were determined in liters and dams from this study. raf nitsscssmen Repo PFOS- pend 8 000066 These data are summarized in Table 4-13. Table 4-13. PFOS Serum Values at Time of Necropsy (LD 21/22) in ug/mL (ppm) PFOS Exposure' Gestation Lactation Nursing Dams Mean Litters Pooled Mean 0 0 0.05* (12% 0.05% (6) 0 16 8296 (13) 2235 (6) 16 0 202 (13) 5388 (6) 16 16 8897 (12) 89.71 (6) * 0.05 uG/mL is Lower Limit ofQuantitation. ** Number in parentheses is numberofsamples `The data clearly indicate that treatmentof a pregnant dam can result in significant levelsofin utero exposure to POS. This is demonstrated by serum values of about 54 ppm in 21 day old `pups who had only in utero exposure. PFOS also appears to be readily secreted in milk, as. evidenced by pups with no gestational exposure having serum levelsofabout 22 ppm after nursing treated dams. Drawing upon results from a pharmacokinetic study discussed in 4.3.1 (RSS2) it appears that a PFOS fetal serum levelof ~117 ppm just preceeding birth is associated with perinatal toxicity and death, e.g., fetuses from dams with exposure to 1.6 mg/kg PFOS. The premating sera concentrationofdams in this dose group averaged 185 ppm. In summary, in utero exposure to 1.6 mg/kg PFOS via the dam lead to perinatal mortality and reduced growth. In a separate study, matemal exposure to 1.6 mg/kg led to serum levels of 117 uG/mL in fetuses just prior to birth. J utero and peri-natal exposure to 1.6 mg/kg appear to be additive with respect 10 toxic effects and perinatal death in pups. Finally, exposure via milk from mothers receiving 1.6 mg/kg did not cause death although a decrease in pup weight was observed. The serum levels support a hypothesis that the degree and severityof developmental and peri-natal toxicity is directly associated with PFOS concentration. Ongoing Study A study is planned that will assess the role of reduced cholesterol metabolism as a cause of perinatal mortality in rats. 43.5 Genetic Toxicity PFOS. PFOS has been tested for genotoxic activity in a batteryofmicrobial and mammalian systems. These included assays for induction ofgene mutations in Salmonella typhimurium and Escherichia coli, (RS14, RS15, RS16, RS17, RSI8)a test for gene conversion in the D4 strain of Saccharomyces cerevisiae (RS18); an in vitro assay for chromosomal aberrations in human `whole blood lymphocytes (RS21). the mouse micronucleus assay (RS19), and an assay for raf nitsscssmen Repo PFO Append E 000067 unscheduled DNA synthesis (UDS) in primary rat liver cell cultures (RS20). PFOS was negative in all assays in which it was tested. Potassium perfluorooctylsulfonate did not induce reverse mutation at the histidine locus of 5. typhimurium strains TA1535, TA1S37, TA1538, TA98, and TA100, or at the tryptophan locus of E. coli WP2uvrA, and did not induce gene conversion at the try locus in the D4 strainofS. cerevisiae when tested with or without metabolic activation from Aroclor-induced rat liver microsomes at doses up to 5,000 pg/plate (RS15, RSIS). `The diethanolamine salt ofPFOS was likewise without genotoxic activity in typhimurium strains TA1S35, TA1537, TAI538, TA98, and TA100 when tested at up to 5,000 pg/plate, with and without metabolic activation, and in the D3 strainofSaccharomyces cerevisiae gene recombination assay at up to 5% (RS14). Potassium perfluorooctylsulfonate did not induce chromosomal aberrations in human lymphocytes when tested at up to cytotoxic concentrations, with or without metabolic activation by Aroclor-induced rat liver microsomes (RS21). Nor did it induce UDS in primary cultures of rat hepatocytes when tested at up to cytotoxic levels (RS20). In the in vivo mouse micronucleus assay. potassium perfluorooctylsulfonate did not induce `micronuclei in the bone marrowofCrl:CD-1 BR mice given a single gavage doseof 237.5, 450, or 950 mg/kg (RS19). N-E(FOSE, Negative results have been obtained in batteries ofgenotoxicity testsofN-cthyl perfluorooctane sulfonamidoethanol (N-E(FOSE). N-EAFOSE gave negative results in micronucleus assays in rats (RS12) and mice (RS11) at doses up to lethal levels by oral gavage. N-E(FOSE, did not induce UDS in liver cellsofras that had received a single doseof 203, 405, or 810 mg/kg by gavage 2-3 hours earlier, or 15-16 hours carlier (RS13). A mammalian cell gene mutation assay in mouse lymphoma cells (RS10), which the authors considered as providing evidenceof mutagenicity in the presenceofmetabolic activation, suffers from a number of methodological and interpretative problems that render it uninterpretable. These deficiencies include: Inadequate identification of mouse lymphoma test strain; Use of excessive, potentially toxic levels of S9 mix; Useofan inappropriate positive control chemical for the non-activation assay; Poor detection of small colony mutants; Useofexcessively high, toxic concentrationsoftest chemical in the mutation assays; Useofan excessively long mutant expression period (3 days); Useofinsufficiently large numbersofcells for mutation assays; and Over-interpretationofstudy results. N-MeFOSE. N-methyl perfluorooctane sulfonamidoethanol (N-MeFOSE) gave uniformly negative results in an Ames assay in Salmonella typhimurium (RS22), a mammalian cell gene Drath nial scssmen Repos PROS-Appen|d 000068 mutation assay in L5178Y mouse lymphoma cells (RS24), a human lymphocyte chromosome aberration assay (RS23), a at liver cell UDS assay (RS26), and a rat bone marrow micronucleus assay (RS25). 43.6 Any other Human Health Relevant Information Ocular Irritation PFOS was found to be mildly irritating to the eyesofalbino rabbits when as powder. The ocular imitation was limited to the conjunctiva in the six test rabbits. Irritation was noted at the 1, 24, and 48 hour post-instillation reading times. The maximun irritation score was 9.3 out ofa highest possible score of 110 at the one-hour reading. By 72 hours post-instillation the score subsided 10 0.0 (RS1). Dermal Irritation PFOS was found to be non-iritating to the skinofalbino rabbits when tested under conventional Draize procedures. No signsofdermal imitation were observed in any of the test animals at any time during the study period. The primary skin irritation score was 0.0 out ofa highest possible score of 8.0 (RS4). Sensitization No reports on the sensitization potential of POS are available. Human Data `Thereare no known cases of iritation or sensitization associated with human exposure. Conclusions PFOS is potentially a mild iritant on contact with eyes andisnot expected to iitate skin. 4.4 Data from Studies in Humans 4.4.1 Background and Early Medical Surveillance `There have been two major types of initiatives to examine the healthofthe 3M fluorochemical production workforce: periodic medical surveillance examinations and a retrospective cohort `mortality study. There have been no epidemiological studies of the general (non-occupational) population nor have any other occupational cohorts studies been published. Following reportsof the findingoforganic fluorine in sera samples, a fluorochemical medical surveillance program began at 3M's Decatur (Alabama) manufacturing facility in the late 1970s. `The voluntary program has generally consistedofbiennial testsofclinical chemistries, pulmonary function, blood counts, accompanied by biomonitoring of fluorochemical exposure. A total organic fluorine measurement was routinely done until the mid-1990's.A total organic Tr -- ot 000069 fluorine assay measures the amount of fluorine that was covalently bound to carbon in the serum sample and is not specific for PFOS. When test data were available, a company physician reviewed cach employee's result. These physicians did not, and have not, found abnormalities in individuals that they believed were related to fluorochemical exposure. That is, medical `conditions, medications and lifestyle factors adequately explained any observed laboratory abnormalities. 4.4.2 Medical Surveillance Studies Beginning in the mid-1990's, the 3M medical surveillance programs at the Decatur and Antwerp (Belgium) plants incorporated serum measurements of PFOS and perfluorooctanoate (PFOA) rather than total organic fluorine (RSS). High performance liquid chromatography-mass spectrometry was the analytical method used to detect and quantify these chemicals. An aggregate analyses was conductedofthe Decaturand Antwerp male employees participating in 1994/1995 (n= 178) and 1997 (n = 149). (There were too few female employees to afford data analysis.) Sixty-one employees participated in the program during both time periods. Results from hematological, standard clinical chemistry tests and several hormone assays (cortisol, dehydroepiandrosterone sulfate, estradiol, follicle stimulating hormone, 17-alpha hydroxyprogesterone, luteinizing hormone, prolactin, sex hormone binding globulin, free testosterone, bound testosterone, and thyroid stimulating hormone) were analyzed in relation to Serum PFOS levels. During both time periods, serum PFOS levels in 95 percent of the employees were below 6 ppm. `The two plant populations differed by age, body mass index, and alcohol consumption, resulting in differences between the populations in several clinical chemistry parameters. Multivariable analyses adjusted for these potential confounders. When analyzed in aggregate, no consistent significant associations were observed between the employees" serum PFOS levels and the clinical chemistries or hematology parameters for either time period. (Total bilirubin levels appeared to trend downwards; further analysis found that this was restricted to Decatur employees and the values were all within the reference range.) Multivariable regression models were fitted with PFOS level (analyzed as a continuous variable) using linear, as well as nonlinear, transformations in order to maximize the possibility of finding associations between PFOS and the parametersof interest while adjusting for potential confounders. No consistent associations were observed by plant, by year,orby both. As discussed in the toxicology section (4.3), the most sensitive clinical chemistry endpoint in rats and monkeys with increasing exposure to PFOS or N-E(FOSE appears tobe a reduction in serum cholesterol levels. Itisofnote, therefore, that mean serum cholesterol levels in these production workers remained constant or increased with increasing serum PFOS levels. An aggregate analysisofboth plants' HDL levels appeared to show negative association with increasing PFOS level; however, this was confounded by the fact that all the workers with PFOS levelsof6ppm or greater were older than workers in the lowest PFOS category, had higher body mass indices (BMIs), and, in 1997, were only employed at the Decatur plant. Multivariable analyses and stratification by plant found no consistent associations between HDL and PFOS levels. In 1995, hormone values were also obtained from a subsampleofemployees with the higher PFOS measurements. After adjusting for age and body mass index, no significant associations were observed between these hormones and serum PFO levels, with the exceptionof estradiol. The latter quadratic Dra nitsssReport PFOS- pends| @ 000070 association was highly influenced by one employee with high PFOS measurement (12.83 ppm) and a large BMI; removalof this employee from the analysis resulted in no significant association with estradiol. `The results from these analyses suggested that, among these Decatur and Antwerp male fluorochemical production employees, significant hematological, clinical chemistry, and hormonal abnormalities were not associated with serum PFOS levels up to 6 ppm. (It was not possible to draw conclusions regarding the small number of employees with serum PFOS levels >6 ppm.) Limitationsofthese surveillance analyses included its cross-sectional design, the voluntary participation rates of less than 50 percent, the small numberofsubjects exposed at the highest levels and a single hormone measurement, rather than multiple hormone mesurements. 4.4.3 Mortality Studies A retrospective cohort mortality studyofemployees who worked at least one year (1961-1990) at the 3MDecatur manufacturing site was conducted to determine whether the mortality experience of these production workforce was significantly different from that which would be expected [RSS]. A total of 1,957 employees (1,639 males and 318 females) constituted the cohort, which represented 37,915 person-yearsoffollow-up. Only six employees (0.3%) were lost to follow-up. Vital status was searched through 1991 using company records, credit bureaus, Social Security Administration and the National Death Index. A total of 74 deaths were reported and 72 (97%) death certificates were obtained. Observed deaths were compared to an expected number calculated by using indirect standardization techniques with three comparison populations: United States; Alabama; and regional Alabama counties. Analyses were also stratified by whether male employees ever and only worked in the chemical and film plants at the Decatur sie. No statistically significant elevations in Standardized Mortality Ratios (SMRs) were found for any specific causeofdeath or for anyofthe comparisons. Table 4-14 provides the data for the `most common causesofdeath, raf nia ssssmen Repo PFO-spend1 & 000071 Table 4-14. Retrospective Cohort Mortality Analysis for Male Employees of the Coeorveat |ome|rscurt| ere Decatur Chemical Plant (n = 1,050) 95% Confidence AN Nfalgnant Neoplasms `Canocftehre Bronchus, `Trachea, or Lung 7 120.7 485-2487 Despite the excellent follow-upofthe cohort, there were three important limitations to thisstudy: 1) the few person-years of follow-up; specific job exposure matrix, 2) the short latency period; and 3) the lack oa f PFOS- 4.44 Work In Progress 3M, in conjunction with epidemiologists from the University of Minnesota Division of Occupational and Environmental Health, is in the midst ofcompleting an updateofthe cohort mortality study. Several methodological improvements have occurred since the original study, including the computerizationofthe work history record for all past and present employees, `which, in conjunction with information regarding serum fluorochemical levels acquired from `medical surveillance exams and the random sample assessment (described above), will allow for the construction ofa PFOS-specifjiocb exposure matrix. Estimated dateofcompletionofthis udpodnaetaedmosntugdytihse ANnotvweemrbpere,mp2l0o00y.ee(pAopcuolmaptairoanbdlueerteotrtohsepeccotnifviedecnothioarltn`amtourrteaolfitdyesattuhdycecratnifnioctatbee registration in Belgium.) An additional health-related research effort that is scheduled for completion in 2000 is the analoyf sheailtsh chemical and film claims data from plant employees. January Health 1, 1993, through December 31, 1998, of the Decatur claims data are not available for analysis purposes prior to 1993. Clinical Care GroupsTM methodology will be used to group all visits (inpatient and outpatient), procedures, ancillary services, and prescription drugs considered in the diagnosis, treatment, and managementofapproximately 400 diseases or conditions. An episode `will be considered a constellationof one or more claims data records representing an occurrence ofa disease or condition for a particular condition. The observed group claims data will be compared to and gender. an expected number calculated by indirect Corrected for their different age structures, standardization the ratioof the methods observed to to adjust for expected ag e chemical plant claims experience will be compared to the film plant's [Ederer and Mantel, 1974] 000072 45 Initial Assessment for Human Health 4.5.1 Approach to Assessment ePxFpOoSsehdapsobpueleantiiodnenst.ifTihedisininsiteiralumasssaemspslmeesntfrisomfobcoutshedococnuptahteiqouneaslltyioannodfwnhone-tohcecrupaantdiotnoawllhyat erixstke.ntBtohtehleepvieldsemoifolPoFgOicSalfoaunnddainnismearlutmoxsiacmoplloegsy fdartoamatrheosaevapiolpaublleatfioornusspeoisnetahehausmsaesnsmheenatl.th uPnFdOerSstcaonmdeisngtooftbeheprreesleanttivienihmupmoartnasneceruomftfhroosme adivfafreireetnytosfosuorucersc.esSaonmdethmearye iasriasseyfetronmo clear efoxrpoesxaumrpelteo),prwehciulresoortmhoerleecxuploessurtehamt adeygbreadteo aPnFdOmSeittasbeloflitzherotuogPhFuOnSder(dNe-tEetrhmiynleFdOSE Alcohol, einnvvoilrvoinnmgenctoamlpapraitshownasyos.f eIxttiemfaorlt(haidsmrienaissotnertehda)t dtohesetsypkincaolwanpptroobaechastsoocriiastkeadssweistshmaednvte,rse heevaelnthpoesfsfiebctlse wfiotrhPFdoOsSe.s eTxhpeeraipepnrcoeadchbytothbeeptoapkuelnathieornesiunnvodlevreesv,ailnusatteiaodn,,ciosmnpoatraipspornosproifatseerourm lfeovuenlds tihnaetxhpaovseedbepeonputlhaetisounbsj.ectTohfisepaipdpermoiaoclhogisi,cfaolrasnedvetroaxlirceoalsoognisc,alliskteuldyietso wpirtohvisdeergurmealteevrels scientific certainty than the more traditional approach. Ofrnoemrseeavseornalfodriftfheirsecntonscoluurscieos,n shoasthaaltrtehaedysbeereunmnfoitneddi:ngPsFrOefSlercetatcohtealshaunmdaancceuxmpuolsautrees. in blood cMuorrreeonvtleyr,esbteicmaautseed PtoFbOeS3i0s0redlaaytsi,vesleyrapelresvisetlesnti,ntwegirtahteanexeploismiunraetioovnerhatlifm-el.ifeEixntehmuamlandosses, edisfpfeicciualltloy foobrtsauibnsitnafnocremsahtaiovninognmtuhletidpelgereseooufrcveasr,iaabrielihtiyg.hlSyevraruimablleeveolvsearrteilmiek,elayndtoitbeisaofftaren more stable estimate of long-term exposure. Uncertainty is the traditional reduced when risk assessment, based assessments on intra- and are based on interspecies direct comparisonsofserum levels. comparisonsofexternal doses, In AfaDctMorEs tdhiatffaerreengceenseraarle,onfottenchuenmkicnaolw-snpeacnidfiacr,e ianccnaotuunret.edTfhorebPyFtOheSianstsreosdsumcteinotndoefscurnicbeerdtahienrteyin dgroeeastenrotresluifafbielritfyrothmatnhitsheiympdoortwahnetnsoeuxrtceemaolf dunocseertiasiunsteyd.and interspecies extrapolations have oMfohsetalotfhtehfefrecetcsenitnlfyoprrmaotdiuocnedinerpeildaetimoinoltoogsyeraunmd tleovxeilcso;lcougryrednattaanhdavfeutiunrveosltvueddietshehadveevebleoepnment designed to acquire similar typeofdata. ref nia tsssnesRepo PFS sppendic 6 000073 45.2 Health Effects of PFOS and Dose-Response Relationships eDfafteactfsrformomsttuhdeiePsFoOfS3Msefrluumorloecvehlesmiicdaenltipfrioedducitnitohnosweorpkopeurlsathiaovnes.thTushefadrarteavedaerlievdenforaodmverse medical surveillance investigations and from a retrospective cohort mortality study. oBfegpiunlnmionngarinytfhuencltaiteon1,9w70e'rse,pbeirenfnoiramledheomnatwoolrokgeircsalatan3dM'clsinDieccaaltcuhremmiasnturfyactetsutrs,inaglofnacgilwiitty.h tests fUlnuiolritnheeamnidd-wa1s99n0o'ts,PFfOlSu-osrpoecchiefmiicc.alIenxpnoosnueroefwtahes ybeaasresdofotnelsytoinngthdeidleovcecluopfatsieornuaml pohrygsainciicans, report abnormalities they believed to be related to organic fluorine exposures. pIrno1d9u9ct4i/o1n99f5acailnidtieasgawiansianss19e9s7s,edthien rheelaalttihoonsfhmiaplteo esmeprluomyleeevselasto3fMP'FsOSD.ecaItnuradadnidtiAonnttwoetrhpe pstearnfdoarrmdedseotsnofacsluibnsicctaolfcthheemiwsotrrkyerasn"dbhleomoadt.olIongitchael1t9e9s4ts/,9a5sssaaymsplfionrg1117d8ifefemrpelnotyheoersmwoenrees were celvianliucaatlecdheamnidstirny,19o9r7,ho1r4m9ownealreabtnesotremda;lailtliweserweerveolausnstoeceirsa.tedNwoitsihgnsiefriucamntlehveemlastuoplotgoic6apl,pm in beietchaeurosefotfhethseteuxdpyepreirmieondtsa.lSoebrseurmvacthioolnessttehraotlPlFevOelSsawtehrieghneort daoffseecstecda;ustheidsefcilnidniensgiinstshiigsnificant parameter. `Ayea1r9a9t5trheet3roMspeDcetciavteucrohporrotdumcotritoanliftaycislittuydyreovfea1l,e9d57noemstpaltoisyteiecasllwyhsoighniafdicwaonrtkeeldevaattiloenasstionnreisk for any specific measurements. causeofdeath, including cancer. This study did not include PFOS serum iTnhfeosremasttiuodinesfoorfripsrkodauscsetsisomnewnto.rkeFrisr,st,altthheoyugihnvloilmvieteddirienctseavtetreamlptwsaytso,idpernotviifdyeaidmvpeorrsteahnetalth eefxfaemcitnsaitnitohneofmcoasntcheirghalnydeoxtphoesrecdauhsuemsaonfmpoorptulaaltiitoyn,s.butSeaclosnoda,wtihdeey riannvgoelovefncoltinoincallypaanrameters that are likely to the same time, it rmeupsrtesbeentrseecnosgintiizveedintdhiatcatthoersstoufdiaeddveprospeuleaffteicotnssbaarseendootnreepxrpeesreinmteanttivaelofdattah.e At `hgeeanletrha,lapnodpurleaptrieosnenitnwtohamtetnheiyndoonlnyotaviencrlyudleimcihtielddrweany,.theSteulddieerslyn,oowr tuhnodseerswuafyfemrianyg afdrdormesilsl- someof these limitations. rMaobrbietsex(tteenrsaitovleodgaytoanloyn).theAsefdfeicstcsuosfsePdFiOnSthaerienatvraoidluacbtlieonfrtoomthsitsusdeicetsiionn m(4o.n1k),eyresp,eartat-sd,osaen.d uannidmearlgostmuedtieasboolnisNm-Ele(aFdOinSgEtaonPdFNOS-.MeTFhOusS,Echoamvpearbaeteinveintcolxuidceodlobgeycasutusdeiebsootfhtchoemsep:ounds pcroemcpuorsuonrdssaraendduPFeOnStirceoluyl1d0rtehveeaelndwhpertohdeurctaonfyotfhteihremeetffaebcotlsoifsmt(hePFfOoSr)m,erortwmoayPFaOlsSo involve nonoewoarvmaiolraebloeftohnePFinOtSe,rmNe-dEiaXrFyObSrEe,aaknddowNn-pMreodFuOcStsEodremmeotnasbtorlaitteess.aTchoenssiusbtsetnacnytoiafledfafetcatbsa,seand some data suggest that these effects may be due to PROS. Additional study will be necessary to ref niatsssmen Repo PFS-pend1 3 000074 confirm thi initial impression. cIhnorleecsetnetrorlepleevaetl-sd,ocsaeussteudrieedsucintiroantss,iPnFbOodSyawnedigthhetsgeapirne,caunrdsocracuosemploivuenrdesnlraerdguecmeensteraunmd vmaocnukoeliyzsa.tioAnt. thTehheigshaemset pdoasteisemtoesfteedf,fePcFtsOiSs ohbassecravuesdedinuPneFxOpSlaeixnpeodsdueraethsstuidniemsoinnkveoylvsiangnd rats. Similar effects were observed in earlier repeat-dose studiesof PFOS. aBdovtehrsPeFrOeSpraondducNti-vEe(aFnOdSdEevhealvoepbmeeenntaelvaelfufeacttesdifnora ttewroa-tgoelnoegircatcifofnectrastisnturdayt.s anNedirtahbebritcsoamnpdoufonrd has been demonstrated to both compounds affected produce teratogenic effects. In fetal survival and body weight the two-generation studies, gains in dams and fetuses. however, `pTrheesednotseed-riensTpaobnlsee 3r-e5l,atwihoinschhipissfroerprsoodmueceedffbecetlso,wasasidTeanbtlifei4e-d15i.n PAFtOSthidsotsiimneg, stthuediNe-s,MaerFe OSE arensdulNts-,Eb(uFtOaSreEndoattas,ufafsicsiuemnmtlayrciozmepdleinteSetcotbieonuss4e.d2.f3oraqnudan4t.i2t.a4,tiavreeaunasleydsitso.confirm the PFOS Dra nilAssesmentReportPFOS Appen|d 6 000075 `Table 4-15. PFOS Toxicity Data Concentrations, and for Mammals: Observed Cumulative Dose Effects, Serum and Liver PROS |} Group Observed Serum PFOS |(Li<ve4r PPFEOASS|Cumulati.ve | Concentration Dose | Feet pm) (pp.m) (mee) 26-week Capsule-Dosing Study in Cynomolgus Monkeys [Olsmgkgd NOEL TT 8 | wl a3 hepatocyte enlargement 137 females males 0.75 mg/kg/d Dfoerat2h6omraelaersly sacrifice > 150, <300 14-Weck Dietary Study in Sprague Dawley Rats > 100, <137 l= i hypertrophy and vacuolization [S2O0ppppmmFMeamleasles [|NHeOpaEtoLcellular| a1s34] hypertrophy and vacuolization; decreased cholesterol; increased AAT hypertrophy and vacuolization s5e99a.9s3] 33] 0.4 mg/kg/d Dam [NOEL 4714500 (n= perme [OR yihee EG 5) perveen Jom eee | EG 1.6 mg/kg/d Dam | Slight body weight 61)852140 (n= GE reo[FS pEGer [ev [wre] ra itlFst Ror FOS Append B 000076 Oberg | Serompr0s|FERS |Comune `Table 4-15.CoPncFeOnStrTaotxiicointsy,Daantda CfourmuMlaamtmiavlesD:osOebserved Effects, Serum and Liver PFOS [ T Liver PFOS G[ roup | Effect Concpernitmreaytion n (Dhosee 1.6 mg/kg/d Dam |Sight body weight " 1582866 (n= pm) EG 4 32 mg/kg/d Dam |Body weight 368236 (n= PM 16) 3.2 EG mg/kg/d Fetus Stillbirth, survival 191+264 (n= 6 N/A| 32mg/kg/d Dam EG Body weight 180+41.5 (n= 5 24) ! PM = Pre-Mating, afier 42 daysofdosing; and EG = Endof Gestation, day 21 ofgestation pExpammi(nhaytpieorntorofpThaybalned4v-a1c5uorleivzeaatlisonthiant tthhee elifvfeercstosfofmaPlFeOrSatoscicnurtrhien1g4a-twseeerkusmtuldevye)lsreopfr4es5e.n6ts tlhiveermiefnfiecmtusminemffaelcet lraetvselisfo1r7.th9ipspcmo.mpoTuhnedN.OTEhLe Nfoor Othbisseerfvfeecdt EifnfefcetmaLleeverlat(s NisO6E2L.)9 fpoprmt.heItseis dneoctleiwnoerstihnycthhoaltesttheerolilvelreveeflfsecatrseaarlesonootbsoebrsveerdveidn imnomnoknekyesyast usnetrilumselrevuemlsleovveelrs e1x0c0epepdm1.00 ppm; oRfedcoosvienrgy astnuddiseesruinmmcohonlkeesytesrohlavleevselhsorwentutrhnattothneorhmeapla.tiTcheenlNaOrgEeLmenftrormestohlev6es-muopnotnhcmesosnaktieoyn study is 85 ppm (serum PFO), dPauypsosufrdvoivsailnigs bauftfepcrtee-dmaatdivnegr.selTyhwehNeOnEdLamfosretrhuismelfefvecetl,s mreeaacshur1e8d5 ipnpdma,mmseaatsuthreedsaamfteerpr4e2- `mating time, is fetal effects are 47.1 not ppm. Thus, although the serum levels in observed unless the dam enters pregnancy dams with declines a serum during gestation, PFOS levelof ca the p18p5mpipnmt;hethreatpduapsmowifalldbaemtahkaevniansgtahseerreulemvalnetveNloOfEuLptfoor4a7s.s1espspinmgapreerinnoattaalt erfifsekc.tsT.hus, 47.1 `The NOELS from the animal studies useful for assessing human risk are shown in Table 4-15. [rr -- @ 000077 Table 4-16. NOELS from Animal Studies to be Used for Initial Assessment of Human Risk meres om [TT] NOEL (PFOS Serum Level)| Source Effect at Next Estimated Higher Serum Level| Cumulative Dose 17.9 ppm Td-week, repeai-dose,| Liver enlargement, |~17 mg/kg WT Tppm 85 ppm 2-generation reproduction, rats Reduced fetal survival | 16.8 mgkg | as measured in dams, pre-mating 6 month, `monkey repeat-dose, | Liver enlargement; decreased cholesterol | 27.3 mg/kg levels 4.5.3 Other Experimental Data Related to Health Effects PviFvOoSt,esNts-Efo(rFgOeSnEo,toaxnidc Npo-teMntciFalO.SEThhearveeisbeneonesvuibdjeenccteeodfatonayn sexutcehnspoitveentbiaatltefroyrotfheisnevitro and in compounds. w`Thheetsheesrutbhsitsaenfcfeesctarheasalasnoyrerlealtaitvieolnyshwiepatko itnhdeuocbesresorvfepdertooxxiicspormoepesritniersoodfenttsh.eseItciosmnpootukndnso.wnAt stheivsertailmet,yptehseomfecexhpalnoirsamtosryunidnevrelsytiingagttiooxniscitthyatamreanyotbeugnidnertsotsohode.d l3igMhthoanshuondwerthceosnescidoemrpaotiuonnds produce toxicity. 45.4 Initial Assessment of Risk Occupational Exposures and Risks ShaevreumexlheivbeiltseodflPevFeOlsSininth3eMrapnrgoeduocft1io0n-1w3orpkpemr.s aDvierreactgestluedsisetsohafnp2ropdpumc,tiaonndwsoormkeerwsohrakveers rheevmeaatloeldogniocaelviadnednccleoinfiecxalcechsesmimsotrtrayltietsytsaandndnobyevaisdseaynsceooffe11ffdeicftfseraesntmehaorsmuorneedsb,yatstsaenrduamrd PFOS levels. levels up to Within the l6impiptmat.ioSnseorfutmhecshoelessttuedireosl,ltehvieslsinafroernmoattiaofnfescutgegdesintsthtihsatrawnogrekoefrssearruemnoPt FatOS trhiastk aPtFtOhSe siesrausmsolceivaetlesdrweipotrhtesdo.meAneifmfeacltssttuhadtiewsoouflPdFnOoSt,beN-eExpteFcOtSeEd,toanbde Nfo-uMnedFinOSthEe reveal occupational health studies animal studies, as shown in because of lower serum Table 4-16, range from PFOS serum concentrations. The NOELS from levels of 17.9 ppm to 85 ppm. the tAhseummoisntghtihgehlnyonex-phousmeadnwporrikmeartse biseatrakseenruasmtlheeveblesstapapnriomxailmmatoedleyl1f5orpeefrfceecnttsoifn thhuemNanOsE,Lthaennd tahveerraegsueltwsorfkreorm ltehveel1s4a-rweee5k0 rtaitmsetsudlyo,weprrotdhuacntithoenNwoOrEkLerienxmpoonskuereyss.areO,nattthheeoutpheprerhaenndd,, umsoirneg than one-hoaftlhfe NOEL and, on average, are about 10 times lower than the NOEL. rAesduecxepslamianendyoeafrltiheer,utshuealdiurneccteritnatienrtsipeescaiesssoccoimapteadriwsiotnhsionftseresrpuecmielseveexltsrarpaotlhaetriotnh,anmoexsetrnal dose Dre tilAsset Ror FOS-Appeic Ed 000078 seisgpneicfiiaclalnyttfhroascetiaosnosfoctihateedunwcietrhtaAinDtyMEfacdtiofrfsetryepnicceas.llyThuisse,ditnoteuxmt,rarpeodluatceesftrhoemnaeneidmaflosr ato hbuemlaonws).areMogreeneorvaelrl,yulnacregretratihnatny tfhaocstoersusuesdedfofrowrotrhkeegrenpeorpaulla(tnioonn-so,cbcuepcaatuisoenatlhe) plaotptuerlaarteionnot(see expected to exhibit the same high degree of variability in sensitivity to toxic effects. pLirtotdluecsteirounmwoPrFkOerSsdaarteaeaxrpeoasveadiltaobluenrfeoarcotcecdu,pcaotnicoennatlreaxtpedossutraertsinign mvaatreiroiuaslsu.seTrhfeacimlaijtioersi.t3yMof dreoswindsuatlreuanrmeawcotrekdersstaarrtienegxmpaotseeridaltotfhaltuocroouclhdembiecaalbsporrobdeudctasndthmatettaybpoiclailzleydctoontPaFiOnS.lessAlthtahnou1g%h iltarsgeeermssafleitkyelmyatrhgaitnssucthhawnodroke3rMs epxrhoidbuicttlioownewroerxkpeorss,urtehilsevceolnsc,launsidotnhecraenfonroetwboeufludlldyemonstrate dproeccuumresnotrseda.reThhaendslteudd,yosefemnosnt-oprsoudpupcotritoint workers in 3M's Japanese facility, where PFOS. General (Non-Occupational) Exposures `bTlhoeodcubrarennktslyreavveaaillsabtlheatdantoan-forcocmupsaatmipolnialngeoxfpobsluoroedsftrooPmFsOelSecrtaendgheufmraomn cpao.pu0l.a0t1io10ns0.a1ndppfmr,om a`sTsheocuipapteedr aednvdeofrstehiefsfercatnsgienitshaeboocuctuGpa0ttiiomneasl lstouwdeiers.thaInt tisheallseovealbo(6utpp1m80)tfoo8un5d0 ttoimbeeswliotwheorut tinhtaenrstpheecNieOsEcLomSpafrriosmotnhseofratsaenrdumnolnev-ehlusmraendupcreismuantceersttauidinetsi,esrersepleactteidvetloy.ADAMgaEind,iftfheerednicreecst. `mTeamkbenertsogoetfhtehre, gtehneedraatlapforpoumlahtiuomnaanreansdubasntainmtailalsltyudbieelsoswuglegveesl!stahsastoPciFaOteSdsweirtuhmadlveveerlsseienffects. 4.4.5 Uncertainties in Assessment and Work in Progress `The initial assessment presented above is based on a based on an interspecies comparisonofserum PFOS substantial levels and bodyof health is more certain effects data. than typical It is aunscseerstsamiennttys,trwahnsilcahteasrteobaasneededonfocrrsosmsa-lslpeercuinecsecrtoamipnatryisfaocntsoorsffeoxrtcermoasls-dsopseecsi.esTehxitsrarpeoldautcieodns. aInbolvigehtshoofutlhdisncootnbcelucsoimonp,artehedmwairtghitnhsesleapragreartmiangrgNiOnEsLoSbssefrrvoemdhourmuasnedexinpotshuermeolreevetlyspidceaslcribed assessment. Trehdeucleimditwahteionnsadadsistoicoinaatledepwiidtehmitohleougsiecaolf ihnuvmeastnigdaattiaonhsaavree aclormepaldeytebde.enRiedseunlttifsiefdr,oamncdhrwoinlilc.be: rroedgeanrtdisntgudtiheeseofffePctFsoOfScahnrdonNi-cEetxFpOosSuEreasrewsitlilllbuencdoemreevaavlauialtaibolne. inDetfhienfiuttiuvree.coMnecclhuasniiosntsic understanding ofoffspring in of the underlying causesoftoxicity, particularly the two-generation study is under study. those relating to reduced survival Ahdudmiatinosnearla.daTthaeardiesftorirbtuhtcioomnoinfgPpFeOrtSailneivneglstoatchceorbdlionogd tloevaegles, agnednddeirs,trainbdutgieonoogfrapPhFiOcSloicnation will will be available for future assessments. As add substantially to understanding this detailed area. in Section 4.2.4, several additional studies Dra ilAsse Ror EOS Appeic 7 000079 5.0 CONCLUSIONS AND RECOMMENDATIONS b`TohdisyorfepdoarttasurmemlaartiinzgeshutmheaninfaonrdmaetnivoinrothnamtenistaalvaielxapbolseaurseosftJouPlyFO20S, 2000. There is a and the possible substantial biological oefcfceucptastioofnatlhesaendexnpoons-uorcecsu.paTthiiosnailnfpoorpmualtaitoinonssugagreesntostthaastsohcuiamtaend serum PFOS with adverse levels health found in effects. Similarly, Additional levels found in the environment research now underway will be and in wildlife are used to refine this not associated with initial assessment. adverse effects iOnncglouidnegensvtiurdioensmeinntsaelvesroaulrcaereaasssweislslmeinmtp,rhovuemathnisexinpiotsiaulreas(stehsrsomuegnht soefrarimsek.asuArreemaesnut)n,decrhrsotnuidcy studies in Muchof laboratory animals and this information will be additional tissue measurementsof available in the next year. PFOS from previous studies. DrIti Assent por PF-ApOpeSic " 000050 6.0 REFERENCES 3M Company. Perfluorooctane Sulfonate: Toxicology Data. January 21, 1999. Current Summary of Human Sera, Health and Baril, A., Presented and at P. Mineau. 1996. the 17* Annual A distribution-based approach to Meeting of the Organization improving avian risk assessment. for Economic Cooperation and Development, Washington, D.C. Belisle J, Hagan DF erroncously reported (1978). as 0.02 Anal mg; it Biochem. should be 87, 545 0.02). (Note Error: In this report the blank was BeliJs(1l98e1),. Science 212, pp. 1509-1510. Bisemeier, JA and Harris, DL, 1974. Madison, WI Report T-1117. WARF No. 4102871, WARF Institute, Inc., fCahcatoprmsfaon,rePc.oMl.o,giAc.alFariitsbkroatshseers,smaenndt.D.EnBvriorownn..T1o9x9.8.ChAemcr.i1ti7c:al e9v9a-l1u0a8tionofsafety (uncertainty) ECOFRAM. Assessment 1999. ECOFRAM Terrestrial Methods, Washington, D.C. Draft Report. Ecological Committee on FIFRA Risk Ederer, F, Mantel, N (1974). Epidemiol. 100:165-167. Confidence limits on the ratioof two Poisson Variables, Am. J. TEensvtisrionnEmnevnitrCoannmaednat.al19T9o9x.icGouloigdya.ncEePDSoc1/uRmMe/n3t4.onEAnpvpilriocnamteinotnaalnTdecInhtneorlproegtyatCieonntorfe,SiEnngvlie-rsopnemceinets Canada, Ottawa, Ontario. Guy, WS (1972). PhD. Thesis, University of Rochester, Rochester, NY. pHearufgluhoormo,octBanoained aOcyisdte(iPnF,OAS.),19p9e2r.fluoTrhoeoctmaencehasunlipshmonuincdearcliydin(gPFtOheSAh)ypaonldipcelmoifcibreifcfeacctido.n Biochim. Biophys. Acta. 1128, 65-72. cIkyetdoac,hrT.o,meFPuk-u4d5a0,anKd.,peMroorxii,soL,meEpnroomliofteor,atiMo.n,inKroamtalii,verT.byapnedrflSuuograi,naTt.ed1o9c8t7a.nesuIlnfdouncitcioancido.f In: peroxisomes York, 304-208. in Biology and Medicine, H.D. Fahimi and H. Sics, Eds, Sprger Verlag, New Johnson, J.D., carbon-14 in Gibson, S.J. and Ober, RE. rats afier administration of 1984. Cholestramine-cnhanced fecal ammonium ["Clperfluorooctanoate elimination of or potassium ["Clperfluorooctanesulfonate. Fund. Appl. Toxicol. 4, 972-976. [r---------- 3 000081 Ltouxtitciikt,yRd.a,taan(dwiTt.h Aalsdpeencbiearlgf.ocu19s95o.n ELxDtSraOpvoallauteisofnofracbtiordrss atondbemaumsmeadlisn).caRseepoofrtsNmaol.l6s7a9m1p0l2e0s29o.f National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands. NPraobtbeeinf.eldMaDs.te1r9s98T.heAsins,InUvneisvteirgsaititoynoofftMhineneEfsfoetcat.sofThFelsuios rroescehaermchicpaeorlnfsorLmiveedraFtaattnyd Ascuipdp-oBritneddibnyg Mm NfaatbtbyeafceilddanDa.l,oBguuetefnrhoomff1fa,ttyBaacsisd Nc.ararinedr pSreoatceaitnsA.by1w9y98e.th-D1i4s,p6l4a3c,eamemnmtoofnia umflpueorrfelsucoernotolcytlaanobaetlee,d potassium Accepted, perfluorooctane sulfonate Toxicologist 1998). and other known peroxisome proliferators. (SOT Abstract Nishioka Institute. M,, Strauss Columbus, W. 2000. OH. Design and Structure of the Multi-City Study, Battelle Memorial Pacz, DM, deBianchi, LP, Gil BA, Dapas O, Coronato, RG (1980). Fluoride 13:65. `Pooxtyhgaepnrabgoamdba Va,nd(1r9e7v5e)r.seDeextterramcitniaontitoencohfntioquteasl. flAunoarliynteiicnasleBriuomcahnedmo6t8h:er51b2i-o5lo2g1ical materials by iPnotbhiaoplorgaigcaadla fVl,uidSsi.ngePrroRc,eAdrumroesbtarsoendgWonDad(s1o9r7p1)t.ionDeotferflmuionraitdieonioofnioonniccal(cpiluusmipohnoizsapbhlaet)e.fluAorniadle Biochem 42:350-359. Roach DE (1982). 25,1982. Fluorochemical Control Study. Unpublished report. St. Paul:3M Company, May rSeavmispiloen., BE.SE/.E,RD/.TMM.-8O6p/rRe3s.ko,RiasnkdAGs.seWs.smSeutnetr.Pr1o9g9r6a.m,ToHxeiaclotlhogAiscsaelsbsemnecnhtmRaerskesafrocrhwDiilvdilisfieo:n,1O9a9k6 Ridge National Laboratory, Oak Ridge, TN. SIncvreesetniignagtioInnfoofrHmiatgihoPnroDdautcatioSentVoMlaunumaelChOemficTahles. O1E99C7.DThPirrodgRreavmismieon.OnOEThCeD CSoec-rOeptearriaattive ISncvreesetniignagtioInnofforHmiatgihonProDdautcatiSoentVoMlaunmuaelChOemficTahles. O1E99C7D. TPhirrodgrReavmimseionO.nOETCheD CSoec-rOeptearriaattive Singer L and Ophaug RH (1979). Chem 25:523-525. Concentrationsofionic, total, and bound fluoride in plasma. Clin SPoehrlfelnuiourso,octAa-nKe.,sulEfroinkiscsoacni,d AisMa.potHenotgsitnrdoumce,roCf.p,erKoixmilsaondm,alMfattaynadciDdeBP-ioerxried,atiJo.nW.and19o9t3,her 9ac0t-i9v3i.ties known to be effected by peroxisome proliferators in mouse liver. Pharmacol. Toxicol. 72, Suter, G.W. 1993. Ecological Risk Assessment. Lewis Publishers, Boca Raton, FL. [---- -- a 000082 `Taves D (19684). 1051. Evidence that there are two formsoffluoride in human serum. Nature 217:1050- Taves D (1968). Electrophoretic mobilityofserum fluoride. Nature 220:582-583. cThaavreacsteDr,izaGtuioyn.W,In:BrFeilyleWrR,(e1d9s7.6).BioOcrhgeamniisctrfylIunovroolcvairnbgonCsaribnohn-uFmlaunorpilnaesBmoan:ds.PreWvaaslheinncgetoann,d DC:American Chemical Society, pages 117-134. UflbueolrocFhAe,micSaolrse,naspornelSiDm,inaRroyarcehporDt.EA(m198I0n)d. HygHeAaslstohc sJ.ta4t1u:s58o4f-5p8l9a.nt workers exposed to UReSs.eaErcPhA.and19D9e8v.elGoupidmeelnitn,esU.fS.orEEncvoilroognimceanltaRlisPkroAtsescetisosnmeAngte.ncEyP,A/WGa3s0h/inRg-t9o5n/,00D2.FC.. Office of USS. Environmental EPA/630/R-95/02F. RPirsokteAcstsioenssAmgeenntcFyo.ru1m9,98U..SG.uiEdPeAl.i,neWsasfhoirngEtcoonl,ogDi.cCa.l Risk Assessment Wallace K.B. and biocenergeticsofrat Starkov A. 1998. liver mitochrondria. The Dept. effect of perfluorinated arylalkylsulfonamides on ofBiochemistry and Molecular Biology, University ofMN Schoolof Medicine. Duluth, MN 55812, USA. Supported by a grant from 3M Company. fYlaumoraimneotinowGh,olYeosbhliotoadokefKh,umSaatno mTa,leK. imAunralaytTicaanldBiAoncdhoemT (1989). Distribution 182:371-376. and forms of CT------a-- 7s 000083 APPENDIX I SUMMARY REPORTS FOR PHYSICAL/CHEMICAL PROERTIES CONTENTS Reference 55 Reference 57 Reference 58 Reference 59 Reference 60 Boiling Point Melting Point Vapor Pressure Octanol/Water Coefficient Air/Water Partition Coefficient Water Solubility yp -- I) 000084 BOILING POINT TEST SUBSTANCE Identity: Perfluorooctanesulfonate; may also be referred to as PFOS or FC-95. (1Octanesulfonic acid, 1,1,2,2,3,3,4,4.5,5,6,6,7,7,8,8,8-heptadecafluoro-, potassium salt, CAS # 2795-393) Remarks: Testing was not conducted. Boiling point would be in excess of 400C. Draft AssesmentReport PROS- Appendic 12 000085 MELTING POINT (Reference No. 55) TEST SUBSTANCE Identity: Perfluorooctanesulfonate; may also be referred to as PFOS or FC-95. (1- Octanesulfonic 2795-393) acid, 1,12.2,3,3,4,4,5,5,6,6,7,7,8,8,8-heptadecafluoro-, potassium salt, CAS # SRaemmpalreksw:asTshteorteedstusnudbesrtaanmcbeieins ta cwohnidtietipoonwsdeprr.iorStaomtpeslteinwg.asPutraikteyndfertoemrm3inMedlottonbuemb9e0r.4291%7.by LC/MS, 'H-HMR, "F-NMR and elemental analyses techniques. METHOD Method: OECD 102 GLP: Yes Year completed: 1998 Remarks: prior 10 use Study using utilized a Biichi Melting Point B-540 anthraquinone and 1.8-naphthalimide. instrument, calibrated and inspected just RESULTS Melting point value in C: 400C (No melting observed). Decomposition (yes-temperature C/ no /ambiguous): No Sublimation (yes/no/ambiguous): No R`meamxairmkusm: spMeecaisfuicraetmieonntfsoor fthtehienmsetlrtuimnegntpuosiendt./ mFeilnteindgrorpalnegtse wweerree nloitmiotbesdetroveZd40t0oCaIdCh,ertehe uniformly or otherwise to the wallsof the melting point tubes. CONCLUSIONS `RTehmeamreklsti:ngWphoiilnet/nmoelmteilntginrgaongfetwheastenstotsuobbsstearnvceedwaansd etvhiedreenfto,redicsocuolldornaottiobneofdtetheermtiensteds.amples was observed. ose. The white powder tumed to a light brown and eventually black as temperatures Submitter: 3M Company, Environmental Laboratory P.O. Box 33331 St. Paul, MN 55133 DATA QUALITY Reliability: Klimisch ranking 1. RraEtFiEiRaEsNsCsES Repos PROS-pend| 3 000056 Study conducted Maryland. at the request of 3M Company by Wildlife Intemational, Ltd. of Easton, OTHER Last changed: 5/3/00 rat Iti Assn: Ror PFS. ppeic 4 000087 VAPOR PRESSURE (Reference No. 57) TEST SUBSTANCE Identity: Perfluorooctancsulfonate; may also be referred to as PFOS or FC-95. (1Octanesulfonic acid, 1,1,2.2,3,3.4,4,5,5,6.6,7,7,8,8,8-heptadecafluoro-, potassium salt, CAS # 2795-39-3) Remarks: The test substance is a white powder. Sample was taken from 3M lot number 217. Sample was stored under ambient conditions prior to testing. Purity determined to be 90.49% by LC/MS, 'H-HMR, "F-NMR and elemental analyses techniques. METHOD Method: OECD 104, U.S. EPA OPPTS 830.7950 GLP (Y/N): Yes Year completed: 1999 Remarks: Determinationofthe vapour pressure was done by using the Spinning Rotor Gauge `method. RESULTS Vapor Pressure: 331X10* Pa Temperature C: 20C Decomposition (ves/no/ambiguous): No Remarks: The measured vapour pressure was repeatable. CONCLUSIONS uRseimnagrtkhse:spTihnneinvgaproortoprrgesasuugreemoeftthhoedt.est substance was determined to be 3.31X10* Pa at 20C Submitter: 3M Company, Environmental Laboratory, P.O. Box 33331, St. Paul, Minnesota, 55133 DATA QUALITY Reliability: Klimisch ranking 1 REFERENCES Study conducted Maryland. at the requestof 3M Company by Wildlife Intemational, Ltd.ofEaston, OTHER Last changed: 5/3/00 Or niaAssesment ReportPROS Append Is 000088 OCTANOL/WATER PARTITION COEFFICIENT (Reference No. 58) TEST SUBSTANCE Identity: Perfluorooctanesulfonate; may also be referred to as PFOS or FC-95. (1Octanesulfonic acid, 1,1,2.2,3,3,4.4,5,5,6,6,7,7.8,8,8-heptadecafluoro-, potassium salt, CAS # 2795-393) Remarks: The test substance is a white powder. Sample was taken from 3M lot number217. Sample was stored under ambient conditions prior to testing. Purity determined to be 90.49% by LC/MS, 'H-HMR, "F-NMR and elemental analyses techniques, METHOD Method: OECD 107 GLP (Y/N): See Remarks Year completed: Study completed 1999. Report completed 2000 Remarks: A feasibility test was conducted to determineif the physical propertiesofthe test substance were compatible with shake flask methodology proposed for use in an n-octanol/water partition coefficient determination. Upon completionofthe test procedure, adefinitive partition interface was not obtained. Instead, a beige/white emulsion was observed throughout the sample. RESULTS Log P,,;: Not determined. Remarks: The observation ofan inseparable emulsion in the preliminary test precluded conduct ofa definitive test, as indicated in the protocol (No 454/120298/107F/SUB454, 3M Lab Request U2723). Therefore, a study cancellation report was generated by the laboratory conducting the testing after consultation with 3M. CONCLUSIONS The study substance exhibits physical/chemical characteristics that make determination of the noctanol/water partition coefficient infeasible by the Shake Flask Method. Submitter: 3M Company, Environmental Laboratory, P.O. Box 33331, St. Paul, Minnesota, 55133 DATA QUALITY Reliability: Klimisch ranking NA. Study not feasible. raf niAssen epor PFO spend 1s 000089 REFERENCES Study conducted at the requestof 3M Company by Wildlife Intemational, Ltd. of Easton, Maryland. OTHER Last changed: 5/3/00 railAsset Ror PFOS- ppeic 5 000030 AIR/WATER PARTITION COEFFICIENT (Reference No. 59) TEST SUBSTANCE Identity: Perfluorooctanesulfonate; may also be referred to as PFOS or FC-95. (1Octanesulfonic acid, 1,1,22,3,3,4.4,5,5,6.6,7,7,8,8,8-heptadecafluoro-, potassium salt, CAS # 2795-39-3) Remarks: The test substance is awhite powder. No information was recorded on the purity. METHOD Method: There is no standardized methodology used to determine this value for regulatory purposes. The experiment was designed by Dr. Richard Purdy of 3M's Environmental Laboratory and Don MackayofD. Mackay Environmental Research Limited. GLP (Y/N): No Year completed: 1999 Remarks: The following method was devised and used: `Weigh approximately 0.01 gram of the test substance directly into a tared 250-mL Pyrex" beaker. Record weight. `Transfer 200 mL ofNANOpure water into the beaker using a Class A glass volumetric: pipet. Prepare solvent blank sample. Using a gas-tight syringe, transfear 250 uL aliquot of NANOpure water into a 25-mL Class A glass volumetric flask partially filled with 50% methanol / 50% ammonium acetate buffer reagent. Bring to volume with 50% methanol / 50% ammonium acetate buffer reagent. Ampulate in an amber glassautosamplervial. + Mix and sonicate the test substance in water sample (50 ug test substance/mL. target nominal concentration) for approximately 10 minutes to ensure dissolutionof the test material. + Prepare the control sample. Transfear 250 pL. aliquotof the test substance in water sample into a 25-mL Class A glass volumetric flask partially filled with 50% methanol / 50% ammonium acetate buffer reagent. Bring to volume with 50% methanol/ 50% ammonium acetate buffer reagent. Ampulate in an amber glass autosampler vial. + Place the test substance in water sample beaker on a hotplate and bring solution to a boil. After approximately 10 mLs (5%)ofwater has evaporated, remove beaker from hotplate and cool to room temperature in an ice-water bath. Transfer contentsof sample into a `graduated cylinder and record actual volume. + Process a 250 uL aliquotof sample as described above for solvent blank and control samples. + Retum sample to original beaker and bring sample to boil Repeat steps 6-8 until sample has evaporated to 100 mLs. Submit all ampulated samples for LCMS analysis. Dre IttAssn Reon FOS ppenic Is 000091 RESULTS KTeimpe0rature C: Not recorded. Remarks: *Don Mackay provided the following interpretationofthe analytical results: "As interpret the lab results they established an initial concentrationof 50 mg/L in 200 mL. water then distilled off 10 mL aliquots and analyzed the residue. They then calculated the percentage of the original test substance present which remained in the beaker unevaporated. These `percentage recoveries'; ranged from 136 to 105 with no real trend. I conclude that the f`emsetassuurbisntganlcoewdaiidrn-owtateevrappaorrtaitteiotnocoaenfyfimceieanstus.rabIlt ecaenxtbenet.shTohwins tihsaat ivfewryatseernsaintdivtehmeestohluotdeof evaporate equally (e.g, the contents do not change in composition as would occur with an azeotrope) then K,,, or H is identical for water and the solute. For water,H is approximately 2400 Pa (approximately 20C) divided by 55000 mol/m' or 0.044 Pa m/mol or a K,, of about 2 x 10. The test substance must thus have a K,, considerably less than this, i.c. less than 2 x 10. Its thus essentially non-volatile from aqueous solution. This is probably becauseofits ionic nature. The simple expedient is to assign it a K,,, of zero, i.e. is a type 2 involatile chemical in our nomenclature." DATA QUALITY Reliability: Klimisch ranking 2. Data has limited reliability. Sample purity was not noted. Study temperature was not recorded. CONCLUSIONS `Testing indicates this substance is essentially non-volatile from aqueous solution. Submitter: 3M Company, Environmental Laboratory P.O. Box 33331 St. Paul, MN 55133 REFERENCES Study conducted at the request of 3M Company by Wildlife Intemational, Ltd. ofEaston, Maryland. Study review by Don MackayofD. Mackay Environmental Research Limited, OTHER Last changed: 5/1/00 Of niatscssmenRepo FOS-Append 19 000092 WATER SOLUBILITY (Reference No. 60) TEST SUBSTANCE Identity: Perfluorooctanesulfonate; may also be referred to as PFOS or FC-95. (1Octanesulfonic acid, 1,1,2.2,3,3,4,4,5,5,6,6,7,7,8,8,8-heptadecafluoro-, potassium salt, CAS # 2795-39-3) Remarks: The test substance is a white powder. Sample was taken from 3M lot number 217. Sample was stored under ambient conditions prior to testing. Purity determined to be 90.49% by LC/MS, 'H-HMR, "F-NMR and elemental analyses techniques. METHOD Method: OECD 105, OPPTS 830.7840, and 40 CFR 796.1840. GLP (VIN): Yes Year completed: Study completed 1999. Report completed 2000 Remarks: The definitive test consistedofequilibrationof an excess amountoftest substance with NANOpure water at 30C followed by equilibration at 20C and analyzing subsamples by high performance liquid chromatography with mass spectrometric detection (LCMS). NANOpure water is equivalent to ASTM Type Il Designation D1193-91. RESULTS Value (mg/L) at temperature C: 519 mg/L at 20+ 0.5C. Descriptionof solubility: Slightly soluble. Remarks: Triplicate subsamples were removed from the appropriate bottles afte one, two and three daysof shaking in a water bath maintained at 30 1.0C and following one day of a 20 + 0.5C equilibration period. Analysis of aqueous subsamples after one day had a mean analytical result of 459 mg/L (SD = 8.96, CV = 1.95%). For subsamples collected afer two and three days, the mean concentration were 537 mg/L (SD = 27.6, CV = 5.14%) and 501 mg/L (SD = 64.2, CV. = 12.8%), respectively. CONCLUSIONS `The Day 2 and Day 3 mean solubility concentration were within 15%ofeach other and were averaged to obtain the overall mean Solubility concentration. The overall mean solubility concentration of the test substance in NANOpure water was 519 mg/L (SD = 48.3; CV = 9.31%; N=6). Submitter: 3M Company, Environmental Laboratory, P.0. Box 33331, St. Paul, Minnesota, 55133 DATA QUALITY rf niatsssmenReporPFO Append Lo 000093 Reliability: Klimisch ranking 1. REFERENCES Study conducted at the request of 3M Maryland. Company by Wildlife Intemational, Ltd.ofEaston, OTHER Last changed: 5/3/00 rot niaAscssmen Repor PFO pend1 Lt 000094 Reference 71 Reference 73 Reference 75 Reference 77 Reference 78 Reference 79 Reference 80 Reference 84 Reference 86 Reference 87 Reference 90 Reference 93 Reference 184 Reference 185 Reference 503 Reference 504 APPENDIX IT SUMMARY FOR AQUATIC TOXICOLOGY STUDIES (PNECs) CONTENTS Acute Toxicity to Fish, 1999 Acute Toxicity to Aquatic Invertebrates (e.g. Daphnia), 1999 Acute Acute Toxicity Toxicity to to Aquatic Invertebrates (Freshwater the Saltwater Mysid, 1999 Mussel), 1999 Chronic Toxicity to Early life Stage of Fish, 1999 Chronic Chronic Toxicity Toxicity to to Freshwater Invertebrates the Saltwater Mysid, 1999 (Daphnia Magna), 1999 Chronic Toxicity to Early Life Stage of Fish, 1978 Acute Toxicity to Fish, 1994 Acute Toxicity to Aquatic Invertebrates (e.g. Daphnia), 1994 Acute Toxicity to Fish, 1979 Acute Toxicity to Aquatic Invertebrates (e.g. Daphnia), 1991 Acute Toxicity to Fish, 1974 Acute Toxicity to Fish, 1974 Acute Toxicity to Fish, 1996 Acute Toxicity to Aquatic Invertebrates (c.g. Daphnia), 1996 Dra itl sessReport PROS Atchmens wm 000095 ACUTE TOXICITY TO FISH (Reference No. 71) TEST SUBSTANCE OIdcetnatnietsyu:lfPoenrifcluaocirdo,oc1t,a1n,e2s.u2l,f3o,n3a,t4e4;,5m,5a,y6.a6l,s7o,7b,e8.r8e,f8e-rhreepdtatdoeacsafPlFuoOroS-,orpoFtC-a9s5s.ium(Is-alt, CAS # 2795-39-3) R3eMmalrotksn:umbTehre2t1e7st. sSubasmtpalnecewiassaswthoirtede upnodwdeerra.mbiSeanmtplceonwdaitsiotnaskepnriforrotmo testing. Purity determined to be 90.49% by LC/MS, 'H-HMR, "F-NMR and clemental analyses techniques. METHOD Method: OECD 203 and OPPTS 850.1075 Type: Static acute GLP: Yes Year completed: Study completed 1999. Report completed 2000 Species: Pimephales promelas Supplier: Analytical In-house cultures, Wildlife International, Lid., Easton, monitoring: PFOS measured at 0, 48, 96-hours MD Exposure period: 96-hours aStnaatliysstiisc,amlomveitnhgodasv:eraLgCe,,mevtahluoedsocralbciunloamteida,lwphroebnabpiolsistiyblwei,thbynopnr-olbiintear interpolation using the computer software of C.E. Stephan. Test fish age: Approximately 126 days old Length and weight: 35 (30-38) mm, 0.36 (0.21-0.49) g Loading: 0.24 g fish/L. Pretreatment: None Test Conditions Dilution water: 0.45 mm filtered well water Dilution water Hardness: chemistry (during the 131 (128-136) mg/L as 4-week CaCO, period immediately preceding the test): Alkalinity: 177 (176mg-/L1as7C8aC)O3 PH: 83 TOC: <1.0mgL Conductivity: 311 (310-315) mmhos/cm `Smtioxcekd afonrd~t2e2sthsooulrustiporinoprrteopuasrea.tiAofnt:erPmriixmianrgy,sptroicmkarpyresptaorcekdsionluditliuotniwonaswaptreorpoartt2i7onmalgl/yL and diluted with dilution water to prepare the four additional test concentrations. Concentrations dosing rate: Once SEtxapboilsiutryoefvetshseeltse:st2c5hLempioclyaeltshoylluetnieonasq:uarEixatrceomnetaliynsitnagblaepproximately 15Lof test solution; water depth approximately 17.6 cm. Dra iilAssent ReportPROS - tckment 1 2 000096 Number of replicates: two Number of fish per replicate: ten Numberof concentrations: five plus a negative control Water chemistry during the study: Dissolved oxygen range (0 - 96 hours): 7.8 8.8 mg/L (control exposure) 7.7-9.0mg/L (28 mg/L exposure) PH range (0-96 hours) 8.3-8.6 (control exposure) 84-85 (28 mg/L exposure) Test temperature range (0 - 96 hours) 20.4-22.10C (control exposure) 21.3-22.30C (28 mg/L exposure) Method of calculating mean measured concentrations: arithmetic mean RESULTS MNoemaisnuarledcocnocnecnetnrtartaitoinosn:s:Bk<LcOonQt,rol3,.3,3.56,.65,.99.,59,.91,7,126,82m7g/mgL/L Element value: 24-hour LC,, = > 28 mg/L (C.L not calculable) 48-hour LC, = > 28 72-hour LC, =27 (22 - 4m1g)/Lmg(/C.LL. not calculable) 96-hour LC,=9.5 (8.0 11) mg/L All clement values based Statistical evaluation of on mean measured concentrations mortality: Confidence limits for 24 and 48-hours could not be ccoanlcceunlattreadtidoun-eeftofelcatckroelfatmioorntsahliiptyw.asThneot7d2e-mhoonusrtLrCat,e,dvoavleuer ias rqeuaessotniaobnlaeblreanbgeecoaufspeeracent dead. c`aTlhceu2l4ataentdhe487-2h-ohuorurLLCC,,yvaanludesMowveirengdeAtveerrmaigneedfobrytvhies9u6al-hionuterrpLreCta,tion. Probit was used to LAtnda.lyutsiicnaglhmiegthhpoedrofloorgmya:nceAnlailqyuisdescohfrtoemsattosgolruatpihoynswiwtehremapsesrfsopremcetdroamtetWriilcdldiefteeIctnitoenmational s(HaPmLeCa/nMdS)m.ostWhpreonmidneetnertmpienaikngretshepocnosnecefnotrrpaetrifolnuoofrotohcetatensetsuslufbosntaatnecewainstuhseedt.estNsooluattitoenmsp,ttwhaes qmuaadnteittaotqiuoan)ntwiafyso0n.4t5h8e mbags/iLsoifn itnhidsivsitduudayl. iTshomeermiecacnopmeprocneennttrse.coTvhereyoLfOmQat(rliimxitfoorftifications maneaalsyuzreeddcvoanlcuuersrefnrtolmy 8d5u.3rin1g0s1a1m7pl%eofannaolmyisniaslw.asMe97a.s9u.rSeadmvpalleusescoflolrecstaemdplatestetstakiennitaitat4i8on-hhoaudrs ranged from 86.3 to 101%of nominal. from 87.6 t0 98.3% of nominal Measured values for samples taken at 96-hours ranged Cr -- ws 000097 `Summaryofanalytical chemistry data: EN I iii Conenraion 0, 48, and 96-hours, ' Negative [|ARlels<peLct0ivQely, mg/L (Control 5.13 55 56.0555,507, 5.45, 589,570, 99 50..5929,9.47,0.85,9.33,9.70, 182,193, 162 150,156,148, 27 228656.285.270.278, 368, Tw Concenteaton (0 mg/L ; Loa [56 95 [17 106 cBoinocleongtircaatlioobnsaeprpveaatrieodnsnoarfmtaelr.9S6-ohmoeurosr:alFliosfhtihnetshuernveigvaitnigvfeischonwterroel oabnsdetrhveed3.t3ombge/sLweixmpmoisnurge erratically (4/16 in 5.6 mg/L exposure, 10/10in 9.5 mg/L, 4/4 in 17 mg/L) at test termination. Cumulative percent mortality: Mean Measured [mTesgt Concentration ~~ 24-hours [48-hours |72-hours Neg. Control op To Jo To po p jo ps loope ps fJ o ose sf Bo fo fw] MLoorwteasltitcyoonfcecnotnrtartoilosn: cNaounsieng 100% mortality: 28 mg/L [-------- I" 000098 CONCLUSIONS 9`T.h5empgo/tLaswsiituhmape9r5fl%uocroonofcitdaennecseulifnotneartvael9o6-fho8u.0r~1L1 Cmgf/oLr.faTthheead96m-ihnounrownowmaosrtdaeltietrymainndedntoo be effects concentration was 3.3 mg/L. `Submitter: 3M Company, Environmental Laboratory P.0. Box 33331 St. Paul, MN 55133 DATA QUALITY Reliability: Klimisch rankin=g 1 REFERENCES `This study Company. was conducted at Wildlife Intemational Ltd. Easton, MD at the request of the 3M OTHER Last changed: 5/3/00 ra ilAssetReon FOS-chen 1 ns 000099 ACUTE TOXICITY TO AQUATIC INVERTEBRATES (E.G., DAPHNIA) (Reference No. 73) TEST SUBSTANCE Identity: Perfluorooctanesulfonate; may also be referred to as PFOS or FC-95. (Octanesulfonic acid, 1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-heptadecafluoro-, potassium salt, CAS # 2795-39-3) RSaemmpalreksw:asTshteorteedstusnudbesrtaanmcbeieins tacwohnidtietipoonwsdeprr.iotSoramtpelsteinwga. sPutraikteyndfertoemrm3iMnelottonbuemb9e0r.42917%. by LC/MS, 'H-HMR, "F-NMR and elemental analyses techniques. METHOD TGMeeLstPth:otdy:Ypee:sOSEtaCtDic 2a0c2utaend OPPTS 850.1010 Year completed: Study completed 1999. Report completed 2000 Species: Daphnia magna Analytical monitoring: PFOS measured at 0, 24, 48-hours Santaaltyissitsi,camlomveitnhgodasv:eraEgCe,mevtalhuoeds calculated, or binomial when possible, byprobit probability with non-linear interpolation using the computer software of C.E. Stephan. Test conditions Test daphnid source: Obtained from cultures maintained by Wildlife International Ltd., Easton, MD. Identificationof the original brood stock was verified by the `AcademyofNatural Sciences, Philadelphia, PA. Test daphnid age at study initiation: <24-hours Dilution Dilution water: water 0.45 mm chemistry filtered well (during the water 4-week period immediately preceding the test): Hardness: 132 (128-136) mg/L as CaCO, Alkalinity: PH: 178 (176-178) mg/L as CaCO3 83(8.2-8.3) TOC: <1.0mgL Conductivity: 313 (310-315) mmhos/cm Ca/Mg ratio: 35/13.5 Irate 8A us Na/K ratio: 21.3/6.62 Lighting: Colortone 50 fluorescent lights, intensity approximately 359 lux. Photoperiod of 16-hours light, Stock and test 8s-ohlouutirosndsarpkrewpiatrhatai3o0n-:miAnuptreimtraarnysisttioocnpkesroiloudt.ion was prepared in dilution water at91 mg/L. It proportionally was mixedfor ~19.5 diluted with dilution hours prior to use. Afier waterto prepare the four mixing, the primary stock was additional test concentrations. All tEexspt ossoluurteiovnesssaeplsp:ear2e5d0cmleLarpalnasdticcolboerlaeksesr.s containing 240 mLof test solution. The approximate depthof test solution was 6.4 cm. Number of replicates: two g he 600100 Number of daphnids per replicate: ten Numberof concentrations: five plus a negative control Dr nilAssent ReportPROS che wr 000101 Water chemistry during the study: Dissolved oxygen range (0 - 48 hours): 8.68.9 mg/L (control exposure) 86-91 mg/L (91 mL exposure) PH range (0 - 48 hours) 82-85 (control exposure) 8.58.6 (91 mg/L exposure) `Test temperature range (0 -- 48 hours) 19.5-20.201C (control exposure) 193-20.19C (91 mg/L exposure) Element basis: mortality and immobilization Method of calculating mean measured concentrations: arithmetic mean RESULTS Nominal concentrations: Bk control, 12, 20, 33, 55, 91 mg/L Measured concentrations: <LOQ, 11, 20,33, 56,91 Element value: 24-hour EC,, = 82 (81-83) mg/L mg/L 24-hour EC,, =>91 mg/L (C.L. not calculable) 24-hour EC, =>91 mg/L (C.1 not calculable) 48-hour EC,, = 53 (<11->91) mg/L 48-hECoy,u=6r1 (33-91) mg/L 48-hour EC,y= 63 (<11->91) mg/L. All clement values based on mean measured concentrations Sptoastsiisbtliecablyepvraolbuiattainoanl:ysiTsh,etEheC,m,ovvailnugesavaenrda9ge5m%ectohnofdidoernbcienionmtiearlvaplrsowbeabrielictaylcwuiltahtendonw-hleinnear cianltceurploaltaetdiwonheusninpgostshieblceomupsiuntgerthseofBtrwuacree-oVferCs.tEe.egStmeepthhaon.d TbehceaEusCe,,tahnerdeEwCe,r,evlaelsusetshwaenrtewo concentrations with partial mortality or immobility. ALinda.lyutsiicnaglhmieghthpoedrofloorgmya:nceAnlailquyisdescohrfotmesattosgorluatpihoynswiwtehremapsesrfsopremcetdroamtetWriilcdldiefteecItnitoenmational s(aHmPeLCa/nMdS)m.ostWhperonmidneetnetrmpienaikngrethsepocnosnecefnotrrpaetrifolnouofrotohcetatensetsuslufbosntaatnecewainstuhseedt.estNsoolauttitoenmsp,ttwhea.s qmuaadnteittaotqiuoann)twiafys o4n.5t8hemgba/sLisoinfithnidsisvtiudduya.l Tihseommeeriacncpoemrpcoennetnrtesc.ovTehreyoLfmOaQtr(ilixmiftorotfifications maneaalsyuzreeddcvoanlcuuersrefnrtolmy 8d5u.r5intgo s1a1m2p%leoafnnaolmyisniaslw.asMe96a.s2.urSeadmvpalleusescoflolrecstaemdplatestetstakiennitaitat2i4on-hhoaudrs ranged from 92.2 to 115% of nominal. from 91.6 to 106% of nominal. Measured values for samples taken at 48-hours ranged raf nial sscssmens Repos PROS-Aackmes 1 us 0001.02 Summary of analytical chemistry data: CNoonmciennatlraTteisot Measured |0, 24, and Duplicated 48-hours, Values at M|CeMoa%ns"ounredto|P[Noeoftmiiannatl nmgL |Respectively, mel one | Negaive |All <L0Q Control <LoQ 110250,106,115, 125, 109, 117823,181,228,21.6.214, 3 330420,341,340,36.1,313, [53 5s S560.54,499,57.0,630,565, [56 mBigo/lLogtirceaaltmoebnstesrvaaptpieoanrsedafhteearlt4h8y-haonudrsn:orDmaaphtnhirdosugihnouthtetnheegtaetsitvweictohnntorom,ortthaeli1t1y,anidmmtohbei2l0ity coorntorvoelr.t cTlhineiceaflfescitgsnsnootfedtoxiinctihtiys. sFtiuvdeypwerecreentmomrotratlailtiy;tynwoaismmoobbsielrivzeadtiaton48w-ahsounrosteidn attheanneygatetsitve concenration. Cumulative percent mortality: MMeeaasnured Test Cmogn/cLenation|4-10urs |48-hours Negative Control 5 [pe Pp o e Jo po fJ e os Dr iiAssn opr FOS tachment 1 wo 000103 Control response: satisfactory CONCLUSIONS 6T1hemgpo/tLaswsiituhmap9er5f%lucoornofoicdteannceseuilnftoenravtael 4o8f-3h3o-u9r1EmgC/SL.foTrhDeap4h8n-hioaumrangonimamowbaislidzeatteiromninaenddtnoobe observed effect concentration was 33 mg/L. Submitter: 3M Company, Environmental Laboratory P.O. Box 33331 St. Paul, MN 55133 DATA QUALITY Reliability: Klimisch ranking | REFERENCES `This study Company. was conducted at Wildlife Intemational, Ltd. Easton, MD at the requestof the 3M OTHER Last changed: 5/3/00 raf nia AsscssmenReposPFS Atachmen 1 wo 000104 ACUTE TOXICITY (Reference No. 75) TO AQUATIC INVERTEBRATES (FRESHWATER MUSSEL) TEST SUBSTANCE OIcdetnatnietsy:ulfPoenrifcluacoirdo,oc1t,a1n,e2s,u2l,f3o,n3.a4t.e4;,5m,a5,y6,a6l,s7o,b7,e8,r8e,f8e-rhreepdttaodeacsafPlFuoOrSo-,orpoFtCa-s9s5i.um(Is-alt, CAS # 2795-393) SReammaprlkesw:asTshteorteedstusnudbesrtaanmcbeieinsta cwohnidtietipoonwsdperri.ortSoamtpelsteinwg.asPutraikteyndfertoemrm3inMedlottonbuemb9e0r.4291%7.by LC/MS, 'H-HMR, "F-NMR and elemental analyses techniques. METHOD EMnevtihroodn:menTthaelsPtruodtyecwtaisoncAongdeuncctyedSeursiiensg8a50pr~otEoccoollogbiacsaeld EofnfepcrtoscGeudiudreelsionuetsl,iOnePdPiTnSU.NS.umber G85u0i.d1e0f7o5r ;CoOnEduCcDti2n0g3:ToxFiicsiht,yATceusttes wTiotxhicFiitsyheTse,st;MaacnrdoiAnSveTrMtebSrtaatnedsaradnEd7A2m9p-h8i8bai,anSst.andard Test type: Semi-static Renewal GLP: Yes Year completed: Study completed 1999. Species: Unio complamatus Report completed 2000 Analytical Statistical monitoring: Test substance concentrations measured by LCMS methods: LC,, values calculated, when possible, by probit at 0, 48, 96-hours analysis, moving average computer softwareofC_E. method or Stephan. binomial probability with non-linear interpolation using the `Test organism source: Obtained Carolina. Carolina collected from from Carolina the wild. Biological Supply Company, Burlington, North `Test organism age at study initiation: Unknown Test Conditions Dilution water: 0.45 mm filtered well water Dilution water Hardness: chemistry (during the 126 (120-132) mg/L 4-week period as CaCO, immediately preceding the test): Alkalinity: 174 (170-178) mg/L as CaCO3 pH. 83 (8.18.5) TOC: <1.0mgL Conductivity: 321 (310-330) mmhos/em CaMg ratio: 35/13.5 Na/K ratio: 21.36.62 Lighting: Colortone 16-hours light, 8-hours 50 fluorescent lights, intensity approximately dark with a 30-minute transition period. 369 lux. Photoperiod of aStt9o1ckmga/nLd.teIsttwsaoslumtiioxnesdpfroerpaapraptriooxni:matAelpyr2i4mahroyursstopcrkiosroltuotuisoen. waAfsiperrempiaxriendg,intdhielputriiomnawrayter csotnocceknwtraastipornosp.ortAlilontaelsltysdoilluuttieodnswiatphpedairleudticolnewarataenrdtcoolporrelpeassr.e the four additional test DrInitAssent par PFOS sche 1 wn 000105 Exposure vessels: 25 liter polyethylene aquaria `The approximate depthoftest solution was 23.2 containing cm. approximately 20 L of test solution. Number of replicates: two Number of test organisms per replicate: ten Number of concentrations: five plus a negative control `Water chemistry during the study: Dissolved oxygen range (0 96 hours): 5.88.5 mg/L (control exposure) 5.0-8.6 mg/L (79 mg/L exposure) `pH range (0-96 hours) 8.0-8.4 (control exposure) Test tem7p.er9a-t8u.r5e(r7a9nmgeg/(L0 --ex9p6oshuoruer)s) 21.4-21.801C (control exposure) 21.8-23.70C (79 mg/L exposure) wEelreemecnontsBiadseirse:d dMeoardt.aliTthye. nMuumsbseerlsofwiitnhdiovpiednuaslhselelxshiabnidtinnogtclrieniscpalonsidgintnsoogftgeonxtilceiptryoodrding abnormal behavior also were evaluated. Methodofcalculating mean measured concentrations: arithmetic mean RESULTS Nominal concentrations: <LOQ, 5.7, 11,23, 46,91 mg/L EMleeamseunrtevdalcuoen:ce9n6t-rahtoiuornsL:C,,<=LO5Q9,mg5./3L, (1521,-2608, m41g,/L7)9 mg/L pStoastsiisbtliecablyepvraolbuiattainoanl:ysiTsh,ethLeCmSo0vvianlgueasvearnadge95m%etchoondfiodrebnicneoimnitaelrvparlosbwabeirleitcyalwciutlhatneodn-wlhienenar interpolation using the computer software of C.E. Stephan. LAunda.lyutsiicnaglhmieghthpoedrofloorgmya:nceAnlailquyisdeschorfotmeasttosgorluatpihoynswiwtehremapsesrfsopremcetdroamtetWriilcdldiefteecItntieornnational s(aHmPLeCa/nMdS)m.ostWhpreonmidneetnetrmpienaikngretshepocnosnecefnotrrpaetrifolnuoorfotohcetatnesetsuslufbosntaatnecewains tuhseedt.estNsoolauttitoenmsp,t twhea.s made to quantify quantitation) was on the 0.115 basisofindividual mg/L in this study. isomeric components. The LOQ (limit of The mean percent recoveryofmatrix fortifications maneaalsyuzreeddcvoanlcuuersrefnrtolmy 7du3r.i7n%g 1s0a9mp6l.e0%anoaflynsoimsinwaals. 94M.e7a%s.urSeadmpvlaelsuecsolflorecstaemdpaltetsesttaikneintiaatti4o8n-had hours ranged from 81.2 t0 98.9%of nominal. ranged from 88.5 to 130%of nominal. Measured values for samples taken at 96-hours rat ninsss Report PROS tachmen1t ni 000106 Summary of analytical chemistry data: [Nominal Test [Measured Duplicated Values at [Mean Measured (Concentration |0, 48, and 96-hours, , mg/L Respectively, mg/L. Concentration, mg/L [Negative [AI<LOQ [<LoQ [Control 57 547,493,518,5.70,524, [53 526 114,101,112,105,109, [12 154 23 190,168,187,187,229, [20 224 372,406,37.1,395, 482, [40.5 (69.0,74.7,813,77.6,882, [19 85.7 [Percent [of [Nominal 93 87 87 mBigo/lLogtirceaaltmoebnstesrvaaptpieoanrsedafhteearlt9h6y-haonudrsn:ormMaulsstehlrsouignhtohuetntehgeatteisvtewciotnhtrnool,mtohreta5l.i3t,y1o2raonvdertthe 20 tclrienaitcmaelnstigannsdof9t0ox%icmiotryt.alFiitvyewpaesrcoebnstemrovretdaliintythwea7s9ombgse/rLvetrdeaattm9e6nt-.houNros ianbnthoerm4a1lmbge/hLa.vior was noted in these concentrations. Cumulative percent mortality: [Mean Measured Test Concentration mg/L [24 Hours [48 Hours |72 Hours [96 Hours Negative Control ps po he [P b i fen b we] Control response: Satisfactory Dr ni sRes posPFOS n Auschmens1 wn 000107 CONCLUSIONS c`Tohmepploatmaastsuisumwapesrdfleutoerromoicnteadnetsoulbfeo5na9tmeg9/6L-hwoiutrhLaC9S50%focrontfheidFernecsehwinatteerrvaMluosfse5l1,-6U8nimog/L. The 96-hour no mortality concentration was 20 mg/L. Submitter: 3M Corporation, Environmental Laboratory P.0. Box 33331 St. Paul, MN 55133 DATA QUALITY Reliability: Klimisch ranking | REFERENCES `This study was conducted at Wildlife International, Ltd. Easton, MD at the request of the 3M Company. OTHER Last changed: 5/3/00 -- wi 000108 ACUTE TOXICITY TO THE SALTWATER MYSID (Reference No. 77) TEST SUBSTANCE Identity: Perfluorooctanesulfonate; may also be referred to as PFOS or FC-95. (1Octanesulfonic acid, 1,1,2.2,3,3,4.4,5,5,6,6,7,7,8,8,8-heptadecafluoro-, potassium salt, CAS # 2795-39-3) Remarks: The test substance is a white powder. Sample was taken from 3M lot number 217. Sample was stored under ambient conditionspriorto testing. Purity determined to be 90.49% by LC/MS, 'H-HMR, "F-NMR and elemental analyses techniques. METHOD Method: OPPTS 850.1035 Type: Static acute GLP: Yes Year completed: Study completed 1999. Report completed 2000 Species: Mysidopsis bahia Supplier: In-house cultures, Wildlife Intemational, Ltd., Easton, MD Analytical monitoring: PFOS measured at 0, 48, 96-hours Exposure period: 96-hours Statistical methods: LCi, values calculated, when possible, by probit analysis, moving average method or binomial probability with non-linear interpolation using the computer softwareofC.E. Stephan. Test fish age: <24-hours old Pretreatment: None Test Conditions Dilution water: Natural seawater diluted to 20%, with well water, 0.45mm filtered. Dilution water chemistry (during the 4-week period immediately preceding the test): Salinity: 20 (20-20) pH: 82(81-82) TOC: <10mglL Stock and test solution preparation: Primary stock prepared at 8.2 mg/L and mixed for ~22 hours prior to use. After mixing, primary stock solution was proportionally diluted with dilution water to prepare the four additional test concentrations. Al test solutions appeared clear and colorless. Concentrations dosing rate: Once Stability of the test chemical solutions: Extremely stable: Exposure vessels: 2L polyethylene aquaria containing approximately 1000mL of test solution; water depth approximately 6.6 cm. Number of replicates: two Number of mysids per replicate: ten Numberof concentrations: five plus a negative control Feeding: Live brine shrimp nauplii daily Water chemistry during the study: rat niaAsssmns Repors PFOS-rach 1 was 000109 Dissolved oxygen range (0 96 hours): 6.87.4 mg/L (control exposure) 6.87.3 mg/L (5.4 mg/L exposure) pH range (0-96 hours) 8.18.2 (control exposure) 8.1-82 (5.4 mg/L exposure) Drath nt scssmes Repos PRtaOchmSent 1 i 000110 `Test 2te4m2p-e2r5at.u4r0eCra(ncgonetr(o0l--e9x6pohsouurres)) 23.8-24.50C (5.4 mg/L exposure) Methodofcalculating mean measured concentrations: arithmetic mean RESULTS NMoemaisnuarledcocnocnecnetnrtartaitoinosn:s:B<kLcOonQt,ro0l.,571.,1,1.11.,8,193.,0,3.40.,9,5.84.2mgm/g/LL Element val4u8e-:ho2u4r-hLoCur,L=C>,5=.4>m5g./4LmgC./L.Ln(oCtIcnaoltcuclaalbcluel)able) 72-hour LC,y = 4.4 (3.6-6.2) mg/L All element v9a6l-uheosurbaLsCe,dyo=n3m.e6a(n3.0m-e4a.s6u)rmegd/cLoncentrations Setxaptoissutricealdueevtaolutahteiolnacokfomnoratnaaldietyq:uatLeC,c,onvcaelnutersatcioounl-drneostpobnesecaplatctuelrant.edTfhoer 2p4roabintdm4e8t-hhooudrswaosf used to evaluate mortality Analytical methodology: at 72 and 96 hours Analysesoftest solutions were performed at Wildlife International (LtHdP.LuCs/iMnSg)h.igWhhpeenrfdoertmearnmcienilniqgutihdecchornocmeanttoragtriaopnhoyfwtihteh mass spectrometric test substance in the detection test solutions, the smaamdee atnodqumaonsttifpyroonmitnheenbtaspiesakofreinsdpiovnisdeuaflorispoemrefrliucorcooomcptoanneenstusl.fonTahteewLaOsQus(eldi.mitNoofattempt was qaunaanltyizteadticoonn)cwurarsen0t.l1y15dumrgi/ngL sian mtphlisesatnuadly.ysiTshweasme9a7.n4.peSracmepntlerseccoovlelreycotefdmaatttreistx ifnoirttiiaftiicoantihoands mraenagseudrefdrovmal4u3e.s5ftroo7m15.20.%4otfo 7no0m.i7n%aol.f Mneomaisnuarle.d Mvaelauseusrfeodr vsaalmupelsesfotraskaemnpalte9s6t-ahkoeunrsatr4a8n-gheodurs from 35.5 10 71.1% ofnominal raf ninsess Report PFOS -Aachen 1 wr 000111 Summaryof analytical chemistry data: Nominal Test (Concentrato. |Measured Duplicate Values at 0,48, Men ed [#407 n and 96-Hours, Respectively, mg/L~ [ mel mL Negative [AlI<LOQ Control [<Loq 0.575,0.622, 0.605, 0.640, 0.391, 0.580 [0.57 [Ls Treawiorone ns Jo 192,199,192, 191,179,190 [Lo [[93052662963331030 bo [82 [582,578.358,585,522, 5.86 [4 percent of 0 [Nominal 52 ja | Je | Ja | Jes | mBigo/lLog(imcaelanobmseearsvuarteidoncsonacfetnetrr9at6i-ohnosu)rst:reaMtymseindtsgrionutphse anpepgeatairveedcnoonrtrmoall,aannddhtehael0t.h5y7daunridng1.1the test. Cumulative percent mortality: Mean Measured CoJneceentration mg/L Negative Control 24-hours |48-hours|72-houurs fh fo hhho] po FE ew be Iss fos | Mortality of controls: None Tr -- is 000112 CONCLUSIONS The potassium 3.6 mg/L with perfluorooctanesulfonate 96-hour a 95% confidence interval of 3.0 ~ L4.C6,mfgo/rL.saltTwhaete9r6m-yhsoiudrsnowamsordteatleitrymiannedd to be NOEC concentration was 1.1 mg/L. Submitter: 3M Company, P.O. Box 33331 Environmental Laboratory St. Paul, MN 55133 DATA QUALITY Reliability: Klimisch rankin=g 1 REFERENCES CThoimspsatnuydy was conducted at Wildlife International Ltd., Easton, MD at the requestofthe 3M OTHER Last changed: 5/3/00 Dr ntsscsRmepeo PnROsS. Asch1e ni 000113 CHRONIC TOXICITY TO EARLY LIFE STAGE OFFISH (Reference No. 78) TEST SUBSTANCE Identity: Perfluorooctanesulfonate; `may also be referred to as PFOS or FC-95. QaOctanesulfonic acid, 1,1,2.2.3,3,4,4,5,5,6,6,7,7.8,8,8-heptadecafluoro-, potassium salt, CAS # 2795-393) Remarks: The test substance is a white powder. Sample was taken from 3M lot number 217. Sample was stored under ambient conditions prior to testing. Purity determined to be 90.49%by LC/MS, 'H-HMR, "F-NMR and elemental analyses techniques. METHOD Method: OECD 210, OPPTS 850.1400 Type: Flow-through chronic GLP: Yes Year completed: Study completed 1999. Report completed 2000 Species: Pimephales promelas Exposure period: 47 days Supplier: Analytical In-house cultures, Wildlife International, Ltd., monitoring: PFOS measured on days 0,4, 7, Easton, 14, 21, MD 28, 35, 42, and 47 Pretreatment: None iStdaetnitsitfiyctalremaetmtehnotdsgr:ouDpissctrheatte-svhaorwieabdlea dsattataiswteircaellaynsailgynziefdicuanstidni2fgfeXre2ncceo(npt<i0n.g0e5n)cyfrtaobmletsheto negative control group. All continuous-variable data were evaluated for normality using `Shapiro-Wilk's test and for homogeneityof variance using Bartlett test. Analysis of variance and Dunnett's Test fish age: test were used to eggs < 24-hours evaluate differences old at test initiation between treatment and control means. Test Conditions Dilution water: 0.45 mm filtered well water Dilution water chemistry (during the 4-week period immediately preceding the test): Hardness: 126 (124-128) mg/L as CaCO, Alkalinity: 172 (170-172) mg/L as CaCO3 pH: 82 (82-83) TOC: <1.0mg/lL Conductivit3y2:1 (315-330) mmhos/cm Stock and test solution preparation: Primary stock prepared in dilution water at 88.4 mg/L `asnodlumtiioxnewdasuntpirlopalolrttiesotnaslulbystdainlcuteeddiwsistohlvdeidluptriioonr wtaotuesre.toApfrteepramriexfiinvge,adtdhietpironiamlarsytosctkocskolutions tathrceoentcoenftoruartidoanyssodfur44i.n2g,t2h2e.1te,st.11.T0,he5.s5i2x,satnodck2s.w76ermeg/iLnj.ecSttedocikntsootlhuteidoinlsutweerrmeipxrienpgarcehdamebveerrys (at arate of 6.0 mL/minute) where they were mixed with dilution water (atarate of 116 mL/minute) to achieve the desired test concentrations. Flow through rate: Approximately six volume additionsoftest water every 24-hours oo " "000114 SEtxapboilsiutryeofvetshseeltse:st9cLheglmaiscsalaqsuoalruitaiofinlsl:ed Extremely stable with approximately 7 Loftest solution with a depth of aapppprrooxxiimmaatteellyy 5107 cmmm. iEnmdbiraymeoteinrcwuibtahti4o2n5cmupms wneyrleoncosncsrtereunctmeedshfraotmtagclhaesds ctoyltihnedebrosttom with silicone attached steoalaanrto.ckTerhaercmupwsitwheraersecuisppreoncdaetdinignmtohteiwoantoefrapcporlouxminmoafteclaych2OrLpmg.lass aquarium and Number of replicates: four NNuummbbeerr ooff fciosnhcepnetrraretpiloincsat:e:sixtwpelunstya negative control dFaeeydsi8ngt;hroLuigvhe4b0ripnoesst-hhraitmcph,nafuepdli3i.tiFmeesd d3aitliymeosnpewreedkadyaydusrainndg t2hetifmiersstd7aidlayysonpowsete-kheatncdhs.. On Not fed for at least 48 weight measurements. hours priotro the terminationoftest to allow for gut clearance prior to `Water chemistry during the study: Diss7o.lv6e8d.o2xmygge/nL r(caonngtero(l0exp4o7sudaryes)): pH 7ra.n6g8e.(20m-g4/7Lda(1y.2sm) g/L exposure) 8.0-8.4 (control exposure) `Test 8.0-8.4 temperature (1.2 mg/L exposure) range (0 - 47 days) 24.4-24.70C (control exposure) Meth2o4d.o3f-c2al4c.u7l0aCti(n1g.2mmega/nLmeexapossuurreed) concentrations: arithmetic mean RESULTS NMoemaisnuarledcocnocnecnetnrtartaitoinosn:s:Bk<LcOonQt,rol0,.105.,104.,300.,290,.600.,571,.2,1.21,4,2.43.,64.m6g/mLg./L Element value: 5-day hatchability NOEC = 4.6 mg/L 4422--ddaayy ppoosstt--hhaattcchh sgurrovwitvhalNNOOEECC==00..3300mmgg//LL All eleme4n2t-dvaaylupeossbt-ahsaetdchonsumreviavnalmeLaOsEurCed= c0o.n6c0enmtgr/aLtions Stotaatnisdtihciaglheervatlhuaant0i.o6n0omfgm/oLrtwalaistyn:otTehvaelsutaatteisdtidcuael dtiofafesriegnnciefifcoarntgreoffwetcht oatncsounrcveinvtarl.atiNoons equal stteasttiesdtiwcaalslysseiegnniffoirchaanttcdhiafbfielrieyn.ce between the negative control and the highest concentration ALntda.lyutsiicnaglhmieghthpoedrofloorgmya:nceAnlailqyuisdescohfrotmeasttosgolruatpihoynswiwtehremapsesrfsopremcetdroamtetWriilcdldiefteecItntieornnational (sHaPmLeCa/nMdS)m.ostWhpreonmidneetnetrmpienaikngretshepocnosnecefnotrrpaetrifolnuoofrotohcettaenset ssuulbfsotnaantceewiansthuesetde.st Nsooluattitoensm,ptthweas `qumaandteittaotqiuoann)twiafyso0n.0t4h5e8bmasgi/soLfiinndtihivsidstuuadly.isTomheerimcecaonmppoernceenntts.recTohveerLyOofQma(tlirmiixt ofofrtifications vaenahlytzteldAcsonscnurrReontrlyFdOuri- nAgtcshmaemnpsleanalysis was 102. Samples collected at pre-test ranged wa from -- 000115 91.4 to 105% of nominal. nominal. Measured values Samples at test initiation for samples taken at test had measured values from 95.5 to 114% of termination ranged from 95.2 to 111% of nominal. Draft nisial Assessment Report PR-taOchmSent 1 22 000116 Summaryofanalytical chemistry data: Nominal Test Concentration, [Measured Duplicate Values at 0,4, 7, 14, 21, 28, 35, 42, and 47 Days, mg/L Respectively, mg/L Negative |All<LOQ Control 0.14 0.1470,.1401,.0.11406,00.14,4, 0.148,0.134, 0.135,0.153,0.143, 0.160, 0.158,0.179, 0.160,0.147, 0.155 0.173, 0.157, 029 0287,0.277,0.270,0.289,0292, 00..239463,,00..23649,1,00.326161,,00.332057,, 00.331195,, 0.313,0.296,0276 0.57 0.571,0.576,0.619, 0.659, 0.597, 0.642, 0.539, 0.535, 0.608, 0.580, 00..567369,, 00..651475,, 00..654463, 0.644, 0.575, 114, 113,121,125,113,123, 1.03, 130, 1.10, 1.19, 1.31, 1.14, 1.24, 1.19, 1.30, 1.13, 1.31, 1.09 23 221,227,2.52,246,243,238, fish all dead at Day 7 4.56,4.40,4.79, 479,446,476, fish all dead at Day 7 |Mean Measured |Percent |Concentration, [of mg/L [Nominal [0.15 107 [0.30 103 105 [12 |24 [4.6 100 Biological Observations 5H.atTchheirnegwseurcecensosaapnpadretnitmeditfofehraetncche:s bAeltlwveieanbltehefattihmeeadtomhiantncohwinetmhbernyeogsathiavtechceondtoronlDaanyd 4toher. PFOS treatment groups. tSouxrivciitvya.l:FiAslhl wfhisihcshudrivdivniontgstuortveisvtetgeernmeirnaaltliyonapappepaeraerdedtonobremsawliwmimtihnngoeorvreartticaslilgynsporiforsutbolethal death. sGrhoowwtehd:noFistsahtiesxtipcoaslleydstiognPiFfiOcSantatrecdounccetnitornaitniotnotsalofle0n.g1t5h,orwe0t.3w0emiggh/tLofrodrr4y2wdeaiygshtpoisnt-hatch comparison to the negative control. Dr IkiAssent por PFS uch 1 wn 000117 Hatchability [Mean Measured [Number (Concentration fof Eges [Number Hatched, [Number Hatched, [Number |Total |Hatched, [Number mg/L Exposed Da3y Day 4 Day 5 Hatched Percent [Hatching [Success Negative 120 74 93 |B B f Control o o s f mfe s ] ef]| B [e hZ s Tso or n] ] fone Larval Survival Mean Measured Percent Concentration, mg/L. p p im so Negative Control Survival, Day 42 Pe i f] 000118 Growth Mean Measured Concentration, [Numberof] Total Length |Surviving Mean + SD, Wet Weight|Dry Weight] Mean + SD, [Mea+n mg/L Larvae [mm mg sD, mg Negative Control 26.5 +0.721 [158 +9.10 [325+ 1.20 26640208[160 +310 [333+ [030% [werosn|iesis 0.900 [M2rzn [00 [5[0p65:039 166:115 [5270 [2 l[a2672200 [1852338 [3545666 bo CONCLUSIONS fF o F] Ffoarth4e2addamyisnpnoostw-shaetxcphosshedowteodpontoasstsaituimstipcearlfllyusoirgonoicfticaannetsurlefdouncattieonast cinontcimeenttroahtaitocnh<,sh0a.t3c0hmingg/L success, survival or growth. The most sensitive endpoint in this study was post-hatch survival, Submitter: 3M Company, P.0. Box 33331 Environmental Laboratory St. Paul, MN 55133 DATA QUALITY Reliability: Klimisch ranking = | REFERENCES This study Company. was conducted at Wildlife Intemational Lid., Easton, MD at the request ofthe 3M OTHER Last changed: 5/3/00 Or kilAsset por PFO-sche 1 nas 000119 C(RHefReOreNnIceCNToO.X79I)CITY TO FRESHWATER INVERTABRATES (Daphnia magna) TEST SUBSTANCE OIcdetnatnietsy:ulfPoenrifcluacoirdo,oc1t,a1n,e2s:u2l,f3o,n3,a4t:e4;,5m,a5y,6,a6l,s7o,b7,e8r,e8f,e8r-rheedpttaodcacsafPlFuoOrSo-,orpoFtCa-s9s5i.um(1s-alt, CAS # 2795-39-3) RSeammaprlkesw:asTshteorteedstusnudbesrtaanmcbeieins ta cwohnidtietipoonwsdperri.orStoamtpelsteinwga. sPutraikteyndfertoemrm3inMedlottonbuemb9e0r.42917%. by LC/MS, 'H-HMR, "F-NMR and elemental analyses techniques. METHOD TMyepteh:odS:emOiP-SPtTaSic85L0i.f1e3-C0y0c,lOe EToCxDiciGtuyideline 21, and ASTM Standard E 1193-87. GLP: Yes Year completed: Study completed 1999. Species: Daphnia magna Report completed 2000 Supplier: Analytical In-house cultures, Wildlife International, monitoring: PFOS measured on days 0, Ltd., Easton, MD 2, 11, 14, 18, and 21. Exposure period: 21 days Sltiavetiysotiucnagl manedthtohdesl:enSguthrvainvadlddraytwaewiagshteovfatluhaetesdurovnivfiinrgstf-igresnte-rgaetnieornatdiaopnhdnaipdhsn,idtsh.e nSuumrbveivraolf ddaattaa wweerree aevnaalluyazteeddufsoirngnoFrimsahleirt'ys uesxiancgt tSehsta.piRroe-pWrioldku'cstitoesntaannddgfroorwhtohmo(lgeenngetihtaynodfvdrayriwaenicgeht) gursoinugpsBatrhtatlewte'rsetesstt.atiAsntiaclaylslyissoifgvniafriicaanntcienacnodmpDaurninselotn'tsottehste wnaegsatuisveed ctoontirdeonlt(ipfy_t0r.e0a5t).menAtll "stTatOisXtiScaTlAtTestRsewleearseep3e.r5f"orstmaetidstuiscialngsoaftpwearrseo.nal computer with SPSS/PC Version 2.0 or Test organism Pretreatment: age: < None 24-hours old at test initiation Test Conditions Dilution water: `microorganisms 0.45 mm filtered and fine particles well water passed through a UV sterilizer to remove Dilution water Hardness: chemistry (during the 124 (120-128) mg/L as 4-week CaCO, period immediately preceding the test): AplHk:alinity: 82(136.90(8136)4-172) mg/L as CaCO3 TOC: <10mglL Conductivity: Ca/Mg ratio: 329 (315-340) 35/13.5 mmhos/cm Na/K Stock and ratio; 213/662 test solution preparation: Primary stock solution was prepared in dilution water at 4pr6immga/rLy.stItocwkassosltuitriroendwuanisiplroapllortteistonsaulblsytadnicleutweadswdiitshsoUlVvedstperriiolrizteod udsiel.utiAofntewratmeirxitnogp,rtehpeare Dra nitAssertReportPFOS tachmen1t [ 000120 five additional stock solutions at test solutions appeared clear and nominal concentrations colorless of 1.4, 2.9, 5.7, 11, and 23 mg/L. All RExepnoeswuarlervaetses:elEsv:er2y50Mo-nmdLapyl,astWiecdbneeaskedrasycaonndtaFirniidnagy.approximately 200 mL test solution. The depth was approximately 5 cm. Number of replicates: 10 NNuummbbeerrooff tceosntceonrtgraantiisomnss:pe6rprleupsliacanteeg:ati|ve control cFeheodwinagt: 18E0a0cmh gtesTtScSh/aLm)baenrdw0a.s60femdL0o.3fmSeLleonfaYstCrTum(acampirxitcuorrenouftyuemas(t3,.5Cexro10p"hycleIl*l,s/amnLd) tornocuet. daily. sLuirgfhactei.ng:PhoCtoolpoerrtioondeof5106-flhuoourresscleignhtt,li8g-hthso.urIsntdeanrskitwyirthanage3d0-fmrionmut3e29tr-an3s8i3tiolnuxpeartitohde. water `Water chemistry of new and Dissolved oxygen range old (0 solutions 21 days): during the study: 8.38.9 mg/L (negative control exposure) 8.3-9.0mg/L (12 mg/L exposure) 8.48.9 mg/L* (48 mg/L exposure) PH 8r.a1n8g.e4(0-(2ne1gadtaiyvse)control exposure) 82-8.5 (12 mg/L exposure) Test tem8p.e4rat8u.r5e% r(a48ngmeg(/0L-e2x1podsauyrse)) 19.4-20.155C (negative control exposure) 19.4-20.10C (12 mg/L exposure) 19.4 19.50C* (48 mg/L exposure) * (Measurements discontinued at Day Element basis: Survival, reproduction and 3 due to growth. 100% mortality. Effect concentrations based on survival. Methodofcalculating mean measured concentrations: arithmetic mean RESULTS NMoemaisnuarledcocnocnecnetnrtartaitoinosn:s:Ne<gLaOtiQv,e 1c.o5n,tr2o.l9,, 51..64,,21.29,,254.,7,4811m,g2/3,L46 mg/L Element value: 21-day NOEC = 12 mg/L 21-day LOEC = 24 mg/L 2" gener2a1t-idoanyaMcuAteTCsur=viv1a7lmNg/OLEC = 12 mg/L All element values based on mean measured concentrations ALtnda.lyutsiicnaglhmieghthpoedrofloorgmya:nceAnlailqyuisdescohfrtoemsattosgolruatpihoynswwitehremapsersfsopremcetdroamtetWriilcdldiefteecItnitoenmational (sHaPmLeCa/nMdS)m.ostWhpreonmidneetnetrmpienaikngretshepocnosnecefnotrrtahteiotneostfsuthbesttaenstcesuwbasstaunsceed.inNtoheattetstemspotluwtaiosnsm,atdhee o0fqunaintaisfy son sthReempboaessiFsnoOfSin-dAitavcihdmeuna1l isomeric components. The LOQ (limit of quantitation) wr was 000121 c0o.n4c5u8rrmegn/tLlyidnutrhiinsgstsuadmy.pleThaenamlyesaisnwpraosce1d0u4r%a.l rMeecaosvuerreyodfvamlautersixoffonretiwfiscaamtpiolnessarnaanlgyezdedfrom 94 n10om1i2n1al%ovfalnueosm.inPaFl.OSMewaassusrteadblveatlhureosufgrhooumttthheeorlednseowlaultipoenrsiordas,nged from 90 to 108% of rat niasess Report FOS-tachment 1 nas 000122 Summary of analytical chemistry data: Nominal Tes. |Measured Duplicate Values at 0, 2, Concentration (11, 14, 18, and 21 Days, mg/L Respectively, mg/L. Negative |All<LOQ Control 1.78,1.72, 136,132, 1.58, 1.38, 1.56, 1.43, 1.38, 1.50, 1.47, 1.45 [Mean Measured [~~] Concentration [=e mg/L nal 107 29 3.20,3.05,3.01,3.07,275,2.77, 2:85,271,2.79,281, 281,282 57 5.97,5.87,565,5712,563,559, [56 5.36,5.39, 5.8, 5.75, 5.24, 5.37 11S, 115,116, 118,113, 11.3, 112,116,118, 116, 115, 113 2 242,23.1,240,246,228,225, [24 23.6, 23.1, 24.8, 25.0, all daphnids 104 dead after 18-days exposure 46 47.3, 48.0, 49.1, 49.4, all daphnids dead after 2-days exposure 104 sNoOlTutEi:onsM)eaannd cmoerarseusrpeodndcionngceonltdrastoiluotnisownserdeurdientgeremaicnhewdeferkoomftnheew t(erste.neDwaalys 0, 11, and 18 are "new" and days 2, 24, and 21 are "old". Biological Observations Sinurtvhiev2a4l:anAdll48sumrvgi/vLintgrefairtsmtegnetnserwaatsiosntadtiaspthincaildlsy asipgpneiafriceadntnloyrdmiaflfeartentetstfrtoermmitnhaetinoeng.atiSvuervival control group. nReeopnraotdeuscotnioDna:yD9a. phTnhiedBsoninfetrhreocnointtr-otelstansdhotwreeadtmtehantt rgerporuopdsucCt1io2n mwga/sLnosttarstiegdnipfricoadnutcliynrgeduced iinncalnuydetdreianttmheentstgatriosutipcaCl1a2namlygs/iLs o(fp t>h0e.0r5e)p.roTduhceti2o4nadnadta48dumegt/oLatsrteaatitsmteinctalglyrosuipgnsifwiecraentneoftfect on survival. 0Gr1o2wmthg:/LTwheereBonnoftersrigonniifitc-taensttlyshroewduecdedthiant cmoemapnarliesnogtnhtaontdhedrnyegwaetiigvhetcionnttrhoelt(rpea>tm0e.0n5t)groups ScoenctoronldwGaesne9r5a%t.ioSnurAvciuvtale Einxpthoesu1r.5e,:2.A9,ft5e.r6,481-2h,oaunrdso2f4emxgp/osLutrree,astumrevnitvgalroiunptshewansega10t0i,ve100, 100, 90, different and 0% respectively. Survival from the negative control (p C) in the 0.05). 24 mg/L treatment group was significantly Or niasssmReeponPROtS. Auschme1s nas 000123 `Summary of PercentMortality Mean Measured eta mg/L Jf e hf f] ] J owJw]| `Second GenerationMortality Ei R R e Toneah m--s mg/L [Exposed 48-hours f P f f w r p ] ] So 000129 ISnudmimviadruyalolfy-LEexnpgotshedanFdirDstr-yGeWneeirgahttioonfDSauprhvinviidnsg Mean Measured Concentration, [Number of [1cTM (Surviving |JH Eeqgih [orc | By Weight mg/L Daphnids | 1" =SD. m 5b, mg [NegativeCone [10 [36520111 [sb acerotis Jows ro100 fous room pop leew Jomo [ob lasso: fom: omes [2 [ewiou [ors roeet pro Reproduction MMeeaasnured mCogn/cLentration, Negative Control fNouf mber [Mean Live Total Young Surviving[1t Day of (Number of Total |g, D[Sauprhvniviidnsg |[ASdDu)lt Daphnid (+|n RP NIiemomnoabtielse | Abogrsted 1224192 9 fb s eam pop mews bo| hp] Po Bb ep mums was bo] po pole bo lo ee CONCLUSIONS tThheerteestwesurbestnaonacdevaetrsceonecfefnetcrtastoinonsu<r1v2ivmalg,/rLefporrod2u1ctdiaoyns.orDgarpohwntihoa fmaDganphaneixapomsaegdntao e2x4poasnedd48to mg/L had significantly reduced survival. rt tilAsset Spor FOS uschmen 1 wn 000125 Author and/or submitter: 3M Company, Environmental Laboratory P.0. Box 33331 St. Paul, MN 55133 DATA QUALITY Reliability: Klimisch ranking 1. REFERENCES This study Company. was conducted at Wildlife Intemational, Ltd. Easton, MD at the requestofthe 3M OTHER Last changed: 5/3/00 rh iilAsse Bor PFO -Auchan 1 wn 000126 (CRHefReOreNnIceCNToO.X80I)CITY TO THE SALTWATER MYSID TEST SUBSTANCE OIcdtenatnietsyu:lfPoenrifcluacoirdo,oc1t,a1n,e2s,u2l,f3o,n3.a4t.e4;,5m,a5,y6,a6l,s7o,b7,e8,r8e.f8e-rhreepdttaodeacsafPlFuoOrSo-,orpoFtC-a9s5s.ium(1s-alt, CAS # 2795-393) SRaemmpalreksw:asTshteorteedstusnudbesrtaanmcbeieinsta cwohnidtietipoonwsdeprri.or Staomtpeslteinwga. sPutraikteyndfertoemrm3inMedlottonbuem9b0e.r42917%. by LC/MS, 'H-HMR, "F-NMR and elemental analyses techniques. METHOD Method: OPPTS 850.1350 Type: Flow-through chronic GLP: Yes Year completed: Study completed 1999. Species: Mysidopsis bahia Report completed 2000 ASnuaplpyltiiecra:l Imno-nhiotuosreicnugl:turPeFs,OWSilmdelaisfuerIendteomnatdiaoynsal0,,Lt7d,.,14E,a2s1t,on2,8,MaDnd 35 Exposure period: 35 days cStoanttiisntgiceanlcymettahboledss:to iSduernvtiivfayltrdaetaatmweanst gervoaluupasttehdat(psrhioorwteodpaaisrtiantigsatincdalalfytseirgpnaiifriicnagn)t duisfifnegr2enXce2 g(rpo=0w.t0h5))wferroemetvhaelunaetgeadtifvoer cnoonrtmraollitgryouuspi.ngAlSlhacpoinrtoi-nWuioluks'-vsatreisatbalneddaftora h(roemporgoednuectiitoynoafnvdariance buseitnwgeeBnarttlreetatt'msetnetst.andAncaolnytsriosl omfevaanrsi.anAclelasntadtiDsutnicnaelttte'sststewsetrweepreerufsoerdmetdo euvsailnugaatepedrisffoenraelnces `cToemsptumtyesridwistahgSe:PS<S2/4P-ChoVuerrssioolnd 2.0 or at test "TOXSTAT initiation Release 3.5" statistical software. Pretreatment: None `DTielsuttCioonndwiattioenrsc:hemNaitsutrrayl (sdeuarwiantgerthdiel4ut-ewdeteok2p0e%r,iowditihmmweeldliawtaetelry,p0r.e4ce5dmimngfilttheeredt.est): Salinity: 20 (20-20) %, TOC: <10mglL aSptporcokxiamnadtetlesyt 2s4olhuotuirosn pprrieopratroautsieo. n:AfPtrerimmairxyinsgt,octkheprperpiamraerdyastt0o.c0k8s9o5lumtgio/nLwaansd pmrioxpoerdtifoonrally 0di.l0u2t2e4d,w0i.t0h11d2i,lu0t.i0on05w5a9t,erantdo p0r.e0p0a2r8e0fmigv/eLa.ddiTthioenaslixssttoocckkssowluetrieonisnjaetcctoednciennttorathteiodnisluotefr m0i.0x4i47n,g chambers (at a rate 150 mL/minute) to of 4.60 achieve mL/minute) the desired where they were mixed test concentrations. with dilution water (at a rate of SFtlaobwiltithyrooufgthherattees:t cAhpepmriocxailmsaotleultyioenlse:veEnxvtorelmuemleyasdtdaibtlieonsoftest water every 24- hours aEtxtpaochseudrteovteswsoelhso:lePsroionrotpoppoasiirtiengs,idmeys.siAdfsteprlarceeadchiinngglassesxubaelakmeartsurwiittyh, npayilrosnpmlaecsehdsicnrgeleanss DpertrindiishAsesseswmietnthRseipdoessPEoOfSnAylconhmeess1h screen attached with silicone adhesive. Both pre-pairing 3 000127 oafntdesptossto-lpuatiiorni.ng Tehxpeodseuprtehvwesasselasppwreorxeimpalatceeldy i6n.29cLmglparsisoraqtuoapraiiarifinlgleadnwdi5t.h5acpmproafxtiemraptaeilryin5g.L `Twhheictheswtacshadmibppeerds ofuotr tohafe steecsotncdhagemnbeerratfiroonmetxhpeosaupprreowpreiraete2Ltrbeeaatkmeernst wgriotuhp.1Loftest solution Numberofreplicates: four Number Number of of concentrations: six plus a fish per replicate: Fifteen negative juveniles control before pairing, pairs (10 adults) when possible after pairing. WFeaetdeirngc:heFmeidstlrivyedburriinengshtrhiemsptunaduyp:lii 3 or four times per day. Not fed the last dayof the test. Dissolved oxygen range (0- 35 days): 6.06.4 mg/L (control exposure) 59-63 mg/L (1.3 mg/L exposure) PH range (0-35 days) 8.28.4 (control exposure) Test tem8p.er3a-t8u.r4e(r1a.n3gmeg(/0L-ex3p5odsauyrse)) 2244..45--2255..12001CC ((1c.o3ntmrgo/lLexepxopsousruer)e) Methodofcalculating mean measured concentrations: arithmetic mean RESULTS MNoemaisnuarledcocnocnecnetnrtartaitioonnss:: B<kLcOonQt,rol0,.005.70,860,.102.,170,.205.,340,.505.,691,.3,1.24,.62.m7g/mLg/L Element val3u5e:-d2a0y-d(apyossiu-rpvaiivrailng()prseu-rpvaiivrailnNg)ONEOCE=C0=.505.5m5g/mLg/L 3355--ddaayy rgerporwotdhucNtOioEnCNO=E0.C25=m0g./25Lmg/L 2" generatio3n5a-cduatyerseuprrviovda&l NgOroEwCth=L0O.5E5Cm=g/0L.5(5himggh/esLt concentration tested) AAlnlaleylteimceanltmveatlhuoedsoblaosgeyd:onAnmaelaynsemseoafsutersetdsoclountcieonntsrawteiroensperformed at Wildlife Intemational (LtHdP. LuCs/iMnSg)h.igWhhpeenrfdoertmearnmcienilniqguitdhecchornocmeanttoragtriaopnhoyfwtihteh mass spectrometric test substance in the detection test solutions, the. smaamdee atondqumaonsttifpyroonmitnheenbtaspiesakofriensdpiovnisdeuaflorispeormfelruiocrcoooemtpaonneesnutlsf.onaTtheewLasOQuse(dl.imiNtoofattempt was quantitation) fortifications was 0.0.0458 mg/L in analyzed concurrently tdhuirsisntgudsya.mpTlheeamnaelaynsipsewracesnt92r.e8.coSvaemrpyolfesmactorlliexcted at pre- test ranged from 67.1110 103% of 57.4 10 99.3% of nominal. nominal. Measured values Samples at for samples test initiation had measured values from taken at test termination ranged from 59.810 90.0%of nominal Dr Iti Assent por PFOS -uschmen 1 ee we 000128 Summary of analytical chemistry data: Nominal Test| Concentratio | Measured Dupl 14, 21, 28,35, icate Days, Values at 0, Respectivel 7, y, nmgl |mgL Negative Control |All<LOQ 0.086 17 0.0694, 0.0578, 0.0478, 0.0619, 0.0606, 0.0614, 0.0554, 0.0509, 0.0515, 0.0569, 0.0580, 0.0514 0.125, 0.114, 0.0778,0.125, 0.124, 0.127, 0.0970, 0.112, 0.122, 0.128, 0.124, 0.119 0.34 0.289, 0.286, 0.231, 0.197, 0.276, 0.253, 0.227, 0.212, 0.262, 0.271, 0.278, 0.251 0.69 0.562, 0.659, 0.581, 0.450, 0.543, 0.542, 0.516, 0.528, 0.529, 0.544, 0.556, 0.583 1.23,1.32,1.13, 1.20, 1.35, 1.27, 1.23, 1.15, 1.39, 1.39, 1.26, 1.20 2.7 2.56,2.79, 2.58, 2.30, 2.54, 2.69, all mysids dead after 14-days exposure || MCoenacnenMtreaatsiuorn,ed mg/L 0.057 0.12 0.25 0.55 13 [2.6 |Percen"t""of om 7 74 93 Biological observations wSuerrveivstaalt:istAilclalsluyrsviigvniinfigcmayntsliyddsifafpepreeantrefdronmortmhael.negSautrivvievaclonitnrtolhegr1.o3upa.nd 2. 6 mg/L treatments Reproduction: The dayoffirst brood release in this study was Day 22. Dunnett's test showed that the nreegpartoidvuecctoinotnrowla(sps<ig0n.i0f5i)c.antTlhyere1d.u3caenddi2n.t6hme g0/.5L5 mg/L tre treatment atment group groups were when compa not included red to in the statistical Growth: analysisof the reproduction Mysids exposed to PFOS at data due to a statistically significant concentrations < 0.25 mg/L showed difference in survival. no statistically significant reductions in length or dry weight (p < 0.05). Second was not Generation statistically Acute Exposure: different from the Survival controls. in all PFOS treatment groups was All surviving mysids in the second > 95% and generation `exposure appeared normal with no overt signsoftoxicity. Dre tilAssRoer FsOS-achment 1 as 000129 Percent Survival Mean Measured [Juvenile |Adult Concentration, |Pre-Pairing mg/L Survival, Day 20 Post-Pairing [Survival, Day 35 Negative 78 Control pm r o Be Second Generation Survival [Mean Measured|Total Number |Concentrations, (Number |Aliveafter mg/L [Exposed [96-hours Percent Survival Negative 71 p|s Cosntrol o fn s r f] ] bs pfs fw] ere) a 000130 Adult Mysid Growth Number of canMeasured | MSuyrsviidvisn/gNumber me/L Exposed [[TMoetaalnL+enSgDt,h,mm [[DMreyanWe+igShDt,, mg - - 0.00624 Reproduction Concentration Replicate Reprod Number mg/L Days fYoung. Negative Control A 70 is B 53 14 c 70 E) D2 1 0.057 A Ig B 14 c [2 13 D 56 21 012 A 70 2 B3 2 c sa 2 D 70 18 02s A 70 1 B s6 12 c 61 2 D 56 10 OrttrAsean Nut FOS aachmert YoonSOTO peproductive Day 0257 0264 0286 0.452 0283 0200 0.186 0375 0300 0478 0.407 0257 027 0214 0344 0179 vera ea 50 00.3019525+ 02617 0.0873 0361 20.101 0003752237 wr 0001.31 [Mean Measured Numberof (Concentration, ~ Replicate Reproductive mg/L Days 0.55 x 54 B 56 c 70 D 56 13 A2 B 14 c0 D1 "Mean Numberof (UO Young/ Reproductive Day 3 0.0556 6 0.107 3 0.0429 1 0.0179 0 - 0 - 0 - 0 . oo Stal Ven = 0.0559 + 0.0376 B CONCLUSIONS There were no statistically significant effects on survival, reproduction or growthofmysid shrimp exposed to potassium perfluorooctanesulfonate at concentrations < 0.25 mg/L for 35 days. Reproduction, length and dry weight were the most sensitive biological endpoints in this study. Second generation mysids exposed to PFOS during astatic 96-hour exposure showed no adverse effects. Submitter: 3M Company, Environmental Laboratory P.0. Box 33331 St. Paul, MN 55133 DATA QUALITY Reliability: Klimisch ranking = 1 REFERENCES This study was conducted at Wildlife Intemational Ltd., Easton, MD at the request of the 3M Company. OTHER Last changed: 5/3/00 raf niasss Repos PROS. Aachmes 1 us 000132 CHRONIC TOXICITY TO EARLY LIFE STAGE OF FISH (Reference No. 84) TEST SUBSTANCE Identity: Perfluorooctanesulfonate; may also be referred to as 14C-78.02, POS or FC-95. (1Octanesulfonic acid, 1,1,2.23,3.4,4,5,5,6,6,7,7,8,8,8-heptadecafluoro-, potassium salt, CAS # 2795-39-3) Remarks: The test substance is a white powder. Sample was radiolabeled. Sample purity was not characterized The following summary is abbreviated due to the fact that this study has been superceded by a more recent test. METHOD tMheet"hPordo:poMseetdhroedcowmamsednedveedlobpieodasbsyayEpGro&cedGu,reBifoonroemgigcaannddfcrlyosstealgyesfooflflroewsedhwtahtoesre fpirsehs"e,nUt.eSd.in EPA, 1972. Type: Flow-through chronic GLP: No Year completed: 1978 Species: Pimephalespromelas RESULTS 30-Day NOEC: 1 mg/L 30-Day LOEC: 1.9 mg/L 30-Day MATC: >1 mg/L and <1.9 mg/L DATA QUALITY Reliability: Klimisch rankin=g 2. This study performed, but the analytical methodology was satisfied criteria questionable. for quality testing at the time REFERENCES This study was Massachusetts conducted at E at the requestof G & G, the 3M Bionomics, Company. Aquatic Toxicology Laboratory in Wareham, OTHER Submitter: 3M Company, Environmental Laboratory P.0. Box 33331 St. Paul, MN 55133 rr -- uw 000133 Last changed: 5/3/00 ACUTE TOXICITY TO FISH (Reference No. 86) TEST SUBSTANCE 9I4de,notirtyF:C-9P4e-rXfl.uo(r1o-oOccttaanneesusluflofnoantiec,aLciidt,hi1u,1m,2sa,l2t,;3,m3a,4y,4a,l5s.o5,b6e,6r,e7f,e7r,r8e.d8,t8oheapstPadFeOcaSflLuiosraol-t,, FC- lithium salt, CAS # 29457-72.5) Rtheemtaerstkssu:bsTteasntcesaimnpwlaetewra(satpapkreonxifmraotmel3yM24p.r5od%utcetsitosnulbostt#a1n.ceTahnedt7es5t.s5a%mwpalteeri)s.a Nmioxture of calculations sample. were made to adjust for the actual concentrationof the est substance in the test METHOD Method: Not noted. Type: Static acute GLP: No Year completed: 1994 Species: Pimephalespromelas ASnuaplpyltiiecra:lAmqounaittiocriBnigo:sysptHemasndInDc.O, FcoornttCeonltlins, CO Exposure period: 96-hours Statistical methods: LC,, values calculated by Trimmed Spearman - Karber. Test fish age: 79 days. Length and weight: Average length = 2.1 + 0.3em Average weight = 0.069 + 0.03 g Loading: 0.69g fish /L Pretreatment: None Test Conditions Dilution water: Carbon filtered well water Dilution water chemistry: pH: 84 DO: 81mg S0toyicekldanadtetsetsstasmoplluteicoonncpernetpraartaitoinono:f 4A00pmrigm/aLr.y Asltloctkesstosloultuitoinownsasweprreepmaareddeibnydidliultuitoinngwathteer appropriate amount concentration. of stock solution with dilution water to make 1 Lof solution per Stability of the test chemical solutions: Exposure vessels: 2 L glass beakers Not noted. Number of replicates: two. Number of fish per replicate: ten Number of concentrations: six plus a negative control Water chemistry during the study: [LT ---- a-- 40 0001.34 Dissolved oxygen range (-0 96 hours): 6.0-7.2 mg/L (control exposure) 4.87.9 mg/L. (56.0 mg/L exposure) PH range (0-96 hours) 8.0-8.4 (control exposure) 8.08.4 (56.0 mg/L exposure) `Test temperature range (0 96 hours) 19219.50C RESULTS Nominal Element concentrations: Bk control, 3.2, 5.6, value: 96-hour LC,= 19 mg/L (95% 10.0, C.L: 18.0, 32.0, 56.0 16-24 mg/L) mg/L Mortality of controls: None Remarks: Values reported are for concentrationof the test substance the test sample. No in the test sample. calculations were made to adjust for the CONCLUSIONS The test LC for sample fathead containing 24.5% Perfluorooctanesulfonate, minnow of 19 mg/L. Lithium salt exhibited a 96-hour Submitter: 3M Company, Environmental Laboratory P.0. Box 33331 St. Paul, MN 55133 DATA QUALITY Rdeeltiearbmiilniattyi:onKolfitmhisecthesrtansukbisntga2n.ceTchoinscesntturdayt,iwohniilnetwheelltecsotnsdoulcuttieodn,s;laacnkds daneatleyrtmiicnaaltdiaotnaoffor:the sample purity. REFERENCES This study was conducted M018, 3/25/94, by the 3M Company, Environmental Laboratory, Lab Request number OTHER Last changed: 5/2/00 Def nia ssssmens Repos PFO Atachmens 1 wa 000135 ACUTE TOXICITY (Reference No. 87) TO AQUATIC INVERTEBRATES (E.G., DAPHNIA) TEST SUBSTANCE I94d,enotritFyC:-9P4e-rXfl.uo(r1o-oOccttaanneessuullffonoantiec,acLiidt,hi1u,1m,s2a,l2t,;3m,3a,y4,a4l,s5o,5b,e6,r6e,f7e,r7r,e8d.8t,o8-ahsepPtFadOeScafLliusoarlot-,,FClithium salt, CAS # 20457-72-5) sRuebmsatraknsc:e anTdhe75te.s5t%sawamtpelr)e.isNaomicxatlcuurleatoifotnhsewteerstesmuabsdteantcoeadijnuwsattfeorr(tahpeparcotxuiamlactoenlcyen2t4r.a5ti%ontesotf the test substance in the test sample. METHOD Method: Not noted. Test type: Static acute GLP: No Year completed: 1994 Species: Daphnia magna Analytical monitoring: pH and DO content Statistical methods: Test daphnid source: OEbCt,a,ivnaelduefsrocamlUc.uSl.atEedPAus-iNngETTArCim,mDeudluStphe,aMrimnanne-sKoatraber method `Test daphnid age at study initiation: <24-hours Test Conditions Dilution water: Carbon-filtered well water Dilution water chemistry: pH: 8.4 DO: 86 mg/L 0Stoyicekldanadtetsetsstasmoplluteicoonnscpenrterpaatriaotnioonf:10A00prmigm/aLr.y sAtlolctkesstolsuotliuotniownassweprreepmaareddeibnydidliultuitoinngwattheer appropriate amountof concentration. stock solution with dilution water to make 50 mLof solution per Exposure vessels: 100 Number of replicates: mL 4 glass beakers containing 50 mL of est solution. Numberof daphnids per replicate: 5 NWautmebrerchoefmicsotncreyndturartiinognst:hefsitvuedpyl:us a negative control Dissolved oxygen at test termination: 7.0 mg/L (control exposure) pH 7a.t8tmesgt/tLer(mi1n0a0t0imong:/L exposure) 8.6 (control exposure) 8.6 (1000 mg/L exposure) Test temperature range (0 48 hours) 20.1-21.00C E-- lement basi-- s: mortality a-- nd immobilization a 000136 RESULTS Nominal Element vcaolnuce:entrat2i4o-nhso:urBEk Ccon,=tro3l3,01(0209,0-13807,0)32m0g,/5L60, 1000 mg/L 48-hour EC,= 210 (190-230) mg/L 48-hour NOEC = 100 mg/L StthaetTisrtiicmamleEdvaSlpueaatrimona:n-KTahrebeErCmSe0thvaolduewsitahndtr9im5%setcotonf0i%d.ence intervals were calculated using Mortality of controls: None Remarks: Values reported are for concentrationof the test substance the test sample. No in the test sample. calculations were made to adjust for the CONCLUSIONS The test EC for sample containing 24.5% Perfluorooctanesulfonate, Daphnia magna of210 mg/L. Lithium salt exhibited a 48-hour Submitter: 3M Company, Environmental Laboratory P.0. Box 33331 St. Paul, MN 55133 DATA QUALITY Rdeeltiearbmiilniattyi:onKloifmtihsecthesrtasnukbisntga2n.ceTchoinscesntturdayt,iwohniilnetwheelltecsotnsdoulcuttieodn,s;laacnkds daneatleyrtmiicnaaltdiaotnoa ffort:he sample purity. REFERENCES This study was conducted MI018, 2/10/94. by the 3M Company, Environmental Laboratory, Lab Request number OTHER Last changed: 5/2/00 Dra ninsessReportPFOS-tachment 1 wo 000137 ACUTE TOXICITY TO FISH (Reference No. 90) TEST SUBSTANCE Identity: 99, or 3M SPaemrfpllueorNooo.ct2a.nc(s1u-lOfcotnaantee,suDlfEonAicsaaltc;idm,a1y,1a,l2s,o2,b3e,3r,e4f,e4r,5r,e5d,t6o,6a,s7,P7,R8O.8S.8D- EA salt, FC- hReepmtaardkesca:fluToersot-,sacmopmlped.iswaimtihx2t,u2r-eiomifntohbeistfe{settshuanboslt]an(c1e:1i)n, wCaAtSer#(a7p0p2r2o5x-i1m4a-t8e)ly 25% test s10ubasdtjaunstcefoarndth7e 5ac%tuwaaltecro)n.cenAltlravtailounoesfrtehpeortteesdt sreulbastteatnocethiins tmhiexttuerset.samNpolec.alculations were made METHOD Method: Environmental Protection April, 1975. Standard Methods. Agency, Ecological Research Series EPA-660/3-75-009, Type: Static acute GLP: Yes Year completed: 1979 Species: Lepomis macrochirus SAunpapllyiteirc:alOmsoangietoCraitnfgis:hepriHesa,nIdncD. iOn/OasmamgoenBieaaccho,ntMeinstsouri. Exposure period: 96-hours Statistical methods: Probit analysis. Test fish age: Not noted. Length and weight: Average length = 28.6 + 2.17 mm. Average weight = 0.60 + 0.15 Loading: 0.2 g fish /L Pretreatment: None `Test Conditions Dilution water: Laboratory well water Dilution water chemistry: Dissolved oxygen: 9.3 mg/L Hardness: 255 mg/L as CaCO, Alkalinity: 368 mg/L as CaCO3 pH: 78 Conductivity: 50 Omhos/em Scotnoccekntarnadtitoenstofso1l5u0timogn/pmrLe.parTahteiotens:t cPornicmeanrtyrasttioocnks pwreerpearperdepianrdeedibonyitzreadnswfaetrerrinagtaappropriate afloiaqmuowtshoefnthsteirsrtioncgkinsttaonxdiacradntdailrieqcutoltys.to Ttehsettecsotncchenatmrbaetriso.nsTwheeretesptrespoalurteidonbsasweedroennototteadl to sample, not on percent concentrationof Concentrations dosing rate: Once the test substance in the test sample. SEtxapboilsiutryeofvetshseeltse:st4c0heltmcircagllasssolauqtuiaornisa:coNnottainnoitnegd30Lof test solution. raf nia sscssmen Repos PROS. tachment 1 ae 000138 Number of replicates: one Number of fish per replicate: ten Number of concentrations: six plus a negative control `Water chemistry during the study: Dissolved oxygen range (0 --96 hours): 6.0- 8.4 mg/L (control exposure) 5.8-83 mg/L (18 mg/L exposure) 82-83 (control exposure) 8.3-8.3 (18 mg/L exposure) "Test temperature: Temperature held constant at 220C through use ofa water bath for test vessels. RESULTS Nominal concentrations: Bk control, 18, 37, 75, 160, 320, 650 mg/L Element value: 24-hour LCy, = 460 (370-580) mg/L. 48-hour LC, = 370 (290-470) mg/L. 96-hour LC,= 31 (22-43) mg/L. 96-hour NOEC = 18 mg/L (C.L. not calculated) All element values based on nominal concentrations Statistical evaluation of mortality: Probit analysis was used to calculate LC, values and the corresponding confidence limits. Quality Check for Test Organism Health: 9T6h-ehboluuregLilCl,saunnfdis9h5w%erceoncfhiadlelnecnegeldimwitisth(Car1e)fewreernecewictohminpotuhned9,5A%ntcionmfyicdienncAe. The observed limits reported in the literature, indicating that the fish were in good condition. Cumulative percent mortality: Nominal TmesetlConcentration 48-hours 72-hours wo fo fw]| fo o fo o Jf w Jw fm Jorfw Joo] 000139 CONCLUSIONS c`Tohnefitedsetnscaemipnlteerv9a6l-ohfou2r2-L4C3,mog/rL.blueTghiell9s6u-nhfoiusrh nwoasobdseetrevremdineeffdectto cboen3c1entmrga/tLiowniwtahs2 1985m%g/L. Submitter: 3M Company, Environmental Laboratory P.O. Box 33331 St. Paul, MN 55133 DATA QUALITY dReeltiearbmiilnitayt:ionKloifmtihsecthesrtasnukbisntga2n.ce Tchoinscesntturdayt,iwohniilnetwheelltecsotnsdoulcutteidon,slaacnkdsdaentaelrymtiicnaaltidoantoaf tfohr e sample purity. There were the concentrations at given also gaps in the time intervals. measurementofwater quality criteria fora number of REFERENCES This study was conducted by Analytical on behoaflthfe 3M Company. BioCheistry Laboratories, Inc. of Columbia, Missouri OTHER Last changed: 5/2/00 Dr IkiAssessment per PFOS sche 1 I 000140 ACUTE TOXICITY (Reference No. 93) TO AQUATIC INVERTEBRATES (E.G., DAPHNIA) TEST SUBSTANCE Imdiexnetditpyr:odPuecrtflFuoMr-o3o8ct2a0ne(ssuelefoRneamtaer;ksm)a. y (a1l-sOocbteanreesfuelrfroenditco aacsidP,F1O,S1,2o.r23F.C3-,94,54,o5r,5a,s6p,a6r,t7,o7f,8t,h8e.8- heptadecafluoro-, potassium salt, CAS # 2795-39-3) Retehemraarnkds:waTtheer (taesptprsoaxmipmlaeteislyFM2-43-82280%,taesmtisxutbusrteanocfetihne dteisetthsyulbesnteangcleycionldbiuettyhlyeltehneer galnycdol butyl wteastters)u.bsCtaalnccuela(t2i8on%s)wienrtehematedstestaomapdljeusatntdesntovaaldujeusstumseinntgwtahesumpapdeer lfiomritthceonpcreensternacteioonfotfhethe diethylene glycol butyl toxicity was due to the ether or water when noted below. These presenceofthe Perfluorooctanesulfonate calculations substance. assumed that all METHOD Method: OECD 202 Test type: Static acute GLP: Yes Year completed: 1991 Species: Daphnia magna AStnaatliysttiiccaallmmeotnhiotdosr:ingE:C,,DOv,alpuHes, cCaolncduulcattievd,itwyh,eanndpotsesmipbelreabtuyrsetwanedraerdmosntaittiostriecdaldatielcyh.niques (Stephan, 1983) `Test daphnid Analysts, Inc., source: Obtained Hampton, NH. from cultures maintained by EnviroSystems Division, Resource Test daphnid age at study initiation: Test Conditions < 24-hours Dilution Dilution water: Well water water chemistry: from wells at EnviroSystems in Hampton, New Hampshire. pH: 78% Conductivity: 1200 umhos/cm* TOC: <20mg/L * Values measured at time of test. Lighting: Cool white fluorescent lights, hours dark. No transition period noted. intensity 23 uE/s/m'. Photoperiod of 16-hours light, 8- Satto1c0k00anmgd/tLe.st Tsohleutpiroinmsarpyresptaorcaktiwoans:prAopoprrtiimoanrayllsytodciklustoeldutwiiotnhwdailsutpiroenpwaarteedrintodiplruetpiaornewtahteer five test concentrations. Edexpptohosufrteesvtesssoellust:io2n5w0amsL6 cpml.astic beakers containing 200 mLof test solution. The approximate Numberofreplicates: Four Number of daphnids per replicate: Five `NWuamtebrecrhoefmicsotnrceyndturartiinognst:heFsitvuedyp:lus a negative control raf nial scones Report PROS. tachment 1 wa 000141 Dissolved oxygen range(0 -- 48 hours): 8.2 -8.5 mg/L (control exposure) 8.18.5 mg/L (150 mg/L exposure) PH range (0 - 48 hours) 7.88.6 (control exposure) 7.88.6 (150 mg/L exposure) Test temperature range (0 - 48 hours) 20.8-21.00C (control exposure) 20.7-20.9CC (150 mg/L exposure) Conductivity range (0 - 48 hours) 1200 - 1300 umhos/em (control exposure) 1200 -- 1300 umhos/cm (150 mg/L exposure) [Element basis: mortality RESULTS Nominal Element concentrations: Bk control, values: 24-hour EC,= 25, 40, 60, >150 mg/L 100, (C.L 150 not mg/L calculable) 48-hour ECy, = 49 (43-56) mg/L 24rhour EC, 42 mal. Perfluorooctanesulfonate concentration adjusted element value: 48-hour EC,, = 14 mg/L. Cumulative percent mrtaity: All element values based Biological observations: on nominal concentrations Ninety five percent survival occurred in the control exposure. The numberofsurviving organisms and the occurrenceofsublethal effects and immobilization or other sublethal effects were determined visually and recorded initially and after 24 and 48 hours. Nominal Test Concentration |24-hours mg/L [48-hours Neg Conwol Jo [5 | f BE oe [fo fo [o so w| Control response: Satisfactory p15 pt as 000142 CONCLUSIONS c`Tohnefitdesetnscuebisnttaenrcvael4of84-h3o-u5r6EmCg,/Lf.orIDfaypohunaisasmuamegnalal wtaoxsicdiettyoerfmtihneedmitxotbuere49ismdgu/eLtwoitthhe a 95% Perfluorooctanesulfonate, the adjusted 48-hour EC,, value is 14 mg/L (49 mg/L X 0.28). Submitter: 3M Company, Environmental Laboratory, P.O. Box 33331 St. Paul, Minnesota 55133 DATA QUALITY cRoenlicaebnitlriattyi:onKsliinmithsechtersatnskoilnugti=on2s. aTndhesasmtpuldye lpaucrkistyanisalnyotticsaulffmiecaiesnutrleymcehnartaocftetreiszteds.ubstance PAedrdfiltiuoonraololcyt,andcaetsaulisfofnoartaemaisxtthuerediaentdhytloexniecigtlyyccaolnnbouttybleeptohseirticvoeullydaatltsroibcuotnetdrtiobute to the toxicity. were not The basic water quality parameters included in the final report. (hardness, alkalinity and calcium/magnesium ratio) REFERENCES HThaimsptsotund,yNwHasatcotnhdeurcetqeudesattofEtnvhiero3SMysCtoemmpsaDniyv.ision, Resource Analysts, Incorporated, OTHER Last changed: 5/3/00 CL ------------ nao 000143 ACUTE TOXICITY TO FISH (Reference No. 184) TEST SUBSTANCE Identity: Perfluorooctanesulfonate, Ammonium salt; `may also be referred to as PFOS NH," salt or FC-93. (1-Octanesulfonic acid, 1,1.2.2,3,3,4,4,5,5,6,6,7,7,8,8,8-heptadecafluoro-, ammonium salt, CAS # 29081-56-9) Remarks: Test sample was taken from 3M production lot #1. The test sample is a mixture of the No test substance in isopropanol and calculations were made to adjust water (25% test substance, 20% isopropanol, 55% for the actual concentrationof the test substance in water). the test sample. METHOD Method: Not noted. GTyLpPe:: NoStatic acute Year completed: 1974 Species: Pimephales promelas Supplier: Not noted. Analytical monitoring: pH and DO content Exposure period: 96-hours Statistical methods: Plotted LC,, Test fish age: Not noted. Length and weight: Average length =2 inches, Average weight = 1.5 g Loading: Not noted. Pretreatment: Not noted "Test Conditions Dilution water: carbon filtered city of St. Paul, MN water Dilution water chemistry: Not noted. Stock and test solution preparation: Not noted. Concentrations dosing rate: Once Stability of the test chemical solutions: Not noted. Exposure vessels: Not noted. Number of replicates: One. Number of concentrations: five plus a `negative control Water chemistry during the study: Dissolved oxygen range (0 - 96 hours): 5.0-5.9 mg/L (control exposure) 4.2-5.0 mg/L (100 mg/L exposure) PH range (0 - 96 hours) 7.0-7.1 (control exposure) 7.0-7.1 (100 mg/L exposure) `Test temperature range (0 - 96 hours) 21-220C (70-720F) ot 000144 RESULTS Nominal concentrations: Bk control, 10, 25, 50, 75, 100 mg/L Element value: 96-hour LCy,= Mortality of controls: None 85 mg/L (CL not determined) wRaesmacroknsd:uct9e5d%oncotnhfeimdiexntcuerleoimfitsthweetreestnsoutbcsatlacnucleatiend2f0or%thiissopmraoteprainaoll. aAndddi5t5io%nawlaltye,r.teTsthieng dveatleuremrienpeorttheediampppalcitcosftoththeatprmeisxetnucreeofantdhenootrgtahneitcesstosluvbesnttaonrcew.haNtopoartttieomnpotfwathsemtoaxdiecittoy can be contributed to the Perfluorooctanesulfonate, ammonium sal. CONCLUSIONS `LTChe,tfeosrt sfaatmhpelaed cmoinntnaionwionfg8255%mgPe/rLfluorooctanesulfonate, ammonium salt exhibited a 96-hour Submitter: 3M Company, Environmental Laboratory P.O. Box 33331 St. Paul, MN 55133 DATA QUALITY Reliability: Klimisch ranking 3. REFERENCES `This study was conducted by the 3M Company, Environmental Laboratory, 7/29/74 to 8/2/74. OTHER Last changed: 5/3/00 raf nisAsssnens Repos PFOS -Atachmen 1 1000145 ACUTE TOXICITY TO FISH (Reference No. 185) TEST SUBSTANCE Identity: or FC-93. P(e1r-fOlcutoarnoeoscutlafnoesnuilcfaocniadt,e,1,A1,m2m,2o,n3,i3u,4m,4s,a5l,t;5,m6,a6y,7a,l7s.o8,b8e,8r-ehfeeprtraeddectaoflausorPoF-,OSamNmHo,n'isualmt salt, CAS # 29081-56-9) tRheematersktss:ubsTteasntcesaimnpilseopwraospatnaokleannfdrowmat3erM(p2r5o%dutcetsitosnublsotta#n1c.e,T2h0e%tesitsosparmopplaenoils,a5m5i%xtwuarteero)f. No calculations sample. were made to adjust for the actual concentration of the test substance in the test METHOD Method: Not noted. Type: Static acute GLP: No Year completed: 1974 Species: Pimephales promelas Supplier: Not noted. Analytical monitoring: pH and DO content Exposure period: 96-hours Statistical methods: Plotted LC, Test fish age: Not noted. Length and weight: Loading: Not noted. Average length =2 inches, Average weight = 1.5 g Pretreatment: Not noted Test Conditions Dilution water: Carbon filtered city ofSt. Paul, MN water Dilution water chemistry: Not noted. Stock and test solution preparation: Not noted. Concentrations dosing rate: Once Stability of the test chemical Exposure vessels: Not noted. solutions: Not noted. Number of replicates: One. Number of concentrations: five plus a negative control `Water chemistry during the study: Dissolved oxygen range (0-96 hours): 4.5-5.7 mg/L (control exposure) 3.8-5.0mg/L. (125 mg/L exposure) PH Not recorded at highest range (0-96 hours) conc. (150 mg/L) due to 100% mortality. 7.0-7.0 (control exposure) 7.0-7.0 (125 mg/L exposure) rf nia NssostsmreenscoRerpdoesdPaFtSh-igthaecshtmecnotn1c. (150 mg/L) due to 100% mortality. sa 000126 `Test temperature range (0 -- 96 hours) 20-210C (69-700F) RESULTS NEloemmiennatlvcaolnucee:ntr9a6t-ihoonusr:LCB;k,=con1t0r0olm,g5/0L, (75C,L.10n0o,t 1d2e5t,er1m5i0nemdg)/L Mortalityof controls: None wRaesmacroknsd:uct9e5d%oncotnhfeimdiexntcuerleiomfittshweetreestnsoutbcsatlacnucleatiend2f0or%tihissopmratoeprainaol.l aAndddi5t5io%nawlaltye,r.teTsthieng value reported determine the iampppalcitesotfotthheatprmeisxetnucreeofatnhdenootrgtahneitcesstosluvbesnttaonrcew.haNtopoartttieomnpotfwtahes made to toxicity can be contributed to the Perfluorooctanesulfonate, ammonium salt. CONCLUSIONS TLhCe,tfeosrt sfaatmhpelaed cmoinntnaionwinogf2150%0 mPger/fLluorooctanesulfonate, ammonium salt exhibited a 96-hour Submitter: 3M Company, Environmental Laboratory P.0. Box 33331 St. Paul, MN 55133 DATA QUALITY Reliability: Klimisch ranking 3. REFERENCES `This study 1019/74. was conducted by the 3M Company, Environmental Laboratory, 10/15/74 to OTHER Last changed: 5/3/00 Cr -- ws 000147 ACUTE TOXICITY TO FISH (Reference No. 503) TEST SUBSTANCE Identity: Perfluorooctylsulfonate, Fluoroalkyl ammonium derivative. d[i1d-eDceycladmiimneituhmy,lNa-mdmeocnyilu-mN.sNal-td;immeatyhyall-so, be referred salt with to as 1,1,2,2,3,3,4,4,5,5,6,6,7,7.8,8,8-heptadecafluoro--octanesulfonic acid (1:1), CAS # 251099-16- 8] Remarks: The 3M production [ot the test laboratory as P3025. The number was Lot 1. sample was labeled The test sample F-11615, Lot 1. is L-14394 referred to The test sample is a by m0i-x5t%uroeforfetshieduatlesptesrufblsutoarnoccheeimnicwaaltse)r.(Aalplprvoaxliumeastreelpyo3rt0e-d4r0e%latteesttosutbhisstamnicxet,ur6e.0-7T0h%e tweastters,amapnlde a`gaiptpaetairosn.to Nbeoaca2l-cpuhlaasteiodnisswpeerrseiomna(dceletaoraldijquusitd fwoirththoepaacqtuuaelscoolindc)enwthriacthiornaopfitdhlyesteepsatrsautbesstaafntceer in the test sample, METHOD Method: OECD 203 Type: Static acute GLP: No Year completed: 1996 Species: Pimephales promelas Supplier: Not noted. Analytical monitoring: DO, Exposure period: 96-hours pH, temperature, and conductivity were monitored daily. NStOatEisLtiwcaalsmceatlhcuoldast:ed LusLi,ngvaFliusheesrc'aslcEuxlaacttedtesutss.ing the Trimmed Spearman-Karber method. The Test fish age: Not given. Length and weight: Loading: 0.26 g/L Average length = 11.3 mm, Average weight = 7.8 mg. Pretreatment: None Test Conditions pDriilourtitoonusweatienr:theDteecsth.lorinated City of Duluth, MN tap water. Water was aerated for 24-hours Dilution water chemistry: Hardness: 48 mg/L as CaCO, pH: 8.08 Lighting: Cool-white fluorescent bulbs. transition period noted. Photoperiodof 16-hours light, 8-hours dark used. No pSrteopcakreadndintdeisvtidsuoallultyiofnorperaecphartaesttiorenp:licWaatteecronaccecnotmramtoidoantbeydmfarsacstiaodndsi.tTieosnot fsvoilugtoiroonusswleyrsehaken (tevsotrtseuxbs1t/a2ntcoe 1i/n34sLooluftdiiolnudteipothn).watTerh.e aTqhueeosoulsutpihoanssewwearse sviipgohroonuesdlyfrsotmirrtehde fvoerss2e1l-hatoumrisd- depth. rf ni sscssmen ReposPFO Aachen 1 nse 000148 ee Concentrations dosing rate: Once Stability of the test chemical solutions: Not noted. `ETxepfloosnu-rlienevdeslsiedlss:fit4te-dLwgiltahssstjaorpspecrosnttaoiancincgom3m-oLdoaftteesotxsyolguetniofn.lusThhinegojafrshweeadrsepsaecael.ed with Number of replicates: two Number of fish per replicate: ten N`Wuamtbererchoefmciosntcreyntdruartiinognst:hethsrteuedyp:lus a negative control Dissolved oxygen range: (0-96 hours): 9.1 - 14.6 mg/L (control exposure) PH 8ra7ng1e8: .2(0m-g9/6Lho(u7r0s0)mg/L exposure) 7.80 7.78 8.08 -7.99 (control exposure) (700 mg/L exposure) Test temperature range (0 - 96 hours) 208-209C Conductivity range (0-96 hours) 128 - 142 118-154 Omhos/em Ombos/em (control exposure) (700 mg/L exposure) oRbesmearrvaktsi:onOpexryigode.n wTahse addisdseodlvteodthoexyhgeaednscpoancceenitnrtahteiojanrsswbeerfeorseupsecra-lsiantguirnaitteidalilny athnedtaetsteach vessels, particularly in the 700 mg/L exposure concentration. RESULTS Nominal Element loading concentrations: Bk control, 400, 700, value: 24-hour LL, = 618 (568 - 673) mg/L 1,000 mg/L. 48-hour LL, = 607 (554 - 664) mg/L 72-hour LLy, = 595 (551 - 643) mg/L. 96-hour LLy,= 562 (523 -604) mg/L 96-hour NOEL = <490 mg/L All element values based Biological observations on nominal concentrations. after 96-hours: No mortality or abnormal behavior observed in the ncoengcaetnitvreatcioonntsr.ol Sduurrfiancgitnhgewtaesst. obMsoerrtvaelditiyn whasaooflbtshefrevefidshinatthtehere7m0a0inmign/gLeexxppoossuurree coobnsceernvterdatiinotnheat42040-hmogur/sL,eaxnpdos2ufrieshcownecreentqruaiteisonc.ent at 96-hours. No abnormal behavior was Or iisssmReeportnPOtS Anschme1t ss 000149 Cumulative percent mortality: Nominal LCoonacdeinntgraTteisotn,1,urs [48-hour|72-hours mNge/sLGomt Jo TJo oJo] fmooo s Ts on es nfs]] Lowest concentration causing 100% mortality: 1,000 mg/L Mortality of controls: None Remarks: Values reported are for the test sample. No calculations were made to adjust for the concentration ofthe test substance in the test sample. CONCLUSIONS mg/L. `The test sample 96-hour LL, for fathead minnow was determined to be 562 mg/L with a 95% confidence interval of 523 ~604 mg/L.. The 96-hour no observed effects level (NOEL) was <490 Submitter: 3M Company, Environmental Laboratory, P.O. Box 3333. 1, St. Paul, Minnesota, 55133 DATA QUALITY cRoenlicaebnitlriattyi:onKsliinmtihsechterstanskoilnutgi2o.nsTahnedsstaumdpylleapcukrsiatnyaliystnioctalsumfefaicsiuerntelmyecnhtaroafctteesrtiszeudb.stance Additionally, data is for a mixture and toxicity cannot be positively attributed to didecyldimethylammonium Perfluorooctyflonsautel salt alone. Also, supersaturation ofthe test solutions with oxygen could also have contributed to thetoxicity. REFERENCES `This study was conducted at AScl Corporation, Environmental Testing Division, Duluth, MN, at the request ofthe 3M Company. OTHER Last changed: 5/24/00 Dr ttacmaatPOS.cn ee wy000150 ACUTE TOXICITY (Reference No. 504) TO AQUATIC INVERTEBRATES (E.G, DAPHNIA) TEST SUBSTANCE FIlduenotriotayl:kylPearmflmuoonroiouctmyldseurilvfaotniavtee., d(i1d-eDceycladmiinmieutmh,ylNa-mdmeocnyli-uNm,sNa-ldt;immeatyhyall-s,osbaeltrweifterhred to as 1,1:2,2,3,3,4,4,5,5,6,6,7.7.8,8,8-heptadecafluoro-1-octanesulfonic acid (1:1), CAS # 251099-16- 8Remarks: The 3M production lot number was Lot 1. The test sample is L-14394 referred to by the test laboratory mixtureofthe test as P3025. substance The sample was labeled in water (approximately F-11615, Lot 1. The test sample is a 30-40% test substance, 60-70% water, and 0ap-p5e%aorfsrteosbieduaal2-ppehrafsleuodrioscpheermsiicoanls()c.leaArlllivquailduewsitrhepooprateqdueresloaltied)towthhiicshmirxatpuirdel.y sTehpeartaetsetssaafmteprle aingitthaetitoens.t sNaomplcael.culations were made to adjust for the actual concentration ofthe test substance. METHOD Method: OECD 202 Test type: Static acute: GLP: No Year Completed: 1996 Species: Daphnia magna SAtnaatliysttiiccaallmmeotnhiotdosri:nEg:L,DOv,alpueHs, ctaelmcpuelraatteudruesainngd TcornidmumcteidviStpyewaerrmeanm-oKnairtboerredmedatihloy.d. NOEL value calculated using Test daphnid source: Steel's Many-One Ran Obtained from cultures test. maintained by AScl Corporation, Duluth, MN. `Test daphnid age Test Conditions: at study initiation: <24-hours pDriilourtitoonusweatienr:theDteecsth.lorinated City of Duluth, MN tap water. Water was aerated for 24-hours Dilution water chemistry: Hardness: 44 mg/L as CaCO, pH: 8.04 Lighting: Cool-white fluorescent bulbs. transition period noted. Photoperiod of 16-hours light, 8-hours dark. No pSrteopcakreadndintdeisvtidsuoallultyiofnosr cparcehpacroantcieontnr:atWiaotnebry-amcacsosmamdoddiatitoendoffravcitgioornos.usTleystshsaokleutnitoensstwere substance in I 10 1/3 solution Lofdilution depth). The water. The solutions were vigorously aqueous phase was siphoned from the stirred vessel for 23-hours at mid-depth (vortex after 1/2 seutling for 1-hour. sEoxlpuotisounrseweverseseKlesp:t2c5o0vemrLedbdourorsiinlgictahteeegslt.ass beakers containing 200 mLoftest solution. The Number of replicates: Four rNauhmbtielrAosfsdeanpthRnoidrsPEpOer rAeupaclhimceantse1: Five sr 000151 WNautmebrerchoefmciosntcreyntdruartiinognst:hefsivteudpyl:us 2 negative control Dissolved oxygen range (0 -- 48 hours): 8.69.1 mg/L. (control exposure) PH 8ra0n-ge8(80-mg4/8Lho(u5r0s)mg/L exposure) 8.04-8.11 (control exposure) `Test tem7pe.r9a2t-u8r.e00ra(n5g0em(g0/L4e8xhpoousrusr)e) 209-21.0C Conductivity range (0 - 48 hours). 142-155 Smhosem (control exposure) Eleme1n2t0-ba1s2is4: Ommorhtoasli/teyman(d50immmgo/biLleizxaptoisounre) RESULTS Nominal Element loading concentrations: Bk control, 3.13, 6.25, value: 24-hour EL,, = 27.0 (18.7-39.0) mg/L 12.5, 25, 50 mg/L 48-hour EL, = 11.3 (9.6-13.2) mg/L 48-hour NOEL= 6.25 mg/L All element values based on nominal concentrations. `StTartiimsmtiecdalSpEevaalrumaatni-oKna:rbTehremEeLth,odv.aluTehseaNndO9E5L%wcaosnfciadlceunlcaeteidntuesrivanlgsSwteeerle'scaMlacunlya-teOdnbeyRtahnek BteisotluogsiicnagltohebsTerOvXatSiTonAs:T sDtaatpihsntiicdalssionftthwearneegVaetrisvieocnon3t.r2o,lU,nainvdertshiety3.o1f3Waynodm6i.n2g5.mg/L otvreerattmcelnitniscaalppseiagrnseodfhteoaxlitchiytya.ndTnhoeremfaflectthsrnooutgehdouitn tthhiestsesttudwyitwherneo mmoorrttaalliittyy;, inmomiombmiolbiitlyizoartion vwiassuanloltyeadnadtraencyortdesetdcionnicteianltlryaatinodn.aftTehre24nuamnbde4r8ohfosurusr.viving organisms were determined Dra itlAsses Ror FOS uschmens 1 ss 000152 Cumulative percent mortality: Nominal Loading Test |Concentration mg/L 24-hours |48-hours ff h i o h s] ] [F 2 o Jw] Control response: satisfactory Remarks: Values reported are for the test sample. No calculations were made to adjust for the concentrationofthe test substance in the test sample. CONCLUSIONS `The test substance 48-hour EL50 for `Daphnia magna was determined to be 11.3 mg/L with a 95% confidence interval of9.6-13.2 mg/L. 6.25 mg/L. The 48-hour no observed effect level (NOEL) was Submitter: 3M Company, Environmental Laboratory P.O. Box 33331 St. Paul, MN, 55133 DATA QUALITY `Rceolnicaebnitlriattyi:onKsliinmtihsechterstanskoilnugti2o.nsTahned sstaumdpylleacpkusriatnyaliystnioctalsumfefaisciuernetlmyenchtaorfatcteesrtizseudb.stance Additionally, data is foar mixture and toxicity cannot be positively attributed to didecyldimethylammonium Perfluorooctylsulfonate salt alone. REFERENCES This study was conducted at AScl the requestofthe 3M Company. Corporation, Environmental Testing Division, Duluth, MN, at OTHER Last changed: 5/24/00 000153 APPENDIX II AQUATIC EXPOSURE DATA (MULTI-CITY STUDY) CONTENTS Analytical reports for water column samples from the following cities: Cleveland, TN Decatur, AL Mobile, AL Pensacola, FL Columbus, GA Port St. Lucie,FL. -- Dra itl AsseRepsortPOS Append 1 oo a 000154 Analytical Report Fluorochemical Characterization of Surface Water Samples Cleveland, Tennessee (W1973) Centre Analytical Laboratory Report No. 023-014A ------------rr-- esm-- e------ -- Testing Laboratory Centre Analytical Laboratory, Inc. 3048 Research Drive State College, PA 16801 -------- ee-- e -- ~em-- esmee ---- e 3M Environmental Laboratory Contact Kent R. Lindstrom Bldg. 2-36-09 SL PaPu.lO,. MBNox5353133331-3331 Phone: (651) 778-5352 cr e ---------- Requester Kris J. Hansen, Ph.D. 3M Environmental Technology & Safety Services Bldg. 2-3E-09 P.O. Box 33331 St. Paul, MN 55133-3331 Introduction Results are reported for the analyosfias seriesof surface water samples received by Centre Analytical Laboratories, Inc. (Centre) from the 3M Environmental Laboratory. The samples were collected from Cleveland, Tennessee. The Centre study number assigned to the project is 023-014. Specific fluorochemical characterization by liquid chromatography /tandem mass spectrometry (LC/MS/MS) was requested for all samples. A total of8 samples were received for analysis. The samples were prepared and analyzed by LC/MS/MS for the following list of fluorochemicals: [TT -- ~ ns000155 Table I: Target Analysis [CC CompoundName [7] [ Perfluor Sulo fonao ste| ct_ an | e C P [e Prefrlfulou ro cSuo rlfoc o nyt lo ama ic den | | tc_ aa_ n t| e e| `The analytical method results are on file with used here was validated Centre. Data presented by Centre. here is the The validation protocol and highest quality data available at this time. Sample Receipt `iTnhdeivsiadmupallessamwpelree csounbtmaiitnteerds winerinedirveciediuvaeld.plaSstaimcpcloenstawienreersraencediwveedreonno0t5/p0r3e/s0e0r.vedT.heEisgahmtple collection dates were not supplied. Chain-of-custody information is presented in Attachment A. Sample Hansen MC-102H was on 5/16/00). not analyzed as per client request. (E-mail communication from Kris Holding Times sTthabeilaintayloyfttichael maneatlhyotdesoufseidntwearessvtafloirdaltoendgeargapienrsitoadsmhaaxsinmoutmbeheonlddientgertmiimneedo.f 14 days. The Methods-Analytical and Preparatory 41 LOMSMS 4.11 Sample Preparation for LC/MS/MS Analysis rSeammpolveesrweseirdeuailnicthilaolrliynet.reaStoeldidwipthhas2e00exutLraocfti2o5n0(SmPgE/)Lwsaosduisuemdtthoiopsruelpfaatree stohleutsiaomnplteos cfaorrtrLiCdg/eM.ST/hMeScaanratlryisdigse. waAsffoirrtsyt-emliultleidltweirtphor5timoLn ooff4sa0m%plmeewthaasntorlanisnfwerarteedrtsoolautCi,o,n.SPE mTlhepoerltuiaotne owfasmedtihsacnaorldewdaasndcotlhleecStPedEfcoorlaunamlnyswiassbtyhLenC/elMuSt/edMSwi.thTh1i0s0t%remaettmheanntolre.suAlte5d in an eight-fold concentrationof the samples prior to analysis. 4.12 Sample Analysis by LC/MS/MS cInhrHoPmLatCo,graanpahliicqucootloufmne.xtrBaacsteids ionnjetchteedafafninditpyaosfstehdetharnoaulgytheafloriqtuhied-spthaatsieonary phase in `tahemocuonltoumfntirmeel.atiFveoltlootwhiengliqHuPidLmCobseiplaerapthiaosne,,EtShe/ManSalpyrtoeviisdersetaairnaepdidfoarnadcahcacruarctaetreistic of nia Asscssmen Repos PFO - Append 1 wa 000156 mEleeacntsrofsoprraaynailsygzeinnegraalwlyidoeperraantgeedoaft orrelgaatniivcelcyommiploduntedmsp,eriantculruedsi;ngmoflleucourolcehsemairecailosn.ized, fragmented, and detected. Tons quantitated against standards. characteristicofknown fluorochemicals arc observed and A Hewlett-Packard HP1100 HPLC system coupled to a Micromass Ultima MS/MS was umosneidttoorianngal(ySzReMt)h.e sSaammpplleesexwtrearcetse.xAtrnaacltyesdisonwa5s/1p6e/r0f0oarnmdedanuasliynzgesdelbeyctMeSd /reMaSctioonn 5H/P18L/C00a.nSdaMmpSl/eMMSC-me1t0h8oHdswuassedexftorracatneadlyosnis5/a2n2d/i0n0satnrudmaennatlpyazreadmoetne5r/s23c/a0n0.beThfoeund in attachment D. Analysis 5.1 Calibration A 7-point calibration curve was analyzed at the beginning and endofthe analytical sequence 5fo0r0,thaencdo1m0p0o0unngd/sLo(fppitn)teTrehset.rTehspeocnasleiobfratthieonqupaonitnittsawtieorneipornevpearrseuds atthe0,co2n5c,e5n0t,ra1t0i0o,n 2w5a0s,. pcloortrteeldatfioorncacocehffpoiicnite.ntUs(ri)nganldinecaorerfefgirceisesnitonofwidtehte1/rxmiwneaitgihotning(,)theweslroeped,eyt-eirnmteirnceedp.t anAd calibration curve is acceptable ifr >0.985 (7 > 0.970). Calibration standards are prepared using the same SPE procedure used for samples. Cinajleicbtriaotniso)nthcrhoeucgkhousttatnhdeaarndaslywseisreseqauneanlcyez.edCopmeprliioadinccaelliys o(betvaeirnyeditfhrtehee sttoanfdiavred sanaamlpytlee. concentrations are within +/-20%ofthe actual valu. For the results reported here, calibration criteria were met. 52 Blanks eExxttrraaccttiioonnbbllaannkkssswheorueldprneoptahreadveanadnyantaarlgyezteadnwaliyttheesvperreyseenxttraatctoiroanbboavtechthoefcsoanmcpelnetsr.atTihoen of the low-level calibration standard. compliant. For these samples, the extraction blanks were Instrument blanks in the formofclean methanol solvent were also analyzed afier every highlheavveel caanlyibrtaatrigoent satnaanldyatreds, parnedseanftteratknorowanbohviegh-tlheevellows-almepvleels.calAigbariant,iotnhestbalnadnakrsd.shoFuolrd ntohte samples presented here the instrument blanks are compliant. 53 Surrogates Surrogate spikes are not a componentof the LC/MS/MS analytical method. S54 Matrix Spikes M1a0t0rnigx/sLpiukseisngwealrlecpormeppoaruenddsfoorfeinvteerryesfti.eldMsaatmrpixlesp(iekxeclruedcionvgerbileasnkasr) gativaecnoninceAntttraactihomnenotf -- na 000157 C. All laboratory matrix spikes showed recoveriesofall compounds between 70-130% Field spikes were prepared on sample MC-101H at a concentration of 100 ng/L using all compounds of interest. Field spike recoveries are also given in Attachment C. PFOSA showed low recovery in the field spike. All other compounds showed recoveries between 70-130%. 55 Duplicates All field samples (excluding blanks) were analyzed in duplicate. Results are given along with the sample results in Attachment B. 5.6 Laboratory ControlSamples Milliq water was spiked with all compoundofinterest at 25 and 250 ng/L. All recoveries for all compounds were between 70-130% in each LCS. Recoveries are given with the raw data in Attachment D. 5.7 Sample Related Comments Field blank samples consisted ofempty containers. Forty millilitersof type I water filtered through a hypercarb cartridge was added to the empty container and analyzed in the same manner as the other samples. Data Summary Please see Attachment B for a detailed listingof the analytical results Data/Sample Retention Samples are disposedof one month after the report is issued unless otherwise specified. All electronic data is archived on retrievable media and hard copy reports are stored in data folders maintained by Centre. Attachments 11 Attachment A: Chain-of-Custody 12 Attachment B: Results. 83 Attachment C: Matrix Spike Recoveries (Field and Laboratory Spikes) 84 Attachment D: LC/MS/MS Raw Analytical Data Dr Iti some Ror FOS ppenic. ws 000158 9 Signatures -- John M. Flaherty, Operati_ ons Manager -- Date e Kevin JLioyd, Vice President Date Other Lab Members Contributing to Data EKanraeknshSamiWtihckromesinhe David Boll Dv nil sent Report POS Append ne 000159 Analytical Results W1973 Cleveland, Tennesse Id3eMntSifaimcpaltieon MC-101H MC-103H MC-106H NA NAMC-107H MC-108H DeSsacmrpilpetion Site 1 PIN Surface Water Site 1 P/N Surface Water Duplicate Site 2 P/N Surface Water Site 2 P/N Surface Water Duplicate SSiittee 33 PPI/NN SSuurrffaaccee WWaatteerr Duplicate Field Blank P/N Empty PFOS (ng/L) (PnFglOLS)A 14.7 .J 564 < 25 <25 < 25 <25 < 25 <25 << 2255 <<2255 <25 <25 POAA (nglL) 16.74 <25 <25 <25 <<2255 <25 eJs--tiCmoatmepdovuanldue.is present, but below the reporting limit of 25 ng/L. The result is an Method Detection Limits are approximately 2.5 nglL for PFOS and PFOSA and 7.5 ng/L for POAA, OviAsner spor PROS pnts wr 0001.50 Analytical Report Fluorochemical Characterization of Surface Water Samples Decatur, Alabama (W1979) Centre Analytical Laboratory Report No. 023-0148 ------------eee ee i Testing Laboratory Centre Analytical Laboratory, Inc. 3048 Research Drive State College, PA 16801 3M Environmental Laboratory Contact Kent R. Lindstrom Bldg. 2-3E-09 P.O. Box 33331 St. Paul, MN 55133-3331 Phone: (651) 778-5352 Requester Kris J. Hansen, Ph.D. 3M Environmental Technology & Safety Services Bldg. 2-3E-09 P.O. Box 33331 St. Paul, MN 55133-3331 ous.Introduction Results are reported for the analysis oaf seriesof surface water samples received by Centre Analytical Laboratories, Inc. (Centre) from the 3M Environmental Laboratory. The samples were collected from Decatur, Alabama. The Centre study number assigned to the project is 023- Specific fluorochemical characterization by liquid chromatography / tandem mass spectrometry (LC/MS/MS) was requested for all samples. A totalof 9 samples were received for analysis. Ort itcseersPFS.Appnd1c i0s 00161 `The samples were fluorochemicals: prepared and analyzed by LC/MS/MS for the following list of Table I: Target Analysis [ CompoundN|ame `oTnhefialneawliyttihcaClenmteret.hoDdautsaepdrewsaesntveadlihdearteedisbtyheCehnitgrhee.stTqhuealviatlyiddaattaioanvpairloatbolceolatatnhdisretsiumlet.s are Sample Receipt Tinhdeivsiadmupallessamwpelree csounbtmaiitnteerds iwnerinedirveicdeuiavledp.laSstaimcpcloentMaCin-e2rs02anHdwwaesrenontotanparleysezrevdeda.s pNerincelient r0e5q/u0e3s/t0.0.(E-Tmhaeilsacmopmlmeunciolclaetcitoionn fdraotmesKwreirseHanontsesnupoplnie5d/1.6/C0h0)a.inS-oafm-pcluesstowdeyreinrfeocremiavteidononis presented in Attachment A. Holding Times `The analytical stabilityof the method used was validated against a maximum holding timeof analytesofinterest for longer periods has not been determined. 14 days. The Methods - Analytical and Preparatory 41 LOMSMS 4.11 Sample Preparation for LC/MS/MS Analysis Sraemmpolveesrweseirdeuailnicthilaolrliynter.eaStoeldidwipthhas2e00exutLracotfi2o5n0(SmPgE/)Lwsaosdiusuemdtthoiopsruelpfaatree stohleustiaomnpltoes cfaorrtrLiCdg/e.MST/hMeScaanratlryisdigse. waAsffoirrtsty-emliultlelditweirtphor5timoLnooffs4a0m%plmeewtahasntorlanisnfewrarteedrtsoolautCi,o,n.SPE "mTlhepoerltuiaotne wofasmedtihsacnaorldewdaasndcotlhleecStPedEfcoorlaunamlnyswiassbtyheLnC/elMuSt/edMSwi.thTh1i0s0t%remaettmheanntolr.esuAlte5d in an cight-fold concentrationof the samples priotro analysis. 41.3 Sample Analysis by LC/MS/MS cTnhrHoPmLatCo,graanpahliicqucootluomfenx.traBcatsesdionnjetchteedafafninditpyaosfstehdetharnoaulgytheafloirqtuhied-spthaatsieonary phase in athmeoucnotluomfntirmeel.atiFveoltlootwhiengliHquPidLmCobsieplaerapthiaosne,, EtShe/aMnSalpyrtoeviisderestaairnaepdidfaonardcahcacruarctaetreistic mEleeacntsrofsoprraaynailsygzeinnegraalwlyidoeperraantgeed oaftorreglaantiivcelcyommiploduntedmsp,eriantculruedsi;ngmoflleuocruolcehsemairceailosn.ized, fragmented, and detected. Ions quantitated against standards. characteristicofknown fluorochemicals are observed and ra ntlAssis Ror FOS Append wo 000152 AuseHdewtloeatnta-lPyazcekatrhed sHaPm1p1l0e0exHtrPaLctCs.sAynsatleymsicsouwpalsedpetrofaorMmiecdroumsiansgssUellteictmeadMreSa/ctMiSonwas m5/o1n9i/t0o0rianngd(5S/R2M0/)0.0.SaTmhpeleHsPwLeCreaenxdtrMaSct/eMd Sonm5e/t1h6o/d0s0uasneddafnoarlaynzaeldysbiys ManSd/MinSstbreutmewneten `parameters can be found in attachment D. Analysis SI Calibration Afor7-tphoeicntomcaploiubrnadtsioonfciuntrevreeswta.sTahnealcyazleidbraattitohne bpoeignitnsniwnegreanpdreepnadorfedthate0a,na2l5y,ti5c0a,l 1s0e0q,ue25n0c,e p5l0o0t,teadndfo1r 0e0a0chnpgo/iLnt(.pptU)siTnhgelrienesaprornesgeroefsstihoenqwuiatnhti1t/axtiwoenigihotnivnegr,stuhse tshleopceo,ncye-innttreartcieopnt waansd ccaolrirberlaattiioonn ccuorevfefiicsieanctcep(1t)abalnedifco>eff0i.c9i8e5nt( of > determination 0.970). () were determined. A Calibration standards are prepared using the same SPE procedure used for samples. Cinajleicbtriaotniso)nthcrhoeucgkhousttatnhdeaarndaslywseisreseqauneanlcyez.edCopmeprliioadniccaelliys o(betvaeirnyeditfhtrheee sttoanfdiavred sanaamlpyltee concentrations are within +/-20%ofthe actual value. For the results reported here, calibration criteria were met. 52 Blanks eExxttrraaccttiioonnbbllaannkkssswheorueldprneoptahreadveanadnyantaarlgyezteadnwaliyttheesvperreyseenxttraatctoiroanbboavtechtohfe csoanmcpelnetsr.atTihoen of the low-level calibration standard. compliant. For these samples, the extraction blanks were Ilenvsetlrucamleinbtrabtliaonnksstainndtahred,foarnmdoaffctlereaknnomwenthhaingohl-lseovlevlenstamwpelrese.alAsogaainna,lytzheedblaafnlksesvheoruylhdingoht- have any target analytes present at or samples presented here the instrument above blanks the are low-level compliant calibration standard. For the 53 Surrogates Surrogate spikes arc not a component of the LC/MS/MS analytical method. 5.5 Matrix Spikes 1M0at0rnigx/Lspiukseisngwealrlecpormeppoaurenddsfoorfevinetreyrefsite.ldMsaatmrpixlesp(iekxecrleucdoivnegribelsanakrse) gativaecnoinnceAntttraactihomnenotf C. All laboratory matrix spikes showed recoveriesofall compounds between 70-130% cFioemlpdosupnidkessowferineteprersetp.areFdieolnd ssapmikpelereMcCov-e2r0ie1sHarate aalcsooncgeinvternatiinonAtotfa1c0h0menngt/LC.usiPnFgOalSl showed high 70-130%. recovery in the field spike. All other compounds showed recoveries between Dra nilsscsmReerposrtPOS-Append "5001.63 57 Duplicates All field samples (excluding blanks) were analyzed in duplicate. with the sample results in Attachment B. Results are given along 5.8 Laboratory Control Samples Mfoirllaillqcwoamteprouwnadssspwiekreedbweittwheaelnl c7o0m-p1o3u0n%dinofeaicntherLeCsSt.at 2Re5caonvedr2i5es0 anrge/Lg.ivAelnlwrietchovtehreies raw data in Attachment D. 5.7 Sample Related Comments Field blank samples consistedof empty containers. filtered through a hypercarb cartridge was added to Forty milliliters of type the empty container and I water analyzed in the same manner as the other samples. Data Summary Please sec AttachmentB fora detailed listing of the analytical results Data/Sample Retention `Samples are disposedofone month afte the report is issued unless otherwise specified. All electronic data is archived on retrievable media and hard copy reports are stored in data folders maintained by Centre, Attachments 13 Attachment A: Chain-of-Custody 14 Attachment B: Results. 83 Attachment C: Matrix Spike Recoveries (Field and Laboratory Spikes) 84 Attachment D: LC/MS/MS Raw Analytical Data rat niin sss Report PROS Append 1 "$00164 9 Signatures John M. Fiaherty, ManagerOperations Manager Date TE KevinJ Lloyd, Vice President Date `Other Lab Members Contributing to Data KEanraeknshSamiWtihckremesinhe David Bell Dv nit AssessmentReportPFOS- Append If maz 000165 Analytical Results W1979 Decatur, Alabama 3M Sample Identification Sample Description PFOS (ng/L) PFOSA (nglL) POAA (nglL) MC-201H MC-203H MC-206H NA MC-207H NA MC-208H MC-284H NA Site 1 P/N Surface Water 23.1J <25 924 Site 1 P/N Surface Water ~~ 8.3 <25 <25 Duplicate Site 2 PIN Surface Water 14.5 J <25 <25 Site 2 P/N Surface Water 22.0 J <25 1.19 Duplicate Site 3 P/N Surface Water ~~ <25 Site 3 P/N Surface Water ~~ <25 <25 <25 <25 <25 Duplicate Field Blank P/N Empty <25 <25 <25 Quiet PIN Surface 108 18.94 63.1 Water Quiet P/N Surface Water ~~ 114 Duplicate 18.14 57.3 J = Compound is present, but below the reporting limit of 25 ng/L. The result is an estimated value, Method ng/L for Detection POAA. Limits are approximately 2.5 ng/L for PFOS and PFOSA and 7.5 Dr na cstRepo PFOS Appi 1 as 000166 Analytical Report Fluorochemical Characterizationof Surface WaterSamples Pensacola, FI (W2176) Centre Analytical Laboratory Report No. 023-014C e--e--------remeere------eme Testing Laboratory oe Centre Analytical Laboratory, Inc. 3048 Research Drive State College, PA 16801 ST iis 3M Environmental Laboratory Contact Kent R. Lindstrom Bldg. 2-3E-09 P.O. Box 33331 St. Paul, MN 55133-3331 Phone: (651) 778-5352 e-- e ---------------- Requester Kris J. Hansen, Ph.D. 3M Environmental Technology & Safety Services Bldg. 2-3E-09 P.O. Box 33331 St. Paul, MN 55133-3333 Introduction Results are reported for the analysis ofa seriesofsurface water samples received by Centre Analytical Laboratories, Inc. (Centre) from the 3M Environmental Laboratory. The samples. were collected from Pensacola, FI. The Centre study number assigned to the project is 023-014. Specific fluorochemical characterization by liquid chromatography/ tandem mass spectrometry (LC/MS/MS) was requested for all samples. A total of 8 samples were received foranalysis. Dr iiAssen epor PEOS Append wae 000167 `The samples were fluorochemicals: prepared and analyzed by LC/MS/MS for the following lst of Table 1: Target Analysis [CC CompoundName [1] [ Perfluor Sulo fonao te| ct _a_ n| e CC Perfluorcocta| n_c__ate o`TnhefialneawliyttihcCalenmteret.hoDdautsaepdrewsaesntveadlihdearteedisbtyheCehnitgrhee.stTqhuealviatlyiddaattiaoanvpairloatbolceolatatnhdisretsiumlet.s are Sample Receipt `iTnhdeivsiadmupallessawmpelree csounbtmaiitnteerds iwnerinedirveicdeuiavledp.laSstaimcpcloenstawienreresraencediwveedreonno0t5/p0r3e/s0e0r.vedT.heSisxatmepelne collection dates were not supplied. Chain-of-custody information is presented in Attachment A. Holding Times `The analytical stabilityofthe maneatlhyotdesuosfeidntwearessvtafloirdaltoendgeargapienrsitoadsmhaaxsinmout mbeheonlddientgertmiimneeod.f 14 days. The Methods - Analytical and Preparatory 41 LOMS/MS 4.11 Sample Preparation for LC/MS/MS Analysis rSaemmpolveesrweseirdeuailnicthilaolrliynter.eaStoeldidwipthhas2e00exutrLacotfi2o5n0(SmPgE/)Lwsaosduisuemdtthoiopsruelpfaatree stohleustiaomnpltoes cfaorrtLriCd/geM.ST/hMeScaanratlryisdigse.waAsffoirrtsty-lmuiltleidltweirtphor5tmioLnooffs4a0m%plmeewtahasntorlanisnfewrarteedrtsoolautCi,o,n.SPE `mTlhepoerltuiaotneowfasmedtihsacnaorldewdaasndcotlhleecStPedEfcorolanuamlnyswiassbtyhLenC/elMuSt/eMd Sw.ithTh1i0s0t%remaettmheanntolre.suAlted in an cight-fold concentrationofthe samples prior to analysis. 4.1.4 Sample Analysis by LC/MS/MS In HPLC, an aliquotofextract is injected and passed through a liquid-phase cthherocmoaltuomgnrarpehliatcivceoltoumtnh.e lBiqausieddmoonbitlhee pahffaisnei,tytohfe atnhaelayntaeliystereftoarintehde fsotrataiocnhaarraycptheraissetiicn `ammeoaunnstfoofr atniamle.yziFnogllaowwiidneg rHaPngLeCofsoepragraantiiocn,coEmSp/oMunSdpsr,oviindcelusdainrgapfilduoarnodchaecmciucraaltse. Eflreacgtmreonstperda,y ainsdgedneetercatleldy. opTeornastecdhaartacrteelraitsitviecloyfmiklndotwenmpfelruaotruorcehse;mmiocallescualreesoabrseerivoenidzeadn,d quantitated against standards. Dra ilAssen:ReportPROS Append was 00018 AuseHdewtloeatnta-lPyazcekatrhed sHaPm1p1l0e0exHtrPaLctCs.sAynsatleymsicsouwpalsedpetrofaorMmiecdroumsiansgssUelltecitmeadMreSa/ctMiSonwas m5/o1n9i/t0o0.riTnghe(SHRPM)L.CSaanmdpMleSs/wMeSremeextthroadcsteudsoend 5f/or17a/n0a0lyasnisd aanndaliynzsetdrubmyenMtSp/aMraSmeotners can be found in attachment D. Analysis 5.1 Calibration Afor7-tphoeicntomcaploiubrnadtsioonficnutrevreeswta.sTahnealcyazleidbraattitohne bpoeignitnsniwnegreanpdreepnadorfedthate0a,n2al5y,ti5c0a,l 1s0e0q,ue2n5c0e,. p5l0o0t,teadndfor10e0a0chnpgo/iLnt(.ppUt)siTnhgelrienesaprornesgeroefsstihoenqwuiatnhti1t/axtiwoenigihotnivnegr,stuhse tshleopceo,ncye-innttreartcieopnt waansd ccaolrirberlaattiioonn ccuorevfefiicsieanctcep(rt)abalnedifcro>ef0fi.c9i8e5nt(o1>f determination 0.970), () were determined. A Calibration standards are prepared using the same SPE procedure used for samples. Cinajleicbtriaotniso)nthcrhoeucgkhousttatnhdeaarndaslywseisreseqauneanlcyez.edCopmeprliioadinccaelliys o(betvaeirnyeditfhrtehee sttoanfdiavred asnaamlpyltee concentrations are within +/-20%ofthe actual value. For the results reported here, calibration criteria were met. 52 Blanks eExxttrraaccttiioonnbbllaannkkssswheorueldprneoptahreadveanadnyantaarlgyezteadnwaliyttheesvperreyseenxttraatcotiroanbboavtechtohfe csoanmcpelnetsr.atTihoen of the low-level calibration standard. compliant. For these samples, the extraction blanks were lIenvsetlrcuamleinbtrabtliaonnkssitanntdhared,foarnmdoaffctlereaknnomwetnhhaingohl-sloevlevlenstawmpelrees.alAsogaainna,lytzheedbalfatneksevsehroyulhdingoht- have any target analytes present at or samples presented here the instrument above blanks the are low-level compliant. calibration standard. For the 53 Surrogates Surrogate spikes are not a component ofthe LC/MS/MS analytical method. 5.6 Matrix Spikes M1a0t0rnigx/sLpiukseisngwealrlecpormeppoaurenddsfoorfevinetreryesfti.eldMsaatmrpixlesp(iekxeclruedcionvgerbileasnkarse) gativaecnoninceAntttraactihomnenotf C. All laboratory matrix spikes showed recoveriesofall compounds between 70-130% Field spikes compounds were prepared on of interest. Field sample MC-301H at spike recoveries are a concentration of 100 ng/L also given in Attachment C. using all All field spikes showed recoveriesofall compounds between 70-130%. Of nia AsrsmenReposPFS-Append 1 us 000159 59 Duplicates All field samples (excluding blanks) were analyzed in duplicate. with the sample results in Attachment B. Results are given along 5.10 Laboratory Control Samples Mfoirllaillq cwoamteprouwnadssspwiekreedbweittwheaelnl c7o0m-p1o3u0n%dionfeaicntherLeCstS.at R2e5caonvedr2i5es0 anrge/Lg.ivAelnl wriectohvtehreies raw data in Attachment D. 5.7 Sample Related Comments Field blank samples consistedofempty containers. filtered through a hypercarb cartridge was added to Forty millilitersof typIe water the empty container and analyzed in the same manner as the other samples. Data Summary Please sce Attachment B for adetailed listingof the analytical results. Data/Sample Retention Samples are disposed of one month afte the report is issued unless otherwise specified. All electronic data is archived on folders maintained by Centre, retrievable media and hard copy reports are stored in data Attachments 15 Attachment A: Chain-of-Custody 16 Attachment B: Results. 83 Attachment C: Matrix Spike Recoveries (Field and Laboratory Spikes) 84 Auachment D; LC/MS/MS Raw Analytical Data Dr IiAssen ReprPOS Appencic war 0001770 9 Signatures JohnM. Faherty, Operations Manager KeJLvoydi,Vince President Other Lab Members Contibuting to Data EKanraeknshSamiWtihckremesinhe David Bell Tate -- Date Dra ilAsset Report POS ppentic as 000171 Analytical Alabama Results W1979 Decatur, Id3eMntSifaimcpaltieon DeSsacmrpilpteion PFOS (ng/L) PFOSA (nglL) POAA (ng/L) MC-201H MC-203H MNCA-206H MNCA-207H MC-208H MC-284H NA Site 1 PIN Surface Water Site 1 PIN Surface Water 23.1.J 8.3J <25 <25 924 <25 DSiutpeli2caPtIeN Surface Water 14.5J <25 <25 Si2tPIeN Surface Water Duplicate 22.0.J <25 1.19 Site Site 3 3 PIN PIN Surface Surface Water Water <25 <25 <25 <25 <25 <25 Duplicate Field Blank PIN <25 <25 <25 QEumipettyPIN Surface 108 18.94 63.1 Water Quiet P/N Surface Water Duplicate 114 18.19 57.3 J - Compound is estimated value. present, but below the reporting limit of 25 ng/L. The result is an Method ng/L for DPeOtAeAct.ion Limits are approximately 2.5 ngiL for PFOS and PFOSA and 7.5 Dra nitAsses Repo POS ppei wa 000172 Analytical Report Fluorochemical Characterization of Surface WaterSamples Mobile, Alabama (W2151) Centre Analytical Laboratory Report No. 023-014D -- eee--r---- Testing Laboratory Centre Analytical Laboratory, Inc. 3048 Research Drive State College, PA 16801 --eeeeee---- 3M Environmental Laboratory Contact Kent R. Lindstrom Bldg. 2-3E-09 P.O. Box 33331 StP.hoPnauel:, (M6N51)55717383--53335321 nnn Requester Kris J. Hansen, Ph.D. 3M Environmental Technology & Safety Services Bldg. 2-3E-09 P.O. Box 33331 St. Paul, MN 55133-3331 Introduction 014Results are reported for the analysis ofa seriesofsurface water samples received by Centre Analytical Laboratories, Inc. (Centre) from the 3M Environmental Laboratory. The samples were collected from Mobile, Alabama. The Centre study number assigned to the project is 023- Specific fluorochemical characterization by liquid chromatography/ tandem mass spectrometry (LC/MS/MS) was requested for all samples. A total of8 samples were received for analysis. DrtasceaesPmOS ppd1 ao 000173 The samples were fluorochemicals: prepared and analyzed by LC/MS/MS for the following lst of Table I: Target Analysis o`TnheflaenawliyttihcaClenmteret.hoDdautsaepdrewsaesntveadlihdearteedisbtyheCehnitgrhee.stTqhuealviatlyiddaattaioanvpairloatbolceolatatnhdisretsiumlet.s are `Sample Receipt i`Tnhdeivsiadmupallessamwpelree csounbtmaiitnteerds iwnerinedrievciediuavledp.laSstaimcpcloenstawienreersraencediwveedreonno0t5/p0re3s/e0r0v.edT.heEisgahmtple collection dates were not supplied. Chain-of-custody information is presented in Attachment A. Holding Times sTthaebilaintaylyotfictahle maneatlhyotdesuosfedinwtearsesvtafloirdaltoendgeargapienrsitoadsmhaaxsinmoutmbeheonlddientgertmiimneedo.f 14 days. The Methods - Analytical and Preparatory 41 LOMSMS 4.11 Sample Preparation for LC/MS/MS Analysis rSeammpolveesrweseirdeuailnicthilaolrliynter.eaStoeldidwipthhas2e00exutLr.aocfti2o5n0(SmPgE/)Lwsaosduisuemdtthoiopsruelpfaatree stohleustiaomnplteos cfaorrtrLiCdg/e.MST/hMeScaanratlryisdigse. waAsffoirrtsty-emliultleldtweirtphorStmioLn ooffs4a0m%plmeewtahasntorlanisnfewrarteedrtsoolautCioon.SPE mTlhepoerltuiaotneowfamsetdihsacnaorldewdaasndcotlhleecStPedEfcorolaunamlnyswiassbythLenC/elMuSt/edMSwi.thTh1i0s0t%remaettmheanntolr.esuAlte5d in an cight-fold concentrationof the samples prior to analysis 4.15 Sample Analysis by LC/MS/MS cInhrHoPmLatCo,graanpahliicqucootluomfne.xtrBaacsteids ionnjetchteedafafninditpyaosfsetdhetharnoaulygtheafloirqtuhied-sptahtaisoenary phase in athmeoucnotloufmntirmeel.atiFveoltlootwhiengliHquPidLmCobsieplaerapthiaosne,,EtShe/aMnSalpyrtoeviisdersetaairnaepdidfoarnacdhaarcaccutraetreistic Emleeacntsrofsoprraaynailsygzeinnegraalwlyidoeperraantgeedoaft orrelgaatniivcelcyommiploduntedmsp,eriantculruedsi;ngmoflleucoruolcehsemaircailosn.ized, fragmented, and detected. lons quantitated against standards. characteristicofknown fluorochemicals arc observed and Dre iilAsssmes Ber POS Append war 000174 AuseHdewtloeatnta-lPyazcekatrhed sHaPm1p1l0e0exHtrPacLtsC. sAynsatleymsicsouwpalsedpetrofaorMmiecdroumsiansgssUellteictmeadMreSa/ctMiSonwas `5m/o20n/i0t0o.rinTgh(eSHRMP)L.CSaanmdplMeSs/wMerSemeextthraocdtsedusoend5f/o1r7a/n0a0laysnids aannadlyiznesdtrbuymeMntS/paMrSamoenters an be found in attachment D. Analysis SI Calibration Afor7-tphoeicntomcaploiubrnadtsioonficnutrevreeswta.sTahnealcyazleidbraattitohne bpoeignitnsniwnegraenpdreepnadrofedthate0a,n2al5y,ti5c0a,l1s0e0q,ue25n0c,e 5pl0o0t,teadndfor10e0a0chnpgo/iLnt(.ppUt)siTnhgelriencsaprornesgeroefstshioenqwuiatnhti1taxtiwoenigihotninvge,rstuhsetshleopceo,nyc-einnttreartcieopnt waansd. correlation calibration coefficient (r) and coefficient of curve is acceptable if > 0.985 ( > determination 0.970). () were determined. A Calibration standards are prepared using the same SPE procedure used for samples. iCnajleicbtriaotniso)nthcrhoeucgkhousttatnhdeaarndaslywsiesreseqauneanlcyez.edCompeprliioadniccaellisyob(teaveirnyedtihftrehee sttoanfdiavred sanaamlpyltee `concentrations are within +/-20%ofthe actual value. For the results reported here, calibration criteria were met 52 Blanks eExxttrraaccttiioonnbbllaannkksswsheoruelpdrneoptarheadveanadnyantaarlgyeztedanwailyttheesvperreyseenxttraatcotiroanbboavtechtohfe csoanmcpelnetsr.atTihoen of the low-level compliant. calibration standard. For these samples, the extraction blanks were Ilenvsetlrcuamleinbtrabtliaonnksstainndtahred,foarnmdofaftcelrekannomwetnhhaingohl-lseovlevlenstamwpelrese.alAsogaainna,lytzheedblafatnekrsesvheoruylhdingoht- have any target analytes present at or samples presented here the instrument above blanks the are low-level compliant, calibration standard. For the 53 Surrogates Surrogate spikes are not a component of the LC/MS/MS analytical method. 5.7 Matrix Spikes M1a0t0rnigx/sLpiukseisngwealrlecpormeppoaruenddsfoorfevinetreryesfti.eldMsaatmrpixlesp(iekxeclruedcionvgerbileasnkasr)e agtivaecnoinnceAntttraactihomnenotf oC.thePr OcoAmAposuhnodwsedshloowwemdatmraitxrisxpiskpeikreescorveecroiveesriienssbaemtpwleeesnM7C0--410307%HiannadllMsCa-m4p8le4sH.. All cFioemlpdosupnidkess owferienteprreespt.aredFioenldsaspmipklee rMeCc-ov4e0ri1eHs aatrea caolnsocengtirvaetnioinnoAft1t0a0chnmge/nLtuCs.ingAallll `compounds showed recoveries between 70-130%. Dr ni sscsmentReposPEOS Append 1 maz 000175 S11 Duplicates All field samples (excluding blanks) were analyzed in duplicate. Results are given along with the sample results in Attachment B. 5.12 Laboratory Control Samples Mfoirllaillqcwoamteprouwnadssspwiekreedbweittwheaelnl c7o0m-p1o3u0n%dinofeaicntherLeCstS.at 2Re5caonvedr2i5es0 anrge/Lg.ivAelnlwrietchovtehreies raw data in Attachment D. 5.7 Sample Related Comments Field blank samples consistedofempty containers. filtered through a hypercarb cartridge was added to Forty millilitersof type the empty container and I water analyzed in the same manner as the other samples. Data Summary Please see Attachment B for a detailed listingofthe analytical results. Data/Sample Retention Samples are disposedof one month afte the report is issued unless otherwise specified. All electronic data is archived on folders maintained by Centre. retrievable media and hard copy reports are stored in data Attachments 17 Attachment A: Chain-of-Custody 18 Attachment B: Results. 83 Attachment C: Matrix Spike Recoveries (Field and Laboratory Spikes) 84 Attachment D: LC/MS/MS Raw Analytical Data Dra IlAsset Repo FOS Appenic wa 000176 9 Signatures John M. Faherty, Manager-Operations Manager Date Kevin J Loyd, Vice President Date Other Lab Members Contributing to Data KEanraeknshSaiWtihckremesinhe David Boll rat tilAssRoarPmOS Append mas 00dL77 Analytical Report Fluorochemical Characterization of Surface Water Samples Columbus, GA (W2336) Centre Analytical Laboratory Report No. 023-014E Testing Laboratory Centre Analytical Laboratory, Inc. 3048 Research Drive State College, PA 16801 3M Environmental Laboratory Contact Kent R. Lindstrom Bldg. 2-3E-09 P.O. Box 33331 St. Paul, MN 55133-3331 Phone: (651) 778-5352 Requester Kris J. Hansen, Ph.D. 3M Environmental Technology & Safety Services Bldg. 2-3E-09 P.O. Box 33331 St. Paul, MN 55133-3331 Introduction Results are reported for the analysisof a seriesof surface water samples received by Centre Analytical Laboratories, Inc. (Centre) from the 3M Environmental Laboratory. The samples. `owre.re collected from Columbus, GA. The Centre study number assigned to the project is 023- Specific fluorochemical characterization by liquid chromatography / tandem mass spectrometry (LC/MS/MS) was requested for all samples. A total of8 samples were received for analysis. Dr titAssepePnOS Append was 000178 `The samples were fluorochemicals: prepared and analyzed by LC/MS/MS for the following list of Table I: Target Analysis CompowndName [1] [PerfluoSr ulfo onatoe c| ta _n| e L[L PerPef rflul orou octao ncSaur tlefoo nylo amic de |t | an ] e| o`TnhefialneawliyttihcCalenmteret.hoDdautsaepdrewsaesntveadlihdearteedisbtyheCehnitgrhee.stTqhuealviatlyiddaattaioanvpairloatbolceolatanthdisretsiumlet.s are Sample Receipt `iTnhdeivsiadmupallessamwpelree csounbtmaiitnteerds iwnerinedirveciediuvaeld.plaSstaimcpcloenstawienreersraencediwveerdeonno0t5/pr0e3s/e0r0v.ed.TheEisgahmtple collection dates were not supplied. Chain-of-custody information is presented in Attachment A. Holding Times s`tTahbeilaintaylyotfictahle maneatlhyotdesuosfedinwtaersesvtafloirdaltoendgeargapienrsitoadsmhaaxsinmout mbeheonlddientgertmiimneedo.f 14 days. The Methods - Analytical and Preparatory 41 LOMSMS 4.1.1 Sample Preparation for LC/MS/MS Analysis r`Seammopvleesrweseirdeuailnicthilaolrliynet.reaStoeldidwipthhas2e00exutLracotfi2o5n0(SmPgE/)Lwsaosdiusuemdtthoiopsruelpfaatree stohleustiaomnpltoes cfaorrtrLiCdg/e.MST/hMeScaanratlryisdigse. wAasffoirrtsty-emliultlelditweirtphor5tmioLnooffs4a0m%plmeewtahasntorlanisnfewrarteedrtsoolautCi,o,n.SPE m`Tlhepoerltuiatoen owfamsedtihsacnaorldewdaasndcotlhleecStPedEfcoorlaunamlnyswiassbtyhLenC/elMuSt/edMSwi.thTh1i0s0t%remaettmheanntolre.suAlted in an cight-fold concentrationofthe samples prior to analysis 4.1.6 Sample Analysis by LC/MS/MS cTnhrHoPmLatCo,graanpahliicqucootloufmenx.traBcatseids oinnjetchteedafafninditpyaosfstedhetharnoaulgytheafloirqtuhied-spthaatsieo.nary phase in athmeocuonltuomfntriemlea.tiFveoltlootwhiengliHquPidLmCobsieplaerapthiaosne,, EtShe/aMnSalpyrtoeviisdreestaairnaepdidfoarnad cahcacruarctaetreistic `Emleeactnrsofsoprraaynailsygzeinnegraallwyidoeperraantgeedoaft orrelgaatniivcelcyommiploduntedmsp,eriantculruedsi;ngmoflleuocruolcehsemairceailosn.ized, fragmented, and detected. Tons quantitated against standards. characteristic of known fluorochemicals are observed and Dr ni sscsmens Repos PEOS Append 1 nas 000173 AuseHdewtloeatnta-lPyazcekatrhed sHaPm1p1l0e0exHtrPacLtsC. sAynsatleymsicsouwpalsedpetrofaorMmiecdroumsiansgssUellteictmeadMreSa/ctMiSonwas m5/o2n0i/t0o0rianngd(5S/R2M1)/.00.SaTmhpeleHsPwLeCreanedxtMraSc/teMdSonme5t/h1o8d/0s0uasnedd afnoralaynzaeldysbisyaMnSd/iMnsStrbuemtewneten parameters can be found in attachment D, Analysis SI Calibration Afor7-tphoeicntomcaploiubrnadtsionofcuinrtveerewsta.sTahnealcyazleidbraattitohne bpeoginitnsniwnegreanpdreepnadorfedthate0a,na2l5y,ti5c0a,l 1s0e0q,ue25n0c,e 500, and 1000 ng/L (ppt) The response of the quantitation ion versus the concentration was pcloortrteeldaftoiorneaccohefpfoiicnite.ntUs(ri)ngalnidneacroreefgfirceisesnitonofwitdeht1e/rxmiwneaitgihotning(,)thewesrloepe,deyt-eirnmteirnceedp.t anAd calibration curve is acceptable if>r 0.985 ( > 0.970). Calibration standards are prepared using the same SPE procedure used for samples. Cinajleicbtriaotniso)nthcrhoeucgkhousttatnhdeaarndaslywsiesreseqauneanlcyez.edCompeprliioadniccaelliys (every obtained three ifthe to five standard sample analyte concentrations are within +/-20%ofthe actual value. For the results reported here, calibration criteria were met. 52 Blanks eExxttrraaccttiioonnbbllaannkkssswheorueldprneoptahraedveanandyatnaarlgyezteadnwaliyttheesvperreyseenxttraatcotiroanbboavtechthoefcsoanmcpelnetsr.atTihoen of the low-level calibration standard. compliant. For these samples, the extraction blanks were Ilenvsetlrucamleinbtrabtliaonnksstainndtahred,foarnmdoaffctlereaknnomwetnhhaingohl-lseovlevlenstamwpelrees.alAsogaainna,lytzheedblafalnekrsesvheoruylhdingoht- have any target analytes present at or samples presented here the instrument above blanks the are low-level compliant. calibration standard. For the 53 Surrogates Surrogate spikes are not a component ofthe LC/MS/MS analytical method. 58 Matrix Spikes M10a0tinxg/sLpiukseisngwealrlecpormeppoaruenddfsoorfeivneterryesfti.eldMsaatmipxlesp(iekxeclruedcionvgerbileasnkasr)e agtivaecnoinnceAntttraactihomnenotf C.. All compounds showed matrix spike recoveries between 70-130% in all samples. `Fcieolmdposupnikdessowfeirneteprersetp.arFeidelodnsspaimkpelreecMoCve-rSieOs1HareatalascoognicvenetnriantiAotntoafch1m0e0ntngC/.LTuhseinfgiealldl spike results showed low recovery recoveries between 70-130%. for PFOSA. All other compounds showed matrix spike rat nial sso Repos PROS Append 1 war 000180 513 Duplicates All samples (excluding blanks) were analyzed in duplicate. sample results in Attachment B. Results are given along with the 5.14 Laboratory Control Samples fMoirllaillqcwoamteprouwnadssspwiekreedbweittwheaelnl c7o0m-p1o3u0n%dionfienatcehrLesCtS.at R2e5sualnfds2a5r0e gnig/vLe.n aAllolngrewciotvhertihees raw data in Attachment D. 5.7 Sample Related Comments Field blank samples consistedofempty containers. Forty millilitersof type I water filtered through a the same manner hypercarb cartridge as the other samples was added to the empty container and analyzed in Data Summary Please see Attachment B fora detailed listingof the analytical results Data/Sample Retention `Sampleeslaercetrdoinsipcodsaetdaofios narechmiovendthonafrteetrritehvearbelpeomrtediisaisasnudehdaurndlecsospyothreerpworitsseasrpeecsitfoireedd. iAnldlata folders maintained by Centre, Attachments 19 Attachment A: Chain-of-Custody 1.10 Attachment B: Results. 83 Attachment C: Matrix Spike Recoveries (Field and Laboratory Spikes) 84 Attachment D: LC/MS/MS Raw Analytical Data Dra nial sss Report PROS Append 1 was 000181 9 Signatures `John M. Flaherty, Manager-Operations Manager Date _-- KevinJ Lloyd, Vice President Date Other Lab Members Contributing to Data Enaksha Wickremesinhe Karon Smith David Bell ref iit AssessRmeeponrt PF-ApOpenSd 1 mas 000182 Analytical Results W2336 Columbus, GA 3M Sample Identification Sample Description PFOS (ng/L) PFOSA (ngiL) POAA (nglL) MMCC--550013HH MNCA-506H NMCA-507H MC-508H MC-584H NA Site Site 1 1 PIN PIN Surface Surface Water Water 63.8 59.9 Duplicate Site Site 2 2 PIN PIN Surface Surface Water Water ~~ 76.6 83.3 Duplicate Site Site 3 3 PIN PIN Surface Surface Water Water 55.4 55.4 Duplicate Field Blank-PIN <25 QEumipettySurface Water <25 QDuuipleitcSatuerface Water <25 174 264 1324 256 1654 1764 26.4 267 1204 14.94 2364 243) <25 <25 <25 <25 <25 <25 J~ Compound is estimated value. present, but below the reporting limit of 25 ng/L. The result is an Method nglL for DPeOtAeAct.ion Limits are approximately 2.5 ng/L for PFOS and PFOSA and 7.5 [ -- nso 000183 Analytical Report Fluorochemical Characterization of Water and Sediment Samples Port St. Lucie Resampling (E00-2003) Centre Analytical Laboratory Report No. 023-014P ~------------------e-- e. Testing Laboratory Centre Analytical Laboratory, Inc. 3048 Research Drive State College, PA 16801 eee emer 3M Environmental Laboratory Contact Kent R. Lindstrom Bldg. 2-3E-09 P.O. Box 33331 St. Paul, MN 55133-3331 Phone: (651) 778-5352 eem------------------e--. Requester Dale Bacon Ph.D. 3M Environmental Technology & Safety Services PB.0l.dg.Bo2x-33E3-30391 St. Paul, MN 55133-3331 Introduction Results are reported for the analysisof a seriesofwater and sediment samples received by Centre Analytical Laboratories, Inc. (Centre) from the 3M Environmental Laboratory. The samples were collected from Port St. Lucie, Florida and are partof 3M `study number assigned to the project is 023-014. Project E00-2003. The Centre Specific fluorochemical characterization by liquid chromatography/ tandem mass spectrometry (LC/MS/MS) and ion received for analysis. chromatography was requested for all samples. A total of45 samples were Dr issepon rPEOS pent1 an 000184 The samples were fluorochemicals: prepared and analyzed by LC/MS/MS for the following list of Table 1: Target Analysis `The analytical methods protocol and results are uosnefdifloe rwwitahteCrenstarme.pleTshewemreethvoaldisdawteerdebmyoCdeinftireed, The validation for the sediment psraemspelnetse,dhhoewreeviesrthtehehipgrhoecsetduqruaelsihtyavdeatnaotavbaeielanblfeulaltytvhailsitdiamtee.d for this matrix. Data Sample Receipt iTnhdeivsiadmupallessamwpelree csounbtmaiitnteerds iwnerinedirveciediuvaeld.plaSstaimcpcloenstawienreersraencediwveedreonno7t/2p5r/e0s0e.rveTdh.eFsoarmtpyl-efsive were collected Attachment A. between 7/18/00 and 7/19/00. Chain-of-custody information is presented in Holding Times a`fTtheeratnhailsyttiicmael pmeertihododhaussendotwbaesevnavlaildiadtaetdeda,gahionswtevaemraixt ishmouumldhboeldniontgedtitmheatoffie1l4ddfaoyrst.ifSitcaatbiiolnisty have shown acceptable recoveries at the 100 ng/L for periods longer than 14 days. Methods - Analytical 41 LOMSMS and Preparatory 4.11 Sample Preparation for LC/MS/MS Analysis tWoatreermosvaemprleessiduwaelrechilnoirtiinael.lyStorleiadtepdhwaistehe2xt0r0acutLioonf(2S5P0E)mgwa/sL susoeddiutmo ptrheipoasurlefattheesolution CsyasmpSlPeEs cfaorrtrLiCdg/e.MST/hMeScaanratlryisdigse.wAasfofirrtsyt-meillultielditweirtphorStimoLnooff4s0am%plmeewtahasntorlanisnfewrarteedrto a mseoltuhtainoonl..TAhe$emluLatepowratsiodniosfcamredtehdaannodl wthaesScPolEleccotleudmfnorwaansaltyhseins cblyutLeCd/wMiSth/M1S0.0%This treatment resulted in an eight-fold concentrationof the samples prior to analysis fFiorsrttehxetrsaecdtiemdeninttoan5dmslluodfgmeetshaamnpolle.s, Tahreeperxetsreancttastiwveerepofritlitoenroedfasnadmpdilleut(e5dgtroaamsf)inawlas `vmoalnunmeeroafs t4h0emwaLtewritshamTpylpees,Ibweagtienr.ninTghewidtihluttheedseoxltirdacpthsawseereexttrhaecntitorne.ated in the same. 4.1.7 Sample Analysis by LC/MS/MS cInhrHoPmLatCo,graanpahliicqucootloufmenx.trBaactsesd ionnjetchteedafafninditpyoasfstehdetharnoaulygtheafloriqtuhied-spthaatisoenary phase in Dra IlAsset Ror POS ppenic wa 000155 tahmeoucnotloumfntirmeel.atiFveoltlootwhiengliHquPidLmCobseiplaerapthiaosne,, EtShe/aMnSalpyrtoeviisdersetaairnaepdidfoarnadcahcacruacrtaetreistic mEleeacntsrofsoprraaynailsygzeinnegraalwlyidoeperraantgeedofatorreglaantiivcelcyommiploduntedmsp,eriantculruedsi;ngmoflleuocruolcehsemairceailosn.ized, fragmented, and detected. lons quantitated against standards. characteristic of known fluorochemicalsare observed and AuseHdewtloeatnta-lPyazcekatrhde sHaPm1p1l0e0exHtrPaLctCs.sAynsatleymsicsouwpalsedpetrofaorMmiecdroumsiansgssUelltecitmeadMreSa/ctMiSonwas `amnoanliytzoerdinbgy(MSRSM/)M.SWabettewreseanmp8/l1e8s/w0e0raendex8t/r2a3c/t0e0d.bSeetdwiemeenn8t/a15n/d0s0laundgde8s/a1m7/p0l0esanwdere emxettrhaoctdesduosned8/f1o8r/a0n0alaynsdiswaenrde ainnsatlryuzmeednbtypaMrSam/eMteSrsonca8n/2b1e/0f0.ouTndheinHAPtLtaCchamnednMtsSD/MaSnd E Analysis 5.1 Calibration Afor7-tphoeicntomcaploiubrnadtsioonficnutrevreeswta.sTahnealcyazleidbraatttihoen pboeignitnsniwnegraenpdreepnadorfedthate0a,n2al5y,ti5c0a,l1s0e0q,ue2n5c0e, 500, and 1000 ng/L (ppt) `concentration was plotted ffoorrcLacCh/pMoSin/tM. SUsanianlgysliisn.caTrhreegirnesstsriuonmewnitthre1s/pxonwseeigvhetrisnugs, the the. slope, y-intercept and correlation cocfiicient (r) determined. A calibration curve is acceptableif and r> coefficientofdetermination 0.985 (* > 0.970). (r) were Calibration standards are prepared using the same SPE procedure used for samples. Cinajleicbtriaotniso)nthcrhoeucgkhousttatnhdeaarndaslywseisreseqauneanlcyez.edCompeprliioadniccaellisyob(teaveirnyeditfhtrheee sttoanfdiavred sanaamlpyltee concentrations are within +/-20%ofthe actual value. For the results reported here, calibration criteria were met. 52 Blanks eExxttrraaccttiioonnbbllaannkkssswheorueldprneoptahraedveanandyatnaarlgyezteadnwaliyttheesvperreyseenxttraatcotrioanbboavtechtohfe csoanmcpelnetsr.atTihoen of the low-level calibration standard. compliant. For these samples, the extraction blanks were lIenvsetlrcuamleinbtrabtliaonnksstainndtahred,foarnmdofafctlereaknnomwetnhhaingohl-lseovlevlenstamwpelerse.alAsogaainna,lytzheedblaaflnekrsesvheoruylhdingoht- have any target analytes present at or samples presented here the instrument above blanks the are low-level compliant. calibration standard. For the 53 Surrogates Surrogate spikes are not a componentof the LC/MS/MS analytical methods. vat nia sscxsmen Repos PR-ApOpendS1 was 000156 5.9 Matrix Spikes sMpaitkreixrescpoivkeersiewseraerepgrievpearneidnfAotrteavcehrmyefnitelCd.sample using all compoundsof interest. Matrix iFnieAltdtsapcihkmeesnwterC.e sTuhbmeitretseudltwsitfhrotmhetwhaet2er00sapmpptlefsi.eldFiseplidkespfiokresraemcpovleeriQesSaWrePaalslomiCnictlyu-dCe-d FreMsSul-t2s0f0oprpQtSAWiPndailcmatCeitthyat-Ct-hiFsMsSa-m2p0l0eppwtasB sipnidkiecadteata1200000ppppttsrpaitkhienrgtchoannce2n0t0raptpito.n.The 5.15 Duplicates All field samples in Attachment B. were analyzed in duplicate. Results are given along with the sample results 5.16 Laboratory ControlSamples aFnodr 2L5C0/nMgS//LMdSurainnaglyesaecsh, eMxitlrlaicqtiwoantesert.waAsllspriekceodvewriitehs aflolrcaollmcpoomupnodusnofdisntweerreestbeattw2e5en 70-130% in each LCS. E. Results are given along with the raw data in Attachments D and 5.7 Sample Related Comments There are no other sample related comments for this data set. Data Summary rPelseualstes sareee rAetptoarcthemdeinntpaBrtfsorpeardtertialillieond (lpipstti)n(gongf/Lt)h.e Saenadliymteincatlarnesdulstls.udSguersfaamcpelweatreesrults are reported in parts per billion (ppb) (ng/g) on both an as-received and dry-weight basis. Data/Sample Retention Selaemcptlroensicardeatdaisi poasrecdhoifvoednoenmroentrtihevaafbtleer mtheedireapaorntdihsairsdsuceodpyunrleepsosrtosthaerrewsitsoeresdpeicnifdiaedt.a All folders maintained by Centre. Attachments 111 Attachment A: Chain-of-Custody 112 Attachment B: Results. 83 Attachment C: Matrix Spike Recoveries 84 Attachment D: LC/MS/MS Raw Analytical Data (Surface Water Samples) 8.5 Attachment E: LC/MS/MS Raw Analytical Data (Sediment and Sludge Samples) Dr iilAsssmens Report POS ppetic as 000187 9 Signatures _Jo--hn M. Flaherty, Manager- Operations Manager -_ Kevin J Loyd, Vice President Other Lab Members Contributing to Data Karen Smith 3 00 Date ref ilAssn Repor POS pend as 000188 Analytical (solids) Results E00-2003 Port St. Lucie, FL Resampling 3M Sample Identification NPWWTP Sludge-C NPWWTP Sludge-C dup SED #3 SH-C SED #3 SH-C dup SED#1 Penparkc SED#1 Penpark-C dup SED#2 MCM-C SED#2 MCM-C dup PFOS (ug/Kg) (as received) 1.36 1.30 <0.200 <0.200 <0.200 <0.200 <0.200 <0.200 ~ PFOSA (ug/Kg) (as received) <0.200 <0.200 <0.200 <0.200 <0.200 <0.200 <0.200 <0.200 POAA (ug/Kg) (as received) <0.200 <0.200 <0.200 <0.200 <0.200 <0.200 <0.200 <0.200 3M Sample Identification NPWWTP Sludge-C NPWWTP Sludge-C dup SED #3 SH-C SED #3 SH-C dup SED#1 Penparkc SED#1 Penpark-C dup SED#2 MCM-C SED#2 MCM-C dup PFOS (ug/Kg) (dry weight) 629 602 <0.261 <0.261 <0263 <0263 <0.304 <0.304 PFOSA (ug/Kg) (dry weight) <93 <93 <0.261 <0.261 <0.263 <0263 <0304 <0.304 POAA (ug/Kg) (dry weight) <93 <93 <0.261 <0.261 <0263 <0.263 <0304 <0304 J - Compound value. is present, but below the reporting limit. The result is an estimated raf nis ssxsmen Repos PROS Append 1 mae ens APPENDIX IV PLANNED ENVIRONMENTAL STUDIES ON PERFLUOROOCTANE SULFONATES (PFOS) [eT ---- wo con150 `PTLheA3NMNECoDmpEaNnVyIiRs pOlNanMnEinNgTtoAcLonSdTucUtDsIevEeSraOl NstuPdiEesRiFnLthUrOeeRsOubOjeCctTaAreNasE: S(1U)LeFnvOiNroAnmTeEntSal sfaatmepalnidngtraanndsproretl,ea(s2e)ecsctiomtaotxiionc)t.y sTtuhdeisees,satunddie(s3)areenvliirstoendmienntTaalblmeonIiVt-1o.ring (environmental `Table IV-1. Planned Environmental Studies on Perfluorooctane Sulfonates (PFOS) Environmental Fate and Transport Soil and sediment adsorption/desorption | 3M Environmental Laboratory Multi-media modeling of PFOS distribution D. Mackay, Trent University Underway Underway Bioconcentration in bluegill sunfish `Wildlife International, Ltd. Biodegradability closed bottle - acrobic, acclimated | Springbom Laboratories, Inc. |Underway Biodegradability - aerobic soi/sediment | Springborn Laboratorics, Inc. spBeicoideegsr)adability - aerobic, pure culture (4| ISnpcr.ingbor Laboratories, | Underway Biodegradability - anaerobic Hydrolysis Hydrolysis on soils Photolysis Photolysis with humic matter Photolysis with metals. Photolysis with soils `Springbom Laboratories, Inc. 3M Environmental Laboratory 3M Environmental Laboratory 3M Environmental Laboratory 3M Environmental Laboratory 3M Environmental Laboratory 3M Environmental Laboratory Underway Underway Underway Underway Underway Underway Solubility - Confirmation Tests 3M Environmental Laboratory Underway Activated sludge sorption isotherm Brat ial vse Report PFS pend 17 3M Environmental Laboratory Underway wT 0on191 `Table IV-1. Planned Environmental Studies on Perfluorooctane Sulfonates (PFOS) Photolysis - atmospheric Ecotoxicity Studies 3LaMboErnavtiorryonmental Underway 9in6h-iHbritAinonabaenaflos-aquae growth `Wildlife International, Ltd. |Underway 96-Hr Navicula inhibition pelliculosa growth `Wildlife International, Ltd. |Underway 96-Hr Skeletonema inhibition costatum growth `Wildlife International, Ltd. [Underway 7-day Lemna gibba growth inhibition `Wildlife International, Ltd. Puphtyatkoetox - seedling emergence and plant | Wildlife International, Ltd. |Underway FETAX (frog embryo teratogenesis) `LWtidldlUifneivIenrtseirntaytioofnal, Maryland Underway Histo-pathological mallard duck pilot reexparomodufcttiiosnsues from | EPI Laboratory Underway bHoisbtwoh-iptaethqoulaoiglicpaillotexreapmroofdtuicstsiuoens from |EPI Laboratory Pilot final study on mallard duck comprehensive report reproduction -|Wildlife Intemational, Ltd. Underway [Underway Pilot study on reproduction - bobwhite quail final comprehensive report `Wildlife International, Ltd. [Underway Emavlallauradtiaonnod fquPaiFlOpSilpotrostteuidnybsipnedicnigmeunssing| Michigan State University |Underway tViaslsiudeastoifonmaalnldadredtaenrdmiqnuaatiilon of PFOS in |Centre Analytical `Acute toxicity (0 bluegill sunfish `Wildlife International, Inc. Acute toxicity to sheepshead minnow | Wildlife Intemational, Inc Underway Acute toxicity to honeybees - oral & contact exposure: Acute toxicity \foetida) to earthworm (Eisenia Mallard duck reproduction (dietary) Ey --r-------- |Wildlife Intemational, Inc.|Underway `Wildlife International, Inc. | Underway `Wildlife Intemational, Inc. wa C00192 foTable IV-1. Planned Environmental Toman Studies on Perfluorooctane Jon Sulfonates (PFOS) effluent sample points Multi-city sample results biosphere sampling. 000193 APPENDIX V ROBUST SUMMARIES Dr itlAssessment Repors Append V va 000194 ROBUST | TITLE SUMMARY # st RS2 RS3 RS4 RST RS8 RRSS1Y0 Rs11 RS1Z RST3 RSTS RS16 | Eye Irritation Report on Sample T-1117, 1974 An Acute Inhalation Toxicity StudyofT-2306 CoC in the Rat. 1979 | Fluorad Fluorochemical Surfactant FC-95 Acute Oral Toxicity (LDg,) Study in_Rats. 1978. Skin Irritation Report on Sample T-1117, 1974. Random Sample Assessment of Fluorochemical Serum Levels in Decatur Production Employees, 1998 Analysis for Fluorochemicals in 39 Individual Swedish Blood Blood Samples, 1999 Clinical Chemistries, Hematology and Hormones from Voluntary Medical SurveillanceofMale Fluorochemical Production Workers, 1995 and 1997 Evaluation of the Mutagenic Activity of T-6906 [N-E{FOSE alcohol] iMnoaunseInLVyimtrpohMoammamaCellilsan(WCiatlhl IGnedneepeMnudteanttioRnepTeeastt),Wi1t9h98L5187Y Mutagenicity Test on T-6292 [N-E(FOSE alcohol] in an In Vivo Mouse Micronucleus Assay, 1996 Mutagenicity Micronucleus Test on Assay, 1-5710 1993 [N-E{FOSE alcohol] in an In Vivo Rat VGietnrootoUxnisccihtyedTuelsetdoDn NT-A57S1y0n.t1he[sNis-EafnFdOCSeEllalPcroohloilf]eriantitohneAIsnsVaiyvoi/nin Rat Liver Cells, 1993 In Vitro Microbiological Compounds T-2247 CoC M[upteargfelunoircoiotcytyAlsssualyfsonoafte3DMECAomsaplta]naynd T- 2248 CoC, 1978 Salmonella- Escherichia ColyMammalian-Microsome Reverse Mutation Assay with PFOS, 1999 Salmonella Typhmurium Spot Test on FC-95 [PFOS], 1977 Bacterial Reverse Mutation Test of (x-1, 1996 ] Dra" nlAssn rRepeops dei V v* 000195 RSIS RSTO RS20 RSZ3 RS24 RS25 RS26 Mutagenicity Evaluation ofT-2014 CoC [PFOS] in the Ames Salmonella/Microsome Plate Test, 1978 Mutagenicity Test on T6295 [PFOS] in an In Vivo Mouse Micronucleus Assay, 1996 Unscheduled DNA Synthesis in Rat Liver Primary Cell Cultures with PFOS, 1999 Chromosomal Aberrations in Human Whole Blood Lymphocytes with PFOS, 1999 Evaluation of the Mutagenic Activity of T-5874 [N-MeFOSE alcohol] in the Ames Salmonella/microsome test (with independent repeat), 1994 Evaluation of the abilityofT-5874 [N-MeFOSE alcohol] to Induce Chromosome Aberrations in Cultured Peripheral Human Lymphocytes, 1994 Evaluation of the Mutagenic Activity of T-5874 [MeFOSE alcohol] in an In Vitro Mammalian Call Gene Mutation Test With LS187Y | Mouse Lymphoma, 1994 Mutagenicity Test on T-5711 [N-MeFOSE alcohol] in an Zn Vivo Rat Micronucleus Assay, 1993 Genotoxicity Test on T-5711.1 [N-MleFOSE alcohol] in the In Vivo/in Vitro Unscheduled DNA Synthesis and Cell Proliferation Assays in Rat Liver Cells, 1993 RS29 RS3T RS3Z RS33 RS34 'RRSS336S RS37 RS38 Analysis of Pooled Blood Samples from 3 European Blood Banks Analysis of Pooled Blood Samples from 18 U.S. Blood Banks `Analysis of PFOS from Pooled SerumofTwo Commercial Laboratories, 1998 APilot Study to Identify Fluorochemicals in Children With Limited Sera for Analysis, 1999 2Po6t-aWseseikumCaSpalstul(ePFTOoxSi;ciTt6y2S9t5u)diyn wCiytnhoPmeorlfgluusorMooocntkaenyesS.uUlfnoanuidciAtceiddDraft Final Report Two Year Oral (Diet) Toxicity Carcinogenicity Study of Fluorochemical FM-3924 [N-EtFOSE alcohol] in Rats 4-Week Capsule Toxicity Study with Perfluoroctane Sulfonic Acid Potassium Salt (PFOS; T-6295) in Cynomolgus Monkeys. Unaudited Draft. 1998. Second ninety-day rhesus monkey toxicity study [PFOS], 1978 Ninety day study in rats, [PFOS], 1978 13-Week Dietary Toxicity Study with N-Methyl raf niasxe Report Appenis va 000196 RS39 104-Week Dietary Chronic Toxicity and Carcinogenicity Study with Perfluorooctane Sulfonic Acid Potassium Salt (PFOS: T-6295) in [RS$0_TORraatsl.DeSvuemlmoapmreyntReaploTorxticWieteykSt5u3dyof N-EFOSEfnRabbits | RS41 Oral Teratology Study of FM3422 in Rats - Experiment No. RSE: 0680TR0010 [N-EtFOSE] RS43 Combined Oral (Gavage) Fertility, Developmental and Perinatal/Postnatal Reproduction Toxicity Study of N-EtFOSE in Rats 3M 418-009; Argus Research Laboratories Study Number: 6295.9, 1999 RS44 Oral (Stomach Tube) Developmental Toxicity Study of PFOS in Rabbits - 3M T-6295.10, Argus Research Laboratories Study Number: 418-012, 1999 RS45 Oral Teratology Study of FC-95 in Rats - Experiment No. 0680TR0008 RS46 RS47 RSE Rat Teratology Study T-3351 Final Report -- Project No. 154-160 `Combined Oral (Gavage) Fertility, Developmental and | Perinatal/Postnatal Reproduction Toxicity Study of PFOS in Rats Argus Research Laboratories Study Number: 6295.9, 1999. Protocol 418-008 RS49 Ninety day subacute rat toxicity study on FM-3422 [N-EtFOSE alcohol] RS51 Ninety Day Subacute Rhesus Monkey Toxicity Study on FM-3422 IN- EtFOSE alcohol] 104-Week Dietary Carcinogenicity Study with Narrow Range (98.1%) N-Ethyl-Perfluorooctanesulfonamido Ethanol in Rats. SUMMARY REORT - WEEK 53 Oral (Gavage) Pharmacokinetic Recovery Study of PFOS in Rats (1999) RS53 Determination of Serum Half-Livesof Perfluorooctanesulfonate and Other Fluorochemicals | RS54 28-Day Percutaneous Absorption Study with FC-95 in Albino Rabbits (1981) rttr rt w 000197 [RRS5S6S RS57 RSS8 RS59 RS60 O`rAabsloTreprtaiotnolaongdySbtioutdryaonsffTo-rm2a9t9i9oCnooCfiNn-REatbFbOiStEs and tissue | distribution and elimination of carbon-14 after administration of N- EtFOSE-"C in feed (1983) Extent and Route of Excretion and Tissue Distribution of Total (1979) Cholestyramine-Enhanced Fecal Elimination of Carbon-14 in Rats after Administration of Ammonium [14C]Perfluorooctanoate or Potassium [14C]Perfluorooctanesulfonate (1984) Analytical Laboratory Report on the Determination of the Presence and Concentration of Potassium Perfluorooctanesulfonate (CAS Number: 2795-39-3) in the Serum and Liver of Sprague-Dawley Rats Exposed to PFOS via Gavage (1999) ref nia sss Report Appesic vs 000198 ROBUST SUMMARY - RS1 Title: Eye Imitation Report on Sample T-1117. 1974 TEST SUBSTANCE Identity: Potassium perfluorooctanesulfonate. Remarks: 3M Sample T-1117, FC-95 METHOD Note pHof test material: Not specified Method/Guideline followed: Not specified Test Type: in vivo Species/strain/cell type or line: RabbivAlbino Sex (males/females/both): Not specified Number of animals/sex/dose: 6/single dose `Total dose: Itis gram for solids, assumed to be and FC-95 is a 0.1 grampereye solid as sold) (the method specifies 0.1 mi for liquids and 0.1 Lmeetnhgotdh,oifttiismaesstuemstedmattheatritahle misatienrciaolntwaacst winitcohnatancitmaflocreolnle: hoBuars,edalotnhotuhgehdtehsicsriisptniootnospfetcihfeied. Observation period: Ihr, 24 hr, 48 hr, 72 hr Sacccoorridnigngmetoththoedsucsaleedo:fsNcootrsipnegciffoireddaomrargeefetroentcheedco-m"eTah,eirrse,acatnidontthoe tbhuelbtaesrtamnadteprailaplebwraasl read conjunctiva..." gRreammarokfst:heRtaesbtbistusbswtearneceplwaacsedinisnticlolleldarins osnoetheeyey,ctohueldotnhoetrreuybetwheaisr eleyfetsu.ntErietahteerd0a.s1 amclonotrro0l..1 SthiencceonFcCe-nt9r5atiisoanosfoltihdemastoelruitailo,nitisisnoatssspuemceifdietdh.at T0.h1egmreatmhowdascailnlsstiflolerd.rem1o0v.i1ngmlanwyarsesinisdtuielloedf, athsestuemsetdmattheartitahleactocnatcachtopbesreirovdatwiaosn poenreiohdo.urS;ianlctehtohueghficrsotnotabcsterpveartiioodnipsenroitodotihseartwoinsee hspoeucri,fiietdi.s cIotmsear,epiorrist,edantdhatthtehbeurlebaacrtiaonndtpoatlhpeebtreastl mcaotnejruinacltiwvaaseraetad1, a2g4a,i4n8s,t aansdca7l2e ohfoudrasmaafgteerttoretahtement. T9.h3e3sacta2le4chroituerrsiaaafreerntorteaptrmeesnetnttehdenordercefreeraesnecdedo.veIrt tahpepereasrtsoftthahtescsotruedsyrteoazcehreod aatmtahex7i2muhomurof observation. The authors conclude only T-1117 is irritating to the eyes. -------- ve 000199 RESULTS Corrosive: no Irritation score: Only total scores provided. One hr: 8.00; 24 hr: 9.33; 48 hr: 3.33; 72 hr: 0.0. `Tool used to assess score: Not specified Description of lesions: none Remarks: over time. Inadequate description and discussion in report. Scores appear reduced in all rabbits ICnOaNdeCqLuaUtSeIiOnfNoSrma-tOinolnyiscpornecsleunstieodn ipnrorvepiodretdtionesvtaulduyaties qtuhaatlitteysot fsusbtsutdayncaendisviarlriidtiattiynogfto eyes. conclusion. REFERENCE J. A. Biesemeier and Project No. 4102871, D.L. Harris. 1974. Eye WARF Institute Inc. and Skin Iritation Report on Sample T-1117. raf nasre Report Appentc va 00ITH0 ROBUST SUMMARY - RS2 Title: An Acute Inhalation Toxicity Studyof T-2306 CoC in the Rat. 1979 TEST SUBSTANCE Identity: Potassium Perfluorooctylsulfonate. CAS No.: 2795-39-3 Remarks: Dust, PFOS (T-2306 CoC) METHOD Method/guideline followed: Similar to OECD 403 GLP: N, 10 QA/QC indicated Year study performed: 1979 Species/Strain: RavSprague-Dawley Sex (Males/females/both): Both No. of animals/sex/dose: S/sex/group Route ofAdministration: Inhalation Remarks: Concentrations of 1.89, administered to eight test groups. A 2.86, 4.88, 6.49, 7.05, 13.9, 24.09, Wright dust-feed mechanism with 45.97 mg/l dry air at a PFOS were flow rate of 12 T10he16telsittegrrsopuepr rmaitnsuwteeiwgahesdu2s0ed1-t2o9a9dmgiantisstteurdythieniPtiFaOtiSon.duTsth.e cRoanttsrowlergeroeuxpporastesdwefoirgh1 ehdou2r0.3- m2i6n3utgea.t sAtlludoythineirtipartoiotno.colTshewecroenttrhoelsraatmsewaesretheextpesotsgerotuopdrrayts.airTahtae rfaltoswwerartee oobfs1e2rvleitderfsorper farbnoomrtmhaelesxipgonssuprreiocrhatmobeexrp,oshuoruer,lyatfo1r5-fmoiunruhtoeurisntaefrtvearlsexdpuorsiunrget,haendI-dhaoiulryetxhpeorseuarfiee,raftorre1m4ovdaayls. Individual 7, and Day b14o.dytwiesigrhetpsorwteerdethraetcoalrldaendiomnalDsadyyi0n(gprsipoornttoanecxopuossluryew)e,rDeanyec1r,oDpasyie2d,aDsasyoo4n, Day as possible analyses after were death. Blood not provided. samples were collected on Day 14 from all surviving animals, but RESULTS LCS0=5.2 (4.4 ~ 6.4) mg/L; referenced methodofLitchfield and Wilcoxon Numberof deaths at each dose level (by sex): 70..005mgm/gl/:l:0/81/01;0;12.849.0m9g/mlg:/l0:/1100;/21.00(6amutgh:ors1d/i1d0;no4t.8p8romvgi/ld:e s2/u1m0;ma6r.4y9bmyg/sle:x)8/10; tReermmainraktse:d oTnheDahyig2h.esAttdotshaetgprooiuntp,, o4n5l.y97$ magn/ilm,awlsassunrovtiuvesdedanindtbhleoLodCs,acmapllceuslawteironestaankden at Dra nialsss Report Appeic va ee 000201 tperrombilneatmidonu.rinTgheexp1o3s.u9rmeg./lTghreosuepawniamsalalsswoetreermailnsaotneodteuasrleyd (iDn atyhe1L) Cb,e,caduetseermoifnaatmieocnh.anical In the 24.09 mg/l exposure group, 80% mortality. At4.88, 2.86, and all animals died 1.89 mg/l there by Day 6. was 20%, At 7.05 10%, and and 0% 6.49 mg/l morality, there was mraetsepercitailvealryo.unTdhteherantsosien oalrlotthheesrengarsoaulpdsisschhoawrgeed,syieglnlsoowfmtaotxeirciiatly airncoluunddintgheemaanocgieantiitoanl, rreegdion, dobrsyerravlaetsioornsotwheerrebrreepaotrhtiendgtdoisbteurlbeasnscferse,qaunendtgiennetrhaellpoowoerr ceoxnpdoistuiroen.grAobupnso.rmal in-lfe `Twhaes amlossotocbsoemrmveodnianbcnoonrtmraollirtaytswaansddtihsecroelfoorraetimoanoyfntohtebleivterreaatnmdenlutngr.elaDtieds,coTlhoerraetfioornoe,ftthheemlousngt. sAimgnoinfigcaanntitmraelastmtehnatt-direedlaptreedmaabtnuorremlayl,idteycwraeassveadrbyoidngy dweegirgehe,sofdidsicsocloolroatriaotnioofnotfhtehleunlgi,vear.nd discoloration and distention of the small intestine were also observed. CONCLUSIONS LC50=52 (4.46.4) mg. Only conclusion provided; seems reasonable with available data REFERENCE R2u3s0c6hC,oGCM.in,tWh.eER.at.RinPcrhoajretctaNnod.C.7A8.-7B1o8z5a,kB.io19/7d9y.naAmnicAscuIntce. Inhalation Toxicity Study ofT- OTHER - Summary modified 8/11/00 ---------- vo 000202 ROBUST SUMMARY - RS3 Title: 1978. Fluorad Fluorochemical Surfactant FC-95 Acute Oral Toxicity (LD) Study in Rats. TEST SUBSTANCE Identity: Potassium perfluorooctylsulfonate, CAS No.: 2795-39-3 Remarks: Fluorad Fluorochemical Surfactant, FC-95, White powder METHOD Method/guideline followed: Similar to OECD 401 GLP (Y/N): N, no QA/QC indicated Year study performed: 1978 Species/Strain: Rat/Charles River CD Sex (Males/females/both): both Number of animals/sex/dose: S/sex/dose Vehicle: 20% acetone/80% corn oil Route of Administration: gavage aRdemmianrisktse:redLeavsevlsoloufm1e0s0,of21150,mi46/4k,g abnoddy10w0ei0gmhtg./kTghePFraOtSs wweeirgehteedste1d7.2-A2l1l2dgosaet tlheeveblesgwienrneing oaftsthweesrteuodybsiemrmveeddiafotrelaybnporrimaotlro sdiognssindgurainndgwtehieghfotusrwheoruersreacftoerrdeedxpaotsDuraey, 7anadnddaDialyyth1e4,reTafhieer for 14 days. It is reported as all rats that survived to tthheateanldloafnitmhaels14d-ydianygsstupdoyn.tancously were grossly necropsied, as well RESULTS - LDS0: 251 (199-318) mg/kg, 3 references for statistical tables are given. Numberof deaths at each dose level (by sex): 100 mg/kg: 0/5 males, 0/5 females; 215 mg/kg: 2/5 males, 1/S females; 1000 mg/kg: 5/5 males, 5/5 females 464 mg/kg: 5/5 males, 5/5 females; Remarks: Al rats in raf nia ssssmens Report the 464 and Append 1000 mg/kg dose groups died before the end of the study. vio 000203 fTrherqeueenatnliymoablsseirnvethdei2n1c5lumdegd/:khgygporaocutpivdiiteyd, pdreecmraetausreedlyl.imbIttaopnep,eaarnsdsaitganxsioaf. tAotxinceictyrompossyt iorbrsietratviaotnoiofnsthiencglluadneddu:layremlulcowo-ssat,aiannedd luurnoggecnointgaelstrieogni.on,Nsotodmiaffcehrednicsetsenbteiotnweaenndsseixgenss owfere noted. LDS0 male rats: 233 (160-339) mg/kg LDSO female rats: 271 (200-369) mg/kg CONCLUSIONS - None specified beyond LDSO REFERENCE FDleuaonr,ocWh.Pe.m,icDa.lC.SuJrefsascutpa,ntG.FCT-h9o5mpAscounte, G. Romig, and D. Powell. 1978. Fluorad Oral Toxicity (LD) Study in Rats. Study No. 137-083, RIanttesrnwaittihonTa-l2R2e9s7eaCrocCh. aPnrdojDeecvteNloo.pm7e8n-t14C3o3rApo,rBatiioosne.arc(hI,ncIlnucd.e)s Acute Oral Toxicity Study in OTHER - Summary modified 8/11/00 rafniAsRsepore t Appn end ee var 00N204 ROBUST SUMMARY - RS4 Title: Skin Irritation Report on Sample T-1117. Identity: Potassium perfluorooctanesulfonate. Remarks: 3M Sample T-1117; FC-95 METHOD Note pH of test material: Not specified Method/Guideline followed: Not specified Test Type: in vivo Species/strain/cell type: Rabbits/albino Sex (males/females/both): Not specified Numberofanimals/sex/dose: 6 total Total dose: 0.5 grams per cachoftwo test sites per rabbit (intact-wet and abraded-wet) Vehicle: None Length of test material is in contact with animal/cell: 72 hr fGorramdaitinognsacanlde:edSecmaalefsoorfma1titoon4,aricncurseeadsianngdisncsoerveesriftoyr feoarcehryetndhpeomianatnadreessuchmamre(dcosmubcihnethda)t the. score equals the sum of erythema and edema scores. Reference source not provided. oRfeomnaerkgsr:amS(i0x.5almbii)nooftraebsbtitmsahteardiatlhewirashapirlaccleidppoendafbrroamdetdheoirrbianctkacst apnredpaflraendkst,esatnsditfeisve(itnetnactth-s wweetrearndemaobvreaddeda-nwdett)h,e dtehgerneceoovfeerreydtwhietmhagaaunzdeepdaetmcahewsaasndretcaopredde.d Aafctceorrd2i4nhgotuorsa stthaencdoavredriiznegds scale. An additional observation and scoring was performed at 72 hours RESULTS rReesdudletnsi:ngIonrasllweclalsiensgitdestercteepdo.rted the primary skin irritation scores were 0; which indicates no Primary irritation score: zero Remarks: No indicationofreliability. No QA/QC. No effects reported. Dra iedAsses Ror Append v2 00N205 CONCLUSIONS: No ofstudy and validityof irritation. Inadequate conclusion. information is presented in report to evaluate quality REFERENCE: JA. Biesemeicr and DL. Harris. 1975. Project No. 4102871, WARF Institute, Eye Inc. and Skin Irritation Report on Sample T-1117. Dfiil AsssRespomrt eAppnentd vas ceonee ROBUST SUMMARY - RSS Title: Retrospective Cohort Mortality Studyofthe 3M Decatur Plant, 1995 TEST SUBSTANCE Identity: PFOS Remarks: METHOD Study design: Retrospective cohort mortality study. AMlaanbuafmaac.turing/Processing/Use: 3M chemical and film manufacturing facility in Decatur, DHeycpaottuhrespilasnttewsatesd:sigTnoifdiecatnetrlmyidnieffwehreetnthefrrothmetmhoatrtwahliitcyhewxopuelridenbceeoexfpeecmtpedl.oyees at the 3M Study period: The cohort Decatur plant from March consistedofemployees who 1961 toDecember31, 1991 had worked at least one year at the Setting: Occupational. were physically distinct Plants entities located in Decatur, Alabama. The (approximately 300 yards apar). chemical plant and film plant Total population: 1957 employees were eligible for the cohort Subject selection criteria: day after March 1, 1961. Employed at least oneyear at the 3M Decatur plant and at least | `Total #of 1050 men esvuebrjeecmtpslionyestduidny:the1c6h3e9mmiaclaelspl(a7n0t deaths), 318 females (4 deaths) 1116 men ever employed in the film plant iCnoAmlpaabraimsaonwhpeorpeulmaotrieont:haUn.So. npeop-ulhaoatfiltohnf,e Acloaunbtaymawapsopwuiltahtiinon1,0a0nmdilthees poofpDuelcaattiuorn, ienxccoluundtiinegs counties in which there was a city with greater than 100,000 persons. wPaerrteicliosptattoiofnolrlatoew:-upVi(taalll smtaalteu)s.was determinedfor99.7%ofthe cohort. Only 6 employees ---------- vas N07 Subject description: `Total numberof person-years Numberof deaths Average age started work Average yearof entry Average age at death Average yearofdeath Still employed at plant Males 33,108 70 25 1971 a7 1984 81011639 Females 4,807 4 26 1977 2 1980 141318 Data from sctoaltleecvittiaolnstmaettishtoidcss:offMicoerst,alEiqtuyifdaaxtaDdeeartihveSdeafrrcohm,: National and TRW Death FAC+ Index, death certificates Summary. Work hfoirstaotrileesas(teomnpeloyyeaere. records) were used to verify that the employee worked at the Decatur plant Exposure period: Potential exposure period was March 1, 1961 to December 31, 1991 Description/delineation of exposure groups/categories: 1639 males, 70 deaths; 318 females, 4 deaths. eMmepalsouyreeddionrtheestcihmeamitceadledxeppoasrutrmee:nt(1s))e;v3e)r eevmeprleomypeldoiynetdheincthheemifcialml ddeeppaarrttmmeenntt((ss));; 42)) oonnllyy employed in the film department(s). Statistical methods: Program (OCMAP). SMR calculated using the Occupational 95% confidence intervals provided. Cohort Mortality Analysis Odetahtehrs smpeetchiofidcolfoorgitchealcaiunsfeoorfmdaetaitohn,: rSaceM,Rsexc,alacguel,ataenddutsiimneg(obbasseerdveodn tIoCDe-x8p)e.cteTdhenuemxbpeecrtoedf numberofdeaths was calculated the comparison population to the by applying cause-, person-years at risk. race-, sex-, age-, and time-specific rates Cohort members did not contribute for upeprwsoenr-eyecaornstruinbtuitletdhuenytihladdemateht, tlhoessmtionfiomlulomw-luepn,gtohrofthweoernkdocfrittehreiosnt.udyP.ersEomnp-lyoeyaeressofwefroellow washsoummeaddteoatbhe cwehrittifeicbaetceacuosuelndonoitnfboermoabttiaoinnewdaosnalvyawilearbeleinocnlurdaceed.inDetcheea"saleldcsatuusdeysomfedmebaetrhs" for and "unknown causeofdeath" categories. tShMeRUsScDoemaptuhtReadteussipnrgotghreamO.ccuRpeastulitosnawlerCeohvoirrttuMalolrytaildienttyicAanla.lyMsoirstaPlriotgyrraamteasnfdorcwohmiptaersewdertoe used to calculate the expected numbers for all men and women. rah iilAssn Ror ppesic V ee vas ocNzos RESULTS wDeerscersiibmeilraersutlo,tsb:utSlMoRwesr btahsane,d tohnostehebaAsleadboanmatahendUSAlcaobmapamraicsoounntpioepsulcaotmipona.riUssoinnpgoptuhleaUtiSonass the comparison population, SMR for men for all causesofdeath, heart disease, and respiratory. disease (nonmalignant) were significantly less than 100 (62.9, 59.1, and 0, respectively). The SMR for all cancers was 68.4, although not significant. Most ofthe specific cancer SMRs were less than 100 except for cancofethre bladder and other urinary organs and cancer ofother dleyamtphhsataincd awnedrehenmoattostpaotiiesttiiccaltliysssuieg.nifFiocarntt.hese 2 causes, the SMRs were based on only 1 or2 extemal causes, `There were only 4 deathsforwomen. When compared to the US population, no causeofdeath had an SMR significantly different from 100. Threeofthe 4 deaths were from non-work-related For men ever employed in the chemical department(s), the SMR for all causes wassignificantly less than 100 (48.8; 95% C1 24.4, 87.4). SMRs for all cancer were 76.9 (95%CI 40.9, 131.5). Although not statistically significant, SMRs > 100 were reported for men ever employed in the chemical department(s) (n = 1,050) for cancer ofthe `bronchus, trachea and lung [SMR = 120.7; 95% CI 48.5-248.7), cancerofthe bladder and other urinary organs [SMR = 415.5, 95% CI 10.4 - 2,315.3], aleukemia cancer [SMR ofthe brain and = 120.0, 95% CI o3t.h0e-r66C8.H8S],[aSnMd Rca=n1c1er7.o2fo,th9e%r CI 2.9 - 653.0], leukemia and lymphatic and hematopoietic tissue [SMR = 137.2, 95% CI 3.4-764. 5]. Allof these SMRs > 100, except for cancerofthe `bronchus findings , trachea and were reported lung, were basedon just when the analyses were one rest observed death. C ricted to men who omparablenonsignificant only worked in the chemical plant (n = 485). All of the above SMRs were based on the US comparison population. `There were 37 deaths among men ever `employed in the film department(s). Astatistically significant deficit was observed for all causesof death combined (58.6, 95% CI 41.3, 80.8). Eleven deaths were observed for men only employed in the film department(s). There were no statistically significant increases in SMRs for anyof the causesof death. sSutbujdeyctsstwreernegtohlsdearntdhawnea4k5neyesasress:of Fageewadtetahtehsen7d4o/f19s5t1u,dyo,nlfyeawpwproomxeinmactoeullyd4b5e%ostfudtiheeds,tluednygth o(fdoeemspnlootyamdednrteswsalsatneontcym,etausumroevde,r,PeFtcO.)S. serumlevels Onlyhalf of were not examined in relation to mortality the employees are still employed at the plant, This study has a very high rate offollow up for employees (97.3%), and will be updated in 2000. ERnevsieraorncmhenstpaolnsaonrds:OccUunpivaetrisointayloHfeaMlitnhn.esota, Schoolof Public Health, Division of Ort et sm eia.tenti vaog en209 Consistency of results: There are no other mortality worker studies on PFOS. CONCLUSIONS cAommopnargismaolnepso,pSulMaRtisonweurseedbetolocawlctuhleantuellthveaelxupeefcotreadllvamlaujeos.r cGaiuvseesnotfhdateatthehwroergakredrlepsospouflatthieon swmaasll50adydoiutniogn,alit aismodiufnfitcuolftitnofdorrmaawtimoann;yhocwoenvcelurs,ioonnsl.yhaAlnfoufptdahteeoefmptlhoeyseteusdayrweilsltiplreomvipdleoyaed at the plant, and PFOS-related products will soon be removed from the manufacturing site. REFERENCE Mandel JS and Johnson RA. March 13, 1995. Decatur, Alabama. University of Minnesota, Mortality studyofemployees Schoolof Public Health. at 3M plant in raf naAssos Report Appentic var oenzio ROBUST SUMMARY - RS6 Title: Random Sample Employees, 1998 Assessment of Fluorochemical Serum Levels in Decatur Production TEST SUBSTANCE Identity: PFOS Remarks: here. Other fluorochemicals were assayed in this study. However, only PFOS is reported METHOD Study design: Random, cross-sectional occupational study. Manufacturing/Processing/Use: employees. Comparisonofchemical plant employees to film plant dHeytpeortmhienseisthetedsitsetdr:ibTutoiornaonfdoemmlpylosyaemeplseereummplfolyueoersocfhreommictahlelDeeveclastuarcccohredmiincgaltopdleamntogtroaphics, vcuorlruennttarayndnaltounrgeeostf thheeldmjeodbisc,alyesaurrsvewiolrlkaendc,e parnodgbruaimlddiindgnlootcaptrioonvsi.deTfhiosarwcaosmpdloenteesince the understandingofthe distribution of fluorochemical serum levels in the Decatur workforce. Study period: October~ November 1998 Setting: Occupational--Decatur, Alabama. p`aTrottiaclippoatpeul(atottiaoln#:of23w2orekmeprlsoayteeplsarntanndotomplryovcihdoesde)n + 76 "volunteers who requested that they Subject selection Alabama. criteria: Current employment at thefilmor chemical plant in Decatur, `Total# of employees subjects in study: who volunteered to 186 employees participate. outof the random sample of 232, plus 76 Comparison population: N/A Participation rate: 80%ofthe random sample participated rat nial ssn Report Append vas 0031 Average age Chemicalplant employees 42 years old Avg. length of employment Gender 16 years mostly male Film plant employees 46 years old 19 years mostly male Data collection methods: Work history questionnaire and blood sera samples pDreotcaeidlusroen, danadtaPcFoOllSecwtiaosn:meSaesruaresadmupsliensgwheirghe-epxrtersascutreedluisqiuindgcahnroimona-tpoagirraipnhgye/xetlreaccttrioonspray tandem mass spectrometry evaluated versus an extracted curve, Exposure period: N/A Dreecsocrrdiepdticounr/rdeenltiannedatlioonngeosfte-hxeplodsure groups/categories: On questionnaire, employees jobs, age, BMI, hand-to-mouth activity. Measured or estimated exposure: PFOS serum level is surrogate for exposure Exposure levels: N/A sStiantgilsetaicnadl mmuelttihvoadrsi:ablUesreedgrSeAssSioanndusJinMgPlitnoecaralacnudlatneonsltiundeeanrta'nat-ltyesset,s.chGiesoqmueatrer,icANmeOaVnAs, tcahlecLulLaOteQd (alnodg0nowramsalusdeids.tributions). For serum values less than the LLOQ, a midpoint between `Oatnhdenronmreetshpoodnodleorgsiicnalrainndfoomrmsaatmipolne: bDyadtaemaongarlayspehsicwecrhaeraccotnedriuscttiecds;to2:) c1)ocmopmapraermeeraenspsoenrduemrs fluorochemical within the film levels within the chemical plant by similar factors. plant; 3) compare mean serum fluorochemical levels RESULTS Describe results: Chemical plant employees (n ppm (95% CI, 0.091 -- 10.600); geometric mean = 126): arithmetic mean PFOS level PFOS level was 0.941 ppm (95% CI, was 1.505 0.785 f1.r1o2m8)c.acMhaoltehe(r0..8O9n7 pavpemr)agaen,dsfeermuamlefl(u0o.r4o5c9hepmpimc)algleeovmeeltsrwiecrmeeaannsorwdeerreofsmiganginfiictaundtleyhdiigfhfeerrent amemaonngPcFhOeSmilceavlelpl=an0t.1e7m2plpopymee(s9t5h%anCIo,th0e.r01w5or~ke0r.s9.46F)i;lgmepolmaenttriecmpmleoayneePsF(OnS=l6e0v)e:l =ar0i.t1hm3e6tic ppm (95% CI, 0.114 -0.162). pRleasnutltjsobwecrateecgoormipeasrwaebrlee stotrtohnegleympalsosyoceieast'edsewlift-rhepprorotdeudctlioonngebsuti-lhdeilndgjoabsss.igCnumrernetnst.cAhreimtihcmaeltic [r-------- vas oenn12 cmaetaegnorsieersu(mraPnFgOe)Swleervee:lsce(lrlaonpgeeriantoprasre2n.t9h0e3sips)pmfo(r0.t3h2e5e-i6g.h8t40c)h;emwiacsatlepolpaenrtactuorrrsen2t.j6o4b9 ppm (4.00.6205)4;-7s.u8p8e0r);vicshoermsi/cmaalnaopgeermaetnotrs1.18.77981(0p.p0.m09(10-.1407.16-070.)2;60m)i;llmaopienrtaetnoarnsc0e.w7o1r8k(e0r.s2310.-627.204(00).;291engincer/laboratory workers 0.634 (0.095-1.740); and sccretarics 0.497 (0.220-1.140). PFOS was modestly positively associated ( = 0.11) with years worked in the chemical plant. Shatvuedyocscturrernegdthisn parnedviwoeuaskDneecsasteusr:stTuhdiisesstinudwyhaidcdhrepasrsteidcitphaetipoonsswiablsevvoolluuntnatreye.r biTahsisthsattucdoyuladlso measured other perfluorinated compounds in blood serum. `This study categories. did not provide exposure information, but did provide additional information on job Research sponsors: 3M Environmental Lab Consistency the voluntary of results: The distributionofserum medical surveillance programs. levels are consistent with those reported in CONCLUSIONS Balalsoewdedonfaoarrabnedttoemr suanmdperlseotafnedmipnlgooyfetehse,dtishterdiabuttaioonbotafinseedvefnrofmlutohrioscbhieomliocgailcsalinastsheescshmeemnitcal oabnsdefrivlemdpwlearnte ecmopmlpoayreaeblpeoptuoltahtoisoensre(poonrltyedPFinOtSherevpoolrutnetdarhyerme)e.dicDailstrsiubruvteiiolnloanfcseeprruogmrasmasm.ples REFERENCE O1l1s,e1n99G9,.LFolguaonroPcWh,emSiicamlpseoxnpoCsAur,eBausrrsiesssJmMe,ntBoufrlDeewcaJtMu,r cShcehmuimcpaelrtanJdC,fiMlamnpdlealntJeH.mplAouygeuesst. 3M Medical Department, St. Paul, MN. FYI-0500-01378. OTHER er Wong ROBUST SUMMARY - RS7 Title: Analysis for Fluorochemicals in 39 Individual Swedish Blood Blood Samples, 1999 TEST SUBSTANCE Identity: PFOS Remarks: METHOD Study design: Cross-sectionaldataon Swedish disease laboratory. PFOS detected in individual serum samples from a Manufacturing/Processing/Use: N/A Hypothesis population. tested: To determine the presence of PFOS in the serum of the general Study period: 1998 Setting: N/A `Total population: Provided 39 information was also provided. individual Swedish samples. Age and gender demographic Subject selection criteria: At discretion of the Swedish disease laboratory. `Total #of subjects in study: 39 Comparison population: N/A Participation rate: N/A 8Su6byjeeacrts doefsacgrei.ptOionnl:y 3Thsearmeplweesrewe1r6emuanldeesratnhde 2a3gefoemfal1e7s.(agAegse5,r5anagnedd 1f2r).omM5etahnrough age was 42. Health effects studied: PFOS levels in blood Data collection methods: Blood scra samples Details drawn, on data collection: stored, etc No information was provided as to how the blood was Dra nilsesRepsort Append vai oonzia Exposure period: Unknown--PFOS serum levels used as surrogate for exposure. Description/delineation of exposure groups/categories: N/A Measured or estimated exposure: N/A Exposure levels: N/A Statistical methods: Means calculated. Other methodological information: RESULTS DLeoswcerribLeimrietsoulftsQ:uaAnttiottaatlioofn2(8L(L7O2Q%))owfhitchhe w3a9sin3d1i.v4idpupabl.s ThahdesmceraunmsPcFrOuSm PleFvOelSs lbeevleolwfotrhethe T1h1eirnediwveirdeuanlos wsihgonsifeicsaenrtudmemleovgerlaspwheircedaibffoevreentcheesLbLetOwQeewnaisn4di8v.i0dupaplbs(wrhaonghea3d1.L6L-8O5Q.4vpeprbs)u.s tPheorsceenwthmoasleesweerruem3P9FaOnSd v4a5lupeerscwenetr,er>esLpeLctOiQve.ly.AveArmaogengagtehsosweeriend4i0viadnuadls43w,hroeshpeacdtisveerluy.m PFOS values greater than the LLOQ, there was no association with age and/or gender. SintituidalyPsFtrOeSngltehvselainndtwheeagkenneersaslesp:opulTahteisoen-d-antoaoatrheercrdoesssc-rsiepcttiivoenailnfdoartmaautsieodn taoboduettetrhmeisnuebjaencts twhaasn cLoLllOeQc.ted.BlLoiomditdeodnonrusmcbaenrnooftsbaemcpolnessidaenrdedferweeprreyseetnttahtaitvheoafdtsheerugmenPerFaOlSpolpeuvlealtsigorne.ater Research sponsors: 3M Medical Department Consistency of results: N/A CONCLUSIONS NA rat niassessmens Report Append var 00ONT1S ROBUST SUMMARY - RS8 MTiatllee:FlCulionrioccahleCmhiecmailstPrrioedsu,ctHieomnaWtoorlkoegrys,an1d9H95oramnodn1e9s97from Voluntary Medical Surveillance of TEST SUBSTANCE Remarks: METHOD Study design: Cross-sectional Manufacturing/Processing/Use: Facilities in Decatur, manufacture perfluorooctanesulfony! fluoride products. Alabama and Antwerp, These fluorochemicals Belgium which can metabolize in the body to PFOS. aHnydpohtohremsoinsaltesptaerda:metTeorsprionviredleatainonagtgorseegratuem aPnFalOySsisloevfeltsheashemmeaatsoulroegdy,inctlihneimcaeldiccheamlistries, surveillance examinationsofAntwerp and Decatur employes in 1995 and 1997. Study period: Fall 1994 to Spring 1995, and 1997 Setting: Occupational. Plants located in Antwerp, Belgium and Decatur, Alabama eTomtpalloypeoepsulwaetrieone:ligAipblperofxorimtahteesltuydy3.00TDheecattotuarl epmlapnltoypoepeuslaatnidon2s00weArnetwnoetrpprporvioddeudc.tion S1u9b9j7e--cotnsleylemctailoenscwreitreeriaan:alVyozleudnbteacrayupsaerotfiscimpaaltilonniunmbmeedriocfalfesmuravleeilwloarnkceersp.rogram 1995 and TTohtearle #waosf aslusbojeactssubisnetsotfudey:mplIony1e9e9s5,fo9r0wDheocamtuhroramnodn8a8l Apnartawmeertperesmwpleoryeesetsudpiaerdt:ici5p0a/t8e8d. Antwerp and 38/90 Decatur employees. In 1997, 84 Decatur and 65 Antwerp employees volunteered in the medical surveillance program. Comparison population: N/A pPaarrttiicciippaatteidoinnrtahtees:e vIonlbuonttharyyeamresd,icleasls stuhravnei5l0la%ncoefetxhaemeilniagtiibolensp.roOdnucltyi6o1n eemmppllooyyeeeess were `common to both time periodsofthe study. ISnudbejxectthadnestchreipAtnitowne:rDpeecamtpulroeymepsloiynebeosthwe1r9e95siagnndifi1c9a9n7t.lyAonldtewreapnedmhpaldoyaeheisghaelsroBsomdoykMeadslsess less (1995) than Decatur employees, consumed more alcohol, and had significantly different (p fr -- vas 00216 (<l.o0w0e1r)),meHaDnLm(ehaisguherre)m,etnrtisgolyfcaelrkidaelsin(elopwheor)s,phaantdasMeC(HloCwera)c,rotsotsalbobtihlitriubmienp(ehriigohdes,r), glucose bHaesaeldthonefifneccrtseasstiundgiPedF:OTSoledveetlesr:mihneemiaftothleorgeyw(ehreemadtiofcfreirte,ncheesmoingltohbeifno,llRoBwCisn,g pWaBraCme,teprlsatelet acomuinnto)t,racnlsinfiecraalsec,heamliasntirnieesam(ianloktarlainnesfpehroasspeh,attoatsael,agndamdimraectglbuitliarmuyb!int,rbanlsofoedrausre,eaasnpiatrrtoagteen, tcrriegaltyicneirnied,esg)l,ucaonsde,hochromloenstaelropla,rlamoewtedernss(ictoyrtliispoolp,rdoetehiyndsr,oheipgihanddernossitteyrloinpeopsruoltfeaitnes,,esatnrdadiol, hfoolrlimcolenestbiimnudliantigngglohbourlmionn,er,ee17t-easltpohsatehryodner,oxbyopurnogdetsetsetroosnteer,onleu,teainndizitnhgyrhooirdmsotniem,ulpartoilnagctin, sex wDeaitgahtc,olalnedctbiloonomdeptrheosdssu:re, Maenddicsatlanqduaersdticolinnniaciarle,chbelmoiosdtrsyeraansdamhpelmeast,olmoegaysutresetms,enatnsd opfulhemiognhat,ry iDnetraeipolrst.onDdaattaaocnolblleocotdiocno:llQeucetisotnio(nanmaoiurnet,coenttee.n)tn,odtepsirgonv,idaeddm.inistration, etc. was not provided MSienrnuemsoPtFaOuSsimnegahsiugrhe-dpeinrf1o9r9m5anbcye3liMq'usidEcnhvriormoantmeongtraalphTyecthhneromloosgpyrSaeyrmviacsesspiencSttr.omPeatulr,y. In p1e9r9f7,ortmhaensceerluimqusiadmcphlreosmwaetroegraanpahlyyzeeldecbtyroAspdrvaaynmcaesdsBsipoaencatlryotmiectarlyServices, Inc. using high- Exposure period: Unknown. PFOS serum levels are surrogates for exposure. Description/delineation of workers' sera were grouped exposure groups/categories: for cach plant as: 0 <I ppm; The PFOS 1- <3 ppm; levels detected in 3 - < 6 ppm; >= 6 ppm PFOS. Distributionof Employees by Year andPFOS levels 1995: Antwerp (n = 88 39%<I0pp-m PFOS 36%1-<3ppm PFOS 22% 3-<6ppm 3% >6 p=pm 1995: Decatur (n = 90) 12%0-<1 ppm PFOS 66%1-<3ppm PFOS 18% 3-<6ppm 4% >=6 ppm 1997: Antwerp (n = 65 48% 0-<1 ppm PFOS 38% 1-<3 ppm PFOS 14% 3-<6ppm 0>=6 ppm [---------- 1997: Decatur (n =84) 35% 0-<I ppm PFOS 45% 1-<3 ppm PFOS 14% 3-<6ppm 6%>=6 ppm vas onnnay Measured or estimated exposure: Serum PFOS levels are surrogates for exposure. No worker exposure data are available. Statistical methods: analysisofvariance, Descriptive simple and stratified and multivariable regression used analyses, Pearson correlatiocnoefficients, to evaluate associations between PFOS and each hematological and clinical chemistry test and hormonal assay. alcohol consumption, and cigarette use as potential confounders. Adjusted for age, BMI, Other methodological information: RESULTS Describe results: 0-<1ppm 1-<3ppm 3-<6 ppm 2 6 ppm Distribution of Serum PFOS 1995 1997 Antwerp 34 Decatur 11 Antwerp 31 32 59 25 19 16 21 3 4 0 Decatur 29 38 12 5 In 1995 for both locations combined, PFOS was. significantly (p<.05) correlated with HDL (negative association), total bilirubin (negative), WBC (positive) and platelets (negative ). In (1p9o9si7tifvoer),boatlhanlionceataimoinnsotcroamnbsifneerda,seP(FpOosSitwivaes),sidginriefcticbainltilryubcionrr(enleagtaetdivwei)t,hcahoglees(ptoesriotliv(ep)o,siBtiMvIe), LDL (positive) and hematocrit (negative). The means of the 4 PFOS categories combined across both plants were all significantly different from each other. The youngest employees had the lowest PFOS levels. Ofall of the clinical chemistries and hematological parameters, only total bilirubin had significant (p<.05) differences in means from the lowest exposure category (0 - <1 ppm) for both years. The lowest mean platelet count was observed at the highest PFOS exposure category in both years, although they were not significantly different across categories. Using linear regression and adjusting for potential confounders, PFOS was significantly (p<.10) associated in both years only for total bilirubin. In oneofthe 2 years, PFOS was associated with direct `These bilirubin creatinine, variables were then cholesterol, LDL, separated by plant HDL, hematocrit, location and year. hemoglobin, and platelet Only total bilirubin and count. HDL were significantly (negatively) associated with PFOS for at least one plant location for both time inpebroitohdsy.eaTrostaalndbinloirsuibginnifhiacdanat saisgsnoicfiiactainotnneatgatthievAenatswseocripatpiloanntwiftorh cPiFthOerSyfeoarr.theHDDeLcawtausrplant significantly negatively associated with PFOS in Antwerp in both years but not significantly associated with PFOS in Decatur in either year. Dra tidtsssmes Bepor- Append V vas c0d218 `There was the serum no evidenceof a levels measured. dTehcelionveerianlslelreuvmelcshboeletswteeernolpalsanstosciaantdedowvietrhboatnhiynecarreassweeirnePnOotS at statistically significant. Cholesterol levels by PFOS serum levels are presented below. Serum Cholesterol Levels by Plant and Year 0-<ippm 1-<3ppm 3-<6ppm 26pm 1995 Antwerp 220 206 217 223 F=06 p=06 Decatur 215 21 209 206 F=05 p=07 0-<ippm 1-<3ppm 3-<6ppm 26pm 1997 Antwerp 192 213 228 228 F=29 p=01 Decatur 204 218 20 29 F=20 p=01 eSmixptlyo-yoeneesewmapslolyoeweesrptahratnictihpaatteodf itnhebi1o9m9o5nietmoprlionygeefosrabnodthhiygeahresr. thTahnethmaetaonfathgee 1of99t7hese eTmwpelnotyye-esse.veCnhoolfetshteer6o1leamnpdlLoyDeLeswweerreesifgrnoimfitchanetAlynthwieghreprpilnantth.e 6T1hepsaerteimcipplaonytseeisn h19a9d7. shiiggnhiefriccahnotlleystheirgohlervamleuaesntPhFanOtSheexApnotswuerersp,pwaertriecispiagnntisfiicnan1t9l9y7o.ldReer,gahraddlegsrseoatfeprlBanMtIsloacantdion, `mean PFOS levels were measurements in 1995. higher for those employees who were selected for hormone Thihgehemsetaenxpaogseuroef tchaetelgoowreys;ttPheFreOfSoree,xpmoesaurneDcHatEeAgSor,y (107--<HP,1)fwicaeste1s0toysetaerrsonleesasntdhabnouthnadt of the etxesptoossutreerocnaetelgeovreilzsaattiotnhse.thAidsjeuxsptoisnugreforletvheel dwiefrfeergernecaetserinthaagne t(haecmoenafonusnodferthfeorhimgahleer PFOS tsiegsntiofsitcearnotneashsoocrimaotnioenslebveeltsw)eaenndPoFthOeSr caonndfothuendheorrsmoinnetshearneaglryezsesdi,onexmcoedpetlfsorreessutlrtaeddioiln no However, (3 when one employee with 12.83 ppm PFOS serum level, confounded by a high BMI kg/m?) was excluded from the analysis, the finding was no longer significant. -------- vas 0219 Study strengths and weaknesses: Cross-sectional design, voluntary participation, small bnoutmhbteirmoefpeemrpioldosy.eTehserwiewthasPFaOlSarlgeevetlusmaobvoevrer6atpepbme,twleoewnptahreti2cisptautdiyonyeraatres i(nonbloyth61pleamntpsloiynees `ancdomtmhoeny atlosbooctahnnsottudbyepecroinosdis)d.ereTdhienddaetpaenwdeernetcpoompublianteidonsa.croTshse2sseirteusmthlaetvewlesroefvPeFrOySdimffaeryenbte,. bNeoloocwctuhpeatnioo-ncaflfeecxtploesvuelreindaltaabwaenrimeaclosl.leSceterdumatPeiFtOheSr mplaanyt.not accurately reflect body burden. `This study provides data on PFOS serum levels and biological parameters not studied before, and provides a comparisonofthese data across plants Research sponsors: 3M Consistency of results: Thereare no other studiesof thiskind on PFOS; however, the results of the hepatic Burris JM, and lipid clinical chemistry tests have been published. The reference is: Mandel JH, Zobel LR Serum Perfluorooctane sulfonate and hepatic and Olsen GW, lipid clinical chemistry tests in fluorochemical production employees. JOEM. Sept. 1999;41:799-806. CONCLUSIONS `The authors concluded that among Antwerp and Decatur male employees, significant hematological, clinical chemistry and hormonal abnormalities were not associated with scrum PFOS concentrations less than 6 ppm. RinEveFsEtiRgaEtNioCnoEfcOllisneincaGlWc,hemBiusrtrriisesJ.M,HeMmaantdoelloJgHy,aZnodbehlorLmR.oneAspriinlr2e2l,ati1o9n98t.o sAenruempildeevmelisoloofgic perfluorooctane sulfonate in male fluorochemical production employees. 3M Medical Department. FYI-0300-01378. OTHER There are several methodological issues that should be noted. They are: 1) Cross-sectional association. design does not allow for a direct analysisofthe temporality ofan 2) The voluntary participation. participation rates were low as both production sites had less than 50% 3) Gbiiovleongitchael saucscpoemcmteoddaltoinognhatlof-tlhiefeeofffecPtFsOoSf,PiFt OmSaywhbiecchonwcoeuilvdabmlientihmaitztehetrheempaosysibbeilsitoyme of finding an association 4) Serum PFOS measurements may reflect body burden. In the cynomolgus primate, liver tdiossseuegrcoounpcse)n.traHtoiwoenvsearp,prinoxtihmeartate,dtshiesruramtiPoFwOaSs ilnevtehlesruapngtoe o1f003:p1p1m0 6(:l1o.w- and mid- 5) Temhpel2oycereosssw-seercetisotnuadlieadnailnysbeosthcaynenaorts (bdeuveiteoweladrgaes tiunmdoevpeenrdbeenttwpeoepnulsattuidoynsyeaasrs6)1. 6) 7) TThheerpeuclsoautlidlebneamtueraesoufrseommenet oefrrtohre ihnoirmmpoonretsansttcudoinefdouhnadsirnegsuvlatreidabilnesp.rior recommendations that mean hormone measurements should be the resultofpooled blood from multiple samples taken at short intervals; however, this was not feasible in this study. rat ntlsessmentReport Append V var 000220 ROBUST SUMMARY - RS9 Title: Serum Fluorochemical Levels in Sumitomo employees, 1999 TEST SUBSTANCE Identity: PFOS Remarks: METHOD Study design: Cross-sectional. Manufacturing/Processing/Use: Processing and formulation of fluorochemicals into products. Hypothesis tested: To determine PFOS serum levels in employees at the Sumitomo, Japan 3M Plant Study period: 3 weeks in March 1999 Setting: Occupational--Sumitomo 3M employees, Sagamihara Plant, Japan. Total population: Total numberofemployees working at this plant was not provided in the report. `Subject selection criteria: Voluntary participation in medical surveillance program at Sumitomo 3M Plant. Total #ofsubjects in study: 94 volunteers (managerial and production employees) Comparison population: Sagamihara plant management employees (n = 32) and management employees from the Tokyo Head Office (n = 30) Participation rate: Not provided. Subject description: Across all 3 "exposure groups", the age range was 31 ~ 67 years old. No other information was provided. Health effects studied: PFOS levels in blood Data collection methods: Blood sera samples Details on data collection: Sera was analyzed for fluorochemicals using high-pressure, liquid chromatography/clectrospray tandem mass spectrometry. The LLOQ for PFOS was 0.0314 ppm. rot iil Assam Report ppendc vas conz21 Exposure period: N/A eDmespclroiypeteison(/nd=el3i2n)e;atSiaognaomfiehxarpaosure groups/eategories: Sagamihara Plant production p3l0a)n,t4m0ankamgefmreomntSaegmapmliohyaereas P(lna=nt32); Management employees from Tokyo Head Office (n = Measured or estimated exposure: PFOS serum level is surrogate for exposure Statistical methods: those employees with Descriptive values less statistics and t-tests than the LLOQ) (calculated using the LLOQ value for Other methodological information: RESULTS 3De8s%corfibteherepslualntts:ma2n4aogfem94enetmpelmopyleoeyseehsadhasdersuemrulmevleelvsel<sL<LLOQL.OQ, and 40%ofTokyo office, PFOS was quantifiable in all production employees. Sagamihara Plant production 0.0475-0.628 ppm. employees: arithmetic mean PFOS level = 0.135 ppm, range Sagamihara ppb Plant management employees: arithmetic mean PFOS 40.3 ppb, range 31.9- 56.6 Management 96.7 ppb employees from Tokyo Head Office: arithmetic mean PFOS 52.3 ppb, range 33 -- `The arithmetic mean (0.135 for both managers' groups. ppm) was significantly different (p<.05) than the mean PFOS value Study strengths and weaknesses: information on the employees. No information on exposure in the workplace, no descriptive Research sponsors: 3M Consistency of results: No other processing employees have been sampled. CONCLUSIONS wTehreeabuetlhoowrstchoosnecolfudweodrktheartssaetrtuhmeP3FMOSAnltewveelrsopfanSdagDaemciahtuarraplPalntasn.t production employees REFERENCE FBulruroirsocJ,heOmlisceanlGLWev,elMsanindeSlumJiHt,oSmcohu3mMpeErmtpJlCo.yeSeesp,tFeimnbaelrRe3,po1r9t9,9.3MDeMteedrimcianlatDieopnaorftmSeenrtu,m Epidemiology, 220-3W-05. FYL0500-01378, [---------- vas 000222 OTHER Ovanial Assessment Report Appendic van c00223 ROBUST SUMMARY - RS 10 TMiuttlaet:ioEnvaTleusattiWointohfLt5h1e8M7uYtaMgoenuisceALcytimvpithyoomfaT-Ce6l9l0s6(iWnitahn /InndVeipternodMeantmmReapleiaat)n,C1a9ll98Gene TEST SUBSTANCE Identity: T-6906; N-E{FOSE alcohol Remarks: "Creme coloured solids" purity 97%; Identification: T-6906 batch 040016. METHOD Method/guideline: L133 & L248 OECD Guideline 476; EEC Directive 67/548/EEC, EEC Publication No. `Test type: Reverse mutation assay Test System: Mammalian cell line GLP: Yes (OECD Principles of Good Laboratory Practice). Year study performed: 1998 Species/Strain: LS187Y mouse lymphoma cells. Metabolic activation: S9 from Aroclor-induced adult male Wistar rat liver added at 8% v/v. Statistical methods: None Remarks: Study Design: Concentration: Rangefinding test: 3, 10, 33, 100, 333, and 1000 g/ml with and without 9; Experiment 1: 10, 9; Experiment 2: 18, 10, 33 42, 56, 75 & 100 20, 30, 40, 45, 50 & ug/ml without $9; 33, 55 ug/ml without $9; 100, 333 & 10, 33, 100, 1000 175, pg/ml with 250, 375, 500 &750 pg/ml with 9 Numberofreplicates: 2 Platesest: two 96-well plates/concentration for plates/concentration for cloning efficiency mutation frequency (~2000 cells/well). (~1 celliwell; three 96-well Solvent: Dimethylsulfoxide (final concentration in culture medium not specified). Pwoistihtoiuvte ccaolnctiroulms:anWditmhaoguntes8i9:ume)t;hywlimtehtSh9a:nedsiumleftohnyaltnei(t1romsaMmiinne H(a0n.5k'ms MbalinanHcaendk'sasltbaslolauntcieodn,salt solution, without calcium and magnesium) RESULTS Cclyotnoitnogxiefcfciocinecnecnytratatainoyn:doIsner(atnegstefmiantdeirniagltepsrtewciiptihta$t9e,dnaot hriegdhuecsttiodnoswe)a.s sWcitehoinutce$ll9,ncuemllbecrouonrt #agn/dmlc.lonIinngExepfefriciimeenncty i1,mmweitdhioauttelSy9,afctoencternetartamteinotnsweorfe56reudgu/cmeld saingdnihfiigchaenrtlwyearte3"3t3ooantdoxi1c,0f0o0r further testing." In the presenceof$9, no severe toxicity was seen and all dose levels were rat itlsess Report Append vai oceozza wevearleua"t1e0d0 ftoorximcu"taagnedniicnitthye.prIenseexnpceeroifmeSn9t, 2c,onwcietnhtoruattiSo9n,scoofnc3e7n5traantdio5n0so0fji5g0/malnwder55e "gt/oomtoxic" and were not evaluated for mutagenicity. mGuetnaonttoxfirceqeufefencctys:wiNtoh Sin9crweaassesciennmuotnalnytatftrheequheingchyessteednosweitihnoeuxtpeS9r;imaenntap1p,abruetntthiinscwraesa.se in confounded by precipitation of test material no significant increase in mutant frequency (i.., unphysiological was seen without S9. conditions). In Slight increases experiment in mutant 2, mfarteeqruieanlcpyraetci7p5i0taatinodn 2a5t 075p0g/umgl/m(lnoatnddosaen-parboeprorratntiodnoasle)-wrietshpoSn9sewecrurevaelsfoorcsounrfvoiuvanlde(dsebeytatbelset). ARletmhaorukgsh:thAe sstuumdymaaurtyhoofrsthceonrcelsuuldtesodfthtahtethtewotesetxpmearteirmieanlts"isiscpornessiednetreeddimnutthaegteanbilce ibneltohwe. pprroecseednucreoesffSo9r-tmhiixs,a"sstahyi,s cisonafhoiugnhdliynqguebsytiteosntabmlateecroinacllupsriecoinp.itaDteivoina,tainodnsabfeorrrmatsitoannsdianrddose- nreosvpaolnisdecroenlcaltuisoinsohnispscafnorbteodxircaiwtynafnrdomputthaetmi.ve Imnuteaxgpeenriicmietnytr2e,ndweirthth$e9,redsoulstes lqeuveesltsioonfa3b7le5,aanndd m5a0t0erpiga/lmplrewceirpeitdatiesdcairndtehdeatsrbeeaitmnegn1t0m0etdoxiiucm,,buwtatsh(eihniagphpreorplreivaetleloyf)7i5n0clgu/demdl,inatthweheivcahlutahteiotenst of mutagenicity. rat nial sessmesReport Append va CO02RS Summary of Cytotoxic and Mutagenic Response of L5178Y Cells to N-EtFOSE Alcohol Concentration (ng/ml) Relative Cell Survival| (% Control) CE at Day 3 (%)| MutationFrequency x10 [SoheniComol 100 Tm Experiment 1, Without S9 [es | [ E [B e ffe o imes m ff f3r aysas]| Fosiive Control GS)[82 [79 [555 | Solve Conol [10 ExperimentT1,oWisth 9 Tra pfe so fm w e a] foFosoitve Conbol ONT)[01 r6 5f1 f e 7 i5 e8 ]| SolvenConol [100 Experiment 2, os Without S9 [75 | f fp s o o s Tf os e e w n a a ] Posive Conia (EVES) [8 OJ s es f[B SlovoewConmol TT m Ex1 perimenttm 2,f Wew0 imth S9 a 0 faaa rs 7 ] [ os yh w es f] aa] FPosive Conrol OVI)[10 [[ 3 sie] CONCLUSIONS Methodological problems prevent reaching definitive conclusions. Dr. Brian Myhr, Associate DirectorofGenetic and Cellular Toxicology at Covance Laboratories, Vienna, VA, has prepared a detailed nine-point critiqueofthis study, and concludes that the results are "not believable `without confirmation under better assay conditions." His criticisms include: Inadequate identification ofmouse lymphoma test strain; Useofexcessive, potentially toxic levels of S9 mix; Use of an inappropriate positive control chemical for the non-activation assay; LTeoerfmomSTi. evto,aCoveLabor oP. Licht, 3M, hy 1199 000226 Poor detection ofsmall colony mutants; Useofexcessively high concentrationsoftest chemical in mutation assays; Useofan excessively long mutant expression period (3 days); Useofinsufficiently large numbersofcells for mutation assays; and Over-interpretationofstudy results. REFERENCE NOTOX. 1998. Gene Mutation Evaluationofthe Test With LS187Y Mutagenic Activity Mouse Lymphoma ofT-6906 in an In Vitro Cells (With Independent Mammalian Repeat) Cell NOTOX Project 223458 ------ vas 000227 ROBUST SUMMARY- RS11 Title: MUTAGENICITY ASSAY, 1996 TEST ON T-6292 IN AN IN V10 MOUSE MICRONUCLEUS TEST SUBSTANCE Identity: T-6292, N-EFOSE alcohol Remarks: Amber waxy solid; purity not reported; Identification: T-6292 METHOD Method/guideline: No regulatory guideline Test type: micronucleus assay GLP: Yes Year study performed: 1996 Species/Strain: Mouse; Crl:CD-1 (ICR) BR Sex: Male and female No.of animals: 5/sex/dose Route of administration: Oral gavage in acetone:comn oil (40:60 v/v) emulsion. Doses/concentration levels: 550, 1100, and 2200 mg/kg Frequency of treatment: Single dose; subgroups examined after 24, 48, and 72 hours. hSteatteirsotgiecanleomuest)hpordosp:ortAinoanlsyosfiscoeflvlsarwiiathncmeicornonuunctlreain,sffoolrlmoewde(dobrryaDnukntnreatnts'fotersmteidf sifivganirfiiacnacnte. sRteudmya.rkAs:ranAgdeuflitndmiincges(taudgye (439/sdeaxy/sdoastet)iwmeeroefdcoosnidnugc)tewderweitqhuadroasnetsionfed10f0or0,7 1d4a0y0s,p1r8io0r0,to2200, saenldec2t6e0d0fomrgm/kagi,nasdtmuidnyibsatesreeddobnyhoyrpaolacgtaivvaigtey sineeanceattodnoes:ecsoomfo1il40su0smpegn/skiogn.or mDoorsee, laenvdelosne 1de0autph aotf2S2/0s0exmrge/ckegi.vinTghethmeahiinghstduodsyeulseveedlgwraosupusosefd St/osreexp/ldaocsee/phrairmvaersyt htiimgeh.-dAosseecaonnidmaarlys that pdioesdi.tivFeicvoenmtraolles(cayncdlofpivheosfpehmaamliedser,ec8e0ivmign/gkvge)hiwcelree(eaxcaetmoinnee:dcofmoromili,cr40o:n6u0c,le1i0amtl2/4kgh)ouarnsdafter sdotsuidnyg.forAslilgannsoimfaltosxiwceirtey.obFseemrovreadl ibmomneedimaatrerloywafwtaersdroescionvgeraendd apterthieoddiecsailglynattherdouhgahrvoeustttthieme aGnedimsspar.eaCdoodnesdlisdleisd,esfiwxeerdeinanmaeltyhzaendolf,oraPndCEst/aNinCeEd wraittiho Maandy-1G,r0u0n0wPaClEd pseolruatniionmaflolwleorweedscboyred for micronuclei. ref niAssam Report Appedic vas 000228 RESULTS `Toxicity: females at Significant bone all dose levels at marrow toxicity was the 72 hour harvest, evidenced by reduced and in positive control PCE/NCE females. ratio seen in `doGseen.otToxhiecpeofsfietcitvse: cNonetgraotlivperoduncoedintchreeaesxepeinctmeidcrsoignnuicfliecaatntedinpcorleyacsherionmamtiiccroenruyctlherioccyotmespaarteadny to vehicle females). control (3.36 + 0.97% v. 0.02 + 0.2% in males and 4.52 + 0.72% v. 0.14 + 0.06 in tRoeximcairtyk,sa:s eAvniidmeanlcsedinbayllhytproeaacttmievnittgyr(osuopmsereaclesiovwiintghNe-xEc(esFsOiSveEsaallciovhaotilosn)hoswhoerdtlsyiganfsteorfdosing. o`tThheerslorwe-mdaoisneedanhiympaolasctainved.soHmieghm-iddo-sdeoasneimmaallessdheavdelroepceodvedryesdpnbeya,20r.o4uhgohuhrasirafctoeartds,oshiunngc;hed p4o7s.t5urheo,urssquaifnttereddoesyiensg,.anOdncehmriomdo-ddaocsreyfoermrahleea,waasndalosnoefhoiugnhd-ddoesaedfaetm6a8l.e4whaosurfsoaufntderddeoasdinagt. CONCLUSIONS N-E(FOSE alcohol erythrocytes. was negative for inducing micronuclei in mouse bone marrow polychromatic REFERENCE Murli, H. 1996. Mutagenicity Test Coming Hazleton Inc., Vienna, VA on T-6292 in an Jn Vivo Mouse Micronucleus Assay. 22182. Final Report, May 2, 1996. CHV Study No. 17384- 0-455. Submitted to 3M, St Paul, Minnesota, 55144-1000. Dra ilsesResport Append V vas 000229 ROBUST SUMMARY- RS12 `Title: 1993 MUTAGENICITY TEST ON T-5710 IN AN IN VIVO RAT MICRONUCLEUS ASSAY, TEST SUBSTANCE Identity: T-5710, N-EIFOSE alcohol Remarks: (1-5710) Cream-colored granular material; purity not reported; Identification: L-10059 METHOD Method/guideline: FIFRA Guideline 84-2 Test type: In vivo rat micronucleus assay GLP: Yes Year study performed: 1993 Species/Strain: Charles River Sprague-Dawley rats. Sex: Male and female No. Animals: S/sex/dose Route of administration: Oral gavage in com oil suspension. Doses/concentration levels: 1250,2500, and 5000 625, 1250 mg/kg in com oil (10 ml/kg), Trial IT mg/kg in com oil (20 ml/kg), Trial I; 312.5, Frequency of treatment: Single dose; subgroups examined after 24, 48, and 72 hours. cSetlaltsiswtiitchalmimcertohnoudcsl:ei,AnfaollylsoiwseodfvbyarTiuaknecye'soSntsuqdueanrteizreodotraanrgeesitneset-rwiatnhsfaodrjmuesdtmpernoptforotrimounlstoifple comparisonsifsignificant. ARneimmaarlkss:werAedurlatndraotmsi(zaepdpraonxdimwaetieglhye8d wpreieokrstoolddo)siwnegr.eGqruoaurpasnotifne5d/sfeoxr/7dodsacy/shaprrvieosrtttoimsteuwdye.re cusoemdp,opulnusdatno abdediutsieodn,alif8n/eseedxed(T,riaaslr)epolrac1e0m/esnetxs(fTroiraalnIi)matlhsattrhaetcediiveeddptrhieorhitoghcedlolsheaorfvesttes.t Five pmoaslietsivaencdonftirvoelf(emcaylcelsoprheocsepihvaimngidvee,hi6c0lem(gc/okmg oiinl,st2e0rilmeUd/ekigoinnizTerdiawlaIt,er1,0 1m0Umklg/kign)TrwiearleIT) and p`eerxiaomdiinceadllayt t2h4rohuoguhrosuatfitehredsotsiundgy.foArlsligannsiomfatlosxiwceirtey.obMsearnvyedaniimmmaeldsiaitneTlryiaalftIedrideodsianngd aalnld baneaclyasmies,msooritbheuntrdiaplrwioarstaobtohreteedndaonfdtThreiasltIuldyw.asTcooondfuecwteadn.imTailbsiaslurbvoinveedmtaorprroowviwdaesarveacloivdered -------- var 00050 GatrtuhnewdaelsdigsnoaltuteidohnafrovelsltowteidmebyanGdeismpsraea.d Coondseldidessl,idfeisxewderien maentahlaynzoeld,faorndPCstEa/inNeCdEwirtahtiMoaayn-d 1,000 PCE per animal were scored for micronuclei. RESULTS `Toxicity: No significant bone marrow toxicity was seen, based on the PCE/NCE ratio dGoesneo.to`xThiecpeofsfietcitvse: cNonetgraotlivpero-d-uncoedintchreeaesxepeinctmeidcrsoingnuicfliecaatntedinpcorleyacsherionmamtiiccroenruyctlherioccyotmepsaarteadny 10 controls females). (4.64 0.64% v. 0.12 0.05% in males and 3.12 + 0.70% v. 0.12 0.04% in oRfemtoaxrikcist:y (TartiaaxliaI)wwaassabsoeretneadtdaullcdtooseexscaetssaibvoeutmo5rthaoluirtsyaafntdermdoorsiibnugn.diLtoy.w-IannTdrimaildI-I,doesveidence `groups recovered by and two males were ~23 hours; found dead high-dose animals at ~71 hours. remained ataxic through the endof the study CONCLUSIONS N-EWFOSE alcohol erythrocytes. was negative for inducing micronuclei in rat bone marrow polychromatic REFERENCE `MWuarslhii,nHg.ton1,99V3i.enMnuat,agVeAnic2i21t8y2T.estFionnalTR-e5p7o1r0t,inAparnilJn23V,iv1o99R3.at MHiWcrAonSutculdeyusNoA.ssa1y5.51H6a-z0l4e5t4o.n Dra idl ses Report Append var oceania ROBUST SUMMARY- RS13 `DTiNtlAe:SGYENNTOHTEOSXIISCAINTDY CTEELSLT PORNOTL-I57F1E0R.1ATIINOTNHAESISNAVYIVION/RIANTVILTIRVEORUCNESLCLHS,ED1U99L3ED TEST SUBSTANCE Identity: T-5710, N-E{FOSE alcohol Remarks: Cream-colored granular material; purity not reported; Identification: T-5710.1 METHOD Method/guideline: Williams 1980, Mirsalis et al. 1982; Butterworth 1987 "Test type: In Vivo/ln Vitro Unscheduled DNA synthesis and cell proliferation in rat liver cells. `Test System: Primary cells from animals dosed in vivo GLP: Yes Year study performed: 1993 Species/Strain/cell (CRL:CD BR). type/cell line: Primary hepatocytes from male Sprague-Dawley rat Metabolic activation: NA Statistical methods: For UDS assay: ProcedureofCasciano and Gaylor (1983). For cell ptrroalnisffeorramtaitoinoansosafy:daotnaew-awsaypearnfaolrysmiesdofivfavrariiaanncceesfwoellroewehdetbeyroDguennnoeuts)s.t-test (rank REMARKS Study Design: UDS Assay: G`mratoeuripasl.oAf3ddirattiso/ndaolseg/rtoiumpespoofitnthrreeceeirveecdeiavesdintghleevoerhailcgleavoargpeosdiotsievoefcoonnterolo.f tThirmeeepdooisnetssofwteerset2- 3obhtoauirnsedabndy p1e5r-f1u6sihoonurosfraaftterlidveorsiinngsiwthu ewnithhecpaaltcociyutmeasnwdermeaghnarevseistuemd.freHeeHpaatnokcsytbeaslawnecreed salts containing 0.5 mM cthyleneglycol-bis(B-aminoethy!ether)-N N-ietraacetic acid (EGTA) and (HWeMpeEs).bufCfeelrl,spwHer7e.2,cuflotlulroewdeidn bWy M50E-1w0i0thun1it0s%/mfleotfalcoblolvaigneensaesreuimn(WFiBlSl)iaimnscMuletdurieudmisEhes containing plastic coverslips. After incubation for2 hours at about 37C to allow attachment, utrniattiattaecdhtehdycmeildlsinweer(4e7rCeim/omvmeodlca)n.d cAufltteurrea mleabdeiliunmg rpeeprliaocdeod wf4ithhouWrsM, Ecelclosnwtearineirnegfe1d04wCiitfhml WME + 10% FBS containing 0.25 mM thymidine and incubated for 18-19 hours. Nuclei were then swollen by addition of 1% sodium citrate for 7-10 minutes, cells were fixed in acetic acid: LO -------- vas 000222 aetshsaensosled(1b:y3)c,oaunndtidnrgiendu.clFeiaxregdracionvserasnldipssuwbterraectpirnogctehseseadvefroargaeutnourmabdieorgroafgprhya.insUDinSnuwcalseus csoivzeerdsalriepa(so3 fcocvyetrospllipass/ma.niTmhale)nweet rneucmleeaasrugrreadinacnodunatvseroange5d0 froar ncdaocmhltyresaeltemcetnetdccoenldlistipoenr. Doses: 203, 405, 810 mg/kg Number of replicates: One Animals/dose: Three per timepoint (2 timepoints). Solvent: Com oil (10 ml/kg) Positive controls: Dimethylnitrosamine, 10 mg/kg. CfeorllpoPsriotliivfeercaotnitornolA)sswaeyr:eGdroosuepdsaosfffoirvteheyoUuDnSg maaslsaeya7du2lthoCurrls:bCefDoBrRe Ssapcarrifaigcue.e-ADtawalbeoyutratthse(4 ssuarmfeactei)mweit"htharneeAdlazyest p2rMiLorItoossamcortiificcep,u"mtphesleoaadneidmawlisthwe2rmeliomfplBarndtUedssoulubtciuotnan(e2o0umsgl/yml()do.rsa7l2 Hfioxuerdsinafnteeurtdroaslibnugf,felirveedr afonrdmaalicnr.ossP-asreacftifoinno-femdbuedoddeednsuemct(iloanbsel(i5ngumco)ntfrrool)m wtheerelerftelmaotevreald,arnidght dmeetdeicatne,d ainmdmurnioghhtisanttoecrhieomrilcoablelsyanwditfhrDomABdusotdaienn.umOnwceereappprreopparrieadt.e sCtealilnipnrgooliffedruatoidoennwuams sceocutnitoinnsgwoafslacboenlfeidrmceeldl,sawnadssptearinfionrgmwedasuscionngfitrhemeldeftaslastiemriallalroboen. aAltl tlheraeset 2li0v0er0lnoubcelseiexpaemrined, a`tanriamanldowmerbeyecxoammpiunteedr)fpreormseactmiionni.mumofthree sections, covering 8 microscope fields (selected RESULTS Genotoxic any dose. Effects: No increase in net nuclear grains or % cells with > 5 net nuclear grains at Cell Proliferation to controls. Effects: No increase in proportionof labeled liver cells at any dose compared Remarks: There were no test-specific confounding factors of nissn Reps Append va ceo223 In Vivo/In Vitro UDS and Liver Cell Proliferation in Rats Dosed with N-EXFOSE alcohol Mean Net Nuclear Grains | % Cells with = Net Nuclear Grains | Percent of Labeled Hepatocytes Control 0042037 0.73068 hod 267 0.73040 hid 0610.18 203wmhe sm Ris $10mke Positive Control (DMN 15 mg/kg) 0434040 733 0.630.41 73 0.05+054 72 20.10023 33 075020 733 0400.12 267 029%140 933 040048 13 -024+1.07 667 395236 igi 4053.38 38.00 5012262 an 0264026 TORT PT 315141586 CONCLUSIONS N-E(FOSE alcohol was negative for inducing Unscheduled DNA synthesis. REFERENCE CSiyfnotnhee,siMs.aAn.d C1e9l9l3.PrGoelniofetroaxtiicointAysTseasyt iOnnRaTt-5L7i1v0e.r1Ceilnltsh.eHIanzVlievtoo/nlnWaVsihtirnogUtnosnc,hVeideunlnead VDANA 22182. Final Report, September 14. HWA Corporation, St Paul, MN 55144-1000. Study No. 15516-0-494 Submitted to 3M DriassesReprs pedi var 0enz34 ROBUST SUMMARY - RS14 CTiOtlMe:POINUNVIDTSRTO-M22I4C7RCOoBCIAOLNODGTI-C2A24L8MCUoTC,AG1E97N8ICITY ASSAYS OF 3M COMPANY TEST SUBSTANCE pIedrefnltiutoyr:oocTt-a2n2e4su7lCfoonCa;teLi-n42w9a9t,era 50% by weight solutionof the diethanolammonium salt of pTy-r2i2d4i8niCuomCc;hl2o2r.id5e%soalfat orfeaanctiNo-nmeptrhoydlupcteorffleutohryolocatnadnmseutlhfyolnammeitdhoaectrhyalnaotels-baansded22gl.u5t%aorfylthe amide. Remarks: METHOD Method/Guideline Mayer, 1973 followed: Ames etal, 1975; Zimmermann and Schwaier, 1967; Brusick and `Test type: Reverse Mutation; Recombination Test system: Salmonella typhimurium; Saccharomyces cerevisiae GLP:N Year study performed: 1978 Species/Strainicell-type/cell line: TA100; Saccharomyees cerevisiae Salmonella D3 typhimurium TA1535, TA1537, TA1S38, TAOS, Metabolic activation: 0.5 ml of 10% S9 liver homogenate from Aroclor 1254 induced rats Cweo/npcleatnet,ra1t0i0o0nsugt/epsltaetde:, Plate 5000 pign/cpolraptoeration assay: 10 ug/plate, 50 pg/plate, 100 pg/plate, 500 DYeesassitcraetcoormmbeitnhaotdi:on0:.10.m1l%/,de0s.si5c%a,to1r.,00%.,55m.i0e%ssicator, 1.0 ml/dessicator, 5.0 ml/dessicator Yeast repeat assay at 1.0%, 2.0%, 4.0%, 5.0% Statistical methods used: None SR.ecmearrekviss:iaTehaesrseawyewreerneopseirgfnoifrimceadntwpirtohtobcootlhdcehveiamtiicoanlss. (a1n).d wTihtehpolanteepilnactoerppoerratteisotncaosnscaeyntraantdiotnh;e tohnelydesstsriacianstoTr Aas9s8ayawnadsTpAe1r0f0orfmoerdtwheitthesTt.-2H2o4w7evCeor,C guisvienngtthewocopmlpatleesxipteyrocfotnhceentdreastsiiocnatbourtaussseady and -- the li-- mitati-- ons i-- nvolv-- ed in setting it up, this is acceptable; (2) the positive controls we"re0c0ho0se2n 25 anictcroorfdliunogretnoe tahendstr2a-ianntahnrdamacitnievaftoironthceonpdliattieonisncaonrdpoirnactliuodnedasssoayd;iu1m,1a-ziddiec,hl9o-raomeitnhoyalcerneidifnore,th2e- dneesgiactciavteocronatsrsoalygwriotuhp Tf-or22al4l7asCsoayCs waansd w1a,te2r,.3,(43-)diTehpeoxpylbautteainnecofroprortahteioS.n acsesraeyviwsiitahe baostsahy.ageTnhtes adensdictchaetyoeraasstsaasy,sapylawtietshwTe-r2e24pr8ewpearreedraespefaotredt;hetshetadnedsaircdcaatsosraaysbsuaty nwoasterstunchoenmliycoanlcew.a(s4)adFdoerdtthoe the agar. The strains tested were S. typhimurium TA98 and TA 100. The test was performed both wshietlhfainndaw9i-tlhitoeurtdmeesticacbaotloirc. aActikvnaotiwonn.vPollautemsewoifthTo-u2t24li7dswwaesreadpdleadcetdosaidgelabsys sPiedreiindiashpetrhfaotrawtaesd p0.l5acmeld ainndth0e.1cemn1teorfotfeastncdheamtitcacahlewde1r0ethaeddbeodtttoomthoefdtehseicschaetlofr..ITnhdeecnreegaastiinvgeocrodnetrr,ol5.c0hemmii,ca1.l0wmals, water; the positive control chemical was 1,1-dichloroethylene. Both were treated in the same manner aats3T7-22C4.7.A Tmahgendeetsiicccstaitrorrerwwaisthsevaalneedsawnadsppllaacceeddoinn 2thmeabganseetoifceasctihrredrepsliactceationratrooeonsmurmeaiandetqauianteed: dispersion ofthe chemical. Plates were incubated for 8 hours, removed from the desiccators, their lids replaced and they were incubated at 37C counted. for an additional 42 hours before revertants were RESULTS Overall results: positive, negative, ambiguous: All tests were negative, Genotoxic effects (unconfirmed, dose-response, equi--vwitoh/cwitaholut activation): Negative both with and without activation. Cytotoxic concentration: T-2247 was not cytotoxic, In the other plate incorporation assay, T-2248 was toxic strains at 5000 ug/plate when tested without to strain TA1538 activation. It was at 1000 toxic at pg/plate and to all 1000 pg/plate to sTt-r2a2in48TAwLaSs3s7liaghntdlyatto5x0i0c0tougS./pclearteevfiosriaaellDo3thaetr5st%racionnscwehnternattieosntewdiwtihtohutmemteatbaobloilcicacatcitviavtaitoino.n. Statistical results: No statistical results were determined. Remarks: In the first assay with T-2248 and S. cerevisiae D3 without metabolic activation there. saseseamyewdatso rbeepesaotmeed satlig1h%t,i2nd%i,ca4t%i,onaonfdm5ut%agceonnicceinttyraattiothnes hwiigthhesatndcownictehnoturtataicotnivtaetsitoend., T5h%e.reThe wdiadsnnoot cianduisceatrieocnomobfianamtuitoangeinniSc.dcoesreevriesisapeonDs3e. aTnhdetrheewteersetinngoltaebsotr-sapteocriyficconccolnufdoeudndtihnatgTf-ac2t2o4r8s in any aspectofthe test. CONCLUSIONS TtyhpehtiemsutirnigumlaTboAr1a5t3or5y,cToAn1c0lu0d,eTdAtIhaSt3T7-,2T2A4I7Sa3n8d,Ta-n2d2T48A9w8erwehneonnmtuesttaegdeinnica pfloart.e incorporation assay with and without metabolic activation; that T2247 did not induce mutation in S. ref niasssmensReport Append va 000226 typhimurium TA98 and TA100 when tested neither chemical induced recombination in S. in a dessicator assay cerevisiae D3. for volatile chemical and that `These conclusions are accurate. REFERENCE CSiOmMmoPnA,NVY.F.CO19M78P.OIUNNVDISTRTO-2M2I47CRCoOCBIAONLDOGTI-2C2A4L8 MCoUCT.ASGREINIIntCerInTatYioAnaSl,SFAiYnaSl OReFpor3tM. Prepared for 3M Company, St. Paul, Minnesota 55101 OTHER None Dr ilAssssment Report Append vas ona? ROBUST SUMMARY - RS15 `MTiUtlTe:ATSIAOLNMOANSESLALYAW~IETSHCHPEFROIS,CH1I9A99COLIMAMMALIAN-MICROSOME REVERSE TEST SUBSTANCE Identity: PFOS; CAS #2795-39-3; FC-95; potassium perfluorooctylsulfonate, T-6295 Remarks: Lot 217; White crystalline powder; Stored at room temperature METHOD Method/Guideline 1983 followed: Ames ct al., 1975; Green and Muriel, 1976; Maron and Ames, Test type: Reverse mutation `Test system: Bacterial GLP: Y Year study performed: 1999 Species/Strain/cell-type/cell line: Salmonella typhimurium TA1535, TA100, TA9S, TA1S37 Escherichia coli WP2urA Metabolic rats activation: 0.1 ml 89 liver homogenate from Aroclor 1254 induced Sprague-Dawley Cngopnlcaetnet,ra3t,i3o30nsigt/epsltaetde:,Sa.ntdyp5h,i0m0u0rgi/upml:at3e3.u3g/ppgl/aptleatwei,th10a0ctpigv/aptliaotnea,n3d330.p3g3/3plpagtpel,a1t,e0,001.00 nHgg//ppllaattee,a3n.d335,u0g0/p0lautge/,pl1a0t.e0wuigt/hpoluattea,ct3i3v.a3tipong./plate plate, 100 pg/plate, 3333 pg/plate, 1,000 E. coli: 33.3 ug/plate, ng/plate both with and 100 ug/plate, 3333 without activation. pg/plate, 1,000 pg/plate, 3,330 pg/plate, and 5,000 Statistical methods used: None Rcoenmcaenrtkrsa:tiTohnearnedwceornetrnolo;stihgenipfoisciatnitvpercootnotcroollsdewveirateiosntrsa.in(1)aTnhdearcteivwaetrioen3coplnadtietsiopnerspteecstific and niintcrlouqdueidnobleinnzeo-[Na-]opxyirdeen.e,Th2e-nviterhoifcllueorceonnet,ro2l-wamaisnoDaMnSthOr;ace(2n)e,thseosdoiluvemnatziwdaes, DICMRS-O19;1(a3)ndth4e- aasnsdayWPw2ausvnroAt,retpheearteehd.ad(4t)oFboeratthleetaessattar2t-ifcolledtionbcerecaosnesiindetrheedmpeoasnitirveeveirntasnttrsaipnesrTpAl9at8e,oTveAr1t0h0at ofthe appropriate vehicle control. The increase had to be accompanied by a dose response to Dra itlsesRepsort Append V vas COOnC8 ain3c-rfeoalsdinignccroenacseentirnatthieonmseoafnthreevteersttanatrtsicpleer. pFloartesotrvaeirnsthTaAto1fSt3h5eaanpdprToAprIiSa3te7vtehheircelheacdonbteroalt. lTehaset increase article. had to be accompanied by a dose response to increasing concentrationsof the test RESULTS Overall results: positive, negative, ambiguous: Negative Genotoxic effects `was not genotoxic (wuhnecnontefsitremdeedi,thdeorswei-trhesoprownisteh,ouetqumievtoacbaolli--cwaicttihv/awtiiotnh.out activation): PFOS `CThyitsotcoyxtiotcoxciocnicteyntwraastieovni:deCnycteodtboxyicaitsyliwghatsrneodtuectdiaotn5i0n0t0heugb/apclteartiealwiltahwon.ut metabolic activation. Statistical results: Results were not evaluated statistically. tRheemraarnkgse:ofTthheerevewheircelencoonttersotl-ss.pecific confounding factors. Mutation frequencies were within CONCLUSIONS Author's conclusions are that PFOS is negative in this assay. This is accurate. REFERENCE AMsecscahyiw,iMt.hSP.FO19S9.9.CoSvalamnocneelLlabao-raEtsocrhieersiIcnhci.a(CCoolvian/cMea)mmVaileinnaan,-MViircgrionsioam2e2R1e8v2eFrisnealMuRteaptoirotn Covance Study 55144-1000 No.: 20784-0409. Submitted to: 3M Corporate Toxicology St. Paul, Minnesota OTHER None [Lp -- ---- te ------ec vas 000229 ROBUST SUMMARY - RS16 `Title: SALMONELLA TYPHIMURIUM SPOT TEST ON FC-95, 1977 TEST SUBSTANCE Identity: FC-95 (CAS #2795-39-3; potassium perfluorooctylsulfonate, T-6295, PFOS) Remarks: METHOD Method/Guideline followed: Spot test Test type: Reverse mutation Test system: Bacterial GLP:N Year study performed: 1977 Species/Strain/cell-type/cell line: Salmonella typhimurium TA1535, TASS, TA100 Metabolic activation: Aroclor 1254 rat liver $-9 Concentrations tested: 10 meg Statistical methods used: None. cReenmtaerrkofs:plaPtaepsoefrSd.isctsypsahtiumruarteidumwictihthtehreweiqtuhivoralweintthoofut10ramt eligveorfSF-9C.-9T5hewesorlevepnltacweadsinDtMhSeO. `Twhaes ppoossiittiivvee cinontthriosltewsta.sN2o-armeipneoaftlsuwoerreenepeartf1o0rmmede.g aAndpo1simteigv.e r2e-spAoFnsreeqiusijreusdgaectdivbaytitohne and formationof a ringofmutant colonies around the disc with the test agent RESULTS Overall results: positive, negative, ambiguous: Cannot bejudged. UGnecnoontfoixrimceedffbeecctsau(suenocfotnefsitramnedd,redpoosret-irnegscpoonndsiet,ioenqsu.ivocal -- with/without activation): Cagyetnottodxififcusceosncienntotrtahteiaogna:rCfornocmentthreatdiisocnsancdancnaontnobte judged from the be quantitated. spot test because the test Statistical results: None [-------- -- var oenzio aRequmaalritkast:iveThiendsipcoattotresotfimsurteaggaerndiecditays,hniegghaltyiviensreenssuilttisvemuasntdbwehicloenfpiosrimteidveinreasuplltastemay serve as incorporation assay. CONCLUSIONS iTnhfiosrimsaatioonnep-rpeasgeentmeedmtooerveaplourat.teInthaeddreistuilotns.to being an insensitive assay, there is insufficient REFERENCE LRaobholrfaitnogr,iSe.sR.Inc1.97I7n.teSroaflfmicoenCeolrlryeMsapmomnadleincaen-tMo iAc.rNo.sWoemleteMru,taEgnevniircointmyenTtesatlinEgn.gi3nMcerRiinkger& Control. OTHER None Lr ---- vas oon2a1 ROBUST SUMMARY - RS17 Title: BACTERIAL REVERSE MUTATION TEST OF 9-1, 1996 TEST SUBSTANCE I(dCe=n0t-i2t)y:ey5c-l1o;heRxeyalcstuilofnopnryo!dfulcutoorfidpe,erpfoltuaosrsoiduimmectahrybloyncaltoeheaxnydlssuullffuorniyc]acfildu;orCidAe,Sp#er6f7l5u8o4r-o4a2lk-y3l [the main component A(n=2)] Remarks: Lot 293, White powder, MW ~500, 100% wiw% pure, Stored at room temperature METHOD Method/Guideline September 1, 1988 followed: Standards for Toxicity Investigations (Japan's MOL, No. 77, Test type: Reverse mutation Test system: Bacterial GLP: Y Year study performed: 1996 Species/Strain'cell-type/cell TAIS37 line: Salmonella typhimurium TA100, TA98, TALS35 and Escherichia coli WP2uwrA Metabolic activation: 5.6-benzoflavone S9 homogenate from male SD male rats pretreated with phenobarbital and Concentrations tested: For S. typhimurium TA100, TA1S35, TAIS37 and E. coli WP2urA. wngi/tphloautte.activation: 39.1 ug/plate, 78.1ug/plate, 156pg/plate, 313 pg/plate, 625pg/plate, and1250 For S. typhimurium TA98 without activation and for all strains with activation56] g/plate, 315 uglplate, 625 pg/plate, 1250 pg/plate, 2500 pg/plate, and S000 pg/plate. Statistical methods used: None cRoenmtraorlkwsa:sTtheesrteedwienrdeupnloicsaitgen;iftihceanntepgraottiovceoclodnetvrioaltiwoanss.te(s1t)edEaicnhtrtiepslticcaotnec;e(n2t)rathteiosnolavnedntpoasnidtive nacetgiavtaitvieoncosnytsrtoelmwaansdDiMncSlOud;ed(:3)2t-hAeF;possoitdiivuemcoanztirdoel,sIwCeRr-e19c1h,osaennd a2c-caomridnionagntthorsatcreainne;an(d4) the tceosltowniaessnwoatsrtewpeiacteedo;r m(5o)rTehtehetensetgsautbisvteacnocnetrwoals, jthuedrgeewdatso apodsoisteiv-erewshpeonnstehreenlatiuonsmhoipfbraenvdeertthraent orefsulntsiawesrerreeproRdepuocritblAep.penis vay conzaz RESULTS Overall results: positive, negative, ambiguous: Negative NGeegnaottiovxeiwcietfhfeacntds (wiutnhcoountfiarctmievda,tidoonse-response, equivocal -- with/without activation): CcoyltioWtoPx2icucvornAceanntdra5t0i0o0n:pg1/0pl0a0teugw/iptlhatSc. itnySp.htiympuhriimuumrTiAum98TAw1i0t0ho,uTtAaLctSi3vaSt,ioTn.A15S03070,uagn/dplEa.te with S. typhimurium TA100, TAIS35, TA1537, and E. coli WP2 uvrA with activation. Statistical results: Statistics were not used to evaluate the results. tReestmeadr.kTsh:eTphoesirteivweacsonntoroilnscrgeaavsee tinhetheexpneucmtbederroefsproenvsee.rtaNnetgsawtiitvhe aconnytrsotlrasiwnearteanwyitchoinncetnhteration historical range for the assay. CONCLUSIONS The authors conclude that the test substance is negative in this assay. This is correct, REFERENCE OBiAtaCT87E7RJIaApaLn,REFiVnaElRRSepEorMt.UTFoArTSIuOmNitToEmoST3MOFLi9m-i1.ted1,99K6a.nHaigtaawRae,s2ea2r9cJhaLpaabnoratories, Hita, OTHER Nothing rat ilAssent Ror Append Vso 000293 ROBUST SUMMARY - RS18 Title: MUTAGENICITY EVALUATION OF T-2014 CoC IN THE AMES SALMONELLA/MICROSOME PLATE TEST, 1978 TEST SUBSTANCE Identity: T-2014 CoC, CAS #2795-39-3, potassium perfluorooctylsulfonate FC-95, PFOS Remarks: White Powder METHOD Method/Guideline followed: Ames, 1975 Test type: Reverse mutation Test system: Bacteria; Yeast GLP: N Year study performed: 1977/1978 Species/Strain/cell-type/cell line: Salmonella typhimurium TA100, TA1535, TAIS37, TAIS38, `TA09, Saccharomyces cerevisiae D4 Metabolic activation: 0.1 + 05 ml S9 homogenateofAroclor 1254 induced Sprague Dawley rat liver Concentrations tested: 0.1ug/plate, 1.0 pg/plate, 10.0 pg/plate, 100 pg/plate, 500 pg/plate nonactivated; 0.1 ugplate, 1.0 pg/plate, 10.0 ug/plate, 100 pg/plate, 500 pg/plate activated Statistical methods used: None Remarks: There were no significant protocol variations. (1) For the time when the test was done (1977) a single plate per concentration was routine. (2) the negative control was the solvent DMSO; the positive controls were chosen according to strain being tested and activation condition and included ethyl methanesulfonate, quinacrine mustard, nitroflourene, 2-anthramine; and dimethylnitrosamine. (3) a limited repeat study was done with strain TA100 both with and without activation because the testing laboratory believed that there was some evidenceofmutagenicity with this strain. The doses tested without activation were 100 pg/plate, 500 ug/plate, and 1000 ug/plate and 500 ug/plate, 1000 pg/platc, and 2000 wg/plate with activation. However,a reviewof the data shows that was originally thought to be mutagenicity was within the normal variationof the assay. `The repeat was inadequate because the doses tested were too high and to toxic to shed any light on possible mutagenic activity; there were no signs ofmutagenicity in anyofthe other strains tested. "The test with Saccharomyces was also negative. (4) criteria to evaluate results were as follows: dose- rat nial sess Report Appi vai oeo244 response over 3 concentrations with lowest increase equal to 3X the solvent control for TALS3S, TAI537 and TALS38. Dose-response over 3 concentrations with lowest increase equal to 3X background for TA100 and 2x-3X background for TA98 and D4. RESULTS Overall results: positive, negative, ambiguous: Negative Genotoxic effects (unconfirmed, dose-response, equivocal -- with/without activation): Negative with and without activation Cytotoxic concentration: 1000 ug/ml both with and without activation. Statistical results: No statistics performed. Remarks: None CONCLUSIONS Author's conclusions are accurate but for wrong reasons. The test chemical is negative not because it was negative on repeat testing but because what was taken as mutagenicity in the first test was within normal variationofthe assay. REFERENCE Litton Bionetics, Inc. Kensington, Maryland 20795 1978. Mutagenicity Evaluation of T-2014 CoC in the Ames Salmonella/Microsome Plate Test. Final Report. Submitted to: 3M Company, Saint Paul, Minnesota 55101 OTHER None raf niaAssos Report Appecic v2 000295 ROBUST SUMMARY - RS19 `Title: MUTAGENICITY TEST ON T-6295 IN AN IN VIVO MOUSE MICRONUCLEUS ASSAY, 1996 TEST SUBSTANCE Identity: T-6295, CAS #2795-39-3, potassium perfluorooctylsulfonate, FC-95, PFOS Remarks: Off-white mixture of powder and flakes METHOD Method/Guideline followed: Heddle, 1983 Test type: Micronucleus GLP: Y Year study performed: 1996 Species/Strain: Mouse; Crl:CD-1(ICR)BR Sex: Males & Females No. animals/sex/dose: 5/sex/dose Vehicle (if used): Deionized water Route of administration: Oral Doses: 237.5 mg/kg, 450 mg/kg, 950 mg/kg, Frequency of treatment: Single dose Statistical methods used: Analysis of variance; Dunnet's t-test Remarks: There were no significant protocol deviations. (1) Animals were 9 weeks and 1 day old at startofdosing males; weight range for the males was 29.9 ~37.0 g; for females it was 23.129.2 g; (2) the vehicle was deionized water; (3) the test lasted 72 hours; (4) the test material was a(6d)mitnhiesvteehriecdleascoantsrionlglweaosralH,d0o;set;he(5p)oasliltitvreeactomnetnrtolgwroausps80wemrge/ksgamcpylceldopatho2s4,ph4a8miadned d7i2sshooluvresd; in water and administered by gavage. Controls were sampled at 24 hours only. Control groups consisted of5 males and 5 females cach. (7) No clinical examinations were made. (8) No necropsics or other gross examinations were made on these animals. (9) Micronuclei were evaluated in the bone marrowoftreated animals. Frequency of PCE vs. NCEs was determined Dbry sncoirinAgstsheenntuRmepboretropfePiCEV and NCES in the optic fields while scoring the first 100v0r onN296 erythrocytes. A positive was judged by an increase in micronucleated polychromatic erythrocytes. over levels observed in the vehicle controls in either sex or at any harvest time. Bone marrow toxicity was judged by a significant reduction in PCE/NCE ratios in cither sex at any harvest time. (10) The M.T.D. was chosen on the basis o2f preliminary dose sclection assays both of `which showed significant toxicity at the highest dose tested. RESULTS Effect on mitotic index or PCE/NCE ratio by dose level and sex: PCE:NCE Ratio 237.5 mg/kg 24 hours: males 0.57 + 0.11; females 0.52 + 0.10 48 hours: males 0.48 + 0.04; females 0.80 0.10 72 hours: males 0.39 + 0.11; females 0.42 + 0.14 450 mg/kg 24 hours: males 0.75 + 0.11; females0.59 + 0.08 48 hours: males 0.71 + 0.05; females 0.37 + 0.07 72 hours: males0.29 + 0.06; females 0.40 = 0.12 950 mg/kg 24 hours: males 0.56 + 0.13; females 0.59 + 0.08 48 hours: males 0.54 + 0.08; females 0.44 + 0.11 72 hours: males 0.17 + 0.05; females 0.17 0.05 Genotoxic effects (unconfirmed, dose-response, equivocal): Negative Statistical results: `The PCE:NCE ratio was reduced in 237.5 mg/kg males at 48 and 72 hours; in 450 mg/kg males at 72 hours and in 450 mg/kg females at 48 hours and in 950 mg/kg males at 48 and 72 hours and in 950 mg/kg females at 72 hours. There was no statistically significant increase in the number of micronucleated PCE over the controls in any treatment group. The positive control induced a significant increase in the number of mPCE in both males and females and reduced the PCE:NCE ratio in females only at 24 hours. Remarks: (1) Animals were examined approximately 1-2 hours before sampling for signsof toxicity and `mortality. Animals in the 237.5 mg/kg group remained healthy throughout the treatmentperiod. (2) Both males and females in the 950 mg/kg dose group began dying about 22 hours after treatment. Also at 22 hours 2 males in the 950 mg/kg dose group went into convulsions when their cage was opened but recovered in a few minutes. At about 46 hours after treatment 1 female from the 450 mg/kg dose group and more males and females from the 950 mg/kg dose group were found dead and at about 71 hours after treatment, one male from the 950 mg/kg dose group was found dead. All surviving animals appeared normal at that point. (3) No other clinical signs were noted or reported. (4) Body weight changes were not reported. (5) Food and water OttdosntsmnSpnur pec vaycoozay consumption were not reported. (6) There was no increase in the percentofmicronucleated PCEs at any dose level tested or at any time period sampled. CONCLUSIONS: The author concludes that PFOS is negative in the mouse bonemarrow micronucleus assay. This is an accurate assessment. REFERENCE: Murli, H. 1996. Mutagenicity Test on T-6295 in an In Vivo Mouse Micronucleus Assay. Coming Hazelton Inc. (CHV), Vienna, Virginia 22182. Final Report. Submitted to 3M St. Paul, Minnesota 55144-1000 CHV Study No.: 17403-0-455. OTHER: None ------ vas 0N02eg ROBUST SUMMARY - RS20 Title: Unscheduled DNA Synthesis in Rat Liver Primary Cell Cultures with PFOS, 1999 TEST SUBSTANCE Identity: PFOS; CAS #2795-39-3; potassium perfluorooctylsulfonate; T-6295 Remarks: Lot 217, White crystalline powder; Stored at ambient temperature METHOD Method/Guideline followed: Williams, 1977; Williams, 1980; Butterworth et al., 1987 Test type: Unscheduled DNA Synthesis in Mammalian Cells in Culture `Test system: Primary cells in culture: GLP: Y Year study performed: 1999 Species/Strain/cell-type/cell line: Primary hepatocytes from a Fischer 344 rat male rat. Metabolic activation: None C1.o0ncpegn/tmlr,at2i.o5nusg/temslt,edS:p1g5/mclo,nc1e0n.t0raptgi/omnls abnedtw2e5e.n00p./02m5,igc/homsleanndfor40e0va0luga/tmilon.bSaisx,ed0.u5popgn/ml, cytotoxicity. Statistical methods used: None Rweermeariknscu:baTtheedrefowre1r9e.6n-o20s.i0gnhiofiucsa,nttphreonttohceolasdseaviyatwiaosns.ter(m1)inTartiepdliacnatde'cHu-ltthuyremsidoinnecoavderdseldiptso the cmuolutnurteesdfoonr 3sl0idmeisn,udtiepspaefdteirnwehmiuclhsitohne acenldlsstwoerreed ffioxred6,ddaryisedatov2-e8rnCighatf,tecrowvehrisclhiptsheweermeulsions mweeraendneevtelnuocpleeda,r fgirxaeidn acnodunsttadienetde.rm1i5n0edc.el(l2s)pTehredossoelvweentreforreatdhe(a5s0sfayrowmacsaDchMcSoOve;rs(l3i)p)thaenred wtahes no follow-up repeat considered positive, study; (4) the there must be positive control was 2-AAF; (5) for an increase in the mean net nuclear a treatment grain count to to be at least 5 ogrfaniuncslpeierwintuhclfeiuvse aorbomvoertehenectongrcauirnrsenstucvhehtihcaltetchoenptreorlcevnatlaugee,oafntdh/eosreannuicnlcerieaisneteisnttchueltnuurmesbeisr 10% above the percentage of these criteria. seen in the vehicle control cultures. The positive control satisfied both RESULTS Or itssmeRneposrt ppedic vss cooze9 Overall results: positive, negative, ambiguous: Negative Genotoxic Negative effects (unconfirmed, dose-response, equi--vwitoh/cwitaholut activation): C25y.t0otpogx/imlc.coCnecllenmtorratpihoonl:ogEyxcweasssisvueitcaybtloetofxoircaintaylaytsiasnadtaabnodvebe5l0o.w0 2u5g./0mlg;/wme.ak cytotoxicity at Statistical results: The results were not evaluated statistically. Remarks: There were no test-specific confounding factors CONCLUSIONS The author concludes that PFOS is negative in this assay. This is accurate. REFERENCE CCiofvoannecMe.LAa.bor1a99t9o.riUesnsIcnch.edVuileendnaD,NVAAS2y2n1t8he2sFiisnainl RRaetpoLritv.eCroPvrainmcaerySCteuldlyCNuol.t:ur2e0s78w0it-h04P4F7O.S. `Submitted to 3M Corporate Toxicology St. Paul, MN 55144-1000 OTHER None -------- var 0Co250 ROBUST SUMMARY - RS21 Title: CHROMOSOMAL ABERRATIONS IN HUMAN WHOLE BLOOD LYMPHOCYTES WITH PFOS, 1999 TEST SUBSTANCE Identity: PFOS; FC-95; CAS #2795-39-3; potassium perfluorooctylsulfonate; T-6295 Remarks: Lot #217, White crystalline powder, stored at room temperature METHOD Method/Guideline followed: Galloway, 1994 Test type: In vitro cytogenetics Test system: Human cells in culture GLP: Y Year study performed: 1999 `Species/Strain/cell-type/cell line: Human lymphocytes Metabolic activation: Aroclor 1254 induced rat liver S9 homogenate, 15.0 uL/ml, plus NADP and isocitric acid. Concentrations tested: 12.5 pg/ml, 24.9 pg/ml, 49.7 pg/ml, 99.3 ug/ml, 149 ug/ml, 199 pg/ml, 249 pg/ml, 299 pg/ml, 349 ug/ml, 449 pg/ml, 599 pg/ml without activation. 12.5 pg/ml, 24.9 pg/ml, 49.7 pg/ml, 99.3 ug/ml, 149 pg/ml, 199 pg/ml, 249 pg/ml, 349 ug/ml, 449 pg/ml with activation Statistical methods used: Cochran-Armitage test for linear trend; Fisher's Exact Test Remarks: There were no significant protocol deviations. (1) Each concentration was tested in replicate; each replicate was considered an independent unit. The negative control for the nonactivation assay was DMSO at 10 pl/ml, which was the highest concentration used in the test cultures; in the activation assay it was DMSO plus the S9 mix; the positive control was mitomycin C for the nonactivation assay and cyclophosphamide for the activation assay. Three `concentrationsof each positive control were tested. Cultures were exposed to chemical for 3 hours and harvested 22 hours later. One hundred metaphases from cach replicateofthe useable treatment cultures and the solvent and one dose ofthe positive control were used; mitotic index was evaluated by analysing the numberofmitotic cells in at least 1000 cells per culture; (2) the solvent for the chemical was DMSO; (3) there was no follow up study done although in a study such as this where there are negative results after 3 hours incubation with a 22 hour harvest time Dr AsmA et Append ovha ozE1 a second study with a continuous exposureof 22 hours for the nonactivated portionofthe assay siisgrneifciocmamntenidncerde.as(e4)(pT<h0e.0t1e)stinartthieclne wuoumldobfhaceveelrlbseweintchocnhsirdoemroesdopmoaslitaibveeirrfataitohnesreathoandeboerenmoare ocobnsceernvteradtiinontsh.e nThuembteesrtoafrcteicllleswwaisthcocnhsriodmeoresdomnaeglaatbievrerabteicoanusseattahneryecwoancsenntorastiignoinfitceastnetdi.ncrease RESULTS Overall results: positive, negative, ambiguous: Negative NGeegnaottiovxeicboetfhfewcittsh(aunndcowniftihromuteda,ctdivoastei-onr.esponse, equivocal -- with/without activation): aCcyttiovtaotxioincwceornecetnhterafitristonc:yto2t9o9xipcgc/omnlcewnittrhaotuitonmsettaesbtoeldicasaectviivdaetnicoendanbdy a19r9eduugc/tmilonwiinthmitotic index. Statistical results: Negative cRuelmtuarreksst:reMaitetdotwiicthin1d2e.x5wuags/mrle,du2c4e.d9 u3g8/%m,l,84%9.175%p,g/1m5l%,,991.23%u,g/1m9l%,,12449%,ug6/m9l%, 2an4d9 9ug2/%mli,n 299 pg/ml, 149 cultures treated pg/ml and 199 ig/ml, 449 249 ug/ml pg/ml, without activation. Aberrations 299 pg/ml, and 349 pg/ml, were analysed from t`rWeiatthemdewtiatbhol4i9c.7acutgi/vamtli,on1,99mituogt/imcl,in2d4e9x gw/amslr,edauncded29b9yu1g2/m%l,. 4A1b%e,rr7a1t%io,nsanwder5e3%anailnycsueldtufrreosm `cumlettuarpehsasterseawteedrewiatvhai9l9a.b3legf/omrla,na1ly4s9ispgf/rmolm, c1u9l9tuprge/smtlr,eaatnedd w2i9t9hu2g9/9mlg./Omnl,ly 27 and 4 CONCLUSIONS: lymphocytes; this Author's conclusions is correct as stated. are that PFOS does ot cause mutation in human REFERENCE: Murli, H. Lymphocytes with PFOS. 1999. Chromosomal Aberrations in Human Covance Laboratories Inc. (Covance) Final Whole Blood Report. Covance Study No.: 20784-0-449. Submitted to: 3M Corporate Toxicology, St. Paul Minnesota 55144-1000. OTHER: None -------- vs 000252 ROBUST SUMMARY - RS22 T(iwtilteh:inEdveapleuantdieonntorfeptehaet)m,u1t9a9g4e.nic activity of T-5874 in the Ames Salmonella/microsome test TEST SUBSTANCE Identity: N-Methy! perfluorooctanesulfonamido ethanol (N-McFOSE) Remarks: Cream solid; Identification T-5874, batch 2334, purity "100%" METHOD Method/guideline: OECD Guideline No. 471 Test type: Salmonella- mammalian microsome reverse mutation assay GLP: Yes (OECD) Year: 1994 Species/Strains Salmonella typhimuriumTA-1535, TA-1537, TA-98, TA-100. Metabolic activation: $9 from Aroclor-induced rat liver. Statistical methods: None REMARKS Study Design: Concentration (with and without $9): 100, 333, 1000, 3330, 5000 pg/plate with all strains, plus 3,10,33 ugplatefor TAL00. Number of replicates: Two Plates/test: Three per dose. Pmorlotceenduargea:r sAulpipqlueomtesnotfed10w0ituhlobfiocteilnlsaonfd aeatcrhacsetorfaihnisftriodminoeve(fronrigShatlmcounletulrleas)woerrweitmhixed with tturbyep,toapnhdanpo(ufroredE.ovCoelri)t.he Asunrfaapcperoofprsiealteectqiuvaentaigtayropflatteesst.maFtoerriaaclti(vinatDioMnSaOss)ayws,as0.a5dmdledoftoSe9ach mix was addedbeforemixing and pouring. Salmonella plates were incubated for 48 hours at 37C and scored for numbersofrevertants. Yeast D4 plates were incubated at 30C (nonactivation) or 37C (with $9) for 3-5 days and scored for convertants. Solvent: DMSO (100 plate) Positive controls: Nonactivation: Sodium azide, | pg/plate for TA-1535; rat nilsessment Report Append ven 000253 methylmethanesulfonate, 650 ug/plate for TA-100; 9-aminoacridine, 60 pg/plate for TA-1537; daunomycine TA-1537, and 4 pg/platc for TA-98. Activation: 2-aminoanthracene, 0.5 g/plate for TA-98 and TA-100. $ g/plate for TA-1535, RESULTS pCryetcoitpoitxaitciocnoonfcteensttramtaitoenri:alNaot ttowxoichiitgyhsesetendowsicts.h or without S9 in TA100 at any dose. Some Genotoxic effects: No metabolic activation. increase in mutants seen at any dose, with any strain, with or without REMARKS `Some precipitationoftest material at two highest doses. CONCLUSIONS N-MeFOSE was not mutagenic in the Ames assay. REFERENCE NSaOlTmoOnXell1a9/9m4i.crEovsaolmueattiesotno(wfitthheimnduetpaegnedneinctarcetpievaitt)y.ofNTO-T58O7X4 iPnrotjheectAm1e15s932; NOTOX Substance 38187 Dr iAsseRnpotr-Append V val . 000254 ROBUST SUMMARY - R23 Title: Evaluationof the ability of T-5874 to induce chromosome aberrations in cultured peripheral human lymphocytes (with independent repeat)., 1994 TEST SUBSTANCE Identity: N-Methy! perfluorooctanesulfonamido ethanol (N-McFOSE) Remarks: Cream solid; Identification T-5874, batch 2334, purity "100%" METHOD Method/guideline: OECD Guideline No. 473 Test type: Chromosomal aberrations in human whole blood lymphocytes GLP: Yes (OECD) Year: 1999 Species/Strain: Venous blood from healthy adult male humans. Metabolic activation: S9 from Aroclor-induced rat liver (method ofAmes et al. 1975). Statistical methods: Chi-square test REMARKS FIELD FOR TEST CONDITIONS Study Design: wWehroeleinbcluoboadtecdulftourr2esdianysF1p0ricourlttouraeddmietdiionumo,f tseustppmlaetemreinatlewdiwtihthS99mmigx/mflorp3hhyotuorhse,maogrewliutthionuitn 89 for 24 or 48 hours. Fresh medium was added and the cells incubated with S9 for an additional 20-22 or 44-46 hours, with 0.5 ug/ml Colcemid added during the last three hours prior (t3o:h1)a.rveSslti.deCsewlelsreweprreepcaernetdr,ifaiurgeddr,ietdr,eaatnedd swtiatihnehdypwoittohni5c%KGCiIemasnda fsioxleudtiionnmfeotrhaannaolly:siasceotfic acid mitotic index and chromosome aberrations. A pilot study with concentrationsof3, 10, 33, 100, `and 333 ug/ml was used 10 set the concentrations for the aberration test Concentration: -S9: 10, 33, 56, 100, 178, & 333 pg/ml (24hr exposure); 33, 100, 178, & 333 ng/ml (48 exposure) hour used exposure); for scoring Only 56, 100 chromosome and 178 g/ml aberrations. (24 hr exposure) and 178 ig/ml (48 hour +89: 10,33, 100, & 333 ug/ml (24 hr & 48 hr exposure); 33, 100, and 333 pg/ml (24 hr exposure) and 100 & 333 g/ml (48 hour exposure) used for scoring chromosome aberrations. (Repeat trial used doses for 24-hour exposure only, and scored slides at 33, 100, & 178 pg/ml 59,and 33, 100, & 333 pg/ml +59. ------ va 0002TS Number of replicates: Two Cultures/test: Two. Solvent: DMSO (0.9%) Positive controls: Nonactivation: Mitomycin C, 0.2 ug/ml in HBSS for 24-hour treatment; ,0.1 ng/ml in HBSS for 48-hour treatment. Activation: cyclophosphamide, 15 jig/ml in HBSS. RESULTS Cytotoxic concentration: Some reduction in mitotic index compared to control seen at 178 and 333 pg/ml Genotoxic activation. effects: No increase in chromosome aberrations with or without metabolic REMARKS CONCLUSIONS N-McFOSE was negative for inducing chromosome aberrations. REFERENCE cNuOltTurOedXpe1r9i9p4h.erEavlalhuuamtaionnolfymtphheocabyitleisty(owfitTh-5i8nd7e4pteondienndtucreepecaht)r.omNosOoTmOeXabePrrroajteicotn1s1i5n919; NOTOX Substance 38187 -------- vas 000256 ROBUST SUMMARY - R24 TMiuttlaet:ioEnvaTleusattiWointohftLh5e18M7uYtaMgoenuisceALcytimvpithyoomfaT-Ce5l8l7s4(iWnitahn IInndVeipternodMeantmmReapleiaat)n,C1al9l94Gene TEST SUBSTANCE Identity: N-Methyl perfluorooctanesulfonamido ethanol (N-McFOSE) Remarks: Cream solid; purity "97%"; Identification: T-5874 batch 2334, METHOD Method/guideline: L133 & [248 OECD Guideline 476; EEC Directive 67/S48/EEC, EEC Publication No. Test type: Reverse mutation assay Test System: Mammalian cel line GLP: Yes (OECD). Year study performed: 1994 Species/Strain: LS187Y mouse lymphoma cells. Metabolic activation: S9 from Aroclor-induced adult male Wistar ratliveradded at 20% v/v. Statistical methods: None Remarks: Study Design: CEoxnpceernitmreantti1on&: 2R:an1g0e,f3i3nd1i0n0gatnesdt:331,33p.3g,/m1l0,w3i3t,h 1a0n0d, waintdho3u3t3Sp9g./ml with and without $9; Number of replicates: 2 Plates/test: Three P90 plates/concentration plates/concentration for mutation frequency for cloning efficiency (~150000 cells/plate). (200 cells/plate); ten P90 Solvent: Dimethylsulfoxide (final concentration in culture medium, 0.8%). Pwoistihtoiuvteccaolnctiruomlsa:ndWimtahgonuets$i9u:m)e;thwyiltmhet9h:anedsiumleftohnyaltneit(r2omsaMminien (H0a.n5k'msMbailnanHcaendk'ssalbtasloalnuctieodn,salt solution, without calcium and magnesium). RESULTS Cefyftioctioexnciycwcaosncseenetnraattitohne:hIinghrearngceofnicnednitnrgattieostnss(otmeset rmeadtuercitailonpriencciepliltagtreodwatthhaingdhecsltoning concentration Genotoxic effects: No consistent evidence of genotoxicity seen with or without $9 [-------- vat : 000257 |Cm `Concentration | ColmCE at Day 0 |CoO[ee CE at Day 3(%)| Mutation Frequency f[SoolemComal h[1e00 fTee T{z33s p fo sf h0 wpft Jh ee e s Ts; ] ] [postiveContr BMS)[129 Jo {159 | f[Sm ooentConrol 100 y {ss airs Ee C J e J e I p[Posoitive Contol DMN)f[ee 30r [3 a Tog | [fSF lovoemConrole [1e0s0 efa [ee[ s 5 s {s5 o ] f 5 off e f as [PositiveControl(BMS) [94 [or {70 | f[Sp f oolvenComal e [100e w Tos m pi 5 y e 3] ] Cfpo olsoiveControl@MN)f [41 o om TaJ or a r f 3g sia] ] CONCLUSIONS N-MeFOSE was not mutagenic in the L5178Y mouse lymphoma gene mutation assay. REMARKS `The protocol used for this study differed in several ways from normal practice. These differences include: use ofrather high levelsof S9 mix (20%); use ofa positive control chemical b(eEtMwSe)enfosrmtahlel-noann-dacltairvgaet-icoonloansysamyuttahanttsi;ndauncdesusfeeowfa"snmaulnlu-scuoallolnyy"lomnugtamnuttsa;ntnoexdpirfefesrseinotniapteiroinod (3 days). REFERENCE an Ves NOTOX. 1994. Evaluation of the Mutagenic ActivityofT-5874 in an Jn Vitro Mammalian Cell Gene Mutation Test With L5187Y Mouse Lymphoma Cells (With Independent Repeat). 000258 NOTOX Project 115921; NOTOX Substance 38187 On iitAssessment RepApopernd t vi 000259 ROBUST SUMMARY - RS25 Title: 1993 MUTAGENICITY TEST ON T-5711 IN AN IN VIVO RAT MICRONUCLEUS ASSAY, TEST SUBSTANCE Identity: N-Methyl perfluorooctanesulfonamido ethanol (N-MeFOSE) Remarks: (T-5711). ACrseeapmar-actoelodroecdumgeranntul(aMremmatoerfiralo;m pBu.rCi.tyCnooptlereypotrotRe.dD;. IdHeonwteiflilcsa,tiSoen:ptLe-m1b2e7r614, 1995, KMeeyFtOoSFECaanldcoshmoalllTaomxoSuanmtpsle(s~)5%idoenrtilfeisess)otfhirselaast"ewdifdleuorraoncghee"miMccaFlsO,SpEa,rticcounltaarilnyisnhgor8t3e.r8c8h%aiNn- (Cy, C5, Cy, C, C;, and C,) analogs. METHOD Method/guideline: FIFRA Guideline 84-2 Test type: In vivo rat micronucleus assay GLP: Yes Year study performed: 1993 Species/Strain: Charles River Sprague-Dawley rats. Sex: Male and female No. Animals: S/sex/dose Route of administration: Oral gavage in 0.5% carboxymethyleellulose suspension. Doses/concentration mike). levels: 1250, 2500, and 5000 mg/kg in 0.5% carboxymethylcellulose (10 Frequencyoftreatment: Single dose; subgroups examined after 24, 48, and 72 hous. cSetlaltsiswtiitchalmmicertohnoudcsle:i,AnfaollylsoiwsedofbyvaTruikaenyc'esoSntsuqdueantriezreodotraanrgcesitneest-twriatnhsfaodrjmuesdtmperonptofrotriomnusltoifple comparisonsifsignificant. RAneimmaarlkss:werAedurlatndraotmsi(zaepdpraonxdimwaetieglhyed wpreieokrstoolddo)siwnegr.eGqruoaurpasntoifne/dsefxo/rd7osdca/yhsarpvrieosrtttoismteudwye.re ausserde,ppllaucsemaenntadsdfiotrioannailmSa/lssetxhtahtatdireedcperiivoerdttohecehlilghhardvoesste.oftFeisvet mcaolmepsoaunnddftiovebefeumsaelde,sirfenceeeidveidn,g vweehriecleexaamndinpeodsiattiv2e4choonutrrosla(ftceyrcdloospihnog.sphAalmliadnei,m6a0lsmwge/rkegoibnssetrervielde diemimoendiizaetdelwyataefrt,er1d0omsli/nkgg) and periodically throughout the study for signs oftoxicity. Tibial bone marrow was recovered at rf niaAssReepnosAppend var 000260 Gthreundewsailgdnastoelduthiaornvefsotlltoiwmeedabnyd Gsepirmesaad.onCsoldideeds,sfliidxeesd winermeetahnaanloylz,edanfdorsPtaCiEne/dNwCiEthraMtaioy-and 1,000 PCEperanimal were scored for micronuclei. RESULTS Toxicity: No significant bone marrow toxicity was seen, based on the PCE/NCE ratio. dGoesneo.toTxhiecpeofsfietcitvse: cNoentgraotlivpero-d-uncoedintchreeaesxepeinctmeidcrsoingnuicfliecaatntedinpcorleyacsherionmamtiiccroenruyctlherioccyotmepsaarteadny 0 controls (2.24 0.64% v. 0.12 females). 0.05% in males and 2.22 0.33% v. 0.02 0.02% in aRneimmaarlkssf:roTmox4i7cihtoyurinstahfetehridgohs-idnogsetogtrhoeupenwdaosftehviedesntcudeyd abnydablyantghueiddeaatphpseaorafancteootafl tohfefour males and two females among the primary and secondary female was found dead at 47 hours after dosing. high dose groups. Also one mid-dose CONCLUSIONS N-MeFOSE alcohol erythrocytes. was negative for inducing micronuclei in rat bone marrow polychromatic REFERENCE WMuarslhii,ngH.ton1,99V3i.enMnuat,aVgeAni2c2i1t8y2T.esFtinoanl TR-e5p7or1t1,iAnparinlJ3n0,Vi1v9o93R.atHMiWcAronSutculdeyuNsoA.ss1a5y5.15H-a0z-l4e5t4o,n rat nialsss Report Appeic vas 000263 ROBUST SUMMARY -RS26 DTiNtlAe:SGYENNTOHTEOSIXSICAINTDY CTEELSLT OPRNOTL-I5F71E1R.A1TIINOTNHAESISNAVYISVOI/NIRNAVTITLIRVOEURNCSECLHLSE,DU19L9E3D TEST SUBSTANCE Identity: N-Methyl perfluorooctanesulfonamido ethanol (N-MeFOSE) Rdoecmuamreknst:(CMreemaom-fcroolmorBe.dC.grCaonupllaerymtaoteRrDia.l;HIodweenltlifsi,caSteipont:emT-b5e7r111.4,1,19L9-51,27K6e.yAtoseFpCaraatlec:ohol sTmoaxllSaammpoluenst)si(de~n5t%ifioersltehsiss)oafsr"ewliadteedrafnlgueo"roMcheeFmOicSaEl,s,cpoanrttaiicnuilanrgly83s.ho8r8t%erNc-hMaienF(OC,S,ECa,ndCy, C,, C,, and C,) analogs. METHOD Method/guideline: Williams 1980, Mirsalis et al. 1982; Butterworth 1987 `Test type: In Vivolln Vitro Unscheduled DNA synthesis and cell proliferation in rat liver cells. `Test System: Primary cells from animals dosed in vivo GLP: Yes Year study performed: 1993 Species/Strain/cell (CRLCD BR). type/cell line: Primary hepatocytes from male Sprague-Dawley rat Metabolic activation: NA pSrtoaltiifsetriactailonmeatshsoayd:s:onFeo-rwUayDaSnaalsyssaiys:ofPvraorciedaunrceeoffoClalsowceidanboyaDnudnnGeaty'lsort-(te1s9t8(3r).anFkor cell transformationof data was performed ifvariances were hetcrogencous). REMARKS Study Design: UDS Assay: m`aGtreoruipasl.oAf3ddriattiso/ndaolseg/rtoiumpespooifntthrreeceerievceediavesdintghleevoerhailcgleavoargpeosdiotsievoefcoonnteroolf.thTriemeepdooisnetssofwteerset2- o3bhtoauirnsedabndy p1e5r-f1u6sihoonuorfsraafttelridveorsiinngsiwthuewnithhecpaaltcociyutmeasnwdermeaghnarevseistuemd.freHeeHpaatnokcsytbeaslawnecreed salts Hcoenpteasinbiunfgfe0r.,5pmHM7.2e,thfyollelnoewgeldycboyl-5b0i-s1(0B0-aumniintose/tmhiyoleftchoelrl)a-gNenNa-sieetirnaaWcieltliicaamcsidMe(dEiGuTmA)Eand (WME). Cells were cultured in WME with 10% fetal bovine serum (FBS) in culture dishes containing plastic coverslips. After incubation for 2 hours at about 37C to allow attachment, Dra tlAssRepeortnAppetnd V ver 000262 turniattiattaecdhtehdycmeildlsinweer(4e7rCeim/omvmeodlea)n.d cAufltteurreamlaebdeiliunmg rpeeprliaocdeod fw4ithhouWsM,Ecelclosnwtearineirnegfe1d0uwCiit/hml WME + 10% FBS containing 0.25 mM then swollen by addition of 1% sodium thymidine citrate for and 7-10 incubated for 18-19 minutes, ces were hours. Nuclei fixed in acetic were acid: aetshsaensosled(1b:y3)c,oaunndtidnrgiend.uclFeiaxregdracionvserasnldipssuwblerraectpirnogctehseseadvefroargaeutnourmabdieorgrofagprhayi.nsUDinSnuwcalseus- csiozveedrsalriepas(o3 fcocvyetrosplliapssm/.aniTmhale) nweetrneucmleeaasrugrreadinacnoduantvseroange5d0froarnedaocmhltyresaetlemcetnetdccoenldlistipoenr. Doses: 250, 500, 1000 mg/kg Number of replicates: One Animals/dose: Three per timepoint (2 timepoints). Solvent: Con oil (10 ml/kg) Positive controls: Dimethylnitrosamine, 10 mg/kg. fCoerlhliPgrhoelsitfedroastieoannAdsspaoys:itiGvreocuopnstroofl)fiwveeryeoduonsgemdaalsefaodrutlhteCUrDlS:CaDsBsRayS7p2arhaoguures-bDeafwolreeysarcartisfi(c4e. sAutbcaubtoaunteotuheslsya(mdeortsiamlesu"rtfharecee)dwaiytshprainorAltzoestac2rMifLi1ce,o"stmhoetsiecapniummaplslwoeadreediwmiptlhan2tmedl of BrdU csoonlturtoilo)n w(e2r0emgr/emmlo)v.ed72anHdoufirxsedafitnerneduotsrianlg,bulfifveerreadndfoarmcarloisns.-sePcatriaofnofifn-deumobdeeddneudms(elcatbieolnisn(g5 pprme)pafrredo.m tCheelllepfrtollaitfeerarla,tiroinghwtamseddeitaenc,teadndimrmiughntohanitsetroicorhelmoibceaslalnydwfirtohmDdAuBodsetaniun.m wOenrce:e oapnpralolprthiraetee lsitvaeirnilnogboefs edxuaomdiennedu,mcsoeucnttiionnsg owfaslacboenlfeidrcmeeldl,s waands sptearifnoirngmewdausscionngftihremleedftaslasteirmaillar 8lobmei.crAotslceoapset 2fi0e0l0dsn(uscelleeictpeedraatnrimaanldowmerbeyecxoammpiunteerd)fpreormsaecmtiionn.imumof three sections, covering Doses: 625, 1250, 2500, 5000 mg/kg Numberofreplicates: One Animals/dose: Five. Solvent: Corn oil (10 ml/kg) Positive controls: Dimethylnitrosamine, 15 mg/kg. RESULTS Genotoxie Effects: any dose (see Table No 1). increase in net nuclear grains o%r cells with > 5 net nuclear grains at Cell Proliferation Effects: the two highest doses) was A dose-related increase observed (see Table 2). in labeling index (statistically suignificant at Remarks: There were no test-specific confounding factors raf nisss Report Appents vo 000263" Table 1 Control me 0920.41 0.11020 Ulm 250 mg/kg -0.15035 0.03035 500 mg/kg 023020 0610.58 -0170.15) 0.790.57 fem 0.170.15 0,890.01 -0.37:+ 0.48 0.520.05 0.91022 eC Nea 4.00 1.34 Aon 007 ER 267 133 33 000 100 067 333 0.00 200 0.00 FE EEE EOL E 1000 mg/kg 0.36% 0.51 -0.580.36 2.00 0.00 006+023 0020.14 1.00 Loo Positive Control | 17.98 2.06 03998524028664 9056373 0380607 (DMN 10mg/kg) | 0947.98 4054338 36.00 38.00 Table 2 |__Dose TT LabelingIndex(%) | LiverWeight(z) |TerminalBodyWeight(9) | (DMN 15 mg/kg) CONCLUSIONS pNr-olMifeeFraOtiSoEn.alcohol was negative for inducing unscheduled DNA synthesis, but did cause cell REFERENCE Cifone, M.A. Synthesis and 1993. Genotoxicity Test Cell Proliferation Assay On T-5711.1 in the in Rat Liver Cells. In Vivo/In Vitro Unscheduled Hazleton Washington, Vienna DNA. VA 22182. Final Report, September 14. HWA Study No. 15515-0-494 Submitted to 3M `Corporation, St Paul, MN 55144-1000. Dra tilAssam Bor Append V var 000264 ROBUST SUMMARY- RS27 Title: DetectionofFluorochemicals in 35 Lotsof Commercial Sera, 1999 TEST SUBSTANCE Identity: PFOS Remarks: METHOD Study design: Cross-sectional data on PFOS detected in 35 lotsofindividual or pooled human sera samples from US chemical or biological supply companies. Manufacturing/Processing/Use: N/A Hypothesis tested: To determine the levels of PFOS in the serumofthe general population. Study period: 1999 Setting: N/A `Total population: 35 lotsofindividualorpooled human sera samples from US chemical or biological supply companies. No other information provided. Subject selection criteria: Not provided in report. Total# of subjects in study: Approximated--see "total population" above Comparison population: N/A Participation rate: N/A Subject samples description: were taken. No information was provided on the individuals from whom the sera Health effects studied: PFOS levels in blood Data collection methods: Blood sera samples Details on data collection: stored, analyzed, etc. No information was provided as to how the blood was drawn, Exposure period: Unknown. PFOS serum levels used as surrogate for exposure. [---------- 2 oozes Description/delineationofexposure groups/eategories: N/A Measured or estimated exposure: N/A Exposure levels: N/A Other methodological information: RESULTS Describe results: The mean PFOS serum level was 35 ppb, with a range of5 to 85 ppb. Study strengths and weaknesses: These data are only preliminary cross-sectional data used to determine PFOS levels in the general population--no other descriptive information about the subjects was collected. The blood serum collected is from 2 small pool. Geographic regions were not specified. Other demographic considered representativeofthe general information was not available. populationofthe US. Blood donors cannot be. Research sponsors: 3M Environmental Lab Consistencyof results: N/A CONCLUSIONS NA REFERENCE Supplemental Notice on Sulfonate-based and Carboxylic-based fluorochemicals. Analyses of blood sera samples from the general population. 37. May 26, 1999. 3M Company. SEHQ-0699- OTHER Dra itlsessReport Append va 000266 ROBUST SUMMARY - R$28 Title: AnalysisofPooled Blood Samples from 3 European Blood Banks TEST SUBSTANCE Identity: PFOS Remarks: METHOD SintuthdryeedeEsuirgonp:eaCnrocsosu-ntsreicetsi:onBaelldgaituamo,nNPetFhOerSladentdescatendd in pooled Germany. serum from blood banks Manufacturing/Processing/Use: N/A Hypothesis population. tested: To determine the presence of PFOS in the serumofthe general Study period: 1998 Setting: N/A TBoetlagliupmopbulloaotdiobna:nkSperrouvmidpeodol5epdoforleodm s3armepglieosna(l10bldooondorbsanpkesr sinamtphlree)e.EuTrhoepeNaenthceorulntarnidss. The, sample pooled provided 6 pooled samples (10 donors per sample). samples (30 donors per sample). Altogether, these The Gremany blood ank proivded 16 pooled sampled represented 290 6 donors. `Subject selection criteria: Telephone request. requested but permission was not granted. Other European country blood banks were Total# of subjects in study: Approximated--see "total population" above Comparison population: N/A Participation rate: 50% response Subject description: No sera samples were taken. information was provided on the individuals from whom the . Health effects studied: PFOS levels in blood Data collection methods: Blood sera samples Details on data collection: drawn, stored, etc. No information was provided as to how the blood was DraIntlsss por ppeic vas 000267 Exposure period: Unknown--PFOS serum levels used as surrogate for exposure. Description/delineation of exposure groups/eategories: N/A Measured or estimated exposure: N/A Exposure levels: N/A Statistical methods: Means calculated. Other methodological information: RESULTS D(reasncgrei4b.e9r-e2s2u.l2tsp:pbT)h.eTmheeanmesaenrusmcrPuFmOPSFlOeSvellefvoerl tfhoer 5thBee5lgNieutmheproloalneddpsoaolmepdlessamwpalses17wpapsb53 ppb ppb (range (range 39-61 ppb). 32-45.6 ppb). The mean serum PFOS level for the 6 Germany pooled samples was 37 SintiutidalyPsFtrOeSngltehvselainndtwheeagkenneersaslesp:opulTahteisoen-d-antoaoatrheercrdoesssc-rsiepcttiivoenailnfdoartmaautsieodn taoboduettetrhmeisnuebjaencts wbaanskcsolcloencttaedc.tedBdliododnostepraurmticwiapastec.ollPeFctOeSd flrevoemlsonvlayri3edbbloyogdebogarnakpshi--cortehgeironE;urhoopweeavnerblwohoedther ntohitskisnotowngeaosgrtahpehilactatlerdwiaffserneontceasvaoirlatbolet.heBdleomoodgrdaopnohrisc ccahanrnaocttebreisctoincssiodfertehderpeoporleesedndtaotniovresoifs the general population. Research sponsors: 3M Medical Department Consistency of results: N/A CONCLUSIONS NA REFERENCE OTHER raf niaAssam Report Append vas 000268 ROBUST SUMMARY- RS29 Title: Analysis of Pooled Blood Samples from 18 U.S. Blood Banks TEST SUBSTANCE Identity: PFOS Remarks: METHOD Study design: Cross-sectional in different regionsofthe US. data on PFOS detected in pooled scrum rom blood banks Manufacturing/Processing/Use: N/A Hypothesis tested: population. To determine the presence of PFOS in the serumof the general Study period: 1998 Setting: N/A Total population: the US. There were Serum pooled 68 pools and from 18 regional blood banks an estimated 340-680 donors. in various geographic regions in Subject refused. selection eriteria: Many blood banks were approached to participate, but manyof them `Total #of subjects in study: Approximated--see "total population" above Comparison population: N/A Participation rate: 50% response Subject description: No sera samples were taken. information was provided on the individuals from whom the Health effects studied: PFOS levels in blood Data collection methods: Blood sera samples Details drawn, on data collection: stored, etc. No information was provided as to how the blood was Exposure period: Unknown--PFOS serum levels used as surrogate for exposure. raf nia ssessmen Report Append vas 000269 Description/delineation of exposure groups/categories: N/A Measured or estimated exposure: N/A Exposure levels: N/A Statistical methods: Means calculated. Other methodological information: RESULTS Describe results: PFOS serum level PFOS across serum levels varied by geographic location. The overall mean pools was 29.7 ppb. The range across geographic regions was 9 ppb (Omaha, NE) to 56 ppb (Greenville, SC). The rangeofthe averages was 14 to 52 ppb. Study strengths and weaknesses: These data are cross-sectional data used to determinane initial PFOS level in the general population--no other descriptive information about the subjects `was collected. contacted did Blood serum not participate. was collected PFOS levels from only varied by 18 blood banks--hoaflthfe geographic region; however blood banks whether this is to geographical differences or to the demographic characteristics of the pooled donors is not k`gneonewrnal apsoptuhlealtaittoenr owftahsenoUtSa.vailable. Blood donors cannot be considered representativeof the Research sponsors: 3M Environmental Lab Consistency of results: N/A NA CONCLUSIONS REFERENCE Perfluorooctane sulfonate: Current Summaryof Human Sera, Health and Toxicology Data, Jan. 21,1999, 3M Company. 8EHQ-0299-373 Buxton B, Struass W, Chang O. Working Memorandum on Data Quality Assessment. Columbus (OH): Battelle Laboratory, September 22, 1998. OTHER Or mtdesert Append wr 0002770 ROBUST SUMMARY - RS30 `Title: Analysis of PFOS from Pooled SerumofTwo Commercial Laboratories, 1998 TEST SUBSTANCE Identity: PFOS Remarks: METHOD Study design: sources. Cross-sectional data on PFOS detected in pooled serum from commercial Manufacturing/Processing/Use: N/A Hypothesis tested: To determine levels ofPFOS in the serumof the general population. Study period: 1998 Setting: N/A `STiogtmaal)p.opTuhlearteiowne:reSaipxpproooxliemdatseelrya s5a0m0pliensd,ivoibdtuaalisneidn fthreomdo2nocormpmoeorlcsifarlosmouIrntceersg(eInnatenrdgean and minimumof 200 donors in the pools from Sigma. Subject selection participate. criteria: Ii was not reported how these sourcesofblood were identified to `Total#ofsubjects in study: Approximated---see "total population" above Comparison population: N/A Participation study was not rate: The provided. total numberof commercial sources approached to participate in this. Subject samples description: were taken. No information was provided on the individuals from whom the sera Health effects studied: PFOS levels in blood Data collection methods: Blood sera samples obtained from 2 commercial sourcesofblood Details on data collection: stored, analyzed, et. No information was provided as to how the blood was drawn, Dra nial sss Report Append vas 000271 Exposure period: Unknown. PFOS serum levels used as surrogate for exposure. Description/delineation ofexposure groups/categories: N/A Measured or estimated exposure: N/A Exposure levels: N/A Statistical methods: Means calculated. Other methodological information: RESULTS DPoeoslcsr.ibTehrees3ulptoso:lsPFfrOoSmsSeirgummalceovenltsaiwneerdeP43F,O4S4,atanldev4el4spopfb2(6,me2a8,n a=n4d44p5ppb)pbfr(ommeathne=3 3I3ntpeprbge)n Study levels strengths and weaknesses: These in the general populationof the US. data It is cannot be considered representative of the a small sample and no other descriptive PFOS iwnefroermnaottiaovnaialbaboluet. thTehseusbejedcattsawsahsouclodlloenctleyd.beGuesoegdraasphaipcrealnidmoitnhaerry daneamloygsriasopfhgiecnienrfaolrmlaetvieolsn of PFOS levels in blood in aspecified human population. Research sponsors: 3M Environmental Lab Consistency of results: N/A CONCLUSIONS NA REFERENCE PJearnfulauroyr2o1oc,t1a9n9e9,su3lfMonaCtoe:mpCaunryre.ntSESHuQm-m0a2r9y9-o3f7H3u.man Sera, Health and Toxicology Data, OTHER rat niasess Report Appeic vo 000272 ROBUST SUMMARY - RS31 `Title: 1999 A Pilot Study to Identify Fluorochemicals in Children With Limited Sera for Analysis, TEST SUBSTANCE Identity: PFOS Remarks: METHOD Study design: Cross-sectional pilot data. Manufacturing/Processing/Use: N/A Hypothesis tested: To could be used on a small determine that the volumeofserum. analytic technique used to test PFOS in human serum `fTlhueorobojcehcetmiivcealosfitnhea sstaumdpylteoofbcehciolmdprleentteodpirsotvoiddeetaermmoirnee stpheecisfeircuumndceorncsetnatnrdaitnigoonfstohfeselected. distribution of these compounds in children. Study period: Child sera samples were samples were analyzed in Spring 1999. collected from January 1994 to March 1995. The sera Setting: N/A `Total population: n= 10 SMuibnjneecstotsaelDeecptiaorntmcerintteorfia:PedTihateriscesr.a sTahmepylewserweeroebtparionveiddefdrotmo 3a Mlarbgye tchleinUincailvetrrsailtoynoGfroup A cshtirledprteoncopcrcealseinntfeedctwiiotnhs siingcnhsiladnrdens.ymTphteocmhsilodfreancuwteer-eonrseestidpheanrtysnogfi2ti3s.stAatlelsoifn tthheecUhSi.ldrTehnehsaed positive throat cultures at the initial visit Total #ofsubjects in study: n= 10 Comparison population: N/A Participation rate: N/A Subject description: samples were taken. No information was provided on the children from whom the sera Health effects studied: PFOS levels in blood Dra iilsss Ror Append va0 000273 Data collection methods: Blood sera samples pDreotcaeidlusroen. dTahteaecxotlrlaeccttsiown:ereSeqruaanstaimtaptlievselwyearnealexytzreadctfeodr PusFiOngSaunsiinogn-hpiagihr-ipnrgeesxsturraectliiqounid cQuharloimtaattoigvreaapnhayl/yesliescwtraosspcroanydutcatneddebmymcaosmspsapreicntgropmeeatkryreasnpdonesvealiunattheed svaemrpslusesantoetxhtartacotbetdaicnuervde. wfarosmbsatsaenddaorndsr,eawshoennabploessHiPbLlCe-.reIfstetnatnidoanrdtimmaetearnidalprweadsicntoetd amvaasilsabslpee,cctroommpeoteurndreisdpeonntsief.icaLteisosn than 100 uL_of sera were available for analysis. The limitof detection was 3 ppb. Exposure period: N/A Description/delineation of exposure from children 6 - 12 years old. groups/categories: Blood sera samples were collected Measured or estimated exposure: N/A Exposure levels: N/A Statistical methods: Means calculated. O`Tthheemretmheotdhoddeotleocgtiiocnalliimniftsoramraetsiiognn:ifiTchanetlsymahlilghsearmtphlaenvroelpourmteedpoisneedarlainearlysttiucdailesr.estrictions. RESULTS Describe results: average level was PFOS 54 ppb. scrum levels in these 10 These individual levels children ranged are higher than from those 31 to 116 ppb. The reported in pooled samples in adults (29-44 ppb) in the general population. samples is ongoing. A study analyzing over 600 pediatric Study strengths and about the subjects. weaknesses: Very small number of samples, no descriptive information Research sponsors: 3M Environmental Lab Consistency children. of results: To date, no other data have been collected on PFOS serum levels in CONCLUSIONS Tothheerauctohnocrlsuscioonncslucdaen tbheatdrPaFwOnSacbaonutbtehdeelteevcetlesddientevcetreydsimnatlhlisvosmlaulmlessoafmpsleeroufmc,hibludtretnh.at no REFERENCE Lr -------- var 000274 LEanbvoirraotnomreyntRaelpoLratb,orAantaolryys.isoRefpoFrCtsNion.SFamApClTe-sGoEfNC-h0i1ld1ren's Sera, May 21, 1999, 3M OTHER The samples analyzed in small volumes of serum. this pilot project were collected to verify the analytic technique used on [-------- v2 00027s ROBUST SUMMARY- RS32 T(iPtFlOe:S;2T66-2W9e5e)kiCnaCpysnuolmeoTlogxiucsitMyonSktuedyys,wi2t0h0P0erfluorooctane Sulfonic Acid Potassium Salt TEST SUBSTANCE Identity: PFOS; T-6295, FC-95, CAS #2795-39-3 Remarks: Lot 217, white to off-white powder, stored at room temperature. METHOD Method/guideline followed: Twenty-six week treatment period, followed by 52 weeks recovery. Study duration: 78 weeks GLP (Y/N): Y Year study performed: 2000 Species/strain: Cynomolgus monkeys Sex: Males and females Number of animals/sex animals per for group 2. dose group: 6 animals/sex/dose group for groups 1, 3, and 4; 4 Route of administration: Oral capsule Doses tested and frequency: 0 mg/kg/day, 0.03 mg/kg/day, 0.15 mg/kg/day, or 0.75 mg/kg/day Post-observation period: 52 weeks Statistical ANCOVA, mceotvahroidasteu-asdejdu:stLeedvemneea'nss,te5st%fotrwov-atraiialnecde homogeneity: ANOVA, probability level Dunnett's t-test RESULTS NOAEL (dose and effect): 0.15 mg/kg/day. LOAEL (dose and effect): 0.75 mg/kg/day. Death, liver effects, effect on cholesterol Tloixviectorrebsopdoynswee/iegfhftecptesrcbeyntdaogsees,lelvievle:r D(0eabtrhaiantw0e.i7g5htmgr/aktgio/sdainy;feimnaclreesasaetd0a.b7s5olmugt/ekgli/vdearyw;eight, alboswoelruttoetaalndchroelleasttievreolliavenrdwleoiwgehtr;hiMgahledsenasnitdyfleimpaolpersotieninthceho0l.e7s5temrgol/,kgl/ivdearyordgoasen-wgerioguhps.had r-------- "000276 S0t.a7t5ismtgi/ckalg/rdesauyltfse:maTlheetdriefaftemreenntcegrinouwpesigwhatsastttathiesteincdaollfytsriegnaitfmiecnantt;betthweeeefnfetchteocnotnottraoll and the csthaotliessttiecarlollyasnigdnihfiigchandte;nisnitmyalliepsopirnottheein0.ch7o5lemsgt/ekrgo/ldianytdheos0e.7g5romugpkgth/edloisveergorroguapnwwaesights and twheeigohrtgsa,n-tthoe obrogdayn-wteoi-gbhotdypewreciegnhttagpeesrwceenrteasgteatainsdtictahlelyorsgiagnni-fbircaainntwaenidghint freatmiaolsewsetrhee allilver significant, Rsteumdya.rkAst:thMeaelnedsowfei26ghweedc3k.s3-o3ft.r4ekagtmaenndt,femmaalleesswweeiigghheedd 32..78,-23..89,k3g.5a,tatnhde b3e.3gikngnifnogrotfheth0,e 02..083k,g0.f1o5r tahned00,.07.503m,g0/.k1g5/daanyd t0r.e7a5tmmegn/tkggr/oduapystrreesaptemcetnitveglryo.uFpesmraelsepesctwievielgyh.edTh3.e1,di3f.f1e,r3e.n1ceand bAetttwheeeenntdhoeftcohnetrroelcaonvdertyhepe0r.i7o5d,mdgi/fkfge/rednacyesfeimnawleeitgrhetabtmeetnwteegnrotuhpescwonatsrosltaatnisdtitcraelaltyesdiganniifmiacalnst. `were no longer obvious. `diTewdoamfatleresdofsrionmg tohneD0a.7y5 1m5g5/k(gW/edeaky 2g3r)o.uCplidniidcanlotsisgunrsvinvoetetdo tihnethsicshaendiumlaeld sianccrlifuidceed.:Oconnestarniicmtaedl phuyppiolasc,tipvailtey,gulmasbo,refdewr,esmpuicroaitido,n,lidqeuhiyddraantdiobnl,acakn-dcorleocruedmbfeencets,polsoitwiofno.oIdncaodndsiutmiopnt,iotnh,e animal wdeatsercomlidnetdo ttohebetoupcuhl.moAnnareynlnaercgreodsilsivweirtwhassevdeerteecatceudtebyinpfallapmatmiaotni.onC.auOsneodfayde1a7t9h, wthaessecond male was sacrificed in a consumption, excessive moribund salivation, condition. Clinical signs noted included low labored respiration, hypoactivity and ataxia. food Causeofdeath `was not determined. Mfeamlaelsesanidn tfheema0l.e1s5 ianndth0e.07.575mgm/gk/gk/gd/adyaygrdoouspes-ghraoduphihghaddelnoswietrytloitpalopcrhootleeisntecrhoolleasntedromlalleoswearnd tmheaansucronetdroolnlayt tohnedtawyost1i5m3e apnoidnt1s82i,t waands nmoeapsruerdeodsidnugrivnagluterseaatrmeeanvta.iHlaDblLe cfhoorlceosmtepraorliswoans for eTahcehedfofescet gornoutpo.talHcohwoelevsetre,roolnwlyasthreevefefrescetdiwnitthhein0.57w5 emegk/skgofgrreocuopvewraysasntdattishteiceaflfleyctsiognnihfiicgahnt. density lipoprotein cholesterol was reversed within 9 weeksofrecovery. oEfsvtarraidaitoliovna,lounelsywethreedlaoywe1r82invmaallueeswagisvesingn0i.f7i5camngt./kEgs/tdraoyneonvadlauyess 6w2e,re91g,eannerdal1l8y2hbiugthebrecianutshee tvraelauteesdwfeermealseisgnoinfidcaanytsly37di6ff2eraenndt.91Trbiuitodaogtahiynrboencinaeusveaolfuveasrwiearteionnotianbtlhye ldaotwae,rnoonnedoafysth9e1seand h1o82rmionnmealveasluaensdinfetmreaalteesd ggirvoeunps0.w1e5raenddif0f.e7r5enmtg/fkrgo/mdtahyo.seoTfhecroentwreorles obtuhterthienssetadnicfefserienncwehsicwehre: nreoltacteodnstiosttehnetaodvmienritsitmraetoironboefttwheeentessetxemast,erwiearl.e nAoptpcalreeanrtlydidfofseer-ernecleasteidnatnhed sdeixdunaoltmaaptpuerairtytoofbe. Abdodtihtimoanlaelslya,nndeiftehmearlmesaluessednoirn tfheemaslteusdyincothmepl0i.c1a5tdesostehegrinotueprphraedtattriionioofdotthhyerhonoirnmeovnaeludeast.that differed from predosing values at any time during the study, and variations in triiodothyronine Dra itlsesResport Append V vas 000277 levels were not histopathologic accompanied changes). by other indicationsofthyroid effects (TSH or T4 level, or Awetitgehrtm,ilniavlersa-ctroi-fbiocde,y fweemiaglhetspeinrctehneta0g.e7s5,magn/dkgl/ivdeary-tdoo-bsrea-ignrwoeuipghhatdraitnicors.eaIsnedmaalbesso,lultievelri-vteorbody wlieviegrhstweperrecoebntsaegrevsedweirnetwionchriegashe-ddoisnetmhaelheisgha-nddosien gonreouhpigcho-mdpoasreefdemtaolteh.eOcfotnthreolts.wo"mMaoltetslendo"t shuirgvhi-vdionsge umnatillesth(eisncclhueddiunlgedthtoesremithnaatldsiadcrniofitcse,urovnievehatodsac"hmeodtutlleedds"acarnidfilcaer)ghealdivceern.tTrhirloebeuloafr4or diffuse hepatocellular hypertrophy which was also Centrilobular or diffuse hepatocellular vacuolation observed occurred in in all high-dose females. 2of 4 females and 2 of4 males in the high-dose group. No PFOS related terminal sacrifice lesions were reversible. observed at recovery sacrifice indicating that the effects seen at This been is a draft report completed. that willbe finalized afer electron microscopy and light microscopy have CONCLUSIONS cPhFolOeSstiserotlo,xiacndtoecfyfencotmionglgloivuesr wmeoingkhetyasndatc0a.u7s5inmgg/hkepga/tdoacyelclauulsairnhgydpeeartthr,opalhtyeraantdiovnsaciunoltoattailon in breovtehrstirbelaetewdimtahilneds waenedkfsemfaolretso.taHlocwheovleesrt,ertohle, e9ffweecetsksonfocrhoHlDesLtecrhoollaesntdertohle,lainvedrwaiptpheianrato27be `week recovery period for microscopic liever effects. Remarks: None REFERENCE TPhootamsfsoirudm,SPaJl.t((2P0F00O)S.;2T66-2W9e5e)kinCaCpysnuolmeoTlogxuisciMtyonSkteuydsy.wiUtnhauPdeirtfelduoDrroaofcttaFnienaSlulRfeopnoirctAPcriedpared for 3M, St Paul, Minnesota April 12, 2000. 502 pp. by Covance Laboratories, Inc., Madison Wisconsin 53704-2595. OTHER raf nial sscssmet Report Appenic vas 000278 ROBUST SUMMARY - R$33 Identity: N-Ethyl Perfluorooctanesulfonamido Ethanol (N-EtFOSE alcohol) Remarks: Fluorochemical FM-3924, Lot No. 547 METHOD Method/guideline: None Test type: 104 week oral toxicity study GLP: No Year: 1987 Species/Strain: Rat; Sprague-Dawley [Cr:COBS CD(SD)BR] Routeof administration: Oral (in chow) Doses/concentration levels: 0, 10, 30,100 ppm N-E(FOSE alcohol Sex: Male & Female Exposure period: 104 weeks Frequency of treatment: ad libitum Control group and treatment: Concurrent vehicle Post exposure observation period: None Duration of test: 104 weeks Sctoantsiusmtpictailonm,etahbosodlsu:teBaarntdlertetl=astitveestofrogranvawreiiagnhctesh,oamnodgeotnheeirtylawboarsatuosreyddfaotra;biofdtyhewediagthatws,erfeeendot sIifg,nhiofiwceavnetra,t Bpa=r0t.l0e0t1t,=sttheestdawtaaswseirgeniffuirctahnetraatnpal=yz0e.d00u1s,itnhgeadattwoa-wteairleedraDnuknendetatnd=sattewsot-(tpai#l0e.d05). oDrugnanne/tltes=isotnesctlawsasisfipceartifoonr.meAdpon=t0h.e05ranskisg.nifAicatnwcoe-tlaeivleeldwFiitshheBro=nsfeErxraocnti=Tessatdwjuasstmuesnetd ffoorr each meualcthicpellelcwoamspagrrieastoenrstwhaans2u0s,edthweinthYiantecsa=chcoorrrgeacnt/eldesCihoin-/Ssqexuacraetetgeosrtyw.asIftusheed.expected value of Remarks: Test Subjects: Age at study initiation: 39 0 41 days Weight at study initiation: (Mean) Male: group, 165.3 g for 168.2 g for control group, 165.6 100 ppm dose group g for 10 ppm dose group, 169.1 g for 30 ppm dose Female: 138.2 `group, 138.7 g for control for 100 ppm group, 135.6 dose group. g for 10 ppm dose group, 135.8 for 30 ppm dose No.of 50 per animalsper sexper dose: sex in 30 ppm dose group, 65 65 per per sex sex in in control group, 100ppm dose 50 per group sex in 10 ppm dose group, fr -- vs 000279 Study Design: Vehicle: Chow tSarteealtleidtaengdro3u0pwsiathndthreeacosnotnrsolthreatys)w. erDeuraidndgedt:he6f0irusnttwreeeakte,dasten1 tminoenltrhatasn(d30ath3oumsoendthwsi,th5 the animals per sex were sacrificed and plasma samples were analyzed for organic fluorine. EClaicnhicaanliombaslewrvaastiroenmsopveerdfofrrommedcaangde afnrdeqeuxeanmciyn:eOdbosnecrevewdeefkolry.morFboiodditcyo/mnosruimbputnidointydadtaailyw.ere collected for Weeks 1 through determined weekly for the first 16 and once ever4y weeks 6 monthsoftreatment and thereafter. once every Body weights were 2 weeks thereafter. Eye `coenxtarmoilnaatnidonhsiugshidnogsiendriartescptroioprthtomotrsecaotpmeynat,nda/toarpsplritoxliammaptebliyomoinceroyseacro,paynwde2retope3rwfeoermkesdporinor to terminationof the study. urinalysis were collected Blood and urine from 15 animals samples for hemotology, per sex per dose group at clinical chemistry, and 3, 6, 12, 18, and 24 months. Termination schedule: An interim control and high dose groups. termination at 1 year involved 15 animals per sex from the Organs examined at necropsy: Organ weight: Adrenal glands, brain, heart, kidney, liver, uterus and testes for 15 animals per sex per group. Macroscopic examination: thorax, and cranium. External surfaceofbody, all orifices, and contentsofabdomen, hMiigchrodsocsoepigrcoeupxsa:minadarteinoanl:, Taohretaf,oblrlaoiwni,negyeosr,gahneasrwt,ersemaelxlaimnitensetdinfe,orlaarngiemailntsesftrinoem,tkhiednceonyt,rolilvearn,d slpuinnga,llcyomrpdh/bnoondeem(amrerseonwte(rviecr)t,ebmraa)m,msaprlyeeng,lasntdo,moavcahr,ietsh,ypraonicdrepaasr,atphiyturiotiadr/yt,rsaaclhievaa/reysgolpahnadg,us, atensytigsr/oespsidlieysmioind.es,Alulrionfartyheblaabdodveer,tiustseureusswoerrperoesxtaatmei,naendyfiosrsauneimmaalsssienst(hseuslpoewctaenddtmuimdodrsl)e,daonsde groups except: marrow. aorta, brain, eyes, small and large intestines, lymph nodes), and spinal cord/bone Additional Endpoints: `Mmeotnatbhoslainsdm seaxmapmliensaotfiloinv:eOrv,ekmiidgnehyt,usrpilneeena,ndlunfegc,aalnsdambpolneesmwaerrreocwolwleercetetdaakten2,f5r,o1m1,$ aanndim2a3ls per the sex per group at the 1 and 2 year scheduled presence ofN-EtFOSE alcohol and POS. sacrifices for total organic fluoride analysis for RESULTS bNeOnAotEeLd t(hNatOiEnLc)i:denTcheoefinovveasrtiiaganttourbsucloanrshiydpeerrepdlaasdioasweaosfs3i0gnpifpimcanttolbyeinthcereNasOeAdEfLor.allIttsrheaotueldd `groups and apparently dose-related. LefOfeActEs,Lin(cLluOdEiLn)g:hyTpehretrionvpehsytiagnadtovrascucoolnastiidoenr.edAg1a0i0np,pitmsthooubledtbhee nLoOteAdEtLhabtaisnecdidoenncleivoerf ovarian tubular hyperplasia was significantly increased for all treated groups and apparently rat niasess Report Appeic var 000280 dose-related. Remarks: Bfoordtyhewefiigstht6:wBeoedkysowfeitghhetsgtauidnysawnedrethdiseplroewsesredboidnythweeitrgehatte(dapmparloexsimwahteenlyco1m4p%ardeecdrteoasceonftorrols hstiugdhy.dosTheiasnedff2ectto w6a%sdaelcsroeoabsseefrovredloiwn atrnedatmeiddf-edmoaslee)s,waasltmhaoiungthatihneedonfsoerttwhaesdusrlaotwieornoafndthtehe difference from Tow dose at the controls wes greater endofthe study). (21% decrease for high dose, 15% for mid, and 3.5% for gFeonoedr/awllayteirnccroenassuedmpitnitornea:teDdaialnyimfaelesd,cgornasduuamlpltyioinncpreeraskiinlgowghreamnmceoamnpabroeddytwoeciognhttrowlagsroup feed intake. the last This effect was 10 study weeks pronounce in treated males and less consistent for treated females unil cToesntsuMamteedribaylaCnoinmsalusmpotnioanm:g/Tkhge/dfaoyllboawsiins:g table summarizes the amountoftest material TeTre Target Dore Achieved Dose Levels - Mean (mg/kg/day) [ ow mw ee ] Colcicnuircraeldsiatgnsslig(hdtelsycreilpetviaont,edsreavteersitiyn, htiigmhedoofsoensmeatleasn,dwdeurreattihoen)o:nlCylocnliinciccaolnsviuglnsioocncsu,rwrihnigcmhore sfiraeqluoednatclryyoiandterneiattsedviarnailmailnsf.ectTiohne, twrietahtecdlipnoipcuallastiigonnseixnpcelruideinncgesdwoalsluesnpescutbemdanoduitbbruelaakrosfalivary `rgelsaonldvseadnwditohcicnas1i0ondaalyoscaunladrtmhaeniinfecsitdaetnicoenosf,rbeseitdwueaeln otchuelafirrscthaanndgessccwoansd emxotnrtehm.elTyhleosww.elTlhieng control population had comparable signs during Month 16. tHheemdaitfofleoregnyc:eRferdomblcoonotdrocellslwcaosunsttsatwisetriecaldleycrsiegansiefdiciannthiagth6,do1s2e, afnedma1l8esmotnhtrhosu.ghoMuotrpthheolsotguidyc;al cofhacnhgaensgeinrweasdbgleonoerdalcleyllnsowteerdeasobssliegrhtv.edHienmhaitgoheraintdvmaildu-esdofsoer fheimgahldeossaetf2e4mamloensthwse;rethe degree dsiegcnriefaisceandtilny hdiegchredaosseed fatemtahleeMsofnrtohm 3Moenvatlhua3titoonMaonndthhe2m4o.glSolbigihntvdailfufeesrewnecrese isnigwnhiifticeabnltloyod cell parameters were not considered treatment-related or biologically meaningful. aCmliinnoitcraalnCshfeemraisset,rya:lkAatliMneonphtohsp3h,astlaisghet, ianncdrebalsoeosdinuraelaanniinteroagmeinnowterraensofbesrearsev,edasipnatrrteaatteed males. Hamiignhotdroasnesf(earnadsoecacnadsiaosnpaalrltyatmeida-midnooster)amnsafleersahseadfrmoomreMopnrtonho6unucnteidl itnhcerseatsuedsy icnonacllaunsiinoen. [Er r-------- vas 000281 Ophthalmologicfindings: No treatmentrelated effect. Mortality and time to death: The following table summarizes the survival data: a= EYEN [om we [e we]| om] on wn] Gross pathology incidence and severity: At the Year 1 sacrifice, high dose males had an increased incidenceofpale and/or tan livers (other dose groups were not examined). Other organs from treated animals were not notably different from controls. For scheduledstudy termination sacrifices and unscheduled deathsofanimals in the `high dose group, gross findings were primarily limited to the liver, including a increased incidence.of hepatic masses, nodules and raised lesions, mottled livers, and yellow or `pale focal lesions. were observed for animals in the low and mid-dose groups. No treatment-related effects Organ weight changes: Year | Sacrifice: Animals in the high dose group had statistically significant increased absolute and relative liver `weights and significantly decreased absolute `heart and spleen weights. Relative kidney and brain weightswerealso observed to be significantly increased in these animals. High dose males also had significantly lower adrenal (absolute) and pituitary (absolute and relative) weights and significantly increased relative testicular weights. High dose females had significantly increased relative uterine and adrenal weights. Endof Study: Only high dose animals had statistically significant increased absolute liver weights; high and mid-dose animals had significantly higher relative liver weights. Relative kidney weights were significantly increased in high dose animals. Absolutespleen weights were significantly decreased in both high and mid-dose males; however, only high dose males had significant decreases in relative spleen weights. examined. Histopathology: Year | Sacrifice: Hepatocellular hypertrophy and vacuolation was common for animals in the high dose group and hepatocellular necrosis was found in 6 of 15 high dose males Endof Study: `animals in the Hepatocellular `hypertrophy high dose group and found and vacuolation were consistently observed at lower incidence rates in the male low and for mid-dose groups. Incidenceof hepatocellular cystoid degeneration appeared to be associated with dose in `males, while this affect was observed only in high dose females. The incidence of nodular hyperplaofstihae adrenal c statistically significant and ortex dose was. significantly increased in the high dose dependent increase in tubular hyperplasia of males. There was the ovarian stroma a of females (0/50 in controls; 13/50 at 10 ppm; 23/50 at 30 ppm; 31/50 at 100 ppm; p<0.001 for Pr v0e 00282 all doses by Fisher's exact test). The incidence of nodular `hyperplasiaofthe adrenal cortexwas. significantly increased in high dose males. A statistically significant increased incidence of foamy macrophage neoplastic changes accumulation in the were not considered lung of high dose treatment-related. animals was observed. Other non- Sporadic incidencesof various neoplasms were noted, including pituitary adenomas and mammary gland adenocarcinomas; however, these did not appear to have a relationship to dose. Hepatocellular carcinomas and adenomas were observed with the following incidences: incidence of Hepatocellular Carcinomas and Adenormas No.of Animals Affected (%) Joe [imme 1 aww | oom | weeenn || oTchcueriinncainynocneeofacnairmcail)norn ad adenoma id nt ovrep (both nels id nor statistical significance. `The investigators noted that while the incidenceof hepatocellular adenomas and carcinomas in high dose females was outsideofhistorical control limits, the difference did not achieve Additional Endpoints: Metabolism examination: Results not provided (analysis performed by Sponsor) CONCLUSIONS The most pronounced treatment-related effects were seen more frequently in high dose animals than in controls. A in the liver statistically and occurredsignificantly significant increased incidence of foamy macrophage accumulation in the lung ofhigh dose animals was observed and thought to be possibly related to treatment. In addition, there dose-dependent increase in tubular hyperplasiaof the ovarian was a. statistically stromaoffemales significant and rats. Based on tumor incidence, types of tumors, onset time of tumor appearance, malignancy patternsoftumors and the final mortality values at 2 years, the investigators concluded that not carcinogenic in the rat under the design and conditionsofthe study. N-EtFOSE alcohol was DraftInitialAssessment Report - Appendix V0 000283- REFERENCE RSiTkUerDLYabOorFatForLieUs,OIRncO.CH19E8M9.ICTAWLOFYM-E3A9R24OIRNARLAT(SD.IET()RTIOKXEIRCEIxTpeYriCmAeRntCINoN.OGENICITY 0281CROO12) -------- var a) 000284 ROBUST SUMMARY - RS34 `Title: 4-Week Capsule Toxicity (PFOS; T-6295) in Cynomolgus Study with Perfluoroctane Sulfonic Monkeys. Unaudited Draft. 1995. Acid Potassium Salt TEST SUBSTANCE Identity: Potassium Perfluorooctylsulfonate, CAS No. 2795-39-3 Remarks: PFOS; T-6295 METHOD Method/guideline followed: Range finding ~ Unaudited Draft report, sections missing Study duration: 28 days GLP (Y/N): Y, sections missing report contains GLP statement, but as submitted, unaudited draft report with Yearstudyperformed: 1998 Species/Strain: Monkey/Cynomolgus Sex: both Number of animals per dose: per sex, 2.0 mg/kg/day 2 per sex, 0 mg/kg/day: 3 per sex, 0.02 mg/kg/day; Routeofadministration: Capsule in stomach Doses tested and frequency: 0 mg/kg/day; 0.02 mg/kg/day; 2.0 mg/kg/day Post-observation period: none Statistical methods used: none wReermearrekcso:rdTedhetwmiocnekweeyesklwye.reHeombasteorlvoegdiactalleaasntddcaliilnyicfaolr cgheenmeirsatlrcylianniaclaylsseisgnwseraendcobnodduyctweedigohnts samples collected before the beginning of the study at day -7 (baseline values) and collected on study days 2, 7, day and 29. 14. Additional blood samples Blood samples for serum for clinical chemistry were PFOS concentrations were taken odnayda-y7sa-n7d,2d,a3y,279, w1e4,reanadna2l9.yzeIdn afodrdilteivoenl,ssoafmpesltersadfirolo,mestrone, estriol, thyroid stimulating hormone, days. At triiodothyronine, and necropsy a sample of thyroxin. liver was The study animals were terminatedas scheduled at 30 collected from each animal for palmitoyl CoA oxidase \ ref nia ssssnens Report- Append var . 00028% activity analyses. Samples of liver, testes, and pancreas were collected for proliferation cell nuclear antigen evaluation. A sampleofliver was also collected from each animal for PFOS concentration analysis. The following organs from control and all treated groups were examined microscopically: adrenals, eye, kidney, liver, lung, spleen, pancreas, femoral bone marrow, testes, and thymus. RESULTS NOEL (dose and effect): 0.02 mg/kg/day LOAEL (dose and effect): 2.0 mg/kg/day. Dramatic reduction in serum cholesterol both male and female `Toxic response/effects by dose level: Only high-dose effect, 2.0 mg/kg/day. Dramatic reduction in serum cholesterol both male and female Statistical results: None, high-dose too few animals (1 male, 1 female) CONCLUSIONS Dramatic reduction in serum cholesterol in the high dose animals. Estradiol andtriiodothyronine levels were lower in the high dose animals at the endofthe study. Since the numbersoftested `animals are small (one male and one female in the high-dose group) and baseline levels are variable, it is not clearifthese hormone level changes are treatment-related. Remarks: Draft report does not discuss drop in serum cholesterol REFERENCE "Thomford, P.J. 1998. 4-Week Capsule Toxicity Study with Perfluoroctane Sulfonic Acid Potassium Salt (PFOS; T-6295) in Cynomolgus Monkeys. Unaudited Draft. for 3M, St. Paul, MN, by Covance Laboratories Inc., Madison, WI. Study No.T-6295.6, OTHER `Summary revised 8/11/00 Ot etsmepu.pent 6v 00286 . ROBUST SUMMARY - RS35 Title: First ninety-day rhesus monkey toxicity study, 1979 TEST SUBSTANCE Identity: Potassium perfluorooctylsulfonate, CAS # 2795-39-3 Remarks: FC-95 METHOD Method/guideline followed: None Study duration: 90 days GLP (Y/N): No Year study performed: 1978 Species/strain: Rhesus monkey Sex: Males and females Numberof animals per dose group: 2/sex/group Route of administration: Gavage Doses tested and frequency: 0, 10, 30, 100, 300 mg/kg/day Post-observation period: None Statistical methods used: None sRteumdayriknsit:iatDiiosntialnldedthweatfeermawlaessuwseeidghfoerdt2h.e7v5e-h4i.c1l0ekcgo.ntrTohle. mTohnekmeaylsewsewreeiogbhseedr3v.e0d5d-a3i.l8y0fkogr at cgheenemriasltrcyliannicaallysseisgnasnadnudribnoadlyyswiseiwgehrtescwoenrdeucrteecdoradtetdhweebeekglyi.nniHnegmoaftotlhoegsitcuadly.anTdhcelisntiucdaly was tspelremeinn,atpeitduaitfatreyr,2k0iddnaeyyss,duteesttoest/hoevadreiaetshaonfdbtrheaimnonwkeeryes.weiAgthende.crTophseytthhyerohieadr/tp,arlaivtehry,roadirdewnearles:, wpereisgehrevdedafitnerRufsisxaetlilo'n.s fiTxiastsiuvee.s wTehreefporlelsoewrivnegdoirngabunfsfferreodmnceountrraoll 1a0nd%aflolrtmraelaitne;d tghreouepyseswweerree ecoxraomnianreydvmesiscerloss)c,opdiucoadlelny:uma,dreinlaelusm,, jaoerjtuan,ubmr,aicne,ceusmo,phcaogluosn,, reyeecst,umg,alklibdlnaedydser,,lihveearr,tl(uwnigt,hskin, mspelseeennt,erpiacnclryeamsp,hpnroosdtea,ter/euttreorpuhsa,rbyonngee/albolnyemmpahrnroodwe,(mrbamjumnactriyon)g,lasnadl,ivnaerryvegl(awnidt,hlmuumsbcalre)s,pinal Dre ii sessment Report Apps vou000287 : cord, pituitary, stomach, testes/ovaries, thyroid, parathyroid, thymus, traches, tonsil, tongue, urinary bladder and vagina. RESULTS NOAEL (dose and effect): None LOAEL (dose and effect): None Toxic responseleffects by dose level: Allofthe monkeys in the treated groups died. Statistical results: None R10e0mamrgk/skg:/dTahyegmroonukpedyisedinbetthewe3e0n0dmagy/sk3g-/5d,atyhegrmoounpkdeiyesd binetthweee3n0dmagy/skg2-/4d,atyhgermoounpkdeiyesd in the btreetawtemeenntd.ayTshe7-m1o0,nkaenydsthfermoomnaklletyhseignrotuheps10shmogw/ekdg/sdiamyilgarrosuipgndsioefdtboextiwcieteynidnacylsud1i1ng-20 of decreased twitching, awcetaivkinteys,se,mecsoinsvuwlistihonssoamneddpiraorsrthreaat,iobn.odyAtstnieffcernoipnsgy,,gesneveerraallboofdtyhetrmeomnblkienygs, in the e1x0a0mainndat3i0o0n msgh/okwge/ddanyo gmircoruopsschoapdicalyeesilolnos.wisCho-nbgreoswtniodni,schoelmoroartrihoanogefatnhed lliivpeird;dheipslteotlioogniocf the adrenal cortex was noted in al treated groups. No other lesions were noted. CONCLUSIONS Remarks: Authors conclusions stated above in results. Reviewer agrees. REFERENCE Goldenthal, EL, D.C. Jessup, R.G. Geil and 1.5. Mehring. 1979. Ninety-day subacute rhesus monkey toxicity study. Study No. 137-087, Intemational Research and Development Corporation, Mattawan, ML OTHER PT ------ vas . 000288 ROBUST SUMMARY - RS36 Title: Second ninety-day rhesus monkey toxicity study, 1978 TEST SUBSTANCE Identity: Potassium perfluorooctylsulfonate, CAS # 2795-39-3 Remarks: FC-95 METHOD Method/guideline followed: None Study duration: 90 days GLP (Y/N): No Year study performed: 1978 Species/strain: Rhesus monkey Sex: Males and females Number of animals per dose group: 2/sex/group Route of administration: Gavage Doses tested and frequency: 0,0.5, 1.5, 4.5 mgkg/day Post-observation period: None `wSetrateisctoicmaplamreetdhboydsanuaslyesdi:s oBfovdayriwainsc,eh(eomnaet-owlaogyicclaals,sibfiiocacthieomni),caBlaratlnedttu'rsintaelstysainsdatnhdeorgan wis appropriate t-test using Dunnett's multiple comparison tables to judge significance of differences. Rsteumdayrkinsi:tiatDiiosntialnldedtwhaetfeermawlaessuwseeidghfoerdt2h.e7v-e3h.i7c5lkeg.conTtrhole.moTnhkeemyaslweesrweeoibgsheerdve2d.5d5a-i3l.y55fokrg at `cgheenmeirasltrcylianincaallysseisgnasnadnudribnoadlyyswiseiwgehrtes cwoenrdeucrteecdoradtedthweebeekgliyn.niHnegmoafttohleogsitcuadly and and clinical after 30 and 9te0stdeasylsoovfartireesaatmnednbtr.aiAntwenreecrwoepisgyhtehde. hTeahret, tlhiyvrero,ida/dpraernaatlhs,yrsopildeewne,rpeiwtueiitagrhye,dkiadftneerysf,ixation. Tfiixsastuievse.weTrheepfroelsleorwviendgionrbguafnfserferdomnecuotnrtarlol10an%dfaolrlmtarleiant;edthgereoyuepss wweerree perxeasmeirnveedd in Russell's microscopically: adrenals, aorta, brain, esophagus, eyes, gallbladder, heart (with coronary ef na ssssmen Report Append "000289 vessels), duodenum, ileum, jejunum, cecum, colon, rectum, kidneys, liver, lung, skin, mesenteric Iymph node, retropharyngeal lymph node, mammary gland, nerve (with muscle), spleen, pancreas, pituitary, sptroosmtaacthe,/utteesrtuess,/obvoanreie/sb,otnheymroairdr, opwar(artihbyjruonicdt,iotnh)y,musasl,ivtarraychgelaa,ntdo,nsliul,mbtaorng`usepi,nuarlicnoarrdy, `bladder and vagina. RESULTS NOAEL (dose and effect): None (Reviewer disagrees, see remarks) LOAEL (dose and effect): 0.5 mg/kg/day (Reviewer disagrees, see remarks) "Toxic response/effects reported by dose level: 4.5 mg/kg/day - 4/4 monkeys died between: `weeks 5-7, clinical signs (anorexia, emesis, black stool, dehydration), significant the adrenals, moderate diffuse reduction atrophy of in serum cholesterol, marked diffuse lipid depletion pancreatic acinar cells, moderate diffuse atrophy of in serous alveolar cells. 1.5 mg/gk/day ~ clinical signs (soft stools, diarrhea), reduced alkaline phosphatase activity and serum potassium (females), body weight, reduced serum reduced serum cholesterol (1/2 females), reduced inorganic phosphate (1/2 females). 0.5 mg/kg/day -- clinical signs, (soft stools, diarrhea), slight reduction in serum alkaline phosphatase `Statistical results: Statistical results are generally reported as a comparison to the controls, and males and females are treated separately. With caught rhesus monkeys, this the small numbers (2/sex/group) and the fact that type of comparison may not be as appropriate for these were:wild- manyofthe endpoints as acomparisonofthe actual change in individual values for various parameters from pre-study individual values. A case in point is the analysis of alkaline phosphatase, as discussed at length below. Remarks: All monkeys in the 4.5 mg/kg/day group died or were sacrificed in extremis between week $ and 7ofthe study. Beginning on the first or second day of the study, these monkeys exhibited signs ofgastrointestinal tract toxicity including anorexia, emesis, black stool and dehydration. All of the monkeys convulsions, had decreased activity and just prior to death generalized body trembling and prostration. showed marked to severe rigidity, The mean body weight decreased from 3.44 kg at the beginningof the study to 2.7 kg at week 5. After 30 daysoftreatment, there was a sacitginviiftiyc.anAttrendeuccrtoiposny,inmseearnumorcghaonlewsetiergohltsanwderae5c0o%mpraerdaubclteioanmionnsgertuhem caolnktarloilneapnhdotsrpehaatteadse monkeys. Histologic examination showed several treatment related lesions. All the male and f`meomdaelreastehaddifmfausrekeatdrodipfhfyuosfetlhiepidpadnecprleeattiiocn eixnotchreinaedrceenlallss.witOhndeemcraelaeseadndcetllwosifzeemaanldeslohsasdof ot ret 000290 Zalyvmeoolgaernceglrlasnuclheasr.actTewriozemdalbeysdaencdreoanseedfceemlallseizheadanmdodleosrsatoef cdyiftfoupsleasamtircopghryaonfuletsh.e serous Awlelemkoonfktehyesstiundtyh,eth1e.5mmogn/kkegy/sdahyadgrdoeucpresausrevdivaecdtiuvnittiyl. thSeigennsdoofftghasetrsotiundtye.stiDnuarlitnrgactthteoxfiircsitty wanedreblnoooteddy osctcooals;ioantatlhleyednudroifngtthheesstutduyd,yaannodreixnical,uddeedhybdlraactkiostnooolr,gdeinaerrrahleab,omduyctoruesmbilninthgewsetroeol ndortoepdp.edAlftrhoomu3g.h15staktgisattictahlesbigengiifnincianngceofwatshensottuadcyhtioev2e.d9,3tkhge matetahne beonddoyfwetiheghsttuodfy,thaenmdatlhees `thmeeafnebmaoldeyswheaidghatosifgntihfiecfaentmarleedsucdtrioopnpiendsferroumm3a.l2k2aklignteoph2o7sp5hakte.aseAfatcetriv9i0tydaanyds osferturmeatment, paontdaasnsoituhmerlehvaeldsawreerdeucntoitoendiinnitnhoergreapnoirct.phOosnpehaotfet.hNeefcermoaplseys hraevdevaleerdy nloowtrseeartummencthroelleastteedrol lesions. All monkeys in gastrointestinal the 0.5 mg/kg/day tract oxicity were group noted oscucravsiivoendalulnytidlutrhienegntdhoef stthuedysatunddy.incSliugdnesdodfiarrhea, soft S`tAooelrs,9a0nodraeyxsioafantrdeaetmmeesnits,. aOsclciagshitodneaclrleya,sdeeicnresaesreudmaacltkivailtiynewpahsonsopthaetdaisnetwhareseonfottehdeimnotnhkeeys. report. Necropsy revealed no treatment related lesions. "STihgenisftiucdayncreepaoprptesasrisgtnoifbiecaantcdoemcpraeraisseosnoinfalmkaalleinaenpdhofsepmhaalteagsreoiunpalmleoasnsewgirtohupcso.ntrTolhse. teDstueforto tchoempsamralilsonnumobfeirnsdiovfidaunailmvaallsuaesndobwtiadienepdotaefnttriasltvuadryiaitniitoinatiinowniwlidt-hcapurgeh-tstruhdeysuvsalmuoenskweoyusl,daseem mExoarmeianpaptrioopnroiaftteh.eTihneditvaibdluealbevlaolwuepsraesnednttshealmlatghneitinuddieviodfuaclhadnagtae fionrtahleksaelivnaelupehsosfprhoamtatshee.preSotcucduyrrteodtihnettheerm0.v5amluge/kwgitahnidn t0h.e15comngt/roklgadnodsdeodsgerdougprso.uAps sruegpgoersttesd tshiagtninfoicsaingtn"ifdieccarnetasceh"anignes allekvaellianse aphLoOsEpLh.ataTsheeinretphoert0.t5abmlge/s kagctduoalsleydsghroowupa issitghneifpircianmtardyifbfaesriesncfeorartetprhpeese<nt0i.n0g5tlhiesvedlofsoer a{lhkeasltianteispthicoaslpchoamtpaasreiisnotnheagmaailnesst,tahendcotnhtirsolis; thaokweenvaesra, idnecrreeaalsiety., tTihsisclmeaarylybeinceorrrroerc,tsbiansceedbootnh mvaallueessajcutsutalhlayppsehnoewdedtoabpeprcooxnismiadteerlaybl1y0l%oweirnctrheaansetsheiinr atlwkoalminaelephcoosnpthraotlacsoel.lTehaeguiersp.reB-assteuddyon his analysis, it would appear that a NOAEL for the study does exist, and that this NOAEL is 0.5 mgke. Dr niilAssessReport pedi v1000291 Table. Individual and group mean alkaline phosphatasevalues. Tndividual and Mean Alkaline `Phosphatase (IU/L) by Time Period `Absolute | Change, | Percent. | Change, and Dose Group Dose Animal Pre-Study | Pre-Study Through | Through Group Term Term CMoonmkeoys M[T de [m0 |T G0] 671] Pre-Study | 1 Month 3 Months FFs [Tmo [iiss [5% | _ea| 2513] SDomseog[Me[aMan7AS [r [e72s5 [[9sm% a [[[6os3oe| ||__s -A7s5oe5|] tfoa6so6o]]l GMroonukpeys [Ven [s [sw i | 4s 2 er] DGTorSsomewoke[[MF77458060 [11[ 02800 {Tss o [o6 | t | 380e 04|] 2336.0114]] MToinknegyss[[[FVM7e701[[f4[ o96u0s Dfo[ ns o [7se | | s d8r s6]] 1db8ee7so0s)]] DGorsoew [[FM7assosr [[9t6osts Monkeys [F7soy [7a [[[ ssiees | || r4o0a1]] d4o1a5r5]] [o[ es | Atl isis] [ew [10s [So |= | 4ss| 877] `CONCLUSIONS As reported, noted in the the 0.5 study mg/kg does dose not have group (t a 'NOAEL, s he low dose). ince In areduction in actuality, this alkaline reviewer phosphatase believes that is a NOAEL of 0.5 was obtained in the study as aresultofinappropriate analysis of alkaline `phosphatase values. REFERENCE Goldenthal, EL, `monkey toxicity D.C. study. Jessup, Study NRo..G.1G3e7i-l09a2n,dIJn.tSe.mMaetihornianlg.Re1s9c7a8.rcNhiannedtyD-edvaeylsoupbmaecnutte rhesus Corporation, Mattawan, MI. " ---- -- ROBUST SUMMARY - RS37 Title: Ninety day study in rats, 1978 TEST SUBSTANCE Identity: Potassium perfluorooctylsulfonate, CAS # 2795-39-3 Remarks: FC-95 METHOD Method/guideline followed: None Study duration: 90 days GLP (YIN): No Year study performed: 1978 Species/strain: Charles River CD (Sprague-Dawley) rat Sex: Males and females Number of animals per dose group: S/sex/group Route of administration: Dict Doses tested and frequency: 0, 30, 100, 300, 1000, 3000 ppm Equivalent to 0, 2, 6, 18, 60, 200 mg/kg/day Post-observation period: None Swtearteisctoicmaplamreetdhboydsanuasleysdi:soBfodvayriwainsc,eh(eomnaet-owloagyicclaals,sibfiicoacthieomn)i,caBlaratlnedttu'rsintaesltysainsdatnhdeorgan wis appropriate t-test using Dunnett's multiple comparison tables tojudge significance of differences. RTehmearankism:alTswheermealoebssewreviegdhedadil1y96fo-r23ge2ngeraanldcltihneicfaelmsailgensswaenidghbeoddy1w6e5i-g2h0t6sgwaetrsetruedcyoirndietdiation. wbeeegkilnyn.ingHoefmatthoelosgtiucdyalanadndafctleirni3c0alacnhdem9i0sdtaryysanoafltyrseeastmaenntd.urAintalnyescirsowpesryethceo,nldiuvecrt,eaddratentahles, sfipxlaeteino,n.pitTuiistsaurye,skwiedrneeypsr,easenrdvberdaiinnbwuefrfeerweedignehuetdr.alT1h0e%thfyorromiadl/ipna;ratthheyeryoeisd wweerree pwreeisgehrevdedafitner R`muiscsreolslc'ospifciaxlaltyi:ve.adrTehnealfso,laloorwtian,gbroarigna,n,sefyerso,m ,choenatrrtol(waintdh aclolrtorneaatreydvgerssoeulpss),wdeuroedeexnaummi,neildeum, Dv nit AssRepeort nAppetdic "000293 j`geljaunnd,umn,ercveecuspml,eecno,lopna,ncrreecatsu,m,prkoisdtnateey/su,telriuvser,,blounneg,/bsoknine,mmaersernotwer(isctelmyummp)h, nsoadleiv,ar, ymaglmamnda,ry lumbar spinal cord, pituitary, stomach, testes/ovaries, thyroid, parathyroid, thymus, and urinary bladder. RESULTS NOAEL (dose and effect): None LOAEL (dose and effect): 30 ppm (2 mg/kg/day) Toxic responseleffects by dose level: 3000 ppm -- 10/10 rats died between days 7-8. 1000 ppm 300 ppm -- -- 10/10 rats died between days 8-14. 5/5 male rats died between days 13-25; 5/5 female rats died between days 18-28. "sAec1o3n0d,ar1y0(0s0plaenedn,30me0s0enptpemri--c hliysmtpolhogniocdelses)ilonysmpinhotihed porrigamnasr,y s(ttohmyamcuhs,, ibnotnesetimnaesr,romwu)scalnedand skin. 100 ppm -- 2/5 males and 2/5 females died during week S and a third male died during week 11, `fmoeoadncboondsyumwpetiigohntssiwgenrifeicraendtulcyerdedbuyce1d6,.s7i%gn(imfailceasn)t raendduc1t6i.o3n%in(fheemmaalteosc)riatt (smtauldeyst)e,remriyntahtrioonc,yte s(imganliefsi)c,anhtemioncgrleoabseinin(maablseolsu&te f(efmeamlaelse)s,)laenudkorceyltaeti(vmea(lmeasl)e,sa&nd freemtailceulso)cylitveer(fweemiaglhets)ancodunretlsa,tive Kidney weight. A100, 300, 1000 and 3000 ppm -- slight to marked focal necrosis of hepatocytes. (3f0empaplmes--) aSingdnirfeilactainvterleidvuecrtwieoingihntf(omoadlecsonasnudmpfetmiaolnes()m.ales), significant increase in absolute `Atall dose levels -- very slight to slight cytoplasmic hypertrophy of hepatocytes in the Scteanttirsitliocbaullarresruoltmsi:dzo1n00alprpemgi--onssi,gneisfpieccainatllryediuncmtailoens.in food consumption Remarks: days 13-25 Allofthe and days 1r8a-t2s8infotrheth3e00m,al1e0s0a0nadndfe3m0al0e0s,ppremspgerctoiuvpeslyd,ieidn. Death the 300 occurred between ppm group. At of100tr0eaptpmmen,t.deaTthheocractusrriendalblebtuwtetehnedlaoywses8t-1d4o,seangdroatup30s0h0owpepdm,sitghnesorfattsoxdiiceditbyetiwnceleundidnagys 7-8 emmaatceriiaatlioanr,ocuonndvtuhlesiaonnosgefnoiltlaolwrienggiohna,ndilnicnrge,asheudncsehnesditbiavictky, troedexmtaetrenrailasltiamruoluin,drethdeuceeydesa,ctyievliltoyw and moist red material around the mouth or nose. `Tmharleees maanldetsheantdwotwfoemfaelmeasledsieidndtuhrein1g00wpeepkm5graonudptdhieetdhiprrdiomra1l0esdciheeddudluerdinsgacwriefeicke.11oTfwtohoefthe astnuddyf.emAatlestgurdoyuptse,rmrienspaetcitoinv,elmye.anAvbeordaygewefiogohdtscownesruemrpetdiuocneddubryin1g6t.h7e%enatnidre1s6t.u3d%y pienrtihoedmale t(@r/eraattmiednaty,)hweamsatsoilgonigfiiccavnatlluyersewdeurceedcofomrpamraalbelseaandmofnegmatlheescaotnt1r0o0lpapnmd. 10A0ftperpm30grdoauypsso.fClinical cuhreeaminsittrryogaennalvyasleusesationnmealmeosnatnhdsfheomwaeleds,a asingdnicfriecaatnitniinnecrpehaossepihnomkienaanseglauncdosaelkianlimnaeles, blood phosphatase values for females. After 90 daysof treatment at 100 ppm, the two surviving males, rap nia sss Report Append V vor 000204 shuardvisivginnigfifceamnatllyesrehdaudcseidgneirfyitcharnotclyytre,edhuecmeodglhoebmiong,lohbemiantaocnrdirteatincdulloecuyktoeccyotuenctosu,natss;wetlhle atshree sSlhioghwteldy lsloiwgehrt teorymtohdroecryattee, ihnecmraetaoscersitinapnldalsemuakogclyutteamciocunotxs.alaTcewtoicoafntdhepysruurvviicvitnrganfseammailneasse dacatyisv.itieRse.latUirvienalliyvseirswreeisguhlttswwaesresicgnoimfpiacranatbllyeiancmroenasgedtrienattehde amnadlecsonatnrodlagbrsoouluptseaat n3d0 raenladti9v0e liver weights were significantly increased in the females. Relative kidney weights were significantly increased in both sexes. bAoldyratwseiinghtthse w3e0rpeprmedgurcoeudpbsyur8v.i7vaenddun8t%il itnhetheenmdoafltesheansdtufdeym.alAets,srteusdpyectteirvmeliyn.atiAovn,ermaegaenfood c3o0npspumm.ptiHoenmadtuorlionggitchevaelnutiersewsetruedycopemrpiaordab(gl/eraatmidoanyg) wtahescsoingtnrioflicaanndtly30repdpumcegdrfoourptahte 3m0alaensdat i9n0cdraeyass.edOanlkealfienmeaplheossphhoawteadsaesllievgehltalty3e0ledvaaytse.d gAltu9co0sdealyesv,elonaendmaolnee smhaolweesdhmoowdeedraates.lightly hinacdresaisgensifiincagnltucionscere,absleosoidn uarbesaolnuitteroagnednraenldatyiv-eglluitvearmywleitgrhatnss.peTphtiedamsaeleacstihvaidty.sigTnhieficfaenmtales decreases in absolute and absolute pituitary weight. relative adrenal The biological swiegingihftisc,anacbesoolfuttehethcyhraonigde/spairnatmhaylreoiodrgwaenigwhetigahntds is unclear since similar changes were not noted in higher dose groups. VAatrnyeicnrgodpesgyr,etersoeaftmdeinstcorleolraatteidognroasnsd/loersieonnlsarwgeermeepnrtesofetnhteinlialvlertraenadteddigscrooluoprsatainodn oifnctlhueded g`grloaunpdsu.larCemnutcriolsoaboufltarhetosmtiodmzaocnha.l Hciysttooplloagsimciecxhaympienrattrioopnhyaolsfohsehpoawtoeedytleessiaonnsdifnoaclallrneeactreosdis wadadsitoibosn,erevsepdeciinaltlhye alimvoern;gthreatisnicnidtehnec3e0a0,nd1r0e0l0atainveds3e0v0er0itpypwmergerogurpesa,tetrreianttmheentmarleelsa.tedIn `himsetsoelnotgeircicllesyimopnshwneordeesn)otleydmpihnotihde porrgiamnasr,ys(ttohmyamcuhs,,ibnotensetimnaesr,rmouws)calnedasnedcsoknidna.ryIn(stphleeetnh,ymus, `thmiasrcroonwsihsytpeodcoelflduelparliettyiownasinntohteedn.umTbheersapnldeesnizweaosftslhieghltylympahtoroipdhifeoldlwiciltehs aancdorirnetshpeobnodnineg dinectrheeasmeesiennttheeriscizleyamnpdhnnuodmebse.r Mofucloysmaplhohiydpefroklelricalteossiasndancde/llosraancdanathsoismiislawradsepolbesteirovnewdaisn ntoheted fDoercersetaosmeaacthroapnhdymiunctohsealhehieghmtorarnhdatgheisckwneersesonfottehde ivniltlihewgelraendnuoltaerdpionrtthieonsomfatllheinstetsotmianec.h. Atrophyof the skeletal muscle was noted, as well as epidermal hyperkeratosis and/or acanthosis `was noted in the skin. CONCLUSIONS Remarks: Authors conclusions stated above in results. Reviewer agrees. REFERENCE Goldenthal, EL, D.C. Jessup, R.G. Geil and J.5. Mehring. 1978. Ninety-day subacute rat toxicity study. Study No. 137-085, International Research and Development Corporation, Mattawan, M1. OTHER rat itlsess Report Appi . "000295 - ROBUST SUMMARY - RS38 Title: 13-Week Dietary Toxicity Study with N-Methy! Perflurooctanesulfonamido Ethanol (NMFOSE) in Rats. TEST SUBSTANCE Identity: N-Methy! Perflurooctanesulfonamido Ethanol (N-MeFOSE) Remarks: METHOD Method/guideline: None Test type: 14 week dietary toxicity study GLP: Yes Year: Not specified (Study start date: August 27, 1998) Species: Rat Strain: Crl:CD'(SD)IGS BR Route of administration: Oral (in chow) Doses/concentration levels: 0, 3, 30, 100 ppm N-McFOSE Sex: Male & Female Exposure period: 14 weeks Frequencyoftreatment: ad libitum Control group and treatment: Concurrent vehicle Post exposure observation period: Not specified Duration of test: 14 weeks (Stpa<t0i.s0t5i)ca,ltmreatnshfoodrsm:atLieovnisnew'esretesutsefdortvoasrtiaabnicleizheotmhoegveanreiiantcye;. inCocamspeaorfishoetnetreosgtesntcoiotkyovfarviaarnicaence ahentaelryozgeednebiotdyyiwnteoigchotnssiadenrdatbioodny. wOenieg-hwtacyhaanngaleyss,ifsooofdvcaornisauncmept(iAoNn,OVoArg)a,nifweaipgphltisc,abalned: gcornotuipncuoomupsapriastohnosl.ogGyrvoaulupesc.om1pfasriigsniofniscawnet,reDuenvnaeltuta'tsedteastt tpheerf5o.r0m%e,dtwfoor-tcaoinlterdolprvos.batbrielaitteydlevel. Test Subjects: Age at study initiation: 39 10 45 days Weightat study initiation: 184 10 236 g (males); 140 to 179 g (females) No.ofanimalsper sexper dose: 20 per sex in each dose group Dra itl Assesment Report Append V 00396 Study Design: Vehicle: Chow Satellitegroups and reasons they were added: Not specified dCaliilnyic(aalmobasnedrvpamt)i.onEsapcehrfaonirmmaeld waansdfrreemqouveendcyf:roOmbsceargveeadndfoer xmaomribindeidtyat/mloearsitbounndcietwyetewkilcye. oFfotordeactomnesnutmpatnidownedeaktlaywtehrereeacfotlelr.ectBedlowoedekslaym.plBeosdfyorwheiegmhattsolwoegryeadnedtecrlimniinceadl cohnetmhiestfriryst day euvrianlaulaytsiiosnwweerreeccoolllleecctteeddffrroomm1100aanniimmaallss//sscexx//ggrroouuppdduurriinnggWWeeeekks145. and 14. Urine samples for wTeerremicnoaltliecotnedscfhoerdpuallem:it5oaynliCmaolAs/osxcixd/agsreouapndwePrFeOsSacrainfailcyesdisa;t bWleocodk s5amapnldeWseweekre14c.ollTehceteldifveorrs Serum PFOS determination. These animals were not necropsied. The remaining animals were sacrificed at Week 14 and necropsied. Organs examined at necropsy: Macroscopic examination: External surfaceofbody, all orifices, thoracic, abdominal, and cranial cavities, organs, tissues Mhiecrfoivsecro,psitcomeaxcahm,inaatnidomn:acrLoivsecrospiacndlemsaicornsoswceorpeicexlaemsiionnesdweforremeixda-mdionseedanfiomrallso.w-dToissesuaensimlaisltse;d under Tissues preserved were examined for the control and high dose groups and for animals undergoing unscheduled sacrifice. Organ weights: Adrenal, brain, kidney, liver, ovary, spleen, testis, thymus, thyroid with parathyroid T`eissospuheasgupsr,eseeyrevse,d:feAmdurrenwailt,haboortnae, mbraarirno,wc,ecHuamrd,ecreiravnixg,lacnodl,onh,eadruto,dielneuumm,,jeepjiudniudmy,miksi,dney, lgelsainodn,s,ovlairveyr,,plaunncgrewaist,hpmiatuiintsartye,mprborsotnacthei,,rlecytmupmh, nsoadlievsar(ymegsleanntde,rsicciaatnidc nmearnvdei,busleamri)n,almavemsimcaler,y stkheylreotiadlwmiutshclpea,rastkhiynr,osipdi,ntarlacchoerad,, usrpilneaerny, bsltaedmdeurm, wuitetrhusb,ovnaegimnaar,roZwy,mbsatlo'msacghl,antdests, thymus, Additional Endpoints: Serum PFOS determination: 5 animals/sex/group were sacrificed at Week 5 and Week 14 and blood samples were collected. Palmitoyl-CoA oxidase analysis: Liver samples were collected from each animal at sacrifice. Liver PFOS determination: Liver samples were collected from each animal at sacrifice. Proliferation Cell Nuclear Antigen (PCNA) evaluation: Liver samples were collected from 5 `animals/sex/group at terminal sacrifice. RESULTS NOAEL: 3 ppm (reduced weight gain, but no significant effect on absolute body weight). hLyOpAerEtLro:ph3y0apndpmva(curoeldautcieodn,boddeycrweeaisgehdt,seirnucrmecahsoeldesltiveerrolweaingdhtt,ricgelnytcreirliodbeuslar hepatocellular ratntlAsessmes Report AppiV Vos 000297 Remarks: `Baondd yfowremiaglhte:s Taensdtfmeamtaelreiaslg-rievleante1d00lopwpemr.boSdtaytiwsetiigchaltlsywseigrneifnioctaendtlfyorlomwaelremsegainvebno3dyanwdei3g0htpspm w1e0r0epnpomteddobseeggirnonuipn.g aStigWneifcikca4ntalnydlcoownetrimnueianng btohrdoyuwgehitghhetsenwdeorfethnoetesdtubdeygifnornianngimaatlWseicnkth7e cahnadncgoenstiwneuriengsptohrraoduigchaltlhyeseingndoiffitcahnet sfotrudmyalfeosr mianltehse i3n0tphepm30dpospemgdroosuepgarnodupf.orBaondiymawlesiggihvten 100 ppm. Overall body weight changes (Weeks 1 - 14) were statistically significantly lower for all treated groups. F1o0o0dp/pwamtdeorsceognrsouumpp,tifooond:cAolntshuomupgthisotnatwisatsicallolwyesrigfnoirfmicaalnetsognilvyenat3W0eaenkd 11300foprpmmalwehseinn the cloowmeprarfeododtococnonsturmopltsifoonr tmhoasntcoofnttrhoelsstautdyW.eeFkesma3l,e4s, i6n,7t,he111,00anpdp1m2.dose group had significantly Test Material Consumption: The following table summarizes the amountoftest material consumed by animals on a mg/kg/day basis: RT `Target Dose `Test Material Consumption Mean we Achieved Dose | ewe Levels (Range) [mg/kg/day] | os oasos0n | ozmeuss-oan sonasmson | asmesams ssussose zn | 1miss-0am Clinical signs (description, severity, timeof onset and duration): There were no apparent test `material-related observations noted. Hematology & Clinical Chemistry: Treatment was associated with: Tower hematocrit (100 ppm animals), higher albumin (100 ppm males), lower globulin (30 or 100 ppm males), Tower cholesterol (30 or 100 ppm males & 100 ppm females), lower triglycerides (30 or 100 ppm males & 100ppm females), higher alanine aminotransferase (100 ppm males), and higher ureanitrogen (100 ppm animals). Dra itl sessReport Appi aos _ 000298 `Emfofdeecrtastwe.erAelmliflidndeixncgesptwetrheosmeoornecphroolmesitneernotl aatnWdeterikgl1yc4etrhidaensaftoWrehiegkh-5.dosMeemaanlecso,rpwuhsiccuhlawrere tVooltruemaetmwenats. siOgtnhiefricsatnattliystliocwalelry sfoirgnhiifgicha-ndtosdeifffeemraelnecse;s twheirseficnodnisnigdewraesdoifncuindceenrttaaliannrdelnaottionship treatment-related. Ophthalmologicfindings: No treatment-related effects tMoorsteavleirteylaancedrattiimoenotfotdheaettha:l.OnTehefreemawleereinntohema3cpropsmcodpoisce ogrromiucprwoascsospaiccricfhiacnedgeosntDo aiynd5ic9atdeue that this condition was test material-related. All other animals survived to scheduled sacrifice. hGirgohs-sdpoastehaonliomgayl,s.incDiadrekncfeocai nodr saerveearsitwye:rLeaorbgseeravnedddiinfftuhseelgyladnadruklalirvsertsowmearcehoofbhsiegrhv-eddoisnesome, animals. Test material-related findings were not observed for animals in other dose groups. Organ weight changes: Liver weights (absolute and/or relative ratios) were significantly increased for animals in the 30 and 100 ppm dose groups. hHiigsht-odpoastehoalnoigmya:lsO:nseliogrhmt-otroe-omfotdehreatfeoclelnotwriinlgobturleaartomrendti-frfeulsaetehdeplaitvoecreelflfuelcatrs were observed hypertrophy, in c`meinntirmiallo-btuol-asrltioghmticdozaognuallatoirvdeinfefcursoeshise,pamtionceilmlaullahrepvaatcoucoellaltuiloanr. pCiegnmternitl,obmuilnairmahle-ptaot-oscleilglhutlar dheycpreeratsreodphayt wthaiss daolsseo.obAselrovwedinicni3d0enpcpemofamniimnailmsa,lahletphaotuogcheltlhuelairncviadceunocleatainodnsoecvceurrirtyedwiansmales rienltahteiv3e0lyplpomw dionsciedgernocuep.ofmTuhcosliavleroerfosoinoens30inptphemgfleamnadluelahrasdtmoimnaicmhawlacsoaogbusleartvievdeinnectrhoesis1.00A `ppm dose groups and was considered to be possibly related to treatment. No test material-related changes were seen in animals in the 3 ppm dose group. Additional Endpoints: `Serum PFOS determination: Analyses reported separately by Sponsor. Palmitoyl-CoA oxidase analysis: Treatment was associated with higher hepatic palmitoyl CoA oxidase for animals in the 100 ppm dose group. Liver PFOS determination: Analyses reported separately by Sponsor. Proliferation Cell Nuclear Antigen (PCNA) evaluation: Analyses will be included in the final report CONCLUSIONS dCohsreosniecxadmiientaerdy.exHpeopsautroecetloluNl-aMrehyFpOeSrtErowpahsy aasnsdocoitahteerdhweiptahtolcoewlleurlabrodeyffewcetisgwhtesreatoablsletrrveeadtmiennt haneimmaatloslofgryompatrhaem3et0earsn,d p1a0r0tipcuplmarldyosdeecgrreoauspes.d chCohlaenstgeersolinanvadrtiroiugslyccleirniicdaellcevheelmsi,swterryeaanldso obscrved for animals in the 30 and 100 ppm dose groups. > REFERENCE oCcotvaannecseulLfaobnoraamtiodroieEst,haInnoc.l 1(9N9-9.Mc1F3O-SWEe,ekT-D6i3et1a4r)yiTnoRxaitcsi.tyAUStDuIdyTEwiDthDNR-AMFetThyMlayPer2f5l,uo1r9o9-9. oo Dv mii Assent Report -Appi V "1900299 ROBUST SUMMARY - RS39 STiutllfeo:ni1c0A4c-iWdeePkotDaisestiaurmy SCahlrto(nPiFcOTSo:xiTc-i6ty29a5n)diCnarRactisn.ogSenuimcmitayrSytRuedpyowrittWhePeerkfl5u3o.rooctane TEST SUBSTANCE Identity: PFOS: T-6295 Remarks: No details in interim report METHOD Method/guideline: Not specified; presumably standard 2-year chronic toxicity and carcinogenicity trial Test type: Chronic Toxicity and Hepatocellular proliferation rate; PCaarlcmiintoogyeln-iCcoitAyowxiitdhatSiaotnel(lmiteeasAunraeloysfepseroofxSiesroumme PFOS levels; proliferation); Mitochondrial activity; Interim histopathology GLP: Yes Year: Interim report issued 1999 Species/Strain: Rat; Crl:CD' (SD) IGS BR Route of administration: Oral (dietary) Doses/concentration levels: 0, 0.5, 2.0, 5.0 20.0 ppm T-6295 in diet. Sex: Male and Female Exposure period: 104 weeks, but this is 53 week interim report Frequencyoftreatment: Daaid llibityum Control group and treatment: Basal diet Post exposure observation period: NA, one recovery group (see table below) Duration of test: 104 weeks, but this is a 53-week interim report. Statistical methods: Unknown for bioassay. Student' T-test for Palmitoyl Co-A oxidation analysis. Remarks: Test Subjects: Age at study initiation: 6-8 weeks Weight at study initiation: 100-300 grams No. ofanimalsper sex per dose: 360 males, 360 females. See table below. rat itlsess Report Append 7 000300 Dietary Level (ppm) Number of Animals per Sex per Dose | Males| Females | Week 4 sac* | Week 14 sac* | Week 53 sact* (n) 0) mon (m) 0/0 (m) 0/0 Tw eo TTeewe[ [ws [w ws [[w wenn]] Tm Tele TT | * Sacrifices at week 4 and 14 were performed to determine hepatocellular proliferation rates ((vpiaalmmeitaosyulr-eCmoeAntooxifdaptrioolni)f,ermaittioocnhcoenldlrniuaclleaacrtiavinttyigaennal(yPseCsN,A)an,dbhiioscthoepmaitchaollaongayl(ysWeesek 14 only). ** Intermediate sacrifice after at least 52 weeksoftreatment. Hepatocellular proliferation rates were determined via BrDU incorporation. Vehicle: Basal diet Hepatocellular proliferation rates, performed by Pathology Associates International. See separate write-up. Determination ofcyanide insensitive Palmitoyl-CoA oxidation . Performed by Centre for Xenobiotic Research, Universityof Dundee, Study Number XRO108. See separate write-up. Mitochondrial activity analyses Histopathology Recovery Clinical observations performed and frequency: Hematology, clinical chemistry, urinalyses, urine chemistry during weeks 4, 14, 27, and 53 Organs examined at (interim) necropsy: Week 14: adrenals, brain, eyes, kidneys, liver, mesenteric lymph node, pancreas, spleen, testes, and ovaries. 000301 Week 53: All tissues from Control and 20.0 ppm interim group members RESULTS NOAEL (NOEL) LOAEL (LOEL) None identified by testing lab None identified by testing lab. REMARKS All remarks apply for weeks 4, 14, 27, and 53, unless otherwise noted. Bweoidgyhtwseicgohmtp:arMeadletso:coAnntirmoalldsuraitntghewehiegkhses9t-5d3.oseAl(l20o.t0heprpmtr)eahtaedd sgirgonuipfsicsanhtolwyeldowneorsmigenainficbaondty differences in body weights relative to control. Fceommaplaerse:dAtnoicmoanltsroaltdtuhreihniggwheesetkdso3e-s53(.20.A0llpoptmh)erhtardeastiegdnigfriocaunptslyshloowweerdmneoasnigbnoidfiycawnetights differences in body weights relative to control Food/water consumption: M(2a0l.e0s:ppAmlt)htoeungdhednotto ccoonnsissutmenetlleyssstaftoiosdtidcaulrliynsgigwneiefikcsan1t-,2a4;ninmoalssigrneicfeiicvanitngditfhfeehriegnhceesitndfoosoed consumption relative to controls (or other treated groups) observed in weeks 28-52. Females: At highest dose (20.0 ppm) animals showed a statistically significant decrease in food consumption relative to controls during weeks 2-44. Clinical signs (description, severity, time ofonset and duration): Test lab reports no apparent test Unscheduled deaths occurred in material-related 3 males and one clinical female observations fed 20.0 ppm noted through Week 53. PFOS. 2/3 males and 1/1 fatetmrailbeusteedxthoibtihteeaddlmairngies,tmroatttiloendo,fotrhdeitfefsutsemlaytedrairakl lwieverres.obNseorvoetdh.er gross changes that could be Hematology: Nseogmreemnatrekdanbeluetrfoipnhdiilnsgsinexmcaelpetsftoraeratsetdataitst2i0c.a0llpy psimgnaitfitchaent14i-ncwreeeaksesaimnptlhienagb.soTlhueteenffuemcbtedridonfot persist, and may have been spurious. Biochem: Urea nitrogen: mildly higher (statistically significant) for males and females fed 5.0 or 20.0 ppm. Not considered adverse. Cholesterol: mildly to moderately lower for males and females fed 20.0 ppm. Not considered adverse. A{elsatnlianbesaompiinnoetsratnhsatfefriansdei:ngmsilldikleylyhiagshseorcifaotremdawlietsh fheidst2o0p.a0thpoplmog.icNaoltficnodnisnigdseorfedheapdavteorcseel,laulnadr hypertrophy and vacuolation. Glucose: mildly lower for males and females fed 20.0 ppm; statistically lower for males fed 2.0 or 5.0 ppm at week 53. ratntlAssesses Report Append va 000302 Satellite Study: Determination of cyanide insensitive Palmitoyl-CoA oxidation Ophthalmologicfindings: Nothing remarkable. Mortality and time to deat Males: no significant changes in survival up to interim (53 week) sacrifice Females: sight decrease (unknown statistical significance) in treated groups (100% vs. ~94-98%, no dose-response) Grosspathology incidence and severity: Males and Females. No clear or consistent gross observations at Week 53 sacrifice attributable to administration of test material. Organ weight changes Males: absolute and relative liver weights increased in animals treated at 20.0 ppm. Absolute and relative spleen weights decreased in males given 20 ppm. FAebmsaolleust:e slipvleeretnowbeoidgyhtwseiiggnhitfircaatnitolystdateicsrteicaasleldy astig2n0i.f0icpapntml,y aisncwraeasseadbsionlu2t0e.0lupnpgmwegiroguhpt.at 2.0, 5.0, and 20.0 ppm. Spurious, significant increases in left thyroid/parathyroid to body weight percentages observed at 5.0 or 20.0 ppm. Histopathology: Males: Centrilobular hepatocyte hypertrophy and midzonal to centrilobular vacuolation were increased in incidence and severity at 5.0 and 20.0 ppm. Fmaelmeasl,esa:ndCeinntcrrielaosbeudlacrenhtyrpielrotbruolpahryh,epwaittohcoyuttevpaciugomleanttiowne,raenodbwsietrhveldesisnstehveer2e0.e0ffpecptms tghraonupi.n CONCLUSIONS Consistent with other studies, the liver is the primary target of PFOS in rats. REFERENCE Covance Laboratories. 1999. with Perfluorooctane Sulfonic A1c0i4d-WPeoctaksDsiieutmarSyalCth(rPoFnOiSc:ToTx-i6c2i9t5y)ainnd Carcinogenicity Study Rats. Summary Report Week 53. Covance Study Number: 6329-183. Dr nitAssent Ror pperdic van 000303 ROBUST SUMMARY - RS40 Title: Oral Developmental Toxicity Study of N-E{FOSE in Rabbits (Argus 1999) TEST SUBSTANCE Identity: N- Ethyl FOSE. Lot FM 3929 Remarks: METHOD Method/Guideline followed (i.e, OECD 414, etc.): ICH Harmonized Tripartite Guideline, stages C&D GLP (Y/N): Yes Year study performed: 1999 Species/Strain: Rabbit Hra:(NZW) SPF Number of animals per dose: Twenty-two Route of administration: Oral (intubation) Dgeosstiantigonredgaiymse(nG(Dl)ist7-al2l0w(idtahyu0n).itTs)h:e Dveoheisclweewraesd2os%edTwateaenvo1l8u0mewiothf$remvle/rksge,oosnmcoesidsaily, on deionized water Doses: 0,01, 1.0, 2.5, or 3.75 mg/kg bodyweight. SBtaartliesltticsa,ltmesettahnoddsANusOeVdA: .CliIfniBcaarltldeatttasbigynivfairciaanntc@e te0s.t0f5otrhheonmoKgreusnkeailtly-.WCaolnlitsinuusoeudsfdoaltlaowbeyd by either Fischer's Exact or Dunn's Methodof Multiple Comparisons. IfANOVA significant at 0.05 then Dunnett's Test. Rweermeaexrtkras--anDietmaaills afnordadsiastceullsisteasntyudsyigwnhifeirceantthepyrowteorceoldopsaerdasmiemtielarrstaonmdadienvigartoiuopnss:anTdhekrileled ownerGeDfr2o1z.enSaamnpdlsehsipcopleldectotesdpwonesroers(e3rMu)m., Nliuvmerb,eprosoolfeddofeestusteostaalnleddp1l9acweinttahs,3,f5r,o3m,3e,acahnddoc,inth0a,t 0.1, 1.0, 2.5, and 3.75 mg/kg groups, respectively. Tkihlelreed wonerGeDex2t1r.a aSnaimmpallessfcoorlalescatteeldliwteersetsuedryuwmh,elrievetr,hepyoowleerdefdeotsuesedssainmidlaprlatcoenmtaais,n fgrroomupesacahnd PO -------- van 000304 doe, and that $i 0w,e0r.e1,fr1.o0z,en2.a5,ndansdhi3p.p7e5dmtgo/skpgongsroorup(s3,M)r.espNeuctmibveelrys.ofdoes totalled 19 with 3,5, 3,3, RESULTS NOAEL (dose and effect) - maternal and developmental: Matemal 0.1 mg/kg. Developmental 1.0 mg/ke. LOAEL (dose and effect)~ maternal and developmental: Matemal. 1.0 mg/kg reduced weight gain on GD 7-10only. Developmental 2.5 mg/kg - abortions dTuorxiincgrGesDpo7n-s1e0leifnfe1c.t0smbgy/kdgosdeosle.evTeh-lermeatwearsnaaln:acMtautaelrwneailgwhetigdhetc:reMaeseaninwtehiegmhteagnaiBn rWediunctehde a2.l5soasnidgn3i.f7i5camntgl/ykdgedcroesaesgerdoduuprsinatgtthheesGeDti7m-e1p0earnioddGs Dat t1h0e-s1e4tpweoridoodsse.s.Food consumption was Toxic response/effects by dose level - developmental. There were 1,2 and abortions in the 0, 2.5 and 3.75 mg/kg dose groups. Statistical results: Results discussed above were statistically significant aRestmaatirsktisca--llAydhdiigthieornianlciidnefnocreomfatliaotne troesaodrepqtiuoantselinytahsese3s.s75thmegd/aktga:grTohuep;rhepoowretvestra,tetshet.here was incidenceoftotal resorption was similar to controls. CONCLUSIONS Comment on author's conclusions and the GD 7-10 time period at the 1.0 mg/kg whether you agree: The dose is the sole basis for reduced body assuming this weight dose is gain a in LOAEL. While plausible, it is very weak data upon which to establish a LOAEL. Tinhethsetfuadcyeoafuothnoersaabtorritbiuotneitnheth2e caobnotrrtoilosn.sTahte2r.e5 wmegr/ekg$ taobobretiroenlsataetdtthoeEntexFtOhSiEgheexrpodsousree.thTahtiiss, Gliikveelyncthheembiocadlylywerieglahttedl.osAsbaorntdiroendsuacreedlfisotoedd ibnytatkheeisntutdhey daoutehsoirtssaesemasdemvoerleoppmleaunstiablleeftfeoctb.e: associated with maternal toxicity. REFERENCE Final Argus Report, protocol 418-010, Oral Developmental Toxicity Studyof N-EFOSE in Rabbits. 3M 6316.8. CD#1 00012621.pdf Dr nitAssentReport ppeic van - 000305 OTHER Need to establish status of tissues taken for possible analytical work. af iilAvsssment RepAopprentd V 560306 ROBUST SUMMARY - RS41 TITLE: Oral Teratology Study of FM3422 in Rats - Experiment No. 0680TR0010 [N-E(FOSE] TEST SUBSTANCE Identity: N-EtFOSE (FM3422) NR-eEmtaFrOkSsE:,Mwaittehri3a%l ipdreinmtairfiieldy aasCF6MF3O4S2E2,alLcootho7l84p.erFM3M34m2e2miodeonftiDf.RieRdiacsk9e6r%dnaatrerdow range Decemberl0,1980. METHOD Method/Guideline followed (i.e, specified but appears to be similar OECD 414, in design to etc): OECD Actual 414. guideline followed was not GJaLnuPar(yY,/N1)9:66T(h"eGupirdoecleidnuersefcoormRpelpireosduwcittihotnheStguednieersalforreScaofmemteynEdvaatliuoantsioonfotfheDrFuDgAs fiosrsuHeudmiann Uasned")S.afeTthyeEsvtaulduyatwiaosn cLaobnodruacttoerdy'asccSotradnidnagrdtoOtpheera1t9i7n8gGPoroocdedLuraebso.ratory Practice regulations Year study performed: 1980 Species/Strain: Charles River Sprague-Dawley rats Number of animals per dose: 22 Route of administration: Gavage Dadomsiinnigstreergeidmteesnt (mlaistterailallwiinthcournnitosf)l:bFyoguarvaggroeuopnsogfes2t2atitoinmed-amyast6e-d15S.prDaogsuees-Dwaewrleeaydrjautsstewdere according to the most recent recorded body weight. Doses: 0, 25, 37.5, and 75 mg/kg/day S`tgaetniesrtaitceadlrmaentdhoomdnsuumsbeedr:sTthabele.aniTmhaelsstwaetirsetiacaslsimgentehdocdasgteosbaeccuosreddinfgortaonaalcyosmipsoutferth-e data are: oDufninmeptlta'nsta{ttieostn sfiotreds aamndannudmpbueprwoefigchotrsp,ornaumlubteear;oCfhfietsuqsueasr,enfuomrbpeerrcoefntreasbonroprtmiaolnitsiiteess., number RFeMma3r42k2s w~aDsetaadimlinainsdtedriesdciunsscoanmyoisligbnyifgiacvaantgeprtootfoocuorlgpraoruapmsoefte2r2s tainmde-dmeavtieadtiSopnrsa:gueDgeaswtlateiyonra(tGsowrteniegrh,in1g9810)7.5-T26h1e3,anaitmdaolssewseorfe0,do2s5e,d37a.c5c,oradnidng75atmag/ckongs/tdaanyt odnosdeayvsol6u-1m5e ooff comlloi/fnkincgaoalfsAibgsonssd.yenwBeoRiedgpyohrttwaeAinpgpdehdotibsssweerrveedredaciolrydefdroomn ddaayys33t,h6r,o9u,gh12d,ay152,0anodf 2ge0sotfatgieosntaftoiroanvbananonerdmtahle 000307 rcaotsn.tenAtlsl waenriemaelxsawmeirneedsafcorriftihceednuomnbdearyof20cborypcoerravilcuatelad,insulomcbaetiroonfavnidabtlhee aonvadrineosn,-vuitearbileand sfeetxuesdesa,nndusmubbejreocfterdestoorepxttieornnalsitgerso,sasnndecnruompbsey.r of implantation Approximately sites. Fetuses were weighed one-thirdof the fetuses was and friexmeadinininBgoufietnu'ssessowleurtieosnuabnjdecetxedam1i0naesdkefloertvailsecexraamlinaabtnoiromnaulsitiinegsabliyzafrrienerheda.nd sectioning, The RESULTS NAONAOEALEL(doofse25anmdg/ekfgfe/cdta)y-fmoratmeartenranlalantdoxidceivteylwoapsmeinntdiacla:ted. IAflNenOsAeEffLectfsoradreevceolnospimdeenrteadlatnoaxritciiftayctc,otuhledrenoits abeNeOsAtaEblLisohfed25whmeg/nkgl,ens effects are considered. LOAEL (dose and effect) ~ maternal and developmental: Matemal: 37.5 based on significant reductions occurred in 3 rats at the 75 mg/kg dose. in mean body weights during gestation. Death pDaertviecluolpamrleyntsatle:me3b7r.a5e.baIsnecdidoenncceleofft pballoaotdeirnetdhuecekdidfneteayl pbaordeynwcehiygmhatwaansd ssikgenlieftiaclacnhtlayngeelesvated atthe 75 mg/kg dose. TduorxiincgrGesDpo1n2s-e/2e0faftectthse hbiyghd-odsoeselegvrelou-pmaotfe1r0namlg:/kSgi/gdnaiyf.icant reductions in mean body weights `dTeovxeilcoprmesepnotnasle/veafrfieatcitosnbsyanddosaebnloervmeall-itdieevseolfotphmeenlteanlso:fUtnhueseuyaellwyehriegohbisnecrivdeednciensalolfFM-3422 groups. Statistical results: controls (Dunnett's Mean test p maternal < 0.05). body weights were statistically significantly lower than Mean liter P<0.05). data and pup weights were not significantly different from controls (Dunnett's test Np<u0m.0b5e),roffetuses with gross findings were not significantly different from controls (Chi-square Number controls and percentof fetuses (Chi-square p<0.05). with skeleton findings were not significantly different from Nseucmobnedarraynldenpseracbeenrtraotfifoentsuwseersewistighniifnitceamnatllyfihnidgihnegrst-ha-ndecvonetlrooplmse(nCthail-slqeunsaraebnpo<r0m.a0l5i)t.ies with Rapepmeaarraknsce~,Tlhertehearrgayt,saitnaxtihae,hbilgohoddoyssetogorlosuapnddieedn.crCulsitneicdabllsoiogdnsarinoutnhdesteheanniamraesl.s Siingcnlsudoefd thin `maternal gestation toxicity were period in rats not seen from the in other rais. 37,5 and 75 Significant reductions in mean body mg/kg groups. There were no effects weights seen on the DrIti Assent Report AppenVd vais 000308 nmuamtbeemrasloofvvairayb,lmeemaanlen,umfebmearloe,fainmdpltaontatlatfieotnusseisteast, corpora lutea, any dose. resorption sites and the mean sMteatainstifceatlallywseiiggnihfticwaanst isingcnriefaisceanitnlcylelfotwpearlattheaticnotnhteromlivdalaunedshiingahlldotrseeatwehdegrreoauspsn.oTclheeftwpaaslaates swoemreetsiemeensaitntchiedecnoncterionl sotrelmoewbrdaocsem.alTfhoermsattudiyonasutahtoarlsl tdreesactrmiebnetd daonseisn;crsetaasteedinasserveelraitteyd atnod exposure exposure to to FM the t3e4st22s.ubOsttahnecres.keAlentoatlaabbleersraitginoonfs dweevreeloalpsmoensttaatledtoaxsicbietiynogbassesrovceidatiend with all Fm 3422 glorcoaulpiszecdontsoitshteedaroefaoafbtnohremaelmibtrieysoonfatlhleenlsennsuocfletuhse, eaylet.hoAulglheayevaarbineotrymoaflimtoirepshaoplpoegairceadl to be aappppeeaarreandcteosbweearne aprrreessetntinwdietvhienlotphamtenlotcoafttihone. pArcicmoarrdyilnegnstofitbheersauftohromrsi,ngthtihseaebmnborrmyaolniatlylens snuucrlreouusn.diSnegctohnedaabrnyolremnaslfeibmebrrdyeovneallopnumcelnetusp.roAgrnesasmeednndomremnatlltyo etxhceerpetsuilmtmseadnidatdeilsycussion sseeccttiioonnicnognacnldudtehse trhaantgteohefggrroossssfilnednisnogbosefarvalteinosncsleafnt dwathse adnifafretirfeancctescraematoendgbythefrdeoesheangdroup finrceicdheanncdessewcteiroenidnugeatnodththeemlainmniteartiaonnds ifnrheeqrueenntcyinivniwshuailcihzitnhgetlheensemclberfytoanratilfancutclweauss.creAated by subsequent study was not able to repeat this finding. CONCLUSIONS tChoemsmtuednytauotnhoarsu.thHoorw'sevceornciltuissiboenlsieavnedd twhhaettthheerleynosudeafgercete:isRaenvairetwifearctgaesnseorcailaltyeadgwrietehs twhieth wmietthhoPdFOoSf.frOetehhearnsdtusdeicetsioinninogt.heTrhilasbloernastoerfifeescthawvaesnaelvseororbespeorrvteedd ilnentshiesffleactbso.raAtorsyumwimtahrsytuodfies the lens issue in Study Director, the EG GRoirktenrerL,abdoartaetdorNioevseims bceonrt6a,in1e9d81i.n a memorandum to the file written by the REFERENCE 3Go4r2t2neinr REaGt,s"L,aJnapnrueacrhyt 2E2G,,19C8a1s.eEMxTp.erRiimkeenrtLNaubmorbaetro:rie0s6,80ITnRc.O0"0O1r0a.l TCeDraRtoOloMgy0S0t0u1d2y29o1f.FpMdf- DGaotret"n,er3pEpG,.NMoveemmobetor Study Files 6, 1981. titled "Fetal Rat Lens Artifact ~ Summaryof Developments to Ricker DR. 3M memo to WC McCormick. Dated December 10, 1980. CD ROM 00012992.pdf OTHER Any other information deemed appropriate: None fr -- ---- ee-------------- 360309 ROBUST SUMMARY - RS42 Title: Oral (GAVAGE) Developmental Toxicity StudyofN-EtFOSE in Rats (Argus 1998) TEST SUBSTANCE Identity: N- Ethyl FOSE. Lot FM 3929 Remarks: Material, room temperature. described as a waxy solid, was received on May 28, 1998 and stored at METHOD Method/Guideline followed (i.e., OECD HarmonizedTripartite Guidelines stages C 414, &D etc.): The requirementsofthe ICH were used as the basis for the study design. The Dpuarwploesye)orfattsheasntduddyevwealsoptomednetteocft aedmvberrsyeoeafnfdectfsettuosNc-onEs(eFqOuSenEtitnoperxepgonsaunrteCofRt:hCeDd(aSmprfargoume the periodof implantation to hard palate closure. (GGLLPP)(Yr/egNu)l:atiYoenssoTfhtehsetuUdSy wFaosodcoanndduDctreudgiAndmcionmipsltiraantcieonwi(tFhDAth)e,GtoheodJaLpaabnoersaetMoirnyiPsrtarcytiocfe sHieganlitfhicaanntddWeevlifaatrieon(sMfrEoWm)thaendGLthPe rEeugruolpateiaonnsEcthoantoamfifcectCeodmtmhuenqiutalyit(yEEoCr)i.nteTghreitryeowfetrheeistoudy. Quality has been Assurance Unit documented. findings derived from the inspections during the conduct of this study Year study performed: 1998 Species/Strain: Rat. Sprague Dawley [Crl:CDBR VAF Plus] tNiussmubesewreorfeatnoibmealcsolpleecrteddosfeo:r Twenty-five in main study, possible future analyses of 3 or ina satelite study where N-E(FOSE or metabolites Routeof administration: Oral (intubation) gDeosstiantigonredgaiymse(nGD(l)st6-a1ll7w(idtahy u0n).itTs)h:e Rveahtisclweerweasdo2s%edTawteaevnol1u8m0ewiotf5h rmelv/ekrgs,e oosnmcoesdiasily, on deionized water eDfofseecsts:w0e,re1,o5b,se10r,veodr 2at01m0g/mkg/gkbgodbyw/wdeaiyghatn.dBhaisgehedr.on dose-range study where bodyweight BSatrattliesttti'csa,l tmeestthaonddsAuNseOd:VAC.linIifcaBlardtlaettatbsyigvnairfiicaanncte@test0.f0o5r thhoemnogKernuesiktalyl.-CWoanltliinsuuosuesddfaotlalboywed by either Fischer's Exact 0.05 then Dunnett's Test. or Dunn's Method of Multiple Comparisons. If ANOVA significant at Dr ilAsset Ror Append ee var 000310 gRreomuaprskasnTdhkeilrleedwoenreGeDxt1r8a.aSnaimmapllsesfocrolalseactteeldliwteersetusdeyrwuhm,erleivetrh,eypowoelreeddfoesteusdessiamnidlaprltaocemnataisn, from cach dam, that were 3,5,3,3, 2nd 5in0, 1,5, frozen and 10, and 20 smhgi/pkpgedgrtoousppso,nrseosrpe(c3tiMv)e.lyN.umbersof dams totalled 19 with aFcecmlailmeatriaotns pweerrieodo,bosnerGveDd 0twaincde dGaDily4faonrdvidaabiilliytyd.urBiongdythweediogshatgseweanrde proesctorddoesdawgeeepkelryioddur(iGnDg. 6-20). 20. Food consumption was recorded on GD 0, 4, and on alternate days thereafter through GD RESULTS NOAEL (dose and effect) - maternal and developmental: Maternal 5 mg/kg. Developmental 5 mg/kg. LOAEL (dose and effect) - maternal and developmental: Maternal. 10 mg/k-g reduced weight gain. Developmental 10 mg/kg reduced fetal body weight and delays in caudal vertebra ossification. TduorxiincgrGesDpo8n-s1e2/eifnfe1c0tsmgb/ykdgodsoesel.eRvee-dlumcaetderfentaall:weMiagthetrngaalinwediugrhti:ngMteheanGDwe6i-g2h0t pgeariinordeadtuctheed 2in0tmhge/2k0gmdgo/skegggroruopu.p.Food consumption was also significantly decreased during this time period m`Tgo/xkicg raensdpodneslealyeefdfeocstssifbicyatdioosneinlecvaeuld-adlevveerlteobprmaee.ntIanlc.reRaesdeudciendcifdeetanlceboodfywwaeviyghritbsatin1020anmdg2/0kg group. Statistical results: Results discussed above were statistically significant tRheemrearwekrseNnoocldienaitchasl,spirgensmaattutrriebdueteldivteorieefsfeocrtsaobforttheiontseswtemraeteoribasle.rvMeidnidmurailnagntdhetrsatnusdiyenatn(dGD 8pe-r1s0i)stdeenctraetas1e0smign/mkagtedronsael wbhoedryewtehiegrhetwgaasinawseirgenisfeiecannattddeocsreesasoefdSumrgi/nkgg,theEfGfeDct8s-w1e2rpeermioorde rfeodlulcoewdedwbeyigahntdgianicnrienastehde w2e0igmhgt/kggaignrdouurpinthgrGouDgh1o4u-t16t.heThGeDre6w-a20spaecrtiuoadl.weFiogohdt cloosnssuomrption decreases were observed observed on body weight in the 10 and 20 mg/kg dose groups in a pattern similar to the effects gFretoaulpsb.oFdeyrtwieliitgyhatnwdafsetsailgnviiafbiiclainttylyparreadmuecteedriwnelritetecrosmfpraormabdlaemsacirnostsheth1e0caonntdro2l0 amngd/kNg- dose EfrtohmyItFheOS1E0 garnodup2s0.mSgig/nkigfigcraonutpdse;laanysinicnroesassiefiicnattihoenoifncciaduednacelovferwtaevbryaeriwbserweasnoatlesdo isnefnetiunsetshe 20 mg/kg fetuses. All other gross, visceral or skeletal observations (malformation and -------- vais 000311 variations)werejudged to be unrelated to exposure to N-EtFOSE. CONCLUSIONS Comment on conclusions. author's conclusions and whether you agree: Agree with the study authors" REFERENCE RFaitnsa,l Dreepcoertm,bPerrot1o7c,ol1949188.-031M1,63O1r6a.l7.(GCaDva#g1e)00D0e1v2e3l4o5pmpednftal Toxicity Study ofN-EFOSE in OTHER Need to establish statusoftissues taken for possible analytical work. raf nitAsscssment Report Append V 600312 ROBUST SUMMARY - RS43 PTIETRLIEN:ATCAOLM/BPIONSETDNAOTRAALLR(EGPARVOADGUEC)TFIEORTNITLOITXYI,CIDTEYVSETLUODPYMEONFTNA-LEtAFNOSDE IN RATS 3M 418-009; ARGUS RESEARCH LABORATORIES STUDY NUMBER: 6295.9, 1999, TEST SUBSTANCE Identity: N-E(FOSE alcohol tReemmpaerraktsur:e.LoPtrnepuamrbeedrsFusMp-e3n9si2o9nswawserreecsetiovreedd oatnrMoaoym 2t0e,mp1e9r9a8t,uarendovsetronriegdhta,t rIonofmormation regarding Sponsor. the purity, identity, strength and compositionof the test article is on file with the METHOD AMdemtihnoids/tGrautiidoenl(inFeDAf)olwleorweedu:sAedmaosdiafbiacsaitsiofnoorftthheestruedqyudierseimgenn.tsof the US Food and Drug `Type of study: Two-generation reproductive toxicity. (GGLLPP)(Yr/egNu)l:atYieosn.soTfhtehestUudSyFwoaosdcaonndduDcrtuegd Aidnmcionmipsltiraatnicoenw(iFtDhAt)h,e GthoeoJdapLaanbeosreatMoirnyisPtrracytiocfe. sHieganlitfhicaanntddWeevlifaatrieon(sMfrHoWm)thaendGLthPe rEeugruolpateiaonnsEcthoantoamfifecctCeodmtmhuenqiutalyit(yEoErC)i.nteTghreitryeowfetrheensotudy. Quality has been Assurance Unit documented. findings derived from the inspections during the conductof this study Year study performed: 1999 Species/Strain: Rat. Sprague Dawley [Crl:CDBR VAF Plus] Sex (males/females/both): Both. fNeummalbeesrfoorfdaentiemramilnsaptieorndoofsree:prF,od=uc3t5iv[e25stfaetmuaslaetsDfGor f1u0l]l. eFv1alhuaadti2o5noefacFh,gseenxe,rpaetriodno;se1.0 Route of administration: Oral (gavage). aDdomsiinnigstreergedimEeFnO(lSisEt ablyl wgiatvhagueniftosr):siFxidveaygsropruiposrotfo c35ohraabtistapteirosnexanpedrdduorsienggr1o4udpaywseorfemating. fTermeaaltemerantts winerFematrleeaterdatdsaciolynttihnruoeudghuontuitl goensetadtiaoyn,bepfaorrteursiatcironi,fiacned(alpapctraotxioinm.atFe,lyrat6s3rdeacyesivteodtal); daily gavage commencing on LD 22 and each day thereafter until sacrificed. [-------- vam 000313 - Doses: 0, 1,5, 10, 15 mg/kg bw/day Premating exposure period for males/females F,, F,: F, males were dosed daily beginning 28 days before cohabitation, during mating, and until the dayofsacrifice fora totalof ~60 days dosing. F, sacrificed. females were dosed for F, rats exposed in utero 28 days before cohabitation and during lactation; direct and daily thereafter dosing commenced until at weaning and continued until their litters were weaned. Statistical methods `Homogeneityof the used: Proportion data Binomial Distribution. were analyzed using the Continuous data (body Variance Test weights, body for weight changes, and feed consumption) were analyzed using Bartlett's Test of Homogeneity of Variance and AnalofyVs ariiansce (ANOVA).If the ANOVA was significant(p < 0.05), Dunnett's Test was used to identify the statistical ANOVA was not appropriate, the Kruskal-Wallis significanceof Test was used. the In individual groups. If the cases where the Kruskal- Wallis Test was statistically significant (p 0.05), Dunn's Methodof Multiple Comparisons `was used to identify the statistical significanceof the individual groups. If there were greater ntheacnro7p5sy%dtaitesa, fFoirshtehre'psuEpxs,acwthTiecsht wwearse ussteid.llbFoimsohrerfsouEnxdacdteaTde.stDawtaasoabltsaoiunseeddattoCeevsaalrueaatne- bseehctaivoinoirnagl, dnaattaurianlvdoellviivnegryd,ispcrreet-ewedaantian(gnruemfbleerxo/pfhycsoircpalordaevluetleoa,pmneunmtbalerdoaftpauapnds ppoesrtl-iwteera,nitrnigals 10 a criterion) were evaluated by the Kruskal-Wallis Test. Remarks ~ Detail and discuss any significant protocol parameters and deviations: SSteuedyT.able [Schema on page 1-4ofthe Report to be reproduced] for schematic description of F, Generation: Parental rats (F,) were observed twice dailyforclinical signs. Body weights and food consumption values were recorded weekly during the treatment period in male rats; andweekly during mating and then daily during gestation, and on lactation days 1, 4,7, 10, 14, and at sacrifice in female rats. necropsicd. Each dosage group consistedoftwosetsof female rats. Onesetconsistedofthe first ten female rats `with confirmationofmating that were to determine the number of corpora dosed until `gestation lutea, implantations, day and (GD) 10, number sacrificed, and of viable and necropsied non-viable embryos. The remaining females comprised the second set, which delivered naturally. During the 21-day lactation period, the dams were evaluated for clinical signs during parturition and length of gestation, and the Pup observations n d each uring litter the 2 was 1-da evaluated y lactation at least period twice daily for size and included physical signs, pup body viability at birth. weights,`nursing behavior, surface righting reflex, righting reflex. Pupil constriction pina unfolding, eye was evaluated only on opening, lactation acoustic startle response and air day 21. On lactation day 4, liters were randomly culled to four male and four female pups. The remaining pups were sacrificed and Ort ttascent pends van 000314 (TlhaectaFtyiomnaldeayrats1).werTehseacrteisftiecse,d eapniddindeycmriodpessi,edparfotsetratteh,e aennddofsdemoisnianlgvaetsitchleestiwmeeroef wpaeritguhreidt.ion Evaluations of sperm number, motility, and morphology were not included in the protocol. nTehceroFp,sigced.nerOavtairoinesfewmearleesexthaamtidneeldivaesraedbonvaetuarnadlltyhewenre usacraminfidcdebidstore nibluatrcitoantioofn idmapyla(nLtDat)io2n1saitneds wwearserceoclorldeecdt.ed fTrhoemlSivmeralferormatesatchhatpharaedntmaalteradt awnads frreommovedf,emwaeliegrhaetsdoanndLaDna2l1yzfeodr.phBalromoacdoskaimnpetliecs aTnhaleysfiisn;allrievseurlstsfroofmthtehseepaunpaslyfsreosmwtehreelniotterasovafitlhabelseeatfitvheedtaimmseofwtehriesalrseoviceowl.lected for analysis F, Generation: gSrionucpesF,,ognelnyerthaeti1onanpdupS vmiga/biklgi/tydawyasdossiaggniefigcraonutplsy rweedruecceadrriinetdhient1o0atnhedse15comngd/gkegn/edraaytidoon.sages dTowseenstyo-ffi1,veanFd, 5gemnge/rkatgi/odnaryatbsepgeirnnsienxgpoenr LdoDse22graonudpcwoenrteinaudimnigntishtreoruegdh PthFeOdSaybybegfaovraegseacartifice. aAvto2i4dadnacyesopafraagdei,gmo.neOrnatLpeDr2s8e,xfpeemrallietteevrailnueaaticohndsocsoamgemegnrcouepdwtaosdetteestremdinien tahpeasasgieovef vaginal speaptaernactyioann.dOonneLrDat 3p4e,r msaelxepreart lietvtearluwaatsioenvacloumatmeednicneadwtaotedre-tfeirllmeidneM-tmheazageeoonf pLrDep7u0t.ial wAistshigenvmiedenntcteoocfomhaabtiitnagtiwoenrweitchoinnsiedaecrheddotosabgeeagtrGoDup0beagnadnaosnsiagpnperdotxoiminadtievliyduLalDh9o0.usiFnegmafolres ntheecrroepmsaiienddaenrodfetvhaeluadtoesdiansgdpeesrciordi.beTdhienFt,hegeFnOergaetnieornatmioanl.e rAaltls wF,ergeensearcartiifoincefdeamfatleersmawteirneg, saalclroiwfeicdedtoadnedlinveecrrnoaptsuireadlloynaLndDr2a1i.scAlliltteFr,s ugnetnielraLtDio2n1.pupDsawmesrtehastacdreilfiicveedr,ednelcirtoeprssiweedr,eand examined on LD 21 as previously described for the F, generation pups. RESULTS NOAEL -F,, F,, and F: F, Img/kg bw/day; reproductive NOAEL 5 mg/kg. F< 1 mg/kg bw/day based on body weight effects; reproductive Sme/kg . F, | mg/kg bwiday. LOAEL (dose and effect) ~ F., F,, and F: FS F, 1 mg/kg mg/kg based based on on body body weight weight effects; effects, reproductive greater than 5 10 mg/kg based on mg/kg, the highest stillbirths. dose tested; F, 5 mg/kg. Based on effects on viability & growth Toxic responseleffects by dose level: FF: F, had reductions in food consumption and body weight gain at 10 and 15 mg/kg bw/day. DrIiAsses Ror Append vz 000313 Flo,ssh,adrerdeudcuecdtilointsteinsibzeo,dpyuwpeivigahbtilgitayi,ngarto5wtmhg/akngd;sautrv1i0vaalnd 15 mg/kg there was preimplantation mFe\//Fk:g Idnostehse.FI,ntthheereF,wetrheererewdeurcteisotnisllibnirftehsedancdonrseudmupcttiioonns ainndlibttoedr ysiwzee,igphutpgvaiianbialtittyh,eg1roawntdh, and survival in the 5 mg/kg dose group. Statistical evidenced droesseulrtes:spIonnstehechmaarianct,erriesstuilctss.summarized above were statistically significant or Remarks~ Additional information to adequately assess the data: F, Generation. dGoesneertahlerteoxwiacistya.n Nimopatirreeatdmreingthtrienlgatreedfldeexa,tthhseorcecwuerrreednionterietahtemresnetx-.reIlnatmeadlcelirnaitcsaaltstihgens15ofmg/kg twoexriceitoyb.seSrigvneidfiicnafnetmianlcerseaisnesthien5l,oc1a0l,iaznedd a1l5opmegc/ikagd/udraiyngdopsrae-gmeatgrionugp,s.gesRteadtuicont,ioannsdilnacmtaalteioannd pfheamsaelseobfotdhyewsetiudgyh.t Rgeadinusctoicocnusrriendfionodthceo5n,su1m0patnidon15wemrge/kcgon/sdiasytednotslaygseegenroiunptsheth1r0ouagnhdou1t5all mwegi/gkhgtsgrwoeurpesraendducferdeqiunenmtallyessefernoimntthhee,5 m1g0/akngdg1r5oumpg/thkrgogurgohuopust.tOhbessetruvdya.tiToenrsmfionuanldbaotdy necropsy in both sexes were unrelated to treatment. RnoetprsoedeuncitnivaenyTodxoicsietyg.roMuapl.eR-aretlsaftreodmeftfheect1s5omnym/aktginggroourpawneyrfeerhtailditsytaptairsatmiceatlelryssiegvnailfuiactaentd were rauetdhuocrtsiotnoibneacbhseomliutcealsleymirenlaaltedv.esiWchlielaenad dperocsrteaatseewienipgrhotsttahtaetawnedreseimnitneraplrevteesdicblye wtheeigshttudwyas ssiegennifoincaanntlaybdsioflfuetreenbtasfirso,mwchoenntroelxsp.reEsvsaelduaatsiaonnoofrgsapnertombnoudmybewre,igmhottirlaittiyooitrwmaosrpnhootlogy was not partofthe study protocol Eresdturcotuisocnysclininlgi,ttemraatvienrgaagensd ffoerrtiilmiptlyawnetarteiosinmsilaanrdalmivoenegmbalrlygorsouwpes.reStoabtsiestrivceadlliynstihgeni1f5icmangt/kg nfoetmeadleisnetxheam1i5nmegd/okngDdoGse10g.rAoupreidnuctehed mnauimnbeporrotifoinmopfltahnteatsitoundys,itwehsearnedfleimtaerlessizbeiwrtahsedaltshoeir litters. The gestation duration was significantly reduced in the 5, 10, and 15 mg/kg dose. F, Generation oDtehveerlsohpamdenrteadlucTeodxilciitteyr.sFizoeuranfdempaoloerspiunpthveiab1i5limtgy;/kagl gpruopuspwheardendoealdivbeyboDrLn p5.upTshean1d0tmhge/kg cgarnonuipbahlaidzeadn oinncDreLas1e;daidndictiidoennacleopfusptsildlibeodrninptuhpeso2-r4,p4u-p7s atnhadt 8d-i1e4d doarywelarcetaptrioensupemreidods. Vviaalbuielsitayrein92d.e8x,v9a9l.u1e,s92d.e0m,3o0n.s2traatnedth1e.s2t.e0e%pfnoartuthreeo0f,t1h,e5,do1s0ea-nrdes1p5onmsge/fkogr pdouspe,morretsapleicttyi;vely. raf nia sesame Report Append vam 000316 ---- ee-------- mDogsgerdoeuppse.ndTehnetreanwdasstaatlissotiacatlelyndseignnciyfifcoarnrterdeudcuecdedpubpodweyiwgehitgihntsthweer| emgse/ekng in the , 10 and group. These 15. cwoenisgihstteenftfleyctrsevpeerasliesdteddeltahyrsouinghpouuptdtehevellaoctpamteinontpdeurriiodn.g tAhenlacutatimoofnbpbieorlieoodg.ircianllimtetearssubroersn of imnoctlhuedresdtshuartfraecceeriivgehdti$ngorre1f0lemx,g/pkingnEatuFnfOoSlEdi(nagl,l e1y5e mopge/nkigngp,upascowuestriecdsetaardtlbeyreDsLpon5)s.e,Thaensdeair driegvhetilnogp.mAenttrawnassieunlttdiemaltaeyliynaacgheioefvepdinfnoracuancfhoolfditnhgesweasinadliscoesseiennalilngtrhoeup|s.mgD/ukeg tgorosuepv.erNeoprumpal imonrvtoallviitnygdtuhreisnugrvlaicvtiantgionratins wthoeul1d0 omcgc/ukrgagnrdoutpheiyt wwearsedeeuttehramniinzeedd.tThawtennotyfufritvheercascthu,dimeasle and TfheimsaldeosFi,nrgatrsecgoimmmenencconetdinrueecdeitvhirnogudgahiltyhegagvraogwethdoasnedsomaft0i,ng1,paenrdiod ming/bkotghEs(eFxeOsSaEnadtiwneaning, females through gestation and 21 days of nursing and lactation. vInagtihneaplospatt-ewnecayniinngthpeer1ioadn,daSgemogf/pkrgepduotsiealgrsoeupparsawtiaosnsiinmitlhaer|tomgco/nktgroglrpouupps.anPdreaptuttaiianlment of cseopnasriadteiroendwnaots tsoigbneiftiocxainctollyodgeilcaalyleydiimnptohreta5nmtgb/yktghebystaupdpyraouxtihmoarst.elTywooneneduaryo;ltohgiiscawlastests were. performed maze at 70 on one daysof rat per sex per liter; age. No chemically passive related avoidance at 28 days of effects were observed. age and a water-filled M nReecprroodpuscytiinvmeaPleersfofrrmoamnctehe. 5Bomdgy/kwgeiggrhoutpw.aMsasliegsniifnictahnetl|ymrge/dkugcegdraotutpicmoeomfmownelaynihnagdarnedduatced rbeodduycewdeiignhtthega5i,nsbudtunroitngthtehe1,fimrsgt/mkogngtrhouopf.thIen pfoesmtal-ewseafnrionmg tpheeriSodm.gF/okogdgrcoounps,umwpeitgihotn wwaass reduced at weaning gestation generally and was stihgrnoiufgichaonuttlythreedpurec-ecdohinabtihteat1ioanndpe5rimodg./kBgodgryouwpesi.ghTthigsairnedduucrtiinogn in wweeiigghhtt egfafienctpse.rsAits9te0ddtahyrsouogfhaoguet mlaacltaetsioan.ndRfeedmuacleeds wfeorode cmaotnesdu.mpAtfitoern mwaatsincognmsaislteesntwewritehkiblloeddy tahnedynweecrreopksiillde.d Faenmdanleecsrowpesrieeda.llNooweedffteoctlsitotenr maantdinnugrasendthfeeirrtiyliotuynwgerunetiolbsDeLrv2e1d aitnwchitihcehr steixm.e No toxicological findings were noted at necropsy. F, Generation gNroouspi.gnHiofiwceavnetre,fftehcet nonumlbitetrerosifzde,amnsuwmibtehrosftillilvboernorpuspisllwbaosrspiugnpisfiwcaasntnlyotiendcrienatsheed 1atotrhe m5g/kg dmugr/ikngg dtohseeD.LTh1etnhuomugbher1o4fpepruipodsd.eatVhisaboirliptryeisnudmeexdwcaasnn9i8b.a8l,i9z7e.d1,waasndsi8g5n.i1fi%canitnl0y,el1,evaantded smigg/nikfgicdaonstelygrroeudpusc,edresatpebcitritvhelayn;d tthherSoumgghouwtasthseiglnaicftiatciaonntlpyerreidoudceidn.thPeu5p mwge/ikghgtgwroausp.alCsloinical and necropsy findings in the F,pups were unremarkable. CONCLUSIONS Comment on author's conclusions and Drnialnie.esses ReRporpt ort AppAepnpdi whether you agree: Generally agree. Do not $v6e0317 suenpdaerrasttiaonnditshneotbarseilsatfeodr tdoetcehremmiincianlgetxhpatostuhreeslaitghtmbgu/tkgsi.gnWihfiilcaentsudcehlaaydienlaaygesohfopurledpnuottiable `cmoantsuirdaetrioendala rdeeplraoydsusceteinveateftfheicst,doist ei.s entirely consistent with reduced body weight and other REFERENCE Christian M, Hoberman A & York R. Argus Research Laboratories. COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL PRrEotPoRcoOlD4U1C8-T0I09O;NSTTOUXDIYCINTUYMBSETRU:DY63O16F.5N,-EtFOSE IN RATS. Final Report, 30 June, 1999. Oat Ameprorr pends 0i00318 ROBUST SUMMARY - RS44 RTiAtlBeB:IOTRSA-L3(MSTT-6O2M95A.C10H,TAURBGEU)SDERVEESELAORPCMHENLTAABLORTAOTXOIRCIIETYS SSTTUUDDYYONFUPMFBOESR:IN| 418012, 1999. TEST SUBSTANCE Identity: Potassium Perfluorooctylsulfonate (PFOS), CAS No. 2795-393 DRoecmuamreknst:atiPoFnOfSile-d Laolton2g17w,it9h8f.i4n%alpruerpoert(,SMNoDteA:naSlaytmiecallotRaesquuessetd 5i3n0t3w0o)-yAenaarlyrtaitcPalFOS carcinogenicity study (T-6295, Covance 6329-183). METHOD CMoentfheorde/nGcueiodnelHianremofnoilzlaotwieodn(i(.cI.C,HO)EHCarDmo4n1i4z,eedtc.T)r:ipaTrhteitereGquuiidreelmiennetsoonftDehteecItnitoenomaftiToonxailcity rtoodReenptrsopdeucciteisownefroer uMseeddicaisnathlepbraosdiusctfso,r ssttaugdeysdCesaingdnD(Uo.fS.thFeoordeparnodduDctriuvgeApdrmoicneissstriantaionno,n1994. Federal Register, September 22, 1194, Vol. 59, No. 183). rGeLguPla(ti/oNns)o:f tThhee Us.tSu.dyFwoaosd caonnddDucrtuegdAidnmicnoimsptlriaatnicoen w(iFtDhA)th,etGhoeoJdapLaanbeosreaMtionriysPtrraycotficHee(alGtLhP) daenvdiaWteilofnasrfer(oMmHthWe)GaLnPd rtehgeuElautrioopnesatnhaEtcaofnfeocmtiedc tChoemqmuualniittyyor(EinEtCe)g.ritTyohefrtehewesrteudny.o significant Year study performed: 1999 Species/Strain: New Zealand White rabbits Number of animals per dose: 22 Route of administration: Gavage wDeorseinagdmriengiistmeerned(lPsottaalslswiiutmhPuenriftlsu)o:roFooctuyrlsgurlofuopnsatoef(2P2FpOrSe)gniann0t.N5e%wTwZeeaelna-n8d0Wbhyitgeavraagbbeiotsn igensdtiavtiidounaldabyosdy7-w2e0i.ghAts.dose volumeof S ml/kg was administered, adjusted daily on the basis of Doses: 0,0.1, 1.0, 2.5, and 3.75 mg/kg/day Sctoamtipsuttiecra-lgmeenetrhaotdesd ursaendd:omTuhneitsa.niTmahleslwititler bweasastshiegnuneidtotofimnedaisvuidrueamlenhto.usiCnlginoincatlheobbsaesrivsaotfion BainndomoitahelrDpirsotrpiobruttiioonn.datCaonwteirneuoanuasldyastead(ucs.gi.n,gmtahteeVmaarliabnocdeyTweesitghftors,Hobmoodgyewneeiigthytofchtahneges, DrfeaediciolnsAumvpteiosRnepvomratleusepsneansndd Vliter averages for percent male fetuses, percent resorbedS031 cuosnicnegpBtaurstelse,tt'fsetTalesbtodofyHwoemigohgtesn,efiettaylofaVnaormiaalyncdeastaaannddthfeetaAlnaolssyisfiiscoatfiVoanrsiiatnecdea.taI)fwtehreeAannaallyysziesd oifnVdiavriidauanlcegrwouapss.siIgnfiftihceanAtn,alDyusninesotftV'sarTiesatncweaswaussendottoapipdernotpirfiyatteh,etshteatKisrtuiscaklals-iWganilfliicsanTceestofwathse uMseetd.hodIon fcasMeusl,tiipnlwehCiocmhpKarruisskoanls-WwaalsliussTeedsttowiadsensttiaftyistthiecasltlaytissitgincailfisciagnntif(ipc<a0n.c0eo),fDtuhnen's pirndoicveidduuraelsgdreosucprsi.beCdofuonrtthdeatKaroubstkaailn-eWdalaltiCsaeTessatr.ean-sectioning were evaluated using the pRreemganarnktsN-eDwetZaeiallaannddWdhiistceusrsababniytss(iogbntiafiincaendtfprroomtoCcoovlapnacreaRmeesteearrschanPrdodduecvtisa,tiIonncs.):, T2i2mpeedr- ggarovuapg,ewoenregegsitavteinondodsaeysso7f-200,.0.1A, d1o.0s,e2v5olourm3e.7o5fm5gm/lkg//kdgawyaPsFaOdSmiinnis0t.e5re%d,Twaedjeuns-t8e0d dbayily on the basis of individual body weights. clinical observations were recorded 1 hTohuerdporeiosrwteoraenodbasfetrrveddostiwnigcedudariilnyg ftohre vtiraebialtimteyn,tapnedriod awenidgohntscewedarielyredcuorridnegdtohne pgoesstt-attrioenatdmaeynst p0earniodd6(-i2.9c.;gfeosotdatcioonnsduamypst2i0o-n29w).asMraetceorrndaeld bdaoidlyy tthhorroaucgich,ouatbdtohemisntuadly.anOdnpeglevsitcatviiosncedraayw2a9s, ctohnedduocetsedwearnedctuhtehannizued;moafbgcrooerspsornreacrloutpesayoifn tcahceh oanvdardyeawdasferteucsoersd,eadn.dTeharelyutaernidwlearteereexsoarmpitnioendsf.orThneufmetbusaeensrdwedriestwreibiugthieodn,ofsiemxpeldanatnadtieoxnasm,inlievde `faonrdetxhteerbnraalinaobfnoromnaleit-iehso.afltAhlfel ffeettuusseess wweerree efxreaem-ihnaendd cfrorosvsi-ssceecrtailoannedd asknedleetxaalmaibnneodrmianlistitiue.s RESULTS N`TOheANEOLAE---Lmaftorerdnevaellaopnmdendteavleltoopxmiceinttyails:1T.0hemgN/kOgA/dEaLy.for maternal toxicity is 0.1 mg/kg/day. iLs O1.A0EmLg/k(gdo/sdeaya,nbdaesefdfeocnt-a)bomrattieornsn,alinacniddendceevseolfospcmaennttafle:cesT,haendLdOeAcrEeLasfeosrimnabtoedmyalwetiogxhictity graeidnusctainodnsfionodbocdoynswuemipgthitona.ndTihnecrLeaOsAedEiLncfiodrednecveselionpfmeetnaltaalltteorxatiicointsy.is 2.5 mg/kg/day, based on `cToonxsiicstreedsopfotnhsee/effoflelcowtisnbg:y adboosretiloenvselat- m2a.5temrgn/aklg:/dMaaytaenmdalabtoovxeicoictycuwrarsinegvoidneGntDat2a2l-l2d8;oses and increased `gain at all incidenceofscant doses; reductions ifnecfeosodatcaollnsduomsepst;iornedautct2i.5onmsgi/nkmge/daanybaonddyawbeoiveg.ht and body weight d`oTosxeiscorefsp2o.5nmsge//ekfgf/edcatys banyddaobsoevleevaenld-codnesviesltoepdomfetnthael:foDlleovweilnog:pmernetdaulcttiooxnisciitnymweaasnevfeitdaelnbtoadty weight at 2.5 mg/kg/day and above; delayed ossification at 2.5 mg/kg/day and above. Statistical results: Of nia scone Report Append --_-- Co az 000320 IMnactiedrennaclesdoatfa:scSatnattifsetciecsalalty 3s.i7g5nimfigc/akngt/idnacyreraeseaschiendasbtoarttisitoincsalwseirgeniofbiscearncveed(pa<t03..0715).mgD/oksga/dgaey-. dtheepe1n.d0,en2t.,5,saignndif3i.c7a5ntmbgo/dkgy/wdeaiyghdtosraegdeucgtrioounspsorfobrotdhye wenetiigrhetdloossasgees p(epr<i0o.d05(ocra0lc.u0l1at)edocaesuGrrDed7-in 2d1o)s.agDeosgraoguep-sdefpoerntdheenetntrierdeupcetriioondsoifngbeosdtaytwieoing(htGDga0i-n2s9o)cacnudrefodr itnhethgees2t.a5tiaonndp3e.r7i5odmgaf/tkegr/tdhea.y Ainvietriaatgioenobfoddoyswieniggh(tsGDwe7r-e29s;igsniigfniicfainctalnyt raetdpu<c0e.d01(pi<n0.th0e52o.r50m.g0/1)kgo/ndaGyDdo1s7a-g2e4girnoutph)e.3.75 ming/thkeg/2d.5ayanddos3a.g7e5 gmrgo/ukpg./dFaeyeddocsoangseumgprtouiposn fvoarlutehse wenetrieresdigonsiafgiecapnetlryiorded(uGcDed7-(2p1<)0,.0a5ndorth0e.01) entire period after the initiationofdosage (GD 7-29). PFe=ta0l.0d1a,tar:esFpeetcatlivebloyd)yinwetihegh2t.s75(taotnadl,3m.a7l5edoasnadgfeegmraoluep)s.werSeigsniigfniicfainctandtellyayrsed(upc<e0d.0(5p<a0n.d050.a0n1d) in litter groups. and fetal averages for ossification were seen at both 2.5 and 3.75 mg/kg/day dosage Remarks -- Additional information to adequately assess the data: Maternal toxicity mg/kg/day group was and evident at nine does idnotshees3o.f751.m0gm/gk/gk/gd/adyaayboarntdeda.bovAel.l One doe abortions in the 2.5 occurred on gsiegsntiaftiicoanntdaiynscr2e2a-se28inatnhdewienrceidceonncseiodfesrceadnttrefaetcmeesnti.nrtehleat3e.d75bymgt/hekgs/tduadyy agurtohuopr.s.ScTahnetrefewcaess a mwaetreemaallsobnoodtyedweiingohntegaanidnstwhreereedsoicgsniifnictahnetl1y.0readnudc2e.d5imngt/hkeg3/.d7a5ymggr/okugp/s,daryesgpreoctuipveolny.gesMteaatinon dtraeyastm1e0n-t13p,er1i3o-d16(,da1y6s-179-2a1)n,d p2o1s-t2-4t.reMatemaenntbpoedryiowde(idgahytsg2a1i-n2s9w)earnedadlusoractailocnuolfatthedefsotrutdhye (days p7e-2r9i)o.d iTnhethree 1w.a0,s2a.5siagnndif3ic.a7n5tmrge/dkucgt/idoanyignrmouepas.n mMaetearnnablobdoydwyeiwgehigthgtaignaifnordutrhienegnttihreetsrteuadtyment (p&e/rkigo/ddwaya)s waalssossiiggnniiffiiccaannttllyyrreedduucceeddiinnttheh2e.52.5 mmgg//kkgg//ddaayyggrroouupp.onMgeeastnatfiooonddcaoynssu16m-p1t9i,on19-21 and 21-24, as well as significantly reduced for the entire study period (days in the 3.75 mg/kg/day group on g7e-s2t9a).tioMn edaaynsfo13o-d16c,on1s6u-m19p,ti1o9n-2w1asand 21- 2(48,6.a4s%)w,el1l7as(7t7h.e3%en)t,iraentdr2e1at(m9en5t.4p%er)iorda.bbiPtrseignneaancchydoocscaugreregdroiunp.20 C(e9a0s%a)r,ea1n9-s(e8c6t.i4o%n)i,ng19 observations on GD 29 were respective dosage groups. based on 20, 18, 19, 16, and 12 pregnant rabbits in cachofthe five cDoervpeolroapmluetneta,alretsooxripctiitoynsw,alsievev/iddeeandt fatetdusoesse,solfit2te.r5simzeg/akngd/sdeaxyraantidoawbeorvee.coTmhpearnaubmlbeearmoonfg. tsriegantiefdicaanntdlycornetdruoclegdroiunpts.he 2M.e5aanndfe3t.al75bomdgy/kwge/idgahytg(rmoaulpes,.feTmhaelreeawnadssaelxseosacsoimgbniinfiecda)ntwas rgreoduupcst,ioannidn athseigonsisfiifciacnattiroendoufcttihoensintethmeuomss(ilfiitceartaivoenroafgtehse) hinyothied2.(l5itaenrdav3e.r7a5gemsg)/,kmge/tdaacyarpal 1li0t5tesreaxvteerrangale,s)soafntdtipsusbuiesalnidtesrkealentdalfeatlatlearvateiroangses()mailnftohrema3t.i7o5nmsga/nkdg/vdaraiyatgiroonusp). weOrtehecronfseitadlered Draft InitialAssessmReepnortt- Appendic viz 000321 ------------------ ean CS huinsrteolraitceald tcoonttrreoaltrmaenngte.because the incidences were not dosage-dependent and/or were within CONCLUSIONS Caboomvmeeanndttohnisaruetvhioerw'esrcagornecelsu.sions and whether you agree: Conclusions are summarized REFERENCE P1r9o9v9.ideArfuglulsciRteasteiaorncohfLsatbuordaytorreiveise,wIendc.: PCrhortiosctioalnN,uMm.bSe.r,:Ho4b1e8-r0m1a2n,,JAanMu.a,ryan1d99Y9.ork",OrRaGl. (Stomach Tube) Developmental Toxicity StudyofPFOS in Rabbits". OTHER None of nia Assos Report Appedic ---------------------------- $603z22 ROBUST SUMMARY - R45 Title: Oral Teratology StudyofFC-95 in Rats - Experiment No. 0680TR0008 TEST SUBSTANCE Identity: Potassium Perfluorooctylsulfonate, CAS No. 2795-393 uRneimfaorrmkist:y, cTeosmtpoasnidt/ioornc,opnutrriotlyaortrioctlehecrhaprearcttienreinztacthiaornafcotrerFiCz-a9ti5o,nsLooftt6h4e0.tesTthaenidd/eonrtictoyntsrtorlength, substances were determined and documented asof May 8, 1950. METHOD sMpeetchifoide/dGbuuitdealppienaersfotlolboewesdim(iilca.r, OECD 414, ete): in design to OECD Actual 414. guideline followed was not JGaLnuPar(yY,/N1)9:66T(h"eGupirdoecleidnuersefcoromRpelpireosduwcittihotnheStguednieersalforreScaofmemteynEdvaatliuoantisoonfotfheDrFuDgsA fiosrsHueudmiann aUnsed"S)a.feTthyeEsvtaulduyatwiaosn Lcaobnodruacttoerdy'asccSotradnidnagrdtoOtpheera1t9i7n8g GPoroocdedLuraebso.ratory Practice regulations Year study performed: 1980 Species/Strain: Sprague-Dawley rats Numberof animals per dose: 22 Route of administration: Gavage aDdomsiinnigstreeregdimpeonta(slissituamllpewriftlhuournoiotcst):ylsFuolufrongartoeuipnsocfom22oitlibmye-gmaavtaegdeSopnragegsutea-tDioanwldeayysra6t-s1w5ere Doses were adjusted according to the most recent recorded body weight. Doses: 0,1,5,and 10 mg/kg/day gSetanteirsattiecdalrmaentdhoomdnsuumsbeedr:s tTahblee.anTimhaelsstwateirsteicaaslsmiegtnehdodcsagteosbaeccuosreddinfogrtaonaalcyosimspuotfetrh-e data are: Dunnett's t test of implantation for dam and pup sites and number woefigchotrsp,ornaulmubteear;oCfhfietsuqsueasr,enfuomrbpeerrcoefnrtesaobrnportmiaolnitsiitcess., number PRoetmaasrsikusm--peDreftlauiolroaoncdtydlsiuslcfuosnsaatenywsaisgnaidfmiicnainsttperroetdoicnolcopmaroaimlebtyergsavaangde tdoevfioautriognrso:ups of 22 time-mated Sprague-Dawley rats weighing 175-261, at dosesof0, 1, 5, and 10 mg/kg/day DcPoFrnOsItnStainotntdsdosasmyeesnv6so-lR1uo5mroefoAgpefpsetmantdli/okng(oGforbtonedry,w1e9i8g0h)t. aTndheobasneirmvaelds wdaeirley dforsoemddaacyco3rtdhirnoguagthaday 20 Vino ---------------- CS 000323 oafngdes2t0aotfigoenstfaortiaobnnoarnmdatlheclriantis.calAslilgnasn.imBalosdywewreeigshatcrsiwfiecreed roencodradyed20onbydacyersvi3,ca6l,d9i,sl1o2c,at15i,on avinadblteheaonvdarnioens-,viutaebrlieafnedtucsoens,tenntsuwermoeferbxeasomeripnteirdonfosrittehse, nanudmbneurmobfecroropfiomrpalalnutteaat,inounmsbiteers of Ftheitrudsoesf wtheerefewtuesiegshweedraenfdixseedxeidn Baonudinsu'bsjescotluetditoon eaxntderenxaalmgirnoesds nfeocrrvoipsscye.ralApabpnroorxmiamlaitteielsyboyne- free-hand sectioning. alizarin red. The remaining fetuses were subjected to a skeletal examination using RESULTS NOAEL indicated. -maternal A NOAEL and developmental: A NOAEL for developmental toxicity could onof5t bmeg/esktga/bdlaiyshefodrwmhaetenrlneanlsteofxfieccittsyawracs considered. Iflens effects are considered an artifact, there is a NOAEL of 10 mg/kg. LmaOteArEnaLl (todxoisceitaynwdaseifndifc-atemedactbeatrsned)alonansidgndiefviecalnotprmeednutcatli:onsAinLOmeAaEnLboofdy10wemigg/hktgs/dduaryinfogr gtoexsitcaittiyonwadsayno1t2-e2s0taabtlitshheehdiagsh-hdioghseesgtrdoouspeoftes1t0edmgw/aksg/adaNyO.AEAL,LOAEL for developmental Toxic during responseeffects GD 12-20 at the bhiygdh-odsoesleegverlou-pmoafte1r0namlg:/kSgi/gdnaiyf.icant reductions in mean body weights d`eTovxeileopremsepnotnasle/veafrfieatcitosnbsyanddosaebnloervmeall-itdieevseolfotphmeenlteanlso:fUtnhueseuyaellwyehriegohbisnecrivdeednciensalolfdose groups. cSotnattirsotlisca(lDruensnulettst: tMesetapn<ma0t.e05r)n.al body weights were statistically significantly lower than Mean litter p<0.05). data and pup weights were not significantly different from controls (Dunnett'sttest Number p<0.05). of fetuses with gross findings were not significantly different from controls (Chi-square Number controls and percent (Chi-square of fetuses p<0.05). with skeleton findings were not significantly different from sNeucmobnedarryanldenpseracbeenrtraotfiofnestuwseersewistighniinftiecrannatllyfihnidgihnegrst-ha-ndecvonetlrooplmse(nCthail-slqeunsaraebnpo<r0m.a0l5i)t.ies with cRoenmsiasrtkedsof--sAidgdniiftiicoannatl riendfuocrtimoantsioinn mteoaandebqoudaytweeliygahstssedsusrtihnegdGatDa:12S-i2g0nsatofthmeahtiegmha-ldotsoexicity gtorxoiucpitoyfev1i0dmegn/tkagt/ddoays.es oNfo1o0thmegr/ksigg/ndsaoyfcmoantseirsntaedlotforxeicdiutcytwioenrse irneptohretemde.anDenvuemlboepmreonftal ainmdpltaonttaaltfieotnusseiste,s,buctorthpeordaiflfueterae,ncreessowreprteionnostitsetsatainstdictahlelymseiagnnifnicuamnbte. rsInoafddviitaibolne,muanlues,ufaelmlaylhei,gh iL ncidencesy of unossifie--d, a--ssymetrical, bipartite, and missing sternebrae were observedvainnall 000324 rdaotseeagnrdoutphser;ehfoorweevweerr,etnhoetsecosnkseiledtearledvatroiabteiotnrseawtemrenet-arlesloaotbeds.erTvehdeimnocsotntnrootlabfleetussiegsnatofthe same ydeev,elwohpimcehntwaalstnooxticsieteynobinsecrovnterdolisn. alTlhdeosperogproorutpisoncoofnsfiesttuesdesofwiabtnhotrhmeallietniseasobnfortmheallietnysoifn othnee. boreblootcahllizeendsetsowtahse asrieganioffictahnetleymhbirgyhoenrailnltehneshniugchleduoss,eaglrtohuopu.ghAallvaeryieetaybnoofrmmoarlpihtoielsogaipcpaelared to aappppeeaarreandcteosbweearne aprrreessetntinwdietvhienlotphamtenlotcoafttihone. pArcicmoarrdyilnegnstofitbheersauftohromrsi,ngthtihseaebmnborrmyaolniatlylens snuucrlreouusn.diSnegctohnedaabrnyolremnaslfiebmebrrdyeovneallopnumcelnetusp.roAgrnesasmeednndomremnatlltyo etxhceerpetsuilmtmseadnidatdeilsycussion sseeccttiioonnicnognacnldudtehde trhaantgtehoefggrroossssflienndsinogbsoefravalteinosncsleafntdwtahseadnifafretriefnacctescraemaotendgbtyhefrdeoesheangdroup finrceicdheanncdessewcetiroenidnugeatnodthtehemlainmniteartiaonnds ifnrheeqrueenntcyinivniwsuhailcihzitnhgetlheensemcblreyfoanratilfancutclweauss,creAated by subsequent study was not able to repeat this finding. CONCLUSIONS cChoemmimceanlltyornelaatuetdhobra'ssedcoonnclsuusbisoenqsueanntdstwuhdeietsh.eAr ysouummagarreyeo:ftThhee lleennssdiesfseucetiinstnhoetRcioknesridered GLoarbtonreart,ordiaetsedisNcoovnteamibneedri6n, a19m8e1m.orandum to the file written by the Study Director, EG REFERENCE RPirkoevridLeabfourlaltcoirtiaetsi,onInoc.f sEtxupdeyrirmeevnitewNeudm:bGeorr:t0er6,80ET.RG0.010988,0.DeScaefmebtyerE,va1l9u8a0t.io"nOLraabloTreartaotroylaongyd Study ofFC-95 in Rats". DGaotret"n,er3pEpG,.NMoevemmobetor Study Files 6, 1981. titled "Fetal Rat Lens Artifact - Summaryof Developments to OTHER Any other information deemed appropriate: None rat nie sscssmens Report Append "$b0azs ROBUST SUMMARY - RS46 TITLE: Rat Teratology Study T-3351 Final Report ~ Project No. 154-160 (Hazelton 1983) TEST SUBSTANCE Identity: Potassium Perfluorooctylsulfonate, CAS No. 2795-393 Remarks: sponsoron The test January material, T-3351 (Lot No. 5, 1983 and was stored at r8o0o2m75t)e,mpaerwahtiutree.powTdheer,teswtamsatreercieailvewdasfraosmstuhmeed to on bceom1p0os0i%tiaocnt,ivoercootmhpeorucnhda.ractIenrfiosrtimcastiwohniocnh the methodof define the test synthesis, stability, as wellas material, are on file with the data sponsor. METHOD sMpeetchifoide/dGbuuitdaeplpienaersfotlolboewesdim(iil.ca.r, OECD 414, in design to etc.): Actual OECD414. guideline followed was not cGoLndPuc(tYe/dN)a:ccQouradliintgytAostshuersatnacnedairndspoepcetriaotnisnogfpthreocesdtuurdeysaonfdtrheevOifefwiocfetohfeQufianlailtryeAposrsturwaenrcee and iascscuoerddionngDteoctehembgeenrer22a,l r1e9q7u8i,rbeymetnhtesoFfootdheanGdooDdruLgabAodrmaitnoirsytrPartaicotnicfeorrecgoumlpaltiioannscethaotnwaenrdeafter June 20,1979, Year study performed: 1983 Species/Strain: Sprague-Dawley rats Numberof animals per dose: 25 Route of administration: Gavage aDdomsiinnigstreergedimpeonta(slissituamllpewriftlhuournoiotest):ylsFuolufrongartoeuipnscoofm25oiplrbeygngaanvtaSgperoangugees-tDaatwiloneydaryatss6w-e1r5e. Doses were adjusted according to the most recent recorded body weight. Doses: 0, 1, 5, and 10 mg/kg/day Statistical control vs. cmoemtphooudnsd-utsreeda:teSdtagtrisotuipcamlemaenthcoodmspaursiesdonfso.r analysis of the data:Dunnett's { If the variances were proved to test be. for Mhoemaongefenteaolubso,dythweediagthatswepreer alintatlerysweedrebystoatnies-tiwcaalylyclaansasliyfisceadtiaosnfaonlalloywssi:soBfarvtalretita'nsctees(tAfNorOVA). IhFoAmoNgCenOeVitAyowfasvasriigannicfiecsanwta,scopnetrrfoolrvmse. dtbreyaotnmeen-twgaryoculpascsoifmipcaartiiosnoonfscwoevraeriaannacleys(eAd NuCsOinVgAt)h.e rfGoaarfmhenosimaoagnresdneseHsimoetwnyseolReflpovrmatordiAiapfnpiceceiaste,iYoAnoNfOtVhAe,TuankdeyA-NKrCaOmeVrAhowneersetleyvasliugnaitfeidcaantttdhief5fe%reonncee-tteasit.ledTests van 000326 pervoablaubaitleidtyatletvheel.5%Cotnwtor-otlaivlse.dcopmrpoboaubnidl-ittryelaetveeld. gPreorucpenmteafentaclovmipabairliitsyo,npseorfcetnhtefaebtaolvelodsast(adewearde. waenrdereasnoarlbyisnegdfbeytunseosn)p,aprearmceetnrticeaorlnye,-lwaatey, AanNdOtoVtaAl arensdortphteioTnesr,psatnrda-thJeonncukmhebeerreotfesdtefaodr ftreetnuds,es `The liter Amnitage was test used as the experimental unit. for linear trend in proportions. TIefraastioglnoigfyicdaanttatwreenrdewaansalnyosteedd,ustihnegretshueltCsocohfran- oFbissheerrv'esd,"eoxriafctthteerset wwaesreaesviaglnuiafitceadntatttrheendonwei-tthaisleevde,r5e%depleavrelt.ureIffarosimgniti,ftihceanrtesturletnsdowfaFissnhoetr's "exact" test were evaluated at the two-tailed, 5% level, RPoetmasasriukms~peDreftlauiolroaoncdtydlissulcfuosnsaatenywassigandimfiicnainstteprreodtoicnoclopmaroialmebtyegrasvaagnedtdoevfioautrigornso:ups of 25 p(rGeDg)na6n-t15Sp(rWaegzueel-,Da1w98l3e)y.raStesxautaldloysemsaotfu0r,e S1,pr5,agauned-1D0awmlge/ykgra/tds,ayonPeFpOeSr osenxgpeesrtactaigoen,dwaeyrse dpaaiilryedvaugntiinlalcoenxfaimrimnaattiioonnosffmoarttihnegproersuenntcile tawnod wvieaebkilsithyaodfeslpapesremd.orMtahteipnrgesweanscecoonfafircmoepdulbaytory oplfu3g.mIT/hkegodfabyoodfycownefiigrhmtatwiaosnoafdmmiantiisntgerweadsanddesdiogsneastewdearsedaadyju0stoefdgeasctcaotridoinn.g Atodtohseemovsotlume mroercteanltliytyreacnodrmdeodribboudnydiwteyigahntd moenacseudraeimleyntfsor.clDinaimcasl wsiegrnesoofbsteorxivceidtyt.wiIcnedidvaiildyuaflorbsoidgynswoefights aGnDd 2fo0obdycConOs;umasppthiyoxniawteiroen raencdortdheedfeotnusGesDw6e,re8,d1e2l,iv1e6r,eadnbdy2c0.esaArneiamnaslesctwieorneonsaGcrDifi2c0e,d oAn garnodsesxnaemcirnoepdsyfowrasthpeenrufmobrmeerdaonnd apllladcaemmse.ntTohfeimutpelraunstaftrioomn seiatcesh, fneummableerwaansdeoxfcliisvede,awnedidgehaedd tfheetucsoens,tennutmsbweerreofrecmarolvyeda.ndTlhatee orveasorripetsiownesr,eaenxdaamniyneadbnfoorrmatlhietniuesmbaenrdotfhecnorwpeoirgahleudteaag.aiEnacafhter efxetmeamlaellwya.s Aepxparmoixniemdabteylgyroosnes-ntehcirrodopsfy.theEafcethusfeestuwsewraesfsixeexdedi,nwBeoiugihne'ds,saonludtieoxnamainndeedxamined afonrdvbirsacienr.alTahbenorremmaaliitniiensg bfyettuhseesWwielrseonsutbejcehcntieqduet,owaistkhelpeatratliceuxlaamriantatetnitoinonthtaottihnecleuydeesd,.palate, epevlavliucatgiiorndolefs tuhseinskgulall,izlaroinng rbeodn;ebs,onveeratleibrganlmecnotluamnnd,dreigbrceaeogef,oesxstirfeimciattiieosn, waenrdepeacltsooreavlalaunadted. RESULTS NThOeANEOLAE--Lmaftorerdnevaellaonpmdednteavleltoopxmiceinttyails:1 The NOAEL mg/kg/day. for matemal toxicity is | mg/kg/day. LbaOseAdEoLn -climnaitcaelrnsiaglnsanofdtdoexviceiltoy,pmdeenctreaals:esTihnebLodOyAwEeLigfhotramnadtefmoaodl ctooxniscuimtpytiiso5n,mgd/ekcgr/edaaseys, in uterine weights, and an increased incidence in gastrointestinal lesions. The and LOAEL increases for in edxetveemlaolpmaenndtavlistcoexriacliatynoimsa5limegs/kagn/ddavyar,iabtaisonesd. on decreased fetal body weight Toxic response/effects by dose level - maternal: Clinical signsoftoxicity, decreases in body Or nilAssmRaepanrs- ppends van 000327 ee weights and food consumption at 5 and 10 mg/kg/day; decreases in uterine weights, increased incidence in gastrointestinal lesions, and two deaths at 10 mg/kg/day. `Toxic response/effects by dose level - developmental: Decreased fetal weight at 5 and 10 mg/kg/day; external and visceral anomalies and skeletal variations at 10 mg/kg/day. Statistical results: Statistically significant differences between controls and treated were noted for the following matemal endpoints: mean body weight gain, mean total food consumption, and mean gravid uterine weight. Nonparametric analysisofthe mean incidence of late resorptions, total resorptions, number ofdead fetuses, and fetal loss did not indicate statistical significance; however, there was a significant linear trend towards an increased incidence in these data with respect to control. The primary trend component was contributed by the highdose group. ~ Statistically significant treatment-related increases in the incidences of visceral anomalies and skeletal variants were also observed. Remarks -- Additional information to adequately assess the data: Evidenceofmatemal toxicity, that was observed at the and 10 mg/kg/day dose groups both during and following treatment and considered to be treatment-related, consistedof hunched posture, anorexia, bloody vaginal discharge, uterine stains, alopecia, rough hair coat, and bloody crust. Significant decreases in mean body weight gains during GD 6-8, 6-16, and 0-20 were also observed at the 5 and 10 mg/kg/day dose groups. These reductions were considered to be treatment-related since mean body weight gains were greater than controlsduring the post-exposure period (GD 16-20). Significant decreases in mean total food consumption were observed on GD 17-20 in thel0 mg/kg/day dose group, and on GD 7-16 and 0-20 in both the 5 and 10 mg/kg/day dose groups. `The mean gravid uterine weight in the 10 mg/kg/day dose group was significantly lower when compared with controls. The mean terminal body weights minus the gravid uterine weights were lower in all treated groups, with significant decreases at 5 and 10 mg/kg/day. High-dose animals also exhibited an increased incidence in gastrointestinal lesions. No significant differences were observed in pregnancy rates, numberofcorpora lutea, and number and placementof implantation sites among treated and control groups. Two dams in the 10 mg/kg/day dose group were found dead on GD 17, Signs of developmental toxicity included a dose-related trend toward an increased incidence of late resorpions, total resorptions, numberofdead fetuses, and fetal loss, although, none of these effects were statistically significantly different from controls. Significant decreases in mean fetal weights for both males and females were observed in the 5 and 10 mg/kg/day dose groups. The percentofmale fetuses was 52%, 54%, and 60% for 1, 5, and 10 mg/kg/day, respectively, compared to 44% in controls. Statistically significant increases in the incidences in the number oflitters containing fetuses with visceral anomalies, delayed ossification, and skeletal variationswere observed in the high dose group of 10 mg/kg/day. These included extemal and visceral anomaliesofthe cleft palate, subcutaneous edema, and cryplorchidism as well as delays in skeletal ossificationof the skull, pectoral girdle, rib cage, vertebral column, pelvic girdle and limbs. Skeletal variations in the ribs and stemebrae were also observed. rat nial sessmens Report Append vax 000328 CONCLUSIONS Comment on author's conclusions and whether you agree: The developmental eye abnormalities that were seen in Gortner (1980) were not observed in the present developmental toxicity study even though the study design and doses were the same. REFERENCE Wetzel, LT. 1983. Hazelton Laboratories America, Inc. Project Number: 154-160, December 19,1983. "Rat Teratology Study, T-3351, Final Report". OTHER None Draft Initial AssessmentReport- Appendix V va 000329 ROBUST SUMMARY- RS47 Title: COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS -- ARGUS RESEARCH LABORATORIES STUDY NUMBER: 6295.9, 1999.Protocol 418-008 TEST SUBSTANCE Identity: Potassium Perflurooctylsulfonate (PFOS), CAS No. 2795-39-3. Remarks: The test article, FC-95 (lot 217) was received on May 20, 1998, and stored at room temperature. Prepared suspensions were stored at room temperature overnight. Information regarding the purity, identity, strength and compositionofthe test article is on file with the Sponsor. METHOD Method/Guideline followed: This study was designed to evaluate ICH Harmonized Tripartite Guideline stages A-F. A modificationof the requirements of the U.S. Food and Drug Administration (FDA) were used as a basis for the study design. Type of study: Two-generation reproductive toxicity GLP (Y/N): Yes. The study was conducted in compliance with the Good Laboratory Practice: (GLP) Regulations of the U.S. Food and Drug Administration (FDA), the Japanese Ministry of Health and Welfare (MHW) and the European Economic Community (EEC). There were no significant deviations from the GLP regulations that affected the quality or integrityofthe study. Quality Assurance Unit findings derived from the inspections during the conductofthis study `were documented. Year study performed: 1999 Species/Strain: Rat Crl:CDBR VAF Plus (Sprague-Dawley) Sex (males/females/both): Both Numberof animals per dose: F, = 35. Twenty-five females for full evaluationofF,generation; 10 females for determinationofreproductive status at DG 10. F, had 25 each sex, per dose. Route of administration: Oral (gavage) Dosing regimen: Five groupsof 35 rats per sex per dose group were administered PFOS by `gavage for six weeks prior to cohabitation and during 14 daysofmating. Treatment in Fymale rats continued until one day before sacrifice (approximately 63 days total); female rats were treated daily throughout gestation, parturition, and lactation. F1 rats selected for mating and rearingofthe F2 generation received daily (gavage) dosesofPFOS at 22 days ofage and thereafter. ratntlsesRepsort Appeic $60330 Doses: 0,0.1, 04, 1.6, and 3.2 mg/kg/day Premating exposure direct dosing starting period at day for males/females: continuing until LD Six weeks foPr 21 of F, liters. (E,); in utero and lactation, SHtoamtoigsteinceailtmyeotfhtohdesBuisneodm:iaPlroDipsotrrtiibountidoant.a Cwoenrteiannuaoluyszdeadtuas(ibnogdtyhweeViaghrtisa,ncbeodTyeswteifgorht changes and feed consumption) were analyzed using Bartlett's Testof Homogeneity of Variance and Analysisof Variance (ANOVA). If the ANOVA was significant (p < 0.05), Dunnett's Test was usedto identify the statistical significanceof the individual groups. If the ANOVA was not appropriate, the Kruskal-Wallis Test was used. In cases where the Kruskal`Wallis Test was statistically significant (p < 0.05), Dunn's Method of Multiple Comparisons was used to identify the statistical significanceofthe individual groups.If there were greater than 75% tes, Fisher's Exact Test was used. Fishers Exact Test was also used to evaluate necropsy data for the pups that were stillborn or found dead. Data obtained at Ceasarcansectioning, natural delivery, preweaning reflex/physical developmental data and postweaning behavorial data involving discrete data (numberof corpora lutea, numberofpups per liter, trials toa criterion) were evaluated by the Kruskal-Wallis Test. Remarks~ Detail and discuss any significant protocol parameters and deviations: Sce Table [Schema on page 1-4ofthe Report to be reproduced] for schematic description of study. F, Generation: Parental animals (F,) were observed twice daily for clinical signs. Body weights and food consumption values were recorded weekly during the treatment period in male rats; and weekly during mating and then daily during gestation, and on lactation days 1, 4,7, 10, 14, and at sacrifice in female rats. Each dosage group consistedof two sets of female rats. One set consisted ofthe first ten female rats with confirmationofmating that were dosed until gestation day (GD) 10, sacrificed, and necropsicd to determine the number of corpora lutea, implantations, and number of viable and non-viable embryos. The remaining females comprised the second set, which delivered naturally. After the 21day gestation period, the dams were evaluated for clinical signs during parturition and length of gestation. During parturition each litter was evaluated at least twice daily for size and pup viability at birth. Pup observations during the 21-day lactation period included physical signs, body weights, nursing behavior, surface righting reflex, pinna unfolding, eye opening, acoustic startle response and air righting reflex. Pupil constriction was evaluated only on lactation day 21. On lactation day 4, litters were randomly culled to four male and four female pups. The remaining pups were sacrificed and necropsied. `The F, male rats were sacrificed and necropsied after the end of dosing at the timeofparturition (lactation day 1). The testes, epididymides, prostate, and seminal vesicles were weighed. Evaluationsofsperm number, motility, and morphology were not included in the rat nial sos Report Appeic va 000331 protocol. `The F, generation females that delivered naturally were sacrificed on lactation day (LD) 21 and necropsied. Ovaries were examined as above and the number and distributionof implantation sites was recorded. The liver from each parental rat was removed, weighed and analyzed. Blood samples were collected from male rats that had mated and from female rats on LD 21 for pharmacokinetic analysis; livers from the pups from the litters of these five dams were also collected for analysis. `The final resultsofthese analyses were not available at the timeof this review. F, Generation: Since F, generation pup viability was significantly reduced in the 1.6 and 3.2 mg/kg/day dosages groups, only the 0.1 and 0.4 mg/kg/day dosage groups were carried into the second generation. `Twenty-five F, generation rats per sex per dose group were administered PFOS by gavage at dosesof 0, 0.1, and 0.4 mg/kg/day beginning on LD 22 and continuing through the day before sacrifice. At 24 daysofage, one rat per sex per liter in each dosage group was tested in a passive avoidance paradigm. On LD 28, female evaluations commenced to determine the age of vaginal patency and on LD 34, male rat evaluation commenced to determine the ageofpreputial separation. One rat per sex perlitterwas evaluated in a water-filled M-maze on LD 70. Assignment to cohabitation within each dosage group began on LD 90. Females with evidence of mating were considered to be at GD 0 and assigned to individual housing for the remainder of the dosing period. The F, generation male rats were sacrificed after mating necropsied and evaluated as described in the FO generation. All F, generation females were allowed to deliver naturally and raise liters until LD 21. Dams that delivered liters were sacrificed and necropsied onLD 21. All, generation pups were sacrificed, necropsied, and examined on LD 21 as previously described for the F, generation pups. RESULTS `The results incorporate the findingsofthe original report and Final Report AmendmentI dated 13 April, 2000 submitted by the study director (RG York) and cosigned by the quality assurance `manager (NJ Gongliewski). NOAEL for F,, F,, and F,: The NOAEL for the , generation males and females = 0.1 mg/kg/day, the lowest dose tested. The NOAEL for the F, generation = 0.4 mg/kg/day, the highest dose tested. The NOAEL for the F, generation = 0.4 mg/kg/day, the highest dose tested. , LOAEL (dose and effect) ~ for F., F,, and F,: The LOAEL for the F, generation males and females = 0.4 mg/kg/day, based on reductions in body weight gain and food consumption. The LOAEL for the F, generation = 1.6 mg/kg/day, based on significant reductions in the number of implantation sites, litter size, pup viability, growth and survival. A LOAEL for the F, generation was not established as 0.4 mg/kg/day, the highest dose tested, was the NOAEL. Toxic response/effects by dose level and generation: Dra ntlAsset Ror ppendic % Vaasg 000332 F, /F,. In F, generation rats reductions in both body weight gains and in absolute and relative food consumption occurred at the 1.6 and 3.2 mg/kg/day dosage groups during the pre-mating, period. Following mating, food consumption was significantly reduced in the 0.4. And 1.6 mg/kg/day dosage groups. Terminal body weights were also significantly reduced in the 1.6 and 3.2 mg/kg/day dose groups. There was no reproductive toxicity in the F, generation mals. `While significant reductions in the absolute weights of the seminal vesicles (with fluid) and the prostate were seen at the highest dose groupof3.2 mg/kg/day organ to body weight ratios were not significantly different from controls.. A significant increase in the number of males with brown liver at 3.2 mg/kg/day dose group was reported. `The only findings reported in the F, dams occurred in the 0.4, 1.6, and 3.2 mg/kg/day dosage `groups and included localized alopecia during pre-mating, gestation, and lactation; and reductions in body weight and food consumption values observed during the pre-mating period and continuing throughout gestation and lactation. Significant reductions (p < 0.01) in gestation length, implantation sites, and liter size were observed at 3.2 mg/kg/day. Interestingly, reduction in implantation sites was not seen in the 10 rats sacrificed at DG 10. In F, males; the only reported effects were significant reductions in absolute food consumption on postweaning days 1-8 occurring at the 0.1 and 0.4 mg/kg/day dose levels. F, females; observations at the 0.4 mg/kg/day dosage group included, reductions in body weights on day 1 postweaning, significant losses in body weight on LDs 1-4, and significant reductions in food consumption on days 1-8 postweaning and during lactation. FF; Gestation length was significantly reduced at 3.2 mg/kg/day. Significant reduction in the number of implantation sites followed by a concomitant reduction in liter size was observed at 3.2 mg/kg/say. Other adverse signs in the 3.2 mg/kg/day dose level associated with reductions in pup viability and maternal care included liters with pups that were not nursing or who had no evidence of milk in the stomach, as well as maternal cannibalization of pups that were stillborn or found dead. Toxic effects in the F, generation pups consistedofreduced pup viability at the two highest dose groups (1.6 and 3.2 mg/kg/day). In the 3.2 mg/kg/day dose group 45% (71/156) of the pups were found dead on LDI; no pups survived beyond LD 4. In the 1.6 mg/kg/day dose `group, 10.6% (27/254)ofpups were dead on LD1; and an additional 26% (59/227 died between LD 2-4. Viability and lactation indices were significantly reduced in these same dosage groups (viability index = 0% at 3.2 mg/kg/day and 66% at 1.6 mg/kg/day; lactation index = 94.6% at 1.6 mg/kg/day). Statistically significant reductions in pup body weights were also observed at the two highest dosage groups. "Toxic effects in the F, generation pups consistedoftransient reductions in mean pup body weights (on aper liter basis) observed at 0.1 mg/kg/day on LD 4 and 7. At 0.4 mg/kg/day, statistically significant reductions in mean pup body weights were observed on LDs 7-14. Statistical results: F, generation male animals: Significant reductions (p < 0.05 or p< 0.01) in body weight gains at 0.4 mg/kg/day and higher. Absolute and relative food consumption values were significantly reduced (p< 0.05 or p< 0.01) in the 1.6 and 3.2 mg/kg/day dosage groups. A significant increase (p < 0.01) in the number ofmale rats in the 3.2 mg/kg/day dosage group with brown liver. The gross lesionsofthe liver were considered to be treatment related because the rat nitsessmen Report Appenic V vaso 000333 incidences were dosage-dependent. Significant reductions (p < 0.05 and p < 0.01) in terminal body weights were observed in the 1.6 and 3.2 mg/kg/day dosage groups. Significant reductions (p= 0.05 orp< 0.01) in the absolute weightsofthe seminal vesicles with fluid and the prostate were observed in the 3.2 mg/kg/day dosage group. F, generation female animals: Significant increases (p < 0.05 or p < 0.01) in localized alopecia were observed in the 0.4, 1.6, and 3.2 mg/kg/day dosages groups. Significant reductions in body weight gains and food consumption (p < 0.05 orp < 0.01) were observed in the 1.6 and 3.2 `mg/kg/day dosage during premating and gestation and then in 0.4 mg/kg/day dosage group and above during lactation. Significant reductions (p < 0.01) in gestation length, implantation sites, and litter size was observed at 3.2 mg/kg/day. F, generation offspring: Pup viability was significantly reduced (p < 0.05 or p < 0.01) in the 1.6 and 3.2 mg/kg/day dosage groups. At the doses significant increases (p < 0.05 orp < 0.01) were observed in the numberofdams with stillborn pups, while significant reductions (p < 0.05 or p < 0.01) were observed in the viability index, lactation index, and averages for surviving pups. A dosage-dependent pattemofreduced pup body weight was evident in each dosage group, with statistical significance (p < 0.01) in the 1.6 and 3.2 mg/kg/day dosage groups. F, generation adult animals: Males - Significant reductions (<p 0.05 or p < 0.01) in absolute food consumption at 0.1 and 0.4 mg/kg/day; females - significant (p < 0.05) body weight loss on lactation days 1-4 at 0.4 mg/kg/day; and significant reductions (p < 0.05) in food consumption at 0.4 mg/kg/day on days 1-8 postweaning. F, generation offspring: Pup body weights in the 0.4 mg/kg/day dosage group tended to be reduced, though not significantly, on lactation days 4-21, with significant reductions (p < 0.05 and p < 0.01, respectively) on lactation days 7 and 14, as compared to controls Remarks -- Additional information to adequately assess the data: F, Generation. General toxicity. In male rats, there were no treatment-related clinical signsoftoxicity. Localized alopecia during pre-mating, gestation, and lactation were the only findings reported in some females in the 0.4, 1.6, and 3.2 mg/kg/day dosage groups. Mortality was not seen in cither sex. Reductions in male and female body weight gains and in absolute and relative food consumption occurred in the 1.6 and 3.2 mg/kg/day dosage groups throughout all phases of the study. Following mating, food consumption was significantly reduced in the male 0.4 mg/day dosage group. However, terminal body weight was different than control values only at the 1.6 and 3.2 mg/kg doses. Observations found at necropsy in females were unrelated to treatment. In males a brown discolorationofthe liver was seen in some rats gavaged with 3.2 mg/kg body weight PFOS. Reproductive Toxicity. Male-related effects on mating or any fertility parameters evaluated were not seen in any dose group. While a decrease in prostate and seminal vesicle weight was seen on an absolute basis at 3.2 mg/kg, when expressed as an organ to body weight ratio it was not significantly different from controls. This was interpreted as a generalized effect rather than a rat nial ssssmens Report Appi 060334 specific effect on a reproductive organ. Evaluationof sperm number, motility or morphology was not part of the study protocol. Estrous cycling, mating and fertility were similar among all groups. No statistically significant or biologically important differences in litter averages for corpora lutea, implantations, live and dead embryos were observed in the females examined on DG 10. However, a reduced number of implantation sites and litter sizes was noted, along with an increase in stillborn pups, in the 3.2 `mg/kg dose group that was partofthe main portionof the study. The gestation duration was also significantly reduced at this dose. F, Generation Developmental Toxicity. At the doseof3.2 mg/kg, 71/156 (45.5%) pups were found dead or presumed cannibalized on DL 1; the remaining pups died during DL 2-4. At the 1.6 mg/kg dose, 27/254 (10.6%) were found dead or presumed cannibalized on DL 1; an additional 59/227 (26%) died during DL 2-4. Viability index values demonstrate the steep natureofthe dose-response for pup mortality; values arc 98.7, 98.3, 98.3, 66.1 and 0.0% for the 0, 0.1, 0.4, 1.6 and 3.2 mg/kg dose, respectively. A statistically significant (p < 0.01) reduced pup body weight was seen in the 1.6 and 3.2 `mg/kg/day dosage groups at birth. This effect persisted throughout the lactation period in the 1.6 mg/kg group. There was a tendency for slight reductions in body weight at the lower doses; these differences did not achieve statistical significance. A numberofbiological measures revealed delays in pup development during the lactation period in litters born ofmothers that received 1.6 mg/kg PFOS. These included surface righting reflex, pinna unfolding, eye opening, acoustic stare response, and air righting. The mean age at eye opening was also delayed at the 0.4 mg/kg dose; a transient delay in ageofpinna unfolding was also seen at this dose. Normal development was ultimately achieved for cach of these indices. At weaning the pups in the 1.6 mg/kg dose `group had gained 20% less weight than the controls and for humane considerations, it was determined that no further studies involving these rats would occur and they were cuthanized. `Twenty five cach, male and female F, rats commenced receiving daily gavage dosesof0, 0.1, 0.4 mg/kg PFOS at weaning. This dosing regimen continued through the growth and mating period in both sexes and in females through gestation and 21 days of nursing and lactation. In the post-weaning period, ageofpreputial separation in males and attainmentof vaginal patency in females was similar in control and treated pups in the 0.1 and 0.4. mg/kg dose groups. `Two neurological tests were performed on one rat per sex per litter; passive avoidance at 28 days of age and a water-filled M maze at 70 days of age. No chemically related effects were observed. Reproductive Performance. Body weight gain during the pre-cohabitation period was not significantly different from the controls. At 90 daysofage males and females were mated. After u`nmtaitlinDgLma2l1esatwwehriechkitlliemdeatnhdeynewcerroepskiieldl.edFeamndalneescrwoepsrieeda.llNooweedffteocltisttoernamnadtinnugrsaentdhefierrtyiloiutyng were observed. Body weight during gestation similar to thatof controls except for atransient decrease at DG 1-4 in the 0.4 mg/kg group. No toxicological findings were noted at necropsy. F, Generation rat nial sess Report Appi van 000335 No effect on litter size, numberoflive or stillborn pups were noted. Viability index was 97.1, 98.6,and 96.7 %in 0, 0.1, and 0.4 mg/kg dose groups, respectively. Evidence of treatment related effects were confined to a statistically significant reduced mean body weight in the 0.4 `mg/kg group during unremarkable. the DL 7-14 period. Clinical and necropsy findings in the F, pups were CONCLUSIONS Comment on author's conclusions and whether you agree: Conclusions stated above and this reviewer agrees. REFERENCE Christian, M.S., Hoberman, AM. and York, R.G. 1999b. Argus Research Laboratories, Inc. Protocol Number: 418-008, Sponsor Study Number: 6295.9, June 10, 1999. Final Report Amendment I dated 13 April, 2000. "Combined Oral (Gavage) Fertility, Developmental and Perinatal/Postnatal Reproduction Toxicity Study of PFOS in Rats'. -------- van 000336 { i mgerd poms foro i a . i BE T= ROBUST SUMMARY - RS48 TITLE: Oral (Gavage) Cross-Fostering Study of PFOS in Rats TEST SUBSTANCE Identity: Perflourooctanesulfonate (PFOS) (FC-95) Remarks: The test material was received on 21 October 1998 and stored at room temperature. METHOD Method/Guideline followed: The general guidelines of the FDA were followed. The objective ofthe study was to evaluate the survivalof F1 generation pups following PFOS treatment of FO female during pre-mating, gestation, and lactation. F1 pups were cross fostered during the lactation period to differentiate effects on pups exposed to PFOS in utero and pups exposed to PFOS via maternal milk. Selected tissues were collected from the FO female rats and F1 pups and analyzed to determine the presence and amountof PFOS. Females treated for 42 days with either 0 or 1.6 mg/kg bw/day PFOS were cohabitated with untreated males. All pups ina litter were removed from their dams as soon as parturition was completed and placed with a dam treated with eithe0r or 1.6 mg/kg PFOS. The cross-fostering procedure resulted in four groupsof either 12 or 13 dams & pups, i.c., pups from a control dam fostered on a control dam (CC), pups from a control dam fostered on a PFOS treated dam (CT), pups from a PFOS treated dam fostered on a control dam (TC) or, pups from a PFOS treated dam fostered on a PFOS treated dam (TT). Litters were normalized to 10 pups on DL 4. GLP (Y/N): Yes. The cross-foster study was conducted in compliance with Good Laboratory Practice Regulationsof the US Food and Drug Administration, Japanese Ministryof Health and `Welfare, and the European Economic Community. The analytical analyses for PFOS were also conducted in compliance with FDA Good Laboratory Practices. There were no deviations from the GLP regulations that affected the quality or integrityofeither study. Year study performed: 1998-1999 Species/Strain: Rat. Crl:CD BR VAF (Sprague-Dawley) Number of animals per dose: Twenty five litters from control or treated dams were crossfostered with 12 or 13 control or treated dams; thus four treatment groups were established. In addition, 2 and rats from the 0 and 1.6 mg/kg groups were allowed to keep their litters and `were used as a sourceofbiological specimens for determinationof PFOS levels in dams and pups on DL 14. Maternal serum, liver and mammary gland and pup serum and liver (pooled per litter) were collected. Route of administration: Oral (gavage) ME 000338 Dosing regimen: Female rats were administered appropriate test material daily during a 42 day pre-cohabitation period and continuing through mating, gestation and a 21 day lactation period. Doses were selected based on the resultsof a 2-generation reproductive toxicity study performed using the same route and rat strain in the same laboratory. `Suspensionsofthe test material were prepared daily at concentrations of0 and 0.32mg/mL using 0.5% Tween 80 in reverse osmosis membrane processed deionized water. Doses: 0, 1.6 mg/kg bw/day Statistical methods used: Averages and percentages were calculated. Litter values were uscd where appropriate. Remarks - Detail and discuss any significant protocol parameters: Dayofbirth was designated as lactation day 1. Each liter was evaluated for viability twice cach day. Pup count and physical signs were recorded daily. Pup weights were recorded on DL 1, 4,7, 14 and 21. The lungs and livers were collected from the first 10 culled pups on DL 4 and preserved. On DL 21 six litters from eachofthe four cross-foster subsets had pooled litter samplesof liver and serum collected for possible analysis for PFOS. RESULTS `Toxic responses - maternal: All FO females survived to scheduled sacrifice. There were no clinical or necropsy observations attributed to PFOS administration. Absolute body weights were slightly reduced in the 1.6 mg/kg groups at the endof cohabitation and continued through gestation and lactation. Feed consumption was also reduced in the group throughout the study. Litter size at birth was slightly reduced in the 1.6 mg/kg group, 16.2 and 14.8 in the 0 and 1.6 mg/kg groups, respectively. Nuomfimbplaentatrion sites in the 1.6 mg/kg group was also reduced, 16.0 vs. 17.7 in control Toxic response -- pups: Pup mortality is summarised in the table below. It was increased in pups from treated dams that foster nursed control dams. Mortality was greatest in pups from treated dams that foster nursed treated dams. There were no differences in mortality in pups from control dams that foster-nursed treated dams when compared with pups from control dams that foster nursed control dams. PFOS exposure via maternal milk appeared to reduce pup body weight gain regardlessof in utero exposure to the chemical. For example, mean pup weight per litter was 29.0 (CC), 26.2 (CT), 26.7 (TC) and 24.6 (T'T) grams on DL 14. The greatest reduction in weight gain was in those pups exposed in utero and during lactation. Evaluationoflivers from LDI pups from dams in the 1.6 mg/kg group revealed increased (2X) cneulmlbmeermsborfanpeersowxeirsoemneostwohbseenrveexd.amTiynpeed bIIypenleeuctmroocnymtiecsrwosecroepyin.crDeiafsfeedreinncensuminbemritaoschwoenrderitahle numberoflamellar bodies in samplesof lung. ret iltscssmens por Append V vais 000339 Cross-foster PFOS Study Postnatal Pup Effects During 21 Day Lactation Period PFOS Exposure' Number Total Percent Litters Pup Gestation Lactation Dead Pups Mortality Affected Weight 0 0 3 9 16 302 200 0 16 2 181 20 201) 262 16 0 16 166 96 10011) 267 16 16 3 7 192 812) 246 # refers to daily female doseof 0 or 1.6 mg/kg PFOS. *mean weight in Grams on LD 14. Additional information to adequately assess the data: Serum samples collected from dams and litters on scheduled day of necropsy (LD 21) have been analyzed for PFOS content and the resultsarepresented below. Other samples have not been analyzed. Pooled sera from liters born of control dams that were cross-fostered on control dams had values below the lower limit of detectionasdid their foster mothers. In contrast, pooled sera from liters bornoftreated dams who also foster nursed treated dams had values of 89.71 uG/mL, similar to their foster mothers and other treated mothers. Pooled sera from liters bornoftreated dams but who foster nursed control dams had values that were 60% (53.88 ug/mL)ofthe TT litters. Interestingly, their control foster mothers developed low sera values probably as a result ofgrooming their litters and coprophagy. Pooled sera from litters bomof control dams that foster-nursed treated dams had PFOS valuesof 22.35 ug/ml. indicating significant transfer of PFOS through milk. Considering pup viability data it is suggested that matemal sera levels in the rangeof 82-89 ug/L are associated with pup mortality. Dra iilAsses Report ppenic vig 000340 PFOS Values in Serum Collected From Dams and Pups at Time of Necropsy Pup Exposure Regimen Gestation Lactation Nursing Dams Mean Litters Pooled Mean Control Control 005" (12) 0.05" (6) Control Treated 8296 (13) 2235 (6) Treated Control 202 (13) 53.88 (6) Treated Treated 8.97 (12) 8971 (6) ***0N.0u5mbueGr/miLn piasrLeonwtehresLeismiitsonfuQmubanetritoaftisoanm.ples CONCLUSIONS In utero exposure to 1.6 mg/kg PFOS can cause postnatal pup mortality. Continued PFOS exposure in the postnatal period appears to have an additive effect on the incidenceofpostnatal pup mortality. At 1.6 mg/kg effects on maternal weight, implantations and liter size were similar 10 those observed in a prior 2 generation study. Significant quantities ofPFOS appear to be scereted in milk. The quantities secreted in milk can plausibly account for the additive mortality in pups exposed in utero and through lactation compared to mortality levels in pups solely exposed in utero. Sera levels in pups exposed to PFOS during gestation and lactation are equivalent to maternal values at time of weaning Commenotn author's conclusions and whether you agree: Agree REFERENCE Christian M, Hoberman AM & York RG. Argus Research Laboratories, July 23, 1999. Oral (Gavage) Cross-Fostering Studyof PFOS in Rats. Protocol 418-014 Sponsor Study T-6295.13 CD 00001108pdf Hansen KJ, Perkins JR. 3M Environmental Laboratory, June 28, 1999. Analytical Laboratory Report Report on Determinationofthe PresenceofPFOS Number U2779. Sponsor Study T-6295.13 in the Serumof Sprague-Dawley Rats. Lab Nold JM. Pathology Associates Intemational, April 5, 1999. ------ Vass 000341 ROBUST SUMMARY - RS49 Title: Ninety day subacute rat toxicity study TEST SUBSTANCE Identity: N-EtFOSE alcohol Remarks: Lot FM-03422 41d-2700-3422-0 Lot 784/ Net-35 DR-1 METHOD Method/guideline: Not listed Study duration: 90 days GLP: No, prior to start of GLP Year study performed: 1978 Species/Strain: Rat; Charles River CD Route of administration: Oral, diet Doses tested and frequency: 100, 300, 1,000, 3,000 and 10,000 ppm in initial (11/4/1977) trial, an addition 30 ppm group initiated 11/25/1977 in accordance with an approved protocol modification. Treated feed available ad lib. Sex: Male and female Control group and treatment: Purina Laboratory Chow (ground basal dict) Post exposure observation period: none Statistical methods: Analysis of variance (1-way classification), Bartlett=s test for homogeneityofvariances, and the Aappropriate t-test (for equal or unequal variances) as described by Steel and Torrie, using Dunnett=s multiple comparison tables to judge significance ofdifferences Remarks: Test Subjects: Age at study initiation: not specified `Weight at study initiation: 240-306 g (male); 180-226 g (female) No. of animals per sex per dose: 5 Study Design: Vehicle: Purina lab chow Satellite groups and reasons they were added: none Clinical observations performed and frequency: Animals observed twice daily for duration of trial. Body weight, food consumption, gross behavior, eyes, nose, mouth. eOyregsa,nhseaertxa(wmiitnhecdoraotnnaercyrovpesssye:ls)A.drDeunoadlse,nuamor,tai,lbeoumn,e,jebjruainnum(,wictohlosne,gkmiednnteoyfs,cleirvveirc,allucnogr,d) thymus, mammary gland, nerve (with muscle) spleen pancreas, prostate/uterus, bone marrow J -------- Yoosez (sternum) salivary gland, spinal cord (lumbar) pituitary, stomach, testes/ovaries,thyroid, parathyroid, urinary bladder, mesenteric lymph node, and any other tissues with abnormalities. RESULTS NOAEL (NOEL) 30 ppm NOAEL/LOEL (because of lackofstatistical significance and additionof 30 ppmgrouppost hoc) LOAEL (LOEL) 100 ppm LOAEL Remarks: Body weight: e ee w. w me] Ts wor| wen | Food/water consumption: Dose (ppm) Toaww | Average Food Consumption (g/ratday) mew] ET Femile we "Statisticallysignificant relative contolap001, Clinical signs (description, severity, timeof onset and duration): ii a boon l[iommeornT [+T TwT Tw |owT J wow[| T oww w[]om [vespome|]TT] +] fempen ]T--T55]| =--T ; im Netw |TT5|T 5] Haematology: For rats at the 30 and 100 ppm dosage at 1 and 3 months of study, and for rats treated at 300 ppm at 1 month, all hematological levels were within the expected range. 3w`meornethsteatriystthircoalclyytesicgonuinftisc,anhtleymolgolwoerbirnelaantidvehetmoactoonctrroilts.vaAllulesotfhoerrmhaelmeataonldofgeimcavlaelruaetss water3e00noPtP significantly different from controls at the conclusionof thestudy. Biochemistry: Statistically significant responses (see table): Glucose elevaled in female rats at 300 ppm; BUN elevated in males at 300 ppm; Alkaline phosphatase elevated in males and females at 300 ppm; PGOT decreased in males at 100 ppm, but not at 300 ppm. PGPT elevated in males at 300 ppm. No compound related changes noted in urinalysis Slewlawlaw]o] I ws000344 [Frermem|CelaTmweeTlouelel=elne|] Summaryof Biochemistry Results from 90 Day Study ] 1 IB 6 2 Creatine | Pretest | prosphokinsse 1 25 6 20 8 5 6 5 9 10 13 [catciummeat,| pretest 02 | 98 | 75 | 77 | 107 | 97 | 07 | 9s | Si, PG=PplaTsma glutamic pyruvic mansaminase PGOT = plasma glutamic oxalacete transaminase hmoechng `Mortalityand time to death: (see table below. Time to death not reported). rarer -- I tiem || ve000345 IEE Loo |ow [ow] [oo | wo [ow] Gross pathology incidence andseverity: Liver Lesions: All rat treated at 300 ppm exhibited compound-related gross liver lesions, occurring singly or in combination. Changes included liver enlargement, accentuated Iobulations, diffuse brown discoloration and gray/yellow/white areasofdiscoloration. Males appears to be more severely affected than females. Similar but less severe liver lesion observed in animals from the 100, 1,000, and 3,000ppm groups. Stomach: Compound related gross lesions including hyperemia/congenstion, red/brown foci/hemorrhage in the some animals receiving 1,000, 3,000, or 10,000 ppm. Organ weight changes: Liver: Statistically significant increase in absolute and relative liver weights in 100 and 300 ppm groups, with males more severely affected than females. Other organs: statistically significant variations observed at 100 and 300 ppm, without `morphological changes (see table). ref niasss ReposAppend vas 000346 [ooame Towwno[wsoJ[woasenJ[ceommss[[ro=o]] [[oromaarrsams| 0 0 | [roismeerJeoeeJ[oooor]] Histopathology: Liver: Microscopic alteration observed in livers from all treated groups consisting ofvery slight to marked centrilobular to pan-lobular hepatocytic hypertrophy in 30, 100, 300, and 1,000 ppm groups. Hepatocytic hyperplasia observed in the 3,000 and 10,000 ppm groups. Very slight to moderate increase in lipid-containing cytoplasmic vacuoles at 100 and 300 ppm. Focal to multifocal coagulative centrilobular to midzonal hepatocellular necrosis of very slight to marked severity observed in 300, 1,000, 3,000 and 10,000 groups. Minimal amount of associated hienpfaltaomcmyatteosryanidnfKilutprfafteerobcseelrlsveodb.sIenrcvreedasperdimianrtirlaycyatto3p0la0smpipcm.accKuulpuflfaetirocnoelflsbsrtoaiwnnedpipgosmietnitvse in for iron; hepatocytes did not. Kidneys: Most animals in the 300 ppm group exhibited very slight to marked tubular nephrosis with associated proteinaceous cast formation, and intracellular accumulationof brown pigment (staining positive for iron) and reddish-brown hyaline droplets in tubular epithelial cells. Mineralizationof luminal tubular debris observed in some rats. Other tissues: Lesions in other tissues were not considered compound-related. CONCLUSIONS 30 ppm Slightly depressed weight gain compared to controls. Significant increase in y-GTP in `males and females, but no dose-dependence. 100 ppm Reduction in body weight for both sexes; depressed food consumption in females, one female rat demonstrated behavioral change. Statistically significant liver weight increase. 300 and ppm food 2 premature consumption deaths in females following blood collection. were significantly lower. Hematologic values Group mean (erythrocyte body`weights count, `hemoglobin and hematocrit were slightly but statistically significantly lower than controls. Changes observed in biochemical values (e.g., alkaline phosphatase, PGPT, PGOT, y-GTP and BUN). Gross liver lesions observed. Statistically significant liver weight increase; changes in kidneys observed. beter Se Remarks: Although old, study appears to have been well conducted and results well reported. It clearly would have benefited from having a range-finding study. Some concem about post hoc. addition of 30 ppm group, and the lackofan additional control group entering at the same time, which makes dose spacing it to difficutlot rely wholeheartedly on the next exposure level was 3-fold the effects noted and not 10-fold, at it 30 ppm. Given that the is not inappropriate to consider 30 ppm a NOEL, and 100 ppm a LOAEL. REFERENCE International Research and Development Corporation. 1978. Ninety day subacute rat toxicity study on FM-3422. IRDC Study No. 137-086. Final Report, November 10, 1978. Draftsessment Report Appenic Vass 000348 ROBUST SUMMARY- RS50 `Title: Ninety Day Subacute Rhesus Monkey Toxicity Study. TEST SUBSTANCE Identity: N-E(FOSE alcohol Remarks: FM-3422 41-2700-3422-) Lot 784/Net-35 DR-1 METHOD Method/guideline: Nonespecified Test type: 90 day gavage GLP: None specified Year: Study performed in 1978; final report 1979 Species: Monkey Strain: Rhesus Route of administration: oral gavage Doses/concentration levels: 1,3, 10, 30 mg/kg/day Sex: Male and female Exposure period: 90 days Frequency of treatment: daily Control group and treatment: propylene glycol Post exposure observation period: none Duration of test: 90 days oStfavtairsitiacnaclesm,eatnhdodtsh:e AAanpaplryospirsioatfevarti-taenscte(f(o1r-ewqauyalcloarssuinfeiqcautailonv)a,rBiaarntcleest)t=ass dteesstcfroirbehdomboygSetneeeilty and Torrie, using Dunnett=s multiple comparison tables tojudge significanceofdifferences. Remarks: On days thereafter, days 2 ml 1 and 2of was used. study, test material Controls mirrored was dissolved in treatment groups. 5 ml propylene glycol; on all Test Subjects: Age at study initiation: Not specified Weight at study initiation: males: 3.04.35 kg; females 3.05-4.20 kg No.ofanimals per sex per dose: 2 Study Design: Vehicle: propylene glycol Satellite groups and reasons they were added: none bCleihnaivciaolroabnsderpvhaatrimoancsotpoexrifcosrimgensd. aInnddifvrieduqaulenbcoyd:y wtweiicgehtdsairleycoforrdegdenweereakllpyh;ysgiecnaelraalpppheyasriacnacle, ref nia Assn Report Append vase 000349 oexnacmeipnraitoirotnostmhoenbtehgliynndiunrgionfg stthuedey.xpeHreimmaetnotl,ogaincdala,t b1iaoncdhe3mimcoanlthasnodfusrtiunadl.ysis were conducted Organs examined at necropsy: brain, eyes, thyroid/parathyroid. heart, liver, adrenals, spleen, pituitary, kidneys, testes/ovarics, RESULTS NOAEL (NOEL): 10 mg/kg/day LOAEL (LOEL): 30 mg/kg/day Remarks: ofBosdtyudwyeiagllhtt:heDmuorniknegytshweefriresat tmoonrthn,eaarllthmeoonrkiegiynsalinbcolduydiwnegicgohnttreoxlcsepltostfowreitghhet.groAutps1r2ewceeievkisng `1w0eiagnhdt l3o0ssmgw/aksg/odbasye.rvAeldthfoorugahnyongeromuopnaktetyheschoonwceludsaiowneoifgthhteloesxsp,enroimsetnatti.stically significant Food/water consumption: Food consumption was cstimated. tChleinsitcuadly,siagllnsth(edemsocnrkiepytiso,n,inscelvuedriintgy,cotnitmreoolsf, osnhsoewteadnsdlidguhrtattoiomna)r:keOdndeacnrdeaasfeteirntahcetsiveictoy,nd day ataxia, glycol and was raneodruecxeida.frTohme5attoax2iamld/iskagpopneasrteuddyfrdoamy all 3. tSheevmeroanlkweeyeskasftienrtothteheamsotuudnyt,osftpoorlopylene ocbhsaenrgveesdwienrmeoosbtseorfvtehde imnotnhkeemyosnkferyosm,cwaicthhgbroluapc.k sTtowolo,omfutchuesmaonndkeblyosordeycemiuvciungs3i0n tmhge/kstgo/odlay had these symptoms persist for mostofthe treatment period. Haematology: mg/kg/day exhibited a No unusual changes observed slight decrease in hematocrit, for blood. One monkey receiving 10 hemoglobin and erythrocyte counts at 1 `month ofstudy that was ot observed at 3 months. Biochemistry: Glucose: lower range of expected values. Most ofthe monkeys exhibited blood glucose values in the 2Chmoloenskteeryosl:re1cemiovninkge3y0rpecpemivsinhgow1e0dmgl/okwgc/hdoalyes(tesrhoolwveadluaelso(w56chaonldes6te7romlg/l1ev0e0lm(l8,4 amlgs/o1w0i0tmhl)l;ow potassium (3.5 meq/L)). Ophthalmologic findings: None reported. tMhoertsatuldiyt.y aDneadthtiwmaestoprdeecaetdhe:d Obynea mmoarnkkeedylroescseoifvbiongd3y0wmegi/gkhgt/(d1a.y25dikegd)dwuirtihngattahxeialaasntdwaeek of marked decrease in activity. All other monkeys survived until sacrifice Gross pathology incidence and observed at the endofthe study. severity: No gross lesions considered compound-related were aOnrdgabrnaiwneiinghatnicmhaalnsgetrse:ateSdtaattis1t0icaalnldy 3si0gnmigf/ikcga/ndtavya.riaNtoionmsoripnhsoelxoggircoaulp cmheaanngewseiwgehrtesoofblsievrevred in these organs relative to control. Dra iilAsses Report Append vast 000350 Te = fr | 0 D (mg/kg/day) oJoe Joe oo] [on[00 I5o oomwer relative JJoomnmee 0oo]] Histopathology: 1,3, or 10 mg/kg/day: No changeswereobserved in tissues. 30 mg/kg/day: One male and two females exhibited slight to severe lipid depletion in adrenal gcellalndssi.ze Tanwdolfoessmoaflzesymexohgibeintegdramnoudleesr.atOenaetrpoapnhcyorefatshaelspoahncardeasteivecreaxloecorsiinneocpehlillsi,cwiintthradneuccrleeaasre inclusions in the exocrine cells. No changes in tissues other than the adrenal glands and pancreas were considered compound-related. CONCLUSIONS Clear NOEL and LOEL can be derived from this.study. Remarks: Old, but generally well-conducted study. Some concerns about effectof vehicle, due etxoaGcIersbyamtipotnoomfssiynmapltl oamnsim.als, although there does appear to be a compound-related REFERENCE International Research and Development Corporation. 1979. Ninety Day Subacute Rhesus Monkey Toxicity Study, on FM-3422. IRDC Study No. 137-088. Final Report, January 16, 1979. OR -- ROBUST SUMMARY - RSS1 TPietrlfel:uo1r0oo4c-tWaeneeksuDlifeotnaarmyidCoarEctihnaongoelniicniRtaytsS.tuSdyUwMitMhANRarYroRwERPanOgRe-T(9W8.E1E%)KN-5E3thylTEST SUBSTANCE Identity: N-Ethyl Perflurooctanesulfonamido Ethanol (N-EtFOSE alcohol) cRoemmpaoruknsd:sTest substance is Anarrow range, consistingof98.1% N-EFOSE plus other related METHOD Method/guideline: None Test type: 104 week oral toxicity study (Week 53 Interim Report) GLP: Yes `Year: Not specified (Study start date: January 26, 1998) Species/Strain: Rat; Crl:CD'(SD)IGS BR Route of administration: Oral (in chow) Doses/concentration and 1 ppm N-EFOSE levels: 0, 3, 30,100, 300 alcohol added at a ater ppm date) N-E(FOSE alcohol (Additional doses of0 Sex: Male & Female Exposure period: 104 weeks (53 week interim) Frequency of treatment: ad libitum Control group and treatment: Concurrent vehicle: Post exposure observation period: At least 52 weeks following 52 weeksofexposure Duration of test: 104 weeks (53 week interim) Statistical methods: Not specified in Week 53 Summary Report Remarks: Test Subjects: Age at study initiation: 6-8 weeks Weight at study initiation: 100-300 g No. per of animals per sexper dose: sex in 30 ppm dose group, 70 70 per sex per sex in in control group, 60 per 100 ppm dose group, 70 sex per in 3 sex ppm dose group, in 300 ppm dose 60 group, 40 per sex in 100 in 1 ppm dose group, 70 ppm recovery group, per sex in additional c4o0ntpreorlssefxoritnh3e010ppppmmdroesceovgerroyupg.roup, 70 per sex Study Design: Vehicle: Chow Satellite groups andreasons they were added: Not specified in Weck 53 Summary Report Cdlaiinliyc(aalmobasnedrvpamt).ionEspaecrhfaonrimmaeldwaansd frreemqouveendcyf:roOmbsceargveeadndforexmaomribnideidtoyn/mcoerpirbiuonrdtiotytrtewaitcmeent ET -------------- vas 000352 oanncdeoenvceerywe4ckwleyektshertehaefrteearf.ter.FooBdodcyonwseuimgphttisownedraetadewteerremicnoelldewcteeedklfoyrfWoereWkesek1sth1rtohurgohug1h6 a1n7d uarnidneonccheemeivsetrryy,4awnedeukrsintahleyrseiasflwere.reBcloololdecatnedd furrionme$saamnpilmealssfpoerrhesmexationltohgey,cocnltirnoilcaalncdhehmiigshtry, gdroosuepgrdouurpisngdWureienkgsW1e4e,k278, aanndd f53r.omB1l0ooadniamnadlsurpienresseaxmpinletshefo1rphpemmadtoosleogayn,dcslienciocnald control scehxemiinsttrhye,cuonrtirnoel,ch3e,mi3s0,trayn,dur1i0n0alpyspims, daonsde sgerrouumpssdaumrpilnigngWeweerkes c1o4l,le2c7t,edanfdro53m. 10Blaonoidmaslasmppelres `foWrecsker4u;mfranoaml5ysaensiwmearles pcoelrlseecxteidnftrhoemcoSntarnoilm,a3l,s3p0e,r1s0e0x,iannadll3b0u0tptphemrdeocsoevegrryougrposudpusridnugring a`nWdecfkr8o;mf5raonmi$maalnsimpaelrsspeexrisnetxheinboaltlhbcuotnttrhoelhgirgohudpos,sethaend1,raencdovtehrey1g0r0oupppsmdudroisneggWreouepks 1d4u;ring Week 53. fToelrlmoiwniantgitoinmescihnetderuvlael:s:5 Waneiemkal4s:pAelrlsgerxouwpesrebnuectrhoeprseiceodveforrytghreoufposl;loWwienegkg8r:ouCposntarotlheand 300 ppm dose groups; Week 14: Both control groups, 1, 3, 30, and 100 ppm dose groups. During Week the additional 53, ive control, atnhiem1a,lasnpderthseex10f0ropmpmthedoisnietigarlocuopnstrwoelrgeroneucproapnsdie1d0.animals per sex from eNfOfeTcEts:sDeuernifnogr Wboedcykw8e,igthhte,30fo0opdpcmondsousmeptgiroonu,psanwdercelinriecmalovpeadthforloomgytahendsttuhdeyrbeemcaaiunsienogfhtiogxhic dose non-recovery concurrent control animals were discarded without group were subsequently added. necropsy. The 1 ppm dose group and its Organs examined at necropsy: lOurngga,novwaeriyg,hts:plAetenW,eteeskte4s,,otnhlyyrotihde/plairvaetrhwyaroside,vaalnuadtoevda.rieWse.ekWe8:eAkd1r4e:naFlo,rbcroanitnr,olk,id3n,e3y0s,, alinvder1,00 ppaprmathdyorsoeidg,roaunpds,ovaadrrieensalwse,rberaeixna,mkiindende.ys,Folrivetrh,elaudndgi,tioovnaarly,cosnptlreoeln,antedst1esp,ptmhydrooisdewgirtohups, only the liver was evaluated. thyroid/parathyroid, and Week 53: ovaries. Adrenal, brain, kidneys, liver, lung, ovary, spleen, testes, cMoircdr,oskcidonpeiyc,elxiavemri,ntathiyomnu:s,AtlyWmepehkn4o,doensl(ymtehseenltievreircw,amsanedvailbuualtaerd., meWdeieaskti8n:aEl)y,e,spblreaeinn,, spiptiuniatlary, aWdereenkal1,4: stFoomraccohn,trdoul,od3e, n3u0m, ,ajnedju1n0u0mp,ppmandcorseeasg,roeuppisd,ideyymei,dbersa,int,eskteisd,neoyv,arliievse,r,vmaegisnean,teurteircus, 1lypmppmh dnoosdeesg,rsopulpese,n,liavderrewnaals,epxaanmcirneeads., teesteesk, o5v3a:riEeyse,,vbargaiinna,,suptienrauls.corFdo,rkaidddnietyi,onlailvecro,ntlrunogl,and thheayrrto,idfewmietrh bpaornaethwyirtohidm,artrraocwh,eas,teesmopuhmagbuosn,eswailtivhamryargrloanwd,s,skhealretdaelrimaunscgllean,ds,ctiahtyimcunse,rvley,mph sntoodmeasc(hm,esceonltoenr,irce,cmtaudmi,bduluaord,enmeudmi,asjteijnuanlu,ml,umiblaeru/mi,lpaacn)c,rsepalse,enb,lapdidteuri,tasrkyi,na,dmreanmalm,acreycugml,and, prostate, seminal vesicles, epididymides, testes, ovaries, cervix, vagina, uterus, tail oCorlglaencwteedigohrtgsanwserweerneotalrseocoerxdaemdiannedd lmiavcerrossacmoppliecsalwlye.reUnnostcchoeldleuclteedd.deaths were necropsied, but Additional Endpoints: Dra nilAsset Report Append vaso 000353 Proliferation Cell Nuclear Antigen (PCNA) evaluation Mitochondrial control, 3,30, analyses: 100, and Liver samples collected 300 ppm dose groups. from animals sacrificed during Week 4 from the Palmitoyl-CoA oxidase analyses RESULTS NOAEL (NOEL): Week 53 Interim Report: 3 ppm LOAEL (LOEL): Week 53 Interim Report: 30 ppm (decreased cholesterol levels) Rpepmmahrakds:sigBniofdiycawnetliyghlto:weArftbeordtyhewefiirgsthtwseceokmofptarreeadtmtoencto,ntraonlism.alAsngiimvaelnsdionsethseof301p00pmord3o0s0e gstraotuisptihcaaldlylsoiwgenrifbiocdanytwuenitiglhtasppcroomxpiamraetedltyoWceonetkrol8.s, Bbuotdythweediifgfhesroefnaceniwmaaslnsotingetnheera1lolry3 ppm dToowseergfroorupasniwmearles niontthseig3ni0f0icpapntmlyddoisfefegrreonutpfsrwohmecnonctroomlps.arBedodtyo cwoenitgrhotlsgabiengiwnansinsgiginniftihceanfitrlsyt wweeiegkhotfgatirne;atmfoerntt.he A3n0ipmaplmsdionstehegr1o0u0p,pcphmandgoessewgerroeupsspofrraedqiuceanltllyyshiagndifsiicgannitf.icOanvtelryalllowcehranbgoedy in body weight (Week 1 ppm dose groups. Body to Week 53) was significantly weight gainofanimals in the lower 1 or 3 than ppm controls for dose groups the was 100 not and the 30 significantly different from controls. Ffoooodd/cwoantseurmpctoinosnumcpotmipoanr:edAntiomcaolnstrionlsthseta1r0ti0nganidn t3h0e0fprsptmwdeoeskeofgrtoreuaptsmehnatd,sigSntiafritcianngtilny Wloeweekr 3i,ntmearvlaelss iwnhtehne 3co0mpppamreddostoecgornoturoplhaandimaanlsu.mbTehriosfesfifgenctifwiacasntnloyt loobwseerrvfeododfocrotnhseufmepmtailoens in the same dose group, nor for the animals in the 1 and 3 ppm dose groups. Test Material Consumption: The following consumed by animals on a mg/kg/day basis: table summarizes the amountof test material raf ni sss Report Append vast 000354 Cm Achieved Dose Levels - Range (mg/kg/day) ere owaw Clinical signs (description, severity, timeof onset and duration): There were no apparent test material-related observation noted through Week 53. Hematology: At a dose levelof 300 ppm for approximately 8 weeks, administrationofN- EtFOSE alcohol was associated with hematological effects, including lower red blood cell count, `hemoglobin, and hematocrit. Mostofthe effects were moderate to marked in magnitude. `Dcioeutnta,ryheamdmoignliosbtirna,tiaonnod fheNm-atEotcFriOtSEforalfceomhaollewsaisn tahseso1c0ia0tpedp`mwidtohsmeilgdrloyupdse.crNeoaseefdfercetds blood were cell seen for the 1 and 3 ppm dose groups. Clinical Chemistry: At a dose level of 300 ppm for approximately 8 weeks, administration of N- gEltoFbuOlSinE,waansd acshsoolceistaetreodl,wiatnhdmhainghyerefufreectasnointrcolgienni,caallbcuhmeimni,sttroytarlebsiulltisr,ubiinncl(umdailnegs loonwlye)rg,lucose, aspartate aminotransferase (males only), and alanine aminotransferase. Mostof the effects were `moderate to marked in magnitude. Mildly lower glucose and (predominantly at Weeks `mildly 14 and higher urea 27). Males gniivternoge1n00wapspmobwseerreveodbsfoerarvneidmatolshagvievemnod1e0r0atpeplmy higher albumin and moderately lower globulin (predominantly at Weeks 27 and 53). Males given 30 or 100ppm and females given 100ppm had moderately to `markedly lower cholesterol. No effects were seen for the 1 and 3 ppm dose groups. Ophthalmologicfindings: Not performed `Mortality andtimeto death: Two males and 2 females given 1 ppm, 2 males given 3 ppm, one `male and one female given 30 ppm, 6 males and one female given 100 ppm, 4 males given 300 ppm, and a total of8 control animals died on test or were sacrificed `moribund. Oneof the males given undet 3 ppm was ermined for sacrificed one male due to a fractureofthe given 100ppm and one hard palate. male given The causeof death was 300 ppm. Histopathology w as not performed on animals from the I ppm dose groups; the macroscopic findings were typical of those observed in rats in long term studies. All ofthe other treated animals that died or were 000355 sacrificed at to treatment unscheduled with the test intervals material, ohradbo`thhe.paOtfoctuhlleuslearanhiympaelrst,rtohpehy3 or `hepatocellular ppm dose group necrosis due male was msaaclreifainceddobneeca3u0seppomfadolasregegrsouubpcufteamnaeloeusweurnedisfafcerriefnitcieadtemdorsiarbcuonmda,wiotnhep3it0u0itparpymaddeonsoemgarso,up hepatocellular ppm, and one necrosis 100 ppm dwoassetghreocuapusmeaolfeddeiaetdhwifotrh2nemcarloessisogifvetnhe1m0u0spcuplmataunrdeo3ftmahleesanguisv,en 300 The following table summarizes the survival data for the 53 week interimreport: en [ree] omll aene Taw m] oomm] weoo wwee] ome |oe Gross pathology incidence and severity: Week 4: No gross findings. lWieveerkwa8:sEonblsaerrgveeddliinveornsewefreemafloeu(n3d0i0npapllmoftdohsee `gmraolueps).andTh2eorfetwheerefenmoaloetshearnadb`nmoorttmlailng of the `macroscopic findings. Week 14: No gross findings. Week 53: No grossfindings. Organ weight. changes: Week 4: Absolute dose groups. and relative liver `weights were higher for animals in the 100 and 300ppm. dWoeseekgr8:ouApbs(oolnultyetraenadtmreelnattigvreoulipveerxawmeiingehdt)s.weTrheerseigwniefriecannotloythhiegrhteerstfomrataenriimaal-lrseliant3ed00chpapnmges for absolute or relative organ weights. Week 14: ppm dose gArbosuopl,utbeutannodtrfeolratainveimlailvesrfwreoimghtthse were 1, 3, significantly higher for or 30 ppm dose group. animals from the 100 There were no other test material-related changes for absolute or relative organ weights. J Boose Week 53: ppm dose gArbosuopl,utbeutannodtfroerlaatniivemlailvserfwreoimghtthse w1eprpesmigdnoisfiecgarnotulpys.higThheerrefowrearneimnaolsotfhreormtetshte 100 material-related changes for absolute or relative organ weights. Histopathology: Wtheeelkiv8e:rsoHefpaantoicmealllsulfarrohmytpheert3r0o0phpyp, mhedpoasteocgerloluulpa.r necrosis, and hemorrhage were Other findings unremarkable. observed for Week given 14: 100 Hpeppma.tocOetlhleurlafrinhdyipnegrsturnorpehmyawrakasboleb.served for males given 30 or 100 ppm and females pWpemekdo53s:e Hgreopuapt.oceHlelpualtaorcehlylpuelratrrnoepchryosainsdwvaascuooblsaetriovnedweforreoonbesemravleedafnodr a2nfiemmaallsefsrformotmhteh1e01000 pOpnmed1o0s0epgpromupdsosaendgroonuepmfaelmealaenhda2d faehmeaplaetsocferlolmultahrea1d0e0nopmpam, dwohsiechgraoruepocecxahsiibointaeldlbyiloebsstearsivse,d as an incidental finding in 1 year old rats. Other findings unremarkable. Additional Endpoints: `PrSoulmimfearraytiRoenpCoerltl (NauncalleysairsApnetrifgoernm(edPCbNyAS)poenvsaolura)tion: Results not provided in Week 53 Mitochodrial by Sponsor) analyses: Results not provided in Week 53 Summary Report (analysis performed PEa(lFmOiStEoyall-cCoohAoloxwiadsasaessaoncailaytseeds:wiAtth tmhieldWley,ekbu4t astnadtiWsteiceaklly8ssiagcnriiffiiccaenst, hadimgihneirshterpaattiiocnpoaflNmi-toylCoA oxidase activity in the animals given 300 ppm. CONCLUSIONS CchhorloensitcerdoiletinarryatesxaptoasudroesetolNev-eEltoFfO3S0Epaplmcoahonld wabaosvea.ssoHceipaatteodcweiltluhldaerchryepaesretdrloepvheylsaonfd other threepaattmoecnetl-lruellaarteefdfeecftfsecwtesrweeroebsoebrsveerdveidn aatniamnalesxpforsoumrethleev3e0l oanf3d 1p0p0mp.pm dose groups. No REFERENCE CRoavnagnec(e98L.ab1o%r)atNo-rEitehsylI-ncP.erfNlouoDratoeo.cta1n0c4s-uWlefeoknaDmiiedtoarEythCaanrocliniongReantisc.itSy UStMuMdyAwRitYh RNaErPrOowRT WEEK 53. Prepared for 3M. COVANCE STUDY NUMBERS: 6329-212 and -228. [ -------- Vaiss 000357 -- ROBUST SUMMARY - RS52 Title: Oral (Gavage) Pharmacokinetic Recovery Study of PFOS in Rats (1999) TEST SUBSTANCE Identity: Perfluorooctylsulfonate, potassium salt (FC-95), CAS 2795-39-3 Remarks: Purity 98.9%, Lot #217 METHOD Method/guideline followed: GLP, FDA, EEC Test type: in vivo Species/strainicell type or line: rat/Sprague-Dawley/pregnant Crl:CD(R)BR VAF/Plus(R) Sex: Fo: female, Fl: both Age and body weight range of animals used: 65 days, 192-231 g Number of animals/sex/dose: Fo: 8, F1: 5 male and female pups/ltter Routeof administration: oral Vehicle: 0.5% Tween(R) 80 in R.0. deionized water, dosage volume ml/kg Dproisoerst:o c0oh(vaebhiitcaltei)o,n0u.n1tialncdon1.f6irmmge/dkge/vdiadyenicnevooflmuamteinog.fSOmnilkyg,thoenFcoe fdeaimlaylebsegwienrneindgos4ed3.days Excretion routes, body fluids, Fo urine, feces, serum, liver. F1 and tissues monitored liver and serum. and/or sampled during study: Statistical methods used: averages and percentages Minetterhvoalds:roenmeardkasy:prUirorinteo ainnidtifaetciaolnosfamcpolheabsiwteatrieoncotloletchteedfoflrloowmiFnOg mfoemmailneg,ratdsafyosr6thteo f7o,l1l4owtiong (15D,LSa)nd2120toto222.1oBflporoedsusammepdlegseswteatrieonco(lDleGcste6d tforo7,m 1e4acthoof15t,haendma2t0ertnoa2l1)r,atasnodndtahyesdofalyactation csouhravbiivtiantgiroantswaasssiinginteidatteod t(phreiosrtutdoycwoeharbeitsaatciroifni)c,eDd Gosn D7,L1522.andA2l1i,vearnsdeDctLison1w4aasncdol22l.octAeldlfrom cach dam. aDnadyf1iovfelfaecmtaalteiopnupwsaspedrefliitneerd, awshetrheedpaosysoibflbei.rthO.nODnLD2L1,4a,lllirtetemrasiwneirnegcpuulplsedwteorefisvaecrmiafliecedp.ups rTehfe nliiavlerAsfsrcsommencsRaecphorptuAppwpeansdcollected and pooled per litter. Blood samples were collVecatsesd and 000358 pooled per liter. UOrnindea,ysfec1al1,0 s4eorfutmhean4d3-lidvaeyr spraemmpalteisnwgepreerisohdi,pFpeodfteomatlhee Sraptosnrseecreifvoerdan2a5ly%sigsreater dose due to an incorrect calculated amountoftest substance in vehicle, RESULTS Detailed results: PK results not final. Metabolites measured: none CONCLUSIONS REFERENCE OLraabolra(tGoarviaegse,)InPch.arPrmoatcoockoilnc4t1i8c-0R1e5c,o3veMryReSfteurdeynocfe PNoF.OST-6i2n9R5a.t1s4,,FiAndavlaRnecpeordtB,iAoarngaulsytRiecsaelarch Services Study Report Author: No. RG FACT-TOX-111, York et al. July 23, 1999. OTHER Dra iidsss por Append V -- Bb N vss 000359 ROBUST SUMMARY- RS53 `Title: Determinationof Fluorochemicals Serum Hal-Livesof Perfluorooctancsulfonate and Other TEST SUBSTANCE Identity: PFOS Remarks: METHOD S1t9u98d)yfdreosmig2n:7 rCeotlirleedc,tfalnudoraoncahleymziecsalerpurmodeuvcetriyonsiexmmpolnotyhesesfoirnourpdteortyoeadrest(ebremgiinnentihnegsNeorvumemhbalefrlife ofPFOS and other fluorochemicals Manufacturing/Processing/Use: N/A Hypothesis tested: Determine serum half-life ofPFOS and other fluorochemicals. Study period: 1998-2003 Setting: N/A mTaontuaflapcotpuurliantgiosint:es.27 refirces from 3M Decatur (n = 24) and Cottage Grove (n = 3) Subject selection criteria: Not provided in report. `Total #of subjects in study: N =24 Comparison population: N/A Participation rate: 100 percent,to date rSeutbijreeectwadses6c0riypetairosn:(ra2n5gema5l5e-a7n4d y2eafrse)m.aleMereatnireneus.mbAesrooff mbeognitnhnsinfgroofmstruedtiyr,emaevnetratgoethaegestoarft of the study was 30 months (range 5 - 130 months). Health effects studied: None Data collection methods: Blood scra samples TDhetraeielscoolnledctaitoanscohlalveectoicocnu:rrBeedg,itnonidantge,inacNcoovredmibnegrt,o t1h9e981*bilnotoedriims croeplolretc.tedNoevienrfyosrimxatmioonnthwsa.s Drproovindieldsasssto hoRewpotrtheAbplpoeondd was drawn, stored, analyzed, ete. vas 000360 Exposure period: Unknown. eDxepsocrsiuprteitoon/fdleuloirnoecahteimoincoaflsexposure groups/categories: Retirees with prior occupational Measured or estimated exposure: N/A Exposure levels: N/A `Stmaotnitshtiicnatlermvealtsh)oadsss:umSienrguamohnaelf-cloimfpeacratlmcuelnattaeld mboadseeld.on three data points (approximately six Other methodological information: RESULTS ODfesPcFrOibSewraessul3t4s4: dIanyistiaflorse2r0ummaPleFOanSdlfeevemlalrearnegteidreefsrowmho0s.1e-lo3.g1lipnpcma.r reMgerdeisasinonsemroudmelhahlafdliafen > 0.6. Neither age nor calculation for PFOS. the number ofmonths retired was associated with the serum half-life sSttuudyd.y sItnrteenrgitmhrsepaonrdtswweialklnbeessiesssu:edTehviesriys stihxemfiornstthisnt(earfitmerrecpaocrhtonfewthdisatsaecroulmlePctFiOonS).haRlef-sluilftes ssuhbojuelcdtsbeweirnetenroprterteepdocratuetd;iosusolmyedbueectaoustehethpeayucdiitdyonfotdayteta haavvaieltahbelierttohidradted.atSaepvoeinnotfantdheot2h7ers becauseofthe lack of fitofthe linear model. Research sponsors: 3M Medical Department Consistency of results: N/A CONCLUSIONS Na REFERENCE Interim Report #1. Company: St. Paul, Determinationof June 8, 2000. Serum Half-Lives of Several Fluorochemicals. 3M OTHER Dra nil AsesmensRepors Append V vas 000361 ROBUST SUMMARY- RS54 "Title: 28-Day Percutaneous Absorption Study with FC-95 in Albino Rabbits (1981) TEST SUBSTANCE Identity: Potassium perfluorooctanoic acid, CAS 2795-39-3 Remarks: FC-95 METHOD Method/guideline followed: NA Test type: in vivo Species/strain/cell type or line: rabbit, New Zealand White Sex: male and female Age and body weight range of animals used: 1.82 2.37 kg (Nduefmibnietriveo)f animals/sex/dose: 2 male and 2 female (range-finding); 10 male and 10 female Route of administration: dermal (approximately 40%of body surface area) Vehicle: None specified Doses: Single (definitive) doses of 1,000 and 5,000 mg/kg (range-finding); Single dosesof 5,000 mg/kg fEoxrcrseetriuomntraokuetnesf,robmodreytrfol-uoirdbsi,taalnsdintuissspureisormotonidtosoirnegdaanndd/oonrdsaaysmp1l,e7,d 1d4urainndg2s8tuafdtye:r bdlosoiondg. Statistical methods used: Not specified tMheetihntoadctrsekmianrtkosc:ovTehreaptprurnokxoifmcataeclhy r4a0bb%itofwatshecslkiipnpesdurffraeceeofarheaa.iraInmdpetrhveiotuesstpalratsitcilce pshleaecteidnogn twhaast aunsiemdatlosomcaclyuddiestthurebtetshteaarptpilcilec.atiAon.flexAifbtleerp2l4asthiocurcsoollfarcwonatsacuts,etdhetotemsitnmiamtierziealthweapsossibility ardemmionvisetdraftrioomn,tahte osnkien.anAdntiwmoalhsouwresrpeosotb-sdeorsvee,dafftoerrprheamromvaaclootfoxtihce stiegsntsaritmimcleediaantdedlayilayfter stthuedrye)a.fieIrnutnhteildtefeirnmiitniavteisotnu(d1y,4 bdlaoyosdfworasthoebrtaanignee-dfifnrdoimngthseturdeytrao-nodrb2i8tadlasyisnufsorfotrhesedrefuimniatniavleysis trprhaietodrneif(a0ilnaisptepislvsiemcseattsuiRdoeynp,oratbnodAdpoypnewdidecaiygsht1s,7w,e1r4earnedco2r8depdositn-idtoisalilnyg.andSeornudmawysas7,fr1o4zaenndfo2r8.anaGlryosisss. In Vie 000362 necropsy was performed on day 28. RESULTS Ddeeftianiilteivdersetsuudlyt.s:HyNpeoradcetaitvhistwyewraesobnsoetrevdeadmaotnagny5 doofs1e0imnabloetshotnhedraaynsg6e-afnindd7inpgosstt-uddoysianngd. thNeo vOinsliyblseelreusimonfsrowmertehenodtaeyd1atanndecdraopysy2.8 bOlnooedmdarlaewhsafdrwoemiognhet lmoaslsenaonteddoantetfheemeanldeorfabtbhietswteurdye. arensapleyczteidv.elyF.emMaalleeddaayy1 1aannddddaayy2288sseerruummtottoatlalflfulouroirnienelleevveellsswweerree0.190.a3nadnd1281.300.p2ppmp,m, respectively. Metabolites measured: Total fluorine (assumed to represent perfluorooctane sulfonate) CONCLUSIONS `The dermal LD, is greater than 5,000 mg/kg. Nthoe dfaecftintihtaitveabcsoonrcpltuisoinonasppceaanrsbetodorcacwunr.from the pharmacokinetic phase of this study other than REFERENCE O'Malley, K. D. Albino Rabbits, and Ebbens, K. L. Safety Evaluation L(a1b9o8r1a)to2r8y,DRaiykePrerLcaubtoraanteooruisesA,bsIoncr.p,tEixopneSrtiumdeyntwiNtoh. FC-95 in 0979AB0632. OTHER `1T0hiesstwaablsisnhotthaeGlaLcPkosftsuidgyn;ihfoicwaenvterd,erimt awlastoaxuicdiittyedfrboymtshienQglAe Uappfluincctaitoino.n oTfhaelsatrugedydoissea.deTqhuaete study is not adequate in providing useful information on the dermal absorption of PFOS. [-------- vam 000363 ROBUST SUMMARY - RS55 Title: Oral Teratology Studyof T-2999CoC in Rabbits TEST SUBSTANCE Identity: Lot FM 3924. Remarks: Identified as "wide-range" N- Ethyl FOSE alcohol in an internal 3M memo from DR Rickerto WC MCCormick dated December 10, 1980. Wide range was given to be: 88%C,F ;SO,N(CH,CH,)CH,CH,0H 10% C,,C, and C,-F,n,, SO,N(CH,CH,)CH,CH,0H, 1% N-Ethyl amide and 1% high boiler. METHOD Method/Guideline followed: Complied with general recommendation ofthe US FDA issued in January, 196.6 "Guidelines for Reproduction Studies for Safety Evaluationof Drugs for Human Usage." `GLP: Yes. Stated to be conducted in compliance with the FDA 1978 Good Laboratory Practice Regulations. Year study performed: 1981 Species/Strain: Rabbit, New Zealand White/Miniken from Dutchland Laboratories. Number of animals per dose: Rangefinder study, six. Principal study, eighteen Route of administration: Oral (intubation) Dosing regimen (list all with units): Does were dosed at a constant volume of 1 ml/kg, once daily, on gestation days (GD) 6-18 (day 0). The vehicle was com oil. Doses: Rangefinder: 0, 6,9, 12, 15, 25, 50, 75, or 100 mg/kg bodyweight. Principal study: 0, 1.5, 5, 15 mg/kg bodyweight Statistical methods used: Dunnett's t test for dam and pup weights, numberoffetuses, number ofresorption sites, numberof implantation sites and numberof corporea lutea. Chi square for percent abnormalities. RESULTS NOAEL: Matemal 5 mg/kg. Developmental 5.0 mg/kg. TM 000364 LOAEL (dose and effect~) maternal and developmental: Maternal. 15 mg/k-g reduced terminationofthe study. mean body weight gain commencing with dosing through Developmental period. 15 mg/kg abortions, total resorptions, poor survival during 24 hour incubation `Toxic responseleffects by dose level - maternal: aRanndgesfiignndsoefr.abDorotsieosn.ofO1v0e0r, 5750,%5o0f,foerm2a5lemsg/dikegdraetsutlhteed2 hinigchoemstpoduosnedlaenvedlsd,odseeartehlsataeldsodeaths loictcteurrsrwedheatntthheelsotwuedry lweavesls.terAmlilndaatemdsaetiGthDer2a2b.orTtheedreorwwaesrealisno athmeeparoncebsosdyofwaebisgohrtblionsgstahteiarll cdoosnecse.ptIunsaes2"atrtahnegehfiignhdderossetu(d1y5 tmhge/rkegw)erweerneomcaoimntpaoiunnedd druelraitnegdpdreeagtnhasncayn.d a majorityofthe tPhrirnocuigphaolusttutdhye.dToshieng15pemrgi/odkgundtoilsetehrmaidnaatrieodnoufcetdhmeesatnudyw.eiTghhet rgeadiuncctioomnpawraesdsttaoticsotnitcraollly different during the Sor 1.5 mg/kg dose. GD 6-9 period. There were io compound related maternal effects seen at the m`Tgo/xkicgraessepvonisdee/necfefdecbtyssbtaytidsotisceallleyvsei-glnidfeivcealnotpimnecnrteaalse.s Einmbrreysootrpotxiiocnitayndwadescorbesaesredvevdiaabtle15 ffeettuusseess.eTxhpeernieunmcbeedrpofoiomrpsluarnvtivaatliodnursiintegs,thceor2p4ohraoulrutienacaubnadtifeotnalpewreiiogdh,t1w4a/2s8nvost a1f6f/e8c1tedi.n cTohnterol (p<0.03)." related. No gross, internal, or skeletal malformations were considered to be compound `There were no compound related fetal effects seen at the 5 or 1.5 mg/kg dose. Statistieal results: Statistically significant results discussed above. Remarks -- Additional information to adequately assess the data: None. CONCLUSIONS Comment on conclusions. author's conclusions and whether you agree: Agree with the study author's REFERENCES Report: St. Paul Oral MN. Teratology Studyof T-2999CoC in Experiment Number 0681TB0212. Rabbits, January 7, 1982. Riker Laboratories, LRaebpoorratt:orOireasl,RSat.ngPeafuilndMeNr.StEuxdpyeorifmTe-n2t9n9u9mCboeCri0n6P8r0eRgBna0n0t19Rabbits, June 25, 1981. Riker of niaAsssmen Report Appests van 000365 ROBUST SUMMARY - RS56 Title: Absorption and biotransformation of N-EFOSE and tissue distribution and elimination of carbon-14 after administration of N-EtFOSE-""C in feed (1983) TEST SUBSTANCE Identity: 2-N-ethyl perfluorooctanesulfonamido ethanol labelled with carbon-14 at the carbon alpha to the sulfur atom (Riker Isotope Inventory Number 468, 0.483 0.020 uCi/mg) Remarks: FC-95-14C (carbon-14 label alpha to sulfur atom, Riker Isotope Inventory Number 442). The specific activity is 0.459 +- 0.008 uCiimg. Thin-layer and column chromatography showed the FC-95-14C to be at least 99% radiochemically pure. The FC-95-14C was found to be suitable for metabolism studies. (Synthesis described in Johnson and Beh, 1979). METHOD Method/guideline followed: NA Test type: in vivo Species/strainicell type or line: rat, Charles River CD Sex: male Age and body weight range of animals used: weeks, bw mean 277 g (range 220-329) Number of animals/sex/dose: 3 per each time-point experimental group (only one dose used) for time points 1,2,4,8,16 and 32 days post-dose. Route of administration: dietary, mixed in feed, given to fasted rats for two hours (time-point `groups for 1,2, and 4days) or 12 hours (time-point groups for 8,16 and 32 days) Vehicle: feed only Doses: 0.531 mg/g feed (531 ppm in diet) given as a single "dose" to fasted rats with a mean dose of 10.13 mg/kg as calculated from the weightoffeed consumed Excretion routes, body fluids, and tissues monitored and/or sampled during study: Urine and feces (continuous 24-hour collectionsfor time-points 1,2,4and 8 days and pooled collections for each animal in time-point groups for 16 and 32 days). Tissues and fluids taken at terminal sacrificeofeach group were blood/plasma, liver, kidney, lung, spleen, bone marrow, subcutaneous and abdominal fat, and muscle (all animals), as well as digestive tract (esophagus, stomach and intestines) and remaining carcass (time-point groups for 1 and 2 days post-dose). ref nitsre Report ppenic vars ov366 Statistical methods used: mean, standard deviation Method remarks: Rats were fasted with free access to water for 24 hours prior to dosing. Groupsofthree rats for each time point were assembled such that their individual body weights did not differ by more than 21 grams. The diet/test compound mixture was provided for two hours to animals in the groups for 1,2 and 4 days. All feed was consumed in this period. For animals in tme-point `groups 8,16 and 32 days, feeding was allowed for 12 hours; however, mostofthe feed was immediately consumed. Dose was verified by analysis ofthe feed/test compound mixture and by weighing the amountoffeed consumed. The authors note that very little feed was spilled. RESULTS Detailed results: `The authors conclude that at least 70 %of the dose administered in feed was absorbed. Elimination in urine was concluded to be poor, with less than 3.0 %ofthe dose being eliminated in urine by 32 days post-dose. Fecal elimination was 20-30 times more extensive than urinary elimination, with approximately 60 %ofthe dose being eliminated in 32 days. Total recovery of radioactivity over 48 hours was 86 %. A meanof9.5 %of the dose was in the liver after 32 days. After 32 days, the mean liver/plasma, spleen/plasma and bone marrow/plasma ratios were 11.8, 0.4 and 0.4, respectively. Liver to plasma ratios increased rapidly to plateau after 16 days. `The serum elimination half-life was found to be 7.5 days over the first 16 days; however, there was practically no change in the serum concentration from day 16 to day 32 (2.2 pg equivalents versus 2.1 pug equivalents at day 32). Perfluoroctanesulfonate (PFOS) was identified as a `metabolite in the liver extractsofrats sacrificed at 48 hours post-dose. PFOS represented at least 22 %ofthe radioactivity found in the liver at 48 hours. Perfluorooctanesulfonamide was tentatively identified as another metabolite in the 48-hour liver extracts. This metabolite, assumed to be perfluorooctanesulfonamide, represented at least 32 %of theradioactivity found in the liver at 48 hours post-dose. Other metabolites were present but not identified. `The distributionofcabon-14 in tissues over time is represented by the following table. Data are expressed as a percentof dose in tissue. Drath nial sscsmers Report Append V van 000367 Table. Carbon-14 content oftissues after an oral dose of N-EtFOSE-"C in feed to male rats (mean dose, 10.13 mg/kg) Bay Post Liver Kidney| Lungs |RBC GI Carcas 12[f7o%o [[aanns JJoosst [[oodasr[[570090 [[22582 [[Treaeil[[10587 || OIEC 2 XE0 OE T 3 C ECO 5OE EBEELL [6 {106sToe [o0 a JCorC oCsXs [CooEr [E WW E| ((ba)) Estimate Sample not taken Metabolites measured: Perfluorooctanesulfonate identified and quantitated. Perfluorooctanesulfonamide tentatively identified. CONCLUSIONS The study is well-conducted and thorough. Agree with the conclusionsofthe authors. REFERENCE Extent and Routeof Excretion and Tissue Distribution of Total Carbon-14 in Rats after a Single Intravenous Dose of FC-95-14 C. Riker Laboratories, Inc., Subsidiary of 3M, St. Paul, MN. Johnson, JD, Gibson, SJ, and Ober, RE , December 28, 1979. Ong HoT vay 000368 ROBUST SUMMARY - RS57 Title: Extent and RouteofExcretion and Tissue Distributionof Total Carbon-14 in Rats after a Single Intravenous DoseofFC-95-14C (1979) TEST SUBSTANCE Identity: FC-95-14C, Carbon-14 labeled potassium perfluorooctylsulfonate, CAS 2795-39-3 Remarks: FC-95-14C (carbon-14 label alpha to sulfur atom, Riker Isotope Inventory Number 442). The specific activity is 0.459 +- 0.008 uCi/mg. Thin-layer and column chromatography showed the FC-95-14C to be at least 99% radiochemically pure. The FC-95-14C was found to be suitable for metabolism studies. (Synthesis described in Johnson and Behr, 1979). METHOD Method/guideline followed: NA Test type: in vivo Species/strain/eell type or line: rat, Charles River CD Sex: male Age and body weight range of animals used: weeks, bw mean 288 g (range 262-303) Numberof animals/sex/dose: 6 Route of administration: iv, via tail vein Vehicle: 0.9% NaCL solution containing 1.2 mg FC-95-14C/2.0 ml Doses: 4.2 mg/kg average, single dose Excretion routes, body fluids, and tissues monitored and/or sampled during study: urine, feces, liver, plasma, kidney, lung, spleen, bone marrow, adrenals, skin, testes, muscle, fat, eye, brein Statistical methods used: mean, standard deviation Method remarks: Rats were conditioned to individual metal metabolism cages for 24 hours prior to dosing. The rats were allowed free access to Purina Ground Chow and water before and after dosing. Each rat was weighed, anesthetized with diethyl ether, then given a single iv dose using a 3.0 cc disposable plastic syringe fitted with a 26 gauge 1/2" needle. Urine and feces were collected at Dra ntlsess Report Append va 000369 intervals for each of the six rats for 89 days. At 89 days post dose, the rats were anesthetized with diethyl ether; blood was drawn from the descending aorta, animals were sacrificed by exsangination, and tissue samples were collected. RESULTS Detailed results: By 89 days post dose, mean urinary excretion was 30.2+-1.5%oftotal C-14 administered. Mean cumulative fecal excretion was 12.6+-1.2%. Radioactive content in feces was 00 low to `measureafter64 days. Mean tissue C-14 concentrations above one ug FC-95-14C equivalents/g were as follows: liver, 20.6; plasma, 2.2; kidney, 1.1; and lung, 1.1. Other tissues such as `muscle, skin, bone marrow, and spleen had concentrations ranging from 0.2 0 0.6 ug/g. There was a difference in C-14 contentof subcutaneous fat (0.2 ug/g) and abdominal fat (<= 0.08 ug/g). Very little C-14 was found in whole eye (0.16 ug/g) and no detectable C-14 was found in brain. Only liver and plasma contained a substantial percentageofdose at 89 days post dose, 25.21% and 2.81%, respectively. The low levelsofradioactivity found for kidney, lung, testes, and spleen are due in part to blood still contained in these organs when homogenized. Mean Excretion of Total Carbon-14 in Urine Over Time Collection Period Percent Dose (Days) During Period 00.5 091 05-1 077 12 121 23 1.03 34 093 45 083 56 07 67 076 78 075 89 0.68 9-10 0.68 10-11 0.59 11-12 0.58 1213 059 13-14 055 14-15 054 15-16 051 16-17 048 17-18 043 18-19 : 039 19:21 084 2123 0.78 23.25 0.66 2527 0.68 2729 068 2932 086 Dra itl Assn:Report Appedic "500370 32:36 1.05 36-40 099 40-43 075 4347 092 47-50 0.68 50-54 078 5457 0.61 57-61 079 61-69 1.50 69-78 1.64 78:89 2.08 Total 302 Mean Excretionof Total Carbon-14 in Feces Over Time Collection Period Percent Dose (Days) During Period, 00.5 0.049 05-1 0.842 12 0.795 23 0.649 34 0.656 45 0577 56 0510 67 0.588 78 0.482 89 0.421 9-10 0.387 10-11 0370 11-12 029 12:13 0310 13-14 0281 1415 0276 15-16 0272 16-17 0.187 17-18 0.163 18-19 0.129 1921 0311 21-23 0302 23.25 0262 2527 0208 27.29 0202 29-32 0223 32:36 0526 36-50 1530 50-64 0833 Total 126 -- "7 000374 Metabolites measured: none. CONCLUSIONS agree REFERENCE Extent and Route of Excretion and Tissue DistributionofTotal Carbon-14 in Rats after a Single Intravenous Dose of FC-95- 14 C. Riker Laboratories, Inc., Subsidiaryof3M, St. Paul, MN. Johnson, JD, Gibson, SI, and Ober, RE , December28, 1979. OTHER DropnilAsessmReepnorst - Append vam 006373 ROBUST SUMMARY - RS58 Title: Cholestyramine-Enhanced Fecal Eliminationof Carbon-14 in Rats after Administration `of Ammonium [14C]Perfluorooctanoaotre Potassium [14C]Perfluorooctanesulfonate (1984) TEST SUBSTANCE Identity: Potassium [14C]Perfluorooctanesulfonate (14C-PFOS) Ammonium [14C]Perfluorooctanoate (14C-PFO) Remarks: 14C-PFOS: sp act 0.46 uClmg, radiochemical purity >99%, 14C label in PFOS is adjacent to sulfur 14C-PFO: sp act 0.51 uClmg, radiochemical purity >98% METHOD Method/guideline followed: NA Test type: in vivo Species/straincell type or line: rat, Charles River CD Sex: male Age and body weight range of animals used: 12 weeks, 300-342 g Number of animals/sex/dose: 5 Route of administration: iv Vehicle: 0.9% NaCl, 2 ml/rat Doses: Potassium [14C]Perfluorooctanesulfonate (POS): 3.4 mg/kg mean, single dose, 0.56 mg/ml PFOS control animals: 3.5 mg/kg mean Ammonium [14C)Perfluorooctanoate (PFO): 13.3 mg/kg mean, single dose, 2.1 mg/ml PFO control animals: 13.5 mg/kg mean Excretion routes, body fluids, and tissues monitored and/or sampled during study: Urine, plasma, red blood cells, liver Statistical methods used: mean, standard deviation, Student's test Method remarks: rReatfsnwiearAeshaounseRdepionrtinAdpipevniddual stainless-steel metabolism cages and fasted with free aVcciesss to 000373 `water for 24 hrs prior to receiving the fluorochemicals. The radiolabeled compounds were administered as single intravenous doses (lateral tail vein). Two mlofdosing solution was administered to cach rat. Ten rats were dosed with each compound. Five rats from each group `were fed cholestyramine (dried and ground resin Z-620), 4% in feed (Purina Lab Chow), for 14 days after administration ofPFO andfor21 days after administrationof PFOS. Control rats `were administered radiolabeled fluorochemical but were not treated with cholestyramine. In order to allow comparisonofthe radiometric results on an absolute basis, the radiolabel doses were not adjusted for individual body weights. Urine and feces samples were collected at intervals for individual rats in each group until 14 days after 14C-PFO administration and 21 days after 14C-PFOS administration. At these times, rats were anesthetized with diethyl ether and exsanguinated by drawing blood from the descending aorta. Plasma and red blood cells were prepared promptly by centrifugation. Liver was collected as the whole organ and stored frozen until analysis. RESULTS Detailed results: After 21 daysofcholestyramine treatment, the mean percentage of 14C-PFOS dose eliminated via feces (75.8 +- 5.0) was 9.5-fold the mean percentageofdose eliminated via feces by control rats (8.0+ 0.8). After adjustment for the amountofcarbon-14 excreted in urine (18% for controls and 5% for cholestyramine-treated), the amountsofcarbon-14 remaining to be excreted are 19% for cholestyramine-treated rats and 74% for control rats. Afier 14C-PFOS administration, the mean liver carbon-14 content at 21 days represents 11% and 40% of the dose forcholestyramine treated and control rats, respectively. Mean plasma and red blood cell carbon-14 concentrations are significantly lowerafter21 daysofcholestyramine treatment. After 14 daysofcholestyramine treatment, the mean percentage of 14C-PFO dose eliminated via feces (43.2 + 5.5) was 9.8-fold the mean percentageofdose eliminated via feces by control rats (44+ 1.0). After adjustment for the amountofcarbon-14 excreted in urine (67% for controls and 419% for cholestyraminetreated), the amountsof carbon-14 remaining to be excreted are 16% for cholestyramine-treated rats and 28% for control rats. After 14C-PFO administration, the mean liver carbon-14 content at 14 days represents 4% and 8%ofthe dose for cholestyraminetreated and control rats, respectively. Mean plasma and red blood cell carbon-14 concentrations are significantly lower after 14 daysof cholestyramine treatment. Carbon-14 Concentration (expressed as ug eq/g tissue or ml fluid) Treatment Group Liver Plasma Red Blood Cells 14C-PFOS Cholestyramine ~~ 9.4+-16* 09+0.1* 0340.1 Control 356456 69+06 18+0.4 14C-PFO Cholestyramine~~ 12.1+2.1% Control 23+62 5.1+-1.7* 147+638 18-07 42424 *Significantly different from control values (p<0.05) rpntl Ascsmens Roepoort Appendic vas 00374 . `The authors conclude that the high concentration of 14C-PFOS or 14C-PFO in liver at 2 to 3 weeks after dosing and the fact that cholestyramine treatment enhances fecal elimination of carbon-14 by nearly 10-fold suggest that there is a considerable enterohepatic circulation of 14CPFOS and 14C-PFO. Metabolites measured: none CONCLUSIONS agree REFERENCE Johnson, J. D., Gibson, SJ, and Ober, RE (1984). Cholestyramine-Enhanced Fecal Elimination of Carbon-14 in Rats after AdministrationofAmmonium [14C)Perfluorooctanoate or Potassium [14C]Perfluorooctanesulfonate. Fundamental and Applied Toxicology 4, pages 972-976. OTHER Seealso Johnson, J. D., Gibson, SJ, and Ober RE (1984). Enhanced eliminationof FC-95-14C and FC-143-14C in rats with cholestyramine treatment. Project No. 8900310200, Riker Laboratories, Inc. St. Paul, MN. Dr ntissn Rpor- ppeic vas 000375 ROBUST SUMMARY - RS59 `Title: Analytical Laboratory Report on the Determinationofthe Presence and Concentration of Potassium Perfluorooctanesulfonate (CAS Number: 2795-39-3) in the Serum and Liver of Sprague-Dawley Rats Exposed to PFOS via Gavage (1999) TEST SUBSTANCE Identity: Potassium Perfluorooctanesulfonate (PFOS), CAS Number: 2795-39-3 Remarks: PFOS purity 99.28%, 3M Chemical Lot Number 193 METHOD Method/guideline followed: US FDA GLP Final Rule 21 CFR 58 Test type: in vivo Species/strain/cell type or line: rat, Sprague-Dawley Sex: both Age and body weight rangeof animals used: 60 days, males 300-325 g, females 200-225 g Number of animals/sex/dose: FO 35, F125 Route of administration: oral Vehicle: 0.5% Tween 80, 5 ml/kg Doses: 0.1, 0.4, 1.6, or 3.2 mg PFOS per kg/day in 0.5% Tween 80. These doses correspond to concentrationsof 0.2, 0.8, 0.32, and 0.64 mg/ml. Groups of vehicle control FO rats were administered only Tween 80. Male FO animals were treated 42 days prior to mating and through `mating period; female FO animals were administered PFOS daily 42 days prior to mating, through gestation, and up to 20 days following litter delivery. FI male and female rats were `exposed to the chemical in utero and during lactation. Following weaning at 21 days ofage, selected F1 animals were treated during development and productionof F2 animals. Elixvcerreatnidonserrouutmes, body fluids, and tissues monitored and/or sampled during study: Statistical methods used: Means and standard deviations were calculated using Microsoft Excel, and relative standard deviations were calculated manually. ort Annger pnd vadmooa7e Method remarks: Liver and sera samples collected from the initial populationof dosed animals (F0) and their offspring (F1) were analyzed for the presence ofPFOS. Liver samples were homogenized, and liver and sera samples were extracted by an ion-pairing extraction procedure. The extracts were quantitatively analyzed using high-pressure liquid chromatography/electrospray tandem mass spectrometry, and PFOS levels were evaluated against extracted standards. Some minor deviations from US FDA GLP Final Rule 21 CFR 58 are listed in the report RESULTS Detailed results: FO results by dose group: Dose group Average PFOS conc. (mgkg/day) in serum (ug/ml) 00: female 0.0307 male 0.0244 0.1: female 5.28 male 10.5 0.4: female 18.9 male 45.4 16: female 82 male 152 32 female NR* male 273 *samples not received Average PFOS conc. in liver (uglg) female 0.171 male 0.665 female 14.8 male84.9 female 58.0 male 176 female 184 male 323 female NR* male 1360 Average PFOS concentrations in pooled liver samples from F1 animals shortly after birth were 0.0511, 6.19, 57.6, and 70.4 ug/g in the 0.0, 0.1, 0.4, and 1.6 mg/kg/day dose groups, respectively. No samples collected from F1 males or females that received 3.2 mg/kg/day were submitted for analysis. Metabolites measured: Analyses were performed to determine the presence of EIFOSE, PFOSA, POAA<PFOSEA, PFOSAA, and the monoester; however, these data were collected for informational purposes only, and were not reported. CONCLUSIONS: agree REFERENCE Analytical Laboratory Report on the Determinationof the Presence and Concentration of Potassium Perfluorooctanesulfonate (CAS Number: 2795-39-3) in the Serum and Liver of Sprague-Dawley Rats Exposed to PFOS via Gavage. Argus Research Laboratories, Inc., Horsham, PA. Laboratory Report No. U2006, Requestor Project No. 3M TOX 6295.9, 3M Environmental Laboratory Report No. FACT Tox-012. York, RG, Hansen, K, and Clemen, L., October 27, 1999. OTHER Dra ntlsesResport Append V vi900377 raf nil Assesment Repor Append V14000378 ROBUST SUMMARY - RS60 Title: Absorption of FC-95-14C in Rats after a Single OralDose (1979) TEST SUBSTANCE Identity: FC-95-14C, Carbon-14 labeled potassium perfluorooctylsulfonate, CAS 2795-39-3 Remarks: sFpCe-ci9f5i-c1a4cCtiv(ictayrbison0-.14459la+b-el0a.l0p0h8atuoCi/smuglf.urTahtionm-,laRyiekrearnIdsoctoolpuemInnvcehnrtoomraytNougrmabpehry 4s4h2)o.weTdhtehe FC-95-14C 10 be at least 99% radiochemically pure. The FC-95-14C was found to be suitable for metabolism studies. (Synthesis described in Johnson and Behr, 1979). METHOD Method/guideline followed: NA Test type: in vivo Species/strainicell type or line: rat, Charles River CD Sex: male Age and body weight range of animals used: weeks, bw mean 285 g (range 243-315) Number of animals/sex/dose: 24 Route of administration: oral Vehicle: 0.9% NaCL solution containing 1.2 mg FC-95-14C/2.0 ml Doses: 4.2 mg/kg average, single dose: rEexdcrbeltoioodncerlolust,epsl,absmoad,yufrliunied,s,feacnesd, tsipslseueens, mdiogneisttoivreedtraacntdp/loursscaonmtpelnetds (deusroipnhgagsutsu,dys:tomach, small intestine, large intestine, and colon), and carcass Statistical methods used: mean, log mean concentration versus time least squares line Method remarks: Rats were conditioned to individual metal metabolism cages for 24 hours prior to dosing. Rats wfaesrteedarlaltowwaeds fwreeiegahcecdesismtmoedPiuartinealyGrbeofuonrde Cbehionwg gainvdenwaatesirnbgelfeoorrealanddosaefotefr FdCos-i9n5g-.14ECa.chTnhoen- dhoalsfinhgousrolauttmioondewraasteprseppeaerdedinbaymaedcdhianngi~ca2l00shmakgeorf, aFnCd-9ce5n-t1ri4fCugtion0g..9T%heNasCulpe,rsnahtaaknitngwafosr one rat iil Assn Ror ppendicV vase 000379 rdeetmeorvmeidneadndbyusdierdecftorcoduonstiinngg.solTuhteiond.osTehewacsardbeolni-ve1r4ecdownittehntaof2t.0hce dgolsaisnsgssyorliuntgieon(Twraylson) fitted with a stainless steel intubation tube. `poGsrtoudpossoef.thRraetes rwaetrseweanreestsahcertiifziecdedwibtyhedxiseatnhygluientahteiroannadtb1l,o2o,d6,wa1s2,d2r4a,w4n8,fr9o6,m atnhed d1e4s4cehnoduirnsg aortaofeach rat and by centrifugation. In imediately transferred to a heparinized tube. addition toplasmaand red blood cells, otal Plasma was prepared promptly urine, total feces, spleen, driegmeasitnidveertroafcctarplcuassscownetrenetssa(veesdopfhraogmuse,acshtoofmatchhe,tshmraelelraitnsteisntitnhee,2l4aragendin4te8sthionuer,sapnodsctodloons)e, and `groups for carbon-14 analysis. RESULTS Detailed results: Arafttse,raat lseiansgtl9e 5or%aolfdtohseeotfotaFlC-ca9r5b-o1n4-C14(msesaynstdeomsiec,a4l.l2y magb/sokrgb)eidnasto2lu4thioounrtso.gTrohuephsoalfft-hlirfeeefomrale eliminationoftotal carbon-14 from plasma is 7.5 days. `eTxhceredtiigoenstiisv1e.t5ra5c%toafndthceondtoesnetsatc2on4thaoiunresd aonndt3he.2a4ve%raagte4,83h.o4ur5s%.oftAthe24dohsoeu.rs,Ththeemmeeaannfsecuaml of tloitkaellycarrepbroens-e1n4tsinsyfsetceemsiacnaldldyiagbesstoirvbeedtraccatrpblouns-1c4onptreenstesntisc5it%hoerftinhethedodsieg.estSiovmeetorfactthtiisss5ue%s or in of the digestive tract rats are consistent contents with the as 24 a resultofexcretion. hour post dose data. The data from the 48 hour post dose Thus, at least 95%ofthe FC-95-14C group dose wraadsioaabctsiovribteydrfercoovmesroeldutwiaosn fafotuenrdadinmitnhiestcarractaisosn. toTnhoen-cfaarsctaesds draattsa. aTrehenomtaajsorreploiratblieonoasftthheeother twiasssudeifdfaitcaulstintcoeaslsaurrgee.voThleurmee ihsosmoomgeeneaxtcerestwioenreofnetocteaslscaaryrbaonnd-1h4ominoguerinnceit(y1o-2f%/sdaamyp)l.e Talhiequots asnpldeetnhse pferrocmentthoef24thheoduorsaenidn4t8hehwohuorlpeosotrgdaonsewraasts~w0e.r2e%.anTahlyezceodncfeornttroatatliocnasrobfotno-t1a4lccoanrtbenotn,14. icnonrceedntbrlaotoidoncealtls24anadndpl4a8smhaouwresries c0o.m2p5aarnedd.0.3T9h,eremsepaecntirvaetliyo.ofrTheuds,blaot o2d4 caelnld t4o8plhoausrmsa aflera single oral dose of FC-95-14C, there is no selective retentionof carbon-14 in red blood cells; `gTrhoeuphasloff-tlihfreoefe eraltismiatna1t,i2o,n6f,r1o2m, p2l4,as4m8a, w96a,sadnedte1r4m4inheodurbsyaaftnearlyasissiongflpeloarsalmadossaeompfleFsC-f9r5o-m l1i4nCe.thTrhoeuglhogtohefimnediavnidcuoanlcpeonitnrtastifornovme2rs4ustoti1m4e4 hfoorurtshefsoerdtahteasewadastpaloftittsedt.heTehqeuatleiaosnt:sCqpua=res i1s5.16759h(o-u0r.s00(37.8571d)aywsh)e.reThCups, ies lpilmaisnamtaicoonncfernotmraptlioans.maTohfetohtaallf-claifreboonfe-l1i4maifntaertiaonsinfgrloemoprallasdmoase Of FC-95-14C is slow. Metabolites measured: none CONCLUSIONS agree Dra itl Assesment Repors Append V : var 000380 REFERENCE `Absorption of FC-95-14C in Rats after a Single Oral Dose. Riker Laboratories, Inc., Subsidiary of 3M, St. Paul, MN. Project No. 890310200. Johnson, JD, Gibson, SJ, and Ober, RF, October 26,1979. OThTisHEorRal dosing experiment (FC-Experiment 4) was paired with an iv dosing experiment (FCExperiment 3) which was designed to provide data on the route and extentoftotal C-14 excretion. Dv miiAssent Report Append "$o0as1