Document 2wGdxOoG7p9JRO1ZJBa0Y56r

`Toxicological Summary PFOS Dietary Chronic Pilot Reproductive Study: Mallard Test Substance: Perfluorooctanesulf(oPnFaOtSe) Structure: p1o-tOacstsanieusmuslaflot,niCcAaSci#d,2719,51-23253..3344,55,6,6,7,8,88-hepladecafluoroTest Remarks: sTthoereedstunsduebrstaamnbcieenistacwohniditteiopnos,wdaenrdp(u3riMtyLowta#s2d1e7t)e.rTmhineesdam{p0bleew8a6s.9% by LC/MS, "H-NMR,andclemental analysis techniques. METHODS Method: ASTM Standard E1062-86and FIFRA Subdivision E, Section 71-4, Type: Dictary Reproduction `Year: 2000-2001 ine phase, 2000-2001 analytical phase, Final Repion2r00t3 `Species: Mallard (4nasplatyrhynchos) cEoxnpceernitrmaetnitoanls odfesi18g,n6:.2,Aodrul1t7.6maplplamrdfsorwaepreerioedxpofossiexd w1e0ek.PFCOoSncuirnretnhtely,diaetcoanttronlogmrionuapl wmaalslamradisntfarionmedaolntarenaotnm-etnrteagtreodufpeseda.ndAtfhee1i.x8 awnedek6s.o2fpepxmpostrueraet,mebnltosodvewraesecuotlhlaencitzeeddfarnodm sthuebijrerceisdpegcrtoisvse enxepcorospusrye.reTgihmeescounnttriollhaenden1d7o.f6 Wpepemktr1e9.atmAetntthgerboeugpisnwnienrgeomfaiWnetakin2ed0 othne remaining mallards were euthanized and subjected 10 a gross necropsy. Effects on adult hdeoasletsh,wbeordeytweerimgihntaalndat f6eewdeeckosn,suthmepieovanluwaetrioeneovafltuhaeteddatwaeewkalsy.divBiedceadusinetothtewtowsoeplaorwaeter analyses. The first analysis evaluated all data collected on each treme group during the first six weeksof the study. The second analysis examined data from the control and 17.6 ppm treatments collected at Wegk 20 (Table 1) Aphdoutlotstmiamlullaatridosn.werCeonbsreoquugehnttliyn,toetghgeilaryeipnrgodwuacstivineitpihataesdeapprpiroorxtiomattheeloynsoenteowfetehke satfutedrytbhye onsetofthe exposure. Egg production was evaluated on a weekly bass or the durationofthe sotiuddy.durEignggs Wlaeidedkur5inogfWethaekst| uadnyd,6woefrtehecotlelsetcwteedracnodllseecttedfoarndinacnuabaltyizoend.forRePpFrOoSd.uctEigvaes eevnadlpuoaitnetd, iinnctlhuidsincggcgggcohporrotd.uctiTohne,seemborfyfsoprviinagbilwietryehamtcahianbaiilinyc,dheoanlthn,onatnrdesautrevdivafle,edwefroer approximately 12 weeks. Necropsics were performed on offspring from cach matemal rblcaadtdmeern,taddoispeosgeroiusps.ue,SaamnpdleBsurwseareoftaFkaebnriocfiluisvefro,r bhriasitno,paktihdonleoyg,icgaolneadx,ampirnoavteinotnricfurloums,bgoatlhl 1 600347 awdeurletsthaenndaonfaflsypzriendg.forLciovnecrewnteriagthitosnswoefrePFrOeSc.orded for all ncropsied mallards, and the livers At the end of Week 6, blood samples were collected from all surviving adult birds, when possible. Following collection of blood samples, birds in the 1.8 and 6.2 ppm treatment gstrooruepdsfowrecrheemciuctahalnainzaeldysiasn.d Andedcirtoipsoineadl.bAlotodthseatmipmleesowfenreecraolpssoyc,olllievcertsedwferroemcaodlulletctbeidrdasnidn the control and 17.6 ppm treatment groups prior to euthanasia and ncropsy at the beginning oanfalWyseies.k 20P.riorAttoneeuctrhoapnsays,ialiovfterhesaomfpflseprsinwge,rbeloaolsdoscaomlplleectsewdefrreocmolaldeuclttedbifrrdosmfo1r0cohfefsmpircianlg tfrreoamtmeeancthgtrroeuaptmfeonrtagnraloyuspi.s. AdAdliltibolnoaoldlyc,oltliescstueeds ffrroomm a1d0ulotffasnpdrionfgfwsperriengcowlalsecsteepdafrraotemdeianctho serum and hemacyte/pltelt fractions "Table 1. Experimental design for the dietary chronic pilot reproductive study with mallards T(oapmm)e EPeproisod Endpoints Examined Con1t5rol 2w0eweeekk H#e1althh,isboopdaythwoelioghgty, foefedbcoodnysumoprtgiaonns,, grcoasg.s MpOrropdHuOctIiOoRny, embryo viability, hatchability, offspring health and 62 week saudruvlitvaaln,dPoRfOfsSprcionngcemnatlrlaatridosn,sPiFnOlSivecroancnedntbrlaotoidonsserinumcgogf 176 20% components (membrane, albumen, and yolk) Test Bird Age: Adult mallards (spproximately 27 weeks) Numberof Repliates: Five replicates (pens)prtreatment group Birds per Replicate: One male and female mallard per pen bFoetehdaadunldt Wmaaltlearr:dsFaonoddoaffnsdprwiantge.rFweeerdecpornosvuimdpetdioand lwiabsitmuemadsuurriendgoanllapphearspeesonfbtahsei,stoundcyetao week Analytical Monitoring: Test substance concentration in fecd,liverand serum samples were: determined by reverse-phase HPLC and mass spectrometry. Spteartfiostrimceadl tMoeetvhaoldusat:eUspigonnificcoamnptldeitfifoenreoncfetshbeettewste,eanntraneaaltymseinst ogfrovuaprsi.anDcuen(neAtNt'OsVmAu)ltiwpalse `comparison procedure was used to compare th treatment effects with control. The student's Totes was used to make statistical comparisons in those instances where only the control and the 17.6 ppm treatment groups were compared AfrvoemracgaechDapileyn Iinntatkheat(tArDeIa)tmeonftPgFrOoSupfowritehaocuhtttraekaitnmgenitntgoroauccpowuants peostteinmtaitaeldduisfifnergednacteas between the male and female paired within a pen. Food consumption and adult mallard cbaoldcyulwaetiedghatsdfaotlalowwesr:e averaged over the exposure duration of the study and the ADI was 2 R038 ADI (nggiday) =AYE`ASvereadgeCBoondsyumwpetiighotn((biOrde)y) cone tom) (Euston) "Test Diet Preparation: Test dicswerepreparedby mixing PFOS inao premixthatwasused for weekly preparationofthe est diet RESULTS aMneaalsysuersewdeDrieetcoCnodnuccetnetdrabtyioWnisl:diTfoecIonntfeimramtitohneaclonLciedn.trTahtieonlsiomiftoPfFOqSuanitnitthatidoinct(, LcOheQm)icfaolr fPeFeOdSwadusri1n.4g1Wpepem.k |Tohftehpeerscteundtyrweacsov0er.i8e7s9opfpPm.FOSDuriinntgheWemaetkri6xtshpeiLkeOdQ-iftosr rPaFnOgeSdifnrtohme 97.0 10 113% throughout the study period. Analysesofcontro dicts showed no presence of the test substance or other co-clfing compounds. PFOS. concentrations in trated feed samples ranged from 95 10 111 % of the nominal target doses. The mean measured PFOS `concentrationsfordiets detenmined in th study were: <LOQ, 1.8,6.0and 17.6ppm in feed Mortalities and Clinical Observations: No adult mortalities occurred inthecontrol or PFOS tferaetahtemrentlosgsr,outphsesdeursiinggnsthweesrteudyc.onsWidheirleed seaverreaslulmtalolfarcdaspihvaidtyhesatdreossr afonodtolrespioenmsmaantde cagagprteusrseidona.t teIstn ttehremin1a7t.i6onp.pmThtirseahtemnenatl,soonexehihbeinteadrbcoheddy hterremonresc,kraapdidbbeicnakmineg,riaginddwrhapeind respiration during the biceding process. These signs were most likely in response (0 handling nstorresmsa,lsiinncaepptheearmaanlclearadndapbpeehaarveidornotrhmraolugphroourt ftohetedsturtaetmiionnatoifont.heAsltludoy.therBamsaleldarodns twheersee. results, the dietary No observable Adverse Effect Concentration (NOAEC) for adults was 17.6 pom. AbdoudlytwBeoidgyh Wieniagdhutl: fAetmabloetsh fWreoemkan6yanodf t2h0e, ttrheeraetmweentregrnoouptsrewathmeennt-croemlpataerdedredtoucctoinolnrsolisn (fTraobmleWe2)e.k C2otmopWaerecdk t4o icnontthreol1s.,8 mthgerePFwaOsSkagsitgrneiaftimceanntt. reHdouwcetvieonr,inthifsemraeldeucbtioodnywwaesignhott consistent or dose-responsive, therefore it was not considered fo be tratment-related. In addition, there were mean body weight losses among females in the 17.6 mg PFOSke atrnedatdmaetnatvtahraitabmilaiyty,hatvheesbeedeinffreerleantceedstwoetrreeaotmtentst.atiHsotiwcealvleyrs,igdniufeictaonts.malClomspamaprleedstiozecson(tNr=ol5s), t1h1e/raewnder20e,nboosdtaytiwsetiigchatlsloy fsimganilfeicamnatllraerddusctiinontshein17m.a6lmegboPdFyOwSe/ikgghttraetaWtemeenkt w6.erBeystWateisetkica1l0l,y s1i7g.n6ifmicgantPlFyOlSesKsgthtarneatihamtenotfwthaesco1n3tr%olls.esAtthaWnetehekm2e0,anthmeamleeabnomdaylweeibgohdty iwneitghhetcoinntrtohle g`Croonucpe.ntrBaatisoend(oLnOAbEoCdy) fwoerigmhatlersedwuacstio1n7,.6tmhegdPiFcOtSar/ykeL.owSeisntceObosnelryvtahbele17.A6dvmegrsPeFOESff/ekcet treatment was conducted for the fll 20 weeks of the study, the itary NOAEC for males could not be determined. The dictary NOAEC for adult female mallards was 17.6 mg. PFOSKg 3 6005-9 Table 2. Daily exposure, feed consumpion, body and liver weight for adult mallards exposedto PFOS inthediet. Trpeamm)ent (mAgDhTgd) T(gChd) Sex Body Weigh Wook6 Weck Therw Tomol NA 22840 M TD4:71 1204297 213+470 FoOI02475 1005223 2124538 18 02695 17750 M 113678 253+156 0062 Foollasol 39804883 62 0985: 178456 M 1IS:63 2024490 176 30620513+ 24x84 MFo0o180378+505 1002004 3190245 2342802 Conan 76pp05e9s9ters wre eed WeFc_k0TO78+118459nd 8p9o7m4r1e39sme2n0t6s2w9ee5eed * Aa1cWrgeeek6D.Ayllnailkoes(aArDeIv) (nme3PsRmOeSan sbndodyawnediagddeeyv)itfiros1.a8n30dw6e.t2pwepightrboispews sdon average rTeoeudgchonWtemcpkio20n cared rough Weck6. For 17 pr tment rp. consump a versed AFterdicc onnaausdtmae atptsiisakofcensnt cWee(cpk00)fomcots. NA Nosplcbl, concentrations i diet ess haniheLOO Feed Consumption: On Weeks 14, 16, 17, 18, and 19, mallards in the 17.6 ppm treatment rheaadtmefnete.d_ coHnosuwmepvteiro,nmtahlaltarwdassinsitghneifi1c7a.6n.lypgprmeatterreatthmaenntthdaitd onfotmahlalvaerdsa icnomtehsepoconndtirnogl increase in body weight, which suggests tht he increase was the resultoffed wastage i this treatment group. Baosntehedse resus,tdhietary NOAEC was determined 0be 17.6 ppm. eLifvefr oeWenciagdthutls:t Wlihveernweciogmhptarinedantyotthreeactomnetnrtolgrgoruopu.pW,hthielreetwhreenowarasppasrteeatnitstiirccaallmyesnignriafitcaendt increase in liver weight in females from the 1.8 and 62 ppm treatments, these differences weemrmeinmaoesdt atketlhey ednudeof10Wetheekti6m,inwghoicfhthweastearmpienraitoidoonfohfigthheesgeggrporuopdsu.ctioBno.thThgerroeufposre,wetrhee minaltlhaerdlsi,verb.einBgasiendfuoln rtehpersoedurecstuilvtse,ctohndidtiieotna,rywoNuOldAEbeCefxoprecltiveedr wIoeihgahvteignremaatleer fatndrefseemravlees mallards was 17.6 ppm. 6G,rwohsislePamtahlollaordgsy:inAtdhueltcomnatlrlolaradnsdi 17t.h6ep1.pmatnrdea6t.m2enptpgmroturpesatvmeerntesswaemrpelesdaactriWfieceedkat20W.eeAlkl mnoatllraerldastewdetr0etsruebatjmeecntte.d (I0ngcriodsesncneecorfospmsayl.lAellstfsindwiansgsnwoteerdedcuornisnigdegrreodsstonebceroipncsiyd,enbtuatlwaansd. considered incidental to treatment "sTuebnjemcatleldar(0d gorfofspsrinnegcr(opaspyp.roxiRmeastuellsy f1r2omwetehkesnoelcdr)oppseyr tsrheoawtemedntthgatrosuepverwaelremaslalmaprdlsedfaonmd cach treatment group had bumble foot. In addition, a single mallard rom the 17.6 ppm {reatment had broken feathers, had an unkemp appearance and retained its yolk sac. For 4 600350 Kmiadlneesy,.onHeowmeavleero,fftshpsreinfgifndrionmgsthweer1e7.c6opnspimdetrreedatinmceindtenltaaclkaenddthuenrpeolsatteeridotroptorretaitomneonft.the lef Histopathology: Various tissue, including the liver, brain, kidney, gonad, proventriculus, gwaelaltbmleandtdse)r,aanddipjousvee,nialned(BalulrstaroeaftFmaebnrtisc)iumsa,llwaerrdse saanmdpleexdamfirnoemdaduunldte(rcoantlrioglhtamnidcr1o7s.c6oppep.m There were no ksions in the liver, kidney, proventriculus, gal bladder, ovary, bran, or Bursa Fabricius in cither adult male and female mallards or offspring at any of the PFOS concentrations tested. There were also no treatment-related lesions in the adipose tissues of madiuclrtovefseimcaullaetsionanidn adouflftipmrailnegs woafs gcrietahteerr isnext.he 17.H6owpepvmert,reattmheent.incIindaedndcietiono,fthadtiepsotsese of adult males exhibited several features including aspermia (complete absenceofmature "sTpheermiantcoizdoean)c,e doefcsrmeaalsledtesstpisersmiazetoagnednetshisraenddulcoerd ddeicarmeeatseerdofstehmeinsiefmeirnoiufserboulsetubduilaemsetweerre mfionrdeinpgrsoanroeunpacretdoifn tmhaelensomfmraolmpthhyesi1o7l.o6gpicpaml tprheeantmoemnetnaosncocmopnsairsetedntowicotnhtrpoolss.t-rWehpiroldeuctthievsee phase regression, the overall findings suggest that testicular regression may have been accelerated in the 17.6 ppm treatment as compared to the controls. However,a definitive statistical analysis of these data to evaluate the significance of these findings could not be dcioentdaurcytL ed duOe twoaAtshdeestEmearlmliCsnaemdploebesiz1e7.(6N=p5p)m. PBFaOse.d on th effects observed in mas, the RPeFpOrSodcuocncteinvteraRteisounletss:teTdhienrtehewesrtuedyn.o Wthriealtemtehnetr-reewlaatseda elfifgehcttsroednucetgigonpirnodeugcgtipornodautctainoyn ipnrodtuhecti6o2n api p1m.8 atnrdeat1m7e.n6t,pptmhisexrceedeudcetidonconwtarosl nleovtelsc.onsWihdeernedcotmrpeaatrmeednttormeallatleadr,dsa5inetgheg control treatment, there were no effects on embryo viability hatchabiliy, hatching heal, and spuerrvihveabnilpirtoydiuncemdallianrtdhsefr1.o8m atnhed P6.F2OSpptmreattrmeeanttsm.entTshwerheenwecroemfpeawreerd 1t4o-dcaonytroollds.surTvhiveosres sriegdnuicftiicoannscewoefrethtehseereesfufletctosfifedwiefrfiecugletsb0eiinmtgesreptretfosrinicnecutbhaetinounmnbetrhoefe1t4r-eadtamyenotlsd.suYrevti,vitnhge. offpring per hen from the 17.6 ppm treatment were similar 0 thatofthe controls. When rceopmrpoadruectdivteoentdhpeoicnotnstrionlthtere17a.6tpmepn,mtrheeraemewenrtethmatinwoerrerneodtucsttiatoinssticianllysesviegrnaiflicnanotm.maTlhiezseed heanidcpholiinntgsslcignecsludesdc,a rneduumcbteiorn ionf thheatncuhmlibnegrshoenfidhaayl,chlianngd3-wnkumcbmebrryoso,f nusmubrveirvinogf offspringcniday. Finally, there were no apparent treament. related cffects on the body rweepirgohdtucotfivheatrcehsiunsg, tohrejduiveetnairlyeNmOalAlEarCdswwahsednetceormmpianerdedotboeco1n7t.r6oplpvma.lues. Based on these Hatchling and Juvenile Mallard Results: jTuhveerneilewe(r1e2 wneoekapopladr)enmtalltarradtsmeinnta-nryeoaftetdheefPfeFcOtsSotnreatthmeentbso.dyWhweeinghctomopfarhaetdchtloicnognstraonlds, Wthheirleewtehreemneoantrleiavtemrewnet-irgehltatoeftdheeffe1c.t8sopnpmjutvreenaitlmeenltivgerrowuepigwhats asttaatinsyticcaolnlcyegnrteraatteirontheasntetdh.at 5 000352 omfecaonntbrooldsy, wtehiegehftfetchtatwawsasnootbsdeorsvee-ddeipnejnudveennitleasndfrmoamythhiasvgerobuep.en aThfeundciteitoanryofNtOheAEgrCeatfeorr hatchingand juveile mallards was 17.6 ppm. "Table 3. Mean liver and body weightsofhatchling andjuvenile mallards rom various PFOS R treatment 5 e eee (ppm) Hatching Juvenile Weight (g) Con1t8rol 22884411240 1100615223912 27206.869+35.0150 62 176 33404 350416 10%:271 1030235 B02 2722549 TATEwep mea ae "AJurvehnili ebodynandlic verweie ghtsnwneTrems easuree EdanpeprooxihmahteelSy o12nweeakms peosntatchp.0.05 Concentrations of PFOS in Blood and Liver: A`Adduullttsmallards accumulated PFOS in a dose-dependent manner (Table 4). To examine the relationship between exposure and tissue concentrations, the estimated average daily take (fAoDmI)caocfhPPFROOSSbytraedautlmtenmtalglraorudps awatsemciormatpiaorne.d and live samples were collected at Week 6 while tFoorlitvhere a1n.d8 asnedru6m.2copnpcmenttrraetaitomnenstcso,lsleecrtuemd for the control and 17.6 ppm ratments, the sWeereukm 6a,ntdhleicveornwceenrtercaotliloencstiendastewreumekan2d0.livTehriisnamnaalllyasirsdwsawsobuladsebdeoanpptrhoeaacshsiunmgpstiioandytisatatbey. AexnpoAsDuIrewtahsatuasdeudltinbitridss amnaalyyseinscboeucnatuesreitnhitshepaernavmiertoenrmeinstc,omTmhoenlreysuultssedoafsthaemreeagsruesrseioonf analysis for PFOS concentrations in both serum and liver and ADI ofPFOS are given below: Male Serum PFOS (ug/ml) = 41.62 (ADI, mg/kg-day) + 0.4595 Liver PFOS (ug/g) = 2.717 (ADI, mg/kg-day) - 0.4814 RI=07177 R=0.6676 Female:Serum PFOS (g/m) = 42.80 (ADI, mgsday) - 12.67 Liver PFOS (u=g3./012g(AD)I,mg day) - 1.124 R=07827 R=0.6048 "Thus, there was a moderate corelaton between increasing dose and serum and liver vel. 6 ROBE "Tabled. Mean concentrationsof PFOS in iverandserum from adult mallards TTreamemt LverConc. Sem Conc." Gm) (ppm) Sex (ug) Weeks Week 20 Control MM 0157:029 <I0Q T39:264 180 MFMo 001823062:00176358 17<2L405Q41 1054165 Eo 023720105 3654371 620 MFo 01615904400462524 314777+2215108 176 MF 9956984852916 3100194260625 11454822677080 CSoarclrindfstWiTec7e6ekpdo Awleasstrrcogpenwessrmaanscandd aandWar de2e0viwikionlson18a we0tW6e7bi.eameswe #100forserum was 0.01 gm Smeexa-ssupreecdifact sdtiufdfyeretnercmeisnawteiroen.obWsietrhviend tfhoersbaomteh tlriveeartmaenndt gsreoruupms,PPFFOOSSccoonncceennttrraattiioonnss aisn cliovnecresntorfatmiaolness inwermeale1.1se1r0u4m twiemrees agprpartoexrimtahtaenlytho1s.e1 itno th5e tviemerss gorfeafteemraltehsa.n PPFFOOSS concentrations observed in th serumoffemales sampled from the same treatment groups. A closer evaluation of the relationship between PFOS exposure and tissue concentrations prreevdeiacltisveex qaunadntittiamteivdeepreelnadteinontshdiipfsferbeentcwese.en Tchoencseentdriaftfieornesnceins emnavkieronitmedinftfailculmtattroicdeesvealnodp itnistshuee ccoonncternotlraatnidons1.7.6Inpppamr,trteiastmveanrtiasbiwleirteyiexdpuocse0d tfhoer e2x0pewreiemkesntwahlidleesimganllwahrdesreinmatlhelar1.d8s and 62 ppm treatment groups were exposed for only 6 weeks. Variability in the PFOS tcohnrcoeungthroauttiotnhedastuadyw.as Falosroidnusetan0cel,eampcoormalpadriifsfoenrenocfesWeinekPF6OSanadccWuemeulkat2i0onsebryubmotdhatsaexfeosr cmoanntnroelr abnudt t1h7a.t6 tpheprme wtreeraetmdeinftfsersehncoews tihnatthPeFpOaSttewmasofacaccucmuumlualatteidoninbaettwiemeendmeapleendaenndt female mallards. In male mallards from the 17.6 ppm treatmen, tere was approximately a 1.6-fold increase in serum PROS concentrations over this time period; however, this difference. was not saisically significant. Over the same time period, female mallards from the 17.6 sptpatmisttirceaaltlymesnitgneixfhiicbanitteidnacnreaapsprionxismeartuem$P-fFoOlSd icnocnrceeansterai tisoenriunmfPeFmaOlSescoinsceinntdriactatiiovnes.ofTthhies presenceof additional processes that differentially regulate the disposition of PFOS in male asnedrufmemtoaloethmearllianrfdosr.matAiocnocmoplalreicsteodndoufritnhegtthempsotruadly tsruegngdesstosftPhaFtOeSggc-olnacyeinntgraitnifoenmsailnesblmoaoyd bdeoasengirmopuoprtoacncturprreodcedsusriinngtthhedifsipsotsi1t0iowneoefksPoFfOtSh.e Fstourdyi,nsdteacnclei,npeedadkureigngg pthreodnuecxt!i6owneienktshi,s and totaly ceased over th last 4 weeks ofthe study. Changes in egg production were related 1P0FcOhSancgoensceinntrsaetriuonmsPiFnOfSemcaolnecsenwuearteiona.pproAxtimWaeteelky63,.3d-utriimnegspleeassk tchgagn ptrhoodsuectoibosnc,rvseedruimn omfalfeesm.alAetmWaleleakrd2s0w,ewrheenonelgyg1.p1rotdiumcetsiosnshatdhacneatsheods,e cmoenacseunrteradtiinonmsaolfes.PFTOhSesien bdaltoaodinsdcicrautme 7 000352 cthoantcenatsraetgiognsptroodluecvetlisonthadtewcereraeseeqduivinalefnetma0lemsa,lethvearleuesw.as an increase in serum PFOS Atosatarkeesulitntooftchoensseisdeersatpieocnifthiedirfelpreoednuccetsivien PcRoOndSiiaocncumouflafteimoanleisn mawlhlearndsi,nietripritmipnogrtatnhte toxicological significance of blood serum or liver PFOS concentrations that may be collected `as apartof environmental monitoring programs. PAconFnaclOeySnstiCrsoantoicfoennst1r2pae-trwiseiocsntks nionljJduuvvejenunivlieelnseislpeostm-ahlaltcrhd (Tsaebrluem5).andHowfievveerr,indtihceatseedrumthaatndPlFiOveSr PorFgOinSalcloyncdeenptorsaittieodnsinion tjhuveeniglgefmraolmlaarndsexrpeopsreesdenftemoanlleymaallfarradc.tionPotoeftnthiael tlootsalesPfFrOoSm tdheeposjiutvieonnilien imaslsluaersdsothirncltuhdaen lsiuvcehr orprosecreas.ses Taos asgsreoswsth.thediqluuatnitoint,atdiveepurrealtaitoinonsahnidp rbeegtrweesesnionjuavneanliylseislivwearsacnodndsuecrtuemd.PFTOhSiscaonnacleynstirsatiinocnlsudaendd aclgethyeoldkatac,onicnecnlturdaitniognsd,ata tcthoranetcaetwnmaternsattagibrooonvusepa.rtehTehelimrietlaotfiodnestheicptbioentw(eLeOnDc)ggbuytollkesasntdhjaunvetnhieleLOsQer,umfraonmd claicvehr PPFFOOSS Liver PROS (ug/g) = 00131 (Fg yolk, g/m)~ 0.0157 Serum PFOS (ug/ml) = 0.0247(Egg yolk, pg/ml) -- 0.2928 R= 08804 R? =09007 "iTnhtuhse,leigvgeryaonlkd. serum concentrations in 12-week old mallards are highly corelted with levels dPeRpOenSdecnotncmeantnrnaetri,onwsitihn tthhee glrievaetreastndcobnlcoenotdrasteirounms oocfcjuurveinnigleinmamlallalradrsdsinfcrroemastehde i1n7a.6dpopsememxaplolsaurrdes.wasTh2e3.1avearnadgeranragteido forfomPF3O.3S2 tc0on3c9.e1n.traTthiiosnsavienrasgeerusmertuomtthoativinrirvateiro bwrasjusvirmiillaer 10 that observed for adult mallards (27 witah range of 2.33 to 50.7) "Table 5. Concentrations of PFOS in liver and serum of 12-week old juvenTirleeamamlelnartds. * Tver Cone. Serum Cone. -- e (p1p3m) "(uLgloeg)u 005(0u7g/0m0l)7--01 16726 0026p2r0e0y168 000479364000.148646 RdTopClccnesnaaliyoensfpSeee dsampmleni,nDiwtihhgSivaennodn 3Gwents. (paMes but L0Q for iverwas 0.01 gig whileserumwas 0.01 gm. C1o7n.6cepnptrmattrieoantsmeonftsPdFuOriSngintheMaflirlstaradndEsggtsh: wEegegks owfergeesapmropdluecdtiofnr.om Etghgescownetrroel,se6p2rsatnodd 8 000351 ifnotroPtFhOreSe c(Toambploene6)n.ts, egg membrane, albumen and yolk, and each component was analyzed "Table6. PFOS concentrations (ug/m)in mallard egg components * Treament `EzzMembrane "Albumen Yok (ppm) Lueck week Iweek 6week Iweek Gwoek TComol 62 <L0Q" 004 <0L0707Q <<LLO0QQ <<LL0OQQ 8<3L40Q <L6O1Q oo) 0018) @m 6m 176 0020620) (00304625 000003) 0000004) (42875) 953077) TCsRaondrnddceviesionns.oOfnGEECompoRetsWer epoin cwerwight bass. Dots peered 5 mars and 2 LOQ isthelimit ofquantiation 001 ig) Fhoern edgiegtsarsyamepxlpeodsuarteboctohncWeneterakti1onasndan6d, aPFpoOsSiticvoencreenltatriaotnisohnisp iwnaesggosb.serFvuerdthbeertmowreee,n tahdeurlet waterceacdhiftfreeraetnmceenstbleetvwele,enwitthheycoolnkcehnatrvaitnigontsheogfrPeaFtOesSt cmoenacseunrteradtiionndsifwfheirelnetaelgbgumceonmphoandentthes laenadst.WeWehken6 PbFyOStrecaotnmceennttraltevieoln,stfhoer ccaocnhcecntgrgatcioomnpsoninenetggwecroemcpoomnpeanrtesdfboertWweeeenkWe6cwkas| generally grater than those measured at Week 1. The exception to this was observed for aFolrbumtehne w6h2erepPpFmOStrceoanmceennttr,atitohnersesliwgahtslyarpepdruocxeidmaatteWleyeka 61w.9h-efnoldcomipnacrreeadsetoiWneePkFO1.S cpopnmcenttrreaattimoennstbheetrweeewnasWeapepkrox1 iamnadte6lyfaor6.6eogglmdeminbcrraeansee ainndmeymolbk.ranHeowcoenvceern,trfaotriotnhsew1h7i.l6e "TTohreyoilmkpltihcaeteiownassoafptphreosxeimoabtseelryvead 1d.i0f4f-efroelndceisncareeasdeififniccuoltnc1e0ntirnatteiroprnest obvuetr sticsetitmoeipnedriicoadt.e heagtg tchoemapdounletnftemPaFleOSmaclolnacrednsthraatdiyoentsnboytatchheieevneddosficWaedeykst1atefowrictihthreerspdeocstetogrsoeurpu.m,Iinsvtreado,r PInFpOaStctonhceeenttrraetnidosnsarienmboostth leigkgemlaeymrbersualnteosftahned fyaoclkthwtertehsialdlulitnfceremaasliensghuapdunotnillyWbeeeekn o6.n the treated dit steady sat. for approximately one week prior (0 cgg production and had not yet reached rAelaftuirotnhsehripevbaleutawteieonn eogfgthyeolgk gPFPOFSOScondcaetnatrsahtoiwonesdatnhdatPtFheOrSe ewxapsosaurreel2atsivmeelyascuornesdtanbty a`wvaesraagpeprdoaxiilmyaitnetlayke15(AfDorD.bothFotrhew6e.e2kan6,d t1h7e.6avpepramgetryeoatlmkenPtsF.OSThciosncaetntorawtaisonsitmoiAlaDrItoratthiaot rsaltoipoeodefrirevgerdesfsrioomn amordegerlewsasisoanpapnraolxysiimsatoefltyhe13y.o1lk PFOS concentrations and ADI where the Yolk (ug/mi) = 13.082 (ADI, mgkg-d+a2.y25)9 R= 08568 Hcoonwceenvterratitohnes wraelsatsiloingshhtilpysmobreetwveareinableex.poFsourreinsatnadncee,gtghmcegmgbmreamnbcraanned:AaDlIburmaetno fPorFtOhSe 62 ppm treatment was 0078 while for the 176 ppm treatment it was 0.095. A ratio 9 60355 ccoonmcpeanrtriastoinonsc.ouldBansoetd be on calculated for albumen due this preliminary analysis, it to the can be lack of quantifiable concluded that yolk PFOS PFOS `concentrationsweretebest indicatorofenvironmental exposure. Smienacseurneod tirneathtimsenstt-urdeyl,atqeudanatditvaetrisvee erfefleacttisonswheirpes boebtsweerevendegfogr caonnycenrterpartoidouncstiavnedpeafrfaecmtesteirn hatchlingsorjuvenile survivaroenrost given in ths report. CONCLUSIONS: M17a.l6epapnmd.feTmhaelecomnatlrloalrdasndwe1r7e.6expppomsetdretaotPmeOntSmaaltldairedtsarwyecroenceexnptorasteidonfsoorf109,we1e8k,s6,.2whainlde the 1 and 6.2 ppm treatments wreament-relaed_mortaliies or were exposed overt signs for of only 6 toxicity wecks were prior to termination. observed at any No PFOS cefofneccetnstroantifoenedtecsotends.umpWthieonn actoemipthaerreWde1e0kth6eocronWteroelktr2e0aotfmtehnte, stthuedrye.weNroetrneoaPtFmOeSn-trreellatteedd e1f7f.e6ctpspwmertereoabtsmeernvtehdaidn rfeedmuacleeds abtoadnyywdeoisgehtesvwalhueantecdoimnptahreesdtutdoy.coAntlroWles.ekIn20a,ddmiatlieons,imnatlhee mtoalcloanrtdrsolisn.theWh1i7l.e6 ptpesmtitcurleaartmreengtrehsasdiaonn iisncarenaosremdailncpihdyesnicoeloofgiscmaalllprtoecsetsess,whtheenbcioolmopgaircaeld tshiegnciofnitcraonlceogfrotuhpecionuclrdeansoetdbiencfiudlelynceevailnutahteed17d.u6eptpomthteresamtamlelntsagmrpolueposviezer. tIhnatadodbisteirovn,edthien significanceofthis finding is difficult (0 interprei that no treatment-relatd effects or male rNeOlaAteEdCeffaencdtsLwOerAeECobsfeorrveaddulotnarnedprjoudvuecntiiloen einndptohiisntsstuedyv.aluatBeadseidn othnetshteusdeyreasrueltsg,ivtehne A(Tdavbelresse7E).ffecTtheLevNeol (ObLsOeArEvaLb)levaAlduevserfsoer PEFfOfeStmeLaevseulre(dNiOnAvEarLi)ousantdissLuoewmeasttriOcbessearrveaabllseo reported (Table5). 10 GhOsR6G "cTharbolneic7.piMleotasstuurdeymewintthemnadlploairndtssaannddtahsesrocoifaftsepdridnigctary NOAEC and LOAEC values for PFOS ina Endpoint * Dictary NOAEC (ppm) Dictary LOAEC (ppm) ADULT Mortality 2176 Body weight Female>s 176 Males = 17.6 Feed consumption Males = 6.2 2176 Liver weight 2176 HiGsrtoospsaptahtohloolgogyy 176 Females > 17.6 Males= 176 Reproductive Mal2e1s7=662 OFFSPRING HKa-tdchalyinsgurjvuivveanbiilleitbyody weight 2S117766 Juvenile iver weight 176 "CAolntconcaenndra1t7i.o6nmsgrePpFoOrSteIdCaEmeawseatswericgbhasbeadsoin.Weck20dts wh 6 pet sls bed om Week LOAEC for molesbas on sitisicllysignificanteduction nbd wight n O6RO3T7 `piTlaobtlest8u.dNy OwiAthELPFaOnSd. LOAEL values in various matrices in adult and offspring mallards ina chronic: Measuresof PFOS Exposure * "ADULT MALES -- NOAEL -- LOAEL -- DAoDsIe((mpgpmP)FO*S/kg body widay) 60.929 31.7660 SLievreurm ((mggmP)FOSkg) 347 Lio 158 96 ADULT FEMALES DAoDsIe((mpgpmk)g body wi. day) 176 360 LSievreurm(a(uggii)ml) 14 97 OFYoFlSkP(RuIgNhG) 507 Liver (e/g) Serum (g/m) 00262 049% Cconotnolcanedn17a.r6etmpgoirPtoRnoOnsSEwertewsesigahtebaeidonWeakFw th 63pp ressa Bd onWeek 6do AT NsoenvLaorsw.effec values or diet and ADI ae basedonconcentration. Scrumand ivereffect values remeasured LOAECfor malesbased on asata significant reduction inbodyweigh. DATA QUALITY: Reliability: Klimish ranking = REFERENCES: GwailtlhagthheerM,alSlIaPr,d.VanWHiolvdenIR,ntLe.maatinodnBale,avLer.s,, P1rBo.jec(t20N0o3.).4P5F4O-S1:05;A3plMotRerpeoprrtodLucatbivReeqsuteusdty No. U2723 Gaanldlagmhaelrl,arSd.P.li(v2e0r01f)orExatnraalcytsiiosnoufspiontgasHsPiLuCm-PEelfelcuorroosopcrtaanyeMsauslsfonSapteectrroommetmrayl.lardCseenrturme `Analyical Laboratories, Inc. Study No. 023-042. Gallagher, `membrane, SP. (2001). albumen, and yoElxktrafcotrioannaloyfsisPoutsaisnsgiuHmPLC_P-eErlfelcutorroooscptranaeys/uMlafsonsatsepecftrroommetryc.gg Centre Analytical Laboratories, Inc. Study No. 023-063, OTHER: Last changed: 05/05/04 2 GenaTs