Document 3J8qvrgE24Za7opvmmepKdGEy

`Summary PFOS Rat Cross-Fostering Study Numbers: 3M T-6295.13, Argus 418-014 Compound & Lot: Analytical Request PFOS (Perfluorooctanesulfonate) 53030) ~Lot 217, 98.4% pure (SMD CAS. Registry Number: 275-393 Study Title: Oral (Gavage) Cross-Fostering Study of PFOS in Rats Report Date: 23 July 1999 (in-life); 11 February 2000 (serum analysis) Study Year and GLP status: 1998 - 2000 and GLP study PPreorcfelduuorreoso:ctaGnreosuuplsfoonfatfeem(aPlFeOrSa)tsb(y2d5a/iglryouopr)alweinrteubaadtmiionnisattedroesdePloetvaelsssioufm0 or 1.6 fmegm/aklge/draayts. wDeorseidnogsestdarftoerd4w2hdeanysthperifoermatolemsatwienrge taoppunrtorxeiamtaetdelmayl7es0.daAyftseorldm.atTinhge, dosing continued in the females throughout gestation and the 21 days of lactation. cArtospsa-rftuorsitteiroinn,g tohfe lciotnetrrsolanadndfotrroebatteadingirnogupphsawrmearceoskuibndeitviicdseadmipnlteos.addFiotriocnraolssg-rfoousptesrifnogr, the litters were transferred to another dam which had delivered raise its own litter. The four subgroups were as follows: contol no dam was allowed to dams with litters from ccoonnttrrooll);dacmosnt(rnoelgdataimvse wcointthrolli)t;erstrferatoemdtdraeamtsedwdiathmsl;ittaenrds,ftrroematterdeadtaemdsdawmitsh(lpiotseirtsivferom control dams. On where possible. day of lactation 4, litters were culled to 10, with equal numbers per sex pOunpslaocftactoinotnrodlayanodnetr(edaatyedolfibtierrtsh)noltunugseadndforlicvreorsssa-fmopslteesriwnge.reTchoelsleecttiesdsufersoammspelleesctweedre fixed for electron microscopic evaluation. In addition to the cross-fostered liters, eight control dams dams and litters were assigned to pharmacokinetic sample and litters collection and two exposed on day 14 of lactation. the dams. SPaumpplseesruomf amnildkl,ivseerrusma,mpllievesrwaenrdemoibltkaisneecdreatnindg pgoloalnedds fwreorme obtained from the litters AcnoarlryetsipcoanldiLnagbo1r0atthoerydafmosr.posAsllibslaemfpulteusrewaenraelyfsrioszen and sent to the 3M Environmental aOnnddlaiytesrso.f lLaictttaetrisoanm2p1leasndwe2r2e, Speoorluemd.nAdlllisvearmpslaemsplweesrweefrreozoebntaainndedshaitptpeerdmtfortohme 3dMa.ms Environmental Laboratory for possible future analysis. CCoo05 tRheesuplrtes-:maMteiangn abnoddygewsetaitgihotnspweeriroedsr.edTuhceesdeinbothdey wweeaitgehdt(e1f.f6ecmtgs/ckogr/rdealya)tefdewmiatlhesredduurciendg sfhooodwncobnysutmhpetfioolnl.owRiengdudcatead. pCuopntsruorlvidvaalmsocXcurCroendtrionltpwuopsofhtahde3f/o1u9r1s(u1b-.g6r%o)uppuspasdeaths d(seiantghlse (ddeeaatthhsininthreoef l1it2telris)t.tersT)r. eaCtoendtrdoalmdsaXmsTrXeaTtreedatpeudppsuhpasdh3a4d/11767/1(1696(.29%.)6%p)uppup deaths deaths (deaths (single in 10 death of in 11 liters). two litters). Treated dams X Control These data indicate that pups had reduced 2/181 (1.1%) pup. pup survival was a result of pup exposure in utero and not a result of effects on the dam from exposure. Electron on Type ImIipcnreousmcoocpyytoefstnheordoayn-othled rat pups' lungs lamellar bodies showed or lung snuorfcacotmanpto.unEdl-eectlraotned changes lmiivcerroosfctohpeypoufpsthefrloimvertrdeiadterdevdeaamlsahcaodmipnocurneadserdelnatuemdbeefrfe(c2t1i0n 3thXe)doafy-poelrdoxriastopmuepss.. The cPoemrpooxuinsdo-mreelpraotleidfleirvaetriocnhiasnageksnoiwn nthPeFnOeSw-bliovrenr erfaftecptupinderaltis.verTehdisfrfoimnddiangmsindtriecaatteeds with PFOS at 1.6 mg/kg/day. O1n4,lycotnhteroalnadlaymsiss(onf=8s)eraunmd stahemiprlleistetrsak(enn=dSu)ridnegmotnhsetsrtautdeydilsocwombpalectkeg.rouOnnd llaecvtealtsioonfday PPFFOOSS,bweiltohwstehveenloowfetrheliemiitghotfpqauiarnst(itdaatmisona(n<d 0l.it0t5erps)pmh)a.vinTgheseeriugmhtchocnocnetnrtorlatpiaoirns(odfam and two litter) measured 0.08 ppm exposed dams had serum for the dam PFOS levels and of 0.1 ppm for the 98 and 218 ppm. pooled pup serum. For the dam with The the 98 pvoplmumvealutoe,dtehteerpmoionleedthpeuspesreurmuPmFwOaSs caton$c9enptpramtiPoFnOSf.romThtheerepuwpassaisnssoucfifaitceidenwtistahmtphlee dam having the 213 ppm serum PFOS PFurposmcsaenroucmcusramapftleersbtiartkhenvioantdhaeymsil2k1. aPnodo2l2edofselracutmatfiorno,mitpuispseviindelnitttetrhsabtoerxnpofsruorme of untreated PFOS on advaemrsagaen(dnc=ro4s)s-cfoosmtpearreeddwitoththterieratterdeadtaedmsfo(sotnelry-deaxmposseerdumvivaalmuielsk,) had 34 which ppm uanvterreaagteedd 7d2ampspm(.onlSyeerxupmosferdominluittteerrso)bhorand 5to4tprepamtedPFdOamSsoannadvcerroasgse-f(onst=er6e)dctoompared dtiogitthepirpumntPrFeaOtSedlfevoesltsero-bdsaemrvseedruinmtPhFesOeSunvtarleueast,edwfhoiscthera-vdearmasgiesdm2o.s5t4 lpipkme.lyTfhreomsingle- peuxppsosfurroemtounctornetaatmeidndaatmedsphuapd usreirnuemaPndFOfeScevsa,lsuiensceataollrubnetlroeawtetdhedlaomwserwhliimciht offostered tqrueaantteidtadtaiomnso(efxp0o.0s5 epdpmin.utLeitrtoerasndfrvoima mtrielakt)edhaddamtshewhhiigchehswtesreercurmosPsF-fOoSstvearleudesto, other waveerreaginintghe8r8apngpemo(fnf=os6t).er-Idnatmhisserlautmtervaclausee,s t(h8e8ppopomleodnliatvteerrsaegreufmorPlFitOeSrscvosn.ce9n8trpaptmions + tohneaevnedraogfethfeorltahcetiartiroenpepcetriivoed f(odsatyesr-2d1amasn)d. 2It2)s,hoaunlddtbhaetnpoutpesd hthaavtetlhiekseelysasmtaprlteesd oarneffereodm around lactation days 14 and 15. Their only exposure would be in utero or via milk from 000G0S treated dams. via milk. These analyses clearly demonstrate that exposure occurs both in utero and C6o2n9c5l.u9s)iwonass:a RreesduultceodfppuuppesxuprvoisvuarleoibnsuetrevreodainndthneotParFeOsSulrtatorfepefrfoedcutcstoionntshteuddaym(sfereoTm- peefxufpleomcstousnrea(.rinycIrsneu-arusftaeecdrtopaenetrxopbxoyisspuourmpeesosdf)oPbeeFsiOnnSogtp(radepaspmeenattrreitnaotteahdfefaentcet1we.-d6bbmogyr/nekxgpp/uodps.auyrT)ehcteaonpPrrFoedsOuuSlcttiiinnoanlrieovrfeor. Pups from can be exposed exposed dams. to significant levels of PFOS from in utero exposure and via milk NOTE: taken for AplostshiobulgehasnaalmypsliessooffPlFivOeSr,, urine, these sfaecmepsl,emsilhka,veanndotmibleke-npraonadluycziendg. glands Two were PadFdOitSiodnuarlipnhgaprrmeagcnoakninceytaincdstlaucdtiaetsiown.ereThuendfeirrsttaksetnudtyoebxeattmeirnechsartahcetdeirsipzoesdiitsipoonsoitfiboondoyf dbiusrpdoesnitaifotnerthprroeuggnhanpcryegannadnctyhraonudghlagcetsattaiotni.on.InT-lhiefesiesccoonmdplsetutdeyoenxathmeisneesstutdhiees; ahdodwietvieonr,, aanmaelcyhsainsiisstinoct/cpohmaprlmeatceo.kiRneeptoirctsstaurdes eixsppelcatnendebdytoAustgaurtstin3t1h,e2s00e0c,ondIhnalf of 2000. The toxicity to objectives of this the pups; 2) more study ase: precisely d1e)fitonebetthteernou-nedfefrescttalnedvetlhefoprosrseidbulceedmevciahbailniitsy:m of eanndh,an3c)eobotuaricnoamdpdliteitoenaulndpehrasrtmaancdoiknigneotfitchedaptoat.enTtihaelsepertihnreaetaaldedfifteicotnsalofsPtuFdOiSes awsiltlhey selate to serum and tissue PFOS concentrations and potential mechanistic endpoints. eoco? Summary PFOS Rat Cross-Fostering Study Numbers: 3M T-6295.13, Argus 418-014 Compound & Lot: `Analytical Request PFOS (Perfluorooctanesulfonate) 53030) -- Lot 217, 98.4% pure (SMD. CLAS. Registry Number: 275-39-3 `Study Title: Oral (Gavage) Cross-Fostering Study of PFOS in Rats Report Date: 23 July 1999 (in-life); 11 February 2000 (serum analysis) Study Year and GLP status: 1998 - 2000 and GLP study PPerrofcleudourroeosc:tGanreosuuplsfoonfatfeem(aPlFeOrSa)tsb(y25d/agilryouopr)alweinrteubaadtmiionnisattedroesdePloetvaelsssioufm0 or 1.6 fmegm/aklge/draayts. wDeorseidnogssetdarftoerd4w2hdeanysthperifoermatloemsatwienrgetoappunrtorxeiamtaetdelmayl7es0.daAyfsteorldm.atiTnhge, dosing continued in the females throughout gestation and the 21 days of lactation. cArtospsa-rftousritteiroinn,gtohfe lciotntetrrsoalnadndfotrroebatteadingirnogupphsawremraecoskuibndeitviicdseadmpinlteos.addFiotriocnraolssg-rfoousptesrifnorg, trahieselitittseros wwnerleittterr.anTsfheerrfeodurtosaunbogtrhoeurpsdawmerwehaischfohlalodwds:elicvoenrterdol--dnaomdsawmitwhalsitatelrlsofwredomto ccoonnttrrooll);dacmosnt(rnoelgdataimvse wciontthrolli)tt;erstrferaotemdtdraeamtsedwdiathmsl;ittaenrds,ftrroematterdeadtaemdsdawimtsh(lpiotstiertsivferom cwohnetrreolpdosasmisb.le.On day of lactation 4, litters were culled to 10, with equal numbers per sex OPunpsloacftcaotniotnrodlayanodnetr(edaatyedolfibtierrtsh)noltunugseadnfdolricvreorsss-afmopslteesriwnge.reTchoelsleecttiesdsufersoammspelleesctweedre fixed for electron microscopic evaluation. dInamadsdiatnidonlitttoertshewecrroessa-sfsoisgtneerdedtolipthearsr,maeicgohktinceotntircolsadmapmlse and liters collection and two exposed on day 14 of lactation. the dams. Samples of Pup serum amnildkl,isveerrusma,mpllievserwaenrdemoibltkaisneecdreatnindgpgoloalnedds were from obtained the litters from cAnoarlryetsipcoanldiLnagbotroatthoerydafmosr.posAslilbslaemfpulteusrewaenraleysfirso.zen and sent to the 3M Environmental aOnnddlaiytesrso.f lLaicttteartisoanm2p1leasndwe2r2,e speoorluemd.anAdlllisvaermpslaemsplweesrweefrreozoebntaainndedshaitptpeerdmftorothmed3aMms Environmental Laboratory for possible future analysis. 0eCo8 . Rtehseuplrtes-:maMteiangn abnoddygewsteaitgihotns pweeriroedsr.edTuhceesdeinbothdeytwreeiatgehdt(e1f.f6ecmtgs/ckogr/rdealya)tefdewmiatlhesredduurciendg sfohoodwncobnsyutmhpetifoonl.lowRiengdudcatead. pCuopntsruorlvidvaalmoscXcurCroendtrionltpwuoposfbtahde3f/o1u9r1s(u1b-.g6r%o)uppuspasdeaths d(seiantghlse(ddeeaatthhsininth8reoefl1it2telrist)e.rs)T.reaCtoendtrdol daaXmsTmrXeaTs treedatpeudppsuhpasdh3a4d/11767/1(6169.( 29%.)6%p)uppup deaths deaths (deaths (single in 10 death of in 11 litters). two litters). TTrehaetseedddaatamsinXdicCaotnetrthoalt pups had reduced 2/181 (1.1%) pup. pup survival was a result ofpup exposure in utero and not a resultofeffects on the dam from exposure. Electron on Type ImTipcnreousmcoocpyytoefstnheordaoyn-tohled rat pups' lungs lamellar bodies showed or lung snuorfcaoctmapnotu,nEdl-ercetlraotned changes lmiivcerroosfctohpeypoufpsthefrloimvertrdeiadterdevdeaamlsahcaodmipnocurneadserdelnatuemdbeefrfe(c2t tion 3thXe)daoyf-poelrdoxriatsopmuepss.. The cPoemrpooxuisnodm-eelpartoleidfelriavteironchiasnageksnoinwnthePFnOewS-bliovrenr erfaftepctupindrealtsi.verTehdisfrfoimnddinagmsindtriecaatteeds with PFOS at 1.6 mg/kg/day. O14n,lcyontthreoalnadlaymssis(onf=3s)eraunmd stahemiprlleistetraske(nn=du)ridnegmotnhsetsrtautdeydilsocwombpalectkeg.rouOnnd llaecvtealtsioonfday PPFFOOSS,bweiltohwstehveenloowfetrheliemiigthotfpqauiarnst(itdaatmisona(n<d 0l.i0te5rsp)pmh)a.vinTgheseeriugmhtchocnocnetnrtorlatpiaoinrs(odfam and two liter) measured 0.08 ppm exposed dams had serum for the dam PFOS levels and 0.1 ppm for the of 98 and 218 ppm. pooled pup serum. For the dam with The the 98 vpoplmumvealutoe,dethteerpmoionleedthpeuspesreurmuPmFwOaSs caton8c9enptpramtiPonOSfr.omTthheerepuwpassasinssoucfifaitceidenwtistahmtphlee dam having the 213 ppm serum PFOS. PFurposmcsaenroucmeusramapflteersbtiartkhenvioantdhaeymsil2k1. aPnodo2l2edofselracutmatfiorno,mitpuispseviindelnitttetrhsatboerxnpofsruorme of PunFtOreSatoend advaemrsagaend(nc=ro4s)s-cfoomstpearreeddwittohthterieratterdeadtaedmsfo(sotnelry-deaxmposseerdumvivaalmuielsk,)whhaidc3h4 ppm uanvterreaagteedd 7d2ampspm(.onlSyeerxupmosferdominliuttteerrso)bohrand t5o4tprepamtedPFdOamSsoannadvcerroasgse-f(onst=er6e)dctoompared dtiogitthepirpumntPrFeaOtSedlfevoesltsero-bdsaemrvseedruinm tPhFesOeSunvtarleueast,edwfhoiscthera-vdearmasgeisdm2o.s5t lpipkme.lyTfhreomsingle- Peuxppsosfurroemtounctornetaatmedindaatmedsphuapd sureirnuemaPndFOfeScevsa,lsuiensceataollrubnetlroeawttehdedlaomwserwhliimciht ofofstered. tqrueaantteidtadtaiomnso(fe0x.p0o5sepdpmin.utLeitrtoerasndfrvoima tmrielakt)edhaddamtshewhhiigchehswtesreercurmosPsF-fOoSstvearleudest,o other waeverreaignintghe8r8apngpemo(fnf=os6t)e.rI-ndtahmisselrautmtervaclausee,s t(h8e8 ppopomleodnliatvteerrsaegreufmorPlFcOteSrscvosn.ce9n8trpaptmions on average for their repective foster-dams). It should be noted that these samples are from + athreouennddolfatcthaetiolnacdtaaytison14pearnidod15(.daTyhse2i1r oannldy2e2x),poasnudrethwatoupludpsbehaivneultiekreolyorstvairatemdiolkn ffreeodm 0009 . tvrieaamtieldkd.ams. These analyses clearly demonstrate that exposure occurs both in utero and eC6x2op9no5cs.lu9ur)sei.woanssI:na-urRteeesrduoultcexeopdfoppsuuuppreesxuoprfvoPisvuFarOleSoibn(sdueatremvretodraeianntdetdhneoattPaF1.Or6eSsmugrl/attkogrf/edpefarfoyed)cutccsatoninotrnehsseutldutdayimn(lsfievreero.TmepPfuufplesmctocsnaa(nrinybcerseeuarxfspaeocdstepanedtrtoboxyisispgounmpiesfsidc)aobnetesilnneogvteplarspeospefenaPtrFitOnoStahfeffrenocetmewdi-nbbuyotmeerxpopuoepsx.uproTeshuteroepPraFondOduScvtiiiaroumntieolrfko. from exposed dams. taNdaOdkieTtnEiof:noarlAploptshshaiorbmulagechoasknaailmnyepstliiescsoosfftuPdlFiivOeesSr,,wuetrrhieenseue,nsfdeaecmreptsla,ekmseinlhkat,ovebaenntdoetmribclehkea-nrpaarcnotadeluryiczzieend,gdigslTpaownsodistiwoere bPuFrOdSendaufrtierngpprreeggnnaannccyyaannddtlharcotuatgihong.estTahtieonf.irstThsteusdeyceoxnadmsitnuedsytehxeadmiisnpeossittiheon of bondoyf dhioswpeovseirt,ioanntalhyrsoiusghispnroetgncoamnpclyetaen.d lRaecptaotritosn.arIen-elxipfeecitsecdombpylAeutgeuosnt t3h1e,se20s0t0u.dieIsn; ta2od0xd0ii0ct.iitoTynh,te0a otmbhejecephcuatpnisvi;esst2io)cfm/tohprihseasrptmruaedccyoiskaeirles:yetdi1e)cfitosntebuedtthyteeirsnoup-nledafenfrenscettdalnteodvestlthaerftoproisnrsetidhbuelceseedmceovcinahdbaihnlaiiltsyf;mofof eanndh,an3c)eobotuaricnoamdpdlietitoenaulndpehrasrtmaancdoiknignoeftitchedaptoat.enTtihaelsepertihnreaetaaldedfifteicotnsalofsPtuFdOieSs awsiltlhey relate to serum and tissue PFOS concentrations and potential mechanistic endpoints. ccee10 . Aber Of ve fuga on day 11 Conley) postpartun/mmber of Hive Fuga oh Gur + (pestculting) postpartum. S_ B= 8 ; Dee SMINInn mn Iooomomnoomn ome i g . Euciuaes Valve fue iteer 137: he dim vhs fous Sen om day 10 of Lactation: eight ups vere sncrticd g Id 2gS _ 4FE EELS RE RU IERnEaEEtrSaTtmIect 1=c Bao in ep erCosii 3: 7a kv ?