Document peb5vb5MEOmrgNpNNOXpBBRXX

.R an = am - Ssimsn10ssa tom : 08 September5, 2001 AR 226 - 103] (RR 51630 Docume ProcessingCenter 1407) Officeof Toxic Substances U.S. 401 MESntvriereotn,meSnWtal Protection Agency `Washington, DC 20460 Attn: TSCA Section 8(e) Coordinator DELO-BO-37 %| oor v B227 R Dear Section 8(e) Docket Coordinator: Re: `SCA 8(e) Supplemental Notice on Sulfonate-based Fluorochemicals With this letter, 3M is providing final reports and other supplemental information related to previous TSCA Section 8(e) notifications. Manyofthe enclosed items are analytical reports providing blood serum and liver levelsoftest materials forwhichthe in-life report referring to administered doses has already been submitted to the 8(e) docket. In other cases where the 8(e) notification consistedofpreliminary data, we are `submitting a final study report. Allof the enclosed items are already in EPA's possession and available in TSCA Docket AR-226. We believe, however, that placing these items inthe 8(e) docket may allow for more convenient access to information directly related to previous 8(e) notifications by 3M. The table below lists the encloseditemsand references the study or data whichalready has been the subject ofan 8(e) notification by 3M: Related Study/DataAlready | Aamenu ded AnnalyttiAcvaalcShiunedTdy,oSuAb0Gm-einEsetsrhiaytopinoenrlRuaotrRoeoprcoadnuection,|| CDoevmeblionpemdenOtraall a(nGdaPveargien)atealrPloyst,natal Determinationofthe Presence and Concentrationof PFOS, | Reproduction Toxicity Study of N- NMC5er5sl6e:o,,CDnPPBeFEROONVSSaAAAFAAT/,,6P3laP1unR6sdRO.aPStFsAaOnnSEadxAipioiEnscIeatFdhOetRSLoeEipE.voeFGrrOHtaSTniEndOt-hPXOeFH0SO1,eS3,r3.Mof | [63E1t6F.O5,SEJuinneRa3t0s,, 319M99R,efflelrreenpcoerNto. T|| ssuubpmpiltetmeedntFeabrluaeryl1n5,g2000 to | ERNU3093, lune 1, 2001 23 . Coonnttaaiin NO cg =x 85%3 > 2 - I . TSCA Section 8(c) Docket Coordinator . Page? --_--m AttAatacchedhed SuSbubmmiissssiioon RelateFdilSetduUdnydDearta8(A)lready | | Enemtma , | 2. PAnraelsyetniccealanLdabCoornacteonrtyraRteipoonrto,fDPeottearsmsiinuamtionofthe || CDoevmeblionpemdenOtraall a(nGdavPaegrei)natFaerlt/iPloisyt.ratal PSeerrfulmuoarnoodcLtianveesruolffoSnparteag(uCeA-SDaNwulmebyer:Rat2s75E9x-p3o9-s3e)d i0n the || iRnepRratosd,ucAtrigounsTRoexisceiatrychStLuadbyoroatfoPriFeOsS, PFOS via Gavage, Laboratory Report No. U2006, | Inc.. Sponsor's Study No. 6295.9. June February 15, 2000 supplementing. 3. RDeepvoerltopAmmeenntdalmeanntd P1e,rCionamtbail/nPeosdtnOartaall(RGeapvraogdeu)ctFieortniliy, | earlier fling TLoaxbiocraittoyrSietsu,dyInoc.f,PPFroOtSocionlR4a1t8s.,0A0r8g,uSspRonessoera'rschStudy No. 6295.9, April 13, 2000. 4. ACnoanlcyetnitcraaltiRoenpoorftP,erDfeltueorrmoioncattainoensuolftfohneatPer,esence and PLievrefrluaonrdooScetraancSsaumlpfloensy,la3miMdeE,nvMi5r6on,meanntdalMSLa7b0orianttohrey Ref. No. U2636, TOX-028, February 23, 2001 P1e3r-fWleueorkoDoicettaanreysuSltfuodnyamoifdNo-EMtehtahnyo!l || 6(3N1-4M.1e,FOCoSvEa)ncineRSattus,dy3NMo.Re6f3.2N9-o2.2T5-, dJautlyed2J4u,n2e00300, 2000, Section 8(e) filing 5. ACnoanlcyetnitcraaltiLoanboorfaPtoFrOyS,RePpoFrOtS,AD,etPerFmOiSnAatAi,onaonfdtEhFeOSE`OH in the Sera and Liverof CrlCDBR VAF/Plus Rats | | FDienvaellRoeppmoerntt,aOlrTaolx(iGcaitvyagSet)udyof 20NEthylperfluorooctanesulfonamido)- ERRexefpp.oorNstoe.dNotT,o-6TN3O-1XE6-G.07F,9O8SF,Eeb,Lra3ubaMorryEant6,voir2ry0o0Rn1em.qeunetsatlNLoa.boUr2a4t0o2r,y 3M || e6tot3h1Sa6en.co7tl,ioiDnneR8ca(etems),bdeo3rMck1e7Rt,efp1ee9rr9e8ln,ectsteeurNboomi.ftTt-ed August 21, 2000 6. APPnerarelfsyletunioccreaolaocnLtdaabnCoeorsnauctleofnortnyraaRtteeipo(onPrFotOfoSPn)otthoaresasDnieouttmehremrinmaettiaobnoloifttehoef -|| FDEieXnvFaelOlSRoeEppmoiernnttR,aaOblbriaTtolsx,(iSc3itMtoymaRSectfhuedTryeuonbfcee)NN-o. 2E(tNF-OtShyEl)peinrfLliuvoerrooacntdaSneesruulmfoSnpaemciidmoe)n-sc,th3aMnol (N- tTo-6S3e1c6t.i8o,nJ8a(ne)uadroyck1e1t, p1e9r99l,etsteurbmoiftted ELanbvoirraotnomreyntRaelquLeasbtorNaot.orUy2R4e5p2o,r3t MNoR.efT.ONXo-.09T-76,316.3, August 21,2000 February 8, 2001 7. FEimnpalloRyeepodratt,tAhlee3xaMndDeerc,atB.urMFoarcialliityt,yUSntiuvdeiressitoyfoWforkers | 8P(ree)lidmoicnkaerty diantlaetstuebromfitDteecdetmobSeecrti1o5,n Minnesota, April 26, 2001. 2000 s 2 TPaSgCeA Section 8() Dacket Coordinator hed Sabo Related Study/Data Already Attached Subission Filed Under8() { 5. | FFuibinoatrlsfRteogproir,st,, AnAccu,ctePerOrorjalelctTToNoxoiici0ttBy8SS2cvAreeRen0n3ww6ii3thh3TTMO-N3RG2ef9e0rCeonCce||| AAEcvcualteueatOOiroanlnTaolbxiocyirtytSS.ecmreeRniekvnewiriathTT-- ||| Nnod. T4039290H0(,40L96%7K8',PFF-O6S8A75A,iLno3t%SOIE),IONHo,ve1m7b%erP5A. 1582 (Bibliography eniry in Docket AR-326, final report || L0a8b8o2raAtRoDr3ie6s2,,I3nM. RPerofjeercetnNceoNo. T| 3290 (40% K'PFOSAA in' % EOH, was to be moved 10 TSCA 8e) docket] 618773%,[LPoAt aSOnId),4N0o%v0em,bLe57r.7189,82F.- S`Auubgmuistte2d1,to20S0ec0tsieolnf-(a6u)didtolcekeert in (awthhiechtheamnonaeto)usly refers to rabbits 9. GPieersfyu,orJo.Po.etaannedsKu.lfKoannantaena,nAdcRceulmautleadtFilounoroofchemicals in | 8Pr)elidmoicnkaertyMdaaya 2s6u,bm1i9t9e9d to Section | Fh Tissue, Michigan Sate University, June 20, 2001. 10. GPMeiirenfskuyoa1,rn.od2o,cRatinavdneersKOl.tftKeoransna,ntaMenia,cnhdAicgRcaeunlmauSttleaadtteFilUounnoivroeofrsshietmyi,cJaulsnein20, 2001. 11. GRFierelosamyt,etd.h.eF,iGiaonrudoosfhKMe.lmeKixacifnaclnosania,nnOPdyesCfthleeurso,arCporeoacastksaeonsBetasryue,faoMVniiarctgheiingaiancand, State University June 20,2001. 12. GRieelsayt,edJ.FP.luaonrdocKh.emKiacnanlasn,nFPiesrhlEuaotrionogctWaanteesuBlifdosn,aanted Michigan Ste University, June 20, 2001. 13. GPMieaerrsfiyin,oerJMo.oatmaamnnadelsKsu.,lfKMoainncanhtaieng,aannAdcScRaeutlmeautlUeandtiivFoelrnusooirfyo,chJeumnieca2l0s, in 2001. 1 you have any questions about this submission, please contact me at (651)737-4795. Sincerely, N9/ /- GMeaorniaghger,A3dMamCosrporate Product Responsibility Enclosures So . OPPRrIMEDICA ~~ I) 20 tie 5QO Amare '905 Sheehy Drive, Building A 5\6 EisBali Teleophaon.e: ((221185)) 444453..86791807 ee ny `REP1O3RTAAPRMIELN2D0M0E0NT 1 ' PROTOCOL 418-008 SPONSOR'S STUDY NUMBER: 6295.9 & COMBINED ORAL (GAVAGE) FERTILITY, DEVELOPMENTAL AND = PERINATAL/POSTNATAL REPRODUCTION TOXICITY STUDY OF PFOS IN RATS & FINAL REPORT ]1. Page 19, paragraph 4 has been revised to: = Pregnancy occurred in22 (95.6%), 21 (84.0%) and 24 (96.0)ofthe 23,25 and 25 female rraetsspeacstsiivgenlye.d tAolclophraebigtnaatnitodnaimnsthdeel0iv(eVerheidclliet)e,rs0..1Tahnedg0e.s4tamtgi/okngi/nddaeyx dwoassagceomgpraoruapbsl,e S(eFr2opssuptsh)e tthorweeeadnoisnaggewgerroeupasl.soViuanbaiflfietyctaenddbgyrtohwethhoigfhetshtedsoescaognedtgeesnteedr,a0t.i4onmgo/fkfgs/pdrianyg. There were no toxicologically important differencesfrom the control group values. No ctlhienitceaslt aorrtincelceraosphsiygohbsaser0v.a4timogn/skgin/dtahye.F2 generation pups were. attributable to dosages of 2. Page I-10, paragraph 4 has been revised to: TTihfeeeFt1s ognenmeartaitnigonorrefperroldiutcytiovcecuNrOreEdL.iTshgereNaOteErLthfaonravidaobsialigteyoafnd0.g4rmogw/tkhgi/ndahye: F102 generation offspring is also 0.4 mg/kg/day. There were no toxicologically important effects on pup survival or growth at the highest dosage tested, 0.4 mg/kg/day. 3. Page V-8, paragraph 3hasbeen revised to: The viabilityofthe second generation offspring (F2pups) was unaffected atthe highest donisagettheestmedu,m0b.e4rmogf/kpgu/pdadye.at`hSsmaalflteirnDcrLea2seisn itnheth0e.4numgm/bkegr/odfadyadmossagwietghrsotuipllbwoerrnepnuopts {tohxeiccoolnotgrioclagllryouipmpvoarltuaenst; b2e)ctahuesae:ver1a)gtehefovralliuveesliwtetreresniozetssdieglniivfeicraendtalynddisfufrerveinvtifngrotom DviLabi2l1itwyeorrelgarcetaattieorntihnadnicoers fcoormptahrea0b.l4emtgo/tkhge/dcaoyntdrooslaggreogurpovuaplureesm;aarnkdab3l)yndeiiftfheerretdhe from the control group values. Aidan LENp-30-37 0008118278 v \ FINAL REPORT AMENDM41E8N.T008| PAGE? 4. V-8, paragrap4h has been revised to: Phiugphebsotddyowseaiggehttesostfedt,h0e.8semcgo/nkdg/gdeanye.raStmiaonllofrfesdpurcitnigon(sF2inppupusp)bwoedryewueniagfhftescitnedthaet t0.h1e `asnmial0l.d4ifmfge/rkegn/cdesaybedtowseaegne tghreopupusp wbeordey nwoetigthoxtiscfoolrogtihcealcloyntirmoploratnadnt0.b1ecn.agu/skeg:/d1a)ythe ldiotseargseizgersooufptshewe0r.e1 nmogt/kstgaltidsatyicdalolsyasgiegngirfoiucpanotnanDdLswe1retharsosuogciha4t,edaswictohmtphaerleadrgweirthlitvhee c`oDnLt4r;ol2)grtoheupsmvaallluerse,duacntdiotnhse irnapnudpombosdelyecwteiiognhotfspiunptshfeo0r.4comngt/ikngu/eddayobdsoesravgateigornosuopn p`rweerceulalsisnogc,iaatsecdowmiptahraedmiwniitmhatlhley cloanrtgreorllgivreoluiptevralsuiezes,atanbidrtthhe(rDaLn1d)oamnsdeloenctDiLon4of ``paunpdspf<o0r.0c1o,ntriesnpueecdtiovbesleyr)vparteisoenntononDDLL4s; t7haensdtat1i4s,tiacsalcloymspiganriefdictaontthreedcuocnttiroonlsg(rpo<uDp.05 Values, were transient and disappeared by DL 21. 5. Page V-9: Revisions to paragraph 4 on page V-8 caused it to extend onto page V-9. These revisions were NOEL forthe second mgaendeerattoicolnaroifffysptrhienignt(eFr2prgeetnaetriaotnioofn)t.he observations reported and the pis LED Ioier ond G. York, PiyD., DABT ~~ Date `Associate Director of Research `and Study Director Yona] Doge L. ap 7 NancyJ. Gongliewski Date Quality Assurance Manager s : 41R8E-V0I0S8EPDAPGEAG|-E9 {eed consumption values were reduced during lactation in the 0.4 mg/kg/day dosage group. dDaoysaogfevsagoifnatlhepatetsetnacrytiicnlethaesFh1igghenaesr0a.t4iomnglfkegma/ldeayradtisd. nTohtearfefewctertheenaoverage elbiovonalglo-ugtaiectraelmdlyrbeyitmeppneotrritfoanoonrtmadrniefcsfeeprionennsaceepsainsihnsiibtvihteeioavnavloinuiedtsahenfcoFer1loergaewmnaietnrega,rtimsoahnzorfete-pmtaeelrrefmorrraemttsae,nntcaieson, paradigm. Dosages of the test article as high as 0.4 mg/kg/day did not affect any mating and fertility parameters evaluated in the F1 generation female rats. All necropsy observations in the F1 generation female rats were considered unrelated to the test article. Pregnancy occurred in 22 (95.6%), 21 (84.0%) and 24 (96.0) of the 23, 25 and 2id5osofaegmweaalgserorcuaoptmssp,aasrresasibpglenceetdiavcteroloycs.oshAatlbhliepttarhterigeonenandintotsdhaaegme0sg(dVreeohfuiipcvsle.er)e,dVi0la.ib1tielratsny.daT0nh.de4gmgrgeos/wtktaght/idoofany ihe the second highest generation offspring (F2 pups) dosage tested, 0.4 mg/kg/day. to weaning were also unaffected There were no toxicologically by oibmupaorrtvaanttiodnisffienrtehneceFs2fgreonmetrhaeticoonntpruolpsgrwoeurpevaatltureisb.utaNbolectloindicoaslaogrenseocfrotphesytest article as high as 0.4 mg/kg/day 6 .. 418R-E0V0I8S:EPADGPEA1G11E0 Cc. Conclusions OOPEnatrrheeadbboalssai-asegfeoffsectcthaleuosvseeeldda(trNaeO,dEutcLht)eioFonfosPgiFennObeoSrdaiytsiwo0e.n1imgmhagtt/egkmagia/nldaaanyndd(0rp.e4adtmuegcmekadgl/fndeoae-dy and consumption vaiues). TnheeFFaotgseneerrattiyonorreepsrtordouuctsicvyec lNiOngEoLcci urgrreeda.teTrhteh aNnO3E.L2 fmogrkvga/bdialyt;y annodefgfreocwttsh ManheerFd1osgeangeersatciaounsoefdfspprreiinmgpilsan0t.a4tmiognkglo/sdsaayn(d1.r6edmugc/tkigo/ndsaiy iantdr size, pup viability, growth and survival). The (0.4 mF1glgkegn/edraaytidoonsmaagteecmaaulseadndrepdautcetmiaonlsNiOn EboLdoyfwPeiFgOhSt is 0.1 mg/kg/day gain and reduced feed consumption values). T0.h4emFg1/kgge/ndearya;tinoonerfefpercotdsuocntimvaetNinOgEoLrifsergtrietayteorcctuhrarneda.dTohsaegNeOoEf L for viabilty taonxdicgorloogwitchalilnytihmepoFr2tagnetneerffaetcitosnoonffpspurpinsgurivsiavlasloof0.g4romgw/tkhga/tdathye. hTihgheersetwdeorseagneo tested, 0.4 mg/kg/day. ld J sd EMixledcryetdivSe. DCihrreicsttoirano,fPRhe.sD.e,arFcehllow, ATS Date Lon IDolo M. floberman, Ph.D., DABT sie Date Director'af Research (xf itm ie Nn 32 ARsasyoqvpioantde GD.irYeocrtokr, o7f 5.B5pdeAaBrcTh and Study DDiarteector 7 ;. 418R-E0V0I8S:EPDAGPEAVG-E8 B.S. Necropsy Observations(Summary-TableE18;Individual Data- Table E34) AGflohlnrtnerleoacltregodrposouypt;ohbaesnetdrevs2ta)tairttohinecsloeibnbseetrchvaeauFts1ieo:gnecn1)eormtahmteoinoonlbsyfeeromvcaacltueirosrnaistnsotcwhciesurrsertercadoinnisnoifrdaertarste.idn the aThleoste oinbstehrevkaitdinoenys ainndc/luodreudrirnoaurgyhbalnadd/doerr poiftttewdoccoorntterxolofgrthoeupkirdatnse.ysOwnitehof tahlelsse orfattshealusroinhaardy dam baltaaddnegrr.a that died nNuelcarrompastyeroibasleirnvtahteiornesnaflorctohrete0x.4anmdg/tkhgi/cdkeanyed as the result of an intubation error weredescribed dosage group previously. Bs. Natural Delivery and Litter Observations (Summaries - Tables E19 `and E20; Individual Data - Tables E35 through E38) PG5r6oesgtanagameanlcgeryoruoapctssc,uarsrresesidpgenicnetdi2v2teol(yc9.o5h.Aa6lb%li)pt,arte2i1gonna(n8int4.td0ha%e)m0sa(ndVdeelh2iic4vleer()e9,d6.0l.0f1t%e)rasno.fdtT0hh.ee42mg3ge,s/2tka5gt/iadonandy aincdreoxss(tthheeptehrrceeendtoasgeagoef gprroeugpnsa.nt rats with live offspring) was comparable ehTihngehevtsiiatbiidbloiotsymaogpfeutpthseesatseneddc,ogi0nnr.dot4uhgmepegnnwkeuegrrm/aedbtiaenoyron.tooftfoSfpxmsuiapcplroilldnogeigani(ctcFahr2leslapyasufeiptsmsepr)ionDrwttLaahsne2tnuibnnueamtfchbfaeeeucrsteoe:fd da1ta)tmhtshee IV0.av4leurmeagsg/ekwgef/rordealnyiovetdolsisitgaenrgiesfiiczaenstldyedliifvfeerreedntafnrdomsutrhveivcionngttroolDgLro2u1pwvearleuegsr;ea2)tetrhethan or comparable to indices for the the 0.4 control group values; and mg/kg/day dosage group 3) neither the viability orlactation remarkably differed from thecontrol group values. aPtutphebohdiyghweesitgdhotssaogfethteessteedc,on0.d4gmegn/ekrga/tdioany.ofSfsmparlilngre(dFu2ctpiuopnss) iwnepruepubnaofdfyected weights in the 0.1 and 0.4 mg/kg/day dosage groups were nottoxicologically small differences between the pup body weights for tGaihmrnepodoucrwpotneaotrnrnetolDbaLsaesscn1oadcuit0sa.het1r:eomdu1ggw)/hiktt4ghh,e/tdahaseycldoaormgspeaargrleeivdgerwloiituttheprstshwieezercsoenotnfroottlhsegtar0t.oi1ustpmicgva/allklyuge/ssid,ganyainfdidocastnhatege Treadnudcotimonseslienctpiuopn `asociated with a bomfoindpiyumpawslelifygorhltacsrognietnritinhvueee0dl.io4ttbemsrgesr/ivkzaegt/aidtoanbysirdtoohns(aDDgLLe41;g)r2ao)nudtphoewnesrmDeaLll4 red with the control group values, and the random selection preculling, as compa of pups for continued observation on DL 4; the statistically significant reductions 2 / / / o 418-008:PAGE V-9 REVISED PAGE c(opn<t0r.o0l5garnoduppsv0al.u0e1s,, rweespreecttirvaenlsyi)enptreasnedntdiosnapDpLesar7edanbdy 14, DL as compared 21. to the `Aaddmvienrissetlryataifofenctofatnhyeottehsetrarptairclaemaettedroseavgaleusataesdhaitghnaatsur0a.l4dmegli/vkegr/ydoarydduirdinngotthe 21-day lactation period litter sizes, numbers of (duration of gestation, averages dams with al pups dying during for implantations lactation, viability and and live lactation indices, surviving pups per litter and pup sex ratios). B.10. Clinical Observations from Birth to Day 21 Postpartum and NInedcirviodpusayl ODbastear-vTaatbiloenss E(3S9umamnadriEe4s0)- Tables E21 and E22; No clinical or necropsy observations were attributable fo dosages of the test article as high as 0.4 mg/kg/day because: 1) the incidences were not dosagedcleipniecnadleonbts;eravnadt/ioorn2s)itnhceluodbesderovnaeticoonntorcoclugrrroeudpinpuonpltyhoatnewaosr tnwoto npeusptsi.ngTohrese neuarcshinogf,thhaedcodnetcrroleaasnedd0m.o4tmogr/akcgt/ivdiatyyadnodsawgaesgcrooludptsotthhaet thoaudcha, moinsesipnugptiipn of tail and one 0.4 mg/kg/day dosage group pup that had an umbilical hemia. No milk in stomach occurred in 2, 4 and 4 pups that were found dead in the three respective dosage groups. One control group pup had hydrocephaly and one 0.1 mg/kg/day dosage group pup hada raised tan area on the median and left lateral lobes of the liver at necropsy on DL 21. 9