Document aD1beQ0YMgq8VxxJQg7N0vMre
3M MEDICAPLroDtoEcPolAfRoTr MStEuNdTy,NoC.OTR-7P1O32R.2A;TSET-T3O9XICOLOGY
PHARMSTA UDYC OFPO ERFK LUOI ROOCNTANE ESUT LFOI NAMC IDE
INRATS
TSchlpereaarogabunjeceecDtaainvwedloebfiyotrlhaoitgssisctaaufldtpyeearrisssitiosntageslnesceeoosrasflPtdehoerspfeol.tueoAnrntoailoayclstfiaosnorefoStauhlleafbossneoarrmupimtd,ieov(neP,ruF,rOuirSniaArn)yeaainnnmddafrfosoceasl PmfeoFrtOhpoSodtAesn.itsiPatrlheemveiutolautbisomslatitutedeimseesotoafbfPotFlhiOetSeNA-inetwahitylsllb(de1e,rp2i)ev;rafhtoiovrwemeoevfdebrP,yFLtOhCeSMAanSahlayavtniecdaclpoetnrechclahupiosqdoutdehheeurtsed in PptehFreOfsleSsutAourdotiooecrstwaenaesssultuofhnoialnbalitvesetse(ouePdFeaOtnSed)cs.teaaNlrlocphpofthoearnrtmioaatclhoemkreitpnaoebstosiilcbiltseteu,mdeiitenascblohuladivitenegsyeitnbteheenurdionneesocna lafeenvcdeelst.(s3R)pe.octeOennntteliyag,loavmlaeltoiafdbtaothleiidtsesm,etPtuFhdOoSdyss,thoiandvseeteerbruemmeinandnedtehlveivpeoetldenooftowipranltethfodoe,thqieufaloncotciwutraprtaiirontngpo,rfthPbeFieOxltSleAnt of cPchohanarvraemcrtaescrioiokzniaontiefotniP.cFsoOfSANEtoFPOFSOSE. anTdhiistsimneftoarbmoaltiitoenswainld hperlopvitdoeedxapltaaifnotrhperoper risk
Research Client:
33MM CSepnetceiral,tByuCihledimnigca2l3s6Division Saint Paul, MN 55144
Sponsor: Study Location:
3M Specialty Chemicals Division 3SaMintCePnatuelr,,MBuNil5d5in1g44236 33MM CSetnrtaetre,giBcuTiolxdiicnogl2o7g0y-L3a5b-o0r6artooroym SB314 Saint Paul, MN 55144
Study Director:
TAonxdirceolwoMg.y SSpeeacciaati,sPth.D, 33MM CMeendtiecra,lBDueipltd.in/gC2o2r0p.o2rEa.t0e2Toxicology
Saint Paul, MN 55144
Ph.: 651-575-3161 FAX: 651-733-1773
Study Taxicologist: DAdevaannncaeLdueRbekseera,rcMhSToxicologist
L
S33aMMintCMeePndatuielcr,a,lMBDuNeiplt5d.5in1/g4C24o2r0p.o2rEat-e0T2oxicology
000153
:'
Ph: 651-737-1374 FAX:651-733-1773
T713P2F.2O;SSATP-3K9
Proposed Study Timeline
In-Life Start Date: October 4th, 1999
AInna-lLyitfiecEalndCoDmaptlee:tNioovneDmabteer: 2TnBd,A1999
Final Report Completion Date: TBA
R"TehgiuslsattuodryywiClolmbpelipaernfcoer:med in the 3M Strategic Toxicology Laboratory undear defined TprooxtioccoollogayndLaclbasGsiLfPiedPraosgar"aCmlParoscBsedSutrued.y" as explained in TOX SOP 0950, Strategic
Test Material:
Dan Hakes,
PFOSA.
ProductResponsibilityLiaison
'
3M
Chemicals
Division,
villfurnish
high-purity
IdentifiNcaamtieo:n: Perfluorooctanesulfonamide LMootleNcuumlbaerrF:orLm-u1l0a0:0C9,(FPyre;pSaOrNedH,byGeorge Moore, 3M SMD Lab, Bldg 9P29u3r6%i,tpAyup:rrieAlna(41l)9y.s9Qi6us)abliytGatCivMeaSnddeqtuearnmtiitnaetdivtheactotmhpeossittariionngalmraetseruilatlstwhaastwoeverre crdheeavrieinav)le,ed1df8tr.ho7amt%ttChhFee3cs(ioCnmFgpl2oe)stxirti-aiCloFn'(HwCFa/3sF)6--5N(.CM8FR%2)CcyrFo-3sSs(0-Ci2Fn-t2Ne)Hgxr2a-t(SiI0onnt2e-arnNnaaHll2ysi(sNormal bmroannochm)e,th3y.l5%brCanxcFh2),x+111-.2C%F((CCFF33))-2SC0F2~-(NCHF22)(xA-lSp0ha2-bNraHn2ch()Isaonpdro0py.l28%
o(CfEt}hCe-P(FCFO2S)A-sSaOmxp-lNeHre;ve(atl-eBdut9y,l6b0r0anpcpk)m(os)f.PHFPOLS,C/1M,1S00chpapramctoefrization c2Coi4nF,c10e5n0St0Orpa0t:piNmoHon:sf,o5Cf11s04evpFepsrmsalHoSoftOCh;eNFrHa,smiS1dO,e2:0sN0.HBpa,psm6eo,df6oC0n0otFphspemHso;ufSmOCo:yfNFt,HhH;eiSmaOpn:udNrilHto;iw,eesr, the puroiftthye PFOSA sample wouldbeapproximately 96 %(6 &
`appendix I).
StabilitDyo:cumentation willbekept on file with the Sponsor.
Storage`UCpoonndirtecieoinpst,: temperature.
test
material
will
be
stored
tightly
sealed
at
room
Characteristics:
( dIenffionrematthieotnesotnmastyenrtihaelsiwsil`lmbetehkoedsp,tcoonmpfoilseiwtiitohn tohreoStphoenrsocrh.aracteristicsthat
000154
2
: T-7132.2; ST-39
PFOSA PK
Animals:
Species:
Strain:
Source:
Rat
Sprague Dawley
Harlan
Age at initiation of treatment: Weight at initiation oftreatment: Number and sex: 30 males
6-8 weeks approximately 150-250g
Table 1 - Dose Group
[Grow -- [Dose
0 mg/kg
Smg/kg
TN
Truman
Seach on days 1,4
and 29 post dose Seach on days 1,4
and 29 post dose
Identification: AUA Number:
ear tag with animal number or `unique tail mark. 2246
Husbandry:
Housing:
All ratsfromgroups 1 and 2, whichareto be sacrificed onday 29 post
dose,
study
willbehoused
(see Table 2).
Winhdeinvindoutailnilynmemteatbaobloilsimsmcacgaegse,sthfeorseproarttsiwoinlsol fbtehe
sgtraonudparhdoucsageedsitnhsrtoaungdhaorudtcatgheess.tuAdyl.lotherratswillbe group housed in
Diet/Water:
`HTaerkllaadn,TMeakdliasdoLnM,-W4I8,5anMdoutsaep/wRaatterStweirlill`biezpabrloevDiidete,dstuoppalllieradtbsaydHalrilbaintum throughout the study.
Environment:
Entevmipreornamteunrteoafl7co2nt+ro3lsFf,orhutmhiedaintiyomfa3l0r-o7o0m%w,ilalbmeisneitmtuommoafin1t0aienxcahanges
of roomairper hourand a 12 hour light/darkcycle.
Dose and Dosing Procedures:
MethodAofsiangdlmeinSimsgt/rkagtidoons/eDoofsePFprOeSpAarwaitliobne: administered via oral gavage to
rats in group 2 onday zeroofthe study. The PFOSA will be prepared from
a stock solution of 100mg/ml PFOSA in acetone.A final 0.1% (1mg/ml)
uniform suspension (or emulsion) of PFOSA in 2% Tween 80 and 1%
5acmeltosnue swipllebnes/pirokengpabreoddyuwseiingaght1w5ilmlibdeoaudnmcienitsitsesrueedgrtiondeearc. h
A volume
rat. Re-
of
\
suspensionof
pestel before
esaoclhidssawmiplllebeispderrfaowrnme-duipwnitthheSsystrrionkgeeso.ffortdhoestiings.suAegsriinngdleer5
000155
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T-713P2.F2O;SSAT-P3K9 maldmikngisbtoerdeyd wvieaigorhatldgoasveoagfevethoiactles,i2n%groTupw1 eo8n0edaannyd2e1r%oaocftethoenest,uwdiy.llbe ObservaCtliionniocaflAOnbismearlvsa:tions: fi`Emnaodcrithnaglaisntiwymiaalnldbweimrolrbbieedoibtcsyeaarnvsodetdhneodrtyaaaiblryldee(oefbxiescnedlriuvnddegisdn.gwiwlel ebkeernedcsoradnedd.hoAldiddaiytsi)onfaolr Body WEeaigchhtasn:imal will be weighed immediately prior to treatment, weekly thereafter and immediately prior to euthanasia.
Specimen Collection:
UFrrienqeauenndcfyec(eSseceoltalbelceti2)o:nswillbemadeon days 1 - 4postdose.
Necwrillobepperfsormiedoendasys 1,4 and 29postdose.
Table 2 - Schedule
[Sen
TMOocn day0
Toe[0cstS [dayI1PD
W|[d0eaady62PDTr[|do0a7yn3PDT|o0|dcnatys4PDT|sdTaoyaetSsrPD]
DOSING | CDoyll1ecPtDion,| Collection | Collection| SCwoiytecchtitoon
Octo [oan
sDyc4PD
ie] [on i [| day 13PD |day 14PD|dayISPD |day16 BD.
03 [ous
Csr [0am
day 19PD [E]
day 27PD|day28D|aaDyy229970 PDs
MethodUotifnSepaencdifmeecnesCwoillllebceticoonl:lected from each metabolism cage at the dtdheeeisoiungrinizanetedecdwoalttliemeecrsta.inondTahtpehpeainrfiaitnitaaullsvvwooillluummbeeeoowffauusrrhiinenede wwwiiiltllhbbaeepprbrerocoxouirgdmheatdt,etlotyh1e55-sm1iid0emwsliotfh aandidmiatli.onaAltdethieondiezseidgnwaatteerd.tiDmaeis,lyanfeicmeaslswewiilglhtbewielultbheanriezceodrbdyedCfOo;r eaancdh wc8o1il0tl5hesocutnteedcanrvtoiiapcsotyahgepuelaarbnfdtoo.rmmieBndla.looaDdourrstiaamnapgnlndeesctrrwaiolnplssfybe,errbaelldoltooodweb(dl=ot6oodmcllc)ootlwlfielcoltariboenpetruiboeds
000156
s
:
T1322; 5739
PFOSAPK
of15 to 30minutesatroom acentrifugaet 1100x g for
Stmeimnpuetreast.urTehaendsetrheucmlwoitlwlibleltbreasnpsufnedrortweodnin
relmaboevleeda1.5nymrlmeicmrofaurgieetdbunlboeiosdanncedlglcse.ntEraicfuhgseedraagasinaat 2mw0i0pl0txhlegnteboe
transferred to a separate labeled polypropylene microfuge tube and frozen
ilnabderlyedicset.eriLlievesrasmpwlilelbbaegrseamnodveflda,shwferiogzheendi,nplliaqcueidd ninidtirvoigdeunaltlhyeinnto
maintained on dry ice.
Specimen Handling: S8p0ecCi.meFnosrmweitllabtoelmiptoeraanraillyysbies,stthoerseedsipnecaifrmeeenzsewrisleltbteopmaaciknteadiinn-d6r0ytioceand shipped to:
Kris Hansen, Ph.D.
3M 935
Environmental Bush Avenue
Technoloagndy
Safety
Services
St. Paul, MN 55133-3331
Ph: 612-778-6081, FAX: 612-778-6176.
All results wilbeprovided for inclusion in the final report.
`The number,type anddateof analysis are as follows:
collection
ofspecimens
tobe
generated
for
EA ial Table 3 - Specimens
`Specimen
dayl
post
[day2
post
|[pDoasty3
|[pdoasytd | |dpaosyt25 | Total
Serum
dose ldose |dose [dose |dose
(S/group/day
Feces (Slgroup/day Data Analysis: ADtoaNxtiOacoVckoiAlnleeatcnitdcedp/oaorrnaSmpteautrdeeenrntstsacnoTd-mtpfesootru.sntdataisntdiciadlelyntsiifginaibfliecmaenttadbioflfietreesncweislbebtewaeneanlygzreodupfsorusing
000157
5
a
: T1322; ST39.
Responsibilities:
PFOSAPK
tDicesoalsluneencstaiLpnguenckiceerifasonpmredaceniAamlnneydnssirs,se.pweSrefaocramtiwnigltlhbeenreecsrpoopnssiiebsleafnodrdcoolsliecntgitnhgeaanndimseanldsi,ng
KrAaenrvdiisreHewawbnesSfeeonar,cea3atfMwiiEnlanllvdrirerapofnotmraetnifitnaiallss,ruewepidol.rtbaenrdesepnosnusriebtlhefeorreapnoarltyrteicceailveevsaalpuaptrioopnroiaftteh5eM
000158
.
'
T1322, 5739
:
PFOSA PK
lotta Tp Andrew M. Seacat Ph.D.
STotxuidcyoDliorgeyctSoprecialist
Beodt
fonfry Date
DAedavnannaceLudeRbekseera,rcMhSToxicologist Study Toxicologist
-
`Sponsor Representative
Date 1/9
1/] ae
000159
,
ee
\ References:
T1322; 5T39 PFOSA PK.
I SpGeirsootsisccscimduema:unlaMantLieRov.analiunnadtoirBoaonllwoyfedeinxsptJor.siMbe.udt(ir1ao9tns9:,0)eMl.TiSim.isnsaTutheieoasnns,a,laynUsnidspooftfelntuioarlinfaotred sulfonamide
TGiAs.su(eadsiostproisbsuitbiloyn apnubdleilsihmeidnaast:ioGnroosfasmfalunorMianratkedRsaunlfdiovnB.aomowifdeGenepoJersMgti.iac,i(d1Ae9t9ihn0e)antss,.
Fundam. Appl. Toxicol, but notfound).
2 sGautrlsofsodsnumraiamningdMea.npRed,st,aifcMieidrsep.parJgo.elAlog,nrgMiecEd..FdoiaeontddaBrCyohewexmep.nos4Ju0rM,e.2t5(o01a59h9i-2g)hlDyisfturoirbiutnigotnesand issue in
2509.
3 HKSpuJemciaHfnaicnSsCeehrnaar,aSLcat.meApr.lieCzsal.teim3oenMnE,onfOMvLriEgr.aonnEimlcefnFitloaunlo,rLoHacbOh,e.mSitJ.coahPlnasusloi,nn.MGe(n1e99r5a)l.PCopoumlpaotiuonnd
N $5133
#
Payfer RM. No. $9426.
RGeOpoMrtS9/a2n4/a9l9y. s3oeMfs
SPAFO&SCALa(bL-B1u0i0l0d9i)n,g
2S3A6R.2C5.A1na1lytical
Request
.
5. NATnoMalmRyKteiScspatelncLetarrobCsohcreoamptyiocRrae/ylquCSheMasMrtDasc-t#2e3r56i9-z4a22tB6i-.o1no31f,MSSPpeFepcOtiSeamAlb,teyrLA2-d51,h0e01s09i999v,,ebsy4&1CHheamnidc1a9lFs-
6. (&DCoee1nRsto8er4o,.sBFRu.ieLlq.duieCnshgatr2a0c1At--e1Ir-iS2z19a2,t5i4Co.nAoTRfCePp-ForOCthSr1Ao0/mS7aa1tm9op9lg.erCsao,prhTpy-o7rG1ar3to2eu-pA1.ua(Ly-t1i0a0l09T)ecahnndolToNg-y
000160
5
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Li
Appendix I: tTetw7a35s0685
CarportsAnyiTachnogy Corte
T132P2F;OS5AT3P9K
To: Subject:
ALnadmryeAw. SWeeancdainUgS/-UCSo-rCpoorrpaotraet/e3rMsUMS/US Characterization of PFOSA Samplefo Toxicology
Lary,
fpo oauvned c5y ,o6m0p0lptepMdmootofhrePeH4F1PO9LS6),OtMh1a,S10cs0hpaprrapocpmtoeorsfiezdCattFioo1nb5eo5fu0tsh,eeNdPHfgFo,rOtSh1eA0asnpaimpmpmalleoff(oCTe-od7iF1n31g2-9s,ShL0y-N.10H01g0,8 C6/86F0108pH7pS0o2fNCHF31a6nHdSlOoZwNeHrzc,on2c4e,n0t0r0aptipomnsofofCsaevFe3raglHoStOheZrNaHm,id4e,s2.00Bapspemdoofn the sumofthe impurities, the purityofthe PFOSA sample would be approximate9l6y %. hvtnoeenratethliacotauitvgieohneatolftitothneismorcodoremerpaionbutonhudetcwahaprspoabmraaesntteogdprrpaermsi.emncaReraytohfoenCrtthFhagnoabCsHeFSrOvRe3sgNSHmsoOleicnutlhaerswaemipglhet, anTdhe odmtlohnreterifppcararottibiaaolbnllywehitlyhdarrteoqtguheiinrseactaoedmddptpoieournnfadlluioasrnaaoclatymusiaedlsel.y(1CaaiFs1o 7nSe0e2d)1,0 NtHh.nkCmoonrfiermasabtoNiuoptnw.ohfetthchieosrurthse.
s may actually beof this, ahaoadereoiPrnnRecaeOstnSatewmrdaatsaomnqiusdahenosui,lfdiweebdreeuasaiclnclgrqauatsaetn.ainfTdehaderduascmiunirgdveae iPpmrFpeuOprSatriAeedss,abnhyodawaneravdleyrcz,ainvignecPlauFsdOsinuSgmishntegapantdainanresdiso inamtbnrudroatdiruecdsessafrooemreeeameamacreshnmsaoofsrptoehcetihsaeeqlaurmaeisndpetosi.nsteaAfldtasiacot,vtotre,haissicdsatilhdceuPblFaeOtsSetdAw.peurcWtahyinalsedsotsuhiimsneacssewtshueamtpdolslisconof twfipesave. NSeeithnaylemrFpOolSfEet,hweaeatsnc.aalnaytaslcbeyolsznefceotednubotnyrHdaRPtviiLcooCklatPneeydolaerrseuedsmeiitnvegocltGaetCdi/beMyiSmtphauernidatbnileyys,sCieAs.T..,CWhuNsi-ilmneegntooyutiraFGOwGEma.esyiunes,e,
ns greater than 50 ppm. chrre meaosFteEaeOsSaIdAnmjperleoeuswtpaaossnfesomteouinqaduaPtnFoiOabteSiA1v1es8taa%sn.sdeaTrsdhsemcseunervteao.nfatlUhysseienpsg tuwheirsrtoeeftctchhynaeimqPuiFesoO,udStAhIenpbduyrutcpyotmipccarireaiinign HaGirvtamiteoitnoonfgarwctaoouprl,hcdtibiicnoentmshoeaisfvteheroaadcgeh1ds.qouluIatnrilgonte,nyesroaelit,aheihyovweselhvoyeuprk,iiebeimsartenleoarttiihavilegldhyluyaecatccoucrtauhtereaeaxttsteornewmaeeeylysl)arge t1iruamec,estunhaletpluyarhliitgvyhaweroriauttlhidaobnncewtahdoseeeutpd>eu1rrb0tmi0yis,n0ohf00et,hepthuParFttyOmuShsiAgtht.bheaHtawsppelpiaoerds.esiIubsteisntgnhaoatstteahxepstepaucnrtdteaydrotdf!hiaIer thseasmwpiles
ed to b>e 100%. hiheerccoaelecauSlteaoatnceastthhahteatshcreoenrvcaietenswireredacietoihvneioncfgonP3cFemOnitySrkawgti/ildoannsyotwoautdhlvederiismnpgleuysrttafiafepespct.tht0ah.te2w0setmrudegy.dPetF4e1rO5m.ia6ne0sd0 asnpdn,
00161
9
Coe T132P2F;OSSATP3K9
AppeInCondtiinuexd: 9BI2v8pedeorae(rywdbseaasicegsodhnotscne=unptrrm5eauavtiii0oon.uns2gf5netekhdgeirnaigtv.erst1fuwodiemefsu)trhatenhredersaiisvdsruiauslmeaPtpFhpOraSotwx3iom0ua%tleolbfyet12h2a0tg0isrudagemFp,osFinetGedtir0net3h,e12 monseoqutenaceosbf.PAFonOySlPAgFtiOo/SPsmFegoOrmaSsSr.pupraemd,wmhsic,hiIgn nseolfvisehroftuhladitncooctulIdmabpeosnasattniyoltnoxyuicoolgien S`mhoeeevtriaafcbleouvnoltrireiacntsaaittoettndaahscanpkt,dethtchehioeewr1seeovHfenardntodhwe2ns:eHtphaeemriifdnleeu,sosrahonaodumwlioddubelesdaannroaotlyiatnitmceaorlelusytnidnt0igsataisnoctrthfeersyeoemmaatryiobe.etosxiucb: jct to tAhensdtudriy.esiwl hiking abooruetwowuhleidhbeeratchce(epCtaaFb1le7i5f 0no)oNthkerswiulbhsaivteeacnaengbaetperropoamrsedon ptreoavisdeegaidvedimtoenaalcaInlflorama&t-i0o6n8,5ifyouhaveany questionsconceringour analysesorf | can cFatrLe. DeeRodos
000162
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