Document 8Ve2n09MpLp0GoppEdQ6103Mm

, . aannNdAfobisTsTeoioisrersptpstvMtuieaieononinDDniiissaasnetndtdrrziiBbaBboiitursoitittoiocrnonaannnofssaatnnodoNdrr-mEmEEaallhttiiyimimloioinnnnaaFtotoOiffiSooENNnn---IEEooCtftfhhyCCyilaalnrrPbbFFoOoOenSeSn-Ed-E1144 after Administration of N-Ethyl FOSE-14C in Feed JJaannuuaarcyy 1199,, 11998833 Conauctes Att Conducted At: Ductngs Miring: Conducted By: RReeppoorrtt BByy:: RReevviieewweedd BByy:: RRS3S1tiMnK.x'teCC!reoarnnucLtLteeaa,rbrboorrmaaittnoonrerisieoests,a, Tre. inc. ss144 SOctt.oPbearul,19M80innteosFoetbaru5a5r1y44 1981 October 1980 to February 1981 S. J. Gibson and J. D. Johnson ky] Colles 1/29/73 S5S.i.ntJ3.e.cGGiitbbasssooenrn.atory TechniciDaDnaattee Senior Laboratory Technician Jind Onder Raserloh Specialist T ~J. D. dFhnson, MS Resea h Specialist ou Yor /2 -1 , v Date (;~Fa~zv . 2. ober, 20 Date ( ( Row 1j27/83 MMRaa.nnaEag.geerOr,b,eDDrrr,uugPghMMDeettaabboolliissmm Date i | i| |ilIl ti i i k so i i I ii; ,I IIii;l I, ii 3M CONFITDASTHHTTIIAAL iI 3 [SE y| 4 ER & Sie Feat raesama ve Grass oT MMaaddee AAvvaaiillaabbllee bbyy 33MM ffoorr IInnssppeeccttiioonn aanndd CCooppyyiingng aass CCoonnffiiddeennttiiaall II nformation: Subject to Protective Order In Palmer v. 3M; No. C2-04-6309 2813 ExEhxihbibiitt 2813 | 3aMwAa1t0oo0s5a3n1e8s6 State of Minnesota v. 3M Co., Court File No. 27-CV-10-28862 281133..000011 oo 0:Z.- Table of Contents PPaaggee 5 Summary 1 IFnOtLrEoBdOuUcEtLiIoOnN +uiirsieisirirrsersrresssnsrirseressanss 1 Materials and Methods 1 Carbon-14 Labeled N-Ethyl FOSS 1 &.imais 2 Dosing 2 Preparation of Dose/Feed Mixture 2 Administration of Dose 2 Sample Collection 3 Radiometric Analyses 3 Sample Preparation for Radiometric -Analyses 3 Analyses of Samples 4 Isolation and Identification of Metabolites 4 Extraction 4 Column. Chromatography 4 Thin-Layer Chromatography of Column Fractions 5 Results and Discussion 5 Extent and Route of Excretion and Tissue Distribution 5 Isolation and Identification of Metabolites 8 References 10 List of Tables, Figures and Appendices 11 N3iMl coumENTIAL M Made Available by 3M for Inspection and Copying as Confidential Information: S`Suubbjjeecctt ttoo PPrrootteeccttiivvee OOrrddeerr IInn PPaallmmeervrv.. 33MM,, NNoo.. CC22--0044--66330099 22881133..00000022 3MA10053187 page 1 Page 1 Summary Summary AsASofuutrtllooeffsurcopnnsaaaasmosisifiiednnoosg3l)lee,eetthhooaaactrnnsoadllll)e)addsoo(mtcsmeeeeaa1no0nof1fddoNNoavnso-edece,,ttphir1y1)olC0b..FaF11Ob3O3SlSEy2rEr-a-.g1n,,1kdok43crCg)e)((tii21-hnn-NaNr-ff-eeeeetst7dthh0yvy]ltcooofppeeffraactfshsfetltleueuddctcrototrreoauantcltcststaannee- | CGcv"(aaaegmccrrriyhbyonoouannspriit-slo11oiuso4wosf;ni1s3sff)rorfoo,ainmbbecasot0o0ar-r-b3rlb3e7ee2bsad.odGs.aatnyyeEDs7,1l,0iiie8rnoo;innsainllnbnaydysacatk6pt6ior33on4o%n2b0o-aoooff3ffb0lccyttaahhfreremonlboodorodnenor--tseiht1ehda4atiinvsvs.ioifaa7ee0llsui8iuremmrioiiiinnnfnneaeea.tttehaeadennd.ddT.htoffeteeFFacceeR'ece_caaslsalfl-1isl5ife | oeflitmhienadtiisoanppoefaccaanrcbeon-f1r4onipslaasbmoautof20c-3a0rbfoonl-d1thfarotmofdayuri1 net.o of the disappearance from plasma of carbon-14 from day 1 to GTiv5e5r"55Xanmeatlaynseiteicoes otfheNepaetrhfyllusPtOoEoEctaLmeassiveivfaodnaftreensnliiovne.r vaIsn days. A metabolite of N-ethyl FOSE isolated from liver was day 16 is 7.5 The half-life day 16 is 7.5 aidddeinttiiotni,ed by identified by |i eaai nn9RoFoa-utNmhhMeeeTrrsZtRatmeneokatnelaabybmesoililciciett.eeasffrtrohomen Liver bee been seniovivel iseneifics ss perkivere- perfluorcoctanesulfonate anion. In addition, 'liver has been tentatively identified as perfluoro- octanesulfonamide. | Introtuction Introduction In asaition to being product sold by IW, Neethyd FOSS is 4 key inter | PoImTihnneneodisittaapahdhkhtedeeaeittssetitiinunuoeednysytththteoeeoofrfsppbFFrreoooioC.fndd-8guu60cNc07etta7eiitomopmhnenreytotladaoofsfuboFocOollotttRiihhsEsoeoemnrlr8d7bbdppeerrbccayouaisdanuou3ssccMeedtt,isstt.tN.hhe-eieoNtNttne-hhhpEyrrttle7ehehCeyFy-lOl2eeS0ssPFE7ttOOeeSrSircEsEssontoaoiifasfsiknFFeiisCCymm--pp88ioao00nrr7ttt7taaernnaraatctr-reee {| mpmTf0ehhe..tao.t80atsa.bp0b8ohoa)8lal)titietooetrfefesesNsNpo-toohsececotctrcshuhsupyrryhsaoltfffeFrPrONOooS-mSmeEeEa.FttT.ehCCry--lI8I0htt07Fy7OvdweSraoauoEnnu1lddldyadsnNNi-debbseeaettiehehnoxyxfyplpaleeFdFccFCdtOtC-ieSe8StddE0iETontvtvhihi(FeaaasCttyo-dsi6ipept0fooefsf7smesesiccircieboebnlnnlatettenadcijcppoonaoarmtsmthmmhwooSawaunnabyty)srsacotofrehe TBtbahilcackett,raaafrthtsacef.ororrsbnmpasahsotoirisopopnunhiaoootnffe, NeNo-sisetttetshrhuyyellhyPFdeOOirSaSoEtEleyiasavnnisddstiFFooCCfn--,F880C07-a7n8df0fo7ollbl(llosoowwyrsesstaienimmstiitilcoearsraaancdpri/aaootthnrhuwagoarfuyets.). the Thus, the absorption, tissue distribution, and biotransformation cf Wethyd RogE vece investigated. The resuite sre discussed in the context N-ethyl FOSE were investigated. The results are discussed in the context SSialooinhaetse:fivorohemicst metavolisn data. from FC-907 and perfisorcoctane- of other fiuorochemical metabolism data from FC-807 and perfluorooctane- sulfonate. Materials snd etrods Materials and Methods Cacbon=14 Labeled NoEthy) FoSE Carbon-14 Labeled N-Ethyl FOSE I po ' /C2H5 emiserasort op caon C7F15*CF2S02-N '_CH2CH2OH + DenotesFost ion of Casbon-14 Babel * Denotes Position of Carbon-14 Label NeBthyl FOSE ie 2--athy) perflsoccostanesulfonaridoo sulfonamid ethanol. ethanol. N-Ethyl FOSE is 2-N-ethyl perfluorooctane TThhheeeuccctaaicrrhbeoornn:--1144(olLn aabbteehlle sCthreumcitcuaret)h.ereOtntetrhiez ib1asssiaastt abtaisoins, ototfhfhaeendttchhceaearrrosbbsbopoplneneoccs0iiahfefintitcicoocatatslhchteetepiiasvssciiuuittllytffyuyurGrdeertteaaeetptrrooomammriitnne(a(adstsceeiieseocennpa.s,ub,hrooavveetely EcTT(7nhhe1eese7)'tm,iisssctppi.aehheelcecii(SctfNRr-hiiiaecackctrehharsayycichltttIieisTFvrvoOOiiitStSztoEyaEyp-te-1ooi11ffoS4CCnrt,vtehvhwneeeaastnsadl1rjooJytuturddaNoggOdueeffimddoNbNco-eshssreuuetitimthhti4ayyac0bllbal)lleFFe.OOp1SSufsfEorEoIrir-0It.1A4mym48CCee3ttrauaue=bsbspoeeoodlrld0iti.ess0iidm0nmn0sststtethhiuopeesddassiiereoeeasts.,e.ly TTsFTMohthisueegSduEa-irrf1eeaHa4ssdioCcico(1hdRcd-C5oiho)skesReiimLrnniaCggcuaIdaLslssoocoPhtlpleauouurtrptRiiiieetootaynInytnhdvd((yeeesslttneeeeteerroPAmmArPiipyOEnnpeaNaeSptuntIdimdiECioiboxnxenrvvew11as4a-s6s=8fTT)orfaaueebbnippldleseeeas0tttee.o11dd4,,8beoa3aonmnf{ddstttAAh0hppeeL.ppe0eaeNN2-snne0teddeittipxhhx9C8yyi0ll/11%m-=g. pure. Figures pure. 1-5) and the N-ethyl POSE-14C was found to be at least 988 3M CONFiZIIDAEEYNTIAL dW'iu9A 9' SMMuaabddjeeecAAtvvaatoiillPaarbbollteeecbbtyyiv33eMMOrffodorrerIInnIssnppeePccattiiioomnnevaarnn.dd3CCM,ooppyyNoii.nnggC2aa-ss0CC4oo-nn6ff3iidd0ee9nnttiiaall IInnffoorrmmaattiioonn: Subject to Protective Order In calmer v. 3M. No. C2-04-6309 22881133..00000033 33MMAA1100005533118888 Fae 2 Page 2 Animas Animals SMHiEiaannllddeeiivvCCwiihhddiaiuaenrarllliefsmsmaesettRtRaeiaildlvveewrmrrieeatttChaaCDtbDoofllrrriieaaoesttssms,a,ccceaeaeeigsinegegsshhsttftfooowwrreeweeak4k4ts58serohh01loo8uduf,rr,orsswvppee3rr4rreiieoohrcrocosonttntsdodoiitdtSpioierorsionioninereneddg:.btotooTThhee dwgvBroeaeoisrteyneisgndgdww.ooe.essiregeedhdTTthhfsaeeiisnntbobefgoogdrtdroyyorwuuaipptwwsetseehiioosgVfffhhirittse3hs3;ei;nrriaaainncncngdgcadeecieidhdvsvisisfdfdrrturuoaooa)mumlwpa2rr3t2a3oae0ft0trsstt3fwovooweere3rr3re2e2e209s4cge5wl,l,hieesoccmmhutteeireeaensddnnpg1sr2s+i7o7o3Go7rrttayhuhcta.oetoto tRttofahheeets GeCcEhbody each weights of rats within each group of 3 were within 91 grams notdherV.aterTheathreartecvoerse:alloed free sceess ic Pur inet Gross other. The rats were allowed free access to Purina-- Ground of Cht;a and water after dosing. poste Dosing ! Preparation Prep of sose/rect mixture FA2vP0nOolOSNiEN-amSe-eerg1Eatt4ChtWhyiiytliolihnnnFt1tOoOoosSfSbESaaiD--oo11l11 s44uCeClit/ietFstseeeooererlltduhuCCattllnMiiaoaooilssnnx,sstwwuAaaraAnssedvveoppmslrriseuexmppiaaantregreddicbrbbyyFliewwnceevkieisrggthhiiisnnnegggj.oNNn--teFeitrtshohsyyllto P1NPNvu-uoe5rerlttiiuhnSnmhyaaEe)liGG5wrrFiiFooOtaOuuhdSSnnEEddf--aoTb1CrCAs4hChCoooolsnwwsueootlwlweueuahstetosiuitrooha1nnda6ddntewvehosaeadl.rns., tattTTnrrrhhdaaaeennnmsssNfifNf-eoxeemernirrerttrnrtehheegrdyyddidlcbtySvFfRoooOOliSSanaaaEEvs.-4e4sk1rl,el4et3Ciagi1m/tsdnfejgaeru.ttesrdtebbTyieehnamckgkieoeennrrteioonaaisnhnedd meTSwGoitiaipxxhnsettaanniunscarrothieelixrwwUwraaaeaegds-dfedeaeovvetraasteppetroooeermnrnaiiaetnnt1eeehe:dddod.u.rbbyyTTtchhhcoeeeomnncbvcautearsrrrbtatooinoosnnnf-1e14r4(rccecedooennttAtepeonpnteatnaogoiflfsatsch3hseetndrsgoaosyneem/raifbnxdeeteeusdtrhee ion (see Appendix 2 and AAepnpienntdsitxra2t-ioTnaboflevo1s)e. Administration of Dose EawEavdanniaiocczrsheheeiinnfttfvddaooaiaissv5vttittiehahdcedeeuoavnilrecinaiantmmsgtseheiitetdwdwadeaaealltsoomffmmwwoeeeeeieuttiagagaanhcchbbehheooddollfcciiaassiiPggmmmmeuemmcrceaiaatdtdgngoioieeean.h.tthGoeeorllllodydyAAufnbtfbedeehaeeeffddCoohrsrcioeecnuwuapbpbleceeiwwioennansggotsraatiaotlnrttriatiananendgccssehhffveeee5esdr.rr5r3ewew1idditnte1hhttgoo hHdN11o-o,:eue7ss2t2ee.h,ywp)alaaensPrnFdOiOaoS4S4.ESw-Gde-aai14yyFg4csCoshr/e)pdgg.oo.rssaatttmsdAAdooLolussLlnseeatocofcocfrofoinntftPssihhuucueeremmdeeircddnaatatsattstGhhreei8i,onndudonott1tssdhh6h,eeeeeChsgaoSmiorndcianoomwugiuncsnlp5ioeie2snsssosttdetaeaurccrriaetreenlr:diffpndiiegoi-inrsn:net0eesadd.a.c5r3taabe1Twtti,ohoemg= lRahSSeoloo1ytnunEhrggkodeeouorripgsgehheepr/eirSmmroieiodeoeos.tdddt FoomoooffffirxtttStuhiihrrnmeeaeeetfsCawnvassoaastatstsecedrscasiollfrnlifimaoaocwtutveeemesdddedaatttateeovtoatc8stcohn,oneevnse1fui6fsseme,eheuedodas/tntdddhhooeeasn3sedded2.oovdsiteeahem'meyme(esw1dd1e5ipi2lsoaohstehnoetoeeuludnsyorye.ss]e), a sAtSiiunhinrebybsattppdrereccoaaacttscctisetti.o/eeonfddn,e,Tfefhrdiireottommmdiasotxptprhhtpeeeueeraatretioaosrlttniaaontlttlihhsdcaadtototoesnsrvesveee/ue/drfmrfeyeeyseedldadLciwihtmmtaititsxlxlfieatewtuueoriorfegfevhaesgtgtdiihhveveceeaafnnnlfedceetuetdtlodohavwteeeoeaaarsccswhhessfiprrpgsieoiahtlnltt.ll.eesdhdeBByybbyy tJRwhRoeIreiSegHnrhEaatttxoosff.3ffTeoheoedd consumed. The mean dose vi 10.13 RNG. (ver dose administered each rat was calculated from consumed. The mean dose was 10.13 mg/kg (see the Appendix 3). Eab CcrhurareircntlaeesstRRaiibvveeCrrhoBwB,rreeoeRsdaiilnnsggtonLLaaPbvuoorrriaanctaoorrCsioeerms,p,anWWyii,llsmiiSnensegttooonnv,,isMH,aassssHaiacschmhuousoseretitt:tss.. Purina Lab Chow, Ralston Purina Company, St. Louis, Missouri. - 3M CCHpFEIIDnTETITIAL ;o MSMuaabddjeeecAAtvvataoiillPaarbbollteeecbbtyyiv33eMMOrffodorrerIInnIssnppeePccattliioomnneaarvnn.dd3CCM,ooppyyNoii.nnggC2aa.ss0CC4oo-nn6ff3iidd0ee9nnttiiaall IInnffoorrmmaattiioonn: Subject to Protective Order In Palmer v. 3M, No. C2-04-6309 22881133..00000044 33MMAA1100005533118899 Page 3 ti I Sample Collection eine and feces were collected at 24 hes intecvals for each car | Urine and feces were collected at 24 hair intervals for each rat I sacrificed at 1, 2, 4, and 8 days postdose (grcups of 3). Urine and feces were collected at intervals and respectively pooled for each rat sacrificed at 16 and 32 days postdose (groups of 3). At 1, 2, 4, 8, 16, and 32 days postdose, rats were anesthetized iwimimtmmheedddiiiaaettteelhlyyylttreratannhsseffree;rrrrbeelddoodttoowaaashhdeerppaaarwrininniifzreodm zed the descending aorta and vVaeccuuttaaiinneerre ttube. Plasma ube. Plasma i was prepared promptly by centrifugation. The rats wE:e sacrificed by exsanguination and liver, spleen, kidneys, and lungs were collected as whole organs. Bone marrow was obtained from the femurs rnd tibias by splitting the ttaarreedd ccoommbbuussttiioonn ppaaddssS!.. bones and collecting the SSaammpplleess ooff ssuubbccuuttaanneeoouuss marrow on nieces and `abdominal of and abdominal fat, and muscle were collected. Digestive tract (esophagus, stomach, and intestines) and the remaining carcass were collected from rats sacrificed at 1 and 2 days postdose. Radiometric Analyses Sample Preparation for Radiometric Analyses Feces and major organs were prepared for carbon-14 analysis by hemoganizing and bbuussttiioonn ccoonneessa-., aliquoting a HHoommooggeenniizziinngg wsvaaassmpddlooennoeefiintnhWWeaarrhiionnmggogbeblnleaentdee:isntobycom- adding nine parts of water to one part of nders by biological material. The homogenates were weighed into combustion cones in duplicate by taring the cone and adding 1.0 g of the homogenate. Care was taken to mix the homogenate between samplings. Samples of bone marrow, fat and red blood cells were weighed into combustion cones. Care was taken to weigh these samples promptly to avoid loss of weight by drying. Homogenates and samples weighed directly were combusted with a Packard Model 306 Oxidizer Recovery of cartoon-14 from biological samples was determined by combusting suitable blank homogenates (feces, liver, kidney, muscle, and spleen) spiked with N-ethyl FOSE-14C solution; these reference samples were combusted at the beginning, middle, and end of the experimental ~'ample set (see Appendix 4). Urine collections were sampled before freezing ano were counted directly; duplicate 1.0 ml aliquots of each sample were pipetted directly into scintillation vials and 15 ml Aquasole was added. Plasma was sampled before freezing and counted directly; duplicate 1.0 ml aliquots or 0.5 ml aliquots plus 0.5 ml water were pipetted directly into scintillation vials and 15 ml Aquasole added. All samples were cold and dark adapted before counting. 2a Ppaacckkaerrd IInnssttrruummeenntt CCoommppaannyy., IInncc..,, 22220000 WWaarrrreennvviillllee RRooaadd,, DDoowwnneerrss GGrroovvee,, Illinois. Lc . . 3M CONFIDENTlIHAALL Made Available by 3M for Inspection and Copying as Confidential Information: SSuubbjjeecctt ttoo PPrrootteeccttiivvee OOrrddeerr IInn PPaallmmeervrv.. 33MM,, NNoo..CC22--0044--66330099 28133..00005 3MA10053190 Pace 4 Asniyses of semples Analyses of Samples AA5l38l5TrsaeaddiiiCoommoeerctbsriicLcigmmeeeiaasasvurrseec:mirenentnt(ts1s1avwteeirreoenddooSnpneeectuurssoiimnneggtePPraascc.kkaarrddToHYrooddpeelllarm33e336800andaanndd s3uEuSaor3rmmii8npnp5GelealTcerhsaiwawm-emsapCepsalalredercgseseoetteeccLrrooiannmuuqdiniunntniteedeerddddeSccdobGbiuiiyynnrrteteaaciicddtnltddlgliliy.anny,gtg,iot&AtanfhhteekKSennrpcocoewoowncuuetnnarttcaaioihmmnnmooggeuustnniteetezrfflsofofef.fiicciiviiFeeannonnsttrcceeyycrronpnrfalaftolaolerrecmsstatteeeaaaadnnccadhdhnadafrroddr ttbtCEhahoaneecmc-kpeigiCaca:ecazaoshroc:,ub:bnosnocdandnom-1wuwp14inil4ttteihhccnooagnnnttdtthheeeeennfrttfaeaipcpcopoopiffrureoonnepptecorraiycciinhhaagtt.feessoraabmmAbplfpellatslaecneenhrkksvswaesasaaasacnnsdhdccsaallfelsfacoocTruruw.lelrasccaltooteeuueGdnnwed.ttia.iiesnrngngFcFiooonrrreserfEdecftccoiiotcmcbmeiybibdeuuenssnucftstcyoeeey,rdd, LsotTfahhimeeeptTdlhSheeeiexcsttAo,AoeRrrESncnSs.aoae)ull((neAntcsusctittttenaooadgnmmndaateSattafairirfmcdciip,EEclxxie=attesenekkrcrnninyononawwalnnfltohSSreaattmmaaegoonnauruancdonsthatuczpddoso)f)fa(mSrcpiihaalnrrtetetteideecroownnawaaismmltleehtdtheshsottorodeaadv.rnn.mddiaaAnrTrTSeddoodvcwrcuaaaableysltiiibbourrssaaettee . ScaaTionndhnadmdebbeoduothssxhriitrteedeeossidezseewWssri:iai.tPtmmhpehpltleTeehhrhdiis,seg,hhsseaaamrcccpaarotolteirrecicrrososeevs)cec)irttniiiaaeoontnsnnddhetvwwteehgahrserseesormmeeuaapbddsasease(aemtsdpfphflolrorereecsesntthhvwwreeieeertrfehererereleccrronoeoewccvvcoeeeourrAunyyEnstStaeefmfdrrdrp.ca.alrmte.isoFFsoorr 4. I: Ctohneboosxtieddizweiri.h each sample set (vee Appendix 4 - Tables These recoveries were based c- reference ix 4 - Tables 1-h). samples 1-4). combusted with each sample set (bee Append Isoration sna Tgentification of Metabolites ; Isolation and Identification of Metabolites EExxttraaaccttiioonn AAGallyiisqquuooatftstserooffGottrhhieeng99::1v1erhheoommoopoggoeelnneaadtt,eess dS7alyasctadfteofr d1o,s05i3ngugwersequipvoaolleendt.s Toohffelliiavvleeirrquofftoosrr rr(aabttysswsesaiascchrrtii)ffiiccceoedndtaaaittne22d TofheNoaelsihqyuhotFsOS(Eb-yTiwCe.ighTth)ecohnotwaa-ined SSgtaTreer7antna3caoca0tt0tttieaie2olo1nvnwsaosasfsacncedfeS1xX,ttt0ttTrhhh5eAaee2CcR'teefaAetieg:ddnr:aee_isqttruhheirvwwsievioettealhhulmetfeniwwiatmnatoseetefsesror.vf.wvaiitNtteT-hThrhehteedShviLyaefefslttiihhnnFyyaa1Ollll,S2E0evev0t-otohhll1meeuu4irCrmm.ee.wwooiifTttTfhhhheeetbtbhahaheeccetorkkrhmeorvew-eaaxxvrcs-es TTeeT1hvohv,reaea5pp0owo0waarrnataatmetthelreoersudarnli.daaaannyysdeetrrTh'ehtcvewhhaefaesiwsanrrtaeeaaelssccriiiidddvdviiculfefleeiiuveeemvwddreaasswvowiefirrcsteehhwdaaiti22tshs5e5sesr0no0ollevmmwv1xealetdsrOofaf1incn,t211emn000dee880tthHmhtKaClwCaoLn.nloollataTnnidhdz((eeFFsssrrtetaaitviccrihrttrteriihereooddnnwa11)s).. SBdfdTh'ioile_irs'eesstcocaFhilniyhvvlleethesdeeorttuhhriieed.nnrar.mr.neeTeththTTehvahhaanesenwooaletleeettxrhht((eerFFrralrrcaaaevvwccaaetatdsrisiootnenwewvavoa2s2a1p)p;ot.otrhiraenaTetTntshehedeedexwitawwatnrnaahddtateecrrttStehhhdewvelaaostsrorweeffossfoiiiirlddtlmtuuitoeeememrereevewstdadahsswaaianntnrrcdhdeol-- | vt11ah:2s1e (frWivel/drtvi.es)rs.oclTTvaehhkdeee was extracted two times with chloroform-methanol cinhlmoertohfeonrond-ne(tFhraancctliovnas3).evaporated and the residue chlorcform-methanol was evaporated and the residue 1 i was redissolved in methanol (Fraction 3). column Cheematogeapty Column Chromatography Th5gthe0errl1gae8ece1ti02n2i..o0a0anccccmaohhfllooiirnrnLooivdffaeiootrarrammmmevetsetaelrelrureurrercccyyooh.l.leuuommmnTTnashhsteeowswetrterhhazrepreeheeeeppdaafccfrkkrbeaeyaddccttpiitltoooaonncssi44n00gffcrcrtmonohmmewvtiithtthehehextsrsaiiclltiiccoaan } 5ecthTxhhhl.eetlo5rora0rcCocooof0tlflouiuorm2mors1nnnm..ooaafnfndEEdaaelccniawhhvlaseoshrrhcciiooonnltwlgugoeimmrnnmeii-ttvscwaehaiistrsnnhottaeomoenlalcutttutdhhtoeeeegddr1:abb1iepweddihtte(hwhdwvii/tt5bS)hh00y00pa&EBmllllassocmmaiaoaotlnfflelglCCBB8taw)E'hmm,L1ooeyuu3nnaet(ntx(dEtEolrolffuasacattteeon A5510)505,0d2m5r10li0eoorffmslsmeoaetrftdhhacanhnroloetoldrio(gEfsEhcoluiruavmace-tasneeCCtiJ)hn..amneoTTtlhhheae1n:1onnliin(neevan/dfvfr)raatcch(tteEiinloounnaasstneawiwBeyer)zreee,deaevfnvdoaaxppoorrastteeds Carbon-1d content. to dryness oral redissolved in methanol and then, analyzed for carbon-14 content. 2a UUCnontmiepsraisnl,y,,saccTttniievv.aatteeWddillssiiiailmiisccpiioccrtaa,cciiddPe1m10s000y//l11v22e00nimmeee.sshh,, Clarrkkssoonn Cla Chemiccaall chemi Company, Inc., Williamsport, Pennsylvania. 3M SCHFIEESILLTNITAIALL W WL~i~d ~ffiiuiii3 1JL~iA SMMuaabddjeeecAAtvvataoiillPaarbbollteeecbbtyyiv33eMMOrffdoorrerIInnIssnppeePccattliioomnneaarvnn.dd3CMC,ooppyNyoii.nngg2a-ass04CC-oonn6ff3ii0ddee9nnttiiaall IInnffoorrmmaattiioonn:: Subject to Protective Order In calmer v. 3M. No. C2-04-6309 22881133..00000066 3MA10053191 3MA10053191 Thin-Layer Chromatography of Column Fractions - EmiEmaeaegctcthhhhaaannonooffogllttehheSetelluutstshiiiieoxxonn)c)cmooalwlrwuueermrmreninealfasfrservasaaeaccyrytteseiiddoonnsssbbtyyrtetnhtthhkaahiettindn.-ccclolooaninnytyteaeapririrnnoeeccsddhhdrrrcocooaammrcraabbtbteoooorsnngsc--ra11apd4pshhiy(yl(..ninocoattSSmgmaealllll sFSiaponolllltliaaovvqtteeueennossstttdAcsisanaioyntyndfssaittletteitnhnhhm.eete.iopmpnT"lalThtaaheettverieelisspplallelawvateteecrewrseoeesnrtedwdwaeeerivsrveneteeilrlnoetotghpapheekeendemdn,dettstshocoocanrrnaa11oppp55lerecddec-mnaainidinenisnno001r.t.t.bh555heeecncmst1aseeslssoleefieecglgctmimtaeeceedndanttsgsel ji timsV2inoic0otodt6nnoii1vfciis1vvceceiiyddaiallnssstpGecieriwvlnearltrcsateeeti1gil1mccol1eoona0nuun0tnnvt2tt~--eeeaddxlwwpsaarssaaecnnrdodaasnddettddtdeahehdieed.n.aidcdnaagTtTtpeahheeemrvecweecetcrnrohoetennattnceeocoafnnlalttlcsseatusnolidtooaafafttl7ee.ttddhhc5eeamraalbsnnsdecdeoniif-nrnritaeadaididliliololonaa---the |ij Fate. activity plate. per segment expressed as percent of total carbon-14 on the iS d Recoite ent Discussion Results and Discussion Extent and Route of Excretion and Tissue Distribution | Extent and Route of Excretion and Tissue Distribution TFTrT0hhho5eeesFz.odrr-iae1adts4gcaCuuliaattfdedsrmmoiniiinnnniidadssniittacceeiaaryrtteeeeeeddstthihiaannotftffeaafeteeetddcellsetteaooassftpoptrrre7e7v0v0iii%1ncocouuoiffsevlliyydaaunnfafalooasrrstaatfeleladdtecdoorassastetersesooffsiisshNNo-easweebsttssohhoiryynrbllbeedd.. i TTdTdTahaaahtebtbeaslaleeedaffdoto11rroa,,tattftthorhoeeottaarmaledldaaoetneetxaaaxxcpclfrrryfoeeesorrtstesiiseoouudnnorrfiin(ns(sfefefeeecccacseeoenmtsmsaesliipvpyfoolelstroeueieessvienauusrdrrcieeiipnnveesreis]hc)dheouonwaAavtnrreleeoriifsnncahhtToosToawwasnbnbaellreeeiinne2xs2T,chT,aroabewbaatnllnnedeeddi.3tn3t.h.hee (fhe | TddpheaarettiaasoedaadrraeeitnallAiipscaptkreeeendddeixaaxspsrev5bggss-eeeTdqqauubiialvvseaasllceeunnm1 ttusslaantdNK-i-eve2tet1.hhyyphleArsFFcOOeSSnsEEht-a-Iwo1nSf4CCdieeonxxsccTerarebeelttxeeecddre2,ptpeeercedx.cttriiem(neteTihoen | opo3C<ffea3.rr.0itb0t0o8ooodnttoa-oalff1li4nctctAahahipsrerepbbedooG2non0nod:s-n-3ie1e10x44i1v5s5viio-eaacllaiTiiuumarnrribaiiinlnrnnaeaeeettseeeiiddxss1tvevnaninnioodasattiveuu2erexr)xiti.tnneeterenh.sA.sainsivveTTsee:hhh;leeoiwnbbfnyyifenoc3eic3aatn22lliTdodaanaeebyylllsisviemimppiaioon2nsas,astttrtdeiidionxoooescnnssere,oe,offtion | i cahFsSabohocroraowubenuetvsotveinere-6r6,00,.118t4ittnoohhieffees te2etihxn0hxeet-tee3fnddn0etooatrsfseooeeodlffdbbccyyraamacr3vo3ebbr22ooendnGf-aa-ee1ydyx14ets4eaenplplsooniiissonmtvtnidiedanonobasaesttetohei.ira.obonnenTdeThlhvvceiieioamamiggpnafafoaseseutttccnirreedosoosniinwnidhtstovieeicssasEhtttliiiunldnrlaolailclnsooenn;llnyyet i| eeStaaxExfrffcfcaferernececescttttti.ieitdototnhntheebiymrrearaatattteathieeenooffofoNfaf-serrtteaashexttaydecsclrreeiriTttnanOiitSootstEnnhh-fii1esogod4ffCsctfeafueue(dcdcnsyeyeoessenai1Abis61psssponner<oConb33rrd0e0mmidaaxlhlhcoooauu7amnrnrdspdsaonudd(d(no2o2Ade)e).ss.pwphnnaiTToorcththaheetsSedfefeoee7emmeccsa=atlltoonotbbee TT4aaa8fbbflhleeoecutre11sd))..pbyoTTuhhtteedhoecmmeNee-aaennftochrcuyummltushleFlaaOttSgiirEvvo-eue1p4sCppeeror(fccseeenne3ttArpoaopcffeendddooSisvaxceerie7efxxiccacrnreededttAeepddaptevvni2idaidfxfaeeec7c,ee-ss bbyy | GSd4aai8yynasch,,eouaracnsnadarbp8oo8nsd-td1aad4yyoesseLpepfvoooessrlttsddoottshfeeeouvgnwdarasosuip2n2s88..f1oe1,fc,es31144..ra4ta4,t,s4a6annsddahcoru11ir55fs..i72,co,edrreleasastppteeer2ccttiditvaivetyeleslyr,y..4a sSaaSCiibibunsnnenosoigcrlrllebebaeeetcddiooavrrreaabaalnnolddpnedd-rtoot1chshs4eeeeennnlteiievssexoexfcmlmcrosordeesettftteeoeeduldlniidkrekfeaxeatcllithryyhneeetrrftteeoodtcthherravaseennipparraeeutsssnnfea4eaanbn8cbtseteoshomrmorbaabufetterodeedsmrricoicaoraColmlimplnaeoattnuthhneaoadrdftt,,dhahtoatfahrhssteeienrbbgeeeaennto cumulative percent of dose excreted via feces from time of dosing to 8 hours postdose 14-20%) is the Sper Linde cf the sstisate for 48 hours postdose (ti14-288) is the upper limit of the estimate for PSeErRcreenttnyohf 7dGoEe-TnEoCt vaabnaorabbesdo.rbedT.hue, at least 70 percent of the dose percent of dose not absorbed. Thus, at least 70 percent of the dose of N-ethyl POSE-14C was absorbed. TaTiGhhnhneeaoelu1ypdydzeaiieeggddeeofssfttfioiotvrraveteeccatCarsrrrabaabccoctrtnoeis-nf1ei(4(ceececssdoooonnpptthhaetaeagngnutut2s4s,,ffoaorsrnstdtooiimmn4naaddcciihhvvh,i,oidudoruaansnanldldporiirsanantttttdseeeosssttiieinin.nneeeesaas)cTc)hhhewvooeeffrrreeetsthcheiets Ng(po:peeoerturchpceynes.tn.otfCooSffrEadtdsoossqseuse)ia)vcaaralrirefeenitcsssehh,dooawwnnaotfiinn24`TTeaaabbnslldeee4484i..nhAopu((pTrhehsonedpidodxasrtitaad6.o)saserre.eFeeecxTxepphsrreeessdrssaeeetsddaulta3fss6romv5g3 TTCNaa-abberltlbeheoyn_1|14ff%ooSrrcEontttehheqeenssuteeiv6aoflreranafttteessce/s9aarroeepflurr'see.pp'dee.sianltgtueeeeddstiiinivnnAeTpFaaptbberllnaeedcti4x4.v.6it.hTT)hhceeFoemnmceteeaaesnnntsdttaootttiaeaallf2r8.o2m1 c50o11fa" rbttthhhoeeen-dad1oio4sgsceueoscnaaitttvee2n24ttohrhfoaocuuftrrsesscpueptosossitp4c8dlouosssheeo.ds.eisgHeBsoopwtwoeienvvvteederor,st,ertathccheoetnttiwaiisistshnssuece&sosnmteaawnendndntccosfoonnitts1ee1nn3.t48t%s.s32 o2f 26the ode, and digestive tirnaccetstahte 4t6ranhsoiusrstipnoestodfoseracceontLaoinfasatemreanthoafn 4811.48 mf t'r lose, and since the transit time of rats is faster than 48 2BRaAnnsaElltteeTcchh,,677,55 BBlluu2ee5.GH2ee'ngn 7DDrr0ii,vvee,,1.N0N1eevwaa9crkDk,i,sDeDeecllhaaywwlaarrFeeo..R? and 2.8 1 toluene. Hodified TSS: 25.2 g PPO, 1.01 g Dimethyl POPOP, and 3.8 1 toluene. SMMuaabddjeeecAAtvvaafoiillPaarbbollteeecbbtyyiv33eMMOrffodorrerIInnIssnppeePccattilioomnneaarvnn.dd3CMC,ooppyNyoii.nnggC2aa:ss0CC4oo-nn6ff3iidd0ee9nnttiiaall IInnffoorrmmaattiioonn: Subject to Protective Order In calmer v. 3M, No. C2-04-6309 22881133..00000077 3MA10053192 3MA10053192 reo Page 6 heute vith normal cates of excretion (see Avpendix 7 and Appendix 7 = hours with normal rates of excretion (see Appendix 7 and Appendix 7 Tobie D1 1% tn probable. that the 11.45 of the dose oboecees ot 18 Table 1), it is probable that the 11.48 of the dose observed at 48 hhoouurrss iiss nnoott uunnaabbseonrrbbeedd NN--eetthhyyll FF0OS9Zc--T144CC;; tthhee 1111..4418 ooff tthhee ddoossee Ticks Comrives corvoncta Lobeies moter el srsociated vith she likely comprises carbon-14 labeled material associated with the TE hiere tract and carsano1e Sanat material in ho tissues of the digestive tract and carbon-14 labeled material in the Eeces'ias Festi oF haorprion of hovteyi FORR-1 ic with ibsscuent feces as a result of absorption of N-ethyl FOSE-14C with subsequent Cinna ion via tie. Ie Teliove thot seme of ihe carbo1n4 on fuses elimination via bile. It follows tnat some of the carbon-14 in feces Eee iE Tones Lo Likely scserves Weck Polo 4C ag then sxcroved before 48 hours is likely absorbed N-ethyl FOSE-14C and then excreted Noein Tos Serive rotkrinss Fron the station of Mey: N-ethyl POSE derived material. Thus, the absorption of N-ethy: a nsy renter then 08. SE-140 is probably greater than 708. Ihe cesses of amaiyaes of Liver, spleen, kidneys, lunge, and red The results of analyses of liver, spleen, kidneys, lungs, and red ij Thee Cutie oe Tartans convent by combustion asd fon corven-14 in | blood cells for carbon-14 content by combustion and for carbon-14 in Shaina hr Sikes coomeing sre thom in Tobie 3 for inaivioess Tats In plasma by direct counting are shown in Table 5 for individual rats in Til aroupe. ihe gata ate exprevsed ag percent of dese): Also all groups. (The data are expressed as percent of dose). Also Treaties 12 Tonle 5 are esoich of anaivies. for catbonc1d content of inclr ed in Table 5 are results of analyses for carbon-14 content of lietive Tract ans Sotcuus SF rave sebritices or 36 and 46 noors digestive tract and carcass of rats sacrificed at 24 and 48 hours Somvaasn; `Foe dors seen avatyces of Tvs. splean, Kionert. Bans, postdoze. The data from analyses of liver, spleen, kidneys, lungs, Te tend exties Fister bone' sasren: Sisestive rac: seechsh: red blood cells, plasma, bone marrow, digestive tract, carcass, Coveitureoss fob, speninus far, and mereie are noreeiivas to 5 subcutaneous fat, abdominal fat, and muscle are normalized to a sara dove and are shorn in Fable & 0 33 hocuned FORE: Tig 10 roa/kg dose and are shown in Table 6 os vg N-ethyl FOSE-14C Suiasiniass of sibs [The sme Gace (nt notnelized ace Hered equivalents/9 of tissue. [The same data (not normalized) are listed pit in Appendix 81. Wean totes. recovery of radlouctivity from rate sacrificed at 2 boss Mean total recovery of radioactivity from rats sacrificed at 24 hours a hoses on Se amount tisese Caste 3) `oe mont. excrete and 48 hours [stun of amount in tissue ("'able 5) and amount excreted arte 37) as Ber. Since a corraction for retovers From the. commastion (Table 3)) was 868. Since a correction for recovery from the combustion aoaivees ab sages thete sevsiss seen Lowe Iu be Froperis shar Some analyses was made, these results seem low. It is probable that some Ee Nosinyt Pos1ei and/or te metabolites vere ions during of the N-ethyl FOSE-14C and/or its metabolites were lost during Preparation of the samples (het) FOIE IAC be shiney velatile ox preparation of the samples (N-ethyl FOSE-14C is slightly volatile at Fer esperatucer. Foon Taste 5 it ia sopacent that su vith FE-007 room temperature). From Table 5, it iz apparent that as with FC-807 7 porosiiun pekEiusrooctamssitonate (4; and saoanoim perCivore. (3), potassium perfluorooctanesulfon.ate (4), and ammonium perfluoroaotintate (51 a slams iomms portion. Imesh 5.50) of ne dove of octanoate (5) a significant portion ?mean, 4.58) cf the dose of Corhoncid ie ateines In the tives at 33 dave after slope oral dose carbon-14 is retained in the liver at 32 days after a single oral dose CE ihe abated compound. Fre sean Jos arbanctd Saved. taovmeiises re of the labeled compound. The mean loo carbon-14 levels (normalized to 1 Ra ts daves Th Aver ma harea- te Plovied vesees time bn Fivers 1 a 10 na/kg dose) in liver and plasma are plotted versus time in Figure 1 fot raves of Sate. (3 Tavs Groupl. The zetie, (ives/plam) of for groups of rats (3 rats/group). The ratio (liver/plasma) of CoraEne seveie are Biota vecuue tine in Figure 3. Feem Fissre 2, carbon.-14 levels are plotted versus time in Figure 2. From Figure 2, Ee ie aiparens shat the Liver/piamma totic La sot constant nd the it is apparent that the liver/plasma ratio is not constant and the Cullis 1s oe eotabliohed anid 16 dave Fortier. Selective equilibrium is not established until 16 days postdose. Selective Tevention of a bitenstoration product in the Liver vith nore 1opid retention of a biotransformation product in the liver with more rapid Chevrincs of Resihk `ToRE_Ti ardor snes metabolises vould be 5 clearance of N-ethyl FOSE-14C and/or other metabolites would be a Tossitie opal for this Petters ax 33 seve siver a sinpie crs} possible explanation for this pattern. At 32 days after a single oral rae of Kovihyh TORE- 1, the een aiver laine, spieensFiacmn ane dose of N-ethv: FOSE-14C, the mean liver/plasma, spleen/plasma, and Sone macros Pisces atbob-H4 Loves FELCH vere Toby Sree and Dt: bone marrow/plasma carbon-14 level ratios were 11.8, C.4, and 0.4, Tevpectiveiy, Ae 154 cage after sivgie by doen of FO-H0T-14C, the respectively. At 124 days after a single iv dose of FC-807-14C, the ER Sivetioc, sFieen/eiaima: and Cone marron/bloems carboni1s mean liver/plasma, spleen/plasma, and bone marrow/plasma carbon-14 Tooes Turion wee 2501: 20018, abd 46eT, cerpectively. Thue the level ratios were 22.1, 202.8, and 48.1, respectively. Thus, the oTtber ot autitioatian of carson th atker Foeso1TX- sentaiusiasion pattern of distribution of carbon-14 after FC-B07-14C administration Eee farent ren che acters after nostihTORE 1G saniniatin is so different from the pattern after N-ethyl FOSE-14C administra- 33% ~i~f~ CPOREFBIENNTIAL ~$Y it~Y~1{Y1JI~N~ ~ MMaaddee AAvvaaialabbllee obyy 33MM foorr IInnssppeeccttioonn aanndd CCooppyyiinngg aass CCoonnffiiddeennttiiaall IInnffoorrmmaattiioonn: SSuubbjjeecctt ttoo PPrrootteeccitiivvee OOrrddeerr IInn cPaallmmeervrv.. 33MM,, NNoo.. CC22--0044--66330099 28133..00008 MAt00s3163 3MA10053193 -- Page 7 ton thas despise the to d5ctarenhtesiounesofofhiepisniuspterratmiaonn (frosat tion that deapite the two different routes of administration (oral TTS LH 1 Srebiie shat reco biotramtorne- verses iv) and the difference in duration of the experiments (time toons simple conversion to Aoethyl FOR by from dosing to sacrifice), it is probable that FC-807 biotransformaeeimmaen so iin mbps biotrans= tion is more complex than a simple conversion to N-ethyl FOSE by Theres sino ae woes Tove hydrolysis of the phosphorus-oxygen bond with subsequent biotrans- formation of the released alcohol as N-ethyl FOSS. nT e sau dives plE ume, spieen/plaspao,ratneddsofnoe mpaosazsosiuapnlapsasrticvasctroonoesladne- The mean liver/plasma, spleen/plasma, and bone marrow/plasma carbon-14 i mack iely, 80 dave after + level ratios calculated from data reported fcr potassium perf_uorooctane- hots to cones to te Sigs catbo1ns salfenate (6) are 9.3, 0.2, and 0.2, respectively, at 89 days after a er hoor mcimmepiitonian Sieve |I single intravenous dose. Thus, in contrast to the tissue carbon-14 Eaves Fompotic siaman/pioves forts ;:. i ratio data from PC-E07, the perfluorooctanesulfonate-14C tissue/plasma ee a reine 1s shh fo oy 8 metas | ratio data are similar to the N-ethyl FOSE-14C tissue/plasma ratio if i if i or tio. separ there civeve/plasma totic data. Although perfluorooctanesulfonate is shown to be a metabolite TOE Ee retas as soldonee th the Soman 1d of N-ethyl FOSS (see below, this report), these tissue/plasma ratio re ei ares In sive 1 ave ony 55 similarities should not be interpreted as evidencec, that the carbon-14 labeled material at later times (32 days) in liver is due only to Be emesmsescttsre: perfluorooetanesulfonate. me RasE-Lite of the issppesrance fin plas of casbon-id from The LeSL aTeie after Gay hn assngpescance 18 meh Gay half-life of 1 to day 16 (tFhiegudriesa11)p)peiiassra77n..5c5eddaafyrysosm plasma of carbon-14 from aafftteerr NN--eetthhyyllrFoOsSEe--1c4C. re day 1 to day 16 (Figu en, ee LEE Sere one das 35 are sooo the owe administration. However, after day 16 the disappearance is much slower since the mean carbon-14 levels on day 32 are about the same as ares on a4my116.3 s caTvianEsnts aoo Sooy 16,7.2.d1e3v0e tox the meNr. levels on eay 16 (2.2 ug equivalents on day 16, 2.1 vg TT abniscration of potas ion Ceiqiubiovna-lie4ntsaafftctenerrcaNN-l-eett3hh2yy)ll. FTOheES-Ep1il4-CCasoomraraalhlaslafdd-mmliiinnfiiessttvrraaalttuiieoonnofiiss7t.th5heedassayammseefoaarss FOS c:bon-14 meee te may 10s (eseinated from do | 20 t;;at reported for carbon-14 after oral administration of potassium perfluorcx,ctenesuifonate-14C 0 ae See See of alsarseniance of sytbo4n fim day 6) (4). AAss wwiitthh NN--eetthhyyll tc male rats FFOOSSES--1144CC,, iitt (estimated from day 1 to iiss aappppaarreenntt tthhaatt ssoommeettiimmee day 6) (4). after a few days (>6 days) the rate of disappearance of carbon-14 f:cm BTL A ie 0 perbitoresctepeifonssVeE- sectesses plasma after administration of perfluorooctanesulfonate-14C decreases to a much lower rate. overE ati thE e pattearEnaoSnfhcoLrisvoenr-1F4oSidsvtseeibpnuosrikoenacsisTnstSsicpaatssesasentam3oee0,s otpfhnebion for Bethy) P0SE-14c and porseegum perfluorooctanesulfonatei=c!. Overall ,the pattern of carbon-14 distribution in tissue and the half-life values for the first few days post oral dosage are similar for N-ethyl FOSE-14C and potassium perfluorooctanesulfonate-1 dC. ne Ler Bios valve for casbne1d in addition, for both compounds-a, the rates of disappearance of nui va babe from che Saciier carbon,-14 seem to decrease so that later plasma values for carbon-14 oe. os tor hess compose 1 10s levels are somewhat higher than would be predicted from the earlier esters prediction of Flats sevels st Tove levels and thQ half-life values. Thus for these compounds in rats eo enter or wiiniiation from phoens ore (and likely other species), predictions of plasma levels at later tines based on half-life estimates of elimination from plasma are neere Ta a ee! inaccurate and should not be attempted. EE eo To oem somone, 2a nThee net cchhaannggee unique iinn to rraattee ooff N-ethyl eelliimmiinnaattiioonn ooff ttoottaall ccaarrbboonn--1144 ff--comm ppllaassmmaa FOSE-'4C and `perflourooroocotcatnaenscuoluflofnoantaet-e1s4CC;; iiss iitt nct unique to N-ethyl FOSE-14C and perflu is quite common for other compounds. PSSM COaNFrIDm ENe TIn AAL IRR WadeAvalbya3bflo Inspection and Copying as Confidental formation Made Available by 3M for Inspection and Copying as Confidential Information: SSuubbjjeecctt ttoo PPrrootteeccttiivvee OOrrddeerr IInn Pcaallmmeervrv.. 33MM,.NNoo. C22-00u40-6330059 28133..00009 - 3SMMA1A00S5H 3194 | . rage " Page 8 Jaotation and geneitication of Metabolites lites : ITIaashnttoeel4ieal6tttiisivhvhhoeeoenrsvuacireahtshcnohodmmaaiooffeIggitiandeeeeeernrnrnaa.tttaatieeh(fseBFiippircnmonFaaoogaictllllltieetio(eo(nr9oon3:rr:oa1a1c1f,l,l)orMdwvSeteoaoahtnstotaeeeeeubr/oo/oweftfielitxoNNshts-oszueeuosettece)hh)tiyyedflldfmrraoFotvFmOhnOiSeStrrrZShra--ot11(te(s4AeFnFCCrlrsaosaacwarvcctacoatrsrisfiiioooffenrneiixnxcc2--2ee))dd;; tracted with ether (Fraction 1) then with acid-ethe inet i raction 31. The pescunt of cordoned extracted trem after filtration, the filter cak; v, extracted with chloroformTo Toa: honcsanate for each fraction vas: Fesction 1, 30.181 methanol 1:1 (Fraction 3). The p~..;~nt of carbon-14 extracted from ever ar Ta ey and praction 3, 11.6%. The water layer sepurated homogenate for each fraction was: Fraction 1, 30.18; EtFbThrEyeaefcaelitirliEtvtoserncriraatt2keooi,enoni2ncvC5oeo.nbntb1tetee8afafni;ooitrrnnseeeeadndodtfthnhnFNeeoor-acdd11ctee:1t1httiyeeocsccenhttnlaaiFob3boOrl,lrSoeeoEf1t-oc1oa1ra.mrCm8rmb-8buom.ompnenerct-teiTh1hshda4aeennntao(Owll0Va8i)te)en.ex.xrtttrihlTaTeaahhccyetukfeeisia,ro,ocnenossoeofofpffpatotrtohthalhehet,eeed Tofilt 1052 vg eensqtuviavtaelnetnst.s (o6f70)N as -ethy extracted. l FOSE-14C xtracted. present in the feces, pool, 705 heThe TOrSand 3uo3ogreffserefqaceaucoccoitlktrviouinaoudmnlnnnnesessenttwwvwhseeeearrrr(eeeen6c7cceehh8hll-)-uuootr(mwmeeFaaaddltstuoospsgeguitrccceaaccppe5ehh1smeesssddiivvnoeeodnlnlyyssrevweeipipttatahhhrraaarctotielhelloossr@riiolollfufiioaoccrtraamneggeCe(G-)li4l.IicncaoaolttTlueehumemnAArs)s)e;; the eeroens14 remouea fren any of the EcloulautmensC)b.y sTehtehraercl 1:1 chloroform-methanol (Eluate B); and methanol ( O ee)Eox each of the diver horogenate extractions that vere was very little carbon-14 removed from any of the columns by methanol bes on a siiica gol colinn, thee are tvo Column eluates (Eluate C). For each of the liver homogenate extractions that were ee neatning carben-14. he selstive carbon-1d content of aphed on a silica gel celurr.n, there are two column eluates Dunes) mas Tor each traction see shom in Table 7. chronatogz (A and B) containing Carbon-14. The relative carbon-14 n are shown in Table 7. content of EThtoT lhheueianmt-sselie isxaxyeAcecoroallnuucndmmhtnnrheBoenfmrfafraecitoatanarcoccgtgtitseniirhaooaeacnpnFphshsrbyyaa.f(.sc(rEetBalilcuRoasPtaanaeaittdswdoeeiessiosrccosAAhecrhaosasnmnohyddaoantwtaB3one)t)gnroiiwawnnis(mmee1tFsFrr0iiee0gfgfrucuccrohrrhhomrleermoocssmrtetoaha3h3ftiti--oonon11rg-s2-2mr.ltl.,aaaappyyhheeWW3eerrh5eddennccnhehbbytyrrhooammnsac~-l, SR rotcaioc) (Figures 3.5), the thiee column eluates G's) tography of these six fractions ara hed in the same solvent shown system (100 chloroform, 35 methanol, chromatograp he three column eluates (B's) ra Three extractions. (eiher, cid-ether, 1:1 enloroform-rethanod) 5 amTon.ium hydroxide) (Figures 3-5), t Ete ome nagor peak, and comparison of the radiochromatostans the three extractions (ether, acid-ether, 1:1 chloreform-rnethanol) TfsFeE EEraruocagmhcgteL nishoatvnsep2tT3ieohtrn(atteeateancciemcidaaaas(ct-joo1hhtoee0urtt6achhcneoepoptrnenr.o)tat)taakasEini,yBselnnltlauuesnasttndtthh.eeee1c0(Bo5ss1amuaa8rpmvwc9sreaaaeeerssttcimmiihscececlcohttohnraatiasbobooceoomfoiimlfdoaldsi,rti,ttnottoe,ghep11.re.r00aa1prwpw0ThTaah0aehhtdetedeiedeerort)ce)eiihhxnxnartt(nGorraF+iomaaiglacscgsu,ttetueroicircgeoooeo3rnnnn1ad6ddm))s2 solvent system (10C butanol, 10 S210 acid) (Figure 7). Tne three fadiochiomatogcans of Fraction 2 and in a third solvent system (100 chloroform, 100 methanol, and 2 Ee TAT hat ine Fadioshestcal por ity of the metabolite is acetic acid) (Figure 7). The three radiochrcrnatograms of Fraction 2 Eluate B indicate that the radiochemical purity of the metabolite is %Ta hTwa 9haeE5es8.eelbxxaettbterrelaalneeccaysdtttiiXoomm1inene1ot-t2FeFa0nrbrb0ataoactlcStiitpLitteiaoeecovntnoFrFrnror2e2mao.teccoo((thtrraaeiicyycziooiednnffd.-oo-errIsItthha$T11ene5h9Ord0FreP)-)-sNsrIEFuMieRlbbRlsumeuuaiiaalttttnnteteeaseeeliB8ddyysseitii(et(ocssochhcSloo5ie.o.nnoprroPoPtotrafahfhttotoeeerhrhdmrncVV--eeaainmrrneeoiiottfaafhhnnaattnnhhooeell)) Ciktonate aniooan.meticive vas. identified as the pestisozooctanc- Central Analytical Laborat XL-100 and XL-200 spectrometers. The results are reported in Appendix 9; the metaoolite was identified as the perfluorooctanesulfonate anion. "yp i3M ECiiiinpinSzmorai,l MSMauadtdeieeAAcvvaaoiillPaabbrlleeoobcyye33MMOffroorrrIInn1ssppeesccattiiimooennrvaa.nnddWCChooppnyyioin.gngaaassaCC0oonnaffii0ddesennttiiadaalllnIfnformation: Subject to Protective Order In Dalrner v. 3M. No. C2-04-6309 22881133..00001100 3SMMAA1100005533119955 .. PosePaae 9 FaFGTreeroronomamaTctettehheepDpooesppoiteelocrrcca((eeEt6nr77ot4t%r))moo-ffasanendtdtthootetttanahhleleelccttaaooarrttnbbaadololnnt-c-ch1aa1e4rr4bbpooeeennxxr.--ttcr1r1ea4a4ncctttrreeeecddccooomfvvpfreeroororsmmeei.ddtttihfhofeernroalmnloifivtvteehhtrreehechbcsooooemlmlouuo-mm-nnss eitCTSSnlheh0uaa5at1Lnt:tet1e3aesitcnAhltbeylyeeeoatnrtsthohthTyfiih2non2Tk-re2eolmiFl8a-ooyymvmoLeeeafetr-trhtheit1t4cachh4chenheirodoolccuismaneaaaartntrboSdaoouobsgnnttro-laha11tonpep44rohheyypippiennedar(ru(rcl9drf3tei5ii5li%nvv8nu)uete)gorrorcioreiottsoaxomtcttopcctrcoaa4aa4tsnnn68caiettnhbhbsiieeooucoouulnsnreerfussssoaiottnnffiiadaaommtffaatntetttthee-aoeeerr1tfdds4leCeCaaos..ssssiinnggllee ciiifornateehicToaatsooqmreawphhayt cthreetstetrhethsaernus2l21.amount of perfiuoioustene: dose of N-ethyl FOSE- C is due to It is quite likely that due to loss during extraction and to loss during chromatography that the actual amount of perfluorooctane- sulfonate is somewhat hThheeemccthhcliaoorraoopfthoorrenmdccooellruuimmnnng geetrllheuuiasanttt-eelernasyetffrhrraoonmmeht2teh2hee8em.atttohhsrreeeaeepheeyxxttrriaancctttiihooennsffmrreaaccttsiiooolnnvssentvweecree i Linn Ihe hiorotom-rethancd. loates, comparison of the three colin cGhyrsotmeamtc(c1r0a0phcehdloruosfionrgmm,t,hi33n55-lmmaeeyttehharannocolhl,r,om5atsaomsgmsrooannpiihuuymm hihnyyddrrtoohxexiidsdeae)m)e((sFFoiilggvuuerrneetss 88--1100)).. system (100 chlorofor As with the chloroform-methanol eluates, comparison of the three column istiexrcascotgigeosntsF.ratchattiomnos1t (oofthetrh)e Eclaucabcoen1A4va1sb cthherosmamteosmtestpahbeodliitne.3 t most of the carbon-14 is the same metabolite. t : TesSThleeecusTooarentRadxetsrscSsaaoOutclvctvIegieneonTtsnttFssSsryoyatshschvtttaeeeinnnton((s1100v100s(tebebuntuthtaea(nrn1o)o0ll0,E,lcuh11aDl0otraeaoccAfeeottrwiimacc,saaccc1ihi0dr0d,o,mzea11tt00hoacwvnraaotatleper,hr)e)da(nidiFgnigu3uarree 1011) | a"nedtiicn seid) Fiore 1210 a third solvent system ure 12). x100 chloroform, 100 methanol, and 2 mTaThceeeetieetcxxttirrataaceiccdttF)iiroonan(cFFtTirirgaoacncttii1oo7nnan11 d((epetuthhbeesrri))ttEeEldluuattsoetSAo.A Preiyeiointte FLroatcotriauooncyIIfoarnd rs-ubiminttesdnsityoeSis. PP(o(aacnetthhhhltlrrohoerereooffooVofoferrcsmtti))hhaeenvwCaCaXseesinnnttl1lrr0aa0baabelelllaeenddd I e mAXmeLne-tat2alab0bye oo0tlliSiecptacLieelte rectLttwearaeaboscomrteEttateeietenrlnortCsersai,ty.taiirfvviToTeeohrhllenyey14rrriiFeeedo-ressenNtuntMiltpRttiaissfrfaiifneeaiaaddurtloeeyra8ossrsoieecsppppeeoeoarorrrrnniteleleeusvtddocohrireioitrcno.ooVcncAAtaaatpprtnappieeneeas,ennnusddluiiXfiixxLott-ro.193cna.C.a.a0n-nniTTabidhnhededeee.. Similar to the calculation for eriemestStratTeenoertes321dosofe estimated that at least 328 of ptiofneheerfNcolceauatorrhrbbyooolonncc-t1F14aO4nSeEpps-rr1uee1lssCfeeonnnttiastiimenn,eldciiiavvtoeelrcriatnaoettbe4488 Fhroaucrtsioafntetrh. a single oral dose of N-ethyl FOSE-14C is metabolite FFFrFSruueoarrsmcttEuethhltieestorrnainnnrraIete'Iffa.iitmhnhneieiegmgmnehepeneenrtrttaooebeffsostltiiittvmnhheaaeetstseeeeteeooenfxfxtttatrrtthhaaieeccvtteilippoyoeanrnrsccsieednnaaetntnnoddatggiessefeeiFpoeoaaffdrraappstteesiisrooffpnnilesusuroofrrwwicooououuoolclcrddtotaoanlcnLeitieskikssneeuielll--yy- fsstEouieilnnmfacr oteanenatitmahtnieat ddseceetowheWiteiscittihhmignemustarrstateetebssesoppseleiciceeetttossett,aattbtobollefiinttoosthhrhhaeetthtitttevoohhtaetaatlatrlylettfcchhiiaeaednrreebbnmttootewwnoinno-ft-1mi1mee4eodtftaappbarbrtoeeoshslesleieipntnteeteterx.s.sftlrauaaBHrrocooeertvwoieeooppvvnrcreeetersrasasen,enndentt- a scia enhpraso-umrn baastittoioagornrnetanimimisasesalt(nnFqoFoiutaitgagtunupprtlrheianeostonsnitneee88dsd-e-.,1.x10t0)fr)TuTarhhacatnenehddheepbprrltrteheheeserseeebnfny33cic33ene%0tehoomooefffefsnetcotttthchehheooeefnrrdccitaatphrprieebeboaoaonkenknssx-set1dr4iiiannnciidtnrnriiaacottdatnhiihteoeeo-nanltsdiheavterr Crner unident LESed metabolites are present. homogenate that was not extractable by these metabolites are present. conditions indicate that other unidentified 3M CONFIDENTIAL SMMaaeddeecAAvvalaoiillPaarbbollreeeocbiyyv33eMMOrffdoorrerIInnnssppeeSccattiimoonneaavrnn.dd3CC.ooppNyyioingn6g2aa.ss04CCoo.nn6ff3ii0dde5ennttiaall IInnffoorrmmaattiioonn: Subject to Protective Order In calmer v. 3M, No. C2-04-6309 22881133..00001111 3SMMAa1I0n05I3s1I9R6 : Page 10 Page 10 Reterences References 1+ I. PJJOooShhZna-sIonAn,E, JImDDepaaannrddtsBB,eehherB,,ecFeFmEE:v:erSSyy1nnstthhee1ss3iiss8 and and Cherscterization Characterization of of N-Ethyl N-Ethyl 2. 2. TTTFTarrhhOaooaScmmcEkpspt-ss1oooo4nffnC,,t(tRhKReCCeepaaRonanrtddt)HbH,yoolDllelIicineesg,mh,beOOesLeLr:d:1R1oI,Isrrhr1cea9and8tii0aoa.tnticiiooonnh.ooff tathh3ee GGaayssettirrooeiiLnntteessesettriinnaall the Rat by Ingested Ruthenium-106. Am J Physiol 194, 3. 3. JJO3oro0hah8lnn-ss3ono1nen2,s,,e.J310D9(::5h8e.pAAobrbtssyoo,rrpputiitooynn oo1ff0, FFCC1--5887500,77--1144C in in Rats Rats After After a Single Single 4. 4. JOOJroorahhalnnlssooDDnono,n,seeJ30D((::RreeppAoNosbbresst)oo),rs,ppJGttuiirlooanyninoo1sff0,FC26C1-,-93975591--9.117454.CC in in Rats Rats After After a a single Single | 5. 5. SGJOcaorhahanlnlssoDDonoons,s,ee.J90D((1:RheappAAoorbbrtsstyoo),rr,ppOtDtciieotocnonebseoomrffrFF2CC63-8-,,114413931-79-1719544..CC in in Rate Rats Meter After a a Single Single 6. 6. FoJOoJofoofr-hha3TnTnl5soosottoDnHaano,l,lseeCCJIDaD(ar:r:RerbepopsoEnEorox-xrtt1t1tn)4ee4),nn,titiDDnneeaacRcRnneaeaddmttmbebsRReeoorAAruuffttste22ee8e8,roro,ff181EE99x7xS70cci9,rro.geeitteiioonnToaamnnrddavTTeiinssmsseuueeDoDbniinssttreoiihbbuuttiioonn a Single Intravenous Dose of 7. 7. AHMFA(laaCltcrt-rmyym9alila5nian-,nmn,1d4d,ePC1,LFF(eaaRdnneeddproaDortiitist)ost,nmmcDereor,fc,eADmDs5Sb:ee:criBoB2lol8oon,onddS19Oa7aEnn9Tdd.TIOOettShheerrToBrBooFedyyieFPrliusaiiaddmssi,.al BBeBeittnhhteeasscddyaa,,, ederation of American Societies for Experimental Biology, 1971, p.5. 33MM CC0ONNFFI"BDEE-- -N-T7I1AL'5 SMMuaabddjeeecAAtvvataoiillPaarbbollteeecobtyyiv33eMMOrffodorrerIInnIssnppeePccattiiioomnneaavrnn.dd3CMC,ooppyNyoii.nnggC2aa-ss0CC4oo-nn6ff3iidd0ee9nnttiiaall IInnffoorrmmaattiioonn: Subject to Protective Order In Palmer v. 3M; No. C2-04-6309 22881133..00001122 33MMAA1T00005533119977 Page 11 List of Tables, Figures, and Appendices Table 1: Et OCOruramalullDaDotoisseveeooEffxNcNr--eEEtttihhoyynll. FoPUfOSSTEEo--t14a4CCl CiiannrFFbeeoeend-d14toiRRnaaFttessce(sMeAafnteDrosea,n to (Mean Dose, 90.13 mg/kg) i Table 2: Table 3: Table 4: Cumulative Excretion of Total Carbon-14 in Urine After an Oral Dose of N-Ethyl FOSE-14C in Feed to Rats (Meen Dose, 10.13 mg/kg) ERE Cumulative Excretion of Total Carbon-14 in Urine and Feces After an Oral Dose of N-Ethyl FOSE-14C in Feed to Rats (Mean Dose, 10.13 mg/kg) EET Carbon-14 Content in Digestive Tract (plus contents) and Feces After an Oral Dose of N-Ethyl FOSE-14C in Feed to Rats (Mean Dose, 10.13 mg/kg) at 24 and 48 Hours Postdose Table 5: Carbon-14 Content in Tissues After an Oral Dose of N-Ethyl MSE-t 4C in Feed to Rats (Mean Dose, 1C.13 mg/lg) Table 6: Carbon-14 Content in Tissues After an Oral Pose of N-Ethyl FOSE-14C in Feed to Rats (Mean Dose, 10.13 mg'kg) Table 7: Relative Carbon-14 Content Qf Eluates A and B for Extraction Fractions 1, 2, and 3 Vigure 1: Mean Log Carbon-14 Levels (Normali2ed to a 10 mg/kg Dose) in Liver and Plasma of Rats (Groups of 3) at 1, 2, 1, 8, 16, and 32 Days Post Oral Dose of N-Ethyl FOSE-14C in Feed NB-53102-43-44, NB-56531-5 Figure 2: Ratio of Carbon-14 Level in Liver/Carbon-14 Level in Plamia of Rats (Groups of 3) at 1, 2, 4, 8, 16, and 32 Days Post Oral Dose of N-Ethyl FOSE-14C in Feed 10-531C2-43-44, NB-56531-5 Figure 3: Thin-L-ver Radiochromatogram of Extraction Fraction 1 (ether) Eluate B (1:1 chloroform-methanol) NB-51579-36 Figure 4: Thin-Layer Radiochrcmatogram of Extraction Fraction 2 (acid-ether) Eluate B (1:1 chloroform-methanol) NB-51579-36 Figure 5: Thin-Layer Radiochromatogram of Extraction Fraction 3 (1:1 S ETr L -- chloroform-methanol) Eluate B (1:1 chloroform-methanol) 1M-51579-36 Figure 6: Thin-Layer Radiochromatogram of Extraction Fraction 2 (acid-ether) Eluate B (1:1 chloroform-methanol) NB-51579-35 33MM CCOONNFFIIDDEENTMI"LAL Made Available by 3M for Inspection and Copying as Confidential Information: S`Suubbjjeecctt ttoo PPrrootteeccttiivvee OOrrddeerr IInn PPaallmmeervrv.. 33MM,; NNoo.. CC22--0044--66330099 28133..00013 3MA10053198 rose 12 Page 12 Lict of Tables, Figures, and Appendices (Con't) List of Tables, Figures, and Appendices (Con't) Figure 7: Figure 7: TTFhhliionn-seLitaa3eyyeesr(1RR11aaddiSiohoccihhoreroaommfasottroomgsremaeemcmhaoonffolEE)xxttrraacNcett-ii5oo1nn57FF9rr-aa3cc5ttiioonn 2 2 (acid-ether) (acid-ether) Eluate B (1:1 chloroform-methanol) NB-51579-35 Figure 8: Figure 8: TFThhliionn--sLLtaaaeyy"eerrenRRtaaoddrioooctchohrrramom)maattooMgg-erssa1mm57oo5ff-3EEx6xttrraaccttiioonn Fraction Fraction 11 (esher) (ether) Eluate A (chloroform) NB-51579-36 Figure 3: Figure 9: TlThhoiinnr--eLLaasyyeerrXeRRhaaoddirioooccthhorrroommmaattooggNreoaacmmas7oofaf-E3Ex6xttrraaccttiioonn Fraction Fraction 2 2 lsckd-ethes) (acid-ether) Eluate A (chloroform) NB-51579-36 Figure Figure 10: 10: TThhhliiornc--cLLtaatyyaee-:rrReRatadhsiatonoccchthr)aommaaEttaooggveresamsAsooff(mEEixxctttreoasrccottriinoo)nn |FFrrNaoBcc-t3ti1iSoo7nn93:33((11:111 i chloroform-methanol) Eluate A (chloroform) NB-51579-36 Figure Figure 11: 11: TBThhliiunn-neLLtaayyeerr(oRRmaaiddoiiroooctchohrrimcc)vmaa|ttooMgoirr-sa5mm157oof5f-E3Bx5ettrzaaccttiioonn Fraction Fraction 1 1 (ether) (ether) Eluate A (chloroform) NB-51579-35 Figure Figure 12: 12: TFThhliionns--tLLeaayyeerr(eRRnasoddriioootccohhrrrnaa)nsasttooggRrr-aa5sm157oo9ff-E3Ex5xttrraaccttiioonn Fraction Fraction | 1 (ether) (ether) Eluate A (chloroform) NB-51579-35 Appendix 1-Table 1: Appendix 1-Table 1: Appendix 1-figure 1s Appendix 1-Figure 1: Mopendix 1-rigsse 2: Appendix 1-Figure 2: Jopendix 1-Figste 3: Appendix 1-Figure 3: Appendix 1-Pigure 4 Appendix 1-Figure 4: Appendix 1-Figuce 5: Appendix 1-Figure 5: rovenatx 2: Appendix 2: Appendix 2-Tabie 1: Appendix 2-Table 1: repent 3: Appendix 3: FTThhoiisnnt--LitaaiyeyeerraCChhsrrooemmaanttooetgsitraapphhyy Systess Systems for for N-EEhyL N-Ethyl FOSE-14C 10-51806-41 TTShhoiitnni-n-LgLaayySeeartrusRRiaaoddnii,oocchhPrrioasmmcaaettoohogs.reaams1 ooffWBNN---5EE1et8hh0yy6l-l4F2FOOSSEE--11d4Ce Dosing Solution, Plate No. 1 NB-51806-42 TTShhoiirnni-n-LgLaayySeeorlrutRRiaaoddnii,oocchhPrrioasmmcaoettoanogg.reaemn7 ooffNBNN---5EE1tt8hh0yy6ll-4P2POOSSEE--1i4cC Dosing Solution, Plate No. 2 NB-51806-42 TTDhhaitinim-niLgaayySeeerrlutRRiaaoddnii,oocchhPrrioesmmcaaettoonogg.reaemn3 ooffW-NN5--1EE8tt0hh6yy-ll4F2FOOSSEE--1i4cC Dosing Solution, Plate No. 3 NB-51806-42 TTShhaiisnni-n-LgLaayySeeertratRRiaaoddnii,oocchhPrricasmmtaaettooNgeo,reasmm4 ooffNBNN---5EE1te0hh0yy6)l-4F2FOOSsSE--l1i4Cc Dosing Solution, Plate No. 4 NB-51806-42 TTShhoiianni-n-Lgiaayy`SeeerrksRRtaaiddoini,oocchhPreiooemmcaaettoohgog.reaamn5 ooffNDNN-=-3EE1tt0hh0yy6ll-4FF2OOSSEE--t1i4cC Dosing Solution, Plate No. 5 NB-51806-42 Determination of Casbon-14 Content of N-Ethyl FD7eOOtSSeEEr--m114i4CCnaDDtooissoeen//oFFeefeeCdda!rMfbiioxxtntu-ur1re4e Content of N-Ethyl CCwaaisxrbeboaonrnee-11d4 Content Content of of NEEL N-Ethyl FOSE-IAC FOSE-14C nose/Teed Dose/Feed Mixture RDRaaottseHW/eeFiieggchhdttsMsixaatinuderAAemmooAudunnnittnoiosfftNNe--rEBettdhhyytllo PEFOa0ScShEE--RT1ad4Ctc Dose/Feed Mixture Administered to Each Rat } i 1. 3WNM onprFieEeTe=IinLg `i MMaaddee AAvvaaiillaabbllee obyy 33MM ffoorr IInnssppeeccttiioonn aanndd CCooppyyiinngg aass CCoonnffiiddeennttiiaall IInnffoorrmmaattiioonn: S`Suubbjjeecctt ttoo PPrrootteeccttiivvee OOrrddeerr IInn PPaallmmeervrv.. 33MM,, NNoo.. CC22--0044--66330099 2881133..00014 3MA10053199 3MA10053199 rane 13 Page 13 ---- List of Tables, Figures, and Appendices (Con't) nrpentin 4 Appendix 4: Appendix A-taste is Appendix 4-Table 1: Appendix A-table 2: Appendix 4-Table 2: Setecnination of Recovery of Tota: Cazbor-1d Determination of Recovery of Total Carbon-14 Free Bion Bletosient Suipies Spiked Rich ReEEhYL From Blank Biological Samples Spiked With N-Ethyl re POSE-14C Recovery of Total Casban:id Prom Bark ioloical Recovery of Total Carbon-14 From Blank Biological ee pia aati Foret, comtoetion Samples Spiked With N-Ethyl FOSE-14C, Combustion pit Set No. 1 Recovery of Total Carbens1d From Blak Biological Recovery of Total Carbon-14 From Blank Biological eseer plas hn eat FomEi-eT comurtion Samples Spiked With N-Ethyl FOSE-14C, Combustion Appendix A-tabte 3: Rp ecoverys of TotaH l CacbE ons14rFeicx Blanpeiaaalatsitoenal Appendix 4-Table 3: Set No. 2 Recovery of Total Carbon-14 From Blank Biological Samples Spiked With N-Ethyl FCSE-14C, Combustion appendix A<tanle 4 Appendix 4-Table 4: Appenix Scpable 11 Appendix "able 1: Set No. 3 Recovery of Total Gasbon-14 Pron Blan Diclasical SRaemcpolveesrySpoifkeTdotWailtthChaNrN-bEEottnhh-yy1ll4 From Blank Biological FFCCSSEE--'144CC,, CCoommbbuussttiioonn Samples Spiked Wi - red Set No. 4 Tokai Carbon-14 in Feces Attar in Oral Dose of Total Carbon-14 in Feces After an Oral Dose of EWonseTes Ta reas to mite ean sores N-Ethyl FOSE-14C in Feed to Rats (Mean Dose, Appenix Sctsste 7: Appendix 5-Table 2: f-- Appendix 6: Nope 70 Appendix 7: Appendix T-tasie 11 Appendix 7-Table 1: f-- Appendix 8: 10.13 mg/kg) Tocal Carboni fn rine Aes an Ocal Dore of Total Carbon-14 in Urine After an Oral Dose of rr rete to hee mean pes N-Ethyl FOSE-14C in Feed to Rats (Mean Dose, pte 10.13 mg/kg) Carton Content in Digestive race (as contents) Carbon-14 Content in Digestive Tract (plus contents) CoE Bares Neuen a ora Bose st hoptiyd FOSELTIE and Feces After an Oral Dose of N-Ethyl FOSS-14C Dstt ere eis em in Feed to Rats (10.13 mg/kg) competative Date Shaving Norsal Fecal Excretion for Comparative Data Showing Normal Fecal Excretion for wRats Comparative Dota Showing Noresl Fecal Brereton for Comparative Data Showing Normal Fecal Excretion for foreRZts Carbon-14 Contens in Tissues Atte: mn Ocal Dose Carbon-14 Content in Tissues After an Oral Dose BHee ns Paste in Peo so acs ean Domes of N-Ethyl FOSE-/4C in Feed to Rats (Mean Dose, appendix 3: Appendix 9,. Reporrt.eoftGearTreacMtiiyoeniTcaannaTa1bosasosy Mnaiyaie 10.13 mg/kg) Report of Central Analytical Laboratory Analysis of Metabolite Fractions I and II 3 Clarina Made Avaiable oy3 for Inspacton ana Copying as Confidentigal Information Made Available by 3M for Inspection and Copying as Confidential Information: SSuubbjjeecctt ttoo PPrrootteeccttiivvee OOrrddeerr IInn PPaallmmeervrv.. 33MM,, NNoo.. CC22--0044--66330099 28133..00015 ~-- I aMA10053200 3MA10053200 Page 14 oeTable 1 Cumulative Zxcretion of Total Carbon-14 in Feces After an Oral Dose of N-Ethyl FOSE-14C in Feed to Rats (Mean Dose, 10.13 mg/kg) Collection Period (Days) Rat Identification A B c Mean + S.D. 1 Day Group 0-1 29.98a 12.41 22.55 21.65 + 8.82 if 2 Day Group 0-1 18.99 15.60 11.80 15.46 + 3.60 1-2 34.73 28.98 20.59 28.10 + 7.11 4 Day Group 0-1 7.74 5.27 9.53 7.51 + 2.14 1-2 14.04 12.32 16.89 14.42 + 2.31 2-3 20.03 17.78 21.74 19.85 + 1.99 3-4 23.56 22.48 26.08 24.04 + 1.85 8 Day Group 0-1 2.36 7.71 4.31 4.79 + 2.71 1-2 5.61 27.16 12.70 15.16 + 10.98 2-3 25.77 38.21 20.32 28.10 + 9.17 3-4 37.41 44.41 26.15 35.99 + 9.21 4-5 42.83 49.21 29.27 40.44 + 10.18 5-6 47.14 52.55 32.52 44.07 + 10.36 6-7 50.65 54.86 35.83 47.11 + 10.00 7-8 53.36 56.35 38.77 49.49 + 9.41 0-16 66.27 16 Day Group 60.39 62.79 63.15 + 2.96 0-16 16-32 63.86 66.73 32 Day Groff 47.62 56.93 56.72 - 56.07 + 8.15 59.36 61.01 + 5.10 a Data are expressed as percent of dose excreted during collection period. Notebook Reference: NB-55673-37 and 38 3aM0 cCcOrN~iFnseEa_TT--~~tIias Made Available by 3M for Inspection and Copying as Confidential Information: S`Suubbjjeecctt ttoo PPrrootteeccttiivvee OOrrddeerr IInn PPaallmmeervrv.. 33MM,, NNoo.. CC22--0044--66330099 2881133..00016 3MA10053201 Page 15 Table 2 Cumulative Excretion of Total Carbon-14 in Urine After an Oral Dose of N-Ethyl FOSE-14C in Feed to Rats (Mean Dose, 10.13 mg/kg) Collection Period (Days) Rat Identification A B C Mean + S.D. 1 Day Group 0-1 0.131; 0.12 0.11 0.12 + 0.01 2 Day Group 0-1 0.14 0.09 0.11 0.11 + 0.03 1-2 0.23 0.17 0.20 0.20 + 0.03 4 Day Group 0-1 0.11 0.10 0.11 0.11 + 0.01 1-2 0.25 0.24 0.22 0.24 + 0.02 2-3 0.36 0.34 0.33 0.34 + 0.02 3-4 0.50 0.44 0.43 0.46 + 0.04 8 Day Group 0-1 0.10 0.06 0.09 0.08 + 0.02 1-2 0.17 0.18 0.21 0.19 + 0.02 2-3 0.30 0.28 0.34 0.31 + 0.03 3-4 0.62 0.36 0.44 0.47 + 0.13 4-5 0.88 0.61 0.53 0.67 + 0.18 5-6 0.97 0.67 0.61 0.75 + 0.19 6-7 1.06 0.72 0.71 0.83 + 0.20 7-8 1.12 0.77 0.81 0.90 + 0.19 0-16 2.45 16 Day Group 1.19 1.10 1.50 + 0.75 0-32 1.85 32 Day Group 2.69 1.62 2.05 + 0.56 a DDaattea aarree eexxpprreesssceedd aags ppeerrcceenntt ooff ddoossee eexxccrreetteedd dduurriinngg Ee collection period. vem sete, sri Notebook Reference: NB-55673-38 ii M3t:una4 00MCONFIDENTIAL Made Available by 3M for Inspection and Copying as Confidential Information: SSuubbjjeecctt ttoo PPrrootteeccttiivvee OOrrddeerr IInn PPaallmmeervrv.. 33MM,, NNoo.. CC22--0044--66330099 28133..00017 3MA10053202 base 16 4tl Page 16 Table 3 Table 3 in Urine CCauunndmuutFlaeactteiisvveeAfEEtxxeccrrreettainioonOnraoolff TTDoootstaealloCCfaarNrbb-ooBnnt--m11)d4 FosE-Te in Urine ainndrFeceacestoAfRtaetre (ean Dose, 10.13 m/ks) an Oral Dose of N-Ethyl FOSE-14C Dose. 10.13 mg/kg) in Feed to Rats (Mean csoCenrotiloolseccttiGiaooynne) Period (Days) x Bat Rat ItdaeennE ttiisfiiccaattiioonn T A 8 C wemsso Mean S.D. 1 boy Grose. 1 Day Group 0-1 8 Ts mes 27a ne | 0-1 30.11a 12.53 22.66 21.77 - X1.82 2 oay Grow 2 Day Group ot 1.13 es Hor asses 361 0-1 19.13 15.69 11.91 15.58 + 3.61 2 alse as nl wi 2 1-2 34.96 29.15 20.79 28.30 + 7.12 oay crap 4 Day Group ;i 0 7.05 t57 set ners 21 0-1 7.85 5.37 9.64 7.62 + 2.14 2 12s 1256 mess 230 1-2 14.29 12.56 17.11 14.65 + 2.30 3 20139 wz lor lex ise 2-3 20.39 13.12 22.07 20.19 + 1.98 Wes mm 5 20.50% 1.85 3-4 24.06 22.92 26.51 24.50 + 1.83 ot 2.06 & oryTGorou Go esse 2.68 0-1 2 She ain mien isla E1009 1-2 23 wor 6s 06 mE si 2-3 34 wo am 25 646k Sis 3-4 ws om sla len an Eo 4-5 se wn sz Bn awe: oi 5-6 oo sin 55.58 ise 47.6% 0iae 6-7 = We ose BE sos: se 7-8 2.46 5.78 26.07 38.03 43.71 48.11 51.71 54.48 8 Day Group 7.77 27.34 38.49 44.77 49.82 53.22 55.58 57.12 4.40 12.91 20.66 26.59 29.80 33.13 36.54 39.58 4.88 T 2.69 15.34 + 10.98 28.41 + 9.14 36.46 + 9.19 41.11 + 10.26 44.82 + 10.44 47.94 + 10.36 50.39 + 9.46 ois 2 Tere fe wma one 0-16 oz Go.se 22 basyeeorrewp. 0.98 2.06 2 4.83 0-32 68.72 68.58 16 Day Group 61.58 32 Day Group 59.62 63.89 64.73 + 3.64 60.98 63.06 + 4.83 A DDcoaottlaalecaatcreieoneexxppprreereisscssdee.dd as as percent percent of of doce dose excreted excreted uring during collection period. Notetook Refesence: NB-S5673-3339 and and 40 40 ' -55673- Notebook Reference: NS 3M CONFIDENTIAL MSMuaabddjeeecAAtvvaatoiillPaarbbollteeecbbtyyiv33eMMOrffodorrerIInnIssnppeePccattliioomnneaarvnn.dd3CCM,ooppyyNoii.nngg2a-ass04CC-oonn6ff3ii0ddee9nnttiiLaall IInnffoorrmmaattiioonn:: Subject to Protective Order In Palmer v. 3M, No. C2-04-6309 22881133..00001188 33MMAA11000055332200:3 . PPaaggee 1177 Taste Table 4 CCaarrnbbdoonn--F1e14c4esCCoonnAttfeteennrtt ainnn DODriieggleessttDiiovvseee TToerfaaccNt-tEt((hppyllluussFcOcoSonnEtt-e1en4ntCtss)) and FiIenncFeFeseeedAtfatttteoor2R4RaaanttasnsOar((aM4Mle8eaaDnnHooDusDoreossseoe,fP,oNs11-t00Ed..to11hs33yelamg/F/OkkSg)F).-14C at 24 and 48 Hours Postdose IdentRRiaaftitcation Identification DTToiisnmsee oPpsoosrstts--) Dose (Hours) DD(iipagieeusnttiicvvoeentTeTnrrtaascc)tt (plus contents) Feces Feces n1A " " ~- 1B 1C Mean 4+5.0. Mean S.D. x 2.08 29.98 24 12.84a 29.95 2 2.40 122..4411 24 22.40 2 14.60 22.55 22.55 24 14.60 16.6145.00 20.2+ 688..58822 .65 16.61 + 5.09 21 22A =2B 2C Mean ++5S..0D.. Mean, no 11.10 wm 34.73 48 13.03 2280..9988 13.03 48 4"8 1100..1100 2200..5509 Mars+ nas 204+0770.011 28.10 11.41 1.49 2a Data sre exprreesssseedd aoss ppeerrcceenntt ooff ddoossee.. exF Date are Notebook Referreennccee:: NB--5511880C66--4499--5511 NB Notebook Refe L CONFIDENTIAL MSMuaabddjeeecAAtvvataoiillPaarbbollteeecbbtyyiv33eMMOrffdoorrerIInnIssnppeePccattliioomnneaavrnn.dd3CCM,ooppyNyoii.nnggC2aa-ss0CC4oo-nn6ff3iidd0ee9nnttiiaall IInnffoorrmmaattiioonn:: Subject to Protective Order In calmer v. 3M. No. C2-04-6309 22881133..00001199 -------J 33MMAA1100005533220044 Page 18 onlin Rat Identification ?able 5 RT re ET Carbon-14 Content in Tissues After on Oral Dose of N-Ethyl POSE-11L in Peed to Rate 04ean Dose, 10.13 egAg) ont vt ime Liver! Spleen Kidneys sop "UE Lungs! Red Blogd Cells- naTEEE.E plasmas Digestive React cntsn caressse 1A 1B 1C Mean 16.85 17.98 16.95 17.26 0.16 0.13 0.11 0.13 0.71 1.12 0.80 0.88 C.43 0.60 0.39 0.47 6.39 6.80 7.82 7.00 2.55 3.10 2.80 2.82 12.84 22.40 14.60 16.61 18.16 23.48 17.40 19.88 2A 2B 2C Mean 17.72 18.23 _ 24.17 20.04 0.14 0.10 0.16 0.13 Poamofn 4A 2.1.59 0.14 49 18.47 0.12 4C 17.69 0.13 Mean 19.25 0.13 0.66 0.77 1.00 0.81 0.35 0.40 0.59 0.45 mow 0.77 0.98 0.75 0.43 0.43 0.38 0.83 0.41 5.99 5.77 3.62 2.06 2.17 ;.32 5.09 2.52 ouow 5.44 S.85 5.74 2.67 2.96 2.72 5.68 2.78 . 11.10 13.03 10.10 11.41 oc d 12.3r 15.62 19.29 15.74 d 8A 8B 6C Mean 15.44 12.83 18.30 15.52 0.04 C.C4 0.09 0.06 0.32 0.27 0.54 0.38 0.16 0.14 0.36 0.22 2.78 2.37 3.84 3.00 1.15 1.19 2.05 1.46 16A 16B 16C Mean 9.52 12.10 10.32 10.65 0.02 0.02 Lr.03 0.02 Eom 32A 7.84 O.C2 328 12.71 0.03 32C 8.04 0.01 Mean 9.53 0.02 0.18 0.16 0.27 0.20 om0.18 0.31 0.16 0.22 0.09 0.09 0.14 0.11 0.77 0.99 1.08 0.95 owmow 0.07 0.13 0.07 0.28 0.87 0.30 0.09 0.48 0.72 0.85 1.16 0.91 ow0.78 1.13 0.64 0.85 oc oc I Date are expreseed as percent of dose in tissue. b Data ate estimates of percent of dose present in red blood calls. Red blood co'1 volume ntem 26.3 ml/kq body weight (7). c Data are estimates of percent of dose present in plasma. plasma volume - 31.3 el/kq body weight (7). o 22 Ee cen d Sample was not taken. Notebook References! NB-56531-8 and 9, NB-51806-49, and NB-53102-49 A 3M CCOONNFFIIDDEERNTTIIAALL adoAvaablooy for Inspecton and Copyingas Confident informatie Made Available by 3M for Inspection and Copying as Confidential Information: S`Suubbjjeecctt ttoo PPrrootteeccttiivvee OOrrddeerr IInn PPaallmmeervrv.. 33MM,, NNoo.. CC22--0044--66330099 22881133..00002200 aw10053205 3MA10053205 ra0~ Sv TETRA SAE Table 6 Carbon-14 Portent in Tissues After an Oral Dose of N-Ethyl POSE-14C in Peed to Rats (Mean Dose, 10.13 ag/kg) Rat Identification Livery Spleeny Red Blood Bone Digestive Subcut. Abdcn. Kidneya-a Lun! ges Celle! Plasma&- Marrow Tract& Caressa' Tat! Pat!- Muscle' 1A 32.4 18 48.7 1C 30.4 Mean 37.2 BoM 2A 30.4 28 41.8 2C 41.4 Mean 37.9 4A 4B 4C Mean 43.1 43.8 39.2 42.0 6.72 6.88 6.06 8.87 14.39 8.54 6.55 10.60 WOM 5.76 4.68 7.26 6.70 8.00 10.44 5.90 8.38 6.07 11.66 7.76 9.18 om6.21 6.57 6.76 7.18 21.80 27.24 . 25.61 7.31 10.42 7.74 24.91 8.49 oER ud 16.83 20.10 12.25 5.53 6.36 9.46 i1.06 7.12 6.55 7.41 6.65 6.87 8.56 10.98 9.54 9.69 8.06 8.83 7.59 8.16 18.28 20.86 19.34 19.49 7.53 8.84 7.69 6.02 12.31 14.73 11.02 11.77 31.41 10.78 2.27 3.17 2.03 6.40 7.70 4.92 8.04 9.51 6.15 D.40 0.42 0.34 12.09 17.99 2.49 6.37 7.90 0.39 Ea WEES 10.42 10.59 11.35 8.27 12.03 6.04 1.43 1.93 2.39 3.96 4.18 3.95 3.26 3.99 4.20 0.22 0.37 0.52 10.79 9.46 1.92 4.03 3.84 0.37 7.97 b b 2.15 2.06 1.58 9.80 2.99 1.75 1.36 8.67 1.82 1.74 1.32 8.81 2.32 1.86 1.42 8A 99 8C Mean 26.1 24.0 33.6 27.9 2.09 1.75 3.87 2.57 3.25 3.35 6.16 4.25 2.79 2.55 6.34 3.89 8.19 7.46 12.27 9.31 2.85 3.15 5.5D 3.83 3.27 2.83 - 5.48 - 3.86 - - 0.53 0.37 - 0.98 0.22 0.69 0.47 - .0.73 0.35 0.33 0.24 0.9S 0.51 16A 168 16C Mean 20.4 27.9 26.3 24.9 0.81 0.84 1.08 0.91 1.86 1.99 2.98 2.28 1.43 1.76 2.29 1.83 2.18 2.95 3.16 2.76 1.70 2.1.3 2.64 2.22 0.96 0.98 1.48 1.14 - 0.03 0.04 0.16 0.13 0.01 0.16 0.35 0.03 0.20 - 0.17 0.03 0.17 32A 19.7 0.74 1.81 1.61 D.81 1.89 0.67 -- - 32B 32.8 1.33 3.47 2.38 2.58 2.19 1.46 - - 32C 20.4 0.62 1.75 1.32 0.86' 1.54 0.61 -- - Fy pp ------ Mean .24.3 0.9C 2.34 1.77 1.42 2.07 0.91 a Data is normalised to a 10 mg/k9 dos* and expressed as ug R-ethyl !OSE-14C equivalents/0. b Sample was not taken. Notebook References: NB-56531-5 and 6, 103-53102-43 and 44 0.08 0.28 0.06 0.14 0.DO O.DO 0.00 0.00 0.13 0.28 0.09 0.17 33MM CCOONNFFIIDDEENNTTIIAALL Wade Avaalo oy for nspacton ancCopying a Cadet formation Made Available by 3M for Inspection and Copying as Confidential Information: S`Suubbjjeecctt ttoo PPrrootteeccttiivvee OOrrddeerr IInn PPaallmmeervrv.. 33MM,, NNoo.. CC22--0044--66330099 2881133..00002211 awao0saz06 3MA10053206  | | PPaaggee 2200 Tabte Table 77 RReellsattiifvvoere CCEaaxcrtbbroaoncn-t-1i14o4nCCooFnrntatecentntitonoosff EE1ll, uusa2tteeessndAA3aanndd 3B for Extraction Fractions 1, 2 and 3 FFrr(aaaccttthiioeon)n. 1 1 (FFarrcaaiccdtt-ieitoohnner22) (131 chFlFroraracoctftioioronmn-n33ethanol) nol) ----------(-- ethe--r) ----(-- acid---eth--er)----(1:-- 1 ch--loro--for-- m-me--tha---- Eivate A a93% 3238 6o1n8 tnEllouratoetoAm) i (`hloroform) slate 8B 119508 6B1a8 222208 ((111:m11Eeltcuehhhaaltlnoecorrloo)ffoorrnm-- _ -- methanol) otal 4 1n1a2e8 3842 88338 Total. 8 -recovered NNootteebbooookk RReeffeerreennccee:: NNBB--S511557799--3344 ~~tpEgt~tA~ MMaaddee AAvvaaiillaabbllee bbyy 33MM ffoorr IInnssppeeccttiioonn aanndd CCooppyyiinngg aass CCoonnffiiddeennttiiaall IInnffoorrmmaattiioonn:: SSuubbjjeecctt ttoo PPrrootteecctiivvee OOrrddeerr IInn PPaallmmeervrv.. 33MM,, NNoo.. C22--0044--66330099 22881133..00002222 3MA10053207 3MA10053207 Page 21 Figure 1 : MMeeaann LLoogg CCaarrbboonn=-1144 LLeevveellss ((NNoorrmmaalliizzeedd ttoo aa IL ST SR 10 mg/kg Dose) in Liver and Plasma of Rats (Groups of 3) at 1, 2, 4, 6, 161ind 32 Days fagRNR RE hy Post Oral Dose of N-Ethyl FOSE- C in Feed 100- 3| : :aQ- E) Liver Liver jig N-Ethyl Plasma ------ 17 22I 44I668I 86I 1JI1o 112i2 11144 11I66 11I86 22I00 22I2 24I4 22I86 22I6 3010 3R12 0 DAAYYSS POSTDOSE 33MM CCOONNFFIIDDEENNTTIIAALL Made Avaiable oy 3 for Inspacton ana Copying as Confidential Information Made Available by 3M for Inspection and Copying as Confidential Information: SSuubbjjeecctt ttoo PPrrootteeccttiivvee OOrrddeerr IInn PPaallmmeervrv.. 33MM,; NNoo.. CC22--0044--66330099 28133..000023 AOS 3MA10053208 Page 22 CARBON-14 LEVEL IN LIVER/CARBON-14 LEVEL IN PLASMA Figure 2 5Is- Ratio of Carbon-14 Level in Livar/Carbon-14 Level in Plasma of Rats (Groups or 3) at 1, N2e,pt4h,yl8,ro1s6,e j1%rd 3in2 DFaeeyds Post Oral Dose of N-Ethyl roSE- C in reed : I gZ Je10- 2 & 2 5 | Zz 5S- -- / El & | TTTEYERRETEE I 0 30~221 4460dI 03i112I011i42 11I481i16 81r0 2Dr0 2 2I2 H 2r4 3Wr DMr I3r0R3t2 ODARYYSS PPOOSSTTODOOSSEE 33MM CCOONNFFIIDDEENNTTIIAALL Wade vata tor nspecton sn Copyng 3s Content formar Made Available by 3M for Inspection and Copying as Confidential Information: S`Suubbjjeecctt ttoo PPrrootteeccttiivveeOOrrddeerr IInn PPaallmmeervrv.. 33MM,, NNoo.. CC22--0044--66330099 22881133..00002244 ountonsazoe 3MA10053209 Page 23 Figure 3 : Thin-Layer RRaaddiioocchhrroonmaattooggrraanm of of EExxttrraaccttiioonn FFrraaccttiioonn 11 Thin-Layer (ether) Eluate B (1:1 chloroform-methanol) Pre-adsorbent SGF Uniplate: 100 chloroform 35 methanol . Tct.al CPM on Plate = 1,125 5 ammonium hydroxide OF TOTAL CPM ON PLATE . " E zo 3 E gw e 5& . B 7 122 33 445 5 66 7780 8911001111 1122131415 DDIISSTTAANNCCEE FFRROOMM OORRIIGGIINN ((CCMM)) 3M CONFIDENTIAL Made Available by 3M for Inspection and Copying as Confidential Information: SSuubbjjeecctt ttoo PPrrootteeccttiivvee OOrrddeerr IInn PPaallmmeervrv.. 33MM,, NNoo.. CC22--0044--66330099 281133..00025 3MA10053210 nase 20 Page 24 Fiore 4 : TIThhiiinna-eLtaatyyheeerrr)RRaadHdiiaootcFshihergeoue3mrmaeatt(o4oGgs1r3saamnehooifforEIoxaottrremasoccnttieiooinnnaFFnrreaalccttiioonn 1 2 Peenstscrbent scr Uniplate: 10505 emehtlaoarnoettorn (acid ether) Eluate 8 (1:1 chloroform-methanol) Pre-adsorbent SGF Uniplate: 100 chloroform 335 Semen methanol bydronide 5 mmmonium hydroxide Sota Gov on Piste = 4,363 Total CPM on Plate = 4,363 ] = PERCENT Of TOTAL CPM ON PLATE gZz8 w40 | = & EE 3=a- b & En20- &g | . 1 | Or '-2 aPe1IoeDIe3SeTA4eNCesE F6TROT7M OasRIG9eIN10n(1G1H)w12n13n1i4 s15 DISTANCE FROM ORIGIN 11011) am COnNagFIDENTIAL SMMuaabddjeeecAAtvvalaoialPabrbollteeecobtyyiv33eMMOrfoodrrerIInnIssnppePecacttlioomnneaavrnn.dd3CC.ooppyNyoii.nnggC2aa.ss0CC4oo-nn6ff3iidd0ee3nnttiiaall IInnffoorrmmaattiioonn: Subject to Protective Order In Palmer v. 3M, No. C2-04-6309 22881133..00002266 wAt00s3211 3MA10053211 _--Page 25 to _ Figure 5 Thin-Layer Radiochronatograrr. of Extraction Fraction 3 (1:1 chloroform-methanol) Eluate B (1:1 chloroform-nethanol) Pre-adsorbent SGF Uniplate: Total CPM on Plate = 664 100 chloroform 35 methanol 5 ammonium hydroxide . . So PERCENT OF TOTAL CPM ON PLATE Zo 0 . 3 E g2 5 s8 2. B& I) o Fed Yosos--ryogeromnsroney 2 3 4 5 d 7 Q 9 10 11 12 13 14 15 ODISTARNCE FFRROOMM OORIGIN I(GCM)I 3M CNFE~~~p AL Made Available by 3M for Inspection and Copying as Confidential Information: SSuubbjjeecctt ttoo PPrrootteeccttiivvee OOrrddeerr IInn PPaallmmeervrv._ 33MM,, NNoo.. CC22--0044--66330099 28133..00027 3MA10053212 Peasgee 2266 Go - FFiioguurree 66 Thin-Layer Radiochromatogram of Extraction Fracticn 2 (acid-ether) Eluate B (1:1 chloroform-methanol) Pre-adsorbent SGF Uniplate: 100 butanol 10 water 10 acetic acid Total CPM on Plate - 1,650 50 - EEg P 40- E3 E 11 8gE3Y0 $a ! 5 20- 2 w10- || 0 404OQ(-, 5-1sO l122 33 4 4 556 5 77 0 8 0 8 1100111111221133 11441155 DISTANCE FROM OORRIGIN ((CCMM)) sn 3a1mA GCOOkNlkF.I1DEVN1TIAALL Made Available by 3M for Inspection and Copying as Confidential Information: SSuubbjjeecctt ttoo PPrrootteeccttiivvee OOrrddeerr IInn PPaallmmeervrv._ 33MM,, NNoo.. CC22--0044--66330099 28133..00028 3MA10053213 Page 27 w || ESg e OF TOTRL CPM ON PLRTE CE || 1 2 i 1 B5E. I4] | | U w EAJ CL | 0 Figure 7 Thin-Layer Radiochromatogram of Extraction Fraction 2 (acid-ether) Eluate 8 (1:1 chloroform-methanol) Pre-adsorbent SGF Uniplate: Total CPy on Plate = 1,474 100 chloroform 100 methanol 2 acetic acid ? PT ohEnne 04-oPg0q0a000200000R000e% S00 -1 0 1 2 3 4 S E 7 e 0 10 11 12 13 14 15 DISTANCE FROM ORIGIN ((CCMM)) 3M CDHFIDEINTIAL Wade Made Avalabl Available by by 33M fo for Inspection Inspection and and Copying Copying as as Confidental Confidential Ifnofromramattiioonn: SSuubbjjeecctt ttoo PPrrootteeccttiivvee OOrrddeerr IInn PPaallmmeervrv.. 33MM,, NNoo.. CC22--0044--66330099 28133..00029 aMAtoosa214 3MA10053214 Page 26 Page 28 60- Figure 8 Figure 8 hTFhiriannc--tLLiaaoyyneerr1 RRlaaedgshiieoorcc)hhrrooEmmlaauttaootggeeraaAnm (oocffhlEoExrxtotfrroaorccntt)iioonn Fraction 1 (ether) Eluate A (chloroform) PPrree--aadcss:u,rrbbeenntt SGF Uniplate: SGF Uniplate: 11003005 cnchehltlchoraronofofolorrrmr anmoniua hydroxide 35 nethanol 5 ammonium hydroxide Total CP on Plate = 4,983 Total CPN. on Plate = 4,983 OF TOTAL CPM ON PLATE 5E0l-4 = Ta'.X 3 = & E2 w 31) e & g= 20 U 1W0 / 0 40133358676 p0i11221niss -1 0 1 2DDII3SS'TTA'4ANNCCSEE FF5RROOM7M OO0RRIIGG0IINN10((CC11HM)) 13 14 13 3M ginc MMaaddee AAvvaaiillaabbllee bbyy 33MM ffoorr IInnssppeeccttiioonn aanndd CCooppyyiinngg aass CCoonnffiiddeennttiiaall IInnffoorrmmaattiioonn:: SSuubbjjeecctt ttoo PPrrootteeccttiivvee OOrrddeerr IInn cPaallmmeervrv.. 33MM,, NNoo.. CC22--0044--66330099 22881133..00003300 | 3IMMAA1100005533221155 . .aQe -/~ rie3 Figure 9 vinegar Sadiosheomstopru of Betsetion Thin-Layer Radiochrematogram of Extraction Fraction 2 (acid-ether) Eluate A (chloroform) Seemstsrtent Sor wnipletes 10%0ScshelaoEtroefrormytronsen Pre-adsorbent SGF Uniplate: 100 Chloroform 35 methanol roead com on piste = 1.020 Total CFM on Plate = 1,020 5 ammonium hydroxide so- ]50- gu 3Zu'10 _~ =& | E=30- $ || 55 i 20- wo] PER EERE NNER] 0. 260002 20600600000% 15000 2 3 4 5 6 7 0 9 10 11 12 13 14 15 DISTANCE FROM OORRIIGGIINN ((CCMM)) | 3M CCONUFI~DE?!NTa IAL Wade Avalabl by 3fo Inspection and Copying as Confidental formation Made Available by 3M for Inspection and Copying as Confidential Information: SSuubbjjeecctt ttoo PPrrootteeccttiivvee OOrrddeerr IInn PPaallmmeervrv._ 33MM,, NNoo.. CC22--0044--66330099 281133..003311 MAt00s3216 3MA10053216 Figure 10 | TThhiinn--LLaayyeerr RRaaddiioocchhrroommaattnoggrraanm ooff EExxttrraaccttiioonn FFrraaccttiioonn 33 (1:1 chloroform-methanol) Eluate A (chloroform) Pre-adsorbent SGF Uniplaze: 100 chloroform 35 methanol 5 ammonium hydroxide || TToottaall CCPFMM oonn Fllaattee == 11,,221166 | ] -| I .:;I g : | Eg A; g8 e iilJr! 2 8 ie; | Ea s | tiO 5 6, i 20 ' II; v N~ :t9l | 'I i OTR TE J senna us I 1 2 3 4 5 6 7 6 9 10 11 12 13 14 15 DISTANCE FROM ORIGIINN ((CMM)) i | 3WM CCOONNFFIIDDEENNTTIIAALL. 1' ym ------ S`MSuaubbdjjeeeccAttvttaooilPParrbooltteeeccbttyiivv3eeMOOrrfoddreerrInIIsnnpePPcaatllimomeneravrvn..d33CMM,o,pNNyooi..ngCC22a--s00C44o--n66f3i3d00e99ntial Information: 28133..00032 AT0053017 3MA10053217 "| rove Hawes 31 Page 31 Figure 11 | ri taper adiochomatoneam of Bxtcaction Thin-Layer Radiochromatogram of Extraction | TE ee oe hrevetors Fraction 1 (ether) Eluate A (chloroform) [SI %Bveere ie Pre-adsorbent SG? Uniplate: 100 butanol 10 water 10 acetic acid cote cm on Piste + 2.079 so -- .Total CPM on Plate a 2,879 v SO - HI 4 z= E z=V -- 3 i 20 g A1I a A REE TER -1 0 1 2 3 4 5 0 7 0 9 10 11 12 13 14 15 DDIISSTTAANNCCEE FFRROOMM OORRIIGGIINN ((CCMM)1 A CONFIDE11a L Wade Avalabl by 3fo Inspection and Copying as Confidental formation Made Available by 3M for Inspection and Copying as Confidential Information: SSuubbjjeecctt ttoo PPrrootteeccttiivvee OOrrddeerr IInn PPaallmmeervrv.. 33MM,, NNoo.. CC22--0044--66330099 28133..000033 amAt00sa218 3MA10053218 Paargse 352 FFiigguurree 1322 TIFhhaiivrne-eiLioaanyyeerr1 RR(aaedbtilhooaccn'iisrEeohmruaaattcoosgsrsaem(eoonfftoEErxxottsrroaarccntt)iioonn Scematsorsent SCF tnipiste: Fraction 1 (ether) Eluate A Pre-adsorbent SGF Uniplate: (chloroform) 113000006 ccshenlstonorarnooeftdoorrmn ?100 meeetrhiaenolsie 2 acetic acid Total Ca on Plate = 2,082 Total CPM on Plate a 2,862 eg =z5ze : 2 9 Eg 4 o5 i 5 PERCENT OP TOTRL CPM ON PLATE 10 & EE EAS EERE 01--ooecpesoccporeed Se600000 --1 0 1 2 3 4 5 6 7-- a 9 10 11 12 13 14 15 DDIISSTTARNNCCEE FFRROOMM OORRIIGGIINN ((CCMM)) ETAL i Mm ~CO1R:FIiBENTIA s- Made Made Avaable Available oy by 3M 3M or for Inspecton Inspection and and Copying Copying as as Confidential Confidential IInnffoorrmmaattiioonn: SSuubbjjeecctt ttoo PPrrootteeccttiivvee OOrrddeerr IInn PPaallmmeervrv.. 33MM,, NNoo.. CC22--0044--66330099 28133..00034 AT003210 3MA10053219 ! Appenatx 1 = Table 1 Appendix 1 - Table 1 Thin-Layes Chzanatogeashy Systems for NeEehyl FOSE-IC Thin-Layer Chromatography Systems for N-Ethyl FOSE-!4C PPlvloaa.ttee SySSosolttvveeenrnttt No. System RRfeb2 of n-zehy FosE-Tic of N-Ethyl.F0SE-14c 1 1 111000000 caehcnletotorornooeffoorrnm om 0.70 100 acetone 2 2 111000000 csehneltcoohrreoonftoootrrmn 0.90 0.90 2100 msectehtiacnolacie hl 2 acetic acids i 3 3 11555000 cmehnelttoohrraoonftooolrrnm . 0.50 0.90 | 550 mwemtnhoaninoonl hyaroxiast 5 ammonium hydroxide | . 4 11030500 mceehntlthooarrnoooftloorrmn . 1.00 1.00 fi 535 meemtshoaninuoml hydroxiacS 5 ammonium hydroxides || s 5 100 100 babuutzteaarnnoorl om 0.77 1100 waacteetric aacciieds 10 acetic so SGSoooltlvuveeennntttssmwivexerrteeurpeprreveappsaarreesddagevvsoollutmmoees:tvvhooellucumhmeresa;maato11s00r00apmmhllyaalSliainqqkuu.oott of of bo RssgRifrocfiaeleptviihisaenycnootffppamllcamimaitaxdtaeyteo.ou.arrrned((>ws>am9s3p88o48an))didueppmedesahkktyodorotonnxhitetdhheceehrtwtohehmiriaenn-t-lolcagaoyryneeacrrpenhctcyrhhatretaooenmmdaka.t.toon- Acetic acid and ammonium hydroxide were concentrated. Notebook Raterence: NB-51806-41-62 Notebook Reference: NS-51806-41-42 au nEETEAL, SMMuaabddjeeecAAtvvaatoiillPaarbbollteeecbbtyyiv33eMMOrffodorrerIInnIssnppeePccattliioomnneaarvnn.dd3CMC,ooppyNyoii.nngg2a-ass04CC-oonn6ff3ii0ddee9nnttiiaall IInnffoorrmmaattiioonn:: Subject to Protective Order In Palmer v. 3M, No. C2-04-6309 22881133..00003355 3MA10053220 3MA10053220 minyayer Ragsochroratostan of N-thy) Appendix 1 - Figura 1 RTFohOiSsnEe--~4yCerDDoosRsiainndggioScSohorlluoutmtiaiotonon,g,rPaPlmlaaottfee NNN-ooE..th11yl sre-atsorbent SCF Uniplate: 100 chlosoforn Pre-adsorbent SGF Uniplate: 100 chloroform 100 acetone Tota con on Pate = 5,22 @go- Total CPM on Plate = 5,393 so PERCENT OF TOTAL GPM ON PLATE n70- 2 z3 so- Eel | SEEs oso- ||I 2 | 40 g= 30- [| . ny & | 20- | to- | ETT S 33 15 6%f6 oi7 ls -1 0 2 3 4 S 6 7 S 9 10 11 12 13 14 1S DDIISSTTAANNCCEE FFRROOMM OORRIIGGIINN ((CCMM)) --_-- --,,_- . . MMaaddee AAvvaaiillaabbllee obyy 33MM ffoorr IInnssppeeccttiioonn aanndd CCooppyyiinngg aass CCoonnffiiddeennttiiaall IInnffoorrmmaattiioonn: S`Suubbjjeecctt ttoo PPrrootteeccttiivvee OOrrddeerrIInn PPaallmmeervrv.. 33MM,, NNoo.. CC22--0044--66330099 2881133..00036 amAt0053221 3MA10053221 appendix 1 = Tigure 2 Appendix 1 - Figure 2 hin-igyer Rodiochronstogean of N-Ethrl TTohsine-J1i2yerDDoossRiianndggioSScoohllruuotmtiaiotonon,g,raPPmllaaottfee NNo-. Eth2 yl No. 2 FOSS- C Pre-adsorbens SCF Uniplate: 100 chlocoforn Pre-adsorbent SGF Uniplate: Tota) con on Plate = 5,310 3002 mSeetahralneolsee Total CPM on Plate a 5.310 100 chloroform 100 nethanol 2 acetic acid PERCENT OF TQTRL GPM ON PLATE :. | 8 Es | 2 8gw &E. Bg i} 0--1 00 23.33 f455 58.7.78 E 89 11001111 1122131114451185 DDIISSTTAANNCCEE FFRROOMM OORRIIGGIINN ((CCMM)) ay AanETIN Gi EE MMaaddee AAvvaaiillaabbllee obyy 33MM ffoorr IInnssppeeccttiioonn aanndd CCooppyyiinngg aass CCoonnffiiddeennttiiaall IInnffoorrmmaattiioonn: S`Suubbjjeecctt ttoo PPrrootteeccttiivvee OOrrddeerr IInn PPaallmmeervrv.. 33MM,, NNoo.. CC22--0044--66330099 2881133..00037 33MMAA1T00005533222222 Appendix 1 - Figure 3 re Si ony pias vor 3 Thin-Ijyer Radiochromatogram of N-Ethyl FOSE- C Dosing Solution, Plate No. 3 Pre-adsorbent SGF Jniplate: 150 chloroform 50 methanol | 9C-- 'total CPM on Plate = 5,356 5 amnonium hydroxide PERCENT OF TOTAL CPM ON PLATE | . ||| .,0W:- 70- || FEE w | z so- Exso- 25[40- 30- ]| i 20- w10-6 E aAANa NEAA ACY 00. 2 3 4 g 0 7 a a 10 11 1122 1133 1144 1155 DISTAHNCE FROAM ORIGIN ((CMM)) 3 a v * 4r Wade Avalabl by 3fo Inspection and Copying as Confidental formation Made Available by 3M for Inspection and Copying as Confidential Information: SSuubbjjeecctt ttoo PPrrootteeccttiivvee OOrrddeerr IInn PPaallmmeervrv.. 33MM,, NNoo.. CC22--0044--66330099 281133..00038 aMAT0053223 3MA10053223 Sppantin 1 = Figure 4 Appendix 1 - Figure 4 hin-tqper Resioshionstossan of Wehr Thin-Jiyer Radiochromatogram of N-Ethyl Fora sototion, Fases Wo. FOSS- C Dosing Solution, Plate No. 4 Pre-sdsorbent Sr Uniplate: 10505 TeSrehmtlemonazinoootsnornyecorite Pre-adsorbent SGF Uniplate: 100 chloroform 35 methanol 5 ammonium hydroxide Zeta cow on Phase = 3% Total CPM on Plate - 5,154 PERCENT OF TOTHL CPM ON PLHTE | || n i i 3zzw60 Ew5D E 40 5 Ew30 E= 010 k-Eit0e1os2a3.35TA6SNCM5E F6MROAH7 O0RIG0OIN1E0(IC11HC)12E1X3 TI4 %IS ciSTANCE FROM ORIGIN (CM) | a1 SoRFzEl 3M sme TiAl ~~~.~gi~ d jam. ~;i/A~b r' SMMuaabddjeeecAAtvvlaaoialPabrbollteeecobtyyiv33eMMOrfodorrerIInnIssnppePecacttlioomnneaavrnn.dd3CC.ooppyNyoii.nnggC2aa.ss0CC4oo-nn6ff3iidd0ee3nnttiiaall Information Information: Subject to Protective Order In Palmer v. 3M, No. C2-04-6309 22881133..00003399 MAT0053224 3MA10053224 | AAppppeennddiixx 1 1 - = rigors Figure 55 Thin-flyer Radiothromatogram of A-Ethyy FOSS- C Dosing Solution, Plate No. 5 | 10 acetic aci Pre-adsorbent SGF Cniplate: 100 butanol 10 water 1C acetic acid } go TToottaall CCPPMM oonn PPllaatta? = = 5,258 5,258 90 8D - PERCENT OF TOTAL CPM ON PLATE w 7n0 ZEg w 3 W5= a so 5s2gRo i| & 40" || 30- | g 20-1 .1 0 0I-1T0 12 Z 3 3 44 5S60 77 608 991100 1111 112211331141155 DISSTTAANNCCEE FFRROOMM ORIGINN ((CCM)) 3aEm RMs CPOANEEFIIITDIeoEL - Mads Available oy 3M for Inspecton and Copying as Confidential Information Made Available by 3M for Inspection and Copying as Confidential Information: SSuubbjjeecctt ttoo PPrrootteeccttiivvee OOrrddeerr IInn PPaallmmeervrv.. 33MM,, NNoo.. CC22--0044--66330099 28133..00040 3MMAAT100005533222255 Aopendix 2 Appendix 2 DDbeetteeenrcgmeaiilnnaaFttOiiSooEnn- oo1ffcCCaaDrzobbnooenn/--r11e44eCCooMnnittxetenuntrteooff N-Ethyl FOSE-14C Dose/Feed Mixture cFFCSiiooovvnnmeeeeesseoanllaaeinniogddqfuuoppotatatetsdheeEogdletfaoosnnttehh)eesafeddffeiooisvsvreeee-/-s/pfpifleiieaeeqddccueeotmmsiiasxxnnttvaluaulyrrryeeetidicvewcaetealrreleecubbwiawaelnelaieianggdnchhceeeeb.dd.y ciiTTnonhhttneeoobacttctaaeairrreoebbddnoonnc--vco1ai1mdmt4bbhuusc&ttiioonn cP8FiTao4nacn.itkt1feiae8oarcnrdmt(ensMyMoeofoesdLeAAetolppwhlppeee3t3ndn00h8d6odiisiooOexxsnx/sifih44aedoieiosasdnztnedderart.Al.AhpipeppqeeuRcRnnoeeoddcctmiioosbxvxvueewsrra44tyysi-=oodonTTffeatsaebacslrlraaemepcrilbbnoeo11enn))d.--.si1edt4b,TTyhvwHciaatsogsshmubdsdrrueeeesttcctteeohoirrevvommeeniirrdnnyyaeewtdidawvtaahtsscwooeaebbee Cuonrirfeocrtmeldy using this cecovery foctor. low throughcut the combustion recovery factor. sample set, thus the data were corrected using this a 2 PDpaoacrckmkeaerrrsd GIIrnnoscvtteer,mismeeTnnittiCCnooammpp.aannyy,, Inc., Inc., 2200 2200 Warrrreennvviillllee Wa Rost, Road, Downers Grove, Illinois. i 3M CORFInEpRTnLS 3M CjJJ'yy': G COL j{SJ c~v`G:N :I t $e A3i SMMuaabddjeeecAAtvvataoiillPaarbbollteeecbbtyyiv33eMMOrffdoorrerIInnIssnppeePccattliioomnneaavrnn.dd3CMC,ooppNyyoii.nnggC2aa-ss0CC4oo-nn6ff3iidd0ee9nnttiiaall IInnffoorrmmaattiioonn: Subject to Protective Order In calmer v. 3M. No. C2-04-6309 22881133..00004411 3IMMAA1100005533222266 Appendia 3 = Table e 1 1 CCaarhboonn--1144ACCpDooponsentente/denrintextceoo2ff-MiWNTx-iatEubthrlheyal FOSE-1C FOSE-14C Dose/Feed Mixture 15 werehyt FosEC equivatents/s ug N-Ethyl FOSE-14C equivalents/g 23.08 5s2ss3..e6t9 ser 535.61 sin 517.61 5s1s7e..a307 559.24 : overant Fe 0.72 17.58 + 17.58 Overall x 530.7 Votebook Reference: KB-51806-45 1M-51806-45 Notebook Reference: | | AMm CCOONF*IlB"EE~R~TveIAL SMMuaabddjeeecAAtvvataoiillPaarbbollteee cobtyyi v33eMMOrffdoorrerIInnIssnppeePccattiiioomnneaavrnn.dd3CCM,ooppyNyoii.nnggC2aa-ss0CC4oo-nn6ff3iidd0ee9nnttiiaall Information Information: Subject to Protective Order In Palmer v. 3M, No. C2-04-6309 22881133..00004422 NOS 3MA10053227 repenatx 2 Appendix 3 RRDaaattseWW/eeriieggahthttsMsixaatnneudrAAemmooAuudnmntitnoiofeftNNe-roEetdrhyntlo FFbOaoScshEE-1R-a4MCt Dose/Feed Mixture Administered to Each Rat ToentRniaafttication st WTWieemiiegghhtotf((Jg6)o)ve FAsemeoosuunWntitri((og6)t)eooffCoDDroooissmeee//d DboemssHee/KSiinn Identification at Time of Dose Feed Mixture Consumed mg/kg n 236 wa 10.07 1A 236 in pi he 1B 221 io Bt EH 1C 242 Py 3 ws 10.29 2A 231 3 i U3 lolz 2B 220 x om 8 Toros 2C 237 as en 10.30 4A 315 a 3 oh reed 4B 329 " FH BH jie 4C 327 " 210 sa 10.28 8A 270 ins oa jroert 8B 289 & FH 5 wk 8C 286 en 20 sae 10.21 16A 280 ia 25 ptt 5 16B 289 ee iH on fied 16C 276 mn an os 10.30 32A 317 i 200 5 freed 32B 309 Se 0 Hi60 100.2:015536 32C 301 4.48 4.24 3.61 10.07 10.18 7.92 4.48 4.26 4.49 10.29 10.28 10.05 6.11 6.37 6.34 10.30 10.28 10.29 5.23 5.61 5.58 10.28 10.30 10.28 5.42 5.61 5.35 10.27 10.30 10.29 6.15 5.99 5.84 10.30 10.29 10.30 x + S.D. - 10.13 + 0.56 Notebook Reference: NB-S6531-165-8 and 3-51606-46 Notebook Reference: NB-56531-16b-s and bB-51806-46 . 3M1mA CONFIDENTIAL SMMuaabddjeeecAAtvvaatoiillPaarbbollteeecobtyyiv33eMMOrffodorrerIInnIssnppeePccattliioomnneaavrnn.dd3CMC,ooppyNyoii.nnggCa2a-ss0CC4oo-nn6ff3iidd0ee9nnttiiaall IInnffoorrmmaattiioonn: Subject to Protective Order In Palmer v. 3M, No. C2-04-6309 22881133..00004433 3MAT0053228 3MA10053228 Appendix 4 Determination of Recovery of Total Carbon-14 From Blank Biological Samples Spiked With N-Ethyl FOSE-14C For each of the four sets of samples combusted, five replicates of 10 t:l, 50 vi, and 100 ul of diluted N-ethyl FOS-14C dosing solution were aliquoted with calibrated nicropipettors directly into scintillation vials. At the same tine using the sane solution and pipets, either five or six replicates of 10 ul, 50 u1, and 100 ul were aliquoted directly into combustion cones containing 1 g blank biological material (fecal, liver, spleen, or muscle homogenates;. The ccxebustion cones were dr+ed and then pelletized with 5 cm ashless filter paper. Blank filter paper pellets were corr.busted and the soiventcs collected in the vials to which the FC-95-14C had been added directly. One of each of the 10 ul, 50 tl, and 100 ul N-ethyl FOSE-14C spiked pellets were routinely combusted at the beginning, midd'_e, and end of each set of samples. After correction for background and counting efficiency, percent recovery was calcilate-3 by comparing mean results from direct addition and combustion. The recovery data for four sets of samples that Mere analyzed on different days for total carbon-14 (N-ethyl FOSE-14C) are shown in Appendix 4 - Tables 1-4. The mean recoveries for the four sample sets are 84.18, 92.78, 93.38, and 95.08. The recoveries were uniformly low throughout the c.=,'^ ;-n sample sets, so the data were corrected using the appropriate recovery factors. 3M CONFIDEHTIAL Made Available by 3M for Inspection and Copying as Confidential Information: SSuubbjjeecctt ttoo PPrrootteeccttiivvee OOrrddeerr IInn cPaallmmeervrv.. 33MM,. NNoo.. CC22--0044--66330099 281133..00004444 3MA10053229 repent 4 = Taste 1 Appendix 4 - Table 1 Recovery of Toss Costonctd Prem Blane BBiioollooRggeicicocavalelrSSyaamompfpllTeeosstSaSplpiiCkkaeerddbWWoiintt-hh14NNF--rEEotthmhyyBlllaFFnOoksSEE--l144cC,, Copmansion set vo, 1 Combustion Set No. 1 Commune Spiked Bicteptent Soles Combusted Spiked Biological Samples veces _pesns _pucns vives iver biver 7X3eo6offPLosicavvueesrr Feces Feces Feces Liver Liver Liver and Feces 1100uls8 115566332b 1t6ee4s8 1s6z82 11775500 1n74e8 17 713 on ems mm me me wes ws Ts 50 ul 8328 8329 7768 8219 7605 7475 Joos wen ses vss se en wes sist i 100 ul 16381 14905 15581 15724 15693 14498 11668844 7954 15464 ow wn wsimzesswagnasssowneswptvese 13s 10 ul wa am mss sss ses ows sexe 50 ul ou wn wes ese ise ee on 100 ul Direct Addition Samples 1917 1907 1912 1946 1962 9547 958 9609 9605 9819 18943 18415 18654 19154 18741 x 1929 9628 18781 wu PI 100 10 ul 50 ul 100 u1 wh11668884 x5 110000 -= 8877..3309 1929 wn3798554x4x 110000 -= 8822..6609 9629 To 11S544E644 x4 110000 -= 8822..33%8 18781 Opnwcrat 5 2 5.0. recovery vse for corcection of cxieizes Overall x + S.D. recovery used for correction of oxidized samples - 84.1 + 2.88. 2[dosr nt ofoeep s Poa BE-1C apiking solution added A Amount of N-etl,yl FJSE-14C spiking solution added. F Notas Retesence: XB-51006-44 Data are expressed as dpm. Notebook Reference: NB-51806-44 31A CONFIDENTIAL Made Avaiabie oy 3 for Inspscton and Copying as Confidential Information: Made Available by 3M for Inspection and Copying as Confidential Information: S`Suubbjjeecctt ttoo PPrrootteeccttiivvee OOrrddeerrIInn PPaallmmeervrv.. 33MM,, NNoo.. CC22--0044--66330099 281133..00004455 MATOS:5230 3MA10053230 rppenstx = zante 2 Appendix 4 - Table 2 feceneey of Tora Cashon-14 Prom Blatk BidloRgeiccoavlelrSSyaaommpfpllTeeosstSSappliiCkkaeedrdbWWoiintt-hh14NNF--r2EtothmhyylBllaFFnOOskSzE--l1i4cC,, Biologica Ein tet ve. 2 Combustion Set No. 2 JE commanted Spiked Bictogicnt Samples Combusted Spiked ee Biological Samples Spleen sprees mescle Muscle Liver SSploefen Woaerle usLeilveesss Spleen Spleen Muscle Muscle Liver z of Spleen x of Muscle zX ooff SSpplleeeenn,, muscle, and Liver wa ms en sw sm ems es sm on 108 1t6es5t0?: 1t8es922 11770011 1v6e2222 11998e5s 1177M1 16166611 11480066. 10 ula 50 ul 9392 7837 9397 9387 8775 8615 9392 8927 100 w1 1864s 1188661133 1166330066 ---- Z2 1199113355 1188662259 1166330066 1188002233 i 100 ul 18645 owi} wes mesisecutmacoiviwonssazpwless nxse 10 ul su own ees ses me en sere 50 ul teow ws ems ese wes toa je 100 ul 1933 9877 19743 Direct Addition Samples 1938 1713 1925 1919 9829 19735 9863 19546 9861 . 9931 19523 19338 x 1886 9876 19577 ou 10 ul ou 50 ill wo100 vl ose11880066 x4 110000 -= 9955..7766%% 1886 sere Terr 3899227x7x 110000 -= 900..3366s9 9876 118800223 3xx 110000 -= 9922..006608 19577 GSreerains Ti+n5.5. cecovecy sed for corzection of oxidizes overall'; + S.D. recovery used for correction of oxidized samples - 92.7 + 2.88. 2 amount of Heaths PFOOSSEE--1144CC apiing spiking vsoolluuttiioonn sddec. added. a Amount of N-ethyl [E legn ionnsetthpeVgtiin ner sees. : b Data are expressed as dpm. o Spiking error; sample was not used. Votebosk References 1B-53102-46 Notebook Reference: NB-53102-46 aa SNFTi1~EERarTppint S Eto . MMaaddee AAvvaaillaabbllee obyy 33MM foorr IInnssppeeccttioonn aanndd CCooppyyiinngg aass CCoonnffiiddeennttsiaaIlnIfnofromrmaattiioonn: SSuubbjjeecctt ttoo PPrrootteeccttiivveeOOrrddeerr IInn PPaallmmeervrv.. 33MM,. NNoo.. CC22--0044--66330099 28133..00046 3MMAA1D00S53E23N1 Appendix 4 - Table 3 Tp RTT Recovery of Total Carbon-14 From Blank Rn Biological Samples Spiked With N-Ethyl FOSE-14C, Combustion Set No. 3 1100 ule 5s0ouml Combusted Spiked Spleen Spleen 119e7762: 22007m1 99553300 -=-=SE Feces 22008844 1100334477 ETT Biological Samples x of 'x of x of Spleen Feces Feces Spleen. Feces and Feces 22008522 11897799 22002255 22003388 22003322 1100006611 1100004439 99553300 1100115522 9s8ee411 | SA : 100 ul 18332 18070 18944 19641 19778 18201 19454 Direct Addition Samples 18828 x | 1100u0l 22005500 22005555 22008855 22008877 22110055 22007766 50 ul 10624 10664 10609 10525 10466 10578 100 ul 21668 20617 21263 20810 21253 21122 | --_--10tul --E50e ul s, ---- 100 uel ee 2032 x 100 - 97.99 2076 9841 x 100 - 93.0% 10578 18828 x 100 0 89.19 21122 | OOvevraellrz a++SlS..0lD.. rreeccoovveerryy uusseedd ffoorr ccoorrrreeccttiioonn ooff ooxxiiddiizzeedd samples a 93.3 + 4.48. | 2 p suount ofy ethr pose apthing sclueion added. a Amount of N-ethyl FOSE-14C spiking solution added. b c Dspaitkainagreererxoprr;essssaaemmdppllaees wdwapagsm.nnoott uusseedd.. Spiking errors scorn even on Notebook Reference: NB-53102-53 OHFIDEHTIAL. 3~1 Made Available by 3M for Inspection and Copying as Confidential Information: `SSuubbjjeecctt ttoo PPrrootteeccttiivvee OOrrddeerr IInn PPaallmmeervrv.. 33MM,, NNoo.. CC22--0044--66330099 2881133..00004477 3MA10053232 Appentin 4 = Table 4 SioioRKgeeicceoonnvteecryyECAaonpoRfefpmietTTennoodettiiaxasolplpnii4CCnk-oeaescsrdeTsebaowWonbinineclct-.1heh1d4NB4F-TerErtotemhnoynBBlllaaFFnnOkkSOE-S14,C, Biological Samples S Combustion Set No. 4 Contented spikes pioleptent swmies Samples Combusted Spiked Biological ot itner x of Kidney Kidney Sane Money peces feces "sd Paces Kidney Kidney Kidney Feces Feces and Feces out sad aes wo ma me am | 10 ula 2420b 2386 2210 2341 2310 2333 ow me ve ee vse em 1s 50 ul 11892 11876 11344 11584 10782 11596 ow ames mus mem mee aes mes 100 ill 22569 22444 22622 22867 21969 22494 ow an smizeect aemasetionwsanmplesws w5e 10 ul on vas mm mm one ww os 50 ill ow men wes aes wen wm wen 100 ul 2412 11299 24816 Direct Addition Samples 2394 2384 2413 2425 12222 12232 12214 12127 24405 24269 24873 24753 x 2406 12019 24627 ou su 10001 10 vi 50 ul 100 ul Tue223333343x 110000 -= 9966..997748 2406 ao Tn L111S59966 xx 110000 -= 9966..44880* 2222449434xx 1yCc00 -= 9511..334408 12019 24627 orvieceant T= 350.0a. sIecYovery snes or correction of oxizized Overall z + S.D. recovery used for correction of oxiiized samples - 95.0 + 3.18. 2Ba AaRmoouunLtt ooffceNo-sretetoshyty)eldPFOOaSSnEE--do11n44.CC spiking spiking solution solution asded. added. NbotDebaotoak arReeteezxepnrceesssed1a-s5EdSpHmI.-1D Notebook Reference: NB-56531-10 Made Avaable oy 3M for Inspecton and Copying as Confidantal Information Made Available by 3M for Inspection and Copying as Confidential Information: S`Suubbjjeecctt ttoo PPrrootteeccttiivvee OOrrddeerrIInn PPaallmmeervrv.. 33MM,, NNoo.. CC22--0044--66330099 2881133..00048 3MMAA110000553322533 Appendix 5 - Table 1 Toad Total ECCV-oarErkbtbohoanyne-l-1a14FP4nOOSSiiEDnnEo--gFFT1eeAe4,cCCceessii1nn0AA.tFfF1tee3taueerdFdr3/ttaaknonoa)OOHKrraaatatlasl Dose Dose of of (Mean Dose, 10.13 rg/kg) || | PeCcrooirlotldeeccttBiiaooynne) itPeriod (Days) x Rat Rat I1ddee3nnteiitfiiccaattiioonn T A B C dems si Ad Mean + S.D. || ot nae Tas [REP 11 DDaayy GGrroouupp 432.1 474.7 + 219.9 0-1 712.88 279.3 | o02-r1 4Bs5eu1.ss5 2 2 DDTaaoyymeGGrroouupp aoe 352.8 Mw28ie1.zs2 3m16e19.s8st+ 8eE5sn.s5 i 1-2 374.4 302.6 209.5 295.5 + 82.7 or m0 4oDTraNyyEeGcrrooupp 20.6 29.95 M3 :is :t |i| 0-1 j=1-2 p=e2-3 251.0 Goz ams 204.2 Se eas sl teen 194.4 178.0 238.5 184.7 320.6 ls 247.8 llezs 163.2 249.9 Y mei mo 230.2 + m1s0e3 a1l60s 180.8 + 71.3 23.0 16.0 3-4 114.4 159.0 146.0 139.8 + 22.9 || 0o-r12 6wP.sl6 oay rove. 8 Day Group so 229.6 e1n2n7y.y7 21u40n15..o09s%+ 280a920.e48 peF23=e~ --d243 fr53sB925eao309.t..su135 fr53a1ar278sl994e...os]006 248.3 2 225.7 T2a3n 172.7 305.9 + 249.4 warms 371.4 + 170.9 mamelesE awvies 226.8 + 83.6 4-5 ps5-6 =ore6-7 150.4 Vials 119.6 77ss 97.5 142.8 59.4 99.4 wGoal 68.7 92.3 sa 96.2 eSlse98.0 128.5 + say 105.1 + emeael 88.1 + 31.6 112.7 ztens16.8 7-8 75.3 44.2 86.9 68.8 + 22.1 | 6 oso 1166TDaaRyyYGGrroouwpn vse 828.82 613 0-16 1906.0 1797.8 1782.6 1828.8 + 67.3 || | r0ce--11n66 2s0s8s5oo.0 3222TDDaaEyyEGGrroouupp ns 1513.8 1s75nG7gr.6 117s885e5..e55 ss+a2at8o6e.ss6 err-------------------------------- 16-32 93.0 295.8 81.7 156.8 + 120.5 2 DoDaalttlaaesaatxrieeoneexxppperrreeissoasdce.dd as as vg ug Neathyd N-ethyl POSE FOSE-14C equivelenee//ssaamnpilee equivalents collection period. Woebook Refezences: 18-51806-50, NB-55673--2360--3323 NB-55673 -51806-50, Notebook References: NB 3M CONFIDENTIAL SMMuaabddjeeecAAtvvataoiillPaarbbollteeecbbtyyiv33eMMOrffdoorrerIInnIssnppeePccattliioomnneaavrnn.dd3CMC,ooppNyyoii.nnggC2aa-ss0CC4oo-nn6ff3iidd0ee9nnttiiaall IInnffoorrmmaattiioonn: Subject to Protective Order In Palmer v. 3M, No. C2-04-6309 22881133..00004499 3IMMAA1100005533223344 | Iopamtx 5 = Table 2 Total Total Appendix 5 - Table 2 CECaairrnbbooenns=-114F4oiSinnE-UU4rrciinneeinAAffPtteeenrrd aatnno OORrraaatlsl Dose Dose of of `Mean Dose, N-Ethyl FOSE-14C , 10.13 pena) in Feed to Rats 10.13 mg/kg) (Mean Dose recCrooinlctlaeeccttGiiaooynne) ee Period (Days) x sat Rat Iodeenn=ttiitfsiccaacttioonn T A B C mezsamo Mean + S.D. or ast TESS an nes 0s 1 Day Grcup 0-1 3.158 2.73 2.11 2.66 + 0.52 !I 2 Day Group or 23 Ea 26s 28s 0.60 0-1 3.30 2.11 2.65 2.69 + 0.60 fe) 2% i IN Inion 1-2 2.16 1.71 2.18 2.02 + 0.27 00-1 je1-2 =2-3 =3-4 0-10-1 21-2 pe2-3 fy3-4 os4-5 ss5-6 &6-7 =7-8 oe0-16 sn 3.72 pe4.67 52 3.72 on4.71 2.862.86 Zn 2.34 204.20 wie 10.42 ie8.46 2 2.45 ie 2.63 pr1.78 Hse 70.34 4 Day Group T33.31 pe4.62 13.31 i 3.25 8mayGrove 8 Day Group Tos2.05 Sis3.95 33.31 2s2.60 we8.34 Vas1.85 is1.51 Va1.37 1166DDaaByyAGGerroovupe 35.46 2763.76 NE 3.62 3% 3.76 Im 3.22 a23.12 Loe 4.08 Use 4.86 38% 3.53 32 3.12 3a2.47 pig2.92 2.81 M27 31.27 260s 08 3.60 + daE ols 4.30 + seE os 3.50 + unioo 3.73 + 0.25 0.59 0.25 0.85 26s 06 2.68 + aaex ois 3.46 + dni oom 4.12 + smi oan 5.52 + der als 6.64 + 226k ois 2.26 + 2.35 + NSE en 1.99 + 0.56 0.97 0.78 4.27 3.05 0.35 0.74 0.74 5.5620.908 45.69 + 21.45 02 EXT 50.07 653.138.519 0-32 60.36 32 Day Group 85.44 50.07 65.29 + 18.19 2 Dpiaaettcaataairreeoneexxppperrreeissossdee.dd an as vo vg Neethyd N-ethyl FFOOSSEE--144CC eeqquuiivvaalleennttss//smaemsppllee collection period. Noteboookk RReeffeerreennccee:: NN3B--5511680066--5512--5555 Notebo 33M CONFAIDEERRIIS SMMuaabddjeeecAAtvvataoiillPaarbbollteeecbbtyyiv33eMMOrffdoorrerIIInnssnppeePccattliioomnneaarvnn.dd3CMC,ooppNyyoii.nnggC2aa.ss0CC4oo-nn6ff3iid0de9ennttiatalall IInnfforoIrnmfoartmaitoionn: Subject to Protective Order In Palmer v. 3M, No. C2-04-6309 22881133..00005500 J fg 3MA10053235 sepnte Appendix 6 AST Bn TR Carbon-14 Content in Digestive Tract (plus contents) and Feces After an Oral Dose of N-Ethyl POSE-14C in Feed to Rats (Mean Dose, 10.13 mgAg) Rat Identification 1"Aw 1B 1C Mean + S.D. Time PostDose %Hours) 2244 24 24 Digestive Tract (plus contents) Feces 11.e8s5-ta 6644..0084 31.98 105.79 8.54 57.38 17.46 + 12.69 75.74 + 25.24 2A 48 8.51 91.79 2B 2C Mean + S.D. 48 12.37 115.74 48 8.12 44.15 9.67 + 2.35 83.89 + 36.44 2a Dpaattaa aarree eexxpprreesssseedd aass uugg NN--eetthhyyll FFOOSSEE--'1i4CC eeqquuiivvaalleennttss//gg.. Notebook Reference: NB-51806-49-50 ay COUFIUEwR--TIEaS 31A ~,~b Made Available by 3M for Inspection and Copying as Confidential Information: S`Suubbjjeecctt ttoo PPrrootteeccttiivvee OOrrddeerr IInn PPaallmmeervrv.. 33MM,, NNoo.. CC22--0044--66330099 22881133..00005511 3MA10053236 ropenatx 7 Appendix 7 Compazative dacs Shoving Norra Fecal Excretion for Rare Comparative Data Showing Normal Fecal Excretion for Rata AApo5p5peennTddaitiexx. 7 7 -r= oTTmaasbblleeof | 1 fsashchoeoswves eccxoocmmrppeaatrreaadttiibvyvee rddoatatstaa ss%shhoo2wv4iinnhggavennoorri.innatalelrfvfeaelccsaall feeoxrxccrreett7iioonn fdcZSSoaOhoorIyonLutTrrppGoaootLtlsshsattt.igdgorronoostsGuuehprpeeasppmeefsrcieiiincnoooaddlfpprrfaeaceercvvrceeiieeootgssuuisisivevosexesntncntruuedfdfstioioaereretdssesrr(aba(yFttoFssfCe-r-EaiEicxntnarpsvpeteterhhariitiiismsnne2es4nnsttttthushusidogsuyy88rsaaaaennmindddndytfe9f5)or)o.srv.rraelrfsTaPachhttofesasmosspreeuausreedaacddabo7tlteaaa3s3 sLh2o7wEnethaetxctrheetifoencaflateesxcroeftiroantsrawteeesd aof croanttsroiln tshteiwspsstuidny 2aortehecrompsatruadibelse: :o the excretion rates of rats used as control groups in 2 other studies. 1 - 3anMf COpRARNEDREERNTTIIAAlL SMMuaabddjeeecAAtvvaatoiillPaarbbollteeecobtyyiv33eMMOrffodorrerIInnIssnppeePccattilioomnneaarvnn.dd3CMC,ooppyNyoii.nnggC2aa.ss0CC4oo-nn6f3ifd0ie9dnetinatl IInnffoorrmmaattiioonn: Subject to Protective Order In calmer v. 3M, No. C2-04-6309 22881133..00005522 3MA10053237 3MA10053237 Aopenatx 7 - Tabte 1 Appendix 7 - Table 1 Gonpacative Data Showing Norse) Fecal Excration for Rats Comparative Data Showing Normal Fecal Excretion for Rats Collection 3 Sxfae+ssS.fpDr.onooffthe PCeoriloldectGiaoyne) 3prreastesntfrosmeltyhe Period (Days) present study Faspors x + S.D. of 5 contfol rite frm control rats from ome 8 FC-Exp. 6 cozntF+raoSls.oDr..atooefffs5rom mor control rats from PC-Exp. 9 ot 0-1 8e.s0 2.6 + = a b 2.68 1025s+ 3.60 10.29 3.61 2 sues nocd [RIN 5.00 2.20 .-2 9.47 + 2.96b 7.79 + 1.58 = esa nuE weanszo sos 0 2-3 10.79 + 1.14 10.27 + 2.04 mt mersost wasn seers } 3-4 11.61 + 0.910 10.33 + 2.22 77.0.4 2+0443.0388 9.00 + 2.21 8.30 + 1.20 9.74 + 1.25 ss sesame sanz 9.572 1st 4o-s5 8.5922 + 22..4477E8- 88.55112+ 2.63 2.63 9.15 9.15 2+ 0.86 0.86 i 5-6 9.78 + 2.17 9.11 + 1.79 9.57 + 1.54 16-7 1100..6699 5+ 11..2277L8 88..6655+2 1.93 1.93 8.62 8.62 2+ 1.07 1.07 EEab 20TDDTha5aitt2saa dGdaaaaarctetetaha'eexxiiippsnnrrefefEssrrossooneemmddttthaahhesees g2g36rraDaDBmamaassyyy GGoGorffrrooofuuufepppeccooeeofffss tetethxhhxciiicssrsreetstssetetxdduueddyppy..ee,rr collection collection pericd. period. This data is from the 8 Day Group of this study. Notebook References: Notebook References: N1BB5--35566155033211--211566u0--2119660vu0aannadynd116462d43dd--1166nhhh,, ndand NB-53102-29t-29bb and 42q IIn 3M CURAlFI-i- | MMaaddee AAvvaaiillaabbllee bbyy 33MM ffoorr IInnssppeeccttiioonn aanndd CCooppyyiinngg aass CCoonnffiiddeennttiiaall IInnffoorrmmaattiioonn: S`Suubbjjeecctt ttoo PPrrootteeccttiivvee OOrrddeerr IInn cPaallmmeervrv.. 33MM,, NNoo.. CC22--0044--66330099 2881133..00053 33MMAA1100005533223388 Appendix 8 Carbon-14 Content in Tissues After an Oral Dose of N-Ethyl POSE-14C in Peed to Rats Olean Dose, 10.13 iDg/Rg) Rat Red B1000 Bone Digestive Subcut. Abdom. Identification Liver Spleen Kidney& Lung& Cells! Plasma-a Karroo! Tract! Carcases ?at! ?at! Muscle! 1A 1B 1C Mean 32.55 49.58 24.75 3S.)9 6.77 7.00 4.80 6.19 8.93 14.65 6.76 10.11 8.13 11.89 6.16 8.73 21.95 27.73 20.35 23.34 7.36 10.61 6.13 8.03 1.40 15.00 8.73 12.04 11.85 31.98 8.54 17.46 2.29 3.23 1.61 2.38 6.44 7.93 3.99 6.09 8.10 9.68 4.87 7.55 1.79 2.21 0.97 1.66 2A 28 2C Mean 4A 4B ^. Mean 31.25 42.95 41.58 38.59 5.93 ..:.1 7 30 6.01 44.42 44.95 40.34 43.24 6.75 7.62 6.84 7.07 6.89 8.22 10.49 8.53 6.39 6.75 8.80 7.31 19.38 20.66 12.31 17.4S S.69 6.54 9.S1 7.25 8.82 11.29 9.82 9.98 8.30 9.08 7.81 8.40 18.83 21.44 19.90 20.06 7.76 9.10 7.92 8.26 10.72 1.3.89 11.41 11.01 8.21 10.07 8.92 9.07 8.51 12.37 8.12 9.67 - b - - 1.47 1.98 2.40 1.95 4.07 4.30 3.97 4.11 3.35 4.10 4.30 3.92 1.13 1.65 1.38 1.55 b - -- 2.21 3.07 1.67 2.38 2.14 1.80 1.79 1.91 1.63 1.40 1.36 1.46 &BA 88 BC Mean Mi 26.81 24.65 34.52 28.66 sme 2.15 1.80 3.98 3.34 3.45 6.33 2.64 4.37 of2.87 2.62 6.52 4.01 I8.42 7.68 12.61 9.57 MEO2.94 3.24 5.66 3.95 3.36 2.91 5.63 3.97 TZ -- - -- - -- -- -- on0.54 1.01 0.71 0.75 Bh0.38 0.23 0.48 0.36 aw0.34 0.25 0.98 0.52 16A 16B 16C Mean 20.97 28.67 27.09 25.58 0.83 0.87 1.11 0.94 1.93 2.05 3.07 2.35 1.47 1.61 2.36 1.68 2.24 3.04 3.25 2.64 1.75 2.19 2.92 2.29 0.99 -- 1.01 - 1.52 -- 1.17 0.03 0.04 0.16 - 0.13 0.01 0.16 0.36 0.03 0.21 - 0.17 0.03 0.18 32A 328 32C Mean 20.25 33.18 20.95 24.99 0.76 1.37 0.64 0.92 1.86 3.57 1.80 2.41 1.66 2.45 1.36 1.82 0.83 2.65 0.89 1.46 1.9S 2.87 1.59 2.14 0.69 - 1.50 -- 0.63 - 0.94 - 0.08 0.00 0.13 - 0.28 0.00 0.29 -- 0.06 0.00 0.09 0.14 0.00 0.17 b Data are expressed as ug N-ethyl POSE-14-1 equiv4lents/g. Sample was not taken. Notebook References: NB-51806-47-49, NB-53102-43-44, 47-52, and 54, NB-56531-11-12 3H CONFIEERTIAL .n-3.1a 4 L'. Made Available by 3M for Inspection and Copying as Confidential Information: S`Suubbjjeecctt ttoo PPrrootteeccttiivvee OOrrddeerr IInn PPaallmmeervrv.. 33MM,, NNoo.. CC22--0044--66330099 22881133..00005544 3MA10053239 Eeom)ia TECHNICAL REsPOsRT SUMMARY /wm{)47-5tn :1Vil~:tv ~ :. TECHNICAL REPORT SUMMARY OX TECHNICAL COMMUNICATIONS CENTER = 201K TO;TECHNICAL COMMUNICATIONS CENTER - 201.2CN part 1mri 5 confpp, dw opr 9TOC) )portanr --Ifreport isprbtted an both sides ofp*w,wnd ttev copies to TC'C.1 -- Sune 5. 1981 ~ y June 9, 1981 Dv1Wn CONTIAL RESEARCH LABORATORIES, dnalyeical and Properties Research CENTRAL RESEARCH LABORATORIES, Analytical and Properties Research a wilec t ServRtggEteMier = Taal _Service to Riker - _1$g2ation of Trace Plugrochemicals er lusrosctane Sutfonie Acid. - A Mat-Liver swoo'l7.n*. Perfluorooctane Sulfonic Acid - A Rat-Liver gate. 2074 = vetanelice of Teal = due 9, 1981 AR No. 7474 - Metabolite of FM-3422 - June 9. 1981 To Soli - 82-02 S. .1, rib-son. J. D. Johnson - 218-2-02 A,,thorfT Sov. Taphre ------------ S. V_ Pathre r>rov000t Atwr * wweontvh STCURITY10. BX comiamier RorRemonion L ov.n (Company Conlidentiw) Ciosed (Special Autiwriaation) | PHERIR>T 3{A CHEMICAL REGISTRY low- Numbw Laboratory| 0502 Laboratory 0502 re /'Clad Number 200007 A000007 ame 'Am o'I N'mhe, a474 --- amoloree Numbe.(s) 233150 233150 emer No. vi Fog"Inctuohne Cowrtneet 33 Bae New ChemKala Reported 0 Yom Q No KEYWORDS: IEE (so4w twine from 3164 Thataurvs. Suypest other appbude term.) po Project to. 91505026 C.RLAP etycicat Report|| MeeREor = 5. J. Gibson, J. Du Johnson Analytical Report cheated Analyte TPA T FETTLTRrEsTe rReR ie SveCot rrenti e Chemical Analysis CURRENT OBJECTIVE: Request No. C57427 i Request No. C57427 Project No. 91505026 Requestor - S. J. Gibson, J. D. Johnson AiORT AMSTUACT:(206250 words)That sbevact inform Tien it dittritwted by the Technical Commun"tiont Center to alert 3M'en to Coeitpw v R&D. It it Company cortlidentid rrutriat. eAA irrdaact-n-ylliiyvreerromameet.taabboolliictee Lo is densified identified an as perfluorooccttaannee perfluoroo sulfonic Sulfonic acid by I ~P-Nlgt. | ---- Informsthorh L siso't lnrt b"' 41cCoOnNFFIIDOEENNTTIIAALL, 3 33MM CCOOHMFIgBErNIIAL SMMuaabddjeeecAAtvvafaoiillPaarbbollteeecobtyyiv33eMMOrffdoorrerIInnIssnppeePccattliioomnneaarvnn.dd3MCC,ooppNyyoii.nnggC2aa:ss0CC4oo-nn6ff3iid0dee9nnttiiaall IInnffoorrmmaattiioonn: Subject to Protective Order In Palmer v. 3M. No. C2-04-6309 22881133..00005555 3MA10053240 3MA10053240 rm ce CENTRAL ANALYTICAL LABOORRAATTOORRYY LAB CENTRAL, ANALYTICAL ReeppoorrttNNoo.. couene74J724ucennas R Datenei Junne S~naa 1n10288n1 e Date poe Subjects Subject: PPeerr{fll+uug3orroogoecCctiaaannnee Salford SulfoLic Requestor: JS.. DJa.IGOibWsosn. . Actd = A Bav-Liver Nesabotace te of of Acid - A Dept. RAt-Liver Name oo Metaboli M8. cenee Pi-322 FM-3422 Proj. NoRIOSE IQo91505026 PRES ZT -- Requestor:__.tL_D,_Zg1U"D__ Vert. Name ----1UW Dated . Resspbsr 100 OK... Proj, i Requeet No. _ W:J;Z___- ____ Dated __1ZP_Ce7bf=_:Q. M30--- Report: VTuFTewM2or-o0e3m4m2ee2l7tt2aaabbwbewoaloelrelriedeitteestssnuusbbzim1iisai-tooCttllHteaIaedsCtdeIed-dffHooefrrfOrrHososmmppeeelctctuhthtetrereoosdlLsciicovavopneepidrriccooTffaa1n-naaCaaHllyyryTsaasittiesls.aua.dtcues:.dTii.Tnhnieeissssceeteerrtteewwddoo m1Ce4-tCla-albbaobleeillteeedds metabolites were labeled as I-CHI CI-YeOH eluted qc and II-CH3 TH2CH 3 eluted. CPAP C7: (CF2CP)-3Cl-2-CCCiHs2FOOHH I-CF2 CF2 N-CH CF3CF2-CF2(CF2) mena FM-3422 Expertaencal Experimental iBMoomttphh16sssaammappllreeess ovwebertreaeinrreeecdcoonnossnttiitcthuuecteVedadriifran,nCCDKDy3-001DD0..0 TTahnhede X119L7F--2-N00M0RNsAsRppeecscptterrcaatrooonnsettthheeersssee samples were obtained on the Varian XL-100 and XL-200 NMR spectrometers. Newaboliittee I11"7FF t0iBt 11336677550N NMeectaabbooiltce TITI 1117F RNMGR 330011990O%X Metabolite Resse | Results hT"pheeectccrhah.eemasicrcaeallgsisvhheiinffcteh*el((oppvpp.mm uuTpphffeiieelpldedskffrrofommreCCqFFuCCsLn1yc3)i)esooffarttehheenmomarajmjoaorlrizppeeedaakksstoIi8nn(CttFhh1ee) ffl=luuoorriinnee #10 poe. spectra are pm. given below. The peak freauzncies are normalized to 6(CF0 81.0 p 1 BLO M3 114.3 112000.44 11221L.S5 112222..44 112266..00 | 1mom81o.0 ms 112.9 102 120.2 28 121.8 112:22,88 162 126.2 II 81.0 Discussion Discussion SBBooettthhibessippieetccettrraa metacboomlpiartiengI vvwtwaeheasrerseeiLrdedttefeyynepnptritiieciccnacaaclallelooffttIoo.FppepepWrerefrfrRlflfululouou(roro1oror1oooo2coco5tctc2atat)nanaeneneoesfsususlluutffllhoefofnonoynnylliilacctddteeaearcrcriiiidvvdvaiattaatihsisvveddegseesa.tta.eterrnmToTiifhhnneeeeIdd. by comparing the reference "F *M (11252X) of the latter with Ciat of I. Fy = CCFF2 ---- CCFF2 o-m- ((CF22))y3 ---- Ts.:F2 ---- CCFF2 ---- SS0O3MH BCLFO3 ---1260 112222..44 LL5 121.5 104 120.4 16 114.3 81.0 126.0 @(I) TThDchhhheeeeeeomtusitoppceeeeatccleTttdrrsaihuuhiamiEff.eootff0oofctfphhmeetthhemmeienettffTaaliTbbu,uooool1lrr0iioo4ztmmeesepttpIhIhmIyIyullpvewefananiseeseivvaaeelelrorpfynyhreaosSmiEfttmSooLihLltteeahhrerestn ststTouou.llffttoohhTnanahytytelloo1fgfg1rr2oIoI.uup9eep.xx.pccpeeuppIIttttpeihitasheke, observed at 112.9 ppm in II, 1.4 ppm upfield from that in I. The 112.9 ppm peak, _ a2ng p5anE=T9IRT,I.-TV_,I~A+L 1&, SMMuaabddjeeecAAtvvataoiillPaarbbollteeecbbtyyiv33eMMOrffdoorrerIInnIssnppeePccattliioomnneaarvnn.dd3MCC,ooppNyyoii.nngg2-aass04CC-oonn6ff3ii0ddee9nnttiiaall IInnffoorrmmaattiioonn:.- Subject to Protective Order In almer v. 3M. No. C2-04-6309 22881133..00005566 ALG 3MA10053241 a -- * JJAuuRnneeNo9.9,.711499788411 vee 7 Page 2 sichaush not usesbtguouaty, can be assfgned to the alpha fluprosechylene oaoflfthttohheueghssuullnffoootnnaaummniiaddmeebi(g(-u-SoS0u02;sNNlHHyy,2))caggnrrooubupep::assigned to the alpha flucromethylene . = a = ( an = nons-- soa Us -- CF2 -- CF 3 -- (CF2)s -- CF2 --- CF2 -- 112.9 S02NH2 conctusion Conclusion he Lover mecabolice Liveled HCL HOR fn densified sn perfluoroscsans i TssuhulelfflooninivicecraaccmiieddtaaabnnoddlitttehhaatLtalblaeablbeeedlleeddI-ICIHI1C--1CME3C-C11M,e3OiHississsuugiggdgeeesnsttteieddfieaadss appseerrpffellruufoolrruooooorccottoaacnnteeane Hl fms t sulfananlde. S50. rates | sorS. V. Pathre | SVP/ra | 3M SoCaAmeFsE | Made Avaiabie oy 3 for Inspscton and Copying as Confidential Information: Made Available by 3M for Inspection and Copying as Confidential Information: S`Suubbjjeecctt ttoo PPrrootteeccttiivvee OOrrddeerr IInn cPaallmmeervrv.. 33MM,. NNoo.. CC22--0044--66330099 2881133..00057 amAto0ss242 3MA10053242