Document xKdjpxoOrK0ZMD0vpo1aV6jb

Pim Corporate Health Physics Seu 3M Center, Building 2202802 AR226- . 0009 Attachments to April 21, 2000 letter to C. Auer from W. Weppner (Dermal Absorption and Intravenous Pharmacokinetics in Rabbits) 3M Technical Reports 1. Single-Dose Intravenous Pharmacokinetic Studyof T-6246 in Rabbits. 3M Environmental Laboratory Study # AMDT-042095.1 2. Single-Dose Dermal Absorption/Toxicity Studyof T-6049 in Rabbits. 3M Environmental Laboratory Study # AMDT020895.1 3. Single-Dose Intravenous Pharmacokinetic Studyof T-6049 in Rabbits. 3M Environmental Laboratory Study #AMDT-112294.1 000077 IMne4dduiMscetidrniieca,aHHlyeDgaeileptnaerP,hmTyesoniectsoogy SP3OMtBCoolxne5sM,2N2B0i5d1i3n3g3222200-202 STII Dermal Absorption and Intravenous Pharmacokinetic Studies in Rabbits Mmaatneryioaflsthwehipcrhodaurcetbaeplpileivceadtitoonhsafvoer l3iMmitfelduocraopcahcietmyicfaolrsdienrvmoallveabhsiogrhp-tmioonl.ecuHloawre-vweeri,ght hlaovwe-mmoolreceuclaapra-csietiyghfotrmdaenrumfaalctaubrsionrgptrieosnidaunadlsmdetoaebxoilsitcicnovnevreyrssimoanlltoamounts which may apbesroflrupotriooonctaanndestuolfesotnaabtlei.shIpnerofrldueorrotoctbaentetseurlufnodneartsetaanndd fthleuolriimdietsfoofndaesteacdteaqbuialtietymaorfkers owfitdherpemraflluaobrsooorcpttainoensouflmfaonnautfeacatnudrtiwnog irenstirdauvaelnso,uas lpohwa-rdmoasceokdienremtailcasbtsuodriepstiwoenrsetudy undertaken in New Zealand white rabbits, ZTeoadleatnedrwmhiinteedreatbebcittisonwelrimeitdsosfeord tihnetdraevremnaolusalbysowriptthiodneisotnuidzye,dinwdaitveirdu(aclonftreomla)l,eoNr e0.w003, a0n.0a6l,yzaendd f0o.r3tmotgalPoFrgOaSni/ckfgluaonrdidheeulsdifnogrt4h8erhmoaulrse.xLtriavcetriosnamopflfelsuotraikdeenbayt mteeramnsweorfae `OmroidoinfiEeAd9D4o0hrEmxapnanndDabXl2e0I0o0nOArngaalynziecr.HalTihdee pfroelsleonwceedobfypearnfalluyosirsoofcotrafnleusourlifdoenuastienginatnhe 0s.p3ecmtgro/skcgopayn.dL0i.v0e6rmtogt/alkgordgoasnei-cgfrlouuoprilnievecrosnwceanstrcaotnifoinrsmaetd4w8ithhouerlsecptorsots-pdroasyemwaesrse 1.0 afonrdp0e.r6flpupormofoocrtatnheesu0l.f3oannatde0a.n0i6omngb/ykgcldecotsreod-sapnriamyalmsa,srsessppeeccttirvoeslyc.opySpyeiceilfdiecda0n.a6lyasnids d0.o3sepdpamnifmoarltsh'e l0i.v3erasnddid0.n0o6t mcgon/tkagindoqusaendtiafniiamballes,lerveeslpseocftifvleuloyr.idTehaeb0o.v0e0b6aacnkdgr0o.u0n0d3. `The method was determined to be capableofdetecting a dose between 0.01 and 0.06 mg/kg. wInerteheedxepromsaeld adbesromrapltliyonunsdtuedry,octchlrueseiomnalfeora2n4d-thhorueres fteomaanleaaqlubeionuosrsaubsbiptesnspieorndoofse0.g0r6oup. pheelrdcefnotrp2e8rfdlauyos.rooLcitvaenressualmfpolneatsetaaktednoastesteerqmuawlertoe0a,n0a.l0y0z3e,d0f.o0r6,toatanldo0r.g3anmigc f/lukogriadned uHsailnigdethfeorlmlaolweedxtbryacatniaolnysoifsfflourorfildueorbiydemeusainnsgofanaOmroidoinfEieAd94D0ohErxmpaanndnaDblXe20lo0n0 Organic ASnianlcyezeitrw.asThdeermeonwsatsrantoeddeitnecatraabblbeittotianltroarvgeannoiucsfplhuoarrimnaecoakbionveetibcacsktgurdoyu(nTd-6i2n4t6h)e tlhivaetrsa.n 1 000078 . CCoorrppoorraatte HInedaulstthriPahlysHiycgsiene & 3FOM BCeonxte3r5.2B2u0ilding 220-2602 ErCgoorpnoormaitcesOccupations Medicine S6t5P1a7u3l3 M11N10S5133.3220 C3oMrpMoerdaitceaTloDxiecpaalrotzmyent ipenrtfrlauvoernoocutsadneossuelfoofnat0e.06imn g2/8k-gdadyidporsets-uldtosien detectable livers and fluoride as well a doseof0.012 as mg/kg was not detectable, it can reasonably perfluoroctanesulfonate was be concluded that present at 28 days less than 20 percent of the applied post-dermal-dose. The low dose levels in this study preclude an absolute determinationofabsorption or non-absorption. aInnaolrydseirs ttoo dmeotneirtmoirnaebtshoerpfteiaosinbiolfitfylouforuoscihnegmiccoamlbsutshtaitomnafyolcloonwveedrtbmyetflauboorliidcealiloyn to pgeirvfelnuobryoictnatnreasvuelnfoounsatienjaefctteironde1r0mraablbiatbss.orGtrioonu,ppseorfflfuoourromctaalneesaunldfofnoautref(eTm-a6l2e46n)ewwas. czoenatlraonld),wohrit0e.r0a0b6b,i0ts.0(1H2r,a0:.(0N6ZoWr)S0.P1F2)mwge/rkegdopseerdflwuiortohoecittahneersudlef-oinoantiez.ed Twawtoera(nviemhailcsle perermsaeixninpgertdwooseangirmoaulpspweerrseesxchpeedrudloesdefgorrosuacpriwfeirceeosnacdriafyic1e4d oponstd-adyos2i8npgoastn-ddotshieng, dBalyosodpowsats-dcooslilnegctfeodr atthe4,288,-d1a2y, 2sa4crainfdic4e8anhiomuarlss,.anLdiv8eranwdas15codlalyesctfeodrfaoirl raanbabliytssi,saantdth2e8 m1e5aannsdo28fa-dmaoydisafcireidficDeos.hrAmnaanlnysDiXs2w0a0s0peOrrfgoarnmiecdHuasliindgetfhoelrlmoawledexbtyraacntailoynosifsfflouroride by fSleugomriednetuesdiFngleoitwhAenraalnyzOerriwointEhAi9on40seElexcptainvedaeblelcetrloodne.AnTahlyezaesrsaunmdpttihoen,Skbaalsaerd on past `wmoornki,torwiansg mtoatdaleftlhuaotripdeerfwlouuolrodcptranoevsiudlefaonnaatdeeiqsunaottemmeetaabnoslitcoadleltyecdtegarbasdoerdb,edand that fdeltueocrtoacbhleemilceavle.lsoTfhfelutowriodel.oweTrhdeorsaebbgirtosueprsu(m0.h0a0lf6-lainfdeo0f.e0l1i2mimnga/tkigo)ndfiodrntohte 0h.a0v6eand 0.012 mg/kg values in the dose 0.12 mggro/ukpgsdwoesreegcraolucpuldaitdednoats 28 days and demonstrate 48 days, respectively. much change between The liver the day 15 post-dose sacrifice animals liver concentrationoffluoride and was the day 28 1.48 ppm. post-dose sacrifice animals. At day 28, the liver fluoride At day 15, concentration wsiagsnif1i.c2a3ntplpymg.reaTtheerrtefhoarne,28badsaeyds.onIntahidsdiltiimoint,editdwaatas,ctohnechlauldf-eldiftehaitn 0r.ab0b6itmgl/ivkegr is ppoesrtf-lduoosreo.ocTtahniesssutlufdoynaetsetarbelsiusltheedd iantmheraesshuorladbloefdleitveecrtcioonncefnotrrtahteiocnosmabtustwteinotny-meeitghhotd,days confirmed the ulyofliver total fluoride measurement as a marker for transdermal ) 000079 C`Coorrppoorraattee IHensdlutshtrPihaysHiycgsiene & CEorrgpoonroamtiecsOccupations Medicine C3oMrpMoerdaitceaTloDiecpualrotgmyent P3OM BCeonte3r.32B2u0ilding 220.26:02 6St5.1Pa7u5l 1M1N1053133.3220 aexnpdocsounrfeitromefdlutohreocehxetmeincdaeldshwahlfi-clhifegoefnesrearteumpearnfdluloirvoeorcetlainmeisnualtfioonnatien atshearmaebtbaib,olite, TMehteh3odMolStorgayteagnicd TdoexteicctoiloonglyimLiatbsohraavteoriymhparsovbeedgusninacesetrhieessoefssttuudideiseswetroeduenvdeelrotpaken. pceormfplauroarobclteandeastualofonnadteer.maTlhfelsuex eoxfapersiermieenstsofutfilluiozreoachreemciocnasltsi,tustteadrthiungmawintehpithelial pceurltfulrueor(oRoEcpta)naevsauillfaobnlaetefrsotmudSykiisnEctohmipcl,etNei,cea,cForpayncwei.ll Wbeheprnovtiheded 3 000080