Document e7Ym9a5NQJp6EEjMnz6KDjQJq

- R22 -0 y Attachments to Letter to C. Auer dated May 4, 2000 A 15 Perfluoroctane Sulfonate Studies Pharmacokinetic Studies 1) Skin Absorption Studies on Surfactants (1983) ) Report from W. C. summarizing data McCormick to D. R. Ricker, dated September 26, 1983 b) 28 Day Percutancous Absorption Study in Rabbits with FC-95, Safety Evaluation Laboratory, Riker Laboratories, Inc., Experiment No. 0979AB0632 (FC-95) ) 28 Day Percutaneous Absorption Study in Rabbits with FC-99, Safety Evaluation Laboratory, Riker Laboratories, Inc. Experiment No. 0979AB0633, 3M Reference No. T-3988.1 (FC-99, diethanolamine salt of perfluorooctanesulfonate, assumed to be 25 % in water) 2) Single-Dose Intravenous Pharmacokinetic Study of T-6053 in Rabbits, 3M Environmental Laboratory in water Lot 130, Unit 177. (FC-99, 0.04 % diethanolamine salt FC solids in water), of perfluorooctanesulfonate November 16, 1995. Final Report - Analytical Study, which includes copy of in vivo Study No. AMDT- 010495.1, Hazleton Wisconsin, No. T-6053.1 Inc., Project No. HWI 6329-136, 3M Reference 3) ESinnvgilreo-nDmoesnetaDlerLambaolraAtbosroy,rpSttiuod/ny NToox.icAiMtyDTS-t0ud2y21o9f5T.-160(5F3C-in99R,abdbiietts,ha3noMlamine salt of perfluorooctanesulfonate in water Lot water), November 22, 1995. Final Report ~ 130, Unit Analytical 177. 0.04 % FC Study, includes solids in vivo in Study Hazleton Wisconsin, 6053.2 Inc., Project No. HWI 6329-137, 3M Reference No. T- 4) Fluorochemical (FC) Levels in Naive Rats, 3M Medical Department, Toxciology Services, Study No. T-6316.9, DT21, Draft Report for Objective 3, May 14, 1999. 5) Analytical Data 2000, including submitted to Dr. Jennifer Seed, USEPA, by letter dated May serum measurements from two in-life studies: 3, 4) A1n1a1l,ytwiictahlrdeastpaecftrtoomOArdavla(nGcaevdagBei)oaPnhaalyrtmiaccaolkiSnerevtiiccesReSctouvdeyrNyoS.tuFdAyCoTf-TOX- Perfluoroottane Sulfonate 3M Reference T-6295.14. in Rats, Argus Laboratories Protocol No. 418-015, 03726 Attachments to Letter to C. Auer dated May 4, 2000 = Perfluoroctane Sulfonate Studies b) A1n1a0l.y,tiwciatlh draetsapefcrtotmo AOdravlan(cGeadvaBgieo)anPahlayrtmicaaclokSienrevticiecsSSttuuddyyoNfoP.erFfAluCoTro-oTcOtaXn-e Sulfonate in Rats, Argus Laboratories Protocol No. 418-013, 3M Reference T6295.12. 6) In Vitro Comparative Metabolism Study in Rat and Human Hepatocytes with Various Fluorochemicals, 3M Reference T-6295.1, study of T-6292 (N-ethyl FOSE), T-6293 perfluorooctane (N-ethyl FOSE monophosphate ester), T-6294 (N-cthyl sulfonamide), and T-6295 (Perfluorooctane Sulfonate) a) Range-finding Cytotocity Assay, SRI International Toxicology Laboratory, Study No. B010-95 - protocol and faxed results dated Oct. 26, 1995,Dec. 12, 1995, and Jan. 16, 1996 b) Metabolism of T-6292, T-6293, T-6294, T-6295 by Rat and Human Hepatocytes, SRI International Toxicology Laboratory, Study No. BO11-95 ) Advanced Bioanalytical Services, Inc., Analytical Report, Additional Characterization of Metabolites of T-6292, T-6293 `Human Hepatocytes by TurbolonSpray LC/MS and and T-6294 from Rat LC/MS/MS. Semi- and Quantitative Analysis of T-6295 in Rat and Human Hepatocytes Incubated with T6292, T-6293 98AGKPO1.3M and T-6294 by LC/MS/MS, January 28, 1998, Report d) WMoetrakbionlgisImnteirnpRraettatvsi.onHoufmRaesnulHtesp,acthoacrytteesn,tiutlpeddatPeedrfFleubo.ro5s,ul1f9o9n8ambiadseed on ABS Jan. 1998 report OC7R7? = Internal Correspondence oo rei FF.ADL. UGsreidf,fiMt.hD.- -202-02-82-60-202 --) To D. R. RICKER - COMMERCIAL CHEMICALS DIVISION - 236-2B-01 Fam W. C. MCCORMICK = MEDICAL, TOXICOLOGY SERVICES - 20-28-02 Seioct Skin Absorption Studies on Surfactants am Date: September 26, 1983 LAtatvaocrhaetdoryareontthheefidnearlmalreptoorxtiscitfyroamndRikaebrsoSrapfteitoyn Esvtauldiueasticoonnducted on FC-95, FC-98, FC-99, FC-128, FC-129, FC-134 and FC-135. Eraacnhgestfuidnydevrasstcudoyndufcrtoemdwhiinchthedosfeosllvoewriengsemlanencetre.d, tFeonllmoawlienganad Ten female rabbits were clipped free of hair and the test article was place on L40% of the total body surface area. An impervious fpelsatstiacrtischleeetvaoscclruedmeovdedt.he Askniinmalfsorve2r4ehomuarisntaafitneerd wahnidchobtsiemrevedthe for a 28 day period. Blood samples were obtained on days 1, T, 14 and 28. Analysis of day 1 and 28 fluorine levels were made for a Gsaiynglbeodmyalweeigahntds fveemraele refcoorrdeeadc.h coSmuprovuinvdi.ng aInniimtaialls,ve7,re1ksaacnrdifi2c8ed and necropsied on day 28. FC95: Two doses vere used in the rangefinder study: 5,000 ms/ks aatndei1,t0h0e0r mdgo/ske.g. TNhoe dheiagthhesr odrosephalremvaeclotvoasxicchossigenns fwoerretheobsAelrlved study. FC-95 was applied as a suspension in water at 5,000 mg/kg. pHreyerpcieoorvdae.cretdivWiebtyiyghdwtaaysg7unnoastneddverreienmaio5n/b1es0dervameasdlyemsfpotoronmlasylilcatrtahbdrbaoiytusg6.h.outNAlolthveiasniisbmtlaueldsy Teeions vere noted at necropsy. Analysis of day 1 and day 28 blood fluorine (total) levels showed: : Total , ppm Day 1 Day 28 Hale Female 03 10.2 . 0.9 128.0 hFCi-g9h5daepvpeeaalrsdosteos.be sFbUs-o05rbecdanthberoucgohnstihdeeresdkinprabucttic1sallnoytnotonx-itcoxiact dermally. ) 03728 TPw5aCa2-nt09ge08ra0:.rimngdTN/ewvorogphdsdoaoosrusedmeysa.,cvoats5of,xhu0ies0ce0dc.oasnmidpgonNuso1n,vd0pe0hvr0aaersmmagnco/dotkoetgsdoe.wxdeirc8esInsauistgehnsdesuspvifeenunrlesltihoesonbtsuedirynvetdh.e Onneecrofpeemyaslemodigerdosuss alesrieosnusltsweroef amotteedcshniBclioaondhafnlduloirnigneerlreovre.ls Ab Total F, ppm Male Female Day 1 aio 226.14 Day 28 oh3 93.1 FapCcr-ua9tc8etiacdpaeplremlaayrlsnLotDnsosotobexiiscabgsrdoeerarbtmeaedlrlyat.nhdanel5img/iknga.tedFCto-9s8omceanexbteencto.nsiTdheered 050-0009-:, 20T0a0r-eeanddose1s00w0erneg/kues.ed ilno aadvrearnsgeefisingdnesr vsetruedysefeonr FatO-9a9n,y d$ao0is2ge9n9itlie1cvaealna.t lirTqehuaeicdti5oa,nn0sd00 voamrsg/pahkpagpmlmdisoecsodetowuxanisdciluussteiedgdnsintwoettrhheee fnoustkleildn..studNTyoh.ere VGehrseervnoabldeeatlhees.ionsWeivgehrte gnaoitneds.verTeotanlormballo.od Aftlunoercirnoepslyevneols vere: Total F, ppm Dayl Day28 Yale Female 29.0 735 2.5 11.5 toCx-i9c9 aepfpfeeactrse.d toThehavaecutbeeendersmlailghtLlDygabissorgbreedatweirthtohuetn a5ppg/akrge:nt F099 is considered practically nonztoxic dermally. FC-128: Three dose levels were used on the rangefinder, 5,000-, 2,000- and 1,000 mg/kg with O/k, 1/l, and O/k deaths respectively. BTseoucvsaepluesnesfiooronfthtiehnevfaudtleelart.shtuadtNyo.2,p0hT0ah0remmagcmo/atktogexriiicetlvsawisagsnscehpvopeslreienedaosbassetrhve&edd.oseThere wvTeeorrmeealennsootedldeoasttahtsw.eniegchrWtoepisgoyhv.tergatBihlneosodsvteufrdleyuornpieonrteieoddl.einvelNalsol vvmeiarseli:ebslebultes3i/o1n0s 03729 ot7a,plon bari payed Males Females 1.6 10.5 Lob 16.5 FatC-122,800a0ppnega/rkgs. to Tbhee arceultaetivdeelrymalpooLrDlsyo aisbsogrrbeeadtearntdhaisn 2nogn/-ktgo.xic FC-129: hres dose levels vere used in the rangefinder, 5,000-, 2vT",aip0urod0iey0ec.-tiyvan"oiTdfthey1p.,sh0aa0tr0eFmricivmoeegt/lokfxgvei.amcsalaeTsphipegclnais5bs:,bd0i0eu0lnedmtdighila/eurkdtggeyvd,id.tohspeirTnohwsae3rsaddtuaoiyssoseendoeaflinindcdtiohtseeidngf.aull rOFreaevteeamlarel,de pdai"Itcnedgeamnofettreeairle,d2 ldsaiuyvrsev.risvoraNsnedosrbohlpoosvioeeddsninooftlhteehcoisouenrsindeaytinignnetcahrceouptseyly(one Favbis had an' atrophic spleen). Blood Fluorine levels verer Tota 7, pon Day 1 Day 28 Fveatmete wwhi o6eds VGGlirovoeednafthlLbeusoroibnv(eifoeulmsealveetlosxriacbabriertessn)poton1smser5toigfc/uktlgha.orsieyFaonrriemvmaealalsleisntgoi.tFUl-To1h2eg9raectauhtteeer than 5 g/ig. F019 can be considered slightly toric dermally. TTFaCob-o1r31.k7:000hTehngrs/ekegv.edroeseTshneovemdraeevateuhrssieadloFvianPsMtAhuFepEpAiCrOiaLenOdgXeIf4Cisndsaeirgs:nuasp5Ae,t0n0s0ai-no,yn 2id,ons0e0.0- TSTneaecnugre1rtei1dndae$srtd4nyo rupeohmeaidrtmatchoeofto&3r,it0c0e0chsinhgiancksieavnearphepalnidoclbasitenirgvoened.r:rorA.sOnevietdihegahttthhe gains vHeerceropneoyt.es tBloorodalflaunoirmianles.leveMlos:vieible lesions were noted a Tota 7, pom byl Day es FMeamlaeises oe18.8 2138.a9 FC-134 seems poorly absorbed through the skin. The acute dercal Ibo is greater than 5 g/kg FC-13h can be considered non-toxic 03730 dermally. FC-135: Three dose levels were used in the rangefinder, 5,000-, 2GiZe,ana0kt0.sh0o-vaavTsnoedrpeuhs1ae,srde0pe0an0i.cnomtgt/ohWkxeegii.cgfhutlslTihggenaseitunmwisayet.revereireaoKlobsnweoparthsveeedrdampefpacotloriteoaadxnliylcundfodsesiimegla.nulsteesdo5,fa0ntd0o0the 8df/eo1cs0rionpmgaslyaensdn.ofvaiTiwsloiedblmeatloelsegsaiilononsstbawcwekeirgtehototbhsdeeurirvirendgi.ntihteiBallofoivrdestlfglhwuteo.erkineaAfttleervels Total F, ppm Dey l Day 28 Male 2.3 7.6 Female 6.9 20.8 Fd0e-r1m3a5l dseseoms irselgarteiavteelrytphoaonrl5yga/kbgs.orbeFdO-d1e3r5maclalny.be Tchoensiadceurteed practically non-toxic dersally. WAtotmaicehrments 03731