Document pmj1m1QR4EyX729EdYDZ1Qy1d

bo226-0209 PTO7S0F9P1K. 3M MEDICAL DEPARTMENT, CORPORATE TOXICOLOGY Protocal for Study No. T-7098.1 4 PHARMACOKINETIC STUDY OF POSF IN RATS i Study Objective: "The objectiveofthis study is to assess the potential for oral absorption, urinary and fecal clearance and biological persistenceofperfluorooctane sulfonyl fluoride (POSF) in male Sprague Dawley rats after a single oral dose. The POSF compound is the starting material for the synthesisof a wide varietyofperfluorooctane sulfonate (PFOS) based materials `The purposeofthis study is to understand the rate of metabolismofPOSF to PFOS by the liver. This study will provide data for proper risk characterizationofPOSF. Research Client: 3M Specialty Chemicals Division 3M Center, Building 236 Saint Paul, MN 55133-3220 Sponsor: 3M Specialty Chemicals Division 3M Center, Building 236 Saint Paul, MN 55133-3220 Study Location: 3M Strategic Toxicology Laboratory 3M Center, Building 270-35-06 roomSB314 Saint Paul, MN 55133-3220 Study Director: Andrew M. Seacat, Ph.D. Sr. Research Toxicologist 3M Medical Dept. / Corporate Toxicology 3M Center, Building 220-2E-02 Saint Paul, MN 55133-3220 Ph.: 651-575-3161 FAX: 651-733-1773 Study Toxicologist: Deanna Nabbefeld, MS Advanced Research Toxicologist 3M Medical Dept. / Corporate Toxicology 3M Center, Building 220-2E-02 Saint Paul, MN 55133-3220 Ph 651-737-1374 FAX: 651-733-1773 ProposeIdnS-tLiufdeyStTairmtelDiantee:(AJsasnuuamriyng11EthH,S1&9R99approval on Jan. 5%): In-Life End Date: February 9th, 1999 Analytical Completion Date: March 22nd, 1999 Final Report Completion Date: April 19th, 1999 00103 T0710079919 RTRrheiogstulosacttluodarynywdiClloambspeilfipieaerndfco5er:.med"CilnatshseB3SMtuSdtyr"ataesgiecxpTloxicology Laboratory undear dePfOiSneFdPK Toxicology Lab GLP Program Procedure. ained in TOX SOP 0950,Strategic TDeasntHMaatkeer,iaPlr:oduct purity POSF. Responsibly Liaison 3M Chemicals Divison, will furnishhigh- Identification: MNoalmeec:ulPaerrfFlouromruoloac:taTneoSbuelfpornoyvlidFeldu.oride Purity:Lot Number: The lot numbers wil be maintainedin the raw data. StabilitDy:ocumentation will be kept in on file. StorageDoCconudmietnitoantsi:on wil be kept on fle. `Upon receipt, temperature, test material will be stored tightly sealed at room Characdteeifrniifnsoterimtcahste:itoensotnmastyenrtihaelsiwsilmebtehokdesp,tocnomfpiolesition or other characteristics that , Animals: Species: Strain: Rat Sprague Dawley ASoguercaet:initiatiHoanorlfantreatment: 6-8 weeks Neuimgbhetraatnidnisteixa:tionof30trmeaaltemsent; approximately 150.2505 Table 1 - Dose Group Foow [Dose TN Thun LSPphaartmsacionokgironoeutpiscS1S-tm3udwyieollfebMe5u3s6ediTcnoRnsactso,miaanndil7y-7a0s99c.[o1n,trgPohluanipmatl inasedis 7071.2, 845 in Rats. armacotman Studyof FX- AMdUenAtiNfiucmabtieorn:: ~~ ear tag 2154 with animal number or unique tail mark. 000104 -- 2 Husbandry: To7v0o9719 POSFPK `Housing: mTmeehtteaabeboosllpiiesscmmifcciaacggaeetsssftfohrreospmeorgatrtioosunwspislolft3bhaeengdrs6touuwdpiylh(losbueeseehTdoaubislneesdt2)i.ndiWvhideunallnyotinin Diet/Waottehre:r rats will be group housed in standard cages througahndoaurtdtchaesgteusd,y.All tHchharerdolauadgn,hToMeuaktdltiahsdeoLns,Mtu-Wd4yI.8,5anMdoutsacp/wRaatterStweiililzbaebplreovDiidte,dstuoppalliredtbsayHearulanm EnviroEGnammpieetnrotan:tmuernetaolfc2ont+ro3lFsf,ohrtumhiediatnyiomfal3r0o-o70m%w,ilal be st to maintain a ofroomair per hourand a 12 hour light/dark cyclme.inimum of 10 exchanges Dose anMdetDhosoidnogfaPdrmoicneidsurtersa:tion/Dose preparation: 1i1h4%Bsir(no1gulmpesgS4mm-e)6/kougnndidafooysrzemoerfsuosPopOfeSntsFhieownisltilundby2e.9a%dTTmhiweneiPesOnteS8rEe0dwuivsliilanbgoeraaplrgeapvaargee atgo rats asgtdrirmnoidkneeirss.toefArtehdveotltoiuesmsaeucehogrrfaitn.mdieRres-puesssuptseepnlesbniesofinoo/rnkoegfcsbooldiydswweiiglhbteopielr1bf5eomrlmeednwuieth 5 syringe for dosing, ach sample isdrawnup in vsiinnograllegSavmalg/ektgo rbaosdyinwgeirgohutpsdo1s-e3oofn2da9yzTewreoeonf 8t0h wisltlubdye.administered ObservaCtliionniocaflAOnbismearlvsa:tions: fo{ibanscdehirnvagesndi.wmialll bweirlelcboerodbesde.rvAedddidtaiiloynaflorfimnodritnaglsitwyilalnbdemroercboirddietyyaasndthneoytaabrlee Body Weights: `Eaancdhimamneidmiaaltveillyl pbreiowretiogheeutdhianmamseida.iatlyprioto dosing, weekly thereater SpecimeFnreCqoulelnecctyio(ns:ee Table 2): dnosee. aNnedcrfoepcseisecsolwliellctbieonpsewriflolrbmeedmaodnedoanysda1,ys4 1a,n2d,245, p1o4standdos2e0 post 000105 -- 3 =7" |LeTabmlea2-E SchweE diulte 8]E BEE aEl]E AeoTrE =z A HE5B2 enlO | te o EHaz met cages [Dy 29 PD Methodof Specimen Collection: Urine and designated feces will be times. The collected from each metabolism cage at initial volumeofurine will be recorded, the wtahteeurrainnedcotlhleefcitniaolnvaoplpuamraetoufsurwiilnlebweilwlabsehebdrowuigthht 10-20mideiotnheizseiddesof deionized water. Daily feces the designated times, animals `weight will be to will be recorded euthanized 45 for ml with additional each animal, At performed. During abdominalaorta and necropsy, blood transferred (= 6 ml) by CO,andgrossnecropsy will be collected via the anticoagulant. 30 minutes Blood samples to will blood collection tubes without be allowed to clot foar period of15 to centrifuagteat1ro1 oxm gt0efmop0 reratmuirneu,teasn,d`tThheescleortuwmilwlibllebsepturnadnsofwenrrienda labeled remove 1a.n5ymrlem`amiincirnofgurgeedtubbleosodancedllcs.entEraicfuhgesderaagsaainmpalte2000 x gto to transferred to a frozenin liquid separate nitrogen. labeled Liver, polypropylene kidneys `microfugewitlulbethaenndbfelash- i`nadniivmialduwailllybientroelmaobveelded, swteeiriglheesda,mfpllaeshbfagraso.nzdenTshuinbeclruieqtumaiandiennodiutesrrofoagfteenfaraconhmd cepaalrcachcaesds will be placed in a labeled ziplock bag and frozen (-70 C) untilanalysis. Specimen Handling: a8Sn0pdeCcs.ihmiFepopnersdwmiteolt:labtoelmiptoeraarniallyysbise,stthoerseed sipneacfirmeeenzserwsiellt bteo pmaacinkteadinin6d0rytioce- 000106 : 3KrMisEHnavnisreonn,mePnht.aDl, Technology and Safety Services 935 Bush Avenue St. Ph: Paul, MN 55133-3331 612-778-6081, FAX: 612-778-6176, T0210079919 POSF PK poTrfhseeesr3uam,MeldEivnmeveri,taruboronilmnieetneat,nadPlFfLOeaScb.eosrfAaoltrtotrhiyesswupielalremnatncaogmeptohuendex,trPaOcStiFo,n aannddaniatslysis Sftutuudrye Dainraelcytsoirs.oft3oMtaElnovrigraonnimcenftluaolriLnaebos(arTmaOptFlo)ersyifdwoierlelftmbs eeddersenitegacineneesedsafroyrpboysstihbele rpeeprofrotrm his analysis. All results willbe providedfo inclusion iwnofualefdinal ahnaelynsuismbaerre,astyfpoellaonwsd:dateofcollectionofspecimens o be generated for Table 3 - Specimens `Specimens Pdoasyt 1 d[apoyst2 dose |dose fdpaoyst4 [dose [dpaoyst 15 | p[doays29 | Tota] |dose | dose fom oe ho To o 1 ioi e peep] ee tree [bene Tho Tio Tio] [Tip fom foe To de To TToo--T --o -- i 2] ] Fees le To To Te--fe--u--] Data Analysis: 8aD7na0atluaypczsoeuldlsfeiocnrtgetdSotxouindceotnkiitsnsseuTte-iltceevpsetalsaronafdmlpoearrteeanrtndscofmorpostuantidstaicnadlliydseingtniiffiiacbalnet.mdeitfafbeorleintceesswbielltwbeeen ANOVA. Responsibilities: scDaoelmalpnelcnetasinNfgoaribnbaleniaffleeylssdipseacnidmeAnnsd,rpeewrfSoeramciantgwtihlelbneecrreosppsoynsainbdlceolfloercdtoisnignagntdhesaennidmianlgs,tissue + rAKernvidisreHweawnbesSfeeonar,ceaa3tMfwiinlEalnlvdrirerapfootnrmatefniistnaaillss,rueewdpi.olrltbaenrdesepnosnusrieblteheforrepaonraltytrieccaelivaensalayspipsr.opriate 3M 000107 ---_ 5 Signatures: wd Dr. ffdrew Seacat - Senior Research Study Director Toxicologist Deanna Nabbefetd, Ms Advanced Toxicologist Study Toxicologist Po 97 SpomsorRepresentaive pm 7o0u98r.s1 POSF PK. d0o108 es - .