Document GmXEZoq70Yokx41gYqZOoOxjY

. AR226-01%0 To2uo079919 3M MEDICAL DEPARTMENT, CORPORATE TOXICOLOGY POSF PK Protocol for Study No. T-7098.1 PHARMACOKINETICSTUDYOFPOSFINRATS oR- Y Study Objective: `Theobjectiveofhis studyisto astshepeotesntisal for oral absorption, urinary and fecal clearance and biological persistenceofperfluorooctane sulfon] fluoride (POSF) in male `Sprague Dawleyratsafter asingleoral dose.ThePOSF comistphesotartuingmnaterdial forthesynthesisof awidevarietyof perfluorooctanesulfonate(PFO) basedmaterials. `Thepurpoofstheisstudyis tounderstand the rateofmetabolism ofPOtoSPFFOSbythe liver, This study will provide data for proper risk characterizationofPOSE. 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 room SB314 SaintPaul,MN 55133-3220 Study Director: Andrew M. Seacat, Ph.D. Sr. Research Toxicologist 3M Medical Dept. / Corporate Toxicology 3M Center, Building 220-2602 SaintPaul, 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 220-202 Saint Paul, MN 55133-3220 Ph 651-737-1374 FAX: 651-733-1773 ProposedStudy Timeline (Assuming EHS&Rapproval on Jan. 5*): In-LifeStartDate: January 11th, 1999 In-Life End Date: February Sth, 1999 Analytical Completion Date: March 22nd, 1999 Final Report Completion Date: April 19th, 1999 04423 To0u9r8s1 POSFPK Regulatory Compliance: Thisstudywill be performed in the 3M Strategic ToxicologyLaboratory under adefined protocolandclassifiedas a"Class BStudy"asexplainedinTOX SOP0950, Strategic Toxicology Lab GLP Program Procedure. TestMaterial: `DanHakes,ProductResponsibility Liaison 3M Chemicals Division,willfanishhigh- purity POSF. Identification: Name: Perfluorooctane Sulfonyl Fluoride Molecular Formula: To be provided. Lot Number:Thelotmumberswillbemaintainedintherawdata. Purity:Documentation will be kept in on file. Stabilit`yD:ocumentation will be kept on file. Storag"eUCpoonndrietcieoinpts,:testmaterialwillbestoredtightlysealedat room temperature. Characteristics: Informatioonnsynthesis methods, compositionorothercharacteristics that definethetestmaterialwill bekeptonfile. Animals: Species: Rat Strain: Sprague Dawley Source: Harlan Age at initiation of treatment: 6-8 weeks Weight at initiation of treatment: approximately 150-2508 Number and sex: 30 males `Table 1 - Dose Group [Group [Dose IN [Euthanasia | P*hRarmaaicnogtkrioneustpisc1S-t3udwiylolfbMeu5se6dcin oRatns, canod Tm-a7is09c9to.n1ta,roPnlhaatrnmilamcaoylksiinnesttiucdSitesudTy-o7f07F1X.2-, 845 in Rats. Identification: ear tagwithanimalnumberoruniquetailmark. AUA Number: 2154 04424 2 7o0v9o8s.e1 POSFPK HusbandHroyu:sing: "Threespecificrats fromgroups 3and 6willbehousedindividuallyin memettaabboolliissmmccaaggeess,ftohrepsoerrtaitosnwsilofltbheegsrtouudpyh(osueseeTdaibnlset2a).ndWarhdecnagneost.inAll otherrats willbegroup housedinstandardcages throughoutthestudy. Diet/WHaatrelra:n TekladLM-485 Mouse/Rat SteriizableDiet, suppblyHiareladn Ttehklrado,Muadgtihhseosontu,udWytI., and tapwaterwill be providedtoallrats ad libitum EnviroEnnmveinrto:nmentalcontrolsfortheanimalroom willbesettomaintain a otfermopomeariartpoeufrr7h2eou+ra3nFd, ah1um2ihdoituyrolfig3h0t/-d7a0r%k,cyaclmei.nimum of 10 exchanges Dose and DosingProcedures: MethodAosfinagdlmeinSimsgt/rkagtdioons/eDoofsePOpSreFpwairlaltbioena:dministeredviaoralgavagetorats ingroups4-6ondayzeroofthestudy.ThePOSEwill bepreparaesad g1r%i(nd1erm. g/Amvl)oluunmifeoorfm smusipseunsspieonnsiino2n%/kgTwbeoednyw8e0iugshitngwial1lb5emltissue satrdokmesiofntihetsotticseascurehgreraidtn.deRr peestel-befsoroeuefascoshlsiadpsmwpilleelbiesndprearswfno-riumepidowntihtnhe5 sAsiyngrlfeio5rmdnlosg/iknegg.bodyweight doseof2%Tween80will beadministered viaoralgavagetorats ingroups 1-3ondayzeroofthestudy. ObservofaAtniimaolsn: ClinicaElfaOcbihsearnnviwamiatdllilowbinieslr:lnebceogrodbessde.rvAeddddiatiiloynfaolrfminodritnaglsiwtyialnlbdemrorebciodridteydaasntdhneoytaarbele observed. Body WEeaicghhtasn:imalwillbeweighedimmediatelyprior to dosing,weeklythereafier `andimmedpriioratoteutehanlasiya. SpecimenCollection: FreUrqi(nuesaeneedTfnaebclcees2cy)o:llectionswillbemadeondays 1,2,4,14an29pdost dose. Necropsieswillbeperformedondays1, 4and 29postdose. 04425 3 Ta2-bScl hede ule DOSdaIyN0G|| Cdoallye1cPtiDo|n| Cdoallye2cPtiDo|n| dSawyi3tPcDoh| | Cdolalyec4tPioDn| Dy1PD| Swichto| metcages. | Switchio sc| regaages. regDcyag4ePsD. TnE 17 EE Jam sc. Jan2S| Jame Jn2 meStwciagcetsho.|| CoSlwleicttictohon Feb3 Feb7| Feb8| Feb switch o| calection metcages| Dy29PsoDc aaysPD an30 be To-v7o0978e.s1 POSFPK. MethodUorfineSapencdfiemceenswCoillllebcetcioonl:lectedfrom eachmetabolismcageatthe designated times.Theinitialvolumeofurinewillberecorded,thesidesof t`hweatuerriannedctolhleecftiniaolnavpoplaurmaetoufsuwriilnlebweiwlalbsehberdowuigthhtt1o0-2405mmildweiitohnaidzdeidtional dtehieodneisziegdnwaatteedtri.mDeasi,laynfiemcaelsswwielilgbhetweiultlhbaneirzeecdorbdyeCdOf;oraenadcghraonsismnaelc.rAotpsy apbedrofmorimneadl.sDourtraianngdnetcrranospfseyr,rbeldtooobdlo(=od6cmoll)lewcitlilobnetcuoblelsecwtietdhvoiuatthe a3n0tmiicnoaugtuelsaantt.roBolmootdesmapmerpalteusrwei,lalnbdetahlelocwleodtwtiolcllboetsfpournapdeorwinodinofa 15 to cenatt11r00xigffor u mignutees.Theserumwillbetransferrteod lraebmeolvedea1n.5ymrlemicmroafurgieetdubnbleoisodanncedlgclesn.tEraifcuhgseedargaasinaatm2w0il0pl0txhlegnteboe ftrraonzsefneirrnelditqouidasnietpraorgaetne.lLaibveelre,dpkoildynperyospaynldesnemuibcrcofuugtetfauabtnefarenodomfeluaacsshhanimal willberemoved,weighed,flashfrozeninliquidnitrogenandplaced indiintvolabieleddstuerilaesalmpllebaygs.The remaoifeanchdcaercarss willbeplacedin alabeledziplockbagandfrozen (-70 C)untilanalysis. SpecimeSnpeHcainmdelnisnwigl:ltemporarilybestoredin afreezersettomaintain -60to 80C. Formetaboliteanalysis,thesespecimenswil bepackedindry ice andshippetod: 004426 ` K3rMisEHnavnisreonn,mePnht.aDl. Technology and Safety Services 935 Bush Avenue St. Paul, MN 55133-3331 Ph: 612-778-6081, FAX: 612-778-6176. To-7o098m.1 POSF PK `The3MEnvironmental Laboratorywillmanagetheextractionandanalysis ofsera, liver,urine andfecesfortheparentcompound,POS,and its presumed metabolite, PFOS. All tissuesampleswillbe retained for possible future analysisoftotal organic fluorine (TOF)if deemed necessarybythe S`tupdyeDitrrheicftsoaron.alry3simMs.EAnlvlirreosnumletnstwaillLbaepbroovriadteodorfirotrysindcelsuisginoeneiwnotuhledfinal report. `aTnhaelnysuimsbaerre,atsyfpoelalonwdsd:ate ofcollectionofspecimensto be generatedfor Table 3 - Specimens `Specimens Gayl |day2 [day4 |day1s |day29| Total pdoosste p|doosste pdoosste ||pdoosste p|doosste [Sem [[ 10 T T o To 150 | [vee Jo[ToTT [30 | [Kidneys Joo| Tw[ o Tio 30 | [Suboutencousfat [10 Two | Jio [30 | [Corcass [10 TT Tio Tio {30 | [Ue T6 Te Te To Je [30 | [Feces 6 To T6 Jo Jo [30| DDaattaacAonlalleycstiesd:on tissu levelsof parent compound and identifible metabolites will be: analyzedfortoxicokineticparametersandforstatisticallysignificant differencesbetween groups using Students T-test and/or ANOVA. RDeanaespNonsiabilbitiebs: efanedAnldrdewSeacatwillberesponsiblefordosingtheanimals, collectingin-[fespecimens,performingthenecropsyand collecting andsendingtissue `samples for analysis. KrisHansen,3MEnvironmental, will be responsibleforanalytical analysis. Andrew Seacatwill draftfina reportandensurethereportreceivesappropriate 3M review before a final report is issued. 04427 s Signatures: [rd Lo DrSe.nior ReseSarecahcaTotxicologist Study Director DeAdavnannacpeod ToxicolM ogiSst Study Toxicologist Sponsor Representative Ln te To-7v058o.1 POSFPK Date Date 04428 5