Document GmjGz9Y4goLq38b8OX0vQD3Qq

CorporatHeealthPhysics 3M Center2,20-2E-02 CorporatoeccupationMaeldicine PO Box33220 CorporatPeroductResponsibility st.PaulM,N 55133-3220 CorporatTeoxicology 6517331110 3M MedicalDepartment IdentificatoifFolnuorochemicailnHsuman Tissue Theobjcetiovfethisstudyistodetermitnheeconcentratriaotnioisn,humans,oflivetro serum,livertobileand biletoserum forperfluorooctanesulfon(aPtFeOS). An applicatiofnorsecuringliverg,allbaldderb,ileand serum from donorswas approvedby theInternationIanlstitutfeortheAdvancement ofMedicine(ILAM). HAM isa nonprofitorganizatiownhose purposeistofaciliateheplacementofnon-transplantable human organsand tissuefsorbiomedicalresearchand education.Alltissuesareprocured withtheinformedconsentof thedonor orthedonor'snextofkin,inaccordancewiththe Uniform AnatomicalGiftAct. Donors may be from anywhere intheUnitedStatesand Canada. Itisestimatedtotakeapproximately1 yearto securetissuesfrom 12 donors.A finalreportshouldbe availablbey March 1,2001. CorporateOccupationalMedicine Section/EpidernioloUgnyit ProposaltoEHS&R Committee 3/l/98 Title:IdentificatoifoFnluorochemicalisnHuman Tissue Purpose: Evidence thatorganiccompounds containingtheelementfluorinechemically bonded to carbon can be found inhuman blood has been known formore than30 years. Withinthepast12 months itwas estimatedthatserum PFOS (perfluorooctanseulfonate) levelsarewithinthe20 to 50 ppb rangeinthegeneralpopulation.Thisisprimarilybased on pooledserum samples. AlthoughPFOS isknown toconcentratientheliverand to undergo enterohepaticirculatiowne, do notknow what tissueconcentrationmsay be among humans. The purposeofthisstudyisto determinethelevelof several fluorochemicalfsrom theserum,liverand bileofthesame individua(lhuman). Signiricance:Determinationof thetissueconcentrationosf selectedfluorochemicalwsill providefora more specifiucnderstandingof thedistributioofnthesecompounds inthe human. The ratioof liverto serum,livertobileand bileto serum willbe compared to dataobtainedfrom studiesinnonhuman primates.Ultimatelyt,hesedatawillbe used in definingand confirmingassumptionsnecessaryinhuman healthriskassessment. Objectives:The objectivoefthisstudyistodeterminetheratioofliver:seruml,iver:bile and bile:serutmothefollowingfluorochemicalsP:FOS, PFOSA, PFOSAA, M570, M556, PFHS and POAA among 12 human donors.Totalorganicfluorinweillalsobe analyzedshouldanalyticamlethods permit. Protocol:An applicatiofnorsecuringliverg,allbladde(rbilea)nd serum from donors willbe submittedtotheInternationIanlstitutfeortheAdvancement ofMedicine(IIAM). IIAM isa non-profiotrganizatiownhose purposeisto facilitattheeplacementof nontransplantablheuman organsand tissuesforbiomedicalresearchand education.IIIAM is a divisionof thePennsylvaniaRegionalTissueand TransplantBank, an inspectedand accreditepdrogram which meets or exceedsallof theFood & Drug Administration (FDA) and theAmerican AssociatioonfTissueBanks standards.Alltissueasreprocured withthe informedconsentofthedonororthedonor'snext-of-kiinn,accordancewiththe Uniform AnatomicalGiftAct. Proofofdonorconsenttotheapplican(ti.e.3,NI)isnot alwayspossiblebecauseitmay involvethephotocopyingof privilegeidnformation. However, a donor identificatinounmber isprovidedtotheapplicantA. copy of a blank consentform isavailabluepon request.Donors may be from anywhere intheUnited Statesand Canada. AlldonorsaretestedforFHV, hepatitiBs, hepatitiCs, HTLV and syphilisI.IA.,Mprocuresand distributetsissueson an investigatorrequestbasis.The IIAM ApplicationReview Committee reviewseach applicatiofnorethicaclonsiderations, scientifimceritand feasibilitUyp.on approval,the3M requestisplacedintherotation forthetissueof interest1.1-AM abidesby U.S. legislatigoonverningtheconsentprocess fororgantissuedonation,theprotectioonf human subjecttshroughconfidentiality PageI of2 (HealtahndHuman Servic4e5sCFR PART 46)andTitlIenoftheNationaOlrgan TransplantAct,which prohibittshebuyingand sellinogf organsand tissuesexcluding reasonablereimbursementof expensesassociatedwith recoveryand placement Liverand serum analysesareplanned foranalyticaalnalysesusingmethods developed and/orapprovedby 3M's EnvironmentalLaboratory.The method forfluorochemical analysisofbileiscurrentlbyeingdevelopedin aEuropean laboratoruynder 3M's EnvironmentalLaboratoryguidance.A totalof 12donorswillbe obtained.HAM estimatesthattheywillsend 1 to 3 setsoftissue(liverg,allbladder/bialned serum)to 3M on a monthlybasis.Totalquantityper donationis:liver(10 grams);gallbladder/bile (intacta)n;d serum (5to 10 cc). PI/location/cosGte:aryOlsenwillbe thePI on thisprojectJ.eanBurrisand Jeff Mandel areco-investigatorKsr.isHansen willserveas thecontactwithinthe3M EnvironmentalLaboratory.Itiscurrentleyxpectedthatthe serum analyseswillbe conductedby NorthwestLaboratory.The 3M EnvironmentalLaboratorywillconductthe liveranalyses.A European laboratorcyurrentlvyalidatinagmethod forfluorochemical determinatioinnthebileofprimateswilllikelyextendthisvalidatiotnohuman bile. Approximatetotalcostperdonor is$1665. The distributioofnthiscostisthefollowing: shippingofsample $50;obtainingsamplefrom IIAM $710 (liver1,0 grams,$120; gallbladder/bilien,tact$,545;serum,5 to 10 cc,$50);tissuefluorochemicaalnalysis $900 (live$r300;gallbladder/bi$l3e00;serum $300). Totalcostfor12 donors:12x $1665 = $19,980. Thiscostdoesnotincludethevalidatioonffluorochemicalisnhuman bileby theEuropean Laboratory. Timeline: IIIAM estimatesthattissuefrom I to 3 donorspermonth can be providedto 3M. Thus,to obtainsamplesfrom 12 donorsmay takebetween 4 and 12 months. Due to theimmediate need tounderstandthisfluorochemicaldistributiownithinhuman tissues, sampleswillbe submittedforanalysisupon receiptby 3M. Ifthelastsample isobtained by theend of a sixmonth time frame,we estimatea finalreportof all12 donorscanbe completedwithin90 daysafterreceiptofthelastdonor'stissue.The finalreportwill includethefluorochemicaltissueconcentrations/levedless,criptionosf theage,gender, raceand geographicalocation(statoer)ofthenonidentifiabdloenors,and pertinent medicalhistoryinformatiotnhatmay be suppliedby IIAM (e.g.c,auseofdeatk known liverdisease)ofthe donor. Page2 of2