Document e7DEwnGGeG59Nb84O4Yjyxn4E

CorporatHeealthPhysics 3M Center2,20-2E-02 CorporatOeccupationMaeldicine PO Box 33220 CorporatPeroductResponsibility St.PaulM,N 55133-3220 CorporatTeoxicology 6517331110 3M MedicalDepartment DeterminatioofnSerumFluorochemicLaelvelisnSumitomo3M Employees Ninety-fouSrumitomo3M employeesparticipaitneadvoluntarcyr,oss-sectiosnearlum fluorochemicalassessment.Three groups of employees were examined. Sagamihara Plantproductionemployees (n = 32)were involvedintheinspectioannd convertingof finishedgoods. Sagamihara Plantmanagement employees (n= 32) were involvedin primarilynon-productionwork activitiesT.okyo Head Officeemployees (n = 32) are generallynotoccupationally-exposetdofluorochemicals.Allbuttwo ofthe94 participantwsere mate employees. Among the Sagamihara Plantproductionemployees, thehighestserum perfluorooctanesulfona(tPeFOS), perfluorooctanoat(ePFOA) and perfluorohexanesulfonat(ePFHS) levelswere 0.628 ppm, 3.6 ppm and 0.117 ppm, respectively.Serum levelsforthe Sagamihara PlantManagement and Tokyo Head Officewere,on average,under 0.01 ppm (PFOS), 0.03 ppb (PFOA) and 0.025 ppm (PFHS)Serum levelsof PFOS forSaganiiharaPlantmanagement and Tokyo Head Office employees were similarto levelsseen ina smallgroup ofUS 3M Center employees who were not occupationallyexposed toPFOS. Serum PFOS levelsof Sagamihara Plant productionemployees were below thoseofworkers atthe 3M Antwerp and Decatur plants. PROTOCOL OccupationalMedicine,220-3W-05 Medical Department 3M Company St.Faul,MN 55144 Date: 9january 1999 Title: DETERMINATION OF SERUM FLUOROCHEMICAL LEVEIS 3M SUMITOMO EMFLOYEES Study ProtocolNumber: EPI-0008 StartDate: EstimatedDate of FinalReport: IRBApprovalDate: 1/20/99 IRBApproval Exempt Expedited PrincipalInvest@ptor. Co-investigators: jean Burris,R.N.,M.S.' John C. Schumpert,M.D., M.P.H.1 Geary Olsen,D.V.M.,Ph.D.' JeffreyMandel, M.D., M.P.H.' StudyDirector: JeffreyMandel,bLD., M.P.H.- Study Sponsor. 3M MedicalDepartment 3M Company 220-3W-05 SaintPaul,MN 55144 1. OccupationalMedicine,MedicalDepartment,3M Company, 220-3W-05, St. Paul,MN 55114 PROTOCOL FOR SERUM FLUOROCHEMICAL DETERMINATION IN 3M SUMITOMO EMPLOYEES ABSTRACT 3M manufactures productswhich containchemicalcompounds, eitheras intentional components or residualimpuritiest,hathave as a parentmolecule,perfluorooctane sulfonylfluoride(POSF).These compounds may be expectedto transformmetabolically, toan undetermined degree,toPFOS as an end-stagemetabolite.Another compound manufactured by 3M includesammonium perfluorooctanoat(ePFOA).These molecules entera number of product application(seg.,surfactantsf,ood packaging additives, polymers). 3M Sumitomo inJapan processesmany of thesecompounds intoproducts for distributioannd sale.Fluorochemicalapplicationasre alsoinvestigateidn 3M Sumitomo laboratories. The purpose of thisstudy isto measure serum fluorochemicallevelsin selected employees ofthe 3M Sumitomo population.The specificfluorochemicalstobe measured includeperfluorooctanoicacid(PFOA) and perfluorooctanesulfonate(PFOS). RESEARCH METHODS Approximately 110 employees willbe invitedtoparticipatien thisnon-randomized cross-sectionasltudy;allsubjectsare volunteers.Thirtyindividualasre involvedin the processingand formulationvariousforms ofpure fluorochemicalsintofinished productsfordistributiotnhroughoutAsia.Approximately20 individualasre actively involvedin laboratoryfluorochemicalresearch.Approximately 60 managerial employees,considered non-occupationallyexposed to fluorochemicalsw,illalsobe invitedtoparticipate. Informationconcerning respondents'age,gender, and occupationwillbe obtained from 3M Sumitomo Human Resourcesforreview with theserum fluorochemical results. The studydurationwillbe appr-oximateltyhrreweeks. Writteninforznedconsentwill be obtainedfrom allstudy subjectsinJapanese (Appendix A).Each subjectwillbe involvedforabout 15 - 20 minutesand willdonate two lO mL blood sample.Should any emvlovee com Plicationsariseas a consequence ofphlebotomy,physicians associatedwith 3M Sumitomo willtreatthem. . Once the blood samples are obtained,they willbe frozenindry iceand sentby 3M Center in SaintPaul viaFederalExpress.At the 3M CenterMedical Clinic,serum wfll be separatedby centrifugatioannd senttothe 3M Environmental Laboratoryfor analysis.Standard electrosprayHPLC MS/MS willbe used todetermine the fluorochemicalcontentof allserum samples.Serum willbe analyzedforthe presence and amount of PFOA and PFOS. Resultswillbe reported tothe PrincipalInvestigatorin partsper billion(ppb).The PrincipaIlnvestigatowrillinfonn 3M Sumitomo employees oftheiFrFOSand FFOA levelasfterresulatnsda brieefxplanatiaornebetranslatiendto Japanese. The PrincipaIlnvestigatowrillforwardtheresulttsotheappropriateCo-investigator forstatisticaanlalysis.Descriptivsetatistipcesrformed willincludegroup mean fluorochemicalleveland standarddeviationofthemean, and range ofserum fluorochemicallevels.CozTelatioannd regr-essioanalyseswillbe performed utilizing informationobtainedconcerningage,gender,and occupation. RESULTS A fornutlreportoftheresearchfindingsi,ncludingdataanalysisw,illbe submittedto the 3M Medical Directorand InstitutionRaelview Board atthe conclusionofthestudy. The protocolwfflbe amended onlywith approvalofthe 3M InstitutionRaelview Board. AFPENL)IXA - CONSENT FORM CONSEN'R FOIL%4FOR COLLECTION OF BLOOD FOR SERUM FIUOROCHEMICA LEVEL DFTERMINATION INTROL)UCTION You and your colleaguesare involvedin fluorochemicalproduction,research,or management at 3M Sumitomo. You are invitedtoparticipatien a researchstudybeing conducted by 3M Corporate OccupationalMedicine regardingfluorochemicalsY.our participatiownould involvedonatingtwo red-toppedtesttubesofblood.Your blood willonly be testedfortheamount PFOA, PFOS, and itsprecursorsitcontains;itwillnot be used to testfor any other substancesor disease.Pleasereview thisconsent form carefullyand be sure your questionsare answered beforeyou make a decisionto participateA. 3M Sumitomo representativweillbe availabletoprovideyou with additionalinformationatthetime ofyour blood donation. PURPOSE OF STUDY The purpose of the study istodeterminethepresence and amount ofperfluorooctanoic acid(PFOA),perfluorooctanesulfonatea,nd itsprecursorsinyour serum. STUDY PROCEDURES Your blood willbe drawn with one needlestickand requiretwo testtubes.Illiswillbe a one-timeblood donation. POTENTIAL RISKS/BENEFrrS The risksof venipunctureincludepainon needleinsertionb,leedingunder the skin, discoloratiofnrom bleeding under thesldn,and discomfortfrom blood clotfir@g (hematoma) ifbleedingunder thesidnoccurs. BENEFITS There willbe no directbenefitfrom your participatioinn thisstudy. However, the informationgained from thisstudywillfurtherhelp us understandhuman exposuresto fluorochemicals.Your individualresultass wellas theoveraffresultswfflbe communicated to you only. Your individualresultswillbe consideredconfidential inforznatioannd wfllnot be disclosedto anyone outsidethe 3M Medical Department without your wtittenconsent. COMPENSANON No financialcompensation willbe forthcomingasa resultofparticipatinign thisstudy. Ifyou sufferinjuryor a medicalcondition'thaatppears tobe the resultof participating in thisstudy,you willbe refertedtoanother healthcare professionaaltno costtoyou. In the eventof a researchrelatedinjury,compensation willbe determined on a caseby case basisby 3M. CONFIDENTIALITY The overallresultscollectedin thisstudymay be used in publicationsor public presentation.Your name willnotbe revealedinany publicationor otherdocuments intendedforpublicationexamination.Your individualresultswillbe communicated to you only.Your individualresultwsillbe consideredconfidentiailnformationand will not be disclosedto anyone outsidethe3M Medical Department without your written consent. SUB-IJECTRIGHTS/AVAILABILnY OF INFORMATION Ifyou have any questionsabout thestudynow, or latero,r inthe eventof a research relatedinjuryor emergency, contactDr.JeffreyMandel (651-733-8670) orjean Burris,R.N.(651-737-7867). Foranswers toquestionsaboutyour rightsin regard to thisresear-chy,ou may contactDr. LarryZobel,Chair,3M InstitutionaRleview Board at 651-733-5181. VOLUNTARY PARnCIPAnON AND WRMDRAWAL Participatioinn thisstudyisvoluntary.Refusaltoparticipatweillinvolveno penaltyof lossof benefittsowhich you are otherwiseentitledY.ou are freeto refusetoparticipate forany reason.The investigatomray stopyour participatioinn thisstudyshould itbe determined thatcontinued participatiomnay be detrimentaltoyour health. SUBJECT CONSENT By signingtheconsent form, IcertifythatI am atleast18 years old. I confn-rnthatI have read thisconsent forzn,and thatI have been given adequate opportunitytoask any questionsImay have about thisconsentform or thestudy. Ialsoconfm thatI understand thescope of my participatioinnthisstudy,and thataflofmy questions have been answerrd tomy satisfactioIn.am sign@ thisconsentform voluntarilya,nd Idesiretoparticipatien the study.I understandthatI willreceivea copy of thissigned consent fonn. I understand thatIwillnotreceiveany financialcompensation for participatinign thisstudy. Signature PrintedName Witness Date FinalReport Epidendology,220-3W-05 Medical Department 3M Company St.Paul,MN 55144 Date: September 3, 1999 Title:Determinationof Serum FluorochemicalLevelsinSumitomo 3M Employees Study StartDate:March, 1999 IRB Approval Date:January 20, 1999 PrincipalInvestigator: Co-Investigators: Jean Burris,RN, NTH' Geary W. Olsen,DVM, PhD' JeffreyH. Mandel, MD, NVH' John C. Schumpert,MD, NTH' Study Director: Study Sponsor. JeffreyH. Mandel MD, NDH 3M Medical Department 3M Company 220-3W-05 St.Paul,MN 55144 1. OccupationalMedicine,Medical Department,3M Company, 220-3W-05, St.Paul, MN 55114 Introduction 3M manufacturepsroductsw,hichcontaicnhemicalcompounds,eithearsintentional components or as manufacturingresidualsw,hich, have as a parentmolecule, perfluorooctanseulfonylfluoride(POSF). These compounds may be expectedto transformmetabolicallyt,o an undetermined degree,toPFOS as an end-stagemetabolite. Another compound manufactured by 3M includesammonium perfluorooctanoate (POAA). These compounds entera number of productapplication(se.g.s,urfactants, polymers,and food packaging additives). Sumitomo 3M inJapan processesmany of thesecompounds intoproductssuch as fire protectionproductsand surfaceprotectionproductsfordistributioannd sale.Other potentialfluorochemicalapplicationasrealsoinvestigateidnSumitomo 3M laboratories. Purpose The purpose of thisinvestigatiownas toestimatepotentialfluorochemicalexposure to Sumitomo 3M employees, usingthe serum component of blood as an exposure measure. Methods 94 Sumitomo 3M employees participateidna voluntary,cross-sectionalf,luorochemical serum measurement. Itisassumed thatserum fluorochemicalsmeasured represent occupationalexposures,althoughwe have not includedfluor-ochemicaalirmeasurements from the Sagamihara plantin thisassessment.Employees ranged inage from 31-67. These employees came from threejob exposure groups as describedin a personal communication with S.Yamana. These groups were definedas:Sagamihara Plant productionemployees (n=32)involvedin theinspectionand convertingof finished goods. These workers were alsoinvolvedwith compounding, usingchemicals made from POSF, and formulationofproductscontainingadditionaflluorochemicals.The next group includedSagamihara Plantmanagement employees (n=32) working primarily atthesame siteas the SagantiharaPlantproductionemployees. There was no regular handlingof fluorochemicalsintheirusualwork capacitiesT.he lastgroup included management employees from theTokyo Head Officewho are generallynot occupationalleyxposed to fluorochemical(sn=30). Allbuttwo ofthe94 participants were male employees. Each studyparticipandtonated two 10 cc tubesof blood. Blood was collectedbetween March 17 and 19, 1999. The blood was centrifugedtwicefor 15 minutes at3000 RPM immediatelyafterdrawing to obtainserum. The serum was shippedfrozentothe 3M Medical Clinicin St.Paul,Minnesota where itwas distributetdothe appropriate laboratoriefsoranalysis.Following analyses,individualwsere notifiedof theirresultsby confidentialletter. Laboratory Analysis Individualserum was analyzedforseven fluorochemicalcompounds usinghigh-pressure liquidchromatography electrospraytandem mass spectrometrymeasurement (LC/MS/MS). NorthwestBioanalytica(lNWB) SaltLake City,Utah analyzedfiveof the fluorochemicalcompounds. They analyzed the serum forperfluorooctanesulfonate (PFOS), perfluorooctanseulfonamide(PFOSA), n-ethylperfluomoctanesulfonamido acetate(PFOSAA), perfluorooctanoat(ePOAA), and perfluorohexanseulfonate(PFHS). NWB conductsallstudieswithintheguidelinesof theUS FDA Good Laboratory Practicet,he OECD Principlesof Good Laboratory Practiceand theJapanese NTHW Good LaboratoryPracticeStandardOrdinance forNonclinicalLaboratoryStudieson the Safetyof Drugs (OrdinanceNo. 21,PAB NotificatioNno. 424).The 3M Environmental Technology and ServicesLaboratoryanalyzedthe serum forperfluorooctanesulfonamido acetate(M556) and n-methylperfluorooctanseulfonamidoacetate(M570). Northwest Bioanalytical'vsalidatedLC/MS/MS provideda lower limitof quantitation (LLOQ) in partsper million(ppm) of0.0314(PFOS), 0.001(PFOSA), 0.00223 (PFOSAA), 0.00527 (POAA), and 0.00261(@FHS). 3M Environmental Technology & ServicesLaboratoryprovideda lower limitof quantitatio(nLLOQ) inpartsper million(ppm) forM556 thatrangedfrom 0.01-0.025 ppm, and M570 thatranged from 0.01-0.05ppm. Data Analysis Data were analyzed usingstandardstatisticsaolftwareprograms. Comparisons of arithmeticmeans was done usingstudent'sttest.A statisticalsliygnificandtifferencein one of the means was setatp = .05 or less. Results PFOS Table I summarizes the serum PFOS, POAA and PFHS valuesforthe Sumitomo 3M employees.Twenty-four PFOS valueswere reportedbelow the lower limitof quantitation (0.0314ppm). Twelve (38%) of 32 Sagamihara plantmanagement employees had values lessthan thelower limitof quantitatio(n<LJ-OQ). The range of PFOS fortheremaining 20 employees inthisgroup was 0.032-0.057ppm. Descriptivestatisticasnd t-testwsere calculatedusingtheLLOQ value(0.0314ppm) forthoseindividualwsho had values below theLLOQ Fortypercentof theTokyo Head Officeemployees had PFOS values<LLOQ. The range of measurable PFOS was 0.033-0.0967ppm fortheremainingemployees. The remainingstatistiwcesre calculatedusingtheLLOQ value(0.0314ppm). PFOS was quantifiablien all32 Sagamihara Productionemployees. The arithmeticmean valuewas 0.135 ppm (range:0.0475-0.628ppm) which was significantdliyfferen(tp<0.05)thanthe mean PFOS value foremployees inboth theTokyo Head Officeand Sagamihara Plant managers group. POAA As per Table I thelower limitof quantitatiofnorPOAA was 0.00527 ppm. Three ofthe 94 employees had a POAA valuereportedlessthan thelower limitof quantitationO.ne of theseemployees was from the Sagamihar@Plant management and two were from the Tokyo Head Office.The midpointbetween zero and theLLOQ was utilizeidn calculatintghe statisticfsorPOAA. The mean POAA valueforthe Sagamihara Productionemployees was 0.201 ppm thatwas significantldyifferen(tp<0.05)thanthe mean POAA valuesforthe Tokyo Head Officeand Sagamihara Plantmanagers group. PFHS As perTable I fourteenpercentof employees had PFHS valuesreported<LLOQ (0.00261 ppm). Ten were employees from theSagamihara plantmanagement group and threewere from theTokyo Head Office.The midpoint between zero and theLLOQ (0.0013ppm) was utilizedtocalculatteheunivariatsetatistifcosrtheSagamihara plant management group. The arithmeticmean valueforthisgroup was 0.00626 ppm with a rangeof 0.0027-0.0241ppm. Again,thearithmeticmean PFHS (0.020ppm) forthe Sagamihara Productionemployees was significantldyifferenthan theotherexposure groups(p<0.05). PFOSAA,PFOSA We chose not to statisticalalnyalyzePFOSAA and PFOSA because of the largenumber of employees who had serum valuesreportedbelow thelower limitof quantitation. Eighty-fourpercentof allSumitomo 3M employees had PFOSAA valuesreportedbelow the lower limitof quantitatio(n0.00223ppm). Fifteenof 94 employees had a PFOSAA valuereportedbetween 0.00247 and 0.0133 ppm. The lower lin-dotf quantitatiofnorPFOSA is0.001 ppm. Four of the94 employees had a detectablelevelof PFOSA. These valuesranged from 0.00241-0.0068ppm. M556, M570 We chose not to statisticalalnyalyzeM556 and M570 because of thelargenumber of employees who had serum valuesreportedbelow thelower limitof quantitationO.nly one Sumitomo 3M employee had a quantifiablleevelof M556 (0.0032ppm). Ninety-threepercentof allemployees had M570 valuesreportedbelow the lower limitof quantitationT.he average M570 valuefortheseven employees with quantifiablleevels of M570 was 0.007 ppm. The range was 0.00311-0.0144ppm. Discussion Ninety-fouSrumitomo3M employeesparticipatienad voluntarcyr,oss-sectiosnearlum fluorochemicalassessment.Thirty-twoemployees were identifieads Sagamihara Plant productionemployees involvedintheinspectionand convertingof finishedgoods,doing some compounding, usingchemicalsmade from POSF, and doing some formulationof productscontainingotherfluorochemicalsT.hirty-twoemployees were describedas Sagamihara Plantmanagement employees who work primarilyatthesame siteas the Sagamihara Plantproductionemployees. Finally3,0 management employees from the Tokyo Head Officewho arenotusuallyexposedtomanufacturedfluorochemicals participateidn the assessment. Employees describedas havingthehighestexposuretoPOSF chemistryhad PFOS levels threetimeshigherthanemployees inboth theSagamihara plantmanagement group and theTokyo Head Office.The mean serum PFOS levelforplantproductionemployees was 0.135 ppm (range:0.0475-0.628ppm) compared tomean PFOS valuesof0.0403 ppm (range:0.0319-0.0566ppm) forSagamihara Plantmanagement employees and mean PFOS of0.0523ppm (range0.033-0.0967ppm) forTokyo Head Officeemployees. Serum fluorochemicalevelsinSumitomo 3M employees can be compared to serum levelsr-ecentlmyeasured in3M employees occupationafleyxposed to fluorochemicalisn facilitioeustsideofJapan (Table2). Serum fluorochemicallevelswere measured in employees at3M DecaturAlabama aspartof an on goingmedicalmonitoringprogram in 1997. Since 1980 theDecaturplantistheprimarylocationof theproductionof certain fluorochen-iictahlastmay ultimatelbye measured intheserum as PFOS. Arithmetic mean serum PFOS levelsin 1997 were 1.96ppm (range0.10-9.93ppm).I Outsidethe UnitedStates3M manufacturesPFOS relatedmaterialsatitsAntwerp, Belgium facility. Arithmeticmean serum PFOS levelsinAntwerp employees in 1997 were 1.5ppm (range:0.1-4.8ppm). In 199.831 3M Centeremployees inSt.Paul,Minnesotawere testedforserum PFOS. Allwere corporatestaffordivisiomnanagers. None had worked influorochemical production.Employees rangedinage from 37-62 years.Arithmeticmean PFOS was 0.047ppm (range:0.028-0.096ppm). Both thearithmetimcean and range forthisgroup aresimilartothearithmeticmean and range PFOS oftheSagamihara Plantmanagement (mean--0.0403;range--0.0319-0.056a6n)d Tokyo Head Office(mean--0.0523; range--0.033-0.0967). Conclusion Ninety-fourSumitomo 3M employeesparticipateidn a voluntaryc,ross-sectionsaelrum fluorochemicalassessment.Serum levelswere highestforSagan-iiharParoduction employees. This isthesame group where thereispotentiaflorgreateroccupational fluorochemicalexposure,althoughindustriahlygienemeasurements were notpartof this assessment.Serum levelsofPFOS forSagamihara Plantmanagement and Tokyo Head Officeemployees were similartolevelsseenina smallgroup of US 3M Center employees who were notoccupationalleyxposedtoPFOS. PFOS levelsarewellbelow levelsfound in workersatplantsitewshere POSF chemistrieasreproduced (Decatur, Antwerp). None of theselevelswould be expectedtobe associatewdith healthproblems based on our currentunderstandingof thesecompounds. Table I Serum FluorochemicalLevelsinSumitomo 3M Employees SaganiiharaPlant Production Employees N=32 Sagandham Plant Management N=32 Tokyo Head OMce N=30 Mean Median Std Dev Range -Mean Median StdDev Range Mean Median StdDev Range PFOS (ppm) LLOQ=0.0314 0.135 0.0919 0.131 0.0475-0.628 0.0403 0.0385 0.0071 0.0319-0.0566 0.0523 0.046 0.0191 0.033-0.0967 POAA (ppm) PFHS (ppm) LLOQ--0.00527, LLOQ=0.00261 0.201 0.020 0.0496 0.010 0.6265 0.0283 0.0189-3.600 0.00287-0.117 0.0117 0.00626 0.0096 0.0047 0.0091r% 0.0054 0.00264-0.059 0.0027-0.0241 0.0126 0.0048 0.01195 0.0038 10.00618 10.003 0.00264-0.029 10.0013-0-016 Table 2 3M Center 1998 N=31 Mean Serum PFOS Leveh Decatur 1997 N=84 Antwerp 1997 N=65 Saganiihara Saganiihara Tokyo Head Production PlantMgmt Office N=32 N=32 N=30 Mean PFOS 0.047 1.96 1.48 0.135 0.0403 0.0523 (ppm) REFERENCES Olsen GW, Bunis JM, Mandel JH, Zobel LR. Serum perfluorooctanseulfonateand hepaticand lipidclinicaclhemistrytestsinfluorochemicaplroductionemployees. J Occup Env Med (1999,inpress).