Document 935eN8qkyn8aZm0obLqkonzxV

CorporatHeealthPhysics 3M Center2,20-2E-02 CorporatOeccupationMaeldicine PO Box 33220 CorporatPeroductResponsibility St.PaidM,N 55133-3220 CorporatTeoxicology 6517331110 3M MedicalDepartment SerumFluorochemictarlendsofout-of-counrteysidenitnsCLUE 1(1974a)nd CLUE ][([1989e)pidemiologiincvestigations. This projectisa jointcollaborationbetween 3M and Johns Hopkins UniversitySchool of PublicHealthresearchersT.he objectivoef thisstudyisto analyze358 adultsera samplesthatwere collecteidn 1974 and 1989 as partof the CLUE I and CLLTE IIIstudies conductedinWashington County,Maryland. The serasamplesrepresentout-of-county residentwsho participateidnthestudy.A totalof 59 samplesarefrom individualwsho donatedinboth 1974 and 1989. An additionatlotalof 120 sampleswillbe analyzedin each yearof differenitndividualsF.luorochemicalsto be measured include perfluorooctanesulfonate(PFOS), perfluorooctanoate(PFOA), perfluorohexanesulfonate, N-ethyl perfluorooctanesulfonamidoacetate(PFOSAA), N-methyl perfluorooctanesulfonamidoacetate(M570), perfluorooctanesulfonamidoacetate(m556), and perfluorooctanesulfonamide (PFOSA). The titnelinefor study completion, estimated at January 1,2001, isentirelydependent upon a validated analyticalmethod to analyze I ml of human serum forthese fluorochemicals with a lower limitof quantitationof < 10 ppb, based on high performance liquidchromatography electrospraytandem mass spectrometry methods. TITLE OF RESEARCH PROPOSAL Serum fluorochemicaltrendsof out-of-countyresidents CLUE 1(1974)and CLUE 11(1989)epidemiolo0aicinvest0iaations I. RESEARCH OUESTION: Are fluorocheniicaldsetectablientheserum samplesofindividualwsho donatedblood to a coffimunity-basesdpecimen bank in 1974 and 1989 and to what extentdo levelschange overtime? 2. RATIONALE/BACKGROUND: The 3M Company (sponsorof thisproposal)manufactures widely-used productsthatcontainfluorochemicalFsl.uorocheniicaltsransformmetabolicalltyo perfluorooctanseulfonate(PFOS) as an endstagemetaboliteP.FOS isa surfactant and used in industriaalnd commercialprocesses.PFOS concentrateisnthe liverand undergoesenterohepaticirculationS.ubchronicstudiesinratsand primatessuggest a cumulativetoxicityresultinignloweredserum totalcholesterollevelsand metabolicwasting.Tlese effectmsay be due to effectson fattyacidtransport, metabolism,membrane functionsa,nd peroxisome proliferation. Exposure ratesto thesechemicalsamong thegeneralpopulationareunknown. Occupationallyexposed individualhsave been monitoredforthepresenceof fluorochemical(sOlsenetal).Among male productionemployees themean levels ofperfluorooctanseulfonat(ePFOS) in 1995 and 1997were 2.19ppm and 1.75ppn2, respectivelyN.o substantiaclhangesinserum hepaticenzymes,cholestemi,or lipoproteilnevelswere notedamong individualwsithlevelslessthan6 ppm. Only 7 individualisn 1995 and 5 in 1997 had levelsin excessof 6 ppm; no marked changes inlipidorhepaticenzymes were noted.Itisunknown towhat extenttheselevels can be detectedin thegeneralpopulation.This proposalisan exploratorystudy to determineforthe firstimewhethersenun concentrationosffluorochemicalasmong a non-occupationallyexposed populationincreaseovertimeand -whether concentrationvsary by genderor age. 3. METHODS From August through November, 1974, the Campaign againstCancer and Strokewas conducted inWashingtonCounty,MD. ReferredtoasCLUE I(from the slogan,"Give us a Clue toCancer"),a totalof 25,802personsdonatedblood,of whom 20,305 were countyresidentsT.he briefhistoryform was completedatthe time ofbloodcollection(Appendix1).The Campaign againstCancerand Heart Disease(CLUE H) was similartoCLUE Iinmost respects.Itwas conductedfrom May throughOctober,1989. Briefhistorie(sAppendix 1)andbloodpressureswere taken,and 20 rnlof blood were drawn. Participantwsere givenafood frequency questionnair(eAppendix 1)tocompleteathome and were askedtoreturnitwith a toenaicllippingfor tracemetalassays.A totalof 32,898personsparticipate(dtable For thisprojectwe willuse specimensfrom participantwsho arenot Washington County residentasnd who, thereforea,renot intheanalyticohort. These individualasrereferretdoasthe"out-of-countyg"roup. A totalof358 sampleswillbe selectedforassays(seetable1). Fifty-niniendividualisnthe '.out-of-countgyr"oup gave bloodsamples in 1974 and 1989. The age distribution of these59 individualsin 1974 was as follows:age 25-44 years-28;age 45-64 years -20-,age 65+ years- 11. We willanalyzeallof thisgroup forserum fluorochen-iical levelstodeterminechange inconcentrationosvertimewithinindividualsA.n additionaslample of 120 individualfsrom CLUE Iand CLUE IIwillbe selected stratifibeyd gender and age. Table1. Demopraphic DistributioonfTotalNumber (N 358) ofSerum SamDles tobe Analyzed Same individualbsoth years(n= 59/yr) Females* Males* Number ofSublects 1974 1999 32 32 27 27 Differentindividualseach year (1974,1989) Females <40 yrs 40-60 yrs >60 yrs 20 20 20 20 20 20 Males <40 yrs 40-60 yrs >60 yrs 20 20 20 20 20 20 *Age in1989 isprovidedbelow (1974dataanddistributiboynageby genderwas notknown at thetime thisproposalwas written) Assuming thecorrelatiobnetween thetwo measurementsobtainedi-n 1974and 1989 is0.8. thesample sizeof 59 providesa statistipcoawler of85% todetecta 10% differencbeetween the two timeperiods. Assuming themean PFOS levelsintheage group <40,4G-60and >60 are25,30,and 36 ppb, respectivelya,nd thestandarddeviatioins12 ppb foreachgroup,we estimate120 samples(40in each age group)willprovidea statistipcoawler ofmore than95% todetecta 20% difference among agegroups.This sample sizewillalsoallowfora statistipcoawler of78% todetecta 20% differencbeetween two groups(eg.m,en and women). Assay Measurements NorthwestBioanalyticawlillanalyzeforup to8 serum organofluorocheff@c(ailnscluding PFOS) usinghighpressureliquidchromatography//electrosptraanydem mass spectrometry (HPLC/ESMSMS) and evaluateversusan extractecdurve.Becausegeneralpopulatiosnerum samplesmnge intheareaof thelowerlimitofquantitati(oLnLOQ) forPFOS thatiscurrently used by Northwest Bioanalyticals,amplesfrom thisstudywillnotbe analyzeduntiltheLLOQ forPFOS (31 ppb) atNorthwestBioanalyticaclan be reducedby approximatelyIorderof magnitude. This validatioenffortiscurrentluynderway. 4. RISKS/BENEFITS For the assessment of theproposedbiomarkers,dataand blood were collected previouslyin 1974 and/orin 1989 when thesubjectsvolunteeredtoparticipatiena campaign tocollectblood fora serum bank and signedan informed consent.We cannot conceiveof any potentiarliskatthistime exceptforpossiblebreachesof confidentiality. The proposed substancetobe measured have not been associatedwith adversehealth outcomes in humans. This studyisthefirssttepto determineifexposure(asmeasured by internadlose)has even occurredamong non-occupationalleyxposed individualsN.o informationwillbe giventoindividualSse.ra willbe assayedand analyzedwithout individuaildentifiers.Statisticdaaltawillbe presentedby groups,withoutindividual identifierAst.thispoint,thereisno individuablenefitand virtuallnyo individuarlisk. Protectionagainstunauthorizedaccesswillbe obtainedby keeping theforms and computer filesin rooms thatarelockedwhen notinuse,and ina wing of theHealth Department thatisalsolockedwhen notin use. Access totheserecordsareauthorizedonly forstudentse,mployees of theTrainingCenterand collaboratorosf approved studieswho have signeda confidentialiptlyedge. S. ONSENT Persons were recruitedin 1974 and in 1989. At the times of blood donation, participantssigneda generalconsentform, allowingtheirblood and datato be used for researchpurposes. For each ofthesecampaigns,theconsentform and historyform were approved by the School'sConunitteeon Human ResearchatitsJanuary,2000 meeting. 6. CONFIDENTL4LIW/INSURANCES Allpersons who arepermittedtohave accesstoourrecordsmust have a legitimate purposeand must signa pledgeof confidentialitRye.cords forthisstudythatcontain personalidentifierasrekeptinrooms thatarelockedwhen notinuse and in a wing of the HealthDepartment thatisalsokeptlockedwhen notinuse.This wing israrelyused by anyone otherthan employees of theTrainingCenteror HealthDepartment. Personal informationthatmight be consideredsensitivseuch asdateof lastmenstrualperiod,and use of oml contraceptiveosr hormones iscoded ina way thatcannotbe interpretewdithouta key. The key iskept in a differenrtoom from thefilesW.hen dataaretobe used outsideof theTrainingCenter,names and addressesareremoved. In more than36 yearsof the existenceof theTrainingCenter,we know of no breachofconfidentiality. The responsiblepersonsareDr.George W. Comstock,Directorof theTrainingCenter forPublicHealth Research,Ms. SandraC. Hoffman, Asst.Director(,301-791-3230)and Dr. Kathy J.Helzlsouer,Directorof theSpecimen Banks, 410-955-9727. 7. COLLABORAIIVE AGREEMENTS: This proposalisnot bindinguntila signedagreementisexecutedbetween the3M Company and Johns Hopkins University. 8. OTHER IRB APPROVALS N/A 9. SINGLE PROJECT ASSURANCE N/A 10.PUBLICATIONS Itis3M's intentto co-authorinformationwithJohnsHopkins Universityresearchers derivedfrom thisstudy. The detailosfthiswillbe outlinedintheprojectresearchcontract. Under thisagreement Johns Hopkins Universitywould retaitnherighttopublishinformation from thisstudysolelyforitsown teachingand researchpurposes. 11. PROPREETARY DATA Proprietariynformationwillbe addressedin thefmalagreemnt signedbetween the3M Company and Johns Hopkins University. 12.BUDGET ne budget forthework contributioonftheinvestigatofrrsomJohns Hopldns University isattached. Personnel(On-campus) Num Role on Pro] Kathy Helzlsouer Principalinvestigator Han-Yao Huang Co-investigator GloriaZepp Secretary TotalOn-Campus Personnel Ratefiw $1,000 500 200 T.OW* $30,000 45,000 18,000 $93,000 Personnel(Qff-campus) Sandra Hoffman Projectcoordinator ClaraKrumpe' LaboratoryTechnician JudithBolton Data manager TotalOff-Campus Personnel $ 400 300 250 $ 4,000 18,000 5,000 $ 27tOOO Serum Bank Maintenance Costs (Maintenance, electricity,replacements) Cost Per ParticipantSample $225.00 x 300 samples $ 67,500 Other Expenses Laboratorysupplies(specimentubes,pipettes) Computer Supplies Shippingcosts (FedEx. dryiceshippingcontainers) Total Other Expenses $225-00 200.00 150.00 $5 ToW Project Costs (Johns Hopkins University) Total isan estimateof time tocomplete work. $188,075 Travelcostsby Johns Hopkins Universitiynvestigatorwsillbe billedirectltyo3M. All otherresearchstudycosts(e.g.a,nalyticaclostsby NorthwestBioanalyticalw)illbe paid by 3M.