Document 6VX82E56Enyen4XGQm9eEgw4

CorporateHealth Physics CorporateOccupationalMedicine CorporateProduct Responsibffity Corporate Toxicology 3M Medical Department 3M Center,220-2E-02 PO Box 33220 St.Paul,MN 55133-3220 651733 1110 IdentificatioonfFluorochemicals in Sera of Children inthe United States The objectiveofthisstudy isto determineina sample of childrentheirseralevelsof perfluorooctanesulfona(tPeFOS), perfluorooctanoat(ePFOA), perfluorohexanesulfonate, N-ethylperfluorooctanesulfonamidoaceta(tJe?FOSAA), N-methyl perfluorooctanesulfonamidoaceta(tMe570), perfluorooetanesulfonamidoaceta(tMe556), and perfluorooctanesulfonamid(ePFOSA). In cooperationwiththeUniversityof NfinnesotaDepartment ofPediatricss,amples willbe obtainedthatrepresentserafrom 1,131 children(ages2 to 12 years)from 23 statesinthe United States.The serawere collectedas partof a largeclinicatlriarlegardinggroup A streptococcailnfectionsA. totalof 599 samples willbe tested.Seralevelswillbe compared to the childrens'age, gender and stateof residence.The timelineforstudycompletion,estimatedatJanuary 1, 2001, isentirelydependent upon a validatedanalyticamlethod to analyze0.1 ml of human serum forthesefluorochemicalswith a lower limitofquantitatioonf < 10 ppb based on high performance liquidchromatography electrospraytandem mass spectrometrymethods. CorporatOeccupationMaeldicinSeection/EpidemioUlnoigty Proposal March 16,2000 Tide:IdentificaotfiFolnuorochemicianlSseraofChildreinntheUnitedStates Purpose: Evidencethatorganiccompounds containingtheelementfluorinechemically bonded tocarbon canbe found inhuman blood was reportedintheliteraturmeore than 30 yearsago.Average serum perfluorooctanesulfon(aPtFeOS) levelsmay be withinthe 20 to 60 ppb range inthegeneralpopulation.Thisisprimarilbyased on pooledserum samples;thusitisdifficutlotascribefindingtsoany specifidcemographicgroup. The purposeofthisstudyisto determinethelevelof severalfluorochemicalfsrom the seraof children(2 - 12 yearsof age)intheUnitedStates. Signiricance:Determinationoftheserum concentrationosf selectedfluorochemicals willprovidefora more specifiucnderstandingofthedistributiofnthesecompounds in children.These datashouldbe helpfulintheriskcharacterizatipornocess. Objectives:The objectivoef thisstudyisto determineina sample of childrentheirsera levelsof perfluorooctanesulfon(aPtFeOS),perfluorooctanoa(t.ePFOA), perfluorohexanesulfonaNt-ee,thylperfluorooctanesulfonamidoace(tPaFtOeSAA), Nmethylperfluorooctanesulfonamidoacet(aMt5e70),perfluorooctanesulfonamidoacetate (M556), and perfluorooctanesulfonam(iPdFeOSA). Protocol:The Departmentof PediatricasttheUniversityof MinnesotaMedical School has storedserafrom 1,131 children(ages2 to 12 years)from 23 statesintheUnited States.The serawere collecteads partof a largeclinicatlriarlegardinggroup A streptococccailnfections[.SeePediatric1s998;101:86-88.]Serawere obtainedbetween January1994 and March 1995. These childrenpresentedwith signsand symptoms of acute-onseptharyngitisA.llofthe 1,131 childrenhad positivtehroatcultureastthe initiavlisit.Serahave been keptfrozenat-200C.At 3Ms requestt,heDepartmentof Pediatrichsasagreedto provide3M up to 0.1 ml perindividualA.n initiaplilotsample was conductedto determinewhetherthepresenceor absenceof fluorochemicalcsan be determinedwith0.1 ml serum. These findingssuggestedthatmethod validatiosnhould proceed. Because we areuncertainofthepopulationdistributioint,ispossibleto calculatseample sizebased on tolerancleimitswhich areindependentof theform ofthe distributioHno.wever, thetolerancelimitwsillbe widerthana parametricdistribution (NatrellMaG. ExperimentalStatistiNcesw York:Wiley& Sons,1966). For example, thelargestobservationina sample of45 individualosf a given age and genderwillbe an upper limiton 95% ofthatspecifipcopulatiownith confidencelevel0.90. Inthis particulasrtudy,the sample sizewillbe limitedby thenumber of samples,especialliyn theyoungestage ranges.On theotherhand,theuse ofbootstrapmethods willallowfor some smoothingof datatherebyincreasintgheprecisionoftolerancelimitsand reducing thesample sizerequirements(personalcommunication,Dr. Timothy Church, biostatisticiUanni,v ofW. Thereforet,hefollowingsamplesareproposedtobe analyzedinthisstudy: Age Group 2 3 4 5 6 7 8 9 10 11 12 Total TotalN 27 51 81 122 146 161 131 135 109 87 81 1131 TotalSampled(%) 27(100) 51(100) 81(100) 100(82) 80(55) 60(37) 40(31) 40(30) 40(37) 40(46) 40A9) 599(53) For thoseages where thesample sizeislessthan 100%, we willobtainequalpercentages by gender. Age (birthdatewas notcollectedg)e,nderand stateofresidenceforeach sample willbe provided. Fluorochemicalsto be analyzedarePFOS, PFOA, PFHS, PFOSAA, M570, M556 and PFOSA. Priortothisstudyproceeding,theremust be a validatedmethod to analyzefor thesefluorochemicalisn0.1 ml of human serum usinghighperformanceliquid chromatography electrospratyandem mass spectrometrymethods.The validated analyticamlethod shouldhave a lowerlimitof quantitationf < 10 ppb.Thisvalidated procedure be performedby NorthwestBioanalyticawlith technicaalssistancferom the3M EnvironmentalLaboratory. PMocation/cost: Geary Olsenwillbe theprincipailnvestigatorn thisproject.Dr. Timothy Church (AssociateProfessorU,niversityofMinnesota DivisionofOccupational and EnvironmentalHealth)willserveas thebiostatisticiJaena.nBurris,Dr. KrisHansen, Dr. JeffMandel and Dr. LarryZobelwillserveas 3M co-investigatorTso.talestimated costof thestudyis$250,000. Timeline: The timelineforstudycompletionisentireldyependentupon a validated analyticamlethod to analyze0.1 ml of human serum forthesefluorochemicalwsithan LLOQ of < 10 ppb. Ifsucha method isvalidatedby June 2000,thenitisestimatedthat thesample analyseswillbe completedby latesummer. Statisticaanlalysesofthedata shouldthenbe completedby OctoberI" witha draftfinalreportwrittenby November 15,2000. Review and approvalmay takean additiona4l5 days.Therefore,a final reportisestimatedto be availablbey January1,2001. A finalreportwillbe delayed shouldthevalidatioonf theanalyticamlethod takelongerthanexpected.