Document Rp2xZLJB6mNDa4xybn9d3YBOa

CorporateHealth Physics Corporate OccupationalMedicine Corporate ProductResponsibility Corporate Toxicology 3M MedicalDepartment 3M Center,220-2E-02 PO Box 33220 St Paul,MN 55133-3220 651733 1110 An Epidemiologic Investigationof ClinicalChemistries,Hematology and Hormones in Relation to Serum Levels of PerfluorooctaneSulfonateinMale Fluorochemical Production Employees Following reportsof the findingof organicfluorineinserasamples,a fluorochemical medical surveillancperogram began at3Ms Decatur manufacturingfacilitiynthe late 1970's.The surveillancperogram has generallyconsistedofannual or biannualtestsof clinicaclhemistriesp,ulmonary function,blood countsand a biomonitorof fluorochemicalexposure. A totalorganicfluorinemeasurement was routinelydone until 1993. This measures the amount of fluorinethatwas covalentlybound to carbon inthe serum sample. When testdatawere availablea, company physicianreviewed each employee'sresults.These physiciansdid not and have not,found abnormalitiesin individualtshatthey feltwere relatedtofluorochemicalexposure. That is,medical conditions,medicationsand lifestylfeactorsadequatelyexplainedthe laboratory abnormalitie(swhich one expectstofindinthistype of program.) Beginning in 1994,the3M Decatur (Alabama) plantmedical surveillancperogram incorporateda serum measurement of perfluorooctanesulfonate(PFOS) and perfluorooctanoat(ePFOA). Totalorganicfluorinewas notmeasured. A formalreport was writtenof theaggregateanalysesconducted of themedical surveillanccelinical program datafortheDecatur (Alabama) and Antwerp (Belgium)employees who voluntarilpyarticipateidn 1994,@1995and 1997. The findingsfrom thisaggregate analysissuggestedthat,among theseparticipatinAgntwerp and Decatur male fluorochemicalproductionemployees, significanhtematological,clinicaclhemistryand hormonal abnormalitieswere not associatedwith serum PFOS levelsup to 6 ppm. Itwas not possibleto deriveinferencesfrom the few employees with serum PFOS levels> 6 ppm. Limitationsofthisstudyincludeitscross-sectionadlesign,the voluntary participatiornates,the few subjectsexposed atthe highestlevels,and the lower levelsof serum PFOS measured among theseemployees compared to those estimatedto cause effectsinlaboratoryanimals. Resultsofthe hepaticand lipidclinicaclhemistrytests were publishedintheJournalof Occupationalcmd EnvironmentalMedicine (1999;41:799-806).In the Springof 2000, medicalsurveillancweillagainbe offeredto 3M fluorochemicalproductionemployees atthe Antwerp and Decatur manufacturing sites. April22, 1998 An EpidemiologicInvestigationf ClinicalChemistriesH,ematology and Hormones inRelationtoSerum Levelsof PerfluorooctanSeulfonateinMale FluorochemicalProductionEmployees Geary W. Olsen,D.V.M., Ph.D. JeanM. Burris,R.N.,M.P.H. JeffreyH. Mandel,M.D., M.P.H. LarryR. Zobel,M.D., M.P.H. MedicalDepartment,3M Company, 220-3W-05, St.Paul,MN 55144 PaL7e- ABSTRACT 3M manufacturesproductswhich containchemicalcompounds, eitheras intentionaclomponents or residualimpuritiest,hathave as a parentmolecule, perfluorooctanseulfonylfluoride.These chemicalsinclude:perfluorooctanseulfonate (PFOS),N-ethylperfluorooctanesulfonamiNd-ee,thylperfluorooctanesulfonarnido ethanol,N-methyl perfluoroctanesulfonamiedtohanoland chemicalsderivedfrom it,and themixtureofmono-, di-and tri[N-ethylperfluorooctanseulfonamidoethylp]hosphates. There may be otherprecursorsin theworkplace.These moleculesentera number of productapplication(se.g.s,urfactantfso,odpackagingadditivesp,olymers).These compounds may be expectedtotransformmetabolicallyt,oan undetermineddegree,to PFOS as an end-stagemetabolite.Potassiumperfluorooctanseulfonat(eC8Fl70SO2K@) is,itselfa,surfactanutsed asa wettingand foaming agentin industriaalnd commercial processes. Subchronicstudiesin ratsand primatessuggesttheremay be a potentiaflor cumulativetoxicitwyithPFOS overtimewiththeprimaryeffectrelatedtometabolic wasting. Althoughthemechanism oftoxicitiysnotfullyunderstoodt,oxicitmyay be due toan effecton peroxisome proliferatiofna,ttyacidmetabolism,membrane function, proteinsynthesisand/ormitochondriablioenergetics. Niedicalsurveillancheas been routinelpyerformedon 3M fluorochemical productionworkers(inDecatur,Alabama and Antwerp,Belgium)withpotentiaelxposure to PFOS and/ortoperfluorinatepdrecursorsthatmay metabolicalldyegradeto PFOS. The purposeof thisstudywas to providean analysisof thehematology(hematocrit, hemoglobin,redblood cellsw,hitebloodcellsand platelectount),clinicaclhemistries Page 2 (alkalinpehosphatase,gamma glutamyltransferasea,spartataeminotransferasea,lanine aminotransferaset,otaland directbilirubinb,lood ureanitrogenc,reatinineg,lucose, cholesterolo,w densitylipoproteinhsi,ghdensitylipoproteinasnd triglycerideasn)d hormonal parameters(cortisodle,hydroepiandrosteronseulfatee,stradioflo,llicle stimulatinhgormone, 17-alphahydroxyprogesteronel,uteinizinhgormone, prolactins,ex hormone bindingglobulin,freetestosteronbeo,und testosteronaen,d thyroidstimulating hormone) inrelatiotno serum PFOS as determinedby highperformanceliquid chromatography mass spectrometrymethods.These relationshipwsere assessedin fluorochemicaplroductionemployeesfrom two time periods,1995 (N = 178) and 1997 (N = 149). Descriptivesimple and stratifiaendalysesP,earsoncorrelatiocnoefficients, analysisof varianceand multivariablreegressionwere used toevaluateforpossible associationbsetween PFOS and each hematologicaland clinicaclhemistrytestand hormonal assay. Age, body mass index,currentalcoholconsumption(drinksper day) and cigarettuese (cigarettessmoked perday)were potentiaclonfoundingfactorsthat were consideredintheanalysesM.ultivariablreegressionmodels were fittewdith PFOS analyzedas a continuousvariableusinglinearas wellasnon-lineartransformationisn ordertomaximize thepossibilitoyf findingassociationbsetweenPFOS and the parametersof interest. Four categorizationosfserum PFOS levelswere assessedinrelatiotno the responsevariables0:- < I ppm; I -< 3 ppm; 3 - < 6 ppm; and > 6 ppm. In 1995,mean serum PFOS levelsby categorywere 0.49ppm, 1.82ppm, 4.12ppm and 8.17ppm, respectivelyI.n 1997, mean serum PFOS levelsby categorywere 0.52ppm, 1.78ppm, Page 3 3.87ppm and 7.20 ppm, respectivelyF.or bothyears,95 percentof theemployees' serum PFOS levelswere below 6 ppm. Although thetwo plantpopulationsdifferedby age,body mass index and alcoholconsumption,no consistenatssociationbsy, bothplant locationasnd year,were observedbetween theclinicaclhemistriesh,ematology and hormone parameters and theemployees'serum PFOS levels. The findingsfrom thisstudysuggestthat,among theseAntwerp and Decatur male fluorochemicaplroductionemployees,significanhtematologicalc,linicaclhemistryand hormonal abnormalitieasrenotassociatedwith serum PFOS levelsup to6 ppm. Itisnot possibletodeiiveinferencesfrom thefew employees withserum PFOS levels> 6 ppm. Limitationsof thisstudyincludeitscross-sectiondaelsign,thevoluntaryparticipation rates,thefew subjectsexposed atthehighestlevelsa,nd thelower levelsof serum PFOS measured among theseemployees compared tothosethatcausedeffectsinlaboratory animals. Page 4 INTRODUCTION 3M manufacturesproductswhich containchemicalcompounds, eitheras intentionaclomponents or residualimpuritiest,hathave as a parentmolecule, perfluorooctanseulfonylfluoride.These chemicalsinclude:perfluorooctanseulfonate (PFOS),N-ethylperfluorooctanesulfonamiNd-ee,thylperfluorooctanesulfonamido ethanol,N-methyl perfluoroctanesulfonamiedtohanoland chemicalsderivedfrom it,and themixtureof mono-, di-and tri[N-ethylperfluorooctanseulfonamidoethylp]hosphates. There may be otherprecursorsintheworkplace.These moleculesentera number of productapplication(se.g.s,urfactantfso,odpackagingadditivesp,olymers).These compounds can be expectedto be transformedmetabolicallyt,oan undetermineddegree, to PFOS as an end-stagemetabolite[Gibsonetal.,1983].Potassiumperfluorooctane sulfonat(eC8Fl70SO2K) is,itselfa,surfactanutsed asa wettingand foaming agentin industriaalnd commercial processes. Potassiumperfluorooctanseulfonatiesreadilyabsorbedby ingestion[Johnson and Ober,1979;O'Malley and Ebbens,19801. Ninetyfivepercentof a singleoraldose of [14C] PFOS administeredto male ratswas absorbedwithin24 hours [Johnsonand Ober, 1979]. Aftera single,24-houroccludeddermal exposuretoPFOS ata doseof 5000 mglkg,totalserum organicfluorinceoncentrationwsere 10.3and 0.9ppm formale and femalealbinorabbitsr,espectivel[yO'Malleyand Ebbens,19801. Twenty eightdays afterdosing,totalserum organicfluorinceoncentrationhsad risento 130.2and 128.0 ppm formale and femalealbinorabbitsr,espectivelyO.n theotherhand,no quantifiable Page 5 organicfluorinceould be detected28 daysaftera single2,4 hour occludeddermal exposuretoa 0.06% solutionof PFOS in wateratdoses of0,0.003,0.06,and 0.3mg PFOS solution/kgr,espectivelyt,o 3 male and 3 femalealbinorabbitsperdose group [Glaza,1995]. Once inthebody,PFOS concentratepsrimarilyintheliverof rats[Johnsonetal., 19791.Eighty-ninedaysaftera singleintravenoudsose (mean 4.2 mgtkg) of radiolabelePdFOS, mean tissueconcentration(sgg PFOS equivalent/tgissue)were: liver2,0.56;plasma,2.21;kidney,1.09;lung,1.06;spleen,0.51;bone marrow, 0.46;red blood cells0,.45;adrenals0,.41;testes0,.36;skin,0.35;muscle,0.29;subcutaneousfat, 0.20; eye,0.16;abdominalfat,< 0.08;and brain,< 0.05. Johnson etal.[1979]observed that30.2percentofthedose 89 daysafteradministratiohnad been excretedin theurine and 12.6percentinthefeces. Analysesof theurine,fecesand tissueshave suggested thatPFOS isnotmetabolized[Johnsonetal.,1984]. The plasma half-lifweas calculated to be 7.5days aftera singleoraldose ofradiolabelePdFOS (mean dose,4.2mg/kg) in solutiontothreemale rats[Johnsonand Ober, 1979]. There appearsto be significanetnterohepaticcirculatioonf PFOS with both urinaryand fecalexcretion[Johnsonetal.,1979;1980;1984].In male rats, cholestyramineadministeredin thefeeddecreasedtheretentioonf radiolabelePdFOS in liverp,lasma,and red blood cells3,.8,7.7and 6.0fold,respectivelya,nd increasedits eliminationviafeces9.5foldaftertheratswere given intravenousradiolabelePdFOS (mean dose,3.4mg/kg) [Johnsonetal.,1980;1984]. There was a lowerclearancerate of 14C intheurinecompared to controlanimals becauseof theincreasedrateof fecal elimination.Cholestyramineisa bileacidsequestrantthatactsby bindingbileacidsin Page 6 theintestinatlract.This reducesbileacidresorptioannd itsreturnto theliver.Decreased flow of bileacidsintheenterohepaticcirculatiornesultisnincreasedconversionof hepaticcholesteroilntobileacids.Thisresultisna declinein hepaticcholesterol concentratioannd thestimulatioonflow densitylipoprotei(nLDL) receptorsynthesis, which subsequentlyproducesa declinein serum LDL cholesterollevels. Upon acuteexposure,PFOS was moderatelytoxicby oraladministratio[nGabriel, 1976;Dean etal.,1978;Rusch and Rinehart,1979],butnotdermal [O'Maey and Ebbens, 1980]. There have been two acuteoraltoxicitsytudiesreported[Gabriel1,976; Dean etal.,1978]. In themore recentstudyPFOS was suspendedina 20% acetone/80% com oilmixtureand administeredorallyby gavage levelsto 5 male and 5 female ratsper group atthefollowingdosages:100,215,464 and 1000 mg/kg [Dean etal.,1978]. Animals were observedfor14 days.The acuteoralLD50 values(95% confidencelimits inparenthesesw)ere male rats2,33 (160-339) mgtkg;femalerats271 (200 -369)mg/kg; combined male and femalerats2;51 (199 -318) mgtkg. Clinicaslignsincludeddiarrhea, hypoactivityd,ecreasedlimb tone,ataxia,cornealopacityp,tosisp,iloerectiopnr,ostration and tremors. In thepreviousstudy,PFOS was administeredinwaterand theLD50 inthe ratwas determinedto be 1.25- 2.50g/kg [Gabriel1,976].Gabriel'sresultsappeartobe inconsistenwtithsubsequenttoxicitsytudies. In an acuteinhalatiotnoxicitsytudy[Rusch and Rinehart,1979],a seriesof onehour inhalatioenxposuresinratsatexposureconcentrationosf PFOS at24.09,7.05,6.49, 4.88,2.86,1.89and 0.0mg/L produced 100 percentmortalitayt.thehighestleveland partiamlortalit(y10 -80%) atallotherPFOS levels.Observationsincludeddyspnea, tremors,convulsionsh,ypersensitivihtyp,oactivitye,xcessivesalivatioannd laciimation Page 7 and generalpoor condition.The LC50 was determinedtobe 5.2mg/L (95% CI = 4.46.4mg/L). PFOS has been shown tobe a potentinducerof hepaticperoxisomesand fatty acidbeta-oxidatioinn therat[Ikedaetal.,1987]and mouse [Sohleniusetal.,1993]. Afterfeedingmale ratsfortwo weeks with a powdered chow containing0.02% PFOS, hepaticcatalasef,attyacyl-CoA,camitineacetyltransferasaend camitinepalmitoyl transferasiencreasedby 1.74,4.90,6.84and 1.69fold,respectivelcyo,mpared tocontrol animals[Ikedaetal.,1987].PFOS alsoinducedcytochromeP450 activity.Male mice administeredperfluorooctanseulfonicacidata concentratioonf0.05% weight/weightin thedietfor5 daysresultedinweightlossand increasedperoxisomalfattyacidbetaoxidationp,eroxisomalcatalaseactivity&,2-hydroxylatioonflauricacid,cytosolic epoxidehydrolaseactivitaynd cytosoliDcT-diaphoraseactivit[ySohleniuseta].,1993]. Haughom and Spydevold[1992]fed 0.02% perfluorooctanseulfoniaccidinthe dietfor7 - 14 days to male Wistarratswhich resultedin increasedliverweight,liver triacylglycerolli,verfreecholesteroalnd decreasedlivercholesteroelsteras wellas decreasedserum cholesteroalnd triacylglycerloelvelsT.here was reducedcholesterol synthesisfrom acetatep,yruvateand hydroxymethylglutaratbeutno reductionin synthesisfrom mevalonicacid inthehepatocytesfrom thetreatedrats.The activitoyf liverhydroxymethylglutariaccid-Co-Areductase(IB4G-CoA) and acyl-CoAcholesterol acyltransfera(sAeCAT) was reduced.Haughom and Spydevold [1992]suggestedthatthe hypolipidemiceffectofperfluorooctanseulfonicacidmay be due todownregulationof HMG-COA reductaseand ACAT withenhancedfattyacidoxidationintheliver.This would subsequentlyreduceverylow densitylipoprotei(nVLDL) productionby theliver. Page 8 Recently,Nabbefeldetal.[1998]testedthehypothesisthatPFOS and other fluorocompoundsmay actasperoxisomeproliferatobrysdisplacinfgattyacidsfrom liver fattyacidbindingprotein(L-FABP). 10 pM PFOS causeda 66 percentreductionofthe fluorescentlyabeledfattyacidanalogll-(5-dimethylaminonapthalenesulfphonyl)undecanoicacidfrom L-FABP invitro.Comparable resultwsere observedforbovine serum albumin.These findingsdemonstratedthatPFOS has a highaffinitfyorfattyacid carrieprroteinsand can displacetheendogenous ligand. Resultsfrom threesubchronicstudieshave been reported[Goldenthaletal., 1978a;1978b; 1979].PFOS was fedinthedietofCharlesRiverCD ratsat0 (control), 30, 100,300, 1,000and 3,000ppm for90 days [Goldenthaletal.,1978a]. At the300, 1,000and 3,000ppm dosage levela,llratsdiedpriorto scheduledtermination.Toxicity signsincludedemaciation,convulsionso,cularand anogenitaldischargesi,ncreased sensitivitoyexternalstimuliand reducedmotor activityB.stopathologyshowed compound-relatedlesionswhich includedhepatichypertrophyand necrosist,hymic and splenicfolliculartrophy,bone marrow hypocellulariatnyd atrophyof mesentericlymph nodes,smallintestinavlillaind skeletamluscle. Among the 100 ppm dose group there was weight loss,elevatedplasma creatininpehosphokinase,alkalinpehosphatase,blood glucoseand blood ureanitrogend,ecreasedhemoglobin,hematocrite,rythrocytaend leukocytecounts,hepaticenlargementand necrosisa,nd stomach discoloratioannd hemorrhage. Among the30 ppm dosegroup therewas weightloss,elevatedplasma glutamate-pyruvatetransaminaseand plasma glutamateoxalacetatteransaminase,and liverdiscoloration. Page 9 Inasubchron(i9c0day)study[Goidentheatall.1,979]t,womaleandtwofemale rhesumsonkeyspergroupreceive0d(contro1l0),,30,100and300mg/kg/daoyfPFOS by oralgavage. All animals(exceptcontrolsd)iedwithin20 days and timingwas related todosage. Monkeys treatedwith300 mgtkg/daydiedbetween thesecond and fourthday. Monkeys treatedwith 100 mgtkg/day diedbetweenthe3d and 5h day. Monkeys treated at30 mg/kg/day diedbetweenthe7h and IOh day and thosetreatedat 10 mg/kg/day died between the IIth and 20'hday of thestudy.Signsof toxicitayteach dosage levelwere comparable and includedanorexia,diarrhead,ecreasedactivitye,mesis,weight loss, marked weakness,prostrationa,nd generalbody tremors.There were no consistent histopathologicchanges withexposure.Adrenalchanges,includingcongestion, hemorrhage and lipiddepletionof theadrenalcortex,were observedin afldose groups. An additionaslubchronicrhesusmonkey studywas subsequentlyinitiateadtmuch lowerdosages[Goldenthal1,978b]. PFOS was administerebdy oralgavage totwo male and two femalemonkeys atdosagesof 0,0.5,1.5or4.5mg/kg/day for90 days. Animals treatedatthe4.5mg/kg/daydosage leveldiedor were sacrificeidnextremisby the seventhweek withsignsof gastrointestintaolxicitcyomparable tothoseobservedinthe previousrhesusmonkey studyby Goldenthaletal.[1978a].Also,in the4.5 mglkglday dose group,mean serum cholesterollevelsdeclinedfrom 183 mg/100 ml to99 within30 days.SGOT increasedfrom 36 to 95 uA and alkalinpehosphatasedecreasedfrom 1088 to 590 u/1. SGFIT remainedunchanged. lestopathologsyhowed compound-related marked diffuselipiddepletionof theadrenalsas wellas diffuseatrophyof thepancreatic exocrinecellsA.nimals inthe0.5mgfkg/day and 1.5mg/kg/daydosage groups survived to theend ofthestudy. Occasionaldiarrheaa,norexiaand emesiswere observed.There Page 10 was a decreasein serum alkalinephosphataseand inorganicphosphateinthe 1.5 mgtkg/day group and a slightdecreaseinalkalinephosphataseinthe0.5mg/kgtday group attheend of 90 days.festopathologywas unremarkableinbothdosage groups. A no observableadverseeffectlevel(NOAEL) was notidentifiefdrom any ofthe above threesubchronic(90day)studies.The resultfsrom thesethreesubchronicstudies suggesttheremay be a potentiaflorcumulativetoxicitoyvertimewiththeprimarytoxic effectrelatedto metabolicwasting.This may be due toan effecotn peroxisome proliferatiofna,ttyacidmetabolism,membrane functionp,roteinsynthesiasnd/or mitochondrialbioenergetics. To date,thereareno dataregardingthechronictoxicitaynd carcinogenicitoyf PFOS. PFOS was not observedtobe mutagenicinseveralSalmonellatyphimurium strainwsith or withoutmetabolicactivatio[nJagannathand Brusic,1978]. PFOS was negativeinan invivomouse bone marrow micronucleusassay[Murli,1996]. There have been two teratologsytudiesconductedwithPFOS. Oral administrationv,iacom oil,of PFOS atdoses of 0, 1,5 and 10 mg/kg/dayto pregnantrats duringdays 6 - 15 of gestatiornesulteidn fetuseswithwhat was initialrleyportedas teratogenicchangesintheeye. [Gortneretal.,1980].These fetalensabnormalities were subsequentlyinterpretetdobe artifactosf thetissuesectioninpgrocess.Maternal body weightsin thehighdose groupwere significantrleyducedbutno significant treatment-relatteedratogeniocr embryotoxiceffectswere reported.Inthesecond teratologystudy,PFOS was administeredincom oilby oralgavage togroupsof 25 pregnantratson days 6 - 15 ofgestatioantdoses of 0, 1,5 and 10 mg/kg/day [Wetzelet al.,1983].Matemal body weightsand food consumptionat5 and 10 mg/kg/day were Page II significantrleyducedcompared tothecontrolanimals. Two femaleratsinthe highdose group diedbeforeday 20. Clinicalsignsin survivingdams includedhunching,thinness, alopeciar,ough haircoatand anorexia.Treatment-relateedffectsp,rimarilyoccurringin thehighdose group,includedincreaseresorptionasnd fetaldeath,decreasedfetalbody weight,delayedskeletaolssificatiocnl,eftpalate,subcutaneousedema and cryptorchidism. During thepast 15 to20 yearstherehave been severalendeavorsdesignedto ascertaitnhehealthand exposurestatusof workers involvedwithfluorochemical productionatthecompany's Decatur,Alabama and Antwerp,Belgium plants.Medical surveillancheas been routinelcyonductedof fluorochemicalproductionworkersatboth plants.Medicalsurveillancaectivitiaensalyzedfortotalserum organicfluorinleevels untilthemid-1990'swhen serum PFOS determinationq,uantifiablbey liquid chromatographymass spectrometry,became incorporatedinthebiennialmedical surveillanceexaminations.However, we areaware of one occasionin 1979 where the serum of 5 Decaturemployees was measured forPFOS by electroncapturegas chromatographand microwave plasmadetectionmethods [CentralAnalyticaLlaboratory, 1979].Totalserum organicfluorinleevelsforthesefiveemployeeswere 10.1,5.7,9.4, 11.8and4.lppm. The percentofPFOS foundwas 60%,70%,80%,55% and 65% of thetotalserum organicfluorinleevels,respectivelyI.n 1981,selectecdlinical chemistriesand hematology valuesofDecaturemployees inthechemicalplantwere compared tothoseresultosf employeesintheadjacent3M filmplant[Roach,1982; Schuman, 1982].There were no significacnotrrelatiocnoefficienbtestween totalserum organicfluorineand gamma glutamyltransferases,erum glutamicoxaloacetic Page 12 transaminases,erum glutamicpyruvictransaminasea,lkalinephosphatase,cholesterol, hemoglobinorredblood counts. However, thisanalysiwsas limitedinscope(no dose responseanalysis)d,id not analyzespecificalfloyrPFOS, and didnot accountforseveral potentiaclonfoundingfactors.Another researchinitiatiivnetothehealthstatusof Decaturemployees was a retrospecticvoehortmortalitystudy(1961 - 1991)conductedof former and currentemployees who had worked atleastone yearattheDecaturplant [Mandel and Johnson, 1995].Vitalstatuwsas determinedfor99.7% ofthe 1,957cohort members who had,worked inthechemicaland filmplants.A totalof 74 deathswere identifiecdompared to 117.7expected(U.S.rates).Among male employees who had worked onlyin theDecatur chemicalplant,therewere 32 deathscompared to 44.1 expected. There were no specificausesof deaththathad significantellyevated standardizemdortalityratios.Because ofitsmore recentconstructioinn the1970's, therehas notbeen a retrospectivceohortmortalitystudyconductedof employees atthe Antwerp plant. The purposeof thisreportistoprovidean aggregateanalysisof the hematologicalc,linicaclhemistryand hormonal parameters,as measured in themedical surveillanceexaminationsof Antwerp and Decaturemployees intwo separatetime periods,inrelatiotnotheworkers'serum PFOS levelsA.lthough femaleemployees also participateidn thesemedicalsurveillanceexaminations,theiractualnumbers were too few to providemeaningfulstatisticaanlalysis. METHODS PFOS Production Page 13 PFOS productionbegan inAntwerp in 1976 and inDecatur in 1961. In general, perfluorinatecdhemicals areproduced viaan electrochemicalprocess:a solutionof organicsubstrateiselectrolyzedinanhydrous hydrogen fluorideata low voltage(Simons and Bryce, 1954).Basicallyt,he productsof thiselectrolysicsellreactionare highly fluorinatecdompounds with theend-product@efinedby the startinmgaterial.Products manufactured atthesetwo plantsinclude:ScotchgardTm brand fiber,leatherand carpet protectorU-g,ht WaterTm brand aqueous filmfonming foam (AFFF); ScotchbanTM paper treatment;Kel-F7m brand plasticand FluorelTmbrand elastomers. SubjectSelection General medical surveillancoeccursbienniallyforemployees atboth of these plants.Participatioinsvoluntarywith approximately100 Antwerp and 250 Decatur employees eligibleforsurveillanceA. totalof 88 Antwerp employees participateidnthe medical surveillancexaminationsin theSpring,1995 and 90 Decatur employees participateidntheFall,1994. IntheFallof 1997,a totalof 149 employees (Antwerp 65;Decatur = 84) participateidnmedical surveillanceexaminations.For purposesof brevity,thesetime periodswillbe referredto as 1995 and 1997. Altogether,61 employees participateidnboth examinationyears(1995 and 1997). This lower number was due to a largeturnoverof employees atboth plantlocationsduring 1996-1997. For each time period the surveillancceonsistedof a medicalquestionnairem,easurement of height,weight and blood pressure,standardclinicalchemistryand hematology tests,and determinationof serum PFOS levels. Page 14 In 1995,severalhormones were alsoanalyzedfor male employees who were judged a priorito have had likelyPFOS exposure(i.e.t,hoseworking inor inthe immediatevicinitoyfthePFOS productionarea).Of the88 Antwerp employees,50 had hormone measurements. Of the90 Decaturemployees,38 underwenthormone measurements. PFOS Analysis In 1995 theanalysisforserum PFOS was conductedby 3M'S Environmental Technology Servicesin St.Paul,Minnesota.The method usedtetrabutylammoniumto ion-paiwrithPFOS inserum. The ion-pairwsere thenextractewdithethylacetate.The abstractiopnroductwas thenanalyzedusinghighperformanceliquidchromatographythermospraymass spectrometry[Johnsonetal.,1996]. In 1997 theserum sampleswere analyzedby TurbolonSpray liquidchromatography/massspectrometryusingselectedion monitoringinthenegativeionmode by Advanced BioanalyticaSlervicesI,nc.[Anderson etal.,1997a;1997b].The lowerlimitofquantitatiownas 0.1gg/mL forPFOS. LaboratoryAnalyses For bothtime periods,theUnitedLaboratoryServices(St.Paul,Minnesota) performedthestandardhematologicaland clinicaclhemistrytests.These includedthe followinghematologicatlestsh:ematocrit(percent)h,emoglobin(gm/dl)r,edbloodcells (RBC, looo/MM3), whitebloodcells(WBC, Iooo/ MM3 )and platelectount(1000/ MM3); and thefollowingclinicaclhemistrytestsa:lkalinpehosphatase(IIJ/L)g,amma glutamyltransferas(eGGT, IU/]L)a,spartataeminotransferas(eAST, IUAL)formerly Page 15 known as serum glutamicoxaloacetiaccid(SGOT), alanineaminotransferas(eALT, IU/L)formerlyknown as serum glutamicoxaloacetitcransaminase(SGPT), totaland direcbtilirubi(nmg/dl)b,loodureanitroge(nBUN, mg/dl),serumcreatinin(emg/dl), glucose(mg/dl)c,holestero(lmg/di)h,ighdensitycholestero(lHDL, mgldl)and triglycerid(emsg/di).Low densitylipoprotei(nmgldl)was calculateadsthefollowing: LDL = [cholester-oHlDL -(tiyglycerides/5)]. Eleven hormones were assayedin 1995:cortisold,ihydroepiandrosteronseulfate (DHEAS), cstradiolf,olliclsetimulatinhgormone (FSH),17 alphahydroxyprogesterone (17-BP),freetestosteronteo,taltestosteronleu,teinizinhgormone (LH),prolactin, thyroidstimulatinhgormone (TSH) and sexhormone bindingglobuli(nSHBG). Allbut SBBG (EndocrineScienceReferenceLaboratoryT,ar-zanaC,A) were analyzedatthe Universityof Nfinnesota'EsndocrinologyLaboratory. Cortisolwas assayedusinga fluorescencpeolarizatioinmmunoassay (Abbott TDx). Radioimmunoassays(RIA)were usedforDHEAS (Pantex)e,stradio(lmodified Pantex),17-HP (modifiedCIS)and totaltestosteron(eDiagnostiPcroductCorp.Coat-A Count). Free testosteronweas determinedusingequilibriudmialysisL.H, FSH and prolactiwnere assayedusinga microparticleenzyme immunoassay (AbbottImx). TSH was determinedusinga chemiluminescenceimmunometric assay(Nichols).SBBG was assessedviaa radioimmunoassayafterchromatographicsample purificatio(nEndocrine ScienceReferenceLaboratory).Bound testosteronweas calculateads totaltestosterone lessfreetestosterone. Data Analysis Page 16 Descriptivesimpleand stratifiaendalyses,Pearsoncorrelatiocnoefficients, ANOVA and ordinarymultivariablreegressionwere usedto evaluateassociations between PFOS and each hematologicaland clinicaclhemistrytestand hormonal assay. Age, body mass index,currentalcoholconsumption(chinksper day)and cigarettuese (cigarettessmoked per day)were potentiaclonfoundingfactorsthatwere consideredin theanalyses.For stratifiaendalysese,mployees were dividedintofourPFOS categories: 0-1 ppm, I -< 3 ppm, 3 -< 6 ppm and > 6 ppm inordertodetermineifan effectexisted atthehighestserum PFOS levels.Other categoricaclutoffpointswere alsoused which providedsimilarresults.For multivariablreegressioannalyses,PFOS and thepotential confoundersof age,body mass index(BNU), alcoholuseand cigarettuese were examined as continuousexplanatoryvariableisnthemodels. Multivariablreegressionmodels were fittewdith PFOS analyzedas a continuousvariableusinglinearaswellas non-linear transformation(squadratics,quare,squarerootand inverse)inordertomaximize the possibilitoyf findingassociationbsetween PFOS and thedependentvariableof interest. Linearand nonlinearrelationshipwsere examined by residualdiagnosticussing studentizedand Cook's distancevalues.Naturallogtransformationosf thedependent variablewsere performed,when necessary,tonormalizevariableasnd toenhance model fit.Traditionasltepwiseselectiopnrocedureswere alsoemployed (selectioinnand out of model was setatp = 0.1)as wellas takingintoaccountothercovariantsthatmay be on thebiologicpathway of effect[Greenland,1989].We didnotexamine changesin measured PFOS between thetwo timeperiodsbecausetheestimatedhalf-lifoef PFOS is atleasttwo years. Studyresultwsere analyzedusingtheSAS System [1990]. Page 17 Analysesarepresentedby plant,yearand thethreemajor groupsof participants: allemployeeswho participatiendeach year(1995:N = 178;1997:N = 149);only those employees(N = 61) who participatiendbothyears;and onlythoseemployees (N = 88) who participateidn thehormone measurements in 1995. RESULTS The distributioonf employees,by serum PFOS exposurecategorizatioins, presentedinTable 1. Whereas 20 percentof theDecaturemployees had exposuresat> 3 ppm forboth years,thisproportioninAntwerp went from 25 percentin 1995 to 13 percentin 1997. For both years95 percentof themeasured serum PFOS levelswere below 6 ppm. There were no PFOS measurements > 6 ppm inAntwerp in 1997. The overallmean valuesof PFOS, demographic,serum chemistryand hematologicalparametersforbothlocationsa,s wellas each locationseparatelya,re presentedin Tables2 and 3,respectivelyI.n particulatrh,eAntwerp male employee populationwas significantyloyungerthanDecatur,had lower body mass indicesand higherself-reportdeadilyconsumptionof alcohol. In additiont,heirclinicaplrofiles were alsodifferenftorseveraltests.The Antwerp employees had lowermean alkaline phosphatase,creatinineg,lucoseand triglycerivdaeluesand highertotalbilirubinH,DL and hematocritvalues. PresentedinTable 4 arethePearsoncorrelatiocnoefficientbsetween PFOS and theselectedparametersof interesbty bothlocationcsombined, each locationseparately, and by yearofexamination.In 1995,variabletshatwere significant(lpy<.05) correlatewdith PFOS forbothlocationcsombined includedtotalbilirubinw,hiteblood Page 18 cellsand plateletsA.lthough creatininweas not significantcloyrrelatewdhen both locationwsere examined,itwas negativelcyorrelatewdith PFOS inAntwerp but positivelcyorrelateidnDecatur. In 1997,variabletshatwere significantcloyrrelated withPFOS forboth locationcsombined were BNU, ALT, direcbtilirubinc,holesterol, LDL and hematocrit.InadditionG,GT and triglyceridweesre significantploysitively correlatewdithPFOS among onlyAntwerp employees. Providedin Table 5 arethemean, median,standarddeviationand range of the covariateasnd theclinicaclhemistrieasnd hematologicalparametersby fourlevelsof PFOS categorizatio(n0 -< 1,1 -< 3,3 < 6 and > 6 ppm) forbothyears.Several observationasrenoteworthy. First,themean forthe > 6 ppm PFOS categorywas one orderof magnitude higherthanthelowestPFOS category(0 -< Ippm) forboth years. Also,themeans of thefourPFOS categoriewsere significantdliyfferenftrom each other. Second, theyoungestemployeeshad thelowestserum levelsof PFOS. Third,therewas onlyone variablet,otalbilirubiwnh,ich had significan(tp< .05)F testsfordifferenceisn means inboth yearsof analysis. Besidestotalbilirubint,heonlyothervariablein which themean of thehigherlevelsofPFOS exposure(3 -< 6 ppm or> 6 ppm) was significantdliyfferenftrom thelowestcategorylevelofPFOS exposure(0-< I ppm) was forWBC's in1995. This was notobservedin 1997. The lowestmean platelectountwas observedatthehighestPFOS exposurecategoryinboth years althoughthemean platelet countsby PFOS categorieswere not significantdliyfferenftrom eachother. Providedinthenexttwo tablesarethemean, median,standarddeviationand rangeof thecovariatesand theclinicaclhemistriesand hematologicalparametersby the fourlevelsofPFOS categorizatifoonreach plantfor1995 (Table6)and 1997 (Table7). Page 19 In 1995 (Table6)inAntwerp only,alcoholconsumptionwas associatewdith higher PFOS levels.Mean serum creatininleevelsdeclinedin Antwerp but increasedin Decatur employees. Antwerp employees inthe3 - < 6 ppm PFOS categorysmoked more cigaretteasnd had higherWBC levels.In 1997,Antwerp employeesinthe lowestPFOS exposurecategorywere significantyloyungerthantheircounterparts.Antwerp employees inthehigherPFOS categorylevelshad highermean alcoholconsumption levels.Mean cholesterolL,DL and triglycerildevelstrendedupwards by PFOS exposurecategoriesforAntwerp employees. Linearand nonlinearrelationshibpestween PFOS and thedependentvariableosf interest,akingintoaccountthepotentiaclonfoundingaffectosf age,BNE, alcoholand cigaretterse,sultedinnumerous analyses.For purposesof brevityl,inearregression models arepr-esenteidnTable 8 which show theeffectthattheparameterof interest, PFOS, has on thevariousdependentvariablesa,djustedforage,body mass index,alcohol and cigarettuese. These covariatewsere analyzedas continuousvariablesI.n thecaseof serum creatininaend totalbilirubian,quadratic(PFOS + PFOS2) analysisprovidedthe beststatisticmaoldel of thedataadjustedforthefourpotentiaclonfounders.The natural logtransformatioonf totalbilirubiGnG,T and glucoseprovidedthebestfitforthese responsevariables.PFOS was significantalsysociatedp( <.10) inbothyearsforonly one clinicaplarameter:totalbilirubinP.FOS was associateidnone of thetwo yearsfor thefollowingvariablesd:irectbilirubicnr,eatininec,holesteroLlD,L, HDL, hematocrit, hemoglobin and platelectount. Those variablesthatwere observed tobe associatedinatleastone yearin the regressiomnodels inTable 8 are separatedby plantlocationand yearinTable9. After Page 20 separateanalysesby employee population,onlytwo variablest,otalbilirubiannd HDL, remainedsignificant(lnyegativelya)ssociatewdithPFOS foratleastone plantlocation forbothtimepeiiods.Totalbilirubisnhowed a significantegativeassociatiownith PFOS (quadratircelationf)oremployeesattheDecaturplantinboth years.There were no significanatssociationasmong theAntwerp populationbetween PFOS and total bilirubin.HDL was significantnleygativelayssociatewdith PFOS inAntwerp inboth 1995 and 1997 but was not significantalsysociatedwithPFOS inDecaturineitheryear. As forinconsistenatssociationosbservedinTable 8,directbilirubiwnas not significantly associatewdithPFOS ineitherplantlocatio(nTable9).The quadratiacssociatiofnor PFOS withcreatininweas observedinAntwerp in 1995 and Decaturin 1997 butnotin Antwerp in1997 orDecaturin1995. Cholestero(landLDL) was observedtobe positivelayssociatedwithPFOS onlyinDecaturin 1997.Hematocritand hemoglobin were associatewdith PFOS onlyinDecaturin 1997. Platelectountswere observedto be significantnleygativelyassociatewdithPFOS onlyinDecaturin 1995. Traditionasltepwiseregressionmodelingtechniqueswere alsoused as wellas testingmodels with variabletshatwould be consideredon thebiologicaplathway of effectforany dependentvariableT.he association(sorlackthereoff)rom theseanalyses were similartowhat has been presentedinTables8 and 9. For purposesof brevitythese analysesarenot shown. To furtherunderstandtheassociatiobnetween totalbilirubiannd PFOS, scatter plotsarepresentedforboth timeperiodsand by locationinAppendix A. Inaddition, unconjugatedbilirubiwnas alsocalculate(dtotablilirubi-ndirecta)nd thesescatteprlots arepresentedinAppendix B. Table 10 isa summary of thesescatteprlotsfrom both Page 21 Appendices. The strongestassociationasppearedtobe quadraticinnatureprimarilyfor theDecaturlocationand thepercentof variabilietxyplainedrangedbetween 3 (1995 data)and 7 perrent(1997 data).The linearcomponent ofthequadratiwcas negativein directionT.he upward trendappearedtooccuraround 6 ppm PFOS where thedataare sparse.These simplelinearand quadraticmodels were notinfluencedby any one employee accordingto residualdiagnostics. To furtherunderstandthepossibleassociatiobnetween HDL and PFOS, scatter plotsarepresentedforbothtimes and by locationinAppendix C. Both locations combined resulteidn significanetgativelinearand nonlinear(quadratica)ssociationisn 1995 althoughthepercentof variabilietxyplainedin thesemodels rangedbetween 3 and 5 percent.No significanatssociationwsere observedforeach plantlocationin 1995. There were no significanntegativeassociationbsetween HDL and PFOS in 1997 for eitherthecombined locationsor each separateplantsite. Providedin Tables II through14 aretheanalysesrestrictetdothe61 employees who participateidn surveillancienbothyears.Table IIprovidesthemean valuesfor each parameterfortheemployees who participateidn bothexams compared tothosewho participatiendonlyone ofthetwo years.Overallt,herewere few differences.The mean age of the61 employees was lowerthanthatof the 1995 employees who didn't participatien 1997. Conversely,themean age of the61 employees was higherthanthat ofthe 1997 employeeswho didn'tparticipaitne 1995. Cholesteroalnd I.DL were significanthliygherinthe61 participantisn 1997. Tables12 and 13 presentthemean valuesby plantlocationfor1995 and 1997,respectivelOyf. these61 employees,27 were from Antwerp and 34 from Decatur. Of noteworthyimportancearethedifferences Page 22 between the27 Antwerp employeesand theirfellowemployeesin1997 (Table13). The 27 Antwerp employees had significanthliyghermean PFOS exposures,were significantollyder,had greaterBNH's and highercholesterovlalues. Multivariable regressionanalysesforthe61 employees arepresentedinTable 14. The onlysignificant associatiownith PFOS appearedto be with s@rum creatinin(equadratici)n 1995. Regardlessofplantlocationm,ean PFOS levelswere higherforthoseemployees who were selectedforhormone measurementsin 1995 (Table15).Thiswas expectedas theseemployees were selectedwiththea prioribeliefthattheirserum measurements would be higherdue totheirworkplaceexperience. For example,ofthe42 employees in 1995 whose serum PFOS levelswere > 3 ppm, 76% had hor-rnonemeasurements. PresentedinTable 16 arethemean valuesforPFOS, demographic,serum chemistriesand hematology forthoseemployees who had hormone measurements compared tothoseemployees who didnotin 1995. Those employees who had hormone measurementswere younger,higherusersofalcohol(Antwerponly)and cigarette(sboth locations)a,nd had lowerserum creatinin(eAntwerponly)and higherVIBC levels(both locations).The latteorbservatioinsconfounded by cigarettsemoking as among nonsmokers,thoseselectedforhormone measurements had a mean WBC of 6.24 compared to6.03fornon-selecteedmployees (p=.36). Among smokers,thoseselectedhad a mean WBC of 8.69compared to8.06fornon-selecteedmployees(p= .23). Allotherclinical parameterswere comparable,by PFOS exposurecategories,between subjectswho had hormone measurements and thosewho did notin 1995 (Tables17 and 18). The Pearsoncorrelatiocnoefficientbsetween PFOS and thehormones tested among the88 employees werethefollowingc:ortiso(l.07)D,BEAS (-.13)e,stradiol Page 23 (.09)F,SH (.06)1,7-hydroxyprogester(o-n.e04)L,H (.03)p,rolacti(n.06)S,HBG (.11), freetestosteron(e-.06)b,ound testosteron(e.06)T,SH (.01).None were statistically significant. PresentedinTable 19 arethemean, median,standarddeviationand range of the varioushormones by thefourPFOS categories0:- <1 ppm, I -< 3 ppm, 3 -< 6 ppm and 2!6 ppm. Severalobservationasrenoteworthy.Firstt,hemean age of thelowestPFOS exposurecategorywas 10 yearslessthanthatof thehighestexposurecategory.Therefore itwas not unexpectedto observethatthemean DBEAS, 17-HP, freetestosteronaend bound testosteronleevelsofthislowestexposurecategorywere greaterthanthemeans of thehigherPFOS exposurecategorizationAsd.justingforthedifferenceisn age (aswell astheotherthreepotentiaclonfounders)intheregressiomnodels (Table20) resulteidn no significanatssociationbsetween PFOS and thehormones analyzed,exceptfor estradiol.With estradioal,quadratimcodel providedthebestfitofthedataand both PFOS termswere significantU.pon residuadliagnosticistwas determinedthatthis estradiomlodel was influencebdy one specifiecmployee (employeeA).The influenceof employee A isbestseen inFiguresI and 2 which aresimplescatteprlotsof boththe linearand quadraticfitsof estradioalnd PFOS, withand withoutemployee A, respectivelyE.mployee A had a 12.83ppm serum levelof PFOS which was thehighest valuerecordedin 1995. Es estradiovlaluewas 92 pg/dl(seeupperrighthand comer of Figure1).Employee's A estradiovlaluewas alsoinfluencedby thefactthathisbody mass indexwas 33 kgtM2. Exclusionof thisemployee resultedina nonsignificant quadraticequationT.he variabili(tRy2)of thedataexplainedwent from 7.6 percentto2.1 percentupon exclusionof thisemployee. The slopeofthelinearequationchanged from Page 24 positivteonegativealthoughitwas nonsignificanitnbothFiguresI and 2.Finallyi,t shouldbe notedthattheestradiomlodels in Table20,withand withoutemployee A, did predicttheknown positiveassocatiobnetween estradioalnd body mass index. DISCUSSION We conductedtwo cross-sectionaanlalysesofsurveillancdeatatoexamine the associationbsetween serum PFOS levelsand severalhematologicalc,linicaclhemistry and hormonal parametersin male fluorochemicalproductionemployees. For bothyears, 95 percentof themeasured serum PFOS levelswere below 6 ppm. Because theAntwerp and Decaturemployees were dissimilabry age,body mass indicesand self-reported alcoholuse,we conductedcombined as well as separateanalysesby plantlocation. These threedemographic differencelsikeleyxplainwhy theAntwerp employees had lowermean serum levelsof alkalinpehosphatase,HDL, triglyceridaensd blood glucose [Davem and Scharschmidt,1993;Lewis,1994;Friedman,1998;Fu, 1998;Wolf, 1998]. In thepresentstudy,alkalinpehosphatase,GGT, AST and ALT valueswere not significantalsysociatedwiththemeasured serum PFOS levels.This was an a priori questiondue to thefactthatPFOS: 1)isa peroxisome proliferatoirntherat[Ikedaetal., 1987;Sohleniusetal.,1993];2) resultedinslightomarked increaseisnplasma glutamicoxalaceticand pryuvictransaminaselevelsina 90 day studyof ratsfeddiets which containedPFOS at100 ppm alongwith hypertrophyand livernecrosisobservedat histopathology[Goldenthal,1978a];and 3) increasedSGOT and decreasedalkaline phosphataselevelsin monkeys afteradministrationb,y oralgavage,for30 days of doses of4.5mg/kg/dayofPFOS (Goldenthal1,978b]. On theotherhand,SGPT values Page 25 remainedconstantand no histopatholociacbnormalitiewsere notedintheliversof these monkeys which died by the7"'week ofthestudy.No significalnitverenzymaticor histopathologcyhanges occurredinmonkeys inthe0.5and 1.5mgtkg/daydose groups. We did observea quadratiacssociatiownith totalbilirubianmong onlythe Decaturemployees. We do notsuspectthisi@a biologicaalssociatiobnecausethe bilirubilnevelswere withinthenormalreferencerange. Also,thepercentvariability explainedof totalbilirubibny PFOS intheregressiomnodels was low.The Antwerp employees'totalbilirubilnevelswere significanthliygherthantheDecatur employees'levels.We offerseveraplossibleexplanationfsorthisobservation.Firstw,e suspectthere may be a greaterprevalenceofGilbert'syndrome [Lidofskyand Scharschmi.dt1,993;Friedman,1998]among theAntwerp employees.In 1995,15 (17%) Antwerp employees had totalbilirubivnalues> 1.2mg/dlcompared to3 (3%) Decatur employees'levels.In 1997,therewere 9 (15%) Antwerp and 2 (2%) Decatur employeeswith totalbilirubivnalues> 1.2mg/dI. However, therewas not a concomitantdeclineinbilirubicnonjugatio(ni.e.d,irectbilirubilnevelsa)s might be expectedamong individualdsiagnosedwithGilbert'syndrome. Neverthelesse,xclusion of thesepossibleGilbert'syndrome employees stilrlesultedinhighermean total bilirubivnaluesamong theAntwerp employees in bothyears.Secondly,therewere four Antwerp employees who self-reportheedpatitiAs historieasnd one employee selfreporteda historyof HepatitiBs. Fishand shellfischonsumptionislikelymuch greaterin Antwerp thanDecaturdue toitsvicinitnyeartheNorth AtlanticT.hird,bilirubiinsa tetrapyrroltehatisan end-productof heme degradation[Lidofskyand Scharschmidt, 1993]. Bilirubilnevelsmay be increasedue todisorderosfbilirubimnetabolism,liver Page 26 diseaseand obstructioonfthebileducts. Other hematologicaland clinicaclhemistry resultdsid notsuggesttheseconditionsexistedamong theDecaturemployees. Fourth, post-collectipornoceduresmay resulitnerror.Totalbilirubidneterminatiomnay be falseldyepressedifhemolysisispresentbecauseof increasedabsorbencein theblank [Kaplanand Pesce,1984]. Bilirubiinsalsos@nsitivteo and destroyedby lightand heat. We areuncertainwhetherthesefactorscouldhave contributetdothelowertotalbilirubin levelsintheDecatursamplesinbothyears. Finally,thelinearcomponent ofthe quadraticassociatioonbservedamong Decaturemployees isnegativeindirectioinn relatiowniththeirmeasured PFOS levels.That is,totalbilirubilnevelsdeclinedwith increasinPgFOS levelsW.e would expecta positiveassociatioinfPFOS impaired bilirubicnonjugationT.he trendupwards inthequadraticappearstooccuratlevels6 ppm and higherwhere thedataaresparse.We concludethattheassociatioonbservedamong onlytheDecaturemployees isunlikelytobe relatedto serum levelsof PFOS. We didobservea positiveassociatiobnetween serum PFOS and serum cholesterol levelsin the1997 time periodforDecaturemployees. Thisresulitsunlikelyto have a biologicaelxplanationas PFOS isa known peroxisome proliferationrtheratand was shown to have hypolipidemicpropertieisnrhesusmonkeys [Ikedaeta].,1987; Sohlenius etal.,1993;Goldenthal1978b;1979]. Rhesus monkeys fedPFOS at4.5mg/kg intheir chow had serum cholesterovlaluesreducedfrom 183 mg[L to99 mg/L within30 days. Rhesus monkeys fed 1.5mg/kg inthechow had cholesterollevelsreducedfrom 195 mg/kg toIII mglkg within90 days [Goldenthal1978b].As forHDL, althoughthe mult.ivariabalnealyseswere suggestiveof a negativeassociatiobnetween HDL and PFOS Page 27 inAntwerp (butnotDecatur),thescatteprlotspresentedinAppendix C do not support thenotionof a biologicaalssociatiobnetween PFOS and HDL. Itshouldbe notedthattotalorganicfluorinelevelsp,rimarilyconsistingof perfluorooctanoiacid(PFOA, C7Fl5COO-),a sevencarbonperfluorinatecdarboxylic acid,were reportedto reducetheeffecthatalcoholhas on HDL levelsamong higher exposedmale PFOA productionworkersinCottageGrove,Minnesota [Gillilanadnd Mandel, 1995]. However, thisfindingwas notobservedinsubsequentanalysesof these employees(Olsenetal.,unpublishedfindings).Thisobservatiobny Gillilanadnd Mandel was testableinthepresentstudyas both Antwerp and Decaturemployees had measurablequantitieosf PFOA. We didnotobservea significanntegativemodulationof theeffectof alcoholconsumptionon HDL levelsamong Antwerp and Decaturemployees with higherserum PFOA levelsalthoughtheirserum levelswere approximately3 to5foldless,on average,thanthatreportedinCottageGrove employees [Olsenetal.,1998]. The Antwerp and Decatur employeeswere exposed toPFOA, notinitsactualproduction, butratherinitsuse as a surfactanitntheproductionoffluoropolymers.In 1995 the mean serum PFOA levelamong theAntwerp and Decaturemployeescombined was 1.46 ppm (range0 - 13.20ppm) and in 1997 themean serum levelwas 1.57ppm (range0.11 11.10).Stratifiebdy plantlocationt,he 1995 and 1997 mean serum PFOA levelswere 1.19 and 1.78ppm intheAntwerp employees and 1.72and 1.40ppm intheDecatur employees,respectively. The multivariablreegressiomnodels showed a negativeassociatiobnetween PFOS and platelectountsatPFOS levelsabove 6 ppm in 1995 and thistrendwas also apparent,althoughto a lesserextent,in 1997. Neverthelessp,lateleltevelswere well Page 28 withinthenormal referencerangeinbothtimeperiods.This associatioinsnot supported by a 90 day subchronictoxicitsytudywhich showed no declineinplatelectountsfor monkeys fed0.5,1.5or4.5 mg/kg forup to90 days [Goldenthal1,978b]. Mean platelet countsamong the 1.5mg/kg/day and 0.5mg/kglday dosegroups were 226 and 231 (103/CMM) compared to218 in thecontrolgroup [Goldenthal1,978b]. There were no platelectountsreportedinthe90 day ratstudyalthoughattheend of 3 months of study therewere slightomoderate decreasesinhemoglobin,hematocritand erythrocytceounts observedformale and female ratsinthe 100 ppm dose group [Goldenthal,1978a]. No consistenatssociationwsere observedbetween PFOS and hemoglobin,hematocritor RBC valuesinthepresentepidemiologicinvestigationI.n a priorsubchronicrhesus monkey studythatwas abortedearlydue toallanimalsdiedby the20'hday,mean platelet countswere 203,219, 136,172 and 185 forthe300 mg/kgtday,100 mglkg/day,30 mgtkg/day,10 mg/kg/day and controlgroups,respectivel[yGoldenthal1,979]. Aftercontrollinfgorage,a confounderformale testosteronheormone levels[Dali etal.,1981;Griffinand Wilson,1994],we observedno significanatssociationwsith serum PFOS measurements. We didobservea quadraticassociatiobnetween estradiol and PFOS. Upon furtherexamination,thisfindingwas influencedby one particular employee who had thehighestPFOS levelbutwas confounded by theindividual'lsarge body mass index.Exclusionof thisemployee resultedinnonsignificanftindingsT.hus, any interpretatiwointhestradioilsdifficulbtecauseof theinfluencethisone employee has on thestatisticaanlalyses. Itshouldbe notedthatperfluorooctanoaiccid(PFOA), atapproximately50 - 100 ppm levelsinserum,enhances thearomataseconversionof testosteronteoestradioiln the Page 29 rat[Cook etal.,1992;Biegeletal.,1995). However,PFOA productionworkersin CottageGrove with serum levelsup to30 ppm appearednotto have alteredserum estradiollevels[Olsenetal.,1998]. Again,likeHDL, thiswas a testablheypothesis among theAntwerp and Decaturemployees althoughtheirserum PFOA levelswere lowerthanCottageGrove employees. We di@notobserveany significanptositive associatiobnetween estradioalnd serum PFOA levelsin theseAntwerp and Decatur employees. Severalmethodologicalissuesshouldbe consideredinevaluatingtheresultfsrom thisstudy. Firstt,hecross-sectiondaelsigndoes notallowfora directanalysisof the temporalitoyf an associationS.econd,thevoluntaryparticipatiroantesin medical surveillancweere not idealas among eligibleemployees we had 88 and 65 percent participatiionAntwerp for1995 and 1997,respectivelbyu,t only35 to40 percentin Decaturforbothyears. Third,giventhesuspectedlonghalf-lioffePFOS (atleasttwo years),itmay be conceivablethattheremay be some biologicaalccommodation tothe effectosfPFOS which would minimizethepossibiliotfyfindingan association.Fourth, itisknown in laboratoraynimalsthatPFOS concentratepsrimarilyin theliver.Serum measurementsof PFOS may notadequatelyreflecbtody burden. Fiftht,hetwo crosssectionalanalysescannotbe viewed as independentpopulationsas 61 employees were studiedin bothyears. This was due,inpart,to a largeturnoverof employees atboth plantsbetween examinations.Sixth,therecouldbe measurement errorinimportant confoundingvariablesA.nalysisof thedataof the61 subjectswho participateidn both yearsshowed thattherewas excellenctorrelatiofnortheconfoundingfactorsof BNE (r .92,p = .0001),self-reportaesdpectsof alcoholconsumption (r= .88,p = .0001)and Page 30 ci-arettsemoking (r=.79,p=.0001). As expected,these61 employees'serum PFOS levelsforthetwo yearswere highlycorrelate(dr=.92,p = .0001).Seventh,thequality of medicalsurveillancdeata,priortoitsuseforstudyingan a priorihypothesisc,an often be evaluatedby whetherknown positiveassociationasreobserved. In thisregard,we observedvariousexpectedassociationisncludingcigarettsemoking and elevatedwhite bloodcellcountsand largebody mass indicesassociatedwithelevatedlivertransaminase levels[Olsenetal.,1991;Bums etal.,1997].Finallyt,hepulsatilneatureof some of the hormones studied(e.g.F,SH, LH, testosteronhea)s resulteidnpriorrecommendations thatmean hormone measurements shouldbe theresultof pooledblood from multiple samplestakenatshortinterval[sGoldzieheretal.,1976].In our studymultiplesamples were notfeasiblebecauseof thelow probabilitoyf employees voluntarilgyivingthree serum samples overa 45 -60 minute periodof time. In summary, we conductedtwo cross-sectionalnalysesand did notobserve consistentassociationbsy plantlocationor timeforseveralhematologicalparameters, serum chemistriesand reproductivheormones with measured serum PFOS levelsin male fluorochemicalproductionemployees. Ninety-fivpeercentof theemployees had serum PFOS levelsbelow 6 ppm. Our findingssuggestthat,among theseAntwerp and Decatur male fluorochemicalproductionemployees,significanhtematologicalc,linicaclhemistry and hormonal abnormalitiewsere not associatedwithserum PFOS concentrationlsess than6 ppm. Any inferencesderivedfrom thefew employees withserum PFOS levels> 6 ppm would be tenuous,atbest. Limitationsofthisstudyincludeitscross-sectional design,thevoluntaryparticipatiroantes,thefew subjectsexposed atthehighestlevels, Page 31 and thelower levelsof serum PFOS measured among theseemployees compared tothose thatcaused effectsintwo speciesof laboratoryanimals. Page 32 Acknowledgements The authorsgratefullaycknowledgetheassistancoefMicheleBurlew,Martha McGough, Jane Quarfothand thehelpfulcomments of brs.John Butenhoff,Marvin Case and Andrew Seacat. Page 33 References Anderson DJ,Mulvana DE (1997a).Analyticarleportforthedeterminatioonf perfluorooctanoataend perfluorooctanesulfonaitnehuman serum by LC/MS. 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Wolf PL (1991)L.iverfunction.(In)HowanitzJH, HowanitzPJ (eds),Laboratory medicine:testselectioannd interprrtatioNne.w York:ChurchilLlivingstoneInc.,pages 173-190. Page 37 Table I Distributioonf Employees by Year,Locationand PFOS ExposureI-evel(ppm) AllEmRloyees PFOS N (%) N 0 -< Ippm 45 25 I-< 3 ppm 91 51 3 - < 6 ppm 35 20 >= 6 RRm 7 4 178 (100) 1995 Data AntweM (%) N 34 39 32 36 19 22 3 3 88 (100) Decatur (%) N 11 12 59 66 16 18 44 90 (100) AllEmployees (%) N 60 40 63 43 21 14 5 3 149 (100) 1997 D Antwe (%) 31 25 9 0 65 Table 2 Mean, Median, StandardDeviationand Range of Study Parameters,Both Locations,1995 and 1 Variable PFOS Age Alcohol BMI Cigarettes Alk Phos GGT AST ALT T. Bilirubin D. Bilirubin Mean 2.19 40.6 0.7 26.6 6.3 86.2 44.4 27.6 45.9 0.72 0.21 1995 Data Median 1.70 40.0 Std Dev 1.87 8.76 0.1 1.1 25.8 5.1 0.0 10.7 85.0 24.6 36.0 32.1 26.0 10.9 42.0 18.6 0.70 0.37 0.20 0.05 BAnge 0-12.83 21-60 0-6.0 17.9-60.7 0-40 31-191 2-293 13-96 18-183 0.20-2.90 0.10-0.40 1997 Data Mean 1.75 Median Stc 1.30 39.3 0.5 40.0 0.1 27.1 26.0 6.1 0.0 79.8 77.0 31.6 .24.0 26.2 25.0 32.6 30.0 0.67 0.60 0.13 0.10 Variable BUN Creatinine Glucose Cholesterol LDL HDL Triglycerides Hematocrit Hemoglobin RBC MCH MCHC mcv WBC Platelets Mean 15.9 1.0 86.7 215.9 136.6 48.5 151.0 46.3 15.3 4.9 31.1 33.1 93.7 6.9 226.4 Median 15.0 1.0 85.0 214.0 134.0 48.0 126.0 47.0 15.3 4.9 31.0 33.0 94.0 6.6 223.0 Std Dev 3.8 0.2 18.8 42.5 39.1 12.7 99.9 2.7 0.9 0.3 1.5 0.7 4.9 1.9 45.4 Ranpc Table 2 (Continued) 8-26 0.6-1.6 60-260 100-340 28-261 .23-94 34-651 38.3-52.0 13-17.4 4.0-5.74 26.0-36.9 31.3-34.7 79.7-114.6 3.6-15.5 122-367 Mean 14.4 0.9 90.7 211.2 135.3 45.5 156.5 45.8 15.4 5.1 30.5 33.6 90.7 6.5 225.7 Median St 14.0 0.9 86.0 213.0 135.0 45.0 122.0 46.0 15.5 4.8 31.0 34.0 91.0 6.2 230.0 Table 3 Mean Values of PFOS, Demographic,Serum Chemistryand Hematologic ParametersforAntwerp and Decatur,1995 and 1997 Examinations Variable PFOS(ppm) 1995 Data AntweEp Decatur 1.93 2.44 1997 Data Antwerp Decatur 1.48 1.96 Age 37*** 45 33*** 44 BNU 23.9*** 29.2 23.5*** 30.0 Cigarettes Alcohol 4.7* 7.9 1.3*** 0.2 5.5 6.6 1.1*** 0.1 Alk Phosphatase 75*** 97 70*** 87 GGT 41 48 26* 36 AST 26* 29 27 26 ALT 44 47 31 34 Totalbilirubin 0.86*** 0.58 0.80*** 0.58 Directbilirubin 0.22 0.21 0.15*** 0.12 BUN Creatinine 17.0*** 14.8 0.9*** 1.1 14.9 14.1 0.9** 1.0 Glucose 81*** 92 81*** 98 Cholesterol 214 218 206 215 LDL 138 136 134 137 HDL 54*** 43 Triglycerides 115*** 187 50*** 42 111*** 192 Table 3 (continued) Variable 1995 Data AntweER Decatur Hematocrit 47*** 46 Hemoglobin 15.4 15.2 RBC 4.9 5.0 MCH 31.4*** 30.7 MCHC 32.9*** 33.4 NWC 95.7*** 91.8 WBC 6.4*** 7.5 Platelets p <.05; 224 229 p <.Ol; ***p<.001 1997 Data AntweEp Decatur 46* 45 15.4 15.3 5.1 5.1 30.5 30.4 33.3*** 33.7 91.6* 90.0 6.5 6.4 237* 217 Table 4 CorrelatioCnoefficientBsetween PFOS and SelectedVariablesby Locationand Year of Examin Variable Age Alcohol BMI Cigarettes BUN Creatinine 1995 Data Both Locations Antwerp .12 .10 .09 .25* .01 -.14 .14 .19 -.05 -.04 .05 -.37 Decatur .04 .06 -.05 .08 .01 .28** 1997 Data Both Locations Antweip .20 .41 .10 .40* .18* .22 -.03 .08 .01 .13 .08 -.12 Glucose -.02 -.17 -.02 .10 .04 AlkalinePhosphatase .06 .07 -.06 .07 .09 GGT .01 .02 -.04 AST .06 .06 .0002 .07 .26 .003 .03 Variable ALT 1995 Data Both Locations AntweEp -.01 -.03 TotalBilirubin -.15* -.13 DirectBilirubin -.03 -.13 Cholesterol -.02 .02 LDL .01 .02 HDL 17* -.14 Triglycerides .04 .11 Hematocrit .002 .10 Hemoglobin -.01 .05 Red Blood Cells -.03 -.I 1 MCH .04 .21* Table 4 (continued) Decatur -.03 1997 Data Both Locations Antwe!p .16* .11 -.07 -.13 -.12 .09 -.18 -.13 -.08 .25** .34** .02 .22** .30* -.12 -.07 -.05 -.10 .10 .39*** -.0003 -.16* -.05 -.02 -.15 -.05 .01 -.11 -.15 -.04 -.04 .17 Variable MCHC 1995 Data Both Locations Antwerp -.03 -.11 mcv .05 .25* White Blood Cells .18* .27** Platelets 15* -.06 p<.05; **p<.Ol; p <.001 Table4 (continued) Decatur -.09 1997 Data Both Locations Antwerp .01 -.03 -.01 -.03 .20 .04 .01 .18 -.25* 11 -.06 Table 5 Mean, Median, StandardDeviation(SD) of Mean and Range of PFOS, Demographic,Serum Chemistriesan forAntwerp and DecaturEmployees Combined, 1995 (N=178) and 1997 (N=147) PFOS* (ppm) Mean 1995 Data Median SD Range 1997 D Mean Median 0 -< Ippm 1 -< 3ppm 3 - < 6ppm 6ppm 0.49' 0.5 0.27 1.82' 1.77 0.58 4.12' 3.97 0.81 8.17' 7.73 2.52 F value 321.9,p <'.0001 PFOS(ppm) 000-0.90 1.00-2.91 3.00-5.80 6.06-12.83 0.52' 1.78' 3.87' 7.20' F value 0.52 1.64 3.'59 6.68 367.6,p <.0001 0 -< Ippm 37 36 8 1 - < 3 ppm 42' 41 9 3 - < 6 ppm 40 40 7 6 ppm 45 43 7 F value= 3.7,p = .02 Age (yrs) 21-58 25-60 26-55 37-56 36 34 42' 41 41 42 42 45 F value= 5.1,p = .002 PFOS (ppm) 0 -< lppm I -< 3 ppm 3 -< 6 ppm 6ppm 0-< Ippm 1-<3ppm 3 - < 6 ppm > 6 ppm 0 -< Ippm I-< 3 ppm 3 - < 6 ppm 6 ppm 1995 Data Mean Median SD 0.8 0.6 0.9 0.5 0.1 0.7 1.2 0.3 1.9 0.7 0.0 1.1 F value 4.0,p .009 Table5 (continued) 1997 Data Range Mean Median Alcohol(drinks/day) 0.0 3.6 0.0-3.6 0.0-6.0 0.0-2.9 0.5 0.5 1.0 0.2 F value 0.1 0.1 0.1 0.1 1.8,p =.15 25.5 24.8 27.7 26.3 24 .93 25.0 27.7 29.4 F value 3.7,p .0@ BMI (k m') 4.2 17.9-38.7 5.8 19.6-60.7 3.8 17.9-32.5 4.2 20.6-33.0 26.0 27.7 27.3 30.8 F value 24.9 26.4 27.9 29.7 2.1,p =.10 2.6 6.8 10.6 0.4 F value 0.0 0.0 8.0 0.0 4.8,p =.003 Cigarette(sperday) 6.4 0.0-25.0 11.3 0.0-40.0 12.4 0.0-40.0 1.1 0.0-3.0 4.7 0.0 8.2 0.0 4.1 0.0 6.0 0.0 F value= 1.5,p .23 1995 Data PFOS (ppm) Mean Median SD 0 -< Ippm 1 - <3 ppm 3 - < 6 ppm 6 ppm 16.5 15 3.5 15.4 15.0 4.0 16.4 16.0 3.7 15.1 14.0 4.2 F value 1.1,p = .36 0 -< Ippm 1 - <3 ppm 3 - < 6 ppm 6 ppm 1.0 1.0 0.2 1.0 1.0 0.2 0.9 0.9 0.2 1.1 1.2 - 0.3 F value 2.3,p = .08 0 -< I ppm 1 - <3 ppm 3 - < 6 ppm 6 ppm 85 85 15 86 86 22 84 83 12 84 83 14 F value= 0.9,p =.44 Table5 (continued) Range 1997 Dat Mean Median BUN 11 -26 8.0-26.0 10.0-23.0 10.0-21.0 14.5 14.2 15.0 13.8 F value 0.5,p 14.0 14.0 15.0 12.0 0.67 Creatinine 0.7-1.6 0.7-1.6 0.7-1.2 0.6-1.6 0.9 0.9 0.9 1.0 F value 0.4,p 0,9 0.9 0.9 0.9 0.78 Glucose 66-170 60-260 66-114 71-105 87 93 95 89 F value 0.6,p 85 84 89 88 .59 PFOS --Ppm) 0-< I ppm 1 - <3 ppm 3 - < 6 ppm 6 ppm 0 -< Ippm 1 - <3 ppm 3 - < 6 ppm @t6 ppm 0 -< Ippm 1-<3ppm 3-<6ppm 6 ppm Table5 (continued) 1995 Data 1997 D Mean Median SD Range Mean Median 80 78 89 89 86 85 88 85 F value 1.3,p .28 AlkalinePhosphatase 22 31-158 77 73 27 49-191 83 79 21 32-124 76 74 24 63-136 88 84 F value 1.17, p .32 43 47 40 43 F value 31 36 39 33 0.5,p =.71 GGT 28 16-155 28 22 39 2-293 36 25 15 21-80 28 27 18 28-79 33 37 F value 1.1,p = .34 27 25 29 26 25 24 33 33 F value- 1.8,p 14 AST 13 15-96 27 25 12 14-90 26 25 5 13-37 25 23 6 26-43 29 28 F value 0.5,p =.67 PFOS (ppm) 0 - < 1 ppm 1 - <3 ppm 3 - < 6 ppm @t6 ppm 0 -< I ppm 1 - <3 ppm 3 -< 6 ppm 6 ppm 0 -< Ippm I -<3 ppm 3 -< 6 ppm 6 ppm Table5 (continued) 1995 Data 1997 D Mean Median SD Range Mean Median 48 46 42 51 F value 43 42 41 49 1.0,p =.38 ALT 20 27-118 31 30 21 18-183 33 29 7 30-59 34 31 17 29-82 41 45 F value 0.9,p =.46 0.88 0.66' 0.64' 0.76 F value 4.4,p 0.70 0.60 0.60 0.70 .005 TotalBilirubin 0.50 0.40-2.90 0.77 0.60 0.30 0.20-1.50 0.61' 0.60 0.28 0.20-1.40 0.63 0.50 0.23 0.50-1.20 0.58 0.50 F value 2,9,p .04 0.22 0.20 0.21 0.20 0.21 0.20 0.20 0.20 F value= 0.6,p =.58 DirectBilirubin 0.05 0.02-0.40 0.15 0.10 0.06 0.10-0.40 0.12' 0.10 0.04 0.20-0.30 0.12 0.10 0.02 0.100.30 0.10 0.10 F value= 3.5,p =.02 PFOS (ppm) 0 - <1 ppm 1 -<3 ppm 3 - <6 ppm 2!6 ppm 0 - <1 ppm 1 -<3ppm 3 - <6 ppm 2t6 ppm 0 -<1 ppm I-<3 ppm 3 - <6 ppm @t6 ppm 0 -<1 ppm I-<3 ppm 3 - <6 ppm 6 ppm 1995 Data Mean Median SD 219 215 47 216 213 43 214 214 35 213 221 36 F value 0.1,p =.96 Table5 (continued) 1997 Da Range Mean Median Cholesterol 100-340 118-315 128-278 160-251 198 197 216 219 229' 224 229 238 F value= 4.3,p =.006 140 134 137 142 F value 137 134 135 136 0.2,p =.87 53 48 45 45 F value 53 47 46 46 2.9,p =.04 129 96 161 133 158 142 132 151 F value= 1.1,p =.35 LDL 43 29-261 124 128 40 44-234 141 134 34 65-190 148' 142 32 95-178 145 156 F value= 3.7,p =.Ol HDL 13 31-94 46 48 13 26-94 44 45 11 23-74 48 47 9 34-61 40 38 F value= 1.1,p =.34 Ttip,lycerides 98 41-622 107 41-651 88 34-413 45 64-187 148 107 156 122 166. 158 220 191 F value= 0.5,p =.67 PFOS (ppm) 0 - <1 ppm 1 - <3 ppm 3 -<6 ppm > 6 ppm 0 -<1 ppm 1 -<3 ppm 3 -<6 ppm 6 ppm 0 - <1 ppm 1 -<3 ppm 3 -<6 ppm 6 ppm 1995 Data Mean Median SD 47 47 2 46 46 3 47 47 2 47 48 2 F value 2.4,p =.07 Table5 (continued) 1997 E Range Mean Median Hematocrit 43-51 38-52 41-52 44-49 46 45 46 45 F value 46 46 44 44 2.1,p =.I I 15.5 15.2 15.5 15.5 F value 15.5 15.2 15.5 15.4 2.2,p =.10 5.0 5.0 4.9 4.9 5.0 5.o 5.0 4.9 F value=0.4,p = .75 Hemoglobin 0.7 14.0-16.7 15.5 15.5 1.0 13.0-17.4 15.4 15.5 0.8 13.6-17.4 15.0 14.7 0.7 14.7-16.2 15.1 15.0 F value 1.8,p 15 RBC 0.3 4.3-5.7 5.1 5.2 0.3 4.3-5.7 5.0 5.1 0.2 4.6-5.5 5.0 5.0 0.5 4.0-5.7 5.0 4.9 F value= 1.4,p = .25 PFOS (ppm) 0 - <1 ppm 1 -<3 ppm 3 - <6 ppm @ 6 ppm 0 - <1 ppm 1 -<3 ppm 3 - <6 ppm 6 ppm 0 -<1 ppm 1 - <3 ppm 3 - <6 ppm @t6 ppm 1995 Data Mean Median SD 31.3 31.2 1.6 30.9 30.9 1.4 31.2 31.3 1.5 31.2 30.5 2.8 F value 0.9,p =.45 Table5 (continued) 1997 D Range Mean Median MCH 27.7-34.3 26.4-34.3 26.0-33.6 28.2-36.9 30.4 30.3 30.6 30.5 30.2 31.2 30.5 30.5 F value= 0.6,p .65 33.1 33.2 33.2 33.1 33.1 32.6 33.1 33.3 F value= 0.2,p = .90 94 95 93 94 94 94 94 92 F value= 1.1,p =.35 MCHC 0.7 31.9-34.7 33.6 33.6 0.6 31.7-34.5 33.6 33.6 0.7 31.3-34.3 33.5 33.5 0.6 32.2-34.0 33.9 33.9 F value 0.7,p =.56 mcv 5.2 85-106 4.3 80-104 4.8 81-104 9.7 85-115 90 90 91 91 90 91 90 91 F value= 0.6,p =.59 PFOS (ppm) Mean 1995 Data Median SD Table5 (continued) Range Mean 1997 D Median 0 -<1 ppm 1 -<3 ppm 3 -<6 ppm 2:6 ppm 6.1 6.0 7.0' 6.8 7.6' 6.9 7.0 6.9 F value= 4.3,p =.006 WBC 1.3 4.1-9.4 2.0 3.6-15.5 2.2 4.1-13.3 0.6 6.4-7.8 6.1 6.9 6.2 6.2 F value 5.8 6.6 6.1 7.1 2.2,p =.09 0 - <1 ppm I-<3 ppm 3 - <6 ppm 6 ppm 226 224 229 224 228 226 185 182 F value= 2.1,p =.10 Platelets 40 159-309 47 122-367 45 132-344 50 132-277 227 229 220 199 F value 0.6,p 220 223 221 191 0.60 1.Mean issignificantdliyfferen(tp<.05,Bonferroni(Dunn) testt)hanthemean oftheotherPFOS categories. 2. Mean issignificantdliyfferen(tp<.05,Bonferroni(Dunn)testt)hanthemean of0 -< I ppm PFOS category. 3. Mean issignificantdliyfferen(tp<.05,Bonfeffoni(Dunn)testt)hanthemean of I -< 3 ppm category. Sample Size 0 -<1 ppm 1 - <3 ppm 3 -<6 ppm 2:6 ppm 1995 Data 45 91 35 7 1997 Data 60 63 21 5 Table 6 Mean, Median (Med),StandardDeviation(SD) ofMean and Range of PFOS, Demographic, Serum Chemistriesand HematologicalValues by PlantLocation,1995 PFOS* (I)R Antwerp Mean Med SD Range 1995 Data Mean Decatur Med SD Range 0 <1 1 <3 3 <6 >6 PFOS 0.46' 0.45 0.29 0.00-0.90 0.60' 0.63 0.19 0.25-0.88 1.69' 1.50 0.57 1.00-2.90 1.89' 1.89 0.58 1.00-2.91 3.96' 3.70 0.79 3.00-5.60 4.31' 4.23 0.82 3.11-5.80 8.171 8.50 1.92 6.10-9.90 8.17' 6.90 3.20 6.06-12.83 F value= 241.0,p =.0001 F value= 114.5,p = .0001 0 <1 1 <3 3 <6 >6 Age 36 36 7 21-52 40 39 11 29-58 36 34 9 25-60 46 46 7 30-58 37 37 7 28-51 44 44 7 26-55 40 37 6 37-47 48 47 7 42-56 F value= 0.5,p =.71 F value= 2.0,p =.12 0 <1 1 <3 3 <6 >6 1.0 0.7 1.0 1.0 0.8 0.9 2.0 1.3 2.2 1.7 1.4 1.1 F value= 2.9,p Alcohol 0.0-3.6 0.1 0.0 0.0-3.6 0.2 0.0 0.0-6.0 0.4 0.0 @0.7- 2.9 0.0 0.0 .04 F value= 0.3 0.0-0.9 0.4 0.0-2.0 0.9 0.0-3.4 0.0 0.0-0.1 1.1,p =.37 0 <1 1 <3 3 <6 >6 BMI 24.1 24.3 2.4 17.9-28.1 24.3 23.8 2.4 19.6-31.6 23.1 23.0 3.3 17.9-31.4 23.7 24.7 2.8 20.6-25.8 F value= 0.9, p =.47 30.1 28.0 5.3 29.6 28.3 6.2 27.0 27.5 3.4 30.7 30.2 1.6 F value= 1.1,p = .35 22.8-38.7 22.3-60.7 19.1-32.5 29.4-33.0 PFOS (PRM) 0 <1 1 <3 3 <6 >6 0 <1 1 <3 3 <6 >6 0 <1 1 <3 3 <6 >6 0 <1 1 <3 3 <6 >6 AntwerR Mean Med SD Table 6 (continued) Range Decatur Mean Med SD Range 3.0 0.0 4.1 0.0 9.13 7.5 1.0 0.0 F= 3.1, p 7.0 7.0 9.0 1.7 .03 Cigarettes 0-25 1.4 0.0 3.8 0-23 8.3 0.0 12.9 0-25 12.5 0.0 15.7 0-3 0 0.0 0 F value= 2.3,p = .09 0-13 0-40 0-40 0-0 75 75 16 73 66 19 79 78 20 74 74 11 F value = 0.5,p =.69 AlkalinePhoRhatase 31-104 96 99 29 49-108 98 95 27 32-12195 95 96 18 63-85 98 91 27 F value= 0.1,p = .98 47-158 49-191 58-124. 73-136 39 29 22 48 30 58 34 34 11 31 32 3 F value= 0.7, p =.55 GGT 16-111 12-293 21-55 28-33 55 41 41 46 40 24 47 48 16 52 49 20 F value= 0.5,p = .71 21-155 2-118 21-80 30-79 AST 26 23 13 15-96 27 26 14 14-90 23 22 5 13-35 33 35 6 26-37 F value= 0.9, p =.45 32 31 9 29 27 10 27 26 5 34 32 7 F value= 0.9,p =.44 19-52 17-85 21-37 28-43 PFOS (ppm) 0 <1 1 <3 3 <6 >6 0 <1 1 <3 3 <6 >6 0 <1 1 <3 3 <6 >6 0 <1 1 <3 3 <6 >6 0 <1 1 <3 3 <6 >6 Table 6 (continued) AntweER Mean Med SD Range Decatur Mean Med SD Range ALT 46 42 18 27-108 45 40 18 26-122 40 39 6 30-52 50 38 28 29-82 F value= 0.7,p =.59 55 47 24 47 42 22 43 42 9 52 53 8 F value= 0.8, p =.49 37-118 18-183 30-59 41-59 0.96 0.80 0.55 0.83. 0.80 0.26 0.75 0.70 0.30 0.93 0.90 0.25 F value = 1.2,p =.31 TotalBilirubin 0.40-2.90 0.65 0.60 0.16 0.40-1.30 0.57 0.50 0.28 0.30-1.40 0.51 0.50 0.18 0.70-1.20 0.63 0.65 0.10 F value= 0.7, p =.54 0.40-0.90 0.20-1.50 0.20-1.00 0.50-0.70 0.23 0.20 0.06 0.22 0.20 0.04 0.21 0.20 0.03 0.20 0.20 0.00 F value= 0.7,p =.55 DirectBilirubin 0.20-0.40 0.20 0.20 0.00 0.20-0.30 0.20 0.20 0.06 0.20-0.30 0.20 0.20 0.04 0.20-0.20 0.20 0.20 0.08 F value= 0.4,p =.74 0.20-0.20 0.10-0.40 0.20-0.30 0.10-0.30 17.0 17.0 3.6 16.7 16.0 3.8 17.3 17.0 3.8 17.3 21.0 6.4 F value = 0.1,p = .95 BUN 12.0-26.0 14.8 15.0 2.7 11.0-26.0 14.7 14.0 4.0 10.0-23.0 15.2 15.0 3.1 10.0-21.0 13.5 13.5 0.06 F value= 0.2,p = .87 11.0-21.0 8.0-24.0 10.0-23.0 13.0-14.0 Creatinine 1.0 0.9 0.2 0.8-1.6 1.1 1.1 0.2 0.7-1.3 0.9 0.9 0.1 0.7-1.1 0.93 0.9 0.1 0.7-1.0 1.1 1.1 0.2 0.9-1.6 1.1 1.1 0.1 0.8-1.2 0.8 0.8 0.2 0.6-0.9 1.3 1.3 0.2 1.2-1.6 F value= 4.7,p = .004 F value= 3.8,p = .01 PFOS (R]2m) 0 <1 1 <3 3 <6 >6 0 <1 1 <3 3 <6 >6 0 <1 1 <3 3 <6 >6 0 <1 1 <3 3 <6 >6 0 <1 1 <3 3 <6 >6 Table 6 (continued) Antwelp Mean Med SD Range Decatur Mean Med SD Range 83 83 8 82 81 13 80 82 9 72 72 2 F value= 1.3,p =.29 Glucose 66-103 90 86 28 60-126 93 89 25 66-101 89 89 14 71-74 93 92 12 F value = 0.1,p = .94 66-170 67-260 66-114 83-105 220 219 50 206 211 49 217 215 30 223 221 16 F value= 0.6,p =.61 Cholesterol 100-340 215 208 39 118-315 221 218 39 178-266 209 213 42 208-240 206 206 47 F value= 0.5,p =.69 154-276 132-300 128-278 160-251 140 138 45 131 124 46 143 139 27 144 136 20 F value= 0.4,p =.76 LDL 29-261 44-220 99-189 130-168 139 130 38 136 136 36 131 128 41 139 142 42 F value = 0.1, p =.94 79-192 62-234 65-190 95-178 HDL 56 57 13 31-94 43 41 9 53 51 13 33-79 45 44 12 50 49 11 31-74 39 39 9 53 49 7 48-61 39 39 5 F value = 1.1, p =.35 F value= 1.4,p=.25 31-59 26-94 23-51 34-46 117 93 98 105 75 65 126 112 64 129 116 52 F value= 0.3,p =.81 Triglycerides 41-622 167 151 94 41-368 191 146 114 34-278 199 198 99 85-187 135 153 48 F value= 0.5,p =.67 62-307 61-651 78-413 64-168 PFOS (12vm) 0 <1 1 <3 3 <6 >6 0 <1 1 <3 3 <6 >6 0 <1 1 <3 3 <6 >6 0 <1 1 <3 3 <6 >6 0 <1 1 <3 3 <6 >6 Table 6 (continued) AntweER Mean Med SD RanLe Decatur Mean Med SD Range Hematocrit 47 47 2 43-51 46 45 2 46 47 2 42 -51 45 45 3 48 47 2 44-51 46 46 3 47 48 1 46-48 46 46 2 F value= 1.5,p = 23. F value= 0.3, p =.83 43-50 38-52 41-52 44-49 15.5 15.5 0.8 15.2 15.3 0.7 15.6 15.6 0.5 15.4 15.4 0.6 F value= 1.4,p =.26 Hemoglobin 14.0-16.7 15.5 15.4 0.7 13.8-16.6 15.1 15.1 1.1 14.6-16.7 15.3 15.3 1.0 14.8-16.0 15.5 15.6 0.8 F value= 0.7, p =.58 14.5-16.4 13.0-17.4 13.6-17.4 14.7- 16.2 RBC 4.9 5.0 0.3 4.3-5.7 5.1 5.1 0.2 4.9 4.9 0.2 4.3-5.4 4.9 4.9 0.3 5.0 5.0 0.2 4.7-5.3 5.0 4.9 0.3 4.7 4.9 0.6 4.0-5.2 5.2 5.1 0.4 F value= 0.9,p =.46 F value= 1.1,p = .35 4.8-5.5 4.3-5.7 4.6-5.5 4.8-5.7 MCH 31.5 31.3 1.5 27.7-34.3 31.2 31.0 1.2 29.5-34.3 31.5 31.9 1.2 29.1-33.3 33.0 32.5 3.7 29.6-36.9 F value= 1.4,p =.25 30.7 30.7 1.6 30.7 30.9 1.5 30.9 31.2 1.7 29.9 30.4 1.2 F value= 0.4,p =.74 28.7-33.5 26.4-33.1 26.0-33.6 28.2-30.7 32.9 33.0 0.6 32.9 32.8 0.6 32.8 32.7 0.7 32.6 32.4 0.5 F value= 0.4, p =.78 MCHC 31.9-34.5 31.7-33.8 31.3-34.2 32.2-33.1 33.8 33.9 0.6 33.3 33.3 0.5 33.4 33.4 0.6 33.5 33.4 0.3 F value= 2.2, p=.10 32.9-34.7 31.9-34.5 32.1-34.3 33.3-34.0 PFOS (ppm) 0 <1 1 <3 3 <6 >6 Table 6 (continued) AntweEp Mean Med SD Range Decatur Mean Med SD Range 96 96 5 95 95 3 96 97 4 101 98 12 F value= 1.8,p =.16 mcv 85-106 90 - 10* 88-104 91-115 91 90 4 92 93 4 92 92 5 89 90 3 F value= 0.8,p =.50 85-99 80-100 81-101 85-92 0 <1 1 <3 3 <6 >6 WBC 5.9 5.7 1.3 4.1-9.4 6.8 6.9 1.1 6.1 6.1 1.3 3.8-8.8 7.5 7.0 2.2 7.5' 6.9 2.5 4.1-13.3 7.7 7.4 1.9 6.5 6.4 0.2 6.4-6.7 7.4 7.4 0.4 F value= 4.5, p = .006 F value= 0.5, p =.72 5.0-9.0 3.6-15.5 4.9-11.5 6.9-7.8 0 <1 1 <3 3 <6 >6 224 222 42 222 220 41 237 4 234 52 162 151 36 F value= 2.6, p =.06 Platelets 159-309 233 246 35 153-318 233 225 50 132-344 218 214 34 132-202 202 194 56 F value= 1.0,R =.40 162-271 122-367 172-287 143-277 *Sample sizes: FC95 Level Antwelp 0 < Ippm 34 1 < 3 ppm 32 3 < 6 ppm 19 2!6 ppm 3 88 Decatur 11 59 16 4 90 1. Significantdliyfferen(tp<.05, Bonferroni(Dunn) t-testt)hantheremainingthreePFOS exposure categories. 2. Significantdliyfferen(tp< .05,Bonferroni(Dunn) t-testt)hanthe0 -< I ppm and theI < 3 ppm categories. 3. Significantdliyfferen(tp<.05,Bonfeffoni(Dunn) t-testt)hanthe0 - < I ppm category. 4. Significantldyifferen(tp < .05,Bonfeffoni(Dunn) t-testt)hanthe 3 -< 6 ppm category. Table 7 Mean, Median (Med), StandardDeviation(SD) ofMean and Range of PFOS, Demographic, Serum Chemistriesand HematologicalValues by PlantLocation,1997 PFOS* AntwerR Mean Med SD 1997 Data Range Mean Decatur Med SD Range 0 -< 1 I-< 3 3 -< 6 >6 PFOS 0.46' 0.37 0.27 0.10-0.94 0.60' 0.59 0.26 0.10-0.97 1.89' 1.79 0.61 1.02-2.89 1.71' 1.53 0.52 1.04-2.85 3.87' 3.66 0.59 3.22-4.83 3.87' 3.51 0.81 3.09-5.30 - - - - 7.20' 6.68 1.59 6.05-9.93 F value = 195.3,p = .0001 Fvalue=218.1, p=.0001 0 -< 1 1-< 3 3 -< 6 >6 0 -< 1 1-< 3 3 -< 6 >6 0 -< 1 1-< 3 3 -< 6 >6 Age 29 28 6 37 3 37 9 37 3 37 3 - - - 21-50 24-63 32-40 - 43 44 9 45 45 8 45 44 4 42 45 9 23-62 31-62 36-54 29-52 F value = 10.4,p = .0001 F value = 0.5, p =.69 Alcohol 0.8 0.5 1.0 0.0-4.3 0.2 0.1 0.4 0.1-2.0 1.0 0.7 1.1 0.0-5.0 2.23 1.4 2.3 0.0-7.1 0.1 0.1 0.1 0.1-0.3 0.1 0.1 0.1 0.1-0.3 - - - 0.2 0.1 0.3 0.1-0.8 F value = 4.3, p =.02 F value = 0.8, p =.49 22.9 21.9 2.1 24.2 23.9 2.8 23.6 24.9 3.1 - - - F value = 2.0,p =.15 BNU 20.2-28.3 29.3 28.9 4.9 18.1-30.4 30.0 29.0 6.0 19.2-28.3 30.0 29.3 3.0 30.8 29.7 4.0 F value= 0.2,p =.91 22.4-41.7 20.2-48.5 25.4-36.0 26.1-36.2 PFOS ipp-M) 0 -< 1 1 -< 3 3-<6 >6 0 -< 1 1-< 3 3 -< 6 >6 0 -< 1 1-< 3 3 -< 6 >6 0 -< 1 1-< 3 3 -< 6 >6 Table 7 (continued) AntweIR Mean Med SD Range Decatur Mean Med SD Range 4.2 0.0 7.3 2.0 5 0.0 - - F = 1.3,p 6.7 8.1 7.8 - .28 Ci,earettes 0-20 5.3 0.0 11.6 0-40 0-20 8.7 0.0 13.0 0-40 0-20 3.3 0.0 9.0 0-30 - 6.0 0.0 13.4 0-30 F value= 0.8,p =.51 AlkalinePhOsRhatase 69 68 14 49-110 86 84 16 55-132 74 74 16 41-113 88 83 26 41-163 64 59 24 29-120 - -- - 85 83 15 61-109 88 84 18 65-114 F value= 1.5,p =.22 F value= 0.1,p = .96 GGT 21 17 10 10-50 34 24 34 10-144 25 22 10 14-43 - - - - F value= 2.5,p .09 36 32 25 37 27 33 31 28 15 33 37 12 F value= 0.2,p =.91 13-142 13-179 13-71 17-48 AST 27 26 7 27 25 7 25 24 4 - - 17-53 15-48 19-30 - F value= 0.2,p =.80 26 25 7 13-48 26 25 7 18-56 25 23 9 14-43 29 28 3 26-34 F value= 0.4,p = .77 PFOS (R]2 0 -< 1 I-< 3 3-<6 >6 0 -< 1 1-< 3 3 -< 6 >6 0 -< 1 1-< 3 3 -< 6 >6 0 -< 1 1-< 3 3 -< 6 >6 0 -< 1 1-< 3 3-<6 >6 Table 7 (continued) AntweER Mean Med SD Range Decatur Mean Med SD Range ALT 30 25 12 13-60 33 31 16 13-87 28 23 10 14-46 - -- - F value= 0.6,p = .58 33 31 11 33 28 16 38 33 21 41 45 10 F value= 0.9,p =.45 17-57 10-89 17-82 25-49 TotalBilirubin 0.90 0.80 0.46 0.40-2.30 0.63 0.60 0.30 0.30-1.40 0.68 0.70 0.23 0.30- 1.30 0.56 0.50 0.18 0.30-1.00 0.79 0.70 0.40 0.30- 1.30 0.51 0.50 0.16 0.30-0.90 - -- - 0.58 0.50 0.24 0.40-1.00 F value= 2.3,p = .11 F value= 1.0,p = .41 DirectBilirubin 0.16 0.20 0.08 0.10-0.40 0.13 0.10 0.06 0.10-0.30 0.13 0.10 0.05 0.10 - 0.20 0.11 0.10 0.03 0.10-0.20 0.14 0.10 0.05 0.10- 0.20 - - 0.11 0.10 0.03 0.10-0.20 0.10 0.10 0.00 0.10-0.10 F value= 2.2,p =.12 F value= 1.3,p =.28 14.3 14.0 2.1 BLTN 11.0-19.0 15.2 15.0 2.6 16.0 16.0 2.7 - -- 10.0-20.0 12.0-20.0 F value= 2.1, p =.13 14.7 14.0 3.3 9.0-21.0 13.5 13.5 3.5 6.0-26.0 14.3 14.0 3.0 9.0-19.0 13.8 12.0 4.1 9.0-19.0 F value= 0.7,p =.56 Creatinine 0.9 0.9 0.1 0.7-1.2 1.0 1.0 0.1 0.9 0.9 0.1 0.7-1.3 1.0 1.0 0.1 0.9 0.9 0.1 0.8-1.1 - -- 1.0 1.0 0.1 1.0 0.9 0.2 F value= 0.3,p = .76 F value= 0.2,p =.89 0.6-1.2 0.7-1.3 0.7-1.1 0.8-1.4 PFOS (12R 0 -< 1 1 -< 3 3 -< 6 >6 0 -< 1 1-< 3 3 -< 6 >6 0 -< 1 1-< 3 -3-<6 >6 0 -< 1 1-< 3 3 -< 6 >6 0 -< 1 1-< 3 3-< 6 >6 Table 7 (continued) Antwerp Mean Med SD Ran&e Decatur Mean Med SD Range 81 82 10 79 78 9 84 85 8 - -- F value= 0.8,p =.47 Glucose 63-114 93 91 21 65 - lo@ 102 89 47 74-96 - 103 93 30 89 88 7 F value= 0.5,p = 58-174 75-303 79-192 80-97 .67 193 190 41 213 205 48 228 223 38 - -- F value= 2.9,p =.07 Cholesterol 110-277 204 208 38 145-277 116-365 218 226 39 152-290 192-321 - 230 230 23 229 238 26 197-280 186-250 F value= 2.0,p =.13 122 114 35 143 134 42 LDL 57-205 67-290 147 141 24 - -- 111-195 - F value= 3.0,p =.06 127 133 33 139 135 35 149 144 25 145 156 26 F value= 1.6,p =.19 50-178 61-196 113-196 103-164 HDL 51 50 12 19-74 48 46 10 34-68 51 50 10 39-69 - - - - F value= 0.8,p =.47 42 41 9 42 41 10 45 45 10 40 38 4 F value= 0.5,p =.67 26-59 28-69 32-62 37-45 Tiijzlycerides 99 92 41 38-175 200 128 219 46-1209 112 95 58 44-290 185 147 124 63-534 150 122 88 - -- 65-362 179 183 98 220 191 83 45-394 149-352 F value= 2.9,p =.06 F value= 0.1,p = .95 PFOS (RR 0 -< 1 1-< 3 3 -< 6 >6 0 -< 1 1-< 3 3 -< 6 >6 0 -< 1 1-< 3 3-<6 >6 0-< 1 1-< 3 3 -< 6 >6 0 -< 1 1-< 3 3 -< 6 >6 Table 7 (continued) AntweM Mean Med SD Range Decatur Mean Med SD ---Ranae Hematocrit 47 47 3 42-52 46 45 2 40-50 46 47 3 40-53 46 46 3 39-51 46 45 3 42-50 - -- - 44 44 2 45 44 2 39-48 42-47 F value= 0.7,p =.51 F value= 1.6,p =.18 Hemoglobin 15.6 15.5 0.8 14.2-17.0 15.4 15.4 0.7 13.5-16.9 15.4 15.6 1.0 13.3-17.3 15.4 15.5 0.9 13.5-17.3 15.2 14.7 1.0 14.0-16.7 14.8 14.7 1.0 12.5-16.5 - -- 15.1 15.0 0.8 14.1-16.2 F value= 0.7,p =.48 F value= 1.7,p =.18 RBC 5.1 5.2 0.4 4.6-5.9 5.1 5.1 0.3 4.3-5.7 5.0 5.1 0.3 4.1-5.5 5.1 5.1 0.3 4.2-5.5 4.9 4.8 0.4 4.4-5.7 5.0 5.0 0.3 4.5-5.4 - -- 5.0 4.9 0.3 4.7-5.5 F value= 1.7,p =.19 F value= 0.4,p =.78 MCH 30.4 30.4 1.3 27.9-33.5 30.3 30.2 1.8 27.6-34.1 30.6 30.5 0.9 29.2-32.8 30.6 30.6 1.4 26.7-33.8 30.9 31.4 1.4 - -- 28.8-32.7 29.7 30.5 2.2 30.5 30.5 2.1 26.2-32.9 27.5-33.4 F value= 0.9,p =.40 F value= 1.0,p = .41 MCHC 33.4 33.4 0.5 32.2-34.0 33.8 33.3 33.2 0.5 31.8-34.1 33.8 33.4 33.5 0.5 32.4-34.3 33.6 - -- 33.9 F value= 0.6,p = .54 33.7 0.5 32.8-34.9 33.8 0.5 32.7-34.6 33.9 0.8 32.0-34.4 33.9 0.5 33.4-34.6 F value= 0.6,p =.62 PFOS (ppm) 0 -< 1 1-< 3 3 -< 6 >6 Table 7 (continued) Antwerp Mean Med SD Range Decatur Mean Med SD Range mcv 91 91 4 84-101 92 92 3 87-99 93 95 5 - -- 86-97 - F value= 1.3,p =.29 90 89 5 91 90 4 88 89 5 90 91 6 F value= 0.9,p =.45 83-101 81-99 80-96 81-96 0 -< 1 1-< 3 3 -< 6 >6 WBC 6.0 5.7 1.3 3.8-8.8 7.1 6.8 2.2 4.4-13.2 6.4 6.0 1.8 4.2-10.0 - - - F value= 2.6,p = .08 6.3 5.9 1.6 6.7 6.6 1.6 6.1 6.1 1.3 6.2 7.1 1.5 F value= 0.8,p =.51 4.0-10.3 3.8-10.1 4.0-8.9 4.2-7.4 0 -< 1 1 -< 3 3-<6 >6 Platelets 237 232 55 126-406 215 207 50 106-363 243 232 48 151-359 219 210 48 124-323 215 225 41 - - - 147-263 - 224 219 50 199 191 58 159-316 146-295 F value= 1.1.R = .35 F value= 0.3.p =.80 *Sample sizes: FC95 Level Antwerp 0 -< I ppm 31 1 -< 3 ppm 25 3 -< 6 ppm 9 2:6 ppm 0 65 Decatur 29 38 12 5 84 1. Significantdliyfferen(tp<.05,Bonferroni(Dunn)t-test)hantheremainingthree PFOS exposurecategories. 2. Significantdliyfferen(tp< .05,Bonfeffoni(Dunn)t-testt)hanthe0 -< I ppm andthe I -< 3 ppm categories. 3. Significantdliyfferen(tp< .05,Bonferron(iDunn)t-testt)hanthe0 -< I ppm category. Table 8 MultivariablReegressionof Serum Chemistriesand HematologicalParameters-Examinationof the Effectof PFOS AdjustingforAge, Alcohol,BNE and Cigarettes, Antwerp and DecaturData Combined, 1995 and 1997 Examinations Intercept PFOS Age Alcohol BNE Cigarettes Parameter 52.99 0.32 0.08 -5.43 1.04 0.85 R 2 = .26 1995 Data SE 11.14 0.89 0.20 1.53 0.34 0.15 Adj R2 = .24 AlkalinePhosl2hatase ]2value .0001 .72 .68 .0005 .002 .0()Ol Parameter 40.87 0.19 0.45 -2.09 0.69 0.49 R 2 = .19 1997 Data SE ]2value 9.60 .0001 1.03 .86 0.18 .01 1.61 .20 0.34 .04 0.15 .002 Adj R 2 = .16- Intercept PFOS Age Alcohol BNE Cigarettes Parameter 2.3816 0.0032 0.0040 0.0605 0.0372 0.0076 R 2 = .14 1995 Data SE 0.2711 0.0217 0.0048 0.0373 0.0082 0.0038 Adj R 2 = .12 InGGT R value .0001 .88 .41 .11 .0001 .05 Parameter 2.0471 0.0178 0.0036 0.0747 0.0365 0.0030 R'=.15 1997 Data SE 0.2592 0.0280 0.0049 0.0438 0.0091 0.0042 Adj R2 =.12 12value .0001 .53 .47 .09 .0001 .48 Intercept PFOS Age Alcohol BNH Cigarettes Parameter 12.62 0.42 0.0005 0.70 0.54 -0.11 R 2 = .08 1995 Data SE 5.52 0.44 0.10 0.76 0.17 0.08 Adj R 2 = .05 AST R value .02 .35 .99 .36 .002 .14 Parameter 23.25 -0.11 -0.07 0.40 0.23 -0.07 R 2 =.04 1997 Data SE 3.50 0.38 0.07 0.59 0.12 0.06 Adj R 2 =.00 p value .0001 .77 .29 .50 .07 .20 Table8 (continued) Intercept PFOS Age Alcohol BMI Cigarettes Parameter 28.54 0.09 -0.18 -0.16 0.96 -0.14 R 2 = .08 1995 Data SE 9.46 0.76 0.17 1.30 0.29 0.13 Adj R 2 = .05 ALT 12value .003 91 .28 .90 .001 .28 Parameter 11.60 0.97 -0.19 0.31 1.00 -0.09 R2 =.13 1997 Data SE 6.78 0.73 0.13 1.14 0.24 0.11 Adj R 2 = .10 r)value .09 .19 .14 .79 .0001 .40 Intercept PFOS pFOS2 Age Alcohol BNH Cijzarettes Parameter 0.2742 -0.0984 0.0086 0.0052 0.0738 -0.0273 -0.0158 R 2 = .32 1995 Data SE 0.1958 0.0368 0.0039 0.0035 0.0268 0.0059 0.0028 Adj R 2 = .30 InTotalBilirubin p value .16 .008 .03 .14 .007 .0001 .0001 Parameter -0.1395 -0.1620 0.0188 0.0015 0.1220 -0.0097 -0.0054 R'=.18 1997 Data SE 0.1945 0.05-15 0.0070 0.0037 0.0327 0.0068 0.0031 Adj R 2 = .14 12value .47 .002 .009 .70 .0003 .16 .09 Intercept PFOS Age Alcohol BNU Cijzarettes Parameter 0.2196 -0.0009 0.0006 0.0074 -0.0012 -O.OW7 R 2 = .06 1995 Data SE 0.0259 0.0021 0.0005 0.0036 0.0008 0.0004 Adj R 2 .03 DirectBilirubin R value .0001 .68 .17 .04 .13 .06 Parameter 0.1929 -0.0061 -0.0002 0.0106 -0.0017 -O.OW9 R'=.14 1997 Data SE 0.0264 0.0029 0.0005 0.0045 0.0009 0.0004 Adj R 2 =.Il 12value .0001 .03 .69 .02 .07 .05 Table 8 (continued) Intercept PFOS Age Alcohol BNH Ci-garettes Parameter 18.64 -0.02 -0.03 0.37 -0.05 -0.08 R 2 = .08 1995 Data SE 1.94 0.15 0.03 0.27 0.06 .03Adj R 2 = .05 BUN R value .0001 .91 .39 .17 .42 .004 Parameter 13.22 -0.08 0.08 0.50 -0.07 -0.05 R 2 =.Og 1997 Data SE 1.47 0.16 0.03 0.25 0.05 0.02 Adj R 2 = .06 p value .0001 .60 .005 .05 .20 .05 Intercept PFOS PFOS' Age Alcohol BNE Cigarettes Parameter 0.5744 -0.0223 0.0033 0.0059 -0.0260 0.0086 -0.0005 R 2 = .29 1995 Data SE 0.0779 0.0146 0.0016 0.0013 0.0106 0.0023 0.0011 Adj R 2 = .27 Creatinine R value .0001 .13 .04 .0001 .02 .0003 .65 Parameter 0.9478 -0.0302 0.0055 0.0027 -0.0242 -0.0022 -0.0019 R'=.16 1997 Data SE 0.0602 0.0159 0.0022 0.0012 0.0101 0.0021 0.0010 Adj R 2 =.13 R value .0001 .06 .01 0.02 .02 .30 .05 Intercept PFOS Age Alcohol BNH Cigarettes Parameter 3.8943 -0.0039 0.0045 -0.0026 0.0143 -O.OW3 R 2 = .31 1995 Data SE 0.0732 0.0058 0.0013 0.0101 0.0022 0.0010 Adj R 2 = .29 In Glucose R value .0001 .51 .0006 .79 .0001 .78 Parameter 3.8597 0.0014 0.0025 -0.0068 0.0195 -0.0013 R 2 =.30 1997 Data SE 0.0919 0.0098 0.0017 0.0154 0.0032 0.0015 Adj R 2 .27 R value .0001 .89 .15 .66 .0001 .39 Intercept PFOS Age Alcohol BNU Cigarettes Parameter 190.1 -0.99 0.74 -0.40 -0.04 -0.18 R 2 = .02 Table8 (continued) 1995 Data SE 22.1 1.77 0.39 3.04 0.67 0.31 AdjR'=.00 Cholesterol R value .0001 .58 :06 .90 .95 .56 Parameter 155.5 4.66 1.39 7.50 -0.40 -0.08 R'=.17 1997 Data SE 19.0 2.04 0.36 3.18 0.67 0.30 Adj R 2 =.14 R value .0001 .02 .0002 .02 .55 .80 Intercept PFOS Age Alcohol BNE Cigarettes Parameter 135.26 0.50 0.58 -3.33 -6.67 -0.52 R 2 = .05 1995 Data SE 20.27 1.61 0.36 2.78 0.61 0.28 Adj R 2 = .02 LDL R value .0001 .76 .11 .23 .28 .07 Parameter 114.69 4.01 1.04 4.29 -1.09 -0.02 R 2 = .13 1997 Data SE 17.06 1.82 0.32 2.84 0.60 0.28 Adj R 2 = .10 p value .0001 .03 .002 .13 .07 .95 Intercept PFOS Age Alcohol BNH Ci%zarettes Parameter 70.82 -1.17 -0.11 3.53 -0.63 -0.17 R 2 = .28 1995 Data SE 5.73 0.46 0.10 0.79 0.17 0.08 Adj R 2 .26 HDL R value .0001 .01 .27 .0001 .0004 0.03 Parameter 66.71 -0.22 0.12 2.01 -0.95 -0.16 R 2 = .29 1997 Data SE R value 4.52 .0001 0.49 .65 0.09 .17 0.76 .009 0.16 .0001 0.07 .03 Adj R 2 .26 Intercept PFOS Age Alcohol BMI Cigarettes Parameter -103.29 -1.78 1.54 -0.43 6.71 2.70 R 2 = .24 Table8 (continued) 1995 Data SE 45.97 3.68 0.82 6.32 1.39 0.64 Adj R' = .22 Tri-glycerides 12value .03 .63 .06 95 .0001 .0001 Parameter -187.99 -0.33 1.37 14.68 10.06 1.87 R' = .23 1997 Data SE 58.18 6.28 1.11 9.82 2.05 0.94 Adj R 2 = .20 p value .002 .96 .22 .14 .0001 .05 Intercept PFOS Age Alcohol BMI Cigarettes Parameter 48.01 -0.06 0.0005 0.10 -0.08 0.05 R' = .08 1995 Data SE 1.36 0.11 0.02 0.19 0.04 0.02 Adj R 2 = .05 Hematocrit p value .0001 .57 .98 .58 .06 .007 Parameter 46.73 -0.25 -0.03 0.15 0.01 0.04 R 2 = .08 1997 Data SE 1.28 0.14 0.02 0.22 0.05 0.02 Adj R 2 = .04 D value .0001 .07 .20 0.50 0.75 .04 Intercept PFOS Age Alcohol BMI Cigarettes Parameter 15.78 -0.02 0.004 -0.02 -0.03 0.02 R 2 = .06 Hemoglobin 1995 Data 1997 Data SE p value Parameter SE R value 0.45 .0001 15.43 0.43 .0001 0.04 .53 -0.08 0.05 .07 0.008 .57 -0.006 0.01 .46 0.06 .77 0.01 0.07 .85 0.01 .06 0.008 0.02 .59 0.006 .02 Adj R 2 .03 0.02 R 2 = .06 0.007 .03 Adj R 2 .03 Intercept PFOS Age Alcohol BNU Cijzarettes Parameter 4.8766 -0.0026 -0.0022 -0.0323 0.0069 -0.0006 R 2 = .()4 Table 8 (continued) RBC 1995 Data SE 12value 0.1559 .0001 0.0123 .83 0.0028 .42 0.0213 :13 0.0047 .14 0.0022 .77 Adj R 2 .0.1 Parameter 5.1416 -0.0208 -0.0068 -0.0111 0.0089 -0.0025 R 2 = .06 1997 Data SE 0.1626 0.1756 0.0031 0.0274 0.0057 0.0026 Adj R' .02 p value .0001 .24 .03 .69 .12 .35 Intercept PFOS Age Alcohol BNU Cigarettes Parameter 32.292 -0.015 0.23 0.189 -0.093 0.0347 R 2 = .20 1995 Data SE 0.725 0.058 0.013 0.099 0.022 0.010 Adj R 2 = .18 MCH R value .0001 .79 .08 .06 .0001 .001 Parameter 30.062 -0.047 0.028 0.095 -0.035 0.046 R 2 = .13 1997 Data SE 0.706 0.076 0.013 0.119 0.025 0.011 Adj R 2 = .10 R value .0001 .54 .04 .43 .16 .0001 Intercept PFOS Age Alcohol BNE Cigarettes Parameter 32.8525 -0.0015 0.0097 -0.1121 -0.0006 -0.0041 R 2 = .07 1995 Data SE 0.3341 0.0266 0.0059 0.0458 0.0100 0.0047 Adj R 2 .05 MCHC p value .0001 .96 .11 .02 .95 .39 Parameter 33.0109 -0.0092 0.0101 -0.0589 0.0072 0.0016 R 2 .07 1997 Data SE 0.2675 0.0289 0.0051 0.0451 0.0094 0.0043 Adj R 2 =.04 p value .0001 .75 .05 .19 .45 .72 Intercept PFOS Age Alcohol BNH Cigarettes Parameter 98.29 -0.03 0.04 0.88 -0.28 0.12 R 2 = .23 Table8 (continued) 1995 Data SE 2.29 0.18 0.04 0.31 0.07 0.03 Adj R 2 = .21 mcv p value .0001 .88 .33 :01 .0001 .0005 Parameter 90.91 -0.09 0.06 0.49 -0.12 0.13 R 2 = .15 1997 Data SE 1.98 0.21 0.04 0.33 0.07 0.03 Adj R'=.12 r)value .0001 .67 .15 .14 .08 .0001 Intercept PFOS Age Alcohol BNH Cigarettes Parameter 272.49 -3.37 -0.88 -4.80 -0.04 0.21 R 2 =.06 1995 Data SE 23.37 1.86 0.41 3.20 0.70 0.33 Adj R 2 = .03 Platelets R value .0001 .07 .04 .14 .95 0.52 Parameter 260.92 -2.91 -0.25 2.37 -0.73 -0.30 R 2 = .03 1997 Data SE 25.27 2.73 0.48 4.26 0.89. 0.41 Adj R 2 = .00 R value .0001 .29 .61 .58 .41 .46 Intercept PFOS Age Alcohol BNH Cigarettes Parameter 3.9538 0.0893 0.0214 -0.0860 0.0492 0.1009 R 2 = .36 1995 Data SE 0.8120 0.0646 0.0144 0.1111 0.0244 0.0115 Adj R 2 = .34 WBC R value .0001 .17 .14 .44 .05 .()()Ol Parameter 5.1296 -0.0048 0.0139 0.2471 0.0045 0.0878 R 2 = .33 1997 Data SE 0.6927 0.0748 0.0132 0.1169 0.0244 0.0111 Adj R 2 = .31 p value .0001 .95 .30 .04 .86 .0001 Table 9 MultivariablReegressionofTotalBilirubinD,irectBilirubinC,reatininCeholesterolL,DL, HDL, Heamtocrit,Hemoglobin and Platelet-sExaminationof theEffectof PFOS AdjustingforAge, Alcohol,BNH and Cigarettesb,y Location,1995 and 1997 InTotalBilirubi-nBoth Locations Intercept PFOS pFOS2 Age Alcohol BM Cigarettes Parameter 0.2742 -0.0984 0.0086 0.0052 0.0738 -0.0273 -0.0158 R 2 = .32 1995 Data SE 0.1958 0.0368 0.0039 0.0035 0.0268 0.0059 0.0028 Adj R' = .30 p value .16 .008 .03 .14 .007 .0001 .0001 Parameter -0.1395 -0.1620 0.0188 0.0015 0.1220 -0.0097 -0.0054 R 2 = .18 1997 Data SE 0.1945 0.0515 0.0070 0.0037 0.0327 0.0068 0.0031 Adj R 2 = .14 p value .47 .002 .009 .70 .0003 .16 .09 InTotalBilirubin-AntweEp Onl-y Intercept PFOS pFOS2 Age Alcohol BNU Cijzarettes Parameter -0.0776 -0.0473 0.0035 0.0062 0.0398 -0.0115 -0.0176 R 2 = .15 1995 Data SE 0.0475 0.0575 0.0072 0.0055 0.0316 0.0161 0.0056 Adj R 2 = .08 R value .85 .41 .63 .27 .21 .48 .002 Parameter -0.3130 -0.2157 0.0336 -0.0036 0.0826 0.0114 -0.0102 R'=.14 1997 Data SE -Rvalue 0.5586 0.58 0.1779 .23 0.0385 .39 0.0081 .66 0.0441 .07 0.0222 .61 0.0074 .17 Adj R 2 = .05 InTotalBilirub-iDnecaturOply Intercept PFOS pFOS2 Age Alcohol BNH Cigarettes Parameter -0.4462 -0.0862 0.0081 0.0128 -0.0045 -0.0179 -0.0117 R 2 = .29 1995 Data SE 0.3154 0.0509 0.0048 0.0048 0.0828 0.0068 0.0031 Adj R 2 12value 16 .09 .10 .01 .59 .01 .0004 .24 1997 Data Parameter SE 12value -0.9486 0.2932 .002 -0.1160 0.0578 .05 0.0144 0.0072 .05 0.0134 0.0046 .005 0.1708 0.1607 .29 -0.0045 0.0073 .54 -0.0031 0.0032 .33 R 2 = .17 Adj R 2=.Io Table 9 (continued) HDL -Both Locations Intercept PFOS Age Alcohol BNH Cigarettes 1995 Parameter 70.82 -1.17 -0.11 3.53 -0.63 -0.17 R 2 = .28 Data (N SE 5.73 0.46 0.10 0.79 0.17 0.08 Adj R' = 178) R value .0001 .01 .27 .0001 .0004 0.03 .26 1997 Data (N 149) Parameter SE R value 66.71 4.52 .0001 -0.22 0.49 .65 0.12 0.09 .17 2.01 0.76 .009 -0.95 0.16 .0001 -0.16 R' = .28 0.07 .03 Adj R 2 = .26 HDL - Antwga Only Intercept PFOS Age Alcohol BNH Cigarettes 1995 Data (N = 86) Parameter SE R value 73.44 12.69 .0001 -1.55 0.73 .04 0.01 0.17 .93 3.31 0.98 .001 -0.87 0.50 .09 -0.19 R 2 = .16 0.17 .28 Adj R 2 = .11 1997 Data(N = 63) Parameter SE ' R value 57.30 12.12 .0001 -2.26 1.17 .06 0.43 0.17 .01 2.78 0.99 .007 -0.82 0.48 .10 -0.45 R 2 = .28 0.16 .007 Adj R 2 =.21 HDL -DecaturOnly Intercept PFOS Age Alcohol BNH Cigarettes 1995 Parameter 66.35 -0.75 -0.14 4.71 -0.49 -0.16 R 2= .14 Data (N = 85) SE 9.42 0.60 0.14 2.48 0.21 0.09 Adj R' = .09 12value .0001 .22 .32 .06 .02 .09 1997Data (N = 83) Parameter SE 12value 69.17 7.01 .0001 0.17 0.50 .73 0.01 0.11 .96 -3.07 3.87 .43 -0.90 0.18 .0001 -0.04 R 2 = .27 0.08 .61 Adj R 2 =.22 Intercept PFOS Age Alcohol Bl@U Cijzarettes Parameter 272.49 -3.37 -0.88 -4.80 -0.04 0.21 R 2 = .06 Table 9 (continued) Platelet-sBoth Locations 1995 Data SE 23.37 1.86 0.41 3.20 0.70 0.33 Adj R 2 = .03 p value .0001 .07 .04 .14 .95 .52 Parameter 260.92 -2.91 -0.25 2.57 -0.73 -0.30 R 2 = .03 1997 Data SE 25.27 2.73 0.48 4.26 0.89 0.41 Adj R 2 = .00 R value -.0001 .29 .61 .58 .41 .46 Intercept PFOS Age Alcohol BMI Cigarettes Parameter 294.81 -2.57 -0.35 -3.65 -2.23 0.82 R 2 =.06 PlateletAsn,tweIR Only 1995 Data SE 48.19 2.77 0.65 3.74 1.91 0.65 Adj R 2 =.Oo p valu .0001 .36 .60 .33 .25 .21 Parameter 258.21 -1.99 0.41 -0.87 -1.16 -0.70 R 2 =.02 1997 Data SE 66.58 6.44 0.91 5.42 2.65 0.90 Adj R 2 =.Oo p value .0003 .76 .65 .87 .66 .44 Intercept PFOS Age Alcohol BNU Cijzarettes Parameter 353.90 -6.08 -1.99 5.36 -0.64 -0.35 R'=.19 PlateletDse,caturOnly 1995 Data SE 39.04 2.50 0.59 10.14 0.84 0.40 Adj R 2 .14 I?value .0001 .02 .001 .60 .45 .38 Parameter 225.66 -2.75 -0.16 8.45 0.14 -0.19 R 2 = .01 1997 Data SE R value 42.96 .0001 3.09 .38 0.69 .82 23.70 .72 1.10 .90 0.47 .69 Adj R 2 = .()o Intercept PFOS PFOS 2 Age Alcohol BNE Cigarettes Parameter 0.5744 -0.0223 0.0033 0.0059 -0.0260 0.0086 -0.0005 R 2 = .29 Table 9 (continued) Creatinine- Both Locations 1995 Data SE 0.0779 0.0146 0.0016 0.0013 0.0106 0.0023 0.0011 Adj R2 = .27 p value .0001 13 .04 .0001 .02 .0003 .65 Parameter 0.9478 -0.0302 0.0055 0.0027 -0.0242 -0.0022 -0.0019 R 2 = .16 1997 Data SE 0.0602 0.0159 0.0022 0.0012 0.0101 0.0021 0.0010 Adj R 2 =.13 p value .0001 .06 .01 0.02 .02 .30 .05 Intercept PFOS pFOS2 Age Alcohol BNE Cigarettes Parameter 0.7319 -0.0324 0.0008 0.0044 -0.0055 0.0037 0.0017 R 2 = .20 Creatinine-AntweM Onl 1995 Data SE 0.1382 0.0195 0.0024 0.0019 0.0107 0.0055 0.0019 Adj R 2 = .14 12value .0001 .10 .74 .02 .61 .50 .36 Parameter 0.8600 -0.0453 0.0074 0.0033 -0.0142 -0.0012 0.0041 R 2 = .14 1997 Data SE 0.1430 0.0455 0.0099 0.0021 0.0113 0.0057 0.0019 Adj R 2 = .05 R value .0001 .32 .46 .11 .21 .83 .04 Intercept PFOS PFOS' Age Alcohol BNU Cigarettes .003 Parameter 0.8641 -0.0093 0.0036 0.0032 0.0082 0.0032 -0.0030 R 2 = .23 Creatinine- Decatur On] 1995 Data SE 0.1300 0.0206 0.0019 0.0020 0.0336 0.0028 0.0013 ]2value .0001 .65 .07 .11 .81 .26 .02 Adj R 2 .18 Parameter 1.1363 -0.0430 0.0067 0.0006 -0.1133 -0.0038 -0.0034 1997 Data SE 12value 0.1021 .0001 0.0201 .04 0.0025 .009 0.0016 .72 0.0559 .05 0.0026 .14 0.0011 R 2 = .27 Adj R 2 =.22 Intercept PFOS Age Alcohol BNH Cigarettes Parameter 190.1 -0.99 0.74 -0.40 -0.04 -0.18 R 2 = .02 Table 9 (continued) Cholesterol-Both Locations 1995 Data SE 22.1 1.77 0.39 3.04 0.67 0.31 AdjR'=.00 p value .0001 .@8 .06 .90 .95 .56 Parameter 155.5 4.66 1.39 7.50 -0.40 -0.08 R 2 =.17 1997 Data SE 19.0 2.04 0.36 3.18 0.67 0.30 Adj R 2 = .14 R value .0001 .02 .0002 .02 .55 .80 Intercept PFOS Age Alcohol BNE Cigarettes Parameter 62.17 -1.22 2.60 1.13 2.28 0.81 R 2 = .25 Cholestero-lAntwerp On] 1995 Data SE 43.72 2.51 0.59 3.39 1.73 0.59 Adj R' = .20 R value .16 .63 .0001 .74 .19 .17 Parameter 93.11 2.37 2.54 7.49 0.78 -0.23 R 2 = .33 1997 Data SE 49.20 4.74 0.67 3.98 1.95 0.66 Adj R 2 = .27 p value .06 .62 .0004 .06 .69 .72 Intercept PFOS Age Alcohol BNU Cigarettes Parameter 304.27 -1.03 -1.05 -21.16 -1.03 -0.40 R 2 = .14 Cholesterol-DecaturOnl 1995 Data SE 33.14 2.19 0.51 8.88 .73 0.33 Adj R 2 =.09 R value .0001 .64 .04 .02 .17 .23 1997 Data Parameter SE 207.01 31.55 4.26 2.27 0.48 0.51 19.54 17.41 -.78 0.81 -0.11 R 2 = .07 .35 Adj R 2 .01 R value .0001 .06 .35 .27 .34 .75 Intercept PFOS Age Alcohol BNH Cigarettes Parameter 135.26 0.50 0.58 -3.33 -6.67 -0.52 R 2 = .05 Table 9 (continued) 1995 Data SE 20.27 1.61 0.36 2.78 0.61 0.28 AdjR 2 = .02 LDL 13value .0001 .76 .11 .23 .28 .07 Parameter 114.69 4.01 1.04 4.29 -1.09 -0.02 R 2 = .13 1997 Data SE 17.06 1.82 0.32 2.84 0.60 0.28 Adj R 2 = .10 R value .0001 .03 .002 .13 .07 .95 LDL -AntweEp On] Intercept PFOS Age Alcohol BNH Cigarettes Parameter 12.14 0.24 2.15 -3.04 2.04 0.35 R' = .20 1995 Data -SE 41.44 2.38 0.56 3.21 1.64 0.56 Adj R 2 = .15 R value .77 .92 .0003 .35 .22 .53 Parameter 40.88 1.50 2.22 4.12 0.48 0.26 R 2 = .29 1997 Data SE 42.42 4.08 0.58 3.43 1.68 0.57 Adj R 2 = .23 R value .34 .71 .0003 .23 .78 .65 LDL -DecaturOnly Intercept PFOS Age Alcohol BMI Cigarettes Parameter 218.24 1.06 -0.79 -22.95 -1.38 -0.65 R' = .20 1995 Data -SE - 30.58 1.96 0.46 8.04 0.67 0.30 Adj R 2 .15 D value .0001 .59 .09 .006 .04 .03 Parameter 160.50 3.55 0.20 -12.68 -1.27 -0.13 R 2 =.07 1997 Data SE 28.17 2.03 0.45 28.72 0.72 0.31 Adj R'=.Ol R value .0001 .08 .65 .66 .08 .67 Intercept PFOS Age Alcohol B@M Cijzarettes Parameter 48.01 -0.06 0.0005 0.10 -0.08 0.05 R 2 = .08 Table 9 (continued) Hematociit-Both Locations 1995 Data 1997 Data SE p value Parameter SE i)value 1.36 .0001 46.73 1.28 .0001 0.11 57 -0.25 0.14 .07 0.02 .98 -0.03 0.02 .20 0.19 .58 0.15 0.22 0.50 0.04 .06 0.01 0.05 0.75 0.02 .007 Adj R 2 = .05 0.04 R 2 = .08 0.02 .04 Adj R 2 .04 Intercept PFOS Age Alcohol BNH Cigarettes Parameter 44.00 0.06 0.06 -0.12 0.02 0.05 R 2 = .08 Hematocrit-AntweEp Onl 1995 Data SE 2.30 0.13 0.03 0.18 0.09 0.03 Adj R 2 = .03 p value .0001 .63 .06 .51 .80 .14 Parameter 45.63 -0.29 0.04 0.06 -0.02 0.01 R 2 = .01 1997 Data SE 3.63 0.35 0.50 0.30 0.14 0.05 Adj R 2 = .00 p value .0001 .42 .37 .84 .89 .79 Intercept PFOS Age Alcohol BNU Cigarettes Parameter 45.56 -0.05 0.01 -0.56 -0.02 0.08 R 2 10 Hematocrit-DecaturOn] 1995 Data SE 2.62 0.17 0.04 0.68 0.06 0.03 Adj R 2 =.04 p value .0001 .79 .89 .41 .71 .004 Parameter 45.69 -0.28 -0.05 -1.52 0.08 0.06 R 2 = .19 1997 Data SE 1.95 0.14 0.03 1.08 0.05 0.02 Adj R 2 =.13 p value .0001 .05 .09 .16 .11 .006 Table 9 (continued) Hemo-globin- Both Locations Intercept PFOS Age Alcohol BNE Cigarettes Parameter 15.78 -0.02 0.004 -0.02 -0.03 0.02 R 2 = .06 1995 Data SE 0.45 0.04 0.008 0.06 0.01 0.006 Adj R 2 = .03 R value .0001 .53 .57 .77 .06 .02 Parameter 15.43 -0.08 -0.006 0.01 0.008 0.02 R 2 = .06 1997 Data SE 0.43 0.05 0.01 0.07 0.02 0.007 Adj R 2 = .03 12value .0001 .07 .46 .85 .59 .03 Intercept PFOS Age Alcohol BNII Cigarettes Parameter 14.72 0.008 0.02 -0.04 -0.007 0.005 R 2 = .08 Hemoglobin -AntweIR Only 1995 Data SE 0.74 0.04 0.01 0.06 0.03 0.01 Adj R 2 = .02 R value .0001 .86 .02 .51 .81 .61 Parameter 15.32 -0.10 0.02 0.02 -0.01 -0.006 R' = .03 1997 Data SE 1.15' 0.11 0.02 0.09 0.05 0.02 Adj R 2 =.00 12value .0001 .40 .33 .81 .81 .70 Intercept PFOS Age Alcohol BNH Cigarettes Parameter 15.87 -0.03 -0.004 -0.22 -0.02 0.02 R 2 = .10 Hemoglobin -DecaturOn] 1995 Data SE 0.90 0.06 0.01 0.23 0.02 0.009 Adj R 2 .04 12value .0001 .63 .79 .35 .32 .01 Parameter 15.58 -0.10 -0.02 -0.47 0.02 0.02 R 2 = .17 1997 Data SE 0.71 0.05 0.01 0.39 0.02 0.008 Adj R 2 =.12 12value .0001 .07 .12 .23 .25 .004 Table 9 (continued) Intercept PFOS Age Alcohol BNE Cigarettes Parameter 0.2196 -0.0009 0.0006 0.0074 -0.0012 -0.0007 R 2 =.06 Dir-ecBtilirubin-Both Locations 1995 Data SE 0.0259 0.0021 0.0005 0.0036 0.0008 0.0004 Adj R 2 = .03 1 p value .0001 .68 .17 .04 .13 .06 Paramcter 0.1929 -0.0061 -0.0002 0.0106 -0.0017 -0.0009 R 2 = .14 1997 Data SE 0.0264 0.0029 0.0005 0.0045 0.0009 0.0004 Adj R 2 = .11 p value ..Oool .03 .69 .02 .07 .05 Intercept PFOS Age Alcohol BNO Cijzarettes Parameter 0.1794 -0.0034 0.00004 0.0102 0.0017 -0.0016 R'=.17 DirectBilinibi-nAntweER Only 1995 Data SE 0.0461 0.0026 0.0006 0.0036 0.0018 0.00()() Adj R 2= .12 R value .0002 .21 .95 .006 .36 0.()()9 Parameter 0.1963 -0.0077 -0.0017 0.0112 0.0006 -0.0017 R 2= .14 1997 Data SE 0.0813 0.0079 0.0011 0.0066 0.0032 0.0011 Adj R 2 = .06 R value .02 .33 .13 .10 .84 .12 Intercept PFOS Age Alcohol BNE Ci-garettes Parameter 0.1972 0.0025 0.0012 -0.0114 -0.0016 -0.0001 R 2 = .07 DirectBilirubi-nDecaturOnly 1995 Data SE 0.0478 0.0032 0.0007 0.0128 0.0011 0.0005 Adj R 2 = .02 R value .0001 .44 0.11, .37 .13 .79 Parameter 0.1205 -0.0038 0.0014 -0.0042 -0.0018 -0.0004 R 2 =.15 1997 Data SE 0.0347 0.0025 0.0006 0.0191 0.0009 0.0004 Adj R 2 = .10 R value .0008 .13 .02 .83 .04 .27 Table 10 Summaries of Simple Linearand QuadraticRegressionModels forTotaland UnconjugatedBilirubin1,9 1995 Data 1997 Data TotalBilirubin Linear Ouadratic Both Locations Uncontugated Linear Ouadratic TotalBilirubin Lineir Ouadratic Unc Linear - R2 .002 .052 intercept 0.78247 0.86532 PFOS(P value) -0.02927(.047) -0.00918(.03) PFOS2 (p value) 0.00846(.02) .024 0.56837 -0.0285(.04) .059 .016 0.65239 0.8175 -0.09941(.002) -0.02583(.12) 0.00858(.01) .046 0.78963 -0.10456(.01) 0.01200 (.03Y .012 0.57745 -0.01940 Antwe[p R2 .018 intercept 0.92001 PFOS (pvalue)-0.02927(.21) PFOS2 (pvalue) .028 0.96548 -0.07872(.18) 0.00697(.31) .017 0.69447 -0.02604(.23) .028 0.73919 -0.07468(.17) 0.00686(.32) .014 0.85170 -0.03647(.35) .052 0.96350 -0.22847(.08) 0.04620(.20) .012 0.69161 -0.02872 Decatur R2 .004 .010 Intercept 0.59712 0.66974 PFOS (pvalue)-0.014363(.53) -0.05867(.09) PFOS2 (p value) 0.00518(.12) .008 0.39803 -0.01166(.39) .029 0.48279 -0.06966(.03) 0.00605(.05) 0.009 0.59609 -0.00894(.53) .071 .002 0.68287 0.47268 -0.09408(.02) -0.00489 0.001143(.02) Table II Mean Values ofPFOS, Demographic, Serum Chemistry and Hematologic ParametersforAntwerp and Decatur Combined Locations,1995 and 1997 Examinations forEmployees Who Participateadnd Did Not ParticipatienBoth Years Variable PFOS (ppm) 1995 Data Both Years Only 1995 (N = 61) (N = 117) 2.40 2.08 1997 Data Both Years Only 1997 (N = 61) --- (N = 88) 2.34*** 1.34 Age 39* 42 41* 38 BNE 27.1 26.3 27.3 26.9 Cigarettes 5.4 6.7 5.2 6.8 Alcohol 0.8 0.6 0.4* 0.4 Alk Phosphatase 87 86 79 80 GGT 44 44 37* 27 AST 29 27 26 26 ALT 46 46 33 32 Totalbilirubin 0.71 0.72 0.65 0.69 Directbilirubin 0.21 0.22 0.13 0.13 BLJN 16.2 15.7 14.6 14.3 Creatinine 1.0 1.0 1.0 1.0 Glucose 86 87 93 89 Cholesterol 212 213 225*** 201 LDL 142 134 145*** 128 HDL 50 47 46 45 Table II (continued) Vaiiable 1995 Data Antwerp Decatur 1997 Data Antwerp Decatur Triglycerides 139 157 167 149 Hematocrit 45 47 46 46 Hemoglobin 15.0 15.5 15.3 15.4 RBC 4.9 5.0 5.0* 5.1 MCH 30.8 31.2 30.8* 30.2 MCHC 33.2 33.1 33.6 33.6 mvc 93 94 92** 90 WBC 6.6 7.0 6.5 6.4 Platelets 226 227 228 224 p <.05; p <.Ol; ***p<.ooi Table 12 Mean Values of PFOS, Demographic,Serum Chemistryand Hematologic Parameters forAntwerp and Decatur,1995 Examinations forEmployees Who Participateadnd Did notParticipatien Both 1995 and 1997 Variable PFOS(ppm) AntweER Both Years Pnly 1995 N = 27) (N = 61) 2.30 1.76 Decatur Both Years Only 1995 (N = 34) (N = 56) 2.48 2.42 Age 34 37 42* 46 BNH 24.0 23.9 29.6 29.0 Cigarettes 5.4 4.3 5.4 9.4 Alcohol 1.7* 1.0 0.1 0.2 Alk Phosphatase 75 75 96 98 GGT 46 39 43 50 AST 28 25 30 29 ALT 43 45 48 47 Totalbilirubin 0.91 0.84 0.54 0.59 Directbilirubin 0.23 0.22 0.19 0.21 BLTN 17.7 16.7 15.0 15.0 Creatinine 0.9 0.9 1.1 1.1 Glucose 78* 83 92 92 Cholesterol 209 216 232** 209 LDL 133 140 150** 128 HDL 56 53 46 42 Table 12 (continued) Variable 1995 Data Antwert) Decatur 1997 Data Antwerp Decatur Triglycerides 100 122 170 197 Hematocrit 46 47 44** 46 Hemoglobin 15.3 15.5 14.8** 15.4 RBC 4.9 4.9 4.9* 5.0 MCH 31.2 31.5 30.5 30.8 MCHC 33.0 32.8 33.4 33.4 mvc 95 96 91' 92 WBC 6.4 6.3 6.8* 7.8 Platelets 222 225 23.0 228 p <.05; p <.Ol; ***p <.001 Table 13 Mean Values of PFOS, Demographic, Serum Chemistryand Hematologic Parameters forAntwerp and Decatur,1997 Examinations forEmployees Who Participateadnd Did not ParticipatienBoth Years Variable PFOS(ppm) Age BNU Antweri) Both Years Only 1997 (N = 27) (N = 38) 2.33*** 0.88 37*** 30 24.4* 22.8 Decatur Both Years Only 1997 (N = 34) (N = 50) 2.35 1.69 45 44 29.5 29.9 Cigarettes 5.9 5.2 Alcohol 1.0 0.7 Alk Phosphatase 72 69 GGT 33* 21 AST 27 26 ALT 32 30 Totalbilirubin 0.77 0.81 4.7 7.9 0.1 0.2 85 88 41 32 26 26 34 34 0.56 0.59 Directbilirubin 0.14 0.16 BUN 15.2 14.6 Creatinine 0.9 0.9 Glucose 80 81 0.12 0.11 14.1 14.0 1.0 1.0 103 95 Cholesterol 224*** 192 226* 208 IDL 148 123 143 132 HDL 51 49 43 42 Table 13 (continued) Variable 1995 Data AntwerR Decatur 1997 Data AntweIR Decatur Tiiglycerides .125 101 201 185 Hematocrit 46 46 45 46 Hemoglobin 15.5 15.4 15.2 15.4 RBC 5.0 5.1 4.9** 5.1 MCH 30.8 30.4 30.9 30.0 MCHC 33.4 33.3 33.7 33.8 mvc 92 91 91* 89 WBC 6.8 6.3 6.4 6.5 Platelets 241 234 218 217 *p<.05; **p<.Ol; ***p<.001 Table 14 MultivariablReegressionof Serum Chemistriesand HematologicalParameters-Examinationof the Effectof PFOS AdjustingforAge, Alcohol,BNH and Cigarettes, Antwerp and DecaturEmployees (N = 61)Who ParticipateidnBoth the 1995 and 1997 Examinations Intercept PFOS Age Alcohol Bl@U Cigarettes Parameter .55.23 -1.71 0.42 -5.34 0.70 0.82 R 2 = .24 1995 Data SE 22.22 1.77 0.43 2.47 0.67 0.34 Adj R 2 = .17 AlkalinePhosl2atase R value .02 .34 .33 .04 .30 .02 Parameter 45.74 0.46 0.33 -2.93 0.62 0.76 R 2 =.15 1997 Data SE 22.07 1.71 0.37 2.36 0.61 0.32 Adj R 2 = .07 12value .04 .79 .37 .22 .31 .02 Intercept PFOS Age Alcohol BNE Cigarettes Parameter 2.5359 -0.0028 -0.0078 0.0795 0.0469 0.0023 R 2 .14 1995 Data SE 0.5561 0.0443 0.0107 0.0619 0.0167 0.0084 Adj R 2 = .06 InGGT p value .0001 .95 .47 .20 .007 .79 Parameter 2.5660 -0.0357 -0.0095 0.0673 0.0463 -0.0025 R 2 = .14 1997 Data SE 0.5965 0.0461 0.0010 0.0638 0.0165 0.0087 Adj R 2 = .07 R value .0001 .44 .35 .30 .007 .77 Intercept PFOS Age Alcohol BNU Cigarettes Parameter 15.27 0.40 0.17 1.01 0.24 -0.26 R 2 = .08 1995 Data SE 11.19 0.89 0.22 1.25 0.34 0.17 Adj R 2 SGOT p value .18 .65 .42 .42 .47 .13 Parameter 21.68 -0.22 0.001 0.47 0.17 0.07 R 2 = .03 1997 Data SE 6.80 0.53 0.11 .73 0.19 0.10 Adj R 2 R value .002 .67 .99 52 .38 .49 Intercept PFOS Age Alcohol BNU Cigarettes Parameter 26.32 -0.03 -0.20 0.13 1.05 -0.25 R 2 = .10 Table 14 (continued) 1995 Data SE 17.83 1.42 0.34 1.98 0.54 0.27 Adj R 2 = .02 SGPT p value 115 .98 .57 .95 .06 .35 Parameter 15.34 0.27 -0.34 0.22 1.15 -0.04 R 2 = .18 1997 Data SE 13.86 1.07 0.23 1.48 0.38 0.20 Adj R 2= .11 R value .27 .80 .14 .88 .004 .83 Intercept PFOS pFOS2 Age Alcohol BNU Ci.garettes Parameter 0.7086 -0.0874 0.0081 -0.0030 0.0344 -0.0319 -0.0130 R 2 = .23 1995 Data SE 0.3971 0.0806 0.0068 0.0073 0.0436 0.0115 0.0060 Adj R 2 = .14 InTotalBilirubin R value Parameter .08 -0.3739 .28 0.0202 .24 -0.0014 .69 0.0072 .43 0.1045 .01 - -0.0182 .03 -0.0105 R 2 =.Ig 1997 Data SE 0.3996 0.0308 0.0026 0.0068 0.0426 0.0112 0.0058 Adj R 2 =.10 R value .35 .51 .58 .29 .02 .11 .08 Intercept PFOS Age Alcohol BNU Cigarettes Parameter 0.2579 -0.0027 -0.0019 0.0049 0.0010 -0.0005 R 2 = .13 1995 Data SE 0.0469 0.0037 0.0009 0.0052 0.0014 0.0007 Adj R 2 .05 DirectBilirubin R value .0001 .47 .04 .35 .49 .50 Parameter 0.1711 -0.0026 0.0004 0.0089 -0.0021 -0.0008 R 2 =.14 1997 Data SE 12value 0.0462 .0005 0.0036 .47 0.0008 .60 0.0049 .08 0.0013 .10 0.0007 .22 Adj R 2 =.07 Table 14 (continued) Intercept PFOS Age Alcohol BNE Cijzarettes Parameter 18.33 -0.09 -0.01 0.59 -0.04 -0.15 R 2 = .16 1995 Data SE 3.62 0.29 0.07 0.40 0.11 0.05 Adj R 2 =.Og BUN p value .0001 .75 .87 .15 .71 .007 Parameter 14.06 0.29 0.07 0.18 -0.12 -0.03 R 2 = .08 1997 Data SE 3.09 0.24 0.05 0.33 0.09 0.04 Adj R 2 =.00 12value .0001 .22 .16 .59 .18 .55 Intercept PFOS pFOS2 Age Alcohol BNU Ci-garettes Parameter 0.5185 -0.0515 0.0068 0.0073 -0.0100 0.0099 -0.0003 R 2 = .49 1995 Data SE 0.1308 0.0264 0.0022 0.0024 0.0143 0.0038 0.0019 Adj R 2 = .43 Creatinine 12value .0002 .06 .004 .004 .49 .01 .89 Parameter 0.8785 0.0168 -0.0005 0.0036 -0.0266 -0.0030 -0.0028 R 2 = .18 1997 Data SE 0.1333 0.0103 0.0009 0.0023 0.0142 0.0037 0.0020 Adj R 2 .09 R value .0001 .11 .57 .12 .07 .43 .15 Intercept PFOS Age Alcohol BNE Cigarettes Parameter 3.7479 -0.0017 0.0008 -0.0050 0.0236 0.0023 R 2 = .46 1995 Data SE 0.1311 0.0103 0.0025 0.0145 0.0039 0.0020 Adj R 2 .41 InGlucose R value .0001 .87 .74 .73 .0001 .26 Parameter 3.4111 0.0036 0.0063 0.0005 0.0306 -0.0051 R 2 .48 1997 Data SE 0.2013 0.0156 0.0034 0.0215 0.0056 0.0029 Adj R 2 .43 p value .0001 .82 .07 .98 .0001 .09 Intercept PFOS Age Alcohol BNE Cigarettes Parameter 184.37 -1.15 1.37 -2.72 -0.24 -0.82 R 2 =.13 Table 14 (continued) 1995 Data SE 34.59 2.76 0.67 3.85 1.04 0.52 AdjR 2 .05 Cholesterol p value .0001 p8 .04 .48 .81 .12 Parameter 179.50 3.75 0.73 6.57 0.09 -0.07 R 2 =.09 1997 Data SE 38.87 3.01 0.65 4.16 1.07 0.57 Adj R'=.Ol p value .0001 .22 .27 .12 .94 .90 Intercept PFOS Age Alcohol BNE Cigarettes Parameter 115.89 0.36 1.26 -3.74 -0.61 -0.72 R 2 = .15 1995 Data SE 30.35 2.38 0.58 3.35 0.91 0.45 AdjR 2 .07 LDL p value .0004 .88 .88 .27 .51 .12 Parameter 150.88 2.68 0.44 3.81 -1.20 -0.10 R 2 = .07 1997 Data SE 34.90 2.70 0.58 3.73 0.96 0.51 Adj R 2 = .00 p value .0001 .33 .45 .31 .22 .85 Intercept PFOS Age Alcohol BNU Cigarettes Parameter 75.25 -0.68 -0.0005 2.31 -0.86 -0.30 R 2 = .25 1995 Data SE 11.01 0.86 0.21 1.21 0.33 0.17 Adj R 2 = .18 HDL p value .0001 .44 .99 .06 .01 .08 Parameter 68.22 -0.33 0.11 2.10 -0.97 -0.12 R 2 = .34 1997 Data SE 8.91 0.69 0.15 0.95 0.25 0.13 Adj R 2 = .28 p value .0001 .63 .47 .03 .0002 .37 Intercept PFOS Age Alcohol BMI Cigarettes Parameter -89.52 -3.78 0.72 -1.93 7.50 1.40 R 2 = .26 Table 14 (continued) 1995 Data SE 66.79 5.32 1.29 7.43 2.00 1.01 Adj R 2= .19 Triglycerides p value .19 .48 .58 .80 .0004 .17 Parameter -198.05 7.03 0.87 3.28 11.26 0.73 R' =.38 1997 Data SE 82.02 6.35 1.37 8.77 2.26 1.19 Adj R 2 = .32 ]2value .02 .27 .53 .71 .0001 .54 Intercept PFOS Age Alcohol Bi@u Cigarettes Parameter 50.87 -0.03 -0.05 0.09 -0.13 0.05 R 2 = .20 1995 Data -SE - 2.15 0.17 0.04 0.24 0.06 0.04 Adj R 2 = .13 Hematocrit i)value .0001 .87 .19 .70 .04 .21 Parameter 46.61 -0.20 -0.04 0.31 0.02 0.06 R'=.10 1997 Data SE 2.56 0.20 0.04 0.270.07 0.04 Adj R 2 = .02 p value .0001 .33 .38 .26 .77 .14 Intercept PFOS Age Alcohol BNU Cigarettes 1995 Data Parameter SE 17.09 ...... 0.72 -0.02 0.06 -0.01 0.01 -0.002 0.08 -0.06 0.02 0.003 R 2 = .18 0.01 Adj R 2= .10 Hemoglobin 1997 Data R value Parameter SE .0001 15.55 0.88 .70 -0.07 0.07 .36 -0.01 0.01 .98 0.05 '0.09 .01 0.01 0.02 .79 0.02 0.01 R 2 .07 Adj R 2 .00 R value .0001 .33 .44 .61 .70 .12 Intercept PFOS Age Alcohol BNH Cigarettes Parameter 5.21 0.002 -0.003 -0.006 -0.007 -0.005 R 2 = .06 Table 14 (continued) 1995 Data SE 0.22 0.018 0.004 0.025 0.007 0.004 Adj R 2 = .03 RBC 12value .0001 89 .55 .81 .28 .18 Parameter 5.02 -0.003 -0.003 0.025 0.004 -0.005 R 2 = .04 1997 Data SE 0.30 0.024 0.005 0.033 0.008 0.004 Adj R 2 =.04 R value .0001 .88 .53 .44 .64 .28 Intercept PFOS Age Alcohol BMI Cigarettes Parameter 32.97 -0.05 -0.01 0.04 -0.07 0.04 R 2 = .18 1995 Data SE 1.25 0.10 0.02 0.14 0.04 0.02 Adj R 2 = .10 MCH 12value .0001 .60 .67 .79 .07 .06 Parameter 31.13 -0.11 -0.004 -0.06 -0.007 0.07 R 2 = .19 1997 Data SE 1.43 0.11 0.024 0.15 0.039 0.02 Adj R 2 =.12 12value .0001 .31 .85 .71 .86 .001 Intercept PFOS Age Alcohol BNE Cigarettes Parameter 33.55 -0.03 0.01 -0.08 -0.02 -0.02 R 2 = .18 1995 Data SE 0.53 0.04 0.01 0.06 0.02 0.01 Adj R 2 = .10 MCHC 12value .0001 .55 .20 .18 .17 .01 Parameter 33.40 -0.005 0.005 -0.10 0.001 0.003 R 2 =.09 1997 Data SE 0.50 0.039 0.008 0.05 0.014 0.007 Adj R 2 = .01 R value .0001 .89 .55 .07 .92 .69 Intercept PFOS Age Alcohol BMI Cigarettes Parameter 98.33 -0.09 -0.07 0.30 -0.15 0.19 R' = .27 Table 14 (continued) 1995 Data SE 3.59 0.29 0.07 0.40 0.11 0.06 Adj R' = .20 mcv p value .0001 76 .34 .45 .18 .003 Parameter 92.85 -0.28 -0.02 0.19 -0.03 0.20 R 2 =.22 1997 Data SE 3.82 0.30 0.06 0.41 0.11 0.06 Adj R 2 =.15 p value .0001 .34 .76 .65 .78 .0008 Intercept PFOS Age Alcohol BNU Cigarettes Parameter 295.55 -3.96 -0.84 -10.54 -0.54 -0.78 R 2= .19 1995 Data SE 37.09 2.96 0.71 4.13 1.12 0.63 Adj R 2 = .11 Platelets R value .0001 .19 .24 .01 .63 .22 Parameter 392.12 -3.84 -2.31 -6.59 -1.85 -0.82 R 2 = .21 1997 Data SE 48.22 3.73 0.81 5.16 1.33 0.70 Adj R 2 = .14 i)value .0001 .31 .006 .21 .17 .25 Intercept PFOS Age Alcohol BNE Cigarettes Parameter 3.10 0.03 0.002 0.07 0.10 0.12 R 2 = .43 1995 Data SE 1.19 0.09 0.023 0.13 0.04 0.02 Adj R 2 .38 WBC R value .01 .77 .93 .62 .007 .()()Ol Parameter 4.46 -0.04 -0.007 0.21 0.06 0.11 R 2 = .40 1997 Data SE 1.36 0.11 0.02 0.15 0.04 0.02 Adj R 2 .34 R value .002 .70 .75 .15 .09 woi PFOS (R]2m) 0 -< 1 I-< 3 3-<6 >= 6 Table 15 Employee Distributioans toPlantLocationand Whether Hormones Were Measured,1995 Total 45 91 35 7 178 Both Locations Hormones Yes 10(22%) 46(51%) 27(77%) 5(71%) 88 Measured No j5 (78%) 45(49%) 8(23%) 2(29%) 90 By Location Antwerp Decatur Hormones Measured Hormones Me Yes No Yes 9(27%) 25(73%) 1(9%) 21(66%) 11(34%) 25(43%) -18(95%) 1(5%) 9(56%) 2(670/o) 1(33%) 3(75%) 50 38 38 Table 16 Mean Values forPFOS, Demographic,Serum Chemistriesand Hematology, by PlantLocationand Whether Hormones Were Measured, 1995 Variable Both Locations Hormones Measured Yes No N = 88 N = 90 PFOS 2.87 1.52 Age Alcohol 38.4 42.7 ** 1.0 0.4 BMI 26.5 26.7 Cigarettes 8.3* 4.3 BUN 16.3 15.5 Creatinine 0.97* 1.02 Glucose 86 88 AlkalinePhosphatase86 86 Antwerp Hormones Measured Yes No N=50 N=38 2.69*** 0.92 35.0* 38.4 1.6** 0.8 23.6 24.4 ** 6.7 1.9 17.1 16.8 0.87 0.94 80 84 77 73 Decatur Hormones Measured Yes No N=38 N=52 3.10** 1.96 42.9 45.9 0.2 0.2 30.3 28.5 10.3 6.o 15.1 14.5 1.10 1.08 94 90 99 96 Variable GGT AST ALT TotalBilirubin DirectBilirubin Cholesterol LDL HDL Triglycerides Hematocfit Hemoglobin Both Locations Hormones Measured Yes No N=88 N=90 47 42 29 27 47 45 0.7 0.8 0.2 0.2 217 215 136 137 49 48 158 144 47 46 15.4 15.3 Table 16 (continued) Antwelp Hormones Measured Yes No N=50 N=38 45 37 27 24 44 45 0.8 0.9 0.2 0.2 210 220 133 144 52 55 124 104 47 47 15.4 15.4 Decatur Hormones Measured Yes No N=38 N=52 50 46 31 29 51 45 0.5 0.6 0.2 0.2 227 211 141 132 43 43 205 174 46 45 15.3 15.1 Vaiiable Both Locations Hormones Measured Yes No N=88 N = 90 RBC 5.0 4.9 MCH 31.1 31.0 MCHC 33.0* 33.3 mcv 94 93 WBC 7.3 6.5 Platelets 230 223 p <.05; p <.01;***p <.Ool Table 16 (continued) AntweM Hormones Measured Yes No N=50 N=38 4.9 4.9 31.5 31.3 32.9 32.8 96 95 6.8 5.7 233** 212 Decatur Hon-nones Measured Yes No N=38 N=52 5.0 4.9 30.5 30.8 33.2* 33.5 92 92 8.0* 7.0 226 231 Table 17 Mean, Median (N4ed),StandardDeviation(SD) ofMean and Range ofPFOS, Demographic, Serum Chemistriesand HematologicalValues forN = 88 Employees,Antwerp and DecaturCombined, who Had Hormone Measurements, 1995 PFOS (P-MP) Mean Med SD Range 0 -< 1 1-< 3 3-<6 >6 PFOS 0.68' 0.75 0.21 0.37-0.90 1.96' 1.96 0.62 1.00-2.90 4.15' 3.97 0.85 3.00-5.80 8.67' 8.50 2.85 6.06-12.83 F value= 121.3,p =.0001 0 -< 1 1-< 3 3 -< 6 >6 - Age 32.7 32.5 6.3 38.7 39.0 8.4 39.0 39.0 7.6 43.0 42.0 7.8 F value= 2.4,p =.08 21.0-43.0 25.0-58.0 26.0-54.0 37.0-56.0 0 -< 1 1-< 3 3 -< 6 >6 Alcohol 1.4 1.1 1.2 0.0-3.6 0.6 0.2 0.8 0.0-3.6 1.4 0.5 2.0 Olp-6.0 0.9 0.0 1.3 0.0-2.9 F value= 2.1, p=.Il 0 -< 1 1-< 3 3-<6 >6 BNH 24.5 24.5 2.4 20.4-28.0 27.9 26.2 7.2 19.6-60.7 24.7 24.2 4.2 17.9-32.5 27.5 29.4 4.9 20.6-33.0 F value= 2.1,p =.10 PFOS (RRM) 0 -< 1 1 -< 3 3 -< 6 >6 0 -< 1 1 -< 3 3 -< 6 >6 0 -< 1 I-< 3 3 -< 6 >6 0 -< 1 1-< 3 3 -< 6 >6 0 -< 1 1-< 3 3 -< 6 >6 Table 17 (continued) Mean Med SD Range Cigarettes 6.0 9.0 10.5 7.7 0.0 11.2 11.6 12.0 11.8 0.6 0.0 1.3 F=-1.8,P=.16 0.0-25.0 0.0-35.0 0.0-40.0 0.0-3.0 BLTN 17.0 16.0 3.1 14.0-22.0 15.8 15.0 3.8 8.0-26.0 17.0 17.0 3.8 10.0-23.0 14.4 14.0 4.0 10.0-21.0 F value= 1.1,p = .35 Creatinine 1.0 1.0 0.1 0.8-1.1 1.0 0.9 0.2 0.7-1.6 0.9 0.9 0.1 0.7-1.2 1.1 1.2 0.4 0.6-1.6 F value= 2.7,p =.05 Glucose 82 82 7 70-93 89 84 29 62-260 81 82 12 66-112 87 83 16 71-105 F value= 0.8,p =.52 AlkalinePhosRhatase 82 82 14 66-103 88 89 25 49-146 85 82 21 32-124 88 74 29 63-136 F value= 0.3,p =.84 PFOS (ppm) 0 -< 1 1-< 3 3 -< 6 >6 0 -< 1 1-< 3 3 -< 6 >6 0 -< 1 1-< 3 3 -< 6 >6 0 -< 1 1-< 3 3 -< 6 >6 0 -< 1 1-< 3 3 -< 6 >6 Table 17 (continued) Mean Med SD Range GGT 38 28 27 23-111 53 41 49 2-293 39 39 15 21-80 48 49 19 32-79 F value= 0.9,p =.44 AST 31 25 23 17-96 30 27 14 14-90 25 24 6 13-37 31 30 4 26-37 F value= 1.2,p =.31 ALT 52 48 21 36-108 48 43 24 25-183 42 41 7 30-59 54 57 20 29-82 F value=1.1, p =.36 TotalBilirubin 0.86 0.70 0.45 0.40-2.00 0.67 0.65 0.28 0.20-1.30 0.65 0.60 0.31 6.20-1.40 0.68 0.70 0.15 0.50-0.90 F value= 1.2,p =.30 DirectBilirubin 0.22 0.20 0.04 0.20-0.30 0.20 0.20 0.05 0.10-0.30 0.22 0.20 0.04 0.20-0.30 0.22 0.20 0.04 0.20-0.30 F value= 0.6,p =.63 PFOS (pi2m) 0 -< 1 1 -< 3 3 -< 6 >6 0 -< 1 1-< 3 3 -< 6 >6 0 -< 1 1-< 3 3 -< 6 >6 0 -< 1 1-< 3 3 -< 6 >6 0 -< 1 1-< 3 3-<6 >6 Table 17 (continued) Mean Med SD Range Cholesterol 213 207 33 220 227 42 217 214 29 200- 208 34 F value= 0.5,p =.69 180-290 144-315 171-270 160-240 LDL 129 128 22 106-177 136 146 39 65-228 139 135 29 84-190 129 130 29 95-172 F value= 0.3,p =.85 HDL 52 57 12 31-63 50 46 15 28-94 46 48 12 23-74 45 46 10 34-61 F value= 0.6,p =.64 Triglycerides 157 121 167 41-622 163 129 118 41-651 156 138 97 34-413 128 151 52 64-187 F value= 0.1,p = .94 Hematocrit 47 48 2 44-49 46 46 3 39-52 47 47 2 43-52 47 48 1 45-49 F value= 2.3,p =.08 PFOS (Rpm) 0 -< 1 1-< 3 3 -< 6 >6 0 -< 1 1-< 3 3 -< 6 >6 0 -< 1 1-< 3 3 -< 6 >6 0- < 1 1-< 3 3 -< 6 >6 0 -< 1 1-< 3 3-<6 >6 Table 17 (continued) Mean Med SD Ranize Hemoglobin 15.6 15.8 0.5 15.2 15.3 0.9 15.6 15.6 0.7 15.5 15.4 0.7 F value= 1.8,p =.16 14.6-16.1 13.0-17.1 13.8-17.4 14.8-16.2 RBC 4.9 5.0 0.3 4.3-5.2 4.9 4.9 0.3 4.3-5.7 5.0 5.0 0.2 4.6-5.4 5.0 5.2 0.7 4.0-5.7 F value= 0.4, p = .74 MCH 32.0 31.7 1.1 30.8-33.9 30.8 30.8 1.4 27.3-33.2 31.2 31.8 1.5 26.0-33.3 31.1 30.2 3.4 28.2-36.9 F value= 1.9, p =.14 MCHC 32.9 33.1 0.8 31.9-34.5 33.0 33.1 0.7 31.7-34.5 32.9 32.8 0.7 31.3-34.2 33.1 33.3 0.8 32.2-34.0 Fvalue=0.2, p=.93 mcv 97 95 5 92-106 93 93 4 83-101 95 95 5 81-104 94 91 12 85-115 F value= 1.9, p =.13 PFOS (ppm) Table 17 (continued) Mean Med SD Range 0 -< 1 1 -< 3 3 -< 6 >6 WBC 6.7 6.5 1.8 4.4-9.4 7.3 0.9 2.2 3.6-15.5 7.7 7.5 2.3 4.1-13.3 7.1 6.9 0.6 6.4-7.8 F value= 0.7, p =.59 0 -< 1 1 -< 3 3 -< 6 >6 Platelets 243 230 43 189-309 234 227 44 153-365 229 230 50 132-344 177 182 29 143-205F value= 2.7,p =.05 1. Significantldyifferent(p< .05)thantheremainingthreePFOS exposurecategories. 2. Significantdliyfferen(tp<.05) thanthe0 -< Ippm PFOS category. 3. Significantldyifferen(tp< .05)thantheI -< 3 ppm PFOS category. 4. Significantdliyfferen(tp<.05) thanthe3 -< 6 ppm PFOS category. 5. Significantdliyfferen(tp< .05)thanthe> 6ppm PFOS category. Sample sizes: PFOS Level Both Locations 0 -< I ppm 10 1 - < 3 ppm 46 3 -< 6 ppm 27 > 6 ppm 5 88 AntweLp 9 21 18 2 50 Decatur 1 25 9 3 38 Table 18 MultivariablReegressionof Serum Chemistriesand HematologicalParameters in RelationtoPFOS AdjustingforAge, Alcohol,BNE and Cigarettes, Antwerp and DecaturData Combined, For Those Employees Who Had Hormone Measurements in 1995 AlkalinePhosRhatase Variable Intercept PFOS Age Alcohol BNE Cigarettes Parameter 64.57 0.002 0.13 -4.17 0.60 0.60 R 2 = .22 SE 15.23 .1.11 0.30 1.75 0.39 0.20 Adj R 2 R value .001 .99 .66 .02 .13 .004 .17 InGGT Vaziable Intercept PFOS Age Alcohol BNU Cigarettes Parameter 1.9570 0.0077 0.0157 0.1043 0.0341 0.0096 R 2 = .20 SE R valu 0.4203 .0001 0.0301 .80 0.0084 .07 0.0484 .03 0.0107 .002 0.0056 .09 Adj R 2 .15 AST Variable Intercept PFOS Age Alcohol BNU Cigarettes Parameter 16.13 -0.13 0.006 1.02 0.51 -0.20 R 2 = .08 SE 9.90 .72 0.20 1.14 0.25 0.13 Adj R 2 = .02 R value .11 .86 .98 .37 .04 .13 Table 18 (continued) ALT Variable Intercept PFOS Age Alcohol BNU Cigarettes Parameter 25.19 -0.12 -0.04 0.20 0.95 -0.20 R 2=.Io SE 14.22 1.04 0.28 1.64 0.36 0.19 Adj R 2 =.04 12value .08 .90 .89 .90 .01 .29 InTotalBilirubin Variable Intercept PFOS pFOS2 Age Alcohol BMI Cigarettes Parameter 0.6133 -0.0885 0.0073 -0.0025 0.0235 -0.0270 -0.0162 R 2 = .39 SE 0.2726 0.0518 0.0048 0.0054 0.0309 0.0068 0.0036 Adj R 2 R value .03 .09 .13 .64 .45 .0002 .0()()l .34 DirectBilirubin Variable Intercept PFOS Age Alcohol BNE Cigarettes Parameter 0.225 0.001 0.0007 0.004 -0.002 -0.0003 R 2 =.Og SE R value 0.0335 .0001 0.002 .64 0.0007 .31 0.004 .26 0.0009 0.05 0.0004 .44 Adj R 2 .03 Table 18 (continued) BLTN Variable Intercept PFOS Age Alcohol BNU Cigarettes Parameter 18.73 -0.10 -0.05 0.37 -0.003 -0.05 R 2 =.08 SE 2.72 0.20 0.05 0.31 0.07 0.04 Adj R2 =.02 R value .0001 .60 .35 .24 .97 .14 Creatinine Variable Intercept PFOS pFOS2 Age Alcohol BNH Cigarettes Parameter 0.5031 -0.0488 0.0051 0.0086 -0.0119 0.0090 -0.0017 R 2 = .37 SE R value 0.1178 .0001 0.0223 .03 0.0020 .01 0.0023 .0004 0.0133 .38 0.0029 .003 0.0016 .28 Adj R 2 .32 InGlucose Variable Intercept PFOS Age Alcohol BMI Cijzarettes Parameter 3.8241 -0.0029 0.0051 -0.0052 0.0166 -0.0018 R' = .42 SE 0.1090 0.0079 0.0022 0.0125 0.0028 0.0014 Adj R 2 =.38 R value .0001 .71 .02 .68 .0001 .22 Table 18 (continued) Cholesterol Variable Intercept PFOS Age Alcohol Bl@U Cigarettes Parameter 198.04. -2.83 1.26 -1.32 -0.73 -0.07 R 2 =.09 SE 26.88 1.97 0.54 3.09 0.68 0.35 Adj R 2 R value .0001 .15 .02 .67 .29 .85 .03 LDL Variable Intercept PFOS Age Alcohol BNH Cigarettes Parameter 152.37 -0.45 0.70 -5.58 -1.19 -0.59 R 2 = .14 SE 23.90 1.74 0.48 2.75 0.61 0.32 Adj R 2 12value .0001 .80 .14 .05 .05 .07 .08 HDL Variable Intercept PFOS Age Alcohol BNU Cigarettes Parameter 77.68 -0.66 -0.31 2.68 -0.66 -0.07 R'=.32 SE 8.51 0.62 0.17 0.98 0.22 0.11 AdjR 2 =.28 R value .0001 .29 .07 .008 .003 .56 Table 18 (continued) Triglycerides Variable Intercept PFOS Age Alcohol BNE Cigarettes Parameter -178.52 -7.89 4.22 9.90 6.07 3.17 R' = .32 SE 71.97 5.26 1.44 8.28 1.83 0.95 Adj R 2 =.28 p value .02 .14 .005 .24 .001 .001 Hematocrit Variable Intercept PFOS Age Alcohol BNfl Cigarettes Parameter 48-03 -0.05 0.02 -0.003 -0.10 0.04 R' = .12 SE 1.66 0.12 0.03 0.19 0.04 0.02 Adj R 2 R value .0001 .70 .48 .99 .02 .05 .06 Hemoglobin Variable Intercept PFOS Age Alcohol BNU Cigarettes Parameter 15.76 -0.02 -0.04 0.01 -0.03 0.009 R' = .09 SE 0.58 0.04 0.07 0.01 0.01 0.008 R value .0001 .67 .28 .58 .03 .25 Adj R 2 =.03 Table 18 (continued) MCH Variable Intercept PFOS Age Alcohol BNU Cigarettes Parameter 33.52 0.04 -0.006 0.11 -0.10 0.03 R 2 =.24 SE p value 1.05 .0001 0.08 .59 0.02 .79 0.12 .35 0.03 .0003 0.01 ..03 AdjR2 = .20 MCHC Variable Intercept PFOS Age Alcohol BNII Cigarettes Parameter 32.87 -0.001 0.008 -0.08 -0.0006 -0.01 R 2 = .07 SE 0.50 .037 0.01 0.06 0.01 0.007 Adj R 2 p value .0001 .98 .42 .19 .96 0.08 .02 mcv Variable Intercept PFOS Age Alcohol BNH Cigarettes Parameter 101.97 0.14 -0.04 0.56 -0.31 0.12 R 2 = .28 SE 3.36 0.25 0.07 0.39 0.09 0.04 Adj R 2 p value .0001 .56 .53 .15 .0005 0.007 .23 Table 18 (continued) RBC Variable Intercept PFOS Age Alcohol BNU Cigarr,ttes Parameter 4.673 -0.009 0.005 -0.026 0.006 -0.002 R 2 = .08 SE 0.214 0.016 0.004 0.025 0.005 0.003 Adj R 2 R value .0001 .58 .28 .29 .24 .48 .02 Platelets Variable Intercept PFOS Age Alcohol BNU Cigarettes Parameter 320.83 -6.73 -0.94 -6.95 -1.26 0.43 R 2 =.18 SE 32.21 2.36 0.64 3.70 0.82 0.43 Adj R 2 R value .0001 .006 .15 .06 .13 .32 .13 WBC Variable Intercept PFOS Age Alcohol BNH Cigarettes Parameter 3.24 -0.03 0.07 0.03 0.03 0.09 R 2 = .35 SE 1.32 0.10 0.03 0.15 0.03 0.02 Adj R 2 =.31 R value .02 .74 .01 .82 .42 .0001 Table 19 Mean, Median (Med),StandardDeviation(SD) ofMean and Range ofPFOS, Hormonal Measurements forN 88 Employees, Antwerp and DecaturCombined, 1995 PFOS (RRM) Mean Med SD Range 0 -< 1 1-< 3 3 -< 6 >6 Cortisol 19.3 17.5 7.0-29.0 17.7 18.0 7.2 1.0-42.0 21.4 23.0 7.2 7.0-31.0 17.0 19.0 6.2 9.0-23.0 F = 1.7,p =.18 0 -< 1 1 -< 3 3 -< 6 >6 DHEA-S 3883" 358 168 234"4 210 95 316' 318 106 1942 190 19 F = 8.3,p =.0001 88-605 69-460 90-530 176-215 0 -< 1 1-< 3 3 -< 6 >6 Estradiol 67.1 67.0 12.8 60.3 59.0 15.2 60.5 61.0 10.1 64.8 65.0 18.7 F = 0.8,p =.49 50.0-87.0 35.0-101.0 42.0-81.0 47.0-92.0 0 -< 1 1-< 3 3 -< 6 >6 FSH 3.8 3.5 1.5 2.0-6.0 5.6 4.0 4.2 1.0-26.0 5.6 4.0 3.9 2.0-18.0 6.6 6.0 3.4 3.0-12.0 F value= 0.8,p = 0.48 0 -< 1 1-< 3 3 -< 6 >6 17-Hydroxyprogesterone 170 164 41 121-245 131 123 52 53-294 150 153 52 65-245 119 98 4590-197 F value= 2.4,p = .08 PFOS (12RM) 0 -< 1 1-< 3 3 -< 6 >6 0 -< 1 1-< 3 3 -< 6 >6 0 -< 1 1 -< 3 3 -< 6 >6 0 -< 1 1-< 3 3 -< 6 >6 0- <1 1 -< 3 3 -< 6 >6 Table 19 (continued) Mean Med SD Range LH 3.8 4.0 0.9 4.6 4.0 3.0 4.6 5.0 1.9 4.8 5.0 1.3 F value= 0.3,p =.81 2.0-5.0 1.0-21.0 2.0-9.0 3.0-6.0 Prolactin 13.5 13.0 7.0 6.0-29.0 11.8 11.0 5.0 3.0-30.0 13.4 10.0 7.9 5.0-39.0 13.6 10.0 6.3 9.0-24.0 F value= 0.5, p =.67 SHBG 0.9 0.9 0.3 1.0 0.9 0.4 1.0 0.9 0.3 1.2 1.3 0.6 F = 1.1,p =.35 0.5-1.3 0.4-1.9 0.4-1.7 0.6-2.1 Free testosterone 20.5' 20.2 5.2 10.2-28.2 16.22 16.1 3.3 8.9-27.1 17.7 18.2 3.2 12.2-25.2 17.5 17.7 2.0 15.3-20.5 F value= 4.5,p =.006 Bound testosterone 7393 757 175 5281094 5802,4 589 676 3 659 110 278-762 171 410-1039 711 752 160 462-883 F value= 5.2,p = .003 Table 19 (continued) PFOS (P-Rm) 0 -< 1 1-< 3 3 -< 6 >6 Mean Med SD Ranize TSH 1.9 1.4 1.3 0.6-4.5 1.0 1.5 1.4 0.5-8.1 1.5 1.4 0.8 0.5-3.4 2.0 1.6 1.2 0.7-3.8 F value= 0.6,p =.62 Sample sizes: PFOS Level Both Locations 0 -< I ppm 10 1 - < 3 ppm 46 3 - < 6 ppm 27 2:6 ppm 5 88 Antwelp 9 21 18 2 50 Decatur 1 25 9 3 38 Table 20 MultivariablReegressionAnalysisof Hormones inRelationtoPFOS AdjustingforAge, Alcohol,B@E and Cigarettes, Antwerp and DecaturData Combined, 1995 Cortisol Variable Intercept PFOS Age 'Alcohol BNU Cigarettes Parameter 27.13 0.27 -0.10 1.56 -0.25 0.01 R 2 =.22 SE 4.84 0.35 0.10 0.56 0.12 0.06 AdjR'=.17 p value .0001 .45 .31 .006 .04 .87 DBEAS Variable Intercept PFOS Age Alcohol BNU Cigarettes Parameter 499.17 -2.95 -5.30 17.88 -1.82 2.25 R' = .28 SE 76.98 5.63 1.54 8.84 1.95 1.01 Adj R' p value .0001 .60 .0009 .05 .35 .03 .24 Estradiol Variable Intercept PFOS PFOS' Age Alcohol BMI Cigarettes Parameter 53.56 -3.82 0.44 -0.13 2.42 0.57 0.07 R'=.18 SE 9.76 1.85 0.17 0.19 1.10 0.24 0.13 Adj R'=.12 p value .0001 .04 .01 .51 .03 .02 .58 Table 20 (continued) Estradio(lwithoutemrloyeeC) Variable Intercept PFOS pFOS2 Age Alcohol BNE Cigarettes Parameter 53.43 -3.56 0.40 -0.13 2.43 0.56 0.69 R'=.13 SE 9.84 2.39 0.28 0.19 1.11 0.25 0.13 Adj R' p value .0001 .14 .15 .51 .03 .03 .60 .06 FSH Variable Intercept PFOS Age Alcohol BNH Cigarettes Parameter 3.64 0.02 0.14 0.04 -0.13 0.005 R 2 =.Io SE 2.79 0.20 0.06 0.32 0.07 0.04 Adj R 2 R value .20 .91 .02 .89 .07 .90 .05 17-HydroxyRrogesterone Variable Intercept PFOS Age Alcohol BNE Cigarettes Parameter 306.10 -0.04 -2.13 -0.76 -3.47 0.79 R 2 = .33 SE 32.69 2.36 0.67 3.68 0.82 0.42 Adj R 2 = .28 R value .0001 .99 .002 .84 .0001 .07 Table 20 (continued) LH Variable Intercept PFOS Age Alcohol BNH Cigarettes Parameter 5.65 0.05 -0.02 -0.24 -0.03 0.03 R' = .04 SE 1.86 0.13 0.04 0.21 0.05 0.02 Adj R 2 =.02 R value .003 .69 .69 .26 .56 .21 Prolactin Variable Intercept PFOS Age Alcohol BNE Cigarettes Parameter 16.67 0.34 -0.15 1.75 0.004 -0.14 R' = .31 SE 3.99 0.29 0.08 0.46 0.10 0.05 Adj R 2 R value .0001 .25 .07 .0003 .97 .01 .27 SBBG Variable Intercept PFOS Age Alcohol BNE Cigarettes Parameter 0.03 0.005 0.02 -0.005 0.005 0.004 R 2 = .28 SE 0.24 0.02 0.005 0.03 0.006 0.003 Adj R 2 R value .89 .77 .0001 .86 .40 .19 .23 Table 20 (continued) Free Testosterone Variable Intercept PFOS Age Alcohol BNH Cigarettes Parameter 27.37 0.02 -0.14 -0.11 -0.1.9 0.01 R 2 = .19 SE 2.57 0.19 0.05 0.30 0.06 0.03 Adj R 2 p value .0001 .90 .01 .69 .005 .68 .14 Bound Testosterone Variable Intercept PFOS Age Alcohol BNH Cigarettes Parameter 993.88 6.91 -2.43 7.41 -11.43 1.22 R 2 = .28 SE 100.93 7.28 2.06 11.37 2.52 1.31 Adj R2 =.2j- p value .0001 .35 .24 .52 .0001 .35 TSH Variable Intercept PFOS Age Alcohol BNH Cigarettes Parameter -0.873 0.004 0.003 0.078 0.096 -0.011 R 2 = .23 SE 0.826 0.060 0.016 0.095 0.021 0.011 Adj R 2 p value .29 .95 .85 .41 .0001 .32 .18 FIGURE Scattec Plot of Estcadiot and PE)OS, Both Locations Combined, EstradoolBy PF:OS 1995 110001) 100000 1"000000000 90.000 80.000 70.000 60.000 50.000 40.OW roe was a a % s 30.000 .000 2.000 4.000 6.000 1 8.000 PFOS 10.000 12.000 14.000 - Po"trial Rt dogrooq - Unear Rt P*WMW Rt dogres-2 EstradW - 66.4703 - 3.60448 PFOS + 0.42197 PFOSA2 Summary of Rt RSquare RSquare Ad) Root Mean SquareErwr Mean d R"prse Ob"Maftm (O(Sum VIP) 0.07618 0.06"23 13.33314 61.30" as Source moclei Error C Total Ana"s ofVaftve DF Sum of Squares Mean Square F Rago 2 1245.701 622.850 3.5036 85 15110.663 177.773 Prob>F 87 16356.364 0.0345 Term lntgmgpt PFOS PFOSA 2 Parameter Esdmates Esdmato 66.470276 -3.604477 0.4219692 StclError 3.632698 1.7997 0.167705 t Ratio 18.30 -ZOO 2.S2 Prob@-ftl <.0001 0.0484 0.0137 Estradiol- 59.7222 + O@57198 PFOS Summary of Fit RSquare RSquare Adi Root Mean Square Error Mean of Response Observadons (orSum Wgts) 0.00735 -0.00419 13.74017 61.36364 88 Source Mod4W Error C Total AnalysisOfVadance OF Sum ofSquares Mean Square F Rado 1 120.226 120.226 0.6368 86 16236.138 188.792 Pmb:..F 87 16358.364 0.4271 Term Intercept PFOS ParameterEsdmatn Esdmate 59.722236 0.5719843 SW Error 2.525093 0.716766 t Rado 23.65 0.80 Pmb>ftl <.Oool 0.4271 FIGURE 2 Scatter Plot of Estcadiol and PFOS, Both Locations Cominbed, 1995 GStradiolBy PF@OS Without Employee A 110000 100.000 90.000 80.000 'a 70.000 60.000 case a 50.000 40.000 30.000 .000 2.000 4.000 6.000 8.000 10.000 12.000 14. PFOS - PolynorrdRatldogr".2 - UnearRt PolywffialRt dogree-2 Estadol m 65.8629 - 3.1OSSO PFOS + 0.34755 PF;OSA2 Summary ofFit RSquare RSquare Adl Root Me= Square Ermr Mean of Response Obswvadons (orSum Wgts) 0.020652 -0.00277 13.40325 61.01149 87 Source Model Error C Total An*Ws ofVariance DF Sum of Squares Mean Square F Ratio 2 316.639 158.320 0.8813 84 15090.349 179.647 Prob>F 86 15406.989 0.4180 Term Intercept PFOS PFOSA2 Parameter Esdmatos Estimate 65.862871 -3.105693 0.3475472 Std Error 4.074112 2.339491 0.278213 t Rado 16.17 -1.33 1.25 Pmb>pl <.0001 0.1879 0.2151 LinearFft Estradiol- 62.027 1 - 0 3686 1 PFOS Summary of Fit RSquare RSquare Adi Root Mean Square Error Mean of Response Observations (orSum Wgts) 0.002356 -0.00938 13.44737 61.01149 87 Source Model Error C Total Analysisof Variance DF Sum ofSquares Mean Square F Rado 1 36.295 36.295 0.2007 as 15370.694 180.832 Prob>F as 15406.989 0.6553 TWM IntereW PFOS Pwamew Es*mft 62-027069 -0.368607 Esdmates SW Eme 2.686488 0.822768 t Rado 23.09 -0.45 Pwb.-.ftl <.Oool 0.6553 APPENDIX A TotalBilirubiannd PFOS ScatterPlots DRAFT Scattec Plot oE TotaL Bilicubin and PFOS, Both Locations Combined, 1995 TotalBifirubiBny PFOS 300 2.50 2.00 C-! 1.50 1.00 se 0 0.50 00 0.00 .00 2.00 4.00 6.00 8.00 10.00 12.00 14.00 PFOS - UnearFit - PolynomiaRlt dogme-2 Unew Fit TotalBlOrubin- 0.78247- 0.02927PFOS Summary of Fit RSquare RSqtjaroAdi Root Mean Square Error Mean of Response Observations(orSum Wgts) 0.022279 0.016692 0.363488 0.7186" 177 Source Model Error C Total An*Ws ofVariance DF Sum of Squares Mean Square F Ratio 1 0.526856 0.526856 3.9876 175 23.121618 0.132124 Prob>F 176 23.648475 0.0474 Term Intercept PFOS ParameterEstimates Estimate 0.7824732 -0.029269 Std Error 0.04205 0.014657 t Ratio 18.61 -2.00 Pmb>pl <.0001 0.0474 PolynomialFitdogree-2 TotalBilrubin 0.86632- 0.09918PFOS + 0.00846PFOSA 2 Summary of Fit RSquare RSquare Adj Root Mean Square Error Mean of Response Observations (orSum Wgts) 0.051674 0.040773 0.359009 0.718644 177 Source Model Error C Total AnalysisofVaOance DF Sum of Squares Mean Square F Ratio 2 1.222006 0.611003 4.7406 174 22.426468 0.12assa Prob>F 176 23.648475 0.0099 Term lntempt PFOS PFOSA2 Parameter Esdmates Esdmide O.SOWIS -0.099182 0.008459 SW Erfor 0.054748 0.033404 0.003642 t Rado 15.81 -Z97 2.32 Prob>ftl <.0001 0.0034 0.0214 Scattec Plot of Total Bilicubin aridPFOS, Antwecp, 1995 Total13ilirubBiyn PFOS 300 2.50 2.00 c,3 1.50 1.00 o.so .00 2.00 4.00 6.00 8.00 10.00 12.00 14.00 PFOS - Unew Fit - PolynomiaRlt dogres-2 Unew Fit TotalBilrubinm 0.92001- 0.02927 PFOS Summary ofFit RSqtjare RSquare Adi Root Me= Square Error Mean of Response Observadons (orSum Wgts) 0.017786 0.006365 0.407279 0.863636 as Source Model Error C Total AnalysisofVariance DF Sum ofSquares Mean Square F Ratio 1 0.258313 0.258313 1.5573 86 14.265323 0.165876 Prob>F 87 14.523636 0.2155 Term Intercept PFOS Parameter Estimates Estimate Std Error 0.9200069 0.062664 -0.029266 0.023452 tRato 14.68 -1.25 Prob>Rl <.0001 0.2155 PolynomialFitdogree-2 TotalBigrubin- 0.96548 - 0.07872 PFOS + 0.00697 PFOSA 2 Summary of Fit RSquare RSquare Adj Root Mean Square Error Mean ofResponse Observafions (orSum Wgts) 0.027505 0.004623 0.407635 0.863636 88 Source Model Error C Total Analysisof Vadance DF Sum of Squares Mean Square F Ratio 2 0.399470 0.199735 1.2020 as 14.124166 0.166167 Prob>F 87 14.523636 0.3056 Term lnwmopt PFOS PFOS^2 Parameter Estimates Esdmale 0.9654789 -0.078719 0.0060749 SW Error 0.07979 O.OSW65 0.0075N t Ratio 12.10 -1.34 0.92 Prob>ftl <.0001 0.1825 0.35M Scattec Plot of TotaL Bilicubin and PFOS, Decatuc, 1995 TotalBilirubiBny PFOS 300 2.50 2.00 1.50 co 1.00 0.50 0.00 .00 2.00 4.00 6.00 S.@ PFOS 10-00 12.00 14.00 - Unew Rt - PolrmniWFitdogroo-2 Unew Rt TotalBiliubin- 0.59712- 0.00898 PFOS Summary of Fit RSquare RSquare Adj Root Mean Square Error Mom of Response Observations(orSum Wgts) 0.004472 -0.00697 0.249626 0.575281 89 Source Model Error C Total Ana"s ofVadance DF Sum ofSquares Mom Square F Ratio 1 0.0243540 0.024354 0.3908 87 5.4212639 0.062313 Prob>F 88 5."56180 0.5335 Term lntemept PFOS Parameter Esdmates Estimate 0.5971232 -0.008979 Std Effor 0.043827 0.014363 t Redo 13.62 -0.63 Pmb>ftl <.0001 0.5335 Po"tTgal Fitdogres-2 TotalBiffrubi-n0.66974- 0.05867PFOS + 0.00518PFOSA 2 Summary ofFit RSquare 0.032545 RSquare Adi Root Mean Square Error Mean of Response Observations (orSum Wgts) 0.010046 0.247508 0.575281 89 Source Model Error C Total AnalysisofVadance DF Sum of Squares Mean Square F Ratio 2 0.1772262 0.088613 1.4465 86 5.2683918 0.061260 Prob>F 88 5."56180 0.2411 Term Intercept PFOS PFOSA2 Parameter Esdmales Esdmate 0.6897418 -0-OSM2 0.0051833 Sid Enor 0.063258 0.034531 0.003281 t Rado 10.59 -1.70 1.58 Pmb>ftl <.0001 o.om 0.1178 Scattec Plot oE TotaL Bilicubin and PFOS, Both LocatLons CombLned, 1997 TotalBifirubBiyn PFOS 250 2.00 1.50 1.00 0.50 0.00 .00 2.00 4.00 6.00 8.00 10.00 12.00 PFOS Unew Rt PolynordalFitdogroo=2 Unew Fit TotalBlinibin- 0.7185- 0.02683 PFOS Summary of Fit RSquare RSquare Adi Root Mean Square Error Mean of Response ObservwJons (orSum Wgts) 0.016221 0.009483 0.322046 0.672973 148 Source Model Ermr C Total AnalysisofVadance DF Sum of Squares Mean Square F Ratio 1 0.249674 0.249674 2.4073 146 15.142218 0.103714 Prob>F 147 15.391892 0.1229 Term Intercept PFOS ParameterEstimates Estimate 0.7184974 -0.025825 Std Error 0.039518 0.016645 t Rado 18.18 -1.55 Pmb>pl <.0001 0.1229 PolynomialFitdogree-2 TotalBifirubin 0.78963 - 0.10456 PFOS + 0.012PFOSA 2 Summary ofFtt RSquare RSquare Ad] 0.045789 0.032628 Root Mean Square Error Mean of Response Observafions (orSum Wgts) 0.318261 O@672973 148 Source Model Error C Total Analysisof Variance DF Sum of Squares Mean Square F Ratio 2 0.704787 0.352393 3.4790 145 14.687105 0.101290 Prob>F 147 15.391892 0.0334 Term intwcmx PF-OS PFOSA2 Parameter Esdmates Esdmate 0.7896264 -0.104564 0.0120049 SW Error 0.05149 0.040625 0.005663 t Rado 15.34 -2.57 2.12 Prob>ftl <.0001 0.0111 0.0357 ScatteC PLOT of Totdt Bilicubin and PFOS, Antwerp, 1997 2.50 TotalBilirubiBny PFOS 2.00 1.50 i.oo 0.50 ago a a a .00 2.00 4.00 6.00 8.00 10.00 PFOS L Unew Fit PolywffdalFitdogr".2 Unear Rt TotalBilrubin 0.8517- 0.03647 PFOS Summary of Fit RSqtjare RSquare Adi Root Mean Square Error Mean of Response observations (orSum Wgts) 0.014291 -0.00161 0.385334 0.796875 64 Source Model Ermr C Total Analysisd Vaftnco DF Sum of Squares Mean Square F Ratio 1 0.1334670 0.133467 0.8989 62 9.2059080 0.148482 Prob>F 63 9.3393750 0.3468 Term Intercept PFOS Parameter Estimates Estfinale 0.8516999 -0.036474 Std Error 0.075259 0.038471 t Ratio 11.32 -0.96 Prob>Rl <.0001 0.3468 PolynomialFitdogr".2 Total SiOrubin 0.9635 - 0.22847 PFOS + 0.0462 PFOSA 2 Summary of Fit RSquare RSquare Adi 0.051848 0.020761 Root Mean Square Error Mean of Response Ob"rvaflons (orSum Wgis) 0.318261 0.672973 148 Source Model Error C Totw AnalysisofVariance DF Sum ofSquares Mean Square F Rato 2 0.704787 0.352393 3.4790 145 14.687105 0.101290 Prob>F 147 15.391892 0.0334 TWM PFOG PFOSA2 Parameter Esdmates Esdmate 0.7896264 -0.104564 0.0120040 SW Error 0.05149 0.040as 0.00560 tRa#o 15-34 -2.57 2.12 Prob.-.pl -c.0001 0.0111 0.0367 Scattec PlOt of Totdl Bilicubin and PFOS, Antwecp, 1997 2.50 TotalBilirubiBny PFOS 2.00 1.50 J.C)O 0.60 .00 2.00 4.00 6.00 8.00 10.00 PFOS Unew Rt PolywffdalRt dogree-2 Unear Rt TotalBilrubin.,0.8617- 0.03647 PFOS Summary of Rt RSquare RScpjare Adj Root Mean Square Error Mean of Response Observagons (orSum Wgts) 0.014291 -0.00161 0.385334 0.796875 64 source Model Error C Total Ana"s d Vadance DF Sum of Squares Mean Square F Rado 1 0.1334670 0.133467 0.8989 62 9.2069080 0.148482 Prob>F 63 9.3393750 0.3468 Term Intercept PFOS Parameter Esdmates Esdmate 0.8516999 -0.036474 Std Error 0.075259 0.038471 tRado 11.32 -0.96 Pmb>@l <.0001 0.3468 PolynarrdaFlitdogr".2 Total SiUrubin 0.9635 - 0.22847 PFOS + 0.0462 PFOSA 2 Summary of Fit RSquare RSquare Adi 0.051848 0.020761 Root Mean Square Error Mean of Respon3G Observadons (orSum Wgts) 0.381007 0.796875 64 Source Model Error C Total Analysisof Variance OF Sum of Squares Mean Square F Ratio 2 0.4842255 0.242113 1.6678 61 8.8551495 0.14SI66 Prob>F 63 9.3393750 0.1971 Term intempt PFOS PFOSA2 Parwmter Esdmate 0.963501 -022"68 0.0461951 Esdmates SW Effor 0.103492 0.1 0.029718 tRago 9.31 -1.77 I.SS Prob:..Pl -c.0001 0.0821 0.1253 SCatter Plot of Total BiLicubin and PFOS, Decatuc, 1997 TotalBilirubiBny PFOS 2.50 2.00 1.50 39 1.00 0.50 0.00 .00 2.00 4.00 6.00 8.00 10.00 PFOS Unew Fit PdynorWal Rt dogroeq Unew Rt TotalBilrubin O.SGWS - 0.00894 PFos Summary ofRt RSquare RSquare Adj Root Mean Square Error Mean of Response Observations(orSum Wgts) 0.004924 -0.00721 0.229 0.578671 84 Source Model Error C Totw An*W.s ofVariance OF Sum ofSquares Mean Square F Ratio 1 0.0212775 0.021278 0.4057 82 4.3001510 0.052"1 Prob>F 83 4.3214286 0.5259 Term Intercept PFOS Parameter Esdmates Estimate Std Error 0.5960926 0.037161 -0.008937 0.01403 t Ratio 16.04 -0.64 Pmb>ftl <.0001 0.5259 PolynomialFitdogres-2 TotalBilrubinm 0.68287 - 0.09408 PFOS + 0.01143 PFOSA 2 Summary ofRt RSquare RSquare Adj 0.071405 0.048477 Root Mean Square Error Mean of Respon3o Observations (orSum Wgis) 0.222579 0.578571 84 Source Model Error C Total Analysisof Vadance DF Sum of Squares Mean Square F Ratio 2 0.3085734 0.154287 3.1143 81 4.0128552 0.049541 Prob>F 83 4.3214286 0.0498 Term lnwmw PFOS PFOS^2 Parameter Esdmates Esdmate d.68n676 -0.094082 0.011426 Sid Ermr 0.05102 0.0378M 0.004745 tRado 13.38 -2.48 2-41 Prob>pl -c.0001 0.0151 0.0183 FLGURE I Scattec Plot of Estcadiot and PFOS, Both Locations Combined, 1995 ES[f.idiaBly PFOS 11000() 100000 17000"0000(li 90.000 80.000 70.000 60.000 50.000 40.000 a ree Gas as % 30.000 .000 2-000 4.000 6.000 8.000 10.000 12.000 14.000 PFOS Po"oaM Rt doW"4 Unew Fk PokrAxdW Fk dogr"4 EsovxWl - 66.4703 - 3.60448 PFOS + 0.42197 PF;OSA2 Summary of Rt RSquare RSquare AcQ RocrtMe= Square Error Mean d A f" 4w1a-@06m9m--SM YAP) 0.07616 0.05"23 13.33314 61.30" Source mociai Error C Total Ana"s ofVaftnoo DF Sum of Squares Mean Square F Ratlo 2 1245.701 822.850 3.5036 as 15110.663 177.773 Prob>F 87 16356.3" 0.0345 TWM lntemept PFOS PFOSA 2 Parameter Esdm Es*nate 66.470276 -3.60"77 0.4219692 Std Error 3.632698 1.7997 0.167705 t Rado 10.30 -2.00 2.52 Prob@-PI -c.0001 0.0484 0.0137 Estradiol 59.7222 + 0 57198 PFOS Summary of Fit RSquare RSquare Adj Root Mean Square Error Mean of Response Observadons (ofSum Wgts) 0.00735 -0.00419 13.74017 61.36364 88 Source Model Error C Total An*313 OfVariance OF Sum ofSquares Mew Square F Ratio 1 120.226 120.226 o.sm as 16236.138 188.792 Probz..F 87 18356.364 0.4271 Term intercept PFOS Pwameter Eodmd" Estimate 59-722236 0.5719843 SW Error 2.525093 0.716766 t Ratio 23.65 0.80 Prob>ftl <.Oooi 0.4271 FIGURE 2 Scatter Plot of EstradioL and PFOS, Both Locations Cominbed, 1995 r:stradiBayl PFOS WithoUt Employee A 110000 100.000 90.000 80.000 67090000.0.-.0.o000o0C00)0o00o 60.000 F 50.000 40.000 % % 30.000 .000 2.000 4.000 6.000 8.000 10-000 12.000 1. PFOS - Pokrgw" Rtdogr"-2 - Unew Fk P*wr" Rtdogr".2 Di- 66.8= - 3.1060 PFOG + o.34755 pFor,,A2 Summaiy of Rt RSquare RSquwo Adl Rout Mom Square Error Mean d Response Obseriadons (orSum Wgto) 0.020562 -0-00277 13.40325 61.01149 87 source Model &mr C Totw Ana"s d Vaftnoo DF Sum ofSquwas Mom Square F RatJo 2 316.639 158.320 0.8813 84 15090.349 179.647 Prob>F aG 15406.989 0.4180 Term Intwcopt PFOS PFOSA 2 Pwameter Esdmates Esdmato 65.862871 -3-105693 0.3475472 Sid Emr 4.074112 2.339491 0.278213 tRado 16.17 -1.33 1.25 Prob>pl <.Oool 0.1879 0.2151 Line.irF,c E 31(adiol 62 02 71 - 0 3686 1 PFo.-i Summary of Fit RSquare RSquare Adi Root Mean Square Error Mean ofResponse Observadon3 (orSum Wgts) 0.002356 -0.00938 13.44737 61.01149 87 Source Model Erme C Total Analysisof Variance OF Sum ofSquares Mean Square F Ratio 1 36.295 36.295 0.2007 85 15370.694 180-832 Prob>F 86 lS406.989 0.6553 Tam [ntomqx PFOS &*nft SZO27069 -0.368607 SM Error 2.686488 0.82276a t Rado 23.09 -0-45 Prob.-.Pl -c.0001 0.6553 APPEi%4DEX B UnconjugatedBilirubiannd PFOS ScatterPlots DRAFT RSquare Adi Root mean Square Erro( Mean ofResponse observations (orSum Wgts) -002446 934987S 42 3=3 84 Source Model Error C Totai AnalySi3Of Variance DF Sum of Squares Mean Square F Rado 2 1.6333 0.8166 0.0093 al 7081.0334 87.4202 Prob>F 83 7082.6667 0.9907 TWM lntereep PFOS PFOSA2 Pwwn*WWMMISG Es*nm 42.334847 .02= 0.0272273 SW Ermr 2.143189 1.591892 0.199313 t Rado 19.85 -0.13 0.14 Pmb>ftl 4.0001 0.9002 0.8917 Scatter PLat of Unconjugated 'BLlicubinand PFOS, Both Locations Cofnbined, UnconjugatedbilirubBiyn PFOS 1995 '30 2.0 1.0 0.5 0.0- .00 2.00 4.00 6.00 8.00 10.00 12.00 14.00 PFOS Unear Fit PolynomialFitdogree-2 UnGw Fit Uncon@Qated birtrub-in0.56837- 0.0285 PFOS Summary ofFit RSquare RSqtjareAdj Root Mean Square Error Mean of Response Observagans (orSum Wgts) 0.024418 0.018843 0.337753 0.506215 177 Source Model Error C Total An*sis ofVariance DF Sum ofSquares Mean Square F Ratio 1 0.499660 0.499660 4.3800 175 19.963503 0.114077 Prob>F 176 20.463164 0.0378 Term Intercept PFOS Parameter Estimates Estimate 0.5683746 -0.028503 Std Error 0.039072 0.013619 tRatio 14.55 -2.09 Prob>@l <.0001 0.0378 Po@nomial Fitdegree-2 Unconjugated billrubi-n0.65239- 0.09941PFOS + 0.00858PFO S^2 Summary ofFit RSquare RSquare Adi 0.05,9356 0.048544 Root Mean Square Error moan ofResponse observations(orSum Wgts) 0.332602 0.506215 177 Source Model Error C Total AnalysisofVariance DF Sum of Squares Mean Square F Ratio 2 1.214616 0.607308 5.4898 174 19.248548 0.110624 Prob.,.,.F 176 20.463164 0.0049 Term lntomw PFOS PFOSA2 ParameterEsdmates Estimate 0.6523913 -0.009406 0.0085787 SW Error 0.060721 0.030947 0.003374 t Ratio 12.86 -3.21 2.54 Prob>pl c.0001 0.0016 0.0119 Scatter PLot of Unconjugated Bilirubin and PFOS, Antwecp, 1995 UnconjugatedbibrubinBy PFOS 3.0 2S 2.0 1.0 0.5-=seaa:n 0.0 .00 2.00 4.00 6.00 8.00 10.00 12.00 PFOS Unew Fit PolynorNalFitdogres-2 Unew Fit Uricon)jgatedbilrubi-n0.69447- 0.02604PFOS Summary ofFit RSquare RSquare Adj Root Mean Square Effor Mean of Response Observations(orSum Wgts) 0.018651 0.005217 0.374674 0.644318 Source Model Ermr C Total An*ds ofVarknoo DF Sum of Squares Mom Square F Ratio 1 0.204426 0.204426 1.4562 86 12.072733 0.140381 Prob>F 87 12.277159 0.2308 To= Intercept PFOS Parameter Esdmates Estmate 0.6944654 -0.026036 Std Error 0.057638 0.021575 tRatio 12.05 -1.21 Prob>ftl <.0001 0.2308 PolynomialRt dogreaq Unconjugated billrubi-n0.73919 - 0.07468 PFOS Summary ofFit R Sq uaro RSquare Adi + 0.00686 PFOSA2 0.027775 0.004899 Root Mean Square Error Mean of Response Observations (orSum Wgts) 0.374734 0.644318 88 Source Model Error C Total Analysisof Vatiance OF Sum of Squares Mean Square F Rato 2 0.340994 0.170497 1.2141 85 11.936165 0.140425 Prob>F 87 12.277159 0.3021 Term intwc"x PFOS PFOSA 2 Parameter Esdmatas Esftgo 0.73919M -0.074678 0.0068606 SW Enor 0.07335 0.063838 O.OM57 t Rado 10.08 -1.39 0.99 Prob>pl -c.0001 0.16M 0.3268 Scatter PLot of Unconjugated BiLicubLn and PFOS, Decatur, 1995 UnconjugatedbionibinBy PFOS 30 2.5 2.0 'E 1.0- 0.5 man m06 a 0.0 .00 2.00 4.00 6.00 8.00 10.00 12.00 14.00 PFOS Unew Fit PotynordalPt dogres-2 Unew Fit Unconpgated bilrubi-n 0.39803- 0.01166 PFOS Summary ofFit RSquare RSquare Adi Root Mean Square Error Mean of ReeMnse ObservafJons(orSum Wgts) 0.008475 -0.00292 0.235059 0.369663 89 Source Model Error C Total An*sls ofVariance DF Sum ofSquares Mean Square F Rado 1 0.0410886 0.041089 0.7436 87 4.8070013 0.055253 Prob>F 88 4.8480899 0.3909 Term lntempt P FO S Parameter Esdmates Esdfnate 0.3980339 -0.011663 Std Error 0.04127 0.013525 tRatio 9.64 -0.86 Prob>ftl -c.0001 0.3909 PolynomialFitdogree-2 Unconjugatedbillrubinn0.48279- 0.06966PFOS Summary ofFit RSquare + 0.00605PFOSA2 0.051431 RSquare Adi Root Mean Square Error Mean ofResponse Observations (orSum Wgts) 0.029371 0.231244 0.369663 89 Source Model Error C Total Analysisof Variance DF Sum of Squares Mean Square F Ratio 2 0.2493418 0.124671 2.3314 86 4.5987481 0.053474 Prob>F as 4.8480899 0.1033 Term lntorompt PFOG PFOS^2 Parameter Esdmates Esdrnate 0.4827917 -0.069683 O.OOGMS Sid Effor 0.050102 0.032262 0.003066 t Rago 8.17 -2.16 1.97 Pmb>#l -c.0001 0.0336 0.0517 Scattec Plot of Unconjugated Biticubin and PFos, Both Locations Combined, 1997 UnconjugatedbifirubBiyn PFOS 2.5 2.0 1.5 1.0 - 0.5- a own= 0.0 .00 .:ago 2.00 0 4.00 6.00 PFOS ---------- 8.00 10.00 Unear Fit PolynorrdaFlitdoW"-2 Unew Rt Unconimated bilrubinn 0.57745- 0.0194 PFOS Summary of Fit RSquare RSqtjwo Adj Root Mom Square Error Mean d Response observations(orSum Wgts) 0.012338 0.005573 0.277986 0.543243 148 Source Model Error C Totw An*sis d Vadance DF Sum ofSquare$ Mean Square F Ratio 1 0.140939 0.140939 1.8238 146 11.282304 0.077276 Prob>F 147 11.423243 0.1789 Term Intercept PFOS Parameter Estimates Estimate 0.577447 -0.019403 Std Error 0.034111 0.014368 t Ratio 16.93 -1.35 Pmb>@l <.0001 0.1789 PolynomialR dogree=2 Unconjugated billrubi-n0.64247- 0.09138PFOS Summary of Fit RSquare + 0.01097 PFOS^2 0.045634 RSquare Adi Root Mean Square Error Mean of Response Observations (orSum Wgts) 0.03247 0.274201 0.543243 148 Source Model Error C Total Analysisof Variance DF Sum of Squares Mean Square F Ratio 2 0.521284 0.260642 3.4666 145 10.901959 0.075186 Prob>F 147 11.423243 0.0338 Term lntwwpt PFOS PFOSA2 Parameter Estimates Esdmdo 0.6424713 -0.091384 0.0109746 SW Error 0.044361 0.03SWI 0.004879 t Rado 14.48 -asi 2.25 Pmb>ftl <.0001 0.0100 0.0260 Scattec Plot of Unconjugated Bilicubin and PFOS, Antwecp, 1997 Unconjugatedbili(ubBiyn PFOS 25 2.0 1.5 1.0 o.,s 0.0 .00 2.00 4.00 6.00 8.00 10.00 PFOS Unew Rt PolynorrdaRlt dogres.2 Unew Fit Uricon)jgatodbilrubi-n0.69161- 0.02872 PFOS Summary ofRt RSquare RSquare Adj Root Mean Square Error Mean d Response Observations(orSum Wgts) 0.01217 -0.00376 0.329151 0.648438 64 source Mocial Error C Total Analysids Vaftnoo DF Sum ofSquares Mean Square F Ratio 1 0.0827520 0.082752 0.7638 62 6.7170917 0.108340 Prob>F 63 6.7998437 0.3855 Term Intercept PFOS ParameterEstimates Estimate 0.6916073 -0.02872 StdError 0.064286 0.032862 t Ratio 10.76 -0.87 Prob>@l <.0001 0.3855 PolynomialFitdogree-2 Unconjugated bilirubi-n0.78708- 0.19268PFOS Summary of Fit RSqtjare RSqtjare Adi + 0.03945PFOSA2 0.049788 0.018634 Root Mean Square Error Mean of Response Obsorvabons (orSum Wgts) 0.325458 0.648438 64 Source Model Error C Total Analysisof Variance DF Sum of Squares Mean Square F Ratio 2 0.3385540 0.169277 1.5981 61 6.4612897 0.105923 Prob>F 63 6.7998437 0.2106 Term lnwc"A PFOS PFOSA2 Parameter Esdmates ENhWe 0.7870832 -0.192677 0.0394497 Std Ermr 0.088403 0.110395 0.025386 tRado 8.90 -1.75 1.55 Pmb>pl 4.0001 0.0860 0.1254 Scattec PLot of Unconjugated BLlicubin and PFOS, Decatuc, 1997 Unconjugated bilirub1i3nyPFOS 2.5 2.0 1.5 1.c)- 0.5- no= a a so a am a ones a a as 0.0 .00 2.00 4.00 6.00 8.00 10.00 PFOS Unew Rt - Po"rrJalRtdogr"-2 Unew Rt Uriconjugatedbilrubl-n 0.47268- 0.00489 PFOS Summary of Rt RSquare RSquare Adj Root Mean Square Erwr Mean ofR"ponse Observagons (orSum Wgts) 0.001886 -0.01029 0.202702 0.463095 84 Source Moclel Error C Total AnalysWd Vaftnee DF Sum ofSquares Mean Square F Ratlo 1 0.0063673 0.006367 0.1550 82 3.3692280 0.041088 Prob>F 83 3.3756952 0.6949 Term Intempt PFOS Parameter Esdmates Esdmate 0.47268 -0.004889 SW Error 0.032893 0.012419 tRdo 14.37 -0.39 Pmb>pl -c.0001 0.6949 PolyriorNaFld dogro"2 Unconjugatedbiurubin- 0.5544- 0.08508PFOS + 0.01076 PFOSA 2 Summary ofFit RSquare 0.077372 RSquare Adi Root Mean Square Error Mean ofResponse Observations (orSum Wgts) 0.054591 0.196086 0.463095 84 Source Model Error C Total AnalysisofVariance DF Sum ofSquares Mean Square F Ratio 2 0.2611750 0.130588 3.3963 al 3.1144202 0.038450 Prob>F 83 3.3755952 0.0383 Tam lnwcw PFOS PFOS^2 Parameter Esdmates Esdmate 0.5544015 -O.OBWS 0.01076" SW Ermr 0.0""7 0.03338 0.00418 tRado 12-33 -2.55 2.67 Pmb:.gl <.0001 0.0127 0.0119 APPENDIX C HDL atidPFOS ScatterPlots -.@@@,--I, DRAIFT Scattec Plot of HDL Cholestecol and PFOS, Both Locations Combined, 1995 HOL-CholesterolBy PFOS 100 90 80 70. 60 so 40 P%ir 8#-0dL & L%m 0 30- 20 10- 0 11 .00 2.00 4.00 6.00 8.00 10.00 12.00 14.00 PFOS Unew Rt PolynorriaRlt dogme-2 Unew Rt HDL-Oholmorol - 51.0197-1.17509 PFOS Summary of Fit RSqtjare RSquare Adj Root Mom Square Error Mean d Response Observadons (orSum Wgts) 0.030337 0.0247 12.55611 48.45977 174 Source Model Error C Total An*Ws ofVadanco DF Sum ofSquares Mean Square F Raflo 1 848.392 848.392 5.3813 172 27116.827 157.656 Prob>F 173 27965.218 0.0215 Term Intercept PFOS Parameter Estimates Esdmate 51.01971 -1.17509 Std Error 1.457347 0.506557 tFlato 35.01 -2.32 Prob>gl <.0001 0.0215 PolynomiaFlitdogr".2 HOL-Cholesterol 53.5286-3-30537 PFOS + 0.25758 PFOSA 2 Summary ofFit RSquare RSquare Adi 0.053266 0.042193 Root Mean Square Error Mean of Response Observadons (orSum Wgis) 12."3 48.45977 174 Source Model Error C Total Analos ofVadance DF Sum of Squares Mean Square F Rafio 2 1489.605 744.802 4.8105 171 26475.614 154.828 Prob>F 173 27965.218 0.0093 Term intemept PFOS PFOSA2 Parameter Esdmates Esdmate 53.5286 -3.306373 0.257676 SW Error 1.898856 1.160937 0.12657 t Rago 28.19 -2.86 2.04 Prob>ftl -c.0001 0.0060 0.0434 SCattec PLot of HDL and PFOS, Antwerp, L995 HDL-CholosterolBy PFOS 100 90 80 70 60 50 40 302010 0 .00 2.00 4.00 6.00 8.00 10.00 12.00 PFOS 14.00 - Unew Fit - PolynoffdFailtdogree-2 Unew Fit HDL-Chaktgeml - 55.2981- 0.93355PFOS Summary ofFit RSqtjare RSquare Adi Root Mean Square Error Mean d Response observations(orSum Wgts) 0.019736 0.008337 12.32088 53.5 88 Source Mocial Error C Total Analysids Vaftnoo DF Sum of Squares Mean Square F Ratio 1 262.842 262.842 1.7315 86 13055.158 151.804 Prob>F 87 13318.000 0.1917 Term lntemept PFOS Parameter Esdmates Esdmate 55.298149 -0.933553 StclError 1.895379 0.709469 t Ratio 29.18 -1.32 Pmb>ftl <.0001 0.1917 PolynomialFitdogreem2 HDL-Cholosteral - 56-91 - 2.68656 PFOS + 0.24725 PFOSA 2 Summary of Fit RSquare 0.033054 RSquare Adi Root Mean Square Error Mean ofResponse Observatons (orSum Wgts) 0.010302 12.30867 S3.5 88 Source Model Error C Totw AnalysisOf Variance DF Sum of Squares Mean Square F Rato 2 440.212 220.106 1.4528 as 12877.788 151.503 Prob>F 87 13318.000 0.2397 Term inwcqn PFOS PFOS^2 Parametw Esdmates Esdmate 56.910034 -2.686566 0.2472466 Std Error 2.400276 1.768392 0.228508 t Rado 23.62 -1.52 1.08 Prob:,.ftl -c.0001 0.1324 0.2823 Scatter Plot of HOr@and PFos, Decatuc, 1995 100 90 so 70Goso 40- 30 2010- 0.00 HOL-Cholosterol By PFos %%a a 2.00 4.00 6.00 8.00 10-00 12.00 14.00 PFOS Unew Fit - PolynorrJRatldogres-2 Unear Rt HDL-Cholostard - 45.0317- 0.7097 PFOS Summary ofRt RSquare RSquare Adj R ve Error Mean of Roqwnso Obseriadons (orSum Wgts) 0.014998 0.003272 10.8&T" 43.30233 Source Model Error C Total Analysisof Vwfar" DF Sum of Squares Mom Square F Ratio 1 151.843 151.843 1.2790 84 9972.296 118.718 Prob>F 85 10124.140 0.2613 Term Intemept PFOS Parameter Estimates Estimate 45.031672 -0.709695 SW Error 1.928382 0.627527 t Ratio 23.35 -1.13 Pmb>ftl -c.0001 0.2613 PolynomialFrtdogr".2 HDL-Cholostarol - 47.1802 - 2.18908 PFOS Summary of Fit RSquare + 0.16422 PFOSA2 0.028286 RSquare Adi Root Mean Square Error Moan ofResponse Observaflon3 (OfSUM WgtS) 0.004872 10.88702 43.30233 86 Source Model Error C Total AnalysisOf VadanCO OF Sum of Squares Mean Square F Rago 2 266.376 143.188 1.2081 83 9837.764 118.527 Prob>F 85 10124.140 0.3040 Term lnwcw PFOS PFOSA2 Parameter Esdmates Es*nate 47.180201 -2.ISSM 0.1542222 SW Error 2.789208 1.523604 0.1"758 t Ralio 16-92 -1-44 1.07 Prob:..ftl -c.0001 0.1545 0.2898 Scattec Plot of HDL and PFOS, Both Locations Combined, 1997 HOL-CholosterolBy PFOS 100 90 80 70 60 so 9 4 0- %% % 30 20- 10 .00 1.00 2-00 3.00 4.00 S.W 6.00 7.W 8.00 o.w lo.w PFOS 12.00 Unear Rt Po"ridal Rt dogroeq Unew Fit HDL-Chol"orol n 46.3275- 0.45133PFOS Summary ofFit RSquare RSquare Adi Root Mean Square Error Mean d Response Obswvadons (orSum Wgts) 0.004661 -0.00212 10.57408 45.53691 149 Source Model Error C Total Ana"s ofVadance DF Sum ofSquares Mean Square F Rago 1 76.804 76.804 0.6869 147 16436.243 111.811 Prob:PF 148 16513.047 0.4086 Term lntemept PFOS Parameter Esdmates Esdmate 46.327525 -0.451333 Std Error 1.288559 0.544563 t Rago 35.95 -0.83 Prob>@l <.0001 0.4086 PolynardaFlitdogr".2 HOL-Cholosteral- 46.8473-1.03203 PFOS + 0.08884PFOSA 2 Summary ofFit RSquare RSqtjare Adl 0.006173 -0.00744 Root Mean Square Error Mean ofResponse Observaton,s (OfSUM Wgt3) 10.60212 45.53691 149 Source Model Error C Total Analysisof Variance DF Sum of Squares Mean Square F Ratio 2 101.936 so 968 0.4534 146 16411.111 112.'406 Prob>F 148 16613.047 0.6363 Term Intercept PFOS PFOSA2 Parameter Esdmaws Es*nate 46.847332 -1.032032 o.oee84O4 SW Error I.NW67 1.343985 0.187882 t Ratio 27.62 -0.77 0.47 Prob>pl <.0001 0.4438 0.6370 Scattec PLot of HDL and PFOS, Antwecp, 1997 100 go- 80 70- HOL-CholesterolBy PFOS s"o0-9 40 % C3 x 30- 20 10 .00 1.00 2.00 3.00 4.00 5.00 6.00 7.00 8.00 9.0010.00 PFOS 12.00 Unew Rt P*wngal Rt dogme-2 UnewRt HDL-Chole3twd - 50.2864- 0.41131 PFOS Summary of Rt RSquare RSquare Adj Root Mom Square Error Mom ofResponse Cbservation3(orSum Wgts) 0.00232 -0.01352 10.86"2 49.67692 65 Source Model Error C Total An*,sisofVadarce OF Sum ofSquares Mean Square F Ratio 1 17.2928 17.293 0.1465 63 7436.9226 118.046 Prob>F 64 7454.2154 0.7032 Term Intercept PFOS ParameterEstimates Es*noo 50.28CA04 -0.41131 Std Effor 2.086111 1.074642 tRatio 24.11 -0.38 Prob>pl <.0001 0.7032 Po"rrial Frtdogr".2 HOL-Cholosternol52.4254- 4.16781PFOS + 0.90954PFOSA 2 Summary of Fit RSquare RSquare Adj 0.020968 -0.01061 Root Mean Square Error Mean ofResponse Observations (orSum Wgts) 10.84934 49.67692 ss Source Model Error C Total Analysisof Variance DF Sum ofSquares Mean Square F Ratio 2 156.3026 78.151 0.6639 62 7297.9128 1.17.708 Prob>F 64 7454.2154 0.5184 TWM InUmW PFOS PFOSA2 Pwwotor Estimate 52.425357 -4.167812 0.9096417 Estimates SW Etmr 2.865909 3.819458 0.836957 t Rado 18.29 -1.15 1.00 Pmb@-ftl -c.0001 02mg 0.2814 Scattec PLot of HDL and PFOS, Decatuc, 1995 HDL-CholosteroBly PFOS 100 - 90 - 8070- so- % so- rso!f@e: % ,ma =-a a 9 40- % 30-se 20- 10 0 .00 1.00 2.00 3.00 4.00 5.00 6.00 PFOS 8.00 9.00 10.00 12.00 UnewRt P*wfdal Pt dogroo=2 UnewRt HDL-Cholestwd - 42.3281+ 0.00268 PFOS Summary ofFit R@Squwo RSquwo Adj Root Mean Square Error Mean d RoWnse ObsermiJons (orSum Wgts) 2.712o-7 -0.01219 9.293759 42. 84 Souroo Model Error C Total Analysisd Vaftnoo DF Sum of Squares Mean Square F Rado 1 0.0019 0.0019 0.0000 82 7082.6647 86.3740 Prob>P 83 7082.6667 0.9962 Term lntempt PFOS Parameter Esdmates Esdmate 42.328069 0.002685 Std Error 1.508131 0.569385 t Ratio 28.07 0.00 Prob>pl <.0001 0.9962 PolynorNalFitdogres-2 HDL-Cholosterol n 42.5348 - 0.20021 PFOS + 0.02723 PFOSA2 Summary ofFit RSquare 0.000231