Document EKm23xa0Gv1DQy7JKGE1V4oN

ReRseeseaarrcchh Hn TThhee CC88 HHeeaalltthh PPrroojjeecctt:: DDeessiiggnn,, MMeetthhooddss,, aanndd PPaarrttiicciippaannttss K`SSyttleeopphShaatnneiieeonJJl..aFFnrridsibAsenbeoe,oie~p,AA'S..hPPaaanuulkl aBBrrroo2,ookkSssaJrJrar.h.?SA.ArrKtthhnuuorr!MMaCahehecreilr?PPoPalltaastrsydy,F"FlJleeonnuss!bbAoo.rrgag,l?3vSSeuursssaaonnn,AA!rmnVooolrdal,n3iTTcaoonniy.yFFiVleeitteccihhreoarr,4 Chuaniang Jin," Kevin M. Loyden," and Alan Kyle Steenland,a Anoop Shankar, 1~ Sarah S. Chuanfang Jinfl Kevin M. Leyden,7 and Alan M. Ducatman' Knoxfl Cecil Pollard, M. Ducatman~ ~ Joel A. Halverson,~ Ver6nica M. Vieira,a DMR1MDeeedseadiepicacaiprirnnctemeha,,eUMMnrotnoorortgfgfaCLaCnmoonotnmtmoodamwwomunnnnn,u,iSnWWcttiohtyeyossoMtMtleVVedodiiifricgncoiiisnnnleie,a,,a,aaUUnnnSSddAAa:2";CcCB3aeBrnnTrteoroeroocrkpfkoomirarCca.aCrM,raonIrdndedoci..oiu,vsPnPacaesaurckLlrueoalraansrrdbsaaounnnr,gdd;R, ReiUWseneepsisisportiVdraVatiitKorongririyyanSdiS,caoc,oiSUe:nnSccA`Aeep;ssa,`4WPPW rouuiebsbmsiltiatccVnVHiHtireregagaoililfnnttihhimaaUaaUnonndndiinvvEEennrmvsiivrteoyinSSrmcrchnheaonooiotonallooff Research Unit, London School of Hygiene and Tropical Medicine, London, United Kingdom; SDepartment of Environmental and ccupulonat Heat. ReScholofPubl Hest, EmoryUnraty, ALAM. Georgia, SA: DeparmenotfEnvironmental Heal, Occupational Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA; ~Department of Environmental Health, SShionoc!eo,f WPeubslticVHiragsihs.UBnovsatornsyU,nvMeorsrigtayntBoons,onioMsasvsiscdihnuas,aSt,AUSA: epsriment of Pllc sence, Evry Glegsof As nc School of Public Health, Boston University, Boston, Massachusetts, USA; 7Department of Political Science, Eberly College of Arts and Sciences, West Virginia University, Morgantown, West Virginia, USA BAcRGRO0N:The C8 Heh Procwasrtd,shoreda,d edd asptfte ements 7 [periorohepranoic scid (PFHpAL I~*ACKGROUND: "Ihe C8 Health Project was created, authorized, and funded as part of the settlement pt ed nbceoJk Weal. de ondeNoms Corpo, peilscrosomno sed (ENA, CIO agr~ment reached in the case ofJack W. Leach, et a!. v. E.L du Pont de Nemours ~ Comparty (no. Clad Wa aad GyCc Cour,10Ape 2003). Thesmn mm fom [pecuorodecanic cd (PFDA, C11 [per 01-C-608 W.Va., Wood County Circuit Court, filed 10 April 2002). The settlement sterm-ned from heperbarvocinic 34 (FON, C) caminoof dining vac sc war drs Moroundecnoi cd (PFUBAY, and C12 the perfluorooctanoic acid (PFOA, or C8) contamination of drinking water in six water districts in ovenoeDoonWain orksExt ne eb WowV, on. perorndodecdc(aFnDoOk. PFCs ve two states near the DuPont Washington Works facility near Parkersburg~ West Virginia. OnThstud pons on the mths ndesl rodeC8Heth Pfc,pop 154 po wegz ges, n, d cm OI~JECTIVES: "Ibis study reports on the methods and results from the Cg Health Project, a populaey red og dao od hon cb se en FON ots he cof ropes. tion study created to gather data that would agow class members to know their own PFOA le~ls ndperm neq demi vegion ndingproducts tht part onic best and permit subsequent epidemiologic investigations. THOS Fn tadariipaion vo 6903. xed x 15 men peed in 20052006, Fane coneo rete yc vie METHODS: Final study partidpation was 69,030, enrolled over a 13-month period in 2005-2006. Excise colli ling ogra du. ec dae bh leon and rock propre obs. PFmay Cao sul Extensive data ~re collected, including demographic data, medical diagnoses (both self-report and mil oi vio). mk bbarry st snd dermiaton of sr conosions of rom he mecbulno envionment bck medical records review), din:ca: laboratory testing0 and determination of setutu concentrations of 0 pecrnarbon (PFC. Herwedecree poonedrtcolt wld and woe hse dof fried cocinchingcers. 10 perfluorocarbans (PFCs). Here we describe the processes used to collect, validate, and store these ok da Weidocrbemiryputt i a crvmPEC ed 0cost commeord packing. health data. We also describe survey participants and their serum PFC levels. Rist The opaluin mc manforsr PFON as 3291 mn, S05 igh dun 3 ri bu esrfo isand RESULTS: The popuhtion geometric mean for serum PFOA ~s 32.91 ng/mL 500% higher than prowl etme for + eecAincoapotpulioin.Seen coeembtiperodorne: cting PFOA may hobe skal inary previously reported for a representative Atuerican population. Serum concentrations for perfluoroee whitead rethareemaeet a0 wee Seid 7% 2207 coped miss Imac roe. hexane sulfonate and perfluorononanoic acid were elevated 39% and 73% respectively, whereas Peasant Jv st ho 1 USpopin: CeKuti FEO and ther PECs perfluoronctanesulfonate ~s present at levels similar to those in the U.S. population. ConcThiuarsg koonrpso:inofctrmmunyity PFC capo peri newcl pei in he circ 0d 4c ound in CONCLUSIONS: Tnis largest known population study ofcotumunity PFC ~posure permits new evalu~ cnof snaciions weesPEONin pac, nd onof gkbar. Ths icon. eoundwate and sarc wares worldwide ations ofassociations between PFOA, in particular, and a range ofhealth parameters. "Ihese ~4]1 conrteui dm ofteol fPEC spr. The Ck Pc sosep on (hit a1. 2008). They are present tribute to understanding of the biology" of PFC exposure. The C8 Health Project also represents an npn iegrbu deoan yr Fou drone ao sion be nd et onto rl unprecedented effort to gather basic data on an exposed population; its achievements and llmltatinns et Le Sanda] ee Ste Si] spon can inform future legal settlements for populations exposed to environmental contan,inants. ons Ci a Sr ON pair Sol a KEY WORDS: C8, environmental contamination, perfluorocarbons, PFOA, toxic tort settlement. Euro Hh Pops 171373 T852 G009). of10.1851 OSS vile wis Bens seed and mmmocd te Environ Health Perspect 117:1873-1882 (2009). doi:10.1289/ehp.0800379 available via ht~p.'// LOe ne 133 200] Known woxclogi properties, nono dx.doi.o~g/[Online 13 July 2009] Perluorooctanoarc acid (PFOA. or C8) [peoroocunose (PFO). A cy rbd deistebu0ionP,FO2A2d(Kpeennneadylthoe.at2h04c;oncKeordnos. Perfluorooctanoatic acid (PFOA, or C8) is one member of the ls of manmade PFC b perlaoroocancilonse (PFOS: C8 1d Kwabin 200% Lact 007). Ail is one member of the class of man-made pefluorocrbon (PFC) compan. PFOA slfnsc, or CB. Additonal. ened PFCs oncology dishav ggoredpci up- perfluorocarbon (PFC) compounds. PFOA ies 232m aly acd (PFOR), 30 ammo: inde C3 pecluampenolc xd (PFPA). preowfiuornl muni, neroedocine exists as an alkyl acid (PFOA), an atumoium sale [ammonium peruoroccianowe G6 pefombecna i (FHA Col. cic, and expose ened otaons nd nium salt [ammonium perfluorooctanoate ATF), ov dicted conjoos bse ons [prtanrobsane lone (PFHSY, developmen fo. Comin evidence (APFO)], or as a dissociated conjugate base [perfluorooctanoate (PFO)]. A closely related PFC is perfluorooctanesulfonate (PFOS; C8 sulfonate, or C8S). Additional, rehted PFCs include C5 [perfluoropentanoic acid (PFPeA)], C6 [perfluorohexanoic acid (PFHxA)], C6 sulfonate [perfluorohexane sulfonate (PFHS)], C7 [perfluoroheptanoic acid (PFHpA)], C9 [perfluorononanoic acid (PFNA)], C10 [perfluorodecanoic acid (PFDA)], C11 [perfluoroundecanoic acid (PFUnA)], and C12 [perfluorododecanoic add (PFDoA)]. PFCs are reed as plasticizers, wetting agents, and emulsitiers during the manufacture of fluoropolymers~ induding products that impart nonstick heat resistance to cookware or breathable yet waterproof properties to fabrics. PFCs may also result from the metabolism or e~wironmental breakdown of fluorinated telomers, hacluding chen'ficals used to coat commercial food packaging and for stain-resistant treatment for fabrics and clothing. PFOA may also be a residual impurity in personal care products. PFCs and health. PFOA and other PFCs persist in the environment and are found in groundwater and surface water worldwide (Yarnashita et al. 2008). They are present in blood and other tissues of animal species throughout the world, including remote regions (Tao et al. 2006). Recent publications have extensively reviewed and summarized the kaaown toxicologic properties, environmental distribution, and potential health concerns related to PFOA (Kennedy et al. 2004; Kudo and Kawashima 2003; Lau et al. 2007). Anitual toxicology studies have suggested potential suppression of humoral inununity, neuroendocrine effects, and exposure-rehted gestational and developmental effects. Cumulative evidence i mS] oe or Ves eySeto one Rober Be Fh SomeGrr, Web Coe FO B15, Address correspondence to S.J. Frisbee, West Virginia Universirr School of Medicine Robert C. Byrd Health Sciences Center, I Medical Center Dr., P.O. Box 9105, Niro WA36509103 SK. Tabor (O) 954553 Fx Os 933515. ecg vio Morgantown, WV 26506-9105 USA. Telephone: (304) 293-6552. Fax: (304) 293-5513. E-mail: sfrisbee@hsc.wvu.edu mcd Na bbe nt h 10.585 ApS) ah Supplemental Material is available online (doh 10.1289/ehp.0800379.S 1 v~a hrrp :/Mx.doi,org/). ve mole he coco of. Yourg 1 R. Wh (CTR Sh Grp) fo poring nfm ios he recs We gratefully acknowledge the contributions of T. Young and R. Whitener (CPR Solutions Group) for providing information teclmology solutions to the project; Lad (ry Coe RoloSelo ti Hkor hrcet ano alain pene Engen Rech Coorg C. Latiy and J. MacNeil (Emory Universi,ty Rollins School of Public Health) for their expertise and assistance in data cleaning; personnel at Ex~vgen Research Corporation A Ao gamedco ry hobo 4m rb erat de Conf aon.Ve he pron and g-x.vs Aaal~ics for ensuring accurate descriptions of hborato,ry methods; and D. S avitz for his assis~anoe during the preparation of the manuscript. We also appreciate oonof coe Fo: he ef C3 Hh rope ct tm dorimei ee dt depsto the suggestions of reviewers. Finally, the scale of the C8 Health Project neoessitated that many individuals provide valuable assistance during its development and imple- egyino ctom nk stb patel ts cto ofp.The tes fe a he men,anon. We gratefully acknowledge these contributions and thank alI those individuals who supported the execution of the project. The entirety of the funding for the ai en st rat be elm i cf Leh EL Poe Nr8. G1 re 0. 09 350 Fai C8 Health Project was achieved pursuant to the settlement agreement in the case of Leach v. E.Z du Pont deNemours & Co. (civil action 01-C-608) in 2004. Funding ~vas Sitasurn cet peed eb pet administered by a named, court-approved health project administrator. SIRS, SIC. TATE CJ. KVL odAMD,met rp i eprec put 3oeeinem rks, fc. nd WesVia S.J.F., A.S., S,S.K., C.P., JA.H., C.J., ICM.L., and A.M.D. were engaged in the project pursuant to a contractual rehtiouship between Brcokmat, Inc., and West Vi~nia Ue on atorp ome oemt se ed th University. These authors have no oarrent or prior competing financhl or nonfinancial interests to disc!ose, and declare that their ab l~ty to des~n, conduct, interpret, or publish chi~ research was unimpeded and icai~y independent of the court andlor ~xding parties. As described in the art~e~ Brooknaar, Inc. ~ a for-profit company created sote[y to carry oC Heh Pepto dts es oe oe thot eof od le eoll LodNL out the C8 Health Project component of the court-directed settlensent and remained an active entity throughout ~e course of and ant[[ the dosare ofthis study. A.P.B. and A.M. ome Jo Moi SA et shang ie were the sole owners of Brookmar, Inc., and P.F. and S.A. mere its employees. Brookmar, Inc. received ftmding exclusively from the settlement, administered through the health Foesims ht etAdd eae ero oe i bed elton i, i A dbo AE project adm~swator, to conduct the project. As described in the artHe, the design of the project was devebped ha consultation with, but not subjec~ to, tbe wishes of the settling FB AR TAFE deft Sy rs A mor i By apt ect de ing parties. However, A.P.B., A.M., P.F., and SA. declare that their ab~ity to interpret, and publish this research was unimpeded and fully independent of the coort and/or se~ing parties. T.F., K_S., and V.M.V. are members or contractors of the court-approved C8 Science Panel. As such, they received funding from the C8 dam action settlement agreenxent EcDui mdphn eg bofvipefoin cd rinws, hichwesod he CirceCor Ro ony, Wt between DuPont and plaintiffs resuking from releases of cher0dcal perfluorooctanoic acid into dr~ water, whi& was approved by the Circuit Court ofWood County, West Vio. Tokando o htd sboes. oc,i PA chvasl dK pf cr do ogFo Virginia. Tiaese authors declare that thek abili9, to design, conduct, interpret, or publrsh research was unLmpeded and Nliy independent of" the cotirt and]or setdrag parties. In i, ime tempmoer addition, they declare no nonfinandai competing interests. Reon No30e0:xspd1310820, -- Received 8 November 2008; accepted 13 July 2009. f Exhibit ~ Erion Heth espectves -ve 117 wae121 Dente203 swamr2m7a1n3nes, | 1673 Envlronm~,al H~alth I'~'sp~.tlve, V~LU~E 117 I .UUS~. 12 I De~ernber 2009 :~~~ ~:~on,e;7~aVv.;;.~8~ 1873 22771133..00000011 Bn Fitee tal. Frisbee et al. om aman rl sesbs oggosed Orofisheg8iHnl rjc. The (Gi 0.1289chp 08003795] becween from mammalian animal studies has suggested from mngimtog EN Segtl piJ AE Ry that the liver is an important target organ. Report poTmos elenoes Sie atb ao lg Eid | Tox molbemd aerdbgnedStT Reported hepatotoxic effects include liver corn palmimoma ani 30s As Gand vos sy fom of espe bat Se ted oe tha enlargement, hepatocellular adenomas, and periplc pel prods (1. du ToedeNemo&uCor)sin 1984 weve sted.Pot ho ngiaions oxisome proliferation [specifically peroxisome kon acim pr TEAR)po. whch bq comahenbad ae ewe slingpris stl ho te proliferator-activated receptor (PPAR)-e~], posSi es emo So i he do of wi ro on bth nd sho eaandCl sibly suggesting a possible nongenotoxic carciops PFC TEC manta fo th Wahingion eh mobue lhidnd roth a pol nogenic mechanism for PFCs. dona. comin sido pons Wars pla. The funy alge ha doe fon wide kts uy of he Cis: lly Additionally, combined evidence supports at TFC. emt, and PFO and FES ihn anon) chemi om the and Known 2s the "Sqn Clase 1th & that PFCs generally, and PFOA and PFOS pelle pp nhnode Bl spo ot aly ri wid, Ei rf 2nd acth C5 Hes specifically, are present in the sera of diverse rn polLoa s8.007 Int edo ad he de of as 300ed Poeoerte.n eprom. human populations (Lau et al. 2007). In the EP Fi. United States, almost all National Health and Noviion Eamon Soy (NANES) Note 1 (do10.1 3891p 080037381 vfs ii and pl she Fos om Nutrition Examination Survey (NHANES) Simple conned hee chico, with bpdHbror). Th Bm aged to 3 our serio. Thre splomiologis samples contained these chemicals, with SO apultion medionof 3 py FRO cobalt with Donn 2001 the C3 Scknee Fane) weg ppc a U.S. population median of 5 ppb PFOA. Th PEON and ROS omencaions ws asc ol acini. inccing indepen. dine the presen. shoof hi Both PFOA and PFOS concentrations were ht in he rum ofmem nd short wil rl compared ds and gor Bd th co re ob Bo. ben higher in the serum of men and those with her doin (Cll2 007 JOT). by torment spencis sed to proidt PFO pest an human discs ee higher education (Calafat et al. 2007a, 2007b). Ahhpcs snes of man po cn vonmenl ds and high Toca SppMaica,nNotc3 (Gnorl. Although potential sources ofhuman exposure Cobmsvoiet Gara, os ova of he xpos nA il on Sp 0R00379.S1. radio 1 Frfck continue to be investigated, current, known ros of PRON coe foal incl ng or rete i th C3 Scene Poe nce do sources of PFOA exposure generally include inking tc, houkheld don, nd ooo The allowing poi summarikzeey iv, risescommuni si drinking water, household dust, and food or igi fom fodpadoging Gn arid, vcs in the amo oow cd mee pronod cpondoen migration from food packaging (in particular, Corraalnd Eo oho package in oCBh Hkh rt resSn pe lem commerdal and fast-food/take-out packages) nce at, 00, Octal Cocm itn i dev tPRONecn: ondln degCouto pop and cookware (Lau et al. 2007). Occupational i oe Shown devilwider coun tamaifwnatiSUPtP iloon dnhe onSpota ap ii isn wll studies have shown devated worker exposures Bn manucuting pocsuts hat to TEOA mi-Ohio Kiva Valle approsimacly shofpeeesr eh Thyscote in manufacturing processes that use PFOA 1 TEGS (Emm a 3006, Gon ca, 1904-2000 Wits pollwais tnhg. commis pre, 00s pnpws or PFOS (Emmett et al. 2006; Olsen et al. Soo wed vo dict dopa memes fom the sable sot or Clos hrs 0 2003). Human popiaion sucicspredomimny Dafon's Wshigion Wors lant into bench fom she men, bt nes Ch Human population studies, predominantly Ut mp A Lp i A ed ep medical surveillance studies of male American atopachorpat0oOnlwy edag r ni d nbanplgan Heri. sok. rr Po workers exposed occupationally to PFOA or TRON, he pond meoniven ndings mar broadly omtaminicd erbl abr 5 somonloy hdl Waok PFOS, have reported inconsistent findings (ona 07) bo otre is rm. hh ht an. 3sCo mesno egz i (Lau et al. 2007). Although some studies have aroiet Dnoa aki on ont Tr rt To go reported associations between exposure and ee ladder and ros onda, ring wet sou 0.3 orl oi ob. deer hon sie) ped cancer (bladder and prostate in particular), Tk, le comes,adsome dprld bor. iy Tk Suplemenal Marr, Now3 comuniy appehnion xrosed eid lipids, liver enzymes, and some thyroid horans oll iis and ope hove 10.1289 RST) Sn mon te mones, follow-up studies and others have Gir canadien ins o found + Angst 201 though Apr 2002: Thien sts on iby ad ven employ. either contradicted earlier findings or found idence sggening eplnaion hiouth ims Fld Hk api Dabo 1. and the dis orprirscv evidence suggesting explanation through Colon params (Lan oo 3009. which was bagi coh a cos psonalzed oration how abo confounding parameters (Lau et al. 2007). Staten ered eo Al tare ol We Sout Lt Iv gt ote Soot Poli ht. Taes Maternal serum and neonatal cord blood studhas mplcnad im suiadof oFOnN Noms Co (Col Action No, O1.C. ndings.Tog dota sllcion method) ies have implicated an association of PFOA PROS wh bh wath (Marg co. G09, ed nthe WoodCounty We implencotbey ToIkn oate,d or PFOS with birth weight (Apelberg et al. S507,Wa309i btsel sso VinicgCo.un. TheCuswas ilyorci bycofomr ees. 2007; Washino et al. 2009), but there are also yng cy op. nt id, Ve Via Ungar, hho io. contradictory findings in high-exposure popudan (No a oF, 2008, The MATTE of Obl,whediking was hd bn con lations (Nolan et al. 2008). The half-life of BEGS and PEON in umn sr has been aniby aounf loflPFOA. CB Health Project Methods. PFOS and PFOA in human sera has been epoch as approsaindm3.a5 yleya. + November S00: A mabicompaSn07e Elgbli. Cl aig wa dened by reported as approximately 5 and 3.5 years, eee Glens 307) hon pl sedemens ee th. nt Somamied wae. respectively (Olsen et al. 2007). Salarrt rl il; Cos and Bobo wi rnd Comte oh Pepi apata In a review process that remains ongoing, 1h US Tovimmen TonecionAgcy sepent wm ve on of he plc nd xponne guston.Ky bets dl the U.S. Environmental Protection Agency FE ring SRnS ALY lle hn e a hn ndg (EPA) is considering evidence and classificaa of PRON a ily hom canon ne 370 Allon ward for Clos mem: 5 pe vcs dos on Wot Vim tion of PFOA as a likely human cardnogen (USTED 2006 The U's. EPs PFOA bes ofwhichS30 millon wsrived volo in Ohl ss Spleen Moca (U.S. EPA 2006). The U.S. EPA's PFOA Sicuaribi Togram prosries PFOA be wadfor eh andshoproocs, Bre 1 110i.p100D28SD)5or Stewardship Program proscribes PFOA, FFON poi ves HE ms: Prote ofght riot wdmologis hom rt wht ae wb te Bo PFOA precursors, and related, higher homoer oe ainies septs tor PEONfom thevot ply opin rnta segue logue chemicals from emissions and products S015 15: EFA 2009: Tn th ropa of he acid ws itis ami. Whecoma 0.n05pdlPOR nd) by 2015 (U.S. EPA 2009). In the European Cron, toe st af PROS and dais ado of an rein pre of dh aywd 2 wren 3 mondo Union, the use of PFOS and derivatives td i 2000 dba TOUS, a Spee oy ov 3 TRY Spgs oo watebt e 0 was stopped in 2000 and banned in 2008, hou TRONwe romin ply an say and doi ob 3 prob Dore 2003 pry dee, although PFOA use remains largely unreguTe Gnen and Leto 300) nk? Toe Sopplemenal Mate Noe 3. cof opiofbns lated (Jensen and Leffers 2008). Origin of the C8 Health Project. The C8 Health Project can be traced to legal actions taken by a local family. A portion of this family's farmland was sold to DuPont (E.I. du Pont de Nemours & Co.) in 1984, which subsequently converted the land parcel into a site to dispose of waste products from PFC manufacturing from their Washington Works plant. The family alleged that the (then unknown) chemicals from the landfill were responsible for family illness, wildlife death, and the death of almost 300 head of their cattle [see Supplemental Material, Note 1 (doi:10.1289/ehp.0800379.S1 via http://dx.doi.org)]. The family agreed to a confidential settlement with DuPont in 2001; associated legal activities, including independently commissioned studies and reports filed by government agencies, served to provide environmental data and to heighten local awareness of the exposure, coincident with an emerging scientific literature. The following points summarize key events in the almost two-decade time line leading to the C8 Health Project: Cumulative evidence detected PFOA con- tamination of water supplies along the mid-Ohio River Valley (approximately 1984-2004). Water pollution was attributed to direct industrial releases from DuPont's Washington Works plant into the Ohio River, a prindpal source of public drinking water, and airborne pollution more broadly contaminated water tables and aquifer systems, with subsequent contamination of well water, an important drinking water source in a rural community [see Supplemental Material, Note 2 (doi: 10.12891ehp.0800379.S 1)]. August 2001 through April 2002: Thirteen plaintiffs filed a lawsuit against DuPont, which was subsequently certified as a class action, Jack W. Leach v. E.I. du Pont de Nemours & Co. (Civil Action No. 01-C608), filed in the Wood County, West Virginia, Circuit Court. The "Class" was defined as individuals, in West Virginia or Ohio, whose drinking water had been contaminated by quantifiable levels of PFOA. November 2004: A multicomponent $107 million pretrial settlement between the Class and DuPont was reached. Complete settlement terms are part of the public record. Key provisions included the following: a $70 million award for Class members, of which $20 million was required to be used for health and education projects; provision of water treatment technologies to remove PFOA from the water supply of the six affected water districts; and formation of an independent panel of three scientific experts to carry out a community study and determine if there is a "probable link" [see Supplemental Material, Note 3 (doi: 10.1289/ehp.0800379.S 1)] between PFOA exposure and human disease. The settlement broadly outlined terms of agreement but did not detail how they were to be satisfied. Post hoc negotiations between settling parties resolved that the health and education projects and Class payments would be achieved through a population-wide health study of the Class, initially known as the "Settlement Class Health & Education Project" and later the "C8 Health Project" (the Project). An independent company, Brookmar, Inc., was created to design, publicize, and implement the Project under court supervision. Three epidemiologists (the C8 Science Panel) were appointed to determine the presence or absence of what the court termed a "probable link" between PFOA exposure and human disease [see Supplemental Material, Note 3 (doi: 10.12891 ehp.0800379.S1)]. In addition to Project data, the C8 Sdence Panel is to indude data de novo, prospective community studies that they proposed and are conducting. The Project faced significant implementation challenges, induding Court and population expectations for rapid time lines as well as absence of precedent for the likely scale of the community project. Project partidpation was the established route for Class members to benefit from the settlement, but neither Class size nor participation was known a priori. Accordingly, Brookmar, Inc. developed procedures to accommodate rurality, shift workers, eligible Class members no longer living in the area, a wide range in partidpant age and mobility, a deliberately short survey period, community apprehension expressed regarding data privacy and concern about adverse effects on insurability and even employability, and the desire for participants to receive personalized information about laboratory results and general information about Project findings. The data collection methodology implemented by Brookmar, Inc., agreed to implidtly or explidtly by counsel for the setding parties, is described below. C8 Health Project Methods Eligibility. Class eligibility was defined by exposure to contaminated water, a combination of geographic and concentration criteria, and exposure duration. Key criteria included a) exposure to contaminated water from any of sLx public water districts [two in West Virginia, four in Ohio; see Supplemental Material, Figure 1 (doi:l 0.12891ehp.0800379.S 1)] or from private water sources within the geographical boundaries of the public water sources which contained > 0.05 ppb PFOA, and b) the ability to document a minimum 12 months of ~xposure to contaminated water between 1950 and 3 December 2004, at primary residence, place of employment, or school. 674 So 17 at12 December 209 EnHeo hPpns 1874 VOLUME 117 I NUMBER 12 I December 2009 . Environmental Health Perspectives 22771133..00000022 CC88 Hlth Health PPrroojjeecctt mmeetthhooddss aanndd rreessuullttss Hn Panicipans supplied documentation. for survey da, inching. quo or do accodancs wich the credo sands Participants supplied documentation demomsratng both di Key and expo dophons cay ot papermadore nd pif aboson demonstrating both their identity and expo"ur wing combination of Courtdeine clectraicband logic role (cg, mcd Th primary Bborsory performing PFC sure using a combination of Court-defined Kipabl documents, rooknarn,c nde noes men) for Whst avy,ere anal Eyes Resch nsSateCols, acceptable documents. Brookmar, Inc. independed vere th awhof doc acto dehes ney. PA. USA) vi sce bs on billy pendently verified the authentidty of docuns wih he sing agency, and ley Data solltion procedures. Temporary meet US. Food and Drug Adminission ments with the issuing agency, and identity cumminvasComino curs ts dlroc wks es tabbed th ach dinamol vada, documentation was examined to ensure that iva erecnr n onlyonce, Scam water dtc, sed with nuns, pict 3lowe hi of quantifoifc0atnigo.n partidpants were enrolled only once. Scanned Socuricn copies became pan ofsh pai mis. and ike personne, and equipped 3nd 36-el pli-based tcchology allow document copies became part of the particions Pj secodntcod or venipuncuue, blood processing. and ing for hinoughpus capability. This wax pant's Project electronic data record. "htsepa Footypeofdcwer shoecm record 4nd bac sample ra, as he babyofrondo preioly Data components. Four types of data were colle hab suey lf poned amb Pariepants coud schedle apponamenes reported, indepondendy perfor study collected: a health survey, self-reported anthroome merHoood mnpl,a,nds bavee 0730 3nd 1930 ous 3 dh locon of dnt in ane war dict included pometric measurements, a blood sample, and a lh vontan oud le oFshe meine, Bocasofbh Fb. 11h Projet (mt 31 300), The medical chart review to validate sdected sdf-repond dune. In niin nil bors. vy snd parciant consemions, ing vis PFOA aniicaion and validaon mth: ported diagnoses. In identifying clinical laboraKoryo nd hci dgnosforliion, o redfr pchomy skh. dogwd by tis bornbibp tory tests and sdecting diagnoses for validation, pry vas ge hss with pci a. pried duro vas collec ts line viously dead (Fabry ta. 2005. The priority was given to those with potential assoSo wh PRC poms a pois herreaof Bhs ris. Sn protocol sefo sh Pfc wat 3 dations with PFC ~xposure as reported in the Scenic rors, Clic boston ss At in-person appoimns,pricipans msfcadonof his methodology. Bric, sdentific literature. Clinical laboratory tests inodyes, mma, nd fs submited SRY documencaion andthe the technic ied 3 pci prepiadon included serum lipid, immune, and inflammaory mr ve, doy, adty fone. wes dct nic by the cute doc. curso doit wihrvs pase ih: tory markers; liver, kidney, and thyroid funcors comple Hoo coun scum deco omarion provided as corded; this was perormance id romaogaphy nde tion; complete blood count; serum dectrolytes and prvi and endocrine function, nc. usta but. or says te soneof great ass spectrometry. Spectrometric decction and protein; and endocrine function, includ8 li and Hats Fie upland Spot rs all io ACNE wt Polo ple adel is ing insulin and glucose [see Supplemental NicNoe 4 do 0.1289chp800379. dt, crc eden foraandc,om. Spechromete in secs econ mori Material, Note 4 (doi:10.1289/ehp.0800379. SD) Valdted modal diagnses inca pletionof the hs survey and sk par. ing mods, mani for the did mi S1)]. Validated medical diagnoses included ar dic, cnc, dy dhe, nto: pans pore hk ur hk, ek, dons for xh oufh 10 PECs andthe heart disease, cancers, thyroid disease, neurologan, io snd ts c Sn blood ste, Paria somal C.PFON surge, Rel br the 0 PFCs logic disorders, inflammatory and autoimmune dhrdes, and pregnancy complicuons ce bmibondpe messes vere mearpomed i the Pot disorders, and pregnancy complications [see Soplcncrl Nc, Not Gat 10.1289 Exch ved prican hed $15 for formation se throughsWindowsbd Supplemental Material, Note 5 (doi: 10.12891 p00. comping behave nanabo program (Solemn Mea, Now ehp.0800379.S1)]. "The hesih icy gthred demographic S350 for probvloiod npgle (eg (do 01289/chp080037951). The health survey gathered demographic da curse and Hire reside and of spe quant or quali. Te pryment PRC alyanurans. A co-ed qk data; current and historic residential and Coployment information, nding ver mount ced the ompeneion mcs iy rsa progam wi mplemntad con employment information, including water Sori and was pana moti dines, ohsxe andremanraorrdons Singof ) asoo fwat reablky in source and use; personal medical diagnoses, rumen ining micas, and phys. pakigadon pac. i pray i Gnas rcbil with dhe treatments including medications, and physioF sympoms amily modi hon pr. Blo sample proccng and labora: seof Bark samples, spe spiked vith 3 cal symptoms; family medical history; pregTaney sory nd prams ovcns tory method Wood samplers ob known PRC conten, a paniipant nancy history and pregnancy-related outcomes or women; and oration about Bisyle and processed a dividual do collcon duplicate mpi, ad ) ke of 3 scorn for women; and information about lifestyle and seh txiors, Panicipanes ao lf. ics: Samples were dew inc four tabs cual horny (AXYS Anica Seni and health behaviors. Participants also self"epoch own hight, wih, and blood per participant wih a mau 35 ml for Lud, Sidney, BC, Canada) t deeming reported their own height, weight, and blood sire. Bookman, nc. Somes wih duke and 20. fo chien, Tubes vere PEC concenations for pariipand opie pressure. Brookmar, Inc. contracted with a Sune compatno independ plo ek pun, aliquid, and reigned une sip samples (mica lab. Thi abort separate company to independendy pilot test isacy, anid ronsweemade ed on png. For mii-vlume Grp Seurtts wih the abil 0 monitor 10 individ the survey, and revisions were made based on photos ndings The Bt eimaohfe sr. Sige with prio for PRC ana, PRC and lowe iiof quando of pilot-test findings. The final version ofthe surey was acceptedby th sling paris The Sample were shipped on dy cc dy fom 0.2 ng/mL employed analyte methods re vey was accepted by the settling parties. The mer a lt of te linc bry cst, cach doa colon se the aborsary vious deed (Geni 3. 20045 survey, a list of the clinical laboratory tests, de 15 modi dgoocs vedi by med. etain t meant scum PFC. The cima Tay ta. 2005). Bry. th echique and the 18 medical diagnoses verified by med{cl record view se publicly avalibc on boro comrace perform dh incl sdsold phse cxacion on 3 ws rion ical record review are publically available on Th Ci Heth rjck WVU Da Horn. chery anys pk vp samples dy change colon folloe revere phe The C8 Health Project WVU Data Hosting Webs C5 Hols Proc200) rom cachdocolton st. Addionalh, high-performance iid chomography Website (C8 Health Project 2009). Eri do sat Sn of un om Oh arnt pn Snr: doco Enrollment. An independent information chology (1) company was contac wa Fo 31d subscgucny wored ws pool wig il dpe as technology (IT) company was contracted to Suid ang manage ois sons that Project doe bk ms ed cn og build and manage informatics solutions that addsCo arty concer and coneda Cli Bboy cts wer pom 3c hd, monkoring india ls rion addressed Class security concerns and created a chacd sharin for rjc region ng, independent, acrid Gil di. fo cach ofte ages PEC he UC PFOR, web-based mechanism for Project registration nd hs suey completion. Paiipanes not borvory (1sbCor, Inc, Buigon, 1 C.PFOSn,d | C.PEDA samogcs andi and health survey completion. Participants Cod Samad rece n peso and NC, USA) A cuomied eh let7 mir. 'C PFOA 4nd FOUEA (C5perro 2. could alternatively register in person and use oped surveys. Ar regain and oe ens immedi, ont boron. doi cd) ramen relsande. paper-based surveys. After registration and Complion of he heh su, pains spec cio ours and uh abs Toass mth perfomance the pe completion of the health survey, participants eid imsmcons regarding repens and permed subsequent cron ans. mary bors, lvy control sample in received instructions regarding requirements for demonsraing dil and main an urof circa sorry sal dry nthe oroftmno cml cum bk, tn for demonstrating eligibility and making an "ppeinmen: a Pos drcollcion s. he Proje data sy Chr Iborary ont spikes in con su, and ov appointment at a Project data-collection site. Smad doa iysurance ohio sand dy Sana wis Promed le ophits wr ckuf wih ch bah Standard data quality-assurance techniques for survey data, including a quota for data duplicate entry for paper-based surveys and electronic-based logic rules (e.g., limitedanswer menus) for Web-based surveys, were in place for the health survey. Data collection procedures. Temporary modular office units were established in each water district, staffed with nurses, phlebotomists, and intake personnel, and equipped for venipuncture, blood processing, and short-term record and blood sample storage. Participants could schedule appointments between 0730 and 1930 hours at the location of their convenience. Because of both feasibility and partidpant considerations, fasting was not required for phlebotomy, although sdf-reported fast duration was collected to facilitate interpretation of laboratory results. At in-person appointments, participants submitted eligibility documentation and the water district indicated by the exposure documentation provided was recorded; this was usually but not always the source of greatest exposure. Project staff verified demographic data, current residential information, and completion of the health survey and asked parddpants to report thdr current hdght, weight, and blood pressure. Participants voluntarily submitted a blood sample. Each verified participant received $150 for completing the health survey and an additional $250 for providing a blood sample (regardless of sample quantity or quality). The payment amount reflected the compensation intentions of the settlement and remuneration for Project partidpation expenses. Blood sample processing and laboratory methods. Blood samples were obtained and processed at individual data collection sites. Samples were drawn into four tubes per partidpant, with a maximum 35 mL for adults and 26 mL for children. Tubes were spun, aliquotted, and refrigerated until shipping. For limited-volume samples, serum was aliquotted with priority for PFC analysis. Samples were shipped on dry ice daily from each data collection site to the laboratory retained to measure serum PFCs. The clinical laboratory contracted to perform the dinical chemistry analysis picked up samples daily from each data-collection site. Additionally, an aliquot of serum from each participant was frozen and subsequently stored in a Project tissue bank. Clinical laboratory tests were performed at a large, independent, accredited clinical diagnostic laboratory (LabCorp, Inc., Burlington, NC, USA). A customized health level 7 interface generated immediate, on-site laboratoryspecific identification numbers and tube labels and permitted subsequent electronic transfer of dinical laboratory results directly into the Project data system. Clinical laboratory tests and quality assurance were performed in accordance with the accreditation standards required of this laboratory. The primary laboratory performing PFC analysis (Exygen Research Inc., State College, PA, USA) was selected based on its ability to meet U.S. Food and Drug Administration guidelines for bioanalytical method validation, a lower limit of quantification of 0.5 ng/mL, and 96-well-plate-based technology allowing for high-throughput capability. This was also the laboratory of record for a previously reported, independently performed study of residents in one water district included in the Project (Emmett et al. 2006). The PFOA quantification and validation methodology used by this laboratory has been previously detailed (Flaherty et al. 2005). The analytic protocol used for the Project was a modification of this methodology. Briefly, the technique used a protein precipitation extraction together with reverse-phase highperformance liquid chromatography/tandem mass spectrometry. Spectrometric detection was performed using a triple quadrupole mass spectrometer in selected reaction monitoring mode, monitoring for the individual m/g transitions for each of the 10 PFCs and the I3C-PFOA surrogate. Results for the 10 PFCs measured were incorporated into the Project information system through a Windows-based program [see Supplemental Material, Note 6 (doi: 10.12891ehp.0800379.S 1)]. PFC quali{y assurance. A two-tiered quality assurance program was implemented consisting of a) evaluation of test reliability in the primary lab (intralab reliability) with the use of blank samples, samples spiked with a known PFC concentration, and participant duplicate samples, and b) use of a second, external laboratory (AXYS Analytical Services Ltd., Sidney, BC, Canada) to determine PFC concentrations for participant duplicate samples (interlab reliability). This laboratory, with the ability to monitor 10 individual PFCs and a lower limit of quantification of 0.2 ng/mL, employed analytic methods previously described (Kuldenyik et al. 2004; Taniyasu et al. 2005). Briefly, the technique used solid-phase extraction on a weak anionexchange column followed by reverse-phase high-performance liquid chromatography/ mass spectrometry. Spectrometric detection was performed using a triple quadrupole mass spectrometer in selected reaction monitoring mode, monitoring individual m/z transitions for each of the target PFCs, the 13C-PFOA, ~3C-PFOS, and ~3C-PFDA surrogates and the 13 C-PFOA and FOUEA ( 13- C-2H-perfluoro-2-decenoic acid) instrument internal standards. To assess method performance at the primary laboratory, quality control samples in the form of two control serum blanks, two lab control spikes in control serum, and two sample duplicates were included with each batch comsthe Rpecr ihes + sue 17 a 2/Oc 250 1875 Environmental Health Perspectives VOLUME 117 I NUMBER 12 I December 2009 2713.0003 2713.0003 1875 Bn Frisbee etal. Frisbee et al. of 90 samples analy, UC-PFOA Gro. of 90 samples analyzed. I3C-PFOA (surro50) wasssadel 0 very sme bor gate) was also added to every sample before Surscion asca pearaion. Blkcon extraction to assess lab preparation. Bulk conel lank and sis wie prepared the trol blanks and spikes were prepared at the rimry Ib and Sn o che sampling sc. primary lab and sent to the sampling sites. ey wee then blindly returned with evry They were then blindly returned with every iment of np rp oissr. shipment of samples for analysis to assess stor5 eampor, and iborsoy prparadon. age, transport, and laboratory preparation ic. Fo hs quay contol ples, dh effects. For these quality control samples, the Project IT aye gencraad inne domy Project IT system generated indine dummy idenicion numbers and ow5os fi. identification numbers and two sets of labfeaa rcade phichosomy be bv. Ske ready, bar-coded phlebotomy tube labds. Site ass sliquoted two ssofsample bes nurses aliquotted two sets of sample tubes, nd wer incadod prof sand and both were included as part of the standard Hipment ote piy lborsory Buon shipment to the primary laboratory. Based on + dh clcion tc spc sampling pan, a data collection site-specific sampling plan, `amples wee abo suomtaly Heniid by samples were also automatically identified by he ProjeT system for the secondary ib. the Project IT system for the secondary lab. Libs and cubes wre gered slay, Labels and tubes were generated similarly, as wre sample alguns. Ress fom qual were sample aliquots. Results from quality rane sample were segregated from th assurance samples were segregated from the in, paricpan dss pox hbo y the [1 main, partidpant database post hoc by the IT Company, heoly a, blinded 0 cn company, the only group unblinded to idencation br tification numbering. wing aisof quality ssn During analysis of quality assurance el, commen eesbetwendh pi. results, a consistent difference between the primary 3nd scondary hors wa died mary and secondary laboratory was detected (305%) for amps obtid din he it (~ 30%) for samples obtained during the first monsof dhe Pct Invision and 4 months of the Project. Investigation and ddan, ged na: nd ib rc additional, targeted intra- and interlab retesting concsh dcigho fs. ing confirmed these directional (higher) differes or cour lin, Even duced the ences. Per a court filing, Exygen discussed the use a prob finaly per samples cause as a problem ofinitially prepared samples idformer clan xSoplencncl used for internal calibration [see Supplemental Nic, Noe 7 (Jo 10.1200chy 090037. Material, Note 7 (doi:lO.1289/ehp.0800379. $1) Acid amps - 25000wee sd S1)]. Affected samples (~ 25,000) were retested ing crm sored in dhe jc i bark: using serum stored in the Project tissue bank; ql aurane ing, including sample quality assurance testing, including sample pice nd rp spedand con duplicates and replaced spiked and calibration mpi,wt su ep. Reto ew samples, was also repeated. Retested results mortal onerous fom ki demonstrated a consistent decrease from initial Fuk and cred cominwith these. results and increased consistency with the seconda. All aly rks pcre here ondary lab. All analytic results presented here includ oly rected lac fr thse acid include only retested values for those affected rum apie serum samples. For guaniciv ascment ofgual For quantitative assessment of quality san es rev, Anal st luc wer assurance test results, final test values were mach paripan: qual asarine vil. matched to participant quality assurance value fo hepian osecondaary, Ress ues for the primary or secondary lab. Results epi Is than the imiofdetain reported as less than the limit of detection (EOD) were trated conservatively and (LOD) were treated conservatively and cxuded from gusty sures nays, excluded from quality assurance analyses. Armen btm tw srwas csd Agreement between two measures was assessed "with beso diac, pce diene with the absolute difference, percent difference ole difece ewe los ddd by (absolute difference between values divided by ali man), 3nd code of vaiaion (GD value means), and coefficient of variation (SD ded by can). which were den summa divided by mean), which were then summasd can and i) sro de ch rized (mean and median) across the matchedamples rol samples results. Valdaion of lct medical digoss. Validation ofselect medical diagnoses. Paricipaneslrporingoncofth 15 cr. Participants self-reporting one of the 18 tareed tagnoss were aed provid the geted diagnoses were asked to provide the {imeani locuionof digas. Aer cbin time and location of diagnosis. After obtaining approprisce recor reese consent, ing appropriate record release consent, Brokaar nc, eqocsed3 coofsppoyn. and asisance comple the hh su Brookmar, Inc., requested a copy of supportin documencon from medical econ Drokamr, nc. a coniintd emote daa ing documentation from a medical record or pathology eprom heh cre prov. cleo for those xhrwise chic Class or pathology report from health care provid5 Cooper providesweecompen mrmbers unable 1 (vel (03 a cole ers. Cooperating providers were compensated SIO pr acca pate. For approxima Go se (those o ons ving nthe $10 per necessary page. For approximately 36.000 valde agnor, the Following viiniy). Fo thes paccipancs, lig 36,000 validated diagnoses, the following as worded eleporod dagaos documvea nmtitoo mf was recorded: self-reported diagnosis; supor onfmton. rapport (gion owed by emo complecon of he heh port (confirmation), nonsupport (negation), ising (rconds no obuine,osubi. suvey and pons leon ie missing (records not obtained), or substitufon (.c. documention supported 3 ifr. The remot parcpanc then completed tion (i.e., documentation supported a differcn dignos) h cmt dgnoss whee picboraotmy Heolf , cr: ded ent diagnosis); the alternate diagnosis where Sporn and yp ofdicmcnadtoend Doren. OF dc ol parca, appro appropriate; and type of documentation used or vein. Revi of medical records mtcly G00 pariopted v hos proce for verification. Review of medical records and deerminaion of dgnosde venice: (Fo penanr s cmme umct.on) and determination of diagnostic verificaSonwer prormed by nus cploed by Dror, nc. wa unable 0 comm tion were performed by nurses employed by Bok, nc de panicipans copie ible co Brookmar, Inc. Coming procedures Brook, In. ple de sey (nd wih rr Consentingprocedures. Brookmar, Inc., required da pripants read and "check to sccuraly complete on their bel) or required that participants read (and "check" omic) sn crdiciny scion ofthe thos phil us on 3pcr affirmatively) an introductory section of the eh suncy da capaind he purpose and omy sk. Th, hs groups ar ely unde health survey that explained the purpose and proceshoe Pfc, and1a0 dbene prec amon Pre arcs procedures of the Project, and risks and beneec paricpation. Ths langue s publically Date naysandrear Parcs fits ofparticipation. This language is publically avalible 3 par ofthe survey tok. Al par were mad nid cls or hc available as part of the survey tool. All parpansbmiing volun bod spl bt, icing Bboy normal ticipants submitting a voluntary blood sample comocd te Sond con md vies. go sol its: completed the standard consent and release forof he cinkl Bborsory conaced abnor vlc, anergy a gg forms of the clinical laboratory contracted for photon: Brokna, In. oboe pesos communication fom Brook for phlebotomy. Brookmar, Inc. obtained a septcome form fo the lsofmced. 1c. personnel with avi 0 ssk prompt separate consent form for the release of medi< econds esa or ignssvidaton, mafic tendon. Paganshso hod eal records necessary for diagnosis validation, which was obey ld (long with oor fhi PEC vil. which was subsequently mailed (along with cont ler and specie documentation Upon. completion of the Project, a cover letter and specific documentation ron) tothe eh care provider deni Brook, Tn. fled a dectonc dat et request) to the health care provider identified by heparin. vite Wd Cony Cour i Ny 2008. by the participant. The Project group at West Virgina Th dtsc ndte ahsucy, ini The Project group at West Virginia Univaethe See Pan obi cal iborsory and PFC alu, an mae of University and the C8 Science Panel obtained nail ewbound (RD) approval rom Sil doumens and eoof ponm. institutional review board (IRB) approval from ha own sions pemitin se To proce paricipnt privacy, he prod: their own institutions permitting access to deidenihd Projet dos. With ance fom ng oe suse cid the dt A dentified Project data. With assistance from Bok, Inc he CSePacobss mechani cued big sgh herd Brookmar, Inc., the C8 Science Panel obtained addons IR approval allowing ces an spchyoy f the Fel rm, additional IRB approval allowing access to Hae ds whih Flite omen. would nai and mabe seca 3 identified data, which facilitates contacting parGa for covs alent in Flupossm, denied dase for publicrch nc. ticipants for enrollment in follow-up studies. nplmensaio, Arnbybpe irg The C5 Scien Panel conducing Implementation. After input by the settling paris, rokar, nc. sd mull ens anys using the Proce crossscons parties, Brookmar, Inc. used multiple avenues public the Project, Communicadons dat colle and aa condoicsoiwnn to publicize the Project. Communications shou Pfc ighiky reguiremens, cal. independ, vival ax poiaion about Project eligibility requirements, enrollmde tcll, cion procedures, ms ne, bd tdi, anbycthesetednt ment, data collection procedures, time line, and femuncadon iced rics ofopen For omsenon pariepans dh C3 Sones and remuneration included a series of open macsings conduc in fcof thsei er Pant able vo nk Prjeccolced dos meetings conducted in five of the six water dic, Pct Web sc msg, phan with follow and longline sic. A districts, Project Web site messages, a phone bak, and pre cone i bo md, descrip,ofongoing ss vibe on bank, and press conferences with local media, an porn sue of memaion hgh the CB Since Fansweb se (C3 Sines an important source of information throughour tedurvionof he Projet. Pind 2009, out the duration ofthe Project. Brook, In. oho nin communi. tse barkofparicane frozen serum Brookmar, Inc. also maintained communicon iho hs crprovidesMecings vs sabloWeds Vigna Unive in cation with local health care providers. Meetings wrcondced to fremodi om Wich samples roel, hannd ,wel were conducted to inform the medical commuty shou rt prelim manne onc vith he IR proce nity about Project procedures, including media co roa, well a he formation govteWes Vii Univesty Ti eal record requests, as well as the information pric wk bepovdided pra Berke Th ers cnbe inked 0 ened that participants would be provided pursuant to hi Pos rion. Pred and may bed for cr their Project participation. Ef0cofne ful ccs for increted cred 0h PECphysio Efforts to ensure full access for interested pariciponts ncoded muliple sis, 12h Brookmr, Ine. contracted with che participants included multiple sites, 12-hr ay appoint, and dsby Wo Vigna Unversity SchadofViicine daily appointment availability, and disability cammodadon ncadin handicap secs 0 spor 0 dh genral public descripive accommodation including handicap access and assistance completing the health survey. Brookmar, Inc. also coordinated remote data collection for those otherwise eligible Class members unable to travel to a data collection site (e.g., those no longer living in the vicinity). For these participants, eligibility documentation was submitted via mail, followed by remote completion of the health survey and a personal telephone interview. These remote participants then completed phlebotomy at an identified, local, accredited laboratory. Of the total partidpants, approximately 600 partidpated via these procedures (Flensborg P, personal communication). Brookmar, Inc. was unable to accommodate participants cognitively unable to complete the survey (and without a representative to accurately complete it on their behalf) or those physically unable to travd to a phlebotomy site. Thus, these groups are likely underrepresented among Project partidpants. Data analysis and reporting. Participants were mailed individualized results for clinical lab tests, induding laboratory normal ranges and flags for abnormal findings. For severely abnormal values, emergency flags triggered a personal communication from Brookmar, Inc. personnel with advice to seek prompt medical attention. Partidpants also received a report of their PFC values. Upon completion of the Project, Brookmar, Inc. filed an electronic data set with the Wood County Court in May 2008. The data set included the health survey, dinical laboratory and PFC values, an image of eligibility documents, and record of payment. To protect participant privacy, the presiding judge subsequently sealed the data set. A mechanism is currently being sought wherdn an agency, likely of the federal government, would maintain and make accessible a deidentified data set for public research use. The C8 Science Panel is conducting analyses using the Project cross-sectional data collected and is also conducting its own independent, environmental and populationbased studies, also financed by the settlement. For consenting participants, the C8 Sdence Panel is able to link Project-collected data with follow-up and longitudinal studies. A description of ongoing studies is available on the C8 Science Panel's web site (C8 Sdence Panel 2009). A tissue bank of partidpant frozen serum was established at West Virginia University in which samples are stored, handled, and accessed in a manner consistent with the IRB protocol governing the West Virginia University Tissue Bank. The sera can be linked to deidentified Project data and may be used for further studies related to human PFC physiology. Brookmar, Inc. contracted with the West Virginia University School of Medidne to report to the general public descriptive 11887766 one17 en12 Dcen20b - Enon Hest Pesci VOLUME 117 I NUMBER 12 I December 2009 . Environmental Health Perspectives 2713.0004 2"/13.0004 8C8 HHeeaalltthh PPrroojjeecctt mmeetthhooddss aanndd rreessuullttss Hn aunsvskustroebsePocf Sumy tof wt dst es boc gap are. veweobgesehsecdoon BrM. Hower, summaries ofresults from the Project. Summary awer 3hl sh bb wi xhtac op To maneof pr. bent BVH calawetreCoompnletsed data are reviewable at a web site established for ht pe (C3 Hos Pj 209) ipa eden i ech wats diet wa win elepoted Belg snd weg hy that purpose ((28 Health Project 2009). "Fhe Co Science Pan and the Wet bad he sigwatnerdeicdt ac for ma sndsramate scl popular, pro. The C8 Science Panel and the West Vigioia Unie Pole gos i pr. which th paige peed sling. pions:Tootdemogoelpehaidack Virginia University Project group are preparing and mining erofasoss SHEAdocu and sf cponc Edaa Enral, Conpaens with ims paring and submitting analyses of associaion bewcen PFCs snd heh outcomes, doct he me of nln Fropuion fo Appsachia fom marion eprcats tions between PFCs and health outcomes, nino forperseJiouornw.Tshds mtsfo xhwarsdosvis cited thedossts (Habeio ao 300) fie intended for peer-reviewed journals. These il form prtof th vdnc chat willae fao d endso wr. SuMp at,p Take 2l Gok10e .1289) will form part of the evidence that will assist heGi Scene Fae fn marin he Court. arb the C8 Science Pand in meeting their Courtovoid obi to decir proc Results he wmofcnllmenr, mont poe appointed obligation to determine "probable I oe Supplemencl rl, Note 3 Proje enol woled 600. pros tian scored cunt seslenicn Ohio links" [see Supplemental Material, Note 3 (do10.12891chp0R00375.S1)] between mately 30% completed rgstrrion amd dhe (529)or Wot Vigna (45) 63%ofpi. (doi: 10.1289/ehp.0800379.S 1)] between PFOA powridheh cucomes. hah sry one (Flog P. prions _ tcpaae wre rent in quliing tr PFOA exposure and health outcomes. Date eaning Tn te Ro ph ofdas commit. PEC an hil bors din the ime ofthltpariipation D~ta cleaning. In the first phase of data caning, th TFGompanyconted sac ques anais were avilable for 5,000 paris Average monly comment bn she Project cleaning, the IT company ensured that qnesnn poreswer ates with duckies Pt Abhoghhike < 10yoreof thd was S910, with rollment peaking a tion responses were consistent with question ip pan nd mens opty well 5 hes pogorion without abl load ana) 2006 (5003 progThalmk "skip patterns" and menu options, as well as coving content coin nd fosmaning oulus hao onthe), hbortory ds propor of parpans quali rough ensuring consistent coding and formatting for qusion poe Fo thdedi wet revered sible > M00 oFhe Labeck Publ Sci Datei (34.6%) for question responses. For the deidentified e's tne Ad wee eubbed to shes Chen, Consent vith sei demogr. followed by Tope Plains (30.4%) sce. dnnaaatttaeepspoetote,tnettneitxaialtlllfyyieildiddesenntwitieffryyeiinnsggcruiinnbffbooerrdmmaattotiiooennl.i.mIIinnic ondpha of das dann, comple cvs whi,and cans nmcot and hyOBOES79SI). the second phase of data deaaing, completed olbobytrheCn3SimeneFaln aynd incon:Keswes bat san mond see. shown fn Table 1, an ciated 80.3% collaborativdy by the C8 Science Pant and or Virgins Unvesiy Pg cmco 79 asus godaf1o 37 of he popu, aden hewares ds West Virginia University Project team, coninuous vtabls wiecminedsnd duchies ta 100 eam wih an 3D og 390 3 cs din she valle period pus tinuous variables were examined and decision deswer crt for cutsand ming vi. 199year(s ppMl oc,Te ab 1 paredinth rjc, with a gyhigher rules were created for oudiers and missing valieaprsrt mags fo pls (0101205 OTS] Proporian of wamn compared with men ues. Lab-generated error messages for samples hat could notbe nly wre dered and Tay. peonfsdts (: 18years arcipating, Particbiywpaatetdiiornt that could not be analyzed were deleted and cl se or "oul Fo cial ab fs ofspae cvllen forte cure snake and Fo. 70.0% ofthe Auden ga results set to "null." For clinical lab results ihr ows ox igh thn the LOD. vas in, ad an additions 36% ep fom ion in Toppers Plans fo sbmot 95% J either lower or higher than the LOD, values `er repaced with 50%bel orshove he. ming, A aba proportion of lds. the Vilage of Pomc:Th x groups with were rephced with 50% bdow or above the oss apprLOD, pest {63.30 and ad (64.150) ck ren th lowes cited prion wit he lower or upper LOD, respectively. "Though rum sampleswe ayfor ceri program: Fu39h%ofrchi,de ch80 ey ro 5) andyoung children Though serum samples were analyzed for PY covery rime beet eee ir 10 PFCs, not all PFCs were detectable in all samples tr. Four PFCs (PFHS, PFOA, weight sedonbody vas nde (BMAD)pr. Scrum alysis rsulsfor10 PFCs samples tested. Four PFCs (PFHS, PFOA, FOS, PINAYweredeib n moes all <enl, and69%of dus ere cb (PFPA, PEHEA, PRIS, PEHpA, PFOA, PFOS, PFNA) were detectable in almost all 97% ample for the PFC, et els (> 97%) samples; for these PFCs, test results rid2sHo ha the LOD wr bt: Tel. tend arent pict pvt dic. reported as less than the LOD were substi- ih 033 neil (0% ofth fy MLEMIRIp pcpRb tuted with 0.25 nglmL (50% of the lower LOD af 03 gmk). TPh EC (Pe FHcA, 1 We to -- LOD of 0.5 ngimL). Three PFC.s (PFHxA, Prfip, PFDA)wee decoble in spp hn VET mime Seats Maenoue hewn PFHpA, PFDA) were detectable in approximad 50% ofthe ample rlsfo hee Pugs Oh) Org tiny _ (o_o mately 50% of the samples; results for these ge PFCs are reported with and/or without substiuion for ves reported sl han the 04 m6 sz sme ws ms mks stitution for values reported as less than the 10D.The PFC: (Pek. PUM,PFD) 510 om omoom om mom LOD. Three PFCs (PFPeA, PFUnA, PFDoA) eidefnt only4apeig ol rton. 138 Bow ow @ mom a were &tectable in only a negligible portion JSeorrrbir ana te 25 wBe mme ows ooms mmse woomr Moem hoheefrreteheoofriteinstcneldudsceadmipilnnleffsruuacrtnhhdederraaraneenaalnlyyodssteersse..pTTohhrstue,sd, pore er ind el 35 De omoms om om mom results reported here include 7 of the 10 tested TFCL (FHS, PRO. PROS, PNA. PRGA, 2.33 LE PFCs (PFHS, PFOA, PFOS, PFNA, PFI-IxA, PFHpA PDA) a Sm om Wn ae wa PFHpA, PFDA). Eriofmpartiacipattioniratos.Tnol 5.8 @omoE OW mom 8 Estimation ofparticipation rares. Total Profs pap wiam ibyvnive 58 Bm ows om om ws oa Project participation was estimated by water dichse mbesof pipinveg 5.80 8 om ow om om ma dents dividedby theton comemporaneous district as the number of participating resi- dpoenptusalacdtioiovnnidihenadtthbhaayttwtwahtaeetetroddtiasilsttrrciicoctnt..tWeWmaatpteeorrrdadinsisettroriiucst mo Xm wom om Wm ow om population was estimated using 2005-2006 `CCeennssuussppopoulap tioneusetstiil mmaatteeass ffootrrbblloi occkkgogrroouunppss,, tthheesmsmalallelessttCCeennssuussggeeooggrraapphhiiccuunniitt tthhaatt ccoouulldd uloy n Hock pape mer: Toman BA ms ge ms wa me be accurately identified. Block groups interecgwihwie ics wer demi, 50 secting with water districts were determined, nd he pono of exch tock pvp sw we om om om om Sppotoherwatetdiostnbuadondhe and the population of each block group was apportioned to the water district based on the ratio of water district area to block group area w',thin each block group. The nunaber of partic(pants resident in each water district was based on the assigned water district, that for which the participant presented qualifying eligibiliW documents, and stir-reported residence at the time of enrollment. Participation estimates for each water district yeas estimated for age and gender strata. Results Project enrollment totaled 69,030. Approximately 80% completed registration and the health survey online (Flensborg P, personal corunaunication). PFC and clinical hboratory analyses were avaihble for > 65,000 partici- pants. Although children < 10 years of age had highest proportion without available blood analyses (almost one-third), laboratory data were nevertheless available for > 3,400 of these pcphhhyiy,l,dr>>e9n9.77C%%oonofsfipspatraetrnitticdwippiaathnnttssregiiddioeennntatiilffiideeeddmttohhgeemrma--- salves as white, and educational attainment and income levels were lower than national averages. Parfidpants ranged in age from 1.5 years to > 100 years, with a mean + SD age of 39.1 * 19.9 years [see Supplemental Material, Table 1 (do(: 10.1289/Chp.0800379.S 1)]. Twenty-six percent of adults (_> 18 years of age at eurollment) reported current smokhag, and an additional 26% reported former smoking. A substantial proportion of children (63.3%) and adults (69.1%) lacked a regular exercise program. Further, 39% of children were classified as being at-risk or already overweight based on body mass index (BMI) percentile, and 69% of adults were classified as overweight or obese based on BMI. However, because BMI calculations were completed using self-reported height and weight, they may underestinaate actual population proportions. These demographic and health risk data are generally consistent with estimates for Appalachia from nationally representative data sources (Halverson et al. 2004) [see Supplemental Material, Table 2 (doe 10.1289/ ehp.0800379.S 1)]. At the time of enrollment, most participants reported current residence in Ohio (52%) or West Virginia (45%); 63% of participants were resident in a qualifying water district at the time of their participation. Average monthly enrollment in the Project was 5,310, with enrollment peaking in Ja,luary 2006 (8,003 participants). The largest proportion of participants qualified through Lubeck Public Service District (24.6%), SufSopulppllopewlememednetnbatyallMTMautaeptrepiraeilar,ls, TTPaalbablilenes33(((d2do0oi.i:4:11%00..)1122[88se99e// ehp.0800379.S1)]. As shown in Table 1, an estimated 80.3% of the population resident in the water districts during the enrollment period participated in the Project, with a slightly higher proportion of women compared with men participating. Participation by water district ranged from 70.6% of the resident population in Tuppers Plains to almost 92% in the Vilhge of Pomeroy. The age groups with the lowest estimated participation were the elderly (> 80 years of age) and young children (< 4 years of age). Serum analysis results for 10 PFCs (PFPeA, PFHxA, PFHS, PFHpA, PFOA, Table 1. Estimated percent participation by water district Participants Little Hocking City of Toppers Water Lubeck Pobtic Village of Belpre P~ains Association Service District Mason County Pomeroy (Ohio) {Ohio) (Ohio) IWest Virgi:nia)[West Virginia) (Ohio) Total Age gmL~p 04 5-t0 11-14 B24 15-t9 20-24 25-29 :30-34 35-39 40-44 45-49 50-54 5-84 ~59 60-64 5655~5"9 70-74 37>538-0079 TToottasl Total _> 20 Sex FO Ma~e Pemale 39,6 54,2 54,8 79,8 7t .7 81 85,6 732 903 | ns Te ;0,1.9, 82,0 90.7 9.6 72.5 77.6 88,2 74,6 84,5 87.6 76,1 92,9 873 76.7 90.8 94,8 75.7 86.2 94:6 71,3 85.0 85,8 79,9 84,8 & nm om 89,3 69,6 84,1 8,3 TI,3 82.2 2 = = 89,4 672 88,8 8.5 57,7 78,6 E7591n..88 35B548,.442 54a51g.,29 685,6 07&86 82233 87,8 7&2 82,6 mms 85.0 69.6 86,1 7~,6 ms80,9 83,8 38.5 72,3 92.2 ao107,5 81.0 73.2 81.6 94.5 100.1 89.6 79,; =89,S 96,8 E91,d3 84,4 u6395g.38 a83s.9 85,2 ow82.8 85,0 39,5 36.2 45,5 79,8 87.7 77.0 9&8 88.6 87,2 mm 96.9 t 10,2 94.6 90,0 98.9 82.8 90,5 86,7 8t,9 93.7 92.7 86,1 94.6 103.2 88.7 91.4 94,9 88.4 90,8 1092 85A 83.3 102.5 82,8 us78.1 82.8 F:78,8} 74.0 98.8 8L2 ws101,6 85.t 88.6 82,0 =n 94.3 75.6 E 58,3 31.0 68322..26 64a02r,,1t "823.3 9at e.6 @803 83.1 94,8 8t.0 Me79,9 84,8 we89.2 93,6 ow78,8 8t,8 EvoraHest Tse ka 17 aa 210K 00 1877 Environmental Health Perspectives vo~u~E 117 I NUUBR 12 I December 2009 1877 22771133..00000055 un frisbeeot a. Fri:sbee et a:l. PEOS, PENA,PFDA, PUM, FIDO)were perform. Figure 1 highlghpcbryangse oer isgl group For PHS and PENA PFOS, PFNA, PFDA, PFUnA, PFDoA) were retrain, TH de oe ad cle BE. Fe C3. ehopin cin avaihble for 66,899 participants. Table 2 summaiz he propoftosre tpilos wnih (PFHS, PFOA, PFOS. PENA). For cach. comentioern rd m chi marizes the proportion of tested samples with + decbic RC conenion snd the um: median concnvations wee hight in mle igure 2 compar Project ress for a detectable PFC concentration and the ntmaof samples for hich 50% ofthe owes in mare a groups, For PFO and PFOS ths tn oe PFC with tls ors two bet of samples for which 50% of the lower LODwaite. (Figur 1A) poplton med cones mio reprisctaine NHANES samples LOD was substituted. "Tibi3 reports population ummaty ss hms demomitat 2 -abped pcs, wih An impor free betwen NHANES Table 3 reports population summary staoes fo se een PEC, shod by 0k WES vos 2 Yount ag Sows Kowa ndPg ssl' he nto of chien tistics for the seven PFCs, stratified by sex nds groups. ecu ofpoplhioon: vhsnyoun.10 abd bk fe proups, < 12 yous fa i che Pcs, bough hi and age groups. Because ofpopuhtion homorecto by Cmte ws a +0 When Popaiion somcerestoms Pret og pov Bhely 1 av int geneity, stratification by ethnicity was not performed. Figure 1 highlights patterns by age and sex in the four widely detectable PFCs (PFHS, PFOA, PFOS, PFNA). For each, median concentrations were higher in males in most age groups. For PFOA and PFOS (Figure 1A, B), poptdation median concentrations demonstrated a J-shaped pattern, with higher values in younger age groups, lowest values in young- to middle-adult age groups, and highest population concentrations in Table Albinof tsc n cicl astor or PC hems sr (St vio: umlpimlpacstoon v5,e0l00 poFpoorlallriPonFCesis inexp Table 2. Availability of delectable serum conce~rations for PFCs show~ as the number (%) of samples. me e pwirtiorvcynn we ham"iio GaAOODS% tfherPrioffcraeccnedscoewndecreNenHtbrAtiNonrEsSdprofolrrc.PhFOTfAho.e PFC PFPeA EH am4 g Tan Tan iSom nh(e199s9-3p0 oor d bd me on PFH~ fi Ee Ti Ee en PFHS Jiyd ssommmeas) a"mgoens aSo0n0 ifrences were so observed for PFHpA PFOA Ja Bonney Si RY PES [57.1% (1999-2000) and 73.6% PFOS jit Em iia Bi (003-2004) larger) and PENA (178% PFNA iy Samia smn 00 (1995-2000) and 39% (2003-2004) ger PFDA Fn Sgsen amma 080 In comrat, the Project population hd + PFUnA Fo Sin Bima 000 365% (1999-2000 md 150 2005-2000 PFDoA No. (%) with detectable concentration 3247 (4,9) 35,574 (53,2) 65,499197,9) 25,095 (37,5) 66,857 (99,9) 66,000 (99,6) 65,348 (97,7) 30,996 (46,3) 5,035 (8.7) 488 (0.7) No, (%) with concentration < L0D 63,652 (&2) 31,326 [46,8) 1,400 (2.1) 41,804 (62,5) 42 (0,t) 299 (0,5) t,551 (2,3) 35,903 (53.7) 61,064 [913) 66,411 No, (%) with substitution of 50% of LOB [&25 rig/m1_) 0 (0,0) 0 (0.0) 1,400 (2.1) 0 (0.0) 42 (0.1) 299 (0.5) 1,551 (2.3) 0 (0.0) 0 (0.0) TT ng BE over oma mefor FnOS Denominator is total possible samples 166,8991. older adult age groups. For PFHS and PFNA .(Figure 1C,D), the highest population median concentrations were observed ha children. Figure 2 compares Project results for these same four PFCs with results from two nationally representative NHANES samples. An important difference between NHANES and Project results is the inclusion of daildren < 12 years of age in the Project, although dais Project age group is likely to ha~,e a minimal impact on overall population results in a sample size > 65,000. For all PFCs except PFOS, serum concentrations reported for the Project exceeded NHANES results. Tne largest differences were observed for PFOA, where the Project population had more than a 500% (1999-2000) or 700% (2003-2004) larger geometric mean. Smaller but still substantial differences were also observed for PFHS [57.1% .(1999-2000) and 73.6% (2003-2004) larger] and PFNA [178% (1999-2000) and 39% (2003-2004) larger]. In contrast, the Project population had a 36.8% (1999-2000) and 7.1% (2003-2004) lower geometric mean for PFOS. Table PopinionsrmconcomrtionosrseenPGs i). Table 3. Population serum coeceetrations for seven PFCs (nglmL). Age/sex Tw < 12 years en Female wneC onwen Mate e5Genonwen Total town 5eGonwen 12-19 years a an Female wnGtoonwen Male tCwonmnpenen Total Daw Gtonwen 20-39 years fn Female wenG5 oonwen Male G@dGeeoooninnwweenn Total Measure Mean Median Geomel~ic mean SD Mean Mediae Geomelric mean SD Mean Median Gee meVic me an SD Mean Median 6eomel~ic mean SD Mean Mediae Geometric mean SD Mean Median Geomel~ic mean SD Mean Median Geometric mean SD Mean Median Geome~c mean SD Mean Median Geomel~ic mean SD PFHxA~ PFHxAb PFHS PFHpA~ PFHpA# PFOA PfiOS PFNA PFDA~ PFDAb wu ow on ou om om ow ww 0,9 1,3 10,6 1.1 wool soo mo ow be 1 0 ow 0,7 1,0 61 0.7 1 Bn 4 x ow noonow 0,7 1,t 65 0,7 Bol om om ow ow ou ow ow 0,9 1,0 130 1.3 Boom ou dE mom so6ow 1.0, 1.3 1Z6 1.1 woo Sow mm om dom ow 0,7 1 ,O 69 0.7 M4 mu mom noonow 0.7 1.1 L4 ,0.7 mow BoM om mono now t.0 1.0 183 1.3 oowoom ou Ww Tome ono ow 1,0 1,3 116 1.1 ooh sooo mo om ow to 0 6 0,7 1,0 6,4 0.7 m4 x om noonow ,0.7 1.1 7,0 ,0.7 To ws Bd ws mun ow 1,0 1,0 159 1.3 1,4 73.0 22.6 1.g 0.5 0,7 1.0 30,7 19,9 1.6 0.5 0,6 t.1 34.8 19.7 t.7 0.4 0,7 1,5 120.1 t22 1.4 0.3 0,2 1.5 6E1 24.6 15J, ,0.5 0.7 1 ,O 35.1 213 1.6 0.5 0,6 1.1 39.1 21.5 1.7 0.4 0,7 1.5 !29.1 13.4 1,I 0.3 0.3 1.4 77,6 23.6 1,9 0.5 0,7 1,0 32,6 20.7 1,6 0.5 0,6 1.t 36.9 20.6 1,7 0.4 ,0.7 1,5 124,9 13,1 1.3 0.3 0,3 ww oe wo uz wm om ou sw 0,8 1,4 62 0.7 1.2 51,0 2&1 1.4 0.5 0,7 ol wooo mom wo 1 ou 0,5 1,0 37 0.3 0,9 22,1 18.0 1,3 0.4 0,6 0 1 6s Wo mo ome onoonoow ,0,5 1,1 4,0 ,0.5 1.0 25,1 17.6 1,3 0.3 ,0.7 Bo; so aE ome wo ow 1,0 1,2 9,5 0.8 0,9 85.2 1L0 0,7 0.4 0,3 Wom mo ds Ge om to@ ob 0.9 1,4 &3 1.0 1.5 @.4 23.4 1.6 0.3 0.7 08d mop wm ome 1 aw 0.6 49 0.6 1.0 30.2 20,5 1,6 0.5 0.7 0 1&0 12 wom 15 Bw 0.6 53 0,6 1.2 33,9 20.6 1,5 0.3 0.7 Boonoom ow on ows won uw 1.3 1.5 118 1.2 1.4 1~.8 122 0.8 0.4 0.3 WoW Tmo os; wm om 1% ow oo 0,9 1,4 7,3 0.9 1.3 59.9 21,8 1,5 0.3 0,7 Gd Boo om wm Moo 6 0.6 1,0 4,3 0.6 0.9 25.7 193 t,4 0.5 0.6 0 1 4 Bu momo bow 0,6 1,1 46 0.6 1.1 29.3 1&1 1.4 0.3 0,7 Bono fo 2 om ow a ow 1.2 1,4 108 1.0 1.2 96.2 12.0 0.7 0.4 0,3 ow om os ow om ow ou ow ow 0,8 1,4 &0 0.5 1.0 42.3 16,6 1.4 0.3 0,8 od om oo 0 md Ww 1 ob 0.3 1,0 2,2 0,3 0.8 17.0 14,8 t.2 0.5 0,6 03 1 22 0 0 We Me 1 Bow 0,5 1,1 2,2 0.4 0.9 19.8 l&0 1.2 0.3 0,7 Boom Bo moms wooo oom 1.0 1,2 &0 0,6 0.8 118.3 9.7 0,8 0.4 0.4 Ios omo oo a We ae wooo 1,0 1,5 53 0.6 1,2 76.5 24.3 1.7 0.4 0,8 od ooo om om dnb 0.6 1,0 &8 ,0.3 0.8 28.3 22.2 1.6 0.5 ,0.7 0 02 3% 0 Wm om on Bw ,0.6 1.2 3,8 0.4 1.0 33.4 20.7 1.6 0.5 0.7 Woo oowoowm om mm mo ow ou ow 1,4 1,6 7~ 0.7 1.0 2~.1 12.8 0.8 0.4 0,8 oo Ham oo on Woman 0,9 1,4 &0 0.5 1,1 58,1 20.1 1,5 0.6 0.8 od mos 0 mn mo uo oo 0,5 1,0 2,9 0.3 0,8 21,8 18.1 1.4 0.5 0,7 0 1 3 0 0 momo om now 0,6 1,2 2,9 0.4 0.9 25,2 16,8 1.4 0.3 0.7 Tow 8 wm we me woo mw 1.2 1,4 5~ 0.7 0.9 166.6 11.9 0,8 0.4 0,6 Cont Con~u~ 11887788 one 17 a 2 Dc 25 EveHenshetspecsies VOLUME 117 I NUMBER 12 IOe~ember 2009 . Environmental Health Perspectives 22771133..00000068 C8 Healt Project methods and rests Hn C8 Healt,h Project methods and resu:l:ts Unsfutdsopunmc Seamsho Lubeck bl Se Disc hide igh OA. The demagphic drat snd Unadjmted, nonparametric Spearman's rho kris oa ys ws porn pod lo EHR PEO, PAam hh i i oro ion toot rank-order corrdation analysis was performed fo 1 ins en DPC) fo oval] DEhDe h,h soPFSfund he cid, mosh i, pbc. for 21 pairings (seven PFCs) for the overall Bolton 5 ek coratos ban Fade de oofBO mt. pedombosl wh ih bsof poptdation. In general, correladom between ETT wer Tow. Mode conciution "T3Smihmees ls bo the guy doaion ad erebt se tl the PFCs were low. Modest correlations CI weehedSn pf sane sii To bot aoe a adhe soobokY snd et (* 30%) were observed between the pairings of FEMSPRON, PETS_PPNA, DEOR-PTOS: both i win te rms) snd ba 41 Skins sch 3smokin and PFHS-PFOA, PFHS-PFNA, PFOA-PFOS, nd PEO PFDA ares coaton wre meh otc he pray and sont mais Chlngs pod by the i and PFOS-PFDA. Larger correlations were ced ewe FH a TFAOA 40% 1b wee shoe fo FF. PEO, tionof he Clas. special i prolonged observed between PFHpA and PFOA (- 40%), TRIS wd TEOS 300) FOSsnd PENA PROS. id TFA. Te meio si 50g) ipo prod sod tot of PFHS and PFOS (* 50%), PFOS and PFNA 50%, ad ENA and PFDA - 60%) fac for PFO 1nd ROS was S5% and rade caplet and holbed (- 50%), and PFNA and PFDA (* 60%). No Gucci iffzoonin comiions ar. 406%, rapectely, wheres she medium cxporee, Prectde sm iat domination No discernable differences in correlations pat- cos whe id bone dls nd nea duflenc fo FFOR an TFOS was of tt tos] hg papal, Howe a terns were observed between adults and chil- on ar berve se ir ot hows cs 167% and 14%. tei. The J tbl points oe 80%. dren or between sexes [data not shown; see Soot Vast h3oGATnOS ns het abo Wor i of Sw pal Be oc wt Supplemental Material, Figure 2 (doi:10.12891 frst ened foc ich. or PgR ad dic purhod in te Pe: shh ehp.0800379.S1)]. "Tk pts rum PFCcancion. PFDA i bt po ne atement 37a Foes paints stl le Table 4 reports serum PFC concentratiom, waetalorn mFdta p Loley uHlong koh eForde toodti1 psrobabsle etosf om. water district. Participants in Little Hocking Vt Rion bd Nghe et of Discussion isos g begbe] Water Association had the highest levels of PFOA. 70% Higher thn i mt aap Ti ae and ue suey resi om Somumanion snd mon compen PFOA, > 70% higher than the next group, aici wih pve wel. For li PEGs 1h pv slcan apecnent of 2 co com 0 parton. Th Bh oe partidpants with private wells. For all PFCs ton FON fh 17 paripatusly. sci os snd cospared bk of polo aii sd he ih oe other than PFOA, the 157 partidpants qualifynihcommit sc de os pin O30) pond (me $70) 5one 0. is ing through contaminated private walls had the Ee sce. upon ried noes mina wih) vat ud compl ofBeh highest serum concentrations. Participants in Lubeck Public Service District had the highest reported values for PFHxA, PFOS, PFNA, and PFDA. qtle highest values of PFHS were found in participants in the City of Belpre, Ohio. Table 5 stunnaarizes results for the qt~ity assurance analysis. The highest agreements, both intralab (within the primary lab) and interlab (between the primary and secondary lab), were observed for PFHS, PFOA, PFOS, and PFNA. The media,a intrahb difference for PFOA and PFOS was 5.5% and 4.06%, respectively, whereas the median interlab difference for PFOA and PFOS was 16.7% and 14.01%, respectively. The least agreement, either intra- or interlab agreement was observed for PFHxA. For PFHpA and PFDA, intralab but not interlab agreement was observed. Discussion This unique and large survey resulted from the pretrial settlement agreement of a class action lawsuit and a court-supervised health study of a population (n = 69,030) exposed to sustained environmental contamination with PFOA. "lhe demographic characteristics and health behaviors of die participants reflect that of the affected, mosdy rural, Appahchian communities: predominately white, with levels of education and income lower than the national average, and higher rates of obesity and oilier health risk behaviors such as smoking and inactivity. Challenges posed by the definition of the Class, specifically the prolonged (50-year) exposure period and inclusion of residential, employment, and school-based exposure, preclude an exact determination of the total eligible population. However, a reasonable approximation suggests that 80% of the current population in affected water districts participated in the Project, although 37% of Pro)ect participants resided outside an affected water district at the dine of thdr Project enrollment. It is probable that a combination of public concern about chemical contamination and monetary compensation contributed to pattidpation. The high rates of population participation and the high rate (estimated at 80%) of online (vs. paper survey) enrollment and completion of the health Pr Table 3. Continued To Ve or Age!sex Measure PFHxAa PFHxA# ?FHS PFHpAa ~l-HpA# ~FOA Pt-0S P~NA PFDAa ~I-DA~ Tom 40-59 years iy wn ms un wm om 1 ow ow Female Mean 0.8 p= Gown now momo nou ow Median, 0.5 Ewen NB om 6 Bom Bou ou 6eomel~ic mean 0,5 & Bono o8 Hoa 8 oa on on SD 1.0 ee a onoo% Bom om OBOE ou Male Mean 11,9 i 8 on Hf o% 8 om om o8 ou ow Median 0.5 Cnn 8% mB mom Bow ow Georne~'ic r~ean 0,6 8 BoB o& 8 Boa mou 8 0 8D 1.1 dn aoonowo% Bow oR owoE ou Total Mean 0.9 fe 8 hooB 8 4 BoB oR OE OU Median ,0,5 Eee oH BH O8 BOB ON OH OB 6eomel~ic mean 0.6 & Boonoao8 Boa ow ou o8 on 8D 1,0 sto 60 years = www ow ou ow om on ow ow Female Mean 0.8 te. 8 B ou 8 WE BoE ow Median 0,3 Een & 3 oR ow BOW OM OB O& 9 6eomel~ic mean 0.5 & Gohoo# oN BoE Bon ou ou SD 0.9 ln oR 8 ow Bom omouno% ou Ma~e Mean 0.9 jo 80h of 8 ow Wm oE oR Eo Median 0.3 Een oB HouoB BOB OBOE OY Geome~'ic r~ean 0.5 & Bono oN 8 oa Boa Non SD 1.1 [I aon o% on BOW omonou ou Tota~ Mean 0.8 fe gon 8% oR oWmoE oR o 8 Median 0.3 Bonn 8: BN om 0b oom Bou ow Geomeldc mean 0.5 & Bono non oS moa 8 ou SD 1,0 Toten Tol~l ~ulatiee TS ww ow ow ou om om os ow ow Female Mean 0.8 1, 8 nn o5 8 8 = HoB o& Median 0,5 Eonn 82 lB om Bom om oB ou ow Geomel~ic mean 0.5 & BonoE 8 Bo o@ Boa on on SO 1.0 dn a oonooB 8 BW oR Bou ou Ma~e Mean 0.9 = 0B o% 8 8 HB % & 8 Median 0,~ Cnn 8 B&B om om Bow ow Geome~'ic mean 0.6 & Boon o& 8 5 a4 mou oN ou 88 1.2 hn oonomo% Bom oBE woe ou To~l Mean 0.9 ie. Won o% 8 =m om ono ow Median 0.5 Een % BB ow BomoBMOH oR OW Geomel~ic mean 0.6 s BON wo 1 on ow 0 ob SD 1,1 ;,4 3 3 01.5 t,0 2,4 ,0.3 ~,1 23 0.4 1,1 32 0,8 1.4 43 0.6 !.0 &4 ,0.3 1,2 3.5 0.4 1.2 !6,8 ,0.8 1.4 4,0 0.5 1.0 2,9 ,0.3 1,1 28 0,.4 t,2 t ~ ,9 ,0.8 1.3 4`7 0.7 1.0 3,3 ,0.3 1,1 3,4 0,.4 t,0 5,3 1.1 1.5 4,~ ,0.6 1.0 3.4 ,0.3 1,2 3A 0.4 !,4 53 0,.9 t,4 4.7 0.6 1.0 3.3 ,0.3 1.1 3,4 0.4 1.2 5,3 1,0 1,4 4,3 0.6 ;,0 27 0.3 1.1 28 0.4 1,1 6,2 0,8 ! .4 5,9 '0.7 1,0 3.8 0.3 ! ,2 40 9.4 1,4 128 &9 1,4 1 0.6 1.0 32 0.3 1.1 3.3 0.4 ;,3 l&0 0,9 1A 802 20,8 1.5 0.5 0,8 0.8 252 11,7 t,3 0.3 ,0,7 0,9 30,4 16,9 1.3 0.4 0,7 1.2 260.7 14,2 0,8 0.4 0,4 1.2 120.4 26.6 1.~ 0.5 0.8 0.8 37.7 23,5 !.5 0.3 ,0,7 !.0 43,8 22.3 1.5 0.4 02 !.2 33{3.0 !63 0.9 0.8 1.! 1,2 99,4 23,6 1,6 0.5 0.8 0,8 302 20,5 1,4 0.3 ,0,7 0,9 36,2 19.3 1,4 0.4 0,7 t.2 301.4 15,7 0,9 0.6 0,9 1,4 107.0 2&2 1,5 0.5 0,8 0.g 41,0 24,2 1,3 0.3 0.7 1,0 44,2 22.9 1.3 0.4 0,7 t.6 199,9 19.7 0.8 0.4 0,4 !3 120,8 3D,3 !.5 0.5 0,8 0,g 42,8 26,! !.4 0.3 ,0,7 1.0 47,2 24,7 1.3 0.4 0.7 1.3 394.1 23,2 0.9 0.4 0.5 t.3 113,8 29.2 t,5 0.5 0,8 0.g 4Lg 25.1 1.4 0.3 ,0.7 1,0 45,7 23`7 1.3 0.4 02 1,4 311,7 2~,5 0. 0.4 0,5 1.2 68,8 20,7 1,5 0.5 0,8 0,8 23,6 17,6 1.3 0.3 0,7 1,0 27,9 17,0 13 0.4 02 1,2 190,6 14A 0.8 0.4 0,4 ! .3 98.2 26.0 !.7 0.5 '0.8 0,9 33,7 22,9 1.5 0.3 0,7 1,0 39,4 21,9 1.5 0.4 0.7 13 284.3 16,5 0.9 0.{~ 0,8 1,2 82,9 23,3 1.6 0.5 0,8 0.9 28,2 20.2 1.4 0.3 0.7 1,0 32,9 19,2 1.4 0.4 1,2 240,8 15,6 0,9 0.5 0,7 TET SR RR ~Subst~tution w~th 505'0 of LOD for values ,reported as < LOD. ~No su:bstituti~n for wlues repo~# as < LOD. Enon Hoth paces +vu 1 wa 11Onn 9 1579 Environmental Health Perspectives VOLU~E 117 I NUMBI~R 12 I December 2009 1879 22771133..00000077 un eats Fri:sbee et al. 3iin iH S" ol . 7.00 "6.00 zi -wl4.00 -J3.00 Figure 1. ==] a Ene e a Age (years) SE 3-i 3g=. 1o Ei: wN E SEIe SB ag [flp moe E B T A hi dr reeiteoodl eaSti nE Tnssee r a C e nE eare iTbat lR i ioelreur ae r gnlohm nh ce E bgroae ytofoc nahcodsbdt p a ouT pd esdpR omnpeotsoepe T pweon loears s niedas1mynEnsPen0tOosE]olde8NdSn Age (years) survey in a rural, poor area may provide useful lessons for future popuhtion surveys. As antidpated, study serum concentrations of PFOA, the identified environmental contaminant, deviated markedly from those of a representative, national sample in all affected ~ater districts. "]he unadjusted population geometric mean of 28.2 (median, 32.91) ng/mL was 6- to 8-fold higher than nationally representative values from the NHANES study. However, observations of serum concentrations for PFHS and PFNA that were higher than nla~taitioonnaall ssaammpplleessbbuuttccoonncceenntrtraattiioonnssffoorr PPFFOOSS. lower than national samples were not anticipate& "Ilae distribution mad pattern of PFHS and PFNA concentrations is not similar to that of PFOA, suggesting a possible exposure source other than die facility identified as the source of PFOA exposure. Comparisons between these two studies are interpreted within the context of possible differences in laboratory analytic techniques (although both studies used solidphase extraction followed by high-performance liquid chromatographyttandem mass spectrometry) and measurement accuracy across a broad spectrum of concentrations. Discernible sex differences for PFOA serum levels in most age gronps are consistent ctRae trun) AAT FAo Iyrs). Age (yea~) 10-19 ~ )0-~ ,10~.9 E~0~9 60~69 7~79 Age (years) PFC concefltrations ~r~tified by age and sex: (A) PFOA, (~ PFOS, (~ PFHS, and (D) PFNA. acions. Theeffe indoifr nhigghser serum conny with national findings in less exposed popu- lations. The findings of higher serum concentrations of PFCs in children, particularly Fems~e 8 HBel'lh Pro ect I NHA~ES 1~ II N P~ANI~S ~2m~@~ Fem~te 19~2 IE' 1~8 lU,4 Ma~e 12-Dyeers Z0-3~ years Mate |2-19yeats 20-39 ve ers 233 19.1 16,8 12H~1 4~5U ye ers | = lei~o Tos PFOA (ng/mL) 40-59 ve ers E ed PFOS (ng/mL) 33 1.4 123 2.8 1,4 = HI; | = a, PFHS (ngin]L) PFNA (ng/mL) BE,aa oe ren Ae OA Figure 2. Geometric means (ng/mL) for PFC serum concentrations for C8 Health Project results [versus two NHANES samples (2003-2004; 1999-2000)1: PFOA (A), a PFOS (B), PFH8 (C), and PFNA (O). a0 ten Somer morn 1880 VOLUME 117 I NuMe~R 12 IDe~ember 2009 . Envlr~mental Health Perspe~lves 22771133..00000088 8C8 HHeeaalltthh PPrroojjeecctt mmeetthhooddss aanndd rreessuullttss Hn for PFHS and PENA, warrant forthe suady. Lie Hocking Water Aociton dic isa smaller snle of Like Hocking residents for PFHS and PFNA, warrant furdaer study. Although thes finadreiunnadjgustsed for consistent with wer quality measurement (age. andsexadjusted mean of228 ng/ml Aldaough these findings are unadjusted for pon confounders, higher concntaions orsfom he fected wie dts [any 1ported herevs. 448 nL. Emmet a1 potential confounders, higher concentrations {nthe younger ae groups s counter0 ra ofwhich arc publically availabe also sc 2006). Alhough the won or thee ie in the youngest age groups is counter to tradina apecaoifboilngsi burden paral Supplement trial, Note 2 (do10.1289/ ences se no cls, represcactinencs ofthe ditional expectations ofbiologic burden paralIdlingcumulative cvirnmentl posure. <hp.0800379.51)]. Hower, he population samples and study ie peiods ae posible leling cunmhtive environmental exposure. "The oberaion ht the highest popu PFOArlsfo LinkHocking ie ian. planation. Th sm borat performed The observation that the highest populaon burden of PFOA wis found in the tly lower tha thoseprevio reported in PFOAsniancspc ssy. lation burden of PFOA was found in the Little Hocking Water Association district is consistent with water quality measurement reports from dae affected water districts [many of which are publically available; also see Supplemental Material, Note 2 (doi: 10.1289/ ehp.0800379.S1)]. However, the population PFOA results for Little Hocking are substantially lower daan those previously reported in Talo Age. an soxato or PE concentrations bywar ditt not. Table 4. Age- an{~ sex-adjusted serum PFC concentrations by water distri,ct (ng/mL). WarGit. SS 3 Water district PFH~~ PFHxA# PFHS PFHpM ---- -- -- -- -- -- -- City of Be~pre lOhio) em ww se ow ow ew aw 1m wo; Mean 0.86 1.41 5,82 0,64 s wow ono o@ ze ow om on a SE le tog Ws Asociihoonl Little Hocking Wate~ Association (Oldie) 0,01 0.02 0,11 0,01 an os te sm us 1m ws po wo om or Mean 0,85 1,39 5,70 1,15 5 ow om on om zm ow om on on SE 0.01 0,02 0.09 0.01 a] Lubeck Public Se~vi,ce District [West V,iroinia) en woos sm oe ws ms ous wo oe Mean 1,02 1,51 5,58 0,61 5 on om om on on mor om om on SE 0,01 0.01 0.08 0.0I MesonCoty etVig Mason County (West Virginia) en ms ws ew om ww nn 1m oe Mean 0.72 1,28 4,15 0.38 3 Wok om ao oe 2m ow om on an SE 0.01 0,02 0,09 0,01 Tops 1) Tuppers ~PIains (Ohio) on om ts we eo om en am ow 0m or Mean 0.84 1.38 4.48 0.43 5 ow om on ow i om om on on SE 0,01 0,02 0,08 0.01 ViofoaorOntol Village of Po~eroy (0hie) wn mm as ew om we mw 6 ww Mean 0.83 1.38 4,25 0,38 S wom on oo od sm om om om SE PolVeegi s PrJvat~ We~l lWest Virginia or Ohio) 0,02 0.03 0,17 0,01 on os uw 9m wwe ws ms wow Mean 0,65 1,88 9,27 0.82 = 0B on on ow on wm iz om on ow SE 0,08 0,16 0,79 0.07 Ee ey aSubstitution with 50~o of LOO for values reported as < LOD. ~Nc sabstitution for values reported as < LOO. PFHpA# 1,10 &02 1.86 &01 1,05 0,01 &83 &02 &91 0,02 &83 &04 1.48 &14 a smaller sample of Litde Hocking residents .(age- and sex-adjusted mean of 228 ng!mL reported here vs. 448 ng/mL; Emmett et al. 2006). Aldaongh the reasons for these differences are not clear, representativeness of the samples and study time periods are possible explanations. "Ihe same laboratory performed PFOA analysis in each study. PFOA 42.96 2,48 227,59 2,03 92.36 1.78 16.00 2.06 42.07 1,96 15.96 3.83 132,56 18.41 PFOS 23,18 0,16 23,47 0.14 24,96 0.12 23,01 0,14 22.29 0,13 20,97 0.25 26,15 1,22 PFNA 1.50 0.01 1.60 0,01 1.64 0.01 1.59 0.01 1.50 0,.01 1.46 0,02 1.67 0,07 PFDA~ 0.47 0.01 0,.50 0,01 0.55 0.00 0.45 0.01 0.53 0,.04 0.47 0,00 0,,40 0,01 PFBAb 0,73 0,01 0.77 6.01 0,82 0.0I 6.72 0,01 0.74 0.01 0,69 0,02 0.81 0.08 Talo Summaofryrs. nd tor avy ase Table 5. Summary of intra- and interlab qual~ assurance. EE ---- rT ---- -- Intmlab comparisons~ lnterlab comparisons~ Coposmasse TWpTmw)S RObhuTomrg)Ee dMfieewkrs ofteiars oCfofaionnt MwuleSilghbl) SGbhoamnm)h aAtuees _fofwowdcs ofOvfaifn Compound/measure Primary lab test results (ng/mL) Primary lab 0A sample (ng/rnL) Absolute difference Pereen$ difference Coefficient of variation Primary lab test results (ag/mL) Secondary lab QA sample (ng/mL) Abso[ute difference Percent difference Coe~ci~nt of variation we PFHxA Noofsaps oem mw Um Mee MMM No. of samples ow oh hm Em 0 1 mors Mean eon foo a Wma 0% Median msPFHS Moose 176M iz oz am am 6 9 2 No, of samp lea en wT Yo Ye Yu Ts is ho Cam Cn Mean aon a0 ow wm ow 5 2 oom 0 Median ist P~HpA Nootsas w oe ow aw wm @ ww om No. of samples en woh Ne Is Ty Ga um Mean in os a ao ie @ san 0 Median PFOA Moors 1m mm mm am am um mu No, of samples en mo me Tu Mae Mh fms fm mm Cu Mean aon mom ou Wow wm Bown oo Median EaPFOS Noses Am mm mm mm sm 2m No, of samples en 2 mo Cw Tae Cw zm 3 me Cw Mean eon Bown Wn wR Bum oo Median EnPFNA Noone 126 12 ie ize mw am am uw a No. of samplea en Me Yh Yee M4 1] 1 a Can To Mean Jian Wow eo " 2 oooan 0 Median PFDA No toms ww ss os sm " EE No, of samples J 0 hor ew or 08 tu 0 me To Mean eon BY on ww u ts Bano Median 664 1,3 1,0 1,236 4,6 3,1 446 t,2 0,9 1,269 77,3 25,3 1,261 22.9 19,5 1,246 t,6 1.4 566 0. 0,7 612 1,3 0.9 1,241 4,6 3,1 434 t,2 0,9 1,269 80.4 25,3 1,261 23.2 148 1,243 t,6 1.4 570 0. 0,7 574 0,3 0,1 1,234 0,4 0,2 410 0,t 0,1 1,269 9,7 1,4 1,260 2,0 0,7 1,240 0,2 0,1 516 0.1 0,0 574 18,3% 11,8% 1,234 9,4% 4,9% 410 8,5% 4,2% 1,269 10.1% 5,2% 1,260 8,4% 4,1% 1,240 9,0% 6.5% 5t6 6.% 0.0% 574 0.1 0.1 1,234 &l 0,0 410 0,1 0,0 1,269 0.1 0,0 1,260 0,1 0,0 1,240 0,1 0.1 516 0.1 0.0 1,180 1.2 0.9 2,561 4.9 3,5 1,074 1,5 1,0 2,603 134.5 43.9 2,594 22.3 19,4 2,539 1,6 1,4 1,200 0.8 0.7 All values reportedas < L0D 2,319 4,6 3,2 583 1,4 0,g 2,599 129.7 39,3 2,688 22,7 19,6 2, 329 1.3 1,2 409 0.8 0,6 NA NA NA 2,316 13 0,8 572 0,8 0,5 2,599 27,1 6,9 2,588 3,9 2,6 2,314 0,4 0,3 371 0.3 0.2 2,316 248% 23,9% 572 44,3% 42,0% 2,599 21,0% 16,7% 2,588 17,4% t4,0% 2,314 28,7% 24,9% 371 33.8% 28,6% 2,316 0,2 0,2 572 0,3 0.3 2,599 0~2 0,1 2,588 0.1 0,1 2,314 0,2 0,2 371 0.2 0,2 Tt NA, not applicable; QA, quality assurance. a Se rts in vs ud, ol 1c 4 1 ay Cm a Ch gir *Comparison between matched samples for main test results and blinded, duplicate quelity assurance samples sent to the primary' ~ab, ~Cemparison between matched samples for ee eadGo AY ra Ss 1s main test results and blinded, duplicate q uaFr[y assurance samples sent to the seccnda~ lab. vormeralHed Environmental Health especies Perspectives vue VOLUME 17117 wn121 I NUMBER 12 IDDxec~eenmbbeerr2200069) 1881 22771133..00000099 un soe etal, Fri:sbee et al. Abou th he scr concprtons and dice codpos ac slay Unde sy rbn npcigs C Although the highest serum concentrations of FFOR ware obaved Link Hocking, ndwil bs spor havi. am si Aint of PFOA were observed in Little Hocking, ici rein ht higher burdofeonbesr ST vce it is interesting that higher burdens of other PEC: wee found in other water dice, Conclusion CRA I PFCs were found in other water districts. Icuiguin th aocaton beeen water Th dcfor the 69030 C8 Hkh Prjcs Investigating the association between water PEC concenitions and ern PFC concen. pricpnts provide ville normaton on "2 at}38 mer lcsev PFC concentrations and serum PFC concencations and vegan te dibsof cum PEC fonction, degaphi Sk. Keer bBo Sho On 3s. trations and investigating the distributions of ceupaoal coniions sre beyond he ors incl chm id lfreported daPee Ter occupational contributions are beyond the ope of the praca eps. Fates works ct Ins poplar wih gh para 1R A n scope of the present report. Further work is under ~vay to naodel occupational, temporal, epee ativan ent ift e on e heel Tic spatial, and temporal-spatial variation in water TRC ii fs beeen. bos pouhle alot wir oi Lb 10NuCn l PFC levels, induding differences between pub1c water pps sd privie welb and the be Hu of deo pren cede. Seer co sh hs Fee lic water supplies and private wells and the io wiheun m PFC oc Tn addon, thy provida vale bacline Dara mms association with serum PFC levels. Cormiaions beeen the dic PECs chracisnionof ths opuldn or ih. Amat Ie 18Abie St Correlatiom between the different PFCs wr only modo snd howe dor eqn ro aad ty i tee were generally modest and without discernCo sue. ry he mn Th en therfore, hae th prc eS pt A able age or sex l~atterns. Presently, the meaning of hescoat se ana sd wil 1 prosoh crn snderendoif nhge a hat eert nd ing of these correlations are unclear and will Why ned 1 be smerpreted Ir, with blogs of PEC Gxponrs and i woprce, ieSe HA rdere likdy need to be interpreted later, within he content of betes undenndinofpit. det mong tose (ot sence 0, Be Seon at1. 1 the context of a better understanding of patLe ofcunt sip, soot] of which Gl pods compen fof et netmet on terns of cumulative exposure, environmental accumubion. andphylogic mechosf heCas ilo cmpin 0geocrt ie SSeunn 1o0SeCO accumulation, and physiologic metabolism of he hiieth Hop, Rl beh andexpo or ss heh er ro these chemicals across the life span. Trin tudes as epor anhe com. cs. As moat lr 1 ur das OL BB i Sn Previous studies have reported on the comcy ofPEC detcminstion (un Lesaven 0 an posed population, the C8 Hoth emiet 81.50 fd mdi plexity of PFC determination (van Leeuwen E1000, Ahh mk ron Bolt sidoi aso or oy Pm ra rt 1 et al. 2006). Although intralab measurements Semontoed rwanble sabi. ish Ica elementsfo populons ped |So IroIm demonstrated reasonable stability, interlab meses owed ges Aveefon somo e osm AL Se measurenaents showed larger divergence. It ot sriht carnoem he tes Sot nS Ro Fr is not surprising that measurements from the Pre,whimspencil 700 Roos ha Project, which at times processed > 7,000 sanapicpes anh, would nx shi the ume eso tem ec pies per month, would not achieve the same Io dr edly oi ove rt Chant, SS levd of accuracy as federally funded projects wih lr spl ses and ale ngs ianCoen B Jo r e id with smaller sample sizes and smaller ranges of xponue Spearman ciofnquiglky. JT u ee vigondn io is in 1, PE prs co t,t of exposure. Spearman testing of quality- assurance results demonstrates that rank order ie high proced or ins. and meron. iSR re S dm LN is highly preserved for intra- mad interhboraom - an tory comparisons. ee ine ofthis coho, together Hee Fk 0 temp tice. Seirmninasae T The large size of this cohort, together with the broad rang ofserum PEC value, o Sucmaonlemme a with the broad range of serum PFC values, proves unique opportunfoi veri. be eons cerFl Ie DA ed nO 4 provides unique opportunities for investigatre amocons owen PECs ad hun Bitpipheis Sere mt ing associations between PFCs and human Ri Abbough te proven odydug aera Een ey SOS health. Although the prevalence study design inhlimeitscrause)nfnerlnc,ythe Prof cut rg0krHh eon, He) inherently limits causal inference, the Project mas he rp and boa dy od ph GAS me bc arr remains the largest and broadest study to date of wocaions betwen PFC cxponre and memet s oe on SU Set of associations between PFC exposure and Human hes, Subcohors om hi pope a prs phe human health. Subcohorts from this popuTaio, be followed ovr on, ev ba em So. Fun, Oo sh 15 et 37 Kr i ed Be4r lation, to be followed over time, have been ded sd the C8 Sun Poel bh ict Sn Sont et identified and the C8 Science Panel has dy begun vollment in ongindinl Dee ie already begun enrolhnent in longitudinal Sl Sm SE Sew wT Teen studies. A multivariable analysis of factors tig POR tt ns ptr UE et tS es A ee determining PFOA lords in the population ho be conduc and bmied fr pus SinnPremd has been conducted and subtraitted for pub- Ticaon (Stenland a1. 2009) Addicoml ben Sve enBeh h6 Tome Ti. eh 6 WS, Ge unPK lication (Steenland et al. 2009). Additional geil ams invsigaing ssociatons | pre re targeted analyses investigating associations meen PFCand spo inl chemin marLffori ht between PFCs and specific clinical chemistries and disease endpoints are already under way and will be reported elsewhere. Conclusion The data from the 69,030 C8 Health Project participants provide valuable information on serum PFC concentration, demographic factors, clinical chemistry and stir-reported disease in a population with a high participation rate. Ongoing work investigating the interrehtionships between them will provide dues about possible etiologic relationships, within the limitations of the prevalence study design. In addition, they provide a valuable baseline characterization of this population for subsequent, prospective studies. The results, therefore, have the potential to improve the current understanding of the biology of PFC exposure and are unprecedented anaong toxic tort settlements, most of ~vhich simply provide compensation for the Class without attempting to generate useful health and exposure data or assess health effects. As an innovative effort to gather data on an exposed population, the C8 Health Project can also serve as a modal for future legal settlements for populations exposed involuntarily to environmental contaminants. REFERENCES Apetherg B J, WiRer FR, Herbstman JB, Ca~afat AM, HaMen Needham LL, et al, 2g07. Cord scram cenceot~atians of perftuorooctane suffonete ~PFOS} and perflaorooeta~o- ate 4PFOA} in relation to weight and size at birth. Environ, Health Pers~ect 115:16~t576. CS Health Proie~t 2~9. ~U Dam Hasting WebsRe, Available: htt~://www,hs c,ww,ed u/s om/~ med/~ 8/ [~ccessed 15 October C8 S~e~ce P~neL 2007. Hame oa0e, Available: http~/www, ~Ss~e~eeoeneLo~/[~ccessed 7 Ju~ ~9]. C~]af~t AM, K~kieny~k Z, Re~y JA, Ca~l SP, Tully JS, Need~m LL 2007a. Serum con~e~t~at~o~s fluoma~kyl c~mpou~ds ~ the US population: data from the Nat~o~a~ ~e~Rh a~d ~ut6tion Exa~ina~o~ Survey {~HANES} 199~= E~viro~ Sci Tec~no[ 4117~:~7-~4Z Cafafat AM, Wong LY, Kuktenyi~ L 8ei~y J& Needh~m LL ~ PuM[uoro~l~ ~he~ca]s i~ the O,S, p~[a~n: ~a~ from ~ Nagoya[ Heal~ ~n~ ~utrido~ ~ami~tion S~ey {NHANESJ 200~200~ a~d ~ompa6soas w~th ~HANES t 9~0. E~[roo Hea~th Pe rspe Emmett ~, Shof~r FS, Zhan~ H, Freem~ ~, Desei C, Sh~w LM. 2~6, C0mmuniW expos,urn to ~erfluorooetanoate: reta~onsh~ps betwee~ serum concefltr~t~ons an~ exposure s~urces. J 0~cup En~ron Me# F]aherty JM, Connolty PD, Decker ER~ Kennedy SM, Elle~son ME, Reagan WK, e~ aL 2005= Quantitative ~ete~m~fl~t~un of perf~uoroocta~o~c ~cid i~ sergm and tromet~, J Chmmatogr g AnoM Techno[ Biomed Life ga{verson J~ garner EJ, Ma L ~4. An A~a~ysis of gismo 6t~es a~d Access m Medical C~re in the Ap~a{a~hian 1882 1882 [ET -- VOLUME 117 I NUMBER 12 IDecember 2009 . Envlr~rnental Health Perspectives 22771133..00001100