Document 37Q0d5DbGE7L8vqoNoK6LdBm0

Fg o le ehponlineorg _ AP224-3290 | EHENAVLITRHONMENTAL PERSPECTIVES | i| : Private Drinking Water Wells as a Source of Exposure to PFOA in Communities Surrounding a | Fluoropolymer Production Facility i Kate Hoffman, Thomas F. Webster, Scott M. Bartell, i Marc G. Weisskopf, Tony Fletcher, and Vernica M. Vieira | doi: 10.1289/ehp.1O0n0l2i5n0e34(aOvcatiolbaebrle2a0t1ht0tp://dx.doi.org/) i i i | P&F NB IEHSE 3epareofmvaestnosndHarman Services : p.2 Page 10r21 Piivate Drinking Water Wels as a Source of Exposure to PFOA in Communitis Surrounding a Fhiorogolymer Production Facility KateHoffman'.Thomas F. Webster', Scott M. Barell, Marc G. Weisskopf', Tony Fletcher' and Veronica M. Vieira" "Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts, USA "Program in Public Health, UniversityofCalifornia, Irvine, California, USA "Department of Environmental Health, Environmental and Occupational Medicine and Epidemiology, Harvard School of Public Health, Boston Massachusetts, USA "London School of Hygiene and Tropical Medicine, London, United Kingdom *Corresponding Author: Veronica M. Vieira Viv@bu.edu 715 Albany Steet, Talbot 4W Boston, MA 02118, USA Tel: 617.638.4620 Fax: 617.638.4857 1 p.3 . Page2of27 Acknowledgements: This work is funded by the C8 Class Action Seulement Agreement (Circuit `Court of Wood County, WV. USA) between DuPont and plaintiffs, which resulted from releases ofperfluorooctanoic acid (PFOA, or C8) into drinking water. Funds were administered by the Garden City Group (Melville, NY) that reports to the court. Our rescarch and conclusions are independent of either party to the lawsuit. Competing interests: All authors declare that they have no actual or potential competing interests. Running title: Drinking Water Exposure (0 PFOA Key words: drinking water; pharmacokinetic modeling; perfluorooctanoic acid (PFOA, or C8): private wells; serum List of Abbreviations: C8 - perfluorooctanoic acid, PFOA C1 - confidence interval EPA Environmental Protection Agency GEE - generalized estimating equations IQR -interquartile range. LOQ -limitofquantification MOU - Memorandum of Understanding PFCs - polyfluoroalkyl chemicals PFOA perfluorooctancic acid, C8 2 Ix Page 3of27 Abstract: Background: The C8 Health Project was established in 2005 to collect data on pecflucrooctanoic acid (PFOA, or C8) and human health in Ohio and West Virginia communities contaminated by a fluoropolymer production facility. Objective: We assessed PFOA exposure via contaminated drinking waterin a subset of C8. Health Project participants using private drinking water wells. Methods: Participants provided demographic information, and residential, occupational, and medical histories. Laboratory analyses were conducted to determine scrum PFOA `concentrations. PFOA monitoring data were collected from 2001 to 2005 in 62 private drinking water wells. We examined the relationship between drinking water and serum PFOA levels using robust regression methods. As a comparison to regression models, we used a first-order, single compartment pharmacokinetic model to estimate the secum-to-drinking water concentration ratio at steady-state. Results: The median serum PFOA concentration in 108 study participants using private wells was 75.7 g/L, approxim2a0tteilmeys greater than the US general population levels, but similar 10 local residents drinking public water. Each ug/L increase in drinking water PFOA is associated with an increase in serum concentrations of 141.5 pg/L. (95% confidence interval 134.9-148.1). The serumto-drinking water concentration ratoforthe steady-state pharmacokinetic model is 114. `Conclusions: PFOA contaminated drinking water is asignificant contributor to serum levels in this population. Regression methods and pharmacokinetic modeling produced similar estimates of the relationship 3 p.5 Page dof 27 Introduction: Perfluorooctanoic acid (PFOA,or C8) isa synthetic chemical that s used as a processing. aid in the manufacture of fluoropolymers. Products made with fluoropolymers possess unique abilities including oil, stain, grease, and water repellency. These properties letdo the wide spread use of luoropolymers in a numberofproducts including non-stick cookware, weather and stain resistant clothing and textiles, building and construction materials, and electronics (Rennec 2001). The chemical structure of PFOA makes the compound extcemely resistant to environmental and metabolic degradation. PFOA has been detected globally in the environment (Lau etal. 2007). is well established that PFOA is readily absorbed via inhalation and ingestion. Routes ofexposure in the general population emain unclear, although research Suggests diet is a potentially important source (Trudelct a. 2008). PFOA is detected in the vast majorityofserum samples from the US and world populations (Lau etal. 2007). Once absorbed, PFOA is eliminated from the human body very slowly. Estimates of the serum half-life of PFOA range from 2.3 year in residents of a contaminated community 10 3.8 years in retired. fuorochemical workers (Bartell et al. 2010; Olsen etal. 2007). Although there issome evidence that PFOA concentrations are declining in serum, possibly duc to reductions in use, the median Serum concentrations remain around 4 ug/L in the US population (Calafat et al. 2007s; Calafat et al. 2007; Olsen et al. 2007). PFOA exposure has been linked 10 a variety of health impacts in animals including increased cancer risk, adverse reproductive outcomes, and liver damage (Lau etal. 2007; Lau et al. 2004). Due toa lack of data, health impacts of exposure in humans remain largely unknown (Steenland et al. 2010). a p.6 Page Sof 27 In 2003, the US EPA began an enforceable consent agreement process with industry and other stakeholders to collect additional information for a PFOA risk assessment (US Environmental Protection Agency 2010). The EPA and DuPont (the makerofTeflon) entered a memorandumof understanding (MOU) in November of 2005 as pert of the risk assessment. Building on an agreement in place between the West Virginia Department of Environmental Protection and DuPont, the MOU required DuPtooconndutct environmental sampling. including the monitoring of ground and surface waters around their Washington Works facility in Parkersburg, West Virginia (US Environmental Protection Agency 2004b). DuPont began using PFOA in the manufacture of Teflon at their Washington Works plant in the carly 19505. According (0 data provided by the company, emissions o ai and the Ohio river reached a maximum in the late 19905 (Emmett et a. 2009; Paustenbach et al. 2007). `The company reported a large reduction in these emissions in recent years (US Environmental Protection Agency 2010b). Previous research indicates tha the primary sourceof exposure for individuals in the surrounding communities is contaminated ground water that is used for drinking water (Emmetet al. 2006; Steenlend et al. 2009). The ground water in the area was `contaminated via two main toutes: PFOA released into the atmosphere was deposited onto soils and eventually leached downward into ground water, and PFOA was released directly into the Ohio River which runs near the facility and is linked tothegroundwater supply (Paustenbach ct al. 200). In 2001, a group of residents in communities surrounding the facility fled 2 class-action Tawsuit against DuPont alleging health damages after PFOA was detected in public drinking water distict. The resulting setlement established the C8 Health Project, a baseline survey 5 7 Page sol27 conducted in 2005-2006t investigate potential links between PFOA and human disease in the area surrounding the facility (Frisbee etal. 2009). Previous studies observed a significant association between living in an area with contaminated pubic drinking water and increased serum PFOA levels usingwaterdistrit evel data (Emmett et al 2006; Holzeetar. 2008; Steenlaendt al. 2009;Vieira tal. 2008b). These Studies are partially ecologic in tht the exposure variable is assigned at the group level while other variables ar assigned a the individual level (Webster 2000, 2002; Bjock and Stromberg 2002). In particular, the previous studies provide information on serum concentration i relation t0average exposure for populations serviced by the same water supply, but there is 2 lackof data investigating th relation between private household well contamination and serum levels. In the current analyses, we examine the relationship between serum and drinking water PFOA concentrations using data collected from private drinking water wells contaminated by industrial emissions. By using private well data, we are able 10 quantify PFOA levels in C8 Health Project participants" drinking wateratthe individual level. We asses the relationship using standard regression approaches, nd, for comparison, we also use a pharmacokinetic model to explore the association between PFOA in drinking water and serum levels. Simple, single compartment, first-order models have been applied previously to estimate the serum concentation following exposure from diet and drinking water (Fromme etal. 2007; Vieira et al. 2008b). In the curreat analyses, we utilize updated tims of pharmacokinetic parameters 10 predict the serum todrinking water concentration ratio. We compare the association between drinking water and serum PFOA concentrations from regression models ( those obtained in pharmacokinetic analyses. 6 ps Pageor2r Methods: Sudy Population "The CB Health Project was a cross-sectional study of approximately 69,000 adults `conducted by Brookmar Inc. from August 2005 (0 August2006 (Frisbee et al. 2009). Participants lived in oneofsix public wate districts in West Virginia and Ohio that surround DuPont's Washington Works facility: Belpre, Lite Hocking, Lubeck, Mason County, Pomeroy `and Tuppers Plains-Chester (Figure 1). Data were collected from each participant using questionnaires and clinical examinations obiain demographic information and residential, occupational, and medical histories (Frisbeeetal. 2009). Concentrations of 10 perfluorinated compounds, including PFOA, were aiso determined in serum samples taken once from cach participant between August 2005 and August 2006. Detailed analytic methods were described previously (Kuklenyik et al. 2004). Briefly. serum samples were analyzed using automated solid-phase extraction coupled 10 reversed-phase high-performance liquid chromatography. Participants provided informed consent to have their data used for esearch purposes. Water monitoring was conducted by DuPont in public and private wells surrounding the `Washington Works facility beginning in 2001. Private well monitoring reports contained PFOA measurements as well as the primary use of cach well and the names and addressofcach well's owner. These reports are available through the EPA docket EPA-HQ-OPPT-2004-0113 (US Environmental Protection Agency 2004a). Welinked well monitoring data for 62 private wells used primarily for drinking water to CB Health Project patiipans based on name and address. We also identified family members using well water as individuals having the same last name and address as the well owner fora total of 115 participants. The numofbsameplres taken in * cach well priotro the collection of serum samples varied. Although the majority of wells were 7 po Page oi27 `sampled just once, 11 of the 62 private wells were sampled multiple times... The Institutional Review Board of Boston University Medical Center approved this research. Statistical Analysis In preliminary analyses we identified several participants with serum PFOA concentrations or well PFOA concenteations thatwere much greater than the other participants. For data with outliers, using standard leas squares estimation is both inefficient and biased; regression coefficients arc pulled toward outliers and estimates of the variance are artificially inflated which can obscure outliers (Hampel et al. 1986). As such we used robust regression methods to assess the relationship between serum and drinking water PFOA concentrations. Robust regression provides stable result by limiting the influence of outliers and is generally less subject 0bias than standard least squares estimation methods (Hampel etal. 1986). Robust regressions were performed using Yohia's MM-estimator which possesses high statistical efficiency and provides stable estimates of regression parameters when data include a relatively large percentage of outliers (Yohai 1987). Additionally, because multiple individuals from the same family were included in analyses, which violates the assumption of independence for linear regression, we used generalized estimating equations (GEES) in a second setofanalyses o predict serum PFOA concenraions from drinking water PFOA concentaions. Using GEES, we account fo possible cesidual within-family correlation and investigate the sensitivity of our results from the robust regression that include multiple individuals from the same family in the analyses. GEES and robust regressions were preformed in SAS version 9.1. 8 p.10 Page sof27 `Age and sex have been previously associated with serum PFOA levels in the population surrounding the Washington Works facility as wela in other populations (Emmet et a. 2006; Holzeretal. 2008; Steenland et al. 2009). Additionally. working at the Washington Works plant and growing one's own vegelables were linked o increased PFOA levels in serum (Emmett cal 2006; Steeniand et al. 2009). We included these a priori variables in ll statistical models, A numberofother variables including body weight, bottled water consumption (modeled 2s yes or no). cigarette smoking, and alcohol consumption, which have been previously linked to serum PFOA level, were also assessed (Emmett etal. 2006; Steenland et al. 2009). Only the a priori variables were included in the final models as the others did not materially alter the association between serum and well PFOA levels (did not cause a change greater than 10% in the predicted contributionofdrinking water to serum). For wells with multiple PFOA sampling events, we used the arithmetic average PFOA concentration in each well 10 predict serum levels in regression models. This method provided an estimate of the serum-to-drinking water concentration ratio thati readily comparable to the results of steady-state pharmacokinetic model which assumes that the concentration of PFOA in drinking water is constant over time (discussed in following section). We also performed an analysis using time-weighted water concentrations based on a non-steady state pharmacokinetic model. In main analyses we included all individuals regardlessof how long they hadlivedat their current residence. We also performed analyses investigating the sensitivityofour resulis to the residential duration at a particular well. By restricting the sample to long-term residents (greater than 15 years) we ensure that participants had been exposed to water from a specific well for a period of time long enough fo their serum levels to have reached steady state. 9 pt Page 100127 Pharmacokinetic Models Regression provides us with an estimate of the change in serum concentrations per unit change in water concentration, adjusting forother factors. For comparison with th regression analyses we also predicted the ratoofserum-t0-drinking water PFOA concentration usinag simple first-order, single compartment pharmacokinetic model. Bartel etal. (2010) previously demonstrated that the pharmacokinetics of PFOA in humans are consistent with first-order elimination. Based on data which suggested tha the duration of exposure to PFOA contaminated drinking water in the study population is on the order of decades (Paustenbach et a. 2007), we assumed thalevelsof PFOA in serum had reached a seady.-state concentration. The raio of steady-state serum PFOA concentration. C, (g/L) to water concentration,C.(g/L) was modeled using the following equation (Bartel 2003) wherefis the fraction of PFOA absorbed, Qi the dalywater intake (Liday), kis the first-order tate constant for PFOA elimination (day k=0.693/1 whee tis the half-life), and Vy is the apparent volume of distcibution (L). Values for ach parameter were obtained rom teview of available animal and human PFOA pharmacokinetic data (Table 1). We assumed that 100% of ingested PFOA was absorbed based on animal data (Butenhoeftf al. 2004; Gibson and Johnson 1979: Hundley et al. 2006). Similar estimate of the fraction of PFOA absorbed in humans tha are highly exposed 0 PFOA have been used previously (Thompson etal 2010; Trudel et al. 2008). In previous pharmacokinetic analyses of PFOA (Vieira et al. 2008b), we utilized a serum half-life of 3.8 years (1388 days) based on a small study of retired fluorochemical production workers (Olsen ex 41.2007). Inthe current analyses, we applied & more recent estimate of 2.3 years (#40 days) 10 p12 Page t1of27 based on data from Bartell and colleagues collected in a subsetof C8 Health Project participants (Bartel et al. 2010). The volume ofdistibution (Ve) is proportionality constant in `pharmacokinetic modeling tha relates th total amount of a chemical in the body to the concentration in plasma. We usead Ve for PFOA of 181 ml/kg and 198 mUkg for males and females respectively based on results from cynomolgus monkey experiments (Butenhoff etal. 2004). Thompson etal. proposedasimilar Va (170 ml/kg) using data from residents of two chronically exposed communities around DuPont's Washington Works facility (2010). As the goal ofour regression analysis was to use the scrum and water data o estimate a sicady state atio, and not the Vd, we used the Butenhoffestimate from monkeys i the pharamcokinetic model cather than the Thompson estimate from the same community. We scaled the Vato the sex and body weiogfshtutdy participants and used the median ofthe study population in pharmacokinetic models. Because water consumption data were unavailable, we used the EPA's recommended average tap water intake rate for adults of 1.4 Liday which includes water consumed from the tap as abeverage or used in the preparation of foods and beverages (US Environmental Protection Agency 1997) Results: Linking well monitoring data to C8 Health Project Participants, we were able to identify 115 individuals using 62 different private wells for drinking water. OF these, 4 (3.5%) individuals were missing data (PFOA levels in serum: n = I, body weight: n= 2, race: n= 1). We also excluded vegetarians (n=2) and non-white participants (n=1)a the numbers of cach were 100 small toadequatelycontrolforthse variables. Our final sample consisted of 108 participants. Serum PFOA levels ranged from 0.9to 4751.5 g/L. witah median concentration n p13 Page 120127 0175.7 g/L (mean=171.3 pg/L and standard deviation=499.7 ug/L). As reported previously in the larger C8 Health Project sample (Steenland et al. 2009), individuals growing their own vegetables and employed at DuPont had higher median serum PFOA concentrations (Table 2). PFOA concentrations were higher in older and heavier participants, but differences were not statistically significant (Table 2). `Welllocationsand the corresponding average PFOA concentration are shown in Figure 1. The number of participantsusingeach well ranged from | to 4. The median PFOA `concentration in drinking water wells included in our analyseswas0.2 g/L (mean=0.8 pg/L. and standard deviation=1.9 ug/L), much greater than the US EPA provisional health advisory level of 0.04 ug/L (US Environmental Protection Agency 2009). There was considerable variability between wells, with PFOA concentrations ranging from below the limitof quantification (LOQ=0.006g/L) furthest from the Washington Works facility to 13.3 pg/L closestto the facility. One sample was reported below the limit of quantification and was assigned the LOQ 0.006 g/L in analyses. Multiple samples were taken in 11 wells which were used by 19study participants. In general there did not seem to be an overall trend from 2001 10 2005 in the concentrations of PFOA in private drinking water. Although PFOA concentrations in cach well appeared to fluctuate by season, these differences may be due (0 seasonal changes in precipitation. PFOA concentrations measured in 2004 and 2005 for a subset of wells measured seasonally are shown in Supplemental Material, Figure 1. Regression Results `We examined the shape of the relationship between serum PFOA concentration and average drinking water PFOA concentrationusinga locally weighted regression smoother 2 p14 Page 130127 (LOESS) n S-Plus. Visual inspection of a plot of the smoothed data indicated tha the association between serum and drinking water PFOA levels could be esimated as linear trend (cata nox shown), as suggested by th pharmacokinetic model (equation 1). We therefore included the average drinking water PFOA concentration as a linear predictor of non- transformed serum PFOA concenlrations in regression models. In the adjusted obust regression models each ug/L. increase in drinking water PFOA concentration was associated with a 141.5 g/L. 95% confidence interval (C1) = 1349-148. increase n serum concenteations. Effect estimates for other variables included in the model ar presented in Table 3. Growing one's own vegetables, male gender, and employment at DuPont were associated with elevated serum PFOA levels; however, associations did not reach statistical significance at the 0.05 level, The estimated background serum level in tis population aftr accounting for known sources was 7.4 g/L. (Table 3). Additionally. we investigated differences inthe serum-to-drinking water concentration ato in males and females. Staifying by sex we observed very similar ratios in both sexcs. Accordingly, including an interaction term in models,wedid not observe a significant (p-value<0.05) sex by water concentration interaction (data not shown). Robust regression analyses revealed 6 outliers (observations for whichth standardized residual was larger than thee). For thes individual, the predicted values for serum PFOA concentrations using regression parameters undero over estimated observed concentrations (standardized residuals 3.0 0.44.5). In analyses using GEE, we observed a small withinfamilies correlation ofserum PFOA levels of 0.1. Compared to results ofthe robust regression. `GEE analyses excluding outliers produced a very similar estimate of effect 5) for each pg/L increase in drinking water PFOA concentration (3=141.8 pg/L; 95% C1 = 134.3-149.4. When outliers were included in the GEE, the estimate of the association between serum and drinking, 3 p15 . Page 140127 water PFOA levels was much larger. The inclusionofone participant i particular, with the highest serum and drinking water PFOA concentrations in the population, increased the estimate ofeffect 0 232.7 pg/L (95% CI=200.9-264.5). We could not identify a plausible explanation for hisparticipant's exteme serum concentration using available data (the participant did not report being employed in the fluorochemical industry). Increased water consumption in this individual may have resulted in the extreme concentration, however data were not available to evaluate this hypothesis. When we restricted to individuals witha residency duration greater than 15 years results were similar (=140.2 ug/L; 95% CI = 132.1-148.4;1=67). We considered other residential duration restrictions (2; 5, 10, nd 20 years), but restrictions had lite effect on the magnitude of the association between serum and drinking water. We also excluded participants who were ever employed at the Washington Works facility,a these individuals may have had other significant Sourcesof exposure. Again, the association between drinking water levels and serum was similar when these individuals were excluded. Additionally, excluding participants who reported consuming bottled water (N=6) from analyses had lite effect on the magnitude of the association between serum and drinking water. Comparisonof Pharmacokinetic and Regression Results Using the simple steady-state first-order pharmacokinetic model (equation 1) with a medianVd of 15.000 mL in the study population afer scaling for the body weight and sex of study participants, we obtained serum-to-drinking water concentration ratio of 114. This is similar 0 the estimate derived from regressing serum concentcations vs. water concentrations, 1415. u p16 Page ts of27 Discussion: `Serum PFOA concentrations in private well users in theareasurrounding DuPont's `Washington Works facility were much greater than those observed in the general US population end were comparable to what has been observed in the study arca previously (Emmett ct a. 2006: Steenlaendtal. 2009; Vieira etal. 20080). Private drinking water wells in the area were. contaminated with PFOA, with levels in some wells being much greater than those observed in public drinking water supplies in the same arca which ranged from 0.03 jig/L. in Mason County 103.5 ug/L in Litle Hocking (Bmmet et al. 2006; Steenland et al. 2009). Using private well data, we had a large number of individual exposure levels and were able to assess a wide range ofexposurteso PFOA via drinking water. Results of regression analyses are consistent with strong association between serum PFOA levels and drinking water PFOA concentrations. There was litle difference in the association between serum and drinking water PFOA concentration when we limited analyses to ' 67 individuals that were long-term residents. "The serum-to-drinking water concentration ato of 141.5 estimated using regression was similar to atios obtained in previous partially ecologic analyses. In our previous work in the study area we found serum-to-drinking water concentration ratios in public water districts ranging from 59 to 411 (Vicira ct a. 2008a). In Little Hocking, Ohio, near the Washington `Works facility,Emmettand colleagues estimated a water concentration rato of 105 in an analysis of public water consumers (Emmet et al. 2006). Additionally, in a small sample of private wel users (n=6), serum to water concentration ratios ranged from 142 to 855 (Emmett et al. 2006). 15 pA? Page 16.027 The steady-state serum-to-drinking water concentration atio of 114 obiained from pharmacokinetic modeling was closeto the estimate ofeffect (141.5) obtained from regression analyses, suggesting that the pharmacokinetic miodel provides a reasonable estimate. We used a serum PFOAhal life based on data that Bartell and colleagues collected ina subset of C3 Health Project participants with exposure levels and patternssimilarto the participants in these. analyses (Bartel et al. 2010). Using the half-life estimate from Olsen et a. (2007) of 3.8 years increased the serum-to-drinking water rato 10 183. Other pharmacokinetic parameters that we used were more uncertain, particularly the volume of distribution which was estimated based on animal data (Butenhoeftf al. 2004). A recent study by Thompson et al. estimated a very similar Vid (170 mike) based on data from community residents (2010). Using the Va from Thompson produced a similar scrum-to-drinking water concentration ratio of 126. Based on data from subchronic monkey studies however, Washburn t al. (2005) recommend the use of a volume of distribution a factor of 10 highec than the Butenhoff et a. ratio that we used in analyses (Butenhoff et al. 2004); using this ratio would have reduced our ratio by an order of magitude. Further research is needed on the volume of distribution of PFCs in humans. Additionally, in the absence of consumption data for cach individusl, we used the EPA estimated average daily tap water consumption value of 1.4 Liday; however, water consumplion in th study population likely varies (US Environmental Protection Agency 1997). We believe thattdhifference in serum-to-drinking water concentration ratio estimates rom regression and pharmacokinetic `models may be explained by these uncertainties. As reported previously for C8 Health Project participants, we observed a positive association between serum PFOA levels and growing one's own vegetables afer adjusting for water concentration suggesting consuming locally-grown food may be an important source of 16 p18 Page 17 of 27 `exposure in this population (Steenland et al. 2009, Bartell et al. 2010). The background serum PFOA concentration predicted in regression analyses (7.4 pg/L) is greater than background levels previously reported in the US population (geomelric mean 3.8 ig/L (Calafat etal. 2007b); arithmetic mean 4.3 g/L (Centers for Disease Control and Prevention, 2007). These results suggest that there may be other sources of PFOA exposure intheC8 Health Project population that were not included in the model or that random exposure misclassification may be inflating the predicted background levels fo this population. Other potentially important sources of PFOA exposure in this population include water consumption at work, school, or religious and social organizations frequented by study pastiipants. Although the release of PFOA from the `Washington Works facility has been reduced (US Environmental Protection Agency 2010b), PFOA may sill be present in indoor environments and may contribute an additonal source of exposure for residents. Data were not available 10 test hypotheses on these exposure sources. Our analyses ar limited by our steady:state assumption and reliance on a single `measurement of serum levels and, in most case, a ingle measurement of drinking water PFOA levels.For a small numberofindividuals with multiple well measurements, we considered variability in well measurements in a sensitivity analysis usinag time weighted well concentration rather than an arithmetic average to predict serum PFOA concentrations (see Supplemental Material). Although there was some seasonal variability from 2001 0.2005,on average well PFOA concenteations were fairly stable, and there was no long-term trend during this time period. Consequently, predicted serum concentrations that accounted for variation in PFOA concentrations in wellswere similar 0 those oblzined using simple steady-state models (data not shown). v7 p19 Page tgorz Despite these limitations, our analyses have a numbeorf strengths. We were able to link drinking water PFOA measurements oa relatively large number of individual study participants consuming private well water. The extensive questionnaire administered as part of the C8 Health Project allowed us to considera number of potential confounders in the association between serum and drinking water PFOA levels (including age, sex, growing one's own Vegetables. body weight, bottled water consumption, cigarette smoking, and alcohol consumption). Unlike previous assessments which used water-district-level water samples, participants drinking water well measurements were used, increasing te variability ofexposure. measures. Additionally, available residential history information allowedustoconsider differences in long and short term residents using contaminated wells for drinking water. Conclusions: Private drinking water wells in West Vicginia and Ohio communities surrounding the `DuPont Washington Works facility are contaminated with PFOA. Concentrations in private wells are, in some cases, much greater than those observed in area public water istrict. For private well users, adjusted regression analyses indicate that PFOA levels in drinkingwaterarc a significant predictor of serum levels. The regression analysis predictead 141.5 ug/L increase in serum levels for cach pg/L increase in drinking water PFOA, very simitlotahre 114 pg/L in serumfor cach gL. predicted in steady-state pharmacokinetic models, These results may also be applicable in other arcas with point-source PFOA contamination 18 p.20 Page 190127 References: Bartell $. 2003. Statistical methods for non-steady state exposure inference using biomarkers. [PhD Dissertation]. Davis, CA: University of California, Davis. Bartell SM, Calafat AM, Lyu C, Kato K, Ryan PB and Steenland K. 2010. Rateofdecline in secum PFOA concentrations aftr granular activated carbon filtation at two public water s1y0s.t1e2m8s9/ienhpO.h0i9o01a2n5d2.We[sOtnVliirgn4ieniFae.bErnuvairryo2n01H0e)a.lth Perspect 118(2): 222-228; doi Bjork J, and Stromberg U. 2002. Effectsofsystematic exposure assessment exrors in partially `ecologic case-control studics. Int J. Epidem 31: 154-160. `Buteahoff JL, Kennedy GL, Jr, Hinderliter PM, Lieder PH, Jung R. Hansen KJ, etal. 2004. 4P0h6a.rmacokinetics of perfluorooctanoate in cynomolgus monkeys. Toxicol Sci 82(2): 394 CalafatcAoMnc.enKturkalteionnysikofZ,11RepioldyyflJuAo,rCoaauldkiylllcSoPm,pTouulnldysJSinatnhde UN.eSe. dphoapmulaLtLi.on2:00d7a2t.a Sferromumthe national health 231-242. and nutcition examination survey (NHANES). Environ Sci Technol 41(7): CalafatcAhMem,icWaolnsginLtYh,e KU.uSk.lepnoypuilkatZioRne:iddaytaJAfraonmdtNheeeNadthiaomnalLL.Hea2l0t0h7ba.ndPoNluytfrliutoiroonalkyl EEnxvaimrionnatHieoanltShuPrevresype(cNtH1A1N5(E1S1)):21050936--21060024.and comparisons with NHANES 1999-2000. Centers for Disease Control and Prevention. 2007. National Health and Nurtition Examination Shuuruvpeyi:iw2w0w0c3d-c2.0g0o4viLnacbhosr/aathoarnyeFsi/lnesh.anAveasi2l0a0b3le-:2004/1ab03_04 hum [accessed 16 August 2010] EmmettexEpAo,suSrheotro pFeSr,luZohraonocgtHa,noFartee:emraenlatDi,onDsehsiapisCabentwdeeSnhsaewruLmM.co2n0c0e6n.lraCtoimomnsunaintdyexposure sources. J Occup EnvironMed 48(8): 759-770. FrisbeehSeJa,ltBhroprookjsecAt:P,deJsri.gnM.ahmeetrhAo,dsF,laenndsbpoarrgtiPc,ipAanmtos.ldEnSv.iFrloentcHheearlTt,h ePtearls.pe2c0t09.117T(h1e2)C;818731882. FrommeadHu,ltSpcohpluulamtmieorn Mto,pMeorflllueorriAn,atGerdusbuebrstL,anWcoeslzusGi,ngUdnugpelwiicastseJd,ieettaplo.r2t0i0o7n.s eEnxdposure of an biomonitoring data. Environ Sci Technol41(22): 7928-7933, Gibson $ and Johnson J. Laboratories, nc. 1S9u7b9s.idAibasroyrpotfi3onMofCFomCp-an1y4.3S-t14PCaulin, ras MN. afAtR-ea2r2i6n.g04l5e5o,ral dose. Riker 19 p21 Page 20 of 27 Hampel`AFpRp,roRaocnhchBetatsiedEMon, IRnofulsuesnecceuFwunPcJt,ioannsd. SNtaehwelYWoArk.: 1W9i8l6e.y.Robust Statistics: The HolzeJrp,erMfilduaosricnhatOe,d RcaoumcphofuunsdssK.i,nKcrhaifltdMre.nRaenudpeardtultRs, eAxnpgoesreedrJtocpterafl.lu2o0r0o8.octBainoomaotne-itoring of `contaminated drinking water. Environ Health Perspect 116(5): 651-657. Hundley"aSmGm,oSnairruimfpAeMcflaunordooKceinanneoadtyeG(LA.PF20O0)6.afAtbesoorrapltaidomni,ndiissttreabtuitoinont,oavnadrieoxucsrestpiecoineso.f Drug ChemToxicol 29(2): 137-145. Kukleny`iekxtrZa,ctRieoincahnJdAm,eTauslulryeJmSe,nNteoefdphearfmluLoLrianantdedCaolragfaantiAcMa.cid2s00a4n.d Aaumtiodmeastiendhsuomlaidn-pshearsuem `and milk. Environ Sci Technol 38(13): 3698-3704. Lau C, AtneivtioelweoKf,mHoonditeosriCn,gLaanidD,toxPifcaohlloegsi-cHaultfcihnednisngAs. aTnodxiSceoledSJc.i29090(72.):Pe3r6f6l-u3o9r4o.alkyl acids: & Lau C, BanudttehneihrodJferLfivaantidveRso.gTeorxsiJcMo.l 2A0p0p4l. PThhaermdaecvoello1p9m8e(n2t)a:l23to1x-i2c4i1ty of perluoroalkyl acids Olsen GPpWer,reflliMumaoiirnroaorDcyCtea,nvaRiadeteaengce(enPoFfWOaKdA,e)cEclloilnnccfeesnoitnnrapMteirEofnlsuEohirrnoeAoscmtmeaarnniecsDauJln,foRBneuatdteeCarh(ooPsfFsfOJbSLl),oaocndtdadlo.no2r0s0.7. Chemosphere 68(1): 105-111 Pausten`bhaucmhanDJe,xpPoasnukroeJtMo,peSrcfoltutoProKocatnadnoUinciacceidKM(P.FO2A00)7:.arAetmreotspheocdtoilveogyexfpoorseusrteimaastsiensgsment. of acommunity (1951-2003). J Toxicol Environ Health A 70(1): 28-57. Rennec R15240A0-11.60GAr.owing concern over pefluorinated chemicals. Environ Sci Technol 35(7): SteenlanledveKl,sJiinnaCc,oMmamcuNneiitlyJ,SuLraroyunCd.inDgucacahtemmaincaAl. Vpliaenitr.aEVn,vietroanl.H2e0a0l9.thPPreerdsipcetcotrs1o17f0P7)F:OA 1083-1088. Steenlapdne0drifK:l.1u0Fo.r1lo2eo8tc9tc/achnheTopri,0c9Saa0cv1ii8dt2z(7P.DFAO.A)2.010E.nvEipriodnemHeiaolltohgiPceresvpiedcetnc1e18o8n):the health ffects of ThompspaochniadrJm,aanLcdoorkpbieenrreftlMiu,corTmoooocdmtesalniLenMgs,utlKofaocnthioacraaKcc.itCdear.liaEzfneavetixrApoonMsuInratend3o6f(M4uA)eu:lslt3er9ra0l-Ji3Fa.9n7s2;0t1o0p.erUfsleuoofrooscitmapnloeic d0i:10.1016j envint 2010.02.008 [Online 20 March 2010]. 20 p22 Page21 of 27 "Tiudel EDs,tHiomraotiwnigtzcoLn,sWuomremruetxhpoMs,urSechloerPiFngOeSraMn,dCPoFuOsAi.nsRIiTskanAdnaHlun2g8e(r2)b:ub2i5e1r-2K6.9.2008. US EnviErnovnimreonntmaelntParlotPercottieocntiAognenAcgye.nc1y9.97W.asEhxipnogstuorne.FDacCt,orEsPAH/aGnOdObIoPo-k95(/Fi0n0a2lFRaecp.ort), US. US EnviernovnimreonnmteanltParlotaescsteisosnmAegnetnactyW.as2h0i04nag.toDnu,PWoensttPVFirOgAinsiiate-ErePlAa-teHdQm-oOnPiPtoTr-i2n0g0a4n-d0113 US EnviErnovnimreonntmaelntParlotPercottieocntiAognenAcgye.nc20y0a4bn.d EM.eIm.oDruaPnondtumDeofNuenmdoeurrstsanadnidnCgobmeptwaeneyn fthoearUS Perfluorooctanoic acid (PFOA) HQ-OPPT-2004-0113.0002. ite-related environmental assessment program. EPA- US Enviarciodnm(ePnFtaOlA)PraontdecpteirofnlAugoernococyt.an2e00s9u.lfPornoavties(iPonOaSl)h.ealEtPhAa-dHvQi-soOrWi-e2s0f0o7r-p1e1rf8l9u-o0r1oo8c3t,anic. US Envitreolnommeernst:aElnPfroortceecatbiloen Acognesnecnyt. a2g0r1e0eam.enPter(fEluCoAr)oopcrtoacneosise taocigden(ePrFatOeAa)ddaintdiofnlaulorinated iAnufgoursmatti2o0n10.].Available: htp://www. cpa. govioppintr/pfowpubseca html {accessed 16 US Envi"Treolnommeernst:al2P0r0o9teacntniuoanlApgreongcrye.ss2r0e1p0obr.ts.PeArvfaliuloarboloec:tanoic Acid (PFOA) and Fluorinated hupi/svww.cpa.govioppintploalpubsistewardshippreports3 August 2010]. himl#2008. [accessed 16 Vieira Vh,eaWletbhssiteurdiTe,s:BaErxtpeolsu5,reStveieandlrainndkiKn,gSwaavtietrz cDonatnadmiFnlaettecdhbeTyr.a2T0e0f8lso.nPmFanOuAfaccotmurmiunngity Pfaoclilliuttya.ntDsi(oPxOiPns2)0,0B8i-rm28itnhghIantmerEnnagtlioannadl SUKy.mposium on Halogenated Persistent Organic Vieira Vh,eaWletbhsstteurdiTes.:BEaxrptoeslu5r,eSvtieacdnrliannkdiKn.g, wSaavtietrzcDonatnadmiFnlaetetdchbeyTr.aT2e0f0l8on. mPaFnuOfAacctoumrmiungnity facility. Organohalogen Compounds 70 730-732. `WashbuErxnpoSsTu,rBeiansgsmeasnsmTeSn,t BarnaditrhiwskaicthearSaKc,teBriuzcaktiRonC,forBupxetroflnuLorWo,ocCtlaenwoeatlel iHnJ,seeltecalt.ed2005 `consumer articles. Environ Sci Technol 39: 3904-3910. `WebsterTF. MA: 2B0o0s0t.onBiUanisveinrscictoy.logic and semi-individual studies. [PhD Dissertation]. Boston. `WebsterI,ntTeFm.a2t0i0on2a.lCJoomumrenanltaorfyE:pDiodeemsiotlheogsype3c1t:r1eo61f-1ec6o2l.ogic bias haunt epidemiology? 2 p.23 Pago 22.0127 `Yohai VJ. 1987. High breakdown-point and high efficiency robust estimates for regression. Aan Statist 15(2): 642-656. 2 p2 Page 230127 Table 1: Pharmacokinetic parameter values and sources. Parameter Symbol Value Data Source WaFtearinctoafketPFOiA abosorbned" Half-life Volumeofdisuibution* 0 11040U%day UGS EiPAaInb9d9J7oshnsoon19n79 wh 82430ydeaayrss. Vd male18imikg Barell etal. 2010 Buteohoffetal.2004 Fmeumlatliepl1i9b8eydmig, individual body weight * based on animal data 2 p.25 Page 260127 `(Teanbeldeia2n: Sseelreucmtecdonpcoepnutlraattiioonncahnardacitnetreirsqtuiacrsti(lenurmanbgeer ((I%Q)R)),)s,earnudmsPtaFtiOstAiccalonsciegnntirfaitciaonncse (ofg/L) difference (p-value). CrTaortaacltPeorpiusltaitcion FeMmalaele Grow own vegetables NYeos Employed at DuPont No Age Yes =<65 Years Body We>i6g5htYears =<80kg >80kg N1@08(100%) S57L(@5I223%%)) 6E4(T59E3%)) M14E(I1O30%%)) 6A3S(E8T3%%)) 5S08((4S6337%%)) M75e.d7iaunglslerGu1m5-P1F3O0A5)(IQR) ~~ p-value 868.21 2uggL@(1405-91-116S433)) 010 9S10T2uggl ((254790--11047532)) <0001 876.I7n.g6lL4@(7142-21-4150.214)) oi 5B9489pugg(20(6@9-.01-114559.1)) 035 683512ugg (G3O115--117077.74)) 064 2 p.26 Page 25 of 27 Tible 3: Adjusted robust regression model of serum PFOA pg/L. Covariate: Bea s% Cy Intercept Well PFOA ug/L. 714415 AMgaeles>65Years 188 42 EGmrpolwoyOewdnatVeDguePtoanbltes 18.4 59 ((193489110024144)88.1) (126412013091.519)) (1234013108316)2) a*Tnhdealicnochloulsicoonnosfumopthteironc)ovdairdiantoetsa(lbteordythweemigahitn,absostotclieadtiwoants.er consumption, cigarette smoking. 2 p.27 Page 26.027 Figure Legend: Figure 1: Water districts included in the C8 Health Project and the locations of private drinking. water wells. The average PFOA concentration (ug/L) in each private well is shown. 2 . p28 Pagerrorzr fms N: a : | LittSle HTocking Bre CS abe TpesPlans --Y "gf <* Mason onan PrivateWells. 2bitre ie 2tuz79mm (500x500) p.29 Supplemental Material Private Drinking Water Wels as a Source of Exposure 0 PFOA in Commuaites Surrounding a Fluoropolymer Production Facility KateHoffian',Thomas F. Webster', Scott M. Bartell', Marc G. Weisskopf', Tony Fletcher and Vernica M. Vieira! `Department of Environmental Health, Boston University SchoolofPublic Health, Boston, Massachusers, USA "Program in Public Health, UniversityofCalifornia, vine, California, USA Departmentof Environmental Health, Environmental and Occupational Medicine and Epidemiology, Harvard Schoolof Public Health, Boston Massachusetts, USA "London SchofoHygoielne and Tropical Medicine, London, United Kingdom 1 p30 TaofbConltenets: Supplemental Material, FIEUIE 1... Non-StaStePtharemacoakindedcys...... References... SE Page3 i POO4 Pages 2 PE g | %i.g i BE (I | t1d5i+2s iE 28% yi g | z 15 FEE / T1 y|z|se3eftf | 3HEL3:Et 1T33E31T1 326 lest 2 Sede 2 2f2: 2t ii o|E(gsoeess ii isE2i3gs8 H E Te eo r=;i 3(R8i4i2s Vode ESES p32 `The time-weighted water concentration C_ computed using the weights a, is given by: C.=Xac, 6) "The weight during each time point i give by. o== ( ((--e mOyR) " We included the time weighted PFOA concentration in well in regression models based on these. equations. PFOA concenirations in each well varied by season, bu in general there did not scem bea long-emm rend from 2001 to 2005 in the concentrations in cach well; the arithmetic and time-weighted concentrations were very similar. Consequently, using ether method produced a similar estimateof the atioofserum to drinking water PFOA concentrations. References: Bartell S[. P2D00D3i.ssSetrattaitstiiocna]l. mDeatvhiosd,sCAfo:r nUnoinv-esrtseiatdyyofstaCtaeliefxopromsiuar,eDaivnifse.rence using biomarkers. :d0 ON SNIVINOO 5 . p33 Nonatendae pharcinetio For pricon ive wl ith PFO lestha ried vr te,stay.site mdels ca provid cust tesof sn PFOA levels Alegh ataohechanges PFOA concentrations over time were not collected in all wells, multiple measurements of PFOA were taken in 11 wells during the study period. We therefore performed another regression onde in ewe welcncaeaeiionmest vergesbefor). The im-wegtedcocanrtion wsdriv hestadsemel ive byorl 2003): CTO = $10C,et (my ) hae on where es PROAacento me, Qsi ly wer nk 0, Co's concn ofPRON rst iin wt in ieperioGit). she ith prt han of fsuion fraction of PFOA absorbed, k is the first-order rate constant for PFOA elimination (day), and , Bringing the constants out from within the summation, equation 1 the blood concentration (C,) is given 2s functionofthe constants / . k and ) and the time-weighted water concentration ( c=wn, 5 .ac,, - Le @ .