Search

Background: The C8 Science Panel was composed of three epidemiologists charged with studying the possible health effects of PFOA in a highly exposed population in the mid-Ohio Valley. The Panel determined in 2012 there was a 'probable link' (i.e., more probable than not based on the weight of the available scientific evidence) between PFOA and high cholesterol, thyroid disease, kidney and testicular cancer, pregnancy-induced hypertension, and ulcerative colitis., Objective: Here, former C8 Science Panel members and collaborators comment on the PFOA literature regarding thyroid disorders, cancer, immune and auto-immune disorders, liver disease, hypercholesterolemia, reproductive outcomes, neurotoxicity, and kidney disease. We also discuss developments regarding fate and transport, and pharmacokinetic models, and discuss causality assessment in cross-sectional associations among low-exposed populations., Discussion: For cancer, the epidemiologic evidence remains supportive but not definitive for kidney and testicular cancers. There is consistent evidence of a positive association between PFOA and cholesterol, but no evidence of an association with heart disease. There is evidence for an association with ulcerative colitis, but not for other auto-immune diseases. There is good evidence that PFOA is associated with immune response, but uneven evidence for an association with infectious disease. The evidence for an association between PFOA and thyroid and kidney disease is suggestive but uneven. There is evidence of an association with liver enzymes, but not with liver disease. There is little evidence of an association with neurotoxicity. Suggested reductions in birthweight may be due to reverse causality and/or confounding. Fate and transport models and pharmacokinetic models remain central to estimating past exposure for new cohorts, but are difficult to develop without good historical data on emissions of PFOA into the environment., Conclusion: Overall, the epidemiologic evidence remains limited. For a few outcomes there has been some replication of our earlier findings. More longitudinal research is needed in large populations with large exposure contrasts. Additional cross-sectional studies of low exposed populations may be less informative., (Copyright © 2020. Published by Elsevier Ltd.)

Introduction: PFOA (perfluoroctanoic acid) is a perfluoroalkyl substance (PFAS). Although use in the US has been phased out, PFOA persists indefinitely in the environment, and is present in the serum of virtually all people in industrialized countries. Approximately 6 million Americans drink water comtaminated with PFOA above EPA-recommended levels. In a previous cohort study (n = 32,000), we found a strong positive exposure-response relation between PFOA serum levels and subsequent ulcerative colitis (UC) in a high-exposed population from the mid-Ohio valley, but no association with Crohn's disease. In the present study we aimed to determine if UC cases had higher levels of PFOA than did controls or Crohn's disease patients., Methods: We measured PFOA and three other PFAS in the serum of 114 UC patients, 60 Crohn's disease patients, and 75 controls, within a year of diagnosis. We conducted regression analyses to assess the association of the PFAS with diagnosis., Results: The mean age of subjects was 17 years. The mean year of diagnosis was 2007. Mean levels of PFAS were similar to US levels. Mean log PFOA level in UC patients was 38% higher (p = 0.01) than the combined group of Crohn's disease and controls. In contrast, the three other PFASs were significantly higher in controls and Crohn's patients than UC patients. The odds ratio for UC per one unit of log PFOA was 1.60 (95% CI 1.14-2.24), but the trend by quintiles was not monotonic (1, 0.84, 40.98, 33.36, 2.86)., Conclusion: We found higher serum PFOA in UC cases compared to Crohn's disease patients or controls, in contrast to other PFAS. Our research is limited by not knowing if the elevated PFOA preceded UC in this population., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Perfluorooctanoic acid (PFOA), a suspected endocrine disruptor, is a bio-persistent chemical found at low levels in the serum of nearly all U.S. residents. Early menopause has been positively associated with serum PFOA in prior cross-sectional studies., Methods: We conducted a longitudinal analysis of age at menopause among women, aged ≥40 years, (N=8759) in a Mid-Ohio Valley community cohort, exposed to high PFOA levels via contaminated drinking water. Using estimated retrospective year-specific serum PFOA concentrations (1951-2011), we examined the associations between PFOA, as cumulative exposure or year-specific serum estimates, and natural menopause using a Cox proportional hazards models. As participants were initially recruited in 2005-2006, we also analyzed the cohort prospectively (i.e., from the time of enrollment), using both modeled cumulative PFOA, and PFOA serum levels measured in 2005-2006. Women with hysterectomy (a competing risk) were either censored or excluded from the analysis., Results: Neither in the retrospective nor the prospective cohort did we find a significant (at α=0.05) trend between PFOA exposure and natural menopause. The non-significant, hazard ratios by quintile of increasing cumulative serum PFOA were 1.00 (referent), 1.00, 1.09, 1.05 and 1.06 (trend test for log cumulative exposure: p=0.37) with hysterectomies censored, and 1.00 (referent), 1.06, 1.13, 1.09 and 1.11 (trend test for log cumulative exposure: p=0.85) with hysterectomies excluded. Year-specific serum estimates were also not associated with early menopause., Conclusion: Our data suggest that earlier age at menopause is not associated with PFOA exposure., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Perfluorooctanoic acid (PFOA) was released from a mid-Ohio River Valley chemical plant, exposing the surrounding community to PFOA for >50 years, primarily through drinking water. Toxicological studies and some previous human studies have suggested that PFOA can disrupt thyroid homeostasis. We examined the association between PFOA and thyroid disease among community members and plant workers., Methods: Participants completed health surveys during 2008-2011. Yearly serum PFOA concentrations were estimated for each participant starting at birth or in 1952, whichever came later. We used Cox proportional hazard models, stratified by birth year, to assess adult thyroid disease hazard in relation to time-varying yearly or cumulative (sum of yearly estimates) estimated PFOA serum concentration, controlling for sex, race, education, smoking, and alcohol use., Results: Of 32,254 participants, 3,633 reported functional thyroid disease (excluding neoplasms, congenital disease, nodules without functional changes, cysts, and unspecified type). Analyses were restricted to 2109 cases of functional thyroid disease with thyroid prescription medication use and validation through medical record review. In analyses starting at age 20 years or in 1952, thyroid disease hazard ratios across cumulative exposure quintiles were 1.00, 1.24, 1.27, 1.36, and 1.37 among women and 1.00, 1.12, 0.83, 1.01, and 1.05 among men (log-linear trend tests: P = 0.03 and P = 0.85, respectively); similar results were observed for yearly exposure. Associations were observed for hyperthyroidism and hypothyroidism among women. Some subanalyses also suggested an increased hazard of hypothyroidism among men., Conclusions: Higher PFOA exposure was associated with incident functional thyroid disease in this large cohort with high exposure.

Background: A cohort of community residents and workers is the basis for a series of epidemiologic studies of a Mid-Ohio Valley population with substantial perfluorooctanoic acid (PFOA) exposure due to releases from a chemical plant., Objectives: We describe study design, methods, and study participants for a longitudinal cohort study of associations between PFOA exposure and adult chronic diseases., Methods: Two cohorts were formed, one recruited from community residents who participated in a previous community-wide survey, and one from plant workers. Study participants were interviewed during 2008-2011 regarding demographics, health-related behaviors, and personal history of chronic diseases. Reported diseases were validated through medical records review and registry matching. Here we describe cohort characteristics, compare survey respondents and nonrespondents, provide data on the number of diseases reported and validated, and describe historical estimates of serum PFOA concentrations over time., Results: The final combined cohort included 32,254 participants (28,541 community; 3,713 worker). Participation rates were high (community, 81.5%; worker, 72.9% of target population). The final population from each cohort was representative of the target population in terms of demographic characteristics and measured serum PFOA concentrations in 2005-2006. The study had a wide exposure range and the number of reported cases of chronic diseases was high, resulting in greater power to detect associations than has been the case for many previous studies., Conclusions: This is the largest study to date of the health effects of PFOA. The information from this cohort is being used to examine associations between PFOA exposure and multiple adult chronic diseases.

Background: Little is known about environmental determinants of autoimmune diseases., Objectives: We studied autoimmune diseases in relation to level of exposure to perfluorooctanoic acid (PFOA), which was introduced in the late 1940s and is now ubiquitous in the serum of residents of industrialized countries., Methods: In 2008-2011 we interviewed 32,254 U.S. adults with high serum PFOA serum levels (median, 28 ng/mL) associated with drinking contaminated water near a chemical plant. Disease history was assessed retrospectively from 1952 or birth (if later than 1952) until interview. Self-reported history of autoimmune disease was validated via medical records. Cumulative exposure to PFOA was derived from estimates of annual mean serum PFOA levels during follow-up, which were based on plant emissions, residential and work history, and a fate-transport model. Cox regression models were used to estimate associations between quartiles of cumulative PFOA serum levels and the incidence of autoimmune diseases with ≥ 50 validated cases, including ulcerative colitis (n = 151), Crohn's disease (n = 96), rheumatoid arthritis (n = 346), insulin-dependent diabetes (presumed to be type 1) (n = 160), lupus (n = 75), and multiple sclerosis (n = 98)., Results: The incidence of ulcerative colitis was significantly increased in association with PFOA exposure, with adjusted rate ratios by quartile of exposure of 1.00 (referent), 1.76 (95% CI: 1.04, 2.99), 2.63 (95% CI: 1.56, 4.43), and 2.86 (95% CI: 1.65, 4.96) (ptrend < 0.0001). A prospective analysis of ulcerative colitis diagnosed after the baseline 2005-2006 survey (n = 29 cases) suggested a positive but non-monotonic trend (ptrend = 0.21)., Discussion: To our knowledge, this is the first study of associations between this common environmental exposure and autoimmune diseases in humans. We found evidence that PFOA is associated with ulcerative colitis.

Background: People living or working in eastern Ohio and western West Virginia have been exposed to perfluorooctanoic acid (PFOA) released by DuPont Washington Works facilities., Objectives: Our objective was to estimate historical PFOA exposures and serum concentrations experienced by 45,276 non-occupationally exposed participants in the C8 Health Project who consented to share their residential histories and a 2005-2006 serum PFOA measurement., Methods: We estimated annual PFOA exposure rates for each individual based on predicted calibrated water concentrations and predicted air concentrations using an environmental fate and transport model, individual residential histories, and maps of public water supply networks. We coupled individual exposure estimates with a one-compartment absorption, distribution, metabolism, and excretion (ADME) model to estimate time-dependent serum concentrations., Results: For all participants (n = 45,276), predicted and observed median serum concentrations in 2005-2006 are 14.2 and 24.3 ppb, respectively [Spearman's rank correlation coefficient (r(s)) = 0.67]. For participants who provided daily public well water consumption rate and who had the same residence and workplace in one of six municipal water districts for 5 years before the serum sample (n = 1,074), predicted and observed median serum concentrations in 2005-2006 are 32.2 and 40.0 ppb, respectively (r(s) = 0.82)., Conclusions: Serum PFOA concentrations predicted by linked exposure and ADME models correlated well with observed 2005-2006 human serum concentrations for C8 Health Project participants. These individualized retrospective exposure and serum estimates are being used in a variety of epidemiologic studies being conducted in this region.

Perfluorooctanoic acid (PFOA) has been detected in environmental samples in Ohio and West Virginia near the Washington Works Plant in Parkersburg, West Virginia. This paper describes retrospective fate and transport modeling of PFOA concentrations in local air, surface water, groundwater, and six municipal water systems based on estimates of historic emission rates from the facility, physicochemical properties of PFOA, and local geologic and meteorological data beginning in 1951. We linked several environmental fate and transport modeling systems to model PFOA air dispersion, transit through the vadose zone, surface water transport, and groundwater flow and transport. These include AERMOD, PRZM-3, BreZo, MODFLOW, and MT3DMS. Several thousand PFOA measurements in municipal well water have been collected in this region since 1998. Our linked modeling system performs better than expected, predicting water concentrations within a factor of 2.1 of the average observed water concentration for each of the six municipal water districts after adjusting the organic carbon partition coefficient to fit the observed data. After model calibration, the Spearman's rank correlation coefficient for predicted versus observed water concentrations is 0.87. These models may be useful for estimating past and future public well water PFOA concentrations in this region.

Background: Perfluorooctanoic acid (PFOA) is a perfluoroalkyl acid found in > 99% of Americans. Its health effects are unknown. Prior estimates of serum half-life range from 2.3 to 3.8 years., Objectives: We assessed the impact of years of residence and years since residing in the study area on serum PFOA concentration in a sample of current and former residents who were exposed to PFOA emissions from an industrial facility in six water districts in West Virginia and Ohio., Methods: Serum samples and questionnaires, including residential history, were collected in 2005-2006. We modeled log serum PFOA (nanograms per milliliter) for current residents as a function of years of residence in a water district, adjusted for a variety of factors. We modeled the half-life in former residents who lived in two water districts with high exposure levels using a two-segment log-linear spline., Results: We modeled serum PFOA concentration in 17,516 current residents as a function of years of residence (R2 = 0.68). Years of residence was significantly associated with PFOA concentration (1% increase in serum PFOA/year of residence), with significant heterogeneity by water district. Half-life was estimated in two water districts comprising a total of 1,573 individuals. For the participants included in our analyses, we found that years since residing in a water district was significantly associated with serum PFOA, which yielded half-lives of 2.9 and 8.5 years for water districts with higher and lower exposure levels, respectively., Conclusion: Years of residence in an exposed water district is positively associated with observed serum PFOA in 2005-2006. Differences in serum clearance rate between low- and high-exposure water districts suggest a possible concentration-dependent or time-dependent clearance process or inadequate adjustment for background exposures.

Background: Drinking water in multiple water districts in the Mid-Ohio Valley has been contaminated with perfluorooctanoic acid (PFOA), which was released by a nearby DuPont chemical plant. Two highly contaminated water districts began granular activated carbon filtration in 2007., Objectives: To determine the rate of decline in serum PFOA, and its corresponding half-life, during the first year after filtration., Methods: Up to six blood samples were collected from each of 200 participants from May 2007 until August 2008. The primary source of drinking water varied over time for some participants; our analyses were grouped according to water source at baseline in May-June 2007., Results: For Lubeck Public Service District customers, the average decrease in serum PFOA concentrations between May-June 2007 and May-August 2008 was 32 ng/mL (26%) for those primarily consuming public water at home (n = 130), and 16 ng/mL (28%) for those primarily consuming bottled water at home (n = 17). For Little Hocking Water Association customers, the average decrease in serum PFOA concentrations between November-December 2007 and May-June 2008 was 39 ng/mL (11%) for consumers of public water (n = 39) and 28 ng/mL (20%) for consumers of bottled water (n = 11). The covariate-adjusted average rate of decrease in serum PFOA concentration after water filtration was 26% per year (95% confidence interval, 2528% per year)., Conclusions: The observed data are consistent with first-order elimination and a median serum PFOA half-life of 2.3 years. Ongoing follow-up will lead to improved half-life estimation.

Objectives: The objective of this study was to determine the incidence of renal disease among workers with silicosis., Methods: A population of 1,328 workers with definite silicosis and adequate work history information, drawn from three states with silicosis surveillance systems, was followed. Renal disease was ascertained via linkage of the cohort with a United States register (which has existed since 1977) of end-stage renal disease., Results: In the first analysis, it was assumed that the risk of end-stage renal disease began upon exposure to silica. In this analysis 12 cases of end-stage renal disease were found versus 15.6 expected, for a rate ratio of 0.77. Four cases of glomerular end-stage renal disease were found (standardized incidence ratio 2.65, 95% confidence interval 0.56-5.25). It is possible that some persons with end-stage renal disease died before being entered into the silicosis registers. In a second analysis, person-time at risk was assumed to begin at the date of entry into the silicosis register. A rate ratio of 1.67 (95% confidence interval 0.76-3.17) was found for end-stage renal disease on the basis of nine observed cases., Conclusions: The results do not clearly show that patients with silicosis have an excess of end-state renal disease, although they do suggest an excess of glomerular end-stage renal disease. Analyses were limited by small numbers and possible selection biases.

The International Agency for Research on Cancer (IARC) has found that the evidence for the carcinogenicity of beryllium is sufficient based on animal data but "limited" based on human data. This analysis reports on a retrospective cohort mortality study among 9,225 male workers employed at seven beryllium processing facilities for at least 2 days between January 1, 1940, and December 31, 1969. Vital status was ascertained through December 31, 1988. The standardized mortality ratio (SMR) for lung cancer in the total cohort was 1.26 (95% confidence interval [CI] = 1.12-1.42); significant SMRs for lung cancer were observed for two of the oldest plants located in Lorain, Ohio (SMR = 1.69; 95% CI = 1.28-2.19) and Reading, Pennsylvania (SMR = 1.24; 95% CI = 1.03-1.48). For the overall cohort, significantly elevated SMRs were found for "all deaths" (SMR = 1.05; 95% CI = 1.01-1.08), "ischemic heart disease" (SMR = 1.08; 95% CI = 1.01-1.14), "pneumoconiosis and other respiratory diseases" (SMR = 1.48; 95% CI = 1.21-1.80), and "chronic and unspecified nephritis, renal failure, and other renal sclerosis" (SMR = 1.49; 95% CI = 1.00-2.12). Lung cancer SMRs did not increase with longer duration of employment, but did increase with longer latency (time since first exposure). Lung cancer was particularly elevated (SMR = 3.33; 95% CI = 1.66-5.95) among workers at the Lorain plant with a history of (primarily) acute beryllium disease, which is associated with very high beryllium exposure. The lung cancer excess was not restricted to plants operating in the 1940s, when beryllium exposures were known to be extraordinarily high. Elevated lung cancer SMRs were also observed for four of the five plants operating in the 1950s for workers hired during that decade. Neither smoking nor geographic location fully explains the increased lung cancer risk. Occupational exposure to beryllium compounds is the most plausible explanation for the increased risk of lung cancer observed in this study. Continued mortality follow-up of this cohort will provide a more definitive assessment of lung cancer risk at the newer plants and among cohort members hired in the 1950s or later at the older plants. Further clarification of the potential for specific beryllium compounds to induce lung cancer in humans, and the possible contribution of other exposures in specific processes at these plants, would require a nested case-control study. We are currently assessing whether available industrial hygiene data would support such an analysis.

Commercial city directories, currently produced in 1,250 United States cities, potentially provide yearly information on occupation and employer for all city residents over age 18 years. To investigate the usefulness of these occupational data, the authors have conducted a case-control study of male bladder cancer mortality in Hamilton County, Ohio (which includes Cincinnati). A total of 731 bladder cancer cases who died during 1960-1982 were matched on age, sex, race, date-of-death, and residence at death to two controls per case. Risks of bladder cancer death were calculated by occupation, industry, and specific employer, using both city directories (multiple statements) and death certificates (single statement). Four companies showed a significant excess bladder cancer risk when using city directories. Only one would have been identified using death certificates, which ask for usual lifetime type of industry rather than a specific company name. Using city directories, significant positive associations were found between bladder cancer and occupation as an engineer, tailor, carpenter, furnace operator, blending machine operator, chemist, pressing machine operator, house cleaner, or salesman. For industry, the authors found significant positive associations for the textile, chemical, grain mill, foundry, petroleum, building service, entertainment, and advertising industries. A significant increase in risk for those with 20 or more years of employment was seen for those employed as truck drivers and furnace operators, or those employed in the railroad industry. A check of the validity of city directory data indicated that 77 per cent of the listings agreed with Social Security earnings reports for employer in any given year. One limitation of Hamilton County city directory data was the fairly large number of yearly listings without any occupational data (15 per cent for occupation, 36 per cent for employer). While city directory data do provide work history over time, unlike death certificates, such data are available only for years of residence in the city in question.