Serum Perfluorooctanoic Acid Concentrations Research Articles

PFAS (per- and polyfluoroalkyl substances) and asthma in young children: NHANES 2013–2014

Per- and polyfluoroalkyl substances (PFAS) are a class of persistent chemicals used as industrial surfactants, fire-fighting foams, and textile treatments. Early childhood exposure to perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS) may affect the immune system to increase the risk of allergic and respiratory diseases. However, there are substantial gaps in our knowledge about the relationship between PFAS and immune-mediated outcomes such as asthma in children. Thus, we examined the cross-sectional associations of serum PFOA, PFOS, PFNA, and PFHxS concentrations with childhood asthma. We used data from children aged 3-11 years who participated in the National Health and Nutrition Examination Survey (2013-2014). Serum PFAS concentrations were measured in serum using analytical chemistry methods. Asthma was assessed by parent-reported, doctor-diagnosed, asthma using a standardized questionnaire. Controlling for covariates, we estimated odds ratios for asthma per standard deviation increase in ln-transformed serum PFAS concentrations (n=607). We also examined effect measure modification by child age, sex, and race/ethnicity. PFOA (1.1; 95% CI: 0.8, 1.4), PFOS (1.2; 95% CI: 0.8, 1.7), PFNA (1.1; 95% CI: 0.8, 1.6), and PFHxS (1.1; 95% CI: 0.9, 1.6) were weakly associated with an increased odds of asthma. Age modified associations between serum PFOS, but not other serum PFAS concentrations, and odds of asthma (age x PFOS interaction term p-value=0.03). Sex and race/ethnicity did not modify these associations. We observed some evidence that serum PFAS concentrations are weakly associated with increased asthma prevalence in US children.

Serum concentrations of perfluoroalkyl substances and their association with osteoporosis in a population in Jeddah, Saudi Arabia

Human exposure to poly- and perfluoroalkyl substances (PFASs) is widespread and has received considerable attention in recent years due to their link with adverse health outcomes, including bone health. Nevertheless, no earlier studies have reported serum PFAS concentrations, and their association with incident osteoporosis in populations in Saudi Arabia. In this clinical case-control study, serum samples collected from 208 individuals (n = 100 cases and n = 108 controls) aged 40–89 years from Jeddah, Saudi Arabia, were analyzed for 17 PFASs. Unconditional logistic regression was used to calculate odds ratios (ORs) for association between serum PFAS concentrations and osteoporosis, stratified by gender, age, serum calcium and vitamin D, previous history of fractures and thyroid disorders. Perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorobutanoic acid (PFBA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), perfluoro-n-pentanoic acid (PFPeA) and perfluoroundecanoic acid (PFUnDA) were detected in >80% of serum samples analyzed. PFOS (overall median concentration: 5.08 ng/mL), PFHxS (1.49 ng/mL), PFOA (1.33 ng/mL) and PFNA (0.55 ng/mL) accounted for 94% and 80% of the total serum PFASs concentrations in cases and controls, respectively. Serum PFOA, PFNA and PFUnDA concentrations increased with age in Saudi women. Results from the crude models showed that individuals in the 2nd, 3rd and 4th quartiles of serum PFAS concentrations had 2.3–96-fold increase in odds of diagnosis for osteoporosis compared with those in the 1st quartile (rank order: PFUnDA > PFOA > PFNA > PFOS > PFHxS). Our results suggest that exposure to PFOA, PFOS, PFNA, PFHxS and PFUnDA was associated with osteoporosis in this sample of adult Saudi population.

Pharmacokinetic bias analysis of an association between clinical thyroid disease and two perfluoroalkyl substances

Exposure to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) has been associated with the occurrence of thyroid disease in some epidemiologic studies. We hypothesized that in a specific epidemiologic study based on the National Health and Nutrition Examination Survey, the association of clinical thyroid disease with serum concentration of PFOA and PFOS was due to reverse causality. Thyroid hormone affects glomerular filtration, which in turn affects excretion of PFOA and PFOS. We evaluated this by linking a model of thyroid disease status over the lifetime to a physiologically based pharmacokinetic model of PFOA and PFOS. Using Monte Carlo methods, we simulated the target study population and analyzed the data using multivariable logistic regression. The target and simulated populations were similar with respect to age, estimated glomerular filtration rate, serum concentrations of PFOA and PFOS, and prevalence of clinical thyroid disease. The analysis showed little or no evidence of bias from the hypothesized mechanism. The largest bias was for the fourth quartile of PFOA in females, with an odds ratio of 0.93 (95% CI, 0.90, 0.97). The reported odds ratio of clinical thyroid disease for this group was 1.63 (1.07, 2.47), and if it were corrected for the bias would have been 1.74 (1.14, 2.65). Our results suggest that little of the reported association in the target study was due to reverse causality.

Quantitative bias analysis of the association between subclinical thyroid disease and two perfluoroalkyl substances in a single study

Exposure to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) has been associated with the occurrence of thyroid disease in some epidemiologic studies. We hypothesized that in a specific epidemiologic study based on the National Health and Nutrition Examination Survey, the association of subclinical thyroid disease with serum concentration of PFOA and PFOS was due to reverse causality. Thyroid hormone affects glomerular filtration, which in turn affects excretion of PFOA and PFOS. We evaluated this by linking a model of thyroid disease status over the lifetime to physiologically based pharmacokinetic models of PFOA and PFOS. Using Monte Carlo methods, we simulated the target study population and analyzed the data using multivariable logistic regression. The target and simulated populations were similar with respect to age, estimated glomerular filtration rate, serum concentrations of PFOA and PFOS, and prevalence of subclinical thyroid disease. Our findings suggest that in the target study the associations with subclinical hypothyroidism were overstated and the results for subclinical hyperthyroidism were, in general, understated. For example, for subclinical hypothyroidism in men, the reported odds ratio per ln(PFOS) increase was 1.98 (95% CI 1.19–3.28), whereas in the simulated data the bias due to reverse causality gave an odds ratio of 1.19 (1.16–1.23). Our results provide evidence of bias due to reverse causality in a specific cross-sectional study of subclinical thyroid disease with exposure to PFOA and PFOS among adults.

Metabolomics of childhood exposure to perfluoroalkyl substances: a cross-sectional study.

Exposure to perfluoroalkyl substances (PFAS), synthetic and persistent chemicals used in commercial and industrial processes, are associated with cardiometabolic dysfunction and related risk factors including reduced birth weight, excess adiposity, and dyslipidemia. Identifying the metabolic changes induced by PFAS exposure could enhance our understanding of biological pathways underlying PFAS toxicity. To identify metabolic alterations associated with serum concentrations of four PFAS in children using a metabolome-wide association study. We performed untargeted metabolomic profiling by liquid chromatography with ultra-high-resolution mass spectrometry, and separately quantified serum concentrations of perfluorooctanoic acid, perfluorooctanesulfonic acid, perfluorononanoic acid, and perfluorohexanesulfonic acid (PFHxS) for 114 8-year old children from Cincinnati, OH. We evaluated associations between each serum PFAS concentration and 16,097 metabolic features using linear regression adjusted for child age, sex, and race with a false discovery rate < 20%. We annotated PFAS-associated metabolites and conducted pathway enrichment analyses. Serum PFAS concentrations were associated with metabolic features annotated primarily as lipids and dietary factors. Biological pathways associated with all four PFAS included arginine, proline, aspartate, asparagine, and butanoate metabolism. In this cross-sectional study, childhood serum PFAS concentrations were correlated with metabolic pathways related to energy production and catabolism. Future studies should determine whether these pathways mediate associations between PFAS exposure and childhood cardiometabolic health.

Cross-sectional study of the association between serum perfluorinated alkyl acid concentrations and dental caries among US adolescents (NHANES 1999–2012)

Study objectivesPerfluoroalkyl acids (PFAAs) are a class of anthropogenic and persistent compounds that may impact some biological pathways related to oral health. The objective of our study was to estimate...

Perfluorooctanoic Acid (PFOA): Environmental Sources, Chemistry, Toxicology, and Potential Risks

ABSTRACT Attention regarding perfluoroalkyl and polyfluoroalkyl substances (PFAS) has increased in recent years, due to recognition of widespread environmental presence, recognition of a chemical structure that confers resistance to degradation, and reported health concerns. Historical common exposure sources include food, drinking water, occupational circumstances, and products in commerce (e.g., carpeting, clothing, paper products). Early-2000’s data showed perfluorooctanoic acid (PFOA) was present in blood samples from nearly all the U.S. general population (>99%). Alterations in industrial manufacturing processes, increased regulatory scrutiny, and advanced water treatment options have reduced the reported human body burden of PFAS in the U.S., including for PFOA. Human serum concentrations of PFOA, which do not identify the source(s) of exposure, have exhibited a substantial decrease (~63%) between the 1999–2000 and the 2013–2014 NHANES monitoring by the Centers for Disease Control and Prevention (CDC). With respect to both noncancer and potential cancer effects that may be associated with reported serum levels of PFOA, conclusions regarding an absence of effects, or insufficient information to suggest adverse effects, prevent a consistent conclusion about the occurrence and magnitude of human health effects. In the last several years, a number of state and federal agencies have developed health advisories or guideline values for drinking water exposure that are in the sub-ppb range. In 2016, a USEPA Health Advisory of 0.07 ppb was released, which stands in contrast to 2016 Health-based Values from Health Canada ranging from 0.2 ppb (PFOA) to 30 ppb, and a few other U.S. states with values even less than that of USEPA (e.g., MN, NJ, VT). Further work is necessary to distinguish in transparent fashion between drinking water levels that intentionally are set on a conservative basis to protect human health vs exposure levels that may be associated with tangible adverse effects.

Longitudinal trends of per- and polyfluoroalkyl substances in children's serum

Studies suggest negative health impacts from early life exposure to per- and polyfluoroalkyl substances (PFASs). However, information on longitudinal exposure to PFASs during childhood is scarce for background-exposed individuals. This study sought to fill this gap by investigating children's longitudinal exposure trends through measurement of PFAS serum concentrations and calculation of body burdens (μg, total in body). Blood of 54 Finnish children was sampled 2005–2015 and analyzed for 20 PFASs at 1, 6 and 10.5 years of age. The body burden was calculated by multiplying the serum concentration by the volume of distribution and the bodyweight for each individual. Associations between serum concentrations or body burdens and parameters, such as sex, breastfeeding duration, body mass index as well as indoor dust and air PFAS concentrations, were evaluated. Serum concentrations of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorohexane sulfonic acid (PFHxS) decreased significantly (p < 0.001) with age. In contrast to serum concentrations, body burdens stayed unchanged or even increased significantly (p < 0.05), except for PFOA in female children. Breastfeeding duration was positively correlated (p < 0.001) with serum concentrations of PFHxS, PFOS, PFOA and PFNA at 1 year of age. Some associations were found at 10.5 years with sex and indoor PFAS concentrations. Observations of longitudinal decreasing trends of serum concentrations can be misleading for understanding exposure levels from external media during childhood, as the serum concentration is influenced by parallel temporal changes and growth dilution. Body burdens account for growth dilution and thus better reflect differences in early-life to adolescence exposure than serum concentrations.

Metabolomics of Childhood Exposure to Perfluorooctanoic Acid: A Cross-Sectional Study

Background: Exposure to perfluorooctanoic acid (PFOA), a synthetic and persistent chemical used in commercial and industrial processes, is associated with reduced birth weight, increased adiposity, dyslipidemia, and liver injury. These diverse toxic effects suggest that PFOA elicits multiple biological responses. Identifying the metabolic changes induced by PFOA exposure could enhance our understanding of potential biological mechanisms.Study Objective: To identify metabolic changes associated with serum PFOA concentrations in 8-year old children using a metabolome-wide association study (MWAS).Methods: Using venous blood samples collected from 120 8-year old children in Cincinnati, OH, we quantified serum PFOA concentrations and performed untargeted metabolomic profiling by liquid chromatography-high-resolution mass spectrometry. We evaluated metabolic variations associated with PFOA concentrations using linear regression and false discovery rate (FDR) &amp;lt;20%. We identified associated metabolites with the METLIN mass spectral database and metabolic pathway enrichment analysis.Results: At FDR&amp;lt;20%, higher serum PFOA concentrations were associated with 239 detected chemical signals; 130 were positive associations. Initial annotation of the mass spectral data showed that both endogenous metabolites and perfluoroalkyl chemicals were associated with PFOA exposure. Using untargeted metabolomics, we detected PFOA, perfluorooctanesulfonic acid, and additional signals consistent with fluorinated chemicals. Biological alterations associated with PFOA concentrations included keratin sulfate degradation and metabolism of purine, caffeine, Vitamin E, linoleate, urea cycle/amino groups, glyoxylate, dicarboxylate, and galactose, consistent with changes to immunological, oxidative stress and catabolism pathways.Conclusions: This is the first study to perform a MWAS with PFOA exposure in children and provides new insights into the biological responses associated with PFOA exposure.

Prenatal exposure to perfluoroalkyl substances and adipocytokines: the HOME Study.

Gestational perfluoroalkyl substances exposure has been associated with decreased birthweight. We determined if gestational perfluoroalkyl substances exposure was associated with fetal metabolic markers using data from the HOME Study, a prospective birth cohort of pregnant women and their children in Cincinnati, Ohio. Maternal serum concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid, and perfluorohexane sulfonic acid were quantified. We measured neonatal adipocytokine (leptin and adiponectin) concentrations in umbilical cord serum, and estimated percent differences with a 2-fold increase in maternal perfluoroalkyl substances concentrations among 230 mother-infant pairs. Median maternal serum PFOA and PFOS concentrations were 5.6 ng/mL and 14 ng/mL, respectively. Leptin was positively correlated with infant birthweight (p < 0.001). There were no statistically significant associations between maternal perfluoroalkyl substances and neonatal adipocytokine concentrations; each 2-fold increase in PFOA was associated with a non-significant increase in leptin (5%; 95% CI: -10, 22) and adiponectin (7%; 95% CI: -4, 19). Despite known associations with reduced birthweight, gestational serum perfluoroalkyl substances concentrations were not associated with neonatal adipocytokine concentrations. Further exploration of pathways of perfluoroalkyl substances associated changes in birthweight may help identify biomarkers that could be used to identify at-risk populations and develop interventions.

Per- and polyfluoroalkyl substance (PFAS) exposure assessment in a community exposed to contaminated drinking water, New Hampshire, 2015

Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals used in manufacturing that resist environmental degradation, can leach into drinking water, and bioaccumulate in tissues. Some studies have shown associations with negative health outcomes. In May 2014, a New Hampshire public drinking water supply was found to be contaminated with PFAS from a former U.S. Air Force base. We established a serum testing program to assess PFAS exposure in the affected community. Serum samples and demographic and exposure information were collected from consenting eligible participants. Samples were tested for PFAS at three analytical laboratories. Geometric means and 95% confidence intervals were calculated and analyzed by age and exposure variables. A total of 1578 individuals provided samples for PFAS testing; >94% were found to have perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorohexane sulfonic acid (PFHxS) detectable in serum. Geometric mean serum concentrations of PFOS, PFOA, and PFHxS were 8.6 μg/L (95% CI:8.3-8.9), 3.1 μg/L (95% CI: 3.0-3.2), and 4.1 μg/L (95% CI: 3.9-4.3), respectively, which were statistically higher than the general U.S. Significant associations were observed between PFAS serum concentrations and age, time spent in the affected community, childcare attendance, and water consumption. PFOS, PFOA, and PFHxS were found in significantly higher levels in the affected population, consistent with PFAS drinking water contamination. Given increased recognition of PFAS contamination in the U.S, a coordinated national response is needed to improve access to biomonitoring and understand health impacts.

Online Serum PFOA Calculator for Adults.

Summary:Perfluorooctanoic acid (PFOA) is a persistent environmental contaminant that has been detected in public water systems in the United States alone. A variety of epidemiological investigations of PFOA have been published, mostly using measured or modeled serum PFOA concentrations as the exposure metric. Comparison of drinking water PFOA concentrations to those study findings or to typical serum concentrations requires pharmacokinetic modeling. This brief communication describes an online Javascript calculator that easily plots the expected serum PFOA concentration over time and at steady state for adults after starting or stopping consumption of PFOA-contaminated water. Two examples of usage are provided, including increasing serum PFOA after ongoing consumption of contaminated water at the federal limit, and decreasing serum PFOA after carbon filtration began in a contaminated water system. https://doi.org/10.1289/EHP2820

Physiologically based pharmacokinetic modeling of human exposure to perfluorooctanoic acid suggests historical non drinking-water exposures are important for predicting current serum concentrations

Manufacturing of perfluorooctanoic acid (PFOA), a synthetic chemical with a long half-life in humans, peaked between 1970 and 2002, and has since diminished. In the United States, PFOA is detected in the blood of >99% of people tested, but serum concentrations have decreased since 1999. Much is known about exposure to PFOA in drinking water; however, the impact of non-drinking water PFOA exposure on serum PFOA concentrations is not well characterized.The objective of this research is to apply physiologically based pharmacokinetic (PBPK) modeling and Monte Carlo analysis to evaluate the impact of historic non-drinking water PFOA exposure on serum PFOA concentrations.In vitro to in vivo extrapolation was utilized to inform descriptions of PFOA transport in the kidney. Monte Carlo simulations were incorporated to evaluate factors that account for the large inter-individual variability of serum PFOA concentrations measured in individuals from North Alabama in 2010 and 2016, and the Mid-Ohio River Valley between 2005 and 2008.Predicted serum PFOA concentrations were within two-fold of experimental data. With incorporation of Monte Carlo simulations, the model successfully tracked the large variability of serum PFOA concentrations measured in populations from the Mid-Ohio River Valley. Simulation of exposure in a population of 45 adults from North Alabama successfully predicted 98% of individual serum PFOA concentrations measured in 2010 and 2016, respectively, when non-drinking water ingestion of PFOA exposure was included.Variation in serum PFOA concentrations may be due to inter-individual variability in the disposition of PFOA and potentially elevated historical non-drinking water exposures.

Maternal serum PFOA concentration and DNA methylation in cord blood: A pilot study

Perfluorooctanoic acid (PFOA), a perfluoroalkyl substance, is commonly detected in the serum of pregnant women and may impact fetal development via epigenetic re-programming. In a pilot study, we explored associations between serum PFOA concentrations during pregnancy and offspring peripheral leukocyte DNA methylation at delivery in women with high (n = 22, range: 12–26 ng/mL) and low (n = 22, range: 1.1–3.1 ng/mL) PFOA concentrations. After adjusting for cell type, child sex, and income, we did not find differences in CpG methylation in the two exposure groups that reached epigenome-wide significance. Among the 20 CpGs with the lowest p-values we found that seven CpG sites in three genes differed by exposure status. In a confirmatory cluster analysis, these 20 CpGs clustered into two groups that perfectly identified exposure status. Future studies with larger sample sizes should confirm these findings and determine if PFOA-associated changes in DNA methylation underlie potential health effects of PFOA.

Per- and polyfluoroalkyl substances in human serum and urine samples from a residentially exposed community

BackgroundPer- and polyfluoroalkyl substances (PFAS) are considered chemicals of emerging concern, in part due to their environmental and biological persistence and the potential for widespread human exposure. In 2007, a PFAS manufacturer near Decatur, Alabama notified the United States Environmental Protection Agency (EPA) it had discharged PFAS into a wastewater treatment plant, resulting in environmental contamination and potential exposures to the local community. ObjectivesTo characterize PFAS exposure over time, the Agency for Toxic Substances and Disease Registry (ATSDR) collected blood and urine samples from local residents. MethodsEight PFAS were measured in serum in 2010 (n=153). Eleven PFAS were measured in serum, and five PFAS were measured in urine (n=45) from some of the same residents in 2016. Serum concentrations were compared to nationally representative data and change in serum concentration over time was evaluated. Biological half-lives were estimated for perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorohexane sulfonic acid (PFHxS) using a one-compartment pharmacokinetic model. ResultsIn 2010 and 2016, geometric mean PFOA and PFOS serum concentrations were elevated in participants compared to the general U.S. population. In 2016, the geometric mean PFHxS serum concentration was elevated compared to the general U.S. population. Geometric mean serum concentrations of PFOA, PFOS, and perfluorononanoic acid (PFNA) were significantly (p≤0.0001) lower (49%, 53%, and 58%, respectively) in 2016 compared to 2010. Half-lives for PFOA, PFOS, and PFHxS were estimated to be 3.9, 3.3, and 15.5years, respectively. Concentrations of PFOA in serum and urine were highly correlated (r=0.75) in males. ConclusionsSerum concentrations of some PFAS are decreasing in this residentially exposed community, but remain elevated compared to the U.S. general population.

Polyfluoroalkyl substance exposure in the Mid-Ohio River Valley, 1991–2012

BackgroundIndustrial discharges of perfluorooctanoic acid (PFOA) to the Ohio River, contaminating water systems near Parkersburg, WV, were previously associated with nearby residents' serum PFOA concentrations above US general population medians. Ohio River PFOA concentrations downstream are elevated, suggesting Mid-Ohio River Valley residents are exposed through drinking water. ObjectivesQuantify PFOA and 10 other per- and polyfluoroalkyl substances (PFAS) in Mid-Ohio River Valley resident sera collected between 1991 and 2013 and determine whether the Ohio River and Ohio River Aquifer are exposure sources. MethodsWe measured eleven PFAS in 1608 sera from 931 participants. Serum PFOA concentration and water source associations were assessed using linear mixed-effects models. We estimated between-sample serum PFOA using one-compartment pharmacokinetics for participants with multiple samples. ResultsIn serum samples collected as early as 1991, PFOA (median = 7.6 ng/mL) was detected in 99.9% of sera; 47% had concentrations greater than US population 95th percentiles. Five other PFAS were detected in greater than 82% of samples; median other PFAS concentrations were similar to the US general population. Serum PFOA was significantly associated with water source, sampling year, age at sampling, tap water consumption, pregnancy, gravidity and breastfeeding. Serum PFOA was 40–60% lower with granular activated carbon (GAC) use. Repeated measurements and pharmacokinetics suggest serum PFOA peaked 2000–2006 for participants using water without GAC treatment; where GAC was used, serum PFOA concentrations decreased from 1991 to 2012. ConclusionsMid-Ohio River Valley residents appear to have PFOA, but not other PFAS, serum concentrations above US population levels. Drinking water from the Ohio River and Ohio River Aquifer, primarily contaminated by industrial discharges 209–666 km upstream, is likely the primary exposure source. GAC treatment of drinking water mitigates, but does not eliminate, PFOA exposure.

Human exposure to perfluoroalkyl substances near a fluorochemical industrial park in China.

Severe perfluoroalkyl substance (PFAS) contaminations have been observed in both surface water and groundwater in the vicinity of Fuxin, China, over the past years, attributing to the fast-growing fluorochemical industries locally. However, little is known about the overall daily intake of PFAS contaminations by Fuxin residents recently. In the present study, ten target PFAS analytes in the blood serum samples collected from 100 non-occupationally exposed healthy residents in Fuxin, with an average age of 47.6years, together with 14 drinking water samples obtained from the public water system (PWS) of Fuxin were analyzed via high-performance liquid chromotography-tandem mass spectrometry (HPLC-MS/MS). As the dominant PFAS contaminant, the serum concentrations of perfluorooctanoic acid (PFOA) in Fuxin residents ranged between <0.05 and 160ng/mL, with a median concentration of 9.4ng/mL, which was higher than those reported previously for Fuxin and other areas worldwide. In drinking water samples, PFOA had a median value of 8.5ng/L, ranging from 7.7 to 8.8ng/L. Based upon the simplified one-compartment pharmacokinetic model, the total daily intake of PFOA for individuals residing in Fuxin ranged from 0.30 to 1.76ng/kg bw/day, with a median of 0.79ng/kg bw/day; furthermore, daily consumption of drinking water from the PWS in Fuxin appeared to contribute 35% of overall PFOA burden in local residents, which was approximately 3-fold higher compared to that estimated for Fuxin residents in 2009.

A Study of Reverse Causation: Examining the Associations of Perfluorooctanoic Acid Serum Levels with Two Outcomes.

Background:Impaired kidney function and earlier menopause were associated with perfluorooctanoic acid (PFOA) serum levels in previous cross-sectional studies. Reverse causation, whereby health outcomes increase serum PFOA, may underlie these associations.Objective:We compared measured (subject to reverse causation) versus modeled (unaffected by reverse causation) serum PFOA in association with these outcomes to examine the possible role of reverse causation in these associations.Methods:In cross-sectional analyses, we analyzed PFOA in relation to self-reported menopause among women (n = 9,192) 30–65 years old and in relation to kidney function among adults > 20 years old (n = 29,499) in a highly exposed Mid-Ohio Valley cohort. Estimated glomerular filtration rate (eGFR, a marker of kidney function) and serum PFOA concentration were measured in blood samples collected during 2005–2006. Retrospective year-specific serum PFOA estimates were modeled independently of measured PFOA based on residential history and plant emissions. Using measured and modeled PFOA in 2005 or 2006 (predictor variables), cross-sectional associations were assessed for eGFR and menopause (yes/no). We also analyzed measured PFOA (dependent variable) in relation to the number of years since menopause.Results:Menopause and eGFR were significantly associated with measured (trend tests: p = 0.013, p = 0.0005, respectively) but not with modeled serum PFOA (p = 0.50, p = 0.76, respectively). Measured PFOA levels increased for the first 7 years after menopause (trend test, p < 0.0001), providing further evidence that the observed association between measured PFOA and menopause is subject to reverse causation for this outcome.Conclusion:Our results support the conjecture that in previous studies, earlier menopause and reduced kidney function are the causes rather than the results of increased measured serum PFOA. These results suggest caution in using biomarkers in cross-sectional studies.Citation:Dhingra R, Winquist A, Darrow LA, Klein M, Steenland K. 2017. A study of reverse causation: examining the associations of perfluorooctanoic acid serum levels with two outcomes. Environ Health Perspect 125:416–421; http://dx.doi.org/10.1289/EHP273

Contribution of Direct and Indirect Exposure to Human Serum Concentrations of Perfluorooctanoic Acid in an Occupationally Exposed Group of Ski Waxers.

The contribution of direct (i.e., uptake of perfluorooctanoic acid (PFOA) itself) and indirect (i.e., uptake of 8:2 fluorotelomer alcohol (FTOH) and metabolism to PFOA) exposure to PFOA serum concentrations was investigated using a dynamic one-compartment pharmacokinetic (PK) model. The PK model was applied to six occupationally exposed ski waxers for whom direct and indirect exposures via inhalation were characterized using multiple measurements with personal air sampling devices. The model was able to predict the diverging individual temporal trends of PFOA in serum with correlation coefficients of 0.82-0.94. For the four technicians with high initial concentrations of PFOA in serum (250-1050 ng/mL), the ongoing occupational exposure (both direct and indirect) was of minor importance and net depuration of PFOA was observed throughout the ski season. An estimated average intrinsic elimination half-life of 2.4 years (1.8-3.1 years accounting for variation between technicians and model uncertainty) was derived for these technicians. The remaining two technicians, who had much lower initial serum concentrations (10-17 ng/mL), were strongly influenced by exposure during the ski season with indirect exposure contributing to 45% of PFOA serum concentrations. On the basis of these model simulations, an average metabolism yield of 0.003 (molar concentration basis; uncertainty range of 0.0006-0.01) was derived for transformation of 8:2 FTOH to PFOA. An uncertainty analysis was performed, and it was determined that the input parameters quantifying the intake of PFOA were mainly responsible for the uncertainty of the metabolism yield and the initial concentration of PFOA in serum was mainly contributing to the uncertainty of estimated serum half-lives.

Preliminary Associations between the Detection of Perfluoroalkyl Acids (PFAAs) in Drinking Water and Serum Concentrations in a Sample of California Women

This study compared detection of perfluoroalkyl acids (PFAAs) in public drinking water with PFAA serum concentrations for 1566 California women. PFAA occurrence in drinking water from U.S. EPA’s third Unregulated Contaminant Monitoring Rule (UCMR3) database was linked by residential zip code to study participants. Detectable water concentrations of perfluorooctanoic acid (PFOA) ranged from 0.020 to 0.053 μg/L and of perfluorooctanesulfonic acid (PFOS) from 0.041 to 0.156 μg/L. Forty percent of detectable concentrations exceeded the 2016 Health Advisory Level of 0.07 μg/L for combined PFOA and PFOS concentrations. Serum concentrations of PFOS and PFOA significantly differed between participants with and without detectable measures of these compounds in water (Wilcoxon P ≤ 0.0007). Median serum concentrations of PFOS and PFOA were 29% and 38% higher, respectively, among those with detectable levels in water compared to those without detectable levels. Validation of this approach and replication of these res...