Serum Perfluorooctanoic Acid Concentrations Research Articles

Temporal Trend of Serum Perfluorooctanoic Acid and Perfluorooctane Sulfonic Acid among U.S. Adults with or without Comorbidities in NHANES 1999-2018.

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are associated with adverse health effects. This study examined the trend of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) levels in individuals with and without pre-existing comorbidities. We analyzed the characteristics of 13,887 participants across nine U.S. NHANES cycles (1999-2000 to 2017-2018) and calculated the geometric mean (GM) of PFOA and PFOS levels, standardized by sex and age. A joinpoint regression model was used to analyze the temporal trends of serum PFOA and PFOS levels. We observed declining PFOA and PFOS serum levels among adults in NHANES from 1999-2000 to 2017-2018. Serum PFOA and PFOS concentrations were higher in men, smokers, and individuals with pre-existing CKD, hyperlipidemia, CVD, and cancer. We observed faster decline rates in PFOA levels among individuals with diabetes and CKD and faster decline rates in PFOS levels among individuals with diabetes and those without CKD. This study provided evidence of varying levels and changing trends of PFOA and PFOS between groups with and without established chronic disease, highlighting the role of environmental chemicals in the onset and development of chronic diseases.

Determinants of PFOA Serum Half-Life after End of Exposure: A Longitudinal Study on Highly Exposed Subjects in the Veneto Region.

Perfluoroalkyl substances (PFAS) are widely used, ubiquitous, and highly persistent man-made chemicals. Groundwater of a vast area of the Veneto Region (northeastern Italy) was found to be contaminated by PFAS from a manufacturing plant active since the late 1960s. As a result, residents were overexposed to PFAS through drinking water until 2013, mainly to perfluorooctanoic acid (PFOA). The aim of the present study was to estimate the rates of decline in serum PFOA and their corresponding serum half-lives, while characterizing their determinants. We investigated 5,860 subjects more than 14 years of age who enrolled in the second surveillance round of the regional health surveillance program. Two blood samples were collected between 2017 and 2022 (average time between measurements: 4 years). Serum PFOA excretion rates and half-lives were estimated based on linear mixed effect models, modeling subject-specific serum PFOA concentrations over time and correcting for background concentrations. For modeling determinants of half-life [age, sex, body mass index (BMI), smoking-habit, alcohol consumption, and estimated glomerular filtration rate (eGFR)], we added interaction terms between each covariate and the elapsed time between measurements. Perfluorooctanesulfonate (PFOS) and perfluorohexanesulfonic acid (PFHxS) apparent half-lives were also estimated. A separate analysis was conducted in children (). All analyses were stratified by sex. Median initial serum concentrations of PFOA was (range: 0.5-1,090), with a median reduction of 62.45%. The mean estimated PFOA half-life was 2.36 years [95% confidence interval (CI): 2.33, 2.40], shorter in women (2.04; 95% CI: 2.00, 2.08) compared to men (2.83; 95% CI: 2.78, 2.89). Half-lives varied when stratified by some contributing factors, with faster excretion rates in nonsmokers and nonalcohol drinkers (especially in males). This study, to our knowledge the largest on PFOA half-life, provides precise estimates in young adults whose exposure via drinking water has largely ceased. For other PFAS, longer half-lives than reported in other studies can be explained by some ongoing exposure to PFAS via other routes. https://doi.org/10.1289/EHP13152.

Elevated levels of serum per- and poly-fluoroalkyl substances (PFAS) in contact lens users of U.S. young adults

Despite evidence indicating the presence of per- and poly-fluoroalkyl substances (PFAS) in contact lenses (CL), it remains unclear whether CL use increases PFAS exposure in the general population. We aimed to determine whether CL users have higher serum concentrations of PFAS than non-users, using data of 1660 adults aged 20–39 years participating in the National Health and Nutrition Examination Survey 1999–2000 and 2003–2008. We classified the individuals into CL users and non-users using the record of vision correction types during a vision test. Serum concentrations of six individual PFAS were measured, and the overall PFAS burden was calculated by item response theory scoring. Survey-weighted linear models were used to compare serum PFAS levels between CL users and non-users after adjusting for covariates. Distributions of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) concentrations were compared with reference values (e.g., human biomonitoring [HBM]-II values) indicating potential for adverse health effects. Survey-weighted linear models revealed that covariate-adjusted serum PFOA concentration was higher in CL users (geometric mean [GM]: 3.68 ng/mL; 95% CI: 3.00, 4.50) than in non-users (GM: 3.27 ng/mL; 95% CI: 2.81, 3.80; p = 0.02). Similarly, CL users had a significantly higher serum PFHxS concentration (GM: 1.58 ng/mL; 95% CI: 1.13, 2.20) than non-users (GM: 1.30 ng/mL; 95% CI: 1.10, 1.66; p = 0.03). CL users also had a significantly higher overall burden of PFAS than non-users. The differences in PFAS concentrations between CL users and non-users were more pronounced in females than in males. Moreover, a larger proportion of lens users (4.5%), compared to non-users (3.9%), had PFOA concentrations above the HBM-II, where adverse health effects are expected from PFOA exposure. This study suggests that CL use in general U.S. young adults may contribute significantly to PFAS body burden, which can potentially lead to public health problem.

Association between probiotic consumption and serum perfluoroalkyl and polyfluoroalkyl substances (PFAS): results from NHANES, 2003–2018

BackgroundPerfluoroalkyl and polyfluoroalkyl substances (PFAS) represent a category of pervasive and enduring environmental pollutants that present a risk to human health. Although growing evidence suggests that probiotics can potentially alleviate the adverse effects of PFAS, large cross-sectional studies on the relationship between probiotic consumption and PFAS remain lacking.ObjectiveThe objective of this study is to assess the association between the exposure of probiotics and serum levels of PFAS.MethodsThis analysis included individuals aged 20 and above who took part in the National Health and Nutrition Examination Survey (NHANES) between 2003 and 2018. Probiotic consumption was considered when a participant reported consuming yogurt during the two 24-h dietary recall or using a probiotic supplement in dietary supplement questionnaires over the past 30 days.ResultsThis study involved 9469 adults, out of which 1333 had been exposed to probiotics. We found negative associations between probiotic consumption and serum concentrations of perfluorooctanoic acid (PFOA) (β: − 0.19, 95% CI − 0.35 to − 0.02; P = 0.027), and perfluorooctane sulfonic acid (PFOS) (β: − 0.1.27, 95% CI − 2.23 to − 0.32; P = 0.010). The consumption of probiotic supplements alone was associated with reduced perfluorononanoic acid (PFNA) (β: − 0.19, 95% CI − 0.28 to − 0.10; P < 0.001). No statistically significant association was identified between probiotic consumption and perfluorohexane sulphonic acid (PFHxS).ConclusionIn this cross-sectional, nationally representative study, probiotic ingestion was negatively associated with several serum PFAS compounds. These findings carry substantial implications for designing interventions that target the reduction of accumulated PFAS levels in the body and mitigating the resulting adverse health effects.

Serum per- and polyfluoroalkyl substance concentrations and longitudinal change in post-infection and post-vaccination SARS-CoV-2 antibodies

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous throughout the United States. Previous studies have shown PFAS exposure to be associated with a reduced immune response. However, the relationship between serum PFAS and antibody levels following SARS-CoV-2 infection or COVID-19 vaccination has not been examined. We examined differences in peak immune response and the longitudinal decline of antibodies following SARS-CoV-2 infection and COVID-19 vaccination by serum PFAS levels in a cohort of essential workers in the United States. We measured serum antibodies using an in-house semi-quantitative enzyme-linked immunosorbent assay (ELISA). Two cohorts contributed blood samples following SARS-CoV-2 infection or COVID-19 vaccination. We used linear mixed regression models, adjusting for age, race/ethnicity, gender, presence of chronic conditions, location, and occupation, to estimate differences in immune response with respect to serum PFAS levels. Our study populations included 153 unvaccinated participants that contributed 316 blood draws over a 14-month period following infection, and 860 participants and 2451 blood draws over a 12-month period following vaccination. Higher perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) concentrations were associated with a lower peak antibody response after infection (p = 0.009, 0.031, 0.015). Higher PFOS, perfluorooctanoic acid (PFOA), PFHxS, and PFNA concentrations were associated with slower declines in antibodies over time after infection (p = 0.003, 0.014, 0.026, 0.025). PFOA, PFOS, PFHxS, and PFNA serum concentrations prior to vaccination were not associated with differences in peak antibody response after vaccination or with differences in decline of antibodies over time after vaccination. These results suggest that elevated PFAS may impede potential immune response to SARS-CoV-2 infection by blunting peak antibody levels following infection; the same finding was not observed for immune response to vaccination.

Time-specific impact of mono-benzyl phthalate (MBzP) and perfluorooctanoic acid (PFOA) on breast density of a Chilean adolescent Cohort

IntroductionHigh mammographic density is among the strongest and most established predictors for breast cancer risk. Puberty, the period during which breasts undergo exponential mammary growth, is considered one of the critical stages of breast development for environmental exposures. Benzylbutyl phthalate (BBP) and perfluorooctanoic acid (PFOA) are pervasive endocrine disrupting chemicals that may increase hormone-sensitive cancers. Evaluating the potential impact of BBP and PFOA exposure on pubertal breast density is important to our understanding of early-life environmental influences on breast cancer etiology. ObjectiveTo prospectively assess the effect of biomarker concentrations of monobenzyl phthalate (MBzP) and PFOA at specific pubertal window of susceptibility (WOS) on adolescent breast density. MethodThis study included 376 Chilean girls from the Growth and Obesity Cohort Study with data collection at four timepoints: Tanner breast stages 1 (B1) and 4 (B4), 1- year post- menarche (1YPM) and 2-years post-menarche (2YPM). Dual-energy X-ray absorptiometry was used to assess the absolute fibroglandular volume (FGV) and percent breast density (%FGV) at 2YPM. We used concentrations of PFOA in serum and MBzP in urine as an index of exposure to PFOA and BBP, respectively. Parametric G-formula was used to estimate the time-specific effects of MBzP and PFOA on breast density. The models included body fat percentage as a time-varying confounder and age, birthweight, age at menarche, and maternal education as fixed covariates. ResultsA doubling of serum PFOA concentration at B4 resulted in a non-significant increase in absolute FGV (β:11.25, 95% confidence interval (CI): −0.28, 23.49)), while a doubling of PFOA concentration at 1YPM resulted in a decrease in % FGV (β:-4.61, 95% CI: −7.45, −1.78). We observed no associations between urine MBzP and breast density measures. ConclusionIn this cohort of Latina girls, PFOA serum concentrations corresponded to a decrease in % FGV. No effect was observed between MBzP and breast density measures across pubertal WOS.

Exposure to Perfluoroalkyl Substances and Associations with Pubertal Onset and Serum Reproductive Hormones in a Longitudinal Study of Young Girls in Greater Cincinnati and the San Francisco Bay Area.

Per- and polyfluoroalkyl substances (PFAS), endocrine disrupting chemicals with worldwide exposure, cause changes in mammary gland development in rodents. A few human studies report delay in pubertal events with increasing perfluorooctanoic acid (PFOA) exposure, but to our knowledge none have examined reproductive hormone levels at thelarche. In a cohort of Greater Cincinnati (GC) and San Francisco Bay Area (SFBA) girls recruited at 6-8 years of age, clinical examinations were conducted annually or semiannually with sequential Tanner staging. PFAS concentrations were measured in the first serum sample of 704 girls. In 304 GC girls, estradiol (), estrone (), testosterone (T), and dihydroepiandrosterone sulfate (DHEAS) were measured in serum at four time points around puberty. Relationships between PFAS and age at thelarche, pubarche, and menarche were analyzed using survival and structural equation models. The association between PFAS and reproductive hormones was assessed using linear regression models. Median PFOA serum concentrations in GC (, ) and the SFBA (, ) were higher than in the U.S. In multivariable Cox proportional hazard models [adjusted for race, body mass index (BMI)], increasing serum log-transformed PFOA was associated with a delay in pubarche [; 95% CI: 0.70, 0.99] and menarche (; 95% CI: 0.01, 0.25). Structural equation models indicated a triangular relationship between PFOA, BMI percentile, and the age at the pubertal milestone. Increased PFOA had a statistically significant direct effect of delay on all three milestones, as did BMI. Perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDeA), and 2-(-methyl-perfluorooctane sulfonamido) acetic acid (Me-PFOSA-AcOH) also were associated with later thelarche, and Me-PFOSA-AcOH also with later pubarche. PFOA was inversely associated with DHEAS (), (), and T () concentrations at 6 months prior to puberty. PFAS may delay pubertal onset through the intervening effects on BMI and reproductive hormones. The decreases in DHEAS and associated with PFOA represent biological biomarkers of effect consistent with the delay in onset of puberty. https://doi.org/10.1289/EHP11811.

Temporal decline in serum PFAS concentrations among metropolitan firefighters: Longitudinal study on post-exposure changes following PFAS foam cessation

Firefighters are at a high risk of exposure to per- and polyfluoroalkyl substances (PFAS) due to their frequent use of PFAS-containing foams in training and emergency situations. This longitudinal study aimed to investigate the changes in serum PFAS levels among firefighters following cessation of their exposure to PFAS-containing foams. The study involved 130 firefighters from the South Australian Metropolitan Fire Services (SAMFS), and serum samples were collected at two time points: baseline in 2018–19 and follow-up in 2021–22. Along with the collection of samples, a survey questionnaire was administered to gather information on firefighters' employment and demographic characteristics. Regression models were employed to assess the association between these factors and the outcome variable (annual percentage change in serum PFAS concentration). The results indicated a decline in serum PFAS concentrations over time, with the main contaminants being perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonate (PFHxS), and perfluorooctanoic acid (PFOA). The median and Interquartile Range (IQR) of total PFAS (∑PFAS) concentration reduced from 21.5 ng/ml (IQR: 11 to 53 ng/ml) at baseline to 15 ng/ml (IQR: 8 to 33 ng/ml) at follow-up. On average, there was an annual reduction of 13%, 7%, and 4.4% in serum concentrations of PFOS, PFHxS, and PFOA, respectively. Firefighters under the age of 55, those who used PFAS in the past ten years, or those who had little to no frequency of PFAS exposure in their previous employment, encountered a significantly higher annual percentage reduction (P < 0.05) in both ∑PFAS and PFOS concentrations. None of the independent variables analysed could significantly predict the annual percentage change in PFOA and PFHxS.This study provides evidence for a declining temporal trend in serum PFAS concentrations among metropolitan firefighters following workplace interventions that involved the removal of PFAS-containing foams.

Levels of per- and polyfluoroalkyl substances (PFAS) in Norwegian children stratified by age and sex - Data from the Bergen Growth Study 2.

Due to the persistence, bioaccumulation and potential adverse health effects, there have been restrictions and phase out in the production of certain per- and polyfluoroalkyl substances (PFAS) since the early 2000s. Published serum levels of PFAS during childhood are variable and may reflect the impact of age, sex, sampling year and exposure history. Surveying the concentrations of PFAS in children is vital to provide information regarding exposure during this critical time of development. The aim of the current study was therefore to evaluate serum concentrations of PFAS in Norwegian schoolchildren according to age and sex. Serum samples from 1094 children (645 girls and 449 boys) aged 6-16 years, attending schools in Bergen, Norway, were analyzed for 19 PFAS. The samples were collected in 2016 as part of the Bergen Growth Study 2. Statistical analyses included Student t-test, one-way ANOVA and Spearman's correlation analysis of log-transformed data. Of the 19 PFAS examined, 11 were detected in the serum samples. Perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonic acid (PFHxS) and perfluorononaoic acid (PFNA) were present in all samples with geometric means of 2.67, 1.35, 0.47 and 0.68ng/mL, respectively. In total, 203 children (19%) had PFAS levels above the safety limits set by the German Human Biomonitoring Commission. Significantly higher serum concentrations were found in boys compared to girls for PFOS, PFNA, PFHxS and perfluoroheptanesulfonic acid (PFHpS). Furthermore, serum concentrations of PFOS, PFOA, PFHxS and PFHpS were significantly higher in children under the age of 12 years than in older children. PFAS exposure was widespread in the sample population of Norwegian children analyzed in this study. Approximately one out of five children had PFAS levels above safety limits, indicating a potential risk of negative health effects. The majority of the analyzed PFAS showed higher levels in boys than in girls and decreased serum concentrations with age, which may be explained by changes related to growth and maturation.

Immune response to COVID-19 vaccination in a population with a history of elevated exposure to per- and polyfluoroalkyl substances (PFAS) through drinking water

BackgroundExposure to per- and polyfluoroalkyl substances (PFAS) has been linked to lower vaccine-induced antibody concentrations in children, while data from adults remains limited and equivocal. Characteristics of PFAS exposure and age at vaccination may modify such effects.ObjectiveWe used the mass administration of novel COVID-19 vaccines to test the hypothesis that prior exposure to environmentally-relevant concentrations of PFAS affect antibody response to vaccines in adolescents and adults.MethodsBetween April and June 2021, 226 participants aged 12–90 years with a history of exposure to PFAS in drinking water and who received an mRNA COVID-19 vaccine participated in our prospective cohort study. SARS-CoV-2 anti-spike and anti-nucleocapsid antibodies (IgG) were quantified before the first and second vaccine doses and again at two follow-ups in the following months (up to 103 days post dose 1). Serum PFAS concentrations (n = 39 individual PFAS) were measured once for each participant during baseline, before their first vaccination. The association between PFAS exposure and immune response to vaccination was investigated using linear regression and generalized estimating equation (GEE) models with adjustment for covariates that affect antibody response. PFAS mixture effects were assessed using weighted quantile sum and Bayesian kernel machine regression methods.ResultsThe geometric mean (standard deviation) of perfluorooctane sulfonate and perfluorooctanoic acid serum concentrations in this population was 10.49 (3.22) and 3.90 (4.90) µg/L, respectively. PFAS concentrations were not associated with peak anti-spike antibody response, the initial increase in anti-spike antibody response following vaccination, or the waning over time of the anti-spike antibody response. Neither individual PFAS concentrations nor their evaluation as a mixture was associated with antibody response to mRNA vaccination against COVID-19.Impact statementGiven the importance of understanding vaccine response among populations exposed to environmental contaminants and the current gaps in understanding this relationship outside of early life/childhood vaccinations, our manuscript contributes meaningful data from an adolescent and adult population receiving a novel vaccination.

Estimation of Serum PFOA Concentrations from Drinking and Non-Drinking Water Exposures.

Estimation of Serum PFOA Concentrations from Drinking and Non-Drinking Water Exposures.

Associations between exposure to a mixture of perfluoroalkyl and polyfluoroalkyl substances and age at menarche in adolescent girls utilizing three statistical models

Exposure to perfluoroalkyl and polyfluoroalkyl substances (PFAS) is suggested to interfere with endocrine function and may affect female pubertal development. However, the epidemiological evidence on age at menarche associated with PFAS exposure is still inconsistent. Our objective was to investigate association of serum PFAS concentrations with age at menarche among 12–19 years old girls. We used data on 432 girls from National Health and Nutrition Examination Survey (NHANES) 2007–2012 cycles. NHANES reported serum concentrations of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) as quantified by liquid chromatography tandem mass spectrometry (LC-MS/MS). Age at menarche was self-reported by girls or their guardians. Multivariable linear regression models were applied to estimate the association of individual PFAS exposure with age at menarche. The combined effects of PFAS mixture exposures on age at menarche were assessed using three statistical methods, including Bayesian kernel machine regression (BKMR), weighted quantile sum regression (WQS), and elastic net regression (ENR). In the single-chemical model, girls in the middle tertile of serum PFOA concentration had a lower age at menarche [regression coefficient (β) = -0.73 years, 95% confidence interval (CI): -1.44, -0.01; P = 0.047], compared with those in the lower tertile. Girls in the higher tertile of PFNA exposure were associated with older age at menarche (β = 0.36 years, 95% CI: 0.03, 0.80; P = 0.027), compared with those in the lower tertile. In the multiple-chemical models using BKMR and ENR approaches, higher PFNA exposure was significantly associated with older age at menarche among girls, after adjusting for other PFAS. We found suggestive evidence that higher PFAS mixture exposures may be related to an increase in age at menarche using the BKMR model. In conclusion, exposure to PFNA was associated with the later timing of menarche among girls.

Dietary per- and polyfluoroalkyl substance (PFAS) exposure in adolescents: The HOME study

BackgroundDiet is the primary exposure pathway for per- and polyfluoroalkyl substances (PFAS) in non-occupationally exposed populations. Few studies have examined associations of dietary quality and macronutrient intake with PFAS exposure among US adolescents. ObjectiveTo assess relationships of self-reported dietary quality and macronutrient intake with serum PFAS concentrations in adolescents. MethodsWe used cross-sectional data from 193 Cincinnati, Ohio area adolescents (median age 12.3 years) collected from 2016 to 2019. Using 24-h food recalls completed by adolescents on three separate days, we derived Healthy Eating Index (HEI) scores, HEI components, and macronutrient intake. We measured perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) concentrations in fasting serum samples. Using linear regression, we estimated covariate-adjusted associations between dietary variables and serum PFAS concentrations. ResultsThe median HEI score was 44 and median serum PFOA, PFOS, PFHxS, and PFNA concentrations were 1.3, 2.4, 0.7, and 0.3 ng/mL respectively. In adjusted models, higher total HEI scores, whole fruit and total fruit HEI component scores, and total dietary fiber intake were associated with lower concentrations of all four PFAS. For example, serum PFOA concentrations were 7% lower (95% CI: −15, 2) per standard deviation increase in total HEI score and 9% lower (95% CI: −18, 1) per standard deviation increase in dietary fiber. SignificanceGiven adverse health effects associated with PFAS exposure, it is crucial to understand modifiable exposure pathways. Findings from this study may inform future policy decisions aiming to limit human exposure to PFAS.

Co-variate adjusted associations between serum concentrations of selected perfluoroalkyl substances and urinary concentrations of selected arsenic species.

Data from National Health and Nutrition Examination Survey for 2011-2012 were used to estimate associations of the serum concentrations of perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluoroundecanoic acid (PFUnDA), and 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (Me-PFOSA) with urinary concentrations of total arsenic (UAS), inorganic arsenic (IAS), arsenobetaine (UAB), and dimethyl arsinic acid (UDMA) among US adults aged > = 20years. Concentrations of PFNA were positively associated with all four arsenic variables but statistical significance was observed for IAS only (β = 0.33364, P = 0.04). Concentrations of PFDA were positively associated with UAS (β = 0.20688, P = 0.01), IAS (β = 0.23712, P = 0.02), and UAB (β = 0.26049, P = 0.02). Concentrations of PFUnDA were positively associated with UAS (β = 0.49946, P < 0.01), IAS (β = 0.51782, P < 0.01), UAB (β = 0.62924, P < 0.01), and UDMA (β = 0.26375, P < 0.01). Concentrations of Me-PFOSA with PFAS were inversely associated with every PFAS but statistical significance was observed for UDMA only (β = - 0.05613, P = 0.03). PFOA, PFHxS, and PFOS were, in general, negatively associated with concentrations of all four arsenic variables but without reaching statistical significance. Positive associations of PFDA, PFNA, and PFUnDA with arsenic necessitate investigation about impact of the co-exposure of these PFAS with arsenic and their impact on health. Fluorinated carbon chain length > 8 as opposed to ≤ 8 may have a role in defining associations of PFAS with arsenic.

Cumulative maternal and neonatal effects of combined exposure to a mixture of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) during pregnancy in the Sprague-Dawley rat

Globally, biomonitoring data demonstrate virtually all humans carry residues of multiple per- and polyfluoroalkyl substances (PFAS). Despite pervasive co-exposure, limited mixtures-based in vivo PFAS toxicity research has been conducted. Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) are commonly detected PFAS in human and environmental samples and both produce adverse effects in laboratory animal studies, including maternal and offspring effects when orally administered during pregnancy and lactation. To evaluate the effects of combined exposure to PFOA and PFOS, we orally exposed pregnant Sprague-Dawley rats from gestation day 8 (GD8) to postnatal day 2 (PND2) to PFOA (10–250 mg/kg/d) or PFOS (0.1–5 mg/kg/d) individually to characterize effects and dose response curve parameters, followed by a variable-ratio mixture experiment with a constant dose of PFOS (2 mg/kg/d) mixed with increasing doses of PFOA (3–80 mg/kg/d). The mixture study design was intended to: 1) shift the PFOA dose response curves for endpoints shared with PFOS, 2) allow comparison of dose addition (DA) and response addition (RA) model predictions, 3) conduct relative potency factor (RPF) analysis for multiple endpoints, and 4) avoid overt maternal toxicity. Maternal serum and liver concentrations of PFOA and PFOS were consistent between the individual chemical and mixture experiments. Combined exposure with PFOS significantly shifted the PFOA dose response curves towards effects at lower doses compared to PFOA-only exposure for multiple endpoints and these effects were well predicted by dose addition. For endpoints amenable to mixture model analyses, DA produced equivalent or better estimates of observed data than RA. All endpoints evaluated were accurately predicted by RPF and DA approaches except for maternal gestational weight gain, which produced less-than-additive results in the mixture. Data support the hypothesis of cumulative effects on shared endpoints from PFOA and PFOS co-exposure and dose additive approaches for predictive estimates of mixture effects.

Perfluorinated compounds in adults and their association with fasting glucose and incident diabetes: a prospective cohort study

BackgroundThe endocrine disruption of perfluorinated compounds is an emerging issue. We aimed to examine the association of serum perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) levels with incident diabetes and fasting serum glucose concentration.MethodsThis prospective cohort study was based on an urban-based cohort subpopulation from the Korean Genome and Epidemiology Study. Serum samples (600 µL) were received from 100 participants in the normoglycemic baseline survey (2004–2013), and concentrations of PFOA and PFOS were measured using mass spectrometry. The incidence of diabetes was tracked in the follow-up survey (2012–2016).ResultsThe mean age was 56.4 years (men, 59%). The median serum PFOA and PFOS concentrations were 4.29 ng/mL and 9.44 ng/mL, respectively. PFOA and PFOS concentrations differed according to age, sex, and residential area. After 60 months, 23 patients had diabetes. Log-transformed PFOA (lnPFOA) and log-transformed PFOS (lnPFOS) were significantly higher in those who transitioned to diabetes than in those who did not (both p < 0.05). After multivariate adjustment, lnPFOA (coefficient = 6.98, 95% CI -0.04–14, p = 0.054) and lnPFOS (coefficient = 7.06, 95% CI -0.96–15.08, p = 0.088) predicted increased fasting glucose without statistical significance. In addition, lnPFOA, but not lnPFOS, significantly predicted incident diabetes (HR = 3.98, 95% CI 1.42–11.1, p < 0.01).ConclusionExposure to PFOA and PFOS may have a potential dysglycemic effect. In particular, exposure to PFOA increased the risk of diabetes. Further research with larger sample size is warranted.

Association between perfluoroalkyl substances concentration and bone mineral density in the US adolescents aged 12-19 years in NHANES 2005-2010.

BackgroundReports on the association of perfluoroalkyl substances (PFASs) exposure with adolescent bone health are scarce, and studies have primarily targeted maternal serum.ObjectiveWe evaluated the relationship between autologous serum perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS) and perfluorononanoic acid (PFNA) levels and bone mineral density (BMD) in adolescents.MethodsWe analyzed data from 1228 adolescents aged 12-19 years in the National Health and Nutrition Examination Survey (NHANES) 2005-2010 and used multiple regression analysis to identify the relationship between serum PFOA, PFOS, PFHxS, and PFNA concentrations and total femur, femoral neck, and lumbar spine BMD, in addition to multiple stratified subgroup analyses.ResultsThe mean age of participants was 15 years, males had higher serum PFAS concentrations than females. The results of multiple regression analysis showed that the natural log(ln)-transformed serum PFOA, PFOS, and PFNA concentrations were negatively correlated with total femur, femoral neck, and lumbar spine BMD (all p < 0.05), and ln-PFHxS was positively correlated with total femur and femoral neck BMD (all p< 0.05). In males, ln-PFOA was negatively associated with total femur and lumbar spine BMD (all p< 0.05), ln-PFOS was associated with the reduced total femur, femoral neck, and lumbar spine BMD (all p< 0.05), while ln-PFHxS and ln-PFNA were not observed to correlate with BMD at these three sites. In females, both ln-PFOA and ln-PFOS were negatively correlated with total femur and lumbar spine BMD (all p< 0.05), ln-PFHxS is associated with the increased total femur and femoral neck BMD (all p< 0.05), and ln-PFNA was negatively correlated with total femur and femoral neck BMD (all p< 0.05), most of the associations were confined to females. The associations of ln-PFOS with femoral neck BMD and ln-PFNA with total femur BMD were more significant in those who were overweight/obese and had anemia, respectively (all p for interaction < 0.05).ConclusionsIn this representative sample of US adolescents aged 12-19 years, certain PFAS were associated with lower bone mineral density, and most of the associations were confined to females. The negative effect of PFAS on BMD is more pronounced in those who are overweight/obese and have anemia. However, further studies are needed to confirm this finding.

Associations between serum perfluoroalkyl acid (PFAA) concentrations and health related biomarkers in firefighters

ObjectivesFirefighters who used aqueous film forming foam in the past have experienced elevated exposures to perfluoroalkyl acids (PFAAs). The objective of this study was to examine the associations between clinical chemistry endpoints and serum concentrations of perfluorooctanoic acid (PFOA), perfluorohexane sulfonate (PFHxS), perfluoroheptane sulfonate (PFHpS) and perfluorooctane sulfonate (PFOS) in firefighters. Multiple linear regression was used to assess relationships between PFAA serum concentrations and biochemical markers for cardiovascular disease, kidney-, liver- and thyroid function, in a cross-sectional survey of 783 firefighters with elevated levels of PFHxS, PFHpS and PFOS in relation to the most recently reported levels in the general Australian population. Linear logistic regression was used to assess the odds ratios for selected self-reported health outcomes. Repeated measures linear mixed models were further used to assess relationships between PFAAs and biomarkers for cardiovascular disease and kidney function longitudinally in a subset of the firefighters (n = 130) where serum measurements were available from two timepoints, five years apart. In the cross-sectional analysis, higher levels of all PFAAs were significantly associated with higher levels of biomarkers for cardiovascular disease (total-cholesterol, and LDL-cholesterol). For example, doubling in PFOS serum concentration were associated with increases in total cholesterol (β:0.111, 95% confidence interval (95%CI): 0.026, 0.195 mmol/L) and LDL-cholesterol (β: 0.104, 95%CI:0.03, 0.178 mmol/L). Doubling in PFOA concentration, despite not being elevated in the study population, were additionally positively associated with kidney function marker urate (e.g., β: 0.010, 95%CI; 0.004, 0.016 mmol/L) and thyroid function marker TSH (e.g., β: 0.087, 95%CI: 0.014, 0.161 mIU/L). PFAAs were not associated with any assessed self-reported health conditions. No significant relationships were observed in the longitudinal analysis. Findings support previous studies, particularly on the association between PFAAs and serum lipids.

Risk assessment for PFOA and kidney cancer based on a pooled analysis of two studies.

Perfluorooctanoic acid (PFOA) has been associated with kidney cancer in human studies. We conducted a pooled analysis of two large studies of PFOA and renal cell carcinoma (RCC, the most common type of kidney cancer); one from the National Cancer Institute (NCI) (324 cases and controls), and a second from the C8 Science Panel (103 cases and 511 controls). Serum PFOA levels were estimated a median of 8years before diagnosis. Analyses were conducted via conditional logistic regression. Lifetime risk of kidney cancer per unit serum PFOA concentration and per unit dose were calculated. The 25th, 50th and 75th percentiles of serum PFOA levels were 4.8, 7.3, and 23.9ng/ml for the pooled analysis. The preferred model for the pooled datawas a two-piece linear spline model (knot at 12.5ng/ml serum PFOA); the log odds of RCC increased 0.1349 per 1ng/ml increase in serum PFOA up to the knot (eg, an OR of 2.02 (1.45-2.80) from the median to the knot), and was flat thereafter. The estimated lifetime excess risk (cancer slope factor) with an exposure of 1ng/ml was 0.0018, similar to the excess risk of 0.0026 recently reported by CalEPA based on different methods. Assuming a serum half-life of 2.3years and a distribution volume of 170ml/kg for PFOA, our results are equivalent to 0.0128 per ng/kg/d of PFOA intake. To limit excess lifetime kidney cancer risk to 1/1,000,000, our data suggest a limit of 0.0015ng/L (0.0015 ppt) for PFOA in drinking water, similar to CalEPA's proposed Public Health Goal and the new US EPA Drinking Water Health Advisory. Our results correspond reasonably well with cancer slope factors developed by other investigators using published summary data, and suggest drinking water limits similar to new recommendations by the US EPA.

Physical activity modifies the relation between gestational perfluorooctanoic acid exposure and adolescent cardiometabolic risk

ObjectiveExposure to per- and polyfluoroalkyl substances (PFAS) – endocrine disrupting chemicals – may increase cardiometabolic risk. We evaluated whether adolescent lifestyle factors modified associations between gestational PFAS exposure and cardiometabolic risk using a prospective cohort study. MethodsIn 166 mother-child pairs (HOME Study), we measured concentrations of four PFAS in maternal serum collected during pregnancy. When children were age 12 years, we calculated cardiometabolic risk scores from visceral adiposity area, blood pressure, and fasting serum biomarkers. We assessed adolescent physical activity and Healthy Eating Index scores using the Physical Activity Questionnaire for Older Children (PAQ-C), actigraphy, and 24-h diet recalls. Using multivariable linear regression and weighted quantile sum regression, we examined whether physical activity or diet modified covariate-adjusted associations of PFAS and their mixture with cardiometabolic risk scores. ResultsPhysical activity modified associations between perfluorooctanoic acid (PFOA) and cardiometabolic risk scores. Each doubling of PFOA was associated with worse cardiometabolic risk scores among children with PAQ-C scores < median (β:1.4; 95% CI:0.5, 2.2, n = 82), but not among those with PAQ-C scores ≥ median (β: 0.2; 95% CI: 1.2, 0.7, n = 84) (interaction p-value = 0.01). Associations were most prominent for insulin resistance, leptin-adiponectin ratio, and visceral fat area. We observed results suggesting that physical activity modified the association of PFAS mixture with cardiometabolic risk scores, insulin resistance, and visceral fat area (interaction p-values = 0.17, 0.07, and 0.10, respectively); however, the 95% CIs of the interaction terms included the null value. We observed similar, but attenuated patterns for PFOA and actigraphy-based measures of physical activity. Diet did not modify any associations. Physical activity or diet did not modify associations for other PFAS. ConclusionsChildhood physical activity modified associations of prenatal serum PFOA concentrations with children's cardiometabolic risk in this cohort, indicating that lifestyle interventions may ameliorate the adverse effects of PFOA exposure.