Serum Polyfluoroalkyl Substances Concentrations Research Articles

Serum per- and polyfluoroalkyl substance (PFAS) levels and health-related biomarkers in a pilot study of skiers in New England

BackgroundPer- and polyfluoroalkyl substances (PFAS), synthetic chemicals with adverse health effects, are used extensively in consumer products. Ski waxes, applied to the base of skis, contain up to 100% PFAS by mass, but exposure and health effects are poorly characterized. ObjectivesOur objectives were to quantify serum PFAS concentrations among skiers and explore associations with reported ski wax use and biomarkers of cardiometabolic, thyroid, and immune health. MethodsWe recruited 30 active adult skiers to provide non-fasting blood samples and complete questionnaires. We quantified 18 PFAS using mass spectrometry, and measured serum lipids, thyroid hormones, and immunoglobulins. We explored associations of individual and aggregate measures of serum PFAS with wax use indicators and health biomarkers using multivariable regression models, adjusted for age and gender identity. ResultsNine PFAS (PFBS, PFHpS, PFHxS, Sm-PFOS, n-PFOS, PFDA, PFNA, PFUnDA, n-PFOA) were detected in 100% of participants, and MeFOSAA in 93%. Compared to NHANES, median serum concentrations (ng/ml) were similar, but higher in coaches (e.g., PFOAall: 1.1, PFOAcoaches: 2.7, PFOANHANES: 1.2; PFNAall: 0.5, PFNAcoaches: 1.7, PFNANHANES: 0.4). Factors reflecting wax exposure were positively associated with PFAS: e.g., >10 years as a snow sport athlete, compared to ≤10 years, was associated with 3.2 (95% CI: 0.7, 5.6) ng/ml higher aggregate PFAS, as defined by National Academies of Science, Engineering, and Medicine (NASEM). An IQR (6.3 ng/ml) increase in NASEM PFAS was associated with 32.1 (95% CI: 7.0, 57.2), 35.5 (13.5, 57.5), and 12.8 (0.6, 25.1) mg/dl higher total cholesterol, LDL-C, and sdLDL-C, respectively. DiscussionOur study provides early evidence that recreational skiers, particularly coaches, are exposed to PFAS through ski wax. Several PFAS were associated with higher serum lipids among these physically active adults. Interventions to remove PFAS from fluorinated wax could decrease direct exposure to skiers and reduce PFAS release into the environment.

Serum concentrations of per- and polyfluorinated substances and risk of B-cell non-Hodgkin lymphoma

Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants that are detectable in the serum of most U.S. adults. Some studies of highly-exposed individuals have suggested positive associations between PFAS and B-cell non-Hodgkin lymphoma (B-NHL). To investigate whether associations exist at lower exposure levels, we conducted a nested case-control study investigating serum PFAS concentrations and B-NHL within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We measured pre-diagnostic serum concentrations of five PFAS among 706 cases (age at diagnosis = 55–93 years, median 73 years) and 706 controls individually matched on age at blood draw, sex, self-reported race and ethnicity, study center, and year of blood collection (the median follow-up years = 10). We estimated odds ratios (ORs) and 95 % confidence intervals (CIs) for PFAS concentrations in relation to B-NHL, both overall and for selected histologic subtypes [diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), and marginal zone lymphoma (MZL)] using conditional logistic regression. We found no evidence of a positive association with B-NHL for any of the five PFAS. In analyses of histologic subtypes, perfluorohexane sulfonate (PFHxS) was significantly associated with DLBCL in a model adjusting for all other PFAS (OR for highest vs. lowest quintile = 2.19, 95 % CI = 1.21, 3.95; Ptrend = 0.02), but not in a model without mutual adjustment (OR = 1.37, 95 % CI = 0.82, 2.29; Ptrend = 0.26). We also observed an inverse association between perfluorononanoate and DLBCL (mutually-adjusted OR = 0.83, 95 % CI = 0.69, 0.99 per doubling in concentration), although the association was null among participants with blood drawn prior to 1997 (OR<1997 = 1.00, 95 % CI = 0.82, 1.21; OR≥1997 = 0.65, 95 % CI = 0.53, 0.79; Pinteraction = 0.0003). In conclusion, our findings from a prospective cohort study with PFAS serum concentrations comparable to that of the general population do not support an association with increased risk of B-NHL overall. The suggestive evidence of a positive association between PFHxS and DLBCL warrants further investigation.

Association between family economic situation and serum PFAS concentration in American adults with hypertension and hyperlipemia

Although there is an association between income status and concentration of perfluoroalkyl and polyfluoroalkyl substance (PFAS), the association remains uncertain in patients with hypertension, hyperlipidemia, and comorbidities. Data from the 2013–2016 National Health and Nutrition Examination Survey were analyzed. A total of 2665 adults were included, and the data included participants' serum PFAS (perfluorooctanoic acid [PFOA], perfluorononaic acid, perfluorodecanoic acid, perfluoroundecanoic acid, perfluorohexane sulfonic acid, and perfluorooctane sulfonic acid) levels and selected covariates. Multivariate linear regression models were used to examine the association between the ratio of family income to poverty (PIR) and individual serum PFAS concentrations in the hypertensive and/or hyperlipidemia groups after adjusting for covariates. The potential effects of sex and age on the results were explored using stratified analysis. A mediating effect model was used to explore the mediating effects of body mass index (BMI) and waist circumference on the association results. After adjusting for potential confounders, for hyperlipidemia and comorbidities (hypertension and hyperlipidemia), serum levels of multiple common PFAS increased by 0.09% (95%Confidence interval [CI] 0.02–0.15%) to 0.13% (95%CI 0.08–0.19%) and 0.10% (95%CI 0.02–0.17%) to 0.12% (95%CI 0.06–0.18%), respectively, with each 1% increase in PIR. The covariate model and stratified analyses results suggested the potential effects of different covariates such as age and sex, leading to changes in the statistical significance of the association results. BMI significantly mediated the effect of PIR on PFOA in hyperlipidemia (13%, P < 0.001). Household income in adults with hyperlipidemia and comorbidities positively correlated with serum PFAS concentration in the United States. Obesity played an indispensable mediating role in the association between economic income and PFAS concentration.

(002) PER- AND POLYFLUOROALKYL SUBSTANCES (PFAS) AND FEMALE SEXUAL FUNCTION IN A PRECONCEPTION COHORT

Abstract Introduction Per- and polyfluoroalkyl substances (PFAS) are prevalent environmental chemicals used extensively in consumer and industrial products. Distressing disruptions to sexual function are prevalent in reproductive-aged women, yet its etiology is incompletely characterized. PFAS could plausibly affect sexual function because they interfere with the production, metabolism, and secretion of reproductive hormones and have known neurotoxic properties. To our knowledge, however, no research to date has evaluated associations between PFAS exposure and female sexual function. Objective To evaluate associations between PFAS biomarker concentrations and female sexual function. Methods We used cross-sectional data from the Pregnancy Study Online (PRESTO; n=82), a preconception cohort study of female-identified pregnancy planners living in the United States or Canada, to estimate associations between PFAS biomarker concentrations and female sexual function, measured using 6 select items from the Female Sexual Function Index (FSFI). We summed scores from the FSFI items to create a sexual function score (range=0-30; median in PRESTO=22). Lower scores were indicative of worse sexual function. We measured concentrations of four PFAS (specifically PFOS, PFOA, PFNA, and PFHxS) in serum using isotope-dilution tandem mass spectrometry. We used multivariable linear regression to estimate mean differences in sexual function scores per interquartile range (IQR) increase in PFAS concentrations with 95% confidence intervals (CIs), adjusting for potential confounders. We stratified results by parity (parous vs. nulliparous) to evaluate the potential for effect modification by prior pregnancy, as placental transfer, menstruation, and lactation are known routes of PFAS elimination. Results Median serum PFAS concentrations (ng/mL) were 1.3, 1.1, 0.3, and 0.7 for PFOS, PFOA, PFNA, and PFHxS, respectively. An IQR increase in PFHxS was associated with a 1.4-point decrease (95% CI -2.1, -0.6) in sexual function scores, reflecting a ~5% change. Among parous participants, there was a consistent trend of decreased sexual function scores per IQR increase in PFAS concentrations. The strongest association was observed for PFOS, where an IQR increase in serum concentration was associated with a 4.9-point decrease in sexual function scores (95% CI -9.1, -0.6). Conclusions These preliminary findings indicate that higher serum PFAS concentrations are associated with decreased self-reported female sexual function. Prior research evaluating the relationship between environmental chemical exposures and sexual function have historically focused on male outcomes (e.g., semen quality). These fundings suggest value in expanding research focused on the sexual health consequences of endocrine disrupting chemicals to include female sexual function. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: LAW serves as a consultant to AbbVie, Inc.

Dietary seafood as a potential modifier in the relationship between per- and polyfluoroalkyl substances (PFASs) burden and prediabetes/diabetes: Insights from a nationally representative cross-sectional study

While seafood is recognized for its beneficial effects on glycemic control, concerns over elevated levels of per- and polyfluoroalkyl substances (PFASs) may deter individuals from its consumption. This study aims to elucidate the relationship between seafood intake, PFASs exposure, and the odds of diabetes. Drawing from the China National Human Biomonitoring data (2017–2018), we assessed the impact of PFASs on the prevalence of prediabetes and diabetes across 10851 adults, including 5253 individuals (48.1%) reporting seafood consumption. Notably, seafood consumers exhibited PFASs levels nearly double those of non-consumers. Multinomial logistic regression identified significant positive associations between serum PFASs concentrations and prediabetes (T3 vs. T1: ORPFOA: 1.64 [1.08–2.49], ORPFNA: 1.59 [1.19–2.13], ORPFDA: 1.56 [1.13–2.17], ORPFHxS: 1.58 [1.18–2.12], ORPFHpS: 1.73 [1.24–2.43], ORPFOS: 1.51 [1.15–1.96], OR6:2 Cl-PFESA: 1.58 [1.21–2.07]). Significant positive association were also found between PFHpS, PFOS, and diabetes. RCS curves indicated significant non-linear relationships between log-transformed PFOA, PFUnDA, PFOS, 6:2 Cl-PFESA, and FBG levels. Subgroup analyses revealed that seafood consumption significantly mitigated the associations between PFASs burdens and prediabetes/diabetes. These findings suggest a protective role of dietary seafood against the adverse effects of PFASs exposure on glycemic disorders, offering insights for dietary interventions aimed at mitigating diabetes risks associated with PFASs.

Per- and polyfluoroalkyl substances (PFAS) and fetal growth: A nation-wide register-based study on PFAS in drinking water

BackgroundThere is inconclusive evidence for an association between per- and polyfluoroalkyl substances (PFAS) and fetal growth. ObjectivesWe conducted a nation-wide register-based cohort study to assess the associations of the estimated maternal exposure to the sum (PFAS4) of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorohexane sulfonic acid (PFHxS) with birthweight as well as risk of small- (SGA) and large-for-gestational-age (LGA). Materials and methodsWe included all births in Sweden during 2012–2018 of mothers residing ≥ four years prior to partus in localities served by municipal drinking water where PFAS were measured in raw and drinking water. Using a one-compartment toxicokinetic model we estimated cumulative maternal blood levels of PFAS4 during pregnancy by linking residential history, municipal PFAS water concentration and year-specific background serum PFAS concentrations in Sweden. Individual birth outcomes and covariates were obtained via register linkage. Mean values and 95 % confidence intervals (CI) of β coefficients and odds ratios (OR) were estimated by linear and logistic regressions, respectively. Quantile g-computation regression was conducted to assess the impact of PFAS4 mixture. ResultsAmong the 248,804 singleton newborns included, no overall association was observed for PFAS4 and birthweight or SGA. However, an association was seen for LGA, multivariable-adjusted OR 1.08 (95% CI: 1.01–1.16) when comparing the highest PFAS4 quartile to the lowest. These associations remained for mixture effect approach where all PFAS, except for PFOA, contributed with a positive weight. DiscussionsWe observed an association of the sum of PFAS4 – especially PFOS – with increased risk of LGA, but not with SGA or birthweight. The limitations linked to the exposure assessment still require caution in the interpretation.

Associations between serum perfluoroalkyl and polyfluoroalkyl concentrations and diabetes mellitus in the Korean general population: Insights from the Korean National Environmental Health Survey 2018–2020

AimsRecent epidemiologic research has examined the relationship between perfluoroalkyl and polyfluoroalkyl substances (PFAS) and diabetes mellitus with inconclusive findings. In this cross-sectional study, we aimed to explore the association between serum PFAS concentrations and the prevalence of prediabetes and pre-diagnostic diabetes in the general Korean population as well as the combined effects of exposure to mixed PFAS compounds. MethodsWe analyzed data from participants aged ≥19 years enrolled in the Korean National Environmental Health Survey Cycle 4 (2018–2020). Individuals diagnosed with diabetes were excluded to minimize potential bias. We identified cases of pre-diagnostic diabetes based on the HbA1c level ≥6.5% and prediabetes as HbA1c levels of 5.7–6.49%. Serum concentrations of PFAS, including perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDeA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS), were quantified using high-performance liquid chromatography-tandem mass spectrometry. Survey-weighted logistic regression models were used to assess the relationships between PFAS levels and diabetes risk, adjusting for covariates. Additionally, Bayesian kernel machine regression (BKMR) was used to investigate the combined effects of exposure to mixed PFAS compounds. ResultsIn the study population excluding participants with diagnosed diabetes (n = 2709), the prevalence of pre-diagnostic diabetes and prediabetes was 4.8% and 30.1%, respectively. Significant positive associations were found between serum PFHxS and PFOS quartiles and pre-diagnostic diabetes risk. Likewise, among those without diagnosed or pre-diagnostic diabetes (n = 2579), the highest quartiles of PFDeA, PFHxS, and PFOS and the overall PFAS level were associated with an increased risk of prediabetes compared with the lowest quartiles. BKMR analysis revealed a significant positive association between overall serum PFAS level and prediabetes risk, which was most marked for PFOS. ConclusionsThese findings highlight the potential health implications of PFAS exposure and prediabetes risk. Further research is needed to validate these associations and identify potential mechanistic pathways.

Abstract 840: Serum concentrations of per- and polyfluorinated substances and risk of non-Hodgkin lymphoma

Abstract Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants, some immunotoxic, that are detectable in the serum of most U.S. adults. Some studies of highly-exposed individuals have suggested positive associations between PFAS and non-Hodgkin lymphoma (NHL); however, it is unknown whether associations exist at lower exposure levels that are more common in the general population. To address this knowledge gap, we conducted a nested case-control study investigating serum PFAS concentrations and NHL within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We measured pre-diagnostic serum concentrations (collected between 1993-2001) of five PFAS among 706 cases and 706 controls individually matched on the basis of age at baseline, sex, self-reported race and ethnicity, study center, calendar year of blood collection, and number of prior serum thaws. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for PFAS concentrations in relation to NHL, both overall and for selected histologic subtypes [diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), lymphoplasmacytic lymphoma (LPL), and marginal zone lymphoma (MZL)] using conditional logistic regression. We found no evidence of a positive association with NHL for any of the five PFAS in analyses adjusting for all measured PFAS. In analyses of histologic subtypes, we observed a positive association between perfluorohexane sulfonate (PFHxS) and DLBCL (OR per doubling in concentration=1.27, 95% CI=1.07, 1.50) which remained for cases diagnosed ≥10 years after blood collection (OR=1.34, 95% CI=1.09, 1.64). We also observed inverse associations with PFNA for all subtypes (DLBCL, OR=0.84, 95% CI=0.72, 0.98; FL, OR=0.86, 95% CI=0.69, 1.08; LPL/MZL, OR=0.86, 95% CI=0.66, 1.12), although these associations were null among participants with blood drawn prior to 1997 (DLBCL: OR&amp;lt;1997=0.95, OR≥1997=0.67, Pinteraction=0.001; FL: OR&amp;lt;1997=1.01, OR≥1997=0.77, Pinteraction =0.08; LPL/MZL: OR&amp;lt;1997=1.26, OR≥1997=0.88, Pinteraction =0.03). In conclusion, our findings from a cohort study with PFAS serum concentrations comparable to that of the general population do not support an association with increased risk of NHL overall. The suggestive evidence of a positive association between PFHxS and DLBCL warrants further investigation. Citation Format: Jongeun Rhee, Jani Koponen, Joshua N. Sampson, Alexander P. Keil, Mary H. Ward, Jonathan N. Hofmann, Wen-Yi Huang, Debra T. Silverman, Panu Rantakokko, Mark P. Purdue. Serum concentrations of per- and polyfluorinated substances and risk of non-Hodgkin lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 840.

The association between per-/polyfluoroalkyl substances in serum and thyroid function parameters: A cross-sectional study on teenagers living near a Chinese fluorochemical industrial plant

Thyroid hormones (THs) play an important role in a wide range of crucial biological functions related to growth and development, and thyroid antibodies (TAs) can influence the biosynthesis of THs. Epidemiological studies have indicated that per- and polyfluoroalkyl substances (PFAS) could induce thyroid disruption, but studies on teenagers living in areas with high PFAS exposure are limited. This cross-sectional study focused on 836 teenagers (11– 15 years) living near a Chinese fluorochemical industrial plant. Decreased levels of free thyroxine (FT4, ﹤9.6 pmol/L, abnormal rate = 19.0 %) and elevated levels of free triiodothyronine (FT3, ﹥6.15 pmol/L, abnormal rate = 29.8 %) were observed. Correlations of serum PFAS concentrations and TAs/THs were analyzed. Increased PFOA was identified as a risk factor of decreased FT4 by using unadjusted (OR: 11.346; 95 % CI: 6.029, 21.352, p < 0.001) and adjusted (OR: 12.566; 95 % CI: 6.549, 24.115, p < 0.001) logistic regression models. In addition, significantly negative correlations were found between log10 transformed PFOA and FT4 levels using linear (unadjusted: β = −1.543, 95 % CI: −1.937, −1.148, p < 0.001; adjusted: β = −1.534, 95 % CI: −1.930, −1.137, p < 0.001) and BKMR models. For abnormal FT3, a significantly positive association between PFHxS and FT3 levels was observed in a regression model (unadjusted: β = −0.903, 95 % CI: −1.212, −0.595, p < 0.001; adjusted: β = −0.894, 95 % CI: −1.204, −0.583, p < 0.001), and PFHxS was identified as a risk factor (unadjusted: OR: 4.387; 95 % CI: 2.619, 7.346, p < 0.001; adjusted: OR: 4.527; 95 % CI: 2.665, 7.688, p < 0.001). Sensitivity analyses confirmed the robustness of the above results. This study reported the elevated PFAS exposure and thyroid function of teenagers living near a fluorochemical industrial plant from China.

Comparison of Serum Per- and Polyfluoroalkyl Substances Concentrations in Incumbent and Recruit Firefighters and Longitudinal Assessment in Recruits.

Firefighters are occupationally exposed to per- and polyfluoroalkyl substances (PFAS). This study objective was to compare serum PFAS concentrations in incumbent and recruit firefighters and evaluate temporal trends among recruits. Serum PFAS concentrations were measured in 99 incumbent and 55 recruit firefighters at enrollment in 2015-2016, with follow-up 20 to 37 months later for recruits. Linear and logistic regression and linear mixed-effects models were used for analyses. Fireground exposure impact on PFAS concentrations was investigated using adjusted linear and logistic regression models. Incumbents had lower n-PFOA and PFNA than recruits and most PFAS significantly decreased over time among male recruits. No significant links were found between cumulative fireground exposures and PFAS concentrations. Serum PFAS concentrations were not increased in incumbent firefighters compared with recruits and were not associated with cumulative fireground exposures.

Trends in Serum Per- and Polyfluoroalkyl Substance (PFAS) Concentrations in Teenagers and Adults, 1999–2018 NHANES

Some types of per- and poly-fluoroalkyl substances (PFAS) have been banned over the last two decades, but millions of Americans continue to have exposure to the compounds through drinking water and consumer products. Therefore, understanding the changes in serum PFAS concentrations after their limited use is necessary to protect public health. In this study, we evaluated trends of serum PFAS compounds (PFOS, PFOA, PFHxS, PFDA, and PFNA) to determine their distribution among the United States general population. We analyzed serum concentrations of PFAS measured from random subsamples of the National Health and Nutrition Examination Survey (NHANES) participants. The study results demonstrated that demographic factors such as race/ethnicity, age, and sex may influence the levels of serum PFAS over time. Adults, males, Asians, Non-Hispanic Blacks, and Non-Hispanic Whites had high risks of exposure to the selected PFAS. Overall, serum PFAS levels declined continuously in the studied population from 1999 to 2018. Among the studied population, PFOS and PFDA were the most and least prevalent PFAS in blood serum, respectively. Serum levels of PFDA, PFOA, and PFHxS showed upward trends in at least one racial/ethnic group after 2016, which underscores the need for continuous biomonitoring of PFAS levels in humans and the environment.

THU342 Per And Polyfluoroalkyl Substances And Prevalence Of Diabetes Mellitus In Korean Adults

Abstract Disclosure: S. Kim: None. Objectives: Recent epidemiologic research has studied the relationship between Per- and polyfluoroalkyl substances (PFAS) and diabetes mellitus (DM), yet the findings have been inconsistent. We examined the association between serum PFAS concentrations and the prevalence of diabetes in the Korean general population. Methods: We analyzed the data of 2,993 participants aged ≥ aged 19 years who participated in the Korean National Environmental Health Survey (KoNEHS) Cycle 4 (2018-2020). Serum concentrations of 5 PFAS [perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDeA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS)] were quantified using using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Individuals with DM were identified by the presence of one or more of the following conditions: (1) self-reported diabetes; (2) use of a glucose-lowering medication; (3) hemoglobin A1c ≥6.5%. Multiple logistic regression models were used to examine the associations between PFAS concentrations and DM after adjusting for age, sex, central obesity, education levels, smoking status, alcohol consumption, physical activity, and frequency of delivery food consumption. Bayesian kernel machine regression (BKMR) was used to investigate the independent and combined relationship between PFAS exposure and DM prevalence. Results: The prevalence of DM was 11.8%. The odds ratios (95% confidence intervals) of DM in the highest quartile relative to the lowest were 0.85 (0.56, 1.32) for PFOA, 1.39 (0.87, 2.23) for PFNA, 0.95 (0.63, 1.43) for PFDeA, 1.52 (1.01, 2.35) for PFHsS, 1.26 (0.77, 2.05) for PFOS and 1.01 (0.66, 1.55) for the sum of PFAS. According to the BKMR model results, PFNA and PFHxS were positively associated with an increased risk of DM, while PFOA and PFDeA were negatively associated. The risk of DM appeared to rise in correlation with the PFAS mixture quartile, but the association was statistically insignificant. Conclusions: Different associations between PFAS concentrations and DM were observed according to the PFAS isomers. Further studies are needed to clarify the mechanism of action of different PFAS isomers on the development of DM. Presentation: Thursday, June 15, 2023

Per- and polyfluoroalkyl substances in umbilical cord serum and body mass index trajectories from birth to age 10 years: Findings from a longitudinal birth cohort (SMBCS)

BackgroundPrenatal exposure to per- and polyfluoroalkyl substances (PFAS) has been linked to low birth weight but higher childhood weight and obesity. However, little is known regarding the associations between PFAS exposure and dynamic body mass index (BMI) trajectories, particularly from birth through preadolescence. ObjectiveTo evaluate the associations of cord serum PFAS concentrations with BMI trajectories from birth to age 10 years and longitudinal BMI in different periods. MethodsBased on 887 mother–child pairs in the longitudinal prospective birth cohort, we measured 12 PFAS congeners in cord serum and calculated BMI with anthropometric indicators at 9 follow-up time points from birth to age 10 years. The BMI trajectories were identified using group-based trajectory model (GBTM). To estimate the associations of cord serum PFAS levels with BMI trajectories and longitudinal changes in BMI, logistic regression models, linear mixed models, Bayesian kernel machine regression, and quantile-based g-computation models (QGC) were used. ResultsThe median concentrations of 10 PFAS congeners included in statistical analysis ranged from 0.047 to 3.623 μg/L. Two BMI trajectory classes were identified by GBTM, characterized by high group and low group. In logistic regression models, five PFAS congeners (PFBA, PFHpA, PFHxS, PFHpS, and PFDoDA) were associated with the higher probability of being in high BMI trajectory group (odds ratio, OR: 1.21 to 1.74, p < 0.05). Meanwhile, higher PFAS mixture were related to elevated odds for the high group in both BKMR models and QGC models, with PFHpA and PFHpS being the two most important drivers jointly. In the sex-stratified analysis, the positive associations remained significant exclusively among males. In the longitudinal analysis, PFUnDA and PFDoDA were associated with increased BMI from birth to age 10 years. Furthermore, PFBS and PFHpA were negatively related to BMI throughout infancy and toddlerhood (from birth to age 3 years), whereas PFDoDA confirmed a positive association with mid-childhood (from age 6 to 10 years) BMI. ConclusionsPrenatal PFAS exposure was positively associated with BMI trajectories from birth to preadolescence and longitudinal BMI in various periods. Future research could use better trajectory modeling strategies to shape more complete growth trajectories and explore the relationship between BMI trajectories and adulthood health.

Serum concentrations of per- and polyfluoroalkyl substances and risk of renal cell carcinoma in the Multiethnic Cohort Study

Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent organic pollutants detectable in the serum of most U.S. adults. We previously reported a positive association between serum perfluorooctanoate (PFOA) concentrations and risk of renal cell carcinoma (RCC) within the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, comprising predominantly White individuals enrolled in 1993–2001. To extend our investigations to a larger and more racially and ethnically diverse population, we conducted a nested case-control study of serum PFAS concentrations and RCC within the Multiethnic Cohort Study. We measured pre-diagnostic serum concentrations of nine PFAS among 428 RCC cases and 428 individually matched controls. We estimated odds ratios (ORs) and 95 % confidence intervals (CIs) for risk of RCC in relation to each PFAS using conditional logistic regression, adjusting for RCC risk factors and other PFAS. PFOA was not associated with RCC risk overall [doubling in serum concentration, ORcontinuous = 0.89 (95 %CI = 0.67, 1.18)]. However, we observed suggestive positive associations among White participants [2.12 (0.87, 5.18)] and among participants who had blood drawn before 2002 [1.49 (0.77, 2.87)]. Furthermore, higher perfluorononanoate (PFNA) concentration was associated with increased risk of RCC overall [fourth vs. first quartile, OR = 1.84 (0.97, 3.50), Ptrend = 0.04; ORcontinuous = 1.29 (0.97, 1.71)], with the strongest association observed among African American participants [ORcontinuous = 3.69 (1.33, 10.25)], followed by Native Hawaiian [2.24 (0.70, 7.19)] and White [1.98 (0.92, 4.25)] participants. Most other PFAS were not associated with RCC. While PFOA was not associated with RCC risk overall in this racially and ethnically diverse population, the positive associations observed among White participants and those with sera collected before 2002 are consistent with previous PLCO findings. Our study also provided new evidence of a positive association between PFNA and RCC risk that was strongest in African American participants. These findings highlight the need for additional epidemiologic research investigating PFAS exposures and RCC in large racially and ethnically diverse populations.

Factors associated with per- and polyfluoroalkyl substances (PFAS) serum concentrations in residents of New Hanover County, North Carolina: The GenX exposure study

In 2017, people living in New Hanover County, North Carolina, learned that for ∼40 years they were unknowingly exposed to per- and polyfluoroalkyl substances (PFAS) through drinking water sourced by the Cape Fear River. Using data from the GenX Exposure Study, which measured serum PFAS levels in county residents, we aimed to understand questionnaire-measured factors associated with serum PFAS levels. Because most residents were served by the same municipal water source, we focused on surrogate factors of drinking water exposure that may contribute to variability in PFAS levels. Our analysis included 335 participants aged 6 and older. We included seven chemicals detected in ≥75% of the study population: four well-studied perfluoroalkyl acids (PFOA, PFOS, PFNA, PFHxS) and three understudied fluoroethers (Nafion byproduct 2, PFO4DA, PFO5DoA). For each PFAS, we evaluated associations of variables with serum PFAS levels adjusting for key demographic characteristics. Additionally, we developed predictive models for each PFAS. We used years of residence in the lower Cape Fear Region as a surrogate for water consumption. Duration of drinking water exposure was associated with higher serum levels of all seven PFAS. Drinking municipal water treated by home filters or other sources of water (non-city) were associated with lower PFAS concentrations for all seven PFAS compared to drinking municipal water without additional filtration. Males had higher levels of well-studied PFAS, but there was no difference for fluoroethers. For six PFAS, the predictive models explained ≥30% of the variance in serum PFAS levels. While some factors were significantly associated with levels of individual PFAS, their relative importance to overall prediction was low, such as microwave popcorn consumption. Consistently, water consumption-related variables were important for both the association and predictive investigations. These analyses provide additional evidence that drinking water is a primary source for serum PFAS concentrations among New Hanover County residents.

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.

Per- and Polyfluoroalkyl Substances (PFAS) and Lipid Trajectories in Women 45-56 Years of Age: The Study of Women's Health Across the Nation.

Per- and polyfluoroalkyl substances (PFAS) are associated with less favorable blood lipid profiles in epidemiological studies. However, little is known about the potential role of PFAS in longitudinal changes in lipids among midlife women even though women become more susceptible to metabolic alterations during the menopausal transition. To examine associations of serum PFAS concentrations with longitudinal trajectories of blood total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides in midlife women undergoing menopausal transition. The sample included 1,130 women from the Study of Women's Health Across the Nation 45-56 y of age at baseline (1999-2000). We measured serum PFAS concentrations including linear perfluorooctanoic acid (n-PFOA), perfluorononanoic acid (PFNA), linear and branched perfluorooctanesulfonic acid (n-PFOS and Sm-PFOS, respectively), and perfluorohexanesulfonic acid (PFHxS) at baseline. We used k-means clustering to identify subgroups with different patterns of PFAS mixture. Blood lipids were measured annually or biannually through 2016 with an average follow-up of 14.8 y. We identified longitudinal trajectories of each lipid using latent class growth models. We used multinomial log-linear models adjusted for covariates to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of lipid trajectory classes by PFAS and their mixtures. Three distinct trajectories (low, middle, high) of total, LDL, and HDL cholesterol and two distinct trajectories (low and high) of triglycerides were identified. n-PFOS, Sm-PFOS, and PFHxS were positively associated with total and LDL cholesterol trajectories. n-PFOS was inversely associated with triglycerides trajectories. PFAS mixtures (high vs. low) showed positive associations with total and LDL cholesterol trajectories (high vs. low), showing ORs (95% CIs) of 1.69 (95% CI: 1.36, 2.12) and 1.79 (95% CI: 1.44, 2.22), respectively. Concentrations of serum PFAS were positively associated with trajectories of total and LDL cholesterol, providing a line of evidence supporting adverse effects of PFAS on lipid homeostasis. https://doi.org/10.1289/EHP12351.

A Nested Case-Control Study of Serum Per- and Polyfluoroalkyl Substances and Testicular Germ Cell Tumors among U.S. Air Force Servicemen.

Per- and polyfluoroalkyl substances (PFAS) are a component of firefighting foams used at military installations. Although high PFAS exposures have been related to cancer risks among civilian populations, the effects for military personnel are unclear. We investigated associations between serum PFAS concentrations and testicular germ cell tumors (TGCT) among U.S. Air Force servicemen. This nested case-control study involved active-duty Air Force servicemen with sera from the Department of Defense Serum Repository. We selected 530 cases and 530 controls individually matched on birth date, race and ethnicity, year entered the service, and year of sample collection, with prediagnostic serum samples collected between 1988 and 2017. A second prediagnostic sample, collected a median of 4 y after the first, was selected for 187 case-control pairs. Seven PFAS were quantified using isotope-dilution tandem mass spectrometry. Odds ratios (ORs) and 95% confidence intervals (CIs) from conditional logistic regression adjusting for military grade, number of deployments, and, in some models, other PFAS, estimated associations between PFAS concentrations (categorized using quartiles among controls) and TGCT. Elevated concentrations of some PFAS were observed for military employment in firefighting [perfluorooctanesulfonic acid (PFOS), perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid] and service at a base with high PFAS concentrations in drinking water (PFHxS). Elevated PFOS concentrations in the second sample were positively associated with TGCT [OR for fourth vs. first quartile , 95% CI: 1.1, 6.4; ], including after adjustment for other PFAS (, 95% CI: 1.4, 15.1; ). Associations with PFOS in the first/only samples were weak and not statistically significant. Elevated concentrations of perfluorononanoic acid were inversely associated with TGCT, whereas results were null for other PFAS. We identified service-related predictors of PFAS concentrations and increased TGCT relative risks with elevated PFOS concentrations among Air Force servicemen. These findings warrant further investigation in other populations and military service branches. https://doi.org/10.1289/EHP12603.

PFAS levels in paired drinking water and serum samples collected from an exposed community in Central North Carolina

The community of Pittsboro, North Carolina has been documented to have extensive per- and polyfluoroalkyl substances (PFAS) contamination in its drinking water source, the Haw River, over the last 20 years. However, a detailed exposure assessment has never been conducted. In this study, we sought to characterize the PFAS in paired drinking water and blood samples collected from a small cohort of Pittsboro residents (n = 49). Drinking water and serum from blood were collected from adults in late 2019 and early 2020 and were analyzed to quantify 13 PFAS analytes. In order to explore potential health effects of PFAS exposure, serum was further analyzed for clinical chemistry endpoints that could be potentially associated with PFAS (e.g., cholesterol, liver function biomarkers). PFAS were detected in all serum samples, and some serum PFAS concentrations were 2 to 4 times higher than the median U.S. serum concentrations reported in the general U.S. population. Of the 13 PFAS in drinking water, perfluorohexanoic acid (PFHxA) was measured at the highest concentrations. PFAS levels in the current drinking water were not associated with current serum PFAS, suggesting that the serum PFAS in this cohort likely reflects historical exposure to PFAS with long half-lives (e.g., PFOS and PFOA). However, one PFAS with a shorter half-life (PFHxA) was observed to increase in serum, reflecting the temporal variability of PFHxA in river and drinking water. Statistical analyses indicated that serum PFOA and PFHxS were positively associated with total cholesterol and non-HDL cholesterol. No serum PFAS was associated with HDL cholesterol. In the clinical chemistry analyses, serum PFHxA was found to be negatively associated with electrolytes and liver enzymes (e.g., AST and ALT), and serum PFOS was found to be positively associated with the ratio of blood urea nitrogen to creatinine (BUN:Cre). While small in size, this study revealed extensive exposure to PFAS in Pittsboro and associations with clinical blood markers, suggesting potential health impacts in community residents.

Domestic Dogs and Horses as Sentinels of Per- and Polyfluoroalkyl Substance Exposure and Associated Health Biomarkers in Gray's Creek North Carolina.

Central North Carolina (NC) is highly contaminated with per- and polyfluoroalkyl substances (PFAS), in part due to local fluorochemical production. Little is known about the exposure profiles and long-term health impacts for humans and animals that live in nearby communities. In this study, serum PFAS concentrations were determined using liquid chromatography high-resolution mass spectrometry and diagnostic clinical chemistry endpoints were assessed for 31 dogs and 32 horses that reside in Gray's Creek NC at households with documented PFAS contamination in their drinking water. PFAS were detected in every sample, with 12 of the 20 PFAS detected in ≥50% of samples from each species. The average total PFAS concentrations in horses were lower compared to dogs who had higher concentrations of PFOS (dogs 2.9 ng/mL; horses 1.8 ng/mL), PFHxS (dogs 1.43 ng/mL, horses < LOD), and PFOA (dogs 0.37 ng/mL; horses 0.10 ng/mL). Regression analysis highlighted alkaline phosphatase, glucose, and globulin proteins in dogs and gamma glutamyl transferase in horses as potential biomarkers associated with PFAS exposure. Overall, the results of this study support the utility of companion animal and livestock species as sentinels of PFAS exposure differences inside and outside of the home. As in humans, renal and hepatic health in domestic animals may be sensitive to long-term PFAS exposures.