Search

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., (© 2024. The Author(s).)

Background: Although recent in vitro experimental results have raised the question of whether maternal exposure to per- and polyfluoroalkyl substances (PFAS) may be a potential environmental risk factor for chromosomal abnormalities, epidemiological studies investigating these associations are lacking., Objectives: This study examined whether prenatal PFAS exposure is associated with a higher prevalence of chromosomal abnormalities among offspring., Methods: We used data from the Japan Environment and Children's Study, a nationwide birth cohort study, and employed logistic regression models to examine the associations between maternal plasma PFAS concentrations in the first trimester and the diagnosis of chromosomal abnormalities in all births (artificial abortions, miscarriages, stillbirths, and live births) up to 2 years of age. In addition, we examined associations with mixtures of PFAS using multipollutant models., Results: The final sample consisted of 24,724 births with singleton pregnancies, of which 44 confirmed cases of chromosomal abnormalities were identified (prevalence: 17.8/10,000 births). When examined individually, exposure to perfluorononanoic acid (PFNA) and perfluorooctane sulfonic acid (PFOS) showed positive associations with any chromosomal abnormalities with age-adjusted odds ratios of 1.81 (95% CI: 1.26, 2.61) and 2.08 (95% CI: 1.41, 3.07) per doubling in concentration, respectively. These associations remained significant after Bonferroni correction, although they did not reach the adjusted significance threshold in certain sensitivity analyses. Furthermore, the doubling in all PFAS included as a mixture was associated with chromosomal abnormalities, indicating an age-adjusted odds ratio of 2.25 (95% CI: 1.34, 3.80), with PFOS as the predominant contributor, followed by PFNA, perfluoroundecanoic acid (PFUnA), and perfluorooctanoic acid (PFOA)., Discussion: The study findings suggested a potential association between maternal exposure to PFAS, particularly PFOS, and chromosomal abnormalities in offspring. However, the results should be interpreted cautiously, because selection bias arising from the recruitment of women in early pregnancy may explain the associations. https://doi.org/10.1289/EHP13617.

Introduction: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are widely used in the manufacture of fluoropolymers. We evaluated biochemical and haematological effects of three PFAS, serum perfluorooctanoic acid (PFOA), ADV, and cC 6 O 4 in workers of a fluoropolymer company., Methods: Using data (2013-2022), we fitted random intercept regression models adjusted for several covariates and reciprocal adjustment between the three PFAS., Results: We analysed data of 814 workers (698 men, 116 women), 607 from the chemical plant, 207 from the research centre, for a total of 4912 blood samples (2065 with all three PFAS measured). Median levels of PFOA and ADV were 21.3 and 120 μg/L. Most (65.5%) cC 6 O 4 measurements were below the limits of quantification (which varied over time from 5 to 0.1 μg/L). For PFOA, we observed positive associations with total cholesterol (+1.1% increase per ln(PFOA) increase) and apolipoprotein B (+1.4%) and negative associations with alkaline phosphatase (-1.5%); suggestive associations were also found with RBC (-0.4%), IgA (-1.5%), IgM (-1.4%). ADV was positively associated with total and LDL cholesterol (+1.0% and +1.6% per ln(ADV) increase), apolipoprotein B (+1.0%), GGT (+2.1%), IgM (+1.4%), and WBC (+1.5%) and negatively associated with direct bilirubin (-2.3%) and alpha-2-globulins (-0.7%); suggestive associations were found for indirect bilirubin (-2.0%), oestradiol (-2.1%), ad CRP (+6.0%). For samples with detectable cC 6 O 4 levels we observed higher values of ALP (+2.3%), proteins (+0.5%), IgG (+0.7%) and platelets (+1.6%) and suggestively increased total bilirubin (+3.9%), RBC (+0.6%), and oestradiol (+5.8%). Some associations (total cholesterol, apolipoprotein B, WBC, total bilirubin, and alkaline phosphatase showed reverse time trends in parallel with the strong decrease of serum PFOA and ADV over the study period., Discussion: We found associations of serum PFOA and ADV with lipid metabolism, liver function, and immunoglobulins. The reverse time trends of some endpoints in parallel with decrease of serum PFOA and ADV reinforce causal interpretation of results. cC 6 O 4 showed a different pattern of associations., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: Many studies have reported that prenatal exposure to Per- and Polyfluoroalkyl Substances (PFASs) can disrupt immune function. However, little is known about the effects of PFASs on immune molecules. The study analyzed the association between prenatal exposure to mixed and single PFASs and plasma immune molecules in three-year-old children., Methods: Ten PFASs were measured in umbilical cord serum, while peripheral blood samples were collected at age three to measure immune molecules. Associations between exposure to individual and combined PFASs and immune molecules were analyzed using Generalized Linear Models and Weighted Quantile Sum (WQS) regression., Results: (1) Interleukin-4 (IL-4) increased by 23.85% (95% CI:2.99,48.94) with each doubling of Perfluorooctanoic Acid (PFOA), and Interleukin-6 (IL-6) increased by 39.07% (95%CI:4.06,85.86) with Perfluorotridecanoic Acid (PFTrDA). Elevated PFOA and Perfluorononanoic Acid (PFNA) were correlated with increases of 34.06% (95% CI: 6.41, 70.28) and 24.41% (95% CI: 0.99, 53.27) in Eotaxin-3, respectively. Additionally, the doubling of Perfluorohexane Sulfonic Acid (PFHxS) was associated with a 9.51% decrease in Periostin (95% CI: -17.84, -0.33). (2) The WQS analysis revealed that mixed PFASs were associated with increased IL-6 (β = 0.37, 95%CI:0.04,0.69), mainly driven by PFTrDA, PFNA, and 8:2 Chlorinated Perfluoroethyl Sulfonamide (8:2 Cl-PFESA). Moreover, mixed PFASs were linked to an increase in Eotaxin-3 (β = 0.32, 95% CI: 0.09,0.55), primarily influenced by PFOA, PFTrDA, and Perfluorododecanoic Acid (PFDoDA)., Conclusions: Prenatal PFASs exposure significantly alters the levels of immune molecules in three-year-old children, highlighting the importance of understanding environmental impacts on early immune development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Per- and polyfluoroalkyl substances (PFAS) constitutes a group of highly persistent man-made substances. Recent evidence indicates that PFAS negatively impact the immune system. However, it remains unclear how different PFAS are associated with alterations in circulating leukocyte subpopulations. More detailed knowledge of such potential associations can provide better understanding into mechanisms of PFAS immunotoxicity in humans. In this exploratory study, associations of serum levels of common PFAS (perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS)) and immune cell profiles of peripheral blood mononuclear cells, both with and without immunostimulation, were investigated. High-dimensional single cell analysis by mass cytometry was done on blood leukocytes from fifty participants in the Norwegian human biomonitoring EuroMix study. Different PFAS were associated with changes in various subpopulations of natural killer (NK), T helper (Th), and cytotoxic T (Tc) cells. Broadly, PFAS concentrations were related to increased frequencies of NK cells and activated subpopulations of NK cells. Additionally, increased levels of activated T helper memory cell subpopulations point to Th2/Th17 and Treg-like skewed profiles. Finally, PFAS concentrations were associated with decreased frequencies of T cytotoxic cell subpopulations with CXCR3 + effector memory (EM) phenotypes. Several of these observations point to biologically plausible mechanisms that may contribute to explaining the epidemiological reports of immunosuppression by PFAS. Our results suggest that PFAS exposures even at relatively low levels are associated with changes in immune cell subpopulations, a finding which should be explored more thoroughly in a larger cohort. Additionally, causal relationships should be confirmed in experimental studies. Overall, this study demonstrates the strength of profiling by mass cytometry in revealing detailed changes in immune cells at a single cell level., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hubert Dirven reports financial support was provided by the European Union., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Epidemiologic studies have reported the relationships between perfluoroalkyl substances (PFASs) and breast cancer incidence, yet the underlying mechanisms are not well understood. This study aimed to elucidate the mediation role of mitochondrial DNA copy number (mtDNAcn) in the relationships between PFASs exposure and breast cancer risk. We conducted a case-cohort study within the Dongfeng-Tongji cohort, involving 226 incident breast cancer cases and a random sub-cohort (n = 990). Their plasma concentrations of six PFASs [including perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroheptanoic acid (PFHpA), perfluorooctane sulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS)], and peripheral blood levels of mtDNAcn, were detected at baseline by using ultraperformance liquid chromatography-tandem mass spectrometry and quantitative real-time PCR, respectively. Linear regression and Barlow-weighted Cox models were employed separately to assess the relationships of mtDNAcn with PFASs and breast cancer risk. Mediation analysis was further conducted to quantify the mediating effects of mtDNAcn on PFAS-breast cancer relationships. We observed increased blood mtDNAcn levels among participants with the highest PFNA and PFHpA exposure [Q4 vs. Q1, β(95%CI) = 0.092(0.022, 0.162) and 0.091(0.022, 0.160), respectively], while no significant associations were observed of PFOA, PFDA, PFOS, or PFHxS with mtDNAcn. Compared to participants within the lowest quartile subgroup of mtDNAcn, those with the highest mtDNAcn levels exhibited a significantly increased risk of breast cancer and postmenopausal breast cancer [Q4 vs. Q1, HR(95%CI) = 3.34(1.80, 6.20) and 3.71(1.89, 7.31)]. Furthermore, mtDNAcn could mediate 14.6 % of the PFHpA-breast cancer relationship [Indirect effect, HR(95%CI) = 1.02(1.00, 1.05)]. Our study unveiled the relationships of PFNA and the short-chain PFHpA with mtDNAcn and the mediation role of mtDNAcn in the PFHpA-breast cancer association. These findings provided insights into the potential biological mechanisms linking PFASs to breast cancer risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Per- and polyfluoroalkyl substance (PFAS) exposure and cardiovascular disease are controversial. We aimed to assess the association between serum PFAS exposure and cardiovascular health (CVH) in U.S. adults., Methods: We analyzed serum PFAS concentration data of U.S. adults reported in the National Health and Nutrition Examination Survey (NHANES) study (2005-2018). We employed two weighted logistic regression models and a restricted cubic spline (RCS) to examine the association between each PFAS and impaired CVH (defined as moderate and low CVH). Quantile g-computation (Qgcomp) and weighted quantile sum (WQS) analysis were used to estimate the effects of mixed exposures to PFASs on impaired CVH., Results: PFAS were associated with an increased risk of impaired CVH (OR PFNA : 1.40, 95% CI: 1.09, 1.80; OR PFOA : 1.44, 95% CI: 1.10, 1.88; OR PFOS : 1.62, 95% CI: 1.25, 2.11). PFOA and PFOS exhibited nonlinear relationships with impaired CVH. Significant interactions were observed for impaired CVH between race/ethnicity and PFHxS ( p  = 0.02), marital status and PFOA ( p  = 0.03), and both marital status and race/ethnicity with PFOS ( p  = 0.01 and p = 0.02, respectively). Analysis via WQS and Qgcomp revealed that the mixture of PFAS was positively associated with an increased risk of impaired CVH., Conclusion: PFNA, PFOA, and PFOS exposure are associated with an increased risk of impaired CVH in U.S. adults. Race/ethnicity and marital status may influence CVH. Reducing PFAS exposure could alleviate the burden of disease associated with impaired CVH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zong, Wang, Wang, Wang, Jiang, Sun, Zong and Li.)

We synthesized the epidemiologic evidence on the associations between per- and polyfluoroalkyl substances (PFAS) exposure and breast cancer risk. Our systematic review and meta-analysis included 18 and 11 articles, respectively, covering studies up to February 2023. The summary relative risks (RRs) estimated by random-effects meta-analyses did not support an association between PFAS and overall breast cancer risk (eg, a natural log (ln)-unit increase in serum/plasma concentrations [ng/mL] for perfluorooctanoate [PFOA] RR = 0.95; 95% CI, 0.77-1.18; perfluorooctane sulfonate [PFOS] RR = 0.98; 95% CI, 0.87-1.11). However, when limiting to studies that assessed exposures prior to a breast cancer diagnosis, we observed a positive association with PFOA (a ln-unit increase, RR = 1.16; 95% CI, 0.96-1.40). We also observed some possible heterogeneous associations by tumor estrogen and progesterone receptor status among postmenopausal breast cancer cases. No meaningful changes were observed after excluding the studies with high risk of bias (Tier 3). Based on the evaluation tool developed by the National Toxicology Program, given the heterogeneity across studies and the variability in timing of exposure measurements, the epidemiologic evidence needed to determine the association between PFAS exposure and breast cancer remains inadequate. Our findings support the need for future studies with improved study designs to determine this association., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2024.)

The National Academies of Sciences, Engineering, and Medicine recommends per- and polyfluoroalkyl substance (PFAS) blood testing for patients with risk of elevated exposure, and the Agency for Toxic Substances and Disease Registry (ATSDR) suggests PFAS blood testing based on exposure. Barriers to PFAS blood testing include cost, access to labs, and evolving laboratory methods. We quantify water and serum PFAS levels among a highly-exposed cohort in an area with groundwater contaminated by historical agricultural biosolid application. We compare the gold standard PFAS serum test with a commercial test and results from a one-compartment toxicokinetic model. Participants were adults (n = 30) whose household (n = 19) water had levels of the sum of six PFAS > 500 ng/L. Serum PFAS were measured using liquid chromatography-tandem mass spectrometry. Demographic and water consumption data were collected via telephone. Serum PFAS results from the commercial test were accessed via medical record. Statistical analysis included descriptive statistics and bivariate plots of serum levels. Perfluorohexanoic acid, perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorobutanesulfonic acid, perfluorohexanesulfonic acid (PFHxS), and perfluorooctanesulfonic acid (PFOS) were detected in 19 wells, and PFHpA, PFOA, PFNA, perfluorodecanoic acid, perfluoroundecanoic acid, PFHxS, and PFOS were detected in at least 19 participants' serum. In well water, PFOA and PFOS levels had geometric means (GMs) of 1749 ng/L (geometric standard deviation [GSD] 2.4) and 887 ng/L (GSD 19.7), respectively. In serum, PFOA and PFOS had GMs of 116.2 µg/L (GSD 13.5) and 58.3 µg/L (GSD 13.8), respectively. Our results are comparable with and had a wider mix of PFAS than other high-exposure cohorts. There was good agreement between the commercial and gold standard tests for PFOA, PFNA, and PFHxS, and mixed agreement between the gold standard test and modeled predictions, suggesting water-based toxicokinetic models of serum PFAS may be inadequate for assessing exposure in this population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Human exposure to per- and polyfluoroalkyl substances (PFASs) has received considerable attention, particularly in pregnant women because of their dramatic changes in physiological status and dietary patterns. Predicting internal PFAS exposure in pregnant women, based on external and relevant parameters, has not been investigated. Here, machine learning (ML) models were developed to predict the serum concentrations of PFOA and PFOS in a large population of 588 pregnant participants. Dietary exposure characteristics, demographic parameters, and in particular, serum fatty acid (FA) data were used for the model development. The fitting results showed that the inclusion of FAs as covariates significantly improved the performance of the ML models, with the random forest (RF) model having the best predictive performance for PFOA (R 2  = 0.33, MAE = 1.51 ng/mL, and RMSE = 1.89 ng/mL) and PFOS (R 2  = 0.12, MAE = 2.65 ng/mL, and RMSE = 3.37 ng/mL). The feature importance analysis revealed that serum FAs greatly affected PFOA concentration in the pregnant women, with saturated FAs being associated with decreased PFOA levels and unsaturated FAs with increased levels. Comparison with one-compartment pharmacokinetic model further demonstrated the advantage of the ML models in predicting PFAS exposure in pregnant women. Our models correlate for the first time blood chemical concentrations with human FA status using ML, introducing a novel perspective on predicting PFAS levels in pregnant women. This study provides valuable insights concerning internal exposure of PFASs generated from external exposure, and contributes to risk assessment and management in pregnant populations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aim: To explore the effect of mixed exposure to per- and polyfluoroalkyl substances (PFAS) on metabolic syndrome (MetS)., Methods: This cross-sectional study used data from the Korean National Environmental Health Survey Cycle 4 (2018-2020). The serum concentrations of five PFAS (perfluorooctanoic acid [PFOA], perfluorooctanesulfonic acid [PFOS], perfluorohexanesulfonic acid, perfluorononanoic acid [PFNA], and perfluorodecanoic acid [PFDeA]) were measured, and the relative potency factor approach was employed for the mixture of PFAS (Cmix) assessment. MetS was diagnosed if the patient satisfied three of five criteria: central obesity, elevated triglycerides, reduced high-density lipoprotein cholesterol, elevated blood pressure (BP), and elevated glycated hemoglobin (HbA1c). Age, sex, smoking, drinking, and exercise status were considered as covariates. The risk of MetS for single and mixed exposure to PFAS was analyzed using binomial regression and Bayesian kernel machine regression (BKMR)., Results: A total of 2984 (male:female = 1:1.3; age range, 19-80 years) adults were enrolled. The prevalence of MetS was 45.6%. Each PFAS and Cmix levels were higher in participants with MetS than in those without MetS. Cmix increased the risk of elevated BP and HbA1c, and eventually MetS (odds ratio [OR] = 2.00, 95% confidence interval [CI] 1.11-3.60 per log 10 Cmix; OR = 1.57, 95% CI 1.07-2.31 in the highest quartile of Cmix [Q4] vs. the lowest [Q1]). Sex-specific analyses revealed that the impact of Cmix was valid in females but not in males (Cmix Q4 vs. Q1: OR = 1.01, 95% CI 0.57-1.8 in males; OR = 2.30, 95% CI 1.38-3.84 in females). In the BKMR analysis, mixed exposure to PFAS dose-dependently increased the risk of MetS, particularly in females. Among single exposures, PFNA contributed significantly to the cumulative effect., Conclusion: Mixed exposure to PFAS was associated with a higher risk of MetS in females. Further studies on potential health concerns associated with PFAS mixtures are warranted., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: Perfluoroalkyl and polyfluoroalkyl substance (PFAS) has endocrine-disrupting properties and may affect blood pressure. Endogenous hormones also play a crucial role in the progression of hypertension. However, their interaction with hypertension remains to be explored., Methods: This study included 10 794 adults aged ≥18 years from the China National Human Biomonitoring program. Weighted multiple logistic regression and linear regression were used to examine the associations of serum PFAS with hypertension, diastolic blood pressure, and systolic blood pressure. Joint effects of PFAS mixtures on hypertension, diastolic blood pressure, and systolic blood pressure were evaluated using quantile-based g-computation. Additive and multiplicative interactions were used to assess the role of PFAS with testosterone and estradiol on hypertension., Results: The prevalence of hypertension in Chinese adults was 35.50%. Comparing the fourth quartile with the first quartile, odds ratio (95% CI) of hypertension were 1.53 (1.13-2.09) for perfluorononanoic acid, 1.40 (1.03-1.91) for perfluorodecanoic acid, 1.34 (1.02-1.78) for perfluoroheptane sulfonic acid, and 1.46 (1.07-1.99) for perfluorooctane sulfonic acid. Moreover, PFAS mixtures, with perfluorononanoic acid contributing the most, were positively associated with hypertension, diastolic blood pressure, and systolic blood pressure. PFAS and endogenous hormones had an antagonistic interaction in hypertension. For example, the relative excess risk ratio, attributable proportion, and synergy index for perfluorononanoic acid and estradiol were -3.61 (-4.68 to -2.53), -1.65 (-2.59 to -0.71), and 0.25 (0.13-0.47), respectively., Conclusions: Perfluorononanoic acid, perfluorodecanoic acid, perfluoroheptane sulfonic acid, perfluorooctane sulfonic acid, and PFAS mixtures showed positive associations with hypertension, systolic blood pressure, and diastolic blood pressure. Positive associations of PFAS with hypertension might be attenuated by increased levels of endogenous sex hormones., Competing Interests: None.

The increasing global prevalence of gestational diabetes mellitus (GDM) has been hypothesized to be associated with maternal exposure to environmental chemicals. Here, among 420 women participating in the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort study, we examined associations between GDM and second trimester blood or urine concentrations of endocrine disrupting chemicals (EDCs): bisphenol-A (BPA), bisphenol-S (BPS), twelve phthalate metabolites, eight perfluoroalkyl acids (PFAAs), and eleven trace elements. Fifteen (3.57%) of the women were diagnosed with GDM, and associations between the environmental chemical exposures and GDM diagnosis were examined using multiple logistic and LASSO regression analyses in single- and multi-chemical exposure models, respectively. In single chemical exposure models, BPA and mercury were associated with increased odds of GDM, while a significant inverse association was observed for zinc. Double-LASSO regression analysis selected mercury (AOR: 1.51, CI: 1.12-2.02), zinc (AOR: 0.017, CI: 0.0005-0.56), and perfluoroundecanoic acid (PFUnA), a PFAAs, (AOR: 0.43, CI: 0.19-0.94) as the best predictors of GDM. The combined data for this Canadian cohort suggest that second trimester blood mercury was a robust predictor of GDM diagnosis, whereas blood zinc and PFUnA were protective factors. Research into mechanisms that underlie the associations between mercury, zinc, PFUnA, and the development of GDM is needed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Cardiovascular diseases (CVDs) are one of the major causes of death globally. In addition to traditional risk factors such as unhealthy lifestyles (smoking, obesity, sedentary) and genetics, common environmental exposures, including persistent environmental contaminants, may also influence CVD risk. Per- and polyfluoroalkyl substances (PFASs) are a class of highly fluorinated chemicals used in household consumer and industrial products known to persist in our environment for years, causing health concerns that are now linked to endocrine disruptions and related outcomes in women, including interference of the cardiovascular and reproductive systems. In postmenopausal women, higher levels of PFAS are observed than in premenopausal women due to the cessation of menstruation, which is crucial for PFAS excretion. Because of these findings, we explored the association between perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and perfluorobutanesulfonic acid in postmenopausal women from our previously established CVD study. We used liquid chromatography with tandem mass spectrometry, supported by machine learning approaches, and the detection and quantification of serum metabolites and proteins. Here, we show that PFOS can be a good predictor of coronary artery disease, whereas PFOA can be an intermediate predictor of coronary microvascular disease. We also found that the PFAS levels in our study are significantly associated with inflammation-related proteins. Our findings may provide new insight into the potential mechanisms underlying the PFAS-induced risk of CVDs in this population. This study shows that exposure to PFOA and PFOS is associated with an increased risk of cardiovascular disease in postmenopausal women. PFOS and PFOA levels correlate with amino acids and proteins related to inflammation. These circulating biomarkers contribute to the etiology of CVD and potentially implicate a mechanistic relationship between PFAS exposure and increased risk of cardiovascular events in this population., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Diet is an important source of perfluoroalkyl and polyfluoroalkyl substance (PFAS) exposure, and the dietary inflammatory index (DII) is a tool used to assess the inflammatory potential of an individual's diet. However, limited research has explored the association between the DII and PFAS exposure in humans. This study is the first to analyze the association between the five PFASs and DII using the National Health and Nutrition Examination Survey (NHANES) 2007-2018 database. Additionally, we assessed the interaction between the DII and PFASs regarding oxidative stress and inflammatory markers, including alkaline phosphatase, albumin, neutrophil count, lymphocyte count, total bilirubin, and serum iron based on a previous study. A series of covariates were included in the analysis to reduce the confounding bias. The study included 7773 and 5933 participants based on the different models. The DII was significantly associated with serum perfluorooctanoic acid, perfluorononanoic acid, perfluorooctane sulfonic acid, and sum-PFAS. Some of the food parameters used to calculate the DII also showed associations with special PFAS serum concentrations. Specifically, dietary fiber, n-3 polyunsaturated fatty acids, energy intake, and vitamin D were associated with more than three PFASs. Higher DII levels in participants were linked to a more significant association between bilirubin (the interaction P -value is not significant), alkaline phosphatase, serum iron, neutrophil counts, and some PFASs. In conclusion, this study clarified the association between the three PFASs and DII, highlighting the diverse effects of PFASs on oxidative stress and inflammatory markers across different DII levels.

Per- and polyfluoroalkyl substances (PFAS) are related to various adverse health outcomes, and food is a common source of PFAS exposure. Dietary sources of PFAS have not been adequately explored among U.S. pregnant individuals. We examined associations of dietary factors during pregnancy with PFAS concentrations in maternal plasma and human milk in the New Hampshire Birth Cohort Study. PFAS concentrations, including perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), and perfluorodecanoate (PFDA), were measured in maternal plasma collected at ∼28 gestational weeks and human milk collected at ∼6 postpartum weeks. Sociodemographic, lifestyle and reproductive factors were collected from prenatal questionnaires and diet from food frequency questionnaires at ∼28 gestational weeks. We used adaptive elastic net (AENET) to identify important dietary variables for PFAS concentrations. We used multivariable linear regression to assess associations of dietary variables selected by AENET models with PFAS concentrations. Models were adjusted for sociodemographic, lifestyle, and reproductive factors, as well as gestational week of blood sample collection (plasma PFAS), postpartum week of milk sample collection (milk PFAS), and enrollment year. A higher intake of fish/seafood, eggs, coffee, or white rice during pregnancy was associated with higher plasma or milk PFAS concentrations. For example, every 1 standard deviation (SD) servings/day increase in egg intake during pregnancy was associated with 4.4 % (95 % CI: 0.6, 8.4), 3.3 % (0.1, 6.7), and 10.3 % (5.6, 15.2) higher plasma PFOS, PFOA, and PFDA concentrations respectively. Similarly, every 1 SD servings/day increase in white rice intake during pregnancy was associated with 7.5 % (95 % CI: -0.2, 15.8) and 12.4 % (4.8, 20.5) greater milk PFOS and PFOA concentrations, respectively. Our study suggests that certain dietary factors during pregnancy may contribute to higher PFAS concentrations in maternal plasma and human milk, which could inform interventions to reduce PFAS exposure for both birthing people and offspring., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Per- and polyfluoroalkyl substance (PFAS) exposures may negatively impact bone mineral accrual, but little is known about potential mitigators of this relation. We assessed whether associations of PFAS and their mixture with bone mineral content (BMC) in adolescence were modified by diet and physical activity., Methods: We included 197 adolescents enrolled in a prospective pregnancy and birth cohort in Cincinnati, Ohio (2003-2006). At age 12 years, we collected serum for PFAS measurements and used dual-energy x-ray absorptiometry to measure BMC. We calculated dietary calcium intake and Health Eating Index (HEI) scores from repeated 24-h dietary recalls, physical activity scores using the Physical Activity Questionnaire for Older Children (PAQ-C), and average moderate to vigorous physical activity (MVPA) based on accelerometry. We estimated covariate-adjusted differences in BMC z-scores per interquartile range (IQR) increase of individual PFAS concentrations using linear regression and per simultaneous IQR increase in all four PFAS using g-computation. We evaluated effect measure modification (EMM) using interaction terms between each modifier and PFAS., Results: Higher serum perfluorooctanoic acid, perfluorooctanesulfonic acid, and perfluorononanoic acid concentrations and the PFAS mixture were associated with lower BMC z-scores. An IQR increase in all PFAS was associated with a 0.27 (-0.54, 0.01) lower distal radius BMC z-score. Associations with lower BMC were generally stronger among adolescents classified as < median for calcium intake, HEI scores, or MVPA compared to those ≥ median. The difference in distal radius BMC z-score per IQR increase in all PFAS was -0.38 (-0.72, -0.04) for those with

Background: Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals linked to adverse pregnancy outcomes. Although their underlying biological mechanisms are not fully understood, evidence suggests PFAS may disrupt endocrine functions and contribute to oxidative stress (OS) and inflammation., Objective: We examined associations between early pregnancy PFAS exposure and OS biomarkers, exploring potential effect modifications by fetal sex and maternal race., Methods: We used data from 469 LIFECODES participants with measured plasma PFAS (median 10 weeks gestation) and repeated measures (median 10, 18, 26, and 35 weeks gestation) of urinary OS biomarkers [8-iso-prostaglandin-F2α (8-isoprostane) and 8-hydroxydeoxyguanosine (8-OHdG)]. Protein damage biomarkers (chlorotyrosine, dityrosine, and nitrotyrosine) were additionally measured in plasma from a subset (N = 167) during the third visit. Associations between each PFAS and OS biomarkers were examined using linear mixed-effects models and multivariable linear regressions, adjusting for potential confounders, including maternal age, race, education level, pre-pregnancy BMI, insurance status, and parity. Effect modifications were evaluated by including an interaction term between each PFAS and fetal sex or maternal race in the models., Results: We observed significant positive associations between PFOS and 8-isoprostane, with a 9.68% increase in 8-isoprostane levels (95% CI: 0.10%, 20.18%) per interquartile range increase in PFOS. In contrast, PFUA was negatively associated [9.32% (95% CI: -17.68%, -0.11%)], while there were suggestive positive associations for MPAH and PFOA with 8-isoprostane. The associations of several PFAS with 8-OHdG varied by fetal sex, showing generally positive trends in women who delivered females, but negative or null in those who delivered males. No significant effect modification by maternal race was observed., Conclusions: This study provides evidence linking PFAS exposure to OS during pregnancy, with potential sex-specific effects of certain PFAS on 8-OHdG. Further research should explore additional OS/inflammatory biomarkers and assess the modifying effects of dietary and behavioral patterns across diverse populations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The presence of perfluoroalkyl and polyfluoroalkyl substances (PFAS) in various everyday products has raised concerns about their potential impact on prostate health. This study aimed to investigate the effects of different types of PFAS on prostate health, including PFDeA, PFOA, PFOS, PFHxS, and PFNA. To assess the relationship between PFAS exposure and prostate injury, machine learning algorithms were employed to analyze prostate-specific antigen (PSA) metrics. The analysis revealed a linear and positive dose-dependent association between PFOS and the ratio of free PSA to total PSA (f/tPSA). Non-linear dose-response relationships were observed between the other four types of PFAS and the f/tPSA ratio. Additionally, the analysis showed a positive association between the mixture of PFAS and prostate hyperplasia, with PFNA having the highest impact followed by PFOS. These findings suggest that elevated serum levels of PFDeA, PFOA, PFOS, and PFNA are linked to prostate hyperplasia. Therefore, this study utilized advanced machine learning techniques to uncover potential hazardous effects of PFAS exposure on prostate health, specifically the positive association between PFAS and prostate hyperplasia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Previous studies reported that exposures to per- and polyfluoroalkyl substances (PFAS), largely in higher exposed populations, were associated with elevated risk of polycystic ovary syndrome (PCOS). However, studies evaluating PCOS risk in populations with lower background exposures to PFAS are limited. This study aimed to examine the associations between serum PFAS concentrations and PCOS risk among women attending a U.S. academic fertility clinic during 2005-2019. A total of 502 females who sought fertility evaluation and assisted reproduction treatments were included. Nine PFAS were quantified in non-fasting serum samples collected at study entry. Diagnosis of PCOS was based on the Rotterdam criteria. We used logistic regression to examine the odds ratio (OR) of PCOS in relation to individual PFAS concentrations (continuous and by tertiles) and quantile g-computation (QGC) and Bayesian Kernel Machine Regression (BKMR) to examine the joint associations of PFAS mixture with PCOS. Most participants were White and had a graduate degree or higher. Per doubling of serum perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) concentrations were associated with higher odds of PCOS [OR (95%CI): 1.70 (1.06, 2.81) and 1.45 (1.02, 2.08) for PFOS and PFHxS respectively]. There was a dose-response relationship of PFOS with PCOS risk (p of trend by PFOS tertiles = 0.07). Both QGC and BKMR identified PFOS as the most important contributor among the mixture to PCOS risk. No clear joint effects were found for other PFAS or PFAS mixtures on PCOS risk. Our findings are consistent with existing evidence in populations with higher background PFAS concentrations and highlight the adverse effects of PFAS exposure on reproductive health. Findings can inform public health measures and clinical care to protect populations vulnerable to PCOS, in part, due to environmental exposures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Per- and polyfluoroalkyl substances (PFAS) constitute a group of synthetic chemicals extensively utilized across various commonplace products. PFAS are known to have various toxic effects on human health. The relationship between PFAS exposure and erythrocytes has been a subject of interest in epidemiological research, but so far, only limited cross-sectional studies have investigated. Additionally, the role of erythrocyte related nutrition indicators on PFAS-induced changes in erythrograms has not been explored. To fill these knowledge gaps, we launched a longitudinal study over a decade, tracking 502 adolescents and young adults aged 12 to 30 from the YOung TAiwanese Cohort (YOTA). Our analysis encompassed 11 types of plasma PFAS, as well as erythrograms and serum levels of ferritin, transferrin saturation, vitamin B12, and folate. Our examination unveiled positive associations between specific average levels of PFAS compounds, including linear perfluorooctanoic acid (PFOA), branched perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS), and transferrin saturation. Furthermore, linear PFOA and both linear and branched PFOS were negatively correlated with vitamin B12 levels. Specifically, we observed that the average linear PFOA demonstrated positive correlations with mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH), while average PFNA also exhibited positive associations with hemoglobin (Hb) and hematocrit (Hct) in a multiple linear regression model. Subsequent analysis revealed noteworthy interactions between vitamin B12 and PFNA, as well as folate and PFNA, in the context of their impact on Hb, Hct, and PFNA relationships. Additionally, an interaction with transferrin saturation was identified in the correlation between Hct and PFNA. These findings suggest a plausible link between PFAS exposure and erythrograms among young populations, underscoring the potential involvement of iron status, vitamin B12, and folate in this association. Further studies are imperative to elucidate the precise effects of PFAS on erythrocyte in human subjects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent, potentially carcinogenic chemicals. Previous studies investigating PFAS exposure and prostate cancer yielded mixed findings. We aimed to investigate associations between PFAS exposure and incident prostate cancer in a large cohort of U.S. men, overall and by selected demographic, lifestyle, and medical-related characteristics., Methods: We conducted a case-cohort study among Cancer Prevention Study-II LifeLink Cohort participants who, at baseline (1998-2001), had serum specimens collected and no prior cancer diagnosis. The study included all men diagnosed with prostate cancer (n = 1610) during follow-up (baseline-June 30, 2015) and a random sub-cohort of 500 men. PFAS concentrations [perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorooctanoic acid (PFOA)] were measured in stored serum specimens. We used multivariable Cox proportional hazards models to estimate associations between PFAS concentrations and prostate cancer, overall and by selected characteristics (grade, stage, family history, age, education, smoking status, and alcohol consumption)., Results: Prostate cancer hazards were slightly higher among men with concentrations in the highest (Q4) vs lowest quartile (Q1) for PFHxS [hazard ratio (HR) (95% CI): 1.18 (0.88-1.59)] and PFOS [HR (95% CI): 1.18 (0.89-1.58)], but not for PFNA or PFOA. However, we observed heterogeneous associations by age, family history of prostate cancer (PFHxS), alcohol consumption (PFHxS), and education (PFNA). For example, no meaningful associations were observed among men aged <70 years at serum collection, but among men aged ≥70 years, HRs (95% CIs) comparing Q4 to Q1 were PFHxS 1.54 (1.02-2.31) and PFOS 1.62 (1.08-2.44). No meaningful heterogeneity in associations were observed by tumor grade or stage., Conclusions: Our findings do not clearly support an association between the PFAS considered and prostate cancer. However, positive associations observed in some subgroups, and consistently positive associations observed for PFHxS warrant further investigation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Background: In mechanistic and preliminary human studies, prenatal exposure to per- and polyfluoroalkyl substances (PFAS) is associated with oxidative stress, a potential contributor to maternal liver disease. Bilirubin is an endogenous antioxidant abundant in the liver that may serve as a physiological modulator of oxidative stress in pregnant people. Hence, our objective was to estimate the association between repeated measures of PFAS and bilirubin during pregnancy., Methods: The study population included 332 participants in the Atlanta African American Maternal-Child Cohort between 2014 and 2020. Serum samples were collected up to two times (early pregnancy: 6-18 gestational weeks; late pregnancy: 21-36 gestational weeks) for the measurement of perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and total bilirubin. We analyzed single PFAS with linear mixed effect regression and a mixture of the four PFAS with quantile g-computation. Models were repeated with a multiplicative interaction term to explore effect modification by study visit., Results: Overall, PFHxS was positively associated with bilirubin (β = 0.08, 95 % CI = 0.01, 0.15). We also found during late pregnancy, there was a positive association of PFHxS and the PFAS mixture with bilirubin (β = 0.12, 95 % CI = 0.02, 0.22; ψ = 0.19, 95 % CI = 0.03, 0.34, respectively). Finally, study visit modified the PFOA-bilirubin association (interaction p-value = 0.09), which was greater during early pregnancy (β = 0.08, 95 % CI = 0.01, 0.15)., Conclusion: In a prospective cohort of pregnant African Americans, an increase in PFOA, PFHxS, and the PFAS mixture was associated with an increase in bilirubin. Our results suggest that, depending on pregnancy stage, prenatal PFAS exposure disrupts the maternal liver antioxidant capacity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Per- and polyfluoroalkyl substances (PFAS) are fluorinated organic compounds used in a variety of consumer products and industrial applications that persist in the environment, bioaccumulate in biological tissues, and can have adverse effects on human health, especially in vulnerable populations. In this study, we focused on PFAS exposures in residents of senior care facilities. To investigate relationships between indoor, personal, and internal PFAS exposures, we analyzed 19 PFAS in matched samples of dust collected from the residents' bedrooms, and wristbands and serum collected from the residents. The median ∑PFAS concentrations (the sum of all PFAS detected in the samples) measured in dust, wristbands, and serum were 120 ng/g, 0.05 ng/g, and 4.0 ng/mL, respectively. The most abundant compounds in serum were linear- and branched-perfluorooctane sulfonic acid (L-PFOS and B-PFOS, respectively) at medians of 1.7 ng/mL and 0.83 ng/mL, respectively, followed by the linear perfluorooctanoic acid (L-PFOA) found at a median concentration of 0.59 ng/mL. Overall, these three PFAS comprised 80 % of the serum ∑PFAS concentrations. A similar pattern was observed in dust with L-PFOS and L-PFOA found as the most abundant PFAS (median concentrations of 13 and 7.8 ng/g, respectively), with the overall contribution of 50 % to the ∑PFAS concentration. Only L-PFOA was found in wristbands at a median concentration of 0.02 ng/g. Significant correlations were found between the concentrations of several PFAS in dust and serum, and in dust and wristbands, suggesting that the indoor environment could be a significant contributor to the personal and internal PFAS exposures in seniors. Our findings demonstrate that residents of assisted living facilities are widely exposed to PFAS, with several PFAS found in blood of each study participant and in the assisted living environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Few methods have been used to characterize repeatedly measured biomarkers of chemical mixtures. We applied latent profile analysis (LPA) to serum concentrations of 4 perfluoroalkyl and polyfluoroalkyl substances (PFAS) measured at 4 time points from gestation to age 12 years. We evaluated the relationships between profiles and z scores of height, body mass index, fat mass index, and lean body mass index at age 12 years (n = 218). We compared LPA findings with an alternative approach for cumulative PFAS mixtures using g-computation to estimate the effect of simultaneously increasing the area under the receiver operating characteristic curve (AUC) for all PFAS. We identified 2 profiles: a higher PFAS profile (35% of sample) and a lower PFAS profile (relative to each other), based on their average PFAS concentrations at all time points. The higher PFAS profile had generally lower z scores for all outcomes, with somewhat larger effects for males, though all 95% CIs crossed the null. For example, the higher PFAS profile was associated with a 0.50-unit lower (β = -0.50; 95% CI, -1.07 to 0.08) BMI z score among males but not among females (β = 0.04; 95% CI, -0.45 to 0.54). We observed similar patterns with AUCs. We found that a higher childhood PFAS profile and higher cumulative PFAS mixtures may be associated with altered growth in early adolescence. This article is part of a Special Collection on Environmental Epidemiology., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Per- and polyfluoroalkyl substances (PFASs) have potential carcinogenicity, immunotoxicity, and hepatotoxicity. Research has been conducted on PFAS exposure in people to discuss their potential health effects, excluding lung cancer. In this study, we recruited participants (n = 282) with lung cancer from Heilongjiang Province, northeast China. The PFAS concentrations were measured in their serum to fill the data gap of exposure, and relationships were explored in levels between PFASs and clinical indicators of tumor, immune and liver function. Ten PFASs were found in over 80 % of samples and their total concentrations were 5.27-152 ng/mL, with the highest level for perfluorooctanesulfonate (median: 12.4 ng/mL). Long-chain PFASs were the main congeners and their median concentration (20.5 ng/mL) was nearly three times to that of short-chain PFASs (7.61 ng/mL). Significantly higher concentrations of perfluorobutanoic acid, perfluorononanoic acid and perfluorohexanesulfonate were found in males than in females (p < 0.05). Serum levels of neuro-specific enolase were positively associated with perfluoropentanoic acid in all participants and were negatively associated with perfluorononanesulfonate in females (p < 0.05, multiple linear regression models). Exposure to PFAS mixture was significantly positively associated with the lymphocytic absolute value (difference: 0.224, 95% CI: 0.018, 0.470; p < 0.05, quantile g-computation models) and serum total bilirubin (difference: 2.177, 95% CI: 0.0335, 4.33; p < 0.05). Moreover, PFAS exposure can affect γ-glutamyl transpeptidase through several immune markers (p < 0.05, mediating test). Our results suggest that exposure to certain PFASs could interfere with clinical indicators in lung cancer patients. To our knowledge, this is the first study to detect serum PFAS occurrence and check their associations with clinical indicators in lung cancer patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Per- and polyfluoroalkyl substances (PFAS) are man-made chemicals that are slow to break down in the environment and widely detected in humans. Epidemiological evidence suggests that prenatal exposure to perfluorooctanoic acid (PFOA), a legacy PFAS, is linked to gestational hypertension and preeclampsia. However, the relationship between other PFAS, which are structurally similar, and these outcomes remains largely understudied, despite biologic plausibility. Here, we examined associations between serum PFAS mixtures in relation to hypertensive disorders of pregnancy within a birth cohort of African Americans., Methods: Participants in the present study were enrolled in the Atlanta African American Maternal-Child cohort between 2014 and 2020 (n = 513). Serum samples collected between 8 and 14 weeks gestation were analyzed for four PFAS. Logistic regression was used to assess associations between individual natural log transformed PFAS and specific hypertensive disorders of pregnancy (preeclampsia, gestational hypertension), while quantile g-computation was used to estimate mixture effects. Preeclampsia and gestational hypertension were treated as separate outcomes in individual models. All models were adjusted for maternal education, maternal age, early pregnancy body mass index, parity, and any alcohol, tobacco, or marijuana use., Results: The geometric mean of PFOS and PFHxS was slightly lower among those with preeclampsia relative to those without a hypertensive disorder (e.g., geometric mean for PFOS was 1.89 and 1.94, respectively). Serum concentrations of PFAS were not strongly associated with gestational hypertension or preeclampsia in single pollutant or mixture models. For example, using quantile g-computation, a simultaneous one quartile increase in all PFAS was not associated with odds of gestational hypertension (odds ratio = 0.86, 95% CI = 0.60, 1.23), relative to those without a hypertensive disorder of pregnancy., Conclusions: In this birth cohort of African Americans, there was no association between serum PFAS measured in early pregnancy and hypertensive disorders of pregnancy, which may be reflective of the fairly low PFAS levels in our study population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aims: Recent 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., Methods: We 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., Results: In 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., Conclusions: These 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., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest pertaining to this study., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background/aims: Pregnant women are exposed to persistent environmental contaminants, including per- and polyfluoroalkyl substances (PFAS) that disrupt thyroid function. However, it is unclear if PFAS alter maternal sex-steroid hormone levels, which support pregnancy health and fetal development., Methods: In Illinois women with relatively high socioeconomic status (n = 460), we quantified perfluorononanoic (PFNA), perfluorooctane sulfonic (PFOS), perfluorooctanoic (PFOA), methyl-perfluorooctane sulfonamide acetic acid, perfluorohexanesulphonic (PFHxS), perfluorodecanoic (PFDeA), and perfluoroundecanoic (PFUdA) acid concentrations in fasting serum samples at median 17 weeks gestation, along with plasma progesterone, testosterone, and estradiol. We evaluated covariate-adjusted associations of ln-transformed hormones with each ln-transformed PFAS individually using linear regression and with the PFAS mixture using quantile-based g-computation (QGComp)., Results: Interquartile range (IQR) increases in PFOS were associated with higher progesterone (%Δ 3.0; 95%CI: -0.6, 6.6) and estradiol (%Δ: 8.1; 95%CI: 2.2, 14.4) levels. Additionally, PFHxS was positively associated with testosterone (%Δ: 10.2; 95%CI: 4.0, 16.7), whereas both PFDeA and PFUdA were inversely associated with testosterone (%Δ: -5.7; 95%CI: -10.3, -0.8, and %Δ: -4.1; 95%CI: -7.6, -0.4, respectively). The IQR-standardized PFAS mixture was not associated with progesterone (%Δ: 1.6; 95%CI: -5.8, 9.2), due equal partial positive (%Δ: 9.2; driven by PFOA) and negative (%Δ: -7.4; driven by PFOS) mixture associations. Similarly, the mixture was not associated with testosterone (%Δ: 5.3; 95%CI: -9.0, 20.1), due to similar partial positive (%Δ: 23.6; driven by PFHxS) and negative (%Δ: -17.4; driven by PFDeA) mixture associations. However, we observed a slightly stronger partial positive (%Δ: 25.6; driven by PFOS and PFUdA) than negative (%Δ: -16.3; driven by PFOA) association resulting in an overall non-significant positive trend between the mixture and estradiol (%Δ: 8.5; 95%CI: -3.7, 20.9)., Conclusion: PFAS mixture modeled using QGComp was not associated with maternal sex-steroid hormones due to potential opposing effects of certain PFAS. Additional prospective studies could corroborate these findings., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Objective: The aim was to evaluate the possible association between some endocrine disruptive chemicals and thyroid cancer (TC) in an Italian case-control cohort., Methods: We enrolled 112 TC patients and 112 sex- and age-matched controls without known thyroid diseases. Per- and poly-fluoroalkyl substances (PFAS), poly-chlorinated biphenyls (PCBs), and dichlorodiphenyltrichloroethane (4,4'-DDT and 4,4'-DDE) were measured in the serum by liquid or gas chromatography-mass spectrometry. Unconditional logistic regression, Bayesan kernel machine regression and weighted quantile sum models were used to estimate the association between TC and pollutants' levels, considered individually or as mixture. BRAFV600E mutation was assessed by standard methods., Results: The detection of perfluorodecanoic acid (PFDA) was positively correlated to TC (OR = 2.03, 95% CI: 1.10-3.75, P = 0.02), while a negative association was found with perfluorohexanesulfonic acid (PFHxS) levels (OR = 0.63, 95% CI: 0.41-0.98, P = 0.04). Moreover, perfluorononanoic acid (PFNA) was positively associated with the presence of thyroiditis, while PFHxS and perfluorooctane sulfonic acid (PFOS) with higher levels of presurgical thyroid-stimulating hormone (TSH). PFHxS, PFOS, PFNA, and PFDA were correlated with less aggressive TC, while poly-chlorinated biphenyls (PCB-105 and PCB-118) with larger and more aggressive tumors. Statistical models showed a negative association between pollutants' mixture and TC. BRAF V600E mutations were associated with PCB-153, PCB-138, and PCB-180., Conclusion: Our study suggests, for the first time in a case-control population, that exposure to some PFAS and PCBs associates with TC and some clinical and molecular features. On the contrary, an inverse correlation was found with both PFHxS and pollutants' mixture, likely due to a potential reverse causality.

Background: Per- and polyfluoroalkyl substances (PFAS) are widespread and environmentally persistent chemicals with immunotoxic properties. Children are prenatally exposed through maternal transfer of PFAS to cord blood, but no studies have investigated the relationship with childhood leukemia., Methods: We measured maternal serum levels of 19 PFAS in first-trimester samples collected in 1986-2010 and evaluated associations with acute lymphoblastic leukemia in full-term offspring (aged younger than 15 years) for 400 cases and 400 controls in the Finnish Maternity Cohort, matched on sample year, mother's age, gestational age, birth order, and child's sex. We analyzed continuous and categorical exposures, estimating odds ratios (ORs) and 95% confidence intervals (CIs) via conditional logistic regression adjusted for maternal smoking and correlated PFAS (ρ ≥ ±0.3). We also stratified by calendar period, mean diagnosis age, and the child's sex., Results: N-methyl-perfluorooctane sulfonamidoacetic acid was associated with acute lymphoblastic leukemia in continuous models (per each doubling in levels: ORperlog2 = 1.22, 95% CI = 1.07 to 1.39), with a positive exposure-response across categories (OR>90th percentile = 2.52, 95% CI = 1.33 to 4.78; Ptrend = .01). Although we found no relationship with perfluorooctane sulfonic acid overall, an association was observed in samples collected in 1986-1995, when levels were highest (median = 17.9 µg/L; ORperlog2 = 4.01, 95% CI = 1.62 to 9.93). A positive association with perfluorononanoic acid was suggested among first births (Pinteraction = .06). The N-methyl-perfluorooctane sulfonamidoacetic acid association was mainly limited to children diagnosed before age 5 years (Pinteraction = .02). We found no consistent patterns of association with other PFAS or differences by sex., Conclusions: These novel data offer evidence of a relationship between some PFAS and risk of the most common childhood cancer worldwide, including associations with the highest levels of perfluorooctanesulfonic acid and with a precursor, N-methyl-perfluorooctane sulfonamidoacetic acid., (Published by Oxford University Press 2023.)

Background: There is inconclusive evidence for an association between per- and polyfluoroalkyl substances (PFAS) and fetal growth., Objectives: We 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 Methods: We 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., Results: Among 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., Discussions: We 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Prenatal exposure to per- and polyfluoroalkyl substances (PFASs) influences neurodevelopment. Thyroid homeostasis disruption is thought to be a possible underlying mechanism. However, current epidemiological evidence remains inconclusive., Objectives: This study aimed to explore the effects of prenatal PFAS exposure on the intelligence quotient (IQ) of school-aged children and assess the potential mediating role of fetal thyroid function., Methods: The study included 327 7-year-old children from the Sheyang Mini Birth Cohort Study (SMBCS). Cord serum samples were analyzed for 12 PFAS concentrations and 5 thyroid hormone (TH) levels. IQ was assessed using the Wechsler Intelligence Scale for Children-Chinese Revised (WISC-CR). Generalized linear models (GLM) and Bayesian Kernel Machine Regression (BKMR) were used to evaluate the individual and combined effects of prenatal PFAS exposure on IQ. Additionally, the impact on fetal thyroid function was examined using a GLM, and a mediation analysis was conducted to explore the potential mediating roles of this function., Results: The molar sum concentration of perfluorinated carboxylic acids (ΣPFCA) in cord serum was significantly negatively associated with the performance IQ (PIQ) of 7-year-old children (β = -6.21, 95 % confidence interval [CI]: -12.21, -0.21), with more pronounced associations observed among girls (β = -9.57, 95 % CI: -18.33, -0.81) than in boys. Negative, albeit non-significant, cumulative effects were noted when considering PFAS mixture exposure. Prenatal exposure to perfluorooctanoic acid, perfluorononanoic acid, and perfluorooctanesulfonic acid was positively associated with the total thyroxine/triiodothyronine ratio. However, no evidence supported the mediating role of thyroid function in the link between PFAS exposure and IQ., Conclusions: Increased prenatal exposure to PFASs negatively affected the IQ of school-aged children, whereas fetal thyroid function did not serve as a mediator in this relationship., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Per- and polyfluoroalkyl substances (PFAS) have been shown to penetrate the blood-brain barrier (BBB) and accumulate in human brain. The BBB transmission and accumulation efficiency of PFAS, as well as the potential health risks from human co-exposure to legacy and emerging PFAS due to differences in transport efficiency, need to be further elucidated. In the present pilot study, 23 plasma samples from glioma patients were analyzed for 17 PFAS. The concentrations of PFAS in six paired brain tissue and plasma samples were used to calculate the BBB transmission efficiency of PFAS (R PFAS ). This R PFAS analysis was conducted with utmost care and consideration amid the limited availability of valuable paired samples. The results indicated that low molecular weight PFAS, including short-chain and emerging PFAS, may have a greater potential for accumulation in brain tissue than long-chain PFAS. As an alternative to perfluorooctane sulfonic acid (PFOS), 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) exhibited brain accumulation potential similar to that of PFOS, suggesting it may not be a suitable substitute concerning health risk in brain. The BBB transmission efficiencies of perfluorooctanoic acid, PFOS, and 6:2 Cl-PFESA showed similar trends with age, which may be an important factor influencing the entry of exogenous compounds into the brain. A favorable link between perfluorooctane sulfonamide (FOSA) and the development and/or progression of glioma may be implicated by a strong positive correlation (r 2  = 0.94; p < 0.01) between R FOSA and Ki-67 (a molecular marker of glioma). However, a causal relationship between R FOSA and glioma incidence were not established in the present study. The present pilot study conducted the first examination of BBB transmission efficiency of PFAS from plasma to brain tissue and highlighted the importance of reducing and/or controlling exposure to PFAS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Endocrine disruptors (EDs) have emerged as potential contributors to the development of type-2 diabetes. Perfluorooctane sulfonate (PFOS), is one of these EDs linked with chronic diseases and gathered attention due to its widespread in food., Objective: To assess at baseline and after 1-year of follow-up associations between estimated dietary intake (DI) of PFOS, and glucose homeostasis parameters and body-mass-index (BMI) in a senior population of 4600 non-diabetic participants from the PREDIMED-plus study., Methods: Multivariable linear regression models were conducted to assess associations between baseline PFOS-DI at lower bound (LB) and upper bound (UB) established by the EFSA, glucose homeostasis parameters and BMI., Results: Compared to those in the lowest tertile, participants in the highest tertile of baseline PFOS-DI in LB and UB showed higher levels of HbA1c [β-coefficient(CI)] [0.01 %(0.002 to 0.026), and [0.06 mg/dL(0.026 to 0.087), both p-trend ≤ 0.001], and fasting plasma glucose in the LB PFOS-DI [1.05 mg/dL(0.050 to 2.046),p-trend = 0.022]. Prospectively, a positive association between LB of PFOS-DI and BMI [0.06 kg/m 2 (0.014 to 0.106) per 1-SD increment of energy-adjusted PFOS-DI was shown. Participants in the top tertile showed an increase in HOMA-IR [0.06(0.016 to 0.097), p-trend = 0.005] compared to participants in the reference tertile after 1-year of follow-up., Discussion: This is the first study to explore the association between DI of PFOS and glucose homeostasis. In this study, a high baseline DI of PFOS was associated with a higher levels of fasting plasma glucose and HbA1c and with an increase in HOMA-IR and BMI after 1-year of follow-up., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Previous studies have identified the consumption of country foods (hunted/harvested foods from the land) as the primary exposure source of perfluoroalkyl acids (PFAA) in Arctic communities. However, identifying the specific foods associated with PFAA exposures is complicated due to correlation between country foods that are commonly consumed together., Methods: We used venous blood sample data and food frequency questionnaire data from the Qanuilirpitaa? ("How are we now?") 2017 (Q2017) survey of Inuit individuals ≥ 16 y of age residing in Nunavik ( n = 1,193 ). Adaptive elastic net, a machine learning technique, identified the most important food items for predicting PFAA biomarker levels while accounting for the correlation among the food items. We used generalized linear regression models to quantify the association between the most predictive food items and six plasma PFAA biomarker levels. The estimates were converted to percent changes in a specific PFAA biomarker level per standard deviation increase in the consumption of a food item. Models were also stratified by food type (market or country foods)., Results: Perfluorooctanesulfonic acid (PFOS), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) were associated with frequent consumption of beluga misirak (rendered fat) [14.6%; 95% confidence interval (CI): 10.3%, 18.9%; 14.6% (95% CI: 10.1%, 19.0%)], seal liver [9.3% (95% CI: 5.0%, 13.7%); 8.1% (95% CI: 3.5%, 12.6%)], and suuvalik (fish roe mixed with berries and fat) [6.0% (95% CI: 1.3%, 10.7%); 7.5% (95% CI: 2.7%, 12.3%)]. Beluga misirak was also associated with higher concentrations of perfluorohexanesulphonic acid (PFHxS) and perfluorononanoic acid (PFNA), albeit with lower percentage changes. PFHxS, perfluorooctanoic acid (PFOA), and PFNA followed some similar patterns, with higher levels associated with frequent consumption of ptarmigan [6.1% (95% CI: 3.2%, 9.0%); 5.1% (95% CI: 1.1%, 9.1%); 5.4% (95% CI: 1.8%, 9.0%)]. Among market foods, frequent consumption of processed meat and popcorn was consistently associated with lower PFAA exposure., Conclusions: Our study identifies specific food items contributing to environmental contaminant exposure in Indigenous or small communities relying on local subsistence foods using adaptive elastic net to prioritize responses from a complex food frequency questionnaire. In Nunavik, higher PFAA biomarker levels were primarily related to increased consumption of country foods, particularly beluga misirak , seal liver, suuvalik , and ptarmigan. Our results support policies regulating PFAA production and use to limit the contamination of Arctic species through long-range transport. https://doi.org/10.1289/EHP13556.

Background: Evidence suggests that exposure to per- and polyfluoroalkyl substances (PFAS) increases risk of high blood pressure (BP) during pregnancy. Prior studies did not examine associations with BP trajectory parameters (i.e., overall magnitude and velocity) during pregnancy, which is linked to adverse pregnancy outcomes., Objectives: To estimate associations of multiple plasma PFAS in early pregnancy with BP trajectory parameters across the second and third trimesters. To assess potential effect modification by maternal age and parity., Methods: In 1297 individuals, we quantified six PFAS in plasma collected during early pregnancy (median gestational age: 9.4 weeks). We abstracted from medical records systolic BP (SBP) and diastolic BP (DBP) measurements, recorded from 12 weeks gestation until delivery. BP trajectory parameters were estimated via Super Imposition by Translation and Rotation modeling. Subsequently, Bayesian Kernel Machine Regression (BKMR) was employed to estimate individual and joint associations of PFAS concentrations with trajectory parameters - adjusting for maternal age, race/ethnicity, pre-pregnancy body mass index, income, parity, smoking status, and seafood intake. We evaluated effect modification by age at enrollment and parity., Results: We collected a median of 13 BP measurements per participant. In BKMR, higher concentration of perfluorooctane sulfonate (PFOS) was independently associated with higher magnitude of overall SBP and DBP trajectories (i.e., upward shift of trajectories) and faster SBP trajectory velocity, holding all other PFAS at their medians. In stratified BKMR analyses, participants with ≥ 1 live birth had more pronounced positive associations between PFOS and SBP velocity, DBP magnitude, and DBP velocity - compared to nulliparous participants. We did not observe significant associations between concentrations of the overall PFAS mixture and either magnitude or velocity of the BP trajectories., Conclusion: Early pregnancy plasma PFOS concentrations were associated with altered BP trajectory in pregnancy, which may impact future cardiovascular health of the mother., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In utero and children's exposure to per- and polyfluoroalkyl substances (PFAS) is a major concern in health risk assessment as early life exposures are suspected to induce adverse health effects. Our work aims to estimate children's exposure (from birth to 12 years old) to PFOA and PFOS, using a Physiologically-Based Pharmacokinetic (PBPK) modelling approach. A model for PFAS was updated to simulate the internal PFAS exposures during the in utero life and childhood, and including individual characteristics and exposure scenarios (e.g., duration of breastfeeding, weight at birth, etc.). Our approach was applied to the HELIX cohort, involving 1,239 mother-child pairs with measured PFOA and PFOS plasma concentrations at two sampling times: maternal and child plasma concentrations (6 to 12 y.o). Our model predicted an increase in plasma concentrations during fetal development and childhood until 2 y.o when the maximum concentrations were reached. Higher plasma concentrations of PFOA than PFOS were predicted until 2 y.o, and then PFOS concentrations gradually became higher than PFOA concentrations. From 2 to 8 y.o, mean concentrations decreased from 3.1 to 1.88 µg/L or ng/mL (PFOA) and from 4.77 to 3.56 µg/L (PFOS). The concentration-time profiles vary with the age and were mostly influenced by in utero exposure (on the first 4 months after birth), breastfeeding (from 5 months to 2 (PFOA) or 5 (PFOS) y.o of the children), and food intake (after 3 (PFOA) or 6 (PFOS) y.o of the children). Similar measured biomarker levels can correspond to large differences in the simulated internal exposures, highlighting the importance to investigate the children's exposure over the early life to improve exposure classification. Our approach demonstrates the possibility to simulate individual internal exposures using PBPK models when measured biomarkers are scarce, helping risk assessors in gaining insight into internal exposure during critical windows, such as early life., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Per- and polyfluoroalkyl substances (PFAS) are a wide-ranging group of chemicals that have been used in a variety of polymer and surfactant applications. While 3M Cordova, Illinois was not one of 3M's primary manufacturing facilities for the legacy long-chain PFAS (PFOS, PFOA, PFHxS), it has been a major manufacturing site for short-chain PFAS (compounds that are or may degrade to PFBS or PFBA). The purpose of this research focused on: 1) an analysis of biomonitoring data of employees and retirees, and 2) an analysis of the cohort mortality of workers from 1970 to 2018. Employees had higher PFBS and PFBA serum concentrations than the retirees, while retirees had higher concentrations for PFOS, PFOA, and PFHxS. Compared to the 2017-2018 NHANES data, employees' PFOS and PFHxS concentrations in 2022 were two-fold higher, with PFOA levels comparable. These NHANES data did not include serum PFBS or PFBA. Cross-sectional trends of PFOS and PFOA levels from 1997 to 2022 showed PFOS declined from 151 ng/mL to 10.4 ng/mL. Similarly, PFOA decreased from 100 ng/mL to 1.5 ng/mL. A longitudinal analysis of 48 participants with measurements in both 2006 and 2022 showed concentrations decreased by 74% for PFOS and 90% for PFOA. In the mortality study, 1707 employees who worked 1 day or longer were followed for an average of 25.6 years and had 143 (8%) deaths. There were no significantly elevated risks for any specific cause of death, regardless of latency period (0 or 15 years). While no specific PFAS exposures were examined, worker mortality experience (1970-2018) was analyzed by major departments representing primary work areas. Employees and retirees at the Cordova facility continue to have elevated PFOS and PFHxS serum concentrations compared to the general population, however, their legacy PFAS concentrations have declined over time, consistent with the estimated serum elimination half-lives of these PFAS in humans assuming nominal ambient exposures. For PFBS and PFBA, the results indicated no long-term accumulation in the blood likely due to their short serum elimination half-lives. After nearly 50 years of follow-up, this Cordova workforce showed no increased risk of mortality from cancer or any other specific cause of death., Competing Interests: Declaration of competing interest All authors are current employees of 3M Company. 3M, the company that sponsored this research, is a former manufacturer of PFOS, PFHxS and PFOA related materials and a current manufacturer of PFBS and PFBA related products., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

This study aimed to explore the isomer-specific, sex-specific, and joint associations of PFAS and red blood cell indices. We used data of 1,238 adults from the Isomers of C8 Health Project in China. Associations of PFAS isomers and red blood cell indices were explored using multiple linear regression models, Bayesian Kernel Machine Regression models and subgroup analysis across sex. We found that serum concentration of linear (n-) and branched (Br-) isomers of perfluorooctane sulfonate (PFOS) and perfluorohexanesulfonic acid (PFHxS) were significantly associated with red blood cell indices in single-pollutant models, with stronger associations observed for n-PFHxS than Br-PFHxS, in women than in men. For instance, the estimated percentage change in hemoglobin concentration for n-PFHxS (3.65%; 95% CI: 2.95%, 4.34%) was larger than that for Br-PFHxS (0.96%; 95% CI: 0.52%, 1.40%). The estimated percentage change in red blood cell count for n-PFHxS in women (2.55%; 95% CI: 1.81%, 3.28%) was significantly higher than that in men (0.12%; 95% CI: -1.04%, 1.29%) ( P inter < 0.001). Similarly, sex-specific positive association of PFAS mixture and outcomes was observed. Therefore, the structure, susceptive population, and joint effect of PFAS isomers should be taken into consideration when evaluating the health risk of chemicals.

Background: Per- and polyfluoroalkyl substances (PFAS) are global contaminants. Seafood consumption is a possible PFAS exposure route to humans while the isomer specific analysis has not been conducted., Methods: Perfluorooctane sulfonate (PFOS), perfluoroheptane sulfonate (PFHpS) and perfluorohexane sulfonate (PFHxS) were investigated in residents of Kyoto, Japan (n = 51). The relationship between plasma PFAS and seafood consumption biomarker, the ratio of eicosapentaenoic acid to arachidonic acid (EPA/AA) was examined by multiple regression analysis., Results: Linear PFOS concentrations showed a significant positive correlation with the EPA/AA ratio in plasma samples (β = 6.80, p = 0.0014). Linear PFHpS was marginally associated with EPA/AA ratio (β = 0.178, p = 0.0874). Branched PFOS isomers and PFHxS had no associations with EPA/AA ratios., Conclusion: Seafood intake may be a significant exposure pathway for PFAS, such as PFOS but the isomers differ.

Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) are synthetic chemicals that have been used in various industries and household products. These can easily accumulate in the human body, causing adverse effects on human health. In this study, a high-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous analysis of PFOA and linear PFOS in human serum. Owing to a lack of PFOA- and PFOS-free human serum, 13 C 8 -PFOA and 13 C 8 -PFOS were used as surrogate analytes for quantification. A sensitive and selective sample preparation method was developed and optimized by combining solid-phase extraction and protein precipitation method. The lower limit of quantification was 0.05 ng/mL, and the analytical response was linear up to 10 ng/mL for both PFOA and linear PFOS. Chromatographic separation of the linear PFOS from branched isomers was achieved within 5.5 min. The method was validated at various concentrations and afforded acceptable accuracy and precision values. After validation, the method was successfully applied to evaluate the exposure levels of PFOA and linear PFOS in the Korean population. The serum concentrations of PFOA and linear PFOS were 0.42-28.3 ng/mL and 0.81-57.6 ng/mL, respectively. The median concentration of linear PFOS was approximately 2.6-fold higher than that of PFOA. The concentration of PFOA was higher in women than men (p < 0.05) and that of linear PFOS was not significantly different between men and women. Therefore, a sensitive, selective, and reliable bioanalytical method was developed and validated. This method can potentially be applied to biomonitoring studies involving PFOA and linear PFOS., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Cattle that were at steady-state serum polyfluoroalkyl substances (PFAS) concentrations due to several years of exposure to water contaminated by residues of Aqueous Film-Forming (AFFF) firefighting foam had perfluorooctane sulphonate (PFOS) isomers, perfluoroheptane sulphonate (PFHpS), perfluorohexane sulphonate (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) in serum. Elimination serum half-lives were determined in five heifers from serial blood sampling over 215 days. Eleven additional animals that had blood sampled on day 19 (d19) were euthanised on d63. PFAS half-life estimates from the serial blood sampling and from d19/d63 data were not significantly different. The combined (n = 16) serum half-lives (in days) were: total PFOS (tPFOS, 74.1 ± 13.4), PFHpS (45.7 ± 9.4), PFHxS (9.3 ± 1.3), PFNA (12.3 ± 3.2) and PFDA (60.4 ± 10.4). The half-lives of linear PFOS (L-PFOS, 69.4 ± 11.6) and mono branched PFOS isomers (m-PFOS, 83.6 ± 19) were not significantly different from tPFOS, but for the di-branched isomers (di-PFOS), the serum half-life was significantly lower (29.9 ± 5.8). Animal age (1.4-12.3 years old) and serum concentration at the start of depuration did not influence half-lives, and there was no difference between steers and heifers. Consideration of serum and tissue PFAS concentrations at d63 and d215 indicated there was no difference in tPFOS depuration from serum or muscle, but elimination from liver and kidney may be slightly longer. Depuration of PFHpS is essentially the same in serum, kidney and liver, and it is expected depletion from muscle would be comparable. The short half-life of di-PFOS, PFHxS and PFNA did not allow an assessment of clearance from tissues because they were not measurable at d215 but based on the results for PFOS and PFHpS, elimination of PFHxS from tissues is expected to mirror that from serum. Human health risk assessment implications are discussed.

We assessed how the interaction between mono-(2-ethylhexyl) phthalate (MEHP) in maternal sera and the maternal genotypes associated with nuclear receptors affect fatty acid levels in a prospective birth cohort study of pregnant Japanese individuals (n = 437) recruited in Sapporo between 2002 and 2005. We analyzed MEHP and fatty acids using gas chromatography-mass spectrometry. Thirteen single nucleotide polymorphisms of peroxisome proliferator-activated receptor (PPAR) alpha, PPAR gamma (PPARG), PPARG coactivator 1A (PPARGC1A), PPAR delta, constitutive androstane receptor, liver X receptor (LXR) alpha, and LXR beta (LXRB) were analyzed using real-time PCR. Multiple linear regression models were used to confirm the influence of log 10 -transformed MEHP levels and maternal genotypes on log 10 -transformed fatty acid levels. When the effects of the interaction between MEHP levels and the maternal PPARGC1A (rs8192678) genotype on oleic acid levels were evaluated, the estimated changes (95 % confidence intervals) in oleic acid levels against MEHP levels, maternal PPARGC1A (rs8192678)-GA/AA genotype, and the interaction between them showed a mean reduction of 0.200 (0.079, 0.322), mean reduction of 0.141 (0.000, 0.283), and mean increase of 0.145 (0.010, 0.281), respectively, after adjusting for the perfluorooctanesulfonate level. The effects of the interaction between MEHP levels and maternal LXRB (rs2303044) genotype on linoleic acid levels was also significant (p int  = 0.010). In conclusion, the interaction between MEHP and the maternal genotypes PPARGC1A (rs8192678) and LXRB (rs2303044) decreased fatty acid levels. Further, the interaction between MEHP and PPARGC1A (rs8192678) may have a greater effect on fatty acid levels than the interaction between PFOS and PPARGC1A., (Copyright © 2021 Elsevier Inc. All rights reserved.)

We assessed the associations between perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) levels in third trimester maternal serum, the maternal genotypes of genes encoding nuclear receptors, and birth outcomes. We studied a prospective birth cohort of healthy pregnant Japanese women (n = 372) recruited in Sapporo between July 2002 and October 2005. We analyzed PFOS and PFOA levels using liquid chromatography-tandem mass spectrometry and analyzed 13 single nucleotide polymorphisms (SNPs) of proliferator-activated receptor alpha, gamma, gamma coactivator 1A, delta, constitutive androstane receptor, liver X receptor alpha, and beta (LXRB) using real-time polymerase reaction (PCR). We employed multiple linear regression models to establish the influences of log 10 -transformed PFOS and PFOA levels and maternal genotypes on birth size. In female infants, we identified interactions between PFOS levels, the maternal genotype of LXRB (rs1405655), and birth weight. The estimated mean changes in birth weight in response to PFOS levels, the maternal genotype LXRB (rs1405655)-TC/CC (compared to TT), and their interactions were -502.9 g (95 % confidence interval [CI] = -247.3, -758.5 g), -526.3 g (95 % CI = -200.7, -852.0 g), and 662.1 g (95 % CI = 221.0, 1,103.2 g; p int = 0.003), respectively. Interactions between PFOS levels and the maternal genotype of LXRB (rs1405655) also significantly affected birth chest circumference and the Ponderal index (p int = 0.037 and 0.005, respectively). Thus, interactions between PFOS levels and the maternal genotype of LXRB (rs1405655) affects birth sizes in female infants. We found that certain SNPs modify the effects of PFOS levels on birth size., (Copyright © 2021. Published by Elsevier Inc.)

Context: Per- and polyfluoroalkyl substances (PFAS) are widespread chemicals that may affect sex hormones and accelerate reproductive aging in midlife women., Objective: To examine associations between serum PFAS concentrations at baseline (1999-2000) and longitudinal serum concentrations of follicle-stimulating hormone (FSH), estradiol, testosterone, and sex hormone-binding globulin (SHBG) at baseline and through 2015-2016., Design: Prospective cohort., Setting: General community., Participants: 1371 midlife women 45 to 56 years of age at baseline in the Study of Women's Health Across the Nation (SWAN)., Main Outcome Measure(s): FSH, estradiol, testosterone, SHBG., Results: In linear mixed models fitted with log-transformed hormones and log-transformed PFAS adjusting for age, site, race/ethnicity, smoking status, menopausal status, parity, and body mass index, FSH was positively associated with linear perfluorooctanoate [n-PFOA; 3.12% (95% CI 0.37%, 5.95%) increase for a doubling in serum concentration), linear perfluorooctane sulfonate [PFOS; 2.88% (0.21%, 5.63%)], branched perfluorooctane sulfonate [2.25% (0.02%, 4.54%)], total PFOS (3.03% (0.37%, 5.76%)), and 2-(N-ethyl-perfluorooctane sulfonamido) acetate [EtFOSAA; 1.70% (0.01%, 3.42%)]. Estradiol was inversely associated with perfluorononanoate [PFNA; -2.47% (-4.82%, -0.05%)) and n-PFOA (-2.43% (-4.97%, 0.18%)]. Significant linear trends were observed in the associations between PFOS and EtFOSAA with SHBG across parity (Ps trend ≤ 0.01), with generally inverse associations among nulliparous women but positive associations among women with 3+ births. No significant associations were observed between PFAS and testosterone., Conclusions: This study observed positive associations of PFOA and PFOS with FSH and inverse associations of PFNA and PFOA with estradiol in midlife women during the menopausal transition, consistent with findings that PFAS affect reproductive aging., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Prenatal exposure to perfluoroalkyl substances (PFAS) has been reported to affect body weight from birth to childhood, but the results remain inconclusive. We investigated whether umbilical cord blood concentrations of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are associated with children's risk trajectory for obesity. 600 children were randomly selected from the Hamamatsu Birth Cohort for Mothers and Children (HBC study) and their umbilical cord serum PFAS concentrations were quantified. Participants underwent BMI measurements at ages 1, 4, 10, 18, 24, 32, 40, 50, and 66 months. Growth curve modeling with random intercept was performed with standardized BMI as outcome variable. PFOS was negatively associated with standardized BMI (β =  - 0.34; p = 0.01), with a marginally significant interaction with the child's age (β = 0.0038; p = 0.08). PFOA was negatively associated with standardized BMI (β =  - 0.26, 95% CI - 0.51, 0; p = 0.05), with a significant interaction with the child's age (β = 0.005; p = 0.01). Stratified analysis by sex revealed that these effects were significant only among girls. Prenatal exposure to PFAS initially was associated with lower standardized BMI during infancy, but this effect dissipated over time and reversed in direction during later childhood. The effects of prenatal PFAS on higher standardized BMI is stronger in girls., (© 2021. The Author(s).)

Prenatal sex hormones affect fetal growth; for example, prenatal exposure to low levels of androgen accelerates female puberty onset. We assessed the association of perfluoroalkyl substances (PFASs) in maternal sera and infant genotypes of genes encoding enzymes involved in sex steroid hormone biosynthesis on cord sera sex hormone levels in a prospective birth cohort study of healthy pregnant Japanese women (n = 224) recruited in Sapporo between July 2002 and October 2005. We analyzed PFAS and five sex hormone levels using liquid chromatography-tandem mass spectrometry. Cytochrome P450 (CYP) 17A1 (CYP17A1 rs743572), 19A1 (CYP19A1 rs10046, rs700519, and rs727479), 3β-hydroxysteroid dehydrogenase type 1 (HSD3B1 rs6203), type 2 (HSD3B2 rs1819698, rs2854964, and rs4659175), 17β-hydroxysteroid dehydrogenase type 1 (HSD17B1 rs605059, rs676387, and rs2676531), and type 3 (HSD17B3 rs4743709) were analyzed using real-time PCR. Multiple linear regression models were used to establish the influence of log 10 -transformed PFAS levels and infant genotypes on log 10 -transformed sex steroid hormone levels. When the interaction between perfluorooctanesulfonate (PFOS) levels and female infant genotype CYP17A1 (rs743572) on the androstenedione (A-dione) levels was considered, the estimated changes (95 % confidence intervals) in A-dione levels against PFOS levels, female infant genotype CYP17A1 (rs743572)-AG/GG, and interaction between them showed a mean increase of 0.445 (0.102, 0.787), mean increase of 0.392 (0.084, 0.707), and mean reduction of 0.579 (0.161, 0.997) (P int  = 0.007), respectively. Moreover, a female-specific interaction with testosterone levels was observed. A-dione and T levels showed positive main effects and negative interaction with PFOS levels and the female infant CYP17A1 genotype., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Context: Per- and polyfluoroalkyl substances (PFAS) may alter body composition by lowering anabolic hormones and increasing inflammation, but data are limited, particularly in adolescence when body composition is rapidly changing., Objective: To evaluate associations of PFAS plasma concentrations in childhood with change in body composition through early adolescence., Methods: A total of 537 children in the Boston-area Project Viva cohort participated in this study. We used multivariable linear regression and Bayesian kernel machine regression (BKMR) to examine associations of plasma concentrations of 6 PFAS, quantified by mass spectrometry, in mid-childhood (mean age, 7.9 years; 2007-2010) with change in body composition measured by dual-energy x-ray absorptiometry from mid-childhood to early adolescence (mean age, 13.1 years)., Results: In single-PFAS linear regression models, children with higher concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorodecanoate (PFDA), and perfluorohexane sulfonate (PFHxS) had less accrual of lean mass (eg, -0.33 [95% CI: -0.52, -0.13] kg/m2 per doubling of PFOA). Children with higher PFOS and PFHxS had less accrual of total and truncal fat mass (eg, -0.32 [95% CI: -0.54, -0.11] kg/m2 total fat mass per doubling of PFOS), particularly subcutaneous fat mass (eg, -17.26 [95% CI -32.25, -2.27] g/m2 per doubling of PFOS). Children with higher PFDA and perfluorononanoate (PFNA) had greater accrual of visceral fat mass (eg, 0.44 [95% CI: 0.13, 0.75] g/m2 per doubling of PFDA). Results from BKMR mixture models were consistent with linear regression analyses., Conclusion: Early life exposure to some but not all PFAS may be associated with adverse changes in body composition., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To investigate the prospective associations of life-course perfluoroalkyl substances (PFASs) exposure with glucose homeostasis at adulthood., Methods: We calculated insulin sensitivity and beta-cell function indices based on 2-h oral glucose tolerance tests at age 28 in 699 Faroese born in 1986-1987. Five major PFASs were measured in cord whole blood and in serum from ages 7, 14, 22, and 28 years. We evaluated the associations with glucose homeostasis measures by PFAS exposures at different ages using multiple informant models fitting generalized estimating equations and by life-course PFAS exposures using structural equation models., Results: Associations were stronger for perfluorooctane sulfonate (PFOS) and suggested decreased insulin sensitivity and increased beta-cell function-for example, β (95% CI) for log-insulinogenic index per PFOS doubling = 0.12 (0.02, 0.22) for prenatal exposures, 0.04 (-0.10, 0.19) at age 7, 0.07 (-0.07, 0.21) at age 14, 0.05 (-0.04, 0.15) at age 22, and 0.04 (-0.03, 0.11) at age 28. Associations were consistent across ages (P for age interaction > 0.10 for all PFASs) and sex (P for sex interaction > 0.10 for all PFASs, except perfluorodecanoic acid). The overall life-course PFOS exposure was also associated with altered glucose homeostasis (P = 0.04). Associations for other life-course PFAS exposures were nonsignificant., Conclusions: Life-course PFAS exposure is associated with decreased insulin sensitivity and increased pancreatic beta-cell function in young adults., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)