Polyfluoroalkyl Substances Mixtures Research Articles

Ecotoxicity of single and mixture of perfluoroalkyl substances (PFOS and PFOA) in soils to the earthworm Aporrectodea caliginosa

Per and polyfluoroalkyl substances (PFAS) are persistent compounds that are massively used in industry, consumer goods and fire-fighting foams. Soil contamination by PFAS is a major environmental concern, and there is a lack of knowledge on both their ecotoxicological mechanisms and the concentrations that induce adverse effects especially to non-target organisms, particularly in the case of PFAS mixtures. This study contributes to filling these gaps by assessing and modelling the effects of PFAS (in single and in mixtures for PFOS and PFOA at different environmental doses) on juvenile endogeic earthworms of a common species in European soils (Aporrectodea caliginosa) at different levels of biological organization (sub-individual and individual). The results showed for the first time combined strong ecotoxicological effects of PFAS on earthworm survival, integumental integrity, growth, sexual maturity and on genomic stability notably with the induction of DNA breaks associated with no abnormal oxidative DNA-lesion levels. Our results demonstrated significant effects at 0.3 mg kg−1 and additive effects in case of mixtures.

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

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

Ecotoxicity and Accumulation of Perfluorononanoic Acid in the Fathead Minnow (Pimephales promelas) and an Approach to Developing Protective Thresholds in the Aquatic Environment Through Species Sensitivity Distribution.

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous in the environment. Locations where PFAS-containing aqueous film-forming foam (AFFF) has been used or accidentally released have resulted in persistently high concentrations of PFAS, including in surface water that may be adjacent to release sites. Perfluorooctane sulfonic acid (PFOS) is most frequently measured near AFFF release sites; however, other PFAS are being quantified more frequently and, of those, perfluorononanoic acid (PFNA) is common. The goal of our study was to fill data gaps on PFNA toxicity to freshwater fish using the fathead minnow (Pimephales promelas). We aimed to understand how PFNA may impact apical endpoints following a 42-day exposure to mature fish and a 21-day exposure to second-generation larval fish. Exposure concentrations were 0, 124, 250, 500, and 1000 µg/L for both adult (F0) and larval (F1) generations. The most sensitive endpoint measured was development in the F1 generation at concentrations of ≥250 µg/L. The 10% and 20% effective concentration of the tested population for the F1 biomass endpoint was 100.3 and 129.5 µg/L, respectively. These data were collated with toxicity values from the primary literature on aquatic organisms exposed to PFNA for subchronic or chronic durations. A species sensitivity distribution was developed to estimate a screening-level threshold for PFNA. The resulting hazard concentration protective of 95% of the freshwater aquatic species was 55 µg PFNA/L. Although this value is likely protective of aquatic organisms exposed to PFNA, it is prudent to consider that organisms experience multiple stressors (including many PFAS) simultaneously; an approach to understand screening-level thresholds for PFAS mixtures remains an uncertainty within the field of ecological risk assessment. Environ Toxicol Chem 2023;42:2229-2236. © 2023 SETAC.

Computational Modeling of Human Serum Albumin Binding of Per- and Polyfluoroalkyl Substances Employing QSAR, Read-Across, and Docking.

Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals in widespread use that have been shown to be toxic to wildlife and humans. Human serum albumin (HSA) is a known transport protein that binds PFAS at various sites, leading to bioaccumulation and long-term toxicity. In silico tools like quantitative structure-activity relationship (QSAR), read-across, and quantitative read-across structure-property relationship (q-RASPR) are proven techniques for modeling chemical toxicity based on experimental data which can be used to predict the toxicity of untested and new chemicals, while at the same time, help to identify the major features responsible for toxicity. Classification-based and regression-based QSAR models are employed in the present study to predict the binding affinities of 24 PFAS to HSA. Regression-based QSAR models revealed that the packing density index (PDI) and quantitative estimation of drug-likeness (QED) descriptors were both positively correlated with higher binding affinity, while the classification-based QSAR model showed the average connectivity index of order 4 (X4A) descriptor was inversely correlated with binding affinity. Whereas molecular docking studies suggested that PFAS with the highest binding affinity to HSA create hydrogen bonds with Arg348 and salt bridges with Arg348 and Arg485, PFAS with lower binding affinity either showed no interactions with either amino acid or only interactions with Arg348. Among the studied PFAS, perfluoroalkyl acids (PFAA) with large carbon chain length (>C10) have one of the lowest binding affinities, compared to PFAA with carbon chain length ranging from 7 to 9, which showed the highest affinity to HSA. Generalized Read-Across (GenRA) was used to predict toxicity outcomes for the top five highest binding affinity PFAS based on 10 structural analogs for each and found that all are predicted as being chronic to sub-chronically toxic to HSA. The developed in silico models presented in this work can provide a framework for designing PFAS alternatives, screening compounds currently in use, and for the study of PFAS mixture toxicity, which is an area of intense research.

Per- and polyfluoroalkyl substances and the associated thyroid cancer risk: A case-control study in China

The role of perfluoroalkyl and polyfluoroalkyl substances (PFAS) as thyroid carcinogens is unclear. Therefore, we intended to identify associations between each PFAS congener and their mixture with thyroid cancer risk. This case-control study of thyroid cancer was conducted in Shijiazhuang, Hebei Province, China. Three hundred participants were recruited from January to May 2022 and were matched according to sex and age. Twelve PFAS were assessed using ultra-high-performance liquid chromatography-tandem mass spectrometry. Associations between PFAS congeners and thyroid cancer risk were considered under conditional logistic regression analysis and a restricted cubic spline model. Mixture effects were also assessed with quantile g-computation and a Bayesian kernel machine regression model. Compared to the first tertile, third tertile PFOA, PFNA, PFHxS, PFDA, and PFUnDA concentrations were associated with lower thyroid cancer risk (ORPFOA: 0.32, 95% confidence interval (CI): 0.15–0.69; ORPFNA: 0.18, 95% CI: 0.07–0.46; ORPFHxS: 0.37, 95% CI: 0.15–0.92; ORPFDA: 0.07, 95% CI: 0.02–0.23; ORPFUnDA: 0.12, 95% CI: 0.05–0.30) after adjusting for confounding factors. PFNA, PFDA, and PFUnDA had a negative dose-response relationship with thyroid cancer risk. Mixture analysis also showed that thyroid cancer risk is negatively associated with the overall mixture and carboxylates. In the overall mixture, PFOS and PFDA contributed most to positive and negative changes in thyroid cancer risk, respectively. However, PFOS, PFNA, PFDA, and PFUnDA were of equally high importance. This study is the first to confirm the effects of the PFAS mixture on thyroid cancer, and further large-scale prospective studies are still warranted to test these inverse associations.

Prenatal exposure to per- and polyfluoroalkyl substances and infant sleep disturbance: A prospective cohort study

BackgroundPrenatal exposure to per- and polyfluoroalkyl substances (PFAS) may adversely affect fetal brain development, yet no study has investigated the potential association between prenatal PFAS exposure and infant sleep. ObjectivesTo explore the associations of prenatal PFAS exposure with infant sleep disturbances during the first year of life in a prospective cohort study. MethodsWe recruited 4127 pregnant women from the Shanghai Birth Cohort (SBC) and followed their children from birth to 12 months old. A total of 2366 infants were included in the 6-month analyses, and 2466 infants in the 12-month analyses. Ten PFAS were quantified in blood serum collected in the first trimester. Sleep quality was measured using the Brief Infant Sleep Questionnaire. We used multiple linear regression and multinomial logistic regression to estimate the individual effects of PFAS on sleep outcomes. We utilized a quantile-based g-computation model to determine the joint effects of the PFAS mixture on infant sleep outcomes. Additionally, generalized estimating equation (GEE) models were performed to examine the longitudinal effects of PFAS exposure during pregnancy. ResultsIn infants aged 6 months, perfluorooctane sulfonate and perfluoroheptanoic acid were associated with a more than 2-fold risk of parent-reported sleep problems as severe. Perfluorodecanoic acid was associated with an increased risk of often or almost always snoring in one-year-old infants (relative risk ratios, 1.79; 95% CI, 1.12–2.86). PFAS mixtures were positively associated with nighttime awakenings both among infants aged 6 months (β, 0.11; 95% CI, 0.04–0.19) and 12 months (β, 0.11; 95% CI, 0.05–0.18). Prenatal exposure to PFAS were associated with longer sleep latency, increased nighttime awakenings, longer nocturnal wakefulness hours, snoring, and earlier sleep-onset time in infants aged 6–12 months, according to GEE models. ConclusionsOur study suggests that prenatal exposure to PFAS may increase the risk of sleep disturbance in infants.

1419-P: Pandemic-Specific Associations of Maternal Exposure to Per- and Polyfluoroalkyl Substances and Glucose Metabolisms—A Cross-Sectional Analysis in Birth Cohort in Hong Kong

Introduction: Per- and polyfluoroalkyl substances (PFAS) have adverse cardiometabolic effects. Methods: We conducted a cross-sectional analysis in 1601 mothers who had joined the Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) study in Hong Kong in 2001-2006. All mothers underwent a 75g-oral-glucose-tolerance test at 24-32 weeks of gestation. We measured serum concentrations of six PFAS biomarkers using high-performance LC-MS-MS. We fitted linear-regression, weighted-quantile-sum (WQS) regression, and quantile-g-computation (qgcomp) models to estimate the associations of individual PFAS and their mixture with levels of HbA1c and plasma-glucose (PG). Subgroup analyses were performed based on the enrollment period by the severe-acute-respiratory-syndrome (SARS) epidemic in Hong Kong between March 2003 and May 2004. Results: Maternal exposure to PFAS mixture was associated with increased HbA1c in both WQS (β=0.05, 95% CI: 0.02-0.07) and qgcomp models (β=0.04, 95% CI: 0.01-0.06). We did not observe significant associations of PFAS mixture with fasting PG, 1-h and 2-h PG in both models, except for 2-h PG in qgcmop model (β=0.074, 95% CI: 0.01-0.15). Pandemic-specific analyses showed a significant association of PFAS mixture with increased HbA1c in peri-SARS but not in pre-SARS and post-SARS epidemic period. Perfluorooctanoic-acid (PFOA) and perfluorooctane-sulfonic-acid (PFOS) were the main contributors to the overall positive effects on HbA1c. The level of PFOS was highest during the peri-SARS epidemic (median [IQR]: 24.7 [42.6-89.5] ng/mL) compared with pre-SARS (12.6 [20.0-49.8] ng/mL) and post-SARS (20.6 [27.8-46.4] ng/mL) epidemic. Conclusions: Maternal exposure to PFAS mixture is associated with glucose metabolisms during pregnancy. Pandemic-specific associations call for further studies on its adverse health effects during the COVID-19 pandemic. Disclosure A.Yang: None. C.H.Tam: None. R.Ozaki: None. W.L.Lowe: None. B.E.Metzger: None. W.H.Tam: None. C.K.Wong: None. R.C.Ma: Advisory Panel; AstraZeneca, Merck & Co., Inc., Other Relationship; Bayer Inc., Boehringer-Ingelheim, Research Support; Tricida, Inc., Roche Diagnostics, Novo Nordisk. Funding Health and Medical Research Fund (13140761); Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institute of Diabetes and Digestive and Kidney Diseases (R01HD34242, R01HD34243); Research Grants Council of Hong Kong (473408, 471713)

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

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

Mixtures of per- and poly-fluoroalkyl substances (PFAS) reduce the in vitro activation of human T cells and basophils

In the last decades, per- and poly-fluoroalkyl substances (PFAS), widely used industrial chemicals, have been in the center of attention because of their omnipotent presence in water and soils worldwide. Although efforts have been made to substitute long-chain PFAS towards safer alternatives, their persistence in humans still leads to exposure to these compounds. PFAS immunotoxicity is poorly understood as no comprehensive analyses on certain immune cell subtypes exist. Furthermore, mainly single entities and not PFAS mixtures have been assessed. In the present study we aimed to investigate the effect of PFAS (short-chain, long-chain and a mixture of both) on the in vitro activation of primary human immune cells.Our results show the ability of PFAS to reduce T cells activation. In particular, exposure to PFAS affected T helper cells, cytotoxic T cells, Natural Killer T cells, and Mucosal associated invariant T (MAIT) cells, as assessed by multi-parameter flow cytometry. Furthermore, the exposure to PFAS reduced the expression of several genes involved in MAIT cells activation, including chemokine receptors, and typical proteins of MAIT cells, such as GZMB, IFNG and TNFSF15 and transcription factors. These changes were mainly induced by the mixture of both short- and long-chain PFAS. In addition, PFAS were able to reduce basophil activation induced by anti-FcεR1α, as assessed by the decreased expression of CD63.Our data clearly show that the exposure of immune cells to a mixture of PFAS at concentrations mimicking real-life human exposure resulted in reduced cell activation and functional changes of primary innate and adaptive human immune cells.

Association between Serum Per- and Polyfluoroalkyl Substance Levels and Risk of Central and Peripheral Precocious Puberty in Girls.

Concerns about the endocrine-disrupting effects of per- and polyfluoroalkyl substances (PFASs) have raised questions about their potential influence on precocious puberty in girls, which is an emerging concern in some populations. However, epidemiological evidence is lacking. In this study, 882 serum samples were collected from girls with central precocious puberty (CPP, n = 226), peripheral precocious puberty (PPP, n = 316), and healthy controls (n = 340) in 2021 in Shanghai, China. The serum levels of 25 legacy and emerging PFASs and 17 steroids were measured. Results showed that PFAS exposure was positively associated with estradiol levels. Eleven PFASs were significantly or marginally associated with the higher odds of the overall precocious puberty. Across subtypes, PFASs were more clearly associated with PPP, while the associations with CPP were consistent in direction but did not reach statistical significance. These findings were consistent with the assessment of PFAS mixtures using quantile-based g-computation (qgcomp) and Bayesian kernel machine regression, with perfluorobutane sulfonate and 6:2 polyfluorinated ether sulfonate showing the highest contribution to joint effects. Although changes in serum estradiol could arise from various factors, our results suggest that the PFAS exposure may contribute to the increase in estradiol secretion, thereby increasing the risk of precocious puberty, especially PPP. The potential effects of PFASs on precocious puberty warrant further investigation, given the associated complications of public health concern, including psychological distress and increased risk of multiple diseases.

Plasma concentrations of per- and polyfluoroalkyl substances in pregnancy and breastfeeding duration in Project Viva

BackgroundPer- and polyfluoroalkyl substances (PFAS) may disrupt mammary gland development and function; thereby inhibiting milk supply and breastfeeding duration. However, conclusions on the potential effects of PFAS and breastfeeding duration are limited by prior epidemiologic studies that inconsistently adjusted for past cumulative breastfeeding duration and by a lack of examination of the joint effects of PFAS mixtures. MethodsIn Project Viva, a longitudinal cohort that enrolled pregnant participants from 1999 to 2002 in the greater Boston, MA area, we studied 1079 women who ever attempted to lactate. We investigated associations of plasma concentrations of select PFAS in early pregnancy (mean: 10.1 weeks gestation) with breastfeeding termination by 9 months, after which women typically cite self-weaning as the reason for terminating breastfeeding. We used Cox regression for single-PFAS models and quantile g-computation for mixture models, adjusting for sociodemographics, prior breastfeeding duration, and weeks of gestation at the time of blood draw. ResultsWe detected 6 PFAS [perfluorooctane sulfonate; perfluorooctanoate (PFOA); perfluorohexane sulfonate; perfluorononanoate; 2-(N-ethyl-perfluorooctane sulfonamido) acetate (EtFOSAA); 2-(N-methyl-perfluorooctane sulfonamide) acetate (MeFOSAA)] in >98 % of samples. Sixty percent of lactating women terminated breastfeeding by 9 months postpartum. Women with higher plasma concentrations of PFOA, EtFOSAA, and MeFOSAA had a greater hazard of terminating breastfeeding in the first 9 months postpartum [HR (95 % CI) per doubling concentration: 1.20 (1.04, 1.38) for PFOA; 1.10 (1.01, 1.20) for EtFOSAA; 1.18 (1.08, 1.30) for MeFOSAA]. In the quantile g-computation model, simultaneously increasing all PFAS in the mixture by one quartile was associated with 1.17 (95 % CI: 1.05, 1.31) greater hazard of terminating breastfeeding in the first 9 months. ConclusionOur findings suggest that exposure to PFAS may be associated with reduced breastfeeding duration and draw further attention to environmental chemicals that may dysregulate human lactation.

Associations of Gestational Perfluoroalkyl Substances Exposure with Early Childhood BMI -Scores and Risk of Overweight/Obesity: Results from the ECHO Cohorts.

Gestational per- and polyfluoroalkyl substances (PFAS) exposure may be associated with adiposity and increased risk of obesity among children and adolescents. However, results from epidemiological studies evaluating these associations are inconsistent. We estimated the associations of pregnancy PFAS concentrations with child body mass index (BMI) -scores and risk of overweight/obesity in eight U.S. cohorts. We used data from 1,391 mother-child pairs who enrolled in eight Environmental influences on Child Health Outcomes (ECHO) cohorts (enrolled: 1999-2019). We quantified concentrations of seven PFAS in maternal plasma or serum in pregnancy. We measured child weight and height between the ages of 2 and 5 y and calculated age- and sex-specific BMI -scores; 19.6% children had more than one BMI measurement. We estimated covariate-adjusted associations of individual PFAS and their mixture with child BMI -scores and risk of overweight/obesity using linear mixed models, modified Poisson regression models, and Bayesian approaches for mixtures. We explored whether child sex modified these associations. We observed a pattern of subtle positive associations of PFAS concentrations in pregnancy with BMI -scores and risk of overweight/obesity. For instance, each doubling in perfluorohexane sulfonic acid concentrations was associated with higher BMI -scores (; 95% CI: 0.01, 0.12). Each doubling in perfluroundecanoic acid [; 95% CI: 1.04, 1.16] and -methyl perfluorooctane sulfonamido acetic acid (; 95% CI: 1.00, 1.12) was associated with increased risk of overweight/obesity, with some evidence of a monotonic dose-response relation. We observed weaker and more imprecise associations of the PFAS mixture with BMI or risk of overweight/obesity. Associations did not differ by child sex. In eight U.S.-based prospective cohorts, gestational exposure to higher levels of PFAS were associated with slightly higher childhood BMI -score and risk of overweight or obesity. Future studies should examine associations of gestational exposure to PFAS with adiposity and related cardiometabolic consequences in older children. https://doi.org/10.1289/EHP11545.

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

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

Perfluorooctanoic acid dominates the molecular-level effects of a mixture of equal masses of perfluorooctanoic acid and perfluorooctane sulfonic acid in earthworm

Per- and polyfluoroalkyl substances (PFAS) are an important class of emerging contaminants in the environment. Most studies on the impact of PFAS mixtures considered phenotypic endpoints, which may not adequately reflect the sublethal effects on organisms. To fill this knowledge gap, we investigated the subchronic impact of environmentally relevant concentrations of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS)—as individual compounds and a mixture (PFOS+PFOA)—on earthworm (Eisenia fetida), using phenotypic and molecular endpoints. PFAS decreased the survival (12.2–16.3%), biomass (9.0–9.8%), and reproduction (15.6–19.8%) of E. fetida after 28 d of exposure. The bioaccumulation of PFOS after 28 d increased (from 2790.7 ng/g-dw to 5224.9 ng/g-dw) while that of PFOA decreased (from 780.2 ng/g-dw to 280.5 ng/g-dw) when E. fetida was exposed to the mixture compared to the individual compounds. These bioaccumulation trends were partly attributed to changes in the soil distribution coefficient (Kd) of PFOS and PFOA when present in the mixture. Eighty percent of the (p and FDR < 0.05) altered metabolites after 28 d were similarly perturbed by both PFOA and PFOS+PFOA. The pathways dysregulated are related to the metabolism of amino acids, energy, and sulfur. We showed that PFOA dominates the molecular-level impact of the binary PFAS mixture.

Prenatal exposures to per- and polyfluoroalkyl substances and epigenetic aging in umbilical cord blood: The Healthy Start study

BackgroundPer- and polyfluoroalkyl substances (PFAS) are ubiquitous, environmentally persistent chemicals, and prenatal exposures have been associated with adverse child health outcomes. Prenatal PFAS exposure may lead to epigenetic age acceleration (EAA), defined as the discrepancy between an individual's chronologic and epigenetic or biological age. ObjectivesWe estimated associations of maternal serum PFAS concentrations with EAA in umbilical cord blood DNA methylation using linear regression, and a multivariable exposure-response function of the PFAS mixture using Bayesian kernel machine regression. MethodsFive PFAS were quantified in maternal serum (median: 27 weeks of gestation) among 577 mother-infant dyads from a prospective cohort. Cord blood DNA methylation data were assessed with the Illumina HumanMethylation450 array. EAA was calculated as the residuals from regressing gestational age on epigenetic age, calculated using a cord-blood specific epigenetic clock. Linear regression tested for associations between each maternal PFAS concentration with EAA. Bayesian kernel machine regression with hierarchical selection estimated an exposure-response function for the PFAS mixture. ResultsIn single pollutant models we observed an inverse relationship between perfluorodecanoate (PFDA) and EAA (−0.148 weeks per log-unit increase, 95% CI: −0.283, −0.013). Mixture analysis with hierarchical selection between perfluoroalkyl carboxylates and sulfonates indicated the carboxylates had the highest group posterior inclusion probability (PIP), or relative importance. Within this group, PFDA had the highest conditional PIP. Univariate predictor-response functions indicated PFDA and perfluorononanoate were inversely associated with EAA, while perfluorohexane sulfonate had a positive association with EAA. ConclusionsMaternal mid-pregnancy serum concentrations of PFDA were negatively associated with EAA in cord blood, suggesting a pathway by which prenatal PFAS exposures may affect infant development. No significant associations were observed with other PFAS. Mixture models suggested opposite directions of association between perfluoroalkyl sulfonates and carboxylates. Future studies are needed to determine the importance of neonatal EAA for later child health outcomes.

Associations of prenatal and postnatal exposure to perfluoroalkyl substances with pubertal development and reproductive hormones in females and males: The HOME study

BackgroundPrenatal and childhood exposure to per- and polyfluoroalkyl substances (PFAS) may be associated with lower reproductive hormones and later puberty, but epidemiological studies evaluating these associations are scarce. ObjectivesWe examined associations of PFAS concentrations assessed from pregnancy to adolescence with pubertal development and reproductive hormones at age 12 years. MethodsWe studied 200 mother-child pairs from the HOME Study in Cincinnati, OH (enrolled: 2003–2006). We quantified serum concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), and perfluorohexane sulfonate (PFHxS) in pregnant women and their children at age 3, 8 and 12 years. At age 12 years, children self-assessed pubertal development using Tanner staging of pubic hair growth (males and females) and breast growth (females), and age at menarche. We quantified serum concentrations of dehydroepiandrosterone sulfate, luteinizing hormone, and follicle-stimulating hormone in both sexes; estradiol in females; testosterone in males. We estimated associations of PFAS with pubertal outcomes and reproductive hormones using a combination of ordinal regression, Cox proportional-hazard regression, and linear regression. Quantile-based g-computation was used for PFAS mixture. ResultsIn females, adolescent PFAS concentrations and their mixture were associated with later pubic hair growth, breast maturation, and age at menarche, but there was no pattern for prenatal or other postnatal concentrations. For instance, in females, each doubling in adolescent PFAS concentrations was associated with 79 % (PFOA), 63 % (PFOS), 56 % (PFNA), and 47 % (PFHxS) lower odds of attaining a higher stage for breast growth. In addition, adolescent PFAS concentrations were consistently associated with lower estradiol concentrations in females. No pattern was observed for associations of PFAS concentrations with pubic hair growth or reproductive hormones in males. ConclusionsWe observed associations between PFAS concentrations in adolescence and later pubertal development in females, but this could be due to reverse causation induced by excretion of PFAS through menstrual fluid.

Predicting Interfacial Tension and Adsorption at Fluid-Fluid Interfaces for Mixtures of PFAS and/or Hydrocarbon Surfactants.

Many per- and polyfluoroalkyl substances (PFAS) are surface-active and adsorb at fluid-fluid interfaces. The interfacial adsorption controls PFAS transport in multiple environmental systems, including leaching through soils, accumulation in aerosols, and treatment methods such as foam fractionation. Most PFAS contamination sites comprise mixtures of PFAS as well as hydrocarbon surfactants, which complicates their adsorption behaviors. We present a mathematical model for predicting interfacial tension and adsorption at fluid-fluid interfaces for multicomponent PFAS and hydrocarbon surfactants. The model is derived from simplifying a prior advanced thermodynamic-based model and applies to nonionic and ionic mixtures of the same charge sign with swamping electrolytes. The only required model inputs are the single-component Szyszkowski parameters obtained for the individual components. We validate the model using literature interfacial tension data of air-water and NAPL (non-aqueous phase liquid)-water interfaces covering a wide range of multicomponent PFAS and hydrocarbon surfactants. Application of the model to representative porewater PFAS concentrations in the vadose zone suggests competitive adsorption can significantly reduce PFAS retention (up to 7 times) at some highly contaminated sites. The multicomponent model can be readily incorporated into transport models to simulate the migration of mixtures of PFAS and/or hydrocarbon surfactants in the environment.

Per- and polyfluoroalkyl substances (PFAS) in mixtures show additive effects on transcriptomic points of departure in human liver spheroids.

Per- and polyfluoroalkyl substances (PFAS) are a wide range of chemicals that are used in a variety of consumer and industrial products leading to direct human exposure. Many PFAS are chemically nonreactive and persistent in the environment, resulting in additional exposure from water, soil, and dietary intake. While some PFAS have documented negative health effects, data on simultaneous exposures to multiple PFAS (PFAS mixtures) are inadequate for making informed decisions for risk assessment. The current study leverages data from previous work in our group using Templated Oligo-Sequencing (TempO-Seq) for high-throughput transcriptomic analysis of PFAS-exposed primary human liver cell spheroids; herein, we determine the transcriptomic potency of PFAS in mixtures. Gene expression data from single PFAS and mixture exposures of liver cell spheroids were subject to benchmark concentration (BMC) analysis. We used the 25th lowest gene BMC as the point of departure to compare the potencies of single PFAS to PFAS mixtures of varying complexity and composition. Specifically, the empirical potency of 8 PFAS mixtures were compared to predicted mixture potencies calculated using the principal of concentration addition (ie, dose addition) in which mixture component potencies are summed by proportion to predict mixture potency. In this study, for most mixtures, empirical mixture potencies were comparable to potencies calculated through concentration addition. This work supports that the effects of PFAS mixtures on gene expression largely follow the concentration addition predicted response and suggests that effects of these individual PFAS in mixtures are not strongly synergistic or antagonistic.

Mitochondrial dysfunction in metabolic disorders induced by per- and polyfluoroalkyl substance mixtures in zebrafish larvae

Several per- and polyfluoroalkyl substances (PFAS) have been linked to metabolic disorders in organisms. However, few studies have considered their combined effects, which would be more representative of PFAS occurring in the environment. In this study, zebrafish embryos were exposed to a mixture of 18 PFAS at three environmentally relevant concentrations for 5 days to assess their bioconcentration and metabolic consequences. The burdens of ∑PFAS in zebrafish larvae were 0.12, 1.58, and 9.63 mg/kg in the 0.5, 5, and 50 μg/L treatment groups, respectively. Exposure to the PFAS mixture accelerated hatching and larval heart rates, increased energy expenditure, and reduced ATP levels and glucose contents due to decreased feed intake and glucose uptake. Metabolomic analysis revealed that exposure to the PFAS mixture enhanced glycolysis but inhibited phospholipid synthesis, and significantly increased the expression of lipid metabolism related genes (srebf1, acox, and pparα), which indicated enhanced β-oxidation. The significant changes in mitochondrial membrane potential, mitochondrial content, and the transcription of genes involved in the mitochondrial respiratory chain (mfn2, ndufs1, atp5fa1, and mt-nd1) and mitochondrial DNA replication and transcription (18rs-rrn, and polg1) suggested that exposure to the PFAS mixture could cause mitochondrial dysfunction and further disrupt glucose and lipid metabolic pathways, ultimately causing metabolic disorders in zebrafish larvae. These findings demonstrate the importance of assessing the metabolic effects of PFAS mixtures on early development in wildlife and humans.

Per- and Polyfluoroalkyl Substances (PFAS) Mixture during Pregnancy and Postpartum Weight Retention in the New Hampshire Birth Cohort Study (NHBCS).

Per- and polyfluoroalkyl substances (PFAS), widely used in industrial and consumer products, are suspected metabolic disruptors. We examined the association between a PFAS mixture during pregnancy and postpartum weight retention in 482 participants from the New Hampshire Birth Cohort Study. PFAS concentrations, including perfluorohexane sulfonate, perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), and perfluorodecanoate, were quantified in maternal plasma collected at ~28 gestational weeks. Postpartum weight change was calculated as the difference between self-reported weight from a postpartum survey administered in 2020 and pre-pregnancy weight abstracted from medical records. Associations between PFAS and postpartum weight change were examined using Bayesian kernel machine regression and multivariable linear regression, adjusting for demographic, reproductive, dietary, and physical activity factors; gestational week of blood sample collection; and enrollment year. PFOS, PFOA, and PFNA were positively associated with postpartum weight retention, and associations were stronger among participants with a higher pre-pregnancy body mass index. A doubling of PFOS, PFOA, and PFNA concentrations was associated with a 1.76 kg (95%CI: 0.31, 3.22), 1.39 kg (-0.27, 3.04), and 1.04 kg (-0.19, 2.28) greater postpartum weight retention, respectively, among participants who had obesity/overweight prior to pregnancy. Prenatal PFAS exposure may be associated with increased postpartum weight retention.