Perfluorooctanoate Concentrations Research Articles

Association of diet with per- and polyfluoroalkyl substances in plasma and human milk in the New Hampshire Birth Cohort Study

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.

Perfluorooctanoate and nano titanium dioxide impair the byssus performance of the mussel Mytilus coruscus

Perfluorooctanoate (PFOA) is widely used as a surfactant and has metabolic, immunologic, developmental, and genetic toxicity on marine organisms. However, the effects of PFOA on individual defense functions in mussels in the presence of titanium dioxide nanoparticles (nano-TiO2) are poorly understood. To investigate the defense strategies and regulatory mechanisms of mussels under combined stressors, the thick-shell mussels Mytilus coruscus were exposed to different PFOA concentrations (0, 2 and 200 μg/L) and nano-TiO2 (0 and 0.1 mg /L, size: 25 nm) for 14 days. The results showed that, compared to the control group, PFOA and nano-TiO2 significantly reduced the number of byssal threads (NBT), byssal threads length (BTL), diameter of proximal threads (DPB), diameter of middle threads (DMB), diameter of distal byssal threads (DDB), adhesive plaque area (BPA), and breaking force of byssal threads (N). Under the influence of PFOA and nano-TiO2, the morphological surface smoothness of the fractured byssal threads surface increased, concurrently inducing an increased surface roughness in the adhesive plaques. Additionally, under the presence of PFOA and nano-TiO2, the foot displayed dispersed tissue organization and damaged villi, accompanied by an increased incidence of cellular apoptosis and an upregulation of the apoptosis gene caspase-8. Expression of the adhesion gene mfp-3 and byssal threads strength genes (preCOL-D, preCOL-NG) was upregulated. An interactive effect on the performance of byssal threads is observed under the combined influence of PFOA and nano-TiO2. Under co-exposure to PFOA and nano-TiO2, the performance of the byssal threads deteriorates, the foot structure is impaired, and the genes mRNA expression of byssal thread secretory proteins have compensated for the adhesion and byssal threads strength by up-regulation. Within marine ecosystems, organic and particulate contaminants exert a pronounced effect on the essential life processes of individual organisms, thereby jeopardizing their ecological niche within community assemblages and perturbing the dynamic equilibrium of the overarching ecosystem. Environmental ImplicationPerfluorooctanoic acid (PFOA) is prone to accumulate in marine organisms. TiO2 nanoparticles (nano-TiO2) are emerging environmental pollutants frequently found in marine environment. The effects of PFOA and nano-TiO2 on marine mussels are not well understood, and their toxic mechanisms remain largely unknown. We investigated the impacts of PFOA and nano-TiO2 on mussel byssus defense mechanisms. By assessing byssus performance indicators, morphological structures of the byssus, subcellular localization, and changes in byssal secretion-related genes, we revealed the combined effects and mechanisms through which these two types of pollutants may affect the functional capabilities and survival of mussels in the complex marine ecosystem.

Wavelength-dependent photoelectrochemical response demonstrated by the determination of acetaminophen and rutin in differential molecularly imprinted polymers strategy

Herein, the excitation wavelength-dependent responses of the molecularly imprinted polymer (MIP) photoelectrochemical (PEC) sensors were investigated, using acetaminophen (AP), rutin (RT) and perfluorooctanoate (PFOA) as the model templates, pyrrole as functional monomer, CuInS2@ZnS/TiO2 NTs as the basic photoelectrode. With wavelength λ > 240 nm, the photocurrent of MIPPFOA enhanced at higher concentrations of PFOA. With increasing AP concentration, the photocurrents of MIPAP could decline with λ < 271 nm, not change at λ = 270 nm, or increase with λ > 270 nm. As RT concentration increased, the photocurrents of MIPRT could decrease (λ < 431 nm), not change (λ = 431 nm) or increase (λ > 431 nm). The PEC responses depend on the comprehensive interaction of two contrary mechanisms from the template molecules within the MIP membrane. The photocurrent is enhanced by the role of the electron donor for photo-generated holes but attenuated due to the steric hindrance effect and the excitation light intensity loss via absorption or scattering. The apparent molar absorption coefficient of AP and RT within MIP membranes are 9.1–19.4 folds of those measured from dilute solutions. By using a routine UV lamp as the light source, the photocurrents of MIPRT at 254 nm and MIPAP at 365 nm were used to determine RT and AP, with the detection limits of 5.3 and 16 nM, respectively. The interference from the non-specific adsorption of interferents on the surfaces of MIPAP and MIPRT was reduced by one order of magnitude via a differential strategy.

Prenatal exposure to per- and polyfluoroalkyl substances and early childhood adiposity and cardiometabolic health in the Healthy Start study.

Observational and experimental studies have suggested that prenatal exposure to per- and polyfluoroalkyl substances (PFAS) can increase childhood adiposity and cardiometabolic disruption. However, most previous studies have used weight-based measures that cannot distinguish between fat mass and lean mass. We evaluated associations of prenatal PFAS exposure with precisely measured body composition and cardiometabolic biomarkers in early childhood. 373 eligible mother-infant pairs in the Healthy Start longitudinal cohort. We used multiple linear regression and Bayesian kernel machine regression models to estimate associations between five PFAS in maternal mid-pregnancy serum, and early childhood adiposity via air displacement plethysmography. Secondary outcomes included body mass index, waist circumference, and fasting serum lipids, glucose, insulin and adipokines. Models were adjusted for potential confounders and effect modification by child sex was evaluated. The median age of children at assessment was 4.6 years. Prenatal concentration of perfluorooctanoate (PFOA) was positively associated with percent fat mass (0.89% per log2-unit increase, 95% CI: 0.15, 1.64), while perfluorononanoate (PFNA) was positively associated with fat mass index and body mass index. Cardiometabolic markers in blood were generally not associated with prenatal PFAS in this population. Mixture models confirmed the importance of PFNA and PFOA in predicting percent fat mass, while PFNA was most important for fat mass index, body mass index, and waist circumference. There were no significant effects of the five PFAS as a mixture, potentially due to opposing effects of different PFAS. Our results agree with previous studies showing that prenatal serum concentrations of certain PFAS are positively associated with early childhood adiposity. Notably, associations were stronger for measures incorporating precisely measured fat mass compared to measures of body size or weight. Early life increases in adiposity may precede the development of adverse cardiometabolic health outcomes in children exposed to PFAS during gestation.

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 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.

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.

Perfluorinated compound correlation between human serum and drinking water: Is drinking water a significant contributor?

Perfluorinated compounds (PFASs) are a new artificial chemical. Due to its substantial toxicity and complex degradation in the natural environment, monitoring PFASs has become a hot issue for many researchers. Currently, the relationship between the concentration of PFASs in serum and the concentration of PFASs in drinking water is unclear. This paper aims to study the concentration levels of PFASs in drinking water and residents' serum in a city in northern China and the relationship between them. The results show that the concentration of PFASs in drinking water is low, and the average concentrations of perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) were 2.57 ± 0.69 ng/L and 0.30 ng/L, respectively, which were lower than the limits specified in China's newly introduced Standards for drinking water quality (GB 5749-2022). In the serum of residents, PFOA and PFOS were the two PFASs with the highest concentration. Spearman correlation analysis showed that perfluorohexane sulfonate (PFHxS) and PFOS concentrations were positively correlated with age, and PFHxS, PFOA, PFNA, and PFOS varied with sex. At the same time, the correlation analysis also showed no correlation between PFAS in drinking water and serum, indicating that drinking water was not the main factor causing the physical burden of PFAS in residents. The HI method was used to assess the health risks of PFASs to human beings. The risk entropy of all PFASs for human hepatotoxicity and reproductive toxicity is below 1.

Concentrations of Per- and Polyfluoroalkyl Substances in Paired Maternal Plasma and Human Milk in the New Hampshire Birth Cohort.

Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent endocrine-disrupting chemicals associated with long-term health outcomes. PFAS are transferred from maternal blood to human milk, an important exposure source for infants, and understanding of this transfer is evolving. We characterized concentrations of 10 PFAS in human milk (n = 426) and compared milk-to-plasma concentrations of 9 PFAS among a subset of women with paired samples (n = 294) from the New Hampshire Birth Cohort Study using liquid chromatography-isotope dilution tandem mass spectrometry. We examined the relationship between perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) in plasma versus milk and fit linear regression models to assess relationships between milk PFOA and PFOS and participant characteristics. The median plasma PFOA concentration was 0.94 ng/mL (interquartile range, IQR, 0.59-1.34) and that of PFOS was 2.60 ng/mL (IQR 1.80-3.90); the median milk PFOA concentration was 0.017 ng/mL (IQR 0.012-0.027) and that of PFOS was 0.024 ng/mL (IQR 0.016-0.036). PFOA and PFOS plasma and milk concentrations showed correlations of ρ = 0.83 and 0.77, respectively (p < 0.001). Parity, previous lactation, week of milk collection, and body mass index were inversely associated with milk PFAS. We estimate that even among our general population cohort, some infants (∼6.5%) are exposed to amounts of PFAS via milk that may have long-term health impacts.

Uptake, accumulation, and toxicity of per- and polyfluoroalkyl substances in Allium cepa grown in soils amended with biosolids

Uptake and accumulation of per- and polyfluoroalkyl substances (PFAS) in Allium cepa from soils amended with biosolids were investigated. The Ʃ38 PFAS concentrations in soils amended with biosolids ranged from 10.4 to 104 ng g−1 (dry-weight). Among PFAS, perfluorooctanesulfonate (PFOS) concentration was the highest in soils, with a maximum of 48.1 ng g−1, followed by N-ethylperfluoro-1-octanesulfonamidoacetic acid (N-Et-FOSAA) with the maximum of 10.9 ng g−1. The concentration of perfluorooctanoate (PFOA) was higher (0.55–1.82 ng g−1) in roots of A. cepa than that of PFOS (0.03–0.13 ng g−1). The accumulation of PFAS in A. cepa shoots depended on the carbon chain length, with a more significant accumulation of shorter C-chain PFAS than the longer C-chain derivatives. The concentration of PFAS in shoots correlated positively with corresponding root concentration, suggesting a significant translocation of PFAS from root to shoots. A. cepa showed no considerable cyto-genotoxicity in the meristem root tip cells exposed to soils amended with biosolids. The oxidative stress parameters such as reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and lipid peroxidation (LP) showed no significant change over control in A. cepa root cells exposed to soils amended with biosolids. The estimated dietary intake for PFOA and PFOS did not exceed the recommended tolerable daily intake (TDI) even after assuming that onion accounted for 100% of vegetable consumption. This study provides evidence of accumulation and translocation of PFAS from soil to roots and shoots of A. cepa. Also, we assessed the potential risk of PFAS accumulated in A. cepa to humans via the food chain to be insignificant.

Microcosm experiment to test bacterial responses to perfluorooctanoate exposure

The impact of perfluoroalkyl and polyfluoroalkyl substances on microbial communities is challenging to investigate in situ because of the complexity and dynamics of natural ecosystems. In the present study, four microcosms were established to explore the impact of perfluorooctanoate (PFOA) on bacterial communities in riverine and marine settings. PFOA distribution between the aqueous and sedimentary phases fluctuated in both PFOA-amended and unamended control systems. PFOA was more rapidly partitioned into the sediment in marine than in riverine microcosms. Differences in iron concentration and salinity may influence PFOA exchange between water and sediment. In marine microcosms, the alpha diversity of bacterial communities was significantly correlated to PFOA concentration. PFOA tended to correlate more strongly with bacterial community composition in water than in sediment. At the whole system level, Lefse's analysis indicated Algoriphagus halophilus as biomarkers for PFOA exposure in both riverine and marine systems, and the family Flavobacteriaceae were also more abundant in the exposed systems. In terms of temporal variation (comparison between three time points in the systems), metastat analysis showed great variability of potential PFOA-sensitive bacteria at the genus level. As such, most PFOA-sensitive genera were transitory and variable and existed for a short term in different systems (river, sea, blank, and experiment) and phases. Compared with other PFOA-sensitive genera, we suggest that further research is carried out to explore the use of Limnobacter as a bioindicator for temporal monitoring of PFOA pollution.

Gestational per- and polyfluoroalkyl substances exposure and infant body mass index trajectory in the New Hampshire Birth Cohort Study

Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent, potential metabolic disruptors of concern for infants. Mothers participating in the New Hampshire Birth Cohort Study (NHBCS) provided a plasma sample during pregnancy to measure concentrations of seven PFAS, and infant weight and length were abstracted from well-child visits between birth and 12 months.Sex-specific growth patterns of child body mass index (BMI) were fit using a growth mixture model (GMM) and the relative risk ratios (RRR) and 95% Confidence Intervals (95% CI) for the association of maternal plasma PFAS with BMI growth patterns during infancy were estimated by using multinomial logistic model for the group probabilities in the GMM.Four growth patterns were identified: Group 1) a steep increase in BMI during the first 6 months, then a leveling off; Group 2) a gradual increase in BMI across the year; Group 3) a steep increase in BMI during months 1–3, then stable BMI; and Group 4) a gradual increase in BMI with plateau around 3 months (reference group). For boys, higher maternal pregnancy perfluorooctanoate concentrations were associated with a 60% decreased chance of being in group 3 as compared to group 4, after adjusting for potential confounding variables (RRR = 0.4; 95% CI: 0.1, 0.9). For girls, higher maternal perfluorooctane sulfonate (PFOS) concentrations during pregnancy were associated with a higher likelihood of following the growth pattern of groups 2 (RRR = 2.5; 95% CI: 1.0, 6.1) and 3 (RRR = 2.8; 95% CI: 1.0, 7.6) as compared to group 4, adjusting for potential confounding variables.In this cohort, sex-specific associations of maternal plasma PFAS concentrations during pregnancy with growth patterns during the first year of life were observed, with greater BMI growth observed among infant girls born to mothers with higher pregnancy concentrations of PFOS.

Perfluorooctanoate and perfluorooctane sulfonate in umbilical cord blood and child cognitive development: Hamamatsu Birth Cohort for Mothers and Children (HBC Study)

BackgroundPrenatal exposure to per- and polyfluoroalkyl substances (PFAS) has been shown to affect offspring behaviors in laboratory animals. Several epidemiological studies investigated associations between prenatal PFAS exposure and child neurodevelopment, but results were inconclusive. We examined associations between cord blood concentrations of perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) and cognitive development in children from 4 to 40 months of age. MethodsThis study included 598 mother–child pairs who participated in the Hamamatsu Birth Cohort Study for Mothers and Children (HBC Study), a prospective birth cohort study in Japan. PFOA and PFOS were quantified in cord blood. The Mullen Scales of Early Learning (MSEL) was used to assess child cognitive function at 4, 6, 10, 14, 18, 24, 32, and 40 months of age. For each of log 2-transformed PFOA and PFOS concentrations, we examined: 1) associations with the scores of MSEL Early Learning Composite (Composite) and four subscales (Fine Motor, Visual Reception, Receptive Language, Expressive Language) at each assessment time point; and 2) associations with longitudinal changes in the Composite and subscale scores. ResultsMSEL Composite scores were inversely associated with PFOA at 18 months of age (per 2-fold increase in concentration: β = -2.23, 95% CI: -3.91, -0.56), but not at other ages. When accounting for changes in scores from 4 to 40 months of age, PFOA and PFOS were positively associated with Composite as well as Receptive and Expressive Language scores. Child’s sex modified associations between PFOA and Composite scores at 14, 18, and 40 months and those between PFOS and Composite scores at 14 months, showing negative associations among females. ConclusionsIn this study, cord blood PFOA and PFOS concentrations showed mixed associations with child cognitive functions at specific age but had positive associations with longitudinal changes in cognitive development from 4 to 40 months of age.

Per-/polyfluoroalkyl substance concentrations in human serum and their associations with immune markers of rheumatoid arthritis

Per-/polyfluoroalkyl substances (PFASs) are ubiquitous in the environment and have been proved to be immunotoxic to humans. However, it remains unclear whether exposure to PFASs affects the risk of rheumatoid arthritis (RA). In this study, nine PFASs were determined in human serum collected from 280 health populations and 294 RA patients in a cohort enrolled between 2018 and 2020 in Hangzhou, China, and were examined their correlations with immune marker levels. Perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), and 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) were the predominant PFASs in human serum, with median (mean) concentrations of 5.4 (7.6), 2.8 (3.5), and 1.9 (2.5) ng/mL, respectively. Serum PFOA and 6:2 Cl-PFESA concentrations were positively correlated with anti-cyclic citrullinated peptide antibody (ACPA) (βPFOA = 0.59, 95% confidence interval (CI): 0.37, 0.81; β6:2 Cl-PFESA = 0.48, 95% CI: 0.29, 0.66), immunoglobulin G (βPFOA = 0.25, 95% CI: 0.21, 0.29; β6:2 Cl-PFESA = 0.16, 95% CI: 0.12, 0.19) as well as rheumatoid factors (RF) (βPFOA = 0.57, 95% CI: 0.34, 0.80; β6:2 Cl-PFESA = 0.54, 95% CI: 0.36, 0.72). The correlations between serum PFOS levels and RF (β = 0.52, 95% CI: 0.28, 0.77), ACPA (β = 0.48, 95% CI: 0.23, 0.73), as well as immunoglobulin M (β = −0.24, 95% CI: 0.64, 0.15) respectively were statistically stronger. We also found PFOA concentrations in serum were associated with the level of C-reactive protein (β = 0.52, 95% CI: 0.40, 0.65). To our knowledge, this is the first study reporting significant associations between several PFASs and change of specific immune marker levels, suggesting that PFAS exposure may increase the risk of RA in adults.

Gestational Perfluoroalkyl Substance Exposure and DNA Methylation at Birth and 12 Years of Age: A Longitudinal Epigenome-Wide Association Study.

Background:DNA methylation alterations may underlie associations between gestational perfluoroalkyl substances (PFAS) exposure and later-life health outcomes. To the best of our knowledge, no longitudinal studies have examined the associations between gestational PFAS and DNA methylation.Objectives:We examined associations of gestational PFAS exposure with longitudinal DNA methylation measures at birth and in adolescence using the Health Outcomes and Measures of the Environment (HOME) Study (2003–2006; Cincinnati, Ohio).Methods:We quantified serum concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), and perfluorohexane sulfonate (PFHxS) in mothers during pregnancy. We measured DNA methylation in cord blood () and peripheral leukocytes at 12 years of age () using the Illumina HumanMethylation EPIC BeadChip. We analyzed associations between PFAS concentrations and repeated DNA methylation measures using linear regression with generalized estimating equations. We included interaction terms between children’s age and gestational PFAS. We performed Gene Ontology enrichment analysis to identify molecular pathways. We used Project Viva (1999–2002; Boston, Massachusetts) to replicate significant associations.Results:After adjusting for covariates, 435 cytosine–guanine dinucleotide (CpG) sites were associated with PFAS (false discovery rate, ). Specifically, we identified 2 CpGs for PFOS, 12 for PFOA, 8 for PFHxS, and 413 for PFNA; none overlapped. Among these, 2 CpGs for PFOA and 4 for PFNA were replicated in Project Viva. Some of the PFAS-associated CpG sites annotated to gene regions related to cancers, cognitive health, cardiovascular disease, and kidney function. We found little evidence that the associations between PFAS and DNA methylation differed by children’s age.Discussion:In these longitudinal data, PFAS biomarkers were associated with differences in several CpGs at birth and at 12 years of age in or near genes linked to some PFAS-associated health outcomes. Future studies should examine whether DNA methylation mediates associations between gestational PFAS exposure and health. https://doi.org/10.1289/EHP10118

Gestational Perfluorooctanoate Exposure and Childhood Metabolome at Age 8 Years

BACKGROUND AND AIM: Gestational exposure to perfluorooctanoate (PFOA) is associated with excess adiposity and increased cardiometabolic risk in children. To identify potential mechanisms underlying these associations, we characterized metabolic alterations and pathways associated with gestational PFOA exposure in 8-year-old children using a metabolome-wide association study (MWAS). METHODS: METHODS: We performed untargeted, high-resolution metabolomic profiling of serum samples collected at age 8-years from 106 children enrolled in the HOME study (Cincinnati, OH) using high-resolution liquid chromatography mass spectrometry (LC-MS). During pregnancy, we quantified PFOA concentrations in serum collected from their mothers using LC-MS methods. Associations between maternal PFOA concentrations during pregnancy and annotated metabolites detected in child serum samples were evaluated using multivariable linear regression adjusted for child age, sex, and race with a false discovery rate 20%. Pathway level changes were determined by characterizing metabolite networks; enriched pathways were determined using Mummichog. RESULTS:Maternal PFOA concentrations during pregnancy (median: 5.2 ng/mL, 25th-75th percentile: 3.6-7.3 ng/mL) were associated with alterations in the child metabolome at age 8 years. Associations that met FDR20% included 203 metabolites, of which 144 were negatively associated with PFOA concentrations. Annotation of metabolites included a range of lipids and dietary factors, while pathway enrichment identified alterations in amino acid metabolism, lipid pathways, oxidative stress, de novo fatty acid biosynthesis and catabolism. CONCLUSIONS:This is the first study to examine gestational PFOA in association with childhood metabolome using untargeted approach. In this study, maternal PFOA concentrations at pregnancy were associated with systemic alterations in metabolic pathways related to energy production, oxidative stress and catabolism in serum collected from 8-year-old children. These results highlight the importance of early life exposure, and suggest that PFOA-related metabolic alterations manifest early in life. Future studies should examine how these PFOA-related alterations contribute to increased risk for childhood adiposity and cardiometabolic risk. KEYWORDS: PFAS, Metabolomics, Children's environmental health

Pregnancy per- and polyfluoroalkyl substances (PFAS) and hypertensive disorders of pregnancy in the Project Viva cohort

BACKGROUND AND AIM: Exposure to environmental chemicals may increase the risk of cardiovascular disease. However, data on associations between per- and polyfluoroalkyl substances (PFASs) and hypertensive disorders of pregnancy (HDP) are limited and inconsistent. We sought to determine the extent to which early-pregnancy PFAS concentrations are prospectively associated with HDP risk in a large cohort. METHODS: We studied 1,537 pregnant women from the Project Viva cohort in Boston, Massachusetts, USA. Using maternal plasma samples collected from 1999-2002 at a median of 9.7 gestational weeks, we quantified concentrations of eight PFAS [perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorohexane sulfonate (PFHxS), perfluorononanoate (PFNA), 2-(N-ethyl-perfluorooctane sulfonamide) acetate (EtFOSAA), 2-(N-methyl-perfluorooctane sulfonamide) acetate (MeFOSAA), perfluorodecanoate (PFDeA), perfluorooctane sulfonamide (FOSA)]. PFDeA and FOSA were detected in 50% of samples and were not included in further analyses. We assessed HDP using clinical data and defined preeclampsia and gestational hypertension according to the National High Blood Pressure Education Program recommendations. We used multinomial logistic regression to estimate associations of log2-transformed continuous PFAS concentrations with categories of HDP [gestational hypertension, preeclampsia, normotensive (ref)], adjusting for age, race/ethnicity, education, smoking, marital status, and parity. RESULTS:A total of 56 (4%) of women developed preeclampsia and 106 (7%) developed gestational hypertension. We observed higher risk of gestational hypertension per doubling of concentrations of PFOS (odds ratio [OR] 1.28, 95% confidence interval [CI]: 0.96, 1.70), PFOA (OR 1.36, 95% CI: 0.99, 1.86), and PFHxS (OR 1.22, 95% CI: 1.01, 1.48). Associations with other PFAS were consistent in direction but smaller in magnitude (e.g., EtFOSAA: OR 1.14, 95% CI: 0.95, 1.38). We did not observe associations between PFAS concentrations and preeclampsia. CONCLUSIONS:Our results support the hypothesis that PFAS exposure during pregnancy may increase the risk of gestational hypertension. However, we did not observe associations between PFAS exposure and preeclampsia. KEYWORDS: PFAS, hypertensive disorders of pregnancy, gestational hypertension, preeclampsia, pregnancy

Longitudinal analysis of DNA methylation in relation to gestational perfluoroalkyl substance exposure: An epigenome-wide association study

BACKGROUND AND AIM: Alterations to DNA methylation may underlie the association between gestational exposure to perfluoroalkyl substances (PFAS) and adverse health outcomes in children. However, few studies have examined the association between gestational PFAS exposure and DNA methylation, and no studies have repeated DNA methylation data across childhood. We examined associations between gestational PFAS exposure and repeated measures of offspring peripheral leukocyte DNA methylation among 266 mother-child pairs enrolled in the HOME Study (Cincinnati, OH). METHODS: We quantified serum concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), and perfluorohexane sulfonate (PFHxS) in mothers at ~16 weeks gestation. We measured DNA methylation at delivery (cord blood) and age 12 years using the Illumina HumanMethylation EPIC BeadChip. We analyzed the associations between log2-transformed PFAS concentrations and repeated DNA methylation measures using generalized estimating equations. Visit by PFAS interaction terms were used to test the stability of these differences across time. We performed Gene Ontology (GO) enrichment analysis to identify significant biological pathways. RESULTS:A total of 35 loci were significantly associated with PFAS (false discovery rate, q 0.05). Among the 5 loci for PFOS, 10 for PFOA, 7 for PFHxS, and 13 for PFNA (q 0.01), none overlapped. These loci mapped to genes (e.g., AGAP1, HPSE2, HABP2, RNF13, RADIL, and TMEM56) that are associated with cancers, cardiovascular disease, and cognitive function. We found little evidence that associations between PFAS and DNA methylation changed over time. The most significant GO pathways included homophilic cell adhesion, cell-cell adhesion and integral component of plasma membrane. CONCLUSIONS:Using longitudinal data, we identified loci associated with PFAS that have not been reported. Several loci were in genes linked to PFAS-associated health outcomes. Future studies are needed to confirm our findings and examine whether DNA methylation mediates associations between gestational PFAS exposure and offspring health. KEYWORDS: PFAS, Epigenomics, Biomarkers of exposure, Environmental epidemiology

Serum levels of perfluorooctanoic acid and perfluorooctane sulfonic acid in pregnant women: Maternal predictors and associations with birth outcomes in the PIPA Project.

Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) are persistent pollutants associated with adverse birth outcomes. This study aimed to identify predictors of blood PFOA and PFOS concentrations in pregnant women and to estimate their associations with birth outcomes in Brazil. We conducted a cross-sectional study with 139 pregnant women enrolled in the pilot study of the Rio Birth Cohort Study on Environmental Exposure and Childhood Development (PIPA Project). Multiple linear regression was used to estimate associations between PFOA and PFOS with maternal predictors and birth outcomes. Higher levels of PFOA were observed in women aged 16-19 and 20-39 years, while fish consumption from 0.6 to 2.0 times per week was associated with lower levels of the substance. PFOS levels were higher in women living in houses with up to four rooms but lower in those who reported passive exposure to smoking. Increased newborn length and head circumference were also associated with higher maternal levels of PFOA. In our study, age, fish consumption, passive smoking, and the number of rooms in the house were predictors of maternal PFAS levels. However, we did not observe significant associations between maternal plasma PFAS concentrations and birth outcomes.

Legacy and Emerging Poly- and Perfluoroalkyl Substances in Finless Porpoises from East China Sea: Temporal Trends and Tissue-Specific Accumulation.

Perfluoroalkyl sulfonates (PFSAs), perfluoroalkyl carboxylates (PFCAs), and emerging alternatives and precursors of these compounds were determined in tissues of finless porpoise (Neophocaena asiaeorientalis sunameri) collected from East China Sea in 2009-2010 and 2018-2019. The median hepatic concentrations of emerging poly- and perfluoroalkyl substances (PFASs), including 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), 8:2 chlorinated polyfluorinated ether sulfonate (8:2 Cl-PFESA), 2,3,3,3-tetrafluoro-2-propanoate (HFPO-DA), and 4,8-dioxa-3H-perfluorononanoate (ADONA) were 16.2, 2.16, < LOQ (limit of quantification) and < LOQ ng/g ww (wet weight), respectively. The concentrations of legacy substances, perfluorooctanesulfonate (PFOS), and perfluorooctanoate (PFOA), were 86.9 and 1.95 ng/g ww, respectively. The liver concentrations of 6:2 Cl-PFESA, HFPO-DA, and perfluorohexanesulfonate (PFHxS) increased with time between 2009-2010 and 2018-2019. Further, concentrations of PFOA showed a declining trend in finless porpoise, whereas PFOS and its precursor (i.e., perfluorooctane sulfonamide [FOSA]) showed an increasing trend with time between 2009-2010 and 2018-2019. Analysis of PFASs in nine different tissues/organs of finless porpoise (i.e., liver, heart, intestine, spleen, kidney, stomach, lung, muscle, and skin) revealed a similar distribution pattern between 6:2 Cl-PFESA and PFOS; however, the tissue distribution patterns differed between HFPO-DA and PFOA. The concentrations of PFAS alternatives in kidney were similar or lower than the prototype compounds PFOS and PFOA (i.e., 8:2 Cl-PFESA < 6:2 Cl-PFESA ≈ PFOS; HFPO-DA < PFOA), implying slow renal excretion of PFAS alternatives as that of legacy PFASs. The estimates of body burdens of PFASs in porpoises suggested comparable accumulation of PFAS alternatives and legacy PFSAs and PFCAs. This study provides novel information on temporal trends and tissue distribution of emerging PFASs in marine mammals in China.