Serum Polyfluoroalkyl Substances Research Articles

Self-Collection Blood Test for PFASs: Comparing Volumetric Microsamplers with a Traditional Serum Approach.

A remote sampling approach was developed at Eurofins for quantifying per- and polyfluoroalkyl substances (PFASs) in whole blood samples collected using volumetric absorptive microsamplers (VAMSs), which allow for self-collection of blood using a finger prick. This study compares PFAS exposure measured by self-collection of blood using VAMSs to the standard venous serum approach. Blood samples were collected from participants (n = 53) in a community with prior PFAS drinking water contamination using a venous blood draw as well as participant self-collection using VAMSs. Whole blood from the venous tubes was also loaded onto VAMSs to compare differences in capillary vs venous whole blood PFAS levels. Samples were quantified for PFASs using liquid chromatography tandem mass spectrometry and online solid-phase extraction. PFAS levels in serum were highly correlated with measurements in capillary VAMSs (r ≥ 0.91 and p < 0.05). Serum PFAS levels were generally twofold higher than whole blood, reflecting expected differences in their composition. Of interest, FOSA was detected in whole blood (both venous and capillary VAMSs) but not in serum. Overall, these findings indicate that VAMSs are useful self-collection tools for assessing elevated human exposure to PFASs.

Maternal Serum, Cord and Human Milk Levels of Per- and Polyfluoroalkyl Substances (PFAS), Association with Predictors and Effect on Newborn Anthropometry.

The understanding of per- and polyfluoroalkyl substances (PFAS) health effects is rapidly advancing among critical populations. Therefore, the objective of this study was to assess PFAS serum levels among Lebanese pregnant women, cord serum and human milk levels, their determinants, and effects on newborn anthropometry. We measured concentrations of six PFAS (PFHpA, PFOA, PFHxS, PFOS, PFNA and PFDA) using liquid chromatography MS/MS for 419 participants, of which 269 had sociodemographic, anthropometric, environmental and dietary information. The percentage of detection for PFHpA, PFOA, PFHxS and PFOS was 36.3-37.7%. PFOA and PFOS levels (95th percentile) were higher than HBM-I and HBM-II values. While PFAS were not detected in cord serum, five compounds were detected in human milk. Multivariate regression showed that fish/shellfish consumption, vicinity to illegal incineration and higher educational level were associated with an almost twice higher risk of elevated PFHpA, PFOA, PFHxS and PFOS serum levels. Higher PFAS levels in human milk were observed with higher eggs and dairy products consumption, in addition to tap water (preliminary findings). Higher PFHpA was significantly associated with lower newborn weight-for-length Z-score at birth. Findings establish the need for further studies, and urgent action to reduce exposure among subgroups with higher PFAS levels.

Community-facing toxicokinetic models to estimate PFAS serum levels based on life history and drinking water exposures

BackgroundPer- and polyfluoroalkyl substances (PFAS) are drinking water contaminants. Tools to assess the potential body burden associated with drinking PFAS-contaminated water may be helpful for public health assessment of exposed communities. MethodsWe implemented a suite of one-compartment toxicokinetic models using extensively calibrated toxicokinetic parameters (half-life and volume of distribution). We implemented the models both in the R programming language for research purposes, and as a web estimator for the general public (built in typescript.js). These models simulate exposure to PFAS water concentrations for individuals with varying characteristics such as age, sex, weight, and breastfeeding history. The models account for variability and uncertainty in parameter inputs to produce Monte Carlo-based estimates of serum concentration. For children, the models additionally account for gestational exposure, lactational exposure, and potential exposure through formula feeding. For adults who have borne children, the models account for clearance through birth and breastfeeding. We ran simulations of individuals with known PFAS water and serum concentrations to evaluate the model. We then compared the predicted serum PFAS concentrations to measured data. ResultsThe models accurately estimate individual-level serum levels for each PFAS for most adults within ½ order of magnitude. We found that the models somewhat overestimated serum concentrations for children in the tested locations, and that these overestimates are generally within an order of magnitude. DiscussionThis paper presents scientifically robust models that allow users to estimate serum PFAS concentrations based on known PFAS water concentrations and physiologic information. However, accuracy in historical water concentration inputs, exposure from non-drinking water sources, and life-history characteristics of individuals present a complex problem for individual estimation. Additional refinements to the model suite to improve the prediction of individual results may consist of including duration of exposure and additional life-history characteristics.

Prenatal exposure to per- and polyfluoroalkyl substances and pregnancy outcome in Austria

Per- and polyfluoroalkyl substances (PFAS) are a large group of persistent industrial chemicals that can harm reproductive health. PFAS levels were analysed to determine the current sources of exposure and possible associations between prenatal PFAS exposure and adverse pregnancy outcome. Samples from 136 mother-newborn pairs recruited between 2017 and 2019 were analysed for the presence of 31 target PFAS in maternal serum, umbilical cord serum, and placental tissue by high-performance liquid chromatography coupled to a tandem mass spectrometer. Questionnaires and medical records were used to survey sources of exposure and pregnancy outcome, including small for gestational age (SGA), fetal growth restriction (FGR), preeclampsia (PE), preterm birth, large for gestational age (LGA) and gestational diabetes mellitus (GDM). Data were analysed for individual PFAS and sum4PFAS (sum of perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonate (PFHxS), and perfluorooctane sulfonate (PFOS) serum levels) in logistic regression analyses and categorical regression analyses. Compared to data from a previous Viennese study in 2010–12, sum4PFAS levels were generally lower. Sum4PFAS serum levels of three women (2.2%) exceeded 6.9 µg/L, a level that corresponds to the recently established tolerable weekly intake (TWI) of EFSA for nursing mothers aged 35 years; in the 2010/2012 study it was 13.6%. The large contribution of unidentified extractable organofluorine (EOF) fractions to total PFAS exposure is a concern. Study site, mean maternal corpuscular hemoglobin (MCH), use of facial lotion, and owning upholstered furniture were significantly influencing maternal exposure. While no effect of sum4PFAS on pregnancy outcome could be detected, we found highest placental PFDA levels in SGA births. PFHxS levels in umbilical cord and placenta were highest in preterm births. Further studies are needed to elucidate the relationship of prenatal PFAS exposure and pregnancy outcome, in particular to confirm whether and how placental PFDA levels may contribute to an increased risk for SGA.

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

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

Associations between serum per- and polyfluoroalkyl substances and asthma morbidity in the National Health and Nutrition Examination Survey (2003-18).

Per- and polyfluoroalkyl substances (PFAS) are a class of chemicals widely used in manufacturing and are highly resistant to degradation, so they accumulate in the environment. Serum concentrations of these so-called forever chemicals have been associated with impairment of innate and adaptive immune responses. The relationship between serum PFAS levels and asthma morbidity has not been studied. We tested the association between serum PFAS concentration and asthma exacerbations. We performed secondary analysis of data from the National Health and Nutrition Examination Survey (NHANES, 2003-18). We fit multivariable logistic regression models to estimate odds ratios and 95% CIs for asthma exacerbation in the prior 12 months, given serum concentrations of PFAS. Models were adjusted for relevant covariates. Of 1101 participants with self-reported current asthma and available serum PFAS data, we observed that higher serum perfluorooctanoic and perfluorodecanoic acids were associated with greater odds of asthma attacks in the previous 12 months (respectively, adjusted odds ratio 1.16, 95% CI 1.01, 1.33; and adjusted odds ratio 1.21, 95% CI 1.03, 1.43). After stratification by age, the association between perfluorooctanoic acid and asthma attacks was significant in the 12-18-year-old group only (adjusted odds ratio 1.56, 95% CI 1.06, 2.31). No significant relationships were observed between PFAS and asthma-related emergency department visits. After correction for multiple comparison testing, none of the associations reached the threshold of significance. The role of these bioaccumulative forever chemicals in susceptibility to asthma attacks warrants further examination in longitudinal studies. (J Allergy Clin Immunol Global 2023;2:100078.).

Per- and polyfluoroalkyl substances (PFAS) and immune system-related diseases: results from the Flemish Environment and Health Study (FLEHS) 2008–2014

BackgroundThe successive FLEHS campaigns assess internal exposure to pollutants and associated early biological and health effects in participants of different age groups.Materials and methodsMother–newborn pairs (N = 220 in 2008–2009, age 18–42 years; N = 269 in 2013–2014, age 18–44 years), 197 adolescents 14–15 years (2010–2011), 201 adults 20–40 years (2008–2009) and 205 adults 50–65 years (2014) were recruited. For the various groups of subjects different sets of PFAS were assessed. Perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorobutane sulfonate (PFBS) were determined in cord plasma and peripheral serum as these were the PFAS compounds for which we had access to high quality measurements and which were expected to be present in the highest concentrations. Participants filled out a questionnaire based on the European Community Respiratory Health Survey questionnaire on asthma and allergy. In these cross-sectional studies associations were assessed using stepwise multiple logistic regression, with confounders (including smoking and familial occurrence of the disease) and potential covariates selected on the basis of experience in our previous studies and a literature search. Forest plots of odds ratios summarize the associations between the various PFAS on the one hand and the different immune outcomes on the other hand.ResultsFor several self-reported immune system-related diseases inverse associations with PFAS serum concentrations were observed. These inverse associations were more pronounced in mothers and adults than in adolescents. A significant inverse association was observed in adults and mothers (for mothers based on measurements on cord plasma) between PFNA, PFOS, and PFHxS and asthma (for mothers also for PFOA), in mothers between PFHxS, PFNA and PFOS and allergic rhinitis, in mothers and adults between PFHxS and PFOS and some forms of allergy (for mothers also for PFOA), in adults between PFOA and eczema, and in adolescents between PFOS and systemic allergy.ConclusionInternal exposure to PFAS was associated with changes in immunological processes consistent with what has been reported in the literature. Whereas these changes were observed in many publications to be associated with adverse health effects, our findings suggest that they can also lead to inverse associations with certain immune system-related diseases.

The exposure of Czech firefighters to perfluoroalkyl substances and polycyclic aromatic hydrocarbons: CELSPAC – FIREexpo case-control human biomonitoring study

The CELSPAC – FIREexpo biomonitoring study investigates the long-term effects of chemical exposure on firefighters' wellness and fitness. It aims to provide science-based measures to minimize the health risks of the firefighting occupation. Here, we present the study design, cohort profile, and first results with respect to internal per- and polyfluoroalkyl substances (PFAS) and polycyclic aromatic hydrocarbons (PAH) levels in study participants. Participants (n = 166) were divided into three subcohorts: i) newly recruited firefighters, ii) professional firefighters with several years' experience, and iii) the control group. Participants underwent physical performance tests, provided information on their lifestyle and diet, and urine and blood samples 1–4 times within an 11-week period. 12 serum PFAS and 10 urinary hydroxylated PAH (OH-PAH) levels were determined using HPLC-MS/MS and compared between subcohorts and samplings. The association of internal exposure with reported lifestyles and occupational factors was investigated using Spearman's correlation, principal component analysis, and multivariate regression analysis. ΣPFAS levels in firefighters were significantly higher than in the control group and were mostly associated with the length of firefighting career, age, blood donation, and population size. 10.9 % and 7.6 % of measurements exceeded the HBM-I or HBM-II value for PFOS and PFOA, respectively. Urinary ΣPAH levels increased significantly after training with burning wooden pallets, but none of them exceeded the no observed genotoxic effect level. Firefighters’ occupational exposure, its sources, and pathways, need to be systematically monitored and investigated on a long-term and individual basis. The CELSPAC – FIREexpo study helps to clarify the degree of occupational exposure to the given compounds and the subsequent risks to firefighters.

Per- and polyfluoroalkyl substances: using comparative medicine to understand exposure and adverse health outcomes in people and their pets.

One of the important human health benefits of keeping pets may be to serve as an early warning system for indoor childhood exposure to toxic chemicals such as per- and polyfluoroalkyl substances (PFAS). The stain-resistant properties and environmental stability of PFAS make them a preferred choice for protective coatings and lubricants, and they have been used for years in various manufacturing and industrial processes around the world. Although the use of PFAS has arguably improved many commercial products, they have been linked to adverse health outcomes such as developmental delays, liver damage, immune suppression, disruption of endocrine and reproductive systems, and some cancers. The current body of literature suggests that serum PFAS levels in dogs and cats are analogous to their human counterparts and that household pets experience similar changes in blood chemistry markers. The proximity of small children and household pets to PFAS-treated carpets and floors, in addition to their tendency to put things into their mouths, potentially allows pets to serve as sentinels for household PFAS exposure. To assess the suitability of pets as indicators for exposure, researchers need to understand the most likely sources of PFAS exposure for household pets and identify the biomarkers of biological effects in those animals. Understanding these parameters may alert veterinary clinicians to potential sources of contamination in the home and ultimately protect the lives of the children and animals who live there.

The variable associations between PFASs and biological aging by sex and reproductive stage in NHANES 1999–2018

BackgroundPer- and polyfluoroalkyl substances (PFASs) are endocrine disrupting chemicals that have myriad effects on human physiology. Estrogenic PFASs may influence biological aging by mimicking the activity of endogenous estrogens, which can decrease inflammation and oxidative stress and enhance telomerase activity. We hypothesized that PFAS exposure would be differentially associated with measures of biological aging based on biological sex and reproductive stage. MethodsWe analyzed associations between serum PFAS levels and measures of biological aging for pre- and postmenopausal women and men (n = 3193) using data from the 2003 to 2018 waves of the National Health and Nutrition Examination Survey. Examining PFASs both individually and in mixture models, we investigated four measures of clinical aging (Homeostatic Dysregulation, the Klemera-Doubal Method, Phenotypic Age Acceleration, and Allostatic Load), oxidative stress, and telomere length. ResultsPFOA and PFOS were negatively associated with Phenotypic Age Acceleration (e.g. decelerated aging) for men B = −0.22, 95% CI: −0.32, −0.12; B = −0.04, 95% CI: −0.06, −0.03) , premenopausal women (B = −0.58, 95% CI: −0.83, −0.32; B = −0.15, 95% CI: −0.20, −0.09), and postmenopausal women (B= −0.22, 95% CI: −0.43, −0.01; B = −0.05, 95% CI: −0.08, −0.02). In mixture models, we found net negative effects for Phenotypic Age Acceleration and Allostatic Load for men, premenopausal women, and postmenopausal women. We also found significant mixture effects for the antioxidants bilirubin and albumin among the three sample groups. We found no evidence to support effects on telomere length. DiscussionOur findings suggest that PFAS exposure may be inversely associated with some measures of biological aging at the relatively low levels of exposure in this sample, regardless of reproductive stage and sex, which does not support our hypothesis. This research provides insights into how PFAS exposure may variably influence aging measures depending on the physiological process investigated.

Occurrence of legacy and alternative per- and polyfluoroalkyl substances in serum from high exposure population and their disrupting effects on serum lipids and thyroid function

High exposure of per- and polyfluoroalkyl substances (PFAS) has been reported in main chemical production areas in China, while epidemiological study on exposure risk of PFAS is still limited. In this study, legacy and alternative PFAS were measured in serum samples from 161 adults living in Laizhou Bay, a famous chemical production area located in Shandong province, Northern China. Based on the concentrations of serum PFAS, the disrupting effects of PFAS on serum lipids and thyroid function were further explored. The results showed that the serum perfluorooctanoic acid (PFOA) (geometric mean (GM): 60 ng/mL) in this region was even higher than serum PFOA of residents living in PFOA contaminated water districts in United States and Sweden. 100 % of the serum PFOA was higher than the reference dose for increased total cholesterol (TC). Consistently, higher serum PFOA was marginally correlated with increased TC level (p = 0.062) and low-density lipoprotein (p = 0.065). In addition, higher perfluoroisopropyl perfluorooctanesulfonate and 6:2 chlorinated polyfluoroalkyl ether sulfonates (6,2 Cl-PFESA) were significantly correlated with increased high-density lipoprotein (p = 0.040, 0.022). No significant association was observed between individual PFAS and any thyroid function biomarker. However, using the principal component analysis derived factors to represent the co-exposure patterns, co-exposure of legacy long-chain PFAS showed synergistic effects on the free thyroxine, while the mixture of alternative PFAS showed a synergistic influence on the total and free triiodothyronine.

A prospective nested case-control study of serum concentrations of per- and polyfluoroalkyl substances and aggressive prostate cancer risk

Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent organic pollutants detectable in the serum of most U.S. adults. Some studies of highly-exposed individuals have suggested an association between PFAS and prostate cancer, but evidence from population-based studies is limited. We investigated the association between pre-diagnostic serum PFAS concentrations and aggressive prostate cancer risk in a large prospective study. We measured pre-diagnostic serum concentrations of eight PFAS, including perfluorooctanoate (PFOA), for 750 aggressive prostate cancer cases and 750 individually matched controls within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. We assessed the reproducibility of PFAS concentrations in serial samples collected up to six years apart among 60 controls using intraclass correlation coefficients (ICCs). Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association with prostate cancer, adjusting for other PFAS and potential confounders. Concentrations of most PFAS were consistent (ICC>0.7) across the serial samples over time. We observed an inverse association between PFOA and aggressive prostate cancer (ORcontinuous = 0.79, 95% CI = 0.63, 0.99), but the association was limited to cases diagnosed ≤3 years after blood collection and became statistically non-significant for cases diagnosed with later follow-up (>3 years, ORcontinuous = 0.90, 95% CI = 0.79, 1.03). Other PFAS were not associated with aggressive prostate cancer risk. Although we cannot rule out an increased risk at higher levels, our findings from a population with PFAS serum concentrations comparable to the general population do not support an association with increased risk of aggressive prostate cancer.

Correlation analysis between prenatal exposure of per-/polyfluoroalkyl compounds and neonatal outcome

Objective: To investigate the correlation between the prenatal exposure of per-/polyfluoroalkyl substances (PFASs) and the neonatal outcome. Methods: A total of 506 maternal infant cohort samples were collected in Hangzhou, Zhejiang province from 2020 to 2021. The exposure levels of seven PFASs in maternal serum before delivery were detected by solid-phase extraction-ultra performance liquid chromatography tandem mass spectrometry. Multivariable linear regression model was used to analyze the influence of prenatal exposure of PFASs on birth weight, birth length and Apgar score. Results: The maternal age, prenatal body mass index and gestation age were (31.3±4.3) years old, (26.7±3.2) kg/m2 and (265.0±28.3) days, respectively. The birth weight, birth length and scores of Apgar-1 and Apgar-5 were (3.1±0.8) kg, (49.3±2.9) cm, (9.88±0.47) points and (9.99±0.13) points, respectively. PFASs were widely distributed in maternal serum, with the highest concentration of (18.453±19.557) ng/ml, (6.756±9.379) ng/ml and (5.057±8.555) ng/ml for perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS) and 6∶2 chlorinated polyfluorinated ether sulfonate (Cl-PFESA), respectively. Maternal age, parity and delivery mode were associated with the exposure level of PFASs (P<0.05). Subgroup analysis showed that PFOS had negative effects on birth weight (β=-0.958), birth length (β=-0.073) and Apgar-5 score (β=-0.288) for neonates in the low birth weight (LBW) group. 6∶2 Cl-PFESA and 8∶2 Cl-PFESA inhibited the birth weight (β=-0.926; β=-0.552) and length (β=-0.074; β=-0.045) of newborn in the LBW group. In addition, 4∶2 fluorotelomer sulfonate (FTS) was associated with increased birth weight (β=0.111) and decreased Apgar-5 score (β=-0.030) in the normal weight group. Conclusion: Prenatal exposure to PFASs is associated with birth weight, birth length and Apgar-5 score. It is necessary to continue to pay attention to the impact of PFASs on fetal growth and development through maternal-fetal transmission.

Psychological distress in three Australian communities living with environmental per- and polyfluoroalkyl substances contamination

BackgroundEnvironmental chemical contamination is a recognised risk factor for psychological distress, but has been seldom studied in the context of per- and polyfluoroalkyl substances (PFAS) contamination. We examined psychological distress in a cross-sectional study of three Australian communities exposed to PFAS from the historical use of aqueous film-forming foam in firefighting activities, and three comparison communities without environmental contamination. MethodsParticipation was voluntary following recruitment from a PFAS blood-testing program (exposed) or random selection (comparison). Participants provided blood samples and completed a survey on their exposure history, sociodemographic characteristics, and four measures of psychological distress (Kessler-6, Distress Questionnaire-5, Patient Health Questionnaire-15, and Generalised Anxiety Disorder-7). We estimated prevalence ratios (PR) of clinically-significant psychological distress scores, and differences in mean scores: (1) between exposed and comparison communities; (2) per doubling in PFAS serum concentrations in exposed communities; (3) for factors that affect the perceived risk of living in a community exposed to PFAS; and (4) in relation to self-reported health concerns. ResultsWe recruited 881 adults in exposed communities and 801 in comparison communities. We observed higher levels of self-reported psychological distress in exposed communities than in comparison communities (e.g., Katherine compared to Alice Springs, Northern Territory: clinically-significant anxiety scores, adjusted PR = 2.82, 95 % CI 1.16–6.89). We found little evidence to suggest that psychological distress was associated with PFAS serum concentrations (e.g., Katherine, PFOS and anxiety, adjusted PR = 0.85, 95 % CI 0.65–1.10). Psychological distress was higher among exposed participants who were occupationally exposed to firefighting foam, used bore water on their properties, or were concerned about their health. ConclusionPsychological distress was substantially more prevalent in exposed communities than in comparison communities. Our findings suggest that the perception of risks to health, rather than PFAS exposure, contribute to psychological distress in communities with PFAS contamination.

Pregnancy-related hemodynamic biomarkers in relation to trimester-specific maternal per - and polyfluoroalkyl substances exposures and adverse birth outcomes

The fate of environmental chemicals in maternal and fetal tissues might be affected by pregnancy-related hemodynamic changes that occur across gestation. Specifically, hemodilution and renal function are hypothesized to confound associations between per- and polyfluoroalkyl substances (PFAS) exposure measures in late pregnancy with gestational length and fetal growth. We sought to analyze two pregnancy-related hemodynamic biomarkers, creatinine and estimated glomerular filtration rate (eGFR), as confounders of the trimester-specific relationships between maternal serum PFAS concentrations and adverse birth outcomes. Participants were enrolled in the Atlanta African American Maternal-Child Cohort between 2014 and 2020. Biospecimens were collected at up to two timepoints, which were categorized into the 1st trimester (N = 278; 11 mean weeks gestation), 2nd trimester (N = 162; 24 mean weeks gestation), and 3rd trimester (N = 110; 29 mean weeks gestation). We quantified six PFAS in serum, creatinine in serum and urine, and eGFR using the Cockroft-Gault equation. Multivariable regression models estimated the associations between single PFAS and their sum with gestational age at delivery (weeks), preterm birth (PTB, <37 gestational weeks), birthweight z-scores, and small for gestational age (SGA). Primary models were adjusted for sociodemographics. We additionally adjusted for serum creatinine, urinary creatinine, or eGFR in the confounding assessments. An interquartile range increase in perfluorooctanoic acid (PFOA) produced a non-significant reduction in birthweight z-score during the 1st and 2nd trimesters (β = −0.01 g [95% CI = −0.14, 0.12] and β = −0.07 g [95% CI = −0.19, 0.06], respectively) whereas the relationship was significant and positive during the 3rd trimester (β = 0.15 g; 95% CI = 0.01, 0.29). Trimester-specific effects were similar for the other PFAS and adverse birth outcomes, which persisted after adjusting for creatinine or eGFR.The relationships between prenatal PFAS exposure and adverse birth outcomes were not strongly confounded by renal function or hemodilution. However, 3rd trimester samples consistently exhibited different effects than those collected during the 1st and 2nd trimesters.

Prenatal Exposure to Legacy and Alternative Per- and Polyfluoroalkyl Substances and Neuropsychological Development Trajectories over the First 3 Years of Life.

The neurotoxic effects of prenatal exposure to per- and polyfluoroalkyl substances (PFAS) on offspring animals are well-documented. However, epidemiological evidence for legacy PFAS is inconclusive, and for alternative PFAS, it is little known. In this investigation, we selected 718 mother-child pairs from the Chinese Maoming Birth Cohort Study and measured 17 legacy and alternative PFAS in the third-trimester serum. Neuropsychological developments (communication, gross motor function, fine motor function, problem solving ability, and personal-social skills) were assessed at 3, 6, 12, 18, 24, and 36 months using the Ages and Stages Questionnaires 3rd edition. Trajectories of each subscale were classified into persistently low and persistently high groups via group-based trajectory modeling. Logistic regression and grouped weighted quantile sum were fitted to assess the potential effects of individual PFAS and their mixtures, respectively. Higher linear PFHxS levels were associated with elevated odds for the persistently low trajectories of communication (OR = 1.73; 95% CI: 1.12, 2.66) and problem solving ability (OR = 2.11; 95% CI: 1.14, 3.90). Similar findings were observed for linear PFOS, 1m-PFOS, PFDA, PFDoDA, PFUnDA, and legacy PFAS mixture. However, no association was observed for alternative PFAS and their mixture. We provided insights into the longitudinal links between prenatal legacy/alternative PFAS exposure and neuropsychological development trajectories over the first 3 years of life.

Association of per- and polyfluoroalkyl substance exposure with fatty liver disease risk in US adults

Per- and polyfluoroalkyl substances (PFAS) are widespread pollutants with demonstrated hepatotoxicity. Few studies have examined the association between PFAS and fatty liver disease (FLD) risk in an adult population. In this cross-sectional study of participants from the 2017-2018 National Health and Nutrition Examination Survey, serum PFAS were measured, and FLD cases were ascertained by vibration-controlled transient elastography. Logistic regression models were used to examine the association between circulating PFAS levels and FLD risk. Analyses were stratified into non-alcoholic FLD and alcoholic FLD risk groups by alcohol intake status, as well as controlling for other risk factors, including personal demographics, lifestyle factors, and related health factors. Among 1,135 eligible participants, 446 had FLD. For FLD risk, the multivariable-adjusted odds ratio per log-transformed SD increase (ORSD) in perfluorohexane sulfonate (PFHxS) was 1.13 (95% CI 1.01-1.26). The association between PFHxS and FLD appeared stronger among individuals with obesity or high-fat diets (both p interaction <0.05). When limiting the analysis to 212 heavy drinkers (≥2 drinks/day for women and ≥3 drinks/day for men), significantly higher risk of alcoholic FLD was found for higher levels of perfluorooctanoic acid (ORSD 1.79; 95% CI 1.07-2.99), PFHxS (ORSD 2.06; 95% CI 1.17-3.65), and perfluoroheptane sulfonic acid (ORSD 1.44; 95% CI 1.00-2.07), and marginally significant higher risk for total PFAS (ORSD 2.12; 95% CI 0.99-4.54). In never or light drinkers, we did not observe any significant association between PFAS and non-alcoholic FLD. Significant positive associations were found for PFAS with aspartate aminotransferase, gamma-glutamyl transaminase, total bilirubin, and albumin (β ranged from 0.008 to 0.101, all p <0.05). Higher serum PFAS was moderately associated with FLD risk and worse liver function in the general population, and among those with independent risk factors, including heavy alcohol intake, obesity, or high-fat diets, PFAS increased the risk. These results suggest synergistic effects on hepatic steatosis between PFAS exposures as measured through biomonitoring data and lifestyle risk factors in a nationally representative US population. The per- and polyfluoroalkyl substances (PFAS) may convey higher risk for chronic liver disease in humans. Among 1,135 US adults in the 2017-2018 National Health and Nutrition Examination Survey, we found that higher serum PFAS was associated with higher fatty liver disease risk and worse liver function, especially among those with liver disease risk factors, including heavy alcohol intake, obesity, or high-fat diets. Continuously monitoring PFAS in the population and examining how they potentiate risk to the liver are essential.

Longitudinal measurements of per- and poly-fluoroalkyl substances (PFAS) in archived human serum samples between 1975 and 1995 in Australia.

Per- and poly-fluoroalkyl substances (PFAS) are a group of manmade compounds produced since the 1950s and used in a range of industrial processes and consumer products. In Australia, PFAS serum concentrations have been measured in the general population since 2002. However, few studies have retrospectively measured PFAS concentrations in serum samples representative of a general population prior to 2000, none of which have been conducted in Australia. To understand the general population's exposure to PFAS prior to 2002, longitudinal PFAS serum concentration measurements are required. In the current study, we accessed 'The Busselton Health Study Data Bank' to analyse archived serum samples for PFAS. Repeat serum samples collected in 1975, 1981 and 1995 were obtained from 17 participants. Of the 35 PFAS analysed, 13 PFAS were detected in the serum samples collected in 1975. Both the detection frequency and ∑PFAS serum concentrations increased between 1975 and 1995. Median ∑PFAS serum concentration increased over 7-fold; from 3.3ng/mL in 1975-26ng/mL in 1995. The increase in serum concentrations reflects the global production history of these PFAS during this period in time.

Red Blood Cell Folate Modifies the Association between Serum Per- and Polyfluoroalkyl Substances and Antibody Concentrations in U.S. Adolescents.

Per- and polyfluoroalkyl substances (PFAS) exposure has been associated with reduced antibody levels. Higher red blood cell (RBC) folate was previously associated with lower serum PFAS concentrations in adolescents. This study included 819 adolescents aged 12-19 years who had detectable rubella and measles antibody levels in serum from the U.S. National Health and Nutrition Examination Survey 2003-2004 and 2009-2010 cycles. We found inverse associations between serum PFOS and PFHxS and rubella antibodies, between PFOA and mumps antibodies, and between PFAS mixtures and rubella and mumps antibodies, only among adolescents with RBC folate concentrations <66th percentile (lower folate group) while not among adolescents with higher RBC folate levels (upper folate group). Specifically, per quartile increase in serum concentrations of the total PFAS mixture was associated with a 9.84% (95% CI: -15.57%, -3.74%) decrease in rubella antibody and an 8.79% (95% CI: -14.39%, -2.82%) decrease in the mumps antibody concentrations only in the lower folate group, while null associations were found for the upper folate group. If confirmed in mechanistic studies or prospective epidemiologic studies, these findings may have important implications for using folate as a mitigation measure against immune-related PFAS effects.

Systematic review and meta-analysis of epidemiologic data on vaccine response in relation to exposure to five principal perfluoroalkyl substances

BackgroundEpidemiologic studies of serum per- and polyfluoroalkyl substances (PFAS) and antibody response to vaccines have suggested an adverse association, but the consistency and magnitude of this association remain unclear. ObjectiveThe goal of this systematic review was to determine the size of the association between a doubling in perfluoroalkyl substances (PFAS) serum concentration and difference in loge antibody concentration following a vaccine, with a focus on five PFAS: perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA). Data sourceWe conducted online searches of PubMed and Web of Science through May 17, 2022 and identified 14 eligible reports published from 2012 to 2022. Study eligibility criteria, participants, and interventionsWe included studies conducted in humans, including mother–child pairs, which examined serum PFAS concentration in relation to serum concentration of antibody to a specific antigen following a vaccine.Study appraisal and synthesis methods: We used the risk of bias assessment for non-randomized studies of exposure and certainty assessment method proposed by Morgan et al. (2019). Using a multilevel meta-regression model, we quantitatively synthesized the data. ResultsThe 14 reports represented 13 unique groups of subjects; the frequency of studies of a given antibody was Tetanus (n = 7); followed by Diphtheria (6); Measles (4); Rubella (3); Haemophilus influenzae type b and Influenza A H1N1 (2 each); and Hepatitis A, Hepatitis B, Influenza A H2N3, Influenza B, and Mumps (1 each). There were approximately 4,830 unique participants included in the analyses across the 14 reports. The models of coefficients between antibody concentration and the five principal PFAS showed homogeneity of associations across antibody types for each principal PFAS. In the models with all antibodies treated as one type, evidence of effect modification by life stage was present for PFOA and PFOS, and for consistency, all associations were evaluated for all ages and for children. The summary associations (coefficients for difference in loge[antibody concentration] per doubling of serum PFAS) with 95% confidence intervals that excluded zero (“statistical support”), and certainty of evidence ratings were as follows: for PFOA and all antibodies treated as one type in all ages, −0.06 (-0.10, −0.01; moderate) and in children, −0.10 (-0.16, −0.03; moderate); for Diphtheria in children, −0.12 (-0.23, −0.00; high); for Rubella in all ages, −0.09 (-0.17, −0.01; moderate), and for Tetanus in children, −0.12 (-0.24, −0.00; moderate). For PFOS the summary associations were, for all antibodies treated as one type in all ages, −0.06 (-0.11, −0.01; moderate) and in children, −0.10 (-0.18, −0.03; moderate); for Rubella in all ages, −0.09 (-0.15, −0.03; high) and in children, −0.12 (-0.20, −0.04; high). For PFHxS the summary associations were, for all antibodies treated as one type in all ages, −0.03 (-0.06, −0.00; moderate) and in children, −0.05 (-0.09, −0.00; low); and for Rubella in children, −0.07 (-0.11, −0.02; high). Summary associations for PFNA and PFDA did not have statistical support, but all PFAS studied tended to have an inverse association with antibody concentrations. Limitations and conclusionsEpidemiologic data on immunosuppression and five principal PFAS suggest an association, with support across antibodies against multiple types of antigens. Data on Diphtheria, Rubella, and Tetanus were more supportive of an association than for other antibodies, and support was greater for associations with PFOA, PFOS, and PFHxS, than for PFNA or PFDA. The data on any specific antibody were scarce. Confounding factors that might account for the relation were not identified. Nearly all studies evaluated were judged to have a low or moderate risk of bias.