Serum Perfluoroalkyl Substances Concentrations Research Articles

A randomized controlled trial of a housing intervention to reduce endocrine disrupting chemical exposures in children

Few studies have considered household interventions for reducing endocrine disrupting chemical (EDC) exposures. We conducted a secondary analysis of a randomized controlled trial, originally designed to reduce lead exposure, to evaluate if the intervention lowered EDC exposures in young children. Study participants were children from the Cincinnati, Ohio area (n = 250, HOME Study). Prenatally, families received a housing intervention that included paint stabilization and dust mitigation, or as a control, injury prevention measures. At 24-months, we measured organophosphate esters (OPEs) and phthalates or their metabolites in dust and urine. We measured perfluoroalkyl substances (PFAS) in dust and serum at 24- and 36-months, respectively. We assessed associations between dust and biomarker EDCs using Spearman correlations, characterized EDC mixtures via principal components analysis, and investigated treatment effects using linear regression. To mitigate selection bias, we fit statistical models using inverse probability of retention weights. Correlations between dust EDCs and analogous biomarkers were weak-to-moderate (ρ’s ≤ 0.3). The intervention was associated with 23 % (95 % CI: −38, −3) lower urinary DEHP metabolites and, in a per-protocol analysis, 34 % lower (95 % CI: −55, −2) urinary MBZP. Additionally, among Black or African American children, the intervention was associated with lower serum concentrations of several PFAS (e.g., −42 %; 95 % CI: −63, −8 for PFNA). Household interventions that include paint stabilization and dust mitigation may reduce childhood exposures to some phthalates and PFAS in Blacks/African Americans. These findings highlight the need for larger studies with tailored and sustained housing interventions.

Association between serum perfluoroalkyl substances concentrations and non-alcoholic fatty liver disease among Korean adults: a cross-sectional study using the National Environmental Health Survey cycle 4.

Perfluoroalkyl substances (PFAS) are widely used in industry and daily life due to their useful properties. They have a long half-life, accumulate in the body, and there is evidence that they are associated with biomarkers of lipid metabolism and liver damage. This may suggest non-alcoholic fatty liver disease (NAFLD) caused by PFAS. However, since there has been no study analyzing the relationship between PFAS and NAFLD in the entire population in Korea. We sought to confirm the relationship between serum PFAS concentration and NAFLD prevalence in Korean adults using the Korean National Environmental Health Survey (KoNEHS) cycle 4. The study was conducted on 2,529 subjects in 2018-2019 among KoNEHS participants. For the diagnosis of NAFLD, the hepatic steatosis index (HSI) was used, and the geometric mean and concentration distribution of serum PFAS were presented. Logistic regression was performed to confirm the increase in the risk of NAFLD due to changes in PFAS concentration, and the odds ratio and 95% confidence interval (CI) were calculated. In both adjusted and unadjusted models, an increased odds ratio was observed with increasing serum concentrations of total PFAS and perfluorooctane sulfonate (PFOS) in the non-obese group. In the adjusted model, the odds ratios for serum total PFAS and PFOS were 6.401 (95% CI: 1.883-21.758) and 7.018 (95% CI: 2.688-18.319). In this study, a higher risk of NAFLD based on HSI was associated with serum total PFAS, PFOS in non-obese group. Further research based on radiological or histological evidence for NAFLD diagnosis and long-term prospective studies are necessary. Accordingly, it is necessary to find ways to reduce exposure to PFAS in industry and daily life.

Higher serum concentrations of PFAS among pesticide exposed female greenhouse workers

BackgroundLong-chained poly- and perfluoroalkyl substances (PFAS) have been used in pesticide formulations but their potential impact on human PFAS exposure has not been addressed. ObjectivesTo investigate if occupationally pesticide exposed female greenhouse workers in Denmark had higher serum concentrations of PFAS than a comparable background population. MethodsSerum samples collected between 1996 and 2001 from 181 pregnant greenhouse workers and a contemporary urban population of 48 pregnant women were analyzed for eight PFAS: perfluorooctane sulfonate (PFOS), perfluorohexane sulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluorooctane sulfonamide (FOSA), N-methyl perfluorooctane sulfonamido acetic acid (N-MeFOSAA), and N-ethyl perfluorooctane sulfonamido acetic acid (N-EtFOSAA). ResultsThe concentrations of PFOA, PFOS, and the PFOS precursors N-MeFOSAA, N-EtFOSAA, and FOSA were higher, and PFHxS was lower, among greenhouse workers than the comparison population. After adjusting for age and parity, serum concentrations of N-MeFOSAA, N-EtFOSAA, and FOSA were 2-to-3-fold higher, and the major PFAS in serum, PFOS and PFOA, were 30–50 % higher among the greenhouse workers. ConclusionHigher serum concentrations of some legacy PFAS among female greenhouse workers indicate that exposure to pesticides is a potential pathway of exposure. Although PFAS use in pesticide applications may appear to be a minor source of exposure for the general population, this pathway deserves attention in risk assessment.

Associations between perfluoroalkyl substances and the severity of non-alcoholic fatty liver disease

BackgroundNon-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease worldwide and the determinants driving its severity remain to be elucidated. Perfluoroalkyl substances (PFAS) are synthetic chemical compounds. They are used in commonplace products and persistent in water, soil and the human body. In vitro and animal studies suggest a pathogenic role for PFAS in metabolic diseases such as NAFLD. ObjectivesWe aimed to evaluate the association between NAFLD severity and serum PFAS concentrations in humans. MethodsOne hundred biopsy-proven NAFLD patients were included with a well-balanced distribution between the different stages of severity: 25 patients with simple steatosis, 25 with early non-alcoholic steatohepatitis (NASH and F0–F1 fibrosis), 33 with fibrotic NASH (NASH and F2–F3 fibrosis), and 17 with cirrhotic NASH (NASH and F4 fibrosis). Liver histological features were evaluated according to the NASH Clinical Research Network classification. Seventeen PFAS were measured by high-performance liquid chromatography coupled with tandem mass spectrometry on serum samples stored at −80 °C. ResultsThe median age was 60 years, 61 % of patients were male, 46 % had diabetes and the median body mass index (BMI) was 32 kg/m2. Long-chain PFAS were associated with steatosis grade (p = 0.03). Among the nine PFAS detected in > 50 % of the patients, Perfluoro-n-heptanoic acid (PFHpA) showed significantly higher concentrations in grade 3 steatosis versus grade 1 (p = 0.02). Perfluoro-n-dodecanoic acid (PFDoA) concentrations were higher in patients with significant fibrosis (p = 0.04) and PFHpA in patients with advanced fibrosis (p = 0.02). The association between PFHpA and steatosis grade remained significant in multivariate analysis adjusted for age, gender, BMI, diabetes presence and dyslipidemia (p = 0.004). DiscussionOur study showed a significant association between PFHpA and liver steatosis in NAFLD. According to data available in the literature, PFHpA could be implicated in liver steatosis through β-oxidation and biosynthesis of fatty acids.

Perfluoroalkyl substances (PFAS) and lead (Pb) as “cardiovascular disruptors” in 9–11-year-old children living in Syracuse, New York, United States

ObjectivePer- and polyfluoro–alkyl substances (PFAS) and lead (Pb) are ubiquitous environmental toxicants with apparent impact on cardiovascular disease (CVD) risk. As one possible mechanism for this increased risk, we have previously demonstrated an association between Pb exposure and heightened cardiovascular reactivity to acute psychological stress, a CVD risk factor. The present study expands this approach and considers both PFAS and Pb exposures (and the possible interaction). MethodsWe assessed 14 serum PFAS and whole blood Pb concentrations in a sample of 9–11 year-old children (N = 291; 43.2% White, 56.8% Black; 53.5% female). We measured cardiovascular functioning at rest and during psychological stress as well as multiple indicators of subclinical CVD including resting blood pressure (BP), carotid-femoral pulse wave velocity (cfPWV), carotid intima-media thickness (cIMT), and left ventricular mass (LVM). Data analysis included general linear modeling as well as a non-parametric approach to study metal mixtures, specifically Bayesian Kernel Machine Regression (BKMR). ResultsSignificant interactions between different PFAS and with Pb suggest the importance of considering toxicant mixtures when assessing potential disruption of the cardiovascular system. The pattern of findings suggests that greater “vascular reactivity” (elevated BP and vascular resistance during acute psychological stress) was associated with higher concentrations of perfluorononanoic acid (PFNA), perfluorohexane sulfonate (PFHxS), and Pb, but only when perfluorooctanoic acid (PFOA) was concurrently elevated. With respect to subclinical outcomes, increasing perfluorodecanoic acid (PFDA) was associated with greater cIMT (β = 0.21, p = 0.010). ConclusionTo our knowledge this is the first study to consider how PFAS exposures might affect cardiovascular functioning and subclinical disease. Although a complex pattern of associations emerged, it does appear that PFAS and Pb can be classified as “cardiovascular disruptors” in children. Further research is needed to replicate these novel findings and determine whether these disruptions produce future cardiovascular disease.

Decreased levels of perfluoroalkyl substances in patients receiving hemodialysis treatment

Perfluoroalkyl substances (PFAS) have been reported to be harmful to multiple organs in the human body. Based on a previous study suggesting that hemodialysis (HD) may be a means of eliminating PFAS from the human body, we aimed to compare the serum PFAS concentrations of patients undergoing regular HD, patients with chronic kidney disease (CKD) and controls. Additionally, we also investigated the correlation between PFAS and biochemical data, as well as concurrent comorbidities. We recruited 301 participants who had been on maintenance dialysis for >90 days, 20 participants with stage 5 non-dialysis CKD, and 55 control participants who did not have a diagnosis of kidney disease, with a mean creatinine level of 0.77 mg/dl. Eight different PFAS, namely perfluorooctanoic acid (PFOA), total and linear perfluorooctanesulfonic acid (PFOS), perfluoroheptanoic acid (PFHpA), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA), were measured using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Spearman correlation and multivariable linear regression with 5 % false discovery rate were used to evaluate the relationships between PFAS and clinical parameters in HD patients and controls. Circulating concentrations of seven PFAS, including total and linear PFOS (T-PFOS and L-PFOS) PFDA, PFNA, PFHxS, PFOA, and PFUnDA, were significantly lower in the HD group compared to the CKD and control group. For the interplay between biochemical data and PFAS, all of the studied PFAS were positively correlated with aspartate aminotransferase, alanine aminotransferase, glucose, blood urea nitrogen, ferritin, and vitamin D in the controls, while in HD patients, the PFAS were all positively correlated with albumin, uric acid, iron, and vitamin D. These findings may offer valuable insights for future studies seeking to eliminate PFAS.

Serum Concentrations of Selected Poly- and Perfluoroalkyl Substances (PFASs) in Pregnant Women and Associations with Birth Outcomes. A Cross-Sectional Study from Southern Malawi.

Pervasive exposure to per-and polyfluoroalkyl substances (PFASs) shows associations with adverse pregnancy outcomes. The aim of the present study was to examine the determinants of different serum PFAS concentrations in late pregnancy and their relationship with birth outcomes in southern Malawi. The sample included 605 pregnant women with a mean age of 24.8 years and their offspring from three districts in the southern region of Malawi. Six PFAS were measured in serum from third-trimester women. The serum PFAS concentrations were assessed with head circumference, birth length, birth weight, gestational age and ponderal index. Participants living in urban areas had significantly higher serum levels of PFOA, PFNA and SumPFOS, while SumPFHxS concentrations were higher in women from rural settings. High PFOA, PFNA and SumPFHxS concentrations were generally inversely associated with head circumference. Birth length was negatively associated with PFOA and PFNA while SumPFHxS was negatively associated with birth weight. SumPFOS was inversely associated with gestational age. Urban area of residence was the strongest predictor for high PFAS concentrations in the maternal serum and was generally associated with adverse birth outcomes. The results highlight the need to investigate SumPFHxS further as it follows a pattern that is different to similar compounds and cohorts.

Prenatal perfluoroalkyl substances exposure and neurodevelopment in toddlers: Findings from SMBCS

BackgroundPrenatal perfluoroalkyl substances (PFAS) exposure has been reported to affect offspring neurodevelopment, while epidemiological evidences were limited and inconsistent. ObjectivesWe aimed to evaluate the associations between cord serum PFAS concentrations and neurodevelopment in toddlers from 1 to 3 years of age. MethodsA total of 716 children from Sheyang Mini Birth Cohort Study (SMBCS) were included in this study. 12 PFAS concentrations were quantified in cord serum. Neurodevelopment was assessed using the Developmental Screen Test for Children Aged 0–6 Years at 1 year and the Gesell Developmental Schedules (GDS) at 2 and 3 years, respectively. Development quotient (DQ) z-score was standardized from DQ to eliminate the difference caused by two methods. We used generalized linear model (GLM) and Bayesian kernel machine regression (BKMR) to explore the associations of single or mixture PFAS exposure with neurodevelopment measurements at each time point. Associations between PFAS exposure and longitudinal changes in DQ z-score were investigated through generalized estimating equation (GEE) and trajectory analysis. ResultsIn general, prenatal PFAS concentrations showed negative associations with neurodevelopment measurements at specific age. When accounting for longitudinal changes from 1 to 3 years of age, PFOA was negatively associated with DQ z-score (β = −0.212, 95% CI: −0.422, −0.003), the association was only found significant in boys after stratified by gender (β = −0.327, 95% CI: −0.616, −0.038). Meanwhile, increased PFBS (OR = 2.159, 95% CI: 1.177, 3.959) and PFHpA (OR = 1.700, 95% CI: 1.016, 2.846) exposure was associated with elevated odds for the low-score trajectory group. The results of mixture of PFAS further confirmed above findings. ConclusionsOur findings suggested that prenatal PFAS exposure may be associated with adverse neurodevelopment effects in the first 3 years of life. Further studies are warranted to confirm our findings.

Human serum poly- and perfluoroalkyl substance concentrations and their associations with gestational diabetes mellitus

Poly- and perfluoroalkyl substances (PFAS), which have been found in high concentrations in maternal serum, have the potential to impair glucose metabolism in pregnant women. However, the effects of PFAS exposure on the risk of gestational diabetes mellitus (GDM) remain inconsistent. In the current investigation, a case-control study involving 135 patients with GDM and 69 controls was conducted in Hangzhou, China. We determined the concentrations of 17 PFAS in maternal serum from each participant and elucidated the associations between those concentrations and the risk of GDM. Among the 17 PFAS, perfluorooctanesulfonate (median 7.53 and 7.44 ng/mL) was the predominant PFAS in both cases and controls, followed by perfluorooctanoic acid (PFOA; median 5.22 and 5.03 ng/mL) and 6:2 chlorinated perfluoroalkyl ether sulfonate (6:2 Cl-PFESA; median 2.58 and 2.42 ng/mL). Conditional logistic regression analysis showed that the maternal serum continuous levels of PFOA, perfluorononanoic acid (PFNA), perfluorohexanesulfonate (PFHxS), and 6:2 Cl-PFESA were significantly associated with the GDM risk, with adjusted odds ratios (ORs) of 1.84 (95% confidence interval (CI): 1.26, 3.51), 1.47 (1.17, 3.29), 1.33 (1.72, 3.48), and 1.34 (1.17, 2.53), respectively. In the adjusted model, the ORs of GDM for increasing tertiles of PFOA, PFNA, PFHxS, and 6:2 Cl-PFESA significantly increased. The adjusted ORs (95% CI) were 3.38 (2.16, 6.89), 2.61 (1.26, 5.40), 3.46 (1.64, 6.30), and 3.50 (1.62, 6.91) at the highest concentrations of PFOA, PFNA, PFHxS, and 6:2 Cl-PFESA, respectively. These results suggest that higher PFAS exposure, reflected in serum PFAS concentrations, was associated with GDM incidence in pregnant women.

Bayesian Estimation of Human Population Toxicokinetics of PFOA, PFOS, PFHxS, and PFNA from Studies of Contaminated Drinking Water.

Setting health-protective standards for poly- and perfluoroalkyl substances (PFAS) exposure requires estimates of their population toxicokinetics, but existing studies have reported widely varying PFAS half-lives (T½) and volumes of distribution (Vd). We combined data from multiple studies to develop harmonized estimates of T½ and Vd, along with their interindividual variability, for four PFAS commonly found in drinking water: perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonate (PFHxS). We identified published data on PFAS concentrations in human serum with corresponding drinking water measurements, separated into training and testing data sets. We fit training data sets to a one-compartment model incorporating interindividual variability, time-dependent drinking water concentrations, and background exposures. Use of a hierarchical Bayesian approach allowed us to incorporate informative priors at the population level, as well as at the study level. We compared posterior predictions to testing data sets to evaluate model performance. Posterior median (95% CI) estimates of T½ (in years) for the population geometric mean were 3.14 (2.69, 3.73) for PFOA, 3.36 (2.52, 4.42) for PFOS, 2.35 (1.65, 3.16) for PFNA, and 8.30 (5.38, 13.5) for PFHxS, all of which were within the range of previously published values. The extensive individual-level data for PFOA allowed accurate estimation of population variability, with a population geometric standard deviation of 1.57 (95% CI: 1.42, 1.73); data from other PFAS were also consistent with this degree of population variability. Vd estimates ranged from 0.19 to across the four PFAS, which tended to be slightly higher than previously published estimates. These results have direct application in both risk assessment (quantitative interspecies extrapolation and uncertainty factors for interindividual variability) and risk communication (interpretation of monitoring data). In addition, this study provides a rigorous methodology for further refinement with additional data, as well as application to other PFAS. https://doi.org/10.1289/EHP10103.

Association between serum concentrations of perfluoroalkyl substances and global DNA methylation levels in peripheral blood leukocytes of Japanese women: A cross-sectional study

Global DNA methylation levels in peripheral blood leukocytes can be a biomarker for cancer risk; however, levels can be changed by various factors such as environmental pollutants. We investigated the association between serum concentrations of perfluoroalkyl substances (PFASs) and global DNA methylation levels of leukocytes in a cross-sectional study using the control group of a Japanese breast cancer case-control study [397 women with a mean age of 54.1 (SD 10.1) years]. Importantly, our analysis distinguished branched PFAS isomers as different from linear isomers. The serum concentrations of 20 PFASs were measured by in-port arylation gas-chromatography negative chemical ionization mass spectrometry. Global DNA methylation levels in peripheral blood leukocytes were measured using a luminometric methylation assay. Associations between log10-transformed serum PFAS concentrations and global DNA methylation levels were evaluated by regression coefficients in multivariable robust linear regression analyses. Serum concentrations of 13 PFASs were significantly associated with increased global DNA methylation levels in leukocytes. Global DNA methylation was significantly increased by 1.45 %–3.96 % per log10-unit increase of serum PFAS concentration. Our results indicate that exposure to PFASs may increase global DNA methylation levels in peripheral blood leukocytes of Japanese women.

Association of perfluoroalkyl substances (PFAS) with lipid trajectories in midlife women: the Study of Women's Health Across the Nation

BACKGROUND AND AIM: Despite lipid-lowering effects of perfluoroalkyl substances (PFAS) observed in rodent models, PFAS have been associated with unfavorable blood lipid profiles in human populations. However, evidence from longitudinal studies in the general population is limited. We examined the association of serum concentrations of PFAS with longitudinal trajectories of blood lipids in the Study of Women's Health Across the Nation. METHODS: We included 1143 women aged 45-56 years in 1999-2000. Concentrations of PFAS including linear and branched perfluorooctane sulfonic acid (n-PFOS and Sm-PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS) were measured in serum collected at baseline. Total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol, and triglycerides were measured in blood annually or biannually during follow-up through 2016. Using latent class growth models (LCGMs), trajectories of each lipid were estimated based on the population data. The associations between PFAS and lipid trajectory classes were evaluated by multinomial log-linear models with latent class membership as outcomes and log-transformed PFAS as exposure. RESULTS: Three distinct lipid trajectories (low, medium, and high trajectories) were identified. After adjustment for covariates, n-PFOS and Sm-PFOS were positively associated with higher LDL cholesterol [ORs (95% CI) for high vs. low trajectory per doubling of each PFAS: 1.28 (1.04, 1.56) and 1.24 (1.04, 1.48), respectively]. N-PFOS, n-PFOA, PFNA, and PFHxS were inversely associated with higher triglycerides [ORs (95% CIs) for high vs. low trajectory per doubling of each PFAS: 0.72 (0.55, 0.94), 0.65 (0.50, 0.84), 0.78 (0.62, 1.00), and 0.76 (0.62, 0.93), respectively]. The associations of PFAS with total or HDL cholesterol were insignificant. CONCLUSIONS: Higher serum concentrations of selected PFAS were associated with a higher trajectory of LDL cholesterol and a lower trajectory of triglycerides. Further studies on the underlying mechanisms of the findings are warranted. KEYWORDS: PFAS, dyslipidemia, midlife women

Lipoprotein profiles associated with exposure to poly- and perfluoroalkyl substances (PFASs) in the EuroMix human biomonitoring study

Exposure to per- and polyfluoroalkyl substances (PFASs) is associated with increased blood cholesterol. Although elevated cholesterol is a well-established risk factor for cardiovascular diseases (CVD), it is not clear whether PFASs affect this risk. Lipoprotein subclasses are emerging biomarkers for disease risk and lipoprotein profiling may provide an insight to physiological implications of PFAS exposure. We explored the association between serum PFAS concentrations and lipoprotein subclasses in a cross-sectional study. We determined the concentrations and lipid composition of the major subclasses of lipoproteins in plasma samples from 127 adult participants of the EuroMix human biomonitoring study by nuclear magnetic resonance (NMR). Serum concentrations of 17 PFASs showed a detection frequency between 30 and 100% and were included in further analyses. We examined the associations between PFAS concentrations and lipoprotein subclasses by linear mixed-effect regression models, adjusted for confounders. In the adjusted models, positive associations were found between several PFASs and cholesterol concentrations in large to medium sized HDL and medium sized LDL particles. We found a 4–12% increase in HDL cholesterol per interquartile range (IQR) increase for several PFASs. In women the associations with PFNA, PFUnDA, PFDoDA and PFOS were significant after adjustment for multiple comparisons. Similar magnitude of change was observed between longer chained PFASs and LDL cholesterol, and a few of these associations reached significance for cholesterol in large to medium LDL particle sizes in women. No significant associations with plasma triglycerides were observed. However, most PFASs tended to be associated with reduction in VLDL (very low-density lipoproteins) particle number and VLDL triglyceride. Findings from this exploratory study, suggest that background PFAS exposures influence particle size distributions and lipid composition of plasma lipoprotein subclasses, and that these effects may be more prominent in women. A two-points lipoprofiling for all subjects indicated both low intra-individual variability and good analytical reproducibility.

Mothers living with contamination of perfluoroalkyl substances: an assessment of the perceived health risk and self-reported diseases.

Widespread contamination of the superficial, drinking, and groundwater by perfluoroalkyl substances (PFASs) was discovered in the Veneto Region (northeast of Italy) in 2013. Mothers from the contaminated area were concerned about the effects of PFAS on their own and their children's health. We determined the factors that influenced the perceived risk of PFAS and the presence of self-reported diseases by conducting a study with 384 mothers of children aged 1-13years living in the contaminated area (Red Zone, Veneto, Italy). Information on demography, the sources of exposure, and the health condition of the mothers was collected through an online survey. The serum PFAS concentration was recorded for some of the participants. We determined the factors influencing the perceived risk, risk of health outcomes, and serum PFAS levels through regression analyses. The PFAS perceived risk of the mothers increased with an increase in the trust in scientific institutions and social media, and when many friends were present, trust in politics and full-time employment had a protective effect. The PFAS perceived risk increased the occurrences of self-reported and autoimmune diseases. Longer residence (> 20years) in the most exposed area (Red Zone A) increased the frequency of some health outcomes. Serum PFAS concentrations decreased with breastfeeding, but increased with tap water consumption, residence in Red Zone A, and residence time. The PFAS perceived risk of the mothers was associated with many factors that influenced reporting of health issues. The association between PFAS exposure and health outcomes needs further investigation.

Umbilical cord serum concentrations of perfluorooctane sulfonate, perfluorooctanoic acid, and the body mass index changes from birth to 5 1/2\xa0years of age

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

No association between maternal and child PFAS concentrations and repeated measures of ADHD symptoms at age 2½ and 5 years in children from the Odense Child Cohort

IntroductionThe potential impact of exposure to perfluoroalkyl substances (PFAS) on childhood Attention-Deficit Hyperactivity-Disorder (ADHD) is unclear and deserves scrutiny. The majority of previously conducted longitudinal studies found no association between maternal serum-PFAS concentrations and ADHD symptoms in the offspring, but some studies observed possible associations with postnatal PFAS exposures, mainly in girls. ObjectiveTo investigate the association between maternal and child serum concentrations of five PFAS and symptoms of ADHD at ages 2½ and 5 years. MethodsIn the Odense Child Cohort (OCC) women were recruited in early pregnancy in 2010–12 and their children are being prospectively followed. Mothers donated serum samples in the first trimester and children at age 18 months to be analyzed for perfluorohexane sulfonic acid (PFHxS), perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA). Parents completed the Child Behavior Check List for ages 1.5–5 years (CBCL/1½-5), including a 6-item ADHD symptom scale at age 2½ years and again at 5 years. Negative binomial and logistic regression models taking account of repeated measures were used to investigate the association between maternal and child serum-PFAS concentrations and the ADHD symptom score. Effect modification by child sex was investigated as well. ResultsA total of 1138 mother-child pairs were included. At age 2½ years, 17.4% of the children had an ADHD scale score ≥ 5 (equivalent to the 90th percentile), whereas the proportion was 15.8% at age 5. We found no association between either maternal or child PFAS concentrations in serum and symptoms of ADHD at age 2½ or 5 years, and no evidence of effect modification by sex. ConclusionWe found no evidence of an association between early-life PFAS exposure and the risk of developing symptoms of ADHD.

Poly- and perfluoroalkyl substances (PFASs) and lipidomics and inflammatory proteomics in the human EuroMix study

BACKGROUND AND AIM: Exposure to PFASs has been associated with high cholesterol levels, lower vaccination response and higher childhood infections, in epidemiological studies. The mechanistic pathways involved are often unknown. Biomarkers of effect can provide insight in the biological implications of PFAS exposure. We explored the association between serum PFAS concentrations, lipoprotein particle subclasses and inflammatory biomarkers. METHODS: In 127 adult participants of the EuroMix human biomonitoring study (mean age: 40 years, 70% women) we determined the concentrations and lipid content of the major lipoproteins in two plasma samples by nuclear magnetic resonance and the serum concentrations of five perfluoroalkyl sulfonates (PFSAs) and six perfluoroalkyl carboxylates (PFCAs), and analysed their association by linear mixed-effect regression models. Further, we used an OLINK high-throughput proteomic assay to analyze plasma inflammatory proteins and explored the association with PFAS by linear regression analysis. RESULTS:Most PFCAs, and PFOS were positively associated with HDL and LDL cholesterol concentrations and negatively associated with VLDL cholesterol and triglyceride concentrations in all lipoproteins. One interquartile range (IQR) increase in PFNA, PFDoDA and PFOS was associated with 11%-12% higher HDL cholesterol, independent of HDL particle size. One IQR increase in PFTrDA, PFHpS and PFOS was associated with 9%-14% higher cholesterol concentrations in the small-size LDL. Long-chain PFCAs were negatively associated with the cholesterol and triglyceride concentrations in the large- and mid-sized VLDL subfractions. We found mostly negative associations between PFAS and inflammatory biomarkers. One IQR increase in PFOS, PFNA, PFDA, PFUnDA and PFDoDA was associated with 2-3% lower anti-inflammatory factors, HGF and IL-10RB. CONCLUSIONS:In this exploratory study, we aimed to identify serum lipoprotein and inflammatory biomarkers as markers of exposure to PFAS. We observed that PFAS exposure may influence the distribution and lipid composition of major lipoprotein subclasses, as well as modulation of inflammatory responses. KEYWORDS: Proteomics, PFAS, Cardiovascular diseases, Toxicology

Placental Transfer and Composition of Perfluoroalkyl Substances (PFASs): A Korean Birth Panel of Parent-Infant Triads.

Exposure to perfluoroalkyl substances (PFASs) is of public concern due to their persistent exposure and adverse health effects. Placental transfer of PFASs is an important excretion pathway of these chemicals in pregnant women and exposure route in fetuses. We measured PFAS concentrations in maternal, paternal, and umbilical cord serum collected from 62 pregnant Korean women and matched biological fathers of the fetuses. Placental transfer rates (cord to maternal serum ratio) of PFASs were also calculated. Demographics and pregnancy-related factors determining the placental transfer rates were identified using linear regression models. Maternal, paternal, and cord serum showed different PFASs compositions. Among the PFASs, perfluorooctane sulfonate (PFOS) showed the highest concentrations in maternal and paternal serum, while perfluorooctanoic acid (PFOA) showed the highest concentration in cord serum. There was a higher proportion of perfluoroalkyl carboxylic acids (PFCAs) with 9–12 carbon chains than those with 13–14 carbon chains in maternal and paternal serum, but this proportion was in the opposite direction in cord serum. PFOA and perfluorohexane sulfonate (PFHxS) had higher placental transfer rates (means of 0.32 and 0.36, respectively) than PFOS (mean of 0.12), which is in line with the results of previous studies. Gestational age and birth weight were positively associated with placental transfer rate of PFOA, PFHxS, and PFOS, while pre-pregnant BMI and weight were inversely associated with PFOS. This study showed that placental transfer of PFASs differs by compounds and is associated with pregnancy-related factors. Further studies on novel PFASs are warranted for Korean pregnant women.

Perfluoroalkyl substances (PFASs) exposure and kidney damage: Causal interpretation using the US 2003–2018 National Health and Nutrition Examination Survey (NHANES) datasets

IntroductionThe objective of this study was to validate the hypothesis that increased serum concentrations of perfluoroalkyl substances (PFASs) cause kidney damage. A causal interpretative study was designed using the US 2003–2018 National Health and Nutrition Examination Survey (NHANES) datasets. MethodsThree statistical models, including multivariable linear regression, generalized additive model, and regression discontinuity model (RDM), were applied to the US 2003–2018 NHANES datasets to evaluate the causal relationship between the four PFAS agents and estimated glomerular filtration rate (eGFR). Directed acyclic graphs were plotted for a more valid causal inference. Results and DiscussionIn the RDM, when the natural logarithm of each PFAS agent increases by 1 ng/mL after each cut-off value, eGFR decreased 4.63 mL/min/1.73 m2 for perfluorooctanoic acid, 3.42 mL/min/1.73 m2 for perfluorooctane sulfonic acid, 2.37 mL/min/1.73 m2 for perfluorohexane sulfonic acid, and 2.87 mL/min/1.73 m2 for perfluorononanoic acid. The possibility of reverse causation that increased serum PFAS concentration is the consequence of reduced eGFR, not the cause, was low, and an additional adjustment of potential confounders was not needed. ConclusionThis study contributes to the understanding of PFAS-induced kidney damage. Further longitudinal epidemiological and toxicological studies are recommended.

Premenopausal Osteoporosis & Perfluoroalkyl Substance Exposure; Is There a Link?

Introduction: Perfluoroalkyl substances (PFAS) like Perflouroctanoate (PFOA) and Perflurooctane sulfonate (PFOS) are ubiquitous environmental contaminants that have been in industrial use for many years. Many known adverse effects include malignancies, reproductive and thyroid dysfunction. However, there is limited literature regarding PFAS causing low bone density. We report a case of a premenopausal woman with a history of exposure to PFAS who was recently diagnosed with osteoporosis.Clinical Case: A 36-year-old lady with a history of hypothyroidism, on levothyroxine, presented to the orthopedics clinic with complaints of sudden onset right foot pain with no trauma. She was found to have a fracture of her right second metatarsal bone. Notably, over a period of five years she had suffered multiple fractures including metatarsal, elbow and a wrist fracture, all with minimal or no trauma. She denied smoking, alcohol, chronic steroid or PPI use, history of malabsorption, celiac disease, kidney stones, malignancy or liver problems. Her menstrual cycles were regular; she was on oral contraceptives in the past for dysmenorrhea. She is on Vitamin D supplementation and consumes adequate dairy products daily. There is no family history of hip fracture or osteoporosis. Labs showed: Calcium 8.9mg/dl, Phosphorus 2.4mg/dl (2.5–4.5mg/dl), intact PTH was 92.7pg/ml (8-97pg/ml), 24-hour urine calcium was undetectable. Vitamin D was 56.6ng/ml (30-100ng/ml). CBC, TSH, FSH, liver & kidney functions were all normal. Anti-endomysial, anti-gliadin and anti-tissue trans glutaminase antibodies were all unremarkable. IgA level was 362mg/dl (8–352 mg/dl). DXA scan revealed the lowest Z-score (-3.1) in the lumbar spine. She reported a history of exposure to PFAS with a blood level of 22.3ng/ml for PFOA and 48.4ng/ml for PFOS in the year 2005. Plan is to initiate bisphosphonate therapy for the treatment of osteoporosis.Discussion: PFAS are known endocrine disruptive agents that have been used widely in making a wide range of consumer products including nonstick and stain-resistant coatings of cookware, food containers. Recent studies suggest that serum PFAS concentrations were associated with lower bone density. There was a higher incidence of lower lumbar spine bone density in patients exposed to PFOS. PFOA is believed to compete with calcitriol at the same binding site on Vitamin D receptor resulting in changes in the osteoblasts thereby decreasing bone mineralization.Conclusion: There needs to be increased awareness about the association of low bone density in patients exposed to PFAS. This is especially important in the evaluation of premenopausal osteoporosis.