Perfluoroalkyl Substances Exposure Research Articles

Exposure to perfluoroalkyl substances and risk of hepatocellular carcinoma in a multiethnic cohort

Background & AimsExposure to poly- and perfluoroalkyl substances (PFAS), a class of persistent organic pollutants, is ubiquitous. Animal studies suggest that PFAS may increase risk of fatty liver and hepatocellular carcinoma (HCC) via impacts on hepatic lipid, amino acid, and glucose metabolism, but human data is lacking. We examined associations between PFAS exposure, altered metabolic pathways, and risk of non-viral HCC.MethodsIn this nested case-control study, pre-diagnostic plasma PFAS and metabolomics were measured in 50 incident HCC cases and 50 individually matched controls from the Multiethnic Cohort (MEC) study. Cases/controls were matched by age, sex, race, and study area. PFAS exposure and risk of HCC were examined using conditional logistic regression. A metabolome-wide association study and pathway enrichment analysis was performed for PFAS exposure and HCC risk, and key metabolites/metabolic pathways were identified using a meet in the middle approach.ResultsHigh perfluorooctane sulfonic acid (PFOS) levels (90th percentile from NHANES; >55 μg/L) were associated with 4.5-fold increased risk of HCC (odds ratio 4.5, 95% CI 1.2-16.0). Pathway enrichment analysis showed that PFOS exposure was associated with alterations in amino acid and glycan biosynthesis pathways, which were also associated with HCC risk. We identified 4 metabolites linking PFOS exposure with HCC, including glucose, butyric acid (a short-chain fatty acid), α-ketoisovaleric acid (a branched-chain α-keto acid), and 7α-hydroxy-3-oxo-4-cholestenoate (a bile acid), each of which was positively associated with PFOS exposure and risk of HCC.ConclusionThis proof-of-concept analysis shows that exposure to high PFOS levels was associated with increased risk of non-viral HCC, likely via alterations in glucose, amino acid, and bile acid metabolism. Larger studies are needed to confirm these findings.Lay summaryPer- and polyfluoroalkyl substances (PFAS), often referred to as “forever chemicals” because they are difficult to break down and stay in the human body for years, are extremely common and can cause liver damage. In a first of its kind study, we found that exposure to high levels of perfluorooctanesulfonic acid, one of the most common PFAS chemicals, was linked to increased risk of hepatocellular carcinoma in humans. Hepatocellular carcinoma is difficult to treat and is one of the most common forms of liver cancer, and these findings may provide new avenues for helping to prevent this disease.

Associations of serum perfluoroalkyl substances with concentrations of blood manganese and selenium.

The aim of this study was to estimate the associations of blood manganese and selenium with serum concentrations of selected perfluoroalkyl substances (PFAS). The presence or absence of this association is important because PFAS have documented pro-oxidant properties, whereas manganese and selenium are critical to antioxidant responses. For this purpose, the data from NHANES for US adults aged ≥ 20years (N = 3982), adolescents aged 12-19years (N = 1524), and children aged 3-11years (N = 639) were analyzed. Among adults, concentrations of blood manganese were found to be inversely associated with serum concentrations of perfluorooctanoic acid or PFOA (β = - 0.04204, p < 0.01), perfluorononanoic acid or PFNA (β = - 0.02700, p < 0.01), perfluorohexane sulfonate or PFHxS (β = - 0.04306, p < 0.01), and perfluorooctane sulfonate or PFOS (β = - 0.04494, p < 0.01). Blood concentrations of selenium were found to be positively associated with PFHxS only among adults (β = 0.000678, p = 0.047) and adolescents (β = 0.01377, p = 0.02). The Mn results but not the less consistent Se associations were robust to adjustments for serum albumin. Possible reasons for the inverse association of PFOA, PFHxS, PFNA, and PFOS with Mn among US adults are discussed. The finding raises concerns about manganese's diminished ability to mount antioxidant responses to PFAS exposure.

Associations between prenatal exposure to perfluoroalkyl substances and neurobehavioral development in early childhood: A prospective cohort study

Findings from epidemiological studies on the associations between prenatal perfluoroalkyl substances (PFASs) exposure and children's neurodevelopment were inconclusive, and most studies did not account for the co-exposure to multiple PFASs with strong inter-correlations. The present study aimed to assess the effects of prenatal multiple PFAS exposure on children’s neurobehavioral development based on 614 mother-infant pairs in the Shanghai-Minhang Birth Cohort Study. Eight PFAS concentrations were measured in maternal plasma at 12–16 weeks of gestation. Children’s neurobehavioral development at 2 and 4 years of age was assessed by the Child Behavior Checklist for Ages 1.5–5. In Bayesian kernel machine regression (BKMR) analyses that could address the inter-correlations between multiple PFASs, PFAS mixture appeared to be associated with fewer Somatic Complaints and more Externalizing Problems in boys, but more Somatic Complaints and Sleep Problems in girls. There were suggestive associations of PFNA and PFOS with decreased risk of Somatic Complaints and of PFUdA and PFTrDA with increased risk of Externalizing Problems in boys; trends of increased risk in girls were observed between PFUdA and Somatic Complaints and between PFTrDA and Sleep Problems. Overall, we found no clear evidence that prenatal exposure to PFASs had negative effects on neurobehavioral development in children. However, the modest associations still suggested the potential developmental neurotoxicity of prenatal PFAS exposure.

Per- and polyfluoroalkyl substances exposure and bone mineral density in the U.S. population from NHANES 2005-2014.

Environmental exposures such as perfluoroalkyl substances (PFASs) were considered potential risks for bone mineral density (BMD). To examine the associations between PFASs and BMD among the U.S. population. This study included a total of 6416 participants from the National Health and Nutrition Examination Survey (NHANES 2005-2014). Multiple linear regression models were used to analyze the associations between serum PFASs and BMD and the coefficient β with 95% confidence intervals (95% CI) was calculated as the effect estimate. Covariates such as age, race, BMI, smoking, alcohol intake, milk intake, and physical activity were adjusted in these models. Additionally, gender and menopausal period were considered in further subgroup analyses. Based on the combined data of NHANES 2005-2014, the effects from exposure to PFASs on BMD were found with gender and menopausal status differences. Positive associations were found in PFOA (β = 0.010; 95% CI: 0.003, 0.016), PFHxS (β = 0.007; 95% CI: 0.003, 0.012), and PFNA (β = 0.001; 95% CI: 0.001, 0.017) in total population. Negative associations for PFOA (β = -0.020; 95% CI: -0.029, -0.012), PFOS (β = -0.011; 95% CI: -0.028, -0.011), PFHxS (β = -0.019; 95% CI: -0.025, -0.013), PFDE (β = -0.010; 95% CI: -0.016, -0.005), and PFNA (β = -0.011; 95% CI: -0.021, -0.002) were found in women, while no significant association was found in men. In further subgroup analyses, women in pre-menopause status showed consistent negative associations. PFASs exposure may be associated with BMD and gender and menopausal status confound the associations.

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.

Poly- and perfluoroalkyl substances (PFAS) exposure through infant feeding in early life.

Per- and polyfluoroalkyl substances (PFAS) are non-degradable, man-made-chemicals with an elimination half-life of multiple years, causing accumulation in the environment and humans with potential harmful effects. However, longitudinal PFAS levels in human milk, daily PFAS intake and the association with infant plasma PFAS levels have never been reported. We investigated longitudinal PFOA and PFOS levels in human milk and the daily PFAS intake through infant feeding in the first 3months of life, the most important determinants and the correlation with PFAS plasma levels at age 3months and 2years. In 372 healthy term-born Dutch infants, we determined PFOA and PFOS levels in human milk given at age 1 and 3months, in 6 infant formula brands and in infant plasma at 3months and 2years, using liquid-chromatography-electrospray-ionization-tandem-mass-spectrometry(LC-ESI-MS/MS). We studied the associations between daily PFAS intake and predictive characteristics by multiple regression models. PFOA and PFOS levels in human milk decreased between 1 and 3months after delivery, regardless whether breastfeeding was given exclusively(EBF) or in combination with formula feeding. PFOA and PFOS could not be detected in any formula feeding. Daily PFAS intake(ng/kg) was highest in EBF-infants. Higher amount of human milk, older maternal age, lower parity and first-time breastfeeding were associated with higher daily intake. Daily PFAS intake in early life was strongly correlated with PFAS plasma levels at age 3months and 2years(R=0.642-0.875, p<0.001). Human milk contains PFOA and PFOS, in contrast to formula feeding. Daily PFOA and PFOS intake in early life is highest in exclusively breastfed infants and it is highly correlated with infant's plasma levels throughout infancy. Our findings show that breastfeeding is an important PFAS exposure pathway in the first months of life, with unknown but potential adverse effects. Knowing the important health benefits of breastfeeding, our findings warrant more research about the health outcomes in later life.

Plasma perfluoroalkyl substance exposure and incidence risk of breast cancer: A case-cohort study in the Dongfeng-Tongji cohort

Experimental studies have suggested perfluoroalkyl substances (PFASs) as mammary toxicants, but few studies evaluated the prospective associations of PFASs with breast cancer risk. We performed a case-cohort study within the Dongfeng-Tongji cohort, including incident breast cancer cases (n = 226) and a random sub-cohort (n = 990). Baseline plasma concentrations of four perfluorinated carboxylic acids (PFCAs) [perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroheptanoic acid (PFHpA)] and two perfluorinated sulfonic acids (PFSAs) [perfluorooctane sulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS)] were measured. Barlow-weighted Cox regression models revealed that each 1-unit increase in ln-transformed PFOA and PFHpA was associated with a separate 35% and 20% elevated incident risk of breast cancer [HR(95%CI) = 1.35(1.03, 1.78) and 1.20(1.02, 1.40), respectively], which were also significant among postmenopausal females [HR(95%CI) = 1.34(1.01, 1.77) and 1.23 (1.02, 1.48), respectively]. Quantile g-computation analysis observed a 19% increased incident risk of breast cancer along with each simultaneous quartile increase in all ln-transformed PFCA concentrations [HR(95%CI) = 1.19(1.01, 1.41)], with PFOA accounting for 56% of the positive effect. Our findings firstly revealed the impact of short-chain PFHpA on increased incident risk of breast cancer, suggested exposure to PFASs as a risk factor for breast cancer, and shed light on breast cancer prevention by regulating PFASs as a chemical class.

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.

Human exposure pathways to poly- and perfluoroalkyl substances (PFAS) from indoor media: A systematic review.

Human exposure to per- and polyfluoroalkyl substances (PFAS) has been primarily attributed to contaminated food and drinking water. There is information indicating other sources and pathways of exposure in residential environments, but few studies report relationships between these indoor media and human biomonitoring measurements. This study adapts existing systematic review tools and methodologies to synthesize evidence for PFAS exposure pathways from indoor environment media including consumer products, household articles, cleaning products, personal care products, and indoor air and dust. Studies were identified using innovative machine learning approaches and pathway-specific search strings to reduce time needed for literature search and screening. The included studies and systematic review were evaluated using tools modified specifically for exposure studies. The systematic review was conducted following a previously published protocol (DeLuca et al., 2021) that describes the systematic review methodology used in detail. Only 7 studies were identified that measured the targeted subset of 8 PFAS chemicals in concordant household media (primarily house dust) and participant serum. Data extracted from the included studies were used to calculate exposure intake rates and estimate a percentage of occupant serum concentrations that could be attributed to the indoor exposure pathways. These calculations showed that exposure to PFOA, PFOS, PFNA, and PFHxS from contaminated house dust could account for 13%, 3%, 7%, and 25% of serum concentrations, respectively. Inhalation of PFAS in indoor air could account for less than 4% of serum PFOA concentrations and less than 2% of serum PFOS and PFNA concentrations. A risk of bias was identified due to participant profiles in most of the studies being skewed towards white, female, and higher socioeconomic status. Along with synthesizing evidence for estimated contributions to serum PFAS levels from indoor exposure media, this systematic review also identifies a consistent risk of bias across exposure study populations that should be considered in future studies. It highlights a major research gap and need for studies that measure concordant data from both indoor exposure media and participant serum and the need for continued research on exposure modeling parameters for many PFAS chemicals.

Associations between prenatal exposure to perfluoroalkyl substances, hypomethylation of MEST imprinted gene and birth outcomes

Prenatal perfluoroalkyl substance (PFAS) exposure has been linked to adverse birth outcomes, but the underlying mechanism has yet to be elucidated. DNA methylation changes in mesoderm-specific transcript (MEST) imprinted gene may be a mechanism of the prenatal exposure effects of PFASs on fetal growth. The aim was to investigate the prenatal PFASs exposure effects on DNA methylation changes in MEST imprinted gene involved in fetal growth. Among 486 mother-infant pairs from the Taiwan Birth Panel Study, PFASs and DNA methylation levels at 5 CpG sites of MEST promoter region were measured in cord blood. Univariable and multivariable linear regressions were performed to estimate the associations between prenatal PFAS exposure, MEST DNA methylation levels, and child birth outcomes. Mediation analysis was performed to examine the potential pathway of MEST methylation between PFASs and birth outcomes. We found that higher prenatal perfluorooctyl sulfonate (PFOS) exposure was significantly associated with lower methylation levels at 5 CpG sites of MEST promoter region (an adjusted β range: −1.56, −2.22). Significant negative associations were also found between MEST methylation levels and child birth weight. Furthermore, the associations between PFOS and perfluorooctanoic acid (PFOA) exposure and MEST methylation levels were more profound in girls than in boys. The mediated effect of average MEST methylation level between PFOS exposure and birth weight was 18.3 (95% CI = 2.1, 40.2; p = 0.014). The direct effect of PFOS exposure to birth weight independent to average MEST methylation level was −93.2 (95% CI = −170.5, −17.8; p = 0.018).In conclusion, our results suggest that prenatal PFAS exposure, especially PFOS, is associated with lower methylation levels at MEST promoter region, which not only leverages the role of imprinted gene in ensuring the integrity of fetal growth but also provides a potential mechanism for evaluating the prenatal exposure effect.

The relationship between multiple perfluoroalkyl substances and cardiorespiratory fitness in male adolescents.

Exposure to perfluoroalkyl substances (PFASs) is associated with a number of adverse health outcomes. However, the relationship between mixed and individual PFAS exposure and cardiorespiratory fitness (CRF) in adolescents remains unclear. We used cross-sectional data from 491 teenagers (aged 13-19years) from the 2003-2004 National Health and Nutrition Examination Survey (NHANES) and examined the association between mixed PFAS exposure and CRF via weighted quantile sum (WQS) regression. Maximal oxygen consumption (VO2max) was used to evaluate CRF. Multivariate linear regression was performed to investigate the relationship between each PFAS and VO2max as well as the relationship between PFAS exposure and the inflammation parameters and blood lipid content. Mediation analyses were performed to investigate possible explanations of the risk of low CRF due to PFAS exposure. The results showed that for males, mixed PFAS exposure was negatively related to VO2max (beta = - 0.80, 95% CI: - 1.53 to - 0.10, P = 0.028) and that of the PFASs, perfluorononanoic acid (PFNA) had the greatest influence on VO2max. In the individual PFAS analysis, PFNA was negatively related to VO2max in male adolescents (beta = - 1.49, 95% CI: - 2.65 to - 0.32, P = 0.013). Additionally, significant relationships among serum PFNA levels and total cholesterol and the white blood cell (WBC) count were found. Mediation analyses revealed that WBC count accounted for 24.18% of the variation between PFNA level and CRF. The present results provide epidemiological evidence that exposure to PFASs, mainly PFNA, is negatively associated with CRF, possibly via alterations in WBC count.

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

Association between per- and polyfluoroalkyl substances and risk of gestational diabetes mellitus.

Existing evidence suggests that perfluoroalkyl and polyfluoroalkyl substances (PFASs) exposure might contribute to the incidence of gestational diabetes mellitus (GDM). This study aimed to perform a meta-analysis to identify the association between PFAS and the risk of GDM. We systematically searched PubMed, Ovid, Cochrane Library, and Web of Science databases for appropriate articles about the association between PFASs exposure and the risk of GDM before September 28, 2020. Odds ratios (OR) with 95% confidence intervals (CIs) were summarized by Stata 16.0 through fixed effect models according to heterogeneity. We also carried out subgroup analyses by geographic location, blood sampling time of subjects, method of chemical analysis, study design, sample size, and sampling year. In addition, a sensitivity analysis was conducted to explore the robustness of the results. A total of eight studies involving 5654 pregnant women were included in the meta-analysis. Perfluorooctanoic acid (PFOA) exposure was positively and significantly associated with the risk of GDM (OR=1.27, 95% CI: 1.02-1.59). Exposure to other types of PFASs such as perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA) was not statistically significantly associated with the risk of GDM with the pooled effect estimates of 0.97 (95% CI: 0.86-1.09), 1.03 (95% CI: 0.86-1.24), and 0.80 (95% CI: 0.55-1.16) respectively. We conducted a meta-analysis to investigate the association between PFASs exposure and GDM and found that PFOA concentration was significantly associated with a higher risk of GDM, which is of great significance for the prevention and control of GDM in public health. Further studies are needed in order to establish causality and clarify the potential mechanism.

Longitudinal poly- and perfluoroalkyl substances (PFAS) levels in Dutch infants.

Per- and polyfluoroalkyl substances (PFAS) are a potential hazard for public health. These man-made-chemicals are non-degradable with an elimination half-life of multiple years, causing accumulation in the environment and humans. Rodent studies demonstrated that PFAS are harmful, especially when present during the critical window in the first months of life. Because longitudinal data during infancy are limited, we investigated longitudinal plasma levels in infants aged 3months and 2years and its most important determinants. In 369 healthy term-born Dutch infants, we determined plasma PFOS, PFOA, PFHxS, PFNA and PFDA levels at age 3months and 2years, using liquid chromatography-electrospray-ionization-tandem-mass-spectrometry (LC-ESI-MS/MS). We studied the associations with maternal and child characteristics by multiple regression models. At age 3months, median plasma levels of PFOS, PFOA, PFHxS, PFNA and PFDA were 1.48, 2.40, 0.43, 0.23 and 0.07ng/mL, resp. Levels decreased slightly until age 2years to 1.30, 1.81, 0.40, 0.21 and 0.08ng/mL, resp. Maternal age, first born, Caucasian ethnicity and exclusive breastfeeding were associated with higher infant's plasma levels at age 3months. Levels at 3months were the most important predictor for PFAS levels at age 2years. Infants with exclusive breastfeeding during the first 3months of life (EBF) had 2-3 fold higher levels throughout infancy compared to infants with exclusive formula feeding (EFF), with PFOA levels at 3months 3.72ng/mL versus 1.26ng/mL and at 2years 3.15ng/mL versus 1.22ng/mL, respectively. Plasma PFAS levels decreased only slightly during infancy. Higher levels at age 3months were found in Caucasian, first-born infants from older mothers and throughout infancy in EBF-infants. Our findings indicate that trans-placental transmission and breastfeeding are the most important determinants of PFAS exposure in early life.

Mixed effects of perfluoroalkyl and polyfluoroalkyl substances exposure on cognitive function among people over 60years old from NHANES.

The relationship between perfluoroalkyl and polyfluoroalkyl substances (PFAS) and cognitive function are inconsistent, and the mixed effects of PFAS on cognitive function are still unclear. We aimed to evaluate the joint effects of PFAS on cognitive function assessed using four tests as follows: the Consortium to Establish a Registry for Alzheimer's Disease Immediate Recall Test (IRT), Delayed Recall Test (DRT), the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST) in the US elderly. A total of 777 individuals aged ≥ 60 from the National Health and Nutrition Examination Survey (NHANES) 2011-2014 were included in this study. Multivariable logistic regression and Bayesian kernel machine regression (BKMR) were constructed to estimate the overall and the individual effects of PFAS exposure on cognitive function. There were 21.36%, 22.65%, 21.62%, and 21.24% participants with cognitive decline in IRT, DRT, AFT, and DSST, respectively. After multivariable adjustment, perfluorooctanoic acid (PFOA) was inversely associated with cognitive decline in IRT, DRT, and AFT, while no significant association was observed between any other PFAS and cognitive decline. Compared with the lowest quartile, the adjusted odds ratio of cognitive decline with a 95% confidence interval (CI) for the highest quartile of PFOA was 0.33 (95% CI: 0.15-0.69) in IRT, 0.50 (0.26-0.96) in DRT, and 0.45 (0.21-0.95) in AFT. In BKMR analysis, the overall effect of mixtures was significantly protective on cognitive decline in IRT, of which PFOA made the greatest contribution. The consistent protective effect in DRT and DSST was observed when all the chemicals were at their 50th percentile or below it. No significant interaction was observed among PFAS for cognitive function. These findings suggested that PFAS mixture at a low level of current exposure of the US population may have a protective effect on cognitive function.

The association between prenatal perfluoroalkyl substance exposure and symptoms of attention-deficit/hyperactivity disorder in 8-year-old children and the mediating role of thyroid hormones in the Hokkaido study.

Disruption of thyroid hormone (TH) levels during pregnancy contributes to attention deficit hyperactivity disorder (ADHD). Exposure to perfluoroalkyl substances (PFAS) during gestation may affect levels of maternal and neonatal TH; however, little is known about the effect of PFAS on ADHD mediated by TH. We investigated the impact of maternal PFAS exposure on children's ADHD symptoms with the mediating effect of TH. In a prospective birth cohort (the Hokkaido study), we included 770 mother-child pairs recruited between 2002 and 2005 for whom both prenatal maternal and cord blood samples were available. Eleven PFAS were measured in maternal serum obtained at 28-32weeks of gestation using ultra-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry. TH and thyroid antibody, including thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) were measured in maternal blood during early pregnancy (median 11 gestational weeks) and in cord blood at birth. ADHD symptoms in the children at 8years of age were rated by their parents using the ADHD-Rating Scale (ADHD-RS). The cut-off value was set at the 80th percentile for each sex. Significant inverse associations were found between some PFAS in maternal serum and ADHD symptoms among first-born children. Assuming causality, we found only one significant association: maternal FT4 mediated 17.6% of the estimated effect of perfluoroundecanoic acid exposure on hyperactivity-impulsivity among first-born children. Higher PFAS levels in maternal serum during pregnancy were associated with lower risks of ADHD symptoms at 8years of age. The association was stronger among first-born children in relation to hyperactivity-impulsivity than with regard to inattention. There was little mediating role of TH during pregnancy in the association between maternal exposure to PFAS and reduced ADHD symptoms at 8years of age.

Presence of perfluoroalkyl substances in Mediterranean sea and North Italian lake fish addressed to Italian consumer

SummaryThe primary source of perfluoroalkyl substances (PFASs) exposure is the diet, mainly fish. Seabass (Dicentrarchus labrax) and seabream (Sparus aurata) are among the most consumed sea fish in Italy. Fish from Northern Italy lakes like perch (Perca fluviatilis) is of particular importance in terms of consumption volume, while Mediterranean shad (Alosa agone) and European whitefish (Coregonus lavaretus) represent niche consumption. These species too could be a cause of consumer exposure to PFAS. The study investigated the presence of PFASs in the above‐mentioned fish species through LC‐HRMS analysis. Only PFBA and PFOS were found both in lake and sea fish while PFBS was found only in lake fish. The found concentrations were used to estimate intake of PFOS, the only detected molecule of the four discussed in the last EFSA report. The Tolerable Weekly Intake of 4.4 ng kg−1 b.w. per week was never exceeded also for the 99th percentile consumers.

Association between maternal serum concentration of perfluoroalkyl substances (PFASs) at delivery and acute infectious diseases in infancy

BackgroundPerfluoroalkyl substances (PFASs) are persistent and bio-accumulative compounds that have been recognized as important immune hazards by animal studies. However, epidemiological studies regarding the impact on infant infections were inconsistent. ObjectivesWe investigated the associations between prenatal exposure to PFASs and acute infectious diseases including common cold, bronchitis/pneumonia, and diarrhea in early childhood. MethodsParticipating 235 mother–infant pairs were recruited from the Laizhou Wan (Bay) birth cohort (LWBC), a prospective study in Shandong, China between September 2010 and 2013. Ten selected PFASs congeners including PFOA, PFOS, PFNA, PFDA, PFUA, PFDoA, PFHxS, PFBS, PFHpA, and PFOSA were measured from maternal serum by HPLC-MS/MS. Detailed information on parent-reported frequency of acute infectious diseases was collected from questionnaires at 1-year follow-up, which was confirmed by the medical records. Logistic and Poisson regression models were used on binary health outcomes (yes/no) and the number of episodes of outcomes, which were reported as odds ratio (OR) and incidence rate-ratio (IRR), respectively. ResultsThe risk of diarrhea increased by 4.99 (95% CI = 1.86, 13.39) per log-unit increase in PFOA. The frequencies of diarrhea increased by 97%–116% for each 10-fold increase in PFOA, PFNA, and PFDA. Moreover, when stratified by exclusively breastfeeding duration (at least 4 months or not), the adverse effects of PFASs exposures on diarrhea were more pronounced among the breastfed infants. There were no associations between prenatal PFASs exposure and common cold or bronchitis/pneumonia. ConclusionsExposure to PFASs was associated with increased risks of diarrhea during the first year of life, and these effects were stronger among the breastfed infants. Due to the small sample size, our results should be interpreted with caution and additional studies on larger populations are needed to confirm our findings.

Perfluoroalkyl substances (PFAS) in drinking water and risk for polycystic ovarian syndrome, uterine leiomyoma, and endometriosis: A Swedish cohort study.

Perfluorinated substances (PFAS) are chemicals with endocrine disruptive properties that may interfere with the female reproductive system. However, few studies have explored the association between benign gynecological diseases and high PFAS exposure. The aim of this study was to investigate the possible associations between PFAS exposure and subsequent diagnosis of polycystic ovarian syndrome (PCOS), uterine leiomyoma (fibroids), and endometriosis in a cohort exposed to PFAS through drinking water. In 2013, high levels (with sum of PFAS above 10,000ng/L), dominated by perfluorooctanesulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS), were found in the drinking water from one of the two waterworks in Ronneby, Sweden. The contamination came from firefighting foams used at a nearby airfield. Females of all ages (n=29,106) who had ever resided in the municipality between 1985 and 2013 formed a cohort. Individual exposure was assessed based on municipality waterworks distribution data linked to annual residential address data; 27% of the females had ever lived at an address with PFAS-contaminated water. Gynecological health outcomes were retrieved from the Swedish National Patient Register. The Cox proportional hazards model was used to estimate the association between exposure and each diagnosis. There were in all 161 cases of PCOS, 1,122 cases of uterine leiomyoma, and 373 cases of endometriosis. In women aged 20-50years (n=18,503), those with the highest estimated PFAS exposure had increased hazard ratios (HR) for PCOS (HR=2.18; 95% confidence interval (CI) 1.43, 3.34) and uterine leiomyoma (HR=1.28; 95% CI 0.95, 1.74). No increased HR for endometriosis was found (HR=0.74; 95% CI 0.42, 1.29). Exposure to high levels of PFAS in drinking water was associated with increased risk of PCOS and possibly uterine leiomyoma, but not endometriosis. The findings for PCOS are consistent with prior studies reporting positive associations between PCOS and PFAS exposure at background levels.

Prenatal exposure to poly-/per-fluoroalkyl substances is associated with alteration of lipid profiles in cord-blood

IntroductionPoly-/per-fluoroalkyl substances (PFAS) are widespread environmental pollutants that may induce metabolic perturbations in humans, including particularly alterations in lipid profiles. Prenatal exposure to PFAS can cause lasting effects on offspring metabolic health, however, the underlying mechanisms are still unknown.ObjectivesThe goal of the study was to investigate the impact of prenatal PFAS exposure on the lipid profiles in cord blood.MethodsHerein, we combined determination of bile acids (BAs) and molecular lipids by liquid chromatography with ultra-high-resolution mass spectrometry, and separately quantified cord blood concentrations of sixteen PFAS in a cohort of Chinese infants (104 subjects) in a cross-sectional study. We then evaluated associations between PFAS concentration and lipidome using partial correlation network analysis, debiased sparse partial correlation, linear regression analysis and correlation analysis.ResultsPFAS levels showed significant associations with the lipid profiles; specifically, PFAS exposure was positively correlated with triacylgycerols (TG) and several bile acids. Importantly, exposure to perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA) and perfluorohexane sulfonic acid (PFHxS) were associated with increased levels of TGs with saturated fatty acids while multiple classes of phospholipids were decreased. In addition, several free fatty acids showed significant positive correlations with PFOS.ConclusionsOur results indicated that prenatal exposure to PFAS mediated metabolic changes, which may explain the associations reported between PFAS exposure and metabolic health later in life.