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Tree swallow nest boxes were deployed at sites proximal to two putative aqueous film forming foam (AFFF) sources in the Duluth, MN area, as well as along the St. Louis River and a reference lake for comparative purposes in 2019, 2020 and 2021. The two AFFF sites were the current Duluth Air National Guard Base (ANG) and the Lake Superior College Emergency Response Training Center. Between 13 and 40 per- and polyfluoroalkyl substances (PFAS), depending on year, were detected and quantified in tree swallow egg, nestling carcasses, and stomach contents. Assessments were made of oxidative stress and ethoxyresorufin-O-dealkylase activity in liver tissue, thyroid hormone levels in plasma and thyroid glands, DNA damage in red blood cells, and two measures of immune response (haptoglobin-like activity and immunoglobulin) in plasma of the nestlings. Additionally, other contaminants, such as polychlorinated biphenyls, legacy organochlorine pesticides, and trace elements, were assessed at sites with no previous data. Total egg PFAS concentrations at the ANG site and north of that site were 30–40 times higher than at the reference lake, while nestling PFAS concentrations were 10–15 times higher. In contrast, the St. Louis River sites had slightly, but non-statistically significant, elevated egg and nestling PFAS concentrations relative to the reference lake (2–5 times higher). One PFAS, perfluorohexane sulfonate (PFHxS), was higher, as a proportion of total PFAS, at sites with a known AFFF source compared to the reference lake, as well as compared to sites along the St. Louis River with mainly urban and industrial sources of PFAS. The ratio of total carboxylates to total sulfonates also distinguished between PFAS sources. There were few to no differences in biomarker responses among sites, and no association with PFAS exposure. [ABSTRACT FROM AUTHOR]

Per- and polyfluoroalkyl substances have the potential to leach into groundwater, particularly in areas with potential pollution sources, such as landfills. The composition and distribution of per- and polyfluoroalkyl substances, as well as soil characteristics, are particularly useful for identifying the sources of per- and polyfluoroalkyl substances. The objectives of the present study were to characterise per- and polyfluoroalkyl substance levels in groundwater in Thailand, identify their potential sources and highlight their spatial distribution. Groundwater samples were collected in areas hosting municipal and industrial waste disposal sites. Seven Per- and polyfluoroalkyl substances were extracted from the groundwater samples using the solid-phase extraction technique and analysed by high-performance liquid chromatography-tandem mass spectrometry. These samples contain mostly perfluorooctanoic acid and perfluorooctane sulfonate, with the highest concentrations of 34.96 and 25.88 ng L–1, respectively, obtained from industrial waste disposal site areas. The presence of perfluorohexane sulfonate in most samples from industrial waste disposal site areas suggests its usage as a substitute for perfluorooctane sulfonate-based products. In addition to waste disposal, hierarchical cluster analysis reveals that other sources likely influence the presence of per- and polyfluoroalkyl substances in groundwater in Thailand. Livestock farming and ponds near groundwater wells probably impact per- and polyfluoroalkyl substances levels in the associated groundwater. The spatial distribution of per- and polyfluoroalkyl substances shows that in addition to waste disposal sources, soil characteristics and interactions between their negatively charged components and cations in soils significantly influence the contamination of groundwater in the areas studied. [ABSTRACT FROM AUTHOR]

Background: The successive FLEHS campaigns assess internal exposure to pollutants and associated early biological and health effects in participants of different age groups. Materials and methods: Mother–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. Results: For 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. Conclusion: Internal 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. [ABSTRACT FROM AUTHOR]

Background: PFAS are persistent, bioaccumulative compounds repelling water, oil and stains which are widely used. There is mounting evidence linking exposure to a range of adverse health outcomes including renal, hepatic, immunotoxic, reproductive, endocrine disrupting and carcinogenic effects. PFAS possibly also induce neurobehavioral and developmental effects. Within Flanders Environment and Health Studies (FLEHS) internal exposure to PFAS and relevant health effects are assessed since 2008. Results: Adolescents 14–15 y (2010–2011) living in an industrially contaminated area (without known PFAS contamination) and adults 50–65 y (2014) randomly sampled from the general Flemish population using a stratified clustered multi-stage design, were recruited. For the adolescents perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) were measured in serum, for the adults PFOS, PFOA, perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA) and perfluorobutane sulfonate (PFBS). In adolescents the Neurobehavioral Evaluation System (NES3) computerized battery of tests developed to study the neurological effects of an exposure to environmental agents was applied. The adults did the Stroop test, the NES3 Continuous Performance Test and the NES3 Digit Span Test. In adolescents sleepiness, masculinity and femininity were assessed via the Epworth Sleepiness Scale and Personal Attributes Questionnaires, respectively. In adolescents PFOA was associated with significantly increased somnolence, and PFOS with a significant inverse association with boys' femininity and with girls' masculinity. In adolescents, PFAS were also associated with a marginal decrease in sustained attention (PFOS) and cognitive performance (PFOA) and a significant decrease in short-term memory (PFOS). However, in older adults PFOS was associated with a significant increase in the capacity to pay attention and PFHxS with a significant increase in sustained attention. Conclusion: Our observations point to neurobehavioral and cognitive effects of PFAS. The neurobehavioral effects might in part result from the changes in sex hormone levels that have been reported to be associated with internal exposure to PFAS. Interestingly, whereas in relation to cognition some adverse effects were recorded for adolescents, for elderly persons our observations rather suggest possible weak positive effects with respect to cognition. Our observations might be in line with the view that PFAS have many, sometimes contrasting health effects. [ABSTRACT FROM AUTHOR]

Background: Perfluorohexane sulfonate (PFHxS) is a six-carbon perfluoroalkyl sulfonic acid found as an environmental contaminant. This study aims to investigate the effects of PFHxS exposure on female reproduction and the underlying mechanism in mice. Methods: Eight-week-old ICR mice were divided randomly into four groups administered corn oil (vehicle) and PFHxS at doses of 0.5, 5, and 50 mg/kg/day for 42 days by intragastric administration. Body weight, ovarian weight, estrous cycle, follicle counts, and serum sex hormone levels were evaluated. The expression of kisspeptin and gonadotropin releasing hormone (GnRH) in the hypothalamus was also detected. Results: Compared to vehicle exposure, 5 mg/kg/day PFHxS treatment prolonged the estrous cycle, especially the duration of diestrus, after 42 days of treatment. The numbers of secondary follicles, antral follicles and corpus lutea were significantly reduced in the PFHxS-treated mice. Moreover, compared with the control mice, the PFHxS-treated mice showed decreases in the serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estrogen (E2), and reduced GnRH mRNA levels, along with the lack of an LH surge. Furthermore, the PFHxS-treated mice had lower levels of kisspeptin immunoreactivity and kiss-1 mRNA in the arcuate nucleus (ARC) and anteroventral periventricular nucleus (AVPV) than the control mice. After intraventricular administration of kisspeptin-10, the numbers of secondary follicles, antral follicles and corpus lutea recovered, along with the levels of GnRH mRNA, FSH, and LH in the mice treated with 5 mg/kg/day PFHxS. Conclusion: These results indicate that chronic exposure of mice to 5 mg/kg/day PFHxS affects reproductive functions by inhibiting kisspeptin expression in the ARC and AVPV regions, leading to deficits in follicular development and ovulation. [ABSTRACT FROM AUTHOR]

Perfluoroalkyl sulfonates (PFSAs) such as perfluorohexane sulfonate (PFHxS) and perfluorooctane sulfonate (PFOS) have very long serum elimination half-lives in humans, and preferentially distribute to serum and liver. The enterohepatic circulation of PFHxS and PFOS likely contributes to their extended elimination half-lives. We previously demonstrated that perfluorobutane sulfonate (PFBS), PFHxS, and PFOS are transported into hepatocytes both in a sodium-dependent and a sodium-independent manner. We identified Naþ/taurocholate cotransporting polypeptide (NTCP) as the responsible sodium-dependent transporter. Furthermore, we demonstrated that the human apical sodium-dependent bile salt transporter (ASBT) contributes to the intestinal reabsorption of PFOS. However, so far no sodium-independent uptake transporters for PFSAs have been identified in human hepatocytes or enterocytes. In addition, perfluoroalkyl carboxylates (PFCAs) with 8 and 9 carbons were shown to preferentially distribute to the liver of rodents; however, no rat or human liver uptake transporters are known to transport these PFCAs. Therefore, we tested whether PFBS, PFHxS, PFOS, and PFCAs with 7-10 carbons are substrates of organic anion transporting polypeptides (OATPs). We used CHO and HEK293 cells to demonstrate that human OATP1B1, OATP1B3, and OATP2B1 can transport PFBS, PFHxS, PFOS, and the 2 PFCAs (C8 and C9). In addition, we show that rat OATP1A1, OATP1A5, OATP1B2, and OATP2B1 transport all 3 PFSAs. In conclusion, our results suggest that besides NTCP and ASBT, OATPs also are capable of contributing to the enterohepatic circulation and extended human serum elimination half-lives of the tested perfluoroalkyl acids. [ABSTRACT FROM AUTHOR]

Early life neuronal exposure to environmental toxicants has been suggested to be an important etiology of neurodegenerative disease development. Perfluorohexanesulfonate (PFHxS), one of the major perfluoroalkyl compounds, is widely distributed environmental contaminants. We have reported that PFHxS induces neuronal apoptosis via ERK-mediated pathway. Imperatorin is a furanocoumarin found in various edible plants and has a wide range of pharmacological effects including neuroprotection. In this study, the effects of imperatorin on PFHxS-induced neuronal apoptosis and the underlying mechanisms are examined using cerebellar granule cells (CGC). CGC were isolated from sevenday old rats and were grown in culture for seven days. Caspase-3 activity and TUNEL staining were used to determine neuronal apoptosis. PFHxS-induced apoptosis of CGC was significantly reduced by imperatorin and PD98059, an ERK pathway inhibitor. PFHxS induced a persistent increase in intracellular calcium, which was significantly blocked by imperatorin, NMDA receptor antagonist, MK801 and the L-type voltage-dependent calcium channel blockers, diltiazem and nifedipine. The activation of caspase-3 by PFHxS was also inhibited by MK801, diltiazem and nifedipine. PFHxS-increased ERK activation was inhibited by imperatorin, MK801, diltiazem and nifedipine. Taken together, imperatorin protects CGC against PFHxSinduced apoptosis via inhibition of NMDA receptor/intracellular calcium-mediated ERK pathway. [ABSTRACT FROM AUTHOR]

Among the perfluoroalkyl sulfonates (PFASs), perfluorohexane sulfonate (PFHxS), and perfluorooctane sulfonate (PFOS) have half-lives of several years in humans, mainly due to slow renal clearance and potential hepatic accumulation. Both compounds undergo enterohepatic circulation. To determine whether transporters involved in the enterohepatic circulation of bile acids are also involved in the disposition of PFASs, uptake of perfluorobutane sulfonate (PFBS), PFHxS, and PFOS was measured using freshly isolated human and rat hepatocytes in the absence or presence of sodium. The results demonstrated sodium-dependent uptake for all 3 PFASs. Given that the Na+/taurocholate cotransporting polypeptide (NTCP) and the apical sodium-dependent bile salt transporter (ASBT) are essential for the enterohepatic circulation of bile acids, transport of PFASs was investigated in stable CHO Flp-In cells for human NTCP or HEK293 cells transiently expressing rat NTCP, human ASBT, and rat ASBT. The results demonstrated that both human and rat NTCP can transport PFBS, PFHxS, and PFOS. Kinetics with human NTCP revealed Km values of 39.6, 112, and 130 µM for PFBS, PFHxS, and PFOS, respectively. For rat NTCP Km values were 76.2 and 294 µM for PFBS and PFHxS, respectively. Only PFOS was transported by human ASBT whereas rat ASBT did not transport any of the tested PFASs. Human OSTα/β was also able to transport all 3 PFASs. In conclusion, these results suggest that the long half-live and the hepatic accumulation of PFOS in humans are at least, in part, due to transport by NTCP and ASBT. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What is the effect of maternal exposure to perfluorooctane sulfonate (PFOS), perflurooctanoic acid (PFOA) and perfluorohexane sulfonate (PFHxS) on female fecundity? SUMMARY ANSWER Increasing concentrations of PFOA or PFHxS in maternal plasma were associated with reduced fecundability and infertility. WHAT IS KNOWN ALREADY Perfluorinated chemicals (PFCs) are a group of synthetic compounds used in industrial production. There is a concern about the effect of PFCs on fecundity, as measured by time-to-pregnancy (TTP). Although some recent studies suggest that increasing concentrations of PFCs may decrease fecundity, divergence in the methodological approaches used to evaluate this association have prevented firm conclusions being reached. STUDY DESIGN, SIZE, DURATION The Maternal-Infant Research on Environmental Chemicals (MIREC) Study is a cohort study of 2,001 women recruited before 14 weeks of gestation in 10 cities across Canada between 2008 and 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS A questionnaire was administered and medical chart data and biospecimens were collected from participants. After excluding women who withdrew, those for whom data were incomplete, those whose pregnancies followed birth control failure, and accounting for male fertility, 1743 participants remained. TTP was defined as the number of months of unprotected intercourse needed to become pregnant in the current pregnancy, as self-reported in the first trimester of pregnancy. Plasma concentrations of PFOA, PFOS and PFHxS measured in the first trimester were considered as a surrogate of preconception exposure. Fecundability odds ratios (FORs) were estimated using Cox proportional hazard models for discrete time. FOR < 1 denote a longer TTP and FORs >1 denote a shorter TTP. The odds of infertility (TTP > 12 months or infertility treatment in the index pregnancy) were estimated using logistic regression. Each chemical concentration (ng/ml) was log-transformed and divided by its SD. MAIN RESULTS AND THE ROLE OF CHANCE The cumulative probabilities of pregnancy at 1, 6 and 12 months were 0.42 (95% confidence interval (CI) 0.40–0.45), 0.81 (95% CI 0.79–0.83) and 0.90 (95% CI 0.89–0.92), respectively. The mean maternal age was 32.8 (SD 5.0) years. The geometric means (ng/ml) of PFOA, PFOS and PFHxS were 1.66 (95% CI 1.61–1.71), 4.59 (95% CI 4.46–4.72) and 1.01 (95% CI 0.97–1.05), respectively. After adjustment for potential confounders, PFOA and PFHxS were associated with a 11 and 9% reduction in fecundability per one SD increase (FOR = 0.89; 95% CI 0.83–0.94; P < 0.001 for PFOA and FOR = 0.91; 95% CI 0.86–0.97; P = 0.002 for PFHxS), while no significant association was observed for PFOS (FOR = 0.96; 95% CI 0.91–1.02; P = 0.17). In addition, the odds of infertility increased by 31% per one SD increase of PFOA (odds ratio (OR) = 1.31; 95% CI 1.11–1.53; P = 0.001) and by 27% per one SD increase of PFHxS (OR = 1.27; 95% CI 1.09–1.48; P = 0.003), while no significant association was observed for PFOS (OR = 1.14; 95% CI 0.98–1.34; P = 0.09). LIMITATIONS, REASONS FOR CAUTION Women with the highest concentrations of PFCs might have been excluded from the study if there is a causal association with infertility. The MIREC study did not assess concentrations of PFCs in males, semen quality, menstrual cycle characteristics or intercourse frequency. WIDER IMPLICATIONS OF THE FINDINGS Our results add to the evidence that exposure to PFOA and PFHxS, even at lower levels than previously reported, may reduce fecundability. STUDY FUNDING/COMPETING INTEREST(S) The MIREC study is supported by the Chemicals Management Plan of Health Canada, the Canadian Institutes for Health Research (CIHR, grant no. MOP – 81285) and the Ontario Ministry of the Environment. M.P.V. ... [ABSTRACT FROM PUBLISHER]

Background: Prenatal exposures to polyfluoroalkyl compounds (PFCs) may be associated with adverse changes in fetal and postnatal growth. Objective: We explored associations of prenatal serum concentrations of perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorohexane sulfonate (PFHxS) with fetal and postnatal growth in girls. Methods: We studied a sample of 447 singleton girls and their mothers participating in the Avon Longitudinal Study of Parents and Children (ALSPAC). Data on weight and length were obtained at birth and at 2, 9, and 20 months. Serum samples were obtained in 1991-1992, from mothers during pregnancy. We explored associations between prenatal PFC concentrations and weight at birth as well as longitudinal changes in weight-for-age SD scores between birth and 20 months. Results: PFOS (median, 19.6 ng/mL), PFOA (median, 3.7 ng/mL), and PFHxS (median, 1.6 ng/mL) were detected in 100% of samples. On average, girls born to mothers with prenatal concentrations of PFOS in the upper tertile weighed 140 g less [95% confidence interval (CI):-238, -42] at birth than girls born to mothers with concentrations in the lower tertile in adjusted models. Similar patterns were seen for PFOA (-133 g; 95% CI: -237, -30) and PFHxS (-108 g; 95% CI: -206, -10). At 20 months, however, girls born to mothers with prenatal concentrations of PFOS in the upper tertile weighed 580 g more (95% CI: 301, 858) when compared with those in the lower tertile. No differences in weight were found for PFOA and PFHxS. Conclusions: Girls with higher prenatal exposure to each of the PFCs examined were smaller at birth than those with lower exposure. In addition, those with higher exposure to PFOS were larger at 20 months. [ABSTRACT FROM AUTHOR]