Perfluoroalkyl Acids Exposure Research Articles

Aggregated health risk assessment of perfluoroalkyl acids migrated from convenience food contact materials.

Ingestion of perfluoroalkyl acids (PFAAs) via contaminated food contact materials (FCMs) is an important human exposure source. This study adopts a toxicity equivalent approach to evaluate the collective health risk of multiple PFAAs in FCMs. A comprehensive extraction and analysis of 21 PFAAs in FCMs was performed. Among the analyzed substances, 15 PFAAs were detected. Migration experiment using three food simulants revealed the migration range of seven PFAAs from FCMs into the simulant to be 0.47-46.7ng/cm2. The hazard quotient results suggest minimal health risk, except for 9% of packaged samples where perfluorooctanoic acid (PFOA) poses a higher risk. Utilizing PFOA toxic equivalent concentrations, comprehensive risk calculations showed ∼77% of samples potentially posing elevated health risks due to PFAA exposure. This emphasizes the substantial contribution of PFAAs beyond PFOA and underscores the importance of considering them in related assessments. The aggregated risk assessment reflects actual exposure circumstances more accurately.

Characterizing Important Dietary Exposure Sources of Perfluoroalkyl Acids in Inuit Youth and Adults in Nunavik Using a Feature Selection Tool.

Previous studies have identified the consumption of country foods (hunted/harvested foods from the land) as the primary exposure source of perfluoroalkyl acids (PFAA) in Arctic communities. However, identifying the specific foods associated with PFAA exposures is complicated due to correlation between country foods that are commonly consumed together. We used venous blood sample data and food frequency questionnaire data from the Qanuilirpitaa? ("How are we now?") 2017 (Q2017) survey of Inuit individuals y of age residing in Nunavik (). Adaptive elastic net, a machine learning technique, identified the most important food items for predicting PFAA biomarker levels while accounting for the correlation among the food items. We used generalized linear regression models to quantify the association between the most predictive food items and six plasma PFAA biomarker levels. The estimates were converted to percent changes in a specific PFAA biomarker level per standard deviation increase in the consumption of a food item. Models were also stratified by food type (market or country foods). Perfluorooctanesulfonic acid (PFOS), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) were associated with frequent consumption of beluga misirak (rendered fat) [14.6%; 95% confidence interval (CI): 10.3%, 18.9%; 14.6% (95% CI: 10.1%, 19.0%)], seal liver [9.3% (95% CI: 5.0%, 13.7%); 8.1% (95% CI: 3.5%, 12.6%)], and suuvalik (fish roe mixed with berries and fat) [6.0% (95% CI: 1.3%, 10.7%); 7.5% (95% CI: 2.7%, 12.3%)]. Beluga misirak was also associated with higher concentrations of perfluorohexanesulphonic acid (PFHxS) and perfluorononanoic acid (PFNA), albeit with lower percentage changes. PFHxS, perfluorooctanoic acid (PFOA), and PFNA followed some similar patterns, with higher levels associated with frequent consumption of ptarmigan [6.1% (95% CI: 3.2%, 9.0%); 5.1% (95% CI: 1.1%, 9.1%); 5.4% (95% CI: 1.8%, 9.0%)]. Among market foods, frequent consumption of processed meat and popcorn was consistently associated with lower PFAA exposure. Our study identifies specific food items contributing to environmental contaminant exposure in Indigenous or small communities relying on local subsistence foods using adaptive elastic net to prioritize responses from a complex food frequency questionnaire. In Nunavik, higher PFAA biomarker levels were primarily related to increased consumption of country foods, particularly beluga misirak, seal liver, suuvalik, and ptarmigan. Our results support policies regulating PFAA production and use to limit the contamination of Arctic species through long-range transport. https://doi.org/10.1289/EHP13556.

Proteomic and cardiac dysregulation by representative perfluoroalkyl acids of different chemical speciation during early embryogenesis of zebrafish

Perfluoroalkyl acids (PFAAs) of different chemical speciation were previously found to cause diverse toxicity. However, the toxicological mechanisms depending on chemical speciation are still largely unknown. In this follow-up study, zebrafish embryos were acutely exposed to only one concentration at 4.67 μM of the acid and salt of representative PFAAs, including perfluorooctanoic acid (PFOA), perfluorobutane carboxylic acid (PFBA), and perfluorobutanesulfonic acid (PFBS), till 96 h post-fertilization (hpf), aiming to gain more mechanistic insights. High-throughput proteomics found that PFAA acid and salt exerted discriminative effects on protein expression pattern. Bioinformatic analyses based on differentially expressed proteins underlined the developmental cardiotoxicity of PFOA acid with regard to cardiac muscle contraction, vascular smooth muscle contraction, adrenergic signaling in cardiomyocytes, and multiple terms related to myocardial contraction. PFOA salt and PFBS acid merely disrupted the cardiac muscle contraction pathway, while cardiac muscle cell differentiation was significantly enriched in PFBA acid-exposed zebrafish larvae. Consistently, under PFAA exposure, especially PFOA and PFBS acid forms, transcriptional levels of key genes for cardiogenesis and the concentrations of troponin and epinephrine associated with myocardial contraction were significantly dysregulated. Moreover, a transgenic line Tg (my17: GFP) expressing green fluorescent protein in myocardial cells was employed to visualize the histopathology of developing heart. PFOA acid concurrently caused multiple deficits in heart morphogenesis and function, which were characterized by the significant increase in sinus venosus and bulbus arteriosus distance (SV-BA distance), the induction of pericardial edema, and the decrease in heart rate, further confirming the stronger toxicity of PFOA acid than the salt counterpart on heart development. Overall, this study highlighted the developmental cardiotoxicity of PFAAs, with potency ranking PFOA > PFBS > PFBA. The acid forms of PFAAs induced stronger cardiac toxicity than their salt counterparts, providing an additional insight into the structure-toxicity relationship.

The interaction of perfluoroalkyl acids and a family history of diabetes on arthritis: analyses of 2011–2018 NHANES

Whether a family history of diabetes (FHD) and exposure to perfluoroalkyl acids (PFAAs) are correlated with an increased risk of developing arthritis remains unclear. This cross-sectional study was conducted to explore the correlations between FHD or exposure to PFAAs and arthritis as well as their interaction using the National Health and Nutrition Examination Survey (NHANES). In total, 6,194 participants aged ≥ 20 years from the 2011–2018 NHANES were enrolled. PFAAs are a cluster of synthetic chemicals, including perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorodecanoic acid (PFDA) and perfluorohexane sulfonic acid (PFHxS). FHD was evaluated using self-reported questionnaires. Arthritis was classified into three types, rheumatoid arthritis (RA), osteoarthritis (OA), and others, which were diagnosed using questionnaires. Generalized linear models (GLMs) were used to test the correlation between FHD and arthritis. To examine the joint effects of PFAAs and FHD on arthritis, interaction terms were applied in the GLM. Arthritis incidence was 26.7% among all participants. FHD was associated with both RA [OR = 1.70 (95% CI: 1.15–2.50)] and other types of arthritis [OR = 1.62 (95% CI: 1.21–2.16)]. However, the relationship between FHD and OA was not significant after adjustment (P = 0.18). Interaction outcomes indicated that higher PFDA levels increased the association between FHD and arthritis. FHD is associated with an increased incidence of arthritis, which may be increased by PFDA. Given the heavy burden of arthritis, preventive measures for arthritis and reduction of PFAAs exposure for patients with FHD are required.

Factors affecting the occurrence and accumulation of perfluoroalkyl acids in indoor dust in Tainan, Taiwan

Perfluoroalkyl acids (PFAAs) are environmentally and biologically persistent chemicals. In this study, we investigated the concentrations of six PFAAs in dust samples collected from different indoor environments in a college campus in Tainan, Taiwan, and assessed the health risk of PFAAs exposure to college students. We also analyzed the effects of dust characteristics (total organic carbon, moisture content, and dust content) on PFAAs levels. With regard to the space type, the median of total PFAAs concentrations were in the order of laboratories (528.9 μg kg−1) > offices (304.2 μg kg−1) > dormitories (180.1 μg kg−1) > classrooms (105.1 μg kg−1). With regard to the height from the ground, the median total PFAAs concentrations were in the order of dust near the floors (>2 m; 383.6 μg kg−1) > near the ceiling (0–2 m; 202.5 μg kg−1) > on the ground (0 m; 145.6 μg kg−1). The main species of PFAAs, perfluorooctane sulfonate and short-chain perfluoroalkyl carboxylates, accounted for respectively 30%–60% and ∼20%–37% of total PFAAs pollution in the indoor space types and sampling heights under consideration. The average daily intake (ADI) values of six PFAAs for college students were found to be 0.059–0.126 ng kg−1 BW day−1 (BW: body weight), with dormitories and workplaces (i.e., laboratories and offices) accounting for over 40% and ∼50% of the ADI, respectively. The estimated hazard quotient ranged from 0.0029 to 0.0063, three orders of magnitude lower than 1, suggesting relatively low risks for college students exposed to the six PFAAs monitored in indoor dust. The analysis of dust characteristics revealed that total organic carbon did not have a significant effect on PFAAs levels as we expected. In contrast, dust moisture and cation content dominated PFAAs accumulation.

Prediction of perfluoroalkyl acids (PFAAs) in homegrown eggs: Insights into abiotic and biotic factors affecting bioavailability and derivation of potential remediation measures

Homegrown eggs from free-ranging laying hens often contain elevated concentrations of perfluoroalkyl acids (PFAAs). However, it is unclear which factors contribute to these relatively large exposure risk scenarios. Moreover, existing bioavailability and modeling concepts of conventional organic pollutants cannot be generalized to PFAAs due to their different physicochemical soil interactions. Therefore, there is an urgent need for empirical models, based on real-world data, to provide insights into how (a)biotic factors affect the bioavailability to eggs. To this end, 17 targeted analytes were analyzed in abiotic (i.e. rainwater, soil; both N = 101) matrices and homegrown eggs (N = 101), which were sampled in 101 private gardens across Flanders (Belgium) in 2019, 2021 and 2022. Various soil characteristics were measured to evaluate their role in affecting PFAA bioavailability to the eggs. Finally, PFAAs were measured in potential feed sources (i.e. homegrown vegetable and earthworm pools; respectively N = 49 and N = 34) of the laying hens to evaluate their contribution to the egg burden. Modeling suggested that soil was a major exposure source to laying hens, accounting for 16–55% of the total variation in egg concentrations for dominant PFAAs. Moreover, concentrations in vegetables and earthworms for PFBA and PFOS, respectively, were significantly positively related with corresponding egg concentrations. Predictive models based on soil concentrations, total organic carbon (TOC), pH, clay content and exchangeable cations were successfully developed for major PFAAs, providing possibilities for time- and cost-effective risk assessment of PFAAs in homegrown eggs. Among other soil characteristics, TOC and clay content were related with lower and higher egg concentrations for most PFAAs, respectively. This suggests that bioavailability of PFAAs to the eggs is driven by complex physicochemical interactions of PFAAs with TOC and clay. Finally, remediation measures were formulated that are readily applicable to lower PFAA exposure via homegrown eggs.

Cardiometabolic health and per and polyfluoroalkyl substances in an Inuit population

IntroductionThe cardiometabolic health status of Inuit in Nunavik has worsened in the last thirty years. The high concentrations of perfluoroalkyl acids (PFAAs) may be contributing to this since PFAAs have been linked with hypercholesterolemia, diabetes, and high blood pressure. The aim of this study was to examine the association between a PFAAs mixture and lipid profiles, Type II diabetes, prediabetes, and high blood pressure in this Inuit population. MethodsWe included 1212 participants of the Qanuilirpitaa? 2017 survey aged 16–80 years. Two mixture models (quantile g-computation and Bayesian Kernel Machine Regression (BKMR)) were used to investigate the associations between six PFAAs (PFHxS, PFOS, PFOA and three long-chain PFAAs (PFNA, PFDA and PFUnDA)) with five lipid profiles and three cardiometabolic outcomes. Non-linearity and interaction between PFAAs were further assessed. ResultsAn IQR increase in all PFAAs congeners resulted in an increase in total cholesterol (β 0.15, 95% confidence interval (CI) 0.06, 0.24), low-density lipoprotein cholesterol (LDL) (β 0.08, 95% CI 0.01, 0.16), high-density lipoprotein cholesterol (HDL) (β 0.04, 95% CI 0.002, 0.08), apolipoprotein B-100 (β 0.03, 95% CI 0.004, 0.05), and prediabetes (OR 1.80, 95% CI 1.11, 2.91). There was no association between PFAAs and triglycerides, diabetes, or high blood pressure. Long-chain PFAAs congeners were the main contributors driving the associations. Associations were largely linear, and there was no evidence of interaction between the PFAAs congeners. ConclusionsOur study provides further evidence of increasing circulating lipids with increased exposure to PFAAs. The increased risk of prediabetes points to the influence of PFAAs on potential clinical outcomes. International regulation of PFAAs is essential to curb PFAAs exposure and related health effects in Arctic communities.

Low concentrations of perfluoroalkyl acids (PFAAs) in municipal drinking water associated with serum PFAA concentrations in Swedish adolescents

While highly contaminated drinking water (DW) is a major source of exposure to perfluoroalkyl acids (PFAAs), the contribution of low-level contaminated DW (i.e. < 10 ng/L of individual PFAAs) to PFAA body burdens has rarely been studied. To address this knowledge gap, we evaluated the association between concentrations of perflurooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS) and perfluorooctane sulfonic acid (PFOS), and their sum (∑4PFAAs) in DW and serum in Swedish adolescents using weighted least squares regression. We paired serum PFAA concentrations in adolescents (age 10–21 years, n = 790) from the dietary survey Riksmaten Adolescents 2016–17 (RMA) with mean PFAA concentrations in water samples collected in 2018 from waterworks (n = 45) supplying DW to the participant residential and school addresses. The median concentrations of individual PFAAs in DW were < 1 ng/L. Median concentrations of PFNA and PFHxS in serum were < 1 ng/g, while those of PFOA and PFOS were 1–2 ng/g. Significant positive associations between PFAA concentrations in DW and serum were found for all four PFAAs and ∑4PFAAs, with estimated serum/DW concentration ratios ranging from 210 (PFOA) to 670 (PFHxS), taking exposure from sources other than DW (background) into consideration. The mean concentrations of PFHxS and ∑4PFAA in DW that would likely cause substantially elevated serum concentrations above background variation were estimated to 0.9 ng/L and 2.4 ng/L, respectively. The European Food Safety Authority has determined a health concern concentration of 6.9 ng ∑4PFAAs/mL serum. This level was to a large degree exceeded by RMA participants with DW ∑4PFAA concentrations above the maximum limits implemented in Denmark (2 ng ∑4PFAAs/L) and Sweden (4 ng ∑4PFAAs/L) than by RMA participants with DW concentrations below the maximum limits. In conclusion, PFAA exposure from low-level contaminated DW must be considered in risk assessment for adolescents.

Plasma concentrations of perfluoroalkyl acids and their determinants in youth and adults from Nunavik, Canada

Perfluoroalkyl acids (PFAAs), a subset of per- and poly-fluoroalkyl substances (PFAS), are environmentally stable, mobile and bioaccumulative compounds. This leads to high concentrations in wildlife species essential to the cultural identity and subsistence of Arctic populations. Our objective was to characterize the distribution and exposure determinants of PFAAs among Nunavik Inuit adults. The study included up to 1322 Nunavik residents aged 16–80 years who participated in the Qanuilirpitaa? 2017 Nunavik Inuit Health Survey (Q2017). Plasma concentrations were compared to those the general Canadian population using data from the Canadian Health Measures Survey Cycle 5 (2016–2017). Associations between plasma concentrations of nine PFAAs, determined by liquid chromatography-tandem mass spectrometry, and sociodemographic factors and traditional activity participation were examined using multiple linear regression models. Overall exposure to PFAAs was twice as high compared to the general Canadian population and less regulated perfluorononanoic acid (PFNA) and perfluoroundecanoic acid (PFUnDA) concentrations were 7-fold higher, and perfluorodecanoic acid (PFDA) concentrations were 4-fold higher. Males had higher concentrations of perfluorooctanoic acid (PFOA) and perfluorohexane sulfonate (PFHxS), whereas females had higher concentrations of PFDA and PFUnDA. PFAAs concentrations increased with age and were highest among those aged 60+ years. PFNA and PFOA concentrations followed a J-shaped pattern: those aged 16–29 years had higher concentrations than those aged 20–29 and 30–39 years. Ungava Bay generally had lower concentrations of all PFAAs congeners compared to Hudson Bay and Hudson Strait, with the exception of PFNA, which tended to have the lowest concentration in Hudson Strait. PFAAs concentrations were highly associated with hunting activity, omega-3 polyunsaturated fatty acids, and drinking water from environmental sources. The results highlight the importance of characterizing PFAAs exposure sources in Arctic communities and provide further evidence for the long-range transport of long-chain PFAAs and their precursors that necessitate international action.

Fatty acid ecological tracers highlight the role of diet in perfluoroalkyl acid contaminant exposure in eggs of an omnivorous bird

Herring gulls (Larus argentatus) are generalist feeders; contaminant levels in their eggs reflect chemical exposure and uptake due to foraging in both aquatic and terrestrial environments. Hence, contaminant levels in their eggs provide insights into sources and relative importance of aquatic versus terrestrial pathways of chemical transfer. Here, perfluoroalkyl acids (PFAAs) known to be bioaccumulative were measured in individual herring gull eggs from one site on Lake Superior, Ontario, Canada. Thirteen perfluorinated carboxylates (PFCA, C4-C18) and four perfluorinated sulfonates (PFSA, C4-C10) were measured. Total PFCA and total PFSA concentrations varied 4- and 5-fold, respectively, among eggs. To understand these differences, stable carbon and nitrogen isotopes and fatty acid dietary tracers were measured in the same eggs. Stable isotopes were not useful in explaining inter-egg differences in PFAA concentrations. However, a variety of omega 3 (n-3) and omega 6 (n-6) fatty acid measures were correlated with C9-C13 PFCAs as well as the PFSAs: perfluoro-1-hexanesulfonic acid (PFHxS) and perfluoro-1-octanesulfonic acid (PFOS). In general, n-3 fatty acids were positively correlated with egg PFAA concentrations while only the n-6 fatty acids exhibited negative relationships with egg PFAA levels. Proportions of n-3 and n-6 fatty acids in eggs would be expected to increase and decrease, respectively, with increased aquatic food in the gull diet. Results indicate that increased use of aquatic food led to heightened PFAA exposure in these generalist consumers sampled in a relatively remote area. They also highlight the utility of employing a variety of dietary markers for understanding contaminant exposure and accumulation.

Evaluated serum perfluoroalkyl acids and their relationships with the incidence of rheumatoid arthritis in the general population in Hangzhou, China

Perfluoroalkyl acids (PFAAs) are widely present in human blood, and have many toxic effects on humans. However, effects of PFAA exposure on the risk of rheumatic immune diseases are limited. In the present study, occurrence of 7 PFAAs, including perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoate (PFNA), perfluorodecanoate (PFDA), perfluoroundecanoate (PFUnA), perfluorododecanoate (PFDoA), and perfluorotrdecanoate (PFTrA), were measured in serum samples from 156 healthy people (controls) and 156 rheumatoid arthritis (RA) cases living in Hangzhou, China. We also investigated the relationships among cumulative PFAA levels in serum, some immune markers, and the incidence of RA. The results showed that PFOA (6.1 and 11.8 ng/mL) had the highest mean serum concentrations, followed by PFOS (3.2 and 3.4 ng/mL) and PFDA (0.86 and 2.6 ng/mL), in both controls and RA cases. Cumulative exposure to PFOA in the study population were positively correlated with the levels of rheumatoid factors (rs = 0.69, p < 0.01) and anti-cyclic citrullinated peptide antibody (rs = 0.56, p < 0.05). Moreover, significant associations of PFOA concentrations with odds ratios (OR) of RA (OR = 1.998, confidence interval (CI): 1.623, 2.361, p = 0.01) were found by adjusting for various covariates. The crude and adjusted OR for RA was respective 1.385 (95% CI: 1.270, 1.510, p = 0.04) and 1.381 (95% CI: 0.972, 1.658, p = 0.06) for a unit increase in serum PFOS levels, but the adjusted results were not significant. Overall, this case-control study found that human serum PFOA concentrations were positively correlated with RF and ACPA levels.

Potential disruption of thyroid hormones by perfluoroalkyl acids in an Arctic seabird during reproduction

Arctic marine ecosystems are experiencing rapid change, such as ocean warming and enhanced pollutants. Perfluoroalkyl acids (PFAAs) arriving via long-range transport have been detected in Arctic wildlife, including seabirds which are considered sentinels of marine ecosystem health. There is evidence that PFAA exposure leads to the disruption of thyroid hormones (THs), such as thyroxine (T4) and triiodothyronine (T3), which play important roles in metabolism, incubation, and thermoregulation in seabirds. Here, we investigated relationships between PFAAs and THs [total T4 (TT4), free T4 (FT4), total T3 (TT3) and free T3 (FT3)] in blood plasma collected from 63 thick-billed murres (Uria lomvia) at a colony located in northern Hudson Bay (2016–2018). We then tested if PFAAs and TH levels were related to fitness-associated reproductive traits, such as body mass and hatch dates. PFUdA, PFOS, and PFTrDA were the dominant PFAAs in murre blood, accounting for approximately 77% of ∑PFAA. Females had higher PFAAs than males, possibly due to higher trophic feeding. While FT3 increased with PFOS, PFNA, PFDA, PFDoA, PFTeDA, ∑PFCA7, and ∑PFAA in murres, TT3 decreased with PFOS, PFDoA, and PFTeDA in males, but not females, suggesting thyroid disruption. TT3 increased with body mass, whereas several long-chain PFAAs were negatively correlated with body mass. Negative relationships between PFNA, PFDoA, PFTrDA, PFTeDA, and ∑PFAA with hatch dates may be the result of a disruption in incubation behaviour, resulting in earlier hatch dates. Consequently, TT3 concentrations were highest in males and females in 2018, a year in which PFAAs were lowest and hatch dates were delayed relative to 2017. As an Arctic seabird experiencing several indirect effects of climate change, the interaction of PFAAs on thyroid activity may cause additional stress to murres.

Influence of perfluoroalkyl acids and other parameters on circulating thyroid hormones and immune-related microRNA expression in free-ranging nestling peregrine falcons

Exposure to certain perfluoroalkyl acids (PFAAs) can have considerable effects on the endocrine and immune systems, although such effects remain largely uncharacterized in wildlife. Using an apex avian predator, we investigated possible relationships of thyroid hormones (THs), specifically free (F) and total (T) thyroxine (FT4; TT4) and triiodothyronine (FT3; TT3), and the expression of an immune-related microRNA biomarker (i.e., miR-155), with the concentrations of 11 PFAAs in nestling peregrine falcons (Falco peregrinus). Nestling peregrines (n = 56; usually two chicks of each sex per nest) were blood sampled when 23 ± 4 days old in urban and rural regions of the Laurentian Great Lakes Basin (Ontario, Canada) in 2016 and 2018. The circulating concentrations of several PFAAs were significantly associated with THs and estimated thyroid gland activity (TT3:TT4; FT3:FT4), including PFHxS (FT3; FT3:FT4), PFDS (TT3; TT3:TT4), PFOA (TT4; FT3:FT4), PFTeDA (TT4; FT3:FT4), PFHxDA (TT4; TT3:TT4) and ΣPFCAs (TT4). Our novel evaluation of miR-155 in peregrine nestlings identified significantly negative relationships of plasma miR-155 counts with PFHxS and PFOA concentrations, indicating potential down-regulation of miR-155 expression and impaired immunity. Several PFAA homologues significantly predicted the variation in THs and miR-155 in conjunction with year (e.g., inter-annual differences in weather, ambient temperature, rainfall), region (urban/rural), nestling age, and/or diet (trophic position; δ15N), which suggests that multiple environmental and biological stressors, including PFAA exposure, influenced thyroid activity and immune function in these nestlings. Further research is warranted to identify the mechanisms and additional impacts of PFAA-related thyroid and immune disruption on the growth, development, and health risks in developing birds.

Understanding PFAAs exposure in a generalist seabird species breeding in the vicinity of a fluorochemical plant: Influence of maternal transfer and diet.

Perfluoroalkyl acids (PFAAs) are a focus of scientific and regulatory attention nowadays. However, PFAAs dynamics in the environment and the factors that determine wildlife exposure are still not well understood. In this study we examined PFAAs exposure in chicks of a generalist seabird species, the lesser black-backed gull (Larus fuscus), breeding 49km away of a PFAAs hotspot (a fluorochemical plant in Antwerp, Belgium). In order to study the pathways of PFAAs exposure, we measured how chicks' PFAAs burden varied with age, sex, and body condition. In addition, we related PFAA concentrations to chicks' diet using stable isotope signatures. For this purpose, we studied plasma PFAA concentrations in 1-week and 4-week-old gull chicks. Only 4 (PFOS, PFOA, PFDA and PFNA) out of the 13 target PFAA compounds were detected. Measured concentrations of PFOS and PFOA were generally high compared to other seabird species but were highly variable between individuals. Furthermore, our results suggest that maternal transfer plays a significant role in determining chicks' PFAAs burden, and that there are variable sources of exposure for PFOS and PFOA during post-hatching development. The association between PFOS and specific stable isotopes (i.e. δ15N and δ13C) suggests a higher exposure to PFOS in birds with a predominantly marine diet. We also found that males' condition was positively associated with PFOS plasmatic concentration, probably due to the indirect effect of being fed a high quality (marine) diet which appears PFOS rich. Yet, exact exposure source(s) for PFOA remain(s) unclear. Given that PFOS concentrations measured in some chicks surpassed the toxicity reference value calculated for top avian predators, continued monitoring of exposure and health of this gull population, and other wildlife populations inhabiting the area, is highly recommended.

Assessing the human health risks of per- and polyfluoroalkyl substances: A need for greater focus on their interactions as mixtures

Humans are exposed to complex mixtures of per- and polyfluoroalkyl substances (PFAS). However, human health risk assessment of PFAS currently relies on animal toxicity data derived from individual substance exposure, which may not adequately predict the risk from combined exposure due to possible interactions that can influence the overall risk. Long-chain perfluoroalkyl acids (PFAAs), particularly perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are recognised as global emerging contaminants of concern due to their ubiquitous distribution in all environmental media, wildlife, and humans, persistency, bioaccumulative-, toxic-, and human health-risk potentials. This article reviews the current understanding of the human health risks associated with PFAS exposure focusing on more recent toxicological and epidemiological studies from 2010 to 2020. The existing information on PFAA mixtures was also reviewed in an attempt to highlight the need for greater focus on their potential interactions as mixtures within the class of these chemicals. A growing number of toxicological studies have indicated several adverse health outcomes of PFAA exposure, including developmental and reproductive toxicity, neurotoxicity, hepatotoxicity, genotoxicity, immunotoxicity, thyroid disruption, and carcinogenicity. Epidemiological findings further support some of these adverse human health outcomes. However, the mechanisms underlying these adverse effects are not well defined. A few in vitro studies focusing on PFAA mixtures revealed that these compounds may act additively or interact synergistically/antagonistically depending on the species, dose level, dose ratio, and mixture components. Hence, the combined effects or potential interactions of PFAS mixtures should be considered and integrated into toxicity assessment to obtain a realistic and more refined human health risk assessment.

The Impact of Smoking on the Association between Perfluoroalkyl Acids (PFAS) and Thyroid Hormones: A National Health and Nutrition Examination Survey Analysis.

Perfluoroalkyl acids (PFAS) are known endocrine disrupting chemicals, potentially affecting thyroid function. Smoking has been associated with PFAS levels as well as with thyroid function. The impact of smoking on the association between PFAS and thyroid function remains to be elucidated, so the objective was to assess the effect of PFAS exposure on thyroid function in the general population, stratified by smoking status, using the National Health and Nutrition Examination Survey (NHANES). NHANES adult participants who were part of the 2011–2012 laboratory subsample and had PFAS and thyroid function measured were included (n = 1325). Adjusted linear regression models and stratified analyses were performed. There was a significant positive association between perfluorooctanesulfonic acid (PFOS) (p = 0.003), perfluorononanoic acid (PFNA) (p = 0.014), total PFAS (p = 0.004) concentrations and free T4 (FT4). No significant associations were found between perfluorooctanoic acid (PFOA), PFOS, perfluorohexane sulfonate (PFHxS), PFNA, total PFAS and total T4 (TT4) or thyroid stimulating hormone (TSH). In non-smokers, a significant positive association was found between PFOS (p = 0.003), PFHxS (p = 0.034), PFNA (p = 0.012), total PFAS (p = 0.003) and FT4 while no significant associations were found in smokers. The present study showed that increased PFAS exposure was associated with increased FT4 in non-smokers, while no association was found in smokers. These results confirm that smoking modifies the association between PFAS exposure and thyroid function.

Human-Based Exposure Levels of Perfluoroalkyl Acids May Induce Harmful Effects to Health by Disrupting Major Components of Androgen Receptor Signalling In Vitro

Perfluoroalkyl acids (PFAAs) are detectable in human blood. PFAA exposure may contribute to androgen receptor (AR)-related health effects such as prostate cancer (PCa). In Norway and Sweden, exposures to PFAAs and PCa are very real concerns. In vitro studies conventionally do not investigate PFAA-induced AR disruption at human blood-based concentrations, thus limiting application to human health. We aim to determine the endocrine disrupting activity of PFAAs based upon human exposure levels, on AR transactivation and translocation. PFAAs (PFOS, PFOA, PFNA, PFDA, PFHxS, and PFUnDA) were tested at concentrations ranging from 1/10 × to 500 × relative to human blood based upon the exposure levels observed in a Scandinavian population. Translocation was measured by high content analysis (HCA) and transactivation was measured by reporter gene assay (RGA). No agonist activity (translocation or transactivation) was detected for any PFAAs. In the presence of testosterone, AR translocation increased following exposure to PFOS 1/10 × and 100 ×, PFOA 1/10 ×, and PFNA 1 × and 500 × (P < 0.05). In the presence of testosterone, PFOS 500 × antagonised AR transactivation, whereas PFDA 500 × increased AR transactivation (P < 0.05). PFAAs may contribute to AR-related adverse health effects such as PCa. PFAAs can disrupt AR signalling via two major components: translocation and transactivation. PFAAs which disrupt one signalling component do not necessarily disrupt both. Therefore, to fully investigate the disruptive effect of human exposure-based contaminants on AR signalling, it is imperative to analyse multiple molecular components as not all compounds induce a disruptive effect at the same level of receptor signalling.

Sex differences in the association between perfluoroalkyl acids and liver function in US adolescents: Analyses of NHANES 2013–2016

Perfluoroalkyl acids (PFAAs) are persistent in the environment, highly bio-accumulative in the body, and likely hepatotoxic in humans. There is evidence of sex-specific physiological responses to PFAA exposure. However, epidemiological studies seldom stratify the analyses by sex. Given the high prevalence of liver disease in general population adolescents, this study was designed to determine whether or not there is association between exposure to PFAAs and biomarkers of liver function in adolescent participants of the 2013–2016 National Health and Nutrition Examination Survey, and whether or not such association is sex-specific. Multivariate linear regressions were performed to examine the association between single PFAAs [perfluorooctane sulfonic acid (PFOS); linear form of perfluorooctanoic acid (PFOA); perfluorohexane sulfonic acid (PFHxS); perfluorononanoic acid (PFNA)], and biomarkers of liver function — gamma glutamyltransferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin. Multivariate logistic regressions were performed to estimate adjusted odd ratios (aOR) of elevated ALT, AST and GGT. The study results show that, in females, there was a positive association of the highest PFOA quartile with increased ALT, AST and GGT, and the highest PFNA quartile with increased ALT and AST. Conversely, in male adolescents there was an association of the highest linear PFOA quartile with decreased ALT, and the highest PFNA quartile with ALT and AST. Females had higher odds of clinically-defined elevated ALT with increased PFOA (aOR = 1.79; 95% CI: 1.05, 3.04) or PFNA (aOR = 2.28; 95% CI: 1.08, 2.28), whereas males had decreased odds of clinically-defined elevated ALT with increased n-PFOA (aOR = 0.43; 95% CI: 0.20, 0.93) or PFNA (aOR = 0.5; 95% CI: 0.28, 0.89). In conclusion, there were sex differences in the association between serum PFAA levels and biomarkers of liver function. These results may provide support for analyzing sex-based adverse effects of PFAAs.

Exposure of Juncus effusus to seven perfluoroalkyl acids: Uptake, accumulation and phytotoxicity

The extensive use of poly- and perfluoroalkyl substances (PFAS) has led to perfluoroalkyl acids (PFAAs) contamination in various environmental matrices. To remove PFAAs from contaminated water, this study investigated plant uptake of PFAAs by a native wetland plant species in the US, Juncus effusus. The results showed that J. effusus translocated selected PFAAs, including perfluoropentanoic acid (PFPA), perfluorobutanesulfonic acid (PFBS), perfluorohexanoic acid (PFHxA), perfluoroheptanoic acid (PFHpA), perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), and perfluorooctanesulfonic acid (PFOS). During the 21-day experimental period, the uptake of PFAAs increased with increasing PFAAs exposure concentration and time. PFOS was largely accumulated in the roots with limited upward translocation. PFAAs with shorter carbon chain length were taken up by J. effusus roots and tended to accumulate in plant shoots. The highest removal efficiency (11.4%) of spiked PFAAs by J. effusus was achieved when it was exposed to PFAAs at around 4.6 mg/L for 21 days. The exposure to PFAAs stimulated the antioxidative defense system in J. effusus shoots but inhibited the superoxide dismutase (SOD) and catalase (CAT) activities and damaged the antioxidative defense system in J. effusus roots. These results warrant further studies to evaluate J. effusus's long-term performance in a PFAAs contaminated environment.

Dietary Exposure of Chinese Adults to Perfluoroalkyl Acids via Animal-Origin Foods: Chinese Total Diet Study (2005-2007 and 2011-2013).

Diet has been regarded as the main exposure source of perfluoroalkyl acids (PFAAs), but the national dietary survey of PFAAs in China was limited. Here, eight typical PFAAs were detected in milk, aquatic food, meat, and eggs from the Chinese Total Diet Studies (TDSs) during 2005-2007 and 2011-2013. Aquatic food was found to be the main source of PFAAs among animal-origin foods. The estimated dietary intakes of ∑PFAAs from animal foods (EDIanimal-originfoods) in coastal areas were relatively higher than in inland areas. The highest EDIanimal-originfoods of PFOS [4.07 and 2.02 ng kg-1 of body weight (bw) day-1] and PFOA (2.19 ng kg-1 of bw day-1) found in Shanghai and perfluorononanoic acid (PFNA, 2.72 ng kg-1 of bw day-1) in Fujian approach or exceed current minimal risk levels from the Agency for Toxic Substances and Disease Registry and tolerable weekly intakes from the European Food Safety Authority, suggesting potential risk of PFAA exposure from animal-origin foods in these areas.