Polyfluoroalkyl Substances Exposure Research Articles

Systematic evidence mapping of potential correlates of exposure for per- and poly-fluoroalkyl substances (PFAS) based on measured occurrence in biomatrices and surveys of dietary consumption and product use

Per- and poly-fluoroalkyl substances (PFAS) are widely observed in environmental media and often are found in indoor environments as well as personal-care and consumer products. Humans may be exposed through water, food, indoor dust, air, and the use of PFAS-containing products. Information about relationships between PFAS exposure sources and pathways and the amounts found in human biomatrices can inform source-contribution assessments and provide targets for exposure reduction. This work collected and collated evidence for correlates of PFAS human exposure as measured through sampling of biomatrices and surveys of dietary consumption and use of consumer products and articles. A systematic evidence mapping approach was applied to perform a literature search, conduct title-abstract and full-text screening, and to extract primary data into a comprehensive database for 16 PFAS. Parameters of interest included: sampling dates and locations, cohort descriptors, PFAS measured in a human biomatrix, information about food consumption in 11 categories, use of products/articles in 11 categories, and reported correlation values (and their statistical strength). The literature search and screening process yielded 103 studies with information for correlates of PFAS exposures. Detailed data were extracted and compiled on measures of PFAS correlations between biomatrix concentrations and dietary consumption and other product/article use. A majority of studies (61/103; 59%) were published after 2015 with few (8/103; 8%) prior to 2010. Studies were most abundant for dietary correlates (n = 94) with fewer publications reporting correlate assessments for product use (n = 56), while some examined both. PFOA and PFOS were assessed in almost all studies, followed by PFHxS, PFNA, and PFDA which were included in >50% of the studies. No relevant studies included PFNS or PFPeS. Among the 94 studies of dietary correlates, significant correlations were reported in 83% of the studies for one or more PFAS. The significant dietary correlations most commonly were for seafood, meats/eggs, and cereals/grains/pulses. Among the 56 studies of product/article correlates, significant correlations were reported in 70% of the studies. The significant product/article correlations most commonly were for smoking/tobacco, cosmetics/toiletries, non-stick cookware, and carpet/flooring/furniture and housing. Six of 11 product/article categories included five or fewer studies, including food containers and stain- and water-resistant products. Significant dietary and product/article correlations most commonly were positive. Some studies found a mix of positive and negative correlations depending on the PFAS, specific correlate, and specific response level, particularly for fats/oils, dairy consumption, food containers, and cosmetics/toiletries. Most of the significant findings for cereals/grains/pulses were negative correlations. Substantial evidence was found for correlations between dietary intake and biomatrix levels for several PFAS in multiple food groups. Studies examining product/article use relationships were relatively sparse, except for smoking/tobacco, and would benefit from additional research. The resulting database can inform further assessments of dietary and product use exposure relationships and can inform new research to better understand PFAS source-to-exposure relationships. The search strategy should be extended and implemented to support living evidence review in this rapidly advancing area.

Bystanders to a Public Health Crisis

Per- and polyfluoroalkyl substances (PFAS) are devastating our food systems and our health. Due to widespread use, these synthetic, long-lasting chemicals, are omnipresent at dangerous levels in our envi-ronment and our homes. Recent studies link even small exposure to PFAS to a host of adverse health outcomes, including cancer, autoim-mune diseases, thyroid disease, liver damage, childhood obesity, infer-tility, and birth defects. Food consumption is a primary route of PFAS exposure. PFAS mi-grate from water, soil, fertilizers, pesticides, and compost into virtually every plant, fish, animal, and animal product, and ultimately (in the greatest concentration) into the consumer. In addition, food pro-cessing equipment, disposable dishes, and containers leach dangerous levels of these chemicals into processed food products, further infusing our every meal with PFAS. Consequently, it is no surprise everything from chocolate cake and microwave popcorn to free range eggs, wildcaught fish, organic milk, and organic kale can harbor staggering quantities of these toxic substances. Despite the widespread presence of these substances and strong sci-entific evidence of their harmful impact on humans, federal regulation of PFAS in food is currently nonexistent. At least fifteen agencies have a mandate to ensure the safety of our food. More is not always better. In the case of regulatory agencies, it can lead to fragmented demand for attention, diffusion of responsibilities, and bureaucratic bystander apathy. This story has played out time and again with other toxic con-taminants like polychlorinated biphenyls (PCBs) and pesticides and is playing out yet again with PFAS. Despite our country’s devastating experience with past contaminants and the unprecedented scientific progress of our time, the federal response to new food safety threats has only become more sluggish and inadequate. This article lays a pathway for change, taking the issue of PFAS food contamination as a case study for the broader dysfunction in the food safety regulatory system. Part II reviews the history of federal food regulation and explores the role that each federal actor in the field plays in ensuring the safety of the food supply. Part III provides back-ground on the chemical and toxicological profile of PFAS and their widespread presence in the environment in general and the food sup-ply in particular. Part IV examines possible approaches to more effec-tive regulation of environmental contaminants in food and proposes a readily available but currently overlooked mechanism for combatting the current public health crisis of PFAS in food. Lastly, Part V cata-logues the expected benefits of the solution and addresses anticipated skepticism. It concludes that the proposed approach can effectively protect consumers from PFAS in food today, while simultaneously gar-nering much needed data to usher in a more permanent solution in the future.

Unveiling the intricate connection between per- and polyfluoroalkyl substances and prostate hyperplasia

The presence of perfluoroalkyl and polyfluoroalkyl substances (PFAS) in various everyday products has raised concerns about their potential impact on prostate health. This study aimed to investigate the effects of different types of PFAS on prostate health, including PFDeA, PFOA, PFOS, PFHxS, and PFNA. To assess the relationship between PFAS exposure and prostate injury, machine learning algorithms were employed to analyze prostate-specific antigen (PSA) metrics. The analysis revealed a linear and positive dose-dependent association between PFOS and the ratio of free PSA to total PSA (f/tPSA). Non-linear dose-response relationships were observed between the other four types of PFAS and the f/tPSA ratio. Additionally, the analysis showed a positive association between the mixture of PFAS and prostate hyperplasia, with PFNA having the highest impact followed by PFOS. These findings suggest that elevated serum levels of PFDeA, PFOA, PFOS, and PFNA are linked to prostate hyperplasia. Therefore, this study utilized advanced machine learning techniques to uncover potential hazardous effects of PFAS exposure on prostate health, specifically the positive association between PFAS and prostate hyperplasia.

Sulfonamide Per- and Polyfluoroalkyl Substances Can Impact Microorganisms Used in Aromatic Hydrocarbon and Trichloroethene Bioremediation.

Per- and polyfluoroalkyl substances (PFASs) from aqueous film forming foams (AFFFs) can hinder bioremediation of co-contaminants such as trichloroethene (TCE) and benzene, toluene, ethylbenzene, and xylene (BTEX). Anaerobic dechlorination can require bioaugmentation of Dehalococcoides, and for BTEX, oxygen is often sparged to stimulate in situ aerobic biodegradation. We tested PFAS inhibition to TCE and BTEX bioremediation by exposing an anaerobic TCE-dechlorinating coculture, an aerobic BTEX-degrading enrichment culture, and an anaerobic toluene-degrading enrichment culture to n-dimethyl perfluorohexane sulfonamido amine (AmPr-FHxSA), perfluorohexane sulfonamide (FHxSA), perfluorohexanesulfonic acid (PFHxS), or nonfluorinated surfactant sodium dodecyl sulfate (SDS). The anaerobic TCE-dechlorinating coculture was resistant to individual PFAS exposures but was inhibited by >1000× diluted AFFF. FHxSA and AmPr-FHxSA inhibited the aerobic BTEX-degrading enrichment. The anaerobic toluene-degrading enrichment was not inhibited by AFFF or individual PFASs. Increases in amino acids in the anaerobic TCE-dechlorinating coculture compared to the control indicated stress response, whereas the BTEX culture exhibited lower concentrations of all amino acids upon exposure to most surfactants (both fluorinated and nonfluorinated) compared to the control. These data suggest the main mechanisms of microbial toxicity are related to interactions with cell membrane synthesis as well as protein stress signaling.

Safe and sustainable fish and seafood system and per- and poly-fluorinated substances occurrence: the role of PFAS toxicity in the assessment.

Fish and seafood are valuable sources of both nutrients and organic contaminants. The expansion of the analytical per- and polyfluoroalkyl substances (PFAS) panel with toxicological characterisation necessitates an update of PFAS intake assessment and management within the context of cumulative exposure. Benthic and demersal seafood, such as clams, squid, and cuttlefish, are more prone to contamination with C9-C14 perfluorocarboxylic acids, exhibiting the highest relative potency factors in terms of immunotoxicity, according to the grid recently proposed by the European Commission Scientific Committee on Health, Environment, and Emerging Risk. Based on the Italian food consumption database referring to demersal and benthic biota such as squid, cuttlefish, crustaceans, and clams, a toxicology-based intake scenario was drafted to highlight the relevant contribution of such wild species to PFAS intake, well above the provisional health-based guidance value of 4.4ng/kg body weight per week. Ensuring consistency between PFAS reduction and substitution policies, environmental quality standards for water bodies, and the issuance of advisories and regulations regarding safe and sustainable intake of fish and seafood is crucial. This is done to prevent a loss of accountability for institutional bodies, which aim to protect fragile (sensitive and vulnerable) groups from PFAS exposure and simultaneously promote 'blue growth' as a sustainable food production system.

Associations between per- and polyfluoroalkyl chemicals and abdominal aortic calcification in middle-aged and older adults

IntroductionPer- and polyfluoroalkyl substances (PFAS) have infiltrated countless everyday products, raising concerns about potential effects on human health, specifically on the cardiovascular system and the development of abdominal aortic calcification (AAC). However, our understanding of this relationship is still limited. ObjectivesThis study aims to investigate the effects of PFAS on AAC using machine learning algorithms. MethodsLeveraging the power of machine learning (ML) technique, extreme gradient boosting (XGBoost), we assessed the relationship between PFAS exposure and AAC risk. We focused on three PFAS compounds, perfluorodecanoic acid (PFDeA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) through multiple logistic regression, restricted cubic spline (RCS), and quantile g-computation (QGC) models. To get more insight into the underlying mechanisms, mediation analyses are used to investigate the potential mediating role of fatty acids and blood cell fractions in AAC. ResultsOur findings indicate that elevated serum levels of PFHxS and PFDeA are associated with the increased risk of AAC. The QGC analyses underscore the overall positive association between the PFAS mixture and AAC risk, with PFHxS carrying the greatest weight, followed by PFDeA. The RCS analyses reveal a dose-dependent increase between serum PFHxS concentration and AAC risk in an inverted V-shape way. Moreover, age and PFHxS exposure are identified as the primary factors contributing to abdominal aortic calcification risk in SHapley Additive exPlanation (SHAP) summary plot combined with XGBoost technique. Although PFAS significantly change the profile of fatty acids, we do not find any mediating roles of them in AAC. Despite strong associations between PFAS exposure and hematological indicators, our analysis does not find evidence that these indicators mediate the development of AAC. ConclusionsIn summary, our study highlights the detrimental impact of PFAS on abdominal aortic health and emphasizes the need for further research to understand the underlying mechanisms involved.

Early-life exposure to per- and polyfluoroalkyl substances: Analysis of levels, health risk and binding abilities to transport proteins

Per- and polyfluoroalkyl substances (PFAS) can pass through the placenta and adversely affect fetal development. However, there is a lack of comparison of legacy and emerging PFAS levels among different biosamples in pregnant women and their offspring. This study, based on the Shanghai Maternal-Child Pairs Cohort, analyzed the concentrations of 16 PFAS in the maternal serum, cord serum, and breast milk samples from 1,076 mother-child pairs. The placental and breastfeeding transfer efficiencies of PFAS were determined in maternal-cord and maternal-milk pairs, respectively. The binding affinities of PFAS to five transporters were simulated using molecular docking. The results suggested that PFAS were frequently detected in different biosamples. The median concentration of perfluorooctane sulfonate (PFOS) was the highest at 8.85 ng/mL, followed by perfluorooctanoic acid (PFOA) at 7.13 ng/mL and 6:2 chlorinated polyfluorinated ether sulfonate at 5.59 ng/mL in maternal serum. The median concentrations of PFOA were highest in cord serum (4.23 ng/mL) and breast milk (1.08 ng/mL). PFAS demonstrated higher placental than breastfeeding transfer efficiencies. The transfer efficiencies and the binding affinities of most PFAS to proteins exhibited alkyl chain length-dependent patterns. Furthermore, we comprehensively assessed the estimated daily intakes (EDIs) of PFAS in breastfeeding infants of different age groups and used the hazard quotient (HQ) to characterize the potential health risk. EDIs decreased with infant age, and PFOS had higher HQs than PFOA. These findings highlight the significance of considering PFAS exposure, transfer mechanism, and health risks resulting from breast milk intake in early life.

Association of diet with per- and polyfluoroalkyl substances in plasma and human milk in the New Hampshire Birth Cohort Study

Per- and polyfluoroalkyl substances (PFAS) are related to various adverse health outcomes, and food is a common source of PFAS exposure. Dietary sources of PFAS have not been adequately explored among U.S. pregnant individuals. We examined associations of dietary factors during pregnancy with PFAS concentrations in maternal plasma and human milk in the New Hampshire Birth Cohort Study. PFAS concentrations, including perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), and perfluorodecanoate (PFDA), were measured in maternal plasma collected at ~28 gestational weeks and human milk collected at ~6 postpartum weeks. Sociodemographic, lifestyle and reproductive factors were collected from prenatal questionnaires and diet from food frequency questionnaires at ~28 gestational weeks. We used adaptive elastic net (AENET) to identify important dietary variables for PFAS concentrations. We used multivariable linear regression to assess associations of dietary variables selected by AENET models with PFAS concentrations. Models were adjusted for sociodemographic, lifestyle, and reproductive factors, as well as gestational week of blood sample collection (plasma PFAS), postpartum week of milk sample collection (milk PFAS), and enrollment year. A higher intake of fish/seafood, eggs, coffee, or white rice during pregnancy was associated with higher plasma or milk PFAS concentrations. For example, every 1 standard deviation (SD) servings/day increase in egg intake during pregnancy was associated with 4.4 % (95 % CI: 0.6, 8.4), 3.3 % (0.1, 6.7), and 10.3 % (5.6, 15.2) higher plasma PFOS, PFOA, and PFDA concentrations respectively. Similarly, every 1 SD servings/day increase in white rice intake during pregnancy was associated with 7.5 % (95 % CI: −0.2, 15.8) and 12.4 % (4.8, 20.5) greater milk PFOS and PFOA concentrations, respectively. Our study suggests that certain dietary factors during pregnancy may contribute to higher PFAS concentrations in maternal plasma and human milk, which could inform interventions to reduce PFAS exposure for both birthing people and offspring.

Cross-Sectional Associations between Prenatal Per- and Poly-Fluoroalkyl Substances and Bioactive Lipids in Three Environmental Influences on Child Health Outcomes (ECHO) Cohorts.

Prenatal per- and poly-fluoroalkyl substances (PFAS) exposure may influence gestational outcomes through bioactive lipids─metabolic and inflammation pathway indicators. We estimated associations between prenatal PFAS exposure and bioactive lipids, measuring 12 serum PFAS and 50 plasma bioactive lipids in 414 pregnant women (median 17.4 weeks' gestation) from three Environmental influences on Child Health Outcomes Program cohorts. Pairwise association estimates across cohorts were obtained through linear mixed models and meta-analysis, adjusting the former for false discovery rates. Associations between the PFAS mixture and bioactive lipids were estimated using quantile g-computation. Pairwise analyses revealed bioactive lipid levels associated with PFDeA, PFNA, PFOA, and PFUdA (p < 0.05) across three enzymatic pathways (cyclooxygenase, cytochrome p450, lipoxygenase) in at least one combined cohort analysis, and PFOA and PFUdA (q < 0.2) in one linear mixed model. The strongest signature revealed doubling in PFOA corresponding with PGD2 (cyclooxygenase pathway; +24.3%, 95% CI: 7.3-43.9%) in the combined cohort. Mixture analysis revealed nine positive associations across all pathways with the PFAS mixture, the strongest signature indicating a quartile increase in the PFAS mixture associated with PGD2 (+34%, 95% CI: 8-66%), primarily driven by PFOS. Bioactive lipids emerged as prenatal PFAS exposure biomarkers, deepening insights into PFAS' influence on pregnancy outcomes.

Setting PFAS-Based Fish Consumption Advisories for Virginia Waterways

This policy memo is intended for the Commissioner of Health at the Virginia Department of Health (VDH). The memo provides recommendations when assessing the need for per- and polyfluoroalkyl substances (PFAS)-based fish consumption advisories in Virginia waterways. High-frequency fish consumers and sensitive populations face a greater risk of negative health effects from exposure to PFAS through eating local freshwater fishes. By performing state-wide fish screening assessments for relevant PFAS, the VDH can determine if the nutritional benefits from eating fish outweigh the health risks from PFAS exposure. The following memo recommends that VDH update their PFAS fish tissue screening assessment to include PFUnA and PFDA and release final fish tissue screening recommendations for PFOA and PFOS.

Personal Strategies to Reduce the Cardiovascular Impacts of Environmental Exposures.

Ubiquitous environmental exposures increase cardiovascular disease risk via diverse mechanisms. This review examines personal strategies to minimize this risk. With regard to fine particulate air pollution exposure, evidence exists to recommend the use of portable air cleaners and avoidance of outdoor activity during periods of poor air quality. Other evidence may support physical activity, dietary modification, omega-3 fatty acid supplementation, and indoor and in-vehicle air conditioning as viable strategies to minimize adverse health effects. There is currently insufficient data to recommend specific personal approaches to reduce the adverse cardiovascular effects of noise pollution. Public health advisories for periods of extreme heat or cold should be observed, with limited evidence supporting a warm ambient home temperature and physical activity as strategies to limit the cardiovascular harms of temperature extremes. Perfluoroalkyl and polyfluoroalkyl substance exposure can be reduced by avoiding contact with perfluoroalkyl and polyfluoroalkyl substance-containing materials; blood or plasma donation and cholestyramine may reduce total body stores of perfluoroalkyl and polyfluoroalkyl substances. However, the cardiovascular impact of these interventions has not been examined. Limited utilization of pesticides and safe handling during use should be encouraged. Finally, vasculotoxic metal exposure can be decreased by using portable air cleaners, home water filtration, and awareness of potential contaminants in ground spices. Chelation therapy reduces physiological stores of vasculotoxic metals and may be effective for the secondary prevention of cardiovascular disease.

Associations between serum perfluoroalkyl and polyfluoroalkyl concentrations and diabetes mellitus in the Korean general population: Insights from the Korean National Environmental Health Survey 2018–2020

AimsRecent epidemiologic research has examined the relationship between perfluoroalkyl and polyfluoroalkyl substances (PFAS) and diabetes mellitus with inconclusive findings. In this cross-sectional study, we aimed to explore the association between serum PFAS concentrations and the prevalence of prediabetes and pre-diagnostic diabetes in the general Korean population as well as the combined effects of exposure to mixed PFAS compounds. MethodsWe analyzed data from participants aged ≥19 years enrolled in the Korean National Environmental Health Survey Cycle 4 (2018–2020). Individuals diagnosed with diabetes were excluded to minimize potential bias. We identified cases of pre-diagnostic diabetes based on the HbA1c level ≥6.5% and prediabetes as HbA1c levels of 5.7–6.49%. Serum concentrations of PFAS, including perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDeA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS), were quantified using high-performance liquid chromatography-tandem mass spectrometry. Survey-weighted logistic regression models were used to assess the relationships between PFAS levels and diabetes risk, adjusting for covariates. Additionally, Bayesian kernel machine regression (BKMR) was used to investigate the combined effects of exposure to mixed PFAS compounds. ResultsIn the study population excluding participants with diagnosed diabetes (n = 2709), the prevalence of pre-diagnostic diabetes and prediabetes was 4.8% and 30.1%, respectively. Significant positive associations were found between serum PFHxS and PFOS quartiles and pre-diagnostic diabetes risk. Likewise, among those without diagnosed or pre-diagnostic diabetes (n = 2579), the highest quartiles of PFDeA, PFHxS, and PFOS and the overall PFAS level were associated with an increased risk of prediabetes compared with the lowest quartiles. BKMR analysis revealed a significant positive association between overall serum PFAS level and prediabetes risk, which was most marked for PFOS. ConclusionsThese findings highlight the potential health implications of PFAS exposure and prediabetes risk. Further research is needed to validate these associations and identify potential mechanistic pathways.

Integration of ultrashort-chain compounds into the biomonitoring of per- and polyfluorinated substances in human plasma and serum

Ultrashort-chain (USC) per- and polyfluoroalkyl substances (PFAS) are small and very polar compounds with carbon chain lengths of shorter than C4. Their ubiquitous and high levels of occurrence in environmental aquatic systems have raised significant concern in conjunction with long-chain PFAS contamination. Measuring USC PFAS in blood can not only monitor human exposure but also serves as a valuable tool for studying the potential risks associated with USC PFAS exposure. The high polarity of USC PFAS poses a challenge to current analytical practices based on the reversed-phase liquid chromatography, primarily due to insufficient chromatographic retention. In this study, a simple and reliable workflow was developed for the simultaneous analysis of C1 to C10 perfluoroalkyl carboxylic and sulfonic acids, along with four alternative PFAS, in human plasma and serum. The chromatographic analysis was conducted using a polar-embedded reversed-phase LC column. Fetal bovine serum (FBS) was chosen for method validation due to its absence of all analytes, except for trifluoroacetic acid (TFA). Subsequently, a TFA isotope, 13C-TFA, was employed as a surrogate to assess the method accuracy for TFA in FBS. A single-step sample preparation procedure, conducted by mixing 100 µL of FBS with 200 µL of methanol, was demonstrated to be effective for the accurate and precise analysis of fortified FBS samples. Ten isotopes of C3 to C10 PFAS, serving as extracted internal standards, were added to the samples at 1 ppb to validate the accuracy of the entire workflow. Calibration standards were prepared in reverse osmosis water due to its cleanliness for all analytes. Phosphate-buffered saline was incorporated into the calibration standard solution to achieve similar chromatographic performance between standard and sample solutions. The calibration ranges varied among different analytes, spanning from 0.05 – 40 ppb, 0.1 – 40 ppb, 0.25 – 40 ppb, and 0.5 – 40 ppb. Method accuracy and precision were evaluated at three fortification levels, ranging from 0.4 to 30 ppb. All analytes and extracted internal standards exhibited recovery values within 20 % of the nominal concentration across all fortification levels. Satisfactory method precision was demonstrated with%RSD values <12 %. The validated method was applied to measure PFAS in NIST 1950 and 1957 standard reference human plasma and serum, affirming the established workflow is suitable for accurate quantification of C1 to C10 PFAS in human plasma and serum matrices.

Exposure to per- and polyfluoroalkyl substances in lung cancer patients and their associations with clinical health indicators

Per- and polyfluoroalkyl substances (PFASs) have potential carcinogenicity, immunotoxicity, and hepatotoxicity. Research has been conducted on PFAS exposure in people to discuss their potential health effects, excluding lung cancer. In this study, we recruited participants (n = 282) with lung cancer from Heilongjiang Province, northeast China. The PFAS concentrations were measured in their serum to fill the data gap of exposure, and relationships were explored in levels between PFASs and clinical indicators of tumor, immune and liver function. Ten PFASs were found in over 80 % of samples and their total concentrations were 5.27–152 ng/mL, with the highest level for perfluorooctanesulfonate (median: 12.4 ng/mL). Long-chain PFASs were the main congeners and their median concentration (20.5 ng/mL) was nearly three times to that of short-chain PFASs (7.61 ng/mL). Significantly higher concentrations of perfluorobutanoic acid, perfluorononanoic acid and perfluorohexanesulfonate were found in males than in females (p < 0.05). Serum levels of neuro-specific enolase were positively associated with perfluoropentanoic acid in all participants and were negatively associated with perfluorononanesulfonate in females (p < 0.05, multiple linear regression models). Exposure to PFAS mixture was significantly positively associated with the lymphocytic absolute value (difference: 0.224, 95% CI: 0.018, 0.470; p < 0.05, quantile g-computation models) and serum total bilirubin (difference: 2.177, 95% CI: 0.0335, 4.33; p < 0.05). Moreover, PFAS exposure can affect γ-glutamyl transpeptidase through several immune markers (p < 0.05, mediating test). Our results suggest that exposure to certain PFASs could interfere with clinical indicators in lung cancer patients. To our knowledge, this is the first study to detect serum PFAS occurrence and check their associations with clinical indicators in lung cancer patients.

All-cause, cardiovascular disease and cancer mortality in the population of a large Italian area contaminated by perfluoroalkyl and polyfluoroalkyl substances (1980–2018)

BackgroundPer- and polyfluoroalkyl substances (PFAS) are associated with many adverse health conditions. Among the main effects is carcinogenicity in humans, which deserves to be further clarified. An evident association has been reported for kidney cancer and testicular cancer. In 2013, a large episode of surface, ground and drinking water contamination with PFAS was uncovered in three provinces of the Veneto Region (northern Italy) involving 30 municipalities and a population of about 150,000. We report on the temporal evolution of all-cause mortality and selected cause-specific mortality by calendar period and birth cohort in the local population between 1980 and 2018.MethodsThe Italian National Institute of Health pre-processed and made available anonymous data from the Italian National Institute of Statistics death certificate archives for residents of the provinces of Vicenza, Padua and Verona (males, n = 29,629; females, n = 29,518) who died between 1980 and 2018. Calendar period analysis was done by calculating standardised mortality ratios using the total population of the three provinces in the same calendar period as reference. The birth cohort analysis was performed using 20–84 years cumulative standardised mortality ratios. Exposure was defined as being resident in one of the 30 municipalities of the Red area, where the aqueduct supplying drinking water was fed by the contaminated groundwater.ResultsDuring the 34 years between 1985 (assumed as beginning date of water contamination) and 2018 (last year of availability of cause-specific mortality data), in the resident population of the Red area we observed 51,621 deaths vs. 47,731 expected (age- and sex-SMR: 108; 90% CI: 107–109). We found evidence of raised mortality from cardiovascular disease (in particular, heart diseases and ischemic heart disease) and malignant neoplastic diseases, including kidney cancer and testicular cancer.ConclusionsFor the first time, an association of PFAS exposure with mortality from cardiovascular disease was formally demonstrated. The evidence regarding kidney cancer and testicular cancer is consistent with previously reported data.

Associations of per- and polyfluoroalkyl substances (PFAS) and their mixture with risk of rheumatoid arthritis in the U.S. adult population

BackgroundPer- and polyfluoroalkyl substances (PFAS) are known environmental contaminants with immunosuppressive properties. Their connection to rheumatoid arthritis (RA), a condition influenced by the immune system, is not well studied. This research explores the association between PFAS exposure and RA prevalence.MethodsThis research utilized data from the NHANES, encompassing a sample of 10,496 adults from the 2003–2018 cycles, focusing on serum levels of several PFAS. The presence of RA was determined based on self-reports. This study used multivariable logistic regression to assess the relationship between individual PFAS and RA risk, adjusting for covariates to calculate odds ratios (ORs). The combined effects of PFAS mixtures were evaluated using BKMR, WQS regression, and quantile g-computation. Additionally, sex-specific associations were explored through stratified analysis.ResultsHigher serum PFOA (OR = 0.88, 95% CI: 0.79, 0.98), PFHxS (OR = 0.91, 95% CI: 0.83, 1.00), PFNA (OR = 0.87, 95% CI: 0.77, 0.98), and PFDA (OR = 0.89, 95% CI: 0.81, 0.99) concentration was related to lower odds of RA. Sex-specific analysis in single chemical models indicated the significant inverse associations were only evident in females. BKMR did not show an obvious pattern of RA estimates across PFAS mixture. The outcomes of sex-stratified quantile g-computation demonstrated that an increase in PFAS mixture was associated with a decreased odds of RA in females (OR: 0.76, 95% CI: 0.62, 0.92). We identified a significant interaction term of the WQS*sex in the 100 repeated hold out WQS analysis. Notably, a higher concentration of the PFAS mixture was significantly associated with reduced odds of RA in females (mean OR = 0.93, 95% CI: 0.88, 0.98).ConclusionsThis study indicates potential sex-specific associations of exposure to various individual PFAS and their mixtures with RA. Notably, the observed inverse relationships were statistically significant in females but not in males. These findings contribute to the growing body of evidence indicating that PFAS may have immunosuppressive effects.

Association of Combined Per- and Polyfluoroalkyl Substances and Metals with Chronic Kidney Disease.

Background: Exposure to environmental pollutants such as metals and Per- and Polyfluoroalkyl Substances (PFAS) has become common and increasingly associated with a decrease in the estimated Glomerular Filtration Rate (eGFR), which is a marker often used to measure chronic kidney disease (CKD). However, there are limited studies involving the use of both eGFR and the urine albumin creatinine ratio (uACR), which are more comprehensive markers to determine the presence of CKD and the complexity of pollutant exposures and response interactions, especially for combined metals and PFAS, which has not been comprehensively elucidated. Objective: This study aims to assess the individual and combined effects of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), Cadmium (Cd), Mercury (Hg), and Lead (Pb) exposure on CKD using data from the National Health and Nutritional Examination Survey (NHANES) 2017-2018. Methods: We employed the use of bivariate logistic regression and Bayesian Kernel Machine Regression (BKMR) in our analysis of the data. Results: Logistic regression results revealed a positive association between PFOA and CKD. Our BKMR analysis revealed a non-linear and bi-phasic relationship between the metal exposures and CKD. In our univariate exposure-response function plot, Cd and Hg exhibited a U and N-shaped interaction, which indicated a non-linear and non-additive relationship with both low and high exposures associated with CKD. In addition, the bivariate exposure-response function between two exposures in a mixture revealed that Cd had a U-shaped relationship with CKD at different quantiles of Pb, Hg, PFOA, and PFOS, indicating that both low and high levels of Cd is associated with CKD, implying a non-linear and complex biological interaction. Hg's interaction plot demonstrated a N-shaped association across all quantiles of Cd, with the 75th quantile of Pb and the 50th and 75th quantiles of PFOA and PFOS. Furthermore, the PIP results underscored Cd's consistent association with CKD (PIP = 1.000) followed by Hg's (PIP = 0.9984), then PFOA and PFOS with a closely related PIP of 0.7880 and 0.7604, respectively, and finally Pb (PIP = 0.6940), contributing the least among the five environmental pollutants on CKD, though significant. Conclusions: Our findings revealed that exposure to environmental pollutants, particularly Hg and Cd, are associated with CKD. These findings highlight the need for public health interventions and strategies to mitigate the cumulative effect of PFAS and metal exposure and elucidate the significance of utilizing advanced statistical methods and tools to understand the impact of environmental pollutants on human health. Further research is needed to understand the mechanistic pathways of PFAS and metal-induced kidney injury and CKD, and longitudinal studies are required to ascertain the long-term impact of these environmental exposures.

Association of exposure to multiple perfluoroalkyl and polyfluoroalkyl substances and glucose metabolism in National Health and Nutrition Examination Survey 2017-2018.

To investigate the relationships between perfluoroalkyl and polyfluoroalkyl substances (PFASs) exposure and glucose metabolism indices. Data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 waves were used. A total of 611 participants with information on serum PFASs (perfluorononanoic acid (PFNA); perfluorooctanoic acid (PFOA); perfluoroundecanoic acid (PFUA); perfluorohexane sulfonic acid (PFHxS); perfluorooctane sulfonates acid (PFOS); perfluorodecanoic acid (PFDeA)), glucose metabolism indices (fasting plasma glucose (FPG), homeostasis model assessment for insulin resistance (HOMA-IR) and insulin) as well as selected covariates were included. We used cluster analysis to categorize the participants into three exposure subgroups and compared glucose metabolism index levels between the subgroups. Least absolute shrinkage and selection operator (LASSO), multiple linear regression analysis and Bayesian kernel machine regression (BKMR) were used to assess the effects of single and mixed PFASs exposures and glucose metabolism. The cluster analysis results revealed overlapping exposure types among people with higher PFASs exposure. As the level of PFAS exposure increased, FPG level showed an upward linear trend (p < 0.001), whereas insulin levels demonstrated a downward linear trend (p = 0.012). LASSO and multiple linear regression analysis showed that PFNA and FPG had a positive relationship (>50 years-old group: β = 0.059, p < 0.001). PFOA, PFUA, and PFHxS (≤50 years-old group: insulin β = -0.194, p < 0.001, HOMA-IR β = -0.132, p = 0.020) showed negative correlation with HOMA-IR/insulin. PFNA (>50 years-old group: insulin β = 0.191, p = 0.018, HOMA-IR β = 0.220, p = 0.013) showed positive correlation with HOMA-IR/insulin, which was essentially the same as results that obtained for the univariate exposure-response map in the BKMR model. Association of exposure to PFASs on glucose metabolism indices showed positive interactions between PFOS and PFHxS and negative interactions between PFOA and PFNA/PFOS/PFHxS. Our study provides evidence that positive and negative correlations between PFASs and FPG and HOMA-IR/insulin levels are observed, respectively. Combined effects and interactions between PFASs. Given the higher risk of glucose metabolism associated with elevated levels of PFAS, future studies are needed to explore the potential underlying mechanisms.

Estimating the dynamic early life exposure to PFOA and PFOS of the HELIX children: Emerging profiles via prenatal exposure, breastfeeding, and diet

In utero and children’s exposure to per- and polyfluoroalkyl substances (PFAS) is a major concern in health risk assessment as early life exposures are suspected to induce adverse health effects. Our work aims to estimate children’s exposure (from birth to 12 years old) to PFOA and PFOS, using a Physiologically-Based Pharmacokinetic (PBPK) modelling approach.A model for PFAS was updated to simulate the internal PFAS exposures during the in utero life and childhood, and including individual characteristics and exposure scenarios (e.g., duration of breastfeeding, weight at birth, etc.). Our approach was applied to the HELIX cohort, involving 1,239 mother–child pairs with measured PFOA and PFOS plasma concentrations at two sampling times: maternal and child plasma concentrations (6 to 12 y.o).Our model predicted an increase in plasma concentrations during fetal development and childhood until 2 y.o when the maximum concentrations were reached. Higher plasma concentrations of PFOA than PFOS were predicted until 2 y.o, and then PFOS concentrations gradually became higher than PFOA concentrations. From 2 to 8 y.o, mean concentrations decreased from 3.1 to 1.88 µg/L or ng/mL (PFOA) and from 4.77 to 3.56 µg/L (PFOS). The concentration–time profiles vary with the age and were mostly influenced by in utero exposure (on the first 4 months after birth), breastfeeding (from 5 months to 2 (PFOA) or 5 (PFOS) y.o of the children), and food intake (after 3 (PFOA) or 6 (PFOS) y.o of the children). Similar measured biomarker levels can correspond to large differences in the simulated internal exposures, highlighting the importance to investigate the children’s exposure over the early life to improve exposure classification.Our approach demonstrates the possibility to simulate individual internal exposures using PBPK models when measured biomarkers are scarce, helping risk assessors in gaining insight into internal exposure during critical windows, such as early life.

Bioaccumulation and trophic transfer of per- and polyfluoroalkyl substances in a subtropical mangrove estuary food web

Mangrove estuaries are an important land-sea transitional ecosystem that is currently under various pollution pressures, while there is a lack of research on per- and polyfluoroalkyl substances (PFAS) in the organisms of mangrove estuaries. In this study, we investigated the distribution and seasonal variation of PFAS in the tissues of organisms from a mangrove estuary. The PFAS concentrations in fish tissues varied from 0.45 ng/g ww to 17.67 ng/g ww and followed the order of viscera > head > carcass > muscle, with the highest tissue burden found in the fish carcass (39.59 ng). The log BAF values of PFDoDA, PFUnDA, and PFDA in the whole fish exceeded 3.70, indicating significant bioaccumulation. The trophic transfer of PFAS in the mangrove estuary food web showed a dilution effect, which was mainly influenced by the spatial heterogeneity of PFAS distribution in the estuarine environment, and demonstrated that the gradient dilution of PFAS in the estuary habitat environment can disguise the PFAS bio-magnification in estuarine organisms, and the larger the swimming ranges of organisms, the more pronounced the bio-dilution effect. The PFOA-equivalent HRs of category A and B fish were 3.48–5.17 and 2.59–4.01, respectively, indicating that mangrove estuarine residents had a high PFAS exposure risk through the intake of estuarine fish.