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CONTEXT: Evidence suggests that exposure to per- and polyfluoroalkyl substances (PFAS) increases the risk of developing cardiometabolic disease risk factors. Limited research has evaluated associations between PFAS, assessed during pregnancy, a sensitive window for maternal endocrine effects, and long-term maternal adiposity. OBJECTIVE: Estimate associations of early pregnancy measures of individual PFAS, and PFAS mixtures, with maternal adiposity in midlife. METHODS: We studied 547 Project Viva participants with measures of early pregnancy (mean gestation 10.0 weeks; mean age 32.5 years) plasma concentrations of 6 PFAS and midlife adiposity outcomes (mean follow-up 17.7 years; mean age 50.7 years), including weight, waist circumference (WC), trunk fat mass (TFM), and total body fat mass (TBFM). We used linear regression and Bayesian Kernel Machine Regression (BKMR). RESULTS: Linear regression estimated higher midlife weight per doubling of perfluorooctane sulfonate (PFOS) (3.8 kg [95% CI: 1.6, 5.9]) and 2-(N-ethyl-perfluorooctane sulfonamido) acetate (2.3 kg [95% CI: 0.9, 3.7]). BKMR analyses of single PFAS plasma concentrations (comparing the 25th percentile concentration to the 75th percentile) showed a positive association between PFOS and midlife adiposity (weight: 7.7 kg [95% CI: 4.0, 11.5]; TFM: 1.2 kg [95% CI: 0.0, 2.3]; TBFM: 3.0 kg [95% CI: 0.8, 5.2]), but inverse associations with perfluorononanoate (weight: -6.0 kg [95% CI: -8.5, -3.5]; WC: -1.8 cm [95% CI: -3.2, -0.3]; TFM: -0.8 kg [95% CI: -1.5, -0.1]; TBFM: -1.4 kg [95% CI: -2.7, -0.3]) and perfluorohexane sulfonate (TFM: -0.8 kg [95% CI: -1.5, -0.1]; TBFM: -1.4 kg [95% CI: -2.6, -0.2]). No associations were observed with the overall PFAS mixture. CONCLUSION: Select PFAS, assessed in pregnancy, may differentially affect maternal midlife adiposity, influencing later-life maternal cardiometabolic health.

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Short-chain perfluoroalkyl substances (PFAS) have been found to be relatively high in water treatment systems compared to long-chain PFAS because of the unsatisfactory adsorption efficiency of short-chain PFAS. Knowledge about why short-chain PFAS are less removed by porous carbon is very limited. The study focused on providing causal mechanisms that link the low adsorption of short-chain PFAS and proposing an improved method for removing both short- and long-chain PFAS. The long-chain PFAS with higher hydrophobicity diffused more quickly than the short-chain PFAS due to stronger partitioning driving forces. In the initial adsorption stage, therefore, pores of activated carbon were blocked by long-chain PFAS, which makes it difficult for the short-chain PFAS to enter the internal pores. Although several short-chain PFAS diffuse into the pores, the relatively more hydrophilic short-chain congeners cannot be fully adsorbed on activated carbon due to limited positively charged sites. Moreover, compared to larger particle sizes, smaller activated carbon particles have shorter pore channels near the surface, reducing the risk of pore-blocking and ensuring the pores remain accessible for more efficient adsorption. Additionally, these smaller particles offer a greater external surface area and more functional groups, which enhance the adsorption capacity. It indicates that the smaller particle size of activated carbon would have a positive effect on the short-chain PFAS removal.

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Although microplastics (MPs) and per- and polyfluoroalkyl substances (PFAS) have received tremendous attention separately, understanding their ubiquitous presence in the environment, persistence and toxicity requires comprehensive study of the fate and transport of co-existing MPs and PFAS. MPs may have large sorption capacity and can serve as vectors for PFAS to undergo long-range transport in water. Atmospheric deposition of both PFAS and MPs has been reported in urban, rural, and remote areas. This review identifies types and levels of PFAS and MPs in air, their interactions, and environmental factors contributing to their air-water deposition. MPs in combination with PFAS may carry combined toxicity and pose elevated risks to ecosystems and human health. Our review shows that air-water deposition of MPs and PFAS can be governed by environmental factors including precipitation, humidity, UV, wind, and particulate matter levels in the air. Increasing humidity may increase MP particle size due to hygroscopic growth, which affects its distribution and deposition rate. Humidity has been observed to have both positive and negative impacts on PFAS partitioning onto MPs. More attention should be paid to MPs and PFAS co-occurrence when addressing their transport behavior in air and deposition to aquatic systems.

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The analysis of per- and polyfluoroalkyl substances (PFAS) via sum parameters like extractable organic fluorine (EOF) in combination with high resolution-continuum source-graphite furnace molecular absorption spectrometry (HR-CS-GFMAS) is highly promising regarding fluorine sensitivity and selectivity. However, the HR-CS-GFMAS method includes several drying and heating steps which can lead to losses of volatile PFAS before the molecular formation step using e.g., GaF formation. Hence, the method leads to a strong discrimination of PFAS within the EOF depending on their physical/chemical properties and is therefore associated with reduced accuracy. To reduce this discrepancy and to indicate realistic PFAS pollution values, an optimization of the HR-CS-GFMAS method for PFAS analysis is needed. Hence, we determined fluorine response factors of several PFAS with different physical/chemical properties upon application of systematic optimization steps. We could therefore improve the method's sensitivity for PFAS analysis using a modifier drying pre-treatment step followed by a sequential injection of sample solutions. The highest improvement in sensitivity of volatile PFAS was shown upon addition of a Mg modifier during drying pre-treatment. Thereby, during optimization the relative standard deviation of fluorine response factors could be reduced from 55 % (initial method) to 27 % (optimized method) leading to a more accurate determination of organofluorine sum parameters. The method provides an instrumental LOD and LOQ of ß(F) 1.71 µg/L and 5.13 µg/L, respectively. Further validation aimed to investigate several matrix effects with respect to water matrices. Here, substance-specific behavior was observed. For example, perfluorooctanoic acid (PFOA) which was used as calibrator, showed signal suppressions upon high chloride concentrations (>50 mg/L). Hence, a thorough separation of Cl from analytes during sample preparation is needed for accurate sum parameter analysis.

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Contrary to the initial hypothesis, Flemish adolescents who reported consuming organic food at least 7.5 times per week did not exhibit reduced internal exposure to the tested recently used pesticides. After adjustment for gender, age, country of origin, socioeconomic status, body mass index, consumption of high-fat foods and foods linked to organic food consumption, and concerning organochlorine derivatives and lead, additional adjustment for the duration of breastfeeding expressed in weeks, they displayed slightly elevated internal exposure to organochlorine derivatives, lead, methyl arsenate, and toxic relevant arsenic. A comparison was also made between the correlation of internal exposure to pollutants with the frequency of organic food consumption on one hand and the total consumption of equivalent products from all sources on the other. Regarding potatoes, vegetables, and fruits, no clear trends were observed. Regarding eggs, there was a trend towards higher internal exposures with organic food consumption, significant for trans-nonachlor, PCB118, and 2,4-dichlorophenoxyacetic acid, and marginally significant for glyphosate. For dairy, there was a trend towards higher internal exposures with organic food consumption, significant for perfluorononanoic acid and marginally significant for PCB153. Regarding nuts and seeds, the higher internal exposure to dichlorophenoxyacetic acid and the lower exposure to 3-phenoxybenzoic acid were marginally significant, while there was also a trend towards higher internal exposure to other pollutants with organic food consumption, significant for PCB118, PCB153, and sum PCBs, and marginally significant for trans-nonachlor. Concerning breakfast cereals and muesli, no clear trends were observed.

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In recent years, there has been a notable surge in environmental incidents, including wildfires and chemical releases. Responses to such events have primarily focused on addressing acute and immediate impacts. However, potential long-term health risks have been overlooked. Our proposed framework first advocates for the holistic identification of contaminants, prioritizing persistent organic contaminants determined through both knowledge-based and non-targeted and targeted analysis. We suggest integrating environmental monitoring and modeling approaches to assess the extent and composition of contamination caused by these chemicals. To facilitate swift assessments, we advocate the development of streamlined chemical analysis techniques and dedicated technologies for in situ monitoring of persistent organic chemicals. In addition, we provide an overview of both traditional and state-of-the-art approaches to risk assessment and introduce a three-tier risk assessment framework for evaluating the long-term health risks associated with environmental incidents. We emphasize the importance of in situ soil remediation and coordinated recovery efforts, including effective communication, evacuation, and cleaning plans for affected spaces, which are pivotal for facilitating recovery from environmental incidents. This comprehensive approach fortifies preparedness and recovery strategies, providing a robust framework for managing future environmental crises.

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Per- and polyfluoroalkyl substances (PFAS) represent a class of persistent synthetic chemicals extensively utilized across industrial and consumer sectors, raising substantial environmental and human health concerns. Epidemiological investigations have robustly linked PFAS exposure to a spectrum of adverse health outcomes. Altered metabolites stand as promising biomarkers, offering insights into the identification of specific environmental pollutants and their deleterious impacts on human health. However, elucidating metabolic alterations attributable to PFAS exposure and their ensuing health effects has remained challenging. In light of this, this review aims to elucidate potential biomarkers of PFAS exposure by presenting a comprehensive overview of recent metabolomics-based studies exploring PFAS toxicity. Details of PFAS types, sources, and human exposure patterns are provided. Furthermore, insights into PFAS-induced liver toxicity, reproductive and developmental toxicity, cardiovascular toxicity, glucose homeostasis disruption, kidney toxicity, and carcinogenesis are synthesized. Additionally, a thorough examination of studies utilizing metabolomics to delineate PFAS exposure and toxicity biomarkers across blood, liver, and urine specimens is presented. This review endeavors to advance our understanding of PFAS biomarkers regarding exposure and associated toxicological effects.

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Per- and polyfluoroalkyl substances (PFAS), ubiquitous in a myriad of consumer and industrial products, and depending on the doses of exposure represent a hazard to both environmental and public health, owing to their persistent, mobile, and bio accumulative properties. These substances exhibit long half-lives in humans and can induce potential immunotoxic effects at low exposure levels, sparking growing concerns. While the European Food Safety Authority (EFSA) has assessed the risk to human health related to the presence of PFAS in food, in which a reduced antibody response to vaccination in infants was considered as the most critical human health effect, a comprehensive grasp of the molecular mechanisms spearheading PFAS-induced immunotoxicity is yet to be attained. Leveraging modern computational tools, including the Agent-Based Model (ABM) Universal Immune System Simulator (UISS) and Physiologically Based Kinetic (PBK) models, a deeper insight into the complex mechanisms of PFAS was sought. The adapted UISS serves as a vital tool in chemical risk assessments, simulating the host immune system's reactions to diverse stimuli and monitoring biological entities within specific adverse health contexts. In tandem, PBK models unravelling PFAS' biokinetics within the body i.e. absorption, distribution, metabolism, and elimination, facilitating the development of time-concentration profiles from birth to 75 years at varied dosage levels, thereby enhancing UISS-TOX's predictive abilities. The integrated use of these computational frameworks shows promises in leveraging new scientific evidence to support risk assessments of PFAS. This innovative approach not only allowed to bridge existing data gaps but also unveiled complex mechanisms and the identification of unanticipated dynamics, potentially guiding more informed risk assessments, regulatory decisions, and associated risk mitigations measures for the future.

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The detection of the highly toxic per- and polyfluoroalkyl substances, PFAS, constitutes a challenging task in terms of developing a generic method that could be rapid and applicable simultaneously to both long and short-chain PFAS at ppt concentration level. In the present study, the method introduced by the USA Environmental Protection Agency, EPA, to detect surfactants, using methylene blue, MB, which is identified an ideal candidate for PFAS-MB ion pairing, is extended at the lowest concentration range by a simple additional step that involves the dissociation of the ion pairs in water. In this work, Surface Enhanced Raman Scattering, SERS, is applied via Ag nanocolloidal suspensions to probe MB and indirectly either/or both short-chain (perfluorobutyric acid, PFBA) and long-chain (perfluoloctanoic acid, PFOA) PFAS downt to 5 ppt. This method, which can be further optimized to sub-ppt level via a custom-made SERS-PFAS dedicated Raman system, offers the possibility to be applied to either specific PFAS (both short and long-chain) in a targeted analysis or to total PFAS in a non-targeted analysis at very low detection limits, following any type of MB detection method in aqueous solutions and obviously with any type of SERS substrate.

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Per- and Polyfluoroalkyl substances (PFAS) are a group of persistent long-lived chemicals with global environmental contamination. The published literature is rife with confusing and sometimes contradictory effects of PFAS on animal and cell models, as well as epidemiological studies. Cytotoxicity studies are often used as an early indicator to guide safety requirements, regulation, and further studies and thus can be useful to understand important toxicity differences by various PFAS. Recent studies have found that PFAS are not equivalently toxic on all cell types, and that not all cell types exhibit the same sensitivity to individual PFAS. However, immune cells have not been well studied. As immune cells are important for regulating responses to environmental toxins, infection, and cancer, we sought to discover the sensitivity of these cells to various PFAS, including legacy and replacement compounds. We assessed a range of concentrations and found that immune cells are generally more robust when exposed to PFAS, and that Jurkat T-cells were more sensitive than THP-1 monocytes. As monocytes are critical for coordinating inflammatory responses to external threats with cell death cascades, we further investigated these cells. We discovered that THP-1 cells do not undergo organized or programmed death, such as apoptosis or pyroptosis, and instead PFAS exposure results in a more necrotic/lytic and unorganized death, likely contributing to potential inflammatory effects downstream.

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Known as "forever chemicals", per- and polyfluoroalkyl substances (PFAS) are synthetic compounds used in consumer goods but pose significant public health concerns, including disruption of the thyroid system. As thyroid hormones (THs) are required for normal brain development, PFAS may also be developmental neurotoxicants. However, this is not well understood. Here we examine the endocrine and neurodevelopmental consequences of perfluorohexane sulfonate (PFHxS) exposure in pregnant, lactating, and developing rats, and compare its effects to an anti-thyroid pharmaceutical (propylthiouracil, PTU) that induces thyroid-mediated developmental neurotoxicity. We show that PFHxS dramatically reduces maternal serum thyroxine (T4), nearly equivalently to PTU (-55 and -51%, respectively). However, only PTU increases thyroid stimulating hormone. The lactational transfer of PFHxS is significant and reduces pup serum T4 across the postnatal period. Surprisingly, brain THs are only minimally decreased by PFHxS, whereas PTU drastically diminishes them. Evaluation of brain TH action by phenotyping, RNA-Sequencing, and quantification of radial glia cell morphology supports that PTU interrupts TH signaling while PFHxS has limited to no effect. These data show that PFHxS induces abnormal serum TH profiles; however, there were no indications of hypothyroidism in the postnatal brain. We suggest the stark differences between the neurodevelopmental effects of PFHxS and a typical antithyroid agent may be due to its interaction with TH distributing proteins like transthyretin.

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Improved treatment of per- and polyfluoroalkyl substances (PFAS) in water is critically important in light of the proposed United States Environmental Protection Agency (USEPA) drinking water regulations at ng L-1 levels. The addition of peroxymonosulfate (PMS) during electrooxidation (EO) can remove and destroy PFAS, but ng L-1 levels have not been tested, and PMS itself can be toxic. The objective of this research was to test peroxydisulfate (PDS, an alternative to PMS) activation by boron-doped diamond (BDD) electrodes for perfluorooctanoic acid (PFOA) degradation. The influence of PDS concentration, temperature, and environmental water matrix effects, and PFOA concentration on PDS-EO performance were systematically examined. Batch reactor experiments revealed that 99 % of PFOA was degraded and 69 % defluorination was achieved, confirming PFOA mineralization. Scavenging experiments implied that sulfate radicals (SO4-) and hydroxyl radicals (HO) played a more important role for PFOA degradation than 1O2 or electrons (e-). Further identification of PFOA degradation and transformation products by liquid chromatography-mass spectrometry (LC-MS) analysis established plausible PFOA degradation pathways. The analysis corroborates that direct electron transfers at the electrode initiate PFOA oxidation and SO4- improves overall treatment by cleaving the CC bond between the C7F15 and COOH moieties in PFOA, leading to possible products such as C7F15 and F-. The perfluoroalkyl radicals can be oxidized by SO4- and HO, resulting in the formation of shorter chain perfluorocarboxylic acids (e.g., perfluorobutanoic acid [PFBA]), with eventual mineralization to CO2 and F-. At an environmentally relevant low initial concentration of 100 ng L-1 PFOA, 99 % degradation was achieved. The degradation of PFOA was slightly affected by the water matrix as less removal was observed in an environmental river water sample (91 %) compared to tests conducted in Milli-Q water (99 %). Overall, EO with PDS provided a destructive approach for the elimination of PFOA.

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Tightening of environmental regulations against long-chain perfluoroalkyl acids (PFAAs) since the 2000s may have led to significant increases in the occurrence of short-chain PFAAs in the environment. Understanding the impact of the regulations on composition of durable water repellents (DWRs) is imperative to guide implementation of pragmatic actions during their use and end-of-life treatment. Substantial decreases in the frequencies of detection and concentrations of long-chain PFAAs and long-chain PFAA-precursors, and substantial increases in those of short-chain PFAAs and short-chain PFAA-precursors, have been observed in the impurities and hydrolysis products of side-chain fluorinated polymers (SCFPs). Comparison of profiles among the DWRs containing fluorinated ingredients in 2011 indicated that DWRs containing C8F17- and C10F21-SCFPs were the dominant products and accounted for 90 % of the samples, whereas DWRs containing C4F9- and C6F13-SCFPs were the dominant products and accounted for 70 % of the samples collected in 2021. Tightening of the regulations have caused decreasing applications of long-chain SCFPs and increasing use of short-chain SCFPs in DWRs containing fluorinated ingredients. The ingredients of one DWR were changed from PFAS-free alternatives to short-chain SCFPs, whereas those of another DWR were changed from short-chain SCFPs to PFAS-free alternatives. The presence of unexplained extractable organic fluorine has been observed in DWRs containing fluorinated ingredients, which may be difficult to be hydrolyzed and form known compounds. A historical series of DWRs available from before and after the tightening of regulations and a multifaceted analytical technique consisting of combustion ion chromatographic and mass spectrometric approaches combined with two extraction techniques involving ultrasonic treatment and alkaline hydrolysis revealed the impact of tightening regulations on composition of DWRs.

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Per- and polyfluoroalkyl substances (PFAS) constitutes a group of highly persistent man-made substances. Recent evidence indicates that PFAS negatively impact the immune system. However, it remains unclear how different PFAS are associated with alterations in circulating leukocyte subpopulations. More detailed knowledge of such potential associations can provide better understanding into mechanisms of PFAS immunotoxicity in humans. In this exploratory study, associations of serum levels of common PFAS (perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS)) and immune cell profiles of peripheral blood mononuclear cells, both with and without immunostimulation, were investigated. High-dimensional single cell analysis by mass cytometry was done on blood leukocytes from fifty participants in the Norwegian human biomonitoring EuroMix study. Different PFAS were associated with changes in various subpopulations of natural killer (NK), T helper (Th), and cytotoxic T (Tc) cells. Broadly, PFAS concentrations were related to increased frequencies of NK cells and activated subpopulations of NK cells. Additionally, increased levels of activated T helper memory cell subpopulations point to Th2/Th17 and Treg-like skewed profiles. Finally, PFAS concentrations were associated with decreased frequencies of T cytotoxic cell subpopulations with CXCR3+ effector memory (EM) phenotypes. Several of these observations point to biologically plausible mechanisms that may contribute to explaining the epidemiological reports of immunosuppression by PFAS. Our results suggest that PFAS exposures even at relatively low levels are associated with changes in immune cell subpopulations, a finding which should be explored more thoroughly in a larger cohort. Additionally, causal relationships should be confirmed in experimental studies. Overall, this study demonstrates the strength of profiling by mass cytometry in revealing detailed changes in immune cells at a single cell level.

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Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are associated with adverse health effects. This study examined the trend of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) levels in individuals with and without pre-existing comorbidities. We analyzed the characteristics of 13,887 participants across nine U.S. NHANES cycles (1999-2000 to 2017-2018) and calculated the geometric mean (GM) of PFOA and PFOS levels, standardized by sex and age. A joinpoint regression model was used to analyze the temporal trends of serum PFOA and PFOS levels. We observed declining PFOA and PFOS serum levels among adults in NHANES from 1999-2000 to 2017-2018. Serum PFOA and PFOS concentrations were higher in men, smokers, and individuals with pre-existing CKD, hyperlipidemia, CVD, and cancer. We observed faster decline rates in PFOA levels among individuals with diabetes and CKD and faster decline rates in PFOS levels among individuals with diabetes and those without CKD. This study provided evidence of varying levels and changing trends of PFOA and PFOS between groups with and without established chronic disease, highlighting the role of environmental chemicals in the onset and development of chronic diseases.

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Globally implemented ecological risk assessment (ERA) guidelines marginalize hormesis, a biphasic dose-response relationship characterized by low-dose stimulation and high-dose inhibition. The present study illuminated the promise of hormesis as a scientific dose-response model for ERA of per- and polyfluoroalkyl substances (PFAS) represented by perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS). A total of 266 hormetic dose-response relationships were recompiled from 1237 observations, covering 30 species from nine representative taxonomic groups. The standardized hormetic amplitudes followed the log-normal probability distribution, being subject to the limits of biological plasticity but independent of stress inducers. The SHapley Additive exPlanations algorithm revealed that the target endpoint was the most important variable explaining the hormetic amplitudes. Subsequently, quantitative frameworks were established to incorporate hormesis into the predicted no-effect concentration levels, with a lower induction dose and a zero-equivalent point but a broader hormetic zone for PFOS. Realistically, 10,117 observed concentrations of PFOA and PFOS were gathered worldwide, 4% of which fell within hormetic zones, highlighting the environmental relevance of hormesis. Additionally, the hormesis induction potential was identified in other legacy and emerging PFAS as well as their alternatives and mixtures. Collectively, it is time to incorporate the hormesis concept into PFAS studies to facilitate more realistic risk characterizations.

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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.

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This review examines the extensive use and environmental consequences of Per- and Polyfluoroalkyl Substances (PFAS) on a global scale, specifically emphasizing their potential impact in Nigeria. Recognized for their resistance to water and oil, PFAS are under increased scrutiny for their persistent nature and possible ecotoxicological risks. Here, we consolidate existing knowledge on the ecological and human health effects of PFAS in Nigeria, focusing on their neurological effects and the risks they pose to immune system health. We seek to balance the advantages of PFAS with their potential ecological and health hazards, thereby enhancing understanding of PFAS management in Nigeria and advocating for more effective policy interventions and the creation of safer alternatives. The review concludes with several recommendations: strengthening regulatory frameworks, intensifying research into the ecological and health impacts of PFAS, developing new methodologies and longitudinal studies, fostering collaborative efforts for PFAS management, and promoting public awareness and education to support sustainable environmental practices and healthier communities in Nigeria.

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BACKGROUND: In the past, perfluorooctanoic acid (PFOA) was produced and applied as an emulsifier in a fluoropolymer production plant in the Altötting district, southern Bavaria (Germany). This chemical was released directly into the environment, resulting in the contamination of the local drinking water. During a human biomonitoring (HBM) survey in 2018, increased median PFOA blood serum levels, compared to a normally exposed control group with no known source of PFOA exposure from Munich, Germany, were detected in the resident population (23.18 µg/l in the general population, 20.71 µg/l in the children's group). The follow-up study aimed to investigate whether purification of the drinking water as the main PFOA exposure source has been successful in reducing internal PFOA exposure and to estimate the association of internal PFOA exposure with possible influencing factors. METHODS: Only individuals who had already participated in the HBM study in 2018 were included. For the determination of the PFOA serum concentration, 5 ml of blood was drawn from each participating person. Blood samples were collected in the period from June to August 2022. Furthermore, information on sociodemographic characteristics, health status, dietary behaviour and other lifestyle factors were collected by means of a self-administered questionnaire. To examine the association of PFOA blood serum levels with possible influencing factors, such as age, gender and consumption of fish and game meat, a logistic regression model with a PFOA value > 10 µg/l as outcome was used. RESULTS: A total of 764 individuals participated in the follow-up study in 2022. Analyses were performed separately for the general population (n = 559), women of reproductive age (15-49 years old) (n = 120), and children under 12 years old (n = 30). Median PFOA blood levels have decreased by 56.9% in the general population, by 59.8% in the group of women of reproductive age and by 73.4% in the group of children under 12 years old. In the general population, a higher probability of a PFOA value > 10 µg/l was found for those aged 40-59 years (Odds ratio (OR) = 2.33 (95%CI: 1.23 to 4.43, p = 0.01) and those aged 60 years and older (OR = 5.32, 95%CI: 2.78 to 10.19, p < 0.001). CONCLUSIONS: In all study groups, the median PFOA serum levels decreased as expected after a half-life of four years, which confirms that contamination via drinking water has ceased. Furthermore, our study identified age as a significant predictor of internal PFOA exposure, while no influence was found for the consumption of fish and game meat. Further investigations are needed to quantify in a more detailed way the influence of dietary habits on PFOA exposure.

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BACKGROUND: Evidence suggests that exposure to per- and polyfluoroalkyl substances (PFAS) increases risk of high blood pressure (BP) during pregnancy. Prior studies did not examine associations with BP trajectory parameters (i.e., overall magnitude and velocity) during pregnancy, which is linked to adverse pregnancy outcomes. OBJECTIVES: To estimate associations of multiple plasma PFAS in early pregnancy with BP trajectory parameters across the second and third trimesters. To assess potential effect modification by maternal age and parity. METHODS: In 1297 individuals, we quantified six PFAS in plasma collected during early pregnancy (median gestational age: 9.4 weeks). We abstracted from medical records systolic BP (SBP) and diastolic BP (DBP) measurements, recorded from 12 weeks gestation until delivery. BP trajectory parameters were estimated via Super Imposition by Translation and Rotation modeling. Subsequently, Bayesian Kernel Machine Regression (BKMR) was employed to estimate individual and joint associations of PFAS concentrations with trajectory parameters - adjusting for maternal age, race/ethnicity, pre-pregnancy body mass index, income, parity, smoking status, and seafood intake. We evaluated effect modification by age at enrollment and parity. RESULTS: We collected a median of 13 BP measurements per participant. In BKMR, higher concentration of perfluorooctane sulfonate (PFOS) was independently associated with higher magnitude of overall SBP and DBP trajectories (i.e., upward shift of trajectories) and faster SBP trajectory velocity, holding all other PFAS at their medians. In stratified BKMR analyses, participants with ≥ 1 live birth had more pronounced positive associations between PFOS and SBP velocity, DBP magnitude, and DBP velocity - compared to nulliparous participants. We did not observe significant associations between concentrations of the overall PFAS mixture and either magnitude or velocity of the BP trajectories. CONCLUSION: Early pregnancy plasma PFOS concentrations were associated with altered BP trajectory in pregnancy, which may impact future cardiovascular health of the mother.

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