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Per- and polyfluoroalkyl substances (PFASs) have been widely detected in various food, which has attracted worldwide concern. However, the factors influencing the transfer and bio-accumulation of PFASs from soils to wheat in normal farmland, is still ambiguous. We investigated the PFASs accumulation in agricultural soils and grains from 10 cites, China, and evaluated the health risks of PFASs via wheat consumption. Our results show that ∑PFASs in soils range from 0.34 μg/kg to 1.59 μg/kg with PFOA and PFOS dominating, whilst ∑PFASs in wheats range from 2.74 to 6.01 μg/kg with PFOA, PFBA and PFHxS dominating. The lower pH conditions and high total organic carbon (TOC) could result in the higher accumulation of PFASs in soils and subsequently in wheat grains, whilst the bioaccumulation factors of PFASs increase with increasing pH conditions but not with TOC. The estimated daily intake (EDI) values of PFBA, PFOA, and PFHxS are relatively high, but data supports that ingesting wheat grains does not result in any potential risk to the human beings. Our studies provided more information about PFASs accumulation in wheat grains, and help us understand the current potential risks of PFASs in food., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Per- and polyfluoroalkyl substances (PFAS) encompass a diverse group of synthetic fluorinated chemicals known to elicit adverse health effects in animals and humans. However, only a few studies investigated the mechanisms underlying clearance of PFAS. Herein, the relevance of human renal transporters and permeability to clearance and bioaccumulation for 14 PFAS containing three to eleven perfluorinated carbon atoms (η pfc  = 3-11) and several functional head-groups was investigated. Apparent permeabilities and interactions with human transporters were measured using in vitro cell-based assays, including the MDCK-LE cell line, and HEK293 stable transfected cell lines expressing organic anion transporter (OAT) 1-4 and organic cation transporter (OCT) 2. The results generated align with the Extended Clearance Classification System (ECCS), affirming that permeability, molecular weight, and ionization serve as robust predictors of clearance and renal transporter engagement. Notably, PFAS with low permeability (ECCS 3A and 3B) exhibited substantial substrate activity for OAT1 and OAT3, indicative of active renal secretion. Furthermore, we highlight the potential contribution of OAT4-mediated reabsorption to the renal clearance of PFAS with short η pfc , such as perfluorohexane sulfonate (PFHxS). Our data advance our mechanistic understanding of renal clearance of PFAS in humans, provide useful input parameters for toxicokinetic models, and have broad implications for toxicological evaluation and regulatory considerations., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier Ltd.)

Advances in biological degradation of per- and polyfluoroalkyl substances (PFAS) have shown that bioremediation is a promising method of PFAS mineralization; however, most of these studies focus on remediation of more reactive polyfluorinated compounds. This review focuses on the defluorination of the more recalcitrant perfluorinated alkyl acids (PFAAs) by bacteria. We highlight key studies that report PFAA degradation products, specific bacteria, and relevant genes. Among these studies, we discuss trends in anaerobic versus aerobic conditions with specific bacterial species or consortia. This holistic review seeks to elucidate the state of PFAA biodegradation research and discuss the need for future research for environmental application., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Per- and polyfluoroalkyl substances (PFAS), particularly the perfluorinated ones, are recalcitrant to biodegradation. By integrating an enrichment culture of reductive defluorination with biocompatible electrodes for the electrochemical process, a deeper defluorination of a C 6 -perfluorinated unsaturated PFAS was achieved compared to the biological or electrochemical system alone. Two synergies in the bioelectrochemical system were identified: i) The in-series microbial-electrochemical defluorination and ii) the electrochemically enabled microbial defluorination of intermediates. These synergies at the material-microbe interfaces surpassed the limitation of microbial defluorination and further turned the biotransformation end products into less fluorinated products, which could be less toxic and more biodegradable in the environment. This material-microbe hybrid system brings opportunities in the bioremediation of PFAS driven by renewable electricity and warrants future research on mechanistic understanding of defluorinating and electroactive microorganisms at the material-microbe interface for system optimizations., Competing Interests: Competing interests statement:The authors declare no competing interest.

Despite their significant impact, comprehensive screenings and detailed analyses of per- and polyfluoroalkyl substance (PFAS) binding strengths at the orthosteric and allosteric sites of NRs are currently lacking. This study addresses this gap by focusing on the binding interaction analysis of both common and uncommon PFAS with the nuclear receptors (NRs) vitamin D receptor (VDR), peroxisome proliferator-activated receptor gamma (PPARγ), pregnane X receptor (PXR), and estrogen receptor alpha (ERα). Advanced docking simulations were used to screen 9507 PFAS chemicals at the orthosteric and allosteric sites of PPARγ, PXR, VDR, and ERα. All receptors exhibited strong binding interactions at the orthosteric and allosteric site with a significant number of PFAS. We verified the accuracy of the docking protocol through multiple docking controls and validations. A mixture modeling analysis indicates that PFAS can bind in various combinations with themselves and endogenous ligands simultaneously, to disrupt the endocrine system and cause carcinogenic responses. These findings reveal that PFAS can interfere with nuclear receptor activity by displacing endogenous or native ligands by binding to the orthosteric and allosteric sites. The purpose of this study is to explore the mechanisms through which PFAS exert their endocrine-disrupting effects, potentially leading to more targeted therapeutic strategies. Importantly, this study is the first to explore the binding of PFAS at allosteric sites and to model PFAS mixtures at nuclear receptors. Given the high concentration and persistence of PFAS in humans, this study further emphasizes the urgent need for further research into the carcinogenic mechanisms of PFAS and the development of therapeutic strategies that target nuclear receptors.

Enzymatic cleavage of C─F bonds in per- and polyfluoroalkyl substances (PFAS) is largely unknown but avidly sought to promote systems biology for PFAS bioremediation. Here, we report the reductive defluorination of α, β-unsaturated per- and polyfluorocarboxylic acids by Acetobacterium spp. The microbial defluorination products were structurally confirmed and showed regiospecificity and stereospecificity, consistent with their formation by enzymatic reactions. A comparison of defluorination activities among several Acetobacterium species indicated that a functional fluoride exporter was required for the detoxification of the released fluoride. Results from both in vivo inhibition tests and in silico enzyme modeling suggested the involvement of enzymes of the flavin-based electron-bifurcating caffeate reduction pathway [caffeoyl-CoA reductase (CarABCDE)] in the reductive defluorination. This is a report on specific microorganisms carrying out enzymatic reductive defluorination of PFAS, which could be linked to electron-bifurcating reductases that are environmentally widespread.

The fate and distribution of environmental contaminants includes bioaccumulation within marine organisms. A deceased 4-m long adult female bluntnose sixgill shark, pregnant with 72 pups, was recovered from Coles Bay on Vancouver Island, BC, Canada in 2019. This specimen provided a unique opportunity to examine maternal transfer of contaminants in a yolk-sac viviparous shark species. Liver subsamples of the adult and offspring were analyzed for 18 targeted inorganic elements by inductively coupled plasma optical emission spectroscopy (ICP-OES) and 21 targeted perfluoroalkyl substances (PFAS) by liquid chromatography-electrospray ionization-high resolution mass spectrometry (LC-ESI-Orbitrap MS). The maternal-offspring transfer efficiencies in liver tissue were subsequently examined for both contaminant classes. Concentrations of all detectable metals apart from calcium and magnesium were found to be higher in the mother compared to the offspring, including substantial levels of toxic cadmium (6 ± 2 mg kg -1 dw) and lead (7 ± 3 mg kg -1 dw). Conversely, high maternal transfer efficiencies were observed for PFAS (i.e., ΣPFAS = 71 ± 9 ng g -1 ww in offspring compared to 13 ± 9 ng g -1 ww in the mother). This study highlighted the unique maternal transfer characteristics of PFAS in bluntnose sixgill sharks depending on the structure of the polar head group, with greater liver-to-liver transfer efficiencies observed for perfluorocarboxylic acids (PFCAs) than perfluorosulfonic acids (PFSAs) of the same fluorocarbon chain length., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

An increasing number of per- and polyfluoroalkyl substances (PFAS) exposed to the environment may pose a threat to organisms and human beings. However, there is a lack of simulations comprehensively addressing and comparing the bioaccumulation of PFAS across all three major exposure routes (oral, inhalation, and dermal), especially for dermal uptake. In this study, we proposed a physiologically based kinetic (PBK) model for PFAS, aiming to predict bioaccumulation factors (BAF) in fish by considering these diverse exposure routes. 15 PFAS were used for model validation, and 11 PFAS from Taihu Lake were used for exposure contribution modeling. Approximately 64% of estimations fell within 10-fold model bias from measurements in Taihu Lake, underscoring the potential efficacy of the developed PBK model in predicting BAFs for fish. The dermal route emerges as a contributor to short-chain PFAS exposure. For example, it ranged widely from 46% to 75% (mean) for all modeling short-chain PFAS (C6-C7) in Taihu Lake. It indicated the criticality of considering dermal exposure for PFAS in fish, highlighting a gap in field studies to unravel cutaneous intake mechanisms and contributions. For longer carbon chains of PFAS (C8-C12), dermal exposure accounted for 2%-27% for all species of aquatic organisms. The fish's lipid fraction and water content played a significant role in the contribution of PFAS intake through cutaneous exposure and inhalation. K ow had a significant positive correlation with skin intake rate (p < 0.05) and gill intake rate (p < 0.001), while having a significant negative correlation with skin intake (p < 0.05) and skin intake contribution (p < 0.001). Based on the proposed modeling approach, we have introduced a simulation spreadsheet for projecting PFAS BAFs in fish tissues, hopefully broadening the predictive operational tool for a variety of chemical species., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Per- and polyfluoroalkyl substances (PFAS) are a large class of stable toxic chemicals which have ended up in the environment and in organisms in significant concentrations. Toxicokinetic models are needed to facilitate extrapolation of bioaccumulation data across PFAS congeners and species. For the present study, we carried out an inventory of accumulation processes specific for PFAS, deviating from traditional Persistent Organic Pollutants (POPs). In addition, we reviewed toxicokinetic models on PFAS reported in literature, classifying them according to the number of compartments distinguished as a one-compartment model (1-CM), two-compartment model (2- CM) or a multi-compartment model, (multi-CM) as well as the accumulation processes included and the parameters used. As the inventory showed that simple 1-CMs were lacking, we developed a generic 1-CM of ourselves to include PFAS specific processes and validated the model for legacy perfluoroalkyl acids. Predicted summed elimination constants were accurate for long carbon chains (>C6), indicating that the model properly represented toxicokinetic processes for most congeners. Results for urinary elimination rate constants were mixed, which might be caused by the exclusion of reabsorption processes (renal reabsorption, enterohepatic circulation). The 1-CM needs to be improved further in order to better predict individual elimination pathways. Besides that, more data on PFAS-transporter specific processes are needed to extrapolate across PFAS congeners and species., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Globally, perfluoroalkyl acids (PFAA) are ubiquitous due to their almost unlimited applications in industry and households and are detected in a wide variety of matrices.Aquatic ecosystems are of particular importance due to the spread of PFAA via water fluxes. The majority of published studies describe PFAA concentrations in fish or aquatic mammals, but not the dependence of PFAA concentrations in tissues and organs in fish of different ages. Since this is very important for understanding the accumulation behavior of these substances our study systematically investigates the influence of age on the PFAA concentration in the tissues of 74 perches (Perca fluviatilis), a very popular edible fish. Fish are particularly suitable as indicators of PFAA contamination of water because of their uptake via water (gills and skin) and food (predominantly piscivorous diet). The mean total PFAA concentrations (as the sum of the individual concentrations of 11 compounds) were: 114 μg/kg (kidney), 112 μg/kg (heart), 79.9 μg/kg (liver), 78.4 μg/kg (spleen), 64.6 μg/kg (gills) and 21.7 μg/kg (muscle), with longer-chain compounds accounting for 90% of the substances. Perfluorooctanesulfoic acid (PFOS) accounted for the largest percentage of the total PFAA concentration in all tissues at 43-63%. With the exception of the heart and spleen, a significant increase in total concentrations was observed with increasing age of the perch. The strongest correlation was observed for the kidney, followed by the liver and gills. With regard to their consumption as human nutrition the tolerable weekly PFAA intake of 4.4 ng/kg bodyweight and week for the sum of the 4 EFSA PFAA in adults and children was exceeded many times over (860% and 1600% respectively) with an average fish consumption per week. The maximum PFAA levels set in the E.U. since January 2023 were exceeded five times., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Human hair is increasingly employed as a non-invasive biomonitoring matrix for exposure to organic contaminants (OCs). Decontamination procedures are generally needed to remove external contamination from hair prior to analysis of OCs. Despite various existing decontamination protocols, their impacts on internally incorporated (endogenous) OCs in hair remain poorly understood. This study aims to quantitatively assess the impact of decontamination procedures on endogenous OCs in hair, and investigate optimal decontamination processes and factors influencing the removal of endogenous OCs. In this study, guinea pig was exposed to 6 OCs (triphenyl phosphate (TPHP), tris(1,3-dichloro-2-propyl) phosphate (TDCPP), and tri-n-butyl phosphate (TNBP), bisphenol A (BPA), perfluorooctanoic acid (PFOA), and phenanthrene (PHE)), and 6 decontamination procedures with different solvents (methanol, n-hexane, acetone, ultrapure water, Triton X-100, and sodium dodecyl sulfate) were used to rinse exposed guinea pig hair. All OCs and three metabolites (diphenyl phosphate (DPHP), dibutyl phosphate (DBP), and bis(1,3-dichloro-2-propyl) phosphate (BDCPP)) were detected in the majority of washing solutions. The decontamination procedures apparently resulted in the release of endogenous OCs from hair. The percentages of residual OCs in hair exhibited a linear or exponential decrease with more washing cycles. Furthermore, the residuals of OCs in hair washed with organic and aqueous solvents showed negative correlations with molecular weight, polarizability, and their initial concentrations. Although these findings need to be validated with a broader range of OCs, the results obtained in this study provide compelling evidence that current hair decontamination procedures have significant impacts on the analysis of endogenous OCs in hair. Therefore, it is important to interpret quantitative data on hair OC concentrations with caution and to thoroughly consider each decontamination procedure during analysis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Perfluorooctanoic acid (PFOA) as emerging pollutants was largely produced and stable in nature environment. Its fate and effect to the wasted sludge digestion process and corresponding microbial mechanism was rarely reported. This study investigated the different dose of PFOA to the wasted sludge digestion process, where the methane yield and microbial mechanism was illustrated. The PFOA added before digestion were 0-10000 μg/L, no significant variation in daily and accumulated methane production between each group. The 9th day methane yield was significantly higher than other days (p < 0.05). The soluble protein was significantly decreased after 76 days digestion (p < 0.001). The total PFOA in sludge (R 2  = 0.8817) and liquid (R 2  = 0.9083) phase after digestion was exponentially correlated with PFOA dosed. The PFOA in liquid phase was occupied 54.10 ± 18.38% of the total PFOA in all reactors. The dewatering rate was keep decreasing with the increase of PFOA added (R 2  = 0.7748, p < 0.001). The mcrA abundance was significantly correlated with the pH value and organic matter concentration in the reactors. Chloroflexi was the predominant phyla, Aminicenantales, Bellilinea and Candidatus&#95;Cloacimonas were predominant genera in all reactors. Candidatus&#95;Methanofastidiosum and Methanolinea were predominant archaea in all reactors. The function prediction by FAPROTAX and Tax4fun implied that various PFOA dosage resulted in significant function variation. The fermentation and anaerobic chemoheterotrophy function were improved with the PFOA dose. Co-occurrence network implied the potent cooperation among the organic matter degradation and methanogenic microbe in the digestion system. PFOA has little impact to the methane generation while affect the microbe function significantly, its remaining in the digested sludge should be concerned to reduce its potential environmental risks., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The efficacy of RemBind® 300 to immobilize per- and polyfluoroalkyl substances (PFAS) in aqueous film forming foam (AFFF)-impacted soil (∑ 28 PFAS 1280-8130 ng g -1 ; n = 8) was assessed using leachability (ASLP) and bioaccumulation (Eisenia fetida) endpoints as the measure of efficacy. In unamended soil, ∑ 28 PFAS leachability ranged from 26.0 to 235 μg l -1 , however, following the addition of 5% w/w RemBind® 300, ∑ 28 PFAS leachability was reduced by > 99%. Following exposure of E. fetida to unamended soil, ∑ 28 PFAS bioaccumulation ranged from 18,660-241,910 ng g -1 DW with PFOS accumulating to the greatest extent (15,150-212,120 ng g -1 DW). Biota soil accumulation factors (BSAF) were significantly (p < 0.05) higher for perfluoroalkyl sulfonic acids (PFSA; 13.2-50.9) compared to perfluoroalkyl carboxylic acids (PFCA; 1.2-12.7) while for individual PFSA, mean BSAF increased for C 4 to C 6 compounds (PFBS: 42.6; PFPeS: 52.7; PFHxS: 62.4). In contrast, when E. fetida were exposed to soil amended with 5% w/w RemBind® 300, significantly lower PFAS bioaccumulation occurred (∑ 28 PFAS: 339-3397 ng g -1 DW) with PFOS accumulation 23-246 fold lower compared to unamended soil. These results highlight the potential of soil amendments for reducing PFAS mobility and bioavailability, offering an immobilization-based risk management approach for AFFF-impacted soil., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Perfluoroalkyl substances (PFASs) are emerging contaminants of increasing concern due to their presence in the environment, with potential impacts on ecosystems and human health. These substances are considered "forever chemicals" due to their recalcitrance to degradation, and their accumulation in living organisms can lead to varying levels of toxicity based on the compound and species analysed. Furthermore, concerns have been raised about the possible transfer of PFASs to humans through the consumption of edible parts of food plants. In this regard, to evaluate the potential toxic effects and the accumulation of perfluorooctanoic acid (PFOA) in edible plants, a pot experiment in greenhouse using three-week-old basil (Ocimum basilicum L.) plants was performed adding PFOA to growth substrate to reach 0.1, 1, and 10 mg Kg - 1 dw., Results: After three weeks of cultivation, plants grown in PFOA-added substrate accumulated PFOA at different levels, but did not display significant differences from the control group in terms of biomass production, lipid peroxidation levels (TBARS), content of α-tocopherol and activity of ascorbate peroxidase (APX), catalase (CAT) and guaiacol peroxidase (POX) in the leaves. A reduction of total phenolic content (TPC) was instead observed in relation to the increase of PFOA content in the substrate. Furthermore, chlorophyll content and photochemical reflectance index (PRI) did not change in plants exposed to PFAS in comparison to control ones. Chlorophyll fluorescence analysis revealed an initial, rapid photoprotective mechanism triggered by PFOA exposure, with no impact on other parameters (F v /F m , ΦPSII and qP). Higher activity of glutathione S-transferase (GST) in plants treated with 1 and 10 mg Kg - 1 PFOA dw (30 and 50% to control, respectively) paralleled the accumulation of PFOA in the leaves of plants exposed to different PFOA concentration in the substrate (51.8 and 413.9 ng g - 1 dw, respectively)., Conclusion: Despite of the absorption and accumulation of discrete amount of PFOA in the basil plants, the analysed parameters at biometric, physiological and biochemical level in the leaves did not reveal any damage effect, possibly due to the activation of a detoxification pathway likely involving GST., (© 2024. The Author(s).)

Perfluoroalkyl substances (PFAS) have been identified in various products that come in contact with human skin, ranging from school uniforms to personal care products. Despite this, knowledge on human dermal uptake of PFAS is lacking. Thus, the human dermal absorption of 17 PFAS was assessed, for the first time, using in vitro 3D-human skin equivalent models exposed to 500 ng/cm 2 PFAS dissolved in methanol over 24-36 h. The distribution of target PFAS is presented, based on three fractions: absorbed, un-absorbed, and retained within skin tissue (absorbable dose). Perfluoropentanoic acid (PFPeA) and perfluorobutane sulfonate (PFBS) had the highest absorbed fraction, 58.9 % and 48.7 % respectively, with the absorbed fraction decreasing with increasing carbon chain length of the studied perfluorocarboxylic acids (PFCAs) (r = 0.97, p = 0.001) and perfluorosulfonic acids (PFSAs) (r = 0.97, p = 0.004). Interestingly, while longer chain PFAS (C n  ≥ 9) were not directly absorbed, a large fraction of the exposure dose was detected within the skin tissue at the end of the exposure. This was most apparent for perfluoroundecanoic acid (PFUnDA) and perfluorononane sulfonate (PFNS) for which 66.5 % and 68.3 % of the exposure dose was found within the skin tissue, while neither compound was detected in the absorbed fraction. For compounds with a carbon chain length > 11, the fraction found within the skin tissue, decreases with increasing chain length. Physicochemical properties played a role in dermal permeation of PFAS, with a clear inverse correlation between logK OW and absorbed fraction for both PFCAs (r = -0.97; p ≤ 0.001) and PFSAs (r = -0.99; p ≤ 0.001). Steady-state flux (J SS ) and permeation coefficients (P app ) were determined for target compounds with significant permeation after 36 h exposure (C 5 -C 8 PFCAs and C 4 -C 7 PFSAs). In general, both the flux and permeation coefficient decreased with increasing chain length., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Perfluorooctane sulfonate (PFOS) is a prominent perfluorinated compound commonly found in the environment, known to pose various risks to human health. However, the removal of PFOS presents significant challenges, primarily due to the limited discovery of bacteria capable of effectively degrading PFOS. Moreover, single degradation bacteria often encounter obstacles in individual cultivation and the breakdown of complex pollutants. In contrast, microbial consortia have shown promise in pollutant degradation. This study employed a continuous enrichment method, combined with multiple co-metabolic substrates, to investigate a microbial consortium with the potential for PFOS degradation. By employing this methodology, we effectively identified a microbial consortium that demonstrated the capacity to reduce PFOS when exposed to an optimal concentration of methanol. The consortium predominantly comprised of Hyphomicrobium species (46.7%) along with unclassified microorganisms (53.0%). Over a duration of 20 days, the PFOS concentration exhibited a notable decrease of 56.7% in comparison to the initial level, while considering the exclusion of adsorption effects. Furthermore, by comparing the predicted metabolic pathways of the microbial consortium with the genome of a known chloromethane-degrading bacterium, Hyphomicrobium sp. MC1, using the KEGG database, we observed distinct variations in the metabolic pathways, suggesting the potential role of the unclassified microorganisms. These findings underscore the potential effectiveness of a "top-down" functional microbial screening approach in the degradation of stubborn pollutants., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Liang, Ma. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Legacy and emerging per- and polyfluoroalkyl substances (PFASs) were measured in livers of finless porpoises (Neophocaena asiaeorientalis; n = 167) collected in Korean waters from 2002 to 2015 to investigate their occurrence, bioaccumulation feature, temporal trends, and ecotoxicological implications. Perfulorooctane sulfonate (PFOS), perfluoroundecanoate (PFUnDA), and perfluorotridecanoate (PFTrDA) were the predominant PFASs found in the porpoises. The concentration of 6:2 chlorinated polyfluoroalkyl ether sulfonate (F-53B), an alternative to PFOS, was comparable to that of PFTrDA. Perfluorooctane sulfonamide (FOSA), a precursor of PFOS, was also detected in all the porpoises examined. All PFASs, including F-53B, accumulated to higher concentrations in immature porpoises compared with mature specimens, implying substantial maternal transfer and limited metabolizing capacity for PFASs. A significant correlation was observed between PFOS and F-53B concentrations, indicating similar bioaccumulation processes. Based on prenatal exposure and toxicity, F-53B is an emerging contaminant in marine ecosystems. Significantly increasing trends were observed in the concentrations of sulfonates, carboxylates, and F-53B between 2002/2003 and 2010, whereas the FOSA concentration significantly decreased. During 2010-2015, decreasing trends were observed in the concentrations of FOSA and sulfonates, whereas concentrations of carboxylate and F-53B increased without statistical significance, likely due to a gap for the implementation of regulatory actions between sulfonates and carboxylates. Although PFOS and PFOA were found to pose little health risk to porpoises, the combined toxicological effects of other contaminants should be considered to protect populations and to mitigate PFAS contamination in marine ecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Per- and polyfluoroalkyl substances (PFAS) are widely used synthetic chemicals that persist in the environment and bioaccumulate in animals and humans. There is growing evidence that PFAS exposure adversely impacts neurodevelopment and neurological health. Steroid 5α-reductase 1 (SRD5A1) plays a key role in neurosteroidogenesis by catalyzing the conversion of testosterone or pregnenolone to neuroactive steroids, which influence neural development, cognition, mood, and behavior. This study investigated the inhibitory strength and binding interactions of 18 PFAS on human and rat SRD5A1 activity using enzyme assays, molecular docking, and structure-activity relationship analysis. Results revealed that C9-C14 PFAS carboxylic acid at 100 μM significantly inhibited human SRD5A1, with IC 50 values ranged from 10.99 μM (C11) to 105.01 μM (C14), and only one PFAS sulfonic acid (C8S) significantly inhibited human SRD5A1 activity, with IC 50 value of 8.15 μM. For rat SRD5A1, C9-C14 PFAS inhibited rat SRD5A1, showing the similar trend, depending on carbon number of the carbon chain. PFAS inhibit human and rat SRD5A1 in a carbon chain length-dependent manner, with optimal inhibition around C11. Kinetic studies indicated PFAS acted through mixed inhibition. Molecular docking revealed PFAS bind to the domain between NADPH and testosterone binding site of both SRD5A1 enzymes. Inhibitory potency correlated with physicochemical properties like carbon number of the carbon chain. These findings suggest PFAS may disrupt neurosteroid synthesis and provide insight into structure-based inhibition of SRD5A1., Competing Interests: Declaration of competing interest The authors have no conflict of interest to be disclosed., (Copyright © 2024. Published by Elsevier B.V.)

Compost is widely used in agriculture as fertilizer while providing a practical option for solid municipal waste disposal. However, compost may also contain per- and polyfluoroalkyl substances (PFAS), potentially impacting soils and leading to PFAS entry into food chains and ultimately human exposure risks via dietary intake. This study examined how compost affects the bioavailability and uptake of eight PFAS (two ethers, three fluorotelomer sulfonates, and three perfluorosulfonates) by lettuce (Lactuca sativa) grown in commercial organic compost-amended, PFAS spiked soils. After 50 days of greenhouse experiment, PFAS uptake by lettuce decreased (by up to 90.5 %) with the increasing compost amendment ratios (0-20 %, w/w), consistent with their decreased porewater concentrations (by 30.7-86.3 %) in compost-amended soils. Decreased bioavailability of PFAS was evidenced by the increased in-situ soil-porewater distribution coefficients (K d ) (by factors of 1.5-7.0) with increasing compost additions. Significant negative (or positive) correlations (R 2  ≥ 0.55) were observed between plant bioaccumulation (or K d ) and soil organic carbon content, suggesting that compost amendment inhibited plant uptake of PFAS mainly by increasing soil organic carbon and enhancing PFAS sorption. However, short-chain PFAS alternatives (e.g., perfluoro-2-methoxyacetic acid (PFMOAA)) were effectively translocated to shoots with translocation factors > 2.9, increasing their risks of contamination in leafy vegetables. Our findings underscore the necessity for comprehensive risk assessment of compost-borne PFAS when using commercial compost products in agricultural lands., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

A plethora of studies have shown the prominent hepatotoxicity caused by perfluorooctane sulfonate (PFOS), yet the research on the causality of F-53 B (an alternative for PFOS) exposure and liver toxicity, especially in mammals, is largely limited. To investigate the effects that chronic exposure to F-53 B exert on livers, in the present study, male SD rats were administrated with F-53 B in a certain dose range (0, 1, 10, 100, 1000 μg/L, eight rats per group) for 6 months via drinking water and the hepatotoxicity resulted in was explored. We reported that chronic exposure to 100 and 1000 μg/L F-53 B induced remarkable histopathological changes in liver tissues such as distinct swollen cells and portal vein congestion. In addition, the increase of cytokines IL-6, IL-2, and IL-8 upon long-term administration of F-53 B demonstrated the high level of inflammation. Moreover, F-53 B exposure was revealed to disrupt the lipid metabolism in the rat livers, mainly manifesting as the upregulation of some proteins involved in lipid synthesis and degradation, including ACC, FASN, SREBP-1c as well as ACOX1. These findings provided new evidence for the adverse effects caused by chronic exposure to F-53 B in rodents. It is crucial for industries, regulatory agencies as well as the public to remain vigilant about the adverse health effects associated with the emerging PFOS substitutes such as F-53 B. Implementation of regular monitoring and risk assessments is of great importance to alleviate environmental concerns towards PFOS alternatives exposure, and furthermore, to minimize the latent health risks to the public health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Per- and polyfluoroalkyl substances (PFAS), ubiquitous environmental contaminants, pose significant challenges to ecosystems and human health. While cell cultures have emerged as new approach methodologies (NAMs) in ecotoxicity research, metabolomics is an emerging technique used to characterize the small-molecule metabolites present in cells and to understand their role in various biological processes. Integration of metabolomics with cell cultures, known as cell culture metabolomics, provides a novel and robust tool to unravel the complex molecular responses induced by PFAS exposure. In vitro testing also reduces reliance on animal testing, aligning with ethical and regulatory imperatives. The current review summarizes key findings from recent studies utilizing cell culture metabolomics to investigate PFAS toxicity, highlighting alterations in metabolic pathways, biomarker identification, and the potential linkages between metabolic perturbations. Additionally, the paper discusses different types of cell cultures and metabolomics methods used for studies of environmental contaminants and particularly PFAS. Future perspectives on the combination of metabolomics with other advanced technologies, such as single-cell metabolomics (SCM), imaging mass spectrometry (IMS), extracellular flux analysis (EFA), and multi-omics are also explored, which offers a holistic understanding of environmental contaminants. The synthesis of current knowledge and identification of research gaps provide a foundation for future investigations that aim to elucidate the complexities of PFAS-induced cellular responses and contribute to the development of effective strategies for mitigating their adverse effects on human health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Exposure to poly- and perfluoroalkyl substances (PFASs) can result in bioaccumulation. Initial findings suggested that PFASs could accumulate in tissues rich in both phospholipids and proteins. However, our current understanding is limited to the average concentration of PFASs or phospholipid content across entire tissue matrices, leaving unresolved the spatial variations of lipid metabolism associated with PFOA in zebrafish tissue. To address gap, we developed a novel methodology for concurrent spatial profiling of perfluorooctanoic acid (PFOA) and individual phospholipids within zebrafish hepatic tissue sections, utilizing matrix-assisted laser desorption/ionization time of flight imaging mass spectrometry (MALDI-TOF-MSI). 5-diaminonapthalene (DAN) matrix and laser sensitivity of 50.0 were optimized for PFOA detection in MALDI-TOF-MSI analysis with high spatial resolution (25 μm). PFOA was observed to accumulate within zebrafish liver tissue. H&E staining results corroborating the damage inflicted by PFOA accumulation, consistent with MALDI MSI results. Significant up-regulation of 15 phospholipid species was observed in zebrafish groups exposed to PFOA, with these phospholipid demonstrating varied spatial distribution within the same tissue. Furthermore, co-localized imaging of distinct phospholipids and PFOA within identical tissue sections suggested there could be two distinct potential interactions between PFOA and phospholipids, which required further investigation. The MALDI-TOF-IMS provides a new tool to explore in situ spatial distributions and variations of the endogenous metabolites for the health risk assessment and ecotoxicology of emerging environmental pollutants., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

The perfluoalkyl substance (PFASs) perfluorooctane sulfonate (PFOS) has been widely used in industry. However, PFOS is a persistent organic pollutant and has been gradually replaced by its short-chain analogs, perfluorohexane sulfonate (PFHxS) and perfluorobutane sulfonate (PFBS). PFASs are extremely persistent and are very frequently detected among the general population. The aim of the study was to determine the effect of selected PFASs on peripheral blood mononuclear cells (PBMCs) and the mechanisms of their action. PBMCs were exposed to PFOS, PFBS and PFHxS at concentrations ranging from 0.02 to 400 μM for 24 h, they were then tested for viability, apoptosis (changes in cytosolic calcium ions level and caspase-3, -8 and -9 activation), ferroptosis (changes in chelatable iron ions level and lipid peroxidation), and autophagy (LC3-II and Raptor level assay). PFOS exposure decreased cell viability, increased calcium ion level and caspase-8 activation; it also enhanced lipid peroxidation and increased the intracellular pool of chelatable iron ions as well as LC3-II protein content. In contrast, short-chain PFBS and PFHxS induced significant changes in the markers of apoptosis but had no substantial impact on ferroptosis or autophagy markers over a wide range of concentrations. Our results indicate that only PFOS demonstrated pro-ferroptotic and pro-autophagic potential but observed changes occurred at relatively high exposure. A short-chain substitute (PFBS) exhibited strong pro-apoptotic potential at concentrations related to occupational exposure. While the short-chain PFASs strongly affected the mitochondrial pathway of apoptosis, apoptosis itself was only induced by PFBS via the intrinsic and extrinsic pathways. It seems that the length of the carbon chain in PFASs appears to determine the cell death mechanisms activated in human PBMCs following exposure. Our findings provide a new insight into the immune toxicity mechanism induced by these compounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

As a result of proposed global restrictions and regulations on current-use per-and polyfluoroalkyl substances (PFAS), research on possible alternatives is highly required. In this study, phase I in vitro metabolism of two novel prototype PFAS in human and rat was investigated. These prototype chemicals are intended to be safer-by-design and expected to mineralize completely, and thus be less persistent in the environment compared to the PFAS available on the market. Following incubation with rat liver S9 (RL-S9) fractions, two main metabolites per initial substance were produced, namely an alcohol and a short-chain carboxylic acid. While with human liver S9 (HL-S9) fractions, only the short-chain carboxylic acid was detected. Beyond these major metabolites, two and five additional metabolites were identified at very low levels by non-targeted screening for the ether- and thioether-linked prototype chemicals, respectively. Overall, complete mineralization during the in vitro hepatic metabolism of these novel PFAS by HL-S9 and RL-S9 fractions was not observed. The reaction kinetics of the surfactants was determined by using the metabolite formation, rather than the substrate depletion approach. With rat liver enzymes, the formation rates of primary metabolite alcohols were at least two orders of magnitude higher than those of secondary metabolite carboxylic acids. When incubating with human liver enzymes, the formation rates of single metabolite carboxylic acids, were similar or smaller than those experienced in rat. It also indicates that the overall metabolic rate and clearance of surfactants are significantly higher in rat liver than in human liver. The maximum formation rate of the thioether congener exceeded 10-fold that of the ether in humans but were similar in rats. Overall, the results suggest that metabolism of the prototype chemicals followed a similar trend to those reported in studies of fluorotelomer alcohols., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Anthropogenic pollution is identified as an important threat to bird and other wildlife populations. Many metals and toxic elements, along with poly- and perfluoroalkyl substances (PFASs) are known to induce immunomodulation and have previously been linked to increased pathogen prevalence and infectious disease severity. In this study, the house sparrow (Passer domesticus) was investigated at the coast of Helgeland in northern Norway. This population is commonly infected with the parasitic nematode "gapeworm" (Syngamus trachea), with a prevalence of 40-60 % during summer months. Gapeworm induces severe respiratory disease in birds and has been previously demonstrated to decrease survival and reproductive success in wild house sparrows. The aim of this study was to investigate whether a higher exposure to pollution with PFASs, metals and other elements influences gapeworm infection in wild house sparrows. We conducted PFASs and elemental analysis on whole blood from 52 house sparrows from Helgeland, including analyses of highly toxic metals such as lead (Pb), mercury (Hg) and arsenic (As). In addition, we studied gapeworm infection load by counting the parasite eggs in faeces from each individual. We also studied the expression of microRNA 155 (miR155) as a key regulator in the immune system. Elevated blood concentrations of Pb were found to be associated with an increased prevalence of gapeworm infection in the house sparrow. The expression of miR155 in the plasma of the house sparrow was only weakly associated with Pb. In contrast, we found relatively low PFASs concentrations in the house sparrow blood (∑ PFASs 0.00048-354 μg/L) and PFASs were not associated to miR155 nor infection rate. The current study highlights the potential threat posed by Pb as an immunotoxic pollutant in small songbirds., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Essa Ahsan Khan reports financial support was provided by Norwegian University of Science and Technology. Henrik Jensen and Veerle L.B. Jaspers reports financial support was provided by Research Council of Norway. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Despite their use as substitutes for perfluorooctanoic acid, the potential toxicities of hexafluoropropylene oxide dimer acid (HFPO-DA, commercial name: GenX) and its analogs (PFDMOHxA, PFDMO2HpA, and PFDMO2OA) remain poorly understood. To assess the hepatotoxicity of these chemicals on females, each chemical was orally administered to female C57BL/6 mice at the dosage of 0.5 mg/kg/d for 28 d. The contribution of peroxisome proliferator-activated receptors (PPARα and γ) and other nuclear receptors involving in these toxic effects of GenX and its analogs were identified by employing two PPAR knockout mice (PPARα -/- and PPARγ ΔHep ) in this study. Results showed that the hepatotoxicity of these chemicals increased in the order of GenX < PFDMOHxA < PFDMO2HpA < PFDMO2OA. The increases of relative liver weight and liver injury markers were significantly much lower in PPARα -/- mice than in PPARα +/+ mice after GenX analog exposure, while no significant differences were observed between PPARγ ΔHep and its corresponding wildtype groups (PPARγ F/F mice), indicating that GenX analog induce hepatotoxicity mainly via PPARα instead of PPARγ. The PPARα-dependent complement pathways were inhibited in PFDMO2HpA and PFDMO2OA exposed PPARα +/+ mice, which might be responsible for the observed liver inflammation. In PPARα -/- mice, hepatomegaly and increased liver lipid content were observed in PFDMO2HpA and PFDMO2OA treated groups. The activated pregnane X receptor (PXR) and constitutive activated receptor (CAR) pathways in the liver of PPARα -/- mice, which were highlighted by bioinformatics analysis, provided a reasonable explanation for hepatomegaly in the absence of PPARα. Our results indicate that GenX analogs could induce more serious hepatotoxicity than GenX whether there is a PPARα receptor or not. These chemicals, especially PFDMO2HpA and PFDMO2OA, may not be appropriate PFOA alternatives., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nan Sheng reports financial support was provided by National Natural Science Foundation of China. Jiayin Dai reports financial support was provided by National Natural Science Foundation of China., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Per- and poly-fluoroalkyl substances (PFAS), such as GenX, are a class of highly stable synthetic compounds that have recently become the focus of environmental remediation endeavors due to their toxicity. While considerable strides have been made in PFAS remediation, the diversity of these compounds, and the costs associated with approaches such as ion exchange resins and advanced oxidation technologies, remain challenging for widespread application. In addition, little is known about the potential binding and impacts of GenX on human proteins. To address these issues, we applied phage display and screened short peptides that bind specifically to GenX, with the ultimate goal of identifying human proteins that bind with GenX. In this study we identified the amino acids that contribute to the binding and measured the binding affinities of the two discovered peptides with NMR. A human protein, ankyrin-repeat-domain-containing protein 36B, with matching sequences of one of the peptides, was identified, and the binding positions were predicted by docking and molecular dynamics simulation. This study created a platform to screen peptides that bind with toxic chemical compounds, which ultimately helped us identify biologically relevant molecules that could be inhibited by the GenX, and also provided information that will contribute to future bioengineered GenX-binding device design.

Background: Per- and polyfluoroalkyl substances (PFAS) constitute a heterogeneous group of synthetic compounds widely used in industrial applications. The estimation of PFAS half-life (t 1/2 ) is essential to quantify their persistence, their toxicity and mechanism of action in humans., Objectives: The purpose of this review is to summarize the evidence on PFAS half-lives in humans from the available literature, and to investigate the limitations and uncertainties characterizing half-life estimation., Methods: The search was conducted on PubMed, Scopus, and Embase databases up to July 03, 2023 and was aimed at identifying all papers that estimated PFAS half-life in human populations. We excluded studies on temporal trends or providing estimates of half-life based solely on renal clearance. As persistent and ongoing exposures can influence half-life estimation, we decided to include only studies that were conducted after the main source of exposure to PFAS had ceased. A random-effects meta-analysis was conducted on studies that reported perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS) or perfluorohexanesulfonic acid (PFHxS) half-life estimation. Risk of bias was evaluated using the OHAT tool., Results: A total of 13 articles were included in the review, with 5 studies conducted in exposed general populations and 8 studies conducted in exposed workers; the estimated mean half-life ranged from 1.48 to 5.1 years for PFOA, from 3.4 to 5.7 years for total PFOS, and from 2.84 to 8.5 years for PFHxS. High heterogeneity among studies was observed; potential reasons include the variability among the investigated populations, discrepancies in considering ongoing exposures, variability in PFAS isomeric compositions, accounting for background exposure, time since exposure stopped and methods used for half-life estimation., Discussion: Despite the efforts made to better understand PFAS toxicokinetics, further studies are needed to identify important characteristics of these persistent chemicals. Biomonitoring studies should focus on persistent and unaccounted sources of exposure to PFAS and on individual characteristics potentially determining half-life, to ensure accurate estimates., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Perfluorooctane sulfonate (PFOS), an endocrine-disrupting chemical pollutant, affects embryonic heart development; however, the mechanisms underlying its toxicity have not been fully elucidated. Here, Single-cell RNA sequencing (scRNA-seq) was used to investigate the overall effects of PFOS on myocardial differentiation from human embryonic stem cells (hESCs). Additionally, apoptosis, mitochondrial membrane potential, and ATP assays were performed. Downregulated cardiogenesis-related genes and inhibited cardiac differentiation were observed after PFOS exposure in vitro. The percentages of cardiomyocyte and cardiac progenitor cell clusters decreased significantly following exposure to PFOS, while the proportion of primitive endoderm cell was increased in PFOS group. Moreover, PFOS inhibited myocardial differentiation and blocked cellular development at the early- and middle-stage. A Gene Ontology analysis and pseudo-time trajectory illustrated that PFOS disturbed multiple processes related to cardiogenesis and oxidative phosphorylation in the mitochondria. Furthermore, PFOS decreased mitochondrial membrane potential and induced apoptosis. These results offer meaningful insights into the cardiogenic toxicity of PFOS exposure during heart formation as well as the adverse effects of PFOS on mitochondria., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Perfluorooctanoic acid (PFOA) is one of the major per- and polyfluoroalkyl substances. The role of ATP-binding cassette (ABC) transporters in PFOA toxicokinetics is unknown., Methods: In this study, two ABC transporters, ABCB1 and ABCB4, were examined in mice with single intravenous PFOA administration (3.13 µmol/kg). To identify candidate renal PFOA transporters, we used a microarray approach to evaluate changes in gene expression of various kidney transporters in Abcb4 null mice., Results: Biliary PFOA concentrations were lower in Abcb4 null mice (mean ± standard deviation: 0.25 ± 0.12 µg/mL) than in wild-type mice (0.87 ± 0.02 µg/mL). Immunohistochemically, ABCB4 expression was confirmed at the apical region of hepatocytes. However, renal clearance of PFOA was higher in Abcb4 null mice than in wild-type mice. Among 642 solute carrier and ABC transporters, 5 transporters showed significant differences in expression between wild-type and Abcb4 null mice. These candidates included two major xenobiotic transporters, multidrug resistance 1 (Abcb1) and organic anion transporter 3 (Slc22a8). Abcb1 mRNA levels were higher in Abcb4 null mice than in wild-type mice in kidney. In Abcb4 null mice, Abcb1b expression was enhanced in proximal tubules immunohistochemically, while that of Slc22a8 was not. Finally, in Abcb1a/b null mice, there was a significant decrease in the renal clearance of PFOA (0.69 ± 0.21 vs 1.1 mL ± 0.37/72 h in wild-type mice). A homology search of ABCB1 showed that several amino acids are mutated in humans compared with those in rodents and monkeys., Conclusions: These findings suggest that, in the mouse, Abcb4 and Abcb1 are excretory transporters of PFOA into bile and urine, respectively.

Perfluorooctanoic acid (PFOA) is becoming a concern due to its persistence, bioaccumulation, and potential harmful effects on humans and the environment. In this study, the fungus Phanerochaete chrysosporium (P. chrysosporium) was used to remove the PFOA in liquid culture system. The results showed that the average activities of laccase (Lac), lignin peroxidase (LiP), and manganese peroxidase (MnP) enzymes secreted by P. chrysosporium were 0.0003 U/mL, 0.013 U/mL, and 0.0059 U/mL, respectively, during the incubation times of 0-75 days. The pH of 3 and incubation time of 45-55 days were the optimum parameters for the three enzymes activities. The enzyme activities in P. chrysosporium incubation system were firstly inhibited by adding PFOA and then they were enhanced after 14 days. The maximum removal efficiency of PFOA (69.23%) was achieved after 35 days in P. chrysosporium incubation system with an initial PFOA concentration of 0.002 mM and no veratryl alcohol (VA). Adsorption was not a main pathway for PFOA removal and the PFOA adsorbed in fungi mycelial mat accounted for merely 1.91%. The possible products of PFOA contained partially fluorinated aldehyde, alcohol, and aromatic ring. These partially fluorinated compounds might result from PFOA degradation via a combination of cross-coupling and rearrangement of free radicals., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hui Mao reports financial support was provided by Shaanxi Province Natural Science Foundation., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Persistent organic pollutant perfluorooctane sulfonate (PFOS) is strongly associated with male reproductive disorders, but the related mechanisms are still not fully understood. In this study, we used in vivo and in vitro models to explore the role of organic anion transporting polypeptide 3a1 (Oatp3a1) on PFOS-induced male reproductive injury. Thirty male C57BL/6 (B6) mice were orally given PFOS (0-10 mg/kg/bw) for 28 days. Body weight, organ index, sperm count, histology, and blood-testis barrier (BTB) integrity were evaluated. Primary Sertoli cells were used to describe the related molecular mechanisms of male reproductive injury caused by PFOS. Our results showed that PFOS induced a decrease in sperm count, morphological damage to testicular Sertoli cells, and disruption of BTB. In the in vitro model, exposure to PFOS significantly increased Oatp3a1 mRNA and protein levels and decreased miR-23a-3p expression in Sertoli cells, accompanied by reduced trans-epithelial electrical resistance (TEER) value. By performing the 14 C-PFOS uptake experiment, we showed that 14 C-PFOS uptake in HEK293-Oatp3a1 cells was apparently higher than in HEK293-MOCK cells. Meanwhile, treating Sertoli cells with Oatp3a1 siRNA significantly decreased Oatp3a1 expression and rescued PFOS-induced decreases in TEER value. As such, the present study highlights that Oatp3a1 may play an important role in the toxic effect of PFOS on Sertoli cells, advancing our understanding of molecular mechanisms for PFOS-induced male reproductive disorders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Climate change and pollution are increasingly important stress factors for life on Earth. Dispersal of poly- and perfluoroalkyl substances (PFAS) are causing worldwide contamination of soils and water tables. PFAS are partially hydrophobic and can easily bioaccumulate in living organisms, causing metabolic alterations. Different plant species can uptake large amounts of PFAS, but little is known about its consequences for the plant water relation and other physiological processes, especially in woody plants. In this study, we investigated the fractionation of PFAS bioaccumulation from roots to leaves and its effects on the conductive elements of willow plants. Additionally, we focused on the stomal opening and the phytohormonal content. For this purpose, willow cuttings were exposed to a mixture of 11 PFAS compounds and the uptake was evaluated by LC-MS/MS. Stomatal conductance was measured and the xylem vulnerability to air embolism was tested and further, the abscisic acid and salicylic acid contents were quantified using LC-MS/MS. PFAS accumulated from roots to leaves based on their chemical structure. PFAS-exposed plants showed reduced stomatal conductance, while no differences were observed in abscisic acid and salicylic acid contents. Interestingly, PFAS exposure caused a higher vulnerability to drought-induced xylem embolism in treated plants. Our study provides novel information about the PFAS effects on the xylem hydraulics, suggesting that the plant water balance may be affected by PFAS exposure. In this perspective, drought events may be more stressful for PFAS-exposed plants, thus reducing their potential for phytoremediation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Perfluorohexane sulfonate (PFHxS) is a frequently detected per- and polyfluoroalkyl substance in most populations, including in individuals who are pregnant, a period critical for early life development. Despite epidemiological evidence of exposure, developmental toxicity, particularly at realistic human exposures, remains understudied., Objectives: We evaluated the effect of gestational exposure to human-relevant body burden of PFHxS on fetal and placental development and explored mechanisms of action combining alternative splicing (AS) and gene expression (GE) analyses., Methods: Pregnant ICR mice were exposed to 0, 0.03, and 0.3 μ g / kg / day  from gestational day 7 to day 17 via oral gavage. Upon euthanasia, PFHxS distribution was measured using liquid chromatography-tandem mass spectrometry. Maternal and fetal phenotypes were recorded, and histopathology was examined for placenta impairment. Multiomics was adopted by combining AS and GE analyses to unveil disruptions in mRNA quality and quantity. The key metabolite transporters were validated by quantitative real-time PCR (qRT-PCR) for quantification and three-dimensional (3D) structural simulation by AlphaFold2. Targeted metabolomics based on liquid chromatography-tandem mass spectrometry was used to detect amino acid and amides levels in the placenta., Results: Pups developmentally exposed to PFHxS exhibited signs of intrauterine growth restriction (IUGR), characterized by smaller fetal weight and body length ( p < 0.01 ) compared to control mice. PFHxS concentration in maternal plasma was 5.01 ± 0.54  ng / mL . PFHxS trans-placenta distribution suggested dose-dependent transfer through placental barrier. Histopathology of placenta of exposed dams showed placental dysplasia, manifested with an attenuated labyrinthine layer area and deescalated blood sinus counts and placental vascular development index marker CD34. Combined GE and AS analyses pinpointed differences in genes associated with key biological processes of placental development, proliferation, metabolism, and transport in placenta of exposed dams compared to that of control dams. Further detection of placental key transporter gene expression, protein structure simulation, and amino acid and amide metabolites levels suggested that PFHxS exposure during pregnancy led to impairment of placental amino acid transportation., Discussion: The findings from this study suggest that exposure to human-relevant very-low-dose PFHxS during pregnancy in mice caused IUGR, likely via downregulating of placental amino acid transporters, thereby impairing placental amino acid transportation, resulting in impairment of placental development. Our findings confirm epidemiological findings and call for future attention on the health risk of this persistent yet ubiquitous chemical in the early developmental stage and provide a new approach for understanding gene expression from both quantitative and qualitative omics approaches in toxicological studies. https://doi.org/10.1289/EHP13217.

Perfluorooctanoic acid (PFOA) is a type of toxic per- and poly-fluoroalkyl substance (PFAS) commonly found in groundwater due to its use in firefighting and industrial applications. The main purpose of this study was to investigate the influence of PFOA shock on the biological performance of a hydrogen-driven bioreactor for nitrate and arsenate removal. Four hydrogen-driven removal reactors (HdBRs) used for the simultaneous removal of nitrate and arsenal were operated with concentrations of either 0, 1, 5, and 10 mg/L of PFOA to induce shock on the systems and examine the corresponding bacterial response. Our results showed that PFOA shock inhibited and decreased the maximum hydrogen-driven arsenate removal rate. Principal Component Analysis (PCA) confirmed that this performance decrease occurred due to a bacterial strike triggered by PFOA shock. PFOA toxicity also led to protein secretion and sludge density decreases. Bacterial analyses showed shifts in the community population due to PFOA shock. The dominant bacteria phylum Proteobacteria became more abundant, from 41.24% originally to 48.29% after exposure to 10 mg/L of PFOA. Other phyla, such as Euryarchaeota and Bacteroidetes, were more tolerant to PFOA shock. Although some of the predominant species within the sludge of each HdBR exhibited a decline, other species with similar functions persisted and assumed the functional responsibilities previously held by the dominant species., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The present study investigates the impact of two endocrine disruptors, namely Bisphenols (BPs) and Perfluoroalkyls (PFs), on human stem cells. These chemicals leach from plastic, and when ingested through contaminated food and water, they interfere with endogenous hormone signaling, causing various diseases. While the ability of BPs and PFs to cross the placental barrier and accumulate in fetal serum has been documented, the exact consequences for human development require further elucidation. The present research work explored the effects of combined exposure to BPs (BPA or BPS) and PFs (PFOS and PFOA) on human placenta (fetal membrane mesenchymal stromal cells, hFM-MSCs) and amniotic fluid (hAFSCs)-derived stem cells. The effects of the xenobiotics were assessed by analyzing cell proliferation, mitochondrial functionality, and the expression of genes involved in pluripotency and epigenetic regulation, which are crucial for early human development. Our findings demonstrate that antenatal exposure to BPs and/or PFs may alter the biological characteristics of perinatal stem cells and fetal epigenome, with potential implications for health outcomes at birth and in adulthood. Further research is necessary to comprehend the full extent of these effects and their long-term consequences.

Perfluoroundecanoic acid (PFUnA) is an eleven carbon-chain compound that belongs to the perfluoroalkyl carboxylic acid family. It has been detected in the human blood, effluents, and surface/ground waters, but its toxic effects to the DNA and reproductive system remain unclear. This study was aimed at exploring the toxicity of PFUnA on the hepatic DNA, organ-system and reproductive system in orally treated male Swiss mice. In this present study, administration of PFUnA for 28 days with five doses (0.1, 0.3, 05, 0.7 and 1.0 mg kg-1 b.w./d) in male Swiss mice induced significant hepatic DNA damage which was observed using the alkaline comet assay and equally altered hematological and clinical biochemical parameters. In addition to testicular atrophy, sperm count and sperm motility significantly decreased while sperm abnormalities increased after 35 days exposure. Serum LH and FSH levels were remarkably increased while serum testosterone levels were strikingly reduced. Histopathology revealed the liver, kidney, and testis as potential targets of PFUnA toxicity. Increased activities of superoxide dismutase (SOD) and catalase (CAT), as well as levels of glutathione-s-transferase (GST) and reduced glutathione (GSH), with consistent reduction of glutathione peroxidase (GPx) and reduced glutathione (GSH) in the liver and testis induced oxidative stress. In conclusion, PFUnA exhibited both genotoxicity and reproductive toxicity via oxidative stress induction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

In the last decades, per- and poly-fluoroalkyl substances (PFAS), widely used industrial chemicals, have been in the center of attention because of their omnipotent presence in water and soils worldwide. Although efforts have been made to substitute long-chain PFAS towards safer alternatives, their persistence in humans still leads to exposure to these compounds. PFAS immunotoxicity is poorly understood as no comprehensive analyses on certain immune cell subtypes exist. Furthermore, mainly single entities and not PFAS mixtures have been assessed. In the present study we aimed to investigate the effect of PFAS (short-chain, long-chain and a mixture of both) on the in vitro activation of primary human immune cells. Our results show the ability of PFAS to reduce T cells activation. In particular, exposure to PFAS affected T helper cells, cytotoxic T cells, Natural Killer T cells, and Mucosal associated invariant T (MAIT) cells, as assessed by multi-parameter flow cytometry. Furthermore, the exposure to PFAS reduced the expression of several genes involved in MAIT cells activation, including chemokine receptors, and typical proteins of MAIT cells, such as GZMB, IFNG and TNFSF15 and transcription factors. These changes were mainly induced by the mixture of both short- and long-chain PFAS. In addition, PFAS were able to reduce basophil activation induced by anti-FcεR1α, as assessed by the decreased expression of CD63. Our data clearly show that the exposure of immune cells to a mixture of PFAS at concentrations mimicking real-life human exposure resulted in reduced cell activation and functional changes of primary innate and adaptive human immune cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

GenX, also known as hexafluoropropylene oxide dimer acid (HFPO-DA) was introduced as a safer alternative to perfluorooctanoic acid (PFOA) in 2009. After nearly two decades of applications there are increasing safety concerns about GenX due to its association with various organ damages. Few studies, however, have systematically assessed the molecular neurotoxicity of low-dose GenX exposure. Here, we evaluated the effects of pre-differentiation exposure of GenX on dopaminergic (DA) -like neurons using SH-SY5Y cell line; and assessed changes in epigenome, mitochondrion, and neuronal characteristics. Low dose GenX exposure at 0.4 and 4 μg/L prior to differentiation induced persistent changes in nuclear morphology and chromatin arrangements, manifested specifically in the facultative repressive marker H3K27me3. We also observed impaired neuronal network, increased calcium activity along with alterations in Tyrosine hydroxylase (TH) and α-Synuclein (αSyn) after prior exposure to GenX. Collectively, our results identified neurotoxicity of low-dose GenX exposure in human DA-like neurons following a developmental exposure scheme. The observed changes in neuronal characteristics suggest GenX as a potential neurotoxin and risk factor for Parkinson's disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) have raised concerns regarding sex hormones homeostasis disruption in critical windows including childhood and adolescence, but epidemiological evidence is limited. We aimed to explore the associations of total testosterone (TT), estradiol (E 2 ), and sex hormone binding globulin (SHBG) in children and adolescents with PFAS in 921 participants 6-19 years of age from NHANES 2013 to 2016. Multiple linear regression models and Bayesian Kernel Machine Regression (BKMR) models stratified by sex-age and sex-puberty-status groups were performed to explore the associations of the associations of individual or mixture of PFAS with sex hormone levels, respectively. Inverse associations were observed between n-PFOA and SHBG in female adolescents when the exposure was modeled as continuous (β = -0.20, 95% CI -0.33, -0.07) or categorized variable (P for trend = 0.005). In children, inverse associations were observed by BKMR in 6-11-year-old girls of high concentration, and in boys of low concentration of the PFAS mixture with TT. A positive association of PFAS mixture with SHBG was observed in boys. PFOS and PFNA were identified as major contributors to the associations in girls and boys, respectively. Although the 95% credible intervals included the null in adolescents, suggestive negative associations of PFAS mixture with TT and SHBG levels in adolescents aged 12-19 years were found by BKMR. Results by sex-puberty status presented a similar pattern, where significantly inverse associations between PFAS mixture and E 2 were observed in the pubertal. Our findings suggested the associations of either individual or mixture PFAS with decreased TT levels, and increased SHBG levels in U.S. children and adolescents, and with decreased E 2 levels in pubertal individuals. The associations were evident in children., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The toxic perfluorooctanoic acid (PFOA) is widely spread in terrestrial and aquatic habitats owing to its resistance to conventional degradation processes. Advanced techniques to degrade PFOA requires drastic conditions with high energy cost. In this study, we investigated PFOA biodegradation in a simple dual biocatalyzed microbial electrosynthesis system (MES). Different PFOA loadings (1, 5, and 10 ppm) were tested and a biodegradation of 91% was observed within 120 h. Propionate production improved and short-carbon-chain PFOA intermediates were detected, which confirmed PFOA biodegradation. However, the current density decreased, indicating an inhibitory effect of PFOA. High-throughput biofilm analysis revealed that PFOA regulated the microbial flora. Microbial community analysis showed enrichment of the more resilient and PFOA adaptive microbes, including Methanosarcina and Petrimonas. Our study promotes the potential use of dual biocatalyzed MES system as an environment-friendly and inexpensive method to remediate PFOA and provides a new direction for bioremediation research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Per- and polyfluoroalkyl substances (PFASs) and perfluoroalkyl ether carboxylic acids (PFECAs) are organic chemicals that are widely used in the manufacture of a wide range of human-made products. Many monitoring findings revealed the presence of PFASs and PFECAs in numerous environmental sources, including water, soil, and air, which drew more attention to both chemicals. Because of their unknown toxicity, the discovery of PFASs and PFECAs in a variety of environmental sources was viewed as a cause for concern. In the present study, male mice were given orally one of the typical PFASs, perfluorooctanoic acid (PFOA), and one of the representative PFECAs, hexafluoropropylene oxide-dimer acid (HFPO-DA). The liver index showing hepatomegaly rose significantly after 90 d of exposure to PFOA and HFPO-DA, respectively. While sharing similar suppressor genes, both chemicals demonstrated unique hepatotoxic mechanisms. In different ways, these two substances altered the expression of hepatic stress-sensing genes as well as the regulation of nuclear receptors. Not only are bile acid metabolism-related genes in the liver altered, but cholesterol metabolism-related genes as well. These results indicate that PFOA and HFPO-DA both cause hepatotoxicity and bile acid metabolism impairment with distinct mechanisms., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Perfluorooctanesulfonic acid (PFOS) has widely been reported to persist in the environment and to elicit neurotoxicological effects in wildlife and humans. Following the restriction of PFOS use, 6:2 chlorinated polyfluorinated ether sulfonate (F-53B) and sodium p-perfluorous nonenoxybenzene sulfonate (OBS) have emerged as novel PFOS alternatives and have been detected in the environment. However, knowledge on the toxicological effects of these alternatives remains scarce. Using developing transgenic Tg(dat:eGFP) zebrafish, we evaluated the consequences of exposure to 0, 0.1 and 1 mg/l PFOS, F-53B and OBS on the dopaminergic system, locomotor behaviour and mitochondrial function. All compounds generally reduced locomotor activity under light conditions irrespective of exposure concentration. Exposure to OBS (at all concentrations), as well as PFOS and F-53B (at 1 mg/l), significantly reduced subpallial dopaminergic neuron abundance. PFOS also significantly reduced dat and pink1 expression irrespective of exposure concentration, while F-53B and OBS tended to reduce mitochondrial pink1 and fis1 expression across concentrations without reaching statistical significance. Mitochondrial function, in the form of reduced oxygen consumption rate and marginally inhibited ATP-linked oxygen consumption rate, was affected only in response to 1 mg/l PFOS. Together, PFOS and the emerging contaminants F-53B and OBS inhibit locomotion at similar concentrations, a finding correlated with decreased dopaminergic neuron numbers in the subpallium and decreased expression of pink1. These findings are relevant to wildlife and human health, as they suggest that PFOS as well as replacement compounds affect locomotion likely in part by negatively impacting the dopamine system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Perfluorooctanoic acid (PFOA) and arsenic are widely distributed pollutants and can coexist in the environment. However, no study has been reported about the effects of different arsenic species on the joint toxicity of arsenic and PFOA to soil invertebrates. In this study, four arsenic species were selected, including arsenite (As(III)), arsenate (As(V)), monomethylarsonate (MMA), and dimethylarsinate (DMA). Earthworms Eisenia fetida were exposed to soils spiked with sublethal concentrations of PFOA, different arsenic species, and their binary mixtures for 56 days. The bioaccumulation and biotransformation of pollutants, as well as eight biomarkers in organisms, were assayed. The results indicated that the coexistence of PFOA and different arsenic species in soils could enhance the bioavailability of arsenic species while reducing the bioavailability of PFOA, and inhibit the arsenic biotransformation process in earthworms. Responses of most biomarkers in joint treatments of PFOA and As(III)/As(V) showed more significant variations compared with those in single treatments, indicating higher toxicity to the earthworms. The Integrated Biomarker Response (IBR) index was used to integrate the multi-biomarker responses, and the results also exhibited enhanced toxic effects in combined treatments of inorganic arsenic and PFOA. In comparison, both the biomarker variations and IBR values were lower in joint treatments of PFOA and MMA/DMA. Then the toxic interactions in the binary mixture systems were characterized by using a combined method of IBR and Effect Addition Index. The results revealed that the toxic interactions of the PFOA/arsenic mixture in earthworms depended on the different species of arsenic. The combined exposure of PFOA with inorganic arsenic led to a synergistic interaction, while that with organic arsenic resulted in an antagonistic response. Overall, this study provides new insights into the assessment of the joint toxicity of perfluoroalkyl substances and arsenic in soil ecosystems., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Amongst per- and polyfluoroalkyl substances (PFAS) compounds, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have a high persistence in physicochemical and biological degradation; therefore, the accumulation of PFOS and PFOA can negatively affect aquatic organisms and human health. In this study, two microalgae species ( Chlorella vulgaris and Scenedesmus obliquus ) were exposed to different concentrations of a PFOS and PFOA mixture (0 to 10 mg L -1 ). With increases in the contact time (days) and the PFAS concentration (mg L -1 ) from 1 to 7, and 0.5 to 10, respectively, the cell viability, total chlorophyll content, and protein content decreased, and the decrease in these parameters was significantly greater in Scenedesmus obliquus . As another step in the study, the response surface methodology (RSM) was used to optimize the toxicity effects of PFAS on microalgae in a logical way, as demonstrated by the high R 2 (>0.9). In another stage, a molecular docking study was performed to monitor the interaction of PFOS and PFOA with the microalgae, considering hydrolysis and the enzymes involved in oxidation-reduction reactions using individual enzymes. The analysis was conducted on carboxypeptidase in Chlorella vulgaris and on c-terminal processing protease and oxidized cytochrome c6 in Scenedesmus obliquus . For the enzyme activity, the affinity and dimensions of ligands-binding sites and ligand-binding energy were estimated in each case.

Perfluorooctanoic acid (PFOA) is a widespread persistent organic pollutant. Fertile chicken eggs were exposed to PFOA and incubated to hatch. At three time points post hatch (0-, 1- and 3-months old), chickens were subjected to electrocardiography and sacrificed. Serum was subjected to LC-MS/MS for PFOA concentration, and organs were subjected to histopathological assessments. Additionally, PPARα-silencing lentivirus was co-applied with PFOA exposure, and the corresponding phenotypes were evaluated. Western blotting was performed to assess expressions of FABPs and pSMAD2 in heart and liver samples. Considerable amount of PFOA were detected in hatchling chicken serum, but not in one-month-old or three-month-old chicken serum. PFOA exposure resulted in developmental cardiotoxicity and hepatotoxicity in hatchling chickens. Meanwhile, one-month-old chickens still exhibited elevated heart rate, but classical cardiac remodeling (thicker right ventricular wall) were observed in exposed animals. Three-month-old chickens exhibited similar results as one-month-old ones. PPARα silencing only had partial protective effects in hatchling chickens, but the protective effects seemed to increase as chickens aged. Western blotting results indicated that L-FABP was involved in PFOA-induced hepatotoxicity, while pSMAD2 was involved in PFOA-induced cardiotoxicity. In summary, developmental exposure to PFOA resulted in persistent cardiotoxicity, but not hepatotoxicity. PPARα participates in both cardiotoxicity and hepatotoxicity., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Qixiao Jiang reports financial support was provided by Shandong Province Natural Science Foundation. Junhua Yuan reports financial support was provided by National Natural Science Foundation of China., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Perfluorooctanoic acid (PFOA) could induce developmental toxicities, affecting various organs, including the heart. Although peroxisome-proliferation activated receptor alpha (PPARα) had been identified as a major target of PFOA, PPARα-independent effects are frequently reported. To further elucidate the mechanism of toxicity in PFOA-induced developmental cardiotoxicity, RNA-seq analysis was performed in hatchling chicken hearts developmentally exposed to vehicle or 2 mg/kg (egg weight) PFOA. RT-PCR and western blotting were then performed to confirm the identified potential targets. Furthermore, lentivirus was designed to overexpress and silence identified target miRNA in developing chicken embryo, and the resulting phenotypes were investigated. 21 miRNAs and 1142 mRNAs were identified to be affected by developmental exposure to PFOA in chicken embryo hearts. Among the identified differentially expressed miRNAs, miR-490-5p was confirmed to be significantly affected by PFOA exposure, along with its downstream targets, Synaptosome associated protein 91 (SNAP91) and LY6/PLAUR domain containing 6 (LYPD6), as indicated by RT-PCR and western blotting results. Lentivirus overexpressing miR-490-5p mimicked the phenotype induced by PFOA exposure, while lentivirus silencing miR-490-5p alleviated PFOA-induced changes. Similar patterns were also observed in the expression of downstream target genes, SNAP91 and LYPD6. In summary, miR-490-5p and its downstream genes, SNAP91 and LYPD6 are associated with PFOA-induced developmental cardiotoxicity in chicken embryo, which might help to further elucidate the mechanism of PFOA-induced developmental cardiotoxicity., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Qixiao Jiang reports financial support was provided by Shandong Province Natural Science Foundation. Junhua Yuan reports financial support was provided by National Natural Science Foundation of China., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Per- and polyfluoroalkyl substances (PFAS) are chemicals resistant to degradation. While such a feature is desirable in consumer and industrial products, some PFAS, including perfluorooctanoic acid (PFOA), are toxic and bioaccumulate. Hexafluoropropylene oxide dimer acid (HFPO-DA), an emerging PFAS developed to replace PFOA, has not been extensively studied. To evaluate the potential toxicity of HFPO-DA with a cost- and time-efficient approach, we exposed C. elegans larvae for 48 h to 4 × 10 -9 -4 g/L HFPO-DA in liquid media and measured developmental, behavioral, locomotor, and transcriptional effects at various exposure levels. Worms exposed to 1.5-4 g/L HFPO-DA were developmentally delayed, and progeny production was significantly delayed (p < 0.05) in worms exposed to 2-4 g/L HFPO-DA. Statistically significant differential gene expression was identified in all fourteen HFPO-DA exposure groups ranging from 1.25 × 10 -5 to 4 g/L, except for 6.25 × 10 -5 g/L. Among 10298 analyzed genes, 2624 differentially expressed genes (DEGs) were identified in the developmentally delayed 4 g/L group only, and 78 genes were differentially expressed in at least one of the thirteen groups testing 1.25 × 10 -5 -2 g/L HFPO-DA exposures. Genes encoding for detoxification enzymes including cytochrome P450 and UDP glucuronosyltransferases were upregulated in 0.25-4 g/L acute exposure groups. DEGs were also identified in lower exposure level groups, though they did not share biological functions except for six ribosomal protein-coding genes. While our transcriptional data is inconclusive to infer mechanisms of toxicity, the significant gene expression differences at 1.25 × 10 -5 g/L, the lowest concentration tested for transcriptional changes, calls for further targeted analyses of low-dose HFPO-DA exposure effects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Perfluorooctanoic acid (PFOA) is abundant in environment due to its historical uses in consumer products and industrial applications. Exposure to low doses of PFOA has been associated with various disease risks, including neurological disorders. The underlying mechanism, however, remains poorly understood. In this study, we examined the effects of low dose PFOA exposure at 0.4 and 4 μg/L on the morphology, epigenome, mitochondrion, and neuronal markers of dopaminergic (DA)-like SH-SY5Y cells. We observed persistent decreases in H3K4me3, H3K27me3 and 5 mC markers in nucleus along with alterations in nuclear size and chromatin compaction percentage in DA-like neurons differentiated from SH-SY5Y cells exposed to 0.4 and 4 μg/L PFOA. Among the selected epigenetic features, DNA methylation pattern can be used to distinguish between PFOA-exposed and naïve populations, suggesting the involvement of epigenetic regulation. Moreover, DA-like neurons with pre-differentiation PFOA exposure exhibit altered network connectivity, mitochondrial volume, and TH expression, implying impairment in DA neuron functionality. Collectively, our results revealed the prolonged effects of developmental PFOA exposure on the fitness of DA-like neurons and identified epigenome and mitochondrion as potential targets for bearing long-lasting changes contributing to increased risks of neurological diseases later in life., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

It has been reported that exposure to perfluorooctane sulfonates (PFOS) causes behavioral abnormalities in zebrafish larvae, but the possible mechanisms underlying these changes remain unexplored. In this study, zebrafish embryos (2 h postfertilization, 2-hpf) were exposed to PFOS at different concentrations (0, 0.032, 0.32 and 3.2 mg/L) for 120 h. Developmental endpoints and the locomotion behavior of larvae were evaluated. Reactive oxygen species (ROS) levels, dopamine contents, several genes and proteins related to neurodevelopment and dopamine signaling were examined. Our results indicate that increased ROS levels in the zebrafish larvae heads may be causally associated with neurodevelopment damage. Meanwhile, brain-derived neurotrophic factor (BDNF) and alpha1-Tubulin (α1-Tubulin) protein contents were significantly increased, which may be a compensatory mechanism for the impaired central nervous system. PFOS-induced locomotor hyperactivity was observed in the first light phase and dark phase at the 0.32 and 3.2 mg/L of PFOS. Upregulation of dopamine-related genes tyrosine hydroxylase (th) and dopamine transporter (dat) associated with increased dopamine contents in the 3.2 mg/L of PFOS. In addition, protein expression of TH and DAT were noted at the 0.32 and 3.2 mg/L of PFOS concentrations. Our results suggested that PFOS induces neurobehavioral changes in zebrafish larvae, possibly by perturbing a dopamine signaling pathway. In addition, PFOS induced development damage, such as increased malformation rate and shorter body length., (Copyright © 2022 Elsevier Ltd. All rights reserved.)