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Per- and polyfluoroalkyl substances (PFASs), especially as emerging compounds, have been widely detected in coastal seawater. However, the awareness of the interaction between PFASs at environmental concentrations and marine diatoms is still limited. In this study, Skeletonema costatum was exposed to three co-existing PFASs, namely hexafluoropropylene oxide dimer acid (HFPO-DA), 6 : 2 chlorinated polyfluorinated ether sulfonate (Cl-PFAES), and perfluoroethylcyclohexane sulfonate (PFECHS) (15-300 ng L -1 in total), for 14 days. In the 300 ng L -1 test group, the significant down-regulation of chlorophyllide a in porphyrin metabolism, light-harvesting capacity and carbon fixation were the main inhibitory mechanisms of photosynthesis by emerging PFASs at the 14th day compared to the 8th day, which indicated that they may have a shading effect on S. costatum . Additionally, mixed PFASs could also activate nicotinamide adenine dinucleotide phosphate (NADPH) oxidase by up-regulating gene gp91 and down-regulating genes CaM4 and NDPK2 to generate excessive ROS. This resulted in a decrease in the algal biomass, which would further weaken the primary productivity of S. costatum . Our findings illustrated that mixed emerging PFASs at environmental concentrations may interfere with the carbon balance of marine diatoms.

In this study, various crops and farmland soils were collected from the Fen-Wei Plain, China, to investigate the bioavailability of perfluoroalkyl substances (PFAS), their accumulation in edible plant tissues, and the factors impacting their accumulation. PFAS were frequently detected in all of the crops, with total concentrations ranging from 0.61 to 35.8 ng/g. The results of sequential extractions with water, basic methanol, and acidic methanol indicate that water extraction enables to characterize the bioavailability of PFAS in soil to edible plant tissues more accurately, especially for the shorter-chain homologues. The bioavailability of PFAS was remarkably enhanced in the rhizosphere (RS) soil, with the strongest effect observed for leafy vegetables. The water-extracted Σ 16 PFAS in RS soil was strongly correlated with the content of dissolved organic carbon in the soil. Tannins and lignin, identified as the main components of plant root exudates by Fourier transform-ion cyclotron resonance mass spectrometry, were found to enhance the bioavailability of PFAS significantly. Redundancy analysis provided strong evidence that the lipid and protein contents in edible plant tissues play important roles in the accumulation of short- and long-chain PFAS, respectively. Additionally, the high water demand of these tissues during the growth stage greatly facilitated the translocation of PFAS, particularly for the short-chain homologues and perfluorooctanoic acid.

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.)

Numerous US drinking water aquifers have been contaminated with per- and polyfluoroalkyl substances (PFAS) from fire-fighting and fire-training activities using aqueous film-forming foam (AFFF). These sites often contain other organic compounds, such as fuel hydrocarbons and methane, which may serve as primary substrates for cometabolic (i.e., nongrowth-linked) biotransformation reactions. This work investigates the abilities of AFFF site relevant bacteria (methanotrophs, propanotrophs, octane, pentane, isobutane, toluene, and ammonia oxidizers), known to express oxygenase enzymes when degrading their primary substrates, to biotransform perfluoroalkyl acid (PFAA) precursors to terminal PFAAs. Microcosms containing AFFF-impacted groundwater, 6:2 fluorotelomer sulfonate (6:2 FTS), or N -ethylperfluorooctane sulfonamidoethanol (EtFOSE) were inoculated with the aerobic cultures above and incubated for 4 and 8 weeks at 22 °C. Bottles were sacrificed, extracted, and subjected to target, nontarget, and suspect screening for PFAS. The PFAA precursors 6:2 FTS, N-sulfopropyldimethyl ammoniopropyl perfluorohexane sulfonamide (SPrAmPr-FHxSA), and EtFOSE transformed up to 99, 71, and 93%, respectively, and relevant daughter products, such as the 6:1 fluorotelomer ketone sulfonate (6:1 FTKS), were identified in quantities previously not observed, implicating oxygenase enzymes. This is the first report of a suite of site relevant PFAA precursors being transformed in AFFF-impacted groundwater by bacteria grown on substrates known to induce specific oxygenase enzymes. The data provide crucial insights into the microbial transformation of these compounds in the subsurface.

Short-chained perfluoroalkyl acids (PFAAs, C n F 2n+1 -R, n ≤ 6) have merged as global concerns due to their extensive application and considerable toxicity. However, long-chained PFAAs (n ≥ 7) featured with high persistence are still ubiquitously observed in aquatic environment. To understand the uptake behavior of short-chained PFAAs in aquatic macrophytes, the uptake kinetics, bioconcentration, and translocation of short-chained PFAAs (3 ≤n ≤ 6) in two typical free-floating macrophytes (Eichhornia crassipes and Ceratophyllum demersum) were investigated in the treatments with and without long-chained PFAAs (7 ≤n ≤ 11). Results showed that short-chained PFAAs can be readily accumulated in both E. crassipes and C. demersum, and the uptake of short-chained PFAAs fit the two-compartment kinetic model well (p < 0.05). In the treatments with long-chained PFAAs, significant concentration decreases of all concerned short-chained PFAAs in E. crassipes and PFAAs with n ≤ 5 in C. demersum were observed. Long-chained PFAAs could hinder the uptake rates, bioconcentration factors, and translocation factors of most short-chained PFAAs in free-floating macrophytes (p < 0.01). Significant correlations between bioconcentration factors and perfluoroalkyl chain length were only observed when long-chained PFAAs were considered (p < 0.01). Our results underlined that the effects of long-chained PFAAs should be taken into consideration in understanding the uptake and bioaccumulation behaviors of short-chained PFAAs., Competing Interests: Declaration of Competing Interest The authors have declared that no conflict of interest exists., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Limited information is available on the removal of per- and polyfluoroalkyl substances (PFAS) in anaerobic digestion (AD). Τhe fate of six PFAS was studied in thermophilic bioreactors in the presence of granular activated carbon (GAC) and voltage application. Reactors with GAC exhibited lower concentrations of volatile fatty acids and higher methane production compared to those with and without the application of voltage. Analysis of PFAS in dissolved and solid phase showed that their distribution was dependent on perfluorocarbon chain length and functional group. Mass balances showed that PFAS were not removed during conventional AD or after applying voltage; however, significant removal (up to 61 ± 8 %) was observed in bioreactors with GAC for perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorooctane sulfonate (PFOS). Biomass characterization showed that in these bioreactors, the relative abundance of Acinetobacter and Pseudomonas was higher, indicating their potential role in PFAS biotransformation., 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. Published by Elsevier Ltd.)

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.)

Exposure to per- and polyfluoroalkyl substances (PFAS) has been associated with toxicity in wildlife and negative health effects in humans. Decades of fire training activity at Joint Base Cape Cod (MA, USA) incorporated the use of aqueous film-forming foam (AFFF), which resulted in long-term PFAS contamination of sediments, groundwater, and hydrologically connected surface waters. To explore the bioconcentration potential of PFAS in complex environmental mixtures, a mobile laboratory was established to evaluate the bioconcentration of PFAS from AFFF-impacted groundwater by flow-through design. Fathead minnows (n = 24) were exposed to PFAS in groundwater over a 21-day period and tissue-specific PFAS burdens in liver, kidney, and gonad were derived at three different time points. The ∑PFAS concentrations in groundwater increased from approximately 10,000 ng/L at day 1 to 36,000 ng/L at day 21. The relative abundance of PFAS in liver, kidney, and gonad shifted temporally from majority perfluoroalkyl sulfonamides (FASAs) to perfluoroalkyl sulfonates (PFSAs). By day 21, mean ∑PFAS concentrations in tissues displayed a predominance in the order of liver > kidney > gonad. Generally, bioconcentration factors (BCFs) for FASAs, perfluoroalkyl carboxylates (PFCAs), and fluorotelomer sulfonates (FTS) increased with degree of fluorinated carbon chain length, but this was not evident for PFSAs. Perfluorooctane sulfonamide (FOSA) displayed the highest mean BCF (8700 L/kg) in day 21 kidney. Suspect screening results revealed the presence of several perfluoroalkyl sulfinate and FASA compounds present in groundwater and in liver for which pseudo-bioconcentration factors are also reported. The bioconcentration observed for precursor compounds and PFSA derivatives detected suggests alternative pathways for terminal PFAS exposure in aquatic wildlife and humans. Environ Toxicol Chem 2024;43:1795-1806. © 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC., (© 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.)

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.

Given environmental persistence, potential for bioaccumulation, and toxicity of Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), the scientific community has increasingly focused on researching their toxicology and degradation methods. This paper presents a survey of recent research advances in the toxicological effects and degradation methods of PFOA and PFOS. Their adverse effects on the liver, nervous system, male reproductive system, genetics, and development are detailed. Additionally, the degradation techniques of PFOA and PFOS, including photochemical, photocatalytic, and electrochemical methods, are analyzed and compared, highlighted the potential of these technologies for environmental remediation. The biotransformation pathways and mechanisms of PFOA and PFOS involving microorganisms, plants, and enzymes are also presented. As the primary green degradation pathway for PFOA and PFOS, Biodegradation uses specific microorganisms, plants or enzymes to remove PFOA and PFOS from the environment through redox reactions, enzyme catalysis and other pathways. Currently, there has been a paucity of research conducted on the biodegradation of PFOA and PFOS. However, this degradation technology is promising owing to its specificity, cost-effectiveness, and ease of implementation. Furthermore, novel materials/methods for PFOA and PFOS degradation are presented in this paper. These novel materials/methods effectively improve the degradation efficiency of PFOA and PFOS and provide new ideas and tools for the degradation of PFOA and PFOS. This information can assist researchers in identifying flaws and gaps in the field, which can facilitate the formulation of innovative research ideas., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

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.

Seabirds are often considered sentinel species of marine ecosystems, and their blood and eggs utilized to monitor local environmental contaminations. Most seabirds breeding in the Arctic are migratory and thus are exposed to geographically distinct sources of contamination throughout the year, including per- and polyfluoroalkyl substances (PFAS). Despite the abundance and high toxicity of PFAS, little is known about whether blood concentrations at breeding sites reliably reflect local contamination or exposure in distant wintering areas. We tested this by combining movement tracking data and PFAS analysis (nine compounds) from the blood of prelaying black-legged kittiwakes ( Rissa tridactyla ) nesting in Arctic Norway (Svalbard). PFAS burden before egg laying varied with the latitude of the wintering area and was negatively associated with time upon return of individuals at the Arctic nesting site. Kittiwakes ( n = 64) wintering farther south carried lighter burdens of shorter-chain perfluoroalkyl carboxylates (PFCAs, C 9 -C 12 ) and heavier burdens of longer chain PFCAs (C 13 -C 14 ) and perfluorooctanesulfonic acid compared to those wintering farther north. Thus, blood concentrations prior to egg laying still reflected the uptake during the previous wintering stage, suggesting that migratory seabirds can act as biovectors of PFAS to Arctic nesting sites.

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.

Enterohepatic circulation has been reported to play a significant role in the bioaccumulation of PFASs. In this study, the tissue distribution and excretion of PFOS and its alternatives, namely 6:2 and 8:2 fluorotelomer sulfonic acid (FTSA) was investigated using a mouse assay with a focus on role of enterohepatic circulation. Liver was the primarily accumulating organ for PFOS and 8:2 FTSA (33.4 % and 25.8 % of total doses absorbed after 14 days), whereas 65 % of 6:2 FTSA was excreted via urine within 24 h. Peak levels of 8:2 FTSA and PFOS were found in the gallbladder, implying the important role of enterohepatic circulation in PFASs reabsorption. The role of enterohepatic circulation was further evaluated through co-exposure of 8:2 FTSA and PFOS with medicines (namely metformin (MET) and ursodeoxycholic acid (UDCA)). MET reduced accumulation of 8:2 FTSA and PFOS in the liver by 68.6 % and 65.8 %, through down-regulation of bile acid transporter (Asbt) and enhancement of fecal excretion. Conversely, UDCA raised their concentrations by 21.9 % and 34.6 % compared to that exposed solely to PFASs. A strong positive correlation was identified between PFASs serum levels and Asbt expression. This study illuminated PFAS bioaccumulation mechanisms and suggested potential strategies to mitigate the exposure 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 B.V. All rights reserved.)

In the evolving field of drug discovery and development, multiorgans-on-a-chip and microphysiological systems are gaining popularity owing to their ability to emulate in vivo biological environments. Among the various gut-liver-on-a-chip systems for studying oral drug absorption, the chip developed in this study stands out with two distinct features: incorporation of perfluoropolyether (PFPE) to effectively mitigate drug sorption and a unique enterohepatic single-passage system, which simplifies the analysis of first-pass metabolism and oral bioavailability. By introducing a bolus drug injection into the liver compartment, hepatic extraction alone could be evaluated, further enhancing our estimation of intestinal availability. In a study on midazolam (MDZ), PFPE-based chips showed more than 20-times the appearance of intact MDZ in the liver compartment effluent compared to PDMS-based counterparts. Notably, saturation of hepatic metabolism at higher concentrations was confirmed by observations when the dose was reduced from 200 μM to 10 μM. This result was further emphasized when the metabolism was significantly inhibited by the coadministration of ketoconazole. Our chip, which is designed to minimize the dead volume between the gut and liver compartments, is adept at sensitively observing the saturation of metabolism and the effect of inhibitors. Using genome-edited CYP3A4/UGT1A1-expressing Caco-2 cells, the estimates for intestinal and hepatic availabilities were 0.96 and 0.82, respectively; these values are higher than the known human in vivo values. Although the metabolic activity in each compartment can be further improved, this gut-liver-on-a-chip can not only be used to evaluate oral bioavailability but also to carry out individual assessment of both intestinal and hepatic availability.

PFAS (poly- and per-fluorinated alkyl substances) represent a large family of recalcitrant organic compounds that are widely used and pose serious threats to human and ecosystem health. Here, palladium (Pd 0 )-catalyzed defluorination and microbiological mineralization were combined in a denitrifying H 2 -based membrane biofilm reactor to remove co-occurring perfluorooctanoic acid (PFOA) and nitrate. The combined process, i.e., Pd-biofilm, enabled continuous removal of ∼4 mmol/L nitrate and ∼1 mg/L PFOA, with 81% defluorination of PFOA. Metagenome analysis identified bacteria likely responsible for biodegradation of partially defluorinated PFOA: Dechloromonas sp. CZR5, Kaistella koreensis , Ochrobacterum anthropic , and Azospira sp. I13. High-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and metagenome analyses revealed that the presence of nitrate promoted microbiological oxidation of partially defluorinated PFOA. Taken together, the results point to PFOA-oxidation pathways that began with PFOA adsorption to Pd 0 , which enabled catalytic generation of partially or fully defluorinated fatty acids and stepwise oxidation and defluorination by the bacteria. This study documents how combining catalysis and microbiological transformation enables the simultaneous removal of PFOA and nitrate.

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.)

Perfluorooctane sulfonate (PFOS), one of the most frequently detected per- and polyfluoroalkyl substances (PFAS) occurring in soil, surface water, and groundwater near sites contaminated with aqueous film-forming foam (AFFF), has proven to be recalcitrant to many destructive remedies, including chemical oxidation. We investigated the potential to utilize microbially mediated reduction (bioreduction) to degrade PFOS and other PFAS through addition of a known dehalogenating culture, WBC-2, to soil obtained from an AFFF-contaminated site. A substantial decrease in total mass of PFOS (soil and water) was observed in microcosms amended with WBC-2 and chlorinated volatile organic compound (cVOC) co-contaminants - 46.4 ± 11.0 % removal of PFOS over the 45-day experiment. In contrast, perfluorooctanoate (PFOA) and 6:2 fluorotelomer sulfonate (6:2 FTS) concentrations did not decrease in the same microcosms. The low or non-detectable concentrations of potential metabolites in full PFAS analyses, including after application of the total oxidizable precursor assay, indicated that defluorination occurred to non-fluorinated compounds or ultrashort-chain PFAS. Nevertheless, additional research on the metabolites and degradation pathways is needed. Population abundances of known dehalorespirers did not change with PFOS removal during the experiment, making their association with PFOS removal unclear. An increased abundance of sulfate reducers in the genus Desulfosporosinus (Firmicutes) and Sulfurospirillum (Campilobacterota) was observed with PFOS removal, most likely linked to initiation of biodegradation by desulfonation. These results have important implications for development of in situ bioremediation methods for PFAS and advancing knowledge of natural attenuation processes., 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., (Published by Elsevier B.V.)

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.)

Due to the wastewater irrigation or biosolid application, per- and polyfluoroalkyl substances (PFASs) have been widely detected in agriculture soil and hence crops or vegetables. Consumption of contaminated crops and vegetables is considered as an important route of human exposure to PFASs. Machine learning (ML) models have been developed to predict PFAS uptake by plants with majority focus on roots. However, ML models for predicting accumulation of PFASs in above ground edible tissues have yet to be investigated. In this study, 811 data points covering 22 PFASs represented by molecular fingerprints and 5 plant categories (namely the root class, leaf class, cereals, legumes, and fruits) were used for model development. The Extreme Gradient Boosting (XGB) model demonstrated the most favorable performance to predict the bioaccumulation factors (BAFs) in all the 4 plant tissues (namely root, leaf, stem, and fruit) achieving coefficients of determination R 2 as 0.82-0.93. Feature importance analysis showed that the top influential factors for BAFs varied among different plant tissues, indicating that model developed for root concentration prediction may not be feasible for above ground parts. The XGB model's performance was further demonstrated by comparing with data from pot experiments measuring BAFs of 12 PFASs in lettuce. The correlation between predicted and measured results was favorable for BAFs in both lettuce roots and leaves with R 2 values of 0.76 and 0.81. This study developed a robust approach to comprehensively understand the uptake of PFASs in both plant roots and above ground parts, offering key insights into PFAS risk assessment and food safety., 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 B.V. All rights reserved.)

Crop contamination of perfluoroalkyl substances (PFASs) may threaten human health, with root and leaves representing the primary uptake pathways of PFASs in crops. Therefore, it is imperative to elucidate the uptake characteristics of PFASs by crop roots and leaves as well as the critical influencing factors. In this study, the uptake and translocation of PFASs by roots and leaves of pak choi and radish were systematically explored based on perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA), and perfluorooctane sulfonate (PFOS). Additionally, the roles of root Casparian strips, leaf stomata, and PFAS structures in the aforementioned processes were elucidated. Compared with pak choi, PFASs are more easily transferred to leaves after root uptake in radish, resulting from the lack of root Casparian strips. In pak choi root, the bioaccumulation of C4-C8 perfluoroalkyl carboxylic acids (PFCAs) showed a U-shaped trend with the increase of their carbon chain lengths, and the translocation potentials of individual PFASs from root to leaves negatively correlated with their chain lengths. The leaf uptake of PFOA in pak choi and radish mainly depended on cuticle sorption, with the evidence of a slight decrease in the concentrations of PFOA in exposed leaves after stomatal closure induced by abscisic acid. The leaf bioaccumulation of C4-C8 PFCAs in pak choi exhibited an inverted U-shaped trend as their carbon chain lengths increased. PFASs in exposed leaves can be translocated to the root and then re-transferred to unexposed leaves in vegetables. The longer-chain PFASs showed higher translocation potentials from exposed leaves to root. PFOS demonstrated a higher bioaccumulation than PFOA in crop roots and leaves, mainly due to the greater hydrophobicity of PFOS. Planting root vegetables lacking Casparian strips is inadvisable in PFAS-contaminated environments, in view of their higher PFAS bioaccumulation and considerable human intake., 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 B.V. All rights reserved.)

The potential ecological risk of per- and polyfluorinated alkyl substances (PFASs) in phytoremediation has raised social concerns, promoting a need to better understand their distribution and risks in the recovery process of aquatic plants. Herein, we aim to fill this knowledge gap by investigating the distribution and ecotoxicological effects of PFASs on the structure and function of water-macrophyte-sediment microcosm systems. Among the entire system, 63.0 %-73.1 % PFOA was found in sediments and submerged plants, however, 52.5 %-53.0 % of PFPeA and 47.0 %-47.5 % of PFBS remained in the water under different treatments. PFOA was more bioavailable than the other substances, as demonstrated by the bioaccumulation factors (BAF) with ranges exposed to PFPeA and PFBS. Bioaccumulation PFASs induced plant oxidative stress which generates enzymes to suppress superoxide, and disturbed the processes of lysine biosynthesis, in which allysine, meso-2,6-diaminoheptanedioate, and Nsuccinyl-2-amino-6-ketopimelate were downregulated. PFASs were detected in the propagator (turions) of an ecological restoration species, where short-chain PFASs (70.1 % and 45.7 % for 2 or 20 μg/L PFAS exposure, respectively) were found to spread further into new individuals and profoundly influence ecological processes shaping populations. PFASs significantly enhanced the number of microbial species in the sediment, but the degree of differentiation in the microbial community structure was not significantly different. This study enhances our understanding of the ecological mechanisms of PFASs in the water-macrophyte-sediment systems and potential threats to the recovery process of macrophytes., Competing Interests: Declaration of competing interest All authors declared no potential conflicts of interest with respect to the publication of this research work., (Copyright © 2024. Published by Elsevier B.V.)

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.)

The behavior and fate of PFOS (perfluorooctanesulfonate) in the aquatic environment have received great attention due to its high toxicity and persistence. The nanoscale supramolecular mechanisms of interaction between PFOS and ubiquitous EPS (exopolymers) remain unclear though EPS have been widely-known to influence the bioavailability of PFOS. Typically, the exposure patterns of PFOS in aquatic animals changed with the EPS-PFOS interaction are not fully understood. This study hypothesized that PFOS exposure and accumulation pathways depended on the PFOS-EPS interactive assembly behavior and animal species. Two model animals, zebrafish and chironomid larvae, with different feeding habitats were chosen for the exposure and accumulation tests at the environmental concentrations of PFOS in the absence and presence of EPS. It was found that PFOS triggered the self-assembly of EPS to form large aggregates which significantly trapped PFOS. PFOS accumulation was significantly promoted in zebrafish but drastically reduced in chironomid larvae because of the nanoscale interactive assembly between EPS and PFOS. The decreased dermal uptake but increased oral uptake of PFOS by zebrafish with large mouthpart size could be ascribed to the increased ingestion of PFOS-enriched EPS aggregates as food. For the chironomid larvae with small mouthpart size, the PFOS-EPS assemblies reduced the dermal, oral and intestinal uptake of PFOS. The nano-visualization evidences confirmed that the PFOS-enriched EPS-PFOS assemblies blocked PFOS penetration through skin of both animals. These findings provide novel knowledge about the ecological risk of PFOS in aquatic environments., 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 B.V. All rights reserved.)

Per- and polyfluoroalkyl substances (PFAS) are recalcitrant synthetic organohalides known to negatively impact human health. Short-chain fluorotelomer alcohols are considered the precursor of various perfluorocarboxylic acids (PFCAs) in the environment. Their ongoing production and widespread detection motivate investigations of their biological transformation. Dietzia aurantiaca strain J3 was isolated from PFAS-contaminated landfill leachate using 6:2 fluorotelomer sulphonate (6:2 FTS) as a sulphur source. Resting cell experiments were used to test if strain J3 could transform fluorotelomer alcohols (6:2 and 4:2 FTOH). Strain J3 transformed fluorotelomer alcohols into PFCAs, polyfluorocarboxylic acids and transient intermediates. Over 6 days, 80 % and 58 % of 6:2 FTOH (0.1 mM) and 4:2 FTOH (0.12 mM) were degraded with 6.4 % and 14 % fluoride recovery respectively. Fluorotelomer unsaturated carboxylic acid (6:2 FTUCA) was the most abundant metabolite, accounting for 21 to 30 mol% of 6:2 FTOH (0.015 mM) applied on day zero. Glutathione (GSH) conjugates of 6:2/4:2 FTOH and 5:3 FTCA adducts were also structurally identified. Proteomics studies conducted to identify enzymes in the biotransformation pathway have revealed the role of various enzymes involved in β oxidation. This is the first report of 6:2/4:2 FTOH glutathione conjugates and 5:3 FTCA adducts in prokaryotes, and the first study to explore the biotransformation of 4:2 FTOH by pure bacterial strain., 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 B.V. 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).)

Per- and polyfluoroalkyl substances (PFAS) strongly bind to proteins and lipids in blood, which govern their accumulation and distribution in organisms. Understanding the plasma binding mechanism and species differences will facilitate the quantitative in vitro -to- in vivo extrapolation and improve risk assessment of PFAS. We studied the binding mechanism of 16 PFAS to bovine serum albumin (BSA), trout, and human plasma using solid-phase microextraction. Binding of anionic PFAS to BSA and human plasma was found to be highly concentration-dependent, while trout plasma binding was linear for the majority of the tested PFAS. At a molar ratio of PFAS to protein ν < 0.1 mol PFAS /mol protein , the specific protein binding of anionic PFAS dominated their human plasma binding. This would be the scenario for physiological conditions (ν < 0.01), whereas in in vitro assays, PFAS are often dosed in excess (ν > 1) and nonspecific binding becomes dominant. BSA was shown to serve as a good surrogate for human plasma. As trout plasma contains more lipids, the nonspecific binding to lipids affected the affinities of PFAS for trout plasma. Mass balance models that are parameterized with the protein-water and lipid-water partitioning constants (chemical characteristics), as well as the protein and lipid contents of the plasma (species characteristics), were successfully used to predict the binding to human and trout plasma.

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.)

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

Per- and polyfluoroalkyl substances (PFAS) are known for their high environmental persistence and potential toxicity. The presence of PFAS has been reported in many dairy products. However, the mechanisms underlying the accumulation of PFAS in these products remain unclear. Here, we used native mass spectrometry and molecular dynamics simulations to probe the interactions between 19 PFAS of environmental concern and two isoforms of the major bovine whey protein β-lactoglobulin (β-LG). We observed that six of these PFAS bound to both protein isoforms with low- to mid-micromolar dissociation constants. Based on quantitative, competitive binding experiments with endogenous ligands, PFAS can bind orthosterically and preferentially to β-LG's hydrophobic ligand-binding calyx. β-Cyclodextrin can also suppress binding of PFAS to β-LG owing to the ability of β-cyclodextrin to directly sequester PFAS from solution. This research sheds light on PFAS-β-LG binding, suggesting that such interactions could impact lipid-fatty acid transport in bovine mammary glands at high PFAS concentrations. Furthermore, our results highlight the potential use of β-cyclodextrin in mitigating PFAS binding, providing insights toward the development of strategies to reduce PFAS accumulation in dairy products and other biological systems.

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.)

Composting municipal food waste is a key strategy for beneficially reusing methane-producing waste that would otherwise occupy landfill space. However, land-applied compost can cycle per- and polyfluoroalkyl substances (PFAS) back into the food supply and the environment. We partnered with a pilot-scale windrow composting facility to investigate the sources and fate of 40 PFAS in food waste compost. A comparison of feedstock materials yielded concentrations of ∑PFAS under 1 ng g -1 in mulch and food waste and at 1380 ng g -1 in leachate from used compostable food contact materials. Concentrations of targeted ∑PFAS increased with compost maturity along the windrow (1.85-23.1 ng g -1 ) and in mature stockpiles of increasing curing age (12.6-84.3 ng g -1 ). Among 15 PFAS quantified in compost, short-chain perfluorocarboxylic acids (PFCAs) - C5 and C6 PFCAs in particular - led the increasing trend, suggesting biotransformation of precursor PFAS into these terminal PFAS through aerobic decomposition. Several precursor PFAS were also measured, including fluorotelomer carboxylic acids (FTCAs) and polyfluorinated phosphate diesters (PAPs). However, since most targeted analytical methods and proposed regulations prioritize terminal PFAS, testing fully matured compost would provide the most relevant snapshot of PFAS that could be land applied. In addition, removing co-disposed food contact materials from the FW feedstock onsite yielded only a 37 % reduction of PFAS loads in subsequent compost, likely due to PFAS leaching during co-disposal. Source-separation of food contact materials is currently the best management practice for meaningful reduction of PFAS in food waste composts intended for land application., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: John A. Bowden reports financial support was provided by US Environmental Protection Agency. John A. Bowden reports financial support was provided by Hinkley Center for Solid and Hazardous Waste Management. Timothy G. Townsend reports financial support was provided by US Environmental Protection Agency. Timothy G. Townsend reports financial support was provided by Hinkley Center for Solid and Hazardous Waste Management. Co-author Stephan Barron is the owner and operator of the composting facility from which samples for this study were collected. We felt that it was important to include Stephan as a co-author because he had to facilitate our access to sample collection and provide information about his composting process, which was then incorporated into the manuscript. Stephan was not involved in any way in sample processing, data analysis and interpretation, or manuscript writing. 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 Elsevier Ltd. All rights reserved.)

To address time-consuming and efficiency-limited challenges in conventional zero-valent iron (ZVI, Fe 0 ) reduction or biotransformation for perfluorooctanoic acid (PFOA) treatment, two calcium alginate-embedded amendments (biochar-immobilized PFOA-degrading bacteria (CB) and ZVI (CZ)) were developed to construct microbe-Fe 0 high-rate interaction systems. Interaction mechanisms and key metabolic pathways were systematically explored using metagenomics and a multi-process coupling model for PFOA under microbe-Fe 0 interaction. Compared to Fe 0 (0.0076 day -1 ) or microbe (0.0172 day -1 ) systems, the PFOA removal rate (0.0426 day -1 ) increased by 1.5 to 4.6 folds in the batch microbe-Fe 0 interaction system. Moreover, Pseudomonas accelerated the transformation of Fe 0 into Fe 3+ , which profoundly impacted PFOA transport and fate. Model results demonstrated microbe-Fe 0 interaction improved retardation effect for PFOA in columns, with decreased dispersivity a (0.48 to 0.20 cm), increased reaction rate λ (0.15 to 0.22 h -1 ), distribution coefficient K d (0.22 to 0.46 cm 3 ∙g -1 ), and fraction f´(52 % to 60 %) of first-order kinetic sorption of PFOA in microbe-Fe 0 interaction column system. Moreover, intermediates analysis showed that microbe-Fe 0 interaction diversified PFOA reaction pathways. Three key metabolic pathways (ko00362, ko00626, ko00361), eight functional genes, and corresponding enzymes for PFOA degradation were identified. These findings provide insights into microbe-Fe 0 "neural network-type" interaction by unveiling biotransformation and mineral transformation mechanisms for efficient PFOA treatment., 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 B.V. All rights reserved.)

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.)

Microplastics (MPs) and perfluorinated compounds (PFAS) are widespread in the global ecosystem. MPs have the ability to adsorb organic contaminants such as perfluorooctane sulfonate (PFOS), leading to combined effects. The current work aims to explore the individual and combined toxicological effects of polystyrene (PS) and PFOS on the growth and nerves of the freshwater planarian (Dugesia japonica). The results showed that PS particles could adsorb PFOS. PS and PFOS impeded the regeneration of decapitated planarians eyespots, whereas the combined treatment increased the locomotor speed of intact planarians. PS and PFOS caused significant DNA damage, while co-treatment with different PS concentrations aggravated and attenuated DNA damage, respectively. Further studies at the molecular level have shown that PS and PFOS affect the proliferation and differentiation of neoblasts in both intact and regenerating planarians, alter the expression levels of neuronal genes, and impede the development of the nervous system. PS and PFOS not only disrupted the homeostasis of intact planarians, but also inhibited the regeneration of decapitated planarians. This study is the first to assess the multiple toxicity of PS and PFOS to planarians after combined exposure. It provides a basis for the environmental and human health risks of MPs and PFAS., 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 B.V. All rights reserved.)

Per- and polyfluoroalkyl substances (PFAS) are persistent, bioaccumulative, and toxic synthetic chemicals of concern, which have been detected in nearly all environmental compartments. The present study provides a data analysis on PFAS concentrations in the Dutch inland and coastal national waters and fish sampled from 2008 to 2022 and 2015 to 2022, respectively. Although the fish database is relatively small, the water database is unique because of its temporal dimension. It appears that PFAS are omnipresent in Dutch water and fish, with relatively small spatial differences in absolute and relative concentrations (fingerprints) and few obvious temporal trends. Only perfluorooctanoic acid and perfluorooctanesulfonic acid (PFOS) aqueous concentrations in the rivers Rhine and Scheldt have substantially decreased since 2012. Still, PFOS concentrations exceed the European water quality standards at all and fish standards at many locations. Masses of PFAS entering the country and the North Sea are roughly 3.5 tonnes/year. Generally, the data suggest that most PFAS enter the Dutch aquatic environment predominantly through diffuse sources, yet several major point sources of specific PFAS were identified using fingerprints and monthly concentration profiles as identification tools. Finally, combining concentrations in fish and water, 265 bioaccumulation factors were derived, showing no statistically significant differences between freshwater and marine fish. Overall, the analysis provides new insights into PFAS bioaccumulation and spatiotemporal trends, mass discharges, and sources in The Netherlands. Environ Toxicol Chem 2024;43:965-975. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC., (© 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.)

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.)

Grown evidence has shown that the liver and reproductive organs were the main target organs of perfluorooctanoic acid (PFOA). Herein, we studied a toxic mechanism of PFOA using HeLa Chang liver epithelial cells. When incubated with PFOA for 24 h or 48 h, cell proliferation was inhibited in a concentration- and time-dependent fashion, but interestingly, the feature of dead cells was not notable. Mitochondrial volume was increased with concentration and time, whereas the mitochondrial membrane potential and produced ATP amounts were significantly reduced. Autophagosome-like vacuoles and contraction of the mitochondrial inner membrane were observed in PFOA-treated cells. The expression of acetyl CoA carboxylase (ACC) and p-ACC proteins rapidly decreased, and that of mitochondrial dynamics-related proteins increased. The expression of solute carrier family 7 genes, ChaC glutathione-specific gamma-glutamylcyclotransferase 1, and 5S ribosomal RNA gene was up-regulated the most in cells exposed to PFOA for 24 h, and the KEGG pathway analysis revealed that PFOA the most affected metabolic pathways and olfactory transduction. More importantly, PPAR alpha, fatty acid binding protein 1, and CYP450 family 1 subfamily A member 1 were identified as the target proteins for binding between PFOA and cells. Taken together, we suggest that disruption of mitochondrial integrity and function may contribute closely to PFOA-induced cell proliferation inhibition., 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 Ltd.)

Microbial transformation of per- and polyfluoroalkyl substances (PFAS), including fluorotelomer-derived PFAS, by native microbial communities in the environment has been widely documented. However, few studies have identified the key microorganisms and their roles during the PFAS biotransformation processes. This study was undertaken to gain more insight into the structure and function of soil microbial communities that are relevant to PFAS biotransformation. We collected 16S rRNA gene sequencing data from 8:2 fluorotelomer alcohol and 6:2 fluorotelomer sulfonate biotransformation studies conducted in soil microcosms under various redox conditions. Through co-occurrence network analysis, several genera, including Variovorax , Rhodococcus , and Cupriavidus , were found to likely play important roles in the biotransformation of fluorotelomers. Additionally, a metagenomic prediction approach (PICRUSt2) identified functional genes, including 6-oxocyclohex-1-ene-carbonyl-CoA hydrolase, cyclohexa-1,5-dienecarbonyl-CoA hydratase, and a fluoride-proton antiporter gene, that may be involved in defluorination. This study pioneers the application of these bioinformatics tools in the analysis of PFAS biotransformation-related sequencing data. Our findings serve as a foundational reference for investigating enzymatic mechanisms of microbial defluorination that may facilitate the development of efficient microbial consortia and/or pure microbial strains for PFAS biotransformation.

Per- and polyfluoroalkyl substances (PFAS) are a class of over 8000 chemicals, many of which are persistent, bioaccumulative, and toxic to humans, livestock, and wildlife. Serum protein binding affinity is instrumental in understanding PFAS toxicity, yet experimental binding data is limited to only a few PFAS congeners. Previously, we demonstrated the usefulness of a high-throughput, in vitro differential scanning fluorimetry assay for determination of relative binding affinities of human serum albumin for 24 PFAS congeners from 6 chemical classes. In the current study, we used this assay to comparatively examine differences in human, bovine, porcine, and rat serum albumin binding of 8 structurally informative PFAS congeners from 5 chemical classes. With the exception of the fluorotelomer alcohol 1H, 1H, 2H, 2H-perfluorooctanol (6:2 FTOH), each PFAS congener bound by human serum albumin was also bound by bovine, porcine, and rat serum albumin. The critical role of the charged functional headgroup in albumin binding was supported by the inability of albumin of each species tested to bind 6:2 FTOH. Significant interspecies differences in serum albumin binding affinities were identified for each of the bound PFAS congeners. Relative to human albumin, perfluoroalkyl carboxylic and sulfonic acids were bound with greater affinity by porcine and rat serum albumin, and the perfluoroalkyl ether acid congener bound with lower affinity to porcine and bovine serum albumin. These comparative affinity data for PFAS binding by serum albumin from human, experimental model, and livestock species reduce critical interspecies uncertainty and improve accuracy of predictive bioaccumulation and toxicity assessments for PFAS., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Perfluorooctanoic acid (PFOA) is an emerging persistent organic pollutant. Exposure to PFOA was observed to have a correlation with the expression levels of phospholipids. However, there are currently no studies that directly visualize the effects of PFOA on phospholipids. To this end, matrix-assisted laser desorption/ionization time of flight imaging mass spectrometry (MALDI-TOF-IMS) was used to visualize changes in phospholipids in the different tissues of zebrafish following exposure to PFOA. This study found that the major perturbed phospholipids were phosphatidylcholine (PC), diacylglycerol (DG), phosphatidic acid (PA), phosphatidylglycerol (PG), sphingomyelin (SM), and triacylglycerol (TG). These perturbed phospholipids caused by PFOA were reversible in some tissues (liver, gill, and brain) and irreversible in others (such as the highly exposed intestine). Moreover, the spatial distribution of perturbed phospholipids was mainly located around the edge or center of the tissues, implying that these tissue regions need special attention. This study provides novel insight into the biological toxicity and toxicity mechanisms induced by emerging environmental pollutants.

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.)

Known for their high stability and surfactant properties, per- and polyfluoroalkyl substances (PFAS) have been widely used in a range of manufactured products. Despite being largely phased out due to concerns regarding their persistence, bioaccumulation, and toxicity, legacy PFAS such as perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid continue to persist at high levels in the environment, posing risks to aquatic organisms. We used high-resolution magic angle spinning nuclear magnetic resonance spectroscopy in intact zebrafish (Danio rerio) embryos to investigate the metabolic pathways altered by PFOS both before and after hatching (i.e., 24 and 72 h post fertilization [hpf], respectively). Assessment of embryotoxicity found embryo lethality in the parts-per-million range with no significant difference in mortality between the 24- and 72-hpf exposure groups. Metabolic profiling revealed mostly consistent changes between the two exposure groups, with altered metabolites generally associated with oxidative stress, lipid metabolism, energy production, and mitochondrial function, as well as specific targeting of the liver and central nervous system as key systems. These metabolic changes were further supported by analyses of tissue-specific production of reactive oxygen species, as well as nontargeted mass spectrometric lipid profiling. Our findings suggest that PFOS-induced metabolic changes in zebrafish embryos may be mediated through previously described interactions with regulatory and transcription factors leading to disruption of mitochondrial function and energy metabolism. The present study proposes a systems-level model of PFOS toxicity in early life stages of zebrafish, and also identifies potential biomarkers of effect and exposure for improved environmental biomonitoring. Environ Toxicol Chem 2024;43:896-914. © 2024 SETAC., (© 2024 SETAC.)

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.)