PFAS-Biomolecule Interactions: Case Study Using Asclepios Nodes and Automated Workflows in KNIME for Drug Discovery and Toxicology.

The Asclepios suite of KNIME nodes represents an innovative solution for conducting cheminformatics and computational chemistry tasks, specifically tailored for applications in drug discovery and computational toxicology. This suite has been developed using open-source and publicly accessible software. In this chapter, we introduce and explore the Asclepios suite through the lens of a case study. This case study revolves around investigating the interactions between per- and polyfluorinated alkyl substances (PFAS) and biomolecules, such as nuclear receptors. The objective is to characterize the potential toxicity of PFAS and gain insights into their chemical mode of action at the molecular level. The Asclepios KNIME nodes have been designed as versatile tools capable of addressing a wide range of computational toxicology challenges. Furthermore, they can be adapted and customized to accomodate the specific needs of individual users, spanning various domains such as nanoinformatics, biomedical research, and other related applications. This chapter provides an in-depth examination of the technical underpinnings and foundations of these tools. It is accompanied by a practical case study that demonstrates the utilization of Asclepios nodes in a computational toxicology investigation. This showcases the extendable functionalities that can be applied in diverse computational chemistry contexts. By the end of this chapter, we aim for readers to have a comprehensive understanding of the effectiveness of the Asclepios node functions. These functions hold significant potential for enhancing a wide spectrum of cheminformatics applications.

Levels and trends of persistent organic pollutants in human populations living in the Arctic.

The Arctic Monitoring Assessment Program (AMAP) is tasked with monitoring and assessing the status of environmental contaminants in the Arctic, documenting levels and trends, and producing science-based assessments. The objectives of this paper are to present the current levels of persistent organic pollutants (POPs) across the Arctic, and to identify trends and knowledge gaps as detailed in the most recent AMAP Human Health Assessment Report. Many Arctic populations continue to have elevated levels of these contaminants, and the highest levels of POPs were observed in populations from Greenland, Faroe Islands, and Nunavik (Canada), as well as populations in the coastal Chukotka district (Russia) for legacy POPs only. Concentrations of most POPs are declining in Arctic populations in regions where time trends data exist, although the declines are not consistent across all regions. The exceptions are per- and polyfluoroalkyl substances, with concentrations of some long-chain PFAS such as perfluorononanoic acid increasing in populations in Nunavik, Greenland and Sweden. This paper provides a more extensive summary of levels of contaminants in adults, pregnant women, and children across the Arctic than previous AMAP human health assessments, particularly for levels of long-chain PFAS, which are currently under consideration for inclusion in the Stockholm Convention.

An in vitro and machine learning framework for quantifying serum albumin binding of per- and polyfluoroalkyl substances.

Per- and polyfluoroalkyl substances (PFAS) are a diverse class of anthropogenic chemicals; many are persistent, bioaccumulative, and mobile in the environment. Worldwide, PFAS bioaccumulation causes serious adverse health impacts, yet the physiochemical determinants of bioaccumulation and toxicity for most PFAS are not well understood, largely due to experimental data deficiencies. As most PFAS are proteinophilic, protein binding is a critical parameter for predicting PFAS bioaccumulation and toxicity. Among these proteins, human serum albumin (HSA) is the predominant blood transport protein for many PFAS. We previously demonstrated the utility of an in vitro differential scanning fluorimetry assay for determining relative HSA binding affinities for 24 PFAS. Here, we report HSA affinities for 65 structurally diverse PFAS from 20 chemical classes. We leverage these experimental data, and chemical/molecular descriptors of PFAS, to build 7 machine learning classifier algorithms and 9 regression algorithms, and evaluate their performance to identify the best predictive binding models. Evaluation of model accuracy revealed that the top performing classifier model, logistic regression, had an AUROC statistic of 0.936. The top performing regression model, support vector regression, had an R2 of 0.854. These top performing models were then used to predict HSA-PFAS binding for chemicals in the EPAPFASINV list of 430 PFAS. These developed in vitro and in silico methodologies represent a high-throughput framework for predicting protein-PFAS binding based on empirical data, and generate directly comparable binding data of potential use in predictive modeling of PFAS bioaccumulation and other toxicokinetic endpoints.

Spectral induced polarization (SIP) measurements across a PFAS-contaminated source zone.

There is a need to develop field-scale, in situ screening technologies for assessing variations in aqueous film-forming foam (AFFF) concentrations in soils at former fire training and storage sites. Field-scale Spectral Induced Polarization (SIP) geophysical measurements were acquired on a transect crossing an AFFF source zone. Soil samples were acquired to determine variations in poly- and per-fluoroalkyl substances (PFAS) concentrations in soils, characterize soil texture, and create triplicate soil columns for laboratory SIP measurements. Field and laboratory observations show that SIP measurements are sensitive to the concentration of AFFF constituents associated with soil pore surface area. The specific polarizability and the phase of the SIP measurements for the laboratory samples were linearly correlated with total soil-sorbed PFAS concentration. The phase from the field SIP measurements was highest over the location of maximum PFAS concentration measured on the laboratory samples. However, a significant correlation between field-measured phase and laboratory-measured total PFAS concentration still needs to be established. These observations, along with the demonstrated sensitivity of the SIP response to the removal of soil PFAS using a methanol wash procedure, support the case for SIP characterization of AFFF source zones.

Advances in perfluoro-alkylated compounds (PFAS) detection in seafood and marine environments: A comprehensive review on analytical techniques and global regulations.

Per- and poly-fluoroalkyl substances (PFAS) are persistent organic pollutants that severely threaten the environment and human health due to their distinct chemical composition, extensive production, widespread distribution, bioaccumulation in nature, and long-term persistence. This review focuses on the occurrence and sources of PFAS in seafood, with a particular emphasis on advanced detection methods viz. nanoparticle-based, biosensor-based, and metal-organic frameworks-based, and mass spectrometric techniques. The challenges associated with these advanced detection technologies are also discussed. Recent research and regulatory updates about PFAS, including hazardous and potential health effects, epidemiological studies, and various risk assessment models, have been reviewed. In addition, the need for global monitoring programs and regulations on PFAS are critically reviewed by underscoring their crucial role in protecting human health and the environment. Further, approaches for reducing PFAS in seafood are highlighted with future innovative remediation directions. Although advanced PFAS analytical methods are available, selectivity, sample preparation, and sensitivity are still significant challenges associated with detection of PFAS in seafood matrices.  Moreover, crucial research gaps and solutions to essential concerns are critically explored in this review.

Critical Evaluation and Meta-Analysis of Ecotoxicological Data on Per- and Polyfluoroalkyl Substances (PFAS) in Freshwater Species.

Despite the increasing concern regarding the ecological risks posed by per- and polyfluoroalkyl substances (PFAS), a lack of comprehensive understanding of their actual ecotoxicity remains. Through a meticulous examination of 91 peer-reviewed studies investigating effects at a population level and constructing probabilistic species sensitivity distributions (PSSDs), we present a state-of-the-science hazard assessment of PFAS in freshwater species. Using data subsets containing suboptimal data led to an overestimation of the predicted no-effect concentrations (PNECs) of PFAS. We report PNECs of perfluoroalkyl carboxylic acids (PFCAs) and perfluoroalkyl sulfonates (PFSAs) in freshwater to be 4.8-2000 µg/L and 0.4-8.9 µg/L, respectively, derived from high-quality data. Statistical analyses revealed that both functional groups and carbon chain length significantly influenced (p < 0.05) the variations in toxicity observed among different PFAS. This study underscores the importance of obtaining high-quality PFAS ecotoxicity data to comprehend associated hazards. The PNECs of PFAS derived in this study are higher compared to those of micro/nanoplastics and persistent organic pollutants. Our research offers valuable insights into prioritizing the regulation of more toxic PFAS.

Mobility and persistence of pesticides and emerging contaminants in age-dated and redox-classified groundwater under a range of land use types.

Understanding groundwater contamination patterns is hampered by the heterogeneous groundwater age and redox status over the depth range typically sampled for identifying pesticides and emerging contaminants threats. This study explores depth patterns of groundwater age and redox status across various land use types, unraveling spatial and temporal trends of pesticides and emerging contaminants using data from groundwater quality monitoring in the south of the Netherlands. The Netherlands is an ideal testing ground due to its high population density and widespread groundwater contamination from multiple sources. 146 multi-level observation wells were age-dated using 3H/3He, and contaminant concentrations were analyzed based on recharge year, land use type, and redox conditions, mitigating uncertainties from spatial and depth-dependent variations in both groundwater age and redox status. Redox-recharge year diagrams were developed to visually evaluate contaminant patterns in relation to these factors and to assess concentration patterns in relation to contamination history. Most detections of pesticides, metabolites, and emerging contaminants occurred in the youngest recharge periods (2000-2010 and 2010-2020) and in agricultural areas. However, certain contaminants, including BAM, desphenyl-chloridazon, short-chain PFCAs, PFOA, and EDTA, were consistently found in older water and Fe- or SO4-reduced conditions, indicating their mobility and persistence in the regional groundwater system. Comparing the presence of contaminants in specific redox classes and recharge periods with known application or leaching history provides insights into retardation (e.g., PFOS) and degradation (e.g., 2-hydroxy-atrazine, benzotriazole), explaining lower detection frequencies in earlier recharge periods. Identifying recharge years from age-dated groundwater helps relate contaminants to farmland application or river water recharge periods, revealing leaching history and contamination origins. The presented framework has the potential to enhance the interpretation of large groundwater datasets from dedicated, short-screened observation wells, such as those from the Danish GRUMO network, the Dutch monitoring networks, and parts of the US National Water Quality Program.

Insights into the neurotoxicity and oxidative stress to the freshwater amphipod Hyalella azteca induced by hexafluoropropylene oxide trimer acid.

With the regulation and phase-out of conventional per- and polyfluoroalkyl substances (PFAS), there is a growing trend towards seeking alternatives that are less toxic and less persistent. Hexafluoropropylene oxide trimer acid (HFPO-TA) is one of the alternatives to perfluorooctanoic acid (PFOA), the latter being widely present in the environment globally. However, there is limited information regarding the biological toxicity of HFPO-TA to aquatic organisms. In this study, the freshwater benthic amphipod, Hyalella azteca, was used to assess the acute and chronic toxicity of HFPO-TA in both water and sediment. HFPO-TA was found to be more toxic to H. azteca than PFOA, as indicated by greater production of reactive oxygen species (p < 0.05) and increasing catalase activity (p < 0.05). In addition, exposure to HFPO-TA affected the swimming behavior and the acetylcholinesterase (AChE) activity of the amphipod. Molecular docking models revealed that HFPO-TA can bind to AChE with a stronger binding affinity than PFOA. Furthermore, an integrated biomarker response index indicated that environmentally relevant concentration (1-100 µg/L) of HFPO-TA may cause toxicity to H. azteca, encompassing oxidative stress and neurotoxicity. This study provides new insights into the toxicity mechanisms of HFPO-TA and is valuable for assessing the ecological safety of this compound.

Atmospheric concentrations of per- and polyfluoroalkyl substances and their emissions at a waste recycling facility producing refuse-derived paper and plastics densified fuel.

To better understand the types and concentrations of per- and polyfluoroalkyl substances (PFAS) emitted into the air from waste recycling facilities that produce refuse-derived paper and plastics densified fuel (RPF) from industrial waste, we conducted an air sampling campaign at a waste recycling facility in Japan. Both passive and active air sampling were conducted, and the samples collected were used to quantify the PFAS emitted into the air during the production of RPF. Overall, few ionic PFAS were detected in the air at the facility; however, high levels of neutral PFAS (8.21-53.4 ng/m3; 20.7-130 pmol/m3) were measured in the air near the heat molding machines. The two neutral PFAS detected at the highest concentrations were 6:2 fluorotelomer alcohol and 6:2 fluorotelomer methacrylate, which are currently unregulated under the Stockholm Convention, suggesting that product manufacturers have shifted away from using regulated PFAS. Small amounts of regulated PFAS such as 8:2 fluorotelomer methacrylate and 8:2 fluorotelomer acrylate were measured in some parts of the facility. Analysis of the concentrations of PFAS in the exhaust gas from the heat molding machines revealed neutral PFAS concentrations (537-2160 ng/m3; 1350-5040 pmol/m3) that were 1-2 orders of magnitude higher than those in the surrounding indoor air. The total emission of neutral PFAS from the facility to the environment was estimated to be 0.066-0.260 g/day (0.168-0.607 mmol/day), depending on whether air volume discharged as exhaust gas or as indoor ventilation was considered. A contribution analysis of the emissions revealed that treating the exhaust gas from the heat molding machines, which constitutes over 94 % of the total emissions, is very effective at reducing PFAS emissions from the facility.

Causative mechanisms limiting the removal efficiency of short-chain perfluoroalkyl substances by activated carbon.

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

Assessing the Effects of Fluorine-Free and PFAS-Containing Firefighting Foams on Development and Behavioral Responses Using a Zebrafish-Based Platform.

Significant progress has been made in developing fluorine-free firefighting foams (F3) as alternatives to perfluoroalkyl substances (PFAS)-containing aqueous film-forming foams (AFFF) to help eliminate the health and environmental concerns linked to PFAS exposure. However, developing viable F3 options hinges on a thorough assessment of potential risks alongside technical performance evaluations. This study showcases the capability of a zebrafish-based platform to discern the developmental and behavioral toxicities associated with exposure to one AFFF and two F3 formulations. To facilitate direct exposure to the chemicals, embryos were enzymatically dechorionated and then exposed to the diluted formulations (6 - 120 hours post fertilization (hpf)) at concentrations folding from 0.1% of the manufacturer-recommended working concentrations. The exposure regimen also included daily automated media changes (50%) and mortality assessments (24 and 120 hpf). At 120 hpf, a comprehensive assessment encompassing overall development, prevalence of morphological defects, and behavioral responses to acute stressors (visual, acoustic, and peripheral irritant) was conducted. Exposure to both F3s significantly increased larval mortalities to percentages exceeding 90%, whereas AFFF exposures did not cause any significant effect. Overall development, marked by total larval length, was significantly impacted following exposures to all foams. Behavioral responses to acute stressors were also significantly altered following exposures to both F3s, whereas the AFFF did not alter behavior at the concentrations tested. Our findings demonstrate toxicities associated with tested F3 formulations that encompass several endpoints and highlight the utility of the proposed platform in evaluating the developmental toxicities of current and future foam formulations.

Cross-cutting studies of per- and polyfluorinated alkyl substances (PFAS) in Arctic wildlife and humans.

This cross-cutting review focuses on the presence and impacts of per- and polyfluoroalkyl substances (PFAS) in the Arctic. Several PFAS undergo long-range transport via atmospheric (volatile polyfluorinated compounds) and oceanic pathways (perfluorinated alkyl acids, PFAAs), causing widespread contamination of the Arctic. Beyond targeting a few well-known PFAS, applying sum parameters, suspect and non-targeted screening are promising approaches to elucidate predominant sources, transport, and pathways of PFAS in the Arctic environment, wildlife, and humans, and establish their time-trends. Across species, concentrations were dominated by perfluorooctanesulfonic acid (PFOS), followed by perfluorononanoic acid (PFNA); highest concentrations were present in mammalian livers and bird eggs. Time trends were similar for East Greenland ringed seals (Pusa hispida) and polar bears (Ursus maritimus). In polar bears, PFOS concentrations increased from the 1980s to 2006, with a secondary peak in 2014-2021, while PFNA increased regularly in the Canadian and Greenlandic ringed seals and polar bear livers. Human time trends vary regionally (though lacking for the Russian Arctic), and to the extent local Arctic human populations rely on traditional wildlife diets, such as marine mammals. Arctic human cohort studies implied that several PFAAs are immunotoxic, carcinogenic or contribute to carcinogenicity, and affect the reproductive, endocrine and cardiometabolic systems. Physiological, endocrine, and reproductive effects linked to PFAS exposure were largely similar among humans, polar bears, and Arctic seabirds. For most polar bear subpopulations across the Arctic, modeled serum concentrations exceeded PFOS levels in human populations, several of which already exceeded the established immunotoxic thresholds for the most severe risk category. Data is typically limited to the western Arctic region and populations. Monitoring of legacy and novel PFAS across the entire Arctic region, combined with proactive community engagement and international restrictions on PFAS production remain critical to mitigate PFAS exposure and its health impacts in the Arctic.

Forecasting and Hindcasting PFAS Concentrations in Groundwater Discharging to Streams near a PFAS Production Facility.

Per- and polyfluoroalkyl substances (PFAS) are known to be highly persistent in groundwater, making it vital to develop new approaches to important practical questions such as the time scale for future persistence of PFAS in contaminated groundwater. In the approach presented here, groundwater from beneath streambeds was analyzed for PFAS and age-dated using SF6 and 3H/3He. The results were coupled with groundwater flux measurements in a convolution approach to estimate past and future PFAS concentrations in groundwater discharge to the streams. At our test site near the Cape Fear River (CFR) of North Carolina, PFAS were detected in groundwater up to 43 years old, suggesting that some PFAS entered groundwater immediately or shortly after fluorochemical production began at the nearby Fayetteville Works. Results are consistent with little to no retardation in groundwater for perfluoroethers such as hexafluoropropylene oxide-dimer acid (HFPO-DA) and perfluoro-2-methoxypropanoic acid (PMPA), the two most abundant PFAS, with mean concentrations of 229 and 498 ng/L, respectively. Future PFAS concentrations in groundwater discharge to streams were estimated to remain above current MCL or health advisory levels through at least 2050 or 2060 (using 3H/3He and SF6, respectively). Recent atmospheric deposition data suggest lower but non-negligible amounts of PFAS may continue to enter groundwater, likely further extending PFAS persistence in groundwater and the adjacent CFR. This approach shows promise for giving an overall perspective on persistence of PFAS in groundwater discharge from a broad contaminated area.

Per- and polyfluoroalkyl substances behavior: Insights from autothermal thermophilic aerobic digestion - Storage nitrification-denitrification reactors.

Per- and polyfluoroalkyl substances (PFAS) have emerged as significant environmental contaminants due to their persistence, bioaccumulative properties, and potential adverse impacts on health and ecosystems. Water Resource Recovery Facilities (WRRFs) play a crucial role in the management of PFAS, given their widespread presence in consumer products and subsequent reintroduction into the environment. This study investigated the dynamics of PFAS within the solids stream treatment processing that utilized autothermal thermophilic aerobic digestion (ATAD) followed by a storage nitrification-denitrification reactor (SNDR). PFAS analysis included 60 PFAS analyzed via liquid chromatography-triple quadrupole time-of-flight mass spectrometry of pre-ATAD, post-ATAD, and post-SNDR samples. Complexities such as volatile solids loss during the treatment processes were considered in assessing the effect of ATAD and SNDR on PFAS concentrations. Significant changes were observed in the relative contributions of various PFAS classes throughout the treatment processes due to biotransformation; similar changes were reflected in both 2019 and 2021. The relative contribution of perfluoroalkyl alkyl acids (PFAAs) increased while phosphorus-containing PFAS (e.g., di-substituted polyfluoroalkyl phosphate esters) and fluorotelomer carboxylic acids decreased. Shorter-chain PFAAs were enriched during ATAD, whereas most PFAS increased during SNDR except diPAPs and FTCAs, reflecting treatment conditions' impact. Overall, minor decreases in total PFAS concentrations during ATAD as well as SNDR were observed and hypothesized to be due to enhanced biotransformation to ultra-short PFAS that were not quantified. Even with up to 60 PFAS quantified in the samples, PFAS accounted for <1% of the total fluorine with <2% of that total fluorine being fluoride prompting interest in additional exploration.

Per- and polyfluoroalkyl substances contamination of drinking water sources in Africa: Pollution sources and possible treatment methods.

Despite the detection of poly- and perfluorinated alkyl substances (PFAS) in the water system in Africa, the effort towards mitigating PFAS in water in Africa needs to be better understood. Therefore, this review evaluated the contamination status and mitigation methods for handling PFAS-contaminated water systems in Africa. The findings revealed the presence of PFAS in wastewater treatment plant (WWTP) effluents, surface water and commercially available bottled and tap water in African countries. The concentration of PFAS in drinking water sources reviewed ranged from < limits of quantification to 778 ng L-1. The sources of PFAS in water systems in Africa are linked to uncontrolled importation of PFAS-containing products, WWTP effluents and inappropriate disposal of PFAS-containing materials. The information on treatment methods for PFAS-contaminated water systems is scanty. Unfortunately, the treatment method is challenged by poor water research infrastructure and facilities, lack of awareness, poor research funding and weak legislation; however, adsorption and membrane technology seem favourable for removing PFAS from water systems in Africa. It is essential to focus on monitoring and assessing drinking water quality in Africa to reduce the disease burden that this may cause. Most African countries' currently implemented water treatment facilities cannot efficiently remove PFAS during treatment. Therefore, governments in Africa need to fund more research to develop an efficient water treatment technique that is sustainable in Africa.

Contamination levels of per- and polyfluoroalkyl substances (PFAS) in recent North American precipitation events. A review.

Per- and polyfluoroalkyl substances (PFAS), known as forever chemicals, have received international attention over the last two decades for their health risks and environmental persistence. One pathway of human exposure to PFAS is by rainwater. This review aims to analyze current studies of legacy and emerging PFAS contamination levels in rainwater in North America. In April 2024, the US Environmental Protection Agency (EPA) finalized new regulations for PFAS levels in drinking water. This review compares PFAS in rainwater to the latest US EPA regulation for the first time. Our analysis determined that five recent studies' average total PFAS (ΣPFAS) ranged from 2.28 to 92.42 ng/L and had a hazard index (HI) of 0.05-0.30. The average ΣPFAS and HI for all five studies are below the maximum contamination levels (MCLs) recommended by the EPA. However, rainwater samples collected near local point sources often exceeded the MCLs. To better understand the extent of PFAS contamination in the United States, more studies need to be conducted and analyzed throughout North America, testing for both legacy and emerging PFAS and locating local point sources.

Exploring maternal and developmental toxicity of perfluoroalkyl ether acids PFO4DA and PFO5DoA using hepatic transcriptomics and serum metabolomics.

Production of per- and polyfluoroalkyl substances (PFAS) has shifted from long-chain perfluoroalkyl acids to short-chain compounds and those with ether bonds in the carbon chain. Next-generation perfluoroalkylether PFAS include HFPO-DA ("GenX chemicals"), Nafion Byproducts, and the PFOx homologous series that includes perfluoro-3,5,7,9-butaoxadecanoic acid (PFO4DA) and perfluoro-3,5,7,9,11-pentaoxadodecanoic acid (PFO5DoA). PFO4DA and PFO5DoA have been detected in serum and/or tissues from humans and wildlife proximal to contamination point sources. However, toxicity data are extremely limited, with no in vivo developmental toxicology data. To address these data gaps, pregnant Sprague-Dawley rats were exposed via oral gavage to vehicle, PFO4DA, or PFO5DoA across a series of doses (0.1 to 62.5 mg/kg/day) from gestation day (GD) 18-22. Hepatic transcriptomics were assayed in dams and fetuses, and serum metabolomics in dams. These data were overlaid with serum PFO4DA and PFO5DoA concentrations to perform dose-response modeling. Both dams and fetuses exhibited dose-responsive disruption of hepatic gene expression in response to PFO4DA or PFO5DoA, with fetal expression disrupted at lower doses than dams. Several differentially expressed genes were upregulated by every dose of PFO5DoA in both maternal and fetal samples, including genes encoding enzymes that hydrolyze acyl-coA to free fatty acids. Maternal serum metabolomics revealed PFO4DA exposure did not induce significant changes at any tested dose, whereas PFO5DoA exposure resulted in dose-dependent differential metabolite abundance for 149 unique metabolites. Multi-omics pathway analyses of integrated maternal liver transcriptomics and serum metabolomics revealed significant convergent changes as low as 3 mg/kg/d PFO4DA and 0.3 mg/kg/d PFO5DoA exposure. Overall, transcriptomic and metabolomic effects of PFO4DA and PFO5DoA appear consistent with other carboxylic acid PFAS, with primary changes related to lipid metabolism, bile acids, cholesterol, and cellular stress. Importantly, PFO5DoA exposure more potently induced changes in maternal and fetal hepatic gene expression and maternal circulating metabolites, despite high structural similarity. Further, we report in vitro PPARα and PPARγ receptor activation for both compounds as putative molecular mechanisms. This work demonstrates the potential developmental toxicity of alternative moiety perfluoroethers and highlights the developing liver as particularly vulnerable to transcriptomic disruption. Synopsis: Developmental exposure to fluoroether carboxylic acids PFO4DA and PFO5DoA result in differential impacts on hepatic transcriptome in dams and offspring and circulating metabolome in dams, with PFO5DoA exhibiting higher potency than PFO4DA.

Per- and polyfluoroalkyl substances (PFAS) in drinking water in Southeast Los Angeles: Industrial legacy and environmental justice.

Per- and polyfluoroalkyl substances (PFAS) are persistent chemicals of increasing concern to human health. PFAS contamination in water systems has been linked to a variety of sources including hydrocarbon fire suppression activities, industrial and military land uses, agricultural applications of biosolids, and consumer products. To assess PFAS in California tap water, we collected 60 water samples from inside homes in four different geographic regions, both urban and rural. We selected mostly small water systems with known history of industrial chemical or pesticide contamination and that served socioeconomically disadvantaged communities. Thirty percent of the tap water samples (18) had a detection of at least one of the 32 targeted PFAS and most detections (89 %) occurred in heavily industrialized Southeast Los Angeles (SELA). The residents of SELA are predominately Latino and low-income. Concentrations of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) ranged from 6.8 to 13.6 ng/L and 9.4-17.8 ng/L, respectively in SELA and were higher than State (PFOA: 0.007 ng/L; PFOS: 1.0 ng/L) and national health-based goals (zero). To look for geographic patterns, we mapped potential sources of PFAS contamination, such as chrome plating facilities, airports, landfills, and refineries, located near the SELA water systems; consistent with the multiple potential sources in the area, no clear spatial associations were observed. The results indicate the importance of systematic testing of PFAS in tap water, continued development of PFAS regulatory standards and advisories for a greater number of compounds, improved drinking-water treatments to mitigate potential health threats to communities, especially in socioeconomically disadvantaged and industrialized areas.

Can pyrolysis and composting of sewage sludge reduce the release of traditional and emerging pollutants in agricultural soils? Insights from field and laboratory investigations.

The potential extractability, crop uptake, and ecotoxicity of conventional and emerging organic and metal(loid) contaminants after the application of pre-treated (composted and pyrolysed) sewage sludges to two agricultural soils were evaluated at field and laboratory scale. Metal(loid) extractability varied with sludge types and pre-treatments, though As, Cu, and Ni decreased universally. In the field, the equivalent of 5 tons per hectare of both composted and pyrolysed sludges brought winter wheat grain metal(loid) concentrations below statutory limits. Carbamazepine, diclofenac, and telmisartan were the only detected organic pollutants in crops decreasing in order of root > shoot > grains, whilst endocrine-disrupting chemicals, such as bisphenol A and perfluorochemicals were heavily reduced by composting (up to 71%) or pyrolysis (up to below detection limit) compared to raw sludges. As a consequence, no detectable concentrations were measured in soils 12 months after field application. This study highlights the potential advantages of processing sewage sludge before soil applications, especially in the context of reducing the mobility of emerging contaminants, though further studies are required on a broad range of soils and crops before land application can be considered.

Molecular designing of potential environmentally friendly PFAS based on deep learning and generative models.

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are widely used across a spectrum of industrial and consumer goods. Nonetheless, their persistent nature and tendency to accumulate in biological systems pose substantial environmental and health threats. Consequently, striking a balance between maximizing product efficiency and minimizing environmental and health risks by tailoring the molecular structure of PFAS has become a pivotal challenge in the fields of environmental chemistry and sustainable development. To address this issue, a computational workflow was proposed for designing an environmentally friendly PFAS by incorporating deep learning (DL) and molecular generative models. The hybrid DL architecture MolHGT+ based on heterogeneous graph neural network with transformer-like attention was applied to predict the surface tension, bioaccumulation, and hepatotoxicity of the molecules. Through virtual screening of the PFAS master database using MolHGT+, the findings indicate that incorporating the siloxane group and betaine fragment can effectively decrease both the bioaccumulation and hepatotoxicity of PFAS while preserving low surface tension. In addition, molecular generative models were employed to create a structurally diverse pool of novel PFASs with the aforementioned hit molecules serving as the initial template structures. Overall, our study presents a promising AI-driven method for advancing the development of environmentally friendly PFAS.