Journal articles: 'PFAS toxicity'

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Seo, Sung-Hee. "Health risk of Human Exposure to Perfluorinated Compounds (PFASs) in Hyeongsan River, Pohang." Journal of Environmental Analysis, Health and Toxicology 25, no. 3 (September 30, 2022): 77–84. http://dx.doi.org/10.36278/jeaht.25.3.77.

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The aim of this study was to assess human health risks of exposure to perfluoroalkyl substances (PFASs) by ingestion of water from the Hyeongsan River in Pohang. Ingestion primarily acquired PFBS, PFNA, PFOS, and PFOA, but PFAAs rather than its precursors. Human exposure to PFASs was affected by the physicochemical properties of compounds, the emission sources, and the flow rate. The upstream and midstream waters were influenced by PFCAs due to the domestic sewage, whereas the downstream water contained high levels of PFBS and PFOS due to the presence of an industrial complex. Exposure levels decreased in the midstream; this result suggests a dilution effect due to the increasing flow rate. Exposure levels to PFBS were high exposure because they have a low octanol–water partition coefficient and high aqueous solubility. PFOS at the industrial complex exceeded the WHO allowable level; this result suggests that ingestion may cause non-carcinogenic toxicity. To our knowledge, this is the first assessment of the risk of PFAS ingestion in Pohang. The result will provide a useful reference for future regulations and policies to manage PFAS sources, purify river water, and prevent human exposure.

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Seo, Sung-Hee. "Risk Assessment of Inhalation Exposure to Per-and Polyfluoroalkyl Substances (PFASs) in Industrial, Urban-residential and Rural Areas Near Hyeongsan River, Pohang." Journal of Environmental Analysis, Health and Toxicology 25, no. 2 (June 30, 2022): 51–57. http://dx.doi.org/10.36278/jeaht.25.2.51.

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The goal of this study was to evaluate human exposure to per- and polyfluoroalkyl substances (PFASs) in the air near the Hyeongsan River in Pohang, and to quantify associated health risks. The daily intake of PFOS was the highest, and those of PFBS, PFHxA, PFUnDA, and PFOA were also high. Humans were exposed more to ionic PFASs than to neutral PFASs. The exposure level of PFASs increased from upstream to downstream; this trend suggests that emission sources exist downstream. For the gaseous phase, the exposure level was highest to PFBS, which have the shortest carbon-chain length, whereas for the particulate phase, exposure was highest to PFOS. The exposure and distribution of PFAS congeners differed among sites and phases, which means that humans are exposed differently depending on the PFASs emitted from the emission source at each site, and on the physicochemical properties of PFASs. Inhalation exposure to PFASs was below the PFAS intake safety threshold, and the toxicity was also lower than the level allowed by WHO. However, health risks from long-term exposure to PFASs are of concern, and combining exposure by various routes may have a significant health effect. Therefore, continuous monitoring and risk assessment are required.

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Rowan-Carroll, Andrea, Anthony Reardon, Karen Leingartner, Remi Gagné, Andrew Williams, Matthew J. Meier, Byron Kuo, et al. "High-Throughput Transcriptomic Analysis of Human Primary Hepatocyte Spheroids Exposed to Per- and Polyfluoroalkyl Substances as a Platform for Relative Potency Characterization." Toxicological Sciences 181, no. 2 (March 27, 2021): 199–214. http://dx.doi.org/10.1093/toxsci/kfab039.

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Abstract Per- and poly-fluoroalkyl substances (PFAS) are widely found in the environment because of their extensive use and persistence. Although several PFAS are well studied, most lack toxicity data to inform human health hazard and risk assessment. This study focused on 4 model PFAS: perfluorooctanoic acid (PFOA; 8 carbon), perfluorobutane sulfonate (PFBS; 4 carbon), perfluorooctane sulfonate (PFOS; 8 carbon), and perfluorodecane sulfonate (PFDS; 10 carbon). Human primary liver cell spheroids (pooled from 10 donors) were exposed to 10 concentrations of each PFAS and analyzed at 4 time points. The approach aimed to: (1) identify gene expression changes mediated by the PFAS, (2) identify similarities in biological responses, (3) compare PFAS potency through benchmark concentration analysis, and (4) derive bioactivity exposure ratios (ratio of the concentration at which biological responses occur, relative to daily human exposure). All PFAS induced transcriptional changes in cholesterol biosynthesis and lipid metabolism pathways, and predicted PPARα activation. PFOS exhibited the most transcriptional activity and had a highly similar gene expression profile to PFDS. PFBS induced the least transcriptional changes and the highest benchmark concentration (ie, was the least potent). The data indicate that these PFAS may have common molecular targets and toxicities, but that PFOS and PFDS are the most similar. The transcriptomic bioactivity exposure ratios derived here for PFOA and PFOS were comparable to those derived using rodent apical endpoints in risk assessments. These data provide a baseline level of toxicity for comparison with other known PFAS using this testing strategy.

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Fey, Megan E., Philip E. Goodrum, N. Roxanna Razavi, Christopher M. Whipps, Sujan Fernando, and Janet K. Anderson. "Is Mixtures’ Additivity Supported by Empirical Data? A Case Study of Developmental Toxicity of PFOS and 6:2 FTS in Wildtype Zebrafish Embryos." Toxics 10, no. 8 (July 25, 2022): 418. http://dx.doi.org/10.3390/toxics10080418.

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Per- and polyfluoroalkyl substances (PFASs) are a major priority for many federal and state regulatory agencies charged with monitoring levels of emerging contaminants in environmental media and setting health-protective benchmarks to guide risk assessments. While screening levels and toxicity reference values have been developed for numerous individual PFAS compounds, there remain important data gaps regarding the mode of action for toxicity of PFAS mixtures. The present study aims to contribute whole-mixture toxicity data and advance the methods for evaluating mixtures of two key components of aqueous film-forming foams: perfluorooctanesulfonic acid (PFOS), and 6:2 fluorotelomer sulfonic acid (6:2 FTS). Wildtype (AB) zebrafish embryos were exposed to PFOS and 6:2 FTS, both as individual components and as binary mixtures, from 2 to 122 h post-fertilization. Five treatment levels were selected to encompass environmentally relevant exposure levels. Experimental endpoints consisted of mortality, hatching, and developmental endpoints, including swim bladder inflation, yolk sac area, and larval body length. Results from dose–response analysis indicate that the assumption of additivity using conventional points of departure (e.g., NOAEL, LOAEL) is not supported for critical effect endpoints with these PFAS mixtures, and that the interactions vary as a function of the dose range. Alternative methods for quantifying relative potency are proposed, and recommendations for additional investigations are provided to further advance assessments of the toxicity of PFAS mixtures to aquatic organisms.

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Ma, Tingting, Chaoran Ye, Tiantian Wang, Xiuhua Li, and Yongming Luo. "Toxicity of Per- and Polyfluoroalkyl Substances to Aquatic Invertebrates, Planktons, and Microorganisms." International Journal of Environmental Research and Public Health 19, no. 24 (December 13, 2022): 16729. http://dx.doi.org/10.3390/ijerph192416729.

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Per- and polyfluoroalkyl substances (PFASs), recognized worldwide as emerging pollutants, may pose a substantial threat to human health and our environment due to their stability, high concentrations, wide distribution, and easy accumulation. Ever since perfluorooctane sulfonate and perfluorooctanoic acid were recognized by the Stockholm Convention on Persistent Organic Pollutants, the public has become increasingly concerned about potential contamination and the environmental risks associated with PFASs. Ubiquitous PFAS contamination of drinking water, groundwater, surface water, and sediment has been detected, especially in areas with rapid industrial and economic development. Its accumulation in living organisms and foods has accentuated the importance of investigations into aquatic organisms at the bottom of the food chain, as the stability and integrity of the food web as well as the population quantity and structure of the aquatic ecosystem may be affected. This review provides a comprehensive summary of the toxic and toxicity-related effects of PFASs on aquatic plankton, aquatic invertebrates and microorganisms, the characteristics of different target aquatic organisms in toxicity investigations, and a feasibility evaluation of PFAS substitutes to provide valuable suggestions for further utilization and regulation of PFASs and their substitutes.

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Renfrew, Daniel, and Thomas W. Pearson. "The Social Life of the “Forever Chemical”." Environment and Society 12, no. 1 (September 1, 2021): 146–63. http://dx.doi.org/10.3167/ares.2021.120109.

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This article examines the social life of PFAS contamination (a class of several thousand synthetic per- and polyfluoroalkyl substances) and maps the growing research in the social sciences on the unique conundrums and complex travels of the “forever chemical.” We explore social, political, and cultural dimensions of PFAS toxicity, especially how PFAS move from unseen sites into individual bodies and into the public eye in late industrial contexts; how toxicity is comprehended, experienced, and imagined; the factors shaping regulatory action and ignorance; and how PFAS have been the subject of competing forms of knowledge production. Lastly, we highlight how people mobilize collectively, or become demobilized, in response to PFAS pollution/ toxicity. We argue that PFAS exposure experiences, perceptions, and responses move dynamically through a “toxicity continuum” spanning invisibility, suffering, resignation, and refusal. We off er the concept of the “toxic event” as a way to make sense of the contexts and conditions by which otherwise invisible pollution/toxicity turns into public, mass-mediated, and political episodes. We ground our review in our ongoing multisited ethnographic research on the PFAS exposure experience.

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Grandjean, P. "Epidemiological approaches to PFAS toxicity." Toxicology Letters 350 (September 2021): S53. http://dx.doi.org/10.1016/s0378-4274(21)00377-5.

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Parolini, Marco, Beatrice De Felice, Marianna Rusconi, Michelangelo Morganti, Stefano Polesello, and Sara Valsecchi. "A review of the bioaccumulation and adverse effects of PFAS in free-living organisms from contaminated sites nearby fluorochemical production plants." Water Emerging Contaminants & Nanoplastics 1, no. 4 (2022): 18. http://dx.doi.org/10.20517/wecn.2022.15.

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Per- and polyfluoroalkyl substances (PFAS) encompass a large, heterogeneous group of chemicals of potential concern to human and environmental health. Based on information for some legacy PFAS, such as perfluorooctane sulfonate and perfluorooctanoate, there is an increasing awareness that they can represent a serious environmental risk. Although the environmental occurrence and fate of some legacy PFAS and their toxicity under controlled laboratory conditions have been investigated, to date, there is a dearth of information on the exposure and potential adverse effects of these compounds towards free-living organisms. The present review summarizes the findings of field studies investigating the accumulation and adverse effects induced by the exposure to environmental mixtures of both legacy and emerging PFAS in the wildlife living nearby fluorochemical production plants (FCP). Biomonitoring campaigns performed close to FCP, which can be considered as hotspots of PFAS contamination, can be very useful in exploring the fate and toxicity of these compounds towards free-living organisms. All studies showed that the bioaccumulation of both legacy and emerging PFAS in wildlife living near the FCP is higher compared to control sites and other areas worldwide. However, the investigation on adverse effects returned contrasting results, suggesting the need for further studies to shed light on the toxicity and mechanism(s) of action of PFAS in free-living organisms.

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Umar, Muhammad. "Reductive and Oxidative UV Degradation of PFAS—Status, Needs and Future Perspectives." Water 13, no. 22 (November 11, 2021): 3185. http://dx.doi.org/10.3390/w13223185.

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Perfluoroalkyl and polyfluoroalkyl substances (PFASs) consist of a group of environmentally persistent, toxic and bio-accumulative organic compounds of industrial origin that are widely present in water and wastewater. Despite restricted use due to current regulations on their use, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) remain the most commonly detected long-chain PFAS. This article reviews UV-based oxidative and reductive studies for the degradation of PFAS. Most of the UV-based processes studied at lab-scale include low pressure mercury lamps (emitting at 254 and 185 nm) with some studies using medium pressure mercury lamps (200–400 nm). A critical evaluation of the findings is made considering the degradation of PFAS, the impact of water quality conditions (pH, background ions, organics), types of oxidizing/reducing species, and source of irradiation with emphasis given to mechanisms of degradation and reaction by-products. Research gaps related to understanding of the factors influencing oxidative and reductive defluorination, impact of co-existing ions from the perspective of complexation with PFAS, and post-treatment toxicity are highlighted. The review also provides an overview of future perspectives regarding the challenges in relation to the current knowledge gaps, and future needs.

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Emerce, Esra, and Özge Çetin. "Genotoxicity assessment of perfluoroalkyl substances on human sperm." Toxicology and Industrial Health 34, no. 12 (October 16, 2018): 884–90. http://dx.doi.org/10.1177/0748233718799191.

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Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are synthetic chemicals that have been used in industry and consumer products. Because the presence of PFAS has been identified in humans and the environment in the last decade, human exposure to PFAS is a current public health concern. It has been shown that some PFAS lead to adverse health effects in the male reproductive system. However, there is no information about probable genotoxic effects of these chemicals on sperm cells. This study aimed to investigate the possible genotoxic damage on human sperm cells exposed to certain major PFAS compounds that were selected considering their extensive usage, high persistence in the environment, and high bioaccumulation in humans. These PFAS are perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorohexanoic acid (PFHxA). The alkaline comet assay was used to detect the DNA damage to sperm. Sperm cells were treated with 0.1–1 mM of each PFAS at 32°C for 1 h to obtain optimal survival. As a result of the experiments, it was discovered that the exposure to PFOS, PFOA, PFNA, and PFHxA did not cause significant levels of cytotoxicity and did not cause damage to sperm DNA under these conditions. The results suggest that the exposure to these PFAS did not interfere with sperm DNA. Indirect toxicity mechanisms should be taken into account to assess the association between the PFAS exposure and male reproductive toxicity.

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Palazzolo, Stefano, Isabella Caligiuri, Andrea Augusto Sfriso, Matteo Mauceri, Rossella Rotondo, Davide Campagnol, Vincenzo Canzonieri, and Flavio Rizzolio. "Early Warnings by Liver Organoids on Short- and Long-Chain PFAS Toxicity." Toxics 10, no. 2 (February 18, 2022): 91. http://dx.doi.org/10.3390/toxics10020091.

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Short-chain per-fluoroalkyl substances (PFAS) have replaced long-chains in many applications, however the toxicity and its mode of action and interactions due to the large number of these compounds and their mixtures is still poorly understood. The paper aims to compare the effects on mouse liver organoids (target organ for bioaccumulation) of two long-chain PFAS (perfluorooctane sulfonate -PFOS-, perfluorooctanoic acid -PFOA) and two short-chain PFAS commonly utilized in the industry (heptafluorobutyric acid -HFBA-, Pentafluoropropionic anhydride-PFPA) to identify the mode of action of these classes of contaminants. Cytomorphological aberrations and ALT/GDH enzyme disruption were identified but no acute toxicity endpoint neither apoptosis was detected by the two tested short-chain PFAS. After cytomorphological analysis, it is evident that short-chain PFAS affected organoid morphology inducing a reduction of cytostructural complexity and aberrant cytological features. Conversely, EC50 values of 670 ± 30 µM and 895 ± 7 µM were measured for PFOS and PFOA, respectively, together with strong ALT/GDH enzyme disruption, caspase 3 and 7 apoptosis activation and deep loss of architectural complexity of organoids in the range of 500–1000 µM. Eventually, biochemical markers and histology analysis confirmed the sensitivity of organoid tests that could be used as a fast and reproducible platform to test many PFAS and mixtures saving time and at low cost in comparison with in vivo tests. Organoids testing could be introduced as an innovative platform to assess the toxicity to fast recognize potentially dangerous pollutants.

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Foguth, Rachel, Maria S. Sepúlveda, and Jason Cannon. "Per- and Polyfluoroalkyl Substances (PFAS) Neurotoxicity in Sentinel and Non-Traditional Laboratory Model Systems: Potential Utility in Predicting Adverse Outcomes in Human Health." Toxics 8, no. 2 (June 15, 2020): 42. http://dx.doi.org/10.3390/toxics8020042.

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Per- and polyfluoroalkyl substances (PFAS) are a class of chemicals that were widely used in manufacturing and are now present in the environment throughout the world. It is known that various PFAS are quantifiable in human in blood, but potential adverse health outcomes remain unclear. Sentinel and non-traditional model species are useful to study potential toxicity of PFAS in order to understand the relationship between environmental and human health. Here, we present a critical review of studies on the neurotoxicity of PFAS in sentinel and non-traditional laboratory model systems, including Caenorhabditis elegans (nematode), Dugesia japonica (planarian), Rana pipiens (frogs), Danio rerio and Oryzias melastigma (fish), and Ursus maritimus (polar bears). PFAS have been implicated in developmental neurotoxicity in non-traditional and traditional model systems as well as sentinel species, including effects on neurotransmitter levels, especially acetylcholine and its metabolism. However, further research on the mechanisms of toxicity needs to be conducted to determine if these chemicals are affecting organisms in a similar manner. Overall, findings tend to be similar among the various species, but bioaccumulation may vary, which needs to be taken into account in future studies by quantifying target organ concentrations of PFAS to better compare different species. Furthermore, data on the majority of PFAS is lacking in neurotoxicity testing, and additional studies are needed to corroborate findings thus far.

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Singh, Nalin, and Ching Yi Jennifer Hsieh. "Exploring Potential Carcinogenic Activity of Per- and Polyfluorinated Alkyl Substances Utilizing High-Throughput Toxicity Screening Data." International Journal of Toxicology 40, no. 4 (May 4, 2021): 355–66. http://dx.doi.org/10.1177/10915818211010490.

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Per- and polyfluorinated alkyl substances (PFAS) are ubiquitous, persistent, and toxic chemicals that pose public health risks. Recent carcinogenicity concerns have arisen based on epidemiological studies, animal tumor findings, and mechanistic data. Thousands of PFAS exist; however, current understanding of their toxicity is informed by studies of a select few, namely, perfluorooctanoic acid and perfluorooctanesulfonic acid. Hence, the computational, high-throughput screening tool, the US EPA CompTox Chemical Dashboard’s ToxCast, was utilized to explore the carcinogenicity potential of PFAS. Twenty-three major PFAS that had sufficient in vitro ToxCast data and covered a range of structural subclasses were analyzed with the visual analytics software ToxPi, yielding a qualitative and quantitative assessment of PFAS activity in realms closely linked with carcinogenicity. A comprehensive literature search was also conducted to check the consistency of analyses with other mechanistic data streams. The PFAS were found to induce a vast range of biological perturbations, in line with several of the International Agency for Research on Cancer–defined key carcinogen characteristics. Patterns observed varied by length of fluorine-bonded chains and/or functional group within and between each key characteristic, suggesting some structure-based variability in activity. In general, the major conclusions drawn from the analysis, that is, the most notable activities being modulation of receptor-mediated effects and induction of oxidative stress, were supported by literature findings. The study helps enhance understanding of the mechanistic pathways that underlie the potential carcinogenicity of various PFAS and hence could assist in hazard identification and risk assessment for this emerging and relevant class of environmental toxicants.

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Washington, John W., Charlita G. Rosal, James P. McCord, Mark J. Strynar, Andrew B. Lindstrom, Erica L. Bergman, Sandra M. Goodrow, et al. "Nontargeted mass-spectral detection of chloroperfluoropolyether carboxylates in New Jersey soils." Science 368, no. 6495 (June 4, 2020): 1103–7. http://dx.doi.org/10.1126/science.aba7127.

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The toxicity and environmental persistence of anthropogenic per- and poly-fluoroalkyl substances (PFAS) are of global concern. To address legacy PFAS concerns in the United States, industry developed numerous replacement PFAS that commonly are treated as confidential information. To investigate the distribution of PFAS in New Jersey, soils collected from across the state were subjected to nontargeted mass-spectral analyses. Ten chloroperfluoropolyether carboxylates were tentatively identified, with at least three congeners in all samples. Nine congeners are ≥(CF2)7. Distinct chemical formulas and structures, as well as geographic distribution, suggest airborne transport from an industrial source. Lighter congeners dispersed more widely than heavier congeners, with the most widely dispersed detected in an in-stock New Hampshire sample. Additional data were used to develop a legacy-PFAS fingerprint for historical PFAS sources in New Jersey.

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Britt E. Erickson. "Solvay withheld PFAS toxicity data, group claims." C&EN Global Enterprise 99, no. 5 (February 8, 2021): 15. http://dx.doi.org/10.1021/cen-09905-polcon3.

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Cheryl Hogue. "EPA orders toxicity tests on another PFAS chemical." C&EN Global Enterprise 101, no. 2 (January 16, 2023): 19. http://dx.doi.org/10.1021/cen-10102-polcon4.

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Richter, Lauren, Alissa Cordner, and Phil Brown. "Non-stick science: Sixty years of research and (in)action on fluorinated compounds." Social Studies of Science 48, no. 5 (September 20, 2018): 691–714. http://dx.doi.org/10.1177/0306312718799960.

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Understandings of environmental governance both assume and challenge the relationship between expert knowledge and corresponding action. We explore this interplay by examining the context of knowledge production pertaining to a contested class of chemicals. Per-and polyfluorinated alkyl substances (PFASs) are widely used industrial compounds containing chemical chains of carbon and fluorine that are persistent, bioaccumulative and toxic. Although industry and regulatory scientists have studied the exposure and toxicity concerns of these compounds for decades, and several contaminated communities have documented health concerns as a result of their high levels of exposure, PFAS use remains ubiquitous in a large range of consumer and industrial products. Despite this significant history of industry knowledge production documenting exposure and toxicity concerns, the regulatory approach to PFASs has been limited. This is largely due to a regulatory framework that privileges industry incentives for rapid market entry and trade secret protection over substantive public health protection, creating areas of unseen science, research that is conducted but never shared outside of institutional boundaries. In particular, the risks of PFASs have been both structurally hidden and unexamined by existing regulatory and industry practice. This reveals the uneven pathways that construct issues of social and scientific concern.

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Naidenko, Olga V., David Q. Andrews, Alexis M. Temkin, Tasha Stoiber, Uloma Igara Uche, Sydney Evans, and Sean Perrone-Gray. "Investigating Molecular Mechanisms of Immunotoxicity and the Utility of ToxCast for Immunotoxicity Screening of Chemicals Added to Food." International Journal of Environmental Research and Public Health 18, no. 7 (March 24, 2021): 3332. http://dx.doi.org/10.3390/ijerph18073332.

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The development of high-throughput screening methodologies may decrease the need for laboratory animals for toxicity testing. Here, we investigate the potential of assessing immunotoxicity with high-throughput screening data from the U.S. Environmental Protection Agency ToxCast program. As case studies, we analyzed the most common chemicals added to food as well as per- and polyfluoroalkyl substances (PFAS) shown to migrate to food from packaging materials or processing equipment. The antioxidant preservative tert-butylhydroquinone (TBHQ) showed activity both in ToxCast assays and in classical immunological assays, suggesting that it may affect the immune response in people. From the PFAS group, we identified eight substances that can migrate from food contact materials and have ToxCast data. In epidemiological and toxicological studies, PFAS suppress the immune system and decrease the response to vaccination. However, most PFAS show weak or no activity in immune-related ToxCast assays. This lack of concordance between toxicological and high-throughput data for common PFAS indicates the current limitations of in vitro screening for analyzing immunotoxicity. High-throughput in vitro assays show promise for providing mechanistic data relevant for immune risk assessment. In contrast, the lack of immune-specific activity in the existing high-throughput assays cannot validate the safety of a chemical for the immune system.

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Sinclair, Georgia M., Sara M. Long, Navneet Singh, Timothy L. Coggan, Matthew P. J. Askeland, and Oliver A. H. Jones. "Exposure to Environmentally Relevant Levels of PFAS Causes Metabolic Changes in the Freshwater Amphipod Austrochiltonia subtenuis." Metabolites 12, no. 11 (November 18, 2022): 1135. http://dx.doi.org/10.3390/metabo12111135.

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Per and polyfluoroalkyl substances (PFAS) are of concern to environmental regulators due to their widespread occurrence, persistence and reported toxicity. However, little data exist on the effects of PFAS at environmentally relevant concentrations. The development of molecular markers for PFAS exposure would therefore be useful to better understand the environmental risks of these compounds. In this study, we assessed if such markers could be developed using Gas Chromatography–Mass Spectrometry-based metabolomics. We exposed the freshwater amphipod Austrochiltonia subtenuis to a range of environmentally relevant concentrations of perfluoro-octane sulfonic acid (PFOS), hexafluoropropylene oxide dimer acid (GenX) and perfluorohexanesulphonic acid (PFHxS) for 7 days at five concentrations. A metabolic response was detected in all concentrations and treatments even though the survival rates only differed significantly at the highest exposure levels. The metabolic response differed between compounds but all three PFAS induced changes in the levels of amino acids, fatty acids, and cholesterol, in line with the literature. PFOS was found to bioaccumulate. Both GenX and PFHxS were eliminated from the amphipods, but PFHxS was eliminated at a slower rate than GenX. This information improves our understanding of the sublethal effects of PFAS as well as their environmental fate and behaviour.

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Jiang, Linke, Siqin Wang, Wenzheng Chen, Jiang Lin, Xin Yu, Mingbao Feng, and Kun Wan. "Removal of Per- and Polyfluoroalkyl Substances by Electron Beam and Plasma Irradiation: A Mini-Review." Water 14, no. 11 (May 25, 2022): 1684. http://dx.doi.org/10.3390/w14111684.

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The global prevalence and environmental risks of per- and polyfluoroalkyl substances (PFASs) have caused increasing concern regarding their strategic elimination from aqueous environments. It has recently been recognized that advanced oxidation–reduction technologies (AO/RTs) exhibit superior removal performance for these ubiquitous pollutants. However, the detailed mechanisms and product risks have not been well summarized and systematically deciphered. In this mini-review article, the basic operating principles of two typical AO/RTs (electron beam and plasma irradiation) and their reported applications in the abatement of PFASs are described in detail. It is noteworthy that these reductive treatments induced remarkable defluorination efficiency of PFOA and PFOS with the generation of short-chain congeners in water. The reaction mechanisms mainly included desulfonization, decarboxylation, H/F exchange, radical cyclization, and stepwise losses of CF2 groups. Unexpectedly, partial degradation products manifested high potential in triggering acute and chronic aquatic toxicity, genotoxicity, and developmental toxicity. Additionally, high or even increased resistance to biodegradability was observed for multiple products relative to the parent chemicals. Taken together, both electron beam and plasma irradiation hold great promise in remediating PFAS-contaminated water and wastewater, while the secondary ecological risks should be taken into account during practical applications.

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Cheng, Weixiao, Jon A. Doering, Carlie LaLone, and Carla Ng. "Integrative Computational Approaches to Inform Relative Bioaccumulation Potential of Per- and Polyfluoroalkyl Substances Across Species." Toxicological Sciences 180, no. 2 (January 23, 2021): 212–23. http://dx.doi.org/10.1093/toxsci/kfab004.

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Abstract Predictive toxicology is increasingly reliant on innovative computational methods to address pressing questions in chemicals assessment. Of importance is the evaluation of contaminant impact differences across species to inform ecosystem protection and identify appropriate model species for human toxicity studies. Here we evaluated 2 complementary tools to predict cross-species differences in binding affinity between per- and polyfluoroalkyl substances (PFAS) and the liver fatty acid-binding protein (LFABP): the Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) tool and molecular dynamics (MD). SeqAPASS determined that the structure of human LFABP, a key determinant of PFAS bioaccumulation, was conserved in the majority of vertebrate species, indicating these species would have similar PFAS bioaccumulation potentials. Level 3 SeqAPASS evaluation identified several potentially destabilizing amino acid differences across species, which were generally supported by DUET stability change predictions. Nine single-residue mutations and 7 whole species sequences were selected for MD evaluation. One mutation (F50V for PFNA) showed a statistically significant difference with stronger affinity than wild-type human LFABP. Predicted binding affinities for 9 different PFAS across 7 species showed human, rat, chicken, and rainbow trout had similar binding affinities to one another for each PFAS, whereas Japanese medaka and fathead minnow had significantly weaker LFABP-binding affinity for some PFAS. Based on these analyses, the combined use of SeqAPASS and MD provides rapid screening for potential species differences with deeper structural insight. This approach can be easily extended to other important biological receptors and potential ligands.

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Mojiri, Amin, Mansoureh Nazari Vishkaei, Hanieh Khoshnevis Ansari, Mohammadtaghi Vakili, Hossein Farraji, and Norhafezah Kasmuri. "Toxicity Effects of Perfluorooctanoic Acid (PFOA) and Perfluorooctane Sulfonate (PFOS) on Two Green Microalgae Species." International Journal of Molecular Sciences 24, no. 3 (January 26, 2023): 2446. http://dx.doi.org/10.3390/ijms24032446.

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Amongst per- and polyfluoroalkyl substances (PFAS) compounds, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have a high persistence in physicochemical and biological degradation; therefore, the accumulation of PFOS and PFOA can negatively affect aquatic organisms and human health. In this study, two microalgae species (Chlorella vulgaris and Scenedesmus obliquus) were exposed to different concentrations of a PFOS and PFOA mixture (0 to 10 mg L−1). With increases in the contact time (days) and the PFAS concentration (mg L−1) from 1 to 7, and 0.5 to 10, respectively, the cell viability, total chlorophyll content, and protein content decreased, and the decrease in these parameters was significantly greater in Scenedesmus obliquus. As another step in the study, the response surface methodology (RSM) was used to optimize the toxicity effects of PFAS on microalgae in a logical way, as demonstrated by the high R2 (>0.9). In another stage, a molecular docking study was performed to monitor the interaction of PFOS and PFOA with the microalgae, considering hydrolysis and the enzymes involved in oxidation-reduction reactions using individual enzymes. The analysis was conducted on carboxypeptidase in Chlorella vulgaris and on c-terminal processing protease and oxidized cytochrome c6 in Scenedesmus obliquus. For the enzyme activity, the affinity and dimensions of ligands-binding sites and ligand-binding energy were estimated in each case.

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McCarthy, Christopher J., Shaun A. Roark, and Elizabeth T. Middleton. "Considerations for toxicity experiments and risk assessments with PFAS mixtures." Integrated Environmental Assessment and Management 17, no. 4 (May 13, 2021): 697–704. http://dx.doi.org/10.1002/ieam.4415.

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Kumar, Sachin, Antony Michealraj, Leo Kim, Jeremy Rich, and Michael Taylor. "ETMM-08 METABOLIC REGULATION OF THE EPIGENOME DRIVES LETHAL INFANTILE EPENDYMOMA." Neuro-Oncology Advances 3, Supplement_1 (March 1, 2021): i15—i16. http://dx.doi.org/10.1093/noajnl/vdab024.064.

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Abstract Ependymomas are malignant glial tumours that occur throughout the central nervous system. Of the nine distinct molecular subgroups of ependymoma, Posterior Fossa A (PFA), is the most prevalent, occurring in the hindbrain of infants and young children. Lacking highly recurrent somatic mutations, PFAs are thought to be a largely epigenetically driven entity, defined by hypomethylation at the histone 3 lysine 27 residue. Previous transcriptional analysis of PFAs revealed an enrichment of hypoxia signaling genes. Thus, we hypothesized that hypoxic signaling, in combination with a unique metabolic milieu, drive PFA oncogenesis through epigenetic regulation. In this study, we identified that PFA cells control the availability of specific metabolites under hypoxic conditions, resulting in diminished H3K27 trimethylation and increased H3K27 acetylation in vitro and in vivo. Unique to PFA cells, transient exposure to ambient oxygen results in irreversible cellular toxicity. Furthermore, perturbation of key metabolic pathways is sufficient to inhibit growth of PFA primary cultures in vitro. PFA cells sequester s-adenosylmethionine while upregulating EZHIP, a polycomb repressive complex 2 (PRC2) inhibitor, resulting in decreased H3K27 trimethylation. Furthermore, hypoxia fine-tunes the abundance of alpha-ketoglutarate and acetyl-CoA to fuel demethylase and acetyltransferase activity. Paradoxically, a genome-wide CRISPR knockout screen identified the core components of PRC2 as uniquely essential in PFAs. Our findings suggest that PFAs thrive in a narrow “Goldilocks” zone, whereby they must maintain a unique epigenome and deviation to increased or decreased H3K27 trimethylation results in diminished cellular fitness. Previously, we showed that PFAs have a putative cell of origin arising in the first trimester of development. Using single-cell RNAseq and metabolomics, we demonstrate that PFAs resemble the natural metabolic-hypoxic milieu of normal development. Therefore, targeting metabolism and/or the epigenome presents a unique opportunity for rational therapy for infants with PFA ependymoma.

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Marchetto, Francesca, Marco Roverso, Davide Righetti, Sara Bogialli, Francesco Filippini, Elisabetta Bergantino, and Eleonora Sforza. "Bioremediation of Per- and Poly-Fluoroalkyl Substances (PFAS) by Synechocystis sp. PCC 6803: A Chassis for a Synthetic Biology Approach." Life 11, no. 12 (November 26, 2021): 1300. http://dx.doi.org/10.3390/life11121300.

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One of the main concerns in industrialized countries is represented by per- and poly-fluoroalkyl substances (PFAS), persistent contaminants hardly to be dealt with by conventional wastewater treatment processes. Phyco-remediation was proposed as a green alternative method to treat wastewater. Synechocystis sp. PCC6803 is a unicellular photosynthetic organism candidate for bioremediation approaches based on synthetic biology, as it is able to survive in a wide range of polluted waters. In this work, we assessed the possibility of applying Synechocystis in PFAS-enriched waters, which was never reported in the previous literature. Respirometry was applied to evaluate short-term toxicity of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), which did not affect growth up to 0.5 and 4 mg L−1, respectively. Continuous and batch systems were used to assess the long-term effects, and no toxicity was highlighted for both compounds at quite high concentration (1 mg L−1). A partial removal was observed for PFOS and PFOA, (88% and 37%, with removal rates of about 0.15 and 0.36 mg L−1 d−1, respectively). Measurements in fractionated biomass suggested a role for Synechocystis in the sequestration of PFAS: PFOS is mainly internalized in the cell, while PFOA is somehow transformed by still unknown pathways. A preliminary bioinformatic search gave hints on transporters and enzymes possibly involved in such sequestration/transformation processes, opening the route to metabolic engineering in the perspective application of this cyanobacterium as a new phyco-remediation tool, based on synthetic biology.

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Kannan, Kurunthachalam. "Perfluoroalkyl and polyfluoroalkyl substances: current and future perspectives." Environmental Chemistry 8, no. 4 (2011): 333. http://dx.doi.org/10.1071/en11053.

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Environmental contextPerfluoroalkyl substances were recognised as global environmental pollutants 10 years ago. Although considerable advancements have been made in our understanding of the environmental distribution, fate and toxicity of perfluoroalkyl substances, several important issues remain to be resolved. This article identifies existing knowledge gaps that deserve further investigations to enable meaningful regulatory decisions. AbstractIt has been over a decade since perfluoroalkyl substances (PFASs) were discovered as global environmental contaminants. Considerable progress has been made in our understanding of the environmental fate and toxic effects of PFASs since then. Government regulations and voluntary emission reduction initiatives by industry have been effective in reducing environmental and human exposure to a major PFAS, perfluorooctane sulfonate (PFOS), in the United States and several other western countries. Although significant advances have been made in our understanding of the environmental chemistry of PFASs, considerable knowledge gaps still exist in several areas of environmental fate and risk assessments. Owing to their complex chemistry, involving existence of multiple precursors with significant numbers of structural isomers and mixtures of homologues, multiple degradation pathways and unique physicochemical properties, challenges remain in elucidating sources and environmental fate. In this overview, some of the knowledge gaps in PFASs’ research have been identified and suggestions for future research have been made.

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Jabeen, Musarrat, Muhammad Fayyaz, and Joseph Irudayaraj. "Epigenetic Modifications, and Alterations in Cell Cycle and Apoptosis Pathway in A549 Lung Carcinoma Cell Line upon Exposure to Perfluoroalkyl Substances." Toxics 8, no. 4 (November 23, 2020): 112. http://dx.doi.org/10.3390/toxics8040112.

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Per- and polyfluoroalkyl substances (PFAS) are a group of human-made compounds with strong C-F bonds, and have been used in various manufacturing industries for decades. PFAS have been reported to deleterious effect on human health, which has led to studies identifying the possible toxicity and toxicity routes of these compounds. We report that these compounds have the potential to cause epigenetic modifications, and to induce dysregulation in the cell proliferation cycle as well as apoptosis in A549 lung cancer cells when exposed to 10-, 200- and 400 μM concentrations of each compound. Our studies show that exposure to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) may cause hypomethylation in the epigenome, but changes in the epigenetic makeup are not evident upon exposure to GenX. We establish that exposure to lower doses of these compounds causes the cells’ balance to shift to cell proliferation, whereas exposure to higher concentrations shifts the balance more towards apoptosis. Furthermore, the apoptosis pathway upon exposure to GenX, PFOA, and PFOS has also been identified. Our findings suggest that exposure to any of these compounds may have profound effects in patients with pre-existing lung conditions or could trigger lung cancinogenesis.

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Wu, Xiaoqin, Helen Nguyen, Damian Kim, and Hui Peng. "Chronic toxicity of PFAS-free AFFF alternatives in terrestrial plant Brassica rapa." Science of The Total Environment 850 (December 2022): 158100. http://dx.doi.org/10.1016/j.scitotenv.2022.158100.

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Michealraj, Antony, Sachin Kumar, Leo Kim, Jeremy Rich, and Michael Taylor. "TAMI-59. METABOLIC REGULATION OF THE EPIGENOME DRIVES LETHAL INFANTILE EPENDYMOMA." Neuro-Oncology 22, Supplement_2 (November 2020): ii226. http://dx.doi.org/10.1093/neuonc/noaa215.946.

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Abstract Ependymomas are malignant glial tumors that occur throughout the central nervous system. Of the nine distinct molecular types of ependymoma, Posterior Fossa A(PFA) ependymomas, found in the hindbrain of infants and young children, are the most prevalent type. They rarely harbor recurrent somatic single nucleotide or copy number aberrations, but rather display epigenetic dysregulations. Transcriptional analyses show that PFAs, but not other molecular ependymoma variants, have elevated hypoxic signaling. We hypothesized that the metabolic environment of the developing human fetal hindbrain contributes to PFA ependymomas through the intermediary metabolic mechanism. Hypoxia microenvironment is essential for PFA survival and upholding their epigenetic dysregulation. Hypoxia blocks methyltransferase activity by upregulating EZHIPs expression and restricting SAM abundance. Fine-tuning the abundance of a-KG and acetyl-CoA, hypoxia fuels demethylase, and acetyltransferase activity which collectively resulting in H3K27 hypomethylation and hyperacetylation. Genome-wide essentially screen further underscore that minimal basal level of H3K27me3 is essential for PFA survival and further attenuation of H3K27me3 decreases the fitness of PFAs. PFA Ependymomas have a unique epigenome, suggesting a model in which they thrive in a narrow Goldilocks zone, with deviation to either increased or decreased H3K27me3 levels leading to diminished cellular fitness. PFAs are maintained under hypoxia, associated with restricted availability of specific metabolites to diminish histone methylation and increase histone demethylation and acetylation at H3K27. PFAs initiate from a cell lineage in the first trimester of human development that resides in restricted oxygen. Unlike other ependymomas, transient exposure of PFA cells to ambient oxygen induces irreversible cellular toxicity. PFA tumors exhibit a low basal level of H3K27me3 and, paradoxically, inhibition of H3K27 methylation specifically disrupts PFA growth. Microenvironmental regulation of PFA ependymoma epigenome appears to play a major role in tumorigenesis. Targeting metabolism and/or the epigenome presents a unique opportunity for rational therapy for infants with PFA ependymoma.

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Truong, Lisa, Yvonne Rericha, Preethi Thunga, Skylar Marvel, Dylan Wallis, Michael T. Simonich, Jennifer A. Field, Dunping Cao, David M. Reif, and Robyn L. Tanguay. "Systematic developmental toxicity assessment of a structurally diverse library of PFAS in zebrafish." Journal of Hazardous Materials 431 (June 2022): 128615. http://dx.doi.org/10.1016/j.jhazmat.2022.128615.

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Wang, Xiaoping, Jasmin Schuster, Kevin C. Jones, and Ping Gong. "Occurrence and spatial distribution of neutral perfluoroalkyl substances and cyclic volatile methylsiloxanes in the atmosphere of the Tibetan Plateau." Atmospheric Chemistry and Physics 18, no. 12 (June 21, 2018): 8745–55. http://dx.doi.org/10.5194/acp-18-8745-2018.

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Abstract. Due to their properties of bioaccumulation, toxicity, and long-range atmospheric transport, polyfluoroalkyl and perfluoroalkyl substances (PFASs) and cyclic volatile methylsiloxanes (cVMSs) are currently being considered as emerging persistent organic pollutants (POPs) for regulation. To date, there are limited data on PFASs and cVMSs in the atmosphere of the Tibetan Plateau (TP), a remote environment which can provide information on global background conditions. Sorbent-impregnated polyurethane foam (SIP) disc passive air samplers were therefore deployed for 3 months (May to July 2011 and 2013) at 16 locations across the TP. Using previously reported methods for estimating the air volume sampled by SIP discs, the derived atmospheric concentrations ranged as follows: 18–565 ng m−3 for ΣcVMS (including D3, D4, D5, and D6); 65–223 pg m−3 for fluorotelomer alcohols (ΣFTOHs); 1.2–12.8 pg m−3 for fluorinated sulfonamides (ΣFOSA); and 0.29–1.02 pg m−3 for fluorinated sulfonamidoethanols (ΣFOSE). The highest ΣcVMS occurred at Lhasa, the capital city of the TP, indicating the local contribution to the emerging pollutants. Higher levels of ΣFTOHs were observed at sites close to the transport channel of the Yarlung Tsangpo Grand Canyon, indicating possible long-range atmospheric transport (LRAT). Elevated concentrations of shorter-chain volatile PFAS precursors (4 : 2 FTOH and fluorobutane sulfonamidoethanol) were found in most air samples, reflecting the shift in production from long- to short-chain PFASs in Asia. Overall, concentrations of emerging POPs at background sites of the TP were 1–3 orders of magnitude higher than those reported for legacy POPs.

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Sznajder-Katarzyńska, Katarzyna, Magdalena Surma, and Iwona Cieślik. "A Review of Perfluoroalkyl Acids (PFAAs) in terms of Sources, Applications, Human Exposure, Dietary Intake, Toxicity, Legal Regulation, and Methods of Determination." Journal of Chemistry 2019 (June 12, 2019): 1–20. http://dx.doi.org/10.1155/2019/2717528.

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Per- and polyfluoroalkyl substances (PFASs) are widely distributed across the world and are expected to be of concern to human health and the environment. The review focuses on perfluoroalkyl acids (PFAAs) and, in particular, on the most frequently discussed perfluoroalkyl carboxylic acids (PFCAs) and perfluoroalkane sulfonic acids (PFSAs). In this study, some basic information concerning PFASs is reviewed, focusing mainly on PFAAs (perfluoroalkyl acids). We have made efforts to systemize their division into groups according to chemical structure, describe their basic physicochemical properties, characterize production technologies, and determine potential human exposure routes with particular reference to oral exposure. A variety of possible toxicological effects to human health are also discussed. In response to increasing public concern about the toxicity of PFAAs, an evaluation of dietary intake has been undertaken for two of the most commonly known PFAAs: perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS). As summarized in this study, PFAAs levels need further assessment due to the science-based TWI standards laid down by the EFSA’s CONTAM Panel regarding the risk to human health posed by the presence of perfluorooctane sulfonic acid and perfluorooctanoic acid in food (tolerable weekly intakes of PFOA and PFOS set up to 6 ng·kg−1·bw·week−1 and 13 ng·kg−1·bw·week−1, respectively). Current legislation, relevant legislation on PFAAs levels in food, and the most popular methods of analysis in food matrices are described.

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Liu, Xianglin, Xiaowei Zheng, Liangliang Zhang, Jue Li, Yanyao Li, Honghui Huang, and Zhengqiu Fan. "Joint toxicity mechanisms of binary emerging PFAS mixture on algae (Chlorella pyrenoidosa) at environmental concentration." Journal of Hazardous Materials 437 (September 2022): 129355. http://dx.doi.org/10.1016/j.jhazmat.2022.129355.

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Woodlief, Tracey, Samuel Vance, Qing Hu, and Jamie DeWitt. "Immunotoxicity of Per- and Polyfluoroalkyl Substances: Insights into Short-Chain PFAS Exposure." Toxics 9, no. 5 (May 1, 2021): 100. http://dx.doi.org/10.3390/toxics9050100.

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Novel per- and polyfluoroalkyl substances (PFAS) were recently identified in drinking water sources throughout North Carolina. These include the perfluoroether acids (PFEAs) perfluoro-2-methoxyacetic acid (PFMOAA), perfluoro-2-methoxypropanoic acid (PFMOPrA), and perfluoro-4-methoxybutanioc acid (PFMOBA). Little toxicological data exist for these PFEAs. Therefore, the present study described signs of toxicity and immunotoxicity following oral exposure. Adult male and female C57BL/6 mice were exposed once/day for 30 days to PFMOAA (0, 0.00025, 0.025, or 2.5 mg/kg), PFMOPrA, or PFMOBA (0, 0.5, 5, or 50 mg/kg). A dose of 7.5 mg/kg of perfluorooctanoic acid (PFOA) was used as a positive control. Terminal body weights, and absolute liver, spleen, or thymus weights did not differ by dose for any compound; exposure to 50 mg/kg of PFMOBA increased relative liver weights in males. Changes in splenic cellularity were observed in males exposed to PFMOPrA and decreased numbers of B and natural killer (NK) cells were observed in males and females exposed to PFMOBA. Exposure did not alter NK cell cytotoxicity or T cell-dependent antibody responses at doses administered. Our results indicate that these “understudied” PFAS have toxicological potential but require additional investigation across endpoints and species, including humans, to understand health effects via drinking water exposure.

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Houck, Keith A., Grace Patlewicz, Ann M. Richard, Antony J. Williams, Mahmoud A. Shobair, Marci Smeltz, M. Scott Clifton, Barbara Wetmore, Alex Medvedev, and Sergei Makarov. "Bioactivity profiling of per- and polyfluoroalkyl substances (PFAS) identifies potential toxicity pathways related to molecular structure." Toxicology 457 (June 2021): 152789. http://dx.doi.org/10.1016/j.tox.2021.152789.

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Presentato, Alessandro, Silvia Lampis, Andrea Vantini, Flavio Manea, Francesca Daprà, Stefano Zuccoli, and Giovanni Vallini. "On the Ability of Perfluorohexane Sulfonate (PFHxS) Bioaccumulation by Two Pseudomonas sp. Strains Isolated from PFAS-Contaminated Environmental Matrices." Microorganisms 8, no. 1 (January 9, 2020): 92. http://dx.doi.org/10.3390/microorganisms8010092.

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PFASs (perfluoroalkyl and polyfluoroalkyl substances) are highly fluorinated, aliphatic, synthetic compounds with high thermal and chemical stability as well as unique amphiphilic properties which make them ingredients in a range of industrial processes. PFASs have attracted consideration due to their persistence, toxicity and bioaccumulation tendency in the environment. Recently, attention has begun to be addressed to shorter-chain PFASs, such as perfluorohexane sulfonate [PFHxS], apparently less toxic to and more easily eliminated from lab animals. However, short-chain PFASs represent end-products from the transformation of fluorotelomers whose biotic breakdown reactions have not been identified to date. This means that such emergent pollutants will tend to accumulate and persist in ecosystems. Since we are just learning about the interaction between short-chain PFASs and microorganisms, this study reports on the response to PFHxS of two Pseudomonas sp. strains isolated from environmental matrices contaminated by PFASs. The PFHxS bioaccumulation potential of these strains was unveiled by exploiting different physiological conditions as either axenic or mixed cultures under alkanothrofic settings. Moreover, electron microscopy revealed nonorthodox features of the bacterial cells, as a consequence of the stress caused by both organic solvents and PFHxS in the culturing substrate.

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Gaballah, Shaza, Adam Swank, Jon R. Sobus, Xia Meng Howey, Judith Schmid, Tara Catron, James McCord, Erin Hines, Mark Strynar, and Tamara Tal. "Evaluation of Developmental Toxicity, Developmental Neurotoxicity, and Tissue Dose in Zebrafish Exposed to GenX and Other PFAS." Environmental Health Perspectives 128, no. 4 (April 2020): 047005. http://dx.doi.org/10.1289/ehp5843.

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Cui, Danni, Xuerong Li, and Natalia Quinete. "Occurrence, fate, sources and toxicity of PFAS: What we know so far in Florida and major gaps." TrAC Trends in Analytical Chemistry 130 (September 2020): 115976. http://dx.doi.org/10.1016/j.trac.2020.115976.

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Hoyeck, Myriam P., Geronimo Matteo, Erin M. MacFarlane, Ineli Perera, and Jennifer E. Bruin. "Persistent organic pollutants and β-cell toxicity: a comprehensive review." American Journal of Physiology-Endocrinology and Metabolism 322, no. 5 (May 1, 2022): E383—E413. http://dx.doi.org/10.1152/ajpendo.00358.2021.

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Persistent organic pollutants (POPs) are a diverse family of contaminants that show widespread global dispersion and bioaccumulation. Humans are continuously exposed to POPs through diet, air particles, and household and commercial products; POPs are consistently detected in human tissues, including the pancreas. Epidemiological studies show a modest but consistent correlation between exposure to POPs and increased diabetes risk. The goal of this review is to provide an overview of epidemiological evidence and an in-depth evaluation of the in vivo and in vitro evidence that POPs cause β-cell toxicity. We review evidence for six classes of POPs: dioxins, polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), organophosphate pesticides (OPPs), flame retardants, and per- and polyfluoroalkyl substances (PFAS). The available data provide convincing evidence implicating POPs as a contributing factor driving impaired glucose homeostasis, β-cell dysfunction, and altered metabolic and oxidative stress pathways in islets. These findings support epidemiological data showing that POPs increase diabetes risk and emphasize the need to consider the endocrine pancreas in toxicity assessments. Our review also highlights significant gaps in the literature assessing islet-specific endpoints after both in vivo and in vitro POP exposure. In addition, most rodent studies do not consider the impact of biological sex or secondary metabolic stressors in mediating the effects of POPs on glucose homeostasis and β-cell function. We discuss key gaps and limitations that should be assessed in future studies.

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Patlewicz, Grace, Ann M. Richard, Antony J. Williams, Christopher M. Grulke, Reeder Sams, Jason Lambert, Pamela D. Noyes, et al. "A Chemical Category-Based Prioritization Approach for Selecting 75 Per- and Polyfluoroalkyl Substances (PFAS) for Tiered Toxicity and Toxicokinetic Testing." Environmental Health Perspectives 127, no. 1 (January 2019): 014501. http://dx.doi.org/10.1289/ehp4555.

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41

Gałęzowska, Grażyna, Justyna Rogowska, Ewa Olkowska, Wojciech Ratajczyk, and Lidia Wolska. "Environmental Risk Assessment Resulting from Sediment Contamination with Perfluoroalkyl Substances." Molecules 26, no. 1 (December 29, 2020): 116. http://dx.doi.org/10.3390/molecules26010116.

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Due to wide use of perfluoroalkyl substances (PFASs) (e.g., in metal-plating, in fire-fighting foam, lubricants) and their resistance to degradation, they occur widely in the environment. The aim of this study was to estimate the environmental risk resulting from the presence of PFASs in the Gulf of Gdansk. Therefore, 17 PFASs concentrations were determined using ultra performance liquid chromatography with tandem mass spectrometry detection (UPLC-MS/MS). Additionally, sediment ecotoxicity was investigated. The results of the chemical analysis were used to asses environmental risk of PFASs. In samples collected around discharge collectors from a wastewater treatment plant and the Vistula mouth, Σ17PFASs values were 0.00403 ÷ 40.6 and 0.509 ÷ 614 ng/g d.w., respectively. In samples collected around discharge collectors, PFHxA, PFPeA, PFHpA, and PFOA were dominating, while at the Vistula River mouth, PFHxS, PFDS, and PFBS were prevalent. For most sediments, no toxic effect was observed in the toxicity tests with Heterocypris inconguens and Aliivibrio ficsheri. There was no observed correlation between the PFASs level and their ecotoxicity. Generally, the results of environmental risk assessment indicate that the PFASs would not generate high impact on the aquatic life (five water samples have shown medium risk related to PFBS and PFDoA).

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Kumar, Sachin, Antony Michealraj, Leo Kim, Jeremy Rich, and Michael Taylor. "EPEN-52. METABOLIC REGULATION OF THE EPIGENOME DRIVES LETHAL INFANTILE EPENDYMOMA." Neuro-Oncology 22, Supplement_3 (December 1, 2020): iii318. http://dx.doi.org/10.1093/neuonc/noaa222.185.

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Abstract PFA ependymomas are a lethal glial malignancy of the hindbrain found in infants and toddlers. Lacking any highly recurrent somatic mutations, PFAs have been proposed to be a largely epigenetically driven entity, defined by hypomethylation at the histone 3 lysine 27 residue. Unfortunately, an almost complete lack of model systems has limited the discovery of novel PFA therapies. In this study, we have identified that the PFA hypoxic microenvironment controls the availability of specific metabolites, resulting in diminished H3K27 trimethylation and increased H3K27 acetylation in vitro and in vivo. Unique to PFA cells, transient exposure to ambient oxygen results in irreversible cellular toxicity. Furthermore, perturbation of key metabolic pathways is sufficient to inhibit growth of PFA primary cultures in vitro. Although PFA tumors exhibit a low basal level of H3K27me3, inhibition of H3K27 methylation paradoxically demonstrates significant and specific activity against PFA. Thus, we propose a “Goldilocks Model” of metabolic-epigenetic regulation in PFA ependymoma, whereby increased or decreased H3K27 trimethylation results in cell death. Mapping of PFA ependymoma tumours suggests a cell of origin arising in the first trimester of human development where there is a known hypoxic microenvironment. Therefore, targeting metabolism and/or the epigenome presents a unique opportunity for rational therapy for infants with PFA ependymoma.

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Podder, Aditi, A. H. M. Anwar Sadmani, Debra Reinhart, Ni-Bin Chang, and Ramesh Goel. "Per and poly-fluoroalkyl substances (PFAS) as a contaminant of emerging concern in surface water: A transboundary review of their occurrences and toxicity effects." Journal of Hazardous Materials 419 (October 2021): 126361. http://dx.doi.org/10.1016/j.jhazmat.2021.126361.

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Kanchanapiya, Premrudee, Supachai Songngam, and Thanapol Tantisattayakul. "The Adsorption of Perfluorooctanoic Acid on Coconut Shell Activated Carbons." AIMS Environmental Science 9, no. 2 (2022): 128–39. http://dx.doi.org/10.3934/environsci.2022010.

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<abstract> <p>Perfluorooctanoic acid (PFOA) is one of Per- and polyfluoroalkyl substances (PFAS) that have increasingly attracted concerns due to their global distribution in environment, persistence, high bioaccumulation and toxicity. It is important to study the effective treatment to remove PFOA from contaminated water. The feasibility of using commercial coconut shell activated carbon produced in Thailand to remove PFOA from water was investigated with regard to their adsorption kinetics and isotherms of powder activated carbon (PAC-325) and granular activated carbon (GAC-20x50). Adsorption kinetic results show that the adsorbent size significantly affected the adsorption rate of PFOA, and GAC-20x50 required at least 100 h to achieve the equilibrium, much longer than 3 h for PAC-325. Two kinetic models were fitted to the experimental data, and the pseudo-second-order model well described the adsorption of PFOA on both PAC-325 and GAC-20x50. PAC-325 trended to adsorb PFOA faster than GAC-20x50 and testing with the shortest adsorption times (5 min) still yielded substantial PFOA removal (~80% for PAC-325). The adsorption isotherms show that the adsorption capacity of PAC-325 was 0.80 mmol/g, which is 83 % higher than that for GAC-20x50 (0.13 mmol/g), according to the Langmuir fitting.</p> </abstract>

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Kanchanapiya, Premrudee, Supachai Songngam, and Thanapol Tantisattayakul. "The Adsorption of Perfluorooctanoic Acid on Coconut Shell Activated Carbons." AIMS Environmental Science 9, no. 2 (2022): 112–23. http://dx.doi.org/10.3934/environsci.20220010.

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<abstract> <p>Perfluorooctanoic acid (PFOA) is one of Per- and polyfluoroalkyl substances (PFAS) that have increasingly attracted concerns due to their global distribution in environment, persistence, high bioaccumulation and toxicity. It is important to study the effective treatment to remove PFOA from contaminated water. The feasibility of using commercial coconut shell activated carbon produced in Thailand to remove PFOA from water was investigated with regard to their adsorption kinetics and isotherms of powder activated carbon (PAC-325) and granular activated carbon (GAC-20x50). Adsorption kinetic results show that the adsorbent size significantly affected the adsorption rate of PFOA, and GAC-20x50 required at least 100 h to achieve the equilibrium, much longer than 3 h for PAC-325. Two kinetic models were fitted to the experimental data, and the pseudo-second-order model well described the adsorption of PFOA on both PAC-325 and GAC-20x50. PAC-325 trended to adsorb PFOA faster than GAC-20x50 and testing with the shortest adsorption times (5 min) still yielded substantial PFOA removal (~80% for PAC-325). The adsorption isotherms show that the adsorption capacity of PAC-325 was 0.80 mmol/g, which is 83 % higher than that for GAC-20x50 (0.13 mmol/g), according to the Langmuir fitting.</p> </abstract>

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Souckova, Olga, Vaclava Skopova, Veronika Baresova, David Sedlak, Anthony J. Bleyer, Stanislav Kmoch, and Marie Zikanova. "Metabolites of De Novo Purine Synthesis: Metabolic Regulators and Cytotoxic Compounds." Metabolites 12, no. 12 (December 2, 2022): 1210. http://dx.doi.org/10.3390/metabo12121210.

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Cytotoxicity of de novo purine synthesis (DNPS) metabolites is critical to the pathogenesis of three known and one putative autosomal recessive disorder affecting DNPS. These rare disorders are caused by biallelic mutations in the DNPS genes phosphoribosylformylglycineamidine synthase (PFAS), phosphoribosylaminoimidazolecarboxylase/phosphoribosylaminoimidazolesuccinocarboxamide synthase (PAICS), adenylosuccinate lyase (ADSL), and aminoimidazole carboxamide ribonucleotide transformylase/inosine monophosphate cyclohydrolase (ATIC) and are clinically characterized by developmental abnormalities, psychomotor retardation, and nonspecific neurological impairment. At a biochemical level, loss of function of specific mutated enzymes results in elevated levels of DNPS ribosides in body fluids. The main pathogenic effect is attributed to the accumulation of DNPS ribosides, which are postulated to be toxic to the organism. Therefore, we decided to characterize the uptake and flux of several DNPS metabolites in HeLa cells and the impact of DNPS metabolites to viability of cancer cell lines and primary skin fibroblasts. We treated cells with DNPS metabolites and followed their flux in purine synthesis and degradation. In this study, we show for the first time the transport of formylglycinamide ribotide (FGAR), aminoimidazole ribotide (AIR), succinylaminoimidazolecarboxamide ribotide (SAICAR), and aminoimidazolecarboxamide ribotide (AICAR) into cells and their flux in DNPS and the degradation pathway. We found diminished cell viability mostly in the presence of FGAR and AIR. Our results suggest that direct cellular toxicity of DNPS metabolites may not be the primary pathogenetic mechanism in these disorders.

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Balaguer-Trias, Jordina, Deepika Deepika, Marta Schuhmacher, and Vikas Kumar. "Impact of Contaminants on Microbiota: Linking the Gut–Brain Axis with Neurotoxicity." International Journal of Environmental Research and Public Health 19, no. 3 (January 26, 2022): 1368. http://dx.doi.org/10.3390/ijerph19031368.

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Over the last years, research has focused on microbiota to establish a missing link between neuronal health and intestine imbalance. Many studies have considered microbiota as critical regulators of the gut–brain axis. The crosstalk between microbiota and the central nervous system is mainly explained through three different pathways: the neural, endocrine, and immune pathways, intricately interconnected with each other. In day-to-day life, human beings are exposed to a wide variety of contaminants that affect our intestinal microbiota and alter the bidirectional communication between the gut and brain, causing neuronal disorders. The interplay between xenobiotics, microbiota and neurotoxicity is still not fully explored, especially for susceptible populations such as pregnant women, neonates, and developing children. Precisely, early exposure to contaminants can trigger neurodevelopmental toxicity and long-term diseases. There is growing but limited research on the specific mechanisms of the microbiota–gut–brain axis (MGBA), making it challenging to understand the effect of environmental pollutants. In this review, we discuss the biological interplay between microbiota–gut–brain and analyse the role of endocrine-disrupting chemicals: Bisphenol A (BPA), Chlorpyrifos (CPF), Diethylhexyl phthalate (DEHP), and Per- and polyfluoroalkyl substances (PFAS) in MGBA perturbations and subsequent neurotoxicity. The complexity of the MGBA and the changing nature of the gut microbiota pose significant challenges for future research. However, emerging in-silico models able to analyse and interpret meta-omics data are a promising option for understanding the processes in this axis and can help prevent neurotoxicity.

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Barbosa, Marta O., Nuno Ratola, Vera Homem, M. Fernando R. Pereira, Adrián M. T. Silva, Ana R. L. Ribeiro, Marta Llorca, and Marinella Farré. "Per- and Poly-Fluoroalkyl Substances in Portuguese Rivers: Spatial-Temporal Monitoring." Molecules 28, no. 3 (January 26, 2023): 1209. http://dx.doi.org/10.3390/molecules28031209.

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Eighteen per-and polyfluoroalkyl substances (PFASs) were investigated in surface waters of four river basins in Portugal (Ave, Leça, Antuã, and Cértima) during the dry and wet seasons. All sampling sites showed contamination in at least one of the seasons. In the dry season, perfluorooctanoate acid (PFOA) and perfluoro-octane sulfonate (PFOS), were the most frequent PFASs, while during the wet season these were PFOA and perfluobutane-sulfonic acid (PFBS). Compounds detected at higher concentrations were PFOS (22.6 ng L−1) and perfluoro-butanoic acid (PFBA) (22.6 ng L−1) in the dry and wet seasons, respectively. Moreover, the prospective environmental risks of PFASs, detected at higher concentrations, were evaluated based on the Risk Quotient (RQ) classification, which comprises acute and chronic toxicity. The results show that the RQ values of eight out of the nine PFASs were below 0.01, indicating low risk to organisms at different trophic levels in the four rivers in both seasons, wet and dry. Nevertheless, in the specific case of perfluoro-tetradecanoic acid (PFTeA), the RQ values calculated exceeded 1 for fish (96 h) and daphnids (48 h), indicating a high risk for these organisms. Furthermore, the RQ values were higher than 0.1, indicating a medium risk for fish, daphnids and green algae (96 h).

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Cai, Yanping, Haiyan Chen, Huilun Chen, Haiqing Li, Shuo Yang, and Fei Wang. "Evaluation of Single and Joint Toxicity of Perfluorinated Carboxylic Acids and Copper to Metal-Resistant Arthrobacter Strains." International Journal of Environmental Research and Public Health 16, no. 1 (January 7, 2019): 135. http://dx.doi.org/10.3390/ijerph16010135.

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Perfluorocarboxylic acid compounds (PFCAs) and copper have been regarded as ubiquitous environmental contaminants in aquatic ecosystems worldwide. However, data on their possible joint toxic effects on microorganisms are still lacking. To study the combined effects of four PFCAs with different carbon chain lengths and copper, a series of experiments were conducted to explore the acute toxicity of these PFCAs in the absence and presence of copper on a metal-resistant Arthrobacter strain GQ-9 by microcalorimetry. The thermokinetic parameters, including growth rate constant (k), inhibitory ratio (I), and half inhibitory concentration (IC50), were calculated and compared using the data obtained from the power-time curves. Our work revealed that GQ-9 is more resistant to perfluorooctanoic acid (PFOA) than Escherichia coli. The single and joint toxicity of PFCAs with copper are dose- and carbon chain length-dependent. The longer the carbon chain length of PFCAs, the higher the toxicity. In addition, PFCAs interacted synergistically with copper. This work could provide useful information for the risk assessment of co-exposure to perfluorinated compounds and heavy metals in natural environments.

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Goodrich, Jaclyn M., Miriam M. Calkins, Alberto J. Caban-Martinez, Todd Stueckle, Casey Grant, Antonia M. Calafat, Amy Nematollahi, et al. "Per- and polyfluoroalkyl substances, epigenetic age and DNA methylation: a cross-sectional study of firefighters." Epigenomics 13, no. 20 (October 2021): 1619–36. http://dx.doi.org/10.2217/epi-2021-0225.

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Background: Per- and polyfluoroalkyl substances (PFASs) are persistent chemicals that firefighters encounter. Epigenetic modifications, including DNA methylation, could serve as PFASs toxicity biomarkers. Methods: With a sample size of 197 firefighters, we quantified the serum concentrations of nine PFASs, blood leukocyte DNA methylation and epigenetic age indicators via the EPIC array. We examined the associations between PFASs with epigenetic age, site- and region-specific DNA methylation, adjusting for confounders. Results: Perfluorohexane sulfonate, perfluorooctanoate (PFOA) and the sum of branched isomers of perfluorooctane sulfonate (Sm-PFOS) were associated with accelerated epigenetic age. Branched PFOA, linear PFOS, perfluorononanoate, perfluorodecanoate and perfluoroundecanoate were associated with differentially methylated loci and regions. Conclusion: PFASs concentrations are associated with accelerated epigenetic age and locus-specific DNA methylation. The implications for PFASs toxicity merit further investigation.

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Journal articles on the topic 'PFAS toxicity'

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