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      Survival, Growth, and Reproduction Responses in a Three-Generation Exposure of the Zebrafish ( Danio rerio) to Perfluorooctane Sulfonate

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          Abstract

          A prior multigenerational perfluorooctane sulfonic acid (PFOS) exposure investigation in zebrafish reported adverse effects at 0.734 μg/L, among the lowest aquatic effect levels for PFOS reported to date. The present three-generation PFOS exposure quantified survival, growth, reproduction, and vitellogenin (VTG; egg yolk protein) responses in zebrafish, incorporating experimental design and procedural improvements relative to the earlier study. Exposures targeting 0.1, 0.6, 3.2, 20, and 100 μg/L in parental (P) and first filial (F1) generations lasted for 180 days post fertilization (dpf) and the second filial generation (F2) through 16 dpf. Survival decreased significantly in P and F2 generation exposures, but not in F1, at the highest PFOS treatment (100 μg/L nominal, 94–205 μg/L, measured). Significant adverse effects on body weight and length were infrequent, of low magnitude, and occurred predominantly at the highest exposure treatment. Finally, PFOS had no significant effects on P or F1 egg production and survival or whole-body VTG levels in P or F1 male fish. Overall, the predominance and magnitude of adverse PFOS effects at <1 μg/L reported in prior research were largely nonrepeatable in the present study. In contrast, the present study indicated a threshold for ecologically relevant adverse effects in zebrafish at 117 μg/L (SE 8 μg/L, n = 10) for survival and 47 μg/L (SE 11 μg/L, n = 19) for all statistically significant negative effects observed.

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          A Review of the Pathways of Human Exposure to Poly- and Perfluoroalkyl Substances (PFASs) and Present Understanding of Health Effects

          Here we review present understanding of sources and trends in human exposure to poly- and perfluoroalkyl substances (PFASs) and epidemiologic evidence for impacts on cancer, immune function, metabolic outcomes, and neurodevelopment. More than 4000 PFASs have been manufactured by humans and hundreds have been detected in environmental samples. Direct exposures due to use in products can be quickly phased out by shifts in chemical production but exposures driven by PFAS accumulation in the ocean and marine food chains and contamination of groundwater persist over long timescales. Serum concentrations of legacy PFASs in humans are declining globally but total exposures to newer PFASs and precursor compounds have not been well characterized. Human exposures to legacy PFASs from seafood and drinking water are stable or increasing in many regions, suggesting observed declines reflect phase-outs in legacy PFAS use in consumer products. Many regions globally are continuing to discover PFAS contaminated sites from aqueous film forming foam (AFFF) use, particularly next to airports and military bases. Exposures from food packaging and indoor environments are uncertain due to a rapidly changing chemical landscape where legacy PFASs have been replaced by diverse precursors and custom molecules that are difficult to detect. Multiple studies find significant associations between PFAS exposure and adverse immune outcomes in children. Dyslipidemia is the strongest metabolic outcome associated with PFAS exposure. Evidence for cancer is limited to manufacturing locations with extremely high exposures and insufficient data are available to characterize impacts of PFAS exposures on neurodevelopment. Preliminary evidence suggests significant health effects associated with exposures to emerging PFASs. Lessons learned from legacy PFASs indicate that limited data should not be used as a justification to delay risk mitigation actions for replacement PFASs.
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            Per‐ and Polyfluoroalkyl Substance Toxicity and Human Health Review: Current State of Knowledge and Strategies for Informing Future Research

            Reports of environmental and human health impacts of per- and polyfluoroalkyl substances (PFAS) have greatly increased in the peer-reviewed literature. The goals of the present review are to assess the state of the science regarding toxicological effects of PFAS and to develop strategies for advancing knowledge on the health effects of this large family of chemicals. Currently, much of the toxicity data available for PFAS are for a handful of chemicals, primarily legacy PFAS such as perfluorooctanoic acid and perfluorooctane sulfonate. Epidemiological studies have revealed associations between exposure to specific PFAS and a variety of health effects, including altered immune and thyroid function, liver disease, lipid and insulin dysregulation, kidney disease, adverse reproductive and developmental outcomes, and cancer. Concordance with experimental animal data exists for many of these effects. However, information on modes of action and adverse outcome pathways must be expanded, and profound differences in PFAS toxicokinetic properties must be considered in understanding differences in responses between the sexes and among species and life stages. With many health effects noted for a relatively few example compounds and hundreds of other PFAS in commerce lacking toxicity data, more contemporary and high-throughput approaches such as read-across, molecular dynamics, and protein modeling are proposed to accelerate the development of toxicity information on emerging and legacy PFAS, individually and as mixtures. In addition, an appropriate degree of precaution, given what is already known from the PFAS examples noted, may be needed to protect human health.
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              PFAS Exposure Pathways for Humans and Wildlife: A Synthesis of Current Knowledge and Key Gaps in Understanding

              We synthesize current understanding of the magnitudes and methods for assessing human and wildlife exposures to poly- and perfluoroalkyl substances (PFAS). Most human exposure assessments have focused on 2 to 5 legacy PFAS, and wildlife assessments are typically limited to targeted PFAS (up to ~30 substances). However, shifts in chemical production are occurring rapidly, and targeted methods for detecting PFAS have not kept pace with these changes. Total fluorine measurements complemented by suspect screening using high-resolution mass spectrometry are thus emerging as essential tools for PFAS exposure assessment. Such methods enable researchers to better understand contributions from precursor compounds that degrade into terminal perfluoroalkyl acids. Available data suggest that diet is the major human exposure pathway for some PFAS, but there is large variability across populations and PFAS compounds. Additional data on total fluorine in exposure media and the fraction of unidentified organofluorine are needed. Drinking water has been established as the major exposure source in contaminated communities. As water supplies are remediated, for the general population, exposures from dust, personal care products, indoor environments, and other sources may be more important. A major challenge for exposure assessments is the lack of statistically representative population surveys. For wildlife, bioaccumulation processes differ substantially between PFAS and neutral lipophilic organic compounds, prompting a reevaluation of traditional bioaccumulation metrics. There is evidence that both phospholipids and proteins are important for the tissue partitioning and accumulation of PFAS. New mechanistic models for PFAS bioaccumulation are being developed that will assist in wildlife risk evaluations. Environ Toxicol Chem 2021;40:631-657. © 2020 SETAC.
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                Author and article information

                Journal
                8308958
                8619
                Environ Toxicol Chem
                Environ Toxicol Chem
                Environmental toxicology and chemistry
                0730-7268
                1552-8618
                22 May 2024
                January 2024
                29 November 2023
                01 January 2025
                : 43
                : 1
                : 115-131
                Affiliations
                [a ]Environmental Laboratory, Engineer Research and Development Center, US Army, Vicksburg, Mississippi, USA
                [b ]Bennett Aerospace, Cary, North Carolina, USA
                [c ]Oak Ridge Institute for Science and Education, Oak Ridge, Tennessee, USA
                [d ]Great Lakes Toxicology and Ecology Division, US Environmental Protection Agency, Duluth, Minnesota, USA
                [e ]Geosyntec Consultants, Costa Mesa, California, USA
                Author notes

                Author Contribution StatementKurt A. Gust: Conceptualization; Data curation; Formal analysis; Funding acquisition; Investigation; Methodology; Project administration; Supervision; Validation; Visualization; Writing—original draft; Writing—review & editing. J. Erik Mylroie: Conceptualization; Data curation; Formal analysis; Investigation; Methodology; Project administration; Supervision; Visualization; Writing—original draft; Writing—review & editing. Ashley N. Kimble: Data curation; Formal analysis; Investigation; Methodology; Writing—original draft; Writing—review & editing. Mitchell S. Wilbanks: Data curation; Formal analysis; Investigation; Methodology; Project administration; Writing—review & editing. Catherine S. C. Steward: Investigation; Methodology; Writing—review & editing. Kacy A. Chapman: Investigation; Methodology. Kathleen M. Jensen: Formal analysis; Investigation; Methodology; Writing—original draft. Alan J. Kennedy: Formal Analysis; Writing—original draft; Writing—review & editing. Paige M. Krupa: Writing—review & editing. Scott A. Waisner: Methodology. Zacharias Pandelides: Formal analysis; Investigation; Writing—review & editing. Natalia Garcia-Reyero: Conceptualization; Funding acquisition; Methodology; Project administration; Supervision; Writing—review & editing. Russell J. Erickson: Conceptualization; Formal analysis; Investigation; Methodology; Validation; Writing—original draft; Writing—review & editing. Gerald T. Ankley: Conceptualization; Investigation; Validation; Writing—review & editing. Jason Conder: Conceptualization; Formal analysis; Investigation; Validation; Writing—review & editing. David W. Moore: Conceptualization; Funding acquisition; Investigation; Project administration; Supervision; Validation; Writing—original draft; Writing—review & editing.

                [* ]Address correspondence to kurt.a.gust@ 123456usace.army.mil
                Article
                EPAPA1990584
                10.1002/etc.5770
                11131580
                38018867
                f9601cc1-3f9c-4387-b0f9-7d39b18a2203

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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                Categories
                Article

                Environmental chemistry
                zebrafish,perfluorooctane sulfonic acid (pfos),multigenerational exposure,growth,reproduction

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