N-glucuronidation and Excretion of Perfluoroalkyl Sulfonamides in Mice Following Ingestion of Aqueous Film-Forming Foam

IF 3.6 4区环境科学与生态学 Q2 ENVIRONMENTAL SCIENCES Environmental Toxicology and Chemistry Pub Date : 2024-06-24 DOI:10.1002/etc.5939

David A. Dukes, Carrie A. McDonough

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Abstract

Perfluoroalkyl sulfonamides (FASAs) and other FASA-based per- and polyfluoroalkyl substances (PFASs) can transform into recalcitrant perfluoroalkyl sulfonates in vivo. We conducted high-resolution mass spectrometry suspect screening of urine and tissues (kidney and liver) from mice dosed with an electrochemically fluorinated aqueous film-forming foam (AFFF) to better understand the biological fate of AFFF-associated precursors. The B6C3F1 mice were dosed at five levels (0, 0.05, 0.5, 1, and 5 mg kg⁻¹ day⁻¹) based on perfluorooctane sulfonate and perfluorooctanoate content of the AFFF mixture. Dosing continued for 10 days followed by a 6-day depuration. Total oxidizable precursor assay of the AFFF suggested significant contributions from precursors with three to six perfluorinated carbons. We identified C4 to C6 FASAs and N-glucuronidated FASAs (FASA-N-glus) excreted in urine collected throughout dosing and depuration. Based on normalized relative abundance, FASA-N-glus accounted for up to 33% of the total excreted FASAs in mouse urine, highlighting the importance of phase II metabolic conjugation as a route of excretion. High-resolution mass spectrometry screening of liver and kidney tissue revealed accumulation of longer-chain (C7 and C8) FASAs not detected in urine. Chain-length–dependent conjugation of FASAs was also observed by incubating FASAs with mouse liver S9 fractions. Shorter-chain (C4) FASAs conjugated to a much greater extent over a 120-min incubation than longer-chain (C8) FASAs. Overall, this study highlights the significance of N-glucuronidation as an excretion mechanism for short-chain FASAs and suggests that monitoring urine for FASA-N-glus could contribute to a better understanding of PFAS exposure, as FASAs and their conjugates are often overlooked by traditional biomonitoring studies. Environ Toxicol Chem 2024;43:2274–2284. © 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

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小鼠摄入水成膜泡沫后体内全氟烷基磺酰胺的 N-葡萄糖醛酸化和排泄。

全氟烷基磺酰胺（FASA）和其他以 FASA 为基础的全氟和多氟烷基物质（PFASs）可在体内转化为难降解的全氟烷基磺酸盐。我们对服用了电化学含氟水成膜泡沫（AFFF）的小鼠的尿液和组织（肾脏和肝脏）进行了高分辨率质谱疑似筛选，以更好地了解 AFFF 相关前体的生物学归宿。根据 AFFF 混合物中全氟辛烷磺酸和全氟辛酸的含量，对 B6C3F1 小鼠进行了五次剂量试验（0、0.05、0.5、1 和 5 毫克/公斤-1 天-1）。投药持续 10 天，然后进行为期 6 天的停药。全氟烯烃的总可氧化前体分析表明，含有三至六个全氟碳原子的前体对全氟烯烃有重大影响。我们在整个用药和停药期间收集的尿液中发现了排泄的 C4 至 C6 FASAs 和 N-葡萄糖醛酸化 FASAs（FASA-N-glus）。根据归一化的相对丰度，FASA-N-glus 占小鼠尿液中排泄的 FASAs 总量的 33%，这突出了 II 期代谢共轭作为排泄途径的重要性。肝脏和肾脏组织的高分辨率质谱筛选显示，尿液中未检测到长链（C7 和 C8）FASAs 的积累。通过将 FASAs 与小鼠肝脏 S9 分馏物孵育，还观察到 FASAs 的链长依赖性共轭作用。与长链（C8）FASAs 相比，短链（C4）FASAs 在 120 分钟孵育过程中的共轭程度更高。总之，这项研究强调了N-葡萄糖醛酸化作为短链FASA排泄机制的重要性，并表明监测尿液中的FASA-N-葡萄糖有助于更好地了解PFAS的暴露情况，因为传统的生物监测研究往往忽略了FASA及其共轭物。环境毒物化学 2024;00:1-11。© 2024 The Author(s).环境毒理学与化学》由 Wiley Periodicals LLC 代表 SETAC 出版。

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来源期刊

Environmental Toxicology and Chemistry 环境科学-毒理学

CiteScore

7.40

自引率

9.80%

发文量

265

审稿时长

3.4 months

期刊介绍： The Society of Environmental Toxicology and Chemistry (SETAC) publishes two journals: Environmental Toxicology and Chemistry (ET&C) and Integrated Environmental Assessment and Management (IEAM). Environmental Toxicology and Chemistry is dedicated to furthering scientific knowledge and disseminating information on environmental toxicology and chemistry, including the application of these sciences to risk assessment.[...] Environmental Toxicology and Chemistry is interdisciplinary in scope and integrates the fields of environmental toxicology; environmental, analytical, and molecular chemistry; ecology; physiology; biochemistry; microbiology; genetics; genomics; environmental engineering; chemical, environmental, and biological modeling; epidemiology; and earth sciences. ET&C seeks to publish papers describing original experimental or theoretical work that significantly advances understanding in the area of environmental toxicology, environmental chemistry and hazard/risk assessment. Emphasis is given to papers that enhance capabilities for the prediction, measurement, and assessment of the fate and effects of chemicals in the environment, rather than simply providing additional data. The scientific impact of papers is judged in terms of the breadth and depth of the findings and the expected influence on existing or future scientific practice. Methodological papers must make clear not only how the work differs from existing practice, but the significance of these differences to the field. Site-based research or monitoring must have regional or global implications beyond the particular site, such as evaluating processes, mechanisms, or theory under a natural environmental setting.

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