Liu Sheng, Dukes David A, Koelmel Jeremy P, Stelben Paul, Finch Jasen, Okeme Joseph, Lowe Charles, Williams Antony, Godri David, Rennie Emma E, Parry Emily, McDonough Carrie A, Godri Pollitt Krystal J
Department of Environmental Health Science, Yale School of Public Health, New Haven, Connecticut 06511, United States.
Department of Civil Engineering, Stony Brook University, Stony Brook, New York 11794, United States.
Environ Sci Technol. 2025 Jan 14;59(1):119-131. doi: 10.1021/acs.est.4c07750. Epub 2024 Dec 20.
Per- and polyfluoroalkyl substances (PFAS) are widely used persistent synthetic chemicals that have been linked to adverse health effects. While the behavior of PFAS has been evaluated in the environment, our understanding of reaction products in mammalian systems is limited. This study identified biological PFAS transformation products and generated mass spectral libraries to facilitate an automated search and identification. The biological transformation products of 27 PFAS, spanning 5 chemical subclasses (alcohols, sulfonamides, carboxylic acids, ethers, and esters), were evaluated following enzymatic reaction with mouse liver S9 fractions. Four major pathways were identified by liquid chromatography-high-resolution mass spectrometry: glucuronidation, sulfation, dealkylation, and oxidation. Class-based fragmentation rules and associated PFAS transformation product libraries were generated and integrated into an automated nontargeted PFAS data analysis software (FluoroMatch). Fragmentation was additionally predicted for the potential transformation products of more than 2,500 PFAS in the EPA CompTox Chemicals Dashboard PFASSTRUCTv4. Generated mass spectral libraries were validated by applying FluoroMatch to a data set of urine from aqueous film-forming foam (AFFF)-dosed mice. Toxicity predictions showed identified PFAS transformation products to be potential developmental and mutagenic toxicants. This research enables more comprehensive PFAS characterization in biological systems, which will improve the assessment of exposures and evaluation of the associated health impacts.
全氟和多氟烷基物质（PFAS）是广泛使用的持久性合成化学品，已被证明与不良健康影响有关。虽然PFAS在环境中的行为已得到评估，但我们对其在哺乳动物系统中的反应产物的了解仍然有限。本研究鉴定了生物PFAS转化产物，并生成了质谱库，以促进自动搜索和鉴定。在与小鼠肝脏S9组分进行酶促反应后，评估了27种PFAS的生物转化产物，这些PFAS涵盖5个化学亚类（醇类、磺酰胺类、羧酸类、醚类和酯类）。通过液相色谱-高分辨率质谱法确定了四条主要途径：葡萄糖醛酸化、硫酸化、脱烷基化和氧化。基于类别的裂解规则和相关的PFAS转化产物库被生成，并整合到一个自动化的非靶向PFAS数据分析软件（FluoroMatch）中。此外，还对美国环境保护局（EPA）综合毒性化学品仪表板PFASSTRUCTv4中2500多种PFAS的潜在转化产物进行了裂解预测。通过将FluoroMatch应用于来自水成膜泡沫（AFFF）给药小鼠的尿液数据集，对生成的质谱库进行了验证。毒性预测表明，已鉴定的PFAS转化产物是潜在的发育和致突变毒物。这项研究能够在生物系统中对PFAS进行更全面的表征，这将改善对暴露的评估以及对相关健康影响的评价。
