Abstract

Background:

Thousands of per- and polyfluoroalkyl substances (PFAS) with diverse structures have been detected in the ambient environment. Apart from a few well-studied PFAS, the structure-related toxicokinetics of a broader set of PFAS remain unclear.

Objectives:

To understand the toxicokinetics of PFAS, we attempted to characterize the metabolism pathways of 74 structurally diverse PFAS samples from the U.S. Environmental Protection Agency’s PFAS screening library.

Methods:

Using the early life stages of zebrafish (Danio rerio) as a model, we determined the bioconcentration factors and phenotypic toxicities of 74 PFAS. Then, we applied high-resolution mass spectrometry–based nontargeted analysis to identify metabolites of PFAS in zebrafish larvae after 5 d of exposure by incorporating retention time and mass spectra. In vitro enzymatic activity experiments with human recombinant liver carboxylesterase (hCES1) were employed to validate the structure-related hydrolysis of 11 selected PFAS.

Results:

Our findings identified five structural categories of PFAS prone to metabolism. The metabolism pathways of PFAS were highly related to their structures as exemplified by fluorotelomer alcohols that the predominance of $\mathrm{\beta }\text{-oxidation}$ or taurine conjugation pathways were primarily determined by the number of hydrocarbons. Hydrolysis was identified as a major metabolism pathway for diverse PFAS, and perfluoroalkyl carboxamides showed the highest in vivo hydrolysis rates, followed by carboxyesters and sulfonamides. The hydrolysis of PFAS was verified with recombinant hCES1, with strong substrate preferences toward perfluoroalkyl carboxamides.

Conclusions:

We suggest that the roadmap of the structure-related metabolism pathways of PFAS established in this study would provide a starting point to inform the potential health risks of other PFAS. https://doi.org/10.1289/EHP7169

中文翻译：

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斑马鱼生命早期全氟和多氟烷基物质的结构相关代谢途径路线图（斑马鱼）

摘要

背景：

在周围环境中已检测到数千种具有不同结构的全氟烷基和多氟烷基物质 (PFAS)。除了一些经过充分研究的 PFAS 之外，更广泛的 PFAS 的结构相关毒代动力学仍不清楚。

目标：

为了了解 PFAS 的毒代动力学，我们试图描述来自美国环境保护署 PFAS 筛选库的 74 个结构不同的 PFAS 样品的代谢途径。

方法：

我们以斑马鱼 ( Danio rerio )的早期生命阶段为模型，确定了 74 种 PFAS 的生物浓缩因子和表型毒性。然后，我们应用基于高分辨率质谱的非靶向分析，通过结合保留时间和质谱，在斑马鱼幼虫暴露 5 天后鉴定 PFAS 的代谢物。采用人重组肝羧酸酯酶 ( h CES1) 的体外酶活性实验验证了 11 种选定 PFAS 的结构相关水解。

结果：

我们的研究结果确定了五种易于代谢的 PFAS 结构类别。PFAS 的代谢途径与其结构高度相关，以氟调聚物醇为例，$\mathrm{\beta }\text{-氧化}$或牛磺酸共轭途径主要由碳氢化合物的数量决定。水解被确定为多种 PFAS 的主要代谢途径，全氟烷基甲酰胺在体内的水解率最高，其次是羧酸酯和磺胺。PFAS 的水解用重组h CES1 验证，对全氟烷基甲酰胺具有强烈的底物偏好。

结论：

我们建议，本研究中建立的 PFAS 结构相关代谢途径的路线图将为了解其他 PFAS 的潜在健康风险提供一个起点。https://doi.org/10.1289/EHP7169