Abstract

Background:

Per- and polyfluoroalkyl substances (PFAS) are a large class of synthetic (man-made) chemicals widely used in consumer products and industrial processes. Thousands of distinct PFAS exist in commerce. The 2019 U.S. Environmental Protection Agency (U.S. EPA) Per- and Polyfluoroalkyl Substances (PFAS) Action Plan outlines a multiprogram national research plan to address the challenge of PFAS. One component of this strategy involves the use of systematic evidence map (SEM) approaches to characterize the evidence base for hundreds of PFAS.

Objective:

SEM methods were used to summarize available epidemiological and animal bioassay evidence for a set of $\sim 150$ PFAS that were prioritized in 2019 by the U.S. EPA’s Center for Computational Toxicology and Exposure (CCTE) for in vitro toxicity and toxicokinetic assay testing.

Methods:

Systematic review methods were used to identify and screen literature using manual review and machine-learning software. The Populations, Exposures, Comparators, and Outcomes (PECO) criteria were kept broad to identify mammalian animal bioassay and epidemiological studies that could inform human hazard identification. A variety of supplemental content was also tracked, including information on in vitro model systems; exposure measurement–only studies in humans; and absorption, distribution, metabolism, and excretion (ADME). Animal bioassay and epidemiology studies meeting PECO criteria were summarized with respect to study design, and health system(s) were assessed. Because animal bioassay studies with $\ge 21\text{-d}$ exposure duration (or reproductive/developmental study design) were most useful to CCTE analyses, these studies underwent study evaluation and detailed data extraction. All data extraction is publicly available online as interactive visuals with downloadable metadata.

Results:

More than 40,000 studies were identified from scientific databases. Screening processes identified 44 animal and 148 epidemiology studies from the peer-reviewed literature and 95 animal and 50 epidemiology studies from gray literature that met PECO criteria. Epidemiological evidence (available for 15 PFAS) mostly assessed the reproductive, endocrine, developmental, metabolic, cardiovascular, and immune systems. Animal evidence (available for 40 PFAS) commonly assessed effects in the reproductive, developmental, urinary, immunological, and hepatic systems. Overall, 45 PFAS had evidence across animal and epidemiology data streams.

Discussion:

Many of the $\sim 150$ PFAS were data poor. Epidemiological and animal evidence were lacking for most of the PFAS included in our search. By disseminating this information, we hope to facilitate additional assessment work by providing the initial scoping literature survey and identifying key research needs. Future research on data-poor PFAS will help support a more complete understanding of the potential health effects from PFAS exposures. https://doi.org/10.1289/EHP10343

中文翻译：

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超过一百五十种全氟烷基物质和多氟烷基物质 (PFAS) 的系统证据图

 抽象的

 背景：

全氟烷基物质和多氟烷基物质 (PFAS) 是一大类合成（人造）化学品，广泛用于消费品和工业过程。商业中存在数以千计的不同 PFAS。 2019 年美国环境保护署 (US EPA) 全氟烷基物质和多氟烷基物质 (PFAS) 行动计划概述了一项旨在应对 PFAS 挑战的多项目国家研究计划。该策略的一个组成部分涉及使用系统证据图 (SEM) 方法来描述数百种 PFAS 的证据基础。

 客观的：

使用 SEM 方法总结了一组可用的流行病学和动物生物测定证据$<span\; data-immersive-translate-walked="a80e61c0-a938-4f1a-9e04-5d0e90b58de3">～</span>\mathrm{<span\; data-immersive-translate-walked="a80e61c0-a938-4f1a-9e04-5d0e90b58de3">150</span>}$ 2019 年，美国 EPA 计算毒理学和暴露中心 (CCTE) 优先对 PFAS 进行体外毒性和毒代动力学测定测试。

 方法：

采用系统评审方法，利用人工评审和机器学习软件来识别和筛选文献。人群、暴露、比较和结果 (PECO) 标准保持广泛，以确定可以为人类危害识别提供信息的哺乳动物生物测定和流行病学研究。还跟踪了各种补充内容，包括体外模型系统的信息；暴露测量——仅针对人类的研究；吸收、分布、代谢和排泄 (ADME)。总结了符合 PECO 标准的动物生物测定和流行病学研究的研究设计，并对卫生系统进行了评估。因为动物生物测定研究$<span\; data-immersive-translate-walked="a80e61c0-a938-4f1a-9e04-5d0e90b58de3">\ge </span>\mathrm{<span\; data-immersive-translate-walked="a80e61c0-a938-4f1a-9e04-5d0e90b58de3">21</span>}\text{<span data-immersive-translate-walked="a80e61c0-a938-4f1a-9e04-5d0e90b58de3">-d</span>}$暴露持续时间（或生殖/发育研究设计）对 CCTE 分析最有用，这些研究进行了研究评估和详细数据提取。所有数据提取均以交互式视觉效果和可下载元数据的形式在线公开提供。

 结果：

从科学数据库中发现了超过 40,000 项研究。筛选过程从同行评审文献中确定了 44 项动物研究和 148 项流行病学研究，从灰色文献中确定了 95 项动物研究和 50 项流行病学研究，符合 PECO 标准。流行病学证据（适用于 15 种 PFAS）主要评估生殖、内分泌、发育、代谢、心血管和免疫系统。动物证据（适用于 40 种 PFAS）通常评估对生殖、发育、泌尿、免疫和肝脏系统的影响。总体而言，45 种 PFAS 具有跨动物和流行病学数据流的证据。

 讨论：

许多$<span\; data-immersive-translate-walked="a80e61c0-a938-4f1a-9e04-5d0e90b58de3">～</span>\mathrm{<span\; data-immersive-translate-walked="a80e61c0-a938-4f1a-9e04-5d0e90b58de3">150</span>}$ PFAS 数据贫乏。我们搜索中的大多数 PFAS 缺乏流行病学和动物证据。通过传播这些信息，我们希望通过提供初步范围文献调查和确定关键研究需求来促进额外的评估工作。未来对缺乏数据的 PFAS 的研究将有助于更全面地了解 PFAS 暴露对健康的潜在影响。 https://doi.org/10.1289/EHP10343