National Toxicology Program Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
West Virginia University School of Public Health, Morgantown, West Virginia, USA.
Environ Toxicol Chem. 2021 Mar;40(3):606-630. doi: 10.1002/etc.4890. Epub 2020 Dec 7.
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. Environ Toxicol Chem 2021;40:606-630. © 2020 SETAC.
有关环境和人类健康受全氟和多氟烷基物质（PFAS）影响的报告在同行评议文献中大量增加。本综述的目的是评估关于 PFAS 毒理学效应的科学现状，并制定策略来增进对这一大类化学物质健康影响的认识。目前，可用于 PFAS 的毒性数据主要来自少数几种化学物质，主要是全氟辛酸和全氟辛烷磺酸等传统 PFAS。流行病学研究表明，接触特定 PFAS 与多种健康影响之间存在关联，包括免疫和甲状腺功能改变、肝病、脂质和胰岛素失调、肾病、不良生殖和发育结果以及癌症。这些影响中的许多都与实验动物数据一致。然而，必须扩展作用模式和不良结果途径的信息，并考虑 PFAS 毒代动力学特性的巨大差异，以了解性别之间以及物种和生命阶段之间反应的差异。由于为数相对较少的几种示例化合物注意到许多健康影响，而商业中其他数百种 PFAS 缺乏毒性数据，因此提议采用更现代和高通量的方法，如外推、分子动力学和蛋白质建模，以加速新兴和传统 PFAS 的毒性信息的开发，包括单独和作为混合物。此外，鉴于已经从上述 PFAS 示例中了解到的情况，可能需要采取适当程度的预防措施来保护人类健康。环境毒理化学 2021；40:606-630。版权所有 2020 SETAC。
