Starnes Hannah M, Rock Kylie D, Jackson Thomas W, Belcher Scott M
Center for Environmental and Health Effects of PFAS, Department of Biological Sciences, North Carolina State University, Raleigh, NC, United States.
Front Toxicol. 2022 Apr 11;4:881584. doi: 10.3389/ftox.2022.881584. eCollection 2022.
Per- and polyfluoroalkyl substances (PFAS) are a class of structurally diverse synthetic organic chemicals that are chemically stable, resistant to degradation, and persistent in terrestrial and aquatic environments. Widespread use of PFAS in industrial processing and manufacturing over the last 70 years has led to global contamination of built and natural environments. The brain is a lipid rich and highly vascularized organ composed of long-lived neurons and glial cells that are especially vulnerable to the impacts of persistent and lipophilic toxicants. Generally, PFAS partition to protein-rich tissues of the body, primarily the liver and blood, but are also detected in the brains of humans, wildlife, and laboratory animals. Here we review factors impacting the absorption, distribution, and accumulation of PFAS in the brain, and currently available evidence for neurotoxic impacts defined by disruption of neurochemical, neurophysiological, and behavioral endpoints. Emphasis is placed on the neurotoxic potential of exposures during critical periods of development and in sensitive populations, and factors that may exacerbate neurotoxicity of PFAS. While limitations and inconsistencies across studies exist, the available body of evidence suggests that the neurobehavioral impacts of long-chain PFAS exposures during development are more pronounced than impacts resulting from exposure during adulthood. There is a paucity of experimental studies evaluating neurobehavioral and molecular mechanisms of short-chain PFAS, and even greater data gaps in the analysis of neurotoxicity for PFAS outside of the perfluoroalkyl acids. Whereas most experimental studies were focused on acute and subchronic impacts resulting from high dose exposures to a single PFAS congener, more realistic exposures for humans and wildlife are mixtures exposures that are relatively chronic and low dose in nature. Our evaluation of the available human epidemiological, experimental, and wildlife data also indicates heightened accumulation of perfluoroalkyl acids in the brain after environmental exposure, in comparison to the experimental studies. These findings highlight the need for additional experimental analysis of neurodevelopmental impacts of environmentally relevant concentrations and complex mixtures of PFAS.
全氟和多氟烷基物质（PFAS）是一类结构多样的合成有机化学品，它们化学性质稳定，抗降解，并且在陆地和水生环境中持久存在。在过去70年中，PFAS在工业加工和制造中的广泛使用导致了建筑环境和自然环境的全球污染。大脑是一个富含脂质且血管高度丰富的器官，由长寿的神经元和神经胶质细胞组成，这些细胞特别容易受到持久性和亲脂性毒物的影响。一般来说，PFAS会分布到人体富含蛋白质的组织中，主要是肝脏和血液，但在人类、野生动物和实验动物的大脑中也能检测到。在这里，我们回顾了影响PFAS在大脑中吸收、分布和积累的因素，以及目前关于神经化学、神经生理学和行为终点破坏所定义的神经毒性影响的现有证据。重点关注发育关键期和敏感人群暴露期间的神经毒性潜力，以及可能加剧PFAS神经毒性的因素。虽然各研究存在局限性和不一致性，但现有证据表明，发育期间长期接触长链PFAS对神经行为的影响比成年期接触产生的影响更为明显。评估短链PFAS神经行为和分子机制的实验研究很少，对于全氟烷基酸以外的PFAS的神经毒性分析数据差距更大。虽然大多数实验研究集中在高剂量接触单一PFAS同系物所产生的急性和亚慢性影响上，但对人类和野生动物来说，更现实的接触是相对慢性和低剂量的混合接触。我们对现有人类流行病学、实验和野生动物数据的评估还表明，与实验研究相比，环境暴露后大脑中全氟烷基酸的积累增加。这些发现凸显了对环境相关浓度和PFAS复杂混合物的神经发育影响进行额外实验分析的必要性。
