Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, 1089 VM3B, Davis, CA, 95616, USA.
Professor Emeritus, School of Public Health, University at Albany, Rensselaer, NY, USA.
Acta Neuropathol. 2019 Sep;138(3):363-387. doi: 10.1007/s00401-019-01978-1. Epub 2019 Apr 11.
Halogenated organic compounds are pervasive in natural and built environments. Despite restrictions on the production of many of these compounds in most parts of the world through the Stockholm Convention on Persistent Organic Pollutants (POPs), many "legacy" compounds, including polychlorinated biphenyls (PCBs), are routinely detected in human tissues where they continue to pose significant health risks to highly exposed and susceptible populations. A major concern is developmental neurotoxicity, although impacts on neurodegenerative outcomes have also been noted. Here, we review human studies of prenatal and adult exposures to PCBs and describe the state of knowledge regarding outcomes across domains related to cognition (e.g., IQ, language, memory, learning), attention, behavioral regulation and executive function, and social behavior, including traits related to attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASD). We also review current understanding of molecular mechanisms underpinning these associations, with a focus on dopaminergic neurotransmission, thyroid hormone disruption, calcium dyshomeostasis, and oxidative stress. Finally, we briefly consider contemporary sources of organohalogens that may pose human health risks via mechanisms of neurotoxicity common to those ascribed to PCBs.
卤代有机化合物广泛存在于自然和人工环境中。尽管《斯德哥尔摩持久性有机污染物公约》（POPs）限制了世界大部分地区许多此类化合物的生产，但许多“遗留”化合物，包括多氯联苯（PCBs），仍在人体组织中经常被检测到，这些化合物继续对高度暴露和易感人群构成重大健康风险。一个主要关注点是发育神经毒性，尽管也注意到了对神经退行性疾病结果的影响。在这里，我们回顾了人类对产前和成人接触多氯联苯的研究，并描述了与认知（例如，智商、语言、记忆、学习）、注意力、行为调节和执行功能以及社会行为相关领域的知识状况，包括与注意力缺陷多动障碍（ADHD）和自闭症谱系障碍（ASD）相关的特征。我们还回顾了当前对这些关联背后的分子机制的理解，重点是多巴胺能神经传递、甲状腺激素紊乱、钙动态平衡紊乱和氧化应激。最后，我们简要考虑了可能通过与多氯联苯归因的神经毒性机制对人类健康构成风险的当代有机卤代物来源。
