Department of Molecular Biosciences, University of California, Davis, School of Veterinary Medicine, Davis, CA 95616, USA.
Int J Mol Sci. 2020 Feb 4;21(3):1013. doi: 10.3390/ijms21031013.
Despite being banned from production for decades, polychlorinated biphenyls (PCBs) continue to pose a significant risk to human health. This is due to not only the continued release of legacy PCBs from PCB-containing equipment and materials manufactured prior to the ban on PCB production, but also the inadvertent production of PCBs as byproducts of contemporary pigment and dye production. Evidence from human and animal studies clearly identifies developmental neurotoxicity as a primary endpoint of concern associated with PCB exposures. However, the relative role(s) of specific PCB congeners in mediating the adverse effects of PCBs on the developing nervous system, and the mechanism(s) by which PCBs disrupt typical neurodevelopment remain outstanding questions. New questions are also emerging regarding the potential developmental neurotoxicity of lower chlorinated PCBs that were not present in the legacy commercial PCB mixtures, but constitute a significant proportion of contemporary human PCB exposures. Here, we review behavioral and mechanistic data obtained from experimental models as well as recent epidemiological studies that suggest the non-dioxin-like (NDL) PCBs are primarily responsible for the developmental neurotoxicity associated with PCBs. We also discuss emerging data demonstrating the potential for non-legacy, lower chlorinated PCBs to cause adverse neurodevelopmental outcomes. Molecular targets, the relevance of PCB interactions with these targets to neurodevelopmental disorders, and critical data gaps are addressed as well.
尽管多氯联苯 (PCBs) 已被禁止生产数十年，但它们仍对人类健康构成重大风险。这不仅是因为在禁止生产 PCB 之前生产的含有 PCB 的设备和材料中持续释放旧 PCB，还因为在当代颜料和染料生产中无意产生了 PCB 作为副产品。人类和动物研究的证据清楚地表明，发育神经毒性是与 PCB 暴露相关的主要关注终点。然而，特定 PCB 同系物在介导 PCB 对发育中神经系统的不良影响中的相对作用，以及 PCB 破坏典型神经发育的机制，仍然是悬而未决的问题。新的问题也出现在低氯代 PCB 上，这些 PCB 不存在于遗留的商业 PCB 混合物中，但构成了当代人类 PCB 暴露的重要部分，它们是否具有潜在的发育神经毒性。在这里，我们回顾了来自实验模型和最近的流行病学研究的行为和机制数据，这些数据表明，非二恶英类（NDL）PCBs 是与 PCB 相关的发育神经毒性的主要原因。我们还讨论了新出现的数据，这些数据表明非遗留的、低氯代 PCB 可能导致不良的神经发育结果。分子靶点、PCB 与这些靶点相互作用对神经发育障碍的相关性以及关键数据差距也得到了探讨。
