A handbook of environmental toxicology: human disorders and ecotoxicology.

Chapter 11 (Page no: 156)

The developmental neurotoxicity of polychlorinated biphenyls: a continuing environmental health concern.

Polychlorinated biphenyls (PCBs) are synthetic chemicals widely used in diverse industrial applications and commercial products until their production was banned in the 1970s due to concerns regarding their environmental persistence and human health risks. Despite the ban, environmental levels of PCBs have not declined significantly over the past two decades, and more recently, contemporary PCBs not synthesized in the original industrial mixtures have been identified as inadvertent by-products of modern pigment manufacturing processes. PCBs remain contaminants of considerable concern because of their demonstrated adverse effects on neurodevelopment in human and animal models. This chapter briefly summarizes human literature and animal data documenting the developmental neurotoxicity (DNT) of PCBs and then focuses on the mechanisms by which PCBs are postulated to interfere with neurodevelopment, a question that remains a subject of much debate. The predominant mechanistic hypotheses of PCB DNT include disruption of thyroid hormone signalling, altered neurotransmitter signalling, perturbation of calcium homeostasis and the induction of oxidative stress. Of these, calcium signalling is the most sensitive and experimental data support a causal link between PCB effects on calcium signalling and the perturbation of critical neurodevelopmental processes, specifically dendritic arborization and apoptosis. Nonetheless, it cannot be ruled out that more than one mechanism contributes to PCB DNT, and it seems likely that the various molecular effects of PCBs may be interrelated. This chapter also identifies key data gaps regarding PCB DNT and describes strategies for addressing these gaps to develop a better understanding of the threat PCBs pose to the developing brain.

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