The developmental neurotoxicity of legacy vs. contemporary polychlorinated biphenyls (PCBs): similarities and differences
Although banned from production for decades, PCBs remain a significant risk to human health. A primary target of concern is the developing brain. Epidemiological studies link PCB exposures in utero or during infancy to increased risk of neuropsychiatric deficits in children. Nonclinical studies of legacy congeners found in PCB mixtures synthesized prior to the ban on PCB production suggest that non-dioxin-like (NDL) congeners are predominantly responsible for the developmental neurotoxicity associated with PCB exposures. Mechanistic studies suggest that NDL PCBs alter neurodevelopment via ryanodine receptor-dependent effects on dendritic arborization. Lightly chlorinated congeners, which were not present in the industrial mixtures synthesized prior to the ban on PCB production, have emerged as contemporary environmental contaminants, but there is a paucity of data regarding their potential developmental neurotoxicity. PCB 11, a prevalent contemporary congener, is found in the serum of children and their mothers, as well as in the serum of pregnant women at increased risk for having a child diagnosed with a neurodevelopmental disorder (NDD). Recent data demonstrates that PCB 11 modulates neuronal morphogenesis via mechanisms that are convergent with and divergent from those implicated in the developmental neurotoxicity of legacy NDL PCBs. This review summarizes these data and discusses their relevance to adverse neurodevelopmental outcomes in humans.
KeywordsAxonal outgrowth Calcium signaling CREB Dendritic arborization Neuronal morphogenesis Neurodevelopmental disorders Persistent organic pollutants Ryanodine receptor
This work was supported by the United States National Institute of Environmental Health (grant numbers R01 ES014901, R01 ES014901-09S1 (ViCTER supplement), P30 ES023513, T32 ES007059).
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Conflict of interest
The authors have no conflicts of interest to disclose.
The sponsors were not involved in the writing of the paper or in the decision to submit the work for publication.
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