Abstract
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.
Highlights
Polychlorinated biphenyls (PCBs) are a structurally related class of 209 organochlorine compounds, individually referred to as congeners
In 1979, prompted by evidence of their environmental persistence and growing concerns regarding human cancer risks, the United States banned commercial production of PCBs. This was followed by a global ban on PCB production instituted by signatory nations during the Stockholm Convention on Persistent Organic Pollutants (POPs) in 2001, which was appended in 2008 and 2014 [2,3]. These regulatory efforts resulted in the steady decline of environmental levels of legacy indicator PCBs
Humans continue to be exposed to legacy PCBs because of their continued release from hazardous waste sites, PCB-containing equipment still in use, and construction materials used in buildings erected prior to the ban on PCB production [4,5,6]
Summary
Polychlorinated biphenyls (PCBs) are a structurally related class of 209 organochlorine compounds, individually referred to as congeners. Data emerging over the past decade demonstrates widespread human exposure to non-legacy PCB congeners that were not present in the commercial PCB mixtures [8] These non-legacy PCBs are detected in indoor and outdoor environments and in human tissues and the most likely source of these contaminants is off gassing from common household paints [9,10]. In contrast to the commercially produced PCBs, levels of the non-legacy PCBs are increasing in the environment and in human tissues [7,11] Both human and animal studies identify the developing brain as a vulnerable target of PCBs. Multiple reviews of the epidemiologic literature have concluded that exposure to PCBs during critical developmental periods increases the risks of neuropsychological deficits in children, demonstrated by impaired executive and psychomotor function, as well as deficits in attention, learning, and memory [14,15,16,17]. This review focuses on recent research that is beginning to shed light on these questions
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