NEUROCHEMICAL EFFECTS OF POLYCHLORINATED-BIPHENYLS - AN OVERVIEW AND IDENTIFICATION OF RESEARCH NEEDS

The PCBs are members of the halogenated hydrocarbon class of environme ntal chemicals that includes the dibenzofurans and dioxins. The PCBs w ere used over a period of 40 years for number of industrial purposes. Their appearance in the ecosystem and biological samples from wildlife , as well as documented cases of accidental poisoning led to the banni ng of their manufacture in 1977. The PCBs continue to be of concern to environmental toxicologists because of their persistence in the envir onment and reports that exposure to relatively low levels may be assoc iated with subtle behavioral and neurological deficits, particularly i i exposure occurs during development. Developmental neurotoxicity of P CBs has been reported in humans and confirmed in several laboratory an imal species, including non-human primates. During the last 20 years, there has been an attempt to understand the cellular bases of PCB-indu ced behavioral and neurological effects in animal models. Exposure of adult animals to a single, relatively high dose of PCBs decreases the content of several brain neurotransmitters, while repeated exposure to lower PCB doses appears to affect brain DA metabolism. The mechanism by which PCB affects DA remains unclear. It is now known that some PCB congeners have a structural configuration that facilitates binding to an aryl hydrocarbon (Ah) receptor like other polychlorinated compound s, including 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD). Some PCB c ongeners, on the other hand, have structural characteristics, e.g., no n-coplanarity, that diminish access to the Ah receptor. Non-TCDD-like PCB congeners that appear in the brain following in vivo exposure demo nstrate the highest potency in terms of decreasing DA content in PC-12 cells and inhibiting calcium homeostasis mechanisms in vitro. The bio logical significance of the effects of the PCBs on DA content or calci um homeostasis with regard to the behavioral and neurological effects observed following developmental exposure in vivo is not clear. Recent research, however, suggests that PCBs can alter a number of physiolog ical processes that may be important for development. For example, PCB -induced alterations in thyroid function during development may underl ie some of the developmental effects of PCBs reported in humans and an imal models. Additional research on the PCBs seems warranted in a numb er of areas, including the: 1) structural requirements necessary for b inding to the Ah-receptor, 2) mechanism(s) of PCB-induced alterations in DA content and calcium homeostasis in vitro, 3) relationship betwee n observed neurochemical effects in vitro and effects in vivo, and 4) relationship between PCB-induced neurochemical effects and crucial dev elopmental processes such as those controlled by thyroid hormone devel opment. (C) 1997 Intox Press, Inc.