Neurochemical effects of polychlorinated biphenyls: an overview and identification of research needs.
The PCBs are members of the halogenated hydrocarbon class of environmental chemicals that includes the dibenzofurans and dioxins. The PCBs were 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 banning of their manufacture in 1977. The PCBs continue to be of concern to environmental toxicologists because of their persistence in the environment and reports that exposure to relatively low levels may be associated with subtle behavioral and neurological deficits, particularly if exposure occurs during development. Developmental neurotoxicity of PCBs has been reported in humans and confirmed in several laboratory animal species, including non-human primates. During the last 20 years, there has been an attempt to understand the cellular bases of PCB-induced 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 compounds, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Some PCB congeners, on the other hand, have structural characteristics, e.g., non-coplanarity, that diminish access to the Ah receptor. Non-TCDD-like PCB congeners that appear in the brain following in vivo exposure demonstrate the highest potency in terms of decreasing DA content in PC-12 cells and inhibiting calcium homeostasis mechanisms in vitro. The biological significance of the effects of the PCBs on DA content or calcium 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 physiological processes that may be important for development. For example, PCB-induced alterations in thyroid function during development may underlie some of the developmental effects of PCBs reported in humans and animal models. Additional research on the PCBs seems warranted in a number of areas, including the: 1) structural requirements necessary for binding to the Ah-receptor, 2) mechanism(s) of PCB-induced alterations in DA content and calcium homeostasis in vitro, 3) relationship between observed neurochemical effects in vitro and effects in vivo, and 4) relationship between PCB-induced neurochemical effects and crucial developmental processes such as those controlled by thyroid hormone development.
Tilson
H A
HA
Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Kodavanti
P R
PR
D000818:Animals; D001921:Brain / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D009498:Neurotoxins / Q000633:toxicity*; D018377:Neurotransmitter Agents / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects
D009498:Neurotoxins; D018377:Neurotransmitter Agents; D011078:Polychlorinated Biphenyls