Research into the mechanism of toxicity of PCBs has focused on the Ah receptor. However, it is becoming increasingly clear that certain ortho- chlorine-substituted, non-coplanar PCB congeners having low affinity for the Ah receptor exhibit important biological activities. Actions of non-coplanar PCB congeners in a variety of biological systems have been discovered and the mechanisms for these effects are being elucidated. The objectives of this symposium are to examine the state of knowledge concerning the mechanisms of toxic action of non-coplanar PCBs and to identify similarities and differences using a variety of biological systems. Effects to be considered will include: neurotoxicity, estrogenicity, insulin release, neutrophil function, calcium regulation, and relevant signal transduction systems. Finally, the symposium addresses the need to consider non-coplanar congeners within the context of risk assessment. The use of Ah-receptor binding and its associated biological effects to assess the total toxicity of PCBs may no longer be defensible because of the actions produced by non-coplanar congeners. This symposium provides documentation for that conclusion and focuses attention on emerging mechanisms of PCB action that have received relatively little attention to date. The topics presented should be of interest to toxicologists interested in mechanisms of action, in PCB risk assessment, and in regulatory toxicology.
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