ABSTRACT

TCDD is but one of 75 chlorinated dibenzo-p-dioxins. There are 135 chlorinated dibenzofurans, 209 polychlorinated biphenyls, and hundreds of polychlorinated naphthalenes, azo-and azoxy-benzenes, as well as terphenyls, quarterphenyls, and biphenylenes. In addition, there are brominated congeners and mixed bromo-chloro compounds in these structural classes. Only a small subset of these compounds are approximate isostereomers of TCDD. However, those that are fully laterally substituted and can assume a planar conformation, can act as full or partial agonists, bringing about the same spectrum of responses. The first step. in the action of all dioxin-like compounds is interaction with a cellular protein known as the Ah receptor (reviewed in Birnbaum, 1994a). Halogenated aromatics which do not bind to this receptor with high affinity do not bring about the same effects as TCDD. A rank order of binding to the Ah receptor with numerous effects such as enzyme induction, thymic atrophy, and even lethality has been well demonstrated. However, it is important to note that compounds that do not bind to the Ah receptor may have their own spectrum of adverse effects via independent mechanisms, that is, because a compound is not TCDD-Iike does not mean it is nontoxic.