9.9. USE OF TOXICITY EQUIVALENCE

The concept of toxicity equivalence in evaluating mixtures of dioxin-like compounds is fundamental to many of the conclusions reached in this characterization. This is based on the fact that most data described in this and preceding chapters were obtained using 2,3,7,8-TCDD as the experimental compound. More limited data exist as individual congeners are evaluated. Nonetheless, estimates of body burden as derived in this reassessment suggest that greater than 90% of the total dioxin equivalence is due to dioxin-like compounds other than 2,3,7,8-TCDD. While there are empirical bases for the toxicity equivalence factors assigned to dioxin-like compounds relative to 2,3,7,8-TCDD, they generally represent order of magnitude estimates of relative toxicity and are not meant to be used precisely. The potency for most, if not all, of the toxic end points is determined by the number and position of the halogen (chlorine or bromine) atoms on the dioxin-like molecule. This appears, based on a substantial body of evidence, to be a function of relative ability to bind to a specific cellular receptor that mediates most, if not all, of the toxic end points of this class of compounds. This inference is based on experimental evidence, primarily in rodents but involving some other species, that for some toxic effects, the potency of the effect itself is proportional to receptor binding as measured by either binding studies or a sensitive measure of receptor binding, AHH induction. When ED_50s for effects versus binding are plotted logarithmically, good linear correlations are obtained (Safe, 1990). This approach constitutes a "relative ranking" scheme based on 2,3,7,8-TCDD. Because the data base for effects for individual congeners is incomplete and because the concept is based on responsiveness of humans to these compounds in a manner similar to that of animals and high to low dose extrapolation, the TEQ approach is considered a useful but uncertain procedure.

In addition to the idea of "relative ranking," there is a second aspect to the TEQ approach. This is the concept of additivity. The hypothesis is that one can estimate the toxicity of a mixture of dioxin-like compounds by adding together the products of the concentrations of the individual congeners and their TEFs. This hypothesis has not been extensively tested although data addressing this issue are generally supportive of additivity. Some data collected using high levels of different congeners have suggested the potential for interactions (mostly, antagonism) between congeners. There is currently general acceptance of the concept of additivity with the recognition that issues such as congener interactions, presence of "spare" receptors, and the unavoidable presence of other dietary constituents that react with the dioxin receptor must be considered to add uncertainty to the concept.