Estimating relative potency for receptor-mediated toxicity: Reevaluating the toxicity equivalence factor (TEF) model

Once considered an interim procedure for use with mixtures of polychlorinated dibenzo-p-dioxins and dibenzofurans, use of the toxicity equivalence factor (TEF) model has been proposed for other groups of structurally similar chemicals. Data from polychlorinated dibenzo p-dioxins and polychlorinated dibenzofurans as web as theoretical analyses of the biological basis for receptor-mediated toxicity demonstrate the limitations of this model and indicate that estimation of equivalent doses for such chemicals is more likely to require a function than a point estimate such as a TEF. Relatively small changes in the TEFs can result in both significant changes in the estimated dose for the mixture and the percentage of the estimated risk that is attributable to the most potent or reference compound. Estimates of equivalent doses are likely to become less accurate when extrapolated to lower responses which frequently serve as the basis for regulatory decisions. Existing models allow the relative potency to be a function rather than a point estimate as well as interaction at the receptor among the chemicals. (C) 1997 Academic Press.