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Toxic Equivalency Approach for Dioxins: An Example of Dose Additivity
Citation:
BIRNBAUM, L. S. Toxic Equivalency Approach for Dioxins: An Example of Dose Additivity. Presented at Modifiers of Chemical Toxicity: Implications for Human Health Risk Assessment Conference, Poros, GREECE, June 12 - 15, 2005.
Description:
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD; dioxin) is often called the most toxic man-made compound. However, it is but the prototype for a family of structurally related compounds which have a common mechanism of action, induce a common spectrum of biological responses, and are environmentally and biologically persistent. An unwanted byproduct of primarily industrial processes, it is never found alone, but as part of a complex mixture which includes other polychlorinated dioxins, dibenzofurans, and biphenyls, among others. Because of such complex exposures, the toxic equivalency (TEQ) approach, which is really a relative potency weighting scheme, has been developed for the risk assessment of these compounds. This approach is based on dose additivity in which each dioxin-like compound is given a toxic equivalency factor (TEF) which is some fraction of that of TCDD. The total TEQ = � i=1n (TEFi * massi). Parallel dose response curves have been observed for multiple endpoints, including enzyme induction, teratogenicity, immunotoxicity,tumor promotion, and cancer, among others. Equal efficacy has also been observed for compounds with only a single mechanism of action which involves binding to the Ah (or dioxin) receptor. Binary mixtures have been constructed for a variety of endpoints and dose additivity has been observed. The TEQ approach has also been found to work well for more complex mixtures, both laboratory derived and in the wild. In 1997, the World Health Organization developed consensus TEFs, which are endpoint and species independent, based on all of the available scientific data and scientific judgment. These values are currently being re-evaluated based on new data to determine if any changes in the values for 29 dioxins, furans and PCBs are warranted. Whether TEFs should be developed for additional chemicals is also under consideration. (This abstract does not reflect EPA policy.)