Limitations of the toxic equivalency factor approach for risk assessment of TCDD and related compounds

Halogenated aromatic hydrocarbons (HAHs), such as polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDDs), and dibenzofurans (PCDFs), are industrial compounds or by-products that have been widely identified as environmental contaminants. Hazard and risk assessment of complex HAH mixtures have utilized a toxic equivalency factor (TEF) approach, where the toxic equivalents (TEQs) of any mixture are equal to the sum of the concentration of individual (i) congeners times their potencies (TEFi) relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, TEF = 1.0). TEQ = sigma [PCDDi] x TEFi + sigma [PCDFi] x TEFi + sigma [PCBi] x TEFi. The TEQ (or TCDD equivalents) can be readily calculated from analytical data and provides an estimate of the toxicity of any mixture containing HAHs. Several in vivo and in vitro studies with some PCDD/PCDF and PCB mixtures have demonstrated correlations between experimentally determined and calculated TEQs. However, results of several studies have also shown that for specific responses, the TEQ for some HAH mixtures are non-additive. For example, PCB mixtures and individual PCB congeners such as 2,2',4,4',5,5'-hexachlorobiphenyl inhibit toxic and biochemical responses induced by TCDD and related compounds. Another problem associated with hazard and risk assessment of background exposure to HAHs is the relative contribution of trace levels of HAHs (exodioxins) compared to relatively high exposure to naturally occurring aryl hydrocarbon receptor (AhR) agonists, which act through the same mechanistic pathway.