LIMITATIONS OF THE TOXIC EQUIVALENCY FACTOR APPROACH FOR RISK ASSESSMENT OF TCDD AND RELATED-COMPOUNDS

Halogenated aromatic hydrocarbons (HAHs), such as polychlorinated biph enyls (PCBs), dibenzo-rho-dioxins (PCDDs), and dibenzofurans (PCDFs), are industrial compounds or by-products that have been widely identifi ed as environmental contaminants. Hazard and risk assessment of comple x HAH mixtures have utilized a toxic equivalency factor (TEF) approach , where the toxic equivalents (TEQs) of any mixture are equal to the s um of the concentration of individual (i) congeners times their potenc ies (TEFi) relative to 2,3,7,8-tetrachlorodibenzo-rho-dioxin (TCDD, TE F = 1.0). TEQ = Sigma[PCDDi] . TEFi + Sigma [PCDFi] . TEFi + Sigma [PC Bi] TEFi The TEQ (or TCDD equivalents) can be readily calculated from analytical data and provides an estimate of the toxicity of any mixtur e containing HAHs. Several in vivo and in vitro studies with some PCDD /PCDF and PCB mixtures have demonstrated correlations between experime ntally determined and calculated TEQs. However, results of several stu dies have also shown that for specific responses, the TEQ for some HAH mixtures are non-additive. For example, PCB mixtures and individual P CB congeners such as 2,2',4,4',5,5'-hexachlorobiphenyl inhibit toxic a nd biochemical responses induced by TCDD and related compounds. Anothe r problem associated with hazard and risk assessment of background exp osure to HAHs is the relative contribution of trace levels of HAHs (ex odioxins) compared to relatively high exposure to naturally occurring aryl hydrocarbon receptor (AhR) agonists, which act through the same m echanistic pathway. (C) 1998 Wiley-Liss, Inc.