Development of bioassays and approaches for the risk assessment of 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds.

Polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and related halogenated aromatic hydrocarbons (HAHs) are industrial compounds or by-products that have been identified as contaminants in almost every component of the global ecosystem. 2,3,7,8- Tetrachlorodibenzo-p-dioxin (TCDD) is the most toxic HAH, and studies in rodents have shown that this compound is a carcinogen. Analysis of environmental samples for HAHs has shown that these extracts contain complex mixtures of isomers and congeners, and this greatly complicates risk assessment due to the paucity of data available for most of the individual compounds. Extensive research has demonstrated a common receptor-mediated mechanism of action for TCDD and related toxic HAHs, and this has led to the development of a mechanism-based risk assessment approach for HAHs. Toxic equivalency factors (TEFs; relative potency compared to TCDD) have been developed for selected HAH congeners, and the TEF values can be used to determine "toxic equivalents" (TEQs) for HAH mixtures. In addition, several bioassays that use receptor-mediated end points have been developed and can be used directly to determine the TEQs for HAH mixtures. The applications of the TEF/TEQ approach for the risk assessment of HAHs are considerable, particularly with the conversion of complex analytical data into TEQs. However, there appear to be several limitations to this approach, particularly with PCBs because their potential nonadditive (antagonistic), interactive effects with "2,3,7,8-TCDD-like" compounds may invalidate the use of the risk assessment procedure for some environmental matrices.