Novel Immuno-Bioassay for Dioxin Toxicity Assessment

Halogenated dioxins and related compounds are widespread environmental contaminants. Such"dioxin-like" compounds are typified by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3-,4,7,8pentachlorodibenzofuran (PCDF), and 3,3 ',4,4' ,5 pentachlorobiphenyl (PCB). These toxins haveprofound acute and chronic effects in birds and mammals, including humans. The toxic effects ofcompounds like TCDD are dependent on their ability to transform the Ah receptor. We have developeda simple in vitro bioassay for transformation of the Ah receptor. The assay is capable of detecting thepresence of Ah transforming compounds such as TCDD. One potential use for this assay would be thedetermination of toxic equivalency factors (TEFs) of complex mixtures of dioxin-like compounds. Thedetermination of TEFs of complex and uncharacterized mixtures of dioxin-like compounds is critical forenvironmental monitonng and cleanup, risk assessment, exposure assessment, and molecular toxicologyresearch. Existing methods to determine TEFs of complex mixtures are not commercially acceptable dueto the need for live cells, radioactivity, or sophisticated equipment. We propose the determinetoxicological relevance of measuring the in vitro transformation of the Ah receptor. These studies willprovide a bioassay acceptable to a wide variety of scientists involved in dioxin toxicology research.