Biological degradation of TCDD in rats

Abstract

Apart from its high toxicity^1,2, the chemical stability and persistence of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the environment bring about additional hazards^3,4. However, until now there has been no evidence for degradation of this dioxin in biological systems, and it is considered unusual that a compound which is insusceptible to biological attack should be so extremely toxic. In in vitro studies⁵ with microsomal preparations from mouse, rat and rabbit liver, as well as in vivo, no metabolite of TCDD has been detected by several workers^6–8. Recent data, showing a lower toxicity of TCDD in rats after stimulation of the hepatic mixed-function oxidase, suggested possible metabolic transformation of this compound⁹. In the present study, we used tritiated TCDD to search for metabolites in the bile of rats and found marked changes in lipophilicity and mobility in TLC of the excreted radioactivity. Treatment with diazomethane yielded at least two new compounds. These observations hinted at the formation of phenolic hydroxyl groups in the dioxin molecule.