Halonitriles, which are disinfection by-products, have been detected in chlorinated water supplies. Although several halonitriles are shown to be mutagenic and carcinogenic, very little is known about organ or systemic toxicity and the biologic fate of these chemicals. Our objectives are to study the relationship between halonitrile biotransformation and toxicity. Specifically we plan: a) To clarify the biologic fate of toxic doses of halocentonitrile and halopropionitrile and to determine the uptake and extent of molecular interactions at target tissue sites. b) To determine in vivo the extent of metabolism to cyanide, halide and other metabolic products and to determine the effect of alterations of drug metabolizing enzymes on the biotransformation and toxicity of halonitriles. c) To elucidate in vitro the bioorganic mechanism of cyanide and halid liberation from halonitriles. Use of 14C-labeled compounds will facilitate studies on metabolism, distribution, and molecular interactions at target organs, and prevent """"""""missing"""""""" unanticipated metabolic products. The significance of the proposed research is not restricted to elucidation of molecular toxicity and metabolism of the mentioned halonitriles. The study of simple molecules with characterized modes of reaction and a relatively restricted number of metabolites may guide prediction of the potential toxicity of more complex molecules.
Showing the most recent 10 out of 28 publications
