INHIBITION OF ALCOHOL-DEHYDROGENASE ACTIVITY BY ACETYLENIC AND ALLYLIC ALCOHOLS - CONCORDANCE WITH INVIVO ELECTROPHILE REACTIVITY IN FISH

Acetylenic and allylic alcohols have been reported to be 20 to 5,000 times more acutely toxic to fathead minnows (Pimephales promelas) than would be expected from a narcosis-based mechanism of action. The greater-than-expected toxicity of these alcohols has been proposed to be a result of metabolic activation to the corresponding reactive alpha,beta-unsaturated aldehydes or allene derivatives. Using purified horse liver and rainbow trout (Oncorhynchus mykiss) hepatic cytosol alcohol dehydrogenase (ADH) preparations, the propensity of a series of acetylenic and allylic alcohols to inhibit enzyme activity, in both the presence and the absence of reduced glutathione, was ascertained. Those alcohols classified as reactive toxicants in acute toxicity tests were generally effective inhibitors of ADH activity, whereas those alcohols classified as narcotics were generally ineffective inhibitors. The results from this study suggest that (a) acetylenic and allylic alcohols may be metabolically activated to reactive species and (b) to compare and ultimately predict the toxicity of these unsaturated alcohols, their rates of metabolic activation and the reactivity of the subsequently produced aldehydes must be quantified.