Structure‐Toxicity Relationships for α, β‐Unsaturated Alcohols in Fish

Abstract

AbstractPrevious toxicity testing with fathead minnows (Pimephales promelas) indicated that some unsaturated acetylenic and allylic alcohols can be metabolically activated, via alcohol dehydrogenase, to highly toxic α, β‐unsaturated aldehydes and ketones or allene derivatives. Although several in vivo and in vitro toxicological and biochemical endpoints can differentiate these alcohols by toxic mechanism, the use of stereoelectronic molecular descriptors to discriminate these toxicants, and subsequently to predict potency, had not been previously attempted. Exploration of several descriptors indicated that soft electrophilic characteristics of acetylenic or allylic moieties in the suspected metabolites unambiguously discriminated reactive and narcotic toxicants. The acute toxicity of alcohols acting as narcotics was accurately predicted using an existing quantitative structure‐activity relationship for nonpolar narcosis. The toxicity of alcohols mediated by metabolic activation was estimated quantitatively using acceptor superdelocalizability of specific carbon atoms of the acetylenic or allylic moiety in the putative electrophilic intermediates.