A QSAR study of the acute toxicity of some industrial organic chemicals to goldfish. Narcosis, electrophile and proelectrophile mechanisms

Abstract

1. A baseline toxicity QSAR model was derived for the 24-h LC₅₀ to the goldfish, Carassius auratus.

2. The QSAR-predicted LC₅₀ values for six epoxide derivatives were 2.8–985 times greater than measured. The excess toxicity of these epoxides and other compounds was ascribed to an electrophile molecular mechanism involving S_N² reaction with sulphydryl and other neucleophile groups present in enzymes and other biological macromolecules.

3. The exčess toxicities of allyl alcohol and pentaerythritol triallyl ether were interpreted in terms of proelectrophile mechanisms. For the latter compound, this involves a monooxygenase-mediated free radical proton abstraction to a stable allyl radical. The allylfree radical can undergo enzymic free radical hydroxylation to afford the corresponding acetal, which on decomposition yields the Michael cceptor electrophile acrolein.