Model Suite for Predicting the Aquatic Toxicity of [alpha],[beta]-Unsaturated Esters Triggered by Their Chemoavailability

For a Michael-acceptor set of 45 [alpha],[beta]-unsaturated esters, the 2nd-order rate constant of reaction with glutathione, logkGSH, was modeled through the quantum chemical reaction barrier ([Delta]E≠) employing methane thiol as model nucleophile. Regression of their 48-h toxicity toward the ciliates Tetrahymena pyriformis (logEC50, 50% growth inhibition) on logKow (octanol/water partition coefficient) and logkGSH revealed a variation in the relative weights of hydrophobicity and electrophilic reactivity as determinants of the aquatic toxicity. The difference DKk=logKow-logkGSH turned out as a suitable means for predictively discriminating between narcosis-level (DKk>3.0) and excess-toxic (DKk