For a Michael-acceptor set of 45 α,β-unsaturated esters, the 2^nd-order rate constant of reaction with glutathione, log k_GSH, was modeled through the quantum chemical reaction barrier (ΔE^≠) employing methane thiol as model nucleophile. Regression of their 48-h toxicity toward the ciliates Tetrahymena pyriformis (log EC₅₀, 50 % growth inhibition) on log K_ow (octanol/water partition coefficient) and log k_GSH revealed a variation in the relative weights of hydrophobicity and electrophilic reactivity as determinants of the aquatic toxicity. The difference D_Kk=log K_ow−log k_GSH turned out as a suitable means for predictively discriminating between narcosis-level (D_Kk>3.0) and excess-toxic (D_Kk<2.0) compounds. In the intermediate D_Kk range (2.0≤D_Kk≤3.0), both narcosis-level and reactive-toxicity models are applicable for predicting aquatic toxicity. As such, D_Kk represents the chemoavailability of Michael-acceptor esters, characterizing their likelihood for undertaking covalent reactions with thiol sites of endogenous peptides and proteins. At the same time, D_Kk introduces a straightforward way for characterizing the applicability domain of QSAR (quantitative structure-activity relationship) models for predicting the toxicity of Michael-acceptor esters. The resultant model suite comprising QSARs for reactive toxicity and baseline narcosis is triggered by the compounds’ chemoavailability, and yields predictions superior to existing approaches.