Quantitative structure-activity relationships for estimating the no-observable-effects concentration (NOEC) in fathead minnows (Pimephales promelas)

Using a mechanism/mode of action approach, quantitative structure-activity relationships (QSARs), based on hydrophobicity measured as the 1-octanol/water partition coefficient (K_ow), have been developed for estimating the acute no observable- effects concentration (NOEC) for fathead minnows (Pimephales promelas). These include models for estimating the toxicity of non-polar narcotics, amine narcotics, polar narcotics, ester narcotics and respiratory uncouplers. A set of bioreactive chemicals were evaluated, but models based on hydrophobicity alone are inadequate for these chemicals. Additionally, examination of the relationship between the acute NOEC and acute lethality measured as the 50% lethal concentration (LC₅₀) revealed, regardless of the mechanism/mode of action, that there is a strong correlation between the two effects. This relationship is modeled by the equation, log NOEC^-1 = 1.008 (log LC₅₀) + 0.247; n = 407, r² = 0.989, s = 0.142, f=38095.6 and Pr > f = 0.0001. The relationship between the acute NOEC and the sub-chronic NOEC was examined for four mechanisms/modes of action. The resulting ratios were 6.42 (±3.01) for non-polar narcosis, 80.00 (± 17.78) for polar narcosis, 10.05 (± 4.59) for respiratory uncoupling, and 3.94 (± 1.72) for reactivity. The variation implies that the acute to subchronic ratio is not independent of mechanism of action.