Quantitative structure-activity relationships, based on hydrophobicity measured as the 1-octanol/water partition coefficient (Kow), have been developed for predicting the acute no-observable-effects concentration (NOEC) for fathead minnows (Pimephales promelas), using a mechanism/mode of action approach. Models were developed for nonpolar 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, a strong correlation was observed between the acute NOEC and acute lethality measured as the 50% lethal concentration (LC50) for 407 chemicals, regardless of the mechanism/mode of action. This relationship is modeled by the equation log NOEC-1 = 1.007 (log LC50) + 0.246; n = 407, r2 = 0.989, s = 0.142, f = 38095.6, and Pr > f = 0.0001. Examination of the relationship between the acute NOEC and the subchronic NOEC for four mechanisms/modes of action implies that the acute to subchronic ratio is not independent of mechanism of action. The resulting ratios were 6.42 (+/- 3.01) for nonpolar narcosis, 80.00 (+/- 17.78) for polar narcosis, 10.05 (+/- 4.59) for respiratory uncoupling, and 3.94 (+/- 1.72) for bioreactivity.
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