Discrimination of the acute toxicity of chemicals to guppy (Poecilia reticulata), fathead minnow (Pimephales promelas) and rainbow trout (Oncorhynchus mykiss) with nonpolar narcosis and other Modes Of Action (MOA) was successfully carried out by means of discrimination analysis and structural similarity analysis. Good QSARs for acute aquatic toxicity of chemicals with nonpolar narcosis MOA for the three fish species were constructed, based on molecular polarizability and H-bond acceptor factors calculated by the HYBOT program. These latter relationships are useful alternatives to QSARs based on the experimental parameter log K o/w because they yield good statistics and because they are amenable to physicochemical interpretation. In this case, the acute aquatic toxicity of chemicals with nonpolar MOA is presented as the result of two contributions (molecular polarizability, which is volume-related, and hydrogen bonding) with opposite action: molecular polarizability increases acute nonpolar narcosis toxicity and H-bond acceptor ability decreases it.

This paper is devoted to the classification of chemicals with polar narcosis Mode of Action (MOA) to guppy, fathead minnow and rainbow trout, and to creation of QSARs for toxicity prediction of such chemicals on the basis of physicochemical descriptors calculated by the HYBOT program. More than 85% of all chemicals were correctly classified (polar narcosis/other MOA, polar narcosis/baseline toxicity (nonpolar narcosis), polar narcosis þ baseline toxicity/other MOA) on the basis of structural similarity. Regression equations with good statistical criteria using HYBOT physicochemical descriptors were obtained for the toxicity of chemicals with polar narcosis MOA.Comparison of those equations with the equations for baseline toxicity permitted estimation of the essential contribution of baseline toxicity to the toxicity of all chemicals with polar narcosis MOA. The ratio of polar and nonpolar contributions depends on hydrophobity. Such behavior can be related to the increased opportunity of a hydrophobic chemical to move in all directions in the hydrocarbon-like interior of the membrane.