Classification and Quantification of the Toxicity of Chemicals to Guppy, Fathead Minnow, and Rainbow Trout. Part 2. Polar Narcosis Mode of Action

• Published in: QSAR & combinatorial science Vol. 28; no. 2; pp. 163 - 174
• Main Authors: Raevsky, Oleg A., Grigor'ev, Veniamin Yu, Dearden, John C., Weber, Eric E.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01-02-2009; WILEY‐VCH Verlag
• Subjects: HYBOT; MOLDIVS; Polar narcosis; Toxicity
• ISSN: 1611-020X; 1611-0218
• DOI: 10.1002/qsar.200860016

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+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.