QSAR for methyl- and/or chloro-substituted anilines and the polar narcosis mechanism of toxicity

Abstract

The relative toxicity of 32 methyl- and/or chloro-substituted anilines was assessed in the 48-h sublethal, static Tetrahymena pyriformis population growth assay. Quantitative structure-activity relationships (QSARs) were examined. Regression analysis of toxicity (log IGC 50 −1) versus the 1-octanol/water partition coefficient (log K OW) showed excellent correlation as revealed by the equation log IGC 50 −1 = 0.698 (log K OW) −1.190; n= 23, r-square= 0.931, s= 0.136, f= 282.47, Pr > f= 0.0001. This equation is considered to represent the polar narcosis mode of action. Nine derivatives were not included in the model. The parent compound aniline and the 4-chloro derivative were observed to be more toxic than predicted. The seven di- and trimethyl derivatives were observed to be less toxic than predicted. The latter seven derivatives could be included in the model with the addition of the summation of the Hammett sigma constants (∑σ) as a second descriptor, log IGC 50 −1 = 0.428 (log K OW) + 0.733 (∑σ) −0.828; n= 30, r-square= 0.919, s= 0.169, f= 153.60, Pr > f= 0.0001. Abiotic loss was not considered to be a factor in the observed toxicities.