Comparison of Fish Toxicity Screening Data and QSAR Predictions for 48 Aniline Derivatives

Abstract

A comparison was made of the predicted fish LC50 values for 48 aniline derivatives with literature 24-hr screening data. The predictions were made based upon the log P and pK_A parameters and the QSAR equations of Hermens. The required log P and pK_A values were obtained from experimental measurements, and also calculated directly from chemical structures. Twenty-four of the tested compounds produced sickness or lethality in at least one test. For seven of these compounds, tests had been performed at more than one concentration with effects observed only at the higher concentration, from which an approximate toxicity threshold could be estimated. In general, the QSAR predictions agreed semi-quantitatively with the available screening data. A lack of observed effect for compounds predicted to show toxicity at the tested concentrations was ascribed to inadequate time to achieve a steady state equilibrium, limiting water solubility, or a combination of both of these factors. Several compounds exhibited toxicity at concentrations significantly below those predicted; these results were interpreted in terms of electrophile or proelectrophile mechanisms.