Use of Molecular Descriptors in Separating Phenols by Three Mechanisms of Toxic Action

Abstract

Phenols are widely used in agriculture and various industries. Many quantitative structure-activity relationships (QSARs) have been developed for phenols. The most toxicologically meaningful QSARs have been established by separating compounds by their mechanisms of action (MOAs). However, correctly determining the MOA of a compound is not easy. Discriminant analysis was employed in this study to separate selected phenols by three MOAs (polar narcosis, weak acid respiratory uncoupling, and soft electrophilicity) using molecular descriptors as discriminating variables. Results showed that quadratic terms of several molecular descriptors were needed in addition to their linear terms as discriminating variables. Cross-validation of the linear discriminant functions showed that a small total error rate for mechanism classification was achieved.

A Toxicity Evaluation and Predictive System Based on Neural Networks and Wavelets

“…Compounds having different modes of action are toxic in different ways due to different interactions at the biomolecular level, and their eco-and biotoxic effects in any given test system generally must be predicted with different QSARs. Modes of toxic action were predicted for 336 test compounds (taken from refs [28][29][30][31] for up to 11 modes of action with 95% accuracy (see Table 1). Results for predicting the mode of action for chemical compounds on the basis of structural information (95% classification accuracy) exceed those previously reported in the literature, which generally range from 85 to 89% accuracy.…”

Two‐step Multivariate Classification of the Mechanisms of Toxic Action of Phenols

“…In each step of the algorithm, the prior probability was set proportional to the number of phenols in each mechanism category, as was done in other studies [11,12,13]. All discriminating variables (logK ow , pK a , E LUMO , E HOMO , and N hdon ) were initially entered in discriminant analysis but were subject to a backward variable selection procedure Figure 1.…”

“…Recently a statistical approach has been taken to classify phenols by their mechanisms of toxic action. This approach makes use of existing databases of phenols with a priori identified toxicity mechanisms and is based on multivariate statistical analysis, particularly discriminant analysis, of the molecular descriptors of the phenols [11,12,13]. Discriminant analysis had been used by other researchers [e.g., 2,14,15] for a similar purpose.…”