Modeling Cytochrome P-450 Mediated Acute Nitrile Toxicity Using Theoretical Linear Solvation Energy Relationships
George R. Famini, Leland Y. Wilson, Stephen C. DeVito · ACS symposium series · 1993
A theoretical linear solvation energy relationship (TLSER) model for predicting acute nitrile toxicity was developed using molecular volume, dipolarity/polarizability, hydrogen bond (molecular orbital) acidity, and electrostatic basicity terms as descriptors. It was observed that molecular orbital acidity was the most important descriptor in the model, followed by molecular volume. The predictive quality of the TLSER model appears to be equal to that of a recently reported model that uses octanol-water partition coefficients and estimated rates of α-hydrogen atom abstraction as descriptors. Previously reported TLSER models of toxicity have largely been confined to predicting non-specific toxicity. The results of this study suggest that TLSER models may be useful in predicting specific (mechanism-based) toxicity.