Comparative Quantitative Structure-Activity-Activity Relationships for Toxicity to Tetrahymena pyriformis and Pimephales promelas

An approach to predict acute aquatic toxicity, in the form of a quantitative structure-activity-activity relationship (QSAAR), is described. This study assessed relative toxic effects to fish Pimephales promelas, and a ciliate Tetrahymena pyriformis, and attempted to form relationships between tem. A good agreement between toxic potencies (R2 = 0.754) was found for a chemically diverse dataset of 364 compounds, when using toxicity to ciliate as a surrogate for that for fish. This relationship was extended by adding three theoretical structural descriptors of the molecules. The inclusion of these descriptors improved the relationship further (R2 = 0.824). The structural features that were found to improve the extrapolation between the toxicity to the two different species were related to the electron distribution of the carbon skeleton of the toxicant, its hydrogen-bonding ability, and its relative nitrogen content. Such a QSAAR approach provides a potential tool to predict the toxicities of chemicals for environmental risk assessment and thus for reducing animal tests.JRC.I.3-Toxicology and chemical substance