Outliers: their origin and use in the classification of molecular mechanisms of toxicity

Quantitative structure-activity relationships (QSARs) provide a useful tool for defining a mathematical relationship between chemical structure and toxicity, and for applying such statistically derived models for predicting the toxicity of untested chemicals. Outlier chemicals can be encountered both in the derivation of QSAR models as well as in their application. Information regarding the relationship between molecular descriptors and molecular mechanism of toxicity can provide insight into the origin of outlier behavior as well as guidance regarding the predictive limitations of such models. Comparison of measured toxicity data for fish and rats with baseline QSAR prediction provides a means of identifying outliers and for categorizing more specific molecular mechanisms.