Determination of Toxicant Mode of Action by Augmented Top Priority Fragment Class

Theoretical models can be an efficient tool to assess compound toxicity as an alternative to experimental determinations. Their application must follow some requirements that include the possibility of understanding the rationale that supports the prediction; here, the determination of the mode of action (MOA) is important. A combination of similarity and reactivity analysis has been applied to group chemical compounds with the aim at selecting groups that share structure and electronic state. The model is not based on experimental data but only on structural features. The result is a number of groups that contains similar compounds with similar reactivity and, possibly, similar MOA. The comparison of these groups to the experimentally determined MOAs available for the EPAFHAM database permits the discussion of the validity of both the model and the experimental data. © 2013 American Chemical Society.