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

Theor. models can be an efficient tool to assess compd. toxicity as an alternative to exptl. detns. Their application must follow some requirements that include the possibility of understanding the rationale that supports the prediction; here, the detn. of the mode of action (MOA) is important. A combination of similarity and reactivity anal. has been applied to group chem. compds. with the aim at selecting groups that share structure and electronic state. The model is not based on exptl. data but only on structural features. The result is a no. of groups that contains similar compds. with similar reactivity and, possibly, similar MOA. The comparison of these groups to the exptl. detd. MOAs available for the EPAFHAM database permits the discussion of the validity of both the model and the exptl. data.