Structural Alerts of Mutagens and Carcinogens

This paper summarizes the evidence on the Structural Alerts of mutagenicity and carcinogenicity. The Structural Alerts are molecular substructures or reactive groups that are related to the carcinogenic and mutagenic properties of the chemicals, and represent a sort of "codification" of a long series of studies aimed at highlighting the mechanisms of action of the mutagenic and carcinogenic chemicals. The identification of the Structural Alerts has had a great value both in terms of understanding mechanisms, and of assessing the risk posed by chemicals. This mini-review illustrates a number of case studies where the Structural Alerts have played a fundamental role in risk assessment, and describes recent work aimed at expanding or refining the knowledge on the Structural Alerts through the use of Artificial Intelligence and Data Mining approaches. As a matter of fact, the 1980's were the years during which the Quantitative Structure-Activity Relationships (QSAR) approach was having a dramatic development, with an exponential increase in methods and computerized technologies proposed, and the more qualitative approach based on the simple recognition of toxicophores was entering into shade. This is even more so today. However, the knowledge of the toxicophores, as recognition and classification of the molecular substructures and reactive groups responsible for the toxic effects, is still at the basis of the mechanistic science of toxicology and provides powerful means of intervention to "domesticate" the