QSARs of aromatic amines: identification of potent carcinogens.

In previous investigations, we have developed Quantitative Structure-Activity Relationships (QSAR) models for a series of aromatic amines based on well defined physicochemical descriptors: these QSARs were aimed at: (a) describing the modulation of the carcinogenic potency among the active ones only; and (b) modeling the separation between carcinogens and non-carcinogens. In this analysis based on a larger range of chemicals, we checked and confirmed the validity and robustness of the previous models. Since the identification of high potency carcinogens (which pose the highest risk to human health) is particularly relevant to risk assessment, we also established a new QSAR model that points directly to aromatic amines likely to have high carcinogenic potency.

Structural motifs modulating the carcinogenic risk of aromatic amines.

The structure alerts (SA) for carcinogenicity/mutagenicity are a repository of the science on chemical biological interactions; in addition, they have a crucial role in practical applications for risk assessment. In predictive toxicology, it is crucial that knowledge of SAs is accompanied by knowledge of the structural motifs that modulate their effects. Recently, we have compiled an updated list of SAs implemented in the expert system Tox-tree 1.

The expanding role of predictive toxicology: an update on the (Q)SAR models for mutagens and carcinogens.

Different regulatory schemes worldwide, and in particular, the preparation for the new REACH (Registration, Evaluation and Authorization of CHemicals) legislation in Europe, increase the reliance on estimation methods for predicting potential chemical hazard. To meet the increased expectations, the availability of valid (Q)SARs becomes a critical issue, especially for endpoints that have complex mechanisms of action, are time-and cost-consuming, and require a large number of animals to test. Here, findings from the survey on (Q)SARs for mutagenicity and carcinogenicity, initiated by the European Chemicals Bureau (ECB) and carried out by the Istituto Superiore di Sanita' are summarized, key aspects are discussed, and a broader view towards future needs and perspectives is given.