Review of (Q)SARs for Mammalian Toxicity

The proposed REACH (Registration, Evaluation and Authorisation of Chemicals) regulation calls for reducing of animal testing by using alternative methods. QSAR (Quantitative structure–activity relationship) approaches provide a valuable means of achieving this goal. Compared with the QSAR modelling of ecotoxicological endpoints, the modelling of mammalian toxicity is more complicated. The main problem is related to wide variations in the quality and accuracy of the in vivo data, in the organisms used, and also in the complexity and poor understanding of the mechanisms involved, especially for longer-term effects. Nevertheless, there have been numerous efforts to develop QSAR models in this field. This paper reviews QSAR models for the mammalian toxicity published in the last ten years. A number of QSAR models based on cytotoxicity data from mammalian cell lines are also included because of their possible use as a surrogate of acute toxicity to mammals. The models identified are evaluated as useful tool for predictive purposes and also for better understanding of the multiple mechanisms involved in the toxicity. However, there is still need for more sufficiently characterized models in accordance with OECD validation principles that will be useful to predict the regulatory endpoint as required in the future REACH system.