Prediction of acute mammalian toxicity from QSARs and interspecies correlations

Abstract

With the ever-growing number of xenobiotics that can potentially contaminate the environment, the determination of their mammalian toxicity is of prime importance. In this context, LD50 tests on rats and mice have been used for a long time to express the relative hazard associated with the acute toxicity of inorganic and organic chemicals. However, these laboratory tests encounter important hurdles. They are costly, time consuming and actively opposed by animal rights activists. Moreover, new legislation policies, such as REACH (Registration, Evaluation, Authorization and Restriction of Chemicals), aim at reducing the use of toxicity tests on vertebrates. Consequently, there is a need to find alternative methods for estimating the acute mammalian toxicity of chemicals. The quantitative structure–activity relationships (QSARs) and interspecies correlations appear particularly suited to reaching this goal. In this context, this paper reviews more than 150 models aiming at predicting rat and mouse LD50 values from molecular descriptors or (and) ecotoxicity data. The interest of these computational tools is discussed.