QSAR pre-screen of 70,983 substances for genotoxic carcinogenicity, mutagenicity and developmental toxicity in the EU FP7 project ChemScreen

The focus of the EU FP7 project ChemScreen, which was completed by the end of 2013, was to generate alternative testing methods for reproductive toxicity under REACH. If found adequate, QSARs can be applied in REACH as a replacement for animal tests. As no testing for reproductive effects should be performed in REACH on known genotoxic carcinogens or germ cell mutagens with appropriate risk management measures implemented, a QSAR pre-screen for genotoxic carcinogenicity, germ cell mutagenicity and (limited) developmental toxicity was included in the project. Predictions for estrogenic and anti-androgenic activity (in vitro) were also included in the pre-screen. The prediction set comprised 70,983 of the 143,835 chemicals REACH pre-registered chemicals, for which structural information was found and was suitable for the applied QSAR models. The prediction set was run through 16 models and decision algorithms were applied to combine the predictions from the individual models to reach overall predictions for genotoxic carcinogenicity, germ cell mutagenicity and developmental toxicity. Furthermore, the full list of REACH pre-registered substances (143,835) was searched for substances containing certain known toxic heavy metals (Cd, As, Hg and Pb) and these were flagged as they may be assumed to possess the properties of the heavy metal part unless otherwise known. The QSAR pre-screen results were fed into subsequent ChemScreen activities to develop an in vitro/in silico screening system to predict human- and ecotoxicological effects.