The COSMOS (Integrated In Silico Models for the Prediction of Human Repeated Dose Toxicity of COSMetics to Optimise Safety) Project is a unique international collaboration developing computational approaches for the prediction of repeated dose toxicity. The project comprises 15 partners from academia, industry, regulatory agencies and SMEs from across Europe and the US. Moreover, COSMOS is part of a cluster of six research projects within the SEURAT-1 (Safety Evaluation Ultimately Replacing Animal Testing) Research Initiative. Organ level toxicity involves complex mechanisms, thus it cannot be predicted by a single simplified in silico model. Therefore COSMOS is taking an innovative approach integrating different technologies, e.g. the threshold of toxicological concern approach, grouping of chemicals, (Q)SARs for toxicity prediction and modelling of biokinetics. All are being developed with a special emphasis on the mechanistic basis of the models considered. Computational workflows as well as a new comprehensive database with reliable structures and repeated dose toxicity data will be freely available to support safety assessment without the use of animals and will thus contribute to the 3Rs. The international dimension is important for the development and especially regulatory acceptance of the models proposed, the international companies having to assure the safety of their products on a global scale. Therefore industry, regulatory agencies and NGOs in Europe and the US are involved either as project partners or as external experts.