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The European Union’s ban on animal testing for cosmetic ingredients and products has generated a strong momentum for the development of in silico and in vitro alternative methods. One of the focus of the COSMOS project was ab initio prediction of kinetics and toxic effects through multiscale pharmacokinetic modeling and in vitro data integration. In our experience, mathematical or computer modeling and in vitro experiments are complementary. We present here a summary of the main models and results obtained within the framework of the project on these topics. A first section presents our work at the organelle and cellular level. We then go toward modeling cell levels effects (monitored continuously), multiscale physiologically based pharmacokinetic and effect models, and route to route extrapolation. We follow with a short presentation of the automated KNIME workflows developed for dissemination and easy use of the models. We end with a discussion of two challenges to the field: our limited ability to deal with massive data and complex computations.

Uncertainties in material microstructure features can lead to uncertainty in damage predictions based on multiscale microstructure-property models. This paper presents an analytical approach for stochastic uncertainty analysis by using a univariate dimension reduction technique. This approach is used to analyze the effects of uncertainties pertaining to the structure-property relations of an internal state variable plasticity-damage model that predicts failure. The results indicate that the higher the strain the greater the scatter in damage, even when the uncertainties in the material plasticity and microstructure parameters are kept constant. In addition, the mathematical sensitivity analysis results related to damage uncertainty are consistent with the physical nature of damage progression. At the beginning, the initial porosity and void nucleation are shown to drive the damage evolution. Then, void coalescence becomes the dominant mechanism. And finally, when approaching closer to failure, fracture toughness is found to dominate the damage evolution process. (C) 2009 Elsevier Ltd. All rights reserved.