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Unexpected common mechanistic pathways for embryotoxicity of warfarin and lovastatin

There are new challenges for hazard and risk assessment in the chemical industry with regard to REACH legislation in Europe and related activities in the US and Japan, which require the development of novel in vitro models for the molecular characterization of drug- or chemical-related effects. In particular the investigation of developmental toxicity so far is regulated by guide lines including assessments of brain morphology, of behaviour, development of young animals, measurements of biomarkers for gliosis and cytotoxicity and more, requiring huge numbers of test animals. In the frame of a European FP6 project on reproductive toxicology ( we used protein lysates from mouse embryonic stem cells differentiated into contracting cardiomyocytes according to the validated embryonic stem cell test (EST) protocol and related ES models in a differential quantitative proteomic study to identify novel surrogate protein biomarkers for embryo toxicity.