Embryotoxicity transfer

It has been reported that embryotoxic or teratogenic effects of some compounds were detected in the New Zealand White rabbit, whereas there was no suspicion of such effects in the rat (2, 3). The origin of these differences between species has remained unelucidated in many cases. However, metabolism, systemic maternal exposure, maternal toxicity, fetal exposure, or placental transfer often explains the discrepancies. 

The EST has been developed with the aim to exploit the characteristics and differentiation potential of mouse embryonic stem cells (ES cells), established from the early embryo in 1981 [4, 5], ES cells are cultured in suspension to induce the formation of embryoid bodies, and afterwards they are transferred in 24-well dishes to allow attachment and differentiation in contracting cardiomyocytes. The toxicological endpoint is the inhibition of cardiac differentiation. In parallel a cytotoxicity test is performed on undifferentiated ES cells and a control somatic (fibroblast) cell line (3T3). The concentrations of testing chemicals that induce 50 % of differentiation inhibition (ID50) and 50 % cytotoxicity (IC50) in ES cells and 3T3 cells are inserted in a validated prediction model to classify the test chemical as non-embryotoxic, moderate, or strong embryotoxic [2, 6, 7], The validation of the method has been... 

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