| 1. To define the applicability domain of EST by testing a series of selected relevant classes of chemicals.2. To improve the prediction model of the EST on the basis of the results of testing the chemical classes as mentioned above and on the basis of the biology of the model.3. To enhance the predictivity and extrapolation to the human by investigating the possibility to use alternative differentiation routes and existing human stem cell lines.4. To feed the project outcome into the scientific community and into international regulatory bodies that deal with testing strategies and guidelines (EU, OECD) The Embryonic Stem cell Test (EST) is the most extensively studied animal-free alternative for developmental toxicity testing. Current experience with the EST indicates that the applicability domain and the prediction model require further study before implementation of EST in testing strategies can be considered. We will test a series of selected classes of compounds which are of relevance in view of existing knowledge on their developmental toxicity profile. Using the data generated, the prediction model will be improved, and the optimal place of EST in the reproductive toxicity testing strategy defined.In addition, a parallel approach is aimed at improvement of the predictivity of the test in the long term by exploring alternative stem cell differentiation routes and by using existing human rather than murine ES cell lines. Finally, the outcome will be continuously communicated in existing international bodies such as EU and OECD to promote implementation of the updated EST in international testing strategies. |
