The use of embryonic stem cells for regulatory developmental toxicity testing in vitro--the current status of test development.

The future chemical policy of the European Union as well as the 7th amendment of the cosmetic directive is calling for the development of alternative tests to animal experimentation for toxicological safety testing. In the field of embryotoxicity one of the most promising in vitro models are based on embryonic stem cells. The embryonic stem cell test has already been validated in comparison to in vivo results in an international blind collaboration study. The presented review is discussing the use, limitations and further needs for the test in order to be fully suitable for regulatory acceptance. In this context, it is summarized which requirements for an in vitro embryotoxicity test have to be fulfilled for regulatory toxicity testing. In addition, an overview about the current status of test development of other embryonic stem cell tests is presented. Several workshops have reviewed the progress of in vitro tests for developmental toxicity testing. A general consensus of these workshops has been that one single test will not be sufficient to cover all manifestations of developmental toxicity. The establishment of a test battery for developmental toxicity is required. This will be even more challenging since the principles of a composing test strategy and its validation have not been defined yet. Finally, the unique possibility of combining the human embryonic stem cell technology and the microarray techniques might lead to a deeper understanding of the toxicological mechanisms of human developmental toxicants.