ABSTRACT
In the past three decades, numerous in vitro developmental toxicity models have been described, but this chapter focuses on those assays currently in use for industrial screening, or that have been proposed for regulatory acceptance with respect to human risk assessment. The following models will be discussed: both rodent and avian micromass cultures, embryonic stem cells (ESCs), and rodent whole embryo culture. The zebra fish model is described in another chapter. A brief overview of the history and rationale for in vitro screens is provided, but rather than restating themes of earlier excellent reviews (1-14), the critical events of the last decade will be emphasized. The most significant occurrence during this time has been the large international effort funded by European Committee for the Validation of Alternative Methods (ECVAM) to validate three embryotoxicity tests. The biology, strengths, and weaknesses of each test are compared and the important contributions made by ECVAM with respect to the generation of prediction models, the validation process, and possible regulatory acceptance are highlighted. Examples are also given pertaining to the application of in vitro developmental toxicity tests in both industrial screening and the risk assessment process. ECVAM has recommended the regulatory acceptance of these in vitro tests, and this is discussed in the context of European legislation that strives to prohibit animal testing for certain chemical product classes. Finally, several
workshops have been held to consider the limitations and possible improvements of the embryotoxicity models. Their recommendations serve as the basis for what in vitro embryotoxicity testing might look like in the future.
