Whole embryo culture and toxicity testing

Abstract

The use of post-implantation embryo culture in toxicity testing has been the subject of research as well as debate. Advantages of the method include reduced animal use, and reduced cost and time in comparison with in vivo testing. In addition, the method yields many developmental endpoints: it allows the direct and controlled addition of small amounts of compounds, and the incorporation of metabolizing systems is possible. Disadvantages include the technical skill required, the restricted culture duration, the artificial route of administration of test compounds and the absence of the maternal compartment (and hence the absence of a measure for adult toxicity). Several studies using a variety of compounds have shown promising results with respect to correlations between in vivo effects and the outcome of embryo culture. The question of how a meaningful validation study should be designed is still a matter of dispute. Issues under discussion include: the purpose of validation, culture conditions, endpoint definition, choice of compounds to be tested, the status of in vivo data on test compounds, presentation of results, double-blind and interlaboratory design, and the position of the test within a testing strategy. The validity of whole embryo culture as a toxicity screening test is likely to vary considerably between classes of compounds. Therefore, validation studies with larger sets of related compounds may be more meaningful than those with many unrelated compounds. Whole embryo culture may provide a significant contribution to risk assessment by use in screening, and for mechanistic, structure-activity, and dose-response studies.