Further evaluation of a teratogenicity screen using an intravitelline injection technique

A blind trial of 31 compounds was conducted in order to evaluate the intravitelline injection technique as a predictor of developmental toxicity. Rat conceptuses were explanted on day 9 of gestation and cultured until 11.5 days, at which time the compounds were injected into the vitelline circulation of the yolk sac. The embryos were then cultured for a further 24 hr after which time they were assessed on 14 parameters and assigned to one of three categories based on predetermined criteria. The results were then compared with the classifications previously allocated using data derived from in vitro studies. The compounds were examples of non-teratogens, non-cytotoxic teratogens and cytotoxic teratogens. Of the 31 compounds, 23 gave the predicted result, three non-teratogens being false positives and five teratogens having no effect in this system. The results therefore demonstrate the ability of the technique to distinguish between the three categories of compound, displaying a specificity of 75%, a sensitivity of 74% and an overall accuracy of 74.5%. Furthermore, it allowed the differentiation of active and inactive analogues of four paired compounds. This method may have applications as a teratogenicity screen or in the elucidation of the mechanism of action of teratogenic compounds.