Routine teratogenicity test that uses chick embryos in vitro

An in vitro culture of chicken embryo is described: the embryos at the stage of gastrulation are explanted from eggs into transparent silicone chambers where they continue to develop normally under controlled conditions for additional 3 d. This period corresponds to 2-5 wk of postconceptional age in the human embryo. In both the chick and man, this period is very sensitive to physicochemical perturbations which can lead to surviving malformations. Six chemical agents were tested with this culture: methotrexate, cadmium chloride, caffeine, phenobarbital, aspirin, and saccharin. Survival scores, growth perturbations, and early signs of anomalies of the nervous, skeletomotor, and cardiovascular systems were analyzed with respect to the used concentrations. The dose-response curves were obtained with good precision and allowed a discrimination between the teratogenetic and unspecific toxic effects and a comparison of the toxic potency of the six drugs. The evaluation of one drug took, roughly, 3 wk, one technician, and about 150 eggs. The advantages (simplicity, rapidity, reproducibility, specificity, economy, no suffering, and no use of mature animals) and disadvantages (nonmammalian species, absence of detoxicating organs) of the method are discussed. The method is proposed as a routine teratogenicity and embryotoxicity test which allows primary screening of many compounds and which can thus substantially reduce the ultimate experiments that use pregnant mammalian females.