Validation of whole chick embryo cultures, whole rat embryo cultures and aggregating embryonic brain cell cultures using six pairs of coded compounds.

A comparative study was performed to assess the effects of six pairs of coded compounds using cultures of whole chick and rat embryos as well as aggregating brain cell cultures. Developed originally for basic studies in developmental biology, these three culture systems have been adapted for the screening of chemicals in the field of prenatal toxicology. Chick and rat embryos were cultured for 2 days during the early stages of organogenesis. Aggregating cell cultures were prepared from early foetal rat telecephalon and grown for 14 days in a chemically defined medium. Concentration-response relationships were established by treating whole embryos in vitro for 2 days, and aggregating brain cell cultures for 9 days. After decoding the compounds, the results showed that, in the three test systems, specific effects were induced at comparable concentration levels. Similar compound-related malformations could be observed in both chick and rat whole embryo cultures. In aggregating brain cell cultures, neuron- and glia-specific effects could be distinguished. Based on the results obtained in the three in vitro systems, the following concentration ranges were determined for the teratogenic/toxic potencies of the test compounds (in mol/litre): <10(-6): retinoids (Ro 13-6307, Ro 1-5488), 6-aminonicotinamide, ketoconazole; 10(-6)-10(-3): 4-hydroxypyridine, sulfadiazine, sulfanilamide, caffeine, theophylline, metronidazole, methoxyacetic acid; >10(-3): methoxyethanol. In general, the three in vitro test systems were found to provide concordant and complementary data on the toxicity and teratogenicity of a given compound. These data were also comparable with those available from in vivo studies. It is therefore concluded that such a test battery could contribute significantly to risk assessment and to the reduction of in vivo experimentation in reproductive toxicology.

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