Feasibility study of the zebrafish assay as an alternative method to screen for developmental toxicity and embryotoxicity using a training set of 27 compounds

To anticipate to increased testing needs for reproductive toxicity and 3R approaches, we studied zebrafish embryo/larva as an alternative for animal testing for developmental toxicity and embryotoxicity and evaluated a training set of 27 compounds with a standardized protocol. The classification of compounds in the zebrafish embryo/larva assay, based on a prediction model using a TI (teratogenic index) cut-off value of 2, was compared to available animal and human data. When comparing the classification of compounds in the zebrafish embryo/larva assay to available animal classification, a sensitivity of 72% and specificity of 100% were obtained. The predictive values obtained in comparison to a limited set of human data were 50, 60% respectively for teratogens, non-teratogens.Overall, we demonstrated that the zebrafish embryo/larva assay, may be used as screening tool for prioritization of compounds and could contribute to reduction of animal experiments in the field of developmental toxicology.

► Zebrafish assay as alternative method for developmental toxicity testing. ► Feasibility study using a training set of 27 compounds. ► Definition of an optimized prediction model. ► High concordance established between zebrafish and animal data. ► Suitable method for screening and prioritization of compounds.