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. (C) 2011 Elsevier Inc. All rights reserved.