Zebrafish embryo developmental toxicity test using ICH S5 reference compounds-Investigation of the cause of false negative judgment by measuring the concentration in the embryo-

Abstract

We previously tried to validate a zebrafish (ZF) embryo developmental toxicity test using 28 positive reference compounds (described on the Reproduction and Developmental Toxicity Test Guideline of the International Conference on Harmonization of Pharmaceutical Regulations), and found that the eight compounds were false negative. In the present study, the concentration of some false-negative compounds in the ZF embryo was measured. Based on the results of the experiments, the restriction of uptake of cytarabine with very low log P (-2.7) might be the cause of false negatives.