Dose exploration of retinoic acid induced multiple external abnormalities in rats

XIA Min-jie; MIAO Jian-cheng; WANG Yu-zhu; TIAN Fang; WANG Xiao-dong; DING Xun-cheng; LI Wei-hua; HU Jing-ying

Abstract：Objective: To explore teratogenic effects of different doses of retinoic acid (RA) in SD rats, and provide scientific basis for selecting positive control drug of teratogenicity tests. Methods: Pregnant SD rats were randomly allocated into 4 groups: 50 mg·kg-1 RA group, 100 mg·kg-1 RA group, 150 mg·kg-1 RA group and corn oil group. They were administered via gavage with RA at gestation date (GD) 10 with doses of 50, 100, 150 mg·kg-1 and corn oil for four group. The multiple external abnormalities in rat embryos were observed and recorded at GD 20 after pregnant rats were sacrificed. Results: Multiple external abnormalities in rat embryos were clearly observed in all three RA-treated groups with teratogenetic rate of 100％. The main abnormalities included agnathia, rachischisis, exophthalmos, strephenopodia, symmelia, anury or short tail, short or small fetus. Omphalocele and hyposarca could be observed occasionally. The phenotype and occurrence rate of abnormalities in the three RA-treated groups were highly consistent and repeatable. There was no significant difference in the rate of embryo abnormalities in the three dose groups (P＜0. 05), but the degree of abnormality increased with the dose. Significant absorption or stillbirth were observed in 100 and 150 mg·kg-1 RA-treated groups, and the rate of absorption andstillbirth increased with the dose. Conclusion: 50 mg·kg-1 RA could induce significant teratogenic effects in SD rats with no increasing rates of absorption and stillbirth. Under the current experimental conditions, the 50 mg·kg-1 RA was considered to be the optimized dose for rat teratogenicity test.