双环醇甲醚的遗传毒性和胚胎毒性研究，双环醇的主要杂质。

Genotoxicity and Embryotoxicity Study of Bicyclol Methyl Ether, Main Impurity in Bicyclol.

机构信息

New Drug Safety Evaluation Center, Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing, 100050, China.

Beijing Union Pharmaceutical Factory, Beijing, 100026, China.

出版信息

Chin J Integr Med. 2019 Oct;25(10):743-749. doi: 10.1007/s11655-018-2553-x. Epub 2018 Sep 22.

DOI:10.1007/s11655-018-2553-x

PMID:30242590

Abstract

OBJECTIVE

To assess the genotoxicity and embryotoxicity of bicyclol methyl ether (BME), the main impurity in bicyclol.

METHODS

Five concentrations of BME (0.5, 5, 50, 500 and 5000 μg/plate) were used in the Ames test to detect gene mutation. In the chromosome aberration test, Chinese hamster lung cells were used to detect chromosomal aberration of BME (15, 30, 60, 120 μg/mL) with or without S9 mixture. Embryotoxicity test was also conducted to determine any embryotoxicity of BME (7.5, 22.5, 67.5 μg/L) using zebrafish embryos.

RESULTS

No significant differences were observed in the Ames test and the chromosome aberration test in the BME groups compared with the vehicle control group. The zebrafish embryos toxicity test also showed no embryo development toxicity of BME, including hatching rate, body length, pericardial area and yolk sac area.

CONCLUSIONS

Bicyclol methyl ether has no genotoxicity in vitro and embryotoxicity in zebrafish embryos, and the impurity in bicyclol is qualified.

摘要

目的

评估双环醇甲醚（BME）的遗传毒性和胚胎毒性，BME 是双环醇的主要杂质。

方法

采用 Ames 试验检测 BME（0.5、5、50、500 和 5000μg/平板）的 5 个浓度，以检测基因突变。在染色体畸变试验中，使用中国仓鼠肺细胞检测 BME（15、30、60、120μg/mL）有无 S9 混合物时的染色体畸变。还进行了胚胎毒性试验，以确定 BME（7.5、22.5、67.5μg/L）对斑马鱼胚胎的任何胚胎毒性。