SD大鼠胚胎-胎仔发育毒性试验背景数据的建立

Background data on embryo-fetal development toxicity studies in SD rats

目的总结上海市计划生育科学研究所(中国生育调节药物毒理检测中心)SD大鼠胚胎-胎仔发育毒性试验中各检测指标的数据,建立SD大鼠胚胎-胎仔发育毒性试验指标的背景数据,为药物生殖毒性安全性评价提供参考。方法从本中心2010-2018年SD大鼠胚胎-胎仔发育毒性试验中,总结10批溶媒对照组孕大鼠的胚胎发育和胎仔生长发育指标数据,包括孕大鼠的妊娠期体质量、妊娠结局(平均黄体数、平均着床数、平均活胎数、吸收胎和死胎)、胎仔生长发育(胎重、身长和尾长)及胎仔外观、内脏和骨骼,将数据进行统计,计算各指标的均值、标准差和变异系数。结果总结了217只孕大鼠和2506只胎仔的胚胎-胎仔发育指标。孕大鼠妊娠第0天(GD0)体质量为(222±22)g,GD0-1的摄食量为每只(18.9±3.8)g·d-1;GD20体质量为(353±30)g,GD19-20的摄食量为每只(26.2±4.0)g·d-1。GD20安乐死并剖宫检查,妊娠率为95.2%,孕大鼠平均黄体数为(12.8±2.1)个,平均着床数为(11.8±2.8)个,平均活胎数为(11.5±2.8)只,活胎率为97.9%,吸收胎率为2.1%;胎仔发育指标中,胎仔体质量为(3.6±0.3)g,胎盘重为(0.5±0.1)g,身长为(35.7±1.5)mm,尾长为(12.9±0.4)mm,性别比(雄/雌)为1.0(1227/1279);活胎仔中,外观变异率为0.2%,内脏变异率为0.5%,骨骼变异率为7.4%。结论初步建立了本GLP实验室SD大鼠胚胎-胎仔发育毒性试验的背景数据,可为生殖毒性研究提供参考。

OBJECTIVE To establish the background data on SD rat embryo-fetal development toxicity studies by Shanghai Institute of Planned Parenthood Research(National Evaluation Center for Toxicology of Fertility Regulating Drugs),and provide reference for reproductive toxicology research.METHODS From the embryonic-fetal developmental toxicity tests of SD rats between 2010 and 2018,the index data on embryo development and fetal growth and development of pregnant rats was selected,including pregnancy body mass and pregnancy outcomes(average of corpora lutea,implantation,live fetuses,absorptions and dead fetuses),the growth and development of fetuses(fetal body mass,body length and tail length)and fetal appearance,viscera,and skeleton.The data was statistically analyzed,and the mean,standard deviation and coefficient of variation were calculated.RESULTS Totally 217 pregnant rats and 2506 fetuses were included.The body mass of pregnant rats on gestation day 0(GD0)was(222±22)g,while the food consumption of GD0-1 was(18.9±3.8)g·d-1.The body mass of GD20 was(353±30)g and the food consumption of GD19-20 was(26.2±4.0)g·d-1.GD20 euthanasia cesarean section examination showed that the pregnancy rate was 95.2%,and that the average of corpora lutea,implantation and live fetuses was 12.8±2.1,11.8±2.8 and 11.5±2.8,respectively.The rate of live fetuses and absorption rate was 97.9%and 2.1%,respectively.Among the fetal development indexes,the body mass and placental mass were 3.6±0.3 and(0.5±0.1)g,respectively.The body length was(35.7±1.5)mm,the tail length was(12.9±0.4)mm,and the sexual ratio(male/female)was 1.0(1227/1279).The external,visceral and skeletal variations were 0.2%,0.5%and 7.4%,respectively.CONCLUSION The background data on embryo-fetal toxicity studies of SD rats has been established,which can provide reference for reproductive toxicity research.