ABSTRACT
OBJECTIVE To summarize the data on embryo-fetal developmental toxicity study of rabbits, and to establish the background data so as to provide reference for drug reproductive toxicology research. METHODS From the embryo-fetus developmental toxicity study of rabbits in our laboratory between 2011 and 2018, all the data on control groups was selected, including rabbits' pregnancy mass, outcomes of pregnancy (the average number of corpus lutea, implantation, live fetuses, fetal absorption rate, fetal live rate, fetal absorption rate), fetal growth and development (mass, crown-rump length and tail length) and fetal variation (appearance, viscera and skeleton). The mean and standard deviations of each index were calculated. RESULTS The embryo-fetal development indexes of 149 pregnant rabbits and 1097 fetuses were summarized. The gestational age of rabbits was about 3-5 months, and the body mass was (3.0±0.3) kg on gestation day 0 (GD0), and (3.5±0.4) kg on GD28. These rabbits were euthanized and cesarean section examination showed that the pregnancy rate was 85.6%, the average of corpus lutea number was 8.0±2.1, the average number of implantations was 7.6±2.1, the average number of live fetuses was 7.4±2.1, the live rate was 96.2%, the absorption rate was 1.9%, and the death rate was 1.8%. Among the fetal development indicators, fetal body mass was (33.4±5.0) g, placental weight was (4.0±0.8) g, crown-rump length was (86.3±5.9) mm, tail length was (11.3±0.8) mm, and sex ratio (male/female) was 1.0 (550/547). The rate of appearance variation (or malformation) was 0.18%, skeleton variation (or malformation) was 33.5%, and visceral variation (or malformation) was 0.09%. CONCLUSION The background data of the embryo-fetal developmental toxicity study of rabbits is established in our laboratory. The changes of each index are stable, and the spontaneous deformity rate of fetuses is low.
ABSTRACT
To study the chronic hepatotoxicity of Chinese medicine Zishen Yutai pill (ZYP) prepared from Polygonum multiflorum with the recommended dosage in normal Beagle dogs. Low, middle and high doses of ZYP (1.5, 3.0, 6.0 g·kg⁻¹; i.e. 3×, 6× and 12× equivalent doses) were given orally to dogs for 39 consecutive weeks. At the same time, the same volume of deionized water was used as the solvent control group, one time a day. The general condition of the animals was observed every day during the period of administration, and the blood was collected before and 13, 26, 39, 43 weeks after administration to detect the biomarkers related to the hepatotoxicity of the dog serum. 2/7, 3/7 and 2/7 animals were dissected after 13, 39, and 43 weeks of administration to observe the pathological changes of the animal organs, weigh the mass of main organs and conduct pathological examination of the liver. As compared to the solvent control group, 11 liver hepatotoxicity traditional biomarkers such as ALT, AST were found no ZYP-related changes at month 3, 6, 9 of the administration and month 1 in recovery period; There was no significant difference in liver viscera index and liver pathology. Therefore, no obvious hepatotoxicity was shown by ZYP administered up to 6.0 g·kg⁻¹ for 9 months in normal dogs at doses of 1.5, 3.0, and 6.0 g·kg⁻¹.