Developmental toxicity of Fuganlin oral liquid in SD rats of different ages
10.3867/j.issn.1000-3002.2023.12.002
- VernacularTitle:中药复方馥感啉口服液对不同年龄段SD大鼠发育毒性
- Author:
Jianmin GUO
1
,
2
;
Wenqiang ZHANG
;
Yinghua DENG
;
Feibiao MENG
;
Chun LIANG
;
Wei YANG
Author Information
1. 广州湾区生物医药研究院,广东莱恩医药研究院有限公司,广东省药物非临床评价研究企业重点实验室,国家中药现代化工程技术研究中心中药非临床评价分中心,广东省创新药物评价与研究工程技术研究中心,广东 广州 510990
2. 香港科技大学生命科学部,香港 999077
- Keywords:
Fuganlin oral liquid;
juvenile animal study;
juvenile rats;
developmental toxicity
- From:
Chinese Journal of Pharmacology and Toxicology
2023;37(12):895-903
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the potential developmental toxicity and delayed toxicity of Fuganline oral liquid(FGLOL)after long-term administration in juvenile SD rats via a three-stage juve-nile animal study(JAS).METHODS Stage 1:according to the proposed clinical dose for infants within one year of age,FGLOL 3.88,11.64,38.75 g·kg-1 was orally administered to rats of postnatal day 4(PND4)rats for 18 days,and the drug was stopped for 3 weeks.Stage 2:according to the proposed clinical dose for children ages 1 to 6,FGLOL 3.88,11.64,38.75 g·kg-1 was orally administered to PND15 rats for 31 d,and the drug was discontinued for 3 weeks.Stage 3:according to the proposed clinical dose for children aged 7 to 12,FGLOL 29.06,58.13,116.25 g·kg-1 was orally administered to PND40 rats for 66 d,and the drug was stopped for 4 weeks.The effects of FGLOL on health status,food intake,body mass,growth and development,nerve reflex development,learning and memory ability,physical development(body length),bone development(bone mineral density),hematology and coagulation(white blood cells,red blood cells and platelet count),blood biochemistry(glutamate dehydrogenase,urea nitrogen and triglycerides)and histopathology were investigated in young rats.RESULTS In the three-stage JAS test,long-term administration of FGLOL did not cause rat death,and no toxicological effects were observed on body mass,growth and development,nerve reflex development,physical development,bone development,hematology and coagulation,blood biochemistry and histopathology of juvenile rats compared with the vehicle control group.CONCLUSION The no observed adverse effect level(NOAEL)of FGLOL is 38.75 g·kg-1 for the JAS test corresponding to humans between 1 and 6 years old,while the NOAEL of FGLOL is 116.25 g·kg-1 for the JAS test and repeated drug toxicity test corresponding to humans aged 7 to 12.
