title: Embryo-fetal development toxicity of honokiol microemulsion intravenously administered to pregnant rats.
abstract: The aim of this study was to evaluate the embryo-fetal development toxicity of honokiol microemulsion. The drug was intravenously injected to pregnant SD rats at dose levels of 0, 200, 600 and 2000 μg/kg/day from day 6-15 of gestation. All the pregnant animals were observed for body weights and any abnormal changes and subjected to caesarean-section on gestation day (GD) 20; all fetuses obtained from caesarean-section were assessed by external inspection, visceral and skeletal examinations. No treatment-related external alterations as well as visceral and skeletal malformations were observed in honokiol microemulsion groups. There was no significant difference in the body weight gain of the pregnant rats, average number of corpora lutea, and the gravid uterus weight in the honokiol microemulsion groups compared with the vehicle control group. However, at a dose level of 2000 μg/kg/day, there was embryo-fetal developmental toxicity observed, including a decrease in the body length and tail length of fetuses. In conclusion, the no-observed-adverse-effect level (NOAEL) of honokiol microemulsion is 600 μg/kg/day, 75 times above the therapeutic dosage and it has embryo-fetal toxicity at a dose level of 2000 μg/kg/day, which is approximately 250 times above the therapeutic dosage.
authors.affiliation: New Drug Safety Evaluation Center, Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing, 100050, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Beijing Union-Genious Pharmaceutical Technology Ltd., Beijing, 100176, China.
authors.forename: Xiangfeng
authors.initials: X
authors.lastname: Ye
authors.affiliation: Beijing Union-Genious Pharmaceutical Technology Ltd., Beijing, 100176, China.
authors.forename: Lingzhi
authors.initials: L
authors.lastname: Wang
authors.affiliation: Beijing Union-Genious Pharmaceutical Technology Ltd., Beijing, 100176, China.
authors.forename: Bangjie
authors.initials: B
authors.lastname: Peng
authors.affiliation: Beijing Union-Genious Pharmaceutical Technology Ltd., Beijing, 100176, China.
authors.forename: Yingxue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: New Drug Safety Evaluation Center, Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing, 100050, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Bao
authors.affiliation: New Drug Safety Evaluation Center, Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing, 100050, China.
authors.forename: Wanfang
authors.initials: W
authors.lastname: Li
authors.affiliation: New Drug Safety Evaluation Center, Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing, 100050, China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Wei
authors.affiliation: New Drug Safety Evaluation Center, Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing, 100050, China.
authors.forename: Aiping
authors.initials: A
authors.lastname: Wang
authors.affiliation: New Drug Safety Evaluation Center, Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing, 100050, China. Electronic address: jinhongtao@imm.ac.cn.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Jin
authors.affiliation: School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China. Electronic address: chenshizhong66@163.com.
authors.forename: Shizhong
authors.initials: S
authors.lastname: Chen
mesh_terms: D000818:Animals; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000187:drug effects* / Q000473:pathology; D004655:Emulsions; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000473:pathology; D005865:Gestational Age; D007275:Injections, Intravenous; D017705:Lignans / Q000008:administration & dosage / Q000633:toxicity*; D018811:Maternal Exposure; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000633:toxicity*; D019055:No-Observed-Adverse-Effect Level; D011247:Pregnancy; D017207:Rats, Sprague-Dawley; D018570:Risk Assessment; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D001713:Biphenyl Compounds; D004655:Emulsions; D017705:Lignans; D018696:Neuroprotective Agents; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols
keywords: Cerebral ischemia protection; Embryo-fetal development toxicity; Honokiol microemulsion