title: A 30-day preclinical safety evaluation study of recombinant human follicle-stimulating hormone in female rhesus monkeys.
abstract: The objective of this study was to identify potential target organs for toxicity of recombinant human follicle stimulating hormone (r-hFSH) in female rhesus monkeys and to establish a no observed adverse effect level (NOAEL). In all, 24 female rhesus monkeys (Chinese origin, weighing 3.4-5.2 kg, approximately 5 years of age) received repeated subcutaneous (sc) r-hFSH at doses of 10, 60, and 300 IU/kg per d or vehicle once daily for 30 days followed by a 15-day recovery period. Endometrial hyperplasia and dermal edema in the external genitals were found in some animals at 300 IU/kg per d. Pharmacologic-related multiple cystic follicles were found in all r-hFSH-treated groups. A weak, anti-FSH antibody response was detected at the end of treatment in animals administered 60 and 300 IU/kg per d. These results indicate that the primary effects of r-hFSH in female rhesus monkeys were related to its pharmacological activity on the reproductive system. The NOAEL was considered to be 60 IU/kg per d.
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemical and Technology, Tianjin University, Tianjin, People's Republic of China.
authors.forename: Yongming
authors.initials: Y
authors.lastname: Cai
authors.forename: Zhengmin
authors.initials: Z
authors.lastname: Chen
authors.forename: Zongpeng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Longsheng
authors.initials: L
authors.lastname: Zhang
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Changxiao
authors.initials: C
authors.lastname: Liu
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004714:Endometrial Hyperplasia / Q000473:pathology; D005260:Female; D043373:Follicle Stimulating Hormone, Human / Q000008:administration & dosage* / Q000633:toxicity*; D012739:Gonadal Steroid Hormones / Q000097:blood; D007279:Injections, Subcutaneous; D008253:Macaca mulatta; D019055:No-Observed-Adverse-Effect Level; D006080:Ovarian Follicle / Q000187:drug effects*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000633:toxicity; D018675:Toxicity Tests
chemical_list: D000906:Antibodies; D043373:Follicle Stimulating Hormone, Human; D012739:Gonadal Steroid Hormones; D011994:Recombinant Proteins