Uterotrophic assay, Hershberger assay, and repeated 28-day oral toxicity study of flumorph based on the Organization for Economic Co-operation and Development draft protocols.
To evaluate the endocrine-mediated effects of flumorph, we performed the uterotrophic assay, the Hershberger assay, and the repeated 28-day oral toxicity study based on the OECD draft protocols. In the uterotrophic assay, female ovariectomized SD rats were subcutaneously injected with flumorph at doses of 0, 50, 150, and 500 mg/kg on each of 3 days, and no changes were observed. In the Hershberger assay, castrated male SD rats were administered with flumorph by oral gavage at doses of 0, 50, 150, and 500 mg/kg/day for 10 consecutive days, and no abnormal changes were observed. However, in the repeated 28-day oral toxicity study , flumorph was orally administered at doses 0, 30, 100, and 300 mg/kg/day for at least 28 days, a significantly increase in T(4) value in male rats and TSH value in female rats were detected in the highest dosage group, respectively. Besides, the flumorph administration increase liver weights, produce hepatocellular diffuse fatty degeneration, and effect biochemical parameters related to liver function in male and/or female rats in dosed groups. Therefore, flumorph is concluded to have thyroid disruption effects and is likely a thyroid disrupter, but the further studies are needed for hazard identification.
Zhao
Jian
J
Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, Liaoning Province, PR China. zll0625@yahoo.cn
Cai
Leiming
L
Wang
Jie
J
Wu
Yingliang
Y
Yao
Baoyu
B
Zhang
Le
L
D000818:Animals; D001681:Biological Assay / Q000379:methods*; D001835:Body Weight / Q000187:drug effects; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D005837:Genitalia, Male / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017408:Guidelines as Topic; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D009025:Morpholines / Q000633:toxicity*; D019055:No-Observed-Adverse-Effect Level; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D051381:Rats; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D036401:Toxicity Tests, Chronic / Q000379:methods*; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D052244:Endocrine Disruptors; D009025:Morpholines; C528737:flumorph