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KMID : 0379520000160030201
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한국독성학회지
2000 Volume.16 No. 3 p.201 ~ p.209
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Uterotrophic Activity of Ethinyl Estradiol by Gavage and Subcutaneous Administration in Immature Female Rats
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Chung Moon-Koo
Lim Kwang-Hyeon
Kim Jong-Choon
Kim Young-Hee
Suh Jeong-Eun
Ha Chang-Su
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Abstract
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In association with the international validation program to establish a rodent uterotrophic assay, we conducted preliminary uterotrophic assay proposed by GECD using immature female rats. In the present study, oral and subcutaneous routes were chosen to compare the effects of estrogenic com-pounds in the two dosing regimens. The reference compound ethinyl estradiol (EE) and the antagonist ZM189154(ZM) were administered by gavage or subcutaneously (s.c.) to immature female SD rats from 20 to 22 days of age. For each study, sixty-six female rats were randomly assigned to eleven groups: Untreated control, EE 0,0.01, 0.03, 0.1, 0.3, 1.0,3.0 and 10.0 mutextrm{g}/kg, EE 3.0 mutextrm{g}/kg(gavage)/0.3 mutextrm{g}/kg(s.c) & ZM 0.1 mg/kg, and EE 3.0 mutextrm{g}/kg(gavage)/0.3 mutextrm{g}/kg (s.c) & ZM 1.0 mg/kg. There were no treatment-related changes in clinical signs, body weights, food consumption, and necropsy findings in any groups of two studies. The wet and blotted uterus weights increased dose-dependently. Histopathological examination revealed that diameter of uterine duct, height of uterine luminal epithelium. and height oj vaginal epithelium increased dose-dependently. The proliferating cell nuclear antigen (PCNA) immunoreactive cells were increased in number dose-dependently. The estrogenic effects observed in the present studies occurred at geq 0.3 mutextrm{g}/kg of oral dose and geq 0.1 mutextrm{g}/kg of s.c. dose. An antagonistic effect of ZM against EE was found in both uterus weight and histopathological parameters. From the results obtained, it can be concluded that dose-dependence of the uterotrophic assay using EE and ZM was well demonstrated by gavage and subcutaneous administration and that the estrogenic effects of EE by s.c. dose were higher than those by gavage administration. In addition, blotted uterus weight was more sensitive than wet uterus weight and vaginal epithelial height was found to be the most sensitive parameter among the parameters examined.
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KEYWORD
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Endocrine disrupting chemicals, In vivo screening assay, Ethinyl estradiol, Estrogen, Uterus weight, Immature female rat
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