Collaborative work on evaluation of ovarian toxicity 2) Two- or four-week repeated dose studies and fertility study of mifepristone in female rats
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- Tamura Toru
- Toxicology Research Laboratory, R&D, Kissei Pharmaceutical Co., Ltd.
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- Yokoi Ryohei
- Toxicology Research Laboratory, R&D, Kissei Pharmaceutical Co., Ltd.
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- Okuhara Yuji
- Toxicology Research Laboratory, R&D, Kissei Pharmaceutical Co., Ltd.
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- Harada Chiho
- Toxicology Research Laboratory, R&D, Kissei Pharmaceutical Co., Ltd.
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- Terashima Yukari
- Toxicology Research Laboratory, R&D, Kissei Pharmaceutical Co., Ltd.
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- Hayashi Morimichi
- Toxicology Research Laboratory, R&D, Kissei Pharmaceutical Co., Ltd.
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- Nagasawa Tatsuya
- Toxicology Research Laboratory, R&D, Kissei Pharmaceutical Co., Ltd.
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- Onozato Tomoya
- Toxicology Research Laboratory, R&D, Kissei Pharmaceutical Co., Ltd.
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- Kobayashi Kazuo
- Toxicology Research Laboratory, R&D, Kissei Pharmaceutical Co., Ltd.
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- Kuroda Junji
- Toxicology Research Laboratory, R&D, Kissei Pharmaceutical Co., Ltd.
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- Kusama Hiroshi
- Toxicology Research Laboratory, R&D, Kissei Pharmaceutical Co., Ltd.
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抄録
In order to assess ovarian pathological changes and their relationship to changes in female fertility parameters, mifepristone, a progesterone receptor antagonist, was selected as the test article and was administered orally to female rats at dose levels of 0, 0.8, 4, 20 and 100 mg/kg for 2 or 4 weeks in repeated dose-toxicity studies and in a female fertility study at dose levels of 0, 0.8, 4 and 20 mg/kg from > 2 weeks before copulation to postcoital day 7. In the repeated dose toxicity studies, persistent estrus was seen in the vaginal smears, and multiple cysts in the ovaries at necropsy, increases in luteinized cysts and hypertrophy of previously formed corpora lutea were observed in the histopathological examination of ovaries in rats receiving 20 mg/kg or more for 2 or 4 weeks. In female fertility studies, persistent vaginal cornification was also observed at 20 mg/kg and the precoital interval was significantly shortened. All of the animals were completely infertile when dosed with 20 mg/kg during the post-coital period. An increase in pre-implantation losses was observed in the animals treated with 20 mg/kg during the pre-coital phase, while treatment with 4 mg/kg mifepristone during the post-coital phase induced an increase in post-implantation losses. These results suggested that a 2-week administration period would be sufficient to detect the ovarian toxicity of mifepristone in repeated dose toxicity study and the pathological findings in the ovaries would reflect the alterations in female reproductive endpoints in the female fertility study.
収録刊行物
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- The Journal of Toxicological Sciences
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The Journal of Toxicological Sciences 34 (Special), S31-S42, 2009
一般社団法人 日本毒性学会
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詳細情報 詳細情報について
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- CRID
- 1390001204900124800
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- NII論文ID
- 110007114383
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- NII書誌ID
- AN00002808
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- ISSN
- 18803989
- 03881350
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- NDL書誌ID
- 10177375
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
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