Collaborative work on evaluation of ovarian toxicity 8) Two- or four-week repeated-dose studies and fertility study of Anastrozole in female rats
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- Shirai Makoto
- Medicinal Safety Research Laboratories, Daiichi-Sankyo Co., Ltd.
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- Sakurai Ken
- Medicinal Safety Research Laboratories, Daiichi-Sankyo Co., Ltd.
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- Saitoh Wataru
- Medicinal Safety Research Laboratories, Daiichi-Sankyo Co., Ltd.
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- Matsuyama Takuya
- Medicinal Safety Research Laboratories, Daiichi-Sankyo Co., Ltd.
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- Teranishi Munehiro
- Medicinal Safety Research Laboratories, Daiichi-Sankyo Co., Ltd.
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- Furukawa Tadashi
- Medicinal Safety Research Laboratories, Daiichi-Sankyo Co., Ltd.
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- Sanbuissho Atsushi
- Medicinal Safety Research Laboratories, Daiichi-Sankyo Co., Ltd.
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- Manabe Sunao
- Medicinal Safety Research Laboratories, Daiichi-Sankyo Co., Ltd.
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抄録
The main focus of this study was to determine the optimal administration period concerning the toxic effects on ovarian morphological changes in the repeated dose toxicity study. In order to assess the morphological and functional changes induced in the ovary by cyclophosphamide (CP), the compound was administrated to female rats at dose levels of 0, 5, 10 and 20 mg/kg for the repeated dose toxicity study for 2 or 4 weeks, and at 0, 5, 10, and 20 mg/kg for the female fertility study from 2 weeks prior to mating to Day 7 of pregnancy. In the repeated dose toxicity study, increases in large sized atretic follicles, atrophy of corpora lutea were observed in the 20 mg/kg group in the 4-week study by the histopathological examination of the ovaries. There were no drug-related changes in the ovary in the 2-week study. In the female fertility study, the numbers of implantation were slightly decreased and the corpora lutea of pregnancy was not observed in the 20 mg/kg group. The dose-dependent increase in the incidence of post-implantation loss was observed, and no abnormalities were observed in the estrus cycle and mating in all treated groups. From these findings, the histopathological changes in the ovary are important endpoints for the evaluation of drug-induced ovarian damage as well as caesarean section. In conclusion, a 4-week administration period is sufficient to detect the ovarian toxicity of CP in the repeated dose toxicity 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), S91-S99, 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
- 1390001204900123008
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- NII論文ID
- 110007114407
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- NII書誌ID
- AN00002808
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- ISSN
- 18803989
- 03881350
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- NDL書誌ID
- 10177414
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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
- Crossref
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可