Collaborative work on evaluation of ovarian toxicity by repeated-dose and fertility studies in female rats
スポンサーリンク
概要
- 論文の詳細を見る
The National Institute of Health Sciences (NIHS) and 18 pharmaceutical companies of the Japan Pharmaceutical Manufacturers Association (JPMA) have conducted a validation study intended to evaluate whether a 2-week repeated general toxicity period with histopathological examination is sufficient to detect ovarian toxicity or not. The current repeated dose general toxicity study is considered to be insufficient in terms of evaluating female reproductive function due to a lack of evidence indicating that it is adequate. Evaluation of ovarian toxicity by comprehensive histopathological examination of the female reproductive organs based on the underlying morphology of a normal cycle of the reproductive tract including the ovary and additional immunohistochemical staining with proliferative cell nuclear antigen (PCNA) to identify small follicles may be a good tool to assess female reproductive function. In the collaborative study, 2- or 4-week repeated dose toxicity studies with ovarian histopathological examinations were conducted. A female fertility study was also conducted to compare the results with those of the ovarian histopathological findings. A total of 17 test substances were evaluated and categorized into hormone analogues, primordial follicle damaging agents, metabolite imbalance inducers, and endocrine imbalance inducers. Based on the results, ovarian toxicity could be detected by a careful histopatholgical examination. A 2-week dosing period may be sufficient for the evaluation of ovarian toxicity, except for cytotoxic compounds such as alkylating agents. The pathological findings of ovarian toxicity (decreases in follicles, increases in atretic follicles, increases in currently formed corpora lutea, etc) reflected the female fertility parameters (irregular estrous cycle, pre-implantation loss).
- 日本トキシコロジー学会の論文
著者
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Sagami Fumio
第一三共安全性研究所
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Sagami Fumio
Drug Safety Research Laboratories Eisai Co. Ltd.
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Sagami Fumio
Subcommittee Of Non-clinical Evaluation Drug Evaluation Committee Japan Pharmaceutical Manufacturers
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Sagami Fumio
Department Of Drug Safety Research Eisai Kawashima Research Laboratories Eisai Co. Ltd.
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Komatsu Shinichi
Non-clinical Evaluation Subcommittee Drug Evaluation Committee Japan Pharmaceutical Manufactures Ass
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Ohno Yasuo
第一三共安全性研究所
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SANBUISSHO Atsushi
Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd.
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Kumazawa Toshihiko
Safety Assessment Laboratory Sanwa Kagaku Kenkyusho Co. Ltd.
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Kumazawa Toshihiko
Pharmaceutical Research Laboratories Sanwa Kagaku Kenkyusho Co. Ltd.
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Yoshida Midori
National Institute of Health Sciences
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Hisada Shigeru
Safety Research Department Developmental Research Center, ASKA Pharmaceutical Co., Ltd.
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Kudo Satoshi
Research Center, Kyorin Pharmaceutical Co., Ltd.
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Ube Masayuki
Safety Research Laboratory (Kazusa), Mitsubishi Tanabe Pharma Corporation
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Komatsu Shinichi
Pre-Clinical Development Department, Development & Medical Affairs Division, GlaxoSmithKline K.K.
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Ohno Yasuo
National Institute of Health Sciences
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Kudo Satoshi
Research Center Kyorin Pharmaceutical Co. Ltd.
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Ube Masayuki
Safety Research Laboratory (kazusa) Mitsubishi Tanabe Pharma Corporation
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Yoshida Midori
Biological Safety Research Center National Institute Of Health Sciences
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Yoshida M
National Agricultural Research Center For Hokkaido Region
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Yoshida Midori
Division Of Pathology National Institute Of Health Sciences
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Hisada Shigeru
Safety Research Department Developmental Research Center Aska Pharmaceutical Co. Ltd.
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Hisada Shigeru
Safety & Pharmacokinetics Research Department Teikoku Hormone Mfg. Co. Ltd.
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Hisada Shigeru
Safety Research Department Aska Pharmaceutical Co. Ltd.
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Yoshida M
Genomic Sciences Center Riken
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Yoshida Midori
National Agricultural Research Center For Hokkaido Region
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Yoshida Midori
Dept.pathol. Sasaki Inst.
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Komatsu Shinichi
Pre-clinical Development Department Development & Medical Affairs Division Glaxosmithkline K.k.
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Matsuda Yuzuru
President Kyowa Hakko Kogyo Co. Ltd.
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Matsuda Yuzuru
Tokyo Research Laboratories Kyowa Hakko Kogyo Co. Ltd.
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Yoshida M
National Food Research Institute
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Sanbuissho Atsushi
Medicinal Safety Research Laboratories Daiichi Sankyo Co. Ltd.
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Yamasaki M
Biofrontier Laboratories Kyowa Hakko Kogyo Co. Ltd.
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Sanbuissho Atsushi
Medicinal Safety Res. Laboratories Daiichi Sankyo Co. Ltd.
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Ohno Yasuo
National Inst. Of Health Sci. Tokyo Jpn
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Yoshida M
Kyowa Hakko Kogyo Co. Ltd. Tokyo Jpn
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Kumazawa T.
Pharmaceutical Research Laboratories Sanwa Kagaku Kenkyusho Co. Ltd.
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Ohno Yasuo
Toxicogenomics Project National Institute Of Biomedical Innovation:national Institute Of Health Scie
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Sagami Fumio
Drug Safety Research Laboratories Eisai Co. Ltb.
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