A new parameter that supports speculation on the possible mechanism of hypothyroidism induced by chemical substances in repeated-dose toxicity studies
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- Yamada Takashi
- Chemical Management Center, National Institute of Technology and Evaluation
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- Hasegawa Ryuichi
- Chemical Management Center, National Institute of Technology and Evaluation
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- Nishikawa Satoshi
- Chemical Management Center, National Institute of Technology and Evaluation
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- Sakuratani Yuki
- Chemical Management Center, National Institute of Technology and Evaluation
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- Yamada Jun
- Chemical Management Center, National Institute of Technology and Evaluation
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- Yamashita Tatsuhiro
- BioIT Business Development Office, Fujitsu Limited
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- Yoshinari Koichi
- Graduate School of Pharmaceutical Sciences, Tohoku University
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- Yamazoe Yasushi
- Graduate School of Pharmaceutical Sciences, Tohoku University
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- Kamata Eiichi
- Biological Safety Research Center, National Institute of Health Sciences
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- Ono Atsushi
- Biological Safety Research Center, National Institute of Health Sciences
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- Hirose Akihiko
- Biological Safety Research Center, National Institute of Health Sciences
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- Hayashi Makoto
- BioSafety Research Center
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抄録
Hypothyroidism induced by xenobiotic treatment was analyzed for possible underlying mechanism(s) on the basis of different responses of the thyroid gland and the liver, using a newly-created database of repeated-dose toxicity of 500 chemicals. Two mechanisms are proposed: direct inhibition of thyroid hormone biosynthesis in the thyroid gland, and stimulated degradation of thyroid hormone by induction of hepatic drug-metabolizing enzymes. In the database there were 10 chemicals inducing hypertrophy/hyperplasia of follicular cells in the thyroid gland and having data on thyroid glands. On the basis of the chemical structure and information available in the literature, we judged three chemicals to be typical thioamide derivatives that act directly on the thyroid gland, and the others as non-thioamide derivatives that were unlikely to have any direct action on the thyroid gland. All these chemicals were classified into two groups using the ratios of relative weight increase rate of thyroid gland versus that of the liver. These values were at least 1.7, but 3.2 or more in the most of the cases for thioamide derivatives, and 1.2 or less for non-thioamide derivatives. This background analysis suggests the feasibility of parameter-supported speculation on the possible underlying mechanism when new repeated-dose toxicity data on hypothyroidism becomes available.
収録刊行物
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- The Journal of Toxicological Sciences
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The Journal of Toxicological Sciences 38 (2), 291-299, 2013
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
- 1390001204905206400
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- NII論文ID
- 10031151433
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- NII書誌ID
- AN00002808
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- COI
- 1:CAS:528:DC%2BC3sXnt12qtbk%3D
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- ISSN
- 18803989
- 03881350
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- NDL書誌ID
- 024645128
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- PubMed
- 23535408
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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
- PubMed
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可