EFFECTS OF DIETHOFENCARB ON THYROID FUNCTION AND HEPATIC UDP-GLUCURONYLTRANSFERASE ACTIVITY IN RATS
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概要
- 論文の詳細を見る
To examine the mechanism and toxicological significance of thyroidal tumor observed slightly in a long-term rat study with diethofencarb (isopropyl 3,4-diethoxycarbanilate), male Sprague-Dawley rats were fed diethofencarb in diets at concentrations of 0, 5,000 or 20,000 ppm for 3 months. Examinations mainly for thyroid functions including thyroid uptake of ^<125>I, serum thyroid hormone and thyroid stimulating hormone (TSH) level, hepatic UDP-glucuronyltransferase (UDP-GT) activity and histopathological examination in thyroid were performed at week 13. Decreases of body weights and food consumptions were observed at and above 5,000 ppm. Under these conditions, decrease of serum free T_4 and increase of serum TSH level were observed only at 20,000 ppm, concurrently with liver weight increase at and above 5,000 ppm and increase of hepatic UDP-GT activity at 20,000 ppm. However, no compound related effects were noted in thyroid weight, thyroid uptake of ^<125>I and gross or histopathological examination in thyroid. These results indicate that the administration of diethofencarb leads to an increase in UDP-GT activity and acceleration of thyroid hormone excretion from the liver. The acceleration causes a decrease in serum free T_4 level, triggering the feedback mechanism of the pituitary gland, promotion of TSH release and consequently an increase in serum TSH level. Thus, the slightly higher incidence of thyroid follicular cell tumors observed in the chronic and oncogenicity study with non-genotoxic diethofencarb is considered to be caused by these weak pituitary-thyroid hormonal imbalances. The toxicological significance in humans is extremely low according to the well established facts that the chronic TSH stimulatin would not induce thyroid tumors in humans and humans may be less sensitive than rats in regard to the response to goitrogenic stimuli.
- 日本トキシコロジー学会の論文
- 1992-08-25
著者
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YAMADA Tomoya
Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd.
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OKUNO Yasuyoshi
Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd.
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SEKI Takaki
Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd.
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WATANABE Tomoyuki
Environ. Health Science Lab., Sumitomo Chem. Co., Ltd.
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Seki Takaki
Environmental Health Science Laboratory Sumitomo Chemical Co. Ltd.
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Sukata Tokuo
Environmental Health Science Lab. Sumitomo Chemical Co. Ltd.
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細川 暁
Drug Safety & Disposition Research Laboratories Eisai Co. Ltd.
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Yamada T
Environmental Health Science Laboratory Sumitomo Chemical Co. Ltd.
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Yoshioka Kaoru
Environmental Health Science Laboratory Sumitomo Chemical Company Ltd.
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Yamada H
Faculty Of Pharmaceutical Sciences Kyushu University
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HOSOKAWA Shunji
Environmental Health Science Laboratory, Sumitomo Chemical Co., LTD.
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Hosokawa S
Drug Safety & Disposition Research Laboratories Eisai Co. Ltd.
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Hosokawa Shunji
Environmental Health Science Laboratory Sumitomo Chemical Co. Ltd.
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Yanai T
United Graduate School Of Veterinary Sciences Gifu University
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Nakamura J
Laboratory Of Animal Ecology Department Of Ecology And Systematics Graduate School Of Agriculture Ho
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NAKAMURA Jun
Environmental Health Science Lab., Sumitomo Chemical Co., Ltd.
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MURAKAMI Masakazu
Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd.
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INEYAMA Mariko
Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd.
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YAMADA Hirohiko
Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd.
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Okuno Yasuyoshi
Environmental Health Science Laboratory Sumitomo Chemical Company Ltd.
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Okuno Yasuyoshi
Environmental Health Science Laboratory Sumitomo Chemical Co. Ltd.
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Ineyama Mariko
Environmental Health Science Laboratory Sumitomo Chemical Co. Ltd.
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Murakami M
Univ. Tokyo Tokyo
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Watanabe Tomoyuki
Environmental Health Science Laboratory Sumitomo Chemical Co. Ltd.
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Seki Takaki
Environmental Health Science Laboratory Sumitomo Chem. Co. Ltd.
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Okuno Yasuyoshi
Environmental Health Science Laboratory Sumitomo Chemical Co. Ltd
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