A COMPARATIVE STUDY ON THE RELIABLILITY OF TOXICOKINETIC PARAMETERS FOR PREDICTING HEPATOTOXICITY OF DDT IN RATS RECEIVING A SINGLE OR REPEATED ADMINISTRATION
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概要
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A comparative study on the reliability of toxicokinetic parameters for predicting hepatotoxicity was conducted in male F344 rats receiving a single (106 mg/kg by gavage) or 7-day repeated (1000 ppm in feed, 97 mg/kg/day) administration of p,p'-DDT. DDT was selected as the test substance because it is known as a hepatotoxic agent and its metabolic pathway is well documented. Concentrations of DDT and its metabolites (DDE and DDD) in the plasma, brain, and liver were measured at various time intervals during the study and the results were compared with the area under the concentration-time curve (AUC) in relation to hepatotoxic response. Increases in the absolute and relative (ratio to body weight) liver weights were observed as a typical toxic response after a single or repeated exposure to DDT. The coefficient (R^2) of correlation between the increases in the relative liver weight and the concentrations or AUG of DDT and its metabolites in the plasma and liver was estimated. The values of R^2 between the relative liver weight and AUC of DDT or the total DDT (T-DDT) in the plasma and liver were found to be more consistent and higher than those with their concentrations in the repeated dose study. In addition, the R^2 values in correlation with their AUCs after a single exposure were lower than those in the repeated dose study. These results indicate that the AUC of DDT or T-DDT in the plasma and liver would be more reliable than their concentrations for predicting hepatotoxicity caused by DDT, especially in the repeated dose study.
- 日本トキシコロジー学会の論文
- 2003-12-26
著者
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Harada Takanori
The Institute of Environmental Toxicology
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Harada Tomoko
協和醗酵工業
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Harada Tomoko
Toxicological Research Laboratories Kyowa Hakko Kogyo Co. Ltd.
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Takeda Makio
The Institute of Environmental Toxicology
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原田 孝則
The Institute of Environmental Toxicology
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武田 真記夫
Institute Of Environmental Toxicology
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Takeda M
Kobe-university
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WATANABE Minoru
Department of Pharmacology, St. Marianna University School of Medicine
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TOMIYAMA Naruto
The Institute of Environmental Toxicology
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武田 真記夫
The Institute of Environmental Toxicology
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Tomiyama N
The Institute Of Environmental Toxicology
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Takeda Makio
Department Of Biomedical Science Faculty Of Agriculture The University Of Tokyo
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WATANABE Momiko
The Institute of Environmental Toxicology, Toxicology Division
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KOBAYASHI Hiroko
The Research Institute of Japan Plant Protection Association
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Kobayashi Haruo
Department Of Veterinary Medicine Faculty Of Agriculture Iwate University
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Watanabe Mayumi
Medicinal Safety Research Laboratories Sankyo Co. Ltd.
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Kobayashi Hiroko
Environmental Science Team Research Institute Of Japan Plant Protection Association
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Watanabe M
The Institute Of Environmental Toxicology
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Watanabe Minoru
Dep. Of Pharmacology St. Marianna Univ. School Of Medicine
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WATANABE Momiko
The Institute of Environmental Toxicology
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