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J Environ Sci Health A Tox Hazard Subst Environ Eng


Title:Estimation of chloroform inhalation dose by other routes based on the relationship of area under the blood concentration-time curve (AUC)-inhalation dose to chloroform distribution in the blood of rats
Author(s):Take M; Takeuchi T; Haresaku M; Matsumoto M; Nagano K; Yamamoto S; Takamura-Enya T; Fukushima S;
Address:"a Japan Bioassay Research Center, Japan Industrial Safety and Health Association , Hadano , Kanagawa , Japan"
Journal Title:J Environ Sci Health A Tox Hazard Subst Environ Eng
Year:2014
Volume:49
Issue:3
Page Number:253 - 261
DOI: 10.1080/10934529.2014.846191
ISSN/ISBN:1532-4117 (Electronic) 1093-4529 (Linking)
Abstract:"The present study investigated the time-course changes of concentration of chloroform (CHCl3) in the blood during and after exposure of male rats to CHCl3 by inhalation. Increasing the dose of CHCl3 in the inhalation exposed groups caused a commensurate increase in the concentration of CHCl3 in the blood and the area under the blood concentration-time curve (AUC). There was good correlation (r = 0.988) between the inhalation dose and the AUC/kg body weight. Based on the AUC/kg body weight-inhalation dose curve and the AUC/kg body weight after oral administration, inhalation equivalent doses of orally administered CHCl3 were calculated. Calculation of inhalation equivalent doses allows the body burden due to CHCl3 by inhalation exposure and oral exposure to be directly compared. This type of comparison facilitates risk assessment in humans exposed to CHCl3 by different routes. Our results indicate that when calculating inhalation equivalent doses of CHCl3, it is critical to include the AUC from the exposure period in addition to the AUC after the end of the exposure period. Thus, studies which measure the concentration of volatile organic compounds in the blood during the inhalation exposure period are crucial. The data reported here makes an important contribution to the physiologically based pharmacokinetic (PBPK) database of CHCl3 in rodents"
Keywords:"Administration, Inhalation Administration, Oral Animals Area Under Curve Chloroform/*administration & dosage/blood/*pharmacokinetics Dose-Response Relationship, Drug Inhalation Exposure Male Rats Rats, Sprague-Dawley;"
Notes:"MedlineTake, Makoto Takeuchi, Tetsuya Haresaku, Mitsuru Matsumoto, Michiharu Nagano, Kasuke Yamamoto, Seigo Takamura-Enya, Takeji Fukushima, Shoji eng England 2013/11/28 J Environ Sci Health A Tox Hazard Subst Environ Eng. 2014; 49(3):253-61. doi: 10.1080/10934529.2014.846191"

 
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