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.
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.
authors.affiliation: a Japan Bioassay Research Center, Japan Industrial Safety and Health Association , Hadano , Kanagawa , Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Take
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Haresaku
authors.forename: Michiharu
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Kasuke
authors.initials: K
authors.lastname: Nagano
authors.forename: Seigo
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Takeji
authors.initials: T
authors.lastname: Takamura-Enya
authors.forename: Shoji
authors.initials: S
authors.lastname: Fukushima
mesh_terms: D000280:Administration, Inhalation; D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D002725:Chloroform / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D019570:Inhalation Exposure; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002725:Chloroform