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.

Keywords:

• Chloroform
• blood concentration
• area under the blood concentration-time curve
• inhalation
• inhalation equivalent dose

Acknowledgment

We wish to express our thanks to Professor David B. Alexander, Graduate School of Medical Sciences, Nagoya City University and Mr. Yasutomo Sasaki, Japan Bioassay Research Center, Japan Industrial Safety and Health Association, for proofreading this manuscript.