Estimation of Absorption of Trihalomethanes and Carbon Tetrachloride in Low-Level Exposure by Inhalation Pharmacokinetic Analysis in Rats

Abstract.

Inhalation pharmacokinetics of the environmental contaminants chloroform, bromodichloromethane, chlorodibromomethane, and carbon tetrachloride were evaluated, and their absorption amounts were estimated in rats to obtain fundamental data for risk assessment of chronic low-level exposures. Measured amounts of the substances were injected into a closed chamber system in which a rat had been placed, and the concentration changes in the chamber were examined. The pharmacokinetics of the substances were evaluated on the basis of the concentration-time courses using linear or nonlinear compartment models. The metabolic elimination amounts at various exposure concentrations were extrapolated using the estimated pharmacokinetic parameters. With exposure to chloroform, the fraction of the elimination amount at 1 ppb exposure (low concentration) against the exposure concentration was estimated to be 1.1 times higher than the fraction at 10 ppm exposure (high concentration). With exposure to low concentrations (1 ppb), extrapolation showed that more chloroform (0.33 nmol/h/kg) was absorbed by the rats than chlorodibromomethane (0.11 nmol/h/kg), bromodichloromethane (0.072 nmol/h/kg), and carbon tetrachloride (0.053 nmol/h/kg). Our findings revealed differences in the absorption amounts among the substances for the same exposure concentrations.