A study on the distribution of methylchloroform and n-octane in the mouse during and after inhalation.

Abstract

Distribution of methylchloroform and n-octane, respectively, in the blood, liver, kidney and brain of mice was studied at different inspired air concentrations and after different exposure times. The air concentration varied between 10-10,000 ppm; and the exposure time, between 0.5-24 h. The resulting solvent concentrations in kidney and brain were about the same, but liver concentrations were usually somewhat higher for both solvents. There was a linear dependence between inspired air concentration and tissue concentrations at fixed exposure times. A correlation between blood and organ concentrations was observed in animals exposed at different inhalation air concentrations but not in animals exposed only at one fixed concentration. Ratios between the concentrations of the solvents in the organs and blood were higher for n-octane than for methylchloroform. The ratios increased as the exposure concentration increased for all organs studied in the case of n-octane but only for the liver in the case of methylchloroform. When the exposure dose, i.e., inspired air concentration .times. time, was generated in different ways, a high concentration during a short exposure resulted in a 10 times higher organ concentration than a low concentration during a long exposure. Liver, kidney and brain concentrations generally did not differ more than twice between methylchloroform and n-octane after exposure of the same concentration and duration. The blood concentration, however, was much less in n-octane exposed animals than in methylchloroform exposed ones. A pharmacokinetic model with both uptake and elimination of the first order fitted the empirical data better for methylchloroform than a model with zero order uptake and first order elimination. Postexposure concentrations of methylchloroform were linear in a semilog graph. A 1-compartment pharmacokinetic model was in accordance with the experimental data for methylchloroform. For n-octane, however, at least a 2-compartment model must be assumed.