The pharmacokinetics of inhaled chlorobenzene in the rat

Male rats were exposed for 8 hr/day to 100, 400, or 700 ppm of [14C]chlorobenzene vapor for either 1 or 5 days for the purpose of examining the dose dependency of parameters indicative of the toxicity process and the effect of repeated exposure. 14C burdens in the blood, liver, kidneys, lungs, and fat were measured at 0, 16, and 48 hr after exposure. The labeled material excreted in the urine and expired air was collected for 48 hr. Analysis was performed on both the rats and total amounts eliminated. The mercapturic acid percentage of the urinary metabolites excreted in the first 24 hr was measured. The 14C burdens of all tissues increased in proportion to increased exposure concentrations, except for adipose tissue burdens, which increased more than 30-fold between 100 and 700 ppm. Respiratory elimination of 14C also increased disproportionately. The urinary metabolite profile was altered, with a dose-dependent decreased in the mercapturic acid percentage from 68% at 100 ppm to 51% at 700 ppm. Changes due to multiple versus single exposures were higher tissue burdens 48 hr after exposure, less total excretion of label, a lesser percentage of the total excreted through respiration, and a change in the rate of respiratory excretion. The dose-dependent changes are postulated to be due to saturation of the metabolic elimination of chlorobenzene. The effect of multiple exposure is apparently some stimulation of metabolism.