A comparative study of the pharmacokinetics of carbon tetrachloride in the rat following repeated inhalation exposures of 8 and 11.5 hr/day.

To evaluate whether exposure to inhaled vapors for periods longer than 8 hr/day could affect the rates and routes of elimination, male Sprague-Dawley rats were repeatedly exposed to 100 ppm of radiolabeled carbon tetrachloride (14CCl4) in a closed-loop chamber. One group was exposed for 8 hr/day for 5 days and another group for 11.5 hr/day for 4 days. Two other groups were exposed for either 8 hr/day for 10 of 12 consecutive days or 11.5 hr/day for 7 of 10 days. The elimination of 14C activity was measured in the expired air, urine, and feces for up to 100 hr following exposure and the pharmacokinetic parameters were determined. Following 2 weeks of exposure to the 8-hr/day schedule, 14CCl4 in the breath and 14C activity in the feces comprised 45 and 48% of the total 14C excreted, respectively. Following 2 weeks of exposure to the 11.5-hr/day schedule, the values were 32 and 62%, respectively, indicating that repeated exposure to the longer schedule altered the route of elimination of CCl4. Regardless of the period of exposure, less than 8% of the inhaled 14CCl4 was excreted in the urine and less than 2% was exhaled in the breath as the 14CO2 metabolite. Approximately 97-98% of the 14C activity in the expired air was 14CCl4. The quantities of 14C noted in the feces and urine suggest that more than 60% of the inhaled CCl4 was metabolized. Elimination of 14CCl4 and 14CO2 in the breath followed a two-compartment, first-order pharmacokinetic model (r2 = 0.98). For rats exposed 8 hr/day and 11.5 hr/day for 2 weeks, the average half-lives for elimination of 14CCl4 in the breath for the fast (alpha) and slow (beta) phases averaged 96 and 455 min, and 89 and 568 min, respectively. The average alpha and beta half-lives for elimination of 14CO2 in the breath of rats exposed to the 11.5-hr/day schedule were 455 and 1824 min, and these were significantly longer than for the 8-hr/day groups, 305 and 829 min. The longer half-lives of elimination for 14CO2 and 14CCl4 which were observed for the groups exposed to the 11.5-hr/day schedule suggest that the 3.5 additional hr of daily exposure places a relatively greater percentage of the absorbed dose into poorly perfused lipophilic depots such as the fat.(ABSTRACT TRUNCATED AT 400 WORDS)