Paustenbach D J, Carlson G P, Christian J E, Born G S
Fundam Appl Toxicol. 1986 Apr;6(3):484-97. doi: 10.1016/0272-0590(86)90222-8.
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)
为评估每天吸入蒸汽超过8小时是否会影响消除速率和消除途径，将雄性斯普拉格-道利大鼠置于闭环舱中，反复暴露于100 ppm放射性标记的四氯化碳（14CCl4）环境中。一组每天暴露8小时，持续5天；另一组每天暴露11.5小时，持续4天。另外两组分别连续12天中有10天每天暴露8小时，或10天中有7天每天暴露11.5小时。暴露后长达100小时内，在呼出气体、尿液和粪便中测量14C活性，并确定药代动力学参数。在每天暴露8小时的方案下暴露2周后，呼出气体中的14CCl4和粪便中的14C活性分别占总排泄14C的45%和48%。在每天暴露11.5小时的方案下暴露2周后，相应数值分别为32%和62%，这表明反复暴露于较长时间方案会改变CCl4的消除途径。无论暴露时间长短，吸入的14CCl4中经尿液排泄的不到8%，经呼出气体以14CO2代谢产物形式呼出的不到2%。呼出气体中约97 - 98%的14C活性是14CCl4。粪便和尿液中记录的14C量表明，吸入的CCl4超过60%被代谢。呼出气体中14CCl4和14CO2的消除符合二室一级药代动力学模型（r2 = 0.98）。对于每天暴露8小时和11.5小时达2周的大鼠，呼出气体中14CCl4消除的快相（α）和慢相（β）平均半衰期，8小时组分别为96分钟和455分钟，11.5小时组分别为89分钟和568分钟。每天暴露11.5小时组大鼠呼出气体中14CO2消除的平均α和β半衰期分别为455分钟和1824分钟，显著长于每天暴露8小时组的305分钟和829分钟。每天暴露11.5小时组观察到的14CO2和14CCl4较长消除半衰期表明，每天额外3.5小时的暴露使相对更大比例的吸收剂量进入灌注不良的亲脂性储存库，如脂肪中。（摘要截选至400字）
