Dempster A M, Evans H L, Snyder C A
Toxicol Appl Pharmacol. 1984 Oct;76(1):195-203. doi: 10.1016/0041-008x(84)90042-5.
The time-effect relationship of the behavioral and hematological changes caused by inhaled benzene was investigated in C57BL mice. Mice were exposed to air, or 100, 300, 1000, or 3000 ppm benzene in standard inhalation chambers employing dynamic vapor exposure techniques. Mice were exposed for 6 hr/day for the number of days necessary to achieve a minimum concentration X time (Ct) product of 3000 ppm-days. The intermittent exposure regimen of 6 hr/day was employed to simulate occupational exposure. The most sensitive behavioral index (milk-licking) was affected by the lowest concentration tested (100 ppm), while homecage food intake, hindlimb grip strength, and body weight were reduced only at 1000 and 3000 ppm. Some of these previously undocumented behavioral changes occurred as rapidly as hematological changes that have been considered hallmarks of benzene toxicity. A significant decrease in circulating lymphocytes occurred after exposure to all concentrations. Circulating red blood cells were variably affected by benzene, in that anemia resulted after 10 days exposure to 100 ppm and after 3 days exposure to 300 ppm but not after 3 days exposure to 1000 ppm or a single exposure of 3000 ppm. The data indicate a departure from Ct relationships, and suggest that exposure duration as well as daily dose may be an important factor in benzene toxicity.
在C57BL小鼠中研究了吸入苯引起的行为和血液学变化的时间效应关系。采用动态蒸汽暴露技术，将小鼠置于标准吸入舱中，分别暴露于空气、100、300、1000或3000 ppm的苯环境中。小鼠每天暴露6小时，持续一定天数，以达到最低浓度×时间（Ct）乘积为3000 ppm - 天。采用每天6小时的间歇暴露方案来模拟职业暴露。最敏感的行为指标（舔乳）受到测试的最低浓度（100 ppm）的影响，而笼内食物摄入量、后肢握力和体重仅在1000和3000 ppm时降低。这些以前未记录的行为变化中的一些与被认为是苯毒性标志的血液学变化一样迅速出现。暴露于所有浓度后，循环淋巴细胞均显著减少。循环红细胞受苯的影响各不相同，即暴露于100 ppm 10天后和暴露于300 ppm 3天后出现贫血，但暴露于1000 ppm 3天后或单次暴露于3000 ppm后未出现贫血。数据表明偏离了Ct关系，并表明暴露持续时间以及每日剂量可能是苯毒性的一个重要因素。
