Placke M E, Griffis L, Bird M, Bus J, Persing R L, Cox L A
Chevron Research and Technology Co., Richmond, CA, USA.
Toxicology. 1996 Oct 28;113(1-3):253-62. doi: 10.1016/0300-483x(96)03454-3.
The oncogenic potential of isoprene as affected by concentration, length of daily exposure, and weeks of exposure over the life-span of the animal, as independent variables, was evaluated. Ten groups were exposed for 8 h/day, 5 days/week as follows (ppm-weeks): 0-80, 10-80, 70-40, 70-80, 140-40, 280-20, 280-80, 700-80, 2200-40, 2200-80. Two groups were exposed for 4 h/day: 2200-20, 2200-80. Groups were held until 96 or 105 weeks on study. The concentration x time (duration of exposure) values provided a series of theoretically equivalent exposure hazards. There was an exposure-related increased incidence of liver, lung, Harderian gland and forestomach tumors, and hemangiosarcomas and histiocytic sarcomas. The LOEL appeared to be 70 ppm. These results are similar to the profile of tumors seen in 1,3-butadiene (BD)-exposed mice without the early onset of T-cell lymphoma as seen with BD. Isoprene appears to be about one order of magnitude less potent than BD in mice. Statistical analyses indicated that the product of isoprene concentration, and length/duration of exposure was not a sufficient basis for predicting tumor risk at any site. Extrapolation of tumor probability between the high and low doses based on cumulative exposure was not appropriate and could not be justified by statistical models. A threshold effect level and strong nonlinearities with respect to concentration appeared to exist for tumor development in this study.
评估了作为自变量的异戊二烯的致癌潜力，其受浓度、每日暴露时长以及动物寿命期内的暴露周数影响。十组动物每天暴露8小时，每周暴露5天，具体如下（ppm-周）：0 - 80、10 - 80、70 - 40、70 - 80、140 - 40、280 - 20、280 - 80、700 - 80、2200 - 40、2200 - 80。两组动物每天暴露4小时：2200 - 20、2200 - 80。各实验组持续观察至96周或105周。浓度×时间（暴露持续时间）值提供了一系列理论上等效的暴露风险。出现了与暴露相关的肝脏、肺、哈德氏腺和前胃肿瘤以及血管肉瘤和组织细胞肉瘤的发病率增加。最低观察到有害作用的水平（LOEL）似乎为70 ppm。这些结果与在暴露于1,3 - 丁二烯（BD）的小鼠中看到的肿瘤情况相似，但没有BD暴露小鼠中出现的早期T细胞淋巴瘤。在小鼠中，异戊二烯的效力似乎比BD低约一个数量级。统计分析表明，异戊二烯浓度与暴露时长的乘积不是预测任何部位肿瘤风险的充分依据。基于累积暴露在高剂量和低剂量之间推断肿瘤概率是不合适的，并且无法通过统计模型证明其合理性。在本研究中，肿瘤发生似乎存在阈值效应水平以及相对于浓度的强烈非线性关系。
