Concentration-response relationships of rat lungs to exposure to oxidant air pollutants: a critical test of Haber's Law for ozone and nitrogen dioxide.
Concentration-response relationships of rat lungs to exposure to oxidant air pollutants: a critical test of Haber's Law for ozone and nitrogen dioxide.
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大鼠肺暴露于氧化剂空气污染物的浓度响应关系：对臭氧和二氧化氮哈伯定律的关键测试。
DOI：
10.1016/0041-008x(92)90281-v
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发表时间：
1992
影响因子：
3.8
通讯作者：
Last,JA
中科院分区：
文献类型：
--
作者：
Gelzleichter,TR;Witschi,H;Last,JA
暴露协议的目的是询问是否肺损伤大鼠暴露于臭氧或二氧化氮是成比例的剂量率或累积剂量。因此，大鼠对氧化剂空气污染物浓度和暴露时间（C × T）的恒定乘积的反应进行了评估，暴露时间为每天6-24小时，暴露时间为臭氧（0.2-0.8 ppm）或二氧化氮（3.6-14.4 ppm）浓度的四倍范围，为期3天。通过肺灌洗液上清液中总蛋白含量的变化或通过肺灌洗液颗粒中特定细胞类型含量的变化来定量大鼠肺的反应。这些实验的结果清楚地表明，急性肺损伤是三个最高剂量率的累积剂量（即C × T乘积）的函数。然而，当暴露持续时间延长到包括整个24小时期间（测试的最低剂量率）时，肺部反应明显减弱。大鼠也暴露于臭氧和二氧化氮的混合物中，C × T乘积保持不变。我们的研究结果清楚地表明，当大鼠暴露于臭氧和二氧化氮的组合，肺损伤是峰值浓度的函数，而不是累积剂量的函数。这种对哈伯定律的偏离归因于对氧化剂空气污染物的这种特定混合物的浓度依赖性、协同性（大于加和性）响应。
Exposure protocols were designed to ask whether lung damage in rats exposed to either ozone or nitrogen dioxide is proportional to dose rate or to cumulative dose. Thus, the response of rats to a constant product of concentration of oxidant air pollutant and time of exposure (C × T) was evaluated for 3-day exposures over a fourfold range of concentrations of ozone (0.2–0.8 ppm) or of nitrogen dioxide (3.6–14.4 ppm) for exposure durations of 6–24 hr per day. The response of rat lungs was quantified by changes in total protein content of lung lavage supernatants or by changes in content of specific cell types in lung lavage pellets. The results of these experiments clearly demonstrate that acute lung damage is a function of cumulative dose (that is, C × T product) for the three highest dose rates tested. However, when exposure duration is extended to include the entire 24-hr period (the lowest dose rate tested), there is a marked attenuation of pulmonary response. Rats were also exposed to mixtures of ozone and nitrogen dioxide with the C × T product held constant. Our results clearly demonstrate that when rats are exposed to combinations of ozone and nitrogen dioxide, lung damage is a function of peak concentration rather than a function of cumulative dose. This deviation from Haber's Law is attributed to a concentration-dependent, synergistic (greater than additive) response to this specific mixture of oxidant air pollutants.