Bolton R E, Vincent J H, Jones A D, Addison J, Beckett S T
Br J Ind Med. 1983 Aug;40(3):264-72. doi: 10.1136/oem.40.3.264.
Two types of experiments were carried out to examine the effects of deposition and clearance on the accumulation in the lungs of rats of inhaled fibres of UICC amosite. In the first experiment the mass lung burdens of the dust in question were measured as a function of the time at which animals were killed after the cessation of the six week exposure period, and in the second the masses were measured for rats removed from exposure and killed at intervals during the exposure period itself. The experimental conditions were chosen to complement those of earlier work. Taken together with the results of that earlier work, the new results provide the basis for a simple mathematical model of the kinetics of deposition and clearance which appears to account for the major observed trends. Most significantly, there is strong evidence for an overload of clearance at high lung burdens (exceeding about 1500 micrograms/rat), in which a breakdown occurs of the intermediate rate clearance mechanisms (time constants of the order of 12 days). This hypothesis is supported for inhaled asbestos dust, quartz dust, and diesel fume by results obtained elsewhere. Biological explanations for the clearance overload hypothesis are at present speculative, involving discussion of the role of the macrophage in pulmonary clearance. It is believed that the clearance overload hypothesis could have possible consequences for people occupationally exposed to airborne dusts.
进行了两类实验，以研究沉积和清除对大鼠肺部吸入的国际癌症研究机构（UICC）铁石棉纤维蓄积的影响。在第一个实验中，测量了在为期六周的暴露期结束后，动物被处死时肺部粉尘的质量负荷与时间的函数关系；在第二个实验中，测量了在暴露期内从暴露环境中取出并在不同时间间隔处死的大鼠肺部粉尘的质量。选择这些实验条件是为了补充早期研究的条件。结合早期研究的结果，新结果为沉积和清除动力学的简单数学模型提供了基础，该模型似乎可以解释观察到的主要趋势。最值得注意的是，有强有力的证据表明，在高肺负荷（超过约1500微克/只大鼠）时清除会出现过载，其中中间速率清除机制（时间常数约为12天）会发生故障。其他地方获得的结果支持了这一关于吸入石棉粉尘、石英粉尘和柴油烟雾的假设。目前，清除过载假设的生物学解释只是推测性的，涉及对巨噬细胞在肺部清除中的作用的讨论。人们认为，清除过载假设可能会对职业暴露于空气中粉尘的人产生潜在影响。
