Investigation of the critical amounts of inhaled particles in rat lung as a cause of fibrosis

作业环境中可吸入颗粒物对人体健康的不良影响主要取决于肺内颗粒物的数量和生物持久性。从啮齿类动物的研究结果来看，肺中纤维含量超过临界值(约1 mg/只肺)会导致生物持久性和纤维化改变的延长。为了阐明肺中纤维的临界含量，用辛酸钾晶须通过气管内滴注法和吸入法研究了肺内颗粒物数量与生物持久性和病理变化的定量关系。气管内滴注法分别向大鼠肺内注入0.5、1.0、2.0、5.0 mg的晶须。随着肺内染毒剂量的增加，生物耐受性延长，病理改变加重。然而，在定量关系上观察到滴注结果和吸入结果之间的差异。然后在4周内进行高浓度吸入试验。肺部给药剂量为1.5 mg，几乎是前人研究的临界量，但未观察到生物耐受性的延长。为了明确临界量，当沉积量在1或2 mg左右时，需要对具有不同物理化学性质的纤维进行更多的吸入实验，并考察了颗粒形状对不良健康影响的影响。将2 mg辛酸钾颗粒滴入大鼠肺内，并与胡须试验结果进行比较。与胡须相比，颗粒清除更快，病变更小。这一结果表明，颗粒物的形状是有害健康影响的重要指标。

The adverse health effect of respirable particles in working environment is thought to depend on the amounts and biopersistence of particles in lung. From the results of our rodent research, fiber amounts in lung over the critical amount (about 1 mg per lung) caused the prolongation of the biopersistence and fibrotic change.For the clarification of the critical amounts of fiber in lung, the quantitative relationship between particle amount in lung and biopersistence and pathological change were investigated using potassium octatitanate whisker by intratracheal instillation method and inhalation method. In intratracheal instillation method, 0.5, 1.0, 2.0, 5.0 mg of whisker were instilled to rat lungs. The biopersistence became longer and the pathological change became severe as the dose in lung increased. However the discrepancy between instillation results and inhalation results in the quantitative relation was observed. Then inhalation research in high concentration during 4 week was performed. The amount in lung was 1.5 mg which is almost critical amount in previous research but the prolongation in bioresistence was not observed. In order to clarify the critical amount, we need to conduct more inhalation experiments using fibers which have different physicochemical properties when the deposited amount is around 1 or 2 mg.furthermore the effect of particle shape on the adverse health effect was investigated. 2 mg of potassium octatitanate particle was instilled to rat lung and compared with the results of whisker. Particle was cleared faster and smaller pathological change than whisker. This results suggest that the particle shape is important index for adverse health effect.