Yu R C, Rappaport S M
Department of Environmental Science and Engineering, University of North Carolina, Chapel Hill 27599-7400, USA.
Occup Environ Med. 1996 Aug;53(8):567-72. doi: 10.1136/oem.53.8.567.
To test the validity of a Michaelis-Menten-like kinetic model of pulmonary clearance of insoluble dusts.
Data were investigated from studies of pulmonary clearance in F344 rats exposed to antimony trioxide (Sb2O3), photocopy test toner, polyvinyl chloride powder (PVC), and diesel exhaust particles. The Michaelis-Menten-like model was used to develop a relation in which the pulmonary clearance half time was a linear function of lung burden. After combining all data, linear regression techniques were applied to investigate the underlying relations. With the estimated intercepts and slopes, the Michaelis-Menten-like kinetic parameters kmax (maximal clearance rate) and m1/2 (a characteristic lung burden at which kmax is reduced by 50%) were derived for the four dusts.
The experimental data fit the linear regression very well (R2 = 0.989), suggesting that pulmonary clearance for the four dusts followed Michaelis-Menten-like kinetics. Values of the intercept terms were not significantly different among the four dusts (P = 0.294), indicating that the intrinsic clearance rates of F344 rats were the same among the four experiments. The intrinsic clearance half time was estimated to be 77.8 days, leading to an estimated kmax of 0.0089 day-1. However, the slopes of the linear relations were significantly different among the four dusts (P < 0.001). Values of m1/2 were ranked in the order of: Sb2O3 (0.69 mg) < photocopy test toner (0.97 mg) < diesel exhaust (2.49 mg) congruent to PVC (2.90 mg).
This study suggests that the Michaelis-Menten-like kinetic model reasonably describes the kinetic behavior of pulmonary clearance in F344 rats. The parameters m1/2 can be used to differentiate the potency of a particular dust for impairing pulmonary clearance.
检验一种类似米氏动力学模型用于不溶性粉尘肺清除的有效性。
对暴露于三氧化二锑（Sb2O3）、复印机测试碳粉、聚氯乙烯粉末（PVC）和柴油机尾气颗粒的F344大鼠肺清除研究的数据进行调查。使用类似米氏模型建立一种关系，其中肺清除半衰期是肺负荷的线性函数。合并所有数据后，应用线性回归技术研究潜在关系。根据估计的截距和斜率，得出四种粉尘的类似米氏动力学参数kmax（最大清除率）和m1/2（使kmax降低50%时的特征性肺负荷）。
实验数据与线性回归拟合良好（R2 = 0.989），表明四种粉尘的肺清除遵循类似米氏动力学。四种粉尘的截距项值无显著差异（P = 0.294），表明在四个实验中F344大鼠的固有清除率相同。估计固有清除半衰期为77.8天，得出估计的kmax为0.0089天-1。然而，四种粉尘线性关系的斜率有显著差异（P < 0.001）。m1/2值的排序为：Sb2O3（0.69毫克）<复印机测试碳粉（0.97毫克）<柴油机尾气（2.49毫克）与PVC（2.90毫克）相当。
本研究表明类似米氏动力学模型合理地描述了F344大鼠肺清除的动力学行为。参数m1/2可用于区分特定粉尘损害肺清除的效力。
