2-PHASE PULMONARY CLEARANCE OF INSOLUBLE PARTICLES IN MAMMALIAN-SPECIES

Existing experimental data on pulmonary clearance of low-toxicity, poo rly soluble particles in several mammalian species including the rat, mouse, guinea pig, dog, monkey, and human have been analyzed using a t wo-exponential time-decay function with one exponential representing t he fast clearance phase and the other for the slow clearance phase. Ma ss fractions of both clearance phases and the corresponding clearance rates were determined from the lung burden data for different specific initial lung burdens (initial lung burden/lung weight). It was found that the slow clearance mass fraction increased with lung burden for a ll species, and it approached almost 100% when the specific initial lu ng burden exceeded 1 mg/g lung. However, the slow clearance mass fract ion at low lung burdens was found to be much higher for the slow-clear ing species (guinea pig, dog, monkey, and human) than far the fast-cle aring species (rat and mouse). It was also found that the fast clearan ce rate was nearly a constant, but the slow clearance rate decreased w ith lung burden. In addition, both clearance rates differed slightly b etween the fast-clearing and slow-clearing species. Based upon these d ata, a formula is proposed to calculate the clearance rate at any lung burden for humans.