TWO-PHASE PULMONARY CLEARANCE OF INSOLUBLE PARTICLES IN MAMMALIAN SPECIES

Abstract

Existing experimental data on pulmonary clearance of low-toxicity, poorly soluble particles in several mammalian species including the rat, mouse, guinea pig, dog, monkey, and human have been analyzed using a two-exponential time-decay function with one exponential representing the fast clearance phase and the other for the slow clearance phase. Mass 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 all species, and it approached almost 100% when the specific initial lung burden exceeded 1 mg/ g lung. However, the slow clearance mass fraction at low lung burdens was found to be much higher for the slow-clearing species (guinea pig, dog, monkey, and human) than for the fast-clearing species (rat and mouse). It was also found that the fast clearance rate was nearly a constant, but the slow clearance rate decreased with lung burden. In addition, both clearance rates differed slightly between the fast-clearing and slow-clearing species. Based upon these data, a formula is proposed to calculate the clearance rate at any lung burden for humans.