Interspecies Comparison of Lung Clearance of "Insoluble" Particles

Abstract

Lung clearance studies after the inhalation of monodisperse, radiolabelled test particles including lung retention measurements and excretion analysis allow for estimates of the kinetics of long-term particle transport out of the thorax into the gastro-intestinal tract. Data of several interspecies comparisons using either radiolabelled fused aluminosilicate particles or 57C03O4 particles were reviewed and compared. Species included were: man, baboon, beagle dog, guinea pig, HMT rat, F-344 rat, Long-Evans rat, hamster, mouse.Particle transport M(t) after the first days after inhalation is a slow clearance mechanism which is independent of the particle material and size used (0.5 -4 (im geom. diameter). M(t) was reproducible in the experimental species studied. In man, baboon, and dog the initial daily fraction Mo of the contemporary lung burden transported out of the thorax is 0.001 d~1 which is an order of magnitude less than the initial rates in rodents. Particle transport rate decreases rapidly from its initial value in all species studied. The decay of particle transport varies considerably between the species and strains. The half-life of the decreasing transport rate is slower in man, dog, F-344 rat, hamster and mouse (100 -200 days) than in baboon, HMT rat and Long-Evans rat (< 50 days). From these studies estimates of lung retention during chronic aerosol exposure showed no equilibrium value indicating that long-term particle transport is not a sufficiently effective clearance mechanism to keep the lung burden from continuousy increasing during chronic exposure.

Morphological aspects of particle uptake by lung phagocytes

“…Not only the phagocytic activity but also the migration of macrophages-both of which are essential for the effective clearance of particles-have been shown to differ between species (phagocytic activity: hamster Ͼ rat Ͼ guinea pig Ͼ mouse; migration: rat Ͼ mouse Ͼ hamster Ͼ guinea pig [Warheit and Hartsky, 1993]). Humans have the slowest and rats the most rapid particle-clearing rates (Bailey et al, 1989;Kreyling 1990;Philipson et al, 1996). Figures 5 and 6 represent different types of particles taken up by airway and alveolar macrophages less than an hour after the onset of inhalation.…”

Intracellular Particle Dissolution in Alveolar Macrophages

“…Although translocation is assumed to be similar in each compartment of the respiratory tract, the effectiveness ofparticle transport mechanisms varies considerably between extrathoracic airways, the tracheobronchial tree, and the alveolar region. Because particle transport from the alveolar region is slow, particularly in man (11), translocation of material from particles retained in the structures ofthe gas exchange region is recognized to be a very important clearance mechanism for the lung parenchyma. Moreover, recent studies have indicated that aerosol particles that were believed to be insoluble gradually dissolve in the lungs (12)(13)(14).…”

Pulmonary Alveolar Phospholipoproteinosis Induced by Orasol Navy Blue Dust

“…Alveolar lesions were seen in 22 Lungs from rats having 20 exposures showed morphologically similar lesions of focal mononuclear cell aggregates with alveolar debris. They were smaller in size than seen in the 100 exposures group and present at a lower incidence, occurring in six of the ten rats receiving 20 exposures.…”