In vivo evaluation of chemical biopersistence of nonfibrous inorganic particles.

Abstract

The lung's response to deposited particles may depend upon the physical-chemical properties of the particles, the amount initially deposited, and the persistence of the particles. Clearance involves mucociliary transport as well as the action of phagocytic cells in nonciliated regions of the lung. Depending on the animal species studied, particle type, and particle load, inorganic materials are ingested by macrophages on alveolar surfaces with half-times of 0.6 to 7 hr. Particle-laden macrophages may migrate to airways, but we believe that an important mechanism of clearance is the dissolution of particles within alveolar macrophages and the subsequent translocation of dissolved materials to the blood. Particle dissolution in situ has long been recognized but was often thought to be carried out extracellularly in the alveolar lining layer, airway mucus, or interstitial fluid. However, many particles such as cobalt oxide or iron oxide which dissolve very little in simulated lung fluid, are solubilized more rapidly within alveolar macrophages. Clearance of particles from the lungs can be followed by a number of techniques, both invasive and noninvasive. The approaches vary in expense and resolution, and can be directed toward quantifying mechanical removal of particles versus their intracellular dissolution. Noninvasive methods permit repeated measurements of particle retention in the lungs of the same animal or human and thus allow replications and serial measurements. Greater precision with respect to the sites of retention and redistribution is achieved with quantitative morphometric methods that utilize fixation followed by physically dividing the respiratory tract into individual pieces. Microwave drying or slam-freezing can eliminate the possibility of significant particle redistribution or loss of particles and dissolved elements during tissue processing. Detection of particles and therefore evidence of clearance can rely upon any distinctive property of the aerosol. Particles may be radioactive, fluorescent, or magnetic, or may have a characteristic visual appearance. Detection techniques include radiography, analyses of radioactivity, magnetometry, and microscopic approaches such as fluorescence and confocal microscopy, X-ray emission analysis, and electron energy loss spectrometry (EELS). Using these approaches, considerable evidence has been accumulated to conclude that particle dissolution in situ within alveolar macrophages and subsequent absorption by the circulation, rather than bulk transport, is the dominant mechanism for the long-term clearance of many insoluble minerals from the lungs.