IN-VIVO EVALUATION OF CHEMICAL BIOPERSISTENCE OF NONFIBROUS INORGANICPARTICLES

The lung's response to deposited particles may depend upon the physica l-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 re gions of the lung. Depending on the animal species studied, particle t ype, and particle load, inorganic materials are ingested by macrophage s 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 m echanism 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 li ning layer, airway mucus, or interstitial fluid. However, many particl es such as cobalt oxide or iron oxide which dissolve very little in si mulated lung fluid, are solubilized more rapidly within alveolar macro phages. Clearance of particles from the lungs can be followed by a num ber of techniques, both invasive and noninvasive. The approaches vary in expense and resolution, and can be directed toward quantifying mech anical removal of particles versus their intracellular dissolution. No ninvasive methods permit repeated measurements of particle retention i n the lungs of the same animal or human and thus allow replications an d serial measurements. Greater precision with respect to the sites of retention and redistribution is achieved with quantitative morphometri c methods that utilize fixation followed by physically dividing the re spiratory tract into individual pieces. Microwave drying or slam-freez ing can eliminate the possibility of significant particle redistributi on or loss of particles and dissolved elements during tissue processin g. Detection of particles and therefore evidence of clearance can rely upon any distinctive property of the aerosol. Particles may be radioa ctive, fluorescent, or magnetic, or may have a characteristic Visual a ppearance. Detection techniques include radiography, analyses of radio activity, magnetometry, and microscopic approaches such as fluorescenc e and confocal microscopy, X-ray emission analysis, and electron energ y loss spectrometry (EELS). Using these approaches. considerable evide nce has been accumulated to conclude that particle dissolution in situ within alveolar macrophages and subsequent absorption by the circulat ion, rather than bulk transport, is the dominant mechanism for the lon g-term clearance of many insoluble minerals from the lungs.