THE ROLE OF CLEARANCE AND DISSOLUTION IN DETERMINING THE DURABILITY OR BIOPERSISTENCE OF MINERAL FIBERS

It is generally accepted that to cause pulmonary disease, mineral fibe rs must be relatively long and thin but also able to remain in the lun g for long periods. This ''biopersistence'' of fibers is limited by tw o main mechanisms of fiber clearance. removal by macrophages after pha gocytosis and, for some fibers, by actual dissolution. The relative im portance of these mechanisms has not been properly evaluated for any t ype of fiber and wilt certainly vary with mineral type. The efficiency of macrophage clearance is greatest with short fibers (<5 mu m long) and is reduced as fibers get longer. Fibers >50 mu m long cannot be cl eared by macrophages and for some mineral types they may remain in the lung permanently. Others may fracture into shorter lengths, perhaps a ided by chemical dissolution, and thus become susceptible to macrophag e clearance. However, for a number of areas relating to fiber removal from the lung parenchyma detailed information is still needed. Do dust s differ in their ability to attract macrophages and stimulate these c ells to phagocytosis? Following dust uptake what controls the movement of macrophages? Some may penetrate to the interstitium, some phagocyt osing fibers in interstitial sites may migrate back to the alveolar sp ace. Some move to the mucociliary escalator and some to the lymphatics . Some, most importantly, move to the pleura. Fibers are found and pha gocytosed in the interstitium during the early stages of disease devel opment, but with time many fibers appear isolated in areas of fibrous tissue. Are such fibers subsequently ignored or can they reenter the d isease process after years of isolation? Finally, can phagocytosis by macrophages effect dissolution of fibers? The pH of the macrophage pha golysosome system is acid, while tissue fluids are close to neutral. S ome fiber formulations might dissolve faster in an acid environment wh ile some might be more stable.