Dissolution of Glass Fibers in the Rat Lung Following Intratracheal Instillation

Abstract

The biopersistence of airborne fibers is felt to play an important role in their potential toxicity. Since the dissolution rate of fibers can be measured in cell-free systems, the current study was undertaken to determine if the dissolution rate of fibers in the lung was related to the dissolution rate of fibers in vitro, and whether dissolution serves to remove fibers from the lung. To determine dissolution rates in vivo, suspensions of fibers were administered to rats by intratracheal instillation, and the numbers, lengths, and diameters of fibers recovered from the lungs at intervals up to 1 yr after administration were measured by phase-contrast optical microscopy. Five different glass fibers were used that had dissolution rates ranging from 2 to 600 ng/cm²/h measured in vitro in simulated lung fluid at pH 7.4. Examination of the diameter distributions of fibers longer than 20 μm showed that the peak diameter decreased steadily with time after instillation, at the same rate measured for each fiber in vitro, until it approached zero. Measurements of the total number of fibers remaining in the rats' lungs at times up to 1 yr after instillation suggest that not many of the administered fibers were being cleared by macrophage-mediated transport via the conducting airways. A computer simulation of the fibers in the lungs was performed in which each of the administered long fibers (20 μm or longer) was decreased in diameter according to the rate measured in vitro, while the short fibers (less than 20 μm long) were unaffected. The ratio of long to short fibers predicted by this simulation agreed well with this quantity measured from the fibers recovered from the rats' lungs at each time interval after instillation. It was concluded that long glass fibers, at least those longer than 20 μm, are removed from the lung by dissolution at much the same rate measured in vitro.