COMPARISON OF THE CHEMICAL EVOLUTION OF MMVF FOLLOWING INHALATION EXPOSURE IN RATS AND ACELLULAR IN VITRO DISSOLUTION

Abstract

In the process of developing new fibers or evaluating existing fibers, the dissolution coefficient is often determined using an acellular in vitro assay. This coefficient has been found useful in selecting fibers based on solubility and has been shown to be related to the clearance half-time of long fibers (>20 m) following inhalation in rats. The chemical evolution of fibers following in vitro dissolution and inhalation was examined to evaluate the comparability of these two methods. The fibers studied ranged from compositions similar to commercial insulation materials to new glasses and stone wools that have been developed for enhanced solubility. The inhalation studies were performed using Fischer 344 male rats exposed to a well-defined rat respirable aerosol (mean diameter of 1 m) at a concentration of 30 mg/m3, 6 h/day for 5 days, with postexposure sacrifices at 1 h, 1 day, 5 days, 4 wk, 13 wk, and 26 wk. The in vivo results reported have been from fibers recovered from the lung that were primarily less than 20 m in length. The in vitro dissolution measurements were performed using a continuous-flow model with simulated lung fluid based upon a modified Gamble's media using either 1- or 10- m-diameter fibers without discrimination of length. The inhalation studies show that the composition of many of the fibers recovered from the lung changes with time in the lungs, with a depletion in Na O2, CaO, and MgO and a relative enrichment in SiO2 and Al2O3, with this evolution strongly depending upon glass composition. B2O3 has been found (on 10- m-diameter fibers in vitro as analyzed by secondary ion mass spectrometry) to also be depleted. The chemical evolution of these shorter fibers (L < 20 m) is consistent with that obtained from the in vitro experiments at pH 7.4, although the rate of variation observed with the two methods varied. These results clearly demonstrate that those fibers whose composition changes quickly during in vivo studies are the same as those whose composition changes quickly during in vitro assays. These studies demonstrate that the chemical evolution of the shorter fibers recovered following in vivo inhalation studies mirrors closely the changes found from the in vitro assays. These results complement those already reported for fibers longer than 20 m, which have been shown to be removed from the lung primarily by dissolution. </abs>