Evaluation of Soluble fibers Using the Inhalation Biopersistence Model, a Nine-fiber Comparison

Abstract

The biopersistence of nine fibers was evaluated using an inhalation model. The fibers studied were compositions with different in vitro acellular solubility. The commercial and new glass wool fibers were essentially sodium borosilicates and the commercial and new stone wools were essentially calcium modified silicates. Fischer 344 male rats were exposed to a well-defined rat respirable aerosol (mean diameter of ∼1 μm) 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. At sacrifice, the whole lung was removed, weighed, and frozen at -20°C for subsequent digestion by low-temperature plasma ashing. The number and bivariate size distribution of the fibers in the aerosol and lung were determined. At 1 h following the last exposure, the 9 fibers were found to have lung burdens ranging from 7.4 to 33 ° 10⁶ fibers/lung with geometric mean diameters (CMD) of 0.40–0.54 μm. The range of initial lung burdens was found to reflect the different bivariate distributions in the exposure aerosol. The fibers were found to be removed from the lung following the cessation of exposure with weighted half-lives of WHO fibers ranging from 11 to 54 days. The WHO clearance was found to closely reflect the clearance of fibers in the 5–20 μm length range. An important difference in removal was seen between the long fiber (L > 20 μm) and shorter fiber (L between 5 and 20 μm and L < 5 μm) fractions depending upon composition. For all glass wools and the new stone wools, the longer fibers were removed notably faster than the shorter fibers. It was found that the time for complete fiber dissolution based on the acellular in vitro dissolution rate at pH 7.4 was highly correlated (r = .97, p < .01) with the clearance half-times of fibers > 20 μm in length when using a double exponential fit to the data. No such correlations were found with any of the length fractions using the acellular in vitro dissolution rate at pH 4.5. Examination of the fiber length distribution and particles in the lung from 1 h through 5 days of exposure indicated that, especially for those fibers that form leached layers, a certain amount of fiber breakage may have occurred during this early period. These results demonstrate that the inhalation biopersistence model can be used in the process of evaluating the optimal composition for the reduction of fiber biodurability in the lung, and that for fibers with high acellular solubility at pH 7.4, the clearance of long fibers is very rapid.