Evaluation of the Biopersistence of Commercial and Experimental Fibers Following Inhalation

Abstract

The biopersistence of three fibers was evaluated using an inhalation model. The fibers studied were man-made vitreous fiber (MMVF) 11, a commercially produced glass fiber; Fiber B, a relatively soluble glass fiber; and Fiber J, a synthetic stonewool with a high content of alkaline earth oxides. Fischer 344 male rats were exposed to a well-defined rat respirable aerosol (mean diameter of ≤1 μm) at a target concentration of 30 mg/m³, 6 h/day for 5 days. Following the end of the exposure period, subgroups were sacrificed at 1 h, 1 day, 5 days, 4 wk, 13 wk, 26 wk, and 52 wk. At sacrifice, the whole lung was removed, weighed, and immediately 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 3 fibers were found to have similar lung burdens ranging from 7.36-7.72 × 10⁶ fibers/lung with geometric mean diameters of 0.42-0.54 μm. The three fibers were found to be removed from the lung following the cessation of inhalation exposure with half-lives of 8-42 days, in addition, an important difference in removal was seen between the long fiber (>15 μm) and short fiber (<15 μm) fractions. The long fibers cleared more rapidly with a T_ψ. of 20, 5, and 7 days for MMVF 11, Fiber B, and Fiber J, respectively. The dissolution of the long fibers appeared to result in rapid breaking and disintegration with the formation of short fibers and particles within the first 24 h. The short fiber fraction had a longer Y_ψ of 46, 10, and 12 days for MMVF 11, Fiber B, and Fiber J, respectively. Short fibers have been reported to be phagocytized by macrophages and either cleared by ciliated mucous transport or eventually translocated to the bronchial-associated lymphoid tissue and lymph nodes. The pH of the phagolysosome within the macrophage has been reported to be <5. Acellular in vitro studies indicate a slower dissolution at this pH. The diameters of either the long or short fibers did not change significantly over time, supporting the in vitro observation of the formation of a leached layer with similar physical dimensions as the original fiber. The clearance half-times for the three fibers evaluated were considerably shorter than that reported for crocidolite asbestos, a known fiber carcinogen, suggesting that these fibers would not persist in the lung as has been shown to be in the case for crocidolite. These results demonstrate that the inhalation biopersistence model provides a sensitive means of evaluating the critical parameters of fiber biodurability and clearance in the lung. For the MMVF fibers tested, the longer fibers not only dissolve but also appear to break apart in the lung, thereby quickly removing the potentially carcinogenic fraction from the lung.