EVALUATION OF THE BIOPERSISTENCE OF COMMERCIAL AND EXPERIMENTAL FIBERS FOLLOWING INHALATION

The biopersistence of three fibers was evaluated using an inhalation m odel. The fibers studied were man-made vitreous fiber (MMVF) 11, a com mercially produced glass fiber; Fiber B, a relatively soluble glass fi ber; and Fiber I, a synthetic stonewool with a high content of alkalin e earth oxides. Fischer 344 male rats were exposed to a well-defined r at respirable aerosol (mean diameter of less than or equal to 1 mu m) at a target concentration of 30 mg/m(3), 6 h/day for 5 days. Following the end of the exposure period, subgroups were sacrificed at 1 h, 1 d ay, 5 days, 4 wk, 13 wk, 26 wk, and 52 wk. At sacrifice, the whole lun g was removed, weighed, and immediately frozen at -20 degrees C for su bsequent digestion by low temperature plasma ashing. The number and bi variate size distribution of the fibers in the aerosol and lung were d etermined. At 1 h following the last exposure, the 3 fibers were found to have similar lung burdens ranging from 7.36-7.72 x 10(6) fibers/lo ng with geometric mean diameters of 0.42-0.54 mu m. The three fibers w ere found to be removed from the lung following the cessation of inhal ation exposure with half-lives of 8-42 days. In addition, an important difference in removal was seen between the long fiber (>15 mu m) and short fiber (>15 mu m) tractions. The long fibers cleared more rapidly with a T-1/2 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 lo nger T-1/2 of 46, 10, and 12 days for MMVF 11, Fiber B, and Fiber J, r espectively. Short fibers have been reported to be phagocytized by mac rophages and either cleared by ciliated mucous transport or eventually translocated to the bronchial-associated lymphoid tissue and lymph no des. The pH of the phagolysosome within the macrophage has been report ed 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 c hange significantly over time, supporting the in vitro observation of the formation of a leached layer with similar physical dimensions as t he original fiber. The clearance half-times for the three fibers evalu ated were considerably shorter than that reported for crocidolite asbe stos, a known fiber carcinogen, suggesting that these fibers would not persist in the lung as has been shown to be in the case for crocidoli te. These results demonstrate that the inhalation biopersistence model provides a sensitive means of evaluating the critical parameters of f iber biodurability and clearance in the lung. For the MMVF fibers rest ed, the longer fibers not only dissolve but also appear to break apart in the lung, thereby quickly removing the potentially carcinogenic fr action from the lung.