Comparison of pleural responses of rats and hamsters to subchronic inhalation of refractory ceramic fibers.

Abstract

In the present subchronic study, we compared pleural inflammation, visceral pleural collagen deposition, and visceral and parietal pleural mesothelial cell proliferation in rats and hamsters identically exposed to a kaolin-based refractory ceramic fiber, (RCF)-1 by nose-only inhalation exposure, and correlated the results to translocation of fibers to the pleural cavity. Fischer 344 rats and Syrian golden hamsters were exposed to 650 fibers/cc of RCF-1, for 4 hr/day, 5 days/week for 12 weeks. Following 4 and 12 weeks of exposure, and after a 12-week recovery period, pleural lavage fluid was analyzed for cytologic and biochemical evidence of inflammation. Visceral and parietal pleural mesothelial cell proliferation was assessed by immunocytochemical detection of bromodeoxyuridine incorporation. Pleural collagen was quantitated using morphometric analysis of lung sections stained with Sirius Red. Fiber-exposed rats and hamsters had qualitatively similar pleural inflammation at each time point. Mesothelial cell proliferation was more pronounced in hamsters than in rats at each time point and at each site. In both species, the mesothelial cell labeling index was highest in the parietal pleural mesothelial cells lining the surface of the diaphragm at each time point. Hamsters but not rats had significantly elevated collagen in the visceral pleura at the 12-week postexposure time point. Fibers were found in the pleural cavities of both species at each time point. These fibers were generally short and thin. These results suggest that mesothelial cell proliferation and fibroproliferative changes in the pleura of rodents following short-term inhalation exposure are associated with fiber translocation to the pleura and may be predictive of chronic pleural disease outcomes following long-term exposure.

Proliferative and Nonproliferative Lesions of the Rat and Mouse Respiratory Tract

“…Hyperplastic mesothelial response to instilled particulates is reported to be most severe in parietal pleura lining diaphragmatic surface (Everitt et al 1997). …”

“…Mesothelioma: Evidence of cellular atypia and/or invasion of adjacent lung parenchyma or thoracic wall Pleural fibrosis and associated inflammation: Presence of interlacing bundles of spindle cells with some evidence of collagen formation and associated inflammatory cells; no evidence of proliferating mesothelium Comment: Considerable information is available on the morphology and biologic potential of hyperplastic and inflammatory pleural responses to instilled particulates in rodents (Everitt et al 1994(Everitt et al , 1997.…”

Malignant Mesothelioma: Mechanism of Carcinogenesis

“…These growth factors were able to induce proliferation of mesothelial cells in culture. This inflammatory response may be triggered by fiber translocation to the pleura as demonstrated in rodents exposed to glass fibers or to RCF [25,26]. Several studies have demonstrated the presence of asbestos fibers in the human pleura [9,10,27].…”

“…Biopersistence of natural and man-made fibers in the lungs [99] or peritoneal cavity [100] is an important characteristic of fibrous materials that induce lung cancer and diffuse malignant mesothelioma in rodents following inhalation [19]. Man-made mineral fibers developed as asbestos fiber substitutes, especially refractory ceramic fibers [26] and silicon carbide whiskers, have been shown to be biopersistent [101] following inhalation by rodents. Following inhalation by hamsters, refractory ceramic fibers translocated to the pleura and induced mesothelial cell proliferation and fibrosis [26].…”

Special-Purpose Fiber Type 475—Toxicological Assessment

“…5. The hamster pleura have been found to be excessively sensitive and to have substantially more pleural inflammatory-cell response and mesothelial inflammation (Everitt et al, 1997;Gelzleichter et al, 1999).…”