Comparison of pulmonary and pleural responses of rats and hamsters to inhaled refractory ceramic fibers

The present study was designed to determine whether pleural fiber burdensor subchronic pleural fibroproliferative and inflammatory changes can helpexplain the marked interspecies differences in pleural fibrosis andmesothelioma that are observed following long-term inhalation of RCF-1ceramic fibers by rats and hamsters. Fischer 344 rats and Syrian goldenhamsters were exposed to RCF-1 for 4 h per day, 5 days per week, for 12consecutive weeks. Lung and pleural fiber burdens were characterized duringand after exposure. For all time points, approximately 67% of fibersassociated with lung tissues from both rats and hamsters were longer than 5microns in length. In comparison, fibers longer than 5 microns recoveredfrom the pleural compartment, following a 12-week exposure and 12 weeks ofrecovery, accounted for 13% (hamsters) and 4% (rats) of the distribution.In the 12 weeks after the cessation of exposure, the number of fiberslonger than 5 microns in length remained constant in the hamster atapproximately 150 fibers per cm2 pleura. This was 2 to 3 times thecorresponding fiber surface density in the rat. Significant pulmonary andpleural inflammation was detected at all time points and for both species.DNA synthesis by pleural mesothelial cells was quantified bybromodeoxyuridine uptake following 3 days of labeling. Labeling indiceswere higher in hamsters than in rats, both for RCF-1-exposed and filteredair-control animals and was highest for the parietal surface of the pleura.Significantly greater collagen deposition was measured in the visceralpleura of hamsters 12 weeks post-exposure but was not significantlyelevated in rats. These findings demonstrate that subchronic inhalationexposure to RCF-1 induces pleural inflammation, mesothelial-cell turnover,pleural fibrosis, and an accumulation of fibers with a length greater than5 microns in the hamster. The accumulation of long fibers in the pleuralspace may contribute to the pathology observed in the hamster followingchronic inhalation of RCF- 1, whereas the presence of short, thin fibersmay play a role in the acute-phase biological response seen in bothspecies.