Toxicological Sciences, Vol 49, 93-101, Copyright © 1999 by Society of Toxicology
TR Gelzleichter, E Bermudez, JB Mangum, BA Wong, DB Janszen, OR Moss and JI Everitt
The present study was designed to determine whether pleural fiber burdens
or subchronic pleural fibroproliferative and inflammatory changes can help
explain the marked interspecies differences in pleural fibrosis and
mesothelioma that are observed following long-term inhalation of RCF-1
ceramic fibers by rats and hamsters. Fischer 344 rats and Syrian golden
hamsters were exposed to RCF-1 for 4 h per day, 5 days per week, for 12
consecutive weeks. Lung and pleural fiber burdens were characterized during
and after exposure. For all time points, approximately 67% of fibers
associated with lung tissues from both rats and hamsters were longer than 5
microns in length. In comparison, fibers longer than 5 microns recovered
from the pleural compartment, following a 12-week exposure and 12 weeks of
recovery, accounted for 13% (hamsters) and 4% (rats) of the distribution.
In the 12 weeks after the cessation of exposure, the number of fibers
longer than 5 microns in length remained constant in the hamster at
approximately 150 fibers per cm2 pleura. This was 2 to 3 times the
corresponding fiber surface density in the rat. Significant pulmonary and
pleural inflammation was detected at all time points and for both species.
DNA synthesis by pleural mesothelial cells was quantified by
bromodeoxyuridine uptake following 3 days of labeling. Labeling indices
were higher in hamsters than in rats, both for RCF-1-exposed and filtered
air-control animals and was highest for the parietal surface of the pleura.
Significantly greater collagen deposition was measured in the visceral
pleura of hamsters 12 weeks post-exposure but was not significantly
elevated in rats. These findings demonstrate that subchronic inhalation
exposure to RCF-1 induces pleural inflammation, mesothelial-cell turnover,
pleural fibrosis, and an accumulation of fibers with a length greater than
5 microns in the hamster. The accumulation of long fibers in the pleural
space may contribute to the pathology observed in the hamster following
chronic inhalation of RCF- 1, whereas the presence of short, thin fibers
may play a role in the acute-phase biological response seen in both
species.
ARTICLES
Comparison of pulmonary and pleural responses of rats and hamsters to inhaled refractory ceramic fibers
Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709, USA.
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