Tr. Gelzleichter et al., Comparison of pulmonary and pleural responses of rats and hamsters to inhaled refractory ceramic fibers, TOXICOL SCI, 49(1), 1999, pp. 93-101
The present study was designed to determine whether pleural fiber burdens o
r subchronic pleural fibroproliferative and inflammatory changes can help e
xplain the marked interspecies differences in pleural fibrosis and mesothel
ioma that are observed following long-term inhalation of RCF-1 ceramic fibe
rs by rats and hamsters. Fischer 344 rats and Syrian golden hamsters were e
xposed 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 exposur
e, For all time points, approximately 67% of fibers associated with lung ti
ssues from both rats and hamsters were longer than 5 mu m in length. In com
parison, fibers longer than 5 mu m recovered from the pleural compartment,
following a 12-week exposure and 12 weeks of recovery, accounted for 13% (h
amsters) and 4% (rats) of the distribution. In the 12 weeks after the cessa
tion of exposure, the number of fibers longer than 5 mu m in length remaine
d constant in the hamster at approximately 150 fibers per cm(2) pleura, Thi
s was 2 to 3 times the corresponding fiber surface density in the rat. Sign
ificant pulmonary and pleural inflammation was detected at all time points
and for both species. DNA synthesis by pleural mesothelial cells was quanti
fied by bromodeoxyuridine uptake following 3 days of labeling. Labeling ind
ices were higher in hamsters than in rats, both for RCF-1-exposed and filte
red air-control animals and was highest for the parietal surface of the ple
ura. Significantly greater collagen deposition was measured in the visceral
pleura of hamsters 12 weeks post-exposure but was not significantly elevat
ed in rats, These findings demonstrate that subchronic inhalation exposure
to RCF-1 induces pleural inflammation, mesothelial-cell turnover, pleural f
ibrosis, and an accumulation of fibers with a length greater than 5 mu m in
the hamster. The accumulation of long fibers in the pleural space may cont
ribute to the pathology observed in the hamster following chronic inhalatio
n of RCF-1, whereas the presence of short, thin fibers may play a role in t
he acute-phase biological response seen in both species.