title: Comparison of pulmonary and pleural responses of rats and hamsters to inhaled refractory ceramic fibers.
abstract: 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.
authors.affiliation: Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709, USA.
authors.forename: T R
authors.initials: TR
authors.lastname: Gelzleichter
authors.forename: E
authors.initials: E
authors.lastname: Bermudez
authors.forename: J B
authors.initials: JB
authors.lastname: Mangum
authors.forename: B A
authors.initials: BA
authors.lastname: Wong
authors.forename: D B
authors.initials: DB
authors.lastname: Janszen
authors.forename: O R
authors.initials: OR
authors.lastname: Moss
authors.forename: J I
authors.initials: JI
authors.lastname: Everitt
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002516:Ceramics / Q000633:toxicity*; D003094:Collagen / Q000032:analysis; D006224:Cricetinae; D004247:DNA / Q000096:biosynthesis*; D005355:Fibrosis / Q000139:chemically induced; D007249:Inflammation / Q000139:chemically induced; D008168:Lung / Q000187:drug effects; D008297:Male; D008654:Mesothelioma / Q000139:chemically induced*; D019016:Mineral Fibers / Q000633:toxicity*; D010994:Pleura / Q000187:drug effects / Q000473:pathology*; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D012137:Respiratory System / Q000187:drug effects*; D013045:Species Specificity; D013997:Time Factors
chemical_list: D019016:Mineral Fibers; D003094:Collagen; D004247:DNA