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HERO ID
48642
Reference Type
Journal Article
Title
Regression of pulmonary lesions produced by inhaled titanium dioxide in rats
Author(s)
Baggs, RB; Ferin, J; Oberdorster, G
Year
1997
Is Peer Reviewed?
1
Journal
Veterinary Pathology
ISSN:
0300-9858
Volume
34
Issue
6
Page Numbers
592-597
Language
English
PMID
9396140
Web of Science Id
WOS:A1997YG72600007
Abstract
Inhaled ultrafine particles of TiO2 (TiO2-D, 20 nm particle size) lead to a greater pulmonary inflammatory response than larger pigment-grade particles (TiO2-F, 250 nm). Male Fisher 344 rats were exposed for 6 hours a day, 5 days a week, for 3 months to 1) filtered air (control); 2) TiO2-F, 22.3 mg/m3; 3) TiO2-D, 23.5 mg/m3; or 4) crystalline SiO2, a positive control particle (approximately 800 nm particle size, 1.3 mg/m3). Groups of 3-4 animals were sacrificed at 6 and 12 months following the completion of exposure. Pulmonary effects of exposure were evaluated using standard hematoxylin and eosin-stain sections, histochemical stains for collagen, and immunohistochemical assays for cell turnover. Six months after animals were exposed to SiO2, they had moderate focal interstitial fibrosis and moderately severe focal alveolitis. Animals exposed to TiO2-D had slightly less fibrosis. The least fibrosis was seen in the TiO2-F group. At 1 year after exposure, fibrosis was still present but decreased in the SiO2 group. The amount of interstitial fibrosis in the TiO2-D- and TiO2-F-treated animals had largely returned to untreated control levels, although an increased number of alveolar macrophages persisted, usually with retained particles. There was discordance between bromodeoxyuridine and proliferating cell nuclear antigen indices, most probably due to cytokine elaboration in the areas of inflammation, which may have altered the expression of proliferating cell nuclear antigens. There was no detectable fibroblast labeling at the 6-month observation and only very low levels at 12 months. Thus, although initially irritant, TiO2-induced lesions regressed during a 1-year period following cessation of exposure.
Keywords
cell proliferation; fibrosis; rat; silica; titanium dioxide
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