Comparison of inhaled dose vs. postexposure time period in silica-induced pulmonary toxicity in the rats
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2015/03/01
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Personal Author:Chen BT ; Frazer DG ; Gu J ; Joseph P ; Kashon ML ; McKinney W ; Richardson D ; Roberts, Jennifer R. ; Sellamuthu R ; Umbright C ; Young S
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Description:Occupational exposure to respirable crystalline silica results in silicosis, cancer, autoimmune diseases, tuberculosis, and renal diseases. Currently, we have investigated and compared the effect of dose vs. post-exposure time period in the pulmonary toxicity induced by inhalation exposure of rats to crystalline silica. Rats were exposed by inhalation to respirable crystalline silica (Min-U-Sil 5 Silica, U.S. Silica, Berkeley Springs, West Virginia) at a concentration of 15 mg/m3, 6 hours per day, 5 days/ week for one week or 12 consecutive weeks. The rats exposed to silica for 1 week were maintained under standard animal housing conditions for 44 weeks following termination of their exposure to silica and euthanized. The rats exposed to silica for 12 weeks were euthanized soon after termination of the silica exposure. The total amount of silica inhaled by the 12-week exposure group of rats was roughly 12-times more than that of the 44-week post-exposure group. Silica-induced pulmonary toxicity was determined in both groups of rats on the basis of bronchoalveolar lavage fluid (BALF) parameters of toxicity [lactate dehydrogenase (LDH) activity, albumin content, total number of alveolar macrophages (AMs) and polymorphonuclear leukocytes (PMNs), and inflammatory cytokine levels], lung histology, and global gene expression changes in the lungs. Induction of significant pulmonary toxicity was identified in both groups of rats based on the various pulmonary toxicity parameters analyzed. However, the magnitude of changes in the majority of the pulmonary toxicity parameters determined was significantly higher in the rats belonging to the 44-week post silica exposure time period group compared to the 12-week silica exposure group. These results collectively suggested that the post silica exposure time period is more critical to silica-induced pulmonary toxicity than the inhaled dose of crystalline silica in the rats. [Description provided by NIOSH]
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ISSN:1096-6080
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Volume:144
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Issue:1
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NIOSHTIC Number:nn:20045982
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Citation:Toxicologist 2015 Mar; 144(1):337
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Federal Fiscal Year:2015
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Peer Reviewed:False
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Source Full Name:The Toxicologist. Society of Toxicology 54th Annual Meeting and ToxExpo, March 22-26, 2015, San Diego, California
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Main Document Checksum:urn:sha-512:4a272e058cbfe76d25c5e612cfb86fd5f3ddca84fe7dcb8e1fc6267b55e6d19c8ed1145ae25c9708bb47b5bf4869fd2f5d869f37a4da93937363749d204bf7af
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