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Long term response of rats to single intratracheal exposure of Libby amphibole or amosite
Cyphert, J. M., D. J. Padilla-Carlin, M. SCHLADWEILER, M. C. Shannahan, A. Nyska, U. P. KODAVANTI, AND S. H. GAVETT. Long term response of rats to single intratracheal exposure of Libby amphibole or amosite. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH - PART A: CURRENT ISSUES. Taylor & Francis, Inc., Philadelphia, PA, 75(3):183-200, (2012).
In former mine workers and residents of Libby, Montana, exposure to amphibolecontaminated vermiculite has been associated with increased incidences of asbestosis and mesothelioma. In this study, we investigated long-term effects of Libby amphibole (LA) exposure relative to the well-characterized amosite asbestos in a rat model. Rat respirable fractions of LA and amosite (aerodynamic diameter ≤2.5 um) were prepared by water elutriation. Male F344 rats were exposed to a single dose of either saline, amosite (0.65 mg/rat), or LA (0.65 or 6.5 mg/rat) by intratracheal (IT) instillation. One year after exposure, asbestos exposed rats had chronic pulmonary inflammation and fibrosis. Two years post-exposure, lung inflammation and fibrosis had progressed in a time and dose-dependent manner in LA-exposed rats, although the severity of inflammation and fibrosis was smaller in magnitude than in animals exposed to amosite. In contrast, gene expression of the fibrosis markers Col 1A2 and Col 3A1 was significantly greater in LA-exposed animals compared to amosite-exposed rats. There was no evidence of preneoplastic changes in any of the asbestos-exposed groups. However, all asbestos-exposed rats had a significant increase in the expression ofepidermal growth factor receptor (EGFR) two years after instillation. In addition, only LA-exposed rats had significant increases in mesothelin (Msln) and Wilms' tumor gene (WT1) expression suggesting possible induction of tumor pathways. These results show that a single IT exposure to LA is sufficient to induce significant fibrogenic, but not carcinogenic, effects up to 2 years after exposure that differ both in quality and magnitude from those elicited by amosite administration at the same mass dose in F344 rats: LA was on a mass basis less potent than amosite.
Exposure to Libby Amphibole (LA) caused increases in collagen, EGFR, mesothelin, and WT1 expression in lungs of Fischer rats 2 years after exposure. However average fibrosis scores were higher in amosite-exposed rats vs. LA-exposed rats.
URLs/Downloads:JOURNAL OF TOXICOLOIGICAL AND ENVIRONMENTAL HEALTH A Exit
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB
ENVIRONMENTAL PUBLIC HEALTH DIVISION
CARDIOPULMONARY AND IMMUNOTOXICOLOGY BRANCH