You are here:
LONG TERM RESPONSE OF RATS TO SINGLE INTRATRACHEAL EXPOSURE OF LIBBY AMPHIBOLE (LA) OR AMOSITE
Citation:
Cyphert, J. M., D. J. Padilla-Carlin, M. SCHLADWEILER, Nyska, A. Nyska, J. H. Shannahan, U. P. KODAVANTI, AND S. H. GAVETT. LONG TERM RESPONSE OF RATS TO SINGLE INTRATRACHEAL EXPOSURE OF LIBBY AMPHIBOLE (LA) OR AMOSITE. Presented at Society of Toxicology (SOT) Annual Meeting, Washington, DC, March 06 - 10, 2011.
Impact/Purpose:
The study shows that amosite and Libby amphibole caused significant differences in collagen deposition, fibrosis development at the same mass dose, 1 and 2 years after intratracheal instillation.
Description:
In former mine workers of Libby, Montana, exposure to amphibole-contaminated vermiculite has been associated with increased incidences of asbestosis and mesothelioma. In this study, we investigated long term effects of Libby amphibole (LA) exposure 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 single doses of either saline, amosite (0.65 mg/rat), or LA (0.65 or 6.5 mg/rat) by intratracheal instillation. One year after exposure, blood and bronchoalveolar lavage fluid parameters were at control levels, consistent with inflammation in the lungs being specifically intra-alveolar and interstitial. Inflammation was characterized as predominantly macrophage accumulation near terminal and respiratory bronchioles. Two years post-exposure, no potential preneoplastic changes were seen pathologically or in lung biomarker evaluation of any groups. LA caused dose-related increases in multifocal intraalveolar and interstitial accumulation of macrophages and fibroblasts, but little collagen depositon was seen. Amosite caused interstitial nodules composed of fibroblasts and multinucleated giant cells, with significant increases in collagen deposition. Surprisingly, expression of fibrosis markers Col 1A1 and Col 3A1, while trending to increase in all asbestos exposed groups, did not reach statistical significance in amosite exposed rats, suggesting that the fibrosis is no longer active. Conversely, both Col 1A1 and Col 3A1 were significantly elevated in LA-exposed rats indicating that, although no collagen deposition was present histologically at 0.65 rng/rat LA, fibrosis may be initiating at this later stage. These results show that there are significant differences in long term toxicity of LA and amosite administered at the same mass dose. (This abstract does not represent U.S. EPA policy).