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Exposure to Sumas Mountain chrysotile induces similar gene expression changes as Libby Amphibole but has greater effect on long-term pathology and lung function
Citation:
Cyphert, J., A. Nyska, R. Mahoney, M. Schladweiler, U. Kodavanti, AND S. Gavett. Exposure to Sumas Mountain chrysotile induces similar gene expression changes as Libby Amphibole but has greater effect on long-term pathology and lung function. Presented at Society of Toxicology annual meeting, March 10 - 14, 2013.
Impact/Purpose:
Comparison of pathologies in rats after exposure to 4 types of asbestos shows that Libby, MT amphibole (LA) and Sumas Mountain (SM), WA chrysotile elicit comparable gene expression profile changes suggestive of dysregulation of extracellular matrix and fibrosis pathways. Despite the equivalent changes, SM was more potent in inducing fibrotic changes in the lung than LA. The data suggest a cause for concern of exposure to SM chrysotile, and highlights the need for further study of sites where naturally occuring asbestos is present
Description:
This study was designed to provide understanding of the toxicity of naturally occurring asbestos (NOA) including Libby amphibole (LA), Sumas Mountain chrysotile (SM), El Dorado Hills tremolite (ED) and Ontario ferroactinolite cleavage fragments (ON). Rat-respirable fractions (aerodynamic diameter ≤ 2.5 μm) were prepared by water elutriation and a dose of 1.5 mg/rat delivered via a single intratracheal (IT) instillation. Bronchoalveolar lavage (BAL), gene expression, histopathology, and lung function were analyzed 1 d, 3 mo, or 15 mo post-instillation. One day after exposure, although inducing less acute inflammation than other samples, LA and SM induced a greater degree of lung injury. A similar trend was also observed in gene expression profiles, as both LA- and SM-exposed rats differed significantly from dispersion media (DM) controls. Changes were suggestive of dysregulation of both extracellular matrix and fibrosis pathways. By three months, most BAL parameters had returned to DM control levels. However, significant time-dependent fibrosis was evident in rats exposed to LA or SM. By 15 months, the greatest fibrotic changes were observed in SM-exposed rats; while no fibrosis was noted in the cleavage-fragment or DM control group (SM>LA>ED>ON=DM). Consistent with the greatest degree of fibrosis, only SM-exposed rats exhibited persistent, long-term changes in lung function parameters. These data demonstrate that, in the rat, SM resulted in more significant long-term effects after a single IT exposure than LA. This study suggests that there may be cause for concern for people at risk of being exposed to NOA from the Sumas Mountain landslide, and highlights the need for further study of sites where NOA is present. (This abstract does not represent U.S. EPA policy).