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Acute Toxicological Responses of Fischer Rats to Naturally Occurring Asbestos from theUnited States and Canada
Citation:
Cyphert, J. M., D. J. Padilla-Carlin, A. Nyska, J. Shannahan, M. SCHLADWEILER, U. P. KODAVANTI, AND S. H. GAVETT. Acute Toxicological Responses of Fischer Rats to Naturally Occurring Asbestos from theUnited States and Canada. Presented at Society of Toxicology (SOT) Annual Meeting, San Francisco, CA, March 11 - 15, 2012.
Impact/Purpose:
One day and 3 months after intratracheal instillation in the rat, Sumas Mountain chrysotile caused more significant fibrosis and impairment of baseline lung function than exposure to Libby amphibole, Ontario actinolite, and EI Dorado tremolite (SM>LA>ON>ED).
Description:
This study was designed to provide understanding of the toxicity of naturally occurring asbestos (NOA) including Libby amphibole (LA), Sumas Mountain chrysotile (SM), EI Dorado Hills tremolite (ED) and Ontario actinolite/ferroactinolite cleavage fragments (ON). Ratrespirable fractions (aerodynamic diameter ≤2.5 um) were prepared by water elutriation and delivered via a single intratracheal (IT) instillation at doses of 0.5 and 1.5 mg/rat. Bronchoalveolar lavage fluid (BALF), lung histology, and baseline pulmonary function were analyzed 1 d and 3 mo post-IT. One day post-IT, low-dose NOA exposure resulted in a 3-4 fold increase in BALF cellularity compared to dispersion media (DM) controls, whereas high-dose exposure had a more severe effect on lung inflammation which varied by source. Although inducing less acute inflammation than ON and ED, exposure to either LA or SM resulted in increased eosinophilia, as well as a greater degree of acute lung injury. Additionally, an increase in Penh (correlated with airway resistance), was only noted in rats exposed to high-dose LA or SM. Three months post-IT, most BALF parameters had returned to DM control levels. Despite a relative return to baseline oflung inflammatory and injury markers, the development of fibrosis, as determined histologically, was greatest in SM-exposed rats (SM>LA>ON>ED). Consistent with this, elevated Penh was only noted in high-dose SM-exposed rats. These data demonstrate that, in the rat, SM results in more significant fibrosis and impairment of baseline lung function than exposure to 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).