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AcuteToxicological Responses of Fischer Rats to Naturally Occurring Asbestos Samples from the United States and Canada
Citation:
Cyphert, J. M., D. J. Padilla-Carlin, M. SCHLADWEILER, A. Nyska, J. H. Shannahan, U. P. KODAVANTI, AND S. H. GAVETT. AcuteToxicological Responses of Fischer Rats to Naturally Occurring Asbestos Samples from the United States and Canada. Presented at 2011 North Carolina Society of Toxicology President's Award for Research Competition (PARC), RTP, NC, September 22, 2011.
Impact/Purpose:
Exposure to 4 forms of asbestos induces variable inflammatory, fibrogenic, and pulmonary function responses in Fischer rats, with Sumas Mountain chrysotile and Libby amphibole inducing the greatest responses
Description:
The potential public health issues related to exposure to natural asbestos deposits (commonly termed naturally occurring asbestos, NO A) has gained the regulatory and media spotlight in recent years. Arguably the most well known example is Libby, Montana, the site of the largest vermiculite ore mine in the United States. The ore mined from this site contains a significant amount of amphibole asbestos, termed "Libby Amphibole" (LA). Occupational and environmental exposure to LA has been associated with a nurnber of asbestos-related diseases including asbestosis, pleural disease, lung cancer, and mesothelioma in workers and residents of the immediate town and surrounding communities (McDonald, Harris, and Armstrong 2004; Sullivan 2007; (ATSDR) 2002). Whereas a small, but significant body of research has demonstrated the relative toxicity of LA, both epidemiologically and in animal models, little is known about other sites of NOA within the United States such as Whatcom County, Washington, the site of the Sumas Mountain landslide, and El Dorado Hills, California. To support risk assessment efforts, a comparative study was designed to provide understanding of the toxicity ofdifferent types of fibers encountered in EPA clean-up efforts. Physico-chemical properties, and consequentially toxicity, are likely to be different among various fiber types. NOA samples representing different types of asbestiform fibers or nonasbestiform cleavage fragments included LA (composed of winchite/richterite/tremolite and served as a positive control), chrysotile from Whatcom County/Sumas Mountain, Washington (SM), tremolite from El Dorado Hills, California (ED) and actinolite/ferroactinolite cleavage fragments from Ontario, Canada (ON) which served as a "negative" control. Rat-respirable fractions (aerodynamic equivalent diameter ≤2.5 um) of each NOA were prepared by water elutriation, resuspended in dispersion media (containing albumin and surfactant), and delivered via a single intratracheal (IT) instillation to 9-10 wk old male Fischer rats at doses of 0.5 mg/rat and 1.5 mg/rat. Bronchoalveolar lavage fluid (BALF), lung histology, and baseline pulmonary function were analyzed 1 day and 3 months post-IT to determine the acute toxicity of each NOA sample compared to a vehicle (dispersion media, DM) control. At 1 day post-instillation, BALF cellularity was significantly increased in all asbestos exposed groups. Low-dose (0.5 mg/rat) exposure to all samples resulted in a 3-4 fold increase in total cells compared to controls, whereas high-dose (l.5 mg/rat) exposure had a more severe effect on lung inflammation which varied by source of the fiber. Exposure to high-dose LA resulted in a 4 fold increase in total cells, SM a 7 fold increase and both ON and ED exposure resulted in a 9 fold increase compared to DM controls. Although inducing less acute inflammation, exposure to either LA or SM resulted in increased neutrophils and eosinophils, as well as a greater degree of acute lung injury. This trend in lung injury was reflected in baseline lung function. One day after instillation, an increase in Penh, a parameter 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. However, total cells were still increased 1.5 fold over DM controls in high-dose LA, ON, and ED-exposed rats. Additionally, several lung injury markers remained elevated in LA-exposed, and to a lesser extent in high-dose ED and SM-exposed, rats. Despite a relative return to baseline of lung inflammatory and injury markers, the greatest dose-dependent development of fibrosis was seen in SM-exposed rats (SM>LA>ON>ED). Consistent with the greatest degree of fibrosis, only high-dose SM-exposed rats exhibited elevated resting Penh 3 months after exposure. These data demonstrate that, in the rat, similar mass dose exposures to SM resulted in more significant acute toxicological effects (development of fibrosis and impairment of baseline lung function) than exposure to LA. Given the severe health effects of LA exposure in residents of Libby (Sullivan 2007; Vinikoor et al. 2010), this study would suggest that there may be cause for concern for the residents in Whatcom County that are at risk of being exposed to NOA from the Sumas Mountain landslide, and highlights the need for further research and study of sites where NOA is present. (This abstract does not represent U.S. EPA policy).