You are here:
Effects of Libby amphibole exposure on the development of autoimmunity in the rat
Citation:
SALAZAR, K. D., C. B. COPELAND, AND R. W. LUEBKE. Effects of Libby amphibole exposure on the development of autoimmunity in the rat. Presented at Society of Toxicology (SOT) Annual Meeting, San Francisco, CA, March 11 - 15, 2012.
Impact/Purpose:
Our goal was to establish a relationship between increased ANA titers in Libby amphibole (LA)-exposed rats with other hallmarks of SAID.
Description:
Epidemiological data suggest that exposure to the amphibole-containing vermiculite in Libby, MT was associated with increased risk (odds ratio of 2.14) for developing systemic autoimmune diseases (SAID). Elevated titers of antinuclear antibodies (ANA) were also found in Libby residents; however, increased ANA alone are not sufficient to induce SAID. Our goal was to establish a relationship between increased ANA titers in Libby amphibole (LA)-exposed rats with other hallmarks of SAID. Female Lewis rats were intratracheally instilled biweekly for 13 weeks with total doses of 0.15, 0.5,1.5, 5.0 mg LA or 0.5 or 1.5 mg amosite (reference amphibole fiber). Blood and urine samples were collected every 4 weeks from the beginning of the study for 28 weeks and monitored for markers ofautoimmunity. ANA, antibody specificity to extractable nuclear antigens (ENA) and anti-dsDNA were measured in the serum and protein concentrations were measured in the urine. Histopathological analysis was performed on the kidneys at the conclusion of the study. ANA was significantly increased in all asbestos dose groups, however no dose response was observed. ENA analysis determined that 94% of ENA positive samples were specific for the Jo-1 antigen, a marker associated with interstitial lung disease and myositis. Urine protein concentration, anti-dsDNA titers and kidney histopathology were not affected by LA or amosite exposure. In addition, a NOAEL was not determined for ANA titers in LA-exposed rats. These data support a positive association between elevated ANA and amphibole exposure. However, enhanced ANA was not correlated with other hallmarks of SAID thus precluding a conclusion on the significance of elevated ANA. Neither anti-Jo-1 antibodies nor myositis has been reported in asbestos-exposed populations, suggesting that the Lewis rat may not be a suitable model for study. This abstract does not reflect EPA policy.