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Subchronic Inhalation Exposure of Rats to Libby Amphibole and Amosite Asbestos: Effects at 1 and 3 Months Post Exposure**
Willson, G., D. Dodd, K. Roberts, H. Wall, J. Cyphert, A. Jarabek, AND S. Gavett. Subchronic Inhalation Exposure of Rats to Libby Amphibole and Amosite Asbestos: Effects at 1 and 3 Months Post Exposure**. Presented at Society of Toxicology, March 10 - 14, 2013.
Increased asbestosis, lung cancer, and mesothelioma rates are evident after exposures to Libby amphibole (LA). To support dosimetry model development and compare potency, a subchronic nose-only inhalation exposure study (6 hr/d, 5 d/wk, 13 wk) was conducted in male F344 rats. Rats were exposed to air (control), LA (LO, MED, HI; 1.01, 3.33, 10.08 mg/m3; 300, 701, 4050 fibers/cc), or amosite (AM; 3.35 mg/m3; 1035 f/cc). Toxicity endpoints, pathology, and fiber burden evaluation were determined 1 d and 1, 3, and 18 mo post-exposure. Previously reported results (Dodd, SOT 2012) showed comparable inflammatory and fibrogenic responses 1 d after subchronic exposure to MED LA and AM. Here we report BAL neutrophils were increased in HI LA and AM groups at 1 mo, but only in HI and MED LA groups at 3 mo. Macrophages were decreased in the HI and MED LA groups at 3 mo. AM and MED LA groups had comparable increases in BAL LDH and protein at 1 and 3 mo. Lung tissue cytokine production and activation of pro-fibrotic and cellular growth signaling pathways were also comparable between AM and MED LA. Histopathological examination of the lung found a minimal increase in alveolus inflammation, interstitial fibrosis, bronchiolization, and foreign body presence in both AM and LA groups compared to controls. Alveolus inflammation was most severe in HI LA rats at 1 and 3 mo compared to all other exposure groups. Only HI LA rats had bronchiole epithelial hyperplasia, but only 1 mo after exposure. These results show comparable fibrogenic responses 1 and 3 mo after subchronic exposure of rats to LA and AM asbestos. Fiber burdens are being measured to support dosimetry model development of deposition and clearance (Asgharian, SOT 2012: Jarabek, SOT 2013); comparison based on tissue dose may change the relationship. (This abstract does not represent US EPA policy)
These results show comparable fibrogenic responses 1 and 3 mo after subchronic exposure of rats to Libby amphibole (LA) and amosite asbestos, suggesting LA is not uniquely potent compared to other forms of asbestos.
URLs/Downloads:WILLSON SUBCHRONIC LA INHALATION SOT ABSTRACT 2013 FINAL.DOCX
Record Details:Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB
ENVIRONMENTAL PUBLIC HEALTH DIVISION
CARDIOPULMONARY AND IMMUNOTOXICOLOGY BRANCH