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Subchronic inhalation exposure of rats to Libby amphibole and amosite asbestos: Effects at 1 and 3 months post exposure#
Citation:
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 Toxicologic Pathology, Portland, OR, June 16 - 20, 2013.
Impact/Purpose:
Subchronic inhalation exposures of male rats to airborne Libby, Montana amphibole fibers (LA) or amosite fibers (AM) were conducted, and the results show comparable fibrogenic responses 1 and 3 months after exposure to either LA and AM asbestos. The results will support dosimetry model development and advance understanding of the comparative toxicity of different forms of site-specific asbestos.
Description:
Increased asbestosis, lung cancer, and mesothelioma rates are evident in humans after exposures to Libby amphibole (LA). To support dosimetry model development and compare potency, a subchronic nose-only inhalation 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. Previous results showed comparable inflammatory and fibrogenic responses 1 d after exposure to MED LA and AM. Here we report BAL neutrophils increased in HI LA and AM groups at 1 mo, but only in 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. Cytokine production and activation of pro-fibrotic and cellular growth signaling pathways were comparable between AM and MED LA. Lung histopathology demonstrated minimal increases in alveolus inflammation, interstitial fibrosis, bronchiolization, and foreign body in AM and LA groups compared to controls. Alveolus inflammation was most severe in HI LA rats at 1 and 3 mo compared to 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. Dosimetry modeling using fiber burdens may provide additional insights for comparison.