You are here:
SUBCHRONIC INHALATION EXPOSURE OF RATS TO LIBBY AMPHIBOLE AND AMOSITE ASBESTOS
Citation:
Dodd, D. E., E. W. Tewksbury, K. Roberts, A. M. JARABEK, G. A. Wilson, H. G. Wall, AND S. H. GAVETT. SUBCHRONIC INHALATION EXPOSURE OF RATS TO LIBBY AMPHIBOLE AND AMOSITE ASBESTOS. Presented at Society of Toxicology (SOT) Annual Meeting, San Francisco, CA, March 11 - 15, 2012.
Impact/Purpose:
The goal of this research is to support biological potency assessment and dosimetry model development. The study shows comparable inflammatory and fibrogemc responses 1 day after subchromc exposure of rats to LIbby amphibole and amosite asbestos
Description:
Exposure to Libby amphibole (LA) is associated with significant increases in asbestosis, lung cancer, and mesothelioma. To support biological potency assessment and dosimetry model development, 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 gravimetric concentration; 43, 171, 280 particles/cc by APS, respectively), or amosite (AM; 3.35 mg/m3; 404 particles/cc). No clinical findings were observed during the exposures though average body weights were 4% lower than controls in the AM group for weeks 2-14. One day after final exposure, significant increases in BAL LDH (2-2.5x) and total protein (1.5-1.7x) were found in MED and HI LA groups, but no significant changes were found in the AM group at the same mass exposure as MED LA. BAL ALP and NAG concentrations were similar in all exposure groups including the control. Changes observed in BAL cells were significant decreases in percentages of macrophages (59% vs. 90%) and increases in percentages of lymphocytes (l.4x) and neutrophils (4x) in HI LA vs. control. Histopathological examination of the lung found a minimal increase in alveolus inflammation, interstitial fibrosis, bronchiolization, and foreign body presence in all rats (8/8) in LO LA, MED LA, and AM groups compared to controls. Alveolus inflammation was more severe in all (8/8) HI LA rats. The HI LA group was the only exposure group showing bronchiole epithelial hyperplasia (8/8 were minimal grade). Other groups of rats were necropsied 1 and 3 months post-exposure (also 8/group), with the final necropsy planned for 18 months post-exposure (50/group). Tissue fiber burdens are being determined to support dosimetry model development. Results show comparable inflammatory and fibrogenic responses 1 day after subchronic exposure ofrats to LA and AM asbestos. (The views expressed in this abstract are those ofthe authors and do not necessarily reflect the views or policies of the U.S. Environmental Protection Agency