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Subchronic Inhalation Exposure of Rats to Libby Amphibole and Amosite Asbestos: Effects at 18 Months Post Exposure
Citation:
Dodd, D., G. Willson, K. Roberts, H. Wall, A. Jarabek, AND S. Gavett. Subchronic Inhalation Exposure of Rats to Libby Amphibole and Amosite Asbestos: Effects at 18 Months Post Exposure. Presented at Society of Toxicology, Phoenix, AZ, March 23 - 27, 2014.
Impact/Purpose:
This study examined the relative pathogenic activity of Libby amphibole fibers relative to a well-characterized amosite control asbestos fiber sample in a subchronic rat inhalation study followed out to 18 months post-exposure. The study supports the risk assessment of the Libby, MT superfund site.
Description:
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 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, 3.32, 10.06 mg/m3; 159, 693, 1522 fibers/cc), or amosite (AM; 3.34 mg/m3; 230 f/cc). Toxicity endpoints, pathology, and fiber burden evaluation were determined 18 mo post-exposure. Fiber exposure had no effect on survival. Mononuclear cell leukemia was the main cause of death prior to scheduled necropsy in all groups except the LA 3.3 group, though group incidences were below NTP historical control data. BAL cell numbers, LDH, and protein in AM and LA groups were not statistically different from the control group (n=8 rats/group), indicating resolution of earlier inflammation (Dodd, SOT 2012; Willson, SOT 2013). Histopathology of the left lung lobe, trachea, sternum, pleura, epididymis and testes, and relevant gross tissue lesions was conducted on 50 rats/group. Alveolus inflammation, pleural fibrosis, lung interstitial fibrosis, and the presence of foreign bodies were noted in all fiber-exposed groups. A greater incidence of chronic tracheal inflammation was noted in the LA groups. Alveolar bronchiolar adenoma occurred in 2 rats in each of the AM, MED LA, and HI LA groups, and 1 alveolar bronchiolar carcinoma was observed in the HI LA group; all of these findings were within historical NTP control data. No pleural mesotheliomas were observed in any treatment groups. In conclusion, both AM and LA induced dose-related lung fibrotic responses; tumor incidences were apparently increased but not beyond historical control ranges. Tissue fiber burden data are supporting dosimetry model development; comparisons of responses between fibers may change based on internal dose estimates. (This abstract does not represent US EPA policy.)