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Comparative Long-Term Toxicity of Libby Amphibole and Amosite Asbestos after Single or Multiple Intratracheal Exposures
Citation:
Cyphert, J., D. Padilla-Carlin, A. Nyska, M. Schladweiler, A. Ledbetter, J. Shannahan, U. Kodavanti, AND S. Gavett. Comparative Long-Term Toxicity of Libby Amphibole and Amosite Asbestos after Single or Multiple Intratracheal Exposures. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. Taylor & Francis, Inc., Philadelphia, PA, 78(3):151-65, (2015).
Impact/Purpose:
Results from comparative pulmonary toxicology studies of Libby amphibole and amosite asbestos in rats are reported as part of the Libby Action Plan. The samples were given by intratracheal instillation in single or multiple doses, and responses compared up to 20 months post-exposure. Equivalent doses given over multiple exposures, representing more closely repeated low-dose inhalation exposure in humans, were shown to cause slightly greater pathogenesis, and both samples induced a small number of cancers and mesotheliomas in rats. These studies will help to inform the risk assessment of Libby amphibole in exposed populations.
Description:
In former mine workers of Libby, Montana, exposure to amphibole-containing vermiculite has been linked to increased rates of asbestosis, lung cancer, and mesothelioma. Although many studies have shown adverse effects of Libby Amphibole (LA) exposure, little is known regarding the relative toxicity compared to regulated asbestos, or the risks associated with acute high dose exposures relative to repeated low dose exposures. In this study, pulmonary function, inflammation and pathology were assessed after single or multiple intratracheal (IT) exposures of LA or a well-characterized amosite (AM) control fiber with equivalent fiber characteristics. Male F344 rats were exposed to an equivalent total mass dose (0.15, 0.5, 1.5, or 5.0 mg/rat) of LA or AM administered either as a single IT instillation, or as multiple ITs given every other week over a 13 week period, and necropsied up to 20 months after the initial IT. In both studies, LA resulted in slightly greater acute neutrophilic inflammation and cellular toxicity than equal doses of AM, but the long-term histopathological changes were approximately equivalent between fibers, suggesting that LA is at least as toxic as AM. Conversely, an equal mass dose given over multiple exposures instead of a single bolus resulted in greater chronic pathological changes in the lung despite the initially weaker acute inflammatory response. Although no dose-response relationship could be discerned, mesothelioma and lung carcinoma were found after exposure to low and high dose levels of LA or AM. Overall, these results suggest that there is a possibility of greater long-term pathological changes with repeated lower LA dose exposures, which more accurately models chronic environmental exposures.
