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TWO-WEEK INHALATION EXPOSURE OF RATS TO LIBBY AMPHIBOLE (LA) AND AMOSITE ASBESTOS
Citation:
GAVETT, S. H., A. M. JARABEK, E. W. Tewksbury, E. Bermudez, V. A. Wong, E. Gross-Bermudex, G. A. Wilson, H. G. Wall, AND D. E. Dodd. TWO-WEEK INHALATION EXPOSURE OF RATS TO LIBBY AMPHIBOLE (LA) AND AMOSITE ASBESTOS. Presented at 50th Annual Society of Toxicology Meeting, Washington, DC, March 06 - 10, 2010.
Impact/Purpose:
Two week inhalation exposure to Libby amphibole causes equivalent or greater lung injury than a comparable concentration of amosite asbestos, in contrast to prior intratracheal instillation studies.
Description:
The relative potency of LA compared to UICC amosite was assessed in a subacute inhalation study designed to set exposure levels for a future subchronic study. Male F344 rats (n=7/group) were exposed nose-only to air (control), 3 concentrations of LA, or I concentration of amosite 6 hr/d, 5 d/wk, for 2 wk. Target and actual mean mass (mg/m3) concentrations were: air (0, 0.077); low (0.5, 0.56), medium (3.5, 3.52), and high (25, 28.23) LA; and amosite (3.5,3.67). There were no overt signs of toxicity during the study. One day after exposure, mean % neutrophils in bronchoalveolar lavage (BAL) fluid correlated well with exposure levels: control 0.8%; low (2.1%), medium (10.5%), and high (47.2%) LA; amosite 7.4%. BAL fluid protein, lactate dehydrogenase (LDH), alkaline phosphatase, and N-acetyl-B-D-glucosaminidase were significantly increased in the high LA group compared to control or amosite. LDH and protein in the medium LA group were significantly higher than either air or amosite. Four days after exposure, separate groups ofrats were evaluated for trachea and lung histopathology. The medium LA group had minimal to moderate alveolar inflammation which was slightly more severe than in the amosite group. Bronchiolar epithelial hyperplasia was observed in the high LA group. Minimal interstitial fibrosis was observed in the medium and high LA and amosite groups. Cell replication in terminal bronchioles assessed by BrdU was not consistently increased due to background focal inflammatory responses in 2 control and 2 low LA animals. Removal of these resulted in a LA concentration-related increase in cell replication. In contrast to prior intratracheal instillation studies (Padilla-Carlin et al., SOT 2009), inhalation exposure to the medium LA level caused equivalent or greater lung injury than a comparable concentration of amosite asbestos. (This abstract does not represent US EPA policy).