Pulmonary immunotoxicity of inhaled ammonium metavanadate in Fischer 344 rats.
Cohen-MD; Yang-Z; Zelikoff-JT; Schlesinger-RB
Fundam Appl Toxicol 1996 Oct; 33(2):254-263
The immunotoxic effects of acute, repetitive inhalation of pentavalent vanadium (7440622) in the rat lung were examined. Male Fischer-344-rats were exposed nose only to atmospheres of ammonium- metavanadate (7803556) (NH4VO3) at an occupationally relevant exposure level of 2mg/m3 as vanadium for 8 hours/day, for 4 days. Selected rats were killed immediately after each daily exposure, or 24 hours after the final exposure, for the analysis of lung burdens. The lungs were removed and prepared for graphite atomic absorption analysis. Immunotoxic effects were assessed by analysis of isolated rat pulmonary alveolar macrophages (PAMs), a tumor necrosis factor- alpha (TNF-alpha) production assay, measurements of ROI production in recovered lung cells, assessments of interferon gamma (IFN-gamma) induced I-A expression, and phagocytic activity of recovered cells. Lung analysis showed that inhalation of NH4VO3 at the studied exposure levels produced a significant time dependent increase in lung burden, with increases of 44% between the first 2 days of exposure, and 10% increases after that time. Exposed rats also exhibited increases in the absolute numbers and relative percentages of neutrophils and small macrophages. Significant increases in lactate-dehydrogenase activity and protein levels in the bronchoalveolar fluid suggested lung cell damage due to vanadium exposure. vanadium exposure also substantially inhibited the capacity of PAMs to generate TNF-alpha and ROI, actively phagocytize opsonized particles, and increase the surface expression of I-A antigen. The study results indicated that host pulmonary immunocompetence in rats can be altered by short term, repeated exposure to vanadium at occupationally relevant levels, with effects on cytokine related functions. The authors conclude that such changes may explain the documented increases in lung infections and cancers in workers with long term exposures to vanadium.
NIOSH-Publication; NIOSH-Grant; Grants-other; Laboratory-animals; Vanadium-compounds; Pulmonary-system; Toxic-effects; Immune-reaction; Lung-tissue; Immune-system; Lung-burden
Environmental Medicine New York University Med Center 550 First Ave New York, NY 10016
Other Occupational Concerns
Fundamental and Applied Toxicology
New York University, New York, New York