Effects of Phosgene Exposure on Bacterial, Viral, and Neoplastic Lung Disease Susceptibility in Mice

Abstract

In this study the effects of phosgene inhalation on host resistance models representative of bacterial, viral, and neoplastic lung diseases were assessed. A single Ch exposure to concentrations of phosgene of 0.025 ppm and above significantly enhanced mortality due to laboratory-induced aerosol infection with Streptococcus zooepidimi-cus (group C). Bacteria recovered from lavage fluid of mice exposed to 0.05 ppm for 4 h increased dramatically between 3 and 48 h post infection, while bacteria recovered from lavage fluid of air exposed mice declined to nearly undetectable levels over the same time period. Concentrations of phosgene 10-fold higher than the lowest observable effect concentration for streptococcus susceptibility had little or no effect on alveolar macrophage phagocytic activity and little or no effect on total cells recovered, viability, or differential cell counts in lavage fluid obtained shortly after exposure. A single 4-h exposure to as little as 0.025 ppm phosgene also caused a significant increase in the number of B16 melanoma tumors that developed in the lungs of mice following intravenous inoculation of syngeneic tumor cells. In contrast, 5 daily 4-h exposures to 0.5 ppm phosgene had no effect on mortality following infection with influenza virus and only minimal effects on lung virus titers. When exposure time was increased from 4 to 8 h, significant effects on mortality due to streptococcus infection were observed at an exposure concentration of 0.01 ppm. However, increasing the exposure time from 4 to 8 h did not alter the lowest observable effect concentration (0.025 ppm) for the 816 tumor model. The data indicate that exposure to phosgene concentrations equal to 10–25% of the current threshold limit value (0.1 ppm) significantly enhanced susceptibility to bacterial and tumor disease in mice. In contrast, the concentrations of phosgene used in this study had little effect on the influenza virus infection.