Lung injury in guinea pigs caused by multiple exposures to submicron zinc oxide mixed with sulfur dioxide in a humidified furnace.

Sulfur dioxide, water vapor, and ultrafine particles rich in oxides of zinc and other surface-deposited trace elements are important products of coal combustion. In order to study the toxicity of zinc oxide generated under conditions simulating combustion, guinea pigs were exposed in a nose-only apparatus for 3 h on 6 consecutive days to 6 mg/m3 of submicron zinc oxide particles (count median diameter of 0.05 micron, sigma g 2.0), which were generated in a humid furnace and mixed with 1 ppm sulfur dioxide. The exposures caused increases in lung weight and [3H] thymidine labeling index of terminal bronchiolar cell nuclei and inflammation of the proximal portion of the alveolar duct. The lung weights and labeling index had returned to normal and inflammatory changes had nearly resolved by 72 h after the last exposure. Total lung capacity, vital capacity, functional residual volume, alveolar volume, and diffusing capacity for carbon monoxide were decreased following exposure and had not returned to normal by 72 h after the last exposure. Large airways were not affected by the repeated exposures, as indicated by normal morphology of trachea and bronchi, unchanged secretory cell concentration, and unaltered epithelial permeability to horseradish peroxidase. These results are essentially identical to changes we reported in guinea pigs exposed to zinc oxide alone, suggesting that surface-deposited sulfur compounds, which are important determinants of the response to a single exposure to these ultrafine particles, become less important as exposure progresses.