Pulmonary clearance and toxicity of zinc oxide instilled into the rat lung

Pulmonary toxicity of zinc oxide (ZnO) was evaluated by investigating the metabolic fate and inflammatory potency of ZnO instilled into the rat lung. Groups of three rats received single intratracheal instillations of ZnO suspension at a dose of 100 micrograms Zn/rat in the time-course experiment or received 20, 50, 100, 200, 500 and 1000 micrograms Zn/rat and were killed 2 days after treatment in the dose-response experiment. It was suggested that ZnO particles were solubilized in the bronchoalveolar milieu and cleared from the lung with a half-life of 14 h. Metallothionein (MT) was induced with a peak at 2 days. The content of MT was proportional to the dose of ZnO, but contributed little for the accumulation of Zn in the lung. A dose of 20 micrograms Zn/rat was sufficient to develop maximum responses for beta-glucuronidase activity and surfactant content in the bronchoalveolar lavage fluid. Moreover, the activity of lactate dehydrogenase and protein content in the lavage fluid increased significantly at 20 micrograms Zn/rat. These results suggest that the recommended ZnO concentration in the work-place atmosphere of 5 mg/m3 might not be adequate.