Metabolism and pulmonary toxicity of intratracheally instilled cupric sulfate in rats.

Though copper (Cu)-handling workers are known to be at risk to develop metal fume fever and acute respiratory failure, very little is known about the metabolic fate and pulmonary toxicity of Cu compounds deposited in the lung. We have investigated time-course and dose-related changes in Cu contents, the production of metallothionein (MT) and inflammatory responses in the rat lung following intratracheal instillation of cupric sulfate (CuSO4). Intratracheally instilled Cu was cleared rapidly from the lung with a half-time of 7.5 h. Copper-binding MT was induced in the lung tissue following Cu instillation and the amount of MT increased with the dose of CuSO4. However, the production of MT contributed little to the accumulation of Cu in the lung. The pulmonary toxicity of CuSO4 was evaluated by examining time-course and dose-effect profiles of cytological and biochemical inflammatory indices (enzymes, protein and elements) retrieved in bronchoalveolar lavage fluids. These results revealed that the inflammatory indices reached maximum values in their activities and contents at 12 h to 3 days after instillation and a dose of 5 micrograms Cu/rat was sufficient to produce acute inflammatory responses in the rat lung.