Pulmonary clearance and toxicity of intratracheally instilled cupric oxide in rats

Abstract

Pulmonary clearance and toxicity of cupric oxide (CuO) dusts, which are probably formed in refining and smelting factories, were investigated. Groups of three rats received intratracheal (i.t.) instillation of CuO at a dose of 20 micrograms Cu/rat in time-course experiments (up to 7 days post-instillation). Other groups of three rats received i.t. instillation of CuO at doses of 2.5, 5, 10, 30, 50 and 100 micrograms Cu/rat and were killed at 2 days post-instillation in dose-effect experiments. Intratracheally instilled CuO particles were cleared from the lung with a half-time of 37 h. Copper binding metallothionein (MT) was induced in a dose-dependent manner and detected at 12 h to 3 days post-instillation. Rapid clearance of CuO from the lung and induction of MT at 12 h post-instillation suggest that CuO particles were solubilized and then cleared from the lung. The acute pulmonary toxicity of CuO was evaluated by cytological (numbers of macrophages and polymorphonuclear leukocytes), biochemical and elemental inflammatory indices (lactate dehydrogenase and beta-glucuronidase activities and protein, sulfur, phosphorus and calcium contents) in the bronchoalveolar lavage (BAL) fluid. These inflammatory indices peaked at 12 h to 3 days post-instillation, and increased with dose over the dose range, except for phosphorus content. Dose-effect relationships in BAL inflammatory indicators of CuO-injected (i.t.) groups were compared to those of CuSO4-injected (i.t.) groups. The results of the comparison indicated that there was no significant difference in acute inflammatory potency between CuSO4 (soluble form of Cu) and CuO (insoluble form of Cu) in the rat lung.