Hirano S, Ebihara H, Sakai S, Kodama N, Suzuki K T
Environmental Health Sciences Division, National Institute for Environmental Studies, Ibarak, Japan.
Arch Toxicol. 1993;67(5):312-7. doi: 10.1007/BF01973701.
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.
对精炼厂和冶炼厂中可能形成的氧化铜（CuO）粉尘的肺部清除和毒性进行了研究。在时程实验中（滴注后长达7天），每组三只大鼠经气管内（i.t.）滴注剂量为20微克铜/只的CuO。在剂量效应实验中，其他每组三只大鼠经气管内滴注剂量为2.5、5、10、30、50和100微克铜/只的CuO，并在滴注后2天处死。经气管内滴注的CuO颗粒从肺中清除的半衰期为37小时。铜结合金属硫蛋白（MT）呈剂量依赖性诱导，并在滴注后12小时至3天检测到。CuO从肺中快速清除以及在滴注后12小时诱导MT表明CuO颗粒被溶解然后从肺中清除。通过支气管肺泡灌洗（BAL）液中的细胞学指标（巨噬细胞和多形核白细胞数量）、生化和元素炎症指标（乳酸脱氢酶和β-葡萄糖醛酸酶活性以及蛋白质、硫、磷和钙含量）评估CuO的急性肺毒性。这些炎症指标在滴注后12小时至3天达到峰值，除磷含量外，在整个剂量范围内随剂量增加而升高。将CuO注射（i.t.）组的BAL炎症指标的剂量效应关系与CuSO4注射（i.t.）组的进行比较。比较结果表明，在大鼠肺中，CuSO4（铜的可溶形式）和CuO（铜的不溶形式）之间的急性炎症效力没有显著差异。
