Comparative pulmonary toxicity of various soluble metals found in urban particulate dusts

The potential toxicity of an atmospheric dust sample EHC-93 has been attributed to the soluble fraction and, more specifically, to the zinc component. The concentration of Zn is the highest among the metals present in the soluble EHC-93 fraction. We now determine whether other metal components of this dust could cause similar lung injury if present at the same concentration as Zn (4.8 mg/g dust). Solutions of Zn, Cu, V, Ni, Fe, and Pb salts in 0.1 mL water were instilled to mouse lung and animals were killed at intervals up to 2 weeks later; each mouse received tritiated thymidine 1 hour before death. Solutions containing Zn and to a lesser degree Cu induced lung injury; in addition, increased numbers of alveolar macrophages and polymorphonuclear leukocytes were found in the lavage fluid, which also contained increased protein levels up to 1 week later. The magnitude of response was similar to that seen after administering EHC-93 dust at 1 mg in 0.1 mL water, whereas the response to other metal solutions containing Ni, Fe, Pb, and V was minimal. Morphologic evidence of lung injury and inflammation was also seen after EHC dust and the Zn or Cu solutions only. Reparative cell proliferation was measured after thymidine uptake and autoradiographs showed increased labeling of lung cells, particularly at 3 and 7 days. Labeling was confined to bronchiolar and type 2 alveolar epithelial cells, indicating previous epithelial cell necrosis in response to Zn or Cu. The results indicate that atmospheric contaminant metals Zn and Cu are most likely to cause lung injury and inflammation as compared to metals such as Ni, Fe, Pb, and V at the same concentrations. It appears that similar toxicity occurs when both redox (Cu) and nonredox (Zn) reactions are involved.