Transition metals are components of airborne particles and have been implicated in adverse health effects. Relative toxicity and inflammatory potential of these metals are usually inferred from separate studies since little directly comparable data are available. The objective of this study was to compare the pulmonary effects of intratracheally-instilled, equimolar. soluble forms of six metal sulfates. Rats received either phosphate-buffered saline. 0.1 umol/kg, or 1.0 umol/kg of vanadium. nickel, iron (II), copper, manganese, or zinc. Bronchoalveolar lavage was performed at 0, 4, 16, or 48 hrs post-installation. At the 0.1 umol/kg dose, only Cu induced significant neutrophil influx at 16 and 48 hrs (p<0.05). For the 1.0 umol/kg dose at 4 hrs, Cu and Fe(II)-exposed animals had a significant increase in percent neutrophils compared to saline controls, and Cu had a significantly higher percentage than all other metals. After 16 hrs, each metal tested induced significant neutrophilia compared to controls, and Cu and Mn induced significantly higher neutrophilia than the other metals. At 48 hrs, neutrophilia was still increased in all metal exposures except Fe(II). Interestingly, Mn was the only metal to induce a significant increase in eosinophils (16 hr post-instillation, p<0.05). Additionally, Cu and Ni-exposed rats had significantly higher levels of lactate dehydrogenase in lavage supernatant compared to the other metals and controls. These results indicate that transition metals differ in their ability to induce pulmonary inflammation and toxicity. Cu appears to be the most pro-inflammatory metal, followed by Mn and Ni, while V, Fe(II), and Zn induced similar levels of neutrophilia. We conclude that the extent and cellular nature of metal-induced pulmonary inflammation depends on the individual metal.
The Toxicologist. Society of Toxicology 39th Annual Meeting, March 19-23, 2000, Philadelphia, Pennsylvania