Effects of aerosol exposures to cadmium chloride on the clearance of titanium dioxide from the lungs of rats.

This study deals with the hypothesis that the lymphatic uptake of particles from the lung parenchyma increases when phagocytosis by pulmonary macrophages is inhibited. Cadmium chloride was chosen as the toxicant to inhibit phagocytosis and was administered as an aerosol to rats at concentrations of 1.5 mg Cd/m3 (mass median aerodynamic diameter = 0.4 micron, sigma g = 1.4) and 5.0 mg Cd/m3 (MMAD = 0.4 micron, sigma g = 1.6), each for 30 min. Control animals were exposed to a saline aerosol. Lung clearance and lymphatic uptake were assayed after exposing the cadmium-exposed rats to titanium dioxide (TiO2) dust at concentrations of 12-15 mg/m3 (MMAD = 1.0 micron, sigma g = 2.3) for 6 h. Preexposure to 5 mg Cd/m3 decreased the initial deposition of TiO2 by 40% compared to a saline preexposure. Although the overall clearance of TiO2 from the lungs was not different in the cadmium-exposed animals, the lymph node burden was 2.7 times higher in the CdCl2-exposed animals than in the controls. Exposures to 1.5 mg Cd/m3 had no effect on lung clearance or lymphatic uptake of TiO2. When TiO2 exposure preceded a 5.0 mg Cd/m3 exposure, the results were similar; i.e., more TiO2 was found in the lymph nodes of the animals. This study supports the concept that lymphatic uptake of dust particles increases when phagocytosis by alveolar macrophages is decreased.