Disposition of Inhaled Cadmium Oxide Aerosol in the Rat

Abstract

Male F344/N rats were exposed to target air concentrations of 0.0, 0.10, 0.25, or 1.0 mg CdO/m³ for approximately 6 h/day, 5 days/wk, for 13 wk. The lung burdens of Cd, the concentration of Cd in whole blood, and the concentration of Cd in the kidneys from exposure groups were determined at study days 3, 9, 30, and 93. Accumulated lung burdens were not directly proportional to the exposure concentration, but became progressively less than expected when exposure concentrations were increased. This was attributed to differences in exposure material deposition at different exposure concentrations, although the basis for these differences was not determined. Based on lung burden measurements made during the study, the lung clearance rate of Cd in F344 rats agreed well with values reported in the literature for Long-Evans and Wistar rats. Lung clearance half-lives did not change significantly with exposure concentration. Estimation of the deposition rate and the clearance rate constant allowed calculation of the equilibrium lung burdens expected in each of the exposure groups after long-term exposure. The concentration of Cd in blood was found to be very low in all exposure groups studied. Evidence suggests that the low blood concentration is most likely a result of rapid clearance from the blood to the kidney, and possibly the liver. The amount of Cd observed in the kidneys of exposed animals represented a significant fraction of the accumulated lung burden, and the concentration of Cd in the kidney was linearly proportional to the accumulated lung burden. Based on a linear model, projected accumulation of Cd in the kidneys of rats indicated that kidney Cd concentrations should be well below the toxic threshold when lung burdens reach steady state. However, this extrapolation will most likely underestimate accumulation of Cd in the kidney after steady-state lung burdens are achieved.