Distribution

Inhalation of less soluble uranium compounds (Type M and Type S) is associated with retention of uranium in bronchial lymph nodes as well as lung tissue itself (Leach et al., 1970), from which it passes slowly into the systemic circulation. Of the total uranium absorbed into the circulation, 85 percent deposits in the bone (Donoghue et al., 1972). Of the remaining uranium (15 percent), greater than 90 percent is distributed to the kidneys; detectable amounts are also present in the liver. In bone, uranium replaces calcium in the hydroxyapatite complex. The half-life of uranium in bone is approximately 300 days (Harley et al., 1999). In the kidney, uranium accumulates primarily in the proximal tubule.

Excretion and Retention

Systemic clearance. The stability of the bicarbonate complex of uranium depends on the pH of the solution and differs in various bodily compartments (Berlin and Rudell, 1986). The low-molecular-weight bicarbonate complex passes through the renal glomerulus and is excreted in the urine at a rate that depends on urinary pH. At high pH, small amounts of uranium are retained within the walls of the tubular lumen of the kidney. At low pH, bicarbonate– uranyl (and citrate–uranyl) complexes dissociate (Bassett et al., 1948). The uranyl ion forms complexes with proteins on the surface of cells lining the tubule, a process that may account for uranium-induced tubular dysfunction (see below). In contrast to the low-molecular-weight uranyl–bicarbonate complex, uranium that is protein bound is more likely to remain in blood since little protein passes through the glomerulus.

In humans, approximately two-thirds of an intravenous injection of uranium is eliminated from the plasma within 6 minutes, and 99 percent of the uranium is eliminated from the plasma 20 hours after injection (Struxness et al., 1956; Luessenhop et al., 1958). The kidneys excrete more than 90 percent of hexavalent soluble uranium salt injected intravenously, and less than 1 percent is excreted in the feces. Approximately 70 percent of the dose is excreted within the first 24 hours, followed by a slower phase with a half-time exceeding several months (Bassett et al., 1948).

Inhalation exposure. The rate of deposition and clearance of uranium-containing particles from the lung depends on their chemical form and particle size. As discussed above, mucociliary action transports most of the larger particles from the respiratory system to the pharynx, where they are swallowed and then eliminated in the feces. The clearance of the smaller particles that are deposited in the lungs depends on the solubility of the compounds. Particles that contain the more soluble forms of uranium are more rapidly absorbed into the bloodstream and excreted in urine. For example, in studies of rat lung retention of uranium administered as an aerosol powder (commercial yellowcake) with median aerosol concentrations from 0.04 to 0.34 μg U/L (micrograms of ura-



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