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TOXICOKINETICS

The toxicokinetics of a substance has to do with the routes and rates of absorption, distribution, metabolism, and excretion. Toxicokinetics can be used to determine the amount of a substance that reaches particular organs or cells and might therefore lead to a toxic effect. For a review on biokinetic models of exposure to different forms of uranium with emphasis on depleted uranium, the reader may consult Leggett (2006).

Absorption

Where uranium particles are deposited in the respiratory tract is the result of a combination of physical forces that govern particle behavior in an air stream and the anatomy of the respiratory tract (Gordon and Amdur, 1991). The site of deposition affects the degree of uranium absorption, the clearance mechanisms that are available to remove uranium particles, and the severity of the consequences of damage of tissue of the respiratory system.

Which of the various regions of the respiratory tract and lung (extrathoracic, tracheobronchial, and deep pulmonary or alveolar) inhaled uranium-dust particles are deposited in depends on the particles’ aerodynamic diameter and inspiratory flow rate. An aerodynamic diameter that incorporates both the density and the diameter of particles and their aerodynamic drag is typically assigned to nonspherical particles. It represents a particle as having the diameter of a unit-density sphere that has the same terminal velocity as the particle, whatever its size, shape, or density (Gordon and Amdur, 1991). Larger particles are deposited in the tracheobronchial region; mucociliary action transports the particles to the pharynx, where they are swallowed. Smaller particles reach the terminal bronchioles and the alveoli. The International Commission on Radiological Protection has developed extensive models of the dosimetry of inhaled radioactive materials (ICRP, 2002).

At the alveolar level, the more soluble uranium compounds (categorized as type F for fast dissolution) are taken up by the systemic circulation within days. The less soluble uranium compounds (type M for medium dissolution) are likely to remain in the pulmonary tissue and associated lymph nodes for weeks. The relatively insoluble compounds (categorized as type S for slow dissolution) are least likely to enter the systemic circulation and may remain in the lung and tracheobronchial lymph nodes for several years (ATSDR, 1999). (See Table 3-1 for examples of uranium compounds of each type.) The lungs and the tracheobronchial lymph nodes are the two major sites of accumulation for type S uranium compounds (administered as uranium dioxide) in dogs, monkeys, and rats, accounting for greater than 90% of the total body burden of uranium after inhalation of the compounds (Leach et al., 1970).

Given their high density, most inhaled uranium-particle–containing dusts have an aerodynamic diameter that does not permit them to be carried to the



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