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As described in Volume 1, skin absorption is an effective route for the entry of soluble uranium compounds into the systemic circulation. Substantial diffusion of soluble uranium through human or mammalian intact skin has been described (de Rey et al., 1983; Lopez et al., 2000; Tymen et al., 2000; Petitot et al., 2004).

Absorption of uranium via deep wounds has also been shown to depend on the solubility of the metal. Pellmar et al. (1999a) assessed distribution of uranium that was implanted in the gastrocnemius (lower leg) muscle of rats in the form of depleted-uranium pellets. A dose-dependent increase in uranium concentration was noted 1 day after implantation, reaching 82.0 ± 9.7 and 31.3 ± 6.5 ng of uranium per gram in the kidneys and tibias, respectively, of high-dose animals. Those concentrations were about 58 and 26 times higher than seen in the same tissues of the control group.

A recent study evaluated the influence of wounds on the short-term distribution and excretion of uranium in rats (Petitot et al., 2007). The authors reported substantial uptake of a uranyl nitrate solution through intact rat skin within the first 6 hours of exposure. Skin excoriation increased percutaneous absorption of uranyl nitrate, and this suggested that percutaneous diffusion of uranyl nitrate depends heavily on compromised skin-barrier integrity (Petitot et al., 2007). Similar studies with other forms of uranium were not found. However, in vitro studies corroborated greater diffusion of uranium through excoriated skin than intact skin; substantial uptake of uranium through excoriated skin occurred as early as 30 minutes after exposure (Petitot et al., 2004).

Transport and Biotransformation

Once absorbed, uranium forms soluble complexes with bicarbonate, citrate, or proteins in the plasma (Dounce, 1949; Stevens et al., 1980; Cooper et al., 1982). Little is known about the cellular and molecular mechanisms underlying the uptake of uranium in tissues. In the kidneys, a cytotoxic fraction of uranium was found to be a phosphate complex of uranyl whose uptake is mediated by a sodium-dependent phosphate cotransporter system (Muller et al., 2006). No other information on the mechanisms of transport could be found. The role of nonspecific metal transporters, such as divalent metal transporter-1, in the transport of uranium has yet to be defined.

Distribution

The percentages of uranium absorbed into blood, transferred to tissues, and excreted in urine are independent of the deposition of soluble uranium compounds, such as uranium peroxide or uranium tetrafluoride dust, in the lungs (Houpert et al., 1999). The ratio of K to (K + U), where K equals the percentage of uranium retained in the kidneys and U equals the percentage excreted in urine 24 hours after



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