and substances, including neurotransmitters and peptides, are known to modulate REM sleep; the underlying mechanisms for these changes remain unknown.

Using a similar exposure paradigm (1-month exposure to depleted uranium at 40 mg/L in drinking water), the same group of investigators examined dopamine and serotonin brain metabolism in the rat (Houpert et al., 2004). No statistically significant differences were found in dopamine, serotonin, and their catabolite levels in the striatum, hippocampus, cerebral cortex, thalamus, or cerebellum between depleted uranium-exposed and control rats. Thus, it appears that depleted uranium-induced changes in the sleep-wake cycle are not mediated by dopamine and serotonin. Other neurotransmitters might be involved, or, given the role of the hypothalamic-pituitary axis in sleep regulation, these effects may be modulated by glucocorticoids. Bussy et al. (2006) investigated effects of exposure to depleted uranium (as uranyl nitrate) in drinking water at 40 mg/L for up to 9 months on dopaminergic and serotoninergic metabolism in rats and found subtle and transient perturbations of monoamine concentrations and AChE activity in discrete brain areas.

Collectively, the results of those studies indicate that depleted uranium is a toxicant that can cross the blood-brain barrier and might produce some acute and prolonged behavioral changes. The mechanisms associated with the effects are difficult to reconcile, given the differences in exposure models and apparent contradictions in the results: some studies established a treatment effect and others failed to. Although at high concentrations different forms of uranium might be associated with some subtle neurologic dysfunction, the significance of the observations is unknown.

Absorption of ingested uranium occurs mainly in the small intestine (ICRP, 1979). The chemical form of uranium in ingested water does not appear to influence absorption from the gastrointestinal tract in rats (Frelon et al., 2005). No animal or in vitro studies on the effects of uranium-induced pathology in the gastrointestinal tract could be found since those described in Volume 1. As summarized in Volume 1, studies have suggested that up to 2-year exposure of various animal species to high doses of uranium nitrate is not associated with gastrointestinal effects. Studies that used other forms of uranium could not be found.

Uranium-induced hepatotoxicity has not been a prominent finding in most animal studies (ATSDR, 1999). A few studies of hepatotoxicity have been published since Volume 1; the experimental details are summarized in Table 3-7.