list-90 Revised (Derogatis 1983), the Beck Depression Inventory (Beck et al. 1996), the Beck Anxiety Inventory (Beck et al. 1988), and the Mississippi Scale for Posttraumatic Stress Disorder (Keane et al. 1988).

There were no statistically significant (p <0.05) differences between the high and low uranium-exposure groups in any neurocognitive measure at any of the five surveillance visits, although a higher impairment score on the A-IIac was consistently observed in the high-exposure group during the 1997 visits. For that time, results on the automated tests demonstrated a statistically significant relationship between urinary uranium concentration and lowered performance efficiency. More robust regression analyses that controlled for confounding factors, such as emotional status and general intellectual level, were conducted on A-IIac impairment scores from the 2001 and 2003 visits and urinary uranium concentrations. The results revealed a marginal association between measured urinary uranium and the accuracy index; however, the authors commented that the relationship in both years was driven by two cases with persistent complications due to combat injuries and their high urinary uranium concentrations (Hooper et al. 1999; McDiarmid et al. 2000, 2001a, 2004b, 2006).

Animal Studies

Description of morphologic changes in the central nervous system caused by exposure to uranium is limited to early experiments at high exposures. However, more recent studies with lower exposures have identified functional electrophysiologic effects and perhaps neuropsychologic (behavioral) effects. Studies performed many years ago showed that exposure of dogs to near-lethal doses of uranyl nitrate produced changes in the epithelium of the choroid plexus (Purjesz et al. 1930). In a more recent study that used an in situ brain-perfusion technique, Lemercier et al. (2003) showed that uranium reached the brain parenchyma by blood circulation (microcirculation) and the vascular space.

In a 30-d inhalation study, dogs exhibited muscular weakness and gait instability on day 13 of exposure to uranyl fluoride gas at a uranium concentration of 1.8 mg/m3 but showed no effects at lower concentrations (Dygert et al. 1949). In a study to determine the LD50, groups of 10 male Sprague-Dawley rats and 10 male Swiss mice were given a single subcutaneous dose of uranyl acetate at 1.25, 2.5, 5, 10, 20, and 50 mg/kg. The LD50 in rats was 8.3 mg/kg, and that in mice was 20.4 mg/kg. Rats and mice that survived 6 d or longer showed central cholinergic neurologic signs (piloerection, tremors, hypothermia, papillary size decrease, and exophthalmos) that persisted until termination of the study at 14 d (Domingo et al. 1987). The relevance of those studies to potential human exposure has been questioned (IOM 2000).

More recently, Pellmar et al. (1999a) surgically implanted DU pellets in the gastrocnemius muscle of rats at three doses (low dose, four DU and 16 tantalum pellets; medium dose, 10 DU and 10 tantalum pellets; and high dose, 20 DU pellets). After 1 mo, the uranium concentrations in the brain were statistically



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