US EPA

1424807 

Technical Report 

Inhalation of Uranium Oxide Aerosols: CNS Deposition, Neurotoxicity, and Role in Gulf War Illness 

Lewis, JL; Bench, G; Hahn, FF 

2003 

NTIS/02927065 

GRA and I 

GRA and I 

This proposal investigates the potential for inhaled uranium oxide (UO) aerosols to penetrate the nose-brain barrier, directly enter the central nervous system (CNS), diffusely distribute within the CNS, and result in slowly developing neurotoxic responses. Potentially substantial inhalation exposures to depleted uranium (DU) occurred during the GW and recent data suggests systemic DU enters the CNS and is associated with neurological deficits. Penetration of the nose-brain barrier can produce deposition of metals in the ONS that swamps concentrations seen in target organs of systemic deposition. Because several conditions during the war could have produced nasal inflammation, inflammation will be examined as a modifying factor that could result in increased sensitivity to uranium uptake via penetration of the nose-brain barrier. Nephrotoxic and pulmonary effects will be evaluated to determine whether CNS effects can occur at lower thresholds than nephrotoxic effects. To date, data have been analyzed from animals exposed to high concentration ((caret)500 mg/cu m) 15 minute exposures to uranium oxides varying in solubility, with or without prior endotoxin-induced inflammation. Under these conditions, female rats died of kidney toxicity within 2 weeks postexposure. Although uptake of uranium was generally not observed within the ONS, exposures were sufficient to produce neuroinflammation, with degree of inflammation positively associated with the solubility of the uranium oxide. 

Aerosols; *Central nervous system; *Neurotoxins; *Uranium compounds; Particle size; Toxicity; Proteins; Illness; Concentration(Composition); Nerve cells; Solubility; Inflammation; Depleted uranium; Endotoxins; Inhalation; Tantalum compounds; Persian gulf war; Uranium oxide