Domingo, JL; Llobet, JM; Tomás, JM; Corbella, J
The acute oral and subcutaneous toxicity of uranium (7440611) was investigated in rats and mice. Male Sprague-Dawley-rats and male Swiss-mice were administered single doses of uranyl-acetate (541093), subcutaneously or intragastrically. The median lethal dose (LD50) 14 days following subcutaneous administration was 8.3 and 20.4mg/kg for rats and mice, respectively; and the oral LD50 for rats was 204mg/kg and for mice was 242mg/kg. Most deaths occurred 5 to 8 days following uranyl-acetate administration. Physical signs of toxicity, usually evident after 6 days and persisting through the 14 day experimental period, included: weight loss, piloerection, rubefaction, tremors, hypotension, pupillary constriction, exophthalmos, and mild hemorrhages in eyes, nose, and legs. In a separate experiment, rats and mice were administered single doses of 210mg/kg uranyl-acetate subcutaneously or 10mg/kg intragastrically. Animals were observed for 14 days and then survivors were sacrificed and examined for pathological changes. Significant weight loss was observed in all treated animals. Food intake and amount of feces excreted were significantly reduced. Water consumption was not changed, but the volumes of urine excreted were significantly increased. Plasma urea and creatinine were significantly increased 7 days following either oral or subcutaneous uranyl-acetate administration. Histopathologic examination of the kidneys and liver revealed minimal lesions in animals administered uranyl-acetate orally, and more severe lesions in animals administered uranyl-acetate subcutaneously. The authors conclude that renal toxicity is the most characteristic response to uranyl-acetate, which is highly toxic when administered subcutaneously and moderately toxic when administered orally.