URANYL-NITRATE - 28-DAY AND 91-DAY TOXICITY STUDIES IN THE SPRAGUE-DAWLEY RAT

Although uranium (U) is a classic experimental nephrotoxin, there are few data on its potential long-term chemical toxicity. These studies w ere undertaken to derive a no-observed-adverse-effect level (NOAEL) in male and female Sprague-Dawley rats following 91-day exposure to uran ium (as uranyl nitrate hexahydrate, UN) in drinking water. Following a 28-day range-finding study, five groups of 15 male and 15 female wean ling rats were exposed for 91 days to UN in drinking water (0.96, 4.8, 24, 120, or 600 mg UN/L). A control group was given tap water (<0.001 mg U/L). Daily clinical observations were recorded. Following the stu dy, animals were euthanized and exsanguinated, and multiple hematologi cal and biochemical parameters were determined. Necropsies were conduc ted, and multiple tissues were sampled for histopathological examinati on. The hematological and biochemical parameters were not affected in a significant exposure-related manner. Although there were qualitative and slight quantitative differences between males and females, histop athological lesions were observed in the kidney and liver, in both mal es and females, in all groups including the lowest exposure groups. Re nal lesions of tubules (apical nuclear displacement and vesiculation, cytoplasmic vacuolation, and dilation), glomeruli (capsular sclerosis) , and interstitium (reticulin sclerosis and lymphoid cuffing) were obs erved in the lowest exposure groups. A NOAEL was not achieved in this study, since adverse renal lesions were seen in the lowest exposed gro ups. A lowest-observed-adverse-effect level of 0.96 mg UN/L drinking w ater can be reported for both the male and the female rats (average do se equivalent 0.06 and 0.09 mg U/kg body wt/day, respectively). (C) 19 98 Society of Toxicology.