© 1998 Oxford University Press
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Uranyl Nitrate: 28-Day and 91-Day Toxicity Studies in the Sprague-Dawley Rat1
*Environmental Health Directorate, Department of Health Ottawa, Ontario, Canada K1A 0L2
Department of Veterinary Pathobiology, University of Illinois at Urbana-Champaign Urbana, Illinois 61802
F. D. C. Consultants, Inc. Orono, Ontario, Canada LOB 1M0
Department of Pathology, Dalhousie University, Halifax Nova Scotia, Canada B3H 4H7
Received September 4, 1996; accepted September 2, 1997
Although uranium (U) is a classic experimental nephrotoxin, there are few data on its potential long-term chemical toxicity. These studies were undertaken to derive a no-observed-adverse-effect level (NOAEL) in male and female Sprague-Dawley rats following 91-day exposure to uranium (as uranyl nitrate hexahy-drate, UN) in drinking water. Following a 28-day range-finding study, five groups of 15 male and 15 female weanling 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 study, animals were euthanized and exsanguinated, and multiple hematological and biochemical parameters were determined. Necropsies were conducted, and multiple tissues were sampled for histopathological examination. 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, histopathological lesions were observed in the kidney and liver, in both males and females, in all groups including the lowest exposure groups. Renal lesions of tubules (apical nuclear displacement and vesiculation, cytoplasmic vacuolation, and dilation), glomeruli (capsular sclerosis), and in-terstitium (reticulin sclerosis and lymphoid cuffing) were observed in the lowest exposure groups. A NOAEL was not achieved in this study, since adverse renal lesions were seen in the lowest exposed groups. A lowest-observed-adverse-effect level of 0.96 mg UN/L drinking water can be reported for both the male and the female rats (average dose equivalent 0.06 and 0.09 mg U/kg body wt/day, respectively).
Key Words: uranium; uranyl nitrate hexahydrate; subchronic exposure; drinking water; Sprague-Dawley rat; nephrotoxicity.
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