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© 1998 Oxford University Press

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Uranyl Nitrate: 91-Day Exposure and Recovery Studies in the Male New Zealand White Rabbit

A. P. Gilman*,1, M. A. Moss{dagger}, D. C. Villenuve*, V. E. Secours*, A. P. Yagminas*, B. L. Tracy*, J. M. Quinn*, G. Long* and V. E. Valli{ddagger}

*Environmental and Occupational Toxicology Division, Bureau of Chemical Hazards, Environmental Health Directorate, Department of National Health and Welfare Ottawa, Ontario Canada K1A 0L2 {dagger}Department of Pathology, Dalhousie University Halifax, Nova Scotia, Canada B3H 4H7 {ddagger}Department of Veterinary Pathobiology, University of Illinois at Urbana-Champaign Urbana, Illinois 61802

Received September 4, 1996; accepted September 2, 1997

This study was undertaken to examine the reversibility of renal injury in the male New Zealand White rabbit subsequent to a 91-day exposure to uranyl nitrate (UN) in drinking water, followed by various recovery periods. Specific pathogen-free (SPF) animals were exposed for 91 days to UN in their drinking water (24 or 600 mg UN/L). Control groups were given municipal tap water (<0.001 mg U/L). Regular clinical observations were recorded, and urine was collected periodically. Recovery periods between the last UN exposure and termination were 0, 8, 14, 45, or 91 days. Following the study, all animals were anesthetized and terminated by exsanguination, and multiple hematological and biochemical parameters were determined. Necropsies were conducted, and histopathological examination was performed. Exposure-related histopathological changes were observed only at much higher doses than in our previous male rabbit study where non-SPF-free animals had been used. Minor increases in kidney to body weight ratios were observed in the high-dose groups following exposure and early recovery. Renal tubular injury with degenerative nuclear changes, cytoplasmic vacuolation, and tubular dilation was seen in the high-dose group, without consistent resolution even after 91 days recovery. Animals ingested approximately 33% more uranium per day in this study than did males in a comparable dose group in the previous study, yet their kidney tissue uranium residues were 30% lower. These results suggest that SPF rabbits are less sensitive to uranyl injury than the non-SPF animals. The lowest-observed-adverse-effect level is estimated to lie at or below 24 mg UN/L.

Key Words: uranium; uranyl nitrate hexahydrate; subchronic exposure; drinking water; New Zealand; White rabbit; nephrotoxicity.


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