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

Abstract

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.

Depleted and Natural Uranium: Chemistry and Toxicological Effects

“…In turn, Gilman et al (1998aGilman et al ( , 1998b, who examined rabbits that had been exposed to either 0.96, 4.8, 24, 120, or 600 mg/L uranyl nitrate hexahydrate for 91 d in drinking water, did not report adverse effects. Additionally, rats administered as much as 40 mg/kg/d of the same uranium compound in a drinking water vehicle for 28 d showed no signs of dose-dependent histopathological changes .…”

Données nouvelles sur la néphrotoxicité de l’uranium

“…Expérimentalement, après contamination chronique par voie orale (1 à 600 mg/L), différents paramètres urinaires (l'urée, le glucose, les protéines et l'albumine ainsi que les activités de LDH ou de NAG) ont été mesurés. L'hyperglucosurie semble être l'effet le plus persistant alors que les autres paramètres étudiés ne varient pas ou peu (Gilman et al, 1998a ;Ortega et al, 1989). A contrario, après exposition chronique via la mise en place d'implants sous-cutanés d'uranium, une augmentation des taux plasmatiques d'urée, de créatinine, d'albumine et de β2-microglobuline est observée (Zhu et al, 2008).…”

Uranyl Nitrate—Induced Proximal Tubule Alterations in Rabbits: A Quantitative Analysis

“…This study, part of a larger study with rats and rabbits to assess the effects of uranium in drinking water on a large number of physical, biochemical, and pathological parameters, was de-signed to determine the extent and reversibility of lesions in the proximal tubule of the kidney (12)(13)(14). Uranium has been recognized as a nephrotoxin since the late 1800s.…”