Uranyl Nitrate: 28-Day and 91-Day Toxicity Studies in the Sprague–Dawley Rat,

Gilman, Andrew P.; Villeneuve, D. C.; Secours, V. E.; Yagminas, Al; Tracy, B.L.; Quinn, J.M.; Valli, V. E.; Willes, R .J.; Moss, Michael A.

doi:10.1006/toxs.1997.2367

Cited by 64 publications

(69 citation statements)

References 16 publications

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“…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.…”

Section: Introductionmentioning

confidence: 99%

“…Alterations in the PT are reported to be most evident at the corticomedullary junction and include diffuse focal brush border loss, swollen mitochondria with loss of cristae, and increased vacuolization of the epithelial cells (17). Cellular necrosis ensues, resulting in cell membrane rupture and in discharge of cell contents in the lumen (14,22). Regeneration of PT cells is thought to occur just days after cessation of treatment with uranium; however, the new cells are different structurally and, presumably, functionally (2).…”

Section: Introductionmentioning

confidence: 99%

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

McDonald-Taylor¹,

Singh

Gilman

1997

Toxicol Pathol

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Naturally occurring uranium in drinking water is a significant health concern in several areas of North America. Because the kidney is a known target organ to examine the effects of uranium or its compounds, the objective of this study was to determine whether kidney repair occurs after exposure to, and withdrawal of, uranyl nitrate (UN). This work, part of a larger study to establish safe levels of uranium in drinking water supplies, examined the ultrastructural changes in proximal tubule cells of New Zealand white rabbits following subchronic exposure to UN in water and for 91 days after exposure ended. The rabbit was chosen as the experimental animal because of its high sensitivity to uranium. Animals were exposed to 24 or 600 mg UN per liter (UN/L) in drinking water for 91 days, with no recovery or recovery periods of 45 or 91 days. Ultrastructural changes, quantified by a stereological image anlysis system based on point counting, were observed in renal proximal tubules (PTs). Each electron micrograph was statistically considered an experimental unit. The severity of lesions was directly proportional to the dose. Animals exposed to 600 mg UN/L had the most severe lesions; nevertheless, alterations were remarkable in animals exposed to the low dose. At both recovery periods, the lesions were significantly more severe than those in animals of the no-recovery group, which may result from the kidney's ability to store uranium. The PT cells had increased lysosomal and vacuolar mass as well as variations in mitochondrial mass. In addition, there was epithelial cell degeneration with a focal loss of brush borders, thickening and splitting of tubular basement membrane, and occasionally cell necrosis. Interstitial fibrosis of the renal cortex persisted as the recovery period increased in the animals of UN-dosed groups. Alterations may be due to disturbed fluid transport across the PT and other cells and decreased cell respiration resulting from damaged cell constituents. Cell damage caused by UN in drinking water persisted throughout the 91-day recovery period. By eventually determining the no observable effect level for the kidney by UN, this study may assist in devising a model to ascertain the safe levels of uranium in water.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

McDonald-Taylor¹,

Singh

Gilman

1997

Toxicol Pathol

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“…Both functional and histologic damage to the proximal tubulus has been demonstrated (8)(9)(10)(11)(12)(13). Little is known about the effects of long-term environmental uranium exposure in humans.…”

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confidence: 99%

Renal effects of uranium in drinking water.

Kurttio

Auvinen²,

Salonen³

et al. 2002

Environ Health Perspect

388

211

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Animal studies and small studies in humans have shown that uranium is nephrotoxic. However, more information about its renal effects in humans following chronic exposure through drinking water is required. We measured uranium concentrations in drinking water and urine in 325 persons who had used drilled wells for drinking water. We measured urine and serum concentrations of calcium, phosphate, glucose, albumin, creatinine, and beta-2-microglobulin to evaluate possible renal effects. The median uranium concentration in drinking water was 28 microg/L (interquartile range 6-135, max. 1,920 microg/L) and in urine 13 ng/mmol creatinine (2-75), resulting in the median daily uranium intake of 39 microg (7-224). Uranium concentration in urine was statistically significantly associated with increased fractional excretion of calcium and phosphate. Increase of uranium in urine by 1 microg/mmol creatinine increased fractional excretion of calcium by 1.5% [95% confidence interval (CI), 0.6-2.3], phosphate by 13% (1.4-25), and glucose excretion by 0.7 micromol/min (-0.4-1.8). Uranium concentrations in drinking water and daily intake of uranium were statistically significantly associated with calcium fractional excretion, but not with phosphate or glucose excretion. Uranium exposure was not associated with creatinine clearance or urinary albumin, which reflect glomerular function. In conclusion, uranium exposure is weakly associated with altered proximal tubulus function without a clear threshold, which suggests that even low uranium concentrations in drinking water can cause nephrotoxic effects. Despite chronic intake of water with high uranium concentration, we observed no effect on glomerular function. The clinical and public health relevance of the findings are not easily established, but our results suggest that the safe concentration of uranium in drinking water may be within the range of the proposed guideline values of 2-30 microg/L.

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“…The destruction of liver tissue and induction of hematological disorders have also been shown in certain studies in laboratory animals [9,[29][30][31].…”

Section: Chemical Toxicitymentioning

confidence: 98%

Depleted Uranium and Its Effects on Humans

2015

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Abstract:The article summarizes contemporary scientific knowledge of depleted uranium effects on human health due to its use in military conflicts. The discussion covers cases of minimal risk due to external irradiation resulting from the storage and handling of depleted uranium ammunition and, in contrast, important toxicological and radio-toxicological risks of late effects resulting from the inhalation and ingestion of dust particles produced by the burning of the core of the anti-tank ammunition.

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Uranyl Nitrate: 28-Day and 91-Day Toxicity Studies in the Sprague–Dawley Rat,

Cited by 64 publications

References 16 publications

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

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

Renal effects of uranium in drinking water.

Depleted Uranium and Its Effects on Humans

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