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Behavior of neutron-activated uranium dioxide dust particles in the gastrointestinal tract of the rat.

The behavior of neutron-irradiated, simulated Chernobyl UO2 particles containing 141Ce, 144Ce, 95Zr, 95Nb, and 103Ru in the gastrointestinal tract was investigated to obtain basic information for dosimetric and risk analyses of nuclear accidents. After the UO2 particles were administered to rats intragastrically, the distribution and retention of specific radionuclides were studied by using whole-body autoradiography and gamma-spectrometric analysis of tissues. None of the radionuclides were detected in liver, kidney, muscle, bone, brain, blood, and urine. Approximately 98% of the total administered radioactivity was excreted in feces within 3 days. A two times greater intestinal retention (about 6%) of 95Nb than for the other radionuclides was observed 1 day after administration. The results indicate that this kind of relatively insoluble particulate material is not absorbed or retained significantly in the epithelial cells of the intestinal wall. Fallout particles containing high-energy beta sources, 106Ru and 144Ce, result in a very high radiation dose (up to several Gy/day) in the vicinity of a hot particle. Niobium-95 with low average beta energy (0.043 MeV (100%)) does not increase the total dose to the GI tract significantly despite its longer retention in the intestine. Evaluation of the biological effects of these particles in the GI tract by using a dosimetric model based on uniform distribution of activity may be misleading.

Animals↗

An evaluation of Tiron (sodium 4,5-dihydroxybenzene-1,3-disulfonate) as a rescue agent for the nephropathy induced by uranyl fluoride (UO2F2) in rats.

Tiron (sodium 4,5-dihydroxybenzene-1,3-disulfonate) was tested as a potential rescue agent for the nephropathy induced by uranyl fluoride (UO2F2) in rats. When uranyl fluoride was administered (i.v.) to male Sprague-Dawley rats at a dose that delivered 250 micrograms U/kg, moderate to severe cellular necrosis occurred in pars recta segments of proximal tubules in the cortex and outer stripe of the outer medulla of the rats' kidneys within four days after treatment. The severity of renal tubular injury was not significantly diminished when rats were given a 10, 100 or 1,000 mg/kg dose of Tiron (i.p.) 30 minutes after the administration of uranyl fluoride. No obvious protection was noted even when the rats were given a 1,000 mg/kg dose of Tiron 15, 30 and 90 minutes after the administration of uranyl fluoride. Therefore, Tiron does not appear to provide rats substantial protection against a dose of uranyl fluoride that induces moderate to severe renal injury.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗

Renal handling of drugs in renal failure. I: Differential effects of uranyl nitrate- and glycerol-induced acute renal failure on renal excretion of TEAB and PAH in rats.

Two etiologically different models of experimental acute renal failure were induced in rats by administration of either glycerol or uranyl nitrate. Both compounds caused a substantial decrease in the glomerular filtration rate (GFR) and the net tubular secretion of tetraethylammonium bromide (TEAB) and para-aminohippuric acid (PAH). The degree of renal impairment induced by uranyl nitrate and glycerol appeared to be dose related. Deprivation of drinking water 24 hr before the administration of glycerol potentiated the renal damage. In uranyl nitrate-induced renal failure, the decline of the net tubular secretion for TEAB and PAH was not proportional to the decrease in GFR; the secretion process deteriorated faster than the GFR. For example, when 0.5 mg/kg uranyl nitrate was administered, GFR fell to approximately 65% of normal, whereas the net tubular secretion was decreased to 30% of normal. These results suggest that the tubular transport was preferentially affected by uranyl nitrate. In contrast, in glycerol-induced renal failure, the decline of TEAB secretion fell in a parallel fashion with the GFR, suggesting that the glomeruli and the proximal tubules were equally damaged by glycerol. However, in this latter model, the decline of PAH secretion did not parallel the decrease in GFR, contradicting the proposal that glycerol affects equally the glomeruli and the proximal tubules. This discrepancy may be due to the selective competitive inhibition of PAH secretion by the accumulation of naturally occurring organic acids.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

A World War II uranium hexafluoride inhalation event with pulmonary implications for today.

Two individuals were exposed to massive quantities of airborne uranium hexafluoride (UF6) and its hydrolysis products following a World War II equipment rupture. An excretion pattern for uranium exhibited by these patients is, in light of current knowledge, anomalous. The possible role of pulmonary edema is discussed. Examination of these individuals 38 years later showed no physical changes believed to be related to their uranium exposure and no deposition of uranium could be detected.

Accidents, Occupational↗

The spatial and temporal distribution of inhaled UO2 particles in the respiratory tract of the rat. I. Pulmonary tissue.

An analysis is described of the mass distribution of inhaled UO2 particles in the pulmonary tissue of rats by random sampling of fields in autoradiographs of histological sections. The degree of nonrandomness is compared between fields, between sections, and between lobes and interpreted in terms of the physical distribution of UO2. The error in the estimate of the mean number of charged-particle tracks from UO2 per field in the pulmonary tissue by selective tissue sampling is related to the degree of nonrandomness of the UO2 distribution. Estimates of this error in the lungs from nine animals range from 5.2 to 8.4%. When estimating this error, it is concluded that, in the case of the rat, sections should be taken at intervals of 3 mm or less throughout the lobes.

Animals↗

The spatial and temporal distribution of inhaled UO2 particles in the respiratory tract of the rat. II. The relative concentration of UO2 between the intrapulmonary airways and the pulmonary tissue.

In this experiment the relative masses of UO2 particles per unit mass of tissue are determined between intrapulmonary airways and pulmonary tissue in rat lungs. A mean value of 0.57 +/- 0.06 (SE) was determined in tissue sections taken at 3-mm or 5-mm intervals throughout the lobes of animals killed from 2 to 35 days after inhalation. The experimental results are compared with data derived from the ICRP Lung Model for man and indicate that in the rate approximately 4% of the lung burden as opposed to about 0.02% derived for man is associated with the intrapulmonary airways. The 4% figure, if also applicable to man, would have extremely important implications in radiological protection, since the basal cells of the bronchial epithelium are thought to be sensitive to the induction of bronchogenic carcinoma.

Animals↗

The clearance of uranium after deposition of the nitrate and bicarbonate in different regions of the rat lung.

This study investigated the tissue distribution and excretion of uranium after its deposition as either the nitrate or bicarbonate in the three regions of the respiratory system of the rat. Results confirm the recommendations of ICRP that uranyl nitrate and bicarbonate should be treated as class D compounds; but imply that some of the parameters used in the ICRP lung model are not applicable to soluble uranium compounds.

Animals↗

Synthesis and characterization of six new quaternary actinide thiophosphate compounds: Cs(8)U(5)(P(3)S(10))(2)(PS(4))(6)(,) K(10)Th(3)(P(2)S(7))(4)(PS(4))(2), and A(5)An(PS(4))(3), (A = K, Rb, Cs; An = U, Th).

Six new actinide metal thiophosphates have been synthesized by the reactive flux method and characterized by single-crystal X-ray diffraction: Cs(8)U(5)(P(3)S(10))(2)(PS(4))(6) (I), K(10)Th(3)(P(2)S(7))(4)(PS(4))(2) (II), K(5)U(PS(4))(3) (III), K(5)Th(PS(4))(3) (IV), Rb(5)Th(PS(4))(3) (V), and Cs(5)Th(PS(4))(3) (VI). Compound I crystallizes in the monoclinic space group P2(1)/c with a = 33.2897(1) A, b = 14.9295(1) A, c = 17.3528(2) A, beta = 115.478(1) degrees, Z = 8. Compound II crystallizes in the monoclinic space group C2/c with a = 32.8085(6) A, b = 9.0482(2) A, c = 27.2972(3) A, beta = 125.720(1) degrees, Z = 8. Compound III crystallizes in the monoclinic space group P2(1)/c with a = 14.6132(1) A, b = 17.0884(2) A, c = 9.7082(2) A, beta = 108.63(1) degrees, Z = 4. Compound IV crystallizes in the monoclinic space group P2(1)/n with a = 9.7436(1) A, b = 11.3894(2) A, c = 20.0163(3) A, beta = 90.041(1) degrees, Z = 4, as a pseudo-merohedrally twinned cell. Compound V crystallizes in the monoclinic space group P2(1)/c with a = 13.197(4) A, b = 9.997(4) A, c = 18.189(7) A, beta = 100.77(1) degrees, Z = 4. Compound VI crystallizes in the monoclinic space group P2(1)/c with a = 13.5624(1) A, b = 10.3007(1) A, c = 18.6738(1) A, beta = 100.670(1) degrees, Z = 4. Optical band-gap measurements by diffuse reflectance show that compounds I and III contain tetravalent uranium as part of an extended electronic system. Thorium-containing compounds are large-gap materials. Raman spectroscopy on single crystals displays the vibrational characteristics expected for [PS(4)](3)(-), [P(2)S(7)](4-), and the new [P(3)S(10)](5)(-) building blocks. This new thiophosphate building block has not been observed except in the structure of the uranium-containing compound Cs(8)U(5)(P(3)S(10))(2)(PS(4))(6).

Journal Article↗

Influence of uranium speciation on normal rat kidney (NRK-52E) proximal cell cytotoxicity.

Uranium is a naturally occurring heavy metal. Its extensive use in the nuclear cycle and for military applications has focused attention on its potential health effects. Acute exposures to uranium are toxic to the kidneys where they mainly cause damage to proximal tubular epithelium. The purpose of this study was to investigate the biological consequences of acute in vitro uranyl exposure and the influence of uranyl speciation on its cytotoxicity. NRK-52E cells, representative of rat kidney proximal epithelium, were exposed to uranyl-carbonate and -citrate complexes, which are the major complexes transiting through renal tubules after acute in vivo contamination. Before NRK-52E cell exposure, these complexes were diluted in classical or modified cell culture media, which can possibly modify uranyl speciation. In these conditions, uranium cytotoxicity appears after 16 h of exposure. The CI50 cytotoxicity index, the uranium concentration leading to 50% dead cells after 24 h of exposure, is 500 microM (+/-100 microM) and strongly depends on uranyl counterion and cell culture medium composition. Computer modeling of uranyl speciation is reported, enabling one to draw a parallel between uranyl speciation and its cytotoxicity.

Animals↗

Uptake of ingested uranium after low "acute intake".

The uptake of uranium, ingested as a soluble compound, was studied by monitoring the uranium level in urine by inductively coupled plasma mass spectrometry and through measurement of an isotopic tracer. The high sensitivity of this method allows measurement of uranium levels in urine samples from each voiding, therefore more detailed biokinetic studies are possible. To simulate low "acute intake," five volunteers with "normal" levels (5-15 ng L(-1)) of uranium in urine ingested a grapefruit drink spiked with 100 microg of uranium (235U/238U = 0.245%) as uranyl nitrate, and the level of uranium in their urine after ingestion was monitored. Two techniques were applied to estimate the extent of exposure: a) uranium levels above the normal level for each volunteer; and b) the deviation from natural isotopic ratio. Results were normalized relative to the creatinine concentration, which served as an indicator of urine dilution, to reduce effects due to diurnal changes. The results clearly indicate that currently accepted bio-kinetic models overestimate the time between ingestion of dissolved uranium and its excretion in urine, the maximum of which was found to be around 6-10 h. The uptake fraction was in agreement with recent studies, i.e., 0.1-0.5% of the ingested uranium for four of the subjects but above 1.5% for the fifth, and well below the 5% reported in International Commission on Radiation Protection Publication 54. Finally, partial results from the isotope dilution study indicate that uranium absorbed through the intestine interchanges with uranium retained in body organs. The time scale of this process is quite short, and the acute exposure led to a minimum in the isotopic ratio within hours, while recovery back to natural abundance due to low chronic exposure takes several days.

Adult↗

Uranyl nitrate-induced proximal tubule alterations in rabbits: a quantitative analysis.

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 analysis 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.

Animals↗

Scanning transmission electron microscopy at high resolution.

We have shown that a scanning transmission electron microscope with a high brightness field emission source is capable of obtaining better than 3 A resolution using 30 to 40 keV electrons. Elastic dark field images of single atoms of uranium and mercury are shown which demonstrate this fact as determined by a modified Rayleigh criterion. Point-to-point micrograph resolution between 2.5 and 3.0 A is found in dark field images of micro-crystallites of uranium and thorium compounds. Furthermore, adequate contrast is available to observe single atoms as light as silver.

Crystallography↗

Uranium(VI) sulfilimine complexes: a new class of nitrogen analogues of the uranyl ion.

The compound tetraphenylphosphonium tetrachlorooxo-S,S-diphenylsulfiliminatouranium, [Ph4P][UOCl4(NSPh2)], has been prepared in high yield from [Ph4P][UOCl5] and [Ph2S=NSiMe3]. An X-ray structure of this compound shows that the uranium atom has a pseudooctahedral geometry with oxygen and nitrogen atoms in trans positions. The structure of the analogous phosphoriminato complex [Ph4P][UOCl4(NPPh3)] has been determined for comparison. Derivatization of the sulfide group shows that only a limited range of functionalization confers stability toward reduction. The emission spectrum of the first electronic excited state reveals a greatly reduced energy compared with that of the uranyl ion. This red shift in the transition is consistent with the weakening of the U-N bond relative to the U-O bond.

Journal Article↗