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Uranium in vitro bioassay action level used to screen workers for chronic inhalation intakes of uranium mill tailings.

A uranium in vitro bioassay (urinalysis) action level was derived for use at the Department of Energy's Uranium Mill Tailings Remedial Action Project sites to identify chronic inhalation intakes of uranium mill tailings causing 0.5 mSv (50 mrem) annual effective dose equivalent. All radionuclides in the 238U decay chain that contribute 1% or more to the annual effective dose equivalent from an inhalation intake of uranium mill tailings were included in the derivation of the urinalysis action level. Using a chronic inhalation intake model, the uranium urinalysis action level for a 24-h urine sample, collected on a quarterly schedule, was calculated to be 1.5 micrograms.

Humans

[Uranium, thorium and potassium contents and radioactive equilibrium states of the uranium and thorium series nuclides in phosphate rocks and phosphate fertilizers].

Uranium, thorium and potassium contents and radioactive equilibrium states of the uranium and thorium series nuclides have been studied for 2 phosphate rocks and 7 phosphate fertilizers. Uranium contents were found to be rather high (39-117 ppm) except for phosphate rock from Kola. The uranium series nuclides were found to be in various equilibration states, which can be grouped into following three categories. Almost in the equilibrium state, 238U approximately 230Th greater than 210Pb greater than 226Ra and 238U greater than 230Th greater than 210Pb greater than 226Ra. Thorium contents were found to be, in general, low and appreciable disequilibrium of the thorium series nuclides was not observed except one sample. Potassium contents were also very low (less than 0.3% K2O) except for complex fertilizers. Based on the present data, discussions were made for the radiation exposure due to phosphate fertilizers.

Alpha Particles

Uranium-loaded apoferritin with antibodies attached: molecular design for uranium neutron-capture therapy.

A method is described to deliver 235U to tumors; the isotope would then be fissioned by incident neutrons, producing localized lethal radiation sufficient for therapy. Apoferritin was loaded with an average of approximately 800 238U atoms per molecule. Stability of the loaded apoferritin in solution was improved, so that only 8% loss of uranium occurred after 8 days at pH 7. Fab' antibody fragments were covalently attached to the uranium-loaded apoferritin, and the immunoreactivity of the conjugate was 92% of that for antibody alone. Such bio-uranium constructions should provide significant advantages over boronated antibodies to meet the requirements for clinical neutron-capture therapy.

Apoferritins

Increased deposition of uranium in the bones of vitellogenic male Japanese quail. Effect of estradiol-17 beta on the distribution of uranium (VI), thorium (IV), gadolinium (III), and calcium (II).

Japanese quail were given, intramuscularly, either 16-mumol estradiol-17 beta (E2) in .25-ml ethanol solution/100 g body weight or .25 ml ethanol/100 g. Four days later, these quail were given, intravenously, 1.5-mumol UO2(NO3)2, Th(NO3)4, GdCl3 (153Gd-labeled) or CaCl2 (47Ca-labeled)/.15 ml .03 N HCl solution/100 g. The distribution of uranium among selected tissues was markedly different than for thorium or gadolinium and was approximately the same as for calcium. For example, 18 hr after giving the metal ions to the quail, the mean uranium content of the femora + tibiotarsi of E2-treated males was 15.4 +/- 1.3% (SE; n = 12) vs. 3.07 +/- .59% (12; P less than .001) for the control males. Similarly, 18 hr after giving calcium, the femora + tibiotarsi of E2-treated males had accumulated 20.8 +/- 1.5% (4) of the label vs. 9.94 +/- .46% (4; P less than .001) for controls. The livers of E2-treated males had 41.9 +/- 8.5% (4) of the thorium by 18 hr vs. 90.9 +/- 7.1% (4; P less than .01) for the controls, or 34.3 +/- 3.1% (8) of the gadolinium vs. 68.9 +/- 3.4% (8; P less than .001) for controls. The 18-hr accumulation of calcium in the femora + tibiotarsi of the E2-treated females was 18.0 +/- 1.1% (4) vs. 10.7 +/- 1.9% (4; P less than .05) for the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effectiveness of chelation therapy with time after acute uranium intoxication.

The effect of increasing the time interval between acute uranium exposure and chelation therapy was studied in male Swiss mice. Gallic acid, 4,5-dihydroxy-1,3- benzenedisulfonic acid (Tiron), diethylenetriaminepentaacetic acid (DTPA), and 5-aminosalicylic acid (5-AS) were administered ip at 0, 0.25, 1, 4, and 24 hr after sc injection of 10 mg/kg of uranyl acetate dihydrate. Chelating agents were given at doses equal to one-fourth of their respective LD50 values. Daily elimination of uranium into urine and feces was determined for 4 days after which time the mice were killed, and the concentration of uranium was measured in kidney, spleen, and bone. The excretion of uranium was especially rapid in the first 24 hr. Treatment with Tiron or gallic acid at 0, 0.25, or 1 hr after uranium exposure significantly increased the total excretion of the metal. In kidney and bone, only administration of Tiron at 0, 0.25, or 1 hr after uranium injection, or gallic acid at 1 hr after uranium exposure significantly reduced tissue uranium concentrations. Treatment at later times (4 to 24 hr) did not increase the total excretion of the metal and did not decrease the tissue uranium concentrations 4 days after uranyl acetate administration. The results show that the length of time before initiating chelation therapy for acute uranium intoxication greatly influences the effectiveness of this therapy.

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

Uptake of uranium by various cell fractions of Chlorella regularis.

To know what kinds of the cell components of Chlorella regularis are concerned with uranium binding, uptake of uranium by various cell fractions was examined. The uptake value (microgramU/mg starting dry cells) of the hot water-treated cells was almost the same as that of the starting dry Chlorella cells, showing that the cell components extracted with hot water were not so concerned with uranium binding. The cell components extracted with dilute alkali seemed to play an important role in uranium binding, and those extracted with chloroform-methanol seemed to be partly concerned with uranium binding. The cellulose fraction of the cells was scarcely concerned with uranium binding. In the dry cells, 34% of uranium taken up existed in the cell walls. However, in the living cells, 85% existed in the cell walls. The above results showed that the dry or the hot water-treated cells are the most convenient for uranium recovery from the aqueous systems.

Chlorella

Bacterial leaching of waste uranium materials.

The effect of ferrobacteria and thiobacteria on the leaching of waste uranium materials from which 70-80% of uranium was previously leached by classical chemical hydrometallurgical procedure has been investigated. The bacteria used are found in the ore and the mine water of Zletovska River locality, Yugoslavia. Parameters of biological leaching were examined in the laboratory. Leaching conditions were changed with the aim of increasing the amount of uranium leached. The effect of pyrite added to the waste materials before the beginning of leaching has also been examined. Uranium leaching is directly proportional to the composition and number of ferrobacteria and thiobacteria, and increased by almost twice the value obtained from the same starting materials without using bacteria. Increased sulphuric acid concentrations stimulate considerably the rate of leaching. Uranium leaching is increased up to 20% while sulphuric acid consumption is simultaneously decreased by the addition of pyrite. Uranium concentrations in starting waste materials used for leaching were extremely low (0.0278 and 0.372% U) but about 60% recovery of uranium was obtained, with relatively low consumption of sulphuric acid.

Acidithiobacillus thiooxidans

Metabolism of uranium in the rat after inhalation of two industrial forms of ore concentrate: the implications for occupational exposure.

Aerosols produced from two commercially available ore concentrates in which the uranium was present essentially in the one as ammonium diuranate (ADU) and in the other as uranium octoxide (U3O8) were administered to rats. The results show that: 1 uranium in the ADU bearing material was cleared rapidly from the lungs, mainly to the blood, such that the retention kinetics were similar to those for a class D (highly transportable) compound as defined by ICRP; 2 uranium in the U3O8 bearing material was removed from the lungs principally by mechanical processes, the retention kinetics in this case being similar to those defined for a class Y (poorly transportable) compound; 3 for both materials the distribution of uranium amongst body tissues and the fraction of the systemic content excreted in urine were similar to those obtained after the injection of soluble hexavalent compounds; 4 for workers potentially exposed to both these materials, urine monitoring and lung radioactivity counting measurements should be used in addition to air sampling procedures for assessing the intake of uranium. 5 intakes of the ADU bearing material should be restricted to those permitted for short-term exposures on the basis of chemical toxicity, whereas those for the U3O8 bearing material should be governed by radiation dose.

Aerosols

Influence of chronic exposure to uranium on male reproduction in mice.

Relatively few data are available concerning the reproductive and developmental toxicity of uranium. The present study was designed to evaluate the reproductive effects of this metal in male Swiss mice. The animals were treated with uranyl acetate dihydrate at doses of 0, 10, 20, 40, and 80 mg/kg/day given in the drinking water for 64 days. To evaluate the fertility of the uranium-treated males, mice were mated with untreated females for 4 days. There was a significant but non-dose-related decrease in the pregnancy rate of these animals. Body weights were significantly depressed only in the 80 mg/kg/day group. Testicular function/spermatogenesis was not affected by uranium at any dose, as evidenced by normal testes and epididymis weights and normal spermatogenesis, whereas interstitial alterations and vacuolization of Leydig cells were seen at 80 mg/kg/day. The results of this investigation indicate that uranium does not cause any adverse effect on testicular function in mice at the concentrations usually ingested in the diet and drinking water, with a safety factor of more than 1000. However, although spermatogenesis was not affected by uranium administration, uranium produces a significant decrease in the pregnancy rate at 10, 20, 40, or 80 mg/kg/day.

Animals

Determining the normal concentration of uranium in urine and application of the data to its biokinetics.

A method was developed to determine the concentration of uranium (238U) in urine. This method involved preconcentration of uranium from urine with calcium phosphate neutron activation followed by simple radiochemical separation. Using this method, it was possible to detect 0.2 ng of 238U. The average and geometric mean concentration of uranium found in urine of subjects from a normal background environment was 12.8 and 9.4 ng L-1, respectively. The concentration of uranium in the urine and the daily intake of uranium by the same population was used to arrive at the gastrointestinal absorption factor (f1) for uranium incorporated in the diet. The f1 factor was estimated to be 1.6%.

Adult

In vitro dissolution of uranium oxide by baboon alveolar macrophages.

In vitro cellular dissolution tests for insoluble forms of uranium oxide are technically difficult with conventional methodology using adherent alveolar macrophages. The limited number of cells per flask and the slow dissolution rate in a large volume of nutritive medium are obvious restricting factors. Macrophages in suspension cannot be substituted because they represent different and poorly reproducible functional subtypes with regard to activation and enzyme secretion. Preliminary results on the dissolution of uranium oxide using immobilized alveolar macrophages are promising because large numbers of highly functional macrophages can be cultured in a limited volume. Cells were obtained by bronchoalveolar lavages performed on baboons (Papio papio) and then immobilized after the phagocytosis of uranium octoxide (U3O8) particles in alginate beads linked with Ca2+. The dissolution rate expressed as percentage of initial uranium content in cells was 0.039 +/- 0.016%/day for particles with a count median geometric diameter of 3.84 microns(sigma g = 1.84). A 2-fold increase in the dissolution rate was observed when the same number of particles was immobilized without macrophages. These results, obtained in vitro, suggest that the U3O8 preparation investigated should be assigned to inhalation class Y as recommended by the International Commission on Radiological Protection. Future experiments are intended to clarify this preliminary work and to examine the dissolution characteristics of other particles such as uranium dioxide. It is recommended that the dissolution rate should be measured over an interval of 3 weeks, which is compatible with the survival time of immobilized cells in culture and may reveal transformation states occurring with aging of the particles.

Animals

Determination of uranium in human teeth, bones and tissues by the fission track method.

The uranium content of several human tooth, bone and soft tissue samples was determined by the fission tract method. The average uranium content in teeth, bones and soft tissues were 6.7, 8.4 and 64 ppb ash, respectively. The distribution of uranium in bones is less uniform than that of teeth, and the uranium content of soft tissues is generally higher than that of teeth and bone. The presence of thorium does not interfere with the uranium determination in most cases.

Bone and Bones

Uranium and lead accumulation in cells of Streptomyces sp.

Lead and uranium were accumulated equally well both in the viable and dry biomass of Streptomyces sp. The process occurred in less than 5 min. Uranium was accumulated selectively from a polymetallic solution containing U, Pb, Cu, Zn, Ni, Co. The optimum pH for the process was 5.0, and the concentration of each metal in the solution was 10(-3) M. Under these conditions, the dry biomass of Streptomyces amounting to 1 mg/cm3 accumulated over 60% of the uranium in the solution. With the same amount of cell wall preparation it was possible to remove from the solution ca. 90% of U. In this case, the accumulated uranium reached 21% of the sorbent dry mass. Electron micrographs show that lead accumulated in Streptomyces cells is mainly concentrated in the cell wall structures although in the case of uranium this is not so clear.

Hydrogen-Ion Concentration

Cytotoxic effect of uranium dioxide on rat alveolar macrophages.

Alveolar macrophages obtained by bronchial lavage were used to assess the response of these cells to cultivation in media containing increasing concentrations of particulate UO2. The characteristic time course of uranium effects on alveolar macrophages was determined by analyzing cell viability and incorporation of uranium particles. This study reveals the ability of alveolar macrophages to phagocytize uranium particles despite the high toxicity the metal exerts on cell membranes. However, lethal effects soon become evident. Ultrastructural analysis showed uranium particles confined within membrane bound vacuoles or free in the cytoplasm. Marked ultrastructural alterations consistent with cell death were frequently observed. The elimination of the first biological barrier hinders the scavenging of particulate contaminants in alveolar spaces, thus favoring the translocation to target organs.

Animals

Lung dissolution of uranium tetrafluoride in rats and baboons. Comparison with dissolution by alveolar macrophages in culture and chemical dissolution.

Lung dissolution of industrial uranium tetrafluoride (UF4) was tested in rats and baboons by intratracheal instillation and inhalation, to check the W classification given to UF4 by the International Commission on Radiological Protection. Rats and baboons were given 10 and 160 micrograms of UF4 per animal respectively. Lung clearance, urinary excretion and tissue distribution of uranium were measured in rats, and urinary excretion was measured in baboons. After intratracheal instillation, daily urinary excretion was fast in both species; 4.8 +/- 0.7 X 10(-2) of the initial lung burden (ILB) in rats and 2.9 +/- 0.3 X 10(-2) in baboons. After inhalation of dry UF4 powder, daily urinary excretion was 5.6 +/- 2.2 X 10(-2) of the ILB in rats and the lung clearance half-life was 7.3 d. The amounts of uranium excreted by rats and baboons were compared to the amounts dissolved in vitro by alveolar macrophages from both species, and also to the amount dissolved chemically by a serum simulant. Both rat and baboon macrophages were clearly shown to be involved in the mechanism of uranium dissolution, since on the first day of macrophage culture, they dissolved 20 and 40% respectively of the amounts of UF4 added to the macrophage cultures, again illustrating the fast dissolution of UF4.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation

[Thorium amd uranium in food of animal origin].

The thorium and uranium contents (alpha-activities of the natural isotopes Th-228, Th-230, Th-232, U-234, and U-238) in several samples of the meat of domestic animals, venison, and cold-blooded animals are reported. The activity of thorium and of uranium was surprisingly constant in lean meat of all the animals tested. The average activity of the main isotope of thorium was 1-2 mBq Th-232/kg fresh meat (FM) and of uranium 21-34 mBq U-238/kg FM. The lowest and highest values observed were 0.4 and 2.7 mBq Th-232/kg FM, and 9 and 41 mBq U-238/kg FM, respectively. In some internal organs distinctly higher values were obtained: 8.6 mBq Th-232/kg in cattle bones, and 51 mBq U-238/kg in hog kidneys. The highest content of U-238, 84 mBq/kg, was observed in cuttlefish (whole animal). In lean meat, the activity of the daughter isotope Th-228 was on average (by factor) two to four times higher than that of the parent isotope Th-232. In cattle bones, and in fish samples including bones, the factor was 20 and 26, respectively. The activity of the isotope Th-230 ranged between Th-232 and Th-228. In all samples investigated, the daughter isotope U-234 showed an excess activity of 19 +/- 7% as compared to the parent isotope U-238. The above nuclides were determined alpha-spectrometrically using Th-229 for thorium, and U-232 for uranium as internal standard.

Animals