USTUR Special Session Roundtable-US Transuranium and Uranium Registries (USTUR): A Five-decade Follow-up of Plutonium and Uranium Workers.

The US Transuranium and Uranium Registries is a human tissue program that collects tissues posthumously from former nuclear workers and radiochemically analyzes them for actinides such as plutonium, americium, and uranium. It was established in 1968 with the goal of advancing science and improving the safety of future workers. Roundtable participants recalled various aspects of this multidisciplinary research program, from establishing consistent autopsy protocols to comparing the registries' findings to those of other programs, such as the historical beagle dog studies and the Russian Radiobiological Human Tissue Repository. The importance of meeting ethical and legal requirements, including written consent forms, was emphasized, as was the need to know whether workers were exposed to nonradiological hazards such as beryllium or asbestos. At Rocky Flats, a bioassay program was established to follow workers after they terminated employment. The resulting data continue to help researchers to improve the biokinetic models that are used to estimate intakes and radiation doses. After 50 y, the US Transuranium and Uranium Registries continues to contribute to our understanding of actinides in humans, which is a testament to the vision of its founders, the generosity of its tissue donors, and the many dedicated scientists who have worked together to achieve a common goal.

Depleted Uranium and Human Health.

Depleted uranium (DU) is generally considered an emerging pollutant, first extensively introduced into environment in the early nineties in Iraq, during the military operation called "Desert Storm". DU has been hypothesized to represent a hazardous element both for soldiers exposed as well as for the inhabitants of the polluted areas in the war zones. In this review, the possible consequences on human health of DU released in the environment are critically analyzed. In the first part, the chemical properties of DU and the principal civil and military uses are summarized. A concise analysis of the mechanisms underlying absorption, blood transport, tissue distribution and excretion of DU in the human body is the subject of the second part of this article. The following sections deal with pathological condition putatively associated with overexposure to DU. Developmental and birth defects, the Persian Gulf syndrome, and kidney diseases that have been associated to DU are the arguments treated in the third section. Finally, data regarding DU exposure and cancer insurgence will be critically analyzed, including leukemia/lymphoma, lung cancer, uterine cervix cancer, breast cancer, bladder cancer and testicular cancer. The aim of the authors is to give a contribution to the debate on DU and its effects on human health and disease.

Bioaccumulation of Uranium and Thorium by Lemna minor and Lemna gibba in Pb-Zn-Ag Tailing Water.

This study focused on the ability of Lemna minor and Lemna gibba to remove U and Th in the tailing water of Keban, Turkey. These plants were placed in tailing water and individually fed to the reactors designed for these plants. Water and plant samples were collected daily from the mining area. The plants were ashed at 300°C for 1 day and analyzed by ICP-MS for U and Th. U was accumulated as a function of time by these plants, and performances between 110 % and 483 % for L. gibba, and between 218 % and 1194 % for L. minor, were shown. The highest Th accumulations in L. minor and L. gibba were observed at 300 % and 600 % performances, respectively, on the second day of the experiment. This study indicated that both L. gibba and L. minor demonstrated a high ability to remove U and Th from tailing water polluted by trace elements.

Internal exposure to uranium in a pooled cohort of gaseous diffusion plant workers.

Intakes and absorbed organ doses were estimated for 29 303 workers employed at three former US gaseous diffusion plants as part of a study of cause-specific mortality and cancer incidence in uranium enrichment workers. Uranium urinalysis data (>600 000 urine samples) were available for 58 % of the pooled cohort. Facility records provided uranium gravimetric and radioactivity concentration data and allowed estimation of enrichment levels of uranium to which workers may have been exposed. Urine data were generally recorded with facility department numbers, which were also available in study subjects' work histories. Bioassay data were imputed for study subjects with no recorded sample results (33 % of pooled cohort) by assigning department average urine uranium concentration. Gravimetric data were converted to 24-h uranium activity excretion using department average specific activities. Intakes and organ doses were calculated assuming chronic exposure by inhalation to a 5-µm activity median aerodynamic diameter aerosol of soluble uranium. Median intakes varied between 0.31 and 0.74 Bq d(-1) for the three facilities. Median organ doses for the three facilities varied between 0.019 and 0.051, 0.68 and 1.8, 0.078 and 0.22, 0.28 and 0.74, and 0.094 and 0.25 mGy for lung, bone surface, red bone marrow, kidneys, and liver, respectively. Estimated intakes and organ doses for study subjects with imputed bioassay data were similar in magnitude.

Low-concentration uranium enters the HepG2 cell nucleus rapidly and induces cell stress response.

This study aimed to compare the cell stress effects of low and high uranium concentrations and relate them to its localization, precipitate formation, and exposure time. The time-course analysis shows that uranium appears in cell nuclei as a soluble form within 5 min of exposure, and quickly induces expression of antioxidant and DNA repair genes. On the other hand, precipitate formations began at the very beginning of exposure at the 300-µM concentration, but took longer to appear at lower concentrations. Adaptive response might occur at low concentrations but are overwhelmed at high concentrations, especially when uranium precipitates are abundant.

Non-destructive determination of uranium, thorium and 40K in tobacco and their implication on radiation dose levels to the human body.

The naturally occurring radionuclides of (235)U, (238)U and (232)Th and their daughter products are a potential major source of anthropogenic radiation to tobacco smokers. Often overlooked is the presence of (40)K in tobacco and its implication to radiation dose accumulation in the human body. In this study, these three radiation sources have been determined in four typical US cigarettes using neutron activation analysis (NAA). The NAA reactions of (238)U(n,γ)(239)U, (232)Th(n,γ)(233)Th and (41)K(n,γ)(42)K were used to determine (235)U, (238)U and (232)Th and (40)K, respectively. The activity of (238)U can easily be determined by epithermal NAA of the (238)U(n,γ)(239)U reaction, and the activity of (235, 234)U can easily be deduced. Using isotopic ratios, the activity due to (40)K was found by the determined concentrations of (41)K (also by epithermal neutrons) in the bulk material. Each gram of total potassium yields 30 Bq of (40)K. The annual effective dose for smokers using 20 cigarettes per day was calculate to be 14.6, 137 and 9 µSv y(-1) for (238,235,) (234)U, (232)Th and (40)K, respectively. These values are significantly lower that the dose received from (210)Po except for (232)Th.

Cellular localization of uranium in the renal proximal tubules during acute renal uranium toxicity.

Renal toxicity is a hallmark of uranium exposure, with uranium accumulating specifically in the S3 segment of the proximal tubules causing tubular damage. As the distribution, concentration and dynamics of accumulated uranium at the cellular level is not well understood, here, we report on high-resolution quantitative in situ measurements by high-energy synchrotron radiation X-ray fluorescence analysis in renal sections from a rat model of uranium-induced acute renal toxicity. One day after subcutaneous administration of uranium acetate to male Wistar rats at a dose of 0.5 mg uranium kg(-1) body weight, uranium concentration in the S3 segment of the proximal tubules was 64.9 ± 18.2 µg g(-1) , sevenfold higher than the mean renal uranium concentration (9.7 ± 2.4 µg g(-1) ). Uranium distributed into the epithelium of the S3 segment of the proximal tubules and highly concentrated uranium (50-fold above mean renal concentration) in micro-regions was found near the nuclei. These uranium levels were maintained up to 8 days post-administration, despite more rapid reductions in mean renal concentration. Two weeks after uranium administration, damaged areas were filled with regenerating tubules and morphological signs of tissue recovery, but areas of high uranium concentration (100-fold above mean renal concentration) were still found in the epithelium of regenerating tubules. These data indicate that site-specific accumulation of uranium in micro-regions of the S3 segment of the proximal tubules and retention of uranium in concentrated areas during recovery are characteristics of uranium behavior in the kidney.

Hyperpolarized [U-(2) H, U-(13) C]Glucose reports on glycolytic and pentose phosphate pathway activity in EL4 tumors and glycolytic activity in yeast cells.

PURPOSE: A resonance at ∼181 ppm in the (13) C spectra of tumors injected with hyperpolarized [U-(2) H, U-(13) C]glucose was assigned to 6-phosphogluconate (6PG), as in previous studies in yeast, whereas in breast cancer cells in vitro this resonance was assigned to 3-phosphoglycerate (3PG). These peak assignments were investigated here using measurements of 6PG and 3PG (13) C-labeling using liquid chromatography tandem mass spectrometry (LC-MS/MS) METHODS: Tumor-bearing mice were injected with (13) C6 glucose and the (13) C-labeled and total 6PG and 3PG concentrations measured. (13) C MR spectra of glucose-6-phosphate dehydrogenase deficient (zwf1Δ) and wild-type yeast were acquired following addition of hyperpolarized [U-(2) H, U-(13) C]glucose and again (13) C-labeled and total 6PG and 3PG were measured by LC-MS/MS RESULTS: Tumor (13) C-6PG was more abundant than (13) C-2PG/3PG and the resonance at ∼181 ppm matched more closely that of 6PG. (13) C MR spectra of wild-type and zwf1Δ yeast cells showed a resonance at ∼181 ppm after labeling with hyperpolarized [U-(2) H, U-(13) C]glucose, however, there was no 6PG in zwf1Δ cells. In the wild-type cells 3PG was approximately four-fold more abundant than 6PG CONCLUSION: The resonance at ∼181 ppm in (13) C MR spectra following injection of hyperpolarized [U-(2) H, U-(13) C]glucose originates predominantly from 6PG in EL4 tumors and 3PG in yeast cells.

Collective dosimetry to distinguish occupational exposure to natural uranium from alimentary uranium background in bioassay measurements.

PURPOSE: To assess occupational exposure from uranium bioassay results which are low and impacted by dietary intakes. MATERIAL AND METHODS: First, the bioassay results of a group of workers exposed to UO2 were compiled along with results of a control group. A Bayesian approach was developed to account for dietary intakes in the calculation of the committed effective dose from occupational exposure of a group of workers. RESULTS: Significant differences in uranium bioassay between the exposed and control groups were found establishing an occupational contamination of the exposed group of workers. Because uranium alimentary excretion estimated from the control group is very variable leading to unreliable individual dose assessment, a collective dosimetric approach was chosen. Applying the Bayesian method, all annual committed effective doses for the exposed group were estimated to be below 0.5 mSv with 95% confidence. CONCLUSIONS: The Bayesian method presented here is well designed to derive best estimate and dose distribution for a group of workers when a contamination is difficult to discriminate from a natural background or alimentary excretion.

Ingestion dose from 238U, 232Th, 226Ra, 40K and 137Cs in cereals, pulses and drinking water to adult population in a high background radiation area, Odisha, India.

A natural high background radiation area is located in Chhatrapur, Odisha in the eastern part of India. The inhabitants of this area are exposed to external radiation levels higher than the global average background values, due to the presence of uranium, thorium and its decay products in the monazite sands bearing placer deposits in its beaches. The concentrations of (232)Th, (238)U, (226)Ra, (40)K and (137)Cs were determined in cereals (rice and wheat), pulses and drinking water consumed by the population residing around this region and the corresponding annual ingestion dose was calculated. The annual ingestion doses from cereals, pulses and drinking water varied in the range of 109.4-936.8, 10.2-307.5 and 0.5-2.8 µSv y(-1), respectively. The estimated total annual average effective dose due to the ingestion of these radionuclides in cereals, pulses and drinking water was 530 µSv y(-1). The ingestion dose from cereals was the highest mainly due to a high consumption rate. The highest contribution of dose was found to be from (226)Ra for cereals and drinking water and (40)K was the major dose contributor from the intake of pulses. The contribution of man-made radionuclide (137)Cs to the total dose was found to be minimum. (226)Ra was found to be the largest contributor to ingestion dose from all sources.

Dosimetric calculations for uranium miners for epidemiological studies.

Epidemiological studies on uranium miners are being carried out to quantify the risk of cancer based on organ dose calculations. Mathematical models have been applied to calculate the annual absorbed doses to regions of the lung, red bone marrow, liver, kidney and stomach for each individual miner arising from exposure to radon gas, radon progeny and long-lived radionuclides (LLR) present in the uranium ore dust and to external gamma radiation. The methodology and dosimetric models used to calculate these organ doses are described and the resulting doses for unit exposure to each source (radon gas, radon progeny and LLR) are presented. The results of dosimetric calculations for a typical German miner are also given. For this miner, the absorbed dose to the central regions of the lung is dominated by the dose arising from exposure to radon progeny, whereas the absorbed dose to the red bone marrow is dominated by the external gamma dose. The uncertainties in the absorbed dose to regions of the lung arising from unit exposure to radon progeny are also discussed. These dose estimates are being used in epidemiological studies of cancer in uranium miners.

Ex vivo decrease in uranium diffusion through intact and excoriated pig ear skin by a calixarene nanoemulsion.

Cutaneous contamination by radionuclides is a major concern in the nuclear industry. In case of skin exposure to uranium, no efficient emergency treatment is available to remove the actinide from the skin. For this purpose, we developed a nanoemulsion containing calixarene molecules displaying good chelating properties towards uranium. In this paper, we describe the ability of this formulation to trap uranium and limit its transfer from the cutaneous contaminated site into the blood. Uranium percutaneous diffusion kinetics was assessed with Franz cells over 24 h through intact and excoriated pig ear skin biopsies, after or without application of the nanoemulsion. Uranium distribution in the skin layers was analysed by SIMS microscopy. The results showed that prompt application of the calixarene nanoemulsion allows a 94% and 98% reduction of the amount of uranium diffused respectively through intact and excoriated skin. The formulation is still efficient in case of delayed application up to 30 minutes since the 24 h-uranium transfer through excoriated skin is reduced by 71%. Besides, no accumulation of uranium or uranium-calixarene chelate was observed in the different skin layers. In conclusion, this study demonstrated the efficiency of the calixarene nanoemulsion, which can be regarded as a promising treatment for uranium cutaneous contamination.

Human risk assessment of heavy metals: principles and applications.

Humans are exposed to a number of "heavy metals" such as cadmium, mercury and its organic form methylmercury, uranium, lead, and other metals as wel as metalloids, such as arsenic, in the environment, workplace, food, and water supply. Exposure to these metals may result in adverse health effects, and national and international health agencies have methodologies to set health-based guidance values with the aim to protect the human population. This chapter introduces the general principles of chemical risk assessment, the common four steps of chemical risk assessment: hazard identification, hazard characterization, exposure assessment, risk characterization, and toxicokinetic and toxicity aspects. Finally, the risk assessments performed by international health agencies such as the World Health Organisation, the Environmental Protection Agency of the United States, and the European Food Safety Authority are reviewed for cadmium, lead, mercury, uranium, and arsenic.

Reprocessed uranium exposure and lung cancer risk.

This study investigated the risk of lung cancer in regards to protracted occupational exposure to reprocessed uranium compounds. Two thousand seven hundred and nine male workers employed at the AREVA NC uranium processing plant between 1960 and 2005 in France were included in the cohort. Historical exposure to reprocessed uranium compounds classified by their solubility type was assessed on the basis of the plant's specific job-exposure matrix. Cox proportional hazard models adjusted for attained age, calendar period, and socioeconomic status were used to estimate relative risks in regards of each type of uranium compound. The relative risk of lung cancer tended to increase with decreasing solubility of reprocessed uranium compounds. The highest-though not statistically significant-relative risk was observed among workers exposed to slowly soluble reprocessed uranium dioxide. This study is the first suggesting an increasing risk of lung cancer associated with exposure to reprocessed uranium. Our results are consistent with data from experimental studies of biokinetics and the action mechanism of slowly soluble uranium compounds, but need to be confirmed in larger studies with more detailed dose-response analyses.

A new formulation containing calixarene molecules as an emergency treatment of uranium skin contamination.

Cutaneous contamination represents the second highest contamination pathway in the nuclear industry. Despite that the entry of actinides such as uranium into the body through intact or wounded skin can induce a high internal exposure, no specific emergency treatment for cutaneous contamination exists. In the present work, an innovative formulation dedicated to uranium skin decontamination was developed. The galenic form consists in an oil-in-water nanoemulsion, which contains a tricarboxylic calixarene known for its high uranium affinity and selectivity. The physicochemical characterization of this topical form revealed that calixarene molecules are located at the surface of the dispersed oil droplets of the nanoemulsion, being thus potentially available for uranium chelation. It was demonstrated in preliminary in vitro experiments by using an adapted ultrafiltration method that the calixarene nanoemulsion was able to extract and retain more than 80% of uranium from an aqueous uranyl nitrate contamination solution. First ex vivo experiments carried out in Franz diffusion cells on pig ear skin explants during 24 h showed that the immediate application of the calixarene nanoemulsion on a skin contaminated by a uranyl nitrate solution allowed a uranium transcutaneous diffusion decrease of about 98% through intact and excoriated skins. The calixarene nanoemulsion developed in this study thus seems to be an efficient emergency system for uranium skin decontamination.

Investigation of uranium accumulation potential and biochemical responses of an aquatic weed Hydrilla verticillata (L.f.) Royle.

The uranium (U) accumulation potential and ensuing biochemical responses were studied in Hydrilla verticillata (L.f.) Royle upon exposure to U (0, 20 and 100 mg L(-1)). There was a concentration-duration dependent increase in U accumulation with the maximum being 78 mg g(-1) DW at 100 mg L(-1) U after 24 h. Plants experienced an initial phase of the maximum toxicity (within 30 min) followed by almost complete recovery after 24 h. The recovery was attributed to an integrated modulation in the level of both enzymatic and molecular antioxidants (viz., guaiacol peroxidase, ascorbate peroxidase, catalase, proline, total phenolics) and also the constituents of thiol metabolism (viz., cysteine and glutathione). Thus, plants were found to be able to accumulate significant amount of U in a short time and to tolerate it efficiently. Hence, they may find application in U phytoremediation considering there accumulation ability, fast growth due to weed-like habit and world-wide distribution.

[Uranium: properties and biological effects after internal contamination]. / Uranium: propriétés et effets biologiques après contamination interne.

Uranium is a radionuclide present in the environment since the origin of the Earth. In addition to natural uranium, recent deposits from industrial or military activities are acknowledged. Uranium's toxicity is due to a combination of its chemical (heavy metal) and radiological properties (emission of ionizing radiations). Acute toxicity induces an important weight loss and signs of renal and cerebral impairment. Alterations of bone growth, modifications of the reproductive system and carcinogenic effects are also often seen. On the contrary, the biological effects of a chronic exposure to low doses are unwell known. However, results from different recent studies suggest that a chronic contamination with low levels of uranium induces subtle but significant levels. Indeed, an internal contamination of rats for several weeks leads to detection of uranium in many cerebral structures, in association with an alteration of short-term memory and an increase of anxiety level. Biological effects of uranium on the metabolisms of xenobiotics, steroid hormones and vitamin D were described in the liver, testis and kidneys. These recent scientific data suggest that uranium could participate to increase of health risks linked to environmental pollution.

Inhalation and ingestion intakes with associated dose estimates for level II and level III personnel using Capstone study data.

Depleted uranium (DU) intake rates and subsequent dose rates were estimated for personnel entering armored combat vehicles perforated with DU penetrators (level II and level III personnel) using data generated during the Capstone DU Aerosol Study. Inhalation intake rates and associated dose rates were estimated from cascade impactors worn by sample recovery personnel and from cascade impactors that served as area monitors. Ingestion intake rates and associated dose rates were estimated from cotton gloves worn by sample recovery personnel and from wipe-tests samples from the interior of vehicles perforated with large-caliber DU munitions. The mean DU inhalation intake rate for level II personnel ranged from 0.447 mg h(-1) based on breathing zone monitor data (in and around a perforated vehicle) to 14.5 mg h(-1) based on area monitor data (in a perforated vehicle). The mean DU ingestion intake rate for level II ranged from 4.8 mg h(-1) to 38.9 mg h(-1) based on the wipe-tests data including surface-to-glove transfer factors derived from the Capstone data. Based on glove contamination data, the mean DU ingestion intake rates for level II and level III personnel were 10.6 mg h(-1) and 1.78 mg h(-1), respectively. Effective dose rates and peak kidney uranium concentration rates were calculated based on the intake rates. The peak kidney uranium concentration rate cannot be multiplied by the total exposure duration when multiple intakes occur because uranium will clear from the kidney between the exposures.

Inositol hexaphosphate: a potential chelating agent for uranium.

Chelation therapy is an optimal method to reduce the radionuclide-related risks. In the case of uranium incorporation, the treatment of choice is so far i.v infusion of a 1.4% sodium bicarbonate solution, but the efficacy has been proved to be not very high. In this study, we examine the efficacy of some substances: bicarbonate, citrate, diethylenetriamine pentaacetic acid (DTPA), ethidronate (EHBP) and inositol hexaphosphate (phytic acid) to chelate uranium using a test developed by Braun et al. Different concentrations of phytic acid, an abundant component of plant seeds that is widely distributed in animal cells and tissues in substantial levels, were tested and compared to the same concentrations of sodium citrate, bicarbonate, EHBP and DTPA. The results showed a strong affinity of inositol hexaphosphate for uranium, suggesting that it could be an effective chelating agent for uranium in vivo.

Percutaneous penetration of uranium in rats after a contamination on intact or wounded skin.

The aim of this work is to assess in vivo in a hairless rat model, the percutaneous diffusion of uranium through intact or wounded rat skin. Six types of wounds were simulated by excoriation and burns with 10 N HF, 2, 5 and 14 N HNO3 and 10 N NaOH on anaesthetised hairless rats. Percutaneous penetration through wounded skin towards blood and subsequent urinary excretion of uranium was followed in vivo during 24 h. The influence of the physicochemical form (solution or powder) of uranyl nitrate (UN) on its percutaneous diffusion was also investigated. UN, even as a powder, can diffuse through intact skin. The presence of uranium in blood is more persistent and its urinary elimination is slower after an HF burn than after an HNO3 burn. Excoriation increases dramatically percutaneous absorption of UN. Thus, percutaneous diffusion of UN is largely dependent on skin barrier integrity with a particular importance of stratum corneum.