Sergei Y. Tolmachev

Elemental bio-imaging of thorium, uranium and plutonium in tissues from occupationally exposed former nuclear workers

Internal exposure from naturally occurring radionuclides (including the inhaled long-lived actinides (232)Th and (238)U) is a component of the ubiquitous background radiation dose (National Council on Radiation Protection and Measurements. Ionizing radiation exposure of the population of the United States; NCRP Report No. 160; NCRP: Bethesda, MD, 2009). It is of interest to compare the concentration distribution of these natural alpha-emitters in the lungs and respiratory lymph nodes with those resulting from occupational exposure, including exposure to anthropogenic plutonium and depleted and enriched uranium. This study examines the application of laser ablation-inductively coupled plasma-mass spectrometry (LA-ICPMS) to quantifying and visualizing the mass distribution of uranium and thorium isotopes from both occupational and natural background exposure in human respiratory tissues and, for the first time, extends this application to the direct imaging of plutonium isotopes. Sections of lymphatic and lung tissues taken from deceased former nuclear workers with a known history of occupational exposure to specific actinide elements (uranium, plutonium, or americium) were analyzed by LA-ICPMS. Using a previously developed LA-ICPMS protocol for elemental bio-imaging of trace elements in human tissue and a new software tool, we generated images of thorium ((232)Th), uranium ((235)U and (238)U), and plutonium ((239)Pu and (240)Pu) mass distributions in sections of tissue. We used a laboratory-produced matrix-matched standard to quantify the (232)Th, (235)U, and (238)U concentrations. The plutonium isotopes (239)Pu and (240)Pu were detected by LA-ICPMS in 65 mum diameter localized regions of both a paratracheal lymph node and a sample of lung tissue from a person who was occupationally exposed to refractory plutonium (plutonium dioxide). The average (overall) (239)Pu concentration in the lymph node was 39.2 ng/g, measured by high purity germanium (HPGe) gamma-spectrometry (Lynch, T. P.; Tolmachev, S. Y.; James, A. C. Radiat. Prot. Dosim. 2009, 134, 94-101). Localized mass concentrations of thorium ((232)Th) and uranium ((238)U) in lymph node tissue from a person not occupationally exposed to these elements (chronic natural background inhalation exposure) ranged up to 400 and 375 ng/g, respectively. In lung samples of occupationally nonexposed to thorium and uranium workers, (232)Th and (238)U concentrations ranged up to 200 and 170 ng/g, respectively. In a person occupationally exposed to air-oxidized uranium metal (Adley, F. E.; Gill, W. E.; Scott, R. H. Study of atmospheric contaminiation in the melt plant buiding. HW-23352(Rev.); United States Atomic Energy Commission: Oakridge, TN, 1952, p 1-97), the maximum (235)U and (238)U isotopic mass concentrations in a lymph node, measured at higher resolution (with a 30 mum laser spot diameter), were 70 and 8500 ng/g, respectively. The ratio of these simultaneously measured mass concentrations signifies natural uranium. The current technique was not sufficiently sensitive, even with a 65 mum laser spot diameter, to detect (241)Am (at an overall tissue concentration of 0.024 ng/g, i.e., 3 Bq/g).

Uranium bone content as an indicator of chronic environmental exposure from drinking water

Uranium (U) is an ubiquitous radioelement found in drinking water and food. As a consequence of its prevalence, most humans ingest a few micrograms (μg) of this element daily. It is incorporated in various organs and tissues. Several studies have demonstrated that ingested U is deposited mainly in bones. Therefore, U skeletal content could be considered as a prime indicator for low-level chronic intake. In this study, 71 archived vertebrae bone samples collected in seven Canadian cities were subjected to digestion and U analysis by inductively coupled plasma mass spectrometry. These results were correlated with U concentrations in municipal drinking water supplies, with the data originating from historical studies performed by Health Canada. A strong relationship (r(2) = 0.97) was observed between the averaged U total skeletal content and averaged drinking water concentration, supporting the hypothesis that bones are indeed a good indicator of U intake. Using a PowerBASIC compiler to process an ICRP systemic model for U (ICRP, 1995a), U total skeletal content was estimated using two gastrointestinal tract absorption factors (ƒ1 = 0.009 and 0.03). Comparisons between observed and modelled skeletal contents as a function of U intake from drinking water tend to demonstrate that neither of the ƒ1 values can adequately estimate observed values. An ƒ1value of 0.009 provides a realistic estimate for intake resulting from food consumption only (6.72 μg) compared to experimental data (7.4 ± 0.8 μg), whereas an ƒ1value of 0.03 tends to better estimate U skeletal content at higher levels of U (1-10 μg L(-1)) in drinking water.

Analyses of Radiation and Mesothelioma in the US Transuranium and Uranium Registries

OBJECTIVES We examined the relationship between radiation and excess deaths from mesothelioma among deceased nuclear workers who were part of the US Transuranium and Uranium Registries. METHODS We performed univariate analysis with SAS Version 9.1 software. We conducted proportionate mortality ratio (PMR) and proportionate cancer mortality ratio (PCMR) analyses using the National Institute for Occupational Safety and Health Life Table Analysis System with the referent group being all deaths in the United States. RESULTS We found a PMR of 62.40 (P < .05) and a PCMR of 46.92 (P < .05) for mesothelioma. PMRs for the 4 cumulative external radiation dose quartiles were 61.83, 57.43, 74.46, and 83.31. PCMRs were 36.16, 47.07, 51.35, and 67.73. The PMR and PCMR for trachea, bronchus, and lung cancer were not significantly elevated. CONCLUSIONS The relationship between cumulative external radiation dose and the PMR and PCMR for mesothelioma suggests that external radiation at nuclear facilities is associated with an increased risk of mesothelioma. The lack of a significantly elevated PMR and PCMR for trachea, bronchus, and lung cancer suggests that asbestos did not confound this relationship.

Concentration and daily excretion of uranium in urine of Japanese.

A study was undertaken to investigate uranium concentrations in urine samples for unexposed Japanese individuals and to evaluate uranium daily excretion. Uranium concentrations were measured with inductively coupled plasma mass spectrometry after microwave-assisted digestion and online separation using the UTEVA extraction chromatographic resin. The concentrations ranged from 0.8 to 35.6 ng of uranium per liter of urine (median 4.5 ng L−1). Urinary uranium was normalized relative to the creatinine concentration in order to compensate for the degree of urine dilution. Creatinine-normalized values ranged from 1.2 to 17.8 ng of uranium per gram of creatinine (median 7.4 ng g−1 creatinine). These results corresponded to the lower end of urinary uranium reported for unexposed populations. The level of daily excreted uranium was calculated as 6.45 ng d−1 (median value) using ICRP recommended values for 24-h creatinine excretion. These data along with literature data on uranium dietary intake for Japanese populations were used to estimate the uranium gastrointestinal absorption fraction (f1). The median f1 value was calculated to be 0.007. Statistical analysis was done to investigate statistical differences and relationships between the studied variables.

Microdistribution and Long-term Retention of 239Pu (NO3)4 in the Respiratory Tracts of an Acutely Exposed Plutonium Worker and Experimental Beagle Dogs

The long-term retention of inhaled soluble forms of plutonium raises concerns as to the potential health effects in persons working in nuclear energy or the nuclear weapons program. The distributions of long-term retained inhaled plutonium-nitrate [(239)Pu (NO(3))(4)] deposited in the lungs of an accidentally exposed nuclear worker (Human Case 0269) and in the lungs of experimentally exposed beagle dogs with varying initial lung depositions were determined via autoradiographs of selected histologic lung, lymph node, trachea, and nasal turbinate tissue sections. These studies showed that both the human and dogs had a nonuniform distribution of plutonium throughout the lung tissue. Fibrotic scar tissue effectively encapsulated a portion of the plutonium and prevented its clearance from the body or translocation to other tissues and diminished dose to organ parenchyma. Alpha radiation activity from deposited plutonium in Human Case 0269 was observed primarily along the subpleural regions while no alpha activity was seen in the tracheobronchial lymph nodes of this individual. However, relatively high activity levels in the tracheobronchial lymph nodes of the beagles indicated the lymphatic system was effective in clearing deposited plutonium from the lung tissues. In both the human case and beagle dogs, the appearance of retained plutonium within the respiratory tract was inconsistent with current biokinetic models of clearance for soluble forms of plutonium. Bound plutonium can have a marked effect on the dose to the lungs and subsequent radiation exposure has the potential to increase cancer risk.

Measurement of 236U in human tissue samples using solid phase extraction coupled to ICP-MS

236U is present at ultra-trace levels in typical environmental and biological samples. Typically, it has been measured by highly sensitive techniques, such as accelerator mass spectrometry. This paper reports the measurement of 236U in 20 human tissue samples using a sector field ICP-MS following automated SPE separation. The tissue samples were selected from one USTUR case, representing tissues/organs that are important for internal radiation assessment. Another uranium isotope, 235U, was also measured in the samples. The results for 235U were compared with those obtained by alpha spectrometry. For most cases, results from the two methods were comparable, indicating that the measurement of 236U in the samples is reliable.

Carcinogenic and inflammatory effects of plutonium-nitrate retention in an exposed nuclear worker and beagle dogs.

Abstract Purpose: Plutonium-nitrate has a moderately rapid translocation rate from the lung to blood stream. Previous studies have shown an unexpected retention of soluble plutonium in the beagles and human case studied here. The inflammatory responses that may be associated with long-term exposure to ionizing radiation were characterized. These pathways include tissue injury, apoptosis, and gene expression modifications. Other protein modifications related to carcinogenesis and inflammation and the various factors that may play a role in orchestrating complex interactions which influence tissue integrity following irradiation were investigated. Materials and methods: We have examined numerous lung samples from a plutonium-exposed worker, a human control, and a variety of plutonium-exposed beagle dogs using immunohistochemistry and quantitative Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). Results: The exposed human showed interstitial fibrosis in peripheral regions of the lung, but no pulmonary tumors. Beagles with similar doses were diagnosed with tumors in bronchiolo-alveolar, peripheral and sub-pleural alveolar regions of the lung. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay showed an elevation of apoptosis in tracheal mucosa, tumor cells, and nuclear debris in the alveoli and lymph nodes of the beagles but not in the human case. In both the beagles and human there were statistically significant modifications in the expression of Fas ligand (FASLG), B-cell lymphoma 2 (BCL2), and Caspase 3 (CASP3). Conclusions: The data suggests that FASLG, BCL2, CASP3 and apoptosis play a role in the inflammatory responses following prolonged plutonium exposure. Utilizing these unique tissues revealed which pathways are triggered following the internal deposition and long-term retention of plutonium-nitrate in a human and a large animal model.

THE MAYAK WORKER DOSIMETRY SYSTEM (MWDS 2013): A RE-ANALYSIS OF USTUR CASE 0269 TO DETERMINE WHETHER PLUTONIUM BINDS TO THE LUNGS

Radionuclides in ionic form can become chemically bound in the airways of the lungs following dissolution of inhaled particulates in lung fluid. The presence of long-term binding can greatly increase lung doses from inhaled plutonium, particularly if it occurs in the bronchial and bronchiolar regions. However, the only published evidence that plutonium binding occurs in humans comes from an analysis of the autopsy and bioassay data of United States Transuranium and Uranium Registries Case 0269, a plutonium worker who experienced a very high (58 kBq) acute inhalation of plutonium nitrate. This analysis suggested a bound fraction of around 8 %, inferred from an unexpectedly low ratio of estimated total thoracic lymph node activity:total lung activity, at the time of death. However, there are some limitations with this study, the most significant being that measurements of the regional distribution of plutonium activity in the lungs, which provide more direct evidence of binding, were not available when the analysis was performed. The present work describes the analysis of new data, which includes measurements of plutonium activity in the alveolar-interstitial (AI) region, bronchial (BB) and bronchiolar (bb) regions, and extra-thoracic (ET) regions, at the time of death. A Bayesian approach is used that accounts for uncertainties in model parameter values, including particle transport clearance, which were not considered in the original analysis. The results indicate that a long-term bound fraction between 0.4 and 0.7 % is required to explain this data, largely because plutonium activity is present in the extra-thoracic (ET2), bronchial and bronchiolar airways at the time of death.

Natural Uranium Tissue Content of Three Caucasian Males.

AbstractUranium content and concentrations were measured in the tissues of three Caucasian male whole body donors to the U.S. Transuranium and Uranium Registries with no known intake other than from natural environmental sources. Average total body uranium content in the three cases was 81.3 ± 22.3 &mgr;g, of which 37.2 ± 2.1 &mgr;g (46%) was in the skeleton. The skeleton had a mean concentration of 3.79 ± 0.45 &mgr;g U kg−1 wet weight and 11.72 ± 1.49 &mgr;g U kg−1 ash. Distribution was in bone volume and not predominately on bone surfaces. Soft tissue concentrations ranged over about an order of magnitude, averaging about 0.5 &mgr;g kg−1 wet weight for all tissues except the thoracic lymph nodes, which averaged 32.3 times the mean for soft tissue of the three cases. Observed thyroid tissue concentrations were about an order of magnitude greater than the average soft tissue concentration in two of the three background cases, suggestive of a possible long-term depot in this organ. Kidney content of uranium averaged 0.38 ± 0.21 &mgr;g for the three cases, an order of magnitude lower than the 7 &mgr;g recommended for Reference Man. The lower content and concentration in the kidney do not support a significant long-term depot for uranium in that organ. Assuming equilibrium between intake and excretion, the tissue data suggest a transfer coefficient from blood to skeleton of 0.14 with a residence half-life in the skeleton of 4,950 d (13.56 y), significantly greater than the 1,500 d (4.1 y) half-time proposed by ICRP.

The US Transuranium and Uranium Registries: forty years' experience and new directions in the analysis of actinides in human tissues

Abstract The US Transuranium and Uranium Registries (USTUR) studies the distribution, biokinetics and tissue dosimetry of actinide elements through radiochemical analysis of autopsy tissues voluntarily donated by occupationally exposed persons. The paper provides an overview of the analytical methods for plutonium (Pu), americium (Am) and uranium (U) isotopic determination in human tissues currently applied at USTUR. The results of inter-comparing 239+240Pu, 241Am and 234,235,238U determinations by sector field inductively coupled mass spectrometry (SF-ICP-MS), α-spectrometry (AS) and kinetic phosphorescence analysis (KPA) are discussed. SF-ICP-MS is a major advance over AS and KPA in enabling the measurement of the 240Pu/ 239Pu atom ratio, the short-lived β-emitter 241Pu, and long-lived 236U. For the first time, 241Am and 241Pu were measured in human tissues using SF-ICP-MS. The paper also presents a new avenue of USTUR research in the application of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to elemental bio-imaging (EBI) of the actinides in human tissues.