Renal toxicity and biokinetics models after repeated uranium instillation.

During nuclear fuel processing, workers can potentially be exposed to repeated inhalations of uranium compounds. Uranium nephrotoxicity is well documented after acute uranium intake, but it is controversial after long-term or protracted exposure. This study aims to analyze the nephrotoxicity threshold after repeated uranium exposure through upper airways and to investigate the resulting uranium biokinetics in comparison to reference models. Mice (C57BL/6J) were exposed to uranyl nitrate (0.03-3 mg/kg/day) via intranasal instillation four times a week for two weeks. Concentrations of uranium in urines and tissues were measured at regular time points (from day 1 to 91 post-exposure). At each exposure level, the amount of uranium retained in organs/tissues (kidney, lung, bone, nasal compartment, carcass) and excreta (urine, feces) reflected the two consecutive weeks of instillation except for renal uranium retention for the highest uranium dose. Nephrotoxicity biomarkers, KIM-1, clusterin and osteopontin, are induced from day 4 to day 21 and associated with changes in renal function (arterial fluxes) measured using non-invasive functional imaging (Doppler-ultrasonography) and confirmed by renal histopathological analysis. These results suggest that specific biokinetic models should be developed to consider altered uranium excretion and retention in kidney due to nephrotoxicity. The threshold is between 0.25 and 1 mg/kg/day after repeated exposure to uranium via upper airways.

Analysis of the association between ionizing radiation and mortality in uranium workers from five plants involved in the nuclear fuel production cycle in France.

PURPOSE: The aim is to investigate associations between mortality and exposure to ionizing radiation in a cohort of uranium workers with potential for internal and external radiation exposures. METHODS: Workers employed for at least 6 months between 1958 and 2006 in five plants involved in the French nuclear fuel cycle were included and followed up between 1968 and 2013. Cause-specific standardized mortality ratios were calculated. Analyses of associations between individual cumulative radiation dose (both internal and external, lagged by 5-15 years) and mortality were conducted using Poisson regression. RESULTS: The cohort includes 4541 workers. The mean cumulative external dose was 11.12 mGy. Mean cumulative internal doses ranged, depending on modelling hypotheses, from 0.05 to 0.09 mGy (liver) and from 4.22 to 10.90 mGy (lung). At the end of the follow-up, 838 workers were deceased and 28 lost to follow-up. A healthy worker effect was observed. The risk of prostate and lung cancers mortality was significantly higher for workers exposed to cumulative external dose above 50 mGy compared to non-exposed, but these associations were based only on three cases and became non-significant, although of similar magnitude, after adjustment for smoking. Associations with internal dose showed no consistent pattern. CONCLUSIONS: For the first time, a study was conducted in a French cohort of uranium workers with a complete reconstruction of internal dose. Results are preliminary and must be interpreted with caution because of the limited cohort size and significant sources of uncertainty. Future steps of this study will overcome these limitations.

INITIAL EVALUATION OF INDIVIDUAL DOSES IN THE EARLY PHASE OF A NUCLEAR REACTOR ACCIDENT BASED ON IN-VIVO MONITORING DATA AND SIMULATED RADIOLOGICAL CONSEQUENCES.

In the early phase of a nuclear reactor accident, in-vivo monitoring of impacted population would be highly useful to detect potential contamination during the passage of the cloud and to estimate the dose from inhalation of measured radionuclides. However, it would be important to take into account other exposure components: (1) inhalation of unmeasured radionuclides and (2) external irradiation from the plume and from the radionuclides deposited on the soil. This article presents a methodology to calculate coefficients used to convert in-vivo measurement results directly into doses, not only from the measured radionuclides but from all sources of exposure according to model-based projected doses. This early interpretation of in-vivo measurements will provide an initial indication of individual exposure levels. As an illustration, the methodology is applied to two scenarios of accidents affecting a nuclear power plant: a loss-of-coolant accident leading to core meltdown and a steam generator tube rupture accident.

Circulatory disease in French nuclear fuel cycle workers chronically exposed to uranium: a nested case-control study.

OBJECTIVES: There is growing evidence of an association between low-dose external γ-radiation and circulatory system diseases (CSDs), yet sparse data exist about an association with chronic internal uranium exposure and the role of non-radiation risk factors. We conducted a nested case-control study of French AREVA NC Pierrelatte nuclear workers employed between 1960 and 2005 to estimate CSD risks adjusting for major CSD risk factors (smoking, blood pressure, body mass index, total cholesterol and glycaemia) and external γ-radiation dose. METHODS: The study included 102 cases of death from CSD and 416 controls individually matched on age, gender, birth cohort and socio-professional status. Information on CSD risk factors was collected from occupational medical records. Organ-specific absorbed doses were estimated using biomonitoring data, taking into account exposure regime and uranium physicochemical properties. External γ-radiation was measured by individual dosimeter badges. Analysis was conducted with conditional logistic regression. RESULTS: Workers were exposed to very low radiation doses (mean γ-radiation dose 2 and lung uranium dose 1 mGy). A positive but imprecise association was observed (excess OR per mGy 0.2, 95% CI 0.004 to 0.5). Results obtained after adjustment suggest that uranium exposure might be an independent CSD risk factor. CONCLUSIONS: Our results suggest that a positive association might exist between internal uranium exposure and CSD mortality, not confounded by CSD risk factors. Future work should focus on numerous uncertainties associated with internal uranium dose estimation and on understanding biological pathway of CSD after protracted low-dose internal radiation exposure.

Optimization of Routine Monitoring of Workers Exposed to Plutonium Aerosols.

In case of incidental confinement failure, mixed oxide (MOX) fuel preparation may expose workers to plutonium aerosols. Due to its potential toxicity, occupational exposure to plutonium compounds should be kept as low as reasonably achievable. To ensure the absence of significant intake of radionuclides, workers at risk of internal contamination are monitored by periodic bioassay planned in a routine monitoring programme. From bioassay results, internal dose may be estimated. However, accurate dose calculation relies on known exposure conditions, which are rarely available when the exposure is demonstrated by routine monitoring only. Therefore, internal dose calculation is subject to uncertainty from unknown exposure conditions and from activity measurement variability. The present study calculates the minimum detectable dose (MDD) for a routine monitoring programme by considering all plausible conditions of exposure and measurement uncertainty. The MDD evaluates the monitoring quality and can be used for optimization. Here, MDDs were calculated for the monitoring of workers preparing MOX fuel. Uncertain parameters were modelled by probability distributions defined according to information provided by experts of routine monitoring, of workplace radiological protection and of bioassay analysis. Results show that the current monitoring is well adapted to potential exposure. A sensitivity study of MDD highlights high dependence on exposure condition modelling. Integrating all expert knowledge is therefore crucial to obtain reliable MDD estimates, stressing the value of a holistic approach to worker monitoring.

Concerted Uranium Research in Europe (CURE): toward a collaborative project integrating dosimetry, epidemiology and radiobiology to study the effects of occupational uranium exposure.

The potential health impacts of chronic exposures to uranium, as they occur in occupational settings, are not well characterized. Most epidemiological studies have been limited by small sample sizes, and a lack of harmonization of methods used to quantify radiation doses resulting from uranium exposure. Experimental studies have shown that uranium has biological effects, but their implications for human health are not clear. New studies that would combine the strengths of large, well-designed epidemiological datasets with those of state-of-the-art biological methods would help improve the characterization of the biological and health effects of occupational uranium exposure. The aim of the European Commission concerted action CURE (Concerted Uranium Research in Europe) was to develop protocols for such a future collaborative research project, in which dosimetry, epidemiology and biology would be integrated to better characterize the effects of occupational uranium exposure. These protocols were developed from existing European cohorts of workers exposed to uranium together with expertise in epidemiology, biology and dosimetry of CURE partner institutions. The preparatory work of CURE should allow a large scale collaborative project to be launched, in order to better characterize the effects of uranium exposure and more generally of alpha particles and low doses of ionizing radiation.

Influence of DTPA Treatment on Internal Dose Estimates.

In case of internal contamination with plutonium materials, a treatment with diethylene triamine pentaacetic acid (DTPA) can be administered in order to reduce plutonium body burden and consequently avoid some radiation dose. DTPA intravenous injections or inhalation can start almost immediately after intake, in parallel with urinary and fecal bioassay sampling for dosimetric follow-up. However, urine and feces excretion will be significantly enhanced by the DTPA treatment. As internal dose is calculated from bioassay results, the DTPA effect on excretion has to be taken into account. A common method to correct bioassay data is to divide it by a factor representing the excretion enhancement under DTPA treatment by intravenous injection. Its value may be based on a nominal reference or observed after a break in the treatment. The aim of this study was to estimate the influence of this factor on internal dose by comparing the dose estimated using default or upper and lower values of the enhancement factor for 11 contamination cases. The observed upper and lower values of the enhancement factor were 18.7 and 63.0 for plutonium and 24.9 and 28.8 for americium. For americium, a default factor of 25 is proposed. This work demonstrates that the use of a default DTPA enhancement factor allows the determination of the magnitude of the contamination because dose estimated could vary by a factor of 2 depending on the value of the individual DTPA enhancement factor. In case of significant intake, an individual enhancement factor should be determined to obtain a more reliable dose assessment.

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.

Physico-chemical characteristics of uranium compounds: a review.

PURPOSE: To collect values of parameters describing the physico-chemical properties of different uranium compounds in order to quantify their variability and to propose specific parameters for different workplaces and compounds. MATERIAL AND METHODS: The published values of absorption parameters, gastrointestinal absorption fractions, activity median aerodynamic diameters and geometric standard deviations of the particle size activity distribution were collected. RESULTS: Average and median values for each chemical form and workplace were determined for these parameters. These values can be used when no precise information is known for dose assessment following internal contamination by uranium. This review presents and discusses the variability of these parameters for the different uranium chemical forms and workplaces. Finally, sensitivity of the dose coefficients to these parameters was quantified. CONCLUSION: Specific parameter values for different workplaces and compounds were proposed and the variability quantified.

Absorption of americium compounds in the respiratory tract.

PURPOSE: To improve the dosimetry of incorporated americium (Am) and to contribute to radiation protection by characterizing the absorption kinetics of inhaled Am compounds. MATERIAL AND METHODS: In vitro dissolution tests, animal experiments and human contamination cases published in the literature were reviewed. The data were analyzed with biokinetic models consistent with the current publications of the International Commission on Radiological Protection. RESULTS: Material-specific dissolution parameter values with consequent assignment to absorption Types are proposed as well as representative central values for the different chemical forms of Am. CONCLUSIONS: The absorption of Am oxide is consistent with the moderate absorption Type M while Am nitrate appears more soluble. Am associated with plutonium oxide usually follows its slow absorption Type S. However, the large variability observed stresses the value of investigating the specific absorption kinetics for Am compounds which represent a significant risk of internal exposure.