Assessing the reliability of dose coefficients for exposure to radioiodine by members of the public, accounting for dosimetric and risk model uncertainties.

Assessments of risk to a specific population group resulting from internal exposure to a particular radionuclide can be used to assess the reliability of the appropriate International Commission on Radiological Protection (ICRP) dose coefficients used as a radiation protection device for the specified exposure pathway. An estimate of the uncertainty on the associated risk is important for informing judgments on reliability; a derived uncertainty factor, UF, is an estimate of the 95% probable geometric difference between the best risk estimate and the nominal risk and is a useful tool for making this assessment. This paper describes the application of parameter uncertainty analysis to quantify uncertainties resulting from internal exposures to radioiodine by members of the public, specifically 1, 10 and 20-year old females from the population of England and Wales. Best estimates of thyroid cancer incidence risk (lifetime attributable risk) are calculated for ingestion or inhalation of 129I and 131I, accounting for uncertainties in biokinetic model and cancer risk model parameter values. These estimates are compared with the equivalent ICRP derived nominal age-, sex- and population-averaged estimates of excess thyroid cancer incidence to obtain UFs. Derived UF values for ingestion or inhalation of 131I for 1 year, 10-year and 20-year olds are around 28, 12 and 6, respectively, when compared with ICRP Publication 103 nominal values, and 9, 7 and 14, respectively, when compared with ICRP Publication 60 values. Broadly similar results were obtained for 129I. The uncertainties on risk estimates are largely determined by uncertainties on risk model parameters rather than uncertainties on biokinetic model parameters. An examination of the sensitivity of the results to the risk models and populations used in the calculations show variations in the central estimates of risk of a factor of around 2-3. It is assumed that the direct proportionality of excess thyroid cancer risk and dose observed at low to moderate acute doses and incorporated in the risk models also applies to very small doses received at very low dose rates; the uncertainty in this assumption is considerable, but largely unquantifiable. The UF values illustrate the need for an informed approach to the use of ICRP dose and risk coefficients.

A Bayesian analysis of plutonium exposures in Sellafield workers.

The joint Russian (Mayak Production Association) and British (Sellafield) plutonium worker epidemiological analysis, undertaken as part of the European Union Framework Programme 7 (FP7) SOLO project, aims to investigate potential associations between cancer incidence and occupational exposures to plutonium using estimates of organ/tissue doses. The dose reconstruction protocol derived for the study makes best use of the most recent biokinetic models derived by the International Commission on Radiological Protection (ICRP) including a recent update to the human respiratory tract model (HRTM). This protocol was used to derive the final point estimates of absorbed doses for the study. Although uncertainties on the dose estimates were not included in the final epidemiological analysis, a separate Bayesian analysis has been performed for each of the 11 808 Sellafield plutonium workers included in the study in order to assess: A. The reliability of the point estimates provided to the epidemiologists and B. The magnitude of the uncertainty on dose estimates. This analysis, which accounts for uncertainties in biokinetic model parameters, intakes and measurement uncertainties, is described in the present paper. The results show that there is excellent agreement between the point estimates of dose and posterior mean values of dose. However, it is also evident that there are significant uncertainties associated with these dose estimates: the geometric range of the 97.5%:2.5% posterior values are a factor of 100 for lung dose, 30 for doses to liver and red bone marrow, and 40 for intakes: these uncertainties are not reflected in estimates of risk when point doses are used to assess them. It is also shown that better estimates of certain key HRTM absorption parameters could significantly reduce the uncertainties on lung dose in future studies.

An assessment of the reliability of dose coefficients for intakes of radionuclides by members of the public.

This paper summarises work undertaken on behalf of the Environment Agency for England to quantify uncertainties resulting from internal exposures to a number of radionuclides considered significant because of their anthropogenic origin, namely: (238)U, (226)Ra, (239)Pu, (241)Am, (137)Cs, (90)Sr, (131)I, (129)I and (3)H. Uncertainties in the biokinetic models that are used to calculate the retention and excretion of radionuclides are derived in order to calculate distributions of effective dose per unit intake following their inhalation or ingestion by members of the UK public. The central values and ranges of the distributions are used to inform the derivation of uncertainty factors (UFs) for the different dose coefficients, which can be used to assess reliability. These represent uncertainties inherent in the structures of the biokinetic models and their parameter values. The inferred UF values are typically around 2-3 for ingestion and 2-6 for inhalation for all age groups, and are comparable to UF values inferred from published studies. It is instructive to consider these ranges alongside the likely levels of exposure that are expected from the radionuclides considered (the microsievert range) and the dose limit of planned exposures for members of the public (1000 µSv).

Plutonium worker dosimetry.

Epidemiological studies of the relationship between risk and internal exposure to plutonium are clearly reliant on the dose estimates used. The International Commission on Radiological Protection (ICRP) is currently reviewing the latest scientific information available on biokinetic models and dosimetry, and it is likely that a number of changes to the existing models will be recommended. The effect of certain changes, particularly to the ICRP model of the respiratory tract, has been investigated for inhaled forms of (239)Pu and uncertainties have also been assessed. Notable effects of possible changes to respiratory tract model assumptions are (1) a reduction in the absorbed dose to target cells in the airways, if changes under consideration are made to the slow clearing fraction and (2) a doubling of absorbed dose to the alveolar region for insoluble forms, if evidence of longer retention times is taken into account. An important factor influencing doses for moderately soluble forms of (239)Pu is the extent of binding of dissolved plutonium to lung tissues and assumptions regarding the extent of binding in the airways. Uncertainty analyses have been performed with prior distributions chosen for application in epidemiological studies. The resulting distributions for dose per unit intake were lognormal with geometric standard deviations of 2.3 and 2.6 for nitrates and oxides, respectively. The wide ranges were due largely to consideration of results for a range of experimental data for the solubility of different forms of nitrate and oxides. The medians of these distributions were a factor of three times higher than calculated using current default ICRP parameter values. For nitrates, this was due to the assumption of a bound fraction, and for oxides due mainly to the assumption of slower alveolar clearance. This study highlights areas where more research is needed to reduce biokinetic uncertainties, including more accurate determination of particle transport rates and long-term dissolution for plutonium compounds, a re-evaluation of long-term binding of dissolved plutonium, and further consideration of modeling for plutonium absorbed to blood from the lungs.

MWDS-2016: THE SLOW DISSOLUTION RATE FOR PLUTONIUM NITRATE INTAKES AT THE MAYAK FACILITY.

The slow dissolution rate of material deposited in the lung plays a key role in determining the eventual radiation dose received by the lung. It is therefore of great importance to establish a reliable value for this parameter, to incorporate into the latest Mayak Worker Dosimetry System (MWDS-2016). Disparate values have been obtained for the slow dissolution rate of plutonium nitrate. A volunteer study performed by Public Health England (PHE) and an analysis of United States Transuranium and Uranium Registries (USTUR) case 0269 have yielded slow dissolution rates in the region of 10-40 × 10-4 d-1. However, autopsies performed on 20 Mayak workers, exposed predominantly to nitrates, have resulted in estimates of slow dissolution rates of around 2.4 × 10-4 d-1. Three hypotheses have been proposed to explain this discrepancy: (1) a slower dissolution rate in the interstitium, (2) a third exponential component in the dissolution function and (3) a small component of oxide in the aerosol to which Mayak 'nitrate' workers were exposed. This paper describes tests of these competing hypotheses. Bayesian methods have been applied to the following datasets: PHE volunteer data; Beagle dog data; USTUR cases and Mayak worker data. It is concluded that a mixture of oxide and nitrate material, with the oxide forming ~14% of the intake, best describes the Mayak dissolution rate, without introducing values for other parameters which conflict with other studies.

A Monte Carlo method for calculating Bayesian uncertainties in internal dosimetry.

This paper presents a novel Monte Carlo method (WeLMoS, Weighted Likelihood Monte-Carlo sampling method) that has been developed to perform Bayesian analyses of monitoring data. The WeLMoS method randomly samples parameters from continuous prior probability distributions and then weights each vector by its likelihood (i.e. its goodness of fit to the measurement data). Furthermore, in order to quality assure the method, and assess its strengths and weaknesses, a second method (MCMC, Markov chain Monte Carlo) has also been developed. The MCMC method uses the Metropolis algorithm to sample directly from the posterior distribution of parameters. The methods are evaluated and compared using an artificially generated case involving an exposure to a plutonium nitrate aerosol. In addition to calculating the uncertainty on internal dose, the methods can also calculate the probability distribution of model parameter values given the observed data. In other words, the techniques provide a powerful tool to obtain the estimates of parameter values that best fit the data and the associated uncertainty on these estimates. Current applications of the methodology, including the determination of lung solubility parameters, from volunteer and cohort data, are also discussed.

Internal dose assessments: uncertainty studies and update of ideas guidelines and databases within CONRAD project.

The work of Task Group 5.1 (uncertainty studies and revision of IDEAS guidelines) and Task Group 5.5 (update of IDEAS databases) of the CONRAD project is described. Scattering factor (SF) values (i.e. measurement uncertainties) have been calculated for different radionuclides and types of monitoring data using real data contained in the IDEAS Internal Contamination Database. Based upon this work and other published values, default SF values are suggested. Uncertainty studies have been carried out using both a Bayesian approach as well as a frequentist (classical) approach. The IDEAS guidelines have been revised in areas relating to the evaluation of an effective AMAD, guidance is given on evaluating wound cases with the NCRP wound model and suggestions made on the number and type of measurements required for dose assessment.

Internal dosimetry: towards harmonisation and coordination of research.

The CONRAD Project is a Coordinated Network for Radiation Dosimetry funded by the European Commission 6th Framework Programme. The activities developed within CONRAD Work Package 5 ('Coordination of Research on Internal Dosimetry') have contributed to improve the harmonisation and reliability in the assessment of internal doses. The tasks carried out included a study of uncertainties and the refinement of the IDEAS Guidelines associated with the evaluation of doses after intakes of radionuclides. The implementation and quality assurance of new biokinetic models for dose assessment and the first attempt to develop a generic dosimetric model for DTPA therapy are important WP5 achievements. Applications of voxel phantoms and Monte Carlo simulations for the assessment of intakes from in vivo measurements were also considered. A Nuclear Emergency Monitoring Network (EUREMON) has been established for the interpretation of monitoring data after accidental or deliberate releases of radionuclides. Finally, WP5 group has worked on the update of the existing IDEAS bibliographic, internal contamination and case evaluation databases. A summary of CONRAD WP5 objectives and results is presented here.

Estimating uncertainty on internal dose assessments.

The estimation of uncertainty on doses broadly falls into three categories. (1) Estimating the uncertainty on prospective doses. Here, the intake is known and the uncertainties in individual parameter values must be propagated through the calculated dose. (2) Estimating the error or uncertainty on dose assessments made from single measurements. Here, intake, model parameter and measurement uncertainties are propagated into the measurement, but default ICRP parameter values are used to estimate the intake and dose from the measurement. (3)Estimating the probability distribution of an individual's dose from a set of monitoring data. Here, Bayesian inference methods must be used to estimate the uncertainty on the estimated dose. A computer code is being developed that performs all three types of uncertainty analysis using Monte Carlo simulation. The software samples biokinetic parameters from probability density functions and then calculates doses from these parameters by calling the dosimetry code IMBA Professional Plus. A description of the methodology, together with an example application of the software, is included in this paper.

Avoiding biased estimates of dose when nothing is known about the time of intake.

A common problem in internal dosimetry occurs in routine monitoring, when it is required to estimate an intake from a measurement made at the end of a monitoring interval, and the time of intake is unknown. ICRP suggests that it should be assumed that the intake occurred in the middle of the monitoring period. However, it has been shown that this will, in the long-term, lead to biased estimates of a worker's intake and dose. In order to overcome this biasing, the United States Department of Energy (USDOE) recommends a different method based on calculating the intakes for all possible intake times in the interval and then taking an arithmetic average. In a recent paper, it has been shown that both the ICRP and USDOE methods were biased and that the only unbiased estimator of the true intake was obtained by assuming a constant chronic intake throughout the monitoring interval. In all of the analyses carried out to date on this 'Constant Chronic' method, it was assumed that the measurements were exact. In this paper, the effects of assuming either normally or log-normally distributed measurement errors are explored, and the effect on the bias of the intake estimate is investigated.

The autocorrelation coefficient as a tool for assessing goodness of fit between bioassay predictions and measurement data.

Project IDEAS has produced guidelines for internal dose assessment. An integral part of this process is assessing the goodness of fit of biokinetic models to bioassay data. It is recommended that a fit should only be accepted if (a) it is close enough to the data not to be rejected by a chi2 test and (b) if it looks acceptable to 'the eye'. The latter criterion was added to enable the assessor to reject fits which seemed to display some sort of systematic bias. However, there are problems with both of these tests: (a) the chi2 test is dependent on the assumed uncertainties which are often unknown, (b) 'by eye' assessment is subjective. In this paper, another statistic, the autocorrelation coefficient of the residuals, rho, is investigated. The main advantages of the rho statistic are that it is objective, very sensitive to biasing and independent of the assumed errors.

IDEAS internal contamination database: a compilation of published internal contamination cases. A tool for the internal dosimetry community.

In the scope of the IDEAS project to develop General Guidelines for the Assessment of Internal Dose from Monitoring data, two databases were compiled. The IDEAS Bibliography database contains references dealing with problems related to cases of internal contamination. The IDEAS Internal Contamination Database now contains more than 200 cases of internal contamination. In the near future, the IDEAS Internal Contamination database will be made available to the internal dosimetry community. The database has several potential applications, including: training, testing biokinetic models, testing software for calculating intakes and doses from bioassay data, comparison of data from a new accidental intake with that from previous exposures to similar materials. The database is by no means complete, and this presentation is also an appeal for internal contamination cases to extend and update it.

IMBA Professional Plus: a flexible approach to internal dosimetry.

IMBA (Integrated Modules for Bioassay Analysis) is a suite of software modules that implement the current ICRP biokinetic and dosimetric models for estimation of intakes and doses. The IMBA modules have gone through extensive quality assurance, and are now used for routine formal dose assessment by Approved Dosimetry Services throughout the UK. HPA has continued to develop the IMBA modules. In addition, several projects, sponsored by organisations both in the USA and in Canada, have resulted in the development of customised user-friendly interfaces (IMBA Expert 'editions'). These enable users not only to use the standard ICRP models, but also to change many of the parameter values from ICRP defaults, and to apply sophisticated data handling techniques to internal dose calculations. These include: fitting measurement data with the maximum likelihood method; using multiple chronic and acute intakes; and dealing with different data types, such as urine, faces and whole body simultaneously. These interfaces were improved further as a result of user-feedback, and a general 'off-the-shelf' product, IMBA Professional, was developed and made available in January 2004. A new version, IMBA Professional Plus, was released in April 2005, which is both faster and more powerful than previous software. The aim of this paper is to describe the capabilities of IMBA Professional Plus, and the mathematical methods used.

Evaluation of scattering factor values for internal dose assessment following the IDEAS guidelines: preliminary results.

The IDEAS Guidelines for the assessment of internal doses from monitoring data suggest default measurement uncertainties (i.e. scattering factors, SFs) to be used for different types of monitoring data. However, these default values were mainly based upon expert judgement. In this paper, SF values have been calculated for different radionuclides and types of monitoring data using real data contained in the IDEAS Internal Contamination Database. Results are presented.

Coordination of research on internal dosimetry in Europe: the CONRAD project.

The EUropean RAdiation DOSimetry Group (EURADOS) initiated in 2005 the CONRAD Project, a Coordinated Network for Radiation Dosimetry funded by the European Commission (EC), within the 6th Framework Programme (FP). The main purpose of CONRAD is to generate a European Network in the field of Radiation Dosimetry and to promote both research activities and dissemination of knowledge. The objective of CONRAD Work Package 5 (WP5) is the coordination of research on assessment and evaluation of internal exposures. Nineteen institutes from 14 countries participate in this action. Some of the activities to be developed are continuations of former European projects supported by the EC in the 5th FP (OMINEX and IDEAS). Other tasks are linked with ICRP activities, and there are new actions never considered before. A collaboration is established with CONRAD Work Package 4, dealing with Computational Dosimetry, to organise an intercomparison on Monte Carlo modelling for in vivo measurements of (241)Am deposited in a knee phantom. Preliminary results associated with CONRAD WP5 tasks are presented here.

The Mayak Worker Dosimetry System (MWDS-2013): How to Reduce Hyper-Realisations to Realisations.

Two important aspects in which the MWDS-2013 output (absorbed dose to organs calculated in each calendar year) differs from previous data bases (MWDS-2008 and DOSES-2005) are that they have been designed to (a) deal explicitly with uncertainties in model parameters, and (b) differentiate parameters that are considered to be shared (unknown, but having the same value for all workers) and unshared (unknown, but having different values between workers). A multiple-realisation approach is used to preserve information on the effects of shared and unshared parameters both for internal and external doses. Previously, a single realisation (a set of organ doses: one for each worker in the cohort) was calculated using the best estimates of parameter values only. In MWDS-2013, a set of 1000 realisations is produced, to reflect the uncertainty in assumed model parameters: each realisation using a different set of parameter values. Within each realisation, shared parameter values are fixed throughout the cohort, while unshared parameters are allowed to vary between workers. One problem is that because the calculation of organ dose is Bayesian, the estimate for each organ dose is not just a single value, but is itself a distribution (hyper-dose). Technically, it is the probability density of dose given the sampled set of parameter values and given the data for that worker. Thus, in our case, the realisations consist not of single doses, but distributions of doses. The term hyper-realisation is used to differentiate this from the more conventional realisation. Although the multiple hyper-realisation in principle contains all of the necessary information on parameter uncertainty, including shared and unshared parameters, in order to make preliminary epidemiological analyses tractable, and also for consistency with the external doses, it was required to convert the hyper-realisations to realisations. The aim of this paper is to discuss the different approaches that were considered to do this, and to define the method that was eventually chosen. Single spot (point) estimates of dose (for each worker) were also calculated to support the epidemiological analysis. The different methods for obtaining these and the implications are also discussed.

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.

THE MAYAK WORKER DOSIMETRY SYSTEM-2013 (MWDS-2013): PHASE II-QUALITY ASSURANCE OF ORGAN DOSE CALCULATIONS.

In order to check developed software tools, it was necessary to compare estimates of statistical characteristics of annual absorbed plutonium internal doses obtained by PANDORA and IMBA software with the same original data. The results were compared from dose calculations of five cases with different initial data on plutonium inhalation intake, lifetime measurements of plutonium activity in daily urine and post-mortem measurements in lungs, lung lymph nodes, liver and skeleton. Estimates of geometric mean and geometric standard deviation of annual regionally weighted lung dose and bone surface dose were compared. Satisfactory agreements of the estimates of statistical characteristics of annual doses to two critical organs for the selected cases were shown. One hundred individual hyper-realizations (forward model evaluations) are sufficient to calculate MWDS-2013 if only measurements of plutonium activity in daily urine are used, and 2000 individual hyper-realizations if both urine and autopsy measurement results are used.

The Mayak Worker Dosimetry System (Mwds-2013): Plutonium Dissolution in The Lungs-An Analysis of Mayak Workers.

Lung doses resulting from inhalation of plutonium aerosols are highly dependent on the assumed rate of particle clearance, which occurs by two competing processes: (1) particle transport clearance to the alimentary tract and to the thoracic lymph nodes and (2) clearance to systemic tissues, which occurs by dissolution of particles in lung fluid followed by uptake to blood, which is a process collectively known as absorption. Unbiased and accurate estimates of the values of lung absorption parameters are required to obtain reliable estimates of lung dose, particularly those inferred from urine bioassay. Parameter values governing the rate of absorption are best estimated from data, such as autopsy measurements of plutonium in the lungs and systemic tissues, which directly relate to the exposed workers of interest. However, because the mathematical models that determine clearance from the lungs and systemic tissues are complex and consist of many parameters, estimates of model parameter values are subject to significant uncertainties. With this in mind, this paper uses a Bayesian approach to estimate one of the most important dissolution parameters: the slow rate of dissolution. This is estimated for both plutonium nitrate and plutonium oxide bearing aerosols in the lungs of former workers of the Mayak Production Association. A value of 2.6 × 10-4 d-1 is estimated for plutonium nitrates, and 4.7 × 10-5 d-1 for plutonium oxides.

The Mayak Worker Dosimetry System (MWDS-2013): A Bayesian Analysis to Quantify Pulmonary Binding of Plutonium in Lungs Using Historic Beagle Dog Data.

The revised human respiratory tract model, published in Part 1 of the International Commission on Radiological Protection's (ICRP) report on Occupational Intakes of Radionuclides (OIR), includes a bound fraction, fb, to represent radionuclides that have become chemically bound in the lungs following dissolution of particulates in lung fluid. Bound radionuclides are not subject to particle transport clearance but can be absorbed to blood at a rate, sb. The occurrence of long-term binding of plutonium can greatly increase lung doses, particularly if it occurs in the bronchial and bronchiolar regions. However, there has been little evidence that currently supports the existence of a long-term bound state for plutonium. The present work describes the analysis of measurements of lung data obtained from a life span study of Beagle dogs that were exposed by inhalation to different concentrations of plutonium-239 (239Pu) nitrate aerosol at Pacific Northwest Laboratories, USA. The data have been analysed to assess whether a bound state was required to explain the data. A Bayesian approach was adopted for the analysis that accounts for uncertainties in model parameter values, including uncertainties in the rates of particle transport clearance. Furthermore, it performs the analysis using two different modelling hypotheses: a model based on the current ICRP human respiratory tract model and its treatment of alveolar particle transport clearance; and a model of particle transport clearance that is based on the updated model developed by ICRP to calculate dose coefficients for the OIR. The current model better represents clearance in dogs at early times (up to 1 year following intake) and the latter better represents retention at greater times (>5 years following intake). The results indicate that a long-term bound fraction of between 0.16 and 1.1%, with a mean value of between 0.24 and 0.8% (depending on the model) is required to explain the data.