Application of rodes software to experimental biokinetic data for dose assessment in mice and rats.

H Miloudi, M Locatelli, G Autret, D Balvay, A Desbrée, E Blanchardon, J M Bertho: application of RODES software to experimental biokinetic data for dose assessment in mice and rats. In support of experimental studies of chronic, long-term contamination in rodents, voxel-based computer models were built representing adult mice and juvenile, adult and elderly rats of both sexes. RODES software was created to calculate absorbed radiation doses to organs with these specific anatomical models. Absorbed doses were then calculated starting from previously published biokinetic data. Whole body doses showed less than 5% differences between calculation with RODES and calculation with the ICRP Publication 108 model for long term exposure to 90Sr of mice. Similar results were obtained for long term exposure to 137Cs. Dose distribution for 90Sr internal contamination also showed that the dose to the skeleton is six fold more as compared to the whole body dose while radiation dose to other organs is less than the mean whole body dose. These results underline the importance of using specific anatomical models according to the age and the sex of experimental animals.

The assessment and management of risks associated with exposures to short-range Auger- and beta-emitting radionuclides. State of the art and proposals for lines of research.

The assessment and management of risks associated with exposures to ionising radiation are defined by the general radiological protection system, proposed by the International Commission on Radiological Protection (ICRP). This system is regarded by a large majority of users as a robust system although there are a number of dissenting voices, claiming that it is not suitable for estimating the risks resulting from internal exposures. One of the specific issues of internal exposure involves short-range radiations such as Auger and beta particles. Auger- and beta-emitting radionuclides can be distributed preferentially in certain tissue structures and even in certain cellular organelles, according to their chemical nature and the vector with which they are associated. Given the limited range of the low-energy electrons in biological matter, this heterogeneous distribution can generate highly localised energy depositions and exacerbate radiotoxic responses at cellular level. These particularities in energy distribution and cellular responses are not taken into account by the conventional methods for the assessment of risk.Alternative systems have been proposed, based on dosimetry conducted at the cellular or even molecular level, whose purpose is to determine the energy deposition occurring within the DNA molecule. However, calculation of absorbed doses at the molecular level is not sufficient to ensure a better assessment of the risks incurred. Favouring such a microdosimetric approach for the risk assessments would require a comprehensive knowledge of the biological targets of radiation, the dose-response relationships at the various levels of organisation, and the mechanisms leading from cellular energy deposition to the appearance of a health detriment. The required knowledge is not fully available today and it is not yet possible to link an intracellular energy deposition to a probability of occurrence of health effects or to use methods based on cellular dosimetry directly.The imperfections of the alternative approaches proposed so far should not discourage efforts. Protection against exposure to Auger and low-energy beta emitters would benefit from mechanistic studies, dedicated to the study of energy depositions of the radionuclides in various cellular structures, but also from radiotoxicological studies to define the relative biological effectiveness of the various Auger emitters used in medicine and of certain low-energy beta emitters, whose behaviour may depend greatly on their chemical form during intake. The scientific expertise, as well as the human and physical resources needed to conduct these studies, is available. They could be now mobilised into international low-dose research programmes, in order to ultimately improve the protection of people exposed to these specific radionuclides.

Absorption of plutonium compounds in the respiratory tract.

In order to optimise the monitoring of potentially exposed workers, it is desirable to determine specific values of absorption for the compounds handled. This study derives specific values of absorption rates for different chemical forms of plutonium from in vitro and animal (monkeys, dogs, mice, rats) experiments, and from human contamination cases. Different published experimental data have been reinterpreted here to derive values for the absorption parameters, f(r), s(r) and s(s), used in the human respiratory tract model currently adopted by the International Commission on Radiological Protection (ICRP). The consequences of the use of these values were investigated by calculating related committed effective doses per unit intake. Average and median estimates were calculated for f(r), s(r), and s(s) for each plutonium compound, that can be used as default values for specific chemical forms instead of the current reference types. Nevertheless, it was shown that the use of the current ICRP reference absorption types provides reasonable approximations. Moreover, this work provides estimates of the variability in pulmonary absorption and, therefore, facilitates analyses of the uncertainties associated with assessments, either from bioassay measurements or from prospective calculations, of intake and dose.

ICRP Publication 141: Occupational Intakes of Radionuclides: Part 4.

The 2007 Recommendations (ICRP, 2007) introduced changes that affect the calculation of effective dose, and implied a revision of the dose coefficients for internal exposure, published previously in the Publication 30 series (ICRP, 1979a,b, 1980a, 1981, 1988) and Publication 68 (ICRP, 1994b). In addition, new data are now available that support an update of the radionuclide-specific information given in Publications 54 and 78 (ICRP, 1989a, 1997) for the design of monitoring programmes and retrospective assessment of occupational internal doses. Provision of new biokinetic models, dose coefficients, monitoring methods, and bioassay data was performed by Committee 2 and its task groups. A new series, the Occupational Intakes of Radionuclides (OIR) series, will replace the Publication 30 series and Publications 54, 68, and 78. OIR Part 1 (ICRP, 2015) describes the assessment of internal occupational exposure to radionuclides, biokinetic and dosimetric models, methods of individual and workplace monitoring, and general aspects of retrospective dose assessment. OIR Part 2 (ICRP, 2016), OIR Part 3 (ICRP, 2017), this current publication, and the final publication in the OIR series (OIR Part 5) provide data on individual elements and their radioisotopes, including information on chemical forms encountered in the workplace; a list of principal radioisotopes and their physical half-lives and decay modes; the parameter values of the reference biokinetic models; and data on monitoring techniques for the radioisotopes most commonly encountered in workplaces. Reviews of data on inhalation, ingestion, and systemic biokinetics are also provided for most of the elements. Dosimetric data provided in the printed publications of the OIR series include tables of committed effective dose per intake (Sv per Bq intake) for inhalation and ingestion, tables of committed effective dose per content (Sv per Bq measurement) for inhalation, and graphs of retention and excretion data per Bq intake for inhalation. These data are provided for all absorption types and for the most common isotope(s) of each element. The online electronic files that accompany the OIR series of publications contains a comprehensive set of committed effective and equivalent dose coefficients, committed effective dose per content functions, and reference bioassay functions. Data are provided for inhalation, ingestion, and direct input to blood. This fourth publication in the OIR series provides the above data for the following elements: lanthanum (La), cerium (Ce), praseodymium (Pr), neodymium (Nd), promethium (Pm), samarium (Sm), europium (Eu), gadolinium (Gd), terbium (Tb), dysprosium (Dy), holmium (Ho), erbium (Er), thulium (Tm), ytterbium (Yb), lutetium (Lu), actinium (Ac), protactinium (Pa), neptunium (Np), plutonium (Pu), americium (Am), curium (Cm), berkelium (Bk), californium (Cf), einsteinium (Es), and fermium (Fm).

Dosimetric models used in the Alpha-Risk project to quantify exposure of uranium miners to radon gas and its progeny.

The European project Alpha-Risk aims to quantify the cancer and non-cancer risks associated with multiple chronic radiation exposures by epidemiological studies, organ dose calculation and risk assessment. In the framework of this project, mathematical models have been applied to the organ dosimetry of uranium miners who are internally exposed to radon and its progeny as well as to long-lived radionuclides present in the uranium ore. This paper describes the methodology and the dosimetric models used to calculate the absorbed doses to specific organs arising from exposure to radon and its progeny in the uranium mines. The results of dose calculations are also presented.

Development, implementation and quality assurance of biokinetic models within CONRAD.

The work of the Task Group 5.2 'Research Studies on Biokinetic Models' of the CONRAD project is presented. New biokinetic models have been implemented by several European institutions. Quality assurance procedures included intercomparison of the results as well as quality assurance of model formulation. Additionally, the use of the models was examined leading to proposals of tuning parameters. Stable isotope studies were evaluated with respect to their implications to the new models, and new biokinetic models were proposed on the basis of their results. Furthermore, the development of a biokinetic model describing the effects of decorporation of actinides by diethylenetriaminepentaacetic acid treatment was initiated.

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.

EURADOS work on internal dosimetry.

European Radiation Dosimetry Group (EURADOS) Working Group 7 is a network on internal dosimetry that brings together researchers from more than 60 institutions in 21 countries. The work of the group is organised into task groups that focus on different aspects, such as development and implementation of biokinetic models (e.g. for diethylenetriamine penta-acetic acid decorporation therapy), individual monitoring and the dose assessment process, Monte Carlo simulations for internal dosimetry, uncertainties in internal dosimetry, and internal microdosimetry. Several intercomparison exercises and training courses have been organised. The IDEAS guidelines, which describe - based on the International Commission on Radiological Protection's (ICRP) biokinetic models and dose coefficients - a structured approach to the assessment of internal doses from monitoring data, are maintained and updated by the group. In addition, Technical Recommendations for Monitoring Individuals for Occupational Intakes of Radionuclides have been elaborated on behalf of the European Commission, DG-ENER (TECHREC Project, 2014-2016, coordinated by EURADOS). Quality assurance of the ICRP biokinetic models by calculation of retention and excretion functions for different scenarios has been performed and feedback was provided to ICRP. An uncertainty study of the recent caesium biokinetic model quantified the overall uncertainties, and identified the sensitive parameters of the model. A report with guidance on the application of ICRP biokinetic models and dose coefficients is being drafted at present. These and other examples of the group's activities, which complement the work of ICRP, are presented.

Dependence of the dose estimate on the time pattern of intake by the example of tritiated water intakes.

The uncertainties related to activity measurement and time pattern of intake in routine monitoring of internal exposure are considered through the example of tritiated water intakes. For this purpose, a combination of intake-to-bioassay and bioassay-to-intake calculations with Monte Carlo integration technique is introduced as a method of investigation. The time pattern of intake and the measured activity are defined as random input quantities. The probability density functions (PDFs) of the input quantities are defined and a Monte Carlo integration is performed to obtain the PDF of the output quantity which is either the value of intake estimated from a measured value of activity or the estimated activity from a given value of intake. Different possible estimates of the intake are considered: some represent the parameters of the PDF of the output quantity, others are derived from the commonly used constant chronic, I(CC), and mid-point, I(1/2), methods. The combinations of activity and intake estimates that would provide a stable estimate of the initial intake in intake-to-bioassay and bioassay-to-intake calculations were studied. Several intake estimates satisfying this requirement can be chosen depending on the task to be solved by adjusting the proper activity estimate.

Analysis of the uncertainty in internal dose estimate resulting from biological stochastic variability of excretion.

A method for investigating the uncertainty in internal dose estimate resulting from biological stochastic variability of excretion is proposed in the paper. The method is based on analysing generated cases of individual monitoring data using Monte Carlo simulation technique. In case of a single intake and assumption of stochastic variability of excretion is a single source of uncertainty it was shown that the intake (dose) uncertainty depends exclusively on the uncertainty of the bioassay data and the number of daily urine (faeces) measurements. Assuming a log-normal distribution for describing the variability of excretion a simple expression for calculating the uncertainty was proposed. In case of routine monitoring data it was shown that the uncertainty of annual intake (dose) estimate would depend on biological stochastic variability of excretion, type of excretion function and the number of monitoring intervals in a year. By the example of Pu and U aerosols it was shown that the effects of decreasing uncertainty in the dose estimate resulting from increasing the number of monitoring intervals in a year and from decreasing the uncertainty of bioassay data (performing a number of successive daily measurements, once in a year) should be estimated to optimise the routine monitoring program.

Some elements for a revision of the americium reference biokinetic model.

The interpretation of individual activity measurement after a contamination by 241Am or its parent nuclide 241Pu is based on the reference americium (Am) biokinetic model published by the International Commission on Radiological Protection in 1993 [International Commission on Radiological Protection. Age-dependent doses to members of the public from intake of radionuclides: Part 2 Ingestion dose coefficients. ICRP Publication 67. Ann. ICRP 23(3/4) (1993)]. The authors analysed the new data about Am biokinetics reported afterwards to propose an update of the current model. The most interesting results, from the United States Transuranium and Uranium Registries post-mortem measurement database [Filipy, R. E. and Russel, J. J. The United States Transuranium and Uranium Registries as sources for actinide dosimetry and bioeffects. Radiat. Prot. Dosim. 105(1-4), 185-187 (2003)] and the long-term follow-up of cases of inhalation intake [Malátová, I., Foltánová, S., Becková, V., Filgas, R., Pospísilová, H. and Hölgye, Z. Assessment of occupational doses from internal contamination with 241Am. Radiat. Prot. Dosim. 105(1-4), 325-328 (2003)], seemed to show that the current model underestimates the retention in the massive soft tissues and overestimates the retention in the skeleton and the late urinary excretion. However, a critical review of the data demonstrated that all were not equally reliable and suggested that only a slight revision of the model, possibly involving a change in the balance of activity between massive soft tissues, cortical and trabecular bone surfaces, may be required.

Automatic application of ICRP biokinetic models in voxel phantoms for in vivo counting and internal dose assessment.

As part of the improvement of calibration techniques of in vivo counting, the Laboratory of Internal Dose Assessment of the Institute of Radiological Protection and Nuclear Safety has developed a computer tool, 'OEDIPE', to model internal contamination, to simulate in vivo counting and to calculate internal dose. The first version of this software could model sources located in a single organ. As the distribution of the contamination evolves from the time of intake according to the biokinetics of the radionuclide, a new facility has been added to the software first to allow complex heterogeneous source modelling and then to automatically integrate the distribution of the contamination in the different tissues estimated by biokinetic calculation at any time since the intake. These new developments give the opportunity to study the influence of the biokinetics on the in vivo counting, leading to a better assessment of the calibration factors and the corresponding uncertainties.

Application of voxel phantoms in whole-body counting for the validation of calibration phantoms and the assessment of uncertainties.

This article is dedicated to the application of voxel phantoms in whole-body counting calibration. The first study was performed to validate this approach using IGOR, a physical phantom dedicated to fission and activation product (FAP) measurement, and a graphical user interface, developed at the IRSN internal dose assessment laboratory, called OEDIPE (French acronym for the tool for personalised internal dose assessment) associated with the Monte Carlo code MCNP. The method was validated by comparing the results of real measurements and simulations using voxel phantoms obtained from CT scan images of IGOR. To take this application further, two studies were carried out and are presented in this article. First, a comparison was made between the IGOR voxel based phantom (IGOVOX) and a voxel human body (Zubal Phantom) to confirm whether IGOR could be considered as a realistic representation of a human. Second, the errors made when considering sources homogeneously distributed in the body were assessed against real contamination by taking into account the biokinetic behaviour of the radioactive material for two modes of exposure: the ingestion of 137Cs in soluble form and the inhalation of insoluble 60Co several days after acute incorporation.

Estimation of the uncertainty in internal dose calculation for two contamination cases.

The assessment of internal dose is subject to a large uncertainty due to the limits of measuring technique and to the assumptions made by the expert. Here, we propose an approach to report the confidence interval associated with the evaluated dose. The sources of uncertainties considered so far include the date of intake, the physico-chemical characteristics of the radioactive material, the counting error and the stochastic variability of excretion. Three successive levels of approximation are suggested, depending on the expected dose, for which increasingly realistic parameter values should be sought and applied. Finally, the results of a Monte Carlo dose calculation are presented in the form of a statistical distribution of possible dose values. This approach has been applied to two cases of uranium and caesium exposure.

A structured approach for the assessment of internal dose: the IDEAS guidelines.

The need for harmonisation of the procedures for internal dose assessment has been recognised within an EU research project under the 5th Framework Programme. The aim of the IDEAS project was to develop general guidelines for standardising assessments of intakes and internal doses. It started in October 2001 and ended in June 2005. The project is closely related to some goals of the work of Committee 2 of the International Commission on Radiological Protection and since 2003 there has been close co-operation between the two groups. The general philosophy of the guidelines is focusing on the principles of harmonisation, accuracy and proportionality. The proposed system of 'level of task' to structure the approach of internal dose evaluation is also reported. Some details of the internal structure of the guidelines for the different pathways of intake are provided.

The work of the CONRAD task group 5.2: research studies on biokinetic models.

The objective of this Task Group is the coordination of research studies on biokinetic models and the evaluation of the implications of new biokinetic models on dose assessment and safety standards. For this the new ICRP models, which will be used for a revision of ICRP Publications 30, 54, 68 and 78, are implemented into six different computer codes in five European countries and quality assured by intercomparison procedures. The work has started with the implementation of the new ICRP Alimentary Tract Model. New systemic models and the new NCRP wound model will follow. The work also includes the evaluation of experimental results in terms of formulation by the new model structures and a quality assurance of model formulation.

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.

General guidelines for the assessment of internal dose from monitoring data: progress of the IDEAS project.

In recent major international intercomparison exercises on intake and internal dose assessments from monitoring data, the results calculated by different participants varied significantly. Based on this experience the need for harmonisation of the procedures has been formulated within an EU 5th Framework Programme research project. The aim of the project, IDEAS, is to develop general guidelines for standardising assessments of intakes and internal doses. The IDEAS project started in October 2001 and ended in June 2005. The project is closely related to some goals of the work of Committee 2 of the ICRP and since 2003 there has been close cooperation between the two groups. To ensure that the guidelines are applicable to a wide range of practical situations, the first step was to compile a database of well-documented cases of internal contamination. In parallel, an improved version of an existing software package was developed and distributed to the partners for further use. A large number of cases from the database was evaluated independently by the partners and the results reviewed. Based on these evaluations, guidelines were drafted and discussed with dosimetry professionals from around the world by means of a virtual workshop on the Internet early in 2004. The guidelines have been revised and refined on the basis of the experiences and discussions in this virtual workshop. The general philosophy of the Guidelines is presented here, focusing on the principles of harmonisation, optimisation and proportionality. Finally, the proposed Levels of Task to structure the approach of internal dose evaluation are reported.

Application of IDEAS guidelines: the IDEAS/IAEA intercomparison exercise on internal dose assessment.

As part of the EU Fifth Framework Programme IDEAS project 'General Guidelines for the Evaluation of Incorporation Monitoring Data', and in collaboration with the International Atomic Energy Agency, a new intercomparison exercise for the assessment of doses from intakes of radionuclides was organised. Several cases were selected, to cover a wide range of practices in the nuclear fuel cycle and medical applications. The cases were: (1) acute intake of HTO, (2) acute inhalation of the fission products 137Cs and 90Sr, (3) acute inhalation of 60Co, (4) repeated intakes of 131I, (5) intake of enriched uranium and (6) single intake of Pu isotopes and 241Am. This intercomparison exercise especially focused on the effect of the Guidelines proposed by the IDEAS project for harmonisation of internal dosimetry.