E. Blanchardon

Lung Cancer Risk from Radon and Progeny and Statement on Radon

Recent epidemiological studies of the association between lung cancer and exposure to radon and its decay products are reviewed. Particular emphasis is given to pooled case-control studies of residential exposures, and to cohorts of underground miners exposed to relatively low levels of radon. The residential and miner epidemiological studies provide consistent estimates of the risk of lung cancer, with significant associations observed at average annual concentrations of approximately 200 Bq/m³ and cumulative occupational levels of approximately 50 working level months (WLM), respectively. Based on recent results from combined analyses of epidemiological studies of miners, a lifetime excess absolute risk of 5 × 10⁻⁴ per WLM [14 × 10⁻⁵ per (mJh/m³)] should now be used as the nominal probability coefficient for radon- and radon-progeny-induced lung cancer, replacing the previous Publication 65 (ICRP, 1993) value of 2.8 × 10⁻⁴ per WLM [8 × 10⁻⁵ per (mJh/m³)]. Current knowledge of radon-associated risks for organs other than the lungs does not justify the selection of a detriment coefficient different from the fatality coefficient for radon-induced lung cancer. Publication 65 (ICRP, 2003) recommended that doses from radon and its progeny should be calculated using a dose conversion convention based on epidemiological data. It is now concluded that radon and its progeny should be treated in the same way as other radionuclides within the ICRP system of protection; that is, doses from radon and its progeny should be calculated using ICRP biokinetic and dosimetric models. ICRP will provide dose coefficients per unit exposure to radon and its progeny for different reference conditions of domestic and occupational exposure, with specified equilibrium factors and aerosol characteristics.

Ionizing radiation biomarkers for potential use in epidemiological studies

Ionizing radiation is a known human carcinogen that can induce a variety of biological effects depending on the physical nature, duration, doses and dose-rates of exposure. However, the magnitude of health risks at low doses and dose-rates (below 100mSv and/or 0.1mSvmin(-1)) remains controversial due to a lack of direct human evidence. It is anticipated that significant insights will emerge from the integration of epidemiological and biological research, made possible by molecular epidemiology studies incorporating biomarkers and bioassays. A number of these have been used to investigate exposure, effects and susceptibility to ionizing radiation, albeit often at higher doses and dose rates, with each reflecting time-limited cellular or physiological alterations. This review summarises the multidisciplinary work undertaken in the framework of the European project DoReMi (Low Dose Research towards Multidisciplinary Integration) to identify the most appropriate biomarkers for use in population studies. In addition to logistical and ethical considerations for conducting large-scale epidemiological studies, we discuss the relevance of their use for assessing the effects of low dose ionizing radiation exposure at the cellular and physiological level. We also propose a temporal classification of biomarkers that may be relevant for molecular epidemiology studies which need to take into account the time elapsed since exposure. Finally, the integration of biology with epidemiology requires careful planning and enhanced discussions between the epidemiology, biology and dosimetry communities in order to determine the most important questions to be addressed in light of pragmatic considerations including the appropriate population to be investigated (occupationally, environmentally or medically exposed), and study design. The consideration of the logistics of biological sample collection, processing and storing and the choice of biomarker or bioassay, as well as awareness of potential confounding factors, are also essential.

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.

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.

Application of the ICRP/ICRU reference computational phantoms to internal dosimetry: calculation of specific absorbed fractions of energy for photons and electrons

The emission of radiation from a contaminated body region is connected with the dose received by radiosensitive tissue through the specific absorbed fractions (SAFs) of emitted energy, which is therefore an essential quantity for internal dose assessment. A set of SAFs were calculated using the new adult reference computational phantoms, released by the International Commission on Radiological Protection (ICRP) together with the International Commission on Radiation Units and Measurements (ICRU). Part of these results has been recently published in ICRP Publication 110 (2009 Adult reference computational phantoms (Oxford: Elsevier)). In this paper, we mainly discuss the results and also present them in numeric form. The emission of monoenergetic photons and electrons with energies ranging from 10 keV to 10 MeV was simulated for three source organs: lungs, thyroid and liver. SAFs were calculated for four target regions in the body: lungs, colon wall, breasts and stomach wall. For quality assurance purposes, the simulations were performed simultaneously at the Helmholtz Zentrum München (HMGU, Germany) and at the Institute for Radiological Protection and Nuclear Safety (IRSN, France), using the Monte Carlo transport codes EGSnrc and MCNPX, respectively. The comparison of results shows overall agreement for photons and high-energy electrons with differences lower than 8%. Nevertheless, significant differences were found for electrons at lower energy for distant source/target organ pairs. Finally, the results for photons were compared to the SAF values derived using mathematical phantoms. Significant variations that can amount to 200% were found. The main reason for these differences is the change of geometry in the more realistic voxel body models. For electrons, no SAFs have been computed with the mathematical phantoms; instead, approximate formulae have been used by both the Medical Internal Radiation Dose committee (MIRD) and the ICRP due to the limitations imposed by the computing power available at this time. These approximations are mainly based on the assumption that electrons are absorbed locally in the source organ itself. When electron SAFs are calculated explicitly, discrepancies with this simplifying assumption are notable, especially at high energies and for neighboring organs where the differences can reach the same order of magnitude as for photon SAFs.

Ionizing radiation biomarkers in epidemiological studies - an update.

Recent epidemiology studies highlighted the detrimental health effects of exposure to low dose and low dose rate ionizing radiation (IR): nuclear industry workers studies have shown increased leukaemia and solid tumour risks following cumulative doses of <100mSv and dose rates of <10mGy per year; paediatric patients studies have reported increased leukaemia and brain tumours risks after doses of 30-60mGy from computed tomography scans. Questions arise, however, about the impact of even lower doses and dose rates where classical epidemiological studies have limited power but where subsets within the large cohorts are expected to have an increased risk. Further progress requires integration of biomarkers or bioassays of individual exposure, effects and susceptibility to IR. The European DoReMi (Low Dose Research towards Multidisciplinary Integration) consortium previously reviewed biomarkers for potential use in IR epidemiological studies. Given the increased mechanistic understanding of responses to low dose radiation the current review provides an update covering technical advances and recent studies. A key issue identified is deciding which biomarkers to progress. A roadmap is provided for biomarker development from discovery to implementation and used to summarise the current status of proposed biomarkers for epidemiological studies. Most potential biomarkers remain at the discovery stage and for some there is sufficient evidence that further development is not warranted. One biomarker identified in the final stages of development and as a priority for further research is radiation specific mRNA transcript profiles.

Dose Conversion Factors For Radon: Recent Developments

Epidemiological studies of the occupational exposure of miners and domestic exposures of the public have provided strong and complementary evidence of the risks of lung cancer following inhalation of radon progeny. Recent miner epidemiological studies, which include low levels of exposure, long duration of follow-up, and good quality of individual exposure data, suggest higher risks of lung cancer per unit exposure than assumed previously by the International Commission on Radiological Protection (ICRP). Although risks can be managed by controlling exposures, dose estimates are required for the control of occupational exposures and are also useful for comparing sources of public exposure. Currently, ICRP calculates doses from radon and its progeny using dose conversion factors from exposure (WLM) to dose (mSv) based on miner epidemiological studies, referred to as the epidemiological approach. Revision of these dose conversion factors using risk estimates based on the most recent epidemiological data gives values that are in good agreement with the results of calculations using ICRP biokinetic and dosimetric models, the dosimetric approach. ICRP now proposes to treat radon progeny in the same way as other radionuclides and to publish dose coefficients calculated using models, for use within the ICRP system of protection.

Risk of Lung Cancer Mortality in Relation to Lung Doses among French Uranium Miners: Follow-Up 1956–1999

The aim of this study was to assess the risk of lung cancer death associated with cumulative lung doses from exposure to α-particle emitters, including radon gas, radon short-lived progeny, and long-lived radionuclides, and to external γ rays among French uranium miners. The French “post-55” sub-cohort included 3,377 uranium miners hired from 1956, followed up through the end of 1999, and contributing to 89,405 person-years. Lung doses were calculated with the ICRP Human Respiratory Tract Model (Publication 66) for 3,271 exposed miners. The mean “absorbed lung dose” due to α-particle radiation was 78 mGy, and that due to the contribution from other types of radiation (γ and β-particle radiation) was 56 mGy. Radon short-lived progeny accounted for 97% of the α-particle absorbed dose. Out of the 627 deaths, the cause of death was identified for 97.4%, and 66 cases were due to lung cancer. A significant excess relative risk (ERR) of lung cancer death was associated with the total absorbed lung dose (ERR/Gy = 2.94, 95% CI 0.80, 7.53) and the α-particle absorbed dose (4.48, 95% CI 1.27, 10.89). Assuming a value of 20 for the relative biological effectiveness (RBE) of α particles for lung cancer induction, the ERR/Gy-Eq for the total weighted lung dose was 0.22 (95% CI: 0.06, 0.53).

EURADOS-IDEAS GUIDELINES (VERSION 2) FOR THE ESTIMATION OF COMMITTED DOSES FROM INCORPORATION MONITORING DATA.

Dose assessment after intakes of radionuclides requires application of biokinetic and dosimetric models and assumptions about factors influencing the final result. In 2006, a document giving guidance for such assessment was published, commonly referred to as the IDEAS Guidelines. Following its publication, a working group within the European networks CONRAD and EURADOS was established to improve and update the IDEAS Guidelines. This work resulted in Version 2 of the IDEAS Guidelines, which was published in 2013 in the form of a EURADOS report. The general structure of the original document was maintained; however, new procedures were included, e.g. the direct dose assessment method for (3)H or special procedure for wound cases applying the NCRP wound model. In addition, information was updated and expanded, e.g. data on dietary excretion of U, Th, Ra and Po for urine and faeces or typical and achievable values for detection limits for different bioassay measurement techniques.

Biokinetic modelling of DTPA decorporation therapy: the CONRAD approach

Administration of diethylene triamine pentaacetic acid (DTPA) can enhance the urinary excretion rate of plutonium (Pu) for several days, but most of this Pu decorporation occurs on the first day after treatment. The development of a biokinetic model describing the mechanisms of decorporation of actinides by administration of DTPA was initiated as a task of the coordinated network for radiation dosimetry project. The modelling process was started by using the systemic biokinetic model for Pu from Leggett et al. and the biokinetic model for DTPA compounds of International Commission on Radiation Protection Publication 53. The chelation of Pu and DTPA to Pu-DTPA was treated explicitly and is assumed to follow a second-order process. It was assumed that the chelation takes place in the blood and in the rapid turnover soft tissues compartments of the Pu model, and that Pu-DTPA behaves in the same way as administered DTPA. First applications of this draft model showed that the height of the peak of urinary excretion after administration of DTPA was determined by the chelation rate. However, repetitions of DTPA administration shortly after the first one showed no effect in the application of the draft model in contrast to data from real cases. The present draft model is thus not yet realistic. Therefore several questions still have to be answered, notably about where the Pu-DTPA complexes are formed, which biological ligands of Pu are dissociated, if Pu-DTPA is stable and if the biokinetics of Pu-DTPA excretion is similar to that of DTPA. Further detailed studies of human contamination cases and experimental data about Pu-DTPA kinetics will be needed in order to address these issues. The work will now be continued within a working group of EURADOS.