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Recently, several compilations of individual radiation epidemiology study results have aimed to obtain direct evidence on the magnitudes of dose-rate effects on radiation-related cancer risks. These compilations have relied on meta-analyses of ratios of risks from low dose-rate studies and matched risks from the solid cancer Excess Relative Risk models fitted to the acutely exposed Japanese A-bomb cohort. The purpose here is to demonstrate how choices of methodology for evaluating dose-rate effects on radiation-related cancer risks may influence the results reported for dose-rate effects. The current analysis is intended to address methodological issues and does not imply that the authors recommend a particular value for the dose and dose-rate effectiveness factor. A set of 22 results from one recent published study has been adopted here as a test set of data for applying the many different methods described here, that nearly all produced highly consistent results. Some recently voiced concerns, involving the recalling of the well-known theoretical point—the ratio of two normal random variables has a theoretically unbounded variance—that could potentially cause issues, are shown to be unfounded when aimed at the published work cited and examined in detail here. In the calculation of dose-rate effects for radiation protection purposes, it is recommended that meta-estimators should retain the full epidemiological and dosimetric matching information between the risks from the individual low dose-rate studies and the acutely exposed A-bomb cohort and that a regression approach can be considered as a useful alternative to current approaches.

The overall aim of this contribution to the 'Second Bill Morgan Memorial Special Issue' is to provide a high-level review of a recent report developed by a Committee for the National Council on Radiation Protection and Measurements (NCRP) titled 'Approaches for Integrating Information from Radiation Biology and Epidemiology to Enhance Low-Dose Health Risk Assessment'. It derives from previous NCRP Reports and Commentaries that provide the case for integrating data from radiation biology studies (available and proposed) with epidemiological studies (also available and proposed) to develop Biologically-Based Dose-Response (BBDR) models. In this review, it is proposed for such models to leverage the adverse outcome pathways (AOP) and key events (KE) approach for better characterizing radiation-induced cancers and circulatory disease (as the example for a noncancer outcome). The review discusses the current state of knowledge of mechanisms of carcinogenesis, with an emphasis on radiation-induced cancers, and a similar discussion for circulatory disease. The types of the various informative BBDR models are presented along with a proposed generalized BBDR model for cancer and a more speculative one for circulatory disease. The way forward is presented in a comprehensive discussion of the research needs to address the goal of enhancing health risk assessment of exposures to low doses of radiation. The use of an AOP/KE approach for developing a mechanistic framework for BBDR models of radiation-induced cancer and circulatory disease is considered to be a viable one based upon current knowledge of the mechanisms of formation of these adverse health outcomes and the available technical capabilities and computational advances. The way forward for enhancing low-dose radiation risk estimates will require there to be a tight integration of epidemiology data and radiation biology information to meet the goals of relevance and sensitivity of the adverse health outcomes required for overall health risk assessment at low doses and dose rates.

This paper summarises the view of the German Commission on Radiological Protection ("Strahlenschutzkommission", SSK) on the rationale behind the currently valid dose limits and dose constraints for workers recommended by the International Commission on Radiological Protection (ICRP). The paper includes a discussion of the reasoning behind current dose limits followed by a discussion of the detriment used by ICRP as a measure for stochastic health effects. Studies on radiation-induced cancer are reviewed because this endpoint represents the most important contribution to detriment. Recent findings on radiation-induced circulatory disease that are currently not included in detriment calculation are also reviewed. It appeared that for detriment calculations the contribution of circulatory diseases plays only a secondary role, although the uncertainties involved in their risk estimates are considerable. These discussions are complemented by a review of the procedures currently in use in Germany, or in discussion elsewhere, to define limits for genotoxic carcinogens. To put these concepts in perspective, actual occupational radiation exposures are exemplified with data from Germany, for the year 2012, and regulations in Germany are compared to the recommendations issued by ICRP. Conclusions include, among others, considerations on radiation protection concepts currently in use and recommendations of the SSK on the limitation of annual effective dose and effective dose cumulated over a whole working life.

An international intercomparison was organized by Working Group 7, Internal Dosimetry, of the European Radiation Dosimetry Group in collaboration with Working Group 6, Computational Dosimetry, for measurement and Monte Carlo simulation of Am-241 in three skull phantoms. The main objectives of this combined exercise were (1) comparison of the results of counting efficiency in fixed positions over each head phantom using different germanium detector systems, (2) calculation of the activity of Am-241 in the skulls, (3) comparison of Monte Carlo simulations with measurements (spectrum and counting efficiency), and (4) comparison of phantom performance. This initiative collected knowledge on equipment, detector arrangements, calibration procedures, and phantoms used around the world for in vivo monitoring of Am-241 in exposed persons, as well as on the Monte Carlo skills and tools of participants. Three skull phantoms (BfS, USTUR, and CSR phantoms) were transported from Europe (10 laboratories) to North America (United States and Canada). The BfS skull was fabricated with real human bone artificially labeled with Am-241. The USTUR skull phantom was made from the US Transuranium and Uranium Registries whole-body donor (case 0102) who was contaminated due to an occupational intake of Am-241; one-half of the skull corresponds to real contaminated bone, the other half is real human bone from a noncontaminated person. Finally, the CSR phantom was fabricated as a simple hemisphere of equivalent bone and tissue material. The three phantoms differ in weight, size, and shape, which made them suitable for an efficiency study. Based on their own skull calibration, the participants calculated the activity in the three European Radiation Dosimetry Group head phantoms. The Monte Carlo intercomparison was organized in parallel with the measurement exercise using the voxel representations of the three physical phantoms; there were 16 participants. Three tasks were identified with increasing difficulty: (1) Monte Carlo simulation of the simple CSR hemisphere and the Helmholz Zentrum Munchen high-purity germanium detector for calculating the counting efficiency for the 59.54 keV photons of Am-241, in established measurement geometry; (2) Monte Carlo simulation of particular measurement geometries using the BfS and USTUR voxel phantoms and the Helmholz Zentrum Munchen high-purity germanium detector detector; and (3) application of Monte Carlo methodology to calculate the calibration factor of each participant for the detector system and counting geometry (single or multidetector arrangement) to be used for monitoring a person in each in vivo facility, using complex skull phantoms. The results of both exercises resulted in the conclusion that none of the three available head phantoms is appropriate as a reference phantom for the calibration of germanium detection systems for measuring Am-241 in exposed adult persons. The main reasons for this are: (1) lack of homogeneous activity distribution in the bone material, or (2) inadequate shape/size for simulating an adult skull. Good agreement was found between Monte Carlo results and measurements, which supports Monte Carlo calibration of body counters as an alternative method when appropriate physical phantoms are not available and the detector and source are well known.

Tissue reactions and stochastic effects after exposure to ionising radiation are variable between individuals but the factors and mechanisms governing individual responses are not well understood. Individual responses can be measured at different levels of biological organization and using different endpoints following varying doses of radiation, including: cancers, non-cancer diseases and mortality in the whole organism; normal tissue reactions after exposures; and, cellular endpoints such as chromosomal damage and molecular alterations. There is no doubt that many factors influence the responses of people to radiation to different degrees. In addition to the obvious general factors of radiation quality, dose, dose rate and the tissue (sub)volume irradiated, recognized and potential determining factors include age, sex, life style (e.g., smoking, diet, possibly body mass index), environmental factors, genetics and epigenetics, stochastic distribution of cellular events, and systemic comorbidities such as diabetes or viral infections. Genetic factors are commonly thought to be a substantial contributor to individual response to radiation. Apart from a small number of rare monogenic diseases such as ataxia telangiectasia, the inheritance of an abnormally responsive phenotype among a population of healthy individuals does not follow a classical Mendelian inheritance pattern. Rather it is considered to be a multi-factorial, complex trait.

In order to quantify radiation risks at exposure scenarios relevant for radiation protection, often extrapolation of data obtained at high doses and high dose rates down to low doses and low dose rates is needed. Task Group TG91 on ‘Radiation Risk Inference at Low-dose and Low-dose Rate Exposure for Radiological Protection Purposes’ of the International Commission on Radiological Protection is currently reviewing the relevant cellular, animal and human studies that could be used for that purpose. This paper provides an overview of dose rates and doses typically used or present in those studies, and compares them with doses and dose rates typical of those received by the A-bomb survivors in Japan.

The biological effects on humans of low-dose and low-dose-rate exposures to ionizing radiation have always been of major interest. The most recent concept as suggested by the International Commission on Radiological Protection (ICRP) is to extrapolate existing epidemiological data at high doses and dose rates down to low doses and low dose rates relevant to radiological protection, using the so-called dose and dose-rate effectiveness factor (DDREF). The present paper summarizes what was presented and discussed by experts from ICRP and Japan at a dedicated workshop on this topic held in May 2015 in Kyoto, Japan. This paper describes the historical development of the DDREF concept in light of emerging scientific evidence on dose and dose-rate effects, summarizes the conclusions recently drawn by a number of international organizations (e.g., BEIR VII, ICRP, SSK, UNSCEAR, and WHO), mentions current scientific efforts to obtain more data on low-dose and low-dose-rate effects at molecular, cellular, animal and human levels, and discusses future options that could be useful to improve and optimize the DDREF concept for the purpose of radiological protection.

PURPOSE: Estimated radiation risks used for radiation protection purposes have been based primarily on the Life Span Study (LSS) of atomic bomb survivors who received brief exposures at high dose rates, many with high doses. Information is needed regarding radiation risks from low dose-rate (LDR) exposures to low linear-energy-transfer (low-LET) radiation. We conducted a meta-analysis of LDR epidemiologic studies that provide dose-response estimates of total solid cancer risk in adulthood in comparison to corresponding LSS risks, in order to estimate a dose rate effectiveness factor (DREF). MATERIALS AND METHODS: We identified 22 LDR studies with dose-response risk estimates for solid cancer after minimizing information overlap. For each study, a parallel risk estimate was derived from the LSS risk model using matching values for sex, mean ages at first exposure and attained age, targeted cancer types, and accounting for type of dosimetric assessment. For each LDR study a ratio of the excess relative risk per Gy (ERR Gy(-1)) to the matching LSS ERR risk estimate (LDR/LSS) was calculated, and a meta-analysis of the risk ratios was conducted. The reciprocal of the resultant risk ratio provided an estimate of the DREF. RESULTS: The meta-analysis showed a LDR/LSS risk ratio of 0.36 (95% confidence interval (CI) 0.14, 0.57) for the 19 studies of solid cancer mortality and 0.33 (95% CI 0.13, 0.54) when three cohorts with only incidence data also were added, implying a DREF with values around 3, but statistically compatible with 2. However, the analyses were highly dominated by the Mayak worker study. When the Mayak study was excluded the LDR/LSS risk ratios increased: 1.12 (95% CI 0.40, 1.84) for mortality and 0.54 (95% CI 0.09, 0.99) for mortality+incidence, implying a lower DREF in the range of 1 to 2. Meta-analyses that included only cohorts in which the mean dose was

International audience; ICRP suggested a strategy based on the distinction between a protection approach for dwellings and one for workplaces in the previous recommendations on radon. Now, the Commission recommends an integrated approach for the protection against radon exposure in all buildings irrespective of their purpose and the status of their occupants. The strategy of protection in buildings, implemented through a national action plan, is based on the application of the optimisation principle below a derived reference level in concentration (maximum 300 Bq m−3). A problem, however, arises that due to new epidemiological findings and application of dosimetric models, ICRP 115 (Ann ICRP 40, 2010) presents nominal probability coefficients for radon exposure that are approximately by a factor of 2 larger than in the former recommendations of ICRP 65 (Ann ICRP 23, 1993). On the basis of the so-called epidemiological approach and the dosimetric approach, the doubling of risk per unit exposure is represented by a doubling of the dose coefficients, while the risk coefficient of ICRP 103 (2007) remains unchanged. Thus, an identical given radon exposure situation with the new dose coefficients would result in a doubling of dose compared with the former values. This is of serious conceptual implications. A possible solution of this problem was presented during the workshop. © 2016, The Author(s).

Currently, most analyses of the A-bomb survivors' solid tumour and leukaemia data are based on a constant neutron relative biological effectiveness (RBE) value of 10 that is applied to all survivors, independent of their distance to the hypocentre at the time of bombing. The results of these analyses are then used as a major basis for current risk estimates suggested by the International Commission on Radiological Protection (ICRP) for use in international safety guidelines. It is shown here that (i) a constant value of 10 is not consistent with weighting factors recommended by the ICRP for neutrons and (ii) it does not account for the hardening of the neutron spectra in Hiroshima and Nagasaki, which takes place with increasing distance from the hypocentres. The purpose of this paper is to present new RBE values for the neutrons, calculated as a function of distance from the hypocentres for both cities that are consistent with the ICRP60 neutron weighting factor. If based on neutron spectra from the DS86 dosimetry system, these calculations suggest values of about 31 at 1000 m and 23 at 2000 m ground range in Hiroshima, while the corresponding values for Nagasaki are 24 and 22. If the neutron weighting factor that is consistent with ICRP92 is used, the corresponding values are about 23 and 21 for Hiroshima and 21 and 20 for Nagasaki, respectively. It is concluded that the current risk estimates will be subject to some changes in view of the changed RBE values. This conclusion does not change significantly if the new doses from the Dosimetry System DS02 are used.

Occupational exposures to ionising radiation mainly occur at low-dose rates and may accumulate effective doses of up to several hundred milligray. The objective of the present study is to evaluate the evidence of cancer risks from such low-dose-rate, moderate-dose (LDRMD) exposures. Our literature search for primary epidemiological studies on cancer incidence and mortality risks from LDRMD exposures included publications from 2002 to 2007, and an update of the UK National Registry for Radiation Workers study. For each (LDRMD) study we calculated the risk for the same types of cancer among the atomic bomb survivors with the same gender proportion and matched quantities for dose, mean age attained and mean age at exposure. A combined estimator of the ratio of the excess relative risk per dose from the LDRMD study to the corresponding value for the atomic bomb survivors was 1.21 (90% CI 0.51 to 1.90). The present analysis does not confirm that the cancer risk per dose for LDRMD exposures is lower than for the atomic bomb survivors. This result challenges the cancer risk values currently assumed for occupational exposures.

The European Commission has funded within its 6th Framework Programme a three-year project (2005–2007) called CONRAD, COordinated Network for RAdiation Dosimetry . A major task of the CONRAD Work Package “ complex mixed radiation fields at workplaces ” was to organise a benchmark exercise in a workplace field at a high-energy particle accelerator where neutrons are the dominant radiation component. The CONRAD benchmark exercise took place at the Gesellschaft fur Schwerionenforschung mbH (GSI) in Darmstadt, Germany in July 2006. In this paper, the results of the spectrometry using four extended -range Bonner sphere spectrometers of four different institutes are reported. Outside Cave A the neutron spectra were measured with three spectrometers at six selected positions and ambient dose equivalent values were derived for use in the intercomparison with other area monitors and dosemeters. At a common position all three spectrometers were used to allow a direct comparison of their results which acts as an internal quality assurance. The comparison of the neutron spectra measured by the different groups shows very good agreement. A detailed analysis presents some differences between the shapes of the spectra and possible sources of these differences are discussed. However, the ability of Bonner sphere spectrometers to provide reliable integral quantities like fluence and ambient dose equivalent is well demonstrated in this exercise. The fluence and dose results derived by the three groups agree very well within the given uncertainties, not only with respect to the total energy region present in this environment but also for selected energy regions which contribute in certain strength to the total values. In addition to the positions outside Cave A one spectrometer was used to measure the neutron spectrum at one position in the entry maze of Cave A. In this case a comparison was possible to earlier measurements.

Currently, EPR measurements are based on the assumption that odontogenesis (the series of events between the bud formation stage until the complete maturation of the tooth) is finished as soon as the tooth erupts. Consequently, it is also assumed that the hydroxyapatite concentration of the enamel (source of free radicals) does not depend on tooth age. However, the present work provides evidence that odontogenesis does not end after tooth eruption but continues for several years after eruption. Fifty-nine molars and pre-molars were analyzed by EPR spectroscopy. Tooth enamel samples were irradiated with different doses of gamma radiation from a 60Co source. The resulting EPR signals were evaluated in terms of posteruption tooth age and tooth position. It was found that, except for wisdom teeth, the concentration of the dosimetric EPR free radicals increased with tooth age after eruption and became constant after a certain period. A mathematical equation was developed to describe this effect as a function of tooth age, tooth position and applied dose. The results suggest that EPR measurements obtained on young teeth should be interpreted carefully unless data are available that would allow one to describe the effect of posteruptive enamel maturation on the EPR estimated dose quantitatively. Little or no correction is needed for older teeth. Since only a limited number of young teeth were available for the present study, further studies are needed to clarify the situation and quantify this effect.

Risk estimates for radiation-induced cancer are primarily based on the follow-up of the Japanese A-bomb survivors. Their exposures were due to gamma rays and neutrons, and, currently--with the assumed low RBE = 10 of neutrons and reference to the colon dose--the late radiation effects are almost fully attributed to the gamma rays. Solid cancer risk estimates for different organ sites are assessed here, and an inconspicuous but statistically highly significant trend of larger values is found for the organs closer to the body surface; i.e., the organs with less body shielding and, therefore, with larger neutron dose-fractions. Underestimation of the RBE of neutrons can explain this apparent correlation. The trend of ERR/Gy vs. depth ceases to be statistically significant for RBE values close to 100. The suggestion of high RBE values and the corresponding reduction of gamma-ray risk estimates is found to be in line with log-likelihood computations in terms of AMFIT, which provide for the solid cancer mortality of the A-bomb survivors the minimum deviance for RBE = 100 with a 95% confidence lower limit of 25. The present assessment had to use the data made publicly available by RERF. In this form they contain city-, sex-, age-, and dose-categories, but--instead of a separate neutron-dose category--only the mean neutron dose for each data cell. The tentative conclusions that are here obtained should, therefore, be examined by a more definitive analysis, either in terms of grouped data with a separate classification of neutron doses or, ideally, in terms of person by person calculations to be performed at RERF with individually estimated neutron doses.

A previous analysis of the solid cancer mortality data for 1950-1990 from the Japanese life-span study of the A-bomb survivors has assessed the solid cancer risk coefficients for gamma-rays in terms of the low dose risk coefficient ERR/Gy, i.e. the initial slope of the ERR vs. dose relation, and also in terms of the more precisely estimated intermediate dose risk coefficient, ERR(D1)/D1, for a reference dose, D1, which was chosen to be 1 Gy. The computations were performed for tentatively assumed values 20-50 of the neutron RBE against the reference dose and in terms of organ-averaged doses, rather than the traditionally applied colon doses. The resulting risk estimate for a dose of 1 Gy was about half as large as the most recent UNSCEAR estimate. The present assessment repeats the earlier analysis with two major extensions. It parallels computations based on organ-average doses with computations based on organ-specific doses and it updates the previous results by using the cancer mortality data for 1950-1997 which have recently been made available. With an assumed neutron RBE of 35, the resulting intermediate dose estimate of the lifetime attributable risk (LAR) for solid cancer mortality for a working population (ages 25-65 years) is 0.059/Gy with the attained-age model, and 0.044/Gy with the age-at-exposure model. For a population of all ages, 0.055/Gy is obtained with the attained-age model and 0.073/Gy with the age-at-exposure model. These values are up to about 20% higher than those obtained in the previous analysis with the 1950-1990 data. However, considerably more curvature in the dose-effect relation is now supported by the computations. A dose and dose-rate reduction factor DDREF=2 is now much more in line with the data than before. With this factor the LAR for a working population is--averaged over the age-at-exposure and the age-attained model--equal to 0.026/Gy. This is only half as large as the current ICRP estimate which is also based on the assumption DDREF=2.

Part I of this study presented an analysis of the solid cancer mortality data for 1950-1997 from the Japanese life-span study of the A-bomb survivors to assess the cancer risk for gamma-rays in terms of the organ-specific dose for all solid cancers combined. Compared to earlier analyses, considerably more curvature in the dose-effect relation is indicated by these computations, which now suggests a dose and dose-rate effectiveness factor of about 2. The computations are extended here in order to explore the site-specific solid cancer risks for various organs. A computational method has been developed whereby the site-specific cancer risks are all simultaneously computed with global age and gender effect modifiers. This provides a more parsimonious representation with fewer parameters and avoids the large relative standard errors which would otherwise result. The sensitivity of site-specific risks to the choices of the neutron RBE is examined. The site-specific risk estimates are quite sensitive to the neutron RBE for the least shielded organs such as the breast, bladder and oesophagus. For the deeper lying organs, such as the gallbladder, pancreas and uterus, the impact of the neutrons is much lower. With an assumed neutron RBE of 35, which is in line with results on low neutron doses in major past studies on rodents and which corresponds approximately to the current ICRP radiation weighting factor for neutrons, the neutrons appear to contribute about 40% of the observed excess cancer risk in the breast, i.e. the organ that is closest to the body surface. However, this neutron contribution fraction is only about 10% for deeper lying organs, such as the colon.

Quantification of biological effects (cancer, other diseases, and cell damage) associated with exposure to ionising radiation has been a major issue for the International Commission on Radiological Protection (ICRP) since its foundation in 1928. While there is a wealth of information on the effects on human health for whole-body doses above approximately 100 mGy, the effects associated with doses below 100 mGy are still being investigated and debated intensively. The current radiological protection approach, proposed by ICRP for workers and the public, is largely based on risks obtained from high-dose and high-dose-rate studies, such as the Japanese Life Span Study on atomic bomb survivors. The risk coefficients obtained from these studies can be reduced by the dose and dose-rate effectiveness factor (DDREF) to account for the assumed lower effectiveness of low-dose and low-dose-rate exposures. The 2007 ICRP Recommendations continue to propose a value of 2 for DDREF, while other international organisations suggest either application of different values or abandonment of the factor. This paper summarises the current status of discussions, and highlights issues that are relevant to reassessing the magnitude and application of DDREF.

241Am is known to he a bone-seeking isotope. In the long term it enters the human skeleton. In this paper, the case of a now 62 year old male subject who incorporated 241 Am in the early seventies, is used in order to compare state-of-the-art techniques for the detection of 241 Am in the human skeleton. The individual was measured using either partial (4 laboratories) or whole-body counters (I laboratory). The results of each laboratory are discussed separately. The skull measurements, performed by four laboratories, are in good agreement when using the same skull calibration phantom. Based on these results, the estimated total skeleton activity is in reasonable agreement with the result of a whole-body measurement performed by the fifth laboratory. A preliminary 241 Am skeleton burden of about 3.5 kBq is estimated for 1996.

Background The Monte Carlo code GEANT4 was used to implement first steps towards a treatment planning program for fast-neutron therapy at the FRM II research reactor in Garching, Germany. Depth dose curves were calculated inside a water phantom using measured primary neutron and simulated primary photon spectra and compared with depth dose curves measured earlier. The calculations were performed with GEANT4 in two different ways, simulating a simple box geometry and splitting this box into millions of small voxels (this was done to validate the voxelisation procedure that was also used to voxelise the human body). Results In both cases, the dose distributions were very similar to those measured in the water phantom, up to a depth of 30 cm. In order to model the situation of patients treated at the FRM II MEDAPP therapy beamline for salivary gland tumors, a human voxel phantom was implemented in GEANT4 and irradiated with the implemented MEDAPP neutron and photon spectra. The 3D dose distribution calculated inside the head of the phantom was similar to the depth dose curves in the water phantom, with some differences that are explained by differences in elementary composition. The lateral dose distribution was studied at various depths. The calculated cumulative dose volume histograms for the voxel phantom show the exposure of organs at risk surrounding the tumor. Conclusions In order to minimize the dose to healthy tissue, a conformal treatment is necessary. This can only be accomplished with the help of an advanced treatment planning system like the one developed here. Although all calculations were done for absorbed dose only, any biological dose weighting can be implemented easily, to take into account the increased radiobiological effectiveness of neutrons compared to photons.