Consideration of hereditary effects in the radiological protection system: evolution and current status.

PURPOSE: The purpose of this paper is to provide an overview of the methodology used to estimate radiation genetic risks and quantify the risk of hereditary effects as outlined in the ICRP Publication 103. It aims to highlight the historical background and development of the doubling dose method for estimating radiation-related genetic risks and its continued use in radiological protection frameworks. RESULTS: This article emphasizes the complexity associated with quantifying the risk of hereditary effects caused by radiation exposure and highlights the need for further clarification and explanation of the calculation method. As scientific knowledge in radiation sciences and human genetics continues to advance in relation to a number of factors including stability of disease frequency, selection pressures, and epigenetic changes, the characterization and quantification of genetic effects still remains a major issue for the radiological protection system of the International Commission on Radiological Protection. CONCLUSION: Further research and advancements in this field are crucial for enhancing our understanding and addressing the complexities involved in assessing and managing the risks associated with hereditary effects of radiation.

Cancer risk following low doses of ionising radiation - Current epidemiological evidence and implications for radiological protection.

Recent studies suggest that every year worldwide about a million patients might be exposed to doses of the order of 100 mGy of low-LET radiation, due to recurrent application of radioimaging procedures. This paper presents a synthesis of recent epidemiological evidence on radiation-related cancer risks from low-LET radiation doses of this magnitude. Evidence from pooled analyses and meta-analyses also involving epidemiological studies that, individually, do not find statistically significant radiation-related cancer risks is reviewed, and evidence from additional and more recent epidemiological studies of radiation exposures indicating excess cancer risks is also summarized. Cohorts discussed in the present paper include Japanese atomic bomb survivors, nuclear workers, patients exposed for medical purposes, and populations exposed environmentally to natural background radiation or radioactive contamination. Taken together, the overall evidence summarized here is based on studies including several million individuals, many of them followed-up for more than half a century. In summary, substantial evidence was found from epidemiological studies of exposed groups of humans that ionizing radiation causes cancer at acute and protracted doses above 100 mGy, and growing evidence for doses below 100 mGy. The significant radiation-related solid cancer risks observed at doses of several 100 mGy of protracted exposures (observed, for example, among nuclear workers) demonstrate that doses accumulated over many years at low dose rates do cause stochastic health effects. On this basis, it can be concluded that doses of the order of 100 mGy from recurrent application of medical imaging procedures involving ionizing radiation are of concern, from the viewpoint of radiological protection.

The use of dose quantities in radiological protection: ICRP publication 147 Ann ICRP 50(1) 2021.

The International Commission on Radiological Protection has recently published a report (ICRP Publication 147;Ann. ICRP50, 2021) on the use of dose quantities in radiological protection, under the same authorship as this Memorandum. Here, we present a brief summary of the main elements of the report. ICRP Publication 147 consolidates and clarifies the explanations provided in the 2007 ICRP Recommendations (Publication 103) but reaches conclusions that go beyond those presented in Publication 103. Further guidance is provided on the scientific basis for the control of radiation risks using dose quantities in occupational, public and medical applications. It is emphasised that best estimates of risk to individuals will use organ/tissue absorbed doses, appropriate relative biological effectiveness factors and dose-risk models for specific health effects. However, bearing in mind uncertainties including those associated with risk projection to low doses or low dose rates, it is concluded that in the context of radiological protection, effective dose may be considered as an approximate indicator of possible risk of stochastic health effects following low-level exposure to ionising radiation. In this respect, it should also be recognised that lifetime cancer risks vary with age at exposure, sex and population group. The ICRP report also concludes that equivalent dose is not needed as a protection quantity. Dose limits for the avoidance of tissue reactions for the skin, hands and feet, and lens of the eye will be more appropriately set in terms of absorbed dose rather than equivalent dose.

Modelling the bimodal distribution of indoor gamma-ray dose-rates in Great Britain.

Gamma radiation from naturally occurring sources (including directly ionizing cosmic-rays) is a major component of background radiation. An understanding of the magnitude and variation of doses from these sources is important, and the ability to predict them is required for epidemiological studies. In the present paper, indoor measurements of naturally occurring gamma-rays at representative locations in Great Britain are summarized. It is shown that, although the individual measurement data appear unimodal, the distribution of gamma-ray dose-rates when averaged over relatively small areas, which probably better represents the underlying distribution with inter-house variation reduced, appears bimodal. The dose-rate distributions predicted by three empirical and geostatistical models are also bimodal and compatible with the distributions of the areally averaged dose-rates. The distribution of indoor gamma-ray dose-rates in the UK is compared with those in other countries, which also tend to appear bimodal (or possibly multimodal). The variation of indoor gamma-ray dose-rates with geology, socio-economic status of the area, building type, and period of construction are explored. The factors affecting indoor dose-rates from background gamma radiation are complex and frequently intertwined, but geology, period of construction, and socio-economic status are influential; the first is potentially most influential, perhaps, because it can be used as a general proxy for local building materials. Various statistical models are tested for predicting indoor gamma-ray dose-rates at unmeasured locations. Significant improvements over previous modelling are reported. The dose-rate estimates generated by these models reflect the imputed underlying distribution of dose-rates and provide acceptable predictions at geographical locations without measurements.

Implications of recent epidemiologic studies for the linear nonthreshold model and radiation protection.

The recently published NCRP Commentary No. 27 evaluated the new information from epidemiologic studies as to their degree of support for applying the linear nonthreshold (LNT) model of carcinogenic effects for radiation protection purposes (NCRP 2018 Implications of Recent Epidemiologic Studies for the Linear Nonthreshold Model and Radiation Protection, Commentary No. 27 (Bethesda, MD: National Council on Radiation Protection and Measurements)). The aim was to determine whether recent epidemiologic studies of low-LET radiation, particularly those at low doses and/or low dose rates (LD/LDR), broadly support the LNT model of carcinogenic risk or, on the contrary, demonstrate sufficient evidence that the LNT model is inappropriate for the purposes of radiation protection. An updated review was needed because a considerable number of reports of radiation epidemiologic studies based on new or updated data have been published since other major reviews were conducted by national and international scientific committees. The Commentary provides a critical review of the LD/LDR studies that are most directly applicable to current occupational, environmental and medical radiation exposure circumstances. This Memorandum summarises several of the more important LD/LDR studies that incorporate radiation dose responses for solid cancer and leukemia that were reviewed in Commentary No. 27. In addition, an overview is provided of radiation studies of breast and thyroid cancers, and cancer after childhood exposures. Non-cancers are briefly touched upon such as ischemic heart disease, cataracts, and heritable genetic effects. To assess the applicability and utility of the LNT model for radiation protection, the Commentary evaluated 29 epidemiologic studies or groups of studies, primarily of total solid cancer, in terms of strengths and weaknesses in their epidemiologic methods, dosimetry approaches, and statistical modelling, and the degree to which they supported a LNT model for continued use in radiation protection. Recommendations for how to make epidemiologic radiation studies more informative are outlined. The NCRP Committee recognises that the risks from LD/LDR exposures are small and uncertain. The Committee judged that the available epidemiologic data were broadly supportive of the LNT model and that at this time no alternative dose-response relationship appears more pragmatic or prudent for radiation protection purposes.

An Assessment of Radiation-Associated Risks of Mortality from Circulatory Disease in the Cohorts of Mayak and Sellafield Nuclear Workers.

Mortality from circulatory disease (CD), ischemic heart disease (IHD) and cerebrovascular disease (CeVD) was investigated in relationship to cumulative doses of external gamma radiation and internal alpha radiation to the liver from deposited plutonium over long follow-up periods in two large cohorts of nuclear workers: the Russian Mayak Worker Cohort (MWC) and the UK Sellafield Worker Cohort (SWC). The MWC comprised 22,374 workers (74.6% males) with 5,123 CD deaths registered during 842,538 person-years of follow-up, while the SWC comprised 23,443 workers (87.8% males) with 2,322 CD deaths registered during 602,311 person-years of follow-up. Dose estimates for external gamma radiation and internal alpha radiation to the liver were calculated via a common methodology, in accordance with an agreed protocol. The mean cumulative external Hp(10) dose was 0.52 Sv for the MWC and 0.07 Sv for the SWC, while the mean cumulative internal dose was 0.19 Gy for the MWC and 0.01 Gy for the SWC. Categorical relative risks (RR) and excess relative risks (ERR) per unit dose were estimated for each cohort and for the pooled cohort when appropriate. The dose responses for CD, IHD and CeVD in relationship to internal alpha-particle dose did not differ significantly from the null for either the MWC, the SWC or the pooled plutonium worker cohort. The ERR/Sv estimates in relationship to external exposure were significantly raised for both cohorts (marginally so for the MWC) for CD and IHD (but not for CeVD), but differed significantly between the two cohorts, the estimate for the SWC being approximately ten times greater than that for the MWC. Examination of the ERR/Sv estimates for two periods of first employment at the two facilities revealed that the significant heterogeneity was confined to the earlier sub-cohorts, and that the estimates for the later sub-cohorts were compatible. The two sub-cohorts for the later first-employment periods were pooled, producing risk estimates that were raised, but not significantly so: ERR/Sv for CD, IHD and CeVD of 0.22 (95% CI: -0.01, 0.49), 0.22 (95% CI: -0.06, 0.57) and 0.24 (95% CI: -0.17, 0.80), respectively. The reasons for the complex pattern of results found in this study are unclear. Among potential explanations are the influence of differences in background CD mortality rates, an effect of other occupational factors, substantial uncertainties in doses, particularly during earlier periods of operations, as well as confounding and/or modifying factors that were not taken into account in the current analysis.

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.

Spatial prediction of naturally occurring gamma radiation in Great Britain.

Gamma radiation from natural sources is an important component of background radiation, and correlates with childhood leukaemia risk in Great Britain. The geographic variation of indoor gamma radiation dose-rates in Great Britain is explored using various geo-statistical methods. A multi-resolution Gaussian-process model using radial basis functions with 2, 4, or 8 components, is fitted via maximum likelihood, and a non-spatial model is also used, fitted by ordinary least squares. Because of the dataset size (N = 10,199), four other parametric spatial models are fitted by variogram-fitting. A randomly selected 70:30 split is used for fitting:validation. The models are evaluated based on their predictive performance as measured by Mean Absolute Error, Mean Squared Error, as well as Pearson correlation and rank-correlation between predicted and actual dose-rates. Each of the four parametric models (Matérn, Gaussian, Bessel, Spherical) fitted the empirical variogram well, and yielded similar predictions at >50 km separation, although with more substantial differences in predicted variograms at <50 km. The multi-resolution Gaussian-process model with 8 components had the best predictive accuracy among the models considered. The Spherical, Bessel, Matérn, Gaussian and ordinary least squares models had progressively worse predictive performance, the ordinary least squares model being particularly poor in this respect.

Use of effective dose.

International Commission on Radiological Protection (ICRP) Publication 103 provided a detailed explanation of the purpose and use of effective dose and equivalent dose to individual organs and tissues. Effective dose has proven to be a valuable and robust quantity for use in the implementation of protection principles. However, questions have arisen regarding practical applications, and a Task Group has been set up to consider issues of concern. This paper focusses on two key proposals developed by the Task Group that are under consideration by ICRP: (1) confusion will be avoided if equivalent dose is no longer used as a protection quantity, but regarded as an intermediate step in the calculation of effective dose. It would be more appropriate for limits for the avoidance of deterministic effects to the hands and feet, lens of the eye, and skin, to be set in terms of the quantity, absorbed dose (Gy) rather than equivalent dose (Sv). (2) Effective dose is in widespread use in medical practice as a measure of risk, thereby going beyond its intended purpose. While doses incurred at low levels of exposure may be measured or assessed with reasonable reliability, health effects have not been demonstrated reliably at such levels but are inferred. However, bearing in mind the uncertainties associated with risk projection to low doses or low dose rates, it may be considered reasonable to use effective dose as a rough indicator of possible risk, with the additional consideration of variation in risk with age, sex and population group.

Levels of naturally occurring gamma radiation measured in British homes and their prediction in particular residences.

Gamma radiation from natural sources (including directly ionising cosmic rays) is an important component of background radiation. In the present paper, indoor measurements of naturally occurring gamma rays that were undertaken as part of the UK Childhood Cancer Study are summarised, and it is shown that these are broadly compatible with an earlier UK National Survey. The distribution of indoor gamma-ray dose rates in Great Britain is approximately normal with mean 96 nGy/h and standard deviation 23 nGy/h. Directly ionising cosmic rays contribute about one-third of the total. The expanded dataset allows a more detailed description than previously of indoor gamma-ray exposures and in particular their geographical variation. Various strategies for predicting indoor natural background gamma-ray dose rates were explored. In the first of these, a geostatistical model was fitted, which assumes an underlying geologically determined spatial variation, superimposed on which is a Gaussian stochastic process with Matérn correlation structure that models the observed tendency of dose rates in neighbouring houses to correlate. In the second approach, a number of dose-rate interpolation measures were first derived, based on averages over geologically or administratively defined areas or using distance-weighted averages of measurements at nearest-neighbour points. Linear regression was then used to derive an optimal linear combination of these interpolation measures. The predictive performances of the two models were compared via cross-validation, using a randomly selected 70 % of the data to fit the models and the remaining 30 % to test them. The mean square error (MSE) of the linear-regression model was lower than that of the Gaussian-Matérn model (MSE 378 and 411, respectively). The predictive performance of the two candidate models was also evaluated via simulation; the OLS model performs significantly better than the Gaussian-Matérn model.

Residential mobility and associated factors in relation to the assessment of exposure to naturally occurring radiation in studies of childhood cancer.

Migration, that is the study subjects moving from one residential address to another, is a complication for epidemiological studies where exposures to the agent of interest depend on place of residence [corrected]. In this paper we explore migration in cases from a large British case-control study of childhood cancer and natural background radiation. We find that 44% of cases had not moved house between birth and diagnosis, and about two-thirds were living within 2 km of their residence at birth. The estimated dose at the diagnosis address was strongly correlated with that at the birth address, suggesting that use of just the birth address in this case-control study does not lead to serious bias in risk estimates. We also review other individual-based studies of naturally occurring radiation, with particular emphasis on those from Great Britain. Interview-based case-control and cohort studies can potentially establish full residential histories for study subjects and make direct measurements of radiation levels in the dwellings in question. However, in practice, because of study size and difficulties in obtaining adequate response rates, interview-based studies generally do not use full residential histories, and a substantial proportion of dose estimates often derive from models rather than direct measurements. More seriously, problems of incomplete response may lead to bias, not just to loss of power. Record-based case-control studies, which do not require direct contact with study subjects, avoid such problems, but at the expense of having only model-based exposure estimates that use databases of measurements.

A report from the 2013 international symposium: the evaluation of the effects of low-dose radiation exposure in the life span study of atomic bomb survivors and other similar studies.

The RERF International Low-Dose Symposium was held on 5-6 December 2013 at the RERF campus in Hiroshima, Japan, to discuss the issues facing the Life Span Study (LSS) and other low-dose studies. Topics included the current status of low-dose risk detection, strategies for low-dose epidemiological and statistical research, methods to improve communication between epidemiologists and biologists, and the current status of radiological studies and tools. Key points made by the participants included the necessity of pooling materials over multiple studies to gain greater insight where data from single studies are insufficient; generating models that reflect epidemiological, statistical, and biological principles simultaneously; understanding confounders and effect modifiers in the current data; and taking into consideration less studied factors such as the impact of dose rate. It is the hope of all participants that this symposium be used as a trigger for further studies, especially those using pooled data, in order to reach a greater understanding of the health effects of low-dose radiation.

A framework for estimating radiation-related cancer risks in Japan from the 2011 Fukushima nuclear accident.

We present here a methodology for health risk assessment adopted by the World Health Organization that provides a framework for estimating risks from the Fukushima nuclear accident after the March 11, 2011 Japanese major earthquake and tsunami. Substantial attention has been given to the possible health risks associated with human exposure to radiation from damaged reactors at the Fukushima Daiichi nuclear power station. Cumulative doses were estimated and applied for each post-accident year of life, based on a reference level of exposure during the first year after the earthquake. A lifetime cumulative dose of twice the first year dose was estimated for the primary radionuclide contaminants ((134)Cs and (137)Cs) and are based on Chernobyl data, relative abundances of cesium isotopes, and cleanup efforts. Risks for particularly radiosensitive cancer sites (leukemia, thyroid and breast cancer), as well as the combined risk for all solid cancers were considered. The male and female cumulative risks of cancer incidence attributed to radiation doses from the accident, for those exposed at various ages, were estimated in terms of the lifetime attributable risk (LAR). Calculations of LAR were based on recent Japanese population statistics for cancer incidence and current radiation risk models from the Life Span Study of Japanese A-bomb survivors. Cancer risks over an initial period of 15 years after first exposure were also considered. LAR results were also given as a percentage of the lifetime baseline risk (i.e., the cancer risk in the absence of radiation exposure from the accident). The LAR results were based on either a reference first year dose (10 mGy) or a reference lifetime dose (20 mGy) so that risk assessment may be applied for relocated and non-relocated members of the public, as well as for adult male emergency workers. The results show that the major contribution to LAR from the reference lifetime dose comes from the first year dose. For a dose of 10 mGy in the first year and continuing exposure, the lifetime radiation-related cancer risks based on lifetime dose (which are highest for children under 5 years of age at initial exposure), are small, and much smaller than the lifetime baseline cancer risks. For example, after initial exposure at age 1 year, the lifetime excess radiation risk and baseline risk of all solid cancers in females were estimated to be 0.7 · 10(-2) and 29.0 · 10(-2), respectively. The 15 year risks based on the lifetime reference dose are very small. However, for initial exposure in childhood, the 15 year risks based on the lifetime reference dose are up to 33 and 88% as large as the 15 year baseline risks for leukemia and thyroid cancer, respectively. The results may be scaled to particular dose estimates after consideration of caveats. One caveat is related to the lack of epidemiological evidence defining risks at low doses, because the predicted risks come from cancer risk models fitted to a wide dose range (0-4 Gy), which assume that the solid cancer and leukemia lifetime risks for doses less than about 0.5 Gy and 0.2 Gy, respectively, are proportional to organ/tissue doses: this is unlikely to seriously underestimate risks, but may overestimate risks. This WHO-HRA framework may be used to update the risk estimates, when new population health statistics data, dosimetry information and radiation risk models become available.

Childhood leukaemia risks: from unexplained findings near nuclear installations to recommendations for future research.

Recent findings related to childhood leukaemia incidence near nuclear installations have raised questions which can be answered neither by current knowledge on radiation risk nor by other established risk factors. In 2012, a workshop was organised on this topic with two objectives: (a) review of results and discussion of methodological limitations of studies near nuclear installations; (b) identification of directions for future research into the causes and pathogenesis of childhood leukaemia. The workshop gathered 42 participants from different disciplines, extending widely outside of the radiation protection field. Regarding the proximity of nuclear installations, the need for continuous surveillance of childhood leukaemia incidence was highlighted, including a better characterisation of the local population. The creation of collaborative working groups was recommended for consistency in methodologies and the possibility of combining data for future analyses. Regarding the causes of childhood leukaemia, major fields of research were discussed (environmental risk factors, genetics, infections, immunity, stem cells, experimental research). The need for multidisciplinary collaboration in developing research activities was underlined, including the prevalence of potential predisposition markers and investigating further the infectious aetiology hypothesis. Animal studies and genetic/epigenetic approaches appear of great interest. Routes for future research were pointed out.