Radiation detriment calculation methodology: summary of ICRP Publication 152.

Radiation detriment is a concept to quantify the burden of stochastic effects from exposure of the human population to low-dose and/or low-dose-rate ionising radiation. As part of a thorough review of the system of radiological protection, the International Commission on Radiological Protection (ICRP) has compiled a report on radiation detriment calculation methodology as Publication 152. It provides a historical review of the detriment calculation with details of the procedure used in ICRP Publication 103. A selected sensitivity analysis was conducted to identify the parameters and calculation conditions that can be major sources of variation and uncertainty. It has demonstrated that sex, age at exposure, dose and dose-rate effectiveness factor, dose assumption in the lifetime risk calculation, and lethality fraction have a substantial impact on the calculated values of radiation detriment. Discussions are also made on the issues to be addressed and possible ways for improvement toward the revision of general recommendations. These include update of the reference population data and cancer severity parameters, revision of cancer risk models, and better handling of the variation with sex and age. Finally, emphasis is placed on transparency and traceability of the calculation, along with the need to improve the way of expressing and communicating the detriment.

History of radiation detriment and its calculation methodology used in ICRP Publication 103.

Over the past decades, the International Commission on Radiological Protection (ICRP) has used radiation detriment, which is a multidimensional concept to quantify the overall harm to health from stochastic effects of low-level radiation exposure of different parts of the body. Each tissue-specific detriment is determined from the nominal tissue-specific risk coefficient, weighted by the severity of the disease in terms of lethality, impact on quality of life and years of life lost. Total detriment is the sum of the detriments for separate tissues and organs. Tissue weighting factors for the calculation of effective dose are based on relative contributions of each tissue to the total detriment. Calculating radiation detriment is a complex process that requires information from various sources and judgements on how to achieve calculations. As such, it is important to document its calculation methodology. To improve the traceability of calculations and form a solid basis for future recommendations, the ICRP Task Group 102 on detriment calculation methodology was established in 2016. As part of its mission, the history of radiation detriment was reviewed, and the process of detriment calculation was detailed. This article summarises that work, aiming to clarify the methodology of detriment calculation currently used by ICRP.

Effect of age-related baseline risk on radiation dose response for coronary heart disease.

We attempted to estimate the mortality risk of radiation-associated coronary heart disease (CHD) by using a model in which radiation was assumed to participate in the atherosclerotic process jointly with ageing. Model parameters were determined by fitting the Life Span Study data of atomic bomb survivors. According to the model, the excess relative risk (ERR) varies depending on the baseline risk; when applied to the death statistics of Japan and the USA, the estimated ERR was consistently higher in the Japanese population. The absolute risk showed an opposite trend, such that the estimated lifetime attributable risk was approximately two times higher in the US population. Excess cases were expected to appear in old age almost synchronously with spontaneous cases; in contrast, the risk is practically unnoticeable for those young to middle aged. Our model suggests that the radiation dose-response curve for CHD, as well as the latency in epidemiological studies, could be modified by the baseline risk.

Dose and dose-rate effects of ionizing radiation: a discussion in the light of radiological protection.

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.

Time-integrated radiation risk metrics and interpopulation variability of survival.

Task Group 115 of the International Commission on Radiological Protection is focusing on mission-related exposures to space radiation and concomitant health risks for space crew members including, among others, risk of cancer development. Uncertainties in cumulative radiation risk estimates come from the stochastic nature of the considered health outcome (i.e., cancer), uncertainties of statistical inference and model parameters, unknown secular trends used for projections of population statistics and unknown variability of survival properties between individuals or population groups. The variability of survival is usually ignored when dealing with large groups, which can be assumed well represented by the statistical data for the contemporary general population, either in a specific country or world averaged. Space crew members differ in many aspects from individuals represented by the general population, including, for example, their lifestyle and health status, nutrition, medical care, training and education. The individuality of response to radiation and lifespan is explored in this modelling study. Task Group 115 is currently evaluating applicability and robustness of various risk metrics for quantification of radiation-attributed risks of cancer for space crew members. This paper demonstrates the impact of interpopulation variability of survival curves on values and uncertainty of the estimates of the time-integrated radiation risk of cancer.

A report from the 2013 international workshop: radiation and cardiovascular disease, Hiroshima, Japan.

Two longitudinal cohort studies of Japanese atomic bomb survivors-the life span study (LSS) and the adult health study (AHS)-from the Radiation Effects Research Foundation (RERF) indicate that total body irradiation doses less than 1 Gy are associated with an increased risk of cardiovascular disease (CVD), but several questions about this association remain.In particular, the diversity of heart disease subtypes and the high prevalence of other risk factors complicate the estimates of radiation effects. Subtype-specific analyses with more reliable diagnostic criteria and measurement techniques are needed. The radiation effects on CVD risk are probably tissue-reaction (deterministic) effects, so the dose-response relationships for various subtypes of CVD may be nonlinear and therefore should be explored with several types of statistical models.Subpopulations at high risk need to be identified because effects at lower radiation doses may occur primarily in these susceptible subpopulations. Whether other CVD risk factors modify radiation effects also needs to be determined. Finally, background rates for various subtypes of CVD have historically differed substantially between Japanese and Western populations, so the generalisability to other populations needs to be examined.Cardiovascular disease mechanisms and manifestations may differ between high-dose local irradiation and low-dose total body irradiation (TBI)-microvascular damage and altered metabolism from low-dose TBI, but coronary artery atherosclerosis and thrombotic myocardial infarcts at high localised doses. For TBI, doses to organs other than the heart may be important in pathogenesis of CVD, so data on renal and liver disorders, plaque instability, microvascular damage, metabolic disorders, hypertension and various CVD biomarkers and risk factors are needed. Epidemiological, clinical and experimental studies at doses of less than 1 Gy are necessary to clarify the effects of radiation on CVD risk.

Sensitivity analysis of parameters and methodological choices used in calculation of radiation detriment for solid cancer.

Purpose: Radiation detriment is a concept used by the International Commission on Radiological Protection (ICRP) to quantify the harmful health effects of radiation exposure in humans. The current approach of radiation detriment calculation has been defined in ICRP Publication 103 in 2007. It is determined from lifetime risk of cancer and heritable effects for a composite reference population, taking into account the severity of the disease in terms of lethality, quality of life and years of life lost. Many parameters are used in the calculations and the variation of these parameters can have effects on the cancer detriment, which needs to be investigated.Materials and methods: In this paper, we conducted a sensitivity analysis for examining the impact of 12 different parameters or methodological choices on the calculation of solid cancer detriment, such as the lifetime risk calculation method, survival curve, dose and dose-rate effectiveness factor (DDREF), age-at-exposure, sex, reference population, risk transfer model, latency, attained age, lethality, minimum quality of life factor and relative cancer-free life lost. Sensitivity calculations have been performed systematically for each of 10 solid cancer sites, by changing each one of the parameters in turn.Results: This sensitivity analysis demonstrated a large impact on estimated detriment from DDREF, age-at-exposure, sex and lethality, a noticeable impact of risk transfer model associated to variation of baseline rates, and a limited impact of risk calculation method, survival curve, latency, attained age, quality of life and relative years of life lost.Conclusion: These results could have implications for radiation protection standards, and they should help define priorities for future research in the field of low radiation dose and dose rate research. The present sensitivity analysis is part of a global effort of ICRP to review the bases of radiation detriment calculation and assess potential evolutions to improve the radiation protection system.

DNA double-strand breaks induced by very low X-ray doses are largely due to bystander effects.

Phosphorylated ATM immunofluorescence staining was used to investigate the dose-response relationship for the number of DNA double-strand breaks (DSBs) induced in primary normal human fibroblasts irradiated with doses from 1.2 to 200 mGy. The induction of DSBs showed a supralinear dose-response relationship. Radiation-induced bystander effects may explain these findings. To test this hypothesis, the number of DSBs in cells treated with lindane, an inhibitor of radiation-induced bystander effects, prior to X irradiation was assessed; a supralinear dose-response relationship was not observed. Moreover, the number of DSBs obtained by subtracting the number of phosphorylated ATM foci in lindane-treated cells from the number of phosphorylated ATM foci in untreated cells was proportional to the dose at low doses (1.2-5 mGy) and was saturated at doses from 10-200 mGy. Thus the increase in the number of DSBs in the range of 1.2-5 mGy was largely due to radiation-induced bystander effects, while at doses >10 mGy, the DSBs may be induced mainly by dose-dependent direct radiation effects and partly by dose-independent radiation-induced bystander effects. The findings in our present study provide direct evidence of the dose-response relationship for radiation-induced bystander effects from broad-beam X rays.

Early and Delayed Induction of DSBs by Nontargeted Effects in ICR Mouse Lymphocytes after In Vivo X Irradiation.

The goal of this study was to determine whether in vivo X irradiation induces nontargeted effects, such as delayed effects and bystander effects in ICR mouse lymphocytes. We first examined the generation of DNA double-strand breaks (DSBs) in lymphocytes, isolated from ICR mice exposed to 1 Gy X irradiation, by enumeration of p53 binding protein 1 (53BP1) foci, and observed that the number of 53BP1 foci reached their maximum 3 days postirradiation and decreased to background level 30 days postirradiation. However, the number of 53BP1 foci was significantly increased in lymphocytes isolated from ICR mice 90-365 days postirradiation. This result indicates that in vivo X irradiation induced delayed DSBs in ICR mouse lymphocytes. We next counted the number of 53BP1 foci in lymphocytes isolated from sham-irradiated ICR mice that had been co-cultured with lymphocytes isolated from 1 Gy X-irradiated ICR mice, and observed a significant increase in the number of 53BP1 foci 1-7 days postirradiation. This result indicates that in vivo X irradiation induced bystander effects in ICR mouse lymphocytes. These findings suggest that in vivo X irradiation induces early and delayed nontargeted effects in ICR mouse lymphocytes.

Numerical Analysis of Organ Doses Delivered During Computed Tomography Examinations Using Japanese Adult Phantoms with the WAZA-ARI Dosimetry System.

A dosimetry system for computed tomography (CT) examinations, named WAZA-ARI, is being developed to accurately assess radiation doses to patients in Japan. For dose calculations in WAZA-ARI, organ doses were numerically analyzed using average adult Japanese male (JM) and female (JF) phantoms with the Particle and Heavy Ion Transport code System (PHITS). Experimental studies clarified the photon energy distribution of emitted photons and dose profiles on the table for some multi-detector row CT (MDCT) devices. Numerical analyses using a source model in PHITS could specifically take into account emissions of x rays from the tube to the table with attenuation of photons through a beam-shaping filter for each MDCT device based on the experiment results. The source model was validated by measuring the CT dose index (CTDI). Numerical analyses with PHITS revealed a concordance of organ doses with body sizes of the JM and JF phantoms. The organ doses in the JM phantoms were compared with data obtained using previously developed systems. In addition, the dose calculations in WAZA-ARI were verified with previously reported results by realistic NUBAS phantoms and radiation dose measurement using a physical Japanese model (THRA1 phantom). The results imply that numerical analyses using the Japanese phantoms and specified source models can give reasonable estimates of dose for MDCT devices for typical Japanese adults.

Cytogenetic analysis of radiation-induced leukemia in Trp53-deficient C3H/He mice.

C3H/He mice develop acute myeloid leukemia (AML) after whole-body irradiation, but the strain becomes highly susceptible to stem cell leukemia (SCL) when a null mutation is introduced into the Trp53 gene. To examine the etiology of SCL and the influence of chromosomal instability on leukemogenesis, 12 SCLs and two AMLs arising from Trp53-deficient C3H/He mice were investigated cytogenetically. Each SCL demonstrated cell-to-cell variation in the number and structural integrity of their chromosomes, indicating chromosomal instability. Typical deletion of chromosome 2 was observed in the two AML cases, while most SCL cells did not display this aberration. Deletions and rearrangements of chromosome 11 were noticeable in SCLs from Trp53 heterozygotes but not in AMLs. Analysis of loss of heterozygosity revealed that aberrations involving chromosome 11 in SCLs resulted in loss of the wild-type Trp53 allele. These results suggest that loss of Trp53 function triggers the tumorigenic process leading toward SCL through the induction of chromosomal instability, and that SCL and AML are distinct varieties of leukemia.

Fukushima Daiichi Nuclear Power Plant accident: facts, environmental contamination, possible biological effects, and countermeasures.

On March 11, 2011, an earthquake led to major problems at the Fukushima Daiichi Nuclear Power Plant. A 14-m high tsunami triggered by the earthquake disabled all AC power to Units 1, 2, and 3 of the Power Plant, and carried off fuel tanks for emergency diesel generators. Despite many efforts, cooling systems did not work and hydrogen explosions damaged the facilities, releasing a large amount of radioactive material into the environment. In this review, we describe the environmental impact of the nuclear accident, and the fundamental biological effects, acute and late, of the radiation. Possible medical countermeasures to radiation exposure are also discussed.

Radiation-induced bystander effects induce radioadaptive response by low-dose radiation.

When normal human fibroblast cells (MRC-5) received a priming irradiation of 3-20 mGy 4 h prior to irradiation with 1000 mGy, the number of DNA double-stranded breaks (DSBs) decreased significantly to 18.2-18.7 per cell compared with 21 per cell when there was no priming irradiation. This result indicates that a priming irradiation of 3-20 mGy induces a radioadaptive response in MRC-5. The authors' previous study had indicated that DSBs induced by ≤ 20 mGy are due to a radiation-induced bystander effect. These findings suggest that radiation-induced bystander effects might contribute to induction of the radioadaptive response. To test this hypothesis, MRC-5 were suspended in lindane, an inhibitor of radiation-induced bystander effects, which was added to the medium for the priming irradiation of 3-20 mGy. Lindane inhibited the protective effect of priming irradiation on DSBs caused by subsequent irradiation with 1000 mGy. Thus, radiation-induced bystander effects may play a role in radioadaptive responses.

Persistence of DNA double-strand breaks in normal human cells induced by radiation-induced bystander effect.

Our previous study suggested that the DNA double-strand breaks (DSBs) induced by very low X-ray doses are largely due to bystander effects. The aim of this study was to verify whether DSBs created by radiation-induced bystander effects are likely to be repaired. We examined the generation of DSBs in cells by enumeration of phosphorylated ataxia telangiectasia mutated (ATM) foci, which are correlated with DSB repair, in normal human fibroblast cells (MRC-5) after X irradiation at doses ranging from 1 to 1000 mGy. At 24 h after irradiation, 100% (1.2 mGy), 58% (20 mGy), 12% (200 mGy) and 8.5% (1000 mGy) of the initial number of phosphorylated ATM foci were detected. The number of phosphorylated ATM foci in MRC-5 cells treated with lindane, an inhibitor of radiation-induced bystander effects, prior to X irradiation was assessed; phosphorylated ATM foci were not observed at 5 h (20 mGy) or 24 h (200 mGy) postirradiation. We also counted the number of phosphorylated ATM foci in MRC-5 cells cocultured with MRC-5 cells irradiated with 20 mGy. After 48 h of coculture, 81% of the initial numbers of phosphorylated ATM foci remained. These findings suggest that DSBs induced by the radiation-induced bystander effect persist for long periods, whereas DSBs induced by direct radiation effects are repaired relatively quickly.

WAZA-ARI: computational dosimetry system for X-ray CT examinations. I. Radiation transport calculation for organ and tissue doses evaluation using JM phantom.

A web system of WAZA-ARI is being developed to assess radiation dose to a patient in a computed tomography examination. WAZA-ARI uses one of organ dose data sets corresponding to the options selected by a user to describe examination conditions. The organ dose data have been derived by the Particle and Heavy Ion Transport code system, combined with Japanese male (JM) phantom. The configuration of JM phantom is adjusted to the averaged JM adult. In addition, a new phantom is introduced by removing arms from JM phantom to take into account for dose calculations in torso examinations. Some of the organ doses by JM phantom without arms are compared with results obtained by using a MIRD-type phantom, which was applied in some previous dosimetry systems.

WAZA-ARI: computational dosimetry system for X-ray CT examinations II: development of web-based system.

A web-based dose computation system, WAZA-ARI, is being developed for patients undergoing X-ray CT examinations. The system is implemented in Java on a Linux server running Apache Tomcat. Users choose scanning options and input parameters via a web browser over the Internet. Dose coefficients, which were calculated in a Japanese adult male phantom (JM phantom) are called upon user request and are summed over the scan range specified by the user to estimate a normalised dose. Tissue doses are finally computed based on the radiographic exposure (mA s) and the pitch factor. While dose coefficients are currently available only for limited CT scanner models, the system has achieved a high degree of flexibility and scalability without the use of commercial software.

Nationwide survey on pediatric CT among children of public health and school nurses to examine a possibility for a follow-up study on radiation effects.

A nationwide survey was conducted in Japan on paediatric CT among children of public health and school nurses to examine a possibility for a follow-up study on radiation effects. A survey questionnaire was sent out to 3173 public primary and junior high schools and 317 public health centres during October to December in 2009. According to the collected responses, 410 (16.2 %) children received the CT scans and the total number of CT scans was 585. Most of respondents expressed a high interest in radiation health effects and an intent to participate in the epidemiological study that will follow-up the health conditions of children. This study provides information to discuss the feasibility of the epidemiological study on health effects in children who received CT scans.