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The Organisation for Economic Co-operation and Development (OECD) Adverse Outcome Pathway (AOP) Development Programme is being explored in the radiation field, as an overarching framework to identify and prioritize research needs that best support strengthening of radiation risk assessment and risk management strategies. To advance the use of AOPs, an international horizon-style exercise (HSE) was initiated through the Radiation/Chemical AOP Joint Topical Group (JTG) formed by the OECD Nuclear Energy Agency (NEA) High-Level Group on Low Dose Research (HLG-LDR) under the auspices of the Committee on Radiological Protection and Public Health (CRPPH). The intent of the HSE was to identify key research questions for consideration in AOP development that would help to reduce uncertainties in estimating the health risks following exposures to low dose and low dose-rate ionizing radiation. The HSE was conducted in several phases involving the solicitation of relevant questions, a collaborative review of open-ended candidate questions and an elimination exercise that led to the selection of 25 highest priority questions for the stated purpose. These questions were further ranked by over 100 respondents through an international survey. This final set of questions was judged to provide insights into how the OECD's AOP approach can be put into practice to meet the needs of hazard and risk assessors, regulators, and researchers. This paper examines the 25 priority questions in the context of hazard/risk assessment framework for ionizing radiation. By addressing the 25 priority questions, it is anticipated that constructed AOPs will have a high level of specificity, making them valuable tools for simplifying and prioritizing complex biological processes for use in developing revised radiation hazard and risk assessment strategies. [ABSTRACT FROM AUTHOR]

The risk of brain exposure to ionizing radiation increases gradually due to the extensive application of nuclear technology in medical, industrial, and aerospace fields. Radiation-induced brain injury (RBI) is highly likely to cause a wide range of neurological complications, including schizophrenia, Alzheimer's disease (AD), depression. Ginkgolide B (GB) is one of the effective active components extracted from ginkgo biloba leaves, exerts protective effects on CNS, which is involved in the regulation of the Hippo signaling pathway. MST1, as one of the core kinases of the Hippo pathway, participated in regulating cell proliferation, differentiation, and apoptosis. However, it remains unclear whether GB attenuates radiation brain injury (RBI) and whether the radioprotective effect of GB refers to MST1 signaling. Hence, our study aimed to explore the radiation protection effect and the potential mechanism of GB. C57BL/6 mice were stimulated with an X-ray (20 Gy) to establish an RBI model. Then, morris water maze test (MWM) and step-down passive avoidance test (SDPAT) were used to assess the learning and memory function of mice. The open field test (OFT), tail suspension test (TST), and forced swimming test (FST) were used to assess changes in locomotor activity and hopelessness. Besides, X-ray-stimulated SH-SY5Y cells were used to verify the radioprotective effect of GB. Immunofluorescence double staining, Dihydroethidium (DHE), western blot, and flow cytometry were used to explore the role of DCC/MST1 signaling in RBI. In this study, X-ray-treated mice exhibited cognitive impairment and depression-like behavior, which was ameliorated by GB treatment. GB also reduced the ROS production and the number of TUNEL-positive cells in the hippocampus. Moreover, GB increased the protein levels of p-AKT and Bcl2, while decreased the protein levels of MST1, p-p38, p-JNK, cleaved-caspase-3 and Bax both in vivo and in vitro. Additionally, exogenous Netrin-1 alleviated X-ray-induced ROS production and apoptosis, whereas knockout of Netrin-1 receptor DCC abolished the protective effect of GB. Oxidative stress and MST1-mediated neuronal apoptosis participated in radiation-induced cognitive impairment and depression-like behaviors, and modulation of DCC by GB was an effective intervention against RBI. [ABSTRACT FROM AUTHOR]

Abstract Purpose Materials and Methods Results and Conclusions Over the last decade or so, ethical and societal aspects of radiological protection have received increasing attention. This is also reflected in the publications of the International Commission on Radiological Protection (ICRP). The current paper aims at identifying relevant ethical and societal topics which should receive attention in the context of radiological protection for offspring and next generations.We present a non-comprehensive review of the subject, based on presentation made at an ICRP workshop in Budapest in 2022. We first discuss the ethical values promoted by ICRP, and the application of these values in cases of (potential) pre-conceptual and prenatal radiation exposures. We then consider experience gained after the Fukushima accident indicating particular societal concerns about the health effects of such exposures.Beneficence/non-maleficence, prudence, justice and dignity, the “core values” of the system of radiological protection have special roles to play when heritable and/or in utero effects are to be considered. Prudence, in particular, must be taken account of in view of the fact that solid scientific data in humans are largely lacking in this area, and it is necessary to rely on insights from animal experiments as well as theoretical considerations. As regards societal considerations, the perception of risk among (potentially) affected populations needs to be taken seriously. Accountability, transparency, and inclusivity, the “procedural values” promoted by ICRP for the practical implementation of the system of radiological protection play a central role in overcoming skepticism and creating trust. Stakeholder involvement should emphasize cooperation and dialogue, which allows for the joint evaluation of an exposure situation by experts and affected people. [ABSTRACT FROM AUTHOR]

The current paper is aimed to discuss the principles and criteria for health protection to radiofrequency electromagnetic field (RF EMF) considering both thermal and non-thermal mechanisms to evaluate the reasonable level for the limits relevant to control the level of RF EMF for the general public in the living environment. The study combines the conclusions of analyses published in recent reviews on RF EMF effects and the data from RF EMF measurements in different countries to select the possible criteria and to derive proposals for the health protection limits on the level of RF EMF following the ALARA principle – as low as reasonably achievable. Consideration of not only energetic but also coherent qualities of RF EMF leads to two different models for determining the impact of non-ionizing radiation on human health. The thermal model, based on absorption of electromagnetic energy, has a threshold limiting the heating of tissues. The non-thermal model, based on the ability of coherent electric fields to introduce biological effects at constant temperature, has no threshold. Therefore, the impact of RF EMF on human health cannot be excluded but can be minimized by limiting the level of the radiation. The limits can be selected based on indirect criteria. The minimal level of RF EMF that has caused a biological effect is about 2 V/m. The level of long-term broadcast radiation is 6 V/m and the people can be assumed to be adapted to that level without observable health problems. The level of RF EMF measured during last years does not exceed 5 V/m and the level is decreasing with newer generations of telecommunication technology. Limiting the level of RF EMF to the peak value of 6 V/m hopefully reduces the health risk to a minimal level people are adapted to and does not restrict the further development of telecommunication technology. [ABSTRACT FROM AUTHOR]

Ionizing radiation (IR) is widely applied in radiotherapy for the treatment of over 50% of cancer patients. IR is also intensively used in medical diagnostics on a daily basis in imaging. Moreover, recent geopolitical events have re-ignited the real threat of the use of nuclear weapons. Medical radiation countermeasures represent one of the effective protection strategies against the effects of IR. The aim of this review was to summarize the most commonly used strategies and procedures in the development of radiation countermeasures and to evaluate the current state of their research, with a focus on those in the clinical trial phase. Clinical trials for this review were selected in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. The search was performed in the clinicaltrials.gov database as of May 2022. Our search returned 263 studies, which were screened and of which 25 were included in the review. 10 of these studies had been completed, 3 with promising results: KMRC011 increased G-CSF, IL-6, and neutrophil counts suggesting potential for the treatment of hematopoietic acute radiation syndrome (H-ARS); GC4419 reduced the number of patients with severe oral mucositis and its duration; the combination of enoxaparin, pentoxifylline, and ursodeoxycholic acid reduced the incidence of focal radiation-induced liver injury. The agents discovered so far show significant side effects or low efficacy, and hence most of the tested agents terminate in the early stages of development. In addition, the low profitability of this type of drug demotivates the private sector to invest in such research. To overcome this problem, there is a need to involve more public resources in funding. Among the technological opportunities, a deeper use of in silico approaches seems to be prospective. [ABSTRACT FROM AUTHOR]

Purpose: The assumption that traversal of the cell nucleus by ionizing radiation is a prerequisite to induce genetic damage, or other important biological responses, has been challenged by studies showing that oxidative alterations extend beyond the irradiated cells and occur also in neighboring bystander cells. Cells and tissues outside the radiation field experience significant biochemical and phenotypic changes that are often similar to those observed in the irradiated cells and tissues. With relevance to the assessment of long-term health risks of occupational, environmental and clinical exposures, measurable genetic, epigenetic, and metabolic changes have been also detected in the progeny of bystander cells. How the oxidative damage spreads from the irradiated cells to their neighboring bystander cells has been under intense investigation. Following a brief summary of the trends in radiobiology leading to this paradigm shift in the field, we review key findings of bystander effects induced by low and high doses of various types of radiation that differ in their biophysical characteristics. While notable mechanistic insights continue to emerge, here the focus is on the many means of intercellular communication that mediate these effects, namely junctional channels, secreted molecules and extracellular vesicles, and immune pathways. Conclusions: The insights gained by studying radiation bystander effects are leading to a basic understanding of the intercellular communications that occur under mild and severe oxidative stress in both normal and cancerous tissues. Understanding the mechanisms underlying these communications will likely contribute to reducing the uncertainty of predicting adverse health effects following exposure to low dose/low fluence ionizing radiation, guide novel interventions that mitigate adverse out-of-field effects, and contribute to better outcomes of radiotherapeutic treatments of cancer. In this review, we highlight novel routes of intercellular communication for investigation, and raise the rationale for reconsidering classification of bystander responses, abscopal effects, and expression of genomic instability as non-targeted effects of radiation. [ABSTRACT FROM AUTHOR]

Cataract (opacification of the ocular lens) is a typical tissue reaction (deterministic effect) following ionizing radiation exposure, for which prevention dose limits have been recommended in the radiation protection system. Manifestations of radiation cataracts can vary among individuals, but such potential individual responses remain uncharacterized. Here we review relevant literature and discuss implications for radiation protection. This review assesses evidence for significant modification of radiation-induced cataractogenesis by age at exposure, sex and genetic factors based on current scientific literature. In addition to obvious physical factors (e.g. dose, dose rate, radiation quality, irradiation volume), potential factors modifying individual responses for radiation cataracts include sex, age and genetics, with comorbidity and coexposures also having important roles. There are indications and preliminary data identifying such potential modifiers of radiation cataract incidence or risk, although no firm conclusions can yet be drawn. Further studies and a consensus on the evidence are needed to gain deeper insights into factors determining individual responses regarding radiation cataracts and the implications for radiation protection. [ABSTRACT FROM AUTHOR]

The Adverse Outcome Pathway (AOP) framework, a systematic tool that can link available mechanistic data with phenotypic outcomes of relevance to regulatory decision-making, is being explored in areas related to radiation risk assessment. To examine the challenges including the use of AOPs to support the radiation protection community, an international horizon-style exercise was initiated through the Organisation for Economic Co-operation and Development Nuclear Energy Agency High-Level Group on Low Dose Research Radiation/Chemical AOP Joint Topical Group. The objective of the HSE was to facilitate the collection of ideas from a range of experts, to short-list a set of priority research questions that could, if answered, improve the description of the radiation dose-response relationship for low dose/dose-rate exposures, as well as reduce uncertainties in estimating the risk of developing adverse health outcomes following such exposures. The HSE was guided by an international steering committee of radiation risk experts. In the first phase, research questions were solicited on areas that can be supported by the AOP framework, or challenges on the use of AOPs in radiation risk assessment. In the second phase, questions received were refined and sorted by the SC using a best-worst scaling method. During a virtual 3-day workshop, the list of questions was further narrowed. In the third phase, an international survey of the broader radiation protection community led to an orderly ranking of the top questions. Of the 271 questions solicited, 254 were accepted and categorized into 9 themes. These were further refined to the top 25 prioritized questions. Among these, the higher ranked questions will be considered as 'important' to drive future initiatives in the low dose radiation protection community. These included questions on the ability of AOPs to delineate responses across different levels of biological organization, and how AOPs could be applied to address research questions on radiation quality, doses or dose-rates, exposure time patterns and deliveries, and uncertainties in low dose/dose-rate effects. A better understanding of these concepts is required to support the use of the AOP framework in radiation risk assessment. Through dissemination of these results and considerations on next steps, the JTG will address select priority questions to advance the development and use of AOPs in the radiation protection community. The major themes observed will be discussed in the context of their relevance to areas of research that support the system of radiation protection. [ABSTRACT FROM AUTHOR]

The concept of the adverse outcome pathway (AOP) has recently gained significant attention as to its potential for incorporation of mechanistic biological information into the assessment of adverse health outcomes following ionizing radiation (IR) exposure. This work is an account of the activities of an international expert group formed specifically to develop an AOP for IR-induced leukemia. Group discussions were held during dedicated sessions at the international AOP workshop jointly organized by the MELODI (Multidisciplinary European Low Dose Initiative) and the ALLIANCE (European Radioecology Alliance) associations to consolidate knowledge into a number of biological key events causally linked by key event relationships and connecting a molecular initiating event with the adverse outcome. Further knowledge review to generate a weight of evidence support for the Key Event Relationships (KERs) was undertaken using a systematic review approach. An AOP for IR-induced acute myeloid leukemia was proposed and submitted for review to the OECD-curated AOP-wiki (aopwiki.org). The systematic review identified over 500 studies that link IR, as a stressor, to leukemia, as an adverse outcome. Knowledge gap identification, although requiring a substantial effort via systematic review of literature, appears to be one of the major added values of the AOP concept. Further work, both within this leukemia AOP working group and other similar working groups, is warranted and is anticipated to produce highly demanded products for the radiation protection research community. [ABSTRACT FROM AUTHOR]

Studies on human health and ecological effects of ionizing radiation are rapidly evolving as innovative technologies arise and the body of scientific knowledge grows. Structuring this information could effectively support the development of decision making tools and health risk models to complement current system of radiation protection. To this end, the adverse outcome pathway (AOP) approach is being explored as a means to consolidate the most relevant research to identify causation between exposure to a chemical or non-chemical stressor and disease or adverse effect progression. This tool is particularly important for low dose and low dose rate radiation exposures because of the latency and uncertainties in the biological responses at these exposure levels. To progress this aspect, it is essential to build a community of developers, facilitators, risk assessors (in the private sector and in government), policy-makers, and regulators who understand the strengths and weaknesses of, and how to appropriately utilize AOPs for consolidating our knowledge on the impact of low dose ionizing radiation. Through co-ordination with the Organisation of Economic Co-operation and Development (OECD) Nuclear Energy Agency (NEA) High-Level Group on Low-Dose Research (HLG-LDR) and OECD's AOP Programme, initiatives are under way to demonstrate this approach in radiation research and regulation. Among these, a robust communications strategy and stakeholder engagement will be essential. It will help establish best practices for AOPs in institutional project development and aid in dissemination for more efficient and timely uptake and use of AOPs. In this regard, on June 1, 2021, the Radiation and Chemical (Rad/Chem) AOP Joint Topical Group was formed as part of the initiative from the NEA's HLG-LDR. The topical group will work to develop a communication and engagement strategy to define the target audiences, establish the clear messages and identify the delivery and engagement platforms. The incorporation of the best science and better decision making should motive the radiation protection community to develop, refine and use AOPs, recognizing that their incorporation into radiation health risk assessments is critical for public health and environmental protection in the 21st century. [ABSTRACT FROM AUTHOR]

The purpose of toxicology is to protect human health and the environment. To support this, the Organisation for Economic Co-operation and Development (OECD), operating via its Extended Advisory Group for Molecular Screening and Toxicogenomics (EAGMST), has been developing the Adverse Outcome Pathway (AOP) approach to consolidate evidence for chemical toxicity spanning multiple levels of biological organization. The knowledge transcribed into AOPs provides a structured framework to transparently organize data, examine the weight of evidence of the AOP, and identify causal relationships between exposure to stressors and adverse effects of regulatory relevance. The AOP framework has undergone substantial maturation in the field of hazard characterization of chemicals over the last decade, and has also recently gained attention from the radiation community as a means to advance the mechanistic understanding of human and ecological health effects from exposure to ionizing radiation at low dose and low dose-rates. To fully exploit the value of such approaches for facilitating risk assessment and management in the field of radiation protection, solicitation of experiences and active cooperation between chemical and radiation communities are needed. As a result, the Radiation and Chemical (Rad/Chem) AOP joint topical group was formed on June 1, 2021 as part of the initiative from the High Level Group on Low Dose Research (HLG-LDR). HLG-LDR is overseen by the OECD Nuclear Energy Agency (NEA) Committee on Radiation Protection and Public Health (CRPPH). The main aims of the joint AOP topical group are to advance the use of AOPs in radiation research and foster broader implementation of AOPs into hazard and risk assessment. With global representation, it serves as a forum to discuss, identify and develop joint initiatives that support research and take on regulatory challenges. The Rad/Chem AOP joint topical group will specifically engage, promote, and implement the use of the AOP framework to: (a) organize and evaluate mechanistic knowledge relevant to the protection of human and ecosystem health from radiation; (b) identify data gaps and research needs pertinent to expanding knowledge of low dose and low dose-rate radiation effects; and (c) demonstrate utility to support risk assessment by developing radiation-relevant case studies. It is envisioned that the Rad/Chem AOP joint topical group will actively liaise with the OECD EAGMST AOP developmental program to collectively advance areas of common interest and, specifically, provide recommendations for harmonization of the AOP framework to accommodate non-chemical stressors, such as radiation. [ABSTRACT FROM AUTHOR]

Radium is the most common source of alpha radiation exposure to humans and non-human species in the environment but the dosimetry is complicated by the decay chain which involves gamma exposure due to radon daughters. This paper seeks to determine the separate contributions of alpha and gamma doses to the total dose and total direct and non-targeted effect in a fish and a human cell line. This study aimed to isolate the effect of alpha particles following exposure to low doses of radium in cells, and their progeny which received no further exposure. This was initially done by comparing the survival values of a human keratinocyte cell line (HaCaT) and an embryonic Chinook salmon cell line (CHSE-214) exposed to gamma radiation, from survival of the same cell lines exposed to mixed alpha and gamma radiation through exposure to Ra-226 and its decay products. A Monte Carlo simulation was later performed to determine the contributions of radium decay products including radon daughters. The human cell line showed increased radioresistance when exposed to low doses of alpha particles. In contrast the fish cell line, which demonstrated radioresistance to low dose gamma radiation, showed increased lethality when exposed to low doses of alpha particles. Significant and complex levels of non-targeted effects were induced in progeny of irradiated cells. The simulation showed that gamma and beta decay products did not contribute significant dose and the highest beta dose was below the threshold for inducing non-targeted effects. The results confirm the need to consider the dose-response relationship when developing radiation weighting factors for low dose exposures, as well as the need to be aware of possible cell line and species differences. [ABSTRACT FROM AUTHOR]

Fish cell lines, collectively referred to as the fish invitrome, are useful diagnostic tools to study radiation impacts on aquatic health and elucidate radiation mechanisms in fish. This paper will highlight the advantages, discuss the challenges, and propose possible future directions for uses of the fish invitrome in the field of environmental radiobiology. The fish invitrome contains at least 714 fish cell lines. However, only a few of these cell lines have been used to study radiation biology in fish and they represent only 10 fish species. The fish invitrome is clearly not yet explored for its full potential in radiation biology. Evidence suggests that they are useful and, in some cases, irreplaceable in making underlying theories and fundamental concepts in radiation responses in fish. The debate of whether environmental radiation is harmful, presents risks, has no effect on health, or is beneficial is on-going and is one that fish cell lines can help address in a time-effective fashion. Any information obtained with fish cell lines is useful in the framework of environment radiation risk assessments. Radiation threats to aquatic health will continue due to the very likely rise of nuclear energy and medicine in the future. The fish invitrome, in theory, lives forever and can meet new challenges at any given time to provide diagnostic risk analyses pertaining to aquatic health and environmental radiation protection. [ABSTRACT FROM AUTHOR]

The objective of this paper is to present the results of discussions at a workshop held as part of the International Congress of Radiation Research (Environmental Health stream) in Manchester UK, 2019. The main objective of the workshop was to provide a platform for radioecologists to engage with radiobiologists to address major questions around developing an Ecosystem approach in radioecology and radiation protection of the environment. The aim was to establish a critical framework to guide research that would permit integration of a pan-ecosystem approach into radiation protection guidelines and regulation for the environment. The conclusions were that the interaction between radioecologists and radiobiologists is useful in particular in addressing field versus laboratory issues where there are issues and challenges in designing good field experiments and a need to cross validate field data against laboratory data and vice versa. Other main conclusions were that there is a need to appreciate wider issues in ecology to design good approaches for an ecosystems approach in radioecology and that with the capture of 'Big Data', novel tools such as machine learning can now be applied to help with the complex issues involved in developing an ecosystem approach. [ABSTRACT FROM AUTHOR]

This commentary explores the challenges in radiation safety that derives from the inherent complexity of social–ecological systems. The framework needed to address the challenges acknowledges the characteristics of wicked problems in this era of postnormal science. My objective for this piece is to summarize relevant characteristics of social–ecological systems that underscore the importance, even the necessity, of adopting a holistic approach to radiation safety. This work builds on several publications that have come out of the ecosystems approach working group of the International Union of Radioecology. The nature of wicked problems is that they require meaningful engagement among diverse groups of affected stakeholders so that negotiated consensus regarding assessment and management for radiation safety can be achieved. I conclude by stating that this approach is complementary to the reference animal and plant approach, that it is consistent with the views for postnormal science, and it conforms with the United Nations Sustainable Development Goals (SDGS) that were adopted in 2015. [ABSTRACT FROM AUTHOR]

Crucially, some of the few studies that used an ecosystem level approach by analyzing leaf litter decomposition (an ecosystem function) also reported divergent conclusions (Mousseau et al. [35]; Bonzom et al. [2]), strengthening the need to better unravel ecosystem level impacts. But the same low doses would be capable of triggering perturbation at multispecies ecosystem level, especially when the ecosystem is poorly resilient (as would result from permanent long-term exposure to low doses of contaminants). Keywords: Ecosystems; environment protection; ecological risk assessment; radiation EN Ecosystems environment protection ecological risk assessment radiation 999 1007 9 06/13/22 20220601 NES 220601 1. Tackling assessment of ecosystem condition in relation to stressors requires to integrate toxicological knowledge together with ecosystem understanding, such as to be able to derive how ecosystem structure and functions can be best protected from degradation triggered by stressors. [Extracted from the article]

Advanced angiographic procedures in interventional radiology are becoming more important and are more frequently used, especially in the treatment of several acute life-threatening diseases like stroke or aortic injury. In recent years, technical advancement has led to a broader spectrum of interventions and complex procedures with longer fluoroscopy times. This involves the risk of higher dose exposures, which, in rare cases, may cause deterministic radiation effects, e.g. erythema in patients undergoing angiographic procedures. Against this background, these procedures recently also became subject to national and international regulations regarding radiation protection. At the same time, individual risk assessment of possible stochastic radiation effects for each patient must be weighed up against the anticipated benefits of the therapy itself. Harmful effects of the administered dose are not limited to the patient but can also affect the radiologist and the medical staff. In particular, the development of cataracts in interventionalists is a rising matter of concern. Furthermore, long-term effects of repeated and prolonged x-ray exposure have long been neglected by radiologists but have come into focus in the past years. With all this in mind, this review discusses different efforts to reduce radiation exposition levels for patients and medical staff by means of technical, personal as well as organizational measures. [ABSTRACT FROM AUTHOR]

This review focuses on recent research in understanding the different aspects of what society should expect from a radiological attack. Although some scenarios of a radiologic event can be impossible to be prepared for, the effort put toward educating and better preparing for these types of events can help minimize some of the issues. The different areas discussed in this review include radioisotopes of concern, detection of radiation dose, biological effects of ionizing radiation exposures, low dose effects, targeted and non-targeted effects (NTE), psychological effects, mitigations, with a brief mention of other considerations such as medical preparedness, communication, policy implications and ethical issues. This review also discusses solutions to rectify the issues faced at hand that may come up in the event of a radiologic terrorist attack. A review of recent work in the area shows that a multi-layered and interdisciplinary approach is needed to prepare for a radiological terrorist attack. As well as medical preparedness, the approach needs to include sociological and psychological planning as well as an understanding of ethical issues. Since the likely 'dirty bomb' scenarios may involve low dose exposures to high numbers of people, a much better theoretical and practical understanding of low dose radiobiology and the development of robust low dose exposure biomarkers is needed as part of an integrated plan. [ABSTRACT FROM AUTHOR]

This paper reviews the history of the radium dial workers in the United States, summarizes the scientific progress made since the last evaluation in the early 1990s, and discusses current progress in updating the epidemiologic cohort and applying new dosimetric models for radiation risk assessment. The discoveries of radiation and radioactivity led quickly to medical and commercial applications at the turn of the 20th century, including the development of radioluminescent paint, made by combining radium with phosphorescent material and adhesive. Workers involved with the painting of dials and instruments included painters, handlers, ancillary workers, and chemists who fabricated the paint. Dial painters were primarily women and, prior to the mid to late 1920s, would use their lips to give the brush a fine point, resulting in high intakes of radium. The tragic experience of the dial painters had a significant impact on industrial safety standards, including protection measures taken during the Manhattan Project. The dial workers study has formed the basis for radiation protection standards for intakes of radionuclides by workers and the public. The mortality experience of 3,276 radium dial painters and handlers employed between 1913 and 1949 is being determined through 2019. The last epidemiologic follow-up was 30 years ago when most of these workers were still alive. Nearly 65% were born before 1920, 37.5% were teenagers when first hired, and nearly 50% were hired before 1930 when the habit of placing brushes in mouths essentially stopped. Comprehensive dose reconstruction techniques are being applied to estimate organ doses for each worker related to the intake of 226Ra, 228Ra, and associated photon exposures. Time dependent dose-response analyses will estimate lifetime risks for specific causes of death. The study of radium dial workers is part of the Million Person Study of low-dose health effects that is designed to evaluate radiation risks among healthy American workers and veterans. Despite being one of the most important and influential radiation effects studies ever conducted, shifting programmatic responsibilities and declining funding led to the termination of the radium program of studies in the early 1990s. Renewed interest and opportunity have arisen. With scientific progress made in dosimetric methodology and models, the ability to perform a study over the entire life span, and the potential applicability to other scenarios such as medicine, environmental contamination and space exploration, the radium dial workers have once again come to the forefront. [ABSTRACT FROM AUTHOR]

The study of low dose and low-dose rate exposure is of immeasurable value in understanding the possible range of health effects from prolonged exposures to radiation. The Million Person Study (MPS) of low-dose health effects was designed to evaluate radiation risks among healthy American workers and veterans who are more representative of today's populations than are the Japanese atomic bomb survivors exposed briefly to high-dose radiation in 1945. A million persons were needed for statistical reasons to evaluate low-dose and dose-rate effects, rare cancers, intakes of radioactive elements, and differences in risks between women and men. The MPS consists of five categories of workers and veterans exposed to radiation from 1939 to the present. The U.S. Department of Energy (DOE) Health and Mortality study began over 40 years ago and is the source of ∼360,000 workers. Over 25 years ago, the National Cancer Institute (NCI) collaborated with the U.S. Nuclear Regulatory Commission (NRC) to effectively create a cohort of nuclear power plant workers (∼150,000) and industrial radiographers (∼130,000). For over 30 years, the Department of Defense (DoD) collected data on aboveground nuclear weapons test participants (∼115,000). At the request of NCI in 1978, Landauer, Inc., (Glenwood, IL) saved their dosimetry databases which became the source of a cohort of ∼250,000 medical and other workers. Overall, 29 individual cohorts comprise the MPS of which 21 have been or are under active study (∼810,000 persons). The remaining eight cohorts (∼190,000 persons) will be studied as resources become available. The MPS is a national effort with critical support from the NRC, DOE, National Aeronautics and Space Administration (NASA), DoD, NCI, the Centers for Disease Control and Prevention (CDC), the Environmental Protection Agency (EPA), Landauer, Inc., and national laboratories. The MPS is designed to address the major unanswered question in radiation risk understanding: What is the level of health effects when exposure is gradual over time and not delivered briefly. The MPS will provide scientific understandings of prolonged exposure which will improve guidelines to protect workers and the public; improve compensation schemes for workers, veterans and the public; provide guidance for policy and decision makers; and provide evidence for or against the continued use of the linear nonthreshold dose-response model in radiation protection. [ABSTRACT FROM AUTHOR]

The National Council on Radiation Protection and Measurements (NCRP) is coordinating an expansive epidemiologic effort entitled the Million Person Study of Low-Dose Radiation Health Effects (MPS). Medical workers constitute the largest occupational radiation-exposed group whose doses are typically received gradually over time. A unique opportunity exists to establish an Institutional Review Board/Privacy Board (IRB/PB) approved, retrospective feasibility sub-cohort of diseased Memorial Sloan Kettering Cancer Center (MSK) medical radiation workers to reconstruct occupational/work history, estimate organ-specific radiation absorbed doses, and review existing publicly available records for mortality from cancer (including leukemia) and other diseases. Special emphasis will be placed on dose reconstruction approaches as a means to provide valid organ dose estimates that are as accurate and precise as possible based on the available data, and to allow proper evaluation of accompanying uncertainties. Such a study that includes validated dose measurements and information on radiation exposure conditions would significantly reduce dose uncertainties and provided greatly improved information on chronic low-dose risks. The feasibility sub-cohort will include deceased radiation workers from MSK who worked during the nearly seventy-year timeframe from 1946 through 2010 and were provided individual personal radiation dosimetry monitors. A feasibility assessment focused on obtaining records for about 25–30,000 workers, with over 124,000 annual doses, including personnel/work histories, specific dosimetry data, and appropriate information for epidemiologic mortality tracing will be conducted. MSK radiation dosimetry measurements have followed stringent protocols complying with strict worker protection standards in order to provide accurate dose information for radiation workers that include detailed records of work practices (including specific task exposure conditions, radiation type, energy, geometry, personal protective equipment usage, badge position, and missed doses), as well as recorded measurements. These dose measurements have been ascertained through a variety of techniques that have evolved over the years, from film badges to thermoluminescent dosimetry technology to optically stimulated luminescent methodologies. It is expected that individual total doses for the sub-cohort will have a broad range from <10 mSv to > =1000 mSv. MSK has pioneered the use of novel radiation diagnostic and therapeutic approaches over time (including initial work with x-rays, radium, and radon), with workplace safety in mind, resulting in a variety of radiation worker exposure scenarios. The results of this feasibility sub-cohort of deceased radiation workers, and associated lessons learned may potentially be applied to an expanded multicenter study of about 170,000 medical radiation worker component of the MPS. [ABSTRACT FROM AUTHOR]

Element-specific biokinetic models are used to reconstruct doses to systemic tissues from internal emitters. Typically, a systemic model for a radionuclide explicitly depicts only its dominant repositories. Remaining tissues and fluids are aggregated into a pool called Other tissue in which the radionuclide is assumed to be uniformly distributed. In the systemic biokinetic models used in radiation protection, the brain usually is addressed as an implicit mass fraction of Other tissue rather than an explicitly depicted repository. Due to increasing interest in radiation effects on the brain, efforts are underway to improve brain dosimetry for internal radiation sources. We assessed potential improvements in brain dosimetry for internal emitters by explicitly modeling brain kinetics rather than treating the brain as a mass fraction of Other tissue. We selected 10 elements for which brain kinetics can be modeled using published biokinetic data. Injection dose coefficients were calculated for a relatively long-lived radioisotope of each element using each of two versions of the ICRP's latest systemic biokinetic model for the element, the original version and a modified version differing only in the treatment of brain. If the ICRP model contained an explicit brain pool, the modified version depicted brain instead as a mass fraction of Other tissue. If the ICRP model included brain in Other tissue, the modified version included an explicit brain pool with kinetics based on best available brain-specific data. The result for a given radionuclide is expressed as a ratio A:B, where A and B are the dose coefficients based on the versions of the model with and without an explicit brain pool, respectively. The following ratios A:B were obtained for the 10 radionuclides addressed here: 241Am, 0.13; 207Bi, 0.57; 234U, 0.81; 239Pu, 0.96; 203Hg (vapor), 1.4; 134Cs, 1.5; 54Mn, 1.7; 210Po, 1.7; 226Ra, 1.9; 210Pb, 3.3. These ratios indicate that a dose estimate for brain based on a biokinetic model with brain implicitly contained in Other tissue may substantially underestimate or substantially overestimate a dose estimate that reflects best available brain-specific biokinetic data. Of course, the reliability of the latter estimate depends on the quality of the underlying biokinetic data. Where feasible, the brain should be depicted explicitly in biokinetic models used in epidemiological studies addressing adverse effects of ionizing radiation. [ABSTRACT FROM AUTHOR]

Scientific Committee 6–9 was established by the National Council on Radiation Protection and Measurements (NCRP), charged to provide guidance in the derivation of organ doses and their uncertainty, and produced a report, NCRP Report No. 178, Deriving Organ Doses and their Uncertainty for Epidemiologic Studies with a focus on the Million Person Study of Low-Dose Radiation Health Effects (MPS). This review summarizes the conclusions and recommendations of NCRP Report No. 178, with a concentration on and overview of the dosimetry and uncertainty approaches for the cohorts in the MPS, along with guidelines regarding the essential approaches used to estimate organ doses and their uncertainties (from external and internal sources) within the framework of an epidemiologic study. The success of the MPS is tied to the validity of the dose reconstruction approaches to provide realistic estimates of organ-specific radiation absorbed doses that are as accurate and precise as possible and to properly evaluate their accompanying uncertainties. The dosimetry aspects for the MPS are challenging in that they address diverse exposure scenarios for diverse occupational groups being studied over a period of up to 70 y. Specific dosimetric reconstruction issues differ among the varied exposed populations that are considered: atomic veterans, U.S. Department of Energy workers exposed to both penetrating radiation and intakes of radionuclides, nuclear power plant workers, medical radiation workers, and industrial radiographers. While a major source of radiation exposure to the study population comes from external gamma- or x-ray sources, for some of the study groups, there is also a meaningful component of radionuclide intakes that requires internal radiation dosimetry assessments. [ABSTRACT FROM AUTHOR]

Dr. Alice Stewart, 1906–2002, came from a medical background which included a strong commitment to social justice and equality. Her father became Professor of Medicine at Sheffield University and her mother was one of the first women to qualify as a doctor, and together they practiced in Hillsborough, near Sheffield. Having qualified as a doctor herself in 1932, Alice worked in London hospitals before moving to Oxford, where she became a pioneer in epidemiology. Early in her career, she showed that X-raying pregnant women was a cause of childhood leukemia. Her later work focused on the harmful effects of low-level radiation on nuclear industry workers, the role of background radiation and she went on to question the dose limits set for radiation protection. All her results were initially challenged, but subsequent studies have borne out her findings. Dr Alice Stewart's research was pioneering, fundamental and challenging, and is now widely accepted. [ABSTRACT FROM AUTHOR]

The aim of this brief personal, high level review is to consider the state of the art for biological dosimetry for radiation routine and emergency response, and the potential future progress in this fascinating and active field. Four areas in which biomarkers may contribute to scientific advancement through improved dose and exposure characterization, as well as potential contributions to personalized risk estimation, are considered: emergency dosimetry, molecular epidemiology, personalized medical dosimetry, and space travel. Ionizing radiation biodosimetry is an exciting field which will continue to benefit from active networking and collaboration with the wider fields of radiation research and radiation emergency response to ensure effective, joined up approaches to triage; radiation epidemiology to assess long term, low dose, radiation risk; radiation protection of workers, optimization and justification of radiation for diagnosis or treatment of patients in clinical uses, and protection of individuals traveling to space. Well established and newer biodosimetric techniques show promise for a number of future dosimetry or wider research application. PCC: Premature chromosome condensation. [ABSTRACT FROM AUTHOR]

As part of the special issue on 'Women in Science', this review offers a perspective on past and ongoing work in the field of normal (non-cancer) tissue radiation biology, highlighting the work of many of the leading contributors to this field of research. We discuss some of the hypotheses that have guided investigations, with a focus on some of the critical organs considered dose-limiting with respect to radiation therapy, and speculate on where the field needs to go in the future. The scope of work that makes up normal tissue radiation biology has and continues to play a pivotal role in the radiation sciences, ensuring the most effective application of radiation in imaging and therapy, as well as contributing to radiation protection efforts. However, despite the proven historical value of preclinical findings, recent decades have seen clinical practice move ahead with altered fractionation scheduling based on empirical observations, with little to no (or even negative) supporting scientific data. Given our current appreciation of the complexity of normal tissue radiation responses and their temporal variability, with tissue- and/or organ-specific mechanisms that include intra-, inter- and extracellular messaging, as well as contributions from systemic compartments, such as the immune system, the need to maintain a positive therapeutic ratio has never been more urgent. Importantly, mitigation and treatment strategies, whether for the clinic, emergency use following accidental or deliberate releases, or reducing occupational risk, will likely require multi-targeted approaches that involve both local and systemic intervention. From our personal perspective as five 'Women in Science', we would like to acknowledge and applaud the role that many female scientists have played in this field. We stand on the shoulders of those who have gone before, some of whom are fellow contributors to this special issue. [ABSTRACT FROM AUTHOR]

This extraordinary woman worked her professional way from a radiation protection engineer to become the successful principal investigator of a prestigious international European project for a new radiation therapy (ERC Synergy grant, HORIZON 2020). The evaluation of the submitted proposal was very positive. The panel proposed that it be funded. Elke tragically passed away a few days before this conclusion of the panel. The present account describes her gradual career development; it includes many episodes that Elke personally chronicled in her curriculum of 2017. An internet literature search was performed using Google Scholar and other sources to assist in the writing of this narrative review and account. In parallel to the development of the new Biomedical Beamline ID17 at the European Synchrotron Radiation Facility in Grenoble in the late nineties, Elke focused her interest and her personal and professional priorities on MRT, particularly on its clinical goals. She outlined her main objectives in several documents: (1) develop a new paradigm of cancer care by broadening the foundation for MRT. (2) Filling the gaps in basic biological knowledge about the mechanisms of MRT effects on normal and neoplastic tissues. (3) Broaden the preclinical level of evidence for the low normal organ toxicity of MRT versus standard X-ray irradiations; preclinical experiments involved the application of MRT to animal tumor patients, to animals of larger size than laboratory rodents, using larger radiation field sizes, and irradiating in a real-time scenario comparable to the one planned for human patients. (4) To foster the specific purpose of radiosurgical MRT of tumor patients at the ESRF that required development of new, specific state of the art modalities and tools for treatment planning, dosimetry, dose calculation, patient positioning and, of particular importance, redundant levels of patient safety. Just as she was about to take responsibility as principal investigator for a prestigious international European project on a new radiation therapy, death called Elke in. [ABSTRACT FROM AUTHOR]

As a biologist who, since the beginning of her involvement in science, has collaborated closely with physicists, I want to share my forty years of experience describing the events that introduced me to the world of charged particle radiation biology as well as that of low doses/dose rates, with related implications in medicine and radiation protection. The main features of my experience can be summarized in the development of an interdisciplinary culture and in the interest in technological advances for the study of biological responses to radiation in different scenarios, relevant for public health. Mine was a journey that began by chance, but which led me to a world that proved to be of great interest to me. With the current advances in science, the new generations of scientists have new opportunities that I wish them to face with the same interest and enthusiasm that I felt for such an interdisciplinary field as that of radiation biology. [ABSTRACT FROM AUTHOR]

The purpose of the study was to show the outstanding contribution of Elena Alexandrovna Timofeeva-Resovskaya (1898–1973) to the development of radiobiology. We reviewed the author's memoirs and materials from the personal archive, as well as literary and electronic sources. For the first time the autobiography of Elena A. Timofeeva-Resovskaya and the periods of her scientific activity were revealed. We demonstrated the primary role of Elena A. Timofeeva-Resovskaya in the research of aquatic ecosystems. The results of her research turned out to be important both for solving the problems of radioactive contamination of territories and for the development of modern radioecology. Throughout her life, she worked with her husband Nikolay V. Timofeev-Resovsky (1900–1981), a great scientist and prominent scientific enlightener. There was no purpose to describe the life of Timofeev-Resovskies family, full of exciting events, but it was not possible to avoid it. For young women in science, Elena A. Timofeeva-Resovskaya can provide an example of a successful scientific career even in turbulent times. [ABSTRACT FROM AUTHOR]

This special issue of the International Journal of Radiation Biology entitled "Adverse Outcome Pathways in Radiation Protection" is inspired by growing global interest in approaches for integrating information from radiation biology and epidemiology to improve scientific understanding of low dose radiation health risk assessment. Also explored is benchmark dose modeling as a means to identify a point of departure (POD) for adverse phenotypic effects using transcriptional dose-response data (Chauhan et al. [8]). However, before this goal is reached, some important questions need to be addressed as to how different types, doses and dose rates of radiation exposure can accurately inform AOP development and how AOPs can reflect the latency of adverse health outcomes in a simplified form. [Extracted from the article]

Plants can be sources of photoprotective/antigenotoxic compounds that prevent cellular mutations involved in skin cancer and aging by regulating UV-induced mutability. The study was aimed at investigating the sunscreen properties of plants growing in Colombia. Ultraviolet (UV) radiation-absorption capability of different plant extracts was examined. In vitro photoprotection efficacies were evaluated using in vitro indices such as sun protection factor (SPFin vitro) and critical wavelength (λc). Pearson correlation analysis was used to examine the relationship between SPFin vitro and complementary UVB- antigenotoxicity estimates (%GI) based on the SOS Chromotest database. The cytotoxicity in human fibroblasts was studied using the trypan blue exclusion assay. Major compounds of promising plant extracts were determined by gas chromatography coupled to mass spectrometry (GC/MS). We showed that plant extracts have sunscreen properties against UVB, whereas broad-spectrum radiation protection efficacy was poor. SPFin vitro and %GI were correlated (R = 0.71, p <.0001) for the plant extracts under study. Three extracts obtained from Achyrocline satureioides, Chromolaena pellia, and Lippia origanoides species resulted to possess high protection efficacy and relatively low cytotoxicity in human fibroblasts. These plant extracts contained major compounds such as α-pinene, trans-β-caryophyllene, γ-muurolene, γ-cadinene and caryophyllene oxide in A. Satureioides extract, trans-β-caryophyllene, caryophyllene oxide, squalene and α-amyrin in C. pellia extract, and p-cymene, carvacrol, trans-β-caryophyllene and pinocembrin in L. origanoides extract. Plants growing in Colombia contain compounds that can be useful for potential sunscreens. SPFin vitro and %GI estimates were correlated, but %GI estimates were more sensitive to detecting activity at lower plant extract concentrations. Our results supported the need to use DNA damage detection assays as a complement to photoprotection efficacy measurement. [ABSTRACT FROM AUTHOR]

Canadian Organization on Health Effects from Radiation Exposure (COHERE) is a government initiative to better understand biological and human health risks from ionizing radiation exposures relevant to occupational and environmental settings (<100 mGy, <6 mGy/h). It is currently a partnership between two federal agencies, Health Canada (HC) and the Canadian Nuclear Safety Commission (CNSC). COHERE's vision is to contribute knowledge to reduce scientific uncertainties from low dose and dose-rate exposures. COHERE will advance our understanding by bridging the knowledge gap between human health risks and linkages to molecular- and cellular-level responses to radiation. Research focuses on identifying sensitive, early, and key molecular events of relevance to risk assessment. The initiative will address questions of relevance to better apprize Canadians, including radiation workers and members of the public and Indigenous peoples, on health risks from low dose radiation exposure and inform radiation protection frameworks at a national and international level. Furthermore, it will support global efforts to conduct collaborative undertakings and better coordinate research. Here, we describe a historical overview of the research conducted, the strategic research agenda that outlines the scientific framework, stakeholders, opportunities to harmonize internationally, and how research outcomes will better inform communication of risk to Canadians. [ABSTRACT FROM AUTHOR]

Disease prevention and prediction have led to the generation of phenotypically based methods for deriving the limits of safety across toxicological disciplines. In the ionizing radiation field, human data has formed the basis of the linear-no-threshold (LNT) model for risk estimates. However, uncertainties around its accuracy at low doses and low dose-rates have led to passionate debates on its effectiveness to derive radiation risk estimates under these conditions. Concerns arise from the linear extrapolation of data from high doses to low doses, below 0.1 Gy where there is considerable variability in the scientific literature. Efforts to address these controversies have led to a mountain of mechanistic data to improve the understanding of molecular and cellular effects related to phenotypic changes. These data provide fragments of information that have yet to be combined and used effectively to improve modeling, reduce uncertainties, and update radiation protection approaches. This paper suggests a better consolidation of mechanistic research may serve to guide priority research and facilitate translation to risk assessment. An effective approach that may be implemented is the organization of data using the adverse outcome pathway (AOP) framework, a programme that has been launched by the Organization for Economic Cooperation and Development in the chemical toxicology field. The AOP concept has proved beneficial to human health and ecological toxicological fields, demonstrating possibilities for better linkages of mechanistic data to phenotypic effects. A similar approach may be beneficial to the field of radiation research. However, for this to work effectively, collaborative efforts are needed among the scientific communities in the area of AOP development and documentation. Studies will need to be evaluated, re-organized and integrated into AOPs. Here, details of the AOP approach and areas it could support in the radiation field are discussed. In addition, challenges are highlighted and steps to integration are outlined. Organizing studies in this manner will facilitate a better understanding of our current knowledge in the radiation field and help identify areas where more focused work can be undertaken. This will, in turn, allow for improved linkage of mechanistic data to human relevance and better support radiation risk assessments. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: The projected existence and magnitude of carcinogenic effects of ionizing radiation at low doses and low-dose rates is perhaps the most important issue in radiation protection today. Studies of childhood cancer and natural background radiation have the potential to throw direct light on this question, into a dose range below a few tens of mSv. This paper describes the studies that have been undertaken and their context, discusses some problems that arise and summarizes the present position. Conclusions: Many such studies have been undertaken, but most were too small to have a realistic chance of detecting the small effects expected from such low doses, based on risk projections from higher exposures. Case--control or cohort studies are to be preferred methodologically to ecological studies but can be prone to problems of registration/participation bias. Interview-based studies of the requisite size would be prohibitively expensive and would undoubtedly also run into problems of participation bias. Register-based studies can be very large and are free of participation bias. However, they need to estimate the radiation exposure of study subjects using models rather than individual measurements in the homes of those concerned. At present, no firm conclusions can be drawn from the studies that have been published to date. Further data and perhaps pooled studies offer a way forward. [ABSTRACT FROM AUTHOR]

Radiation exposure is an on going and serious threat in military and public health concern. There is an unmet need for effective preventative or mitigative treatments against radiation-induced injuries. The handful of Food and Drug Administration in the US approved radiation protection agents cannot be widely used due to their side effects. Some natural nontoxic compounds such as bee products have been reported to prevent and treat radiation-induced injuries (e.g. scavenging free radicals, inhibiting cell apoptosis and reducing DNA damage), indicating that they may be a potential option as a safe radioprotective agent. Bee products are nontoxic and have no known side effects on the human body, and are effective in the field of radiation protection. They are expected to be interesting drug candidates for preventing and treating radiation-induced injuries. This article reviews the prevention and treatment of bee products on radiation-induced injuries. [ABSTRACT FROM AUTHOR]

Uncertainties regarding the magnitude of health effects following exposure to low doses of ionizing radiation remain a matter of concern both for professionals and for the public. There is consensus within the international radiation research community that more research is required on biological effects of radiation doses below 100 mGy applied at low dose rates. Moreover, there is a demand for increasing education and training of future radiation researchers and regulators. Research, education and training is primarily carried out at universities but university-based radiation research is often hampered by limited access to radiation sources. The aim of the present report is to describe small and cost-effective low activity gamma and alpha sources that can easily be installed and used in university laboratories. A gamma radiation source was made from an euxenite-(Y) rock (Y,Ca,Ce,U,Th)(Nb,Ta,Ti)2O6) that was found in an abandoned mine in Sweden. It allows exposing cells grown in culture dishes to radiation at a dose rate of 50 µGy/h and lower. Three alpha sources were custom-made and yield a dose rate of 1 mGy/h each. The construction, dosimetry and cellular effects of the sources are described. We hope that the report will stimulate research and training activities in the low dose field by facilitating access to radiation sources. [ABSTRACT FROM AUTHOR]

The assessment of biological effects caused by radiation exposure has been currently carried out with the linear-quadratic (LQ) model as an extension of the linear non-threshold (LNT) model. In this study, we suggest a new mathematical model named as SeaSaw (SS) model, which describes proliferation and cell death effects by taking account of Bergonie-Tribondeau's law in terms of a differential equation in time. We show how this model overcomes the long-standing difficulties of the LQ model. We construct the SS model as an extended Wack-A-Mole (WAM) model by using a differential equation with respect to time in order to express the dynamics of the proliferation effect. A large number of accumulated data of such parameters as α and β in the LQ based models provide us with valuable pieces of information on the corresponding parameter b 1 and the maximum volume V m of the SS model. The dose rate b 1 and the notion of active cell can explain the present data without introduction of β, which is obtained by comparing the SS model with not only the cancer therapy data but also with in vitro experimental data. Numerical calculations are presented to grasp the global features of the SS model. The SS model predicts the time dependence of the number of active- and inactive-cells. The SS model clarifies how the effect of radiation depends on the cancer stage at the starting time in the treatment. Further, the time dependence of the tumor volume is calculated by changing individual dose strength, which results in the change of the irradiation duration for the same effect. We can consider continuous irradiation in the SS model with interesting outcome on the time dependence of the tumor volume for various dose rates. Especially by choosing the value of the dose rate to be balanced with the total growth rate, the tumor volume is kept constant. The SS model gives a simple equation to study the situation of clinical radiation therapy and risk estimation of radiation. The radiation parameter extracted from the cancer therapy is close to the value obtained from animal experiment in vitro and in vivo. We expect the SS model leads us to a unified description of radiation therapy and protection and provides a great development in cancer-therapy clinical-planning. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the effects of oleuropein radiation protection and to find an effective radioprotector. Human mononuclear cells were treated with oleuropein at the concentration of 100 μM (optimum concentration), incubated for 24 h, and then exposed to 2 Gy gamma-rays. The anti-radiation effect of oleuropein was assessed by MTT assay, flow cytometry, comet assay, and micronucleus (MN) assay. It was found that pretreatment with oleuropein (25, 50, 75, 100, 200, 400, and 800 nM, and 1, 5, 10, 15, 20, 25, 30, 40, 50, 75, 100, 125, 150, 175, and 200 µM) significantly increased the percentage of cell viability compared to the irradiated group (p <.001). Moreover, oleuropein treatment with the above concentrations defined without gamma-ray did not show any cytotoxicity effect in human mononuclear cells. The LD50/24h dose was calculated as 2.9 Gy, whereas by 200, 150, 50, and 100 µM oleuropein prior to radiation (1, 2,and 4 Gy), radiation LD50/24h increased to 3.36, 3.54, 3.81, and >4 Gy, in that order. A very noticeable dose-modifying factor (DMF) of 1.16, 1.23, 1.31, and 1.72 was observed for 200, 150, 50, and 100 µM, in order. Therefore, 100 µM of oleuropein was selected as the desirable dose for radio-protection trial, and 2 Gy gamma-rays were used for further research. Human mononuclear cells treatment with oleuropein (100 µM) prior to 2 Gy gamma-rays significantly decreased apoptosis, genomic damage, and MN occurrence in human mononuclear caused by gamma-radiation (p <.001). Furthermore, treatment with oleuropein (100 µM) without radiation did not lead to apoptosis, genotoxicity, or clastogenic effects caused by oleuropein in human mononuclear cells. The results revealed that oleuropein is able to significantly reduce cytotoxicity, apoptosis, genotoxic, and clastogenic effects of gamma-rays. [ABSTRACT FROM AUTHOR]

The linear-quadratic (LQ) model represents a simple and robust approximation for many mechanistically-motivated models of radiation effects. We believe its tendency to overestimate cell killing at high doses derives from the usual assumption that radiogenic lesions are distributed according to Poisson statistics. In that context, we investigated the effects of overdispersed lesion distributions, such as might occur from considerations of microdosimetric energy deposition patterns, differences in DNA damage complexities and repair pathways, and/or heterogeneity of cell responses to radiation. Such overdispersion has the potential to reduce dose response curvature at high doses, while still retaining LQ dose dependence in terms of the number of mean lethal lesions per cell. Here we analyze several irradiated mammalian cell and yeast survival data sets, using the LQ model with Poisson errors, two LQ model variants with customized negative binomial (NB) error distributions, the Padé-linear-quadratic, and Two-component models. We compared the performances of all models on each data set by information-theoretic analysis, and assessed the ability of each to predict survival at high doses, based on fits to low/intermediate doses. Changing the error distribution, while keeping the LQ dose dependence for the mean, enables the NB LQ model variants to outperform the standard LQ model, often providing better fits to experimental data than alternative models. The NB error distribution approach maintains the core mechanistic assumptions of the LQ formalism, while providing superior estimates of cell survival following high doses used in radiotherapy. Importantly, it could also be useful in improving the predictions of low dose/dose rate effects that are of major concern to the field of radiation protection. [ABSTRACT FROM AUTHOR]

We herein report on changes in gene expression after radiation exposure to iodine-131 from the Chernobyl accident in the Ukrainian-American thyroid cohort and to external gamma ray or internal plutonium exposure in the Mayak Production Association radiation workers. Taking advantage of access to tissue samples from the thyroid cancer cases in the Ukrainian-American cohort, our group tried to identify candidate genes to discriminate spontaneously occurring thyroid cancers from thyroid cancers caused by radiation exposure. We also examined gene expression changes in normal and cancerous thyroid tissue in relation to iodine-131 dose separately. Gene expression changes in the peripheral blood of radiation exposed Mayak workers were examined to elucidate the dose-to-gene and gene-to-health (e.g. cardiovascular disease) relationships. Results of both projects are discussed under the aspect of dose-response relationships (dose-to-gene) and clinical outcome relationships (gene-to-effect) in light of how mechanistic data can be translated into actionable knowledge for radiation protection or clinical purposes. [ABSTRACT FROM AUTHOR]

Despite the vast amount of literature on radiological emergencies, to the best of our knowledge there is no systematic review of probable scenarios and their consequences. This work aimed for compiling such review. The authors comprised a Red Team – that is, simulated best efforts to inflict maximal damage to the society by various means of radiological attacks. Nuclear warfare including improvised nuclear devices is beyond the scope of this work. The direct radiogenic health consequences of any conceivable radiological accident, natural or man-made, are much less dangerous than those which are usually perceived. In each scenario, direct health effects are only a small part of the damage caused by fear and over-reaction; the damage is somewhat independent of the small health effect predicted for most of the scenarios. The reason is that nuclear radiation has become perceptually connected with nuclear apocalypses. This connection has caused the emotional description of radiological emergencies to frequently substitute quantitative considerations. For example, Chernobyl and Fukushima became major humanitarian disasters not because of the radiation itself but because of the over-reaction of both the authorities and the public, that led to the unjustified relocation of hundreds of thousands of people. In Fukushima, the evacuation was not justified at all and in Chernobyl the evacuated zone should have been re-populated after 1 month. It is vital to educate decision makers, first responders and the public about the factual extent of possible radiological consequences, as well as about the very real danger of over-reaction. Since the extent of the countermeasures deployed is unavoidably connected, in the eye of the public, with the extent of the danger, we suggest launching educational campaigns that explain the factual extent of the radiation risk, followed by easing regulations and narrowing safety margins. Such measures will probably be the most efficient method of countering radiological terrorism: by depriving any adversary of the most important ability which is to cause an over-reaction. [ABSTRACT FROM AUTHOR]

We aimed for a quantitative evaluation that justifies guidelines for evacuation which take into consideration both the human and economic costs. To the best of our knowledge, such an evaluation has not been performed yet. The present guidelines published by the International Atomic Energy Agency (IAEA) are probably based on averting radiation risk only; IAEA did not cite any quantitative estimation of the human cost of evacuation. Quantitative estimation of the human and monetary costs of evacuation and, alternatively, the human and monetary costs of radiation exposure (non-evacuation). Associating human life with monetary value is psychologically difficult and somewhat challenging ethically; however, there is no escape from such an association (cost-effectiveness analysis) when making decisions regarding public health and safety, since extraneous public expenditures lead to a statistical life shortening. Estimating worst-case health consequences of irradiation, we used the conservative linear no-threshold (LNT) model because this model is widely used in spite of its controversy. In our estimation of the human cost of evacuation, we considered three factors: (a) direct loss of life (after Fukushima, 1% of the evacuees died within 2 years due to causes directly related to their evacuation), (b) loss of quality of life, and (c) loss of wealth leading to loss of life. The connection of economic loss with loss of life was performed according to the median cost-effectiveness threshold of 50–100 thousand USD per quality-adjusted life year. Even according to mortality calculations based on LNT, the overall loss of life due to evacuation is higher than the loss of life due to irradiation if the population-averaged first-year radiation dose is 500 mSv or less. Based on the performed analysis, we suggest avoiding evacuation if the projected first-year dose is below 500 mSv. This suggested action level is about five-fold higher than the action level presently recommended by the IAEA (100 mSv per year). [ABSTRACT FROM AUTHOR]

Since early April 2020, there has been intense debate over proposed clinical use of ionizing radiation to treat life-threatening pneumonia in Coronavirus Disease 2019 (COVID-19) patients. At least twelve relevant papers appeared by 20 May 2020. The radiation dose proposed for clinical trials are a single dose (0.1–1 Gy) or two doses (a few mGy followed by 0.1–0.25 Gy involving a putative adaptive response, or 1–1.5 Gy in two fractions 2–3 days apart). The scientific rationale for such proposed so-called low dose radiotherapy (LDRT) is twofold (note that only doses below 0.1 Gy are considered as low doses in the field of radiation protection, but here we follow the term as conventionally used in the field of radiation oncology). Firstly, the potentially positive observations in human case series and biological studies in rodent models on viral or bacterial pneumonia that were conducted in the pre-antibiotic era. Secondly, the potential anti-inflammatory properties of LDRT, which have been seen when LDRT is applied locally to subacute degenerative joint diseases, mainly in Germany. However, the human and animal studies cited as supportive evidence have significant limitations, and whether LDRT produces anti-inflammatory effects in the inflamed lung or exacerbates ongoing COVID-19 damage remains unclear. Therefore, we conclude that the available scientific evidence does not justify clinical trials of LDRT for COVID-19 pneumonia, with unknown benefit and known mortality risks from radiogenic cancer and circulatory disease. Despite the significant uncertainties in these proposals, some clinical trials are ongoing and planned. This paper gives an overview of current situations surrounding LDRT for COVID-19 pneumonia. [ABSTRACT FROM AUTHOR]

Purpose: Radiation risk communication is a critical component of radiation protection and the public's understanding of radiation risks and benefits. Risk communication becomes even more complicated when considering cultural and language differences. In the US, many diverse communities face risk communication challenges. We obtained radon testing data to evaluate patterns of radon testing in Allentown, the third largest city in Pennsylvania. Radon exposure is the second leading cause of lung cancer after smoking and is associated with over 21,000 lung cancer deaths in the US annually. It is estimated that 1 in every 15 homes in the US has elevated radon levels above the recommended action level set by the US Environmental Protection Agency. Allentown has some of the highest reported levels of indoor radon in the country, yet only a small portion of the population has tested their homes. This is true particularly among self-identified Hispanics, who make up nearly half of the city's population. This study seeks to (1) characterize the difference in testing rates between self-identified Hispanics and non-Hispanics in Allentown, (2) quantify the level of radon awareness and knowledge, (3) identify potential obstacles to radon testing among the Allentown population that self-identifies as Hispanic, and (4) determine whether more effective risk communication is needed. Method: Radon test results in Allentown were analyzed to better understand the nature of radon testing. To evaluate radon awareness and knowledge, a cross-sectional study was conducted using a face-to-face survey. This data was informative in assessing testing and mitigation practices, ethnicity, income level, age, education level, homeowner status, zip code and primary language. Results: Ethnicity was an independent predictor of radon awareness and knowledge. Statistically significant differences were found between the number of self-identified Hispanics (39%) and non-Hispanics (84%) who indicated that they had ever heard of radon; 13% of Hispanics and 49% of non-Hispanics knew that they lived in an area with typically high radon levels. There was a statistically significant association between self-reported ethnicity and radon testing with non-Hispanics (43%) more likely to test their homes for radon than Hispanics (32%). Conclusion: Individual and community understanding of the risks of exposure to radiation sources such as radon is dependent upon communication that informs and spurs appropriate action. This study demonstrates the need for culturally appropriate radon risk communication strategies targeted to a Hispanic population. Successful communication will raise awareness and knowledge that can lead to better public health protection. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this manuscript is to evaluate the role of regulatory limits and regulatory action on the total impact of nuclear contamination and accidents. While it is important to protect the public from excessive radiation exposures it is also critical to weigh the damage done by implementing regulations against the benefits produced. Two cases: Actions taken as a result of radioactive fallout in Washington County, Utah in 1953 from the atomic bomb testing in Nevada, and the actions implemented post release of radioactive materials into the environment from the damaged nuclear power reactor at Fukushima, Japan, are compared. Materials and methods: The Washington County radiation exposures and doses, resulting from the Nevada nuclear weapons tests, were taken from published reports, papers, and historical records. The protective actions taken were reviewed and reported. Recent publications were used to define the doses following Fukushima. The impact and/or results of sheltering only versus sheltering/evacuation of Washington County and Fukushima are compared. Results: The radiation dose from the fallout in Washington County from the fallout was almost 2–3 three times the dose in Japan, but the regulatory actions were vastly different. In Utah, the minimal action taken, e.g. sheltering in place, had no major impact on the public health or on the economy. The actions in Fukushima resulted in major negative impact precipitated through the fear generated. And the evacuation. The results had adverse human health and wellness consequences and a serious impact on the economy of the Fukushima region, and all of Japan. Conclusions: When evacuation is being considered, great care must be taken when any regulatory actions are initiated based on radiation limits. It is necessary to consider total impact and optimize the actions to limit radiation exposure while minimizing the social, economic, and health impacts. Optimization can help ensure that the protective measures result in more good than harm. It seems clear that organizations who recommend radiation protection guidelines need to revisit the past and current guides in light of the significant Fukushima experience. [ABSTRACT FROM AUTHOR]

Purpose: Humans are increasingly exposed to ionizing radiation (IR). Both low (<100 mGy) and high doses can cause stochastic effects, including cancer; whereas doses above 100 mGy are needed to promote tissue or cell damage. 10–15% of radiotherapy (RT) patients suffer adverse reactions, described as displaying radiosensitivity (RS). Sensitivity to IR's stochastic effects is termed radiosusceptibility (RSu). To optimize radiation protection we need to understand the range of individual variability and underlying mechanisms. We review the potential mechanisms contributing to RS/RSu focusing on RS following RT, the most tractable RS group. Conclusions: The IR-induced DNA damage response (DDR) has been well characterized. Patients with mutations in the DDR have been identified and display marked RS but they represent only a small percentage of the RT patients with adverse reactions. We review the impacting mechanisms and additional factors influencing RS/RSu. We discuss whether RS/RSu might be genetically determined. As a recommendation, we propose that a prospective study be established to assess RS following RT. The study should detail tumor site and encompass a well-defined grading system. Predictive assays should be independently validated. Detailed analysis of the inflammatory, stress and immune responses, mitochondrial function and life style factors should be included. Existing cohorts should also be optimally exploited. [ABSTRACT FROM AUTHOR]

Purpose: To summarize existing knowledge and to understand individual response to radiation exposure, the MELODI Association together with CONCERT European Joint Programme has organized a workshop in March 2018 on radiation sensitivity and susceptibility. Methods: The workshop reviewed the current evidence on this matter, to inform the MELODI Strategic Research Agenda (SRA), to determine social and scientific needs and to come up with recommendations for suitable and feasible future research initiatives to be taken for the benefit of an improved medical diagnosis and treatment as well as for radiation protection. Results: The present paper gives an overview of the current evidence in this field, including potential effect modifiers such as age, gender, genetic profile, and health status of the exposed population, based on clinical and epidemiological observations. Conclusion: The authors conclude with the following recommendations for the way forward in radiation research: (a) there is need for large (prospective) cohort studies; (b) build upon existing radiation research cohorts; (c) use data from well-defined cohorts with good exposure assessment and biological material already collected; (d) focus on study quality with standardized data collection and reporting; (e) improve statistical analysis; (f) cooperation between radiobiology and epidemiology; and (g) take consequences of radiosensitivity and radiosusceptibility into account. [ABSTRACT FROM AUTHOR]