Epidemiological studies of cataract risk at low to moderate radiation doses: (not) seeing is believing

The prevailing belief for some decades has been that human radiation-related cataract occurs only after relatively high doses; for instance, the ICRP estimates that brief exposures of at least 0.5-2 Sv are required to cause detectable lens opacities and 5 Sv for vision-impairing cataracts. For protracted exposures, the ICRP estimates the corresponding dose thresholds as 5 Sv and 8 Sv, respectively. However, several studies, especially in the last decade, indicate that radiation-associated opacities occur at much lower doses. Several studies suggest that medical or environmental radiation exposure to the lens confers risk of opacities at doses well under 1 Sv. Among Japanese A-bomb survivors, risks for cataracts necessitating lens surgery were seen at doses under 1 Gy. The confidence interval on the A-bomb dose threshold for cataract surgery prevalence indicated that the data are compatible with a dose threshold ranging from none up to only 0.8 Gy, similar to the dose threshold for minor opacities seen among Chernobyl clean-up workers with primarily protracted exposures. Findings from various studies indicate that radiation risk estimates are probably not due to confounding by other cataract risk factors and that risk is seen after both childhood and adult exposures. The recent data are instigating reassessments of guidelines by various radiation protection bodies regarding permissible levels of radiation to the eye. Among the future epidemiological research directions, the most important research need is for adequate studies of vision-impairing cataract after protracted radiation exposure.     

Molecular and cellular biology of moderate-dose (1-10 Gy) radiation and potential mechanisms of radiation protection: report of a workshop at Bethesda,Maryland, December 17-18, 2001

Exposures to doses of radiation of 1-10 Gy, defined in this workshop as moderate-dose radiation, may occur during the course of radiation therapy or as the result of radiation accidents or nuclear/radiological terrorism alone or in conjunction with bioterrorism. The resulting radiation injuries would be due to a series of molecular, cellular, tissue and whole-animal processes. To address the status of research on these issues, a broad-based workshop was convened. The specific recommendations were: (1) Research: Identify the key molecular, cellular and tissue pathways that lead from the initial molecular lesions to immediate and delayed injury. The latter is a chronic progressive process for which postexposure treatment may be possible. (2) Technology: Develop high-throughput technology for studying gene, protein and other biochemical expression after radiation exposure, and cytogenetic markers of radiation exposure employing rapid and accurate techniques for analyzing multiple samples. (3) Treatment strategies: Identify additional biological targets and develop effective treatments for radiation injury. (4) Ensuring sufficient expertise: Recruit and train investigators from such fields as radiation biology, cancer biology, molecular biology, cellular biology and wound healing, and encourage collaboration on interdisciplinary research on the mechanisms and treatment of radiation injury. Communicate knowledge of the effects of radiation exposure to the general public and to investigators, policy makers and agencies involved in response to nuclear accidents/events and protection/treatment of the general public.     

Occupational exposure to low doses of ionizing radiation and cataract development: a systematic literature review and perspectives on future studies

Ionizing radiation is a well-known but little understood risk factor for lens opacities. Until recently, cataract development was considered to be a deterministic effect occurring at lens doses exceeding a threshold of 5–8 Gy. Substantial uncertainty about the level and the existence of a threshold subsists. The International Commission on Radiation Protection recently revised it to 0.5 Gy. Based on a systematic literature review of epidemiological studies on exposure to low levels of ionizing radiation and the occurrence of lens opacities, a list of criteria for new epidemiological studies was compiled, and a list of potential study populations was reviewed. Among 24 publications finally identified, six report analyses of acute exposures in atomic bomb survivors and Chernobyl liquidators, and the others report analyses of protracted exposures in occupationally, medically or accidentally exposed populations. Three studies investigated a dose threshold: in atomic bomb survivors, the best estimates were 1 Sv (95 % CI <0–0.8 Sv) regarding lensectomies; in survivors exposed as children, 0.6 Sv (90 % CI <0.0–1.2 Sv) for cortical cataract prevalence and 0.7 Sv (90 % CI 0.0–2.8 Sv) for posterior subcapsular cataract; and in Chernobyl liquidators, 0.34 Sv (95 % CI 0.19–0.68 Sv) for stage 1 cataract. Current studies are heterogeneous and inconclusive regarding the dose–response relationship. Protracted exposures and high lens doses occur in several occupational groups, for instance, in physicians performing fluoroscopy-guided interventional procedures, and in accidentally exposed populations. New studies with a good retrospective exposure assessment are feasible and should be initiated.     

Failla memorial lecture. Risk, research, and radiation protection

Radiation protection concerns the risk of stochastic late effects, especially cancer, and limits on radiation exposure both occupationally and for the public tend to be based on these risks. The risks are determined, mainly by expert committees, from the steadily growing information on exposed human populations, especially the survivors of the atomic bombs dropped in Japan in 1945. Risks of cancer estimated up to the early 1980s were in the range 1 to 5 X 10(-2)/Sv, but recent revisions in the dosimetry of the Japanese survivors and additional cycles of epidemiological information suggest values now probably at the high end of this range. These are likely to require an increase in the values used for radiation protection. A major problem with risk estimation is that data are available only for substantial doses and must be extrapolated down to the low-dose region of interest in radiation protection. Thus the shape of the dose-response curve is important, and here we must turn to laboratory research. Of importance are studies involving (1) dose rate, which affects the response to low-LET radiation and often to high-LET radiation as well; (2) radiation quality, since the shapes of the dose-response curves for high- and low-LET radiation differ and thus the RBE, the ratio between them, varies, reaching a maximum value RBEM at low doses; and (3) modifiers of the carcinogenic response, which either enhance or reduce the effect of a given dose. Radiation protection depends both on risk information, and especially also on comparisons with other occupational and public risks, and on research, not only for extrapolations of risk to low doses but also in areas where human information is lacking such as in the effects of radiation quality and in modifications of response.     

Current status of cytogenetic procedures to detect and quantify previous exposures to radiation

The estimation of the magnitude of a dose of ionizing radiation to which an individual has been exposed (or of the plausibility of an alleged exposure) from chromosomal aberration frequencies determined in peripheral blood lymphocyte cultures is a well-established methodology, having first been employed over 25 years ago. The cytogenetics working group has reviewed the accumulated data and the possible applicability of the technique to the determination of radiation doses to which American veterans might have been exposed as participants in nuclear weapons tests in the continental U.S.A. or the Pacific Atolls during the late 1940s and 1950s or as members of the Occupation Forces entering Hiroshima or Nagasaki shortly after the nuclear detonations there. The working group believes that with prompt peripheral blood sampling, external doses to individuals of the order of about 10 rad (or less if the exposure was to high-LET radiation) can accurately be detected and measured. It also believes that exposures of populations to doses of the order of maximum permissible occupational exposures can also be detected (but only in populations; not in an individual). Large exposures of populations can also be detected even several decades after their exposure, but only in the case of populations, and of large doses (of the order of 100 to several hundred rad). The working group does not believe that cytogenetic measurements can detect internal doses from fallout radionuclides in individuals unless these are very large. The working group has approached the problem of detection of small doses (less than or equal to 10 or so rad) sampled decades after the exposure of individuals by using a Bayesian statistical approach. Only a preliminary evaluation of this approach was possible, but it is clear that it could provide a formal statement of the likelihood that any given observation of a particular number of chromosomal aberrations in a sample of any particular number of lymphocytes actually indicates an exposure to any given dose of radiation. It is also clear that aberration frequencies (and consequently doses) would have to be quite high before much confidence could be given to either exposure or dose estimation by this method, given the approximately 3 decades of elapsed time between the exposures and any future blood sampling.(ABSTRACT TRUNCATED AT 400 WORDS)     

Esophagus cancer and radiation exposure due to nuclear test fallout: an analysis based on the data of the Semipalatinsk historical cohort, 1960-1999

This paper describes the Semipalatinsk historical cohort study and, in particular, examines the association between combined external and internal radiation exposure and esophagus cancer. Esophagus cancer is the most frequent single cancer site in the cause of death follow-up for the Semipalatinsk cohort. Set up in the 1960s, this historical cohort included 10 exposed settlements in the vicinity of the Semipalatinsk nuclear test site in East Kazakhstan as well as 6 comparison settlements in a low exposure area of the same region. The external and internal radiation doses to the population of the settlements under study were mainly due to local fallout from atmospheric nuclear testing (1949-1962). The database includes dosimetry and health information for 19.545 inhabitants of exposed and comparison villages in the Semipalatinsk region, comprising a total of 582.750 person-years of follow-up between 1960 and 1999. Cumulative effective dose estimates in this cohort range from 20 mSv to -4 Sv, with a mean dose of 634 mSv in the exposed group. Relative risks were calculated in terms of rate ratios, using a Poisson regression model for grouped person-time data. Esophagus cancer was found substantially elevated, with a statistically significant increase of the relative risk with dose and an ERR/Sv of 2.37 (1.45; 3.28) for the total cohort. If the data set was restricted to the exposed group only, the ERR/Sv was found considerably lower (0.18 (-0.16; 0.52)), whereas the dose-response remained significant only in women. Overall, our results based on the Semipalatinsk historical cohort indicate an association between fallout exposure and the risk of esophagus cancer that should be further investigated.     

Radioepidemiology in the aftermath of the nuclear program of the former Soviet Union: Unique lessons to be learnt

  The military and civilian nuclear activities in the former Soviet Union led to unique exposures and resulted in high cumulative doses in several populations. In comparison to the atomic bomb survivors, at present the most important cohort in radiation epidemiology, collective and individual doses received by early workers in the plutonium production facilities at Mayak (Chelyabinsk), Techa River residents downstream of Mayak, populations downwind of the Semipalatinsk test site, and subpopulations of Chernobyl victims surpass the Hiroshima/Nagasaki experience in most cases. Even more importantly, the dose rates cover the full range of exposures relevant for radiation protection, i.e., acute to year-long chronic exposures from environmental contamination and bone seeking radionuclides. Parallel to the humanitarian need to mitigate health effects from these exposures, the unique opportunities for research on radiation risks related to low dose rate and chronic radiation have to be explored. Increased efforts by the global radiation research community are needed to address the many questions which cannot be answered by the acutely irradiated survivors of Hiroshima/Nagasaki. Specific attention needs to be drawn to the validation of available exposure and health records and to dose reconstruction which must include dietary sources of exposure. Preliminary intercomparison and validation exercises indicate potentially large sources of error, e.g., due to uncertainties in the reconstruction of early exposures and effects and due to continuing incorporation. Received: 29 February 1996 / Accepted in revised form: 6 March 1996     

Low doses of ionizing radiation and circulatory diseases: a systematic review of the published epidemiological evidence

Recent analyses of mortality among atomic bomb survivors have suggested a linear dose-response relationship between ionizing radiation and diseases of the circulatory system for exposures in the range 0-4 Sv. If confirmed, this has substantial implications. We have therefore reviewed the published literature to see if other epidemiological data support this finding. Other studies allowing a comparison of the rates of circulatory disease in individuals drawn from the same population but exposed to ionizing radiation at different levels within the range 0-5 Gy or 0-5 Sv were identified through systematic literature searches. Twenty-six studies were identified. In some, disease rates among those exposed at different levels may have differed for reasons unrelated to radiation exposure, while many had low power to detect effects of the relevant magnitude. Among the remainder, one study found appreciable evidence that exposure to low-dose radiation was associated with circulatory diseases, but five others, all with appreciable power, did not. We conclude that the other epidemiological data do not at present provide clear evidence of a risk of circulatory diseases at doses of ionizing radiation in the range 0-4 Sv, as suggested by the atomic bomb survivors. Further evidence is needed to characterize the possible risk.     

Cancer morbidity and mortality among the liquidators of the Chernobyl accident: estimation of radiation risks

The work focuses on the results of the analysis of the cancer incidence among the Chernobyl emergency workers residing in Russia during 1991-2001. The analysis is based on the data for the cohort of male emergency workers from 6 regions of Russia including 55718 persons with documented external radiation doses in the range of 0.001-0.3 Gy who worked within the 30-km zone in 1986-1987. The mean age at exposure for these persons was 34.8 years old and the mean external radiation dose 0.13 Gy. In this cohort 1370 cases of solid cancer were diagnosed. Three follow-up periods were considered: 1991-1995, 1996-2001 and 1991-2001. The second follow-up period was chosen to allow for a minimum latency period of 10 years. Risk assessments were performed for two control groups: the first control group ("external") represented incidence rates for corresponding ages in Russia in general and the second control group ("internal") consisted of emergency workers. The estimated standardized incidence ratio (SIR) is in good agreement with that of the control within 95% CI. The values of the excess relative risk per unit dose 1 Gy (ERR/Gy) for solid malignant neoplasms have been estimated to be 0.33 (95% CI: -0.39, 1.22) (internal control) for the follow-up period 1991-2001 and 0.19 (95% CI: -0.66, 1.27) for 1996-2001. The analysis of cancer morbidity was carried out for the cohort of 29003 emergency workers who took part in liquidation of the consequences of the Chernobyl accident from 26 April 1986 to 25 April 1987. It was shown that the excess relative risk of cancer deaths per unit dose 1 Sv (ERR/Sv) is equal to 1.52 (95% CI: 0.20, 2.85).     

Education and training for radiation scientists: radiation research program and American Society of Therapeutic Radiology and Oncology Workshop, Bethesda, Maryland, May 12-14, 2003

Current and potential shortfalls in the number of radiation scientists stand in sharp contrast to the emerging scientific opportunities and the need for new knowledge to address issues of cancer survivorship and radiological and nuclear terrorism. In response to these challenges, workshops organized by the Radiation Research Program (RRP), National Cancer Institute (NCI) (Radiat. Res. 157, 204-223, 2002; Radiat. Res. 159, 812-834, 2003), and National Institute of Allergy and Infectious Diseases (NIAID) (Nature, 421, 787, 2003) have engaged experts from a range of federal agencies, academia and industry. This workshop, Education and Training for Radiation Scientists, addressed the need to establish a sustainable pool of expertise and talent for a wide range of activities and careers related to radiation biology, oncology and epidemiology. Although fundamental radiation chemistry and physics are also critical to radiation sciences, this workshop did not address workforce needs in these areas. The recommendations include: (1) Establish a National Council of Radiation Sciences to develop a strategy for increasing the number of radiation scientists. The strategy includes NIH training grants, interagency cooperation, interinstitutional collaboration among universities, and active involvement of all stakeholders. (2) Create new and expanded training programs with sustained funding. These may take the form of regional Centers of Excellence for Radiation Sciences. (3) Continue and broaden educational efforts of the American Society for Therapeutic Radiology and Oncology (ASTRO), the American Association for Cancer Research (AACR), the Radiological Society of North America (RSNA), and the Radiation Research Society (RRS). (4) Foster education and training in the radiation sciences for the range of career opportunities including radiation oncology, radiation biology, radiation epidemiology, radiation safety, health/government policy, and industrial research. (5) Educate other scientists and the general public on the quantitative, basic, molecular, translational and applied aspects of radiation sciences.     

Analysis of the contribution of forest pathways to the radiation exposure of different population groups in the Bryansk region of Russia

The experience gained in the aftermath of serious radiation accidents shows that forests are an important source of external and internal exposure of the affected population. This paper presents the results of an assessment of the major radiological consequences for forests of Russia, most heavily contaminated after the Chernobyl nuclear power plant (ChNPP) accident. Illustrated in the Novozybkovsky district of the Russian Federation, the significance of different forest exposure pathways is estimated and the doses resulting from forest pathways are compared with the doses from agricultural products. It has been found that the contribution of mushrooms and berries to the internal doses of the population, relative to the doses from agricultural products, varied from 10–15% in 1987 to 40–45% in 1996. The results indicate large differences in internal exposure of members of the ”critical groups” and ”normal population”, increasing with time after deposition. Data are presented that give information on the contribution of forests to the collective doses of inhabitants of the area under consideration. It has been shown that for 10 years after the accident (1987–1996), the contribution of forest products to the collective dose of the rural population living in contaminated forests of the Novozybkovsky district, amounts to about 20% (213 person Sv) of the total collective dose of internal and external exposures. However, a potential impact of these products including the dose from exported products is much higher and might reach 659 person Sv. It has been found that in the long-term after the ChNPP accident, serious attention should be given to forest countermeasures, and restoration strategies should be selected on the basis of a combined analysis of the effectiveness of forest and agricultural countermeasures. Received: 16 March 2000 / Accepted: 10 September 2000     

Genomic damage in children accidentally exposed to ionizing radiation: a review of the literature

During the last decade, our knowledge of the mechanisms by which children respond to exposures to physical and chemical agents present in the environment, has significantly increased. Results of recent projects and programmes focused on children's health underline a specific vulnerability of children to environmental genotoxicants. Environmental research on children predominantly investigates the health effects of air pollution while effects from radiation exposure deserve more attention. The main sources of knowledge on genome damage of children exposed to radiation are studies performed after the Chernobyl nuclear plant accident in 1986. The present review presents and discusses data collected from papers analyzing genome damage in children environmentally exposed to ionizing radiation. Overall, the evidence from the studies conducted following the Chernobyl accident, nuclear tests, environmental radiation pollution and indoor accidental contamination reveals consistently increased chromosome aberration and micronuclei frequency in exposed than in referent children. Future research in this area should be focused on studies providing information on: (a) effects on children caused by low doses of radiation; (b) effects on children from combined exposure to low doses of radiation and chemical agents from food, water and air; and (c) specific effects from exposure during early childhood (radioisotopes from water, radon in homes). Special consideration should also be given to a possible impact of a radiochemical environment to the development of an adaptive response for genomic damage. Interactive databases should be developed to provide integration of cytogenetic data, childhood cancer registry data and information on environmental contamination. The overall aim is to introduce timely and efficient preventive measures, by means of a better knowledge of the early and delayed health effects in children resulting from radiation exposure.     

Medical countermeasures for platelet regeneration after radiation exposure. Report of a workshop and guided discussion sponsored by the National Institute of Allergy and Infectious Diseases, Bethesda, MD, March 22–23, 2010

The events of September 11, 2001 and their aftermath increased awareness of the need to develop medical countermeasures (MCMs) to treat potential health consequences of a radiation accident or deliberate attack. The medical effects of lethal exposures to ionizing radiation have been well described and affect multiple organ systems. To date, much of the research to develop treatments for mitigation of radiation-induced hematopoietic damage has focused on amelioration of radiation-induced neutropenia, which has long been considered to be the primary factor in determining survival after an unintentional radiation exposure. Consistent with historical data, recent studies have highlighted the role that radiation-induced thrombocytopenia plays in radiation mortality, yet development of MCMs to mitigate radiation damage to the megakaryocyte lineage has lagged behind anti-neutropenia approaches. To address this gap and to foster research in the area of platelet regeneration after radiation exposure, the National Institute of Allergy and Infectious Diseases (NIAID) sponsored a workshop on March 22-23, 2010 to encourage collaborations between NIAID program awardees and companies developing pro-platelet approaches. NIAID also organized an informal, open discussion between academic investigators, product development contractors, and representatives from the U.S. Food and Drug Administration (FDA) and other relevant government agencies about drug development toward FDA licensure of products for an acute radiation syndrome indication. Specific emphasis was placed on the challenges of product licensure for radiation/nuclear MCMs using current FDA regulations (21 CFR Parts 314 and 601) and on the importance of animal efficacy model development, design of pivotal protocols, and standardization of irradiation and animal supportive care.     

Trends in childhood leukaemia in the Nordic countries in relation to fallout from atmospheric nuclear weapons testing.

OBJECTIVE--To obtain further information about the risks of childhood leukaemia after exposure to ionising radiation at low doses and low dose rates before or after birth or to the father''s testes shortly before conception. DESIGN--Observational study of trends in incidence of childhood leukaemia in relation to estimated radiation exposures due to fallout from atmospheric nuclear weapons testing during the 1950s and 1960s. SETTING--Nordic countries. SUBJECTS--Children aged under 15 years. MAIN OUTCOME MEASURES--Incidence rates of leukaemia by age at diagnosis, sex, country, and calendar year of diagnosis or year of birth; exposure category; relation between leukaemia and exposure for children aged 0-14 and 0-4 separately. RESULTS--During the high fallout period the average estimated dose equivalent to the fetal red bone marrow was around 140 mu Sv and the average annual testicular dose 140 mu Sv. There was little evidence of increased incidence of leukaemia among children born in these years. Doses to the red bone marrow of a child after birth were higher, and during the high exposure period children would have been subjected to an additional dose equivalent of around 1500 mu Sv, similar to doses received by children in several parts of central and eastern Europe owing to the Chernobyl accident and about 50% greater than the annual dose equivalent to the red bone marrow of a child from natural radiation. leukaemia incidence and red marrow dose was not related overall, but rates of leukaemia in the high exposure period were slightly higher than in the surrounding medium exposure period (relative risk for ages 0-14: 1.07, 95% confidence interval 1.00 to 1.14; for ages 0-4: 1.11, 1.00 to 1.24). CONCLUSIONS--Current predicted risks of childhood leukaemia after exposure to radiation are not greatly underestimated for low dose rate exposures.     

Radiation-induced bystander effects and adaptive responses--the Yin and Yang of low dose radiobiology?

Our current knowledge of the mechanisms underlying the induction of bystander effects by low doses of high or low LET ionizing radiation is reviewed. The question of what actually constitutes a protective effect is discussed in the context of adaptive (often referred to as hormetic or protective) responses. Finally the review considers critically, how bystander effects may be related to observed adaptive responses or other seemingly protective effects of low doses exposures. Bystander effects induce responses at the tissue level, which are similar to generalized stress responses. Most of the work involving low LET radiation exposure discussed in the existing literature measures a death response. Since many cell populations carry damaged cells without being exposed to radiation (so-called "background damage"), it is possible that low doses exposures cause removal of cells carrying potentially problematic lesions, prior to exposure to radiation. This mechanism could lead to the production of "U-shaped" or hormetic dose-response curves. The level of adverse, adaptive or apparently beneficial response will be related to the background damage carried by the original cell population, the level of organization at which damage or harm are scored and the precise definition of "harm". This model may be important when attempting to predict the consequences of mixed exposures involving low doses of radiation and other environmental stressors.     

Mitochondrial DNA mutations in individuals occupationally exposed to ionizing radiation

Mutations in a 443-bp amplicon of the hypervariable region HVR1 of the D-loop of mitochondrial DNA (mtDNA) were quantified in DNA extracted from peripheral blood samples of 10 retired radiation workers who had accumulated external radiation doses of >0.9 Sv over the course of their working life and were compared to the levels of mutations in 10 control individuals matched for age and smoking status. The mutation rate in the 10 exposed individuals was 9.92 x 10(-5) mutations/ nucleotide, and for the controls it was 8.65 x 10(-5) mutations/ nucleotide, with a procedural error rate of 2.65 x 10(-5) mutations/nucleotide. No increase in mtDNA mutations due to radiation exposure was detectable (P = 0.640). In contrast, chromosomal translocation frequencies, a validated radiobiological technique for retrospective dosimetric purposes, were significantly elevated in the exposed individuals. This suggests that mutations identified through sequencing of mtDNA in peripheral blood lymphocytes do not represent a promising genetic marker of DNA damage after low-dose or low-dose-rate exposures to ionizing radiation. There was an increase in singleton mutations above that attributable to procedural error in both exposed and control groups that is likely to reflect age-related somatic mutation.     

Medical countermeasures for radiation combined injury: radiation with burn, blast, trauma and/or sepsis. report of an NIAID Workshop, March 26-27, 2007

Non-clinical human radiation exposure events such as the Hiroshima and Nagasaki bombings or the Chernobyl accident are often coupled with other forms of injury, such as wounds, burns, blunt trauma, and infection. Radiation combined injury would also be expected after a radiological or nuclear attack. Few animal models of radiation combined injury exist, and mechanisms underlying the high mortality associated with complex radiation injuries are poorly understood. Medical countermeasures are currently available for management of the non-radiation components of radiation combined injury, but it is not known whether treatments for other insults will be effective when the injury is combined with radiation exposure. Further research is needed to elucidate mechanisms behind the synergistic lethality of radiation combined injury and to identify targets for medical countermeasures. To address these issues, the National Institute of Allergy and Infectious Diseases convened a workshop to make recommendations on the development of animal models of radiation combined injury, possible mechanisms of radiation combined injury, and future directions for countermeasure research, including target identification and end points to evaluate treatment efficacy.     

Updated mortality analysis of radiation workers at Rocketdyne (Atomics International), 1948-2008

Updated analyses of mortality data are presented on 46,970 workers employed 1948-1999 at Rocketdyne (Atomics International). Overall, 5,801 workers were involved in radiation activities, including 2,232 who were monitored for intakes of radionuclides, and 41,169 workers were engaged in rocket testing or other non-radiation activities. The worker population is unique in that lifetime occupational doses from all places of employment were sought, updated and incorporated into the analyses. Further, radiation doses from intakes of 14 different radionuclides were calculated for 16 organs or tissues using biokinetic models of the International Commission on Radiation Protection (ICRP). Because only negligible exposures were received by the 247 workers monitored for radiation activities after 1999, the mean dose from external radiation remained essentially the same at 13.5 mSv (maximum 1 Sv) as reported previously, as did the mean lung dose from external and internal radiation combined at 19.0 mSv (maximum 3.6 Sv). An additional 9 years of follow-up, from December 31,1999 through 2008, increased the person-years of observation for the radiation workers by 21.7% to 196,674 (mean 33.9 years) and the number of cancer deaths by 50% to 684. Analyses included external comparisons with the general population and the computation of standardized mortality ratios (SMRs) and internal comparisons using proportional hazards models and the computation of relative risks (RRs). A low SMR for all causes of death (SMR 0.82; 95% CI 0.78-0.85) continued to indicate that the Rocketdyne radiation workers were healthier than the general population and were less likely to die. The SMRs for all cancers taken together (SMR 0.88; 95% CI 0.81-0.95), lung cancer (SMR 0.87; 95% CI 0.76-1.00) and leukemia other than chronic lymphocytic leukemia (CLL) (SMR 1.04; 95% 0.67-1.53) were not significantly elevated. Cox regression analyses revealed no significant dose-response trends for any cancer. For all cancers excluding leukemia, the RR at 100 mSv was estimated as 0.98 (95% CI 0.82-1.17), and for all leukemia other than CLL it was 1.06 (95% CI 0.50-2.23). Uranium was the primary radionuclide contributing to internal exposures, but no significant increases in lung and kidney disease were seen. The extended follow-up reinforces the findings in the previous study in failing to observe a detectable increase in cancer deaths associated with radiation, but strong conclusions still cannot be drawn because of small numbers and relatively low career doses. Larger combined studies of early workers in the United States using similar methodologies are warranted to refine and clarify radiation risks after protracted exposures.     

Justification and optimization of radiation exposures: a new framework to aggregate arbitrary detriments and benefits

Myriad radiation effects, including benefits and detriments, complicate justifying and optimizing radiation exposures. The purpose of this study was to develop a comprehensive conceptual framework and corresponding quantitative methods to aggregate the detriments and benefits of radiation exposures to individuals, groups, and populations. In this study, concepts from the ICRP for low dose were integrated with clinical techniques focused on high dose to develop a comprehensive figure of merit (FOM) that takes into account arbitrary host- and exposure-related factors, endpoints, and time points. The study built on existing methods with three new capabilities: application to individuals, groups, and populations; extension to arbitrary numbers and types of endpoints; and inclusion of limitation, where relevant. The FOM was applied to three illustrative exposure situations: emergency response, diagnostic imaging, and cancer radiotherapy, to evaluate its utility in diverse settings. The example application to radiation protection revealed the FOM’s utility in optimizing the benefits and risks to a population while keeping individual exposures below applicable regulatory limits. Examples in diagnostic imaging and cancer radiotherapy demonstrated the FOM’s utility for guiding population- and patient-specific decisions in medical applications. The major finding of this work is that it is possible to quantitatively combine the benefits and detriments of any radiation exposure situation involving an individual or population to perform cost-effectiveness analyses using the ICRP key principles of radiation protection. This FOM fills a chronic gap in the application of radiation-protection theory, i.e., limitations of generalized frameworks to algorithmically justify and optimize radiation exposures. This new framework potentially enhances objective optimization and justification, especially in complex exposure situations.