No-threshold Research Articles

Death of the ALARA Radiation Protection Principle as Used in the Medical Sector.

ALARA is the acronym for “As Low As Reasonably Achievable.” It is a radiation protection concept borne from the linear no-threshold (LNT) hypothesis. There are no valid data today supporting the use of LNT in the low-dose range, so dose as a surrogate for risk in radiological imaging is not appropriate, and therefore, the use of the ALARA concept is obsolete. Continued use of an outdated and erroneous principle unnecessarily constrains medical professionals attempting to deliver high-quality care to patients by leading to a reluctance by doctors to order images, a resistance from patients/parents to receive images, subquality images, repeated imaging, increased radiation exposures, the stifling of low-dose radiation research and treatment, and the propagation of radiophobia and continued endorsement of ALARA by regulatory bodies. All these factors result from the fear of radiogenic cancer, many years in the future, that will not occur. It has been established that the dose threshold for leukemia is higher than previously thought. A low-dose radiation exposure from medical imaging will likely upregulate the body’s adaptive protection systems leading to the prevention of future cancers. The ALARA principle, as used as a radiation protection principle throughout medicine, is scientifically defunct and should be abandoned.

Zero-Fluoroscopy Ablation at the Texas Heart Institute.

Zero-Fluoroscopy Ablation at the Texas Heart Institute.

Пороговая квадратичная модель зависимости радиационных эффектов от дозы облучения

Introduction. Operation of radiation hazardous facilities is a reality of the modern world, and the future of the world economy is impossible without the development of nuclear and radiation technologies. At the same time, the widespread use of atomic energy puts forward an important and responsible task of ensuring the safety of the population and the environment in conditions of an increased risk of exposure to ionizing radiation and radioactive substances. In accordance with clause 3.2.1 of the "Radiation Safety Standards NRB-99/2009", the planned increased exposure of persons involved in emergency rescue operations related to the elimination of the consequences of radiation accidents is allowed for men, as a rule, over 30 years old only with their voluntary written consent, after informing about possible radiation doses and health risks. Increased exposure refers to exposure in excess of the basic dose limits under controlled (normal) operating conditions of radiation sources. Goals and objectives. The aim of the study is to increase the functionality of emergency services and fire and rescue subdivisions to perform tasks as intended in the elimination of radiation accidents. The tasks include the construction and substantiation of a model that allows converting the risks of deterministic effects into stochastic effects risks. Methods. When calculating the probability of output of stochastic and deterministic effects depending on the radiation dose and developing a threshold quadratic model, the least squares method and the probabilistic-statistical method were used. Results and discussion. The article shows that a linear non-threshold model of the interaction of radiation with matter greatly overestimates the risk of a stochastic effect emerging at doses of radiation. For example, this overestimation is 8,13 at a dose of D = 0,2 Sv/year. In this regard, a threshold quadratic model has been developed and proposed to be replaced by a threshold quadratic model, which makes it possible to increase the planned irradiation of personnel of emergency services and fire and rescue units during the elimination of radiation accidents in an effective dose from 0,2 Sv to 0,57 Sv, moreover, the probability of emergence of stochastic effects P2 = 0,0084 remains the same for both models. Conclusions. An increase in the maximum permissible dose of radiation for personnel of emergency services and fire and rescue units from 0,2 Sv/year to 0,5 Sv/year will make it possible to increase the functionality of the emergency services and fire and rescue units to perform tasks as intended by 2,5 times when elimination of radiation accidents. For example, the scope of rescue operations may be increased from 100 %, performed at a dose of D = 0,2 Sv/year, to 250 %, performed at a dose of D = 0,5 Sv/year. Key words: emergency services, fire and rescue units, radiation accidents, irradiation, linear no-threshold model, threshold quadratic model.

Radio-biologically motivated modeling of radiation risks of mortality from ischemic heart diseases in the Canadian fluoroscopy cohort study.

Recent analyses of the Canadian fluoroscopy cohort study reported significantly increased radiation risks of mortality from ischemic heart diseases (IHD) with a linear dose-response adjusted for dose fractionation. This cohort includes 63,707 tuberculosis patients from Canada who were exposed to low-to-moderate dose fractionated X-rays in 1930s-1950s and were followed-up for death from non-cancer causes during 1950-1987. In the current analysis, we scrutinized the assumption of linearity by analyzing a series of radio-biologically motivated nonlinear dose-response models to get a better understanding of the impact of radiation damage on IHD. The models were weighted according to their quality of fit and were then mathematically superposed applying the multi-model inference (MMI) technique. Our results indicated an essentially linear dose-response relationship for IHD mortality at low and medium doses and a supra-linear relationship at higher doses (> 1.5Gy). At 5Gy, the estimated radiation risks were fivefold higher compared to the linear no-threshold (LNT) model. This is the largest study of patients exposed to fractionated low-to-moderate doses of radiation. Our analyses confirm previously reported significantly increased radiation risks of IHD from doses similar to those from diagnostic radiation procedures.

One-Decade-Spanning transgenerational effects of historic radiation dose in wild populations of bank voles exposed to radioactive contamination following the chernobyl nuclear disaster

The concept of historic radiation doses associated with accidental radioactive releases and their role in leading to radiation-induced non-targeted effects on affected wild animals are currently being evaluated. Previous research studying Fukushima butterfly, Chernobyl bird and fruit fly populations shows that the effects are transgenerational, underlined by the principles of genomic instability, and varied from one species to another. To further expand on the responses of and their sensitivity in different taxonomically distinct groups, the present study sought to reconstruct historic radiation doses and delineate their effects on bank voles (Clethrionomys glareolus) found within a 400-km radius of the Chernobyl Nuclear Power Plant meltdown site. Historic dose reconstruction from the whole-body dose rates for the bank vole samples for their parental generation at the time of radioactive release was performed. Relationships between the historic doses and cytogenetic aberrations and embryonic lethality were examined via graphical presentations. Results suggest that genomic instability develops at the historic dose range of 20–51 mGy while a radioadaptive response develops at the historic dose range of 51–356 mGy. The Linear No-Threshold (LNT) relationship was absent at historic doses of lower than 356 mGy at all generations. However, LNT was apparent when the very high historic dose of 10.28 Gy in one sampling year was factored into the dose response curve for the bank vole generation 21–22. It is worth being reminded that natural mutation accumulation and other environmental stressors outside the realm of dose effects could contribute to the observed effects in a multiple-stressor environment. Nevertheless, the consistent development of genomic instability and radio-adaptive response across generations and sampling sites unearths the utmost fundamental radiobiological principle of transgenerational non-targeted effects. As a result, it calls for better attention and regulation from global governing bodies of environmental health protection.

Studies of radiation health effects inform EPA actions

In 1970, the US Environmental Protection Agency (EPA) was given the responsibility to provide guidance to other federal agencies in the formulation of radiation protection standards. To carry out its federal guidance responsibilities and protect human health, the EPA must estimate risk at low doses to limit the risk of radiogenic cancers from environmental exposures. These risk estimates are based on models which conform to the linear no threshold (LNT) hypothesis. A cancer risk model conforms to the LNT hypothesis if the excess risk of cancer at low doses increases approximately proportional to dose, with no threshold. Risk models with a linear-quadratic dose response can satisfy the LNT hypothesis. Based on careful review of evidence from epidemiological and radiobiological studies, authoritative scientific bodies have repeatedly endorsed the use of LNT models for estimating and regulating risk and concluded that despite uncertainties at low dose and dose rates, the LNT model remains the most practical and implementable model for radiation protection. This article describes the rationale underlying the use of LNT models for calculating risk for low dose and dose rate exposures and discusses some of the epidemiological evidence which inform on its continued use.

Let's Get Real about Molecular Breast Imaging and Radiation Risk.

Let's Get Real about Molecular Breast Imaging and Radiation Risk.

Considerations for the Use of Mutation as a Regulatory Endpoint in Risk Assessment.

Assessment of a chemical's potential to cause permanent changes in the genetic code has been a common practice in the industry and regulatory settings for decades. Furthermore, the genetic toxicity battery of tests has typically been employed during the earliest stages of the research and development programs of new product development. A positive outcome from such battery has a major impact on the chemical's utility, industrial hygiene, product stewardship practices, and product life cycle analysis, among many other decisions that need to be taken by the industry, even before the registration of a chemical is undertaken. Under the prevailing regulatory paradigm, the dichotomous (yes/no) evaluation of the chemical's genotoxic potential leads to a conservative, linear no-threshold (LNT) risk assessment, unless compelling and undeniable data to the contrary can be provided to satisfy regulators, typically in a number of different global jurisdictions. With the current advent of predictive methods, new testing paradigms, mode-of-action/adverse outcome pathways, and quantitative risk assessment approaches, various stakeholders are starting to employ these state-of-the-science methodologies to further the conversation on decision making and advance the regulatory paradigm beyond the dominant LNT status quo. This commentary describes these novel methodologies, relevant biological responses, and how these can affect internal and regulatory risk assessment approaches. Environ. Mol. Mutagen. 61:84-93, 2020. © 2019 Wiley Periodicals, Inc.

INF/IL-4 increases after the low doses of gamma radiation in BALB/c spleen lymphocytes

Introduction: The effects of the low dose of ionizing radiation are not thoroughly evident due to an unavoidable increase of occupational exposure and the widespread application of ionizing radiation in medical and industrial fields. The aim of this study was to investigate immune system responses following the low doses of ionizing radiation. Material and Methods: BALB/c mice were exposed to Whole Body Irradiation of 20, 50, and 100 mGy through a 60Co source. Lymphocytes extraction were operated 24 h after irradiation. Afterwards, gene expression analysis was performed with relative quantitative Real-Time polymerase chain reaction to IL-4, IFN-γ, and TGF-β expression levels. Moreover, IFN-γ/IL-4 ratio was computed, and the independent sample t-test was performed for the statistical analysis. Results: Whereas IL-4, IFN-γ, and TGF-β expression levels decrease after the radiation of the low doses of gamma rays, the IFN-γ/IL-4 ratio increased significantly after irradiation of 20 mGy (P-Value<0.05). However, this ratio did not vary following the gamma irradiation of 50 and 100 mGy. Conclusion: The positive effects of the low dose of ionizing radiation can be observed through significant alterations in gene expression and the activation of protection mechanisms. This process was caused by the modulation of cellular immune responses after the exposure to 20 mGy. Although the irradiation of higher doses (50 and 100 mGy) induced alterations in the IFN- γ/IL-4 ratio was insignificant. These findings did not confirm the linear no-threshold model theory, and demonstrated that the low dose of ionizing radiation could be the cause of the hormesis phenomenon.

What Can Chemical Carcinogenesis Shed Light on the LNT Hypothesis in Radiation Carcinogenesis?

To protect the public’s health from exposure to physical, chemical, and microbiological agents, it is important that any policy be based on rigorous scientifically based research. The concept of “linear no-threshold” (LNT) has been implemented to provide guideline exposures to these agents. The practical limitation to testing this hypothesis is to provide sufficient samples for experimental or epidemiological studies. While there is no universally accepted understanding of most human diseases, there seems to be better understanding of cancer that might help resolve the “LNT” model. The public’s concern, after being exposed to radiation, is the potential of producing cancer. The most rigorous hypothesis of human carcinogenesis is the “multistage, multimechanism” chemical carcinogenesis model. The radiation carcinogenesis LNT model, rarely, if ever, built it into their support. It will be argued that this multistage, multimechanism model of carcinogenesis, involving the “initiation” of a single cell by a mutagen event, followed by chronic exposure to threshold levels of epigenetic agents or conditions that stimulate the clonal expansion of the “initiated” cell, can convert these benign cells to become invasive and metastatic. This “promotion” process can be interrupted, thereby preventing these initiated cells from transitioning to the “progression” process of invasion and metastasis.

Evaluation of the Risks and Benefits of Computed Tomography Urography for Assessment of Gross Hematuria

ObjectiveTo model the risk of radiation-induced malignancy from computed tomography urography (CTU) in evaluation of gross hematuria and contrast this with the benefits of urinary tract cancer detection when compared to renal ultrasound. MethodsA PUBMED-based literature search was performed to identify model inputs. Estimates of radiation-induced malignancy rates were obtained from the Biological Effects of Ionizing Radiation VII report with dose extrapolation using the linear no-threshold model. ResultsMale gender and age over 50 years were associated with a relative risk of upper tract malignancy of 2.04 and 2.95, respectively. The risk of upper tract malignancy missed by renal ultrasound ranged from 0.055% in females under 50 to 0.51% in males over 50. Risk of CTU-induced malignancy with associated loss of life expectancy ranged from 0.25% and 0.027 years in females under 50 to 0.08% and 0.0054 years in males over 50. For CTU to be superior to renal ultrasound, an undiagnosed upper tract malignancy would have to carry a loss of life expectancy of 49.2 years in females under 50, 13.4 years in males under 50, 2.6 years in females over 50, and 1.1 years in males over 50. ConclusionIn low-risk patients, CTU for evaluation of gross hematuria may carry a significant risk of radiation-induced secondary malignancy relative to the diagnostic benefit offered over renal ultrasound

Linear No-threshold (LNT) vs. Hormesis: Paradigms, Assumptions, and Mathematical Conventions that Bias the Conclusions in Favor of LNT and Against hormesis.

The linear no-threshold assumption misunderstands the complex multiphasic biological response to ionizing radiation, focusing solely on the initial physical radiogenic damage. This misunderstanding is enabled (masked and amplified) by a number of mathematical approaches that bias results in favor of linear no-threshold and away from alternatives, like hormesis, that take biological response into account. Here we explore a number of these mathematical approaches in some detail, including the use of frequentist rather than Bayesian statistical rules and methods. We argue that a Bayesian approach cuts through an epidemiological stalemate, in part because it enables a better understanding of the concept of plausibility, which in turn properly rests on empirical evidence of actual physical and biological mechanisms. Misuse of the concept of plausibility has sometimes been used to justify the mathematically simple and convenient linearity-without-a-threshold assumption, in particular with the everywhere-positive slope that is central to linear no-threshold and its variants. Linear no-threshold's dominance in the area of dose regulation further rests on a misapplication of the precautionary principle, which only holds when a putative caution has positive effects that outweigh the negative unintended consequences. In this case the negative consequences far outweigh the presumed hazards.

Martian Residents: Mass Media and Ramsar High Background Radiation Areas.

Considering current controversies regarding the health effects of low doses of ionizing radiation, study of the high background radiation areas such as Ramsar, Iran can help scientists better evaluate the validity of linear no-threshold (LNT) hypothesis. Ramsar is a coastal city in northern Iran with some areas known to have the highest levels of natural background radiation in the world. The mean annual dose of the residents of high background radiation areas (HBRAs) of Ramsar is 10 times higher than the public dose limit recommended by the ICRP (1 mSv/year) and a proportion of the residents receive annual doses as large as 260 mSv (13 times higher than the occupational dose limit recommended by the ICRP). A report published in Popular Science proclaims that background radiation in Ramsar approaches that of the Martian surface. However, estimates show that the maximum annual radiation dose in HBRAs of Ramsar can be much higher than that of the Martian surface (260 mGy/y vs 76 mGy/y). Furthermore, a Guardian report introduces Talesh Mahalleh, a district in Ramsar, as an inhabited area with the highest levels of natural radioactivity in the world and C Net claims that the best Mars colonists may come from places like Iran and Brazil. In spite of current concerns, nearly all residents still live in their paternal dwellings and there are not consistent reports on any detrimental effects. It is worth noting that, due to small sample size, to draw a firm conclusion about the health effects of high level natural radiation in Ramsar, in particular about the cancer risk, current information is not sufficient and further studies are needed.

UNIVERSAL RADIATION PROTECTION SYSTEM (URPS); A NATURAL GLOBAL STANDARDISED TREND FOR HUMAN EXPOSURE CONTROL IN 21st CENTURY.

In order to address the many deficiencies with current radiological protection system worldwide, this paper proposes a new Universal Radiation Protection System (URPS) Hypothesis with novel philosophy, concepts and methodologies of applying principles of equal human health-effect risks of an individual per unit radiation dose either from environmental natural background (NBG) or man-made sources; a 'standardised integrated dose system' for integrating all individual doses with emphasis on national NBG doses; considering worker as a member of public; and a 'cause-effect conservation principle' for epidemiology risk estimation. The URPS also a radiation hypothesises fractionation weighting factors (WF); a 'URPS Model' for bridging 'linear no-threshold and hormesis models'; example dose limit for workers; as well as new terms and definitions. State-of-the-art developments on URPS hypothesis are presented and discussed with simple global natural trends for standardised human exposure control in order to protect workers, patients, public and environment by standardised methods independent of source and country of origin in the 21st century.

To Mitigate The Lnt Model's Unintended Consequences-A Proposed Stopping Point For As Low As Reasonably Achievable.

While the debate over the linear no-threshold model continues, there's a relatively straightforward step that can be taken to mitigate the unintended consequences of the linear no-threshold model and the application of the as low as reasonably achievable principle-enact a stopping point for as low as reasonably achievable. The National Council on Radiation Protection and Measurements defined the negligible individual dose in 1993 as having a value of 0.01 mSv y. Radiation safety professionals overwhelmingly agree that applying the as low as reasonably achievable principle at very low doses, such as those consistent with background radiation levels, is not improving radiation safety of the public or radiation workers. To the contrary, this practice has significant financial and social consequences, and it severely inhibits public communication of radiation risks. To move forward, the National Council on Radiation Protection and Measurements should increase the negligible individual dose to a more practical value of 0.1 mSv y-the new as low as reasonably achievable stopping point. While radiation research in radiation biology and epidemiology are needed to better understand low-dose health effects below 100 mSv, in the meantime we should apply what we know-i.e., that radiation protection should not include trying to protect people from radiation doses that are consistent with variations in background radiation.

A Critical Assessment of the Linear No-Threshold Hypothesis: Its Validity and Applicability for Use in Risk Assessment and Radiation Protection.

The Society of Nuclear Medicine and Molecular Imaging convened a task group to examine the evidence for the risk of carcinogenesis from low-dose radiation exposure and to assess evidence in the scientific literature related to the overall validity of the linear no-threshold (LNT) hypothesis and its applicability for use in risk assessment and radiation protection. In the low-dose and dose-rate region, the group concluded that the LNT hypothesis is invalid as it is not supported by the available scientific evidence and, instead, is actually refuted by published epidemiology and radiation biology. The task group concluded that the evidence does not support the use of LNT either for risk assessment or radiation protection in the low-dose and dose-rate region.

A Critical Assessment of the Linear No-Threshold Hypothesis: What Is the Evidence?

The Linear No-Threshold (LNT) hypothesis regarding low-level radiation is based on expert opinion. As more experts critically evaluate the absence of convincing evidence supporting the LNT hypothesis, the more likely we will recognize that LNT may create more risk than it mitigates.

Modeling the Incidence of Secondary Malignancy Related to Ionizing Radiation Use in the Management of Nephrolithiasis

ObjectiveTo model the risk of secondary malignancy and associated mortality due to ionizing radiation from the evaluation and management of nephrolithiasis. MethodsA PUBMED-based literature search was performed to identify model inputs, specifically annual incidence of nephrolithiasis sub-stratified by age and gender and radiation exposure associated with nephrolithiasis episodes. Estimates of age and gender specific radiation-induced malignancy and mortality rates were obtained from the BEIR VII Phase 2 report with dose extrapolation using the linear no-threshold model. ResultsIncidence of new diagnoses of nephrolithiasis ranged from 42/100,000 in males 20-30 years old to 248/100,000 in males 60-70 years old. Radiation exposure per nephrolithiasis episode was 37.3 mSv over a 2-year period. Data regarding average stone episodes per patient with nephrolithiasis was limited and conservatively estimated at 1.5. Modeled lifetime attributable risk of secondary malignancy and subsequent mortality in individual stone patients ranged from 0.096% and 0.085%, respectively, in males over the age of 70 to 0.59% and 0.39% in females 20-30 years old. In the USA, overall incidence of secondary malignancy and associated mortality related to nephrolithiasis management was calculated to be 862.7 and 545.3 cases/year, respectively. ConclusionThis model suggests that ionizing radiation from the management of nephrolithiasis carries a small but significant risk of causing secondary malignancy. This knowledge must be considered when using modalities that involve radiation in the diagnosis and therapeutic management of nephrolithiasis.

Inflammation as a Cancer Co-Initiator: New Mechanistic Model Predicts Low/Negligible Risk at Noninflammatory Carcinogen Doses.

Linear-no-threshold (LNT) risk extrapolation has long been applied to estimate risks posed by low-level environmental carcinogen exposures, based on the 60-year-old multistage somatic mutation/clonal expansion (MSM) cancer theory. Recent evidence supports an alternative theory: Malignant tumors arise most efficiently from a stem cell that incurs requisite mutations and also is activated by inflammation to an epigenetically mediated and maintained state of adaptive hyperplasia (AH). This new inflammation-MSM (ISM) theory posits that inflammation-activated stem cells normally restricted to sites of injury-induced inflammation and tissue repair become uniquely susceptible to efficient carcinogenesis if normal post-inflammation AH termination is blocked by mutation. This theory posits that inflammation generally thus co-initiates cancer and transiently amplifies activated stem cells, implying that MSM theory (eg, the 2-stage stochastic “Moolgavkar, Venzon, Knudson [MVK]” model) is incomplete. Because inflammation dose–response typically is not LNT, the ISM theory predicts this is also true for most (perhaps all) carcinogens. The ISM (but not the MVK) model is shown to be consistent with recent data showing ∼100% carcinoma incidence (but not DNA adducts) in livers of rats exposed to aflatoxin B1 and was eliminated when that dose was co-administered with a highly potent anti-inflammatory agent. Experimental approaches to test ISM theory more robustly are discussed.

The Scoliosis Quandary: Are Radiation Exposures From Repeated X-Rays Harmful?

X-rays have been the gold standard for diagnosis, evaluation, and management of spinal scoliosis for decades as other assessment methods are indirect, too expensive, or not practical in practice. The average scoliosis patient will receive 10 to 25 spinal X-rays over several years equating to a maximum estimated dose of 10 to 25 mGy. Some patients, those getting diagnosed at a younger age and receiving early and ongoing treatments, may receive up to 40 to 50 X-rays, approaching at most 50 mGy. There are concerns that repeated radiographs given to patients are carcinogenic. Some studies have used the linear no-threshold model to derive cancer-risk estimates; however, it is invalid for low-dose irradiation (ie, X-rays); these estimates are untrue. Other studies have calculated cancer-risk ratios from long-term health data of historic scoliosis cohorts. Since data indicate reduced cancer rates in a cohort receiving a total radiation dose between 50 and 300 mGy, it is unlikely that scoliosis patients would get cancer from repeated X-rays. Moreover, since the threshold for leukemia is about 1100 mGy, scoliosis patients will not likely develop cancers from spinal X-rays. Scoliosis patients likely have long-term health consequences, including cancers, from the actual disease entity itself and not from protracted X-ray radiation exposures that are essential and indeed safe.