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BEIR VII develops the most up-to-date and comprehensive risk estimates for cancer and other health effects from exposure to low-level ionizing radiation. It is among the first reports of its kind to include detailed estimates for cancer incidence in addition to cancer mortality. In general, BEIR VII supports previously reported risk estimates for cancer and leukemia, but the availability of new and more extensive data have strengthened confidence in these estimates. A comprehensive review of available biological and biophysical data supports a \"linear-no-threshold\" (LNT) risk model-that the risk of cancer proceeds in a linear fashion at lower doses without a threshold and that the smallest dose has the potential to cause a small increase in risk to humans. The report is from the Board on Radiation Research Effects that is now part of the newly formed Nuclear and Radiation Studies Board.

This volume is part of the ongoing review of the underlying scientific bases for decision-making in chemical risk assessment by International Programme on Chemical Safety. It involves specific consideration of the area of dose-response assessment in the evaluation of information from toxicological studies in animals and from human clinical and epidemiological studies. It covers toxicants with threshold effects and those for which there may be no practical threshold, such as substances that are genotoxic and carcinogenic. The discussions are concerned with that subset of cause-effect relationships commonly referred to as dose-response models, which are typically used to characterize the biological effects of intentional (e.g. drugs and nutrients) and unintentional (e.g. contaminants) exposure to chemicals.This report is intended primarily to provide descriptive guidance for risk assessors in using dose-response modelling in hazard characterization. It will also provide mathematical modellers with an appreciation of issues to be considered when modelling in the context of the risk assessment process. Risk managers will be able to obtain a general understanding of the applications and limitations of dose-response modelling. For both risk assessors and risk managers, some considerations for communicating the results of risk assessments that use dose-response modelling are presented.

The anti–interleukin-1 antibody canakinumab was effective at controlling and preventing recurrence of flares in autoimmune inflammatory diseases: familial Mediterranean fever, mevalonate kinase deficiency, and the TNF receptor–associated periodic syndrome.

Risk assessment has become a dominant public policy tool for making choices, based on limited resources, to protect public health and the environment. It has been instrumental to the mission of the U.S. Environmental Protection Agency (EPA) as well as other federal agencies in evaluating public health concerns, informing regulatory and technological decisions, prioritizing research needs and funding, and in developing approaches for cost-benefit analysis. However, risk assessment is at a crossroads. Despite advances in the field, risk assessment faces a number of significant challenges including lengthy delays in making complex decisions; lack of data leading to significant uncertainty in risk assessments; and many chemicals in the marketplace that have not been evaluated and emerging agents requiring assessment. Science and Decisions makes practical scientific and technical recommendations to address these challenges. This book is a complement to the widely used 1983 National Academies book, Risk Assessment in the Federal Government (also known as the Red Book). The earlier book established a framework for the concepts and conduct of risk assessment that has been adopted by numerous expert committees, regulatory agencies, and public health institutions. The new book embeds these concepts within a broader framework for risk-based decision-making. Together, these are essential references for those working in the regulatory and public health fields.

Paediatric dose cannot be scaled down directly from an adult using weight (eg, mg/kg). This results in a dose too small in infants and children because elimination does not change in direct proportion to weight, and a dose too large in neonates whose drug elimination pathways are immature. The goal of treatment is a desired response (the target effect). An understanding of the concentration–response relationship (pharmacodynamics) can be used to predict the target concentration required to achieve this target effect. Pharmacokinetic knowledge then determines the target dose that will achieve the target concentration. Variability associated with both pharmacokinetics and pharmacodynamics can be reduced by demographic information (covariates), which can be used to help predict the target dose in a specific child. The covariates of size, maturation and organ function are the three principle contributors to pharmacokinetic variability. Children (2 years postnatal age or older) are essentially similar to adults (ie, mature) and differ only in size. Maturation processes are only important in neonates and infants, therefore, this cohort can be viewed as immature children. Paediatric pharmacodynamic studies are fewer than pharmacokinetic studies, but are required to elucidate the target concentration and consequent dose. The lack of pharmacodynamic studies is a serious challenge for rational dosing.

Background: Current knowledge about Chornobyl-related thyroid cancer risks comes from ecological studies based on grouped doses, case-control studies, and studies of prevalent cancers. Objective: To address this limitation, we evaluated the dose-response relationship for incident thyroid cancers using measurement-based individual iodine-131 (1-131) thyroid dose estimates in a prospective analytic cohort study. Methods: The cohort consists of individuals < 18 years of age on 26 April 1986 who resided in three contaminated oblasts (states) of Ukraine and underwent up to four thyroid screening examinations between 1998 and 2007 (n = 12,514). Thyroid doses of 1-131 were estimated based on individual radioactivity measurements taken within 2 months after the accident, environmental transport models, and interview data. Excess radiation risks were estimated using Poisson regression models. Results: Sixty-five incident thyroid cancers were diagnosed during the second through fourth screenings and 73,004 person-years (PY) of observation. The dose-response relationship was consistent with linearity on relative and absolute scales, although the excess relative risk (ERR) model described data better than did the excess absolute risk (EAR) model. The ERR per gray was 1.91 [95% confidence interval (CI), 0.43-6.34], and the EAR per 10⁴ PY/Gy was 2.21 (95% CI, 0.04-5.78). The ERR per gray varied significantly by oblast of residence but not by time since exposure, use of iodine prophylaxis, iodine status, sex, age, or tumor size. Conclusions: I-131-related thyroid cancer risks persisted for two decades after exposure, with no evidence of decrease during the observation period. The radiation risks, although smaller, are compatible with those of retrospective and ecological post-Chornobyl studies.

Previous studies have indicated that thyroid cancer risk after a first childhood malignancy is curvilinear with radiation dose, increasing at low to moderate doses and decreasing at high doses. Understanding factors that modify the radiation dose response over the entire therapeutic dose range is challenging and requires large numbers of subjects. We quantified the long-term risk of thyroid cancer associated with radiation treatment among 12,547 5-year survivors of a childhood cancer (leukemia, Hodgkin lymphoma and non-Hodgkin lymphoma, central nervous system cancer, soft tissue sarcoma, kidney cancer, bone cancer, neuroblastoma) diagnosed between 1970 and 1986 in the Childhood Cancer Survivor Study using the most current cohort follow-up to 2005. There were 119 subsequent pathologically confirmed thyroid cancer cases, and individual radiation doses to the thyroid gland were estimated for the entire cohort. This cohort study builds on the previous case-control study in this population (69 thyroid cancer cases with follow-up to 2000) by allowing the evaluation of both relative and absolute risks. Poisson regression analyses were used to calculate standardized incidence ratios (SIR), excess relative risks (ERR) and excess absolute risks (EAR) of thyroid cancer associated with radiation dose. Other factors such as sex, type of first cancer, attained age, age at exposure to radiation, time since exposure to radiation, and chemotherapy (yes/no) were assessed for their effect on the linear and exponential quadratic terms describing the dose–response relationship. Similar to the previous analysis, thyroid cancer risk increased linearly with radiation dose up to approximately 20 Gy, where the relative risk peaked at 14.6-fold (95% CI, 6.8–31.5). At thyroid radiation doses >20 Gy, a downturn in the dose–response relationship was observed. The ERR model that best fit the data was linear-exponential quadratic. We found that age at exposure modified the ERR linear dose term (higher radiation risk with younger age) (P < 0.001) and that sex (higher radiation risk among females) (P  =  0.008) and time since exposure (higher radiation risk with longer time) (P < 0.001) modified the EAR linear dose term. None of these factors modified the exponential quadratic (high dose) term. Sex, age at exposure and time since exposure were found to be significant modifiers of the radiation-related risk of thyroid cancer and as such are important factors to account for in clinical follow-up and thyroid cancer risk estimation among childhood cancer survivors.

This article explores the origin of the linear no-threshold (LNT) dose-response model and how it came to be used in cancer risk assessment worldwide. Following this historical appraisal is an evaluation of the LNT model, within the framework of the BEIR VII report of the National Academy of Sciences, on the health effects of ionizing radiation. The final section of this article provides an assessment of the LNT model's capacity to make accurate predictions of risk in the low-dose zone based on recent molecular mechanistic findings and epidemiological methods, with particular emphasis on the limitations of epidemiological studies to estimate risks in the low-dose zone.

High doses of ionizing radiation clearly produce deleterious consequences in humans, including, but not exclusively, cancer induction. At very low radiation doses the situation is much less clear, but the risks of low-dose radiation are of societal importance in relation to issues as varied as screening tests for cancer, the future of nuclear power, occupational radiation exposure, frequent-flyer risks, manned space exploration, and radiological terrorism. We review the difficulties involved in quantifying the risks of low-dose radiation and address two specific questions. First, what is the lowest dose of x- or γ-radiation for which good evidence exists of increased cancer risks in humans? The epidemiological data suggest that it is ≈10-50 mSv for an acute exposure and ≈50-100 mSv for a protracted exposure. Second, what is the most appropriate way to extrapolate such cancer risk estimates to still lower doses? Given that it is supported by experimentally grounded, quantifiable, biophysical arguments, a linear extrapolation of cancer risks from intermediate to very low doses currently appears to be the most appropriate methodology. This linearity assumption is not necessarily the most conservative approach, and it is likely that it will result in an underestimate of some radiation-induced cancer risks and an overestimate of others.

Objective This study aimed to establish the dose-response relationship between volume base dose and tumor local control for vaginal cancer, including primary vaginal cancer and recurrent gynecologic malignancies in the vagina. Materials and methods We identified studies that reported volume base dose and local control by searching the PubMed, the Web of Science, and the Cochrane Library Database through August 12, 2023. The regression analyses were performed using probit model between volume based dose versus clinical outcomes. Subgroup analyses were performed according to stratification: publication year, country, inclusion time of patients, patients with prior radiotherapy, age, primaries or recurrent, tumor size, concurrent chemoradiotherapy proportion, dose rate, image modality for planning, and interstitial proportion. Results A total of 879 patients with vaginal cancer were identified from 18 studies. Among them, 293 cases were primary vaginal cancer, 573 cases were recurrent cancer in the vagina, and 13 cases were unknown. The probit model showed a significant relationship between the HR-CTV (or CTV) D90 versus the 2-year and 3-year local control, P values were 0.013 and 0.014, respectively. The D90 corresponding to probabilities of 90% 2-year local control were 79.0 Gy EQD2,10 (95% CI: 75.3–96.6 Gy EQD2,10 ). Conclusions A significant dependence of 2-year or 3-year local control on HR-CTV (or CTV) D90 was found. Our research findings encourage further validation of the dose-response relationship of radical radiotherapy for vaginal cancer through protocol based multicenter clinical trials.