Uncertainties in estimating health risks associated with exposure to ionising radiation.

The information for the present discussion on the uncertainties associated with estimation of radiation risks and probability of disease causation was assembled for the recently published NCRP Report No. 171 on this topic. This memorandum provides a timely overview of the topic, given that quantitative uncertainty analysis is the state of the art in health risk assessment and given its potential importance to developments in radiation protection. Over the past decade the increasing volume of epidemiology data and the supporting radiobiology findings have aided in the reduction of uncertainty in the risk estimates derived. However, it is equally apparent that there remain significant uncertainties related to dose assessment, low dose and low dose-rate extrapolation approaches (e.g. the selection of an appropriate dose and dose-rate effectiveness factor), the biological effectiveness where considerations of the health effects of high-LET and lower-energy low-LET radiations are required and the transfer of risks from a population for which health effects data are available to one for which such data are not available. The impact of radiation on human health has focused in recent years on cancer, although there has been a decided increase in the data for noncancer effects together with more reliable estimates of the risk following radiation exposure, even at relatively low doses (notably for cataracts and cardiovascular disease). New approaches for the estimation of hereditary risk have been developed with the use of human data whenever feasible, although the current estimates of heritable radiation effects still are based on mouse data because of an absence of effects in human studies. Uncertainties associated with estimation of these different types of health effects are discussed in a qualitative and semi-quantitative manner as appropriate. The way forward would seem to require additional epidemiological studies, especially studies of low dose and low dose-rate occupational and perhaps environmental exposures and for exposures to x rays and high-LET radiations used in medicine. The development of models for more reliably combining the epidemiology data with experimental laboratory animal and cellular data can enhance the overall risk assessment approach by providing biologically refined data to strengthen the estimation of effects at low doses as opposed to the sole use of mathematical models of epidemiological data that are primarily driven by medium/high doses. NASA's approach to radiation protection for astronauts, although a unique occupational group, indicates the possible applicability of estimates of risk and their uncertainty in a broader context for developing recommendations on: (1) dose limits for occupational exposure and exposure of members of the public; (2) criteria to limit exposures of workers and members of the public to radon and its short-lived decay products; and (3) the dosimetric quantity (effective dose) used in radiation protection.

Fluoroscopy X-Ray Organ-Specific Dosimetry System (FLUXOR) for Estimation of Organ Doses and Their Uncertainties in the Canadian Fluoroscopy Cohort Study.

As part of ongoing efforts to assess lifespan disease mortality and incidence in 63,715 patients from the Canadian Fluoroscopy Cohort Study (CFCS) who were treated for tuberculosis between 1930 and 1969, we developed a new FLUoroscopy X-ray ORgan-specific dosimetry system (FLUXOR) to estimate radiation doses to various organs and tissues. Approximately 45% of patients received medical procedures accompanied by fluoroscopy, including artificial pneumothorax (air in pleural cavity to collapse of lungs), pneumoperitoneum (air in peritoneal cavity), aspiration of fluid from pleural cavity and gastrointestinal series. In addition, patients received chest radiographs for purposes of diagnosis and monitoring of disease status. FLUXOR utilizes age-, sex- and body size-dependent dose coefficients for fluoroscopy and radiography exams, estimated using radiation transport simulations in up-to-date computational hybrid anthropomorphic phantoms. The phantoms include an updated heart model, and were adjusted to match the estimated mean height and body mass of tuberculosis patients in Canada during the relevant time period. Patient-specific data (machine settings, exposure duration, patient orientation) used during individual fluoroscopy or radiography exams were not recorded. Doses to patients were based on parameter values inferred from interviews with 91 physicians practicing at the time, historical literature, and estimated number of procedures from patient records. FLUXOR uses probability distributions to represent the uncertainty in the unknown true, average value of each dosimetry parameter. Uncertainties were shared across all patients within specific subgroups of the cohort, defined by age at treatment, sex, type of procedure, time period of exams and region (Nova Scotia or other provinces). Monte Carlo techniques were used to propagate uncertainties, by sampling alternative average values for each parameter. Alternative average doses per exam were estimated for patients in each subgroup, with the total average dose per individual determined by the number of exams received. This process was repeated to produce alternative cohort vectors of average organ doses per patient. This article presents estimates of doses to lungs, female breast, active bone marrow and heart wall. Means and 95% confidence intervals (CI) of average organ doses across all 63,715 patients were 320 (160, 560) mGy to lungs, 250 (120, 450) mGy to female breast, 190 (100, 340) mGy to heart wall and 92 (47, 160) mGy to active bone marrow. Approximately 60% of all patients had average doses to the four studied organs of less than 10 mGy, 10% received between 10 and 100 mGy, 25% between 100 and 1,000 mGy, and 5% above 1,000 mGy. Pneumothorax was the medical procedure that accounted for the largest contribution to cohort average doses. The major contributors to uncertainty in estimated doses per procedure for the four organs of interest are the uncertainties in exposure duration, tube voltage, tube output, and patient orientation relative to the X-ray tube, with the uncertainty in exposure duration being most often the dominant source. Uncertainty in patient orientation was important for doses to female breast, and, to a lesser degree, for doses to heart wall. The uncertainty in number of exams was an important contributor to uncertainty for ∼30% of patients. The estimated organ doses and their uncertainties will be used for analyses of incidence and mortality of cancer and non-cancer diseases. The CFCS cohort is an important addition to existing radio-epidemiological cohorts, given the moderate-to-high doses received fractionated over several years, the type of irradiation (external irradiation only), radiation type (X rays only), a balanced combination of both genders and inclusion of people of all ages.

Organ Doses from Chest Radiographs in Tuberculosis Patients in Canada and Their Uncertainties in Periods from 1930 to 1969.

This paper describes a study to estimate absorbed doses to various organs from film-based chest radiographs and their uncertainties in the periods 1930 to 1948, 1949 to 1955, and 1956 to 1969. Estimated organ doses will be used in new analyses of risks of cancer and other diseases in tuberculosis patients in Canada who had chest fluoroscopic and radiographic examinations in those periods. In this paper, doses to lungs, female breast, active bone marrow, and heart from a single chest radiograph in adults and children of ages 1, 5, 10, and 15 y in the Canadian cohort and their uncertainties are estimated using (1) data on the tube voltage (kV), total filtration (mm Al), tube-current exposure-time product (mA s), and tube output (mR [mA s]) in each period; (2) assumptions about patient orientation, distance from the source to the skin of a patient, and film size; and (3) new calculations of sex- and age-specific organ dose conversion coefficients (organ doses per dose in air at skin entrance). Variations in estimated doses to each organ across the three periods are less than 20% in adults and up to about 30% at younger ages. Uncertainties in estimated organ doses are about a factor of 2 to 3 in adults and up to a factor of 4 at younger ages and are due mainly to uncertainties in the tube voltage and tube-current exposure-time product.

NCRP Report 181, Evaluation of the Relative Effectiveness of Low-energy Photons and Electrons in Inducing Cancer in Humans: A Critique and Alternative Analysis.

A recent report from the National Council on Radiation Protection and Measurements presents an evaluation of the effectiveness of low-energy photons and electrons, relative to higher-energy photons, in inducing cancer in humans. The objective of that evaluation was to develop subjective probability distributions of an uncertain quantity, denoted by ρ, to represent ranges of credible values of the effectiveness of five groups of low-energy radiations (L): photons at about 1.5 keV; 15 to 30 keV photons; 40 to 60 keV photons; >60 to 150 keV photons; and electrons from beta decay of tritium (H). Probability distributions of ρL for all low-energy groups were derived based on an evaluation of uncertainties in data on biological effectiveness from five areas of research and use of an elicitation process and decomposition method to combine probability distributions to represent those uncertainties. In this paper, we argue that uncertainties in ρLs for all low-energy groups are too small compared with uncertainties in biological effectiveness from the different areas of research, especially that upper confidence limits of all ρLs are too low. These deflations of uncertainty in all ρLs apparently are due, at least in part, to an invalid assumption in the decomposition method that probability distributions of biological effectiveness from the different areas of research are representations of random uncertainty that arises from repeated measurements of the same quantity under the same conditions using well-calibrated instruments. However, those distributions essentially are representations of systematic uncertainty in different estimates of biological effectiveness from each area of research, which means that a deflation of uncertainty in ρLs is not a credible result. We then use the same probability distributions of biological effectiveness from the different areas of research in an alternative analysis to derive wider probability distributions of ρL that we believe provide a better representation of the state of knowledge of the effectiveness of low-energy photons and electrons in inducing cancer in humans. Our analysis is based on the notion that each probability distribution of biological effectiveness from an area of research represents a distinctly different model of a ρL and use of the concept of model averaging to combine those distributions.

Probability Distribution of Dose and Dose-Rate Effectiveness Factor for use in Estimating Risks of Solid Cancers From Exposure to Low-Let Radiation.

This paper presents an analysis to develop a subjective state-of-knowledge probability distribution of a dose and dose-rate effectiveness factor for use in estimating risks of solid cancers from exposure to low linear energy transfer radiation (photons or electrons) whenever linear dose responses from acute and chronic exposure are assumed. A dose and dose-rate effectiveness factor represents an assumption that the risk of a solid cancer per Gy at low acute doses or low dose rates of low linear energy transfer radiation, RL, differs from the risk per Gy at higher acute doses, RH; RL is estimated as RH divided by a dose and dose-rate effectiveness factor, where RH is estimated from analyses of dose responses in Japanese atomic-bomb survivors. A probability distribution to represent uncertainty in a dose and dose-rate effectiveness factor for solid cancers was developed from analyses of epidemiologic data on risks of incidence or mortality from all solid cancers as a group or all cancers excluding leukemias, including (1) analyses of possible nonlinearities in dose responses in atomic-bomb survivors, which give estimates of a low-dose effectiveness factor, and (2) comparisons of risks in radiation workers or members of the public from chronic exposure to low linear energy transfer radiation at low dose rates with risks in atomic-bomb survivors, which give estimates of a dose-rate effectiveness factor. Probability distributions of uncertain low-dose effectiveness factors and dose-rate effectiveness factors for solid cancer incidence and mortality were combined using assumptions about the relative weight that should be assigned to each estimate to represent its relevance to estimation of a dose and dose-rate effectiveness factor. The probability distribution of a dose and dose-rate effectiveness factor for solid cancers developed in this study has a median (50th percentile) and 90% subjective confidence interval of 1.3 (0.47, 3.6). The harmonic mean is 1.1, which implies that the arithmetic mean of an uncertain estimate of the risk of a solid cancer per Gy at low acute doses or low dose rates of low linear energy transfer radiation is only about 10% less than the mean risk per Gy at higher acute doses. Data were also evaluated to define a low acute dose or low dose rate of low linear energy transfer radiation, i.e., a dose or dose rate below which a dose and dose-rate effectiveness factor should be applied in estimating risks of solid cancers.

Derivation of a screening methodology for evaluating radiation dose to aquatic and terrestrial biota.

The United States Department of Energy (DOE) currently has in place a radiation dose standard for the protection of aquatic animals, and is considering additional dose standards for terrestrial biota. These standards are: 10 mGy/d for aquatic animals, 10 mGy/d for terrestrial plants, and, 1 mGy/d for terrestrial animals. Guidance on suitable approaches to the implementation of these standards is needed. A screening methodology, developed through DOE's Biota Dose Assessment Committee (BDAC), serves as the principal element of DOE's graded approach for evaluating radiation doses to aquatic and terrestrial biota. Limiting concentrations of radionuclides in water, soil, and sediment were derived for 23 radionuclides. Four organism types (aquatic animals; riparian animals; terrestrial animals; and terrestrial plants) were selected as the basis for development of the screening method. Internal doses for each organism type were calculated as the product of contaminant concentration, bioaccumulation factor(s) and dose conversion factors. External doses were calculated based on the assumption of immersion of the organism in soil, sediment, or water. The assumptions and default parameters used provide for conservative screening values. The screening methodology within DOE's graded approach should prove useful in demonstrating compliance with biota dose limits and for conducting screening assessments of radioecological impact. It provides a needed evaluation tool that can be employed within a framework for protection of the environment.

Beyond dose assessment: using risk with full disclosure of uncertainty in public and scientific communication.

Evaluations of radiation exposures of workers and the public traditionally focus on assessments of radiation dose, especially annual dose, without explicitly evaluating the health risk associated with those exposures, principally the risk of radiation-induced cancer. When dose is the endpoint of an assessment, opportunities to communicate the significance of exposures are limited to comparisons with dose criteria in regulations, doses due to natural background or medical x-rays, and doses above which a statistically significant increase of disease has been observed in epidemiologic studies. Risk assessment generally addresses the chance (probability) that specific diseases might be induced by past, present, or future exposure. The risk of cancer per unit dose will vary depending on gender, age, exposure type (acute or chronic), and radiation type. It is not uncommon to find that two individuals with the same effective dose will have substantially different risks. Risk assessment has shown, for example, that: (a) medical exposures to computed tomography scans have become a leading source of future risk to the general population, and that the risk would be increased above recently published estimates if the incidence of skin cancer and the increased risk from exposure to x-rays compared with high-energy photons were taken into account; (b) indoor radon is a significant contributor to the baseline risk of lung cancer, particularly among people who have never smoked; and (c) members of the public who were exposed in childhood to I in fallout from atmospheric nuclear weapons tests and were diagnosed with thyroid cancer later in life would frequently meet criteria established for federal compensation of cancers experienced by energy workers and military participants at atmospheric weapons tests. Risk estimation also enables comparisons of impacts of exposures to radiation and chemical carcinogens and other hazards to life and health. Communication of risk with uncertainty is essential for reaching informed consent, whether communicating to a larger community debating the tradeoffs of risks and benefits of an action that involves radiation exposure or communicating at the level of a physician and patient.

Interactive RadioEpidemiological Program (IREP): a web-based tool for estimating probability of causation/assigned share of radiogenic cancers.

The Interactive RadioEpidemiological Program (IREP) is a Web-based, interactive computer code that is used to estimate the probability that a given cancer in an individual was induced by given exposures to ionizing radiation. IREP was developed by a Working Group of the National Cancer Institute and Centers for Disease Control and Prevention, and was adopted and modified by the National Institute for Occupational Safety and Health (NIOSH) for use in adjudicating claims for compensation for cancer under the Energy Employees Occupational Illness Compensation Program Act of 2000. In this paper, the quantity calculated in IREP is referred to as "probability of causation/assigned share" (PC/AS). PC/AS for a given cancer in an individual is calculated on the basis of an estimate of the excess relative risk (ERR) associated with given radiation exposures and the relationship PC/AS = ERR/ERR+1. IREP accounts for uncertainties in calculating probability distributions of ERR and PC/AS. An accounting of uncertainty is necessary when decisions about granting claims for compensation for cancer are made on the basis of an estimate of the upper 99% credibility limit of PC/AS to give claimants the "benefit of the doubt." This paper discusses models and methods incorporated in IREP to estimate ERR and PC/AS. Approaches to accounting for uncertainty are emphasized, and limitations of IREP are discussed. Although IREP is intended to provide unbiased estimates of ERR and PC/AS and their uncertainties to represent the current state of knowledge, there are situations described in this paper in which NIOSH, as a matter of policy, makes assumptions that give a higher estimate of the upper 99% credibility limit of PC/AS than other plausible alternatives and, thus, are more favorable to claimants.