Ashley Pedigo Golden

Releases from nuclear or radiological security events can result in significant internal radiation contamination through inhalation of particulate contaminants. The International Commission on Radiological Protection (ICRP) has developed the reference Human Respiratory Tract Model (HRTM), detailed in ICRP Publications 66 and updated in the ICRP Publication 130, to estimate the deposition and clearance of inhaled radionuclides. Biokinetic models further estimate retention and excretion of internalized particulates, aiding the derivation of inhalation dose coefficients (DC). The HRTM developed by the ICRP utilizes deterministic quantities outlined in the ICRP Publication 66 and 130. The overarching goal of this study was to determine the variability from deterministic biokinetic/dosimetry models to represent the stochastic breadth of radionuclide metabolism in an exposed occupational population from realistic source terms, yielding an expanded compendium of inhalation dose coefficients. The analysis was carried out in three phases: (1) Development of an enhanced biokinetic and dose coefficient model and computational module based on ICRP Publication 130 HRTM and associated element specific systemic biokinetics; (2) Investigation of uncertain parameters in the HRTM; and (3) Stochastic analysis using Latin Hypercube Sampling, incorporating non-parametric (Kolmogorov-Smirnov statistics) test and Q-Q plots, informing parametric method, to characterize the distribution of the committed effective dose coefficients. To determine the most impactful parameters among the uncertain parameters, a Random Forest regression model was employed for feature importance, coupled with SHapley Additive exPlanations (SHAP) for comprehensive machine learning interpretation of the features. This study presents a unique stochastic framework for modeling inhaled particulate metabolism, enhancing capabilities in radiation consequence management, medical countermeasure development, and radiation dose reconstruction for epidemiological investigations.

Background: The Rocky Flats (RF) Plant operated from 1951-1989 as part of the U.S. Department of Energy (DOE) nuclear complex. Its primary mission was weapons component fabrication, whereby workers were potentially exposed to radioactive and non-radioactive hazards. RF worker mortality was compared to the general population, and dose-response relationships between mortality and radiation organ doses were examined. Methods: RF workers first employed between 1951 through 1979 for ≥30 days were identified (n=9,397). Vital status was determined using national and state death records through 2017. Organ doses from external photons and neutrons irridation and internalized plutonium, americium, and uranium were modeled as cumulative lagged total dose per year. Beryllium exposure was evaluated as an effect modifier using data from the DOE Nationwide Beryllium Medical Program. Statistical analyses included standardized mortality ratios (SMRs), Cox proportional hazard models, and excess relative risk (ERR) models. Results: Approximately 53.2% were deceased by the end of study. Nearly 90% were monitored for radiation exposure, with mean weighted absorbed dose of 59.0 mGy for lung. Nearly 45% of workers had intakes of alpha-particle emitting radionuclides, and 46.7% were monitored for neutrons. Leading causes of death included ischemic heart disease (n=999) and lung cancer (n=361). The highest SMRs were observed for berylliosis (SMR: 176.9; 95% CI: 76.2, 348.7; n<10) and asbestosis (SMR: 4.65; 95% CI: 2.23, 8.55;n=10). Dose-response analyses showed no statistical increase in risk from low-dose radiation including lung cancer (ERR per 100 mGy: -0.02; 95% CI: -0.11, 0.08; n=361) and Parkinson’s disease (ERR per 100 mGy: 0.13; 95% CI: -0.26, 0.31; n=57). Approximately 45% of workers were monitored for beryllium, with a weak non-significant indication of effect modification for lung cancer risk. Conclusion: The RF cohort showed no evidence of statistically significant increase in mortality from occupational radiation exposure. However, this study was limited by low statistical power, which inhibits the ability to detect effects. Future pooling of MPS cohorts will provide further insights, particularly regarding plutonium as a carcinogen.

The accurate reconstruction of external photon doses is essential for credible radiation epidemiology. This article presents the methodology used to derive dose estimates for 37 012 Hanford Site workers included in the Million Person Study. The approach employs historical dose records from the Hanford Radiation Exposure database and a previous epidemiology study. Bias correction factors specific to dosimeter type and period of use were applied and missing annual doses were estimated using a hierarchical nearby method to estimate deep dose equivalent for each worker. For early years with limited detection sensitivity, missed doses were quantified based on expected time-period-specific, low-dose statistical distributions. The revised dose estimates resulted in lower median and mean career doses than unadjusted data, while increasing the number of person-years with nonzero dose. Sensitivity analyses assessed the influence of bias in dosimetry measurements, missed doses and gap years on dose estimates. Differences in cumulative dose estimates between unadjusted and revised annual estimates are most prominent in the early operational years due to the highest bias during that time period.

The American radium dial worker (RDW) cohort of over 3200 persons is being revisited as part of the Million Person Study (MPS) to include a modern approach to RDW dosimetry. An exceptional source of data and contextualization in this project is an extensive collection of electronic records (digitized from existing microfilm and microfiche) housed at the United States Transuranium and Uranium Registries (USTUR). Although the type, extent, and quality (e.g. legibility) of record(s) varies between individuals, the remarkable occupational, medical and demographic data include in vivo radiation measurements (e.g. radon breath, whole body counts), autopsy results, medical records (including copies of radiographs), interviews over the years, and correspondence. Of particular dosimetric interest are the details of radiation measurements. For example, there are some instances where hand-written and transcribed values are both available, along with notes providing context for why a particular measurement in a series of measurements was chosen to assign an intake, or if there were concerns about a particular measurement. Born prior to 1935, RDW have nearly all passed away. Thus, the updated dosimetry, especially for the skeletal tissues, will allow the correlation of lifetime cumulative dose with radiation risk. Here we review typical information available in this collection of historical records and highlight some interesting finds. Additionally, we discuss the relevance to current and ongoing work related to updating the dosimetry of the RDW in the MPS, including providing an example of the usefulness of information contained in these records. The RDW cohort provides a unique historical perspective on occupational exposure to radium, making it a valuable dataset for understanding long-term health effects and improving current radiation protection standards.

Background: The aim of the Million Person Study of Low-Dose Health Effects (MPS) is to examine the level of radiation risk for chronic exposures received gradually over time and not acutely as was the case for the Japanese atomic bomb survivors. Nuclear power plant (NPP) workers comprise nearly 15 percent of the MPS. Leukemia, selected cancers, Parkinson’s disease, ischemic heart disease (IHD) and other causes of death are evaluated. Methods and material: The U.S. Nuclear Regulatory Commission’s Radiation Exposure Information and Reporting System (REIRS) and the Landauer, Inc. dosimetry databases identified 135,193 NPP workers first monitored 1957–1984. Annual personal dose equivalents [Hp(10)] were available for each worker. Radiation records from all places of employment were sought. Vital status was determined through 2011. Mean absorbed doses to red bone marrow (RBM), esophagus, lung, colon, brain and heart were estimated by adjusting the recorded Hp(10) for each worker by scaling factors, accounting for exposure geometry and energy of the incident gamma radiation. Standardized mortality ratios (SMR) were calculated. Radiation risks were estimated using Cox proportional hazards models. Results: Nearly 50% of workers were employed for more than 20 years. The mean duration of follow-up was 30.2 y. Overall, 29,124 total deaths occurred, 296 from leukemia other than chronic lymphocytic leukemia (CLL), 3382 from lung cancer, 140 from Parkinson’s disease and 5410 from IHD. The mean dose to RBM was 37.9 mGy (maximum 1.0 Gy; percent >100 mGy was 9.2%), 43.2 mGy to lung, 43.7 mGy to colon, 33.2 mGy to brain, and 43.9 mGy to heart. The SMRs (95% CI) were 1.06 (0.94; 1.19) for leukemia other than CLL, 1.10 (1.07; 1.14) for lung cancer, 0.90 (0.76; 1.06) for Parkinson’s disease, and 0.80 (0.78; 0.82) for IHD. The excess relative risk (ERR) per 100 mGy for leukemia other than CLL was 0.15 (90% CI −0.001; 0.31). For all solid cancers the ERR per 100 mGy (95% CI) was 0.01 (–0.03; 0.05), for lung cancer −0.04 (–0.11; 0.02), for Parkinson’s disease 0.24 (–0.02; 0.50), and for IHD −0.01 (–0.06; 0.04). Conclusion: Prolonged exposure to radiation increased the risk of leukemia other than CLL among NPP workers. There was little evidence for a radiation association for all solid cancers, lung cancer or ischemic heart disease. Increased precision will be forthcoming as the different cohorts within the MPS are combined, such as industrial radiographers and medical radiation workers who were assembled and evaluated in like manner.

Background: The study of Japanese atomic bomb survivors, exposed briefly to radiation, finds the risk of radiation-induced lung cancer to be nearly three times greater for women than for men. Because protection standards for astronauts are based on individual lifetime risk projections, this sex-specific difference limits the time women can spend in space. Populations exposed to chronic or fractionated radiation were evaluated to learn whether similar differences exist when exposures occur gradually over years. Methods and materials: Five occupational cohorts within the Million Person Study of Low-Dose Health Effects (MPS) and a Canadian Fluoroscopy Cohort Study (CFCS) of tuberculosis patients who underwent frequent chest fluoroscopic examinations are evaluated. Included are male and female workers at the Mound nuclear facility, nuclear power plants (NPP), and industrial radiographers (IR). Workers at the Mallinckrodt Chemical Works and military participants at aboveground nuclear weapons tests provide information on the risk among males. Cox proportional hazards and Poisson regression models were used to estimate sex-specific radiation risks for lung cancer and to compare any differences. Results: Overall, 15,065 lung cancers occurred among the 443,684 subjects studied: 50,111 women and 395,573 men. The mean cumulative dose to the lung was 166.3 mGy (range 6 to 1,055 mGy) with the highest among the TB-fluoroscopy patients (mean 1,055 mGy). Mean lung dose for women in the worker cohorts was generally 4 times lower than for men. Of the 12 estimates of radiation-related risk, only one, for male IRs, showed a significant elevation (ERR 0.09; 95% CI 0.02–0.16, at 100 mGy). In contrast, the dose response for male NPP workers was negative (ERR −0.05; 95% CI −0.10, 0.01, at 100 mGy). Combined, these two cohorts provided little evidence for a radiation effect among males (ERR 0.01; 95% CI −0.04, 0.06, at 100 mGy). There was no significant dose-response among females within any cohort. There was no difference in the sex-specific estimates of lung cancer risk. Conclusions: There was little evidence that chronic or fractionated exposures increased the risk of lung cancer. There were no differences in the risks of lung cancer between men and women. However, the sex-specific analyses are limited because of small numbers of women and relatively low doses. A more definitive study is ongoing of medical radiation workers which include 85,000 women and 85,000 men (overall mean dose 82 mGy, max 1,140 mGy). Additional understanding will come from the ongoing follow-up of the CFCS.

Purpose: To present how the Department of Energy’s (DOE) Comprehensive Epidemiologic Data Resource (CEDR) is integrated into the Million Person Study of Low Dose Health Effects (MPS). The history of DOE’s worker health surveillance and its epidemiology program are described. Methods and materials: A standard protocol is used to extract data from CEDR for use in the MPS. The data files are pulled from CEDR to form the basis for the cohort analyzed in the MPS. The previous study data are reviewed to formulate the protocol for the MPS study cohort. The activities needed to update the data to construct the new analytic files are carried out in parallel. The primary efforts relate to updating the vital status, retrieving cause of death information and calculating annual radiation doses for the specific organs of interest. Working data files containing the updated data are produced for construction of analytic data files used in the biostatistical analysis. At study completion the working and analytic data files are placed into CEDR for use by other researchers. Results: The use of CEDR to study the scientific and maintenance workers at the Los Alamos National Laboratory which is currently underway is used to demonstrate the process. Conclusions: There is a pressing need to answer the question of the health risk of exposure to chronic low-level exposure to ionizing radiation. Using CEDR as the starting point to identify new cohorts to include in the MPS is a cost-effective and a time efficient way to expedite answering this question.

Purpose: A substantial body of epidemiologic literature addresses risks associated with occupational radiation exposure but comparing results between studies is often difficult as different statistical models are commonly used. It is unclear whether different methods produce similar results for estimates of radiation risk when applied to the same data. The goal of this study was to compare the radiation risk estimates for leukemia other than chronic lymphocytic leukemia (non-CLL) and ischemic heart disease (IHD) produced by both Cox and Poisson regression models for time-dependent dose-response analyses of occupational exposure. Materials and methods: For brevity, this methods paper presents the results from one cohort, the Nuclear Power Plant workers (NPP), though the evaluation considered five cohorts of varying size and exposure as part of the Million Worker Study. Cox Proportional Hazards models, with age as the underlying timescale for hazard, were conducted using three computer software programs: SAS, R, and Epicure. Doses lagged 2 years for non-CLL and 10 years for ischemic heart disease were treated as time-dependent exposures at the annual level and were examined both in categories and as a continuous term. Hazard ratios (HR) and 95% confidence intervals (CI) were reported for each model in SAS and R, while the Peanuts program of Epicure was utilized to produce Excess Relative Risk (ERR) estimates and 95% CI. All models were adjusted for gender and year of birth. Four piece-wise exponential Poisson models (log-linear regression for rate) were developed with varying cutpoints for age strata from very fine to broad categories using both R and the Amfit program in Epicure for ERR estimates. Results: Comparable estimates of risk (both RR and ERR) were observed from Cox and Poisson models, regardless of software utilized, as long as appropriately narrow categories of age were utilized to control the confounding of age in Poisson models. The ERR estimates produced in Epicure tended to agree very closely with the HR or RR estimates, and the statistical software program used had no impact to risk estimates for the same model. Conclusions: As computational power is no longer the burden today as it has been in the past, the results of this evaluation support the use of the Cox proportional hazards or the ungrouped Poisson approach to analyzing time-dependent dose-response relationships to ensure that maximum control over the confounding of age is achieved in studies of mortality for cohorts occupationally exposed to radiation.

This book presents original research findings of The Million Person Study of Low-Dose Radiation Health Effects (MPS), the largest and most comprehensive epidemiologic study of its kind to investigate the health effects of low-level chronic radiation exposure on American workers and veterans throughout the 20th century. Since the early 1900s, epidemiologists have studied the consequences of radiation exposures, yet the health effects of low levels received gradually over time remain unresolved. This uncertainty comes at a time when the public and workers are experiencing ever-increasing levels of radiation exposure from advances in medical radiation imaging techniques (e.g., CT scans), frequent flying at high altitudes, and environmental and occupational exposures. The MPS is providing answers by studying 30 radiation-exposed U.S. populations, including workers at nuclear power plants, radiologists, workers at former Manhattan Project sites, nuclear submariners, nuclear weapons test participants (atomic veterans), industrial radiographers, and radium dial painters. Ongoing for more than 20 years and coordinated by the National Council on Radiation Protection and Measurements, Vanderbilt University Medical Center and Memorial Sloan Kettering Cancer Center, the MPS is a national effort supported by the Department of Energy, National Aeronautics and Space Administration, U.S. Navy, Defense Threat Reduction Agency, Nuclear Regulatory Commission, Centers for Disease Control and Prevention, and the Environmental Protection Agency. Unparalleled in scope and quality, the MPS provides an understanding of low-dose health effects that is desperately needed for decision-makers and the radiation protection community as society continues to increase the uses of radiation technologies. Individual chapters were originally published in the International Journal of Radiation Biology.

Background: Approximately 235,000 military personnel participated at one of 230 U.S. atmospheric nuclear weapons tests from 1945 through 1962. At the Nevada Test Site (NTS), the atomic veterans participated in military maneuvers, observed nuclear weapons tests, or provided technical support. At the Pacific Proving Ground (PPG), they served aboard ships or were stationed on islands during or after nuclear weapons tests. Material and methods: Participants at seven test series, previously studied with high-quality dosimetry and personnel records, and the first test at TRINITY formed the cohort of 114,270 male military participants traced for vital status from 1945 through 2010. Dose reconstructions were based on Nuclear Test Personnel Review records, Department of Defense. Standardized mortality ratios (SMR) and Cox and Poisson regression models were used in the analysis. Results: Most atomic veterans were enlisted men, served in the Navy at the PPG, and were born before 1930. Vital status was determined for 96.8% of the veterans; 60% had died. Enlisted men had significantly high all-causes mortality SMR (1.06); officers had significantly low all-causes mortality SMR (0.71). The pattern of risk over time showed a diminution of the ‘healthy soldier effect’: the all-causes mortality SMR after 50 years of follow-up was 1.00. The healthy soldier effect for all cancers also diminished over time. The all-cancer SMR was significantly high after 50 years (SMR 1.10) primarily from smoking-related cancers, attributed in part to the availability of cigarettes in military rations. The highest SMR was for mesothelioma (SMR 1.56) which was correlated with asbestos exposure in naval ships. Prostate cancer was significantly high (SMR 1.13). Ischemic heart disease was significantly low (SMR 0.84). Estimated mean doses varied by organ were low; e.g., the mean red bone marrow dose was 6 mGy (maximum 108 mGy). Internal cohort dose–response analyses provided no evidence for increasing trends with radiation dose for leukemia (excluding chronic lymphocytic leukemia (CLL)) [ERR (95% CI) per 100 mGy −0.37 (−1.08, 0.33); n = 710], CLL, myelodysplastic syndrome, multiple myeloma, ischemic heart disease, or cancers of the lung, prostate, breast, and brain. Conclusion: No statistically significant radiation associations were observed among 114,270 nuclear weapons test participants followed for up to 65 years. The 95% confidence limits were narrow and excluded mortality risks per unit dose that are two to four times higher than those reported in other investigations. Significantly elevated SMRs were seen for mesothelioma and asbestosis, attributed to asbestos exposure aboard ships.