2024 IRPA16 HPS69 | U.S. Transuranium and Uranium Registries

^{U.S. Transuranium and Uranium Registries} _{Conference Contributions}

16^th International Radiation Protection Association (IRPA) International Congress, Orlando, FL, July 7-12, 2024

George Tabatadze, Xirui Liu, Stacey McComish, and Maia Avtandilashvili at the IRPA/HPS meeting. [Not pictured: Sergey Tolmachev and Daniel Strom]

Six members of the USTUR research team attended the 16^th International Congress of the International Radiation Protection Association (IRPA16) in Orlando, FL. They presented two platform presentations, four posters, one personal enrichment program (PEP) seminar, and were coauthors on an additional two platform and two poster presentations. IRPA16 was a joint meeting with the 69^th Annual Meeting of the Health Physics Society, and was well attended by radiation safety professionals from around the world.

Maia Avtandilashvili (USTUR), Elizabeth Thomas (USTUR), George Tabatadze (USTUR), Sergey Tolmachev (USTUR)

The United States Transuranium and Uranium Registries (USTUR) studies actinide biokinetics and tissue dosimetry by following up occupationally exposed workers. At the USTUR, postmortem tissue radiochemical analysis data are used to improve biokinetic models for radiological protection. For accurate assessment of radiation doses from intakes of plutonium, information on material type is important. In occupational settings, inhalation is the most common route of intake. In this study, activity concentrations of plutonium isotopes were measured in the lungs, thoracic lymph nodes (LNTH), liver, and skeleton from 291 former nuclear workers from Hanford (116 individuals), Los Alamos (40), and Rocky Flats (135). To characterize plutonium material type (solubility), the LNTH-to-lung activity concentration ratios and liver-to-respiratory tract activity ratios were calculated. Since smoking affects plutonium material transport in the respiratory tract, LNTH-to-lung ratios for smokers and non-smokers were compared. With limited data analyzed, a significant statistical difference in the LNTH-to-lung concentration ratios was observed among three sites (p = 0.0008) with median values of 21.1 (n = 108), 31.5 (n = 37), and 11.4 (n = 121) for Hanford, Los Alamos, and Rocky Flats, respectively. The LNTH-to-lung ratios were significantly different between smokers and non-smokers (p = 0.0066) with the corresponding median values of 19.7 (n = 156) and 41.8 (n = 41). Highly significant difference among three sites (p < 0.00001) was observed for the liver-to-respiratory tract activity ratios with median values of 3.25 (n = 99), 0.49 (n = 34), and 0.35 (n = 110) for Hanford, Los Alamos, and Rocky Flats, respectively, indicating that, among the three worksites, Hanford workers were exposed to the most soluble plutonium material. Information on plutonium material solubility can be used to improve worksite-specific dose assessment in support of radiation epidemiology. [USTUR-0662-23A]

Presentation slides

Sara Dumit (LANL), Maia Avtandilashvili (USTUR), Stacey McComish (USTUR), Guthrie Miller (retired LANL), Jasen Swanson (US Army), Sergey Tolmachev (USTUR)

The present work models plutonium (Pu) biokinetics in a female former nuclear worker. Her bioassay measurements are available at the U.S. Transuranium and Uranium Registries. The worker was internally exposed to a plutonium-americium mixture via acute inhalation at a nuclear weapons facility. She was medically treated with injections of 1 g Ca-DTPA on days 0, 5, and 14 after the intake. Between days 0 and 20, 13 fecal and 24 urine samples were collected and analyzed for ²³⁹Pu and americium (²⁴¹Am). Subsequently, she was followed-up for bioassay monitoring over 14 years, with 13 additional post-treatment urine samples collected and analyzed for Pu. The uniqueness of this dataset is due to the availability of: (i) both early and long-term bioassay data from a female with Pu intake; (ii) data on chelation therapy for a female; and (iii) fecal measurement results. Chelation therapy with DTPA is known to aid in reducing the internal radiation dose by enhancing the excretion of Pu from the body. Such enhancement affects Pu biokinetics in the human body, posing a challenge to the internal dose assessment. The current dose assessment practice is to exclude the data affected by DTPA from the analysis. Using this standard approach, i.e., only using data obtained 100 days after the last DTPA administration, the worksite’s Radiation Protection personnel estimated the ²³⁹Pu intake to be 73 Bq, with a committed effective dose equivalent to the whole-body of 16 mSv and a committed organ dose equivalent to the bone surfaces of 340 mSv. The present analysis is the first attempt to model explicitly the combined biokinetics of Pu and DTPA by using a newly developed chelation model. The bioassay data collected during and after the DTPA administrations were used for biokinetic modeling and dose assessment. The Markov Chain Monte Carlo method was used to investigate model parameter uncertainty, given the bioassay data and assumed prior probability distributions. Preliminary results of this study show that the worker’s Pu intake was 21 Bq, with a committed effective dose to the whole-body of 2.31 mSv and a committed equivalent dose to the bone surfaces of 66.7 mSv. Differences in results are expected not only because of the different dosimetric systems used, but also because this analysis includes chelation-affected bioassay data and uses a biokinetic model that accounts for the effect of chelation therapy in removing Pu from the body. [USTUR-0655-23A]

Ronald Goans (MJW Corporation), Lawrence Dauer (Memorial Sloan Kettering), Carol Iddins (ORISE REAC/TS), Michael Mumma (Vanderbilt University), Stacey McComish (USTUR), Sergey Tolmachev (USTUR)

The radium dial painters (RDP) are a well-described group of predominantly young women who incidentally ingested ²²⁶Ra and ²²⁸Ra as they painted luminescent watch dials in the first part of the twentieth century. In 1976 pathologist Dr. William D. Sharpe published complete clinical and autopsy results for 42 former radium dial painters evaluated in the New Jersey Radium Research Project (NJRRP). This was an important paper due to the completeness of the observations. Surprisingly, in the NJRRP study, clinicians noted a 35.5% incidence of hearing loss, both conductive and mixed etiologies. Since the 1976 publication, there has developed a considerable literature on radiation-induced hearing loss in patients undergoing radiotherapy for head and neck cancers. Recently, the neutrophil to lymphocyte ratio (NLR) has been shown in many cancer and non-cancer studies to be a nonspecific marker of inflammation. In prior collaborative efforts with the United States Transuranium and Uranium Registries and with the NCRP Million Person Study, it has been possible to evaluate NLR from medical records of a cohort of 166 former radium dial painters previously evaluated at Argonne National Laboratory. These observations have suggested a possible state of chronic inflammation in those patients previously treated for radium-induced osteosarcoma. Revisiting the hematology profiles in the NJ cohort, we find the group NLR to be statistically elevated (3.05 ± 0.28, n = 50; p = 0.002; Mann-Whitney) from that for modern unirradiated controls (2.06 ± 0.06, n = 125). These results are suggestive of chronic inflammation in the NJRRP cohort. The association of radiation-induced inflammation to hearing loss in the RDP cohort warrants additional investigation. [USTUR-0665-23A]

Xirui Liu (USTUR), Stacey McComish (USTUR), Sergey Tolmachev (USTUR), Joey Zhou (DOE)

Death certificates are commonly used as a primary source of information in epidemiological studies investigating the relationship between radiation exposure and health outcomes. However, it is known that death certificates may misclassify the underlying cause of death. At the United States Transuranium and Uranium Registries, these misclassification errors have been observed at an overall rate of 25.5% for a group of 275 individuals with internal deposition of actinide elements. This simulation study aims to evaluate whether there is a statistically significant impact on risk estimates resulting from misclassifications. For the analysis, the logistic regression model was used as the risk model. Dose datasets were generated using a log-normal distribution with predefined values for the geometric mean and the geometric standard deviation. Subsequently, outcomes were randomly generated using a predefined odd ratio and baseline prevalence. Varied rates of over- and under-classification were evaluated to assess the impact of misclassification on the risk estimate results. With a predefined odd ratio of 1 (e.g. no statistical association), misclassification errors on death certificates can result in statistically significant odds ratios from 10% to 35% of the time. Further simulation studies will explore the impact of misclassification of outcome on risk estimates by various factors such as different risk levels, baseline prevalence, different types of dose distributions, and sample sizes. [USTUR-0656-23A]

Presentation slides

Nicole Martinez (Clemson University/ORNL), Derek Jokisch (Francis Marion University/ORNL), Michael Mumma (Vanderbilt University), Sergey Tolmachev (USTUR), Maia Avtandilashvili (USTUR), George Tabatadze (USTUR), Richard Leggett, Caleigh Samuels (ORNL-CRPK), Lawrence Dauer (Memorial Sloan Kettering), John Boice (NCRP)

The radium dial workers (RDW) comprise a well-known and influential cohort of primarily young women occupationally exposed to radium through the painting of dials and gauges with radioluminescent paint. The last epidemiological follow-up of this cohort was over 30 years ago, as the Radium Studies program at Argonne National Laboratory (ANL) was terminated in the early 1990s. The study of the RDW is being revisited to include updated dosimetric analyses as part of the Million Person Study (MPS) of low-dose health effects in healthy American workers and veterans. An informative and fairly unique source of data and data contextualization is the availability of extensive (>500 GB) electronic (i.e., scanned) records from existing microfilm (roll or reel of film) and microfiche (flat sheets/cards). When the radium program at ANL was canceled, tissue samples were transferred to the United States Transuranium and Uranium Registries (USTUR) at Washington State University to be stored at the National Human Radiobiology Tissue Repository. Surprisingly there was a lingering debate on whether the written records and radiographs would be scanned/copied and preserved. Advocates for archiving persevered, and the foresight and dedication of that team has provided our current team incredible insight into the program and processes involved in the extensive prior work related to RDW. Although the type, extent, and quality (e.g., legibility) of record(s) varies between individuals, examples include in vivo radiation measurements (e.g., radon breath, whole body counts), autopsy results, medical records (including copies of radiographs), and various correspondence. Of particular dosimetric interest are 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 time series of measurements was chosen to assign an intake, or if there were concerns about a particular measurement. Taking care to preserve anonymity and dignity of the workers, we review herein typical information available in the aforementioned microfiche and microfilm, highlighting some historically interesting finds, and discuss the relevance to current and ongoing work related to revisiting the dosimetry of the RDW in the MPS. The availability of tissues from RDWs at the USTUR will supplement the archival written record. This has been one of the seminal and influential epidemiological studies ever conducted and the current follow-up with modern dosimetry will provide new information on the lifetime risks associated with ingestion of radium. [USTUR-0664-23A]

Deepesh Poudel (LANL), John Klumpp (LANL), Maia Avtandilashvili (USTUR), Sergey Tolmachev (USTUR)

The radiation dose imparted by plutonium (Pu) to the respiratory tract, and consequently the risk from inhalation of Pu, depends on the residence time, location, and the mechanism of retention. One of the mechanisms for long term retention of Pu is ‘binding,’ by which a fraction of the dissolved material chemically binds to the tissue of the airway wall. The International Commission on Radiological Protection proposes a bound fraction of 0.2% for Pu, inferred from the findings of animal and human studies. A critical evaluation of these studies, along with other evidence in the literature and additional datasets from the United States Transuranium and Uranium Registries, strongly suggest that a mechanism other than chemical binding is responsible for the long-term retention of Pu in the respiratory tract. Analyses of historical animal datasets (rats and non-human primates injected with Pu) and a dataset on post-mortem retention in the respiratory tract of a wound case indicate some systemic uptake by the respiratory tract. However, this systemic uptake alone does not fully explain the observed post-mortem retention in an individual who had inhaled highly soluble Pu nitrate. A review of the literature review indicates the presence of – and a significant retention of – Pu in the scar tissues of the respiratory tract. Accordingly, an alternate model with scar-tissue compartments is proposed to explain the retention of plutonium in the respiratory tract compartments of four workers. [USTUR-0668-23A]

Martin Šefl (USTUR), Maia Avtandilashvili^† (USTUR), Joey Zhou (DOE), Sergey Tolmachev (USTUR)

Monitoring bioassay data, such as urinary excretion and in-vivo chest counts, is the primary source of information for radiation epidemiological studies of nuclear workers. Bayesian analysis provides a distribution of dose estimates rather than a single value that is commonly used in radiation epidemiology. Using distributions allows for more sophisticated uncertainty estimates of organ activities and associated doses. The United States Transuranium and Uranium Registries (USTUR) stores monitoring data with post-mortem radiochemical analyses of tissues. Uncertainties in organ activities and radiation dose estimates from internally deposited ²³⁹Pu were evaluated using a group of 20 former nuclear workers. These individuals voluntarily donated their tissues to the USTUR. Ten workers were exposed to soluble Pu-nitrate and ten workers to ‘high-fired’ PuO₂ aerosols. Plutonium bioassay data for everyone included at least five positive urine measurements. The measured ²³⁹Pu activities ranged from 9.6 to 920 Bq in the liver, from 9.2 to 774 Bq in the skeleton, and from 7.2 to 6,550 Bq in the lungs. Latin hypercube sampling was employed to create priors of main absorption parameters (rapidly dissolved fraction and slow dissolution rate) and selected particle transport rates. Distributions of ²³⁹Pu organ doses were generated. The distributions of doses based on ²³⁹Pu bioassay measurements were compared to the point estimates based on the measured post-mortem ²³⁹Pu activities in the lungs and liver+skeleton. Furthermore, the extent of distribution coverage of the post-mortem point estimate was evaluated. ^†Presenter. [USTUR-0657-23A]

Poster

Daniel J. Strom (USTUR), George Tabatadze (USTUR)

The United States Transuranium & Uranium Registries (USTUR) is a U.S. Department of Energy funded research program at the Washington State University that studies deposition, biokinetics, dosimetry, and possible biological effects of actinides such as plutonium, americium, and uranium. Other radionuclides of interest for analysis at the USTUR include thorium, radium, curium, and neptunium. USTUR registrants are former nuclear workers with measurable, documented exposures to TRU elements who voluntarily donated their organs and tissues to science for post-mortem study.

Systemic plutonium and americium concentrate in the liver and skeleton, while uranium primarily concentrates in the skeleton. Inhalation and wound intakes are most common routes of intake. Lungs, thoracic lymph nodes, liver, skeleton, and, for a wound intake, wound site and axillary lymph nodes are collected and analyzed. For “whole body donors,” many more tissues and organs are included.

Our measurands (the quantities intended to be measured) are activity and activity concentration in tissues and organs. To illustrate how we estimate these measurands from measurement results, we present the entire radiochemistry program, from sample collection at autopsy to the inference of activity and activity concentration in tissues and organs. Sample preparation by dry ashing, microwave digestion, chemical separation of elements, addition of tracers for estimation of radiochemical recovery, and electrodeposition are shown.

The program is presented in a MARLAP framework of measurement quality objectives (MQOs) and data quality objectives (DQOs) with a focus on uncertainty propagation and data management. To demonstrate compliance with MQOs, we calculate the predicted “activity-on-a-planchet” that would be expected 50 years after an intake of 74 Bq (2 nCi) for lung, liver, and skeleton to demonstrate that our radiochemical methods provide data of usable quality. Uncertainties in activity are calculated as a function of background counts and various other uncertain parameters. Methods used in calculations of counting efficiencies and radiochemical recovery are presented. Data and measurement system performance indicators, such as critical value (SC), p-value, minimum detectable activity (MDA), and minimum quantifiable activity (MQA), are calculated and recorded. Calculations are done with the “N+1” option presented in MARLAP. The overall Quality Assurance program is cast in numerical terms with control levels and tolerance limits. [USTUR-0683-24P]

Daniel Strom (USTUR)

For decades, the mantra of “time, distance, and shielding” has dominated worker training in radiation protection. While memorable, these 3 concepts are woefully incomplete and do not describe actions. To provide a much more complete menu of options that include actions outside of the ICRP’s system of protection, the author published 10 principles and 10 commandments of radiation protection in 1996 (Health Phys 70(3): 388-393). The principles describe the variables that can be controlled (whether by an individual or an organization), followed by actions (“commandments”) that can be taken for each variable, separated into external exposure situations and intake-of-radioactive-material situations. The commandments are expressed in both familiar terms and in technical terms. The principles are 1) time, 2) distance/direction, 3) dispersal, 4) source reduction, 5) source barrier (engineered controls), 6) personal barrier (PPE), 7) decorporation, 8) effect mitigation, 9) optimal technology, and 10) limitation of other exposures. The simple-language commandments are 1) hurry (but don’t be hasty); 2) stay away from it or stay upwind of it; 3) disperse and dilute it; 4) make and use as little as possible; 5) keep it in; 6) keep it out; 7) get it out of you and off of you; 8) limit the damage; 9) choose the best technology; and 10) don’t compound risks (don’t smoke). Only a few items have been added in 28 years. Direction (stay upwind) has been added to the distance principle/ commandment. One commandment has been added to the personal barrier principle, “hold your breath.” While no one should ask a worker to do this, but it could save an individual’s life or dramatically reduce their intake under some emergency circumstances. Under the principle of source reduction, the prevention of attacks on nuclear power plants should be included with the prevention of the use of nuclear weapons. [USTUR-0681-24]

George Tabatadze (USTUR), Daniel Strom (USTUR), Maia Avtandilashvili (USTUR), Stacey McComish (USTUR), Sergey Tolmachev (USTUR)

The United States Transuranium and Uranium Registries (USTUR) is a U.S. Department of Energy funded research program at the Washington State University that studies deposition, biokinetics, and dosimetry of actinides such as plutonium, americium, and uranium. Other radionuclides of interest for analysis at the USTUR include ²²⁶Ra, ²³²Th, ²³⁷Np, and ²⁴⁴Cm. The USTUR radiochemical laboratory analyzes human tissues from deceased former nuclear workers who have donated selected organs/ tissues or entire bodies to the Registries. Plutonium and americium are radiochemically separated from digested tissues, electrodeposited onto a planchet, and measured by alpha spectrometry. Each sample is counted for 150,000 s with an associated background measurement of 300,000 s. This presentation is part of the development of Measurement Quality Objectives (MQOs) for the USTUR’s Radiochemistry Program. It specifically addresses the minimum detectable activity (MDA) and the development of a measurement sensitivity MQO associated with the anticipated activity of a sample (i.e., expected activity on a planchet). Using this concept, the Registries characterizes its alpha spectrometry counting system based on an assumed actinide uptake of 74 Bq, 50 years prior to measurement, considering factors associated with the exposure scenario such as the chemical and physical form of the radioactive material, primary radionuclide, and route of intake. The resulting summary table highlights areas of technological limitations, prompting a subsequent discussion on potential measurement alternatives. Current radiochemical analysis procedures are more than adequate to detect activities of ²³⁹Pu and ²⁴¹Am in the lungs, liver, and skeleton for most of the Registrants. [USTUR-0658-23A]

Poster

Sergey Tolmachev (USTUR), Florencio Martinez (USTUR), Jessica Linson (University of Missouri), John Brockman (University of Missouri), Elizabeth Thomas (USTUR), Maia Avtandilashvili (USTUR), George Tabatadze (USTUR), Richard Leggett (ORNL), Caleigh Samuels (ORNL-CRPK), Nicole Martinez (Clemson University), Derek Jokisch (Francis Marion University), John Boice (NCRP), Lawrence Dauer (Memorial Sloan Kettering)

Since 1968, the U.S. Transuranium and Uranium Registries (USTUR) has studied the biokinetics and tissue dosimetry of uranium and transuranium elements in nuclear workers. For 50 years, the mission of the USTUR has been “to refine dose assessment methods in support of reliable epidemiological studies, radiation risk assessment, and regulatory standards for radiological protection of workers and general public.” The Registries works closely with ICRP, NCRP, and Oak Ridge National Laboratory. In 1992, the National Human Radiobiology Tissue Repository (NHRTR) was established at the USTUR. The NHRTR holds biological specimens from USTUR tissue donors, as well as samples from U.S. Radium Studies acquired from Argonne National Laboratory in 1993. As part of the USTUR collaboration with the Million Person Study (MPS), radiation dose to different parts of the human heart was estimated for workers with documented intakes of ²³⁹Pu or ²²⁶Ra. The distribution of radionuclides, expressed in terms of concentration (Bq per kg of tissue) serves as a surrogate for radiation dose. Based on available organs from workers who donated their bodies or tissues for research, nine undissected hearts were identified: seven from USTUR Registrants with plutonium exposure (males) and two from radium workers (female and male). For the plutonium workers, estimated ²³⁹Pu systemic deposition ranged from < 7 4 Bq to 2,272 Bq. For the radium workers, estimated ²²⁶Ra systemic deposition was 10.1 MBq for the female dial painter and 14.8 kBq for the male worker. Organ dissection was based on a heart model published by Borrego et al (2019). This model includes nine cardiac substructures: aorta, left main coronary artery, left atrium, left anterior descending artery, left circumflex artery, left ventricle, right atrium, right coronary artery, and right ventricle. A total of 102 cardiac tissue samples was collected from nine cases – 78 from the seven USTUR cases and 24 from the two radium cases. Besides 81 samples from nine cardiac substructures, the following tissues were also collected: mitral (left) valve (7), tricuspid (right) valve (7), epicardial fat (6), and coronary bypass (1). In addition to tissues, blood (cardiac fluids) samples were collected for all nine workers resulting in 111 samples for radiochemical analyses. After tissue acid digestion, samples were analyzed for ²³⁹Pu, ²⁴⁰Pu, and ²²⁶Ra isotopes by inductively coupled plasma mass spectrometry. These results are intended to support worker health studies by improving associated dosimetric and epidemiological models. The MPS has evaluated mortality from ischemic heart disease (IHD) for over 500,000 workers. Workers with intakes of plutonium and radium are unique in having heart tissue exposed to high-LET radiation, i.e., alpha particles. These dosimetric analyses will be generalized and incorporated into the dose-response analyses for IHD for workers at Los Alamos, Rocky Flats, Mallinckrodt and other facilities. These data are of special value to long-term space exploration where galactic cosmic rays will expose all tissues, including the heart, to high-LET radiation for long periods of time. These dose evaluations are relevant to the expanding field of theranostics that applies alpha-particle emitters in the diagnosis and treatment of tumors. [USTUR-0663-23A]