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U.S. Transuranium and Uranium Registries Conference Contributions

Health Physics Society Meeting, Raleigh, NC, July 9-13, 2017

USTUR faculty members were authors on three presentations at the 62nd Annual Health Physics Society Meeting in July 2017. Additionally, USTUR/COP research student, Sara Dumit, presented her dissertation work.

U.S. Transuranium and Uranium Registries: 50 y of research relevant to new biomarker

Sergei Y. Tolmachev (USTUR)

The potential toxicity of plutonium and other artificially-produced actinide elements was recognized during the early days of the Manhattan Project. The mission of the United States Transuranium and Uranium Registries (USTUR) is to study the uptake, translocation, retention and excretion (biokinetics), and tissue dosimetry of uranium, plutonium, americium, and other actinides in occupationally exposed volunteer Registrants (tissue donors). The USTUR is an invaluable national and international resource for testing and improving the application of bioassay data to predict tissue dose rates measured at autopsy. These studies are fundamental to evaluating and improving the reliability of, and confidence in, both prospective and retrospective assessments of tissue doses and risks from intakes of actinides. Washington State University has successfully operated the USTUR and the associated National Human Radiobiology Tissue Repository (NHRTR) since 1992, as a grant research project administered by the College of Pharmacy. Currently, the USTUR holds records and data for 304 partial-body donors and 43 whole-body donors. The NHRTR has preserved and held frozen tissue samples, histological slides, and formalin-fixed paraffin-embedded tissue blocks from 151 donations (109 partial-body and 32 whole-body). NHRTR materials are, however, valuable unexplored resource for the biomarker and cytogenetic studies. Recently conducted study by Radiation Emergency Assistance Center and Training Site (REAC/TS) in collaboration with the USTUR demonstrated that the Pseudo Pelger-Hüet anomaly could be used as a permanent radiation biomarker. [USTUR-0475-17A]

Presentation Slides

Plutonium in tissues of occupationally exposed individuals

George Tabatadze (USTUR), Maia Avtandilashvili (USTUR), Sergei Tolmachev (USTUR)

The United States Transuranium and Uranium Registries (USTUR) studies actinide biokinetics and tissue dosimetry by following up occupationally exposed workers. The USTUR research relies heavily upon postmortem autopsy findings and radiochemical analysis of tissues. Tissue analysis provides data on actinide distribution, retention, and radiation dose estimation from internally deposited radionuclides. In this study, 1,678 tissue samples from 295 voluntary donors to the USTUR were analyzed for plutonium using alpha-spectroscopy. The activity concentrations of 239+240Pu were measured in 288 lung tissues, 265 thoracic lymph nodes (LNTH), 285 liver samples, and 840 bones from 253 cases. For each case, average 239+240Pu concentration in skeleton was calculated. The 239+240Pu activity concentrations in lungs ranged from 0.55 mBq kg-1 to 7.23 kBq kg-1 (median: 1.29 Bq kg-1); in LNTH from 1.79 mBq kg-1 to 68.4 kBq kg-1 (median: 18.8 Bq kg-1); in liver from 0.45 mBq kg-1 to 0.92 kBq kg-1 (median: 1.23 Bq kg-1), and in skeleton from 3.55 mBq kg-1 to 0.21 kBq kg-1 (median: 0.35 Bq kg-1). The LNTH-to-lung activity concentration ratios were calculated for 258 cases. The ratios ranged from 0.01 to 561, with median of 17. This indicates that majority of the USTUR donors were exposed to insoluble plutonium material. Total activities in liver and skeleton were estimated using ICRP Reference Man organ weights. Liver-to-skeleton activity ratios were calculated for 238 cases with median of 0.71, resulting in 1:1.4 plutonium systemic distribution between liver and skeleton. This is inconsistent with the ICRP assumption that plutonium is equally distributed between liver and skeleton. [USTUR-0476-17A]

Presentation Slides

Enhancement of plutonium excretion following lte Ca-EDTA/DTPA treatment

Sara Dumit (USTUR/COP), Maia Avtandilashvili (USTUR), Sergei Tolmachev (USTUR)

Individuals with significant internal deposition of plutonium are likely to be treated with intravenous injections of chelating agents such as the calcium or zinc salts of ethylene diamine tetraacetic acid (EDTA) and diethylene triamine pentaacetic acid (DTPA). Chelation with Ca-DTPA is known to enhance urine excretion of plutonium by up to a factor of 100. The enhancement factor (EF) may be higher for soluble plutonium compounds and varies significantly among individuals. Knowing the EF is critical for interpretation of bioassay data collected during the chelation therapy. The EF is an important parameter for estimation of radionuclide intake and radiation dose assessment using standard biokinetic models. In current practice, and in the absence of individual-specific data, a value of 50 is recommended. In this single-case study, plutonium EFs were estimated for late treatments with EDTA (9 mo after intake) and DTPA (7.2 y after intake). These treatments consisted of 4 g of Ca-EDTA daily for 5 d, and of 1 g of Ca-DTPA weekly for 11 wk. In the case of EDTA treatment, the Pu EFEDTA ranged from 71 to 159, with a geometric mean of 101. For DTPA, the Pu EFDTPA ranged from 8 to 192, with a geometric mean of 33. Enhancement factors estimated in this work are in the range of published values. The finding that EFDTPA is lower than the EFEDTA is likely due to decreasing over time of systemic plutonium available for complexation. [USTUR-0477-17A]

Presentation Slides

The pseudo Pelger-Hüet cell – From bats to humans and everything in between

Ronald Goans (MJW Corp.), Carol Iddins (REAC/TS), Richard Toohey (MJW Corporation), Stacey McComish (USTUR), Sergei Tolmachev (USTUR), Nicholas Daniak (REAC/TS)

The Pelger-Hüet anomaly (PHA) has been recently described as a novel, semi-permanent, radiation-induced biomarker in circulating neutrophils, and it appears to be a surrogate for radiation dose to bone marrow. The PH cell, described by Pelger (1928) and Hüet (1931), is a bi-lobed neutrophil characterized by a thin chromatin bridge. In humans, PHA derives from an autosomal dominant mutation on the long arm of chromosome 1, 1q42.12. PHA is seen by physicians treating patients with leukemia and also as a reaction to certain drugs. Our work is the first to show that the anomaly is observed in human radiation exposure. PHA is also seen in animals (dogs, cats, horses, bats) and a recent Ph.D. thesis examined PHA in bats living in low and high radiation background areas in a monazite cave. In this presentation, we will summarize animal research, our analysis of the 1958 Y-12 cohort, the 1971 CARL 60Co accident, and a collaborative effort with the U.S. Transuranium and Uranium Registry (USTUR). In the USTUR study, we have examined PHA in peripheral blood slides from a cohort of 166 former radium dial painters. Members of this radium dial painter cohort had ingestion of 226Ra and 228Ra at an early age (average age 20.6 ± 5.4 y; range 13-40 y) during the years 1915-1950. In the context of these experiments, Receiver Operating Curve (ROC) methodology can be used to evaluate the PHA% as a binary laboratory test to determine whether there is dose to bone marrow. A cut-point of 5.74% PHA is found for identification of the dose category (AUC 0.961, sensitivity 97.8%, specificity 74.2%, PPV 94.3% for the USTUR dataset). PHA from peripheral blood is therefore a reasonable dose surrogate for dose to bone marrow. Acknowledgements: this work was supported by the U.S. Department of Energy under contract number DE-AC05- 06OR23100 with Oak Ridge Associated Universities and award number DEHS0000073 to Washington State University. [USTUR-0482-17A]