Chelation Modeling of a Plutonium-238 Inhalation Incident Treated with Delayed DTPA.

This work describes an analysis, using a previously established chelation model, of the bioassay data collected from a worker who received delayed chelation therapy following a plutonium-238 inhalation. The details of the case have already been described in two publications. The individual was treated with Ca-DTPA via multiple intravenous injections and then nebulizations beginning several months after the intake and continuing for four years. The exact date and circumstances of the intake are unknown. However, interviews with the worker suggested that the intake occurred via inhalation of a soluble plutonium compound. The worker provided daily urine and fecal bioassay samples throughout the chelation treatment protocol, including samples collected before, during, and after the administration of Ca-DTPA. Unlike the previous two publications presenting this case, the current analysis explicitly models the combined biokinetics of the plutonium-DTPA chelate. Using the previously established chelation model, it was possible to fit the data through optimizing only the intake (day and magnitude), solubility, and absorbed fraction of nebulized Ca-DTPA. This work supports the hypothesis that the efficacy of the delayed chelation treatment observed in this case results mainly from chelation of cell-internalized plutonium by Ca-DTPA (intracellular chelation). It also demonstrates the validity of the previously established chelation model. As the bioassay data were modified to ensure data anonymization, the calculation of the "true" committed effective dose was not possible. However, the treatment-induced dose inhibition (in percentage) was calculated.

Biokinetic model analysis with DTPA administration for a case of accidental inhalation of actinides in Japan.

Accidental inhalation intake of plutonium isotopes and 241Am occurred at a Pu research facility in Japan in 2017, and the five workers involved in this accident were treated by the administration of Ca/Zn-diethylenetriaminepentaacetic acid (DTPA). For the worker who was most internally exposed, the therapy was continued over 1 y after the accident. Urinary samples collected before and after each administration were subject to bioassay to evaluate the efficacy of the dose reduction. This study performed numerical analyses using a biokinetic model dealing with 241Am-DTPA with reference to the European Coordinated Network on Radiation Dosimetry approach, which assumes that the complex of actinides and Ca/Zn-DTPA is generated in the designated compartments in the biokinetic model. The results of the model prediction well captured the trend of the observed urinary excretion in the long-term bioassay and would be useful to evaluate the efficacy of the Ca/Zn-DTPA administration for the worker involved in the accident.

Dose reconstruction for plutonium-239 intakes at the Rocky Flats Plant.

PURPOSE: The Rocky Flats (RF) Plant was a weapons manufacturing facility that operated from the early 1950s to 1989. Its primary missions were the production of plutonium (Pu) pits for thermonuclear weapons and the processing of retired weapons for Pu recovery. The purpose of this study was to estimate radiation doses to a cohort of 4499 RF workers from an intake of 239Pu, the primary plutonium isotope handled at the site. MATERIALS AND METHODS: The latest biokinetic models of the International Commission on Radiological Protection, or site-specific variations of those models, were used to estimate 239Pu intakes for each worker based on model fits to bioassay data often coupled with lung measurements. RESULTS: Urinary excretion and lung retention data for most 239Pu intakes could be fit reasonably well by a mixture of Pu dioxide and moderately soluble material. For some workers, better fits were obtained by application of other absorption types including Type S, 239Pu nitrate, or pure 239Pu dioxide, or by assuming intake via a wound. The lungs typically received the highest tissue doses, with fifty-year committed equivalent doses in the range of 0.5-1 Sv for 275 workers, 1-5 Sv for 115 workers, and greater than 5 Sv for 12 workers. CONCLUSIONS: RF was a unique site regarding a large number of lung measurements available for determining the appropriate absorption types for inhaled material. This provided higher confidence in reconstructed 239Pu doses than is generally gained from urinary data alone.

Dose Assessment Following a 238 Pu Inhalation Incident at Los Alamos National Laboratory.

ABSTRACT: A glovebox breach at the plutonium facility at Los Alamos National Laboratory potentially exposed 15 individuals to 238 Pu aerosols. One of the individuals (P0) received two 1-g intravenous DTPA treatments, one on the day of the intake and another the following day. Several urine samples were collected from the individuals involved in the incident. Particle size analysis on the PPE and solubility analysis of the particles on a filter sample were conducted in vitro. The applicability of the results from the in vitro studies for dose assessment was questionable because of the effect of the cloth mask the workers were wearing for COVID-related protection. Based on several considerations, including the effect of cloth masks on the "effective" particle size inhaled and the analysis of fecal-to-urine ratio, the default Type M 1 µm AMAD model was used to estimate intakes and doses. Using the urinary excretion data collected after 100 d post last chelation treatment, the committed effective dose, E(50), for P0 was calculated to be 5.2 mSv. For all others, the bioassay data were consistent with no intakes or very small intakes [corresponding to E(50) less than 0.1 mSv].

Plutonium in Manhattan Project workers: Using autopsy data to evaluate organ content and dose estimates based on urine bioassay with implications for radiation epidemiology.

PURPOSE: Radiation dose estimates in epidemiology typically rely on intake predictions based on urine bioassay measurements. The purpose of this article is to compare the conventional dosimetric estimates for radiation epidemiology with the estimates based on additional post-mortem tissue radiochemical analysis results. METHODS: The comparison was performed on a unique group of 11 former Manhattan Project nuclear workers, who worked with plutonium in the 1940s, and voluntarily donated their bodies to the United States Transuranium and Uranium Registries. RESULTS: Post-mortem organ activities were predicted using different sets of urine data and compared to measured activities. Use of urinalysis data collected during the exposure periods overestimated the systemic (liver+skeleton) deposition of 239Pu by 155±134%, while the average bias from using post-exposure urinalyses was -4±50%. Committed effective doses estimated using early urine data differed from the best estimate by, on average, 196±193%; inclusion of follow-up urine measurements in analyses decreased the mean bias to 0.6±36.3%. Cumulative absorbed doses for the liver, red marrow, bone surface, and brain were calculated for the actual commitment period. CONCLUSION: On average, post-exposure urine bioassay results were in good agreement with post-mortem tissue analyses and were more reliable than results of urine bioassays collected during the exposure.

Maximum Possible Doses for a Cohort of Individuals with Intakes Possibly Containing a Component of a Ceramic-type Material.

ABSTRACT: Recently, a glovebox breach led to the potential exposure of 15 Los Alamos National Laboratory employees to 238Pu. Given what is known about the material involved in the incident, the possibility of an intake with a ceramic-type component must be considered. Incidents in which intakes of ceramic solubility-type material is suspected represent a challenge for internal dose assessment via urine bioassay because even relatively large doses cannot be detected in urine until many months after the intake. Ideally, in these situations fecal samples should be collected to assess the intake, but in this case fecal sampling was delayed. This paper presents a method to calculate the maximum possible doses for all individuals involved in an incident using only early time-decreasing urine bioassay measurements.

Dose Assessment Following a 238Pu-contaminated Wound Case with Chelation and Excision.

The urinary excretion and wound retention data collected after a Pu-contaminated wound were analyzed using Markov Chain Monte Carlo (MCMC) to obtain the posterior distribution of the intakes and doses. An empirical approach was used to model the effects of medical treatments (chelation and excision) on the reduction of doses. It was calculated that DTPA enhanced the urinary excretion, on average, by a factor of 17. The empirical analysis also allowed calculation of the efficacies of the medical treatments-excision and chelation averted approximately 76% and 5.5%, respectively, of the doses that would have been if there were no medical treatment. All bioassay data are provided in the appendix for independent analysis and to facilitate the compartmental modeling approaches being developed by the health physics community.

Response to a Skin Puncture Contaminated with 238Pu at Los Alamos National Laboratory.

The three principal pathways for intakes of plutonium are ingestion, inhalation, and contaminated wounds. In August 2018, a glovebox worker at Los Alamos National Laboratory (LANL) sustained a puncture from a thread of a braided steel cable contaminated with Pu. The puncture produced no pain, no blood, and little or no visible mark. As a result, the potential for a contaminated wound was not immediately recognized, and a wound count was not conducted until elevated urine bioassay results were received 12 d after the incident. This paper discusses the circumstances of the incident, along with the medical response and dose assessment, and a discussion of the risks and benefits of the medical interventions.

The effects of chronic diseases on plutonium urinary excretion in former workers of the Mayak Production Association.

The radiochemical analysis of plutonium activity in urine is the main method for indirect estimation of doses of internal exposure from plutonium incorporation in professional workers. It was previously shown that late-in-life acute diseases, particularly those that affect the liver, can promote accelerated rates of release of plutonium from the liver with enhanced excretion rates. This initial study examines the relationships of some chronic diseases on plutonium excretion as well as the terminal relative distribution of plutonium between the liver and skeleton. Fourteen cases from former workers at the Mayak Production Association (Mayak PA) who provided from 4-9 urine plutonium bioassays for plutonium, had an autopsy conducted after death, and had sufficient clinical records to document their health status were used in this study. Enhanced plutonium excretion was associated with more serious chronic diseases, including cardiovascular diseases and other diseases that involved the liver. These chronic diseases were also associated with relatively less plutonium found in the liver relative to the skeleton determined by analyses conducted after autopsy. These data further document health conditions that affect plutonium biokinetics and organ deposition and retention patterns and suggest that health status should be considered when conducting plutonium bioassays as these may alter subsequent dosimetry and risk models.

Building a job-exposure matrix for early plutonium workers at the Sellafield nuclear site, United Kingdom.

The potential for adverse health effects from internal exposure to Plutonium has been recognised since its discovery in the 1940s. However, in the absence of specific information, potential risks from Plutonium exposure have always largely been controlled through knowledge of radiation exposure risks in general, much of which comes from external radiation exposures. To try to obtain more direct estimates of potential internal exposure risks, epidemiological studies of Plutonium workers need to be conducted. Such epidemiological analyses require individual Plutonium exposure estimates that are as accurate and unbiased as possible. The UK Sellafield workforce includes one of the world's largest cohorts of Plutonium workers, which constitutes, by some considerable margin, the group of workers most comprehensively monitored for internal exposure to this alpha-particle-emitter. However, for several hundred workers employed at the start of Plutonium work at the facility, during the period from 1952 through to 1963, the historical urinalysis results available cannot provide sufficiently accurate and unbiased exposure assessments needed for use in epidemiological studies. Consequently, these early workers have had to be excluded from epidemiological analyses and this has significantly reduced the power of these studies. A promising quantitative methodology to overcome the issue of missing or deficient exposure data, is to use exposure data from other sources to estimate the average exposure a 'typical worker' would have received, and to collate this information for specific occupations and years. This approach is called a Job-Exposure Matrix (JEM). Work on a pilot study to construct a population-specific quantitative JEM for the early Plutonium workers at Sellafield during 1952-1963, for whom reliable urinalysis results do not exist, has shown the potential for a JEM approach to produce more reliable and useful exposure estimates for epidemiological research.

Validation of a system of models for plutonium decorporation therapy.

A recently proposed system of models for plutonium decorporation (SPD) was developed using data from an individual occupationally exposed to plutonium via a wound [from United States Transuranium and Uranium Registries (USTUR) Case 0212]. The present study evaluated the SPD using chelation treatment data, urine measurements, and post-mortem plutonium activities in the skeleton and liver from USTUR Case 0269. This individual was occupationally exposed to moderately soluble plutonium via inhalation and extensively treated with chelating agents. The SPD was linked to the International Commission on Radiological Protection (ICRP) Publication 66 Human Respiratory Tract Model (HRTM) and the ICRP Publication 30 Gastrointestinal Tract model to evaluate the goodness-of-fit to the urinary excretion data and the predictions of post-mortem plutonium retention in the skeleton and liver. The goodness-of-fit was also evaluated when the SPD was linked to the ICRP Publication 130 HRTM and the ICRP Publication 100 Human Alimentary Tract Model. The present study showed that the proposed SPD was useful for fitting the entire, chelation-affected and non-affected, urine bioassay data, and for predicting the post-mortem plutonium retention in the skeleton and liver at time of death, 38.5 years after the accident. The results of this work are consistent with the conclusion that Ca-EDTA is less effective than Ca-DTPA for enhancing urinary excretion of plutonium.

Construction, Validation and Sensitivity Analyses of a Job Exposure Matrix for Early Plutonium Workers at the Sellafield Nuclear Site, United Kingdom.

Plutonium is a radiologically significant alpha-particle emitter. The potential for adverse health effects from internal exposures due to plutonium intakes has been recognized since the 1940s. The workforce of the Sellafield nuclear facility (Cumbria, UK), includes one of the world's most important groups of plutonium-exposed workers for studying the potential health risks of this internal exposure. However, for several hundred workers employed at the start of plutonium work at the facility (1952-1963), historical monitoring records based on measurements of urinary excretion of plutonium are not sufficiently reliable to provide the accurate and unbiased exposure assessments needed for epidemiological studies. Consequently, these early workers have had to be excluded from such studies, significantly reducing their power. We constructed a population-specific quantitative job exposure matrix (JEM) to estimate the average intakes of "typical plutonium workers" in this period, from 1952-1963, and assessed its validity and sensitivity to exposure assessment decisions. We conducted internal cross-validation using an a priori 10% extracted sample to evaluate reliability of estimates, explored JEM sensitivity to assumptions in the exposure assessment, and assessed the impact of uncertainty in urinalysis measurements on the precision of annual intake estimates using Markov Chain Monte Carlo (MCMC) methodology. Pairwise correlations ( RP) of estimated (JEM) and measured (10% sample) annual intakes were moderate to high ( RP > 0.4) for 10 out of 13 JEM groups, while absolute differences were <20% for 11 out of 13 JEM groups. There was little evidence of a temporal trend in correlations ( P = 0.13) or absolute differences ( P = 0.34). The median JEM-derived cumulative intake of 95.2 (IQR, 55.0-130.0) Bq was comparable to those based on alternative assumptions in the exposure assessment (median range, 95.2-100.0 Bq; 75th percentiles, 130.0-146.0 Bq). Measurement error simulation resulted in a 40-60% reduced median cumulative intake but higher maximum cumulative intakes. The JEM finds a balance between reliability and precision that makes it useful for epidemiological purposes and is relatively insensitive to specific choices in the exposure assessment. This JEM will allow the inclusion of workers with longest follow-up and who could not be included up until now in epidemiological studies without introducing significant bias.

Improved Modeling of Plutonium-DTPA Decorporation.

Individuals with significant intakes of plutonium (Pu) are typically treated with chelating agents, such as the trisodium salt form of calcium diethylenetriaminepentaacetate (CaNa3-DTPA, referred to hereafter as Ca-DTPA). Currently, there is no recommended approach for simultaneously modeling plutonium biokinetics during and after chelation therapy. In this study, an improved modeling system for plutonium decorporation was developed. The system comprises three individual model structures describing, separately, the distinct biokinetic behaviors of systemic plutonium, intravenously injected Ca-DTPA and in vivo-formed Pu-DTPA chelate. The system was linked to ICRP Publication 100, "Human Alimentary Tract Model for Radiological Protection" and NCRP Report 156, Development of a Biokinetic Model for Radionuclide-Contaminated Wounds and Procedures for Their Assessment, Dosimetry and Treatment." Urine bioassay and chelation treatment data from an occupationally-exposed individual were used for model development. Chelation was assumed to occur in the blood, soft tissues, liver and skeleton. The coordinated network for radiation dosimetry approach to decorporation modeling was applied using a chelation constant describing the secondorder, time-dependent kinetics of the in vivo chelation reaction. When using the proposed system of models for plutonium decorporation, a significant improvement of the goodness-of-fit to the urinary excretion data was observed and more accurate predictions of postmortem plutonium retention in the skeleton, liver and wound site were achieved.

Rapid determination of ultra-trace plutonium isotopes (239Pu, 240Pu and 241Pu) in small-volume human urine bioassay using sector-field inductively coupled plasma mass spectrometry.

A rapid method with enhanced 238U decontamination was developed for ultra-trace Pu analysis in small-volume urine bioassays. This method consists of acid digestion, co-precipitation, extraction chromatography and sector-field inductively coupled plasma mass spectrometry (SF-ICP-MS) measurement. Parameters that may influence the analytical performance were studied systematically. This method achieved a high 238U decontamination factor (3.8 × 106) and the 242Pu recovery was stable for 20 mL and 100 mL urine bioassays with an average value of 72.7 ±â€¯5.5%. The limits of detection for 239Pu, 240Pu and 241Pu by the method were 0.016 fg mL-1, 0.016 fg mL-1 and 0.019 fg mL-1 for 20 mL urine samples and 0.003 fg mL-1, 0.002 fg mL-1 and 0.003 fg mL-1 for 100 mL urine samples, respectively. Considering the small volume of urine employed in this study, the absolute detection limits of the method were comparable or even better than those measured with thermal ionization mass spectrometry and accelerator mass spectrometry. All procedures for 20 mL and 100 mL urine bioassays were completed in 9.5 h and 11 h, respectively, and analysis of 10 samples could be finished within one day. With the considerably low detection limits of Pu isotopes and high sample throughput, this method would be a promising tool for the quick response to radiological emergencies and for rapid screening of unexpected occupational exposures of workers involved in the future FDNPP reactor decommissioning operations.

On the sequential separation and quantification of 237Np, 241Am, thorium, plutonium, and uranium isotopes in environmental and urine samples.

The implementation of the one-pass-through separation technique using two stacked chromatography columns of TEVA - TRU resins for the separation of 237Np, 241Am, thorium, plutonium and uranium from environmental and urine samples was investigated. The sequential separation technique proved to be successful and gave similar results to those obtained when using individual separations. The analysis time was considerably improved. The amount of chemical waste was also reduced by 50% and the use of HClO4 was avoided. The technique of ICP-MS was also investigated as a complementary technique to alpha-spectrometry.

ANALYSIS OF URINARY EXCRETION DATA FROM THREE PLUTONIUM-CONTAMINATED WOUNDS AT LOS ALAMOS NATIONAL LABORATORY.

The National Council on Radiation Protection (NCRP)-156 Report proposes seven different biokinetic models for wound cases depending on the physicochemistry of the contaminant. Because the models were heavily based on experimental animal data, the authors of the report encouraged application and validation of the models using bioassay data from actual human exposures. Each of the wound models was applied to three plutonium-contaminated wounds, and the models resulted in a good agreement to only one of the cases. We then applied a simpler biokinetic model structure to the bioassay data and showed that fitting the transfer rates from this model structure yielded better agreement with the data than does the best-fitting NCRP-156 model. Because the biokinetics of radioactive material in each wound is different, it is impractical to propose a discrete set of model parameters to describe the biokinetics of radionuclides in all wounds, and thus each wound should be treated empirically.

Lung Cancer Risk from Plutonium: A Pooled Analysis of the Mayak and Sellafield Worker Cohorts.

In this study, lung cancer risk from occupational plutonium exposure was analyzed in a pooled cohort of Mayak and Sellafield workers, two of the most informative cohorts in the world with detailed plutonium urine monitoring programs. The pooled cohort comprised 45,817 workers: 23,443 Sellafield workers first employed during 1947-2002 with follow-up until the end of 2005 and 22,374 Mayak workers first employed during 1948-1982 with follow-up until the end of 2008. In the pooled cohort 1,195 lung cancer deaths were observed (789 Mayak, 406 Sellafield) but only 893 lung cancer incidences (509 Mayak, 384 Sellafield, due to truncated follow-up in the incidence analysis). Analyses were performed using Poisson regression models, and were based on doses derived from individual radiation monitoring data using an updated dose assessment methodology developed in the study. There was clear evidence of a linear association between cumulative internal plutonium lung dose and risk of both lung cancer mortality and incidence in the pooled cohort. The pooled point estimates of the excess relative risk (ERR) from plutonium exposure for both lung cancer mortality and incidence were within the range of 5-8 per Gy for males at age 60. The ERR estimates in relationship to external gamma radiation were also significantly raised and in the range 0.2-0.4 per Gy of cumulative gamma dose to the lung. The point estimates of risk, for both external and plutonium exposure, were comparable between the cohorts, which suggests that the pooling of these data was valid. The results support point estimates of relative biological effectiveness (RBE) in the range of 10-25, which is in broad agreement with the value of 20 currently adopted in radiological protection as the radiation weighting factor for alpha particles, however, the uncertainty on this value (RBE = 21; 95% CI: 9-178) is large. The results provide direct evidence that the plutonium risks in each cohort are of the same order of magnitude but the uncertainty on the Sellafield cohort plutonium risk estimates is large, with observed risks consistent with no plutonium risk, and risks five times larger than those observed in the Mayak cohort.

Plutonium Bioassay Testing of United States Atmospheric Nuclear Test Participants and Occupation Forces of Hiroshima and Nagasaki, Japan.

The pilot urine plutonium bioassay testing program engaged 100 atomic veterans and 58 persons representative of the United States general population using the fission track analysis technique, developed by Brookhaven National Laboratory. The methodology, collected data, scientific challenges, and test results are presented herein. The Defense Threat Reduction Agency and its predecessor agencies conducted this program in the late 1990s to the mid-2000s to determine the feasibility of bioassay testing to supplement dose reconstruction to estimate atomic veterans' doses under the agency's Nuclear Test Personnel Review Program. In summary, Pu urine bioassay using fission track analysis showed inconsistencies in sample measurement repeatability. To use the analysis as a tool to enhance current processes to perform accurate dose reconstructions requires extensive understanding and resolution of the measurement inconsistencies well beyond the scope of this pilot study. Therefore, fission track analysis (FTA) was found not feasible for implementation on a wide scale basis for atomic veterans.

A rapid method for estimation of Pu-isotopes in urine samples using high volume centrifuge.

The conventional radio-analytical technique used for estimation of Pu-isotopes in urine samples involves anion exchange/TEVA column separation followed by alpha spectrometry. This sequence of analysis consumes nearly 3-4 days for completion. Many a times excreta analysis results are required urgently, particularly under repeat and incidental/emergency situations. Therefore, there is need to reduce the analysis time for the estimation of Pu-isotopes in bioassay samples. This paper gives the details of standardization of a rapid method for estimation of Pu-isotopes in urine samples using multi-purpose centrifuge, TEVA resin followed by alpha spectrometry. The rapid method involves oxidation of urine samples, co-precipitation of plutonium along with calcium phosphate followed by sample preparation using high volume centrifuge and separation of Pu using TEVA resin. Pu-fraction was electrodeposited and activity estimated using 236Pu tracer recovery by alpha spectrometry. Ten routine urine samples of radiation workers were analyzed and consistent radiochemical tracer recovery was obtained in the range 47-88% with a mean and standard deviation of 64.4% and 11.3% respectively. With this newly standardized technique, the whole analytical procedure is completed within 9h (one working day hour).

Interpretation of Urinary Excretion Data From Plutonium Wound Cases Treated With DTPA: Application of Different Models and Approaches.

After a chelation treatment, assessment of intake and doses is the primary concern of an internal dosimetrist. Using the urinary excretion data from two actual wound cases encountered at Los Alamos National Laboratory (LANL), this paper discusses several methods that can be used to interpret intakes from the urinary data collected after one or multiple chelation treatments. One of the methods uses only the data assumed to be unaffected by chelation (data collected beyond 100 d after the last treatment). This method, used by many facilities for official dose records, was implemented by employing maximum likelihood analysis and Bayesian analysis methods. The impacts of an improper assumption about the physicochemical behavior of a radioactive material and the importance of the use of a facility-specific biokinetic model when available have also been demonstrated. Another method analyzed both the affected and unaffected urinary data using an empirical urinary excretion model. This method, although case-specific, was useful in determining the actual intakes and the doses averted or the reduction in body burdens due to chelation treatments. This approach was important in determining the enhancement factors, the behavior of the chelate, and other observations that may be pertinent to several DTPA compartmental modeling approaches being conducted by the health physics community.