Modeling Plutonium Decorporation in a Female Nuclear Worker Treated with Ca-DTPA after Inhalation Intake.

ABSTRACT: The present work models plutonium (Pu) biokinetics in a female former nuclear worker. Her bioassay measurements are available at the US 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, fecal and urine samples were collected and analyzed for 239Pu and 241Am. Subsequently, she was followed up for bioassay monitoring over 14 y, with additional post-treatment urine samples collected and analyzed for 239Pu. The uniqueness of this dataset is due to the availability of: (1) both early and long-term bioassay data from a female with plutonium intake; (2) data on chelation therapy for a female; and (3) fecal measurement results. Chelation therapy with Ca- and/or Zn-salts of DTPA is known to aid in reducing the internal radiation dose by enhancing the excretion of plutonium and americium from the body. Such enhancement affects plutonium biokinetics in the human body, posing a challenge to the internal dose assessment. The current radiation dose assessment practice is to exclude the data affected by Ca-DTPA from the analysis. The present analysis is the first to explicitly model the chelation-affected bioassay data in a female by using a newly developed chelation model. Thus, the bioassay data collected during and after the Ca-DTPA administrations were used for biokinetic modeling and dose assessment. The Markov Chain Monte Carlo method was used to investigate model parameter uncertainty, based on the bioassay data and assumed prior probability distributions. A χ2/nData (number of data points) ≈ 1 was observed in this study, which indicates self-consistency of the data with the model. Results of this study show that the worker's 239Pu intake was 12 Bq, with a committed effective dose to the whole-body of 1.2 mSv and a committed equivalent dose to the bone surfaces, liver, and lungs of 37.8, 9.1, and 0.8 mSv, respectively. This study also discusses the worker's dose reduction due to chelation treatment.

Americium Systemic Biokinetic Model for Rats.

In this work, a baseline compartmental model of the distribution and retention of americium in the rat for a systemic intake was derived. The model was derived from data obtained from a study designed to evaluate the behavior of americium in the first 28 days after incorporation. A pharmacokinetic (PK)-front-end modeling approach was used to specify transfer to and from the extracellular fluids (ECF) in the various tissues in terms of vascular flow and volumes of ECF. Back-end rates representing transport into and out of the cells were determined empirically. Uncertainties in transfer rates were investigated using Markov chain Monte Carlo (MCMC). The combination of PK-front-end model and the back-end model structure used allowed for extrapolation to the earliest times with small uncertainty. This approach clearly demonstrated the rapid transfer of material from ECF to liver and bone. This model provides a baseline for modeling the action of decorporation agents, such as DTPA.

Biokinetics of 90Sr in Male Nonhuman Primates.

The current study tests the hypothesis that the biokinetics of Sr can be represented by simplification of the ICRP publication 78 Sr model. Default and proposed models were evaluated by their ability to predict injected activity and more thoroughly define the activity residing in the skeleton of rhesus monkeys. The data obtained from studies done by Patricia Durbin and her colleagues at the Lawrence Berkley National Laboratory were used to create a profile of the activity residing in the skeleton at the time of sacrifice. Post mortem data along with periodic whole body count data were used to optimize the biokinetic parameters using the Integrated Modules for Bioassay Analysis (IMBA), Weighted Likelihood Monte-Carlo Sampling (WeLMoS) program to better predict the intake and fit of the bioassay data. Analysis of the default ICRP 78 parameters resulted in an overprediction of activity in the skeleton for a male cohort by as much as 180%. Using Monte Carlo sampling methods, three models were developed and optimized for a composite cohort of male monkeys. Of the three developed models, one model proved to have the best predictive capabilities. The optimized model C obtained for the male cohort was then tested on a validation cohort to test predictive capabilities. Using the optimized model C parameters, the ability to predict activity in the skeleton was improved in comparison to ICRP 78. Prediction of the intake from bioassay data was also improved by a factor of 2 in comparison to ICRP 78. The results suggest that the modified transfer rates of model C could be used as default parameters for biokinetic nonhuman primate modeling and potentially extrapolated to humans.