Plutonium Intake Research Articles

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

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.

Chelation Model Validation: Modeling of a Plutonium-238 Inhalation Incident Treated with DTPA at Los Alamos National Laboratory.

Accidental inhalation of plutonium at the workplace is a non-negligible risk, even when rigorous safety standards are in place. The intake and retention of plutonium in the human body may be a source of concern. Thus, if there is a suspicion of a significant intake of plutonium, medical countermeasures such as chelation treatment may be administered to the worker. The present work aimed to interpret the bioassay data of a worker involved in an inhalation incident due to a glovebox breach at Los Alamos National Laboratory's plutonium facility. The worker was treated with intravenous injections of calcium salts of diethylenetriaminepentaacetic acid (DTPA) in an attempt to reduce the amount of plutonium from the body and therefore reduce the internal radiation dose. It is well known in the internal dosimetry field that the administration of chelation treatment poses additional challenges to the dose assessment. Hence, a recently developed chelation model was used for the modeling of the bioassay data. The objectives of this work are to describe the incident, model the chelation-affected and non-affected bioassay data, estimate the plutonium intake, and assess the internal radiation dose.

МЕТОДОЛОГИЯ НОРМИРОВАНИЯ ВНУТРЕННЕГО ОБЛУЧЕНИЯ ОТ ПЛУТОНИЯ: ПРОБЛЕМЫ И ПУТИ РЕШЕНИЯ

Purpose: The presented materials are devoted to the development of a methodology for rationing the impact of plutonium intake by the amount of annual excess risk, which should not exceed 1 ×10-3. It is shown that the existing approach to the rationing of plutonium by the expected effective dose does not reflect the actual levels of personnel exposure and, therefore, does not provide the necessary level of radiation safety at plutonium processing plants. Results: Using data from epidemiological surveillance of a cohort of employees of the Mayak software, an assessment of the excessive relative risk per unit dose of radiation exposure for each of the plutonium-239 deposition organs was performed in order to describe the dependence of mortality from lung, liver and skeletal cancer on the dose of alpha radiation of plutonium-239. Equivalent doses to plutonium deposit organs and the annual excess risk generated by these doses for various plutonium intake scenarios are calculated based on the results of monitoring the activity of plutonium in urine. When calculating the annual effective dose based on the results of monitoring the annual equivalent dose, it is necessary to take into account the dependence of the weighing coefficients for the plutonium deposit bodies on the age of the employee at which the exposure occurred, and when assessing the magnitude of the radiation risk, the dependence of the risk coefficient on age. Conclusion: The use of the annual excess risk value as a controlled and normalized indicator for the individual dosimetry control of internal radiation from the plutonium intake is the most correct. The proposed approach to rationing can be used for acute and chronic inhalation intake of plutonium, as well as for the intake of plutonium through damaged skin.

Analysis of correspondence between the current individual monitoring system of internal exposure caused by plutonium intake and the relevant ICRP recommendations

Individual dosimetry monitoring of occupational internal exposure due to plutonium intake is performed by the bioassay method which measures the plutonium isotopes in daily urine samples. Then, to estimate normalized values (committed effective dose and intake), biokinetic and dosimetry models are used. The currently valid major instruments of radiation safety in the Russian Federation are based on the requirements and approaches outlined in Publications 68 and 78 of the International Commission on Radiobiological Protection. In implementing the requirements of Publication 130 there will be a need for updating the Russian guidance documents to the new requirements. The purpose of this study was the analysis of correspondence of the current system of individual monitoring of internal exposure caused by plutonium intake to the relevant recommendations of the International Commission on Radiobiological Protection outlined in Publication 130 by the example of the FSUE “Mayak PA” production conditions. As a result of the study, the values of annual limit of plutonium intake were determined based on new biokitetic and dosimetry models, and the measured values were calculated during the current dosimetry monitoring corresponding to the value of committed effective dose limit for Category A, B personnel and women under 45 years of age. It was found that following the introduction of new requirements of the International Commission on Radiobiological Protection for Type M compounds, an intake of more than 1/4 of annual limit of plutonium intake could be determined within a year after intake using the method of alpha spectrometry. To determine an intake of 1/20 of annual limit of intake at the recommended interval of 180 days between measurements, it is necessary to use inductively-coupled plasma mass spectrometry. For the personnel working with insoluble compounds of plutonium, an intake of one annual limit of intake and 1/4 of annual limit of intake can be determined using mass spectrometry, and 1/20 of annual limit of intake can be determined using only a more sensitive method.

Side Effects and Complications Associated with Treating Plutonium Intakes: A Retrospective Review of the Medical Records of LANL Employees Treated for Plutonium Intakes, with Supplementary Interviews.

Anecdotal evidence indicates there may be unpublished physical and psychological events associated with the medical treatment of plutonium intakes. A thorough review was conducted of the medical and bioassay records of current and previous Los Alamos National Laboratory (LANL) employees who had experienced plutonium intakes via wound or inhalation. After finding relatively incomplete information in the medical records, the research team interviewed current LANL employees who had undergone chelation therapy and/or surgical excision. Although the dataset is not large enough to reach statistically significant conclusions, it was observed that adverse events associated with treatment appear to be more frequent and more severe than previously reported.

Four-decade follow-up of a plutonium-contaminated puncture wound treated with Ca-DTPA

Contaminated wounds are a common route of internal deposition of radionuclides for nuclear and radiation workers. They may result in significant doses to radiosensitive organs and tissues in an exposed individual’s body. The United States Transuranium and Uranium Registries’ whole-body donor (Case 0303) accidentally punctured his finger on equipment contaminated with plutonium nitrate. The wound was surgically excised and medically treated with intravenous injections of Ca-DTPA. A total of 16 g Ca-DTPA was administered in 18 treatments during the 2 months following the accident. Ninety-three urine samples were collected and analysed over 14 years following the accident. An estimated 239Pu activity of 73.7 Bq was excreted during Ca-DTPA treatment. Post-mortem radiochemical analysis of autopsy tissues indicated that 40 years post-accident 21.6 ± 0.2 Bq of 239Pu was retained in the skeleton, 12.2 ± 0.3 Bq in the liver, and 3.7 ± 0.1 Bq in other soft tissues; 1.35 ± 0.02 Bq of 239Pu was measured in tissue samples from the wound site. To estimate the plutonium intake, late urine measurements, which were unaffected by chelation, and post-mortem radiochemical analysis results were evaluated using the IMBA Professional Plus software. The application of the National Council on Radiation Protection and Measurements wound model with an assumption of intake material as a predominantly strongly retained soluble plutonium compound with a small insoluble fraction adequately described the data (p = 0.46). The effective intake was estimated to be 50.2 Bq of plutonium nitrate and 1.5 Bq of the fragment. The prompt medical intervention with contaminated tissue excision and subsequent Ca-DTPA decorporation therapy reduced 239Pu activity available for uptake and long-term retention in this individual’s systemic organs by a factor of 38.

MODELING THE LONG-TERM RETENTION OF PLUTONIUM IN THE HUMAN RESPIRATORY TRACT USING SCAR-TISSUE COMPARTMENTS.

The respiratory tract tissues of four former nuclear workers with plutonium intakes were radiochemically analyzed post mortem by the United States Transuranium and Uranium Registries. Plutonium activities in the upper respiratory tract of these individuals were found to be higher than those predicted using the most recent biokinetic models described in publications of the International Commission on Radiological Protection. Modification of the model parameters, including the bound fraction, was not able to explain the data in one of the four individuals who had inhaled insoluble form of plutonium. Literature review points to the presence of-and a significant retention of-plutonium in the scar tissues of the lungs. Accordingly, an alternate model with scar-tissue compartments corresponding to larynx, bronchi, bronchioles, alveolar-interstitium and thoracic lymph nodes was proposed. The rates of transfer to the scar tissue compartments were determined using Markov Chain Monte Carlo analysis of data on urinary excretion, lung counts and post-mortem measurements of liver, skeleton and individual respiratory tract compartments, as available. The posterior models predicted that 20-100%-depending on the solubility of the material inhaled-of the activities retained in the respiratory tract were sequestered in the scar tissues.

РАСЧЕТ ДОЗЫ ВНУТРЕННЕГО ОБЛУЧЕНИЯ И ВОЗМОЖНЫЕ ВАРИАНТЫ НОРМИРОВАНИЯ ПРИ РАНЕВОМ ПОСТУПЛЕНИИ РАДИОНУКЛИДОВ ПЛУТОНИЯ

Purpose: Assessment of the degree of compliance with the principles of radiation safety and regulatory requirements in case of plutonium wounds. 
 Material and methods: Using a wound intake of plutonium by a worker as an example, issues of the formation of the internal dose due to the wound intake and formal comparison of calculated dose values with regulatory requirements are considered. The calculations are carried out using expert analysis of the experimental data on the urine excretion of plutonium during the observation period of 7 years based on the ICRP model for direct intake into blood. In addition, calculations are carried out using prognostic assessment of the same dose values based on the biokinetic model for radionuclide-contaminated wounds published by NCRP Report No 156 together with the above model of the ICRP for plutonium compounds Strong, Colloids, Particles and Fragment. 
 Results: Based on the calculations, possible annual limits on intakes (ALI) of radionuclides in case of plutonium wounds are derived. As criteria for determining the ALI, dose values were taken that due to the uptake of the radionuclide into the systemic circulation from the wound for any calendar year considered for 50 years after the wound intake of selected plutonium compound. Namely, the committed effective dose; the effective dose implemented in a year and the organ annual equivalent dose (to bone surface and liver). 
 Conclusion: Based on the analysis of the above calculations, the authors formulated the formation features of the employee’s internal exposure due to wound intake of plutonium and recommendations for determining the value of plutonium intake in the wound, evaluating the effectiveness of decorporation therapy and determining the type of radionuclide compound. This allows one to more accurately assess the degree of compliance with regulatory requirements and make an informed decision on the necessary measures of medical intervention and their urgency.

Mortality among Workers at the Los Alamos National Laboratory, 1943-2017

Background During World War II, the Manhattan Engineering District established a secret laboratory in the mountains of northern New Mexico. The mission was to design, construct and test the first atomic weapon, nicknamed “the Gadget” that was detonated at the TRINITY site in Alamogordo, NM. After WWII, nuclear weapons research continued, and the laboratory became the Los Alamos National Laboratory (LANL). Materials and methods The mortality experience of 26,328 workers first employed between 1943-1980 at LANL was determined through 2017. Included were 6,157 contract workers employed by the ZIA Company. Organ dose estimates for each worker considered all sources of exposure, notably photons, neutrons, tritium, 238Pu and 239Pu. Vital status determination included searches within the National Death Index, Social Security Administration and New Mexico State Mortality Files. Standardized Mortality Ratios (SMR) and Cox regression models were used in the analyses. Results Most workers (55%) were hired before 1960, 38% had a college degree, 25% were female, 81% white, 13% Hispanic and 60% had died. Vital status was complete, with only 0.1% lost to follow-up. The mean dose to the lung for the 17,053 workers monitored for radiation was 28.6 weighted-mGy (maximum 16.8 weighted-Gy) assuming a Dose Weighting Factor of 20 for alpha particle dose to lung. The Excess Relative Risk (ERR) at 100 weighted-mGy was 0.01 (95%CI -0.02, 0.03; n = 839) for lung cancer. The ERR at 100 mGy was -0.43 (95%CI -1.11, 0.24; n = 160) for leukemia other than chronic lymphocytic leukemia (CLL), -0.06 (95%CI -0.16, 0.04; n = 3,043) for ischemic heart disease (IHD), and 0.29 (95%CI 0.02, 0.55; n = 106) for esophageal cancer. Among the 6,499 workers with measurable intakes of plutonium, an increase in bone cancer (SMR 2.44; 95%CI 0.98,5.03; n = 7) was related to dose. The SMR for berylliosis was significantly high, based on 4 deaths. SMRs for Hispanic workers were significantly high for cancers of the stomach and liver, cirrhosis of the liver, non-malignant kidney disease and diabetes, but the excesses were not related to radiation dose. Conclusions There was little evidence that radiation increased the risk of lung cancer or leukemia. Esophageal cancer was associated with radiation, and plutonium intakes were linked to an increase of bone cancer. IHD was not associated with radiation dose. More precise evaluations will await the pooled analysis of workers with similar exposures such as at Rocky Flats, Savannah River and Hanford.

Development of a New Chelation Model: Bioassay Data Interpretation and Dose Assessment after Plutonium Intake Via Wound and Treatment with DTPA: Erratum.

Development of a New Chelation Model: Bioassay Data Interpretation and Dose Assessment after Plutonium Intake Via Wound and Treatment with DTPA: Erratum.

Development of a New Chelation Model: Bioassay Data Interpretation and Dose Assessment after Plutonium Intake via Wound and Treatment with DTPA

The administration of chelation therapy to treat significant intakes of actinides, such as plutonium, affects the actinide's normal biokinetics. In particular, it enhances the actinide's rate of excretion, such that the standard biokinetic models cannot be applied directly to the chelation-affected bioassay data in order to estimate the intake and assess the radiation dose. The present study proposes a new chelation model that can be applied to the chelation-affected bioassay data after plutonium intake via wound and treatment with DTPA. In the proposed model, chelation is assumed to occur in the blood, liver, and parts of the skeleton. Ten datasets, consisting of measurements of C-DTPA, Pu, and Pu involving humans given radiolabeled DTPA and humans occupationally exposed to plutonium via wound and treated with chelation therapy, were used for model development. The combined dataset consisted of daily and cumulative excretion (urine and feces), wound counts, measurements of excised tissue, blood, and post-mortem tissue analyses of liver and skeleton. The combined data were simultaneously fit using the chelation model linked with a plutonium systemic model, which was linked to an ad hoc wound model. The proposed chelation model was used for dose assessment of the wound cases used in this study.

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.

Molecular dynamics simulations of plutonium binding and its decorporation from the binding-cleft of human serum transferrin.

The possibility of plutonium (Pu) intake by radiation workers can not be ruled out. Transportation of Pu(IV) to various organs/cells is mainly carried through iron-carrying protein, serum transferrin (sTf), by receptor-mediated endocytosis. Understanding the Pu-sTf interaction is a primary step toward future design of its decorporating agents. We report MD simulations of Pu(IV) binding with sTf and look out for its decorporation at extracellular pH using suitable ligands. MD simulations were carried out in polarizable water environment at different protonation states of the protein. Results unravel the binding motif of Pu(IV): (1) sTf binds the ion in closed conformation at extracellular serum pH with carbonate as synergistic anions, (2) change in protonation state of dilysine (K206 and K296)-trigger and that of the carbonate ion at acidic endosomal pH is found to cause conformational changes of protein, conducive for the heavy ion to be released, although; (3) strong electrostatic interaction between D63 in the binding-cleft and Pu(IV) is found not to ever set free the ion. In an endeavour to decorporate Pu(IV), fragmented molecular form of hydroxypyridinone (HOPO) and catechol (CAM)-based ligands are docked at the binding site (BS) of the protein and metadynamics simulations are conducted. Pu(IV) binding at BS is found to be so strong that it was not detached from BS with the docked HOPO. However, for the identical set of simulation parameters, CAM is found to facilitate dislodging the heavy ion from the protein's binding influence. Differential behaviour of the two chelators is further explored. Fragmented molecular form of hydroxy-pyridinone (HOPO) and catecholamide (CAM) ligands were docked at the binding-site (BS) of human serum transferrin (sTf) to explore their feasibility as plausible Pu(IV) decorporating agents by employing metadynamics method. CAM was found to dislodge Pu from the sTf BS, while HOPO could not.

Report of the Japan Health Physics Society ad hoc working group for the Plutonium intake accident**An original WG report was published in Jpn J Health Physics, 53(4).271-281 (2018). ‘JHPS Working Group for Plutonium Accident in JAEA-Oarai, Satoshi IWAI, Michiya SASAKI, Shogo HIGAKI, Hirokuni YAMANISHI and Michiaki KAI’ (in Japanese). To share the original report, it has been translated into English

This paper describes an overview of the radiation protection response to the Plutonium intake accident that occurred at the Plutonium Fuel Facility of the Oarai Research and Development Center of the Japan Atomic Energy Agency on 6 June 2017. In the hood of the analyzing room at the Plutonium Fuel Facility five workers were checking a storage container of fast reactor nuclear fuel material. Around 11:15 a.m., vinyl bags inside the fuel material container containing Plutonium and enriched uranium burst during the inspection work. All the workers heard the bang, which caused misty dust leakage from the container. This event caused significant both skin and nasal α-contamination for three workers and just skin α-contamination for one worker. Decontamination was conducted in the shower room. Then the five workers were transferred to the Nuclear Fuel Cycle Engineering Laboratory to evaluate inhalation intake of Plutonium etc in the lungs. The maximum values of 2.2 × 104 Bq for 239Pu and 2.2 × 102 Bq for 241Am were estimated by the lung monitor. Based on these results, injection of a chelate agent was conducted for prompt excretion of Plutonium etc. The next morning, the five workers were transferred to the National Institute of Radiological Sciences for treatment including decontamination of their skin and measurement by a lung monitor. At that time no obvious energy peak was confirmed for Plutonium. The Japan Health Physics Society launched an ad-hoc working group for Plutonium intake accident around the middle of June to survey issues and to extract lessons for radiological protection. The authors, who are the members of the ad-hoc working group, here report the activity of the working group.

Estimation of Total Skeletal Content of Plutonium and 241Am From Analysis of a Single Bone.

The skeleton is one of the major retention sites for internally deposited actinides. Thus, an accurate estimation of the total skeleton content of these elements is important for biokinetic modeling and internal radiation dose assessment. Data from 18 whole-body donations to the US Transuranium and Uranium Registries with known plutonium intakes were used to develop a simple and reliable method for estimation of plutonium and Am activity in the total skeleton from single-bone analysis. A coefficient of deposition Kdep, defined as the ratio of actinide content in the patella to that in the skeleton, was calculated for Pu, Pu, and Am. No statistical difference was found in Kdep values among these radionuclides. Variability in Kdep values was investigated with relation to skeleton pathology (osteoporosis). The average Kdep of 0.0051 ± 0.0009 for the osteoporotic group was statistically different from Kdep of 0.0032 ± 0.0010 for nonosteoporotic individuals. The use of Kdep allows for rapid estimation of the total skeletal content of plutonium and Am with up to 35% uncertainty. To improve accuracy and precision of total skeleton activity estimates, regression analysis with power function was applied to the data. Strong correlation (r > 0.9) was found between Pu, Pu, and Am activities measured in the patella bone and total skeleton activity. The results of this study are specifically important for the optimization of bone sample collection for US Transuranium and Uranium Registries partial-body donations.

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.

Report of the JHPS Working Group for Plutonium Intake Accident

Report of the JHPS Working Group for Plutonium Intake Accident

The Mayak Worker Dosimetry System (MWDS-2013): Uncertainty in the Measurement of Pu Activity in a 24-Hour Urine Sample of a Typical Mayak PA Worker.

In the Mayak Worker Dosimetry System (MWDS-2013), intakes of plutonium and organ doses are assessed on the basis of measurements made on the plutonium content of 56400 urine samples. Altogether, there were urine bioassays for 7591 (29%) of the 25757 cohort members who were employed any time at Mayak between 1948 and 1982. These measurements are subject to uncertainty due to many factors (e.g. whether or not creatinine is measured, the volume of the sample, whether diethylenetriaminepentaacetic acid was administered, etc.) and this uncertainty will affect not only the uncertainty in the estimated doses, but also the values of the doses themselves. Therefore, it is important for the estimated uncertainty to be as accurate as possible. The input to the dose calculation requires an estimate of the plutonium activity in a true 24-hour sample. The uncertainty in this activity is approximated by a lognormal distribution. The aim of this paper is to describe and justify how the parameters of this lognormal distribution are derived from the raw data. Histograms of the distribution of sample volumes are given for both sexes. The method of calculation of the decision threshold and relative standard uncertainty (RSU) of a measurement result for Pu activity in a worker's urine sample is shown. Diagrams of correlation between Pu activity in collected urine and its RSU are given.

THE MAYAK WORKER DOSIMETRY SYTEM (MWDS-2013): DETERMINATION OF THE INDIVIDUAL SCENARIO OF INHALED PLUTONIUM INTAKE IN THE MAYAK WORKERS.

In order to estimate doses of workers exposed to plutonium, it is necessary to make assumptions about both the route and the time course of intake. The objective of this study was to determine a time course for the inhalation rate for plutonium (intake regime) useful for biokinetic modeling. Records from workplace air sampling, personnel biophysical examinations and autopsy data from former Mayak Production Association (MPA) workers were used. Plutonium accumulation strongly correlated with the volumetric activity of plutonium in workplace air. Using data from activity in air at MPA workplaces over time, a three-step function of intake was adopted. The adequacy of this three-step function was tested by comparing predicted doses using more complicated intake regimes. Uncertainties on the three-step function were also characterized based on air sampling data. The three-step function was assumed to be common to all workers, but an individual intake regime for each worker was calculated by convoluting it with the worker's actual employment history.

In vitro assessment of plutonium uptake and release using the human macrophage-like THP-1 cells

Plutonium (Pu) intake by inhalation is one of the major potential consequences following an accident in the nuclear industry or after improvised nuclear device explosion. Macrophages are essential players in retention and clearance of inhaled compounds. However, the extent to which these phagocytic cells are involved in these processes highly depends on the solubility properties of the Pu deposited in the lungs. Our objectives were to develop an in vitro model representative of the human pulmonary macrophage capacity to internalize and release Pu compounds in presence or not of the chelating drug diethylenetriaminepentaacetate (DTPA).The monocyte cell line THP-1 was used after differentiation into macrophage-like cells. We assessed the cellular uptake of various forms of Pu which differ in their solubility, as well as the release of the internalized Pu. Results obtained with differentiated THP-1 cells are in good agreement with data from rat alveolar macrophages and fit well with in vivo data. In both cell types, Pu uptake and release depend upon Pu solubility and in all cases DTPA increases Pu release.The proposed model may provide a good complement to in vivo animal experiments and could be used in a first assessment to predict the fraction of Pu that could be potentially trapped, as well as the fraction available to chelating drugs.