Melinda P. Krahenbuhl

Mayak Worker Study: An Improved Biokinetic Model for Reconstructing Doses from Internally Deposited Plutonium

Abstract Leggett, R. W., Eckerman, K. F., Khokhryakov, V. F., Suslova, K. G., Krahenbuhl, M. P. and Miller, S. C. Mayak Worker Study: An Improved Biokinetic Model for Reconstructing Doses from Internally Deposited Plutonium. Radiat. Res. 164, 111–122 (2005). The plutonium production facility known as the Mayak Production Association was put into operation in June 1948. A high incidence of cancer in the Mayak workers has been related to the level of exposure to plutonium, but uncertainties in tissue doses have hampered development of dose–risk relationships. As part of an effort to improve dose estimates for these workers, the systemic biokinetic model for plutonium currently recommended by the International Commission on Radiological Protection (ICRP) has been modified to reflect recently developed data and facilitate interpretation of case-specific information. This paper describes the proposed model and discusses its implications for dose reconstruction for the Mayak workers.

Mayak worker dosimetry study : An overview

The Mayak Production Association (MPA) was the first plutonium production plant in the former Soviet Union. Workers at the MPA were exposed to relatively large internal radiation intakes and external radiation exposures, particularly in the early years of plant operations. This paper describes the updated dosimetry database, “Doses-2005.” Doses-2005 represents a significant improvement in the determination of absorbed organ dose from external radiation and plutonium intake for the original cohort of 18,831 Mayak workers. The methods of dose reconstruction of absorbed organ doses from external radiation uses: 1) archive records of measured dose and worker exposure history, 2) measured energy and directional response characteristics of historical Mayak film dosimeters, and 3) calculated dose conversion factors for Mayak Study-defined exposure scenarios using Monte Carlo techniques. The methods of dose reconstruction for plutonium intake uses two revised models developed from empirical data derived from bioassay and autopsy cases and/or updates from prevailing or emerging International Commission on Radiological Protection models. Other sources of potential significant exposure to workers such as medical diagnostic x-rays, ambient onsite external radiation, neutron radiation, intake of airborne effluent, and intake of nuclides other than plutonium were evaluated to determine their impact on the dose estimates.

Development of an improved dosimetry system for the workers at the Mayak Production Association

Databases are being created that contain verified and updated dosimetry and worker history information for workers at the Mayak Production Association. Many workers had significant external and internal exposures, particularly during the early years (1948-1952) of operation. These dosimetric and worker history data are to be used in companion epidemiology studies of stochastic and deterministic effects. The database contains both external and internal dose information and is being constructed from other databases that include radiochemical analyses of tissues, bioassay data, air sampling data, whole body counting data, and occupational and worker histories. The procedures, models, methods, and operational uncertainties will be documented and included in the database, technical reports, and publications. The cohort of the stochastic epidemiological study is expected to include about 19,000 persons while the cohort for the deterministic epidemiological study is expected to include about 600 persons. For external dosimetry, workplace gamma, beta, and neutron doses are being reconstructed. The models used for this incorporate issues such as known isotopes, composition, shielding, further analysis of film badge sensitivities, and records of direct measurements. Organ doses from external exposures are also being calculated. Methods for calculating dose uncertainties are being developed. For internal dosimetry, the organ doses have been calculated using the established FIB-1 biokinetic model. A new biokinetic model is being developed that includes more information of the solubility and biokinetics of the different chemical forms and particulate sizes of plutonium that were in the workplace. In addition, updated worker histories will be used to estimate doses to some workers where direct measurements were not made. A rigorous quality control procedure is being implemented to ensure that the correct dosimetry data is entering the various databases being used by the epidemiologists.

Adaptation of the ICRP publication 66 respiratory tract model to data on plutonium biokinetics for Mayak workers

The biokinetics of inhaled plutonium were analyzed using compartment models representing their behavior within the respiratory tract, the gastrointestinal tract, and in systemic tissues. The processes of aerosol deposition, particle transport, absorption, and formation of a fixed deposit in the respiratory tract were formulated in the framework of the Human Respiratory Tract Model described in ICRP Publication 66. The values of parameters governing absorption and formation of the fixed deposit were established by fitting the model to the observations in 530 autopsy cases. The influence of smoking on mechanical clearance of deposited plutonium activity was considered. The dependence of absorption on the aerosol transportability, as estimated by in vitro methods (dialysis), was demonstrated. The results of this study were compared to those obtained from an earlier model of plutonium behavior in the respiratory tract, which was based on the same set of autopsy data. That model did not address the early phases of respiratory clearance and hence underestimated the committed lung dose by about 25% for plutonium oxides. Little difference in lung dose was found for nitrate forms.

Extrapulmonary organ distribution of plutonium in healthy workers exposed by chronic inhalation at the Mayak production association.

The systemic distribution of plutonium was determined for “healthy” workers who chronically inhaled plutonium at the radiochemical plants of the Mayak Production Association. The data were obtained by radiochemical analysis of soft tissues and bones samples collected upon autopsy of 120 workers who died from acute coronary diseases and accidents. The soft tissue samples were wet-ashed using nitric acid and hydrogen peroxide. Bone samples were ashed in a muffle furnace at 500°C. Plutonium was extracted on anionite and coprecipitated with bismuth phosphate. The precipitation was blended with ZnS powder, and the alpha-activity was measured by ZnS solid scintillation counting in a low-background alpha radiometer. Twenty-five years after the beginning of inhalation exposures, the average percentage of plutonium in the skeleton and liver was 50% and 42% of systemic burden, respectively. A multivariate regression was used to quantify the effects of exposure time, “transportability” of the various compounds, plutonium body content, and age on systemic plutonium distribution. The early retention of plutonium in the liver is assumed to be greater than that in the skeleton. The initial distribution of plutonium between the liver and the skeleton, immediately after entering the circulatory system, was 50:38%, respectively. With time, the fraction of plutonium found in the liver decreased, while the fraction in the skeleton increased at a rate of 0.5% y−1 of systemic deposition. Exposure time had a greater effect on the relative retention of plutonium in the main organs when compared to age. The statistical estimates that characterized the relative plutonium distribution were less stable for the liver than for the skeleton, likely due to the slower turnover of skeletal tissues and the retention of plutonium in bone.

Comparisons of the Skeletal Locations of Putative Plutonium-Induced Osteosarcomas in Humans with those in Beagle Dogs and with Naturally Occurring Tumors in both Species

Abstract Miller, S. C., Lloyd, R. D., Bruenger, F. W., Krahenbuhl, M. P. and Romanov, S. A. Comparisons of the Skeletal Locations of Putative Plutonium-Induced Osteosarcomas in Humans with those in Beagle Dogs and with Naturally Occurring Tumors in both Species. Radiat. Res. 160, 517–523 (2003). Osteosarcomas occur from exposures to bone-seeking, α-particle-emitting isotopes, particularly plutonium. The skeletal distribution of putative 239Pu-induced osteosarcomas reported in Mayak Metallurgical and Radiochemical Plutonium Plant workers is compared with those observed in canine studies, and these are compared with distributions of naturally occurring osteosarcomas in both species. In the Mayak workers, 29% and 71% of the osteosarcomas were in the peripheral and central skeleton, respectively, with the spine having the most tumors (36%). An almost identical distribution of plutonium-induced osteosarcomas was reported for dogs injected with 239Pu as young adults. This distribution of osteosarcomas is quite different from the distributions of naturally occurring osteosarcomas for both species. In the Cooperative Osteosarcoma Study Group in humans (1,736 osteosarcomas from all ages), over 91% of the tumors occurred in the peripheral skeleton. In the Mayo Clinic group of older individuals (>40 years old), over 60% of the osteosarcomas appeared in the peripheral skeleton. The distribution of naturally occurring osteosarcomas in the canine is similar to that in the adult human. The similarities of the distributions of plutonium-associated osteosarcomas in the Mayak workers with those found in experimental studies suggest that many of the reported osteosarcomas may have been associated with plutonium exposures. These results also support the experimental paradigm that plutonium osteosarcomas have a preference for well vascularized cancellous bone sites. These sites have a greater initial deposition of plutonium, but also greater turnover due to elevated bone remodeling rates.

The development of the plutonium lung clearance model for exposure estimation of the Mayak production association, nuclear plant workers.

The purpose of this study was to develop a biokinetic model that uses urinary plutonium excretion rate data to estimate the plutonium accumulation in the human respiratory tract after occupational exposure. The model is based on autopsy and urinalysis data, specifically the plutonium distribution between the respiratory tract and the remainder of the body, taken from 543 former workers of a radiochemical facility at the Mayak Production Association (MPA) plant. The metabolism of plutonium was represented with a compartmental model, which considers individual exposure histories and the inherent solubility properties of industrial plutonium aerosols. The transport properties of plutonium-containing aerosols were estimated by experimentally defining their in vitro solubility. The in vitro solubilities were found by dialysis in a Ringer’s solution. Analysis of the autopsy data indicated that a considerable fraction of the inhaled plutonium is systemically redistributed rapidly after inhalation. After the initial dynamic period, a three-compartment model describes the retention in the respiratory tract. One compartment describes the nuclide retained in the lungs, the second compartment describes a plutonium lung concentration that exponentially decreases with time, and the third compartment describes the concentration in the pulmonary lymph nodes. The model parameters were estimated by minimizing sum squared of the error between the tissue and bioassay data and the model results. The parameters reflect the inverse relationship between plutonium retention in lungs and the experimentally derived aerosol transportability. The model was validated by comparing the autopsy results with in vivo data for 347 cases. The validation indicates that the model parameters are unbiased. This model is being used to estimate individual levels of nuclide accumulation and to compute radiation doses based upon the urinary excretion rates.

Uncertainties analysis for the plutonium dosimetry model, doses-2005, using Mayak bioassay data.

The Doses-2005 model is a combination of the International Commission on Radiological Protection (ICRP) models modified using data from the Mayak Production Association cohort. Surrogate doses from inhaled plutonium can be assigned to approximately 29% of the Mayak workers using their urine bioassay measurements and other history records. The purpose of this study was to quantify and qualify the uncertainties in the estimates for radiation doses calculated with the Doses-2005 model by using Monte Carlo methods and perturbation theory. The average uncertainty in the yearly dose estimates for most organs was approximately 100% regardless of the transportability classification. The relative source of the uncertainties comes from three main sources: 45% from the urine bioassay measurements, 29% from the Doses-2005 model parameters, and 26% from the reference masses for the organs. The most significant reduction in the overall dose uncertainties would result from improved methods in bioassay measurement with additional improvements generated through further model refinement. Additional uncertainties were determined for dose estimates resulting from changes in the transportability classification and the smoking toggle. A comparison was performed to determine the effect of using the model with data from either urine bioassay or autopsy data; no direct correlation could be established. Analysis of the model using autopsy data and incorporation of results from other research efforts that have utilized plutonium ICRP models could improve the Doses-2005 model and reduce the overall uncertainty in the dose estimates.

The historical and current application of the FIB-1 model to assess organ dose from plutonium intakes in Mayak workers.

One of the objectives of the Joint Coordinating Committee for Radiation Effects Research Project 2.4 is to document the methodology used to determine the radiation doses in workers from the Mayak Production Association who were exposed to plutonium. The doses have been employed in numerous dose response studies measuring both stochastic and deterministic effects. This article documents both the historical (pre-1999) and current (“Doses 1999”) methods used by the FIB-1 scientists to determine the doses. Both methods are based on a three-chamber lung model developed by the FIB-1 scientists. This method was developed in partial isolation from the West and has unique characteristics from the more familiar ICRP biokinetic models. Some of these characteristics are the use of empirically based transportability classifications and the parameter modification for chelation-therapy-enhanced excretion data. An example dose calculation is provided and compared to the dose that would be obtained if the ICRP models were used. The comparison demonstrates that the models are not interchangeable and produce different results.

Modifying effects of health status, physiological, and dosimetric factors on extrapulmonary organ distribution and excretion of inhaled plutonium in workers at the Mayak Production Association.

This paper summarizes the systemic organ distribution of plutonium in workers exposed by chronic inhalation at the Mayak Production Association (MPA). Using results of radiochemical measurements in soft tissue and bone samples collected at autopsy of 853 autopsy cases, this paper provides data on the effects of various chronic diseases and malignant tumors as well as exposure time, age, sex, and body burden on systemic retention of plutonium in 22 extrapulmonary organs and on the urinary excretion rate of the nuclide. Some aspects of this work have been reported already. The results of present autopsy studies showed that liver pathology accompanied by strong fatty dystrophy of hepatocytes results in a significant relative decrease in the fraction of systemic plutonium in the liver and contravariant increase in the skeletal fraction. The average fractions of systemic plutonium in the liver and the skeleton of those MPA workers were 15% and 75%, respectively, in comparison with 47% and 45% in healthy individuals. Some of the plutonium also redistributed from the liver via blood to other systemic soft tissues. Plutonium not redistributed was excreted with urine. The results of multivariate regression analysis indicated some time-related and sex-related changes not connected with pathology for the liver and the skeleton retention fractions and excretion rate of plutonium. The current ICRP biokinetic models do not account for the influence of different pathological processes in the body on plutonium distribution in systemic organs and urinary excretion. This could have significant consequences for dosimetry calculations and risk estimations.