Dynamics of body burdens and doses due to internal irradiation from intakes of long-lived radionuclides by residents of Ozyorsk situated near Mayak PA.

This paper presents and discusses new autopsy results and other historic data from earlier autopsies and environmental monitoring linked to releases from the Mayak PA facilities in the Chelyabinsk oblast in the southern Urals. The focus is on residents of the town of Ozyorsk located near to Mayak PA and the dynamics of body burdens and radiation doses from inhalation of plutonium alpha and americium-241, and ingestion of strontium-90 and caesium-137. It is demonstrated that accumulation and exposure from these radionuclides was mainly due to unplanned releases in the 1950s and 60s. The mean content of plutonium alpha at the time of autopsy of people commencing residence in Ozyorsk from 1949 to 1959 was about 3.5 Bq, falling to 0.2 Bq in those arriving after 1990. A reducing trend was also seen for (241)Am. The highest (90)Sr content in Ozyorsk residents was measured in 1967. The (137)Cs body content of residents arriving in Ozyorsk at any time was in almost all cases below the limit of detection. The committed effective dose from internal exposure to these long-lived radionuclides which would have been accumulated in Ozyorsk residents if present from 1949 to 2013 is estimated to be 13 mSv. This dose is primarily attributed to intakes during 1949 to 1959 when the annual effective dose rate was approximately 1 mSv y(-1). The current value is about 0.1 mSv y(-1). This dose is about 20 times higher than the dose from global man-made fallout, which is about 0.005 mSv y(-1) at present, but much lower than that from natural background radiation, i.e. about 2 mSv y(-1). The experience gained from this work and continuing activities can contribute to the development of improved international guidance in legacy situations, particularly as regards the provision and use of monitoring data to test and thereby build confidence in prognostic models for radiation conditions and potential future exposures. The scope includes evidence for the rate of reduction in radionuclide concentrations in environmental media and in their bioavailability, resuspension of long-lived alpha radionuclides, uptake of (90)Sr and (137)Cs in the food-chain, and confirmation of cumulative uptake via autopsy and whole body counting measurements. Continuing investigations will thus support decisions on future planned releases and contribute to planning of remediation of other areas affected by historic releases.

The effects of smoking and lung health on the organ retention of different plutonium compounds in the Mayak PA workers.

The purpose of this study was to determine the effects of smoking and lung health on the pulmonary and extrapulmonary retention after inhalation of different chemical forms of plutonium with different solubilities in workers from the Mayak Production Association (Ozersk, Russia). Samples of lung, pulmonary lymph nodes, liver and skeleton were obtained from 800 workers who died between 1962-2000. The chemical form of plutonium aerosols, smoking history and presence of lung disease were determined. In workers with normal lung status, all plutonium chemical classes were about equally distributed between the lung parenchyma and pulmonary lymph nodes. The more insoluble chemical forms of plutonium had a greater retention in pulmonary than systemic tissues regardless of smoking history or lung health status. A history of smoking did, however, result in a significantly greater retention of less soluble chemical forms of plutonium in pulmonary tissues of workers with no lung disease. In workers with lung disease, smoking did not significantly influence the terminal organ retention of the different chemical forms of plutonium. These initial data can be used to modify dosimetry and biokinetics models used for estimating radiation risks from plutonium in humans.

Plutonium in the Ozyorsk population.

Results of the long-term autopsy studies on plutonium body burden in the population of Ozyorsk situated in the vicinity of the radiochemical plant of the Mayak Production Association (Russia) have been presented. The data were obtained from radiochemical analysis of the soft tissue and bone samples collected at the autopsy of 239 non-occupational individuals for the period 1975-2003. The dynamics of plutonium accumulation in the Ozyorsk population is associated with the environmental contamination due to radioactive releases from the Mayak Production Association. Plutonium body burden and its distribution between the respiratory tract and extrapulmonary organs depend on the residence time of individuals in the city. Since the early 1950s, plutonium body burden in the Ozyorsk population was linearly increasing at the almost constant rate of accumulation and amounted to 5.8 Bq at 35 y after the beginning of residence in the city that was several tens of times higher than background levels of fallout plutonium. Distribution of plutonium in the body was also studied in Ozyorsk population. Plutonium deposition fraction in the respiratory tract did not exceed 11% of the body burden in individuals with short residence times (1-9 y) and is halved for increasing residence times more than 10 y. The average skeleton:liver ratio was 65:20 = 3.25.

In vitro dissolution study of plutonium in aerosol particles from the Mayak PA: a tool for individualised dose estimates.

Chronic inhalation of Pu particles during Mayak processing is a potential concern for workers. Of the many particle properties that affect individualised dose estimates, particle solubility in lung fluids can be most important. This study compares in vitro dissolution rates of several plutonium industrial compounds present at different stages of the Mayak processing cycle using three different solvents. The results are then used to develop values of absorption parameters for individual dose assessments. In this study, the dissolution rates of nitrate, oxide and mixed plutonium aerosols were determined using a serum ultrafiltrate stimulant (SUF), phagolysosomal simulant fluid and Ringer's solution, all using a static system. According to the results obtained with SUF, Pu nitrate is absorbed into the blood to a larger extent than predicted using model parameters currently applied for Mayak workers. Absorption into the blood of 21.5 vs. 3% of deposited nuclide as current model predicts results in underestimation of systemic burden and overestimation of the lung dose. These data are being used to provide improved retrospective dose assessments for inhaled plutonium aerosols.

Comparison of dose estimation from occupational exposure to 239Pu using different modelling approaches.

Several approaches are available for bioassay interpretation when assigning Pu doses to Mayak workers. First, a conventional approach is to apply ICRP models per se. An alternative method involves individualised fitting of bioassay data using Bayesian statistical methods. A third approach is to develop an independent dosimetry system for Mayak workers by adapting ICRP models using a dataset of available bioassay measurements for this population. Thus, a dataset of 42 former Mayak workers, who died of non-radiation effects, with both urine bioassay and post-mortem tissue data was used to test these three approaches. All three approaches proved to be adequate for bioassay and tissue interpretation, and thus for Pu dose reconstruction purposes. However, large discrepancies are observed in the resulting quantitative dose estimates. These discrepancies can, in large part, be explained by differences in the interpretation of Pu behaviour in the lungs in the context of ICRP lung model. Thus, a careful validation of Pu lung dosimetry model is needed in Mayak worker dosimetry systems.

The Mayak Worker Dosimetry System (MWDS-2013): Estimate of Pu Content in Lungs and Thoracic Lymph Nodes From a Limited Set of Organ Autopsy Samples.

A method to estimate plutonium content from a limited number of samples of lungs and pulmonary lymph nodes obtained at autopsies of former Mayak Production Association (MPA) workers is described. Historically from one to five samples of lung lobes and one to three respiratory lymph nodes (bronchopulmonary, tracheobronchial and paratracheal) were collected. The samples were used to estimate organ plutonium contents for cases where incomplete sets of samples were obtained, i.e. one to four lung lobes and one to two lymph nodes. This method was developed and validated using individual measurement data from 259 MPA autopsy cases with complete lung samples (five lobes) and three lymph nodes. A good correlation of plutonium content in measurements of two and four lung samples with the content estimate by five lung samples was obtained. The correlations with the individual lymph nodes were less robust than with the lung. The data are used to develop biokinetic, dosimetry and risk models for humans exposed to plutonium.

The Mayak Worker Dosimetry System (Mwds-2013): Plutonium Dissolution in The Lungs-An Analysis of Mayak Workers.

Lung doses resulting from inhalation of plutonium aerosols are highly dependent on the assumed rate of particle clearance, which occurs by two competing processes: (1) particle transport clearance to the alimentary tract and to the thoracic lymph nodes and (2) clearance to systemic tissues, which occurs by dissolution of particles in lung fluid followed by uptake to blood, which is a process collectively known as absorption. Unbiased and accurate estimates of the values of lung absorption parameters are required to obtain reliable estimates of lung dose, particularly those inferred from urine bioassay. Parameter values governing the rate of absorption are best estimated from data, such as autopsy measurements of plutonium in the lungs and systemic tissues, which directly relate to the exposed workers of interest. However, because the mathematical models that determine clearance from the lungs and systemic tissues are complex and consist of many parameters, estimates of model parameter values are subject to significant uncertainties. With this in mind, this paper uses a Bayesian approach to estimate one of the most important dissolution parameters: the slow rate of dissolution. This is estimated for both plutonium nitrate and plutonium oxide bearing aerosols in the lungs of former workers of the Mayak Production Association. A value of 2.6 × 10-4 d-1 is estimated for plutonium nitrates, and 4.7 × 10-5 d-1 for plutonium oxides.

The MAYAK WORKER DOSIMETRY SYSTEM (MWDS-2013): ESTIMATION OF PLUTONIUM SKELETAL BURDEN FROM LIMITED AUTOPSY BONE SAMPLES FROM MAYAK PA WORKERS.

The method to estimate total skeleton plutonium burden of former Mayak Production Association (MPA) workers from limited bone samples obtained at autopsy is described. From two to nine bone samples were obtained at autopsies conducted from the mid-1950s to 2013. Plutonium was measured using alpha-radiometry up to 2000 and later by alpha-spectrometry. The method was validated using data from whole-body donations from the United States Transuranium and Uranium Registries (USTUR). The developed algorithm overestimated the USTUR values from 20 to 40%, that is quite acceptable for conservative estimation. Late-in-life liver diseases known to redistribute plutonium between liver and skeleton were not associated with significant differences in plutonium deposition among sampled bones, except for the pelvis. Sources of uncertainties are discussed and future studies will address the reduction of these uncertainties. This algorithm can be used to obtain data in support of the development of biokinetic, dosimetric and risk models for humans exposed to plutonium.

The Mayak Worker Dosimetry System (MWDS-2013): A Comparison of Intakes Based on Urine Versus Autopsy Data From Mayak Workers Using the Leggett Systemic Model for Plutonium.

The Mayak Worker Dosimetry System-2013 (MWDS-2013) uses a model developed by Leggett and colleagues to represent the biokinetic behaviour of plutonium after uptake to blood. Of particular importance, with regard to estimating intakes (and doses), is the distribution of activity between urine and body organs (particularly liver and skeleton). In this study, measurement data (urine and autopsy) from around 500 Mayak workers have been used to validate use of this model. A robust method has been developed and used to estimate intakes from both urine and autopsy data separately, and the ratio of these estimates has been calculated for each worker. The geometric mean ratio has been shown to lie within a range of 0.92-1.14, depending on assumptions made. Since this range includes 1, the hypothesis that the model is unbiased with regard to estimating intakes either with urine or autopsy data cannot be rejected on the basis of these data. This lends weight to the argument for increasing the MWDS-2013 cohort to include an additional 500 workers for whom only autopsy data are available, and who have previously been excluded from the cohort. Future directions in which this work could be extended are also suggested.

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.

Mayak worker study: an improved biokinetic model for reconstructing doses from internally deposited plutonium.

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.

Uncertainties analysis of doses resulting from chronic inhalation of plutonium at the Mayak production association.

A method is presented to determine the uncertainties in the reported dose due to incorporated plutonium for the Mayak Worker Cohort. The methodology includes errors generated by both detection methods and modeling methods. To accomplish the task, the method includes classical statistics, Monte Carlo, perturbation, and reliability groupings. Uncertainties are reported in percent of reported dose as a function of total body burden. The cohort was initially sorted into six reliability groups, with "A" being the data set that the investigators are most confident is correct and "G" being the data set with the most ambiguous data. Categories were adjusted based on preliminary calculation of uncertainties using the sorting criteria. Specifically, the impact of transportability (the parameter used to describe the transport of plutonium from the lung to systemic organs) was underestimated, and the structure of the sort was reorganized to reflect the impact of transportability. The finalized categories are designated with Roman numerals I through V, with "I" being the most reliable. Excluding Category V (neither bioassay nor autopsy), the highest uncertainty in lung doses is for individuals from Category IV-which ranged from 90-375% for total body burdens greater than 10 Bq, along with work histories that indicated exposure to more than one transportability class. The smallest estimated uncertainties for lung doses were determined by autopsy. Category I has a 32-38% uncertainty in the lung dose for total body burdens greater than 1 Bq. First, these results provide a further definition and characterization of the cohort and, second, they provide uncertainty estimates for these plutonium exposure categories.

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.

Bone cancers in Mayak workers.

Bone cancer mortality risks were evaluated in 11,000 workers who started working at the "Mayak" Production Association in 1948-1958 and who were exposed to both internally deposited plutonium and external gamma radiation. Comparisons with Russian and U.S. general population rates indicate excess mortality, especially among females, plutonium plant workers, and workers with external doses exceeding 1 Sv. Comparisons within the Mayak worker cohort, which evaluate the role of plutonium body burden with adjustment for cumulative external dose, indicate excess mortality among workers with burdens estimated to exceed 7.4 kBq (relative risk = 7.9; 95% CI = 1.6-32) and among workers in the plutonium plant who did not have routine plutonium monitoring data based on urine measurements (relative risk = 4.1; 95% CI = 1.2-14). In addition, analyses treating the estimated plutonium body burden as a continuous variable indicate increasing risk with increasing burden (P < 0.001). Because of limitations in current plutonium dosimetry, no attempt was made to quantify bone cancer risks from plutonium in terms of organ dose, and risk from external dose could not be reliably evaluated.

Liver cancers in Mayak workers.

Liver cancer mortality risks were evaluated in 11,000 workers who started working at the "Mayak" Production Association in 1948-1958 and who were exposed to both internally deposited plutonium and external gamma radiation. Comparisons with Russian liver cancer incidence rates indicate excess risk, especially among those with detectable plutonium body burdens and among female workers in the plutonium plant. Comparisons within the Mayak worker cohort which evaluate the role of plutonium body burden with adjustment for cumulative external dose indicate excess risk among workers with burdens estimated to exceed 7.4 kBq (relative risk = 17; 95% CI = 8. 0-36) and among workers in the plutonium plant who did not have routine plutonium monitoring data based on urine measurements (relative risk = 2.8; 95% CI = 1.3-6.2). In addition, analyses treating the estimated plutonium body burden as a continuous variable indicate increasing risk with increasing burden (P < 0.001). Relative risks tended to be higher for females than for males, probably because of the lower baseline risk and the higher levels of plutonium measured in females. Because of limitations in current plutonium dosimetry, no attempt was made to quantify liver cancer risks from plutonium in terms of organ dose, and risk from external dose could not be reliably evaluated.

Characteristics of the cohort of workers at the Mayak nuclear complex.

At Branch No. 1 of the Russian State Research Center "Biophysics Institute", a registry has been created of workers at the "Mayak" Production Association, the first nuclear complex in Russia. This registry includes 18,830 persons hired at Mayak's nuclear reactors and radiochemical and plutonium production plant between 1948 and 1972. Twenty-five percent of these workers are women. As of December 31, 1994, the vital status is known for approximately 90% of the cohort members. A total of 5,118 persons have died. The cause for 97% of total deaths has been ascertained. The cohort members were exposed to both external gamma radiation and internal radiation from incorporated plutonium. The plutonium body burden has been measured in 30% of the cohort members with potential for plutonium exposure. External gamma-ray doses were in the range from tenths of milligrays to about 10 Gy, and plutonium body burdens were up to about 260 kBq. In view of the nature of the Mayak worker cohort, it has the potential to provide reasonably precise, quantitative estimates of the long-term health effects associated with chronic low-dose-rate exposure to external gamma radiation as well as internal radiation from plutonium. However, a number of issues must be addressed before credible risk estimates can be obtained from this cohort. These issues include the development of an appropriate internal comparison group and/or external rates and separating of the effects of internal and external exposures on risk estimates.

Relative role of plutonium excretion with urine and feces from human body.

The ratio of plutonium content in 35 pairs of daily fecal and urine samples from 19 former MAYAK workers several decades after the end of occupational exposure was measured in clinical conditions. No dependence of the ratio Pu(feces)/Pu(urine) on plutonium aerosol transportability, sex, and age of workers was revealed in the late times after the end of occupational exposure. It was found that at the late times after the end of occupational exposure, the ratio of feces/urine is characterized by the lognormal distribution with the median value, 0.57, and error for this index characterized geometric deviation, sigmag = 1.12 Urinary and fecal excretions were analyzed after chronic exposure to inhaled plutonium compounds of different transportability for another group of 345 workers. During 500-16,000 d after the started chronic inhalation, plutonium biokinetic model ("Doses-2000") used in Southern Ural Biophysics Institute (SUBI) and based on the ICRP Publication 66 overestimated the feces/urine ratio by an order of magnitude as compared with the observed values. It indicates a necessity for further improvement of the biokinetic model used in SUBI.

Metabolism and dosimetry of actinide elements in occupationally-exposed personnel of Russia and the United States: a summary progress report.

The United States Transuranium and Uranium Registries (USTUR) and the Dosimetry Registry of the Mayak Industrial Association (DRMIA) have been independently collecting tissues at autopsy of plutonium workers in their respective countries for nearly 30 y. The tissues are analyzed radiochemically and the analytical data are used to develop, modify, or refine biokinetic models that describe the depositions and translocations of plutonium and transplutonium elements in the human body. The purpose of this collaborative research project is to combine the unique information on humans, gathered by the two Registries, into a joint database and perform analyses of the data. A series of project tasks are directly concerned with dosimetry in Mayak workers and involve biokinetic modeling for actinide elements. Transportability coefficients derived from in-vitro solubility measurements of actinide-containing aerosols (as measured by the DRMIA) were related to specific workplaces within Mayak facilities. The transportability coefficients of inhaled aerosols significantly affected the translocation rates of plutonium from the respiratory tract to the systemic circulation. Parameters for a simplified lung model, used by Branch No. 1, Federal Research Center Institute of Biophysics (FIB-1) and the Mayak Production Association for dose assessment at long times after inhalation of plutonium-containing aerosols, were developed on the basis of joint USTUR and DRMIA data. This model has separate sets of deposition and transfer parameters for three aerosol transportability groups, allowing work histories of the workers to be considered in the dose-assessment process. FIB-1 biokinetic models were extended to include the distributions of actinide elements in systemic organs of workers, and a relationship between the health of individual workers and plutonium distribution in tissues was determined. Workers who suffered from liver diseases generally had a smaller fraction of systemic plutonium in the liver at death and a larger fraction in the skeleton than did relatively healthy workers. Also, the fraction of total systemic plutonium excreted per day was significantly greater for workers with liver diseases than for relatively healthy workers. These observations could have a considerable effect on organ dosimetry in health-impaired workers whose dose assessments were based solely on urinary excretion rates. A comparison of this model to other biokinetic models, such as those published by the International Commission for Radiological Protection, is currently underway as is the documentation of uncertainty estimates associated with the model.

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 degrees 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.

The effect of state of health on organ distribution and excretion of systemic plutonium in the Mayak workers.

The extrapulmonary distribution of plutonium in 20 organs (excluding the respiratory tract) was studied in workers who chronically inhaled plutonium at the radiochemical plants of the Mayak Production Association (Ozyorsk, Russia). The data were obtained by radiochemical analysis of soft tissue and bones samples collected at autopsy of 591 workers. The systemic plutonium distribution was determined in healthy individuals as well as in those with health impairment, specifically for those with liver diseases. Twenty-five years after the beginning of inhalation, systemic fractions in the liver and skeleton of individuals who were healthy at the time of death approximate the ratio 45%:45% proposed in the International Commission on Radiological Protection (ICRP) Publication 30. Pathological processes in the liver, accompanied by fatty dystrophy of hepatocytes, increased plutonium clearance from the liver. There was a considerable shift of the plutonium from the liver to the skeleton in individuals who died from liver disease. The average fractions of systemic plutonium in the liver and skeleton of those individuals were 14% and 78% respectively, which did not correspond to ICRP models, indicating a significant effect of disease conditions. Plutonium that was not redistributed was excreted. The urinary excretion rate of plutonium also correlated with state of health. The observed excretion as a fraction of systemic content was 1.64 x 10(-5) d(-1) for individuals in good health and 2.34 x 10(-5) d(-1) for individuals with various chronic diseases. The current models do not account for the influence of different pathological processes in the body on plutonium distribution and retention in systemic organs. This could have significant consequences for dosimetry calculations and risk estimations.