Mayak Worker Study Project 2.4 Volume III Internal Dosimetry Dose Reconstruction Methods Used in Preparation of Doses-2005 Database

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1 Mayak Worker Study Project 2.4 Volume III Internal Dosimetry Dose Reconstruction Methods Used in Preparation of Doses-2005 Database Project 2.4: Southern Urals Biophysics Institute V. Khokhriakov V. Khokhriakov, Jr. N. Koshurnikova N. Shilnikova P. Okatenko V. Kreslov M. Bolotnikova M. Sokolnikov K. Suslova S. Romanov Mayak Production Association: Е. K. Vasilenko University of Utah: S. C. Miller Melinda Krahenbuhl Oak Ridge National Laboratory: K. F. Eckerman Project 2.2: Southern Urals Biophysics Institute N. Koshurnikova U.S. National Cancer Institute E. Gilbert March 15, 2007

2 Abstract The Doses-2005 database was prepared by Project 2.4 researchers for use in epidemiologic analyses of Mayak Production Association (MPA) workers. The database includes external dose as described in Volume I and II, and internal dose as described herein. The MPA Enterprise is the first industrial nuclear complex in Russia and its construction in the late-1940s involved many first-of-a-kind facilities, equipment, and processes that were later found to be inadequate, and this situation resulted in comparably high exposures to workers. 3

3 Contents Section Page Acronyms and Abbreviations Overview History and Background of SUBI Center of Radiation Medicine and Archives on Medical and Dosimetric Records of Mayak Production Association Workers Progression and Development of Internal Dosimetry Systems for Plutonium: FIB-1, Doses-1999, Doses-2000, Doses Doses-2005 Model for Internal Doses for Plutonium Exposures Use of biophysical measurement data Use of measurements of plutonium content at autopsy Reevaluation of early (pre-1972) radiochemical methods Determination of the ratio of feces/urine for workers at later periods after intake could be used to improve the systemic and lung clearance models for plutonium? Development of typical Worker Exposure Profiles for different work locations, events, and times Documentation of accidents and incidents Determination of influence of health status on biokinetics, deposition, and subsequent dosimetry calculations Determination of effect of smoking on plutonium biokinetics and resultant dosimetry Documentation of the use of DTPA and utilize this information to improve the dosimetry data in existing cohort Determination of physical, chemical, and biological behavior ( transportability ) of industrial aerosols characteristic of different industrial work locations Improvement and extension of internal dosimetry cohorts with new data obtained by whole-body counting methods Improvement and adaptation of Leggett systemic model (ICRP Publication 67) for Doses Creation of combined biokinetic plutonium model of systemic retention and lung clearance and development of new internal dosimetry algorithm for dose calculation: Doses References

4 Tables Table Page 3.1 Characteristics of internal plutonium dosimetry models; Doses 1999 and Doses Reliability groups 1-V Number of workers with internal dose and occupational records and with or without external dose and occupational records sorted by dose reliability categories Example of original data for a bioassay measurement Organs used for determinations of 239 Pu concentrations found in autopsy database Registered contingency radionuclide intakes in nuclear workers Parameters used in lung component of the model IDs of plutonium production sites with determined transportability coefficients General characteristic of workers for whom plutonium exposures were estimated by 241 Am gamma-radiation measurements Transfer coefficients used in the Doses 2005 model...22 Figures Figure Page 4.1 Doses-2005 model

5 Acronyms and Abbreviations DOE DTPA FIB-1 JCCRER MINATOM MPA SUBI USTUR UU WBC U.S. Department of Energy diethylenetriaminepentaacetic acid Branch 1 of the First Institute of Biophysics Joint Coordinating Committee for Radiation Effects Research Ministry of Atomic Energy Mayak Production Association Southern Urals Biophysics Institute U.S. Transuranium and Uranium Registries University of Utah whole-body counter 6

6 1.0 Overview This volume describes the history of the Southern Urals Biophysics Institute (SUBI), formerly Branch 1 of the First Institute of Biophysics (FIB-1), and the development of the archive of medical and dosimetric records from the Mayak Production Association (MPA). The task for internal dosimetry was to develop an updated dosimetry system such that organ doses from internal exposures to plutonium could be calculated, estimated, or extrapolated. The initial dosimetry system employed the FIB-1 model, which was replaced in sequence by the Doses-1999 and Doses-2000 models. The details, development, and progression of these internal plutonium dosimetry models have been well documented in the peerreviewed, public-domain literature listed at the end of this report. The Doses-2000 model has been used from 2000 to the present, but is being replaced by an updated model, Doses The new model was developed using data sets that were unique to Mayak workers and other sources such as the International Commission on Radiological Protection (ICRP). This model consists of two major parts: a lung model and a systemic model. Both parts were described in detail in recent manuscript publications. The combined model (Doses-2005) with the various transfer coefficients will be summarized in this report, but the reader is referred to the published literature for technological details. Throughout this report, the reader will be referred to supporting published literature, when available. Publications that were derived specifically from the Internal Dosimetry Team during the course of these studies are listed in the Project 2.4 Internal Dosimetry Bibliography. 7

7 2.0 History and Background of SUBI Center of Radiation Medicine and Archives on Medical and Dosimetric Records of Mayak Production Association Workers Construction on the MPA began in the summer of The first spent fuel elements were dissolved in December 1948, with the first separation of plutonium product completed by February 1949, and the finished product completed later that year. During the period from 1948 to 1955, six nuclear reactors and two radiochemical plants entered into production. Of the six reactors, five were graphite-moderated while the sixth was originally a heavy-water reactor. In the early years of MPA operation, a number of workers were exposed to significant amounts of radiation and radioactive materials, largely due to unfamiliarity with this emerging technology and a series of incidents and accidents. To address some of the health-related issues associated with these radiation exposures, a scientific/medical division was created in May This division was originally part of the MPA Central Laboratory and Medical Sanitary Department-71, and later became FIB-1 and more recently SUBI. The initial function of the Division was to accumulate primary dosimetry and medical information on MPA workers to address occupational and work-related issues that would protect worker health by decreasing harmful radiation exposures. The Division was initially led by G. D. Baysogolov and A. K. Guskova and within the first 5 yr of operation provided unique information on the health consequences of acute and chronic radiation exposures. Of particular interest were effects on the hematopoietic system and other clinical indicators of exposures. These early data were used to help control worker exposures by occupational and/or leave assignments and to also implement medical monitoring and intervention, when needed. It was the results of these early studies that led the central Soviet Ministry Research Council to establish a more formal branch at the MPA, thus FIB-1. This provided an improved infrastructure to accumulate primary medical and dosimetry monitoring information and provide medical care and support. There was considerable emphasis in the period from 1953 to the 1960s to implement monitoring for plutonium exposures. The early monitoring approaches were elementary by today s standards, but were implemented to address the significant problem of inhalation exposures by the workers. In the mid- 1950s, the need to implement biophysical examinations was apparent and some early data on plutonium uptake, retention, and metabolism in humans were obtained from autopsy materials. Some of the exposures to plutonium in the initial years of plant operations were so high that affected individuals appeared to have chronic radiation sickness. The recognition of this radiation-related illness prompted the initiation of some basic science and clinical research studies at FIB-1. These included radiobiology studies on the dosimetry, metabolism, and toxicity of alpha-emitting radionuclides in biological systems. Various animal models were developed to study these scientific issues. Inhalation of contaminated aerosols was recognized as the main route of internal contamination and, beginning in about 1957, use of the Lepestok respirator was introduced. This helped reduce occupational exposures, along with other improvements in personnel protection, such that there has been a gradual decline in exposures from 1958 to the present. The Internal Dosimetry Laboratory was created at the FIB-1 in 1967 to study plutonium metabolism with the goal of reducing worker exposures and improving worker health. The laboratory began to accumulate data on radionuclide metabolism in the workers and to develop and improve detection and measurement methods. From the initial data that were accumulated from early Mayak workers, attempts were made to 8

8 begin to estimate the longer term accumulation and retention of plutonium in the human and to estimate radiation doses to organs and tissues. Due to the now well-known concept of latency (the time from exposure to clinical manifestation), many of the first clinical symptoms of early respiratory exposures began to become apparent in the 1960s. For example, a number of cases (about 123) of plutonium pneumosclerosis were diagnosed. Additionally, cancers that were suspected of having a radiation etiology from earlier exposures began to appear. Thus, the longer term (stochastic) effects of radiation exposures (internal and external) on morbidity and mortality started to become evident. In the following decade (1970s), research into the various exposure situations, including metabolism, dosimetry, and the resulting health consequences began to intensify. During this period, very unique data obtained at autopsy and from urine bioassays were used to develop some of the early radiation guidelines for the former Soviet Union. The first Directive Guidelines (IMU-72) were issued by FIB-1 in about 1972 and were used to provide dosimetry estimates for cohorts used in some of the initial epidemiological studies conducted on these workers. These early epidemiological studies were some of the first to explore relationships between human exposures to significant internal and external radiation exposures and the incidence of oncological diseases and other pathologies. Some of the results from these early studies were published in the Soviet literature and one monograph, in particular, was published in 1971 and translated into English in 1973 in the United States and distributed through the U.S. Library of Congress. In the mid-1970s, more advanced radiochemical methods and techniques for the analysis of plutonium and americium in biological materials are introduced at the Biophysics Laboratory at FIB-1. This greatly increased the capabilities of the laboratory to detect and measure plutonium and americium in biological samples. In the early 1980s, a whole-body counter (WBC) installed at the Biophysics Laboratory greatly increased the capability to detect and measure the whole-body content of 241 Am in the individual. Individuals with higher than background levels of 241 Am were suspected of being exposed to greater amounts of plutonium. These individuals were used for bioassay measurements of plutonium. Thus, the use of the WBC became, and continues to be, a valuable worker screening tool and collaboration effort between FIB-1 and the Radiological Protection Service at the MPA. In the late 1980s, new guidelines, similar to those of the ICRP (ICRP Publication 30; ICRP 1979) for plutonium dosimetry were developed (Directive Guidelines IMU-88). These guidelines remain in use today for dosimetry control at Ministry of Atomic Energy (MINATOM) enterprises. During the 1970s and 1980s, medical and dosimetry studies were significantly expanded to consider environmental exposures. This was particularly important for areas contaminated by the tank explosion in 1957 (the Kystym Explosion ) that contaminated a large area extending from the plant to the northeast (the East Ural Radioactive Track, or EURT) and exposed about one quarter of a million people to radiation. An estimated 2 million curies of radiation were expelled into the atmosphere. Of interest to the investigators at FIB-1 was to reconstruct the cumulative dose from all sources of radiation. This was done using data from autopsies, in vivo measurements, bioassays, and information on environmental exposures and other sources of information, such as film badge dosimetric data obtained from the MPA. From the 1950s through the 1990s, the medical and dosimetry records were largely contained in paper records. In the early 1990s, computerization and creation of electronic databases of some of these records began and continue to the present. The various databases included information on autopsy data (about 1,200 cases), bioassay measurements, chelation records, and other important information on plutonium and americium exposures. These records were used and continue to be used by statisticians and epidemiologists to study the health consequences of the radiation exposures. 9

9 In the late 1980s, more direct contacts and collaborations between scientists at FIB-1 and foreign scientists were initiated. Some of the motivation for these collaborations was perhaps driven by the political expediency of dealing with the Chernobyl accident at the international level. With time, the unique dosimetric and medical records contained at the FIB-1 and MPA became recognized, and there was a growing interest to initiate formal international collaborations. On January 14, 1994, an agreement on cooperation to study the health consequences of radiation exposures at the MPA was signed between the Russian Federation and the United States. Thus, the Joint Coordinating Committee for Radiation Effects Research (JCCRER) was formally established. The U.S. Department of Energy (DOE) is the managing agency of the program for the United States, but incorporates other participating Federal agencies including the U.S. Nuclear Regulatory Commission, U.S. Department of Defense, and the U.S. Department of Health and Human Services. On the Russian side, the participating agencies were the Ministry for Civil Defense Affairs, Emergencies and Elimination of Consequences of Natural Disasters, MINATOM, and Ministry of Health. Since the inception of the JCCRER, numerous collaborative studies have been initiated between scientists from SUBI and foreign investigators. Under the JCCRER, the initial collaborative studies were with investigators from the U.S. Transuranium and Uranium Registries (USTUR) at the University of Washington and investigators from the University of Utah (UU). With USTUR, techniques for the radiochemical and spectroscopic analyses of alpha-emitting isotopes were modernized and standardized between the USTUR and SUBI. Additionally, improvements in the detection of soft-gamma radiation were made, and are useful for routine and emergency examination of personnel. With investigators from UU and later with Oak Ridge National Laboratory, a series of improvements was made in the internal dosimetry system for plutonium (the topic of this report). This included a sequential improvement of models used to calculate internal doses to organs that began with the FIB-1 model, then the Doses-1999 model, the Doses-2000 model, and now the Doses-2005 model (summarized later in this report). With the development of these models were sequential improvements in the database that contains the dosimetric records of the Mayak worker cohort (about 18,600 in the original cohort). With investigators from the USTUR and later with DOE, the Radiological Department at SUBI created an archive of biological materials and tissue samples obtained from Mayak workers. Materials in this archive are being used to support studies that include the molecular and cell biology of radiation-induced cancers and studies on the organ, tissue, and cellular localization of plutonium in human tissues determined by various autoradiographic methods. Perhaps one of the most important activities of the joint Russian-U.S. study is the creating of a large database that contains health and medical records, dosimetry and other exposure information, and occupational and work history information on the Mayak workers. Comparing the information in this data base with registries in other countries, there are some unique aspects of the database and the Mayak worker cohort. Some of these include: A large and well-documented cohort Documented exposures to plutonium in a significant population of workers Higher radiation exposures permitting a broad range of dose-effects studies Ability to distinguish external and internal exposures in much of the cohort The potential to study the effects of exposures to other radionuclides including 241Am and uranium fission products 10

10 Khokhryakov and Vasilenko (2003) published additional unique characteristics and features of the Mayak worker database and dosimetry system. 11

11 3.0 Progression and Development of Internal Dosimetry Systems for Plutonium: FIB-1, Doses-1999, Doses-2000, Doses-2005 The model used to calculate annual organ doses from plutonium exposures was called the FIB-1 model and was based on the so-called Durbin Model. In 1999, the FIB-1 model was updated and referred to as Doses-1999 and in the following year as Doses Details on the development and application of these models have been published (Khokhryakov et al. 2000a; Khokhryakov et al. 2000b; Khokhryakov et al. 2002a; Krahenbuhl et al. 2002; Khokhryakov 2004). The distinguishing features of the model are listed in Table 3.1. Both models, as well as the new Doses model have two major components: a pulmonary clearance model and a systemic model. Table 3.1. Characteristics of internal plutonium dosimetry models; Doses 1999 and Doses 2000.* Attribute Doses-1999 Doses-2000 Worker database Period of employment, work location, and trade Period of employment, work location, and trade Aerosol characteristics Particle size not addressed. Solubility characterized in physiological saline. Three transportability groups defined. Large particles assumed. Solubility characterized in physiological saline. Three transportability groups defined. Respiratory tract Simple model considering long-term Structure of respiratory model of ICRP-66 with model Systemic model dynamics Systemic burden estimated from modified Durbin excretion function. Fixed systemic distribution estimated from autopsy data. absorption based on transportability groups Systemic burden estimated from modified Durbin excretion function. Fixed systemic distribution estimated from autopsy data. Dosimetry model Absorbed dose averaged over entire organ Absorbed dose averaged over entire organ *From Table 2 in: Leggett et al The uncertainties associated with the Internal Doses 2000 Dosimetry Model were recently published (Krahenbuhl et al. 2005). The method to estimate uncertainties associated with total body doses derived from the Doses-2000 model includes errors generated by both detection and modeling methods. The approach used standard statistics, Monte Carlo, perturbation, and reliability groups. Using an approach that was previously used in the Sellafield worker studies, we sorted members of the cohort into reliability groups. This approach has several advantages including a better characterization of the entire cohort and statistical uncertainties estimated for each of these reliability groups. We identified five uncertainty categories based on how and when plutonium content was determined (e.g. autopsy, bioassay, nonmeasured) and transportability (transport to the systemic circulation) characteristics (e.g. fast, medium, and slow). The transportability (identified as S in our manuscripts) correlates with the characteristics of the various industrial aerosols to which the workers were exposed. For example, the less soluble plutonium dioxide compounds were found to have a solubility of 0.3%, the mixed compounds of 1.0%, and the more insoluble plutonium nitrate compounds of 3.0%. The solubility directly correlates with the transport of the plutonium out of the lung into the systemic circulation; more recent nomenclature (ICRP) identifies these as S (slow), M (medium), and F (fast). The five reliability categories are listed in Table 3.2. Of concern to the epidemiologists and others who use or might use these data are the relative numbers of workers who fall into these categories. Clearly, autopsy data provides the best direct measure of terminal organ plutonium content, but relatively few autopsies have been performed (about 1,200 total in the total worker cohort). Bioassays are less able to predict total body and organ plutonium content, but in many 12

12 Table 3.2. Reliability groups 1-V. Group Characteristics I Individuals with only one transportability and autopsy II Individuals with more than one transportability and autopsy III Individuals with only one transportability and bioassay IV Individuals with more than one transportability and bioassay V Individuals who were not monitored for plutonium exposure cases represent the only data available for these workers. The majority of workers who worked on locations where they could have been exposed to plutonium compounds, however, had neither a bioassay nor an autopsy. This is summarized in Table 3.3. Table 3.3. Number of workers with internal dose and occupational records and with or without external dose and occupational records sorted by dose reliability categories.* External dose and Category Internal dose records only internal dose records Total cases I II III 710 4,043 4,753 IV 92 1,636 1,728 V 3,084 11,751 14,835 *Taken from Figure 9 and Table 6 in Krahenbuhl et al

13 4.0 Doses-2005 Model for Internal Doses for Plutonium Exposures The Doses-2005 model for calculating doses to various organs from plutonium exposures is comprised of a respiratory tract model and a systemic model. The details on these two components have been recently published. Details on the respiratory (pulmonary) tract portion of Doses-2005 were recently published in Khokhryakov et al The systemic portion of the Doses-2005 model have been recently published in Leggett at al The development of the Doses-2005 model required a number of studies on various components of the model. The following summarizes some of these studies and the resultant publications that described the results. Supplementary references can be found in the publications resulting from these studies. 4.1 Use of biophysical measurement data Direct measurements of the plutonium content in the body are derived from autopsy and urine bioassay data. In these studies the internal dosimetry database was expanded and improved by the inclusion of new bioassay data obtained from current and former workers of the MPA. This task continued through the duration of the project and will continue into the future as part of the ongoing worker health program at Mayak and SUBI. The bioassay (urinalysis) data were used in the dosimetry models to calculate organ doses. This, naturally, required a number of assumptions, which are detailed in the publications that were derived from this project. The methods, procedures and data obtained from the studies conducted under this task were published by the Project 2.4 Internal Dosimetry Team (see Khokhryakov et al. 2003a; Khokhryakov et al. 2004a). An example of the bioassay data that is found in the original records and transferred into the Bioassay data base is found in the following Table 4.1. Table 4.1. Example of original data for a bioassay measurement (translated from Russian). (This example was taken from Journal 637, Page 66, ID )* Date of collection: 20/11/75 (date urine was collected from the worker for the assay) Amount of urine: 1,300 ml (24-hr collection while worker was in Health Center) Volume of sample used in assay: 200 ml Aliquot used for counting: 10 ml Background counts: 3 Counting efficiency: 13 PMT Identifier: 626 Sample counts: 40 Calculated dpm/g: 48 Final dpm/g: 48 * Other information on this individual found in the original notebook records includes name (by unique identifier), date of birth, employment dates, other sampling dates, death record (if deceased), weight at last exam, use of DTPA in the bioassay, employment and plant work history, and other information on the dates of the bioassays relative to work at the plant. 4.2 Use of measurements of plutonium content at autopsy The data obtained from the autopsy materials (e.g. organ content of alpha emitters) was considered to be the most reliable and highest quality data for calculation of organ doses. There were more than 1,200 autopsy cases from the Mayak worker cohort. The autopsy program has been completed and no further 14

14 autopsies will be performed except on a very limited basis. A special autopsy database created for this important and unique dataset is maintained in the biophysics laboratory at SUBI. The data are used to calculate organ doses using the new Doses 2005 model and were used in the models to estimate organ doses from the bioassay (urinalysis) measurements. The autopsy data have provided new insights in the effects of various diseases and lifestyle issues (e.g. smoking) on plutonium biokinetics. The use of these data for understanding the effects of smoking are presented later in this report. The effects of various late-in-life diseases, such as cancers and liver disease, are also presented later in this report. The autopsy database at SUBI complements the DOE-databases maintained in USTUR. The autopsy database contains data on the concentrations of 239 Pu in a number of organ systems. These are listed in Table 4.2. Table 4.2. Organs used for determinations of 239 Pu concentrations found in autopsy database. Liver Skeleton Skeletal muscle Spleen Kidneys Heart Thyroid gland Gonads Pancreas Gall bladder Adrenal glands Stomach Esophagus Bladder Intestine and colon Mammary gland Skin Blood Red bone marrow Lymph nodes (axillar, mesenteric, inguinal) Lung and pulmonary tree 4.3 Reevaluation of early (pre-1972) radiochemical methods Methodological and instrumentation sensitivity and error are a source of uncertainty in dosimetry calculations. In these series of studies, the early radiochemical methods were characterized and the various changes in methodology, equipment, and measurement sensitivity for the bioassay data were documented. The methodological aspects of this task were accomplished under the original Project 2.1. This included equipment and methodological improvements in the bioassay technologies and comparisons with related technologies in use in the United States. Some of the results of this work were published by Project 2.1 investigators and one paper with Project 2.4 investigators (see Khokhryakov et al. 2000c; Khokhryakov et al. 2002a; Kathren 2004). 4.4 Determination of the ratio of feces/urine for workers at later periods after intake could be used to improve the systemic and lung clearance models for plutonium? Plutonium excretion occurs via fecal and urinary routes, and is influenced by the route and pattern of plutonium exposures. For example, at early times after an inhalation exposure, the relative excretion of plutonium in the feces is greatly increased due to clearance from the lungs into the gastrointestinal tract. Later, however, the relative amount of urinary excretion will increase as plutonium enters the systemic circulation. There are, however, few data on this topic, particularly in humans. It was of interest to determine if the relative fecal/urinary ratios would be influenced by type of industrial aerosol and age and sex of the workers. It was the goal of this task to determine if these new data on human plutonium kinetics could be used to improve the dosimetric models. Indeed, the findings of this study indicated that the Doses-2000 model and the ICRP-66 model (ICRP 1994) overestimated the feces/urine ratio by about an order of magnitude. The results from these studies have been published and were utilized in the development of the Doses-2005 Internal Dosimetry Model. See Khokhryakov et al. 2003a; Khokhryakov et al. 2004b; Khokhryakov et al. undated. 15

15 4.5 Development of typical Worker Exposure Profiles for different work locations, events, and times Soon after Project 2.4 started, it became evident that much more information about the nature of the worker exposures would be needed to obtain more reliable dose estimates and to identify workers who might have been exposed, but dosimetry data was sparse or nonexistent. Then the occupational histories of the workers were obtained from the MPA and systematically entered into the database. These occupational data helped identify when and where workers might have been exposed and, if so, to what types of industrial compounds (e.g., nitrates, oxides, mixed). All of these data were then used to develop the new dosimetry models (Doses-2000 and Doses-2005). These worker exposure profiles have also been used to obtain surrogate doses when doses based on actual measurements (e.g., bioassay and autopsy) were not available. These surrogate doses can be used by the epidemiologists, and are used for specific groups of workers with the similar labor conditions given their occupation, working time, means of individual protection, air contamination, and physical-chemical properties of alpha-active aerosols. The worker exposure profiles have already been used in the initial epidemiological evaluations of both liver and bone cancers and more recently lung cancers in the Mayak worker cohort. The exposure profiles permitted the epidemiologists to segregate and identify individual workers based on location of work (e.g., reactor, plutonium plant, radiochemical plant), work period, and dates. The following publications include authors from Project 2.4 (U.S. and/or Russian): Gilbert et al. 2000; Koshurnikova et al. 2000; Shilnokova et al. 2003; Gilbert at al. 2004; and Kreisheimer et al Documentation of accidents and incidents The purpose of these studies was to document the occurrence, dates, and nature of accidents and incidents that might have resulted in acute exposures. This information is important to understand when exposures occurred and to distinguish acute vs. chronic exposures for dosimetry calculations. A database was developed that contains available information on incidents and accidental exposures to radionuclides among MPA workers. These have been obtained from records in the SUBI archives and continue to be updated as new information is obtained. Table 4.3 summarizes the information in the accidents and incidents database. Currently, the database contains information on accidental intakes of radionuclides for 653 workers. Of these, 367 workers were from cohorts of epidemiological projects on stochastic risk estimation (Project 2.2) and deterministic effects (former Project 2.3; now supported by the U.S. National Institute of Health). In total, the database contains 833 incident cases for the period from 1949 (beginning of plant operations) to March Table 4.3. Registered contingency radionuclide intakes in nuclear workers. Nuclear workers Stab wounds, cuts, scratches Skin surface contamination Acute inhalation intakes Chemica l burns Other Total Cohorts I-V* 271 (1)** 74 (0) 87 (3) 29 (0) 40 (0) 501 (4) Other 116 (2) 75 (0) 89 (7) 23 (0) 29 (0) 332 (10) Total 387 (3) 149(0) 176 (10) 52 (0) 69 (0) 833 (14) * Cohorts I-V include workers of the plutonium production and radiochemical plants employed during ** Number of female workers 4.7 Determination of influence of health status on biokinetics, deposition, and subsequent dosimetry calculations The purpose of these studies was to determine the influence of health status on the distribution of plutonium and perhaps other actinides among organs. If differences were observed, this would influence how organ doses were calculated for the individual. The studies found that certain diseases, particularly 16

16 those that occur late in life, will influence the redistribution of plutonium among the organs. These data resulted in a reevaluation and reconsideration of historical data often obtained from individuals with various late-in-life diseases. From these data, new corrections in the dosimetry calculations were made. It is important to note that the presence of disease factors that would influence the assays of plutonium content (e.g., autopsy and bioassay) can now be taken into consideration in the new Doses-2005 dosimetry system. We should also note that these findings illuminated some deficiencies in dosimetry assumptions and calculations derived from other (non-russian) populations. The results from the following studies have been published or are in press: Suslova et al. 2000; Suslova et al. 2002; Suslova et al. 2003; Suslova et al. in press; Suslova et al. submitted. 4.8 Determination of effect of smoking on plutonium biokinetics and resultant dosimetry Smoking history can influence the plutonium lung clearance model given the modifying effect(s) of smoking and other modifiers on the retention of various nuclide compounds in the respiratory tract. Additionally, smoking is the primary confounder in the interpretation of the epidemiological data, particularly considering the prevalence of smoking among Mayak workers. Information on an individual s smoking history is found in the clinical records and has now been entered into a database in the biophysics laboratory at SUBI. These smoking history data have and are being used in the epidemiological analyses of cancer risk, as indicated in the following publications from investigators who are using this database: Tokarskaya et al. 2002; Kreisheimer et al. 2003; and Gilbert et al The influence of smoking on plutonium biokinetics has been studied and the modifying factors involved with smoking or nonsmoking can now be used in the Doses-2005 Internal Dosimetry system. Thus, the influence of smoking on plutonium biokinetics can be taken into account when individual organ doses are calculated. These modifying factors were obtained from analyses of several hundred autopsy cases in which smoking history was confirmed. We found that smoking increased the retention of plutonium in the lungs, particularly with less soluble plutonium compounds. There were no significant differences observed in lung retention in the smokers vs. the nonsmokers exposed to the more soluble industrial compounds. A similar relationship was found in pulmonary lymph nodes. Much of the data derived from these studies have been published or are in press; see Khokhryakov et al. 2005; Suslova et al. submitted; and Kudryavtseva and Sokolova submitted. The parameters used in the lung component of the model are listed in the Table 4.4. S = solubility of the aerosols and the less soluble plutonium (0.3%) represents dioxides and metallic compounds; moderate soluble plutonium (3.0%) represents nitrates; and the intermediate solubility forms of plutonium (1.0%) represent mixtures of moderately soluble and insoluble compounds. Table 4.4. Parameters used in lung component of the model (after Khokhryakov et al. 2005). Smokers Nonsmokers S, % f r f 1 N f b ss, d -1 N f b ss, d Assumes an AMAD of 5 µm. 4.9 Documentation of the use of DTPA and utilize this information to improve the dosimetry data in existing cohort. DTPA was frequently used to temporarily increase the urinary output of plutonium to improve the sensitivity of the bioassay measurements. DTPA was also used, in a very few cases, to reduce the body burden of plutonium. In these studies, the use of DTPA for bioassay measurements was documented and 17

17 reviewed. This was important because a large number of the bioassays were from individuals who were taking DTPA for short periods prior to the bioassay. These data are then used to correct, adjust, and standardize the bioassay results. The records of 1,179 workers were obtained. Some of these workers were chelated more than once, resulting in 1,237 analyzed cases. The majority (about 80%) of these workers were males and most (about 75%) were exposed to plutonium prior to Most of the chelation-enhanced bioassay measurements were made from 1961 to The typical protocol was that Ca-DTPA was injected intravenously at a dose of 0.25 g/d for 3 d. Urine was collected over this 3-d period. Typically, this was done after d of vacation away from the production plant. This was done to minimize the effects of more acute exposures. The results indicate that this procedure would enhance plutonium excretion by a factor of about 62.3 during the injection period. After concurrent administration of Ca-DTPA, the enhancement factor decreased exponentially with a halftime of 3.7 d. This project became a Ph.D. dissertation topic for one of the younger scientists at SUBI; some of the results have been presented in Khokhryakov et al. 2003, and two articles by Schadilov et al. submitted for publication (included in the references list) Determination of physical, chemical, and biological behavior ( transportability ) of industrial aerosols characteristic of different industrial work locations These studies were designed to determine the solubility characteristics that would influence transport (transportability) or translocation from the lung to other tissues of the industrial aerosols that workers encountered at the Mayak complex. These data were used to derive the revised lung component of the Doses-2005 model; the results were published in the following manuscripts: Khokhryakov et al. 2000; Khokhryakov et al. 2002a; Khokhryakov et al. 2002b; Khokhryakov et al Table 4.5 summarize the sites, work period, technological processes, and the associated solubility of the industrial compounds. These data were used to develop the Doses 2005 model Improvement and extension of internal dosimetry cohorts with new data obtained by whole-body counting methods The Rocky Flats Plant WBC was installed at the Biophysics Laboratory at SUBI and became operational in These studies determined if 241 Am data obtained from the WBC could be used to screen for plutonium exposures. This was important because most of the workers were not routinely screened for plutonium exposures. In addition, the data from the WBC will provide completely new data on 241 Am in the human, but these americium data were not part of Project 2.4. The overall approach was to estimate the whole body plutonium content by measuring 241 Am by whole body counting. Measuring 241 Am by WBC is much more economical than measuring plutonium in bioassays and then having to estimate the total body content from the models. To date, 6,798 whole-body measurements have been made on 4,328 Mayak workers. Of these, 2,137 belong to the Project 2.2 cohort. At present, 256 workers from the Project 2.2 cohort have synchronous and reliable results from both biophysical assays and WBC measurements. From this group, algorithms have been developed to permit the estimation of plutonium content based on their exposure scenarios (e.g., the types of industrial compounds to which they were exposed). Some of these data have been derived from the autopsy database discussed earlier. The workers for whom plutonium exposures were estimated by 241 Am measurements are summarized in Table

18 Table 4.5. IDs of plutonium production sites with determined transportability coefficients. Site ID of workplace Work period Technological process Substrate S, % Chemicalmetallurgical Refining Nitrate solution, 1.0 Oxide, chloride Oxalate precipitation Nitrate solution, 1.0 oxalate Filtration Oxalate 1.0 Metallurgical Calcination, chlorination reducting fusion Chloride Oxide present Fuel element production Mixed aerosols 1.0 Waste treatment Dissolution, precipitation, filtration Nitrate solution Oxalate precipitation Oxalate 1.0 Chemical Sorption on VP-AP resin Nitrate solution Extraction Nitrate solution, 3.0 extract Plutonium Part blank Pu metal 0.3 production Mechanical cutting Pu metal Defectoscopy Mixed aerosols Capsulation Pu metal present Foundry-pressing Pu metal 0.3 Table 4.6. General characteristic of workers for whom plutonium exposures were estimated by 241 Am gamma-radiation measurements. Solubility Characteristics S = 0.3% S = 1.0% S = 3.0% Number of workers Working at time of examination Year of initial contact, (at average ± years) 1967 ± ± ± 9 Contact duration (average ± years) 33 ± 9 31 ± ± 14 To date, the Pu Am body burden was calculated by the Doses-2000 model and according to the WBC measurement results - total 241 Am body burden. It should be noted that the bioassay measurements of the urine do not distinguish alpha particles derived from plutonium or americium using current techniques at SUBI. Further work on 241 Am exposures in Mayak workers might be proposed in the future. Several papers (Khokhryakov et al. 2003c; Khokhryakov and Efimov 2004) describe the initial experience with the use of the whole body counter to measure 241 Am and to monitor the Mayak workers Improvement and adaptation of Leggett systemic model (ICRP Publication 67) for Doses-2005 The systemic portion of the Doses-2005 uses a revision of the ICRP Publication 67 model. Data for these studies were obtained mostly from autopsy cases. Parameters of plutonium metabolism in the skeleton, liver, and blood were revised. A manuscript that describes in detail the development and application of this systemic portion of the Doses 2005 model was recently published (Leggett et al. 2005). The overview of the entire Doses 2005 model is presented later. 19

19 4.13 Creation of combined biokinetic plutonium model of systemic retention and lung clearance and development of new internal dosimetry algorithm for dose calculation: Doses The Doses-2005 model combines the lung clearance model with the new systemic component. Both of these individual components of the Doses-2005 model have recently been published; see Khokhryakov et al and Leggett et al The final model is presented in Fig. 4.1 and the derivations and conditions placed on the components of the model are discussed in detail in the published references. 20

20 İ Pu LN ET ET seq ET 2 LN ET ET seq ET 2 BB seq BB 2 BB 1 BB seq BB 2 BB 1 LN TH bb seq bb 2 bb 1 LN TH bb seq bb 2 bb 1 Lung fast dissolution AI 1 AI 2 AI 3 Lung slow dissolution AI 1 AI 2 AI 3 LN ET ET seq ET 2 BB seq BB 2 BB 1 LN TH bb seq bb 2 bb 1 Lung bound material AI 1 AI 2 AI 3 Other soft tissue Slow turnover (ST2) Intermediate turnover (ST1) Rapid turnover (ST0) Blood 0 GI tract Stomach Liver Small Intestine Skeleton Cortical volume Trabecular volume Cortical surface Trabecular surface Cortical marrow Trabecular marrow Blood 2 Liver 0 Liver 1 Liver 2 Upper large intestine Lower large intestine Feces Urine Urinary bladder contents Kidneys Other kidney Renal tubules Blood 1 Gonads Fig Doses-2005 model. 21

21 The individual transfer coefficients currently used in the model are listed in Table 4.7. The source of the information, data, or publication used to derive the specific transfer functions are also listed. Table 4.7. Transfer coefficients used in the Doses 2005 model. Symbol Definition -s Input +s Units Source ID L3 Worker identification number -- ##### Data S Transportability coefficient , 1, Data s m Smoking coefficient -- 0, Data year Yearly markers Year Data GNK Year started working Year Data GKK Year finished working Year Data GP Year of analysis or death Year Data t i Time indexing Day Data V 0 Maximum intake rhythm Day -1 Constant g Intake exponent index (S=0.3) Year -1 Project 2.4 Intake exponent index (S=1.0) Year -1 Project 2.4 Intake exponent index (S=3.0) Year -1 Project 2.4 U m Urine bioassay for Pu 100% assay 120% dpm Krah 2005 MDA Minimum detectable activity of Pu 70% assay 150% dpm Krah 2005 M U Urine bioassay performed? -- 0, Data Q aut Pu body content via autopsy 5% assay 5% nci Krah 2005 M Q Autopsy performed? -- 0, Data m ave Average worker mass kg Data K m Shaping factor Calculated 0 1 calculated -- Calculated V I Shaped intake rhythm Calculated calculated Day -1 Calculated -box Bypass autopsy for urine K m value -- 0, Data Symbol Definition -s Model +s Units Source f r Fraction dissolved rapidly (S=0.3) Monte Carlo Monte Carlo -- Khok 2005 Fraction dissolved rapidly (S=1.0) Monte Carlo 0.01 Monte Carlo -- Khok 2005 Fraction dissolved rapidly (S=3.0) Monte Carlo 0.03 Monte Carlo -- Khok 2005 f b Fraction to bound state (S=0.3, sm=0) Monte Carlo Monte Carlo -- Khok 2005 Fraction to bound state (S=0.3, sm=1) Monte Carlo Monte Carlo -- Khok 2005 Fraction to bound state (S=1.0, sm=0) Monte Carlo Monte Carlo -- Khok 2005 Fraction to bound state (S=1.0, sm=1) Monte Carlo Monte Carlo -- Khok 2005 Fraction to bound state (S=3.0, sm=0) Monte Carlo Monte Carlo -- Khok 2005 Fraction to bound state (S=3.0, sm=1) Monte Carlo Monte Carlo -- Khok 2005 s s Slow dissolution rate (S=0.3, sm=0) Monte Carlo 3.61E-04 Monte Carlo Day -1 Khok 2005 Slow dissolution rate (S=0.3, sm=1) Monte Carlo 3.22E-04 Monte Carlo Day -1 Khok 2005 Slow dissolution rate (S=1.0, sm=0) Monte Carlo 4.75E-04 Monte Carlo Day -1 Khok 2005 Slow dissolution rate (S=1.0, sm=1) Monte Carlo 1.17E-03 Monte Carlo Day -1 Khok 2005 Slow dissolution rate (S=3.0, sm=0) Monte Carlo 1.77E-03 Monte Carlo Day -1 Khok 2005 Slow dissolution rate (S=3.0, sm=1) Monte Carlo 7.11E-03 Monte Carlo Day -1 Khok 2005 s r Rapid dissolution rate Monte Carlo 100 Monte Carlo Day -1 ICRP 66 f d1 Fraction deposited in AI 1 (s m =0) Monte Carlo 0.3 Monte Carlo -- ICRP 66 Fraction deposited in AI 1 (s m =1) Monte Carlo 0.3*0.3 Monte Carlo -- ICRP 66 f d2 Fraction deposited in AI f d1 -f d ICRP 66 f d3 Fraction deposited in AI 3 Monte Carlo 0.1 Monte Carlo -- ICRP 66 f d4 Fraction deposited in bb f d5 -f d ICRP 66 f d5 Fraction deposited in bb 2 Monte Carlo Monte Carlo -- ICRP 66 f d6 Fraction deposited in bb seq Monte Carlo Monte Carlo -- ICRP 66 f d7 Fraction deposited in BB f d8 -f d ICRP 66 f d8 Fraction deposited in BB 2 Monte Carlo Monte Carlo -- ICRP 66 f d9 Fraction deposited in BB seq Monte Carlo Monte Carlo -- ICRP 66 f d10 Fraction deposited in ET f d ICRP 66 f d11 Fraction deposited in ET seq Monte Carlo Monte Carlo -- ICRP 66 c r1 Mech. clearance from AI 1 to bb 1 Monte Carlo 0.02 Monte Carlo Day -1 ICRP 66 22

22 Table 4.7 (Continued). Transfer coefficients used in the Doses 2005 model. Symbol Definition -s Model +s Units Source c r2 Mech. clearance from AI 2 to bb 1 (s m =0) Monte Carlo Monte Carlo Day -1 ICRP 66 Mech. clearance from AI 2 to bb 1 (s m =1) Monte Carlo 0.001*0.7 Monte Carlo Day -1 ICRP 66 c r3 Mech. clearance from AI 3 to bb 1 (s m =0) Monte Carlo Monte Carlo Day -1 ICRP 66 Mech. clearance from AI 3 to bb 1 (s m =1) Monte Carlo *0.7 Monte Carlo Day -1 ICRP 66 c r4 Mech. clearance from AI 3 to LN TH Monte Carlo Monte Carlo Day -1 ICRP 66 c r5 Mech. clearance from bb 1 to BB 1 Monte Carlo 2 Monte Carlo Day -1 ICRP 66 c r6 Mech. clearance from bb 2 to BB 1 Monte Carlo 0.03 Monte Carlo Day -1 ICRP 66 c r7 Mech. clearance from bb seq to LN TH Monte Carlo 0.01 Monte Carlo Day -1 ICRP 66 c r8 Mech. clearance from BB 1 to ET 2 Monte Carlo 10 Monte Carlo Day -1 ICRP 66 (s m =0) Mech. clearance from BB 1 to ET 2 Monte Carlo 10*0.5 Monte Carlo Day -1 ICRP 66 (s m =1) c r9 Mech. clearance from BB 2 to ET 2 Monte Carlo 0.03 Monte Carlo Day -1 ICRP 66 c r10 Mech. clearance from BB seq to LN TH Monte Carlo 0.01 Monte Carlo Day -1 ICRP 66 c r11 Mech. clearance from ET 2 to GIT Monte Carlo 100 Monte Carlo Day -1 ICRP 66 c r12 Mech. clearance from ET seq to LN ET Monte Carlo Monte Carlo Day -1 ICRP 66 f dr1 Regional deposition fraction, AI Monte Carlo Monte Carlo -- ICRP 66 f dr2 Regional deposition fraction, bb Monte Carlo Monte Carlo -- ICRP 66 f dr3 Regional deposition fraction, BB Monte Carlo Monte Carlo -- ICRP 66 f dr4 Regional deposition fraction, ET 2 Monte Carlo Monte Carlo -- ICRP 66 f 1 Fraction to body from GIT (S=0.3) Monte Carlo 1.00E-05 Monte Carlo -- ICRP 30 Fraction to body from GIT (S=1.0) Monte Carlo 3.00E-05 Monte Carlo -- ICRP 30 Fraction to body from GIT (S=3.0) Monte Carlo 1.00E-04 Monte Carlo -- ICRP 30 l 1 Transfer stomach to small intestine Monte Carlo 24 Monte Carlo Day -1 ICRP 30 l 2 Transfer small to upper large intestine Monte Carlo 6 Monte Carlo Day -1 ICRP 30 l 3 Transfer upper to lower large intestine Monte Carlo 1.8 Monte Carlo Day -1 ICRP 30 l 4 Transfer lower large intestine to feces Monte Carlo 1 Monte Carlo Day -1 ICRP 30 l 5 Transfer small intestine to blood -- l 2 *f1/(1-f1) -- Day -1 ICRP 30 l 6 Transfer blood 1 to upper large intestine Monte Carlo E-02 Monte Carlo Day -1 l 7 Transfer 30% blood to soft tissue 0 Monte Carlo E+02 Monte Carlo Day -1 Legg 2005 l 8 Transfer 70% blood to blood 1 Monte Carlo E+02 Monte Carlo Day -1 Legg 2005 l 9 Transfer blood 1 to liver 0 Monte Carlo E-01 Monte Carlo Day -1 l 10 Transfer blood 1 to cortical surface Monte Carlo E-02 Monte Carlo Day -1 l 11 Transfer blood 1 to cortical volume Monte Carlo E-03 Monte Carlo Day -1 l 12 Transfer blood 1 to travecular surface Monte Carlo E-01 Monte Carlo Day -1 l 13 Transfer blood 1 to travecular volume Monte Carlo E-02 Monte Carlo Day -1 l 14 Transfer blood 1 to urinary bladder Monte Carlo E-02 Monte Carlo Day -1 l 15 Transfer blood 1 to kidney 1 (renal) Monte Carlo E-03 Monte Carlo Day -1 l 16 Transfer blood 1 to kidney 2 (other) Monte Carlo E-04 Monte Carlo Day -1 l 17 Transfer blood 1 to testes Monte Carlo E-04 Monte Carlo Day Transfer blood 1 to ovaries NA NA NA Day -1 Legg 2005 l 18 Transfer blood 1 to soft tissue 1 Monte Carlo E-02 Monte Carlo Day -1 l 19 Transfer blood 1 to soft tissue 2 Monte Carlo E-02 Monte Carlo Day -1 l 20 Transfer soft tissue 0 to blood 1 Monte Carlo E-02 Monte Carlo Day -1 Legg 2005 l 21 Transfer blood 2 to urinary bladder Monte Carlo E+00 Monte Carlo Day -1 l 22 Transfer blood 2 to blood 1 Monte Carlo E+01 Monte Carlo Day -1 l 23 Transfer blood 2 to soft tissue 0 Monte Carlo E+01 Monte Carlo Day -1 l 24 Transfer kidney 1 to urinary bladder Monte Carlo E-02 Monte Carlo Day -1 Legg 2005 l 25 Transfer kidney 2 to blood 2 Monte Carlo E-04 Monte Carlo Day -1 Legg 2005 l 26 Transfer soft tissue 1 to blood 2 Monte Carlo E-03 Monte Carlo Day -1 Legg 2005 l 27 Transfer soft tissue 2 to blood 2 Monte Carlo E-04 Monte Carlo Day -1 Legg 2005 l 28 Transfer liver 0 to small intestine Monte Carlo E-04 Monte Carlo Day -1 Legg 2005 l 29 Transfer liver 0 to liver 1 Monte Carlo E-02 Monte Carlo Day -1 Legg