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V F Khokhryakov

Publications and source records attributed to V F Khokhryakov.

At least 19 recordsLinked to original sources
PubMed2006

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.

Administration, Inhalation↗
PubMed2006

Influence of alpha and gamma radiations and non-radiation risk factors on the incidence of malignant liver tumors among Mayak PA workers.

This Mayak worker-based study focuses on evaluating possible associations between malignant liver cancers and chronic alpha irradiation, chronic gamma irradiation, and non-radiation risk factors (alcohol consumption, smoking, viral hepatitis, chemical exposure, and chronic digestive diseases). This is the first multivariate study related to liver cancer among Mayak workers. The study was performed using the nested, case-control approach and includes 44 cases of malignant liver tumors diagnosed from 1972 to 1999, and 111 matched controls. Adjusted odds ratio (OR(ad)) was evaluated relative to a group of workers with alpha radiation doses to liver (D(alpha)) < 2.0 Gy. Dose estimates of D(alpha) > 2.0 Gy (corresponding (239)Pu body burden estimates >20.4 kBq) were significantly associated (p < 0.003) with the occurrence of hemangiosarcomas (HAS) but only marginal significance (0.05 < p < 0.1) was found for hepatocellular cancers (HCC). The ORad for HAS was 41.7 [95% confidence interval (CI): 4.6, 333] for a group with D(alpha) in the range >2.0-5.0 Gy and was 62.5 (7.4, 500) for a group with D(alpha) > 5.0-16.9 Gy. The attributable risk (AR) was calculated as 82%. For HCC, O(Rad) was estimated as 8.4 (0.8, 85.3; p < 0.07) for a group with D(alpha) in the range >2.0-9.3 Gy. For the indicated group, the AR was 14%. An association with high external gamma-ray doses (D(gamma)) to the total body was revealed for both HCC and for combined liver cancers when dose was treated as a continuous variable. However, we find no evidence that chronic low doses of gamma rays are associated with liver cancer occurrence. Cholangiocarcinoma (CHC) was not associated with either alpha- or gamma-ray exposure. As expected, an association between alcohol abuse and HCC was inferred [O(Rad) = 3.3 (1.2, 9); AR = 41%] but not for CHC or HAS.

Alpha Particles↗
PubMed2005

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.

Absorption↗
PubMed2005

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.

Administration, Inhalation↗
PubMed2005

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.

Bone and Bones↗
PubMed2004

Chromosomal aberrations in lymphocytes of peripheral blood among Mayak facility workers who inhaled insoluble forms of 239PU.

A cytogenetic study was performed on 79 plutonium (Pu) workers chronically exposed to alpha radiation from inhaled, low-transportable (insoluble) compounds of airborne 239Pu and to external gamma rays. Body burden estimates for 239Pu ranged from 0 to 15.5 kBq. Chromosomal aberrations (CAs) (stable and unstable) among peripheral blood lymphocytes and cumulative alpha radiation doses were evaluated approximately 25 y after first contact with 239Pu. For the cytogenetic analyses, a standard two-day peripheral blood lymphocyte culture technique was applied. While alpha radiation doses continually increase up to the time of cytogenetic measurements, significant gamma ray exposures essentially ceased long before the time of measurement, so that alpha and gamma doses were not correlated. For the exposed workers, the mean 239Pu body burden (estimate), evaluated at the time of the cytogenetic measurement, was 1.23 +/- 0.26 kBq and the corresponding mean absorbed external gamma ray dose (estimate) to the total body was 0.076 +/- 0.009 Gy. Single and multivariate regression analyses were performed on the CA data. Stable, unstable and total aberrations increased as the 239Pu body burden increased over the range 0-4.5 kBq. However, above this range little additional increase was observed. CAs were weakly correlated with time since the first intake of 239Pu. No relationship between chromatid aberrations and 239Pu incorporation was found. Unstable (but not stable) aberrations were correlated with gamma radiation dose. No significant relationship of CA and smoking was found.

Adult↗
PubMed2004

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.

Administration, Inhalation↗
PubMed2004

Lung cancer in Mayak workers.

The cohort of nuclear workers at the Mayak Production Association, located in the Russian Federation, is a unique resource for providing information on the health effects of exposure to plutonium as well as the effects of protracted external dose. Lung cancer mortality risks were evaluated in 21,790 Mayak workers, a much larger group than included in previous evaluations of lung cancer risks in this cohort. These analyses, which included 655 lung cancer deaths occurring in the period 1955-2000, were the first to evaluate both excess relative risk (ERR) and excess absolute risk (EAR) models and to give detailed attention to the modifying effects of gender, attained age and age at hire. Lung cancer risks were found to be significantly related to both internal dose to the lung from plutonium and external dose, and risks were described adequately by linear functions. For internal dose, the ERR per gray for females was about four times higher than that for males, whereas the EAR for females was less than half that for males; the ERR showed a strong decline with attained age, whereas the EAR increased with attained age until about age 65 and then decreased. Parallel analyses of lung cancer mortality risks in Mayak workers and Japanese A-bomb survivors were also conducted. Efforts currently under way to improve both internal and external dose estimates, and to develop data on smoking, should result in more accurate risk estimates in the future.

Adolescent↗
PubMed2003

Lung cancer mortality among nuclear workers of the Mayak facilities in the former Soviet Union. An updated analysis considering smoking as the main confounding factor.

A new analysis of lung cancer mortality in a cohort of male Mayak workers who started their employment in the plutonium and reprocessing plants between 1948 and 1958 has been carried out in terms of a relative risk model. The follow-up has been extended until 1999, moreover a new dosimetry system (DOSES2000) has been established. Particular emphasis has been given to a discrimination of the effects of external gamma-exposure and internal alpha-exposure due to incorporated plutonium. This study has also utilized and incorporated the information from a cohort of Mayak reactor workers, who were exposed only externally to gamma-rays. The influence of smoking as the main confounding factor for lung cancer has been studied. The baseline lung cancer mortality rate was not taken from national statistics but was derived from the cohort itself. The estimated excess relative risk for the plutonium alpha-rays was 0.23/Sv (95%CI: 0.16-0.31). The resulting risk coefficient for external gamma-ray exposure was very low with a statistically insignificant estimate of 0.058/Sv (95%CI: -0.072-0.20). The inferred relative risk for smokers was 16.5 (95%CI: 12.6-20.5).

Cohort Studies↗
PubMed2003

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.

Body Burden↗
PubMed2003

Successful DTPA therapy in the case of 239Pu penetration via injured skin exposed to nitric acid.

This paper presents results of the radiological study and DTPA therapy for a worker exposed to a plutonium nitrate solution. Plutonium levels were measured in excreta, blood, plasma and wound for several weeks. Plutonium renal clearance ranged from 110-190 ml min(-1) to 3-4 ml min(-1) at different stages of chelation therapy. Plutonium absorption into blood from the injured skin amounted to 4.3%. As a result of intensive therapy, 96% of absorbed plutonium was successfully excreted.

Administration, Topical↗
PubMed2002

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.

Administration, Inhalation↗
PubMed2002

Interaction of radiation and smoking in lung cancer induction among workers at the Mayak nuclear enterprise.

For radiation-related cancer risk evaluation, it is important to assess not only influences of individual risk factors but also their interactive effects (e.g., additive, multiplicative, etc.). Multivariate analysis methods adapted for interactive effects allow such assessments. We have used a multivariate analysis approach to investigate the pair-wise interactions of the previously identified three main etiological factors for lung cancer induction in Russian workers of the Mayak Production Association (PA) nuclear enterprise. These three factors are as follows: (1) body burden of inhaled plutonium-239 (239Pu), an influence on absorbed alpha-radiation dose; (2) cumulative, absorbed external gamma-radiation dose to the lung; and (3) level of cigarette smoking as indicated by a smoking index (SI). The SI represents the cigarettes smoked per day times years smoking. The Mayak PA workers were exposed by inhalation to both soluble and insoluble forms of 239Pu. Based on a cohort of 4,390 persons (77% male), we conducted a nested, case-control study of lung cancer induction using 486 matched cases and controls. Each case was matched to two controls. Matching was based on five factors: sex, year of birth, year work began, profession, and workplace. Three levels of smoking were considered: low (SI = 1 to 499), used as a reference level; middle (SI = 500 to 900); and high (SI = 901 to 2,000). For lung cancer induction, a supra-multiplicative effect was demonstrated for high external gamma-ray doses (> 2.0 Gy) plus high 239Pu intakes (body burden >2.3 kBq). This observation is consistent with the hypothesis of curvilinear dose-response relationships for lung cancer induction by high- and low-LET radiations. The interaction between radiation (external gamma rays or 239Pu body burden) and cigarette smoke was found to depend on the smoking level. For the middle level of smoking in combination with gamma radiation (> 2.0 Gy) or 239Pu body burden (> 2.3 kBq), results were consistent with additive effects. However, for the high level of smoking in combination with gamma radiation (> 2.0 Gy) or 239Pu body burden (> 2.3 kBq), results were consistent with the occurrence of multiplicative effects. These results indicate that low-dose risk estimates for radiation-induced lung cancer derived without adjusting for the influence of cigarette smoking could be greatly overestimated. Further, such systematic error may considerably distort the shape of the risk vs. dose curve and could possibly obscure the presence of a dose threshold for radiation-induced lung cancer.

Aged↗
PubMed2000

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.

Aerosols↗
PubMed2000

Lung cancer mortality among male nuclear workers of the Mayak facilities in the former Soviet Union.

An analysis of lung cancer mortality in a cohort of 1,669 Mayak workers who started their employment in the plutonium and reprocessing plants between 1948 and 1958 has been carried out in terms of a relative risk model. Particular emphasis has been given to a discrimination of the effects of external gamma-ray exposure and internal alpha-particle exposure due to incorporated plutonium. This study has also used the information from a cohort of 2,172 Mayak reactor workers who were exposed only to external gamma rays. The baseline lung cancer mortality rate has not been taken from national statistics but has been derived from the cohort itself. For both alpha particles and gamma rays, the results of the analysis are consistent with linear dose dependences. The estimated excess relative risk per unit organ dose equivalent in the lung due to the plutonium alpha particles at age 60 equals, according to the present study, 0.6/Sv, with a radiation weighting factor of 20 for alpha particles. The 95% confidence range is 0.39/Sv to 1.0/Sv. For the gamma-ray component, the present analysis suggests an excess relative risk for lung cancer mortality at age 60 of 0.20/Sv, with, however, a large 95% confidence range of-0.04/Sv to 0.69/Sv.

Alpha Particles↗
PubMed2000

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.

Adult↗