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The results of a retrospective analysis of leukocytic indices and dynamics of peripheral blood values in relation to external gamma-exposure dose among the personnel of the first atomic production facility in Russia were presented. The study was performed on the basis of the database “Leukemia in the cohort of workers of the Mayak Production Association employed in 1948-1958”. The database contains hematological, clinical and dosimetry information on the two groups of workers: the study group includes individuals with leukemia as the cause of death (n=84); control group includes personnel without hematological cancer pathology (n=300). The control group was composed by selecting 3-4 internal control cases for each leukemia case taking into account gender, age of the start of the exposure and the same accumulated absorbed dose of gamma-exposure to red bone marrow. Based on 19592 analysis of peripheral blood we had described hematopoiesis shifts along cell lines, performed correlation analysis of interrelation between hemogram values and radiation dose, analyzed particular characteristics of blast cells’ appearance in peripheral blood flow in the period prior to leukemias. Comparative analysis of various leukocytic indices was performed among Mayak PA personnel for the first time. The diverse nature of the response of bone marrow hematopoiesis was noted; more pronounced hematological shifts were indicated regarding more intensive production exposure. A number of hematopoietic features were detected among people exposed to production radiation: 1) cytopenia in relation to minimum accumulated doses of radiation exposure in both studied groups; 2) more pronounced lability of hemograms in relation to increased accumulation dose of external gamma-exposure and period of radiation exposure among individuals who had developed leukemia in future in comparison to controls; 3) correlation between peripheral blood cells and accumulated doses of external gamma-exposure was characterized by the highest values of coefficients among individuals with future leukemias; 4) myeloblasts were most often registered among all the blast cells; proerythroblasts were characterized by the shortest average period from the start of the exposure and to the moment of their appearance in the peripheral blood flow (178 days in the study group); polychromatophile erythroblasts in peripheral blood were registered only among the workers with future leukemia; 5) when comparing leukocytic indices in proportion to the categories of accumulated doses of external gamma-exposure, a pronounced variability in the ratio of blood cells was observed among exposed individuals who were subsequently diagnosed with leukemia, especially in the range of 2.0-2.5 Gy. Thus, a comprehensive analysis of hematological parameters, including the assessment of leukocytic indices, is more informative than studying a standard hemogram. Particular features of the dynamics of the cellular composition of peripheral blood can be used as indicators of pathological hematopoiesis in exposed workers prior to clinical manifestation of leukemia.

Results of development of the database “Leukemia in the cohort of workers of the Mayak Production Association employed in 1948-1958” that was developed in the Laboratory of Radiation Epidemiology of Southern Urals Biophysics Institute were presented. The database contains hematological, clinical and dosimetric information for the workers of main plants of the first production facility of Soviet atomic industry employed in the period of production development – 1948-1958. The computer database contains information for two groups of Mayak Production Association workers: main group of workers with leukemia as the main cause of death (n=84) and group of personnel without hematological cancer pathology for comparison (n=300). The comparison group was composed in such a way to allow 3-4 controls of corresponding gender, age of exposure start, accumulated dose of external gamma-exposure to red bone marrow for each leukemia case. Methods of data collection and sources of medical data were described. Characteristics of software developed for the database was presented. The database containing a total of 19593 results of blood tests reflects dynamics of hematological values in atomic facility personnel due to prolonged radiation exposure. The range of accumulated absorbed doses of external gamma-exposure to red bone marrow in the group of personnel with leukemia diagnoses was 0.001-4.96 Gy; average dose for males was 1.24 Gy and 0.61 Gy – for females. Similar range is observed in the group of personnel without leukemia outcomes. Alongside differences in accumulation rates of external radiation exposure doses is evident: in the group of workers with hematological cancer pathology the average period of radiation exposure at production facility was 14.3 years for males and 12.1 years for females; in the comparison group – 20.4 and 13.9 years, respectively. Most leukemia cases were diagnosed in the workers of radiochemical facility (54.8%). Myeloid leukemia prevailed (47.6%) in the leukemia structure; among them acute myeloid leukemia made more than a half of the cases; lymphoid leukemia was diagnosed in 14.3% cases with prevailing role of chronic lymphoid leukemia. Acute and chronic monocytic leukemia were the rarest types of malignant neoplasms of hematopoietic tissue. Possible correlation between hematological values with individual doses of external gamma- and internal alpha-exposure (incorporated Pu-239) distributed over time was stated. The database allows calculating integrated leukocytic indices reflecting response of hemopoietic system to radiation exposure, tracking changes in hemopoiesis in proportion to accumulated dose to red bone marrow, analyzing specific characteristics of rehabilitation of hematological alterations after occupational contact to ionizing radiation is terminated. Information on acute and chronic diseases available for the workers in the database allows excluding non-specific response of hemopoietic system caused by associated pathology. A revision of leukemia risk estimated in the relation to dose rate for personnel exposed to chronic radiation could be regarded as one of perspective trends in using the database.

A review of literature data regarding the heritable effects in offspring due to parents’ contact with mutagenic risk factors is presented. Studies on various factors of adverse effects on the hereditary apparatus, including chemical, infectious, physical and biological, are considered. The influence of smoking and parents’ age on the occurrence of de novo mutations is shown. Particular attention is paid to the review of publications on the role of the radiation factor in the genesis of hereditary disorders in offspring. Development stages of radiation genetics, the evolution of conception about radiation harm are described. The results of experimental, cytogenetic, molecular genetic, epidemiological studies analyzing the contribution of parental exposure to inherited pathology in progeny are presented. Special attention is paid to the “untargeted” effects of radiation and studies which prove the possibility of transgenerative transmission of genome instability are presented. The special contribution of studies on the cohort of atomic bomb victims offspring in Hiroshima and Nagasaki, which is considered as the main scientific platform for radiation risk assessment, is noted. There are articles about the offspring of persons who underwent therapeutic exposure, who had professional contact with ionizing radiation, who were exposed to radiation as a result of the Chernobyl accident, nuclear weapons tests at the Semipalatinsk test site, chronic radiation in the radioactively contaminated territory of the Techa river, areas with naturally increased radioactivity. As a result, it was noted that, despite numerous confirmations of radiation-induced effects in offspring obtained within experimental and molecular genetic studies, the results of epidemiological studies remain controversial. Possible reasons for these discrepancies are considered. An idea of views evolution regarding heritable effects in the international system of radiation safety is given. A new approach of the International Commission on Radiological Protection to heritable effects is described; the dynamics of tissue weighting factors for gonads in the assessment of effective radiation dose is shown. Methods for evaluating heritable effects are presented: the direct method and the doubling dose method. Attention is focused on the uncertainties that remain in the modern assessment of radiation genetic damage. The necessity of further study of radiation-induced heritable effects is shown. The perspective directions of studying the heritable effects are considered. The possibility of the analysis of heritable effects is described using the example of a cohort of the Mayak Production Association workers’ offspring – the country’s first nuclear industry enterprise.

The workers at the Mayak nuclear facility near Ozyorsk, Russia are a primary source of information about exposure to radiation at low-dose rates, since they were subject to protracted exposures to external gamma rays and to internal exposures from plutonium inhalation. Here we re-examine lung cancer mortality rates and assess the effects of external gamma and internal plutonium exposures using recently developed Monte Carlo dosimetry systems. Using individual lagged mean annual lung doses computed from the dose realizations, we fit excess relative risk (ERR) models to the lung cancer mortality data for the Mayak Workers Cohort using risk-modeling software. We then used the corrected-information matrix (CIM) approach to widen the confidence intervals of ERR by taking into account the uncertainty in doses represented by multiple realizations from the Monte Carlo dosimetry systems. Findings of this work revealed that there were 930 lung cancer deaths during follow-up. Plutonium lung doses (but not gamma doses) were generally higher in the new dosimetry systems than those used in the previous analysis. This led to a reduction in the risk per unit dose compared to prior estimates. The estimated ERR/Gy for external gamma-ray exposure was 0.19 (95% CI: 0.07 to 0.31) for both sexes combined, while the ERR/Gy for internal exposures based on mean plutonium doses were 3.5 (95% CI: 2.3 to 4.6) and 8.9 (95% CI: 3.4 to 14) for males and females at attained age 60. Accounting for uncertainty in dose had little effect on the confidence intervals for the ERR associated with gamma-ray exposure, but had a marked impact on confidence intervals, particularly the upper bounds, for the effect of plutonium exposure [adjusted 95% CIs: 1.5 to 8.9 for males and 2.7 to 28 for females]. In conclusion, lung cancer rates increased significantly with both external gamma-ray and internal plutonium exposures. Accounting for the effects of dose uncertainty markedly increased the width of the confidence intervals for the plutonium dose response but had little impact on the external gamma dose effect estimate. Adjusting risk estimate confidence intervals using CIM provides a solution to the important problem of dose uncertainty. This work demonstrates, for the first time, that it is possible and practical to use our recently developed CIM method to make such adjustments in a large cohort study.

Background: It is scientifically uncertain whether in utero exposure to low-dose ionising radiation increases the lifetime risk of haematological malignancies. Methods: We pooled two cohorts from the Southern Urals comprising offspring of female workers of a large nuclear facility (the Mayak Production Association) and of women living in areas along the Techa River contaminated by nuclear accidents/waste from the same facility, with detailed dosimetry. Results: The combined cohort totalled 19 536 subjects with 700 504 person-years at risk over the period of incidence follow-up, and slightly more over the period of mortality follow-up, yielding 58 incident cases and 36 deaths up to age 61 years. Risk was increased in subjects who received in utero doses of ⩾80 mGy (excess relative risk (ERR): 1.27; 95% confidence interval (CI): −0.20 to 4.71), and the risk increased consistently per 100 mGy of continuous exposure in utero (ERR: 0.77; CI: 0.02 to 2.56). No association was apparent in mortality-based analyses. Results for leukaemia and lymphoma were similar. A very weak positive association was observed between incidence and postnatal exposure. Conclusions: In summary, the results suggest a positive association between in utero exposure to ionising radiation and risk of haematological malignancies, but the small number of outcomes and inconsistent incidence and mortality findings preclude firm conclusions.

In this study, lung cancer risk from occupational plutonium exposure was analyzed in a pooled cohort of Mayak and Sellafield workers, two of the most informative cohorts in the world with detailed plutonium urine monitoring programs. The pooled cohort comprised 45,817 workers: 23,443 Sellafield workers first employed during 1947-2002 with follow-up until the end of 2005 and 22,374 Mayak workers first employed during 1948-1982 with follow-up until the end of 2008. In the pooled cohort 1,195 lung cancer deaths were observed (789 Mayak, 406 Sellafield) but only 893 lung cancer incidences (509 Mayak, 384 Sellafield, due to truncated follow-up in the incidence analysis). Analyses were performed using Poisson regression models, and were based on doses derived from individual radiation monitoring data using an updated dose assessment methodology developed in the study. There was clear evidence of a linear association between cumulative internal plutonium lung dose and risk of both lung cancer mortality and incidence in the pooled cohort. The pooled point estimates of the excess relative risk (ERR) from plutonium exposure for both lung cancer mortality and incidence were within the range of 5-8 per Gy for males at age 60. The ERR estimates in relationship to external gamma radiation were also significantly raised and in the range 0.2-0.4 per Gy of cumulative gamma dose to the lung. The point estimates of risk, for both external and plutonium exposure, were comparable between the cohorts, which suggests that the pooling of these data was valid. The results support point estimates of relative biological effectiveness (RBE) in the range of 10-25, which is in broad agreement with the value of 20 currently adopted in radiological protection as the radiation weighting factor for alpha particles, however, the uncertainty on this value (RBE = 21; 95% CI: 9-178) is large. The results provide direct evidence that the plutonium risks in each cohort are of the same order of magnitude but the uncertainty on the Sellafield cohort plutonium risk estimates is large, with observed risks consistent with no plutonium risk, and risks five times larger than those observed in the Mayak cohort.

For almost 50 y, the Life Span Study cohort of atomic bomb survivor studies has been the primary source of the quantitative estimates of cancer and non-cancer risks that form the basis of international radiation protection standards. However, the long-term follow-up and extensive individual dose reconstruction for the Russian Mayak worker cohort (MWC) and Techa River cohort (TRC) are providing quantitative information about radiation effects on cancer risks that complement the atomic bomb survivor-based risk estimates. The MWC, which includes ~26 000 men and women who began working at Mayak between 1948 and 1982, is the primary source for estimates of the effects of plutonium on cancer risks and also provides information on the effects of low-dose rate external gamma exposures. The TRC consists of ~30 000 men and women of all ages who received low-dose-rate, low-dose exposures as a consequence of Mayak's release of radioactive material into the Techa River. The TRC data are of interest because the exposures are broadly similar to those experienced by populations exposed as a consequence of nuclear accidents such as Chernobyl. In this presentation, it is described the strengths and limitations of these three cohorts, outline and compare recent solid cancer and leukemia risk estimates and discussed why information from the Mayak and Techa River studies might play a role in the development and refinement of the radiation risk estimates that form the basis for radiation protection standards.

Exposure to ionizing radiation has well-documented long-term effects on cancer rates and other health outcomes in humans. While in vitro experimental studies had demonstrated that the nature of some radiation effects depend on both total dose of the radiation and the dose rate (i.e., the pattern of dose distribution over time), the question of whether or not the carcinogenic effect of radiation exposure depends on the dose rate remains unanswered. Another issue of interest concerns whether or not concomitant exposure to external gamma rays and inhaled plutonium aerosols has any effect on the external exposure effects. The analyses of the present paper focus on the risk of solid cancers at sites other than lung, liver, and bone in Mayak workers. Recent findings are reviewed indicating that there is no evidence of plutonium dose response for these cancers in the Mayak worker cohort. Then the evidence for differences in the external dose effects among workers with and without the potential for exposure to alpha particles from inhaled plutonium is examined. It is found that there is no evidence that exposure to plutonium aerosols significantly affects the risk associated with external exposure. While the Mayak external dose risk estimate of an excess relative risk of 0.16 per Gy is somewhat lower than an appropriately normalized risk estimate from the Life Span Study of Japanese atomic bomb survivors, the uncertainties in these estimates preclude concluding that the external dose excess relative risks of this group of solid cancers differ in the two cohorts.

Workers at the Mayak nuclear facility in the Russian Federation offer the only adequate human data for evaluating cancer risks from exposure to plutonium. Risks of mortality from cancers of the lung, liver and bone, the organs receiving the largest doses from plutonium, were evaluated in a cohort of 17,740 workers initially hired 1948-1972 using, for the first time, recently improved individual organ dose estimates. Excess relative risk (ERR) models were used to evaluate risks as functions of internal (plutonium) dose, external (primarily gamma) dose, gender, attained age and smoking. By December 31, 2003, 681 lung cancer deaths, 75 liver cancer deaths and 30 bone cancer deaths had occurred. Of these 786 deaths, 239 (30%) were attributed to plutonium exposure. Significant plutonium dose-response relationships (p < 0.001) were observed for all 3 endpoints, with lung and liver cancer risks reasonably described by linear functions. At attained age 60, the ERRs per Gy for lung cancer were 7.1 for males and 15 for females; the averaged-attained age ERRs for liver cancer were 2.6 and 29 for males and females, respectively; those for bone cancer were 0.76 and 3.4. This study is the first to present and compare dose-response analyses for cancers of all 3 organs. The unique Mayak cohort with its high exposures and well characterized doses has allowed quantification of the plutonium dose-response for lung, liver and bone cancer risks based on direct human data. These results will play an important role in plutonium risk assessment.

Studies of cancer risk following in utero exposure to ionizing radiation are limited in number, particularly for adult-onset cancers, and the evidence is unclear. In the present study, the risk of solid cancer incidence following in utero radiation exposure is examined among 8466 offspring of female nuclear workers at one of the largest nuclear facilities (Mayak Production Association) in the Russian Federation. Poisson regression methods were used to estimate excess relative risks (ERRs) per Gray (Gy). Mother’s uterine gamma dose served as a surrogate for fetal gamma dose. During 277,002 person-years of follow-up (1948–2009), there were 177 first primary solid cancers excluding non-melanoma skin cancers. Estimated in utero gamma and plutonium doses exceeded zero for 41 and 23 % of offspring, respectively. Of the 177 solid cancers, 66 occurred among individuals with some in utero exposure to gamma radiation and 53 among those with estimated plutonium exposures. There was no indication of a statistically significantly increased risk of solid cancer incidence from in utero gamma exposure (linear ERR/Gy −1.0; upper 95 % confidence limit 0.5). This result was unchanged after accounting for subsequent occupational exposure. Plutonium doses were estimated but were too low to obtain meaningful risk estimates. Thus, in this cohort in utero radiation exposure was not associated with solid cancer risk. This is consistent with an earlier report of mortality in the cohort, but is based on twice as many cases and less susceptible to biases inherent in mortality analyses. Given the relatively young age of the cohort with respect to cancer, continued follow-up should be done as the number of cancer cases increases.

Radiation effects on mortality from solid cancers other than lung, liver, and bone cancer in the Mayak worker cohort: 1948–2008. The cohort of Mayak Production Association (PA) workers in Russia offers a unique opportunity to study the effects of prolonged low dose rate external gamma exposures and exposure to plutonium in a working age population. We examined radiation effects on the risk of mortality from solid cancers excluding sites of primary plutonium deposition (lung, liver, and bone surface) among 25,757 workers who were first employed in 1948–1982. During the period 1948–2008, there were 1,825 deaths from cancers other than lung, liver and bone. Using colon dose as a representative external dose, a linear dose response model described the data well. The excess relative risk per Gray for external gamma exposure was 0.16 (95% CI: 0.07 – 0.26) when unadjusted for plutonium exposure and 0.12 (95% CI 0.03 – 0.21) when adjusted for plutonium dose and monitoring status. There was no significant effect modification by sex or attained age. Plutonium exposure was not significantly associated with the group of cancers analyzed after adjusting for monitoring status. Site-specific risks were uncertainly estimated but positive for 13 of the 15 sites evaluated with a statistically significant estimate only for esophageal cancer. Comparison with estimates based on the acute exposures in atomic bomb survivors suggests that the excess relative risk per Gray for prolonged external exposure in Mayak workers may be lower than that for acute exposure but, given the uncertainties, the possibility of equal effects cannot be dismissed.

Kreisheimer, M., Koshurnikova, N. A., Nekolla, E., Khokhryakov, V. F., Romanow, S. A., Sokolnikov, M. E., Shilnikova, N. S., Okatenko, P. V. and Kellerer, A. M. 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 γ-ray exposure and internal α-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 γ rays. The baseline lung cancer mortality rate has not been taken from national statistics but has been derived from the cohort itself. For both α particles and γ rays, the results of the analysis are consistent with linear dose dependences. The e...

At present, direct data on risk from protracted or fractionated radiation exposure at low dose rates have been limited largely to studies of populations exposed to low cumulative doses with resulting low statistical power. We evaluated the cancer risks associated with protracted exposure to external whole-body gamma radiation at high cumulative doses (the average dose is 0.8 Gy and the highest doses exceed 10 Gy) in Russian nuclear workers. Cancer deaths in a cohort of about 21,500 nuclear workers who began working at the Mayak complex between 1948 and 1972 were ascertained from death certificates and autopsy reports with follow-up through December 1997. Excess relative risk models were used to estimate solid cancer and leukemia risks associated with external gamma-radiation dose with adjustment for effects of plutonium exposures. Both solid cancer and leukemia death rates increased significantly with increasing gamma-ray dose (P0.001). Under a linear dose-response model, the excess relative risk for lung, liver and skeletal cancers as a group (668 deaths) adjusted for plutonium exposure is 0.30 per gray (P0.001) and 0.08 per gray (P0.001) for all other solid cancers (1062 deaths). The solid cancer dose-response functions appear to be nonlinear, with the excess risk estimates at doses of less than 3 Gy being about twice those predicted by the linear model. Plutonium exposure was associated with increased risks both for lung, liver and skeletal cancers (the sites of primary plutonium deposition) and for other solid cancers as a group. A significant dose response, with no indication of plutonium exposure effects, was found for leukemia. Excess risks for leukemia exhibited a significant dependence on the time since the dose was received. For doses received within 3 to 5 years of death the excess relative risk per gray was estimated to be about 7 (P0.001), but this risk was only 0.45 (P = 0.02) for doses received 5 to 45 years prior to death. External gamma-ray exposures significantly increased risks of both solid cancers and leukemia in this large cohort of men and women with occupational radiation exposures. Risks at doses of less than 1 Gy may be slightly lower than those seen for doses arising from acute exposures in the atomic bomb survivors. As dose estimates for the Mayak workers are improved, it should be possible to obtain more precise estimates of solid cancer and leukemia risks from protracted external radiation exposure in this cohort.

Long-term effects of in utero exposure to ionizing radiation remain poorly quantified in humans. In this study, the risk of hematologic malignancies was investigated in offspring of female workers of the Mayak Production Association, a large Russian nuclear facility. Excess relative risks (ERR) for exposure to gamma radiation and plutonium were estimated in a cohort of 8,466 offspring who were born between January 1, 1948 and December 31, 1988 and followed until 2009. An unstable linear ERR of 1.12 (95% CI 0.11-3.44) per 100 mGy gamma exposure in utero was estimated based on 32 incident hematologic malignancies in 277,002 person-years under risk. The ERR was increased in the dose category 20-79 mGy gamma exposure in utero (1.75, 95% CI 0.04; 5.63), while the other dose categories showed decreased or unstable estimates. Leukemia showed an ERR of 1.76 (95% CI 0.01-8.33) per 100 mGy based on 13 cases. There was no consistent association with plutonium exposure. While an increased risk of hematologic malignancies after gamma exposure in utero was suggested, the small numbers prevented more definitive conclusions.

Little is known about long-term cancer risks following in utero radiation exposure. We evaluated the association between in utero radiation exposure and risk of solid cancer and leukemia mortality among 8,000 offspring, born from 1948–1988, of female workers at the Mayak Nuclear Facility in Ozyorsk, Russia. Mother’s cumulative gamma radiation uterine dose during pregnancy served as a surrogate for fetal dose. We used Poisson regression methods to estimate relative risks (RRs) and 95% confidence intervals (CIs) of solid cancer and leukemia mortality associated with in utero radiation exposure and to quantify excess relative risks (ERRs) as a function of dose. Using currently available dosimetry information, 3,226 (40%) offspring were exposed in utero (mean dose = 54.5 mGy). Based on 75 deaths from solid cancers (28 exposed) and 12 (6 exposed) deaths from leukemia, in utero exposure status was not significantly associated with solid cancer: RR = 0.94, 95% CI 0.58 to 1.49; ERR/Gy = −0.1 (95% CI < −0.1 to 4.1), or leukemia mortality; RR = 1.65, 95% CI 0.52 to 5.27; ERR/Gy = −0.8 (95% CI < −0.8 to 46.9). These initial results provide no evidence that low-dose gamma in utero radiation exposure increases solid cancer or leukemia mortality risk, but the data are not inconsistent with such an increase. As the offspring cohort is relatively young, subsequent analyses based on larger case numbers are expected to provide more precise estimates of adult cancer mortality risk following in utero exposure to ionizing radiation.

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. q 2004 by Radiation Research Society

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 (P0.001). 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.

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.

Workers at the Mayak nuclear facility in the Russian Federation offer a unique opportunity to evaluate health risks from exposure to inhaled plutonium. Risks of mortality from lung cancer, the most serious carcinogenic effect of plutonium, were evaluated in 14,621 Mayak workers who were hired in the period from 1948–1982, followed for at least 5 years, and either monitored for plutonium or never worked with plutonium. Over the follow-up period from 1953–2008, there were 486 deaths from lung cancer, 446 of them in men. In analyses that were adjusted for external radiation dose and smoking, the plutonium excess relative risk (ERR) per Gy declined with attained age and was higher for females than for males. The ERR per Gy for males at age 60 was 7.4 (95% CI: 5.0–11) while that for females was 24 (95% CI: 11–56). When analyses were restricted to plutonium doses

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.

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 (P0.001). 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.