Sergey A. Romanov

Cancer Mortality Risk among Workers at the Mayak Nuclear Complex

Abstract Shilnikova, N. S., Preston, D. L., Ron, E., Gilbert, E. S., Vassilenko, E. K., Romanov, S. A., Kuznetsova, I. S., Sokolnikov, M. E., Okatenko, P. V., Kreslov, V. V. and Koshurnikova, N. A. Cancer Mortality Risk among Workers at the Mayak Nuclear Complex. Radiat. Res. 159, 787–798 (2003). 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 γ 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 γ-radiation dose with adjustment for effects of plutonium exposures. Both solid cancer and leukemia death rates increased significantly with increasing γ-ray dose (P < 0.001). 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 (P < 0.001) and 0.08 per gray (P < 0.001) 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 (P < 0.001), but this risk was only 0.45 (P = 0.02) for doses received 5 to 45 years prior to death. External γ-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.

Liver Cancers in Mayak Workers

Abstract Gilbert, E. S., Koshurnikova, N. A., Sokolnikov, M., Khokhryakov, V. F., Miller, S., Preston, D. L., Romanov, S. A., Shilnikova, N. S., Suslova, K. G. and Vostrotin, V. V. Liver Cancers in Mayak Workers. Liver cancer mortality risks were evaluated in 11,000 workers who started working at the “Mayak” Production Association in 1948–1958 and who were exposed to both internally deposited plutonium and external γ radiation. Comparisons with Russian liver cancer incidence rates indicate excess risk, especially among those with detectable plutonium body burdens and among female workers in the plutonium plant. Comparisons within the Mayak worker cohort which evaluate the role of plutonium body burden with adjustment for cumulative external dose indicate excess risk among workers with burdens estimated to exceed 7.4 kBq (relative risk = 17; 95% CI = 8.0–36) and among workers in the plutonium plant who did not have routine plutonium monitoring data based on urine measurements (relative risk = 2.8; 95% CI = 1.3–6.2). In addition, analyses treating the estimated plutonium body burden as a continuous variable indicate increasing risk with increasing burden (P < 0.001). Relative risks tended to be higher for females than for males, probably because of the lower baseline risk and the higher levels of plutonium measured in females. Because of limitations in current plutonium dosimetry, no attempt was made to quantify liver cancer risks from plutonium in terms of organ dose, and risk from external dose could not be reliably evaluated.

Bone Cancers in Mayak Workers

Abstract Koshurnikova, N. A., Gilbert, E. S., Sokolnikov, M., Khokhryakov, V. F., Miller, S., Preston, D. L., Romanov, S. A., Shilnikova, N. S., Suslova, K. G. and Vostrotin, V. V. 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 γ 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.

Lung Cancer in Mayak Workers

Abstract Gilbert, E. S., Koshurnikova, N. A., Sokolnikov, M. E., Shilnikova, N. S., Preston, D. L., Ron, E., Okatenko, P. V., Khokhryakov, V. F., Vasilenko, E. K., Miller, S., Eckerman, K. and Romanov, S. A. Lung Cancer in Mayak Workers. Radiat. Res. 162, 505–516 (2004). 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.

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

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

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

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

Mortality among personnel who worked at the Mayak complex in the first years of its operation.

Epidemiological studies revealed increased cancer mortality among persons who began working at the Mayak complex during the period 1948-1958. Estimation of cancer risk was carried out for the sites of cancer that showed increased mortality and dependence on dose of external gamma- or internal alpha-irradiation.

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

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

Estimation of the temporal distribution and dose dependency of lung cancers among workers of nuclear fuel reprocessing plants.

Lung cancer mortality among 4,279 workers at the Mayak nuclear complex who were exposed to chronic irradiation both externally and internally from incorporation of plutonium was analyzed in terms of a linear relative risk model. It is estimated that excess lung cancer risk is about 1.9 Sv(-1), with an average latent period of 24 y.

The basic directions and results of activities of branch no. 1 of the state research center of the Russian Federation "Biophysics Institute" (FIB-1).

During the 1950s, in the early years at the Mayak Production Association (MAYAK) in the Southern Urals, there was a rapid expansion of plutonium output. This was carried out when nuclear technology was still being developed and knowledge of the effects of radiation exposure on humans was not well understood. As result of the discharge of liquid waste into the Techa River, there was large scale overexposure to both the workers at the facility and the population of riverside localities on the Techa River. There were also other environmental discharges, due to an accident and problems of waste storage, which contributed to exposure of other populations around MAYAK. Although all information on the MAYAK operation and its consequences for both workers and population was kept secret, studies on nuclear technology improvement, the handling of radioactive waste, of medical sequence of radiation exposure, radiation safety improvement, and prevention and treatment of radiation injuries were initiated virtually from the onset the of nuclear weapons production program.