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Epidemiological study of workers and analysis of health effects of uranium compounds according to their solubility

​Sergey Zhivin has defended his thesis on 30th November 2015 at University Paris-Sud, in Villejuif (France).

Document type > *Mémoire/HDR/Thesis

Keywords >

Research Unit > IRSN/DRPH/SRBE/LEPID

Authors > ZHIVIN Sergey

Publication Date > 30/11/2015

Summary

External γ-radiation exposure has been shown to be associated with mortality risk due to leukemia, solid cancer, and, possibly, circulatory diseases (CSD). By contrast, little information is available on health risks following the internal contamination, especially the inhalation of uranium compounds with respect to their physicochemical properties (PCP), such as solubility, isotopic composition and others.

The aim of this PhD thesis was to estimate mortality risk of cancer and non-cancer diseases in French nuclear fuel cycle workers and comprises three objectives: (1) evaluation of the impact of uranium on mortality through a critical literature review, (2) analysis of cancer and non-cancer mortality in a cohort of uranium enrichment workers, (3) analysis of the relationship between CSD mortality and internal uranium dose in AREVA NC Pierrelatte workers.

Existing epidemiological data on uranium PCP and associated health outcomes are scarce. Studies of nuclear fuel cycle workers by sub-groups within the specific stage of the cycle (e.g., uranium enrichment and fuel fabrication) are considered the most promising to shed light on the possible associations, given that such sub-groups present the advantage of a more homogenous uranium exposure.

To study the mortality risk associated with exposure to rapidly soluble uranium compounds, we set up a cohort of 4,688 uranium enrichment workers with follow-up between 1968 and 2008. Individual annual exposure to uranium, external γ-radiation, and other non-radiological hazards (trichloroethylene, heat, and noise) were reconstructed from job-exposure matrixes (JEM) and dosimetry records. Over the follow-up period, 131,161 person-years at risk were accrued and 21% of the subjects had die. Analysis of Standardized Mortality Ratios (SMR) showed a strong healthy worker effect (SMR all deaths 0.69, 95% confidence intervals (CI) 0.65 to 0.74; n=1,010). Exposures to uranium and external γ-radiation were not significantly associated with any cause of mortality in log-linear and linear excess relative risk models. A monotonic decreasing trend was observed for lung and lymphohematopoietic cancers across uranium exposure categories.

Previous analysis of a cohort of AREVA NC Pierrelatte uranium processing workers suggested that exposure to uranium may increase CSD mortality. A nested case-control study was set up to analyze the dose-response relationship and adjust for major CSD risk factors (smoking, blood pressure, body mass index, total cholesterol, and glycemia) collected from medical files. The study included 102 CSD cases and 416 controls matched on attained age, gender, birth cohort, and socio-professional status. Absorbed dose was calculated taking into account the solubility of uranium compounds extracted from the JEM. CSD risk was analyzed by conditional logistic regression. A positive but imprecise association was observed (excess odds ratio per mGy 0.2, 95% CI 0.004 to 0.5). None of the considered CSD risk factor confounded this association.

Compared to previous studies, our work provided important methodological improvements: consideration of specific uranium PCP, calculation of uranium organ doses, and adjustment on potential confounding factors (non-radiological exposures and CSD risk factors). The absence of association between exposure to rapidly soluble uranium compounds and mortality in the cohort of uranium enrichment workers may be indicative of the effective elimination of uranium from the human body. Analysis within the nested case-control study confirmed an association between uranium exposure and CSD mortality, not confounded by CSD risk factors. Our results should be confirmed in further studies. Future work should focus on uncertainties associated with internal uranium dose estimation, on nature of association with CSD mortality, and on temporal relationships between radiation and CSD risk factors.

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