Cohort profile: four early uranium processing facilities in the US and Canada.

PURPOSE: Pooling of individual-level data for workers involved in uranium refining and processing (excluding enrichment) may provide valuable insights into risks from occupational uranium and external ionizing radiation exposures. METHODS: Data were pooled for workers from four uranium processing facilities (Fernald, Mallinckrodt and Middlesex from the U.S.; and Port Hope, Canada). Employment began as early as the 1930s and follow-up was as late as 2017. Workers were exposed to high concentrations of uranium, radium, and their decay products, as well as gamma radiation and ambient radon decay products. Exposure and outcome data were harmonized using similar definitions and dose reconstruction methods. Standardized mortality ratios (SMR) were estimated. RESULTS: In total, 560 deaths from lung cancer, 503 non-malignant respiratory diseases, 67 renal diseases, 1,596 ischemic heart diseases, and 101 dementia and Alzheimer's disease (AD) were detected in the pooled cohort of over 12,400 workers (∼1,300 females). Mean cumulative doses were 45 millisievert for whole-body external ionizing radiation exposure and 172 milligray for lung dose from radon decay products. Only SMR for dementia and AD among males was statistically significant (SMR=1.29; 95% confidence interval: 1.04, 1.54). CONCLUSIONS: This is the largest study to date to examine long-term health risks of uranium processing workers.

Ischaemic heart and cerebrovascular disease mortality in uranium enrichment workers.

OBJECTIVE: Linear and non-linear dose-response relationships between radiation absorbed dose to the lung from internally deposited uranium and external sources and circulatory system disease (CSD) mortality were examined in a cohort of 23 731 male and 5552 female US uranium enrichment workers. METHODS: Rate ratios (RRs) for categories of lung dose and linear excess relative rates (ERRs) per unit lung dose were estimated to evaluate the associations between lung absorbed dose and death from ischaemic heart disease (IHD) and cerebrovascular disease. RESULTS: There was a suggestion of modestly increased IHD risk in workers with internal uranium lung dose above 1 milligray (mGy) (RR=1.4, 95% CI 0.76 to 2.3) and a statistically significantly increased IHD risk with external dose exceeding 150 mGy (RR=1.3, 95% CI 1.1 to 1.6) compared with the lowest exposed groups. ERRs per milligray were positive for IHD and uranium internal dose and for both outcomes per gray external dose, although the CIs generally included the null. CONCLUSIONS: Non-linear dose-response models using restricted cubic splines revealed sublinear responses at lower internal doses, suggesting that linear models that are common in radioepidemiological cancer studies may poorly describe the association between uranium internal dose and CSD mortality.

Dose-response relationships between internally-deposited uranium and select health outcomes in gaseous diffusion plant workers, 1948-2011.

OBJECTIVE: To examine dose-response relationships between internal uranium exposures and select outcomes among a cohort of uranium enrichment workers. METHODS: Cox regression was conducted to examine associations between selected health outcomes and cumulative internal uranium with consideration for external ionizing radiation, work-related medical X-rays and contaminant radionuclides technetium (99 Tc) and plutonium (239 Pu) as potential confounders. RESULTS: Elevated and monotonically increasing mortality risks were observed for kidney cancer, chronic renal diseases, and multiple myeloma, and the association with internal uranium absorbed organ dose was statistically significant for multiple myeloma. Adjustment for potential confounders had minimal impact on the risk estimates. CONCLUSION: Kidney cancer, chronic renal disease, and multiple myeloma mortality risks were elevated with increasing internal uranium absorbed organ dose. The findings add to evidence of an association between internal exposure to uranium and cancer. Future investigation includes a study of cancer incidence in this cohort.

Exposure to Recycled Uranium Contaminants in Gaseous Diffusion Plants.

As part of an ongoing study of health effects in a pooled cohort of gaseous diffusion plant workers, organ dose from internal exposure to uranium was evaluated. Due to the introduction of recycled uranium into the plants, there was also potential for exposure to radiologically significant levels of 99Tc, 237Np and 238,239Pu. In the evaluation of dose response, these radionuclide exposures could confound the effect of internal uranium. Using urine bioassay data for study subjects reported in facility records, intakes and absorbed dose to bone surface, red bone marrow and kidneys were estimated as these organs were associated with a priori outcomes of interest. Additionally, 99Tc intakes and doses were calculated using a new systemic model for technetium and compared to intakes and doses calculated using the current model recommended by the International Commission on Radiological Protection. Organ absorbed doses for the transuranics were significant compared to uranium doses; however, 99Tc doses calculated using the new systemic model were significant as well. Use of the new model resulted in an increase in 99Tc-related absorbed organ dose of a factor of 8 (red bone marrow) to 30 (bone surface).

Method for analyzing left-censored bioassay data in large cohort studies.

In retrospective epidemiological studies of large cohorts of workers exposed to radioactive materials, it is often necessary to analyze large numbers of bioassay data sets containing censored values, or values recorded as less than a detection limit. Censored bioassay data create problems for all bioassay analysis methods, including analytical techniques based on least-squares regression to estimate intakes. A method is presented here that uses a simple empirically-derived equation for imputing replacement values for urine uranium concentration results reported as zero or less than a detection limit, that produces minimal bias in intakes estimated using least-square regression methods with the assumption of lognormally distributed measurement errors.

Mortality in a combined cohort of uranium enrichment workers.

OBJECTIVE: To examine the patterns of cause-specific mortality and relationship between internal exposure to uranium and specific causes in a pooled cohort of 29,303 workers employed at three former uranium enrichment facilities in the United States with follow-up through 2011. METHODS: Cause-specific standardized mortality ratios (SMRs) for the full cohort were calculated with the U.S. population as referent. Internal comparison of the dose-response relation between selected outcomes and estimated organ doses was evaluated using regression models. RESULTS: External comparison with the U.S. population showed significantly lower SMRs in most diseases in the pooled cohort. Internal comparison showed positive associations of absorbed organ doses with multiple myeloma, and to a lesser degree with kidney cancer. CONCLUSION: In general, these gaseous diffusion plant workers had significantly lower SMRs than the U.S. POPULATION: The internal comparison however, showed associations between internal organ doses and diseases associated with uranium exposure in previous studies. Am. J. Ind. Med. 60:96-108, 2017. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Internal exposure to uranium in a pooled cohort of gaseous diffusion plant workers.

Intakes and absorbed organ doses were estimated for 29 303 workers employed at three former US gaseous diffusion plants as part of a study of cause-specific mortality and cancer incidence in uranium enrichment workers. Uranium urinalysis data (>600 000 urine samples) were available for 58 % of the pooled cohort. Facility records provided uranium gravimetric and radioactivity concentration data and allowed estimation of enrichment levels of uranium to which workers may have been exposed. Urine data were generally recorded with facility department numbers, which were also available in study subjects' work histories. Bioassay data were imputed for study subjects with no recorded sample results (33 % of pooled cohort) by assigning department average urine uranium concentration. Gravimetric data were converted to 24-h uranium activity excretion using department average specific activities. Intakes and organ doses were calculated assuming chronic exposure by inhalation to a 5-µm activity median aerodynamic diameter aerosol of soluble uranium. Median intakes varied between 0.31 and 0.74 Bq d(-1) for the three facilities. Median organ doses for the three facilities varied between 0.019 and 0.051, 0.68 and 1.8, 0.078 and 0.22, 0.28 and 0.74, and 0.094 and 0.25 mGy for lung, bone surface, red bone marrow, kidneys, and liver, respectively. Estimated intakes and organ doses for study subjects with imputed bioassay data were similar in magnitude.

Mortality and ionising radiation exposures among workers employed at the Fernald Feed Materials Production Center (1951-1985).

OBJECTIVES: To examine mortality patterns and dose-response relations between ionising radiation and mortality outcomes of a priori interest in 6409 uranium workers employed for at least 30 days (1951-1985), and followed through 2004. METHODS: Cohort mortality was evaluated through standardised mortality ratios (SMR). Linear excess relative risk (ERR) regression models examined associations between cause-specific mortality and exposures to internal ionising radiation from uranium deposition, external gamma and x-ray radiation, and radon decay products, while adjusting for non-radiologic covariates. RESULTS: Person-years at risk totalled 236 568 (mean follow-up 37 years), and 43% of the cohort had died. All-cause mortality was below expectation only in salaried workers. Cancer mortality was significantly elevated in hourly males, primarily from excess lung cancer (SMR=1.25, 95% CI 1.09 to 1.42). Cancer mortality in salaried males was near expectation, but lymphohaematopoietic malignancies were significantly elevated (SMR=1.52, 95% CI 1.06 to 2.12). A positive dose-response relation was observed for intestinal cancer, with a significant elevation in the highest internal organ dose category and a significant dose-response with organ dose from internal uranium deposition (ERR=1.5 per 100 µGy, 95% CI 0.12 to 4.1). CONCLUSIONS: A healthy worker effect was observed only in salaried workers. Hourly workers had excess cancer mortality compared with the US population, although there was little evidence of a dose-response trend for any cancer evaluated except intestinal cancer. The association between non-malignant respiratory disease and radiation dose observed in previous studies was not apparent, possibly due to improved exposure assessment, different outcome groupings, and extended follow-up.

Estimation of internal exposure to uranium with uncertainty from urinalysis data using the InDEP computer code.

The National Institute for Occupational Safety and Health (NIOSH) is currently studying mortality in a cohort of 6409 workers at a former uranium processing facility. As part of this study, over 220 000 urine samples were used to reconstruct organ doses due to internal exposure to uranium. Most of the available computational programs designed for analysis of bioassay data handle a single case at a time, and thus require a significant outlay of time and resources for the exposure assessment of a large cohort. NIOSH is currently supporting the development of a computer program, InDEP (Internal Dose Evaluation Program), to facilitate internal radiation exposure assessment as part of epidemiological studies of both uranium- and plutonium-exposed cohorts. A novel feature of InDEP is its batch processing capability which allows for the evaluation of multiple study subjects simultaneously. InDEP analyses bioassay data and derives intakes and organ doses with uncertainty estimates using least-squares regression techniques or using the Bayes' Theorem as applied to internal dosimetry (Bayesian method). This paper describes the application of the current version of InDEP to formulate assumptions about the characteristics of exposure at the study facility that were used in a detailed retrospective intake and organ dose assessment of the cohort.

Exposure assessment for a cohort of workers at a former uranium processing facility.

Exposure was assessed for a cohort of 6409 workers at a former uranium processing facility as part of a mortality study. Workers at the facility had potential for exposure to a wide variety of radiological and chemical agents including uranium, thorium, radon, external ionizing radiation, acid mists, asbestos, and various solvents. Organ dose from internal exposure to uranium was assessed, along with dose from external ionizing radiation and exposure to radon. Qualitative assessment of exposure to thorium, acid mists, asbestos, coal dust, welding fumes, and other chemicals was also performed. Mean cumulative organ dose from internal uranium exposure ranged from 1.1 mGy (lung) to 6.7 µGy (pancreas). Mean cumulative external ionizing radiation dose was 13.4 mGy. Mean cumulative radon exposure was 26 working level months (WLMs). The chemical agents to which the largest numbers of study subjects were exposed were acid mists, machining fluids, and a tributyl phosphate/kerosene mixture used in the refining process.

Bremsstrahlung doses from natural uranium ingots.

In the past, some privately owned commercial facilities in the United States were involved in producing or processing radioactive materials used in the production of atomic weapons. Seven different geometrical objects, representative of the configurations of natural uranium metal potentially encountered by workers at these facilities, are modelled to determine gamma ray and bremsstrahlung dose rates. The dose rates are calculated using the MCNP5 code and also by using the MICROSHIELD point-kernel code. Both gamma ray and bremsstrahlung dose rates are calculated and combined to obtain a total dose rate. The two methods were found to be in good agreement despite differences in modelling assumptions and method differences. Computed total dose rates on the surface of these objects ranged from approximately 51-84 microSv h(-1) and 17-95 microSv h(-1) using the MCNP5 and the MICROSHIELD modeling, respectively. The partitioning of the computed dose rates between gamma rays and bremsstrahlung were the same order of magnitude for each object.