Mortality among Tennessee Eastman Corporation (TEC) uranium processing workers, 1943-2019.

BACKGROUND: There are few occupational studies of women exposed to ionizing radiation. During World War II, the Tennessee Eastman Corporation (TEC) operated an electromagnetic field separation facility of 1152 calutrons to obtain enriched uranium (235U) used for the Hiroshima atomic bomb. Thousands of women were involved in these operations. MATERIALS AND METHODS: A new study was conducted of 13,951 women and 12,699 men employed at TEC between 1943 and 1947 for at least 90 days. Comprehensive dose reconstruction techniques were used to estimate lung doses from the inhalation of uranium dust based on airborne measurements. Vital status through 2018/2019 was obtained from the National Death Index, Social Security Death Index, Tennessee death records and online public record databases. Analyses included standardized mortality ratios (SMRs) and Cox proportional hazards models. RESULTS: Most workers were hourly (77.7%), white (95.6%), born before 1920 (58.3%), worked in dusty environments (57.0%), and had died (94.9%). Vital status was confirmed for 97.4% of the workers. Women were younger than men when first employed: mean ages 25.0 years and 33.0 years, respectively. The estimated mean absorbed dose to the lung was 32.7 mGy (max 1048 mGy) for women and 18.9 mGy (max 501 mGy) for men. The mean dose to thoracic lymph nodes (TLNs) was 127 mGy. Statistically significant SMRs were observed for lung cancer (SMR 1.25; 95% CI 1.19, 1.31; n = 1654), nonmalignant respiratory diseases (NMRDs) (1.23; 95% CI 1.19, 1.28; n = 2585), and cerebrovascular disease (CeVD) (1.13; 95% CI 1.08, 1.18; n = 1945). For lung cancer, the excess relative rate (ERR) at 100 mGy (95% CI) was 0.01 (-0.10, 0.12; n = 652) among women, and -0.15 (-0.38, 0.07; n = 1002) among men based on a preferred model for men with lung doses <300 mGy. NMRD and non-Hodgkin lymphoma were not associated with estimated absorbed dose to the lung or TLN. CONCLUSIONS: There was little evidence that radiation increased the risk of lung cancer, suggesting that inhalation of uranium dust and the associated high-LET alpha particle exposure to lung tissue experienced over a few years is less effective in causing lung cancer than other types of exposures. There was no statistically significant difference in the lung cancer risk estimates between men and women. The elevation of certain causes of death such as CeVD is unexplained and will require additional scrutiny of workplace or lifestyle factors given that radiation is an unlikely contributor since only the lung and lymph nodes received appreciable dose.

Mortality among workers at the Los Alamos National Laboratory, 1943-2017.

BACKGROUND: During World War II (WWII), the Manhattan Engineering District established a secret laboratory in the mountains of northern New Mexico. The mission was to design, construct and test the first atomic weapon, nicknamed 'The Gadget' that was detonated at the TRINITY site in Alamogordo, NM. After WWII, nuclear weapons research continued, and the laboratory became the Los Alamos National Laboratory (LANL). MATERIALS AND METHODS: The mortality experience of 26,328 workers first employed between 1943 and 1980 at LANL was determined through 2017. Included were 6157 contract workers employed by the ZIA Company. Organ dose estimates for each worker considered all sources of exposure, notably photons, neutrons, tritium, 238Pu and 239Pu. Vital status determination included searches within the National Death Index, Social Security Administration and New Mexico State Mortality Files. Standardized Mortality Ratios (SMR) and Cox regression models were used in the analyses. RESULTS: Most workers (55%) were hired before 1960, 38% had a college degree, 25% were female, 81% white, 13% Hispanic and 60% had died. Vital status was complete, with only 0.1% lost to follow-up. The mean dose to the lung for the 17,053 workers monitored for radiation was 28.6 weighted-mGy (maximum 16.8 weighted-Gy) assuming a Dose Weighting Factor of 20 for alpha particle dose to lung. The Excess Relative Risk (ERR) at 100 weighted-mGy was 0.01 (95%CI -0.02, 0.03; n = 839) for lung cancer. The ERR at 100 mGy was -0.43 (95%CI -1.11, 0.24; n = 160) for leukemia other than chronic lymphocytic leukemia (CLL), -0.06 (95%CI -0.16, 0.04; n = 3043) for ischemic heart disease (IHD), and 0.29 (95%CI 0.02, 0.55; n = 106) for esophageal cancer. Among the 6499 workers with measurable intakes of plutonium, an increase in bone cancer (SMR 2.44; 95%CI 0.98, 5.03; n = 7) was related to dose. The SMR for berylliosis was significantly high, based on 4 deaths. SMRs for Hispanic workers were significantly high for cancers of the stomach and liver, cirrhosis of the liver, nonmalignant kidney disease and diabetes, but the excesses were not related to radiation dose. CONCLUSIONS: There was little evidence that radiation increased the risk of lung cancer or leukemia. Esophageal cancer was associated with radiation, and plutonium intakes were linked to an increase of bone cancer. IHD was not associated with radiation dose. More precise evaluations will await the pooled analysis of workers with similar exposures such as at Rocky Flats, Savannah River and Hanford.

Historical perspective on the department of energy mortality studies: focus on the collection and storage of individual worker data.

PURPOSE: To present how the Department of Energy's (DOE) Comprehensive Epidemiologic Data Resource (CEDR) is integrated into the Million Person Study of Low Dose Health Effects (MPS). The history of DOE's worker health surveillance and its epidemiology program are described. METHODS AND MATERIALS: A standard protocol is used to extract data from CEDR for use in the MPS. The data files are pulled from CEDR to form the basis for the cohort analyzed in the MPS. The previous study data are reviewed to formulate the protocol for the MPS study cohort. The activities needed to update the data to construct the new analytic files are carried out in parallel. The primary efforts relate to updating the vital status, retrieving cause of death information and calculating annual radiation doses for the specific organs of interest. Working data files containing the updated data are produced for construction of analytic data files used in the biostatistical analysis. At study completion the working and analytic data files are placed into CEDR for use by other researchers. RESULTS: The use of CEDR to study the scientific and maintenance workers at the Los Alamos National Laboratory which is currently underway is used to demonstrate the process. CONCLUSIONS: There is a pressing need to answer the question of the health risk of exposure to chronic low-level exposure to ionizing radiation. Using CEDR as the starting point to identify new cohorts to include in the MPS is a cost-effective and a time efficient way to expedite answering this question.

Updated mortality analysis of the Mallinckrodt uranium processing workers, 1942-2012.

PURPOSE: Mallinckrodt Chemical Works (MCW) was the earliest uranium processing facility in the United States, and in 1942 produced the uranium oxide used for the first sustained and controlled nuclear fission chain-reaction at the University of Chicago. A second follow-up through 2012 was conducted of 2514 White male workers employed 1942-1966 at the MCW for dose-response analyses for selected causes of death. MATERIALS AND METHODS: Organ/tissue-specific dose reconstruction included both external (12,686 MCW film badge records, 210 other facility film badge records, and 31,297 occupational chest x-rays) and internal sources of uranium and radium (39,451 urine bioassays, 2341 breath radon measurements, and 6846 ambient radon measurements). Dust measurements from pitchblende facilitated quantitative risk estimates for non-radiogenic effects on the lung and kidney. Vital status was determined from multiple sources including the National Death Index and the Social Security Administration. Cox regression models were used for dose response analyses. RESULTS: Vital status was determined for 99% of the workers, of whom 75% had died. The mean lung dose from all sources of external and internal radiation combined was 69.9 mGy (maximum 885 mGy; percent workers >100 mGy, 10%) and there was no evidence for a dose response for lung cancer (Hazard Ratio (HR) of 0.95 (95% CI = 0.81-1.12) at 100 mGy). A significant association with radiation was found for kidney cancer (HR of 1.73 (95% CI = 1.04-2.79) at 100 mGy) and suggested for nonmalignant kidney diseases (HR of 1.30 (95% CI = 0.96-1.76) at 100 mGy). A non-radiation etiology could not be discounted, however, because of the possible renal toxicities of uranium, a heavy metal, and silica, a component of pitchblende dust. Non-significant HRs at 100 mGy for other sites of a priori interest were 0.36 (0.06-2.03) for leukemia other than CLL, 0.68 (0.17-2.77) for liver cancer, and 1.23 (0.79-1.90) for non-Hodgkin lymphoma. The HR at 100 mGy was 1.09 (0.99-1.20) for ischemic heart disease. An association was seen between dust and combined malignant and non-malignant lung disease, HR at 10 mgm-3year-1 of 1.01 (1.00-1.02). CONCLUSIONS: A positive radiation dose response was observed for malignant and non-malignant kidney disease, and a negative dose response for malignant and non-malignant lung disease. Cumulative measures of dust were significantly associated with malignant and non-malignant lung disease and suggested for malignant and non-malignant kidney disease. Small numbers preclude definitive interpretations which will await the combination with similar studies of early uranium processing workers.

Dosimetry is Key to Good Epidemiology: Workers at Mallinckrodt Chemical Works had Seven Different Source Exposures.

Mallinckrodt Chemical Works was the earliest uranium processing facility in the Manhattan Project, beginning in 1942. Even then, concern existed about possible health effects resulting from exposure to radiation and pitchblende dust. This concern was well founded as the facility processed Belgian Congo pitchblende ore that was up to 60% pure uranium with high U content and up to 100 mg of radium per ton. Workers were exposed to external gamma radiation plus internal radiation from inhalation and ingestion of pitchblende dust (uranium, radium, and silica). Multiple sources of exposure were available for organ dose reconstruction to a degree unique for an epidemiologic study. Personal film badge measures available from 1945 captured external exposures. Additional external exposure included 15,518 occupational medical x-rays and 210 radiation exposure records from other facilities outside of Mallinckrodt employment. Organ dose calculations considered organ-specific coefficients that account for photon energy and job-specific orientation of workers to the radiation source during processing. Intakes of uranium and radium were based on 39,451 uranium urine bioassays and 2,341 breath radon measurements, and International Commission on Radiological Protection (ICRP) Publication 68 biokinetic models were used to estimate organ-specific radiation absorbed dose. Estimates of exposure to airborne radon and its short-lived progeny were based on radon measurements in work areas where radium-containing materials were handled or stored, together with estimated exposure times in these areas based on job titles. Dose estimates for radon and its short-lived progeny were based on models and methods recently recommended in ICRP Publication 137. This comprehensive dosimetric approach follows methods outlined by the National Council on Radiation Protection Scientific Committee 6-9 for the Million Worker Study. Annual doses were calculated for six organs: lung, brain, heart, kidney, colon and red bone marrow. Evaluation and adjustment for individual cumulative measures of pitchblende dust inhalation were made for lung and kidney diseases.

The Past Informs the Future: An Overview of the Million Worker Study and the Mallinckrodt Chemical Works Cohort.

The purpose of this paper is to present an overview of ongoing work on the Million Worker Study (MWS), highlighting some of the key methods and progress so far as exemplified by the study of workers at the Mallinckrodt Chemical Works (MCW). The MWS began nearly 25 y ago and continues in a stepwise fashion, evaluating one study cohort at a time. It includes workers from U.S. Department of Energy (DOE) Manhattan Project facilities, U.S. Nuclear Regulatory Commission (NRC) regulated nuclear power plants, industrial radiographers, U.S. Department of Defense (DoD) nuclear weapons test participants, and physicians and technologists working with medical radiation. The purpose is to fill the major gap in radiation protection and science: What is the risk when exposure is received gradually over time rather than briefly as for the atomic bomb survivors? Studies published or planned in 2018 include leukemia (and dosimetry) among atomic veterans, leukemia among nuclear power plant workers, mortality among workers at the MCW, and a comprehensive National Council on Radiation Protection and Measurements (NCRP) Report on dosimetry for the MWS. MCW has a singular place in history: the 40 tons (T) of uranium oxide produced at MCW were used by Enrico Fermi on 2 December 1942 to produce the first manmade sustained and controlled nuclear reaction, and the atomic age was born. Seventy-six years later, the authors followed the over 2,500 MCW workers for mortality and reconstructed dose from six sources of exposure: external gamma rays from the radioactive elements in pitchblende; medical x rays from occupationally required chest examinations; intakes of pitchblende (uranium, radium, and silica) measured by urine samples; radon breath analyses and dust surveys overseen by Robley Evans and Merril Eisenbud; occupational exposures received before and after employment at MCW; and cumulative radon concentrations and lung dose from the decay of radium in the work environment. The unique exposure reconstructions allow for multiple evaluations, including estimates of silica dust. The study results are relevant today. For example, NASA is interested that radium, deposited in the brain, releases high-LET alpha particles - the only human analogue, though limited, for high energy, high-Z particles (galactic cosmic rays) traveling through space that might affect astronauts on Mars missions. Don't discount the past; it's the prologue to the future!

Illness absences among beryllium sensitized workers.

OBJECTIVES: This study examined absence rates among US Department of Energy workers who had beryllium sensitization (BeS) or were diagnosed with chronic beryllium disease (CBD) compared with those of other workers. METHODS: We used the lymphocyte proliferation test to determine beryllium sensitivity. In addition, we applied multivariable logistic regression to compare absences from 2002 to 2011 between workers with BeS or CBD to those without, and survival analysis to compare time to first absence by beryllium sensitization status. Finally, we examined beryllium status by occupational group. Results. Fewer than 3% of the 19,305 workers were BeS, and workers with BeS or CBD had more total absences (odds ratio [OR] = 1.31; 95% confidence interval [CI] = 1.18, 1.46) and respiratory absences (OR = 1.51; 95% CI = 1.24, 1.84) than did other workers. Time to first absence for all causes and for respiratory conditions occurred earlier for workers with BeS or CBD than for other workers. Line operators and crafts personnel were at increased risk for BeS or CBD. Conclusions. Although not considered "diseased," workers with BeS have higher absenteeism compared with nonsensitized workers.

Occupational exposure and mortality among workers at three titanium dioxide plants.

BACKGROUND: A cohort of 3,607 workers employed in three DuPont titanium dioxide production facilities was followed from 1935 through 2006. METHODS: Combined and plant-specific cohort mortality was compared with the overall US population and other DuPont employees. The relationships between selected causes of death and annual cumulative exposures to titanium dioxide and chloride were investigated using Poisson regression methods to examine trends with increasing exposure. RESULTS: Among the 833 deaths, no causes of deaths were statistically significantly elevated either overall or plant-specific when compared to the US population. Compared to DuPont workers, statistically significantly elevated SMRs for all causes, all cancers, and lung cancers were found driven by the workers at the oldest plant. Comparing increasing exposure groups to the lowest group, disease risk did not increase with exposure. CONCLUSIONS: There was no indication of a positive association between occupational exposure and death from all causes, all cancers, lung cancers, non-malignant respiratory disease, or all heart disease.

Mortality among titanium dioxide workers at three DuPont plants.

OBJECTIVE: To evaluate the mortality among workers employed at three titanium dioxide plants in the United States. METHODS: We expanded and updated a cohort employed at titanium dioxide plants. Cause-specific standardized mortality ratios (SMRs) were calculated combined and stratified by plant for workers employed at least 6 months between 1935 and 2005. RESULTS: No indications of excess mortality from any cause were found. All causes SMR increased with length of plant operation as did most cause-specific SMRs. With lung, the target organ of interest, no increases in malignant or nonmalignant respiratory disease were observed. CONCLUSIONS: The mortality rates are comparable with the general US population. Increasing SMRs with length of plant operation is indicative of waning healthy worker effect with time since first employment. The results are comparable with other titanium dioxide cohort studies.