Third mortality follow-up of the Mallinckrodt uranium processing workers, 1942-2019.

INTRODUCTION: Mallinckrodt Chemical Works was a uranium processing facility during the Manhattan Project from 1942 to 1966. Thousands of workers were exposed to low-dose-rates of ionizing radiation from external and internal sources. This third follow-up of 2514 White male employees updates cancer and noncancer mortality potentially associated with radiation and silica dust. MATERIALS AND METHODS: Individual, annualized organ doses were estimated from film badge records (n monitored = 2514), occupational chest x-rays (n = 2514), uranium urinalysis (n = 1868), radium intake through radon breath measurements (n = 487), and radon ambient measurements (n = 1356). Silica dust exposure from pitchblende processing was estimated (n = 1317). Vital status and cause of death determination through 2019 relied upon the National Death Index and Social Security Administration Epidemiological Vital Status Service. The analysis included standardized mortality ratios (SMRs), Cox proportional hazards, and Poisson regression models. RESULTS: Vital status was confirmed for 99.4% of workers (84.0% deceased). For a dose weighting factor of 1 for intakes of uranium, radium, and radon decay products, the mean and median lung doses were 65.6 and 29.9 mGy, respectively. SMRs indicated a difference in health outcomes between salaried and hourly workers, and more brain cancer deaths than expected [SMR: 1.79; 95% confidence interval (CI): 1.14, 2.70]. No association was seen between radiation and lung cancer [hazard ratio (HR) at 100 mGy: 0.93; 95%CI: 0.78, 1.11]. The relationship between radiation and kidney cancer observed in the previous follow-up was maintained (HR at 100 mGy: 2.07; 95%CI: 1.12, 3.79). Cardiovascular disease (CVD) also increased significantly with heart dose (HR at 100 mGy: 1.11; 95%CI: 1.02, 1.21). Exposures to dust ≥23.6 mg/m3-year were associated with nonmalignant kidney disease (NMKD) (HR: 3.02; 95%CI: 1.12, 8.16) and kidney cancer combined with NMKD (HR: 2.46; 95%CI: 1.04, 5.81), though without evidence of a dose-response per 100 mg/m3-year. CONCLUSIONS: This third follow-up of Mallinckrodt uranium processors reinforced the results of the previous studies. There was an excess of brain cancers compared with the US population, although no radiation dose-response was detected. The association between radiation and kidney cancer remained, though potentially due to few cases at higher doses. The association between levels of silica dust ≥23.6 mg/m3-year and NMKD also remained. No association was observed between radiation and lung cancer. A positive dose-response was observed between radiation and CVD; however, this association may be confounded by smoking, which was unmeasured. Future work will pool these data with other uranium processing worker cohorts within the Million Person Study.

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.

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.

Cancer incidence and mortality in populations living near uranium milling and mining operations in grants, New Mexico, 1950-2004.

In a previous cohort study of workers engaged in uranium milling and mining activities near Grants, Cibola County, New Mexico, we found lung cancer mortality to be significantly increased among underground miners. Uranium mining took place from early in the 1950s to 1990, and the Grants Uranium Mill operated from 1958-1990. The present study evaluates cancer mortality during 1950-2004 and cancer incidence during 1982-2004 among county residents. Standardized mortality (SMR) and incidence (SIR) ratios and 95% confidence intervals (CI) were computed, with observed numbers of cancer deaths and cases compared to expected values based on New Mexico cancer rates. The total numbers of cancer deaths and incident cancers were close to that expected (SMR 1.04, 95% CI 1.01-1.07; SIR 0.97, 95% CI 0.92-1.02). Lung cancer mortality and incidence were significantly increased among men (SMR 1.11, 95% CI 1.02-1.21; SIR 1.40, 95% CI 1.18-1.64) but not women (SMR 0.97, 95% CI 0.85-1.10; SIR 1.01, 95% CI 0.78-1.29). Similarly, among the population of the three census tracts near the Grants Uranium Mill, lung cancer mortality was significantly elevated among men (SMR 1.57; 95% CI 1.21-1.99) but not women (SMR 1.12; 95% CI 0.75-1.61). Except for an elevation in mortality for stomach cancer among women (SMR 1.30; 95% CI 1.03-1.63), which declined over the 55-year observation period, no significant increases in SMRs or SIRs for 22 other cancers were found. Although etiological inferences cannot be drawn from these ecological data, the excesses of lung cancer among men seem likely to be due to previously reported risks among underground miners from exposure to radon gas and its decay products. Smoking, socioeconomic factors or ethnicity may also have contributed to the lung cancer excesses observed in our study. The stomach cancer increase was highest before the uranium mill began operation and then decreased to normal levels. With the exception of male lung cancer, this study provides no clear or consistent evidence that the operation of uranium mills and mines adversely affected cancer incidence or mortality of county residents.

Cancer incidence in municipalities near two former nuclear materials processing facilities in Pennsylvania--an update.

Previous studies of cancer incidence among persons living in municipalities within one mile of two nuclear materials processing and fabrication plants in Pennsylvania were extended for the years 1998-2004. It had been shown that mailing addresses for residents of rural areas often did not reflect the actual municipality of residence and, if not corrected, would bias study results. The previous studies had corrected for this bias. Accordingly for the extended study, we obtained mailing addresses from the Pennsylvania Department of Health (PDH) for 866 persons with cancer who presumably lived in one of eight minor civil divisions (MCDs) near or encompassing the former nuclear facilities, designated as Area 1 in previous studies conducted by the PDH. Street addresses were geocoded and local postmasters were asked to place rural delivery addresses, post office boxes and street addresses that could not be geocoded into the correct MCD of actual residence. Over 15% of the mailing addresses were found not to be within the boundaries of the Area 1 municipalities. After the mailing addresses of individuals with cancer were placed in their proper MCD of residence, the number of persons diagnosed with cancer (n = 708) and confirmed to have lived in Area 1 was as expected (728.4) based on cancer incidence rates in the general population of Pennsylvania (SIR 0.97; 95% CI 0.90-1.05). To further evaluate the patterns of cancer rates near these nuclear facilities and the influence of improved reporting and geocoding of addresses over time, analyses were conducted of publicly available cancer incidence data from 1990 through 2004. Based on mailing addresses, a steady decrease in the number of cancers reported in the Area 1 proximal MCDs was seen, in contrast to a steady rise in the number of cancers reported in seven adjacent but more distant MCDs from the nuclear facilities, designated as Area 2. These patterns were attributed to improvements over time in the geocoding of residential mailing addresses coupled with the gradual elimination and replacement of rural delivery addresses with street addresses. The incorrect placement of mailing addresses in residential Area 1 municipalities prior to about 2002 overestimated the number of cancers occurring among residents living in close proximity to the nuclear facilities and, correspondingly, underestimated the number among Area 2 residents. Summing Area 1 and Area 2 data showed that there was no change in cancer rates over time. These results are consistent with previous studies indicating that living in municipalities near the former Apollo-Parks nuclear facilities was not associated with an increase in cancer occurrence.

County mortality and cancer incidence in relation to living near two former nuclear materials processing facilities in Pennsylvania--an update.

A previous county mortality study of populations living near two nuclear materials processing and fabrication facilities in Westmoreland and Armstrong counties in Pennsylvania (1950-1995) was extended through 2004. Noncancer mortality (1996-2004) and cancer incidence (1990-2004) were also evaluated. Among the Westmoreland and Armstrong populations, 10,547 cancer deaths occurred during the period 1996 through 2004 and the relative risk (RR) based on comparisons with six demographically similar counties in western Pennsylvania was 0.97, that is, almost exactly as expected, and no different from our previously published analyses covering the years 1950-1995. The results based on cancer incidence data were very similar to those based on cancer mortality data. Over the years 1990 though 2004, 39,350 incident cancers were reported among residents of Armstrong and Westmoreland counties and the RR based on the six demographically similar counties was 0.99, that is, almost exactly as expected. The number of deaths from nonmalignant conditions was 36,565 and very close to the number expected (RR 1.01). Overall, no increases in cancer or nonmalignant diseases could be attributed to living in counties with nuclear materials processing and fabrication facilities.

A cohort study of uranium millers and miners of Grants, New Mexico, 1979-2005.

A cohort mortality study of workers engaged in uranium milling and mining activities near Grants, New Mexico, during the period from 1955 to 1990 was conducted. Vital status was determined through 2005 and standardised mortality ratio (SMR) analyses were conducted for 2745 men and women alive after 1978 who were employed for at least six months. Overall, mortality from all causes (SMR 1.15; 95% CI 1.07-1.23; n = 818) and all cancers (SMR 1.22; 95% CI 1.07-1.38; n = 246) was greater than expected on the basis of US mortality rates. Increased mortality, however, was seen only among the 1735 underground uranium miners and was due to malignant (SMR 2.17; 95% CI 1.75-2.65; n = 95) and non-malignant (SMR 1.64; 95% CI 1.23-2.13; n = 55) respiratory diseases, cirrhosis of the liver (SMR 1.79; n = 18) and external causes (SMR 1.65; n = 58). The lung cancer excess likely is attributable to the historically high levels of radon in uranium mines of the Colorado Plateau, combined with the heavy use of tobacco products. No statistically significant elevation in any cause of death was seen among the 904 non-miners employed at the Grants uranium mill. Among 718 mill workers with the greatest potential for exposure to uranium ore, no statistically significant increase in any cause of death of a priori interest was seen, i.e., cancers of the lung, kidney, liver, or bone, lymphoma, non-malignant respiratory disease, renal disease or liver disease. Although the population studied was relatively small, the follow-up was long (up to 50 yrs) and complete. In contrast to miners exposed to radon and radon decay products, for uranium mill workers exposed to uranium dusts and mill products there was no clear evidence of uranium-related disease.

Mortality among residents of Uravan, Colorado who lived near a uranium mill, 1936-84.

A cohort mortality study was conducted of all adult residents who ever lived in Uravan, Colorado, a company town built around a uranium mill. Vital status was determined through 2004 and standardised mortality analyses conducted for 1905 men and women alive after 1978 who lived for at least 6 months between 1936 and 1984 in Uravan. Overall, mortality from all causes (standardised mortality ratio (SMR) 0.90) and all cancers (SMR 1.00) was less than or as expected based on US mortality rates. Among the 459 residents who had worked in underground uranium mines, a significant increase in lung cancer was found (SMR 2.00; 95% CI 1.39-2.78). No significant elevation in lung cancer was seen among the 767 female residents of Uravan or the 622 uranium mill workers. No cause of death of a priori interest was significantly increased in any group, i.e. cancers of the kidney, liver, breast, lymphoma or leukaemia or non-malignant respiratory disease, renal disease or liver disease. This community cohort study revealed a significant excess of lung cancer among males who had been employed as underground miners. We attribute this excess to the historically high levels of radon in uranium mines of the Colorado Plateau, coupled with the heavy use of tobacco products. There was no evidence that environmental radiation exposures above natural background associated with the uranium mill operations increased the risk of cancer. Although the population studied was relatively small, the follow-up was long, extending up to 65 years after first residence in Uravan, and nearly half of the study subjects had died.

Cancer and noncancer mortality in populations living near uranium and vanadium mining and milling operations in Montrose County, Colorado, 1950-2000.

Mining and milling of uranium in Montrose County on the Western Slope of Colorado began in the early 1900s and continued until the early 1980s. To evaluate the possible impact of these activities on the health of communities living on the Colorado Plateau, mortality rates between 1950 and 2000 among Montrose County residents were compared to rates among residents in five similar counties in Colorado. Standardized mortality ratios (SMRs) were computed as the ratio of observed numbers of deaths in Montrose County to the expected numbers of deaths based on mortality rates in the general populations of Colorado and the United States. Relative risks (RRs) were computed as the ratio of the SMRs for Montrose County to the SMRs for the five comparison counties. Between 1950 and 2000, a total of 1,877 cancer deaths occurred in the population residing in Montrose County, compared with 1,903 expected based on general population rates for Colorado (SMR(CO) 0.99). There were 11,837 cancer deaths in the five comparison counties during the same 51-year period compared with 12,135 expected (SMR(CO) 0.98). There was no difference between the total cancer mortality rates in Montrose County and those in the comparison counties (RR = 1.01; 95% CI 0.96-1.06). Except for lung cancer among males (RR = 1.19; 95% CI 1.06-1.33), no statistically significant excesses were seen for any causes of death of a priori interest: cancers of the breast, kidney, liver, bone, or childhood cancer, leukemia, non-Hodgkin lymphoma, renal disease or nonmalignant respiratory disease. Lung cancer among females was decreased (RR = 0.83; 95% CI 0.67-1.02). The absence of elevated mortality rates of cancer in Montrose County over a period of 51 years suggests that the historical milling and mining operations did not adversely affect the health of Montrose County residents. Although descriptive correlation analyses such as this preclude definitive causal inferences, the increased lung cancer mortality seen among males but not females is most likely due to prior occupational exposure to radon and cigarette smoking among underground miners residing in Montrose County, consistent with previous cohort studies of Colorado miners and of residents of the town of Uravan in Montrose County.

Cancer incidence in municipalities near two former nuclear materials processing facilities in Pennsylvania.

Because nuclear facilities can release radionuclides into the surrounding environment accidentally or during normal operations, there has been public concern over the possibility of adverse health effects. Two former nuclear materials processing facilities in Armstrong County Pennsylvania have been the focus of such public concern for over 20 y. The Apollo and Parks facilities processed uranium and plutonium fuels for use in nuclear applications. To evaluate the possibility of increased cancer rates in the communities near the Apollo-Parks nuclear processing materials plants, cancer incidence rates were assessed for the years 1993-1997, or nearly 40 y after the plants had begun operation in 1957 and 1960, respectively. The rates of cancer were evaluated among the approximately 17,000 persons living in 1 of 8 municipalities encompassing or near these nuclear sites. Numbers of cancers and mailing addresses (n = 935) were obtained from the Pennsylvania Department of Health. Because mailing addresses in small rural areas do not always reflect actual residences within a municipality, each of 935 addresses was validated (and corrections made when indicated) by contacting area postmasters and using Census Bureau geocoding information, street maps, and aerial photographs. Standardized Incidence Ratios (SIRs) were computed as the ratio of observed numbers of cancers in the study area compared to the expected number derived from general population rates of Pennsylvania. Forty percent of the mailing addresses were found not to be within the boundaries of the study municipalities. After excluding these persons who did not reside in one of the eight municipalities near the Apollo-Parks facilities, 581 cancers remained in contrast to 574.0 expected (SIR 1.01; 95% confidence interval 0.93-1.10). Based upon knowledge of the tissues where uranium or plutonium likely would be deposited after intake, cancers of the lung (SIR 0.88), kidney (SIR 1.05), non-Hodgkin's lymphoma (SIR 1.10), liver (SIR 0.61), and bone (2 observed vs. 1.19 expected) were carefully evaluated, but no significant excesses were noted at these sites. Cancers of the female breast and thyroid and leukemia also were not significantly increased, as expected since these tissues are not sites where uranium or plutonium would concentrate. Overall, no increase in cancer risk could be attributed to living near the two former nuclear materials processing facilities. However, misleading elevations in cancer risks would have been suggested if mailing addresses had not been corrected to exclude addresses that were not within the boundaries of the municipalities for which population data were available. The study had sufficient power to exclude increased cancer risks of 10% or greater.

Cancer mortality in counties near two former nuclear materials processing facilities in Pennsylvania, 1950-1995.

There has been concern that living near nuclear installations might increase the risk of cancer, including childhood leukemia, in surrounding communities. Such concern has been voiced by residents in Armstrong and Westmoreland Counties in Western Pennsylvania in conjunction with the operation of two former nuclear materials processing facilities located in the Apollo borough and the Parks township, just three miles apart. These facilities began operating in 1957 and 1960 and processed uranium and plutonium for commercial and naval applications. To evaluate the possibility of increased cancer rates in communities around the Apollo-Parks nuclear facilities, a cancer incidence and a cancer mortality survey were conducted. The county mortality findings are reported here. Nearly 40,000 cancer deaths occurred in the population residing in Armstrong and Westmoreland Counties from 1950 through 1995. Each of these two study counties was matched for comparison to three control counties in the same region on the basis of age, race, urbanization, and socioeconomic factors available from the 1990 U.S. Census. There were over 77,000 cancer deaths in the 6 control counties during the 45 y studied. Following similar methods used by the National Cancer Institute, Standardized Mortality Ratios (SMRs) were computed as the ratio of observed numbers of cancers in the study and control counties compared to the expected number derived from general population rates of the United States. Relative risks (RR) were computed as the ratios of the SMRs for the study and the control counties. There were no significant increases in the study counties for any cancer when comparisons were made with either the U.S. population or the control counties. In particular, deaths due to cancers of the lung, bone, liver, and kidney were not more frequent in the study counties than in the control counties. These are the cancers of a priori interest given that uranium and/or plutonium might be expected to concentrate in these tissues. Deaths from all cancers combined also were not increased in the study counties, and the RRs of cancer mortality before the facilities operated (1950-1964), during plant operations (1965-1980) and after plant closure (1980-1995) were similar: 0.96, 0.95 and 0.98, respectively. For childhood leukemia mortality, the relative risk comparing the study counties with their controls before plant start-up was 1.02, while during operations (RR 0.81) and after closure (RR 0.57) the relative risks were lower. The study is limited by the correlational approach and the relatively large size of the geographic areas of the counties studied.