External Radiation Exposure and Mortality in a Cohort of Uranium Processing Workers

Elizabeth Dupree-Ellis1, Janice Watkins1, J. Nicholas Ingle2 and Joyce Phillips1

1 Center for Epidemiologic Research, Oak Ridge Associated Universities, Oak Ridge, TN.
2 Delta 21 Resources, Inc., Oak Ridge, TN.


    ABSTRACT
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
In a study of 2,514 White male workers employed between 1942 and 1966 at a US uranium processing plant, mortality was compared with overall US mortality, and the relation between external ionizing radiation and cancer was evaluated. Through 1993, 1,013 deaths occurred. The mean cumulative dose was 47.8 mSv. The standardized mortality ratio (SMR) was 0.90 for all causes of death and 1.05 for all cancers. Many cancer sites had elevated SMRs. Among nonmalignant outcomes, the SMR for chronic nephritis was 1.88 (six deaths observed). An excess relative risk estimate of 10.5 per Sv (10 cases) was observed for kidney cancer; this may have resulted from chance, internal radiation, or chemical exposures not considered.

kidney; mortality; neoplasms, radiation-induced; occupational exposure; radiation, ionizing; risk

Abbreviations: SMR, standardized mortality ratio


    INTRODUCTION
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
During World War II, a network of Manhattan Engineer District/Atomic Energy Commission plants were involved in uranium production. Mallinckrodt Chemical Works (St. Louis, Missouri) processed tonnage quantities of uranium ore into pure uranium tetrafluoride and metal between 1943 and 1966. From 1946 through 1956, Mallinckrodt processed uranium ore from the Belgian Congo, which was assayed at up to 70 percent uranium, as compared with North American ore, which was less than 1 percent uranium. Because of its high uranium content, Congo ore contained up to 100 mg of radium per ton of ore. During processing, radium was concentrated up to 300 mg per ton. Processing operations, which produced both soluble and insoluble uranium compounds, were crude by modern standards. Daily average uranium dust concentrations of 100–200 times the maximum allowable concentration of 50 µg/m3 were measured in poorly ventilated processing areas. These conditions provided potential exposure to internal and external radiation, plus chemical toxicity from uranium. Nonradiologic hazards, including possible carcinogens, silica, and sulfuric acid, were present during processing (1Go, 2Go). Eisenbud (3Go) provided a good overview of the process, types of exposure, and industrial hygiene measures involved.

This retrospective cohort mortality study, considering external radiation dose, was the initial investigation into associations between occupational exposure and mortality. All solid tumors, leukemia, and multiple myeloma were of interest. Future mortality analyses will focus on internal radiation dose and chemical exposures.


    MATERIALS AND METHODS
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The cohort was enumerated using contemporary plant records. Vital status through 1993 was determined using Social Security Administration, Pension Benefit Information, and National Death Index databases.

From mid-1945 onward, workers wore film badges designed to monitor ß- and {gamma}-radiation exposure. Deep dose equivalent was used to calculate individual annual doses. For the 20.8 percent of working years for which monitoring results were unavailable, an algorithm was used to assign doses (4Go). Exposure to neutrons was unknown but was likely to have been minimal. Person-years were calculated from 30 days after the date of first hire until the earliest of either death, loss to follow-up, or study closing. Any worker known to be alive through 1978 was assumed to be alive through the end of the study if the National Death Index gave no indication of death. Underlying cause of death was used to calculate standardized mortality ratios (SMRs) comparing cohort mortality with that of US White males. Nonunderlying cancer causes were included in dose-response analyses.

Dose-response analyses were stratified on age and calendar period, utilizing an internal comparison group and time-dependent cumulative dose groups with doses lagged 10 years (2 years for leukemia). Dose-response estimates, expressed as excess relative risk per Sv, were modeled as 1 + ß x dose. Maximum likelihood parameter estimates and likelihood-based confidence intervals were calculated using Poisson regression and Epicure (5Go). For smoking, the relations between radiation dose and smoking-related cancers (6Go), nonmalignant respiratory diseases (excluding pneumonia), and circulatory diseases were evaluated. For alcohol use, liver cirrhosis was similarly evaluated.


    RESULTS
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Of 3,259 workers, 2,514 were included in the study. Of the 745 workers excluded, 556 (74.6 percent) were women, and 43 (5.8 percent) were men of color. Work history records and interviews with former workers confirmed that these groups had minimal potential for external radiation exposure.

On average, a worker was hired in 1951 at the age of 30.3 years and worked at Mallinckrodt for 5.2 years. Two thirds of workers were hired before pitchblende processing ended. The mean length of follow-up was 34.6 years (median, 36 years). Over 90 percent of the workers were followed for at least 20 years. Through 1993, 87,757 person-years accumulated; 1,013 workers died (40.3 percent), and death certificates were obtained for 1,012 (99.9 percent). The mean age at death was 64.7 years (median, 66 years) after 29.1 years of follow-up (median, 30 years). Among the 1,501 workers not known to be deceased, 45 were lost to follow-up before the National Death Index was begun in 1979. The distribution of cumulative external radiation doses is given in table 1. Mean cumulative whole body exposure was 47.8 mSv (median, 15.3 mSv), with a population dose of 120,063 mSv.


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TABLE 1. Cumulative external radiation dose, with no lagging, among 2,514 White males who were employed for at least 30 days at the Mallinckrodt Chemical Works between 1942 and 1966

 
Tables 2 and 3 present results of SMR analyses for selected noncancer and cancer causes of death, respectively. The SMR for all causes of death (SMR = 0.90; 95 percent confidence interval: 0.85, 0.96) was significantly below 1.00. The SMR for all cancers, based on 283 deaths, was 1.05 (95 percent confidence interval: 0.93, 1.17), and many of the site-specific SMRs were elevated. Cancer sites with at least a 30 percent excess over expected mortality were esophagus, rectum, brain, and multiple myeloma. Among the nonmalignant outcomes, only chronic nephritis exhibited such an excess. Driven by four deaths in the highest dose group, the excess relative risk for kidney cancer was 10.5 per Sv (90 percent confidence interval: 0.6, 57.4). The observed:expected ratios for kidney cancer by dose were as follows: <5 mSv, 3:2.4; 5–9 mSv, 0:0.9; 10–19 mSv, 0:1.3; 20–39 mSv, 2:1.4; 40–79 mSv, 1:1.5; 80–159 mSv, 0:1.3; and >=160 mSv, 4:1.2.


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TABLE 2. Standardized mortality ratios for selected causes of death among 2,514 White males employed at the Mallinckrodt Chemical Works, adjusted for age and calendar period, 1942–1993

 

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TABLE 3. Standardized mortality ratios for selected cancer sites among 2,514 White males employed at the Mallinckrodt Chemical Works, adjusted for age and calendar period, 1942–1993

 

    DISCUSSION
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
A number of studies have investigated the relation between mortality and occupational external ionizing radiation among nuclear workers (7GoGoGoGoGoGo–13Go). The average cumulative radiation dose in these studies was similar to that in the current study. However, the percentage of workers who were deceased and the duration of follow-up were substantially greater here than in other studies. Like the current study, all-cause SMRs were reduced, indicating the presence of the healthy worker effect. The all-cancer SMR was greater than expected in only two other studies (10Go, 12Go). Significantly increased SMRs were reported for lung, pleural, and thyroid cancers (9Go, 10Go, 13Go). Collectively, these studies reported elevated SMRs for 11 additional site-specific cancers included in the current study (7GoGoGoGoGo–12Go). Significant positive dose-response trends were found only for lung cancer (7Go), melanoma and other skin cancer (9Go), multiple myeloma (8Go), leukemia (8Go, 9Go), and all lymphatic and hematopoietic cancers (13Go). In the current study, an increase in the all-cancer SMR resulted from increases in 13 site-specific cancers.

The only indication of a dose-response relationship was between kidney cancer and external radiation. Because 26 outcomes were evaluated, this result may have occurred by chance. Of the five occupational radiation studies that investigated a dose-response relationship for kidney cancer (7GoGo–9Go, 11Go, 13Go), only one found a positive relation (11Go). A positive relation was reported for patients treated with ionizing radiation with regard to ankylosing spondylitis and cervical cancer (14Go, 15Go). However, studies of atomic bomb survivors failed to identify a relation with kidney cancer (16Go).

Risk factors that have been identified for kidney cancer include smoking, use of phenacetin or diuretics, obesity, high protein intake, asbestos exposure, and ionizing radiation (17Go). Two of the 10 men who died of kidney cancer (eight underlying cases and two nonunderlying cases) had held jobs with possible asbestos exposure. Although information on smoking was not available, indirect methods revealed no indication of a relation between smoking and radiation exposure.

External radiation exposure during pitchblende processing was potentially high, because most operations were done manually. Seven men who died of kidney cancer had worked in the pitchblende processing area, six in jobs involving the processing of uranium prior to removal of radium; four of these workers had cumulative external radiation doses of 185 mSv or greater.

Internal radiation exposure or the chemical toxicity of uranium may be responsible for the study findings. Solubility of uranium compounds varied across processing steps and affected clearance time from the lung, the primary exposure route. Increasing solubility decreases the lung clearance rate, which decreases radiation hazard but increases renal toxicity (18Go, 19Go). The excess deaths from chronic nephritis increase the importance of considering other exposures. Silica, which made up 15–50 percent of the ore, has been associated with chronic renal disease in gold miners (20Go, 21Go). Four of seven workers with chronic nephritis and three workers with kidney cancer had worked in jobs at the beginning of the process, with some of the highest dust concentrations and prior to removal of silica from the ore (3Go).

Because of the inconsistent application of specific renal disease codes from the International Classification of Diseases over time, the elevated chronic nephritis SMR may have resulted from a bias in assigning these codes. When other possible classifications for renal disease were considered, specifically pyelonephritis and hypertensive nephrosclerosis, three additional deaths were identified. Depending on the direction of any misclassification in the renal disease deaths, the value of the SMR could increase or decrease.

Other weaknesses in this study include the small cohort size, a possible bias in assignment of person-years from unidentified deaths, and incomplete personal monitoring records on external radiation. A study by Calle and Terrill (22Go) found that the number of missed deaths resulting from National Death Index assumptions was likely to be small, and any bias in person-years assignment was minimal. The small cohort size could be addressed by pooling this study cohort with others from similar uranium processing operations. Uranium processing operations at the Fernald site (Cincinnati, Ohio), which were designed by Mallinckrodt engineers, represented a modernization of Mallinckrodt's operations. Since both facilities had similar industrial hygiene and health physics programs, radiation dose estimates should be compatible. Combining these cohorts would almost triple the size of the Mallinckrodt cohort, increasing statistical power.

Despite this study's limitations, over 90 percent of the cohort were followed for at least 20 years, allowing sufficient time for occupationally induced cancers to develop. The dose-response relationship suggested between external radiation and kidney cancer was validated by the job histories of the cases, but it must be considered provisional until further research investigates the relations with internal radiation dose and the chemical toxicity of uranium.


    ACKNOWLEDGMENTS
 
This research was supported by contract 200-93-2695 from the US Department of Health and Human Services.

The authors acknowledge the vital statistics offices of the individual states as the sources of death record data, and they appreciate the offices' technical support of this research.


    NOTES
 
Reprint requests to Dr. Elizabeth Dupree-Ellis, Oak Ridge Associated Universities, Center for Epidemiologic Research, P.O. Box 117, MS 45, Oak Ridge, TN 37830-0117.


    REFERENCES
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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Received for publication March 5, 1999. Accepted for publication March 13, 2000.