Ashley P Golden1, Elizabeth D Ellis1, Sarah S Cohen2, Michael T Mumma3, Richard W Leggett4, Phillip W Wallace1, David Girardi1, Janice P Watkins1, Roy E Shore5,6, John D Boice7,8. 1. Oak Ridge Associated Universities, Oak Ridge, TN, USA. 2. EpidStat Institute, Ann Arbor, MI, USA. 3. International Epidemiology Institute, Rockville, MD, USA. 4. Oak Ridge National Laboratory, Oak Ridge, TN, USA. 5. Epidemiology Division, New York University School of Medicine, NewYork, NY, USA. 6. Radiation Effects Research Foundation, Hiroshima, Japan. 7. National Council on Radiation Protection and Measurements, Bethesda, MD, USA. 8. Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.
Abstract
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.
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.