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

Abstract

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.

Keywords:

• Radiation
• epidemiology
• occupational exposures
• uranium
• uranium processing workers

Acknowledgments

The authors would like to recognize the contributions of everyone who has made this work possible through their consultation and participation in the Million Person Study. In particular, we would like to thank Dr. Loren Lipworth and Dr. Melinda Aldrich, who provided valuable insights on this paper as members of CMM’s dissertation committee, Mr. David Girardi, who helped considerably with data preparation, and Dr. Dale Preston, who took many hours out of his day to teach CMM the intricacies of Epicure.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The datasets generated during and/or analyzed during the current study will be available in the Comprehensive Epidemiologic Data Resource (CEDR) repository, https://oriseapps.orau.gov/cedr/.

Additional information

Funding

This work was supported in part by grants awarded to the National Council on Radiation Protection and Measurements from the U.S. Department of Energy [grant numbers DE-AU0000042 and DE-AU0000046]. Contract support was additionally received by Oak Ridge National Laboratory from the Office of Radiation and Indoor Air, U.S. Environmental Protection Agency through Interagency Agreement [DOE No. 1824 S581-A1], under contract number DE-AC05-00OR22725 with UT-Battelle. Contract support was also received by Oak Ridge Associated Universities from the U.S. Department of Energy through contract number DE-SC0014664. Dr. Zablotska’s work was funded by National Institute for Occupational Safety and Health and National Institutes of Health award [5R21OH011452] (Principal Investigator: L.B. Zablotska).

Notes on contributors

Cato M. Milder

Cato M. Milder is a postdoctoral fellow in the National Cancer Institute’s Division of Cancer Epidemiology and Genetics in the Radiation Epidemiology Branch. He graduated with a PhD in Epidemiology from Vanderbilt University, where he focused on long-term health effects following occupational exposures to ionizing radiation. Dr. Milder has worked with a variety of cohorts exposed to radiation occupationally and environmentally, including astronauts, nuclear workers, and atomic bomb survivors.

Sara C. Howard

Sara C. Howard is a research associate at Oak Ridge Associated Universities. She has an MPH and is currently pursuing a PhD in epidemiology with a focus on chronic diseases and occupational exposure. She has been a collaborator on the Million Person Study of Low-Dose Health Effects for nearly three years.

Elizabeth D. Ellis

Elizabeth D. Ellis is an occupational epidemiologist at Oak Ridge Associated Universities. She has been studying the health effects of chronic low dose ionizing radiation on the Department of Energy nuclear workers for over 40 years and has been a collaborator on the MPS for over 10 years. She was a member of an International Commission of Radiation Protection Task Group reviewing the health effects of alpha emitters. She is also active in protection of human participants in research serving on several Institutional Review Boards.

Ashley P. Golden

Ashley P. Golden is a biostatistician and project manager at Oak Ridge Associated Universities where she conducts multidisciplinary projects in occupational epidemiology, radiation exposure and dosimetry, medical surveillance, and environmental assessments. She has been a collaborator on the Million Person Study of Low-Dose Health Effects for six years.

Sarah S. Cohen

Sarah S. Cohen is a Senior Managing Epidemiologist at EpidStrategies, a division of ToxStrategies, Inc. She has been a collaborator on the Million Person Study of Low-Dose Health Effects for nearly twenty years.

Michael T. Mumma

Michael T. Mumma is the Director of Information Technology at the International Epidemiology Institute and the International Epidemiology Field Station for Vanderbilt University Medical Center. He has over 20 years of experience in data analysis and conducting epidemiologic investigations.

Richard W. Leggett

Richard W. Leggett is a research scientist in the Environmental Sciences Division at Oak Ridge National Laboratory. His physiological systems models of the human circulation, skeleton, and gastrointestinal transfer and systemic biokinetic models for many elements are used by the International Commission on Radiological Protection as dosimetry and bioassay models.

Benjamin French

Benjamin French, PhD, is an Associate Professor in the Department of Biostatistics at Vanderbilt University Medical Center, Nashville, Tennessee.

Lydia B. Zablotska

Lydia B. Zablotska is Salvatore Pablo Lucia Professor of Epidemiology and Public Health in the Department of Epidemiology and Biostatistics in the School of Medicine at the University of California, San Francisco (UCSF), where she serves as the Leader of the Occupational and Environmental Epidemiology Area of Concentration. Dr. Zablotska is a physician and epidemiologist with extensive training and publications in radiation epidemiology, biostatistics, and risk modeling. Her research activities have focused primarily on the examination of risks of radiation exposures in various occupational and environmental settings. Dr. Zablotska’s work has clarified the understanding of the effects of occupational radiation exposures on health risks of nuclear power industry workers and workers of the uranium fuel production cycle in various occupational cohorts from the United States and Canada.

John D. Boice

John D. Boice, Jr. is the Director of Science at the National Council on Radiation Protection and Measurements and Professor of Epidemiology at Vanderbilt University. He served on the Main Commission of the International Commission on Radiological Protection and on the United Nations Scientific Committee on the Effects of Atomic Radiation. He directs the Million Person Study of Low-Dose Health Effects.