Uranium Processing Workers (UPW)

The proposed pooled analysis of workers at four uranium processing facilities is positioned to address critical gaps in knowledge of the long-term health risks associated with occupational exposure to uranium, radium and silica. Over 12,700 workers from the US and Canada are available for study and 
dose-response evaluations. The unifying feature of these four cohorts is that they all belonged to a network of plants that provided the uranium needed by the United States during World War II, and for several years thereafter. The facilities in the US include the Mallinckrodt Chemical Works in Missouri, the Middlesex Sampling Plant in New Jersey, and the Fernald Feed Materials Production Center in Ohio. The facility in Canada is the Port Hope radium and uranium refinery and processing plant. Employment began as early as the 1930s and all of the facilities processed high grade uranium pitchblende ore obtained from the Belgium Congo which contained high concentrations of radium, soluble and insoluble uranium compounds and other chemical compounds. While the processing of uranium ore involved exposures to external radiation (e.g. gamma (γ)-rays) and to radon decay products (RDP), it is the ingestion of radioactive ore dust containing uranium, radium and silica that sets these cohorts apart from others. The chemical toxicity of uranium, a heavy metal, is also an industrial hygiene concern. There is limited evidence in humans for the carcinogenicity of mixtures of uranium isotopes from the nuclear fuel cycle,5-8 but there is an emerging consensus that exposures of uranium processors are substantially different from those of other workers of the nuclear fuel cycle, and that they should be carefully evaluated in separate studies.

Why is this important? Exposure to radium, which decays by emitting high linear energy-transfer (LET) alpha particles, is what makes these four cohorts relevant to current-day exposure scenarios. One of the major concerns of the National Atmospheric and Space Administration (NASA) in space missions to Mars is the effect of high-LET radiation on brain tissue and the possibility of cognitive dysfunction and long-term dementia related to long-term missions.9 The uranium processing cohorts provide the closest human analogue to the circumstances in deep space. The cohorts share many similarities in occupational exposures, dose estimation and study design methods and background population mortality rates,10-12 providing a strong rationale for conducting a pooled study. It will be the largest study to date to examine health risks from uranium processing and will provide more accurate risk estimates than individual studies - before new and more costly studies are undertaken. We propose to estimate radium exposures from radon breathe analyses, detailed job histories, and job- specific time-weighted averages of ore dust (silica) exposures. Urine samples, film badge readings, and dust and radon decay product measurements will be used to estimate organ-specific radiation doses and concomitant silica and heavy metal exposure. Previously estimated γ-ray and RDP doses will be combined and processed in a similar fashion for pooled analyses. Main analyses will be based on the pooled cohort of ~11,200 men, but we will also conduct exploratory analyses of ~1,500 women involved in uranium 
processing. Over (60%) of the population has died and follow-up is >60 years. Accordingly, we have the following specific aims:

Aim 1: To complete the radiation dosimetry for Middlesex (from film badge readings, occupational medical x- rays, radon breath analyses, and radium and uranium urine samples), and estimate silica dust and radium exposures for workers at four uranium processing facilities: Port Hope, Fernald, Mallinckrodt and Middlesex.

Aim 2: To examine radiation-related risks of mortality from site-specific cancers and causes of death. To estimate radiation-related risks of morbidity from cardiovascular and renal diseases from exposures to uranium and radium. To estimate risk of lung and kidney disease from cumulative silica inhalation.

Aim 3: To estimate the risk of mortality from dementia, Alzheimer’s disease, Parkinson’s disease, and motor neuron disease associated with radium dose to brain.

Our team is comprised of the Principal Investigators of the Canadian and US cohorts, and the research team is further strengthened by a specialist in large pooled analyses (Dr. J. Boice, Jr.). The pooled analysis will bring clarity to all of these questions because of the large size, the long follow-up, the individual dose assessments and the similarity in radiation exposures between the four cohorts. Study findings will be uniquely relevant to the U.S. workers employed in the uranium processing industry and to astronauts exposed to cosmic radiation on long inter-planetary missions. This work will facilitate the preparation of a common research protocol and the verification of the feasibility of the international pooled analysis of uranium processing workers.