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Objective: This follow-up study of uranium processing workers at the Fernald Feed Materials Production Center examines the relationship between radiation exposure and cancer and non-cancer mortality among 6403 workers employed for at least 30 days between 1951 and 1985., Methods: We estimated cumulative, individual, annualised doses to 15 organs/tissues from external, internal and radon exposures. Vital status and cause of death were ascertained in 2017. The analysis employed standardised mortality ratios, Cox proportional hazards and Poisson regression models. Competing risk analysis was conducted for cardiovascular disease (CVD) mortality risk given several assumptions about risk independent of competing outcomes. Emphysema was examined to assess the potential for confounding by smoking., Results: Vital status was confirmed for 98.1% of workers, with 65.1% deceased. All-cause mortality was less than expected in salaried but not hourly workers when compared with the US population. A statistically significant dose response was observed between external (but not total or internal) lung dose and lung cancer mortality (HR at 100 mGy adjusted for internal dose=1.45; 95% CI=1.05 to 2.01). Significantly increased HRs at 100 mGy dose to heart were observed for CVD (1.27; 95% CI=1.07 to 1.50) and ischaemic heart disease (1.30; 95% CI=1.07 to 1.58). CVD risk remained elevated regardless of competing risk assumptions. Both external and internal radiation were associated with emphysema., Conclusions: Lung cancer was associated with external dose, though positive dose responses for emphysema imply residual confounding by smoking. Novel use of competing risk analysis for CVD demonstrates leveraging retrospective data for future risk prediction., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Radiation is one of the most important stressors related to missions in space beyond Earth's orbit. Epidemiologic studies of exposed workers have reported elevated rates of Parkinson's disease. The importance of cognitive dysfunction related to low-dose rate radiation in humans is not defined. A meta-analysis was conducted of six cohorts in the Million Person Study (MPS) of low-dose health effects to learn whether there is consistent evidence that Parkinson's disease is associated with radiation dose to brain., Materials and Methods: The MPS evaluates all causes of death among U.S. radiation workers and veterans, including Parkinson's disease. Systematic and consistent methods are applied to study all categories of workers including medical radiation workers, industrial radiographers, nuclear power plant workers, atomic veterans, and Manhattan Projects workers at the Los Alamos National Laboratory and at Rocky Flats. Consistent methods for all cohorts are used to estimate organ-specific doses and to obtain vital status and cause of death., Results: The meta-analysis include 6 cohorts within the MPS, consisting of 517,608 workers and 17,219,001 person-years of observation. The mean dose to brain ranged from 6.9 to 47.6 mGy and the maximum dose from 0.76 to 2.7 Gy. Five of the 6 cohorts revealed positive associations with Parkinson's disease. The overall summary estimate from the meta-analysis was statistically significant based on 1573 deaths due to Parkinson's disease. The summary excess relative risk at 100 mGy was 0.17 (95% CI: 0.05; 0.29)., Conclusions: Parkinson's disease was positively associated with radiation in the MPS cohorts indicating the need for careful evaluation as to causality in other studies, delineation of possible mechanisms, and assessing possible implications for space travel as well as radiation protection guidance for terrestrial workers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The content of this article does not necessarily represent the views of the National Council on Radiation Protection and Measurements, Vanderbilt University Medical Center, Memorial Sloan Kettering Cancer Center, U.S. Department of Energy, National Aeronautics and Space Administration, or the U.S. Navy., (Copyright © 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

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/m 3 -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/m 3 -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/m 3 -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.

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 ( 235 U) 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.

This article summarizes a Symposium on 'Radiation risks of the central nervous system' held virtually at the 67th Annual Meeting of the Radiation Research Society, 3-6 October 2021. Repeated low-dose radiation exposure over a certain period could lead to reduced neuronal proliferation, altered neurogenesis, neuroinflammation and various neurological complications, including psychological consequences, necessitating further research in these areas. Four speakers from radiation biology, genetics and epidemiology presented the latest data from their studies seeking insights into this important topic. This symposium highlighted new and important directions for further research on mental health disorders, neurodegenerative conditions and cognitive impairment. Future studies will examine risks of mental and behavioral disorders and neurodegenerative diseases following protracted radiation exposures to better understand risks of occupational exposures as well as provide insights into risks from exposures to galactic cosmic rays.

Background: Estimates of radiation risks following prolonged exposures at low doses and low-dose rates are uncertain. Medical radiation workers are a major component of the Million Person Study (MPS) of low-dose health effects. Annual personal dose equivalents, H P (10), for individual workers are available to facilitate dose-response analyses for lung cancer, leukemia, ischemic heart disease (IHD) and other causes of death., Materials and Methods: The Landauer, Inc. dosimetry database identified 109,019 medical and associated radiation workers first monitored 1965-1994. Vital status and cause of death were determined through 2016. Mean absorbed doses to red bone marrow (RBM), lung, heart, and other organs were estimated by adjusting the recorded H P (10) for each worker by scaling factors, accounting for exposure geometry, the energy of the incident photon radiation, sex of the worker and whether an apron was worn. There were 4 exposure scenarios: general radiology characterized by low-energy x-ray exposure with no lead apron use, interventional radiologists/cardiologists who wore aprons, nuclear medicine personnel and radiation oncologists exposed to high-energy photon radiation, and other workers. Standardized mortality ratio (SMR) analyses were performed. Cox proportional hazards models were used to estimate organ-specific radiation risks., Results: Overall, 11,433 deaths occurred (SMR 0.60; 95%CI 0.59,0.61), 126 from leukemia other than chronic lymphocytic leukemia (CLL), 850 from lung cancer, and 1654 from IHD. The mean duration of monitoring was 23.7 y. The excess relative rate (ERR) per 100 mGy was estimated as 0.10 (95% CI -0.34, 0.54) for leukemia other than CLL, 0.15 (0.02, 0.27) for lung cancer, and -0.10 (-0.27, 0.06) for IHD. The ERR for lung cancer was 0.16 (0.01, 0.32) among the 55,218 male workers and 0.09 (-0.19, 0.36) among the 53,801 female workers; a difference that was not statistically significant ( p -value = 0.23)., Conclusions: Medical radiation workers were at increased risk for lung cancer that was higher among men than women, although this difference was not statistically significant. In contrast, the study of Japanese atomic bomb survivors exposed briefly to radiation in 1945 found females to be nearly 3 times the radiation risk of lung cancer compared with males on a relative scale. For medical workers, there were no statistically significant radiation associations with leukemia excluding CLL, IHD or other specific causes of death. Combining these data with other cohorts within the MPS, such as nuclear power plant workers and nuclear submariners, will enable more precise estimates of radiation risks at relatively low cumulative doses.

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 -3 year -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: A substantial body of epidemiologic literature addresses risks associated with occupational radiation exposure but comparing results between studies is often difficult as different statistical models are commonly used. It is unclear whether different methods produce similar results for estimates of radiation risk when applied to the same data. The goal of this study was to compare the radiation risk estimates for leukemia other than chronic lymphocytic leukemia (non-CLL) and ischemic heart disease (IHD) produced by both Cox and Poisson regression models for time-dependent dose-response analyses of occupational exposure., Materials and Methods: For brevity, this methods paper presents the results from one cohort, the Nuclear Power Plant workers (NPP), though the evaluation considered five cohorts of varying size and exposure as part of the Million Worker Study. Cox Proportional Hazards models, with age as the underlying timescale for hazard, were conducted using three computer software programs: SAS, R, and Epicure. Doses lagged 2 years for non-CLL and 10 years for ischemic heart disease were treated as time-dependent exposures at the annual level and were examined both in categories and as a continuous term. Hazard ratios (HR) and 95% confidence intervals (CI) were reported for each model in SAS and R, while the Peanuts program of Epicure was utilized to produce Excess Relative Risk (ERR) estimates and 95% CI. All models were adjusted for gender and year of birth. Four piece-wise exponential Poisson models (log-linear regression for rate) were developed with varying cutpoints for age strata from very fine to broad categories using both R and the Amfit program in Epicure for ERR estimates., Results: Comparable estimates of risk (both RR and ERR) were observed from Cox and Poisson models, regardless of software utilized, as long as appropriately narrow categories of age were utilized to control the confounding of age in Poisson models. The ERR estimates produced in Epicure tended to agree very closely with the HR or RR estimates, and the statistical software program used had no impact to risk estimates for the same model., Conclusions: As computational power is no longer the burden today as it has been in the past, the results of this evaluation support the use of the Cox proportional hazards or the ungrouped Poisson approach to analyzing time-dependent dose-response relationships to ensure that maximum control over the confounding of age is achieved in studies of mortality for cohorts occupationally exposed to radiation.

Background: The aim of the Million Person Study of Low-Dose Health Effects (MPS) is to examine the level of radiation risk for chronic exposures received gradually over time and not acutely as was the case for the Japanese atomic bomb survivors. Nuclear power plant (NPP) workers comprise nearly 15 percent of the MPS. Leukemia, selected cancers, Parkinson's disease, ischemic heart disease (IHD) and other causes of death are evaluated., Methods and Material: The U.S. Nuclear Regulatory Commission's Radiation Exposure Information and Reporting System (REIRS) and the Landauer, Inc. dosimetry databases identified 135,193 NPP workers first monitored 1957-1984. Annual personal dose equivalents [ Hp(10) ] were available for each worker. Radiation records from all places of employment were sought. Vital status was determined through 2011. Mean absorbed doses to red bone marrow (RBM), esophagus, lung, colon, brain and heart were estimated by adjusting the recorded Hp(10) for each worker by scaling factors, accounting for exposure geometry and energy of the incident gamma radiation. Standardized mortality ratios (SMR) were calculated. Radiation risks were estimated using Cox proportional hazards models., Results: Nearly 50% of workers were employed for more than 20 years. The mean duration of follow-up was 30.2 y. Overall, 29,124 total deaths occurred, 296 from leukemia other than chronic lymphocytic leukemia (CLL), 3382 from lung cancer, 140 from Parkinson's disease and 5410 from IHD. The mean dose to RBM was 37.9 mGy (maximum 1.0 Gy; percent >100 mGy was 9.2%), 43.2 mGy to lung, 43.7 mGy to colon, 33.2 mGy to brain, and 43.9 mGy to heart. The SMRs (95% CI) were 1.06 (0.94; 1.19) for leukemia other than CLL, 1.10 (1.07; 1.14) for lung cancer, 0.90 (0.76; 1.06) for Parkinson's disease, and 0.80 (0.78; 0.82) for IHD. The excess relative risk (ERR) per 100 mGy for leukemia other than CLL was 0.15 (90% CI -0.001; 0.31). For all solid cancers the ERR per 100 mGy (95% CI) was 0.01 (-0.03; 0.05), for lung cancer -0.04 (-0.11; 0.02), for Parkinson's disease 0.24 (-0.02; 0.50), and for IHD -0.01 (-0.06; 0.04)., Conclusion: Prolonged exposure to radiation increased the risk of leukemia other than CLL among NPP workers. There was little evidence for a radiation association for all solid cancers, lung cancer or ischemic heart disease. Increased precision will be forthcoming as the different cohorts within the MPS are combined, such as industrial radiographers and medical radiation workers who were assembled and evaluated in like manner.

Background: During World War II (WWII), the Manhattan Engineering District established a secret laboratory in the mountains of northern New Mexico. The mission was to design, construct and test the first atomic weapon, nicknamed 'The Gadget' that was detonated at the TRINITY site in Alamogordo, NM. After WWII, nuclear weapons research continued, and the laboratory became the Los Alamos National Laboratory (LANL)., Materials and Methods: The mortality experience of 26,328 workers first employed between 1943 and 1980 at LANL was determined through 2017. Included were 6157 contract workers employed by the ZIA Company. Organ dose estimates for each worker considered all sources of exposure, notably photons, neutrons, tritium, 238 Pu and 239 Pu. Vital status determination included searches within the National Death Index, Social Security Administration and New Mexico State Mortality Files. Standardized Mortality Ratios (SMR) and Cox regression models were used in the analyses., Results: Most workers (55%) were hired before 1960, 38% had a college degree, 25% were female, 81% white, 13% Hispanic and 60% had died. Vital status was complete, with only 0.1% lost to follow-up. The mean dose to the lung for the 17,053 workers monitored for radiation was 28.6 weighted-mGy (maximum 16.8 weighted-Gy) assuming a Dose Weighting Factor of 20 for alpha particle dose to lung. The Excess Relative Risk (ERR) at 100 weighted-mGy was 0.01 (95%CI -0.02, 0.03; n  = 839) for lung cancer. The ERR at 100 mGy was -0.43 (95%CI -1.11, 0.24; n  = 160) for leukemia other than chronic lymphocytic leukemia (CLL), -0.06 (95%CI -0.16, 0.04; n  = 3043) for ischemic heart disease (IHD), and 0.29 (95%CI 0.02, 0.55; n  = 106) for esophageal cancer. Among the 6499 workers with measurable intakes of plutonium, an increase in bone cancer (SMR 2.44; 95%CI 0.98, 5.03; n  = 7) was related to dose. The SMR for berylliosis was significantly high, based on 4 deaths. SMRs for Hispanic workers were significantly high for cancers of the stomach and liver, cirrhosis of the liver, nonmalignant kidney disease and diabetes, but the excesses were not related to radiation dose., Conclusions: There was little evidence that radiation increased the risk of lung cancer or leukemia. Esophageal cancer was associated with radiation, and plutonium intakes were linked to an increase of bone cancer. IHD was not associated with radiation dose. More precise evaluations will await the pooled analysis of workers with similar exposures such as at Rocky Flats, Savannah River and Hanford.

Mallinckrodt Chemical Works was the earliest uranium processing facility in the Manhattan Project, beginning in 1942. Even then, concern existed about possible health effects resulting from exposure to radiation and pitchblende dust. This concern was well founded as the facility processed Belgian Congo pitchblende ore that was up to 60% pure uranium with high U content and up to 100 mg of radium per ton. Workers were exposed to external gamma radiation plus internal radiation from inhalation and ingestion of pitchblende dust (uranium, radium, and silica). Multiple sources of exposure were available for organ dose reconstruction to a degree unique for an epidemiologic study. Personal film badge measures available from 1945 captured external exposures. Additional external exposure included 15,518 occupational medical x-rays and 210 radiation exposure records from other facilities outside of Mallinckrodt employment. Organ dose calculations considered organ-specific coefficients that account for photon energy and job-specific orientation of workers to the radiation source during processing. Intakes of uranium and radium were based on 39,451 uranium urine bioassays and 2,341 breath radon measurements, and International Commission on Radiological Protection (ICRP) Publication 68 biokinetic models were used to estimate organ-specific radiation absorbed dose. Estimates of exposure to airborne radon and its short-lived progeny were based on radon measurements in work areas where radium-containing materials were handled or stored, together with estimated exposure times in these areas based on job titles. Dose estimates for radon and its short-lived progeny were based on models and methods recently recommended in ICRP Publication 137. This comprehensive dosimetric approach follows methods outlined by the National Council on Radiation Protection Scientific Committee 6-9 for the Million Worker Study. Annual doses were calculated for six organs: lung, brain, heart, kidney, colon and red bone marrow. Evaluation and adjustment for individual cumulative measures of pitchblende dust inhalation were made for lung and kidney diseases.

The purpose of this paper is to present an overview of ongoing work on the Million Worker Study (MWS), highlighting some of the key methods and progress so far as exemplified by the study of workers at the Mallinckrodt Chemical Works (MCW). The MWS began nearly 25 y ago and continues in a stepwise fashion, evaluating one study cohort at a time. It includes workers from U.S. Department of Energy (DOE) Manhattan Project facilities, U.S. Nuclear Regulatory Commission (NRC) regulated nuclear power plants, industrial radiographers, U.S. Department of Defense (DoD) nuclear weapons test participants, and physicians and technologists working with medical radiation. The purpose is to fill the major gap in radiation protection and science: What is the risk when exposure is received gradually over time rather than briefly as for the atomic bomb survivors? Studies published or planned in 2018 include leukemia (and dosimetry) among atomic veterans, leukemia among nuclear power plant workers, mortality among workers at the MCW, and a comprehensive National Council on Radiation Protection and Measurements (NCRP) Report on dosimetry for the MWS. MCW has a singular place in history: the 40 tons (T) of uranium oxide produced at MCW were used by Enrico Fermi on 2 December 1942 to produce the first manmade sustained and controlled nuclear reaction, and the atomic age was born. Seventy-six years later, the authors followed the over 2,500 MCW workers for mortality and reconstructed dose from six sources of exposure: external gamma rays from the radioactive elements in pitchblende; medical x rays from occupationally required chest examinations; intakes of pitchblende (uranium, radium, and silica) measured by urine samples; radon breath analyses and dust surveys overseen by Robley Evans and Merril Eisenbud; occupational exposures received before and after employment at MCW; and cumulative radon concentrations and lung dose from the decay of radium in the work environment. The unique exposure reconstructions allow for multiple evaluations, including estimates of silica dust. The study results are relevant today. For example, NASA is interested that radium, deposited in the brain, releases high-LET alpha particles - the only human analogue, though limited, for high energy, high-Z particles (galactic cosmic rays) traveling through space that might affect astronauts on Mars missions. Don't discount the past; it's the prologue to the future!

Workers engaged in the production of Portland cement may come into contact with potential occupational hazards, but existing epidemiological studies show wide variation in risk estimates for cancer incidence and mortality in relation to cement exposure. This report identified studies of cement workers and associations with cancer incidence and mortality in a systematic review and meta-analysis. A systematic review according to the PRISMA guidelines was conducted to identify studies of Portland cement workers and cancer outcomes. Meta-analyses were performed using random effects models for all cancers combined and for each cancer site with three or more reported measures of risk. A total of 26 studies were included in the review (14 occupational cohort studies and 12 case-control studies). Overall, the meta-relative risks did not provide convincing evidence for increased risks of any cancers in relation to cement exposure. Meta-SMR and 95% CIs were 0.94 (0.76 to 1.16) for six studies reporting all cancers combined, 0.93 (0.62 to 1.39) for seven studies reporting on lung cancer, 1.07 (0.72 to 1.59) for five studies reporting on stomach cancer, and 1.05 (0.79 to 1.40) for four studies reporting on colorectal cancer. Meta-relative risks for cancer incidence were similarly null for all sites with the exception of colorectal cancer which had a borderline statistically significant elevated risk (SIR=1.38, 95% CI 1.02 to 1.88). Overall, the meta-relative risks calculated across 26 published studies do not provide evidence of increased risks for cancer in relation to cement exposure., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Exposure to chlorpyrifos (CPF), an organophosphorus (OP) anticholinesterase insecticide, occurs typically in settings where multiple agents are present (e.g., agriculture) and quantitative dose measures may be absent (e.g., pesticide application). Such exposures allow few opportunities to study potential neurobehavioral effects of CPF alone. We studied the relationship between CPF exposure and behavioral function among CPF manufacturing workers, which allowed identification, measurement, and estimation of exposure and important non-exposure variables that potentially could affect study findings., Methods: A prospective longitudinal study design was used to compare neurobehavioral function over a one-year period among 53 CPF workers and 60 referent workers. Quantitative and qualitative measures were used, and potential confounders were identified and tested for possible inclusion in our statistical models. Neurobehavioral function was assessed by neuropsychological tests covering various behavioral domains that may be adversely affected by exposure to CPF in sufficient amount., Results: CPF workers had significantly greater CPF exposures during the study period than did referents at levels where physiologic effects on plasma butyrylcholinesterase (BuChE) activity were apparent and with higher 3,5,6-trichloro-2-pyridinol (TCPy/Cr) urinary excretion (p<0.0001) and lower average BuChE activity (p<0.01). No evidence for impaired neurobehavioral domains by either group of workers was observed at baseline, on repeat examination, or between examinations. CPF workers scored higher than referent workers on the verbal memory domain score (p=0.03) at baseline, but there were no significant changes in verbal memory over time and no significant group-by-time interactions., Conclusions: The study provides important information about CPF exposure in the workplace by not supporting our working hypothesis that CPF exposure associated with various aspects of the manufacturing process would be accompanied by adverse neurobehavioral effects detectable by quantitative neurobehavioral testing. Some aspects making this workplace site attractive for study and also present limitations for the generalization of results to other situations that might have exposures that vary widely between and within different facilities and locations. For example, these results might not apply to occupations such as applicators with higher exposure or to workers with low educational levels., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Polonium-210 is a naturally occurring radioactive element that decays by emitting an alpha particle. It is in the air we breathe and also a component of tobacco smoke. Polonium-210 is used as an anti-static device in printing presses and gained widespread notoriety in 2006 after the poisoning and subsequent death of a Russian citizen in London. More is known about the lethal effects of polonium-210 at high doses than about late effects from low doses. Cancer mortality was examined among 7,270 workers at the Mound nuclear facility near Dayton, OH where polonium-210 was used (1944-1972) in combination with beryllium as a source of neutrons for triggering nuclear weapons. Other exposures included external gamma radiation and to a lesser extent plutonium-238, tritium and neutrons. Vital status and cause of death was determined through 2009. Standardized mortality ratios (SMRs) were computed for comparisons with the general population. Lifetime occupational doses from all places of employment were sought and incorporated into the analysis. Over 200,000 urine samples were analyzed to estimate radiation doses to body organs from polonium and other internally deposited radionuclides. Cox proportional hazards models were used to evaluate dose-response relationships for specific organs and tissues. Vital status was determined for 98.7% of the workers of which 3,681 had died compared with 4,073.9 expected (SMR 0.90; 95% CI 0.88-0.93). The mean dose from external radiation was 26.1 mSv (maximum 939.1 mSv) and the mean lung dose from external and internal radiation combined was 100.1 mSv (maximum 17.5 Sv). Among the 4,977 radiation workers, all cancers taken together (SMR 0.86; 95% CI 0.79-0.93), lung cancer (SMR 0.85; 95% CI 0.74-0.98), and other types of cancer were not significantly elevated. Cox regression analysis revealed a significant positive dose-response trend for esophageal cancer [relative risk (RR) and 95% confidence interval at 100 mSv of 1.54 (1.15-2.07)] and a negative dose-response trend for liver cancer [RR (95% CI) at 100 mSv of 0.55 (0.23-1.32)]. For lung cancer the RR at 100 mSv was 1.00 (95% CI 0.97-1.04) and for all leukemias other than chronic lymphocytic leukemia (CLL) it was 1.04 (95% CI 0.63-1.71). There was no evidence that heart disease was associated with exposures [RR at 100 mSv of 1.06 (0.95-1.18)]. Assuming a relative biological effectiveness factor of either 10 or 20 for polonium and plutonium alpha particle emissions had little effect on the dose-response analyses. Polonium was the largest contributor to lung dose, and a relative risk of 1.04 for lung cancer at 100 mSv could be excluded with 95% confidence. A dose related increase in cancer of the esophagus was consistent with a radiation etiology but based on small numbers. A dose-related decrease in liver cancer suggests the presence of other modifying factors of risk and adds caution to interpretations. The absence of a detectable increase in total cancer deaths and lung cancer in particular associated with occupational exposures to polonium (mean lung dose 159.8 mSv), and to plutonium to a lesser extent (mean lung dose 13.7 mSv), is noteworthy but based on small numbers. Larger combined studies of U.S. workers are needed to clarify radiation risks following prolonged exposures and radionuclide intakes.

Updated analyses of mortality data are presented on 46,970 workers employed 1948-1999 at Rocketdyne (Atomics International). Overall, 5,801 workers were involved in radiation activities, including 2,232 who were monitored for intakes of radionuclides, and 41,169 workers were engaged in rocket testing or other non-radiation activities. The worker population is unique in that lifetime occupational doses from all places of employment were sought, updated and incorporated into the analyses. Further, radiation doses from intakes of 14 different radionuclides were calculated for 16 organs or tissues using biokinetic models of the International Commission on Radiation Protection (ICRP). Because only negligible exposures were received by the 247 workers monitored for radiation activities after 1999, the mean dose from external radiation remained essentially the same at 13.5 mSv (maximum 1 Sv) as reported previously, as did the mean lung dose from external and internal radiation combined at 19.0 mSv (maximum 3.6 Sv). An additional 9 years of follow-up, from December 31,1999 through 2008, increased the person-years of observation for the radiation workers by 21.7% to 196,674 (mean 33.9 years) and the number of cancer deaths by 50% to 684. Analyses included external comparisons with the general population and the computation of standardized mortality ratios (SMRs) and internal comparisons using proportional hazards models and the computation of relative risks (RRs). A low SMR for all causes of death (SMR 0.82; 95% CI 0.78-0.85) continued to indicate that the Rocketdyne radiation workers were healthier than the general population and were less likely to die. The SMRs for all cancers taken together (SMR 0.88; 95% CI 0.81-0.95), lung cancer (SMR 0.87; 95% CI 0.76-1.00) and leukemia other than chronic lymphocytic leukemia (CLL) (SMR 1.04; 95% 0.67-1.53) were not significantly elevated. Cox regression analyses revealed no significant dose-response trends for any cancer. For all cancers excluding leukemia, the RR at 100 mSv was estimated as 0.98 (95% CI 0.82-1.17), and for all leukemia other than CLL it was 1.06 (95% CI 0.50-2.23). Uranium was the primary radionuclide contributing to internal exposures, but no significant increases in lung and kidney disease were seen. The extended follow-up reinforces the findings in the previous study in failing to observe a detectable increase in cancer deaths associated with radiation, but strong conclusions still cannot be drawn because of small numbers and relatively low career doses. Larger combined studies of early workers in the United States using similar methodologies are warranted to refine and clarify radiation risks after protracted exposures.

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.

We performed nerve conduction studies (NCSs) on 113 chemical workers, many of whom had occupational exposure to the organophosphorus insecticide chlorpyrifos (O,O-diethyl-O-[3,5,6-trichloro-2-pyridyl]-phosphorothioate), to identify dose effects of subclinical neuropathy. In this masked longitudinal study, we estimated historic and interim chlorpyrifos exposures and measured excretion of 3,5,6 trichloro-2-pyridinol (TCP), a chlorpyrifos metabolite. TCP excretion among exposed workers suggested an estimated daily chlorpyrifos exposure averaging about 576-627 microg/day and indicated levels approximately 30% (range 0-250%) of the internal dose received by a typical subject exposed during a working day at the threshold limit value of 200 microg/m3. We modeled NCS results using linear mixed models with repeated measures. Although we found no consistent associations between interim chlorpyrifos exposure and NCS results, we identified several significant associations involving historic chlorpyrifos exposure. Most associations, however, reflected effects at low-exposure levels (< 20 mg/m3 x days) without further effects as exposure increased over a 10-fold range (20-220 mg/m3 x days). This suggested small differences among subjects with low or no chlorpyrifos exposure, rather than a dose-related deterioration among subjects with higher exposures. Two NCS results demonstrating apparent subclinical adverse dose effects showed significant but unexplained interaction with education level. The overall results provide little support for the hypothesis that chronic chlorpyrifos exposures at levels in the range associated with appreciable inhibition of B-esterases produce adverse dose effects on peripheral nerve electrophysiology suggestive of subclinical neuropathy.

Objective: The objective of this study was to evaluate potential health risks associated with testing rocket engines., Methods: A retrospective cohort mortality study was conducted of 8372 Rocketdyne workers employed 1948 to 1999 at the Santa Susana Field Laboratory (SSFL). Standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) were calculated for all workers, including those employed at specific test areas where particular fuels, solvents, and chemicals were used. Dose-response trends were evaluated using Cox proportional hazards models., Results: SMRs for all cancers were close to population expectations among SSFL workers overall (SMR = 0.89; CI = 0.82-0.96) and test stand mechanics in particular (n = 1651; SMR = 1.00; CI = 0.86-1.16), including those likely exposed to hydrazines (n = 315; SMR = 1.09; CI = 0.75-1.52) or trichloroethylene (TCE) (n = 1111; SMR = 1.00; CI = 0.83-1.19). Nonsignificant associations were seen between kidney cancer and TCE, lung cancer and hydrazines, and stomach cancer and years worked as a test stand mechanic. No trends over exposure categories were statistically significant., Conclusion: Work at the SSFL rocket engine test facility or as a test stand mechanic was not associated with a significant increase in cancer mortality overall or for any specific cancer.

A retrospective cohort mortality study was conducted of workers engaged in nuclear technology development and employed for at least 6 months at Rocketdyne (Atomics International) facilities in California, 1948-1999. Lifetime occupational doses were derived from company records and linkages with national dosimetry data sets. International Commission on Radiation Protection (ICRP) biokinetic models were used to estimate radiation doses to 16 organs or tissues after the intake of radionuclides. Standardized mortality ratios (SMRs) compared the observed numbers of deaths with those expected in the general population of California. Cox proportional hazards models were used to evaluate dose-response trends over categories of cumulative radiation dose, combining external and internal organ-specific doses. There were 5,801 radiation workers, including 2,232 monitored for radionuclide intakes. The mean dose from external radiation was 13.5 mSv (maximum 1 Sv); the mean lung dose from external and internal radiation combined was 19.0 mSv (maximum 3.6 Sv). Vital status was determined for 97.6% of the workers of whom 25.3% (n = 1,468) had died. The average period of observation was 27.9 years. All cancers taken together (SMR 0.93; 95% CI 0.84-1.02) and all leukemia excluding chronic lymphocytic leukemia (CLL) (SMR 1.21; 95% CI 0.69-1.97) were not significantly elevated. No SMR was significantly increased for any cancer or for any other cause of death. The Cox regression analyses revealed no significant dose-response trends for any cancer. For all cancers excluding leukemia, the RR at 100 mSv was estimated as 1.00 (95% CI 0.81-1.24), and for all leukemia excluding CLL it was 1.34 (95% CI 0.73-2.45). The nonsignificant increase in leukemia (excluding CLL) was in accord with expectation from other radiation studies, but a similar nonsignificant increase in CLL (a malignancy not found to be associated with radiation) tempers a causal interpretation. Radiation exposure has not caused a detectable increase in cancer deaths in this population, but results are limited by small numbers and relatively low career doses.

Incomplete radiation exposure histories, inadequate treatment of internally deposited radionuclides, and failure to account for neutron exposures can be important uncertainties in epidemiologic studies of radiation workers. Organ-specific doses from lifetime occupational exposures and radionuclide intakes were estimated for an epidemiologic study of 5,801 Rocketdyne/Atomics International (AI) radiation workers engaged in nuclear technologies between 1948 and 1999. The entire workforce of 46,970 Rocketdyne/AI employees was identified from 35,042 Kardex work histories cards, 26,136 electronic personnel listings, and 14,189 radiation folders containing individual exposure histories. To obtain prior and subsequent occupational exposure information, the roster of all workers was matched against nationwide dosimetry files from the Department of Energy, the Nuclear Regulatory Commission, the Landauer dosimetry company, the U.S. Army, and the U.S. Air Force. Dosimetry files of other worker studies were also accessed. Computation of organ doses from radionuclide intakes was complicated by the diversity of bioassay data collected over a 40-y period (urine and fecal samples, lung counts, whole-body counts, nasal smears, and wound and incident reports) and the variety of radionuclides with documented intake including isotopes of uranium, plutonium, americium, calcium, cesium, cerium, zirconium, thorium, polonium, promethium, iodine, zinc, strontium, and hydrogen (tritium). Over 30,000 individual bioassay measurements, recorded on 11 different bioassay forms, were abstracted. The bioassay data were evaluated using ICRP biokinetic models recommended in current or upcoming ICRP documents (modified for one inhaled material to reflect site-specific information) to estimate annual doses for 16 organs or tissues taking into account time of exposure, type of radionuclide, and excretion patterns. Detailed internal exposure scenarios were developed and annual internal doses were derived on a case-by-case basis for workers with committed equivalent doses indicated by screening criteria to be greater than 10 mSv to the organ with the highest internal dose. Overall, 5,801 workers were monitored for radiation at Rocketdyne/AI: 5,743 for external exposure and 2,232 for internal intakes of radionuclides; 41,169 workers were not monitored for radiation. The mean cumulative external dose based on Rocketdyne/AI records alone was 10.0 mSv, and the dose distribution was highly skewed with most workers experiencing low cumulative doses and only a few with high doses (maximum 500 mSv). Only 45 workers received greater than 200 mSv while employed at Rocketdyne/AI. However, nearly 32% (or 1,833) of the Rocketdyne/AI workers had been monitored for radiation at other nuclear facilities and incorporation of these doses increased the mean dose to 13.5 mSv (maximum 1,005 mSv) and the number of workers with >200 mSv to 69. For a small number of workers (n=292), lung doses from internal radionuclide intakes were relatively high (mean 106 mSv; maximum 3,560 mSv) and increased the overall population mean dose to 19.0 mSv and the number of workers with lung dose>200 mSv to 109. Nearly 10% of the radiation workers (584) were monitored for neutron exposures (mean 1.2 mSv) at Rocketdyne/AI, and another 2% were monitored for neutron exposures elsewhere. Interestingly, 1,477 workers not monitored for radiation at Rocketdyne/AI (3.6%) were found to have worn dosimeters at other nuclear facilities (mean external dose of 2.6 mSv, maximum 188 mSv). Without considering all sources of occupational exposure, an incorrect characterization of worker exposure would have occurred with the potential to bias epidemiologic results. For these pioneering workers in the nuclear industry, 26.5% of their total occupational dose (collective dose) was received at other facilities both prior to and after employment at Rocketdyne/AI. In addition, a small number of workers monitored for internal radionuclides contributed disproportionately to the number of workers with high lung doses. Although nearly 12% of radiation workers had been monitored for neutron exposures during their career, the cumulative dose levels were small in comparison with other external and internal exposure. Risk estimates based on nuclear worker data must be interpreted cautiously if internally deposited radionuclides and occupational doses received elsewhere are not considered.

Objective: To assess potential health risks associated with work in a large motion picture film-processing facility., Methods: A retrospective cohort mortality study was conducted during 1960-2000 among 2646 film workers. Job family categories, created from detailed employee work history information, were used to evaluate chemical exposure patterns., Results: Overall mortality was as expected (standardized mortality ratio [SMR] = 1.1; 95% confidence interval [CI] = 1.0-1.2). Statistically significant associations were found for suicides (SMR = 2.0; 95% CI = 1.2-3.0) among the hourly workers and AIDS (SMR = 5.3; 95% CI = 1.7-12.3) among the administrative workers. Film developers had increases of respiratory cancer (SMR = 1.9; 95% CI = 1.1-3.0) and suicides (SMR = 2.4; 95% CI = 1.0-4.7), whereas film assemblers had an increase in suicides (SMR = 2.4; 95% CI = 1.2-4.4) only., Conclusions: Excess deaths resulting from suicides and AIDS among the workforce suggest that nonoccupational influences may be involved in the mortality of this cohort and warrant further investigations.