ObjectivesRadon is a ubiquitous occupational and environmental lung carcinogen. We aim to quantify the association between radon progeny and lung cancer mortality in the largest and most up-to-date ...pooled study of uranium miners.MethodsThe pooled uranium miners analysis combines 7 cohorts of male uranium miners with 7754 lung cancer deaths and 4.3 million person-years of follow-up. Vital status and lung cancer deaths were ascertained between 1946 and 2014. The association between cumulative radon exposure in working level months (WLM) and lung cancer was modelled as the excess relative rate (ERR) per 100 WLM using Poisson regression; variation in the association by temporal and exposure factors was examined. We also examined analyses restricted to miners first hired before 1960 and with <100 WLM cumulative exposure.ResultsIn a model that allows for variation by attained age, time since exposure and annual exposure rate, the ERR/100 WLM was 4.68 (95% CI 2.88 to 6.96) among miners who were less than 55 years of age and were exposed in the prior 5 to <15 years at annual exposure rates of <0.5 WL. This association decreased with older attained age, longer time since exposure and higher annual exposure rate. In analyses restricted to men first hired before 1960, we observed similar patterns of association but a slightly lower estimate of the ERR/100 WLM.ConclusionsThis new large, pooled study confirms and supports a linear exposure–response relationship between cumulative radon exposure and lung cancer mortality which is jointly modified by temporal and exposure factors.
The results of early animal studies of engineered nanomaterials (ENMs) and air pollution epidemiology suggest that it is important to assess the health of ENM workers. Initial epidemiological studies ...of workers’ exposure to ENMs (<100 nm) are reviewed and characterized for their study designs, findings, and limitations. Of the 15 studies, 11 were cross-sectional, 4 were longitudinal (1 was both cross-sectional and longitudinal in design), and 1 was a descriptive pilot study. Generally, the studies used biologic markers as the dependent variables. All 11 cross-sectional studies showed a positive relationship between various biomarkers and ENM exposures. Three of the four longitudinal studies showed a negative relationship; the fourth showed positive findings after a 1-year follow-up. Each study considered exposure to ENMs as the independent variable. Exposure was assessed by mass concentration in 10 studies and by particle count in six studies. Six of them assessed both mass and particle concentrations. Some of the studies had limited exposure data because of inadequate exposure assessment. Generally, exposure levels were not very high in comparison to those in human inhalation chamber studies, but there were some exceptions. Most studies involved a small sample size, from 2 to 258 exposed workers. These studies represent the first wave of epidemiological studies of ENM workers. They are limited by small numbers of participants, inconsistent (and in some cases inadequate) exposure assessments, generally low exposures, and short intervals between exposure and effect. Still, these studies are a foundation for future work; they provide insight into where ENM workers are experiencing potentially adverse effects that might be related to ENM exposures.
ObjectivesAnimal bioassays have demonstrated convincing evidence of the potential carcinogenicity to humans of titanium dioxide (TiO2), but limitations in cohort studies have been identified, among ...which is the healthy worker survivor effect (HWSE). We aimed to address this bias in a pooled study of four cohorts of TiO2 workers.MethodsWe reanalysed data on respirable TiO2 dust exposure and lung cancer mortality among 7341 male workers employed in TiO2 production in Finland, France, UK and Italy using the parametric g-formula, considering three hypothetical interventions: setting annual exposures at 2.4 (U.S. occupational exposure limit), 0.3 (German limit) and 0 mg/m3 for 25 and 35 years.ResultsThe HWSE was evidenced. Taking this into account, we observed a positive association between lagged cumulative exposure to TiO2 and lung cancer mortality. The estimated number of lung cancer deaths at each age group decreased across increasingly stringent intervention levels. At age 70 years, the estimated number of lung cancer deaths expected in the cohort after 35-year exposure was 293 for exposure set at 2.4 mg/m3, 235 for exposure set at 0.3 mg/m3, and 211 for exposure set at 0 mg/m3.ConclusionThis analysis shows that HWSE can hide an exposure–response relationship. It also shows that TiO2 epidemiological data could demonstrate an exposure–effects relationship if analysed appropriately. More epidemiological studies and similar reanalyses of existing cohort studies are warranted to corroborate the human carcinogenicity of TiO2. This human evidence, when combined with the animal evidence, strengthens the overall evidence of carcinogenicity of TiO2.
The Life Span Study (LSS) of Japanese atomic bomb survivors has served as the primary basis for estimates of radiation-related disease risks that inform radiation protection standards. The long-term ...follow-up of radiation-monitored nuclear workers provides estimates of radiation-cancer associations that complement findings from the LSS. Here, a comparison of radiation-cancer mortality risk estimates derived from the LSS and INWORKS, a large international nuclear worker study, is presented. Restrictions were made, so that the two study populations were similar with respect to ages and periods of exposure, leading to selection of 45,625 A-bomb survivors and 259,350 nuclear workers. For solid cancer, excess relative rates (ERR) per gray (Gy) were 0.28 (90% CI 0.18; 0.38) in the LSS, and 0.29 (90% CI 0.07; 0.53) in INWORKS. A joint analysis of the data allowed for a formal assessment of heterogeneity of the ERR per Gy across the two studies (
P
= 0.909), with minimal evidence of curvature or of a modifying effect of attained age, age at exposure, or sex in either study. There was evidence in both cohorts of modification of the excess absolute risk (EAR) of solid cancer by attained age, with a trend of increasing EAR per Gy with attained age. For leukemia, under a simple linear model, the ERR per Gy was 2.75 (90% CI 1.73; 4.21) in the LSS and 3.15 (90% CI 1.12; 5.72) in INWORKS, with evidence of curvature in the association across the range of dose observed in the LSS but not in INWORKS; the EAR per Gy was 3.54 (90% CI 2.30; 5.05) in the LSS and 2.03 (90% CI 0.36; 4.07) in INWORKS. These findings from different study populations may help understanding of radiation risks, with INWORKS contributing information derived from cohorts of workers with protracted low dose-rate exposures.
Workers' smoking histories are not measured in many occupational cohort studies. Here we discuss the use of negative control outcomes to detect and adjust for confounding in analyses that lack ...information on smoking. We clarify the assumptions necessary to detect confounding by smoking and the additional assumptions necessary to indirectly adjust for such bias. We illustrate these methods using data from 2 studies of radiation and lung cancer: the Colorado Plateau cohort study (1950-2005) of underground uranium miners (in which smoking was measured) and a French cohort study (1950-2004) of nuclear industry workers (in which smoking was unmeasured). A cause-specific relative hazards model is proposed for estimation of indirectly adjusted associations. Among the miners, the proposed method suggests no confounding by smoking of the association between radon and lung cancer--a conclusion supported by adjustment for measured smoking. Among the nuclear workers, the proposed method suggests substantial confounding by smoking of the association between radiation and lung cancer. Indirect adjustment for confounding by smoking resulted in an 18% decrease in the adjusted estimated hazard ratio, yet this cannot be verified because smoking was unmeasured. Assumptions underlying this method are described, and a cause-specific proportional hazards model that allows easy implementation using standard software is presented.
To evaluate the effect of protracted low dose, low dose rate exposure to ionising radiation on the risk of cancer.
Multinational cohort study.
Cohorts of workers in the nuclear industry in France, ...the UK, and the US included in a major update to the International Nuclear Workers Study (INWORKS).
309 932 workers with individual monitoring data for external exposure to ionising radiation and a total follow-up of 10.7 million person years.
Estimates of excess relative rate per gray (Gy) of radiation dose for mortality from cancer.
The study included 103 553 deaths, of which 28 089 were due to solid cancers. The estimated rate of mortality due to solid cancer increased with cumulative dose by 52% (90% confidence interval 27% to 77%) per Gy, lagged by 10 years. Restricting the analysis to the low cumulative dose range (0-100 mGy) approximately doubled the estimate of association (and increased the width of its confidence interval), as did restricting the analysis to workers hired in the more recent years of operations when estimates of occupational external penetrating radiation dose were recorded more accurately. Exclusion of deaths from lung cancer and pleural cancer had a modest effect on the estimated magnitude of association, providing indirect evidence that the association was not substantially confounded by smoking or occupational exposure to asbestos.
This major update to INWORKS provides a direct estimate of the association between protracted low dose exposure to ionising radiation and solid cancer mortality based on some of the world's most informative cohorts of radiation workers. The summary estimate of excess relative rate solid cancer mortality per Gy is larger than estimates currently informing radiation protection, and some evidence suggests a steeper slope for the dose-response association in the low dose range than over the full dose range. These results can help to strengthen radiation protection, especially for low dose exposures that are of primary interest in contemporary medical, occupational, and environmental settings.
Carbon nanotubes and nanofibers (CNT/F) have known toxicity but simultaneous comparative studies of the broad material class, especially those with a larger diameter, with computational analyses ...linking toxicity to their fundamental material characteristics was lacking. It was unclear if all CNT/F confer similar toxicity, in particular, genotoxicity. Nine CNT/F (MW #1-7 and CNF #1-2), commonly found in exposure assessment studies of U.S. facilities, were evaluated with reported diameters ranging from 6 to 150 nm. All materials were extensively characterized to include distributions of physical dimensions and prevalence of bundled agglomerates. Human bronchial epithelial cells were exposed to the nine CNT/F (0-24 μg/ml) to determine cell viability, inflammation, cellular oxidative stress, micronuclei formation, and DNA double-strand breakage. Computational modeling was used to understand various permutations of physicochemical characteristics and toxicity outcomes.
Analyses of the CNT/F physicochemical characteristics illustrate that using detailed distributions of physical dimensions provided a more consistent grouping of CNT/F compared to using particle dimension means alone. In fact, analysis of binning of nominal tube physical dimensions alone produced a similar grouping as all characterization parameters together. All materials induced epithelial cell toxicity and micronuclei formation within the dose range tested. Cellular oxidative stress, DNA double strand breaks, and micronuclei formation consistently clustered together and with larger physical CNT/F dimensions and agglomerate characteristics but were distinct from inflammatory protein changes. Larger nominal tube diameters, greater lengths, and bundled agglomerate characteristics were associated with greater severity of effect. The portion of tubes with greater nominal length and larger diameters within a sample was not the majority in number, meaning a smaller percentage of tubes with these characteristics was sufficient to increase toxicity. Many of the traditional physicochemical characteristics including surface area, density, impurities, and dustiness did not cluster with the toxicity outcomes.
Distributions of physical dimensions provided more consistent grouping of CNT/F with respect to toxicity outcomes compared to means only. All CNT/F induced some level of genotoxicity in human epithelial cells. The severity of toxicity was dependent on the sample containing a proportion of tubes with greater nominal lengths and diameters.
INWORKS is a multinational cohort study, gathering 308 297 workers in the nuclear industry in France, the United Kingdom and the United States of America, with detailed individual monitoring data for ...external exposure to ionising radiation. Over a mean duration of follow-up of 27 y, the number of observed deaths was 66 632, including 17 957 deaths due to solid cancers, 1791 deaths due to haematological cancers and 27 848 deaths due to cardiovascular diseases. Mean individual cumulative external dose over the period 1945-2005 was 25 mSv. Analyses demonstrated a significant association between red bone marrow dose and the risk of leukaemia (excluding chronic lymphocytic leukaemia) and between colon dose and the risk of solid cancers. INWORKS assembled some of the strongest evidence to strengthen the scientific basis for the protection of adults from low dose, low-dose rate, exposures to ionising radiation.
In June, 2022, 25 scientists from eight countries met at the International Agency for Research on Cancer (IARC) in Lyon, France, to finalise their evaluation of the carcinogenicity of occupational ...exposure as a firefighter. Firefighters can be exposed to combustion products from fires (eg, polycyclic aromatic hydrocarbons PAHs and particulates), building materials (eg, asbestos), chemicals in firefighting foams (eg, perfluorinated and polyfluorinated substances PFAS), flame retardants, diesel exhaust, and other hazards (eg, night shift work and ultraviolet or other radiation). Dermal absorption of chemicals can occur even in firefighters wearing PPE due to limitations of its design, fit, maintenance, or decontamination. Since the previous classification of firefighting (as “possibly carcinogenic to humans,” Group 2B) by the IARC Monographs in 2007,2 many new studies have investigated the association between occupational exposure as a firefighter and cancer risk in humans. Airway and systemic inflammatory markers, such as IL-6 and IL-8, were associated with firefighting-related exposures. ...declines in lung function associated with changes in inflammatory markers and exposure-associated bronchial hyperreactivity were reported in firefighters.
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