Health Hazards for Uranium Mine and Mill Workers - Science Issues

(last updated 1 Feb 2024)

> See also:

• Uranium Mine and Mill Workers - Current Issues
• Radiation Exposure for Uranium Industry Workers
• Health Hazards for Nuclear Fuel Industry Workers - Science Issues
• Uranium Miner Health Risk Calculator
• Uranium Radiation Properties · Uranium Toxicity

Pooled study narrows down estimates for lifetime excess absolute risk from radon inhalation for uranium miners

Former Wismut uranium miners face increased lung cancer risk even 20-30 years after closure of the mines (Germany)

"[...] Notably, 20–30 years after closure of the Wismut mines in 1990, the estimated fraction of lung cancer deaths attributable to occupational radon exposure is still 26% in the full Wismut cohort and 19% in the 1960+ sub-cohort, respectively. This demonstrates the need for radiation protection against radon. [...]
The updated Wismut cohort study shows an increased lung cancer risk by radon for former miners even 20 to 30 years after the mines were closed and occupational radon exposures ended. The estimated lifetime excess absolute risk (LEAR per WLM) to die from lung cancer per unit of cumulative radon exposure in WLM varies between 3 and 7 × 10^–4 depending on model and (sub-) cohort, i.e. among 100 people with a cumulative occupational radon exposure of 100 WLM between 3 and 7 additional (excess) lung cancer deaths would occur due to this exposure during lifetime."

M. Kreuzer, V. Deffner, M. Sommer, et al.: Updated risk models for lung cancer due to radon exposure in the German Wismut cohort of uranium miners, 1946–2018 , in: Radiation and Environmental Biophysics, published online 11 Sep 2023

Pooled study confirms linear exposure-response relationship between cumulative radon exposure and lung cancer mortality among uranium miners

Study confirms lung cancer mortality for uranium miners employed in 1960 or later

"BACKGROUND: Despite reductions in exposure for workers and the general public, radon remains a leading cause of lung cancer. Prior studies of underground miners depended heavily upon information on deaths among miners employed in the early years of mine operations when exposures were high and tended to be poorly estimated.
OBJECTIVES: To strengthen the basis for radiation protection, we report on the follow-up of workers employed in the later periods of mine operations for hom we have more accurate exposure information and for whom exposures tended to be accrued at intensities that are more comparable to contemporary settings.
METHODS: We conducted a pooled analysis of cohort studies of lung cancer mortality among 57,873 male uranium miners in Canada, Czech Republic, France, Germany, and the United States, who were first employed in 1960 or later (thereby excluding miners employed during the periods of highest exposure and focusing on miners who tend to have higher quality assessments of radon progeny exposures). We derived estimates of excess relative rate per 100 working level months (ERR/100 WLM) for mortality from lung cancer.
RESULTS: The analysis included 1.9 million person-years of observation and 1,217 deaths due to lung cancer. The relative rate of lung cancer increased in a linear fashion with cumulative exposure to radon progeny (ERR/100 WLM = 1.33; 95% CI: 0.89, 1.88). The association was modified by attained age, age at exposure,and annual exposure rate; for attained ages <55y, the ERR/100 WLM was 8.38 (95% CI: 3.30, 18.99) among miners who were exposed at ≥35 years of age and at annual exposure rates of <0.5 working levels. This association decreased with older attained ages, younger ages at exposure, and higher exposure rates.
DISCUSSION: Estimates of association between radon progeny exposure and lung cancer mortality among relatively contemporary miners are coherent with estimates used to inform current protection guidelines. https://doi.org/10.1289/EHP10669"

Study findings suggest that uranium miners may be at higher risk for Cardiovascular diseases, based on their molecular biomarkers

"Abstract: The United States has a rich history of mining including uranium (U)-mining, coal mining, and other metal mining. Cardiovascular diseases (CVD) are largely understudied in miners and recent literature suggests that when compared to non-U miners, U-miners are more likely to report CVD. However, the molecular basis for this phenomenon is currently unknown.
In this pilot study, a New Mexico (NM)-based occupational cohort of current and former miners (n = 44) were recruited via a mobile screening clinic for miners. Serum- and endothelial-based endpoints were used to assess circulating inflammatory potential relevant to CVD. Non-U miners reported significantly fewer pack years of smoking than U-miners.
Circulating biomarkers of interest revealed that U-miners had significantly greater serum amyloid A (SAA), soluble intercellular adhesion molecule 1 (ICAM-1, ng/mL), soluble vascular cell adhesion molecule 1 (VCAM-1, ng/mL), and VCAM-1 mRNA expression, as determined by the serum cumulative inflammatory potential (SCIP) assay, an endothelial-based assay. Even after adjusting for various covariates, including age, multivariable analysis determined that U-miners had significantly upregulated VCAM-1 mRNA.
In conclusion, VCAM-1 may be an important biomarker and possible contributor of CVD in U-miners. Further research to explore this mechanism may be warranted."

Study finds positive association between cumulative radon exposure and cancers other than lung cancer among former uranium miners in the Příbram region of Czech Republic

"OBJECTIVES: Radon is carcinogenic, but more studies are needed to understand relationships with lung cancer and extrathoracic cancers at low exposures. There are few studies evaluating associations with cancer incidence or assessing the modifying effects of smoking.
METHODS: We conducted a case-cohort study with 16 434 underground uranium miners in the Czech Republic with cancer incidence follow-up 1977-1996. Associations between radon exposure and lung cancer, and extrathoracic cancer, were estimated with linear excess relative rate (ERR) models. We examined potential modifying effects of smoking, time since exposure and exposure rate.
RESULTS: Under a simple ERR model, assuming a 5-year exposure lag, the estimated ERR of lung cancer per 100 working level months (WLM) was 0.54 (95% CI 0.33 to 0.83) and the estimated ERR of extrathoracic cancer per 100 WLM was 0.07 (95% CI -0.17 to 0.72). Most lung cancer cases were observed among smokers (82%), and the estimated ERR of lung cancer per 100 WLM was larger among smokers (ERR/100 WLM=1.35; 95% CI 0.84 to 2.15) than among never smokers (ERR/100 WLM=0.12; 95% CI -0.05 to 0.49). Among smokers, the estimated ERR of lung cancer per 100 WLM decreased with time since exposure from 3.07 (95% CI -0.04 to 10.32) in the period 5-14 years after exposure to 1.05 (95% CI 0.49 to 1.87) in the period 25+ years after exposure.
CONCLUSIONS: We observed positive associations between cumulative radon exposure and lung cancer, consistent with prior studies. We observed a positive association between cumulative radon exposure and extrathoracic cancers, although the estimates were small. There was evidence that the association between radon and lung cancer was modified by smoking in a multiplicative or super-multiplicative fashion."

Study confirms radon-lung cancer association for former uranium miners in the Příbram region of Czech Republic, suggests radon also associated with other types of cancer mortality

"BACKGROUND: This study aims to estimate the association between radon and site-specific cancer mortality among a large contemporary cohort of male uranium miners.
METHODS: Annual occupational radon exposure was estimated based on a worker's duration of underground mining in a year and estimates of potential alpha energy of radon progeny in their location of work. Cancer mortality over the period 1977-1992 was ascertained for a cohort of 16434 male underground uranium miners employed in the Czech Republic between 1946 and 1992. Poisson regression was used to estimate relationships between cumulative radiation exposure (in working level months [WLM]) and site-specific cancer mortality.
RESULTS: Radon is positively associated with lung cancer mortality (excess relative rate [ERR] per 100 WLM = 0.2; 95% confidence interval [CI]: 0.10, 0.37). The best fit of the dose-response relationship between radon and lung cancer mortality was linear and estimates of radon-lung cancer associations varied by windows of time-since-exposure. Positive associations between radon and several types of cancer other than lung cancer were identified, notably chronic lymphocytic leukemia (CLL) (ERR/100 WLM = 0.24; 95% CI: [not determined [ND], 5.10]) and extrathoracic cancer (ERR/100 WLM = 0.12; 95% CI: [ND, 0.69]). We observed no associations between radon and stomach cancer, nor between radon and several hematopoietic cancer subtypes.
CONCLUSIONS: This study confirms the established radon-lung cancer association and suggests that radon may also be associated with other types of cancer mortality. Further investigations of extrathoracic and CLL cancer, with the aim of obtaining more precise estimates, are warranted to understand associations between radon and cancers other than lung."

Lung cancer risk for uranium miners confirmed even for low radon exposures

"It is well established that high radon exposures increase the risk of lung cancer mortality. The effects of low occupational exposures and the factors that confound and modify this risk are not clear and are needed to inform current radiation protection of miners. The risk of lung cancer mortality at low radon exposures (< 100 working-level months) was assessed in the joint cohort analysis of Czech, French, and Canadian uranium miners, employed in 1953 or later. Statistical analysis was based on linear Poisson regression modeling with grouped cohort survival data. Two sensitivity analyses were used to assess potential confounding from tobacco smoking. A statistically significant linear relationship between radon exposure and lung cancer mortality was found. The excess relative risk per working-level month was 0.022 (95% confidence intervals: 0.013-0.034), based on 408 lung cancer deaths and 394,236 person-years of risk. Time since exposure was a statistically significant modifier; risk decreased with increasing time since exposure. A tendency for a decrease in risk with increasing attained age was observed, but this was not statistically significant. Exposure rate was not found to be a modifier of the excess relative risk. The potential confounding effect of tobacco smoking was estimated to be small and did not substantially change the radon-lung cancer mortality risk estimates. This joint cohort analysis provides strong evidence for an increased risk of lung cancer mortality from low occupational radon exposures. The results suggest that radiation protection measures continue to be important among current uranium miners." [emphasis added]

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Greater odds for Angina in uranium miners than non-uranium miners in New Mexico

"RESULTS: Of the 7,215 eligible miners, most were men (96.3%). Uranium miners (n = 3,151, 43.7%) were older and diabetic, but less likely to currently smoke or use snuff (p </= 0.001 for all). After adjustment for covariates, uranium miners were more likely to report angina (O.R. 1.51, 95% C.I. 1.23, 1.85) than non-uranium miners.
CONCLUSIONS: Our data suggest that along with screening for pulmonary diseases, uranium industry workers should be screened for cardiovascular diseases."

Folluw-up of Ontario uranium miners' study suggests no increased risk of cancers other than lung cancer from relatively low cumulative exposure to radon

"OBJECTIVES: The study objectives were to extend the follow-up of the Ontario uranium miners cohort, one of the largest cohorts of uranium miners with low cumulative exposures, to examine the relationship between radon exposure and lung cancer mortality and, for the first time incidence, and address gaps in the literature, including dose-response relationship between radon exposure and other cancer sites, and non-cancer mortality. [...]
RESULTS: The cohort consisted of 28 546 male miners with a mean cumulative radon exposure of 21.0 working level months (WLM). An increased risk of lung cancer and a dose-response relationship was observed with cumulative radon exposure. Miners exposed to >100 WLM demonstrated a twofold increase in the risk of lung cancer incidence (RR=1.89, CI 1.43 to 2.50) compared with the non-exposed group, and a linear ERR of 0.64/100 WLM (CI 0.43 to 0.85), with similar results observed for mortality. No association was observed for other cancer sites (stomach, leukaemia, kidney and extrathoracic airways) or non-cancer sites (cardiovascular diseases) with increasing cumulative exposure to radon.
CONCLUSIONS: These findings suggest no increased risk of cancer sites other than lung or non-cancer mortality from relatively low cumulative exposure to radon."

International cohort study finds association between protracted low-dose radiation exposure and leukemia among nuclear workers

Cameco study claims solubility type classification of yellow cake from in situ leaching is 100% "fast"

"6.0 CONCLUSION
A simulated lung fluid experiment was performed to determine the solubility characteristics and dosimetric implications of the uranium products produced at both the Crow Butte and Smith Ranch - Highland Operations. The experimental data was assessed using methodologies described in ICRP 30 and in ICRP 66 / 71. The results show that using the earlier classifications (ICRP 30) that the material produced are primarily type D with a very small portion being a type W. Using the most recent classification methods (ICRP 71), all materials can be considered type F. More importantly, the experiment provided the solubility parameters that can be used to represent that actual dose and toxicity risk of our materials.
The dosimetry implications are that using the ICRP 30 classification, and weighting by the percentage of each class of material present, the annual limit on intake (ALI) and derived air concentrations (DAC) drop slightly from the default value of 5.0E-10 for Natural Uranium."

> Download Cameco Resources In-Situ Recovery Process-Specific Yellowcake Solubility Characteristics, March 14, 2011 (ADAMS Acc. No. ML110760153) [this is a text describing the report "Solubility of Radionuclides in Simulated Lung Fluid, Part 3 ISR and RLO Samples, October 2009" that was withheld from public disclosure]
> Download Cameco Crow Butte Lung Study Clarification, April 4, 2011 (ADAMS Acc. No. ML111020132)
> Download Cameco Crow Butte Lung Study Clarification, Sep. 9, 2011 (ADAMS Acc. No. ML11257A104)
> Download Solubility of Radionuclide in Simulated Lung Fluid , by G. Tairova, M. Boucher, K. Toews, et al., in: Uranium 2010, Proceedings of the 3rd International Conference on Uranium, in Saskatoon, Saskatchewan, Canada (ADAMS Acc. No. ML102640195)

In a more recent submission in connection with the license renewal for Smith Ranch, Cameco's conclusion on the solubility characteristics of the Smith Ranch - Highland yellowcake product reads like this:

Cameco has completed a solubility study to analyze the solubility characteristics of the Smith Ranch - Highland yellowcake product. This study showed that the yellowcake produced at Smith Ranch - Highland was primarily of solubility type D with a relatively low type W component. The resulting ALI and DAC values are the same as the default type D material at 1 µCi and 5E-10 µCi/ml. As stated in the introduction, this analysis of the data incorporates the most recent comments from the NRC and Cameco and supersedes all previous submissions in this area.

Appendix I - Revised April 2015, Smith Ranch Analysis of Day, Week, and Year Classification - Smith Ranch Radionuclide Mixture Assessment

Study finds excess chromosomal aberrations in Kazakh uranium mine/mill workers

Association of genetic polymorphism in GSTM1 and GSTT1 with the frequency of chromosomal aberrations in the uranium workers [in Russian], by Z. Zh. Vasileva, R. I. Bersimbaev, B. O. Bekmanov, I. E. Vorobtsova, in: Radiatsionnaia biologiia, radioecologiia , Vol. 50 (2010), No. 2 (March-April), p.148-152

Study finds association between cerebrovascular diseases mortality and cumulative radon exposure in French uranium miner cohort

"[...] METHODS: The cohort included men employed as uranium miners for >/=1 year between 1946-1990. We obtained vital status and cause of death from national registers and reconstructed radon exposure for each year. Exposure--risk relations were estimated with a linear excess relative risk (ERR) model using a 5-year lag time.
RESULTS: The cohort comprised 5086 miners, followed up for a mean duration of 30.1 years. The average cumulative exposure of the radon-exposed miners was 36.6 working level months (WLM). A total of 1411 deaths were observed, including 319 deaths due to CSD. No excess risk was found for this overall cause of death. A significant positive trend was observed between deaths from cerebrovascular diseases (CeVD) and cumulative radon exposure, together with a significant ERR per 100 WLM [ERR per 100 WLM 0.49, 95% confidence interval (95% CI) 0.07-1.23)]. Hard physical activity was identified as a potential modifying factor of the exposure-risk relation.
CONCLUSIONS: Our results suggest, for the first time in a cohort of uranium miners, an association between CeVD mortality and cumulative radon exposure. Due to a lack of data, which limited our ability to assess possible confounding by cardiovascular risk factors, these findings should be interpreted with caution."

Mortality from circulatory system diseases and low-level radon exposure in the French cohort study of uranium miners, 1946-1999, by Nusinovici S, Vacquier B, Leuraud K, et al., in: Scandinavian journal of work, environment & health , online-first, Jan. 26, 2010 (full text download free of charge)

German uranium miners' study provides some evidence of increased risk of extrapulmonary cancers associated with radon

Radon and risk of extrapulmonary cancers: results of the German uranium miners' cohort study, 1960-2003, by M Kreuzer, L Walsh, M Schnelzer, A Tschense and B Grosche, in: British Journal of Cancer Vol. 99 (2008), Published online 11 November 2008

Study finds increased mortality among Grants underground uranium miners, but not among uranium mill workers (New Mexico)

A cohort study of uranium millers and miners of Grants, New Mexico, 1979-2005, by Boice JD Jr, Cohen SS, Mumma MT, et al., in: Journal of Radiological Protection, Vol. 28 (2008), No. 3 (Sep), p. 303-325

Lung cancer among Wismut uranium miners

Lung cancer risk among German male uranium miners: a cohort study, 1946-1998, by B Grosche, M Kreuzer, M Kreisheimer, M Schnelzer and A Tschense, British Journal of Cancer advance online publication 17 October 2006

The German Uranium Miners Cohort Study (Wismut cohort), 1946–2003

Leukaemia among Wismut uranium miners

Leukemia and exposure to ionizing radiation among German uranium miners, by M Möhner, M Lindtner, H Otten, HG Gille; in: American Journal of Industrial Medicine, Vol. 49, No. 4, April 2006, p. 238-248

Leukaemia among Czech uranium miners

Abstract: The study presents recent findings in an extended cohort of miners, now including nearly 10000 uranium and 2000 tin miners and followed up to 1999. A total of 30 cases of leukaemia were observed among Czech uranium miners, corresponding to standardized mortality ratio of 1.5, 90%CI: 1.0-2.1. The risk is analyzed in relation to cumulated dose from radon, external gamma radiation and alpha radiation from long lived radionuclides contained in mining aerosol. Doses to red bone marrow were estimated using measurements of external gamma activities since the early 1960s and measurements of long lived radionuclides in the aerosol since the 1970s. The red bone marrow dose from inhaled long lived radionuclides is estimated by applying respiratory tract model and relevant biokinetic models. The substantial point is that the dose is cumulated even after the underground work has stopped. Another important point is the difference of the exposure by job category. By extrapolating available exposure data and applying models based on ICRP-66 and ICRP-68, individual doses were estimated using working histories, job matrix, and time since exposure. The cumulated red bone marrow dose includes external gamma radiation, dose from radon and its progeny, and committed equivalent dose from long lived alpha-emitters in dependence on the individual length of follow-up. The mean cumulated dose is 158 mSv. Among uranium miners, about 52% of the total dose is due to inhalation of uranium and its decay products with aerosol in mines, about 33% is due to gamma radiation, and some 15% of the dose is from radon and its progeny. The risk coefficient (excess relative risk per sievert) corresponding to these estimates in the present study is 3.1 (90%CI: 1.3 – 5.4). The estimated risk is subject to a considerable uncertainty, due to small numbers and the uncertainty in the estimated dose. However, the magnitude of the risk is consistent with estimates from other studies.

Leukaemia Among Czech Uranium Miners, by L. Tomášek, I. Malátová, in: Proceedings of the 9th International Conference on Health Effects of Incorporated Radionuclides Emphasis on Radium, Thorium, Uranium and their Daughter Products - HEIR 2004, GSF-National Research Center for Environment and Health, Neuherberg, Germany, Nov 29 - Dec 1, 2004, U. Oeh, P. Roth, H.G. Paretzke (Editors), Institut für Strahlenschutz, GSF-Bericht 06/05, p. 128-135
> Download full proceedings (4M PDF)

Long-term persistence of chromosome aberrations observed in Hungarian uranium miners

Long-term persistence of chromosome aberrations in uranium miners, by G Mészáros, G Bognár, GJ Köteles, in: Journal of Occupational Health Vol. 46, No. 4 (July 2004), p. 310-315.

Study Group: Contemporary Saskatchewan uranium miners' health study not scientifically feasible

"It concludes that it is not scientifically feasible to conduct a study of present and future miners who work in modern Saskatchewan uranium mines (1975 onward). Today’s Saskatchewan uranium miners have radon exposures that are between 100 and 1000 times lower than those of past uranium miners, such as miners from Beaverlodge, because of dose limits, improved mining techniques, and other radiation protection practices. Any higher-than-normal rates of lung cancer from such workplace exposures would be virtually impossible to measure. The feasibility study was completed in October 2003 and it was then reviewed by three internationally respected radiation researchers."

The Study Group comprises representatives from the Canadian Nuclear Safety Commission, the Government of Saskatchewan, and two mining companies involved in uranium mining in Saskatchewan (Cogema Resources Inc. and Cameco Corporation).

> View CNSC release (June 18, 2004) · CNSC backgrounder (June 22, 2004)

Chromosomal aberrations with former Wismut uranium miners similar to those with coal miners

"PURPOSE: To compare chromosomal aberrations in peripheral lymphocytes of Wismut uranium miners (WUM) and Ruhr coal miners (RCM).
MATERIALS AND METHODS: Peripheral lymphocytes from 66 WUM and 29 RCM were cultured and analysed for structural chromosomal aberrations in Giemsa-stained M1 metaphases. Cytogenetic data from 23 male white-collar workers from public services were used as a historical control group.
RESULTS: The frequencies of chromosomal aberrations and sister chromatid exchanges in WUM and RCM were quite similar. Compared with public services workers, WUM and RCM had significantly higher frequencies of chromosomal aberrations.
CONCLUSIONS: Chromosomal aberrations in WUM are not induced by radioactive particles inhaled during underground mining but as in RCM rather result from factors such as age, lifestyle, illnesses, medications and diagnostic irradiations."

Reference:
Chromosomal aberrations in uranium and coal miners, by G. Wolf, D. Arndt, N. Kotschy-Lang, G. Obe;
International Journal of Radiation Biology, February 2004, Vol. 80, No. 2, p. 147-153

Chromosomal aberrations with former Czech uranium miners

"[...] In the present study, we analyzed data on 1323 cytogenetic assays and 225 subjects examined because of occupational exposures to radon (range of exposure from 1.7 to 662.3 working level month (WLM)). Seventy-five subjects were non-smokers. We found 36 cases of cancer in this cohort.Chromatid breaks were the most frequently observed type of aberrations (mean frequency 1.2 per 100 cells), which statistically significantly correlated with radon exposure (Spearman's correlation coefficient R=0.22, P<0.001). Also, the frequency of aberrant cells (median of 2.5%) correlated with radon exposure (Spearman's correlation coefficient R=0.16, P<0.02). [...]"

Chromosomal aberrations with former Wismut uranium miners

"PURPOSE: To assess the long-term effect of radiation exposure of uranium miners on a cytogenetic endpoint: micronuclei (Mn) with and without a centromere.
MATERIALS AND METHODS: Mn were scored using the cytochalasin-B technique. It is known that Mn can comprise acentric fragments or/and whole chromosomes. Mn containing whole chromosomes were identified by means of fluorescence in situ hybridization (FISH) with a centromere-specific probe. The frequency and percentage of Mn were analysed with centromeres (MnC+) in lymphocytes of healthy donors and uranium miners with large radiation exposures several decades ago employed by the Wismut AG in the former German Democratic Republic. The miners were subdivided into those with and those without bronchial carcinoma.
RESULTS: It was shown previously that the relative frequency of MnC+ decreased with dose; this means that the number of Mn originating from acentric fragments increases. In the study presented here, no statistically significant difference in the overall Mn frequency was seen between the analysed groups. The fraction of MnC+, however, was highest in lymphocytes of healthy male donors (mean: 74.6%) followed by healthy miners (mean: 62.1%) and those suffering from cancer (mean: 55.8%).
CONCLUSION: The results indicate the occurrence of a genomic instability in lymphocytes of miners, especially those with cancer. It appears that the low percentage of MnC+ may be a marker of genomic instability and cancer predisposition."

Reference:
A cytogenetic analysis of the long-term effect of uranium mining on peripheral lymphocytes using the micronucleus-centromere assay,
by Kryscio A, Ulrich Müller WU, Wojcik A, Kotschy N, Grobelny S, Streffer C.
International Journal of Radiation Biology, November 2001; Vol.77, No.11, p. 1087-1093

Pulmonary fibrosis with uranium miners caused from inhalation of radon progeny

"Many uranium miners have been disabled by and died of pulmonary fibrosis that was not recognized as an occupational disease. A review of animal studies, complications from whole body irradiation, pulmonary function, and mortality studies of uranium miners led us to suspect radiation-induced chronic diffuse interstitial fibrosis in miners who had inhaled excessive radon progeny. A selected group of uranium miners (22) with severe respiratory disease (but no rounded nodules in chest films) were studied. Lung tissue from five disclosed severe diffuse interstitial fibrosis, with "honeycomb lung" in all. Some also had small anthrasilicotic nodules and birefringent crystals. Although quartz crystals probably contributed, we concluded that the predominant injurious agent in these cases was alpha particles from radon progeny. This disease, after a long latent period, usually results in pulmonary hypertension, shortness of breath, and death by cardiopulmonary failure."

Reference:
Archer VE et al: Chronic diffuse interstitial fibrosis of the lung in uranium miners.
Journal of Occupational and Environmental Medicine, Vol. 40, No. 5, May 1998 May, p.460-474

Native American uranium miners experience higher risk of nonmalignant respiratory disease

Uranium mining is more strongly associated with obstructive lung disease and radiographic pneumoconiosis in Native Americans than in Hispanics and non-Hispanic Whites. Obstructive lung disease in Hispanic and non-Hispanic White miners is mostly related to cigarette smoking. Current compensation criteria excluded 24% of Native Americans who, by ethnic-specific standards, had restrictive lung disease and 4.8% who had obstructive lung disease. Native Americans have the highest prevalence of radiographic pneumoconiosis, but are less likely to meet spirometry criteria for compensation.

Reference:
Mapel, DW; Coultas, DB; James, DS; et al.: Ethnic differences in the prevalence of nonmalignant respiratory disease among uranium miners, in: American Journal of Public Health, Vol. 87, 1997, No. 5 (May), p.833-838

Chromosomal Aberrations With Namibian Uranium Mine Workers

Verification study finds no excess chromosomal aberrations in Namibian uranium miners

"On 22 June 2000 Drs Lloyd and Lucas, the two international experts appointed by Rössing Uranium Ltd and the branch executive of the Mineworkers Union of Namibia (MUN), announced in Windhoek the results of the Verification Study on the effects of long-term, low dose radiation exposure.

The purpose of the study was to confirm or refute the study findings on radiation exposure of Dr Reinhard Zaire, the retained expert of the MUN. Dr Zaire's findings suggested that there was a high incidence of chromosomal aberrations among Rössing employees due to long-term, low dose radiation exposure. The experts refuted Dr Zaire's findings and stated in the report: 'The overall conclusion is that the frequency of chromosomal damage in the miners did not exceed that in the control subjects. This verification study has therefore not confirmed the earlier report of Dr Zaire and his colleagues.' [...]

To implement the study, blood samples were obtained from two groups, namely the study group and the control group. The study group consisted of ten Rössing employees with the highest accumulated radiation dose, and the control group of ten individuals from communities at the coast with no connection to Rössing. All participants were screened for suitability to participate in the study according to the selection criteria prescribed by the two experts and agreed by the Rössing and the MUN."
(from Rössing/MUN media release, June 30, 2000)

Excess chromosomal aberrations found in Namibian uranium miners

Analysis of white blood cells from uranium mineworkers in Namibia for chromosomal and phenotypic alterations

(excerpt from poster presented by R.Zaire et al. at the Congress of German and Austrian Oncologists in Hamburg, 8 Oct 1995)

Introduction

Workers of the open cast uranium mine in Namibia suffer from health problems including malignant diseases at a much higher prevalence compared to the general population. Exact epidemiological data on this subject do not exist.

Objectives

The objective of the study is to determine whether exposure of miners to uranium increases the risk of biological radiation damage which may lead to malignant diseases. An increase in chromosomal abnormalities represents a major risk factor for the development of a malignancy.

Material and Methods

Study population

The study group comprises 75 male uranium open cast miners who were employed in different sections of the mine. Annual exposure varied considerably and was highest (~6 mSv for 20 workers) in the Final Plant Recovery. All persons examined were healthy and no one had previously received radiation or cytostatic therapy. No virus infections were recorded for the 3 weeks prior to blood sampling. The 75 miners were compared to a control group of 31 individuals with no occupational history in mining living in Namibia remote from the uranium cast.

Neutrophil counts and immunophenotyping

[...]

Cytogenetic studies with FISH

[...]

Results

1. Neutrophil counts and immunophenotype

In the miners, n=75, the absolute neutrophil counts were significantly decreased compared to the control group (n=31), (2.4 +/- 0.94 / nl versus 3.1 +/- 1.43 / nl, x mean +/- SD, p=0.0036).
CD4 and CD8 cell counts, as well as NK cell counts were in normal range.

2. Cytogenetics

Quantitative and qualitative genomic alterations were investigated in representative cohorts using the Fluorescence-in-situ-Hybridization (FISH) method. In the miner's group 0.81 +/- 0.20 (x mean +/- SD) chromosomal aberrations per 100 cells were recorded and compared to a control group, 0.45 +/- 0.15 (x mean +/- SD) (p=0.0031). This represents a two-fold increase of the total number of all chromosomal aberrations recorded in peripheral lymphocytes of mineworkers versus the unexposed individuals.

Discussion

While the determination of chromosome aberrations have been made using conventional staining of chromosome banding, the effort required has prevented wide-scale exploration and applications of this approach. The recent development of FISH for chromosome staining has significantly improved the situation. The main advantage of FISH-based translocation analysis is that the aberrations are made distinct so that they can be scored rapidly. In addition, discrimination between translocations and dicentrics can be done accurately using centrometric staining with a pan-centromere probe. This is particularly important when the translocation and dicentric frequencies are of similar magnitude (e.g. in analysis of cells at first division within a few weeks after radiation exposure). Chromosome alteration analysis also may be useful in studies of chronically exposed populations because stable aberrations such as translocations are expected to accumulate during exposure.

Conclusion

Here we conlude that:

• FISH-method is useful for detection of genomic alterations in white blood cells of radiation-exposed people
• ²³⁸U-exposed miners have a higher chromosomal aberrations in their lymphocytes which may be indicative for an increased risk for malignancy.

Contact:
Reinhard Zaire
Dept. of Hematology and Oncology
University Medical Centre Benjamin Franklin
Free University Berlin
Hindenburgdamm 30, D-12200 Berlin, Germany
Tel. +49-30-8445-2931, Fax: +49-30-8445-4468

References:
Zaire, R; Notter, M; Riedel, W; Thiel, E: Unexpected rates of chromosomal instabilities and alterations of hormone levels in Namibian uranium miners, in: Radiation Research Vol. 147, 1997, No. 5 (May); p.579-584

Zaire,R; Griffin,C S; Simpson,P J; et al.: Analysis of lymphocytes from uranium mineworkers in Namibia for chromosomal damage using Fluorescence in-situ Hybridization (FISH), in: Mutation Research-Genetic Toxicology Vol. 371, 1996, No.1-2, p.109-113

Zaire,R; Notter,M; Riedel,W; Thiel,E: Determination of uranium excretion, gonadal damage and chromosomal alterations among uranium miners in Namibia, in: Blood Vol. 86, 1995, No.10, p.153

Risk of Cancer Incidence other than Lung Cancer with Uranium Mine and Mill Workers

Summary

"After the reunification of Germany the so-called Hauptverband der gewerblichen Berufsgenossenschaften (HVBG) is the responsible German institution for the acknowledgement of occupational diseases and the compensation of workers at the previous WISMUT uranium mining company in East Germany. On behalf of the HVBG in an earlier study already an analysis of the possible lung cancer risk of these uranium miners due to their exposure to radon progeny has been carried out (Jacobi et al., GSF Report S-14, 1992). In the last years an increasing number of other cancer cases among these miners have been submitted for compensation. The HVBG, therefore, has requested a similar expertise for the possible radiation risk and probability of causation of extrapulmonary cancers among the WISMUT uranium workers. In the following report the methods and main results of this risk analysis are discribed.

For the evaluation of the lung cancer risk from inhaled radon progeny direct epidemiological data from other groups of uranium miners are available. These data yield, however, no quantitative evidence for extrapulmonary cancers. Therefore, in this study an indirect dosimetric approach for the evaluation of the possible excess relative risk (ERR) of extrapulmonary cancers among the WISMUT workers was applied. In this approach the following exposure pathways are taken into account: (1) The inhalation of radon and its short-lived progeny; (2) the inhalation of uranium (U-238, U-235) and its decay products with the ore dust; and (3) the tissue doses from external gamma and beta radiation. Tissue doses from inhaled radionuclides were calculated applying the new respiratory tract model recommended in ICRP Publication 68 (1994). The evaluation of the attributed ERR proceeds from the recently published data of the Life Span Study on the excess cancer incidence in the atomic bomb survivors, taking into account a DDREF of 2 and a radiation weighting factor of 20 for alpha radiation. For solid cancers a time-constant relative risk model was used, whereas for leukemias, lyphomas and myelomas the variation of the ERR with time since exposure was taken into regard.

Central best estimates of the resulting ERR and the attributed probability of causation of extrapulmonary cancers are given for typical exposure conditions of the WISMUT uranium miners, particularly for the critical years 1946-55. For most extrapulmonary cancer types the ERR values are more than a factor of 10 lower than the corresponding value for lung or bronchial cancer, respectively. The only exemption concerns cancers in the extrathoracic region (mouth region, pharynx and larynx) for which the ERR is only about a factor of 5 lower than the ERR for lung cancer.

Finally, general conclusions and recommendations for the decision making in the individual acknowledgement procedure are outlined." [Jacobi1995]

Expected excess relative risk (ERR) and probability of causation (PoC) for solid cancers due to one year of underground work in the period 1946-55, central best estimates for WISMUT-hewers, for an age at exposure of 25 years and a time after exposure of 30-60 years (excerpt of Table 6.1 [Jacobi1995]):

 cancer location                  ERR       PoC
-------------------------------------------------
lung, total                       4.0       80%
lung, bronchial epithelium        5.8       85%
mouth region, pharynx, larynx     0.8       45%
bone, connective tissue           0.3       25%
liver                             0.10       9%
kidney                            0.06       6%

For leukemia, the excess relative risk is higly depending on the time since exposure. For the miners who worked in the period 1946-55, a significant increase of leukemia incidence is expected for the period 10-20 years after exposure, but there is no epidemiologic data available for that period. In our days, i.e. 40-50 years after exposure, the expected ERR after one year of work is around 0.12, the probability of causation around 10%.

The conclusion of the analysis is that

• an observed cancer of the mouth region, pharynx, and larynx has a probability of causation from the occupational exposure at WISMUT of 50% already after slightly more than one year of underground work;
• for bone and connective tissue cancers, the same probability of causation is expected after 4-8 years of underground work;
• for leukemia, liver and kidney cancer, a probability of causation of 25-50% can be expected after many years of underground work.

In a second study [Jacobi1997], Jacobi et al. performed a more detailed assessment of bone and liver cancers.

from the Summary:

"In the latter report (Jacobi et al. 1995) the risk coefficients resulting from the Life Span Study of the atomic bomb survivors have been applied, taking into account a radiation weighting factor of 20 for the alpha ray exposure of the WISMUT miners. In the conclusions of this report it was recommended to consider in the case of bone and liver cancer in addition also the available direct epidemiological data from internal alpha emitters. This is the objective of the now submitted report.

In the first part the relevant data from epidemiological studies on bone cancer (radium-224 patients, radium workers) and on liver cancer (Thorotrast patients) are summarized. On the basis of these findings empirical models for the evaluation of the excess absolute risk rate as function of activity intake and time since exposure or the attained age, respectively, are developed for the relevant radionuclides. In this procedure the new biokinetic and dosimetric models proposed by ICRP Committee 2 are taken into account. For the calculation of the excess relative risk and the corresponding probability of causation the incidence data on bone and liver cancer from the DDR Cancer Registry are used as normal background rate.

The application of these risk models to the exposure conditions of WISMUT workers takes into regard the inhalation of radon-222 and its progeny (including lead-210), the inhalation of U- containing ore dust with large particle sizes and the external gamma radiation at the workplace." [Jacobi1997]

The critical group are the employees who were exposed at the age of around 20 years. For this group, the excess relative risk (ERR) of contracting liver cancer from one year of work at WISMUT during the period 1946 - 1955 reaches values of 2 - 7 at the age of 35 - 55, corresponding to a probability of causation (PoC) of 65 - 87%. For bone cancer, the ERR is much lower and reaches 0.4 - 0.8 at the age of 30 - 50, corresponding to a PoC of 28 - 45%.
The excess relative risk of contracting liver cancer from the occupational exposure at WISMUT thus is 20 - 70 times higher than estimated in the previous study.

The models are available online in the Uranium Miner Health Risk Calculator.

Sources:
[Jacobi1995] W.Jacobi, P.Roth: Risiko und Verursachungs- Wahrscheinlichkeit von extrapulmonaren Krebserkrankungen durch die berufliche Strahlenexposition von Beschäftigten der ehemaligen WISMUT AG, [Risk and Probability of Causation of Extrapulmonary Cancers due to the Occupational Radiation Exposure of Workers at the previous WISMUT Uranium Mining Company], 86 pages in German, GSF-Bericht 4/95, GSF-Forschungszentrum für Umwelt und Gesundheit , Oberschleißheim 1995.

[Jacobi1997] W.Jacobi, P.Roth, D.Noßke: Mögliches Risiko und Verursachungs-Wahrscheinlichkeit von Knochen- und Leberkrebs durch die berufliche Alphastrahlen-Exposition von Beschäftigten der ehemaligen WISMUT AG [Possible Risk and Probability of Causation of Bone and Liver Cancer due to the Occupational Alpha Ray Exposure of Workers at the previous WISMUT Uranium Mining Company], 57 pages in German, Forschungsbericht, GSF- Forschungszentrum für Umwelt und Gesundheit , Oberschleißheim, July 1997

New Model for Assessment of Lung Cancer Incidence with Uranium Miners

Prof. Wolfgang Jacobi, former director of the Institut für Strahlenschutz of the GSF - Forschungszentrum für Umwelt und Gesundheit GmbH (Institute for Radiation Protection of the GSF - Research Center for Environment and Health Ltd.) in Neuherberg, Germany, has analysed radiation exposure data of East Germany's uranium mining company Wismut, to find criteria for the recognition of lung cancers as occupationally caused or not. He developed a model that relates a lung cancer incidence to the work at Wismut for much lower doses than previously thought.

Since there is no personal data available on radon decay product exposure for the Wismut workers, general guidelines have to be found for the recognition of lung cancers as occupation related. During Wismut's early years 1946-1955, average annual exposure to radon daughters for miners is estimated at around 100-250 WLM (Working Level Month). This average exposure corresponds to radon concentrations in air of around 100,000 Bq/m³, while maximum radon concentrations reached 2 million Bq/m³. Between 1956 and 1970, radon daughter exposure strongly decreased, and since 1970 average annual exposure is around 4 WLM.
Based on epidemiological data from uranium miner studies published in literature, Jacobi developed a ZSE (time since exposure)-model to determine the lung cancer rate depending on exposure, age at exposure and age at lung cancer incidence. Due to insufficient data, the model makes no difference between smokers and non-smokers.

The results of the model are discussed for the following cases:

1. For miners who worked at least one year between 1946 and 1955 (and thus at least received around 200 WLM), the probability of causation for a lung cancer as occupation related is greater than 50%, independent of the age at lung cancer incidence.
2. For miners who worked during five years between 1956 and 1960 and thus accumulated around 190 WLM, the probability of causation for a lung cancer as occupation related is greater than 50%, independent of the age at exposure and at lung cancer incidence.
3. For those who worked during five years between 1961 and 1965 and thus accumulated around 90 WLM, the probability of causation for a lung cancer as occupation related is greater than 50% only, if lung cancer incidence was around 7-20 years after exposure.
4. For those who worked during five years between 1966 and 1970 and thus accumulated around 30 WLM, the probability of causation for a lung cancer as occupation related is greater than 50% only, if the age at exposure was 20-40 and if lung cancer incidence was around 10-20 years after exposure.
5. For those who worked since 1970 and thus accumulated around 4 WLM per year, the probability of causation for a lung cancer as occupation related is dependant on period of exposure, age at exposure and age at lung cancer incidence. For example:
   • After ten years of exposure and accumulation of 40 WLM, the probability of causation is only greater than 50%, if the age at exposure was 20 and the age at lung cancer incidence was 33-43, or if the age at exposure was 30 and the age at lung cancer incidence was 44-51.
     
   • After 30 years of exposure and accumulation of 120 WLM, the probability of causation is greater than 50%, if the age at exposure was 20 and the age at lung cancer incidence was 33-70, or if the age at exposure was 30 and the age at lung cancer incidence was 44-76.

With this model, the employers' liability insurance association, who has to pay for the compensation of occupationally caused diseases, has a first guideline for the assessment of lung cancers with Wismut miners.

A comparison of Jacobi's model with the BEIR IV model of 1988 is presented in [2].

It is worth noting that, according to this model, already an exposure of 30 WLM may be regarded as a cause of a lung cancer incidence, depending on age at exposure and age at cancer incidence. According to recognition practice under the GDR-era, at least 150 WLM of exposure were necessary for recognition (during the early years, the limit even was at 450 WLM). With this limit, no worker had a chance for recognition, if he had worked for example only after 1970. With the new model, all cases of lung cancer that were not recognized, have to be reassessed.

It's also interesting to compare the results of this model to the regulations met in the US Radiation Exposure Compensation Act of 1990. According to the original version of this act, only those miners who worked between 1947 and 1971 and received at least 200 WLM (non-smokers), 300 WLM (smokers with incidence before age 45), 500 WLM (other smokers) and developed lung cancer or a nonmalignant respiratory disease, should receive compensation. In 2002, the exposure threshold was lowered to 40 WLM for all miners.
> Compensation of Navajo Uranium Miners

The model is available online in the Uranium Miner Health Risk Calculator.

Sources:
[1] W.Jacobi, K.Henrichs, D.Barclay: Verursachungs- Wahrscheinlichkeit von Lungenkrebs durch die berufliche Strahlenexposition von Uran-Bergarbeitern der WISMUT AG, [Probability of causation for lung cancer due to the occupational radiation exposure of uranium miners of WISMUT AG], 67 pages in German, GSF-Bericht S-14/92, Neuherberg 1992.
Order address: GSF - Forschungszentrum für Umwelt und Gesundheit GmbH, Neuherberg, Ingolstädter Landstraße 1, D-85764 Oberschleißheim, Germany.
Tel. +49-89-3187-4011, Fax: +49-89-3187-3323

[2] Chmelevsky,D. et al.: Probability of causation for lung cancer after exposure to radon progeny: a comparison of models and data; in: Health Physics Vol.67, No.1, July 1994, p.15-23

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