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(last updated 18 Oct 2006)
Contents:
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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 Canceradvance online publication 17 October 2006
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
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. Tomáek, 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 in uranium miners, by G Mészáros, G Bognár, GJ Köteles, in: Journal of Occupational Health Vol. 46, No. 4 (July 2004), p. 310-315.
"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."Therefore, an ongoing health study of modern Saskatchewan uranium miners will not be conducted.
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)
"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
"[...] 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). [...]"Reference:
"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
"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
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
"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.> See also: Lloyd, D. C., Lucas, J. N., Edwards, A. A., Deng, W., Valente, E., Hone, P. A. and Moquet, J. E.: A Study to Verify a Reported Excess of Chromosomal Aberrations in Blood Lymphocytes of Namibian Uranium Miners. Radiation Research Vol. 155 No. 6 (June 2001), p.807-817, ISSN 0033-7587The 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)
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: +49-30-8445-4468References:
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.579-584Zaire,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
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
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:
[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
[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.
,
Oberschleißheim, July 1997
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:
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:
[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
[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
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