Building a job-exposure matrix for early plutonium workers at the Sellafield nuclear site, United Kingdom.

The potential for adverse health effects from internal exposure to Plutonium has been recognised since its discovery in the 1940s. However, in the absence of specific information, potential risks from Plutonium exposure have always largely been controlled through knowledge of radiation exposure risks in general, much of which comes from external radiation exposures. To try to obtain more direct estimates of potential internal exposure risks, epidemiological studies of Plutonium workers need to be conducted. Such epidemiological analyses require individual Plutonium exposure estimates that are as accurate and unbiased as possible. The UK Sellafield workforce includes one of the world's largest cohorts of Plutonium workers, which constitutes, by some considerable margin, the group of workers most comprehensively monitored for internal exposure to this alpha-particle-emitter. However, for several hundred workers employed at the start of Plutonium work at the facility, during the period from 1952 through to 1963, the historical urinalysis results available cannot provide sufficiently accurate and unbiased exposure assessments needed for use in epidemiological studies. Consequently, these early workers have had to be excluded from epidemiological analyses and this has significantly reduced the power of these studies. A promising quantitative methodology to overcome the issue of missing or deficient exposure data, is to use exposure data from other sources to estimate the average exposure a 'typical worker' would have received, and to collate this information for specific occupations and years. This approach is called a Job-Exposure Matrix (JEM). Work on a pilot study to construct a population-specific quantitative JEM for the early Plutonium workers at Sellafield during 1952-1963, for whom reliable urinalysis results do not exist, has shown the potential for a JEM approach to produce more reliable and useful exposure estimates for epidemiological research.

Chromosome aberrations in workers occupationally exposed to tritium.

This paper reports the findings of an historical chromosome analysis for unstable aberrations, undertaken on 34 nuclear workers with monitored exposure to tritium. The mean recorded ß-particle dose from tritium was 9.33 mGy (range 0.25-79.71 mGy) and the mean occupational dose from external, mainly γ-ray, irradiation was 1.94 mGy (range 0.00-7.71 mGy). The dicentric frequency of 1.91 ± 0.53 × 10-3 per cell was significantly raised, in comparison with that of 0.61 ± 0.30 × 10-3 per cell for a group of 66 comparable worker controls unexposed to occupational radiation. The frequency of total aberrations was also significantly higher in the tritium workers. Comparisons with in vitro studies indicate that at these dose levels an increase in aberration frequency is not expected. However, the available historical tritium dose records were produced for the purposes of radiological protection and based on a methodology that has since been updated, so tritium doses are subject to considerable uncertainty. It is therefore recommended that, if possible, tritium doses are reassessed using information on historical recording practices in combination with current dosimetry methodology, and that further chromosome studies are undertaken using modern FISH techniques to establish stable aberration frequencies, as these will provide information on a cumulative biological effect.

Risk of Lung Cancer Mortality in Nuclear Workers from Internal Exposure to Alpha Particle-emitting Radionuclides.

BACKGROUND: Carcinogenic risks of internal exposures to alpha-emitters (except radon) are poorly understood. Since exposure to alpha particles-particularly through inhalation-occurs in a range of settings, understanding consequent risks is a public health priority. We aimed to quantify dose-response relationships between lung dose from alpha-emitters and lung cancer in nuclear workers. METHODS: We conducted a case-control study, nested within Belgian, French, and UK cohorts of uranium and plutonium workers. Cases were workers who died from lung cancer; one to three controls were matched to each. Lung doses from alpha-emitters were assessed using bioassay data. We estimated excess odds ratio (OR) of lung cancer per gray (Gy) of lung dose. RESULTS: The study comprised 553 cases and 1,333 controls. Median positive total alpha lung dose was 2.42 mGy (mean: 8.13 mGy; maximum: 316 mGy); for plutonium the median was 1.27 mGy and for uranium 2.17 mGy. Excess OR/Gy (90% confidence interval)-adjusted for external radiation, socioeconomic status, and smoking-was 11 (2.6, 24) for total alpha dose, 50 (17, 106) for plutonium, and 5.3 (-1.9, 18) for uranium. CONCLUSIONS: We found strong evidence for associations between low doses from alpha-emitters and lung cancer risk. The excess OR/Gy was greater for plutonium than uranium, though confidence intervals overlap. Risk estimates were similar to those estimated previously in plutonium workers, and in uranium miners exposed to radon and its progeny. Expressed as risk/equivalent dose in sieverts (Sv), our estimates are somewhat larger than but consistent with those for atomic bomb survivors.See video abstract at, http://links.lww.com/EDE/B232.

Chromosome analysis in a case of a plutonium contaminated wound.

Chromosome analysis of peripheral blood lymphocytes was undertaken over a 10 year period following an intake of plutonium through a hand wound. Frequencies of cells with unstable complex aberrations remained high throughout this time, probably reflecting direct exposure of lymphocytes as they passed plutonium which had transferred to regional lymph nodes. Analysis at the final sampling time also revealed cells with stable aberrations at a much higher frequency relative to the number of unstable cells than expected from direct exposure, and is therefore most likely to be reflecting exposure to lymphocyte precursor cells from plutonium that has become deposited on bone surfaces.

A review of job-exposure matrix methodology for application to workers exposed to radiation from internally deposited plutonium or other radioactive materials.

Any potential health effects of radiation emitted from radionuclides deposited in the bodies of workers exposed to radioactive materials can be directly investigated through epidemiological studies. However, estimates of radionuclide exposure and consequent tissue-specific doses, particularly for early workers for whom monitoring was relatively crude but exposures tended to be highest, can be uncertain, limiting the accuracy of risk estimates. We review the use of job-exposure matrices (JEMs) in peer-reviewed epidemiological and exposure assessment studies of nuclear industry workers exposed to radioactive materials as a method for addressing gaps in exposure data, and discuss methodology and comparability between studies. We identified nine studies of nuclear worker cohorts in France, Russia, the USA and the UK that had incorporated JEMs in their exposure assessments. All these JEMs were study or cohort-specific, and although broadly comparable methodologies were used in their construction, this is insufficient to enable the transfer of any one JEM to another study. Moreover there was often inadequate detail on whether, or how, JEMs were validated. JEMs have become more detailed and more quantitative, and this trend may eventually enable better comparison across, and the pooling of, studies. We conclude that JEMs have been shown to be a valuable exposure assessment methodology for imputation of missing exposure data for nuclear worker cohorts with data not missing at random. The next step forward for direct comparison or pooled analysis of complete cohorts would be the use of transparent and transferable methods.

Construction, Validation and Sensitivity Analyses of a Job Exposure Matrix for Early Plutonium Workers at the Sellafield Nuclear Site, United Kingdom.

Plutonium is a radiologically significant alpha-particle emitter. The potential for adverse health effects from internal exposures due to plutonium intakes has been recognized since the 1940s. The workforce of the Sellafield nuclear facility (Cumbria, UK), includes one of the world's most important groups of plutonium-exposed workers for studying the potential health risks of this internal exposure. However, for several hundred workers employed at the start of plutonium work at the facility (1952-1963), historical monitoring records based on measurements of urinary excretion of plutonium are not sufficiently reliable to provide the accurate and unbiased exposure assessments needed for epidemiological studies. Consequently, these early workers have had to be excluded from such studies, significantly reducing their power. We constructed a population-specific quantitative job exposure matrix (JEM) to estimate the average intakes of "typical plutonium workers" in this period, from 1952-1963, and assessed its validity and sensitivity to exposure assessment decisions. We conducted internal cross-validation using an a priori 10% extracted sample to evaluate reliability of estimates, explored JEM sensitivity to assumptions in the exposure assessment, and assessed the impact of uncertainty in urinalysis measurements on the precision of annual intake estimates using Markov Chain Monte Carlo (MCMC) methodology. Pairwise correlations ( RP) of estimated (JEM) and measured (10% sample) annual intakes were moderate to high ( RP > 0.4) for 10 out of 13 JEM groups, while absolute differences were <20% for 11 out of 13 JEM groups. There was little evidence of a temporal trend in correlations ( P = 0.13) or absolute differences ( P = 0.34). The median JEM-derived cumulative intake of 95.2 (IQR, 55.0-130.0) Bq was comparable to those based on alternative assumptions in the exposure assessment (median range, 95.2-100.0 Bq; 75th percentiles, 130.0-146.0 Bq). Measurement error simulation resulted in a 40-60% reduced median cumulative intake but higher maximum cumulative intakes. The JEM finds a balance between reliability and precision that makes it useful for epidemiological purposes and is relatively insensitive to specific choices in the exposure assessment. This JEM will allow the inclusion of workers with longest follow-up and who could not be included up until now in epidemiological studies without introducing significant bias.

Reconstruction of Internal Doses for the Alpha-Risk Case-Control Study of Lung Cancer and Leukaemia Among European Nuclear Workers.

The Alpha-Risk study required the reconstruction of doses to lung and red bone marrow for lung cancer and leukaemia cases and their matched controls from cohorts of nuclear workers in the UK, France and Belgium. The dosimetrists and epidemiologists agreed requirements regarding the bioassay data, biokinetic and dosimetric models and dose assessment software to be used and doses to be reported. The best values to use for uncertainties on the monitoring data, setting of exposure regimes and characteristics of the exposure material, including lung solubility, were the responsibility of the dosimetrist responsible for each cohort. Among 1721 subjects, the median absorbed dose to the lung from alpha radiations was 2.1 mGy, with a maximum dose of 316 mGy. The lung doses calculated reflect the higher levels of exposure seen among workers in the early years of the nuclear industry compared to today.

FISH chromosome analysis of plutonium workers from the Sellafield nuclear facility.

Chromosome analysis using a single-color FISH technique to paint three pairs of chromosomes was undertaken on a group of 46 retired plutonium workers with assessed bone marrow doses >60 mSv, 34 of whom were categorized as having robust dosimetry and 12 for whom internal doses were considered less reliable. Comparisons were made with a group of 34 workers with negligible radiation exposure and a group of 34 workers with similar recorded external gamma-ray doses but negligible internal dose. The simple translocation frequency of 17.65 +/- 1.96 x 10(-3) per genome equivalent for the 34 plutonium workers with robust dosimetry was significantly increased in comparison with that of 10.06 +/- 1.16 x 10(-3) per genome equivalent for the unirradiated control group (P = <0.001) and that of 13.55 +/- 1.43 x 10(-3) per genome equivalent for the group with similar external gamma-ray exposure (P = 0.012). Thus, although in vitro studies have indicated that the majority of alpha-particle-irradiated cells suffer complex non-transmissible chromosome damage, in vivo a significant proportion survive with simple exchanges that can be passed on to descendant cells. In contrast, the three groups demonstrated no significant differences in stable complex aberrations. No evidence of an increase in dicentrics or unstable complex aberrations associated with plutonium exposure was observed, and it can therefore be assumed that there is little, if any, ongoing irradiation of mature lymphocytes. The translocation frequency of 12.08 +/- 1.92 x 10(-3) per genome equivalent for the group of 12 plutonium workers with less reliable internal dosimetry could adequately be accounted for by age and external dose and indicates that the internal bone marrow doses are likely to have been overestimated. Cytogenetic analysis can therefore make a valuable contribution to the validation of internal doses from plutonium deposition.

Chromosome aberrations determined by sFISH and G-banding in lymphocytes from workers with internal deposits of plutonium.

PURPOSE: To examine the influence of α-particle radiation exposure from internally deposited plutonium on chromosome aberration frequencies in peripheral blood lymphocytes of workers from the Sellafield nuclear facility, UK. MATERIALS AND METHODS: Chromosome aberration data from historical single colour fluorescence in situ hybridization (sFISH) and Giemsa banding (G-banding) analyses, together with more recent sFISH results, were assessed using common aberration analysis criteria and revised radiation dosimetry. The combined sFISH group comprised 29 men with a mean internal red bone marrow dose of 21.0 mGy and a mean external γ-ray dose of 541 mGy. The G-banding group comprised 23 men with a mean internal red bone marrow dose of 23.0 mGy and a mean external γ-ray dose of 315 mGy. RESULTS: Observed translocation frequencies corresponded to expectations based on age and external γ-ray dose with no need to postulate a contribution from α-particle irradiation of the red bone marrow by internally deposited plutonium. Frequencies of stable cells with complex aberrations, including insertions, were similar to those in a group of controls and a group of workers with external radiation exposure only, who were studied concurrently. In a similar comparison there is some suggestion of an increase in cells with unstable complex aberrations and this may reflect recent direct exposure to circulating lymphocytes. CONCLUSIONS: Reference to in vitro dose response data for the induction of stable aberrant cells by α-particle irradiation indicates that the low red bone marrow α-particle radiation doses received by the Sellafield workers would not result in a discernible increase in translocations, thus supporting the in vivo findings. Therefore, the greater risk from occupational radiation exposure of the bone marrow resulting in viable chromosomally aberrant cells comes from, in general, much larger γ-ray exposure in comparison to α-particle exposure from plutonium.