Application of an informatics-based decision-making framework and process to the assessment of radiation safety in nanotechnology.

The National Council on Radiation Protection and Measurements (NCRP) established NCRP Scientific Committee 2-6 to develop a report on the current state of knowledge and guidance for radiation safety programs involved with nanotechnology. Nanotechnology is the understanding and control of matter at the nanoscale, at dimensions between ∼1 and 100 nm, where unique phenomena enable novel applications. While the full report is in preparation, this paper presents and applies an informatics-based decision-making framework and process through which the radiation protection community can anticipate that nano-enabled applications, processes, nanomaterials, and nanoparticles are likely to become present or are already present in radiation-related activities; recognize specific situations where environmental and worker safety, health, well-being, and productivity may be affected by nano-related activities; evaluate how radiation protection practices may need to be altered to improve protection; control information, interpretations, assumptions, and conclusions to implement scientifically sound decisions and actions; and confirm that desired protection outcomes have been achieved. This generally applicable framework and supporting process can be continuously applied to achieve health and safety at the convergence of nanotechnology and radiation-related activities.

Updated mortality analysis of radiation workers at Rocketdyne (Atomics International), 1948-2008.

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

The role of dose-rate on risk from internally-deposited radionuclides and the potential need to separate dose-rate effectiveness factor (DREF) from the dose and dose-rate effectiveness factor (DDREF).

In 1980, National Council on Radiation Protection and Measurements suggested the term dose-rate effectiveness factor (DREF) to describe the reduction of effectiveness of protracted radiation in producing biological damage and risk. A nonlinear decrease in damage was also noted following low total doses. The International Commission on Radiological Protection therefore combined the influence of low dose and low dose-rate and assigned a single value of 2.0 for a dose and dose-rate effectiveness factor (DDREF) to be applied for estimating risk for both low total dose and low dose-rate exposures. This paper re-evaluates one extensive data set on inhaled radionuclides in dogs which suggests that there may be a need to separate these factors (DREF and DDREF) for larger protracted doses from internally-deposited radioactive materials. Extensive recent research on the mechanisms of action of both low dose and low dose-rate radiation exposure at the molecular, cellular, and animal level of biological organization suggest that the influence of protraction of radiation may be large and variable, due to adaptive and protective responses, following very low doses and dose-rate exposures. Important observations in this paper in dogs exposed by inhalation to beta-gamma emitting radionuclides include (1) discontinuities in the data sets as a function of both dose and dose-rate suggesting shifts in mechanisms of action following high doses from protracted exposure away from those postulated for cancer from low total doses; (2) no increase in non-neoplastic disease, cancer frequency, or life-shortening following low dose-rate exposures to high total lung doses (up to 25 Gy); (3) all dogs that received doses below 25 Gy were combined and a decrease in the frequency of lung cancer in these exposed animals relative to the controls was noted, while very large doses from all radionuclides studied resulted in very marked increases in lung cancer; (4) a significant increase in hemangiosarcoma in the heart and tracheobronchial lymph nodes was observed after very high doses; (5) in this paper the DREF for lung cancer in dogs relative to single acute radiation exposure was as high as 35; and (6) the amount of life-shortening increased per unit dose as a function of the half-life with (90)Y being eight times as effective per unit of dose as (90)Sr. Such information suggests that there may be a need to assign different values for DDREF and DREF, especially in situations where there are large nonuniform total doses delivered by internally-deposited radionuclides. This is extremely important since the risk from radiation exposure from internally-deposited radionuclides in the lungs following nuclear fallout, accidents and terrorist activities may be much less than currently projected.

Radiotoxicity of inhaled (239)PuO(2) in dogs.

Beagle dogs inhaled graded exposure levels of insoluble plutonium dioxide ((239)PuO(2)) aerosols in one of three monodisperse particle sizes at the Lovelace Respiratory Research Institute (LRRI) to study the life-span health effects of different degrees of alpha-particle dose non-uniformity in the lung. The primary noncarcinogenic effects seen were lymphopenia, atrophy and fibrosis of the thoracic lymph nodes, and radiation pneumonitis and pulmonary fibrosis. Radiation pneumonitis/ pulmonary fibrosis occurred from 105 days to more than 11 years after exposure, with the lowest associated alpha-particle dose being 5.9 Gy. The primary carcinogenic effects also occurred almost exclusively in the lung because of the short range of the alpha-particle emissions. The earliest lung cancer was observed at 1086 days after the inhalation exposure. The most common type seen was papillary adenocarcinoma followed by bronchioloalveolar carcinoma. These lung cancer results indicate that a more uniform distribution of alpha-particle dose within the lung has an equal or possibly greater risk of neoplasia than less uniform distributions of alpha-particle dose. The results are consistent with a linear relationship between dose and response, but these data do not directly address the response expected at low dose levels. No primary tumors were found in the tracheobronchial and mediastinal lymph nodes despite the high alpha-particle radiation doses to these lymph nodes, and no cases of leukemia were observed.

Mortality among radiation workers at Rocketdyne (Atomics International), 1948-1999.

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

A comprehensive dose reconstruction methodology for former rocketdyne/atomics international radiation workers.

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