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Abstract: As with any medical treatment, the decision to excise a wound contaminated with actinides is a risk-benefit analysis. The potential benefits of surgical excision following such contaminated wounds are reduction in the probability of stochastic effects, avoidance of local effects, and psychological comfort knowing that radioactive material deposited in the wound is prevented from being systemic. These benefits should be balanced against the potential risks such as pain, numbness, infection, and loss of function due to excision. To that end, the responsibility of an internal dosimetrist is to provide advice to both the patient and the treating physician about the likely benefits of excision that include, but not limited to, averted doses. This paper provides a review of the effectiveness of surgical excisions following plutonium-contaminated wounds and finds that excisions are highly effective at removing plutonium from wounds and at averting the doses they would have caused., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Health Physics Society.)

Abstract: Anecdotal evidence indicates there may be unpublished physical and psychological events associated with the medical treatment of plutonium intakes. A thorough review was conducted of the medical and bioassay records of current and previous Los Alamos National Laboratory (LANL) employees who had experienced plutonium intakes via wound or inhalation. After finding relatively incomplete information in the medical records, the research team interviewed current LANL employees who had undergone chelation therapy and/or surgical excision. Although the dataset is not large enough to reach statistically significant conclusions, it was observed that adverse events associated with treatment appear to be more frequent and more severe than previously reported., Competing Interests: # The authors declare no conflicts of interest. ( Manuscript accepted 25 May 2022), (Copyright © 2022 Health Physics Society.)

Abstract: The objective of this paper is to compare post-2007 epidemiological results for plutonium workers to risk predicted by the software program NIOSH-IREP (IREP for short), which is used to determine the lowest dose for a US veteran to obtain cancer compensation. IREP output and methodology were used to predict excess relative risk per Gy (ERR Gy -1 ) for lung cancer at the 99 th credibility percentile, which is used for compensation decisions. Also estimated were relative biological effectiveness factors (RBE) predicted for workers using IREP methodology. IREP predictions were compared to results for Mayak and Sellafield plutonium workers, separately and pooled. Indications that IREP might underpredict 99 th -percentile lung cancer plutonium risk came from (1) comparison of worker RBEs and (2) from comparison of Sellafield results separately. When Sellafield and Mayak data were pooled, ERR Gy -1 comparisons at the 99 th percentile roughly matched epidemiological data with regression dose range restricted to < 0.05 Gy, the most relevant region to veterans, but overpredicted for the full dose range. When four plausible distributions for lung cancer risk, including both new and old data, were combined using illustrative weighting factors, compensation cutoff dose for lung cancer matched current IREP values unless regression results below 0.05 were chosen for Sellafield, producing a two-fold reduction. A 1997 claim of a dose threshold in lung cancer dose response was not confirmed in later literature. The benefit of the doubt is given to claimants when the science is unclear. The challenge for NIOSH-IREP custodians is dealing with the Sellafield results, which might best match US claimants., Competing Interests: The authors declare no conflicts of interest. Over the last 20 y, the author has prepared pro bono dose and risk analyses for four US veterans with a claim before the US Veterans Administration., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Health Physics Society.)

Abstract: This whole-body tissue donor to the United States Transuranium and Uranium Registries was occupationally exposed to plutonium nitrate-dioxide mixture via chronic inhalation. This individual was involved in the Manhattan Project operations and later participated in medical follow-up studies. Soft tissues and bones collected at autopsy were analyzed for 238Pu, 239+240Pu, and 241Am. Fifty-three years post-intake, 700±2 Bq of 239+240Pu were still retained in the skeleton, 661±11 Bq in the liver, and 282±3 Bq in the respiratory tract. Bioassay measurements and organ activities at the time of death were used to estimate the intake and radiation doses using the TAURUS internal dosimetry software. For this individual, an ICRP Publication 130 Human Respiratory Tract Model with case-specific particle size of 0.3 μm, ICRP Publication 100 Human Alimentary Tract Model, and ICRP Publication 141 Plutonium Systemic Model adequately described long-term plutonium retention and excretion. The total cumulative 239+240Pu intake of 31,716 Bq was estimated, of which 24,853 Bq (78.4%) were contributed by inhalation of plutonium nitrate and 6,863 Bq (21.6%) of plutonium dioxide. The committed equivalent doses to the red bone marrow, bone surface, liver, lungs, and brain were 0.71 Sv, 6.5 Sv, 8.3 Sv, 3.8 Sv, and 0.068 Sv, respectively. The committed effective dose was 1.22 Sv., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Health Physics Society.)

Abstract: Inhalation of plutonium is a significant contributor of occupational doses in plutonium production, nuclear fuel reprocessing, and cleanup operations. Accurate assessment of the residence time of plutonium in the lungs is important to properly characterize dose and, consequently, the risk from inhalation of plutonium aerosols. This paper discusses the long-term retention of plutonium in different parts of the respiratory tract of two workers who donated their bodies to the US Transuranium and Uranium Registries. The post-mortem tissue radiochemical analysis results, along with the urine bioassay data, were interpreted using Markov Chain Monte Carlo and the latest biokinetic models presented in the Occupational Intakes of Radionuclides series of ICRP publications. The materials inhaled by both workers were found to have solubility between that of plutonium nitrates and oxides. The long-term solubility was also confirmed by comparison of the activity concentration in the lungs and the thoracic lymph nodes. The data from the two individuals can be explained by assuming a bound fraction (fraction of plutonium deposited in the respiratory tract that becomes bound to lung tissue after dissolution) of 1% and 4%, respectively, without having to significantly alter the particle clearance parameters. Effects of different assumptions about the bound fraction on radiation doses to different target regions was also investigated. For inhalation of soluble materials, an assumption of fb of 1%, compared to the ICRP default of 0.2%, increases the dose to the most sensitive target region of the respiratory tract by 258% and that to the total lung by 116%. Some possible alternate methods of explaining higher-than-expected long-term retention of plutonium in the upper respiratory tract of these individuals-such as physical sequestration of material into the scar tissues and possible uptake by lungs-are also briefly discussed., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Health Physics Society.)

NCRP Report 156 describes soluble radionuclide retention kinetics in a wound, segregated into four retention categories: weak (W), moderate (M), strong (S), and avid (A). An alternate single-parameter model, the negative power function, t, is presented in this paper to describe the time behavior of radionuclide retention. With this mathematical description, γ is a single parameter that can be used to assign the wound retention category rapidly. Using the power function description of wound retention, the various wound categories present as straight lines on log scales with different slopes corresponding to the various retention categories. Regression analysis of average retention values in NCRP 156 shows γ = 0.735 ± 0.132, 0.514 ± 0.015, 0.242 ± 0.016, and 0.053 ± 0.023 for the weak, moderate, strong, and avid categories, respectively. A case study is presented (REAC/TS Registry case 1284) where a power function is shown to fit retention data in a Pu/Am hand wound up to 2,000 d (5.4 y) post-accident.

The three principal pathways for intakes of plutonium are ingestion, inhalation, and contaminated wounds. In August 2018, a glovebox worker at Los Alamos National Laboratory (LANL) sustained a puncture from a thread of a braided steel cable contaminated with Pu. The puncture produced no pain, no blood, and little or no visible mark. As a result, the potential for a contaminated wound was not immediately recognized, and a wound count was not conducted until elevated urine bioassay results were received 12 d after the incident. This paper discusses the circumstances of the incident, along with the medical response and dose assessment, and a discussion of the risks and benefits of the medical interventions.

The administration of chelation therapy to treat significant intakes of actinides, such as plutonium, affects the actinide's normal biokinetics. In particular, it enhances the actinide's rate of excretion, such that the standard biokinetic models cannot be applied directly to the chelation-affected bioassay data in order to estimate the intake and assess the radiation dose. The present study proposes a new chelation model that can be applied to the chelation-affected bioassay data after plutonium intake via wound and treatment with DTPA. In the proposed model, chelation is assumed to occur in the blood, liver, and parts of the skeleton. Ten datasets, consisting of measurements of C-DTPA, Pu, and Pu involving humans given radiolabeled DTPA and humans occupationally exposed to plutonium via wound and treated with chelation therapy, were used for model development. The combined dataset consisted of daily and cumulative excretion (urine and feces), wound counts, measurements of excised tissue, blood, and post-mortem tissue analyses of liver and skeleton. The combined data were simultaneously fit using the chelation model linked with a plutonium systemic model, which was linked to an ad hoc wound model. The proposed chelation model was used for dose assessment of the wound cases used in this study.

The urinary excretion and wound retention data collected after a Pu-contaminated wound were analyzed using Markov Chain Monte Carlo (MCMC) to obtain the posterior distribution of the intakes and doses. An empirical approach was used to model the effects of medical treatments (chelation and excision) on the reduction of doses. It was calculated that DTPA enhanced the urinary excretion, on average, by a factor of 17. The empirical analysis also allowed calculation of the efficacies of the medical treatments-excision and chelation averted approximately 76% and 5.5%, respectively, of the doses that would have been if there were no medical treatment. All bioassay data are provided in the appendix for independent analysis and to facilitate the compartmental modeling approaches being developed by the health physics community.

To characterize the health effects of incorporated plutonium, many experiments have been conducted using different animal models. These range from (1) applied (tissue uptake/retention determination, decorporation therapy efficacy), (2) fundamental (gene expression, cancer induction), and (3) dosimetry models. In recent years, the use of animals for scientific purposes has become a public concern. The application of the 3Rs - Replace (use of alternative methods or animals not considered capable of experiencing pain, suffering, and distress), Reduce (reduction in animal numbers), and Refine (better animal welfare and minimization of suffering, pain and distress) - has increased to address ethical concerns and legislative requirements. The introduction of novel non-animal technologies is also an important factor as complementary options to animal experimentation. In radiotoxicology research, it seems there is a natural tendency to Replace given the possibility of data reuse obtained from contamination cases in man and animal studies. The creation of "registries" and "repositories" for nuclear industry workers (civil and military) is now a rich legacy for radiotoxicological measurements. Similarly, Reduction in animal numbers can be achieved by good experimental planning with prior statistical analyses of animal numbers required to obtain robust data. Multiple measurements in the same animal over time (external body counting, excreta collection) with appropriate detection instruments also allow Reduction. In terms of Refinement, this has become "de rigueur" and a necessity given the societal and legal concerns for animal welfare. For research in radiotoxicology, particularly long-term studies, better housing conditions within the constraints of radiation protection issues for research workers are an important concern. These are all pertinent considerations for the 3Rs remit and future research in radiotoxicology.

A registry of plutonium-induced lung fibrosis diagnosed in members of a cohort of the first Russian nuclear industry facility Mayak Production Association was established. The registry includes 188 plutonium-induced lung fibrosis diagnoses: 117 (62.23%) in males and 71 (37.77%) in females. This paper describes the structure and detailed characteristics of the registry. Plutonium-induced lung fibrosis was shown to have no association with cumulative lung absorbed dose from external gamma rays as of the date of diagnosis. On the contrary, the plutonium-induced lung fibrosis rate was shown to be associated with cumulative lung absorbed dose from incorporated alpha particles and to increase significantly with increasing dose from internal radiation exposure. This paper discusses potential applications of the registry to scientific investigations in the future.

The US Transuranium and Uranium Registries is a human tissue program that collects tissues posthumously from former nuclear workers and radiochemically analyzes them for actinides such as plutonium, americium, and uranium. It was established in 1968 with the goal of advancing science and improving the safety of future workers. Roundtable participants recalled various aspects of this multidisciplinary research program, from establishing consistent autopsy protocols to comparing the registries' findings to those of other programs, such as the historical beagle dog studies and the Russian Radiobiological Human Tissue Repository. The importance of meeting ethical and legal requirements, including written consent forms, was emphasized, as was the need to know whether workers were exposed to nonradiological hazards such as beryllium or asbestos. At Rocky Flats, a bioassay program was established to follow workers after they terminated employment. The resulting data continue to help researchers to improve the biokinetic models that are used to estimate intakes and radiation doses. After 50 y, the US Transuranium and Uranium Registries continues to contribute to our understanding of actinides in humans, which is a testament to the vision of its founders, the generosity of its tissue donors, and the many dedicated scientists who have worked together to achieve a common goal.

Internalization of radionuclides occurs not only by inhalation, ingestion, parenteral injection (i.e., administration of radioactive material for a medical purpose), and direct transdermal absorption, but also by contaminated wounds. In June 2010, a glove-box operator at the U.S. Department of Energy's Savannah River Site sustained a puncture wound while venting canisters containing legacy materials contaminated with Pu. To indicate the canisters had been vented, a flag was inserted into the vent hole. The shaft of the flag penetrated the protective gloves worn by the operator. Initial monitoring performed with a zinc-sulfide alpha detector indicated 300 dpm at the wound site. After being cleared by radiological controls personnel, the patient was taken to the site medical facility where decontamination was attempted and diethylenetriaminepentaacetic acid (DTPA) was administered intravenously within 1.5 h of the incident. The patient was then taken to the Savannah River Site In Vivo Counting Facility where the wound was counted with a Canberra GL 2820 high-purity germanium detector, capable of quantifying contamination by detecting low-energy x rays and gamma rays. In addition to the classic 13, 17, and 20 keV photons associated with Pu, the low-yield (0.04%) 43.5 keV peak was also detected. This indicated a level of wound contamination orders of magnitude above the initial estimate of 300 dpm detected with handheld instrumentation. Trace quantities of Am were also identified via the 59.5 keV peak. A 24 h urine sample collection was begun on day 1 and continued at varying intervals for over a year. The patient underwent a punch biopsy at 3 h postincident (14,000 dpm removed) and excisional biopsies on days 1 and 9 (removal of an additional 3,200 dpm and 3,800 dpm, respectively). The initial post-DTPA urine sample analysis report indicated excretion in excess of 24,000 dpm Pu. Wound mapping was performed in an effort to determine migration from the wound site and indicated minimum local migration. In vivo counts were performed on the liver, axillary lymph nodes, supratrochlear lymph nodes, and skeleton to assess uptake and did not indicate measurable activity. Seventy-one total doses of DTPA were administered at varying frequencies for 317 d post intake. After allowing 100 d for removal of DTPA from the body, five 24 h urine samples were collected and analyzed for dose assessment by using the wound model described in National Council on Radiation Protection and Measurements Report No. 156. The total effective dose averted via physical removal of the contaminant and DTPA administration exceeded 1 Sv, demonstrating that rapid recognition of incident magnitude and prompt medical intervention are critical for dose aversion.

After a plutonium-contaminated wound, the role of an internal dosimetrist is to inform the patient and the physician of the dosimetric considerations. The doses averted due to medical treatments (excision or chelation) are higher if the treatments are administered early; therefore, the internal dosimetrist needs to rely on limited information on wound counts and process knowledge for advising the physician. Several wound cases in the literature were reviewed to obtain estimates of the efficacies of surgical excision and chelation treatment after plutonium-contaminated wounds. The dose coefficients calculated by coupling the NCRP 156 wound model with the systemic model were used to derive the decision guidelines that may indicate medical treatment based on 1) the concept of saved doses proposed by the NCRP 156 wound model, 2) the limits recommended by the CEC/DOE guidebook, and 3) the Clinical Decision Guidelines proposed in NCRP Report No. 161. These guidelines by themselves, however, are of limited use for several reasons, including 1) large uncertainties associated with wound measurements, 2) exposure to forms of radionuclides that cannot be assigned to a single category in the NCRP 156 framework, 3) inability of the NCRP 156 model to explain some of the wound cases in the literature, 4) neglect of the local doses to the wound site and the pathophysiological response of the tissue, 5) poorly understood relationship between effective doses and risks of late health effects, and 6) disregard of the psychological aspects of radionuclide intake.

During the aftermath of a radiological accident or attack, the rapid identification of individuals who have internalized medically significant amounts of material is paramount to guide medical and public health decisions. This paper explores the utility of hand-held, pancake GM detectors to determine if an individual has inhaled Sr, Cs, Pu, Pu, or Am in quantities requiring treatment. Additionally, ingestion of Sr or Cs was considered. Both Sr and Cs were modeled in equilibrium with their progeny, but the progeny of Pu, Pu, and Am were excluded. Treatment thresholds are defined using the National Council on Radiation Protection & Measurements' (NCRP) clinical decision guides (CDGs). Using Monte Carlo N-Particle (MCNP) modeling software, a human phantom and detector were modeled to determine the activity required to achieve a detector reading of twice background 1, 7, or 30 d post-ingestion or post-inhalation. Modeling found that inhaled Pu, Pu, and Am are detectable only if the contaminated individual inhaled thousands-fold more material than the CDG. This lack of detectability means that hand-held GM detectors are inappropriate for initial screening for americium or plutonium and that more intensive screening is necessary to confirm suspected contamination. Cesium-137, by contrast, could be detected at levels 10- to 100-fold lower than the amount requiring treatment, allowing quick differentiation between contaminated and uncontaminated individuals. Surprisingly, Sr was detectable within a factor of 2 of the amount requiring treatment. Detection of Sr was due primarily to bremsstrahlung radiation from beta interactions with calcium in bone. While rapid screening could identify individuals contaminated by Cs and possibly with Sr, further screening of identified individuals is necessary to establish medical need. However, these contaminated individuals could still be prioritized for further testing and possible presumptive treatment. Based on the findings of this study, concepts of operation for the use of hand-held survey meters should be developed for the screening of individuals potentially internally contaminated with Cs and Sr.

The NCRP 156 wound model was heavily based on data from animal experiments. The authors of the report acknowledged this limitation and encouraged validation of the models using data from human wound exposures. The objective of this paper was to apply the NCRP 156 wound models to the bioassay data from four plutonium-contaminated wound cases reported in the literature. Because a wide variety of forms of plutonium can be expected at a nuclear facility, a combination of the wound models-rather than a single model-was used to successfully explain both the urinary excretion data and wound retention data in three cases. The data for the fourth case could not be explained by any combination of the default wound models. While this may possibly be attributed to the existence of a category of plutonium whose solubility and chemistry are different than those described by the NCRP 156 default categories, the differences may also be the result of differences in systemic biokinetics. The concept of using a combination of biokinetic models may be extended to inhalation exposures as well, where more than one form of radionuclide-particles of different solubility or different sizes-may exist in a workplace.

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.

Small, highly radioactive fragments of material incorporated into metallic matrices are commonly found at nuclear weapons test and accident sites and can be inhaled by wildlife. Inhaled particles often partition heterogeneously in the lungs, with aggregation occurring in the periphery of the lung, and are tenaciously retained. However, dose rates are typically calculated as if the material were homogeneously distributed throughout the entire organ. Here the authors quantify the variation in dose rates for alpha-, beta-, and gamma-emitting radionuclides with particle sizes from 0.01-150 μm (alpha) and 1-150 μm (beta, gamma) and considering three averaging volumes-the entire lung (64 cm), a 10-cm volume of tissue, and a 1-cm volume of tissue. Dose rates from beta-emitting particles (e.g., Sr) were approximately one order of magnitude higher than those from gamma-emitting radionuclides (e.g., Cs). Self-shielding within the particle, which reduces the dose rate to the surrounding tissue, was negligible for gammas and minor for betas. For alpha-emitting particles (e.g., Pu), self-shielding in larger particles is substantial, with >90% of emissions captured within particles of +20 μm diameter; but for smaller sizes of the respirable range of 0.01 to 5 μm, an average of 85% of the energy escapes the particle and is deposited in the surrounding tissues. These data provide more detail on respirable particles, which may remain lodged deep in the lung where they represent a considerable contribution to long-term lung dose rates. For practical dose rate calculation purposes, a graph of particle size vs. dose rates for plutonium-containing hot particles is provided. This study demonstrates one possible approach to dose assessments for biota in environments contaminated by radioactive particles, which may prove useful for those engaged in environmental radioprotection.

New data from the workers at the Mayak nuclear facility near Chelyabinsk, Russia, apparently show a linear increase in the risk of lung cancer with increasing dose. Furthermore, this increase occurs without a threshold. However, these conclusions are at variance with the results reported by other investigators. A possible cause of these inconsistencies could be the lack of application of microdosimetric considerations when discussing "dose" to the lung.

Comparisons between results of in vivo counting measurements of americium burden and results from radiochemical analyses of organ samples taken at autopsy of 11 cases of former Mayak workers were made. The in vivo counting measurements were performed 3-8 y before death. The best agreement between in vivo counting measurements for americium and autopsy data was observed for the skull. For lungs and liver, the ratios of burden measured by in vivo counting to those obtained from radiochemical analyses data ranged from 0.7-3.8, while those for the skull were from 1.0-1.1. There was a good correlation between the estimates of americium burden in the entire skeleton obtained from in vivo counting with those obtained from autopsy data. Specifically, the skeletal burden ratio, in vivo counting/autopsy, averaged 0.9 ± 0.1. The prior human americium model, D-Am2010, used in vivo counting measurements for americium in the skeleton to estimate the contents of americium and plutonium at death. The results using this model indicate that in vivo counting measurements of the skull can be used to estimate internal doses from americium in the Mayak workers. Additionally, these measurements may also be used to provide a qualitative assessment of internal doses from plutonium.

This paper presents the results of analyses of the incidence of malignant neoplasms in lung, liver, and bone and associated connective tissues among Mayak nuclear workers exposed to both internally incorporated plutonium and to external gamma radiation. The study cohort included 22,373 individuals employed at the reactors and radiochemical and plutonium production facilities of the Mayak nuclear complex during 1948-1982 and followed up to the end of 2004. All analyses were carried out by Poisson regression, and the doses used were derived using a recently available update of organ doses, Mayak doses-2008. There was clear evidence for the linear association between internal plutonium dose and the risk of lung cancer. For males, there was evidence of a significant internal plutonium dose response for all histological types of lung cancer evaluated (adenocarcinoma, squamous-cell, and other epithelial); the estimated excess relative risk (ERR)/Gy for adenocarcinoma was the largest (ERR/Gy = 32.5; 95% CI: 16.3; 71.9), about 11-fold higher than that for squamous-cell lung cancer (ERR/Gy = 3.1; 95% CI: 0.3; 9.1). The relationship between liver cancer risk and plutonium exposure was best described by a linear-quadratic (LQ) function, but the LQ effect was diminished after restricting internal doses <2 Gy. Hepatocellular cancer was the most frequently observed type of liver cancer associated with internal plutonium exposure, and hemangiosarcomas were exclusively observed only at high internal plutonium doses (>4 Gy). For malignant neoplasms of bone and associated connective tissues, the trend was not statistically significant in relation to internal plutonium dose, but a statistically significantly higher risk (RR=13.7; 95% CI= 3.0; 58.5) was found among unmonitored female plutonium workers who were employed in the most hazardous plutonium production facility commissioned prior to 1950.

Ventricular assist devices emerged as a widely used modality for treatment of end-stage heart failure; however, despite significant advances, external energy supply remains a problem contributing to significant patient morbidity and potential mortality. One potential solution is using the nuclear radioisotope Plutonium-238 as a power source. Given its very high energy density and long half-life, Plutonium-238 could eventually allow a totally intracorporeal ventricular assist system that lasts for the patient's lifetime. Risks, such as leakage and theft identified decades ago, still remain. However, it is possible that newer technologies could be used to overcome the system complexity and unreliability of the previous generations of nuclear-powered mechanical assist systems. Were it not for the remaining safety risks, Plutonium-238 would be an ideal energy source for this purpose.

Skin penetration by radionuclide contaminants serves as a route of entry into the body and may pose a serious health risk to humans depending on the magnitude of intake. The United States Transuranium and Uranium Registry whole body Case 0262 was involved in a wound intake of plutonium at the Hanford Site. The registrant died about 33 years later. Results were initially reported in 2007 regarding the deposition and retention of plutonium in various tissues, including the wound site. However in 2009, an additional (previously unrecorded) sample of the wound tissue was located in the National Human Radiobiological Tissue Repository. The new sample was analyzed using inductively coupled plasma-mass spectrometry (ICP-MS), and the results were used to calibrate the measurement of emitted Pu x-rays from the original wound tissue sample made in 2007. In the present study, the analysis of Pu absorption rates from the wound and axillary lymph node from the initial study is repeated using the additional wound activity data and ICP-MS calibration. This new analysis is carried out using the Weighted Likelihood Monte Carlo Sampling (WeLMoS) method and code, which applies Bayesian inference to calculate the posterior probability distribution of intake and wound absorption parameters directly from the observed data and the assumed biokinetic model structure. The resulting central estimates of empirical wound absorption parameters and their associated uncertainties are here compared with the empirical values recommended in NCRP Report No. 156 for plutonium and with the maximum likelihood point estimates derived in the initial study from the Case 0262 data available at the time.

The U.S. Transuranium and Uranium Registries' tissue donors 0202 and 0407 are the two most highly exposed of the 18 registrants who were involved in the 1965 plutonium fire accident at a defense nuclear facility. Material released during the fire was well characterized as "high fired" refractory plutonium dioxide with 0.32-μm mass median diameter. The extensive bioassay data from long-term follow-up of these two cases were used to evaluate the applicability of the Human Respiratory Tract Model presented by International Commission on Radiological Protection in Publication 66 and its revision proposed by Gregoratto et al. in order to account for the observed long-term retention of insoluble material in the lungs. The maximum likelihood method was used to calculate the point estimates of intake and tissue doses and to examine the effect of different lung clearance, blood absorption, and systemic models on the goodness-of-fit and estimated dose values. With appropriate adjustments, Gregoratto et al. particle transport model coupled with the customized blood absorption parameters yielded a credible fit to the bioassay data for both cases and predicted the Case 0202 liver and skeletal activities measured postmortem. PuO2 particles produced by the plutonium fire are extremely insoluble. About 1% of this material is absorbed from the respiratory tract relatively rapidly, at a rate of about 1 to 2 d (half-time about 8 to 16 h). The remainder (99%) is absorbed extremely slowly, at a rate of about 5 × 10(-6) d (half-time about 400 y). When considering this situation, it appears that doses to other body organs are negligible in comparison to those to tissues of the respiratory tract. About 96% of the total committed weighted dose equivalent is contributed by the lungs. Doses absorbed by these workers' lungs were high: 3.2 Gy to AI and 6.5 Gy to LNTH for Case 0202 (18 y post-intake) and 3.2 Gy to AI and 55.5 Gy to LNTH for Case 0407 (43 y post-intake). This evaluation supports the Gregoratto et al. proposed revision to the ICRP 66 model when considering situations of extremely insoluble particles.

Eight of the most severe cases of acute radiation disease (ARS) known to have occurred in humans (as the result of criticality accidents) had survival times less than 120 h (herein defined as "early death"). These accidents were analyzed and are discussed with respect to the specific accident scenarios and the resulting accident-specific, mixed neutron-gamma radiation clinical dose distributions. This analysis concludes that the cardiovascular system appears to be the most critical organ system failure for causing "early death" following approximate total body, mixed gamma-neutron radiation doses greater than 40-50 Gy. The clinical data also suggest that there was definite chest dose dependence in the resulting survival times for these eight workers, who unfortunately suffered profound radiation injury and unusual clinical effects from such high dose radiation exposures. In addition, "toxemic syndrome" is correlated with the irradiation of large volumes of soft tissues. Doses to the hands or legs greater than 80-100 Gy or radiation lung injury also play significant but secondary roles in causing "early death" in accidents delivering chest doses greater than 50 Gy.

An exploratory epidemiological study was conducted for 319 deceased nuclear workers who had intakes of transuranic radionuclides and histories of employment during the time period from 1943 to 1995. The workers were employed at various facilities throughout the United States, including the Department of Energy defense facilities and uranium mining and milling sites. The majority of individuals were involved in documented radiological incidents during their careers. All had voluntarily agreed to donate their organs or whole body to the United States Transuranium and Uranium Registries. External and internal dose assessments were performed using occupational exposure histories and postmortem concentrations of transuranic radionuclides in critical organs. Statistical data analyses were performed to investigate the potential relationship between radiation exposure and causes of death within this population due to cancers of the lungs, liver, and all sites combined while controlling for the effects of other confounders. No association was found between radiation exposure and death due to cancer (α = 0.05). However, statistically significant associations were found between death due to any type of cancer and smoking (yes or no) (odds ratio = 5.41; 95% CI: 1.42 to 20.67) and rate of cigarette smoking (packs per day) (odds ratio = 2.70; 95% CI: 1.37 to 5.30).

The particle size and quantity of a plutonium dioxide surrogate escaping an open front hood during routine work was measured. Aerosols were collected using a cascade impactor, and the amount of surrogate on each stage of the impactor was measured using neutron activation analysis. The aerodynamic mass median diameter of particles in the breathing zone of a worker was found to be 0.35 ± 5.1 μm. During a 2-h period when normal work activities were mimicked, an average of 3% of the material or 11.13 ± 0.54 μg escaped the hood. This was calculated to be equivalent to 10,000 ± 487 Bq (²³⁹Pu). The activity in the breathing zone of the worker is estimated, based on other research, to be 36 times less than this, or approximately 280 Bq. Worker occupancy factors were considered and a committed effective dose equivalent of 5 mSv was calculated. The cost-benefit analysis showed the use of the open front hood as a reasonable protective measure. Although worker exposure may approach the International Commission on Radiological Protection limit, the cost of the ergonomic injuries caused by work in a glove box is 5,000 times greater than the dose received by the worker. Protective measures such as respiratory protection should be evaluated on a case by case basis to keep worker exposure as low as reasonably achievable.

A 1985 plutonium puncture wound resulted in the initial deposition of 48 kBq of transuranic alpha activity, primarily 239+240Pu and 241Am, in a worker's right index finger. Surgical excisions in the week following reduced the long-term residual wound activity to 5.4 kBq, and 164 DTPA chelation therapy administrations over 17 mo resulted in urinary excretion of about 7 kBq. The case was published in 1988, but now 24 y of follow-up data are available. Annual bioassays have included in-vivo measurements of 241Am in the wound, skeleton, liver, lung, and axillary lymph nodes, and urinalyses for plutonium and 241Am. These measurements have shown relatively stable levels of 241Am at the wound site, with gradually increasing amounts of 241Am detected in the skeleton. Liver measurements have shown erratic detection of 241Am, and the lung measurements indicate Am but as interference from activity in the axillary lymph nodes and skeleton rather than activity in the lung. Urine excretion of Pu since termination of chelation therapy has typically ranged from 10 to 20 mBq d, with Am excretion about 10% of that for 239+240Pu. Annual routine medical exams have not identified any adverse health effects associated with the intake.

The aim of the study was to investigate hematopoietic injury and recovery in residents of the Techa riverside villages who had been chronically exposed to radiation as a result of the activities of the Mayak Nuclear Facility, and evaluate late effects from chronic, low-dose radiation exposures. Whole blood samples were drawn from 338 unexposed individuals resident in noncontaminated villages, and 692 individuals chronically exposed externally (to primarily gamma radiation) and internally from Sr since 1949 at decreasing dose-rates which have currently reached the background levels. The mean cumulative dose in the exposed cohort was 0.62 Gy over the years 1949 to 2008 using the Techa River Dosimetry System (TRDS) 2000. The frequency of chromosome aberrations and mutations in peripheral lymphocytes, and other aspects indicative of cellular and molecular repair of radiation damage, were measured. The subjects were divided into two study groups: (a) 171 individuals who during the early exposure period (where the highest dose-rates were prevalent) were noted to manifest leucopenia and/or were diagnosed with chronic radiation syndrome (CRS), and (b) 521 exposed individuals without cytopenia and CRS. The first group demonstrated an increased frequency of micronuclei, dicentric chromosomes, somatic mutations (CD3-CD4+cells) in lymphocytes, and mutations in the TP53 gene. In addition, they demonstrated a lower Cu/Zn-SOD concentration, a significantly increased concentration of nitric oxide, and a greater apoptotic frequency in peripheral blood lymphocytes compared to exposed individuals without leucopenia. Similar to the unexposed individuals, the second group demonstrated "background levels" of mutational frequencies several years after their exposures, but they did show an increased number of cells with delayed cell cycles based on Chk-2 concentrations compared to the unexposed population. The data are consistent with the idea that a chronic radiation exposure within a dose range from 0.01 Gy to 1.96 Gy results in more severe late hematopoietic effects in a select cohort of highly radiosensitive individuals, rather than an overall increase in late effects in cells of each exposed individual. The authors state that radiation-exposed subjects demonstrating CRS showed an activation of barrier anti-oxidative stress mechanisms at late periods after radiation exposure, apparently in response to a more severe radiation damage than subjects exposed to similar radiation doses but not demonstrating CRS. Finally, the persistence of chromosome aberrations and somatic mutations in the CRS cohort is indicative of an exhaustion of the anti-oxidative stress mechanisms responding for so many years after the exposure, leading to genomic instability.

The major goal of this study is to investigate and quantitatively describe the nature of the relationship between the characteristics of chronic exposure to ionizing radiation and specific patterns of hematopoiesis reduction. The study is based on about 3,200 hemograms taken for inhabitants of the Techa riverside villages over the years 1951-1956, i.e., the period characterized by a gradual decrease in dose rates. The mean cumulative red bone marrow dose was 333.6 + or - 4.6 mGy. The approach to statistical analyses involved both empirical methods and modeling (generalized linear models and logistic regressions). The results of the analyses highlighted a gradual increase in the frequency of cytopenias with dose rate. The impact of exposure on hematopoiesis reduction patterns was found to be more substantial than that of age and health status. Dose rates resulting in a two-fold increase in the frequency of cytopenias have been estimated.

Previous studies of cancer incidence among persons living in municipalities within one mile of two nuclear materials processing and fabrication plants in Pennsylvania were extended for the years 1998-2004. It had been shown that mailing addresses for residents of rural areas often did not reflect the actual municipality of residence and, if not corrected, would bias study results. The previous studies had corrected for this bias. Accordingly for the extended study, we obtained mailing addresses from the Pennsylvania Department of Health (PDH) for 866 persons with cancer who presumably lived in one of eight minor civil divisions (MCDs) near or encompassing the former nuclear facilities, designated as Area 1 in previous studies conducted by the PDH. Street addresses were geocoded and local postmasters were asked to place rural delivery addresses, post office boxes and street addresses that could not be geocoded into the correct MCD of actual residence. Over 15% of the mailing addresses were found not to be within the boundaries of the Area 1 municipalities. After the mailing addresses of individuals with cancer were placed in their proper MCD of residence, the number of persons diagnosed with cancer (n = 708) and confirmed to have lived in Area 1 was as expected (728.4) based on cancer incidence rates in the general population of Pennsylvania (SIR 0.97; 95% CI 0.90-1.05). To further evaluate the patterns of cancer rates near these nuclear facilities and the influence of improved reporting and geocoding of addresses over time, analyses were conducted of publicly available cancer incidence data from 1990 through 2004. Based on mailing addresses, a steady decrease in the number of cancers reported in the Area 1 proximal MCDs was seen, in contrast to a steady rise in the number of cancers reported in seven adjacent but more distant MCDs from the nuclear facilities, designated as Area 2. These patterns were attributed to improvements over time in the geocoding of residential mailing addresses coupled with the gradual elimination and replacement of rural delivery addresses with street addresses. The incorrect placement of mailing addresses in residential Area 1 municipalities prior to about 2002 overestimated the number of cancers occurring among residents living in close proximity to the nuclear facilities and, correspondingly, underestimated the number among Area 2 residents. Summing Area 1 and Area 2 data showed that there was no change in cancer rates over time. These results are consistent with previous studies indicating that living in municipalities near the former Apollo-Parks nuclear facilities was not associated with an increase in cancer occurrence.

Risk estimates for deterministic effects of inhaled weapons-grade plutonium (WG Pu) are needed to evaluate potential serious harm to (1) U.S. Department of Energy nuclear workers from accidental or other work-place releases of WG Pu; and (2) the public from terrorist actions resulting in the release of WG Pu to the environment. Deterministic health effects (the most serious radiobiological consequences to humans) can arise when large amounts of WG Pu are taken into the body. Inhalation is considered the most likely route of intake during work-place accidents or during a nuclear terrorism incident releasing WG Pu to the environment. Our current knowledge about radiation-related harm is insufficient for generating precise estimates of risk for a given WG Pu exposure scenario. This relates largely to uncertainties associated with currently available risk and dosimetry models. Thus, rather than generating point estimates of risk, distributions that account for variability/uncertainty are needed to properly characterize potential harm to humans from a given WG Pu exposure scenario. In this manuscript, we generate and summarize risk distributions for deterministic radiation effects in the lungs of nuclear workers from inhaled WG Pu particles (standard isotopic mix). These distributions were developed using NUREG/CR-4214 risk models and time-dependent, dose conversion factor data based on Publication 30 of the International Commission on Radiological Protection. Dose conversion factors based on ICRP Publication 30 are more relevant to deterministic effects than are the dose conversion factors based on ICRP Publication 66, which relate to targets for stochastic effects. Risk distributions that account for NUREG/CR-4214 parameter and model uncertainties were generated using the Monte Carlo method. Risks were evaluated for both lethality (from radiation pneumonitis) and morbidity (due to radiation-induced respiratory dysfunction) and were found to depend strongly on absorbed-dose-rate history (which depends on WG Pu solubility). The results obtained were compared to new data from animal and epidemiological studies. Our findings suggest that NUREG/CR-4214 models for assessing lethality risk from inhaled radionuclides may need some modest revision in light the new data. However, for assessing morbidity risks, major revisions may be needed.

For radiation-related cancer risk evaluation, it is important to assess not only influences of individual risk factors but also their interactive effects (e.g., additive, multiplicative, etc.). Multivariate analysis methods adapted for interactive effects allow such assessments. We have used a multivariate analysis approach to investigate the pair-wise interactions of the previously identified three main etiological factors for lung cancer induction in Russian workers of the Mayak Production Association (PA) nuclear enterprise. These three factors are as follows: (1) body burden of inhaled plutonium-239 (239Pu), an influence on absorbed alpha-radiation dose; (2) cumulative, absorbed external gamma-radiation dose to the lung; and (3) level of cigarette smoking as indicated by a smoking index (SI). The SI represents the cigarettes smoked per day times years smoking. The Mayak PA workers were exposed by inhalation to both soluble and insoluble forms of 239Pu. Based on a cohort of 4,390 persons (77% male), we conducted a nested, case-control study of lung cancer induction using 486 matched cases and controls. Each case was matched to two controls. Matching was based on five factors: sex, year of birth, year work began, profession, and workplace. Three levels of smoking were considered: low (SI = 1 to 499), used as a reference level; middle (SI = 500 to 900); and high (SI = 901 to 2,000). For lung cancer induction, a supra-multiplicative effect was demonstrated for high external gamma-ray doses (> 2.0 Gy) plus high 239Pu intakes (body burden >2.3 kBq). This observation is consistent with the hypothesis of curvilinear dose-response relationships for lung cancer induction by high- and low-LET radiations. The interaction between radiation (external gamma rays or 239Pu body burden) and cigarette smoke was found to depend on the smoking level. For the middle level of smoking in combination with gamma radiation (> 2.0 Gy) or 239Pu body burden (> 2.3 kBq), results were consistent with additive effects. However, for the high level of smoking in combination with gamma radiation (> 2.0 Gy) or 239Pu body burden (> 2.3 kBq), results were consistent with the occurrence of multiplicative effects. These results indicate that low-dose risk estimates for radiation-induced lung cancer derived without adjusting for the influence of cigarette smoking could be greatly overestimated. Further, such systematic error may considerably distort the shape of the risk vs. dose curve and could possibly obscure the presence of a dose threshold for radiation-induced lung cancer.

A model was developed to calculate ambient air concentrations, surface deposition, and lifetime carcinogenic risk with uncertainty from plutonium released to the air from the Rocky Flats Plant between the years 1953 and 1989. The model integrated airborne release estimates and atmospheric dispersion and deposition calculations from 37 years of routine plant operations and episodic releases. Episodic releases included two major fires in 1957 and 1969 that breached the building air filtration systems, and suspension of plutonium contaminated soil from the former 903 waste storage area during high winds. Predicted air concentrations included contributions from site releases and resuspension from contaminated soil. Inhalation was the only exposure pathway considered. Environmental measurements suitable for model validation were lacking for the period when major site releases occurred (1953 to 1970). However, environmental media, such as soil and lake sediment, are natural accumulators and provided evidence of past offsite releases. The geometric mean predicted-to-observed (P/O) ratio for soil was 0.93 with a geometric standard deviation of 1.6. The model systematically underpredicted concentrations near the 903 Area because large, nonrespirable particles that deposited close to the source were not included in release estimates. Plutonium soil inventories for the model domain had P/O ratios ranging from 0.22 to 4.2. The geometric mean P/O ratio for ambient air was 0.90 with a geometric standard deviation of 2.6. Age-dated sediment cores from Standley Lake had a geometric mean P/O ratio of 1.0 with a geometric standard deviation of 1.7. Predicted-to-observed ratios for plutonium inventories in Great Western Reservoir ranged from 0.36 to 1.7. Lifetime cancer incidence risks were calculated for a male laborer scenario who resided in the model domain for the entire assessment time. Maximum cancer risks ranged from 10-6 (5th percentile) to 10(-4) (95th percentile). Most of the exposure was incurred during the 1950's.

The risk per unit dose to the four primary cancer sites for plutonium inhalation exposure (lung, liver, bone, bone marrow) is estimated by combining the risk estimates that are derived from four independent approaches. Each approach represents a fundamentally different source of data from which plutonium risk estimates can be derived. These are: (1) epidemiologic studies of workers exposed to plutonium; (2) epidemiologic studies of persons exposed to low-LET radiation combined with a factor for the relative biological effectiveness (RBE) of plutonium alpha particles appropriate for each cancer site of concern; (3) epidemiologic studies of persons exposed to alpha-emitting radionuclides other than plutonium; and (4) controlled studies of animals exposed to plutonium and other alpha-emitting radionuclides extrapolated to humans. This procedure yielded the following organ-specific estimates of the distribution of mortality risk per unit dose from exposure to plutonium expressed as the median estimate with the 5th to 95th percentiles of the distribution in parentheses: lung 0.13 Gy(-1) (0.022-0.53 Gy(-1)); liver 0.057 Gy(-1) (0.011-0.47 Gy(-1)); bone 0.0013 Gy(-1) (0.000060-0.025 Gy(-1)); bone marrow (leukemia), 0.013 Gy(-1) (0.00061-0.05 Gy(-1)). Because the different tissues do not receive the same dose following an inhalation exposure, the mortality risk per unit intake of activity via inhalation of a 1-microm AMAD plutonium aerosol also was determined. To do this, inhalation dose coefficients based on the most recent ICRP models and accounting for input parameter uncertainties were combined with the risk coefficients described above. The following estimates of the distribution of mortality risk per unit intake were determined for a 1-microm AMAD plutonium aerosol with a geometric standard deviation of 2.5: lung 5.3 x 10(-7) Bq(-1) (0.65-35 x 10(-7) Bq(-1)), liver 1.2 x 10(-7) Bq(-1) (0.091-20 x 10(-7) Bq(-1)), bone 0.11 x 10(-7) Bq(-1) (0.0030-4.3 x 10(-7) Bq(-1)), bone marrow (leukemia) 0.049 x 10(-7) Bq(-1) (0.0017-0.59 x 10(-7) Bq(-1)). The cancer mortality risk for all sites was estimated to be 10 x 10(-7) Bq(-1) (2.1-55 x 10(-7) Bq(-1))--a result that agrees very well with other recent estimates. The large uncertainties in the risks per unit intake of activity reflect the combined uncertainty in the dose and risk coefficients.

The United States Department of Energy Pantex Plant quality evaluation program for plutonium pits is an extensive program that includes 1) weigh and leak check system; 2) radiography; and 3) dye penetrant testing. Successful completion of these diagnostics qualifies a pit to remain in the active status stockpile program. The use of lead aprons and a robot when handling the plutonium pits minimizes personnel exposures to ionizing radiation. All personnel exposures to ionizing radiation at Pantex Plant are As Low As Reasonably Achievable.

Investigation of a possible increase in sensitivity to occurrence of radionuclide-induced skeletal malignancy with increasing body size was analyzed among 358 beagles injected as young adults with either 226Ra or monomeric 239Pu and maintained for their lifespans. Corresponding analyses were performed for about 240 other beagles injected as young adults with 90Sr, 228Ra, or 228Th. Body masses at the time of injection ranged between about 5.6 and 16 kg. Logistic regression analysis using body mass and cumulative skeletal radiation dose as the independent variables indicated that there could not be established a dependency of tumor occurrence upon body mass, although skeletal dose was found to be significantly correlated with occurrence of bone cancer. Regression analysis indicated that for any dosage group there could not be established a correlation between body mass and skeletal dose. Each dosage group having similar injected kBq kg(-1) for each nuclide was divided into 2 subgroups of equal size, one containing the less massive dogs and the other containing the more massive dogs. These subgroups within a roughly uniform value of skeletal dose-rate were compared by Fisher's Exact Test, and the less massive subgroups were combined within each nuclide for an additional, separate analysis against the combined more massive subgroups using the same method. In only one instance (the dosage group given 3607 kBq 90Sr kg(-1)) was there indicated a substantially greater tumor occurrence among dogs in the more massive subgroup (p = 0.061). However, for the group given 0.382 kBq 239Pu kg(-1) there was indicated a significant difference between subgroups, but the effect was exactly opposite to that found for the highest level 90Sr dogs in that the less massive subgroup had a higher relative tumor occurrence than the most massive (p = 0.042). For all groups with a p-value < 0.10, a possible correlation was investigated between survival and body mass at injection (since bone tumor occurrence might be a function of longevity), but a significant relationship could not be determined. No significant differences could be established between the combined more massive and the combined less massive subgroups for any radionuclide. We conclude that, for the conditions in our experiment, relative size within a species does not contribute importantly to the sensitivity (lifetime occurrence) for induction of skeletal malignancy.

Project 2.3 of the Joint Coordinating Committee on Radiation Effects Research (JCCRER) is a study of deterministic health effects among a cohort of Russia nuclear workers. The preliminary study population includes a stratified random sample of 221 radiation workers who were employed in a cohort of 8,055 workers at the Mayak PA facilities for at least one year during the period from 1948 to 1958. High annual doses, approaching 1 Gy per year from external and internal radiation sources, were reported for a significant proportion of the workers in this cohort. The present data set includes 96 cases of chronic radiation sickness (CRS), 14 cases of acute radiation syndrome (ARS) and 13 cases of plutonium pneumosclerosis (PPn). The remainder of the sample consists of "uninjured workers" who had no known history of radiation illness or injury; however, the uninjured workers are not "controls" for radiation exposure. The data base is currently being expanded to 600 individuals sampled from the cohort of workers from 1948 to 1958 to allow a more complete analysis of the deterministic health effects and comparisons with existing health effect models. The final data base will be used with state-of-the-art modeling techniques to determine threshold doses and dose-response relationships for key clinical diagnostic variables.

Available medical records of plutonium injectees exposed in experimental studies of plutonium biokinetics under Manhattan Engineer District auspices have been reviewed for subsequent medical findings potentially related to the plutonium exposures. Five subjects who had been injected with approximately 11 kBq 239Pu, and one injected with 3.5 kBq 238Pu, had useful follow-up medical data. Bone lesions dominated the findings: none of six subjects with follow-up for bone conditions lacked bone lesions clearly or potentially caused, or worsened, by plutonium. Roentgenograms of three subjects, read by a radiologist experienced reading films of radium cases, demonstrated possible to likely plutonium effects. Two cases of osteoporosis or non-specific degenerative changes were seen, associated with a hip fracture and vertebral fractures. Areas of increased bone density were seen, as well as numerous dystopic calcifications and one unusual case of widespread pathologic calcification on bone surfaces probably due to a plutonium-related calciphylactic reaction. Non-skeletal findings include labyrinthitis with inflammatory mastoid changes, conduction deafness, and a benign neurofibroma directly adjacent to bone. The radium literature contains similar observed findings, but interpretation of these limited clinical observations is hampered by lack of quantitative data on humans exposed to radium with respect to prevalence of non-specific ear, mastoid, and skeletal symptomatologies or x-ray findings, or cumulative incidence rates of bone fractures or of other physical disabilities related to ear, mastoid, or bone damage. Disability and invalidism late in life can be risk factors for earlier mortality.

The United States Transuranium and Uranium Registries (USTUR) is a unique postmortem research study of the biokinetics, dosimetry, and possible biological effects of actinide elements in persons with occupational exposure to these radioelements. Evaluation of the causes of death in the admittedly biased self-selected cohort of the first 260 deceased participants in the USTUR revealed, in general, no apparently elevated causes of death except for six cases of mesothelioma and six cases of astrocytoma glioblastoma multiforme. The mesothelioma cases had a documented occupational exposure to asbestos, and the six brain tumor deaths all occurred at a single work site and were not radiation related but rather are likely attributable to a factor specific to the work site or surrounding area. Incidental findings in this cohort did not suggest any radiation related illness or cause of death.

A cohort mortality study was conducted of 15,727 white men employed by the Los Alamos National Laboratory, a nuclear research and development facility. Some of the workers at this facility have been exposed to various forms of ionizing radiation and other potentially hazardous materials. These analyses focused on whole-body ionizing radiation exposures and internal depositions of plutonium. The results indicated that overall mortality among this cohort is quite low, even after nearly 30 y of follow-up. No cause of death was significantly elevated among plutonium-exposed workers when compared with their unexposed coworkers; however, a rate ratio for lung cancer of 1.78 (95% CI = 0.79-3.99) was observed. A case of osteogenic sarcoma, a type of cancer related to plutonium exposure in animal studies, was also observed. Dose-response relationships for whole-body dose from external ionizing radiation and tritium were observed for cancers of the brain/central nervous system, the esophagus, and Hodgkin's disease.

Pacific Northwest Laboratory performed a study to evaluate the consistency of internal dosimetry assessments. A total of eleven laboratories, including DOE sites and NRC licensees, participated in this intercomparison study. Participants were asked to respond to five actual exposure scenarios, previously used in a similar European study. The participating dosimetrists assessed the data of the test scenarios and calculated results in terms of estimated radionuclide intake and the resulting internal doses. To maintain confidentiality, results are given without identifying any site. Except for one scenario, the results showed that the standard deviation of the final results on committed effective dose equivalent for each exposure scenario was about 30-50% of the mean value, giving a consistency slightly greater variant than that of the European study. The discrepancies can be attributed to variations in 1) the interpretation and statistical treatment of the bioassay data; 2) the biokinetic models applied; and 3) the computational tools used. This represents a preliminary study; further intercomparison testing is needed to fully evaluate the problem of dose-assessment inconsistency.

The distribution of skeletal malignancies among our beagles injected with 239Pu as young adults roughly seems to follow the distribution of skeletal mass and skeletal 239Pu. These findings are similar to those we reported previously for a group of dogs given 26Ra. Although there were differences in tumor distribution between the animals given 226Ra and those given 239Pu, most of them were not statistically significant; however, the radium dogs seemed to show a greater sensitivity to bone tumor origin in the tibia, while there may have been a tendency among the plutonium dogs toward increased relative sensitivity in the scapula, lumbar vertebrae, sacrum, and ribs. In contrast, the most common site for the formation of naturally-occurring bone malignancy in the dog is the distal radius. Perhaps there were too few tumors and too few dogs to establish statistical significance. A correlation between tumor location and at least two anatomical-physiological factors in the skeleton indicated that these two factors (site-specific bone turnover rate and percent of red marrow at the site, which is correlated with vascularity) may influence the appearance of malignancies both individually and in combination. Except for the femur, there appeared to be no difference between the relative distribution of skeletal malignancies of low-level (30 Bq-2 Bq kg-1 injected) and high-level (3-122 kBq kg-1) dogs. Distribution of bone tumors between the axial and appendicular skeleton was 50% vs. 50% for 239Pu (42 and 42), but it was 39% axial vs. 61% appendicular (22 and 35, respectively) for dogs given 226Ra. This difference was not significant (p > 0.2).

Retrospective and prospective epidemiologic studies are being conducted as part of a national survey of plutonium workers at four Department of Energy facilities (Los Alamos, NM; Rocky Flats, CO; Mound Laboratory, OH; and Savannah River, SC). A preliminary analysis of mortality was done for all white males who have worked at the Rocky Flats Plant during the period 1952-79. The 452 observed deaths were significantly fewer than the 831 expected for all causes. The 107 deaths due to all malignant neoplasms were also significantly fewer than the 167 expected from these diseases. Expected deaths were derived from age and calendar-specific death rates for U.S. white males. Deaths reported for benign and unspecified neoplasms numbered eight versus an expected two, a significant elevation. These tumors, all intracranial, are the subject of a case-control study to be reported later. Subdividing the cohort on the basis of plutonium exposures and external radiation exposures results in similar overall findings. The benign and unspecified neoplasms, however, were not significantly high in the plutonium-exposed group.