Cumulative Lung Dose Research Articles

An Epidemiological Study of Lung Cancer and Selected Other Cancers among Namibian Uranium Workers.

The Rössing Uranium Limited (RUL) open-cast uranium mine in Namibia has operated since 1976. Studies of underground uranium miners from Europe and North America have shown increased cancer risks (principally lung cancer). We explored the association between radiation doses and selected cancers in RUL mineworkers. Employees with at least one-year of continuous employment between 1976 and 2010 were included. Incident cancer cases [lung, extra-thoracic airways (ETA), leukemia, brain and kidney] occurring before the end of 2015 were identified from the Namibian and South African National Cancer Registries, and RUL's occupational health provider. Using a case-cohort design, data on exposure and confounding factors were collected for all cancer cases among the study cohort and a stratified random sample (sub-cohort) of the cohort, including cases. Radiation doses were estimated based on annual dose records held by RUL. In total, 76 cancer cases (32 lung, 18 ETA, 8 leukemia, 9 brain, 9 kidney) and a sub-cohort of 1,121 sampled from 7,901 RUL employees were included. A weighted Cox model, adjusted for available known confounders, produced a rate ratio (95% CI) for lung cancer of 1.42 (0.42, 4.77) and 1.22 (0.26, 5.68), respectively, for medium and higher cumulative lung dose categories compared to the lower category, and 1.04 (0.95, 1.13) for a dose increase of 10 mSv. This study faced considerable challenges with respect to case ascertainment, exposure estimates, and ensuring accuracy of key variables. Persuasive consistent evidence for elevated cancer risk was not found for radiation or other exposures studied at the Rössing uranium mine.

Repeat Evaluation of Lung Shunt Fraction is Unnecessary: A Retrospective Observational Study of Successive Lung Shunt Fractions from Variable Arterial Distributions in Patients Undergoing Radioembolization of Primary and Secondary Liver Tumors

PurposeTo evaluate whether the recalculation of lung shunt fraction (LSF) is necessary prior to next-stage or same lobe repeat radioembolization. Materials and MethodsRetrospective chart review was performed for patients who underwent radioembolization between February 2008 and December 2018. Eighty of 312 patients had repeat mapping angiograms and LSF calculations. A total of 160 LSF calculations were made using planar imaging (155, [97%]) and single-photon emission computed tomography (5 [3%]) technetium-99m macroaggregated albumin hepatic arterial injection imaging. The mean patient age was 61.8 years ± 12.7; 69 (86%) patients had metastatic disease and 11 (14%) had hepatocellular carcinoma. ResultsPatients had a median LSF of 5% (interquartile range [IQR] 3%–9%) with a median absolute difference of 1.25 (IQR 0.65–3.4) and a median of 76 days (IQR 42.5–120 days) between repeat LSF calculations. There was a median change in LSF of 0.2% between mapping studies (P = .11). There was no statistical significance between the repeat LSFs regardless of the arterial distribution (P = .79) or between tumor types (P = .75). No patients exceeded lung dose limits using actual or predicted prescribed dose amounts. The actual median lung dose was 2.6 Gy (IQR 1.8–4.4 Gy, maximum = 20.5) for the first radioembolization and 2.0 Gy (IQR 1.3–3.7 Gy, maximum = 10.1) for the second radioembolization. ConclusionsNo significant difference in LSF was identified between different time points and arterial distributions within the same patient undergoing repeat radioembolization. In patients who receive well under 30-Gy lung dose for the initial treatment and a 50-Gy cumulative lung dose, repeat radioembolization treatments in the same patient may not require a repeat LSF calculation.

Monte Carlo 90Y PET/CT dosimetry of unexpected focal radiation-induced lung damage after hepatic radioembolisation

Transarterial radioembolization (TARE) with 90Y-loaded microspheres is an established therapeutic option for inoperable hepatic tumors. Increasing knowledge regarding TARE hepatic dose-response and dose-toxicity correlation is available but few studies have investigated dose-toxicity correlation in extra-hepatic tissues. We investigated absorbed dose levels for the appearance of focal lung damage in a case of off-target deposition of 90Y microspheres and compared them with the corresponding thresholds recommended to avoiding radiation induced lung injury following TARE. A 64-year-old male patient received 1.6 GBq of 90Y-labelled glass microspheres for an inoperable left lobe hepatocellular carcinoma. A focal off-target accumulation of radiolabeled microspheres was detected in the left lung upper lobe at the post-treatment 90Y-PET/CT, corresponding to a radiation-induced inflammatory lung lesion at the 3-months 18F-FDG PET/CT follow-up. 90Y-PET/CT data were used as input for Monte-Carlo based absorbed dose estimations. Dose-volume-histograms were computed to characterize the heterogeneity of absorbed dose distribution. The dose level associated with the appearance of lung tissue damage was estimated as the median absorbed dose measured at the edge of the inflammatory nodule. To account for respiratory movements and possible inaccuracy of image co-registration, three different methods were evaluated to define the irradiated off-target volume. Monte Carlo-derived absorbed dose distribution showed a highly heterogeneous absorbed dose pattern at the site of incidental microsphere deposition (volume = 2.13 ml) with a maximum dose of 630 Gy. Absorbed dose levels ranging from 119 Gy to 133 Gy, were estimated at the edge of the inflammatory nodule, depending on the procedure used to define the target volume. This report describes an original Monte Carlo based patient-specific dosimetry methodology for the study of the radiation-induced damage in a focal lung lesion after TARE. In our patient, radiation-induced focal lung damage occurred at significantly higher absorbed doses than those considered for single administration or cumulative lung dose delivered during TARE.

Repeat Thoracic Stereotactic Body Radiation Therapy (SBRT) for Nonsmall Cell Lung Cancer: Long-Term Outcomes, Toxicity, and Dosimetric Considerations

PurposeLung reirradiation for nonsmall cell lung cancer (NSCLC) is common for either recurrent disease or new primary cancer. Dose volume tolerance of the lung after multiple courses of radiation therapy (RT) is unknown. We review our experience with lung reirradiation for patients with NSCLC in a single community setting using stereotactic body radiation therapy (SBRT) to report lung cumulative doses, survival, and toxicity. Methods and MaterialsForty-four patients who received at least 2 curative courses of lung RT with the second course delivered between January 2012 and December 2017 were eligible. All patients had NSCLC and were treated with SBRT for reirradiation. Cumulative lung dose volume histograms for all courses were generated, summated, and converted into cumulative equivalent dose in 2 Gy fractions (EQD2). Actuarial overall survival (OS), local control, and toxicity is reported, including a subset of patients who received more than 2 courses of SBRT. ResultsMedian age of the group was 71 years (range, 51-87). Median survival of the entire group from diagnosis, first, and second courses of RT was 3.94, 3.03, and 2.03 years. Three-year actuarial OS for the entire group was 34.1% from second course of RT. The mean EQD2 Gy3 mean lung dose for all courses was 12.35 Gy (range, 2.7-26.52). The mean EQD2 Gy3 V5Gy, V10Gy, V20Gy, V30Gy, and V40Gy were 40.9%, 25.5%, 14.7%, 10.2%, and 7.7%. Six-year actuarial freedom from grade ≥3 complications was 86.3%. The rate of grade ≥3 lung toxicity was 4.5% (2 of 44). Other late toxicities included grade 3 recurrent laryngeal nerve damage (n = 1) and grade 3 chest wall pain/rib fracture (n = 1). Overall, 32% of patients had more than 2 courses of RT to the lung (range, 3-7). ConclusionsLong-term OS is possible with multiple RT courses to the lung for NSCLC with low toxicity.

Mesothelioma mortality within two radiation monitored occupational cohorts

Purpose The risk of mesothelioma, including cancers of the pleura and peritoneum, was examined within two large cohorts of workers monitored for exposure to ionizing radiation. Methods and materials Mortality was assessed among 253,632 workers routinely monitored for external radiation, including 30,724 industrial radiographers (IR) at shipyards, 142,583 workers at nuclear power plants (NPP), and 83,441 IR who had not worked at an NPP or shipyard. Follow-up was from 1969 through 2011. Standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) were computed; observed numbers of deaths from mesothelioma (including cancers of the pleura and peritoneum) and asbestosis were compared with numbers expected based on age-, sex-, and calendar year-specific national mortality rates. Job history and quantitative asbestos exposure data were unavailable, but work at a shipyard was taken as a surrogate for the likelihood of exposure. Cox proportional hazards models were used to estimate hazard ratios (HRs) for mesothelioma in relation to estimated cumulative radiation exposure to the lung. Results The mean duration of follow-up was 25.3 years (max 42 years). The mean cumulative lung dose was 28.6 mGy (7.3% > 250 mGy). Nearly 20% of the workers had died by 2011. A total of 421 mesothelioma deaths were found (75% occurring after 1999) with increased SMRs among workers monitored in shipyards (SMR 9.97; 95% CI 8.50–11.63) and for NPP workers (SMR 5.55; 95% CI 4.88–6.29), but not for IR who had not worked in shipyards (SMR 1.15; 95% CI 0.53–2.19). Likewise, deaths from asbestosis (n = 189) were also increased for shipyard and NPP workers (SMR = 18.1 and 9.2, respectively), but not among workers who never worked at a shipyard or NPP (SMR = 0.70; n = 1). Radiation dose to the lung was not associated with a statistically meaningful dose-response trend for mesothelioma in the combined cohorts (HR at 100 mGy = 1.10; 95% CI 0.96–1.27; p = .18), nor was mesothelioma risk associated with radiation exposure among IR who had not worked in a shipyard and assumed minimally exposed to asbestos. Conclusions An elevated rate of death from mesothelioma was observed in two radiation-exposed occupational groups with potential for asbestos exposure. The increased risk of death from asbestosis, combined with little evidence of a rising trend in mesothelioma mortality with increasing radiation exposure, suggests that the mesothelioma (and asbestosis) excess in these workers was due to asbestos exposure in shipyards and power plants and not to occupational low-dose radiation.

Incidence of Radiation Pneumonitis After Multiple Courses of Stereotactic Body Radiation Therapy for Lung Cancer Patients

Stereotactic body radiation therapy (SBRT) is a widely used therapy for primary and metastatic lung cancers. Radiation pneumonitis (RP) is one of the most important and potentially serious complications of SBRT, and recent studies have established the clinical and dosimetric risk factors for the development of RP in single course of SBRT. However, it is not well known how cumulative lung dose of multiple courses of SBRT impacts incidence of RP. The purpose of the present study is to evaluate incidence of RP after multiple courses of SBRT for lung cancers.

Chest X-ray screening examinations among French uranium miners: exposure estimation and impact on radon-associated lung cancer risk

BackgroundMedical surveillance of uranium miners can include periodic chest X-ray examinations. This study aimed to assess the X-ray exposure due to occupational health monitoring in the French cohort of uranium...

Characteristics of Primary and Secondary Hepatic Malignancies Associated with Hepatopulmonary Shunting

To identify liver tumor characteristics associated with low (<10%), intermediate (10%-20%), and high (>20%) lung shunt fraction (LSF) at technetium 99m ((99m)Tc) macroaggregated albumin (MAA) imaging performed before yttrium 90 ((90)Y) radioembolization (RE). In this single-center retrospective study, 141 patients (70 with hepatocellular carcinoma [HCC], 71 with other tumors; 95 men, 45 women; median age, 61 years) underwent mapping arteriography with (99m)Tc-MAA LSF calculation before (90)Y RE from 2006 to 2012. Tumor characteristics, including tumor type, index lesion size and morphologic structure (circumscribed, infiltrative), focality (solitary oligonodular, multinodular), disease distribution (unilobar, bilobar), tumor burden (≤50%, 50%), portal vein invasion (present, absent), and arterioportal shunting (present, absent) were correlated with (99m)Tc-MAA imaging-calculated LSFs at univariate and multivariate analysis. Median LSF was 8.4% (HCC, 9.0%; other tumors, 8.3%). LSF greater than 20% occurred in 14% of HCCs, but only in 3% of other tumors (P = .004). For HCC, tumor morphologic structure (P = .022), tumor burden (P < .001), main portal vein invasion (P = .033), and arterioportal shunting (P < .001) were significantly associated with different LSF categories at univariate analysis; infiltrative morphologic structure, tumor burden greater than 50%, portal vein invasion, and shunting had confirmed association with high LSF at multivariate analysis. For other liver tumors, tumor size (P = .001) and tumor burden (P = .003) were significantly associated with different LSF categories at univariate analysis. Multivariate confirmation was precluded by small sample size. Patients underwent a median of one (90)Y RE session (range, one to six), with median per-treatment and cumulative lung doses of 6.0 Gy and 8.5 Gy, respectively. LSF greater than 20% periodically occurs in HCC but is uncommon in other liver tumors. Specific tumor characteristics are associated with LSF greater than 20% and may indicate need for interventions to reduce LSF.

Risk of Lung Cancer Mortality in Relation to Lung Doses among French Uranium Miners: Follow-Up 1956–1999

The aim of this study was to assess the risk of lung cancer death associated with cumulative lung doses from exposure to α-particle emitters, including radon gas, radon short-lived progeny, and long-lived radionuclides, and to external γ rays among French uranium miners. The French "post-55" sub-cohort included 3,377 uranium miners hired from 1956, followed up through the end of 1999, and contributing to 89,405 person-years. Lung doses were calculated with the ICRP Human Respiratory Tract Model (Publication 66) for 3,271 exposed miners. The mean "absorbed lung dose" due to α-particle radiation was 78 mGy, and that due to the contribution from other types of radiation (γ and β-particle radiation) was 56 mGy. Radon short-lived progeny accounted for 97% of the α-particle absorbed dose. Out of the 627 deaths, the cause of death was identified for 97.4%, and 66 cases were due to lung cancer. A significant excess relative risk (ERR) of lung cancer death was associated with the total absorbed lung dose (ERR/Gy = 2.94, 95% CI 0.80, 7.53) and the α-particle absorbed dose (4.48, 95% CI 1.27, 10.89). Assuming a value of 20 for the relative biological effectiveness (RBE) of α particles for lung cancer induction, the ERR/Gy-Eq for the total weighted lung dose was 0.22 (95% CI: 0.06, 0.53).

Cumulative Lung Dose for Several Motion Management Strategies as a Function of Pretreatment Patient Parameters

To evaluate patient parameters that may predict for relative differences in cumulative four-dimensional (4D) lung dose among several motion management strategies. Deformable image registration and dose accumulation were used to generate 4D treatment plans for 18 patients with 4D computed tomography scans. Three plans were generated to simulate breath hold at normal inspiration, target tracking with the beam aperture, and mid-ventilation aperture (control of the target at the mean daily position and application of an iteratively computed margin to compensate for respiration). The relative reduction in mean lung dose (MLD) between breath hold and mid-ventilation aperture (DeltaMLD(BH)) and between target tracking and mid-ventilation aperture (DeltaMLD(TT)) was calculated. Associations between these two variables and parameters of the lesion (excursion, size, location, and deformation) and dose distribution (local dose gradient near the target) were also calculated. The largest absolute and percentage differences in MLD were 1.0 Gy and 21.5% between breath hold and mid-ventilation aperture. DeltaMLD(BH) was significantly associated (p < 0.05) with tumor excursion. The DeltaMLD(TT) was significantly associated with excursion, deformation, and local dose gradient. A linear model was constructed to represent DeltaMLD vs. excursion. For each 5 mm of excursion, target tracking reduced the MLD by 4% compared with the results of a mid-ventilation aperture plan. For breath hold, the reduction was 5% per 5 mm of excursion. The relative difference in MLD among different motion management strategies varied with patient and tumor characteristics for a given dosimetric target coverage. Tumor excursion is useful to aid in stratifying patients according to appropriate motion management strategies.

Pulmonary Toxicity and Fate of Agglomerated 10 and 40 nm Aluminum Oxyhydroxides following 4-Week Inhalation Exposure of Rats: Toxic Effects are Determined by Agglomerated, not Primary Particle Size

Inhaled polydisperse micronsized agglomerated particulates composed of nanosized primary particles may exert their pulmonary toxicity in either form, depending on whether these tightly associated structures are disintegrated within the biological system or not. This hypothesis was tested in a rat bioassay using two calcined aluminum oxyhydroxides (AlOOH) consisting of primary particles in the range of 10-40 nm. Male Wistar rats were nose-only exposed to 0.4, 3, and 28 mg/m(3) in two 4-week (6 h/day, 5 days/week) inhalation studies followed by a 3-month postexposure period. The respective mass median aerodynamic diameter (MMAD) of agglomerated particles in inhalation chambers was 1.7 and 0.6 mum. At serial sacrifices, pulmonary toxicity was characterized by bronchoalveolar lavage (BAL) and histopathology. The retention kinetics of aluminum (Al) was determined in lung tissue, BAL cells, and selected extrapulmonary organs, including lung-associated lymph nodes (LALNs). Significant changes in BAL, lung, and LALN weights occurred at 28 mg/m(3). Histopathology revealed alveolar macrophages with enlarged and foamy appearance, increased epithelial cells, inflammatory cells, and focal septal thickening. The determination of aluminum in lung tissue shows that the cumulative lung dose was higher following exposure to AlOOH-40 nm/MMAD-0.6 mum than to AlOOH-10 nm/MMAD-1.7 mum, despite identical exposure concentrations. The associated pulmonary inflammatory response appears to be principally dependent on the agglomerated rather than primary particle size. Despite high lung burdens, conclusively increased extrapulmonary organ burdens did not occur at any exposure concentration and postexposure time point. Particle-induced pulmonary inflammation was restricted to cumulative doses exceeding approximately 1 mg AlOOH/g lung following 4-week exposure at 28 mg/m(3). It is concluded that the pulmonary toxicity of nanosized, agglomerated AlOOH particles appears to be determined by the size of agglomerated rather than primary particles, whereas the clearance half-time of particles appears to increase with decreased primary particle size. However, in regard to toxicokinetics, this outcome is highly contingent upon the total lung burden and especially whether overloading or non-overloading conditions were attained or not. In order to reliably demonstrate retention-related different characteristics in toxicity and fate of poorly soluble (nano)particles postexposure periods of at least 3 months appear to be indispensible.

Incidence of Radiation Pneumonitis After Hepatic Intra-Arterial Radiotherapy With Yttrium-90 Microspheres Assuming Uniform Lung Distribution

To assess the incidence of clinical and imaging radiation pneumonitis (RP) in a cohort of patients treated with >30 Gy cumulative lung dose (CLD) using Y90 microspheres. Four hundred three patients were treated with Y90 microspheres during a 4-year period. Of these, 58 patients received >30 Gy CLD. Patients were followed for toxicities suggestive of imaging or clinical RP. Toxicities were graded using the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer Late Radiation Morbidity Scoring Schema. Patients were also followed for survival from time of first treatment. There were 44 men and 14 women. Forty-three patients had hepatocellular carcinoma (HCC), whereas 15 had liver metastases. Mean and median follow-up were 7.3 and 6.0 months, respectively. Mean lung shunt fraction was slightly greater in the patients with HCC versus metastases (20% vs. 16.7%, P = 0.2308). The lifetime CLD for metastases and HCC groups were not statistically different (54.04 Gy vs. 48.44 Gy, P = 0.4303). Forty-three of 53 patients demonstrated no lung imaging findings suggestive of pneumonitis. Imaging findings in 10 patients included pleural effusions, atelectasis, and ground glass attenuation. There were no cases of clinical or imaging RP. Survival varied depending on stage as well as single and CLD. None of the patient deaths were attributed to respiratory compromise. RP was not predicted using the currently used Y90 dosimetry models that assume uniform distribution in the lungs. Further investigation and dose escalation studies are required to more precisely define the radiation tolerance of lung parenchyma using this mode of therapy.

Lung cancer risk of Mayak workers: modelling of carcinogenesis and bystander effect

Lung cancer mortality in the period of 1948-2002 has been analysed for 6,293 male workers of the Mayak Production Association, for whose information on smoking, annual external doses and annual lung doses due to plutonium exposures was available. Individual likelihoods were maximized for the two-stage clonal expansion (TSCE) model of carcinogenesis and for an empirical risk model. Possible detrimental and protective bystander effects on mutation and malignant transformation rates were taken into account in the TSCE model. Criteria for non-nested models were used to evaluate the quality of fit. Data were found to be incompatible with the model including a detrimental bystander effect. The model with a protective bystander effect did not improve the quality of fit over models without a bystander effect. The preferred TSCE model was sub-multiplicative in the risks due to smoking and internal radiation, and more than additive. Smoking contributed 57% to the lung cancer deaths, the interaction of smoking and radiation 27%, radiation 10%, and others cause 6%. An assessment of the relative biological effectiveness of plutonium was consistent with the ICRP recommended value of 20. At age 60 years, the excess relative risk (ERR) per lung dose was 0.20 (95% CI: 0.13; 0.40) Sv(-1), while the excess absolute risk (EAR) per lung dose was 3.2 (2.0; 6.2) per 10(4) PY Sv. With increasing age attained the ERR decreased and the EAR increased. In contrast to the atomic bomb survivors, a significant elevated lung cancer risk was also found for age attained younger than 55 years. For cumulative lung doses below 5 Sv, the excess risk depended linearly on dose. The excess relative risk was significantly lower in the TSCE model for ages attained younger than 55 than that in the empirical model. This reflects a model uncertainty in the results, which is not expressed by the standard statistical uncertainty bands.

Clinical evaluation of the partition model for estimating radiation doses from yttrium-90 microspheres in the treatment of hepatic cancer.

Radiation doses to the tumour and non-tumorous liver compartments from yttrium-90 microspheres in the treatment of hepatic cancer, as estimated by a partition model, have been verified by correlation with the actual doses measured with a beta probe at open surgery. The validity of the doses to the lungs, the tumour and non-tumorous liver compartment as estimated by the partition model was further evaluated in clinical settings. On the basis of the observation that one of three patients who received more than 30 Gy from a single treatment and one of two patients who received more than 50 Gy from multiple treatments developed radiation pneumonitis, it was deduced that an estimated lung dose < 30 Gy from a single treatment and a cumulative lung dose < 50 Gy from multiple treatments were probably the tolerance limits of the lungs. Three of five patients who received lung doses > 30 Gy as estimated by the partition model and were predicted to develop radiation pneumonitis, did so despite the use of partial hepatic embolization to reduce the degree of lung shunting. Furthermore, a higher radiological response rate and prolonged survival were found in the group of patients who received higher tumour doses, as estimated by the partition model, than in the group with lower estimated tumour doses. Thus the radiation doses estimated by the partition model can be used to predict (a) complication rate, (b) response rate and (c) duration of survival in the same manner as the actual radiation doses measured with a beta probe at open surgery. The partition model has made selective internal radiation therapy using 90Y microspheres safe and repeatable without laparotomy.

Uranium dust exposure and lung cancer risk in four uranium processing operations.

We examined the relation between uranium dust exposure and lung cancer mortality among workers employed in four uranium processing or fabrication operations located in Missouri, Ohio, and Tennessee. Among workers who had at least 30 years of potential follow-up, we identified 787 lung cancer cases from death certificates and matched one control to each case. Health physicists estimated individual annual lung doses from occupational exposure primarily to insoluble uranium compounds, using contemporary monitoring data. With a 10-year lag, cumulative lung doses ranged from 0 to 137 centigrays (cGy) for cases and from 0 to 80 cGy for controls. Health physicists assigned annual external radiation doses to workers having personal monitoring records. Archivists collected smoking information from occupational medical records. Odds ratios for lung cancer mortality for seven cumulative internal dose groups did not demonstrate increasing risk with increasing dose. We found an odds ratio of 2.0 for those exposed to 25 cGy and higher, but the 95% confidence interval of 0.20 to 20 showed great uncertainty in this estimate. There was a suggestion of an exposure effect for workers hired at age 45 years or older. Further analyses for cumulative external doses and exposures to thorium, radium, and radon did not reveal any clear association between exposure and increased risk, nor did dichotomizing workers by facility.

Distribution and Short-Term Effects of Intratracheally Instilled Neutron-Irradiated UO 2 Particles in the Rat

In the present study we investigated the radionuclide distribution and histopathological effects of neutron-irradiated UO 2, particles in the rat after intratracheal instillation. The kinetics and short-term effects of uranium fission products ( 95Zr, 95Nb, 103Ru and 141Ce) were examined during a 3-month follow-up period. A rapid clearance (about 21%) of particles occurred via the gastrointestinal tract within 24 hr after the instillation. Autoradiographic and histological examinations revealed that the retained particles were nonuniformly distributed in the lungs. Translocation of the fission products from the lung to various other tissues was slow; 3 months after the instillation, the activity of the total body burden was below 1% in the liver, kidney, and spleen, whereas in the lungs it was 83%. Clearance of particles appeared to be mainly due to tracheobronchial mucociliary mechanisms. Translocation of the fission products to the bone and liver was significantly less than that reported by the ICRP, indicating that the clearance of uranium-matrix-associated fission products is preferably dependent on the physical characteristics of the particulate material. The cumulative lung doses ranging from 170 to 550 mSv caused slight or moderate local inflammatory reactions in the lungs, but at smaller dose levels there were no histopathological changes observed.

Cytogenetic and Other Biological Effects of 239 PuO 2 Inhaled by the Rhesus Monkey

Sixteen immature rhesus monkeys were exposed via inhalation to an insoluble, polydisperse 239PuO2 aerosol labeled with 169Yb which had an activity median aerodynamic diameter of 1.6 gm and a (0g of 1.6. Four groups with three monkeys per group were exposed to achieve initial 239pu lung burdens of 1000-2000, 200-300, 20-65, and 2-10 nCi, respectively. To determine early retention and distribution of the aerosol, four additional monkeys were exposed with initial lung burdens of 200-600 nCi and were sacrificed 4 hr and 30 days after inhalation exposure. Two monkeys were sham exposed and served as controls. Using data derived from external whole-body counting of the 169Yb label, it was estimated that the inhaled 239PuO, was retained in the body with an average effective half-life of 1000 days with some translocation from the lung to the pulmonary lymph nodes. Chromosome aberrations were scored in blood lymphocytes cultured 1, 3, 7, 19, 31, and 43 months after inhalation. Only in animals with cumulative lung doses greater than 1000 rad was there a significant increase in the frequency of rings and dicentrics when compared to the controls. An animal with an estimated initial lung burden of 1000 nCi showed marked alterations in respiratory function 30 days prior to his death from pulmonary fibrosis 990 days after inhalation exposure. Only slight respiratory changes were detected in the other animals evaluated. To date, three monkeys have died, two with initial lung burdens of 1800 and 1000 nCi '3"Pu which died from radiation pneumonitis and the third with an initial lung burden of 20 nCi which died of gastric torsion presumably not related to Pu exposure. Comparison of survival data from rhesus monkeys with those obtained from baboons and beagles indicates that rhesus monkeys, baboons, and dogs are similar in their early response to inhaled 39"PuO2.

Biological effectiveness of 237 Np.

The intravenous injection of neptunium nitrate and oxalate at doses ranging from 2.0 to 0.017 μCi/kg was characterized by the occurrence of osteosarcomas (incidence ranging from 58 to 9 % at cumulative skeletal radiation doses ranging from 520 to 5 rads, respectively). The major manifestations of injury after intratracheal administration of the two neptunium compounds at the same doses were the development of pneumosclerosis and malignant lung tumours (incidence ranging from 37 to 11 % at cumulative lung doses of 3220-5 rads, respectively); and, to a lesser extent, of osteosarcomas (incidence ranging from 25 to 5 % at skeletal doses of 408-4 rads, respectively).