Promotion of Pulmonary Carcinogenesis by Plutonium Particle Aggregation Following Inhalation of 239 PuO 2

Sanders, C.L.; McDonald, K.E.; Lauhala, K.E.

doi:10.2307/3577383

Cited by 23 publications

(9 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The dose-response relationship appears to fit to a quadratic function and a maximum lung tumor incidence at about 8 Gy (Sanders et al, 1988;Sanders and McDonald, 1992;Sanders and Lundgren, 1995). The Sanders' observations are confirmed by two experiments in beagle dogs which had inhaled 238Pu02 and 239Pu02 (Park et al, 1991).…”

Section: Lung Cancerssupporting

confidence: 61%

Probabilistic accident consequence uncertainty analysis -- Uncertainty assessment for internal dosimetry. Volume 2: Appendices

Goossens¹,

Kraan²,

Cooke

et al. 1998

View full text Add to dashboard Cite

LEGALNOTICENeither the European Commission nor any person acting on behalf of the Commission is responsible for the use that might be made of the information in this volume. NUREGlCR-6571 ii DISCLAIMERPortions of this document may be illegible in electronic image products. Images are produced from the best available original document. AbstractThe development of two new probabilistic accident consequence codes, MACCS and COSYMA, was completed in 1990.These codes estimate the risk presented by nuclear installations based on postulated frequencies and magnitudes of potential accidents. In 1991, the US Nuclear Regulatory Commission (NRC) and the European Commission (EC) began a joint uncertainty analysis of the two codes. The ultimate objective was to develop credible and traceable uncertainty distributions for the input variables of the codes.The study was formulated jointly and was limited to the current code models and to physical quantities that could be measured in experiments. An elicitation procedure was devised from previous US and EC studies with refinements based on recent experience. Elicitation questions were developed, tested, and clarified. Internationally recognized experts were selected using a common set of criteria. Probability training exercises were conducted to establish ground rules and set the initial and boundary conditions. Experts developed their distributions independently.Aft& the first feasibility study on atmospheric dispersion and deposition parameters, a second expert judgment exercise was carried out on food chain and external dose (calculation) parameters. A third expert judgment exercise has been carried out on early and late health effects and internal dosimetry parameters. The goal again was to develop a library of uncertainty distributions for the selected consequence parameters. Nine experts from five countries were selected for an expert panel on internal dosimetry. Their results were processed with an equal-weighting aggregation method, and the aggregated distributions will be used to determine distributions on the code input parameters of the dose per unit intake (DUPI) models used in COSYMA and for MACCS. PrefaceThis volume is the second of a two-volume document that summarizes a joint project conducted by the US Nuclear Regulatory Commission and the European Commission to assess uncertainties in the MACCS and COSYMA probabilistic accident consequence codes. These codes were developed primarily for estimating the risks presented by nuclear reactors based on postulated frequencies and magnitudes of potential accidents. This document reports on an ongoing project to assess uncertainty in the MACCS and COSYMA calculations for the offsite consequences of radionuclide releases by hypothetical nuclear power plant accidents. A panel of nine experts was formed to compile credible and traceable uncertainty distributions for internal dosimetry input variables that affect calculations of offsite consequences. The expert judgment elicitation procedure and its outcomes are described in...

show abstract

Section: Lung Cancerssupporting

confidence: 61%

Probabilistic accident consequence uncertainty analysis -- Uncertainty assessment for internal dosimetry. Volume 2: Appendices

Goossens¹,

Kraan²,

Cooke

et al. 1998

View full text Add to dashboard Cite

show abstract

“…In follow-up, the purpose and objectives of this study were to 1) update the earlier, unfinished study and reassess the dose-response relationship for 239 PuO 2 -induced lung cancer in the low-dose range (0 to 50 cGy), 2) determine the risk coefficient for 239 PuO 2 -induced lung cancer, 3) test for statistical differences between controls and lowdose groups, and 4) evaluate any potential threshold for 239 PuO 2 -induced lung cancer, as was previously observed in rats at 100 cGy (Sanders et al 1998).…”

Section: Introductionmentioning

confidence: 97%

CARCINOGENESIS FROM INHALED 239PuO2 IN BEAGLES: EVIDENCE FOR RADIATION HOMEOSTASIS AT LOW DOSES?

Fisher

Weller

2010

Health Physics

View full text Add to dashboard Cite

From the early 1970's to the late 1980's, Pacific Northwest National Laboratory conducted life-span studies in beagle dogs on the biological effects of inhaled plutonium ((238)PuO(2), (239)PuO(2), and Pu[NO(3)](4)) to help predict risks associated with accidental intakes in workers. Years later, the purpose of the present follow-up study was to reassess the dose-response relationship for lung cancer in the PuO(2) dogs compared to controls-with particular focus on the dose-response at relatively low lung doses. A PuO(2) aerosol (2.3 mum activity-median aerodynamic diameter, 1.9 mum geometric standard deviation) was administered to six groups of 20 young (18-mo-old) beagle dogs (10 males and 10 females) by inhalation at six different activity levels, as previously described in Laboratory reports. Control dogs were sham-exposed. In dose level 1, initial pulmonary lung depositions were 130 + or - 48 Bq (3.5 + or - 1.3 nCi), corresponding to 1 Bq g lung tissue (0.029 + or - 0.001 nCi g(-1)). Groups 2 through 6 received initial lung depositions (mean values) of 760, 2,724, 10,345, 37,900, and 200,000 Bq (22, 79, 300, 1,100, and 5,800 nCi) PuO(2), respectively. For each dog, the absorbed dose to lungs was calculated from the initial lung burden and the final lung burden at time of death and lung mass, assuming a single, long-term retention function. Insoluble plutonium oxide exhibited long retention times in the lungs. Increased dose-dependent mortality due to lung cancer (bronchiolar-alveolar carcinoma, adenocarcinoma, and epidermoid carcinoma) and radiation pneumonitis (in the highest exposure group) were observed in dogs exposed to PuO(2). Calculated lung doses ranged from a few cGy (lowest exposure level) to 7,764 cGy in dogs that experienced early deaths from radiation pneumonitis. Data were regrouped by lifetime lung dose and plotted as a function of lung tumor incidence. The lung tumor incidence in controls and zero-dose exposed dogs was 18% (5/28). However, no lung tumors were observed in 16 dogs with the lowest lung doses (8 to 22 cGy, mean 14.4 + or - 7.6 cGy), and only one lung tumor was observed in the next 10 dogs with lung doses ranging from 27 to 48 cGy (mean 37.5 + or - 10.9 cGy). By least-squares analysis, a pure-quadratic function represented the overall dose-response (n = 137, r = 0.96) with no apparent dose-related threshold. Reducing this function to three linear dose-response components, we calculated risk coefficients for each. However, the incidence of lung tumors at zero dose was significantly greater than the incidence at low dose (at the p < or = 0.053 confidence level), suggesting a protective effect (radiation homeostasis) of alpha-particle radiation from PuO(2). If a threshold for lung cancer incidence exists, it will be observed in the range 15 to 40 cGy.

show abstract

“…The first labeling wave of nonciliated bronchiolar cells was due to the initial high dose rate delivered to the bronchiolar epithelium from deposited Pu particles that were largely cleared during the first The accumulation of labeled cells in focal alveolar and bronchiolar regions of lung due to Pu particle aggregation was clearly dose dependent, exhibiting a threshold at the same dose as lung tumor formation [5]. A similar situation is seen with formaldehyde exposure.…”

Section: Discussionmentioning

confidence: 67%

“…The low-dose portion of the curve (<Gy) may represent initiation events, while the much steeper, higher-dose portion of the curve (> 1 Gy), may represent promotion and progression events due to Pu particle aggregation [l-41. The dose-tumor response curve also indicates the presence of a "practical" threshold dose of about 1 Gy, below which large Pu particle aggregate formation is not seen [5]. An epigentic mechanism associated with a threshold dose and Pu aggregate formation is also possible; above this threshold dose there is significant cell damage and proliferative repair resulting in the clonal expansion of spontaneously occuring mutations.…”

Section: Introductionmentioning

confidence: 96%

Tritiated Thymidine-Labeled Bronchioloalveolar Cells and Radiation Dose Following Inhalation of Plutonium in Rats

Sanders¹,

Lauhala²,

McDonald³

1989

Experimental Lung Research

Self Cite

View full text Add to dashboard Cite

The goal of this study is to show the relationship of inhaled Pu particle distribution and alveolar-bronchiolar target-cell response with respect to the formation of pulmonary carcinoma. The proliferation of type 2 alveolar epithelium and nonciliated bronchiolar epithelium appears critical in the induction of lung tumors associated from inhaled 239PuO2. Female, Wistar rats were either sham-exposed (40 rats) or given a single inhalation to 169Yb-239PuO2 (99 rats, ILB, 3.9 +/- 1.2 kBq) and examined at 20 time intervals from 1 day to 700 days postexposure for Pu particle distribution in airways by SEM quantitative autoradiography and for cell labeling with tritiated thymidine. Initially, deposited Pu particles were rapidly cleared from the surface of the trachea, bronchi, and bronchioles within a few days. Thereafter, about 5 times more alpha track exposure to the bronchiolar epithelium was delivered from Pu particles found in peribronchiolar alveoli than from Pu particles being cleared from bronchiolar surfaces. Exposure of bronchiolar epithelium at later times was due mostly to the formation of peribronchiolar Pu particle aggregates. A maximal increase in labeled alveolar wall cells was seen at 60 days after exposure, decreasing gradually to control levels by 400 days. Cell labeling in focal alveolar regions of Pu aggregation was about 5 fold higher. Increased bronchiolar epithelium labeling appeared in two phases. The first phase was seen 15 days after exposure, associated with initial deposition and clearance of Pu particles. The second phase slowly reached a maximum at 250 days and was associated with peribronchiolar Pu aggregate formation. The temporal-spatial dose-distribution pattern for inhaled Pu particles is an important aspect of Pu-induced pulmonary carcinogenesis.

show abstract

Promotion of Pulmonary Carcinogenesis by Plutonium Particle Aggregation Following Inhalation of 239 PuO 2

Cited by 23 publications

References 0 publications

Probabilistic accident consequence uncertainty analysis -- Uncertainty assessment for internal dosimetry. Volume 2: Appendices

Probabilistic accident consequence uncertainty analysis -- Uncertainty assessment for internal dosimetry. Volume 2: Appendices

CARCINOGENESIS FROM INHALED 239PuO2 IN BEAGLES: EVIDENCE FOR RADIATION HOMEOSTASIS AT LOW DOSES?

Tritiated Thymidine-Labeled Bronchioloalveolar Cells and Radiation Dose Following Inhalation of Plutonium in Rats

Contact Info

Product

Resources

About