Biological Effects of Inhaled 239PuO2 in Beagles
Seven groups of 8–24 Beagle dogs, exposed to 239PuO2 aerosols by inhalation [mean initial lung depositions (ILD) of 0.0, 0.14, 0.63, 3.2, 13, 44 and 210 kBq] were observed throughout their lives to determine tissues at risk and dose-effect relationships. The mean average pulmonary retention half-tim...
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| Veröffentlicht in: | Radiation research 2012-11, Vol.178 (5), p.447-467 |
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| creator | Park, James F. Watson, Charles R. Buschbom, Ray L. Dagle, Gerald E. Strom, Daniel J. Weller, Richard E. |
| description | Seven groups of 8–24 Beagle dogs, exposed to 239PuO2 aerosols by inhalation [mean initial lung depositions (ILD) of 0.0, 0.14, 0.63, 3.2, 13, 44 and 210 kBq] were observed throughout their lives to determine tissues at risk and dose-effect relationships. The mean average pulmonary retention half-time of 239Pu was 1,192 days. Most (70%) of the plutonium recovered at death in dogs surviving >10 years after exposure was found in the thoracic lymph nodes with ∼15% in lung, ∼10% in liver and ∼2% in bone. Eight dogs at the highest exposure levels died from radiation pneumonitis prior to a minimal 3-year latency period after exposure for the observation of lung tumors, with the first succumbing 337 days after exposure. Of 108 plutonium-exposed Beagles with ILD |
| doi_str_mv | 10.1667/RR2504.1 |
| format | Article |
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The mean average pulmonary retention half-time of 239Pu was 1,192 days. Most (70%) of the plutonium recovered at death in dogs surviving >10 years after exposure was found in the thoracic lymph nodes with ∼15% in lung, ∼10% in liver and ∼2% in bone. Eight dogs at the highest exposure levels died from radiation pneumonitis prior to a minimal 3-year latency period after exposure for the observation of lung tumors, with the first succumbing 337 days after exposure. Of 108 plutonium-exposed Beagles with ILD <100 kBq, 51 (47%) had lung tumors with significantly increased incidence in those dogs with total lung dose of ≥1.1 Gy at death. The primary non-neoplastic effects observed were lymphopenia, atrophy and fibrosis of the thoracic lymph nodes, radiation pneumonitis and pulmonary fibrosis, and bacterial pneumonia. Lesions of the thoracic lymph nodes were observed in 98 of 108 exposed dogs, but there were no primary neoplasms of the lymph nodes. Bacterial pneumonia was observed in 13 plutonium-exposed dogs and was the most notable non-neoplastic cause of death, with survival nearly the same as that of controls. Setting of dose limits on the basis of detrimental effects commonly considers and differentiates between stochastic and deterministic effects, raising the question of whether the non-neoplastic effects found in this study were deterministic. The International Commission on Radiation Protection (ICRP), National Council on Radiation Protection & Measurements (NCRP), and similar organizations generally consider effects that increase in incidence and severity to meet the definition of deterministic. We demonstrated the radiation dose-related nature of effects such as pneumonitis and fibrosis graphically and lymphopenia numerically, rather than by quantified estimates. It is clear, however, that both incidence and severity increased with ILD and radiation dose and should be considered as deterministic effects.</description><identifier>ISSN: 0033-7587</identifier><identifier>EISSN: 1938-5404</identifier><identifier>DOI: 10.1667/RR2504.1</identifier><identifier>PMID: 22998225</identifier><language>eng</language><publisher>United States: The Radiation Research Society</publisher><subject>Administration, Inhalation ; Animals ; Bone and Bones - pathology ; Bone and Bones - radiation effects ; Causes of death ; Dogs ; Dose-Response Relationship, Radiation ; Dosimetry ; Inhalation ; Liver ; Liver - pathology ; Liver - radiation effects ; Lung - pathology ; Lung - radiation effects ; Lungs ; Lymph nodes ; Lymph Nodes - pathology ; Lymph Nodes - radiation effects ; Plutonium ; Plutonium - toxicity ; Radiation ; Radiation pneumonitis ; Radiation Pneumonitis - pathology ; REGULAR ARTICLES ; Space life sciences ; Survival Analysis ; Tissue Distribution ; Tumors</subject><ispartof>Radiation research, 2012-11, Vol.178 (5), p.447-467</ispartof><rights>Copyright © 2012 Radiation Research Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/41679893$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/41679893$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,780,784,803,27915,27916,58008,58241</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22998225$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Park, James F.</creatorcontrib><creatorcontrib>Watson, Charles R.</creatorcontrib><creatorcontrib>Buschbom, Ray L.</creatorcontrib><creatorcontrib>Dagle, Gerald E.</creatorcontrib><creatorcontrib>Strom, Daniel J.</creatorcontrib><creatorcontrib>Weller, Richard E.</creatorcontrib><title>Biological Effects of Inhaled 239PuO2 in Beagles</title><title>Radiation research</title><addtitle>Radiat Res</addtitle><description>Seven groups of 8–24 Beagle dogs, exposed to 239PuO2 aerosols by inhalation [mean initial lung depositions (ILD) of 0.0, 0.14, 0.63, 3.2, 13, 44 and 210 kBq] were observed throughout their lives to determine tissues at risk and dose-effect relationships. The mean average pulmonary retention half-time of 239Pu was 1,192 days. Most (70%) of the plutonium recovered at death in dogs surviving >10 years after exposure was found in the thoracic lymph nodes with ∼15% in lung, ∼10% in liver and ∼2% in bone. Eight dogs at the highest exposure levels died from radiation pneumonitis prior to a minimal 3-year latency period after exposure for the observation of lung tumors, with the first succumbing 337 days after exposure. Of 108 plutonium-exposed Beagles with ILD <100 kBq, 51 (47%) had lung tumors with significantly increased incidence in those dogs with total lung dose of ≥1.1 Gy at death. The primary non-neoplastic effects observed were lymphopenia, atrophy and fibrosis of the thoracic lymph nodes, radiation pneumonitis and pulmonary fibrosis, and bacterial pneumonia. Lesions of the thoracic lymph nodes were observed in 98 of 108 exposed dogs, but there were no primary neoplasms of the lymph nodes. Bacterial pneumonia was observed in 13 plutonium-exposed dogs and was the most notable non-neoplastic cause of death, with survival nearly the same as that of controls. Setting of dose limits on the basis of detrimental effects commonly considers and differentiates between stochastic and deterministic effects, raising the question of whether the non-neoplastic effects found in this study were deterministic. The International Commission on Radiation Protection (ICRP), National Council on Radiation Protection & Measurements (NCRP), and similar organizations generally consider effects that increase in incidence and severity to meet the definition of deterministic. We demonstrated the radiation dose-related nature of effects such as pneumonitis and fibrosis graphically and lymphopenia numerically, rather than by quantified estimates. It is clear, however, that both incidence and severity increased with ILD and radiation dose and should be considered as deterministic effects.</description><subject>Administration, Inhalation</subject><subject>Animals</subject><subject>Bone and Bones - pathology</subject><subject>Bone and Bones - radiation effects</subject><subject>Causes of death</subject><subject>Dogs</subject><subject>Dose-Response Relationship, Radiation</subject><subject>Dosimetry</subject><subject>Inhalation</subject><subject>Liver</subject><subject>Liver - pathology</subject><subject>Liver - radiation effects</subject><subject>Lung - pathology</subject><subject>Lung - radiation effects</subject><subject>Lungs</subject><subject>Lymph nodes</subject><subject>Lymph Nodes - pathology</subject><subject>Lymph Nodes - radiation effects</subject><subject>Plutonium</subject><subject>Plutonium - toxicity</subject><subject>Radiation</subject><subject>Radiation pneumonitis</subject><subject>Radiation Pneumonitis - pathology</subject><subject>REGULAR ARTICLES</subject><subject>Space life sciences</subject><subject>Survival Analysis</subject><subject>Tissue Distribution</subject><subject>Tumors</subject><issn>0033-7587</issn><issn>1938-5404</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kE9PwkAQxTdGI4gmfgFNT8ZLcWb_do9CUElIMETPzbbdxZLSxS49-O0pKXKaTN5vJu89Qu4RxiilelmtqAA-xgsyRM2SWHDgl2QIwFisRKIG5CaEDXQ7Sn1NBpRqnVAqhgQmpa_8usxNFc2cs_k-RN5F8_rHVLaIKNOf7ZJGZR1NrFlXNtySK2eqYO9Oc0S-32Zf0494sXyfT18XcYagRewynhRSceckRa1d5y-nFLgFwx0vQGYsEfToU9m8MJlCcFIKQFt0p06wEXnu_-4a_9vasE-3ZchtVZna-jakiAKBKdZlGpHHE9pmW1uku6bcmuYv_U_ZAQ89sAl735x1jlLpRLNOf-r1rPS-tmcAIT3Wm_b1psgOKBBkvQ</recordid><startdate>201211</startdate><enddate>201211</enddate><creator>Park, James F.</creator><creator>Watson, Charles R.</creator><creator>Buschbom, Ray L.</creator><creator>Dagle, Gerald E.</creator><creator>Strom, Daniel J.</creator><creator>Weller, Richard E.</creator><general>The Radiation Research Society</general><general>Radiation Research Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>201211</creationdate><title>Biological Effects of Inhaled 239PuO2 in Beagles</title><author>Park, James F. ; Watson, Charles R. ; Buschbom, Ray L. ; Dagle, Gerald E. ; Strom, Daniel J. ; Weller, Richard E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b1095-fb48d674ff62199f250c2204e0a4f4d06b385254047ecdab710f66501edfb4f53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Administration, Inhalation</topic><topic>Animals</topic><topic>Bone and Bones - pathology</topic><topic>Bone and Bones - radiation effects</topic><topic>Causes of death</topic><topic>Dogs</topic><topic>Dose-Response Relationship, Radiation</topic><topic>Dosimetry</topic><topic>Inhalation</topic><topic>Liver</topic><topic>Liver - pathology</topic><topic>Liver - radiation effects</topic><topic>Lung - pathology</topic><topic>Lung - radiation effects</topic><topic>Lungs</topic><topic>Lymph nodes</topic><topic>Lymph Nodes - pathology</topic><topic>Lymph Nodes - radiation effects</topic><topic>Plutonium</topic><topic>Plutonium - toxicity</topic><topic>Radiation</topic><topic>Radiation pneumonitis</topic><topic>Radiation Pneumonitis - pathology</topic><topic>REGULAR ARTICLES</topic><topic>Space life sciences</topic><topic>Survival Analysis</topic><topic>Tissue Distribution</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Park, James F.</creatorcontrib><creatorcontrib>Watson, Charles R.</creatorcontrib><creatorcontrib>Buschbom, Ray L.</creatorcontrib><creatorcontrib>Dagle, Gerald E.</creatorcontrib><creatorcontrib>Strom, Daniel J.</creatorcontrib><creatorcontrib>Weller, Richard E.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Radiation research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Park, James F.</au><au>Watson, Charles R.</au><au>Buschbom, Ray L.</au><au>Dagle, Gerald E.</au><au>Strom, Daniel J.</au><au>Weller, Richard E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Biological Effects of Inhaled 239PuO2 in Beagles</atitle><jtitle>Radiation research</jtitle><addtitle>Radiat Res</addtitle><date>2012-11</date><risdate>2012</risdate><volume>178</volume><issue>5</issue><spage>447</spage><epage>467</epage><pages>447-467</pages><issn>0033-7587</issn><eissn>1938-5404</eissn><abstract>Seven groups of 8–24 Beagle dogs, exposed to 239PuO2 aerosols by inhalation [mean initial lung depositions (ILD) of 0.0, 0.14, 0.63, 3.2, 13, 44 and 210 kBq] were observed throughout their lives to determine tissues at risk and dose-effect relationships. The mean average pulmonary retention half-time of 239Pu was 1,192 days. Most (70%) of the plutonium recovered at death in dogs surviving >10 years after exposure was found in the thoracic lymph nodes with ∼15% in lung, ∼10% in liver and ∼2% in bone. Eight dogs at the highest exposure levels died from radiation pneumonitis prior to a minimal 3-year latency period after exposure for the observation of lung tumors, with the first succumbing 337 days after exposure. Of 108 plutonium-exposed Beagles with ILD <100 kBq, 51 (47%) had lung tumors with significantly increased incidence in those dogs with total lung dose of ≥1.1 Gy at death. The primary non-neoplastic effects observed were lymphopenia, atrophy and fibrosis of the thoracic lymph nodes, radiation pneumonitis and pulmonary fibrosis, and bacterial pneumonia. Lesions of the thoracic lymph nodes were observed in 98 of 108 exposed dogs, but there were no primary neoplasms of the lymph nodes. Bacterial pneumonia was observed in 13 plutonium-exposed dogs and was the most notable non-neoplastic cause of death, with survival nearly the same as that of controls. Setting of dose limits on the basis of detrimental effects commonly considers and differentiates between stochastic and deterministic effects, raising the question of whether the non-neoplastic effects found in this study were deterministic. The International Commission on Radiation Protection (ICRP), National Council on Radiation Protection & Measurements (NCRP), and similar organizations generally consider effects that increase in incidence and severity to meet the definition of deterministic. We demonstrated the radiation dose-related nature of effects such as pneumonitis and fibrosis graphically and lymphopenia numerically, rather than by quantified estimates. It is clear, however, that both incidence and severity increased with ILD and radiation dose and should be considered as deterministic effects.</abstract><cop>United States</cop><pub>The Radiation Research Society</pub><pmid>22998225</pmid><doi>10.1667/RR2504.1</doi><tpages>21</tpages></addata></record> |
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| subjects | Administration, Inhalation Animals Bone and Bones - pathology Bone and Bones - radiation effects Causes of death Dogs Dose-Response Relationship, Radiation Dosimetry Inhalation Liver Liver - pathology Liver - radiation effects Lung - pathology Lung - radiation effects Lungs Lymph nodes Lymph Nodes - pathology Lymph Nodes - radiation effects Plutonium Plutonium - toxicity Radiation Radiation pneumonitis Radiation Pneumonitis - pathology REGULAR ARTICLES Space life sciences Survival Analysis Tissue Distribution Tumors |
| title | Biological Effects of Inhaled 239PuO2 in Beagles |
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