title: Toxicity of inhaled plutonium dioxide in beagle dogs.
abstract: This study was conducted to determine the biological effects of inhaled 238PuO2 over the life spans of 144 beagle dogs. The dogs inhaled one of two sizes of monodisperse aerosols of 238PuO2 to achieve graded levels of initial lung burden (ILB). The aerosols also contained 169Yb to provide a gamma-ray-emitting label for the 238Pu inhaled by each dog. Excreta were collected periodically over each dog's life span to estimate plutonium excretion; at death, the tissues were analyzed radiochemically for plutonium activity. The tissue content and the amount of plutonium excreted were used to estimate the ILB. These data for each dog were used in a dosimetry model to estimate tissue doses. The lung, skeleton and liver received the highest alpha-particle doses, ranging from 0.16-68 Gy for the lung, 0.08-8.7 Gy for the skeleton and 0.18-19 for the liver. At death all dogs were necropsied, and all organs and lesions were sampled and examined by histopathology. Findings of non-neoplastic changes included neutropenia and lymphopenia that developed in a dose-related fashion soon after inhalation exposure. These effects persisted for up to 5 years in some animals, but no other health effects could be related to the blood changes observed. Radiation pneumonitis was observed among the dogs with the highest ILBs. Deaths from radiation pneumonitis occurred from 1.5 to 5.4 years after exposure. Tumors of the lung, skeleton and liver occurred beginning at about 3 years after exposure. Bone tumors found in 93 dogs were the most common cause of death. Lung tumors found in 46 dogs were the second most common cause of death. Liver tumors, which were found in 20 dogs but were the cause of death in only two dogs, occurred later than the tumors in bone and lung. Tumors in these three organs often occurred in the same animal and were competing causes of death. These findings in dogs suggest that similar dose-related biological effects could be expected in humans accidentally exposed to 238PuO2.
authors.affiliation: Inhalation Toxicology Research Institute, Alburquerque, New Mexico 87185, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Muggenburg
authors.forename: R A
authors.initials: RA
authors.lastname: Guilmette
authors.forename: J A
authors.initials: JA
authors.lastname: Mewhinney
authors.forename: N A
authors.initials: NA
authors.lastname: Gillett
authors.forename: J L
authors.initials: JL
authors.lastname: Mauderly
authors.forename: W C
authors.initials: WC
authors.lastname: Griffith
authors.forename: J H
authors.initials: JH
authors.lastname: Diel
authors.forename: B R
authors.initials: BR
authors.lastname: Scott
authors.forename: F F
authors.initials: FF
authors.lastname: Hahn
authors.forename: B B
authors.initials: BB
authors.lastname: Boecker
mesh_terms: D000280:Administration, Inhalation; D000512:Alpha Particles; D000818:Animals; D001822:Body Burden; D001859:Bone Neoplasms / Q000209:etiology / Q000473:pathology*; D004285:Dogs; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005720:Gamma Rays; D008136:Longevity / Q000528:radiation effects*; D008175:Lung Neoplasms / Q000145:classification / Q000209:etiology / Q000473:pathology*; D008297:Male; D009381:Neoplasms, Radiation-Induced / Q000473:pathology*; D012516:Osteosarcoma / Q000209:etiology / Q000473:pathology*; D011005:Plutonium / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D016016:Proportional Hazards Models; D011833:Radiation Injuries, Experimental; D012016:Reference Values; D012044:Regression Analysis; D012119:Respiration / Q000528:radiation effects; D012727:Sex Characteristics; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: C026885:plutonium dioxide; D011005:Plutonium