title: Distribution and biological effects of inhaled 239Pu(NO3)4 in cynomolgus monkeys.
abstract: Twenty male cynomolgus monkeys were exposed by inhalation either to an aerosol of 239Pu(NO3)4 to produce projected initial lung burdens of either 40, 10, or 4 kBq or to a carrier aerosol as a control. Animals died or were sacrificed at 0.01, 1, 3, 6, 12, 24, 40, and 99 months after inhalation, and the distribution and biological effects of the 239Pu were determined. The 239Pu cleared efficiently from the lungs so that less than 0.05 kBq remained at 99 months after exposure to 40 kBq. Total skeletal 239Pu activity was nearly constant after the first year, but the fraction of the body burden in skeleton at sacrifice increased with time up to 99 months because of clearance from other organs. Plutonium in the liver increased to a peak at 1 year and then decreased to about 10% of the peak value at 99 months. Plutonium in the testes was localized in the interstitial tissue with only 0.01 to 0.002% of the projected lung burden remaining in testes at 99 months after inhalation. Three animals exposed to 40 kBq of 239Pu died of radiation-related pulmonary pneumonitis and fibrosis. A primary papillary adenocarcinoma of the lung was identified in one animal exposed to 40 kBq initial lung burden and sacrificed 99 months after inhalation. The frequency of chromosome aberrations in blood lymphocytes was significantly elevated only in monkeys with projected deposits of 40 kBq of 239Pu. There was no change in aberration frequency in other exposure groups as a function of inhaled activity, time after exposure, or calculated total dose to the lungs. Only in monkeys that had marked radiation-induced pathological changes in the lung did the frequency of chromosome-type aberrations increase significantly, to a value about twice the control level. In cynomolgus monkeys, chromosome aberration frequency in blood lymphocytes is not a good indicator of radiation dose or damage from inhaled soluble plutonium.
authors.affiliation: Lovelace Inhalation Toxicology Research Institute, Albuquerque, New Mexico 87185.
authors.forename: A L
authors.initials: AL
authors.lastname: Brooks
authors.forename: R A
authors.initials: RA
authors.lastname: Guilmette
authors.forename: F F
authors.initials: FF
authors.lastname: Hahn
authors.forename: P J
authors.initials: PJ
authors.lastname: Haley
authors.forename: B A
authors.initials: BA
authors.lastname: Muggenburg
authors.forename: J A
authors.initials: JA
authors.lastname: Mewhinney
authors.forename: R O
authors.initials: RO
authors.lastname: McClellan
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D002869:Chromosome Aberrations; D008168:Lung / Q000528:radiation effects; D008214:Lymphocytes / Q000528:radiation effects; D008252:Macaca fascicularis; D008297:Male; D009566:Nitrates; D011005:Plutonium / Q000008:administration & dosage / Q000493:pharmacokinetics; D011830:Radiation Effects; D014018:Tissue Distribution
chemical_list: D009566:Nitrates; C015459:plutonium nitrate; D011005:Plutonium