Biological Effects of Inhaled 238 PuO 2 in Beagles

Abstract

Beagle dogs exposed to 238PuO2 aerosols (136 dogs, 13-22 per group, mean initial lung depositions of 0.0, 0.13, 0.68, 3.1, 13, 52 and 210 kBq) were observed throughout life to determine tissues at risk and dose-effect relationships. The pulmonary retention of 238Pu was represented by the sum of two exponentially decreasing components of the initial lung deposition; about 84% cleared with a 174-day half-time; the half-time of the remainder was 908 days. The average percentages of final body burden found in lung, skeleton, liver and thoracic lymph nodes in the 30 longest-surviving dogs (mean survival 14 years) were 1, 46, 42 and 6%, respectively. Of 116 beagles exposed to plutonium, 34 (29%) developed bone tumors, 31 (27%) developed lung tumors, and 8 (7%) developed liver tumors. Although lungs accumulated a higher average radiation dose than skeleton, more deaths were due to bone tumors than to lung tumors. Deterministic effects included radiation pneumonitis, osteodystrophy, hepatic nodular hyperplasia, lymphopenia, neutropenia and sclerosing tracheobronchial lymphadenitis. Hypoadrenocorticism was also observed in a few dogs. Increased serum alanine aminotransferase, indicative of liver damage, was observed in groups with > or =3.1 kBq initial lung deposition. Estimates of cumulative tissue dose in a human exposed to airborne 238PuO2 for 50 years at a rate of one annual limit on intake each year were derived based on a comparison of the data on metabolism for humans and beagles. The 50-year dose estimates for humans are an order of magnitude lower than doses at which increased incidence of neoplasia was observed in these dogs, whereas the projected doses to humans from 50-year exposure at the annual limit of intake are of similar magnitude to those at which deterministic effects were seen in the beagles.

Macrophages as key elements of Mixed-oxide [U-Pu(O2)] distribution and pulmonary damage after inhalation?

“…Pathological consequences of actinide exposure include both stochastic eff ects, mainly tumors of epithelial origin and determinist eff ects, such as radiation pneumonitis and interstitial fi brosis (Talbot and Moores 1985, Sanders et al 1988, Diel et al 1992, Dudoignon et al 2003, Newman et al 2005, Muggenburg et al 2008, Griffi ths et al 2010, Park et al 2012). Th ese have been described both in experimental animals and in nuclear workers, such as the cohort from Mayak (Bair et al 1989, Sanders et al 1993, Gilbert et al 2004, Sokolnikov et al 2008.…”

Lung, Liver and Bone Cancer Mortality After Plutonium Exposure in Beagle Dogs and Nuclear Workers

“…Data on dogs sacrificed at specified intervals allowed us to directly estimate our lung-retention function for 238 PuO 2 . Liver-and bone-retention functions for 238 PuO 2 are those given by Park and colleagues in an analysis of PNNL dogs (Park et al 1997). Lung-and liver-retention functions for 239 Pu(NO 3 ) 4 are those used by Dagle and colleagues in an analysis of PNNL dogs, while the bone-retention function was estimated directly from data on sacrificed dogs (Dagle et al 1989(Dagle et al , 1996.…”

“…Full descriptions of these studies have been published (Gilbert et al 1998;Muggenburg et al 1996Muggenburg et al , 2008Park et al 1997). In short, the dogs were exposed once to a sufficient amount of either 239 PuO 2 , 238 PuO 2 , or 239 Pu(NO 3 ) 4 to reach a specified initial level of activity in the lung, the initial lung burden (ILB).…”

Annex D. Radiation Effects in Reference Animals and Plants

“…(D6) With respect to internal deposition of radionuclides, exposure of male and female dogs to a single inhalation of 238 Pu, at doses of 1.64 Gy or higher (cumulative dose in lung to death; Internal Lung Burden = 1.05 kBq/kg body weight), led to a reduction in life span to 80% of the control value (Weller et al, 1995;Muggenburg et al, 1996;Park et al, 1997).…”