Biological Effects of Inhaled²³⁹PuO₂in Beagles

Abstract

Seven groups of 8-24 Beagle dogs, exposed to (239)PuO(2) 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 (239)Pu 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.

How the Science of Radiation Biology Can Help Reduce the Crippling Fear of Low-level Radiation

“…The cancer hazard associated with 239 Pu is dependent on the radiation dose, dose rate and dose distribution (Jee 1976; Brooks et al 1983; Park et al 2012; McClellan 2014). This research has demonstrated that 239 Pu is not unique and that the biological response to the alpha particle from 239 Pu is the same as any other alpha emitter.…”

“…Such data was combined with other information by standard setting groups resulting in a radiation weighting factor of 20 being used when comparing the risks from alpha emitters to that from beta-gamma exposures (NCRP 1990; US NRC 1992). However, extensive studies in beagle dogs demonstrated that the important risk (i.e., for radiation-induced cancer) from 239 Pu is only about a factor of 6 to 10 times as effective as radiation exposure to low LET radiation (Muggenberg et al 2008; Park et al 2012; McClellan 2014). These data have been compared to human data following exposure at the Mayak facility in Russia (Gilbert et al 2007, 2013a and b) that occurred during development of atomic weapons.…”

Radiobiology of Select Radionuclides in Hanford Site Tank Waste

“…Such data combined with other information resulted in a radiation weighting factor of 20 being used when comparing the risks from alpha emitters to that from beta-gamma exposures (NCRP 1993). However, extensive studies in beagle dogs demonstrate that the cancer risk from 239/240 Pu is only about a factor of 6 to 10 times as effective as acute radiation exposure to low-LET radiation (Park et al 2012; Muggenberg et al 2008; McClellan 2014). These data have been compared to human data following exposure at the Mayak facility in Russia that occurred during development of atomic weapons.…”

“…This factor was in part driven by the observation that the frequency of chromosome aberrations induced in the liver were 20 times higher for alpha particles relative to chronic exposure to low-LET radiation. Recent research has suggested that for the induction of cancer from plutonium, the effectiveness factor relative to low LET protracted exposure is between 6 and 10 (NCRP 2001; McClellan 2014; Muggenberg et al 2008; Park et al 2012). This would reduce the risk by about a factor of 2.…”

A Nontarget Mechanism to Explain Carcinogenesis Following α-Irradiation

“…Finally, α-irradiation, leading to cancer in the presence of tissue fibrosis, is indicated in humans and animals for the irradiated lung (pulmonary fibrosis) following the inhalation of α-emitters, 31- 34 liver (cirrhosis) following thorium-232 ( 232 Th) colloid administration 35,36 and in the skeleton (peritrabecular fibrosis/osteonecrosis) following intakes of bone-seeking radionuclides—including americium-241 ( 241 Am) 37 and radium-226 ( 226 Ra; first described for 226 Ra in man by Lloyd and Henning 38 ). In dogs injected with 239 Pu, the percentage of animals with both osteosarcoma and peritrabecular fibrosis was the same over a wide range of administered doses and the prevalence of adenocarcinomas and squamous lung tumors closely matched pulmonary fibrosis.…”