Statistical Modeling of Carcinogenic Risks in Dogs That Inhaled 238 PuO 2

Abstract

Combined analyses of data on 260 life-span beagle dogs that inhaled 238PuO2 at the Inhalation Toxicology Research Institute (ITRI) and at Pacific Northwest National Laboratory (PNNL) were conducted. The hazard functions (age-specific risks) for incidence of lung, bone and liver tumors were modeled as a function of cumulative radiation dose, and estimates of lifetime risks based on the combined data were developed. For lung tumors, linear-quadratic functions provided an adequate fit to the data from both laboratories, and linear functions provided an adequate fit when analyses were restricted to doses less than 20 Gy. The estimated risk coefficients for these functions were significantly larger when based on ITRI data compared to PNNL data, and dosimetry biases are a possible explanation for this difference. There was also evidence that the bone tumor response functions differed for the two laboratories, although these differences occurred primarily at high doses. These functions were clearly nonlinear (even when restricted to average skeletal doses less than 1 Gy), and evidence of radiation-induced bone tumors was found for doses less than 0.5 Gy in both laboratories. Liver tumor risks were similar for the two laboratories, and linear functions provided an adequate fit to these data. Lifetime risk estimates for lung and bone tumors derived from these data had wide confidence intervals, but were consistent with estimates currently used in radiation protection. The dog-based lifetime liver tumor risk estimate was an order of magnitude larger than that used in radiation protection, but the latter also carries large uncertainties. The application of common statistical methodology to data from two studies has allowed the identification of differences in these studies and has provided a basis for common risk estimates based on both data sets.

Risks of Fatal Cancer From Inhalation of 239,240plutonium by Humans

“…The 5 th and 95 th percentiles of the distribution are 0.038 Gy Ϫ1 and 0.46 Gy Ϫ1 , respectively. The risk of liver cancer derived from the combined analysis of studies of 238 Pu inhalation by Beagle dogs (Gilbert et al 1998) appear to be about 10 times higher than those in humans exposed to Thorotrast. Estimates of liver cancer risks in animals were derived from beagle dog studies at Hanford and ITRI, where exposure was by inhalation Gilbert et al 1998), and at the University of Utah where exposure was by injection .…”

“…Lung cancer risk estimates from animal studies are highly variable. A combined analysis of dogs exposed to 238 Pu (Gilbert et al 1998) that included the same dogs analyzed by Muggenburg et al (1996) yielded a lung cancer risk estimate from plutonium exposure of 2,150 cases per 10 4 dog-Gy, with a broad 95% confidence interval of 210 -5,000 cases per 10 4 dog-Gy. Risk estimates for rats exposed to 239 PuO 2 also fall within this range (Sanders et al 1988(Sanders et al , 1993Sanders and Lundgren 1995).…”

“…Estimates of liver cancer risks in animals were derived from beagle dog studies at Hanford and ITRI, where exposure was by inhalation Gilbert et al 1998), and at the University of Utah where exposure was by injection . Because of the broad range of reported values, a log-triangular distribution was used to represent the incidence risk coefficient distribution that ranged from 0.02 Gy Ϫ1 to 0.80 Gy Ϫ1 , with a mode of 0.20 Gy Ϫ1 .…”

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

“…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).…”

Uncertainties Analysis for the Plutonium Dosimetry Model, Doses-2005, Using Mayak Bioassay Data

“…Table 3 contains a summary of the masses, with their respective uncertainties, used in the Doses-2005 algorithm and subsequent analysis. Whereas the biokinetic data for the model parameters are often obtained from dog studies such as research performed using beagles (Hickman et al 1995;Polig 1997;Gilbert et al 1998;Polig et al 2000), significant efforts have been executed to confirm the reliability of such data for human studies (Leggett 2001(Leggett , 2003Harrison et al 2001). …”