STATISTICAL MODELING OF CARCINOGENIC RISKS IN DOGS THAT INHALED (PUO2)-PU-238

Combined analyses of data on 260 life-span beagle dogs that inhaled (P uO2)-Pu-238 at the Inhalation Toxicology Research Institute (ITRI) and at Pacific Northwest National Laboratory (PNNL) were conducted. The h azard functions (age-specific risks) for incidence of lung, bone and l iver tumors were modeled as a function of cumulative radiation dose, a nd estimates of lifetime risks based on the combined data were develop ed. For lung tumors, linear-quadratic functions provided an adequate f it to the data from both laboratories, and linear functions provided a n adequate fit when analyses were restricted to doses less than 20 Gy. The estimated risk coefficients for these functions were significantl y 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 l aboratories, although these differences occurred primarily at high dos es. These functions were clearly nonlinear (even when restricted to av erage skeletal doses less than 1 Gy), and evidence of radiation-induce d bone tumors was found for doses less than 0.5 Gy in both laboratorie s. Liver tumor risks were similar for the two laboratories, and linear functions provided an adequate fit to these data. Lifetime risk estim ates for lung and bone tumors derived from these data had wide confide nce intervals, but were consistent with estimates currently used in ra diation protection. The dog-based lifetime liver tumor risk estimate w as 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 th e identification of differences in these studies and has provided a ba sis for common risk estimates based on both data sets. (C) 1998 by Rad iation Research Society.