LUNG FIBROSIS AND LUNG CANCER INCIDENCE IN BEAGLE DOGS THAT INHALED (PuO2)-Pu-238 OR (PuO2)-Pu-239 (Reprinted from Health Physics, vol 96, pg 175-185, 2009)

Determination of radiation protection guidelines for persons working with plutonium has been complicated by limited human data on the biological behavior and subsequent health effects from internally deposited plutonium. One solution has been the use of animal models to predict likely health effects in humans. To compare the relationships between plutonium inhalation and lung fibrosis and lung cancer, data from life-span studies of beagle dogs given a single exposure to either plutonium-238 dioxide ((PuO2)-Pu-238) or plutonium-239 dioxide ((PuO2)-Pu-239) were analyzed. Estimates of the cumulative hazard of lung fibrosis and lung cancer after exposure to either were generated. The hazard of lung fibrosis was not consistent with a linear no-threshold model, although the magnitude of the threshold differed by radionuclide. In dogs given (PuO2)-Pu-239, the best model of lung fibrosis incorporated a linear dose-response function; a linear-quadratic dose-response function fit the data better in dogs given (PuO2)-Pu-238. At any given cumulative dose, the lung fibrosis hazard was greater for dogs given (PuO2)-Pu-238. In dogs given (PuO2)-Pu-238, with or without covariates, a quadratic dose-response function for lung cancer hazard fit better than a linear no-threshold model. In dogs given (PuO2)-Pu-239, models of lung cancer with the dose-response function as the sole predictor variable were consistent with a linear no-threshold model; however, a quadratic dose-response function with a cell-killing term fit better. These findings have implications for radiation protection because, while lung cancer hazard was dependent on cumulative dose, regardless of isotope, the lung fibrosis hazard depended on both cumulative dose and isotope. Health Phys. 96(4):493-503; 2009