DOSE RESPONSES FROM INHALED MONODISPERSE AEROSOLS OF (CM2O3)-CM-244 IN THE LUNG, LIVER AND SKELETON OF F344 RATS AND COMPARISON WITH (PUO2)-PU-239

The purpose of this study was to obtain information on the alpha-parti cle dose-response relationship of Cm-244 in rats. Rats were exposed br iefly by inhalation to graded levels of monodisperse aerosols of (Cm2O 3)-Cm-244 heat-treated at 1150 degrees C. The initial lung burden (ILB ) of each animal was determined by the use of the gamma-ray-emitting r adionuclide Cm-243 in the aerosols. Seven groups of 84-day-old F344/Cr l rats (a total of 637 males and 645 females) were exposed once to (Cm 2O3)-Cm-244 or sham-exposed to filtered ambient air. Mean ILBs of all rats per group ranged from 0.51 +/- 0.17 (+/-SD) to 240 +/- 82 kBq kg( -1) body weight. Mean lifetime alpha-particle doses to the lungs per g roup ranged from 0.20 +/- 0.069 (+/-SD) to 36 +/- 6.5 Gy. After death, each rat was radiographed and necropsied. Dose-related increases occu rred in incidences of benign and malignant lung neoplasms, except for the groups of rats with higher mean ILBs that were examined histologic ally (98 +/- 18 and 240 +/- 77 kBq kg(-1) body weight) in which surviv al was markedly decreased. Also, average alpha-particle doses of 0.001 4 +/- 0.00058 (+/-SD) to 0.17 +/- 0.091 Gy and 0.018 +/- 0.007 to 1.6 +/- 1.1 Gy were also absorbed by the liver and skeleton, respectively, in the rats in the different exposure groups. Primary liver neoplasms occurred in several rats. However, the incidence of these lesions was not related to dose. Increased incidences of bone neoplasms occurred only in rats receiving higher doses to the skeleton. Excess numbers of rats with lung neoplasms per 10(4) Gy to the lung per group ranged fr om 760 +/- 430 (+/-SE) at a mean dose of 0.48 Gy to 84 +/- 16 at a mea n dose of 37 Gy. Risk factors for the lowest and highest ILB kg(-1) bo dy weight groups were not considered reliable because of large errors associated with these calculations and the life-span shortening in the highest ILB kg(-1) group. Inhaled (Cm2O3)-Cm-244 appeared to be about 50% less effective as a lung carcinogen in rats compared to (PuO2)-Pu -239 at similar doses. (C) 1997 by Radiation Research Society.