Dose Responses from Inhaled Monodisperse Aerosols of 244 Cm2 O3 in the Lung, Liver and Skeleton of F344 Rats and Comparison with 239 PuO2

The purpose of this study was to obtain information on the α-particle dose-response relationship of ^{244}{\rm Cm}$ in rats. Rats were exposed briefly by inhalation to graded levels of monodisperse aerosols of 244 Cm2 O3 heat-treated at 1150°C. The initial lung burden (ILB) of each animal was determined by the use of the γ-ray-emitting radionuclide ^{243}{\rm Cm}$ in the aerosols. Seven groups of 84-day-old F344/Crl rats (a total of 637 males and 645 females) were exposed once to 244 Cm2 O3 or sham-exposed to filtered ambient air. Mean ILBs of all rats per group ranged from 0.51 ± 0.17 (±SD) to $240\pm 82\ {\rm kBq}\ {\rm kg}^{-1}$ body weight. Mean lifetime α-particle doses to the lungs per group ranged from 0.20 ± 0.069 (±SD) to 36 ± 6.5 Gy. After death, each rat was radiographed and necropsied. Dose-related increases occurred in incidences of benign and malignant lung neoplasms, except for the groups of rats with higher mean ILBs that were examined histologically (98 ± 18 and $240\pm 77\ {\rm kBq}\ {\rm kg}^{-1}$ body weight) in which survival was markedly decreased. Also, average α-particle doses of 0.0014 ± 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 104 Gy to the lung per group ranged from 760 ± 430 (±SE) at a mean dose of 0.48 Gy 84 ± 16 at a mean dose of 37 Gy. Risk factors for the lowest and highest ${\rm ILB}\ {\rm kg}^{-1}$ body weight groups were not considered reliable because of large errors associated with these calculations and the life-span shortening in the highest ${\rm ILB}\ {\rm kg}^{-1}$ group. Inhaled 244 Cm2 O3 appeared to be about 50% less effective as a lung carcinogen in rats compared to 239 PuO2 at similar doses.