PULMONARY CARCINOGENICITY OF REPEATED INHALATION EXPOSURE OF RATS TO AEROSOLS OF (PUO2)-PU-239

To study the long-term biological effects of repeated inhalation expos ure to (PuO2)-Pu-239, 84-day-old rats were exposed to aerosols of (PuO 2)-Pu-239 to re-establish desired Pu-239 lung burdens of 26, 80 or 250 Bq every other month for 1 year (seven exposures). Other rats were ex posed once at 84 or 450 days of age to achieve desired initial lung bu rdens of 30, 90, 280 or 850 Bq. The incidences of lung tumors were not significantly different (Fisher's exact test; P > 0.05) in groups of rats with similar lifetime mean alpha-particle doses to the lungs of 0 .90 +/- 0.39 to 4.4 +/- 1.8 (+/- SD) Gy, whether exposed once or repea tedly. Among rats with mean alpha-particle doses of 12 +/- 2.4 to 10 /- 2.1 Gy to the lungs after single or repeated exposures, respectivel y, the crude incidence of lung tumors was significantly less (Fisher's exact test; P < 0.05) in the rats exposed repeatedly. Times to death of rats with lung tumors were compared among groups with similar alpha -particle doses to the lungs after single or repeated exposure to (PuO 2)-Pu-239. Those that died with lung tumors after repeated exposures d ied at times similar to (Mantel-Cox statistic; P > 0.05) or later than (Mantel-Cox statistic; P < 0.05) those for 84-day-old rats exposed on ce. The risk of lung tumors in rats per unit dose to the lungs was les s in the rats exposed repeatedly than in those exposed once. It was co ncluded that a-particle doses to the lung of rats exposed repeatedly t o aerosols of (PuO2)-Pu-239 were not more carcinogenic and possibly we re less carcinogenic than the dose after a single inhalation exposure when rats with similar lifetime alpha-particle doses to the lungs were compared. The relative biological effectiveness in rats of the alpha- particle dose to the lungs from inhaled (PuO2)-Pu-239 relative to beta -particle doses to the lungs from inhaled (CeO2)-Ce-144 was 21 +/- 3. (C) 1995 by Radiation Research Society