To study the long-term biological effects of repeated inhalation exposure to239 PuO2, 84-day-old rats were exposed to aerosols of239 PuO2 to re-establish desired239 Pu lung burdens of 26, 80 or 250 Bq every other month for 1 year (seven exposures). Other rats were exposed once at 84 or 450 days of age to achieve desired initial lung burdens 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 α-particle doses to the lungs of 0.90 ± 0.39 to 4.4 ± 1.8 (± SD) Gy, whether exposed once or repeatedly. Among rats with mean α-particle doses of 12 ± 2.4 to 10 ± 2.1 Gy to the lungs after single or repeated exposures, respectively, 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 α-particle doses to the lungs after single or repeated exposure to239 PuO2. Those that died with lung tumors after repeated exposures died 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 once. The risk of lung tumors in rats per unit dose to the lungs was less in the rats exposed repeatedly than in those exposed once. It was concluded that α-particle doses to the lung of rats exposed repeatedly to aerosols of239 PuO2 were not more carcinogenic and possibly were less carcinogenic than the dose after a single inhalation exposure when rats with similar lifetime α-particle doses to the lungs were compared. The relative biological effectiveness in rats of the α-particle dose to the lungs from inhaled239 PuO2 relative to β-particle doses to the lungs from inhaled${}^{144}{\rm CeO}{}_{2}$ was 21 ± 3.

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