Repeated inhalation exposure of rats to aerosols of 144CeO2. II. Effects on survival and lung, liver, and skeletal neoplasms

Abstract

Groups of 94-day-old F344/Crl rats were exposed repeatedly to aerosols of 144CeO2 to reestablish desired lung burdens of 1.9, 9.2, 46, or 230 kBq of 144Ce every 60 days for 1 year (seven exposures). Other 94-day-old rats were exposed once to achieve similar desired initial lung burdens of 144Ce. Older rats were exposed once to achieve desired initial lung burdens of 46 or 230 kBq when 500 days of age, the same age at which rats had the last of the repeated exposures. Control rats were either unexposed, sham-exposed once or repeatedly, or exposed once or repeatedly to stable CeO2. Approximately equal numbers of male and female rats were used. The median survival time and cumulative percentage survival curves were significantly decreased only in male and female rats exposed repeatedly to reestablish a 230-kBq lung burden and among the 94-day-old male rats exposed once to achieve a 230-kBq lung burden of 144Ce. The crude incidences of primary lung cancers (well described by a single Weibull distribution function), time to death with lung tumors, and risk of lung cancer per unit of beta-radiation dose to the lungs were correlated with the cumulative beta-radiation dose rather than the rate at which the dose was accumulated. A linear function, 70 (+/- 7.3) + -0.15 (+/- 0.056) x dose (+/- SD), adequately described the excess numbers of rats with lung cancers over a beta-radiation dose range to the lungs of 6.8 to 250 Gy for two groups of rats with the highest doses to the lungs after a single exposure and for two groups with the highest doses after repeated exposure.