Lifespan Studies in Rats Exposed to ²³⁹PuO₂ Aerosol. III. Survival and Lung Tumours

Abstract

Female, young adult, Wistar rat were given a single inhalation exposure to a submicron sized aerosol of high-fired ²³⁹PuO₂ and observed during their lifespan for primary lung tumours. Rats were distributed among sham-control (n = 1052) and exposed (n = 2105) groups. Survival was significantly reduced only in rat with lung doses > 30 Gy. A total of 99 primary lung tumours were found, of which 92% were malignant and 80% were carcinomas. Of malignant lung tumours, 49 were squamous cell carcinoma, 23 adenocarcinoma, nine hemangiosarcoma, seven adenosquamous carcinoma, and three fibrosarcoma. One adenocarcinoma was found in controls and only four adenomas were seen in the exposed rat at lung doses < 1·5 Gy. The lowest doses at which lung tumours appeared in exposed rats were 1·5 Gy for squamous cell carcinoma, 3·1 Gy for adenocarcinoma. 4·1 Gy for hemangiosarcoma, and about 9 Gy for adenosquamous carcinoma and fibrosarcoma. Pulmonary squamous metaplasia was not seen in controls and was first seen in exposed rats only at lung doses > 1 Gy. Primary lung tumours were the presumed cause of death (fatal) in 60% of rats with malignant lung tumours; causes of death were equally distributed among all tumour types and doses. The incidence of all lung tumours was 0·095% in control rats, 0·21% in 1877 rats with lung doses < 1 Gy, and 41% in 228 rats with doses > 1 Gy. Lung tumour incidence increased in a linear manner from 6·9% at 2·3 Gy to an incidence of 64–88% at 16–44 Gy. Absolute malignant lung tumour risk averaged 270 lung tumours per 10⁴ rat-Gy above a lung dose of 1 Gy. All types of malignant lung tumours induced by inhaled ²³⁹PuO₂ exhibited a threshold at a lung dose > 1 Gy.