Carcinogenicity of radon/radon decay product inhalation in rats--effect of dose, dose rate and unattached fraction.
PURPOSE: The effects of inhalation of radon/radon decay products at different total doses, dose rates and 'unattached' fractions were investigated in a life span study in rats. MATERIALS AND METHODS: 1574 rats inhaled radon/radon decay products in a purpose-built recirculating exposure system that provided stable/reproducible exposure conditions. 501 were maintained as controls. RESULTS: Lung tumour incidences were significantly elevated in most exposed groups. The study power was insufficient to resolve the shape of the dose and dose rate response curves, but combination of this data with that from other studies demonstrated that for high cumulative exposures, the lifetime excess absolute risk increases with increasing exposure durations and for low cumulative exposures the opposite trend occurs. Exposure did not increase leukaemia incidences. A small number of non-lung tumour types including mammary fibroadenoma showed elevated incidences in some exposed groups, however not consistently across all exposure groups and showed no dose or dose rate relationship. CONCLUSIONS: Radon/radon decay product exposure caused excess lung tumours in rats along with limited non-lung effects. The results are consistent with the findings that at low cumulative exposures decreasing exposure concentrations or protracting the time over which the dose is delivered, reduces lung tumour risk. At higher levels, decreasing exposure concentrations or protracting exposure time increases lung tumour risk.