In 1980, National Council on Radiation Protection and Measurements suggested the term dose-rate effectiveness factor (DREF) to describe the reduction of effectiveness of protracted radiation in producing biological damage and risk. A nonlinear decrease in damage was also noted following low total doses. The International Commission on Radiological Protection therefore combined the influence of low dose and low dose-rate and assigned a single value of 2.0 for a dose and dose-rate effectiveness factor (DDREF) to be applied for estimating risk for both low total dose and low dose-rate exposures. This paper re-evaluates one extensive data set on inhaled radionuclides in dogs which suggests that there may be a need to separate these factors (DREF and DDREF) for larger protracted doses from internally-deposited radioactive materials. Extensive recent research on the mechanisms of action of both low dose and low dose-rate radiation exposure at the molecular, cellular, and animal level of biological organization suggest that the influence of protraction of radiation may be large and variable, due to adaptive and protective responses, following very low doses and dose-rate exposures. Important observations in this paper in dogs exposed by inhalation to beta-gamma emitting radionuclides include (1) discontinuities in the data sets as a function of both dose and dose-rate suggesting shifts in mechanisms of action following high doses from protracted exposure away from those postulated for cancer from low total doses; (2) no increase in non-neoplastic disease, cancer frequency, or life-shortening following low dose-rate exposures to high total lung doses (up to 25 Gy); (3) all dogs that received doses below 25 Gy were combined and a decrease in the frequency of lung cancer in these exposed animals relative to the controls was noted, while very large doses from all radionuclides studied resulted in very marked increases in lung cancer; (4) a significant increase in hemangiosarcoma in the heart and tracheobronchial lymph nodes was observed after very high doses; (5) in this paper the DREF for lung cancer in dogs relative to single acute radiation exposure was as high as 35; and (6) the amount of life-shortening increased per unit dose as a function of the half-life with Y-90 being eight times as effective per unit of dose as Sr-90. Such information suggests that there may be a need to assign different values for DDREF and DREF, especially in situations where there are large nonuniform total doses delivered by internally-deposited radionuclides. This is extremely important since the risk from radiation exposure from internally-deposited radionuclides in the lungs following nuclear fallout, accidents and terrorist activities may be much less than currently projected. Health Phys. 97(5):458-469; 2009
