Threshold doses and circulatory disease risks.

Abstract

Tissue reactions (deterministic effects) become manifest either early or late after doses above a threshold dose, which is the basis for recommended dose limits for avoiding such effects. Threshold doses have been defined for comparative purposes at 1% incidence of an effect, although the choice of incidence level may be scenario-dependent in practice. Latency time before manifestation is related to cell turnover rates and tissue complexity. In general, threshold doses become lower for longer follow-up times because of the slow progression of injury before manifestation, particularly after lower doses. Radiosensitive individuals may contribute to low threshold doses, which would provide a safety margin for the majority of a population. A threshold dose of 0.5 Gy was proposed for radiation-induced circulatory disease, after acute or chronic exposures, in the International Commission on Radiological Protection Publication 118. However, more recent meta-analyses of low-dose population studies suggest that, if a linear dose-incidence is assumed, the risk of some types of circulatory disease after doses <0.5 Gy or <10 mGy day(-1) may be positive and similar to that for induced cancer. Animal studies show that doses >2 Gy induce the expression of inflammatory and thrombotic molecules in endothelial cells. This causes progressive loss of capillaries in the heart and leads to reduced perfusion, myocardial cell death, and fibrosis. However, doses <1 Gy inhibit both inflammatory cell adhesion to endothelial cells and the development of atherosclerosis in mice. Different mechanisms of injury at low and high doses preclude the simple extrapolation of risk on a linear-quadratic basis from acute to chronic exposures.