Spatial stochasticity and correlated effects in dose–response relationships for environmental pollutants: a case study of radiation effects

Abstract.

 Models of dose–response for environmental pollutants generally do not include explicit consideration of the stochastic nature of the spatial pattern of dose delivered to an organ or tissue, or the correlation between events leading to a final health endpoint (such as cancer). The result can be significant errors in risk calculations when these stochastic properties contribute as strongly to the dose–response relationship as do the dose–response relationships for individual cells. The present paper considers the issue of stochasticity of dose and events (initiation, promotion and inactivation) for the case of carcinogenicity following exposure to environmental pollutants, using the case of irradiation by high LET emitters such as radon and progeny from water or air. The model is based on the concepts of hit probabilities and effect-specific track length probabilities (probability of damage per unit track length), and is applied first to in vitro data and then to predictions in vivo. It is shown that inhomogeneity of dose throughout an irradiated tissue or organ volume, and correlation between initiation, promotion and inactivation, can lead to significant differences in predicted risk.