mittee used epidemiologic data to develop and quantify an empirical model of the exposure-risk relationship for lung-cancer. The committee did draw extensively, however, on findings from molecular, cellular, and animal studies in developing its risk assessment for the general population.
The committee's review of the cellular and molecular evidence was central to the specification of the risk model. This review led to the selection of a linear-nonthreshold relation between lung-cancer risk and radon exposure. However, the committee acknowledged that other relationships, including threshold and curvilinear relationships, cannot be excluded with complete confidence, particularly at the lowest levels of exposure. At low radon exposures, typical of those in homes, a lung epithelial cell would rarely be traversed by more than one alpha particle per human lifespan. As exposure decreases, the insult to cell nuclei that are traversed by alpha particles remains the same as at higher exposures, but the number of traversed nuclei decreases proportionally. There is good evidence that a single alpha particle can cause major genomic changes in a cell, including mutation and transformation. Even allowing for a substantial degree of repair, the passage of a single alpha particle has the potential to cause irreparable damage in cells that are not killed. In addition, there is convincing evidence that most cancers are of monoclonal origin, that is, they originate from damage to a single cell. These observations provide a mechanistic basis for a linear relationship between alpha-particle dose and cancer risk at exposure levels at which the probability of the traversal of a cell by more than one alpha particle is very small, that is, at exposure levels at which most cells are never traversed by even one alpha particle. On the basis of these mechanistic considerations, and in the absence of credible evidence to the contrary, the committee adopted a linear-nonthreshold model for the relationship between radon exposure and lung-cancer risk. However, the committee recognized that it could not exclude the possibility of a threshold relationship between exposure and lung-cancer risk at very low levels of radon exposure.
Extrapolation from higher to lower radon exposures is also influenced by the inverse dose-rate effect, an increasing effect of a given total exposure as the rate of exposure is decreased, as demonstrated by experiments in vivo and in vitro for high-LET radiation, including alpha particles, and in miner data. This dose-rate effect, whatever its underlying mechanism, is likely to occur at exposure levels at which multiple particle traversals per cell nucleus occur. Mechanistic, experimental, and epidemiologic considerations support the disappearance of the effect at low exposure corresponding to an average of much less than one traversal per cell location, as in most indoor exposures. Extrapolating radon risk from the full range of miner exposures to low indoor exposures involves extrapolating from a situation in which multiple alpha-particle traversals of target nuclei occur to one in which they are rare; such an extrapolation would be from circumstances in which the inverse dose-rate effect might be important to one in which it is likely to be nonexistent. These considerations indicated a need to assess risks of radon