Assessment of Risk from Short-Term Exposures

Abstract

One of the major problems encountered in cancer risk assessment is the estimation of risk for short-term exposures based upon results from chronic bioassays in which animals are exposed for a lifetime (generally two years for rodents). In the absence of data on cancer incidence for short-term exposures, the assumption is generally made that the cancer risk is proportional to the total accumulated dose (or equivalently, to the average dose rate) of a carcinogen, regardless of the ages at the times of exposures. This paper investigates the impact of using the total accumulated lifetime dose assumption to estimate cancer risk for short-term exposure for two carcinogenesis models, the Armitage-Doll multistage model and the Moolgavkar-Venzon-Knudson (M-V-K) birth-death mutation model. Two assumptions are discussed: (A) the fraction of lifetime dose rate assumes that the risk from a fractional lifetime exposure at a given dose rate is equal to the risk from full lifetime exposure at that same fraction of the given dose rate; and (B) the fraction of lifetime risk assumes that the risk from a fractional lifetime exposure at a given dose rate is equal to that same fraction of the risk from full lifetime exposure at the same dose rate. These two assumptions are equivalent when risk is a linear function of dose. Thus both can be thought of as generalizations of the assumption that cancer risk is proportional to the total accumulated lifetime dose.