Using the biological two-stage model to assess risk from short-term exposures

Two assumptions used in risk assessment are investigated: (1) the assumption of 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; (2) the assumption of 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 (or average daily dose), which is often made to assess the risk from short-term exposures. In this paper, the age-specific cumulative hazard functions are derived using the two-stage model developed by Moolgavkar, Venzon, and Knudson for situations when the exposure occurs during a single period or a single instant. The two assumptions described above are examined for three types of carcinogens, initiator, completer, and promoter, in the context of the model. For initiator and completer, these two assumptions are equivalent in the low-dose region; for a promoter, using the fraction of lifetime risk assumption is generally more conservative than that of the fraction of lifetime dose rate assumption. Tables are constructed to show that the use of either the fraction of lifetime dose rate assumption or the fraction lifetime risk assumption can both underestimate and overestimate the true risk for the three types of carcinogens.