TEMPORAL ASPECTS OF RISK CHARACTERIZATION

Although many laboratory studies are conducted with the dose level held constant for the duration of the experimental period, human exposure to toxic substances can vary widely over time. In this article we discuss methods for toxicologic risk assessment with time-dependent exposure patterns. In particular, methods for carcinogenic risk assessment under both the multistage and two-stage models are reviewed. It is shown that the use of a lifetime average daily dose or LADD can overestimate or underestimate the actual lifetime risk associated with time-dependent exposure patterns. II is also shown that there exists a lifetime equivalent constant dose or LECD that leads to the same lifetime risk as the actual time dependent exposure pattern. The ratio C = LADD/LECD thus provides a measure of accuracy of the LADD. Several applications are summarized to illustrate the application of currently available risk assessment methods for time-dependent exposures.