TEMPORAL ASPECTS OF RISK CHARACTERIZATION

Although many laboratory studies are conducted with the dose level hel d constant for the duration of the experimental period, human exposure to toxic substances can vary widely over time. In this article we dis cuss methods for toxicologic risk assessment with time-dependent expos ure patterns. In particular, methods for carcinogenic risk assessment under both the multistage and two-stage models are reviewed. It is sho wn that the use of a lifetime average daily dose or LADD can overestim ate or underestimate the actual lifetime risk associated with time-dep endent exposure patterns. II is also shown that there exists a lifetim e equivalent constant dose or LECD that leads to the same lifetime ris k as the actual time dependent exposure pattern. The ratio C = LADD/LE CD thus provides a measure of accuracy of the LADD. Several applicatio ns are summarized to illustrate the application of currently available risk assessment methods for time-dependent exposures.