Cancer Risk Assessment with Intermittent Exposure

Applications of methods for carcinogenic risk assessment often focus on estimating lifetime cancer risk. With intermittent or time‐dependent exposures, lifetime risk is often approximated on the basis of a lifetime average daily dose (LADD). In this article, we show that there exists a lifetime equivalent constant dose (LECD)which leads to the same lifetime risk as the actual time‐dependent exposure pattern. The ratio C= LECD/LADD then provides a measure of accuracy of risk estimates based on the LADD, as well as a basis for correcting such estimates. Theoretical results derived under the classical multistage model and the two‐stage birth‐death‐mutation model suggest that the maximum value of C, which represents the factor by which the LADD may lead to underestimates of risk, will often lie in the range of 2‐ to 5‐fold. The practical application of these results is illustrated in the case of astronauts subjected to relatively short‐term exposure to volatile organics in a closed space station environment, and in the case of the ingestion of pesticide residues in food where consumption patterns vary with age.