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.
Murdoch
D J
DJ
Department of Statistics and Actuarial Science, University of Waterloo, Kingston, Ontario, Canada.
Krewski
D
D
Wargo
J
J
D000328:Adult; D000818:Animals; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic; D002648:Child; D006801:Humans; D007223:Infant; D008954:Models, Biological; D015233:Models, Statistical; D009369:Neoplasms / Q000139:chemically induced*; D009374:Neoplasms, Experimental / Q000139:chemically induced; D010575:Pesticides / Q000009:adverse effects; D012307:Risk Factors; D013026:Space Flight
D002273:Carcinogens; D010575:Pesticides