Murdoch D J, Krewski D, Wargo J
Department of Statistics and Actuarial Science, University of Waterloo, Kingston, Ontario, Canada.
Risk Anal. 1992 Dec;12(4):569-77. doi: 10.1111/j.1539-6924.1992.tb00713.x.
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.
致癌风险评估方法的应用通常侧重于估计终生癌症风险。对于间歇性或随时间变化的暴露情况，终生风险通常基于终生平均每日剂量（LADD）进行近似估算。在本文中，我们表明存在一个终生等效恒定剂量（LECD），它导致的终生风险与实际随时间变化的暴露模式相同。比值C = LECD/LADD随后提供了基于LADD的风险估计准确性的一种度量，以及校正此类估计的基础。在经典多阶段模型和两阶段出生-死亡-突变模型下得出的理论结果表明，C的最大值（代表LADD可能导致风险低估的因子）通常在2至5倍的范围内。这些结果在以下两种情况下得到了实际应用：一是宇航员在封闭的空间站环境中受到相对短期的挥发性有机物暴露；二是在食物中摄入农药残留的情况，其中消费模式随年龄变化。
