Szymczak W
Zakładu Epidemiologii Srodowiskowej, Instytutu Medycyny Pracy im. prof. dra med. Jerzego Nofera w Lodzi.
Med Pr. 1998;49(6):579-87.
The characteristics of the relationship between the exposure level and the incidence of harmful health effects is a general objective of assessing health risk related to chemical exposure. A real dose-response relationship, particularly for low doses, is usually unknown thus it can only be deduced on the basis of biological and statistical considerations. Low dose risk estimation requires extrapolation beyond the range of data observed. Nowadays, quantitative risk assessment encounters certain duality as linear models are mostly used in evaluation of environmental exposure, and nonlinear models are most frequently applied in occupational exposure. Bearing in mind that the assumption on the dose-response linear relationship is an apparent simplification built on our lack of knowledge of carcinogenic mechanisms, it seems that the proposal of the US Environmental Protection Agency (US EPA) to use benchmark dose methods (BMD) for exposure effects manifested by neoplasms, is the compromise between a conservative approach of the EPA towards risk modelling resulting from the limited knowledge of these mechanisms and lack of criteria for selection of nonlinear models. In the case of carcinogenic risk assessment, this solution involves the identification of so called 'cut off point' by applying relevant statistical models. The cut off point indicates the exposure level that contributes to the increase in risk by 10%, 5% or 1%. Another possibility is to use interspecies extrapolation methods for the cut of point modification, and then draw a line between the cut off point and the beginning of the system of co-ordinates. Since it is not feasible to apply a complete BMD methods for certain chemicals (e.g. bezo(a)pirene), not because of chemical properties, but due to insufficient experimental experience, it is proposed to use the method of sticking together a straight line and a curve in relation to a two-grade curve and not to its confidence limitation.
暴露水平与有害健康影响发生率之间关系的特征是评估与化学物质暴露相关的健康风险的总体目标。真正的剂量-反应关系，尤其是低剂量的关系，通常是未知的，因此只能基于生物学和统计学考量来推断。低剂量风险评估需要在观察到的数据范围之外进行外推。如今，定量风险评估面临一定的二元性，因为线性模型大多用于环境暴露评估，而非线性模型则最常用于职业暴露评估。鉴于剂量-反应线性关系的假设显然是基于我们对致癌机制缺乏了解而做出的简化，美国环境保护局（US EPA）提议对肿瘤表现出的暴露效应使用基准剂量方法（BMD），这似乎是EPA在因对这些机制了解有限以及缺乏非线性模型选择标准而采取的保守风险建模方法之间的一种折衷。在致癌风险评估中，这种解决方案涉及通过应用相关统计模型来确定所谓的“临界点”。临界点表明导致风险增加10%、5%或1%的暴露水平。另一种可能性是使用种间外推方法来修改临界点，然后在临界点与坐标系起点之间画一条线。由于对某些化学物质（如苯并(a)芘）应用完整的BMD方法不可行，不是因为化学性质，而是由于实验经验不足，建议使用将直线和曲线粘合成二级曲线而非其置信区间的方法。
