Green T
ICI Central Toxicology Laboratory, Macclesfield, Cheshire, UK.
Ann Ist Super Sanita. 1991;27(4):595-9.
Attempts to improve quantitative risk assessments inevitably lead to the use of additional biological data in the risk calculation. The need for more data increases further when differences in response between laboratory animals result in uncertainty in the choice of either the species or the tumour incidence on which to base the risk assessment. Of the many stages of carcinogenesis, the first stage, which involves the uptake and activation of the chemical, is probably the most understood and is by far the easiest to measure experimentally. A review of the use of metabolism and pharmacokinetics in risk assessment reveals how this type of data can explain species differences, the shape of the dose-response curve and even determine the relevance of the animal carcinogenicity data to man. A number of chlorinated hydrocarbons are used to illustrate each of these points.
试图改进定量风险评估不可避免地会导致在风险计算中使用更多生物数据。当实验动物之间的反应差异导致在选择用于风险评估的物种或肿瘤发生率时存在不确定性时，对更多数据的需求会进一步增加。在致癌作用的多个阶段中，涉及化学物质摄取和活化的第一阶段可能是最容易理解的，并且是迄今为止最容易通过实验测量的。对代谢和药代动力学在风险评估中的应用进行的综述揭示了这类数据如何能够解释物种差异、剂量反应曲线的形状，甚至确定动物致癌性数据与人类的相关性。使用多种氯代烃来说明这些要点。
