Butterworth B E, Eldridge S R
Chemical Industry Institute of Toxicology, (CIIT), Research Triangle Park, NC 27709, USA.
Prog Clin Biol Res. 1995;391:49-70.
When presented with the information that an environmental chemical produces cancer in animals, the default approach is to apply the linearized multistage risk model with no mechanistic information. The decision tree presented here outlines a straightforward strategy in the collection of information relevant to risk assessment. Three situations are noted where a different approach to risk assessment should be considered: (1) a tumor response that is not relevant to the human situation; (2) chemicals acting through a nongenotoxic/cytotoxic mode of action; and (3) chemicals acting through a nongenotoxic/mitogenic mode of action. Usually upon learning that a chemical produced a rodent tumor response, no additional research is done because of the high costs in money, time, and personnel to conduct such studies. Compounding this situation is a widely-held view that no amount of mechanistic information will be sufficient to convince regulators to depart from the default risk assessment. Hence, there are very few data sets to confirm and refine the above suggestions. There should be incentives to conduct the research required to obtain the type of information outlined in the decision tree approach presented here. All involved with these issues agree that the gathering and use of scientific information should be encouraged. Hopefully, these suggestions will provide a means of furthering that goal.
当得知一种环境化学物质会在动物身上引发癌症时，默认的方法是在没有机理信息的情况下应用线性化多阶段风险模型。此处给出的决策树概述了一种收集与风险评估相关信息的直接策略。文中指出了三种应考虑采用不同风险评估方法的情况：（1）与人类情况无关的肿瘤反应；（2）通过非遗传毒性/细胞毒性作用模式起作用的化学物质；（3）通过非遗传毒性/促有丝分裂作用模式起作用的化学物质。通常，一旦得知一种化学物质会引发啮齿动物的肿瘤反应，由于开展此类研究在资金、时间和人力方面成本高昂，就不会再进行额外的研究。使这种情况更为复杂的是一种普遍的观点，即再多的机理信息也不足以说服监管机构背离默认的风险评估。因此，几乎没有数据集可用于证实和完善上述建议。应该鼓励开展所需的研究，以获取此处提出的决策树方法中概述的那种信息。所有涉及这些问题的人都同意应鼓励收集和使用科学信息。希望这些建议将为推进这一目标提供一种途径。
