传统毒理学理论认为,有毒物质产生毒害作用的剂量-效应关系是线性单调的,线性剂量-效应关系也是目前管理毒理学中计算化学品安全剂量的理论基础。但越来越多的研究显示,内分泌干扰物的剂量-效应关系通常不是线性的,而是U型、倒U型或更复杂的非单调剂量-效应曲线形式。以典型案例的形式介绍了近年来生理激素和内分泌干扰物非单调剂量-效应的研究进展,总结了目前认为形成非单调剂量-效应关系的机制。在此基础上,讨论了内分泌干扰物的非单-剂量-效应给目前管理毒理学中的化学品风险评价带来的挑战,并提出该领域未来的研究方向。
In traditional toxicology theory, the dose-response relationship caused by toxicants is linear and monotonic. Linear dose-response relationship is the theoretical base for calculating the safe dose of chemicals. However, more and more studies have shown that dose-responses of endocrine disruptors are non-linear, i.e. U-shaped, inverted U-shaped or more complicated non-monotonic dose-response curves. We introduced the research progress in non-monotonic dose-response of hormones and endocrine disruptors by illustrating typical examples and summa- rized several mechanisms for non-monotonic dose-response. Then, we discussed the challenges that non-monotonic dose-response brings to risk assessment for chemicals in traditional regulatory toxicology.