毒理学关注阈值(TTC)方法的历史演化与发展

Historical Evolution and Development of the Threshold (TTC) of Toxicological Concern

毒理学关注阈值(TTC)的概念是指,对化学品建立一个人体暴露阈值,当低于该阈值时化学品对人体健康无明显的风险。TTC方法从提出至今已将近半个世纪,并经历了一个不断完善和发展的过程。本文主要从TTC方法的建立、发展、改进等方面进行了探讨。TTC方法最初被用于食品接触材料中安全阈值的确定。之后,人们对经口的非致癌毒性终点的无明显作用剂量(NOEL)进行了分析,发展出了以结构类为基础的多层次TTC方法。这种以结构类为基础的多层次TTC方法后来被联合国粮农组织/世界卫生组织(FAO/WHO)食品添加剂联合专家委员会(JECFA)和欧洲食品安全局(EFSA)等组织所采用,并在此基础上进行了发展和改进。TTC方法现已经在低人体暴露水平的化学物质风险评估中得到了广泛的应用,避免了大量不必要的,过于详细的研究,以及广泛的毒理学实验。TTC方法也为那些用量极低并且缺乏完整毒性数据的化学物质的风险评估提供了一条可行的途径。

The threshold of toxicological concern （TTC） is a concept that refers to the establishment of a level of exposure for all chemicals, below which there would be no appreciable risk to human health. The TTC method has been applied for nearly half a century since it was proposed, and has experienced a continuous improvement and development process. The establishment, development and improvement of TTC method were discussed. TTC method was originally developed to determine the threshold of safety in food materials. Since then, the non-carcinogenic oral toxicity endpoint of no significant effect level （NOEL） was analyzed to develop a structural class-based multi-scale TTC which was then adopted by Food Additives of FAO/World Health Organization （FAO/WHO） Joint Expert Committee （JECFA） and the European Food Safety Authority （EFSA） with development and improvement. The TTC approach is in wide application to assess the risk of chemicals at low exposure levels, which avoids multiple unnecessary, overly detailed studies, as well as a wide range of toxicological experiments. The TTC method also provides a feasible way for the risk assessment of chemical substances that the amount is very low but lack of a complete toxicity data.