Renwick A G
Allergy and Inflammatory Sciences Research Division, School of Medicine, University of Southampton, Biomedical Sciences Building, Bassett Crescent East, Southampton SO16 7PX, UK.
Toxicol Appl Pharmacol. 2005 Sep 1;207(2 Suppl):585-91. doi: 10.1016/j.taap.2005.01.034.
Health-based guidance values, such as the ADI, use chemical-specific data to determine the highest intake that would be without significant adverse health effects. A threshold of toxicological concern (TTC) is a level of intake predicted to be without adverse effects based on the toxicity of structurally related compounds. The main advantage of the use of TTCs is that the risk of low exposures can be evaluated without the need for chemical-specific animal toxicity data. TTCs have been used for many years for screening the safety of packaging migrants by the FDA in the USA, and of flavoring substances, by the JECFA. A recent reassessment of the use of TTCs, organized by ILSI Europe, has developed a decision tree which allows a systematic approach to the evaluation of low levels of diverse chemicals in food. The decision tree incorporates a series of increasing TTC values into a step-wise approach. Potentially genotoxic carcinogens are considered first, based on the presence of known structural alerts. Aflatoxin-like, azoxy- and nitroso-compounds are removed from consideration because they are the most potent, and a practical TTC could not be established. Other compounds with structural alerts for genotoxicity are allocated a TTC of 0.15 microg/person per day. Compounds without structural alerts for genotoxicity are evaluated based on chemical structure and intake using a series of TTC values derived by the application of a 100-fold uncertainty factor to the 5th percentile of the distribution of NOAELs from chronic studies on compounds sharing similar structural characteristics.
基于健康的指导值，如每日允许摄入量（ADI），利用特定化学物质的数据来确定在无显著健康不良影响情况下的最高摄入量。毒理学关注阈值（TTC）是基于结构相关化合物的毒性预测无不良影响的摄入量水平。使用TTC的主要优点是无需特定化学物质的动物毒性数据即可评估低暴露风险。在美国，美国食品药品监督管理局（FDA）多年来一直使用TTC筛查包装迁移物的安全性；在国际食品添加剂联合专家委员会（JECFA）方面，TTC用于调味物质的安全性筛查。欧洲国际生命科学研究所（ILSI Europe）组织的近期对TTC使用的重新评估，开发了一种决策树，可采用系统方法评估食品中多种低水平化学物质。该决策树将一系列递增的TTC值纳入逐步评估方法。首先根据已知结构警示物的存在情况考虑潜在的遗传毒性致癌物。黄曲霉毒素样、氧化偶氮和亚硝基化合物因毒性最强而被排除在考虑范围之外，无法确定实际的TTC。其他具有遗传毒性结构警示物的化合物被分配的TTC为每人每天0.15微克。对于无遗传毒性结构警示物的化合物，根据化学结构和摄入量进行评估，使用的一系列TTC值是通过将100倍不确定系数应用于对具有相似结构特征的化合物进行慢性研究得出的无观察到不良作用水平（NOAEL）分布的第5百分位数而推导出来的。
