Hartung Thomas
Center for Alternatives to Animal Testing (CAAT), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
CAAT-Europe, University of Konstanz, Germany.
ALTEX. 2017;34(3):331-351. doi: 10.14573/altex.1707011.
Low dose, low risk; very low dose, no real risk. Setting a pragmatic threshold below which concerns become negligible is the purpose of thresholds of toxicological concern (TTC). The idea is that such threshold values do not need to be established for each and every chemical based on experimental data, but that by analyzing the distribution of lowest or no-effect doses of many chemicals, a TTC can be defined - typically using the 5th percentile of this distribution and lowering it by an uncertainty factor of, e.g., 100. In doing so, TTC aims to compare exposure information (dose) with a threshold below which any hazard manifestation is very unlikely to occur. The history and current developments of this concept are reviewed and the application of TTC for different regulated products and their hazards is discussed. TTC lends itself as a pragmatic filter to deprioritize testing needs whenever real-life exposures are much lower than levels where hazard manifestation would be expected, a situation that is called "negligible exposure" in the REACH legislation, though the TTC concept has not been fully incorporated in its implementation (yet). Other areas and regulations - especially in the food sector and for pharmaceutical impurities - are more proactive. Large, curated databases on toxic effects of chemicals provide us with the opportunity to set TTC for many hazards and substance classes and thus offer a precautionary second tier for risk assessments if hazard cannot be excluded. This allows focusing testing efforts better on relevant exposures to chemicals.
低剂量，低风险；极低剂量，则无实际风险。设定一个实用的阈值，低于该阈值时相关担忧可忽略不计，这就是毒理学关注阈值（TTC）的目的。其理念是，无需基于实验数据为每种化学品确定此类阈值，而是通过分析许多化学品的最低无效应剂量分布，来定义一个TTC——通常使用该分布的第5百分位数，并通过例如100的不确定性系数对其进行下调。这样做时，TTC旨在将暴露信息（剂量）与一个阈值进行比较，低于该阈值时任何危害表现都极不可能发生。本文回顾了这一概念的历史和当前发展情况，并讨论了TTC在不同受监管产品及其危害方面的应用。每当实际生活中的暴露远低于预期会出现危害表现的水平时，TTC可作为一个实用的筛选工具，用于降低测试需求的优先级，在《化学品注册、评估、授权和限制法规》（REACH）中这种情况被称为“可忽略暴露”，不过TTC概念尚未完全纳入其实施过程。其他领域和法规——尤其是在食品行业和药品杂质方面——则更为积极主动。关于化学品毒性效应的大型、经过整理的数据库，为我们提供了为许多危害和物质类别设定TTC的机会，从而在无法排除危害时为风险评估提供一个预防性的第二层保障。这使得测试工作能够更好地聚焦于化学品的相关暴露。
