Safford R J
Unilever Safety and Environmental Assurance Centre, Colworth Science Park, Sharnbrook, Bedford MK44 1LQ, UK.
Regul Toxicol Pharmacol. 2008 Jul;51(2):195-200. doi: 10.1016/j.yrtph.2008.02.010. Epub 2008 Mar 18.
The Threshold of Toxicological Concern (TTC) is a useful concept that is becoming of increasing interest as an addition to the arsenal of tools used for characterising the toxicological risk of human exposure to chemicals. Traditionally used for low level indirect additives, flavours and contaminants in foods, the TTC obviates the need for toxicological testing of chemicals where human exposure is low. Proposals have recently been made for the use of the TTC for low level ingredients in cosmetic and personal care products. However, use of the TTC is only protective for systemic toxicity endpoints, and cannot be used for local endpoints such as contact sensitisation. In this paper a probabilistic analysis of available sensitisation data, similar to that used in the development of the TTC, is presented. The incidence of sensitisers in the world of chemicals was estimated using the ELINCS (European List of Notified Chemical Substances) data set, and a distribution for sensitisation potency was established using a recently published compilation of Local Lymph Node Assay data. From the analysis of these data sets it is concluded that a Dermal Sensitisation Threshold (DST) can be established below which there is no appreciable risk of sensitisation, even for an untested ingredient. Use of a DST would preclude the need for sensitisation testing of ingredients where dermal exposure is sufficiently low.
毒理学关注阈值（TTC）是一个有用的概念，作为用于描述人类接触化学品的毒理学风险的工具库的补充，它正变得越来越受关注。TTC传统上用于食品中的低水平间接添加剂、香料和污染物，它消除了在人类接触水平较低的情况下对化学品进行毒理学测试的必要性。最近有人提议将TTC用于化妆品和个人护理产品中的低水平成分。然而，TTC的使用仅对全身毒性终点具有保护作用，不能用于局部终点，如接触性致敏。本文提出了一种对可用致敏数据的概率分析，类似于在TTC开发中使用的分析方法。利用欧洲现有商业化学物质清单（ELINCS）数据集估计了化学品世界中致敏剂的发生率，并利用最近发表的局部淋巴结试验数据汇编建立了致敏效力分布。通过对这些数据集的分析得出结论，可以确定一个皮肤致敏阈值（DST），低于该阈值，即使对于未经测试的成分，也不存在明显的致敏风险。使用DST将排除对皮肤接触足够低的成分进行致敏测试的必要性。
