Patlewicz G, Jeliazkova N, Safford R J, Worth A P, Aleksiev B
European Commission, DG Joint Research Centre, Institute for Health and Consumer Protection, Ispra, Italy.
SAR QSAR Environ Res. 2008;19(5-6):495-524. doi: 10.1080/10629360802083871.
Risk assessment for most human health effects is based on the threshold of a toxicological effect, usually derived from animal experiments. 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. When carefully applied, the TTC concept can provide a means of waiving testing based on knowledge of exposure limits. Two main approaches exist; the first of these is a General Threshold of Toxicological Concern; the second approach is a TTC in relation to structural information and/or toxicological data of chemicals. The structural scheme most routinely used is that of Cramer and co-workers from 1978. Recently this scheme was encoded into a software program called Toxtree, specifically commissioned by the European Chemicals Bureau (ECB). Here we evaluate two published datasets using Toxtree to demonstrate its concordance and highlight potential software modifications. The results were promising with an overall good concordance between the reported classifications and those generated by Toxtree. Further evaluation of these results highlighted a number of inconsistencies which were examined in turn and rationalised as far as possible. Improvements for Toxtree were proposed where appropriate. Notable of these is a necessity to update the lists of common food components and normal body constituents as these accounted for the majority of false classifications observed. Overall Toxtree was found to be a useful tool in facilitating the systematic evaluation of compounds through the Cramer scheme.
大多数对人类健康影响的风险评估是基于毒理学效应阈值，通常从动物实验得出。毒理学关注阈值（TTC）是一个概念，指的是为所有化学物质确定一个暴露水平，低于该水平对人类健康就不会有明显风险。谨慎应用时，TTC概念可以基于暴露限值知识提供一种免除测试的方法。存在两种主要方法；第一种是一般毒理学关注阈值；第二种方法是与化学物质的结构信息和/或毒理学数据相关的TTC。最常使用的结构方案是1978年克莱默及其同事提出的方案。最近，该方案被编码到一个名为Toxtree的软件程序中，该程序是由欧洲化学品管理局（ECB）专门委托开发的。在此，我们使用Toxtree评估两个已发表的数据集，以证明其一致性并突出潜在的软件修改。结果很有前景，报告的分类与Toxtree生成的分类总体上具有良好的一致性。对这些结果的进一步评估突出了一些不一致之处，我们依次对其进行了检查并尽可能做出了合理说明。在适当的地方提出了对Toxtree的改进建议。其中值得注意的是，有必要更新常见食物成分和正常身体成分的列表，因为这些导致了观察到的大多数错误分类。总体而言，发现Toxtree是通过克莱默方案促进化合物系统评估的有用工具。
