Genotoxic impurities: the new ICH M7 addendum to calculation of compound-specific acceptable intakes
基因毒性杂质：新的ICH M7增补化合物特定可接受摄入量的计算
The final document of the ICH-Guideline M7 was published in June 2014. It describes the procedure for evaluating the genotoxic potential of impurities in medicinal products (see also our news Final ICH M7 Guideline on Genotoxic Impurities published dated 23 July 2014).
2014年6月ICH公布了ICH 指南M7最终版本。其中描述了评估药品中杂质的潜在基因毒性的程序（参见我们2014年7月23日的新闻“ICH M7指南基因毒性杂质公布”）。
An important approach to the risk characterisation of impurities is the TTC concept (TTC = threshold of toxicological concern). According to this approach the exposure to a mutagenic impurity having the concentration of 1.5 ?g per adult person per day is considered to be associated with a negligible risk. It can be used as default evaluation approach to most pharmaceuticals for long-term treatment (> 10 years) and where no carcinogenicity data are available (classes 2 and 3). According to ICH M7 the TTC concept should not be used where sufficient carcinogenicity data exist. Instead the data should be used to calculate or derive compound-specific acceptable intakes.
对杂质风险属性进行评估的一个重要方法是TTC概念（TTC=毒性关注阈值）。根据该方法，暴露于1.5ug/成人/天浓度的诱变性杂质被认为是可以忽略的风险。它可以作为默认的评估方式，用于大多数长期治疗用的药品（长于10年），并且没有致癌性数据可以获得时（二类和三类）。根据ICH M7，如果有足够的致癌数据存在的话，则不应该使用TTC概念。这时应该使用这些数据来计算或推导化合物特定的可接受摄入量。
Now the ICH published an addendum to Guideline M7 with the title "Application of the principles of the ICH M7 Guideline to calculation of compound-specific acceptable intakes" ("Addendum to ICH M7"; short name "M7(R1)").
现在ICH公布了指南M7的增补，题为“ICH M7化合物特定可接受摄入量计算指南的应用原则”（ICH M7增补，简称为M7(R1)）。
This addendum describes the basis for calculating the acceptable intakes for 15 substances in total that are common and widespread in pharmaceutical manufacturing. These substances are known to have mutagenic/carcinogenic potential (ICH M7(R1) contains comprehensive references on the toxicology of these substances). The calculations of the AI (acceptable intake) or PDE (permitted daily exposure) values are partly based on a linear extrapolation from the TD50 values as well as on toxicological data on the non-linear dose-response curve of the relevant substances.
该增补描述了共15个物质可接受摄入量的计算基础，这些物质在药品生产中较为常见并广泛分布。众所周知这些物质具有潜在诱变性/致癌性（ICH M7(R1)包括了对这些物质毒理学文献的综合引用）。AI（可接受标准）或PDE（允许日暴露量）值的计算部分基于从相关物质TD50值，以及非线性剂量-反应曲线的毒理学数据线性外推。
ICH M7(R1) has the status of a draft consensus guideline (step 2 document). The draft guideline was published on the EMA "Scientific Guidelines" site as step 2b document on 4 August 2015 for consultation (deadline for comments: 3 February 2016).
ICH M7(R1)现在是达成一致的草案指南（第二阶段文件）。指南草案于2015年8月4日公布在EMA“科学指南网址”上作为“第2b阶段文件”征求公众意见（截止时间2016年2月3日）。
