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Key read across framework components and biology based improvements.
Mutation Research/Genetic Toxicology and Environmental Mutagenesis ( IF 2.3 ) Pub Date : 2020-03-16 , DOI: 10.1016/j.mrgentox.2020.503172
Nicholas Ball 1 , Judith Madden 2 , Alicia Paini 3 , Miriam Mathea 4 , Andrew David Palmer 4 , Saskia Sperber 5 , Thomas Hartung 6 , Bennard van Ravenzwaay 5
Affiliation  

At the 2019 annual meeting of the European Environmental Mutagen and Genomics Society a workshop session related to the use of read across concepts in toxicology was held. The goal of this session was to provide the audience an overview of general read-across concepts. From ECHA’s read across assessment framework, the starting point is chemical similarity. There are several approaches and algorithms available for calculating chemical similarity based on molecular descriptors, distance/similarity measures and weighting schemata for specific endpoints. Therefore, algorithms that adapt themselves to the data (endpoint/s) and provide a good ability to distinguish between structural similar and not similar molecules regarding specific endpoints are needed and their use discussed. Toxico-dynamic end points are usually in the focus of read across cases. However, without appropriate attention to kinetics and metabolism such cases are unlikely to be successful. To further enhance the quality of read across cases new approach methods can be very useful. Examples based on a biological approach using plasma metabolomics in rats are given. Finally, with the availability of large data sets of structure activity relationships, in silico tools have been developed which provide hitherto undiscovered information. Automated process is now able to assess the chemical – activity space around the molecule target substance and examples are given demonstrating a high predictivity for certain endpoints of toxicity. Thus, this session provides not only current state of the art criteria for good read across, but also indicates how read-across can be further developed in the near future.



中文翻译:

跨框架组件和基于生物学的改进的关键阅读。

在欧洲环境诱变剂和基因组学学会 2019 年年会上,举行了一次有关在毒理学中使用跨概念阅读的研讨会。本次会议的目标是向观众提供一般通读概念的概述。从 ECHA 对评估框架的解读来看,起点是化学相似性。有多种方法和算法可用于基于分子描述符、距离/相似性度量和特定端点的加权模式计算化学相似性。因此,需要算法来适应数据(端点)并提供良好的能力来区分关于特定端点的结构相似和不相似的分子,并讨论了它们的使用。毒性动力学终点通常是跨病例阅读的重点。然而,如果不适当注意动力学和代谢,这种情况不太可能成功。为了进一步提高跨案例的阅读质量,新的方法可能非常有用。给出了基于在大鼠中使用血浆代谢组学的生物学方法的示例。最后,随着结构活动关系的大数据集的可用性,已开发出计算机工具,可提供迄今为止尚未发现的信息。自动化过程现在能够评估分子目标物质周围的化学活性空间,并且给出的例子证明了对某些毒性终点的高度预测性。因此,本次会议不仅提供了良好阅读的当前最先进标准,而且还表明了在不久的将来如何进一步发展阅读。

更新日期:2020-03-16
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