生物学交叉参照方法的基础和发展

The principle and development of biological based read-across method

传统交叉参照方法是基于化学结构相似性将化合物分组并构建毒理学预测模型。但由于毒性机制通常十分复杂,传统交叉参照方法的预测准确性不足,存在较大的不确定性,应用阈有限且难以对化学或生物学特征进行解释。因此需要在传统交叉参照方法的基础上,通过引入更多高质量的基于生物学的信息,如新技术方法(NAM)、有害结局路径(AOP)、基于生理药代动力学(PBPK)的模型以及代谢组学数据等,对交叉参照方法进行改进与发展,逐步将化学和生物学数据结合用于毒理学预测。本文主要对这些生物学信息,即生物学交叉参照的基础进行详细介绍与分析,介绍交叉参照发展的几种方式,包括传统交叉参照,“下一代”交叉参照和“生物学”交叉参照,并说明“生物学”交叉参照方法的优势与应用。

The typical read across(RA) is to group compounds based on the similarity of chemical structure and predict the property and toxicity of the target substance. However the accuracy of these prediction is usually insufficient and the uncertainty is relatively high due to the toxicological mechanism is complicated. Its application is limited and its biological characteristics is difficult to be demonstrated. Therefore it is imperative to introduce higher quality biolog-based information in the typical read across method, such as new approach methodology(NAM), adverse outcome pathway(AOP), physiological pharmacokinetics(PBPK) based models as well as metabolomics data. Chemical and biological data should be gradually combined for toxicological prediction. The principles of biological based read across are referred here, moreover, several read across approach including typical RA, next generation RA and biological RA, their virtue and development are introduced.