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应用“组学”技术进行化学品风险评估:欧洲化学生物学与毒理学中心研讨会报告。

Applying 'omics technologies in chemicals risk assessment: Report of an ECETOC workshop.

机构信息

BASF SE, Germany.

U.S. Environmental Protection Agency, USA.

出版信息

Regul Toxicol Pharmacol. 2017 Dec;91 Suppl 1(Suppl 1):S3-S13. doi: 10.1016/j.yrtph.2017.09.002. Epub 2017 Sep 25.

Abstract

Prevailing knowledge gaps in linking specific molecular changes to apical outcomes and methodological uncertainties in the generation, storage, processing, and interpretation of 'omics data limit the application of 'omics technologies in regulatory toxicology. Against this background, the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) convened a workshop Applying 'omics technologies in chemicals risk assessment that is reported herein. Ahead of the workshop, multi-expert teams drafted frameworks on best practices for (i) a Good-Laboratory Practice-like context for collecting, storing and curating 'omics data; (ii) the processing of 'omics data; and (iii) weight-of-evidence approaches for integrating 'omics data. The workshop participants confirmed the relevance of these Frameworks to facilitate the regulatory applicability and use of 'omics data, and the workshop discussions provided input for their further elaboration. Additionally, the key objective (iv) to establish approaches to connect 'omics perturbations to phenotypic alterations was addressed. Generally, it was considered promising to strive to link gene expression changes and pathway perturbations to the phenotype by mapping them to specific adverse outcome pathways. While further work is necessary before gene expression changes can be used to establish safe levels of substance exposure, the ECETOC workshop provided important incentives towards achieving this goal.

摘要

目前,将特定分子变化与顶端结果联系起来的知识空白,以及在‘组学’数据的生成、存储、处理和解释过程中存在的方法学不确定性,限制了‘组学’技术在监管毒理学中的应用。在此背景下,欧洲生态毒理学和化学毒物学中心(ECETOC)召开了一次研讨会,讨论了将‘组学’技术应用于化学品风险评估的问题,本文对此进行了报道。在研讨会之前,多专家小组起草了关于以下方面的最佳实践框架:(i) 类似于良好实验室规范的环境,用于收集、存储和管理‘组学’数据;(ii) ‘组学’数据的处理;以及 (iii) 整合‘组学’数据的证据权重方法。研讨会参与者确认了这些框架对于促进‘组学’数据的监管适用性和使用的相关性,并且研讨会讨论为进一步阐述这些框架提供了意见。此外,还解决了将‘组学’扰动与表型改变联系起来的关键目标 (iv)。一般来说,通过将它们映射到特定的不良结局途径,努力将基因表达变化和途径扰动与表型联系起来,这被认为是有前途的。虽然在可以将基因表达变化用于建立物质暴露的安全水平之前还需要做更多的工作,但 ECETOC 研讨会为实现这一目标提供了重要的动力。

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