有机化学品非动物替代风险评估组学研究进展
Advances in Omics Research for Risk Assessment of Non-animal Alternatives to Organic Chemicals
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摘要: 暴露评估是有机化学品风险评估的关键环节。准确评估有机化学品对动物或人体的危害程度能够有效降低其潜在风险。化学品风险评估的传统方法主要基于动物实验，然而相对于复杂的体内实验，体外细胞毒性实验具有经济、快速、易于量化和可重复的优势。基于人类细胞或细胞系的高通量检测和筛选方法，更有利于表征化学品的毒性效应，满足有机化学品管控的需求。随着生命科学步入后基因组学时代，研究的视角更加广泛，借助于基因组、转录组、蛋白质组、代谢组等组学工具，能够从基因表达的时空分布、蛋白质结构和功能的特性、蛋白质翻译后修饰以及代谢物的动态变化视角为化学品暴露风险评估提供多维度信息。本文从组学角度出发，系统地对近年来国内外有机化学品风险评估的研究进展、组学的研究策略以及组学在有机化学品风险评估中的应用进行了综述和展望，提出组学的联合应用将更加系统全面地探究化学品毒性机制，为我国非动物替代有机化学品暴露风险评估提供技术指引和参考。Abstract: Exposure assessment serves as a pivotal component in the risk evaluation of organic chemicals. Precise evaluation of the potential hazards posed by these chemicals to animals or humans is essential for effectively mitigating their associated risks. Traditional approaches to chemical risk assessment have traditionally relied on animal studies. However, in vitro cytotoxicity experiments present distinct advantages, such as economic efficiency, rapid execution, ease of quantification, and reproducibility, when compared to intricate in vivo experiments. Quantitative automated high-throughput assays, particularly those employing human cells or cell lines, prove advantageous in delineating the toxic effects of chemical substances and addressing the regulatory requirements for controlling organic chemicals. As life sciences transition into the post-genomics era, research perspectives have been broadened. Leveraging omics tools like genomics, transcriptomics, proteomics, and metabolomics enables the provision of multi-dimensional insights for chemical exposure risk assessment. These insights encompass spatial and temporal distributions of gene expression, properties of protein structure and function, post-translational modifications of proteins, and dynamic changes in metabolites. This review systematically examines and outlines recent advancements in organic chemical risk assessment at both domestic and international levels. The review underscores the research strategy of omics and explores its application in organic chemical risk assessment, providing a comprehensive perspective. It is suggested that the collaborative application of omics methodologies will facilitate a more systematic and comprehensive exploration of the toxicity mechanisms of chemicals. Furthermore, this review puts forth technical guidelines and references to support the risk assessment of exposure to non-animal substitute organic chemicals in China.
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Key words:
- organic chemical substances /
- in vitro risk assessment /
- toxicity test /
- omics techniques
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