A Transformative Vision for an Omics-Based Regulatory Chemical Testing Paradigm.
A Transformative Vision for an Omics-Based Regulatory Chemical Testing Paradigm.
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DOI：
10.1093/toxsci/kfac097
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发表时间：
2022-11-23
期刊：
影响因子：
--
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中科院分区：
文献类型：
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科学界多年来一直期待在工业化学品和农用化学品的人类和生态健康风险评估中使用分子数据；然而，这些数据很少用于风险评估。在这里，提出了一个逻辑框架来探索转录组学方法的可行性和未来发展，以完善和取代当前基于顶端终点的监管毒性测试范式。概述并讨论了四项基本原则，在实现这一变革性愿景之前，利益相关者需要接受这些原则。在现有知识的充分支持下，首要原则是转录组学是检测由于测试生物体的内源性或外源性影响而导致的基因表达改变的可靠工具。第二个原则指出，基因表达的改变是生物体对应激源的不利或适应性生物反应的指标。原则 3 是转录组学可用于根据短期体内研究建立基于剂量的基准出发点 (POD)，剂量水平低于该水平时预计不会出现一致的分子变化 (CMC)。最后，原则 4 指出，转录组 POD（设定在 CMC 剂量水平）的使用将支持人类健康保护风险评估。如果所有四项原则都得到证实，这一愿景预计将改变工业化学品和农用化学品风险评估过程的各个方面，这些过程的重点是在众多毒理学背景下建立哺乳动物的安全暴露水平，从而显着减少动物使用，同时为人类健康提供同等或更大的保护。重要的是，这些原则和方法也普遍适用于生态安全评估。
Use of molecular data in human and ecological health risk assessments of industrial chemicals and agrochemicals has been anticipated by the scientific community for many years; however, these data are rarely used for risk assessment. Here, a logic framework is proposed to explore the feasibility and future development of transcriptomic methods to refine and replace the current apical endpoint-based regulatory toxicity testing paradigm. Four foundational principles are outlined and discussed that would need to be accepted by stakeholders prior to this transformative vision being realized. Well-supported by current knowledge, the first principle is that transcriptomics is a reliable tool for detecting alterations in gene expression that result from endogenous or exogenous influences on the test organism. The second principle states that alterations in gene expression are indicators of adverse or adaptive biological responses to stressors in an organism. Principle 3 is that transcriptomics can be employed to establish a benchmark dose-based point of departure (POD) from short-term, in vivo studies at a dose level below which a concerted molecular change (CMC) is not expected. Finally, Principle 4 states that the use of a transcriptomic POD (set at the CMC dose level) will support a human health-protective risk assessment. If all four principles are substantiated, this vision is expected to transform aspects of the industrial chemical and agrochemical risk assessment process that are focused on establishing safe exposure levels for mammals across numerous toxicological contexts resulting in a significant reduction in animal use while providing equal or greater protection of human health. Importantly, these principles and approaches are also generally applicable for ecological safety assessment.
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DOI：
10.1080/10937404.2010.483176
发表时间：
2010-02
期刊：
Journal of toxicology and environmental health. Part B, Critical reviews
影响因子：
--
作者：
Krewski D;Acosta D Jr;Andersen M;Anderson H;Bailar JC 3rd;Boekelheide K;Brent R;Charnley G;Cheung VG;Green S Jr;Kelsey KT;Kerkvliet NI;Li AA;McCray L;Meyer O;Patterson RD;Pennie W;Scala RA;Solomon GM;Stephens M;Yager J;Zeise L
通讯作者：
Zeise L
影响因子：
4.6
作者：
Harrill, Joshua;Shah, Imran;Thomas, Russell S.
通讯作者：
Thomas, Russell S.
影响因子：
4.3
作者：
Bianchi, Enrica;Costa, Eduardo;Johnson, Kamin J.
通讯作者：
Johnson, Kamin J.
影响因子：
3.8
作者：
Page-Lariviere, Florence;Crump, Doug;O'Brien, Jason M.
通讯作者：
O'Brien, Jason M.
影响因子：
3.8
作者：
Monticello, Thomas M.;Jones, Thomas W.;Kadambi, Vivek J.
通讯作者：
Kadambi, Vivek J.