Elucidating the Differences in Metal Toxicity by Quantitative Adverse Outcome Pathways,Environmental Science & Technology

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Elucidating the Differences in Metal Toxicity by Quantitative Adverse Outcome Pathways
Environmental Science & Technology ( IF 10.8 ) Pub Date : 2022-09-09 , DOI: 10.1021/acs.est.2c03828
Lanpeng Yang ₁ , Jing Zeng ₂ , Ning Gao ₁ , Lin Zhu ₁ , Jianfeng Feng ₁

Affiliation

Numerous studies have reported that the toxicity differences among metals are widespread; however, little is known about the mechanism of differences in metal toxicity to aquatic organisms due to the lack of quantitative understanding of their adverse outcome pathway. Here, we investigated the effects of Cd and Cu on bioaccumulation, gene expression, physiological responses, and apical effects in zebrafish larvae. RNA sequencing was conducted to provide supplementary mechanistic information for the effects of Cd and Cu exposure. On this basis, we proposed a quantitative adverse outcome pathway (qAOP) suitable for metal risk assessment of aquatic organisms. Our work provides a mechanistic explanation for the differences in metal toxicity where the strong bioaccumulation of Cu enables the newly accumulated Cu to reach the threshold that causes different adverse effects faster than Cd in zebrafish larvae, resulting in a higher toxicity of Cu than that of Cd. Furthermore, we proposed a parameter C_IT/BCF (the ratio of internal threshold concentration and bioaccumulation factor) that helps to understand the toxicity differences by combining the information of bioaccumulation and internal threshold of adverse effects. This work demonstrated that qAOP is an effective quantitative tool for understanding the toxicity mechanism and highlight the importance of toxicokinetics and toxicodynamics at different biological levels in determining the metal toxicity.

中文翻译：

通过定量不良结果途径阐明金属毒性的差异

许多研究报告说，金属之间的毒性差异很普遍。然而，由于缺乏对其不利结果途径的定量了解，人们对金属对水生生物的毒性差异机制知之甚少。在这里，我们研究了 Cd 和 Cu 对斑马鱼幼虫的生物积累、基因表达、生理反应和顶端效应的影响。进行 RNA 测序以提供关于 Cd 和 Cu 暴露影响的补充机制信息。在此基础上，我们提出了一种适用于水生生物金属风险评估的定量不良结果通路（qAOP）。我们的工作为金属毒性的差异提供了机制解释，其中 Cu 的强生物积累使新积累的 Cu 在斑马鱼幼虫中达到比 Cd 更快地引起不同不利影响的阈值，导致 Cu 的毒性高于 Cd . 此外，我们提出了一个参数C _IT /BCF（内部阈值浓度与生物蓄积因子之比），通过结合生物蓄积性和不良反应的内部阈值信息，有助于了解毒性差异。这项工作表明 qAOP 是一种有效的定量工具，可用于了解毒性机制，并强调不同生物学水平的毒代动力学和毒代动力学在确定金属毒性方面的重要性。

更新日期：2022-09-09

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