利用综合毒物基因组学方法,开发以应激源为中心的塑料添加剂不良后果途径网络。

IF 4.8 2区 医学 Q1 TOXICOLOGY Archives of Toxicology Pub Date : 2024-08-03 DOI:10.1007/s00204-024-03825-z
Ajaya Kumar Sahoo, Nikhil Chivukula, Shreyes Rajan Madgaonkar, Kundhanathan Ramesh, Shambanagouda Rudragouda Marigoudar, Krishna Venkatarama Sharma, Areejit Samal
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引用次数: 0

摘要

由于塑料的广泛使用和环境持久性,塑料成为大气、陆地和水生生态系统中广泛存在的污染物。为了实现塑料的特定功能而有意添加的塑料添加剂会在塑料降解时渗入环境中,对生态和人类健康造成相当大的风险。由于对塑料添加剂在整个塑料生命周期中的存在了解有限,阻碍了对塑料添加剂的有效监管,从而给产品安全带来风险。在本研究中,我们利用不良后果途径(AOP)框架来了解塑料添加剂诱发毒性的机制。首先,我们从塑料中记录的化学物质中确定了一份包含 6470 种塑料添加剂的详尽清单。接下来,我们利用来自五个暴露相关资源的异质性毒物基因组学和生物终点数据,在 AOP-Wiki 中确定了 1287 种塑料添加剂与 322 个完整且高质量的 AOP 之间的关联。根据这些塑料添加剂与 AOP 的关联,我们构建了一个以应激源为中心的 AOP 网络,其中应激源被分为 10 个优先使用领域,而 AOP 则与 27 个疾病类别相关联。我们将 1287 种塑料添加剂中每一种添加剂的塑料添加剂-AOP 网络可视化,并将其公布在一个专门的网站上:https://cb.imsc.res.in/saopadditives/ 。最后,我们通过识别与苯并[a]芘 (B[a]P)、双酚 A (BPA) 和邻苯二甲酸二(2-乙基己基)酯 (DEHP) 相关的高度相关的 AOPs,展示了所构建的塑料添加剂-AOP 网络的实用性。总之,所构建的塑料添加剂-AOP 网络将有助于对塑料添加剂进行监管风险评估,从而为实现无毒塑料循环经济做出贡献。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Leveraging integrative toxicogenomic approach towards development of stressor-centric adverse outcome pathway networks for plastic additives

Plastics are widespread pollutants found in atmospheric, terrestrial and aquatic ecosystems due to their extensive usage and environmental persistence. Plastic additives, that are intentionally added to achieve specific functionality in plastics, leach into the environment upon plastic degradation and pose considerable risk to ecological and human health. Limited knowledge concerning the presence of plastic additives throughout plastic life cycle has hindered their effective regulation, thereby posing risks to product safety. In this study, we leveraged the adverse outcome pathway (AOP) framework to understand the mechanisms underlying plastic additives-induced toxicities. We first identified an exhaustive list of 6470 plastic additives from chemicals documented in plastics. Next, we leveraged heterogenous toxicogenomics and biological endpoints data from five exposome-relevant resources, and identified associations between 1287 plastic additives and 322 complete and high quality AOPs within AOP–Wiki. Based on these plastic additive–AOP associations, we constructed a stressor-centric AOP network, wherein the stressors are categorized into ten priority use sectors and AOPs are linked to 27 disease categories. We visualized the plastic additives–AOP network for each of the 1287 plastic additives and made them available in a dedicated website: https://cb.imsc.res.in/saopadditives/. Finally, we showed the utility of the constructed plastic additives–AOP network by identifying highly relevant AOPs associated with benzo[a]pyrene (B[a]P), bisphenol A (BPA), and bis(2-ethylhexyl) phthalate (DEHP) and thereafter, explored the associated toxicity pathways in humans and aquatic species. Overall, the constructed plastic additives–AOP network will assist regulatory risk assessment of plastic additives, thereby contributing towards a toxic-free circular economy for plastics.

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来源期刊
Archives of Toxicology
Archives of Toxicology 医学-毒理学
CiteScore
11.60
自引率
4.90%
发文量
218
审稿时长
1.5 months
期刊介绍: Archives of Toxicology provides up-to-date information on the latest advances in toxicology. The journal places particular emphasis on studies relating to defined effects of chemicals and mechanisms of toxicity, including toxic activities at the molecular level, in humans and experimental animals. Coverage includes new insights into analysis and toxicokinetics and into forensic toxicology. Review articles of general interest to toxicologists are an additional important feature of the journal.
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