Simply forever: Tackling PFAS complexity through mode of action assignment

永远简单：通过行动模式分配解决 PFAS 复杂性

• 批准号: NE/Z000084/1
• 负责人: David Spurgeon
• 金额: $ 121.62万
• 依托单位: UK CENTRE FOR ECOLOGY & HYDROLOGY
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=NE%2FZ000084%2F1
• 关键词: Simply; forever; Tackling; PFAS; complexity

Per- and poly-fluoroalkyl substances (PFAS) are a heterogenous group of contaminants of global concern. Currently, the risks posed by specific PFAS, especially in terrestrial environments, are poorly understood. Weak correlations between structure, chemical properties and toxicological effects (which may limit read-across and the use of QSARs) means new approaches are needed that can identify the more hazardous PFAS and further can support grouping for exposure and hazard assessment.Working with 3 phylogenetically distant terrestrial taxa, we will study how 16 carefully selected PFAS from four classes bioaccumulate; interact with potential target sites (e.g. PPAR and other receptors), and how such interactions disrupt gene expression networks and metabolic systems. This integrated analysis will allow us to develop new physiological models of toxicity that can be used to classify PFAS by uptake patterns and mechanisms of action in different terrestrial species representing major branches of the tree of life. The ambitious objective of linking exposure and uptake with mechanistic toxicology at the gene and metabolite level is now tractable at the proposed scale due to the recent explosion of genome availability, increased transcriptomic and metabolomic throughput and advances in biostatistics.In this project we will develop a mechanism of action based compound grouping for PFAS by integrating the transcriptomic, metabolic, cellular and apical effects of exposure on 3 taxonomically diverse terrestrial species.

全氟烷基物质和多氟烷基物质 (PFAS) 是全球关注的一组异质污染物。目前，人们对特定 PFAS 带来的风险（尤其是在陆地环境中）知之甚少。结构、化学性质和毒理学效应之间的弱相关性（这可能会限制 QSAR 的读取和使用）意味着需要新的方法来识别更危险的 PFAS，并进一步支持暴露和危害评估的分组。在系统发育上使用 3对于遥远的陆地类群，我们将研究从四个类别中精心挑选的 16 种 PFAS 如何进行生物累积；与潜在靶位点（例如 PPAR 和其他受体）相互作用，以及这种相互作用如何破坏基因表达网络和代谢系统。这种综合分析将使我们能够开发新的毒性生理模型，可用于根据代表生命之树主要分支的不同陆地物种的吸收模式和作用机制对 PFAS 进行分类。由于最近基因组可用性的爆炸性增长、转录组学和代谢组学通量的增加以及生物统计学的进步，将暴露和摄取与基因和代谢物水平的机械毒理学联系起来的雄心勃勃的目标现在可以在拟议的规模上实现。通过整合暴露对 3 个分类学不同的陆地物种的转录组、代谢、细胞和顶端效应，对 PFAS 进行基于作用机制的化合物分组。