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; 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.

氟烷基物质（PFA）是全球关注的污染物的异源群。当前，特定的PFA所带来的风险，尤其是在陆地环境中，人们对此的理解很少。 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;与潜在的目标位点（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出新的毒性生理模型，这些模型可用于通过代表生命树的主要分支的不同陆地物种中的摄取模式和作用机理对PFA进行分类。现在，由于基因组可用性最近爆炸，增加的量表，增加的转录组和代谢性吞吐量以及生物固化的进步，在拟议的尺度上可以在拟议的尺度上进行雄心勃勃的目标与机械毒理学与机械毒理学联系起来。 3种分类学多样化的陆地物种。