Discovery Exposomics by Non-Targeted Identification of Organic Contaminants in Human and Environmental Samples

通过非靶向鉴定人类和环境样本中的有机污染物来发现暴露组学

• 批准号: RGPIN-2016-06487
• 负责人: Martin, Jonathan
• 金额: $ 4.45万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=632569
• 关键词: Discovery; Exposomics; Non; Targeted; Identification

Most organic contaminants, including those classified internationally as “persistent organic pollutants” (POPs), were only discovered in the environment after several decades of intense use. This long delay in discovery was a result of the traditional reliance on targeted analytical methods, which are often limited by lack of authentic chemical standards. Through my NSERC Discovery research program I will develop powerful screening techniques to identify new contaminants in a non-targeted fashion. In other words, I aim to discover important contaminants without any previous knowledge that they are there. A “discovery exposomic” workflow has been proposed that includes sensitive sample preparation techniques coupled to a battery of powerful instrumental methodologies capable of separating and identifying trace unknowns that are potentially bioaccumulative, persistent and toxic. Large-volume stir-bar sorptive extraction (SBSE) methods will be developed for fractionation of the hydrophobic (bioaccumulative) and polar fractions of human blood and urine, and oxidation tests will be used to identify the most persistent unknown chemicals. We will validate three analytical methods to analyze the sample fractions, including by HPLC and high-efficiency supercritical fluid chromatography linked to ultrahigh resolution mass spectrometry operating in full scan and with unique flagging modes designed to detect halogenated chemicals and toxic conjugates of glutathione. These sensitive and comprehensive methods for organic contaminant discovery will subsequently be applied to unique environmental archives, including an ice core from Ellesmere Island and archived polar bear serum from two populations. Such new screening tools will revolutionize contaminant discovery by allowing unknown chemicals to be detected in environmental samples before they become widespread global threats. The new discoveries my HQP make through this research will lead to better domestic and international chemical management and a safer environment.

大多数有机污染物，包括那些在国际上被归类为“持久性有机污染物”（POPs）的污染物，都是经过几十年的密集使用才在环境中发现的。这种发现上的长期拖延是由于传统上依赖于有针对性的分析方法，而这种方法往往由于缺乏真正的化学标准而受到限制。通过我的NSERC发现研究项目，我将开发强大的筛选技术，以非靶向方式识别新的污染物。换句话说，我的目标是发现重要的污染物，而不需要事先知道它们的存在。提出了一种“发现暴露”工作流程，包括敏感的样品制备技术与一系列强大的仪器方法相结合，这些方法能够分离和识别可能具有生物累积性、持久性和毒性的痕量未知物质。将开发用于分离人类血液和尿液的疏水（生物蓄积性）和极性组分的大体积搅拌棒吸附萃取（SBSE）方法，并将使用氧化试验来识别最持久的未知化学物质。我们将验证三种分析方法来分析样品馏分，包括高效液相色谱法和高效超临界流体色谱法，以及在全扫描下操作的超高分辨率质谱法，以及设计用于检测卤化化学物质和谷胱甘肽有毒偶联物的独特标记模式。这些灵敏而全面的有机污染物发现方法随后将应用于独特的环境档案，包括来自埃尔斯米尔岛的冰芯和来自两个种群的北极熊血清档案。这种新的筛选工具将彻底改变污染物的发现，允许在环境样本中检测出未知的化学物质，以免它们成为广泛的全球威胁。通过这项研究，我的HQP有了新的发现，这将有助于改善国内外的化学品管理和更安全的环境。