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

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”（POP）的污染物，都是经过几十年的大量使用才在环境中发现的。发现过程中的长期拖延是传统上依赖于有针对性的分析方法的结果，而这些方法往往受到缺乏真实化学标准的限制。通过我的NSERC发现研究计划，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，我的目标是在没有任何先前知识的情况下发现重要的污染物。提出了一种“发现化学组学”工作流程，其中包括灵敏的样品制备技术，再加上一套强大的仪器方法，能够分离和鉴定具有潜在生物累积性、持久性和毒性的痕量未知物质。将开发大体积搅拌棒吸附萃取法，用于分离人体血液和尿液中的疏水性（生物累积性）和极性部分，并将使用氧化试验来确定最持久的未知化学品。我们将验证三种分析方法来分析样品馏分，包括HPLC和高效超临界流体色谱法，该色谱法与全扫描操作的高分辨质谱法相连接，并具有独特的标记模式，旨在检测卤化化学品和谷胱甘肽的有毒结合物。这些敏感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，包括埃尔斯米尔岛的冰芯和两个种群的存档北极熊血清。这种新的筛选工具将彻底改变污染物的发现，使未知的化学物质在环境样本中被检测出来，然后才成为广泛的全球威胁。我的HQP通过这项研究取得的新发现将导致更好的国内和国际化学品管理和更安全的环境。

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.