New Analytical Framework for Verification of Biomarkers of Exposure to Chemicals Combining Human Biomonitoring and Water Fingerprinting
New Analytical Framework for Verification of Biomarkers of Exposure to Chemicals Combining Human Biomonitoring and Water Fingerprinting
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DOI：
10.1021/acs.analchem.7b01527
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发表时间：
2017-07-04
影响因子：
7.4
通讯作者：
Kasprzyk-Hordern, Barbara
中科院分区：
文献类型：
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作者：
Lopardo, Luigi;Cummins, Andrew;Kasprzyk-Hordern, Barbara
人体生物监测中的分子流行病学方法是验证公众接触化学物质的有力工具。不幸的是，由于后勤困难和高成本，它们往往评估小型研究小组，因此可能无法提供全面的大规模全社区接触数据。城市水指纹为传统方法提供了及时的替代方案。它可以彻底改变人类暴露研究，因为城市水代表了整个社区的集体暴露。了解暴露于特定化学物质的特征生物标志物是水指纹成功应用的关键。本研究旨在介绍一种新的概念分析框架，通过结合人体代谢和城市水指纹分析来鉴定公共暴露于化学物质的生物标志物。该框架包括以下步骤：(1)体外HLM/S9测定，(2)体内池尿测定，(3)体内废水指纹测定，(4)HR-MSMS分析，(5)数据处理，(6)生物标志物的选择。将该框架应用于PCMC（4-氯间甲酚），并对其进行了验证，PCMC（4-氯间甲酚）是一种家用衍生的抗菌药物，没有已知的暴露和人体代谢数据：使用体外HLM/S9法鉴定出PCMC的新代谢物（羟基化，硫酸化/羟基化，硫酸化PCMC和葡萄糖醛酸化PCMC）。但在废水和尿液中只发现了一种代谢物，硫酸化PCMC。因此，我们的研究证实了水指纹是一种很有前途的生物标志物选择工具，单独的体外HLM/S9研究虽然提供了信息，但不能提供高准确性的结果。我们的工作也首次证实了人体内对PCMC的暴露。
Molecular epidemiology approaches in human biomonitoring are powerful tools that allow for verification of public exposure to chemical substances. Unfortunately, due to logistical difficulties and high cost, they tend to evaluate small study groups and as a result might not provide comprehensive large scale community-wide exposure data. Urban water fingerprinting provides a timely alternative to traditional approaches. It can revolutionize the human exposure studies as urban water represents collective community-wide exposure. Knowledge of characteristic biomarkers of exposure to specific chemicals is key to the successful application of water fingerprinting. This study aims to introduce a novel conceptual analytical framework for identification of biomarkers of public exposure to chemicals via combined human metabolism and urban water fingerprinting assay. This framework consists of the following steps: (1) in vitro HLM/S9 assay, (2) in vivo pooled urine assay, (3) in vivo wastewater fingerprinting assay, (4) analysis with HR-MSMS, (5) data processing, and (6) selection of biomarkers. The framework was applied and validated for PCMC (4-chloro-m-cresol), household derived antimicrobial agent with no known exposure and human metabolism data: pour new metabolites of PCMC (hydroxylated, sulfated/hydroxylated, sulfated PCMC, and glucuronidated PCMC) were identified using the in vitro HLM/S9 assay. But only one metabolite, sulfated PCMC, was confirmed in wastewater and in urine. Therefore, our study confirms that water fingerprinting is a promising tool for biomarker selection and that in vitro HLM/S9 studies alone, although informative, do not provide high accuracy results. Our work also confirms, for the first time, human internal exposure to PCMC.