Nomasa Karin, Oya Naoko, Ito Yuki, Terajima Takehito, Nishino Takahiro, Mohanto Nayan Chandra, Sato Hirotaka, Tomizawa Motohiro, Kamijima Michihiro
Department of Occupational and Environmental Health, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Research Fellow of Japan Society for the Promotion of Science, Tokyo, Japan.
J Occup Health. 2021 Jan;63(1):e12218. doi: 10.1002/1348-9585.12218.
The comprehensive detection of environmental chemicals in biospecimens, an indispensable task in exposome research, is advancing. This study aimed to develop an exposomic approach to identify urinary metabolites of organophosphate (OP) pesticides, specifically cadusafos and prothiofos metabolites, as an example chemical group, using an original metabolome dataset generated from animal experiments.
Urine samples from 73 university students were analyzed using liquid chromatography-high-resolution mass spectrometry. The metabolome data, including the exact masses, retention time (t ), and tandem mass spectra obtained from the human samples, were compared with the existing reference databases and with our original metabolome dataset for cadusafos and prothiofos, which was produced from mice to whom two doses of these OPs were orally administered.
Using the existing databases, one chromatographic peak was annotated as 2,4-dichlorophenol, which could be a prothiofos metabolite. Using our original dataset, one peak was annotated as a putative cadusafos metabolite and three peaks as putative prothiofos metabolites. Of these, all three peaks suggestive of prothiofos metabolites, 2,4-dichlorophenol, 3,4,5-trihydroxy-6-(2,4-dichlorophenoxy) oxane-2-carboxylic acid, and (2,4-dichlorophenyl) hydrogen sulfate were confirmed as authentic compounds by comparing their peak data with both the original dataset and peak data of the standard reagents. The putative cadusafos metabolite was identified as a level C compound (metabolite candidate with limited plausibility).
Our developed method successfully identified prothiofos metabolites that are usually not a target of biomonitoring studies. Our approach is extensively applicable to various environmental contaminants beyond OP pesticides.
生物样本中环境化学物质的综合检测是暴露组研究中一项不可或缺的任务，目前正在不断推进。本研究旨在开发一种暴露组学方法，以动物实验产生的原始代谢组数据集为例，鉴定有机磷（OP）农药的尿代谢物，特别是硫线磷和丙硫磷的代谢物。
使用液相色谱-高分辨率质谱法分析73名大学生的尿液样本。将从人类样本中获得的代谢组数据，包括精确质量、保留时间（t）和串联质谱，与现有的参考数据库以及我们针对硫线磷和丙硫磷的原始代谢组数据集进行比较，该数据集是由口服这两种OP的小鼠产生的。
使用现有的数据库，一个色谱峰被注释为2,4-二氯苯酚，它可能是丙硫磷的代谢物。使用我们的原始数据集，一个峰被注释为推定的硫线磷代谢物，三个峰被注释为推定的丙硫磷代谢物。其中，通过将它们的峰数据与原始数据集和标准试剂的峰数据进行比较，所有三个提示丙硫磷代谢物的峰，即2,4-二氯苯酚、3,4,5-三羟基-6-(2,4-二氯苯氧基)氧杂环丁烷-2-羧酸和(2,4-二氯苯基)硫酸氢盐被确认为真实化合物。推定的硫线磷代谢物被鉴定为C级化合物（可信度有限的代谢物候选物）。
我们开发的方法成功鉴定了通常不是生物监测研究目标的丙硫磷代谢物。我们的方法广泛适用于除OP农药之外的各种环境污染物。
