Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 704, Taiwan.
Institute of Biomedical Chemistry, 119121 Moscow, Russia.
J Food Drug Anal. 2019 Apr;27(2):585-594. doi: 10.1016/j.jfda.2018.11.002. Epub 2018 Dec 11.
Di-(2-propylheptyl) phthalate (DPHP) is a plasticizer and has been suggested to be a subchronic toxicant in rats. DPHP has been approved to be used in food containers and handling by the U.S. Food and Drug Administration. The use of DPHP is still increasing, and the risk of human exposure to DPHP via food may be high. Exposure markers measured in human samples are commonly used to monitor human exposure levels. Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and a rat model were used to discover tentative DPHP exposure markers. DPHP and mono-(2-propylheptyl) phthalate (MPHP) were used as the precursors for calculating metabolite candidates using biotransformation mass changes of known enzymatic reactions. A rat model was designed to validate these metabolite candidates as tentative exposure markers. A total of 28 signals show dose-response relationships and these signals contain a few isomers. The chemical structures of 15 tentative exposure marker signals were speculated based on the product ion mass spectra from MS/MS analysis. These 15 signals included 7 chemical structures and some of them may be isomers. The different arrangement of the atoms in space of these isomers should be validated by standard compounds in the future studies. Among the 7 speculated chemical structures, 2 structures were novel tentative DPHP metabolites, and 5 structures have been previously reported in the literature. The results indicate that using UPLC-MS and a rat model can be used to identify tentative toxicant exposure markers.
邻苯二甲酸二（2-丙基庚基）酯（DPHP）是一种增塑剂，据报道它对大鼠具有亚慢性毒性。美国食品药品监督管理局已批准 DPHP 用于食品容器和处理。DPHP 的使用仍在增加，人类通过食物接触 DPHP 的风险可能很高。人体样本中测量的暴露标志物通常用于监测人体的暴露水平。超高效液相色谱-质谱（UPLC-MS）和大鼠模型被用于发现暂定的 DPHP 暴露标志物。DPHP 和单（2-丙基庚基）邻苯二甲酸酯（MPHP）被用作前体，通过已知酶促反应的生物转化质量变化来计算代谢物候选物。设计了大鼠模型来验证这些代谢物候选物作为暂定暴露标志物。共有 28 个信号显示出剂量反应关系，这些信号包含一些异构体。基于 MS/MS 分析的产物离子质谱，推测了 15 个暂定暴露标志物信号的化学结构。这些信号包含 7 种化学结构，其中一些可能是异构体。这些异构体在空间中原子的不同排列应在未来的研究中通过标准化合物进行验证。在这 7 种推测的化学结构中，有 2 种结构是新的暂定 DPHP 代谢物，5 种结构以前在文献中报道过。结果表明，使用 UPLC-MS 和大鼠模型可以用于鉴定暂定的有毒物暴露标志物。
