First insights in the metabolism of phosphate flame retardants and plasticizers using human liver fractions
First insights in the metabolism of phosphate flame retardants and plasticizers using human liver fractions
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DOI：
10.1016/j.toxlet.2013.08.012
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发表时间：
2013-10-23
影响因子：
3.5
通讯作者：
Covaci, Adrian
中科院分区：
文献类型：
--
作者：
Van den Eede, Nele;Maho, Walid;Covaci, Adrian
磷酸盐阻燃剂和增塑剂（PFR）是广泛用于聚合物的添加剂。重要的代表性化合物如磷酸三（2-丁氧基乙基）酯（TBOEP）、磷酸三苯酯（TPHP）、磷酸三（2-氯乙基）酯（TCEP）、磷酸三（1-氯-2-丙基）酯（TCIPP）、磷酸三（1，3-二氯-2-丙基）酯（TDCIPP）等在室内环境中已发现高浓度存在。需要研究这些PFR的生物转化，因为它可能是其在人体内生物利用度和毒性的主要决定因素。将TBOEP、TPHP、TCEP、TCIPP和TDCIPP与人肝S9组分和微粒体孵育。使用与四极杆飞行时间质谱仪偶联的液相色谱法分析上清液。扫描色谱图以确定是否存在I相和II相代谢物，并根据分子式、同位素模式和MS/MS光谱的质量准确度进行初步鉴别。TBOEP的两个主要代谢产物分别是O-脱烷基化和羟基化产物。TPHP主要通过O-脱芳基作用转化为双酯代谢产物和羟基化代谢产物。TCEP很少代谢成其二酯和氧化脱卤产物。TCIPP的主要代谢产物为氧化脱卤产物。TDCIPP主要转化为二酯和谷胱甘肽S-结合物。本研究中确定的代谢物是未来人体生物监测研究的候选生物标志物。(C)2013爱思唯尔爱尔兰有限公司版权所有。
Phosphate flame retardants and plasticizers (PFRs) are additives used in a wide range of polymers. Important representatives, such as tris(2-butoxyethyl) phosphate (TBOEP), triphenyl phosphate (TPHP), tris(2-chloroethyl) phosphate (TCEP), tris(1-chloro-2-propyl) phosphate (TCIPP), tris(1,3-dichloro-2propyl) phosphate (TDCIPP), have been found in the indoor environment at high levels. Biotransformation of these PFRs needs to be investigated because it can be a major determinant of their bioavailability and toxicity in humans. TBOEP, TPHP, TCEP, TCIPP and TDCIPP were incubated with human liver S9 fraction and microsomes. Supernatants were analyzed using a liquid chromatography coupled to a quadrupoletime-of-flight mass spectrometer. Chromatograms were scanned for the presence of Phase-I and Phase-II metabolites and tentatively identified based on mass accuracy of the molecular formula, isotopic pattern, and MS/MS spectra. The two major metabolites of TBOEP were products of O-dealkylation and of hydroxylation, respectively. TPHP was mainly transformed to its diester metabolite by O-dearylation and to a hydroxylated metabolite. TCEP was poorly metabolized into its diester and a product of oxidative dehalogenation. The major metabolite of TCIPP was a product of oxidative dehalogenation. TDCIPP was mainly transformed into its diester and a glutathione S-conjugate. The metabolites identified in the present study are candidate biomarkers for future human biomonitoring studies. (C) 2013 Elsevier Ireland Ltd. All rights reserved.