Di(2-ethylhexyl)phthalate (DEHP) metabolites in human urine and serum after a single oral dose of deuterium-labelled DEHP
Di(2-ethylhexyl)phthalate (DEHP) metabolites in human urine and serum after a single oral dose of deuterium-labelled DEHP
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DOI：
10.1007/s00204-003-0522-3
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发表时间：
2004-03
影响因子：
6.1
通讯作者：
H. Koch;H. Bolt;J. Angerer
中科院分区：
文献类型：
--
作者：
H. Koch;H. Bolt;J. Angerer
研究了一名男性志愿者单次口服48.1 mg邻苯二甲酸二（2-乙基己基）酯（DEHP）后的人体代谢。为了避免背景暴露的干扰，给药了D4环标记的DEHP类似物。在尿液和血清中分别监测44 h和8 h三种代谢产物邻苯二甲酸单（2-乙基-5-羟己基）酯（5 OH-MEHP）、邻苯二甲酸单（2-乙基-5-氧代己基）酯（5 oxo-MEHP）和邻苯二甲酸单（2-乙基己基）酯（MEHP）的排泄。2 h后在血清中以及2 h后（MEHP）和4 h后（5 OH-MEHP和5 oxo-MEHP）在尿液中发现所有代谢物的峰浓度。血清中的主要代谢产物为MEHP，尿液中的主要代谢产物为5 OH-MEHP，其次为5 oxo-MEHP和MEHP。尿液排泄遵循多相消除模型。经过4 - 8 h的吸收和分布相后，第一消除相的排泄半衰期约为2 h，5 OH-和5 oxo-MEHP的半衰期略长。第二阶段（给药后14至18小时开始）的半衰期为MEHP 5小时，5 OH-MEHP和5 oxo-MEHP为10小时。在36 - 44 h的时间窗内，未观察到5 OH-和5 oxo-MEHP的排泄浓度降低。在第一消除相（给药后8 - 14 h），MEHP与5 oxo-MEHP和MEHP与5 OH-MEHP的平均排泄比分别为1：1.8和1：3.1。在给药后24小时内的第二消除相，MEHP与5-oxo-MEHP与5-OH-MEHP的平均排泄比为1：5.0：9.3。5 OH-MEHP与5 oxo-MEHP的排泄比随时间推移保持恒定，平均值为1.7。44小时后，47%的DEHP剂量经尿液排泄，包括MEHP（7.3%）、5 OH-MEHP（24.7%）和5 oxo-MEHP（14.9%）。
Human metabolism of di(2-ethylhexyl)phthalate (DEHP) was studied after a single oral dose of 48.1 mg to a male volunteer. To avoid interference by background exposure the D4-ring-labelled DEHP analogue was dosed. Excretion of three metabolites, mono(2-ethyl-5-hydroxyhexyl)phthalate (5OH-MEHP), mono(2-ethyl-5-oxohexyl)phthalate (5oxo-MEHP) and mono(2-ethylhexyl)phthalate (MEHP), was monitored for 44 h in urine and for 8 h in serum. Peak concentrations of all metabolites were found in serum after 2 h and in urine after 2 h (MEHP) and after 4 h (5OH-MEHP and 5oxo-MEHP). While the major metabolite in serum was MEHP, the major metabolite in urine was 5OH-MEHP, followed by 5oxo-MEHP and MEHP. Excretion in urine followed a multi-phase elimination model. After an absorption and distribution phase of 4 to 8 h, half-life times of excretion in the first elimination phase were approximately 2 h with slightly higher half-life times for 5OH- and 5oxo-MEHP. Half-life times in the second phase—beginning 14 to 18 h post dose—were 5 h for MEHP and 10 h for 5OH-MEHP and 5oxo-MEHP. In the time window 36 to 44 h, no decrease in excreted concentrations of 5OH- and 5oxo-MEHP was observed. In the first elimination phase (8 to 14 h post dose), mean excretion ratios of MEHP to 5oxo-MEHP and MEHP to 5OH-MEHP were 1 to 1.8 and 1 to 3.1. In the second elimination phase up to 24 h post dose mean excretion ratios of MEHP to 5oxo-MEHP to 5OH-MEHP were 1 to 5.0 to 9.3. The excretion ratio of 5OH-MEHP to 5oxo-MEHP remained constant through time at 1.7 in the mean. After 44 h, 47% of the DEHP dose was excreted in urine, comprising MEHP (7.3%), 5OH-MEHP (24.7%) and 5oxo-MEHP (14.9%).