Di(2-ethylhexyl) adipate (DEHA) is used as a substitute for the reprotoxic phthalate plasticizer di(2-ethylhexyl) phthalate (DEHP). This study reports the first quantitative data on human in vivo DEHA metabolism and urinary metabolite excretion with the aim of providing tools for DEHA exposure and risk assessments. After DEHA was administered to four healthy volunteers (107-164 µg/kg body weight (bw)), urine samples were continuously and completely collected for 48 h and analyzed for the specific oxidized monoester metabolites mono-2-ethyl-5-hydroxyhexyl adipate (5OH-MEHA), mono-2-ethyl-5-oxohexyl adipate (5oxo-MEHA), and mono-5-carboxy-2-ethylpentyl adipate (5cx-MEPA), as well as for the non-specific hydrolysis product adipic acid (AA) using stable isotope dilution analysis. AA was confirmed as a major (urinary excretion fraction (FUE): 10-40%), yet non-specific DEHA metabolite. 5cx-MEPA was the major specific DEHA metabolite with an FUE of 0.20% (range: 0.17-0.24%). FUEs for 5OH-MEHA and 5oxo-MEHA were 0.07% (0.03-0.10%) and 0.05% (0.01-0.06%), respectively. The three specific metabolites were excreted with two concentration maxima (tmax1 = 1.5-2.3 h, tmax2 = 3.8-6.4 h). Elimination half-lives (t1/2, calculated after the second tmax) for 5cx-MEPA were calculated between 2.1 to 3.8 h. The majority (98-100%) of metabolites was excreted within 24 hours. The FUE of 5cx-MEPA was applied to demonstrate its applicability for calculating daily intakes based on urinary metabolite levels from three pilot populations. Daily intakes were generally far below the tolerable daily intake (TDI) for DEHA (300 µg/kg bw/day). The highest daily intake (114 µg/kg bw/day) was calculated in individuals after consuming food that had been wrapped in DEHA containing cling film.

中文翻译：

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单次口服后四名志愿者的己二酸二（2-乙基己基）酯 (DEHA) 的代谢和尿排泄动力学

己二酸二（2-乙基己基）酯（DEHA）用作对生殖毒性邻苯二甲酸酯增塑剂邻苯二甲酸二（2-乙基己基）酯（DEHP）的替代品。本研究报告了人类体内 DEHA 代谢和尿代谢物排泄的第一个定量数据，旨在为 DEHA 暴露和风险评估提供工具。对四名健康志愿者 (107-164 µg/kg 体重 (bw)) 施用 DEHA 后，连续完整收集尿样 48 小时，并分析特定氧化单酯代谢物己二酸单-2-乙基-5-羟基己酯(5OH-MEHA)、己二酸单-2-乙基-5-氧己酯 (5oxo-MEHA) 和己二酸单-5-羧基-2-乙基戊酯 (5cx-MEPA)，以及非特异性水解产物己二酸酸 (AA) 使用稳定同位素稀释分析。AA被确认为主要（尿排泄分数（FUE）：10-40％），非特异性 DEHA 代谢物。5cx-MEPA 是主要的特定 DEHA 代谢物，FUE 为 0.20%（范围：0.17-0.24%）。5OH-MEHA 和 5oxo-MEHA 的 FUE 分别为 0.07% (0.03-0.10%) 和 0.05% (0.01-0.06%)。三种特定代谢物以两个浓度最大值（tmax1 = 1.5-2.3 h，tmax2 = 3.8-6.4 h）排出体外。5cx-MEPA 的消除半衰期（t1/2，在第二个 tmax 之后计算）计算在 2.1 到 3.8 小时之间。大多数 (98-100%) 代谢物在 24 小时内排出体外。应用 5cx-MEPA 的 FUE 来证明其基于三个试点人群的尿代谢物水平计算每日摄入量的适用性。每日摄入量通常远低于 DEHA 的每日可耐受摄入量 (TDI)（300 微克/千克体重/天）。