Koo Hyun Jung, Lee Byung Mu
Division of Toxicology, College of Pharmacy, Sungkyunkwan University, Suwon, Kyonggi-do, South Korea.
J Toxicol Environ Health A. 2007 Mar 1;70(5):383-7. doi: 10.1080/15287390600882150.
The toxicokinetic relationship between di(2-ethylhexyl) phthalate (DEHP) and mono(2-ethylhexyl) phthalate (MEHP), a major metabolite of DEHP, was investigated in Sprague-Dawley rats orally treated with a single dose of 14C-DEHP. Urinary excretion of total 14C-DEHP and of its metabolites was followed by liquid scintillation counting (LSC). Concentrations of DEHP and MEHP were determined 6, 24, and 48 h after treatment in rat serum and 6, 12, 24, and 48 h after treatment in urine by high-performance liquid chromatography (HPLC). After 24 h, peak concentrations of MEHP in both urine and serum were observed in animals treated with 40, 200, or 1000 mg DEHP/kg. HPLC showed that general toxicokinetic parameters, such as Tmax (h), Cmax (microg/ml), Ke (1/h), and AUC (microg-h/ml/) were greater for MEHP than DEHP in both urine and serum. In contrast, the half-lives (t1/2 [h]) of DEHP were greater than those of MEHP. The AUC ratios between DEHP and MEHP were relatively smaller in serum than in urine, suggesting the important role of urinary DEHP data for exposure assessment of DEHP. The toxicokinetic relationship between DEHP and MEHP in rats suggests that DEHP exposure assessment should be based on DEHP and MEHP in urine and serum for risk assessment applications.
在经单剂量14C-邻苯二甲酸二（2-乙基己基）酯（DEHP）口服处理的Sprague-Dawley大鼠中，研究了DEHP与其主要代谢物单（2-乙基己基）邻苯二甲酸酯（MEHP）之间的毒代动力学关系。通过液体闪烁计数（LSC）追踪总14C-DEHP及其代谢物的尿排泄情况。采用高效液相色谱法（HPLC）测定处理后6、24和48小时大鼠血清中DEHP和MEHP的浓度，以及处理后6、12、24和48小时尿液中DEHP和MEHP的浓度。24小时后，在接受40、200或1000 mg DEHP/kg处理的动物的尿液和血清中均观察到MEHP的峰值浓度。HPLC显示，尿液和血清中MEHP的一般毒代动力学参数，如达峰时间（Tmax，小时）、峰浓度（Cmax，微克/毫升）、消除速率常数（Ke，1/小时）和曲线下面积（AUC，微克-小时/毫升）均高于DEHP。相比之下，DEHP的半衰期（t1/2，小时）大于MEHP。血清中DEHP与MEHP的AUC比值相对小于尿液中的比值，这表明尿液中DEHP数据在DEHP暴露评估中具有重要作用。大鼠中DEHP与MEHP之间的毒代动力学关系表明，在风险评估应用中，DEHP暴露评估应基于尿液和血清中的DEHP和MEHP。
