Mettang T, Alscher D M, Pauli-Magnus C, Dunst R, Kuhlmann U, Rettenmeier A W
Division of Nephrology, Robert Bosch Hospital, Stuttgart, Germany.
Adv Perit Dial. 1999;15:229-33.
Di(2-ethylhexyl) phthalate (DEHP) is the most commonly used plasticizer in polyvinyl chloride (PVC) plastics, and is therefore a major constituent of continuous ambulatory peritoneal dialysis (CAPD) bags. Because DEHP is not chemically bound, it leaches out of the plastic matrix. Recently, we found that leukocyte function in vitro is impaired by a mixture of metabolites of DEHP. In the present study, we investigated the metabolism of DEHP in patients on CAPD. The study group consisted of 10 stable patients, on CAPD for at least 6 months, using a plasticizer-containing PVC PD system [ANDY Plus (Fresenius Medical Care, Bad Homburg, Germany)]. Effluent dialysate and urine samples were collected over 24 hours, and a 10 mL blood sample was drawn. Concentrations of DEHP and its metabolites mono(2-ethylhexyl) phthalate (MEHP), phthalic acid (PA), and 2-ethylhexanol (2-EH) were determined in urine, dialysate, and serum using gas chromatography/mass spectrometry. Additionally, the degree of glucuronidation of the phthalic acid esters in urine were determined. In serum, dialysate, and urine, PA was the predominant metabolite of DEHP (0.205 +/- 0.067 mg/L, 0.284 +/- 0.180 mg/L, and 1.34 +/- 1.00 mg/L, respectively), but concentrations of MEHP were low (0.0100 +/- 0.0056 mg/L, 0.022 +/- 0.008 mg/L, 0.011 +/- 0.0064 mg/L, respectively). Urinary MEHP was glucuronidated to approximately 15%. PA was 35% eliminated as a glucuronide. Unlike healthy subjects, PD patients do not eliminate DEHP mainly in the form of MEHP or MEHP metabolites. They further break these compounds down to PA. The fact that concentrations of PA in urine exceed by far the respective serum concentrations indicates that PA is secreted by the kidney. Further research on the toxicological aspects of plasticizers in uremic patients should take these findings into account.
邻苯二甲酸二（2-乙基己基）酯（DEHP）是聚氯乙烯（PVC）塑料中最常用的增塑剂，因此是持续性非卧床腹膜透析（CAPD）袋的主要成分。由于DEHP并非化学键合在塑料中，它会从塑料基质中渗出。最近，我们发现DEHP的代谢产物混合物会损害体外白细胞功能。在本研究中，我们调查了CAPD患者体内DEHP的代谢情况。研究组由10名稳定的患者组成，他们使用含增塑剂的PVC腹膜透析系统[安迪加（费森尤斯医疗，德国巴特洪堡）]进行CAPD治疗至少6个月。在24小时内收集流出的透析液和尿液样本，并采集10 mL血样。使用气相色谱/质谱法测定尿液、透析液和血清中DEHP及其代谢产物单（2-乙基己基）邻苯二甲酸酯（MEHP）、邻苯二甲酸（PA）和2-乙基己醇（2-EH）的浓度。此外，还测定了尿液中邻苯二甲酸酯的葡萄糖醛酸化程度。在血清、透析液和尿液中，PA是DEHP的主要代谢产物（分别为0.205±0.067 mg/L、0.284±0.180 mg/L和1.34±1.00 mg/L），但MEHP的浓度较低（分别为0.0100±0.0056 mg/L、0.022±0.008 mg/L、0.011±0.0064 mg/L）。尿液中的MEHP约15%葡萄糖醛酸化。PA以葡萄糖醛酸酯形式消除的比例为35%。与健康受试者不同，腹膜透析患者并非主要以MEHP或MEHP代谢产物的形式消除DEHP。他们会将这些化合物进一步分解为PA。尿液中PA的浓度远远超过相应血清浓度这一事实表明PA是由肾脏分泌的。对尿毒症患者增塑剂毒理学方面的进一步研究应考虑到这些发现。
