title: Phthalic acid is the main metabolite of the plasticizer di(2-ethylhexyl) phthalate in peritoneal dialysis patients.
abstract: 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.
authors.affiliation: Division of Nephrology, Robert Bosch Hospital, Stuttgart, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Mettang
authors.forename: D M
authors.initials: DM
authors.lastname: Alscher
authors.forename: C
authors.initials: C
authors.lastname: Pauli-Magnus
authors.forename: R
authors.initials: R
authors.lastname: Dunst
authors.forename: U
authors.initials: U
authors.lastname: Kuhlmann
authors.forename: A W
authors.initials: AW
authors.lastname: Rettenmeier
mesh_terms: D002849:Chromatography, Gas; D004051:Diethylhexyl Phthalate / Q000097:blood / Q000378:metabolism* / Q000652:urine; D006801:Humans; D013058:Mass Spectrometry; D010531:Peritoneal Dialysis, Continuous Ambulatory; D010795:Phthalic Acids / Q000378:metabolism*; D010968:Plasticizers / Q000378:metabolism*; D014511:Uremia / Q000378:metabolism / Q000628:therapy
chemical_list: D010795:Phthalic Acids; D010968:Plasticizers; C032279:phthalic acid; D004051:Diethylhexyl Phthalate