The fate of leached di(2-ethylhexyl)phthalate in patients undergoing CAPD treatment

Abstract

Objectives: To evaluate the degree of exposure to and the fate of di(2-ethylhexyl)phthalate (DEHP) and its major derivatives mono(2-ethylhexyl)phthalate (MEHP), 2-ethylhexanol (2-EH), and phthalic acid (PA) in patients undergoing regular continuous ambulatory peritoneal dialysis (CAPD) during a 4-hour dwell period. Design: Prospective, controlled. Setting: Teaching hospital, Department of Nephrology. Participants: Seven elderly patients on stable CAPD using Fresenius instruments and dialysate and 6 age-matched healthy controls. Interventions: During a routinely performed peritoneal equilibration test (PET), blood and dialysate samples were drawn before and 120 and 240 min after the dwell was started. In addition, blood samples were taken from a group of volunteers participating in a pharmacological study. Measurements: Quantitative analysis of DEHP and its hydrolysis products was performed by selected ion-monitoring gas chromatography/mass spectrometry, operating the mass spectrometer in a combined positive and negative ion chemical ionization mode. Results: Serum concentrations of DEHP and PA were significantly higher in patients (median: 0.079 μg/mL, range: 0.032-0.210 μg/mL; and 0.167 μg/mL, range: 0.097-0.231 μg/mL, respectively) than in controls [0.0195 μg/mL, range: 0.016-0.025 μg/mL (p = 0.0027) and 0.0120 μg/mL, range: 0.006-0.034 μg/mL(p = 0.0026), respectively]. Concentration of MEHP in the fluid of CAPD bags prior to use was four times higher than that of the parent compound. During the first 4 hours of dwell time, the concentrations of MEHP and 2-EH in dialysate consistently decreased from 0.177 (range: 0.137-0.239 μg/ mL) to 0.022 μg/mL (range: 0.005-0.058 μg/mL) (p 0.017), and from 0.087 (range: 0.075-0.097 μg/mL) to 0.05 μg/mL (range: 0.023-0.064 μg/mL) (p = 0.017), respectively, while the concentration of DEHP remained stable. Remarkably high concentrations of PA (0.129 μg/mL; range: 0.038-0.466 μg/mL) were found in CAPD bags prior to use, and these concentrations tended to increase during dwell time, without statistical significance, however (0.135 μg/mL; range: 0.073-0.659 μg/mL, p = 0.062). Conclusions: Patients on CAPD are regularly exposed to considerable amounts of phthalic ester derivatives, mainly to MEHP and PA. MEHP seems to be well absorbed by the peritoneal membrane. The long-term effects of this exposure remain to be elucidated.