Circulating concentrations of di(2-ethylhexyl) phthalate and its de-esterified phthalic acid products following plasticizer exposure in patients receiving hemodialysis

Abstract

The degree of exposure to the plasticizer di(2-ethylhexyl) phthalate (DEHP) was assessed in 11 patients undergoing maintenance hemodialysis for the treatment of renal failure. The amount of DEHP leached from the dialyzer during a 4-hr dialysis session was estimated by monitoring the DEHP blood concentration gradient across the dialyzer. Circulating concentrations of the biologically active products of DEHP de-esterification, viz., mono(2-ethylhexyl) phthalate (MEHP) and phthalic acid, were also determined during the dialysis session. On the average, an estimated 105 mg of DEHP was extracted from the dialyzer during a single dialysis session, with a range of 23.8 to 360 mg. The rate of extraction of DEHP from the dialyzer was correlated with serum lipid content as expressed by the sum of serum cholesterol and triglyceride concentrations (r = +0.65, p less than 0.05). Time-averaged circulating concentrations of MEHP during dialysis (1.33 +/- 0.58 micrograms/ml) were similar to those of DEHP (1.91 +/- 2.11 micrograms/ml). Blood concentrations of phthalic acid (5.22 +/- 3.94 micrograms/ml) were higher than those of the esters. The length of time patients had been receiving regular dialysis treatment was not a determinant of circulating concentrations of DEHP or MEHP. In contrast, time-averaged circulating concentrations of phthalic acid correlated strongly with the duration (in years) of dialysis treatment (r = +0.92, p less than 0.001). The results indicated substantial exposure to DEHP during hemodialysis and that the de-esterified products of DEHP are present in significant concentrations in the systemic circulation. Further study is needed to assess the contribution of these metabolites to the biological actions of DEHP in man.