Contamination of Commercial Blood Products by Di-2-Ethylhexyl Phthalate and Mono-2-Ethylhexyl Phthalate

Abstract

Blood fractionation products obtained from three different manufacturers were analyzed to determine if either mono-2-ethylhexyl phthalate (MEHP) or di-2-ethylhexyl phthalate (DEHP) were contaminants of any of the fractionated proteins. The only protein fraction to contain DEHP was factor IX (23μg/ml) from one company. However, MEHP was detected in low levels in several of the 5% normal serum albumin, 5% plasma protein fraction, factor VIII and factor IX samples. 25% normal serum albumin contained the highest level of MEHP with concentrations of up to 300pg/ml (40% of the plasma level) depending on the sample. Attempts to remove MEHP using dialysis or ultrafiltration were unsuccessful and indicated a close association of the MEHP with albumin. There was a definite correlation between storage and transportation conditions and the level of MEHP in both plasma and 25% normal serum albumin. The highest levels of this phthalate acid ester were found in the products made from the plasma which had been shipped at ambient temperature. Contrary to published data, storage of plasma at -30°C for up to 6 months prevented the accumulation of MEHP.

Distribution of Di(2-Ethylhexyl) Phthalate and Products in Blood and Blood Components

“…Each cryoprecipitate contains approximately 20 ,ug/mL of DEHP (17). The higher purity VIIIC concentrates contain no DEHP and < 1 ,ug/mL MEHP (9). In a study carried out at the Ottawa Centre, DEHP blood levels were measured before and after infusion with cryoprecipitate into hemophiliac patients, and all of the DEHP was cleared from the blood 10 min after infusion.…”

“…Subsequent work has demonstrated *Ottawa Centre, Canadian Red Cross, Blood Transfusion Service, 85 Plymouth Street, Ottawa, Ontario, Canada KlS 3E2. tDepartment of Medicine, University of Ottawa, Ottawa, Ontario, Canada. that DEHP accumulates in stored whole blood, in platelet concentrates (PC) (3), in cryoprecipitates (8), and in plasma derivatives (9) where there is a particular association with albumin. An earlier publication had indicated that platelets were responsible for the leaching and subsequent plasma accumulation of DEHP However, work in our laboratory demonstrated that a plasma protein which is not associated with platelets is responsible for the accumulation of DEHP, and that the DEHP is, for the most part, bound to plasma proteins (6).…”

“…The accumulation of MEHP was shown to be a direct result of the hydrolysis of DEHP by a plasma enzyme (6). This enzyme cofractionates with albumin, and some commercial preparations of normal serum albumin (NSA) contain significant amounts of both DEHP and MEHP (9). MEHP accumulation is of concern because MEHP has been shown to be 20 times more toxic than DEHP in rats (10).…”

Plasticizer concentration in cord blood cryopreserved with DMSO

“…The conversion has been shown to increase with increasing storage time and temperature, while storage at low temperatures prevent it (Cole et al 1981, Inoue 2005, Rock et al 1978. MEHP has been measured in stored blood, blood products and peritoneal dialysate (Cole et al 1981, Labow et al 1986, Peck et al 1979, Rock et al 1978, Sjoberg et al 1985a, Sjoberg et al 1985b). Nevertheless, the data available are not sufficient to accurately calculate the in vitro conversion rates (Health Canada 2002).…”

Response to ‘Dr Raymond David, BASF Corporation’

“…The conversion has been shown to increase with increasing storage time and temperature, while storage at low temperatures prevent it (Cole et al 1981, Rock et al 1978. MEHP has been measured in stored blood, blood products and peritoneal dialysate (Cole et al 1981, Labow et al 1986, Peck et al 1979, Rock et al 1978, Sjoberg et al 1985a, Sjoberg et al 1985b). Nevertheless, the data available are not sufficient to accurately calculate the in vitro conversion rates (Health Canada 2002).…”