Distribution of di(2-ethylhexyl) phthalate and products in blood and blood components.

Abstract

In order to impart flexibility, plastic medical devices incorporate liquid plasticizers into their structure. Data from several laboratories, including ours, have shown that these compounds leach from blood bags and tubing during collection of blood, storage of various blood components and during kidney dialysis and cell and plasma apheresis procedures. After the plasticizer di(2-ethylhexyl) phthalate leaches from poly(vinyl chloride) blood packs, it is converted by a plasma enzyme to a more toxic metabolite, mono(2-ethylhexyl) phthalate. Blood fractionation products from outdated plasma contain mono(2-ethylhexyl) phthalate, the highest level being found in normal serum albumin. Recently, we have reported that di(2-ethylhexyl) phthalate actually binds to the red blood cell membrane and reduces its osmotic fragility. Current methods of red cells storage, which permit utilization up to 35 days after collection, are not possible without this membrane stabilization. Platelets are now stored for 5 days in the Fenwal PL 732 polyolefin bag. Although stated to be essentially free of liquid plasticizers, a significant level of leaching from this bag into the extracts of stored platelet concentrates was observed.

The Blood Bag Plasticizer Di-2-Ethylhexylphthalate Causes Red Blood Cells to Form Stomatocytes, Possibly by Inducing Lipid Flip-Flop

“…The ratio of DEHP to lipids in stored RBCs is calculated first based on literature values for the lipid content of RBCs [27] and for the amount of DEHP associated with the RBC membrane, which has been measured for RBCs stored as RCCs using radiolabeled DEHP [3]. Lipids can be extracted from RBCs with a yield of 3.15 μmol cholesterol and 3.90 μmol phospholipid per milliliter of packed cells [27], for a total lipid content of approximately 4.3 mg/ml, if we assume an approximate molecular weight of 800 Da for the phospholipids.…”

“…Lipids can be extracted from RBCs with a yield of 3.15 μmol cholesterol and 3.90 μmol phospholipid per milliliter of packed cells [27], for a total lipid content of approximately 4.3 mg/ml, if we assume an approximate molecular weight of 800 Da for the phospholipids. The DEHP associated with the membrane at day 28 of the RCC storage is 11.6% of the 80 μg/ml of DEHP that is extracted from the blood bag [3], or 9.3 μg DEHP/ml. …”

“…The DEHP is known to have a beneficial effect on RBCs that are stored for transfusion, reducing susceptibility to hemolysis [8,9,10,29] and minimizing the formation of both echinocytes [10] and microparticles [8,9,10,11]. Hemolysis, vesicle formation, and the shape changes associated with echinocyte formation are associated with the membrane; together with the known association of DEHP with the RBC membrane [3], this makes the DEHP-membrane interactions a specific target to study. The focus of the work presented here is on the link between DEHP and RBC shape, a feature that is readily observable and that can be used to track both the interactions of added molecules with RBCs and the transverse movement of such molecules between the two leaflets of the lipid bilayer [14,20].…”

“…During standard storage procedures, this addition happens when the DEHP leaches slowly out of the bags during the period when the plastic is in contact with plasma [2,3]. Introduction of DEHP to cell suspensions has been accomplished previously with the help of an emulsifier [10] and by addition of DEHP to plasma [8], but both the emulsifier [10] and the albumin found in plasma [22,23] affect the RBC shape.…”

“…This DEHP is not extracted from the bag by aqueous solutions of salts, but by solutions that contain albumin [2]. Red cell concentrates (RCCs) that are stored for transfusions do contain albumin, and can extract DEHP from the bag; by day 28 of the storage period, the total DEHP concentration for RCCs stored in PVC/DEHP blood bags has been measured at 80 μg/ml [3]. …”