Perioperative exposure to plasticizers in patients undergoing cardiopulmonary bypass.

Di(2-ethylhexyl)phthalate and its principal metabolite, mono(2-ethylhexyl)phthalate, are contaminants of blood that are extracted on contact with polyvinylchloride surfaces, such as blood collection bags and tubing used in cardiopulmonary bypass. In this study, levels of the two plasticizers were measured in patients who underwent coronary artery bypass grafting, orthotopic transplantation, implantation of the Jarvik 7-70 total artificial heart during bridge-to-transplant procedures, and in infants who underwent corrective operations for congenital defects. In all adult patients the levels of di(2-ethylhexyl)phthalate increased tenfold by the end of cardiopulmonary bypass, whereas the levels of mono(2-ethylhexyl)phthalate increased ninefold. In infants, levels of di(2-ethylhexyl)phthalate rose seven times by the end of bypass and mono(2-ethylhexyl)phthalate rose significantly as well. In most of the patients having coronary bypass, the two plasticizers declined to preoperative levels within 24 hours. However, in some of the patients having orthotopic transplantation and in those in whom the Jarvik 7-70 total artificial heart was used as a bridge to transplant, the levels were still detectable 120 hours postoperatively. Circulating levels of mono(2-ethylhexyl)phthalate are only 20- to 35-fold lower in patients undergoing cardiac operations than the level of mono(2-ethylhexyl)phthalate causing a 50% reduction in developed contractile force and arrhythmias in an in vitro human atrial trabecular preparation. This study shows that patients with multisystem failure and infants may be at risk for this acute exposure to mono(2-ethylhexyl)phthalate.

Levels of plasticizer in the frequent plasma donor.

Di-2-ethylhexyl phthalate (DEHP), a commonly employed plasticizer reported to be carcinogenic in rats and mice, has been confirmed to leach from all plastic component parts of the equipment employed in plasma donation. Resident aqueous solutions of both sodium chloride and sodium citrate were found to contain only trace levels of DEHP (0.03 ppm), while stored plasma samples contained levels at least one order of magnitude higher (0.4 ppm). Since at least 5% of all plasma donations in the Los Angeles area are deemed to be of the high frequency classification, investigation into repeated red blood cell exposure to DEHP was considered imperative. However, there was no difference in the levels of DEHP found in the plasma of the frequent plasma donor (50-60 times per annum) relative to the first-time donor. It is concluded that there is no increased contamination threat to frequent plasma donation from migrating plasticizer via red blood cell exposure, at least during the collection process. Furthermore, there is no more risk to recipients of plasma products from frequent donors than from occasional donors. It would seem that the ambient level of DEHP to be expected in stored frozen plasma products averages no greater than about 0.5 ppm.

Storage of platelet concentrates--an in vitro study of four types of plastic packs.

Four types of plastic blood collection packs were studied for their ability to preserve platelet function during a 5 d storage period. The platelet concentrates were stored in polyvinyl chloride (Tuta Laboratories), PL 1240 and PL 732 (Fenwal Laboratories) and CLX (Cutter Laboratories) packs, on a Fenwal elliptical rotator at 20 degrees-24 degrees C. Plasma pH, lactate concentration, hypotonic shock response (HSR), platelet aggregation in response to ADP, collagen and ristocetin and levels of the plasticisers, di-2-ethylhexyl phthalate (DEHP) and tri-ethylhexyl trimellitate (TEHTM), were measured. Morphological changes were assessed by electron microscopy. No significant fall in pH occurred in any type of pack but in vitro function and platelet morphology was generally better preserved in Tuta and CLX packs than in PL 732 and PL 1240. Very little TEHTM leached out of the PL 1240 and CLX packs whereas the mean concentration of DEHP in the platelet concentrates stored in Tuta packs was 27.4 mg/100 ml plasma after 5 d of storage. The results indicate that it is possible to prepare and store platelet concentrates in polyvinyl chloride plastic packs for a period of 5 d and maintain their function and viability.

Incorporation of plasticizer into red cells during storage.

The development of flexible plastic blood bags has permitted effective blood component production and therapy. However, the plasticizer di(2-ethylhexyl)phthalate (DEHP), whose toxicity in humans is still undefined, is known to leach from the plastic into stored blood. Despite the availability of bags made of plastics not using DEHP, the collection and storage of red cells is still done in DEHP plasticized packs, and in fact the storage life for red cells has recently been increased up to 49 days using new anticoagulant-preservative solutions. We examined the relationship between DEHP and stored red cells. We found that 28 percent of available 14C-DEHP binds immediately to sites in both the membrane and cytosol fractions of the red cells, and that the total amount and distribution of 14C-DEHP does not change significantly over 7 days. When red cell concentrates were stored with or without DEHP, using either plastic (polyolefin) bags not containing DEHP or glass, definite reduction in the osmotic stability of the red cells was found in the absence of DEHP. Plasma-free hemoglobin levels were 90.3 mg per dl after 35 days of storage in plastic packs containing DEHP and 181.7 mg per dl in the polyolefin bags. The advantages of improved in vitro stability of red cells stored in plastics containing DEHP must be weighed against the potential hazards of patient exposure to DEHP.

Gas chromatographic--mass spectrometric detection of circulating plasticizers in surgical patients.

Gas chromatographic and gas chromatographic--mass spectrometric analytical techniques were employed to quantitate and confirm levels of circulating organic plasticizers in critically ill surgical patients. Two plasticizers, dibutyl phthalate (DBP) and di-(2-ethylhexyl) phthalate (DEHP), have been identified. DEHP can be found in many plastic medical devices. The DEHP levels were significant soon after transfusion or in the presence of renal dysfunction. The source of DBP is not clear at present and requires further study. The prevention of this contamination and the toxicity of these plasticizers should be investigated to ensure the safe use of plastic medical devices.

Phthalate interference in gas-chromatographic determination of long-chain fatty acids in plasma.

Phthalates leached from plastic tubing or other plastic devices may interfere with gas-chromatographic determination of long-chain fatty acids in plasma. In the case of hospitalized patients who have received infusions or had blood drawn through plastic tubing, gas chromatography/mass spectrometry may be required for accurate determination of such fatty acids.

Plasma protein binding of basic drugs. I. Selective displacement from alpha 1-acid glycoprotein by tris(2-butoxyethyl) phosphate.

The protein binding of a number of basic drugs has been shown to be inhibited when blood is collected in Vacutainer tubes. We found that the plasticizer tris(2-butoxyethyl) phosphate (TBEP), present in plasma collected in Vacutainers, was a potent inhibitor of alprenolol and imipramine protein binding. Its concentration in the plasma could quantitatively explain the displacement phenomenon. Alprenolol binding to a solution of a physiologic concentration (0.67 gm/L, 0.015 mM) of alpha 1-acid glycoprotein (orosomucoid) was decreased from 75% to 16% by addition of 10 microgram/ml (0.026 mM) of TBEP, while imipramine binding was decreased from 69% to 13%. Alprenolol and imipramine binding to albumin and lipoproteins was virtually unchanged by TBEP. Due to its selective effect on binding to alpha 1-acid glycoprotein, TBEP may be a useful tool for studying plasma protein binding of basic drugs.

The release of plasticizer from polyvinyl chloride haemodialysis tubing.

The extent of migration of plasticizer from haemodialysis lines into saline and plasma has been examined and a number of different types of tubing have been compared. A model system designed to simulate in vivo haemodialysis was evolved. The method uses a continuous cyclohexane extraction in order to mimic uptake of plasticizer by body tissues. Although not an ideal system, the results obtained are indicative of the extent to which the plasticizers are leached.

Determination of plasticizer levels in serum of hemodialysis patients.

Serum DEHP levels were measured on 27 hemodialysis patients at various time intervals. The following results were obtained: 1) Predialysis levels of DEHP occurred in only one of 22 samples. 2) Postdialysis serum levels reached a mean of 751 nGm DEHP/ml serum. 3) Samples from patients with less than 50 hemodialysis treatments gave a mean of 558 nGm/ml, while those with more than 50 treatments gave a mean of 973 nGM/ml. These numbers were found to be significantly different at a 95% confidence level. 4) No difference in DEHP levels were found for males and females. 5) The appearance of DEHP during dialysis and its disappearance after dialysis were found to be biphasic. 6) No correlation was found between serum DEHP and triglyceride levels in postdialysis serum samples.