Migration of di(2-ethylhexyl) phthalate, diisononylcyclohexane-1,2-dicarboxylate and di(2-ethylhexyl) terephthalate from transfusion medical devices in labile blood products: A comparative study

Abstract

Background and objectives: Polyvinyl chloride (PVC) plasticized with di(2-ethylhexyl) phthalate (DEHP) is a widely used material for medical transfusion devices. Not covalently bound to PVC, DEHP can migrate into blood products during storage. Recognized as an endocrine disruptor and raising concerns about its potential carcinogenicity and reprotoxicity, DEHP is gradually being withdrawn from the medical device market. Therefore, the use of alternative plasticizers, such as diisononylcyclohexane-1,2-dicarboxylate (DINCH) and di(2-ethylhexyl) terephthalate (DEHT), as potential candidates for the replacement of DEHP in medical transfusion devices has been investigated. The purpose of this study was to evaluate the quantity of PVC-plasticizers in the blood components according to their preparation, storage conditions and in function of the plasticizer.

Materials and methods: Whole blood was collected, and labile blood products (LBPs) were prepared by the buffy-coat method with a PVC blood bag plasticized either with DEHP, DINCH or DEHT. DINCH and DEHT equivalent concentrations were quantified in LBPs by liquid chromatography-tandem mass spectrometry or coupled with UV and compared to DEHP equivalent concentrations.

Results: The plasticizer equivalent concentration to which a patient is exposed during a transfusion depends on the preparation of LBPs as well as their storage conditions, that is, temperature and storage time. At day 1, for all LBPs, the migration of DEHP is 5.0 and 8.5 times greater than DINCH and DEHT, respectively. At the end of the 49 days storage period, the DEHP equivalent concentration in red blood cells concentrate is statistically higher when compared to DINCH and DEHT, with maximal values of 1.85, 1.13 and 0.86 μg/dm² /mL, respectively.

Conclusion: In addition to lower toxicity, transfused patients using PVC-DEHT or PVC-DINCH blood bags are less exposed to plasticizers than using PVC-DEHP bags with a ranging exposure reduction from 38.9% to 87.3%, due to lower leachability into blood components.

Keywords: di(2-ethylhexyl) phthalate; di(2-ethylhexyl) terephthalate; diisononylcyclohexane-1,2-dicarboxylate; labile blood product; metabolites; plasticizer migration.