title: Screening study on hemolysis suppression effect of an alternative plasticizer for the development of a novel blood container made of polyvinyl chloride.
abstract: The aim of this study is to identify a plasticizer that is effective in the suppression of the autohemolysis of the stored blood and can be used to replace di(2-ethylhexyl) phthalate (DEHP) in blood containers. The results of hemolysis test using mannitol-adenine-phosphate/red cell concentrates (MAP/RCC) spiked with plasticizers included phthalate, phthalate-like, trimeliate, citrate, and adipate derivatives revealed that di-isononyl-cyclohexane-1,2-dicarboxylate (Hexamoll(®) DINCH), di(2-ethylhexyl)-1,2,3,6-tetrahydro-phthalate (DOTP), and diisodecyl phthalate (DIDP) exhibited a hemolysis suppression effect almost equal to that of DEHP, but not other plasticizers. This finding suggested that the presence of 2 carboxy-ester groups at the ortho position on a 6-membered ring of carbon atoms may be required to exhibit such an effect. The hemolytic ratios of MAP/RCC-soaked polyvinyl chloride (PVC) sheets containing DEHP or different amounts of DINCH or DOTP were reduced to 10.9%, 9.2-12.4%, and 5.2-7.8%, respectively (MAP/RCC alone, 28.2%) after 10 weeks of incubation. The amount of plasticizer eluted from the PVC sheet was 53.1, 26.1-36.5, and 78.4-150 µg/mL for DEHP, DINCH, and DOTP, respectively. PVC sheets spiked with DIDP did not suppress the hemolysis induced by MAP/RCC because of low leachability (4.8-6.0 µg/mL). These results suggested that a specific structure of the plasticizer and the concentrations of least more than ∼10 µg/mL were required to suppress hemolysis due to MAP/RCC.
authors.affiliation: Division of Medical Devices, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Haishima
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kawakami
authors.forename: Chie
authors.initials: C
authors.lastname: Hasegawa
authors.forename: Akito
authors.initials: A
authors.lastname: Tanoue
authors.forename: Toshiyasu
authors.initials: T
authors.lastname: Yuba
authors.forename: Kazuo
authors.initials: K
authors.lastname: Isama
authors.forename: Atsuko
authors.initials: A
authors.lastname: Matsuoka
authors.forename: Shingo
authors.initials: S
authors.lastname: Niimi
mesh_terms: D000225:Adenine; D001565:Benzoates / Q000494:pharmacology; D001793:Blood Preservation / Q000295:instrumentation*; D002951:Citrates; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D003864:Depression, Chemical; D003998:Dicarboxylic Acids / Q000494:pharmacology; D004051:Diethylhexyl Phthalate / Q000494:pharmacology / Q000633:toxicity; D008401:Gas Chromatography-Mass Spectrometry; D005947:Glucose; D006461:Hemolysis / Q000187:drug effects*; D006493:Heparin; D006801:Humans; D007292:Inosine Nucleotides / Q000494:pharmacology; D008353:Mannitol; D010080:Oxazoles / Q000494:pharmacology; D010968:Plasticizers / Q000737:chemistry / Q000494:pharmacology*; D011143:Polyvinyl Chloride; D011744:Pyrimidinones / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D001565:Benzoates; D002951:Citrates; D003509:Cyclohexanecarboxylic Acids; D003998:Dicarboxylic Acids; D007292:Inosine Nucleotides; D010080:Oxazoles; D010968:Plasticizers; D011744:Pyrimidinones; C549898:deoxyinosine diphosphate; C558012:diisononyl 1,2-cyclohexanedicarboxylic acid; C063359:2,3-dihydro-5H-oxazolo(3,2-a)thieno(3,2-d)pyrimidin-5-one; D008353:Mannitol; C007077:citrate phosphate dextrose; D011143:Polyvinyl Chloride; D006493:Heparin; C034367:trioctyl trimellitate; D004051:Diethylhexyl Phthalate; D005947:Glucose; D000225:Adenine
keywords: DEHP; PVC medical device; alternative plasticizer; blood container; hemolysis