title: In vitro cytotoxic effects of DEHP-alternative plasticizers and their primary metabolites on a L929 cell line.
abstract: Phthalic acid esters have been widely used to improve the plasticity of PVC medical devices. They carry a high exposure risk for both humans and the environment in clinical situations. Our study focuses on the cytotoxicity of alternative plasticizers. Postulated primary metabolites were synthesized, not being commercially available. Cytotoxicity assays were performed on L929 murine cells according to the ISO-EN 10993-5 standard design for the biocompatibility of medical devices. The tested concentrations of plasticizers (0.01, 0.05 and 0.1 mg/ml) covered the range likely to be found in biological fluids coming into direct contact with the medical devices. DEHP, DINP and DINCH were cytotoxic at the highest concentration (0.1 mg/ml) for 7 days of exposure. Their corresponding metabolites were found to be more cytotoxic, for the same concentration. By contrast, TOTM and its corresponding metabolite MOTM were not found to be cytotoxic. DEHA showed no cytotoxicity, but its corresponding monoester (MEHA) produced a cytotoxic effect at 0.05 mg/ml. In clinical situations, medical devices can release plasticizers, which can come into contact with patients. In vivo, the plasticizers are quickly transformed into primary metabolites. It is therefore important to measure the effects of both the plasticizers and their corresponding metabolites. Standard first-line cytotoxicity assays should be performed to ensure biocompatibility.
authors.affiliation: Université Clermont Auvergne, INSERM, U1240 Imagerie Moléculaire et Stratégies Théranostiques, F-63000 Clermont Ferrand, France; CHU Clermont-Ferrand, Pôle Pharmacie, rue Montalembert, 63003 Clermont-Ferrand, France.
authors.forename: Teuta
authors.initials: T
authors.lastname: Eljezi
authors.affiliation: France Université de Nantes, INSERM, U791, LIOAD, Nantes, F-44042, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Pinta
authors.affiliation: Service de Pharmacologie, Hôpital Gabriel-Montpied, CHU de Clermont-Ferrand, Clermont-Ferrand, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Richard
authors.affiliation: Service de Pharmacologie, Hôpital Gabriel-Montpied, CHU de Clermont-Ferrand, Clermont-Ferrand, France.
authors.forename: Jérémy
authors.initials: J
authors.lastname: Pinguet
authors.affiliation: Université Clermont Auvergne, INSERM, U1240 Imagerie Moléculaire et Stratégies Théranostiques, F-63000 Clermont Ferrand, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Chezal
authors.affiliation: Nutrition Physiology and Toxicology Team (NUTox), UMR U866 INSERM, Université de Bourgogne Franche-Comté, AgroSup Dijon, 1 Esplanade Erasme, 21000 Dijon, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Chagnon
authors.affiliation: CHU Clermont-Ferrand, Pôle Pharmacie, rue Montalembert, 63003 Clermont-Ferrand, France; Clermont Université, Université d'Auvergne, EA 4676C-BIOSENSS, 63000 Clermont-Ferrand, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Sautou
authors.affiliation: France Université de Nantes, INSERM, U791, LIOAD, Nantes, F-44042, France.
authors.forename: Gaël
authors.initials: G
authors.lastname: Grimandi
authors.affiliation: Université Clermont Auvergne, INSERM, U1240 Imagerie Moléculaire et Stratégies Théranostiques, F-63000 Clermont Ferrand, France. Electronic address: emmanuel.moreau@udamail.fr.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Moreau
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D004051:Diethylhexyl Phthalate / Q000009:adverse effects* / Q000378:metabolism; D004952:Esters / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology*; D066298:In Vitro Techniques; D051379:Mice; D010795:Phthalic Acids / Q000378:metabolism; D010968:Plasticizers / Q000009:adverse effects* / Q000378:metabolism; D011143:Polyvinyl Chloride / Q000378:metabolism
chemical_list: D004952:Esters; D010795:Phthalic Acids; D010968:Plasticizers; D011143:Polyvinyl Chloride; D004051:Diethylhexyl Phthalate
keywords: Cytotoxicity; DEHP-alternative plasticizers; Metabolite synthesis; Phthalates; Plasticizers