In vitro cytotoxic effects of DEHP-alternative plasticizers and their primary metabolites on a L929 cell line

被引:72
作者
Eljezi, Teuta [1 ,2 ]
Pinta, Pierre [3 ]
Richard, Damien [4 ]
Pinguet, Jeremy [4 ]
Chezal, Jean-Michel [1 ]
Chagnon, Marie-Christine [5 ]
Sautou, Valerie [2 ,6 ]
Grimandi, Gael [3 ]
Moreau, Emmanuel [1 ]
机构
[1] Univ Clermont Auvergne, INSERM, U1240 Imagerie Mol & Strategies Theranost, F-63000 Clermont Ferrand, France
[2] CHU Clermont Ferrand, Pole Pharm, Rue Montalembert, F-63003 Clermont Ferrand, France
[3] France Univ Nantes, INSERM, LIOAD, U791, F-44042 Nantes, France
[4] CHU Clermont Ferrand, Serv Pharmacol, Hop Gabriel Montpied, Clermont Ferrand, France
[5] Univ Bourgogne Franche Comte, AgroSup Dijon, Nutr Physiol & Toxicol Team NUTox, INSERM,UMR,U866, F-21000 Dijon, France
[6] Clermont Univ, Univ dAuvergne, EA 4676C BIOSENSS, Clermont Ferrand 63000, France
关键词
Plasticizers; DI-2-ETHYLHEXYL TEREPHTHALATE DEHT; NON-PHTHALATE PLASTICIZERS; PVC MEDICAL DEVICES; GC-MS; HEXAMOLL(R) DINCH(R); INHIBITS GROWTH; PPAR-GAMMA; EXPOSURE; TOXICITY; RATS;
D O I
10.1016/j.chemosphere.2017.01.026
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
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/m1) 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. (c) 2017 Elsevier Ltd. All rights reserved.
引用
收藏
页码:452 / 459
页数:8
相关论文
共 37 条
[1]   A twenty-volunteer study using deuterium labelling to determine the kinetics and fractional excretion of primary and secondary urinary metabolites of di-2-ethylhexylphthalate and di-iso-nonylphthalate [J].
Anderson, Warwick A. C. ;
Castle, Laurence ;
Hird, Simon ;
Jeffery, Jackie ;
Scotter, Michael J. .
FOOD AND CHEMICAL TOXICOLOGY, 2011, 49 (09) :2022-2029
[2]  
[Anonymous], 2009, 10993 NF EN
[3]   Migration of plasticizers from PVC medical devices: Development of an infusion model [J].
Bernard, L. ;
Cueff, R. ;
Chagnon, M. C. ;
Abdoulouhab, F. ;
Decaudin, B. ;
Breysse, C. ;
Kauffmann, S. ;
Cosserant, B. ;
Souweine, B. ;
Sautoua, V. .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2015, 494 (01) :136-145
[4]   Steroidogenesis in fetal male rats is reduced by DEHP and DINP, but endocrine effects of DEHP are not modulated by DEHA in fetal, prepubertal and adult male rats [J].
Borch, J ;
Ladefoged, O ;
Hass, U ;
Vinggaard, AM .
REPRODUCTIVE TOXICOLOGY, 2004, 18 (01) :53-61
[5]   Analysis of PVC plasticizers in medical devices and infused solutions by GC-MS [J].
Bourdeaux, Daniel ;
Yessaad, Mouloud ;
Chennell, Philip ;
Larbre, Virginie ;
Eljezi, Teuta ;
Bernard, Lise ;
Sautou, Valerie .
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, 2016, 118 :206-213
[6]   Cyclohexane-1,2-dicarboxylic acid diisononyl ester and metabolite effects on rat epididymal stromal vascular fraction differentiation of adipose tissue [J].
Campioli, Enrico ;
Duong, Tam B. ;
Deschamps, Francois ;
Papadopoulos, Vassilios .
ENVIRONMENTAL RESEARCH, 2015, 140 :145-156
[7]  
CERHR (Center for the Evaluation of Risks to Human Reproduction), 2005, NTPCERHR EXP PAN UPD
[8]   Structure-Activity Relationship of a New Series of Reversible Dual Monoacylglycerol Lipase/Fatty Acid Amide Hydrolase Inhibitors [J].
Cisneros, Jose A. ;
Bjorklund, Emmelie ;
Gonzalez-Gil, Ines ;
Hu, Yanling ;
Canales, Angeles ;
Medrano, Francisco J. ;
Romero, Antonio ;
Ortega-Gutierrez, Silvia ;
Fowler, Christopher J. ;
Lopez-Rodriguez, Maria L. .
JOURNAL OF MEDICINAL CHEMISTRY, 2012, 55 (02) :824-836
[9]   Carcinogenicity and chronic toxicity of di-2-ethylhexyl terephthalate (DEHT) following a 2-year dietary exposure in Fischer 344 rats [J].
Deyo, James A. .
FOOD AND CHEMICAL TOXICOLOGY, 2008, 46 (03) :990-1005
[10]  
ECB, 2004, EUR UN RISK ASS REP