US EPA

3540853 

Journal Article 

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

Eljezi, T; Pinta, P; Richard, D; Pinguet, J; Chezal, JM; Chagnon, MC; Sautou, V; Grimandi, G; Moreau, E 

2017 

Yes 

Chemosphere
ISSN: 0045-6535
EISSN: 1879-1298 

PERGAMON-ELSEVIER SCIENCE LTD 

OXFORD 

173 

Elsevier 

452-459 

English 

28129623 

10.1016/j.chemosphere.2017.01.026 

WOS:000395213700052 

https://search.proquest.com/docview/1862764170?accountid=171501
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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. 

Animals; Cell Survival/drug effects; Cells, Cultured; Diethylhexyl Phthalate/adverse effects/metabolism; Esters/metabolism; Fibroblasts/drug effects/pathology; In Vitro Techniques; Phthalic Acids/metabolism; Plasticizers/adverse effects/metabolism; Polyvinyl Chloride/metabolism; Cytotoxicity; DEHP-alternative plasticizers; Metabolite synthesis; Phthalates; Plasticizers