title: 2-Chloro-1,3-propanediol (2-MCPD) and its fatty acid esters: cytotoxicity, metabolism, and transport by human intestinal Caco-2 cells.
abstract: The food contaminants 3-chloro-1,2-propanediol (3-MCPD) and 3-MCPD fatty acid esters have attracted considerable attention in the past few years due to their toxic properties and their occurrence in numerous foods. Recently, significant amounts of the isomeric compounds 2-chloro-1,3-propanediol (2-MCPD) fatty acid esters have been detected in refined oils. Beside the interrogation which toxic effects might be related to the core compound 2-MCPD, the key question from the risk assessment perspective is again-as it was discussed for 3-MCPD fatty acid esters before-to which degree these esters are hydrolyzed in the gut, thereby releasing free 2-MCPD. Here, we show that free 2-MCPD but not 2-MCPD fatty acid esters were able to cross a monolayer of differentiated Caco-2 cells as an in vitro model for the human intestinal barrier. Instead, the esters were hydrolyzed by the cells, thereby releasing free 2-MCPD which was neither absorbed nor metabolized by the cells. Cytotoxicity assays revealed that free 2-MCPD as well as free 3-MCPD was not toxic to Caco-2 cells up to a level of 1 mM, whereas cellular viability was slightly decreased in the presence of a few 2-MCPD and 3-MCPD fatty acid esters at concentrations above 10 µM. The observed cytotoxic effects correlated well with the induction of caspase activity and might be attributed to the induction of apoptosis by free fatty acids which were released from the esters in the presence of Caco-2 cells.
authors.affiliation: Department of Food Safety, Federal Institute for Risk Assessment, Max-Dohrn-Str. 8-10, 10589, Berlin, Germany. thorsten.buhrke@bfr.bund.de.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Buhrke
authors.affiliation: Department of Food Safety, Federal Institute for Risk Assessment, Max-Dohrn-Str. 8-10, 10589, Berlin, Germany.
authors.forename: Falko
authors.initials: F
authors.lastname: Frenzel
authors.affiliation: SGS Germany GmbH, Weidenbaumsweg 137, 21035, Hamburg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Kuhlmann
authors.affiliation: Department of Food Safety, Federal Institute for Risk Assessment, Max-Dohrn-Str. 8-10, 10589, Berlin, Germany.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Lampen
mesh_terms: D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004952:Esters; D005227:Fatty Acids / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D006801:Humans; D006868:Hydrolysis; D007408:Intestinal Absorption; D018570:Risk Assessment; D000517:alpha-Chlorohydrin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*
chemical_list: D004952:Esters; D005227:Fatty Acids; D000517:alpha-Chlorohydrin
keywords: 2-MCPD; 3-MCPD; Caco-2; Fatty acid ester; Food contaminant; Risk assessment