title: Absorption and metabolism of the food contaminant 3-chloro-1,2-propanediol (3-MCPD) and its fatty acid esters by human intestinal Caco-2 cells.
abstract: 3-Chloro-1,2-propanediol (3-MCPD) fatty acid esters are formed upon thermal processing of fat-containing foods in the presence of chloride ions. Upon hydrolytic cleavage, these substances could release free 3-MCPD. This compound is toxicologically well characterised and displayed cancerogenic potential in rodent models. Recently, serious contaminations of different food products with 3-MCPD fatty acid esters have been reported. In regard to a risk assessment, the key question is to which degree these 3-MCPD fatty acid esters are hydrolysed in the human gut. Therefore, the aim of the present project was to examine the hydrolysis of 3-MCPD fatty acid esters and the resulting release of free 3-MCPD by using differentiated Caco-2 cells, a cellular in vitro model for the human intestinal barrier. Here, we show that 3-MCPD fatty acid esters at a concentration of 100 μM were neither absorbed by the cells nor the esters were transported via a Caco-2 monolayer. 3-MCPD-1-monoesters were hydrolysed in the presence of Caco-2 cells. In contrast, a 3-MCPD-1,2-diester used in this study was obviously absorbed and metabolised by the cells. Free 3-MCPD was not absorbed by the cells, but the substance migrated through a Caco-2 monolayer by paracellular diffusion. From these in vitro studies, we conclude that 3-MCPD-1-monoesters are likely to be hydrolysed in the human intestine, thereby increasing the burden with free 3-MCPD. In contrast, intestinal cells seem to have the capacity to metabolise 3-MCPD diesters, thereby detoxifying the 3-MCPD moiety.
authors.affiliation: Department of Food Safety, Federal Institute For Risk Assessment, Thielallee 88-92, 14195 Berlin, Germany. thorsten.buhrke@bfr.bund.de
authors.forename: Thorsten
authors.initials: T
authors.lastname: Buhrke
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Weisshaar
authors.forename: Alfonso
authors.initials: A
authors.lastname: Lampen
mesh_terms: D018938:Caco-2 Cells; D004952:Esters / Q000378:metabolism; D005506:Food Contamination; D005990:Glycerol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D006801:Humans; D006868:Hydrolysis; D008658:Inactivation, Metabolic; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D008049:Lipase / Q000378:metabolism; D000517:alpha-Chlorohydrin
chemical_list: D004952:Esters; D000517:alpha-Chlorohydrin; D008049:Lipase; D005990:Glycerol