Fatty acid esters of 2-/3-monochloropropanediol (MCPD) and glycidol are heat-induced food contaminants formed during vegetable fat deodorization. Gastrointestinal hydrolysis leads to uptake of free 2-/3-MCPD or glycidol. A group TDI of 2 µg/kg bw/day for 3-MCPD and its esters was recently derived by the EFSA.<br/>A combined proteomic and transcriptomic approach was conducted based on a 28-day rat feeding study to examine the molecular mechanism(s) of 2-/3-MCPD toxicity. 3-MCPD impaired glycolysis and impacted glutathione metabolism and redox homeostasis especially in kidney and testes. The investigated molecular targets of the MCPD isomers were different.  Of note, the redox sensor protein DJ-1 was oxidized and thus irreversibly inactivated by 3-MCPD. Loss of function of DJ-1 is associated with oxygen stress-related diseases such as Parkinson’s disease or type II diabetes. 3-MCPD-induced formation of reactive oxygen species (ROS) was confirmed in a study with so-called HOTT reporter mice, which express a lacZ transgene under the control of the ROS-sensitive heme oxygenase promoter. LacZ staining of tissue slides revealed a high ROS burden in kidney, testes and some brain regions following 3-MCPD exposure. Thus, 3-MCPD toxicity appears to be predominantly associated with ROS formation.<br/>Furthermore, a UPLC-MS/MS method was developed to quantify hemoglobin adducts of glycidol from blood samples, in order to establish a human biomarker for the internal exposure. It was used to monitor the increase from the background mean of 3.3 to the level of 9.8 pmol adducts/g hemoglobin in twelve volunteers which consumed a daily portion of 35 g of commercially available palm fat (8.7 mg glycidol/kg) over four weeks. In the following wash-out phase the adduct levels dropped to the starting levels within 15 weeks, corresponding to the lifespan of human erythrocytes. A model describing the observed kinetics was developed for future estimation of glycidol exposure from blood samples.

MCPD and glycidyl fatty acid esters: Molecular mechanisms of toxicity and new human exposure marker for biomonitoring

256th National Meeting (2018)

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