In silico Toxizitätsvorhersage der hitzebedingten Lebensmittelkontaminanten 3-MCPD, 2-MCPD und 2-MCPD-Dipalmitat und anschließende vergleichende proteomische Analyse substanzinduzierter molekularer Veränderungen in Leber, Niere, Hoden und Herz der Ratte

The detection of numerous Maillard reaction and lipid oxidation products in a variety of processed food such as grilled meat, coffee, edible plant oils and heated cereals did put a lot of pressure on federal consumer protection authorities. Due to the lack of sufficient data regarding toxicological characteristics, an adequate risk assessment for numerous heat-induced food contaminants is not possible. Therefore the possibilities of in silico predictions regarding the endpoints mutagenicity and cancerogenicity based on (quantitative) structure activity relationship (QSAR) was examined for more than 800 substances. For this approach, five software tools for mutagenicity prediction and three carcinogenicity prediction tools were used, all of them beeing freely available. The combination of the software tool output yielded a mutagenicity score or carcinogenicity score, which can be seen as a kind of putative toxicity index. A subsequent inquiry revealed good correlation between in silico prediction and available experimental data. For the substances 3-monochloro-1,2-propanediol (3-MCPD) and 2-monochloro-1,3-propanediol (2-MCPD), which were found amongst the top 10 rated compounds regarding the endpoint mutagenicity, a proteomic approach using a subacute 28-day toxicity study on male Wistar rats was issued to find out more about their toxicological characteristics. Despite their structural similarities, there was only small commonality of deregulated proteins between the chloropropanoles. Regardless of this, 2-MCPD and 3-MCPD showed similar toxic effects. The mechanism behind remains unrevealed. In addition, it was shown that 2-MCPD esterified with palmitic acid caused similar effects on the organs focused on in the current study indicating a release of free 2-MCPD. Possible synergistic effects based on real life mixtures of the substances examined in this study demand their discovery.