Biomonitoring of heat-induced food contaminants: In vivo metabolism and excretion kinetics of alkylfurans to define biomarkers of exposure

• Applicant: Professorin Dr. Angela Mally
• Subject Area: Toxicology, Laboratory Medicine
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 517627564

Thermal treatment of food can lead to the formation of a wide range of process-related food contaminants. Besides furan, a potent hepatotoxin and liver carcinogen that has been extensively investigated, several alkyl-substituted furans (e.g. 2-methylfuran, 2,5 dimethylfuran, 2-ethylfuran and 2-pentylfuran) are now known to be present in heat-treated foods at levels close to or even exceeding those of furan. Although occurrence data on alkylated furans are still extremely limited, these data suggest that alkylfurans may substantially contribute to dietary exposure to furans and thus to human health risks related to the presence of furans in food. Considering that dietary exposure to furan alone is considered a health concern, as highlighted by the narrow margins of exposure between estimated human exposure to furan and neoplastic and non-neoplastic effects of furan in experimental animals, there is a need to better define human exposure to alkyl-substituted furans via food as a basis for risk assessment. Biomarker monitoring has been suggested as a promising approach to exposure assessment of process-related food contaminants including furans, yet studies on in vivo biotransformation and toxicokinetics of alkyl-substituted furans to allow identification and validation of alkyl-substituted furan metabolites as biomarkers of exposure are lacking. Building on our recent work on biomarkers of furan exposure, the overall objective of this proposal is to establish a multi-biomarker LC-MS/MS method covering a range of furan and alkyl-substituted furan metabolites to enable exposure assessment of this group of structurally related process contaminants via biomarker monitoring. This will be achieved through investigating the oral toxicokinetics (OECD Test no. 417) of a series of 2-alkyl-substituted furans, which appear to significantly contribute to human (alkyl)furan exposure, in rats. Metabolites of the test compounds will be identified and characterized in urine of rats orally administered 2-methylfuran, 2-ethylfuran, 2-pentylfuran and 2,5-dimethylfuran across a wide-dose range that includes doses relevant to human exposure. Following chemical synthesis of reference compounds and stable isotope-labelled internal standards, major urinary metabolites that may serve as biomarkers of exposure will be quantitatively analyzed in order to define the correlation between biomarker concentration and exogenous exposure as a prerequisite for translating biomarker data into daily intake estimates. Biomarker monitoring in human volunteers consuming foods with high vs. low content of furans via the established multi-biomarker LC-MS/MS method will provide proof-of-concept for the validity of the biomarker-based approach for human exposure assessment.

• DFG Programme: Research Grants