Human toxicokinetics of [13C4]-Furan and investigation of exogenous and endogenous sources of background excretion of putative biomarkers of furan exposure as a basis for biomarker-based exposure assessment of furan in food

• Applicant: Professorin Dr. Angela Mally
• Subject Area: Toxicology, Laboratory Medicine
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 437639884

Reliable exposure assessment is essential for risk assessment of furan in food. Assessment of human exposure based on the furan content in foods is, however, subject to uncertainty. Biomarker monitoring is thus considered an alternative or complementary approach to furan exposure assessment. Toxicokinetic studies in rats and initial investigations in human volunteers support biomarker monitoring as a suitable approach to furan exposure assessment. In particular, the cyclic glutathione conjugate of the reactive furan metabolite cis-butene-1,4-dial (BDA), GSH-BDA, appears to present a suitable biomarker of furan exposure. In contrast, high urinary background levels of several other furan metabolites observed both in rats and humans questions the use of these metabolites as markers of exposure. The source for this background (endogenous vs. exogenous) remains unclear. Probable daily intakes estimated from GSH-BDA in human volunteers and urinary excretion rates of GSH-BDA in rats closely match exposures estimates based on occurrence and food consumption data, although some uncertainties remain due to potential species- and gender-differences in the excretion rates of GSH-BDA. With the overall objective of improving biomarker-based exposure assessment of furan by addressing remaining uncertainties, this project will investigate human toxicokinetics of isotopically labeled furan to accurately define metabolite excretion rates in humans for more precise exposure estimates, and further explore exogenous and endogenous sources of the background excretion of furan metabolites in humans and experimental animals. To this end, selected food items and animal feed will be subject to simulated digestion during passage through the gastrointestinal tract an analyzed for the presence of furan metabolites and putative precursors that may form during food processing. The possibility of endogenous formation of furan or its metabolites during normal physiological processes or during conditions of cell stress (e.g. lipid peroxidation, 5´-oxidation of deoxyribose) will be investigated in cell culture. It is expected that the outcome of the work will allow scientifically valid conclusions regarding the value of furan metabolites as biomarkers of exposure.

• DFG Programme: Research Grants