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Furan and 2-methylfuran (2-MF) can form during food processing and accumulate in foods at various concentrations depending on processing technology and beverage/meal preparation methods applied prior to consumption. Here, we report a controlled dosimetry study with 20 volunteers (10 male, 10 female) to monitor dietary furan/2-MF exposure. The volunteers followed an eleven-day furan/2-MF-restricted diet in which they consumed freshly prepared coffee brew containing known amounts of furan and 2-MF on two separate occasions (250 mL and 500 mL on days 4 and 8, respectively). Urine was collected over the whole study period and analyzed for key metabolites derived from the primary oxidative furan metabolite cis -2-butene-1,4-dial (BDA) (i.e., Lys-BDA, AcLys-BDA and cyclic GSH-BDA) and the primary 2-MF metabolite acetylacrolein (AcA, 4-oxo-pent-2-enal) (i.e., Lys-AcA and AcLys-AcA). A previously established stable isotope dilution analysis (SIDA) method was utilized. Excretion kinetics revealed two peaks (at 0–2 and 24–36 h) for AcLys-BDA, Lys-BDA, AcLysAcA and LysAcA, whereas GSH-BDA showed a single peak. Notably, women on average excreted the metabolite GSH-BDA slightly faster than men, indicating gender differences. Overall, the study provided further insights into the spectrum of possible biomarkers of furan and 2-methyfuran metabolites occurring in the urine of volunteers after coffee consumption. [Display omitted] • We have performed a duplicate diet intervention study. • Volunteers consumed a furan/2-methylfuran reduced diet. • Urine samples and meal duplicates were collected. • Furan/2-methylfuran were analyzed in meals and coffee beverage. • Biomarkers of excretion were identified and quantitated. [ABSTRACT FROM AUTHOR]

Furan is a liver toxicant and carcinogen that occurs in heat-processed foods. Due to its volatility, analysis of furan in food does not provide reliable estimates of exposure. Biomarker-based approaches offer the opportunity to more accurately assess human exposure, but a correlation between concentrations of potential biomarkers of furan exposure and external dose has not been established. Bioactivation of furan and subsequent reaction of cis-2-butene-1,4-dial (BDA) with cellular nucleophiles gives rise to a range of metabolites that may serve as biomarkers of furan exposure. In this study, N-[4-carboxy-4-(3-mercapto-1H-pyrrol-1-yl)-1-oxobutyl]-L-cysteinylglycine cyclic sulfide, a mono-glutathione adduct of BDA (GSH-BDA), and R-2-acetylamino-6-(2,5-dihydro-2-oxo-1H-pyrrol-1-yl)-1-hexanoic acid, an adduct of BDA with Nα-acetyl-L-lysine (NAcLys-BDA), were synthesized and analysed by LC-MS/MS in urine of rats treated with furan at 0, 0.1, 0.5 and 2.0 mg/kg bw for 5 and 28 days. GSH-BDA and NAcLys-BDA were both excreted in a dose-related manner. 24 h excretion rates ranged between 0.6 and 1.1% of the administered dose for GSH-BDA, and 1.4–2.1% for NAcLys-BDA. In contrast to GSH-BDA, NAcLys-BDA was also present in urine of controls, suggesting either endogenous formation or background exposure. Overall, the close correlation between urinary furan metabolites and external dose provides experimental support for biomarker-based approaches to monitor human exposure to furan. • Assessment of human exposure based furan content in food is unreliable. • The relationship between furan exposure and potential biomarkers of furan exposure was established in the rat model. • Adducts of cis -2-butene-1,4-dial with glutathione and lysine were quantified in rat urine using LC-MS/MS. • Urinary furan metabolites were excreted in a dose-related manner. • The study provides experimental support for biomarker-based approaches to monitor human exposure to furan. [ABSTRACT FROM AUTHOR]