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 N^α-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.

呋喃是加热处理食品中的肝脏有毒物质和致癌物质。由于其挥发性，对食品中呋喃的分析不能提供可靠的暴露估计。基于生物标志物的方法为更准确地评估人体暴露提供了机会，但尚未确定呋喃暴露的潜在生物标志物浓度与外部剂量之间的相关性。

呋喃的生物活化以及顺式-2-丁烯-1,4-二聚体（BDA）与细胞亲核试剂的后续反应产生了一系列代谢产物，可作为呋喃暴露的生物标记。在这项研究中，N- [4-羧基-4-（3-巯基-1H-吡咯-1-基）-1-氧丁基] -L-半胱氨酰甘氨酸环状硫化物，BDA的单谷胱甘肽加合物（GSH-BDA）和R-2-乙酰基-6-（2,5-二氢-2-氧代-1H-吡咯-1-基）-1-己酸，BDA与N-加合物^α -乙酰基-L-赖氨酸（NAcLys合成并通过LC-MS / MS在0、0.1、0.5和2.0 mg / kg bw的呋喃溶液中处理5天和28天的大鼠尿液中进行LC-MS / MS分析。

GSH-BDA和NAcLys-BDA均以剂量相关的方式排泄。GSH-BDA的24小时排泄率介于给药剂量的0.6％至1.1％之间，NAcLys-BDA的排泄率为1.4％至2.1％。与GSH-BDA相比，NAcLys-BDA也存在于对照组的尿液中，表明是内源性形成或背景暴露。

总体而言，尿中呋喃代谢物与外部剂量之间的密切相关性为基于生物标记物的方法监测人体暴露于呋喃提供了实验支持。