Evaluation of a biomarker-based approach for exposure assessment of furan in food

呋喃存在于各种经过热处理的食品中。由于呋喃的高挥发性和对家庭烹饪过程中呋喃的命运的了解有限，基于食品消费数据和食品中呋喃含量的人体暴露评估是不可靠的。考虑到目前的暴露估计值与对实验动物造成不利健康影响的呋喃剂量之间的差距很小，迫切需要改进暴露评估，作为风险评估的基础。考虑到呋喃可能内源性形成的影响，该项目的总体目标是测试基于生物标志物的方法的有效性，以评估通过食物接触呋喃的情况。同位素标记的[3,4- 13c]-呋喃在大鼠的大剂量范围内（包括与人类暴露相关的剂量）施用，将使我们能够精确地建立外源剂量与尿液中呋喃代谢物浓度之间的相关性，并区分内源性形成和通过饲料摄入呋喃。这些实验将提供关键信息，说明哪些代谢物（单独的或组合的）可能适合评估在实际暴露情景下对呋喃的暴露。作为概念验证，在食用呋喃含量低与高的食物后，将对人类志愿者尿液中的潜在呋喃暴露生物标志物进行定量分析，以估计暴露程度。

Furan occurs in a variety of food items that undergo heat treatment. Due to the high volatility of furan and limited understanding of the fate of furan during home cooking, assessment of human exposure based on food consumption data and furan content in food is unreliable. Considering the low margin between current exposure estimates and furan doses that cause adverse health effects in laboratory animals, there is an urgent need for improved exposure assessment as a basis for risk assessment.Taking into account the contribution of possible endogenous formation of furan, the overall aim of the project is to test the validity of a biomarker-based approach to assess exposure to furan via food. Administration of isotopically labelled [3,4-13C]-Furan to rats across a wide dose range that includes doses relevant to human exposure will allow us to precisely establish the correlation between external dose and concentration of furan metabolites in urine over time and to discriminate against endogenous formation and furan intake via feed. These experiments will provide critical information as to which metabolites (isolated or in combination) may be suitable to assess exposure to furan under realistic exposure scenarios. As proof-of-concept, potential biomarkers of furan exposure will be quantitatively analysed in urine of human volunteers following consumption of food with low vs. high furan content to estimate exposure.