Visintin Lia, Martino Camilla, De Saeger Sarah, Alladio Eugenio, De Boevre Marthe, Chiu Weihsueh A
Centre of Excellence in Mycotoxicology and Public Health, Faculty of Pharmaceutical Sciences, Ghent University, 9000 Ghent, Belgium.
Doping Control Laboratory, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium.
Toxins (Basel). 2025 Jul 31;17(8):382. doi: 10.3390/toxins17080382.
Citrinin (CIT) is a mycotoxin produced by various fungi contaminating stored cereals and fruits. While biomonitoring and food occurrence data indicate widespread exposure, its public health risks remain unclear due to the lack of human toxicokinetic (TK) data.
A UHPLC-MS/MS method was validated for CIT quantification in capillary blood (VAMS Mitra tips), feces, and urine obtaining LLOQs ≤ 0.05 ng/mL. A human TK study was conducted following a single oral bolus of 200 ng/kg bw CIT. Individual capillary blood (VAMS Mitra tips), feces, and urine samples were collected for 48 h after exposure. Samples were analyzed to determine CIT's TK profile.
TK modeling was performed using a multi-compartmental structure with a hierarchical Bayesian population approach, allowing robust parameter estimation despite the lack of standards for CIT metabolites.
The derived TK parameters align with preliminary human data and significantly advance CIT exposure assessment via biomonitoring. A human inter-individual toxicokinetic variability (HK) of 1.92 was calculated based on the derived AUC, indicating that EFSA's current default uncertainty factor for TK variability is adequately protective for at least 95% of the population.
桔霉素（CIT）是一种由多种污染储存谷物和水果的真菌产生的霉菌毒素。虽然生物监测和食品中出现的数据表明其暴露广泛，但由于缺乏人体毒代动力学（TK）数据，其公共卫生风险仍不明确。
验证了一种超高效液相色谱-串联质谱法用于定量测定毛细管血样（VAMS Mitra采血针）、粪便和尿液中的CIT，最低定量限≤0.05 ng/mL。在单次口服200 ng/kg体重的CIT后进行了人体TK研究。暴露后48小时收集个体毛细管血样（VAMS Mitra采血针）、粪便和尿液样本。分析样本以确定CIT的TK特征。
使用具有分层贝叶斯群体方法的多室结构进行TK建模，尽管缺乏CIT代谢物的标准品，但仍能进行可靠的参数估计。
推导得到的TK参数与初步的人体数据一致，并通过生物监测显著推进了CIT暴露评估。根据推导得到的AUC计算出人体个体间毒代动力学变异性（HK）为1.92，表明欧洲食品安全局目前默认的TK变异性不确定性因素对至少95%的人群具有充分的保护作用。
