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Derivation of Human Toxicokinetic Parameters and Chemical-Specific Adjustment Factor of Citrinin Through a Human
Lia Visintin1,2, Camilla Martino3, Sarah De Saeger1,4
1Centre of Excellence in Mycotoxicology and Public Health, Faculty of Pharmaceutical Sciences, Ghent University, 9000 Ghent, Belgium.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
The derived TK parameters align with preliminary human data and significantly advance CIT exposure assessment via biomonitoring. A human inter-individual toxicokinetic variability (HKAF) 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.
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