Development of a Generic PBK Model for Human Biomonitoring with an Application to Deoxynivalenol

Toxicokinetic modelling provides a powerful tool in relating internal human exposure (i.e., assessed through urinary biomarker levels) to external exposure. Chemical specific toxicokinetic models are available; however, this specificity prevents their application to similar contaminants or to other...

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Bibliographic Details
Published in:Toxins 2023-09, Vol.15 (9), p.569
Main Authors: Notenboom, Sylvia, Hoogenveen, Rudolf T, Zeilmaker, Marco J, Van den Brand, Annick D, Assunção, Ricardo, Mengelers, Marcel J. B
Format: Article
Language:English
Subjects:
Biological monitoring
Biomarkers
Biomonitoring
Chemicals
Contaminants
Deoxynivalenol
deoxynivalenol-15-glucuronide
deoxynivalenol-3-glucuronide mycotoxin
Diet
dietary exposure
Excretion
Exposure
generic PBK modelling
human biomonitoring
Identification and classification
Inhalation
Metabolism
Metabolites
Methods
Mycotoxins
Respiration
Urine
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Summary:Toxicokinetic modelling provides a powerful tool in relating internal human exposure (i.e., assessed through urinary biomarker levels) to external exposure. Chemical specific toxicokinetic models are available; however, this specificity prevents their application to similar contaminants or to other routes of exposure. For this reason, we investigated whether a generic physiological-based kinetic (PBK) model might be a suitable alternative for a biokinetic model of deoxynivalenol (DON). IndusChemFate (ICF) was selected as a generic PBK model, which could be fit for purpose. Being suited for simulating multiple routes of exposure, ICF has particularly been used to relate the inhalation and dermal exposure of industrial chemicals to their urinary excretion. For the first time, the ICF model was adapted as a generic model for the human biomonitoring of mycotoxins, thereby extending its applicability domain. For this purpose, chemical-specific data for DON and its metabolites were collected directly from the literature (distribution and metabolism) or indirectly (absorption and excretion) by fitting the ICF model to previously described urinary excretion data. The obtained results indicate that this generic model can be used to model the urinary excretion of DON and its glucuronidated metabolites following dietary exposure to DON. Additionally, the present study establishes the basis for further development of the model to include an inhalation exposure route alongside the oral exposure route.
ISSN:2072-6651
2072-6651
DOI:10.3390/toxins15090569