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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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Autores principales: Notenboom, Sylvia, Hoogenveen, Rudolf T., Zeilmaker, Marco J., Van den Brand, Annick D., Assunção, Ricardo, Mengelers, Marcel J. B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10535232/
https://www.ncbi.nlm.nih.gov/pubmed/37755995
http://dx.doi.org/10.3390/toxins15090569
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author Notenboom, Sylvia
Hoogenveen, Rudolf T.
Zeilmaker, Marco J.
Van den Brand, Annick D.
Assunção, Ricardo
Mengelers, Marcel J. B.
author_facet Notenboom, Sylvia
Hoogenveen, Rudolf T.
Zeilmaker, Marco J.
Van den Brand, Annick D.
Assunção, Ricardo
Mengelers, Marcel J. B.
author_sort Notenboom, Sylvia
collection PubMed
description 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.
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spelling pubmed-105352322023-09-29 Development of a Generic PBK Model for Human Biomonitoring with an Application to Deoxynivalenol Notenboom, Sylvia Hoogenveen, Rudolf T. Zeilmaker, Marco J. Van den Brand, Annick D. Assunção, Ricardo Mengelers, Marcel J. B. Toxins (Basel) Article 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. MDPI 2023-09-13 /pmc/articles/PMC10535232/ /pubmed/37755995 http://dx.doi.org/10.3390/toxins15090569 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Notenboom, Sylvia
Hoogenveen, Rudolf T.
Zeilmaker, Marco J.
Van den Brand, Annick D.
Assunção, Ricardo
Mengelers, Marcel J. B.
Development of a Generic PBK Model for Human Biomonitoring with an Application to Deoxynivalenol
title Development of a Generic PBK Model for Human Biomonitoring with an Application to Deoxynivalenol
title_full Development of a Generic PBK Model for Human Biomonitoring with an Application to Deoxynivalenol
title_fullStr Development of a Generic PBK Model for Human Biomonitoring with an Application to Deoxynivalenol
title_full_unstemmed Development of a Generic PBK Model for Human Biomonitoring with an Application to Deoxynivalenol
title_short Development of a Generic PBK Model for Human Biomonitoring with an Application to Deoxynivalenol
title_sort development of a generic pbk model for human biomonitoring with an application to deoxynivalenol
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10535232/
https://www.ncbi.nlm.nih.gov/pubmed/37755995
http://dx.doi.org/10.3390/toxins15090569
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