Articles producció científica> Enginyeria Química

Influence of the uncertainty in the validation of PBPK models: A case-study for PFOS and PFOA

  • Datos identificativos

    Identificador: imarina:6388634
    Autores:
    Fabrega, FrancescNadal, MartiSchuhmacher, MartaDomingo, Jose LKumar, Vikas
    Resumen:
    © 2016 Elsevier Inc. Physiologically-based pharmacokinetic (PBPK) models are mathematical representations of the human body aimed at describing the time course distribution of chemicals in human tissues. Since parameterization of PBPK models is based on empirical estimation and experimental data, simulation results may have high degree of uncertainty. As a consequence, the reliability of model validation is highly affected. In this study, the parametric uncertainty associated with PBPK models developed for perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) were analyzed and the different validation approaches were discussed for a case-study in Tarragona County (NE of Spain). Physicochemical parameters and dietary intake of PFOS and PFOA were estimated from previous investigations performed in Tarragona County. A sensitivity analysis (SA) was performed to understand the degree of influence of input parameters on the final outcomes. The uncertainty of the PBPK models' outcome was assessed by propagating the parametric uncertainty using the Latin Hypercube Sampling (LHS) technique. The elimination constants (Tm and Kt) as well as the Free fraction and the Intake, were the most influential parameters according to the SA results, being up to 83% for PFOS and 99.9% for PFOA. The validation of the PBPK model, which was performed using different approaches, showed clear discrepancies in the visual validation when compared with the statistical analysis.
  • Otros:

    Autor según el artículo: Fabrega, Francesc; Nadal, Marti; Schuhmacher, Marta; Domingo, Jose L; Kumar, Vikas
    Departamento: Enginyeria Química Ciències Mèdiques Bàsiques
    Autor/es de la URV: Domingo Roig, José Luis / FABREGA BONADONA, FRANCESC / Kumar, Vikas / Nadal Lomas, Martí / Schuhmacher Ansuategui, Marta
    Palabras clave: Uncertainty analysis Physiologically based pharmacokinetic (pbpk) model Perfluorooctanoic acid (pfoa) Perfluorooctane sulfonic acid (pfos) Model validation physiologically based pharmacokinetic (pbpk) model perfluorooctanoic acid (pfoa) perfluorooctane sulfonic acid (pfos) model validation
    Resumen: © 2016 Elsevier Inc. Physiologically-based pharmacokinetic (PBPK) models are mathematical representations of the human body aimed at describing the time course distribution of chemicals in human tissues. Since parameterization of PBPK models is based on empirical estimation and experimental data, simulation results may have high degree of uncertainty. As a consequence, the reliability of model validation is highly affected. In this study, the parametric uncertainty associated with PBPK models developed for perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) were analyzed and the different validation approaches were discussed for a case-study in Tarragona County (NE of Spain). Physicochemical parameters and dietary intake of PFOS and PFOA were estimated from previous investigations performed in Tarragona County. A sensitivity analysis (SA) was performed to understand the degree of influence of input parameters on the final outcomes. The uncertainty of the PBPK models' outcome was assessed by propagating the parametric uncertainty using the Latin Hypercube Sampling (LHS) technique. The elimination constants (Tm and Kt) as well as the Free fraction and the Intake, were the most influential parameters according to the SA results, being up to 83% for PFOS and 99.9% for PFOA. The validation of the PBPK model, which was performed using different approaches, showed clear discrepancies in the visual validation when compared with the statistical analysis.
    Áreas temáticas: Toxicology Saúde coletiva Química Pharmacology & pharmacy Odontología Medicine, legal Medicine (miscellaneous) Medicina ii Medicina i Interdisciplinar Farmacia Ciências biológicas ii Ciências biológicas i Ciências ambientais Ciência de alimentos Biotecnología Biodiversidade
    Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/
    ISSN: 02732300
    Direcció de correo del autor: vikas.kumar@urv.cat joseluis.domingo@urv.cat marti.nadal@urv.cat marta.schuhmacher@urv.cat
    Identificador del autor: 0000-0002-9795-5967 0000-0001-6647-9470 0000-0002-0217-4827 0000-0003-4381-2490
    Fecha de alta del registro: 2024-10-12
    Versión del articulo depositado: info:eu-repo/semantics/acceptedVersion
    Enlace a la fuente original: https://www.sciencedirect.com/science/article/abs/pii/S027323001630054X?via%3Dihub
    URL Documento de licencia: https://repositori.urv.cat/ca/proteccio-de-dades/
    Referencia al articulo segun fuente origial: Regulatory Toxicology And Pharmacology. 77 230-239
    Referencia de l'ítem segons les normes APA: Fabrega, Francesc; Nadal, Marti; Schuhmacher, Marta; Domingo, Jose L; Kumar, Vikas (2016). Influence of the uncertainty in the validation of PBPK models: A case-study for PFOS and PFOA. Regulatory Toxicology And Pharmacology, 77(), 230-239. DOI: 10.1016/j.yrtph.2016.03.009
    DOI del artículo: 10.1016/j.yrtph.2016.03.009
    Entidad: Universitat Rovira i Virgili
    Año de publicación de la revista: 2016
    Tipo de publicación: Journal Publications
  • Palabras clave:

    Medicine (Miscellaneous),Medicine, Legal,Pharmacology & Pharmacy,Toxicology
    Uncertainty analysis
    Physiologically based pharmacokinetic (pbpk) model
    Perfluorooctanoic acid (pfoa)
    Perfluorooctane sulfonic acid (pfos)
    Model validation
    physiologically based pharmacokinetic (pbpk) model
    perfluorooctanoic acid (pfoa)
    perfluorooctane sulfonic acid (pfos)
    model validation
    Toxicology
    Saúde coletiva
    Química
    Pharmacology & pharmacy
    Odontología
    Medicine, legal
    Medicine (miscellaneous)
    Medicina ii
    Medicina i
    Interdisciplinar
    Farmacia
    Ciências biológicas ii
    Ciências biológicas i
    Ciências ambientais
    Ciência de alimentos
    Biotecnología
    Biodiversidade
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