Articles producció científica> Enginyeria Química

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

  • Identification data

    Identifier: imarina:6388634
    Authors:
    Fabrega, FrancescNadal, MartiSchuhmacher, MartaDomingo, Jose LKumar, Vikas
    Abstract:
    © 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.
  • Others:

    Author, as appears in the article.: Fabrega, Francesc; Nadal, Marti; Schuhmacher, Marta; Domingo, Jose L; Kumar, Vikas
    Department: Enginyeria Química Ciències Mèdiques Bàsiques
    URV's Author/s: Domingo Roig, José Luis / FABREGA BONADONA, FRANCESC / Kumar, Vikas / Nadal Lomas, Martí / Schuhmacher Ansuategui, Marta
    Keywords: 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
    Abstract: © 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.
    Thematic Areas: 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
    licence for use: https://creativecommons.org/licenses/by/3.0/es/
    ISSN: 02732300
    Author's mail: vikas.kumar@urv.cat joseluis.domingo@urv.cat marti.nadal@urv.cat marta.schuhmacher@urv.cat
    Author identifier: 0000-0002-9795-5967 0000-0001-6647-9470 0000-0002-0217-4827 0000-0003-4381-2490
    Record's date: 2024-10-12
    Papper version: info:eu-repo/semantics/acceptedVersion
    Link to the original source: https://www.sciencedirect.com/science/article/abs/pii/S027323001630054X?via%3Dihub
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Papper original source: Regulatory Toxicology And Pharmacology. 77 230-239
    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
    Article's DOI: 10.1016/j.yrtph.2016.03.009
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2016
    Publication Type: Journal Publications
  • Keywords:

    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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