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Unravelling sex-specific BPA toxicokinetics in children using a pediatric PBPK model

  • Datos identificativos

    Identificador: imarina:9282210
    Autores:
    Deepika, DeepikaSharma, Raju PrasadSchuhmacher, MartaSakhi, Amrit KaurThomsen, CathrineChatzi, LedaVafeiadi, MarinaQuentin, JoaneSlama, RemyGrazuleviciene, ReginaAndrusaityte, SandraWaiblinger, DagmarWright, JohnYang, Tiffany CUrquiza, JoseVrijheid, MartineCasas, MaribelDomingo, Jose LKumar, Vikas
    Resumen:
    Bisphenol A (BPA) is a widely known endocrine disruptor (ED) found in many children's products such as toys, feeding utensils, and teething rings. Recent epidemiology association studies have shown postnatal BPA exposure resulted in developing various diseases such as diabetes, obesity, and neurodegeneration, etc., later in their lives. However, little is known about its sex-specific metabolism and consequently internal exposure. The aim of this study was to develop a sex-specific pediatric physiologically based pharmacokinetic model (PBPK) for BPA to compare their toxicokinetic differences. First, the published adult PBPK model was re-validated, and then this model was extended by interpolation to incorporate pediatric sex specific physiological and biochemical parameters. We used both the classical body weight and ontogeny-based scaling approach to interpolate the metabolic process. Then, the pharmacokinetic attributes of the models using the two-scaling approach mentioned above were compared with adult model. Further, a sex-specific PBPK model with an ontogeny scaling approach was preferred to evaluate the pharmacokinetic differences. Moreover, this model was used to reconstruct the BPA exposure from two cohorts (Helix and PBAT Cohort) from 7 EU countries. The half-life of BPA was found to be almost the same in boys and girls at the same exposure levels. Our model estimated BPA children's exposure to be about 1500 times higher than the tolerable daily intake (TDI) recently set by European Food Safety Authority (EFSA) i.e., 0.04 ng/kg BW/day. The model demonstrated feasibility of extending the adult PBPK to sex-specific pediatric, thus investigate a gender-specific health risk assessment.
  • Otros:

    Autor según el artículo: Deepika, Deepika; Sharma, Raju Prasad; Schuhmacher, Marta; Sakhi, Amrit Kaur; Thomsen, Cathrine; Chatzi, Leda; Vafeiadi, Marina; Quentin, Joane; Slama, Remy; Grazuleviciene, Regina; Andrusaityte, Sandra; Waiblinger, Dagmar; Wright, John; Yang, Tiffany C; Urquiza, Jose; Vrijheid, Martine; Casas, Maribel; Domingo, Jose L; Kumar, Vikas
    Departamento: Ciències Mèdiques Bàsiques Enginyeria Química
    Autor/es de la URV: , Deepika / Domingo Roig, José Luis / Kumar, Vikas / Schuhmacher Ansuategui, Marta
    Palabras clave: Sex-specific risk Pharmacokinetic Pediatric pbpk Endocrine disruptor Children cohort Bisphenol-a concentrations Bisphenol a values sex -specific risk protein-binding pharmacokinetics pharmacokinetic mother gender-differences exposure excretion endocrine disruptor children cohort bisphenol a
    Resumen: Bisphenol A (BPA) is a widely known endocrine disruptor (ED) found in many children's products such as toys, feeding utensils, and teething rings. Recent epidemiology association studies have shown postnatal BPA exposure resulted in developing various diseases such as diabetes, obesity, and neurodegeneration, etc., later in their lives. However, little is known about its sex-specific metabolism and consequently internal exposure. The aim of this study was to develop a sex-specific pediatric physiologically based pharmacokinetic model (PBPK) for BPA to compare their toxicokinetic differences. First, the published adult PBPK model was re-validated, and then this model was extended by interpolation to incorporate pediatric sex specific physiological and biochemical parameters. We used both the classical body weight and ontogeny-based scaling approach to interpolate the metabolic process. Then, the pharmacokinetic attributes of the models using the two-scaling approach mentioned above were compared with adult model. Further, a sex-specific PBPK model with an ontogeny scaling approach was preferred to evaluate the pharmacokinetic differences. Moreover, this model was used to reconstruct the BPA exposure from two cohorts (Helix and PBAT Cohort) from 7 EU countries. The half-life of BPA was found to be almost the same in boys and girls at the same exposure levels. Our model estimated BPA children's exposure to be about 1500 times higher than the tolerable daily intake (TDI) recently set by European Food Safety Authority (EFSA) i.e., 0.04 ng/kg BW/day. The model demonstrated feasibility of extending the adult PBPK to sex-specific pediatric, thus investigate a gender-specific health risk assessment.
    Áreas temáticas: Zootecnia / recursos pesqueiros Saúde coletiva Química Public, environmental & occupational health Public health, environmental and occupational health Psicología Planejamento urbano e regional / demografia Odontología Medicina iii Medicina ii Medicina i Materiais Interdisciplinar Geociências General medicine General environmental science Farmacia Environmental sciences Environmental science (miscellaneous) Environmental science (all) Ensino Engenharias iii Engenharias ii Engenharias i Enfermagem Educação física Direito Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências ambientais Ciências agrárias i Ciência de alimentos Biotecnología Biodiversidade Biochemistry Astronomia / física
    Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/
    Direcció de correo del autor: vikas.kumar@urv.cat deepika@urv.cat deepika@urv.cat joseluis.domingo@urv.cat marta.schuhmacher@urv.cat
    Identificador del autor: 0000-0002-9795-5967 0000-0001-6647-9470 0000-0003-4381-2490
    Fecha de alta del registro: 2024-10-12
    Versión del articulo depositado: info:eu-repo/semantics/publishedVersion
    URL Documento de licencia: https://repositori.urv.cat/ca/proteccio-de-dades/
    Referencia al articulo segun fuente origial: Environmental Research. 215 (Pt 1): 114074-
    Referencia de l'ítem segons les normes APA: Deepika, Deepika; Sharma, Raju Prasad; Schuhmacher, Marta; Sakhi, Amrit Kaur; Thomsen, Cathrine; Chatzi, Leda; Vafeiadi, Marina; Quentin, Joane; Slama (2022). Unravelling sex-specific BPA toxicokinetics in children using a pediatric PBPK model. Environmental Research, 215(Pt 1), 114074-. DOI: 10.1016/j.envres.2022.114074
    Entidad: Universitat Rovira i Virgili
    Año de publicación de la revista: 2022
    Tipo de publicación: Journal Publications
  • Palabras clave:

    Biochemistry,Environmental Science (Miscellaneous),Environmental Sciences,Public, Environmental & Occupational Health
    Sex-specific risk
    Pharmacokinetic
    Pediatric pbpk
    Endocrine disruptor
    Children cohort
    Bisphenol-a concentrations
    Bisphenol a
    values
    sex -specific risk
    protein-binding
    pharmacokinetics
    pharmacokinetic
    mother
    gender-differences
    exposure
    excretion
    endocrine disruptor
    children cohort
    bisphenol a
    Zootecnia / recursos pesqueiros
    Saúde coletiva
    Química
    Public, environmental & occupational health
    Public health, environmental and occupational health
    Psicología
    Planejamento urbano e regional / demografia
    Odontología
    Medicina iii
    Medicina ii
    Medicina i
    Materiais
    Interdisciplinar
    Geociências
    General medicine
    General environmental science
    Farmacia
    Environmental sciences
    Environmental science (miscellaneous)
    Environmental science (all)
    Ensino
    Engenharias iii
    Engenharias ii
    Engenharias i
    Enfermagem
    Educação física
    Direito
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
    Ciências ambientais
    Ciências agrárias i
    Ciência de alimentos
    Biotecnología
    Biodiversidade
    Biochemistry
    Astronomia / física
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