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

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• dc.contributor.author Deepika, Deepika
• dc.contributor.author Sharma, Raju Prasad
• dc.contributor.author Schuhmacher, Marta
• dc.contributor.author Sakhi, Amrit Kaur
• dc.contributor.author Thomsen, Cathrine
• dc.contributor.author Chatzi, Leda
• dc.contributor.author Vafeiadi, Marina, 1983-
• dc.contributor.author Quentin, Joane
• dc.contributor.author Slama, Rémy
• dc.contributor.author Gražulevičienė, Regina
• dc.contributor.author Andrušaitytė, Sandra
• dc.contributor.author Waiblinger, Dagmar
• dc.contributor.author Wright, John
• dc.contributor.author Yang, Tiffany C.
• dc.contributor.author Urquiza, José M.
• dc.contributor.author Vrijheid, Martine
• dc.contributor.author Casas Sanahuja, Maribel
• dc.contributor.author Domingo, José L.
• dc.contributor.author Kumar, Vikas
• dc.date.accessioned 2022-11-30T07:44:04Z
• dc.date.available 2022-11-30T07:44:04Z
• dc.date.issued 2022
• dc.description.abstract 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.
• dc.description.sponsorship This study was financially supported by Marie Skłodowska-Curie “Neurosome Project” under the grant agreement No. 766251, the European Community funded H2020 HBM4EU project under Grant Agreements no. 733032, and the Instituto de Salud Carlos III (PI17/01194), and the European Community's Seventh Framework Programme (FP7/2007–206) under grant agreement no 308333 (HELIX project). Maribel Casas holds a Miguel Servet fellowship (CP16/00128) funded by Instituto de Salud Carlos III and co-funded by European Social Fund “Investing in your future”. We acknowledge support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019–2023” Program (2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. This publication reflects only the authors' views. The Community and other funding organizations are not liable for any use made of the information contained therein. Born in Bradford is only possible because of the enthusiasm and commitment of the children and parents in Born in Bradford. We are grateful to all participants, health professionals and researchers who have made Born in Bradford happen. BiB receives core infrastructure funding from the Wellcome Trust (WT101597MA) and a joint grant from the UK Medical Research Council (MRC) and Economic and Social Science Research Council (ESRC) (MR/N024397/1). This study has received support from European Research Council under the European Union's Seventh Framework Programme (FP7/2007–2013)/ERC grant agreement no 669545 and National Institute for Health Research Applied Research Collaboration Yorkshire and Humber (NIHR200166).
• dc.format.mimetype application/pdf
• dc.identifier.citation Deepika D, Sharma RP, Schuhmacher M, Sakhi AK, Thomsen C, Chatzi L, Vafeiadi M, Quentin J, Slama R, Grazuleviciene R, Andrušaitytė S, Waiblinger D, Wright J, Yang TC, Urquiza J, Vrijheid M, Casas M, Domingo JL, Kumar V. Unravelling sex-specific BPA toxicokinetics in children using a pediatric PBPK model. Environ Res. 2022 Dec;215(Pt 1):114074. DOI: 10.1016/j.envres.2022.114074
• dc.identifier.doi http://dx.doi.org/10.1016/j.envres.2022.114074
• dc.identifier.issn 0013-9351
• dc.identifier.uri http://hdl.handle.net/10230/55045
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof Environ Res. 2022 Dec;215(Pt 1):114074
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/766251
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/733032
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/308333
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/669545
• dc.rights © 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Bisphenol A
• dc.subject.keyword Children cohort
• dc.subject.keyword Endocrine disruptor
• dc.subject.keyword Pediatric PBPK
• dc.subject.keyword Pharmacokinetic
• dc.subject.keyword Sex-specific risk
• dc.title Unravelling sex-specific BPA toxicokinetics in children using a pediatric PBPK model
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion