IVIVE-PBPK based new approach methodology for addressing early life toxicity induced by bisphenol A

Autor segons l'article: Ni, Mengmei; Deepika, Deepika; Li, Xiaomeng; Xiong, Wei; Zhang, Lishi; Chen, Jinyao; Kumar, Vikas

Departament: Enginyeria Química

Autor/s de la URV: , Deepika / Kumar, Vikas

Paraules clau: Toxicogenomics; Toxicity tests; Pregnancy; Phenols; Pbpk; Neurotoxicity; Ivive; In-vivo extrapolation; Humans; Human embryonic stem cells; Food safety; Female; Embryotoxicity; Bisphenol a; Benzhydryl compounds; water; vitro; toxicogenomics; stem-cell test; risk-assessment; pbpk; neurotoxicity; ivive; integration; human embryonic stem cells; exposure; embryotoxicity; dosimetry; analogs

Resum: Bisphenol A (BPA) is a known endocrine disruptor mimicking natural estrogens with the potential to affect human health, especially during prenatal and postnatal exposure at or below current acceptable daily intake levels. Different adverse effects of BPA are still under investigation, and multiple mechanisms of action remain unexplored. This may be one of the reasons for the continuously changing tolerable daily intake (TDI) of BPA with the emergence of new adverse health effects over time. In addition, translational modelling through in vitro-in vivo extrapolation (IVIVE) can act as prerequisite bridge for translating in-vitro finding into human risk assessment. The objective of this study was to conduct in-vitro experiments and utilize an IVIVE-pregnancy physiologically based pharmacokinetic (P-PBPK) modeling to investigate developmental neurotoxicity and embryotoxicity in humans. The data obtained from human embryonic stem cells-based assays (study conducted between October 2020-2021) were used for the IVIVE-P-PBPK models to obtain the human equivalent doses (HEDs) which were further extrapolated to reference doses (RfDs). The results showed that simulated mean RfDs (μg/kg/day) derived from the HSD3B1 and NFATC2 gene of embryotoxicity and neurodevelopmental toxicity tests, respectively, were 4.94 and 5.18. The simulated RfDs were close to the temporary-tolerable daily intake (t-TDI) recommended by European Food Safety Authority (EFSA) in 2015 (t-TDI: 4 μg/kg·bw) and higher than the TDI of 2023 (0.2 ng/kg·bw). In conclusion, in-vitro toxicogenomics dose-response data combined with PBPK modeling can become a promising alternativenew approach methodology (NAM) to support decision-making in chemical risk assessment. Based on the simulated RfDs derived from this NAM, the t-TDI set by EFSA in 2015 may be considered a safe exposure limit for mothers and fetuses at the current BPA intake levels in Chinese mothers. This study provided an animal-free new strategy for NAMs based risk assessment by combining toxicogenomics and computational toxicology.Copyright © 2023. Published by Elsevier Inc.

Àrees temàtiques: 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

Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/

Adreça de correu electrònic de l'autor: vikas.kumar@urv.cat; deepika@iispv.cat; deepika@iispv.cat

Data d'alta del registre: 2025-03-03

Versió de l'article dipositat: info:eu-repo/semantics/acceptedVersion

Enllaç font original: https://www.sciencedirect.com/science/article/pii/S0013935123021473

URL Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/

Referència a l'article segons font original: Environmental Research. 240 (Pt 1): 117343-117343

Referència de l'ítem segons les normes APA: Ni, Mengmei; Deepika, Deepika; Li, Xiaomeng; Xiong, Wei; Zhang, Lishi; Chen, Jinyao; Kumar, Vikas (2024). IVIVE-PBPK based new approach methodology for addressing early life toxicity induced by bisphenol A. Environmental Research, 240(Pt 1), 117343-117343. DOI: 10.1016/j.envres.2023.117343

DOI de l'article: 10.1016/j.envres.2023.117343

Entitat: Universitat Rovira i Virgili

Any de publicació de la revista: 2024

Tipus de publicació: Journal Publications