The development of a pregnancy PBPK Model for Bisphenol A and its evaluation with the available biomonitoring data
Open accessAbstract
Recent studies suggest universal fetal exposure to Bisphenol A (BPA) and its association with the adverse birth outcomes. Estimation of the fetal plasma BPA concentration from the maternal plasma BPA would be highly useful to predict its associated risk to this specific population. The objective of current work is to develop a pregnancy-physiologically based pharmacokinetic (P-PBPK) model to predict the toxicokinetic profile of BPA in the fetus during gestational growth, and to evaluate the developed model using biomonitoring data obtained from different pregnancy cohort studies. To achieve this objective, first, the adult PBPK model was developed and validated with the human BPA toxicokinetic data. This validated human PBPK model was extended to develop a P-PBPK model, which included the physiological changes during pregnancy and the fetus sub-model. The developed model would be able to predict the BPA pharmacokinetics (PKs) in both mother and fetus. Transplacental BPA kinetics parameters for this study were taken from the previous pregnant mice study. Both oral and dermal exposure routes were included into the model to simulate total BPA internal exposure. The impact of conjugation and deconjugation of the BPA and its metabolites on fetal PKs was investigated. The developed P-PBPK model was evaluated against the observed BPA concentrations in cord blood, fetus liver and amniotic fluid considering maternal blood concentration as an exposure source. A range of maternal exposu…
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Sharma et al. developed a p-PBPK model for bisphenol A where the fetal compartment also encompassed organs like brain, liver, and kidney.
“Sharma et al. developed a p-PBPK model for bisphenol A where the fetal compartment also encompassed organs like brain, liver, and kidney (Sharma et al., 2018).”
From Pregnancy-related maternal physiological adaptations and fetal chemical exposure (2023) · cites this paper as Sharma et al., 2018
The Sharma model predicted higher mid-gestation exposure in the fetal liver, in agreement with some observational studies.
“The model predicted higher mid-gestation exposure in the fetal liver in agreement with some observational studies.”
From Pregnancy-related maternal physiological adaptations and fetal chemical exposure (2023) · cites this paper as Sharma et al., 2018
Validation of models on rapidly-metabolized compounds will remain challenging due to differing lifestyle variables just prior to sampling in biomonitoring studies and functional genetic variations in metabolizing enzymes in different populations.
“Although the model by Sharma showed good potential, the authors acknowledged that validation of models on rapidly-metabolized com pounds will remain challenging due not only to differing lifestyle vari ables just prior sampling in biomonitoring studies, but also functional genetic variations in metabolizing enzymes in different populations.”
From Pregnancy-related maternal physiological adaptations and fetal chemical exposure (2023) · cites this paper as Sharma et al., 2018
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Pregnancy-related maternal physiological adaptations and fetal chemical exposure
Vinnars, M.-T., Bixo, M., & Damdimopoulou, P. (2023) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2023.112064 · Cited by 32 · see citing works
- Authors
- Sharma, R. P., Schuhmacher, M., & Kumar, V.
- Affiliations
- Universitat Rovira i Virgili (ES)
- Corresponding author
- Kumar, Vikas
- Venue
- Science of The Total Environment
- Publisher
- Elsevier BV
- Published
- 2018-05
- Volume
- 624
- Pages
- 55-68
- ISSN
- 0048-9697 (ISSN-L)
- OpenAlex
- W2772476494
- Cited by
- 68
- References
- 5
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 3 · 2023: 6 · 2022: 10 · 2021: 10 · 2020: 12 · 2019: 11 · 2018: 8
- FWCI
- 4.56
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- The Science of The Total Environment (publishedVersion)
- PubMed (publishedVersion)
- Rovira & Virgili repository (submittedVersion, cc-by)
- Funders
- Universitat Rovira i Virgili
- Horizon 2020 Framework Programme (633172)
- Seventh Framework Programme (603946)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Pesticide Exposure and Toxicity
- Keywords
- bisphenol A, pregnancy, physiologically based pharmacokinetic modeling, prenatal exposure, transplacental transfer, umbilical cord blood, amniotic fluid, fetal liver, dermal exposure, oral exposure, critical windows of exposure, adverse birth outcomes
- MeSH terms
- Bisphenol A Compounds, Animals, Benzhydryl Compounds, Environmental Monitoring, Female, Humans, Models, Biological, Phenols, Pregnancy, Maternal Exposure, Mice
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