Linking Transthyretin-Binding Chemicals and Free Thyroid Hormones: In Vitro to In Vivo Extrapolation Based on a Competitive Binding Model.
Environ Sci Technol
; 57(25): 9130-9139, 2023 06 27.
Article
em En
| MEDLINE
| ID: mdl-37261382
ABSTRACT
Large numbers of pollutants competitively inhibit the binding between thyroid hormones and transthyretin (TTR) in vitro. However, the impact of this unintended binding on free thyroid hormones in vivo has not yet been characterized. Herein, we established a quantitative in vitro to in vivo extrapolation (QIVIVE) method based on a competitive binding model to quantify the effect of TTR-binding chemicals on free thyroid hormones in human blood. Twenty-five TTR-binding chemicals including 6 hydroxyl polybromodiphenyl ethers (OH-PDBEs), 6 hydroxyl polychlorobiphenyls (OH-PCBs), 4 halogenphenols, 5 per- and polyfluorinated substances (PFASs), and 4 phenols were selected for investigation. Incorporating the in vitro binding parameters and human exposure data, the QIVIVE model could well predict the in vivo effect on free thyroid hormones. Co-exposure to twenty-five typical TTR-binding chemicals resulted in median increases of 0.080 and 0.060% in circulating levels of free thyroxine (FT4) and free triiodothyronine (FT3) in the general population. Individuals with occupational exposure to TTR-binding chemicals suffered 1.88-32.2% increases in free thyroid hormone levels. This study provides a quantitative tool to evaluate the thyroid-disrupting risks of TTR-binding chemicals and proposes a new framework for assessing the in vivo effects of chemical exposures on endogenous molecules.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Hormônios Tireóideos
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Pré-Albumina
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Bifenilos Policlorados
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Poluentes Ambientais
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Environ Sci Technol
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China