Organophosphate ester flame retardants have antiandrogenic potential and affect other endocrine related endpoints in vitro and in silico
| Autor: | Eva Bay Wedebye, Morlin Möller, Hanna Katarina Lilith Johansson, Anne Marie Vinggaard, Anna Kjerstine Rosenmai, Sofia Boeg Winge, Nikolai Georgiev Nikolov, Johan Lundqvist |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Environmental Engineering medicine.drug_class Health Toxicology and Mutagenesis In silico 0208 environmental biotechnology 02 engineering and technology 010501 environmental sciences Pharmacology 01 natural sciences chemistry.chemical_compound medicine Environmental Chemistry Endocrine system Humans Computer Simulation 0105 earth and related environmental sciences Flame Retardants biology CYP3A4 Estrogen receptor binding Organophosphate Public Health Environmental and Occupational Health Infant Newborn Esters Estrogens General Medicine General Chemistry Aryl hydrocarbon receptor Pollution Organophosphates 020801 environmental engineering Androgen receptor chemistry Estrogen biology.protein |
| Zdroj: | Chemosphere. 263 |
| ISSN: | 1879-1298 |
| Popis: | Organophosphate ester flame retardants (OPFRs) are used to prevent ignition and spreading of fire. They are present in various human matrices suggesting adult, fetal, and neonate exposure. Endocrine related effects have been observed in vivo, but information at the molecular level is lacking for some OPFRs. Also, a better understanding of potential contribution from chemical substructures is needed. The aim of this study was to screen OPFRs for endocrine disruptive potential in vitro and in silico. We selected eleven substances to represent some OPFRs with 1) little information on endocrine activity and others to represent 2) varied chemical substructures. We used in vitro assays for androgen receptor (AR), aryl hydrocarbon receptor (AhR), and Nrf2 activity, effects on steroidogenesis, and transthyretin (TTR) binding, as well as in silico models covering estrogen, thyroid, and CYP3A4 induction related endpoints. Ten OPFRs affected AR and AhR activity, seven affected TTR binding, and five affected 17β-estradiol levels. Several substances had IC50-values below 10 μM and exhibited efficacious effects. These included TPHP, CDP, TMPP, TIPPP, and EHDPP for AR antagonism, suggesting that the degree of arylation and the size of the substance can play a role for the activity. Chlorinated OPFRs had low/no effect on TTR binding. No clear trend was observed for AhR and steroidogenesis, but all arylated OPFRs were predicted to have alert for estrogen receptor binding in an in silico model with metabolism simulator included. Collectively, our data suggest that OPFRs have endocrine disruptive potential warranting further studies to enable human risk assessment. |
| Databáze: | OpenAIRE |
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