生物信息学
芳香烃受体
内分泌干扰物
化学
有机磷
雌激素受体
内分泌系统
雄激素受体
体外毒理学
药理学
体外
生物
生物化学
激素
转录因子
前列腺癌
基因
农学
乳腺癌
杀虫剂
癌症
遗传学
作者
Anna Kjerstine Rosenmai,Sofia Boeg Winge,Morlin Möller,Johan Lundqvist,Eva Bay Wedebye,Nikolai Georgiev Nikolov,Hanna Johansson,Anne Marie Vinggaard
出处
期刊:Chemosphere
[Elsevier]
日期:2021-01-01
卷期号:263: 127703-127703
被引量:43
标识
DOI:10.1016/j.chemosphere.2020.127703
摘要
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.
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