A comprehensive evaluation of the endocrine-disrupting effects of emerging organophosphate esters

The ubiquitous presence of organophosphate esters (OPEs) in the environment has prompted growing concerns about their potential health risks, particularly their endocrine-disrupting effects. This study comprehensively evaluated the endocrine-disrupting properties of six emerging OPEs: five aryl-OPEs...

Full description

Saved in:
Bibliographic Details
Main Authors: Quan Zhang, Liuqing Yang, Huiyun Wang, Chengwang Wu, Rui Cao, Meirong Zhao, Guanyong Su, Cui Wang
Format: Article
Language:English
Published: Elsevier 2024-11-01
Series:Environment International
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0160412024007062
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850130042995081216
author Quan Zhang
Liuqing Yang
Huiyun Wang
Chengwang Wu
Rui Cao
Meirong Zhao
Guanyong Su
Cui Wang
author_facet Quan Zhang
Liuqing Yang
Huiyun Wang
Chengwang Wu
Rui Cao
Meirong Zhao
Guanyong Su
Cui Wang
author_sort Quan Zhang
collection DOAJ
description The ubiquitous presence of organophosphate esters (OPEs) in the environment has prompted growing concerns about their potential health risks, particularly their endocrine-disrupting effects. This study comprehensively evaluated the endocrine-disrupting properties of six emerging OPEs: five aryl-OPEs (2-ethylhexyl diphenyl phosphate (EHDPP), tris (2-biphenylyl) phosphate (TBPP), resorcinol bis (diphenyl phosphate) (RDP), 4-hydroxyphenyl diphenyl phosphate (para-OH-TPHP), and 3-hydroxyphenyl diphenyl phosphate (meta-OH-TPHP) and one alkyl-OPE, triallyl phosphate (TAP). Our findings revealed that all tested aryl-OPEs exhibited antagonistic effects on one or more hormone receptors. Importantly, para-OH-TPHP demonstrated the most potent antagonistic activity, inhibiting estrogen receptor α (ERα), thyroid hormone receptor β (TRβ), glucocorticoid receptor (GR), and mineralocorticoid receptor (MR) with the concentration of test compounds showing 20 % relative inhibitory concentration (RIC20) value below 10−6 mol/L (M). RDP antagonized ERα and cortical receptors (GR and MR), TBPP affected TRβ and GR, while EHDPP and meta-OH-TPHP targeted MR. Regarding steroidogenesis, para-OH-TPHP significantly inhibited genes for estrogen (cyp19) and cortisol synthesis (cyp11b2), and along with meta-OH-TPHP, EHDPP, TAP, and RDP downregulated cyp11a1, a rate-limiting enzyme in hormone synthesis. All compounds caused malformations and swimming abnormalities in zebrafish embryos/larvae at concentrations of 10−7 M or higher, with para-OH-TPHP showing nearly 50 % peak induction. Furthermore, the six compounds tested influenced genes associated with the hypothalamic-pituitary–gonadal (HPG) axis in both zebrafish larvae and adult female zebrafish, in addition to affecting the reproductive behavior of zebrafish. A weighted scoring system was employed to rank the endocrine-disrupting potency of the OPEs, with para-OH-TPHP exhibiting the highest risk, followed by EHDPP, RDP, TBPP, meta-OH-TPHP, and TAP. Collectively, our results highlight the significant endocrine-disrupting effects of emerging OPEs, underscoring the urgent need for further research to assess their potential health implications.
format Article
id doaj-art-fa87bf216c144d74b039e1a8e5fa9bf6
institution OA Journals
issn 0160-4120
language English
publishDate 2024-11-01
publisher Elsevier
record_format Article
series Environment International
spelling doaj-art-fa87bf216c144d74b039e1a8e5fa9bf62025-08-20T02:32:48ZengElsevierEnvironment International0160-41202024-11-0119310912010.1016/j.envint.2024.109120A comprehensive evaluation of the endocrine-disrupting effects of emerging organophosphate estersQuan Zhang0Liuqing Yang1Huiyun Wang2Chengwang Wu3Rui Cao4Meirong Zhao5Guanyong Su6Cui Wang7College of Environment, Zhejiang University of Technology, Hangzhou, Zhejiang 310032, ChinaCollege of Environment, Zhejiang University of Technology, Hangzhou, Zhejiang 310032, ChinaCollege of Environment, Zhejiang University of Technology, Hangzhou, Zhejiang 310032, ChinaCollege of Environment, Zhejiang University of Technology, Hangzhou, Zhejiang 310032, ChinaCollege of Environment, Zhejiang University of Technology, Hangzhou, Zhejiang 310032, ChinaCollege of Environment, Zhejiang University of Technology, Hangzhou, Zhejiang 310032, ChinaJiangsu Key Laboratory of Chemical Pollution Control and Resources Reuse, School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing 210094, ChinaSchool of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China; Corresponding author.The ubiquitous presence of organophosphate esters (OPEs) in the environment has prompted growing concerns about their potential health risks, particularly their endocrine-disrupting effects. This study comprehensively evaluated the endocrine-disrupting properties of six emerging OPEs: five aryl-OPEs (2-ethylhexyl diphenyl phosphate (EHDPP), tris (2-biphenylyl) phosphate (TBPP), resorcinol bis (diphenyl phosphate) (RDP), 4-hydroxyphenyl diphenyl phosphate (para-OH-TPHP), and 3-hydroxyphenyl diphenyl phosphate (meta-OH-TPHP) and one alkyl-OPE, triallyl phosphate (TAP). Our findings revealed that all tested aryl-OPEs exhibited antagonistic effects on one or more hormone receptors. Importantly, para-OH-TPHP demonstrated the most potent antagonistic activity, inhibiting estrogen receptor α (ERα), thyroid hormone receptor β (TRβ), glucocorticoid receptor (GR), and mineralocorticoid receptor (MR) with the concentration of test compounds showing 20 % relative inhibitory concentration (RIC20) value below 10−6 mol/L (M). RDP antagonized ERα and cortical receptors (GR and MR), TBPP affected TRβ and GR, while EHDPP and meta-OH-TPHP targeted MR. Regarding steroidogenesis, para-OH-TPHP significantly inhibited genes for estrogen (cyp19) and cortisol synthesis (cyp11b2), and along with meta-OH-TPHP, EHDPP, TAP, and RDP downregulated cyp11a1, a rate-limiting enzyme in hormone synthesis. All compounds caused malformations and swimming abnormalities in zebrafish embryos/larvae at concentrations of 10−7 M or higher, with para-OH-TPHP showing nearly 50 % peak induction. Furthermore, the six compounds tested influenced genes associated with the hypothalamic-pituitary–gonadal (HPG) axis in both zebrafish larvae and adult female zebrafish, in addition to affecting the reproductive behavior of zebrafish. A weighted scoring system was employed to rank the endocrine-disrupting potency of the OPEs, with para-OH-TPHP exhibiting the highest risk, followed by EHDPP, RDP, TBPP, meta-OH-TPHP, and TAP. Collectively, our results highlight the significant endocrine-disrupting effects of emerging OPEs, underscoring the urgent need for further research to assess their potential health implications.http://www.sciencedirect.com/science/article/pii/S0160412024007062Emerging organophosphate estersHormone nuclear receptorsSteroidogenesisDevelopment toxicity
spellingShingle Quan Zhang
Liuqing Yang
Huiyun Wang
Chengwang Wu
Rui Cao
Meirong Zhao
Guanyong Su
Cui Wang
A comprehensive evaluation of the endocrine-disrupting effects of emerging organophosphate esters
Environment International
Emerging organophosphate esters
Hormone nuclear receptors
Steroidogenesis
Development toxicity
title A comprehensive evaluation of the endocrine-disrupting effects of emerging organophosphate esters
title_full A comprehensive evaluation of the endocrine-disrupting effects of emerging organophosphate esters
title_fullStr A comprehensive evaluation of the endocrine-disrupting effects of emerging organophosphate esters
title_full_unstemmed A comprehensive evaluation of the endocrine-disrupting effects of emerging organophosphate esters
title_short A comprehensive evaluation of the endocrine-disrupting effects of emerging organophosphate esters
title_sort comprehensive evaluation of the endocrine disrupting effects of emerging organophosphate esters
topic Emerging organophosphate esters
Hormone nuclear receptors
Steroidogenesis
Development toxicity
url http://www.sciencedirect.com/science/article/pii/S0160412024007062
work_keys_str_mv AT quanzhang acomprehensiveevaluationoftheendocrinedisruptingeffectsofemergingorganophosphateesters
AT liuqingyang acomprehensiveevaluationoftheendocrinedisruptingeffectsofemergingorganophosphateesters
AT huiyunwang acomprehensiveevaluationoftheendocrinedisruptingeffectsofemergingorganophosphateesters
AT chengwangwu acomprehensiveevaluationoftheendocrinedisruptingeffectsofemergingorganophosphateesters
AT ruicao acomprehensiveevaluationoftheendocrinedisruptingeffectsofemergingorganophosphateesters
AT meirongzhao acomprehensiveevaluationoftheendocrinedisruptingeffectsofemergingorganophosphateesters
AT guanyongsu acomprehensiveevaluationoftheendocrinedisruptingeffectsofemergingorganophosphateesters
AT cuiwang acomprehensiveevaluationoftheendocrinedisruptingeffectsofemergingorganophosphateesters
AT quanzhang comprehensiveevaluationoftheendocrinedisruptingeffectsofemergingorganophosphateesters
AT liuqingyang comprehensiveevaluationoftheendocrinedisruptingeffectsofemergingorganophosphateesters
AT huiyunwang comprehensiveevaluationoftheendocrinedisruptingeffectsofemergingorganophosphateesters
AT chengwangwu comprehensiveevaluationoftheendocrinedisruptingeffectsofemergingorganophosphateesters
AT ruicao comprehensiveevaluationoftheendocrinedisruptingeffectsofemergingorganophosphateesters
AT meirongzhao comprehensiveevaluationoftheendocrinedisruptingeffectsofemergingorganophosphateesters
AT guanyongsu comprehensiveevaluationoftheendocrinedisruptingeffectsofemergingorganophosphateesters
AT cuiwang comprehensiveevaluationoftheendocrinedisruptingeffectsofemergingorganophosphateesters