A comprehensive evaluation of the endocrine-disrupting effects of emerging organophosphate esters
Quan Zhang, Liuqing Yang, Hui‐Yun Wang, Chengwang Wu, Rui Cao, Meirong Zhao, Guanyong Su, Cui Wang
Abstract
• All tested OPEs, except TAP, exhibited as antagonists against hormone receptors. • para -OH-TPHP significantly inhibited the mRNA involved in steroidogenesis. • All tested OPEs exerted development toxicity to zebrafish embryos/larval. • All tested OPEs impacted genes in the HPG axis of zebrafish larvae and adult females. • para -OH-TPHP exerts the most potent of endocrine disruption. 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 (RIC 20 ) 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.