Although high concentrations of 2-ethylhexyl diphenyl phosphate (EHDPP) have been detected in wild fish, its reproductive toxicity in fish remains unclear. In this study, we for the first time observed that EHDPP elicited androgen receptor (AR) antagonistic activity with a 50% inhibitory concentration of 37.5 μM. 2-Ethyl-5-hydroxyhexyl diphenyl phosphate was proved to be the dominant metabolite of EHDPP in Japanese medaka and elicited 3.1-fold stronger AR antagonistic activity than that of EHDPP. Medaka larvae (0-day post hatching) were exposed to EHDPP for 100 days, and intersex was observed in males from all exposure groups with significantly increased incidence (13.5–48.6%). 17β-E₂ was promoted at 104 ng/L, and androgens were suppressed at 434 ng/L, which account for the intersex incidence in the high-exposure groups but do not explain the significant incidence of intersex in the 29.9 ng/L exposure group. The AR antagonistic activity of EHDPP and its metabolites must therefore play a key role in intersex incidence. EHDPP also significantly (p < 0.05) repressed reproductive behaviors of males in the 434 ng/L group and decreased fertility in high-exposure groups compared with the control. All the adverse outcomes were observed under environmentally relevant concentrations, implying that EHDPP poses an ecological risk for wild fish populations.

中文翻译：

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2-乙基己基二苯基磷酸酯及其羟基化代谢物具有抗雄激素作用，可导致雄性日本Med（Oryzias latipes）繁殖不良。

尽管在野生鱼类中检测到高浓度的2-乙基己基二苯基磷酸酯（EHDPP），但其在鱼类中的生殖毒性仍不清楚。在这项研究中，我们首次观察到EHDPP以37.5μM的50％抑制浓度引起雄激素受体（AR）拮抗活性。已证明2-乙基-5-羟基己基磷酸二苯酯是日本高中EHDPP的主要代谢产物，并具有比EHDPP增强3.1倍的AR拮抗活性。将Medaka幼虫（孵化后0天）暴露于EHDPP中100天，并且在所有暴露组的男性中均发现了性交，发病率显着增加（13.5–48.6％）。17β-E ₂雌激素在104 ng / L时被促进，雄激素在434 ng / L时被抑制，这解释了高暴露组中性交的发生率，但不能解释29.9 ng / L暴露组中性交的显着发生率。因此，EHDPP及其代谢产物的AR拮抗活性必须在双性恋发病率中发挥关键作用。与对照组相比，EHDPP还显着（p <0.05）抑制了434 ng / L组男性的生殖行为，高暴露组的生育力下降。在与环境有关的浓度下观察到所有不利结果，这表明EHDPP对野生鱼类种群构成了生态风险。