PDF(Pubmed)
Abstract：
A common flame-retardant and plasticizer, triphenyl phosphate (TPhP) is an aryl phosphate ester found in many aquatic environments at nM concentrations. Yet, most studies interrogating its toxicity have used µM concentrations. In this study, we used the model organism zebrafish (Danio rerio) to uncover the developmental impact of nM exposures to TPhP at the phenotypic and molecular levels. At concentrations of 1.5-15 nM (0.5 µg/L-5 µg/L), chronically dosed 5dpf larvae were shorter in length and had pericardial edema phenotypes that had been previously reported for exposures in the µM range. Cardiotoxicity was observed but did not present as cardiac looping defects as previously reported for µM concentrations. The RXR pathway does not seem to be involved at nM concentrations, but the tbx5a transcription factor cascade including natriuretic peptides (nppa and nppb) and bone morphogenetic protein 4 (bmp4) were dysregulated and could be contributing to the cardiac phenotypes. We also demonstrate that TPhP is a weak pro-oxidant, as it increases the oxidative stress response within hours of exposure. Overall, our data indicate that TPhP can affect animal development at environmentally relevant concentrations and its mode of action involves multiple pathways.
摘要：
常见的阻燃剂和增塑剂，磷酸三苯酯（TPhP）是在许多水生环境中以nM浓度发现的芳基磷酸酯。然而，大多数询问其毒性的研究都使用μM浓度。在这项研究中,我们使用模型生物斑马鱼（Daniorerio）在表型和分子水平上揭示了nM暴露于TPhP的发育影响。浓度为1.5-15nM（0.5µg/L-5µg/L），长期给药的5dpf幼虫的长度较短，并且具有先前报道的在µM范围内暴露的心包水肿表型。观察到心脏毒性，但不存在先前报道的μM浓度的心脏循环缺陷。RXR途径似乎在nM浓度下不涉及，但是包括利钠肽（nppa和nppb）和骨形态发生蛋白4（bmp4）在内的tbx5a转录因子级联调节异常，可能导致心脏表型。我们还证明了TPhP是一种弱氧化剂，因为它在暴露后数小时内增加了氧化应激反应。总的来说,我们的数据表明,TPhP在环境相关浓度下可影响动物发育,其作用方式涉及多种途径.
