Tributyl phosphate (TBP), an organophosphate ester (OPE), is heavily used as a solvent in chemical industries, a plasticizer, and to extract radioactive molecules. Thus, widespread uses of TBP in industrialized countries led to the release of TBP and its metabolites, dibutyl phosphate (DBP) and monobutyl phosphate (MBP), in the environment and were detected in human samples. Accumulating these OPEs over time in humans and aquatic animals may develop toxicological effects. The reports also say TBP passes through the mother-fetal transmission route and may affect embryonic development. However, the impact of TBP and its metabolites on vertebrate development has been poorly studied. Ex-utero development, high fecundity, and optical transparency make the zebrafish a preferred model for toxicological evaluation. Thus, we aim to explore the toxic effects of TBP and its metabolites on aquatic animals using zebrafish as a model organism. Embryos in the chorion were incubated in 10–60 µM test chemicals from 6 to 48 h post fertilization (hpf), and analyzed the adverse effects on embryos. Our study found that 10–20 µM TBP inhibits neural growth, resulting in decreased spontaneous movement frequency and locomotive behavior without altering the overall embryonic growth and muscle functions. In contrast, DBP-treated embryos showed increased spontaneous movement frequency without changing the motor neuron growth and locomotive behavior. Further, in higher concentrations, TBP is teratogenic, and DBP is lethal to the embryos. Altogether, we found that TBP inhibits neurogenesis and motor behavior; however, its metabolite DBP is neuroexcitatory in zebrafish embryos.

中文翻译：

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磷酸三丁酯抑制斑马鱼胚胎发育过程中的神经发生和运动功能


磷酸三丁酯 （TBP） 是一种有机磷酸酯 （OPE），在化学工业中被广泛用作溶剂、增塑剂和提取放射性分子。因此，TBP 在工业化国家的广泛使用导致 TBP 及其代谢物磷酸二丁酯 （DBP） 和磷酸单丁酯 （MBP） 在环境中释放，并在人类样本中检测到。随着时间的推移，这些 OPE 在人类和水生动物体内积累可能会产生毒理学效应。报告还说，TBP 通过母胎传播途径传播，可能会影响胚胎发育。然而，TBP 及其代谢物对脊椎动物发育的影响研究不足。子宫外发育、高繁殖力和光学透明度使斑马鱼成为毒理学评估的首选模型。因此，我们旨在以斑马鱼为模式生物探索 TBP 及其代谢物对水生动物的毒性作用。将绒毛膜中的胚胎在受精后 6 至 48 小时 （hpf） 在 10-60 μM 测试化学品中孵育，并分析对胚胎的不利影响。我们的研究发现，10-20 μM TBP 抑制神经生长，导致自发运动频率和运动行为降低，而不会改变整体胚胎生长和肌肉功能。相比之下，DBP 处理的胚胎表现出自发运动频率增加，而没有改变运动神经元生长和运动行为。此外，在较高浓度下，TBP 具有致畸性，而 DBP 对胚胎是致命的。总而言之，我们发现 TBP 抑制神经发生和运动行为;然而，其代谢物 DBP 在斑马鱼胚胎中具有神经兴奋性。