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磷酸三(2-丁氧基乙基)酯和磷酸三乙酯会改变鸡胚的胚胎发育、肝脏mRNA表达、甲状腺激素水平以及循环胆汁酸浓度。

Tris(2-butoxyethyl)phosphate and triethyl phosphate alter embryonic development, hepatic mRNA expression, thyroid hormone levels, and circulating bile acid concentrations in chicken embryos.

作者信息

Egloff Caroline, Crump Doug, Porter Emily, Williams Kim L, Letcher Robert J, Gauthier Lewis T, Kennedy Sean W

机构信息

National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3, Canada.

National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3, Canada.

出版信息

Toxicol Appl Pharmacol. 2014 Sep 15;279(3):303-310. doi: 10.1016/j.taap.2014.06.024. Epub 2014 Jul 3.

DOI:10.1016/j.taap.2014.06.024
PMID:24998971
Abstract

The organophosphate flame retardants tris(2-butoxyethyl) phosphate (TBOEP) and triethyl phosphate (TEP) are used in a wide range of applications to suppress or delay the ignition and spread of fire. Both compounds have been detected in the environment and TBOEP was recently measured in free-living avian species. In this study, TBOEP and TEP were injected into the air cell of chicken embryos at concentrations ranging from 0 to 45,400 ng/g and 0 to 241,500 ng/g egg, respectively. Pipping success, development, hepatic mRNA expression of 9 target genes, thyroid hormone levels, and circulating bile acid concentrations were determined. Exposure to the highest doses of TBOEP and TEP resulted in negligible detection of the parent compounds in embryonic contents at pipping indicating their complete metabolic degradation. TBOEP exposure had limited effects on chicken embryos, with the exception of hepatic CYP3A37 mRNA induction. TEP exposure decreased pipping success to 68%, altered growth, increased liver somatic index (LSI) and plasma bile acids, and modulated genes associated with xenobiotic and lipid metabolism and the thyroid hormone pathway. Plasma thyroxine levels were decreased at all TEP doses, including an environmentally-relevant concentration (8 ng/g), and gallbladder hypotrophy was evident at ≥ 43,200 ng/g. Tarsus length and circulating thyroxine concentration emerged as potential phenotypic anchors for the modulation of transthyretin mRNA. The increase in plasma bile acids and LSI, gallbladder hypotrophy, and discoloration of liver tissue represented potential phenotypic outcomes associated with modulation of hepatic genes involved with xenobiotic and lipid metabolism.

摘要

有机磷酸酯类阻燃剂磷酸三(2-丁氧基乙基)酯(TBOEP)和磷酸三乙酯(TEP)被广泛应用于抑制或延缓火灾的点燃和蔓延。这两种化合物均已在环境中被检测到,最近还在自由生活的鸟类物种中检测到了TBOEP。在本研究中,分别以0至45400 ng/g和0至241500 ng/g鸡蛋的浓度将TBOEP和TEP注入鸡胚的气室。测定了啄壳成功率、发育情况、9个靶基因的肝脏mRNA表达、甲状腺激素水平和循环胆汁酸浓度。暴露于最高剂量的TBOEP和TEP后,在啄壳时胚胎内容物中母体化合物的检测量可忽略不计,表明它们已完全代谢降解。TBOEP暴露对鸡胚的影响有限,除了肝脏CYP3A37 mRNA的诱导。TEP暴露使啄壳成功率降至68%,改变了生长情况,增加了肝脏体指数(LSI)和血浆胆汁酸,并调节了与异生物代谢、脂质代谢和甲状腺激素途径相关的基因。所有TEP剂量下,包括环境相关浓度(8 ng/g),血浆甲状腺素水平均降低,且在≥43200 ng/g时胆囊萎缩明显。跗骨长度和循环甲状腺素浓度成为调节转甲状腺素蛋白mRNA的潜在表型指标。血浆胆汁酸和LSI的增加、胆囊萎缩以及肝组织变色代表了与参与异生物和脂质代谢的肝脏基因调节相关的潜在表型结果。

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