Department of Biology, University of Ottawa, Ottawa, Ontario, Canada.
Toxicol Sci. 2013 Jul;134(1):92-102. doi: 10.1093/toxsci/kft100. Epub 2013 Apr 29.
Tris(1-chloro-2-propyl) phosphate (TCPP) and tris(1,3-dichloro-2-propyl) phosphate (TDCPP) are organic flame retardants detected in the environment and biota for which avian toxicological data are limited. In this study, domestic chicken eggs were injected with TCPP or TDCPP (maximum dose = 51,600 and 45,000ng/g egg, respectively) to determine dose-dependent effects on pipping success, development, hepatic messenger RNA (mRNA) expression levels of genes associated with xenobiotic metabolism and the thyroid hormone (TH) pathway, and TH levels following 20-22 days of incubation. Neither compound reduced pipping success; however, TCPP significantly delayed pipping at 9240 and 51,600ng/g and reduced tarsus length at 51,600ng/g. TDCPP exposure resulted in significant decreases in head plus bill length, embryo mass, and gallbladder size at 45,000ng/g and reduced plasma free T4 levels at 7640ng/g. Type I deiodinase, liver fatty acid-binding protein, and cytochrome P450 (CYP) 3A37 mRNA levels were significantly induced by TCPP, whereas TDCPP induced CYP3A37 and CYP2H1. Chemical analysis of egg contents at incubation days 0, 5, 11, 18, and 19 revealed that > 92% of the injected TCPP or TDCPP concentration was detectable up to day 5; however, < 1% was detected by day 19. The observed phenotypic responses to TCPP and TDCPP exposure may be associated with disruption of the TH axis, which is critical for normal growth and development in birds. The effects of TDCPP on the gallbladder indicate that the disturbance of lipid metabolism is a likely mechanism of toxicity.
磷酸三(1-氯-2-丙基)酯(TCPP)和磷酸三(1,3-二氯-2-丙基)酯(TDCPP)是环境和生物群中检测到的有机阻燃剂,其鸟类毒理学数据有限。在这项研究中,向家鸡蛋中注射 TCPP 或 TDCPP(最大剂量分别为 51600 和 45000ng/g 鸡蛋),以确定剂量依赖性对出雏成功率、发育、与外源性代谢和甲状腺激素(TH)途径相关的基因的肝信使 RNA(mRNA)表达水平以及孵化 20-22 天后的 TH 水平的影响。这两种化合物都没有降低出雏成功率;然而,TCPP 分别在 9240 和 51600ng/g 时显著延迟出雏,在 51600ng/g 时降低跗跖长度。TDCPP 暴露导致在 45000ng/g 时显著降低头加喙长、胚胎质量和胆囊大小,在 7640ng/g 时降低血浆游离 T4 水平。TCPP 显著诱导 I 型脱碘酶、肝脂肪酸结合蛋白和细胞色素 P450(CYP)3A37mRNA 水平,而 TDCPP 诱导 CYP3A37 和 CYP2H1。孵化第 0、5、11、18 和 19 天对鸡蛋内容物进行的化学分析表明,高达第 5 天,注射的 TCPP 或 TDCPP 浓度的>92%是可检测到的;然而,到第 19 天,<1%是可检测到的。对 TCPP 和 TDCPP 暴露的表型反应可能与 TH 轴的破坏有关,TH 轴对鸟类的正常生长和发育至关重要。TDCPP 对胆囊的影响表明,脂质代谢的干扰可能是其毒性的一种机制。