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虹鳟幼鱼(Oncorhynchus mykiss)中顺式和反式脱氯菊酯异构体的异构体特异性生物累积参数及潜在体内肝脏代谢物研究

Examination of isomer specific bioaccumulation parameters and potential in vivo hepatic metabolites of syn- and anti-Dechlorane Plus isomers in juvenile rainbow trout (Oncorhynchus mykiss).

作者信息

Tomy Gregg T, Thomas Caden R, Zidane Thane M, Murison Kathryn E, Pleskach Kerri, Hare Jonathon, Arsenault Gilles, Marvin Chris H, Sverko Ed

机构信息

Department of Fisheries and Oceans, Arctic Aquatic Research Division, Winnipeg, MB R3T 2N6, Canada.

出版信息

Environ Sci Technol. 2008 Aug 1;42(15):5562-7. doi: 10.1021/es800220y.

DOI:10.1021/es800220y
PMID:18754476
Abstract

Juvenile rainbow trout (Oncorhynchus mykiss) were exposed in the laboratory to elevated doses of syn- and anti-isomers of Dechlorane Plus (DP) via their diet for 49 days (uptake phase), followed by 112 days of untreated food (depuration phase) to examine bioaccumulation parameters and possible metabolic products. Three groups of 60 fish were used in the study. Two groups were exposed separately to food fortified with known concentrations of syn- (0.79 +/- 0.03 microg/g, lipid weight) and anti-DP (1.17 +/- 0.12 microg/g, lipid weight) while a third control group was fed unfortified food. Neither isomer reached steady-state after 49 days of exposure. Only the syn-isomer accumulated linearly in the fish (whole-body minus liver) during the dosing phase with a calculated uptake rate constant of 0.045 +/- 0.005 (arithmetic mean +/- 1 x standard error) nmoles per day. A similar uptake rate was also observed for this isomer in the liver. The elimination of both isomers from the whole fish (minus liver) obeyed first order depuration kinetics (syn-: r2 = 0.6427, p < 0.001, anti-: r2 = 0.5350, p < 0.005) with calculated half-lives (t1/2) of 53.3 +/- 13.1 (syn-) and 30.4 +/- 5.7 (anti-) days. Elimination of the isomers from the liver was difficult to interpret because of suspected enterohepatic circulation and redistribution of the isomers in the liver during clearance from other tissues. The biomagnification factor (BMF, determined in whole fish minus liver) of the syn-isomer (5.2) was greater than the anti-isomer (1.9) suggesting that the former isomer is more bioavailable. A suite of metabolites were screened for in the liver including dechlorinated, hydroxylated, methoxylated and methyl sulfone degradates. Even with the purposely high dose used in the uptake phase, none of these degradates could be detected in the extracts. This suggests that if metabolites of DP are detected in fish from aquatic food webs their presence is likely not from in vivo biotransformation of the parent compound.

摘要

在实验室中,通过饮食让幼年虹鳟鱼(Oncorhynchus mykiss)接触高剂量的十氯酮(DP)顺式和反式异构体49天(摄取阶段),随后喂食112天未添加该物质的食物(净化阶段),以研究生物累积参数和可能的代谢产物。该研究使用了三组,每组60条鱼。两组分别接触添加了已知浓度顺式DP(0.79±0.03微克/克,脂质重量)和反式DP(1.17±0.12微克/克,脂质重量)的食物,而第三组对照组喂食未添加的食物。暴露49天后,两种异构体均未达到稳态。在给药阶段,只有顺式异构体在鱼体(全身减去肝脏)中呈线性累积,计算得出的摄取速率常数为每天0.045±0.005(算术平均值±1×标准误差)纳摩尔。在肝脏中也观察到该异构体有类似的摄取速率。两种异构体从整条鱼(减去肝脏)中的消除均符合一级净化动力学(顺式:r2 = 0.6427,p < 0.001;反式:r2 = 0.5350,p < 0.005),计算得出的半衰期(t1/2)分别为53.3±13.1(顺式)和30.4±5.7(反式)天。由于怀疑存在肝肠循环以及在从其他组织清除过程中异构体在肝脏中的重新分布,所以很难解释异构体从肝脏中的消除情况。顺式异构体(5.2)的生物放大因子(在整条鱼减去肝脏中测定)大于反式异构体(1.9),这表明前一种异构体的生物可利用性更高。在肝脏中筛选了一系列代谢产物,包括脱氯、羟基化、甲氧基化和甲基砜降解产物。即使在摄取阶段故意使用高剂量,提取物中也未检测到这些降解产物。这表明,如果在水生食物网的鱼类中检测到DP的代谢产物,其存在可能并非来自母体化合物的体内生物转化。

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