Nallani Gopinath C, Edziyie Regina E, Paulos Peter M, Venables Barney J, Constantine Lisa A, Huggett Duane B
Institute of Applied Sciences, Department of Biological Sciences, University of North Texas, Denton, Texas, USA.
Pfizer Global Research and Development, Groton, Connecticut, USA.
Environ Toxicol Chem. 2016 Mar;35(3):593-603. doi: 10.1002/etc.3244. Epub 2016 Feb 9.
The present study examined the bioconcentration of 2 basic pharmaceuticals: verapamil (a calcium channel blocker) and clozapine (an antipsychotic compound) in 2 fresh water fishes, fathead minnow and channel catfish. In 4 separate bioconcentration factor (BCF) experiments (2 chemicals × 1 exposure concentration × 2 fishes), fathead minnow and channel catfish were exposed to 190 μg/L and 419 μg/L of verapamil (500 μg/L nominal) or 28.5 μg/L and 40 μg/L of clozapine (50 μg/L nominal), respectively. Bioconcentration factor experiments with fathead consisted of 28 d uptake and 14 d depuration, whereas tests conducted on catfish involved a minimized test design, with 7 d each of uptake and depuration. Fish (n = 4-5) were sampled during exposure and depuration to collect different tissues: muscle, liver, gills, kidneys, heart (verapamil tests only), brain (clozapine tests only), and blood plasma (catfish tests only). Verapamil and clozapine concentrations in various tissues of fathead and catfish were analyzed using liquid chromatography-mass spectrometry. In general, higher accumulation rates of the test compounds were observed in tissues with higher perfusion rates. Accumulation was also high in tissues relevant to pharmacological targets in mammals (i.e. heart in verapamil test and brain in the clozapine test). Tissue-specific BCFs (wet wt basis) for verapamil and clozapine ranged from 0.7 to 75 and from 31 to 1226, respectively. Tissue-specific concentration data were used to examine tissue-blood partition coefficients.
本研究检测了两种碱性药物(维拉帕米,一种钙通道阻滞剂;氯氮平,一种抗精神病化合物)在两种淡水鱼(黑头呆鱼和斑点叉尾鮰)中的生物富集情况。在4个独立的生物富集因子(BCF)实验(2种化学物质×1个暴露浓度×2种鱼)中,黑头呆鱼和斑点叉尾鮰分别暴露于190μg/L和419μg/L的维拉帕米(标称浓度500μg/L)或28.5μg/L和40μg/L的氯氮平(标称浓度50μg/L)。对黑头呆鱼进行的生物富集因子实验包括28天的摄取期和14天的净化期,而对斑点叉尾鮰进行的实验采用了简化的实验设计,摄取期和净化期均为7天。在暴露期和净化期对鱼(n = 4 - 5)进行采样,以收集不同组织:肌肉、肝脏、鳃、肾脏、心脏(仅维拉帕米实验)、脑(仅氯氮平实验)和血浆(仅斑点叉尾鮰实验)。使用液相色谱 - 质谱法分析黑头呆鱼和斑点叉尾鮰各组织中维拉帕米和氯氮平的浓度。一般来说,在灌注率较高的组织中观察到受试化合物的积累率更高。在与哺乳动物药理学靶点相关的组织中(即维拉帕米实验中的心脏和氯氮平实验中的脑)积累也很高。维拉帕米和氯氮平的组织特异性生物富集因子(以湿重计)分别为0.7至75和31至1226。组织特异性浓度数据用于检测组织 - 血液分配系数。