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大鼠体内多氯联苯的组织分布及半衰期与血清中4-羟基-2,3,3',4',5-五氯联苯水平

Tissue distribution and half-lives of individual polychlorinated biphenyls and serum levels of 4-hydroxy-2,3,3',4',5-pentachlorobiphenyl in the rat.

作者信息

Oberg Mattias, Sjödin Andreas, Casabona Helena, Nordgren Ingrid, Klasson-Wehler Eva, Håkansson Helen

机构信息

Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

出版信息

Toxicol Sci. 2002 Dec;70(2):171-82. doi: 10.1093/toxsci/70.2.171.

Abstract

This study was done to generate kinetic data on individual congeners of chlorinated biphenyls in the low dose range, which could be of value in the risk assessment procedure. Male Sprague-Dawley rats were given a single oral dose of a mixture of polychlorinated biphenyls (CBs) containing either CBs 105, 118, 138, 153, 156, 157, 170, and 180 (A-mix) or CBs 28, 52, 77, 87, and 101 (B-mix). Liver, serum, and adipose tissue were collected after 6 h up to 135 days, from rats given the A-mix, and after 6 h up to 4 days from rats given the B-mix. CB concentrations were measured in liver, serum, and adipose tissue. In addition, this study provides kinetic data of one of the major CB metabolites, 4-hydroxy-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107). The low doses used resulted in serum CB concentrations similar to human background serum concentrations. In the A-mix experiment all CBs show high initial liver and serum concentrations followed by redistribution into adipose tissue. Differences between congeners were correlated to molecular weight. High molecular weight correlated to lower uptake and slower redistribution. During dynamic steady-state the tissue concentrations decreased with a calculated first order rate between 54-129 days for halving the concentrations (half-life). Most of the decrease in concentration was explained by the growth-related increase of tissue masses in general and adipose tissue in particular. In the B-mix experiment, the concentrations of CBs in adipose tissue decreased with between 25 and 59% from day 1 to day 4. These results show that the B-mix congeners, given at low dose, have longer half-lives than previously reported in high dose studies. Partition coefficients between body compartments are reported and for the first time a high and congener specific liver-to-serum ratio of CB 77 is observed.

摘要

本研究旨在获取低剂量范围内多氯联苯各同系物的动力学数据,这些数据在风险评估过程中可能具有价值。给雄性斯普拉格 - 道利大鼠单次口服含有多氯联苯(CBs)的混合物,其中一种混合物包含CBs 105、118、138、153、156、157、170和180(A混合物),另一种包含CBs 28、52、77、87和101(B混合物)。在给A混合物的大鼠中,于6小时后至135天收集肝脏、血清和脂肪组织;在给B混合物的大鼠中,于6小时后至4天收集这些组织。测量肝脏、血清和脂肪组织中的CB浓度。此外,本研究还提供了主要CB代谢物之一4 - 羟基 - 2,3,3',4',5 - 五氯联苯(4 - OH - CB107)的动力学数据。所使用的低剂量导致血清CB浓度与人背景血清浓度相似。在A混合物实验中,所有CBs在肝脏和血清中的初始浓度都很高,随后重新分布到脂肪组织中。同系物之间的差异与分子量相关。高分子量与较低的摄取和较慢的重新分布相关。在动态稳态期间,组织浓度以计算得出的一级速率下降,浓度减半的时间(半衰期)在54 - 129天之间。浓度的大部分下降可归因于总体组织质量特别是脂肪组织质量与生长相关的增加。在B混合物实验中,从第1天到第4天,脂肪组织中CBs的浓度下降了25%至59%。这些结果表明,低剂量给予的B混合物同系物的半衰期比先前高剂量研究中报道的更长。报告了身体各部分之间的分配系数,并且首次观察到CB 77具有高且同系物特异性的肝 - 血清比率。

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