Quinete Natalia, Esser André, Kraus Thomas, Schettgen Thomas
Institute for Occupational and Social Medicine, Medical Faculty, RWTH Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany.
Institute for Occupational and Social Medicine, Medical Faculty, RWTH Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany.
Toxicol Lett. 2017 Jul 5;276:100-107. doi: 10.1016/j.toxlet.2017.05.025. Epub 2017 May 25.
Polychlorinated biphenyls (PCBs) are suspected of carcinogenic, neurotoxic and immunotoxic effects in animals and humans. Although background levels of PCBs have been slowly decreased after their ban, they are still among the most persistent and ubiquitous pollutants in the environment, remaining the subject of great concern. PCB 28 is a trichlorinated PCB found in high concentrations not only in human plasma but also in indoor air in Europe, yet little is known about its metabolic pathway and potential metabolites in humans. The present study aims to elucidate the kinetics of metabolite formation and elimination by analyzing four hydroxylated PCBs (OH-PCBs) in human plasma as potential metabolites of the PCB 28 congener. For this purpose, the study was conducted in plasma samples of highly PCB-exposed individuals (N=268), collected from 2010 to 2014 as a representation of a real case scenario with longitudinal data. OH-PCBs have been predicted, synthesized in the course of this study and further identified and quantitated in human plasma. This is the first time that previously unknown PCB 28 metabolites have been measured in human plasma and half-lives have been estimated for PCB metabolites, which could then provide further understanding in the toxicological consequences of exposure to PCBs in humans.
多氯联苯(PCBs)被怀疑对动物和人类具有致癌、神经毒性和免疫毒性作用。尽管在多氯联苯被禁止使用后,其背景水平已在缓慢下降,但它们仍是环境中最持久且分布最广的污染物之一,仍然备受关注。PCB 28是一种三氯代多氯联苯,不仅在人体血浆中,而且在欧洲的室内空气中都有高浓度存在,然而人们对其在人体内的代谢途径和潜在代谢产物知之甚少。本研究旨在通过分析人体血浆中的四种羟基化多氯联苯(OH-PCBs)作为PCB 28同系物的潜在代谢产物,来阐明代谢产物形成和消除的动力学。为此,该研究在2010年至2014年收集的高暴露于多氯联苯个体的血浆样本(N = 268)中进行,这些样本代表了具有纵向数据的真实案例。在本研究过程中预测、合成了OH-PCBs,并在人体血浆中进一步进行了鉴定和定量。这是首次在人体血浆中测量到先前未知的PCB 28代谢产物,并估算了PCB代谢产物的半衰期,这进而可以为了解人体接触多氯联苯的毒理学后果提供进一步的依据。