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体内吸入的(14)C 标记 PCB11 及其代谢物的命运。

The fate of inhaled (14)C-labeled PCB11 and its metabolites in vivo.

机构信息

Department of Occupational and Environmental Health, University of Iowa, Iowa City, IA 52242, USA.

出版信息

Environ Int. 2014 Feb;63:92-100. doi: 10.1016/j.envint.2013.10.017. Epub 2013 Nov 22.

DOI:10.1016/j.envint.2013.10.017
PMID:24275706
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3950335/
Abstract

BACKGROUND

The production ban of polychlorinated biphenyl (PCB) technical mixtures has left the erroneous impression that PCBs exist only as legacy pollutants. Some lower-chlorinated PCBs are still being produced and contaminate both indoor and ambient air.

OBJECTIVES

To inform PCB risk assessment, we characterized lung uptake, distribution, metabolism and excretion of PCB11 as a signature compound for these airborne non-legacy PCBs.

METHODS

After delivering [(14)C]PCB11 to the lungs of male rats, radioactivity in 34 major tissues and 5 digestive matter compartments was measured at 12, 25, 50, 100, 200 and 720min postexposure, during which time the excreta and exhaled air were also collected. [(14)C]PCB11 and metabolites in lung, liver, blood, digestive matter, urine, feces, and adipose tissues were extracted separately to establish the metabolic profile of the disposition.

RESULTS

[(14)C]PCB11 was distributed rapidly to all tissues after 99.8% pulmonary uptake and quickly underwent extensive metabolism. The major tissue deposition of [(14)C]PCB11 and metabolites translocated from liver, blood and muscle to skin and adipose tissue 200min postexposure, while over 50% of administered dose was discharged via urine and feces within 12h. Elimination of the [(14)C]PCB11 and metabolites consisted of an initial fast phase (t½=9-33min) and a slower clearance phase to low concentrations. Phase II metabolites dominated in liver blood and excreta after 25min postexposure.

CONCLUSIONS

This study shows that PCB11 is completely absorbed after inhalation exposure and is rapidly eliminated from most tissues. Phase II metabolites dominated with a slower elimination rate than the PCB11 or phase I metabolites and thus can best serve as urine biomarkers of exposure.

摘要

背景

多氯联苯 (PCB) 技术混合物的生产禁令给人留下了这样一种错误印象,即 PCB 仅作为遗留污染物存在。一些低氯代 PCB 仍在生产,并污染室内和环境空气。

目的

为了告知 PCB 风险评估,我们对 PCB11 作为这些空气传播非遗留 PCB 的特征化合物进行了肺部摄取、分布、代谢和排泄的特征描述。

方法

将 [(14)C]PCB11 输送到雄性大鼠肺部后,在暴露后 12、25、50、100、200 和 720 分钟时测量 34 个主要组织和 5 个消化物隔室中的放射性,在此期间还收集了排泄物和呼出的空气。分别从肺部、肝脏、血液、消化物、尿液、粪便和脂肪组织中提取 [(14)C]PCB11 和代谢物,以建立其处置的代谢谱。

结果

[(14)C]PCB11 在 99.8%肺摄取后迅速分布到所有组织,并迅速进行广泛代谢。[(14)C]PCB11 及其从肝脏、血液和肌肉转移到皮肤和脂肪组织的主要组织沉积在暴露后 200 分钟,而超过 50%的给药剂量在 12 小时内通过尿液和粪便排出。[(14)C]PCB11 和代谢物的消除由初始快速相(t½=9-33 分钟)和较慢的清除相组成,直至低浓度。暴露后 25 分钟,Ⅱ相代谢物在肝脏、血液和排泄物中占主导地位。

结论

这项研究表明,PCB11 经吸入暴露后完全被吸收,并从大多数组织中迅速消除。Ⅱ相代谢物以比 PCB11 或Ⅰ相代谢物更慢的消除率为主,因此可以作为暴露的尿液生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d063/3950335/12e0504fd920/nihms-538744-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d063/3950335/0e643ab8875d/nihms-538744-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d063/3950335/eb30c4d53d6d/nihms-538744-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d063/3950335/30eb355d64b7/nihms-538744-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d063/3950335/12e0504fd920/nihms-538744-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d063/3950335/0e643ab8875d/nihms-538744-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d063/3950335/eb30c4d53d6d/nihms-538744-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d063/3950335/30eb355d64b7/nihms-538744-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d063/3950335/12e0504fd920/nihms-538744-f0004.jpg

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