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人类体内六氯苯的代谢:高暴露人群血清水平与尿液代谢物之间的关联。

Metabolism of hexachlorobenzene in humans: association between serum levels and urinary metabolites in a highly exposed population.

作者信息

To-Figueras J, Sala M, Otero R, Barrot C, Santiago-Silva M, Rodamilans M, Herrero C, Grimalt J, Sunyer J

机构信息

Toxicology Unit, Hospital Clinic, Facultat de Medicina, Universitat de Barcelona, Spain.

出版信息

Environ Health Perspect. 1997 Jan;105(1):78-83. doi: 10.1289/ehp.9710578.

DOI:10.1289/ehp.9710578
PMID:9074885
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1469858/
Abstract

Serum and urine from 100 subjects of a general population highly exposed to airborne hexachlorobenzene (HCB) were analyzed to obtain new insights into the metabolism of this ubiquitous compound. HCB was detected in all serum samples with concentrations ranging between 1.1 and 953 ng/ml. The major known metabolites of HCB were investigated in urine collected over 24 hr. Pentachlorophenol (PCP) was detected in all urines with values ranging between 0.58 and 13.9 micrograms excreted in 24 hr [mean +/- standard deviation (SD), 2.52 +/- 2.05; geometric mean, 2.05]. A sulfur derivative that, after hydrolysis, yielded pentachlorobenzenethiol (PCBT) could also be identified and quantified in all the urines with values ranging between 0.18 and 84.0 micrograms of PCBT excreted in 24 hr (mean +/- SD, 3.47 +/- 10.8; geometric mean, 1.39). The sulfur derivative assessed as PCBT appeared to be the main metabolite, with urinary concentrations surpassing those of PCP in the subjects with higher HCB accumulation (HCB in serum > 32 ng/ml). PCBT concentration in urine collected over 24 hr showed a very strong association with HCB concentration in serum; the association was stronger in males than in females. An increase of 1 ng/ml of HCB in serum led to an increase of 2.12 micrograms of PCBT excreted in urine collected over 24 hr in males (95% CI, 1.82-2.44) and to an increase of 0.67 microgram of PCBT in females (CI, 0.33-1.09). A weaker association was found between PCP in urine and HCB in serum, which was only statistically significant in males (an increase of 1 ng/ml of HCB in serum led to an increase of 0.63 microgram of PCP excreted in urine collected over 24 hr; (CI, 0.34-0.95). These results show that the formation of the cysteine conjugate is a quantitatively more important metabolic pathway in humans than the formation of PCP. Moreover, the association found suggests that PCBT is a good urinary marker of HCB internal dose and glutathione-mediated metabolism.

摘要

对100名长期暴露于空气中六氯苯(HCB)的普通人群的血清和尿液进行了分析,以获取有关这种普遍存在化合物代谢的新见解。在所有血清样本中均检测到HCB,浓度范围为1.1至953 ng/ml。对收集的24小时尿液中的HCB主要已知代谢物进行了研究。在所有尿液中均检测到五氯苯酚(PCP),24小时排泄量在0.58至13.9微克之间[均值±标准差(SD),2.52±2.05;几何均值,2.05]。还可以在所有尿液中鉴定并定量一种硫衍生物,水解后产生五氯苯硫酚(PCBT),24小时内PCBT排泄量在0.18至84.0微克之间(均值±SD,3.47±10.8;几何均值,1.39)。以PCBT评估的硫衍生物似乎是主要代谢物,在HCB蓄积量较高(血清中HCB>32 ng/ml)的受试者中,尿液浓度超过PCP。24小时收集的尿液中PCBT浓度与血清中HCB浓度显示出非常强的相关性;男性的相关性比女性更强。血清中HCB每增加1 ng/ml,男性24小时收集尿液中PCBT排泄量增加2.12微克(95%置信区间,1.82 - 2.44),女性增加0.67微克(置信区间,0.33 - 1.09)。尿液中PCP与血清中HCB之间的相关性较弱,仅在男性中具有统计学意义(血清中HCB每增加1 ng/ml,24小时收集尿液中PCP排泄量增加0.63微克;(置信区间,0.34 - 0.95)。这些结果表明,在人体内,半胱氨酸共轭物的形成在数量上比PCP的形成是更重要的代谢途径。此外,所发现的相关性表明PCBT是HCB体内剂量和谷胱甘肽介导代谢的良好尿液标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26c9/1469858/32e9b2069fe7/envhper00314-0081-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26c9/1469858/838d11704ebb/envhper00314-0079-a.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26c9/1469858/32e9b2069fe7/envhper00314-0081-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26c9/1469858/838d11704ebb/envhper00314-0079-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26c9/1469858/8c90dddf56a6/envhper00314-0080-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26c9/1469858/25d02dfdff8e/envhper00314-0080-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26c9/1469858/990925e07fc0/envhper00314-0081-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26c9/1469858/32e9b2069fe7/envhper00314-0081-b.jpg

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