Sorg O, Zennegg M, Schmid P, Fedosyuk R, Valikhnovskyi R, Gaide O, Kniazevych V, Saurat J-H
Dermato-Toxicology, Swiss Centre for Applied Human Toxicology, and Department of Dermatology, University Hospital, Geneva, Switzerland.
Lancet. 2009 Oct 3;374(9696):1179-85. doi: 10.1016/S0140-6736(09)60912-0. Epub 2009 Aug 5.
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has a long half-life of 5-10 years in human beings as a result of its high lipophilicity, and little or no metabolism. We monitored TCDD, its form, distribution, and elimination in Victor Yushchenko after he presented with severe poisoning.
In late December, 2004, a patient presented with TCDD poisoning; the levels in his blood serum (108000 pg/g lipid weight) were more than 50 000-fold greater than those in the general population. We identified TCDD and its metabolites, and monitored their levels for 3 years using gas chromatography and high-resolution mass spectrometry in samples of blood serum, adipose tissue, faeces, skin, urine, and sweat, after they were extracted and cleaned with different organic solvents.
The amount of unmodified TCDD in the samples that were analysed accounted for about 60% of TCDD eliminated from the body during the same period. Two TCDD metabolites-2,3,7-trichloro-8-hydroxydibenzo-p-dioxin and 1,3,7,8-tetrachloro-2-hydroxydibenzo-p-dioxin-were identified in the faeces, blood serum, and urine. The faeces contained the highest concentration of TCDD metabolites, and were the main route of elimination. Altogether, the different routes of elimination of TCDD and its metabolites accounted for 98% of the loss of the toxin from the body. The half-life of TCDD in our patient was 15.4 months.
This case of poisoning with TCDD suggests that the design of methods for routine assessment of TCDD metabolites in human beings should be a main aim of TCDD research in the metabolomic era.
University of Geneva Dermatology Fund, and Swiss Centre for Applied Human Toxicology.
由于2,3,7,8 - 四氯二苯并 - 对 - 二噁英（TCDD）具有高亲脂性且很少或几乎不发生代谢，其在人体中的半衰期长达5至10年。我们监测了维克托·尤先科出现严重中毒后体内TCDD及其形态、分布和消除情况。
2004年12月下旬，一名患者出现TCDD中毒；其血清中TCDD水平（108000皮克/克脂质重量）比普通人群高出50000多倍。我们鉴定了TCDD及其代谢物，并在血清、脂肪组织、粪便、皮肤、尿液和汗液样本用不同有机溶剂提取和净化后，使用气相色谱和高分辨率质谱对其水平进行了3年监测。
所分析样本中未修饰的TCDD量约占同期体内消除的TCDD的60%。在粪便、血清和尿液中鉴定出两种TCDD代谢物——2,3,7 - 三氯 - 8 - 羟基二苯并 - 对 - 二噁英和1,3,7,8 - 四氯 - 2 - 羟基二苯并 - 对 - 二噁英。粪便中TCDD代谢物浓度最高，是主要的消除途径。总体而言，TCDD及其代谢物的不同消除途径占体内毒素损失的98%。我们这位患者体内TCDD的半衰期为15.4个月。
这例TCDD中毒病例表明，设计人类TCDD代谢物常规评估方法应是代谢组学时代TCDD研究的主要目标。
日内瓦大学皮肤病学基金和瑞士应用人类毒理学中心。
