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2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) poisoning in Victor Yushchenko: identification and measurement of TCDD metabolites.

https://arctichealth.org/en/permalink/ahliterature95137
Source
Lancet. 2009 Oct 3;374(9696):1179-85
Publication Type
Article
Date
Oct-3-2009
Author
Sorg O.
Zennegg M.
Schmid P.
Fedosyuk R.
Valikhnovskyi R.
Gaide O.
Kniazevych V.
Saurat J-H
Author Affiliation
Dermato-Toxicology, Swiss Centre for Applied Human Toxicology, and Department of Dermatology, University Hospital, Geneva, Switzerland.
Source
Lancet. 2009 Oct 3;374(9696):1179-85
Date
Oct-3-2009
Language
English
Publication Type
Article
Keywords
Adipose Tissue - chemistry
Biopsy
Drug Residues - analysis - metabolism
Fatal Outcome
Feces - chemistry
Forensic Medicine - methods
Half-Life
Homicide
Humans
Male
Middle Aged
Politics
Substance Abuse Detection - methods
Sweat - chemistry
Tetrachlorodibenzodioxin - analysis - chemistry - metabolism - poisoning
Time Factors
Ukraine
Abstract
BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: University of Geneva Dermatology Fund, and Swiss Centre for Applied Human Toxicology.
Notes
Comment In: Lancet. 2009 Oct 3;374(9696):1131-219660808
PubMed ID
19660807 View in PubMed
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