The Yushchenko Dioxin Poisoning: Chronology and Pharmacokinetics

Ryan, John

doi:10.1002/9781118184141.ch18

Cited by 2 publications

(2 citation statements)

References 11 publications

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“…A few hours after dinner in Kiev on 5 September 2004, a 50year-old male patient suddenly became severely ill. Hospital work-up revealed gastritis, colitis with multiple ulcers, hepatitis, and pancreatitis, all compatible with poisoning by an ''unknown substance'' because testing for thallium, arsenic, antimony, mercury, and lead was negative (Ryan, 2011). Severe facial edema appeared 2 weeks after the poisoning (W2 a.p.).…”

Section: Dioxin-induced Skin Lesions Progress Over Months While Inter...mentioning

confidence: 99%

The Cutaneous Lesions of Dioxin Exposure: Lessons from the Poisoning of Victor Yushchenko

Saurat

Kaya

Saxer-Sekulic

et al. 2011

Toxicological Sciences

122

135

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Several million people are exposed to dioxin and dioxin-like compounds, primarily through food consumption. Skin lesions historically called "chloracne" are the most specific sign of abnormal dioxin exposure and classically used as a key marker in humans. We followed for 5 years a man who had been exposed to the most toxic dioxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), at a single oral dose of 5 million-fold more than the accepted daily exposure in the general population. We adopted a molecular medicine approach, aimed at identifying appropriate therapy. Skin lesions, which progressively covered up to 40% of the body surface, were found to be hamartomas, which developed parallel to a complete and sustained involution of sebaceous glands, with concurrent transcriptomic alterations pointing to the inhibition of lipid metabolism and the involvement of bone morphogenetic proteins signaling. Hamartomas created a new compartment that concentrated TCDD up to 10-fold compared with serum and strongly expressed the TCDD-metabolizing enzyme cytochrome P450 1A1, thus representing a potentially significant source of enzymatic activity, which may add to the xenobiotic metabolism potential of the classical organs such as the liver. This historical case provides a unique set of data on the human tissue response to dioxin for the identification of new markers of exposure in human populations. The herein discovered adaptive cutaneous response to TCDD also points to the potential role of the skin in the metabolism of food xenobiotics.

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Section: Dioxin-induced Skin Lesions Progress Over Months While Inter...mentioning

confidence: 99%

The Cutaneous Lesions of Dioxin Exposure: Lessons from the Poisoning of Victor Yushchenko

Saurat

Kaya

Saxer-Sekulic

et al. 2011

Toxicological Sciences

122

135

View full text Add to dashboard Cite

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“…In December, a sample of his blood sent to a lab in Amsterdam appeared to be contaminated by dioxin-like compounds that activate the AhR signalling pathway, and in January 2005, a chemical analysis performed in Dübendorf (Switzerland) revealed a blood concentration of 110 ng TCDD/g (lw), i.e., more than 5,000 times higher than the global TCDD equivalent of toxicity (TEQ) found in the general population, and corresponding to a body dose of about 2 mg TCDD. It was clear that during his dinner on 5 September 2004, it had been poisoned by TCDD ( McKee, 2009 ; Sorg et al, 2009 ; Ryan, 2011 ).…”

Section: The Case Of Victor Yushchenkomentioning

confidence: 99%

Development of skin diseases following systemic exposure: example of dioxins

Sorg,

Saurat

2023

Front. Toxicol.

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Most skin manifestations of exposure to toxic compounds are a consequence of a direct contact with the toxicants. However, some toxicants may reach the skin following systemic exposure, and promote skin diseases. Good examples of such chemicals are dioxin-like compounds. This family of lipophilic molecules comprises polychlorinated (dibenzodioxins, dibenzofurans and biphenyls). The most potent member of this family is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Following oral ingestion of as little as a few mg TCDD, skin lesions appear in a couple of weeks, starting from the face and diffuse then on the trunk and limbs. This syndrome was historically called “chloracne” and the skin lesions have now been shown to be skin hamartoma induced by TCDD. Sweat glands release their lipid content on the surface of the skin by a holocrine secretion, and so any lost sebocyte should be transmitted to progenitor cells to differentiate and migrate to the sebaceous gland to replace the lost sebocyte. TCDD acts by inducing a switch in this signal and skin hamartoma develop in place of new sebocytes.

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The Yushchenko Dioxin Poisoning: Chronology and Pharmacokinetics

Cited by 2 publications

References 11 publications

The Cutaneous Lesions of Dioxin Exposure: Lessons from the Poisoning of Victor Yushchenko

The Cutaneous Lesions of Dioxin Exposure: Lessons from the Poisoning of Victor Yushchenko

Development of skin diseases following systemic exposure: example of dioxins

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