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Mechanism of immuno toxicity of dibutyltin clarified

(12.11.2008)


Background:
DBT is part of a class of high toxic and widely distributed chemical compounds called organotins, DBT is most commonly used as an anti-fouling agent in paint, for example in the fishing and shipbuilding industries. It is also used in the production of polyvinyl chloride (PVC) plastic tubes and bottles.

According to co-lead investigators Michael E. Baker, Ph.D., researcher in UC San Diego's Department of Medicine, Division of Nephrology-Hypertension, and Alex Odermatt, Ph.D., at the University of Basel, DBT is closely related to tributyltin (TBT), another well-known pollutant. Concern about the side effects of TBT led the United Nations' International Maritime Organization to organize a global ban on its use (see EVISA News).

The new study:
"TBT is metabolized by the body's liver into DBT," the scientists explained. "Humans are also exposed to DBT by drinking water from PVC pipes. Because it is poorly broken down, DBT remains in the environment and it appears that its toxic effects are more rapid and more pronounced than those of TBT."

Symptoms of organotin exposure can include irritated skin, dizziness, difficulty breathing, and flu-like symptoms. Although long-terms effects in humans are uncertain, large doses of certain organotins have been shown to damage the reproductive and central nervous systems, bone structure, the liver and immune system in mammals.

Combining studies of the effect in cell culture of DBT on the function of a key class of steroid hormone, glucocorticoids, with computer-based analyses of the molecular interaction of DBT and the glucocorticoid receptor (GR), the U.S. and Swiss scientists explained the mechanism by which DBT inhibits transcriptional activity of the GR.

The GR is expressed in almost every cell in the body. Besides important functions in energy metabolism, the GR helps to regulate genes that control the body's immune system. The researchers propose that by blocking GR activation, DBT disrupts the appropriate response of the immune system during inflammation, providing an explanation for some of the toxic effects of this organotin. Even further, these findings raise the possibility that some effects of TBT are primarily caused by its metabolite DBT. 

Source: University of California - San Diego


The original study

Christel Gumy, Charlie Chandsawangbhuwana, Anna A. Dzyakanchuk, Denise V.
Kratschmar, Michael E. Baker, Alex Odermatt, Dibutyltin Disrupts Glucocorticoid Receptor Function and Impairs Glucocorticoid-Induced Suppression of Cytokine Production, PLoS ONE, 3/10 (2008) e3545. doi:10.1371/journal.pone.0003545



Related studies

M.M. Whalen, B.G. Loganathan, K. Kannan, Immunotoxicity of environmentally relevant concentrations of butyltins on human natural killer cells in vitro, Environ. Res. (U.S.A), 81 (1999) 108-116. doi:10.1006/enrs.1999.3968

W. Seinen, J.G. Vos, R. van Krieken, A. Pennink, R. Brands, H. Hooykaas, Toxicity of organotin compounds. III. Suppression of thymus-dependent immunity in rats by di-n-butyltindichloride and di-n-octyltindichloride, Toxicol. Appl. Pharmacol., 42/1 (1977) 213-224.



Related EVISA Resources

EVISA Link Database: Toxicity of organotin compounds
EVISA Link Database: All about DBT


Related News

EVISA News, November 5, 2008: Tributyltin added to U.N. trade watch list
EVISA News, September 18, 2008: Tributyltin canned
EVISA News, June 21, 2008: TBT and other Persistent Man-Made Chemical Pollutants Found in Deep-Sea Octopods and Squids
EVISA News, June 5, 2008: Organotin ban in hull paint begins in September
EVISA News, September 20, 2007: TBT-ban convention ratified
EVISA News, November 16, 2006: A silent pandemic: Industrial chemicals are impairing the brain development of children worldwide
EVISA News, October 11, 2006: TBT from antifouling paint is still endangering marine life, says WWF

last time modified: November 13, 2008









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