An international team of researchers at the University of California, San Diego School of Medicine and the University of Basel in Switzerland have issued a report on the mechanism of toxicity of a chemical compound called dibutyltin (DBT).
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. DOI:
10.1016/0041-008X(77)90211-3
Related EVISA Resources Link Database: Toxicity of organotin compounds Link Database: All about DBT
Related EVISA News
last time modified: May 22, 2024
