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ToxSci Advance Access published online on December 1, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfj056
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© The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received August 14, 2005
Accepted November 21, 2005

Biotransformation and Toxicokinetics

Styrene-7,8-oxide Burden in Ventilated, Perfused Lungs of Mice and Rats Exposed to Vaporous Styrene

Christiana Hofmann 1, Christian Pütz 1, Brigitte Semder 1, Thomas H. Faller 1, György A. Csanády 2, and Johannes G. Filser 2 *

1 Institute of Toxicology, GSF-National Research Center for Environment and Health, D-85764 Neuherberg, Germany
2 Institute of Toxicology, GSF-National Research Center for Environment and Health, D-85764 Neuherberg, Germany; Institut für Toxikologie und Umwelthygiene, Technische Universität München, München, Germany

* To whom correspondence should be addressed.
Johannes G. Filser, E-mail: johannes.filser{at}gsf.de


  Abstract

Styrene (ST) is an important industrial chemical. In long-term inhalation studies, ST induced lung tumors in mice but not in rats. In order to test the hypothesis that the lung burden by the reactive metabolite styrene-7,8-oxide (SO) would be most relevant for the species-specific tumorigenicity, we investigated the SO burden in isolated lungs of male Sprague-Dawley rats and in-situ prepared lungs of male B6C3F1 mice ventilated with air containing vaporous ST and perfused with a modified Krebs-Henseleit buffer (37°C). ST vapor concentrations were determined in air samples collected in immediate vicinity of the trachea. They were almost constant during each experiment. ST exposures ranged from 50 to 980 ppm (rats) and from 40 to 410 ppm (mice). SO was quantified from the effluent perfusate. Lungs of both species metabolized ST to SO. After a mathematical translation of the obtained ex-vivo data to ventilation and perfusion conditions as they are occurring in vivo, a species comparison was carried out. At ST concentrations of up to 410 ppm, mean SO levels in mouse lungs ranged up to 0.45 nmol/g lung about 2 times higher than in rat lungs at equal conditions of ST exposure. We conclude that the species difference in the SO lung burden is too small to consider the genotoxicity of SO as sufficient for explaining the fact that only mice developed lung tumors when exposed to ST. Another cause has to be considered as driving force for lung tumor development in the mouse.

Keywords: Styrene; styrene-7,8-oxide; mouse; rat; ventilated, perfused lung; inhalation; mode of action.
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