The bio-distribution of the neurotoxic 1,2-diethylbenzene (1,2-DEB) was studied in male Sprague-Dawley rats after intravenous administration of [(14)C] 1,2-DEB (1 mg kg(-1)). The highest concentrations of [(14)C] non-volatile metabolites, determined by whole-body auto-radiography, were in the nasal cavity, ethmoid turbinates and in kidney.
Whatever the time after dosing, the [(14)C] concentrations in the cerebrum, cerebellum, spinal cord and lung were lower than those in the blood.
In contrast, after killing of batch of administered rats, the [(14)C] concentrations in the brain homogenates were higher than in plasma for 5-15 min.
In addition, the [(14)C] concentrations in the lung were higher than in the plasma for 24 h post-dose. Moreover, the concentrations of unchanged 1,2-DEB and one of its metabolites, 1-(2'-ethylphenyl)ethanol (1,2-EPE) in the brain, were higher than in the plasma until 1 h post-dose. The concentrations of 1,2-DEB in the blood cells were tenfold higher than in the plasma.
The clearance of unchanged 1,2-DEB in the whole blood and in the blood cells was 6.4 and 3.9 ml min(-1), respectively.
The apparent half-life of unchanged 1,2-DEB in plasma is very fast (5 min) which suggests a quick distribution and/or metabolism in liver and/or other tissues such as the lung.
In conclusion, unchanged 1,2-DEB has a high affinity for the brain and blood cells and its concentrations in plasma and brain decreased rapidly with time.
2008-08-28
Eng.
Archives of Toxicology
Institut National de Recherche et de Sécurité, Avenue de Bourgogne, Vandoeuvre Cedex, France. jean-paul.payan [at] inrs.fr
Arch Toxicol. 2008 Sep;82(9):591-600
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