Bio-distribution study of 1,2-diethylbenzene and its main metabolites by whole-body autoradiography and tissue homogenates.
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.
Payan
Jean-Paul
JP
Institut National de Recherche et de Sécurité, Avenue de Bourgogne, Vandoeuvre Cedex, France. jean-paul.payan@inrs.fr
Binet
Stephane
S
Beydon
Dominique
D
Ferrari
Elisabeth
E
D000465:Algorithms; D000818:Animals; D001345:Autoradiography; D001555:Benzene Derivatives / Q000493:pharmacokinetics* / Q000633:toxicity*; D001773:Blood Cells / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D006207:Half-Life; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D001555:Benzene Derivatives; C064750:1,2-diethylbenzene