Bio-distribution study of 1,2-DIETHYLBENZENE (cas 135-01-3) and its main metabolites by whole-body autoradiography and tissue homogenates

Add time:09/29/2019    Source:infona.pl

The bio-distribution of the neurotoxic 1,2-DIETHYLBENZENE (cas 135-01-3) (1,2-DEB) was studied in male Sprague-Dawley rats after intravenous administration of [14C] 1,2-DEB (1 mg kg−1). The highest concentrations of [14C] 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 [14C] 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 [14C] concentrations in the brain homogenates were higher than in plasma for 5–15 min. In addition, the [14C] 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.

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