The disposition and metabolism of durene (1,2,4,5-tetramethylbenzene) in rats.

Abstract

The organ and tissue distribution, excretion and metabolism of [3H]1,2,4,5-tetramethylbenzene ([3H]durene) in male Wistar albino rats were investigated following a single i.p. administration (40 mg/kg) and within 9 days after five daily repeated administrations. Urine proved to be the main route of tritium excretion. Within the first 24 h after a single administration 69% of the radioactivity was excreted in the urine and only 9% in the feces. The highest level of tritium binding was found in the fat tissue, liver, kidneys and adrenal glands. The accumulation of tritium in the plasma proceeded with a kinetic constant of 0.49 h(-1), whereas the half-life of radioactivity decay amounted to about 6.3 h. In erythrocytes, the tritium level was found to be about three times lower than in blood plasma. The total amount eliminated during the 9 days following repeated administration was about 94% of the five doses given. The highest level of tritium was found in fat tissue and adrenal glands, followed by the liver, kidneys, sciatic nerve and muscle. A gradual decline in tritium levels was observed during the following 4 days in most tissues to reach about 2% of the dose given. The main urinary metabolites resulting from the administration of durene were 2,4,5-trimethylbenzyl alcohol (about 22%), 4,5-dimethyl-1,2-benzdialdehyde (about 19%), 2,4,5-trimethylbenzaldehyde (about 19%) and 2,4,5-trimethylbenzoic acid (about 16%). The oxygen-containing metabolites accounted for almost 80%, whereas sulphur-containing metabolites accounted for approximately 10% of the products of biotransformation. In conclusion, most of the durene administered has a relatively rapid turnover rate, with minor levels retained in the tissues for longer time periods.