The comparative metabolism of mesitylene, pseudocumene, and hemimellitene in rats

Abstract

The principal routes of metabolism of the three isomers of trimethylbenzene, mesitylene, pseudocumene, and hemimellitene, have been quantitatively investigated in rats and rate constants measured for the urinary excretion of conjugates with glycine, glucuronic acid, and sulphuric acid. Approximately 78% of an oral dose of mesitylene is excreted as 3,5-dimethylhippuric acid; an additional 7.6 and 8.2% were excreted as glucuronic and sulphuric acid conjugates. The corresponding values for the glycine, glucuronic and sulphuric acid conjugates of pseudocumene and hemimellitene were 43.2, 6.6, and 12.9% and 17.3, 19.4, and 19.9%, respectively. It is considered that 3,4-dimethylbenzoic acid is the principal metabolite of pseudocumene. The relatively greater toxicity of hemimellitene may in part be attributed to the fact that it is more slowly metabolized and excreted than either mesitylene or pseudocumene. It has been established that the effect of phenobarbital administration on the of metabolism of all three compounds is due primarily to an increase in the rate of aromatic hydroxylation rather than in the rate of formation of the corresponding carboxylic acid. By comparing the metabolism of the isomeric di- and trimethylbenzenes, it has been possible to evaluate the influence of the position of the methylsubstituents on the routes of metabolism. © 1975.