2005 Volume 49 Issue 1 Pages 3-23
Toluene and xylenes with one and two methyl groups in a benzene ring are typical methylbenzenes used widely in many industries and are not so harmful in comparison with benzene. The lower toxicity of these methylbenzenes is due to the main metabolic routes initiated by the methyl group oxidation through the reaction with active oxygen in living bodies. In these methylbenzenes, the main metabolic route is the methyl group oxidation (benzylalchols) → benzoic acids → hippuric acids (glycine conjugation), which is regarded as less toxic. By way of example, benzoic acid is easily metabolized to form hippuric acid in urine, which is permissible for the high level usage of food additives. Here, the substitution of benzene hydrogen by methyl group has been called safe replacement. On the other hand, the main metabolic route of benzene is ring oxidation (epoxide formation) → phenol, which is shown by carcinogenic and liver damage. Recently, urinary metabolites varying with hippuric acids in safe replacement routes have been detected largely following methyl groups increases in methylbenzenes. In particular, the mercapturic acids and phenols are notable in o-xylene and trimethylbenzenes with three methyl groups. Trimethylbenzenes having high boiling points are used largely as the solvents for building materials and furniture and are reported to be at high levels indoors. In this review, the metabolic routes of methylbenzenes through reactions with active oxygen (superoxide anion radical) in living bodies and indoor air pollution, such as related to sick house syndrome, are discussed on the basis of our recent studies on the urinary metabolites of rats.
