Ingestion of benzoic acid (intermediary metabolite of toluene) by one volunteer subject indicated that the maximum urinary excretion rate of hippuric acid (final metabolite of toluene) was about 190 µmol/min. An almost identical figure for the saturation kinetics of hippuric acid formation has been reported in the literature, and it has been shown to be limited by the availability of glycine for benzoic acid conjugation. The maximum excretory capacity of the kidneys for hippurate is known to be considerably larger than the observed maximum rate of benzoic acid conjugation. In addition the intravenous administration of methylhippuric acid showed that its urinary excretion is rapid, approaching an excretion rate constant of 1.3 h-1. The glycine conjugation of benzoic acid and methylbenzoic acid may well be the ratelimiting step in toluene and, respectively, xylene metabolism. During the inhalation of these solvents, uptake rate may be estimated to equal the full conjugating capacity at a toluene or xylene air concentration of about 780 ppm at rest or of about 270 ppm during moderately heavy work. These data suggest that the body has a relatively large capacity for the conjugation reactions of toluene and xylene metabolism, but the consumption of a large part of easily mobilized glycine may impair the conjugation, and hence excretion, of poorer substrates, e.g., drugs.

Key terms benzoic acid; conjugation; conjugation reaction; hippuric acid; m-methylbenzoic acid; m-methylhippuric acid; m-xylene; m-xylene metabolite; man; toluene; urinary excretion