Urinary excretion of dimethylhippuric acids in humans after exposure to trimethylbenzenes

The aim of this study was to determine the urinary excretion of dimethylhippuric acids (DMHAs) in humans after experimental chamber exposure to trimethylbenzene (TMB) vapor. The DMHAs have been put forward as suitable biomarkers of exposure to products containing TMBs such as white spirit and petrol. Ten healthy male volunteers were exposed to TMB vapor in an exposure chamber for 2 h at a work load of 50 W. The subjects were exposed on four occasions, to 25 ppm of 1,2,4-TMB, 1,2,3-TMB, and 1,3,5-TMB, respectively, and 2 ppm of 1,2,4-TMB. Urine was collected from the onset of exposure until the following morning. All six possible DMHA isomers were analyzed by high-performance liquid chromatography. About 22% of the inhaled amount of 1,2,4-TMB was excreted as DMHAs within 24 h, mainly as 3,4-DMHA. The 24-h recovery of 1,2,3-TMB as DMHAs was 11%. Only 3% of the absorbed amount of 1,3,5-TMB was excreted as 3,5,-DMHA. The half-times of the different DMHA isomers ranged from 4 to 16 h. In addition to analysis of DMHAs, the excretion of unconjugated dimethylbenzoic acids in urine was estimated to account for approximately 3% of the dose of all TMBs. In conclusion, the urinary excretion of DMHA isomers may serve as a good indicator of TMB exposure. In this controlled short-term-exposure study the sum of excretion rate of several DMHA isomers reflected exposure more closely than did the excretion rate of any single DMHA.