Toxicokinetics of Inhaled Trimethylbenzenes in Man

The objective of this study was to determine the uptake and disposition of inhaled trimethylbenzenes (TMBs) in man. The toxicokinetics were studied in 10 male, healthy volunteers exposed to TMB vapor in an exposure chamber for 2 hr during 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, and to 2 ppm of 1,2,4-TMB. The TMB isomers were analyzed in blood, urine, and exhaled air by gas chromatography. The relative respiratory uptake was in the range 56–64%. The elimination of TMBs was moderate compared to other aromatic solvents, with a total blood clearance of 0.6–1.0 liter hr−1kg−1. Large volumes of distribution (30–39 liters/kg) and long terminal half-lives of the TMBs in blood (78–120 hr) imply extensive accumulation in adipose tissue. Exhalation during and postexposure accounted for 20–37% of the absorbed amount, whereas the urinary excretion of unchanged TMBs was low (≤0.002%). The kinetics of 1,2,4-TMB seemed linear up to 25 ppm. In addition, the occurrence of symptoms of acute effects was studied by means of a questionnaire. The subjects rated the degree of irritation and central nervous system symptoms on a 100-mm visual analog scale. No discomfort was reported at these exposure conditions.