TOXICOKINETICS OF INHALED TRIMETHYLBENZENES IN MAN

The objective of this study was to determine the uptake and dispositio n of inhaled trimethylbenzenes (TMBs) in man. The toxicokinetics were studied in 10 male, healthy volunteers exposed to TMB vapor in an expo sure chamber for 2 hr during a work load of 50 W. The subjects were ex posed on four occasions to 25 ppm of 1,2,4-TMB, 1,2,3-TMB, and 1,3,5-T MB, 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 respirator y 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(-1) kg(-1). Large volumes of distribution (30-39 lite rs/kg) and long terminal half-lives of the TMBs in blood (78-120 hr) i mply extensive accumulation in adipose tissue. Exhalation during and p ostexposure accounted for 20-37% of the absorbed amount, whereas the u rinary excretion of unchanged TMBs was low (less than or equal to 0.00 2%). 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 centr al nervous system symptoms on a 100-mm visual analog scale. No discomf ort was reported at these exposure conditions. (C) 1996 Academic Press , Inc.