TOXICOKINETICS OF 1,2,4-TRIMETHYLBENZENE IN HUMANS EXPOSED TO VAPORS OF WHITE SPIRIT - COMPARISON WITH EXPOSURE TO 1,2,4-TRIMETHYLBENZENE ALONE

This study compares the toxicokinetics of inhaled 1,2,4-trimethylbenze ne (124TMB) in men exposed to white spirit with that previously observ ed in the same individuals exposed to 124TMB alone. The appropriatenes s of using dimethylhippuric acid (DMHA) metabolites of 124-, 123- and 135TMB in urine as biomarkers of exposure is also addressed and the ki netics of n-decane, n-undecane and 123TMB is investigated. The toxicok inetics of 124TMB was studied in nine male, healthy volunteers exposed to solvent vapours in an exposure chamber for 2 h during a work load of 50 W. The subjects were exposed to 2 ppm (11 mg/m(3)) of 124TMB dur ing exposure to 300 mg/m3 of white spirit. The 124TMB isomer was analy sed in blood, urine and exhaled air by gas chromatography. The DMHA me tabolites of all three TMB isomers were analysed in urine by high-perf ormance liquid chromatography. The results were compared with previous ly published exposures to 2 and 25 ppm (120 mg/m(3)) of 124TMB vapour alone. In addition, the occurrence of acute effects was studied by mea ns of a questionnaire. Irritation and central nervous system (CNS) sym ptoms were recorded by ratings on a 100 mm visual analogue scale. Bloo d levels of 124TMB and excretion rates of 3,4-DMHA in urine were marke dly elevated both during and after exposure to white spirit compared t o the same exposure level of 124TMB alone. No irritation or CNS effect s were reported in the questionnaire at any exposure condition. It app ears that components in white spirit interfere with the metabolic elim ination of 124TMB. This should be considered in biological exposure mo nitoring as well as in risk assessment.