INHALATION TOXICOKINETICS OF 1,2,4-TRIMETHYLBENZENE IN VOLUNTEERS - COMPARISON BETWEEN EXPOSURE TO WHITE SPIRIT AND 1,2,4-TRIMETHYLBENZENE ALONE

The objective of this study was to compare the toxicokinetics of inhal ed 1,2,4-trimethylbenzene (1,2,4-TMB) in man after exposure to white s pirit with that observed after exposure to 1,2,4-TMB alone. TMBs occur mainly in petroleum products and the TMBs or their metabolites have b een suggested as suitable biomarkers of exposure to white spirit and o ther distillation products. The toxicokinetics were studied in 9 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 11 mg /m(3) of 1,2,4-TMB on two occasions; during exposure to 1,2,4-TMB vapo ur alone and during exposure to 300 mg/m(3) of white spirit. The 1,2,4 -TMB isomer was analyzed in blood and exhaled air by gas chromatograph y. In addition, a major urinary metabolite of 1,2,4-TMB, 3,4-dimethylh ippuric acid (3,4-DMHA), was analyzed by high performance liquid chrom atography. Further the occurrence of acute effects was studied by mean s of a questionnaire. Irritation and central nervous system symptoms w ere recorded by ratings on a 100-mm visual analogue scale. Blood level s of 1,2,4-TMB and excretion rates of 3,4-DMHA. in urine were markedly elevated both during and after exposure to white spirit as compared t o exposure to TMB alone. Thus, it appears that components in white spi rit inhibit the metabolic elimination of 1,2,4-TMB. This should be con sidered in biological exposure monitoring as well as in risk assessmen t. No irritation or central nervous system effects were reported at th ese conditions. (C) 1997 Elsevier Science B.V.