DOSE-DEPENDENT SUPPRESSION OF TOLUENE METABOLISM BY ISOPROPYL-ALCOHOLAND METHYL ETHYL KETONE AFTER EXPERIMENTAL EXPOSURE OF RATS

In order to examine possible suppression of toluene metabolism due to coexposure to other solvents, female Wistar rats were exposed for 8 h to toluene alone (at 50 or 100 ppm), or in combination with either met hyl ethyl ketone (at 50, 100, 200 or 400 ppm) or isopropyl alcohol (at 50, 100, 200, 400, 800 or 1600 ppm). Urine samples were collected for 24 h after initiation of each exposure, and subjected to analysis for two toluene metabolites, hippuric acid and o-cresol, both by HPLC. Th e excretion of hippuric acid, a major metabolite, was not modified whe n the concentrations of methyl ethyl ketone or isopropyl alcohol were low, i.e. 100 ppm or below, whereas it was reduced when methyl ethyl k etone or isopropyl alcohol concentrations were twice or more times hig her than that of toluene. There were no changes in any cases in excret ion of o-cresol, a minor metabolite. The observation after coexposure to methyl ethyl ketone or isopropyl alcohol at low concentration is in line with the negative interaction between toluene and methyl ethyl k etone as well as between toluene and isopropyl alcohol after occupatio nal exposures at low concentrations. Metabolic interaction may take pl ace when the exposure intensity is high, as observed in the present st udy and also after experimental exposure of volunteers to toluene and m-xylene, or occupational exposure to benzene and toluene.