Uaki H, Kawai T, Mizunuma K, Moon C S, Zhang Z W, Inui S, Takada S, Ikeda M
Kyoto Industrial Health Association, Japan.
Toxicol Lett. 1995 Nov 15;81(2-3):229-34. doi: 10.1016/0378-4274(95)03445-5.
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 methyl 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. The excretion of hippuric acid, a major metabolite, was not modified when the concentrations of methyl ethyl ketone or isopropyl alcohol were low, i.e. 100 ppm or below, whereas it was reduced when methyl ethyl ketone or isopropyl alcohol concentrations were twice or more times higher than that of toluene. There were no changes in any cases in excretion 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 ketone as well as between toluene and isopropyl alcohol after occupational exposures at low concentrations. Metabolic interaction may take place when the exposure intensity is high, as observed in the present study and also after experimental exposure of volunteers to toluene and m-xylene, or occupational exposure to benzene and toluene.
为了研究因同时接触其他溶剂而可能对甲苯代谢产生的抑制作用，将雌性Wistar大鼠单独暴露于甲苯（50或100 ppm）8小时，或与甲乙酮（50、100、200或400 ppm）或异丙醇（50、100、200、400、800或1600 ppm）联合暴露8小时。每次暴露开始后收集24小时的尿液样本，并通过高效液相色谱法对两种甲苯代谢物马尿酸和邻甲酚进行分析。当甲乙酮或异丙醇浓度较低，即100 ppm或更低时，主要代谢物马尿酸的排泄没有改变，而当甲乙酮或异丙醇浓度是甲苯浓度的两倍或更多倍时，马尿酸的排泄减少。次要代谢物邻甲酚的排泄在任何情况下均无变化。低浓度下同时接触甲乙酮或异丙醇后的观察结果与职业低浓度暴露后甲苯与甲乙酮以及甲苯与异丙醇之间的负相互作用一致。当暴露强度较高时，可能会发生代谢相互作用，如本研究中观察到的，以及志愿者实验性暴露于甲苯和间二甲苯后，或职业性暴露于苯和甲苯后。
