Järnberg J, Johanson G, Löf A, Ståhlbom B
National Institute for Working Life, Department of Toxicology and Chemistry, Solna, Sweden.
Sci Total Environ. 1997 Jun 20;199(1-2):65-71. doi: 10.1016/s0048-9697(97)05482-x.
The objective of this study was to compare the toxicokinetics of inhaled 1,2,4-trimethylbenzene (1,2,4-TMB) in man after exposure to white spirit with that observed after exposure to 1,2,4-TMB alone. TMBs occur mainly in petroleum products and the TMBs or their metabolites have been suggested as suitable biomarkers of exposure to white spirit and other 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/m3 of 1,2,4-TMB on two occasions; during exposure to 1,2,4-TMB vapour alone and during exposure to 300 mg/m3 of white spirit. The 1,2,4-TMB isomer was analyzed in blood and exhaled air by gas chromatography. In addition, a major urinary metabolite of 1,2,4-TMB, 3,4-dimethylhippuric acid (3,4-DMHA), was analyzed by high performance liquid chromatography. Further the occurrence of acute effects was studied by means of a questionnaire. Irritation and central nervous system symptoms were recorded by ratings on a 100-mm visual analogue scale. Blood levels 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 to exposure to TMB alone. Thus, it appears that components in white spirit inhibit the metabolic elimination of 1,2,4-TMB. This should be considered in biological exposure monitoring as well as in risk assessment. No irritation or central nervous system effects were reported at these conditions.
本研究的目的是比较人体吸入白酒精后1,2,4-三甲基苯（1,2,4-TMB）的毒代动力学与单独吸入1,2,4-TMB后的情况。TMBs主要存在于石油产品中，TMBs或其代谢产物被认为是接触白酒精和其他蒸馏产品的合适生物标志物。在9名健康男性志愿者中进行了毒代动力学研究，他们在50W的工作负荷下于暴露舱中暴露于溶剂蒸气2小时。受试者在两种情况下暴露于11mg/m³的1,2,4-TMB；一次是单独暴露于1,2,4-TMB蒸气时，另一次是暴露于300mg/m³的白酒精时。通过气相色谱法分析血液和呼出气体中的1,2,4-TMB异构体。此外，通过高效液相色谱法分析1,2,4-TMB的主要尿代谢产物3,4-二甲基马尿酸（3,4-DMHA）。进一步通过问卷调查研究急性效应的发生情况。通过100mm视觉模拟量表评分记录刺激和中枢神经系统症状。与单独暴露于TMB相比，暴露于白酒精期间和之后，血液中1,2,4-TMB水平和尿液中3,4-DMHA排泄率均显著升高。因此，似乎白酒精中的成分抑制了1,2,4-TMB的代谢消除。在生物暴露监测以及风险评估中都应考虑这一点。在这些条件下未报告有刺激或中枢神经系统效应。
