Järnberg J, Johanson G, Löf A, Ståhlbom B
Department of Occupational Medicine, National Institute for Working Life, Solna, Sweden.
Arch Toxicol. 1998 Jul-Aug;72(8):483-91. doi: 10.1007/s002040050532.
This study compares the toxicokinetics of inhaled 1,2,4-trimethylbenzene (124TMB) in men exposed to white spirit with that previously observed in the same individuals exposed to 124TMB alone. The appropriateness of using dimethylhippuric acid (DMHA) metabolites of 124-, 123- and 135TMB in urine as biomarkers of exposure is also addressed and the kinetics of n-decane, n-undecane and 123TMB is investigated. The toxicokinetics 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/m3) of 124TM B during exposure to 300 mg/m3 of white spirit. The 124TMB isomer was analysed in blood, urine and exhaled air by gas chromatography. The DMHA metabolites of all three TMB isomers were analysed in urine by high-performance liquid chromatography. The results were compared with previously published exposures to 2 and 25 ppm (120 mg/m3) of 124TMB vapour alone. In addition, the occurrence of acute effects was studied by means of a questionnaire. Irritation and central nervous system (CNS) symptoms were recorded by ratings on a 100 mm visual analogue scale. Blood levels of 124TMB and excretion rates of 3,4-DMHA in urine were markedly elevated both during and after exposure to white spirit compared to the same exposure level of 124TMB alone. No irritation or CNS effects were reported in the questionnaire at any exposure condition. It appears that components in white spirit interfere with the metabolic elimination of 124TMB. This should be considered in biological exposure monitoring as well as in risk assessment.
本研究比较了接触白酒精的男性吸入1,2,4-三甲基苯（124TMB）的毒代动力学与之前在单独接触124TMB的同一批个体中观察到的情况。还探讨了将尿液中124-、123-和135TMB的二甲基马尿酸（DMHA）代谢物用作接触生物标志物的适用性，并研究了正癸烷、正十一烷和123TMB的动力学。在9名健康男性志愿者中研究了124TMB的毒代动力学，这些志愿者在50W的工作负荷下于暴露舱中暴露于溶剂蒸气2小时。在暴露于300mg/m³白酒精的过程中，受试者接触2ppm（11mg/m³）的124TMB。通过气相色谱法分析血液、尿液和呼出气体中的124TMB异构体。通过高效液相色谱法分析尿液中所有三种TMB异构体的DMHA代谢物。将结果与之前发表的单独接触2ppm和25ppm（120mg/m³）124TMB蒸气的情况进行比较。此外，通过问卷调查研究急性效应的发生情况。通过在100mm视觉模拟量表上评分来记录刺激和中枢神经系统（CNS）症状。与单独接触相同暴露水平的124TMB相比，在接触白酒精期间和之后，血液中124TMB水平和尿液中3,4-DMHA的排泄率均显著升高。在任何暴露条件下的问卷调查中均未报告有刺激或CNS效应。看来白酒精中的成分会干扰124TMB的代谢消除。在生物接触监测以及风险评估中都应考虑到这一点。
