Daughtrey W C, Gill M W, Pritts I M, Douglas J F, Kneiss J J, Andrews L S
Exxon Biomedical Sciences, Inc. East Millstone, NJ 08875, USA.
J Appl Toxicol. 1997 May;17 Suppl 1:S57-64. doi: 10.1002/(sici)1099-1263(199705)17:1+<s57::aid-jat411>3.3.co;2-1.
Methyl tertiary-butyl ether (MTBE) is an oxygenate that is added to gasoline to boost octane and enhance combustion, thereby reducing carbon monoxide and hydrocarbon tailpipe emissions. The acute and subchronic neurotoxicity of MTBE were evaluated in rats using a functional observation battery (FOB), measures of motor activity (MA) and a neuropathological evaluation. In the acute study, rats were exposed once to 0, 800, 4000 or 8000 ppm MTBE by inhalation for 6 h and then evaluated three times over a 24-h period. In the FOB evaluations, treatment-related effects were seen at the 1-h session immediately following exposure and were indicative of transient central nervous system (CNS) depression. Effects were most apparent in the high-dose group (8000 ppm) but were also evident to a lesser extent in the mid-dose (4000 ppm) group. Labored respiration, ataxia, duck-walk gait and decreases in muscle tone, hind-limb grip strength and treadmill performance were the most frequently noted findings. No significant effects were observed in the FOB when testing was conducted at 6 h and 24 h post-exposure. The pattern of motor activity measured in the different dose groups following exposure was also in keeping with a reversible CNS-depressant effect of MTBE. In the subchronic study, rats were exposed to 0, 800, 4000 or 8000 ppm MTBE for 6 h a day, 5 days per week, for 13 weeks. No persistent or cumulative effects on neurobehavioral function were found. Body weights and absolute brain weights were reduced in the 8000 ppm group, however there were no differences among groups when brain weight was expressed relative to body weight. No histopathological changes were noted in the brains or peripheral nervous tissues of MTBE-exposed animals. In summary, MTBE produced signs of acute reversible CNS depression following exposure to 8000 ppm and, to a lesser extent, to 4000 ppm vapor. The no-observed-adverse-effect level for these effects was 800 ppm in the present study. No persistent or cumulative neurotoxic effects were observed following exposure to MTBE at concentrations up to 8000 ppm for 13 weeks.
甲基叔丁基醚（MTBE）是一种含氧化合物，被添加到汽油中以提高辛烷值并增强燃烧，从而减少一氧化碳和碳氢化合物的尾气排放。使用功能观察组合（FOB）、运动活动测量（MA）和神经病理学评估对大鼠进行MTBE的急性和亚慢性神经毒性评估。在急性研究中，大鼠通过吸入一次性暴露于0、800、4000或8000 ppm的MTBE中6小时，然后在24小时内进行三次评估。在FOB评估中，在暴露后立即进行的1小时时段观察到与治疗相关的效应，表明存在短暂的中枢神经系统（CNS）抑制。这些效应在高剂量组（8000 ppm）中最为明显，但在中剂量组（4000 ppm）中也有较小程度的显现。呼吸急促、共济失调、鸭步步态以及肌张力、后肢握力和跑步机性能下降是最常观察到的结果。暴露后6小时和24小时进行测试时，在FOB中未观察到显著效应。暴露后不同剂量组测量的运动活动模式也与MTBE的可逆性CNS抑制作用一致。在亚慢性研究中，大鼠每天暴露于0、800、4000或8000 ppm的MTBE中6小时，每周5天，持续13周。未发现对神经行为功能有持续或累积效应。8000 ppm组的体重和绝对脑重降低，然而，当脑重相对于体重表示时，各组之间没有差异。在暴露于MTBE的动物的大脑或周围神经组织中未观察到组织病理学变化。总之，暴露于8000 ppm以及在较小程度上暴露于4000 ppm蒸汽的MTBE后会产生急性可逆性CNS抑制的迹象。在本研究中，这些效应的未观察到不良反应水平为800 ppm。在长达13周的时间内暴露于高达8000 ppm的MTBE后，未观察到持续或累积的神经毒性效应。
