Normandin Louise, Carrier Gaétan, Gardiner Phillip F, Kennedy Greg, Hazell Alan S, Mergler Donna, Butterworth Roger F, Philippe Suzanne, Zayed Joseph
TOXHUM (Human Toxicology Research Group), Department of Environmental and Occupational Health, Faculty of Medicine, Université de Montréal, C.P. 6128, Succursale Centre-Ville, Montréal, Québec, Canada H3C 3J7.
Toxicol Appl Pharmacol. 2002 Sep 1;183(2):135-45.
Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese (Mn) compound added to unleaded gasoline. It has been suggested that the combustion products of MMT containing Mn, such as manganese phosphate, could cause neurological symptoms similar to Parkinson's disease in humans. The aim of this work was to investigate the exposure-response relationship of bioaccumulation, neuropathology, and neurobehavior following a subchronic inhalation exposure to manganese phosphate in Sprague-Dawley male rats. Rats were exposed 6 h/day, 5 days/week for 13 consecutive weeks at 30, 300, or 3000 microg/m(3) Mn phosphate and compared to controls. Some rats were implanted with chronic EMG electrodes in the gastrocnemius muscle of the hind limb to assess tremor at the end of Mn exposure. Spontaneous motor activity was measured for 36 h using a computerized autotrack system. Rats were then sacrificed by exsanguination and Mn level in different brain tissues and other organs was determined by instrumental neutron activation analysis. Neuronal cell counts were obtained by assessing the sum of five grid areas for the caudate/putamen and the sum of two adjacent areas for the globus pallidus. Increased manganese concentrations were observed in all tissues of the brain and was dose-dependent in olfactory bulb and caudate/putamen. In fact, beginning with the highest level of exposure (3000 microg/m(3)) and ending with the control group, Mn concentrations in the olfactory bulb were 2.47 vs 1.28 vs 0.77 vs 0.64 ppm (P < 0.05) while for the caudate/putamen, Mn concentrations were 1.06 vs 0.73 vs 0.62 vs 0.47 ppm (P < 0.05). The Mn concentrations in lung were also dose-dependent (10.30 vs 1.40 vs 0.42 vs 0.17 ppm; P < 0.05). No statistical difference was observed for loss of neurons in caudate/putamen and globus pallidus. Locomotor activity assessment and tremor assessment did not reveal in neurobehavioral changes between the groups. Our results reinforce the hypothesis that the olfactory bulb and caudate/putamen are the main brain tissues for Mn accumulation after subchronic inhalation exposure.
甲基环戊二烯三羰基锰（MMT）是一种添加到无铅汽油中的有机锰（Mn）化合物。有人认为，含锰的MMT燃烧产物，如磷酸锰，可能会在人类身上引发类似于帕金森病的神经症状。这项工作的目的是研究在Sprague-Dawley雄性大鼠亚慢性吸入磷酸锰后，生物蓄积、神经病理学和神经行为的暴露-反应关系。大鼠每天暴露6小时，每周5天，连续13周暴露于30、300或3000微克/立方米的磷酸锰中，并与对照组进行比较。一些大鼠在后肢腓肠肌植入慢性肌电图电极，以在锰暴露结束时评估震颤。使用计算机自动跟踪系统测量36小时的自发运动活动。然后通过放血处死大鼠，并通过仪器中子活化分析测定不同脑组织和其他器官中的锰水平。通过评估尾状核/壳核的五个网格区域总和以及苍白球的两个相邻区域总和来获得神经元细胞计数。在大脑的所有组织中均观察到锰浓度升高，并且在嗅球和尾状核/壳核中呈剂量依赖性。事实上，从最高暴露水平（3000微克/立方米）开始到对照组结束，嗅球中的锰浓度分别为2.47 ppm、1.28 ppm、0.77 ppm和0.64 ppm（P < 0.05），而尾状核/壳核中的锰浓度分别为1.06 ppm、0.73 ppm、0.62 ppm和0.47 ppm（P < 0.05）。肺中的锰浓度也呈剂量依赖性（10.30 ppm、1.40 ppm、0.42 ppm和0.17 ppm；P < 0.05）。在尾状核/壳核和苍白球中未观察到神经元丢失的统计学差异。运动活动评估和震颤评估未揭示各组之间的神经行为变化。我们的结果强化了这样的假设，即嗅球和尾状核/壳核是亚慢性吸入暴露后锰蓄积的主要脑组织。
