| Methylcyclopentadienyl manganese tricarbonyl (NWT) is an organic manganese (Mn) compound added to unleaded gasoline in Canada. The primary combustion products of MMT are Mn phosphate, Mn sulfate, and Mn phosphate/sulfate mixture. Concerns have been raised that the combustion products of MMT could be neurotoxic, even at low levels of exposure. The objective of this study is to assess and compare tissue concentration following subchronic inhalation exposure to a mixture of Mn phosphate/sulfate particles in rats exposed at low, intermediate and high levels. This research aims also to assess the neuropathology and neurobehavioral effects associated with exposure to the mixture.; A control group and three groups of 30 male Sprague-Dawley rats were exposed in inhalation chambers for a period of 13 weeks, 5 days per week, 6 hours a day. Exposure concentrations were 3000, 300, and 30 mug/m 3. The neuropathology aspect of this study was to count neuronal cells in globus pallidus, caudate putamen, and frontal cortex. Also the neurobehavioral change was measured by assessing locomotor activity and tremor among groups. In each group, half of the rats were implanted with chronic EMG electrodes in the gastrocnemius muscle of the hind lamb for the purpose of measuring tremor. Tremor assessment was conducted one hour after the last exposure by recording muscle EMG activity for approximately 5 minutes with implanted EMG electrode rats while resting in the cage, walking on the floor, and standing on a vertical 39 cm metal screen grid.; At the end, locomotor activity test was conducted for 36 hours using a computerized autotrack system. Rats were then sacrificed by exsanguinations, and Mn concentration in different tissues (liver, lung, testis, and kidney), blood and brain (caudate putamen, globus pallidus, olfactory bulb, frontal cortex, and cerebellum) were determined by neutron activation analysis. Increased manganese concentrations were observed in blood, kidney, lung, testis, and in all brain sections in the highest exposure group. Mn in the lung and in the olfactory bulb was dose-dependent. Our data indicate that the olfactory bulb accumulated more Mn than other brain regions following inhalation exposure. Biochemical profiles also revealed some significant differences in certain parameters, specifically alkaline phosphatase, urea, and chlorate.; Locomotor activity was significantly increased at 30 and 3000 mug/m 3. The neuronal cell loss was significantly different in all three areas of interest for rats exposed to the highest level of exposure (3000 mug/m 3). The result does not show any sign of tremor. In conclusion, exposure to Mn phosphate/sulfate mixture leads to onset the neuropathological changes in particular area of the brain and causes some neurobehavioral differences among the rats. |
