Influence of particle solubility on the delivery of inhaled manganese to the rat brain: Manganese sulfate and manganese tetroxide pharmacokinetics following repeated (14-day) exposure
Influence of particle solubility on the delivery of inhaled manganese to the rat brain: Manganese sulfate and manganese tetroxide pharmacokinetics following repeated (14-day) exposure
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DOI：
10.1006/taap.2000.9088
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发表时间：
2001-01-15
影响因子：
3.8
通讯作者：
Wong, BA
中科院分区：
文献类型：
--
作者：
Dorman, DC;Struve, MF;Wong, BA
溶解速度会影响金属在肺部的清除，从而影响其向大脑和其他器官的输送。本研究的目的是确定成年雄性Cd大鼠吸入相对可溶的硫酸盐(MnSO4)和不溶性四氧化二锰(Mn3O4)的暴露-反应关系。大鼠暴露于0、0.03、0.3或3 mg Mn/m(3)的MnSO4或Mn3O4中，每天6小时，每周暴露7天(14次)。然后测定暴露结束时嗅球、纹状体、小脑、胆汁、肺、肝脏、股骨、血清和睾丸(n=6只大鼠/浓度/化学物质)的锰浓度和全身锰-54排除量。高剂量(3 mg Mn/m~3)MnSO_4和Mn3O_4暴露组动物体内Mn-54清除率增加。在暴露于大于或等于0.3 mg Mn/m(3)的MnSO4和Mn3O4后，观察到肺中的锰浓度升高。当MnSO4暴露于大于或等于0.3 mg Mn/m(3)时，也观察到嗅球和股骨的锰浓度升高。在暴露于3 mg Mn/m(3)的MnSO4后，观察到纹状体、睾丸、肝脏和胆汁中的锰浓度升高。在暴露于3 mg Mn/m(3)的Mn3O4后，观察到嗅球、纹状体、股骨和胆汁中的锰浓度升高。与类似的Mn3O4暴露水平相比，暴露于MnSO4(3 mg Mn/m(3))的动物肺更低，嗅球和纹状体的锰浓度更高。我们的结果表明，吸入可溶形式的锰会导致比接触不可溶形式的锰后获得更高的脑锰浓度。(C)2001年学术出版社。
Dissolution rate can influence the pulmonary clearance of a metal and thus affect its delivery to the brain and other organs. The goal of this study was to determine the exposure-response relationship for the relatively soluble sulfate (MnSO4) and insoluble tetroxide (Mn3O4) forms of inhaled manganese in adult male CD rats. Rats were exposed 6 h/day for 7 days/week (14 exposures) to either MnSO4 or Mn3O4 at 0, 0.03, 0.3, or 3 mg Mn/m(3). End-of-exposure olfactory bulb, striatum, cerebellum, bile, lung, liver, femur, serum, and testes (n = 6 rats/concentration/chemical) manganese concentrations and whole-body Mn-54 elimination were then determined. Increased whole-body Mn-54 clearance rates were observed in animals from the high-dose (3 mg Mn/m3) MnSO4 and Mn3O4 exposure groups. Elevated manganese concentrations in the lung were observed following MnSO4 and Mn3O4 exposure to greater than or equal to0.3 mg Mn/m(3). Increased olfactory bulb and femur manganese concentrations were also observed following MnSO4 exposure at greater than or equal to0.3 mg Mn/m(3). Elevated striatal, testes, liver, and bile manganese concentrations were observed following exposure to MnSO4 at 3 mg Mn/m(3). Elevated olfactory bulb, striatal, femur, and bile manganese concentrations were observed following exposure to Mn3O4 at 3 mg Mn/m(3). Animals exposed to MnSO4 (3 mg Mn/m(3)) had lower lung and higher olfactory bulb and striatal manganese concentrations compared with levels achieved following similar Mn3O4 exposures. Our results suggest that inhalation exposure to soluble forms of manganese results in higher brain manganese concentrations than those achieved following exposure to an insoluble form of manganese. (C) 2001 Academic Press.