Dorman David C, Struve Melanie F, Marshall Marianne W, Parkinson Carl U, James R Arden, Wong Brian A
CIIT Centers for Health Research, 6 Davis Drive, PO Box 12137, Research Triangle Park, NC 27709-2137, USA.
Toxicol Sci. 2006 Jul;92(1):201-10. doi: 10.1093/toxsci/kfj206. Epub 2006 Apr 19.
High-dose human exposure to manganese results in manganese accumulation in the basal ganglia and dopaminergic neuropathology. Occupational manganese neurotoxicity is most frequently linked with manganese oxide inhalation; however, exposure to other forms of manganese may lead to higher body burdens. The objective of this study was to determine tissue manganese concentrations in rhesus monkeys following subchronic (6 h/day, 5 days/week) manganese sulfate (MnSO(4)) inhalation. A group of monkeys were exposed to either air or MnSO(4) (0.06, 0.3, or 1.5 mg Mn/m(3)) for 65 exposure days before tissue analysis. Additional monkeys were exposed to MnSO(4) at 1.5 mg Mn/m(3) for 15 or 33 exposure days and evaluated immediately thereafter or for 65 exposure days followed by a 45- or 90-day delay before evaluation. Tissue manganese concentrations depended upon the aerosol concentration, exposure duration, and tissue. Monkeys exposed to MnSO(4) at > or = 0.06 mg Mn/m(3) for 65 exposure days or to MnSO(4) at 1.5 mg Mn/m(3) for > or = 15 exposure days developed increased manganese concentrations in the olfactory epithelium, olfactory bulb, olfactory cortex, globus pallidus, putamen, and cerebellum. The olfactory epithelium, olfactory bulb, globus pallidus, caudate, putamen, pituitary gland, and bile developed the greatest relative increase in manganese concentration following MnSO(4) exposure. Tissue manganese concentrations returned to levels observed in the air-exposed animals by 90 days after the end of the subchronic MnSO(4) exposure. These results provide an improved understanding of MnSO(4) exposure conditions that lead to increased concentrations of manganese within the nonhuman primate brain and other tissues.
人类高剂量接触锰会导致锰在基底神经节中蓄积以及多巴胺能神经病理学改变。职业性锰神经毒性最常与吸入氧化锰有关；然而，接触其他形式的锰可能会导致更高的体内负荷。本研究的目的是确定恒河猴在亚慢性（每天6小时，每周5天）吸入硫酸锰（MnSO₄）后组织中的锰浓度。一组猴子在进行组织分析前，暴露于空气或MnSO₄（0.06、0.3或1.5毫克锰/立方米）中65天。另外的猴子暴露于1.5毫克锰/立方米的MnSO₄中15或33天，然后立即进行评估，或者暴露65天，随后在评估前延迟45或90天。组织中的锰浓度取决于气溶胶浓度、暴露持续时间和组织类型。暴露于≥0.06毫克锰/立方米的MnSO₄中65天或暴露于1.5毫克锰/立方米的MnSO₄中≥15天的猴子，其嗅上皮、嗅球、嗅皮质、苍白球、壳核和小脑中的锰浓度增加。嗅上皮、嗅球、苍白球、尾状核、壳核、垂体和胆汁在暴露于MnSO₄后锰浓度的相对增加最大。在亚慢性MnSO₄暴露结束后90天，组织中的锰浓度恢复到空气暴露动物中观察到的水平。这些结果有助于更好地理解导致非人类灵长类动物大脑和其他组织中锰浓度增加的MnSO₄暴露条件。
