Application of pharmacokinetic data to the risk assessment of inhaled manganese
Application of pharmacokinetic data to the risk assessment of inhaled manganese
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DOI：
10.1016/j.neuro.2006.03.003
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发表时间：
2006-09-01
期刊：
影响因子：
3.4
通讯作者：
Andersen, Melvin E.
中科院分区：
文献类型：
--
作者：
Dorman, David C.;Struve, Melanie F.;Andersen, Melvin E.
科学界对锰的神经毒性越来越感兴趣，部分原因是使用甲基环戊二烯基三羰基锰（MMT）作为汽油燃料添加剂，并增强了人们对这种必需金属可能在肝性脑病和其他神经系统疾病中发挥作用的认识。神经毒性通常在较长一段时间内出现，当锰的摄入量超过其消除量时，导致脑锰浓度增加。高剂量口服、吸入或肠外暴露或肝胆清除受损后可发生神经毒性。过去几年完成的研究通过确定导致中枢神经系统和其他目标器官内锰浓度增加的暴露条件，大大提高了我们对吸入锰所造成的健康风险的理解。其中许多研究集中在磷酸盐、硫酸盐和锰的氧化物上，因为这些是在汽车燃烧MMT后形成和排放的。这些研究评估了吸入锰的直接鼻到脑运输的作用，并检查了潜在敏感亚群（如胎儿、新生儿、肝功能受损或锰摄入量低于最佳水平的个体和老年人）中锰毒性动力学的差异。本文回顾了美国环境保护署目前对吸入锰的风险评估，总结了这些当代药代动力学研究，并考虑了这些数据如何为吸入锰后的未来风险评估提供信息。(C) 2006爱思唯尔公司版权所有。
There is increased interest within the scientific community concerning the neurotoxicity of manganese owing in part to the use of methylcyclopentadienyl manganese tricarbonyl (MMT) as a gasoline fuel additive and an enhanced awareness that this essential metal may play a role in hepatic encephalopathy and other neurologic diseases. Neurotoxicity generally arises over a prolonged period of time and results when manganese intake exceeds its elimination leading to increases in brain manganese concentration. Neurotoxicity can occur following high dose oral, inhalation, or parenteral exposure or when hepatobiliary clearance of this metal is impaired. Studies completed during the past several years have substantially improved our understanding of the health risks posed by inhaled manganese by determining exposure conditions that lead to increased concentrations of manganese within the central nervous system and other target organs. Many of these studies focused on phosphates, sulfates, and oxides of manganese since these are formed and emitted following MMT combustion by an automobile. These studies have evaluated the role of direct nose-to-brain transport of inhaled manganese and have examined differences in manganese toxicokinetics in potentially sensitive subpopulations (e.g., fetuses, neonates, individuals with compromised hepatic function or sub-optimal manganese intake, and the aged). This manuscript reviews the U.S. Environmental Protection Agency's current risk assessment for inhaled manganese, summarizes these contemporary pharmacokinetic studies, and considers how these data could inform future risk assessments of this metal following inhalation. (C) 2006 Elsevier Inc. All rights reserved.