Speciation and Toxicological Relevance of Manganese in Humans (S. 33-34)

Summary

Although manganese is an essential trace element, concerns are rising about the Mn exposure of humans being related to neurotoxic effects. This contribution summarizes aspects of this topic to provide updated information on Mn related investigations including chemical speciation of Mn-compounds. The paper shows considerations on sources of human exposure, like the use of methylcyclopentadienyl Mn tricarbonyl (MMT). Further, the paper deals with Mn levels in the human organism, showing normal Mn concentrations in various matrices, and continues with aspects of Mn toxicology.

Of specific concern is the transfer of Mn to the brain, the relevant neurotoxic target. Therefore, the contribution focuses on recent investigations on Mn speciation at the neural barriers: Mn concentrations in serum samples (before passing neural barriers), were around 1.7 ± 0.8 μg/L (n=5). In size exclusion chromatography most Mn appeared associated to proteins with a molecular mass corresponding to TF and albumin. However, a Mn peak around 700 Da was also observed, which was increasing with total Mn concentration. This finding could point to excess Mn being transported by a low molecular mass (LMM) carrier. Behind neural barriers, in cerebrospinal fluid (CSF), mostly LMM Mn ligands were found.

Using CZE-ICP-DRC-MS it was investigated, which of these ligands were actually present as Mn-complexes. 13 Mnspecies were monitored in CSF samples, most of them being identified: Mn-histidine, Mnfumarate, Mn-malate, inorganic Mn, Mn-oxal-acetate, Mn-α-keto-glutarate, Mn carrying NAD, Mn-citrate and Mn-adenosin. By far the most abundant Mn-species was Mn-citrate showing a concentration of 0.7 ± 0.1 μg Mn/L.

Introduction

Mn is an essential trace element for human beings. It is a component of several enzymes [1]. Further important functions of Mn include its essentiality for normal bone structure [1]. As early as 1837 the first case of occupational Mn intoxication had been reported. Since that time a large number of studies have been performed to investigate the uptake, metabolism, transport and toxicity of Mn predominantly on the basis of animal models. Several reviews on Mn have been published with focus on its (neuro-) toxicity from a medical or toxicological point of view [2, 3, 4] however, until recently Mn in biomedical samples was not the subject of element speciation analysis.

This contribution summarizes current knowledge about Mn exposure for humans, Mn uptake, metabolism and neurotoxicity, and finally some new developments in Mn speciation at the neural barriers are shown. Specifically the distribution of Mn to different molecular-size fractions of serum or CSF is described. SEC coupled online to ICP-DRC-MS was employed to analyze Mn species in serum (before passing barriers) and CSF (behind the barriers). CSF was then further analyzed by CZE-ICP-DRC-MS for improved identification of Mn species. More detailed information about the aspects and described investigations is given in references [5, 6, 7]."