The Role of The Manganese for The Human Health

Some elements in small concentrations are vital for the normal functioning of the human body, but in high concentrations, they may be a threat to its development and normal functioning, this is the case of manganese.

Manganese is found at low levels in virtually all diets and plays an essential role as a cofactor in many enzymatic reactions in humans and other organisms. This element exists in several forms, both physical and chemical, in the Earth's crust, in water, and in the atmosphere's particulate matter. Because of its outer electron shell configuration, it can donate up to 7 electrons (USEPA, 1984[1] ) and assume different oxidation states but in living organisms, Mn is found mainly as Mn2+, Mn3+ and possibly as Mn4+ (Archibald and Tyree, 1987[2] ). While essential biological functions linked to Mn depend on its oxidation state, little is known about how the oxidation state of elevated Mn exposures affect cellular uptake, and function/toxicity (Reaney,2002).

Manganese ingestion represents the main route of human exposure, although inhalation also occurs, predominantly in occupationally exposed groups. Regardless of the intake, Mn levels in biological tissues remain stable as a result of homeostatic mechanisms that effectively regulate the absorption and excretion of this metal. It is also well known, however, that chronic exposure to elevated airborne levels of manganese (Mn) results in adverse neurological, reproductive, and respiratory effects (Mergier et al., 1994, Bader et al., 1999, Aschner and Dorman, 2006, ). This was discovered as early as 1837 when Couper observed neurological problems in workers employed in grinding manganese oxide used in the manufacture of bleaching powder (Guilarte 2010).

Industrial emissions are the main source of manganese anthropogenic release to the air, especially dust and smoke containing manganese dioxide and manganese tetroxide — occurring mainly during the ore mining, crushing, and smelting as well as during steel production (Schiele, 1991). Alternative sources of manganese incorporation to the air are fossil fuels combustion and resuspension of manganese-containing soils (ATSDR, 2000[3]).

Several studies on exposure cases related to mining and manufacturing activities have found a relationship of Mn inhalation with an increased risk of a broad clinical symptoms spectrum. Amongst others, there are reports of some nonspecific neurological symptoms as postural instability, mood and psychiatric changes (i.e., depression, agitation, hallucinations) (Mena et al., 1967 ) and triggering or acceleration of similar symptoms to those of the Parkinson’s disease (PD) (Rodier, 1955; Tanaka & Lieben, 1969; Huang et al., 1989, 1998; Roels et al., 1987a, 1992; Wang et al., 1989; Mergler et al., 1994; Hochberg et al., 1996; Bader et al., 1999), such as bradykinesia, rigidity, tremor, gait disturbance, postural instability and dystonia and/or ataxia (Josephs et al., 2005 ).

Notwithstanding, for some researchers, this relationship remains questionable, taking into account the current clinical, toxicological, and epidemiological evidence, which is not conclusive regarding the existence of such a relationship, based on the argument that from 1 million welders worldwide and until 2007, only approximately 15 case reports were published in the medical literature describing clinical neurological symptoms in those exposed individuals. The numerous epidemiological studies conducted on welders over the last half-century were focused primarily on evaluating respiratory health effects (Santamaría, et al. 2007[4]).

Some studies aiming to estimate the neurological health impact of low-level Mn exposure on non-occupationally exposed population, have employed a number of sensitive tests designed to detect signs of neuropsychological and neuromotor deficits in the absence of overt symptoms (Iregren 1990, 1994, 1999), but they are scarce. According to Zoni and Lucchini (2013), a total of 10 articles from January 2011 to 29 July 2012 were published, in five different countries. The reviewed studies suggest that Mn exposure is related to cognitive, motor and behavior deficits in children, but potential limitations of these studies included the lack of validated biomarkers and the lack of consideration of mixed co-exposure with other neurotoxic agents.

Amongst the epidemiological studies conducted in exposed population mentioned by Zoni and Lucchini (2013), those carried out in the manganese region of Molango, State of Hidalgo, Mexico, stand out. Between 1999 and 2017, 34 articles, book chapters, and research thesis have been published about Mn-related issues on this region (Table 1). Nine of those references relate to social concerns and conflicts, 3 of them to diverse environmental effects and the rest are about exposure to Mn and its presumable effects on the population. The most relevant are cross-sectional studies, based on the comparisons of exposed vs. non-exposed communities (e.g. Santos-Burgoa et al. 2001, Rodríguez-Agudelo et al. 2006, Riojas-Rodríguez et al. 2010, Montes et al. 2011, Torres-Agustín et al. 2013).

The goal of this article is to analyze all the information available about articles and some new relevant information related to Mn exposure in the region of Molango, aiming to get a better comprehensive overview of the current situation.