The Mutagenicity and Carcinogenicity of Inorganic Manganese Compounds: A Synthesis of The Evidence

Abstract

Manganese (Mn), a naturally occurring element present in many foodstuffs, is an essential trace element with many biological functions. In industry, inorganic Mn compounds have a range of different applications, although the majority of Mn is used to make alloys and steel. For the general population, the major source of exposure to Mn is dietary, although drinking water may constitute an additional source in some regions. However, in occupationally exposed humans, inhalation of Mn is likely to be an important additional route. In general, Mn and its inorganic compounds are considered to possess low mutagenic or carcinogenic potential compared with some heavy metals. In this review, an up-to-date analysis of the available published studies on the carcinogenic and genotoxic potential of inorganic Mn is provided (organic Mn compounds are not considered). The current literature indicates that Mn may be weakly mutagenic in vitro and possibly clastogenic in vivo, with unknown genotoxic effects in humans; the possible mechanisms underlying these effects are discussed. The experimental evidence on carcinogenicity (quantitative increase in incidence of thyroid tumors in mice but not rats) does not provide any clear evidence, while the available occupational and environmental epidemiological evidence is equivocal as to whether exposure to inorganic Mn is associated with a significant cancer risk. Hence, it is concluded that there is insufficient evidence to indicate that inorganic Mn exposure produces cancer in animals or humans.

Role of Emerging Environmental Risk Factors in Thyroid Cancer: A Brief Review

“…This suggests that excessive Mn dose exposure during gestation is linked to pathological neurodevelopmental outcomes due to altered thyroid hormones’ levels. Experimental evidence about quantitative increase in the incidence of thyroid tumors in exposed mice to Mn does not provide any clear evidence; in addition, the available occupational and environmental epidemiological evidence is still equivocal [48].…”

Reference values of cadmium, arsenic and manganese in blood and factors associated with exposure levels among adult population of Rio Branco, Acre, Brazil

“…For the general population, the majority of Mn is obtained from the diet since it occurs naturally in almost all foodstuffs (Gerber et al, 2002). Excessive Mn exposure can result in adverse effects on lungs, liver, kidney and the central nervous system (ATSDR, 2008), but there is insufficient evidence to indicate that Mn exposure produces cancer in humans (Assem et al, 2011).…”

Emergency Do Not Consume/Do Not Use concentrations for potassium permanganate in drinking water

“…The EPA has provided manganese with a weight-of-evidence classification D -not classifiable as to human carcinogenicity.'' Assem et al 161 considered the 'rodent data do not provide any clear evidence that Mn exposure is carcinogenic and the epidemiologic evidence is at best equivocal'.…”

“…International Programme on Chemical Safety (IPCS) 93 and Assem et al 161 reviewed the in vivo and in vitro genotoxicity data for KMnO 4 and related Mn compounds, including the sulfate and chloride salts. KMnO 4 has been associated with micronuclei or chromosomal aberrations in vivo 121 or in vitro 162 in some studies but not in others.…”

“…163 The IPCS 93 concluded that the results of in vitro studies show that some forms of Mn have mutagenic potential, but the results of in vivo studies in mammals are not consistent. Therefore, Assem et al 161 concluded that Mn might be ‘weakly mutagenic in vitro and possibly clastogenic in vivo but with unknown genotoxic effects in humans’.…”