Manganese Health Research Program: Phase 2, Core 12
|Research Core Project Number:|
|Research Core Project:||Assessment of Genotoxicity and Carcinogenicity of Inorganic-forms of Manganese|
|Core Principal Investigator (CPI):||Leonard Levy|
|Key Collaborators:||Louise Assem|
This project, undertaken by the Institute of Environment and Health (IEH) was intended to provide the Manganese Health Research Program (MHRP) with an up-to-date critical review of all available published studies on the carcinogenic and genotoxic potential of inorganic forms of manganese. Organic manganese compounds, including petrol additives, were considered to fall outside the scope of the current review.
The carcinogenicity and mutagenicity of manganese compounds was reviewed in 2002 (Gerber et al., 2002) and 2004 (IEH, 2004). This latter review suggested that the knowledge base on the genotoxicity of inorganic manganese was incomplete and conflicting, and that there was only limited information on carcinogenic potential. As a consequence, this project was undertaken by the Institute of Environment and Health (IEH) in order to provide the Manganese Health Research Program (MHRP) with an up-to-date review of all available published studies on the carcinogenic and genotoxic potential of inorganic forms of manganese. Organic manganese compounds, including petrol additives, were considered to fall outside the scope of the current review.
This review has focused on the systematic assessment of the robustness of individual experimental studies (considered against current OECD and other test method guidance and classification schemes) as well as consideration of the significance of the individual findings and overall knowledge base (Section 3). Based on the outcomes of the review phase, an assessment of the strength of the existing evidence was undertaken (Section 4) and any gaps in knowledge were identified (Section 5.1). Recommendations for further testing and guidance on the interpretation and potential consequences of the possible outcomes of the proposed test strategy are also given (Sections 5.1 - 5.3).
Final report submitted to MHRP May 2008
|Scheduled completion date:|
|Completed: May 2009|
Key research accomplishments:
A peer-reviewed paper based on the report but with updated literature was prepared and has been accepted for publication by the Journal of Toxicology and Environmental Health and will be published in 2011. The title of the paper is: The mutagenicity and carcinogenicity of inorganic Manganese compounds: a synthesis of the evidence, by, Farida Louise Assem, Philip Holmes and Leonard Stephen Levy.
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.
Last updated: July 2011