Manganese dioxide

Endpoint summary

Additional information

In vitro studies

a- bacterial test

As reported in SIDS Dossier of MnO2 approved at SIAM 25 (17 -18 October 2007) with reference to unpublish report National Institute of Environmental Research (NIER), Korea, 2006, In vitro bacterial reverse mutation test of manganese dioxide (Report No. G01-06044) tested by Medvill Bacterial reverse mutation test (Ames test) is negative regarding to manganese dioxide in both the presence and absence of a metabolising system. Cytotoxicity was observed at 1250 and 5000 µg/plate in the TA 100 without metabolic activation. The precipitation of test substance was observed at 1250 and 5000 µg/plate regardless of S9 mix. In this study, Salmonella typhimurium strains TA100, TA1535, TA98 and TA1537 andEscherichia coli strain WP2uvrA were tested at six concentrations up to 1250 µg/plate with and without metabolic activation. All of the positive controls in the presence and absence of S9 mix induced marked increases in the frequency of revertant colonies. Manganese dioxide was not mutagenic in both the presence and absence of a metabolising system.

b- non-bacterial test

A different result about manganese dioxide genotoxicity compared to AMES test was reported in SIDS Dossier of MnO2 approved at SIAM 25 (17 -18 October 2007) with reference to unpublish report National Institute of Environmental Research (NIER), Korea, 2006,In vitro mammalian chromosome aberration test of manganese dioxide (Report No. G02-06035), tested by Medvill.The Chinese hamster lung cells were treated continuously (24 hours) in the absence of metabolic activation and shortly (6 hours) in the presence or absence of metabolic activation with manganese dioxide at the concentrations of 0, 217.4, 434.7, 869.4 µg/ml (limited concentration, 10 mM). In the long-term test, all concentrations significantly induced the frequency of aberrant cells. Structural chromosomal aberrations and polyploidy were not induced up to 869.4µg/ml either with or without metabolic activation in the short-term test. The numbers of structural chromosome aberration cells of positive control were significantly increased as compared with those of a negative control. Manganese dioxide showed clastogenic potential in the long-term test.

In vivo studies

The potential genotoxicity of manganese dioxide appears to be confirmed from in vivo test micronucleus assay on mice reported inSIDS Dossier of MnO2 approved at SIAM 25 (17 -18 October 2007) with reference to National Institute of Environmental Research(NIER), Korea, 2007,In vivo micronucleus test of Manganese dioxide in male ICR mice (Report No. 07-GTT-MNT-002), tested by Center for Biosafety Catholic Univ. of Daegu. 0.5% Carboxymethylcellulose and mitomycin C (0.5 mg/kg bw) were used as a negative control and positive control, respectively. Groups of 5 male mice were orally administered manganese dioxide at the dose levels of 500, 1,000, and 2,000 mg/kg bw for 24, 48 and 72 hours. All animals dosed with manganese dioxide exhibited similar PCE/(PCE + NCE) ratios compare to those of negative control animals. The MNPCE frequencies (%) of manganese dioxide (2000 mg/kg) treated animals is significantly increased (p < 0.05). All frequencies of MNPCE in negative control groups fell within acceptable ranges, while the positive control group induced clear increases in the frequencies of MNPCE.

Conclusion

Based on these results, manganese dioxide was not mutagenic in bacteria either with or without metabolic activation, but induced chromosomal aberrations in mammalian cellsin vitro. In addition, manganese dioxide did induce micronuclei in the mice bone marrow cellsin vivo. The available information suggests that manganese dioxide is genotoxic but no enough data are available to classified the substance. Moreover, MnO2 is not classified for genetic toxicity according to annex VI of CLP Regulation (EC n.1272/2008).

Short description of key information:
Available in vitro and in vivo study for genetic toxicity, some with potential concern but insufficent for classification.

Endpoint Conclusion: Adverse effect observed (positive)

Justification for classification or non-classification

Based on these results, manganese dioxide was not mutagenic in bacteria either with or without metabolic activation, but induced chromosomal aberrations in mammalian cells in vitro. In addition, manganese dioxide did induce micronuclei in the mice bone marrow cells in vivo. The available information suggests that manganese dioxide is genotoxic but no enough data are available to classified the substance.

Moreover, MnO2 is not classified for genetic toxicity according to annex VI of CLP Regulation (EC n.1272/2008).