Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

Potassium permanganate has been used as a surrogate for sodium permanganate where data are not available. Read-across from potassium permanganate to sodium permanganate is appropriate from the toxicological point of view as the most toxicologically relevant part of the substances is the same (permanganate). The contribution of the sodium/potassium ions to the toxicity of the respective substances is likely to be minimal. The toxicity of both substances is therefore likely to be very similar and will be dominated by local (site of contact) irritant/corrosive effects and systemic toxicity due to the absorption of manganese ions. This toxicophore similarity is adequate justification for waiving the conduct of specific studies with sodium permanganate and the dossier reflects this waiving proposal by including summaries of read-across studies where appropriate.

No evidence of mutagenicity was seen in a guideline-compliant Ames test with the read-across substance potassium permanagate (Taublova, 2006). No evidence of clastogenicity was seen in a guideline-compliant rat bone marrow micronucleus assay with potassium permangate (Plodikova, 2006). Further studies of genetic toxicity with permanganate are not proposed. The substance is a reactive oxidant and under physiological conditions will react rapidly with organic material and will be reduced to manganese (II) and other forms of manganese. Read-across to other forms of manganese is therefore appropriate. Some review information related to forms of manganese have been included as supporting information.

NTP studies with manganese (II) sulphate

Manganese (II) sulphate monohydrate (100 to 10000 μg/plate), tested in two laboratories, was not mutagenic in S. typhimurium strains TA97, TA98, TA100, TA1535, or TA1537. All tests were performed with a pre-incubation protocol, with and without Aroclor 1254-induced male Sprague-Dawley rat or Syrian hamster liver S9. In cytogenetic tests with CHO cells, manganese (II) sulphate monohydrate induced SCEs with and without S9 activation. Two of the three positive responses obtained in the absence of S9 required delayed cell culture harvest to offset severe cytotoxicity; with S9, all positive responses were achieved with normal harvest times. Manganese (II) sulphate monohydrate also induced chromosomal aberrations in CHO cells in the absence of S9; as with the SCE test, the harvest time was extended to allow sufficient cells to accumulate for analysis. Increases in the percentage of cells with aberrations were not well correlated with the dose of manganese (II) sulfate monohydrate and occurred within a rather limited range (176 to 300 μg/mL). In the presence of S9, no significant increase in chromosomal aberrations was observed. Manganese (II) sulfate monohydrate did not induce SLRL mutations in germ cells of adult male D. melanogaster treated with 12,500 ppm in feed or 1,000 ppm administered by injection.

A number of other studies investigating the genetic toxicity of manganese compounds are reviewed by the US ATSDR (2008).

ATSDR review

The review concludes that in vitro mutagenicity studies in both bacteria and mammalian strains are conflicting. While manganese sulphate was shown to not be mutagenic to Salmonella typhimurium strains TA97, TA98, TA100, TA1535, or TA1537 either in the presence or absence of S9 from Aroclor 1254-induced liver from rats or Syrian hamsters, it was shown to be mutagenic to strain TA97 elsewhere. In yeast (Saccharomyces cerevisiaestrain D7), a fungal gene conversion/reverse mutation assay indicated that manganese sulphate was mutagenic (Singh 1984). Manganese chloride was reportedly not mutagenic in S. typhimurium strains TA98, TA100, and TA1535, but it was mutagenic in strain TA1537, and conflicting results were obtained for TA102.In vitroassays in mammalian cells also gave conflicting results concerning manganese mutagenicity. Manganese chloride produced gene mutations in cultured mouse lymphoma cells. Manganese chloride caused DNA damagein vitrousing human lymphocytes at a concentration of 25 μm without metabolic activation, but not at the lower tested concentrations of 15 and 20 μm. The compound also caused DNA damage in human lymphocytes using the single-cell gel assay technique in the absence of metabolic activation, but caused no DNA damage when S9 was present. Manganese sulphate induced sister chromatic exchange in Chinese hamster ovary (CHO) cells in both the presence and absence of S9 from Aroclor 1254-induced rat liver. In a separate assay, manganese sulphate also induced chromosomal aberrations in CHO cells in the absence of S9 but not in its presence. Manganese chloride caused chromosome aberrations in human lymphocytes without metabolic activation, but only when treated in the G2 phase of the cell cycle; treatment in the G1, G1/S, and S1 phases of the cell cycle did not result in chromosome aberrations. The compound was also found to be clastogenic in root tip cells ofVicia faba,but not in cultured FM3A cells in the absence of metabolic activation. Potassium permanganate caused chromosomal aberrations in FM3A cells, but not in a primary culture of cells from Syrian hamster embryos when tested in the absence of metabolic activation. Manganese chloride caused cell transformation in Syrian hamster embryo cells.

In vivo, manganese chloride did not produce somatic mutations in Drosophila melanogaster fruit flies in one study, and manganese sulfate did not induce sex-linked recessive lethal mutations in germ cells of male D. melanogaster. In vivoassays in mice showed that oral doses of manganese sulphate or potassium permanganate caused micronuclei and chromosomal aberrations in bone marrow. In contrast, oral doses of manganese chloride did not cause chromosomal aberrations in the bone marrow or spermatogonia of rats.


Short description of key information:
No evidence of mutagenicity was seen in an Ames test: no evidence of clastogenicity was seen in a micronucleus assay with the read-across substance potassium permanganate.

Potassium permanganate has been used as a surrogate for sodium permanganate where data are not available. Read-across from potassium permanganate to sodium permanganate is appropriate from the toxicological point of view as the most toxicologically relevant part of the substances is the same (permanganate). The contribution of the sodium/potassium ions to the toxicity of the respective substances is likely to be minimal. The toxicity of both substances is therefore likely to be very similar and will be dominated by local (site of contact) irritant/corrosive effects and systemic toxicity due to the absorption of manganese ions. This toxicophore similarity is adequate justification for waiving the conduct of specific studies with sodium permanganate and the dossier reflects this waiving proposal by including summaries of read-across studies where appropriate.

Endpoint Conclusion:

Justification for classification or non-classification

The data on genotoxicity of managanese compounds are conflicting, as is common for metal species. However it is noted that manganese (II) was not found to be carcinogenic in high quality studies in two species.