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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Additional information

Ames test:

MMDS was evaluated for its mutagenic potential in the strains of Salmonella typhimurium, TA100, TA1535, TA98 and TA1537, and Escherichia coli WP2uvrA with or without metabolic activation. In the dose-finding assay, the highest dose was set at 5000 μg/plate, and a total of 7 doses were set with a common ratio of 4. In the dose-finding and main assays, the test substance increased the number of revertant colonies more than 2-fold compared to the negative control value in TA100, TA1535 and TA98 under the conditions of S9 (±), and the increase was dose-dependent. On the other hand, the test substance did not increase the number of revertant colonies 2-fold or more compared to the negative control value in WP2uvrA and TA1537 under the conditions of S9 (±). The positive controls induced revertant colonies more than 2-fold of the negative control value in each strain. These results indicated the assays were performed properly. Based on these results, it was concluded that MMDS was positive for mutagenicity under the test conditions of this study. The maximum mutagenic activity of the test substance was 1.30×103rev./mg (at 313 μg/plate in TA100 with S9 in the dose-finding assay). In the dose-finding and main assays, the growth inhibition of bacteria by the test substance was observed at the doses. Precipitation of the test substance was not observed at any doses.

Chromosoomaberration study:

In the first cytogenetic assay, both in the absence and presence of S9-mix, MMDS induced a statistically significant increase in the number of cells with chromosome aberrations both when gaps were included and excluded.

In the second cytogenetic assay, in the absence of S9-mix, at the 24 h continuous exposure time, MMDS did not induce a statistically significant or biologically relevant increase in the number of cells with chromosome aberrations.

In the absence of S9-mix, at the 48 h continuous exposure time, and in the presence of S9-mix at the 3 h exposure time, MMDS induced a statistically significant, dose dependent, increase in the number of cells with chromosome aberrations both when gaps were included and excluded.

It was noted that MMDS increased the number of polyploid cells both in the absence and presence of S9-mix (with the exception of the 24 h continuous exposure time). This may indicate that MMDS has the potential to disturb mitotic processes. Both in the absence and presence of S9-mix, MMDS did not increase the number of cells with endoreduplicated chromosomes.

It is concluded that this test is valid and that MMDS is clastogenic in human lymphocytes under the experimental conditions described in this report. MMDS may have the potential to disturb mitotic processes.

Mouse lymphoma assay:

In accordance with Column 1 of Annex VIII Section 8.4.3. of the REACH regulation, the study needs to be conducted if a negative result in Annex VII, section 8.4.1. and Annex VIII, section 8.4.2. is obtained. The study does not need to be conducted as the substance showed a positive result in the Ames test and a positive result in the Chromosome aberration study.

Data waiving for in vivo testing

According to Annex XI, section 1, no further studies are proposed. In vivo studies with MMDS are not considered required, since MMDS is hydrolytically unstable, and in water or in aqueous solutions MMDS will rapidly decompose in MSDA and formaldehyde. It is assumed that MMDS will decompose when it becomes bioavailable in vivo studies. Therefore, as a worst-case assumption, the genotoxic properties of formaldehyde are considered. Based on public information available (ATSDR, 1999; IARC, 2006; EFSA, 2006) formaldehyde is considered genotoxic in vivo. Formaldehyde has displayed genotoxic activity in a variety of in vivo tests with organisms ranging from bacteria to rodents. The weight of evidence incidate that formaldehyde itself is capable of directly reacting with DNA, and producing genotoxic effects, especially when metabolic capacities are exceeded (ATSDR, 1999). IARC reports in 2006, that there is evidence that formaldehyde is genotoxic in multiple in-vitro models and in exposed humans and laboratory animals. Studies in humans revealed increased DNA–protein crosslinks in workers exposed to formaldehyde. This is consistent with laboratory studies, in which inhaled formaldehyde reproducibly caused DNA–protein cross-links in rat and monkey nasal mucosa.

EFSA (2006) reports the following: Most available in vivo genotoxicity studies dealing with formaldehyde focus on “local and/or systemic genotoxicity” animal models with exposure by inhalation. Examination of results and of the experimental conditions in more than 40 published in vivo genotoxicity studies indicates that any genotoxic potential of formaldehyde is localised to the immediate site of contact and is not expressed systemically in experimental animals. In human studies, local and systemic genotoxicity of formaldehyde is difficult to assess mainly because all human studies available considered inhalation exposure to formaldehyde and suffer from lack of description on levels of exposure and lack of information on co-exposures and other confounders.

Overall it can be concluded that formaldehyde is considered genotoxic in vivo at the site of contact. This conclusion is also considered applicable for MMDS.


Short description of key information:
MMDS was evaluated for its mutagenic potential in the strains of Salmonella typhimurium, TA100, TA1535, TA98 and TA1537, and Escherichia coli WP2uvrA with or without metabolic activation according to OECD Guideline 471 and GLP principles.
A chromosome aberration study with MMDS was performed according to OECD 473 guideline and GLP principles, in cultured peripheral human lymphocytes in two independent experiments.
In vivo genotoxicity was waived, based on public information available for formaldehyde, one of the decomposition products of MMDS.

Endpoint Conclusion: Adverse effect observed (positive)

Justification for classification or non-classification

Based on the results of the Ames study it is concluded that MMDS is mutagenic in Salmonella typhimurium strains with and without metabolic activation in the reverse mutation assay using Salmonella typhimurium and Escherichia coli.

Based on the results of the chromosome aberration study, it is concluded that MMDS is clastogenic in human lymphocytes both in the absence and presence of S9 -mix. MMDS may have the potential to disturb mitotic processes.

The test substance should be classified as a Category 2 mutagen and have the hazard statement H341: Suspected of causing genetic defects with it, in accordance with Regulation EC No. 1272/2008 and according to Directive 67/548/EEC, the test substance should be classified as a Mutagens (Xn) and have the risk phrase R68: Possible risk of irreversible effects associated with it.