Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

Registered substance:

The registered substance was found negative in a recent GLP bacterial reverse mutation test according to OECD guideline 471 and in an in vitro gene mutation test according to OECD guideline 476. The registered substance dissociates in water into zinc compounds and methacrylic acid. Also, the results found on the substance are in line with the numerous genotoxicity studies available on zinc compounds and methacrylic acid/methyl methacrylate (negative in Ames test and in mutagenicity in mammalian cells tests). Therefore the global genotoxic potential of the registered substance was infered from the data available on soluble zinc compounds and methacrylic acid/methyl methacrylate.

Zinc compounds (zinc sulphate):

Conflicting information was found on zinc compounds for their potential of clastogenicity in mammalian cell systems. Positive as well as negative results were obtained in these cell systems. In those studies where chromosomal aberrations or sister chromatide exchange were observed, these were generally considered to be weak and occurred only at high, often cytotoxic concentrations. Moreover, these positive in vitro findings have also to be seen in context of the impact that changes in zinc levels can have on cell system processes that are controlled by a strict metal homeostasis. A change of this metal homeostasis due to increased zinc levels, may lead to a binding of zinc to amino acids like cystein and therefore to an inhibition of certain enzymes. This can lead to interactions with the energy metabolism, signal transmission and apoptotic processes which can lead to the observed clastogenic or aneugenic effects in in vitro systems (EU RAR, 2004)

Methacrylic acid/methyl methacrylate:

Methacrylic acid genotoxic properties were deduced from methyl methacrylate data. In vitro methyl methacrylate has the potential for induction of mutagenic effects, especially clastogenicity; however, this potential seems to be limited to high doses with strong toxic effects. Furthermore, negative in vivo tests indicate that this potential is not expressed in vivo (EU RAR, 2002). The mutagenicity of methacrylate compounds has been reviewed by Johannssen et al., 2008: while methacrylate chemical class produced a consistently positive response when tested in the mouse lymphoma assay and/or other in vitro mammalian cell tests assessing clastogenicity, no evidence of point mutations was observed in Salmonella bacterial tests or in hprt mutation tests in mammalian cells, and no evidence of a mutagenic effect was seen in in vivo chromosomal aberration and micronucleus studies.

EU RAR (2002) Methyl methacrylate. Risk assessment report, 1st priority list, Volume 22, European Commission, Institute for Health and Consumer Protection, European Chemicals Bureau.

EU RAR (2004) Zinc sulphate. Risk assessment report, 2nd priority list, Volume 46, European Commission, Institute for Health and Consumer Protection, European Chemicals Bureau.


Justification for selection of genetic toxicity endpoint
No study was selected because more than one study is used to assess the genotoxicity of the registered substance.

Short description of key information:
The registered substance was found negative in bacterial reverse mutation test and in gene mutation test in mammalian cells. When analysing data available on soluble zinc compounds and methacrylic acid/methyl methacrylate, many studies show ambiguous or positive responses in in vitro tests assessing clastogenicity, but overall negative response in in vivo tests.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The basic assumption to deduce the toxicological properties of the registered substance (based on its behaviour in water) is that after intake of the substance, it is mainly transformed into the ionic species and zinc compounds and the methacrylic part of the substance are the determining factors of the biological activities of the registered substance.

This assumption is confirmed by the genotoxicity studies performed on the registered substance where negative reponse was found in Ames test and in an in vitro gene mutation in mammalian cells test. These results are in line with the numerous studies performed on both zinc compounds and methacrylate compounds. Therefore the genotoxic potential of the registered substance was deduced from all the data available on these compounds. The overall weight of evidence from the existing in vitro and in vivo genotoxicity assays suggest that zinc compounds and methacrylate compounds do not have biologically relevant genotoxic activity, which was confirmed by other regulatory reviews of the genotoxicity of zinc compounds and methacrylate compounds.

Thus the registered substance does not need to be classified for genotoxicity under the Directive 67/548/EEC and the CLP Regulation (EC) No 1272/2008.