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Administrative data

Key value for chemical safety assessment

Additional information

Data availability: For MAA a bacterial mutation test is available. For all other required endpoints data from MMA are used by read-across.

in vitro

Gene mutation in bacteria

In a standardised bacterial mutation test according to NTP protocol, methacrylic acid was not mutagenic in S. typhimurium strains TA97, TA98, TA100, TA1535 and TA 1537 with and without metabolic activation (Zeiger et al. 1987). Additionally, the esters of the category have been tested over a relevant dose range in the Salmonella reverse mutation test (Ames test) with and without metabolic activation by S9-mix. In no study was there an indication of a mutagenic effect.

Gene mutation in mammalian cells

There are no gene mutation studies available in mammalian cells. The EU ESR for MAA (2002) concluded "Further testing on methacrylic acid is lacking. However, taking into consideration the data on the structurally related substance methyl methacrylate - which indicate that this substance does not express a genotoxic potential in vivo - there is no need for further testing." Supporting evidence can be drawn by category read-across from a negative gene mutation test with EHMA (Harlan, 2009). Although the dominant lethal assay of Anderson (1976) and micronucleus assay of Hachiya (1982) with MMA are strictly speaking not gene mutation assays, the absence of positive findings is also supporting the absence of concern for genotoxicity of MAA.

Cytogenicity in mammalian cells

In vitro

MAA, by analogy to MMA, has the potential for induction of mutagenic effects, esp. clastogenicity; however, this potential seems to be limited to high doses with strong toxic effects.

In vivo

Because the in vitro data are therefore somewhat ambiguous the in-vivo study data are used by read-across. Quote from the MMA ESR (ECB, 2002): “Two chromosomal aberration tests were conducted by Anderson et al. (1976, 1979) investigating the effect of inhalation exposure to methyl methacrylate for doses ranging from ca. 0.4 to 36.5 mg/L (100 to 9000 ppm). In both tests acute exposure was for 2 h (sampling 24 h after treatment) and subacute exposure for 5 h a day on 5 consecutive days (sampling 24 h after last treatment). Data on toxicity were not given. Group sizes varied from 2 to 9; as far as possible 50 metaphases were analysed per animal. The first study was negative for chromosomal aberration frequencies when - as usual - gaps were excluded. Including gaps and combining two acute experiments conducted independently some increases in aberration frequency were statistically significant. ” This is also due to a particularly low control rate in this experimental segment. Compared to other, almost twofold higher control values in other segments of the report, this finding appears to be of little biological importance. Further from the MMA ESR (ECB, 2002): “In the second study frequencies of chromosomal aberrations excluding gaps were not given. Including gaps increases were recorded at some experimental entries. Furthermore, combined data on chromosomal aberration frequencies exclusively gaps from both studies were given, then weak increases were obtained for 400 and 700 ppm in the acute study (not for 100, 1,000 or 9,000 ppm) and 9,000 ppm in the subacute study. Both studies suffer from inadequate description; esp. the second study demonstrates severe methodological problems, e. g., analysis of 50 metaphases was not possible for 10 out of 27 animals in the acute and 10 out 26 in the subacute test. Altogether, a clear conclusion cannot be drawn from theses studies.

Hachiya et al. (1982) reported on a negative bone marrow micronucleus assay with mice. In an acute test methyl methacrylate was given by gavage in doses ranging from 1,130 to 4,520 mg/kg, in a subacute assay daily doses of 1,130 mg/kg were given on 4 consecutive days. All groups consisted of 6 animals; sampling was done 24 h after (last) administration. There was no increase in the frequency of micronucleated polychromatic erythrocytes. The percentage of reticulocytes from all bone marrow cells was not affected data on general toxicity were not given. ”

MAA ESR concluded In vitro MMA has the potential for induction of mutagenic effects, esp. clastogenicity; however, this potential seems to be limited to high doses with strong toxic effects. Furthermore, the negative in vivo micronucleus test - and to some extent the negative dominant lethal assay - indicates that this potential is probably not expressed in vivo.” 

Overall, it may be concluded from mammalian cell culture assays with methyl methacrylate that MAA has the potential to be is a high-toxicity clastogen (i. e. induction of chromosomal aberrations is bound to highly toxic doses). Therefore the in vivo data for MMA are used to finally assess the genotoxic potential.The weight of evidence approach indicates that MMA is not mutagenic. MAA, having a reduced reactivity at the double bond compared to MMA, is not expected to be mutagenic.


Short description of key information:
Gene mutation in bacteria
S. typhimurium TA97, TA98, TA100, TA1535, with and without metabolic activation: negative (NTP method, Haworth et al. 1983)
Gene mutation in mammalian cells
The EU ESR for MAA (2002) concluded "Further testing on methacrylic acid is lacking. However, taking into consideration the data on the structurally related substance methyl methacrylate - which indicate that this substance does not express a genotoxic potential in vivo - there is no need for further testing."
Cytogenicity in mammalian cells
see in vivo data
Dominant lethal assay, mouse: negative (Anderson and Hodge, 1996)
Chromosome aberration assay, rat: negative/inconclusive (Anderson et al., 1976, 1979)
Micronucleus assay, mouse: negative (Hachiya et al. 1982)

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Methacrylic acid was negative in a bacterial gene mutation test. Additional information is gained by read-across from methyl methacrylate. From mammalian cell culture assays it may be concluded that methyl methacrylate is a high toxicity clastogen (i. e. induction of chromosomal aberrations is bound to highly toxic doses). The effect is not dependent on presence of S-9 mix. In vivo an oral mouse bone marrow micronucleus test was negative for doses up to 4,520 mg/kg bw. No clear conclusion could be drawn from bone marrow chromosomal aberration assays with rats. A dominant lethal assay with male mice led to a negative result. In vitro MMA has the potential for induction of mutagenic effects, esp. clastogenicity; however, this potential seems to be limited to high doses with strong toxic effects. Furthermore, the negative in vivo micronucleus test and the negative dominant lethal assay indicate that this potential is probably not expressed in vivo.

The absence of the ester group in MAA reduces the reactivity of the double bond in comparison to the esters.

Therefore, methacrylic acid has not to be classified for its mutagenic potential according to CLP (1272/2008/EEC) and UN-GHS requirements.