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Additional information

Based on the results of three reliable (all three studies Klimisch score: 1) in vitro studies (Ames test according to OECD 471, HPRT test according to OECD 476 and Micronucleus test according to OECD 487), Ethyltriglycol methacrylate shows no potential to induce gene mutations in bacterial cells nor does it induce chromosomal aberrations in cultured human lymphocytes.

Bacterial reverse mutation assay

In a reverse gene mutation assay in bacteria according to OECD guideline 471 Salmonella typhimurium TA98, TA100, TA1535, TA1537 and TA102 strains were exposed to Ethyltriglycol methacrylate at concentrations up to 5000 µg/plate in the presence and absence of mammalian metabolic activation.

In two independent experiments Ethyltriglycol methacrylate was investigated for its potential to induce gene mutations according to the plate incorporation test (experiment I) and the pre-incubation test (experiment II).

No precipitation of Ethyltriglycol methacrylate was observed in any tester strain used in experiment I and II (+/- S9 metabolic activation).

 

No toxic effects occurred in the test groups with and without metabolic activation in both independent experiments. The reduction in the number of revertants down to a mutation factor of 0.5 found in experiment I in tester strain TA 1537 at a concentration of 2500 µg/plate (without metabolic activation) was regarded as not biologically relevant due to lack of a dose-reponse relationship.

The plates incubated with the test article showed normal background growth up to 5000 µg/plate with and without S9-mix in all strains used.

The positive controls induced the appropriate responses in the corresponding strains. There was no evidence of induced mutant colonies over background.

Under the conditions of this study according to OECD 471, the test substance, Ethyltriglycol methacrylate

(ET3EGMA; CAS: 39670 -09 -2), did not show any mutagenic activity in the bacterial reverse mutation test with Salmonella typhimurium. (BSL, 2011)

 

In vitro Micronucleus Test

In a mammalian cell micronucleus assay according to OECD guideline 487 (adopted July 22, 2010), primary human lymphocyte cultures were exposed to Ethytriglycol methacrylate (98.95%) in deionised water with and without metabolic activation (S9 mix).

The following concentrations were evaluated (dose calculations adjusted to purity):

Experiment

I:

4 h treatment without metabolic activation: 16.1 -2486 µg/ml

4 h treatment with metabolic activation: 16.1 -2486 µg/ml

 

Experiment IIA:

20 h treatment without metabolic activation: 49.5 – 2486 µg/mL

4 h treatment with metabolic activation: 151.5 – 2486 µg/mL

 

Experiment IIB:

20 h treatment without metabolic activation: 75 – 2400 µg/mL

 

Ethytriglycol methacrylate was tested up to cytotoxic or the guideline limit concentration of 10 mM (corresponding to 2486.0 mg/mL). Cytotoxic effects were observed after 4 h treatment with 2486 µg/ml in the absence of S9 mix; no cytotoxicity was observed in the presence of S9 mix up to 2486 µg/ml.

In the absence and presence of S9 mix no biologically relevant increase in the number of cells carrying micronuclei was observed after treatment with the test item.

 

The micronucleus rates of the cells after treatment with the test item (0.05 - 0.95 % micronucleated cells) were within the range of the solvent control values (0.35 -1.05 % micronucleated cells) and within the range of the laboratory historical control data. Positive controls induced the appropriate response.

Ethyltriglycol methacrylate did not induce micronuclei in human lymphocytes in vitro, when tested up to cytotoxic or the highest required/evaluable concentration. Therefore, Ethytriglycol methacrylate is considered to be non-clastogenic in this in vitro micronucleus test, when tested up to cytotoxic or the highest evaluable concentration. (Harlan, 2012)

 

Mammalian cell chromosome aberration assay

In a mammalian cell gene mutation assay according to OECD guideline 476, adopted 21 July 1997 (HPRT test), V79 cells cultured in vitro were exposed to Ethyltriglycol methacrylate (98.95% a.i.) at the following concentrations in the presence and absence of mammalian metabolic activation (S9 mix).

Experiment I:

Without metabolic activation: 0 (control), 246, 492, 984, 1476, 1968, 2460 µg/ml

With metabolic activation: 0 (control), 246, 492, 984, 1476, 1968, 2460 µg/ml

 

Experiment II:

Without metabolic activation: 0 (control), 246, 492, 984, 1476, 1968, 2460 µg/ml

With metabolic activation: 0 (control), 246, 492, 984, 1476, 1968, 2460 µg/ml

In both main experiments the cultures at the lowest concentration with and without metabolic activation (246 µg/mL) were not continued since a minimum of only four analysable concentrations is required by the guidelines.

 

Ethyltriglycol methacrylate was tested up to cytotoxic concentrations. The positive controls induced the appropriate response. There was no evidence of induced mutant colonies over background.

In this HPRT test, Ethyltriglycol methacrylate was found to be not mutagenic.

Based on the available data, Ethyltriglycol methacrylate is not genotoxic. There are no data gaps for the endpoint genotoxicity. No human information is available for this endpoint. However, there is no reason to believe that these results would not be applicable to humans. (Harlan, 2012)


Short description of key information:
Based on the results of three reliable in vitro studies (Ames test according to OECD 471, HPRT test according to OECD 476 and Micronucleus test according to OECD 487), Ethyltriglycol methacrylate shows no potential to induce gene mutations in bacterial cells nor does it induce chromosomal aberrations in cultured human lymphocytes.
- not mutagenic in the Salmonella typhimurium reverse mutation assay (OECD guideline 471; GLP, BSL, 2011)
- not mutagenic in the mammalian cell gene mutation assay (OECD guideline 476; HPRT test, V79 cells; GLP, Harlan, 2012)
- negative in an in vitro micronucleus test (OECD guideline 487; Primary human lymphocytes,GLP, Harlan, 2012)

There were no in vivo genetic toxicity studies identified for Ethyltriglycol methacrylate.
No single key study has been selected, since all available studies were negative.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the results of three reliable in vitro studies (Ames test according to OECD 471, HPRT test according to OECD 476 and Micronucleus test according to OECD 487), Ethyltriglycol methacrylate shows no potential to induce gene mutations in bacterial cells nor does it induce chromosomal aberrations in cultured human lymphocytes.

The available data do confirm the non-mutagenicity of the substance. Therefore, no classification is required.