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Administrative data

Key value for chemical safety assessment

Additional information

There is a sufficient number of negative mutagenicity tests available for structurally related hydroxyl- and ether methacrylates within the category of hydroxyl- and ether methacrylates.

Negative Ames-tests are available for BDGMA itself and for 2-Hydroxyethyl methacrylate (HEMA), Hydroxypropyl methacrylate (HPMA), 2-Ethoxyethyl methacrylate (ETMA) and Ethyltriglycol methacrylate (ET3EGMA).

Negative gene mutation tests (HPRT assays) exist for HEMA, HPMA and ET3EGMA. Concerning chromosome mutation data, chromosome aberration tests are positive for HEMA and HPMA, but there exists a negative in vitro micronucleus assays for ET3EGMA. The former positive in vitro findings in the chromosome aberration tests are not unusual for low molecular weight methacrylates as HEMA and HPMA. However, lack of relevance to the organism was demonstrated for the substances by negative micronucleus tests in vivo.

 

In conclusion, all category members including BDGMA can be considered as not genotoxic. Further mutagenicity studies to be performed with BDGMA are not necessary.

 

The reverse mutation assay with BDGMA together with HPRT test and micronucleus test in vivo with the structurally analogue ET3EGMA were selected as key studies and are described in more detail below.

 

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 Butyldiglycol methacrylate in DMSO at concentrations up to 5000 µg/plate in the presence and absence of mammalian metabolic activation. The test was performed as pre-incubation test with 1 hour pre-incubation. The positive controls induced the appropriate responses in the corresponding strains. There was no evidence of induced mutant colonies over background.

 

In vitro Micronucleus Test

No study is available with BDGMA but a study with the structural related substance Ethyltriglcol methacrylate.

 

In a mammalian cell micronucleus assay according to OECD guideline 487 (adopted July 22, 2010), primary human lymphocyte cultures were exposed to Ethyltriglycol 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

 

Ethyltriglycol 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.

 

Mammalian cell chromosome aberration assay

No study is available with BDGMA but a study with the structurally related substance Ethyltriglcol methacrylate.

 

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 /L

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

 

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 information, BDGMA 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.


Justification for selection of genetic toxicity endpoint
No single key study has been selected, since all available studies were negative

Short description of key information:
BDGMA considered to be not genotoxic:
- not mutagenic in the Salmonella typhimurium reverse mutation assay (OECD guideline 471; GLP)
- not mutagenic in the mammalian cell gene mutation assay (OECD guideline 476; HPRT test, V79 cells; GLP; test performed with analogeous substance Ethyltriglycol methacrylate)
- negative in an in vitro micronucleus test (OECD guideline 487; Primary human lymphocytes,GLP)
Further evidence for lack of genotoxicity by read-across to 2-Hydroxyethyl methacrylate (HEMA), Hydroxypropyl methacrylate (HPMA), 2-Ethoxyethyl methacrylate (ETMA).

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the reliable available data, Butyldiglycol methacrylat does not need to be classified for mutagenicity according to the criteria given in regulation (EC) 1272/2008 or the former European directive on classification and labelling 67/548/EEC. Thus, no labelling is required.