2-Propenoic acid, 2-methyl-, C13-15-branched and linear alkyl esters

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Ames-Test: negative

Additional information

For 2-Propenoic acid, 2-methyl-, C13-C15-branched and linear alkyl esters only an in vitro bacterial toxicity test is available. But for the read-across substances 2-Propylheptyl methacrylate (CAS 149855-64-1), C17-Methacrylate (CAS 1473386-29-6) and Isodecyl methacrylate (CAS 29964-84-9) more data are avialable:

in vitro bacterial toxicity

The test substance 2-Propenoic acid, 2-methyl-, C13-15-branched and linear alkyl esters was tested for its mutagenic potential based on the ability to induce point mutations in selected loci of several bacterial strains, i.e. Salmonella typhimurium and Escherichia coli, in a reverse mutation assay. Test strains are TA 1535, TA 100, TA 1537, TA 98 and E. coli WP2 uvrA, dosed in the range of 33 μg - 5000 μg/plate (SPT) and 33 μg - 5000 μg/plate (PIT). Standard plate test (SPT) and preincubation test (PIT) both with and without external metabolic activation (liver S9 mix from rats treated with enzyme inducers). Precipitation of the test substance was observed at and above 1000 μg/plate with and without S9 mix. A bacteriotoxic effect only was observed in the preincubation test depending on the strain and test conditions at and above 2500 μg/plate. A relevant increase in the number of his+ or trp+ revertants (increased by a factor of 2 or above compared to the concurrent control for Salmonella typhimurium TA 100, TA 98 and Escherichia coli WP2 uvrA, or a factor of 3 or above for Salmonella typhimurium TA 1535 and TA 1537) was not observed in the standard plate test or in the preincubation test with or without the addition of an external metabolizing system (liver S9 mix of rats treated with enzyme inducers). The test substance 2-Propenoic acid, 2 -methyl-, C13-15-branched and linear alkyl esters is not mutagenic in the Salmonella typhimurium/Escherichia coli reverse mutation assay in the absence and the presence of external metabolic activation (BASF SE, 2021).

In vitro chromosomal aberration assay on mammalian cells

The test substance 2-Propylheptyl methacrylate was assessed for its potential to induce micronuclei in V79 cells in vitro (clastogenic or aneugenic activity) (OECD 487). Two independent experiments were carried out, both with and without the addition of liver S9 mix from induced rats (exogenous metabolic activation). 1st Experiment 4 hours exposure; 24 hours harvest time; without S9 mix: 0; 3.13; 6.25; 12.50; 25.00; 50.00; 100.00 μg/mL 4 hours exposure, 24 hours harvest time, with S9 mix: 0; 6.25; 12.50; 25.00; 50.00; 100.00; 200.00 μg/mL 2nd Experiment 24 hours exposure, 24 hours harvest time, without S9 mix 0; 1.56; 3.13; 6.25; 12.50; 25.00; 50.00 μg/mL 4 hours exposure, 44 hours harvest time, with S9 mix 0; 6.25; 12.50; 25.00; 50.00; 100.00; 200.00 μg/mL. In this study, cytotoxicity indicated by clearly reduced cell count was observed at the highest applied test substance concentrations in all experimental parts without S9 mix. In the presence of metabolic activation, no cytotoxicity was observed in the pretest. Therefore, dose selection for the main experiments was based on the solubility properties of the test substance. No cytotoxicity was obtained when tested up to clearly precipitating concentrations. On the basis of the results of the present study, the test substance did not cause any biologically relevant increase in the number of cells containing micronuclei either without S9 mix or after adding a metabolizing system. The dose-dependencies observed in both parts of the 1st Experiment have to be considered as biologically irrelevant.

Based on this result 2-Propylheptyl methacrylate is considered not to have a chromosome-damaging (clastogenic) effect nor to induce numerical chromosomal aberrations (aneugenic activity) under in vitro conditions in V79 cells in the absence and the presence of metabolic activation (BASF SE, 2014).

 

The test substance C 17 Methacrylate was assessed for its potential to induce micronuclei in V79 cells in vitro (clastogenic or aneugenic activity) (OECD 487). Two independent experiments were carried out, both with and without the addition of liver S9 mix from induced rats (exogenous metabolic activation). 1st Experiment 4 hours exposure, 24 hours harvest time, without S9 mix: 0; 6.25; 12.50; 25.00; 50.00; 100.00; 200.00μg/mL 4 hours exposure, 24 hours harvest time, with S9 mix: 0; 6.25; 12.50; 25.00; 50.00; 100.00; 200.00μg/mL. 2nd Experiment 24 hours exposure, 24 hours harvest time, without S9 mix 0; 12.50; 25.00; 50.00; 100.00; 200.00μg/mL 4 hours exposure, 44 hours harvest time, with S9 mix 0; 12.50; 25.00; 50.00; 100.00; 200.00μg/mL. The vehicle controls gave frequencies of micronucleated cells within our historical negative control data range for V79 cells. Both positive control substances, EMS and cyclophosphamide, led to the expected increase in the number of cells containing micronuclei. The test substance was poorly soluble in culture medium. In this study in the absence and the presence of metabolic activation no cytotoxicity indicated by reduced cell count or proliferation index (CBPI) was observed up to the highest applied test substance concentration. Therefore, concentrations at the border of test substance solubility in culture medium were investigated for cytogenetic damage. On the basis of the results of the present study, the test substance did not cause any biologically relevant increase in the number of cells containing micronuclei either without S9 mix or after adding a metabolizing system. Thus, under the experimental conditions described, C 17 Methacrylate is considered not to have a chromosome-damaging (clastogenic) effect nor to induce numerical chromosomal aberrations (aneugenic activity) under in vitro conditions in V79 cells in the absence and the presence of metabolic activation. (BASF SE, 2015)

 

In vitro gene mutation assay in mammalian cells (for justification see read-across document)

Isodecyl methacrylate (CAS No. 29964-84-9) was assessed for its potential to induce gene mutations at the HPRT locus using V79 cells of the Chinese hamster. The assay was performed in two independent experiments with identical experimental procedures, using two parallel cultures each. The first main experiment was performed with and without liver microsomal activation and a treatment period of 4 h. The second experiment was performed with a treatment period of 24 hours in the absence of metabolic activation and 4 hours in the presence of metabolic activation. The cell cultures were evaluated at the following concentrations: Experiment I: without S9 mix:  0.1; 0.3; 0.5; 1.0; and 2.0 µg/mL and with S9 mix: 37.5; 75; 150; 300; and 1200 µg/mL. Experiment II: without S9 mix: 18.8 ;37.5; 75.0; 150; and 600 µg/mL and with S9 mix: 37.5; 75.0; 150; 300; and 600 µg/mL. Relevant toxic effects indicated by a relative cloning efficiency 1 below 50 % occurred at 1.0 µg/mL and above in the first experiment without metabolic activation and at 1200.0 µg/mL and above with metabolic activation. In the second experiment toxic effects as described above occurred at 37.5 µg/mL without metabolic activation and at 1200 µg/mL with metabolic activation. No relevant and reproducible increase in mutant colony numbers/1E6cells was observed in the main experiments up to the maximum concentration. In both experiments of this study (with and without S9 mix) the range of the solvent controls was from 5.7 up to 24.0 mutants per 1E6cells; the range of the groups treated with the test item was from 3.3 up to 34.1 mutants per 106cells. EMS(150 µg/mL in experiment I and 75 µg/mL in experiment II) and DMBA (2.0 µg/mL) were used as positive controls and showed a distinct increase in induced mutant colonies. This showed the sensitivity of the test system and the activity of the S9 mix. In conclusion it can be stated that under the experimental conditions reported the test item did not induce gene mutations at the HPRT locus in V79 cells (Evonik Rohm, 2008).

 

Justification for classification or non-classification

Based on the results, the test item was not classified and labelled accordingto Regulation (EC) No 1272/2008 (CLP).