1-(2-hydroxyethyl)imidazolidin-2-one

Endpoint summary

Additional information

1-(2-hydroxyethyl) imidazolidin-2-one was tested for mutagenicity in the Ames test (Salmonella strains TA1535, TA100, TA1537, TA98) and in the Escherichia coli - reverse mutation assay (Escherichia coli WP2 uvrA) both in the standard plate test and in the preincubation test with and without the addition of a metabolizing system at concentrations of 20, 100, 500, 2500 and 5000 µg/plate (vehicle: water) according to OECD guideline 471 and 472 and under GLP (BASF AG, 1997). An increase in the number of his+ or trp+ revertants was not observed both in the standard plate test and in the preincubation test either without S-9 mix or after the addition of a metabolizing system. No bacteriotoxic effect (reduced his- or trp- background growth, decrease in the number of his+ or trp+ revertants) was observed. No test substance precipitation was found.

According to the results of the present study, the test substance is not mutagenic in the Ames test and in the Escherichia coli - reverse mutation assay under the experimental conditions chosen here.

 

In a second study, 1-(2-hydroxyethyl) imidazolidin-2-one was tested in the Salmonella typhimurium reverse mutation assay with Salmonella typhimurium strainsTA1535, TA1537, TA100 and TA98 in a GLP compliant OECD guideline 471 (Akzo Nobel/NOTOX, 1995) The test substance was tested up to and including concentrations of 100, 333, 1000, 3330 and 5000 µg/plate (vehicle: water)in the absence and presence of S9-mix. The test substance did not induce a dose-related increase in the number of revertant colonies in the absence or in the presence of S9-mix, in two independently repeated experiments.The substance did not precipitate in the top agar. Precipitation of the substance on the plates was not observed at the start or at the end of the incubation period in all tester strains. The bacterial background lawn was not reduced at all concentrations tested and no decrease in the number of revertants was observed.

Based on the results of this study it is concluded that 1-(2-hydroxyethyl) imidazolidin-2-one is not mutagenic in the Salmonella typhimurium reverse mutation assay.

 

Furthermore, the mutagenicity of 1-(2-hydroxyethyl) imidazolidin-2-one was investigated by the preincubation method, using Salmonella typhimurium TA100, TA1535, TA98, and TA1537 and E. coli WP2 uvrA, with and without S9 mix in a GLP study according to OECD guideline 471 at concentrations of 313, 625, 1250, 2500 and 5000 µg/plate (Rohm and Haas, 1995).

At all of the set concentrations, the numbers of reverse mutation colonies were less than twice those of the negative control for all of the test strains. Furthermore, the numbers of negative control and positive control reverse mutation colonies were observed to be within the ranges of the background data of the laboratory. From these results, it was judged that 1-(2-hydroxyethyl) imidazolidin-2-one does not have any reverse mutation induction properties under the conditions of this trial.

 

Furthermore, two older Ames tests are available which were performed to a protocol comparable to OECD guideline 471 (Rohm and Haas, 1983 and Litton Bionetics Inc., 1976). The results of these studies confirm the negative results that were observed in the three more recent available studies as described above.

 

As no HPRT test is available with 1-(2-hydroxyethyl) imidazolidin-2-one, read-across with the structural analogue 2-imidazolidone is applied.

A GLP study was performed to investigate the potential of the test substance to induce gene mutations at the HPRT locus in V79 cells of the Chinese hamster, according to OECD 476, (BASF SE/Harlan, 2012).

The assay was performed in two independent experiments, using two parallel cultures each. The first main experiment was performed with and without liver microsomal activation and a treatment period of 4 hours.The second experiment was performed with a treatment time of 4 hours with and 24 hours without metabolic activation.

The highest concentration of the pre-experiment and the main experiments (990 µg/mL) was equal to a molar concentration of about 10 mM. The test item was dissolved in deionised water.

No substantial and reproducible dose dependent increase of the mutation frequency was observed up to the maximum concentration with and without metabolic activation.

Appropriate reference mutagens (and DMBA), used as positive controls, induced a distinct increase in mutant colonies and thus, showed the sensitivity of the test system and the activity of the metabolic activation system.

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.

Based on the available data for 2-imidazolidone and its structural analogue 1-(2-hydroxyethyl) imidazolidin-2-one, 2-imidazolidone is considered to be non-mutagenic in this HPRT assay.

 

The chromosomal aberration induction properties of the substance were investigated by using Chinese hamster lung fibroblasts (CHL cells), both in the case in which S9 mix was not added (the direct method) and the case in which it was added (metabolism activation method) in a study according to EU Method B.10 and under GLP (Rohm and Haas, 1995). Based on the results of a cell multiplication inhibition test and a cell division inhibition test, the doses for the chromosomal aberration test were set at 325, 650, and 1300 µg/ml, with 10 mM as the upper limit. In the direct method, cells were treated for 24 and 48 hours. In the metabolism activation method, cells were treated for 6 hours. After the treated medium was removed and the cells were washed, culturing was performed for 18.

As a result of the test, it was concluded that no chromosomal aberrations were induced at any dose with either the direct method or the metabolism activation method.

On the other hand, clear inductions of chromosomal aberrations were observed in the positive control groups, due to the MMC and CPA treatments. Therefore, the substance does not induce chromosomal aberrations under the conditions of this test, regardless of the presence of absence of S9 mix.

Short description of key information:
The substance was not mutagenic in several Ames tests and not mutagenic in the in vivo chromosome aberration test.
No HPRT study is available for 1-(2-hydroxyethyl) imidazolidin-2-one. 2-imidazolidone is a structural analogue of 1-(2-hydroxyethyl) imidazolidin-2-one. Under the conditions of a HPRT test with 2-imidazolidone, the test substance is considered to be non-mutagenic.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available data, the substance does not need to be classified for genotoxicity according to Directive 67/548/EEC and according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.