Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

An increase in the number of his+ or trp+ revertants was not observed in the standard plate test either with or without S-9 mix. Therefore, the test substance is not mutagenic in the Ames test under the experimental conditions chosen.
Under the experimental conditions reported the test item did not induce gene mutations at the HPRT locus in V79 cells. Therefore, the test substance is considered to be non-mutagenic in this HPRT assay.
It can be stated that under the experimental conditions reported, the test substance did not induce micronuclei in V79 cells (Chinese hamster cell line) in vitro in the absence and presence of metabolic activation. Therefore, the test substance is considered to be non-mutagenic in this in vitro test system, when tested up to the highest required or evaluable concentrations.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Mode of Action Analysis / Human Relevance Framework

No information available.

Additional information

1,2-Dimethylimidazole was tested in the Ames reverse mutation assay (GLP compliant study according to OECD guideline 471 and 472) using Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 and Escherichia coli WP2 uvr A at 20 to 5000 µg/plate (standard plate and preincubation test) with and without metabolic activation (1998; RL1). Under the conditions tested,1,2-dimethylimidazole was not mutagenic in any of the S. typhimurium strains and E.coli WP2 uvr A.

In a GLP-compliant study performed according to OECD guideline 476 the test item was assessed for its potential to induce gene mutations at the HPRT locus using V79 cells of the Chinese hamster (2013; RL1). The study was performed in two independent experiments, using identical experimental procedures. In the first experiment the treatment period was 4 hours with and without metabolic activation (assayed concentrations 62.5, 125.0, 250.0, 500.0 and 1000.0 µg/mL). The second experiment was performed with a treatment time of 4 hours with and 24 hours without metabolic activation (assayed concentrations: 62.5, 250.0, 500.0 and 1000.0 µg/mL (4h with S9), and 31.3, 62.5, 125.0, 250.0 µg/mL (24h without S9)). The test item was dissolved in deionised water. In the experimental part of the second experiment without metabolic activation (24 hour treatment) the concentration range was limited by cytotoxic effects. Relevant cytotoxic effects indicated by a relative cloning efficiency I or cell density below 50% in both parallel cultures occurred in the second experiment at 125 and 250 μg/mL without metabolic activation. The recommended cytotoxic range of approximately 10-20% relative cloning efficiency I or relative cell density was covered. In all of the experimental parts using 4 hours treatment with and without metabolic activation the concentration range went up to 1000 μg/mL or approximately 10 mM. 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 (EMS 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. Therefore, the test substance is considered to be non-mutagenic in this HPRT assay.

In a GLP-compliant study, performed according to OECD guideline 487, the test substance (dissolved in deionised water) was assessed for its potential to induce micronuclei in V79 cells of the Chinese hamster in vitro in the absence and presence of metabolic activation by S9 mix (2013; RL1). Four independent experiments were performed. In Experiment IA the exposure period was 4 hours with and with out metabolic activation. In Experiment IB the exposure period was 4 hours with metabolic activation. In Experiment IIA and IIB the exposure periods were 24 hours without S9 mix and 4 hours with metabolic activation. The cells were prepared 24 hours after start of treatment with the test item. In each experimental group two parallel cultures were set up and at least 1000 cells per culture were scored for micronuclei. The highest applied concentration (1000.0 µg/mL; approx. 10 mM) was chosen with regard to the molecular weight and the preliminary purity (96.0 %) of the test item and with respect to the OECD Guideline No. 487. No visible precipitation of the test item in the culture medium was observed. No relevant influence on osmolarity was observed. Phase separation was observed microscopically in the presence of S9 mix in Experiment IIA at 600.0 µg/mL and above and in Experiment IIB at 900.0 µg/mL and above at the end of treatment. The pH was adjusted to physiological values. In Experiment IA in the absence of S9 mix and in Experiment IB and IIB in the presence of S9 mix no cytotoxicity was observed up to the highest applied concentration. In Experiment IA in the presence of S9 mix, in Experiment IIA in the absence and presence of S9 mix and in Experiment IIB in the absence of S9 mix concentrations showing clear cytotoxic effects were not evaluable for cytogenetic damage. In Experiment IA in the presence of S9 mix increases in micronucleated cells above the range of the laboratory historical control data (0.05 - 1.70 % micronucleated cells) were observed after treatment with 62.5 and 125.0 µg/mL (2.13 and 1.80 % micronucleated cells).The values were not statistically significant. In Experiment IB these findings could not be confirmed. All values were within the range of the laboratory historical control data (0.05 -1.70 % micronucleated cells) and were not statistically significant. In Experiment IIA in the absence of S9 mix one statistically significant increase, clearly exceeding the laboratory historical solvent control data range (without S9 mix: 0.15 – 1.50 % micronucleated cells) was observed after treatment with 250.0 µg/mL (3.18 %). In the presence of S9 mix increases above the laboratory historical solvent control data range (with S9 mix: 0.05 – 1.70 % micronucleated cells) were observed after treatment with 600.0, 700.0 and 800.0 µg/mL (1.90, 1.83 and 2.13 %, respectively). The highest value was statistically significant. In the confirmatory Experiment IIB in the absence of S9 mix statistically significant increases (1.15, 1.15, 1.00 % micronucleated cells) within the laboratory historical solvent control data range (0.15 – 1.50 % micronucleated cells) were observed after treatment with 325.0, 350.0 and 400.0 µg/mL. In the presence of S9 mix one statistically significant increase (1.15 % micronucleated cells) within the laboratory historical solvent control data range (0.05 –1.70 % micronucleated cells) was observed after treatment with 1000.0 µg/mL and thus the findings could not be confirmed. Appropriate mutagens were used as positive controls. They induced statistically significant increases in the percentage of micronucleated cells. In conclusion, it can be stated that under the experimental conditions reported, the test substance did not induce micronuclei in V79 cells (Chinese hamster cell line) in vitro in the absence and presence of metabolic activation. Therefore, the test substance is considered to be non-mutagenic in this in vitro test system, when tested up to the highest required or evaluable concentrations.

Justification for classification or non-classification

Based on the results of the available data, 1,2-dimethylimidazole does not need to be classified 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.