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Key value for chemical safety assessment

Additional information

Procedure and observations

An Ames test and a micronucleus test in vivo were performed according OECD guideline 471 ad 474 to evaluate genetic toxicity of the test substance.

The ames test was performed to investigate the potential of the test article to induce gene mutations using the Salmonella typhimurium strains TA 1535, TA 1537, TA 1538, TA 98 and TA 100 and in addition the Escherichia coli strains WP2 and WP2 uvrA. The assay was performed with and without liver microsomal activation. Each concentration, including the controls, was tested in triplicate. The test article was tested at the following concentrations: 5, 10, 50, 100, 500, 1000 and 5000 ug/0.1 ml.

The plates incubated with the test article showed normal background growth up to 5000 µg/0.1 ml with and without metabolic activation in all independent experiments. A growth inhibiting effect was observed at the highest concentration with the strains TA 1535, TA 1537 and TA 1538. No substantial increases in revertant colony numbers of any of the tester strains were observed following treatment with the test substance at any dose level, neither in the presence nor in the absence of metabolic activation.

Additionally, a micronucleus test in chinese hamster was performed. Based upon the results of a tolerability test, a single dose of 4000 mg/kg bw was administered by oral gavage to male and female animals (8/sex). Animals were sacrificed and samples of bone marrow were taken after 16, 24 and 48h, respectively. Bone marrow smears were made, air dried and dyed with Giemsa solution. 1000 polychromatic erythrocytes per hamster were scored for incidence of micronuclei. A positive control experiment was performed with cyclophosphamide.

The bone marrow smears from the animals treated with the dose of 4000 mg/kg of the test substance showed no increase in the number of micronucleated polychromatic erythrocytes in comparison with the negative control animals at all three sampling times.

 

 

Discussion

Treatment of different bacteria strains with the test substance in presence and absence of S9-mix did not induce increases in revertant colonies. Single oral application of the test article to Chinese hamsters did not cause an increase of polychromatic micronucleated erythrocytes. Thus, the test item is considered as not mutagenic and not clastogenic under the conditions of these tests.


Short description of key information:
An Ames test and a micronucleus test in Chinese hamster was performed according OECD guideline 471 and 474 to evaluate the mutagenic potential of the test substance. The test item did neither induce mutations in vitro nor formation of micronuclei in vivo. Therefore, the substance is considered as non-mutagenic under the conditions of these tests.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitablefor classification purposes under 67/548/EEC. As a result the substance is notconsidered to be classified for genotoxicityunder Directive 67/548/EEC, as amended for the 28th time in Directive 2001/59/EC.

 

 

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for genotoxicityunder Regulation (EC) No. 1272/2008.