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Key value for chemical safety assessment

Additional information

Reverse mutation assay 'Ames Test' using S. typhimurium and E. coli

The test substance was assessed for genetic toxicity according to EU Method B13/14 with and without metabolic activation. There was evidence of precipitation of the test substance at 333 µg/plate and cytotoxicity at > 333 µg/plate in the main test. However, there was no evidence of gentoxicity with or without metabolic activation. The test substance was considered to be non-mutagenic under the conditions of the test.

Chromosome aberration test in human lymphocytes

The test substance was also assessed according to EU Method B10 for induction of chromosome aberrations. At a concentration of 10 µg/ml the test substance precipitated in the culture medium. Therefore, a concentration of 10 µg/ml was used as the highest concentration.  The test item was considered to be non-clastogenic to human lymphocytes in vitro as the results were negative with and without metabolic activation.

Mouse lymphoma assay

The study was conducted according to a method that was designed to assess the potential mutagenicity of the test item on the thymidine kinase, TK +/-, locus of the L5178Y mouse lymphoma cell line. The method was designed to be compatible with the OECD Guidelines for Testing of Chemicals No.476 "In Vitro Mammalian Cell Gene Mutation Tests", Method B17 of Commission Regulation (EC) No. 440/2008 of 30 May 2008, the US EPA OPPTS 870.5300 Guideline, and be acceptable to the Japanese METI/MHLW guidelines for testing of new chemical substances.

The test item did not induce any toxicologically significant dose-related increases in the mutant frequency at any dose level, either with or without metabolic activation, in either the first or the second experiment.

The test item was considered to be non-mutagenic to L5178Y cells under the conditions of the test.


Justification for selection of genetic toxicity endpoint
Three separate in vitro genetic toxicity studies have been conducted on the comparable test substances considered suitable for read-across as follows:

- Bacterial Reverse Mutation Test "Ames Test"
- Chromosome Aberration Test
- In Vitro Mammalian Cell Gene Mutation Tests (Mouse Lymphoma Assay)

All 3 studies have been conducted according to standard Guidelines and GLP.

Short description of key information:
Three in-vitro studies were conducted on comparable substances:
- Reverse mutation assay 'Ames Test' using S. typhimurium and E. coli
- Chromosome aberration test in human lymphocytes
- Mouse lymphoma assay
All 3 studies gave negative results.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on negative results in the three following in-vitro studies (read-across for comparable substances), the substance is not classified for mutagencity.

 

- Reverse mutation assay 'Ames Test' using S. typhimurium and E. coli:

The tested substance was considered to be non-mutagenic under the conditions of this test.

- Chromosome aberration test in human lymphocytes:

The test substance is considered to be non-clastogenic in this chromosome aberration test.

- Mouse lymphoma assay:

The tested substance was considered to be non-mutagenic to L5178Y cells under the conditions of the test.