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Key value for chemical safety assessment

Additional information

Gene Mutation Assays

Two Bacterial Reverse mutation Assays (Ames test) were performed according to a test protocol similar to the OECD 471 test guideline with the substance. The first study (1983) was tested at higher concentrations. The second study (1984) was a repeat study done in the same laboratory as the original study, but at lower test concentrations to reduce cytotoxicity. No significant increases in the frequency of revertant colonies were recorded for any of the bacterial strains in both tests, with any dose of the test material, either with or without metabolic activation. Both tests indicate that the substance does not induce gene mutations in bacteria whereas all positive control chemicals (with and without metabolic activation) induced a significant increase in the number of of colonies. The substance is therefore considered as non-mutagenic according in the Ames test.

The inability to induce gene mutations was confirmed in mammalian cells using anin vitroforward mutation assay in CHO cells (HGPRT test). The first study (1983) was tested at higher concentrations; t. the second study (1984) was a repeat study done in the same laboratory as the original study, but at lower test concentrations to reduce cytotoxicity.

None of the test substance dose levels up to the cytotoxicity limit, either with or without metabolic activation, induced a significant increase in the mutant frequency. The substance does not induce forward mutations at the HGPRT locus in CHO cells under activation and nonactivation conditions whereas both positive control chemicals (with and without metabolic activation) induced significant mutant frequency increases. The substance is therefore considered as negative for inducing forward mutations at the HGPRT locus in CHO cells under activation and non-activation conditions used in these assays. This result confirms the results of both Ames tests and extends the non-mutagenic effect of the test substance to mammalian cells.

 

Chromosomal aberration

The clastogenic potential of the substance was determined using an in vitro chromosome aberration test in human lymphocytes, which measures the potential of a substance to increase the incidence the of structural chromosome aberrations in cultured human lymphocytes.

None of the test substance dose levels, up to the cytotoxicity limit, either with or without metabolic activation, induced significant increases in the frequency of cells with aberrations in either of two experiments. The substance does not induce structural aberrations in the chromosomes of human lymphocytes under activation and non-activation conditions, whereas both positive control chemicals (with and without metabolic activation) induced significant increases in the frequency of aberrant cells.The substance is therefore considered as negative for inducing chromosomal mutations in human lymphocyte cells under activation and non-activation conditions used in this assay.



Short description of key information:
- Ames Test 1983 single experiment (OECD 471 like, GLP, K, rel. 2): non mutagenic up to 1000 µg/plate in S. typhimurium TA 1535, TA 1537, TA 98, TA 100 & TA1538
- Ames Test 1984 single experiment (OECD 471 like, GLP, K, rel. 2): non mutagenic up to 400 µg/plate in S. typhimurium TA 1535, TA 1537, TA 98, TA 100 & TA1538
- HPRT Gene Mutation Assay 1983 single experiment (OECD 476 like, GLP, K, rel. 2): non mutagenic up to cytotoxicity limit
- HPRT Gene Mutation Assay 1984 single experiment (OECD 476 like, GLP, K, rel. 2): non mutagenic up to cytotoxicity limit
- Human lymphocyte chromosome aberration test 1999 (OECD 473, GLP, K, rel. 1): non clastogenic up to cytotoxic limit

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification for human health according to the Regulation (EC) No. 1272/2008 including the ATP2.

Self classification:

Based on the available data, no additional classification is proposed according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP).