Carbamic acid, N-[[5-[[[2-[2-(dimethylamino)ethoxy]ethoxy]carbonyl]amino]-1,3,3-trimethylcyclohexyl]methyl]-, 2-[2-(dimethylamino)ethoxy]ethyl ester

Endpoint summary

Additional information

UAX-1179 was tested in three different GLP-Guideline studies for genetic toxicity in vitro.

UAX-1179 induced neither in an incorporation test nor in a pre-incubation test using Salmonella typhimurium strains TA 1535, TA 1537, TA 98, and TA 100 and the Escherichia coli strain WP2 uvrA gene mutations. The substance was tested up to 5000 µg/plate with and without metabolic activation. No toxic effects occurred in the test groups, except for strain TA 1537, where a minor toxic effect was observed at 5000 µg/plate without S9 mix. Under the experimental conditions the test item did not induce mutations by base pair changes or frameshifts in the genome of the strains used (Poth, 2002).

The test item UAX-1179 was assessed for its potential to induce structural chromosome aberrations in V79 cells of the Chinese hamster in vitro in two independent experiments by M.Schulz, 2002. No clear dose-related toxic effects were observed after treatment with up to 5000 µg/mL (~ 10mM) of the test item. No statistically significant or biologically relevant increase in the number of cells carrying structural chromosomal aberrations was observed after treatment with the test item. No increase in the frequencies of polyploid metaphases was found after treatment with UAX-1179 compared to the frequencies of the controls. UAX-1179 is considered to be non-clastogenic in this chromosome aberration test either with or without S9 mix.

The test item UAX-1179 was assessed in a GLP study according to OECD 476 for its potential to induce mutations at the mouse lymphoma thymidine kinase locus using the cell line L5178Y.

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 h. The second experiment was performed with a treatment period of 24 hours in the absence of metabolic activation and 4 hours in the presence of metabolic activation. The selection of the maximum concentration of 4960 µg/mL was based on data from the pre-experiment.

Relevant toxic effects indicated by a relative total growth of less than 50 % of relative total growth were observed in both parallel cultures in experiment I at 2480 µg/mL in the absence of metabolic activation, and at 4960 µg/mL in the presence of metabolic activation. In the second experiment toxic effects as described above occurred at 2480 µg/mL without metabolic activation (24 hours treatment), and at 3720 µg/mL with metabolic activation.

In Experiment I and II no biologically relevant increase of mutants was found after treatment with the test item (with and without metabolic activation). No dose-response relationship was observed. Appropriate reference mutagens were used as positive controls and showed a distinct increase in induced mutant colonies, indicating that the tests were sensitive and valid.

UAX-1179 did not induce mutations in the mouse lymphoma thymidine kinase locus assay using the cell line L5178Y in the absence and presence of metabolic activation.

Short description of key information:
genetic toxicity in-vitro: negative

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

DSD and CLP: Based on in vitro results in bacterial test systems and in mammalian cells UAX-1179 does not need to be classified.