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Key value for chemical safety assessment

Additional information

The gene mutation potential of UMA121 was examined in a bacterial reverse mutation assay (Ames test) according to OECD 473 and GLP (Donath, 2012). Test substance concentrations of 31.6 – 5000 µg/plate were investigated in S. typhimurium tester strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in two independent experiments (plate incorporation and preincubation method). The test substance did not induce reversions in any of the strains tested with or without metabolic activation.The used positive controls were valid.No cytotoxicity was observed in any strain and at any concentration tested. Precipitation of the test substance was observed in all tester strains at 1000 µg/plate and higher without metabolic activation and at 2500 µg/plate and higher with metabolic activation.

Under the conditions of this test, UMA121 was not considered to be genotoxic.

 

Gene mutation at the thymidine kinase locus was investigated in mouse lymphoma L5178Y cells according to OECD 476 and GLP (Zeller, 2013). L5178Y cells were incubated with test substance concentrations of 35 to 5000 µg/mL with and without metabolic activation in two independent experiments. The test substance did not induce gene mutation. The used positive controls were valid. Cytotoxic effects were observed only in Experiment II at 2000 and 2500 µg/mL without metabolic activation and at 5000 µg/mL with metabolic activation on the basis of relative total growth. However, the test substance precipitated at 450 µg/mL and higher.

Under the conditions of this test, UMA121 was not considered to be genotoxic.

 

In an in vitro cytogenetic assay according to OECD 473 and GLP, the clastogenic properties of UMA121 were investigated in Chinese hamster V79 cells (Hofman-Hüther, 2013). The chromosome aberration test was conducted in two independent experiments in the presence and absence of metabolic activation with test substance concentrations of 31.3 to 5000 µg/mL culture medium.

No increase in chromosomal aberrations was observed in the first experiment after 4 h incubation with the test substance with and without metabolic activation.

Because of the negative results of the short-term treatment, a second experiment without metabolic activation was performed with continuous treatment for 20 h. An additional set of cells was treated for 4 h with the test substance in presence of metabolic activation. Again, there was no increase in chromosomal aberration at any time point.

The positive controls were valid. Precipitation of the test substance was noted in both experiments with and without metabolic activation at concentrations of 300 µg/mL and higher as well as 1000 µg/mL and higher, respectively. Cytotoxic effects were observed in Experiment I only at 1000 µg/mL without metabolic activation (regarding a mitotic index of 57 %). In Experiment II, cytotoxicity was observed at 1000 and 5000 µg/mL without metabolic activation (regarding mitotic indices of 65 and 69 %, respectively) and at 300 µg/mL with metabolic activation (regarding a relative cell density of 55 %).

Under the conditions of this test, UMA121 was not considered to be clastogenic.


Justification for selection of genetic toxicity endpoint
No study was selected, since all available in vitro genetic toxicity studies were negative.

Short description of key information:
Gene mutation (Ames test, OECD 471): negative
Gene mutation (Mouse Lymphoma Assay, OECD 476): negative
Chromosome aberration (in vitro chromosome aberration test, OECD 473): negative

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The available data on genetic toxicity of the test substance does not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and is therefore conclusive but not sufficient for classification.