Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Atmer 163 showed neither mutagenic nor clastogenic activity in the in vitro assays of bacterial and mammalian cell cultures.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

An Ames test was performed according to OECD guideline 471 with the S. typhimurium strains TA 1535, TA 1537, TA 98 and TA 100 and the E. coli strain WP2 uvrA (pKM101). The strains were treated with 2, 5, 10, 20, 50, 100 µg/plate with and without metabolic activation with rat liver S9-Mix. Positive and solvent controls were valid and Atmer 163 showed no mutagenic activity in any of the tested strains at any concentration with and without metabolic activation.  

A mammalian cell gene mutation assay was performed with mouse lymphoma L5178Y cells according to OECD guideline 476 (CTL/VV0318). The cells were treated with 1, 2, 4, 6, 8, 10 µg/mL without and 1, 2, 4, 10, 15, 20 µg/mL with S9-mix in the first experiment and with 4, 6, 8, 10, 15, 20 µg/mL without and 4, 6, 8, 10, 15, 20 µg/mL with S9-mix in the second experiment. In each case Atmer 163 was found to be biologically active in the test system, causing concentration related reductions in survival down to a value of 11% in both the presence and absence of S9-mix. No reproducible increases in mutant frequency, above the solvent control values, were recorded for cultures treated with Atmer 163 in either the presence or absence of S9-mix. The data obtained in this study therefore show that the test sample of Atmer 163 is not mutagenic in L5178Y TK+/- cells following in vitro treatment in either the presence or absence of S9-mix.

A chromosome aberration assay was performed according to OECD guideline 473 in primary human peripheral blood cultures (CTL/SV1280). The cells were treated in two independent experiments: In experiment 1 with S9-mix for 3h with 5, 10, 20 µg/mL, without S9-mix for 3h with 7.5, 10, 13 µg/mL and in experiment 2 with S9-mix for 3h with 5, 7.5, 10 µg/mL  and without S9-mix for 20h with 0.5, 2.5, 5 µg/mL. A small, but statistically significant increase in the percentage of aberrant cells, compared to the solvent control, was observed in Experiment 2 in the absence of S9 -mix. As this value is only just outside of the historical control range it is considered to be of no biological significance. No other statistically significant increases in the percentage of aberrant cells, compared to the solvent control values, were recorded. The sensitivity of the test system, and the metabolic activity of the S9-mix employed, were clearly demonstrated by the increases in the frequencies of aberrant cells induced by the positive control agents, mitomycin C and cyclophosphamide. The data obtained in this study therefore show that the test sample of Atmer 163 did not induce chromosomal damage in human peripheral blood lymphocytes following in vitro treatment in either the presence or absence of S9-mix.






Justification for classification or non-classification

Ames test, gene mutation test in mouse lymphoma cells and chromosome aberration test in human primary lymphocytes showed negative results after application of Atmer 163, but had valid positive controls.

Based on the available data, Atmer 163 does not meet the classification criteria to classify for genetic toxicity according to Regulation (EC) 1272/2008 and therefore the data is conclusive, but not sufficient for classification.