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Genetic toxicity in vitro

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Reference
Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: genome mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
7-16 December 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Data have been generated according to current internationally recognised study guidelines and in accordance with GLP
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
yes (incl. QA statement)
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Species / strain / cell type:
E. coli WP2 uvr A
Metabolic activation:
with and without
Metabolic activation system:
S9
Test concentrations with justification for top dose:
Concentrations of 5000; 2500; 1000; 316; 100; 31.6 and 10 μg/plate were examined in the range Finding Test. Based on the results of the Range Finding Test, the test item concentrations in the Initial Mutation Test were 5000; 1581; 500; 158.1; 50; 15.81 and 5 μg/plate. In the Confirmatory Mutation Test, concentrations of 5000; 1581; 500; 158.1; 50; 15.81; 5 and 1.581 μg/plate were examined.
Vehicle / solvent:
The behaviour of the test item solutions with the solution of top agar and phosphate buffer was examined in a preliminary solubility test. Dimethyl sulfoxide was used as solvent to prepare the stock formulation of the test material. Test solutions were freshly prepared at the beginning of the experiments in the testing laboratory by diluting the stock formulation using the selected vehicle.
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
DMSO and distilled water
Positive controls:
yes
Positive control substance:
9-aminoacridine
sodium azide
other: 4-nitro-1,2-phenylene-diamine (NPD), Methyl-methanesulfonate (MMS), 2-aminoanthracene (2AA)
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
5000 μg/plate
Vehicle controls validity:
valid
Positive controls validity:
valid
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
5000 μg/plate
Vehicle controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Precipitate was observed on the plates in the Confirmatory Mutation Test in all examined strains at 5000 μg/plate concentration with and without metabolic activation.

Untreated, negative (solvent) and positive controls were run concurrently. The mean values of revertant colony numbers of untreated, negative (solvent) and positive control plates were within the historical control range. At least five analyzable concentrations were presented in all strains of the main tests.

The reference mutagens showed a distinct increase of induced revertant colonies. The viability of the bacterial cells was checked by a plating experiment in each test. The tests were considered to be valid.

Conclusions:
Interpretation of results (migrated information):
negative

The test item had no mutagenic activity in the applied bacterium tester strains under the test conditions used in this study.
Executive summary:

The mutagenic potential has been assessed by exposure to S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 and E. coli WP2 uvr A in DMSO with and without S9 metabolic activations in accordance with the OECD 471 test guideline in compliance with GLP. Under the conditions of the test, the test substance was shown to have no mutagenic activity to bacterium tester strains.

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

Additional information

Justification for classification or non-classification

The mutagenic potential has been assessed by exposure to S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 and E. coli WP2 uvr A in DMSO with and without S9 metabolic activations in accordance with the OECD 471 test guideline in compliance with GLP. Under the conditions of the test, the test substance was shown to have no mutagenic activity to bacterium tester strains.

Additional suppoprting data available from the chromosome aberration test gives rise to some concern due to possible effects of metabolytes. No effects were observed in the absence of metabolic activation but chromosome aberrations were noted in the presence of metabolic activation. These effects will be examined in greater detail at the next supply volume when additional data will be available.

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