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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information
According to the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) Part 3 Chapter 3.5 this substance is not causing concern to be mutgenetic/genetic toxic.
Link to relevant study records
Reference
Endpoint:
in vitro gene mutation study in mammalian cells
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: according to EC Directive 92/69/EEC and Regulation EC/440/2008 guideline methods under GLP conditions
Qualifier:
according to
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
GLP compliance:
yes
Type of assay:
mammalian cell gene mutation assay
Species / strain / cell type:
mouse lymphoma L5178Y cells
Details on mammalian cell type (if applicable):
- Type and identity of media:
- Periodically "cleansed" against high spontaneous background: yes
Metabolic activation:
with and without
Metabolic activation system:
S9
Test concentrations with justification for top dose:
8.83 to 2260 µg/ml
Vehicle / solvent:
DMSO
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
ethylmethanesulphonate
Remarks:
Migrated to IUCLID6: ethylmethanesulphonate in in the absence of of metabolic activation; cyclophosphamide in the presence of metabolic activation
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined
Vehicle controls validity:
valid
Positive controls validity:
valid
Additional information on results:
Two independent experiments wre performed. In Experiment 1, L5178Y TK +/- 3.7.2c mouse lymphoma cells (heterozyous at the thymidine kinase locus) were treated with the test material at up to eight dose levels, in duplicate, together with vehicle (solvent) and positive controls using 4 -hour exposure groups both in the asence and presence of metabolic activation (2% S9). In experiment 2, the cells were treated with the test material at up to eight dose levels using a 4 -hour exposure group in the absence of metabolic activation.
The dose range of test material was selected following the results of a preliminary toxicity test and for the first experiment was 4.38 to 140 µg/ml in the absence of metabolic activation, and 17.5 to 280 µg/ml in the presence of metabolic activation. For the second experiment the dose range was 4.38 to 140 µg/ml in the absence of metabolic activation, and 17.5 to 210 µg/ml in the presence of metabolic activation.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.
Conclusions:
Interpretation of results (migrated information):
negative non-mutagenic

The test material was considered to be non-mutagenic to L5178Y cells under the conditions of the test.

Executive summary:

Introduction:

The study was conducted according to a method that was designed to assess the potential mutagenicity of the test material on the thymidine kinase, TK +/-, locus of the L5178Y mouse lymphoma cell line, >>The method used meets the requirements of the OECD (476) and the Method B17 of Commission Regulation (EC) No. 440/2008 of 30 May 2008.

Methods:

Two independent experiments wre performed. In Experiment 1, L5178Y TK +/- 3.7.2c mouse lymphoma cells (heterozyous at the thymidine kinase locus) were treated with the test material at up to eight dose levels, in duplicate, together with vehicle (solvent) and positive controls using 4 -hour exposure groups both in the asence and presence of metabolic activation (2% S9). In experiment 2, the cells were treated with the test material at up to eight dose levels using a 4 -hour exposure group in the absence of metabolic activation.

The dose range of test material was selected following the results of a preliminary toxicity test and for the first experiment was 4.38 to 140 µg/ml in the absence of metabolic activation, and 17.5 to 280 µg/ml in the presence of metabolic activation. For the second experiment the dose range was 4.38 to 140 µg/ml in the absence of metabolic activation, and 17.5 to 210 µg/ml in the presence of metabolic activation.

Results:

THe maximum dose level used in the mutagenicity test was limited by test material-induced toxicity. Precipitate of the test material was not observed at any of the dose levels in the mutagenicity test. The vehicle (solvent) controls had acceptable mutant frequency values that were within the normal range for the L5178Y cel line at the TK +/- locus. The positive control materials induced marked increases in the mutant frequency indicating the satisfactory perfomance of the test and of the activity of the metabolising system.

The test material did not induce any toxicologically significant dose-related increases in the mutant frequency at any dose level, either with or without metabolic activation, in either the first or the second experiment.

Conclusion:

The test material was considered to be non-mutagenic to L5178Y cells under the conditions of the test.

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

Additional information

Additional information from genetic toxicity in vitro:

The test material was considered to be non-mutagenic according to the test conditions as given in OCED guidelines 471, 473 and 476.


Justification for selection of genetic toxicity endpoint
This study contains data which meets the criteria set forth in Regulation EC No. 440/2008 for filling REACH endpoints. The data is generated in a reliable laboratory using established protocols. It is supported by studies following OECD TG 471 and 473.

Justification for classification or non-classification

According to the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) Part 3 Chapter 3.5 this substance is not causing concern to be mutgenetic/genetic toxic.