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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Study period:
30/08/2006 - 18/09/2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Version / remarks:
OECD Guidelines for Testing of Chemicals: Guideline no. 471: "Genetic Toxicology: Bacterial Reverse Mutation Test" (Adopted July 21, 1997)
Qualifier:
according to
Guideline:
EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
Version / remarks:
European Economic Community (EEC). Directive 2000/32/EC, Part B: Methods for the Determination of Toxicity; B.13/14: "Mutagenecity: "Reverse Mutation Test using bacteria". EEC Publication Commission Directive (Published June 8, 2000)
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Test material form:
solid: particulate/powder
Details on test material:
- Description: dark purple powder
- Solubility in the water: <= 0.412 g/L
- Melting point: > 250 °C
- Boiling point: > 250 °C
- Explosion: not explosion
- Log Pow: >= 3.3
- Test substance storage: at room temperature in the dark, 20°C, dry store
- Stability under storage conditions: stable
Specific details on test material used for the study:
Stability at higher temperature: Maximum temperature 75°C, maximum duration 48 hours
Stability in vehicle: Dimethyl sulfoxide: At least 96 hours
Solubility in vehicle: Dimethyl sulfoxide: Yes

Method

Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Details on mammalian cell type (if applicable):
TA1537 and TA98 are capable of detecting frameshift mutagens
TA1535 and TA100 are capable of detecting base-pair substitution mutagens (ref. 1, 2, 3, 4 and 5)
Species / strain / cell type:
E. coli WP2 uvr A
Details on mammalian cell type (if applicable):
capable of detecting base-pair substitution mutagens (ref. 1, 2, 3, 4 and 5)
Vehicle / solvent:
dimethyl sulfoxide
Controls
Untreated negative controls:
yes
Remarks:
The vehicle of the substance, being dimethyl sulfoxide
Positive controls:
yes
Positive control substance:
4-nitroquinoline-N-oxide
9-aminoacridine
2-nitrofluorene
sodium azide
methylmethanesulfonate
Details on test system and experimental conditions:
Test system: Salmonella typhimurium bacteria and Escherichia coli bacteria
Test substance preparation: The test substance was dissolved in dimethyl sulfoxide of spectroscopic quality (Uvasol, Merck, Darmstadt, Germany). Test substance concentrations were used within 4 hours after preparation.
Rationale for test conditions:
Recommended test system in international guidelines (e.g. OECD and EEC)

Results and discussion

Test resultsopen allclose all
Key result
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 1537
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid

Applicant's summary and conclusion

Conclusions:
not mutagenic under the conditions of this test
Executive summary:

All bacterial strains showed negative responses over the entire dose range, i.e. no significant dose-related increase in the number of relevants in independently repeated experiments.

The negative and strain-specific positve control values wer within our laboratory historical control data ranges indicating that the test conditions were adequate and that the metabolic activation system functioned properly.

Based on the results of this study it is concluded that SXjul2006 is not mutagenic in the Salmonella typhimurium reverse mutation assay and in the Escherichia coli reverse mutation assay.