Registration Dossier

Toxicological information

Genetic toxicity: in vitro

Currently viewing:

Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
17th November 2004 to 11th December 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was performed according to the international guidelines (OECD 471, Commission Directive No. B13/14) and in compliance with the Principles of Good Laboratory Practice Regulations.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report Date:
2005

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Beige powder

Method

Target gene:
Salmonella typhimurium
Species / strain
Species / strain / cell type:
S. typhimurium, other: TA 1535, TA 1537, TA 98, TA 100 and TA 102
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Test concentrations with justification for top dose:
Experiments without S9 mix:
The selected treatment-levels were:
• 62.5, 125, 250, 500 and 1000 μg/plate for the TA 102 strain in the first experiment and for the TA 98 strain in both experiments,
• 31.3, 62.5, 125, 250 and 500 μg/plate for the TA 1535 strain in both experiments,
• 15.6, 31.3, 62.5, 125 and 250 μg/plate for the TA 100 strain in the first experiment,
• 7.81, 15.6, 31.3, 62.5 and 125 μg/plate for the TA 1537, TA 100 and TA 102 strains in the second experiment,
• 3.91, 7.81, 15.6, 31.3 and 62.5 μg/plate for the TA 1537 strain in the first experiment.

Experiments with S9 mix:
The selected treatment-levels were:
• 62.5, 125, 250, 500 and 1000 μg/plate for the TA 100 and TA 102 strains in the first experiment and for the TA 98 strain in both experiments,
• 31.3, 62.5, 125, 250 and 500 μg/plate for the TA 1535, TA 1537 and TA 102 strains in the second experiment,
• 15.6, 31.3, 62.5, 125 and 250 μg/plate for the TA 1535 and TA 1537 strains in the first experiment,
• 7.81, 15.6, 31.3, 62.5 and 125 μg/plate for the TA 100 strain in the second experiment.
Vehicle / solvent:
DMSO
Details on test system and experimental conditions:
A preliminary toxicity test was performed to define the dose-levels of SR28043 to be used for the mutagenicity study. The test item was then tested
in two independent experiments, with and without a metabolic activation system, the S9 mix, prepared from a liver microsomal fraction
(S9 fraction) of rats induced with Aroclor 1254.
Both experiments were performed according to the direct plate incorporation method except for the second test with S9 mix, which was performed
according to the preincubation method (60 minutes, 37°C).
Five strains of bacteria Salmonella typhimurium: TA 1535, TA 1537, TA 98, TA 100 and TA 102 were used. Each strain was exposed to five
dose-levels of the test item (three plates/dose-level). After 48 to 72 hours of incubation at 37°C, the revertant colonies were
scored.
The evaluation of the toxicity was performed on the basis of the observation of the decrease inthe number of revertant colonies and/or a thinning of the bacterial lawn.
The test item SR28043 was dissolved in dimethylsulfoxide (DMSO).
The dose-levels of the positive controls were as follows:
without S9 mix:
• 1 μg/plate of sodium azide (NaN3): TA 1535 and TA 100 strains,
• 50 μg/plate of 9-Aminoacridine (9AA): TA 1537 strain,
• 0.5 μg/plate of 2-Nitrofluorene (2NF): TA 98 strain,
• 0.5 μg/plate of Mitomycin C (MMC): TA 102 strain.
with S9 mix:
• 2 μg/plate of 2-Anthramine (2AM): TA 1535, TA 1537, TA 98 and TA 100 strains,
• 10 μg/plate of 2-Anthramine (2AM): TA 102 strain.

Results and discussion

Test results
Species / strain:
S. typhimurium, other: TA 1535, TA 1537, TA 98, TA 100 and TA 102
Metabolic activation:
with and without
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
not determined
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
not specified
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
positive with metabolic activation

Under the experimental conditions, the test item showed a mutagenic activity in the bacterial reverse mutation test with Salmonella typhimurium, in
the presence of metabolic activation.
Executive summary:

Under the experimental conditions, the test item showed a mutagenic activity in the bacterial reverse mutation test with Salmonella typhimurium, in the presence of metabolic activation.