Registration Dossier

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report Date:
1995

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
only 4 strains were used.
Qualifier:
according to
Guideline:
EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
Principles of method if other than guideline:
The tester strains of Salmonella typhimurium can only survive and grow on medium that contains excess histidine. However, in the presence of a mutagenic chemical, the defective histidine gene may be mutated back to the functional state, allowing the bacterium to grow on standard medium that does not contain supplemental histidine. These mutations, which lead to a regaining of normal activity or function, are called "back" or "reverse" mutations and they are counted. The performance of the test with and without an external metabolising system ensures the detection of the mutagenic action of the test substance itself as well as of its metabolites.
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: pellets

Method

Species / strainopen allclose all
Species / strain:
S. typhimurium TA 97
Metabolic activation:
with and without
Metabolic activation system:
Induced male Sprague Dawley rat liver S9
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Metabolic activation system:
Induced male Sprague Dawley rat liver S9
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Metabolic activation system:
Induced male Sprague Dawley rat liver S9
Species / strain:
S. typhimurium TA 102
Metabolic activation:
with and without
Metabolic activation system:
Induced male Sprague Dawley rat liver S9
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with and without
Metabolic activation system:
Induced male Sprague Dawley rat liver S9
Test concentrations with justification for top dose:
6 to 1500 µg/plate.
Vehicle:
Dimethyl sulfoxide.
Controls
Negative controls:
yes
Solvent controls:
yes
Remarks:
dimethylsulfoxide
Positive controls:
yes
Positive control substance:
other: For strains tested in the absence of S9: TA98, 2-nitrofluorene or alternatively, 4-nitro-o-phenylenediamine, TA100 and TA1535, sodium azide, TA97, 9-aminoacridine. For strains tested with S9: All strains, 2-aminoanthracene or sterigmatocystin.

Results and discussion

Test results
Species / strain:
other: each used strain
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity:
not specified
Vehicle controls valid:
yes
Positive controls valid:
yes
Remarks on result:
other: all strains/cell types tested

Applicant's summary and conclusion

Conclusions:
Interpretation of results:
negative
Executive summary:

An Ames test with 4 strains of S. typhimurium was performed: 1 -CFT was negative in each strain and also with and without an external metabolic activation system, up to toxic concentrations.