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:
other: see 'Remark'
Remarks:
This study followed the procedures indicated by the following internationally accepted guidelines and recommendations: - Ninth Addendum to OECD Guidelines for Testing Chemicals, Section 4, No. 471, "Bacterial Reverse Mutation Test" - Commission Regulation (EC) No 440/2008 B13/14 - EPA Health Effects Test Guidelines, OPPTS 870.5100 "Bacterial Reverse Mutation Test" EPA 712-C-98-247 -ICH Guidance S2A: Guidance on Specific Aspects of Regulatory Genotoxicity Tests For Pharmaceuticals -ICH Guidance S2B: Genotoxicity: A Standard Battery for Genotoxicity Testing of Pharmaceuticals

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
White powder.

Method

Target gene:
Histidine, tryptophan
Species / strain
Species / strain / cell type:
other: Salmonella typhimurium TA 98, 100, 1535 and 1537 and Escherichia coli WP2 uvrA
Metabolic activation:
with and without
Metabolic activation system:
Arochlor induced / rat liver S9
Test concentrations with justification for top dose:

5000, 1581, 500, 158, 50, and 15.8 microgram/plate (initial and confirmation mutation tests)

Vehicle / solvent:
Based on the solubility test and the Range finding test the test item was dissolved in Dimethyl sulfoxide in a concentration of 100 mg/mL (stock solution).
Controls
Untreated negative controls:
yes
Remarks:
DMSO for Test Item, NPD, 9AA and 2AA Distilled water for SAZ and MMS
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: NPD, SAZ, 9AA,MMS,2AA
Details on test system and experimental conditions:
Plate incorporation technique.



Evaluation criteria:
Well established, according to Guideline.

Results and discussion

Test results
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
Preliminary experiment: effect of mutagenitity or toxicity was not observed.
Main Study: effect of mutagenitity or toxicity was not observed.
Validation study: S9 concentration increase in S9 mix has not resulted as mutagenic effect.
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):
negative

In the above experimental conditions the substance has no mutagenic activity on the applied bacterium tester strains.