Registration Dossier

Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report date:
2002

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
yes (incl. QA statement)
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
1-(2-(4-(chloromethyl)phenoxy)ethyl)azepane hydrochloride
Cas Number:
223251-25-0
Molecular formula:
C15H23Cl2NO
IUPAC Name:
1-(2-(4-(chloromethyl)phenoxy)ethyl)azepane hydrochloride
Test material form:
solid: particulate/powder

Method

Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Species / strain / cell type:
E. coli WP2 uvr A
Metabolic activation:
with and without
Test concentrations with justification for top dose:
33, 100, 333, 1000, 2500, 5000 ug/plate
Each concentration was tested in triplicate.

Results and discussion

Test results
Species / strain:
bacteria, other: all strain tested
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Additional information on results:
The plates incubated with the test item showed normal background growth up to 5000 ug/plate with and without metabolic activation in both independent experiments.
Toxic effects, evident as a reduction in the number of revertants, were observed with and without metabolic activation in all strains used.
No substantial increase in revertant colony numbers of any of the five tester strains was observed following treatment with TSE 6 at any dose level, neither in the presence nor absence of metabolic activation (S9 mix). there was also no tendency of higher mutation rates with increasing concentrations in the range below the generally acknowledged border of biological relevance.

Any other information on results incl. tables

Toxic effects were observed at the following concentrations:

 Strain  without S9 mix (ug/plate)  with S9 mix (ug/plate)
 TA1535  2500, 5000  2500, 5000
 TA1537  2500, 5000

 -

 TA98  5000  5000
 TA100  2500, 5000  5000
 WP2 uvrA  2500, 5000  2500, 5000

Applicant's summary and conclusion

Conclusions:
It can be stated that during the mutagenicity test the test item did not induce gene mutations by base pair changes of frameshifts in the genome of the strains used.
TSE 6 is considered to be non -mutagenic in this Salmonella typhi. and Escherichia coli reverse mutation assay.