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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:
July/August 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
The study was performed in compliance with the following regulations or guidelines:
• OECD Guidelines for Testing of Chemicals No. 471 (1997) "Bacterial Reverse Mutation Test"
• Method B13/14 of Commission Regulation (EC) number 440/2008 of 30 May 2008.
• USA, EPA OCSPP harmonized guideline 870.5100 - Bacterial Reverse Mutation Test
• Japanese Ministry of Economy, Trade and Industry, Japanese Ministry of Health, Labour and Welfare and Japanese Ministry of Agriculture, Forestry and Fisheries

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report date:
2017

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:
617-898-0
EC Number:
617-898-0
Cas Number:
866462-52-4
Molecular formula:
C17 H21 N O5
IUPAC Name:
617-898-0
Test material form:
solid: particulate/powder
Details on test material:
Off white powder
Specific details on test material used for the study:
Batch 18126644

Method

Target gene:
Salmonella typhimurium : TA1537 - TA98 - TA1535 - TA100
Escherichia coli : WP2uvrA-
Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1537
Details on mammalian cell type (if applicable):
obtained from:
• University of California, Berkeley, on culture discs, on 04 August 1995
• British Industrial Biological Research Association, on a nutrient agar plate, on 17 August 1987
Additional strain / cell type characteristics:
other: Genotype : his C 3076; rfa-; uvrB-: frame shift mutations
Species / strain / cell type:
S. typhimurium TA 98
Details on mammalian cell type (if applicable):
The bacteria used in the test were obtained from:
• University of California, Berkeley, on culture discs, on 04 August 1995
• British Industrial Biological Research Association, on a nutrient agar plate, on 17 August 1987
Additional strain / cell type characteristics:
other: Genotype : his D 3052; rfa-; uvrB-;R-factor
Species / strain / cell type:
S. typhimurium TA 1535
Details on mammalian cell type (if applicable):
The bacteria used in the test were obtained from:
• University of California, Berkeley, on culture discs, on 04 August 1995
• British Industrial Biological Research Association, on a nutrient agar plate, on 17 August 1987
Additional strain / cell type characteristics:
other: Genotype : his G 46; rfa-; uvrB-: base-pair substitutions
Species / strain / cell type:
S. typhimurium TA 100
Details on mammalian cell type (if applicable):
The bacteria used in the test were obtained from:
• University of California, Berkeley, on culture discs, on 04 August 1995
• British Industrial Biological Research Association, on a nutrient agar plate, on 17 August 1987
Additional strain / cell type characteristics:
other: Genotype : his G 46; rfa-; uvrB-;R-factor
Species / strain / cell type:
E. coli WP2 uvr A
Details on mammalian cell type (if applicable):
The bacteria used in the test were obtained from:
• University of California, Berkeley, on culture discs, on 04 August 1995
• British Industrial Biological Research Association, on a nutrient agar plate, on 17 August 1987
Additional strain / cell type characteristics:
other: Genotype : his G 46; rfa-; uvrB-;R-factor
Metabolic activation:
with and without
Metabolic activation system:
S9
Test concentrations with justification for top dose:
The maximum concentration was 5000 μg/plate (the maximum recommended dose level).Eight concentrations of the test item (1.5, 5, 15, 50, 150, 500, 1500 and 5000 μg/plate) were assayed in triplicate against each tester strain, using the direct plate incorporation method.
Vehicle / solvent:
Dimethylsulfoxyde
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Remarks:
triplicate

Results and discussion

Test resultsopen allclose all
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:
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:
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
Key result
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
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

Applicant's summary and conclusion

Conclusions:
Azepan was considered to be non-mutagenic under the conditions of this test.
Executive summary:

Azepan was considered to be non-mutagenic under the conditions of this test.