Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
other information
Study period:
Jun-Aug 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: well reported GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report date:
1997

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
no bacteria strain included to detect cross-linking mutagens
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
7α-bromo-5,6β-epoxy-15β,16β-methylene-3β-pivaloyloxy-5β-androstan-17-one
EC Number:
617-834-1
Cas Number:
863329-69-5
Molecular formula:
C25H35BrO4
IUPAC Name:
7α-bromo-5,6β-epoxy-15β,16β-methylene-3β-pivaloyloxy-5β-androstan-17-one
Details on test material:
- Name of test material (as cited in study report): ZK 137314
- Batch No.: 21608209

Method

Target gene:
Histidine gene locus
Species / strain
Species / strain / cell type:
other: S. typhimurium TA 1535, TA 100, TA 1537, TA 1538, TA 98
Metabolic activation:
with and without
Metabolic activation system:
liver S9-mix from Aroclor 1254 -treated rats
Test concentrations with justification for top dose:
Bromepoxid: six concentrations from 0.05 to 2.5 mg/plate
Sodium azide: 5 µg/plate (TA 1535 and TA 100)
2-Nitrofluorene: 10 µg/plate (TA 1538 and TA 98)
9-Acridinamine: 100 µg/plate (TA 1537)
Benzo[a]pyrene: 2.5 µg/plate (TA 100 and TA 98)
Cyclophosphamide: 400 µg/plate (TA 1535)
2-Aminoanthracene: 2 µg/plate
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
other: Sodium azide (TA 1535 and TA 100), 2-Nitrofluorene (TA 1538 and TA 98), 9-Acridinamine (TA 1537), Benzo[a]pyrene (TA 100 and TA 98), Cyclophosphamide (TA 1535), 2-Aminoanthracene

Results and discussion

Test results
Species / strain:
other: Salmonella typhimurium strains TA 1535, TA 100, TA 1537, TA 1538, TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
growth inhibition was observed at the highest dose tested in the strains TA 1537, TA 1538 and TA 98; precipitates in the agar were found in all strains tested starting at 0.5 mg/plate
Vehicle controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Executive summary:

Bromepoxid was tested in the Salmonella/microsome test for point-mutagenic effects in doses up to 2500 µg/plate on the five histidine-auxotrophic Salmonella typhimurium LT2 strains TA 1535, TA 100, TA 1537, TA 1538 and TA 98.

A cytotoxic effect was seen at the highest dose tested (2.5 mg/plate) in the strains TA 1537, TA 1538 and TA 98. Precipitates in the agar were found starting at 0.5 mg/plate in all strains tested.

There was no evidence for a mutagenic activity of Bromepoxid, when tested up to the cytotoxic and precipitating dose levels in the absence and presence of S9 mix.