Registration Dossier

Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study

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)
Version / remarks:
only two strains were used for the experiments
Deviations:
yes
Remarks:
only two strains were used for the experiments
Principles of method if other than guideline:
only two strains were used for the experiments
GLP compliance:
yes (incl. QA statement)
Type of assay:
bacterial forward mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
1-(2-bromoethoxy)-2-methoxybenzene
EC Number:
402-010-4
EC Name:
1-(2-bromoethoxy)-2-methoxybenzene
Cas Number:
4463-59-6
Molecular formula:
C9H11BrO2
IUPAC Name:
1-(2-bromoethoxy)-2-methoxybenzene
Details on test material:
- Name of test material (as cited in study report): Carvedilol 5th intermediate (Bromoethoxy-guaiacol)
- Physical state: reddish brown crystalline powder
- Lot/batch No.: 9803
- Expiration date of the lot/batch: June 2001
- Storage condition of test material: at room temperature
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: CAR-593
- Expiration date of the lot/batch:december 2017
- Purity test date: december 2016

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: in a well-closed vial between 2-8 °C

Method

Target gene:
GC
Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 98
Species / strain / cell type:
S. typhimurium TA 100
Metabolic activation:
with and without
Metabolic activation system:
post-mitochondrial fraction S9
Test concentrations with justification for top dose:
50, 160, 500, 1000, 1600, 3200, 5000
Vehicle / solvent:
DMSO
Controls
Untreated negative controls:
yes
Positive controls:
yes
Positive control substance:
sodium azide
other: 4-Nitro-1,2-phenylenediamine, NPD
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium; in agar

DURATION
- Preincubation period: 11-14 hours
- Exposure duration: 48 hours

NUMBER OF REPLICATIONS: 2

Results and discussion

Test resultsopen allclose all
Species / strain:
S. typhimurium TA 98
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 100
Metabolic activation:
with and without
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: no mutagen potential

Applicant's summary and conclusion

Conclusions:
The reported data of this mutagenicity assay show that under the experimental conditions applied, the test item as direct acting mutagen compound and its metabolized forms induced gene mutations by base pair substitutions and in the genome of the Salmonella typhimurium TA100 tester strain. No positive effect was seen in the performed experiments in S. typhimurium TA98 (±S9 Mix).
In conclusion, the test item Bromethoxy-qvajacol (CVD 21) has mutagenic activity on Salmonella typhimurium TA100 carrying base-pair substitution in the absence and presence of exogenous metabolic activation, under the test conditions used in this study.
Unless results originated from in vivo and other in vitro mutagenicity assays, based on the results of the present bacterial reverse mutation assay the test item could be considered (categorized) as a Category 2 mutagen