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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
other information
Study period:
14 July 2009 - 20 July 2009
Reliability:
1 (reliable without restriction)

Data source

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
other: ICH. Topic S2A Genotoxicity: Guidance on Specific Aspects of Regulatory Genotoxicity Tests for Pharmaceuticals; CPMP/ICH/141/95 Step 5 Guideline (Into Operation April 1996)
Qualifier:
according to guideline
Guideline:
other: ICH. Topic S2B Genotoxicity: A Standard Battery for Genotoxicity Testing of Pharmaceuticals; CPMP/ICH/174/95 Step 5 Guideline (Into Operation March 1998).
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
2-(3-chloropropoxy)-1-methoxy-4-nitrobenzene
EC Number:
618-883-1
Cas Number:
92878-95-0
Molecular formula:
C10H12ClNO4
IUPAC Name:
2-(3-chloropropoxy)-1-methoxy-4-nitrobenzene
Details on test material:
Molecular formula C10H12ClNO4
Molecular weight 245.66
CAS Number 92878-95-0
Description Slightly yellow powder
Batch 18238702
Purity 99.8%
Test substance storage At room temperature protected from light
Stability under storage conditions Stable

Method

Target gene:
At least five different doses (increasing with approximately half-log steps) of the test substance were tested in triplicate in each strain. In the mutation experiment WAY-188471 was tested both in the absence and presence of S9-mix in tester strains TA1535, TA1537, TA98 and TA100.
Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 100
Details on mammalian cell type (if applicable):
Histidine mutation: hisG46/R-factor* ; Mutation type:Base-pair substitutions
received on 14-06-2006, used batch: TA100.111208
Trinova Biochem GmbH, Germany (Master culture from Dr. Bruce N. Ames)
Additional strain / cell type characteristics:
not specified
Species / strain / cell type:
S. typhimurium TA 98
Details on mammalian cell type (if applicable):
Histidine mutation: hisD3052/R-factor* ; Mutation type:Frameshift
received on 14-06-2006, used batch: TA98.111208
Trinova Biochem GmbH, Germany (Master culture from Dr. Bruce N. Ames)

*: R-factor = plasmid pKM101 (increases error-prone DNA repair)
Additional strain / cell type characteristics:
not specified
Species / strain / cell type:
S. typhimurium TA 1537
Details on mammalian cell type (if applicable):
Histidine mutation: hisC3076; Mutation type:Frameshift
received on 14-06-2006, used batch: TA1537.120609
Trinova Biochem GmbH, Germany (Master culture from Dr. Bruce N. Ames)
Additional strain / cell type characteristics:
not specified
Species / strain / cell type:
S. typhimurium TA 1535
Details on mammalian cell type (if applicable):
Histidine mutation: hisG46; Mutation type: Base-pair substitutions
received on 14-06-2006, used batch: TA1535.120609
Trinova Biochem GmbH, Germany (Master culture from Dr. Bruce N. Ames)
Additional strain / cell type characteristics:
not specified
Species / strain / cell type:
E. coli WP2 uvr A
Details on mammalian cell type (if applicable):
received on 06-02-2008, used batch: EC.100209.
Trinova Biochem GmbH, Germany (Master culture from The National Collections of Industrial and Marine Bacteria, Aberdeen, UK)
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
Rat liver microsomal enzymes were routinely prepared from adult male Wistar rats, which were obtained from Charles River, Sulzfeld, Germany.
Test concentrations with justification for top dose:
concentrations of 3, 10,33, 100, 333, 1000, 3330 and 5000 μg/plate in the absence and presence of S9-mix.
Controlsopen allclose all
Untreated negative controls:
yes
Remarks:
The vehicle of the test article, being dimethyl sulfoxide.
Negative solvent / vehicle controls:
yes
True negative controls:
yes
Positive controls:
yes
Positive control substance:
methylmethanesulfonate
Remarks:
TA100

Migrated to IUCLID6: Sigma; Concentration:650μg; solvent:DMSO
Positive controls:
yes
Positive control substance:
sodium azide
Remarks:
TA1535

Migrated to IUCLID6: Sigma, Zwijndrecht, The Netherlands; Concentration:5 μg; Solvent: Saline
Positive controls:
yes
Positive control substance:
9-aminoacridine
Remarks:
TA1537

Migrated to IUCLID6: Acros Organics, Geel, Belgium; Concentration: 60 μg; Solvent: Milli-Q water
Positive controls:
yes
Positive control substance:
2-nitrofluorene
Remarks:
TA98

Migrated to IUCLID6: Merck; Concentration: 10 μg; Solvent:DMSO
Positive controls:
yes
Positive control substance:
4-nitroquinoline-N-oxide
Remarks:
WP2uvrA

Migrated to IUCLID6: Sigma; Concentration:10 μg; Solvent:DMSO

Results and discussion

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
positive

Based on the results of this study it is concluded that WAY-188471 is mutagenic in the Salmonella typhimurium reverse mutation assay and in the Escherichia coli reverse mutation assay.