Registration Dossier

Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Qualifier:
according to guideline
Guideline:
EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
GLP compliance:
yes (incl. QA statement)
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Reference substance name:
1073607-50-7
Cas Number:
1073607-50-7
IUPAC Name:
1073607-50-7
Constituent 2
Reference substance name:
700-626-0
EC Number:
700-626-0
IUPAC Name:
700-626-0
Constituent 3
Reference substance name:
INFRAZAM
IUPAC Name:
INFRAZAM
Constituent 4
Reference substance name:
ammonium 4-[(2E)-2-[(2E)-2-[2-chloro-3-[(E)-2-[1,1-dimethyl-3-(4-sulfonatobutyl)benzo[e]indol-3-ium-2-yl]vinyl]cyclohex-2-en-1-ylidene]ethylidene]-1,1-dimethyl-benzo[e]indol-3-yl]butane-1-sulfonate
IUPAC Name:
ammonium 4-[(2E)-2-[(2E)-2-[2-chloro-3-[(E)-2-[1,1-dimethyl-3-(4-sulfonatobutyl)benzo[e]indol-3-ium-2-yl]vinyl]cyclohex-2-en-1-ylidene]ethylidene]-1,1-dimethyl-benzo[e]indol-3-yl]butane-1-sulfonate
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Molecular formula: C46H54Cl N3O6S2
Molecular weight: 844.53
Description: Brown powder (determined at NOTOX)
Batch: CH03697/BD
Purity: >84.3 – <96.6% (w/w)
Test substance storage: At room temperature in the dark
Stability under storage conditions: Stable
Expiry date: 05 October 2012 (allocated by NOTOX, 1 year after receipt of the test substance)

Method

Target gene:
histidine requiring gene (Salmonella typhimurium)
tryptophan requiring gene (Escherichia coli)
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
Metabolic activation system:
S9
Vehicle / solvent:
Dimethyl sulphoxide
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
dimethyl sulphoxide
Positive controls:
yes
Positive control substance:
other: TA1535: sodium azide, TA1537: ICR-191 (Acros Organics, Belgium), TA98: 2-nitrofluorene, TA100: methylmethanesulfonate, WP2uvrA: 4-nitroquinoline N-oxide

Results and discussion

Test resultsopen allclose all
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks:
up to the top dose of 5000µg/plate (no increase revertants)
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Remarks:
up to the top dose of 5000µg/plate (precipitation observed at 333µg/plate)(no reduction bacterial background and no decrease revertants)
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks:
up to the top dose of 5000µg/plate (no increase revertants)
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Remarks:
up to the top dose of 5000µg/plate (precipitation observed at 333µg/plate)(no reduction bacterial background and no decrease revertants)
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks:
(no upper limit as no precipitation at 333µg/plate; increase observed but not biologically relevant increase of revertants)
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Remarks:
(no upper limit as no precipitation at 333µg/plate; no reduction bacterial background and no decrease revertants)
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks:
(no upper limit as no precipitation at 333µg/plate; no increase of revertants)
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Remarks:
(no upper limit as no precipitation at 333µg/plate; no reduction bacterial background and no decrease revertants)
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks:
up to precipitation at 1000µg/plate (no increase revertants)
Cytotoxicity / choice of top concentrations:
no cytotoxicity, but tested up to precipitating concentrations
Remarks:
precipitation at 1000µg/plate (no reduction bacterial background and no decrease revertants)
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 100
Metabolic activation:
without
Genotoxicity:
negative
Remarks:
up to precipitation at 1000µg/plate (increase observed but not biologically relevant increase of revertants)
Cytotoxicity / choice of top concentrations:
no cytotoxicity, but tested up to precipitating concentrations
Remarks:
precipitation at 1000µg/plate (no reduction bacterial background and no decrease revertants)
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with
Genotoxicity:
negative
Remarks:
up to precipitation at 1000µg/plate (no increase revertants)
Cytotoxicity / choice of top concentrations:
no cytotoxicity, but tested up to precipitating concentrations
Remarks:
precipitation at 1000µg/plate (no reduction bacterial background and no decrease revertants)
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks:
up to precipitation at 1000µg/plate (no increase revertants)
Cytotoxicity / choice of top concentrations:
no cytotoxicity, but tested up to precipitating concentrations
Remarks:
precipitation at 1000µg/plate (no reduction bacterial background and no decrease revertants)
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
The first and second above mentioned results are the dose range finding test, for which for the metabolic activation 5% S9 is used.
The third and fourth above mentioned results are the first mutation assay, for which for the metabolic activation 5% S9 is used.
The fifth above mentioned result is the second mutation assay, for which for the metabolic activation 5% S9 is used.
The sixth until last above mentioned results are the third mutation assay, for which for the metabolic activation 10% S9 is used.
Remarks on result:
other: strain/cell type: TA1537 and TA98
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

Based on the results of this study it is concluded that the test substance is not mutagenic in the Salmonella typhimurium reverse mutation assay and in the Escherichia coli reverse mutation assay.