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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July 12 to August 2, 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD guidelines and according to GLP principles

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
The temperature was above the protocolled range of 37.0 °C for approximately 60 minutes in the second mutation experiment (with a maximum of 38.6 °C). The study integrity was not adversely affected by the deviation.
Qualifier:
according to
Guideline:
EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
Deviations:
yes
Remarks:
The temperature was above the protocolled range of 37.0 °C for approximately 60 minutes in the second mutation experiment (with a maximum of 38.6 °C). The study integrity was not adversely affected by the deviation.
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Radiagreen RA
- Physical state: Yellow to amber liquid
- Analytical purity: Unknown
- Lot/batch No.: OE70125
- Expiration date of the lot/batch: 25 January 2011
- Stability under test conditions: Stable
- Storage condition of test material: In refrigerator (2-8ºC) in the dark

Method

Target gene:
- S. typhimurium: Histidine gene
- E. coli: Tryptophan gene
Species / strain
Species / strain / cell type:
bacteria, other: Salmonella typhimurium (TA1535, TA1537, TA98 and TA100) and Escherichia coli (WP2uvrA).
Metabolic activation:
with and without
Metabolic activation system:
rat liver S9-mix induced by a combination of phenobarbital and ß-naphthoflavone
Test concentrations with justification for top dose:
Concentration range in the main test (with metabolic activation): 33, 100, 333, 1000 and 3330 µg/plate
Concentration range in the main test (without metabolic activation): 33, 100, 333, 1000 and 3330 µg/plate
Vehicle / solvent:
Solvent: Dimethyl sulfoxide
Controlsopen allclose all
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
Positive controls:
yes
Remarks:
for TA1535
Positive control substance:
sodium azide
Remarks:
Migrated to IUCLID6: without S9-mix
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
Positive controls:
yes
Remarks:
for T1537
Positive control substance:
9-aminoacridine
Remarks:
Migrated to IUCLID6: without S9-mix
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
Positive controls:
yes
Remarks:
for TA98
Positive control substance:
2-nitrofluorene
Remarks:
Migrated to IUCLID6: without S9-mix
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
Positive controls:
yes
Remarks:
for TA100
Positive control substance:
methylmethanesulfonate
Remarks:
Migrated to IUCLID6: without S9-mix
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
Positive controls:
yes
Remarks:
for WP2uvrA
Positive control substance:
4-nitroquinoline-N-oxide
Remarks:
Migrated to IUCLID6: without S9-mix
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
Positive controls:
yes
Remarks:
for all strains with S9-mix
Positive control substance:
other: 2-Aminoanthracene

Results and discussion

Test resultsopen allclose all
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
(> 333 µg/plate)
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity, but tested up to precipitating concentrations
Remarks:
from 1000 µg/plate and upwards
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
(> 333 µg/plate)
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity, but tested up to precipitating concentrations
Remarks:
seen at 3330 µg/plate
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
Observations:
All bacterial strains showed negative responses over the entire dose range, i.e. no significant dose-related increase in the number of revertants in two independently repeated experiments. The negative and strain-specific positive control values were within our laboratory historical control data ranges indicating that the test conditions were adequate and that the metabolic activation system functioned properly.
Remarks on result:
other: other: preliminary test
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Comments:
The negative and strain-specific positive control values
were within our laboratory historical control data ranges
indicating that the test conditions were adequate and that
the metabolic activation system functioned properly.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative with and without metabolic activation

All bacterial strains showed negative responses over the entire dose range, i.e. no significant dose-related increase in the number of revertants in two independently repeated experiments.