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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:
February 19, 2009 - June 19, 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP-guideline study: The study was conducted in accordance with hte following guidelines: OECD-guidelines for the testing of chemicals Part 471, adopted July 21, 1997 "Bacterial Reverse Mutation Test" and EU-Guideline B.13/14 adopted may 31, 2008 "Mutagenicity-Salmonella typhimurium reverse mutation assay"

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Target gene:
Five genetically manipulated strains of Salmonella typhimurium (TA 97a, TA 98, TA 100, TA 102 and TA 1535) were exposed to the test item.
plate incorboration method (first experiment)
pre-incubation method (second and third experiment)
Species / strainopen allclose all
Species / strain / cell type:
other: TA97a
Additional strain / cell type characteristics:
other: hisD6610, uvrB, pKM 101, rfa
Species / strain / cell type:
S. typhimurium TA 98
Additional strain / cell type characteristics:
other: hisD3052, uvrB, pKM 101, rfa
Species / strain / cell type:
S. typhimurium TA 100
Additional strain / cell type characteristics:
other: hisG46, uvrB, pKM 101, rfa
Species / strain / cell type:
S. typhimurium TA 102
Additional strain / cell type characteristics:
other: hisG428, pKM 101, rfa
Species / strain / cell type:
S. typhimurium TA 1535
Additional strain / cell type characteristics:
other: hisG46, uvrB, rfa
Metabolic activation:
with and without
Metabolic activation system:
S9
Test concentrations with justification for top dose:
First Experiment:
Five concentrations of the test item, dissolved in deionised water (ranging from 5014 to 50 µg/plate) were used.
concentrations tested: 5014/1504/501/150/50 µg/plate
Second Experiment:
To verify the results of the first experiment, a second experiment was performed, using five concentrations of the test item (ranging from 4999 to 312.5 µg/plate) and a modification in study performance (pre-incubation method).
Concentrations tested: 4999/2500/1250/625/312.5 µg/plate
Third Experiment:
To verify the results of the first experiment, a third experiment was performed, using five concentrations of the test item (ranging from 5004 to 312.5 µg/plate) and a modification in study performance (pre-incubation method).
Concentrations tested: 5004/2502/1251/625/312.5 µg/plate
Controlsopen allclose all
Untreated negative controls:
yes
Remarks:
water and DMSO (historical data of the laboratory)
Negative solvent / vehicle controls:
yes
Remarks:
water
True negative controls:
yes
Positive controls:
yes
Positive control substance:
other: 4-Nitro-1,2-phenylene diamine (Strains 97a, 98, 102)
Remarks:
without metabolic activation system
Untreated negative controls:
yes
Remarks:
water and DMSO (historical data of the laboratory)
Negative solvent / vehicle controls:
yes
Remarks:
water
True negative controls:
yes
Positive controls:
yes
Positive control substance:
sodium azide
Remarks:
without metabolic activation system Migrated to IUCLID6: Strains 100 and 1535
Untreated negative controls:
yes
Remarks:
water and DMSO (historical data of the laboratory)
Negative solvent / vehicle controls:
yes
Remarks:
water
True negative controls:
yes
Positive controls:
yes
Positive control substance:
benzo(a)pyrene
Remarks:
with metabolic activation system Migrated to IUCLID6: Strain 98
Untreated negative controls:
yes
Remarks:
water and DMSO (historical data of the laboratory)
Negative solvent / vehicle controls:
yes
Remarks:
water
True negative controls:
yes
Positive controls:
yes
Positive control substance:
other: 2-Aminoanthracene (Strains 97a, 100, 102, 1535)
Remarks:
with metabolic activation system

Results and discussion

Test results
Species / strain:
other: TA97a, TA98, TA100, TA102, TA1535
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
Remarks on result:
other: all strains/cell types tested

Any other information on results incl. tables

Solubility and Toxicity (all three experiments):

No signs of toxicity towards the tested strains could be observed. The backround lawn was visible an the number of revertant colonies was not reduced.

Mutagenicity (all three experiments):

No significant increase of the number of revertant colonies in the treatments with and without metabolic activation could be observed. No concentration-related increase over the tested range was found.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

The test item is not mutagenic in the Bacterial Reverse Mutation Test.