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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:
other: the tested substance is the acid part of the compound
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2016

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
yes (incl. certificate)
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- KIT Code No.: K-2698- Supplier: Korea Chemicals Management Association (KCMA)- Lot No.: 080108C105- Purity: 96.87%- Molecular Weight: 326.54- Density: 1.0550 at 20 deg C- Date of Receipt: January 14, 2008- Quantities received: 3 kg- Appearance: Liquid- Life time: January 8, 2009- Storage Conditions: Room Temperature [Archives No.: KIT-401(106)]

Method

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:
- Species and cell type: Rat (Sprague Dawley strain), male, liver - Quantity: 5 % S9 mix induced with Aroclor 1254
Test concentrations with justification for top dose:
- TA 98: 23.44, 46.88, 93.75, 187.5, 375, 750, 1,500 μg/plate (-)
- TA 98: 5.86, 11.72, 23.44, 46.88, 93.75, 187.5, 375, 750, 1,500, 3,000 μg/plate (+)
- TA 100: 5.86, 11.72, 23.44, 46.88, 93.75, 187.5 μg/plate (-)
- TA 100: 23.44, 46.88, 93.75, 187.5, 375, 750 μg/plate (+)
- TA 1535: 5.86, 11.72, 23.44, 46.88, 93.75, 187.5 μg/plate (-)
- TA 1535: 23.44, 46.88, 93.75, 187.5, 375, 750 μg/plate (+)
- TA 1537: 5.86, 11.72, 23.44, 46.88, 93.75, 187.5 μg/plate (-)
- TA 1537: 23.44, 46.88, 93.75, 187.5, 375, 750 μg/plate (+)
- WP2uvrA: 5.86, 11.72, 23.44, 46.88, 93.75, 187.5 μg/plate (-)
- WP2uvrA: 23.44, 46.88, 93.75, 187.5, 375, 750, 1500 μg/plate (+)
Vehicle / solvent:
Dimethylsulfoxide
Controls
Untreated negative controls:
yes
Remarks:
Dimethylsulfoxide
Negative solvent / vehicle controls:
yes
Remarks:
Dimethylsulfoxide
Positive controls:
yes
Positive control substance:
other: 2-Nitrofluorene, Sodium azide, 9-Aminoacridine, 4-Nitroquinoline 1-oxide ,2-Aminoanthracene and Benzo(a)pyrene
Details on test system and experimental conditions:
- Number of replicated: 3 plates/dose - Dose range finding experiment was carried out using dose levels of 8, 40, 200, 1,000, 3,000 and 5,000 μg/plate both in the absence and in the presence of metabolic activation system.- Cytotoxicity: A preliminary toxicity test was performed to define the concentrations to be used for the mutagenicity study.
Evaluation criteria:
The assay was considered valid if the number of spontaneous revertant colonies in vehicle control plates falls within the normal range and the positive control chemicals induce significant increases in the number of mutagen-induced revertant colonies compared to vehicle control. It was judged to be positive if there was a concentration-related increase over the range tested and/or a reproducible increase at one or more concentrations in the number of revertant colonies per plate in at least one strain with or without the metabolic system. In addition, it was judged to have a toxic effect (antibacterial effect) when a clearing or diminution of background lawn, the appearance of micro-colonies, and/or thedecrease more than 50% in the number of colonies compared to that of vehicle control was observed.

Results and discussion

Test resultsopen allclose all
Key result
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:
≥375 μg/plate (+) (TA 100, TA 1535, TA 1537) ≥93.75 μg/plate (-) (TA 100, TA 1535, TA 1537) ≥1500 μg/plate (+) (TA 98) ≥375 μg/plate (-) (TA 98)
Key result
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
≥750 μg/plate (+) (WP2 uvr ) 1500 μg/plate (+) (WP2 uvr )

Any other information on results incl. tables

Bacterial tests

A bacterial reverse mutation test was performed in accordance with [OECD TG 471] using Salmonella typhimurium (strains TA98,TA100, TA1535 and TA 1537) and Escherichia coli (strain WP2uvrA) with and without a metabolic activation system. Test doses were as follows:

 

5.86, 11.72, 23.44, 46.88, 93.75, 187.5, 375, 750, 1,500, 3,000μg/plate (+/-)

 

 

 

Dimethylsulfoxide (DMSO) was used as a vehicle and Sodium azide (SA), 2-Nitrofluorene (2-NF), 9-Aminoacridine (9-AA), 4-Nitroquinoline 1-oxide (4NQO),2-Aminoanthracene (2-AA)andBenzo(a)pyrene (BP)were used as positive control item.In all strains used, there was no increase in the number of revertant colonies compared to the vehicle control at any concentration of the acid part either in the presence or absence of metabolic activation system. However, in the first and second experiment, it was observed a clearing or diminution of background lawn, the appearance of micro-colonies, and/or more than 50% decrease in the number of colonies at more than 375 μg/plate and 93.75 μg/plate in TA100, TA1535 and TA1537 strains in the presence and absence of S9 activation, respectively. Also, in TA98 strain, it was observed a clearing or diminution of background lawn, the appearance of micro-colonies, and/or more than 50% decrease in the number of colonies at more than 1500 μg/plate and 375μg/plate in the presence and absence of S9 activation, respectively. InE. coliWP2uvrA strain, the more than 50% decrease in the number of colonies was observed at more than 750μg/plate and at 1500 μg/plate in the presence of S9 activation in the first and second experiment, respectively. The positive controls induced a significant increase in the numbers of revertant colonies indicating the assay was valid.

 

Applicant's summary and conclusion

Conclusions:
Interpretation of results: negative

In the presence and absence of metabolic system, no mutation in the Salmonella typhimurium (strains TA 98, TA 100, TA 1535 and TA 1537) and Escherichia coli (strain WP2 uvrA) occurred with the acid .