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EC number: 257-884-8 | CAS number: 52372-36-8
Genetic toxicity: in vitro
Administrative data
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1998
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 998
- Report date:
- 1998
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 472 (Genetic Toxicology: Escherichia coli, Reverse Mutation Assay)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- 3-(diethylamino)-7-oxo-7H-[1]benzopyrano[3',2':3,4]pyrido[1,2-a]benzimidazole-6-carbonitrile
- EC Number:
- 257-884-8
- EC Name:
- 3-(diethylamino)-7-oxo-7H-[1]benzopyrano[3',2':3,4]pyrido[1,2-a]benzimidazole-6-carbonitrile
- Cas Number:
- 52372-36-8
- Molecular formula:
- C23H18N4O2
- IUPAC Name:
- 17-(diethylamino)-11-oxo-14-oxa-3,10-diazapentacyclo[11.8.0.0²,¹⁰.0⁴,⁹.0¹⁵,²⁰]henicosa-1(21),2,4,6,8,12,15(20),16,18-nonaene-12-carbonitrile
- Test material form:
- solid: particulate/powder
- Details on test material:
- Disperse Red 362
Constituent 1
Method
Species / strain
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
- Metabolic activation:
- with and without
- Metabolic activation system:
- rat liver homogenate
- Test concentrations with justification for top dose:
- First experiment 25, 125, 625, 3125 and 6250 µg/plate - all strains
Second experiment: 4, 20, 100, 500 and 1000 µg/plate - TA 100 - Vehicle / solvent:
- Acetonitril
Controlsopen allclose all
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoanthracene
- Remarks:
- all strains with S9
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: N-methyl-N-nitro-N-nitrosoguanidine
- Remarks:
- TA1535, TA100 w/o S9
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 4-nitro-o-phenylendiamine
- Remarks:
- TA98 w/o S9
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- Remarks:
- TA1537 w/o S9
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- N-ethyl-N-nitro-N-nitrosoguanidine
- Remarks:
- E. coli WP2 uvrA w/o S9
- Details on test system and experimental conditions:
- METHOD OF APPLICATION:
1. Plate incorporation
- Incubation: 37°C 48 to 72 hours
- Triplicate plating
DETERMINATION OF CYTOTOXICITY
- decrease in number of revertants
- clearing or diminuation of background lawn
- reduction of titer - Evaluation criteria:
- Positive: dose-related and reproducible increase in number of revertant colonies
- doubling of spontaneous mutation rate in at least one tester strains either with or without S9
Negative: number of revertants are within historical negative control range in two independent experiments
Results and discussion
Test resultsopen allclose all
- Species / strain:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with
- Genotoxicity:
- positive
- Remarks:
- at precipitating concentrations
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with
- Genotoxicity:
- positive
- Remarks:
- precipitation from 625 µg/plate onwards
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with
- Genotoxicity:
- positive
- Remarks:
- at precipitating concentrations
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with
- Genotoxicity:
- positive
- Remarks:
- precipitation from 500 µg/plate onwards
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: from 500 µg/plate onwards
Applicant's summary and conclusion
- Conclusions:
- The test substance is mutagenic in the Salmonella typhimurium reverse mutation assay under the experimental conditions chosen here.
- Executive summary:
The test substance was tested for its mutagenic potential based on the ability to induce mutations in selected loci of several bacterial strains, i.e. Salmonella typhimurium and Escherichia coli, in a reverse mutation assay.The tester strains Salmonella typhimurium TA 1535, TA 100, TA 1537, TA 98 and E.coli WP2 uvrA were used in the standard plate test.
Dose ranges from 25 to 6250 µg/plate were used in all strains in the first experiment and 4 to 1000 µg/plate in TA 100 in the second experiment with and without metabolic activation.
Solubility: Precipitation of the test substance was found from about 500 µg/plate onwards
Toxicity: A slight decrease in the number of revertants was observed from about 3125 µg/plate onwards
Mutagenicity: An increase in the number of his revertants was observed after the addition of a metabolizing system using the strains TA 1535, TA 100, TA 1537 and TA 98.
Conclusion: According to the results of the present study, the test substance is mutagenic in the Salmonella typhimurium reverse mutation assay under the experimental conditions chosen here.
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