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EC number: 807-019-0 | CAS number: 1231930-33-8
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Genetic toxicity: in vitro
Administrative data
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 14 October 2013 to 1 November 2013
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 013
- Report date:
- 2013
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- This assay design was based on OECD Guideline 471 (OECD, 1997)
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- 6-bromo-4-fluoro-2-methyl-1-(propan-2-yl)-1H-1,3-benzodiazole
- EC Number:
- 807-019-0
- Cas Number:
- 1231930-33-8
- Molecular formula:
- C11H12BrFN2
- IUPAC Name:
- 6-bromo-4-fluoro-2-methyl-1-(propan-2-yl)-1H-1,3-benzodiazole
Constituent 1
- Specific details on test material used for the study:
- - Source and lot/batch No.of test material: RS0-H71422-089- Storage condition of test material: Ambient temperature protected from light- Analytical purity: 99.4%
Method
- Target gene:
- Mutation of the uvrA gene (E. coli) or the uvrB gene (Salmonella)
Species / strain
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
- Additional strain / cell type characteristics:
- DNA polymerase A deficient
- Metabolic activation:
- with and without
- Metabolic activation system:
- Arochlor 1254-induced rat liver S9 fraction
- Test concentrations with justification for top dose:
- The test material was evaluated in the mutagenicity assay at doses of 1.60, 5.00, 16.0, 50.0, 160, 500, 1600, and 5000 micrograms/plate with and without S9
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: Dose formulations of the test material and dimethyl sulfoxide were prepared on the day of use - Justification for choice of solvent/vehicle: The volume of Dimetyl Sulfoxide used has been shown not to effect survival or induce mutations in control cultures
Controlsopen allclose all
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- benzo(a)pyrene
- Remarks:
- Tester Strain TA98 with S9 activation
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoanthracene
- Remarks:
- Tester Strains TA100, TA1535, TA1537 and WP2uvrA with S9 activation
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 2-nitrofluorene
- Remarks:
- Tester Strain TA98 without S9 activitation
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- Remarks:
- Tester Strain TA100 and TA1535 without S9 activitation
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: ICR-191
- Remarks:
- Tester Strain TA1537 without S9 activitation
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 4-nitroquinoline-N-oxide
- Remarks:
- WP2uvrA without S9 activitation
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: Plate incorporation method - the tester strain, test article, and S9 mix (where appropriate) are combined in molten top agar, which is then overlaid onto a minimal bottom agar plate. Following incubation, revertant colonies are counted.DURATION: Plates are incubated for 48 hours at 37oCSELECTION AGENT (mutation assays): Bacterial reverse mutation assayNUMBER OF REPLICATIONS: All test and control articles were evaluated in triplicate platesDETERMINATION OF CYTOTOXICITY: Cytotoxicty is indicated by the presence of "pinpoint" colonies and the absence of background lawn.
- Rationale for test conditions:
- The bacterial reverse mutation assay has been shown to be a sensitive, rapid, and accurate indicator of the mutagenic activity of many materials including a wide range of chemical classes. By using several different tester strains, both base pair substitution and frameshift mutations can be detected. Salmonellaand E. coli strains used in this assay are histidine and tryptophan auxotrophs, respectively, by virtue of conditionally lethal mutations in the appropriate operons. When these histidine (his–) or tryptophan (trp–) dependent cells are exposed to the test article and grown under selective conditions (minimal media with a trace amount of histidine or tryptophan), only those cells which revert to histidine (his+) or tryptophan (trp+) independence are able to form colonies. Trace amounts of histidine or tryptophan added to the media allow all the plated bacteria to undergo a few cell divisions, which is essential for mutagenesis to be fully expressed. his+ or trp+ revertants are readily discernable as colonies against the limited background growth of his– or trp– cells.
- Evaluation criteria:
- VALID STUDY CRITERIAThe vehicle control (Dimethyl Sulphoxide ) must show a normal range of bacterial colonies for each bacterial strain and should be consistent with historical data. The positive controls Benzo{a}pyrene (BP), 2-aminoanthracene (2AA), 2 -nitrofluorene (2NF), sodium azide (SA), ICR-191 and 4-nitroquinoline-N-oxide must show a mutagenic response and should be consistent with historical data. In the absence of toxicity or precipitation, a maximum treatement concentration of 5000 mcg/plate is sufficiently high to support study validity.POSITIVE RESPONSE CRITERIATest substance is judged to have induced a positive response when a concentration -related increase in revertants is observed in which the number of revertants exceeds the control values by at least 2 -fold (strains TA98, TA100, and WP2uvrA) or at least 3 -fold (strains TA1535 or TA1537) for at least two successive test article concentrations. When the above criteria are met for only one concentration, the determination of a positive response will be made on the basis of scientific judgement relative to the quality of the concentration response finding.NEGATIVE RESPONSE CRITERIAA test article is considered to produce a negative response when the criteria for a positive response is not met and the conditions for a valid assay have been satisfied.
- Statistics:
- No statistical analysis was used
Results and discussion
Test resultsopen allclose all
- Species / strain:
- S. typhimurium TA 98
- 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 100
- 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:
- 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 1537
- 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:
- 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
- Additional information on results:
- In the mutagenicity assay, LSN2800269 was evaluated in all five tester strains at doses of 1.60, 5.00, 16.0, 50.0, 160, 500, 1600, and 5000 micrograms/plate in the presence and absence of S9. The mutagenicty assay was repeated with TA98 and TA1535 under conditions without S9 at the same dose levels. In both tests, all dose levels of the test article, as well as the concurrent positive and vehicle controls were evaluated in triplicate plates.In the initial test, a complete absence of background lawn growth and revertant colony formation in all strains with and without S9 metabolic activation was observed at the 5000 μg/plate treatment level. A decreasing trend in the mean number of revertant colonies initiating at 1600 μg/plate was also observed in TA100, TA1535 and WP2uvrA tested with S9, and in TA100, TA1537, and WP2uvrA tested without S9. Enhanced background lawn growth was observed at 1600 μg/plate in TA98, TA100, and TA1537 tested without S9. Collectively, these observations are indicative of treatment-related toxicity. An absence of revertant colony and background lawn was also noted with TA1535 at dose levels ≥50 μg/plate under conditions without S9 as well as with the TA98 positive control tested without S9. To confirm appropriate sensitivity with TA98 and TA1535 under conditions without S9, testing with these strains without S9 was repeated. In the repeat test, an absence of revertant colony formation at 5000 μg/plate and reduced colony counts and background lawn growth observed at 1600 μg/plate were observed confirming the toxicity results observed in the initial test and appropriate sensitivity with these TA98 and TA1535 tested without S9. There were no positive increases in the numbers of revertant colonies observed in either the initial or repeat test at any LSN2800269 dose level with any tester strain in the absence or presence of S9 metabolic activation. All vehicle control values were within acceptable ranges, and all criteria for a valid study were met
Applicant's summary and conclusion
- Conclusions:
- These results indicate that LSN2800269 is negative in the Bacterial Reverse Mutation Assay tested up to 5000 μg/plate with and without S9, and under the conditions of this protocol.
- Executive summary:
The objective of this study was to evaluate LSN2800269, for its ability to induce reverse mutations in Salmonella typhimurium tester strains TA98, TA100, TA1535, and TA1537, and Escherichia coli (E. coli) strain WP2uvrA in the presence or absence of an exogenous mammalian metabolic activation system (S9). LSN2800269 was evaluated in the mutagenicity assay in all five tester strains at dose levels of 1.60, 5.00, 16.0, 50.0, 160, 500, 1600, and 5000 micrograms/plate with and without S9. A repeat mutagenicty assay was conducted with TA98 and TA1535 without S9 at the same dose levels.
In the initial test, LSN2800269 treatment-related toxicity was evident at the 5000 micrograms/plate treatment level by a complete absence of background lawn growth and revertant colony formation in all strains with and without S9 metabolic activation. Toxicity may have also been indicated by a decreasing trend in the mean number of revertant colonies initiating at 1600 μg/plate in TA100, TA1535, and WP2uvrA tested with S9, and in TA100, TA1537 and WP2uvrA tested without S9. Furthermore, treatment-related toxicity was indicated by enhanced background lawn growth observed at 1600 micrograms/plate in TA98, TA100, and TA1537 tested without S9.
An absence of revertant colony and background lawn was also noted with TA1535 at dose levels ≥50 μg/plate under conditions without S9 as well as with the TA98 positive control tested without S9. To confirm appropriate sensitivity with TA98 and TA1535 under conditions without S9, testing with these strains without S9 was repeated. In the repeat test, the absence of revertant colony formation at 5000 μg/plate and reduced colony counts and background lawn growth observed at 1600 μg/plate confirmed the toxicity results observed in the initial test.
There were no positive increases in the numbers of revertant colonies observed in either the initial or repeat test at any LSN2800269 dose level with any tester strain in the absence or presence of S9 metabolic activation. All vehicle control values were within acceptable ranges, and all criteria for a valid study were met. These results indicate that LSN2800269 is negative in the Bacterial Reverse Mutation Assay tested up to 5000 μg/plate with and without S9, and under the conditions of this protocol.
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