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EC number: 888-364-4 | CAS number: 146569-48-4
- 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
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- 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 mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 27 August 2021 to 20 December 2021
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 021
- Report date:
- 2021
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Version / remarks:
- adopted on 29th July 2016
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- in vitro mammalian cell gene mutation test using the Hprt and xprt genes
Test material
- Reference substance name:
- niobium trivanadium decamolybdenum tellurium dotetracontaoxide
- EC Number:
- 888-364-4
- Cas Number:
- 146569-48-4
- Molecular formula:
- Mo10V3Nb1Te1O42
- IUPAC Name:
- niobium trivanadium decamolybdenum tellurium dotetracontaoxide
- Test material form:
- solid
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
-Batch No.of test material:EX.14402.600
- Expiration date of the lot/batch:No change of properties know over time (endless)
[Unlimited shelf-life (no changes of properties over time known)]
- Purity test date:87.6 %
STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Ambient (21 to 29ºC)
- Solubility of test substance in the vehicle: Distilled water
- Reactivity of the test substance with the vehicle of the cell culture medium: NA
Method
- Target gene:
- HPRT
Species / strain
- Species / strain / cell type:
- Chinese hamster Ovary (CHO)
- Remarks:
- AA8
- Details on mammalian cell type (if applicable):
- CELLS USED
- Source of cells:American Type Culture Collection (ATCC)
- Cell doubling time:Approximately 12 hours
MEDIA USED
Type and identity of media including CO2 concentration if applicable: Alpha MEM CULTURE
MEDIA with 10% FBS and 1% penstrep and 5±1% CO2
- Properly maintained: [yes]
- Periodically checked for Mycoplasma contamination: [yes]
- Doubling time model chromosome number cells were checked.
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 homogenate
- Test concentrations with justification for top dose:
- 0.125, 0.25, 0.5 and 1 mg/mL.
• Since the test item did not precipitate at 0.03125, 0.0625, 0.125, 0.25 and 0.5 mg/mL, moderate precipitation was observed at 1 mg/mL and heavy precipitations was observed at 2 mg/mL. Hence, 1 mg/mL was considered as the highest concentration in the initial cytotoxicity test.
• At a concentration of 1 mg/mL, the Relative Survival was greater than 10%. Therefore 1 mg/mL was selected as the highest concentration for testing in gene mutation test.
• Based on the results of initial cytotoxicity test, four concentrations i.e. 0.125, 0.25, 0.5 and 1 mg/mL were selected for gene mutation test. - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: Distilled water
- Justification for choice of solvent/vehicle: found soluble in distilled water at 200 mg/mL
Controls
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 4-nitroquinoline-N-oxide
- benzo(a)pyrene
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
- Cell density at seeding (if applicable): 2×107METHOD OF APPLICATION: in medium
- Cell density at seeding (if applicable): 2×107
DURATION
- Exposure duration: 3 hours and 1 minute
- Expression time (cells in growth medium): 8 days for mutant phenotype expression
- Selection time (if incubation with a selection agent):7 days
SELECTION AGENT (mutation assays):10 μM of 6-Thioguanine
STAIN : 5% giemsa
NUMBER OF REPLICATIONS:5
METHODS STAINING TECHNIQUE USED: Post incubation period, medium from each culture flask
was aspirated and stained with 5% Giemsa stain. Number of colonies formed was counted manually.
DETERMINATION OF CYTOTOXICITY
- Method:cloning efficiency - Rationale for test conditions:
- Rationale for test conditions
Acceptance of a test is based on the following criteria:
•The concurrent vehicle control is considered acceptable for addition to the laboratory historical vehicle control database as described in OECD guidelines for testing of chemicals, No. 476.
•Concurrent positive controls should induce responses that are compatible with those generated in the historical positive control data base and produce a statistically significant increase compared with the concurrent negative/vehicle control.
•Two experimental conditions (i.e. with and without metabolic activation) were tested unless one resulted in positive results.
•Adequate number of cells and concentrations are analysable (according to OECD guidelines for testing of chemicals, No. 476).
•The criteria for the selection of top concentration are consistent with those described in OECD guidelines for testing of chemicals, No. 476. - Evaluation criteria:
- Colony counts in selective media and non-selective media
- Statistics:
- yes, Statistical analysis of the experimental data was carried out using SPSS Statistical package version 22.0.
Results and discussion
Test results
- Key result
- Species / strain:
- Chinese hamster Ovary (CHO)
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- True negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: No change in pH was observed in any of the test concentrations
- Water solubility: yes
- Precipitation: Precipitation test was conducted at 0.03125, 0.0625, 0.125, 0.25, 0.5, 1 and 2 mg/mL to determine the ability of the test item to cause precipitation in the medium. 100 µL of test item (3.125, 6.25, 12.5, 25, 50, 100 and 200 mg/mL) was mixed with 10 mL of culture media and incubated at 37±1ºC with 5±1% CO2 for 3 hours and 30 minutes. Post incubation, results were recorded for change in pH and signs of precipitation.
RANGE-FINDING: yes
HISTORICAL CONTROL DATA (with ranges, means and standard deviation and confidence interval (e.g. 95%)
- Positive historical control data: Yes
Positive Control- Benzo(a)pyrene and 4- Nitroquinoline N-oxide
With Metabolic Activation
(3 to 6 hours)
[Benzo(a)pyrene] Without Metabolic Activation
(3 to 6 hours)
[4 Nitroquinoline N-oxide]
Mean Data of Mutant Frequency/2x106 Cells 261.94 264.60
Standard
Deviation 27.28 18.52
Margin of Error 17.82 12.10
Upper bound 279.76 276.70
Lower bound 244.12 252.50
ADDITIONAL INFORMATION ON CYTOTOXICITY:
- Measurement of cytotoxicity used: Relative survivality
Any other information on results incl. tables
TABLE 1. SUMMARY OF INITIAL CYTOTOXICITY TEST
Set No. | Treatment | Concentration (mg/mL) | Average Colony Count ± SD | Cloning Efficiency (CE) | Adjusted Cloning Efficiency (ACE) | Relative Survival (RS) (%) | ||
Set 1 +S9 | Vehicle Control (distilled water) | - | 185.33 | ± | 6.51 | 0.93 | 1.14 | - |
test item | 0.0625 | 184.00 | ± | 2.00 | 0.92 | 1.11 | 97.37 | |
0.125 | 183.33 | ± | 5.51 | 0.92 | 1.10 | 96.49 | ||
0.25 | 182.00 | ± | 6.00 | 0.91 | 1.08 | 94.74 | ||
0.5 | 169.67 | ± | 4.51 | 0.85 | 0.98 | 85.96 | ||
1 | 158.33 | ± | 2.52 | 0.79 | 0.79 | 69.30 | ||
Set 2 -S9 | Vehicle Control (distilled water) | - | 187.00 | ± | 6.08 | 0.94 | 1.15 | - |
test item | 0.0625 | 185.00 | ± | 4.58 | 0.93 | 1.13 | 98.26 | |
0.125 | 183.33 | ± | 3.06 | 0.92 | 1.10 | 95.65 | ||
0.25 | 182.33 | ± | 5.86 | 0.91 | 1.07 | 93.04 | ||
0.5 | 173.33 | ± | 6.11 | 0.87 | 1.00 | 86.96 | ||
1 | 157.00 | ± | 7.55 | 0.79 | 0.80 | 69.57 |
+S9: with metabolic activation; -S9: without metabolic activation;
Adjusted CE = CE × Number of cells at the end of treatment/number of cells at the beginning of treatment.
RS = Adjusted CE in treated culture/Adjusted CE in the vehicle control × 100.
CE = Number of colonies/Number of cells plated.
TABLE 2. SUMMARY OF PARALLEL CYTOTOXICITY TEST- GENE MUTATION TEST
Set No. | Treatment | Concentration (mg/mL) | Average Colony Count ± SD | Cloning Efficiency (CE) | Adjusted Cloning Efficiency (ACE) | Relative Survival (RS) (%) | ||
Set 1 +S9 | Vehicle Control (distilled water) | - | 189.67 | ± | 4.16 | 0.95 | 1.15 | - |
test item | 0.125 | 183.67 | ± | 5.51 | 0.92 | 1.09 | 94.78 | |
0.25 | 182.33 | ± | 3.06 | 0.91 | 1.07 | 93.04 | ||
0.5 | 172.33 | ± | 7.37 | 0.86 | 1.00 | 86.96 | ||
1 | 157.33 | ± | 9.07 | 0.79 | 0.78 | 67.83 | ||
Benzo(a)pyrene (Positive Control) | 3 µg/mL | 181.33 | ± | 6.81 | 0.91 | 1.09 | 94.78 | |
Set 2 | Vehicle Control (distilled water) | - | 188.00 | ± | 3.61 | 0.94 | 1.19 | - |
test item | 0.125 | 187.67 | ± | 1.53 | 0.94 | 1.13 | 94.96 | |
0.25 | 186.00 | ± | 3.61 | 0.93 | 1.10 | 92.44 | ||
0.5 | 176.33 | ± | 5.51 | 0.88 | 1.01 | 84.87 | ||
1 | 155.33 | ± | 5.03 | 0.78 | 0.79 | 66.39 | ||
4 Nitroquinoline N-oxide (Positive Control) | 1 µg/mL | 186.67 | ± | 3.06 | 0.93 | 1.11 | 93.28 |
+S9: with metabolic activation; -S9: without metabolic activation;
*Note: Cloning Efficiency = 200 cells plated for each replicate.
RS = Adjusted CE in treated culture/Adjusted CE in the vehicle control × 100.
CE = Number of colonies/Number of cells plated.
Adjusted CE = CE × Number of cells at the end of treatment/number of cells at the beginning of treatment.
TABLE 3. SUMMARY OF GENE MUTATION TEST
Set No. | Treatment | Concentration (mg/mL) | *Average Colony Count ± SD | Cloning Efficiency in selective media | Cloning Efficiency in non-selective media* | Total number of Mutant Colonies/ 2×106cells | Mutant Frequency/ 2×106cells | ||
Set 1 +S9 | Vehicle Control (distilled water) | - | 188.33 | ± | 3.79 | 0.0000122 | 0.94 | 23 | 24.47 |
test item | 0.125 | 187.33 | ± | 7.02 | 0.0000122 | 0.94 | 23 | 24.47 | |
0.25 | 187.00 | ± | 2.65 | 0.0000117 | 0.94 | 22 | 23.40 | ||
0.5 | 185.00 | ± | 5.29 | 0.0000124 | 0.93 | 23 | 24.73 | ||
1 | 184.00 | ± | 2.00 | 0.0000120 | 0.92 | 22 | 23.91 | ||
Benzo(a)pyrene (Positive Control) | 3 µg/mL | 186.33 | ± | 2.52 | 0.0001290 | 0.93 | 240 | 258.06** | |
Set 2 -S9 | Vehicle Control (distilled water) | - | 186.33 | ± | 2.08 | 0.0000124 | 0.93 | 23 | 24.73 |
test item | 0.125 | 186.00 | ± | 3.00 | 0.0000129 | 0.93 | 24 | 25.81 | |
0.25 | 185.00 | ± | 3.00 | 0.0000129 | 0.93 | 24 | 25.81 | ||
0.5 | 184.33 | ± | 1.53 | 0.0000125 | 0.92 | 23 | 25.00 | ||
1 | 183.67 | ± | 3.06 | 0.0000125 | 0.92 | 23 | 25.00 | ||
4 Nitroquinoline N-oxide (Positive Control) | 1 µg/mL | 185.67 | ± | 1.15 | 0.0001328 | 0.93 | 247 | 265.59** |
+S9: with metabolic activation; -S9: without metabolic activation; *:Note: Cloning efficiency = 200 cells plated for each replicate.
**: Statistically significant (p˂0.05).
Mutant Frequency = Cloning efficiency of mutant colonies in selective medium/Cloning efficiency in non- selective medium.
Applicant's summary and conclusion
- Conclusions:
- Based on the results obtained, the test item is considered as non-mutagenic at and up to the concentration of 1 mg/mL, both in the presence and absence of metabolic activation under the tested laboratory conditions.
- Executive summary:
The test item was assessed for its potential to induce gene mutations at the Hprt locus of CHO AA8 cells of the Chinese Hamster.
The test item found soluble in distilled water at 200 mg/mL concentration. Post 3 hours of and 30 minutes of incubation, no precipitation was observed at the tested concentrations of 0.03125, 0.0625, 0.125, 0.25, 0.5 mg/mL, moderate precipitation was observed at 1 mg/mL, and heavy precipitation was observed at 2 mg/mL. No change in pH was observed in any of the test concentrations.
On the basis of precipitation results, 1 mg/mL was selected as the highest concentration for the initial cytotoxicity test. Initial cytotoxicity test was conducted at the concentrations of 0.0625, 0.125, 0.25, 0.5 and 1 mg/mL using distilled water as a vehicle in tetra plates/group in the presence and absence of metabolic activation (3 hours and 17 minutes). Cytotoxicity was assessed by determining the Adjusted Cloning Efficiency and Relative Survival in the test. The results of the initial cytotoxicity test indicated that the Relative Survival was greater than 10% (69.30 % in presence of metabolic activation and 69.57 % in absence of metabolic activation) at 1 mg/mL when compared with the respective vehicle control, both in the presence and absence of metabolic activation. Based on these results 1 mg/mL was selected as highest concentration for gene mutation test.
The gene mutation test was conducted at the concentrations 0.125, 0.25, 0.5 and 1mg/mL using distilled water as a vehicle in four plates/group in the presence and absence of metabolic activation (3 hours and 1 minute).
Benzo(a) pyrene and 4 Nitroquinoline N-oxide were used as positive controls for the gene mutation test.Cytotoxicity as Relative Survival was 67.83 % in presence of metabolic activation and66.39 % in absence of metabolic activationat the highest tested concentration of 1 mg/mL.
There was no statistically significant increase in mutant frequencies at any of the concentrations tested when compared with the vehicle control. Moreover, treatment with the test item resulted in mutant frequencies which fell within acceptable ranges with regard to historical controls.
There was statistically significant increase in mutant frequenciesfor positive controlswhen compared with the vehicle controlin both metabolic activation and absence of metabolic activation.
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