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EC number: 812-548-5 | CAS number: 1621424-03-0
- 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:
- 22 Oct 2019 - 27 Feb 2020
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Remarks:
- Only 2-aminoanthracene was used to test the efficacy of the S9-mix. Additional mutagens requiring metabolic activation such as benzo(a)pyrene or dimethylbenzanthracene were not used to characterise the S9-mix.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 020
- Report date:
- 2020
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- Adopted in 1997
- Deviations:
- yes
- Remarks:
- Only 2-aminoanthracene was used to test the efficacy of the S9-mix. Additional mutagens requiring metabolic activation such as benzo(a)pyrene or dimethylbenzanthracene were not used to characterise the S9-mix.
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Slovak National Accreditation Service, Bratislava, Slovak Republic
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- {[4-({dimethyl[3-(prop-2-enamido)propyl]azaniumyl}methyl)phenyl]methyl}dimethyl[3-(prop-2-enamido)propyl]azanium dichloride
- EC Number:
- 812-548-5
- Cas Number:
- 1621424-03-0
- Molecular formula:
- C24H40Cl2N4O2
- IUPAC Name:
- {[4-({dimethyl[3-(prop-2-enamido)propyl]azaniumyl}methyl)phenyl]methyl}dimethyl[3-(prop-2-enamido)propyl]azanium dichloride
Constituent 1
Method
- Target gene:
- his operon for S. typhimurium strains and trp operon for the E. coli strain
Species / strainopen allclose all
- Species / strain / cell type:
- S. typhimurium TA 97
- Species / strain / cell type:
- S. typhimurium TA 98
- Species / strain / cell type:
- S. typhimurium TA 100
- Species / strain / cell type:
- S. typhimurium TA 1535
- Species / strain / cell type:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Metabolic activation system:
- Type and composition of metabolic activation system:
- source of S9 : The mammalian liver post-mitochondrial fraction (S9) used for metabolic activation was prepared from Sprague Dawley male rats (Charles River, Velaz, Czech Republic). Animals were pre-treated with 20-methylcholanthrene (administered i.p. at 80 mg/kg bw) 5 days prior to killing.
- method of preparation of S9 mix: The S9 homogenate was diluted with co-factors: 33 mM KCl, 8 mM MgCl2, 5 mM, glucose-6-phosphate, 4 mM NADP, and 100 mM phosphate buffer (pH = 7.4) to obtain the S9-mix.
- concentration or volume of S9 mix and S9 in the final culture medium: The S9 concentration in the S9-mix was 10%. The volume of S9-mix in the final culture medium was 0.5 mL.
- quality controls of S9: The activity of S9 fraction was determined in bacterial reverse gene mutation test on Salmonella typhimurium strains TA98 and TA100. - Test concentrations with justification for top dose:
- Range-finding experiment: 50, 150, 500, 1500, 2500, and 5000 µg/plate, without metabolic activation, TA 100, TA 98
Main experiment: 50, 150, 500, 1500, 2500, and 5000 µg/plate, with and without metabolic activation, all strains
5000 µg/plate was selected as the highest test concentration based on the results of a range-finding experiment in which no cytotoxicity was observed up to and including the highest concentration. - Vehicle / solvent:
- - Vehicle used:
sterile deionised (purified) water
- Justification for choice of vehicle: The vehicle used did not affect the spontaneous mutation level and it is recommended for use in this test.
Controls
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- Remarks:
- water
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 4-nitroquinoline-N-oxide
- 9-aminoacridine
- 2-nitrofluorene
- sodium azide
- other: 2-aminoanthracene
- Details on test system and experimental conditions:
- NUMBER OF REPLICATIONS:
- Number of cultures per concentration: triplicate
- Number of independent experiments: single experiment
METHOD OF TREATMENT/ EXPOSURE:
- Cell density at seeding: 1E+09 cells/mL
- Test substance added in agar (plate incorporation).
TREATMENT AND HARVEST SCHEDULE:
- Exposure duration/duration of treatment: 48 – 72 h
METHODS FOR MEASUREMENT OF CYTOTOXICITY
- Method: background growth inhibition
METHODS FOR MEASUREMENTS OF GENOTOXICIY
After the incubation period, the number of revertant colonies per plate was counted by hand. The mutation frequency at each dose concentration level of the test substance was compared to the one observed in negative and positive controls. - Evaluation criteria:
- Considering biological relevance the test substance is considered positive if the assay is valid and the following conditions are met:
- Concentration-related increase over the tested range and reproducible increase at one or more concentrations in the number of revertant colonies per plate in at least one strain with or without metabolic activation.
- Mutation factor > 2.
A positive result indicates that the test substance induces mutations in Salmonella typhimurium or E.coli.
The test substance for which results do not meet the above criteria is considered non-mutagenic in this test.
Negative results indicate that under the reported test conditions, the test substance does not produce mutations in Salmonella typhimurium and E.coli. - Statistics:
- Mean values and standard deviation were calculated.
The mutation frequency (MF) at each tested concentration of the test substance was compared to the MF observed in negative and positive controls.
The statistical analysis was carried out using unpaired T-test.
Results and discussion
Test resultsopen allclose all
- Key result
- Species / strain:
- S. typhimurium TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- True negative controls validity:
- not examined
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- True negative controls validity:
- not examined
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 97
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- True negative controls validity:
- not examined
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- True negative controls validity:
- not examined
- Positive controls validity:
- valid
- Key result
- Species / strain:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- True negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- RANGE-FINDING/SCREENING STUDY
A range-finding assay to determine the optimal non-toxic test concentrations of FV-1295 was performed. Six concentrations of the test item (50, 150, 500, 1500, 2500, and 5000 µg/plate) were tested using Salmonella typhimurium test strains TA 100 and TA 98 without metabolic activation. No decrease in the number of revertant colonies was observed up to the highest tested concentration.
STUDY RESULTS
Ames test:
- Signs of toxicity: No signs of toxicity were noted in any strain up to and included the highest concentration tested, i.e 5000 µg/plate.
- Mean number of revertant colonies per plate and standard deviation: the mean number of revertant colonies was not significantly increased for any strains at any concentration tested. Please see Table 3 under "Any other information on results incl. tables".
HISTORICAL CONTROL DATA
In general, the results of the present study fall within the historical control data (HCD) range (Table 1 under "Any other information on results incl. tables"). For TA 100, with metabolic activation, mean levels of spontaneous mutations were slightly above the HCD range (252 revertants/plate, HCD range: 120 - 231 revertants/plate). For TA 98, with metabolic activation, mean levels of mutations induced by the positive control were above the HCD range (2417 revertants/plate, HCD range: 150 - 1644 revertants/plate). For WP2uvrA, with and without metabolic activation, mean levels of mutations induced by the positive control were above the HCD range (without S9: 1033 revertants/plate, HCD range: 82 - 912 revertants/plate; with S9: 855 revertants/plate, HCD range: 194 - 648 revertants/plate). Although the mean numbers of revertants per plate were increased, no increase was observed after treatment with the test substance. Therefore, these differences are not considered to affect the final outcome of the study.
Any other information on results incl. tables
Table 1: Historical negative and positive control values 2015 - 2019
Historical control data |
|||||||||
Revertants per plate |
|||||||||
|
Metabolic activation |
||||||||
without |
with |
||||||||
Mean |
SD |
Min |
Max | Mean | SD | Min | Max | ||
TA 100 | Neg | 189 | 37 | 112 | 272 | 177 | 30 | 120 | 231 |
TA 100 | Pos | 691 | 170 | 440 | 1148 | 1025 | 434 | 398 | 2888 |
TA 1535 | Neg | 22 | 8 | 6 | 43 | 23 | 8 | 11 | 43 |
TA 1535 | Pos | 615 | 171 | 336 | 964 | 193 | 127 | 34 | 604 |
TA 97 | Neg | 161 | 30 | 114 | 227 | 193 | 36 | 127 | 286 |
TA 97 | Pos | 1088 | 525 | 400 | 2776 | 870 | 367 | 370 | 1616 |
TA 98 | Neg | 24 | 7 | 12 | 43 | 35 | 11 | 19 | 85 |
TA 98 | Pos | 261 | 144 | 117 | 680 | 754 | 446 | 150 | 1644 |
WP2uvrA | Neg | 36 | 11 | 18 | 68 | 44 | 9 | 31 | 70 |
WP2uvrA | Pos | 377 | 268 | 82 | 912 | 387 | 136 | 194 | 648 |
SD = Standard deviation
Min = minimum value
Max = maximum value
Neg = negative control
Pos = positive control
Table 2: Results of dose range finding assay without metabolic activation
Without (-) S9-Mix | Test substance concentration | Mean number of revertant colonies per plate | |
(μg/plate) | (average of 3 plates ± Standard deviation) | ||
Base-pair substitution type | Frameshift type | ||
TA 100 | TA 98 | ||
- | vehicle (water) | 369 ± 24 | 19 ± 5 |
- | 50 | 370 ± 12 | 22 ± 5 |
- | 150 | 359 ± 9 | 20 ± 6 |
- | 500 | 345 ± 12 | 20 ± 4 |
- | 1500 | 371 ± 21 | 19 ± 2 |
- | 2500 | 369 ± 17 | 27 ± 2 |
- | 5000 | 373 ± 11 | 22 ± 2 |
Positive controls, -S9 |
Name | Na-azide | 2-NF |
Concentrations (μg/plate) | 1.5 | 3 | |
Mean No. of colonies/plate (average of 3 ± SD) | 1165* ± 84 | 117* ± 8 |
Na-azide = Sodium azide
2-NF = 2-nitrofluorene
* = p < 0.05
Table 3: Results of Ames test with FV-1295 (plate incorporation)
With (+) or without (-) S9-Mix | Test substance concentration | Mean number of revertant colonies per plate | ||||
(μg/plate) | (average of 3 plates ± Standard deviation) | |||||
Base-pair substitution type | Frameshift type | |||||
TA 100 | TA1535 | WP2uvrA | TA 98 | TA 97 | ||
- | vehicle (water) | 257 ± 11 | 22 ± 1 | 40 ± 3 | 18 ± 2 | 173 ± 20 |
- | 50 | 255 ± 10 | 25 ± 8 | 43 ± 5 | 21 ± 3 | 168 ± 25 |
- | 150 | 243 ± 13 | 20 ± 2 | 41 ± 7 | 19 ± 2 | 179 ± 34 |
- | 500 | 236 ± 11 | 24* ± 2 | 42 ± 7 | 18 ± 2 | 180 ± 25 |
- | 1500 | 251 ± 3 | 19 ± 3 | 40 ± 4 | 21 ± 3 | 174 ± 9 |
- | 2500 | 254 ± 15 | 18* ± 2 | 45 ± 5 | 19 ± 1 | 188 ± 22 |
- | 5000 | 247 ± 20 | 23 ± 4 | 42 ± 6 | 20 ± 5 | 185 ± 21 |
Positive controls, -S9 |
Name | Na-azide | Na-azide | 4-NQO | 2-NF | 9-AA |
Concentrations (μg/plate) | 1.5 | 1.5 | 5 | 3 | 75 | |
Mean No. of colonies/plate (average of 3 ± SD) | 891* ± 47 | 947* ± 113 | 1033* ± 70 | 177* ± 17 | 987* ± 49 | |
+ | vehicle (water) | 252 ± 9 | 19 ± 3 | 46 ± 3 | 20 ± 2 | 188 ± 30 |
+ | 50 | 258 ± 4 | 19 ± 1 | 52 ± 3 | 19 ± 1 | 189 ± 5 |
+ | 150 | 253 ± 7 | 18 ± 4 | 51 ± 2 | 22 ± 3 | 185 ± 9 |
+ | 500 | 255 ± 5 | 20 ± 4 | 51 ± 6 | 21 ± 2 | 188 ± 4 |
+ | 1500 | 256 ± 14 | 19 ± 2 | 50 ± 3 | 18 ± 1 | 180 ± 16 |
+ | 2500 | 253 ± 7 | 18 ± 2 | 49 ± 1 | 22 ± 3 | 175 ± 12 |
+ | 5000 | 257 ± 7 | 19 ± 4 | 52 ± 3 | 23 ± 4 | 177 ± 19 |
Positive controls, +S9 |
Name | 2-AA | 2-AA | 2-AA | 2-AA | 2-AA |
Concentrations (μg/plate) | 1 | 5 | 5 | 5 | 5 | |
Mean No. of colonies/plate (average of 3 ± SD) | 2692* ± 60 | 178* ± 15 | 855* ± 87 | 2417* ± 293 | 1007* ± 44 |
Na-azide = Sodium azide
4-NQO = 4-nitroquinoline-N-oxide
2-NF = 2-nitrofluorene
9-AA = 9-aminoacridine
2-AA = 2-Aminoanthracene
* = p < 0.05
Applicant's summary and conclusion
- Conclusions:
- Under the conditions of the present Ames test, the test substance FV-1295 was negative for genotoxicity with and without metabolic activation.
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