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EC number: 448-100-7 | CAS number: 70441-63-3
- 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
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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:
- 06 Jul - 27 Aug 1993
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Remarks:
- Fifth strain (E. coli WP2 or S. typhimurium TA102) is missing. However, based on the results of the present study the test substance is considered mutagenic. Additional testing with a fifth strain (WP2uvrA or TA 102) will not provide relevant information for the hazard and risk assessment of the substance. Therefore, this study is considered sufficient for hazard assessment purposes of the test substance.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 993
- Report date:
- 1993
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- Adopted in 1983
- Deviations:
- yes
- Remarks:
- Fifth strain (E. coli WP2 or S. typhimurium TA102) is missing. The present study was conducted in accordance with the previous version of the OECD TG 471. This deviation does not affect the final outcome of the study, nor will further testing.
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- -
- EC Number:
- 448-100-7
- EC Name:
- -
- Cas Number:
- 70441-63-3
- Molecular formula:
- C9H12FN
- IUPAC Name:
- 4-fluoro-N-(propan-2-yl)aniline
- Test material form:
- liquid
Constituent 1
Method
- Target gene:
- his operon
Species / strain
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Metabolic activation system:
- Cofactor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of rats treated with Aroclor 1254.
- Test concentrations with justification for top dose:
- Concentration range of the first experiment (with and without metabolic activation): 8, 40, 200, 1000, and 5000 µg/plate, all strains
Concentration range of the second experiment (with and without metabolic activation): 60, 120, 240, 480, and 960 µg/plate , all strains
Concentration range of the third experiment (with metabolic activation): 400, 600, 800, 1000, 1200, and 1400 µg/plate, TA 1537 and TA 98
Concentration range of the fourth experiment (with and without metabolic activation): 60, 120, 240, 480, and 960 µg/plate, TA 100 - Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: DMSO
Controls
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- other: Nitrofurantoin (NF, 0.2 µg/plate, -S9, TA 100); 4-Nitro-1,2-phenylene diamine (4-NPDA, 10 µg/plate, -S9, TA1537); 4-Nitro-1,2-phenylene diamine (4-NPDA, 0.5 µg/plate, -S9, TA98); 2-aminoanthracene (2-AA, 3 µg/plate, +S9, all strains, S9 activity control)
- Details on test system and experimental conditions:
- NUMBER OF REPLICATIONS:
- Number of cultures per concentration: 4
- Number of independent experiments: 4
METHOD OF TREATMENT/ EXPOSURE:
- Test substance added in agar (plate incorporation).
TREATMENT AND HARVEST SCHEDULE:
- Exposure duration/duration of treatment: 48 hours
- Harvest time after the end of treatment (sampling/recovery times): The count was made after the plates had been incubated for 48 hours at 37 °C.
METHODS FOR MEASUREMENT OF CYTOTOXICITY :
- Methods: 1) Background growth inhibition; 2) Toxic effect of the test substance was assumed when there was a marked and dose-dependent reduction in the mutant count per plate, compared to the negative control; 3) The titer was determined. Total bacterial counts were taken on two plates for each tested concentration.
METHODS FOR MEASUREMENTS OF GENOTOXICIY :
Colony count using automatic counter. - Evaluation criteria:
- The following criteria determined the acceptance of an assay:
1) The negative controls had to be within the expected range, as defined by published data (e.g. Maron and Ames, 1983) and the laboratories' own historical data.
2) The positive controls had to show sufficient effects, as defined by the laboratories' experience.
3) Titer determinations had to demonstrate sufficient bacterial density in the suspension.
An assay which did not comply with at least one of the above criteria was not used for assessment. Furthermore, the data generated in this assay needed to be confirmed by two additional independent experiments. Even if the criteria for points 1) - 3) were not met, an assay was accepted if it showed mutagenic activity of the test compound.
Assessment Criteria:
A reproducible and dose-related increase in mutant counts of at least one strain is considered to be a positive result.
For TA 1535, TA 100 and TA 98 this increase should be about twice that of negative controls, whereas for TA 1537, at least a threefold increase should be reached. Otherwise, the result is evaluated as negative. However, these guidelines may be overruled by good scientific judgement.
In case of questionable results, investigations should continue, possibly with modifications, until a final evaluation is possible. - Statistics:
- Mean values and standard deviation were calculated.
Results and discussion
Test resultsopen allclose all
- Key result
- Species / strain:
- S. typhimurium TA 1535
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- ≥960 µg/plate
- 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
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- ≥960 µg/plate
- 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 100
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- ≥1000 µg/plate
- 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 100
- Metabolic activation:
- with
- Genotoxicity:
- ambiguous
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- ≥1000 µg/plate
- 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 1537
- Metabolic activation:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- ≥960 µg/plate
- 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 1537
- Metabolic activation:
- with
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- ≥960 µg/plate
- 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:
- without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- ≥1400 µg/plate
- 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
- Genotoxicity:
- positive
- Remarks:
- ≥200 µg/plate
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- ≥1400 µg/plate
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not examined
- True negative controls validity:
- not examined
- Positive controls validity:
- valid
- Additional information on results:
- HISTORICAL CONTROL DATA
- Positive historical control data: The mean values of the positive controls of the present experiment were within the laboratories' historical control data range.
- Negative (solvent/vehicle) historical control data: The mean values of the DMSO vehicle control of the present experiment were within the laboratories' historical control data range. - Remarks on result:
- other: In the present study, the test item showed bacterial mutagenicity in the Salmonella typhimurium strain TA 98 in presence of S9 mix; allover the test substance was highly cytotoxic in all strains.
Any other information on results incl. tables
Table 1. Ames Test: results of experiment 1 (plate incorporation)
With (+) or without (-) S9-Mix | Test substance concentration | Mean number of revertant colonies per plate | |||
(μg/plate) | mean of 4 plates ± SD | ||||
Base-pair substitution type | Frameshift type | ||||
TA 1535 | TA 100 | TA 1537 | TA 98 | ||
– | DMSO | 9 ± 3 | 68 ± 8 | 11 ± 1 | 23 ± 9 |
– | 8 | 5 ± 2 | 73 ± 7 | 8 ± 4 | 31 ± 16 |
– | 40 | 8 ± 2 | 71 ± 3 | 8 ± 3 | 21 ± 5 |
– | 200 | 11 ± 4 | 76 ± 6 | 8 ± 3 | 18 ± 2 |
– | 1000 | 10 ± 4 | 82 ± 17 | 11 ± 5 | 21 ± 5 |
– | 5000 | b | b | b | b |
Positive controls, -S9 |
Name | Na-azide | NF | 4-NPDA | 4-NPDA |
Concentrations (μg/plate) | 10 | 0.2 | 10 | 0.5 | |
Mean No. of colonies/plate (average of 4 ± SD) | 496 ± 35* | 240 ± 23* | 51 ± 4* | 49 ± 7* | |
+ | DMSO | 8 ± 2 | 78 ± 8 | 5 ± 2 | 27 ± 10 |
+ | 8 | 6 ± 1 | 80 ± 10 | 9 ± 3 | 32 ± 10 |
+ | 40 | 9 ± 2 | 75 ± 12 | 7 ± 2 | 28 ± 8 |
+ | 200 | 9 ± 3 | 78 ± 11 | 9 ± 3 | 111 ± 18* |
+ | 1000 | 9 ± 6 | 132 ± 28 | 17 ± 3 | 277 ± 61* |
+ | 5000 | b | b | b | b |
Positive control, +S9 |
Name | 2-AA | 2-AA | 2-AA | 2-AA |
Concentrations (μg/plate) | 3 | 3 | 3 | 3 | |
Mean No. of colonies/plate (average of 4 ± SD) | 85 ± 6* | 550 ± 150* | 217 ± 40* | 1467 ± 88* |
SD = standard deviation
Na-azide = sodium azide
NF = nitrofurantoin
4-NPDA = 4-nitro-1,2-phenylenediamine
2-AA = 2-aminoanthracene
b = bacteriotoxic effect
* = mutagenic effect
Table 2. Ames Test: results of experiment 2 (plate incorporation)
With (+) or without (-) S9-Mix | Test substance concentration | Mean number of revertant colonies per plate | |||
(μg/plate) | mean of 4 plates ± SD | ||||
Base-pair substitution type | Frameshift type | ||||
TA 1535 | TA 1001 | TA 1537 | TA 98 | ||
– | DMSO | 10 ± 4 | 13 ± 2 | 22 ± 4 | |
– | 60 | 10 ± 3 | 8 ± 2 | 21 ± 4 | |
– | 120 | 12 ± 4 | 8 ± 1 | 21 ± 6 | |
– | 240 | 14 ± 5 | 8 ± 2 | 27 ± 3 | |
– | 480 | 10 ± 5 | 6 ± 3 | 28 ± 7 | |
– | 960 | 10 ± 3 | 10 ± 3 | 29 ± 8 | |
Positive controls, -S9 |
Name | Na-azide | 4-NPDA | 4-NPDA | |
Concentrations (μg/plate) | 10 | 10 | 0.5 | ||
Mean No. of colonies/plate (average of 4 ± SD) | 475 ± 45* | 48 ± 16* | 56 ± 18* | ||
+ | DMSO | 15 ± 3 | 14 ± 3 | 34 ± 7 | |
+ | 60 | 10 ± 4 | 13 ± 4 | 42 ± 10 | |
+ | 120 | 13 ± 5 | 10 ± 2 | 51 ± 9 | |
+ | 240 | 10 ± 1 | 10 ± 2 | 56 ± 9* | |
+ | 480 | 15 ± 2 | 10 ± 4 | 79 ± 10* | |
+ | 960 | 15 ± 2 | 11 ± 4 | 81 ± 11* | |
Positive control, +S9 |
Name | 2-AA | 2-AA | 2-AA | |
Concentrations (μg/plate) | 3 | 3 | 3 | ||
Mean No. of colonies/plate (average of 4 ± SD) | 188 ± 36* | 109 ± 13* | 1012 ± 90* |
SD = standard deviation
1 = not used for assessment beacause of low vehicle control counts
Na-azide = Sodium azide
4-NPDA = 4-Nitro-1,2-phenylenediamine
2-AA = 2-Aminoanthracene
* = mutagenic effect
Table 3. Ames Test: results of experiment 3 (plate incorporation)
With (+) S9-Mix | Test substance concentration | Mean number of revertant colonies per plate | |
(μg/plate) | mean of 4 plates ± SD | ||
Frameshift type | |||
TA 1537 | TA 98 | ||
+ | DMSO | 6 ± 4 | 18 ± 2 |
+ | 400 | 12 ± 5 | 47 ± 12* |
+ | 600 | 9 ± 3 | 70 ± 20* |
+ | 800 | 10 ± 3 | 64 ± 9* |
+ | 1000 | 11 ± 6 | 49 ± 13* |
+ | 1200 | 12 ± 2 | 78 ± 11* |
+ | 1400 | 12 ± 4 | 95 ± 12* |
Positive control, +S9 |
Name | 2-AA | 2-AA |
Concentrations (μg/plate) | 3 | 3 | |
Mean No. of colonies/plate (average of 4 ± SD) | 191 ± 42* | 648 ± 44* |
SD = standard deviation
2-AA = 2-Aminoanthracene
* = mutagenic effect
Table 4. Ames Test: results of experiment 4 (plate incorporation)
With (+) or without (-) S9-Mix | Test substance concentration | Mean number of revertant colonies per plate |
(μg/plate) | mean of 4 plates ± SD | |
Base-pair substitution type | ||
TA 100 | ||
– | DMSO | 95 ± 16 |
– | 60 | 107 ± 23 |
– | 120 | 104 ± 16 |
– | 240 | 104 ± 14 |
– | 480 | 114 ± 1 |
– | 960 | 132 ± 13 |
Positive controls, -S9 |
Name | NF |
Concentrations (μg/plate) | 0.2 | |
Mean No. of colonies/plate (average of 4 ± SD) | 262 ± 40* | |
+ | DMSO | 144 ± 20 |
+ | 60 | 139 ± 11 |
+ | 120 | 142 ± 15 |
+ | 240 | 175 ± 21 |
+ | 480 | 196 ± 10 |
+ | 960 | 202 ± 18 |
Positive control, +S9 |
Name | 2-AA |
Concentrations (μg/plate) | 3 | |
Mean No. of colonies/plate (average of 4 ± SD) | 1017 ± 76* |
SD = standard deviation
NF = nitrofurantoin
2-AA = 2-aminoanthracene
* = mutagenic effect
Applicant's summary and conclusion
- Conclusions:
- Under the conditions of the present Ames test conducted with 4 strains of Salmonella typhimurium (TA 1535, TA 100, TA 1537, and TA 98), a clear positive result indicating mutagenicity is reported for S. typhimurium TA 98, in the presence of metabolic activation.
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