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EC number: 473-810-9 | CAS number: -
- 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:
- 31 May 2005 to 15 July 2005
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 005
- Report date:
- 2005
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- 1997
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- Version / remarks:
- 2000
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
Test material
- Reference substance name:
- -
- EC Number:
- 473-810-9
- EC Name:
- -
- Cas Number:
- 1480-96-2
- Molecular formula:
- Hill formula: C5H5FN2O2 CAS formula: C5H5FN2O2
- IUPAC Name:
- 5-fluoro-2-methoxy-3,4-dihydropyrimidin-4-one
- Test material form:
- solid: particulate/powder
- Details on test material:
- - Appearance: white powder
- Storage conditions of test material: at room temperature, protected from humidity and under nitrogen gas
Constituent 1
Method
- Target gene:
- - Histidine requirement in the Salmonella typhimurium strains (Histidine operon)
Species / strain
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Details on mammalian cell type (if applicable):
- CELLS USED
- Source of cells: The five strains of Salmonella typhimurium were supplied by B.N. Ames' Laboratory (University of California, Berkeley or Oakland Research Institute, USA)
MEDIA USED
- Type and identity of media: The day before treatment, cultures were inoculated from frozen permanents: a scrape was taken under sterile conditions and put into approximately 6 mL of nutrient broth. The nutrient broth was placed under agitation in an incubator at 37 °C for about 14 hours, to produce bacterial suspensions
- Properly maintained: Yes. The bacterial strains were stored in liquid nitrogen in cryoprotective medium (1 mL nutrient broth and 0.09 mL dimethylsulfoxide).
- Metabolic activation:
- with and without
- Metabolic activation system:
- S9 mix prepared from a liver microsomal fraction of rats induced with Aroclor 1254
- Test concentrations with justification for top dose:
- - Preliminary toxicity test (TA98, TA100 and TA102): 2, 20, 100, 200, 500 and 1000 µg/plate (with and without metabolic activation)
- Main mutagenicity test (all strains): 62.5, 125, 250, 500 and 1000 µg/plate (with and without metabolic activation) - Vehicle / solvent:
- - Solvent: Water for injections
- Justification for choice of solvent/vehicle: The vehicle was selected according to the results of solubility trials performed before the preliminary toxicity test. The test material was insoluble in dimethylsulfoxide, ethanol, acetone and tetrahydrofuran down to 10 mg/mL. It was poorly soluble in water and the limit of solubility was approximately 5 mg/mL. Before use, the vehicle was degassed by sonication for at least 15 minutes and then saturated with nitrogen gas and kept under nitrogen for at least 15 minutes.
Controls
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 9-aminoacridine
- 2-nitrofluorene
- sodium azide
- mitomycin C
- other: 2-Anthramine
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation); preincubation
The preliminary test, both experiments without S9 mix and the first experiment with S9 mix were performed according to the direct plate incorporation method. The second experiment with S9 mix was performed according to the preincubation method.
- Plate Incorporation Method: Test material solution (0.2 mL), S9 mix when required or phosphate buffer pH 7.4 (0.5 mL) and bacterial suspension (0.1 mL) were mixed with 2 mL of overlay agar (containing traces of the relevant amino acid and biotin and maintained at 45 °C). After rapid homogenisation, the mixture was overlaid onto a Petri plate containing minimum medium.
- Pre-Incubation Method: Test material solution (0.2 mL), S9 mix (0.5 mL) and the bacterial suspension (0.1 mL) were incubated for 60 minutes at 37 °C, under shaking, before adding the overlay agar and pouring onto the surface of a minimum agar plate.
DURATION
- Exposure duration: 48 to 72 hours of incubation at 37 °C
NUMBER OF REPLICATIONS: Testing was performed in triplicate
COLONY COUNTING: Revertants were scored with an automatic counter
DETERMINATION OF CYTOTOXICITY
- Method: The evaluation of the toxicity was performed on the basis of the observation of the decrease in the number of revertant colonies and/or a thinning of the bacterial lawn. - Evaluation criteria:
- ACCEPTANCE CRITERIA
The study was considered valid if the following criteria were fully met:
- The number of revertants in the vehicle controls is consistent with the historical data of the testing facility
- The number of revertants in the positive controls is higher than that of the vehicle controls and is consistent with the historical data of the testing facility.
EVALUATION CRITERIA
A reproducible 2-fold increase (for the TA 98, TA 100 and TA 102 strains) or 3-fold increase (for the TA 1535 and TA 1537 strains) in the number of revertants compared with the vehicle controls, in any strain at any dose-level and/or evidence of a dose-relationship was considered as a positive result. Reference to historical data or other considerations of biological relevance may also be taken into account in the evaluation of the data obtained.
Results and discussion
Test results
- Key result
- Species / strain:
- other: S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- PRELIMINARY TOXICITY TEST
No precipitate was observed in the Petri plates when scoring the revertants at any dose-level. No noteworthy toxicity was noted towards the three strains used, with and without S9 mix. The enhanced lawn observed with the TA 102 strain without S9 mix did not allow the scoring of revertants with this strain.
MUTAGENICITY EXPERIMENTS
The number of revertants for the vehicle and positive controls was as specified in the acceptance criteria. The study was therefore considered valid.
Since the test material was poorly soluble in the vehicle and non-toxic in the preliminary toxicity test, the highest dose-level for the main test was the maximum achievable dose-level, taking into account the limit of solubility in the vehicle and the maximum treatment volume used in the testing laboratory for the selected vehicle.
No precipitate was observed in the Petri plates when scoring the revertants at any dose-level. No toxicity was noted towards all the strains used, both with and without S9 mix.
The test material did not induce any noteworthy increase in the number of revertants, both with and without S9 mix, in any of the five strains.
Any other information on results incl. tables
Table 1: Summary of Experiment 1
± S9 Mix |
Concentration (µg/plate) |
Mean number of colonies/plate |
||||
Base-pair Substitution Type |
Frameshift Type |
|||||
TA100 |
TA1535 |
TA102 |
TA98 |
TA1537 |
||
- |
Solvent 62.5 125 250 500 1000 |
121 113 112 114 123 100 |
19 14 13 19 14 10 |
489 491 493 494 399 228 |
34 20 28 31 28 24 |
9 3 9 5 3 2 |
+ |
Solvent 62.5 125 250 500 1000 |
118 102 115 112 101 97 |
13 7 11 11 14 13 |
512 540 611 512 542 437 |
35 32 27 37 20 24 |
6 11 11 9 4 7 |
Positive Controls |
||||||
- |
Name |
NAN3 |
NAN3 |
MMC |
2NF |
9AA |
Concentration (µg/plate) |
1 |
1 |
0.5 |
0.5 |
50 |
|
Mean no. colonies/plate |
621 |
568 |
1320 |
267 |
1255 |
|
+ |
Name |
2AM |
2AM |
2AM |
2AM |
2AM |
Concentration (µg/plate) |
2 |
2 |
10 |
2 |
2 |
|
Mean no. colonies/plate |
1368 |
322 |
1650 |
1127 |
163 |
NAN3 = Sodium Azide
MMC = Mitomycin C
2NF = 2-Nitrofluorene
9AA = 9 -Aminoacridine
2AM = 2 -Anthramine
Table 2: Summary of Experiment 2
± S9 Mix |
Concentration (µg/plate) |
Mean number of colonies/plate |
||||
Base-pair Substitution Type |
Frameshift Type |
|||||
TA100 |
TA1535 |
TA102 |
TA98 |
TA1537 |
||
- |
Solvent 62.5 125 250 500 1000 |
117 119 123 137 125 107 |
18 15 14 15 14 13 |
301 256 242 228 200 144 |
31 17 18 14 11 15 |
5 6 6 7 6 2 |
+ |
Solvent 62.5 125 250 500 1000 |
135 138 140 110 146 133 |
12 19 13 11 13 14 |
375 324 377 278 296 325 |
16 23 28 21 22 27 |
7 9 7 10 10 4 |
Positive Controls |
||||||
- |
Name |
NAN3 |
NAN3 |
MMC |
2NF |
9AA |
Concentration (µg/plate) |
1 |
1 |
0.5 |
0.5 |
50 |
|
Mean no. colonies/plate |
491 |
497 |
1774 |
179 |
401 |
|
+ |
Name |
2AM |
2AM |
2AM |
2AM |
2AM |
Concentration (µg/plate) |
2 |
2 |
10 |
2 |
2 |
|
Mean no. colonies/plate |
1061 |
153 |
1977 |
1218 |
147 |
NAN3 = Sodium Azide
MMC = Mitomycin C
2NF = 2-Nitrofluorene
9AA = 9 -Aminoacridine
2AM = 2 -Anthramine
Applicant's summary and conclusion
- Conclusions:
- Under the conditions of this study, the test material was considered to be non-mutagenic.
- Executive summary:
The potential of the test material to cause mutagenic effects in bacteria was assessed in accordance with the standardised guidelines OECD 471 and EU Method B.13/14 under GLP conditions.
Five strains of Salmonella typhimurium were used, TA 1535, TA 1537, TA 98, TA 100 and TA 102. A preliminary toxicity test was performed to define the dose-levels to be used for the mutagenicity study. The test material was then tested in two independent experiments, with and without a metabolic activation system (S9 mix prepared from a liver microsomal fraction of rats induced with Aroclor 1254). Both experiments were performed according to the direct plate incorporation method except for the second test with S9 mix, which was performed according to the preincubation method.
The test material was poorly soluble in the vehicle (water) and non-toxic in the preliminary toxicity test, therefore the highest dose-level for the main test was the maximum achievable dose-level. The selected dose-levels were 62.5, 125, 250, 500 and 1000 μg/plate. Each strain was exposed to at least five dose-levels of the test material (three plates/dose-level). After 48 to 72 hours of incubation at 37 °C, the revertant colonies were scored.
The evaluation of the toxicity was performed on the basis of the observation of the decrease in the number of revertant colonies and/or a thinning of the bacterial lawn.
The number of revertants for the vehicle and positive controls was as specified in the acceptance criteria. The study was therefore considered valid. No precipitate was observed in the Petri plates when scoring the revertants at any dose-level. No toxicity was noted towards all the strains used, both with and without S9 mix. The test material did not induce any noteworthy increase in the number of revertants, both with and without S9 mix, in any of the five strains.
Under the conditions of this study, the test material was considered to be non-mutagenic.
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