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EC number: 204-265-5 | CAS number: 118-61-6
- 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
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
There is one in vitro genotoxicity study available. The test item did not induce an increase in mutation frequency in the Ames test, and therefore, it can be concluded that the test substance does not exert gentoxic effects.
The test was performed according to OECD TG 471 and in compliance to GLP.
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 15.-30.09.2016
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- July 21, 1997
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- Version / remarks:
- May 30, 2008
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Hess. Ministerium für Umwelt, Klimaschutz, Landwirtschaft und Verbraucherschutz, Wiesbaden, Germany
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- - histidine for Salmonella typhimurium
- tryptophan for Escherichia coli - Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Species / strain / cell type:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Metabolic activation system:
- Mammalian Microsomal Fraction S9 Mix
- Test concentrations with justification for top dose:
- 5000 μg/plate were chosen as maximal concentration.
- Pre-Experiment/Experiment I:
3; 10; 33; 100; 333; 1000; 2500; and 5000 μg/plate
- Experiment II:
-- Strains TA 1535 and TA 100: 3; 10; 33; 100; 333; 1000; 2500; and 5000 μg/plate
-- Strains TA 1537, TA 98, and WP2 uvrA : 10; 33; 100; 333; 1000; 2500; and 5000 μg/plate - Vehicle / solvent:
- DMSO
The solvent was chosen because of its solubility properties and its relative nontoxicity to the bacteria. - Untreated negative controls:
- yes
- Remarks:
- untreated
- Negative solvent / vehicle controls:
- yes
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- Remarks:
- Without metabolic activation
- Positive controls:
- yes
- Positive control substance:
- other: 4-nitro-o-phenylene-diamine, 4-NOPD
- Remarks:
- Without metabolic activation
- Positive controls:
- yes
- Positive control substance:
- methylmethanesulfonate
- Remarks:
- Without metabolic activation
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoanthracene
- Remarks:
- With metabolic activation
- Details on test system and experimental conditions:
- METHOD OF APPLICATION:
in agar (plate incorporation) in Experiment I and pre-incubation in Experiment II.
DURATION
- Exposure duration: 48h at 37°C
NUMBER OF REPLICATIONS: 3
ACCEPTANCE CRITERIA:
The Salmonella typhimurium and Escherichia coli reverse mutation assay is considered acceptable if it meets the following criteria:
- regular background growth in the negative and solvent control
- the spontaneous reversion rates in the negative and solvent control are in the range of our historical data
- the positive control substances should produce an increase above the threshold of twice (strains TA 98, TA 100, and WP2 uvrA) or thrice (strains TA 1535 and TA 1537) the colony count of the corresponding solvent control
- a minimum of five analysable dose levels should be present with at least three dose levels showing no signs of toxic effects, evident as a reduction in the number of revertants below the indication factor of 0.5. - Rationale for test conditions:
- these are according to the OECD guideline 471
- Evaluation criteria:
- - A test item is considered as a mutagen if a biologically relevant increase in the number of revertants exceeding the threshold of twice (strains TA 98, TA 100, and WP2 uvrA) or thrice (strains TA 1535 and TA 1537) the colony count of the corresponding solvent control is observed.
- A dose dependent increase is considered biologically relevant if the threshold is exceeded at more than one concentration.
- An increase exceeding the threshold at only one concentration is judged as biologically relevant if reproduced in an independent second experiment.
- A dose dependent increase in the number of revertant colonies below the threshold is regarded as an indication of a mutagenic potential if reproduced in an independent second experiment.
However, whenever the colony counts remain within the historical range of negative and solvent controls such an increase is not considered biologically relevant. - Statistics:
- According to the OECD guideline 471, a statistical analysis of the data is not mandatory.
- Key result
- 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
- Remarks:
- solvent
- Positive controls validity:
- valid
- Key result
- 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
- Remarks:
- solvent
- Positive controls validity:
- valid
- Key result
- Species / strain:
- S. typhimurium TA 98
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Remarks:
- solvent
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- 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
- Remarks:
- solvent
- 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:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Remarks:
- solvent
- Positive controls validity:
- valid
- Additional information on results:
- - The test item precipitated in the overlay agar in the test tubes from 1000 to 5000 μg/plate in the first experiment and from 2500 to 5000 μg/plate in the second experiment. In the overlay agar on the incubated agar plates no precipitation of the test item was observed.
- The plates incubated with the test item showed reduced background growth in all strains used with and without S9 mix.
- Toxic effects, evident as a reduction in the number of revertants (below the indication factor of 0.5), were observed in all strains. - Remarks on result:
- other: not mutagenic
- Conclusions:
- The test item is considered to be non-mutagenic in this Salmonella typhimurium and Escherichia coli reverse mutation assay.
- Executive summary:
This study was performed to investigate the potential of the test item to induce gene mutations according to the plate incorporation test (experiment I) and the pre-incubation test (experiment II) using the Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100, and the Escherichia coli strain WP2 uvrA. The test was performed according to OECD TG 471 and in compliance to GLP.
The assay was performed in two independent experiments both with and without liver microsomal activation. Each concentration, including the controls, was tested in triplicate. The test item was tested at the following concentrations:
Pre-Experiment/Experiment I:
3; 10; 33; 100; 333; 1000; 2500; and 5000 μg/plate
Experiment II:
Strains TA 1535 and TA 100: 3; 10; 33; 100; 333; 1000; 2500; and 5000 μg/plate
Strains TA 1537, TA 98, and WP2 uvrA : 10; 33; 100; 333; 1000; 2500; and 5000 μg/plate
The test item precipitated in the overlay agar in the test tubes from 1000 to 5000 μg/plate in the first experiment and from 2500 to 5000 μg/plate in the second experiment. In the overlay agar on the incubated agar plates no precipitation of the test item was observed.
The plates incubated with the test item showed reduced background growth in all strains used with and without S9 mix. Toxic effects, evident as a reduction in the number of revertants (below the indication factor of 0.5), were observed in all strains.
No substantial increase in revertant colony numbers of any of the five tester strains was observed following treatment with the test item at any dose level, neither in the presence nor absence of metabolic activation (S9 mix). There was also no tendency of higher mutation rates with increasing concentrations in the range below the generally acknowledged border of biological relevance. Appropriate reference mutagens were used as positive controls and showed a distinct increase of induced revertant colonies.
In conclusion, it can be stated that during the described mutagenicity test and under the experimental conditions reported, the test item did not induce gene mutations by base pair changes or frameshifts in the genome of the strains used.
Therefore, the test item is considered to be non-mutagenic in this Salmonella typhimurium and Escherichia coli reverse mutation assay.
Reference
Experiment I
Metabolic | Test | Dose Level | Revertant Colony Counts (Mean ±SD) | ||||
Activation | Group | (per plate) | |||||
TA 1535 | TA 1537 | TA 98 | TA 100 | WP2 uvrA | |||
Without Activation | DMSO | 13 ± 4 | 12 ± 4 | 31 ± 12 | 150 ± 10 | 45 ± 3 | |
Untreated | 12 ± 3 | 11 ± 3 | 27 ± 5 | 190 ± 12 | 39 ± 6 | ||
ETHYL | 3 µg | 12 ± 1 | 13 ± 4 | 28 ± 6 | 172 ± 8 | 47 ± 3 | |
SALICYLATE | 10 µg | 9 ± 3 | 8 ± 2 | 22 ± 3 | 173 ± 11 | 40 ± 3 | |
33 µg | 11 ± 4 | 9 ± 3 | 23 ± 3 | 169 ± 12 | 42 ± 8 | ||
100 µg | 14 ± 4 | 8 ± 1 | 23 ± 8 | 168 ± 5 | 35 ± 13 | ||
333 µg | 15 ± 1 | 8 ± 2 | 25 ± 3 | 121 ± 8 | 31 ± 1 | ||
1000 µg | 12 ± 3R | 10 ± 3R | 18 ± 3 | 67 ± 6R | 27 ± 6 | ||
2500 µg | 11 ± 4R | 8 ± 3R | 29 ± 4R | 63 ± 6R | 31 ± 6 | ||
5000 µg | 10 ± 1R | 4 ± 1M R | 23 ± 7R | 57 ± 4R | 37 ± 3 | ||
NaN3 | 10 µg | 1343 ± 27 | 1842 ± 401 | ||||
4-NOPD | 10 µg | 526 ± 36 | |||||
4-NOPD | 50 µg | 75 ± 13 | |||||
MMS | 2.0 µL | 791 ± 40 | |||||
With Activation | DMSO | 15 ± 5 | 10 ± 3 | 36 ± 13 | 110 ± 5 | 69 ± 9 | |
Untreated | 14 ± 3 | 12 ± 2 | 42 ± 10 | 189 ± 6 | 62 ± 16 | ||
ETHYL | 3 µg | 12 ± 3 | 12 ± 2 | 44 ± 6 | 123 ± 8 | 42 ± 4 | |
SALICYLATE | 10 µg | 13 ± 5 | 10 ± 3 | 35 ± 10 | 158 ± 24 | 60 ± 6 | |
33 µg | 9 ± 5 | 12 ± 3 | 30 ± 3 | 149 ± 19 | 53 ± 12 | ||
100 µg | 14 ± 3 | 6 ± 1 | 38 ± 8 | 164 ± 2 | 50 ± 3 | ||
333 µg | 11 ± 4 | 10 ± 1 | 34 ± 8 | 132 ± 13 | 43 ± 4 | ||
1000 µg | 7 ± 2R | 7 ± 3R | 27 ± 7R | 41 ± 8R | 48 ± 9 | ||
2500 µg | 2 ± 0M R | 2 ± 1R M | 6 ± 1M R | 7 ± 2M R | 34 ± 5R | ||
5000 µg | 2 ± 1M R | 0 ± 0R | 1 ± 1R | 0 ± 0R | 17 ± 4M R | ||
2-AA | 2.5 µg | 349 ± 10 | 361 ± 23 | 4292 ± 624 | 2005 ± 255 | ||
2-AA | 10.0 µg | 400 ± 19 |
Experiment II
Metabolic | Test | Dose Level | Revertant Colony Counts (Mean ±SD) | ||||
Activation | Group | (per plate) | |||||
TA 1535 | TA 1537 | TA 98 | TA 100 | WP2 uvrA | |||
Without Activation | DMSO | 10 ± 3 | 15 ± 3 | 32 ± 3 | 171 ± 16 | 51 ± 7 | |
Untreated | 10 ± 4 | 19 ± 2 | 31 ± 11 | 202 ± 5 | 42 ± 2 | ||
ETHYL | 3 µg | 8 ± 2 | 181 ± 11 | ||||
SALICYLATE | 10 µg | 11 ± 2 | 15 ± 6 | 23 ± 4 | 158 ± 3 | 46 ± 2 | |
33 µg | 13 ± 4 | 15 ± 1 | 28 ± 2 | 171 ± 21 | 36 ± 14 | ||
100 µg | 11 ± 1 | 14 ± 4 | 30 ± 6 | 160 ± 6 | 39 ± 7 | ||
333 µg | 14 ± 2 | 8 ± 3 | 23 ± 1 | 52 ± 3R | 23 ± 4 | ||
1000 µg | 7 ± 2R | 5 ± 1M R | 11 ± 1M R | 62 ± 7R | 15 ± 3M R | ||
2500 µg | 10 ± 5R | 5 ± 1M R | 7 ± 2M R | 48 ± 13R | 3 ± 1R M | ||
5000 µg | 11 ± 3R | 5 ± 1M R | 4 ± 1M R | 1 ± 0R | 3 ± 1M R | ||
NaN3 | 10 µg | 1333 ± 40 | 2108 ± 156 | ||||
4-NOPD | 10 µg | 548 ± 54 | |||||
4-NOPD | 50 µg | 84 ± 6 | |||||
MMS | 2.0 µL | 841 ± 127 | |||||
With Activation | DMSO | 16 ± 4 | 15 ± 4 | 34 ± 3 | 165 ± 23 | 56 ± 5 | |
Untreated | 14 ± 2 | 19 ± 7 | 46 ± 8 | 206 ± 4 | 56 ± 7 | ||
ETHYL | 3 µg | 14 ± 6 | 172 ± 6 | ||||
SALICYLATE | 10 µg | 13 ± 2 | 15 ± 1 | 37 ± 8 | 151 ± 12 | 54 ± 10 | |
33 µg | 14 ± 2 | 12 ± 3 | 30 ± 2 | 152 ± 9 | 63 ± 4 | ||
100 µg | 16 ± 4 | 10 ± 6 | 40 ± 9 | 141 ± 9 | 53 ± 5 | ||
333 µg | 11 ± 3 | 8 ± 3 | 27 ± 3 | 51 ± 5R | 58 ± 2 | ||
1000 µg | 3 ± 1M R | 1 ± 0M R | 9 ± 3M R | 23 ± 2R | 21 ± 5M R | ||
2500 µg | 0 ± 0M R | 1 ± 0M R | 0 ± 0M R | 1 ± 0R | 15 ± 4M R | ||
5000 µg | 0 ± 0M R | 0 ± 0M R | 0 ± 0M R | 0 ± 0R | 0 ± 0M R | ||
2-AA | 2.5 µg | 365 ± 11 | 193 ± 9 | 3421 ± 397 | 4468 ± 178 | ||
2-AA | 10.0 µg | 394 ± 16 |
NaN3 = sodium azide
2-AA = 2-aminoanthracene
4-NOPD = 4-nitro-o-phenylene-diamine
MMS = methyl methane sulfonate
R = Reduced background growth
M = Manual count
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
There is one in vitro study available that assessed the possible genotoxic potential of the test substance. It was performed according to GLP and internationally accepted guidelines.
Ames assay:
This study was performed to investigate the potential of the test item to induce gene mutations according to the plate incorporation test (experiment I) and the pre-incubation test (experiment II) using the Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100, and the Escherichia coli strain WP2 uvrA. The test was performed according to OECD TG 471 and in compliance to GLP. The assay was performed in two independent experiments both with and without liver microsomal activation. Each concentration, including the controls, was tested in triplicate. The test item was tested at the following concentrations:
Pre-Experiment/Experiment I:
3; 10; 33; 100; 333; 1000; 2500; and 5000 μg/plate
Experiment II:
Strains TA 1535 and TA 100: 3; 10; 33; 100; 333; 1000; 2500; and 5000 μg/plate
Strains TA 1537, TA 98, and WP2 uvrA : 10; 33; 100; 333; 1000; 2500; and 5000 μg/plate
No substantial increase in revertant colony numbers of any of the five tester strains was observed following treatment with the test item at any dose level, neither in the presence nor absence of metabolic activation (S9 mix). There was also no tendency of higher mutation rates with increasing concentrations in the range below the generally acknowledged border of biological relevance.
Appropriate reference mutagens were used as positive controls and showed a distinct increase of induced revertant colonies.
In conclusion, it can be stated that during the described mutagenicity test and under the experimental conditions reported, the test item did not induce gene mutations by base pair changes or frameshifts in the genome of the strains used. Therefore, the test item is considered to be non-mutagenic in this Salmonella typhimurium and Escherichia coli reverse mutation assay.
Justification for classification or non-classification
The key study is well documented and according to GLP and internationally accepted guidelines.
As no genotoxic effects is observed in the available study addressing genetic toxicity, classification for genetic toxicity under EU Regulation No. 1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures (CLP) is not required.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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