Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 239-405-4 | CAS number: 15373-31-6
- 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
Link to relevant study records
- Endpoint:
- in vitro gene mutation study in bacteria
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2015-06-19 to 2015-06-26
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: The study was conducted according to OECD Guideline and GLP.
- 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:
- 2008
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- Salmonella typhimurium: histidine locus
Escherichia coli: tryptophan locus - Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
- Metabolic activation:
- with and without
- Metabolic activation system:
- Phenobarbital/β-naphthoflavone induced rat liver S9 mix
- Test concentrations with justification for top dose:
- 3; 10; 33; 100; 333; 1000; 2500; and 5000 μg/plate
- Vehicle / solvent:
- - Solvent used: DMSO
- Justification for choice of solvent: The solvent was chosen because of its solubility properties and its relative nontoxicity to the bacteria. - Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- sodium azide
- Remarks:
- (NaN3), 10 μg/plate, without metabolic activation TA 1535, TA 100
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 4-nitro-o-phenylene-diamine
- Remarks:
- (4-NOPD), without metabolic activation, 10 μg/plate in strain TA 98, 50 μg/plate in strain TA 1537
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- methylmethanesulfonate
- Remarks:
- (MMS), 2.0 μL/plate, without metabolic activation, WP2 uvrA
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoanthracene
- Remarks:
- (2-AA), with metabolic activation, TA 1535, TA 1537, TA 98, TA 100, WP2 uvrA
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation); preincubation
DURATION
- Preincubation period: 60 min
- Exposure duration: 48 h
NUMBER OF REPLICATIONS: 3
DETERMINATION OF CYTOTOXICITY
- Method: reduction in the number of spontaneous revertants or a clearing of the bacterial background lawn - Evaluation criteria:
- A test item was 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 was observed.
A dose dependent increase was considered biologically relevant if the threshold was exceeded at more than one concentration.
An increase exceeding the threshold at only one concentration was judged as biologically relevant if reproduced in an independent second experiment.
A dose dependent increase in the number of revertant colonies below the threshold was 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 was not considered biologically relevant. - Statistics:
- According to the OECD guideline 471, a statistical analysis of the data was not mandatory. Therefore no analysis was performed.
- Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: precipitated in the overlay agar in the test tubes from 2500 to 5000 μg/plate in the presence of S9 mix
ADDITIONAL INFORMATION ON CYTOTOXICITY:
experiment I: without S9: TA1537 (5000 μg/plate), TA100 (2500-5000 μg/plate), WP2uvrA (5000 μg/plate); with S9 mix: TA1535 and TA100 (1000-5000 μg/plate), TA1537 and TA98 and WP2uvrA (2500-5000 μg/plate)
experiment II: seen for all strains with and without S9 mix: 1000-5000 μg/plate - Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- Interpretation of results (migrated information):
negative
An in vitro reverse mutation assay study (Ames) was conducted in Salmonella typhimurium and Escherichia coli strains. It was concluded that the test substance did not induce gene mutations and was considered to be non-mutagenic. - Executive summary:
An in vitro reverse mutation assay study (Ames) was conducted according to OECD Guideline 471 in Salmonella typhimurium and Escherichia coli strains. Experiment I was performed as a plate incorporation assay. Since a negative result was obtained in this experiment, experiment II was performed as a pre-incubation assay. All tests were conducted in triplicate and concentrations between 3 μg/plate and 5000 μg/plate were tested. Strains were exposed to the test substance with and without metabolic activation with rat liver S9 mix. Cytotoxicity was observed in the plate incorporation test without S9 in three strains (TA1537 (5000 μg/plate), TA100 (2500-5000 μg/plate), WP2uvrA (5000 μg/plate)) and with S9 mix in all strains (TA1535 and TA100 (1000-5000 μg/plate), TA1537 and TA98 and WP2uvrA (2500-5000 μg/plate)). In the pre-incubation test cytotoxicity was observed in all test strains independent of metabolic activation in the range from 1000 to 5000 μg/plate. No substantial increase in revertant colony numbers of any of the five tester strains was detected following treatment with the test substance 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. Therefore it was concluded that the test substance did not induce gene mutations and it was considered to be non-mutagenic.
Reference
Plate incorporation test (experiment 1):
Dose (µg/plate) | Mean number of revertant colonies/3 replicate plates (± S.D.) with different strains of Salmonella typhimurium and E. coli | ||||
TA1535 | TA1537 | TA98 | TA100 | WP2 uvrA | |
Results without S9 | |||||
DMSO | 9 ± 1 | 9 ± 4 | 19 ± 6 | 147 ± 8 | 46 ± 8 |
Untreated | 8 ± 2 | 9 ± 4 | 25 ± 2 | 152 ± 17 | 53 ± 1 |
3 | 10 ± 3 | 9 ± 2 | 21 ± 7 | 166 ± 21 | 49 ± 9 |
10 | 9 ± 4 | 8 ± 2 | 24 ± 7 | 154 ± 7 | 42 ± 6 |
33 | 14 ± 2 | 7 ± 2 | 25 ± 4 | 151 ± 17 | 47 ± 4 |
100 | 8 ± 2 | 7 ± 1 | 26 ± 5 | 150 ± 19 | 47 ± 3 |
333 | 13 ± 4 | 5 ± 0 | 23 ± 5 | 90 ± 19 | 43 ± 6 |
1000 | 15 ± 6 | 7 ± 1 | 17 ± 5 | 67 ± 3 | 33 ± 5 |
2500 | 11 ± 3 | 7 ± 1 | 17 ± 6 | 58 ± 1 | 23 ± 2 |
5000 | 11 ± 5 | 2 ± 2 | 14 ± 2 | 63 ± 10 | 16 ± 3 |
NaN3 (10) | 1205 ± 87 | 2027 ± 45 | |||
4-NOPD (10) | 327 ± 17 | ||||
4-NOPD (50) | 72 ± 12 | ||||
MMS (2.0 µL) | 985 ± 46 | ||||
Results with S9 | |||||
DMSO | 13 ± 1 | 8 ± 0 | 27 ± 5 | 135 ± 1 | 58 ± 8 |
Untreated | 13 ± 4 | 13 ± 3 | 33 ± 2 | 149 ± 4 | 63 ± 12 |
3 | 11 ± 1 | 9 ± 4 | 30 ± 5 | 144 ± 30 | 56 ± 5 |
10 | 11 ± 3 | 11 ± 3 | 27 ± 7 | 134 ± 16 | 60 ± 9 |
33 | 15 ± 2 | 12 ± 2 | 35 ± 3 | 150 ± 20 | 56 ± 6 |
100 | 12 ± 0 | 13 ± 1 | 27 ± 6 | 150 ± 28 | 66 ± 14 |
333 | 8 ± 3 | 15 ± 2 | 35 ± 2 | 110 ± 5 | 61 ± 17 |
1000 | 6 ± 2 | 4 ± 2 | 23 ± 1 | 57 ± 13 | 29 ± 9 |
2500 | 6 ± 2 | 1 ± 1 | 4 ± 1 | 19 ± 3 | 9 ± 3 |
5000 | 1 ± 1 | 0 ± 0 | 0 ± 0 | 0 ± 1 | 1 ± 1 |
2-AA (2.5) | 446 ± 22 | 120 ± 9 | 3437 ± 519 | 3362 ± 163 | |
2-AA (10.0) | 423 ± 41 |
Pre-incubation test (experiment 2:
Dose (µg/plate) | Mean number of revertant colonies/3 replicate plates (± S.D.) with different strains of Salmonella typhimurium and E. coli | ||||
TA1535 | TA1537 | TA98 | TA100 | WP2 uvrA | |
Results without S9 | |||||
DMSO | 15 ± 1 | 10 ± 4 | 20 ± 4 | 118 ± 7 | 43 ± 6 |
Untreated | 11 ± 4 | 10 ± 2 | 21 ± 4 | 148 ± 20 | 37 ± 1 |
3 | 8 ± 3 | 8 ± 2 | 21 ± 2 | 131 ± 10 | 37 ± 4 |
10 | 7 ± 1 | 8 ± 2 | 27 ± 1 | 129 ± 9 | 35 ± 8 |
33 | 11 ± 2 | 8 ± 4 | 18 ± 2 | 124 ± 12 | 41 ± 9 |
100 | 9 ± 2 | 9 ± 2 | 24 ± 3 | 106 ± 29 | 48 ± 8 |
333 | 9 ± 4 | 7 ± 2 | 21 ± 5 | 56 ± 5 | 38 ± 6 |
1000 | 4 ± 2 | 1 ± 1 | 0 ± 1 | 26 ± 23 | 13 ± 7 |
2500 | 2 ± 2 | 0 ± 0 | 0 ± 0 | 11 ± 11 | 11 ± 8 |
5000 | 0 ± 0 | 0 ± 0 | 0 ± 0 | 5 ± 8 | 0 ± 0 |
NaN3 (10) | 1201 ± 21 | 2191 ± 176 | |||
4-NOPD (10) | 338 ± 16 | ||||
4-NOPD (50) | 92 ± 4 | ||||
MMS (2.0 µL) | 608 ± 17 | ||||
Results with S9 | |||||
DMSO | 11 ± 2 | 13 ± 1 | 37 ± 7 | 105 ± 14 | 48 ± 3 |
Untreated | 9 ± 3 | 9 ± 1 | 39 ± 9 | 146 ± 8 | 42 ± 9 |
3 | 8 ± 1 | 11 ± 2 | 32 ± 3 | 101 ± 11 | 43 ± 8 |
10 | 7 ± 2 | 12 ± 5 | 33 ± 1 | 114 ± 5 | 51 ± 5 |
33 | 10 ± 4 | 15 ± 5 | 32 ± 3 | 108 ± 10 | 57 ± 6 |
100 | 13 ± 1 | 17 ± 3 | 36 ± 2 | 108 ± 5 | 54 ± 14 |
333 | 9 ± 4 | 13 ± 3 | 33 ± 4 | 63 ± 8 | 48 ± 1 |
1000 | 0 ± 1 | 1 ± 1 | 1 ± 1 | 2 ± 3 | 21 ± 5 |
2500 | 0 ± 1 | 0 ± 0 | 0 ± 0 | 0 ± 0 | 0 ± 1 |
5000 | 0 ± 0 | 0 ± 0 | 0 ± 0 | 0 ± 0 | 0 ± 0 |
2-AA (2.5) | 420 ± 26 | 134 ± 18 | 4232 ± 148 | 3123 ± 114 | |
2-AA (10.0) | 410 ± 17 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
Genetic toxicity in vitro:
Ames test:
An in vitro reverse mutation assay study (Ames) was conducted according to OECD Guideline 471 in Salmonella typhimurium and Escherichia coli strains. Experiment I was performed as a plate incorporation assay. Since a negative result was obtained in this experiment, experiment II was performed as a pre-incubation assay. All tests were conducted in triplicate and concentrations between 3 μg/plate and 5000 μg/plate were tested. Strains were exposed to the test substance with and without metabolic activation with rat liver S9 mix. Cytotoxicity was observed in the plate incorporation test without S9 in three strains (TA1537 (5000 μg/plate), TA100 (2500-5000 μg/plate), WP2uvrA (5000 μg/plate)) and with S9 mix in all strains (TA1535 and TA100 (1000-5000 μg/plate), TA1537 and TA98 and WP2uvrA (2500-5000 μg/plate)). In the pre-incubation test cytotoxicity was observed in all test strains independent of metabolic activation in the range from 1000 to 5000 μg/plate. No substantial increase in revertant colony numbers of any of the five tester strains was detected following treatment with the test substance 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. Therefore it was concluded that the test substance did not induce gene mutations and it was considered to be non-mutagenic.
Micronucleus test:
The test item, dissolved in DMSO, was assessed for its potential to induce micronuclei in Chinese hamster V79 cells in vitro in the absence and the presence of metabolic activation by S9 mix. Two independent experiments were performed: Experiment I: Exposure 4 h (with and without metabolic activation), Experiment II: Exposure 20 h (without metabolic activation), 4 h (with metabolic activation). In each experimental group two parallel cultures were set up. Per culture 1000 cells were scored for micronuclei. The following test item concentrations were applied:
Exp. I, with and without S9 mix: 12.2, 24.4, 48.8, 97.5, 195.0, 390.0, 780.0, 1560.0 ug/mL
Exp. II, with and without S9 mix: 6.1, 12.2, 24.4, 48.8, 97.5, 195.0, 390.0, 780.0 ug/mL
In Experiments I and II, clear cytotoxicity was observed in the absence of S9 mix at the highest scored concentrations. However, in the presence of S9 mix, no clear cytotoxicity was observed up to the highest scorable concentration in Experiment I, or up to the highest applied concentration in Experiment II. In this study, no clastogenicity was observed up to the highest scored concentrations. In Experiment I, in the absence of S9 mix, and in Experiment II, in the presence of S9 mix, statistically significant increases of micronucleated cells were observed at all scored concentrations. However, in both experimental parts, there was no dose-dependency and all values were clearly within the range of the laboratory's historical control data (0.0 - 2.5 % micronucleated cells). Therefore, these observations have to be regarded as biologically irrelevant.Colcemid, mitomycin C and cyclophosphamide were used as positive controls. In conclusion, it can be stated that under the experimental conditions reported, the test item did not induce micronuclei in V79 cells.
Justification for selection of genetic toxicity endpoint
The study was conducted according to GLP and OECD and the result was similar to other in vitro tests.
Justification for classification or non-classification
The available data did not indicate genetic toxicity of the test substance in vitro. Therefore the substance is not to be classified for genetic toxicity under Regulation (EC) No 1272/2008 (CLP).
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.