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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 824-772-0 | CAS number: 2060540-82-9
- 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:
- 10 February 2017 - 14 April 2017
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 017
- Report date:
- 2017
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Version / remarks:
- 21 July 1997
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- Version / remarks:
- 30 May 2008
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
Test material
Reference
- Name:
- Unnamed
- Type:
- Constituent
- Test material form:
- liquid
Method
- Target gene:
- 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):
- n/a
- Additional strain / cell type characteristics:
- not applicable
- Cytokinesis block (if used):
- n/a
- Metabolic activation:
- with and without
- Metabolic activation system:
- rat liver S9 mix
- Test concentrations with justification for top dose:
- Experiments without S9 mix
The selected dose levels were as follows:
- 4.1, 12.3, 37, 111.1, 333.3 and 1000 µg/plate for the TA 1535, TA 1537, TA 98 and TA 100 strains in the first experiment and for the TA 1537, TA 98 and TA 100 strains in the second experiment,
- 156.3, 312.5, 625, 1250, 2500 and 5000 µg/plate for the TA 102 strain in the first and second experiments,
- 20.6, 61.7, 185.2, 555.6, 1666.7 and 5000 µg/plate for the TA 1535 strain in the second experiment,
- 6.9, 20.6, 61.7, 185.2, 555.6, 1666.7 and 5000 µg/plate for the TA 1535 strain in the third experiment.
Experiments with S9 mix
The selected dose levels were as follows:
- 156.3, 312.5, 625, 1250, 2500 and 5000 µg/plate for the five strains in the first experiment and for the TA 1535, TA 1537, TA 98, and TA 102 strains in the second experiment,
- 78.13, 156.3, 312.5, 625, 1250 and 2500 µg/plate for the TA 100 strain in the second experiment,
- 3.4, 10.3, 30.9, 92.6, 277.8, 833.3 and 2500 µg/plate for the TA 1537 strain in the third experiment.
Using a test item concentration of 50 mg/mL in the vehicle and a treatment volume of 100 µL/plate, the highest recommended dose level of 5000 µg/plate was achievable. Thus, the dose levels selected for the preliminary test were 10, 100, 500, 1000, 2500 and 5000 µg/plate. - Vehicle / solvent:
- - Vehicle used: water for injections
- Justification for choice: According to available solubility data, the vehicle used for the preparation of test item dose formulations and the treatment of vehicle control plates was water for injections.
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
- benzo(a)pyrene
- mitomycin C
- other: 2-Anthramine
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation);
The preliminary test, all experiments without S9 mix and the first experiment with S9 mix were performed according to the direct plate incorporation method. The second and third experiments with S9 mix were performed according to the pre-incubation method.
DURATION
- Preincubation period: 60 minutes
- Incubation duration: 48 to 72 hours.
DETERMINATION OF CYTOTOXICITY
- Method: observation of a decrease in the number of revertant colonies and/or a thinning of the bacterial lawn.
NUMBER OF REPLICATIONS: ?????? - Rationale for test conditions:
- Not applicable.
- Evaluation criteria:
- In all cases, biological relevance (such as reproducibility and reference to historical data) was taken into consideration when evaluating the results.
The test item is considered to have shown mutagenic activity in this study if:
- 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 mean number of revertants compared with the vehicle controls is observed, in any strain, at any dose level,
- and/or a reproducible dose-response relationship is evidenced.
The test item is considered to have shown no mutagenic activity in this study if:
- neither an increase in the mean number of revertants, reaching 2-fold (for the TA 98, TA 100 and TA 102 strains) or 3-fold (for the TA 1535 and TA 1537 strains) the vehicle controls value, is observed at any of the tested dose levels,
- nor any evidence of a dose-response relationship is noted.
When inconclusive results were observed, an additional confirmatory experiment was specified by an amendment to the study plan (phrase à conserver ??????). - Statistics:
- no
Results and discussion
Test results
- 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:
- cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: no
RANGE-FINDING STUDY:
No precipitate was observed in the Petri plates when scoring the revertants at any dose levels, either with or without S9 mix.
A moderate to strong toxicity (decrease in the number of revertants and/or thinning of the bacterial lawn) was noted at dose levels = 500 µg/plate in the TA 98 and TA 100 strains without S9 mix and = 2500 µg/plate in the TA 102 strain without S9 mix as well as in the TA 98 and TA 100 strains with S9 mix.
No noteworthy toxicity was noted at any dose levels in the TA 102 strain with S9 mix.
RESULTS OF CYTOTOXICITY and GENOTOXICITY:
Experiments without S9 mix:
A moderate to strong toxicity was noted at dose levels = 111.1 µg/plate in the TA 1537 strain, = 333.3 µg/plate in the TA 100 strain, at 1000 µg/plate in the TA 98 strain, and at 5000 µg/plate in the TA 102 strain.
No noteworthy toxicity was noted in the TA 1535 strain in the first experiment whereas a toxicity was noted at 5000 µg/plate in the second experiment then at dose levels = 185.2 µg/plate in the third experiment (microcolonies was a marker of strong toxicity preventing the plates reading), though performed under the same experimental conditions.
The test item did not induce any noteworthy increase in the number of revertants, in any of the five strains, in any experiments.
These results in the absence of S9 mix met the criteria of a negative response.
Experiments with S9 mix:
Using the direct plate incorporation method (i.e. first experiment), a moderate to strong toxicity was noted at the highest tested dose level of 5000 µg/plate in the TA 1535 and TA 98 strains, and at dose levels = 2500 µg/plate in the TA 1537 and TA 100 strains. No noteworthy toxicity was noted in the TA 102 strain.
Using the pre-incubation method (i.e. second and third experiments), a moderate to strong toxicity was noted at the highest tested dose level of 5000 µg/plate in the TA 1535 and TA 102 strains, at dose levels = 2500 µg/plate in the TA 98 strain, = 833.3 µg/plate in the TA 1537 strain and = 625 µg/plate in the TA 100 strain (microcolonies was a marker of strong toxicity preventing the plates reading).
An increase in the number of revertants was noted at 2500 µg/plate in the TA 1537 strain in the second experiment (pre-incubation method). This increase exceeded the positive threshold of 3-fold the vehicle control value (6.3-fold the vehicle control value) and the corresponding mean number of revertants was above the vehicle control historical range (52.7 versus [5-18] for historical data). However, this increase occurred only at a second highly toxic dose level (strong thinning of the bacterial lawn) and was not reproduced in the third experiment performed under the same experimental conditions. Moreover, microcolonies were observed in the plates at 2500 µg/plate in the third experiment suggesting that the increase noted in the second experiment was also due to high toxicity rather than genotoxicity. As a consequence, the increase observed in the second experiment was considered to be non-biologically relevant.
The test item did not induce any other noteworthy increase in the number of revertants, in any other strains or test conditions.
The overall results in the presence of S9 mix were considered to meet the criteria of a negative response.
HISTORICAL CONTROL DATA (with ranges, means and standard deviation and confidence interval (e.g. 95%): see attached
Applicant's summary and conclusion
- Conclusions:
- Under the experimental conditions of this study, the test item did not show any mutagenic activity in the bacterial reverse mutation test with Salmonella typhimurium strains, either in the presence or absence of a rat liver metabolizing system.
- Executive summary:
The objective of this study was to evaluate the potential of the test item to induce reverse mutations in Salmonella typhimurium.
Methods
A preliminary toxicity test was performed to define the dose levels of the test item, formulated in water for injections, to be used for the mutagenicity experiments. The test item was then tested in three independent experiments, with and without a metabolic activation system, the S9 mix, prepared from a liver post-mitochondrial fraction (S9 fraction) of rats induced with Aroclor 1254.
Treatments were performed according to the direct plate incorporation method except for the second and third experiments with S9 mix, which were performed according to the pre-incubation method (60 minutes, 37°C).
Five strains of bacteria Salmonella typhimurium were used: TA 1535, TA 1537, TA 98, TA 100 and TA 102. Each strain was exposed to at least six dose levels of the test item (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.
Results
Since the test item was found to be freely soluble in the final treatment medium but toxic in the preliminary test, the selection of the highest dose level for the main experiments was based on the level of toxicity, according to the criteria specified in the international guidelines.
The mean number of revertants for the vehicle and positive controls met the acceptance criteria. Also, there were at least five analysable dose levels for each strain and test condition. The study was therefore considered to be valid.
No precipitate was observed in the Petri plates when scoring the revertants at any dose levels, either with or without S9 mix.
Experiments without S9 mix
The selected dose levels were as follows:
. 4.1, 12.3, 37, 111.1, 333.3 and 1000 µg/plate for the TA 1535, TA 1537, TA 98 and TA 100 strains in the first experiment and for the TA 1537, TA 98 and TA 100 strains in the second experiment,
. 156.3, 312.5, 625, 1250, 2500 and 5000 µg/plate for the TA 102 strain in the first and second experiments,
. 20.6, 61.7, 185.2, 555.6, 1666.7 and 5000 µg/plate for the TA 1535 strain in the second experiment,
. 6.9, 20.6, 61.7, 185.2, 555.6, 1666.7 and 5000 µg/plate for the TA 1535 strain in the third experiment.
A moderate to strong toxicity was noted at dose levels >= 111.1 µg/plate in the TA 1537 strain, >= 333.3 µg/plate in the TA 100 strain, at 1000 µg/plate in the TA 98 strain, and at 5000 µg/plate in the TA 102 strain.
No noteworthy toxicity was noted in the TA 1535 strain in the first experiment whereas a toxicity was noted at 5000 µg/plate in the second experiment then at dose levels >= 185.2 µg/plate in the third experiment (microcolonies was a marker of strong toxicity preventing the plates reading), though performed under the same experimental conditions.
The test item did not induce any noteworthy increase in the number of revertants, in any of the five strains, in any experiments.
These results in the absence of S9 mix met the criteria of a negative response.
Experiments with S9 mix
The selected dose levels were as follows:
. 156.3, 312.5, 625, 1250, 2500 and 5000 µg/plate for the five strains in the first experiment and for the TA 1535, TA 1537, TA 98, and TA 102 strains in the second experiment,
. 78.13, 156.3, 312.5, 625, 1250 and 2500 µg/plate for the TA 100 strain in the second experiment,
. 3.4, 10.3, 30.9, 92.6, 277.8, 833.3 and 2500 µg/plate for the TA 1537 strain in the third experiment.
Using the direct plate incorporation method (i.e. first experiment), a moderate to strong toxicity was noted at the highest tested dose level of 5000 µg/plate in the TA 1535 and TA 98 strains, and at dose levels >= 2500 µg/plate in the TA 1537 and TA 100 strains. No noteworthy toxicity was noted in the TA 102 strain.
Using the pre-incubation method (i.e. second and third experiments), a moderate to strong toxicity was noted at the highest tested dose level of 5000 µg/plate in the TA 1535 and TA 102 strains, at dose levels >= 2500 µg/plate in the TA 98 strain, >= 833.3 µg/plate in the TA 1537 strain and >= 625 µg/plate in the TA 100 strain (microcolonies was a marker of strong toxicity preventing the plates reading).
An increase in the number of revertants was noted at 2500 µg/plate in the TA 1537 strain in the second experiment (pre-incubation method). This increase exceeded the positive threshold of 3-fold the vehicle control value (6.3-fold the vehicle control value) and the corresponding mean number of revertants was above the vehicle control historical range (52.7 versus [5-18] for historical data). However, this increase occurred only at a second highly toxic dose level (strong thinning of the bacterial lawn) and was not reproduced in the third experiment performed under the same experimental conditions. Moreover, microcolonies were observed in the plates at 2500 µg/plate in the third experiment suggesting that the increase noted in the second experiment was also due to high toxicity rather than genotoxicity. As a consequence, the increase observed in the second experiment was considered to be non-biologically relevant.
The test item did not induce any other noteworthy increase in the number of revertants, in any other strains or test conditions.
The overall results in the presence of S9 mix were considered to meet the criteria of a negative response.
Conclusion
Under the experimental conditions of this study, the test item did not show any mutagenic activity in the bacterial reverse mutation test with Salmonella typhimurium strains, either in the presence or absence of a rat liver metabolizing system.
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.