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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 946-322-3 | 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
Endpoint summary
Administrative data
Key value for chemical safety assessment
Genetic toxicity in vitro
Description of key information
A mutagenicity study has been conducted in in-vitro test systems where the Ames test on Salmonella typhimurium and Escherichia coli (OECD 471), turned out to be negative.
This indicates clearly a non mutagenic potential in in-vitro conditions.
It was judged that the test item is non mutagenic in vitro.
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:
- Experimental starting date: 13 February 2008 and Experimental completion date: 26 February 2008
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
- Target gene:
- The Salmonella typhimurium histidine (his) and the E. coli tryptophan (trp) reversion system measures his- his+ and trp- trp+ reversions, respectively. The S. typhimurium and Escherichia coli strains are constructed to differentiate between base pair (TA 1535, TA 100, and WP2 uvrA) and frameshift (TA 1537, TA 98) mutations.
- Species / strain / cell type:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Details on mammalian cell type (if applicable):
- Not applicable
- Additional strain / cell type characteristics:
- not applicable
- Species / strain / cell type:
- E. coli WP2 uvr A
- Details on mammalian cell type (if applicable):
- Not applicable
- Additional strain / cell type characteristics:
- not applicable
- Metabolic activation:
- with and without
- Metabolic activation system:
- Phenobarbital/-Naphthoflavone induced rat liver S9 is used as the metabolic activation system.
- Test concentrations with justification for top dose:
- - In the pre-experiment the concentration range of the test item was 3 – 5000 microg/plate. The pre-experiment is reported as experiment I.
Since no toxic effects were observed 5000 microg/plate were chosen as maximal concentration.
- The concentration range included two logarithmic decades. The following concentrations were tested in experiment II: 10; 33; 100; 333; 1000; 2500; and 5000 microg/plate - Vehicle / solvent:
- On the day of the experiment, the test item was dissolved in DMSO (MERCK, D-64293 Darmstadt; purity > 99 %).
The solvent was chosen because of its solubility properties and its relative non-toxicity to the bacteria.
The test item precipitated in the test tubes and on the agar plates from 333 - 5000 microg/plate.
The undissolved particles had no influence on the data recording. - Untreated negative controls:
- yes
- Remarks:
- Concurrent untreated and solvent controls were performed.
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- Dissolved in deionised water
- Positive control substance:
- sodium azide
- Remarks:
- Sodium azide is the positive control without metabolic activation for strains TA 1535 and TA 100. NaN3 is used at 10 microg/plate.
- Untreated negative controls:
- yes
- Remarks:
- Concurrent untreated and solvent controls were performed.
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- Dissolved in DMSO
- Positive control substance:
- other: 4-nitro-o-phenylene-diamine, (4-NOPD)
- Remarks:
- 4-NOPD is the positive control without metabolic activation for strains TA 1537 and TA 98. 4-NOPD is used at 10 microg/plate for TA 98 and at 50 microg/plate for TA 1537.
- Untreated negative controls:
- yes
- Remarks:
- Concurrent untreated and solvent controls were performed.
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- Dissolved in deionised water
- Positive control substance:
- methylmethanesulfonate
- Remarks:
- MMS is the positive control without metabolic activation for strains WP2 uvrA. MMS is used at 3 microg/plate for WP2 uvrA.
- Untreated negative controls:
- yes
- Remarks:
- Concurrent untreated and solvent controls were performed.
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- no
- Positive controls:
- yes
- Remarks:
- Dissolved in DMSO
- Positive control substance:
- other: 2-aminoanthracene, 2-AA
- Remarks:
- 2-AA is the positive control with metabolic activation for strains TA1535, TA100, TA1537, TA98 and WP2 uvrA. 2-AA is used at 2.5 microg/plate for TA1535, TA1537, TA98 and TA100 and used at 10 microg/plate for WP2 uvrA.
- Details on test system and experimental conditions:
- METHOD OF APPLICATION:
- For the experiment I: plate incorporation
- For the experiment II: pre-incubation test
Storage: The strain cultures were stored as stock cultures in ampoules with nutrient broth + 5 % DMSO (MERCK, D-64293 Darmstadt) in liquid nitrogen.
Precultures:From the thawed ampoules of the strains 0.5 mL suspension was transferred into 250 mL Erlenmeyer flasks containing 20 mL nutrient medium. A solution of 20 LL ampicillin (25 Lg/mL) was added to the strains TA 98 and TA 100. This nutrient medium contains per litre:
- 8 g Merck Nutrient Broth (MERCK, D-64293 Darmstadt)
- 5 g NaCl (MERCK, D-64293 Darmstadt)
The bacterial cultures were incubated in a shaking water bath for 4 hours at 37° C.
Selective Agar: The plates with the selective agar were obtained from E. Merck, D-64293 Darmstadt.
NUMBER OF REPLICATIONS: Each concentration, including the controls was tested in triplicate - Evaluation criteria:
- Evaluation of Results
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.
- Species / strain:
- other: S. typhimurium TA 1535, TA 98 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- Toxic effect, evident as a reduction in the number of revertant were observed in the experiment II with metabolic activation at 5000 microg/L
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- E. coli WP2 uvr A
- Metabolic activation:
- with
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Remarks:
- No toxic effect observed neither in Experiment I and II (with and without metabolic activation).
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- S. typhimurium TA 1537
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Remarks:
- Toxic effect, evident as a reduction in the number of revertant were observed in the experiment II with and without metabolic activation at 2500 and 5000 microg/L with S9 mix and at 500 microg/plate without S9 mix.
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: all strains/cell types tested
- Remarks:
- Migrated from field 'Test system'.
- Conclusions:
- 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 substance 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 in the plate incorporation test (experiment I) and the preincubation test (experiment II) using the Salmonella typhimurium strains TA 1535, TA 1537, TA 98, and TA 100, and the Escherichia coli strain WP2 uvrA.
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 microg/plate
- Experiment II: 10; 33; 100; 333; 1000; 2500; and 5000 microg/plate
The plates incubated with the test item showed normal background growth up to 5000 microg/plate with and without metabolic activation in both independent experiments.
No toxic effects, evident as a reduction in the number of revertants, occurred in the test groups with and without metabolic activation in experiment I. In experiment II, toxic effects were observed at 5000 microg/plate in strain TA 1537 without metabolic activation and in
strains TA 1535, TA 1537, TA 98, and TA 100 with metabolic activation.
No substantial increase in revertant colony numbers of any of the five tester strains was observed following treatment with the 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.
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 substance is considered to be non-mutagenic in this Salmonella typhimurium and Escherichia coli reverse mutation assay.
Reference
The test item was assessed for its potential to induce gene mutations in the plate incorporation test (experiment I) and the pre-incubation test (experiment II) using Salmonella typhimurium strains TA 1535, TA 1537, TA 98, and TA 100, and the Escherichia coli strain WP2 uvrA.
The assay was performed in two independent experiments both with and without liver microsomal activation. Each concentration and the controls were 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 microg/plate
Experiment II: 10; 33; 100; 333; 1000; 2500; and 5000 microg/plate
The plates incubated with the test item showed normal background growth up to 5000 microg/plate with and without S9 mix in both experiments.
Toxic effects, evident as a reduction in the number of revertants (below the indication factor of 0.5) were observed at the following concentrations:
Strain | Experiment I | Experiment II | ||
Without S9 mix | With S9 mix | Without S9 mix | With S9 mix | |
TA 1535 | / | / | / | 5000 |
TA 1537 | / | / | 5000 | 2500/5000 |
TA 98 | / | / | / | 5000 |
TA 100 | / | / | / | 5000 |
WP2 uvrA | / | / | / | / |
/ no toxic effects observed
No substantial increase in revertant colony numbers of any of the five tester strains was observed following treatment with the 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.
Appropriate reference mutagens were used as positive controls. They 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.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
A reliable bacterial reverse mutation test is available and was
performed according to OECD/EC guidelines.
Regarding this in vitro test, the Ames test turnes to be negative on Salmonella typhimurium and Escherichia coli
The test item was found to be be negative in the Ames test (OECD 471).
Justification for classification or non-classification
Based on the above mentioned results the substance does not need to be classified according to CLP regulation (Regulation EC No. 1272/2008) and DSD (Directive 67/548/EEC).
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.