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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 241-734-3 | CAS number: 17741-63-8
- 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
Bacteria:
OECD 471; GLP; S.typhimurium TA 1535, TA 1537, TA 98, TA 100 and E.coli WP2 uvrA; 33 -5000 µg/plate; no cytotoxicity; non-mutagenic
Cytogenicity:
OECD 473; GLP; human lymphocytes; 40 -150 µg/ml; no cytotoxicity; not clastogenic
Gene mutation:
OECD 476; GLP; mouse lymphoma; 62.5 -2000 µg/ml; no cytotoxicity; non-mutagenic
Link to relevant study records
- Endpoint:
- in vitro cytogenicity / chromosome aberration study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2014
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- in vitro mammalian chromosome aberration test
- Specific details on test material used for the study:
- - 98.3%
- Species / strain / cell type:
- lymphocytes: human lymphocyte cultures prepared from the pooled blood of three male donors in two independent experiments
- Details on mammalian cell type (if applicable):
- Blood from three healthy, non-smoking male volunteers from a panel of donors was used for each experiment. No donor was suspected of any virus infection or exposed to high levels of radiation or hazardous chemicals. All donors are non-smokers and are not heavy drinkers of alcohol. Donors were not taking any form of medication. HEPES-buffered RPMI medium
- Metabolic activation:
- with and without
- Metabolic activation system:
- Aroclor induced rat liver S9 mix
- Test concentrations with justification for top dose:
- Experiment 1:
+ S9 mix: 0, 40, 60, 80 ug/ml
- S9 mix: 0, 80, 100, 150 ug/ml
Experiment 2:
+ S9 mix: 0, 40, 50, 55 ug/ml
- S9 mix: 0, 45, 60, 75, 90 ug/ml - Vehicle / solvent:
- DMF
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- mitomycin C
- Remarks:
- without S9 mix
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- cyclophosphamide
- Remarks:
- with S9 mix
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Exposure duration: 3h +/- S9 mix experiment I, 20h without S9 mix and 3h with S9 mix experiment II
- Expression time (cells in growth medium): after 3h exposure 17h, after 20h exposure 0h
- Fixation time (start of exposure up to fixation or harvest of cells): after 4h exposure 18-28h, 18h and 28h exposure and fixation direct thereafter
SPINDLE INHIBITOR (cytogenetic assays): colchicine
STAIN (for cytogenetic assays): Giemsa
NUMBER OF REPLICATIONS: 2 independent experiments, samples / cultures in triplicate
NUMBER OF CELLS EVALUATED: 100 well-spread metaphases will be scored per culture
DETERMINATION OF CYTOTOXICITY
- Method: slides will be evaluated for mitotic index and cell numbers, 1000 cells per culture will be scored and values will be expressed as a percentage of the solvent controls - Evaluation criteria:
- For valid data, the test article was considered to induce clastogenic events if:
1. A proportion of cells with structural aberrations at one or more concentrations that exceeded the normal range was observed in both replicate cultures
2. A statistically significant increase in the proportion of cells with structural aberrations (excluding gaps) was observed (p0.05)
3. There was a concentration-related trend in the proportion of cells with structural aberrations (excluding gaps).
The test article was considered positive in this assay if all of the above criteria were met. - Statistics:
- The statistical method used was Fisher's exact test. The proportions of aberrant cells in each replicate were also used to establish acceptable heterogeneity between replicates by means of a binomial dispersion test.
- Species / strain:
- lymphocytes: Human Lymphocyte
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- Precipitation was observed at 55 and 150 ug/ml
- Conclusions:
- It is concluded that the test substance did not induce chromosome aberrations in cultured human peripheral blood lymphocytes following treatment in the absence and presence of rat liver metabolic activation system (S-9). Concentrations were tested up to the limit of solubility within the test system. Therefore, the test substance was considered to be non-clastogenic in this in vitro test system.
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2014
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- mammalian cell gene mutation assay
- Specific details on test material used for the study:
- - Purity: 98.3%
- Target gene:
- HPRT locus
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Details on mammalian cell type (if applicable):
- - Type and identity of media: RPMI 1640 media supplied containing L-glutamine and HEPES
- Properly maintained: yes
- Periodically checked for Mycoplasma contamination: yes
- Periodically checked for karyotype stability: yes - Metabolic activation:
- with and without
- Metabolic activation system:
- Acroclor induced liver S9 mix
- Test concentrations with justification for top dose:
- Experiment 1 ten concentrations, ranging from 50 to 1000 µg/mL in the absence of S-9 and from 25 to 625 µg/mL in the presence of S 9 mix
Experiment 2 ten concentrations, ranging from 50 to 750 µg/mL in the absence of S 9 and from 25 to 500 µg/mL in the presence of S-9 mix - Vehicle / solvent:
- DMF
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- 4-nitroquinoline-N-oxide
- Remarks:
- without S9 mix
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- benzo(a)pyrene
- Remarks:
- with S9 mix
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in medium
DURATION
- Exposure duration: 3h
- Expression time (cells in growth medium): 7 days at 37°C
- Selection time (if incubation with a selection agent): 6-7 days in TG-medium
- Fixation: At the end of the selection period, the medium will be removed and the remaining colanies will be fixed with methanol, stained with Giemsa and counted
SELECTION AGENT (mutation assays): TG-medium
NUMBER OF REPLICATIONS: two independent experiments, every sample in triplicate
NUMBER OF CELLS EVALUATED: all colonies are counted
DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency
OTHER EXAMINATIONS:
- pH
- osmolarity
- solubility
- cell morphology - Evaluation criteria:
- For valid data, the test article was considered to induce forward mutation at the hprt locus in mouse lymphoma L5178Y cells if:
1. The mutant frequency at one or more concentrations was significantly greater than that of the vehicle control (p0.05)
2. There was a significant concentration relationship as indicated by the linear trend analysis (p0.05)
3. The effects described above were reproducible.
The test article was considered positive in this assay if all of the above criteria were met. - Statistics:
- Statistical significance of mutant frequencies was carried out according to the UKEMS guidelines (Robinson et al., 1990). The control log mutant frequency (LMF) was compared with the LMF from each treatment concentration and the data were checked for a linear trend in mutant frequency with test article treatment. These tests require the calculation of the heterogeneity factor to obtain a modified estimate of variance.
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity, but tested up to precipitating concentrations
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- No marked changes in osmolality or pH. Precipitation was observed at the highest concentrations.
- Conclusions:
- It is concluded that the test substance did not induce mutation at the hprt locus of L5178Y mouse lymphoma cells when tested up to precipitating concentrations in two independent experiments in the absence and presence of a rat liver metabolic activation system (S-9). Therefore, the test substance is considered to be non-mutagenic in this in vitro test system.
- Endpoint:
- in vitro gene mutation study in bacteria
- Type of information:
- experimental study
- Adequacy of study:
- key study
- 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:
- yes
- Remarks:
- The protein concentration in the S9 preparation was 47.3 mg/mL and not in the range of 20 - 45 mg/mL as stated in the protocol.
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
- Qualifier:
- according to guideline
- Guideline:
- JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- bacterial reverse mutation assay
- Specific details on test material used for the study:
- - Purity: 99%
- Target gene:
- his-locus
- 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:
- Phenobarbital/ß-Naphthoflavone induced rat liver S9 mix
- Test concentrations with justification for top dose:
- 0; 33; 100; 333; 1000; 2500 and 5000µg/plate
- Vehicle / solvent:
- - Vehicle(s)/solvent(s) used: acetone
- Justification for choice of solvent/vehicle: the solvent was chosen because of its solubility properties and its relative non-toxicity 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:
- strains TA 1535 and TA 100, without S9 mix
- 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:
- strains TA 1537 and TA 98, without S9 mix
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- methylmethanesulfonate
- Remarks:
- strain WP2 uvrA, without S9 mix
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: 2-aminoanthracene
- Remarks:
- all strains, with S9 mix
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation) (Experiment I); preincubation (Experiment II)
DURATION
- Preincubation period: 60 minutes at 37 °C
- Exposure duration: 48 hours at 37 °C
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 article is considered positive if either a dose related and reproducible increase in the number of revertants or a biologically relevant and reproducible increase for at least one test concentration is induced.
- A test article producing neither a reproducible and dose related increase in the number of revertants, nor a biologically relevant and reproducibly positive response at any one of the test points is considered non-mutagenic in this system.
- A test article is considered mutagenic if in the strains TA 98, TA 100, and WP2 uvrA the number of reversions will be at least twice as high and in the strains TA 1535 and TA 1537 at least three times higher as compared to the spontaneous reversion rate.
- Also, a dose-dependent and reproducible increase in the number of revertants is regarded as an indication of possibly existing mutagenic potential of the test article regardless whether the highest dose induced the above described enhancement factors or not. - Statistics:
- No statistical evaluation of the data is required.
- Species / strain:
- S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Species / strain:
- E. coli WP2 uvr A
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Vehicle controls validity:
- valid
- Untreated negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- ADDITIONAL INFORMATION ON CYTOTOXICITY:
The background growth was reduced at 2500 and 5000 µg/plate with and without metabolic activation in both independent experiments.
No relevant toxic effects, evident as a reduction in the number of revertants, occurred in the test groups with and without metabolic activation. - Conclusions:
- In conclusion, it can be stated that during the described mutagenicity test and under the experimental conditions reported, the test article did not induce gene mutations by base pair changes or frameshifts in the genome of the strains used. Therefore, the test substance is considered to be non-mutagenic in this Salmonella typhimurium and Escherichia Coli reverse mutation assay.
Referenceopen allclose all
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
In a GLP-compliant study, performed according to OECD guideline 471, the test substance was assessed for its potential to induce gene mutations according to the plate incorporation test (experiment I) and the preincubation test (experiment II) at concentrations up to 5000 ug/plate using Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100, and the Escherichia coli strain WP2 uvrA.
No relevant toxic effects, evident as a reduction in the number of revertants, occurred in the test groups with and without metabolic activation. No substantial increase in revertant colony numbers of any of the five tester strains was observed following treatment with the test substance at any dose level, neither in the presence nor absence of metabolic activation (S9 mix). Therefore, the test substance is considered to be non-mutagenic in this Salmonella typhimurium and Escherichia coli reverse mutation assay.
The test item was tested in an in vitro cytogenetics assay using duplicate human lymphocyte cultures. Treatments covering a broad range of concentrations, separated by narrow intervals, were performed both in the absence and presence of metabolic activation (S-9) from Aroclor 1254-induced rats. Treatment of cells with in the absence and presence of S-9 in Experiments 1 and 2 resulted in frequencies of cells with structural chromosome aberrations that were similar to those observed in concurrent vehicle control cultures for all concentrations analysed. Numbers of aberrant cells (excluding gaps) in all treated cultures fell within the normal ranges. Therefore,the test material was considered to be non-clastogenicin this in vitro test system.
The test substance was assayed for the ability to induce mutation at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus (6-thioguanine [6TG] resistance) in mouse lymphoma cells using a fluctuation protocol. The study consisted of a cytotoxicity Range-Finder Experiment followed by two independent experiments, each conducted in the absence and presence of metabolic activation by an Aroclor 1254-induced rat liver post-mitochondrial fraction (S‑9). In Experiments 1 and 2 when tested up to precipitating concentrations, no statistically significant increases in mutant frequency, compared to the concurrent vehicle controls, were observed following treatment at any concentration analysed in the absence and presence of S‑9 and there were no statistically significant linear trends. Therefore,the test item is considered to be non-mutagenicin this in vitro test system.
Short description of key information:
The test substance was unable to induce mutation in five strains of
Salmonella typhimurium when tested up to 5000 µg/plate in the absence
and presence of a rat liver metabolic activation system.
Endpoint Conclusion: No adverse effect observed (negative)
Justification for classification or non-classification
Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for genetic toxicity under Regulation (EC) No. 1272/2008.
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.