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EC number: 202-908-4 | CAS number: 101-02-0
- 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
AMES: negative (with and without metabolic activation), no cytotoxicity; similar to OECD TG 471, GLP, K2
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:
- 1980
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 471 (Bacterial Reverse Mutation Assay)
- GLP compliance:
- yes
- Type of assay:
- bacterial reverse mutation assay
- Species / strain / cell type:
- other: S. typhimurium TA 1535, TA 1537, TA 1538, TA 98, TA 100
- Metabolic activation:
- with and without
- Metabolic activation system:
- Aroclor 1254 induced S-9 fraction from rat liver
- Test concentrations with justification for top dose:
- 5, 10, 50, 100 and 500 µg/plate
- Vehicle / solvent:
- ethanol
- Untreated negative controls:
- no
- Negative solvent / vehicle controls:
- yes
- True negative controls:
- no
- Positive controls:
- yes
- Positive control substance:
- other: see below
- Details on test system and experimental conditions:
- METHOD OF APPLICATION: in agar (plate incorporation)
DURATION
- Exposure duration: 48h at 37°C
NUMBER OF REPLICATIONS:
Samples are run in duplicate
POSITIVE CONTROLS
- with metabolic activation:
TA-1535, cyclophosphamide (200 µg/plate); TA-1537, TA-1538, TA-98 and TA-100, benzofalpyrene 5 µg/plate
- without metabolic activation:
TA-1535 and TA-100, sodium azide (1 µg/plate); TA-1537, aaminoacridine (100 µg/plate); TA-1538 and TA-98, 2-nitrofuorene (50 µg/plate) - Evaluation criteria:
- The assay is scored as the ratio of the number of macroscopic colonies on the test plate over the number of macroscopic colonies on the control plate. This is taken as the mutagenic index. A compound is considered to have a positive response if the mutagenic index is 2.0 and the apparent mutagenicity exhibits a dose response relationship.
- Species / strain:
- other: S. typhimurium TA 1535, TA 1537, TA 1538, TA 98, TA 100
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- no cytotoxicity
- Additional information on results:
- - All strains/cell types tested
TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: A white precipitate formed in the aqueous agar solution at 50, 100 and 500 µg/plate - Conclusions:
- The test article was not mutagenic under the conditions of this study described.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Genetic toxicity in vivo
Description of key information
MNT: negative in mammalian erythrocytes; mouse, according to OECD TG 474, GLP, K2
Link to relevant study records
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1981
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Principles of method if other than guideline:
- Method based on HRC Report Number TCO 17 & 18/ 81305
- GLP compliance:
- yes
- Type of assay:
- micronucleus assay
- Species:
- mouse
- Strain:
- other: COBS CD-I (ICR) BR
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River U.K. Limited, Margate, Kent
- Weight at study initiation: 18 and 21 grams
- Fasting period before study: overnight
- Housing: plastic disposable cage
- Diet: free access to Spratt's Laboratory Diet No. 1
- Water: tap water, ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Air changes (per hr): 30
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle(s)/solvent(s) used: corn oil
- Frequency of treatment:
- The total dosoges were given as two equal administrations separated by an interval of 24 hours.
- Post exposure period:
- 6h
- Dose / conc.:
- 1 250 mg/kg bw/day (actual dose received)
- Remarks:
- total dose divided over two treatments
- Dose / conc.:
- 2 500 mg/kg bw/day (actual dose received)
- Remarks:
- total dose divided over two treatments
- Dose / conc.:
- 5 000 mg/kg bw/day (actual dose received)
- Remarks:
- total dose divided over two treatments
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Mitomycin C, batch number 40F-0404, was used as the positive control compound. It was prepared as a solution in sterile 0.9% saoline at a concentration of 0.4 mg/ml. It was adminitered by IP injection.
- Tissues and cell types examined:
- The femurs were cleared of tissue and one epiphysis removed from each bone. A direct bone marrow smear was made onto a slide containing a drop of calf serum. The slide was cleaned by inversion in methanol for 24 hours and air-dried immediately before use. One smear was mode from each femur.
- Details of tissue and slide preparation:
- The prepared smears were air-dried and fixed in methanol overnight. After fixation, the smears were air-dried and placed in buffered distilled water (pH 6.8) for 10 minutes prior to staining In Giemsa (dilution Factor I part Giemsa : 9 parts buffered distilled water pH 6.8) for 10 minutes. After rinsing in buffered distilled water (pH 6.8), the slides were air-dried and mounted in OPX. The stained smears were examined by light microscopy to determine the incidence of micronucleated cells per 1000 polychromatic erythrocytes per animal and the ratio of normochromatic to polychromatic erythrocytes.
- Evaluation criteria:
- A compound was considered to show evidence of mutagenic activity if it produced a statistically significant increase in micronucleated cells compared to the concurrent negative control values.
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- yes
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF RANGE-FINDING STUDY
- Dose range: Phase I: 500, 5000, 10000, 15000, 24400 mg/kg; Phase II: 6000, 7000 and 8000 mg/kg
After administration of test substance at a total dosage of 500 mg/kg bodyweight, no toxic reactions were observed. At total dosages between 5000 and 24400 mg/ltg bodyweight, a toxic reaction consisting of tremors was observed 30 minutes after dosing. The tremors decreased over the next 1.5 hours until they were not observed two hours after each dose. From 10000 mg/kg and higher all animals died. At 6000, 7000 and 8000 mg/kg, 6/10, 6/10 and 9/10 animals died. From the above results, a top dosage of 5000 mg/kg bodyweight was chosen for the micronucleus test which, it was indicated, would cause one or two deaths.
RESULTS OF DEFINITIVE STUDY
In this experiment the negative control group gave a mean count of 0.1 micronucleated cells which was within the range for previous unrelated experiments. After administration of test substance at all dosages, the group mean micronucleated cell counts were comparable with the concurrent control value and within the laboratory standard range for negative controls obtained In previous unrelated experiments.
In this experiment the negative control group gave a mean ratio of 1.86 normochromatic to polychromatic cells. After administration of test substance at the highest total dosage of 5000 mg/kg bodyweight, the normochromatic to polychromatic cell ratios were comparable with the concurrent control values. The ratios of the two lower dosages were, therefore, not scored. The positive control group administered intraperitoneally with Mitomycin C gave a group mean ratio of 7.32 normochromatic to polychromatic cells.
At total dosages of 1250 and 2500 mg/kg bodyweight no toxic reactions or mortalities were observed. At a total dosage of 5000 mg/kg bodyweight, a toxic reaction consisting of tremors was observed 30 minutes after dosing. The tremors decreased over the next 1.5 hours until they were not observed two hours after each dose. There were 5 mortalities at this dose level. Advanced visceral autolysis prevented any post mortem examination in all animals. After administration of Mitomycin C, no toxic reactions or mortalities were observed. - Conclusions:
- Under the conditions of this study, no evidence of induced chromosomal damage or other damage leading to micronucleus formation was given in polychromatic erythrocytes of treated mice after oral administration of the test substance.
Reference
Summary of results
Number of micronucleated cells per 1000 polychromatic erythrocytes per animal | NCE/PCE Ratio | |||
Test group | mean | range | mean | range |
negative control | 0.1 | 0-1 | 1.86 | 1.01-4.96 |
1250 mg/kg test substance | 0.2 | 0-1 | + | + |
2500 mg/kg test substance | 0.2 | 0-1 | + | + |
5000 mg/kg test substance | 0.2 | 0-1 | 1.38 | 1.09-1.86 |
positive control (8 mg/kg) | 27.7 | 7-67 | 7.52 | 3.24-16.37 |
+ Slides not scores for ratio
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
AMES
In this GLP compliant in vitro bacterial gene mutation test that was conducted similar to the OECD TG 471 (K2) S. typhimurium TA 1535, TA 1537, TA 1538, TA 98, TA 100 were exposed to the test substance for 48h at concentrations of 5, 10, 50, 100 and 500 µg/plate with and without metabolic activation. Under the conditions of this study the test substance did not induce cytotoxicity and was not mutagenic (MRI, 1980).
MNT
In this GLP compliant in vivo cytogenicity test that was performed according to the OECD TG 474 (K2) five COBS CD-I (ICR) BR mice/sex/dose were dosed with the test substance at 1250, 2500 or 5000 mg/kg bw/day by gavage. The total dose was divided over two treatments. Six hours after the last dosing a micronucleus assay was performed. Under the conditions of this study, no evidence of induced chromosomal damage or other damage leading to micronucleus formation in polychromatic erythrocytes was seen in mice orally treated with the test substance (Huntingdon, 1981).
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. No indication of genotoxicity was observed in the Ames test (OECD 471, GLP) and the in vivo MNT test (OECD 474, GLP). As a result, the substance is not considered to be classified for mutagenicity under Regulation (EC) No. 1272/2008, as amended for the fourteenth time in Regulation (EC) No. 2020/217.
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