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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 406-040-9 | CAS number: 125643-61-0
- 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 vivo
Description of key information
Link to relevant study records
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From July 03rd, 1989 to November 01st, 1989
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study performed according to international guidelines and GLP.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
- Version / remarks:
- Official Journal of the European Communities No L 251 137-139
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OTS 798.5395 (In Vivo Mammalian Cytogenics Tests: Erythrocyte Micronucleus Assay)
- Version / remarks:
- Guidelines 52 FR 19080 (May 20, 1987; effective June 19, 1987), 798.5395.
- Deviations:
- no
- GLP compliance:
- yes
- Type of assay:
- micronucleus assay
- Species:
- hamster, Chinese
- Strain:
- other: Chinese hamster (Cricetulus griseus) random outbred strain
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Strain as cited inthe reported: Chinese hamster (Cricetulus griseus) random outbred strain
- Source: CIBA-GEIGY Tierfarm, Sisseln.
- Weights at test initiation:
- tolerability test: females 27-33 g, males 31-33 g
- mutagenicity test: females 23-33 g, males 26-33 g
- Days of acclimatization: at least 3 days
- Diet: standard diet NAFAG No.924, ad libitum
- Water: tap water ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23°C
- Humidity (%): 58-75%
- Air changes (per hr): air-conditioned room, no further details
- Photoperiod (hrs dark / hrs light): 12 hrs/12 hrs - Route of administration:
- oral: gavage
- Vehicle:
- Klucel 0.5%
- Duration of treatment / exposure:
- The animals were sacrificed after 16, 24 and 48 hours post treatment
- Frequency of treatment:
- Single administration by gavage
- Post exposure period:
- 16, 24 and 48 hours (8 female and 8 male animals per sampling time point were sacrificed)
- Remarks:
- Doses / Concentrations:
5000 mg/kg bw
Basis:
nominal conc. - No. of animals per sex per dose:
- 8
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- 64 mg/kg bw Cyclophosphamide in 20 mL/kg Klucel 0.5% served for positive control substance. the animals were sacrificed after 24 hours following treatment.
- Tissues and cell types examined:
- Bone marrow smears.
- Details of tissue and slide preparation:
- Following sacrifice of the animals, bone marrow was harvested from the shafts of both femurs with fetal calf serum. After centrifugation small drops of the sediment mixture were transferred on the end of a slide, spread out with the aid of a polished cover glass and the preparations were air-dried. Within 24 hours, the slides were stained with undiluted May-Grünwald solution for 3 minutes and then with May-Grünwald solution/water (1:1) for 2 minutes. After being rinsed in distilled water, the slides were left immersed in diluted Giemsa solution (16.6%), for 10 miniutes. After rinsing with distilled water and air-drying, the slides were cleared in Xylene and mounted.
The slides of five animals from each sex showing the best differentiation between mature and polychromatic erythrocytes were selected for scoring. The slides of five female and five male animals each of the negative control group and of the dosage group sacrificed at 16, 24 and 48 hours post-treatment were examined. From the animals of the positive control group which were sacrificed 24 hours after application, the slides of five female and five male animals were scored. 1000 polychromatic erythrocytes per animal each were scored for the incidence of micronuclei. To determine the mitotic activity of the red compartment, the ratio of polychromatic to normochromatic erythrocytes was calculated for each animal by counting a total of 1000 erythrocytes. A low proportion of polychromatic erythrocytes was indicative for a mitosis inhibiting activity of the test substance. - Evaluation criteria:
- A test substance is considered to be active in this test system if a statistically significant increase in the number of polychromatic erythrocytes with micronuclei in comparison with the negative control occurs at any sampling time.
- Statistics:
- Chi-squared test.
- Sex:
- male/female
- Genotoxicity:
- negative
- Remarks:
- There was no significant increase in the number of micronucleated polychromatic erythrocytes in the animals treated with 5000 mg/kg bw of the test item as compared with the negative control animals at all sampling times.
- Toxicity:
- yes
- Remarks:
- one case of mortality (male) was reported in the treatment group of 48 hours.
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- Tolerability test:
In the tolerability test the maximum dose of 5000 mg/kg bw caused no death in a group of four animals. Therefore, this dose was taken as the highest in the mutagenicity test.
Mutagenicity test:
The mutagenicity test was performed with the dosage of 5000 mg/kg bw.
One male animal died in the treatment group of 48 hours. The animals were treated once with 5000 mg/kg bw test material and bone marrow was harvested 16, 24 and 48 hours thereafter. There was no significant increase in the number of micronucleated polychromatic erythrocytes in the animals treated with the dose of 5000 mg/kg bw of test material as compared with the negative control animals at all three sampling times.
By contrast, the positive control (cyclophosphamide, 64 mg/kg bw, sampling time 24 hours) yielded a marked increase of the percentage of micronucleated cells. Here the mean percentage of polychromatic erythrocytes with micronuclei was 2.0. In comparison with the negative control (0.03 %) this value is highly significant (p <0.05). - Conclusions:
- Interpretation of results (migrated information): negative
The test item was tested in an in vivo micronucleus test (MNT) according to the OECD TG 474 (1983) using Chinese hamster. No evidence of mutagenic effects was obtained in Chinese hamsters treatedby gavage with 5000 mg/kg bw test material. - Executive summary:
The test article was tested in an in vivo micronucleus test (MNT) according to the OECD TG 474 (1983) using Chinese hamster. The test item was administered by single gavage at a dose of 5000 mg/kg bw, which had been selected based on a preliminary tolerability test. The treated animals were sacrificed 16, 24 and 48 hours thereafter. From the bone marrow smears were made and evaluation of any mutagenic effect of the test item on polychromatic erythrocytes as manifested by micronuclei was done.
At all three sampling times, no statistically significant increase in the number of micronucleated polychromatic erythrocytes in comparison with the negative control animals could be evidenced. The respective positive control with cyclophosphamide (64 mg/kg bw) yielded an average of 2.0% polychromatic erythrocytes with micronuclei. This was significantly different from the negative vehicle controls (0.03%). It is concluded that no evidence of mutagenic effects was obtained in Chinese hamsters treated with the test article in the MNT.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (negative)
Additional information
Ames test
In the presence and absence of rat liver S-9-microsomal activation system and at doses of 313-5'000 micrograms per plate, S-typhimurium strains TA 98, TA 100, TA 1535, and TA 1537 as well as E. coli strain WP2uvrA were tested for the induction of base-pair substitutions and frameshift mutations. The study was performed according to OECD testing guideline 471 and under GLP. No evidence of a mutagenic potential associated with the test substance was observed (Ciba-Geigy, 1989).
Chromosome Aberration
Chinese hamster ovary cells were treated in vitro at concentrations up to 1000 µg/ml with and without microsomal activation. The treatments lasted with microsomal activation for 3 hours and the expression periods were 15 hours and 39 hours (treatment periods not included). In the experiment without microsomal activation the combined treatment and expression periods lasted for 18 and 42 hours. The analysis of the metaphases from tests with and without microsomal activation revealed no evidence for a clastogenic effect. The procedure followed OECD Guideline 473 and the principles of GLP (Ciba-Geigy, 1993)
In vivo micronucleus test
The substance was administered orally to groups of 24 female and 24 male animals each in the negative and in the 5'000 mg/kg dose group. The positive control group consisted of 8 female and 8 male animals. Treatment occurred in a single application. 16, 24 and 48 hours after application 8 female and 8 male animals per sampling time were sacrificed and bone-marrow smears were prepared. The procedure followed OECD Guideline 474 and the principles of GLP. No evidence of a mutagenic potential associated with the test substance was observed (Ciba-Geigy, 1989).
Justification for selection of genetic toxicity endpoint
GLP-compliant in vivo study following OECD test guideline.
Justification for classification or non-classification
Dangerous Substance Directive (67/548/EEC)
The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for mutagenicity under Directive 67/548/EEC.
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 mutagenicity 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.