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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 224-929-8 | CAS number: 4559-86-8
- 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
Genetic toxicity: in vivo
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Remarks:
- Type of genotoxicity: DNA damage and/or repair
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2012
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 012
- Report date:
- 2012
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- micronucleus assay
Test material
- Reference substance name:
- Tetrabutylurea
- EC Number:
- 224-929-8
- EC Name:
- Tetrabutylurea
- Cas Number:
- 4559-86-8
- Molecular formula:
- C17H36N2O
- IUPAC Name:
- 1,1,3,3-tetrabutylurea
- Test material form:
- other: liquid
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: CD / Crl: CD(SD)
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- Supplier: Charles River Laboratories, Germany
Number of animals: 70 (35 males and 35 females), i.e. 5 males and 5 females per group
Age (at start of administration): 31-33 days
Body weight: 86-122 g
Acclimatisation period: At least 5 adaptation days
Diet: Commercial ssniff® R/M-H V1534. Feeding was discontinued approx. 16 hours before administration; only tap water was then available ad libitum.
Housing: The animals were kept in groups of 2 - 3 by sex in MAKROLON cages (type III plus) at a room temperature of 22 +/- 3°C (maximum range) and a relative humidity of 55 +/- 15% (maximum range).
The rooms were lit (about 150 lux at approx. 1.50 m room height) and darkened for periods of 12 hours each.
Drinking water: ad libitum
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- 0.8% aqueous hydroxypropylmethylcellulose
- Details on exposure:
- Administration volume: 20 mL/kg b.w.
Preliminary test
The dose levels had been selected based on a preliminary oral acute toxicity study employing one animal per sex and dose. Three dose levels of 500, 1000 and 2000 mg Tetrabutylurea/kg b.w. were tested. The administration volume was 20 mL/kg b.w. No signs of systemic toxicity were noted up to the highest dose level of 2000 mg/kg b.w.
Hence, three ascending doses of 500, 1000 and 2000 mg Tetrabutylurea/kg b.w. were employed.
Main study
Three dose levels are used for the first sampling time (24 h). The dose levels should cover a range from the maximum toxicity to little or none. Only the highest dose is used at the later sampling time (48 h). The highest dose is defined as the dose producing signs of toxicity such that higher dose levels, based on the same dosing regimen, would be expected to produce lethality. The highest dose may also be defined as the dose that produces some indication of toxicity of the bone marrow (e.g. reduction of the proportion of immature erythrocytes among total erythrocytes in the bone marrow). If no toxicity occurs 2000 mg/kg b.w. is the recommended highest reasonable dose level. - Duration of treatment / exposure:
- Single dose
- Frequency of treatment:
- Single dose
- Post exposure period:
- 24 or 48 h
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 500, 1000 or 2000 mg/kg bw
Basis:
- No. of animals per sex per dose:
- 5 m / 5 f
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Negative reference item
0.8% aqueous hydroxypropylmethylcellulose
Route of administration: Oral by gavage
Administration volume: 20 mL/kg b.w.
Positive reference item
Cyclophosphamide
Dose level: 27 mg/kg b.w.
Route of administration: Intraperitoneal
Vehicle: 0.9% NaCl solution
Administration volume: 20 mL/kg b.w.
Examinations
- Tissues and cell types examined:
- bone marrow cells
- Details of tissue and slide preparation:
- Bone marrow smears were prepared from all treatment groups 24 hours post administration. Additional samples were prepared from the vehicle control and the high dose group 48 hours post administration. The femurs were excised below the knee and at the iliac joint. The bone marrow was flushed out with calf serum and centrifuged at 850 x g for 3 to 5 minutes. The supernatant was removed and the sediment resuspended in a drop of calf serum by using a Pasteur Pipette. Then a smear of 30 to 60 mm length was prepared. After air drying, the preparations were immediately fixed in methanol for 5 minutes. Cells were stained for 6 minutes using filtered Mayers Haemaleum. The slides were rinsed with cold tap water for 5 minutes and then further stained in 0.5% w/v ethanolic eosin solution for 1 minute. The slides were again left to air-dry before being dipped in xylene and mounted.
Analysis
The slides were coded and randomised before microscopic analysis. Two thousand polychromatic erythrocytes per animal were scored for the incidence of micronuclei. The ratio of polychromatic (PCE) to normochromatic erythrocytes (NCE) was determined for each animal by counting a total of thousand erythrocytes. - Evaluation criteria:
- The test chemical was considered as clearly positive in this assay if:
a statistically significant increase in the frequency of micronucleated PCE occurred for at least one dose at one kill time
the frequency of micronucleated PCE at such a point exceeded the historical control range
corroborating evidence was obtained, for example, increased but statistically insignificant frequencies or micronucleated PCE at other doses or kill times, or dose response profiles. - Statistics:
- yes
Results and discussion
Test results
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): negative
Tetrabutylurea tested up to the highest reasonable dose level of 2000 mg/kg b.w. by single oral administration showed no mutagenic properties in the rat bone marrow micronucleus test at the two tested sampling times of 24 hours and 48 hours. - Executive summary:
Tetrabutylurea was assayed in an in vivo bone marrow micronucleus test in the rat for the detection of damage to the chromosomes or the mitotic apparatus following single oral administration of the test item. The dose levels had been selected based on a preliminary oral acute toxicity study employing one animal per sex and dose. Three dose levels of 500, 1000 and 2000 mg Tetrabutylurea/kg b.w. were tested. The administration volume was 20 mL/kg b.w. No signs of systemic toxicity were noted up to the highest dose level of 2000 mg/kg b.w. For the main study three ascending doses of 500, 1000 and 2000 mg Tetrabutylurea/kg b.w., p.o. were administered. Further groups received the vehicle (0.8% aqueous hydroxypropylmethylcellulose) and one further group the positive reference item cyclophosphamide (27 mg/kg b.w., i.p.). Each group consisted of 5 male and 5 female rats. Immediately after sacrifice, bone marrow smears were prepared. Two sampling times were employed in this study: 24 hours after administration, samples were prepared from the vehicle, positive reference item and all 3 doses of test item-treated animals; 48 hours after administration, samples were prepared only from the vehicle control and high dose-treated animals. Two thousand (2000) erythrocytes were evaluated per animal.
No signs of systemic toxicity were noted up to the highest dose level of 2000 mg/kg b.w. (sacrifice after 24 or 48 hours). Tetrabutylurea did not increase the incidence of micronucleated polychromatic erythrocytes (PCE) at any of the three tested dose levels of 500, 1000 or 2000 mg/kg b.w. The incidences of PCEs combined for male and female animals were 0.7 or 0.8 micronuclei per 1000 PCEs for the samples collected 24 and 48 hours post administration. The corresponding value for vehicle control (negative reference) was 1.0 or 0.6 micronuclei per 1000 PCEs (sacrifice after 24 or 48 hours, respectively). Administration of cyclophosphamide (positive reference) significantly increased the number of micronuclei to 19.6 per 1000 PCEs.
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.