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EC number: 258-981-8 | CAS number: 54112-23-1
- 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
Acute Toxicity: inhalation
Administrative data
- Endpoint:
- acute toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- from August 28 to December 12, 2012
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- 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 403 (Acute Inhalation Toxicity)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.2 (Acute Toxicity (Inhalation))
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- standard acute method
- Limit test:
- yes
Test material
- Reference substance name:
- GRILBOND IL-6
- IUPAC Name:
- GRILBOND IL-6
- Reference substance name:
- N,N'-(methylenedi-p-phenylene)bis[hexahydro-2-oxo-1H-azepine-1-carboxamide]
- EC Number:
- 258-981-8
- EC Name:
- N,N'-(methylenedi-p-phenylene)bis[hexahydro-2-oxo-1H-azepine-1-carboxamide]
- Cas Number:
- 54112-23-1
- Molecular formula:
- C27H32N4O4
- IUPAC Name:
- 2-oxo-N-[4-({4-[(2-oxoazepane-1-carbonyl)amino]phenyl}methyl)phenyl]azepane-1-carboxamide
- Test material form:
- solid: particulate/powder
- Remarks:
- migrated information: powder
- Details on test material:
- Designation Grilbond IL-6 100%
Chemical name N,N’-(methylenedi-p-phenylene)bis[hexahydro-oxo-1H-azepine-1-carboxamide]
CAS no. 54112-23-1
EC no. 258-981-8
Molecular formula C27H32N4O4
Batch no. 9114761/024
Receipt no. 51302
Date of receipt August 03, 2012
Characteristics White powder
Water solubility Insoluble (25°C)
Storage conditions At room temperature
Manufacturer EMS-GRITECH CH-7013 Domat/Ems
Production date July 12, 2012
Stability (expiry date) July 11, 2013
Purity 99.0%
Particle size Particle size parameter provided by EMS-GRILTECH:
D10 = 4 µm
D50 = 20 µm
D95 = 45 µm
Constituent 1
Constituent 2
Test animals
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Animals
Species / Strain / Stock: Rat (Rattus norvegicus) / CD / Crl:CD(SD)
Breeder: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7 97633 Sulzfeld Germany
Age: (at start of exposure): Males: approx. 8 weeks Females: approx. 9 weeks
Body weight shortly before start of the exposure: Males: 262 - 267 g; Females: 222 - 231 g
Selection of species: The rat is a commonly used rodent species for such studies.
Identification of animals: By coloured tail marks and cage label
Number of animals: 10 (5 males and 5 females)
Groups: 1 concentration - Limit test
Concentrations: nominal: 6.67 mg/L air (mean achieved: 5.07 mg/L air, SD = 0.03 mg/L air)
Duration of experiment: at least 5 adaptation days 1 test day, 2 recovery weeks
Housing
Granulated textured wood (Granulat A2, J. Brandenburg, 49424 Goldenstedt, Germany) was used as bedding material for the cages. The cages were changed and cleaned twice a week.
Periodic analysis of the bedding material for contaminants based on EPA/USA is conducted at least once a year by LUFA-ITL (see Appendix 2: Limitation for contaminants in the bedding material).
During the 14-day observation period the animals were kept by sex in groups of 2 - 3 animals in MAKROLON cages (type III plus) at a room temperature of 21.8 °C - 25.0 °C and a relative humidity of 48% ±68%. The ranges are given with 22 °C ±3 °C (maximum range) and a relative humidity of 55% ±15% (maximum range). Deviations from the maximum range caused for example during cleaning procedures are dealt with in SOPs.
The rooms were lit (150 lux at approx. 1.50 m room height) and darkened for periods of 12 hours each.
Drinking water in bottles was offered ad libitum. Feeding was discontinued approx. 16 hours before administration; only tap water was then available ad libitum.
Administration / exposure
- Route of administration:
- inhalation: dust
- Type of inhalation exposure:
- nose only
- Vehicle:
- air
- Details on inhalation exposure:
- Route of administration: By inhalation (nose-only exposure)
Duration of exposure to the test item: 4 hours/animal
Exposure concentration: 5.07 mg/L air (mean actual concentration)
Exposure system
The study was carried out using a dynamic inhalation chamber (air changes/h (≥ 12 times)) with a nose-only exposure of the animals according to KIMMERLE & TEPPER. The apparatus consists of a cylindrical exposure chamber (volume 40 L) which holds the animals in pyrex tubes at the edge of the chamber in a radial position.
The dust of the test material was generated with a rotating brush dust generator.
The generator was fed with compressed air (5.0 bar) from a compressor (air was taken from the surrounding atmosphere of the laboratory room and filtered using an in-line disposable gas-filter).
At the bottom of the exposure chamber, the air was sucked off at a lower rate than created by the dust generator in order to produce a homogenous distribution and a positive pressure in the exposure chamber (inflow 900 L/h, outflow 800 L/h).
A manometer and an air-flow meter were used to control the constant supply of compressed air and the exhaust, respectively. Flow rates were checked hourly and corrected if necessary.
The oxygen content in the inhalation chamber was 21% v/v. It was determined at the beginning and at the end of the exposure with a DRÄGER Oxygen-analysis test set (DRÄGER Tube Oxygen 67 28 081).
The whole exposure system was mounted in an inhalation facility to protect the laboratory staff from possible hazards.
The exhaust air was sucked through gas wash-bottles. Exposure started by locating the rats into the exposure chamber after equilibration of the chamber concentration for 15 minutes.
Analysis of the dust concentration
The actual dust concentration in the inhalation chamber was measured 4 times gravimetrically with an air sample filter (Minisart SM 17598; 0.45 µm) and pump controlled by a rotameter. Dust samples were taken once every hour during the exposure. For that purpose, a probe was placed close to the animals' noses in the inhalation chamber and air was sucked through the air sample filter at a constant flow of air of 5 L/min for 1 minute. The filters were weighed before and after sampling on an analytical balance (accuracy 0.1 mg).
Temperature and humidity: The temperature (22 °C ±3 °C) and humidity was checked and noted once every hour during the exposure period of the experiment. - Analytical verification of test atmosphere concentrations:
- yes
- Duration of exposure:
- ca. 4 h
- Concentrations:
- a single dose of 5.07 mg/L air
- No. of animals per sex per dose:
- 5 males and 5 females
- Control animals:
- no
- Details on study design:
- After completion of exposure, the animals were observed for a period of 14 days. During and following exposure, observations were made and recorded systematically; individual records were maintained for each animal. A careful clinical examination was made at least once daily until all symptoms subsided, thereafter each working day. Observations on mortality were made at least once daily to minimize loss of animals to the study.
Cageside observations included but were not limited to: changes in the skin and fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, as well as somatomotor activity and behaviour pattern.
Particular attention was directed to observation of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Individual body weights of animals were determined before the exposure on test day 1 and on test days 8 and 15. Changes in weight were calculated and recorded when survival exceeds one day. At the end of the test, all animals were weighed and sacrificed.
Pathology
Necropsy of all animals was carried out and all gross pathological changes were recorded.
No microscopic examination was carried out as no pathological findings were noted at necropsy.
Due to lack of prematurely deceased animals no LC50 could be calculated.
Results and discussion
Effect levels
- Sex:
- male/female
- Dose descriptor:
- LC50
- Effect level:
- > 5 mg/L air (analytical)
- Based on:
- test mat.
- Exp. duration:
- 4 h
- Remarks on result:
- other: None of the animals died prematurely after exposure of test article. All animals gained the expected body weight.
- Mortality:
- None of the animals died prematurely.
- Clinical signs:
- other: Slight ataxia, slight tremor, slightly reduced muscle tone and slight dyspnoea immediately until 30 minutes or 3 hours after end of exposure in all 5 of 5 male and 5 of 5 female animals. No clinical observations were observed during the further 14-day obs
- Body weight:
- All animals gained the expected body weight. No treatment-related body weight effects were seen neither for males nor females over the 14-day period as all animals gained the expected body weight.
- Gross pathology:
- No pathological findings were noted at necropsy.
- Other findings:
- no data
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Based on the available data in this study, LC50(rat, 4 hours) of test article was greater than 5 mg/L air.
- Executive summary:
This acute study was performed to assess the acute inhalation toxicity of test item administered to rats for a single 4-hour period at a mean actual concentration of 5.07 mg/L air using a dynamic nose-only exposure chamber. The particle size distribution was determined with a cascade impactor. Under the present test conditions, a 4-hour exposure to Grilbond IL-6 100% at the concentration of 5.07 mg/L air revealed slight ataxia, slight tremor, slightly reduced muscle tone and slight dyspnoea immediately until 30 minutes or 3 hours after end of exposure in all 5 of 5 male and 5 of 5 female animals. None of the animals died prematurely. All animals gained the expected body weight. No pathological findings were noted at necropsy.
Therefore, LC50 of test item for rats is greater than 5.07 mg/L air for 4 hour.
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