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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 939-657-1 | CAS number: -
- 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
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 011
- Report date:
- 2011
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 403 (Acute Inhalation Toxicity)
- Version / remarks:
- (2009)
- Qualifier:
- according to guideline
- Guideline:
- other: OECD Guidance Document No. 39 (2009)
- GLP compliance:
- yes (incl. QA statement)
- Test type:
- standard acute method
- Limit test:
- no
Test material
- Reference substance name:
- HDI oligomers, allophanate
- EC Number:
- 939-657-1
- Molecular formula:
- not applicable (UVCB substance)
- IUPAC Name:
- HDI oligomers, allophanate
- Test material form:
- liquid
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Strain: Hsd Cpb:WU (SPF) wistar strain
- Source: Harlan-Nederland, AD Horst, Netherlands
- Age at study initiation: approximately 2 months
- Weight at study initiation: males: 178 - 187 g; females: 168 - 183 g
- Housing: singly in conventional Makrolon Type IIIH cages
- Diet: standard fixed-formula diet (KLIBA 3883), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 40 - 60
- Air changes (per hr): approximately 10
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- inhalation: aerosol
- Type of inhalation exposure:
- nose only
- Vehicle:
- air
- Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Plexiglas exposure restrainers (TSE, Bad Homburg, Germany)
- Mode of exposure: Animals were exposed to the aerosolized test article in restrainers made of Plexiglas. Restrainers were chosen that accomodated the animals' size. Each inhalation chamber segment was suitable to accomodate 20 rats at the perimeter location. The design of the directed-flow inhalation chamber minimizes re-breathing of exhaled test atmosphere. For validation see Pauluhn, Journal of Applied Toxicology 14, 1994, 55-62 and Pauluhn & Thiel, Journal of Applied Toxicology 27, 2007, 160-167.
- Source and rate of air: Dry conditioned air, 15 L/min
- Method of conditioning air: Compressed air was supplied by Boge compressors and was conditioned (free from water dust and oil) automatically by a VIA compressed air dryer.
- System of generating particulates/aerosols: Under dynamic conditions the targeted concentrations were achieved by atomization using the nozzle-baffle system and inhalation chamber. For atomization a binary nozzle (Schlick water jacketed nozzle which was connected to a thermostat, 25°C, using a digitally controlled water bath) and conditioned compressed air was used (15 L/min). The representative dispersion pressure was approximately 600 kPa. The test article was fed into the nozzle system using a digitally controlled infusion pump (Harvard PHD 2000 infusion pump).
- Optimization of respirability: In order to increase the efficiency of the generation of fine particles likely to evaporate and to prevent larger particles from entering the chamber a glass-pre-separator/baffle system was used.
- Inhalation chamber equilibrium concentration: The test atmosphere generation conditions provide an adequate number of air exchanges per hour (15 L/min x 60 min/(3.8 L) = 237, continuous generation of test atmosphere). Under such test conditions used chamber equilibrium is attained in less than one minute of exposure. At each exposure port a minimal air flow rate of 0.75 I/min was provided. The test atmosphere can by no means be diluted by bias-air-flows.
- Method of particle size determination: Cascade impactor (Berner critical orifice cascade impactor)
- Treatment of exhaust air: The exhaust air was purified via filter systems.
- Temperature, humidity: Temperature and humidity measurements were performed by the computerized Data Acquisition and Control System using HC-S3 sensors (Rotronic). The position of the probe was at the exposure location of rats. Mean temperatures from 20.7 to 22°C, 5% relative humidity.
TEST ATMOSPHERE
- The integrity end stability of the aerosol generation and exposure system was measured by using a RAS-2 real-time aerosol photometer (MIE, Bedford, Massachusetts, USA).
- Brief description of analytical method used: gravimetric analysis of filter samples (filter: Glass-Fibre-Filter, Sartorius, Göttingen, Germany; digital balance).
- Samples taken from breathing zone: yes
- Particle size distribution: The particle size distribution was analyzed using a BERNER critical orifice cascade impactor. Aerosol mass < 3 µm: 87.5% for 235 mg/m³, 86.9% for 284 mg/m³, 84.6% for 314 mg/m³.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): The aerosol was generated so that it was respirable to rats, i.e. the average mass median aerodynamic diameter (MMAD) was 1.8 µm, the average geometric standard deviation (GSD) was approx. 1.6. - Analytical verification of test atmosphere concentrations:
- yes
- Duration of exposure:
- 4 h
- Concentrations:
- Target concentrations: 200 mg/m³, 275 mg/m³, 300 mg/m³
Analytical concentrations: 235 mg/m³, 284 mg/m³, 314 mg/m³ - No. of animals per sex per dose:
- 5
- Control animals:
- yes
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The appearance and behavior of each rat were examined carefully several times on the day of exposure and at least once daily thereafter. Weekend assessments were made once a day (morning). Assessments from restraining tubes were made only if unequivocal signs occurred (e.g. spasms, abnormal movements, and severe respiratory signs). Body weights were measured before exposure, on days 1, 3 and 7, and weekly thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: Reflexes were tested (visual placing response, grip strength on wire mesh, abdominal muscle tone, corneal and pupillary reflex, pinnal reflex, righting reflex, tail-pinch response, startle reflex with respect to behavioral changes stimulated by sounds (finger snapping) and touch (back).
Rectal temperatures were determined shortly after cessation of exposure. - Statistics:
- Analysis of variance (ANOVA) was used for statistical evaluation.
Calculation of LC50 was performed according to Rosiello et al. (1977; Rosiello, Essigmann and Wogan, Tox and Environ. Health, 3, pp797) as modified by Pauluhn (1983). It is based on the maximum likelihood method of Bliss (1983; Q.J.Pharm.Pharmacol., 11, pp192).
Results and discussion
Effect levelsopen allclose all
- Sex:
- male
- Dose descriptor:
- LC50
- Effect level:
- 264 mg/m³ air
- 95% CL:
- 240.53 - 290.7
- Exp. duration:
- 4 h
- Sex:
- female
- Dose descriptor:
- LC50
- Effect level:
- > 314 mg/m³ air
- Exp. duration:
- 4 h
- Mortality:
- No animal died in the lowest dose group of 235 mg/m³. Mortality occured at 284 mg/m³ and higher (4 males and 2 females at 284 mg/m³, 5 males and 1 female at 314 mg/m³). Rats succumbed on the exposure day or were found dead in the morning of the first postexposure day.
- Clinical signs:
- other: see "Other findings"
- Body weight:
- Treated animals showed transient reduced body weights as compared to control animals.
- Gross pathology:
- Necropsy of animals that died during the study revealed nasal/muzzle with red encrustations, nostrils with foamy content/discharge, lung less collapsed with foamy whitish content in trachea, hydrothorax, abdomen bloated and discoloration/bloodless appearance of parenchymatous organs.
Necropsy of surviving animals at the end of the study period did not reveal any abnormal finding compared to control. - Other findings:
- All treated animals showed significantly reduced rectal temperatures (hypothermia).
A battery of reflex measurements was made on the first post-exposure day. ln comparison to the rats of the control group, substance treated rats exhibited impaired reflexes.
Clinical Signs:
Clinical observation showed evidence of respiratory irritation typical of lower respiratory tract sensory irritation. The following signs were observed (exposure day up to postexposure day 10): bradypnoea, labored breathing patterns, crepitations, irregular breathing patterns, motility reduced, atony, high-legged gait, tremor, gait uncoordinated, hair-coat ungroomed, piloerection, cyanosis, nasal discharge (serous), nose red encrustations, muzzle red encrustrations, stridor, nostrils: red encrustrations, eye lids: red encrustrations, decreased body weights, decreased reflexes, and hypothermia.
Applicant's summary and conclusion
- Executive summary:
A study on the acute inhalation toxicity of the substance on rats was conducted in accordance with OECD TG 403. Test procedures were adapted so as to comply also with the EU Directive 92/69/EEC, and especially OECD GD39 (2009). Three groups of rats were nose-only exposed to the liquid aerosol of the test article in actual concentrations of 0, 235, 284 and 314 mg/m³. The aerosol was generated so that it was respirable to rats, i.e. the average mass median aerodynamic diameter (MMAD) was 1.8 µm, the average geometric standard deviation (GSD) was approx. 1.6.
Mortality occured at 284 mg/m³ and higher. Rats succumbed on the exposure day or were found dead in the morning of the first postexposure day. Clinical observation showed evidence of respiratory irritation typical of lower respiratory tract sensory irritation, e.g. bradypnoea, labored and irregular breathing patterns, reduced motility, atony, high-legged and uncoordinated gait, tremor, ungroomed hair-coat, piloerection, cyanosis, serous nasal discharge and encrustations of nose and eye.
For males the LC50 was determined to be 264 mg/m³. Females were found less susceptible than males, resulting in a LC50 of > 314 mg/m³. The NOAEL for both male and female rats was concluded to be < 235 mg/m³.
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.