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EC number: 606-195-4 | CAS number: 189956-45-4
- 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
Eye irritation
Administrative data
- Endpoint:
- eye irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- FRom 2004-11-01 to 2004-11-01
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Remarks:
- While only a study summary was available for review which provided limited details on the test substance and methodology, sufficient information was provided to deem the study reliable with restrictions.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 004
- Report date:
- 2004
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- The ocular irritancy potential of the test material was assessed using the rabbit enucleated eye test (REET) SPL Standard Test Method 569.04. This method involved the application of the test material onto the cornea of the enucleated eye.
- GLP compliance:
- no
- Remarks:
- The study was conducted in a facility operating to Good Laboratory Practice within the UK national GLP monitoring programme, but the study report had not been audited by the QA Unit. No formal claim of GLP compliance was made for the study.
Test material
- Reference substance name:
- 4-[(4-Oxo-1,4-dihydropyrimidin-2-yl)amino]benzonitrile
- EC Number:
- 606-195-4
- Cas Number:
- 189956-45-4
- Molecular formula:
- C11H8N4O
- IUPAC Name:
- 4-[(4-Oxo-1,4-dihydropyrimidin-2-yl)amino]benzonitrile
- Test material form:
- solid: particulate/powder
- Details on test material:
- - Name of test material (as cited in study report): JNJ-40370226-AAA (T002487)
- Physical state: solid (powder)
- Appearance: Off-white powder
Constituent 1
- Specific details on test material used for the study:
- no data
Test animals / tissue source
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- SOURCE OF COLLECTED EYES
- Source: New Zealand White rabbits, no further data on test animals
- Storage, temperature and transport conditions of ocular tissue (e.g. transport time, transport media and temperature, and other conditions): the enucleated eyes were maintained at a temperature of 32°C +/- 1.5°C within the superfusion apparatus.
Test system
- Vehicle:
- not specified
- Controls:
- yes, concurrent negative control
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL of the test item, which had been found to weigh approximately 60 mg
- Concentration (if solution): no data
NEGATIVE CONTROL
- Amount(s) applied (volume or weight with unit): No data
- Concentration (if solution): 0.9% - Duration of treatment / exposure:
- single application
- Number of animals or in vitro replicates:
- 3 enucleated eyes were treated with the test item and 2 enucleated eyes were treated with the control.
- Details on study design:
- REMOVAL OF TEST SUBSTANCE: no data
OBSERVATION TIME POINTS
- corneal opacity and corneal epithelium condition: 60, 120, 180 and 240 min post dosing
- fluorescein uptake: 240 min post dosing
- corneal swelling: 60, 120 and 240 min post dosing
SCORING SYSTEM:
The direct effect of the test substance on the cornea was assessed by evaluation of corneal thickness, corneal opacity, alteration of corneal epithelium and fluorescein uptake, throughout the duration of the study.
TOOL USED TO ASSESS SCORE:
no data
Results and discussion
In vitro
Resultsopen allclose all
- Irritation parameter:
- cornea opacity score
- Remarks:
- cloudiness/ mean of 3 eyes after 60, 120, 180 and 240 min post dosing
- Run / experiment:
- 1
- Value:
- 1
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- not applicable
- Remarks on result:
- positive indication of irritation
- Irritation parameter:
- cornea opacity score
- Remarks:
- area/mean of three eyes after 60, 120, 180 and 240 min post dosing
- Run / experiment:
- 1
- Value:
- 2.3
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- not applicable
- Irritation parameter:
- other: Fluorescein uptake
- Remarks:
- intensity/mean of three eyes
- Run / experiment:
- 1
- Value:
- 1
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- not applicable
- Remarks on result:
- positive indication of irritation
- Irritation parameter:
- other: Fluorescein uptake
- Remarks:
- area/mean of three eyes
- Run / experiment:
- 1
- Value:
- 2
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- not applicable
- Irritation parameter:
- percent corneal swelling
- Remarks:
- mean of three eyes 60 min post dosing
- Run / experiment:
- 1
- Value:
- 13.7
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- not applicable
- Remarks on result:
- positive indication of irritation
- Irritation parameter:
- percent corneal swelling
- Remarks:
- mean of three eyes 120 min post dosing
- Run / experiment:
- 1
- Value:
- 15.3
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- not applicable
- Remarks on result:
- positive indication of irritation
- Irritation parameter:
- percent corneal swelling
- Remarks:
- mean of three eyes 240 min post dosing
- Run / experiment:
- 1
- Value:
- 19.6
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- not applicable
- Remarks on result:
- positive indication of irritation
- Other effects / acceptance of results:
- negative control eyes:
- corneal opacity: 0 (mean of 2 eyes)
- corneal epithelium condition: normal (2 eyes)
- fluorescein uptake: 0 (mean of 2 eyes)
- corneal swelling: 1.0 at 60 min post dosing, 1.1 at 120 minutes post dosing and 1.3 at 240 minutes post dosing
Corneal epithelium condition was normal at all timepoints for all test item treated eyes.
Any other information on results incl. tables
Table 1. Results obtained for corneal opacity at 60, 120, 180, and 240 minutes post exposure.
|
Corneal Opacity |
|||||||
Observation Period (minutes post dosing) |
||||||||
60 |
120 |
180 |
240 |
|||||
Cldy |
Area |
Cldy |
Area |
Cldy |
Area |
Cldy |
Area |
|
Test Eyes |
1 |
3 |
1 |
4 |
1 |
4 |
1 |
4 |
1 |
3 |
1 |
2 |
1 |
1 |
1 |
1 |
|
1 |
2 |
1 |
2 |
1 |
1 |
1 |
1 |
|
Control Eyes |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Cldy = Corneal opacity
Table 2. Results obtained for corneal epithelium condition at 60, 120, 180, and 240 minutes post exposure.
|
Corneal Epithelium Condition |
|||
Observation Period (minutes post dosing) |
||||
60 |
120 |
180 |
240 |
|
Test Eyes |
Normal |
Normal |
Normal |
Normal |
Normal |
Normal |
Normal |
Normal |
|
Normal |
Normal |
Normal |
Normal |
|
Control Eyes |
Normal |
Normal |
Normal |
Normal |
Normal |
Normal |
Normal |
Normal |
Table 3. Results obtained for fluorescein uptake 240 minutes post exposure.
|
Fluorescein Uptake (240 minutes) |
||||
Test Eyes |
Control Eyes |
||||
Int |
1 |
1 |
1 |
0 |
0 |
Area |
4 |
1 |
1 |
0 |
0 |
Int = Intensity of fluorscein uptake
Table 4. Results obtained for corneal swelling at 60, 120, and 240 minutes post exposure.
|
Corneal Swelling (%)(minutes post dosing) |
||
60 |
120 |
240 |
|
Test Eyes |
13.7 |
15.3 |
19.6 |
Control Eyes |
1.0 |
1.1 |
1.3 |
Test eyes results are the mean of three eyes while control eyes are the mean of two eyes
Applicant's summary and conclusion
- Interpretation of results:
- Category 1 (irreversible effects on the eye) based on GHS criteria
- Conclusions:
- The test material is considered to have the potential to cause severe ocular irritancy in vivo.
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.
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