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EC number: 604-045-2 | CAS number: 137862-53-4
- 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 vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Aug 1992
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 992
- Report date:
- 1992
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- The rum of this ex-periment was to obtain information on the local tolerance of rabbits (pigmented Himalayan) to CGP 48933 (ex tempore), batch no. 800291, during short-term administration into the conjunctival sac of the right eye. The rabbits were also examined for their systemic reactions. As control animals, further rabbits were used which were treated \\oith 0.9% sodium chloride solution, batch no. 914425, abbreviated to 'Control'.
The present paper reports on the results of an experiment m which either a 0.5% solution or a 2.0% solution of CGP 43933 was instilled into the conjunctival sac of the right eye of rabbits for a period of 5 days. The solutions were prepared according to the sponsor's instructions and administered at a volume of 50 pi/animal .either 4 times/day at intervals of 90 minutes or 8 times/day at intervals of 45 minutes.
The study was performed in compliance \\oith the principles of 'Good Laboratory Practice' regulations (cf Management Statement, QAU Statement and the 'enclosure' for details). - GLP compliance:
- yes
Test material
- Reference substance name:
- N-Pentanoyl-N-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-L-valine
- EC Number:
- 604-045-2
- Cas Number:
- 137862-53-4
- Molecular formula:
- C24 H29 N5 O3
- IUPAC Name:
- N-Pentanoyl-N-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-L-valine
Constituent 1
Test animals / tissue source
- Species:
- rabbit
- Strain:
- Himalayan
- Details on test animals or tissues and environmental conditions:
- 12 male and 12 female pure-bred pigmented Himalayan rabbits aged approximately 4 months were used for this experiment (breeder: CHR.F. LEUSCHNER & Co., D-2355 Löhndorf).
Initial body weight at the start of treatment was 2.1 to 2.4 kg (males) and 2.2 to 2.6 kg (females). Animals were identified by ear tattoo and cage number.
Each rabbit received a continuous number from the breeding station Löhndorf.
Food, water and accommodation
ALTROMIN 2023 served as food. Periodic analyses of the food for contaminants are carried out at least tv.ice a year by the Landv:irtschaftliche Untersuchungs- und Forschungsanstalt · Kiel, Gutenbergstral3e 75 - 77, D-2300 Kiel 1. This food was offered ad lib. Food residue was removed and weighed.
All analyses are performed based on EPA/USA, Proposed Health Effects Test Standards for Toxic Substances Control Act Test Rules, Federal Register, 44, 27334 - 27375, May 1979_ The results were \\ithin the admissible limits.
Tap water was also given unrestrictedly (in drinking bottles). Samples of the water are analysed regularly (twice a year) by Medizinisches Zentral-Laboratorium, Lauenburger Str. 65, D-2054 Geesthacht.
Test system
- Vehicle:
- other: (100 mM Na2HPO4 + 50 mM 0.9% NaCl solution + 10 N NaOH
- Controls:
- yes, concurrent negative control
- Amount / concentration applied:
- Group 2:
50 ul CGP 48933 (ex tempore) (0.5% solution) referred to in this report as 0.5% CGP 48933
4 instillations/animal/day at intervals of 90 minutes
Group 3:
50 ul CGP 48933 (ex tempore) (2.0% solution), referred to in this report as 2% CGP 48933
4 instillations/animal/day at intervals of 90 minutes
Group 4:
50 ul CGP 48933 (ex tempore) (2.0% solution), referred to in this report as 2% CGP 48933
8 instillations/animal/day at intervals of 45 minutes
Group 1: Control
50 ul 0.9% NaCl solution (control solution)
8 instillations/animal/day at intervals of 45 minutes - Duration of treatment / exposure:
- 5 days
- Observation period (in vivo):
- 5days
- Number of animals or in vitro replicates:
- 24 (12 male and 12 female) rabbits
four groups each containing 3 male and 3 female rabbits - Details on study design:
- Route of administration: into the conjunctival sac of the right eye; the left eye remained untreated
Treatment vwith 50 ul 0.5% CGP 48933/animal 4 times per day, or with 50 ul 2% CGP 48933/animal 4 or 8 times per day,
or with 50 ul 0.9% NaCl solution/animal 8 times per day into the conjunctival sac of the right eye did not cause any substancerelated intolerance reactions in the eye and the optic region during or after 5 test days.
Results and discussion
In vivo
Resultsopen allclose all
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 4
- Reversibility:
- fully reversible
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- fully reversible
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 4
- Reversibility:
- fully reversible
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- fully reversible
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 4
- Reversibility:
- fully reversible
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- fully reversible
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- iris score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- fully reversible
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- iris score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- fully reversible
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- iris score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- fully reversible
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- chemosis score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- fully reversible
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- chemosis score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- fully reversible
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- chemosis score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- fully reversible
- Remarks on result:
- no indication of irritation
- Irritant / corrosive response data:
- The study was 5-day ocular tolerance study, not only 72 as indicated in the table (due to validation).
Any other information on results incl. tables
During the 5 - day treatment, the conjunctivae of each animal were examined on a daily basis before the first and after the last instillation.
Redness (grade 1 or 2 based on BALDWIN) was detected as follows TD5 and/or 6:
Group 1: 50 ul 0.9% NaCl solution/animal, 8 instillations/day (control)
no. 2 m left untreated eye grade 1
no. 5 f left untreated eye, right treated eye grade 1
Group 2: 50 ul 0.5% CGP 48933/animal, 4 instillations/day
no. 2m right treated eye grade 2
no. 3m left untreated eye grade 1
no. 4 f left untreated eye grade 1
Group 3: 50 ul 2% CGP 48933/animal, 4 instillations/day
no. 5 f left untreated eye grade 1
no. 6f left untreated eye grade 1
Opacity of the cornea (grade 1 based on BALDWIN) was observed animals in the treated right eye only, TD5 and/or 6:
Group 1: 50 ul 0.9% NaCl solution/animal, 8 instillations/day (control)
no. 1 m right treated eye grade 1
Group 3: 50 ul 2% CGP 48933/animal, 4 instillations/day
no. 5 f right treated eye grade 1
Group 4: 50 ul2% CGP 48933/animal, 8 instillations/day
no. 5 f right treated eye grade 1
no. 6 f left untreated eye, right treated eye grade 1
The fluorescein test resulted in slight staining (grade 1) in 50% of the cornea in one control animal (50 ,ul 0.9% NaCl solution/animal, 8 instillations/day) during both of the examinations on test day 5 and moderate staining (grade 2) in 50% of the cornea during the examination carried out on test day 6.
The fluorescein tests were negative in all other animals.
The iris was inconspicuous during the examinations. The anterior chamber and lens were inconspicuous in all 24 rabbits from all 4 groups at the various examination dates. The same was also true for the fundus of the eyes.
Miosis, mydriasis and/or ptosis were not observed.
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Under the present test conditions, treatment for 5 days with 50 ul 05% CGP 48933/animal, by instillation into the conjunctival sac of the right eye of rabbits - 4
times/day, or wiith 50 ul 2% CGP 48933/animal, administered 4 or 8 times/day, resulted in no local or systemic substance-related macroscopic intolerance reactions. Ophthalmological and ophthalmopathological examination of the eyes revealed no changes which are considered to be related to the instillation of the test substance CGP 48933.
Furthermore, other organs revealed no substance-related changes.
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