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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 941-432-8 | CAS number: 1085706-46-2
- 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:
- August 6th, 2007 to September 19th, 2007
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Study was conducted according to OECD and in accordance with GLP. The study material is well characterized
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 007
- Report date:
- 2007
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- EU method B.47 (Bovine corneal opacity and permeability test method for identifying ocular corrosives and severe irritants)
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)
- GLP compliance:
- yes
Test material
- Reference substance name:
- tert-butyl (2S)-2-[5-(4'-{2-[(2S)-1-[(tert-butoxy)carbonyl]pyrrolidin-2-yl]-1H-imidazol-5-yl}-[1,1'-biphenyl]-4-yl)-1H-imidazol-2-yl]pyrrolidine-1-carboxylate
- EC Number:
- 941-432-8
- Cas Number:
- 1085706-46-2
- Molecular formula:
- C36 H44 N6 O4
- IUPAC Name:
- tert-butyl (2S)-2-[5-(4'-{2-[(2S)-1-[(tert-butoxy)carbonyl]pyrrolidin-2-yl]-1H-imidazol-5-yl}-[1,1'-biphenyl]-4-yl)-1H-imidazol-2-yl]pyrrolidine-1-carboxylate
- Test material form:
- solid: particulate/powder
- Remarks:
- migrated information: powder
- Details on test material:
- White powder stored at room temperature and protected from exposure to light.
Constituent 1
Test animals / tissue source
- Species:
- other: Bovine
- Strain:
- not specified
- Details on test animals or tissues and environmental conditions:
- Bovine eyes were obtained froma local abattoir as a by-product from freshly slaughtered animals (J.W. TREUTH & SONS, Inc. Baltimore, MD). The eyes
were excised and then placed in Hanks' Balanced Salt Solution, containing Penicillin/Streptomycin (HBSS), and transported to the laboratory on ice
packs. Immediately upon receipt of the eyes in the laboratory, preparation of the corneas was initiated.
Test system
- Vehicle:
- physiological saline
- Controls:
- yes
- Amount / concentration applied:
- As instructed by the Sponsor, the test article was administered to the test system as a 20% (w/v) dilution in 0.9% USP saline. The test article dilution
was prepared by weighing 1211 mg of the test article into a prelabeled conical tube. Saline was added until a 20% (w/v) dilution was achieved and the
conical was vortexed for approximately 1 min. prior to application. - Duration of treatment / exposure:
- Treatment of corneas
Immediately prior to treatment, the medium was removed from the anterior compartment of the
holder using a pipette tip attached to a vacuum pump. Seven hundred and fifty µl (750 µl) of test substance, negative control (0.9%
sodium chloride solution) or positive control material (Imidazole 20% w/w solution) was
introduced in to the anterior part of the holder. The test substance at 20% w/w formed a white
paste and was added to the anterior compartment using a 2 ml syringe with the end cut off. The
test substance was applied via the anterior window and gently spread over the cornea with a
spatula. Following application the anterior compartment was plugged.
For the negative and positive control the holder was slightly rotated to ensure uniform distribution of the test
substance over the surface of the cornea. Each holder was then incubated in a horizontal position
at 32°C ± 2°C for 4 hours ± 5 minutes in a waterbath.
Following incubation, the test substance was removed and the epithelial surface of the cornea
washed, at least three times or until the wash medium was clear, with cMEM added via the holes
on the top of the holder. After each wash, the wash medium was removed using a pipette tip
attached to a vacuum pump. For the test substance, the anterior window was removed and the
cornea gently washed five times. The anterior window was then replaced. Following
completion of the wash step, the medium was removed from both compartments which were refilled
with fresh cMEM. The posterior compartment was re-plugged and the opacity of each
cornea measured and recorded. The opacity values obtained at this stage were used in
calculating the final In Vitro Irritancy Score. - Observation period (in vivo):
- Opacity measurements performed immediately after exposure period ends.
- Number of animals or in vitro replicates:
- 5 corneas
- Details on study design:
- After the tratment of the corneas, described above, the opacity of each cornea measured and recorded. The opacity values obtained at this stage were used in calculating the final In Vitro Irritancy Score.
The next stage is to perform the permeability assay:
Following the final opacity measurement, the medium was removed from the anterior compartment of the holder. One ml (1ml) of the sodium fluorescein solution was added to the anterior compartment using a micropipette, the compartment was plugged and the corneas incubated in a horizontal position at 32°C ± 2°C for 90 ± 5 minutes in a waterbath.
Followingthis incubation, the medium in the posterior compartment was mixed by drawing approximately 2.5 ml gently up and down a 5 ml syringe, with a needle attached, three times. An aliquot of the mixed medium from the posterior compartment was removed and transferred to a 1cm path length cuvette.
A spectrophotometer was adjusted to read at 490nm (OD490) and a sample of cMEM read (OD =0.065). The spectrophotometer was blanked using this solution prior to reading the permeability samples. Any solution giving an OD490 value above 1.8 was diluted 1 in 5 with cMEM.
Results and discussion
In vivo
Resultsopen allclose all
- Irritation parameter:
- other: Cornea opacity
- Basis:
- mean
- Time point:
- other: 4 hrs.
- Score:
- 8.5
- Irritation parameter:
- other: Permeability
- Basis:
- mean
- Time point:
- other: 4 hrs.
- Score:
- 0.002
- Irritation parameter:
- other: In Vitro Score
- Basis:
- mean
- Time point:
- other: 4 hrs.
- Score:
- 8.5
Any other information on results incl. tables
- The change in the opacity of each cornea was calculated by subtracting the initial basal opacity from the post-treatment opacity measurement.
- The mean change in opacity for the negative control corneas was calculated and was subtracted from the change in opacity of each treated cornea to obtain the corrected opacity value.
- The mean corrected opacity change value of each treatment group (of three corneas) was calculated from the individual corrected opacity values of the treated corneas.
- The corrected permeability value (OD490) of each treated cornea was calculated by subtracting the mean negative control cornea value from the permeability value of each cornea.
- The mean corrected permeability value of each treatment group was calculated from the individual corrected permeability values of the treated corneas.
- In Vitro Irritancy Score = Corrected Opacity Value + (15 x Corrected OD490 Value)
- The In Vitro Irritancy Score was calculated for each individual treatment and positive control cornea.
- The mean In Vitro IrritancyScore value for each treatment group was calculated from the In Vitro IrritancyScores of each individual cornea in the treatment group.
The pH of the test sample formulation, measured using universal pH sticks, was approximately 4.5
Opacity:
Permeability:
The In Vitro Irritancy Score was calculated using the following formula:
A substance that induces an IVIS ≥ 55.1 is defined as a corrosive or severe irritant.
Applicant's summary and conclusion
- Interpretation of results:
- slightly irritating
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- The test article recorded having an in vitro score of 8.5, classifying it as a mild irritant per criteria of test method.
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.