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EC number: 816-314-3 | CAS number: 927881-65-0
- 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:
- 11 June - 23 June 2017
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 017
- Report date:
- 2017
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.2400 (Acute Eye Irritation)
- Qualifier:
- according to guideline
- Guideline:
- other: EC No 440/2008, part B: "Acute Toxicity: Eye Irritation/Corrosion"
- Qualifier:
- according to guideline
- Guideline:
- other: JMAFF Guidelines (2000), including the most recent revisions
- GLP compliance:
- yes (incl. QA statement)
Test material
- Reference substance name:
- Methyl (1R,3S,4R,5R)-3-{[(2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl)carbonyl]amino}-5-({2,4,6-tri-O-benzoyl-3-O-[(2S)-1-(benzyloxy)-3-cyclohexyl-1-oxopropan-2-yl]-β-Dgalactopyranosyl}oxy)-4-[(2,3,4-tri-O-benzyl-6-deoxy-α-L-galactopyranosyl)oxy]cyclohexanecarboxylate
- EC Number:
- 816-314-3
- Cas Number:
- 927881-65-0
- Molecular formula:
- C83H87N3O21
- IUPAC Name:
- Methyl (1R,3S,4R,5R)-3-{[(2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl)carbonyl]amino}-5-({2,4,6-tri-O-benzoyl-3-O-[(2S)-1-(benzyloxy)-3-cyclohexyl-1-oxopropan-2-yl]-β-Dgalactopyranosyl}oxy)-4-[(2,3,4-tri-O-benzyl-6-deoxy-α-L-galactopyranosyl)oxy]cyclohexanecarboxylate
- Test material form:
- solid: particulate/powder
- Details on test material:
- White solid
Test item storage: At room temperature
Constituent 1
- Specific details on test material used for the study:
- White solid
Test item storage: At room temperature
Batch: 902/6460031/D/13/1 (is same batch as batch E010017351 on Certificate of Analysis)
Test animals / tissue source
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- Species: Rabbit
Strain: New Zealand White
Condition: SPF-Quality
Source: Charles River France, L’Arbresle, France
Number of Animals: 3 Males.
Age at the Initiation of Dosing: Young adult animals (approximately 12 weeks old) were selected.
Weight at the Initiation of Dosing: 2694 to 2929g.
Animal Identification:
At study assignment, each animal was identified using an ear mark with indelible ink.
Environmental Acclimation:
The animals were allowed to acclimate to the Test Facility toxicology accommodation for at least 5 days before the commencement of dosing.
Housing:
On arrival and following assignment to the study, animals were housed individually in labeled cages with perforated floors equipped with water bottles. These housing conditions were maintained unless deemed inappropriate by the Study Director and/or Clinical Veterinarian. The room(s) in which the animals were kept were documented in the study records. Each cage was clearly labeled.
Environmental Conditions:
Target temperatures of 18 to 24°C with a relative target humidity of 40 to 70% were maintained. The actual daily mean temperature during the study period was 19 to 20°C with an actual daily mean relative humidity of 56 to 95%. A 12-hour light/12-hour dark cycle was maintained. Ten or greater air changes per hour with 100% fresh air (no air recirculation) were maintained in the animal rooms.
Food:
Pelleted diet for rabbits was provided once daily throughout the study. In addition, hay was available during the study period.
Water:
Municipal tap-water was freely available to each animal via water bottles.
Test system
- Vehicle:
- unchanged (no vehicle)
- Controls:
- yes
- Amount / concentration applied:
- Animals were treated by instillation of, on average, 34.9 mg (range 34.8 – 35.3 mg) of the test item (a volume of approximately 0.1 mL), in the conjunctival sac of one of the eyes after gently pulling the lower lid away from the eyeball.
- Duration of treatment / exposure:
- 1 hr.
- Observation period (in vivo):
- Observations were made 1, 24, 48 and 72 hours after instillation.
- Number of animals or in vitro replicates:
- 3 males
- Details on study design:
- The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner 1 week later, after considering the degree of eye irritation observed in the first animal.
Pre-emptive Pain Management:
One hour prior to instillation of the test item, buprenorphine (Buprenodale®) 0.01 mg/kg was administered by subcutaneous injection in order to provide a therapeutic level of systemic analgesia.
Five minutes prior to instillation of the test item, two drops of the topical anaesthetic 0.5% proparacaine hydrochloric ophthalmic solution (Alcaine eye drops®) were applied to both eyes.
Administration of Test item:
Animals were treated by instillation of, on average, 34.9 mg (range 34.8 – 35.3 mg) of the test item (a volume of approximately 0.1 mL), in the conjunctival sac of one of the eyes after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test item. The other eye remained untreated and served as the reference control.
Immediately after the 1 hour observation, the treated eye was rinsed with approximately 50 mL tepid tap water, using a velocity of flow which did not affect the eye, to remove any visible residual test item. For reference control the other eye was also rinsed.
Immediately after the 24-hour observation, a solution of 2% fluorescein in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. Immediately after fluorescein examination on Day 2, in order to provide a continued level of systemic analgesia, buprenorphine 0.01 mg/kg and meloxicam 0.5 mg/kg were administered by subcutaneous injection.
Justification of Route and Dose Level:
The ocular route was selected because the test item may accidentally come into contact with the eyes during manufacture, handling and/or use. The dose level was based on the test guidelines.
Mortality/Moribundity Checks:
Throughout the study, animals were observed for general health/mortality and moribundity twice daily, in the morning and at the end of the working day. Animals were not removed from cage during observation, unless necessary for identification or confirmation of possible findings.
Postdose Observations:
Postdose observations were performed once daily throughout the study, the observation period was 72 hours.
All the animals were examined for reaction to dosing. The onset, intensity and duration of these signs was recorded (if appropriate), particular attention being paid to the animals during and for the first hour after dosing.
Body Weights:
Animals were weighed individually on Day 1 (predose) and on the day of the final observation
Irritation:
The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after instillation of the test item. The irritation scores and a description of all other (local) effects were recorded.
Terminal Procedures:
After the final observation, the animals were sacrificed by intra-venous injection of Euthasol® 20%.
Results and discussion
In vivo
Resultsopen allclose all
- Irritation parameter:
- cornea opacity score
- Basis:
- animal: 260
- Time point:
- 24/48/72 h
- Score:
- 0
- Reversibility:
- fully reversible
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- cornea opacity score
- Basis:
- animal: 273
- Time point:
- 24/48/72 h
- Score:
- 0
- Reversibility:
- fully reversible
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- cornea opacity score
- Basis:
- animal: 274
- Time point:
- 24/48/72 h
- Score:
- 0
- Reversibility:
- fully reversible
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- iris score
- Basis:
- animal: 260
- Time point:
- 24/48/72 h
- Score:
- 0
- Reversibility:
- fully reversible
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- iris score
- Basis:
- animal: 273
- Time point:
- 24/48/72 h
- Score:
- 0
- Reversibility:
- fully reversible
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- iris score
- Basis:
- animal: 274
- Time point:
- 24/48/72 h
- Score:
- 5
- Reversibility:
- fully reversible within: 24 hrs.
- Remarks on result:
- positive indication of irritation
- Irritation parameter:
- conjunctivae score
- Basis:
- animal: 260
- Time point:
- 24/48/72 h
- Score:
- 6
- Reversibility:
- fully reversible within: 24 hrs.
- Remarks on result:
- positive indication of irritation
- Irritation parameter:
- conjunctivae score
- Basis:
- animal: 273
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 6
- Reversibility:
- fully reversible within: 48 hrs.
- Remarks on result:
- positive indication of irritation
- Irritation parameter:
- conjunctivae score
- Basis:
- animal: 274
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 6
- Reversibility:
- fully reversible within: 48 hrs.
- Remarks on result:
- positive indication of irritation
- Irritant / corrosive response data:
- There was no evidence of ocular corrosion.
- Other effects:
- Coloration / Remnants:
Remnants of the test item were present in the eye on Day 1.
Toxicity / Mortality:
No signs of systemic toxicity were observed in the animals during the test period and no mortality occurred.
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Instillation of the test item resulted in effects on the iris and conjunctivae. Iridial irritation was observed in one animal and resolved within 24 hours. The irritation of the conjunctivae consisted of redness, chemosis and discharge and completely resolved within 24 hours in one animal and within 48 hours in the other two animals. Remnants of the test item were present in the eye on Day 1.
- Executive summary:
Based on the maximum group mean of 7.7, PF-06460260 is classified as minimal irritant to the rabbit eye according to the Kay and Calandra classification system.
Based on these results, PF-06460260 does not have to be classified and has no obligatory labelling requirement for eye irritation according to the:
• Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments).
• Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).
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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