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Diss Factsheets
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EC number: 951-814-6 | 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
Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 10 September - 30 September 2019
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 019
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- GLP compliance:
- yes
- Type of study:
- mouse local lymph node assay (LLNA)
Test material
- Reference substance name:
- 4-(6-{3,6-diazabicyclo[3.1.1]heptan-3-yl}pyridin-3-yl)-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-carbonitrile
- Molecular formula:
- C22H24N6O2.[2]H2O4S
- IUPAC Name:
- 4-(6-{3,6-diazabicyclo[3.1.1]heptan-3-yl}pyridin-3-yl)-6-(2-hydroxy-2-methylpropoxy)pyrazolo[1,5-a]pyridine-3-carbonitrile
- Test material form:
- solid: particulate/powder
- Details on test material:
- Batch (Lot) Number: 18-547.25-002
Physical Description: White powder
Storage Conditions: Kept in a room temperature area, protected from light
Constituent 1
In vivo test system
Test animals
- Species:
- mouse
- Strain:
- CBA:J
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS:
Source: Jackson Laboratories, Bar Harbor, Maine.
Age at initiation of dosing: Approximately 8-9 weeks
Weight at initiation of dosing: 15.0 - 23.1 g
Housing: The animals were group-housed at receipt in solid bottom cages with nonaromatic bedding. Subsequently, the animals were individual housed.
Diet (e.g. ad libitum): PMI diet, ad lbitum.
Water (e.g. ad libitum): Ad lbitum.
Acclimation period: 8 - 15 days
ENVIRONMENTAL CONDITIONS:
Target Temperature (°C): 68 - 79 °F
Target Relative Humidity (%): 30% - 70%
Air changes (per hr): Ten or greater air changes per hour wiht 100% fresh air
Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark.
IN-LIFE DATES:
From:
Study design: in vivo (LLNA)
- Vehicle:
- dimethyl sulphoxide
- Concentration:
- 1, 4.5, 5, 10, 15, 25, and 45%.
- No. of animals per dose:
- Group 1: 2 mice: test material dose concentration: 1%, Group 2: 2 mice: test material dose concentration: 5%, Group 3: 2 mice: test material dose concentration 10%, Group 4: 2 mice: test material dose concentration: 25%, Group 5: 2 mice: test material dose concentration: 45%, Group 6: 5 mice: vehicle dose concentration 0%, Group 7: 5 mice: HCA dose concentration: 35%, Group 8: 5 mice: test material dose concentration: 4.5%, Group 9: 5 mice: test material concentration: 15%, Group 10: 5 mice: test material concentration: 45%.
- Details on study design:
- Phase 1: The test article was administered once daily for 3 days starting on Day 1 via dermal application to the outer ear using a micropipette.
Phase 2: The test article, positive control article, or vehicle were administered once daily (approximately ± 1 hour apart) for 3 days starting on Day 1 via dermal application to the outer ear using a micropipette. The cell proliferation marker article was administered once on Day 6 via IV injection.
For dermal administration, the vehicle, test article, and positive control article were withdrawn from stirred formulations.
Clinical observations:
Observations for clinical signs all animals were conducted daily starting on Day -1. Examinations on dosing days were performed approximately 2 to 4 hours postdose.
Body Weight:
Body weights for all animals were measured and recorded within 3 days of receipt, on Day 1 prior to dosing, and Day 6.
Study Termination:
At study termination, Phase 1 animals were euthanized by carbon dioxide inhalation followed by a Testing Facility SOP approved method to ensure death. The carcasses were discarded without further evaluation.
Terminal Procedures:
Postmortem study evaluations were performed on all Phase 2 animals at the scheduled terminal necropsy.
Tissue Sample Collection:
At the terminal necropsy, 5 hours following 3H methyl thymidine administration on Day 6, the auricular lymph nodes were collected from all surviving Phase 2 animals. The tissues were collected in a plastic container on wet ice and processed for radioanalysis. - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- The raw data were tabulated within each time interval, and the mean and standard deviation were calculated for each endpoint by sex and group. For each endpoint, treatment groups were compared to the control group. A group pair-wise comparison (general ANOVA) was performed.
Results and discussion
- Positive control results:
- The positive control group (35% HCA) resulted in a sensitization index (SI) of 4.34 which is indicative of a sensitizer (SI ≥3). In addition, the SI correlated well with the mean dpm values, which were significantly increased in the 35% HCA group relative to the vehicle group.
In vivo (LLNA)
Resultsopen allclose all
- Parameter:
- SI
- Value:
- 0.95
- Test group / Remarks:
- 4.5%
- Parameter:
- SI
- Value:
- 1
- Test group / Remarks:
- 15%
- Key result
- Parameter:
- SI
- Value:
- 4.74
- Test group / Remarks:
- 45%
Any other information on results incl. tables
Mortality: All animals survived to the scheduled necropsy except one animal in the positive control group (Animal No. 7503) administered 35% HCA that was euthanized in extremis on Day 3.
Radioactivity Analysis: The average radiochemical concentration of the formulation Group No. 6 was 2688505278 dpm/g.
Clinical Observations:
There were no significant findings or signs of local irritation in either the Irritation Screen or in the Main Study Phase for animals administered the vehicle or the test article. White discoloration of the skin (left and right ear) was observed in animals administered COM-1079 at 15 and 45%. Red discoloration of the skin (left and right ear), wet hair in the cervical region, and unkempt appearance was observed in all animals administered 35% HCA on Days 1 through 3. Animal No. 7503 (Group 7, 35% HCA) was observed with hunched posture and decreased activity on Day 3 and was euthanized in extremis.
Body Weight: There was no effect on body weight during the course of this study.
Lymph Node Radioanalysis: When COM-1079 formulations were compared to the vehicle the sensitization indices were 0.95, 1.00, and 4.74 for the formulations at 4.5%, 15%, and 45% for the test article groups, respectively.
Applicant's summary and conclusion
- Interpretation of results:
- Category 1B (indication of skin sensitising potential) based on GHS criteria
- Conclusions:
- COM-1079 formulations were determined to not be sensitizers at concentrations of 4.5 and 15% in the Murine Local Lymph Node Assay. COM-1079 formulations were determined to be sensitizers at a concentration of 45% in the Murine Local Lymph Node Assay.
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