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EC number: 810-753-4 | CAS number: 1374639-78-7
- 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:
- Feb - May 2014
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 014
- Report date:
- 2014
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.2600 (Skin Sensitisation)
- GLP compliance:
- yes
- Type of study:
- mouse local lymph node assay (LLNA)
Test material
- Reference substance name:
- tert-Butyl 4-({6-[7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino}pyridin-3-yl)piperazine-1-carboxylate
- EC Number:
- 810-753-4
- Cas Number:
- 1374639-78-7
- Molecular formula:
- C28H38N8O3
- IUPAC Name:
- tert-Butyl 4-({6-[7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino}pyridin-3-yl)piperazine-1-carboxylate
- Test material form:
- solid: bulk
Constituent 1
In vivo test system
Test animals
- Species:
- mouse
- Strain:
- Balb/c
- Sex:
- female
- Details on test animals and environmental conditions:
- Animal species and strain: Mouse, Balb/c strain, inbred, SPF-Quality.
Breeder/supplier: Charles River Deutschland, Sulzfeld, Germany.
Number of animals 30 females (nulliparous and non-pregnant), six females per group.
Age: Approximately 9 weeks (at initiation of treatment).
Body weight range: 17 to 20 gram (at initiation of treatment).
Health Check: A health inspection was performed prior to treatment, to ensure that the animals are in a good state of health. Special attention was paid to the ears, which were intact and free from any abnormality.
Study design: in vivo (LLNA)
- Vehicle:
- other: DAE433 (Merck, Darmstadt, Germany)
- Concentration:
- Concentrations of 25% and 50% were tested and the highest concentration was the maximum concentration as required in the test guidelines (50% for solids).
- No. of animals per dose:
- Three groups of six animals were treated with one test item concentration per group. The highest test item concentration was selected from the pre-screen test. One group of six animals was treated with vehicle and one group with the positive control item.
- Details on study design:
- Induction - Days 1, 2 and 3
For the experimental animals, the dorsal surface of both ears was epidermally treated (25 μL/ear) with the test item concentration, approximately the same time each day. The concentrations were mixed thoroughly using a magnetic stirrer immediately prior to dosing.
The control animals were treated as described for the experimental animals, except that, instead of the test item, the vehicle or positive control item was administered. - Positive control substance(s):
- other: 0.5% 1-Chloro-2,4-Dinitrobenzene (DNCB)
- Statistics:
- Calculations were performed in MS EXCEL and statistical analysis was performed with GraphPad Prism 4 (Kruskal-Wallis test, followed by the Mann Whitney test).
Results and discussion
- Positive control results:
- The positive control item DNCB elicited a reaction pattern with increased LN hyperplasia, which was in congruence with the expected mode of action of a contact allergen.
In vivo (LLNA)
Resultsopen allclose all
- Key result
- Parameter:
- other: Ear weight index
- Value:
- ca. 1.13
- Test group / Remarks:
- 0.5% LEE011-A3
- Key result
- Parameter:
- other: Ear weight index
- Value:
- ca. 1.1
- Test group / Remarks:
- 5% LEE011-A3
- Key result
- Parameter:
- other: Ear weight index
- Value:
- ca. 1.05
- Test group / Remarks:
- 50% LEE011-A3
- Key result
- Parameter:
- other: LN weight index
- Value:
- ca. 1.19
- Test group / Remarks:
- 0.5% LEE011-A3
- Key result
- Parameter:
- other: LN weight index
- Value:
- ca. 1.16
- Test group / Remarks:
- 5% LEE011-A3
- Key result
- Parameter:
- other: LN weight index
- Value:
- ca. 1.17
- Test group / Remarks:
- 50% LEE011-A3
- Key result
- Parameter:
- other: Cell count index
- Value:
- ca. 1.04
- Test group / Remarks:
- 0.5% LEE011-A3
- Key result
- Parameter:
- other: Cell count index
- Value:
- ca. 1.2
- Test group / Remarks:
- 5% LEE011-A3
- Key result
- Parameter:
- other: Cell count index
- Value:
- ca. 1.44
- Test group / Remarks:
- 50% LEE011-A3
- Key result
- Parameter:
- SI
- Test group / Remarks:
- LEE011-A3: 0.5% (w/w)
- Remarks on result:
- not measured/tested
- Key result
- Parameter:
- SI
- Test group / Remarks:
- LEE011-A3: 5%
- Remarks on result:
- not measured/tested
- Key result
- Parameter:
- SI
- Test group / Remarks:
- LEE011-A3: 50% (w/w)
- Remarks on result:
- not measured/tested
- Cellular proliferation data / Observations:
- LEE011-A3 exceeded the ear weight threshold at all concentrations with statistical significance at 0.5% and 5% when compared to vehicle. No clear dose response was found.
LEE011-A3 did not cause any relevant changes in LN weight up to a concentration of 50% in DAE433.
LEE011-A3 exceeded the LN count threshold at 50% with statistical significance when compared to vehicle and showed a clear dose response.
Any other information on results incl. tables
No irritation of the ears was noted after visual examination in the majority of animals. Brown testsubstance remnants on the dorsal surface of the ears of the animals treated at 50% (between Days 1-3) did not hamper scoring for erythema. Visual examination of the nodes revealed that all the nodes of the experimental animals were considered normal in size when compared to the vehicle control group. No macroscopic abnormalities of the surrounding areas were noted in any of the animals.
Body weights and body weight gain of experimental animals remained in the same range as controls over the study period. There were no clinical observations attributable to treatment with LEE011-A3.
Applicant's summary and conclusion
- Interpretation of results:
- Category 1B (indication of skin sensitising potential) based on GHS criteria
- Conclusions:
- In conclusion, LEE011-A3 appeared to be a weak sensitizer with weak irritating potential in the murine LLNA TIER I.
Based on these results:
according to the recommendations made in the test guidelines (including all amendments), LEE011-A3 would be regarded as skin sensitizer.
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