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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 807-111-0 | CAS number: 1211441-98-3
- 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
Endpoint summary
Administrative data
Description of key information
Primary skin irritation/corrosion study with LEE011 -A4 in the rabbit (4-hour semi-occlusive application) showed that the substance has non-irritating effect.
The LEE011-A4 is potentially irritant or corrosive in the EpiOcular™ test under the experimental conditions described in this report. The test item is identified as potentially requiring classification and labelling according to UN GHS (Category 2 or Category 1).
Key value for chemical safety assessment
Skin irritation / corrosion
Link to relevant study records
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Nov 2103 - March 2104
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.2500 (Acute Dermal Irritation)
- GLP compliance:
- yes
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- Albino rabbit, New Zealand White, (SPF-Quality).
- Type of coverage:
- semiocclusive
- Preparation of test site:
- clipped
- Vehicle:
- water
- Controls:
- no
- Amount / concentration applied:
- Each animal was treated by dermal application of 0.5 grams of the test substance. The test substance was moistened with 0.6 mL of the vehicle and applied to the skin of one flank, using a metalline patch# of 2x3 cm.
- Duration of treatment / exposure:
- 4 h
- Observation period:
- The skin reactions were assessed at approximately 1, 24, 48 and 72 hours after the removal of the dressings and test substance.
- Number of animals:
- 3
- Irritation parameter:
- overall irritation score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- ca. 0
- Max. score:
- 0
- Reversibility:
- other: No skin irritation
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- overall irritation score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- ca. 0
- Max. score:
- 0
- Reversibility:
- other: No skin irritation
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- overall irritation score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- ca. 0
- Max. score:
- 0
- Reversibility:
- other: No skin irritation
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- erythema score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- erythema score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- erythema score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- edema score
- Basis:
- animal #1
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- edema score
- Basis:
- animal #2
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- edema score
- Basis:
- animal #3
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Remarks on result:
- no indication of irritation
- Irritant / corrosive response data:
- There was no evidence of a corrosive effect on the skin.
- Other effects:
- No staining of the treated skin by the test substance was observed and no test substance remnants were seen.
- Interpretation of results:
- other: No skin irritation was caused by 4 hours exposure to LEE011-A4..
- Conclusions:
- Based on the results LEE011-A4 does not have to be classified and has no obligatory labelling requirement for skin irritation
Reference
No skin irritation was caused by 4 hours exposure to LEE011-A4.
There was no evidence of a corrosive effect on the skin.
No staining of the treated skin by the test substance was observed and no test substance remnants were seen.
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Eye irritation
Link to relevant study records
- Endpoint:
- eye irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Nov 2017 - Feb 2018
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 492 (Reconstructed Human Cornea-like Epithelium (RhCE) Test Method for Identifying Chemicals Not Requiring Classification and Labelling for Eye Irritation or Serious Eye Damage)
- GLP compliance:
- yes
- Species:
- human
- Strain:
- other: EpiOcular tissue construct is a non-keratinized epithelium (0.6 cm2) prepared from normal human keratinocytes (MatTek)
- Details on test animals or tissues and environmental conditions:
- The EpiOcular tissue construct is a non-keratinized epithelium (0.6 cm2) prepared from normal human keratinocytes (MatTek). It models the cornea epithelium with progressively stratified, but not cornified cells. These cells are not transformed or transfected with genes to induce an extended life span in culture. The “tissue” is prepared in inserts with a porous membrane through which the nutrients pass to the cells. A cell suspension is seeded into the insert in specialized medium. After an initial period of submerged culture, the medium is removed from the top of the tissue so that the epithelial surface is in direct contact with the air. This allows the test material to be directly applied to the epithelial surface in a fashion similar to how the corneal epithelium would be exposed in vivo.
- Vehicle:
- unchanged (no vehicle)
- Controls:
- yes
- yes, concurrent positive control
- yes, concurrent negative control
- Amount / concentration applied:
- The solid test item (52.7 to 54.0 mg) was applied directly on top of the skin tissue.
LEE011-A4 was spread to match the size of the tissue. - Duration of treatment / exposure:
- 6 hours ± 15 minutes at 37.0 ± 1.0°C
- Duration of post- treatment incubation (in vitro):
- The tissues were incubated for 180 ± 10 minutes at 37°C.
- Number of animals or in vitro replicates:
- The test was performed on a total of 2 tissues per test item together with a negative control and positive control.
Before the assay was started the entire tissues were pre-wetted with 20 μL of Ca2+Mg2+-Free-DPBS. The tissues were incubated at standard culture conditions for 30 ± 2 minutes.
Two tissues were treated with 50 μL Milli-Q water (negative control) and 2 tissues with 50 μL Methyl Acetate (positive control) respectively. - Details on study design:
- At least 50 mg solid was added into the 6-well plates on top of the tissues. After the exposure period with LEE011-A4 (6 hours ± 15 minutes at 37.0 ± 1.0°C), the tissues were thoroughly rinsed with Ca2+Mg2+-free D-PBS (brought to room temperature) to remove residual test item.
The test item could not be removed completely. After rinsing the cell culture inserts were each dried carefully and immediately transferred to and immersed in
5 mL of previously warmed Assay Medium (room temperature) in a pre-labeled 12-well plate for a 25 ± 2 minute immersion incubation at room temperature (Post-Soak). After the Post-Soak period cell culture inserts were each dried carefully and transferred to the 6-well plate containing 1.0 mL of warm Assay Medium and were incubated for 18 hours ± 15 minutes at 37°C. - Irritation parameter:
- other: tissue viability
- Run / experiment:
- the mean tissue viability obtained after 6 hours ± 15 minutes treatment with LEE011-A4 compared to the negative control tissues
- Value:
- ca. 24.4
- Negative controls validity:
- valid
- Remarks:
- The relative mean tissue viability obtained after 6 hours ± 15 minutes treatment with LEE011-A4 compared to the negative control tissues was 24.4%.
- Positive controls validity:
- valid
- Remarks:
- The positive control had a mean cell viability after 6 hours ± 15 minutes exposure of 12.5%.
- Interpretation of results:
- Category 2 (irritating to eyes) based on GHS criteria
- Conclusions:
- In conclusion, LEE011-A4 is potentially irritant or corrosive in the EpiOcular™ test under the experimental conditions described in this report. The test item is identified as potentially requiring classification and labelling according to UN GHS (Category 2 or Category 1).
- Endpoint:
- eye irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Oct 2017 - Jan 2018
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)
- GLP compliance:
- yes
- Species:
- cattle
- Details on test animals or tissues and environmental conditions:
- Bovine eyes were used as soon as possible after slaughter.
- Vehicle:
- physiological saline
- Controls:
- yes, concurrent positive control
- yes, concurrent negative control
- Amount / concentration applied:
- No correction was made for the purity/composition of the test item.
A solubility test in physiological saline was performed based on visual assessment.
A 20% (w/v) suspension of the test item was prepared in physiological saline.
Any residual volumes were discarded. - Duration of treatment / exposure:
- Corneas were incubated in a horizontal position for 240 minutes at 32C.
- Duration of post- treatment incubation (in vitro):
- After the incubation the solutions
were removed and the epithelium was washed at least three times with MEM with phenol red
(Earle’s Minimum Essential Medium Life Technologies). Possible pH effects of the test item
on the corneas were recorded. Each cornea was inspected visually for dissimilar opacity patterns. The medium in the posterior compartment was removed and both compartments were refilled with fresh cMEM and the opacity determinations were performed. - Number of animals or in vitro replicates:
- First experiment: 9 (3 Negative control, 3 Positive control, 3 LEE011-A4)
Second experiment: 9 (3 Negative control, 3 Positive control, 3 LEE011-A4) - Details on study design:
- The test consists of topical application of LEE011-A4 on the epithelium of the bovine cornea for 4 hours. The non-surfactant solid test item was applied as a 20% suspension. After exposure the corneas were thoroughly rinsed. The opacity of the corneas was determined
directly after treatment and the permeability of the corneas was determined after a 90 minutes incubation period with sodium fluorescein. - Irritation parameter:
- cornea opacity score
- Run / experiment:
- first experiment
- Value:
- >= 1.3 - <= 2.5
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- not determinable
- Irritation parameter:
- other: permeability of the corneas
- Run / experiment:
- first experiment
- Value:
- >= 0.058 - <= 0.132
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- not determinable
- Irritation parameter:
- in vitro irritation score
- Run / experiment:
- first experiment
- Value:
- >= 2.9 - <= 4.5
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- not determinable
- Irritation parameter:
- cornea opacity score
- Run / experiment:
- second experiment
- Value:
- >= 1.8 - <= 2.3
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- not determinable
- Irritation parameter:
- in vitro irritation score
- Run / experiment:
- second experiment
- Value:
- >= 2.4 - <= 3.5
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- not determinable
- Irritation parameter:
- other: permeability of the corneas
- Run / experiment:
- second experiment
- Value:
- >= 0.038 - <= 0.093
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- not determinable
- Interpretation of results:
- other: Since both tests provided inconclusive results, no conclusion can be drawn for the eye irritation or serious eye damage of LEE011-A4.
- Conclusions:
- The negative control responses for opacity and permeability were less than the upper limits of the laboratory historical range indicating that the negative control did not induce irritancy on the corneas. The mean in vitro irritancy score of the positive control (20% (w/v) Imidazole)
was 162 and 158 in the first and second experiment, respectively and within two standard deviations of the current historical positive control mean. It was therefore concluded that the test conditions were adequate and that the test system functioned properly.
The mean in vitro irritancy score was 3.4 and 3.1 after 240 minutes of treatment with the test item in the first and second experiment, respectively. The results for LEE011-A4 were spread over 2 categories in both experiments.
Since both tests provided inconclusive results, no conclusion can be drawn for the eye irritation or serious eye damage of LEE011-A4.
Referenceopen allclose all
Eye hazard potential is expressed as the remaining cell viability after exposure to the test item. The relative mean tissue viability obtained after 6 hours ± 15 minutes treatment with LEE011-A4 compared to the negative control tissues was 24.4%. Since the mean relative tissue viability for LEE011-A4 was below 60% it is considered to be potentially irritant or corrosive to the eye.
The positive control had a mean cell viability after 6 hours ± 15 minutes exposure of 12.5%. The absolute mean OD570 of the negative control tissues was within the laboratory historical control data range. The difference between the percentage of viability of two tissues treated identically was less than 15%, indicating that the test system functioned properly.
In the first experiment, the individual in vitro irritancy scores for the negative controls ranged from -1.2 to 0.8. The individual positive control in vitro irritancy scores ranged from 156 to 170. The corneas treated with the positive control were turbid after the 240 minutes of treatment.
The corneas treated with LEE011-A4 showed opacity values ranging from 1.3 to 2.5 and permeability values ranging from 0.058 to 0.132. The corneas were clear after the 240 minutes of treatment with LEE011-A4. No pH effect of the test item was observed on the rinsing medium. Hence, the in vitro irritancy scores ranged from 2.9 to 4.5 after
240 minutes of treatment with LEE011-A4.
Since the results for LEE011-A4 were spread over 2 categories (2.9, 2.9 and 4.5, respectively), the test was inconclusive and a repeat experiment was performed.
In the second test, the individual in vitro irritancy scores for the negative controls ranged from -0.7 to 1.4. The individual positive control in vitro irritancy scores ranged from 142 to 184. The corneas treated with the positive control were turbid after the 240 minutes of treatment.
The corneas treated with LEE011-A4 showed opacity values ranging from 1.8 to 2.3 and permeability values ranging from 0.038 to 0.093. The corneas were clear after the 240 minutes of treatment with LEE011-A4. No pH effect of the test item was observed on the rinsing medium. Hence, the in vitro irritancy scores ranged from 2.4 to 3.5 after
240 minutes of treatment with LEE011-A4.
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irritating)
Additional information
Justification for classification or non-classification
Skin irritation/corrosion study showed that the substance has non-irritating effect.
The relative mean tissue viability obtained after 6 hours ± 15 minutes treatment with LEE011-A4 compared to the negative control tissues was 24.4%. Since the mean relative tissue viability for LEE011-A4 was below 60% it is considered to be potentially irritant or corrosive to the eye.
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.