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EC number: 946-442-6 | 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
Eye irritation
Administrative data
- Endpoint:
- eye irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 30 August - 21 September 2017
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Remarks:
- GLP study performed according to OECD Guideline 492 without any deviation
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 017
- Report date:
- 2017
Materials and methods
Test guideline
- 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)
- Version / remarks:
- adopted 28 July 2015
- Deviations:
- no
- Principles of method if other than guideline:
- Not applicable
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- 27 April 2017
Test material
- Reference substance name:
- Resinoid of Cistus ladaniferus (Cistaceae) obtained from labdanum gum by organic solvents extraction
- EC Number:
- 946-442-6
- Molecular formula:
- Not applicable
- IUPAC Name:
- Resinoid of Cistus ladaniferus (Cistaceae) obtained from labdanum gum by organic solvents extraction
- Test material form:
- solid
- Remarks:
- brown to brown-red paste
- Details on test material:
- - Name (as cited in study report): LABDANUM RESINOID / F
- Storage condition of test material: room temperature, darkness, closed container
Constituent 1
Test animals / tissue source
- Species:
- human
- Details on test animals or tissues and environmental conditions:
- - Justification of the test method and considerations regarding applicability: the OECD 492 (adopted in 2015), is validated and has regulatory acceptance. This test guideline is applicable to solid and waxes, so is considered to be applicable to the test item.
RECONSTRUCTED HUMAN CORNEA-LIKE EPITHELIUM (RhCE)
- Model used: EpiOcularTM OCL-212-ver2.0, supplied by MatTek Corporation
- Tissue batch number(s): 27005
- Keratinocyte strain: 4F1188
FUNCTIONAL MODEL CONDITIONS
- Tissue viability: 1.419, within the acceptance criteria (1.1-3.0)
- Barrier function: 15.97 min, within the acceptance criteria (12.2-37.5)
- Sterility: Sterile
Test system
- Vehicle:
- unchanged (no vehicle)
- Controls:
- yes, concurrent positive control
- yes, concurrent negative control
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 50 mg
- Concentration (if solution): undiluted
NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 50 µL
- Concentration (if solution): undiluted
POSITIVE CONTROL
- Amount(s) applied (volume or weight): 50 µL
- Concentration (if solution): undiluted - Duration of treatment / exposure:
- 6 hours at 37°C, 5% CO2, 95% humidity (standard culture conditions)
- Duration of post- treatment incubation (in vitro):
- - Post-exposure immersion period: 25 minutes at room temperature
- Post-exposure incubation period: 18 hours at standard culture conditions - Number of animals or in vitro replicates:
- 2
- Details on study design:
- - Details of the test procedure used: method for solids (not pipetteable), as described in the OECD TG 492
- RhCE tissue construct used, including batch number: EpiOcularTM OCL-212-ver2.0, supplied by MatTek Corporation, batch No. 27005
- Doses of test chemical and control substances used: 50 mg / 50 µL
- Duration and temperature of:
Exposure: 6 hours at 37°C, 5% CO2, 95% humidity (standard culture conditions)
Post-exposure immersion: 25 minutes at room temperature
Post-exposure incubation periods: 18 hours at standard culture conditions
- Description of any modifications to the test procedure: None
- Indication of controls used for direct MTT-reducers and/or colouring test chemicals (if applicable): not applicable.
- Number of tissue replicates used per test chemical and controls (positive control, negative control): 2
- Wavelength used for quantifying MTT formazan, measuring device (e.g. spectrophotometer): 570 nm, ELx800 absorbance microplate reader (controlled every year and calibrated if necessary) supplied by BioTek and the validated software Gen5 ELISA V1.05.11 supplied by BioTek.
- Description of the method used to quantify MTT formazan
The RhCE constructs were placed in 300 µL of a MTT solution at 1.0 mg/mL for 2 hours and 52 minutes at standard culture conditions.
The precipitated blue formazan product was then extracted from the tissues by placing each insert in 2 mL of isopropanol during 2 hours at 6±3°C in the dark.
The concentration of formazan was measured by determining the OD (Optical Density) at 570 nm, just after dilution of the extractions in isopropanol (1:2).
The OD at 570 nm was measured in triplicate samples of formazan extracts.
The measured OD are proportional to the number of living cells.
- Description of evaluation criteria used including the justification for the selection of the cut-off point for the prediction model
The test substance is considered to be corrosive or irritant to eyes if the mean percent tissue viability after exposure and post-exposure incubation is ≤ 60%. When the final mean percent tissue viability is ≤ 60%, further testing with other test methods will be required because the RhCE test method shows a certain number of false positive results and cannot resolve between UN GHS Categories 1 and 2.
The test substance is considered to be non-irritant to eyes if the mean percent tissue viability after exposure and post-exposure incubation is > 60%.
- Complete supporting information for the specific RhCE tissue construct used
- Demonstration of proficiency in performing the test method before routine use by testing of the proficiency chemicals: included in the report, follows the OECD TG 492.
Results and discussion
In vitro
Results
- Irritation parameter:
- other: % mean viability of the tissues
- Run / experiment:
- 1
- Value:
- 17.62
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks:
- 14.96 %
- Remarks on result:
- positive indication of irritation
- Other effects / acceptance of results:
- MAIN TEST
- MTT assay results - Second run: The mean percent tissue viability of the RhCE replicates treated with the test substance was 17.62 versus 14.96% in the positive control (Methyl acetate).
OTHER EFFECTS:
- Visible damage on test system: none
ACCEPTANCE OF RESULTS:
FIRST RUN
During the first run, the percentage of viability of 1/2 epidermis of the positive control (Methyl acetate) was higher than 50%. It was not possible to conclude for the test item because the acceptability criteria defined in OECD 439 was not respected. A second run was necessary.
SECOND RUN:
- Acceptance criteria met for negative control: yes, the negative control OD is > 0.4 and < 1.25 (values between 0.528 and 0.700).
- Acceptance criteria met for positive control: yes, the mean relative viability of the positive control is below 50% of the negative control viability (14.96%).
- Acceptance criteria met for variability between replicate measurements: yes, the difference of viability between the two relating tissues of the test item and the positive control are < 20% (0.00% and 2.66%, respectively). The difference of viability between the two relating tissues is slightly above the threshold of 20% for the negative control (21.11%). However, this deviation is not considered to have affected the integrity of the study or the overall conclusion.
The quality criteria required for acceptance of results in the test were satisfied.
- Range of historical values if different from the ones specified in the test guideline: The positive and negative control OD were within the historical control ranges
Any other information on results incl. tables
Table 7.3.2/1: Second run - Individual and mean corrected OD values and tissue viabilities for the test item, the negative and positive controls
Tissue |
OD |
Mean OD/disc (#) |
Mean OD/product |
Viability % |
Mean viability % |
Difference of viability % |
|
Negative control |
1 |
0.700 |
0.665 |
0.602 |
110.56 |
100.00 |
21.11 |
0.640 |
|||||||
0.657 |
|||||||
2 |
0.550 |
0.538 |
89.44 |
||||
0.537 |
|||||||
0.528 |
|||||||
Positive control |
1 |
0.111 |
0.098 |
0.090 |
16.29 |
14.96 |
2.66 |
0.094 |
|||||||
0.091 |
|||||||
2 |
0.076 |
0.082 |
13.63 |
||||
0.087 |
|||||||
0.085 |
|||||||
Test item |
1 |
0.104 |
0.106 |
0.106 |
17.62 |
17.62 |
0.00 |
0.107 |
|||||||
0.107 |
|||||||
2 |
0.108 |
0.106 |
17.62 |
||||
0.110 |
|||||||
0.101 |
#: mean of 3 values (triplicate of the same extract)
OD: optical density
Applicant's summary and conclusion
- Interpretation of results:
- other: Category 1 (irreversible effects on the eye) or Category 2 (irritating to eyes) based on GHS criteria
- Conclusions:
- With a percentage of tissue viability < 60%, the test item requires classification as irritating or corrosive to eyes according to the Regulation (EC) No 1272/2008 (CLP) and to the GHS.
- Executive summary:
An in vitro eye irritation test using the Reconstructed human Cornea-like Epithelium (RhCE) (EpiOcular™ tissue) model was performed according to the OECD Guideline 492 and in compliance with GLP to predict the acute eye irritation potential of the test substance.
The test item was applied, to 2 DPBS pre-treated RhCE (EpiOcularTM tissue model) during 6 hours at 37°C, 5% CO2, 95% humidity (standard culture conditions). The exposure period was followed by extensive rinsing with DPBS at room temperature, a 25 minutes post-exposure immersion period at room temperature and an 18 hours post-exposure incubation at standard culture conditions. The tissue viability was measured by performing an MTT assay. The experimental protocol was established in accordance with O.E.C.D. Test Guideline No. 492 adopted 28 July 2015.
During the first run, the percentage of viability of 1/2 epidermis of the positive control (Methyl acetate) was higher than 50%. It was not possible to conclude for the test item because the acceptability criteria define in OECD 439 was not respected. A second run was necessary.
In the second run, the mean percent tissue viability of the RhCE replicates treated with the test item was 17.62%, versus 14.96% in the positive control (Methyl acetate).
In the second run, the quality criteria required for acceptance of results in the test were satisfied.
- Acceptance criteria met for negative control: yes, the negative control OD is > 0.4 and < 1.25 (values between 0.528 and 0.700).
- Acceptance criteria met for positive control: yes, the mean relative viability of the positive control is below 50% of the negative control viability (14.96%).
- Acceptance criteria met for variability between replicate measurements: yes, the difference of viability between the two relating tissues of the test item and the positive control are < 20% (0.00% and 2.66%, respectively). The difference of viability between the two relating tissues is slightly above the threshold of 20% for the negative control (21.11%). However, this deviation is not considered to have affected the integrity of the study or the overall conclusion.
The positive and negative control OD were within the historical control ranges.
With a percentage of tissue viability < 60%, the test item requires classification as irritating or corrosive to eyes according to the Regulation (EC) No 1272/2008 (CLP) and to the GHS.
This study is considered as acceptable and satisfies the requirement for eye irritation endpoint.
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