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EC number: - | 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:
- 13 Aug 2014
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP-Guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Report date:
- 2014
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)
- Version / remarks:
- 2013
- Deviations:
- yes
- Remarks:
- a photometer instead of a opacitometer was used.
- Qualifier:
- according to guideline
- Guideline:
- EU method B.47 (Bovine corneal opacity and permeability test method for identifying ocular corrosives and severe irritants)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Landesamt für Umwelt, Wasserwirtschaft und Gewerbeaufsicht, Mainz, Germany
Test material
- Details on test material:
- - Name of test material (as cited in study report): trade name given
- Substance type: white, crystalline powder
- Analytical purity: 99.5%
- Solubility: water: < 0.1 g/L
- Lot/batch No.: 1592ZG-076
- Expiration date of the lot/batch: Aug 2015
- Storage condition of test material: at room temperature 20 ± 5 °C
Constituent 1
Test animals / tissue source
- Species:
- other: cattle
- Strain:
- other: Bos primigenius Taurus
- Details on test animals or tissues and environmental conditions:
- TEST METHOD
The bovine corneal opacity and permeability (BCOP) test method is an organotypic model that provides short-term maintenance of normal physiological and biochemical function of the bovine cornea in vitro. In this test method, damage by the test item is assessed by quantitative measurements of changes in corneal opacity and permeability. Both measurements are used to calculate an IVIS, which is used to classify the test item in the UN GHS System.
IDENTIFICATION OF THE SOURCE OF THE EYES, STORAGE AND TRANSPORT CONDITIONS
- Source: Müller Fleisch GmbH, Birkenfeld, Germany
- Donor animals: The cattle were between 12 and 60 months old.
- Transport medium and temperature conditions: Hanks´ Balanced Salt Solution (HBSS) on ice with 0.01% penicillin/streptomycin
PREPARATION OF THE EYES (BEFORE EXPOSURE)
- Eyes free of defects (scratches, neovascularisation): yes
- Dissection of the eyes and treatment: The corneas were excised with a scalpel and cut from the globe with a 2-3 mm ring of sclera around the outside. Each cornea was transferred to a cornea holder in which pre-warmed cMEM without phenol red was filled.
- Test medium and temperature conditions used in the cornea holder: Minimum Essential Medium (MEM) with and without phenol red; cMEM without phenol red supplemented with fetal calf serum, L-Glutamine and NaHCO3; cMEM with phenol red supplemented with fetal calf serum and L-Glutamine; prior to use: pre-warmed to 32±1 °C
- Equilibration time: 1 h at 32±1 °C
- Quality check of the equilibrated corneas: Yes; baseline opacity for each cornea was recorded. None of the corneas showed tissue damage. Please refer to Table 1 and 2.
DETERMINATION OF THE INITIAL OPACITY
- Method: Corneal opacity was determined by placing the holder with the cornea in a spectral photometer and recording the absorption at 570 nm. Opacity is calculated from the measured opacity following the equation:
Opacity = 10^A
A: Absorption at 570 nm
- Specification of the device: Spectral photometer, Specord 205, Analytik Jena, Germany
Test system
- Vehicle:
- unchanged (no vehicle)
- Controls:
- other: number of eyes for the negative control: 3; number of eyes for the positive control: 3
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied: 506 mg (mean)
POSITIVE SUBSTANCE
- Concentration: 20% imidazole solution in physiol. saline
- Amount(s) applied in the test: 750 µL
NEGATIVE CONTROL
- Physiological sodium chloride solution - Duration of treatment / exposure:
- 4 h ± 5 min at 32 °C
- Observation period (in vivo):
- Not applicable
- Number of animals or in vitro replicates:
- number of eyes for the test item: 3
- Details on study design:
- TEST CONDITIONS
- Short description of the method used: Open-Chamber method: In order to apply the test item, the nut was unscrewed to remove the glass disc. The controls or test substance were applied directly to the epithelial surface of the cornea. Corneas were exposed for 4 h ± 5 min with the test substance or the controls.
POST-EXPOSURE TREATMENT
- Removal of the test substance: The test substance was removed by thorough rinsing.
- Medium for washing the corneas: cMEM containing phenol red
- Medium for final rinsing: cEMEM without phenol red
DETERMINATION OF THE FINAL OPACITY
- Method: Corneal opacity was determined by measurement of the absorption at 570 nm in a spectral photometer and subsequent calculation using the following equation:
Opacity = 10^A
- Time of determination: directly after refilling fresh cMEM without phenol red in both chambers
- Specification of the device: Spectral photometer, Specord 205, Analytik Jena, Germany
DETERMINATION OF THE CORNEAL PERMEABILITY:
- Method: Sodium fluorescein solution was added to the front chamber of the cornea holder. The amount of sodium fluorescein that crosses into the posterior chamber was quantitatively measured via UV/VIS spectrophotometry at 490 nm recorded as optical density (OD490).
- Amount and concentration of the dye: 1 mL sodium fluorescein solution (5 mg/mL)
- Incubation time: 90 ± 5 min at 32 ± 1 °C
- Treatment for measuring: OD490 of an aliquot was determined in a cuvette with a path length of 0.2 cm.
- Specification of the spectrophotometer: Spectral photometer, Specord 205, Analytik Jena, Germany
Results and discussion
In vivo
Resultsopen allclose all
- Irritation parameter:
- other: opacity
- Basis:
- other: mean out of all 3 eyes
- Time point:
- other: 4 h
- Score:
- 0.285
- Reversibility:
- other: not applicable
- Remarks on result:
- other: Test substance
- Irritation parameter:
- other: permeability
- Basis:
- other: mean out of all 3 eyes
- Time point:
- other: 4 h
- Score:
- 0.031
- Reversibility:
- other: not applicable
- Remarks on result:
- other: Test substance
- Irritation parameter:
- other: IVIS
- Basis:
- other: mean out of all 3 eyes
- Time point:
- other: 4 h
- Score:
- -0.585
- Reversibility:
- other: not applicable
- Remarks on result:
- other: Test substance
- Irritation parameter:
- other: opacity
- Basis:
- other: mean out of all 3 eyes
- Time point:
- other: 4 h
- Score:
- 101.116
- Reversibility:
- other: not applicable
- Remarks on result:
- other: Positive control
- Irritation parameter:
- other: permeability
- Basis:
- other: mean out of all 3 eyes
- Time point:
- other: 4 h
- Score:
- 1.247
- Reversibility:
- other: not applicable
- Remarks on result:
- other: Positive control
- Irritation parameter:
- other: IVIS
- Basis:
- other: mean out of all 3 eyes
- Time point:
- other: 4 h
- Score:
- 118.485
- Reversibility:
- other: not applicable
- Remarks on result:
- other: Positive control
- Irritation parameter:
- other: opacity
- Basis:
- other: mean out of all 3 eyes
- Time point:
- other: 4 h
- Score:
- 0.388
- Reversibility:
- other: not applicable
- Remarks on result:
- other: Negative control
- Irritation parameter:
- other: permeability
- Basis:
- other: mean out of all 3 eyes
- Time point:
- other: 4 h
- Score:
- 0.063
- Reversibility:
- other: not applicable
- Remarks on result:
- other: Negative control
- Irritation parameter:
- other: IVIS
- Basis:
- other: mean out of all 3 eyes
- Time point:
- other: 4 h
- Score:
- 1.333
- Reversibility:
- other: not applicable
- Remarks on result:
- other: Negative control
- Irritant / corrosive response data:
- The negative control (physiological sodium chloride solution) showed no irritating effect on the cornea.
The positive control (20% imidazole solution) induced serious eye damage on the cornea.
Under the conditions of the test system, the test substance showed no effects on the cornea of the bovine eye. The calculated In Vitro Irritancy Score (IVIS) is -0.585.
Any other information on results incl. tables
Table 1. Absorption and opacity values negative control.
Parameter |
Negative control |
||
Absorption before exposition |
0.1636 |
0.1674 |
0.1628 |
Absorption after exposition |
0.2477 |
0.2092 |
0.3342 |
Opacity before exposition |
1.4575 |
1.4703 |
1.4548 |
Opacity after exposition |
1.7689 |
1.6188 |
2.1587 |
Opacity Difference |
0.3114 |
0.1485 |
0.7039 |
Table 2. Absorption and opacity values test substance and positive control.
Parameter |
Test substance |
Positive control |
||||
Absorption before exposition |
0.1402 |
0.2017 |
0.1976 |
0.1309 |
0.168 |
0.1629 |
Absorption after exposition |
0.2621 |
0.2345 |
0.2696 |
2.1271 |
1.8589 |
2.0059 |
Opacity before exposition |
1.3810 |
1.5911 |
1.5762 |
1.3518 |
1.4723 |
1.4551 |
Opacity after exposition |
1.8285 |
1.7159 |
1.8604 |
133.9985 |
72.2603 |
101.3678 |
Opacity Difference |
0.4475 |
0.1248 |
0.2842 |
132.6468 |
70.7880 |
99.9127 |
Table 3. Optical density at 490 nm.
Repl. |
Negative control |
Test substance |
Positive control |
||||||
Meas. |
0.0083 |
0.0151 |
0.0144 |
0.0070 |
0.0052 |
0.0063 |
0.2220 |
0.2637 |
0.2624 |
Corr. |
0.0415 |
0.0755 |
0.0720 |
0.0350 |
0.0260 |
0.0315 |
1.1100 |
1.3185 |
1.3120 |
Mean |
0.0630 |
0.0308 |
1.2468 |
Table 4. IVIS
Test group |
IVIS |
Mean IVIS |
Relative standard deviation IVIS |
Negative control 0.9% NaCl |
0.934 |
1.333 |
32.1% |
1.281 |
|||
1.784 |
|||
Test substance |
- 0.360 |
-0.585 |
39.1% |
- 0.818 |
|||
- 0.576 |
|||
Positive control |
147.964 |
118.485 |
24.8% |
89.233 |
|||
118.260 |
Table 5. Validity
Parameter |
Criterion |
Found |
Assessment |
IVIS of negative control 0.9% NaCl |
0 -3 |
1.333 |
ok |
IVIS of positive control 20% imidazole |
35.6 – 129.2 |
118.458 |
ok |
Table 6. Historical data (all experiments up to 13 May 2014).
Parameter |
IVIS negative control |
IVIS positive control |
Substance |
0.9% sodium chloride solution |
20% imidazole solution |
Mean |
1.064 |
82.4 |
Standard Deviation |
0.488 |
23.4 |
Range (min – max) |
0.138 - 2.281 |
32.6 - 132.4 |
Range (validity) |
0 -3 |
35.6 – 129.2 |
Study 14071601G850 |
1.333 |
118.458 |
All three values for negative and two values for positive controls were within the range of historical data of the test facility. Therefore, the test system was acceptable.
Applicant's summary and conclusion
- Interpretation of results:
- not irritating
- Remarks:
- Migrated information Criteria used for interpretation of results: EU
- Conclusions:
- CLP: not classified
DSD: not classified
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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