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EC number: 262-765-9 | CAS number: 61397-56-6
- 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
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- 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
Skin irritation:
In a K1 in vivo skin irritation study in New Zealand White rabbits according to OECD Guideline 404 and EU Method B.4, T001095 was observed to be non-irritating to the skin.
Eye irritation:
In a K1 Bovine Corneal Opacity and Permeability (BCOP) test, performed according according to INVITTOX protocol no. 98 "Bovine Corneal Opacity and Permeability Assay" and Bovine Corneal Opacity and Permeability Assay (BCO -P) SOP of Microbiological Associates Ltd., UK, and similar to Draft OECD guideline 437 "The Bovine Corneal Opacity and Permeability (BCOP) Test Method for Identifying Ocular Corrosives and Severe Irritants", T001095 was not considered to be an eye irritant.
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:
- 2006-05-24 to 2006-06-01
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Remarks:
- Comparable to OECD Guideline 404 and EU Guildine B.4 study with acceptable restrictions.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Deviations:
- yes
- Remarks:
- : 1) the test substance was put on a surgical gauze patch of approximately 4 cm x 4 cm (instead of 6 cm2) to guarantee a good contact and uniform distribution of the test substance on the skin
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
- Deviations:
- yes
- Remarks:
- : 1) the test substance was put on a surgical gauze patch of approximately 4 cm x 4 cm (instead of 6 cm2) to guarantee a good contact and uniform distribution of the test substance on the skin
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Certificate from the Swiss GLP Monitoring Authorities
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Harlan Netherlands BV, Kreuzelweg 53, NL-5961 NM Horst / The Netherlands
- Age at study initiation: 12-13 weeks (male); 8-9 weeks (female)
- Weight at study initiation: 2463 g (male); 1726 and 2021 g (females)
- Housing: Housed in a wire cage in compliance with AALAC regulations. Animals were housed ndividually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks (RCC Ltd., Fullinsdorf) and haysticks 4642 (batch no. 77/05, Provimi Kliba AG) were provided for gnawing.
- Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 8/06) provided by Provimi Kliba AG, CH-4303 Kaiseraugst. Results of analysis for contaminants are archived at RCC Ltd.
- Water: Community tap water from Fullinsdorf, ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at RCC Ltd.
- Acclimation period: From 2006-05-24 to 2006-05-28 under laboratory conditions after health examination.
ENVIRONMENTAL CONDITIONS
- Temperature (deg C): 17-23 deg C, monitored continuously and values outside of the range may have occasionally occurred, usually following room cleaning. These transient variations are considered not to have any influence on the study.
- Humidity (%): air conditioned with relative humidity between 30-70% monitored continuously and values outside of the range may have occasionally occurred, usually following room cleaning. These transient variations are considered not to have any influence on the study.
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 hrs light and 12 hrs dark
IN-LIFE DATES: From: 2006-05-24 To: 2006-06-01 - Type of coverage:
- semiocclusive
- Preparation of test site:
- shaved
- Vehicle:
- unchanged (no vehicle)
- Controls:
- not specified
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g moistened with 0.5 mL purified water
- Concentration (if solution): no data
VEHICLE
- Amount(s) applied (volume or weight with unit): not applicable - Duration of treatment / exposure:
- 4 hours
- Observation period:
- 1, 24, 48 and 72 hours after exposure
- Number of animals:
- 3 (1 male and 2 females)
- Details on study design:
- TEST SITE
- Area of exposure: The left flank was clipped with an electric clipper, exposing an area of approximately 100 cm2 (10 cm x 10 cm). The test substance was applied with a 4 cm x 4 cm surgical gauze patch
- % coverage: no data
- Type of wrap if used: The test substance was applied with a 4 cm x 4 cm surgical gauze patch. The gauze patch was applied to the intact skin of the clipped area. The patch was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with tape.
REMOVAL OF TEST SUBSTANCE
- Washing (if done): flushed with lukewarm tap water
- Time after start of exposure: 4 hours
SCORING SYSTEM:
- The skin reaction was assessed according to the numerical scoring system listed in the Commission Directive 2004/73/EC, April 29, 2004.
If evident, corrosive or staining properties of the test substance were described and recorded.
Commission Directive 2004/73/EC, April 29, 2004, Grading of Skin Reactions
Erythema and Eschar Formation:
No erythema =0
Very slight erythema = 1
Well-defined erythema = 2
Moderate to severe erythema = 3
Severe erythema (beef redness) or eschar formation (injuries in depth preventing erythema) reading = 4
Oedema Formation:
No oedema = 0
Very slight oedema (barely perceptible) = 1
Slight oedema (edges of area well-defined by definite raising) = 2
Moderate oedema (edges raised approximately 1 mm) = 3
Severe oedema (raised more than 1 mm and extending beyond the area of exposure) = 4 - Irritation parameter:
- erythema score
- Basis:
- animal: 16
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: Not applicable
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- edema score
- Basis:
- animal: 16
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: Not applicable
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- erythema score
- Basis:
- animal: 17
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: Not applicaable
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- edema score
- Basis:
- animal: 17
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: Not applicable
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- erythema score
- Basis:
- animal: 18
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: Not applicable
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- edema score
- Basis:
- animal: 18
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 4
- Reversibility:
- other: Not applicable
- Remarks on result:
- no indication of irritation
- Irritant / corrosive response data:
- The test substance did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0). The individual mean score for erythema/eschar and oedema for each of the three animals was therefore 0.
Neither alterations of the treated skin were observed, nor were corrosive effects evident on the skin. - Other effects:
- No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.
No staining produced by the test substance of the treated skin was observed.
The body weights of all rabbits were considered to be within the normal range of variability. - Interpretation of results:
- GHS criteria not met
- Conclusions:
- Based upon the referred classification criteria (Commission Directive 2001/59/EC of August 2001), the test substance is considered to be "not irritating" to rabbit skin, and therefore should not be classified.
- Endpoint:
- skin corrosion: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- 2006-02-09 to 2006-02-10
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- Well documented non-GLP study performed according to OECD Guideline for testing of Chemicals, Draft OECD Guideline 430, In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test (TER), 27 March 2002.
- Qualifier:
- according to guideline
- Guideline:
- other: Draft OECD Guideline 430, In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test (TER), 27 March 2002
- Deviations:
- no
- GLP compliance:
- not specified
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 00452023 ZT001095PUA121
- Expiration date of the lot/batch:Not indicated by the Sponsor
- Purity test date: Not indicated by the Sponsor
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature, protected from moisture
- Stability under test conditions:
- Solubility and stability of the test substance in the solvent/vehicle: solubility: < 0.05 g/L in water, 37 g/L in acetone, 1.9 g/L in ethanol
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: - Test system:
- isolated skin discs
- Source species:
- rat
- Source strain:
- Wistar
- Details on animal used as source of test system:
- TEST ANIMALS: epidermal surface of skin discs.
- According to the supplier's assurance the animals were in healthy condition. The animals underwent quarantine in the animal house of RCC - CCR for 6 days after their arrival. During this period the animals did not show signs of illness or altered behaviour.
- Source: Harlan Winkelmann GmbH, D-33178 Borchen
- Sex: no data
- Age at study initiation (in days): 29 days old
- Weight at study initiation: no data
- Housing: Single, Makrolon Type II, with wire mesh top (EHRET GmbH, D-79302 Emmendingen (EHRET GmbH, D-79302 Emmendingen. Granulated soft wood bedding (Harlan Winkelmann GmbH, D-33178 Borchen) .
- Diet (e.g. ad libitum): pelleted standard diet, ad libitum (Harlan Winkelmann GmbH, D-33178 Borchen)
- Water (e.g. ad libitum): tap water, ad libitum, (Gemeindewerke, D-64380 Rossdorf)
- Acclimation period: minimum of 6 days
ENVIRONMENTAL CONDITIONS
- Temperature (deg C): 21 +/- 3 deg C
- Humidity (%): 30 - 70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hrs light, 12 hrs dark - Vehicle:
- not specified
- Details on test system:
- SKIN DISC PREPARATION
- Procedure used: Animals were anaesthetised with CO2 and subsequently decapitated. The dorsal skin of each animal was removed and stripped of excess fat by carefully peeling it away from the skin. The skin was placed over the end of a PTFE (polytetrafluoroethylene) tube, ensuring that the epidermal surface was in contact with the tube. A rubber ‘O’ ring was press-fitted over the end of the tube to hold the skin in place and excess tissue was trimmed away. Tube and ‘O’ ring dimensions are shown in annex 1. The tube was supported by a spring clip inside a receptor chamber containing magnesium sulphate solution (154 mM)
TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: room temperature
REMOVAL OF TEST MATERIAL AND CONTROLS
- Washing (if done): yes, removed using a jet of warm tap water up to 30 °C until no further material could be removed
-Time after start of exposure: after 24 hour exposure
NUMBER OF INDEPENDENT TESTING RUNS / EXPERIMENTS TO DERIVE FINAL PREDICTION: 1
PREDICTION MODEL / DECISION CRITERIA
- The test substance is considered to be corrosive to skin if [complete, e.g. if the mean TER value is less than or equal to 5 kΩ and the skin disk is obviously damaged, or if the mean TER value is less than or equal to 5 kΩ, and the skin disc is showing no obvious damage, but the mean disc dye content is greater than or equal to the mean disc dye content of the 10M HCl positive control obtained concurrently.]
- The test substance is considered to be non-corrosive to skin if [complete, e.g. if the mean TER value obtained for the test substance is greater than 5 kΩ, or if the mean TER value is less than or equal to 5 kΩ, and the skin disc is showing no obvious damage, and the mean disc dye content is well below the mean disc dye content of the 10M HCl positive control obtained concurrently.]
- Justification for the selection of the cut-off point(s) if different than recommended in TG 430: - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1686 g, 0.1514 g, or 0.1588 g. 150 uL deionised water was added on top of the test substance and evenly distributed by shaking of the tube.
- Concentration (if solution): not applicable
NEGATIVE CONTROL
- Amount(s) applied (volume or weight with unit): 150 µL
POSITIVE CONTROL
- Amount(s) applied (volume or weight with unit): 150 µL
- Concentration (if solution): 36% ~10 M - Duration of treatment / exposure:
- 24 hours
- Number of replicates:
- 3 skin discs per test group
- Irritation / corrosion parameter:
- transcutaneous electrical resistance (in kΩ)
- Run / experiment:
- mean
- Value:
- 15.59
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other:
- Remarks:
- Basis: mean. Time point: after 24 hours. Remarks: standard deviation = 6.64.
- Other effects / acceptance of results:
- The mean electrical resistance (kΩ) was 15.59 +/- 6.64. Following visual inspection, each skin disc was macroscopically intact after treatment.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- It can be stated that the test substance did not corrode rat skin under the experimental conditions used. Both positive and negative control reached typical impedance values as stated in the guideline and in the range of historical controls.
Therefore, the test substance is considered to be non-corrosive in this TER test.
Referenceopen allclose all
Table 1.Summary of TER-Results
Sample |
Resistance (kOhm) |
Mean |
Standard Deviation |
Corrosive |
Negative Control 1 |
11.36 |
13.08 |
4.67 |
no |
Negative Control 2 |
10.64 |
|||
Negative Control 3 |
17.24 |
|||
Positive Control 1 |
0.83 |
0.76 |
0.07 |
yes |
Positive Control 2 |
0.75 |
|||
Positive Control 3 |
0.69 |
|||
Test Substance 1 |
11.87 |
15.59 |
6.64 |
no |
Test Substance 2 |
23.26 |
|||
Test Substance 3 |
11.63 |
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:
- 2005-10-27 to 2005-10-28
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study
- Remarks:
- Study was conducted according to INVITTOX protocol no. 98 "Bovine Corneal Opacity and Permeability Assay" and Bovine Corneal Opacity and Permeability Assay (BCO-P) SOP of Microbiological Associates Ltd., UK, and similar to Draft OECD guideline 437 "The Bovine Corneal Opacity and Permeability (BCOP) Test Method for Identifying Ocular Corrosives and Severe Irritants". Dec 18, 2008 with the following acceptable deviation: no data was provided on the purity of the test substance.
- Qualifier:
- according to guideline
- Guideline:
- other: INVITTOX (UK) protocol no. 98 "The Bovine Corneal Opacity and Permeability Assay", dated February 1994
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: Bovine Corneal Opacity and Permeability (BCOP) Assay, SOP of Microbiological Associates Ltd., UK, Procedure Details, April 1997
- Deviations:
- no
- GLP compliance:
- not specified
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 00452023 ZT001095PUA121
- Expiration date of the lot/batch: no data
- Purity test date: no data
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature (range of 20 +/- 5 deg C), light protected
- Stability under test conditions: no data
- Solubility and stability of the test substance in the solvent/vehicle: test substance was tested at a concentration of 20% in saline. Strong stirring with a magnetic stirrer resulted in suspension.
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: no data - Species:
- other: bovine corneas
- Strain:
- other:
- Remarks:
- not applicable
- Details on test animals or tissues and environmental conditions:
- Test system: freshly isolated bovine cornea
Source:. Abattoir Basel, Schlachthofstrasse 55, CH-4055 Basel, Switzerland.
Collection of bovine eyes:
Freshly isolated bovine eyes were collected from the abattoir. After excess tissue was removed from the excised eyes, they were stored at room temperature in Hank's balanced salt solution containing penicillin / streptomycin and then transported for further preparations. The eyes were delivered the day before treatment and the isolated corneas were stored overnight in a preservation medium (Medium 199 supplemented with L-glutamine, Na-biocarbonate and Taurine) in a refrigerator.
Preparation of corneas: All eyes were carefully examined macroscopically for defects. Those presenting defects such as vascularization, pigmentation, opacity, and scratches were discarded. Each cornea was dissected fr om the eye using scalpel and rounded scissors. A rim of about 2-3 mm of tissue (sclera) was left fo r stability and handling of the isolated cornea. All corneas used in the experiment were collected in complete minimum essential medium (cMEM) and were checked finally with a view box for the defect s listed above. Since the bovine eyes were delivered in the afternoon, corneas were stored in a preservation medium over night in a refrigerator at about 4°C. The preservation medium was composed of Medium 199 supplemented with L-glutamine, Na-bicarbonate and Taurine. Shortly before use, dextran was added. Each cornea was mounted in a cornea holder with the endothelial side against the sealing ring (Oring) of the posterior part of the holder. The cornea was gently flattened over the O-ring but stretching had to be avoided. After the anterior part of the holder was positioned on the top of the cornea and fixed in place with screws, both compartments of the holder were filled with cMEM. The posterior compartment had to be filled to return the cornea to its natural convex position. Care must be taken to assure no air bubbles were present within the compartments. For equilibration, the corneas in the holder were incubated for about one hour at 32°C +/- 2°C in a water-bath. At the end of the incubation period, the medium was removed from both compartments and replaced by fresh cMEM, and the basal opacity was determined (t0min). For measurement, the posterior compartment was plugged while the anterior compartment remained unplugged. - Vehicle:
- other:
- Remarks:
- physiological saline natrium chloratum 0.9%
- Controls:
- other: negative (saline) and positive (imidazole, 20% in saline)
- Amount / concentration applied:
- TEST MATERIAL
- Concentration (if solution): 20%
Until administration, the solution was stirred with a magnetic stirrer
VEHICLE
- Concentration (if solution): 0.9% sodium chloride in water
- Amount(s) applied (volume or weight with unit): 0.75 mL
- Lot/batch no. (if required): Charge No. 773609
- Purity: no data
NEGATIVE CONTROL - Amount(s) applied (volume or weight with unit): 0.75 mL
POSITIVE CONTROL - Amount(s) applied (volume or weight with unit): 0.75 mL
- Concentration (if solution): >/=99.9% (Assay) - Duration of treatment / exposure:
- 240 minutes
- Duration of post- treatment incubation (in vitro):
- After 240 ± 1 minutes of treatment, the corneas were thoroughly rinsed to remove test item and incuba ted for 120 ± 10 minutes at 32 ± 1°C with fresh medium followed by opacity measurement. The permeability measurement of the corneas was performed following the opacity measurement after an incubation period of 90 minutes ± 5 minutes.
- Number of animals or in vitro replicates:
- Three corneas were selected at random for each treatment group
- Details on study design:
- TREATMENT METHOD:
The medium from the anterior compartment was removed and 750 µL of either the negative control, positive control or test item was introduced onto the epithelium of the cornea. Corneas were incubated for 240 minutes at 32 ± 2°C.
REMOVAL OF TEST SUBSTANCE
Preparation of the test item solution: The test item was tested at a concentration of 20% in saline. Strong stirring with a magnetic stirrer resulted in a solution. Until administration, the solution was stirred with a magnetic stirrer.
REMOVAL OF TEST SUBSTANCE:
- Washing (if done): The test substance was rinsed off from the application side by changing cMEM several times until precipitates of the test substance could be observed no longer, fresh cMEM was replaced inboth compartments and opacity was measured.
- Time after start of exposure: 240 minutes
METHODS FOR MEASURED ENDPOINTS:
- OPACITY MEASUREMENT: After recording the basal opacity of all corneas, the mean value of all corneas was calcualted. No cornea deviated from this by more than +/-3 units and no cornea was discarded. Sets of three cor neas were used for treatment with the test item, the negative and positive controls, respectively. Medium was completely removed from the anterior compartment and replaced by the test item, positiv e or negative control. The anterior compartment was plugged. The holder was turned to a horizontal position and slightly rotated to ensure uniform covering of the cornea with the test item and will be incubated in a horizontal positioning a water-bath at 32°C +/- 2°C.
PERMEABILITY DETERMINATION:
-Following the opacity readings after treatment, the permeability endpoint was measured as an indicated of the integrity of the epithelial cell sheets. After the final opacity measurement was performed, the medium was removed from teh aniterior compartment and repalced by 1 mL of a fluorescein solution. Corneas were incubated again in a horizaontal position for about 90 minutes in a water-bath at 32 ± 2°C. Medium from the posterior compartment was removed with a 5 mL-syringe, well mixed and transferred to a cuvette of 10 mm path length and optical density at 490 nM (OD 490) was determined with a spectophotometer.
In vitro score calculation
The following formula was used to determine the in vitro score: in vitro score = opacity value + (15 x OD490 value)
The in vitro score was calculated for each individual treatment and positive control cornea. The in vitro score value of each treated group was calculated from the individual in vitro score values:
Negative control: in vitro score = opacity value + (15 x OD490 value)
Positive control and test item cornea: in vitro score = corrected opacity value + (15 x corrected OD490 value)
Depending on the score obtained, the test item was classified into one of the following categories:
in vitro score 0 - 3: non eye irritant
in vitro score 3.1 - 25: mild eye irritant
in vitro score 25.1 - 55: moderate eye irritant
in vitro score 55.1 - 80: severe eye irritant
in vitro score > 80.1: very severe eye irritant - Irritation parameter:
- in vitro irritation score
- Remarks:
- mean
- Run / experiment:
- Test item after 240 minutes of exposure
- Value:
- 0.5
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: SD +/- 0.6
- Irritation parameter:
- cornea opacity score
- Remarks:
- mean
- Run / experiment:
- Test item as 240 minutes of expsure
- Value:
- 0.3
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: SD +/- 0.6
- Irritation parameter:
- other: permeability value mean
- Run / experiment:
- Test item after 240 minutes
- Value:
- 0.011
- Vehicle controls validity:
- valid
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- other: SD +/- 0.007
- Other effects / acceptance of results:
- Other effects / acceptance of results
mean in vitro irritancy score (range):
negative control: 0.5 (-0.7 to 2.2)
positive control: 81.1 (70.5 to 95.1)
mean opacity scores (range):
negative control: 0.3 (-1 to 2)
positive control: 65.7 (59.7 to 71.7)
mean permeability scores (range):
negative control: 0.014 (0.011 to 0.018)
positive control: 1.029 (0.724to 1.561) - Interpretation of results:
- GHS criteria not met
- Conclusions:
- Under the given test conditions, the test substance is not considered to be an eye irritant.
Reference
Before starting the permeability test, the dye solution sodium fluorescein was checked for its quality. The dye solution is valid for use, if a dilution of the stock solution containing 10 µg/mL showed an optical density (OD490) of 1.610 to 1.910. The value found by spectroscopy was 1.697. According to the results obtained in this experiment, the test was considered acceptable.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Skin irritation / corrosion:
TalviOja (2006) investigated acute dermal irritation of T001095 in New Zealand White rabbits (1 male and 2 females after 4 hours of exposure to 0.5 g of test item). Skin reactions were recorded 1, 24, 48 and 72 hours after administration and scored according to the Draize scale. No evidence of skin irritation was noted. The test item did not meet the criteria for classification as irritant or corrosive according to the criteria of the CLP Regulation (EC) No 1272/2008.
In addition, Meurer (2006) investigated the dermal corrosion of T001095 in isolated skin discs from the Wistar rat (3 skin discs after 24 hours of exposure to 0.1686 g, 0.1514 g, or 0.1588 g of test item). The transcutaneous electrical resistance was measured. The test item did not corrode the rat skin, therefore, the test item did meet the criteria for classification as corrosive according to the criteria of the CLP Regulation (EC) No 1272/2008.
Eye irritation:
Deparade (2006) investigated eye irritation in an in vitro bovine corneal opacity-permeability (BCOP) assay. 750 μl of T001095 (20% w/v suspension in physiological saline) was applied for 240 minutes. Both opacity and permeability were measured and the resulting objective values were combined in an empirically derived formula to generate an In Vitro Irritancy Score (IVIS). A mean in vitro irritancy score of 0.5 SD +/- 0.6 was calculated after 240 minutes of treatment. Since the test item induced an IVIS ≤3 , it is concluded that T001095 is a not an eye irritant in the Bovine Corneal Opacity and Permeability test under the experimental conditions described in the report and should not be classified as an eye irritant according to the Globally Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations.
Justification for classification or non-classification
Skin irritation:
According to the in vivo acute dermal irritation study no evidence for skin irritation was noted for T001095. The test item did not meet the criteria for classification as irritant or corrosive according to the criteria of the CLP Regulation (EC) No 1272/2008.
Eye irritation:
According to the in vitro eye irritation study (BCOP) no evidence for eye irritation was noted for T001095. The test item did not meet the criteria for classification as irritant or corrosive according to the criteria of the CLP Regulation (EC) No 1272/2008.
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