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EC number: 947-028-8 | 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
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- Nanomaterial aspect ratio / shape
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- Endpoint summary
- Stability
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- 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
The substance is not classified for skin/eye irritation/corrosion, based on the results of an in vitro eye irritation/corrosion study and an in vitro skin irritation study.
Key value for chemical safety assessment
Skin irritation / corrosion
Link to relevant study records
- Endpoint:
- skin irritation: in vitro / ex vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 17 August 2015 - 24 August 2015
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
- Version / remarks:
- (2013)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)
- Version / remarks:
- (2012)
- Deviations:
- no
- GLP compliance:
- yes
- Test system:
- human skin model
- Source species:
- human
- Cell type:
- other: epidermal keratinocytes
- Vehicle:
- unchanged (no vehicle)
- Details on test system:
- RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
EPISKIN Small ModelTM (EPISKIN-SMTM, 0.38 cm2, Batch no.: 15-EKIN-033; source: SkinEthic Laboratories, Lyon, France). This model is a three-dimensional human epidermis model, which consists of adult human-derived epidermal keratinocytes which have been seeded on a dermal substitute consisting of a collagen type I matrix coated with type IV collagen. The keratinocytes were cultured for 13 days, which resulted in a highly differentiated and stratified epidermis model comprising the main basal, supra basal, spinous and granular layers and a functional stratum corneum.
TESTS FOR INTERFERENCE WITH MTT ENDPOINT
- The test substance was checked for possible colour interference before the study was started. Approximately 10 mg of the test substance was added to 90 µL Milli-Q water. The mixture was mixed for approximately 15 minutes. A negative control, 10 µL Milli-Q water was tested concurrently. At the end of the shaking period a colour check was performed.
- The test substance was checked for possible direct MTT reduction before the study was started. To assess the ability of the test substance to reduce MTT, approx. 10 mg of the test substance was added to 2 mL MTT solution (0.3 mg/mL in PBS). The mixture was incubated for 3 hour at 37°C. A negative control, sterile Milli-Q water was tested concurrently.
APPLICATION/TREATMENT
The test was performed on a total of 3 tissues per test substance together with negative and positive controls. The skin was moistened with 5 μL Milli-Q water (Millipore Corp., Bedford, Mass., USA) to ensure close contact of the test substance to the tissue and the solid test substance (23.4 to 27.2 mg) was added into 12-well plates on top of the skin tissues. Three tissues were treated with 25 μL PBS (negative control) and 3 tissues with 25 μL 5% SDS in PBS (positive control) respectively. The positive control was re-spread after 7 minutes contact time.
REMOVAL OF TEST SUBSTANCE
- Washing: PBS
- Time after start of exposure: 15 minutes
POST INCUBATION PERIOD
42 hours at 37°C
CELL VIABILITY MEASUREMENT
After incubation, cell culture inserts were dried carefully to remove excess medium and were transferred into a 12-wells plate prefilled with 2 mL MTT-medium (0.3 mg/mL in PBS). The tissues were incubated for 3 h at 37°C. After incubation the tissues were placed on blotting paper to dry the tissues. Total biopsy was made by using a biopsy punch. Epidermis was separated from the collagen matrix and both parts were placed in prelabeled microtubes and extracted with 500 μL isopropanol. Tubes were stored refrigerated and protected from light for 69.5 hours. The amount of extracted formazan was determined spectrophotometrically at 570 nm in duplicate with the TECAN Infinite® M200 Pro Plate Reader.
SCORING SYSTEM
Cytotoxicity is expressed as the reduction of mitochondrial dehydrogenase activity measured by formazan production from MTT at the end of the treatment. Cell viability was calculated for each tissue as a percentage of the mean of the negative control tissues. Skin irritation potential of the test substance was classified according to remaining cell viability following exposure of the test substance. - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- TEST MATERIAL
- Amounts applied: 23.4 to 27.2 mg per skin tissue
- The skin tissues were moistened with 5 µL Milli-Q water before application
NEGATIVE CONTOL:
- Amount applied: 25 µL Phosphate buffered saline (PBS)
POSITIVE CONTROL
- Amount applied: 25 µL
- Concentration: 5% (aq) Sodium dodecyl sulphate in PBS - Duration of treatment / exposure:
- 15 minutes
- Duration of post-treatment incubation (if applicable):
- 42 hours
- Number of replicates:
- 3
- Irritation / corrosion parameter:
- % tissue viability
- Run / experiment:
- mean of 3 replicates
- Value:
- 117
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Other effects / acceptance of results:
- Mean tissue viability for the test substance was > 50% (117%), therefore the test substance is considered not to be irritant to the skin.
- Interpretation of results:
- other: the substance does not need to be classified for skin irritation according to GHS and CLP
- Conclusions:
- An in vitro skin irritation test was conducted according to OECD 439 guideline and GLP principles. It is concluded that this test is valid and that the substance is not irritating in the in vitro skin irritation test.
- Executive summary:
In an in vitro skin irritation test using a human skin model (EPISKIN Small Model), conducted according to OECD 439 and GLP principles, the influence of the substance on the viability of human skin was tested. Reliable positive and negative controls were included. The substance was applied directly to 0.38 cm2 cultured skin (23.4 to 27.2 mg, in presence of 5 μL Milli-Q water). After 15 minutes, the substance was removed and cells were cultured for 42 hours at 37°C. The viability of the cells was tested by reduction of MTT. Survival of unexposed skin was set at 100%, the positive control had a mean cell viability of 13% whereas the substance showed cell viability of 117%. Since the mean relative tissue viability after exposure to the substance was above 50%, it is concluded that the substance is not irritating in the in vitro skin irritation test. Based on the results of this study, the substance is not classified for skin irritation according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) and Regulation (EC) No 1272/2008 (CLP Regulation).
- Endpoint:
- skin corrosion: in vitro / ex vivo
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- other:
- Reason / purpose for cross-reference:
- data waiving: supporting information
Referenceopen allclose all
TESTS FOR INTERFERENCE WITH MTT ENDPOINT
As no colour changes were observed in the tests, it was concluded that the test substance did not interact with the MTT endpoint.
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:
- August 3, 2015 - August 4, 2015
- 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)
- Version / remarks:
- (2013)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU method B.47 (Bovine corneal opacity and permeability test method for identifying ocular corrosives and severe irritants)
- Version / remarks:
- (2010)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: The Ocular Toxicity Working Group (OTWG) of ICCVAM and NICEATM, Background Review Document (BRD): current status of in vitro test methods for identifying ocular corrosives and severe irritants: The BCOP Test Method, March 2006
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: In Vitro Techniques in Toxicology Database (INVITTOX) protocol 127. Bovine Opacity and Permeability (BCOP) Assay, 2006
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: Gautheron P., Dukic M., Alix D. and Sina J.F., Bovine corneal opacity and permeability test: An in vitro assay of ocular irritancy. Fundam Appl Toxicol 18:442-449, 1992
- Deviations:
- no
- GLP compliance:
- yes
- Specific details on test material used for the study:
- - pH (1% in water, indicative range): 6.5 - 6.2
- Vehicle:
- physiological saline
- Controls:
- yes, concurrent vehicle
- yes, concurrent positive control
- Amount / concentration applied:
- TEST MATERIAL
- Amount applied: 750 µL of a 20% (w/v) suspension in the vehicle per cornea
NEGATIVE CONTROL
- Amount applied: 750 µL of the vehicle per cornea
POSITIVE CONTROL
- Amount applied: 750 µL of a 20% (w/v) Imidazole solution in the vehicle per cornea - Duration of treatment / exposure:
- 4 hours
- Details on study design:
- TEST SITE
- Isolated bovine cornea
- Corneas that had an initial opacity reading higher than 7 were not used
- Three corneas were used for each treatment group, at random.
REMOVAL OF TEST SUBSTANCE
- Washing: yes, with MEM+phenol red
- Time after start of exposure: 4 hours (at 32 °C)
SCORING SYSTEM:
- After exposure, the cornea was thoroughly rinsed to remove the test substance followed by immediate opacity measurement
- Following the final opacity measurement, permeability of the cornea to Na-fluorescein was evaluated, after another incubation period of 90 minutes at 32 °C. OD490 values of less than 1500 were used in the calculation.
- The mean opacity and mean permeability values (OD490) were used for each treatment group to calculate the mean in vitro score:
Mean in vitro irritancy score (IVIS) = mean opacity value + (15 x mean OD490 value).
- Opacity and permeability values were also evaluated individually
TOOLS USED TO ASSESS SCORES:
- Opacitometer (OP-KIT, MC2, Clermont-Ferrand, France) and microplate reader (TECAN Infinite® M200 Pro Plate Reader)
DATA EVALUATION:
- A test substance that induces a mean IVIS >55 is classified with Eye Irr. Cat. 1 in accordance with the CLP Regulation
- A test substance that induces a mean IVIS ≤ 3 is not classified for Eye irritation in accordance with the CLP Regulation
- For a test substance that induces a mean IVIS of >3 - ≤55, it cannot be concluded whether the substance needs to be classified or not and for these substances, more (in vivo) information is needed - Irritation parameter:
- in vitro irritation score
- Run / experiment:
- mean of 3 replicates
- Value:
- 1
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Interpretation of results:
- other: the substance does not need to be classified for eye irritation/corrosion according to GHS and CLP
- Conclusions:
- Based on the results of a Bovine Corneal Opacity and Permeability test in which the substance did not induce ocular irritation (mean in vitro irritancy score of 1.0), the substance is not classified for eye irritation/corrosion.
- Executive summary:
Using the Bovine Corneal Opacity and Permeability test (BCOP test) the substance was screened for its eye irritancy potential in accordance with OECD 437 and according to GLP principles. The substance was applied as a 20% (w/v) suspension (750 µL) directly on top of the corneas. Adequate negative and positive controls were included. The substance did not induce ocular irritation through both endpoints, resulting in a mean in vitro irritancy score (IVIS) of 1.0 after 240 minutes of treatment. Since the substance induced a mean IVIS ≤ 3, the substance is not classified for eye irritation/corrosion according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) and Regulation (EC) No 1272/2008 (CLP Regulation).
Reference
- Summary of opacity, permeability and in vitro scores:
Treatment |
Mean Opacity |
Mean Permeability |
Mean in vitro Irritation Score |
Negative control |
0.0 |
0.000 |
0.0 |
Positive control |
105.0 |
1.939 |
134.1 |
L 125 PLUS |
1.0 |
-0.003 |
1.0 |
- Individual in vitro irritancy scores:
Eye |
In vitro Irritancy Score |
Negative control |
|
1 |
-0.6 |
2 |
0.3 |
3 |
0.4 |
Positive control |
|
4 |
124.2 |
5 |
132.5 |
6 |
145.6 |
L 125 PLUS |
|
7 |
2.3 |
8 |
-0.8 |
9 |
1.4 |
No pH effect of the test substance was observed on the rinsing medium.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Skin irritation/corrosion
In an in vitro skin irritation test using a human skin model (EPISKIN Small Model), conducted according to OECD 439 and GLP principles, the influence of the substance on the viability of human skin was tested. Reliable positive and negative controls were included. The substance was applied directly to 0.38 cm2cultured skin (23.4 to 27.2 mg, in presence of 5 μL Milli-Q water). After 15 minutes, the substance was removed and cells were cultured for 42 hours at 37°C. The viability of the cells was tested by reduction of MTT. Survival of unexposed skin was set at 100%, the positive control had a mean cell viability of 13% whereas the substance showed cell viability of 117%. Since the mean relative tissue viability after exposure to the substance was above 50%, it is concluded that the substance is not irritating in the in vitro skin irritation test.
This inorganic substance does not have a rate of hydrolysis. Also metabolism is not considered relevant. Therefore the longer incubation period in the in vitro study for skin corrosion will not affect the substance as such and thus, as the substance is not irritating to skin, it is concluded that the substance is also not corrosive to skin.
Eye irritation/corrosion
Using the Bovine Corneal Opacity and Permeability test (BCOP test) the substance was screened for its eye irritancy potential in accordance with OECD 437 and according to GLP principles. The substance was applied as a 20% (w/v) suspension (750 µL) directly on top of the corneas. Adequate negative and positive controls were included. The substance did not induce ocular irritation through both endpoints, resulting in a mean in vitro irritancy score (IVIS) of 1.0 after 240 minutes of treatment. Since the substance induced a mean IVIS ≤ 3, the substance is not classified for eye irritation/corrosion.
Based on the results of this study, performing a second in vitro and/or an in vivo study is not needed. The results obtained from this in vitro study allow a conclusive decision on the classification of the substance.
Justification for classification or non-classification
Based on the results of an in vitro eye irritation/corrosion study and an in vitro skin irritation study, the substance does not need to be classified for skin/eye irritation/corrosion according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) and Regulation (EC) No 1272/2008 (CLP Regulation).
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