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EC number: 807-534-0 | CAS number: 1228284-89-6
- 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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- Endpoint summary
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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
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- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
Skin: Not classified as corrosive, EpiSkin, OECD 431, Hargitai 2015
Skin: Classified as irritant Category 2, EpiSkin, OECD 439, Hargitai 2015
Eye: Not classified as irritant, ICE, OECD 438, Váliczkó 2015
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:
- 2013-12-18 2013-12-20
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: The study was conducted in accordance with OECD guideline 439 and in compliance with GLP. All validity criteria were within acceptable limits.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: COMMISSION REGULATION (EU) No 640/2012 B.46. (2012)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Species:
- human
- Details on test animals or test system and environmental conditions:
- HUMAN SKIN: EPISKIN® (SM) (Manufacturer: SkinEthic, France, Batch No.: 13-EKIN-045, Expiry Date: 23 December 2013) is a three-dimensional human epidermis model. Adult human-derived epidermal keratinocytes are seeded on a dermal substitute consisting of a collagen type I matrix coated with type IV collagen. A highly differentiated and stratified epidermis model is obtained after 13-day culture period comprising the main basal, supra basal, spinous and granular layers and a functional stratum corneum. Its use for skin irritation testing involves topical application of test materials to the surface of the epidermis, and the subsequent assessment of their effects on cell viability.
- Controls:
- yes
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 50 µL - Duration of treatment / exposure:
- 15 mins
- Details on study design:
- Disks of EPISKIN (3 units/chemical) were treated with the test item and incubated for 15 mins at room temperature. Exposure of test material was terminated by rinsing with phosphate buffered saline (PBS). Epidermis units were then incubated at 37°C for 42 hours in an incubator with 5% CO2. The viability of the epidermis on each disk was assessed by incubating the tissues for 3 hours with MTT solution at 37°C in 5% CO2 protected from light. The formazan extract in acidified isopropanol was then spectrophotometrically evaluated for optical density (OD) and quantified.
SDS 5% and PBS treated epidermis were used as positive and negative controls, respectively. An additional disk was used to provide an estimate of colour contribution from the test item. For each treated tissue viability was expressed as a % relative to negative control. If the mean relative viability after 15 minutes exposure and 42 hours post incubation is less or equal (≤) to 50% of the negative control, the test substance is considered to be irritant to skin. - Irritation / corrosion parameter:
- other: other: Mean cell viability
- Value:
- 12
- Remarks on result:
- other:
- Remarks:
- Basis: mean. Remarks: irritant. (migrated information)
- Irritant / corrosive response data:
- The optical density value for the test item treated skin showed a viability of 12±2.31%. In addition, after MTT reduction, the treated discs became white around the edges.
The mean OD value of the three negative control tissues was 0.740. The positive control result showed a mean of 12% viability. Each standard deviation value (SD) of the % viability was below 18. Control OD values were below historically established boundaries. All validity criteria were within acceptable limits and, therefore, the study can be considered as valid.
As the test item was coloured, one additional test item-treated tissue was used for the non specific OD evaluation. Optical density (measured at 540 nm) of this tissue was determined as 0.018, Non Specific Colour % was calculated as 2.4%. Therefore additional data calculation was not necessary.
No colour change was observed after three hours of incubation of the test item in MTT solution. The test material did not interact with the MTT, therefore additional controls and data calculations were not necessary. A false estimation of viability can be precluded. - Interpretation of results:
- Category 2 (irritant) based on GHS criteria
- Remarks:
- Migrated information
- Conclusions:
- In this in vitro EPISKIN®(SM) model test, the results indicate that the test item is Irritant (UN GHS: Category 2).
- Executive summary:
The reconstructed human epidermis model EPISKIN® (SM) is designed to predict and classify the skin irritant potential of chemicals, by measuring its cytotoxic effect, as reflected in the MTT assay, on the EPISKIN reconstituted human epidermis. This method is approved by international regulatory agencies as a replacement for the identification of irritants / corrosives in the in vivo Rabbit skin assay (OECD 404).
Disks of EPISKIN (3 units / chemical) were treated with the test item and incubated for 15 minutes at room temperature. Exposure of test material was terminated by rinsing with phosphate buffered saline (PBS). Epidermis units were then incubated at 37°C for 42 hours in an incubator with 5% CO2. The viability of the epidermis on each disk was assessed by incubating the tissues for 3 hours with MTT solution at 37°C in 5% CO2 protected from light. The formazan extract in acidified isopropanol was then spectrophotometrically evaluated for optical density (OD) and quantified. SDS 5% and PBS treated epidermis were used as positive and negative controls, respectively. An additional disk was used to provide an estimate of colour contribution from the test item. For each treated tissue viability was expressed as a % relative to negative control. If the mean relative viability after 15 minutes exposure and 42 hours post incubation is less or equal (≤) to 50% of the negative control, the test substance is considered to be irritant to skin.
Following exposure with the test item, the mean cell viability was 12% compared to the negative control and, therefore, irritant. In addition, after MTT reduction, the treated discs became white around the edges.
All validity criteria were within acceptable limits and therefore the study can be considered as valid.
In this in vitro EPISKIN®(SM) model test, the results indicate that the test item is Irritant (UN GHS: Category 2).
Reference
Table 1: Optical Density (OD) and the calculated % viability of the cells
Substance |
Optical density |
Viability (%) |
|
Negative control (PBS) |
1 |
0.770 |
104 |
2 |
0.728 |
98 |
|
3 |
0.721 |
97 |
|
mean ± SD |
0.740 |
100±3.79 |
|
Positive control (5% SDS) |
1 |
0.100 |
14 |
2 |
0.095 |
13 |
|
3 |
0.070 |
9.5 |
|
mean ± SD |
0.088 |
12±2.36 |
|
Test item |
1 |
0.107 |
14 |
2 |
0.071 |
9.6 |
|
3 |
0.093 |
13 |
|
mean ± SD |
0.090 |
12±2.31 |
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed (irritating)
Eye irritation
Link to relevant study records
- Endpoint:
- eye irritation
- Remarks:
- in vitro
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2013-12-02 until 2015-06-14
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: The study was carried out in accordance with OECD guideline 438 and in cimpliance with GLP. The validity criteria have been fulfilled.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 438 (Isolated Chicken Eye Test Method for Identifying Ocular Corrosives and Severe Irritants)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.2400 (Acute Eye Irritation)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU method B.48 (Isolated chicken eye test method for identifying occular corrosives and severe irritants)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Species:
- other: Isolated chicken eye
- Strain:
- other: ROSS 308
- Details on test animals or tissues and environmental conditions:
- EYES
- Source: Commercial abattoir
EXPERIMENTAL DATES: 2 December 2013 - Vehicle:
- unchanged (no vehicle)
- Controls:
- other: Yes (0.9% sodium chloride solution)
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 30 μL - Duration of treatment / exposure:
- 10 seconds
- Observation period (in vivo):
- 240 minutes. The negative and positive control eyes and all test eyes were evaluated pre-treatment and at approximately 30, 75, 120, 180 and 240 minutes after the post-treatment rinse. Corneal thickness and corneal opacity were measured at all time points. Fluorescein retention was measured on two occasions, at base line (t=0) and approximately 30 minutes after the post-treatment rinse.
- Number of animals or in vitro replicates:
- 7 isolated eyes (3 test item, 3 positive control, 1 negative control)
- Details on study design:
- METHOD
- After the zero reference measurements, the eye was held in a horizontal position and 30 μL of test item was applied onto the centre of the cornea such that the entire surface of the cornea was covered. After 10 seconds, the surface was rinsed with saline. The positive control eyes were treated in a similar way with 30 μL benzalkonium chloride 5 % (w/v). The negative control eye was treated with 30 μL of sodium chloride (0.9% solution). Corneal thickness, corneal opacity and fluorescein retention were measured and any morphological effects (pitting or loosening of the epithelium) evaluated.
REMOVAL OF TEST SUBSTANCE
- Washing (if done): After the 10 second exposure period, the cornea surface was rinsed thoroughly with 20 mL isotonic saline at ambient temperature.
SCORING SYSTEM:
- Corneal thickness or swelling. Measurements made with an optical pachymeter on a slit-lamp microscope and expressed as a percentage calculated from corneal thickness measurements. Corneal swelling was classified by the following scale: Mean cornea swelling (%) of 0-5, >5-12, >12-18 (>75 mins after treatment), >12-18 (<75 mins after treatment), >18-26, >26-32 (>75 mins after treatment), >26-32 (<75 mins after treatment), >32 classified as ICE Class I, II, II, III, III, III, IV or IV, respectively. i.e. No swelling = Class I, slight swelling = Class II, moderate swelling = Class III, severe swelling = Class IV.
- Corneal opacity. Corneal opacity was scored (on a 0-4 scale) using the area of the cornea that was most densely opacified and the mean ΔCOmax (mean value of the highest opacity scores) calculated. Mean maximum opacity scores of 0-0.5, 0.6-1.5, 1.6-2.5 and 2.6-4.0 were classified as ICE Class I, II, III and IV, respectively. i.e. No opacity = Class I, Slight opacity = Class II, Moderate opacity = Class III, Severe or total opacity = Class 4.
- Fluorescein retention: Fluorescein retention change was calculated and scored using a 0-3 scale. Mean fluorescein retention scores of 0-0.5, 0.6-1.5, 1.6-2.5 and 2.6-3.0 were classified as ICE Class I, II, III and IV, respectively. i.e. No fluorescein retention = Class I, slight fluorescein retention = Class II, Moderate fluorescein retention = Class III, Severe fluorescein retention = Class IV.
TOOL USED TO ASSESS SCORE: Hand-slit lamp / fluorescein - Irritation parameter:
- other: Mean maximum corneal swelling
- Basis:
- mean
- Time point:
- other: up to 75 minutes
- Score:
- 0
- Remarks on result:
- other: ICE Class I
- Irritation parameter:
- other: Mean maximum corneal swelling
- Basis:
- mean
- Time point:
- other: up to 240 minutes
- Score:
- 0
- Remarks on result:
- other: ICE Class I
- Irritation parameter:
- other: Mean maximum corneal opacity change
- Basis:
- mean
- Score:
- 0.67
- Remarks on result:
- other: ICE Class II
- Irritation parameter:
- other: Mean fluorescein retention change
- Basis:
- mean
- Score:
- 0
- Remarks on result:
- other: ICE Class I
- Irritation parameter:
- other: Overall ICE Class
- Remarks on result:
- other: 2xI, 1xII
- Irritant / corrosive response data:
- No corneal swelling or fluorescein retention was observed during the four hour observation period. Corneal opacity (severity 0.5 or 1) was noted in all eyes. No other corneal effect was observed. The negative and positive control group results demonstrate that the study was valid.
The test item is non-irritating, GHS Classification: Non-classified.
The positive control benzalkonium chloride 5% (w/v) was classed as severely irritating, GHS Classification: Category 1.
The negative control Saline (NaCl 0.9% w/v) was classed as non-irritating, GHS Classification: Non-classified. - Interpretation of results:
- study cannot be used for classification
- Remarks:
- Migrated information: non-irritant
- Conclusions:
- Based on this in vitro eye irritation study in isolated chicken eyes, the test item is non-irritating, GHS Classification: Non-classified.
- Executive summary:
An in vitro eye irritation study was performed in isolated chicken’s eyes. The irritation effects of the test item were evaluated according to OECD 438 (2013). After the zero reference measurements, the eye was held in a horizontal position and 30 μL of test item was applied onto the centre of the cornea such that the entire surface of the cornea was covered. After 10 seconds, the surface was rinsed with saline. The positive control eyes were treated in a similar way with 30 μL benzalkonium chloride 5 % (w/v). The negative control eye was treated with 30 μL of sodium chloride (0.9% solution). Corneal thickness, corneal opacity and fluorescein retention were measured and any morphological effects (pitting or loosening of the epithelium) evaluated.
No corneal swelling or fluorescein retention was observed during the four hour observation period. Corneal opacity (severity 0.5 or 1) was noted in all eyes. No other corneal effect was observed. The negative and positive control group results demonstrated that the study was valid.
Based on this in vitro eye irritation study in isolated chicken eyes, the test item is non-irritating, GHS Classification: Non-classified.
Reference
Table 1: Mean values of the treated eyes for maximum corneal thickness change, corneal opacity change and fluorescein retention change – Run 1
Observation |
Test item |
Positive control |
Negative control |
|||
Value |
ICE Class |
Value |
ICE Class |
Value |
ICE Class |
|
Mean maximum corneal swelling at up to 75 min |
0% |
I |
0% |
I |
0% |
I |
Mean maximum corneal swelling at up to 240 min |
0% |
I |
-5.3% |
II |
0% |
I |
Mean maximum corneal opacity change |
0.67 |
II |
4.00 |
IV |
0 |
I |
Mean fluorescein retention change |
0 |
I |
2.83 |
IV |
0 |
I |
Other Observations |
None |
Loosening of epithelium observed in all eyes (3/3) 75 mins after post-treatment rinse. |
None |
|||
Overall ICE Class |
2xI 1xII |
1xII 2xIV |
3xI |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Additional information
Skin Irritation / Corrosion
Two studies are available, both performed in compliance with GLP, using recent guideline methods which are validated for regulatory use:
In order to assess the in vitro skin corrosion potential of the substance, EpiSkin disks (Hargitai 2015) were treated with the test item, negative controls (0.9 % sodium chloride) and positive controls (glacial acetic acid) and incubated for four hours at room temperature (two replicates each). The mean cell viability was 92 % compared to the negative control (100 %) and the positive control (0.7 %). All validity criteria were within acceptable limits and therefore the study can be considered as valid. The substance is not corrosive to the in vitro skin model EpiSkin.
In order to assess the in vitro skin irritation potential of the substance, EpiSkin disks (Hargitai 2015) were treated with the test item, negative controls (PBS) and positive controls (5% SDS) for 15 min (three replicates each). The mean cell viability was 12 ± 2.31% compared to the negative control (100 ± 3.79%) and the positive control (12 ± 2.36%). All validity criteria were within acceptable limits and therefore the study can be considered as valid. The substance is considered irritant to the in vitro skin model EpiSkin.
Based on the available in vitro data which is considered to be adequate, reliable and conclusive for skin irritation/corrosion, the substance is considered to be an irritant. The results is carried forward for the purposes of risk assessment, and classification.
Eye Irritation
In order to assess thein vitroeye irritation potential of the substance, OECD Guideline 438 Isolated Chicken Eye Test Method was carried out by Váliczkó (2015). Simultaneously were performed three tests with the substance, three positive controls (benzalkonium chloride 5 % (w/v)) and one negative control (0.9 % sodium chloride) on isolated eyes. No corneal swelling or fluorescein retention was observed during the four hour observation period. Corneal opacity (severity 0.5 or 1) was noted in all eyes. No other corneal effect was observed. The negative and positive control group results demonstrated that the study was valid.
Based on the available in vitro data which is considered to be adequate, reliable and conclusive for eye irritation, the substance is considered to not be an irritant. The result is carried forward for the purposes of risk assessment, and classification.
Justification for selection of skin irritation / corrosion endpoint:
GLP compliant, guideline study, no restrictions, fully adequate for assessment.
Justification for selection of eye irritation endpoint:
GLP compliant, guideline study, no restrictions, fully adequate for assessment.
Effects on skin irritation/corrosion: irritating
Justification for classification or non-classification
Skin Irritation / Corrosion
Two EpiSkin studies were conducted following OECD guidelines and in compliance with GLP Directive 2004/10/EC. Both results are valid, reliable and adequate for the purpose of risk assessment, classification and labelling.
According to the criteria set in OECD Guideline 439, section 36 - Interpretation of Results and Prediction Model, the test chemical is considered to be irritant to skin under UN GHS Category 2. The result is conclusive.
Eye Irritation
Results from a validated study for eye irritation on Isolated Chicken Eye, conducted according to OECD Guideline demonstrated the substance to be non-irritating to the eye. The conclusion is considered valid, reliable and adequate for the purpose of risk assessment, classification and labelling.
According to the criteria set in OECD Guideline 438, Section 51 - Decision Criteria, Table 6: Overall in vitro classifications, the test chemical is considered not to be classified under UN GHS.The result is conclusive.
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