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EC number: 815-500-1 | CAS number: 1853175-99-1
- 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
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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: not irritating (OECD 404, GLP, K, Rel.1) and (OECD 439, GLP, K, Rel.1)
Eye irritation: not irritating (OECD 405, GLP, K, Rel.1)
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:
- 20 July - 14 August 2015
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
- Remarks:
- GLP study performed according to OECD Guideline 439.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
- Version / remarks:
- 26 July 2013
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)
- Version / remarks:
- 24 August 2009
- Deviations:
- no
- Principles of method if other than guideline:
- Not applicable
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- 08 April 2015.
- Test system:
- human skin model
- Remarks:
- Epi-200 Kit
- Source species:
- human
- Cell type:
- non-transformed keratinocytes
- Cell source:
- other: reconstructed epidermis
- Vehicle:
- unchanged (no vehicle)
- Details on test system:
- RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE:
Supplier: MatTek In Vitro Life Science Laboratories, Bratislava.
Date received: 14 August 2015
EpiSkinTM Tissues (0.38cm2) lot number: 21685
Maintenance Medium lot number: 1660120
Assay Medium lot number: 080615ZSD
EVALUATION OF DIRECT INTERACTION WITH MTT
- For correct interpretation of results it was necessary to assess the ability of the test item to directly reduce MTT. The direct interaction of MTT with the test item was checked by adding 30 µL of the test item to 1mL of the solution of MTT. No colour change could be observed in the present study. Therefore, there is no direct interaction between the test item and MTT
TREATMENT
- After approximately 18 hours incubation of the tissues, they were treated with the test item.
- 1 plate (3 tissues) was used as negative control; each tissue was treated with 30 μL DPBS buffer, a nylon mesh was added in order to ensure sufficient contact with the tissue sur-face.
- 1 plate was used as positive control; each tissue was treated with 30 μL SDS-solution, a nylon mesh was added in order to ensure sufficient contact with the tissue surface.
- 1 plate was used for treatment with the test item: 30 μL test item were applied, and a nylon mesh was added in order to ensure sufficient contact with the tissue surface.
Tissues were dosed in 1-min-intervals. After dosing the last tissue, all plates are trans-ferred into the incubator for 35 min at 37 ± 1°C and 5.0 ± 0.5% CO2. 60 min after the first application, the inserts were removed from the plates using sterile forceps and rinsed im-mediately in 1-min-intervals. After rinsing, each tissue was dried with a sterile cotton tip and then transferred into a new 6-well-plate with fresh assay medium (0.9 mL). Then, the tissues were set in the incubator for 24 h.
REMOVAL OF TEST MATERIAL AND CONTROLS
- For 3 incubated tissues, a new 6-well-plate with 0.9 mL assay medium in the upper row was prepared. The tissues were removed from the incubator and shaken for 10 min (500 rpm). Then the inserts were transferred into the new 6-well-plate and set into the in-cubator for 18 h for post-incubation.
MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- After a total incubation time of 42 h, a 24-well-plate was prepared with 300 μL freshly pre-pared MTT-reagent in each well. The tissues were blotted on the bottom and then trans-ferred into the 24-well-plate. Then the 24-well-plate was set into the incubator for 3 h at 37 ± 1°C and 5.0 ± 0.5% CO2.
- After 2 h, the inserts in which formazan had been produced were pierced with an injection needle, taking care that all colour was extracted. The inserts were then discarded and the content of each well was thoroughly mixed in order to achieve homogenisation.
- From each well, two replicates with 200 μL solution (each) were pipetted into a 96-well-plate which was read in a plate spectral photometer at 570 nm.
VIABILITY CALCULATION:
- Data from individual replicate tissues (OD values and calculated percent tissue viability data for the test item and controls), mean percent tissue viability and standard deviation for each individual test item and control were reported in Table 7.3.1/1. The results were expressed as a viability percentage compared with the negative control: viability % = (mean OD test item / mean OD negative control) * 100
ACCEPTABILITY OF THE ASSAY
- The absolute OD 570 nm of the negative control tissues in the MTT test is an indicator of tissue viability obtained after the shipping procedure and under specific conditions of the assay. Tissue viability is meeting the acceptance criterion if the mean OD of the two tissues is ≥ 0.8 and <=2.8.
The % Formazan production of positive control SDS is <=20% of negative control and the variation within replicates (RSD) is < 18%. - Control samples:
- yes, concurrent negative control
- yes, concurrent positive control
- Amount/concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 30 µL
- Concentration (if solution): Undiluted - Duration of treatment / exposure:
- 60 minutes at 37 +/-1°C.
- Duration of post-treatment incubation (if applicable):
- 18 hours post-incubation period at 37°+/-1°C, 5 +/-0.5% CO2
- Number of replicates:
- 3
- Irritation / corrosion parameter:
- % tissue viability
- Remarks:
- mean
- Run / experiment:
- mean value
- Value:
- 100.9
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- valid
- Positive controls validity:
- valid
- Remarks on result:
- no indication of irritation
- Other effects / acceptance of results:
- MTT VIABILITY ASSAY RESULTS
- The test item is considered as not skin irritant.
- After the treatment, the relative absorbance values were increased to 100.9%. This value is well above the threshold for skin irritation (50%).The optical density of the negative control was well within the required acceptability criteri-on of 0.8 ≤ mean OD ≤ 2.8, OD was 1.8. The positive control induced a decrease in the relative absorbance as compared to the negative control to 3.3 % (required: ≤ 20%) for thus ensuring the validity of the test system. Variation within replicates was within the ac-cepted range for negative control, positive control and test item. - Interpretation of results:
- GHS criteria not met
- Conclusions:
- Under the test conditions, test material is not classified according to Regulation (EC) No. 1272/2008 (CLP).
- Executive summary:
An in vitro skin irritation test using the Reconstructed Human Epidermis (Episkin Standard model) was performed according to the OECD Guideline 439 and in compliance with GLP to predict the acute skin irritation potential of the test item.
The test item was applied at the dose of 30 µL, to 3 tissues of the Human skin model EpiDerm during 60 minutes, followed by a rinse with 25 mL of PBS and a 18 hours post-incubation period at 37+/-1°C, 5 +/-0.5% CO2. Cell viability was then measured by enzymatic conversion of the vital dye MTT into a blue formazan salt that was quantitatively measured after extraction from tissues.
The mean corrected percent viability of the treated tissues was 100.9%, versus 3.3% in the positive control (5% Sodium Dodecyl Sulfate).
Under the test conditions and in accordance with Regulation EC No. 1272/2008, the test item was considered as non-irritant to skin.
- Endpoint:
- skin irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Between 21 July and 11 August, 2015.
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Remarks:
- GLP study conducted in compliance with OECD Guideline No. 404 without any deviation.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
- Version / remarks:
- 24 April 2002
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
- Version / remarks:
- 30 May 2008
- Deviations:
- no
- Principles of method if other than guideline:
- Not applicable
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Inspected on 2015-04-23&24 / Signed on 2015-10-23
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: EUROLAP (F-35140 GOSNE)
- Weight at study initiation: 2.10 - 3.37 kg
- Housing: Each animal was kept in an individual box installed in conventional air conditioned animal husbanding.
- Diet: foodstuff (SAFE - 112), ad libitum
- Water: tap-water, ad libitum
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature: 17-23 °C
- Humidity: 30-70 %
- Air changes: at least 10 changes per hour.
- Photoperiod: 12 hours light/12 hours dark.
IN-LIFE DATES: From 21 July to 11 August, 2015. - Type of coverage:
- semiocclusive
- Preparation of test site:
- clipped
- Vehicle:
- unchanged (no vehicle)
- Controls:
- yes
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): Test item was applied as supplied. - Duration of treatment / exposure:
- 4 hours
- Observation period:
- Skin reactions were appreciated 1, 24, 48 and 72 hours after removal of the patch and observations were continued from Days 4 to 14 (in case of persistent reactions were observed).
- Number of animals:
- 3 females
- Details on study design:
- PRETEST
Initially, a single animal was treated. After consideration of the cutaneous responses produced in the first treated animal, two additional animals were treated.
TEST SITE
- Area of exposure: Undamaged skin area of the right flank of each animal
- Type of wrap if used: Patch was secured in position with a strip of surgical adhesive tape.
REMOVAL OF TEST SUBSTANCE
- Washing: After removal of the patch, the treated area was rinsed with distilled water.
- Time after start of exposure: 4 h
OBSERVATION TIME POINTS
1, 24, 48 and 72 hours after removal of the patch and observations were continued from Days 4 to 14 (in case of persistent reactions were observed).
SCORING SYSTEM:
- Method of calculation: Skin irritant reaction was scored as per Draize scale according to OECD guideline 404 - Irritation parameter:
- erythema score
- Basis:
- animal #1
- Remarks:
- mean individual score
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 4
- Reversibility:
- fully reversible within: 7 days
- Remarks on result:
- probability of mild irritation
- Irritation parameter:
- edema score
- Basis:
- animal #1
- Remarks:
- mean individual score
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 4
- Reversibility:
- fully reversible within: 7 days
- Remarks on result:
- probability of mild irritation
- Irritation parameter:
- erythema score
- Basis:
- animal #2
- Remarks:
- mean individual score
- Time point:
- 24/48/72 h
- Score:
- 2
- Max. score:
- 4
- Reversibility:
- not fully reversible within: 7 days.
- Remarks on result:
- probability of mild irritation
- Irritation parameter:
- edema score
- Basis:
- animal #2
- Remarks:
- mean individual score
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 4
- Reversibility:
- fully reversible within: 7 days
- Remarks on result:
- probability of weak irritation
- Irritation parameter:
- erythema score
- Basis:
- animal #3
- Remarks:
- mean individual score
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 4
- Reversibility:
- fully reversible within: 7 days
- Remarks on result:
- probability of weak irritation
- Irritation parameter:
- edema score
- Basis:
- animal #3
- Remarks:
- mean individual score
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 4
- Reversibility:
- fully reversible within: 7 days
- Remarks on result:
- probability of weak irritation
- Irritant / corrosive response data:
- - Slight to well - defined erythema associated with a very slight to slight oedema was noted on the treated area of all animals, 1 hour after the patch removal. All reactions were totally reversible on day 7.
- On the cutaneous structure, loss of litheness was noted in one animal on day 3 and dryness of the skin in all animals on day 7. The skin recovered a normal aspect on day 14 in two animals but dryness of the skin was still noted on the day 14 in one animal. - Other effects:
- None
- Interpretation of results:
- Category 3 (mild irritant) based on GHS criteria
- Conclusions:
- Under the test conditions, test item must not be classified according to CLP Regulation (EC) No. 1272/2008 and classified as "Category 3 (mild irritant)" based on Globally Harmonized System (GHS).
- Executive summary:
In a dermal irritation study performed according to the OECD Guideline No. 404, and in compliance with GLP, 0.5 mL of undiluted test item was applied on an undamaged skin area of the flank of 3 female New Zealand White rabbits. On the other flank an untreated area was served as the control. Test sites were covered with a semi-occlusive dressing for 4 h. Skin irritation was assessed and scored according to the Draize scale at 1, 24, 48 and 72 hours after removal of the patch and observations were continued from Days 4 to 14. Initially, a single animal was treated. After consideration of the cutaneous responses produced in the first treated animal, two additional animals were treated.
Slight to well - defined erythema associated with a very slight to slight oedema was noted on the treated area of all animals, 1 hour after the patch removal. All reactions were totally reversible on day 7. On the cutaneous structure, loss of litheness was noted in one animal on day 3 and dryness of the skin in all animals on day 7. The skin recovered a normal aspect on day 14 in two animals but dryness of the skin was still noted on the day 14 in one animal.
The mean scores for each animal within 3 scoring times (24, 48 and 72 h) were 2.0 / 2.0 / 1.0 for erythema and 2.0 / 1.0 / 1.0 for oedema. These effects are reversible on day 7.
Under the test conditions, test item must not be classified according to CLP Regulation (EC) No. 1272/2008 and classified as "Category 3 (mild irritant)" based on Globally Harmonized System (GHS).
This study is considered as acceptable and satisfies the requirement for skin irritation endpoint.
Referenceopen allclose all
Table 7.3.1/&: Absorbance Values negative control, test item and positive control (OD at 570 nm):
Designation | Measurement | Negative Con-trol | Test susbtance | Positive Control |
Tissue 1 | 1 | 1.925 | 1.718 | 0.101 |
2 | 1.922 | 1.727 | 0.102 | |
Tissue 2 | 1 | 1.830 | 1.900 | 0.098 |
2 | 1.857 | 1.924 | 0.097 | |
Tissue 3 | 1 | 1.804 | 1.977 | 0.087 |
2 | 1.800 | 1.989 | 0.088 |
Table 7.3.1/2 Mean Absorbance Values
Designation | Negative Control | Test susbtance | Positive Control |
Mean – blank (tissue 1) | 1.888 | 1.687 | 0.066 |
Mean – blank (tissue 2) | 1.808 | 1.876 | 0.062 |
Mean – blank (tissue 3) | 1.766 | 1.947 | 0.052 |
Mean of the three tissues | 1.821 | 1.837 | 0.060 |
Relative standard deviation of the three tissues | 3.4% | 7.3% | 12.0% |
Table 7.3.1/3 % Formazan Production
Designation | Test susbtance | Positive Control |
% Formazan production (tissue 1) | 92.6% | 3.6% |
% Formazan production (tissue 2) | 103.0% | 3.4% |
% Formazan production (tissue 3) | 106.9% | 2.9% |
% Formazan production (mean) | 100.9% | 3.3% |
Table 7.3.1/4 Validity criteria and results
Criterion | Demanded | Found |
OD of negative control | ≥ 0.8 and ≤ 2.8 | 1.8 |
% Formazan production of positive control SDS | ≤ 20% of negative control | 3.3% |
Variation within replicates (RSD) | < 18% | 3.4% (negative control) 12.0% (positive control) 7.3% (test item) |
Table 7.3.1/1: Individual and mean skin reactions/Erythema - Eschar formation following 4 hour exposure
Skin reaction |
Observation time (following patch removal) |
Individual Scores – Rabbit Number and Sex |
||
A5225/Female |
A5203/Female |
A5264/Female |
||
Erythema/Eschar formation |
1 h |
2 |
1 |
1 |
24 h |
2 |
2 |
1 |
|
48 h |
2 |
2 |
1 |
|
72 h |
2 |
2 |
1 |
|
Day 7 |
0 |
0 |
0 |
|
Total (24, 48 and 72 hours) |
6 |
6 |
3 |
|
Mean (24, 48 and 72 hours) |
2 |
2 |
1 |
Table 7.3.1/2: Individual and mean skin reactions/Oedema formation following 4 hour exposure
Skin reaction |
Observation time (following patch removal) |
Individual Scores – Rabbit Number and Sex |
||
A5225/Female |
A5203/Female |
A5264/Female |
||
Oedema formation |
1 h |
2 |
2 |
1 |
24 h |
2 |
1 |
1 |
|
48 h |
2 |
1 |
1 |
|
72 h |
2 |
1 |
1 |
|
Day 7 |
0 |
0 |
0 |
|
Total (24, 48 and 72 hours) |
6 |
3 |
3 |
|
Mean (24, 48 and 72 hours) |
2 |
1 |
1 |
Note:
A5225: dryness from D7 to D14
A5203: dryness at D7
A5264: dryness at D7. Loss of litheness at D3.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Eye irritation
Link to relevant study records
- Endpoint:
- eye irritation: in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Between 27 July and 06 August, 2015.
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Remarks:
- GLP study conducted in compliance with OECD Guideline No. 405 without any deviation.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 405 (Acute Eye Irritation / Corrosion)
- Version / remarks:
- 02 October 2012.
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
- Deviations:
- no
- Principles of method if other than guideline:
- Not applicable
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Inspected on 2015-04-23&24 / Signed on 2015-10-23
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or tissues and environmental conditions:
- TEST ANIMALS
- Source: EUROLAP (F-35140 GOSNE)
- Weight at study initiation: no data.
- Housing: Each animal was kept in an individual box installed in conventional air conditioned animal husbanding.
- Diet: foodstuff (SAFE - 112), ad libitum
- Water: tap-water, ad libitum
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature: 17-23 °C
- Humidity: 30-70 %
- Air changes: at least ten changes per hour.
- Photoperiod: 12 hours light/12 hours dark.
IN-LIFE DATES: from 27 July to 06 August, 2015. - Vehicle:
- unchanged (no vehicle)
- Controls:
- yes
- Amount / concentration applied:
- TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): Test item was instilled, as supplied - Duration of treatment / exposure:
- No washing was done
- Observation period (in vivo):
- Ocular examinations were performed on both right and left eyes 1, 24, 48 and 72 h & Days 7, 14 and 21 following treatment, according to a numerical evaluation.
- Number of animals or in vitro replicates:
- 3 females
- Details on study design:
- TREATMENT
- 0.1 mL of the test item was instilled, as supplied, into the conjunctival sac of one eye. The other eye remained untreated serving as control.
- Initially, a single animal was treated. After consideration of the ocular responses produced in the first treated animal, two additional animals were treated.
REMOVAL OF TEST SUBSTANCE
- Washing: No
SCORING SYSTEM: According to OECD guideline 405 - Irritation parameter:
- cornea opacity score
- Basis:
- animal #1
- Remarks:
- mean individual score
- Time point:
- 24/48/72 h
- Score:
- 0.7
- Max. score:
- 4
- Reversibility:
- fully reversible within: 2 days
- Remarks on result:
- probability of weak irritation
- Irritation parameter:
- iris score
- Basis:
- animal #1
- Remarks:
- mean individual score
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Reversibility:
- other: not applicable
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #1
- Remarks:
- mean individual score
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 3
- Reversibility:
- fully reversible within: 7 days
- Remarks on result:
- probability of weak irritation
- Irritation parameter:
- chemosis score
- Basis:
- animal #1
- Remarks:
- mean individual score
- Time point:
- 24/48/72 h
- Score:
- 1
- Max. score:
- 4
- Reversibility:
- fully reversible within: 7 days
- Remarks on result:
- probability of weak irritation
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #2
- Remarks:
- mean individual score
- Time point:
- 24/48/72 h
- Score:
- 0.3
- Max. score:
- 4
- Reversibility:
- fully reversible within: 2 days.
- Remarks on result:
- probability of weak irritation
- Irritation parameter:
- iris score
- Basis:
- animal #2
- Remarks:
- mean individual score
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Reversibility:
- other: not applicable.
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #2
- Remarks:
- mean individual score
- Time point:
- 24/48/72 h
- Score:
- 0.7
- Max. score:
- 3
- Reversibility:
- fully reversible within: 2 days
- Remarks on result:
- probability of weak irritation
- Irritation parameter:
- chemosis score
- Basis:
- animal #2
- Remarks:
- mean individual score
- Time point:
- 24/48/72 h
- Score:
- 0.7
- Max. score:
- 4
- Reversibility:
- fully reversible within: 2 days.
- Remarks on result:
- probability of weak irritation
- Irritation parameter:
- cornea opacity score
- Basis:
- animal #3
- Remarks:
- mean individual score
- Time point:
- 24/48/72 h
- Score:
- 0.3
- Max. score:
- 4
- Reversibility:
- fully reversible within: 2 days
- Remarks on result:
- probability of weak irritation
- Irritation parameter:
- iris score
- Basis:
- animal #3
- Remarks:
- mean individual score
- Time point:
- 24/48/72 h
- Score:
- 0
- Max. score:
- 2
- Reversibility:
- other: not applicable
- Remarks on result:
- no indication of irritation
- Irritation parameter:
- conjunctivae score
- Basis:
- animal #3
- Remarks:
- mean individual score
- Time point:
- 24/48/72 h
- Score:
- 0.3
- Max. score:
- 3
- Reversibility:
- fully reversible within: 2 days
- Remarks on result:
- probability of weak irritation
- Irritation parameter:
- chemosis score
- Basis:
- animal #3
- Remarks:
- mean individual score
- Time point:
- 24/48/72 h
- Score:
- 0.3
- Max. score:
- 4
- Reversibility:
- fully reversible within: 2 days
- Remarks on result:
- probability of weak irritation
- Irritant / corrosive response data:
- The ocular reactions observed during the study have been slight to moderate and totally reversible:
- at the conjunctivae level: a slight to moderate redness noted 1 hour after the test item instillation and totally reversible between days 2 and 7, associated with a slight to moderate chemosis noted 1 or 24 hours after the test item instillation and totally reversible between days 2 and 7;
- at the iris level: a congestion, noted 1 hour after the test item instillation in one animal, and totally reversible on day 1.
- at the corneal level: a slight to moderate corneal opacity, noted 24 hours after the test item instillation and totally reversible on day 2. - Other effects:
- None
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Under the test conditions, the test material is not classified as irritating to eyes according to the annex I of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.
- Executive summary:
In an eye irritation study conducted according to OECD 405 guideline and in compliance with GLP, 3 New Zealand White female rabbits were exposed to 0.1 mL of test item in one eye while the contralateral eye remained untreated and served as control. The eyes were examined and the changes were observed at 1, 24, 48, 72 h and day 7 following treatment and graded according to the Draize method. Initially, a single animal was treated. After consideration of the ocular responses produced in the first treated animal, two additional animals were treated.
A slight to moderate redness noted 1 hour after the test item instillation and totally reversible between days 2 and 7, associated with a slight to moderate chemosis noted 1 or 24 hours after the test item instillation and totally reversible between days 2 and 7. At the iris level, a congestion was noted 1 hour after the test item instillation in one animal, and totally reversible on day 1. A slight to moderate corneal opacity, noted 24 hours after the test item instillation and totally reversible on day 2.
Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 0.7, 0.3, 0.3 for cornea score; 0.0, 0.0, 0.0 for iris score; 1.0, 0.7, 0.3 for conjunctivae score and 1.0, 0.7, 0.3 for chemosis score. These effects are reversible between days 2 and 7.
Under the test conditions, the test material is not classified as irritating to eyes according to the annex I of 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.
Reference
Table 7.3.2/1: Individual and Mean Scores for Cornea, Iris and Conjunctivae
Rabbit Number and Sex
|
Time After Treatment
|
Corneal Opacity
|
Iris lesion |
Conjunctival Redness
|
Conjunctival Chemosis
|
A5235 Female
|
1 h |
0 |
1 |
1 |
1 |
24 h |
2 |
0 |
1 |
1 |
|
48 h |
0 |
0 |
1 |
1 |
|
72 h |
0 |
0 |
1 |
1 |
|
Day 7 |
0 |
0 |
0 |
0 |
|
Total (24, 48 and 72 h) |
2 |
0 |
3 |
3 |
|
Mean (24, 48 and 72 h) |
0.7 |
0.0 |
1 |
1 |
Rabbit Number and Sex
|
Time After Treatment
|
Corneal Opacity
|
Iris lesion |
Conjunctival Redness
|
Conjunctival Chemosis
|
A5266 Female
|
1 h |
0 |
0 |
2 |
1 |
24 h |
1 |
0 |
2 |
2 |
|
48 h |
0 |
0 |
0 |
0 |
|
72 h |
0 |
0 |
0 |
0 |
|
Day 7 |
0 |
0 |
0 |
0 |
|
Total (24, 48 and 72 h) |
1 |
0 |
2 |
2 |
|
Mean (24, 48 and 72 h) |
0.3 |
0.0 |
0.7 |
0.7 |
Rabbit Number and Sex
|
Time After Treatment
|
Corneal Opacity
|
Iris lesion |
Conjunctival Redness
|
Conjunctival Chemosis
|
A5270 Female
|
1 h |
0 |
0 |
1 |
1 |
24 h |
1 |
0 |
1 |
1 |
|
48 h |
0 |
0 |
0 |
0 |
|
72 h |
0 |
0 |
0 |
0 |
|
Day 7 |
0 |
0 |
0 |
0 |
|
Total (24, 48 and 72 h) |
1 |
0 |
1 |
1 |
|
Mean (24, 48 and 72 h) |
0.3 |
0 |
0.3 |
0.3 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Respiratory irritation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Skin irritation:
- In vitro:
A key study was identified (Laus, 2015). This in vitro skin irritation test using the Reconstructed Human Epidermis (Standard model) was performed according to the OECD Guideline 439 and in compliance with GLP to predict the acute skin irritation potential of the test item.
The mean corrected percent viability of the treated tissues was 100.9%, versus 3.3% in the positive control (5% Sodium Dodecyl Sulfate).
Under the test conditions, the test item was considered as non-irritant to skin.
- In vivo:
A key study was identified (Phycher, 2015). In this dermal irritation study performed according to the OECD Guideline No. 404, and in compliance with GLP, 3 male New Zealand White rabbits were exposed for 4 hours to a semi-occluded application of 0.5 mL of undiluted test material to the intact skin. Initially, a single animal was treated. After consideration of the cutaneous responses produced in the first treated animal, two additional animals were treated.
Slight to well - defined erythema associated with a very slight to slight oedema was noted on the treated area of all animals, 1 hour after the patch removal. All reactions were totally reversible on day 7. On the cutaneous structure, loss of litheness was noted in one animal on day 3 and dryness of the skin in all animals on day 7. The skin recovered a normal aspect on day 14 in two animals but dryness of the skin was still noted on the day 14 in one animal.
The mean scores for each animal within 3 scoring times (24, 48 and 72 h) were 2.0 / 2.0 / 1.0 for erythema and 2.0 / 1.0 / 1.0 for oedema. These effects are reversible on day 7.
Eye irritation:
A key study was identified (Phycher, 2015). In this eye irritation study performed according to the OECD guideline 405, and in compliance with GLP, 0.1 mL of undiluted test material was instilled into one eye of 3 female New Zealand White rabbits. The other eye remained untreated and served as control. The eyes were examined and the changes were observed at 1, 24, 48 and 72 h and Day 7 following treatment and graded according to the Draize method. Initially, a single animal was treated. After consideration of the ocular responses produced in the first treated animal, two additional animals were treated.
A slight redness noted 1 hour after the test item instillation and totally reversible between the 3rd and the 5th day of the test, associated with a slight to moderate chemosis, noted 1 hour after the test item instillation and totally reversible between the 2nd and the 3rd day of the test. At the corneal level, a moderate opacity, registered 24 hours after the test item instillation, in only one animal, and totally reversible the 4th day of the test.
Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 0.7, 0.3, 0.3 for cornea score; 0.0, 0.0, 0.0 for iris score; 1.0, 0.7, 0.3 for conjunctivae score and 1.0, 0.7, 0.3 for chemosis score. These effects are reversible between days 2 and 7.
Justification for classification or non-classification
Harmonized classification:
The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008 (CLP).
Self classification:
Skin irritation:
Based on the available data:
- no additional self-classification is proposed regarding skin irritation according to the CLP.
- the substance is classified in "Category 3 (mild irritant)" according to the GHS.
Eye irritation:
Based on the available data, no additional self-classification is proposed regarding eye irritation according to the CLP and to the GHS.
Respiratory irritation:
No data was available regarding respiratory irritation.
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