Registration Dossier

Diss Factsheets

Administrative data

Description of key information

In the study according to OECD 439 the test item was determined to be not irritant to skin.


The test item is not categorized for serious eye damage in the study according to OECD 437.


The test item possesses an eye irritating potential based on a study conducted according to OECD 492.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2017-03-16 to 2017-05-05
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)
Version / remarks:
23 July 2009
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Version / remarks:
July 28, 2015
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test system:
human skin model
Source species:
human
Cell type:
non-transformed keratinocytes
Cell source:
other: donors with stated consent
Justification for test system used:
Dermal irritation is generally defined as "the production of reversible inflammatory changes
in the skin". The potential for chemical induced skin irritation is an important consideration
in establishing procedures for the safe handling, packing and transport of chemicals. It is
usually determined in vivo in the Draize rabbit skin irritation test as described in OECD
guideline 404. Because systemic reactions play a minor role in modulating local skin toxicity
potential of chemicals, skin irritation potential may be predicted by in vitro systems, provided
they are sufficiently complex to mimic human skin barrier and cell reactivity. In an
international prevalidation study performed by ECVAM, the in vitro skin irritation test using
the human skin model EpiDerm™ and EpiSkin™ and measurement of cell viability by
dehydrogenase conversion of MTT into a blue formazan salt have turned out as a sufficiently
promising predictor for skin irritancy potential.
Vehicle:
unchanged (no vehicle)
Details on test system:
RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: Epi-200 SIT kits, EpiDerm™
- Tissue batch number: 25810
- Delivery date: 2017-05-03
- Date of initiation of testing: 2017-05-03 start of pre-incubation

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: 37 ± 1.5 °C for 35 min, roomt temperature for 25 min
- Temperature of post-treatment incubation: 37 ± 1.5 °C

REMOVAL OF TEST MATERIAL AND CONTROLS
- Number of washing steps: at least 15
- Observable damage in the tissue due to washing: no
- Modifications to validated SOP: no

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 1 mg/mL
- Incubation time: 3 h
- Microplate reader: Versamax® Molecular Devices, Softmax Pro, version 4.7.1
- Wavelength: 570 nm

NUMBER OF REPLICATE TISSUES: 3

CONTROL TISSUES USED IN CASE OF MTT DIRECT INTERFERENCE
No MTT interference

NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION: 1

PREDICTION MODEL / DECISION CRITERIA
- The test substance is considered to be irritant to skin if the viability is less or equal to 50 %.
- The test substance is considered to be non-irritant to skin if the viability is greater than 50 %
Control samples:
yes, concurrent negative control
yes, concurrent positive control
Amount/concentration applied:
each 30 μL
Duration of treatment / exposure:
60 min
Duration of post-treatment incubation (if applicable):
42.2 h
Number of replicates:
3
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
mean
Value:
81.8
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Remarks:
100
Positive controls validity:
valid
Remarks:
4.5
Remarks on result:
no indication of irritation
Other effects / acceptance of results:
OTHER EFFECTS:
- Visible damage on test system: no
- Direct-MTT reduction: Optical evaluation of the MTT-reducing capacity of the test item after 1 hour incubation with MTT-reagent showed weakly coloured purple oily drops. The reaction was very poor, therefore, an additional test with freeze-killed tissues was not performed, since the outcome of the test would not have been influenced importantly.
- Colour interference with MTT: no

DEMONSTRATION OF TECHNICAL PROFICIENCY: not specified

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: yes
- Acceptance criteria met for positive control: yes
- Acceptance criteria met for variability between replicate measurements: yes
- Range of historical values: positive control 4.37 +/- 21.6 % viability; negative control 1.74 +/- 9.4 Absorbance

Results




























































































































Dose
Group
Tissue
No.
Absorbance
570 nm
Well 1
Absorbance
570 nm
Well 2
Absorbance
570 nm
Well 3
Mean Absorbance
of
3 Wells
Mean-
Absorbance
of three
Wells
Blank
corrected
Mean
Absorbance
of 3
Tissues
after Blank
Correction
Rel.
Absorbance
[%]
Tissue
1, 2 + 3
Relative
Standard
Deviation
[%]
Mean Rel.
Absorbance
[% of
Negative
Control]
Blank 0.0380.0380.0360.0370    
Negative
Control
11.5671.5181.5371.5411.5041.38108.98.6100
21.4051.4071.4141.4091.37299.4
31.2941.3081.3071.3031.26691.7
Positive
Control
10.0960.1020.1010.10.0620.0624.55.14.5
20.0970.0950.0950.0960.0594.3
30.1020.1040.1010.1020.0654.7
Test Item11.2221.3111.3141.2821.2451.12990.210.881.8
21.0431.0441.0321.041.00272.6
31.1611.1721.1951.1761.13982.6
Interpretation of results:
GHS criteria not met
Conclusions:
In the study according to OECD 439 the test item was determined to be not irritant to skin.
Executive summary:

The in vitro study was performed to assess the irritation potential of the test item by means of the Human Skin Model Test.


The colourless test item did not change colour when mixed with deionised water (pre-test for colour interference). An additional test with viable tissues (without MTT addition) was not necessary. In the pre-test for direct MTT reduction a few very weak purple coloured oily drops were observed indicating a slight MTT reducing potential of the test item. Since the reaction was extremely poor, it was relinquished to perform an additional test with freezekilled tissues to determine a correction factor for calculating the true viability in the main experiment. Each three tissues of the human skin model EpiDerm™ were treated with the test item, the negative control (DPBS) or the positive control (5% SLS) for 60 minutes. After treatment with the negative control the absorbance values were well within the required range of the acceptability criterion of mean OD ≥ 0.8 and ≤ 2.8 for the 60 minutes treatment interval, thus assuring the quality of the tissues. Treatment with the positive control induced a sufficient decrease in the relative absorbance as compared to the negative control for the 60 minutes treatment interval, and thus assuring the validity of the test system. After treatment with the test item BIO4307/2 the mean relative absorbance value decreased to 81.8 % compared to the relative absorbance value of the negative control. This value is above the threshold for irritancy of ≤ 50%. Therefore, the test item is not considered to possess an irritant potential. In conclusion, it can be stated that in this study and under the experimental conditions reported, the test item is not irritant to skin.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
2017-03-27 to 2017-04-06
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
other: MatTek Corporation Protocol: EpiOcular™ Eye Irritation Test (OCL-200-EIT) for the prediction of acute ocular irritation of chemicals; for use with MatTek Corporation’s Reconstructed Human EpiOcular™ Model
Version / remarks:
29 June 2015
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 492 (Reconstructed Human Cornea-like Epithelium (RhCE) Test Method for Identifying Chemicals Not Requiring Classification and Labelling for Eye Irritation or Serious Eye Damage)
Version / remarks:
July, 2015
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
human
Details on test animals or tissues and environmental conditions:
- Justification of the test method and considerations regarding applicability
In a prevalidation study performed by Avon Products Inc. and MatTek Corporation, the in vitro eye test using the human cornea model EpiOcular™ and measurement of cell viability by dehydrogenase conversion of MTT into a blue formazan salt have turned out as a sufficiently promising predictor for eye irritancy potential.
The EpiOcular ™ Eye Irritation Test (EIT) was validated by the European Union Reference laboratory for Alternatives to Animal Testing (EURL ECVAM) and cosmetics Europe between 2008 and 2013.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent positive control
yes, concurrent negative control
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 50 μL
Duration of treatment / exposure:
30 min
Duration of post- treatment incubation (in vitro):
120 min
Number of animals or in vitro replicates:
2
Details on study design:
- Details of the test procedure used
- RhCE tissue construct used, including batch number: EpiOcular™ tissue, 23774
- Duration and temperature of exposure, post-exposure immersion and post-exposure incubation periods: standard culture conditions (37 ± 1.5 °C, 5 ± 0.5% CO2, 95% RH), only for 12 minute immersion incubation (post-soak) room temperature was used
- Indication of controls used for direct MTT-reducers and/or colouring test chemicals: Test item showed no direct MTT reducing or colouring properties. Therefore, no further controls were needed.
- Wavelength used for quantifying MTT formazan, and information on measuring device: The absorbance at 570 nm (OD570) of each well was measured with a plate reader (Versamax® Molecular Devices, 85737 Ismaning, Germany, Software Softmax Pro, version 4.7.1).
- Description of the method used to quantify MTT formazan: incubation in MTT solution for 180 min, extraction in isopropanol for ca 17 h at 2-8 °C and 2 h at RT with shaking
- Description of evaluation criteria used including the justification for the selection of the cut-off point for the prediction model:
If the test item-treated tissue viability is > 60 % relative to the negative control treated tissue viability, the test item is labeled non-irritant. If the test item-treated tissue viability is ≤ 60 % relative to negative control treated tissue viability, the test item is labeled irritant. A single test composed of at least two tissue replicates should be sufficient for a test chemical, when the result is unequivocal. However, in cases of borderline results, such as non-concordant replicate measurements and/or mean percent tissue viability equal to 60±5 %, a second test should be considered, as well as a third one in case of discordant results between the first two tests.
- Acceptability of assaya:
1) The negative control OD is > 0.8 and < 2.5,
2) The mean relative viability of the positive control is below 50% of the negative control viability.
3) The difference of viability between the two relating tissues of a single test item is < 20% in the same run (for positive and negative control tissues and tissues of test items).
Irritation parameter:
other: cell viability [%]
Run / experiment:
mean
Value:
9
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Remarks:
100
Positive controls validity:
valid
Remarks:
40
Remarks on result:
positive indication of irritation
Other effects / acceptance of results:
OTHER EFFECTS:
- Visible damage on test system: no

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: The negative control OD is > 0.8 and < 2.5 (1.922 and 2.068).
- Acceptance criteria met for positive control: The mean relative viability of the positive control is below 50 % of the negative control viability (40.0 %).
- The difference of viability between the two relating tissues of a single item is < 20 % (values between 0.6 % and 3.3 %) in the same run (for positive and negative control tissues and tissues of single test items).























































































Dose
Group
Tissue
No.
Absorbance
570 nm
Well 1
Absorbance
570 nm
Well 2
Mean Absorbance
of
2 Wells
Mean-
Absorbance
of 2 Wells
Blank
corrected
Mean
Absorbance
of 2
Tissues
after Blank
Correction
Rel.
Absorbance
[%]
Tissue
1 + 2
Absolute Value of
the Difference of
the Rel.
Absorbances [%]
Tissue 1 and 2
Mean Rel.
Absorbance
[% of
Negative
Control]
Blank 0.0380.0390.0380    
Negative
Control
11.9282.0681.9981.961.927101.73.3100
21.9221.9461.9341.89598.3
Positive
Control
10.780.8490.8150.7760.77140.30.640
20.8020.8050.8030.76539.7
Test Item10.2260.2420.2340.1950.17310.12.39
20.1920.1890.190.1527.9
Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
The test item was possesses an eye irritating potential based on a study conducted according to OECD 492.
Executive summary:

An in vitro study according to OECD 492 was performed to assess the eye irritation potential of the test item by means of the Human Cornea Model Test. The test item did not prove to be an MTT reducer in the MTT pre-test, and it did not dye water or isopropanol in the colour interference pre-test. Therefore, additional tests with freeze-killed or viable tissues did not have to be performed. Each 50 μL of the test item, the negative control (deionised water) or the positive control (methyl acetate) were applied to each of duplicate tissue for 30 minutes. After treatment with the negative control the absorbance values were well within the required acceptability criterion of OD > 0.8 and < 2.5 thus showing the quality of the tissues. Treatment with the positive control induced a decrease below 50 % compared with the negative control value in the relative absorbance thus ensuring the validity of the test system. The difference of viability between the two relating tissues was < 20 % in the same run (for test item tissues, positive and negative control tissues). Irritating effects were observed following incubation with the test item. Compared with the value of the negative control the relative mean absorption value corresponding to the viability of the tissues decreased below 60 % (9.0 %). In conclusion, it can be stated that in this study and under the experimental conditions reported, the test item possesses an eye irritating potential.

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
2017-09-15
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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:
9.12.2010
Deviations:
no
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:
July 2013
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
cattle
Strain:
not specified
Details on test animals or tissues and environmental conditions:
SOURCE OF COLLECTED EYES
- Source: AB Schlachthof GmbH & Co. KG, 63739 Aschaffenburg, Germany
- Number of animals: not specified
- Characteristics of donor animals: 9 months old
- Storage, temperature and transport conditions of ocular tissue (e.g. transport time, transport media and temperature, and other conditions): stored in HBSS containing 1% (v/v) Penicillin/Streptomycin (100 units/mL penicillin and 100 μg/mL streptomycin); in the cooled slaughter-house until transportation; transport on same morning in Styrofoam box
- Time interval prior to initiating testing: same day
- indication of any existing defects or lesions in ocular tissue samples: eyes with defects were discarded before experiment
- Indication of any antibiotics used: not specified
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent positive control
yes, concurrent negative control
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.75 mL
Duration of treatment / exposure:
10 min
Duration of post- treatment incubation (in vitro):
2 h
Number of animals or in vitro replicates:
3 each for test substance and positive and negative control
Details on study design:
SELECTION AND PREPARATION OF CORNEAS
After check of the of the eyes for defects such as vascularization, pigmentation, opacity and scratches only defect free eyes were further processed. The cornea was carefully removed from the eye using scalpel and rounded scissors. A rim of about 2 mm of tissue (sclera) was left for stability and handling of the isolated cornea. Each isolated cornea was mounted in a specially designed cornea holder according to OECD 437 437, which consists of anterior and posterior compartments, which interface with the epithelial and the endothelial sides of the cornea, respectively. The endothelial side of the cornea was positioned against the sealing ring (O-ring) of the posterior part of the holder. The cornea was gently flattened over the O-ring but stretching was avoided. The anterior part of the holder was positioned on top of the cornea and fixed in place with screws. Both compartments of the holder were filled with incubation medium. The posterior compartment was filled first to return the cornea to its natural convex position. Care was taken to assure that no air bubbles were present within the compartments. For equilibration, the corneae in the holder were incubated in a vertical position for about one hour at 32 ± 1 °C in a water-bath.

QUALITY CHECK OF THE ISOLATED CORNEAS
At the end of the incubation period, the basal opacity was determined. Each cornea with a value of the basal opacity > 7 was discarded.

REMOVAL OF TEST SUBSTANCE
- Number of washing steps after exposure period: 1 (rinsed off from the application side with saline)

- POST-EXPOSURE INCUBATION: 32 ± 1 °C for two hours in a vertical position, followed by a second opacity reading

METHODS FOR MEASURED ENDPOINTS:
- Corneal opacity: using opacitometer OP_KiT opacitometer (Electro Design, 63-Riom France)
- Corneal permeability: passage of sodium fluorescein dye measured with the aid of micro plate reader](OD490)

SCORING SYSTEM: In Vitro Irritancy Score (IVIS)

DECISION CRITERIA: The decision criteria as indicated in the TG was used.
Irritation parameter:
in vitro irritation score
Run / experiment:
mean
Value:
0.92
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Remarks:
0.53
Positive controls validity:
valid
Remarks:
70.24
Remarks on result:
no indication of irritation
Other effects / acceptance of results:
OTHER EFFECTS:
- Visible damage on test system: No

DEMONSTRATION OF TECHNICAL PROFICIENCY: not specified

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: yes
- Acceptance criteria met for positive control: yes
- Range of historical values if different from the ones specified in the test guideline: positive control mean IVIS 88.20 +/- 10.74; negative control mean IVIS 1.0 +/- 0.25

Results after 10 min treatment time
















































































Test group



Opacity value = Difference (t130-t0) of Opacity



Permeability at 490 nm (OD490)



IVIS



Mean IVIS



Proposed in vitro Irritancy Score



 



 



Mean



 



Mean



 



 



 



Negative control



-1



-0.33



0.05



0.058



-0.25



0.53



No Category



0



0.07



1.05



0



0.053



0.8



Positive control



49.33



1.323



69.18



70.24



Category 1



53.33



1.296



72.78



53.33



1.028



68.76



Test item



-0.67



0.087



0.64



0.92



No Category



0.33



0.09



1.69



-0.67



0.073



0.43



Opacity and permeability values of positive control and the test substance are shown as corrected values.

Interpretation of results:
GHS criteria not met
Conclusions:
The test item is not categorized for serious eye damage in the study according to OECD 437.
Executive summary:

The in vitro study was performed to assess the corneal damage potential of the test item by means of the BCOP assay using fresh bovine corneae.
After a first opacity measurement of the fresh bovine corneae (t0), the neat test item, the positive, and the negative controls were applied to corneae fixed in an incubation chamber in horizontal position for 10 minutes at 32 ± 1 °C. The posterior chamber contained incubation medium. After the incubation phase the test item, the positive, and the negative controls were each rinsed from the corneae. Further, the corneae were incubated for another 120 minutes at 32 ± 1 °C in a vertical position, while the anterior chamber contain incubation medium as well. Afterwards, opacity was measured a second time (t130).
After the opacity measurements permeability of the corneae was determined by measuring spectrophotometrically the transfer of sodium fluorescein after incubation in a horizontal position for 90 minutes at 32 ± 1 °C.
With the negative control (0.9% (w/v) NaCl solution in deionised water) neither an increase of opacity nor permeability of the corneae could be observed.
The positive control (2-Ethoxyethanol) showed clear opacity and distinctive permeability of the corneae corresponding to a classification as serious eye damaging (CLP/EPA/GHS (Cat 1)).
Relative to the negative control, the test item did not cause an increase of the corneal opacity or permeability. The calculated mean in vitro irritancy score was 0.92. According to OECD 437 the test item is not categorized (GHS).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation


The in vitro study was performed to assess the irritation potential of the test item by means of the Human Skin Model Test. The colourless test item did not change colour when mixed with deionised water (pre-test for colour interference). An additional test with viable tissues (without MTT addition) was not necessary. In the pre-test for direct MTT reduction a few very weak purple coloured oily drops were observed indicating a slight MTT reducing potential of the test item. Since the reaction was extremely poor, it was relinquished to perform an additional test with freezekilled tissues to determine a correction factor for calculating the true viability in the main experiment. Each three tissues of the human skin model EpiDerm™ were treated with the test item, the negative control (DPBS) or the positive control (5% SLS) for 60 minutes. After treatment with the negative control the absorbance values were well within the required range of the acceptability criterion of mean OD ≥ 0.8 and ≤ 2.8 for the 60 minutes treatment interval, thus assuring the quality of the tissues. Treatment with the positive control induced a sufficient decrease in the relative absorbance as compared to the negative control for the 60 minutes treatment interval, and thus assuring the validity of the test system. After treatment with the test item BIO4307/2 the mean relative absorbance value decreased to 81.8 % compared to the relative absorbance value of the negative control. This value is above the threshold for irritancy of ≤ 50%. Therefore, the test item is not considered to possess an irritant potential. In conclusion, it can be stated that in this study and under the experimental conditions reported, the test item is not irritant to skin.


 


Eye irritation


A weight of evidence approach was used to determine the potential of the test item to induce eye irritation or seriouse eye damage. Therefore, studies according to OECD 492 and 437 were conduced.


 


An in vitro study according to OECD 492 was performed to assess the eye irritation potential of the test item by means of the Human Cornea Model Test. The test item did not prove to be an MTT reducer in the MTT pre-test, and it did not dye water or isopropanol in the colour interference pre-test. Therefore, additional tests with freeze-killed or viable tissues did not have to be performed. Each 50 μL of the test item, the negative control (deionised water) or the positive control (methyl acetate) were applied to each of duplicate tissue for 30 minutes. After treatment with the negative control the absorbance values were well within the required acceptability criterion of OD > 0.8 and < 2.5 thus showing the quality of the tissues. Treatment with the positive control induced a decrease below 50 % compared with the negative control value in the relative absorbance thus ensuring the validity of the test system. The difference of viability between the two relating tissues was < 20 % in the same run (for test item tissues, positive and negative control tissues). Irritating effects were observed following incubation with the test item. Compared with the value of the negative control the relative mean absorption value corresponding to the viability of the tissues decreased below 60 % (9.0 %). In conclusion, it can be stated that in this study and under the experimental conditions reported, the test item possesses an eye irritating potential.


 


The in vitro study was performed to assess the corneal damage potential of the test item by means of the BCOP assay using fresh bovine corneae.
After a first opacity measurement of the fresh bovine corneae (t0), the neat test item, the positive, and the negative controls were applied to corneae fixed in an incubation chamber in horizontal position for 10 minutes at 32 ± 1 °C. The posterior chamber contained incubation medium. After the incubation phase the test item, the positive, and the negative controls were each rinsed from the corneae. Further, the corneae were incubated for another 120 minutes at 32 ± 1 °C in a vertical position, while the anterior chamber contain incubation medium as well. Afterwards, opacity was measured a second time (t130).
After the opacity measurements permeability of the corneae was determined by measuring spectrophotometrically the transfer of sodium fluorescein after incubation in a horizontal position for 90 minutes at 32 ± 1 °C.
With the negative control (0.9% (w/v) NaCl solution in deionised water) neither an increase of opacity nor permeability of the corneae could be observed.
The positive control (2-Ethoxyethanol) showed clear opacity and distinctive permeability of the corneae corresponding to a classification as serious eye damaging (CLP/EPA/GHS (Cat 1)).
Relative to the negative control, the test item did not cause an increase of the corneal opacity or permeability. The calculated mean in vitro irritancy score was 0.92. According to OECD 437 the test item is not categorized (GHS).


 


The weight of evidence shows that the test item possesses eye irritation potential (OECD 492) but no potential do induce seriouse eye damage (OECD 437).

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008


Based on available data on skin irritation/corrosion, the test item is not classified according to Regulation (EC) No 1272/2008 (CLP), as amended for the fifteenth time in Regulation (EU) No 2020/1182.


Based on available data on eye irritation/serious eye damage, the test item is classified as causing eye irritation (Cat. 2, H319: Causes serious eye irritation) according to Regulation (EC) No 1272/2008 (CLP), as amended for the fourteenth time in Regulation (EU) 2020/217.