Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin corrosion: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
13 February 2017 - 17 February 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 431 (In Vitro Skin Corrosion: Reconstructed Human Epidermis (RHE) Test Method)
Version / remarks:
29 July 2016
Deviations:
no
Qualifier:
according to
Guideline:
other: EU method B.40 BIS (In Vitro Skin corrosion: Human Skin Model Test)
Version / remarks:
31 May 2008
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
Purity correction factor: 1.14
Stability at higher temperatures: stable at a maximum temperature of 60°C for a maximum duration of 30 minutes
Test system:
human skin model
Source species:
human
Cell type:
non-transformed keratinocytes
Cell source:
skin obtained from plastic surgery from multiple donors
Details on animal used as source of test system:
EpiDerm™ Reconstructed Human Epidermis (Lot no.: 24982 kit H and I)
- All cells used to produce Eipderm™ are purchased or derived from tissue obtained by MatTek Corporation from acredited institutions.
- Cells are screened for potential biological contaminants (HIV-1, Hepatitis B, Hepatitis C, bacteria, yeast and fungi)
Justification for test system used:
Recommended test system in international guidelines (OECD and EC).
Details on test system:
RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: EpiDerm Skin Model (EPI-200)
- Tissue lot number: 24982 kit H and I
- Surface: 0.6 cm^2
- The model consists of keratinocytes which have been cultured to form a multilayered, highly differentiated model of the human epidermis.

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: All incubations, with the exception of the test item incubation of 3 minutes at room temperature, were carried out in a controlled environment at 37.0 ± 1.0°C (actual range: 36.6 - 37.0°C)

REMOVAL OF TEST MATERIAL AND CONTROLS
- After the exposure period, the tissues were washed with phosphate buffered saline to remove residual test item.

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration: 1 mg/mL
- Incubation time: 3 h
- Spectrophotometer: TECAN Infinite® M200 Pro Plate Reader
- Wavelength: 570 nm

NUMBER OF REPLICATE TISSUES: 2 replicates per exposure duration (4 replicates per test item), one negative control, one positive contol.

ACCEPTANCE OF RESULTS:
The in vitro skin corrosion test is considered acceptable if it meets the following criteria:
a) The absolute mean OD570 of the two tissues of the negative control should reasonably be within the acceptance limits of OECD 431 (lower limite ≥0.8 and upper limit ≤2.8)
b) The mean relative tissue viability following 1-hour exposue to the positive control should be <15%
c) In the range 20-100% viability, the Coefficient of Variation (CV) between tissue replicates should be ≤30%.

DECISION CRITERIA: see table 1
Control samples:
yes, concurrent negative control
yes, concurrent positive control
yes, concurrent MTT non-specific colour control
other: concurrent control for MTT reduction by test item
Amount/concentration applied:
Excess amount of the paste, spread directly on top of skin moistened with 25 µL Milli-Q water
Duration of treatment / exposure:
3-minute and 1-hour
Duration of post-treatment incubation (if applicable):
none
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
3-minute exposure
Value:
107
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Remarks:
(100%)
Positive controls validity:
valid
Remarks:
(29%)
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
1-hour exposure
Value:
90
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Remarks:
(100%)
Positive controls validity:
valid
Remarks:
(9%)
Other effects / acceptance of results:
- Because the mean relative tissue viability for the test item was not below 50% after 3 minutes treatment and not below 15% after 1 hour treatment, the test item is considered to be non corrosive.

- OTHER EFFECTS:
- Direct-MTT reduction: No
- Colour interference with MTT: No

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: Yes
- Acceptance criteria met for positive control: Yes, mean relative tissue viability following 1-hour exposure was 9%.
- In the range of 20 - 100% viability the Coefficient of Variation between tissue replicates was ≤12% for the test item and negative control. For the positive control, the Coefficient of Variation between tissue replicates at the 3-minute exposure was 39%. Since both individual tissues of the positive control were clearly positive it was concluded that the test system functioned properly.

Table 2 shows the results of individual OD measurements at 570 nm.

Table 2 Individual OD measurements at 570 nm.

 

3-minute application (OD570)

1-hour application (OD570)

 

A

B

A

B

Negative control

Measurement 1

Measurement 2

Measurement 3

1.4908

1.4052

1.4427

1.4308

1.3742

1.4020

 

1.7312

1.7305

1.6864

1.5932

1.5681

1.5657

X-19924

Measurement 1

Measurement 2

Measurement 3

 

1.6368

1.6057

1.5798

 

1.4898

1.3770

1.4145

 

1.4855

1.4863

1.4874

 

1.4870

1.4816

1.5166

Positive control

Measurement 1

Measurement 2

Measurement 3

 

0.5413

0.5453

0.5385

 

0.3585

0.3446

0.3422

 

0.1999

0.2067

0.2032

 

0.1843

0.1793

0.1789

Interpretation of results:
GHS criteria not met
Conclusions:
An in vitro skin corrosion test was conducted with X-19924 according to OECD 431 guideline and GLP principles. It is concluded that this test is valid and that X-19924 is not corrosive in the in vitro skin corrosion test under the experimental conditions described in this report.

NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
5th October 2017- 8th October 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Male test animals approximately ten to twelve weeks old were used for this study. The rabbits were obtained from Kuiper Rabbitry, Gary, Indiana. The rabbits weighed from 2.21 to 2.57 kilograms at the start of the study and were individually housed in stainless steel cages in a temperature (20 ± 3° C), humidity (30-70%), and (12 hour/cycle) light controlled room. Each rabbit was assigned a test animal number which appeared as an ear tag and also appeared on a cage card visible on the front of each cage. The rabbits were nulliparous and non-pregnant. The rabbits were maintained according to the recommendations contained in the National Academy Press 2011: "Guide for the Care and Use of Laboratory Animals". They were conditioned for at least five days prior to study initiation. Purina Laboratory Rabbit Chow and water were available ad libitum. All animals used for this study were considered to be in good health at study initiation.
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Amount / concentration applied:
0.5ml
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3 animals
Details on study design:
Electric clippers were used to remove the hair from the left side of the trunk, from the midline of the back to the abdomen. The following day a 0.5 ml aliquot of the test material, which was slightly moistened w/water to assure good skin contact, was then applied to an area approximately 6 square centimeters on the side of the test animal. The application site is located approximately 5-7 centimeters down from the backbone. The test substance was then covered with a 2.5 cm² - 2 layer gauze patch held in place with non-irritating Kendall Curity Standard Porous Tape and the patch was then covered with a semi-occlusive plastic overwrap secured in place with Kendall Curity Standard Porous Tape for the duration of the exposure period. At the end of the 4 hour contact period, excess material was removed from the site; the site being observed and scored. Dermal irritation readings for erythema and edema were performed approximately 4.5, 24, 48 and 72
hours after treatment.
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
0
Reversibility:
other: No erythema was observed
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 0
Max. score:
0
Reversibility:
other: No erythema observed
Interpretation of results:
GHS criteria not met
Conclusions:
Following exposure to test substance, on the skin of 3 animals, the application sites were graded for indication of skin reactions at 4.5, 24, 48 and 72 hours after test substance application.
There were no skin irritation reactions in any of the test subjects. Therefore, in accordance with the criteria set forth itn the CLP guidiance, the test substance will not be classififed for skin irrtaition.
Executive summary:

The hair from the left side of the trunk ( from the midline of the back to the abdomen.) of 3 Male New Zealand White Rabbits were removed using electri clippers exposed to the test substance for 4 hours. O.5ml of test substance moistened with water to ensure good skin contact was applied to an area approximately 6 square centimeters on the side of the test animal. The application site is located approximately 5-7 centimeters down from the backbone. The test substance was then covered with a 2.5 cm² - 2 layer gauze patch held in place with non-irritating Kendall Curity Standard Porous Tape and the patch was then covered with a semi-occlusive plastic overwrap secured in place with Kendall Curity Standard Porous Tape for the duration of the exposure period. At the end of the 4 hour contact period, excess material was removed from the site; the site being observed and scored.

The application sites were graded for indication of skin reactions at 4.5, 24, 48 and 72 hours after test substance application. There were no skin irritation reactions in any of the test subjects. Therefore, in accordance with the criteria set forth itn the CLP guidiance, the test substance will not be classififed for skin irritation.

NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.

Endpoint:
skin corrosion: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Justification for type of information:
Invivo study was conducted for R n D purposes hence an invtro skin irritation study does not need to be conducted.
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
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Justification for type of information:
In vitro study will not be necessary due to adequate data from in vivo eye irritation study conducted for R n D purposes.
Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
07 February 2017 - 28 February 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
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:
26 July 2013
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
- Correction factor for purity: 1.138; this correction factor was not applied in this study since a correction factor is not applicable to the BCOP test.
- Stability at higher temperatures: stable for a maximum of 30 minutes at a maximum temperature of 60ºC
Species:
cattle
Details on test animals or tissues and environmental conditions:
SOURCE OF COLLECTED EYES
- Source: young cattle, obtained from the slaughterhouse Vitelco, 's-Hertogenbosch, The Netherlands.
- Storage, temperature and transport conditions of ocular tissue: eyes were excised by a slaughterhouse employee as soon as possible after slaughter. Subsequently, eyes were collected an transported in physiological saline in a suitable container under cooled conditions.
- The eyes were checked for unacceptable defects and those exhibiting defects were discarded.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent positive control
yes, concurrent negative control
Amount / concentration applied:
TEST MATERIAL
- Amount applied: excessive amount to cover the complete cornea

NEGATIVE CONTROL: 750 µL

POSITIVE CONTROL: 750 µL
Duration of treatment / exposure:
10 ± 1 minutes
Duration of post- treatment incubation (in vitro):
120 ±10 minutes in cMEM for opacity measurements and subsequently 90 ±5 minutes in sodium-fluorescein for permeability determinations
Number of animals or in vitro replicates:
3 for the negative control, the positive control and the treatment group each
Since the first experiment was inconclusive, a second experiment was performed.
Details on study design:
SELECTION AND PREPARATION OF CORNEAS: The eyes were checked for unacceptable defects and those exhibiting defects were discarded. The isolated corneas were stored in a petri dish with cMEM containing 1% (v/v) L-glutamine and 1% (v/v) Foetal Bovine Serum. The isolated corneas were mounted in a corneal holder (one cornea per holder) with the endothelial side against the O-ring of the posterior half of the holder. The anterior half of the holder was positioned on top of the cornea and tightened with screws. The compartments of the corneal holder were filled with cMEM of 32 °C ± 1 °C. The corneas were incubated for the minimum of 1 hour at 32 °C ± 1 °C

TREATMENT METHOD: The medium from the anterior compartment was removed and 750 µL of either the negative control, positive control or an excessive amount of test item was introduced onto the epithelium of the cornea. The holders were slightly rotated, with the corneas maintained in a horizontal position, to ensure uniform distribution of the control or the test item over the entire cornea. Corneas were incubated in a horizontal position for 10 ± 1 minutes at 25.0 °C. In the repeat of the second experiment, corneas treated with negative and positive control were incubated in a horizontal position for 10 ± 1 minutes at 32.0 °C ± 1 °C and the test item was incubated in a horizontal position for 10 ± 1 minutes at 28.5°C.

REMOVAL OF TEST SUBSTANCE
- Number of washing steps after exposure period: After the incubation the solutions were removed and the epithelium was washed with MEM with phenol red (Earle’s Minimum Essential Medium, Life Technologies) and thereafter with cMEM.

- POST-EXPOSURE INCUBATION: 120 ±10 minutes in cMEM for opacity measurements and subsequently 90 ±5 minutes in sodium-fluorescein for permeability determinations

METHODS FOR MEASURED ENDPOINTS:
- Corneal opacity: opacity meter (OP-KIT)
- Corneal permeability: passage of sodium fluorescein dye measured with the aid of a microtiter plate reader (TECAN Infinite® M200 Pro Plate Reader, OD490). OD490 values of less than 1.500 were used in the permeability calculation.
- Other: possible pH effects of the test substance on the corneas were recorded.

SCORING SYSTEM: In Vitro Irritancy Score (IVIS)

DECISION CRITERIA (see table 1):
A test substance that induces an IVIS ≤ 3 is not classified for eye irritancy (UN GHS: no category);
A test substance that induces IVIS >55 is defined as a corrosive or severe irritant (UN GHS: category 1);
For a test substance that induces an IVIS >3 and ≤55, no prediction on irritant potency can be made.
Irritation parameter:
in vitro irritation score
Run / experiment:
First experiment; mean of 3 replicates
Value:
3.2
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Remarks:
IVIS: 0.0 - 1.9
Positive controls validity:
valid
Remarks:
IVIS: 34.0 - 62.2
Remarks on result:
other: results were spread over 2 categories
Irritation parameter:
in vitro irritation score
Run / experiment:
Second experiment; mean of 3 replicates
Value:
2.7
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Remarks:
IVIS: -1.2 - -0.5
Positive controls validity:
valid
Remarks:
IVIS: 48.2-82.1
Remarks on result:
other: results were spread over 2 categories
Other effects / acceptance of results:
FIRST EXPERIMENT:
- The corneas treated with the test substance showed opacity values between 1.3 and 3.8.
- Permeability values were ranging from 0.023 to 0.060.
- IVIS were 1.8, 3.0 and 4.8 (n=3).

Since the results of the first experiment were spread over 2 categories, the test was inconclussive and a second experiment was performed.

SECOND EXPERIMENT:
- The corneas treated with the test substance showed opacity values between 0.2 and 4.4.
- Permeability values were ranging from 0.003 to 0.040.
- IVIS were 0.9, 2.1 and 5.0 (n=3).

Since the individual in vitro irritancy scores were spread over 2 categories, the test was inconclusive.

OTHER EFFECTS:
- No pH effect of the test item was observed on the rinsing medium in both experiments.

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: yes, results were within historical range (IVIS ranging from 0.0 to 1.9 in the first experiment and ranging from 1.2 to -0.5 in the second experiment). However, in the first experiment, one of the negative control eyes was excluded from the analysis since the IVIS was >3. Since the other 2 eyes completely met the criteria and test item results were not influenced by this result this does not affect the study outcome.
- Acceptance criteria met for positive control: yes, results were within historical range (IVIS ranging from 34 to 62 in the first experiment and ranging from 48 to 82 in the second experiment). In both experiments, the corneas treated with the positive control item were turbid after the 10 minutes of treatment.

Table 2 Historical Control Data for the BCOP Studies

 

Negative control

Positive control

 

Opacity

Permeability

In vitro Irritancy Score

In vitro Irritancy Score

Range

-2.9 – 3.0

-0.016 – 0.042

-2.8 – 3.0

35.8-77.0

Mean

0.20

0.01

0.32

57.55

SD

1.02

0.01

1.10

12.12

n

63

59

57

38

SD = Standard deviation

n = Number of observations

The above mentioned historical control data range of the controls were obtained by collecting all data over the period of February 2015 to November 2016.

Interpretation of results:
study cannot be used for classification
Conclusions:
Based on the results of a Bovine Corneal Opacity and Permeability test (BCOP) performed according to OECD guideline 437 and GLP principles, no conclusion can be drawn for the classification of X-19924 for eye irritation. The IVIS were spread over 2 categories in a first and in a second experiment (1.8, 3.0, 4.8 and 0.9, 2.1, 5.0, respectively).

NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
30th May 2017 - 7th June 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
The study was conduceted with Female New Zealand White Rabbits ten to twelve weeks old. The rabbit were obtained from Kuiper Rabbitry, Gary, Indiana. The rabbits weighed from 3.42 to 3.78 kilograms at the start of the study and were individually housed in stainless steel cages in a temperature (63-73°F), humidity (30-70%), and light controlled room. Each rabbit was assigned a test animal number which appeared on a cage card visible on the front of each cage. The females were nulliparous and non-pregnant. The rabbits were maintained according to the recommendations contained in the National Academy Press 2011: "Guide for the Care and Use of Laboratory Animals". They were conditioned for at least five days prior to study initiation. Purina Rabbit chow and water were available ad libitum. All animals used for this study were considered to be in good health at the study initiation
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
0.1ml 100% concentration
Duration of treatment / exposure:
Three animals were dosed by instilling 0.1 ml of the test article into one eye and then holding the eye lids together for one second to prevent loss of the material. The contralateral eye served as the untreated control for each rabbit.
Observation period (in vivo):
168 hours
Number of animals or in vitro replicates:
3 animals
Details on study design:
The animals were prepared 24 hours before the start of the stud, both eyes of the experimental animals were examined for pre-existing ocular lesions. Only those animals with no pre-existing ocular lesions were used for test purposes. Five minutes prior to dosing, the eyes were anesthetized with Tetracaine HCL solution. Three animals were dosed by instilling 0.1 ml of the test article into one eye and then holding the eye lids together for one second to prevent loss of the material. The contralateral eye served as the untreated control for each rabbit.The other eye of each animal served as the control.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0.76
Max. score:
4
Reversibility:
fully reversible
Remarks:
within 7 days
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.43
Max. score:
2
Reversibility:
fully reversible
Remarks:
within 7 days
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
mean
Time point:
24/48/72 h
Score:
1.62
Max. score:
3
Reversibility:
fully reversible
Remarks:
within 7 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0.96
Max. score:
4
Reversibility:
fully reversible
Remarks:
within 7 days
Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Following exposure to the test substance when administered into one eye of each of three albino rabbits, the eyes were observed and scored at 1, 24, 48, 72 and 168 hours. 2 animals had a Cornea opacitiy mean scoe of ≥1 , 1 animal had Iris mean score ≥1 , but no animal had mean score ≥2 for Redness and Chemosis. However, the observed effects were fully revised within 7 days. Therefore, in accordance witth the CLP guidiances, the test substance is classified as an eye irritant category 2, H319.
Executive summary:

The eye irritating potential of the test substance was conducted in accordance to the OECD 405 guideline. 3 Female New Zealand White Rabbits ten to twelve weeks old were used for this study. 24 hours before the start of the study both eyes of the experimental animals were examined for pre-existing ocular lesions. Only those animals with no pre-existing ocular lesions were used for test purposes. Five minutes prior to dosing, the eyes were anesthetized with Tetracaine HCL solution. Three animals were dosed by instilling 0.1 ml of the test article into one eye and then holding the eye lids together for one second to prevent loss of the material. The contralateral eye served as the untreated control for each rabbit.

The eyes were examined at 1, 24, 48, 72 and 168 hours after treatment.. 2% sodium fluorescein and ultraviolet light provided via a Spectroline, Model Q-12, Long Wave UV-365nm, 10X Magnifier, were employed to reveal possible corneal injury commencing with the 24 hour observation. Following exposure to the test substance when administered into one eye of each of three albino rabbits, there was moderate irritation observed in all of the test subjects. The eyes were observed and scored at 1, 24, 48, 72 and 168 hours. 2 animals had a Cornea opacitiy mean scoe of ≥1 ,  1 animal had Iris mean score  ≥1 , but no animal had mean score ≥2 for Redness and Chemosis. However, the observed  effects were fully revised within 7 days. Therefore, in accordance witth the CLP guidiances, the test substance is classified as an eye irritant category 2, H319.

NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Justification for classification or non-classification

Following exposure to test substance, on the skin of 3 animals, the application sites were graded for indication of skin reactions at 4.5, 24, 48 and 72 hours after test substance application. There were no skin irritation reactions in any of the test subjects. Therefore, in accordance with the criteria set forth itn the CLP guidiance, the test substance will not be classififed for skin irrtaition.

Following exposure to the test substance when administered into one eye of each of three albino rabbits,  the eyes were observed and scored at 1, 24, 48, 72 and 168 hours. 2 animals had a Cornea opacitiy mean scoe of ≥1  ,  1 animal had Iris mean score  ≥1 , but no animal had mean score  ≥2 for Redness and Chemosis. However, the observed  effects were fully revised within 7 days. Therefore, in accordance witth the CLP guidiances, the test substance is classified as an eye irritant category 2, H319.