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Diss Factsheets

Administrative data

Description of key information

Skin irritation: Not irritating to the skin (Draize Test, K, Rel.2)

Eye irritation: Not irritating to the eyes based on a Weight-of-Evidence approach (Draize Test, Rel.2 and OECD 437, Rel.1)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Remarks:
purity of test substance; acclimation period, details on test animals and housing/feeding conditions not reported; 24 h exposure period, occlusive dressing used, observation at 24 and 72 h only, full reversibility not observed
Qualifier:
no guideline followed
Principles of method if other than guideline:
In a dermal irritation study, test substance was dermally applied on the intact or abraded side surface of 6 New Zealand White rabbits. Test sites were covered with an occlusive dressing for 24 h. Skin irritation was assessed and scored according to the Draize scale at 24 and 72 h after the removal of the patch.
GLP compliance:
no
Remarks:
pre-GLP
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
occlusive
Preparation of test site:
other: abraded and unabraded
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
Duration of treatment / exposure:
24 hours
Observation period:
24 and 72 hours after application of test substance
Number of animals:
6 animals
Details on study design:
TEST SITE
- Area of exposure: The back of each rabbits were clipped free of hair 24 hour before application of the test substance. Two sites were abraded and two were unabraded. The test substance was applied to the test site.
- Type of wrap if used: The test sites were covered with a gauze pad and the entire back was overwrapped with rubber dam.

REMOVAL OF TEST SUBSTANCE
- 24 hours later, the wraps were removed and excess test substance was removed and each test site was scored for erythema and edema.

OBSERVATION TIME POINTS
24 and 72 hours after application of test substance

SCORING SYSTEM:
- Method of calculation: Draize method
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24h and 72h
Score:
0.04
Remarks on result:
other: primary irritation score
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not determinable
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not determinable
Irritant / corrosive response data:
Test substance caused a minimum amount of edema in one of the six treated rabbits at the 24-hour reading only. The total primary irritation score was 0.04.
Other effects:
None

None

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the test substance was non-irritating to skin of rabbits, therefore it is not classified according to the annex I of the Regulation EC No. 1272/2008 (CLP) and to the GHS.
Executive summary:

In a dermal irritation study, 0.5 g of test substance was dermally applied on the intact or abraded side surface of 6 New Zealand White rabbits. Test sites were covered with an occlusive dressing for 24 h. Skin irritation was assessed and scored according to the Draize scale at 24 and 72 h after the removal of the patch.

 

Test substance caused a minimum amount of edema in one of the six treated rabbits at the 24-hour reading only. The total primary irritation score was 0.04.

Reversibility was not assessed.

 

Under the test conditions, the test substance was non-irritating to skin of rabbits, therefore it is not classified 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 skin irritation endpoint.

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

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Remarks:
purity of test substance; acclimation period, details on test animals and housing/feeding conditions not reported; eyes were washed
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
purity of test substance; acclimation period, details on test animals and housing/feeding conditions not reported; eyes were washed
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Remarks:
pre-GLP
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated right eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g
Duration of treatment / exposure:
Test substance was washed from the eye of six rabbits (30 seconds after instillation in three rabbits; 5 minutes after instillation in another three rabbits); and no washing was done in three rabbits.
Observation period (in vivo):
1, 4, 24, 48, 72, 96 hours and 7 days after instillation of test substance
Number of animals or in vitro replicates:
9 animals
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Test substance was washed from the eye of six rabbits (30 seconds after instillation in three rabbits; 5 minutes after instillation in another three rabbits); and no washing was done in three rabbits.

SCORING SYSTEM: Draize method
Remarks on result:
other: See "Any other information on results incl. tables"
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not determinable
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not determinable
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not determinable
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Remarks on result:
not determinable
Irritant / corrosive response data:
Irritation was observed in conjunctival and iris tissues only. All three rabbits in the no-wash and 5 minute wash groups showed circumcorneal injection around the iris at the 1-hour reading. This condition persisted for 3 days in the no-wash group. Occasional circumcorneal injection responses were noted in individual rabbits at all treatment levels, but all effects involving the iris had disappeared by day 4 after treatment.
Conjunctival responses were observed at all treatment levels and generally involved mild redness, chemosis, and discharge. The treated eye of all rabbits in the 30-second wash group had returned to normal within 24 hours, whereas the treated eye of rabbits in the 5-minute wash group did not completely clear until day 4, and the no-wash group was not judged normal in response until day 7. Overall, the degree of eye irritation caused by test substance was mild but transitory.

Table 7.3.2/1: Summary of eye irritation responses in rabbits treated with test substance (three rabbits per wash condition)

 

Tissues graded*

Average Irritancy Score

Hours

Days

1

4

1

2

3

4

7

30 Seconds washing

Cornea

0

0

0

0

0

 

 

Iris

0

1.7

0

0

0

 

 

Conjunctivae

5.3

4.0

0

0

0

 

 

5 minutes washing

Cornea

0

0

0

0

0

 

 

Iris

5.0

0

0

1.7

0

 

 

Conjunctivae

1.7

2.7

2.0

2.0

0.7

0

 

No wash

Cornea

0

0

0

0

0

0

0

Iris

5.0

1.7

1.7

1.7

1.7

0

0

Conjunctivae

4.0

2.7

1.3

0.7

0.7

0.7

0

 

*Maximum corneal response: 80; Maximum iris response: 10; Maximum conjunctivae response: 20

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the test substance was mild but transitory irritant to the eyes of rabbits.
Executive summary:

In an eye irritation study, 0.1 g of test substance was instilled into the left eye of 9 New Zealand White rabbits while the right eye remained untreated and served as control. Test substance was washed from the eye of six rabbits (30 seconds after instillation in three rabbits; 5 minutes after instillation in another three rabbits); and no washing was done in three rabbits. Animals were observed at 1, 4, 24, 48, 72, 96 h and 7 days after instillation of test substance.

Irritation was observed in conjunctival and iris tissues only. All three rabbits in the no-wash and 5 minute wash groups showed circumcorneal injection around the iris at the 1-hour reading. This condition persisted for 3 days in the no-wash group. Occasional circumcorneal injection responses were noted in individual rabbits at all treatment levels, but all effects involving the iris had disappeared by day 4 after treatment. Conjunctival responses were observed at all treatment levels and generally involved mild redness, chemosis, and discharge. The treated eye of all rabbits in the 30-second wash group had returned to normal within 24 hours, whereas the treated eye of rabbits in the 5-minute wash group did not completely clear until day 4, and the no-wash group was not judged normal in response until day 7. Overall, the degree of eye irritation caused by test substance was mild but transitory.

Under the test conditions, the test substance was mild but transitory irritant to the eyes of rabbits.

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
24 August 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying i) Chemicals Inducing Serious Eye Damage and ii) Chemicals Not Requiring Classification for Eye Irritation or Serious Eye Damage)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
cattle
Strain:
other: Bos Taurus
Details on test animals or tissues and environmental conditions:
SOURCE OF COLLECTED EYES
- Source: Bovine eyes were obtained from freshly slaughtered cattle at the abattoir EVA, Saint Pierre sur Dives, France.
- Number of animals: Not reported
- Characteristics of donor animals: Bovine cattle were up to 12 months old (typically, 5 to 8 months old)
- Storage, temperature and transport conditions of ocular tissue: The eyes were transported to CiToxLAB France at ambient temperature, immerged in buffered Hanks medium containing an antibiotic [Hank’s Balanced Salts Solution (HBSS) plus penicillin/streptomycin (100 units/100 µg/mL final)]. A container with smooth internal surfaces was used for the transport to avoid damage to the corneas.
- Time interval prior to initiating testing: The corneas were used immediately after preparation.
- indication of any existing defects or lesions in ocular tissue samples: a careful macroscopic examination was performed on all eyes to detect the presence of any defects (opacity, scratches, pigmentation, etc). Any eyes with defects were discarded. The examination was performed under a lamp, using HBSS in order to keep the eyes moistened and shiny. Particular attention was paid to the corneas and the eyes were swiveled in order to observe the fringe areas and any scratches directly under the light.
- Indication of any antibiotics used: HBSS containing penicillin/streptomycin (100 units/100 µg/mL final)
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent positive control
yes, concurrent negative control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 750 mg (± 75 mg)
- Concentration: not applicable (solid, neat)
Duration of treatment / exposure:
4 hours (± 5 minutes) at 32 °C, vertically (cornea positioned horizontally with the treated side uppermost)
Number of animals or in vitro replicates:
3 corneas per group
Details on study design:
SELECTION AND PREPARATION OF CORNEAS
- the tissues surrounding the eyeball were carefully pulled away and the cornea, surrounded by approximately 2 to 3 mm of sclera, was dissected out. The isolated corneas were stored in HBSS until all corneas had been prepared.
- the corneas were washed for 15 minutes, three times, in HBSS plus penicillin/streptomycin (100 units/100 µg/mL final) at room temperature. The corneas were used immediately.
- The corneas were mounted in the corneal holders with the endothelial side against the O-ring of the posterior chamber. Each cornea was identified with the corresponding holder number.

QUALITY CHECK OF THE ISOLATED CORNEAS: The corneas were carefully examined macroscopically before their assembly in the holders, in order to detect the presence of any defects. Any corneas with defects were discarded.

NUMBER OF REPLICATES: 3 corneas per group

NEGATIVE CONTROL USED: 0.9% Sodium Chloride (0.9% NaCl)

POSITIVE CONTROL USED: 20% imidazole solution in 0.9% NaCl (w/v)

PRE-INCUBATION: Both chambers of the corneal holder were filled to overflowing with MEM culture media supplemented with 1% fetal bovine serum plus penicillin/streptomycin (cMEM) at room temperature. The posterior chamber was always filled first to maintain the natural concave shape of the cornea.
After making sure that no air bubbles were present within the holder, it was immersed in a water bath, horizontally (cornea positioned vertically), up to approximately three quarters of its height. The holders were pre incubated for 1 hour and 5 minutes (± 5 minutes) at +32°C (± 1°C).

At the end of the pre-incubation period, the medium was removed from both chambers of the holder using a metal gavage tube attached to a vacuum pump to ensure complete evacuation. They were refilled with fresh cMEM without phenol red (previously heated to +32°C), starting with the posterior chamber and taking care that no air bubbles were present. The chambers were re-sealed and the corneas were examined macroscopically through the holder to detect the presence of any defects. Then, the opacity of the cornea was measured to obtain OPT0.
Corneas that showed any macroscopic defect or an OPT0 value over 7 were discarded.

APPLICATION DOSE AND EXPOSURE TIME:
- The medium of the anterior chamber was removed and each item (i.e. test item, positive and negative controls) was applied onto the epithelium of the cornea.
- Since the test item was a solid and was tested neat, 750 mg (± 75 mg) of the test item was applied to each cornea using the open-chamber treatment method as follows: the window locking ring and glass window of the anterior chamber were removed. The test item was gently applied onto the epithelium of the cornea, as uniformly as possible in order to ensure that it covers the whole epithelial surface. The glass window of the anterior chamber was then replaced (without the window-locking ring).
- 750 µL (± 8 µL) of negative or positive control applied for each cornea using the closed-chamber treatment method.
- The treatment time of each series of three corneas was carefully measured with a chronometer, starting from the beginning of treatment of the first cornea of each series. Then each further operation (rinsing, measurement, etc.) was carried out in the same order for the three corneas of each series.
- After application of the items, the holders were incubated vertically during 4 hours (± 5 minutes) (cornea positioned horizontally with the treated side uppermost) in a water bath at +32°C (± 1°C), for the selected treatment time.

TREATMENT METHOD: open chamber for test item / closed-chamber for negative and positive controls.

REMOVAL OF TEST SUBSTANCE
Number of washing steps after exposure period: 3
-residual test item adhering to the walls of the anterior chamber was removed using a pipette of heated cMEM (32°C),
-the corneas were rinsed three times with pre-warmed cMEM containing phenol red (i.e. until the test item had been completely removed from the chamber or until the phenol red was not discoloured). Then, the corneas were finally rinsed with pre-warmed cMEM without phenol red.
- The rinsing efficiency was visually confirmed by observing the transparency and the colour changing of the rinsing medium (containing phenol red). Despite the rinsing performed, residual amounts test item were still noted over the three test item-treated corneas. Moreover, the quantity of these residues was noted significantly higher on the third cornea treated with the test item (i.e. holder n° 82).
- The anterior chamber was refilled with fresh pre-warmed cMEM without phenol red. The front cover was replaced. Care was taken to make sure that no air bubbles were present within the holders (by ensuring that each chamber was filled to overflowing with pre-warmed cMEM).
- Following the 4-hour treatment and the rinsing step, the medium of both chambers was renewed with pre warmed cMEM (+32°C) and the second opacity measurement (OPT2) was performed directly.

METHODS FOR MEASURED ENDPOINTS:
- Corneal opacity:
An opacitometer was used to measure light transmission (i.e. the level of opacity) through the center of each mounted cornea. A numerical opacity measurement (arbitrary unit) was displayed and recorded. Just before the first opacity measurement (i.e. OPT0), the opacitometer was calibrated using specific calibrators. Values obtained for each calibrator were as follows:
calibrator No. 1: set to 75,
calibrator No. 2: from 145 to 155,
calibrator No. 3: from 218 to 232.
Just before the second opacity measurement (i.e. OPT2), the opacitometer was calibrated using the calibrator No. 1 set to 75.
Just after each opacity measurement (OPT0 and OPT2), the calibration of the opacitometer was checked by using the calibrator No. 1. The obtained value was between 73 and 77.
Corneal opacity was determined by reading each holder in the right hand chamber of the calibrated opacitometer, versus an empty holder (without cMEM, cornea and glasses), placed in the left hand chamber.
For opacity measurement, care was taken to make sure that no air bubbles were present within the holders containing corneas (by ensuring that each compartment was filled to overflowing with heated cMEM) and each holder was wiped dry.

- Corneal permeability:
After the second opacity measurement, the medium of the anterior chamber was removed and the anterior chamber received 1 mL of a fluorescein solution.
As the test item was a non-surfactant solid, the concentration of the fluorescein solution was 5 mg/mL.
Before use, the fluorescein solution was validated. For this purpose, the solution of fluorescein was diluted in cMEM in order to obtain a 5 µg/mL solution and the Optical Density at a wavelength of 490 nm (OD490 nm) of this dilution was measured. As the value obtained was between 0.850 and 0.940 (see Table 2), the fluorescein solution was validated.
For each series of three corneas, a chronometer started from the fluorescein solution application time of the first cornea of the series. The holders were incubated vertically (cornea positioned horizontally with the fluorescein-treated side uppermost) in a water bath at +32°C (± 1°C) for 90 minutes (± 5 minutes).
At the end of incubation, the maximum volume of cMEM recoverable from the posterior chamber of each holder was transferred into an identified tube. The medium was homogenized prior to determination of OD490 nm, using single-use cuvettes (1 cm path length) and a spectrophotometer (cMEM used as the blank).

OTHER:  Macroscopic examination
After permeability determination, the corneas were removed from the holders and observed for opaque spots, other irregularities and any separation of the epithelium.
Then, the corneas were discarded.

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/3 corneas exposed 4 hours
Value:
23
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other:
Remarks:
One of the three test item-treated corneas (i.e. holder No. 82) presented significantly higher opacity and permeability values and therefore higher individual IVIS score compared to the other two (i.e. individual IVIS = 8, 4 and 56 for holders 64, 60 and 82 respectively). These increased values were consistent with the higher quantity of test item observed on this third cornea.
Other effects / acceptance of results:
OTHER EFFECTS:
- Visible damage on test system:
The individual observation of each cornea treated with the test item, negative and positive controls are reported.
No notable opaque spots or irregularities were observed on the negative control-treated corneas.
Residual test item and fluorescein fixation were observed on the three corneas treated with the test item, with a significantly higher amount of test item observed on the third one (i.e. holder n° 82).
Opacity, fluorescein fixation and thickening of the corneas were observed on those treated with the positive control.


DEMONSTRATION OF TECHNICAL PROFICIENCY: yes

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: yes
- Acceptance criteria met for positive control: yes

See attached document for tables of results.

Interpretation of results:
other: No prediction can be made
Conclusions:
With an IVIS of 23, no prediction can be made as the result is outside the decision criteria (i.e. ≤3 or >55).
Executive summary:

An in vitro eye irritation study was performed according to the OECD Guideline 437 and in compliance with GLP to assess the corneal damage potential of test substance by means of the BCOP assay using fresh bovine cornea.

Corneas obtained from freshly slaughtered calves were mounted in corneal holders. Both chambers of the corneal holder were filled with complemented MEM culture media (cMEM) and pre-incubated for 1 hour and 5 minutes (± 5 minutes) at +32°C.

A single experiment was performed using three corneas for each treated series (test item, positive control and negative control). Before the treatment, a first opacity measurement was performed on each cornea using an opacitometer. The test item was applied undiluted, in a single experiment using a treatment time of 4 hours and the open‑chamber method. Negative and positive controls were applied using the same treatment time and the closed-chamber treatment method. At the completion of the treatment period, all items were removed from the front opening of the anterior chamber and the epithelia were rinsed. A second opacity measurement was then performed. After the second opacity measurement, the medium of the anterior chamber was removed and filled with a fluorescein solution. The holders were then incubated vertically for 90 minutes(± 5 minutes) at +32°C. At the end of the incubation period, the Optical Density of the solution from the posterior chamber of each holder was measured in order to determine the permeability of the cornea. Each cornea was then observed for opaque spots and other irregularities. Residual test item and fluorescein fixation were observed on all corneas treated with the test item, with a larger amount of test item stuck over the corneas No. 82.

All acceptance criteria were fulfilled. The study was therefore considered as valid.

The mean In Vitro Irritancy Score (IVIS) of the test item-treated corneas was: 23.

One of the three test item treated corneas presented a higher individual IVIS value than the two other ones (i.e. individual IVIS = 56 for the corneas No. 82, and IVIS = 8 and 4 for the corneas Nos. 64 and 60, respectively). However, this higher IVIS value for the corneas No. 82 can be explained by the significantly larger amount oftest item noted over this corneas.

Thus and as the mean IVIS was > 3 and ≤ 55, the eye hazard potential of the test item could not be predicted.

Under the test conditions, the test item could not be identified as inducing serious eye damage (UN GHS Category 1) or as a test chemical not requiring classification for eye irritation or serious eye damage (UN GHS No Category).

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

A key study was identified (Newell, 1976). This dermal irritation study was performed according to the Draize Test.

0.5 g of test substance was dermally applied on the intact or abraded side surface of 6 New Zealand White rabbits. Test sites were covered with an occlusive dressing for 24 h. Skin irritation was assessed and scored according to the Draize scale at 24 and 72 h after the removal of the patch.

Test substance caused a minimum amount of edema in one of the six treated rabbits at the 24-hour reading only. The total primary irritation score was 0.04. Reversibility was not assessed.

Eye irritation:

A Weight of Evidence approach was followed for the eye irritation endpoint.

In an old eye irritation study performed according to the Draize Test (Newell, 1976), 0.1 g of test substance was instilled into the left eye of 9 New Zealand White rabbits while the right eye remained untreated and served as control. Test substance was washed from the eye of six rabbits (30 seconds after instillation in three rabbits; 5 minutes after instillation in another three rabbits); and no washing was done in three rabbits. 

In the worst-case "no-wash" group, irritation was observed in conjunctival and iris tissues only. All three rabbits showed circumcorneal injection around the iris at the 1-hour reading. This condition persisted for 3 days. Occasional circumcorneal injection responses were noted in individual rabbits but all effects involving the iris had disappeared by day 4 after treatment. Conjunctival responses were observed and generally involved mild redness, chemosis, and discharge. The treated eye of all rabbits was not judged normal in response until day 7.

Mean scores at 24/48/72h were 0/0/0 out of 80 for Cornea, 1.7/1.7/1.7 out of 10 for Iris and 1.3/0.7/0.7 out of 20 for conjunctivae.

Overall, the degree of eye irritation caused by test substance was mild but transitory.

Additionnaly, an ex vivo eye irritation study (Richez, 2017) was performed according to the OECD guideline 437 (BCOP) and in compliance with GLP to confirm the old in vivo data.

Corneas were exposed to test substance (neat) for 4 hours using the open-chamber method. Negative and positive controls were applied using the same treatment time and the closed-chamber treatment method. At the completion of the treatment period, all items were removed from the front opening of the anterior chamber and the epithelia were rinsed. Opacity measurements were perfomed once before the treatment, and twice after the treatment. After a post-exposure incubation period, optical density was measured in order to determine the permeability of the cornea.

Residual test item and fluorescein fixation were observed on all corneas treated with the test item, with a larger amount of test item stuck over the corneas No. 82.

The mean In Vitro Irritancy Score (IVIS) of the test item-treated corneas was: 23. One of the three test item treated corneas presented a higher individual IVIS value than the two other ones (i.e. individual IVIS = 56 for the corneas No. 82, and IVIS = 8 and 4 for the corneas Nos. 64 and 60, respectively). However, this higher IVIS value for the corneas No. 82 can be explained by the significantly larger amount oftest item noted over this corneas.

CONCLUSION: Although no prediction can be made for the BCOP study, the substance is considered to be non-irritant to the eye considering both the low IVIS (8 and 4) of the corneas No. 64 and 60 and the very low scores obtained in the in vivo study.

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008.

Self classification:

Based on the available data, no additional self-classification is proposed for the registered substance regarding skin and eye irritation according to the Annex I of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.

No data was available regarding respiratory irritation. Not required for substances at the REACH Annex VII tonnage level.