Registration Dossier

Administrative data

Description of key information

Not irritating in an in vivo skin irritation study in rabbits.
Two in vivo studies in rabbits are available for eye irritation: one showing irreversible damage in one animal and one showing reversible irritating effects.

One BCOP study is available showing no corrosive or highly irritant properties of the test substance.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation / corrosion, other
Remarks:
skin irritation in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1998-05-18 to 1998-05-25
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP study following OECD guideline with several deviations: no details about test substance, no certificate of analysis, no individual body weights.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
no details about test substance, no certificate of analysis
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Jegard (Yffiniac, France)
- Weight at study initiation: average weight 2.4 kg
- Housing: individual housing on floor grid
- Diet (e.g. ad libitum): pelleted diet from ERGILAP Anco, COFNA (Tours, France), ad libitum
- Acclimation period: at least 5 days

IN-LIFE DATES: From: 1998-05-18 To: 1998-05-25
Type of coverage:
semiocclusive
Preparation of test site:
other: hair clipping
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL/rabbit



Duration of treatment / exposure:
4 h
Observation period:
14 days
Number of animals:
3 females
Details on study design:
TEST SITE
- Area of exposure: 2.5 X 2.5 cm
- Type of wrap if used: 10 cm wide stretch tape (varicose vein tape)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test preparation removed with cotton wool moistened with distilled water
- Time after start of exposure: 4 h

SCORING SYSTEM: Erythema and eschar formation
-no erythema............................................................................................................................0
-very slight erythema ( barely perceptible ).........................................................................1
-Well defined erythema............................................................................................................2
-Moderate to severe erythema...............................................................................................3
-Severe erythema (beet redness) to slight eschar formation ( injuries in depth ).........4

Oedema formation
-No oedema................................................................................................................................0
-Very slight oedema ( barely perceptible ).............................................................................1
-Slight oedema ( edges of area well defined by definite raising ).......................................2
-Moderate oedema ( raised approximately 1 mm )...............................................................3
-Severe oedema ( raised more than 1 mm and extending beyond area of exposure )...4
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: day 7
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: day 6
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
mean individual scores
Time point:
other: 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: day 6
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: day 5
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
mean individual score
Time point:
other: 24, 48 and 72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: day 6
Irritant / corrosive response data:
Under experimental conditions, the application of test substance for 4 h to the skin of the rabbit produced, 1 hour after patch removal, slight to well defined erythema and oedema observed in all the animals. The reactions were decreased in less than 5 days (D6) for 2 animals and 6 days (D7) for the third rabbit.
Other effects:
There is a cutaneous dryness then rugosity from D3 to D14.

Individual values of skin reactions

Animal N°

SCORES

Mean scores

SCORES

D1 (1h)

24 h

48 h

72 h

Over 24-48-72 h

D5

D6

D7

Erythema

7307

2

2

1

1

1.3

1

1

0

7308

2

1

1

1

1.0

1

0

/

7309

1

1

0

0

0.3

0

0

/

Oedema

7307

1

1

1

1

1.0

1

0

0

7308

2

2

1

1

1.3

0

0

/

7309

2

2

1

1

1.3

1

0

/

/ : no reading

Interpretation of results:
GHS criteria not met
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According to the criteria of directive 67/548/EEC, the test item should not be classified as skin irritant.
Executive summary:

The dermal irritation study was conducted according to OECD guideline 404 in compliance with GLP. Three healthy adult New Zealand white rabbits were exposed to 0.5 mL/rabbit of the test item on clipped skin from the dorsal area for 4 hours in semi-occlusive conditions. Skin reactions were observed at 1, 24, 48 and 72 h after removal of the substance until the disappearance of the effects (day 7).1 hour after patch removal there was slight to well defined erythema and oedema in all animals. Mean individual scores were 1.3, 1.0 and 0.3 for erythma and 1.0, 1.3 and 1.3 for oedema. The reactions were reversible within 5 days (D6) for two animals and 6 days (D7) for the third rabbit.

Therefore, the test item should not be classified as irritating to the skin according to the criteria of directive n°67/548/EEC and CLP regulation (EC) n°1272/2008.

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:
1985
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Study performed similarly to OECD guideline 405 with deviations: lack of data about test substance, no details about housing conditions and scoring system different from guideline; study conducted in only one animal.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
lack of data about test substance, no details about housing conditions and scoring system different from guideline; study conducted in only one animal.
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: Nine weeks
- Weight at study initiation: 1.9 kg
- Housing: Housed individually in cages with wire mesh floor
- Diet: Certified pelleted commercial rabbit diet; ad libitum
- Water: Tap water; ad libitum
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume with unit): 100 µL
Duration of treatment / exposure:
No washing was done
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
One male
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: No
- Time after start of exposure: Not applicable

SCORING SYSTEM:
CORNEA
Normal…0
Any change from normal, including slight dulling of corneal luster; scattered or diffuse areas of opacity, or loss of corneal epithelium. Iris clearly visible…1
Easily discernible, greyish, translucent areas, details of iris slightly obscured…2
Grey-white areas, no details of iris visible, size of pupil barely discernible…3
Complete corneal opacity, iris not discernible…4

IRIS
Normal…0
Any divergence from normal, congestion of iridial vessels, deepening on folds…1
Severe congestion of iridial vessels or deepening on folds; loss of iridial reflex to light…2

Area of cornea or iris affected
Less than ¼ of area affected…1
Between ¼ and ½ of area affected…2
Between ½ and ¾ of area affected…3
Between ¾ and whole area affected…4

CONJUNCTIVAE
Redness (palpebral and bulbar conjunctivae and nictitating membrane)
Vessel normal…0
Some vessel definitely injected…1
Diffusion, crimson red, individual vessel not easily discernible…2
Diffuse beefy red…3

Chemosis
No swelling…0
Any swelling above normal…1
Obvious swelling with partial eversion of eyelids…2
Swelling with lids about half closed…3
Swelling with lids more than half closed…4

Discharge
No discharge…0
Any discharge different from normal….1
Discharge with moistening of lids and hairs just adjacent to the lids…2
Discharge with moistening of lids and considerable area round eye….3

TOOL USED TO ASSESS SCORE: Macroscopical observations were performed using hand-held torch and corneal thickness was assessed using slit lamp.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 6 days
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 2 days
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
1.33
Max. score:
3
Reversibility:
fully reversible within: 6 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 4 days
Irritant / corrosive response data:
- Loss of small area of corneal epithelium with slight corneal swelling and iritis; moderate conjunctivitis with copious discharge
- Irritation completely resolved by Day 7
Other effects:
None

Table 1: Daily observation of ocular reactions

 

Observation period

Corneal score

Conjunctive

Iris

Opacity

Area

% Swelling

Redness

Chemosis

Discharge

15 min.

-

-

-

1

0

 

-

Day 2

1

1

30

2

1

3

1

Day 3

1

1

0

1

1

1

0

Day 4

1

1

 

1

1

1

0

Day 5

1

1

 

1

0

0

0

Day 7

0

 

 

0

0

0

0

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Remarks:
Criteria used for interpretation of results: other: Annex VI to the Directive 67/548/EEC
Conclusions:
Based on the results obtained with one animal, the test item is classified as ‘R36 Irritating to eyes’ according to Directive 67/548/EEC and as ‘Irritating to eye (Category 2)’ according to CLP Regulation (EC) n° 1272/2008.
Executive summary:

In an eye irritation study conducted similarly to OECD guideline 405, one healthy male rabbit of the New Zealand White strain was exposed to 100 µL of undiluted test item in one of the eyes. The eyes were assessed for conjunctival responses 15 min after treatment and corneal, conjunctival and iridial responses were observed at 1, 2, 3, 4 and 6 days after treatment.

 

Instillation of the test item resulted in loss of small area of corneal epithelium with slight corneal swelling, slight iritis and moderate conjunctivitis with copious discharge. The irritation completely resolved within 6 days. Mean individual scores at 24, 48 and 72 hours after exposure for the animal were 1 for corneal score, 0.33 for iris score, 1.33 for conjunctivae score and 1 for chemosis score.

 

Based on the results obtained with one animal, the test item is classified as ‘R36 Irritating to eyes’ according to Directive 67/548/EEC and as ‘Irritating to eye (Category 2)’ according to CLP Regulation (EC) n° 1272/2008.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
From September 01 to October 06, 1986
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Study performed similarly to OECD guideline 405 with deviations: lack of data about test substance, no details about housing conditions and scoring system different from guideline.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
lack of data about test substance, no details about housing conditions and scoring system different from guideline.
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: Nine weeks
- Weight at study initiation: 2 kg
- Housing: Housed individually in cages with wire mesh floor
- Diet: Certified pelleted commercial rabbit diet; ad libitum
- Water: Tap water; ad libitum
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume with unit): 100 µL

Duration of treatment / exposure:
No washing was done
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
One male
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: No
- Time after start of exposure: Not applicable

SCORING SYSTEM:
CORNEA
Normal…0
Any change from normal, including slight dulling of corneal luster; scattered or diffuse areas of opacity, or loss of corneal epithelium. Iris clearly visible…1
Easily discernible, greyish, translucent areas, details of iris slightly obscured…2
Grey-white areas, no details of iris visible, size of pupil barely discernible…3
Complete corneal opacity, iris not discernible…4

IRIS
Normal…0
Any divergence from normal, congestion of iridial vessels, deepening on folds…1
Severe congestion of iridial vessels or deepening on folds; loss of iridial reflex to light…2

Area of cornea or iris affected
Less than ¼ of area affected…1
Between ¼ and ½ of area affected…2
Between ½ and ¾ of area affected…3
Between ¾ and whole area affected…4

CONJUNCTIVAE
Redness (palpebral and bulbar conjunctivae and nictitating membrane)
Vessel normal…0
Some vessel definitely injected…1
Diffusion, crimson red, individual vessel not easily discernible…2
Diffuse beefy red…3

Chemosis
No swelling…0
Any swelling above normal…1
Obvious swelling with partial eversion of eyelids…2
Swelling with lids about half closed…3
Swelling with lids more than half closed…4

Discharge
No discharge…0
Any discharge different from normal….1
Discharge with moistening of lids and hairs just adjacent to the lids…2
Discharge with moistening of lids and considerable area round eye….3

TOOL USED TO ASSESS SCORE: Macroscopical observations were performed using hand-held torch and corneal thickness was assessed using slit lamp.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 4 days
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
1.66
Max. score:
3
Reversibility:
fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 4 days
Irritant / corrosive response data:
- Loss of epithelium from half of the cornea with slight corneal swelling; moderate conjunctivitis and iritis
- Development of persistent pannus in the eye on Day 4
Other effects:
None

Table 1: Daily observation of ocular reactions

 

Observation period

Corneal score

Conjunctive

Iris

Opacity

Area

% Swelling

Redness

Chemosis

Discharge

15 min.

-

-

-

1

1

-

-

Day 2

1

3

35

2

1

1

1

Day 3

1

2

31

2

1

1

1

Day 4

1

1

39

1

1

1

1

Day 5

1

1

19

1

1

0

0

Day 8

1

1

0

1

0

0

0

Day 10

1

1

 

1

0

0

0

Day 12

1

1

 

1

0

0

0

Day 15

1

1

 

1

0

0

0

Day 19

1

1

 

1

0

0

0

Day 22

1

1

 

0

0

0

0

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on results obtained with one animal, the test item has to be classified as irritating to eyes category 1 or 2 according to Directive 67/548/EEC and CLP Regulation (EC) n° 1272/2008. This classification has to be confirmed by an eye corrosive study.
Executive summary:

In an eye irritation study conducted similarly to OECD guideline 405, one healthy male rabbit of the New Zealand White strain was exposed to 100 µL of undiluted test item in one of the eyes. The eyes were assessed for conjunctival responses 15 min after treatment and corneal, conjunctival and iridial responses were observed at 1, 2, 3, 4, 7, 9, 11, 14, 16, 18 and 21 days after treatment.

 

Instillation of the test item resulted in loss of epithelium from half of the cornea with slight corneal swelling, moderate conjunctivitis and iritis and development of persistent pannus in the eye on Day 4. Mean individual scores at 24, 48 and 72 hours after exposure for the animal were 1 for corneal score, 1 for iris score, 1.66 for conjunctivae score and 1 for chemosis score. Corneal opacity was observed not to be fully reversible within 21 days.

 

Therefore, the test item has to be classified as irritating to eyes category 1 or 2 according to Directive 67/548/EEC and CLP Regulation (EC) n° 1272 /2008. This classification hyas to be confirmed by an eye corrosive study.

Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Recent study well conducted, well described and in compliance with GLP
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
other: OECD guideline N° 437: Bovine Corneal Opacity and Permeability test method for identifying ocular corrosives and severe irritants
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Species:
other: calf
Strain:
not specified
Details on test animals or tissues and environmental conditions:
TEST SYSTEM
- Source: Bovine eyes were collected at the slaughter houses of la Talaudière - France
- Age at study initiation: bovine eyes from cattle less than 12 months
- carried in a stable medium (Hanks medium buffered with sodium bicarbonate), at room temperature, and prepared 4 hours maximum after killing the animals
Vehicle:
unchanged (no vehicle)
Controls:
other: Negative control: 3 eyes treated with sodium chloride at 0.9% (W/V); Positive control: 3 eyes treated with ethanol at 100%.
Amount / concentration applied:
750 µL
Duration of treatment / exposure:
10 ± 1 min
Observation period (in vivo):
not applicable
Number of animals or in vitro replicates:
3 eyes for each product (test sample, negative and positive controls)
Details on study design:
After the application of the test item on the cornea, the eye was rinsed at least 3 times with nutritive medium with phenol red at 32 ± 1°C.

Analysed parameters: Corneal opacification was measured using an OP KIT opacitometer. The initial opacity reading (OPT0) was subtracted from the post incubation opacity (OPT2 – opacity after rinsing and 2-h incubation). Permeability was assessed by measuring the passage of fluorescein stain through the cornea: the amount of fluorescein leakage was determined spectrophotometrically (optical density at 490 nm – DO 490).
Irritation parameter:
in vitro irritation score
Run / experiment:
10 min
Value:
5.6
Remarks on result:
other: +/- 3.1 (SD)
Irritant / corrosive response data:
See table 1
Other effects:
no data

The results of the positive control are in conformity with historical data.

The results of the opacity and the OD of the negative control are in conformity with criteria of validity of the test.

The results of the OD of fluorescein are in conformity with the criteria of validity of the test.

Table 1:Results of the BCOP test

Holder N°

Treatment

OPT0

OPT2

OPT2- OPT0

Corrected opacity

DO

Corrected DO

Score OPc+15DOc

91

Negative control

5

6

1

-

0.009

-

-

440

4

4

0

-

0.023

-

-

34

6

5

-1

-

0.023

-

-

Mean

 

 

 

0.0

0.018

-

-

Standard deviation

 

 

 

1.0

0.008

-

-

28

Ethanol (positive Control)

6

21

15

15.0

1.654

1.636

39.5

170

6

22

16

16.0

1.535

1.535

39.0

84

5

26

21

21.0

1.635

1.617

45.3

Mean

 

 

 

17.3

-

1.596

41.3

Standard deviation

 

 

 

3.2

-

0.054

3.5

12

2 -ETHYL-4(2,2,3 -TRIMETHYL-3 -CYCLOPENTEN-1 -YL)-2 -BUTEN-1 -OL

4

11

7

7.0

0.166

0.148

9.2

13

4

5

1

1.0

0.216

0.198

4.0

32

5

7

2

2.0

0.134

0.116

3.7

Mean

 

 

 

3.3

-

0.154

5.6

Standard deviation

 

 

 

3.2

-

0.041

3.1

OPT0: opacity before treatment

OPT2: opacity 2 hours after rinsing

Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The test item is not classified as corrosive or severely irritant for the isolated bovine cornea, after 10 minutes of contact.
Executive summary:

In an in vitro eye corrosivity and severe irritancy test (BCOP test for Bovine Corneal Opacity and Permeability), performed according to the OECD guideline 437 and in compliance with GLP, 3 bovine cornea were treated with undiluted 2-ethyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-buten-1-ol. The test substance was in contact with cornea for 10 minutes and then the eyes were rinsed at least 3 times. Corneal opacity was measured thanks to an opacitometer 2 hours after the treatment. The corneal permeability was quantified by the measurement of the optical density 90 min after the addition of a fluorescein solution to the treated cornea.

Negative control (sodium chloride solution) and positive control (Ethanol) were also used to validate the study and the results were acceptable for these controls.

The in vitro irritancy score (IVIS) for the test item was 5.6 ± 3.1. Therefore, it is not classified as corrosive or severly irritant for the isolated bovine cornea, after 10 minutes of contact.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In an in vivo skin irritation study conducted according to OECD guideline 404 and in compliance with GLP, mean individual scores at 24, 48 and 72 h were 1.3, 1.0 and 0.3 for erythma and 1.0, 1.3 and 1.3 for oedema. The reactions were reversible within 5-6 days after treatment.

For eye irritation, two in vivo studies performed in only one animal each (Klimisch score 4) and one in vitro recent study (Klimisch score 1, not sufficient for classification) were available; therefore a weight of evidence approach was selected.

The two in vivo studies were performed in only one animal each: one showed loss of small area of corneal epithelium with slight corneal swelling, slight iritis and moderate conjunctivitis with copious discharge. The irritation completely resolved within 6 days. Mean individual scores at 24, 48 and 72 hours after exposure for the animal were 1 for corneal score, 0.33 for iris score, 1.33 for conjunctivae score and 1 for chemosis score. The other study showed loss of epithelium from half of the cornea with slight corneal swelling, moderate conjunctivitis and iritis and development of persistent pannus in the eye on Day 4. Mean individual scores at 24, 48 and 72 hours after exposure for the animal were 1 for corneal score, 1 for iris score, 1.66 for conjunctivae score and 1 for chemosis score. Corneal opacity was observed not to be fully reversible within 21 days.

A recent GLP in vitro BCOP study showed IVIS (In Vitro Irritation Score) = 5.6±3.1; as this score is lower than 11, the test item is not considered to have corrosive or highly irritant properties for eye.


Justification for selection of skin irritation / corrosion endpoint:
GLP study following OECD guideline 404 with deviations that do not compromise the reliability of the study therefore it is considered as appropriate and reliable to complete this endpoint.

Justification for selection of eye irritation endpoint:
Several studies were used to complete this endpoint therefore no key study was selected.

Effects on eye irritation: irritating

Justification for classification or non-classification

As the test item shows slight reversible irritating effets on rabbit skin in a GLP study conducted according to OECD guideline 404, it is not classified for skin irritation according to Directive 67/548/EEC and CLP Regulation (EC) n° 1272/2008.

In two old in vivo eye irritation studies in rabbits using one animal each, one animal had irritating effects reversible within 6 days and one animal had irreversible eye damage (pannus formation and corneal opacity not fully reversed), suggesting a corrosive or highly irritating effect of the substance. However, these studies were not totally reliable based on the non-GLP compliance, the lack of details about the test substance and the difference in scoring scale compared to the OECD guideline 405. A recent negative GLP BCOP study shows that the test item does not have corrosive or highly irritant properties for eye.

In conclusion, based on in vivo studies, the substance has irritating properties for eye, with a suspected corrosive/highly irritant effect that was not confirmed in a recent "negative" GLP BCOP study. Thus, the test item is classified ‘R36 Irritating to eyes’ according to Directive 67/548/EEC and as ‘Irritating to eye (Category 2)’ according to CLP Regulation (EC) n° 1272/2008.