Reaction product of salicylaldehyde and formaldehyde and phenol

Endpoint summary

Description of key information

Skin Irritation in vivo. Zelenák (2012)

Under the conditions of this study, the test material does not require classification as a skin irritant.

Eye Irritation in vivo. Zelenák (2012)

Under the conditions of this study, the test material caused significant conjunctival and corneal irritant effects at one hour after application and the effects were not fully reversible within 3 weeks. The test material requires classification as an eye irritant (Irreversible effects on the eye/serious damage to eyes (Category 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:

25 September 2012 to 09 October 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

2002

Deviations:

yes

Remarks:

(see "Principles of method if other than guideline" for information)

Principles of method if other than guideline:

The guideline states that the relative humidity should be at least 30% and preferably not exceed 70%, other than during room cleaning, the aim should be 50-60% whereas during the study, the relative humidity was humidity range was recorded as 41 - 82%. This deviation is presumed to have no impact on the outcome of the study.

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: ~12 weeks old
- Weight at study initiation: 2960 - 3172 g
- Housing: Rabbits were individually housed in AAALAC approved metal wire rabbit cages (65 x 65 cm with height of 45 cm). Cages were of an open wire structure and cages were placed together to allow some social interaction with rabbit(s) in adjoining cages.
- Diet: ad libitum
- Water: The animals received municipal tap water, as for human consumption, ad libitum, from an automatic system. The drinking water is routinely analysed and is considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.
- Acclimation period: 12 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 3 °C
- Humidity: 41 - 82 %
- Air changes: 15 - 20 air exchanges/hour
- Photoperiod: 12 hours daily, from 6.00 a.m. to 6.00 p.m.

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 g

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3 males

Details on study design:

TEST SITE
- Patch testing was used to detect primary irritating effects of the test material. Three male animals in acceptable health condition were selected for this test.
- Approximately 24 hours prior to the test, the hair was clipped from the back and flanks of the animals. Removal of hair was performed in two steps. The majority of hair was clipped with an electronic hair clipper and the remaining hair was moistened with water and shaved with a razor. The test material was applied to an approximately 6 cm² area of intact skin as follows:
* A single layer of a fine medical gauze (open-weave with large holes) of approximately 5 x 5 cm was placed over the application area,
* The appropriate amount of test material was carefully spread over the application area (the gauze helped maintain the test material in place),
* Three more layers of gauze were placed over the test material,
* These gauze patches were kept in contact with the skin by a patch of clear plastic with a surrounding adhesive hypoallergenic plaster to ensure continued good contact between the moistened test material and the shaved skin.
* The entire trunks of the animals were wrapped with plastic wrap for 4 hours.
* Medical elastic tubing was placed over the plastic to keep it in place.
- An initial test was performed using one animal. One hour after application of the test material, the application site was examined. No severe irritation or corrosive effect was found in the initial test, therefore the bandage was replaced and the exposure continued for a further 3 hours (a total 4 hours exposure). Two additional animals were then included in the study.

REMOVAL OF TEST SUBSTANCE
- After the treatment period, the test material was removed with water at body temperature and with Unguentum hydrophilicum nonionicum

OBSERVATION TIME POINTS
- Clinical Observations: Animals were examined for signs of erythema and oedema, and the responses scored at 60 minutes and then at 24, 48, 72 hours, 1 and 2 weeks after patch removal.
- Measurement of Body Weight: Body weights were recorded at the beginning and at the end of experiment.

SCORING SYSTEM:
- The dermal irritation scores were evaluated according to the scoring system by Draize (1959). The animals were observed for 72 hours and the duration of the study was sufficient to evaluate fully the reversibility or irreversibility of the effects observed.

CLASSIFICATION OF THE TEST MATERIAL
Results were presented and interpreted according to Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging of substances and mixtures:

CATEGORY 1 CORROSIVE:
- A corrosive is a test material that produces destruction of skin tissue, namely, visible necrosis through the epidermis and into the dermis, in at least 1 of 3 tested animals after an exposure of 4 hours. Corrosive reactions are typified by ulcers, bleeding, bloody scabs and, by the end of the observation at 14 days, by discolouration due to blanching of the skin, complete areas of alopecia and scars.
- Corrosive subcategories:
1A: Corrosive in > 1 of 3 animals with < 3 minutes exposure
1B: Corrosive in > 1 of 3 animals with > 3 minutes - ≤ 1 hour exposure
1C: Corrosive in > 1 of 3 animals with > 1 hour - ≤ 4 hours exposure

CATEGORY 2 IRRITANT
- Mean value of for erythema/eschar formation or oedema is greater or equal than 2.3, but less or equal than 4.0 in at least 2 of 3 tested animals from grades at 24, 48 and 72 hours after patch removal or, if reactions are delayed from grades on 3 consecutive days after the onset of skin reactions; or
- Inflammation that persists to the end of the observation period normally 14 days in at least 2 animals, particularly taking into account alopecia (limited area), hyperkeratosis, hyperplasia, and scaling; or
- In some cases where there is a pronounced variability of response among animals, with very definite positive effects related to chemical exposure in a single animal but less than the criteria above.

CATEGORY 3 MILD IRRITANT
- Mean value for erythema/eschar formation or oedema is greater than 1.5, but less than 2.3 in at least 2 of 3 tested animals from grades at 24, 48 and 72 hours after patch removal, or if reactions are delayed, from grades on 3 consecutive days after the onset of skin reactions (when not included in the irritant category above).

PRIMARY IRRITATION INDEX
- Primary Irritation Index was calculated by added together the scores for erythema and oedema obtained at 24, 48 and 72 hours after completion of the 4 hours exposure for all animals (18 values) and divided by 9 (number of test sites x 3 scoring intervals).
- This index was used to classify the test material according to the following scheme devised by Draize (1959):
Primary Irritation Index Classification:
0 - non-irritant
> 0 – 2 - mild irritant
> 2 – 5 - moderate irritant
> 5 – 8 - severe irritant

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritant / corrosive response data:

- At observation one, 24, 48, 72 hours, 1 and 2 weeks after patch removal, there was no observed clinical signs noted on the skin of the treated animals. However, orange-reddish staining was observed on the treated skin in all animals after dosing from Day 1 to Day 7 which were reversible by the end of the observation period.
- As no clinical signs were observed the study was terminated after the 2 weeks observation.
- The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for erythema and oedema were 0.00, 0.00 and 0.00 respectively.
- The Primary Irritation Index (considering readings at 24, 48 and 72 hours after patch removal) was calculated as 0.00.

Other effects:

MORTALITY
- There was no mortality observed during the study.

BODY WEIGHTS
- There was no effect of treatment on body weight.

CLINICAL OBSERVATION
- General Daily Examination: There were no treatment-related clinical signs noted.

Interpretation of results:

other: Not classified in accordance with EU criteria

Conclusions:

Under the conditions of this study, the test material does not require classification as a skin irritant.

Executive summary:

The skin irritation potential of the test material was investigated in accordance with the standardised guideline OECD 404, under GLP conditions.

An acute skin irritation study was performed with the test material in New Zealand White rabbits. Parameters monitored during this study included mortality, body weight measurements and clinical observations. The irritancy of the test material was evaluated according to the Draize method.

During the study, 0.5 g test material was applied to the skin of the experimental animals. The test material was applied as a single dose. Sufficient water to dampen the material was used to ensure good contact with the skin and an adhesive clear plastic patch was applied. The trunk was wrapped in clear plastic with medical tubing used to hold the patch in place. The untreated skin of each animal served as control. After 4 hours, the remaining test material was removed with water at body temperature and with Unguentum hydrophilicum nonionicum.

To assess skin irritation, animals were examined at 1, 24, 48, 72 hours, 1 and 2 weeks after the patch removal. Additional general examinations were performed daily.

There was no mortality or systemic clinical changes related to test material administration. There was no effect of treatment on body weight.

At observation one, 24, 48, 72 hours, 1 and 2 weeks after patch removal, there were no observed clinical signs noted on the skin of the treated animals. However, orange-reddish staining was observed on the treated skin in all animals after dosing from Day 1 to Day 7 which were reversible by the end of the observation period. As no clinical signs were observed the study was terminated after the 2 weeks observation.

The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for erythema and oedema were 0.00, 0.00 and 0.00 respectively. The Primary Irritation Index (considering readings at 24, 48 and 72 hours after patch removal) was calculated as 0.00.

Under the conditions of this study, the test material does not require classification as a skin irritant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02 October 2012 to 24 October 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

2002

Deviations:

yes

Remarks:

(see "Principles of method if other than guideline" for information)

Principles of method if other than guideline:

The Guideline states that the relative humidity should be at least 30% and preferably not exceed 70%, other than during room cleaning, the aim should be 50-60%. The range in the study was reported to be 38 - 82%. This deviation is considered to have no impact on the outcome of the study and interpretation of the results.

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: ~13 weeks old
- Weight at study initiation: 3157 g
- Housing: Rabbits were individually housed in AAALAC approved metal wire rabbit cages. Cages were of an open wire structure and cages were placed together to allow some social interaction with rabbit(s) in adjoining cages.
- Diet: ad libitum
- Water: The animals received municipal tap water, as for human consumption, ad libitum, from an automatic system. The quality control analysis is performed once every three months and microbiological assessment is performed monthly
- Acclimation period: 19 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 3 °C
- Humidity: 38 - 82%
- Air changes: 15 - 20 air exchanges/hour
- Photoperiod: 12 hours daily, from 6.00 a.m. to 6.00 p.m.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 g

Duration of treatment / exposure:

The eyelids were held closed for a few seconds to prevent the loss of the test material.

Observation period (in vivo):

3 weeks

Number of animals or in vitro replicates:

1 male

Details on study design:

TREATMENT
- Three male animals in acceptable health condition were selected for the test. Care was taken to select only those animals that had a normal eye condition and any with ocular lesions were rejected.
- An initial test was performed using one animal. The test material was instilled into the conjunctival sac of the left eye. The eyelids were held closed for a few seconds to prevent the loss of the test material. The contra lateral eye served as the control. Immediately after the administration of the test material, an assessment of the initial pain reaction was made according to a six point scale.
- After consideration of the ocular responses produced in the first animal, one hour after the treatment of the first animal, two additional animals were treated.

REMOVAL OF TEST SUBSTANCE
- The treated eye was rinsed with physiological saline solution at 1 hour observation.

OBSERVATIONS
- The eyes were examined at 1, 24, 48, 72 hours, 1, 2 and 3 weeks after treatment. The duration of the observation period was sufficient to identify reversibility or irreversibility of changes. Any clinical signs of toxicity or signs of ill-health during the study were recorded. At the end of the observation period, the animal was sacrificed by intramuscular injections of CP-Ketamin 10 % and CP-Xylazin 2 % followed by iv. Euthasol® 40 % anaesthesia. Death was verified by checking pupil and corneal reflex and the absence of respiration.
- Measurement of Body Weight: Individual body weight was recorded on the day of treatment and end of the experiment.

SCORING SYSTEM:
- The eye irritation scores were evaluated according to the scoring system by Draize (1977) and OECD 405 (24 April 2002).

CLASSIFICATION
Individual reactions of the animals were recorded at each observation time. The nature, severity and duration of all lesions observed were described.
Results were presented and interpreted according to Regulation (EC) No 1272/2008, as follows:

Irreversible effects on the eye/serious damage to eyes (Category 1)
- Substances that have the potential to seriously damage the eyes are classified in Category 1 (irreversible effects on the eye). These observations include animals with grade 4 cornea lesions and other severe reactions (e.g., destruction of cornea) observed at any time during the test, as well as persistent corneal opacity, discolouration of the cornea by a dye substance, adhesion, pannus, and interference with the function of the iris or other effects that impair sight.
- Category for irreversible eye effects
If, when applied to the eye of an animal, a substance produces:
- at least in one animal effects on the cornea, iris or conjunctiva that are not expected to reverse or have not fully reversed within an observation period of normally 21 days; and/or
- at least in 2 of 3 tested animals, a positive response of corneal opacity ≥ 3 and/or iritis > 1.5 calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material.

Reversible effects on the eye/irritating to eyes (Category 2)
- Substances that have the potential to induce reversible eye irritation are classified in Category 2 (irritating to eyes).
- Category for reversible eye effects
If, when applied to the eye of an animal, a substance produces:
- at least in 2 of 3 tested animals, a positive response of: corneal opacity ≥ 1 and/or iritis ≥ 1, and/or conjunctival redness ≥ 2 and/or conjunctival oedema (chemosis) ≥ 2 calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material, and which fully reverses within an observation period of 21 days.

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

fully reversible within: 3 weeks

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not fully reversible within: 3 weeks

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not fully reversible within: 3 weeks

Irritation parameter:

conjunctivae score

Remarks:

discharge

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 3 weeks

Irritant / corrosive response data:

EXAMINATION OF EYE IRRITANCY
- The eyes were examined at 1, 24, 48, 72 hours, 1, 2, and 3 weeks after the application.
- Initial Pain Reaction (IPR) (score 1) was observed in the animal.
- One hour after the application: Conjunctival redness (score 2), chemosis (score 2), discharge (score 3) were found in the animal. Corneal opacity (score 1, area 4) was observed in the animal. Test material staining was observed around the eye area.
- At 24, 48 and 72 hours after the application: Conjunctival redness (score 2), chemosis (score 4), discharge (score 3) were found in the animal. Corneal opacity (score 2, area 3) was observed in the animal.
- At 1 week after the application: Conjunctival redness (score 2), chemosis (score 2), discharge (score 3) were found in the animal. Corneal opacity (score 2, area 4) was observed in the animal.
- At 2 weeks after the application: Conjunctival redness (score 1), chemosis (score 1), discharge (score 2) were found in the animal. Corneal opacity (score 2, area 4) was observed in the animal.
- At 3 weeks after the application: Conjunctival redness (score 1), was noted in the animal. Corneal opacity (score 2, area 4) was observed in the animal.
- The animal individual mean scores (considering readings at 24, 48 and 72 hours after the treatment) were as follows:
chemosis: 4.00
discharge: 3.00
redness: 2.00
cornea opacity: 2.00
iris: 0.00

Other effects:

MORTALITY
- There was no mortality observed during the study.

BODY WEIGHTS
- The body weight and body weight change were considered to be normal with no indication of a treatment related effect.

CLINICAL OBSERVATION
- General daily examination: There were no clinical signs observed that could be related to treatment.

Table 1: Individual Scores for Ocular Irritation

Time	Score of Irritation
	Conjunctivae			Opacity of Cornea		Iris	Control Eye
	R	CH	D	OD	OE	R
1 hour	2	2	3	1	4	0	0
24 hours	2	4	3	2	3	0	0
48 hours	2	4	3	2	3	0	0
72 hours	2	4	3	2	3	0	0
1 week	2	2	3	2	4	0	0
2 weeks	1	1	2	2	4	0	0
3 weeks	1	0	0	2	4	0	0

R = Redness, OD = Opacity degree of density, CH = Chemosis, OE = Extent of opaque area, D = Discharge

Interpretation of results:

other: EU criteria: Category 1, H318: Causes serious eye irritation

Conclusions:

Under the conditions of this study, the test material caused significant conjunctival and corneal irritant effects at one hour after application and the effects were not fully reversible within 3 weeks. The test material requires classification as an eye irritant (Irreversible effects on the eye/serious damage to eyes (Category 1)).

Executive summary:

The eye irritation potential of the test material was investigated in accordance with the standardised guideline OECD 405, under GLP conditions.

An acute eye irritation study of the test material was performed in New Zealand White rabbits. The test material was placed into the conjunctival sac of the left eye of the single animal. The untreated right eye served as control. An amount of 0.1 g of the test material was administered as a single dose. For ethical reasons, an initial test was performed using a single animal. As this test indicated that the test material is severely irritating or corrosive to the eye, further testing was not be performed.

Individual body weight was recorded on the day of treatment and end of the experiment. Morbidity and clinical signs of toxicity were checked daily. The eyes were examined at 1, 24, 48, 72 hours, 1, 2 and 3 weeks after the application.

Initial Pain Reaction (IPR) (score 1) was observed in the animal. One hour after the application: Conjunctival redness (score 2), chemosis (score 2), discharge (score 3) were found in the animal. Corneal opacity (score 1, area 4) was observed in the animal. Test material staining was observed around the eye area. At 24, 48 and 72 hours after the application: Conjunctival redness (score 2), chemosis (score 4), discharge (score 3) were found in the animal. Corneal opacity (score 2, area 3) was observed in the animal.

At 1 week after the application: Conjunctival redness (score 2), chemosis (score 2), discharge (score 3) were found in the animal. Corneal opacity (score 2, area 4) was observed in the animal. At 2 weeks after the application: Conjunctival redness (score 1), chemosis (score 1), discharge (score 2) were found in the animal. Corneal opacity (score 2, area 4) was observed in the animal. At 3 weeks after the application: Conjunctival redness (score 1), was noted in the animal. Corneal opacity (score 2, area 4) was observed in the animal.

No clinical signs of systemic toxicity were observed in the animal during the study and no mortality occurred. The body weights of the animal were considered to be within the normal range of variability.

The animal individual mean scores (considering readings at 24, 48 and 72 hours after the treatment) were as follows: chemosis: 4.00, discharge: 3.00, redness: 2.00, cornea opacity: 2.00 and iris: 0.00.

Under the conditions of this study, the test material caused significant conjunctival and corneal irritant effects at one hour after application and the effects were not fully reversible within 3 weeks. The test material requires classification as an eye irritant (Irreversible effects on the eye/serious damage to eyes (Category 1)).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation in vivo. Zelenák (2012)

The skin irritation potential of the test material was investigated in accordance with the standardised guideline OECD 404, under GLP conditions. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

An acute skin irritation study was performed with the test material in New Zealand White rabbits. Parameters monitored during this study included mortality, body weight measurements and clinical observations. The irritancy of the test material was evaluated according to the Draize method.

During the study, 0.5 g test material was applied to the skin of the experimental animals. The test material was applied as a single dose. Sufficient water to dampen the material was used to ensure good contact with the skin and an adhesive clear plastic patch was applied. The trunk was wrapped in clear plastic with medical tubing used to hold the patch in place. The untreated skin of each animal served as control. After 4 hours, the remaining test material was removed with water at body temperature and with Unguentum hydrophilicum nonionicum.

To assess skin irritation, animals were examined at 1, 24, 48, 72 hours, 1 and 2 weeks after the patch removal. Additional general examinations were performed daily.

There was no mortality or systemic clinical changes related to test material administration. There was no effect of treatment on body weight.

At observation one, 24, 48, 72 hours, 1 and 2 weeks after patch removal, there were no observed clinical signs noted on the skin of the treated animals. However, orange-reddish staining was observed on the treated skin in all animals after dosing from Day 1 to Day 7 which were reversible by the end of the observation period. As no clinical signs were observed the study was terminated after the 2 weeks observation.

The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for erythema and oedema were 0.00, 0.00 and 0.00 respectively. The Primary Irritation Index (considering readings at 24, 48 and 72 hours after patch removal) was calculated as 0.00.

Under the conditions of this study, the test material does not require classification as a skin irritant.

Eye Irritation in vivo. Zelenák (2012)

The eye irritation potential of the test material was investigated in accordance with the standardised guideline OECD 405, under GLP conditions. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

An acute eye irritation study of the test material was performed in New Zealand White rabbits. The test material was placed into the conjunctival sac of the left eye of the single animal. The untreated right eye served as control. An amount of 0.1 g of the test material was administered as a single dose. For ethical reasons, an initial test was performed using a single animal. As this test indicated that the test material is severely irritating or corrosive to the eye, further testing was not be performed.

Individual body weight was recorded on the day of treatment and end of the experiment. Morbidity and clinical signs of toxicity were checked daily. The eyes were examined at 1, 24, 48, 72 hours, 1, 2 and 3 weeks after the application.

Initial Pain Reaction (IPR) (score 1) was observed in the animal. One hour after the application: Conjunctival redness (score 2), chemosis (score 2), discharge (score 3) were found in the animal. Corneal opacity (score 1, area 4) was observed in the animal. Test material staining was observed around the eye area. At 24, 48 and 72 hours after the application: Conjunctival redness (score 2), chemosis (score 4), discharge (score 3) were found in the animal. Corneal opacity (score 2, area 3) was observed in the animal.

At 1 week after the application: Conjunctival redness (score 2), chemosis (score 2), discharge (score 3) were found in the animal. Corneal opacity (score 2, area 4) was observed in the animal. At 2 weeks after the application: Conjunctival redness (score 1), chemosis (score 1), discharge (score 2) were found in the animal. Corneal opacity (score 2, area 4) was observed in the animal. At 3 weeks after the application: Conjunctival redness (score 1), was noted in the animal. Corneal opacity (score 2, area 4) was observed in the animal.

No clinical signs of systemic toxicity were observed in the animal during the study and no mortality occurred. The body weights of the animal were considered to be within the normal range of variability.

The animal individual mean scores (considering readings at 24, 48 and 72 hours after the treatment) were as follows: chemosis: 4.00, discharge: 3.00, redness: 2.00, cornea opacity: 2.00 and iris: 0.00.

Under the conditions of this study, the test material caused significant conjunctival and corneal irritant effects at one hour after application and the effects were not fully reversible within 3 weeks. The test material requires classification as an eye irritant (Irreversible effects on the eye/serious damage to eyes (Category 1)).

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the substance does not require classification with respect to skin irritation. The substance requires classification as an eye irritant (Irreversible effects on the eye/serious damage to eyes (Category 1, H318: Causes serious eye irritation).