Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Skin Irritation In Vivo: Dange (1994)

Under the conditions of this study, the test material did not produce positive criteria in any rabbit and was considered non-irritant to rabbit skin.

Skin Irritation in Vivo Supporting Study: Smith (1990)

Under the conditions of this study, the test material was determined to be not irritating in accordance with EU criteria.

Skin Irritation/Corrosion In Vitro: Waiver

An in vitro skin irritation/corrosion study does not need to be conducted because adequate data from in vivo skin irritation studies are available.

Eye irritation In Vivo: Smith (1990)

Under the conditions of this study the test material was considered to be 'severely irritant'with irreversible effects to the eye.

Eye Irritation In Vitro: Waiver

An in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
17 March 1994 to 15 April 1994
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:
1981
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Housing: Rabbits were housed individually in plastic cages.
- Diet: Pelleted diet available ad libitum.
- Water: Tap water from the municipal water supply, filtered and softened was available ad libitum.
- Acclimation period: They were acclimatised to laboratory conditions for 26 days prior to treatment.

ENVIRONMENTAL CONDITIONS
- Temperature: 19 ± 2 °C
- Humidity: 60 ± 15 °C
- Air changes: 15 air changes per hour (average, not monitored)
- Photoperiod: 12-hour light, 12-hour dark cycles

IN-LIFE DATES
- From: 17 March 1994
- To: 15 April 1994
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Remarks:
Clipped with electric clippers
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 500 mg of test material was applied to the right flank.

NEGATIVE CONTROL
- The left flank remained untreated and served as a control.
Duration of treatment / exposure:
The test material was held in contact with the skin for a period of 4 hours.
Observation period:
The study was terminated on Day 4
Number of animals:
Three female rabbits were selected for the study.
Details on study design:
TEST SITE
- Area of exposure: The day before treatment, the dorsum and the flanks of each animal were closely clipped with electric clippers. Only animals with healthy intact skin at the time of treatment were used. The test material was applied to an area of skin of 6 cm^2 on the right flank of the animals. Approximately 1 mL of 0.9 % saline was used to moisten the test material to ensure good contact with the skin. The left flank remained untreated and served as a control.
- Type of wrap if used: The test material was covered by a hydrophilic gauze patch which was secured by a semi-occlusive hypoallergenic dressing.

REMOVAL OF TEST SUBSTANCE
- Washing: The residual test material was gently removed with water.
- Time after start of exposure: At the end of the 4-hour period.

OBSERVATION TIME POINTS
Animals were checked for moribundity and mortality twice daily throughout the study. Animals were examined at least once daily for clinical signs. The cutaneous reactions were evaluated 1, 24, 48 and 72 hours after the removal of the dressings. As there were no signs of irritation after 72 hours, the study was terminated on Day 4.
At the end of the study period, animals were sacrificed without necropsy.

SCORING SYSTEM:
The skin reactions to treatment were evaluated according to the following scoring system:
Erythema and eschar formation
0 = No erythema
1 = Very slight erythema (barely perceptible)
2 = Well-defined erythema
3 = Moderate to severe erythema
4 = Severe erythema (beet redness) to slight eschar formation (injuries in depth)

Oedema formation:
0 = No oedema
1 = Very slight oedema (barely perceptible)
2 = Slight oedema (edges of area well defined by definite raising)
3 = Moderate oedema (raised approximately 1 millimetre)
4 = Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure)
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No erythema and no oedema were observed at any time.
Other effects:
There were no mortalities during the study.
There were no clinical signs during the study.
Interpretation of results:
other: Not classified according to EU criteria.
Conclusions:
Under the conditions of this study, the test material did not produce positive criteria in any rabbit and was considered non-irritant to rabbit skin.
Executive summary:

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

The potential of the test material to induce skin irritation/corrosion was assessed after a single semi-occlusive application for four hours in a group of three female rabbits. 500 mg of test material was applied to closely clipped skin. All animals were observed daily and the skin reactions were scored 1, 24, 48 and 72 hours after removal of the patches.

No erythema and no oedema were observed at any time. There were no mortalities during the study and no clinical signs.

Under the conditions of this study, the test material did not produce positive criteria in any rabbit and was considered non-irritant to rabbit skin.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
27 February 1990 to 11 March 1990
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:
1981
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPP 81-5 (Acute Dermal Irritation)
Version / remarks:
1984
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: Two and one-half to three months of age on arrival. The rabbits were approximately three months old on the day of dosing.
- Weight at study initiation: Bodyweight on the day of dosing was within the range 2.08 - 2.43 kg.
- Housing: Individually housed in suspended stainless-steel cages mounted in mobile batteries. The cages measured 61 x 76 x 46 cm high and were fitted with perforated counter-sunk floor panels. A tray beneath the floor was lined with absorbent crepe paper which was changed regularly.
- Diet: ad libitum access to a commercially available standard pelleted rabbit diet.
- Water: ad libitum access to tap water supplied to each cage by an automatic piped system. The water was supplied by the East Anglian Water Company.
- Acclimation period: Each animal was inspected on arrival and unsuitable individuals were rejected. Individual bodyweight was recorded on the day of arrival and at regular intervals thereafter. An acclimatisation period of at least six days was allowed between arrival at the laboratory and administration of the test material. During this time, the health status of each animal was monitored and a record kept. This record was consulted before an animal was allocated to study.

ENVIRONMENTAL CONDITIONS
- Temperature: Target value for temperature was 18 °C (range 15 - 23 °C)
- Humidity: Target value for humidity was 55 % R.H. (range 40 - 70 % R.H.)
- Air changes: Approximately 15 complete air changes per hour without re-circulation
- Photoperiod: 12 hours of artificial light per day
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Remarks:
Chemical depilatories were not used.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 g test material

NEGATIVE CONTROL
- The right test site on each animal acted as an untreated control

POSITIVE CONTROL
- None
Duration of treatment / exposure:
Four-hour exposure period
Observation period:
14 days
Number of animals:
Six male rabbits
Details on study design:
TEST SITE
- Area of exposure: The dorsum between the limb girdles. Each animal was examined for abnormality or irritation of the dermal test site before allocation to study. Two test sites (6 x 6 cm) were marked on either side of the clipped area of dorsum and moistened by direct application of approximately 0.2 mL distilled water per test site. A single dose (0.5 g) was applied directly to the skin.
- Type of wrap if used: The test site was covered by an unmedicated gauze patch (3 x 2 cm) which was held in place on the left test site by strips of medical tape. The right test site, acting as a control, was covered by a similar semi-occlusive dressing but otherwise remained untreated. Pads of cotton wool and elasticated bandage were used to protect the patches and ensure good contact between the skin and the test material. The elasticated bandage was held in place by thin strips of waterproof plaster at both edges.

REMOVAL OF TEST SUBSTANCE
- Washing: Where necessary, the treatment sites were gently washed with warm water and dried with paper towels to remove excessive amounts of test material adhering to the skin.
- Time after start of exposure: The dressings were removed after four hours of exposure.

OBSERVATION TIME POINTS
Assessment of skin irritation responses at the control and treated test sites were made one hour, 24, 48 and 72 hours after removal of the dressings. Additional observations of persistent effects of treatment were made on Days 7, 10 and 13.

SCORING SYSTEM:
Erythema and eschar formation
0 = No erythema
1 = Very slight erythema (barely perceptible)
2 = Well-defined erythema
3 = Moderate to severe erythema
4 = Severe erythema (beet redness) to slight eschar formation (injury in depth)

Oedema
0 = No oedema
1 = Very slight oedema (barely perceptible)
2 = Slight oedema (edges of area well-defined by definite raising)
3 = Moderate oedema (raised approximately 1 mm)
4 = Severe oedema (raised more than l mm and extending beyond the area of exposure)
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 13 days (exfoliation was observed on days 7 and 10)
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 13 days (exfoliation was observed on day 7)
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 13 days (exfoliation was observed on days 7 and 10)
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Very slight or, occasionally, slight erythema was observed at the test sites of five rabbits until the 1 hour, 24 hour, 72 hour, Day 7 or Day 10 examinations. Three of these animals also showed exfoliation on Day 7 and/or Day 10. The test sites of all rabbits were overtly normal on Day 13.
The control sites did not show any response to the control procedure.
Interpretation of results:
other: Not classified according to EU criteria.
Conclusions:
Under the conditions of this study, the test material was determined to be not irritating in accordance with EU criteria.
Executive summary:

The skin irritation potential of the test material was assessed in accordance with the standardised guidelines OECD 404 and US EPA OPP 81-5 under GLP conditions.

The potential of the test material to cause inflammatory or corrosive changes upon first contact with skin was assessed by semi-occluded application of 0.5 g of the test material to the closely-clipped dorsa of six New Zealand White rabbits for four hours. Dermal reactions were assessed 1, 24, 48 and 72 hours after removal of the dressings and on Days 7, 10 and 13.

Very slight or, occasionally, slight erythema was observed at test sites of five rabbits until the 1 h, 24 h, 72 h, Day 7 or Day 10 examinations. Three of these animals also showed exfoliation on Day 7 and/or Day 10. The test sites of all rabbits were overtly normal on Day 13.

Under the conditions of this study, the test material was determined to be not irritating in accordance with EU criteria.

Endpoint:
skin corrosion: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Justification for type of information:
An in vitro skin irritation/corrosion study does not need to be conducted because adequate data from in vivo skin irritation studies are available.
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:
key study
Study period:
24 January 1990 to 22 March 1990
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:
1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPP 81-4 (Acute Eye Irritation)
Version / remarks:
1984
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: Two and one-half to three months of age on arrival. The rabbit was approximately three months old on the day of dosing.
- Weight at study initiation: Bodyweight on the day of dosing was 2.79 kg.
- Housing: Individually housed in suspended stainless-steel cage mounted in mobile batteries. The cage measured 61 x 76 x 46 cm high and was fitted with perforated counter-sunk floor panels. A tray beneath the floor was lined with absorbent crepe paper which was changed regularly.
- Diet: ad libitum access to a commercially available standard pelleted rabbit diet.
- Water: ad libitum access to tap water supplied to each cage by an automatic piped system. The water was supplied by the East Anglian Water Company.
- Acclimation period: An acclimatisation period of at least seven days was allowed before administration of the test material. During this time the health status of the animal was monitored and a record kept. This record was consulted before the animal was allocated to study.

ENVIRONMENTAL CONDITIONS
- Temperature: Target value for temperature was 18 °C (range 15 - 23 °C)
- Humidity: Target value for humidity was 55 % R.H. (range 40 - 70 % R.H.)
- Air changes: Approximately 15 complete air changes per hour without re-circulation
- Photoperiod: 12 hours of artificial light per day
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 g of the test material
Duration of treatment / exposure:
Single exposure
Observation period (in vivo):
The animal was sacrificed by intravenous injection of sodium pentobarbitone B.Vet.C immediately after the 72 hour examination.
Number of animals or in vitro replicates:
One acclimatised male rabbit was used on this study.
Details on study design:
- Both eyes of the animal were examined before administration of the test material for signs of pre-existing irritation, reaction or abnormality which would prevent it from being used on the study.
- Bodyweight was recorded for the animal on the day of receipt and at regular intervals thereafter, until the rabbit began treatment.
- The dose was instilled into the right eye by pulling the lower eyelid away from the eyeball to form a cup into which 0.1 g of the test material was dropped. The eyelid was gently held together for one second and then released. The left eye remained untreated.
- The behaviour of the rabbit was observed for several minutes immediately following instillation of the test material to allow assessment of the initial pain response
- The animal was returned to its cage and checked at least twice during the first hour after dosing and at regular intervals throughout the day to ensure no severe injury passed un-noticed. Ocular reactions to treatment were assessed one hour, 24, 48 and 72 hours after treatment.
- The untreated eye was used as a comparison with the treated eye during assessment of ocular lesions.
- The animal was checked daily to ensure the treated eye was not subject to infection or causing distress.

REMOVAL OF TEST SUBSTANCE
The test material was not removed.

SCORING SYSTEM:
Cornea
0 = No opacity
1 = Scattered or diffuse areas of opacity, (other than slight dulling of normal lustre) details of iris clearly visible
2 = Easily discernible translucent areas, details of iris slightly obscured
3 = Nacreous areas, no details of iris visible, size of pupil barely discernible
4 = Complete corneal opacity, iris not discernible
The presence or absence of ulceration or stippling of the cornea was designated by + (positive) or - (negative). Redness of the cornea such as pannus formation is described on an individual basis.

Iris
0 = Normal
1 = Markedly deepened folds, congestion, swelling, moderate circumcorneal injection (any of these or any combination of them), iris still reacting to light (sluggish reaction is positive)
2 = No reaction to light, haemorrhage, gross destruction (any or all of these)

Conjunctivae: Redness (refers to palpebral and bulbar conjunctivae)
0 = Vessels normal
1 = Some vessels definitely injected
2 = Diffuse, crimson-red, individual vessels not easily discernible
3 = Diffuse beefy-red

Chemosis (lids and/or nictitating membrane)
0 = No swelling
1 = Any swelling above normal (including nictitating membrane)
2 = Obvious swelling with partial eversion of lids
3 = Swelling with lids about half-closed
4 = Swelling with lids more than half-closed
The presence or absence of necrosis or ulceration of the conjunctiva was designated by + (positive) or - (negative).

TOOL USED TO ASSESS SCORE:
- An ophthalmoscope was used to facilitate inspection of the eyes.
- The presence of corneal lesions was confirmed by fluorescein treatment. One drop of Fluorescein Sodium B.P. (Smith and Nephew Limited) was dropped directly onto the cornea. The rabbit was allowed to blink before excess fluorescein was flushed out of the eye with physiological saline. Corneal damage was confirmed by distinctive yellow colouration of any injured areas when viewed under ultra-violet illumination.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
2
Reversibility:
not specified
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not specified
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
not specified
Remarks on result:
positive indication of irritation
Irritant / corrosive response data:
- Injection of the conjunctival blood vessels, a diffuse crimson-red and a beefy-red appearance to the conjunctiva, very slight and slight chemosis and slight and moderate discharge with mucus were apparent during the 72 hour observation period.
- Slight opacity covering the entire cornea was observed one hour after instillation and was accompanied by two discrete areas of severe opacity (total of approximately half of the area of the cornea) at the 24, 48 and 72 hour examinations.
- Iridial congestion was apparent at the 72 hour examination.
- Due to the severity of the reaction, the animal was humanely killed following the 72 hour examination. No further animals were committed to the study.
- Instillation of the test material caused very slight initial pain response.
Interpretation of results:
other: Classified according to EU criteria as Category 1
Conclusions:
Under the conditions of this study the test material was considered to be 'severely irritant' with irreversible effects to the eye.
Executive summary:

The eye irritation potential of the test material was assessed according to the standardised guidelines OECD 405 and US EPE OPP 81-4 and in compliance with GLP.

The potential of the test material to cause damage to the conjunctiva, iris or cornea was assessed in one New Zealand White rabbit subjected to a single ocular instillation of 0.1 g of the test material on Day 1. Ocular reactions were examined 1, 24, 48 and 72 hours after treatment.

Injection of the conjunctival blood vessels, conjunctival redness (diffuse and beefy-red appearance), slight chemosis and moderate discharge with mucus were apparent during the 72 hour observation period.

Slight opacity (covering the entire cornea) was observed one hour after instillation and was accompanied by two discrete areas of severe opacity (total of approximately half of the area of the cornea) at the 24, 48 and 72 hour examinations. Iridial congestion was apparent at the 72 hour examination. Due to the severity of the reaction, the animal was humanely killed following the 72 hour examination. No further animals were committed to the study.

Instillation of the test material caused very slight initial pain response.

Under the conditions of this study the test material was considered to be 'severely irritant' with irreversible effects to the eye.

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Justification for type of information:
An in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin Irritation In Vivo: Dange (1994)

The skin irritation potential of the test material was assessed 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).

The potential of the test material to induce skin irritation/corrosion was assessed after a single semi-occlusive application for four hours in a group of three female rabbits. 500 mg of test material was applied to closely clipped skin. All animals were observed daily and the skin reactions were scored 1, 24, 48 and 72 hours after removal of the patches.

No erythema and no oedema were observed at any time. There were no mortalities during the study and no clinical signs.

Under the conditions of this study, the test material did not produce positive criteria in any rabbit and was considered non-irritant to rabbit skin.

Skin Irritation Supporting Study: Smith (1990)

The skin irritation potential of the test material was assessed in accordance with the standardised guidelines OECD 404 and US EPA OPP 81-5 under GLP conditions. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

The potential of the test material to cause inflammatory or corrosive changes upon first contact with skin was assessed by semi-occluded application of 0.5 g of the test material to the closely-clipped dorsa of six New Zealand White rabbits for four hours. Dermal reactions were assessed 1, 24, 48 and 72 hours after removal of the dressings and on Days 7, 10 and 13.

Very slight or, occasionally, slight erythema was observed at test sites of five rabbits until the 1 h, 24 h, 72 h, Day 7 or Day 10 examinations. Three of these animals also showed exfoliation on Day 7 and/or Day 10. The test sites of all rabbits were overtly normal on Day 13.

Under the conditions of this study, the test material was determined to be not irritating in accordance with EU criteria.

Eye irritation In Vivo: Smith (1990)

The eye irritation potential of the test material was assessed according to the standardised guidelines OECD 405 and US EPE OPP 81-4 and in compliance with GLP. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

The potential of the test material to cause damage to the conjunctiva, iris or cornea was assessed in one New Zealand White rabbit subjected to a single ocular instillation of 0.1 g of the test material on Day 1. Ocular reactions were examined 1, 24, 48 and 72 hours after treatment.

Injection of the conjunctival blood vessels, conjunctival redness (diffuse and beefy-red appearance), slight chemosis and moderate discharge with mucus were apparent during the 72 hour observation period.

Slight opacity (covering the entire cornea) was observed one hour after instillation and was accompanied by two discrete areas of severe opacity (total of approximately half of the area of the cornea) at the 24, 48 and 72 hour examinations. Iridial congestion was apparent at the 72 hour examination. Due to the severity of the reaction, the animal was humanely killed following the 72 hour examination. No further animals were committed to the study.

Instillation of the test material caused very slight initial pain response.

Under the conditions of this study the test material was considered to be 'severely irritant' with irreversible effects to the eye.

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 require classification with respect to eye irritation (Category 1, H318: Causes serious eye damage).

The substance does not require classification with respect to skin irritation.