Registration Dossier

Administrative data

Description of key information

Skin irritation: not irritating (OECD 404, GLP);

Eye irritation: not irritating (OECD 405, GLP)

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:
2006-07-24 to 2006-08-24
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
2002-04-24
Deviations:
yes
Remarks:
The temperature range was 16 - 20 °C instead of 17 - 20 °C. The test site of the initial animal was only immediately examined after the 3-minute and one-hour exposure and not after the four hour exposure.
GLP compliance:
yes (incl. QA statement)
Remarks:
signed 2005-06-01
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature in the dark, desiccated, under inert gas
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Highgate Farm, Market Rasen, Lincolnshire, England
- Age at study initiation: At least 26 weeks of age
- Weight at study initiation: Weight range of 4.10 to 4.47 kg
- Housing: The rabbits were housed individually in plastic cages with perforated floors
- Diet: Each rabbit was offered 125 g of a standard laboratory rabbit diet (Rabbit GD Diet Pellets supplied by Highgate Farm) per day. The animals were given a dietary supplement of hay.
- Water (ad libitum): Drinking water
- Acclimation period: At least 14 weeks prior to the start of the study.
During the acclimatisation and study period the animals were given small soft white untreated wood blocks for environmental enrichment.

ENVIRONMENTAL CONDITIONS
- Temperature: 16 to 20°C
- Relative humidity: 40 to 70%
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The treatment site was ‘wetted’ with 0.5 mL of reverse osmosis water and approximately 0.5 g of the test
substance was applied.
Duration of treatment / exposure:
One animal (acted as a preliminary screen): three minutes, one or four hour exposure
Two additional animals: 4 hour exposure
Observation period:
Examination of the treated skin was made on removal of the dressings (for 3 minute or one hour exposures) and approximately 1, 24, 48 and 72 hours later.
Number of animals:
3 male rabbits
Details on study design:
A single animal received three exposures (of three minutes, one or four hours duration) in a step-wise manner and acted as a preliminary screen. In the absence of a severe effect on removal of the dressings the next exposure was initiated.
Two additional animals were treated with the test item for four hours.

TEST SITE
On the day before application of the test substance, hair was removed with clippers from the dorso-lumbar region of each rabbit exposing an appropriate sized area of skin. The treatment site was ‘wetted’ with the vehicle and the test substance was applied under a 2-ply 25 mm x 25 mm porous gauze pad secured with ‘blenderm’ surgical tape to intact skin sites on three animals. An additional site was similarly treated with the exception of test substance and acted as a control.
For exposures of one hour or more each treatment site was covered with cotton wool and "Tubigrip" elasticated bandage dressing for the duration of the exposure period. The animals were returned to their cages immediately after treatment.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Treatment site was washed with lukewarm water (30-40°C) to remove any residual test substance. The treated area was blotted dry with absorbent paper.
- Time after start of exposure: At the end of the exposure period

SCORING SYSTEM: Draize scoring system

OBSERVATIONS:
Clinical signs: All animals were observed daily for signs of ill health or toxicity.
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
No dermal reaction was observed in any animal throughout the duration of the study.
Other effects:
There was no sign of toxicity or ill health in any rabbit during the observation period.
Interpretation of results:
GHS criteria not met
Conclusions:
The test item is not irritating to the skin.
According to the Regulation (EC) No 1272/2008 and subsequent regulations, the test item is not classified as 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:
2006-09-15 to 2006-09-26
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
2002-04-24
Deviations:
yes
Remarks:
The temperature range was 16 - 20 °C instead of 17 - 20 °C.
GLP compliance:
yes (incl. QA statement)
Remarks:
signed 2005-06-01
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature in the dark, desiccated, under inert gas
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Highgate Farm, Market Rasen, Lincolnshire, England
- Age at study initiation: Approximately 31 to 36 weeks of age
- Weight at study initiation: Weight range of 4.70 to 5.52 kg
- Housing: The rabbits were housed individually in plastic cages with perforated floors.
- Diet: Each rabbit was offered 125 g of a standard laboratory rabbit diet (Rabbit GD Diet Pellets supplied by Highgate Farm) per day. The animals were given a dietary supplement of hay up to 48 hours before dosing.
- Water (ad libitum): Drinking water
- Acclimation period: At least ten weeks prior to the start of the study
During the acclimatisation and study period the animals were given small soft white untreated wood blocks for environmental enrichment.

ENVIRONMENTAL CONDITIONS
- Temperature: 16 to 20 °C
- Relative humidity: 40 to 70 %
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit):0.1 ml of the test substance, weighing approximately 85 mg, was instilled into the right eye by pulling the lower eyelid away from the eye ball to form a cup into which the test substance was dropped. The eyelids were then gently held together for one second before releasing; the left eye remained untreated. The untreated eye was used as a comparison with the treated eye during assessment of ocular lesions.
Duration of treatment / exposure:
Not applicable
Observation period (in vivo):
Ocular reactions to treatment were assessed 1, 24, 48 and 72 hours after treatment.
Number of animals or in vitro replicates:
3 female rabbits
Details on study design:
The eyes of each animal were examined prior to instillation of the test substance to ensure that there was no pre-existing corneal damage, iridial inflammation or conjunctival irritation. A sentinel animal was used in this study with two additional animals.

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: An ophthalmoscope or pencil beam torch was available for use to facilitate inspection of the eyes.

OBSERVATIONS:
Clinical signs: The behaviour of each rabbit was observed immediately following instillation of the test substance to allow assessment of the initial pain response (for criteria for assessment of pain response see "Any other information on materials and methods incl. tables" below).
The animals were checked at least twice during the first hour after dosing and at regular intervals throughout the day to ensure no severe injury passed unnoticed.
No further information on the study design was stated.
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: Slight initial pain was observed in this animal.
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: Slight initial pain was observed in this animal.
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: Slight initial pain was observed in this animal.
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
Injection of the conjunctival blood vessels was apparent in all animals during the first 24 hours after instillation persisting in one case until the 48 hour observation. Slight discharge was also evident one hour after instillation.
The treated eye of each animal was overtly normal 72 hours after instillation.
Instillation of the test substance gave rise to slight initial pain response.
Other effects:
Clinical signs:
There was no sign of toxicity or ill health in any rabbit during the observation period.
Interpretation of results:
GHS criteria not met
Conclusions:
The test item is not irritating to the eyes.
According to the Regulation (EC) No 1272/2008 and subsequent regulations, the test item is not classified as eye irritant.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Skin irritation

The substance was not observed to be irritating to the skin in a reliable in vivo skin irritation study according to OECD 404.

Eye irritation:

The substance was not observed to be irritating to the eye in a reliable in vivo eye irritation study according to OECD 405.

Justification for classification or non-classification

Skin irritation

The substance does not possess an skin irritating potential based on an in vivo OECD 404 (2002) test and does not require classification as skin irritating according to Regulation (EC) No 1272/2008 and its subsequent adaptations.

Eye irritation:

The substance does not possess an eye irritation potential according to an in vivo OECD 405 (2002) test and does not require classification as eye irritant according to Regulation (EC) No 1272/2008 and its subsequent adaptations.