Registration Dossier

Administrative data

Description of key information

Three rabbits were dermally treated with the substance during 4 hours. Slight irritation of the skin was seen during the 72 hour observation period. The effects were fully reversible at 72 hours. The substance is not irritating to the skin (Safepharm 2005).

Three rabbits received 96 mg of the substance in the eye. Very slight irritation was seen 1 hour after installation. At the other observations (until 72 hours after instillation) no signs of irritation were found. The substance is not irritating to the eyes (Safepharm 2005).

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:
21 July 2005 to 24 July 2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study according to the guidelines under GLP
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire UK
- Age at study initiation: 12-20 weeks
- Weight at study initiation: 2.0 to 3.5 kg
- Housing: individually
- Diet: Certified Rabbit Diet (Code 5322) from BCM IPS Ltd, London UK ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C
- Humidity (%): 30-70%
- Air changes (per hr): ≥15/hr
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Remarks:
moistened with 0.5 mL of distilled water
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
Duration of treatment / exposure:
4 hours
Observation period:
72 hours (observations at 1, 24, 48 and 72 hours after removal of the dressing)
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: 2.5x 2.5 cm2
- Type of wrap if used: cotton gauze patch

REMOVAL OF TEST SUBSTANCE
- Washing (if done): swab with cotton wool soaked in distilled water
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24-72 h
Score:
0.67
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24-72 h
Score:
0.44
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Other effects:
Blue staining of the application site at all timepoints

Animal

1

2

3

Time

erythema

oedema

erythema

oedema

erythema

oedema

1

0

0

0

0

0

0

24

1

1

1

1

1

1

48

1

1

1

0

1

0

72

0

0

0

0

0

0

Interpretation of results:
GHS criteria not met
Conclusions:
The substance is not irritating to the skin
Executive summary:

Three rabbits were dermally treated with the substance during 4 hours. Slight irritation of the skin was seen during the 72 hour observation period. The effects were fully reversible at 72 hours. The substance is not irritating to the skin.

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:
25 July 2005 to 04 August 2005
Reliability:
1 (reliable without restriction)
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire UK
- Age at study initiation: 12-20 weeks
- Weight at study initiation: 2.0 to 3.5 kg
- Housing: individually
- Diet: Certified Rabbit Diet (Code 5322) from BCM IPS Ltd, London UK ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C
- Humidity (%): 30-70%
- Air changes (per hr): ≥15/hr
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml (96 mg)
Duration of treatment / exposure:
single instillation (eyelids were hold for 1 second)
Observation period (in vivo):
72 hours (observations at 1, 24, 48 and 72 hours after instillation)
Number of animals or in vitro replicates:
3 males
Details on study design:
First one animal was treated. After consideration of the ocular responses of this animal 2 additional animals were treated

REMOVAL OF TEST SUBSTANCE
- Washing (if done): none

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: ophthalmoscope
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Max. score:
1
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Max. score:
0
Other effects:
Black staining of the fur arround the treated eye was observed at all timepoints

Animal no 1       2       3      
Time 1 24 48 72 1 24 48 72 1 24 48 72
cornea  0 0 0 0 0 0 0 0 0 0 0 0
iris 0 0 0 0 0 0 0 0 0 0 0 0
conjunctivae                        
redness 1 0 0 0 1 0 0 0 1 0 0 0
chemosis 0 0 0 0 0 0 0 0 0 0 0 0
discharge 0 0 0 0 0 0 0 0 0 0 0 0
Interpretation of results:
GHS criteria not met
Conclusions:
The substance is not irritating to the eyes
Executive summary:

Three rabbits received 96 mg of the substance in the eye. Very slight irritation was seen 1 hour after installation. At the other observations (until 72 hours after instillation) no signs of irritation were found. The substance is not irritating to the eyes.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Based on the outcome of the available studies, the substance does not need classification for skin and eye irritation according to EC No 1272/2008 (CLP Regulation)