Registration Dossier

Administrative data

Description of key information

The eye irritating potential of the test item was assessed according to OECD TG 405. Three rabbits were exposed to 0.1 mg test item. The mean score was calculated across three scoring times (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris, redness and chemosis of the conjunctivae, separately. The individual mean scores for corneal opacity and iris were 0.00 for all three animals.

The individual mean scores for the conjunctivae were 0.00, 0.00 and 0.33 for reddening and 0.00, 0.00 and 0.67 for chemosis for all animals, respectively.One hour after instillation all treated animals showed slight conjunctival redness (score 1) and one animal showed also slight chemosis (score 1).All effects were fully reversible within 72 h.

The eye irritating potential of the test item was assessed according to OECD TG 405. Three rabbits were exposed to 0.1 mg test item. The mean score was calculated across three scoring times (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris, redness and chemosis of the conjunctivae, separately. The individual mean scores for corneal opacity and iris were 0.00 for all three animals.

The individual mean scores for the conjunctivae were 0.00, 0.00 and 0.33 for reddening and 0.00, 0.00 and 0.67 for chemosis for all animals, respectively.One hour after instillation all treated animals showed slight conjunctival redness (score 1) and one animal showed also slight chemosis (score 1).All effects were fully reversible within 72 h.

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:
From 31 AUG 1999 to 09 SEP 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
17 JUL 1992
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
31 JUL 1992
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elevage Scientifique des Dombres, F-01400 Chatillon sur Chalaronne, France
- Age at study initiation: male: 13 weeks, females 14-15 weeks
- Weight on day of treatment: male 2467 g, females 2937 and 2583 g
- Housing: Individually in stainless steel cages equipped with feed hoppers, drinking water bowls, with wood and haysticks
- Diet: Pelleted standard Provimi Kliba 3418 rabbit maintainance diet, ad libitum, haysticks provided by Eberle Nafag AG, CH-9200 Gossau
- Water: Community tap water, ad libitum
- Acclimation period: yes

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+- 3
- Humidity (%): 40-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied : 0.5 g/animal, moistened with bi-distilled water
Duration of treatment / exposure:
4 h
Observation period:
72 h
Number of animals:
1 male, 2 females
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: substance applied on surgical gauze patch, covered with semi-occlusive dressing, wrapped around the abdomen and anchored with tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with lukewarm tap water
- Time after start of exposure: 4 h, at the end of exposure time

OBSERVATION TIME POINTS
1, 24, 48 and 72 h after removal of the test substance

SCORING SYSTEM:
- Method of calculation: The skin reactionwas assessed according to the numerical scoring system listed in the EEC Commission Directive 92/69/EEc, July 31, 1992.
The primary irritation score was calculated by totalling the individual cummulative scores at 24, 48 and 72 h and then dividing by the number of data points.
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No corrosive or irriating effects observed.

No clinical signs of systemic toxicity were observed in the animals during the test and observation period, and no mortality ocurred.

Yellow stainig of the treated skin was observed.

Interpretation of results:
GHS criteria not met
Conclusions:
The test item did not reveal any irritation potential on the skin of rabbits, tested in this study according to OECD test guideline no. 404 and GLP conditions.
Executive summary:

The skin irritating potential of the test item was assessed according to OECD TG 404. Three rabbits (1 male and 2 females) were exposed to 0.5 mg test item under semi-occlusive conditions for 4 hours. Yellow staining produced by the colour of the test item on the treated skin was observed in all animals at the 1-hour reading and persisted up to the 48- or 72-hour reading. The test item did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0). The individual mean score for erythema/eschar and oedema for each of the three animals was therefore 0.

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:
From 07 SEP 1999 to 16 SEP 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
24 FEB 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
31 JUL 1992
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Elevage Scientifique des Dombres, F-01400 Chatillon sur Chalaronne, France
- Age at study initiation: females 14 weeks, males 15 weeks
- Weight at study initiation: male 2601 g, females 2548 and 2826 g
- Housing: Individually in stainless steel cages equipped with feed hoppers, drinking water bowls, with wood and haysticks
- Diet: Pelleted standard Provimi Kliba 3418 rabbit maintainance diet, ad libitum, haysticks provided by Eberle Nafag AG, CH-9200 Gossau
- Water: Community tap water, ad libitum
- Acclimation period: yes

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+- 3
- Humidity (%): 40-70
- Air changes (per hr): 10-15
- 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 g/animal
Duration of treatment / exposure:
test substance was not removed from the eye
Observation period (in vivo):
72 h
Number of animals or in vitro replicates:
1 male, 2 females
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

SCORING SYSTEM: The occular reaction was assessed according to the numerical scoring system listed in the EEC Commission Directive 92/69/EEC, July 32, 1992.

TOOL USED TO ASSESS SCORE: Varta Cliptrix diagnostic lamp
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal: #1 and #2
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
animal: #1 and #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritant / corrosive response data:
Slightly reddened conjunctivae was observed in all three animals 1 h after application. The effect remained in one animal at the 24 hour reading, but was fully reversible within 48 h.
One hour after instillation one animal showed also slight chemosis (score 1).
Other effects:
No clinical signs of systemic toxicity were observed in the animals during the test and observation period, and no mortalities ocurred. Yellow remnants in eye or conjunctival sac and around eye and /or on lids by the test article were observed.
Interpretation of results:
GHS criteria not met
Conclusions:
The test item did not induce significant or irreversible damage to the rabbit eye in this study according to OECD test guideline no. 405 and GLP conditions.
Executive summary:

The eye irritating potential of the test item was assessed according to OECD TG 405. Three rabbits were exposed to 0.1 mg test item. The mean score was calculated across three scoring times (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris, redness and chemosis of the conjunctivae, separately. The individual mean scores for corneal opacity and iris were 0.00 for all three animals.

The individual mean scores for the conjunctivae were 0.00, 0.00 and 0.33 for reddening and 0.00, 0.00 and 0.67 for chemosis for all animals, respectively. One hour after instillation all treated animals showed slight conjunctival redness (score 1) and one animal showed also slight chemosis (score 1). All effects were fully reversible within 72 h.

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

No classification

Neither on skin nor on eyes of rabbits in vivo relevant signs of irritation were recorded