Registration Dossier

Administrative data

Description of key information

Effects on skin irritation/corrosion:slightly irritating. However, not sufficient for classification under GHS

Effects on eye irritation:moderately irritating. However, not sufficient for classification under GHS

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:
2003-05-22 to 2003-05-25
Reliability:
1 (reliable without restriction)
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
New Zealand Albino, one male 2 female young adults. They were housed singly. Temperature 20-22 C with 12/12 hour light/dark cycle.
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 mL to 6cm2 per animal
Duration of treatment / exposure:
After 4 hours the pads and collars were removed and the test sites cleansed of any residue substance
Observation period:
1, 24, 48 and 72 hours after removal of patch
Number of animals:
3
Details on study design:
Individual dose sites were scored according to the Draize scoring system. The classification of irritancy was obtained by adding the average erythema and edema scores for the 1, 24, 48 and 72-hour scoring intervals and dividing by the number of evaluation intervals (4). The resulting Primary Dermal Irritation Index (PDII) was classified as follows:
0 - Non-irritiating
>0-2.0 - Slightly irritating
2.1-5.0 - Moderately irritating
>5.0 - Severely irritating
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 1
Score:
1
Max. score:
1
Reversibility:
no data
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24
Score:
1
Max. score:
1
Reversibility:
no data
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48
Score:
0
Max. score:
1
Reversibility:
no data
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72
Score:
0
Max. score:
1
Reversibility:
no data
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 1
Score:
0
Max. score:
1
Reversibility:
no data
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24
Score:
0
Max. score:
1
Reversibility:
no data
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 48
Score:
0
Max. score:
1
Reversibility:
no data
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72
Score:
0
Max. score:
1
Reversibility:
no data
Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: Primary Dermal Irritation Index
Conclusions:
Under the conditions of this study, the test substance is classified as slightly irrritating to the skin.
Executive summary:

3 New Zealand Albino rabbits had 0.5mL of the test substance topically applied to a clipped 6cm2 area of skin which was then covered semi-occlusively for 4 hours. No edema was noted for any treated site during the study.

At one and 24 hours after the patch removal slight erythema was evident at all 3 treated sites in all animals. All animals were free from dermal irritation at 48 hours. The Primary Dermal Irritation Index was 0.5. Under the conditions of this study, the test substance is classified as slightly irrritating to the skin.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (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:
2003-05-29 to 2003-06-01
Reliability:
1 (reliable without restriction)
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
New Zealand Albino, three male young adults. They were housed singly. Temperature 18-22 C with 12/12 hour light/dark cycle
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.1 mL was instilled into the conjunctival sac of the right eye of 3 healthy rabbits by pulling the lower lid way from the eyeball. The upper and lower lids were then gently held together for about one second before releasing to minimise loss of the test subtsance. The left eye remained untreated and served as a control.
Duration of treatment / exposure:
72 hours
Observation period (in vivo):
1, 24, 48 and 72 hours
Number of animals or in vitro replicates:
3
Details on study design:
Ocular irritation was evaluated using a high-intensity white ligh in accordance with Draize et al. at 1, 24, 48 and 72 hours post-installation. The time interval with the highest mean score (Maximum Mean Total Score - MMTS) for all rabbits was used to classify the test substance by the system of Kay and Calandra.
Irritation parameter:
maximum mean total score (MMTS)
Basis:
animal #1
Time point:
72 h
Score:
13.3
Max. score:
110
Reversibility:
fully reversible within: 72h
Remarks on result:
probability of mild irritation
Irritation parameter:
maximum mean total score (MMTS)
Basis:
animal #2
Time point:
72 h
Score:
13.3
Max. score:
110
Reversibility:
fully reversible within: 72h
Remarks on result:
probability of mild irritation
Irritation parameter:
maximum mean total score (MMTS)
Basis:
animal #3
Time point:
72 h
Score:
13.3
Max. score:
110
Reversibility:
fully reversible within: 72h
Remarks on result:
probability of mild irritation

   
   
   
   
   
  Incidence of Irritation
 Time Post Instillation (Hours)  Corneal Opacity  Iritis  Conjunctivitis
 1  0/3  0/3  3/3
 24  0/3  0/3  3/3
 48  0/3  0/3  3/3
 72  0/3  0/3  0/3

 Time Post Instillation (Hours)  Severity of Irritation - Mean Score
 1  13.3
 24  10.0
 48  4.0
 72  0.0
 
Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: not specified
Executive summary:

0.1 mL of the test substance was instilled into the right eye of 3 healthy rabbits by pulling the lower lid way from the eyeball. The upper and lower lids were then gently held together for about one second before releasing to minimise loss of the test subtsance. The left eye served as a control. Occular irritation was evaluated by the Draize et al. method. Ocular irritation was evaluated using a high-intensity white ligh in accordance with Draize et al. at 1, 24, 48 and 72 hours post-installation. The time interval with the highest mean score (Maximum Mean Total Score - MMTS) for all rabbits was used to classify the test substance by the system of Kay and Calandra.

All animals appeared active and healthy. Apart from the eye irritation described below, there were no signs of gross toxicity, adverse phamacologic effects or abnormal behaviour.

No corneal opacity ot iritis was noted for any treated eye during the study. One hour after test substance installation, all three treated eyes exhibited conjunctivitis. The overall severity of irritation decreased with time. All animals were free of occular irritiation within 72 hours.

The Maximum Mean Total Score was 13.3 and is therefore classified as mildly irritating to the eye under these study conditions.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Effects on skin irritation/corrosion: slightly irritating. However, not sufficient for classification under GHS

Effects on eye irritation: moderately irritating. However, not sufficient for classification under GHS

Justification for classification or non-classification

Effects on skin irritation/corrosion:slightly irritating. However, not sufficient for classification under GHS

Effects on eye irritation:moderately irritating. However, not sufficient for classification under GHS