Registration Dossier

Administrative data

Description of key information

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:
1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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
Species:
rabbit
Strain:
Vienna White
Details on test animals and environmental conditions:
TEST ANIMALS

- Source: Gaukler, Offenbach/Main, Germany
- Age at study initiation: young adult animals
- Weight at study initiation: males: 2.4 and 2.61 kg; female: 2.45 kg
- Housing: single
- Diet: Kliba 341, 4 mm; Klingentalmühle AG, Switzerland; ca. 130 g/animal/day
- Water: ca. 250 mL tap water/animal/day
- Acclimation period: at least 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 12. Feb. 1990 To: 14. Feb 1990
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Remarks:
moistened with water to form a paste
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.5 g
Duration of treatment / exposure:
4 h
Observation period:
72 h; Readings: 30 to 60 min after removal of the patch and 24 h, 48 h, and 72 h after the beginning of applikation
Check for mortality: every work day and once on Saturdays, Sundays and public holidays.
Number of animals:
3 (2 males and 1 female)
Details on study design:
Application
The test substance was applied in a single dose to the intact untreated skin. The test patch was secured in position with a semi occlusive dressing; the test substance was removed at the end of the exposure period with Lutrol and Lutrol/water (1:1).

Clipping of the fur: At least 24 hours before the test, the fur was removed by clipping the dorsal part of the trunk of the animals. Only animals with healthy intact skin have been used.
Application site: upper third of the back or flanks.
Negative control: Untreated skin sites of the same animal.
Application volume: The test patch (2.5 cm x 2.5 cm) was covered with dose of 0.5 g of the unchanged solid test substance and has been moistened with aqua bidest (because of the natural moisture of the skin, distilled water was used so that the test has been carried out under as physiological conditions as possible).

Irritation parameter:
erythema score
Basis:
animal: #1 and #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 72 h
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
Interpretation of results:
GHS criteria not met
Conclusions:
Under the study conditions, the test substance was not irritating to skin.
Executive summary:

A study was conducted to determine the skin irritation/corrosion potential of the test substance in Vienna White rabbits according to OECD Guideline 404 and EU Method B.4, in compliance with GLP.

0.5 g of the unchanged test substance was applied in a single dose to the intact untreated skin of the 3 New Zealand rabbits for 4 h. The test patch was secured in position with a semi-occlusive dressing and the test substance was removed at the end of the exposure period with Lutrol and Lutrol/water (1:1). The average score (24, 48, and 72 h) for irritation was calculated to be 0.0 in 2 and 0.3 in one rabbit for erythema and 0.0 for edema. The skin findings were reversible within 72 h, thus the study was terminated after 72 h. Under the study conditions, the test substance was not irritating to 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:
1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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
Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS

- Source: Gaukler, Offenbach/Main, Germany
- Age at study initiation: young adult animals
- Weight at study initiation: male: 2.3 kg; females: 2.41 and 2.48 kg
- Housing: single
- Diet: Kliba 341, 4 mm; Klingentalmühle AG, Switzerland; ca. 130 g/animal/day
- Water: ca. 250 mL tap water/animal/day
- Acclimation period: at least 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 12. Feb. 1990 To: 27. Feb 1990
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 mL bulk volume (about 69 mg of the comminuted test substance)
Duration of treatment / exposure:
24 h
Observation period (in vivo):
15 d. Readings: 1h, 24h, 48h, 72h, 8d, 15d. A check for mortality was made twice each workday and once on Saturday, Sunday or public holidays.
Number of animals or in vitro replicates:
3 ( 1 male and 2 females)
Details on study design:
The test substance was applied in a single dose to the conjunctival sac of the right eyelid. The substance was not washed out.
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:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 8 d
Remarks on result:
probability of weak irritation
Irritation parameter:
conjunctivae score
Basis:
animal: #1 and #2
Time point:
24/48/72 h
Score:
2.33
Max. score:
3
Reversibility:
fully reversible within: 15 d
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.33
Max. score:
3
Reversibility:
fully reversible within: 8 d
Remarks on result:
probability of weak irritation
Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Under the study conditions, the test substance caused irritation to the conjunctiva of 2 rabbits with a score >= 2. All effects were reversible within the 15 days observation period
Executive summary:

A study was conducted to determine the eye irritation/corrosion potential of the test substance in White Vienna rabbits according to OECD Guideline 405 and EU Method B.5, in compliance with GLP.

0.1 mL of the test substance (about 69 mg) was applied in a single dose to the conjunctival sac of the right eyelid of each animal. The substance was not washed out. The untreated eye served as negative control. Readings were taken at 1, 24, 48, 72h, then 8 and 15 d. The average score (24, 48, 72 h) for irritation was calculated to be 0.0 for corneal opacity and iris. The index for chemosis was 1.33 in all three rabbits; conjunctival redness was 2.33 in 2 animals and 1.33 in one rabbit. The findings were reversible in all animals within 8 or 15, days of application. Under the study conditions, the test substance caused conjunctival reddening in 2 rabbits with a score of >=2 and has hence to be classified as irritating to eyes.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin

A study was conducted to determine the skin irritation/corrosion potential of the test substance in Vienna White rabbits according to OECD Guideline 404 and EU Method B.4, in compliance with GLP.

0.5 g of the unchanged test substance was applied in a single dose to the intact untreated skin of the 3 New Zealand rabbits for 4 h. The test patch was secured in position with a semi-occlusive dressing and the test substance was removed at the end of the exposure period with Lutrol and Lutrol/water (1:1). The average score (24, 48, and 72 h) for irritation was calculated to be 0.0 in 2 and 0.3 in one rabbit for erythema and 0.0 for edema. The skin findings were reversible within 72 h, thus the study was terminated after 72 h. Under the study conditions, the test substance was not irritating to skin.

Eyes

A study was conducted to determine the eye irritation/corrosion potential of the test substance in White Vienna rabbits according to OECD Guideline 405 and EU Method B.5, in compliance with GLP.

0.1 mL of the test substance (about 69 mg) was applied in a single dose to the conjunctival sac of the right eyelid of each animal. The substance was not washed out. The untreated eye served as negative control. Readings were taken at 1, 24, 48, 72h, then 8 and 15 d. The average score (24, 48, 72 h) for irritation was calculated to be 0.0 for corneal opacity and iris. The index for chemosis was 1.33 in all three rabbits; conjunctival redness was 2.33 in 2 animals and 1.33 in one rabbit. The findings were reversible in all animals within 8 or 15, days of application. Under the study conditions, the test substance caused conjunctival reddening in 2 rabbits with a score of >=2 and has hence to be classified as irritating to eyes.

Justification for classification or non-classification

Based on the results of in vivo studies in rabbits, the test substance is classified as Cat 2 eye irritant according to CLP (EC 1272/2008) criteria.