Registration Dossier

Administrative data

Description of key information

Based on the available data, the test substance is considered irritating to both the skin and eyes.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
other: Title 21, Code of Federal Regulations, 191.11.
GLP compliance:
not specified
Species:
rabbit
Strain:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Housing: Screen bottom cages
- Diet (e.g. ad libitum): Laboratory chow, ad libitum
- Water (e.g. ad libitum): ad libitum
Type of coverage:
semiocclusive
Preparation of test site:
other: one abraded area and one intact area
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
0.5 mL (0.5 g) of the 100% concentration of the test substance.
Duration of treatment / exposure:
24 h
Observation period:
24 and 72 h
Number of animals:
Six
Details on study design:
TEST SITE
- Area of exposure: Backs and flanks of the animals were clipped hair free
- Test substance application: 0.5 mL (0.5 g) of the undiluted test substance was applied in an occlusive patch to the abraded and intact areas of the skin, covered with gauze patch by adhesive-tape.
Duration: 24 h
Scoring criteria: According to Draize classification.
Observations: at 24 and 72 h.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 and 72 h
Score:
5.5
Max. score:
8
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: PDII equals average of 24 and 72 h
Irritation parameter:
erythema score
Basis:
animal: 1 to 6
Time point:
24 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: similar results for abraded and non-abraded skin
Irritation parameter:
edema score
Basis:
animal: 1 to 6
Time point:
24 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: similar results for abraded and non-abraded skin
Irritation parameter:
erythema score
Basis:
animal: 1 to 6
Time point:
48 h
Remarks on result:
not measured/tested
Irritation parameter:
erythema score
Basis:
animal: 1 to 6
Time point:
72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: similar results for abraded and non-abraded skin
Irritation parameter:
edema score
Basis:
animal: 1 to 6
Time point:
72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 72 h
Remarks on result:
other: similar results for abraded and non-abraded skin
Irritation parameter:
edema score
Basis:
animal: 1 to 6
Time point:
48 h
Remarks on result:
not measured/tested
Other effects:
None

Results for the primary skin irritation of the abraded and intact skin at 24 and 72 hrs:

Animal number

24 h

72 h

Abraded

Intact

Abraded

Intact

1

3-2

3-2

3-3

3-3

2

3-2

3-2

3-3

3-3

3

3-2

3-2

3-3

3-3

4

3-2

3-2

3-3

3-3

5

3-2

3-2

3-3

3-3

6

3-2

3-2

3-3

3-3

Scoring was done similar to the Draize system of classification.

Observations: Moderate to severe erythema and defined edema was observed at 24 h and moderate to severe erythema and moderate edema was observed at 72 h on abraded and intact rabbit skin.

The mean primary skin irritation index obtained = 5.50 (mean of erythema and edema scores at 24 and 72 h).

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
Under the conditions of the study, the test substance was irritating to skin.
Executive summary:

A study was conducted to assess the irritation potential of the test substance to rabbit skin in accordance with Title 21, Code of Federal Regulations, 191.11. Six animals were treated with undiluted test substance (0.5 mL or 0.5 g). The treated areas were covered with a semi-occlusive gauze patch and taped to maintain the test substance in contact with the skin for 24 h. The degree of erythema and edema was recorded according to the Draize scoring system after 24 and 72 h. Moderate to severe erythema and defined edema was observed at 24 h and moderate to severe erythema and moderate edema was observed at 72 h on the abraded and intact rabbit skin. The mean primary skin irritation index (PII) was 5.5. Under the conditions of the study, the test substance was irritating to skin (Casey, 1976).

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
other: Title 21, Code of Federal Regulations, 191.11.
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL or 0.1 g of the undiluted test substance was instilled into one eye of each rabbit. The other eye served as control.
- Concentration (if solution): 100% (undiluted)
Duration of treatment / exposure:
Single instillation
Observation period (in vivo):
24, 48, 72 h and 7 and 14 d.
Number of animals or in vitro replicates:
Six
Details on study design:
0.1 mL or 0.1 g of the undiluted test substance was instilled into the one eye of each animal, and the other eye served as control. The eyes were evaluated for damage to cornea, iris and bulbar and palpebral conjunctivae at 24, 48 and 72 h and 7 and 14 d after instillation. Any residue of the test substance and accumulated discharge are flushed from the eye each time they are scored.
Irritation parameter:
cornea opacity score
Basis:
animal: 1 to 6
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal: 1 to 6
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal: 1 to 6
Time point:
24/48/72 h
Score:
>= 1 - <= 2
Max. score:
2
Reversibility:
not fully reversible within: 14 d
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal: 1 to 6
Time point:
24/48/72 h
Score:
>= 1 - <= 2
Max. score:
2
Reversibility:
not fully reversible within: 14 d
Remarks on result:
positive indication of irritation
Irritation parameter:
overall irritation score
Remarks:
Undiluled test substance
Basis:
animal: 1 to 6
Time point:
24 h
Score:
11.33
Reversibility:
not fully reversible within: 14 d
Irritation parameter:
overall irritation score
Remarks:
Undiluted test substance
Basis:
animal: 1 to 6
Time point:
48 h
Score:
7.67
Reversibility:
not fully reversible within: 14 d
Irritation parameter:
overall irritation score
Remarks:
Undiluted test substance
Basis:
animal: 1 to 6
Time point:
72 h
Score:
5.67
Reversibility:
not fully reversible within: 14 d
Irritation parameter:
overall irritation score
Remarks:
Undiluted test substance
Basis:
animal: 1 to 6
Time point:
7 d
Score:
3.33
Reversibility:
not fully reversible within: 14 d
Irritation parameter:
overall irritation score
Remarks:
Undiluted test substance
Basis:
animal: 1 to 6
Time point:
14 d
Score:
2.33
Reversibility:
not fully reversible within: 14 d
Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Under the test conditions, the undiluted test substance can be assessed to be a irritating to eyes.
Executive summary:

The ocular irritation potential of the test substance was investigated using New Zealand white rabbits in accordance with Title 21, Code of Federal Regulations, 191.11. The substance (0.1 mL or 0.1 g) was instilled into one eye of each of six rabbits; the other eye served as control. The eyes were evaluated for damage to cornea, iris and conjunctivae at 24, 48, 72 h, then 7 and 14 d. Irritation response in the conjunctiva was observed in terms of redness, chemosis and discharge. The mean conjunctival redness score was 2 in 4/6 animals. The mean irritation score of 11.33, 7.67, 5.67, 3.33 and 2.33 was observed after 24, 48 and 72 h, then 7 and 14 d. Except for conjunctival redness, which was the most prominent response and was present in 3/6 animals, irritation in the remaining eye (chemosis and discharge) reduced to almost 0 by Day 14. Under the conditions of the study, the undiluted test substance was irritating to eyes (Casey, 1976).

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 assess the irritation potential of the test substance to rabbit skin in accordance with Title 21, Code of Federal Regulations, 191.11. Six animals were treated with undiluted test substance (0.5 mL or 0.5 g). The treated areas were covered with a semi-occlusive gauze patch and taped to maintain the test substance in contact with the skin for 24 h. The degree of erythema and edema was recorded according to the Draize scoring system after 24 and 72 h. Moderate to severe erythema and defined edema was observed at 24 h and moderate to severe erythema and moderate edema was observed at 72 h on the abraded and intact rabbit skin. The mean primary skin irritation index (PII) was 5.5. Under the conditions of the study, the test substance was irritating to skin (Casey, 1976).

Eye

The ocular irritation potential of the test substance was investigated using New Zealand white rabbits in accordance with Title 21, Code of Federal Regulations, 191.11. Undiluted substance (0.1 mL or 0.1 g) was instilled into one eye of each of six rabbits; the other eye served as control. The eyes were evaluated for damage to cornea, iris and conjunctivae at 24, 48, 72 h, then 7 and 14 d. Irritation response in the conjunctiva was observed in terms of redness, chemosis and discharge. The mean conjunctival redness score was 2 in 4/6 animals. The mean irritation score of 11.33, 7.67, 5.67, 3.33 and 2.33 was observed after 24, 48 and 72 h, then 7 and 14 d. Except for conjunctival redness, which was the most prominent response and was present in 3/6 animals, irritation in the remaining eye (chemosis and discharge) reduced to almost 0 by Day 14. Under the conditions of the study, the undiluted test substance was irritating to eyes (Casey, 1976).

The ocular irritation potential of diluted test substance was investigated using New Zealand white rabbits in accordance with Title 21, Code of Federal Regulations, 191.11. The substance (0.1 mL or 0.1 g of 5% test substance in distilled water) was instilled into one eye of each of six rabbits; the other eye served as control. The eyes were evaluated for damage to cornea, iris and conjunctivae at 24, 48 and 72 h. The mean irritation score of 1.0, 0.0 and 0.0 was observed after 24, 48 and 72 h. Under the conditions of the study, the 5% diluted test substance was non-irritating to eyes (Casey, 1976).

Justification for classification or non-classification

Skin

The available in vivo skin irritation study demonstrates a clear irritation response following semi-occlusive exposure to the test substance for 24 h. The data support a classification as Skin Irrit. 2 - H315 (causes skin irritation) according to CLP (EC 1272/2008) criteria.

Eye

The available in vivo eye irritation study with undiluted test substance showed irritation to rabbit eyes and supports classification as Eye Irrit. 2 – H319 (causes serious eye irritation) according to CLP (EC 1272/2008) criteria.