Registration Dossier

Administrative data

Description of key information

Skin irritation (similar to OECD TG 404): not irritating
Eye irritation and severe damage (similar to OECD TG 405): not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation / corrosion, other
Remarks:
See at justification for type of information
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1977-03-11
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study is considered to be a reliability 2 since it predates GLP but is similar to OECD TG 404.
Justification for type of information:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available [study scientifically not necessary / other information available]
Reference:
Composition 1
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
no
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
not specified
Preparation of test site:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
other: The untreated skin of each animal served as controls.
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 mL
Duration of treatment / exposure:
24 hours
Observation period:
14 days
Number of animals:
6 animals
Details on study design:
REMOVAL OF TEST SUBSTANCE
24 hours after the application.

OBSERVATIONS
The skin reactions were assessed at approximately 4, 24, 48, 72 and 168 hours after exposure to the test substance. The irritation scores and a description of all other (local) effects were recorded.

SCORING SYSTEM:
The irritation was assessed according to the numerical scoring system according to OECD 404 (1981)
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours (mean)
Score:
1.55
Max. score:
4
Reversibility:
fully reversible
Remarks:
within 7 days
Remarks on result:
other: average scores 24h, 48h and 72h were 1.67, 1.50, and 1.50, respectively
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours (mean)
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: average scores 24h, 48h and 72h were 1.00, 0, and 0, respectively
Other effects:
Defatting effect, skin sloughed off in ten to fourteen days. There was no injury in depth.

Skin irritation response data (for the undiluted test substance)

 

Time after administration

 

4 hour

24 hours

48 hours

72 hours

Animal

1

2

3

4

5

6

1

2

3

4

5

6

1

2

3

4

5

6

1

2

3

4

5

6

Erythema

1

1

1

1

1

1

2

2

2

2

1

1

2

1

2

2

1

1

2

1

2

2

1

1

Edema

0

0

0

0

0

0

1

1

1

1

1

1

0

0

0

0

0

0

0

0

0

0

0

0

Interpretation of results:
other: not irritating
Remarks:
According to CLP Regulation (EC) 1272/2008
Conclusions:
In a skin irritation study with rabbits, performed similar to OECD 404 (1981), mild irritation was observed, which was fully reversible within 7 days. Based on the results of this study, the substance is considered to be not irritating to skin for CLP. The substance also does not need to be classified according to GHS because only 3/6 animals reached score 2 over 24, 48 and 72hours, while for classification 4/6 animals should have > 2 erythema or oedema score.
Executive summary:

The substance was tested a in a skin irritation test similar to the OECD TG 404 test guideline. 6 New Zealand White rabbits were exposed for 24 hours to the undiluted test substance. The mean value for erythema from gradings at 24, 48 and 72 hours after patch removal was 1.55. For edema, this mean value was 0.33. No corrosive effects were observed. The irritation was fully reversible within 7 days. The substance is not considered to be irritating to skin, according to EU CLP criteria.

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:
1977-03-11
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study is considered to be a reliability 2 since it predates GLP but is similar to OECD TG 405.
Justification for type of information:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Reference:
Composition 1
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Controls:
other: One eye of each animal remained untreated and served as the reference control.
Amount / concentration applied:
Amount applied: 0.1 mL
Duration of treatment / exposure:
Single instillation on Day 1
Observation period (in vivo):
at least one week
Number of animals or in vitro replicates:
6 animals
Details on study design:
STUDY DESIGN
The test material was applied undiluted in 6 animals.

TREATMENT
Similar to OECD 405. The test substance is placed in the conjunctival sac of one eye of each animal after gently pulling the lower lid away from the eyeball. The lids are then gently held together for about one second. The other eye serves at control.

OBSERVATIONS
The eyes of each animal were examined approximately 1, 24, 48 and 72 hours and 5, and 7 days after instillation of the test substance. The irritation scores and a description of all other (local) effects were recorded.

SCORING SYSTEM:
Eye irritation was scored according to Draize at al., 1944.
Cornea score: Opacity (max score 4) x Area of cornea involved (max score 4) x 5 = maximum score of 80
Iris score: iris lesion (max score 2) x 5 = maximum score of 10
Conjunctiva score: (Redness (max score 3) + Chemosis (max score 4) + Discharge (max score 3) x 2 = maximum score of 20
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: mean 24, 48, and 72 hours
Score:
1.67
Max. score:
80
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Score according to Draize et al., 1944. average scores 24h, 48h and 72h were 5, 0, and 0, respectively
Irritation parameter:
iris score
Basis:
mean
Time point:
other: mean 24, 48, and 72 hours
Score:
0
Max. score:
10
Remarks on result:
other: Score according to Draize et al., 1944
Irritation parameter:
conjunctivae score
Remarks:
redness, chemosis and discharge
Basis:
mean
Time point:
other: mean 24, 48, and 72 hours
Score:
4.33
Max. score:
20
Reversibility:
fully reversible within: 5 days
Remarks on result:
other: Score according to Draize et al., 1944. average scores 24h, 48h and 72h were 8.67, 2.33, and 2, respectively
Irritant / corrosive response data:
Immediate: discomfort was moderate with eyes tightly closed.
10 min: Slight erythema, copious discharges.
1 hr.: Slight erythema, copious discharges.
24 hr.: Areas of barely perceptible corneal dullness, slight to moderate erythema, copious discharge.
48-72 hr.:Gradual improvement.
120 hr.: All scored zero.

Ocular Irritant response data (for the undiluted test substance)

 

Time after administration

 

1 hour

24 hours

48 hours

72 hours

Animal

1

2

3

4

5

6

1

2

3

4

5

6

1

2

3

4

5

6

1

2

3

4

5

6

Cornea score

0

0

0

0

0

0

5

5

5

5

5

5

0

0

0

0

0

0

0

0

0

0

0

0

Iris score

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Conjunctivae score (redness, chemosis and discharge

8

8

8

8

8

8

10

10

8

8

8

8

4

2

2

2

2

2

2

2

2

2

2

2

Interpretation of results:
other: not irritating
Remarks:
according to CLP Regulation (EC) 1272/2008
Conclusions:
In a skin irritation study with rabbits, performed similar to OECD 404, slight irritation was observed, which was fully reversible within 5 days. Based on the results of this study, the substance is considered to be not irritating to skin
Executive summary:

The substance was tested in an eye irritation test similar to OECD 405. 0.1 mL undiluted test substance was placed in the conjuctival sac of 6 new Zealand white rabbits. The effects were scored 1, 24, 48, 72, 120, and 168 hours after application according to Draize et al., 1944. No effects on the iris were observed. The cornea score was 5 out of 80 for all animals at the 24 hour time point and was fully reversible within 48 hours. The conjunctivae scores after 24h, 48h and 72h were 8.67, 2.33, and 2 out of 20, respectively. The effects on the conjunctivae were reversible within 5 days. Under the conditions of the test, the substance is not eye irritating.

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

Additional information

Skin irritation:

The substance was tested a in a skin irritation test similar to the OECD TG 404 test guideline. 6 New Zealand White rabbits were exposed for 24 hours to the undiluted test substance. The mean value for erythema from gradings at 24, 48 and 72 hours after patch removal was 1.55. For edema, this mean value was 0.33. No corrosive effects were observed. The irritation was fully reversible within 7 days. The substance is not considered to be irritating to skin, according to EU CLP criteria.

Eye irritation:

The substance was tested in an eye irritation test similar to OECD 405. 0.1 mL undiluted test substance was placed in the conjuctival sac of 6 new Zealand white rabbits. The effects were scored 1, 24, 48, 72, 120, and 168 hours after application according to Draize et al., 1944. No effects on the iris were observed. The cornea score was 5 out of 80 for all animals at the 24 hour time point and was fully reversible within 48 hours. The conjunctivae scores after 24, 48 and 72h were 8.67, 2.33, and 2 out of 20, respectively. The effects on the conjunctivae were reversible within 5 days. Under the conditions of the test, the substance is not eye irritating.

Justification for classification or non-classification

Based on the negative results in the skin and eye irritation tests the substance does not need to be classified for this endpoint according to EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.