Registration Dossier

Toxicological information

Eye irritation

Currently viewing:

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Cross-reference
Reason / purpose for cross-reference:
reference to same study
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Analytical purity of test substance not specified, occlusive dressing according to former guideline, 24 h exposure time, test substance was not removed after exposure
GLP compliance:
no
Species:
rabbit
Strain:
Himalayan
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Own breeding
- Weight at study initiation: 2.16 - 2.45 kg
- Housing: Separated in single cages
- Diet: Standard diet ERKA 8300 (Robert Koch oHG, Hamm, Germany), ad libitum
- Water: ad libitum
Type of coverage:
occlusive
Preparation of test site:
other: 6 x 3 cm, one half shaved the other additionally abraded
Vehicle:
other: Polyethylenglycol 400
Controls:
not specified
Amount / concentration applied:
500 mg in 1.2 mL vehicle on 2.5 x 2.5 cm
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg
- Concentration: 500 mg moistened with 1.2 ml polyethyleneglycol 400

VEHICLE
- Amount(s) applied (volume or weight with unit): 1.2 ml
Duration of treatment / exposure:
24 h
Observation period:
Examinations after 24, 48 and 72 h
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: shaved flank
- Type of wrap if used: Moistened test material was applied to 2.5 x 2.5 cm cellulose pads from Hansamed, the pads were fixed to the prepared application site and covered with an indifferent, impermeable polyethylene film (6 - 8 cm width). Subsequently, the whole trunk of the animals was wrapped with an elastic polyurethan warp bandage (permanent bandage K, Lohmann) left in place for 24 h.

REMOVAL OF TEST SUBSTANCE
- Washing: no

SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Reversibility: not applicable
Remarks on result:
other: intact skin
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Reversibility: not applicable
Remarks on result:
other: intact skin
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Reversibility: not applicable
Remarks on result:
other: intact skin
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Reversibility: not applicable
Remarks on result:
other: intact skin
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Reversibility: not applicable
Remarks on result:
other: intact skin
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Reversibility: not applicable
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Reversibility: not applicable
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Reversibility: not applicable
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Reversibility: not applicable
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Reversibility: not applicable
Remarks on result:
other: intact skin
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: intact skin
Irritant / corrosive response data:
No erythema was observed in abraded skin, either. Edema of grade 1 was observed in 4/6 animals in abraded skin after 24 h which was fully reversible after 48 h.
Other effects:
No mortality occurred. There were no clinical signs of systemic toxicity from the dermal exposure.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Executive summary:

The test substance is not irritating and does not have to be classified according to the criteria of Regulation (EC) No. 1272/2008.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report date:
1981

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
only 72 h observation time, no informations on full reversibility
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
N,N'-ethylenedi(stearamide)
EC Number:
203-755-6
EC Name:
N,N'-ethylenedi(stearamide)
Cas Number:
110-30-5
Molecular formula:
C38H76N2O2
IUPAC Name:
N,N'-ethane-1,2-diyldioctadecanamide
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder

Test animals / tissue source

Species:
rabbit
Strain:
Himalayan
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Own breeding
- Weight at study initiation: 2.02 - 2.59 kg
- Housing: Separated in single cages
- Diet: Standard diet ERKA 8300 (Robert Koch oHG, Hamm, Germany), ad libitum
- Water: ad libitum

Test system

Vehicle:
other: Polyethylene glycol 400
Controls:
other: right eye served as untreated control
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 100 mg, moistened with 0.4 mL vehicle

VEHICLE
- Amount applied: 0.4 mL
Duration of treatment / exposure:
24 h
Observation period (in vivo):
1, 7, 24, 48 and 72 h
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: physiol. saline
- Time after start of exposure: 24 h

SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: hand lens, additionally at 48 and 72 h timepoints: one drop of fluorescein 0.01 %

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2, #4 - #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Reversibility: not applicable
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 72 h (end of observation period)
Irritation parameter:
iris score
Basis:
animal: #1 - #6
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: Reversibility: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal: #1, #2
Time point:
24/48/72 h
Score:
0.66
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
not fully reversible within: 72 h (end of observation period)
Irritation parameter:
conjunctivae score
Basis:
animal: #4, #5
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
other: Reversibility: not applicable
Irritation parameter:
chemosis score
Basis:
animal: #1 to #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Reversibility: not applicable
Irritant / corrosive response data:
Although there is slight redness and corneal opacity left in 1/6 animals after 72 hours, the decrease of the scores over the observation time and the slight characteristics of the observations make it reasonable to anticipate full reversibility after a slightly longer observation period.

Any other information on results incl. tables

Table 1: Eye irritation scores after 1 and 7 h

 

1 h

7 h

Rabbit No.

1

2

3

4

5

6

1

2

3

4

5

6

Cornea score

0

1

0

0

0

0

0

0

1

0

0

0

Iris score

0

0

0

0

0

0

0

0

0

0

0

0

Cojunctiva score

2

2

2

2

2

2

2

2

2

2

2

1

Chemosis score

2

2

2

2

2

2

1

1

1

1

1

1

Discharge score

3

3

3

3

2

3

2

1

1

1

0

1

Table 2: Eye irritation scores after 24, 48 and 72 h

 

24 h

48 h

72 h

Rabbit No.

1

2

3

4

5

6

1

2

3

4

5

6

1

2

3

4

5

6

Cornea score

0

0

1

0

0

0

0

0

1

0

0

0

0

0

1

0

0

0

Iris score

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Cojunctiva score

1

1

1

2

2

0

1

1

1

1

1

0

0

0

1

0

0

0

Chemosis score

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Discharge score

1

1

2

1

0

1

0

0

0

0

0

0

0

0

0

0

0

0

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Executive summary:

Although there is slight redness and corneal opacity left in one animal after 72 h, the decrease of the scores over the observation time and the slight characteristics of the observations make it reasonable to anticipate full reversibility after a slightly longer observation period. Therefore, the substance does not have to be classified according to the criteria of Regulation (EC) No. 1272/2008.