Registration Dossier

Administrative data

Description of key information

Skin irritation: Key study. Method according to Draize (1944), similar to OECD 404 (no GLP). Under test conditions, the test item was not irritating to the skin of rabbits (irritation score = 0.0).

Eye irritation: Key study. Method according to Draize (1944), similar to OECD Guideline 405 (no GLP). Under test conditions, the test substance was found to be non-irritating to the eyes (72h irritation score = 0).

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:
1978.
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
application to intact and to abraded skin, 24h exposure, occlusive wrapping, area 25 cm2.
Principles of method if other than guideline:
- Method according to Draize JH, Woodward G, Calvery HO (1944). Methods for the Study of Irritation and Toxicity of Substances Applied Topically to the Skin and Mucous Membranes, Journal of Pharmacology and Experimental Therapeutics November 1, 1944, 82 (3) 377-390 (see 'Attached background material').
GLP compliance:
no
Test material information:
Composition 1
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Neo-DHC, Lot #26-RS-17, received date 8/11/78.
- Purity (HPLC): 98.5%
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Six albino New Zealand rabbits (3 males, 3 females), each abraded and non-abraded, no further details.
Type of coverage:
occlusive
Preparation of test site:
other:
Remarks:
clipped or abraded.
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
0.5mL
Duration of treatment / exposure:
24h.
Observation period:
72h.
Number of animals:
6 (3 males, 3 females)
Details on study design:
TEST SITE
Test performed on clipped and also on abraded skin areas. Applications were made under occlusive patches; following application of the test material the entire trunk of each animal was covered with an impermeable occlusive wrapping. The animals were then immobilised.
- Area of exposure: 2x2in (~25cm2).
- Type of wrap if used: gauze covered by adhesive tape.

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24h

OBSERVATION TIME POINTS
- 24 and 72h.

SCORING SYSTEM:
- Draize test criteria.
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24h
Score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 72h
Score:
0
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
- The test item is not a primary dermal irritant to rabbits under the conditions of this test.
- Combined Averages = 0.0.
- Primary Irritation Index = 0.0.

Table 1. Dermal Irritation scores.

Rabbit

Skin

E (24h)

Ed (24h)

E (72h)

E (72h)

Total Score

1

NA

0

0

0

0

0

A

0

0

0

0

0

2

NA

0

0

0

0

0

A

0

0

0

0

0

3

NA

0

0

0

0

0

A

0

0

0

0

0

4

NA

0

0

0

0

0

A

0

0

0

0

0

5

NA

0

0

0

0

0

A

0

0

0

0

0

6

NA

0

0

0

0

0

A

0

0

0

0

0

Avg

NA

0

0

0

0

0

A

0

0

0

0

0

E/Ed: Erythema and Edema, NA: non-abraded skin, A: abraded skin.

 

Interpretation of results:
GHS criteria not met
Remarks:
EU criteria.
Conclusions:
Under test conditions, the test substance was found to be non-irritating.
Executive summary:

A study was performed on the test item to investigate its possible irritation or corrosion on rabbits, according to the method of Draize (1944), similar to OECD Guideline 404 (no GLP). Six New Zealand White rabbits (3 males, 3 females) were applied 0.5 ml of test item on 2"x2" clipped (intact) or abraded areas of skin, covered with occlusive dressing during 24h. Then, the wrapping and the test item were removed, and the sites were individually examined and scored for erythema and edema at 24 and 72h. The mean values were used to determine the final irritation indices. Under test conditions, the test item was found to be non-irritating to the skin (irritation score = 0.0).

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:
1978.
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
0.1mL dose, treated eyes unwashed for 24h, 7d observation period.
Principles of method if other than guideline:
The procedure followed was a modification of that used by Dr. J.H. Draize in Appraisal of The Safety of Chemicals in Foods, Drugs and Cosmetics, compiled by the staff of the Division of Pharmacology, Food and Drug Administration - Department of Health, Education and Welfare.
GLP compliance:
no
Test material information:
Composition 1
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Neo-DHC, Lot #26-RS-17, received date 8/11/78.
- Purity (HPLC): 98.5%
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Six albino New Zealand rabbits (3 males, 3 females), healthy, without ocular defects; no further details.
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
0.1mL
Duration of treatment / exposure:
24h.
Observation period (in vivo):
7d.
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: water rinsing.
- Time after start of exposure: 24h.

SCORING SYSTEM: Observations of injuries were made on the cornea, iris and the bulbar and palpebral conjunctivae. Numerical scores were assigned to lesions observed according to the Draize standard scoring system. In this system, the injuries to the cornea and iris account for approximately 80% of the total score; these structures are purposely weighted because of their vital role in the vision. The maximum score is the sum of all scores obtained for the cornea, iris, and conjunctivae.

TOOL USED TO ASSESS SCORE: hand-held lenses.
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
24 h
Score:
2.2
Max. score:
110
Reversibility:
fully reversible within: 2d
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
72 h
Score:
0
Max. score:
110
Remarks on result:
no indication of irritation
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
7 d
Score:
0
Max. score:
110
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
See table 1.

Table 1. Eye Irritation

Rabbit

Day

Cornea

A x B x 5

Iris

C x 5

Conjunctivae

(D + E + F) x 2

Total Score

1

1

0

0

0

0

0

0

0

2

0

0

0

0

0

0

0

3

0

0

0

0

0

0

0

4

-

-

-

-

-

-

-

7

-

-

-

-

-

-

-

2

1

0

0

0

0

0

0

0

2

0

0

0

0

0

0

0

3

0

0

0

0

0

0

0

4

-

-

-

-

-

-

-

7

-

-

-

-

-

-

-

3

1

0

0

1

1

1

1

11

2

0

0

0

1

0

0

2

3

0

0

0

0

0

0

0

4

-

-

-

-

-

-

-

7

-

-

-

-

-

-

-

 4

1

0

0

0

0

0

0

0

2

0

0

0

0

0

0

0

3

0

0

0

0

0

0

0

4

-

-

-

-

-

-

-

7

-

-

-

-

-

-

-

5

1

0

0

0

1

0

0

2

2

0

0

0

0

0

0

0

3

0

0

0

0

0

0

0

4

-

-

-

-

-

-

-

7

-

-

-

-

-

-

-

6

1

0

0

0

0

0

0

0

2

0

0

0

0

0

0

0

3

0

0

0

0

0

0

0

4

-

-

-

-

-

-

-

7

-

-

-

-

-

-

-

Average

1

*total score possible = 110

2.2

2

0.3

3

0.0

4

-

7

-

A: opacity, B: area of cornea involved, C: value, D: redness, E: chemosis, F: discharge.

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under test conditions, the test substance is found to be not irritating.
Executive summary:

A study to investigate possible irritation or corrosion of the test substance on the eyes of rabbits was performed according to Draize (1944), similar to OECD Guideline 405 (no GLP). The right eye of 6 New Zealand White rabbits (3 males, 3 females) received single application of 0.1ml test item, while the left eye was used as a control. The treated eyes of all rabbits remained unwashed for 24h, readings were made using hand-held lenses 1, 2, 3 and up to 7 days after. Under test conditions, the test substance was found to be non-irritating to the eyes.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

- Skin irritation: Key study. Method according to Draize (1944), similar to OECD 404 (no GLP). Six New Zealand White rabbits were applied 0.5 ml of test item on 2"x2" clipped or abraded areas of skin, covered with occlusive dressing during 24h. Then, the wrapping and the test item were removed, and the sites were individually examined and scored for erythema and edema at 24 and 72h. The test item was not irritating to the skin (irritation score = 0.0).

- Eye irritation: Key study. Method according to Draize (1944), similar to OECD Guideline 405 (no GLP). The right eye of 6 New Zealand White rabbits (3 males, 3 females) received single application of 0.1ml test item, while the left eye was used as a control. The treated eyes of all rabbits remained unwashed for 24h, readings were made using hand-held lenses 1, 2, 3 and up to 7 days after. Under test conditions, the test substance was found to be non-irritating to the eyes (72h irritation score = 0).

Justification for classification or non-classification

Skin irritation: Based on available data (irritation score 0 in vivo), the substance is not classified for skin irritation/corrosion according to CLP Regulation (EC) No. 1272/2008.

Eye irritation: Based on available data (irritation score 0 in vivo), the substance is not classified as causing serious eye damage according to CLP Regulation (EC) No. 1272/2008.