Registration Dossier

Toxicological information

Skin irritation / corrosion

Currently viewing:

Some information in this page has been claimed confidential.

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
4th May 1993 to 18th May 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OTS 798.4470 (Acute Dermal Irritation)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: Young adult
- Weight at study initiation: 4421 to 5333 grams
- Housing: Individual suspended mesh bottom cages
- Diet:ad libitum
- Water: tap water ad libitum
- Acclimation period: a minimum of 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24 °C
- Humidity (%): 42-76 %
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
14 days
Number of animals:
6 females
Details on study design:
TEST SITE
- Area of exposure: Back
- Type of wrap if used: Each sample was applied under a 2.5 cm² gauze patch that was overwrapped with a gauze binder and secured with tape. Plastic restraint collars were applied and remained on the animals for the duration of exposure.

REMOVAL OF TEST SUBSTANCE
At the end of the exposure period, the test site was wiped with paper towels moistened with mineral oil (USP).

OBSERVATION TIME POINTS
The rabbits were observed at 1, 24, 48 and 72 hours after partch removal and daily thereafter through day 14 if irritation persisted.

SCORING SYSTEM:
- Method of calculation: Draize
Erythema and Eschar Formation
No erythema – 0
Very slight erythema (barely perceptible, edges of area not well defined) – 1
Slight erythema (pale red in colour) – 2
Moderate to severe erythema (definite red in colour and area well defined) – 3
Severe erythema (beet or crimson red) to slight eschar formation (injuries in depth) – 4
Oedema formation
No Oedema – 0
Very slight oedema (barely perceptible, edges of area not well defined) – 1
Slight oedema (edges of area well defined by definite raising) – 2
Moderate oedema (raised approximately 1 mm) – 3
Severe oedema (raised more than 1 mm and sever oedema extending beyond area of exposure) - 4

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 10 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 12 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 11 days
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
fully reversible within: 12 days
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 12 days
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
The test material induced slight to moderate erythema on all rabbits and very slight to slight oedeman in four rabbits. Desquamation was presented on all sites by day 7. All oedema completely subsided by day 9 or earlier. Minor reversible (grade 1) erythema on one site and desquamation on four sites persisted through study termination.
Other effects:
There were no unscheduled deaths during the course of the study.
There were no significant effects on body weight changes during the study (animals were weighed on day 0 and at study termination).

Any other information on results incl. tables

Table 1: Results

 

Animal

Observation

1 hour

24 hours

48 hours

72 hours

4 days

5 days

6 days

7 days

8 days

9 days

10 days

11 days

12 days

13 days

14 days

1

Erythema

2

3

3

3

3

3d

2d

2d

1d

1d

1d

1d

1d

1d

1d

Oedema

0

1

1

1

2

2

1

1

1

0

0

0

0

0

0

2

Erythema

2

2

2

2

2d

2d

2d

1d

1d

1d

0d

0d

0d

0

-

Oedema

0

1

0

0

0

0

0

0

0

0

0

0

0

0

-

3

Erythema

2

3

3

3

3

3d

2d

2d

2d

1d

1d

1d

0d

0d

0d

Oedema

0

1

1

1

1

1

1

0

0

0

0

0

0

0

0

4

Erythema

2

2

2

2

2

2

1

1d

1d

1d

1d

0d

0d

0d

0d

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

5

Erythema

2

3

2

3

3d

3d

3d

2d

2d

1d

1d

1d

0d

0d

0d

Oedema

1

1

1

1

2

2

1

1

0

0

0

0

0

0

0

6

Erythema

2

2

2

2

2

2d

1d

1d

1d

1d

1d

1d

0d

0

-

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

-

d = desquamation
- = animal terminated from study, irritation previously subsided.

 

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test material induced slight to moderate erythema on all rabbits. Four sites had very slight to slight oedema. Desquamation was present on all sites by the end of the first week of the study. In general erythema and oedema had completely subsided by day 12 or earlier with the exception of one animal where very slight erythema persisted to day 14. Four animals had desquamation at study termination. The primary irritation index was calculated as 2.8 which equates to the description of moderately irritating, however in accordance with the criteria outlined in Regulation EC 1272/2008 (CLP), the test material is not classified.
Executive summary:

The skin irritation of the test material was investigated in female albino rabbits in accordance with OECD 404, EU Method B.4 and EPA OTS 798.4470. The test material induced slight to moderate erythema on all rabbits. Four sites had very slight to slight oedema. Desquamation was present on all sites by the end of the first week of the study. In general erythema and oedema had completely subsided by day 12 or earlier with the exception of one animal where very slight erythema persisted to day 14. Four animals had desquamation at study termination.  The primary irritation index was calculated as 2.8 which equates to the description of moderately irritating, however in accordance with the criteria outlined in Regulation EC 1272/2008 (CLP), the test material is not classified (the test material induced a positive response in 3/6 animals).