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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
13 - 20 Nov 1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
No information on purity was given. Observation period was only 7 days.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1981
Deviations:
yes
Remarks:
no data on test substance purity given, post-observation time not long enough to confirm supposed reversibility
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: approx. 12-16 weeks
- Weight at study initiation: 2.19-3.00 kg
- Housing: animals were housed individually in suspended metal cages
- Diet: Rabbit Diet (A.W. Tindall Limited, Holbeach, UK), ad libitum
- Water: tap water, ad libitum
- Acclimation period: minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-21
- Humidity (%): 45-50
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
other: unchanged (100% test substance) and absolute ethanol (25, 5 and 1% test substance)
Controls:
other: Untreated sites of the same animal served as control.
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 mL
- Concentration: 1, 5, 25 and 100%
Duration of treatment / exposure:
4 h
Observation period:
7 days
Reading time points: 1, 24, 48 and 72 h and 7 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: area on the back (four suitable test sites were selected)
- Type of wrap: The test substance was applied to the skin and covered with a patch which consisted of a 2.5 cm square of surgical gauze two layers thick. The loaded patch was held in contact with one of the selected test sites with two lengths of Sleek adhesive strapping (Smith & Nephew Limited) in the form of a cross. Additionally, the trunk was wrapped in an elasticated corset (TUBIGRIP).

REMOVAL OF TEST SUBSTANCE
- Washing: The skin was cleaned of residual test substance by gentle swabbing with cotton wool soaked in ether.
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize scoring system

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: mean after 24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: 100% test substance
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: mean after 24/48/72 h
Score:
2.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: 100% test substance
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: mean after 24/48/72 h
Score:
3.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: 100% test substance
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: mean after 24/48/72 h
Score:
4
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: 100% test substance
Irritant / corrosive response data:
100% test substance:
The test substance produced severe cutaneous irritation in all rabbits. Well-defined erythema with severe oedema extending beyond the treatment site was noted at all treated skin sites 1 h after removal of the patches. Moderate to severe erythema with slight to severe oedema extending beyond the test sites continued to be noted at all treated skin sites up to 72 h after treatment. Observation on Day 7 revealed very slight erythema in 2 animals. Hyperkeratinisation and desquamation was noted in all treated skin sites at this time.

25% test substance:
The test substance produced distinct cutaneous irritation in all rabbits. Well-defined erythema with slight to severe oedema extending beyond the test sites was noted at all treated skin sites 1 hour after removal of the patches. The erythema increased slightly at the 24-hour reading to show moderate to severe erythema at one treated site and well-defined erythema in a further two treated skin sites. The erythema continued and well-defined erythema was noted in 2/3 treated skin sites at the 72-hour observation; barely perceptible erythema was noted in the remaining test site. The oedema gradually regressed and very slight to slight oedema was noted in 2/3 treated skin sites at the 72-hour observation. Hyperkeratinisation was noted in 2/3 treated skin sites on Day.7. All test sites showed desquamation extending beyond the test site at this time.

5% test substance:
The test substance produced minimal cutaneous irritation in 3/3 rabbits. Barely perceptible erythema with minimal oedema was noted at all treated skin sites 1 h after removal of the patches. The erythema quickly regressed and all skin sites appeared normal at subsequent observations.

1% test substance:
The test substance produced minimal cutaneous irritation in 2/3 rabbits. Barely perceptible erythema with minimal oedema was noted at 2/3 treated skin sites 1 h after removal of the patches. The erythema quickly regressed and all skin sites appeared normal at subsequent observations.

Any other information on results incl. tables

Table 1. Results of the skin irritation study following 4 h exposure with undiluted test substance.

Observation time

Rabbit no.

1

2

3

Erythema

Edema

Erythema

Edema

Erythema

Edema

1 h

3

4

3

4

3

4

24 h

3

4

3

4

3

4

48 h

3

2

3

4

3

4

72 h

3

2

3

2

3

4

7 days

1HD

0

1HD

0

0HD

0

Mean value
24 + 48 + 72 h

3.0

2.7

3.0

3.3

3.0

4.0

H: hyperkeratinisation

D: desquamation

 

Table 2. Results of the skin irritation study following 4 h exposure with test substance at concentration of 25% (v/v) in absolute ethanol.

Observation time

Rabbit no.

1

2

3

Erythema

Edema

Erythema

Edema

Erythema

Edema

1 h

2

2

2

4

2

4

24 h

2

1

2

2

3

4

48 h

2

1

2

1

2

4

72 h

1

0

2

1

2

2

7 days

0D

0

0HD

0

0HD

0

Mean value
24 + 48 + 72 h

1.7

0.7

2.0

1.3

2.3

3.3

H: hyperkeratinisation

D: desquamation

Table 3. Results of the skin irritation study following 4 h exposure with test substance at concentration of 5% (v/v) in absolute ethanol.

Observation time

Rabbit no.

1

2

3

Erythema

Edema

Erythema

Edema

Erythema

Edema

1 h

1

0

1

1

1

0

24 h

0

0

0

0

0

0

48 h

0

0

0

0

0

0

72 h

0

0

0

0

0

0

7 days

0

0

0

0

0

0

Mean value
24 + 48 + 72 h

0

0

0

0

0

0

 

Table 4. Results of the skin irritation study following 4 h exposure with test substance at concentration of 1% (v/v) in absolute ethanol.

Observation time

Rabbit no.

1

2

3

Erythema

Edema

Erythema

Edema

Erythema

Edema

1 h

0

0

1

1

1

1

24 h

0

0

0

0

0

0

48 h

0

0

0

0

0

0

72 h

0

0

0

0

0

0

7 days

0

0

0

0

0

0

Mean value
24 + 48 + 72 h

0

0

0

0

0

0

Applicant's summary and conclusion

Interpretation of results:
other: Skin Irrit. Cat. 2 at 100% test substance
Remarks:
according to Regulation (EC) No 1272/2008
Conclusions:
Under the conditions of this skin irritation study in rabbits the test substance at concentration of 100% was irritating to the skin. Concentrations of 1, 5 and 25% of the test substance were considered not irritating to skin.
Executive summary:

A skin irritation study was performed according to OECD 404 and GLP. The primary irritation test in rabbits was performed at 1, 5, 25 and 100 % in Ethanol.

The mean values for 24-72 hours in 3 rabbits for 1% and 5% in Ethanol were all 0.0. The mean values in 3 rabbits for 25% in Ethanol were for erythema 1.7, 2.0 and 2.3, for edema 0.7, 1.3 and 3.3.

Mean values for the pure test item at 24-72 hours in 3 rabbits: Erythema 3.0, 3.0, 3.0; edema 2.67, 3.33, 4.0, not fully reversible after 7 days. The post-observation time was only 7days and was not long enough to confirm supposed reversibility.

Under the conditions of this skin irritation study in rabbits the test substance at concentration of 100% was irritating to the skin. Concentrations of 1, 5 and 25% of the test substance were considered not irritating to skin.