Registration Dossier

Administrative data

Description of key information

Skin irritation/corrosion (OECD 404): corrosive

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:
14 - 21 Oct 2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted in Apr 2002
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
(2004/73/EC)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
THE DEPARTMENT OF HEALTH OF THE GOVERNMENT OF THE UNITED KINGDOM, UK
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Limited, Bicester, UK
- Age at study initiation: 12 - 20 months
- Weight at study initiation: 2.0 - 3.5 kg
- Housing: individually in suspended cages, environmental enrichment items were provided
- Diet: 2030 Teklad Global Rabbit diet (Harlan Teklad, Bicester, UK), ad libitum
- Water: mains drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23
- Humidity (%): 30 - 70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: Untreated sites of the same animal served as control.
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 g test material moistened with 0.5 mL distilled water
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 males
Details on study design:
TEST SITE
- Area of exposure: on the back
- Type of wrap: The test substance was introduced under a 2.5 cm x 2.5 cm cotton gauze patch and placed in position on the shorn skin. The patch was secured in position with a strip of surgical adhesive tape.

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize scoring system
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: mean after 24/48/72 h
Score:
3.3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3.3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3.3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritant / corrosive response data:
Green coloured dermal necrosis (attributed a Draize score of 4 for injuries in depth) was noted at all treated skin sites 1 and 24 h after patch removal with moderate to severe erythema noted at 48 and 72 h after patch removal.
Slight oedema was noted at all treated skin sites 1, 24, 48 and 72 h after patch removal.
Dermal haemorrhage covering the majority of the test site was noted in all animals 48 and 72 h after patch removal. A black scab, approximately 3 mm x 3 mm in size, located on the lower right hand corner of the test site was noted in one animal at the 48 and 72-h observations and in two animals at the 7-day observation. A black scab, undulating in appearance, located on the lower and right hand edges of the test site was noted in one animal at the 48 and 72-h observations with a sunken, hardened, dark brown/black coloured scab, resembling a crater, noted at the 7-day observation. Adverse skin reactions prevented accurate evaluation of erythema and oedema at all treated skin sites 7 days after patch removal.
The skin reactions were considered to be irreversible and indicative of full thickness tissue destruction. Therefore, the animals were sacrificed for humane reasons immediately after the 7-day observation.

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

4 N

2

4 N

2

4 N

2

24 h

4 N

2

4 N

2

4 N

2

48 h

3 Hd, St

2

3 Hd, St*

2

3 Hd

2

72 h

3 Hd, St

2

3 Hd, St*

2

3 Hd

2

7 days

?e, St, Sw, K

?od

?e, Su, K

?od

?e, St, Sw, K

?od

Mean value
24 + 48 + 72 h

3.3

2.0

3.3

2.0

3.3

2.0

N: green coloured dermal necrosis

Hd: dermal haemorrhage covering the majority of the test site

St: black scab, approximitaly 3 mm x 3mm in size, located on the lower right hand corner of test site

St*: black scab, undulating in appearance, located on the lower and right hand edge of test site

Sw: scab undulating

Su: sunken, hardened, dark brown/black coloured scab resembling a crater

?e: adverse reactions prevented evaluation of erythema

?od: adverse reactions prevented evaluation of oedema

K: killed for humane reasons

All animals showed expected body weight gain during the study.

Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Conclusions:
Under the conditions of this skin irritation study in rabbits the test substance is corrosive to the skin. Considering the severe effects (erythrema score 4 and necrosis at 1-h reading time point) worst case approach was considered and the test substance was classified as Skin Corr. 1B (H314).
Executive summary:

The study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method was designed to meet the requirements of the following: OECD Guidelines for the Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion" (adopted 24 April 2002) and Method B4 Acute Toxicity (Skin Irritation) of Corxunission Directive 2004/73/EC. A single 4-hour, semi-occluded application of the test material to the intact skin of three

rabbits produced reactions indicative of dermal corrosion. The reactions included severe erythema and scabbing. The skin reactions were considered to be irreversible and indicative of full thickness tissue destruction, therefore, the animals were killed for humane reasons immediately after the 7-day observation, in accordance with Company policy and current UK Home Office guidelines.

In conclusion, the test material was classified as corrosive to rabbit skin.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a skin irritation/corrosion study according to OECD Guideline 404 and in compliance with GLP, 0.5 g of the test substance moistened with 0.5 mL of distilled water was applied to the clipped skin of 3 New Zealand White rabbits under semi-occlusive conditions for 4 h (2008). Scoring of skin reactions (erythema and edema) was performed 1, 24, 48 and 72 h and 7 days after patch removal. Exposure to the test substance resulted in severe erythema (grade 4) and necrosis in all animals 1 and 24h after patch removal and moderate to severe erythema (grade 3) in all animals 48 and 72 h after patch removal. Slight oedema was noted at all treated skin sites 1, 24, 48 and 72 h after patch removal. The irritation score over 24, 48 and 72 h was 3.3 for erythema and 2.0 for edema for each animal, respectively. Adverse skin reactions (dermal haemorrhage and black scab) prevented accurate evaluation of erythema and oedema at all treated skin sites 7 days after patch removal. The skin reactions were considered to be irreversible and indicative of full thickness tissue destruction. Therefore, the animals were sacrificed for humane reasons immediately after the 7-day observation. Based on the results, the test substance was corrosive to the skin under the conditions of the test.

Justification for classification or non-classification

The available data on skin irritation meet the criteria for classification as Skin Corr. 1B (H314) according to Regulation (EC) 1272/2008 and thus the substance is additionally classified as Eye damage 1.