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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:
14 - 21 Oct 2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guidelineopen allclose all
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

Reference
Name:
Unnamed
Type:
Constituent

Test animals

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

Test system

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

Results and discussion

In vivo

Resultsopen allclose all
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.

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

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.

Applicant's summary and conclusion

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.