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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:
From January 13 to February 05, 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
Adopted 24th April 2002
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
UK GLP Compliance Programme (inspected on August 19, 2008/ signed on March 04, 2009)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Remarks:
paste / solid block
Details on test material:
- Physical state: solid, pale yellow to yellow block, or pasty
- Stability under test conditions: no data
- Storage condition of test material: in the dark, preferably at about 4-10°C and under nitrogen.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Limited, Bicester, Oxon, UK.
- Age at study initiation: 12-20 weeks
- Weight at study initiation: 2-3.5 kg
- Housing: Animals were housed individually in suspended cages.
- Diet: Food (2030 Teklad Global Rabbit diet supplied by Harlan Teklad, Bicester, Oxon, UK), ad libitum
- Water: Mains drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17-23 °C
- Humidity: 30-70 %
- Air changes: 15 changes/h
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: From: January 13, 2009 To: February 05, 2009

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
other: test material was moistened with distilled water
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
- Test material was ground to a fine powder prior to application.
- 0.5 g of the test material was moistened with 0.5 mL of distilled water before applied on to the skin.
Duration of treatment / exposure:
First animal: 3 minutes, 1 and 4 h
Second and third animal: 4 h
Observation period:
1, 24, 48 and 72 h and 7 and 14 days after the removal of the patch
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: Dorsal/flank area
- Type of wrap if used: Test material moistened with distilled water 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.
- To prevent the animal interfering with the patches, the trunk of the rabbit was wrapped in an elasticated corset for the duration of the exposure period.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): One patch was removed at each of three time points: 3 minutes, 1 and 4 h after application of test material. Any residual test material was removed by gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: 3 minutes, 1 and 4 h

SCORING SYSTEM: Draize scale, as described in OECD Guideline No. 404

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: mean 24, 48 and 72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: mean 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: mean 24, 48 and 72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: mean 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: mean 24, 48 and 72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: mean 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
- Following 3 minutes exposure period, no evidence of skin irritation was observed.
- Following 1 h exposure period, very slight erythema was observed at the treated skin site at the 24, 48 and 72 h. The treated skin site appeared normal at the 7-day observation.
- Following 4 h exposure period, well-defined erythema was noted at two treated skin sites with very slight erythema noted at the remaining treated skin site at the 24, 48 and 72 h. Very slight oedema was noted at two treated skin sites at the 24, 48 and 72 h. Loss of skin flexibility and/or elasticity was noted at two treated skin sites and light brown discolouration of the epidermis was noted at one treated skin site at the 48 and 72 h. Slight desquamation was noted at all treated skin sites on Day 7. Two treated skin sites were fully reversible on Day 14.
Other effects:
- Animals showed expected gain in bodyweight during the 14 day study.

Any other information on results incl. tables

Table 7.3.1/1: Mean irritant/corrosive response data for each animal at each observation time

Score at time point

Erythema (Animal no 1 / 2 / 3)

Max. score 4

Oedema (Animal no 1 / 2 / 3)

Max. score 4

1 h

0 / 0 / 0

0 / 0/ 0

24 h

2 / 1 / 2

1/ 0 / 1

48 h

2 / 1 Le / 2 Le Br

1/ 0 / 1

72 h

2 / 1 Le / 2 Le Lf Br

1/ 0 / 1

7 days

0 D / 0 D / 0 D

0 / 0 / 0

14 days

* / 0 / 0

* / 0 / 0

Average 24h, 48h, 72h

2 / 1 / 2

1 / 0 / 1

Le = loss of skin elasticity; Lf = loss of skin flexibility; Br = light brown discolouration of the epidermis; D = slight desquamation; * = observation not required

Applicant's summary and conclusion

Interpretation of results:
Category 3 (mild irritant) based on GHS criteria
Conclusions:
Under the test conditions :
- no additional self-classification is proposed for the registered substance regarding skin irritation according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP)
- the registered substance is classified as Category 3 according to the GHS based on the individual scores for each animal within 3 scoring times (24, 48 and 72 h) for erythema (2.0 / 1.0 / 2.0).

Executive summary:

In a dermal irritation study performed according to the OECD Guideline No. 404, and in compliance with GLP, 0.5 g of test material moistened with distilled water was applied on the clipped skin of the dorsal flank area of 3 male New Zealand White rabbits. Test sites were covered with a semi-occlusive dressing for 4 h. Skin irritation was assessed and scored according to the Draize scale at 1, 24, 48, 72 h and 7 and 14 days after the removal of the patch. First animal was exposed for 3 minutes, 1 and 4 h showed no corrosive effects.

No evidence of skin irritation was observed following 3 minutes exposure period. Very slight erythema was observed at the treated skin site at the 24, 48 and 72 h and found fully reversible on Day 7 after 1 h exposure. After 4 h exposure period, well-defined erythema was noted at two treated skin sites with very slight erythema noted at the remaining treated skin site at the 24, 48 and 72 h. Very slight oedema was noted at two treated skin sites at 24, 48 and 72 h. Loss of skin flexibility and elasticity was noted at two treated skin sites and light brown discolouration of the epidermis was noted at one treated skin site at 48 and 72 h. Slight desquamation was noted at all treated skin sites on Day 7. Two treated skin sites were fully reversible on Day 14.

The individual scores for each animal within 3 scoring times (24, 48 and 72 h) were 2.0 / 1.0 / 2.0 for erythema and 1.0 / 0.0 / 1.0 for oedema.

Based on the available data :

- no additional self-classification is proposed for the registered substance regarding skin irritation according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP)

- the registered substance is classified as Category 3 according to the GHS based on the individual scores for each animal within 3 scoring times (24, 48 and 72 h) for erythema (2.0 / 1.0 / 2.0).

This study is considered as acceptable and satisfies the requirement for skin irritation endpoint.