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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:
25 September to 09 October 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP study conducted in compliance with OECD Guideline No. 404 without any deviation.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted 24 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 July 10, 2012/ signed on November 30, 2012)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Physical state: Pale yellow liquid
- Storage condition of test material: Approximately 4 °C in the dark under nitrogen

Test animals

Species:
rabbit
Strain:
New Zealand White
Remarks:
Hsdlf:NZW
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Leicestershire, UK.
- Age at study initiation: 12-20 weeks
- Weight at study initiation: 2.20-2.65 kg
- Housing: Animals were individually housed in suspended cages.
- Diet: Food (2930C Teklad Global Certified Rabbit diet supplied by Harlan Laboratories UK Ltd., 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: 25 September to 09 October 2012

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration: For the purpose of the study the test item was used as supplied.
Duration of treatment / exposure:
4 h
Observation period:
1, 24, 48 & 72 h and 7 and 14 days after the removal of the patch
Number of animals:
3 males
Details on study design:
PRETRAEATMENT
- On the day before the test each of a group of three rabbits was clipped free of fur from the dorsal/flank area using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study.

TEST SITE
- Area of exposure: On the day of the test a suitable test site was selected on the back of each rabbit.
- Type of wrap if used: A quantity of 0.5 mL of the test item was applied directly to the skin under a 2.5 cm x 2.5 cm cotton gauze patch. The patch was secured in position with a strip of surgical adhesive tape. To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset and the animals were returned to their cages for the duration of the exposure period.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Four hours after application the corset and patches were removed from each animal and any residual test item removed by gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
- Immediately following removal of the patches and approximately 1, 24, 48 & 72 h and 7 and 14 days after the removal of the patch

SCORING SYSTEM:
- Method of calculation: Test sites were examined for evidence of primary irritation and scored according to the Draize scale, as described in OECD Guideline No. 404

OTHERS:
- Individual bodyweights were recorded on Day 0 (the day of dosing) and at the end of the observation period.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Remarks:
due to the persistence of the reaction
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
probability of mild irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
probability of mild irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
probability of mild irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Remarks:
due to the persistence of the reaction
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
probability of mild irritation
Irritant / corrosive response data:
- Very slight erythema and very slight or slight oedema was noted at all treated skin sites immediately after patch removal. Very slight erythema with or without very slight oedema was noted at all treated skin sites one hour after patch removal. Well-defined erythema and very slight or slight oedema was noted at all treated skin sites at the 24 hour observation with well-defined erythema and slight oedema noted at the 48 and 72 hour observations. Very slight erythema and very slight oedema was noted at one treated skin site at the 7-Day observation.
- Loss of skin elasticity was noted at all treated skin sites at the 48 and 72 hour observations. Moderate desquamation was noted at all treated skin sites at the 7-Day observation. Small superficial scattered scabs and hardened light brown coloured scab were noted at two treated skin sites at the 7-Day observation. Scab lifting to reveal glossy skin was also noted at one treated skin site at the 7-Day observation. Adverse reactions prevented evaluation of erythema at one treated skin site at the 7-Day observation. Glossy skin was noted at two treated skin sites at the 14-Day observation.
- One treated skin site appeared normal at the 14-Day observation.
Other effects:
All animals showed expected gain in bodyweight during the 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

Immediately

1 / 1 / 1

2 / 1 / 2

1 h

1 / 1 / 1

1 / 0/ 1

24 h

2 / 2 / 2

2 / 1 / 2

48 h

2 Le / 2 Le / 2 Le

2 / 2 / 2

72 h

2 Le / 2 Le / 2 Le

2 / 2 / 2

7 days

1SsSpD / 0 D /?eSsSpSgD

1 / 0 / 0

14 days

0G / 0 /0G

0 / 0 / 0

Mean 24, 48 and 72 h

2.0 / 2.0 / 2.0

2.0 / 1.7 / 2.0

Le = Loss of skin elasticity

Ss = Small superficial scattered scabs

Sp = Hardened light brown coloured scab

Sg = Scab lifting to reveal glossy skin

D = Moderate desquamation

G = Glossy skin

?e = Adverse reactions prevent evaluation of erythema

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
Under the experimental conditions of this study, the test item is classified as irritant (Category 2) according to Regulation (EC) No 1272/2008 (CLP) and to GHS based on the persistence of inflammation until the end of the 14 -day observation period in 2 out of 3 animals.
Executive summary:

In a dermal irritation study performed according to the OECD Guideline No. 404, and in compliance with GLP, 0.5 mL of test item was applied on the clipped skin of the dorsal/flank area (back) 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.

Very slight erythema and very slight or slight oedema was noted at all treated skin sites immediately after patch removal. Very slight erythema with or without very slight oedema was noted at all treated skin sites one hour after patch removal. Well-defined erythema and very slight or slight oedema was noted at all treated skin sites at the 24 hour observation with well-defined erythema and slight oedema noted at the 48 and 72 hour observations. Very slight erythema and very slight oedema was noted at one treated skin site at the 7-Day observation. Loss of skin elasticity was noted at all treated skin sites at the 48 and 72 hour observations. Moderate desquamation was noted at all treated skin sites at the 7-Day observation. Small superficial scattered scabs and hardened light brown coloured scab were noted at two treated skin sites at the 7-Day observation. Scab lifting to reveal glossy skin was also noted at one treated skin site at the 7-Day observation. Adverse reactions prevented evaluation of erythema at one treated skin site at the 7-Day observation. Glossy skin was noted at two treated skin sites at the 14-Day observation. One treated skin site appeared normal at the 14-Day observation.

The individual scores for each animal within 3 scoring times (24, 48 and 72 h) were 2.0 / 2.0 / 2.0 for erythema and 2.0 / 1.7 / 2.0 for oedema.

Under the experimental conditions of this study, the test item is classified as irritant (Category 2) according to Regulation (EC) No 1272/2008 (CLP) and to GHS based on the persistence of inflammation until the end of the 14 -day observation period in 2 out of 3 animals.

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