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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:
25th July - 7th August 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report date:
1995

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Reference substance name:
New Eporva 800
IUPAC Name:
New Eporva 800
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): New Eporva 800
- Physical state: Orange coloured liquid
- Analytical purity: 40%
- Batch No.: 504008
- Expiration date of the lot/batch: 31 October 1995
- Storage condition of test material: Room temperature in the dark
- Other:
- Date received: 14 June 1995

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River UK Ltd, Margate, Kent, England.
- Age at study initiation: Approximately 15 weeks of age (prior to treatment (Day 1)).
- Weight at study initiation: 3.3 to 3.6 kg.
- Housing: Individually in plastic cages with perforated floors.
- Diet (e.g. ad libitum): SDS Stanrab (P) Rabbit Diet ad libitum
- Water (e.g. ad libitum): Drinking water ad libitum
- Acclimation period: All rabbit were acclimatised to the experimental environment.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 (approximately)
- Humidity (%): 30 - 70 (relative humidity)
- Air changes (per hr): 19 (approximately)
- Photoperiod (hrs dark / hrs light): 12 hours of artificial light (0700 - 1900 hours) in each 24 hours period.

IN-LIFE DATES: From: 25 July 1995 To: 7 August 1995.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
4 hours
Observation period:
- Environmental parameters: Recorded daily.
- Clinical signs: All animals were observed daily for signs of ill health or toxicity.
- Dermal responses: Examination of the treated skin was made on Day 1 (i.e. approximately 60 minutes after removal of the dressings) and on Days 2, 3 and 4 (equivalent to 24, 48 and 72 hours after exposure). Additional observations were made on Days 5 to 14.
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: Approximately 24 hours prior to application of the test substance, hair was removed with electric clippers from the dorso-lumbar region of each rabbit exposing an area of skin approximately 100 mm x 100 mm. A 0.5 ml amount of the test substance was applied under a 25 mm x 25 mm gauze pad to one intact skin site on each animal.

- Type of wrap if used: Each treatment site was covered with “Elastoplast” elastic adhesive dressing for four hours.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the exposure period, the semi-occlusive dressing and gauze pad were removed and the treatment site was washed with warm water (30° to 40°C) to remove any residual test substance. The treated area was blotted dry with absorbent paper.
- Time after start of exposure: 4 hours

SCORING SYSTEM: Local dermal irritation was assessed using the prescribed numerical system in the attached report. Any other lesion not covered by this scoring system, was described.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3.3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Necrosis.
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3.3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Necrosis.
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3.3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Necrosis.
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Edges of necrotic area lifting.
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.3
Max. score:
2
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Edges of necrotic area lifting.
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.3
Max. score:
2
Reversibility:
not fully reversible within: 14 days.
Remarks on result:
other: Edges of necrotic area lifting.
Irritant / corrosive response data:
- Dermal responses: The numerical values given to the dermal reactions elicited by New Eporva 800 are shown in Table 1 of the attached report. Well-defined dermal reactions were seen following removal of bandages. Severe dermal irritation with necrosis developed in all these animals on Day 2 and persisted throughout the observation period to Day 14 (day of termination).
Other effects:
- Clinical signs: There were no signs of toxicity or ill health in any rabbit during the observation period.

Any other information on results incl. tables

Table 1. Dermal reactions observed after application of New Eporva 800

Rabbit number and sex
E = Erythema
O = Oedema
Day
1*
2
3
4
5
6
7
8
9
10
11
12
13
14
1250
E
a2
b4
b4
b4
b4
b4
b4
b4
b4
b4
b4
b4
b4
b4
O
2
2
2
1
1
1
1
c1
c1

c1

c1

c1

c1

c1

1251
E
a2
b4
b4
b4
b4
b4
b4
b4
b4
b4
b4
b4
b4
b4
O
2
1
1
1
1
1
1
c1
c1

c1

c1

c1

c1

c1

1259
E
a2
b4
b4
b4
b4
b4
b4
b4
b4
b4
b4
b4
b4
b4
O
2
1
1
1
1
1
1
1
c1

c1

c1

c1

c1

c1

 
* Approximately 60 minutes after removal of the dressing
a Brown staining from dose; b Necrosis; c Edges of necrotic area lifting

Applicant's summary and conclusion

Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Conclusions:
A single semi-occlusive application of New Eporva 800 to intact rabbit skin for four hours elicited severe persistent dermal irritation. The necrosis, severe erythema and the persistence until day 14 of the study after a 4 hour exposure period warrant a classification as category 1B (H314 causes severe burns and eye damage).

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