1H-Pyrazole-5-carboxamide, 4-[[2-ethoxy-5-[(4-methyl-1-piperazinyl)sulfonyl]benzoyl]amino]-1-methyl-3-propyl-

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

6th to 9th August 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

The upper value for humidity recorded was 73%. This deviation is not considered to have affected the integrity or validity of the study.

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

1

Reference substance name:

4-[2-Ethoxy-5-(4-methyl-1-piperazinylsulfonyl)benzamido]-1-3-propyl-1H-pyrazole-5-carboxamide

EC Number:

639-263-7

Cas Number:

200575-15-1

Molecular formula:

C22H32N6O5S

IUPAC Name:

4-[2-Ethoxy-5-(4-methyl-1-piperazinylsulfonyl)benzamido]-1-3-propyl-1H-pyrazole-5-carboxamide

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- batch No.of test material: 92480/N/9/1
- Expiration date of the lot/batch: Not supplied
- Purity: 95 %

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK
- Age at study initiation: 12 to 13 weeks
- Weight at study initiation: 2.8 to 3.1 kg
- Housing: housed individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: period not specified (prior to treatment (Day 1). All rabbits were acclimatised to the experimental environment.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15.5 to 25°C
- Humidity (%): 51 - 73%
- Air changes (per hr): 19
- Photoperiod (hrs dark / hrs light): 12 hours of artificial light (0700 - 1900 hours) in each 24 hours period.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

not specified

Amount / concentration applied:

Approximately 0.5g of the test substance was applied under a 25 mm x 25 mm gauze pad which was then moistened with 0.5 ml distilled water, to one intact skin site on each animal.

Duration of treatment / exposure:

72 hours

Observation period:

Examination of the treated skin was made on Day 1 (ie approximately 60 minutes after removal of the dressings) and on Days 2, 3 and 4 (equivalent to 24, 48 and 72 hours after exposure).

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: dorso-lumbar region of each rabbit exposing an area of skin approximately 100 mm x 100 mm.
- Type of wrap if used: 25 mm x 25 mm gauze pad

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) and the test area was blotted dry with absorbent paper.
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
Clinical signs: daily
Dermal responses: Day 1 (approximately 60 mins after removal of the dressings) and on Days 2, 3 and 4.

SCORING SYSTEM:
- Method of calculation: Local dermal irritation was assessed using the prescribed numerical system:

Erythema and eschar formation:
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth) preventing erythema reading 4

Oedema formation:
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by definite raising) 2
Moderate oedema (raised approximately 1 millimetre) 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure) 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

A single semi-occlusive application of UK-220,955 to intact rabbit skin for four hours elicited no dermal irritation.

Executive summary:

A study was performed to assess the skin irritation potential of UK-220,955 to the rabbit. The method followed was that described in EEC Methods for the determination of toxicity, Annex to Directive 92/69/EEC (OJ No. L383A, 29.12.92), Part B, Method B.4. Acute toxicity (skin irritation).

Three rabbits were each administered a single dermal dose of 0.5 g of the test substance and observed for four days.

No dermal reactions were observed in any animal following a single semi-occlusive application of UK-220,955 to intact rabbit skin for four hours.

UK-220,955 will not require labelling in accordance with GHS.