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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:
1st - 4th of August 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: done under GLP and OECD method

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report date:
1997

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: Method B4, Commission Directive 92/69/EEC
GLP compliance:
yes

Test material

Constituent 1
Test material form:
solid: crystalline
Details on test material:
Intended use: Pharmaceutical intermediate
Expiry: 19 November 1995
Purity: 99.6% excluding organic solvents
Appearance: White to off-white crystalline solid
Storage conditions: Room temperature
Date received: 19 May 1995

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source:Froxfield (U.K.) Ltd., Petersfield, Hampshire, England.
- Age at study initiation:13 to 15 weeks of age
- Weight at study initiation:weight range of 3.0 to 3.8 kg
- Housing:They were housed individually in plastic cages with perforated floors in Building R 14 Room 1.
- Diet (e.g. ad libitum):A standard laboratory diet SDS Stanrab (P) Rabbit Diet
- Water (e.g. ad libitum):drinking water were provided ad libitum
- Acclimation period: All rabbits were acclimatized to the experimental environment

ENVIRONMENTAL CONDITIONS
- Temperature (°C):approximately 19°C
- Humidity (%):relative humidity at 30 - 70%.
- Air changes (per hr):approximately 19 air changes per hour
- Photoperiod (hrs dark / hrs light):lighting was controlled by means of a time switch to give 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:
unchanged (no vehicle)
Controls:
other: contralateral zone of same animal
Amount / concentration applied:
0.5g
Duration of treatment / exposure:
4hr
Observation period:
All animals were observed daily for signs of ill health or toxicity. 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:
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 g amount of the test substance was applied under a 25 mm x 25 mm gauze pad which had been moistened with 0.5 ml distilled water to one intact skin site on each animal.

Each treatment site was covered with "Elastoplast" elastic adhesive dressing for four hours. The animals were not restrained during the exposure period and were returned to their cages immediately after treatment.

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.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
(mean score 2)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
(mean score 3)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
(mean score 2)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
(mean score 3)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Other effects:
CLINICAL SIGNS
There were no signs of toxicity or ill health in any rabbit during the observation period.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
A single semi-occlusive application of UK-143, 108 to intact rabbit skin for four hours elicited no dermal irritation.