Registration Dossier

Administrative data

Description of key information

Two key studies: one for in-vivo eye irritation in rabbit and one for skin irritation in rabbitt.  Both studies were not irritating.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
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
Qualifier:
according to
Guideline:
other: Method B4, Commission Directive 92/69/EEC
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals 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
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.
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.
Interpretation of results:
not irritating
Remarks:
Migrated information 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.


Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation
Remarks:
in vitro
Type of information:
experimental study
Adequacy of study:
key study
Study period:
7th- 16th of August 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study completed according to GLP.
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Principles of method if other than guideline:
Three rabbits were each administered a single ocular dose of 50 mg of the test substance and observed for seven days after instillation
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Source:Interfauna (U.K.) Ltd., Huntingdon, Cambridgeshire, England.
Age:11 to 13 weeks of age
Wright:range of 2.5 to 3.2 kg
Housing:housed individually in metal cages with perforated floors in Building R 14 Room 5.
Diet:A standard laboratory diet SOS Stanrab (P) Rabbit Diet and drinking water were provided ad libitum
Temp:approximately 19°C
Humidity:relative humidity at 30 - 70%.
Acclimation:All rabbits were acclimatised to the experimental environment
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
Air Changes: Air exchange was maintained at approximately 19 air changes per hour
Vehicle:
unchanged (no vehicle)
Controls:
other: The contralateral eye of each rabbit remained untreated.
Amount / concentration applied:
Approximately 50 mg of the test substance, the weight occupying a volume of 0.1 ml, was placed into the lower everted lid of one eye of each animal.
Duration of treatment / exposure:
One animal was treated in advance of the others, to ensure that if a severe response was produced, no further animals would be exposed. The eyelids were then gently held together for one second before releasing.
Observation period (in vivo):
Examination of the eyes was made after 1 hour and 1, 2, 3 (equivalent to 24, 48 and 72 hours after instillation), 4 and 7 days after instillation. Observation of the eyes was aided by the use of a handheld light
Number of animals or in vitro replicates:
3
Details on study design:
The study was designed to assess eye irritation potential of UK-143, 108 following a single instillation into the eye of the rabbit. The test substance may come into contact with the eye during handling or use.

The study was conducted in compliance with the following guidelines:

EEC Methods for the determination of toxicity, Annex to Directive 92/69/EEC (OJ No. L383A, 29.12.92), Part B, Method B.5. Acute toxicity (eye irritation).

The albino rabbit was chosen as it has been shown to be a suitable model for eye irritation studies and is the animal recommended in the test guideline.

The amount of test substance instilled was chosen in compliance with the guideline.

The protocol was approved by the Study Director on 27 July 1995, by HRC Management on 30 June 1995 and by the Sponsor on 17 July 1995.
Irritation parameter:
overall irritation score
Remarks:
in vitro score
Basis:
mean
Time point:
other: 4 hours
Score:
0
Irritant / corrosive response data:
All rabbits scored 0 for every region of the eye
Other effects:
CLINICAL SIGNS
There were no signs of toxicity or ill health in any rabbit during the observation period

OCULAR RESPONSES

No corneal damage or iridial inflammation was observed.

Temporary mild conjunctival reactions only were seen.

The eyes were normal one day after instillation.

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
A single instillation of UK-143,108 into the eye of the rabbit elicited transient mild conjunctival irritation only. All reactions had resolved one day after instillation.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Two key studies following OECD and under GLP conditions: one for in-vivo eye irritation in rabbit and one for skin irritation in rabbit. Both studies were not irritating and therefore substance is not classified for these endpoints.