Registration Dossier

Toxicological information

Eye irritation

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Administrative data

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.

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.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

Test material

Constituent 1
Chemical structure
Reference substance name:
2-ethoxy-5-(4-methyl-1-piperazinylsulfonyl)benzoic acid
EC Number:
424-110-7
EC Name:
2-ethoxy-5-(4-methyl-1-piperazinylsulfonyl)benzoic acid
Cas Number:
194602-23-8
Molecular formula:
C14 H20 N2 O5 S
IUPAC Name:
2-Ethoxy-5-(4-methyl-1- piperazinylsulphonyl)-benzoic acid
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 / tissue source

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

Test system

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.

Results and discussion

In vivo

Results
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

Any other information on results incl. tables

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.

Applicant's summary and conclusion

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.