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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
01 December 2003 and 11 December 2003.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: performed according to OECD and EC test guidelines and GLP compliant

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report Date:
2004

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Sponsor's identification : SB-322069
Description : white solid
Batch number : AS103703-054A1
Date received : 29 October 2003
Storage conditions : room temperature in the dark

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Three New Zealand White rabbits were supplied by David Percival Ltd, Moston, Sandbach,
Cheshire, UK. At the start of the study the animals were in the weight range of 2.0 to 3.5 kg and
were twelve to twenty weeks old. After an acclimatisation period of at least five days each animal
was given a number unique within the study which was written with a black indelible marker-pen
on the inner surface of the ear and on the cage label.
The animals were individually housed in suspended metal cages. Free access to mains drinking
water and food (Certified Rabbit Diet (Code 5322) supplied by International Product Supplies
Limited, Wellingborough, Northants, UK) was allowed throughout the study. The diet and
drinking water were considered not to contain any contaminant of a level that might have affected
the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 17 to 23°C and 30 to 70%
respectively. Any occasional deviations from these targets were considered not to have affected
the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per
hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00
to 18:00) and twelve hours darkness.
The animals were provided with environmental enrichment items which were considered not to
contain any contaminant of a level that might have affected the purpose or integrity of the study.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
A volume of 0.1 ml of the test material, which was found to
weigh approximately 60 mg (as measured by gently compacting the required volume into an
adapted syringe)
Duration of treatment / exposure:
single exposure
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3
Details on study design:
Initially, a single rabbit was treated. A volume of 0.1 ml of the test material, which was found to
weigh approximately 60 mg (as measured by gently compacting the required volume into an
adapted syringe) was placed into the conjunctival sac of the right eye, formed by gently pulling
the lower lid away from the eyeball. The upper and lower eyelids were held together for about
one second immediately after treatment, to prevent loss of the test material, and then released.
The left eye remained untreated and was used for control purposes. Immediately after
administration of the test material, an assessment of the initial pain reaction was made according
to the six point scale shown in Appendix 1.
After consideration of the ocular responses produced in the first treated animal, two additional
animals were treated. In order to minimise pain on application of the test material, one drop of
local anaesthetic (Amethocaine hydrochloride 0.5%, Chauvin Pharmaceuticals, Romford, Essex,
UK) was instilled into both eyes of these animals 1 to 2 minutes before treatment.
Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours
following treatment, according to the numerical evaluation given in Appendix 2, (from Draize J H
(1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity
of Household Substances, National Academy of Sciences, Washington DC p.48 to 49).
Any other ocular effects were also noted. Examination of the eye was facilitated by the use of the
light source from a standard ophthalmoscope.

Results and discussion

In vivo

Results
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
other: 1, 24 , 48 and 72 hours
Score:
7.3
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Irritant / corrosive response data:
No corneal or iridial effects were noted during the study.
Minimal to moderate conjunctival irritation was noted in all treated eyes one hour after patch
removal with minimal conjunctival irritation in one treated eye at the 24 and 48-hour
observations.
Two treated eyes appeared normal at the 24-hour observation and the remaining treated eye
appeared normal at the 72-hour observation.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material produced a maximum group mean score of 7.3 and was classified as a
MILD IRRITANT (CLASS 4 ON A 1 TO 8 SCALE) to the rabbit eye according to a modified
Kay and Calandra classification system.