Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
09 April - 17 April, 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study was conducted according to OECD and in accordance with GLP. The study material is well characterized

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
92/69/EEC
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
424-660-8
EC Name:
-
Cas Number:
224631-15-6
Molecular formula:
Hill formula: C18H26N4O5S CAS formula: C18H26N4O5S
IUPAC Name:
(S)-2,5-dioxopyrrolidin-1-yl 2-(3-((2-isopropylthiazol-4-yl)methyl)-3-methylureido)-3-methylbutanoate

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Eight female rabbits from HRP Inc, Kalamazoo, Michigan weighing 2- 2.5 kg (approx. 13 weeks) on arrival were allowed to acclimatise for 7 days before treatment. 6 animals were assigned to the study.
The animals were housed in individual stainless steel ventilated hanging cages. 100 -130g Certified High Fibre Rabbit Chow was provided each day and water ad libitum. The temperature was maintained at 63 - 68°F. The animal room was on a 12 hour daily light cycle.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: other: right eye of each animal was untreated
Amount / concentration applied:
0.1ml
Duration of treatment / exposure:
0.1gl test material was placed in the conjunctival sac of the left eye after gently pulling the lower eye lid away from the eyeball. The upper and lower eyelid were held closed for about one or two second after treatment to prevent loose of material and then released. The right eye was left untreated to serve as the control.
Observation period (in vivo):
After the 24hr observation period the eyes of all rabbits were washed with lukewarm water.
All animals were observed daily for signs of ill health or toxicity.
Evaluations made at 1, 24, 48, 72 hrs and days 4 and 7 after treatments.
Number of animals or in vitro replicates:
6 female rabbits
Details on study design:
On the day prior to treatment the eyes were checked by a veterinarian.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
conjunctivae score
Basis:
mean
Score:
ca. 2
Max. score:
3
Remarks on result:
other: max duration 7 h; max value at end of observation period: 3
Irritation parameter:
chemosis score
Basis:
mean
Score:
ca. 2.5
Max. score:
4
Remarks on result:
other: max duration 7 h; max value at end of observation period: 3
Irritation parameter:
iris score
Basis:
mean
Score:
ca. 1
Max. score:
3
Remarks on result:
other: max duration 7 h; max value at end of observation period: 2
Irritation parameter:
iris score
Basis:
mean
Score:
ca. 0.5
Max. score:
1
Remarks on result:
other: max duration 7 h; max value at end of observation period: 1
Other effects:
Local irritation observed in the treated eye of all 6 rabbits included: corneal opacity (grades 1,2 or 3) , conjunctivial redness (grades 2 or 3), conjunctival chemosis (grades 3 or 4) and conjuctival discharge (grades 1, 2 or 3).

Iritis (grade 1) was noted in the eye of 5 rabbits.

Little or no improvement in the corneal or conjuctival irritation was noted in the treated eye of rabbits through day 7 of the observation period.

Any other information on results incl. tables

No overt signs of toxicity were observed in rabbits following test material application to the anterior surface of the eye in this study.

Applicant's summary and conclusion

Interpretation of results:
other: Severe local irritation
Conclusions:
Abbott-133816.0 produced severe local irritation in the eye of all rabbits following a single application to the anterior surface of the eye in this study.
Executive summary:

Abbott-133816.0 produced severe local irritation in the eye of all rabbits following a single application to the anterior surface of the eye in this study.

Little or no improvement in the corneal or conjuctival irritation was noted in the treated eye of rabbits through day 7 of the observation period.