(S)-3-methyl-2-(2-oxotetrahydropyrimidine-1-yl)butyric acid

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17 September 1997 - 06 February 1998

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

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

Test material information

Constituent 1

Reference substance name:

-

EC Number:

430-900-2

EC Name:

-

Cas Number:

192725-50-1

Molecular formula:

Hill formula: C9H16N2O3 CAS formula: C9H16N2O3

IUPAC Name:

3-methyl-2-(2-oxo-1,3-diazinan-1-yl)butanoic acid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Six male rabbits from Covance Research Products Inc, Kalamazoo, Michigan weighing 2- 2.5 kg (approx. 14 weeks old) on arrival were allowed to acclimatise for 14 days before treatment. 5 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 67 - 70°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:

53mg (which, when gently compacted, occupied approx.0.1ml)

Duration of treatment / exposure:

53mg test material was instilled into the lower everted lid of the left eye. The material was placed in the conjuctival 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 forsurvival and general body condition.
Evaluations made at 1, 24, 48, 72 hrs and days 4, 7, 14 and 21 after treatments.

Number of animals or in vitro replicates:

5 male rabbits

Details on study design:

Prior to treatment the eyes were checked by a veterinarian.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: na

Score:

ca. 1

Max. score:

1

Reversibility:

fully reversible within: 72 hours

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: max irritation observed

Score:

> 1 - <= 2

Max. score:

2

Reversibility:

fully reversible within: 72 hrs

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: na

Score:

>= 2 - <= 3

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: na

Score:

>= 2 - <= 4

Max. score:

4

Reversibility:

fully reversible within: 72 hrs

Results 5

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: na

Score:

>= 1 - <= 2

Max. score:

2

Reversibility:

fully reversible within: 72 hrs

Results 6

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: na

Score:

>= 1 - <= 2

Max. score:

2

Reversibility:

fully reversible within: 7 days

Results 7

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

21 d

Score:

ca. 1

Max. score:

1

Reversibility:

not specified

Results 8

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

21 d

Score:

ca. 1

Max. score:

1

Reversibility:

not specified

Results 9

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

21 d

Score:

ca. 1

Max. score:

1

Reversibility:

not specified

Results 10

Irritation parameter:

cornea opacity score

Basis:

animal #5

Time point:

21 d

Score:

ca. 1

Max. score:

1

Reversibility:

not specified

Results 11

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

21 d

Score:

ca. 1

Max. score:

1

Reversibility:

not specified

Irritant / corrosive response data:

The maximum irritation grades observed in the treated eye of rabbits in this study were: corneal opacity (grades 1 or 2), involving at least ¾ of the cornea was observed in the treated eye of 3 rabbits; iritis (grade 1), in 1 of the above 3 rabbits; conjunctival redness (grades 2 or 3), conjunctival chemosis (grades 2, 3 or 4) and conjuctival discharge (grades 2 or 3).
Signs of irritation were completely reversible by 72 hrs after initial instillation in two rabbits and by day 7 in a third rabbit.
Corneal opacity (grade 1), conjunctival chemosis (grade 1) and conjunctival discharge (grade 1) were observed in the eye of the remaining 2 rabbits on day 21. In addition, grade 1 conjunctival redness wase noted in one of the same two rabbits on day 21.

Any other information on results incl. tables

Body weights ranged from 2.2 to 2.6kg on the day of treatment. No apparent treatment-related body weight changes were observed during the observation period following treatment.

Applicant's summary and conclusion

Interpretation of results:

irritating

Remarks:

Migrated information

Conclusions:

Abbott-164220 produced irritation in the treated eye of rabbits in this study.

Executive summary:

Abbott-164220 produced irritation in the eye of rabbits in this study.