3-(3-hydroxypropyl)oxazolidin-2-one

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study + GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3-(3-hydroxypropyl)oxazolidin-2-one

EC Number:

431-840-1

EC Name:

3-(3-hydroxypropyl)oxazolidin-2-one

Cas Number:

87010-29-5

Molecular formula:

C6 H11 N O3

IUPAC Name:

3-(3-hydroxypropyl)oxazolidin-2-one

Details on test material:

- Name of test material (as cited in study report): Oxypropazone
- Physical state: light yellowish, viscous liquid
- Analytical purity: 96.5%
- Lot/batch No.: # 120446 / 7.12.90
- Stability under test conditions: According to the sponsor, the test susbtance is stable throughout the experimental period
- Storage condition of test material: The test substance is kept in a container at room temperature

Test animals / tissue source

Species:

rabbit

Strain:

other: Russian White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: ASTA Phama AG
- Age at study initiation: males 7 and 9 month, femal 7 months
- Weight at study initiation: males 2.52 and 2.57 kg, female 2,19 kg
- Housing: Stainless cages with grating floor, one rabbit per cage
- Diet: Approximately 120g/day/animal
- Water: ad libitum
- Acclimation period: Animals were kept one day under test conditions before substance application

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-24
- Humidity (%): 40-70
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): undiluted

Duration of treatment / exposure:

Eyes were not rinsed following substance applicataion

Observation period (in vivo):

At 1, 24, 48 and 72 h; thereafter once daily
Two animals were observed for 3 days, one animal for 6 days

Number of animals or in vitro replicates:

3 animals (two males, one female)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: Eyes were not rinsed following substance application


SCORING SYSTEM: Treated eyes were examined using a Cliptrix pencil light; signs of irritation were assessed qunatitatively and qualitatively using the Draize scale; cornea, iris and conjunctiva were recorded at examination times 1, 24, 48 and 72 h; the irritation index is given by the sum of these scores; in addition, attention was paid ro the occurrence of further reactions on the eye (e.g. corrosive effects) and to clinical symptoms
A corresponding gradation was allocated to the index using the method by Gilman et al:
Index Range Gradation
0-10 non irritatant
11-25 slightly irritant
26-56 moderately irritating
57-110 severely irritating

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

mean

Time point:

other: 24, 48 and 72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible

Results 2

Irritation parameter:

conjunctivae score

Basis:

animal #2

Remarks:

mean

Time point:

other: 24, 48 and 72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #3

Remarks:

mean

Time point:

other: 24, 48 and 72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

mean

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Results 5

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

mean

Time point:

other: 24, 48 and 72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible

Results 6

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

mean

Time point:

other: 24, 48 and 72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible

Results 7

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

mean

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Results 8

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

mean

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible

Results 9

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

mean

Time point:

other: 24, 48 and 72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible

Results 10

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

mean

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible

Results 11

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

mean

Time point:

other: 24, 48 and 72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible

Results 12

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

mean

Time point:

other: 24, 48 and 72 h

Score:

0.66

Max. score:

2

Reversibility:

fully reversible

Irritant / corrosive response data:

The cornea of the third animal showed diffuse areas of opacity over less-than half of the area (grade 1) 24 and 48 hours after applicatlon. In the cornea of the two other animals no alterations were detected.
The iris of the third animal reacted with moderate circumcorneal hyperemia (grade 1) 24 and 48 hours after application. In the iris of the two other animals no alterations were detected.
In the conjunctiva of all three animals hyperemla (grade 1) was observed. In the third rabbit, the finding intensified to diffuse beefy redness of all sectlons (grade 3). 4 days after application redness had completely disappeared in all three rabbits. Slight swelling (grade 1) occurred in all animlas one hour after application. In the third animasl swelling with lids about half closed (grade 2) was observed 24 hours after appllcation. After 72 hours of observation swelling had completely disappeared in all three aninals.
In addition, discharge moistened considerable areas around the eye (grade 3) in animal 2 and 3 immediately after application.
In the first rabbit, dlscharge was only slight (grade 1). 72 hours after injection, these flndings had completely disappeared.
The irritation index is 8. Oxypropazone is therefore classified as non-irritant in this test system.

Other effects:

There were no systemic effects after conjunctival instillation of the test substance
The general condition of the rabbits was indisturbed.

Any other information on results incl. tables

	24 h			48 h			72 h
Animal #	1	2	3	1	2	3	1	2	3
Cornea Opacity	0	0	1	0	0	1	0	0	0
Cornea Area	0	0	2	0	0	2	0	0	0
Iris	0	0	1	0	0	1	0	0	0
Conjunctiva Redness	1	1	3	0	0	2	0	0	1
Conjunctiva Chemosis	0	1	2	0	0	2	0	0	0
Conjunctiva Discharge	0	0	2	0	0	2	0	0	0

Scores 24, 48 and 72 h follwing substance application to one eye according to the Draize scoring system

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test substance is classified as non-irritating in the present test system