Succinimide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2000-05-01 to 2000-09-27

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted 12 February 1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Succinimide

EC Number:

204-635-6

EC Name:

Succinimide

Cas Number:

123-56-8

Molecular formula:

C4H5NO2

IUPAC Name:

pyrrolidine-2,5-dione

Details on test material:

- Name of test material (as cited in study report): "Succinimide"
- Chemical name: 2,5-Diketopyrrolidine
- Lot/batch No.: SMDS 022
- Solubility in water: ca.330 g/L
- Melting point: 123-125 °C
- Boiling point: 287 °C (decomposition)
- pH: 4.5 (50g/L, 20 °C)
- Expiration date of the lot/batch: December 2000
- Storage condition of test material: Room temperature, in the dark
- Stability at storage conditions: Stable.

Specific details on test material used for the study:

OTHER SPECIFICS:
- measurement of pH: 4.4 (1% solution in deionized water, v/v, determined with a pH-Meter)

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga, D-97633
- Age at study initiation: not specified
- Weight at study initiation: Animal No. 1: 2.4 kg, Animal No. 2: 2.4 kg, Animal No. 3: 2.5 kg
- Housing: Optimal hygienic conditions, individual caging in metal wire cages, Ehret GmbH, type KK016R, 79 cm x 59 cm x 35 cm
- Diet: Altromin 2023 diet for rabbits, ad libitum
- Water: tap water from an automatical watering system, ad libitum
- Acclimation period: 5 days (animal No. 1) and 12 days (animals No. 2 and No. 3)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): average of 20 °C
- Humidity (%): average of 51 %
- Air changes (per hr): 12 per hour
- Photoperiod (hrs dark / hrs light): 12 hrs dark, 12 hrs lightw

Test system

Vehicle:

water

Controls:

not required

Amount / concentration applied:

The approximate equivalent of 0.1 mL of the test substance was administered per animal into the conjuctival sacs of the right eyes.
The weighed amounts of the individual doses were 97.89 and 95 mg.

Duration of treatment / exposure:

single treatment

Observation period (in vivo):

Both eyes of the animals were examined within 24 hours before instillation and approximately 1, 24, 48 and 72 hours p.a.

Number of animals or in vitro replicates:

3 females

Details on study design:

The approximate equivalent of 0.1 mL of the test substance was administered per animal into the conjunctival sacs of the right eyes by gently pulling the lower lids away from the eyeballs for instillation. The eyes were held closed for about one second to prevent loss of test substance.
The left eyes remained untreated and served as a control.
Firstly, the test substance was administered to one animal. As no evidence for a serious damage to the eye of this animal was found during the initial 72-hour observation period (no corrosive effect), the test substance was administered to the other two animals subsequently.

Both eyes of the animals were examined within 24 hours before the instillation and approximately 1, 24, 48 and 72 hours p.a.
Additional examinations were performed 6 days after the instillation.
The whole eyes, especially the corneae, the irises and the conjunctivae were examined using an otoscope lamp. Eye irritation was scored and recorded according to the method of Draize (see in box "Any other information on materials & methods incl. tables")

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 6 days

Remarks on result:

positive indication of irritation

Results 8

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 6 days

Remarks on result:

positive indication of irritation

Results 9

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 6 days

Remarks on result:

positive indication of irritation

Results 10

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Results 11

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 6 d

Remarks on result:

no indication of irritation

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

All untreated eyes ("control eyes") were normal at any observation time.
Cornea and Iris: Not affected
Conjunctivae, redness: All animals were affected with scores of "1" from 1 h p.a. onwards to 72 h p.a.
Conjunctivae, chemosis: All animals were affected with scores of "1" from 1 h p.a. onwards to a maximum of 24 h p.a.
For individual results see Table 1 in box "Any other information on results incl. tables".

Other effects:

None

Any other information on results incl. tables

 Table 1: Individual eye irritation scores             

							Conjunctivae
Time after instillation (p.a.)	Corneae animal No.			Irises animal No.			Redness animal No.			Chemosis animal No.
	1	2	3	1	2	3	1	2	3	1	2	3
1 h	0	0	0	0	0	0	1	1	1	1	1	1
24 h	0	0	0	0	0	0	1	1	1	0	1	0
48 h	0	0	0	0	0	0	1	1	1	0	0	0
72 h	0	0	0	0	0	0	1	1	1	0	0	0
mean (24-72 h)	0.0	0.0	0.0	0.0	0.0	0.0	1.0	1.0	1.0	0.0	0.3	0.0
6 d	0	0	0	0	0	0	0	0	0	0	0	0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In this study, the test substance succinimide is not irritating to the eyes. All observed effects on conjunctivae redness and chemosis were reversible within 6 days.

Executive summary:

In a primary eye irritation study conducted according to OECD guideline 405, 0.1 mL of succinimide was instilled into the conjunctival sac of one eye of 3 female New Zealand White rabbits. Animals then were observed of 6 days. Irritation was scored by the method of Draize. Irritant effects on cornea and iris were not observed at any observation point in any animal. Conjunctivae redness is observed in all animals as well as some injected blood vessels were observed from 1 h onwards until 72 h p.a. Very slight swelling was seen in all animals from 1 h onwards until a maximum of 24 h p.a. All effects were fully reversible within 6 days.

In this study, succinimide is not an eye irritant according to CLP criteria.