Diethyl acetylsuccinate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23 February - 9 June 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study according to GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

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:

Diethyl acetylsuccinate

EC Number:

214-223-8

EC Name:

Diethyl acetylsuccinate

Cas Number:

1115-30-6

Molecular formula:

C10H16O5

IUPAC Name:

1,4-diethyl 2-acetylbutanedioate

Details on test material:

- Name of test material (as cited in study report): "Diethylacetylsuccinate"- Physical state: Bright yellow liquid.- Lot/batch No.: SLBE 101- Solubility in water: ca. 15g/L- Melting point: -8 °C- Boiling point: 180 °C/67 mbar- Density: 1.081- Expiration date of the lot/batch: December 1999- Storage condition of test material: In the refrigerator, in the dark.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS- Source: J. Schitkovits, A-2620 Natschbach- Weight at study initiation: Animal No. 1: 3.4 kg, Animal No. 2: 2.8 kg, Animal No. 3: 2.8 kg- Weith at study termination: Animal No. 1: 3.5 kg, Animal No. 2: 3.0 kg, Animal No. 3: 2.8 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 rabbtis, ad libitum.- Water: tap water from an automatical watering system, ad libitum.- Acclimation period: 10 days (animal No. 51) and 16 days (animals No. 52 and No. 53)ENVIRONMENTAL CONDITIONS- Temperature (°C): average of 20 °C - Humidity (%): average of 55 %.- Air changes (per hr): 12 per hour.- Photoperiod (hrs dark / hrs light): 12 hrs dark, 12 hrs light.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.1 mLof the test substance was administered to the conjuctival sac of the right eye. The eye was held closed for about one second to prevent loss of the test substance.

Observation period (in vivo):

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

Number of animals or in vitro replicates:

3 females

Details on study design:

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.No further examinations were performed thereafter. The whole eyes, especially the corneae, the irises and the conjunctivae were examined using an otoscope lamp. Eye irritation was scored and recorded using the scheme for eye lesions (see below).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

all animals

Time point:

other: 1, 24, 48, 27 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

all animals

Time point:

other: 1, 24, 48, 72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 1, 24, 48, 72 h

Score:

0

Max. score:

3

Reversibility:

other: not applicable

Results 4

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 1 h p.a.

Score:

1

Max. score:

3

Reversibility:

fully reversible

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

3

Reversibility:

other: not applicable

Results 6

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: 1 h and 24 h p.a.

Score:

1

Max. score:

3

Reversibility:

fully reversible

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: 48, 72 h

Score:

0

Max. score:

3

Reversibility:

other: not applicable

Results 8

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

all animals

Time point:

other: 1, 24, 48, 72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritant / corrosive response data:

All untreated eyes ("control eyes") were normal at any observation time.Cornea and Iris: only scores of 0 (normal) were noted in all animals at all examination terms.Conjunctivae, redness: 2/3 were affected 1 h p.a. with a score of 1, 1/3 animals had a score of 1 also 24 h p.a.Conjunctivae, chemosis: No lesions were seen at the observation terms.

Other effects:

None

Any other information on results incl. tables

 

	Mean Scores (24, 48, 72 h) for Animal No.:
	1	2	3
Cornea:	0.0	0.0	0.0
Iris:	0.0	0.0	0.0
Conjunctivae, redness:	0.0	0.0	0.3
Conjunctivae, chemosis:	0.0	0.0	0.0

Individual data

 Examination of corneae, irises and conjunctivae. Individual data and means.
              

							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	0	1	1	0	0	0
24 h	0	0	0	0	0	0	0	0	1	0	0	0
48 h	0	0	0	0	0	0	0	0	0	0	0	0
72 h	0	0	0	0	0	0	0	0	0	0	0	0
mean (24-72 h)	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.3	0.0	0.0	0.0

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated informationCriteria used for interpretation of results: EU

Conclusions:

No classification of "Diethylacetylsuccinate" is derived from the results of this study.

Executive summary:

The aim of this study was to investigate possible irritating or corrosive effects of the test substance following a single administration into the conjunctival sac of one eye of rabbits.

Methods

Methods and investigations were performed in accordance with the OECD-Guideline 405 and the Directive 92/69/EC, method B.5.

Administration of the test substance

0.1 mL of "diethylacetylsuccinate" was instilled into the conjunctival sac of one eye of each of 3 New Zealand White rabbits. Firstly the test substance was administered to one animal.

Investigations

·     Body weights: at the start and at the termination of the test.

·     General signs of toxicity: once daily.

·     Eye examination: 1, 24, 48 and 72 h after the administration (p.a.) of the test substance.

Results

General signs

No other than ocular lesions were noted.

Eye examination

·     Corneae and irises: Not affected at any observation point.

·     Conjunctivae: Some injected blood vessels were observed in 2/3 animals 1 h p.a. and lasted until a maximum of 24 h p.a. No lesions were observed at the other examination terms.

   

Conclusion

The following mean scores were calculated for each animal from the individual examinations performed 24 h, 48 h and 72 h p.a.:

 

	Mean Scores for Animal No.:
	1	2	3
Cornea:	0.0	0.0	0.0
Iris:	0.0	0.0	0.0
Conjunctivae, redness:	0.0	0.0	0.3
Conjunctivae, chemosis:	0.0	0.0	0.0

 

Mean scores calculated from the examnations 24, 48 and 72 hours p.a., are clearly below the threshold for a classification of the test substance as "irritant". No classifciation of "diethylacetylsuccinate" is therefore derived from the results of this study.