Bis(2-ethylhexyl) fumarate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1 April 1999 to 14 July 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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:

Bis(2-ethylhexyl) fumarate

EC Number:

205-448-2

EC Name:

Bis(2-ethylhexyl) fumarate

Cas Number:

141-02-6

Molecular formula:

C20H36O4

IUPAC Name:

bis(2-ethylhexyl) but-2-enedioate

Details on test material:

- Name of test material (as cited in study report): dioctylfumarate
- Physical state: liquid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Species and strain: Rabbits, New Zealand White
Supplier: J. Schitkovits, A-2620 Natschbach
Number and sex: 3 females
Body weight (at the start and at the termination of the test):
Animal No. 11: 2.9 kg and 3.0 kg.
Animal No. 12: 3.0 kg and 3.0 kg.
Animal No. 13: 3.3 kg and 3.5 kg.

Hygiene : Optimal hygienic conditions.
Room number: EH1-17.
Room temperature: Average of 20 °C.
Relative humidity: Average of 57 %.
Air exchange: 12 per hour.
Light: Artificial light from 6 a.m. to 6 p.m.
Cages: Individual caging in metal wire cages, Ehret GmbH, D-79312 Emmendingen, type KK 016R, 79 cm x 59 cm x 35 cm.
Feed: Altromin 2023 diet for rabbits, ad libitum. Random samples of the feed are analysed for contaminants by Altromin, D-32791 Lage.
Water: Tap water from an automatic watering system, ad libitum.
Identification: Labelling with a felt-tipped pen in an auricle.
Acclimatisation: 8 days (animal No. 11) and 15 days (animals No. 12 and No. 13).

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.1 mL per animal

Observation period (in vivo):

1, 24, 48 and 72 hours

Number of animals or in vitro replicates:

3

Details on study design:

0.1 ml of the test substance was administered into the conjunctival sac of the right eye by gently pulling the lower lid away from the eyeball for instillation. The eye was held closed for about one second to prevent loss of test substance. The left eye remained untreated and served as a control.
Firstly, the test substance was given to one animal. As there was no evidence for a serious damage to the eye of this animal noted until 72 h p.a., the test substance was administered to the other two animals too.

Both eyes of the animals were examined within 24 hours before the instillation and approximately 1, 24, 48 and 72 hours p.a.
No examinations were performed thereafter.
The scoring terms of 24, 48 and 72 h after the instillation were decisive for the interpretation of the results and the conclusion of the study.
The whole eye, especially the cornea, the iris and the conjunctivae were examined, using an otoscope lamp. Eye irritation was scored and recorded using the scheme for eye lesions.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

not specified

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 72h

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.2

Max. score:

4

Reversibility:

fully reversible within: 48h

Irritant / corrosive response data:

All eyes, treated with the test substance ("test eyes") were normal before the instillation.
All untreated eyes ("control eyes") were normal at any observation time.
Test eyes:
Corneae and Irises: Only scores of "0", i.e. normal, were noted in all animals at all examination terms.
Conjunctivae, redness: All animals were affected with a score of "1" from 1 h p.a. to a maximum of 48 h p.a. No changes were observed later on.
Conjunctivae, chemosis: 2/3 animals were affected with a score of "1" from 1 h p.a. to a maximum of 24 h p.a. No lesions were seen at the other animal and the other examination terms.

Other effects:

None

Any other information on results incl. tables

Table 1: Individual Irritation Scores

	Mean Scores for Animal No.:
	11	12	13
Cornea:	0.0	0.0	0.0
Iris:	0.0	0.0	0.0
Conjunctivae, redness:	0.7	0.7	0.7
Conjunctivae, chemosis:	0.0	0.3	0.3

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test substance caused slight transient ocular irritation. Based on the mean scores calculated from the individual examinations performed 24, 48 and 72 h p.a. and referring to Commission Directive 2001/59/EC the test substance does not require classification for eye irritation.

Executive summary:

 

Aim of the study

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 conformance with the OECD-Guideline 405 and the Directive 92/69/EEC, method B.5.

Administration of the test substance

0.1 mL of "DIOCTYLFUMARAT" was instilled into the conjunctival sac of one eye of each of 3 rabbits.

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 p.a.

Results

General signs

No other than ocular alterations were noted.

Eye examination

Cornea and iris were not affected.

Conjunctivae: Some injected blood vessels were observed in all animals and a slight swelling in 2/3 animals until a maximum of 48 hours p.a.

 

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.:

11

12

13

Cornea:

0.0

0.0

0.0

Iris:

0.0

0.0

0.0

Conjunctivae, redness:

0.7

0.7

0.7

Conjunctivae, chemosis:

0.0

0.3

0.3

 

Ocular lesions were reversible in all animals within 72 hours p.a.

  

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