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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1975
Report date:
1975

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
other: FDA Guideline (Federal Register, Vol. 38, No. 187, 1973
Version / remarks:
1973
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
See section 'Principles of method other than guideline'
Principles of method if other than guideline:
Deviation from OECD guideline 405:
- End of the observation period after 72 hours despite persisting irritation effects.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2-ethylhexyl hydrogen maleate
EC Number:
231-048-2
EC Name:
2-ethylhexyl hydrogen maleate
Cas Number:
7423-42-9
Molecular formula:
C12H20O4
IUPAC Name:
2-ethylhexyl hydrogen maleate
Test material form:
liquid
Specific details on test material used for the study:
The product was a clear oily liquid

Test animals / tissue source

Species:
rabbit
Strain:
Himalayan
Remarks:
SPF-Albino-Himalayan rabbits
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Housing: Singly caged
- Diet: ERKA 8300 (Robert Koch oHG/Hamm), ad libitum.
- Water: Tap water, ad libitum

Test system

Vehicle:
other: sesame oil
Controls:
yes
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 mL
- Concentration: undiluted and as a 10%, 1% solution.

Duration of treatment / exposure:
Single application (24 h).
Observation period (in vivo):
Undiluted test item: 1 h, 7 h, 24 h, 48 h and 72 h
10% test item solution: 1 h, 7 h, 24 h and 72 h
1% test item solution: 1 h, 7 h and 24 h
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: Yes, all eyes were rinsed with physiological NaCl-solution.
- Time after start of exposure: 24 h

SCORING SYSTEM: Draize scheme

OTHER INFORMATION:
The appraisal was carried out with a magnifying glass (binocular) or slit lamp. After the 24-hour observation, all further observations were made after instillation of one drop of fluorescein in the dilution 1: 10000 (= 0.01%) directly on the cornea. Cornea damage appeared yellow. They were most visible in the dimmed room under UV light. After collecting the 24-hour report, all eyes were rinsed with physiological NaCl solution.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
other: Due to strong signs of irritation, the animals were killed after 72 hours.
Remarks on result:
other: undiluted test item
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: Due to strong signs of irritation, the animals were killed after 72 hours.
Remarks on result:
other: undiluted test item
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
other: Due to strong signs of irritation, the animals were killed after 72 hours.
Remarks on result:
other: undiluted test item
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
other: Due to strong signs of irritation, the animals were killed after 72 hours.
Remarks on result:
other: undiluted test item
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48 h
Score:
0
Max. score:
4
Remarks on result:
other: 10% test item solution
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48 h
Score:
0
Max. score:
2
Remarks on result:
other: 10% test item solution
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48 h
Score:
1
Max. score:
3
Reversibility:
other:
Remarks on result:
other: 10% test item solution
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48 h
Score:
2
Max. score:
4
Reversibility:
other:
Remarks on result:
other: 10% test item solution

Any other information on results incl. tables

Table 1: Results of the individual animals (undiluted test item concentration)

Rabbit No.

Irritation parameter

Hours

1

7

24

48

72

394

Cornea opacity score

1

1

1

1

1

Iris score

0

0

0

0

0

Conjunctivae score

2

3

3

3

3

Chemosis score

2

3

4

4

4

393

Cornea opacity score

1

1

1

1

1

Iris score

0

0

0

0

0

Conjunctivae score

2

3

3

3

3

Chemosis score

2

3

4

4

4

392

Cornea opacity score

1

1

1

1

1

Iris score

0

0

0

0

0

Conjunctivae score

2

3

3

3

3

Chemosis score

2

3

4

4

4

391

Cornea opacity score

2

2

2

2

2

Iris score

0

0

0

0

0

Conjunctivae score

2

3

3

3

3

Chemosis score

2

4

4

4

4

390

Cornea opacity score

2

2

2

2

2

Iris score

0

0

0

0

0

Conjunctivae score

2

3

3

3

3

Chemosis score

2

4

4

4

4

389

Cornea opacity score

1

1

1

1

1

Iris score

0

0

0

0

0

Conjunctivae score

2

3

3

3

3

Chemosis score

2

4

4

4

4

Table 2: Results of the individual animals (10% test item concentration)

Rabbit No.

Irritation parameter

Hours

1

7

24

48

301

Cornea opacity score

0

0

0

0

Iris score

0

0

0

0

Conjunctivae score

1

1

1

1

Chemosis score

2

2

2

2

302

Cornea opacity score

0

0

0

0

Iris score

0

0

0

0

Conjunctivae score

1

1

1

1

Chemosis score

2

2

2

2

303

Cornea opacity score

0

0

0

0

Iris score

0

0

0

0

Conjunctivae score

1

1

1

1

Chemosis score

2

2

2

2

304

Cornea opacity score

0

0

0

0

Iris score

0

0

0

0

Conjunctivae score

1

1

1

1

Chemosis score

2

2

2

2

305

Cornea opacity score

0

0

0

0

Iris score

0

0

0

0

Conjunctivae score

1

1

1

1

Chemosis score

2

2

2

2

306

Cornea opacity score

0

0

0

0

Iris score

0

0

0

0

Conjunctivae score

1

1

1

1

Chemosis score

2

2

2

2

Table 3: Results of the individual animals (1% test item concentration)

Rabbit No.

Irritation parameter

Hours

1

7

24

301

Cornea opacity score

0

0

0

Iris score

0

0

0

Conjunctivae score

0

0

0

Chemosis score

0

0

0

302

Cornea opacity score

0

0

0

Iris score

0

0

0

Conjunctivae score

0

0

0

Chemosis score

0

0

0

303

Cornea opacity score

0

0

0

Iris score

0

0

0

Conjunctivae score

0

0

0

Chemosis score

0

0

0

304

Cornea opacity score

0

0

0

Iris score

0

0

0

Conjunctivae score

0

0

0

Chemosis score

0

0

0

305

Cornea opacity score

0

0

0

Iris score

0

0

0

Conjunctivae score

0

0

0

Chemosis score

0

0

0

306

Cornea opacity score

0

0

0

Iris score

0

0

0

Conjunctivae score

0

0

0

Chemosis score

0

0

0

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Application of the undiluted test item resulted in strong irritation to the eyes of all rabbits. Because of these serious injuries, the animals were prematurely withdrawn after 72 hours. The 10% dilution gave a slight reddening and increased swelling of the conjunctiva. The 1% dilution was tolerated without irritation. Based on the results of this eye irritation study, the test item is considered to be irritating to the eyes.
Executive summary:

The eye irritation potential of the test substance was investigated in a study according to FDA guideline (Federal Register, Vol. 38, No. 187, 1973) and which is equivalent to OECD guideline 405. The undiluted test substance as well as a 10% and 1% solution of the test substance in sesame oil was instilled into one eye of six albino Himalayan rabbits. The other untreated eye served as control. The eyes were washed with physiologic NaCl solution after 24 h. The eyes treated with the undiluted test item were assessed for irritation after 1 h, 7 h, 24 h, 48 h and 72 h. The eyes treated with 10% test item solution were observed for 48 h and the eyes treated with 1% test item solution were assessed for 24 hours.

The application of the undiluted substance resulted in strong irritation to the eyes of all rabbits. Due to strong signs of irritation, the animals were killed after 72 hours. The 10% dilution revealed a slight redness and a strong swelling of the conjunctiva. The 1% dilution was tolerated without irritation.

According to OECD guideline, the rabbits' eyes are normally assessed for a 21 days observation period. Therefore, the reversibility of the effects cannot be assessed. Based on the results of this eye irritation study, the test item is considered to be irritating to the eyes. As a worst case consideration, it must be assumed that the effects are not reversible and the substance has to be classified as skin irritating, cat. 1 (H 318).