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Diss Factsheets

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
Study period:
25 April 1984 to 16 May 1984
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984
Report date:
1984

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Remarks:
GLP was not yet legally implemented when the study was conducted.

Test material

Constituent 1
Chemical structure
Reference substance name:
Fumaric acid
EC Number:
203-743-0
EC Name:
Fumaric acid
Cas Number:
110-17-8
Molecular formula:
C4H4O4
IUPAC Name:
but-2-enedioic acid
Test material form:
solid: particulate/powder
Details on test material:
- Physical state: Solid
- Analytical purity: 99.5%
- Odour: Odourless
- Name of test material (as cited in study report): Fumaric acid
- Impurities (identity and concentrations): Benzoic, maleic and phthalic acid < 0.05 %
- Stability under test conditions: No data
- Storage condition of test material: No data
- Other:
pH 2.1 at 4.9 g/L
Density 1.63 g/cm³

Test animals / tissue source

Species:
rabbit
Strain:
other: small white Russian
Details on test animals or tissues and environmental conditions:
Male and female rabbits between 1.9 and 2.1 kg were housed in individual stainless steel cages and acclimated for 14 days. Rabbits received K4 single diet for rabbits (Ssniff Special Feed GmbH) and water ad libitum. Room temperature was 20C with 60% relative humidity. Air was exchanged 15 times per hour and a 12 hr light-dark cycle was employed.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
0.1 g fumaric acid
Duration of treatment / exposure:
The test material was not washed out.
Observation period (in vivo):
1, 24, 48 and 72 hours and 5, 7, 9, 12, 15, 19 and 21 days.
Number of animals or in vitro replicates:
3 males and 3 females
Details on study design:
Test material was applied to the lower conjunctival sac of the right eye by pulling away the lower eyelid. The left eye was treated in one animal.
The contralateral eye served as a concurrent, inherent control.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0.28
Max. score:
2
Reversibility:
not reversible
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
2.83
Max. score:
3
Reversibility:
fully reversible within: 19d
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
1.72
Max. score:
4
Reversibility:
fully reversible within: 19 d
Remarks on result:
positive indication of irritation

Any other information on results incl. tables

Table 1:Cornea evaluation: Degree of opacity (A) × extent of opacity (B) × 5

 

 

1 h

24 h

48 h

72 h

Animal #

Sex

A

B

A × B × 5

A

B

A × B × 5

A

B

A × B × 5

A

B

A × B × 5

1

M

1

4

20

1

4

20

1

4

20

1

4

20

2

M

1

4

20

1

4

20

1

4

20

2

4

40

3

M

2

4

40

2

4+

40

2

4+

40

3

2–

30

4

F

2

4

40

3

2

30

4

2–

40

4

2–

40

5

F

2

4

40

1

4+

20

4

2-

40

3

2–

30

6

F

1

4

20

1

4

20

1

4

20

1

4

20

Mean

 

 

 

30

 

 

25

 

 

30

 

 

30

*) Circular streak (0–4 mm) on the pupil;

+ Spot on the cornea with opacity up to white coloration;

– Remaining surface: reduction in normal clarity

 

Table 2:Iris evaluation: A = Change

 

 

1 h

24 h

48 + 72 h

Animal #

Sex

A

A × 5

A

A × 5

A

A × 5

1

M

0

0

0

0

0

0

2

M

0

0

0

0

0

0

3

M

0

0

0

0

1*

5

4

F

0

0

0

0

0

0

5

F

0

0

1*

5

1*

5

6

F

0

0

0

0

0

0

Mean

 

 

0

 

0.83

 

1.67

*) Circumcorneal injection

 

Table 3:Conjunctive evaluation: Redness (A) + swelling (B) + exudation (C)

 

 

1 h

24 h

48 h

72 h

Animal #

Sex

A

B

C

(A + B + C) × 2

A

B

C

(A + B + C) × 2

A

B

C

(A + B + C) × 2

A

B

C

(A + B + C) × 2

1

M

2

2

2

12

3

2

2

14

3

1

2

12

3

1

1

10

2

M

2

3

2

14

3

2

2

14

2

2

2

12

3–

2

1

12

3

M

2*

3

2

14

2

2

2

12

3–

2

2

14

3–

2

1

12

4

F

2

3

2

14

3+

2

3

16

3

2

3

16

3–

2

2

14

5

F

2*

2

2

12

2

2

2

12

3

1

2

12

3–

1

2

12

6

F

2

2

2

12

3

2

2

14

3

2

2

14

3

1

2

12

Mean

 

 

 

 

13

 

 

 

13.37

 

 

 

13.33

 

 

 

12

*) Necrotic spots on mucous membrane;

+ Skin-like mucous on the cornea;

– White layer is exuded from the mucous membrane

 

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
This study supports the conclusion that fumaric acid is an eye irritant.
Executive summary:

Application of 0.1 g fumaric acid to the eyes of male and female rabbits was considered irritating to the eye and ocular mucous membrane. Fumaric acid is classified as an eye irritant. It is assigned the symbol Xi and the risk-phrase R36 - irritating to the eyes according to Directive 67/548/EEC. It is assigned the pictogram GHS07 with the signal word warning and the hazard statement H319 "causes serious eye irritation".