Maleic anhydride

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1991-06-17 to 1991-08-01

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Reference 2

Reference Type:

review article or handbook

Title:

Maleic Anhydride and Maleic Acid, SIDS Initial Assessment Report For SIAM 18

Author:

OECD SIDS

Year:

2004

Bibliographic source:

OECD SIDS Initial Assessment Report For SIAM 18, Paris, France, 20-23 April 2004

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Maleic anhydride

EC Number:

203-571-6

EC Name:

Maleic anhydride

Cas Number:

108-31-6

Molecular formula:

C4H2O3

IUPAC Name:

2,5-dihydrofuran-2,5-dione

Details on test material:

- Name of test material (as cited in study report): maleic anhydride
- Physical state: white, chrystalline solid
- Storage condition of test material: stored at room temperature (approximately 22°C)

Specific details on test material used for the study:

Maleic anhydride was received June 11, 1991. The test article was a white, crystalline solid and was stored at room temperature.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: the test article was administered undiluted. Individual doses of the test article were weighed onto aluminum foil to facllltate dosing

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Johnson Rabbit Ranch, Wilkinson, IN
- Age at study initiation: 2-3 months
- Weight at study initiation: 1.84 to 2.81 kg
- Housing: individually in stainless steel cages measuring 61.0 x 45.5 x 41.0 cm
- Diet: 150 g of Purina Lab Rabbit Chow HF #5326 per rabbit per day
- Water: reverse osmosis-purified water, ad libitum
- Acclimation period: approximately 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23
- Humidity (%): 54
- Photoperiod (hrs dark / hrs light): 12 / 12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 g of the undiluted test item

Duration of treatment / exposure:

0.1 g of the undiluted test article was placed in the everted lower lid of tte right eye of each rabbit. The lids of all treated eyes were held closed for approximately two seconds following test article administration. The other eye was left untreated.

Observation period (in vivo):

1, 24 and 48 hours following test article administration (according to the study protocol, treated eyes were to be examined a minimum of 72 hours after dosing. However, due to signs of severe ocular irritation, the study was terminated following the 48 hour examination.)

Duration of post- treatment incubation (in vitro):

n.a.

Number of animals or in vitro replicates:

three animals per sex

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no washing

SCORING SYSTEM: According to OECD testing guideline 405 (Draize).

TOOL USED TO ASSESS SCORE: fluorescein and ultraviolet light (after the 1 hr scoring)

OTHER:
- All rabbits were observed daily for mortalIty and morbidity.
- The rabbits were weighed immediately prior to dosing.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24 h

Score:

3.8

Max. score:

4

Reversibility:

not reversible

Results 2

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

48 h

Score:

3.8

Max. score:

4

Reversibility:

not reversible

Results 3

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

72 h

Remarks on result:

not measured/tested

Remarks:

The study was terminated at day 2 due to severe effects/corrosion.

Results 4

Irritation parameter:

iris score

Basis:

mean

Time point:

24 h

Score:

2

Max. score:

2

Reversibility:

not reversible

Results 5

Irritation parameter:

iris score

Basis:

mean

Time point:

48 h

Score:

2

Max. score:

2

Reversibility:

not reversible

Results 6

Irritation parameter:

iris score

Basis:

mean

Time point:

72 h

Remarks on result:

not measured/tested

Remarks:

The study was terminated at day 2 due to severe effects/corrosion.

Results 7

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24 h

Score:

2

Max. score:

3

Reversibility:

not reversible

Results 8

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

48 h

Score:

3

Max. score:

3

Reversibility:

not reversible

Results 9

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

72 h

Remarks on result:

not measured/tested

Remarks:

The study was terminated at day 2 due to severe effects/corrosion.

Results 10

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Results 11

Irritation parameter:

chemosis score

Basis:

mean

Time point:

48 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Results 12

Irritation parameter:

chemosis score

Basis:

mean

Time point:

72 h

Remarks on result:

not measured/tested

Remarks:

The study was terminated at day 2 due to severe effects/corrosion.

Irritant / corrosive response data:

The maximum eye irritation score was 106.7 (out of 110) 48 hours after administration of the test item. For detailed results please refer to Table 1 in box "Any other information on results incl. tables".

Other effects:

No deaths occurred during the study.However, two rabbits were vocal immediately following test article administration and signs of ocular irritation were severe. Therefore, out of concern for the animals' pain and discomfort, the study was terminated following the 48-hour examination.
One animal also developed corneal bulging, an ocular lesion not addressed by the Draize and OECD criteria.

Any other information on results incl. tables

Table 1: Summary of eye irritation score

		Cornea		Iris	Conjunctiva			Sex
Animal	Reading	Opacity	Area involved		Redness	Chemosis	Discharge
1	1 hrs	4	4	2	2	3	3	M
2	1 hrs	4	4	2	2	3	2	M
3	1 hrs	4	4	2	2	4	3	M
4	1 hrs	4	4	2	2	4	2	F
5	1 hrs	4	4	2	2	3	3	F
6	1 hrs	4	4	2	2	4	3	F
1	24 hrs	4	4	2	2	4	3	M
2	24 hrs	4	4	2	2	4	3	M
3	24 hrs	4	4	2	2	4	3	M
4	24 hrs	4	4	2	2	4	3	F
5	24 hrs	3	4	2	2	4	3	F
6	24 hrs	4	4	2	2	4	3	F
1	48 hrs	4	4	2	3	4	3	M
2	48 hrs	4	4	2	3	4	3	M
3	48 hrs	4	4	2	3	4	3	M
4	48 hrs	4	4	2	3	4	3	F
5	48 hrs	3	4	2	3	4	3	F
6	48 hrs	4	4	2	3	4	3	F

Table 2: Total eye irritation score

Total irritation score (according to Draize)
Animal	Reading	Score
1	1 hr	106
2	1 hr	104
3	1 hr	108
4	1 hr	106
5	1 hr	106
6	1 hr	108
1	24 hrs	103
2	24 hrs	108
3	24 hrs	108
4	24 hrs	108
5	24 hrs	88
6	24 hrs	108
1	48 hrs	110
2	48 hrs	110
3	48 hrs	110
4	48 hrs	110
5	48 hrs	90
6	48 hrs	110
mean	1 hr	106.3
mean	24 hrs	104.7
mean	48 hrs	106.7

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

In this study under the given conditions the test item showed severe effects on rabbit eyes

Executive summary:

In a primary eye irritation study, maleic anhydride was administered undiluted at a dose of 0.1 g to the right eye of each of six New Zealand albino rabbits, with the left eye serving as an untreated control. The treated eye of each rabbit was scored for irritation at 1, 24- and 48-hours following test article administration. The control eye was used for comparison.  According to the study protocol, treated eyes were to be examined a minimum of 72 hours after dosing. However, due to signs of severe ocular irritation, the study was terminated following the 48-hour examination. Irritation was scored according to OECD guideline 405 and to the criteria of Draize.

No deaths occurred during the study. However, two rabbits were vocal immediately following test article administration and signs of ocular irritation were severe. Therefore, out of concern for the animals' pain and discomfort, the study was terminated following the 48-hour examination. The maximum eye irritation score was 106.7 (out of a maximum of 110). The mean conjunctival erythema scores at 24 and 48 hours were 2.0 and 3.0, respectively. The mean conjunctival chemosis scores at 24 and 48 hours were 4.0 and 4.0, respectively. The corneal opacity scores at 24 and 48 hours were 3.8 and 3.8, respectively. The iridial lesions scores at 24 and 48 hours were 2.0 and 2.0, respectively.

 

In this study, maleic anhydride showed severe effects on rabbit eyes. Thus, based on the severity of the effects, the test item must be considered as eye damaging. In accordance with ATP13 to CLP Regulation 1272/2008 classification as Eye Dam. 1, H318 is warranted.