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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:
1978
Report date:
1978

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Principles of method if other than guideline:
In general the techniques of tests as published by FDA of United States (Fed. Reg. 28 (119), 5582, 1963) and Draize and Kelly (Drug Cosemt. Industr. 71 (1952)36) are followed.
In the present study some rabbits had their eyes rinsed out after instillation of the test materials.
The numbers of animals used for each substance and the time between instillation and irrigation were dependent on the eye effects of the various substances. The obversation periods were, also dependent on the eye effects, prolonged to a maximum of five weeks.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2-[(2-hydroperoxybutan-2-yl)peroxy]butane-2-peroxol; butane-2,2-diperoxol
EC Number:
700-954-4
Cas Number:
1338-23-4
Molecular formula:
Mixture of C4H10O4 and C8H18O6
IUPAC Name:
2-[(2-hydroperoxybutan-2-yl)peroxy]butane-2-peroxol; butane-2,2-diperoxol

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Six New Zealand White albino rabbits are used for each test substance. The animals are caged invidividually and received no hay or other extraneous material that might enter the eyes.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The eyes, remaining untreated, serves as a control.
Amount / concentration applied:
One tenth of a milliliter of the test substance is allowed to fall on the everted lower lid of one eye of each rabbit.
Duration of treatment / exposure:
The eyes are not washed following instillation and the animals are released immediately.
Observation period (in vivo):
The eyes are estimated at 24, 48, 72 hours and 7 days after instillation of the test materials.
Number of animals or in vitro replicates:
six
Details on study design:
- An animal is considered as giving a positive reaction if there is, at any of the readings, discernable opacity of the cornea or ulceration of cornea, or inflammation of the iris or if such substances produce in the conjunctivae an obvious swelling with partial eversion of lids, or a difuse deep-crimson red with inidividual vessels not easily discernable.
- The test is considered positive if four or more of the animals in the test group of six rabbits exhibit a positive reaction. If one animal exhibits a positive reaction, the test is regarded as negative.
- If two or three animals exhibit a positive reaction, the test is repeated, using a different group of six animals.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal 1
Time point:
24/48/72 h
Score:
3.33
Max. score:
4
Remarks on result:
other: eye not rinsed
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal 1
Time point:
24/48/72 h
Score:
1
Max. score:
2
Remarks on result:
other: eye not rinsed
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Remarks:
animal 1
Time point:
24/48/72 h
Score:
1.67
Max. score:
3
Remarks on result:
other: eye not rinsed
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal 1
Time point:
24/48/72 h
Score:
3
Max. score:
4
Remarks on result:
other: eye not rinsed
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal 3
Time point:
24/48/72 h
Score:
2.33
Max. score:
4
Remarks on result:
other: eyes rinsed after 4 seconds
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal 3
Time point:
24/48/72 h
Score:
1
Max. score:
2
Remarks on result:
other: eyes rinsed after 4 seconds
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Remarks:
animal 3
Time point:
24/48/72 h
Score:
2
Max. score:
3
Remarks on result:
other: eyes rinsed after 4 seconds
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal 3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Remarks on result:
other: eyes rinsed after 4 seconds
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal 4
Time point:
24/48/72 h
Score:
1
Max. score:
4
Remarks on result:
other: eyes rinsed after 4 seconds
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal 4
Time point:
24/48/72 h
Score:
0.67
Max. score:
2
Remarks on result:
other: eyes rinsed after 4 seconds
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Remarks:
animal 4
Time point:
24/48/72 h
Score:
1
Max. score:
3
Remarks on result:
other: eyes rinsed after 4 seconds
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal 4
Time point:
24/48/72 h
Score:
1.67
Max. score:
4
Remarks on result:
other: eyes rinsed after 4 seconds
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal 5
Time point:
24/48/72 h
Score:
2
Max. score:
4
Remarks on result:
other: eye rinsed after 15 seconds
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal 5
Time point:
24/48/72 h
Score:
1
Max. score:
2
Remarks on result:
other: eye rinsed after 15 seconds
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Remarks:
animal 5
Time point:
24/48/72 h
Score:
2
Max. score:
3
Remarks on result:
other: eye rinsed after 15 seconds
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal 5
Time point:
24/48/72 h
Score:
3
Max. score:
4
Remarks on result:
other: eye rinsed after 15 seconds
Irritant / corrosive response data:
The instillation of methyl-ethylketone peroxide into the eye without subsequent rinsing resulted in complete loss of sight within three days. When the eyes were rinsed 4 or 15 seconds after instillation severe ocular lesions ocurred which might result in partial loss of sight.
Other effects:
No information for animal 2 are available. Details see "Any other information on results incl. tables".

Any other information on results incl. tables

Eye effects of methyl-ethylketone peroxide; eye not rinsed:

  

Rabbit number

Cornea

Iris

Conjunctivae (redness)

Conjunctiva

(chemosis)

after 1 day

1

3

1

3

3

after 2 days

1`

3

1

2

3

after 3 days

1``

4

?

-

3

after 7 days

1

Cornea and conjunctivae white-coloured, swollen eyelids

after 14 days

1

Eye-ball white and nearly inrecognizable, swollen eyelids

 

after 21 days

1

Eye-ball white and nearly unrecognizable, swollen eyelids

`) After 2 days nictitating membrane was ischemic

`´) After 3 days iris not discernible and conjunctivae white-coloured

 

Eye effects of methyl-ethylketone peroxide: eyes rinsed after 4 seconds

 

Rabbit number

Cornea

Iris

Conjunctivae (redness)

Conjunctiva

(chemosis)

after 1 day

3

2

1

2

2

4

1

1

1

2

after 2 days

3

2

1

2

2

4

1

0

1

2

after 3 days

3

3

1

2

2

4

1

1

1

1

after 7 days

3`

3

1

1

1

4

0

0

1

1

after 14 days

3`

3

1

1

1

4

0

0

0

0

after 21 days

3

deformed eye-ball (ulcus corneae), moderate to severe corneal opacity, vascularisation of the cornea; iris and conjunctivae without visible damage

4

no visible damage

after 35 days

3

moderate corneal opacity, vascularisation of- and scar tissue on cornea; iris and conjunctivae without visible damage.

4

no visible damage

`) deformed eye-ball (ulcus corneae)

 

 Eye effects of methyl-ethylketone peroxide; rinsed out after 15 seconds

 

Rabbit number

Cornea

Iris

Conjunctivae (redness)

Conjunctiva

(chemosis)

after 1 day

5

2

1

2

3

after 2 days

5

2

1

2

3

after 3 days

5

2

1

2

3

after 7 days

5`

`3

1

2

3

after 14 days

5`

3

1

2

2

after 21 days

5

deformed eye-ball (ulcus corneae), moderate to severe corneal opacity, strongly vascularised fibroangioblastic tissue on cornea; iris and conjunctivae without visible damage

after 35 days

5

severe corneal opacity with pupil barely discernible (still reaction to light), pannus formation on cornea, moderate discharge; iris and conjunctivae without visible damage.

`) deformed eye-ball (ulcus corneae)

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
The present results strongly suggest that undiluted methyl-ethylketone peroxide in DMP is a very severe eye irritant which can cause reduce sight. Rinsing of eyes after treatment with methyl-ethylketone peroxide resulted in some reduction of the irritancy when the delay time was relatively short. The present results indicate that delay time for rinsing should better not exceed 4 seconds for methyl-ethylketone peroxide.
Executive summary:

Methyl-ethylketone peroxide in DMP was examined for eye irritating properties in a study with albino rabbits according to the FDA-standards. The results with methyl-ethylketone peroxide strongly suggest that the test item can cause very severe irriversible ocular lesions which are likely to reduce sight. Rinsing with water resulted in some reduction of the irritancy when the delay time was relatively short.