2-Butanone, peroxide

Endpoint summary

Description of key information

Methyl-ethylketone peroxide in DMP was tested for skin irritation/corrosion properties in studies with rabbits. Methyl-ethylketone peroxide was corrosive to the skin. Methyl-ethylketone peroxide was tested for eye irritation/corrosion in two studies with rabbits. Methyl-ethylketone peroxide is considered as a corrosive substance.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Qualifier:

according to guideline

Guideline:

other: EEC Directive 79/831, Annex V, Part B: Methods for the determination of toxicity, B.4. Acute toxicity, skin irritation

Deviations:

no

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: adult and healthy

Type of coverage:

occlusive

Preparation of test site:

abraded

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Concentration : 0.5 mL

Duration of treatment / exposure:

24 hours

Observation period:

24 hours and 48 hours

Number of animals:

12 animals

Details on study design:

- Six animals are treated on the intact, the other six animals on the abraded skin.
- Primary irritation to the skin is measured by a patch-test technique on the abraded and intact skin of albino rabbits.
- An amount of 0.5 mL of test substance is brought on the intact or abraded skin under a surgical patch measuring 1 inch x 1 inch. The patches are fixed to the application site by means of adhesive tape and the entire trunk of the rabbits is wrapped with an impervious material to maitain the test patches in position and to retard evaporation of substances.
- After an exposure period of 24 hours the patches and the material applied are removed and the resulting skin reactions are evaluated by the method of Draize (J. Pharmacol. 82 (1944) 377 - 390). A second reading is made 48 hours later (72 hours after application).

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

4

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.8

Max. score:

4

Irritant / corrosive response data:

The dermal effects observed at the end of the 4-hour exposure period were well-defined erythema, slight to moderate ischemia, slight to moderate haemorrhages and severe oedema.

Other effects:

After one week: moderate scaliness to severe incrustation.
After two weeks the old necrotic skin had been ejected.
After eight weeks scar tissue and slightly disturbed hair growth were observed on the application sites.

Individual and average skin irritation scores of methyl-ethylketone peroxide:

 

Rabbit number	Hours after patch removed
	1 hours		24 hours		48 hours		72 hours
	A	B	A	B	A	B	A	B
2059	4	4	4	2	4	2	4	1
2060	4	4	4	2	4	1	4	1
2061	4	4	4	3	4	1	4	1
2062	4	4	4	3	4	1	4	1
2063	4	4	4	3	4	2	4	2
2064	4	4	4	3	4	2	4	2
average	8.0		6.7		5.5		5.3

 

A = erythema

B = oedema

Interpretation of results:

Category 1B (corrosive) based on GHS criteria

Conclusions:

On the basis of the present results, it can be concluded that undiluted methyl-ethylketone peroxide in DMP is corrosive with the skin, under occlusion, for four hours, as scar formation and permanent skin damage was observed.

Executive summary:

Methyl-ethylketone peroxide in DMP was tested in irritation study to skin according to the EEC Directive 79/831, Annex V, Part B, B.4 Acute toxicity, skin irritation. Primary irritation to the skin is measured by patch-test technique on the abraded and intact skin of albino rabbits.

An amount of 0.5 mL of the test substance is brought on the intact or abraded skin under a surgical patch measuring 1 inch x 1 inch. Six rabbits are treated on the intact skin, the other six on the abraded skin. After an exposure period of 24 hours the patches and the material applied are removed and the resulting skin reactions are evaluated by the method of Draize. A second reading is made 72 hours after application. The dermal effects observed at the end of the 4 -hour exposure period considered of well-defined erythema, slight to moderate ischemia, slight to moderate haemorrhages and severe oedema. After one week all application sites generally showed moderate to severe incrustation. After two weeks the old necrotic skin had been ejected. The new skin on the application sites showed moderate scaliness, decreased hair growth and some signs of scar tissue formation. After eight weeks scar tissue and slightly disturbed hair growth were observed on the application sites.

Based on these results, it can be concluded that undiluted methyl-ethylketone peroxide is corrosive to the skin under occlusive test conditions for four hours.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

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

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

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.

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.

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".

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)

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin:

The key study was carried out according to the EEC Directive 79/831, Annex V, Part B, B.4 Acute toxicity, skin irritation. Primary irritation to the skin is measured by patch-test technique on the abraded and intact skin of albino rabbits.

An amount of 0.5 mL of the test substance is brought on the intact or abraded skin under a surgical patch measuring 1 inch x 1 inch. Six rabbits are treated on the intact skin, the other six on the abraded skin. After an exposure period of 24 hours the patches and the material applied are removed and the resulting skin reactions are evaluated by the method of Draize. A second reading is made 72 hours after application. The dermal effects observed at the end of the 4 -hour exposure period considered of well-defined erythema, slight to moderate ischemia, slight to moderate haemorrhages and severe oedema. After one week all application sites generally showed moderate to severe incrustation. After two weeks the old necrotic skin had been ejected. The new skin on the application sites showed moderate scaliness, decreased hair growth and some signs of scar tissue formation. After eight weeks scar tissue and slightly disturbed hair growth were observed on the application sites.

Based on these results, it can be concluded that undiluted methyl-ethylketone peroxide in DMP is corrosive to the skin, under occlusive test conditions, for four hours.

In further rabbit skin tests, a single application of methyl-ethylketone peroxide in DMP to shaved skin resulted in erythema, edema, and vesiculation within 2 or 3 days. The maximal nonirritating concentration was estimated to be 1.5% peroxide. No histopathology was performed in these studies (Zeiger, E; 1993).

Eye:

In the key study, methyl-ethylketone peroxide in DMP was examined for eye irritating properties in a study with albino rabbits (evaluated as Klimisch 2).

The results with methyl-ethylketone peroxide strongly suggest that the test item can cause very severe irriversibleocular lesions which are likely to reduce slight. Rinsing with water resulted in some reduction of the irritancy when the delay time was relatively short.

In a supporting study, six New Zealand White rabbits, equally divided as to sex were used in an eye irritation study. 0.1 mL methyl-ethylketone peroxide in DMP was instilled into one eye and no wash was employed. Based on the results of this study, methyl-ethylketone peroxide would be considered a severe eye irritant and corrosive substance for the corneal surface of the eye.

In further eye tests in rabbits, the maximal nonirritating concentration was estimated to be 0.6% peroxide. However, it was noted that none of the organic peroxides tested caused irritation when the eyes were rinsed within 4 seconds after application (Zeiger, E; 1993).

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on local effects the test item is classified and labelled as corrosive to the skin Cat 1B (H 314 "Causes severe skin burns and eye damage") and eye damaging Cat 1 (H318 "Causes serious eye damage") according to Regulation (EC) No 1272/2008 (CLP), as amended for the seventeenth time in Regulation (EU) No 2021/849.