Cyclohexanone, peroxide

Endpoint summary

Description of key information

Based on the available studies the substance is severely irritating to rabbit skin and corrosive to the eye.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

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:

other: Adequate details however 24 hour exposure; no COA; non-GLP. Needs test article id statement

Qualifier:

equivalent or similar to guideline

Guideline:

other: USA Federal Hazardous Substances Act (US-FHSA),

Deviations:

not specified

Principles of method if other than guideline:

USA Federal Hazardous Substances Act (US-FHSA),

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

None provided.

Type of coverage:

occlusive

Preparation of test site:

other: shaved and abraded

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.5 ml

Duration of treatment / exposure:

24 hours

Observation period:

24 and 72 hours after application

Number of animals:

Six rabbits are treated on intact ski and six on abraded skin

Details on study design:

Twelve healthy adult New Zealand White albino rabbits are used for 1-4 test substances. Twenty four hours prior to applying the materials, hair is removed from the backs of the animals with an electric clipper in such a way as to avoid abrasions.
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. 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 maintain the test patches in position and to retard evaporation of volatile substances.
Six rabbits are treated on the intact skin, the other six on the abrades. The abrasions are minor incisions through the stratum corneum, but not sufficiently deep to disturb the derma or the product bleeding.
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).
In the case of surface active test substances the skin reactions after 72 hours usually consist of scaliness and/or necrosis,. Since the Draize grading system does not comprise these abnormalities the second reading is carried out on the basis of the laboratory's own grading system.

Irritation parameter:

overall irritation score

Remarks:

Erythema plus edema

Basis:

mean

Time point:

24 h

Score:

6.7

Max. score:

8

Reversibility:

other: No data reported

Remarks on result:

other: Intact skin

Irritation parameter:

overall irritation score

Remarks:

erythema

Basis:

mean

Time point:

72 h

Score:

2

Max. score:

8

Reversibility:

other: No data reported

Remarks on result:

other: intact skin

Irritation parameter:

overall irritation score

Remarks:

erythema and edema

Basis:

mean

Time point:

24 h

Score:

6.8

Max. score:

8

Reversibility:

other: No data reported

Remarks on result:

other: abraded skin

Irritation parameter:

overall irritation score

Remarks:

erythema

Basis:

mean

Time point:

72 h

Score:

2

Max. score:

8

Reversibility:

other: No data reported

Remarks on result:

other: abraded skin

Irritant / corrosive response data:

After 24 hours: distinct ischemia and slight or moderate edema.
After 72 hours: very slight to distinct scaliness or incrustation.

Interpretation of results:

Category 1B (corrosive) based on GHS criteria

Conclusions:

The test substance is a severe to very severe primary skin irritant.

Executive summary:

The test article was evaluated for its potential skin irritation potential. The test article was applied to the intact and abraded skin of rabbits for 24 hours and the reactions scored according to the Draize method 24 and 72 hours following application.

The test article was severely irritating to rabbit skin.

Reference 2

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

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:

other: Adequate details; no COA; non-GLP. Needs test article id statement

Qualifier:

equivalent or similar to guideline

Guideline:

other: FDA - Draize Test

Deviations:

not specified

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

None provided.

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

One tenth of a milliliter

Observation period (in vivo):

The eyes are examined at 24, 48, 72 hours and 7 days after instillation of the test material.

Number of animals or in vitro replicates:

one

Details on study design:

The eyes of the animals are examined before testing and only those animals without observable eye defects are used. On tenth of a milliliter of the test substance is allowed to fall on the everted lower lid of one eye of each rabbit; the upper and lower eye lid are then carefully closed and subsequently held together for at least one second before releasing to prevent loss of material. The other eye remaining untreated serves as a control. The eyes are not washed following installation and the animals are released immediately.

The eyes are examined at 24, 48, 72 and 7 days after instillation of the test material.

An animal is considered as giving a positive reaction if there is, at any of the readings, discernible opacity of the cornea (other than a slight dulling of the normal lustre), or ulceration of the cornea, or inflammation of the iris (other than a slight deepening of the folds (rugae) or a slight circumcorneal injection), or if such substances produce in the conjunctivae (palpebral and bulbar, excluding the cornea and iris) an obvious swelling with partial eversion of the lids, or a diffuse deep-crimson red with individual vessels not easily discernible. The FDA scoring scale was used.

Ocular reactions are read using a binocular magnifying glass. The diagnosis of corneal damage is confirmed if necessary by staining the eyes of the animals with fluorescein-impregnated papers. After flushing the excess fluorescein solution, the eyes are examined in a dark room under ultraviolet illumination.

A substance which has elicited corneal and/or iris lesions which have not cleared by the seventh day reading, is considered a severe eye irritant.

Irritation parameter:

cornea opacity score

Basis:

animal: only one animal used

Time point:

24 h

Score:

3

Max. score:

4

Reversibility:

not reversible

Remarks:

after 7 days

Irritation parameter:

iris score

Basis:

animal: only one animal used

Time point:

24 h

Score:

1

Max. score:

2

Reversibility:

not reversible

Remarks:

after 7 days

Irritation parameter:

conjunctivae score

Basis:

animal: only one used

Time point:

24 h

Max. score:

3

Reversibility:

not reversible

Remarks:

after 7 days

Remarks on result:

other: conjunctivae were necrotic

Irritation parameter:

chemosis score

Basis:

animal: only one used

Time point:

24 h

Score:

3

Max. score:

4

Reversibility:

not reversible

Remarks:

after 7 days

Irritation parameter:

cornea opacity score

Basis:

animal: only one used

Time point:

48 h

Score:

3

Max. score:

4

Reversibility:

not reversible

Remarks:

after 7 days

Irritation parameter:

iris score

Basis:

animal: only one used

Time point:

48 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal: only one used

Time point:

48 h

Max. score:

3

Reversibility:

not reversible

Remarks:

after 7 days

Remarks on result:

other: conjunctivae were necrotic

Irritation parameter:

chemosis score

Basis:

animal: only one used

Time point:

48 h

Score:

3

Max. score:

4

Reversibility:

not reversible

Remarks:

after 7 days

Irritation parameter:

cornea opacity score

Basis:

animal: only one used

Time point:

72 h

Score:

>= 3 - <= 4

Max. score:

4

Reversibility:

not reversible

Remarks:

after 7 days

Irritation parameter:

iris score

Basis:

animal: only one used

Time point:

72 h

Score:

0

Max. score:

2

Remarks on result:

other: i

Irritation parameter:

conjunctivae score

Basis:

animal: onnly one used

Time point:

72 h

Max. score:

3

Reversibility:

not reversible

Remarks:

after 7 days

Remarks on result:

other: conjunctivae were necrotic

Irritation parameter:

chemosis score

Basis:

animal: only one used

Time point:

72 h

Score:

3

Max. score:

4

Reversibility:

not reversible

Remarks:

after 7 days

Irritation parameter:

cornea opacity score

Basis:

animal: only one used

Time point:

7 d

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks:

after 7 days

Irritation parameter:

iris score

Basis:

animal: only one used

Time point:

7 d

Remarks on result:

other: iris not discernable

Irritation parameter:

conjunctivae score

Basis:

animal: only one used

Time point:

7 d

Max. score:

3

Reversibility:

not reversible

Remarks:

after 7 days

Remarks on result:

other: conjunctivae were necrotic

Irritation parameter:

chemosis score

Basis:

animal: only one used

Time point:

7 d

Score:

3

Max. score:

4

Reversibility:

not reversible

Remarks:

after 7days

Irritant / corrosive response data:

Moderate to complete corneal opacity, slight iritis,
necrosis of the conjunctivae and swelling with lids
about half closed.
The ocular lesions suggested permanent blindness.

Interpretation of results:

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

Conclusions:

The test article caused very severe irreversible eye damage.

Executive summary:

The test article was evaluated for potential eye irritation. One tenth of a milliliter was instilled into one eye of one rabbit. Reactions were evaluated at 24,48, 72 hours and 7 days following instillation.

The test article induced very severe irreversible eye damage.

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the available studies the substance is severely irritating to rabbit skin and corrosive to the eye. The harmonized classification for the substance is corrosive to skin and eye, category 1b and 1, respectively.