Registration Dossier

Administrative data

Description of key information

Di-(4-tert-butylcyclohexyl)peroxydicarbonate is not irritating in primary skin and eye irritation tests according to Draize (1944) and FDA-standards (1963), respectively, when applied at a concentration of 0.5 g to the abraded and the intact skin or of 0.1 g instilled into the eyes of albino rabbits.

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
Study period:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: meets generally accepted scientific standards, well documented and acceptable for assessment
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
: exposure 24 hours instead of 4 hours; 12 animals were used
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: adults
Type of coverage:
occlusive
Preparation of test site:
other: abraded and intact skin
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
Duration of treatment / exposure:
24 h
Observation period:
observation 24 h and 72 h after exposure
Number of animals:
12
Details on study design:
TEST SITE
- Area of exposure: 1 inch x 1 inch
- % coverage: no data
- Type of wrap if used: surgical patch fixed by adhesive tape, wrapped with impervious material

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no washing
- Time after start of exposure: patch and material are removed after 24 h

SCORING SYSTEM: Draize (1944) and CIVO-grading system

Primary irritation to the skin is measured by a patch-test technique on the abraded and the intact skin of albino rabbits.
Twelve healthy adult New Zealand White albino rabbits were used for the test substance. 24 hours prior to applying the materials, the 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 g of the test substance was brought into contact of the intact and the 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 abraded skin. The abrasions are minor incisions through the stratum corneum, but not sufficiently deep to disturb the derma or to produce 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-). 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 CIVO-grading system.
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 h; 72h
Score:
ca. 0
Max. score:
0
Reversibility:
other: no irritation
Remarks on result:
other: Intact and abraded skin
Other effects:
No other effects

Table 2: Individual and average skin irritation scores of Bis(4-tert-butylcyclohexyl) peroxydicarbonate

Rabbit number

Intact skin

 

Abraded skin

24 hours

72 hours

Rabbit number

24 hours

72 hours

A

B

A

B

 

A

B

A

B

5516

0

0

0

0

5510

0

0

0

0

5517

0

0

0

0

5511

0

0

0

0

5518

0

0

0

0

5512

0

0

0

0

5519

0

0

0

0

5513

0

0

0

0

5520

0

0

0

0

5514

0

0

0

0

5521

0

0

0

0

5515

0

0

0

0

average

0

0

average

0

0

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Bis(4-tert-butylcyclohexyl) peroxydicarbonate did not cause any signs of skin irritation.
Executive summary:

In a primary dermal irritation study, 12 healthy adult New Zealand White albino rabbits were dermally exposed to 0.5 g of Perkadox 16 (Bis(4-tert-butylcyclohexyl) peroxydicarbonate) to an area of 1 inch² on abraded or intact skin of the back of 6 animals in each case. Test sites were covered with an occlusive dressing for 24 hours. Animals were then observed for 72 hours. Irritation was scored according the method of Draize et al. 1944 and the CIVO grading system. No reaction at all was observed. In this study Bis(4-tert-butylcyclohexyl) peroxydicarbonate is not a dermal irritant. 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: comparable to guideline study with acceptable restriction
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
: no clinical observation after 1 h; 6 animals were used
Qualifier:
according to
Guideline:
other: Fed. Reg. 28 (119), 5582, 1963 (published by the FDA of the USA) and Draize and Kelley (Drug. Cosmet. Industr. 71 (1952) 36)
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Housing: individually
- no hay or other extrageneous material that might enter the eye
- examination of the eyes before testing
Vehicle:
unchanged (no vehicle)
Controls:
other: The untreated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg
Duration of treatment / exposure:
Single treatment. The eyes were not washed after treatment. The exposure period is as long as observation period.
Observation period (in vivo):
Observation after 24 h, 48h, 72 h and 7 days after exposure.
Number of animals or in vitro replicates:
6 animals
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): no washing
SCORING SYSTEM: FDA scoring scale (see table 1)

TOOL USED TO ASSESS SCORE: binocular
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
other: 24 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
other: 48 h
Score:
ca. 0.83
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
other: 72 h
Score:
ca. 0.5
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 48 h

Table 1: Individual scores awarded in the ocular lesions elicited by bis(4-tert-butylcyclohexyl) peroxydicarbonate    

Rabbit number

Cornea

Iris

Conjunctivae

Redness

Chemosis

After 24 hours

1

0

0

1

1

2

0

0

> 1

1

3

0

0

1

1

4

0

0

1

1

5

0

0

> 1

1

6

0

0

1

1

After 48 hours

1

0

0

1

0

2

0

0

1

0

3

0

0

1

0

4

0

0

0

0

5

0

0

1

0

6

0

0

1

0

After 72 hours

1

0

0

1

0

2

0

0

0

0

3

0

0

1

0

4

0

0

0

0

5

0

0

1

0

6

0

0

0

0

After 7 days

1

0

0

0

0

2

0

0

0

0

3

0

0

0

0

4

0

0

0

0

5

0

0

0

0

6

0

0

0

0

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Bis(4-tert-butylcyclohexyl) peroxydicarbonate causes ocular lesions of slight degree. According the FDA-Standards it is not considered to be an eye irritant.
Executive summary:

In a primary eye irritation study 100 mg of bis(4-tert-butylcyclohexyl) peroxydicarbonate was instilled into the everted lower lid of one eye of 6 New Zealand White albino rabbits for 24 hours. The eyes were not washed after instillation. Animals were observed after 24, 48 and 72 hours and after 7 days. Irritation was scored with the FDA scoring scale. After 24 hours grade 1 of conjunctivae redness and chemosis was observed in all animals. Chemosis was reversible in all animals after 24 hours, redness diminished after seven days. As in terms of conjunctivae irritation scores score 1 is not considered as positive effect and because of the fully reversibility of the effect, bis(4-tert-butylcyclohexyl) peroxydicarbonate is not considered to be an eye irritant.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Primary irritation of the skin was measured by a patch-test technique on the abraded and the intact skin of 12 adult New Zealand White albino rabbits. After an exposure period of 24 hours the patches and the material applied were removed and the resulting skin reactions were evaluated by the method of Draize. A second reading was made 48 hours later (72 hours after application). Since the Draize grading system does not comprise abnormalities found in a second reading after 72 h these were carried out on the basis of the CIVO-grading system. The test material did not cause any signs of skin irritation, neither on the intact skin nor on the abraded skin. According to the Draize and CIVO-grading systems di-(4-tert-butylcyclohexyl) peroxydicarbonate is non-irritating to the skin of rabbits.

In an acute eye irritation study according to FDA-standards, 0.1 g of di-(4-tert-butylcyclohexyl)peroxydicarbonate was instilled into the eyes of six New Zealand White albino rabbits. Eyes were not washed after application. Animals then were observed after 24, 48, 72 hours and 7 days. Irritation was evaluated using the FDA scoring-scale. The test material caused slight redness and slight swelling of the conjunctivae in all rabbits. After 48 h the slight swelling of the chemosis was gone. The slight redness of the conjunctivae was reversible after 7 days. During the seven-day observation period the eye lesions recovered completely. Based on the results of this test and according to the FDA-standard the test material is not considered to be an eye irritant in rabbits.


Justification for selection of skin irritation / corrosion endpoint:
Comparable to guideline study with acceptable restrictions (key study).

Justification for selection of eye irritation endpoint:
Comparable to guideline study with acceptable restrictions (key study).

Justification for classification or non-classification

Di-(4-tert-butylcyclohexyl)peroxydicarbonate is not irritating/corrosive to the skin and not irritating to the eyes based on the results of appropriate studies.