Registration Dossier

Administrative data

Description of key information

Dicumyl peroxide was found to be not irritating to skin and eye.

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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study with full report
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Remarks:
Life Science Research Ltd
Test system:
other: in vivo testing
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Rosemead Rabbits, Rosemead, Waltham Abbey, Essex, England
- Age at study initiation: 3.5 to 4 months
- Weight at study initiation: 2.9 to 3.12 kg
- Housing: individually
- Diet: standard pelleted rabbit diet (SQC Rabbit Diet, Special Diets Services Ltd), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: not specified (based on infromation in report assumed to be more than a week)


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22°C
- Humidity (%): 45-56%
- Air changes (per hr): 15/h
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5g
Duration of treatment / exposure:
4 h
Observation period:
72 h
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 6x6 cm
- Type of wrap if used: unmedicated gauze (3x2cm), held in place on the left site by strips of blenderm; right site, acting as a control, was covered by a similar semi-occlusive dressing but otherwise remained untreated


REMOVAL OF TEST SUBSTANCE
- Washing (if done): warm water
- Time after start of exposure: after 4h


SCORING SYSTEM: according to Draize
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: mean 24, 48, 72h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 72h
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: mean 24, 48, 72h
Score:
0.1
Max. score:
3
Reversibility:
fully reversible within: 72h
Irritant / corrosive response data:
See table below.

 

 

 

 

Response

 

Time of observation

Rabbit No.

 

 

1

2

3

Erythema

 

 

 

 

 

1 h

0

1

1

 

24 h

0

1

1

 

48 h

0

1

0

 

72 h

0

0

0

Edema

 

 

 

 

 

1 h

0

0

0

 

24 h

0

1

0

 

48 h

0

0

0

 

72 h

0

0

0

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the result of the study the substance was not irritating when tested on rabbit skin.
Executive summary:

Very slight erythema was observed in 2 rabbits during the first 24h follwing bandage removal, continuing in 1 rabbit at the 48 h examination. Very slight oedema was evident at the one test site at the 24 h obersavtion. The test site of both these rabbits was overtly normal at the 72 h examination.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study with GLP
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
LPT Laboratory of Pharmacology and Toxicology GmbH
Species:
rabbit
Strain:
Himalayan
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: LPT breeding station Löhndorf, Germany
- Age at study initiation: 6.5-7.5 m
- Weight at study initiation: 2.4, 2.7, and 3.0 kg
- Housing: singly
- Diet (e.g. ad libitum): ssniff K-H V2333, ssniff Spezialdiäten GmbH, Soest; ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 20 d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20+-3°C
- Humidity (%): 30-70%
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg of mortared test iteminto one eye
Duration of treatment / exposure:
1 h
Observation period (in vivo):
1 d test, 72 h follow-up period
Number of animals or in vitro replicates:
3 (test was initially performed using 1 animal; as no corrosive or servere irritant effects were observed, 2 further animals were employed 24 after start of first initial test)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with 20mL 0.9% NaCl solution
- Time after start of exposure: 1h


SCORING SYSTEM: cornea: max. score 4, iris: max. score 2, conjunctivae: max. score 3, chemosis: max. score 4 (for specification of score see test report)


TOOL USED TO ASSESS SCORE: hand-slit lamp and fluorescein
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 72 h
Score:
0
Max. score:
13
Reversibility:
fully reversible
Irritant / corrosive response data:
Corneal opacity (grade 1) was observed in animal no. 3 twenty-four and fourty-eight hours after instillation
The fluorescein test performed twenty-four hours after instillation revealed corneal staining in animal no. 3 (up to 1/4 of the surface).
Conjunctival redness (grade 1) was observed in all animals 60 minutes , in animals nos. 2 and 3 until twenty-four hours after instillation.
The irises were not affected by instillation of the test item.
Other effects:
There were no systemic intolerance reactions.

Effects of 100 mg dicumylperoxide in right rabbit eye

 

Cornea

Iris

Conjunctivae

 

 

Opacity

 

Redness#

Chemosis##

 

 

animal no.: 1/2/3

 

 

Before dosing

0/0/0

0/0/0

0/0/0

0/0/0

60 min

0/0/0

0/0/0

1/1/1

0/0/0

24h

0/0/1

0/0/0

0/1/1

0/0/0

48h

0/0/1

0/0/0

0/0/0

0/0/0

72h

0/0/0

0/0/0

0/0/0

0/0/0

 

 

# refers to palpebral and bulbar conjunctivae; excluding cornea and iris

## swelling: refers to lids and/or nictating membrane

24 h fluorescein test: animal no. 3: corneal staining (up to 1/4 of the surface)

 

left eye: untreated control, all scores 0/0/0

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the result of the study the substance was not irritating when tested on rabbit eye.
Executive summary:

Dicumyl peroxide was tested at 100 mg in rabbit eye. The overall irriation score was 0 of max. 13 after 72 h. The effects observed after 24 and 48 h (all grade 1 for cornea opacity and conjunctivae redness) were fully reversible after 72h.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a study according to OECD guideline 404 dicumyl peroxide was found to be not irritating to skin based on EU criteria, when tested semi-occlusive on rabbit skin. Very slight erythema and oedema was observed in two and one animal after 24 h, respectively. No effects were observed after 72 h.

In a study according to OECD guideline 405 dicumyl peroxide was found to be not irritating to eye based on EU criteria, when tested in rabbit eyes.

Justification for classification or non-classification

Based on the results of reliable experimental studies classification of dicumyl peroxide as skin or eye irritant is not warranted based on EU regulation 1272/2008.