Bis(α,α-dimethylbenzyl) peroxide

Endpoint summary

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:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system 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
- 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): 0.5 g

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:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.6

Max. score:

4

Reversibility:

fully reversible within: 72h

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

See table below.

Table 1: Skin irritation scores according to Draize

				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:

GHS criteria not met

Conclusions:

Based on the result of the study, the substance was not irritating when tested on rabbit skin.

Executive summary:

In a primary dermal irritation study (OECD guideline 404), three male New Zealand white rabbits were dermally exposed to 0.5 mg of the test item for 4 hours to a body surface area of 6 cm² under semi-occlusive conditions. Animals then were observed for 1, 24, 48 and 72 hours after removal of the dressings and test substance. The test item did not cause any skin effects, except very slight erythema observed in two rabbits during the first 24 h following bandage removal, continuing in one rabbit after 48 hours. Very slight oedema was evident at one test site at the 24 h observation. The test site of both these rabbits was overtly normal at the 72-h examination. Based on the results, the test item is considered to be non-irritating.

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:

2009-12-10 to 2010-02-25

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

24 April 2002

Deviations:

no

GLP compliance:

yes (incl. QA statement)

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 months
- Weight at study initiation: 2.4, 2.7, and 3.0 kg
- Housing: single
- 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:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.6

Max. score:

4

Reversibility:

fully reversible within: 72 h

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 h

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

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.

Table 1: Effects of 100 mg dicumylperoxide in the 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

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

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the result of the study the substance was not irritating when tested on rabbit eye.

Executive summary:

In a primary eye irritation study (OECD 405), 0.1 g of the test item was instilled into the conjunctival sac of one eye of each of three young adult Himalayan rabbits. Animals were observed for 14 days. Irritation was scored by the method of Draize. The behaviour and physical state of the rabbits, and the body-weight evolution were normal throughout the study. Only very mild conjunctival and corneal opacity reactions were observed, which were fully reversible within 72 hours. Based on the results, the test item can be considered as not irritating.

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.