Bisdecanoyl peroxide

Endpoint summary

Description of key information

In vivo skin irritation:

For this endpoint, a weight of evidence approach is used.

The acute dermal irritation of didecanoyl peroxide was evaluated in rabbits (Van Beek, 1979). This substance was applied to the skin of 6 New-Zealand white albino rabbits and held in contact for 24 hours by means of an occlusive dressing. There is no indication whether the substance was pre-moistened in water. The test was realised on intact and abraded skin. Scores over 24 and 72 hours for each animal were for erythema and for oedema. After application during 24 hours on the intact skin, didecanoyl peroxide induced a well-defined erythema and very slight edema and after 72 hours, a very slight to distinct scaliness. Therefore didecanoyl peroxide is considered as a moderate primary skin irritant when applied topically to rabbit skin under occlusive condition for 24 hours. Therefore, it can be reasonably considered as slightly irritating after a 4 -hour exposure like in an OECD 404 skin irritation test. This is supported by the absence of cutaneous reactions in rats following a 24-hour exposure to didecanoyl peroxide in the acute dermal toxicity study (Manciaux, 1998) and dilauryl peroxide, a very close substance, was shown not to be a skin irritant in a well conducted OECD 404 test (Rees, 1993).

In vivo eye irritation:

The potential of didecanoyl peroxide to induce ocular irritation was evaluated in 6 rabbits (Van Beek, 1979). A single dose of 100 mg of pure substance was instilled into the conjunctival sac. The other eye was not treated and served as control. The eyes were not rinsed after administration of the test item. Ocular reactions were observed approximately 24, 48, 72 hours and 7 days after the administration. Mean scores calculated over 24, 48 and 72 hours were 0 for cornea and iris, 0.67 for redness and 0.22 for chemosis of the conjunctivae. Otherwise all signs were fully reversible within 48 hours or 7 days.

Therefore, didecanoyl peroxide is not considered to be an eye irritant when administered by ocular route to 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:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Young albino rabbits of an outbred New Zealand White strain were supplied by Rosemead Rabbits, Rosemead, Waltham Abbey, Essex, England. They
were individually housed in suspended stainless steel cages mounted in mobile batteries (Modular Systems and Development Company limited,
London, England). The cages were fitted with perforated counter-sunk floor panels. Atray beneath the floor was lined with absorbent paper which was
changed regularly. Animals had free access to a commercially available standard pelleted rabbit diet (S.Q.C. Rabbit Diet, Special Diets Services
Limited, Witham, Essex, England). The rabbits had free access to tap water taken from the public supply; in England the supply and quality of this water is
governed by Department of the Environment regulations. Results of these analyses are retained in the archives. There was no information indicating
that normal levels of common contaminants, or specific contaminants, in the diet or drinking water would influence the outcome of the study.

The animals were housed in a lagomorph room within a limited-access building. The room was kept at slight positive pressure relative to the outside and had its own filtered air supply giving approximately 15 complete air changes per hour without re-circulation. A temperature range of 18-22°C
and a relative humidity range of 45-56% R.H. Electric time-switches operated a lighting cycle of 12 hours of artificial light per day. An emergency
generator was available to maintain the electricity supply in the event of a power failure.

Type of coverage:

semiocclusive

Preparation of test site:

other: Clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: Second untreated test site on each animal served as a control

Amount / concentration applied:

0.5 grams

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3

Details on study design:

Each animal was inspected on arrival, and unsuitable individuals were rejected. Individual bodyweight was recorded on the day of arrival and at weekly
intervals thereafter. All animals were identified by a uniquely numbered ear-tag. During the acclimatization period, the health status of each animal
was monitored and a record kept.

On the day before dosing, the dorsum between the limb girdles was clipped (chemical depilatories were not used). Bodyweight on the day of dosing was within the range 2.44 - 4.45 kg. The rabbits were either approximately three or six months old at this time.

Each rabbit was securely restrained by a technician. Two test sites (6 x 6 cm) were marked on either side of the clipped area of dorsum, moistened by direct application of approximately 0.2 ml distilled water per test site. A single dose (0.5 g) was applied directly to the skin and covered by an
unmedicated gauze patch (3 x 2 cm) which was held in place on the left test site by strips of Blenderm (Community Care Products, 3M Health Care,
Loughborough, England). The right test site, acting as a control, was covered by a similar semi-occlusive dressing but otherwise remained untreated. Pads of cotton wool and elasticated bandage were used to protect the patches and ensure good contact between the skin and the test material during the four-hour exposure period. The elasticated bandage was held in place by thin strips of waterproof plaster ('Blenderm') at both edges.
The dressings were removed after four hours exposure; the treatment sites were gently washed with warm water and dried with paper towels to
remove excess test material adhering to the skin.

Assessment of skin irritation responses at the control and treated test sites were made 1, 24, 48 and 72 hours after removal of the bandages.
Reactions of the test sites were assessed according to the criteria of Draize (1959) below .

Irritation parameter:

erythema score

Basis:

animal: #1 and 3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

edema score

Basis:

animal: #1, 2 and 3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Very slight erythema was observed in one rabbit during the first 24 hours following bandage removal. The test site of this rabbit was overtly normal by the 48 hour examination. No dermal response was observed at the test site of the remaining two animals at any time during the 72 hour
observation period.
The control sites did not show any response to the control procedure.

Other effects:

None

Summary of dermal lesions (following 4-h application)

no.	Effect	1  hour*	24-hours	48-hours	72-hours	Mean score erythema 24/48/72 h	Mean score oedema 24/48/72 h
362	Erythema/ eschar Oedema	0 0	0 0	0 0	0 0	0	0
455	Erythema/ eschar Oedema	1 0	1	0 0	0 0	0.3	0
2091	Erythema/ eschar Oedema	0 0	0	0 0	0 0	0	0

*~One hour following removal of dressing

Interpretation of results:

GHS criteria not met

Conclusions:

The 4 hour application of Laurox to the skin of rabbits, induced very slight erythema was observed in one rabbit during the first 24 hours following bandage removal. The test site of this rabbit was overtly normal by the 48 hour examination. No dermal response was observed at the test site of the remaining two animals at any time during the 72 hour observation period. Laurox is not classified as a skin irritatant in accordance with GHS.

Executive summary:

The irritation potential of Lauox was assessed following the 4 hour application of 0.5 grams to the skin or rabbits in accordance with OECD 404. Test sites were evaluated for irritation one hour following bandage removal and 24, 48 and 72 hours following application. The 4 hour application of Laurox to the skin of rabbits, induced very slight erythema was observed in one rabbit during the first 24 hours following bandage removal. The test site of this rabbit was overtly normal by the 48 hour examination. No dermal response was observed at the test site of the remaining two animals at any time during the 72 hour observation period. Laurox is not classified as a skin irritatant in accordance with GHS.

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:

1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

other: US Fed.Reg. 28 (119), 5582, 1963

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- caged individually

Vehicle:

not specified

Controls:

yes, concurrent no treatment

Amount / concentration applied:

100 mg

Duration of treatment / exposure:

No washed

Observation period (in vivo):

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

Number of animals or in vitro replicates:

6 rabbits

Details on study design:

SCORING SYSTEM: the FDA-scoring scale was used to grade the severity of eye reactions.

positive reactions were: opacity of the cornea, ulceration of the cornea, inflammation of the iris, slight circumcorneal injection or if such substances produce in the conjunctivae an obvious swelling with partial eversion of the lids, a diffuse deep-crimson red with individual vessels not easily discernable.

The test was considered positive if four or more of the animals in the test group of 6 rabbits exhibit a positive reaction.
If two or three animals exhibited a positive reaction, the test is repeated.

reading materials: binocular magnifying glass; diagnostic of corneal damages : 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.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.22

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Interpretation of results:

GHS criteria not met

Conclusions:

Didecanoyl peroxide was not considered to be eye irritant.

Executive summary:

The potential of didecanoyl peroxide to induce ocular irritation was evaluated in rabbits following a technique similar to OECD 405 guideline.

A single dose of 100 mg of pure substance was instilled into the conjunctival sac. The other eye was not treated and served as control. The eyes were not rinsed after administration of the test item.

Ocular reactions were observed approximately 24, 48, 72 hours and 7 days after the administration. The scores for chemosis, redness of the conjunctiva, iris lesions and corneal opacity were calculated for each animal.

Scores calculated for each animal over 24, 48 and 72 hours were 0 for cornea and iris, and 0 or 1 for redness and chemosis of the cunjonctivae. Otherwise all signs were fully reversible within 7 days.

Under these experimental conditions, didecanoyl peroxide was slightly irritating when administered by ocular route to rabbits.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

According to EU Regulation (EC) N0. 1272/2008 (CLP), the substance is not classified for skin or eye irritation.