Registration Dossier

Administrative data

Description of key information

There are two rabbit skin irritation studies, one key study and one supporting study, both which demonstrate that dilauroyl peroxide does not meet the criteria for skin irritation.

There are two rabbit eye irritation studies, one key study and one supporting study, both which demonstrate that dilauroyl peroxide does not meet the criteria for eye irritation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

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: Apparently well conducted GLP study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
Not applicable
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: 362
Time point:
24/48/72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal: 362
Time point:
24/48/72 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal: 2091
Time point:
24/48/72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal: 2091
Time point:
24/48/72 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal: 455
Time point:
24 h
Score:
1
Irritation parameter:
erythema score
Basis:
animal: 455
Time point:
48 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal: 455
Time point:
72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal: 455
Time point:
24/48/72 h
Score:
0
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:
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:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

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:
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: Apparently well conducted study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues 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. A tray 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.
Vehicle:
unchanged (no vehicle)
Controls:
other: The untreated eye served as a control
Amount / concentration applied:
0.1 gram
Duration of treatment / exposure:
One instillation
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3
Details on study design:
Each rabbit was inspected on arrival and unsuitable individuals were rejected. Individual bodyweight was recorded for each animal on the day of
receipt 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. This record was consulted before an animal was allocated to study. Both eyes of each animal were examined before administration of the test material for signs of pre-existing irritation, reaction or abnormality which would prevent it from
being used on the study. Each cage was labelled with details of the schedule number, ear-tag number, sex, administration, treatment level,

Bodyweights on the day of dosing were within the range 3.04 - 4.52 kg. The rabbits were approximately either three or six months old at this time.

Each animal was gently restrained. The dose was instilled into the right eye by pulling the lower eye lid away from the eyeball to form a cup into
which 0.1 g of the test material was dropped. The eyelids were gently held together for one second and then released. The left eye remained
untreated.

The behaviour of each rabbit was observed for several minutes immediately following instillation of the test material to allow assessment of the initial pain response.

The animals were returned to their cages and checked at least twice during the first hour after dosing, at regular intervals throughout the day and
daily to ensure that the treated eye was not subject to infection or causing distress. Ocular reactions to treatment were assessed 1, 24, 48 and 72
hours after treatment. Reactions not included below were described in detail. Additional observations of persistent ocular lesions or irritation
responses were made seven days after treatment. The untreated eye was used as a comparison with the treated eye during assessment of ocular
lesions. An ophthalmoscope was used to facilitate inspection of the eyes.
Irritation parameter:
cornea opacity score
Remarks on result:
other: see table
Irritation parameter:
iris score
Remarks on result:
other: see table
Irritation parameter:
conjunctivae score
Remarks on result:
other: see table
Irritation parameter:
chemosis score
Remarks on result:
other: see table
Irritant / corrosive response data:
A diffuse crimson~red conjunctival appearance or injection of the conjunctival blood vessels was observed in all rabbits during the first 24 hours
following instillation, continuing in one animal to the 48 hour examination and in another up to the 72 hour examination. Very slight chemosis and
very slight or slight discharge were observed during the first 24 hours after treatment. The test eyes of two rabbits were overtly normal at the 72
hour examination; that of the remaining rabbit had recovered by the seventh day. Instillation of the test material caused practically no initial pain
response.
Other effects:
None

Summary of Ocular Lesions

Anim.

No.

Effect

Hours

Hours after application

Days after application

Mean

score cornea

24, 48, 72 hrs

Mean score iritis

24, 48, 72 hrs

Mean score redness 24, 48, 72 hrs.

Mean score chemosis 24, 48, 72 hrs.

1

24

48

72

4

7

1

Cornea

Iris

Redness

Chemosis

Discharge

Pain*

0

0

1

0

1

1

0

0

1

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0.3

0

2

Cornea

Iris

Redness

Chemosis

Discharge

Pain*

0

0

1

1

1

0

0

0

1

0

1

0

0

1

0

0

0

0

0

0

0

0

0

0.7

0

3

Cornea

Iris

Redness

Chemosis

Discharge

Pain*

0

0

2

1

2

1

0

0

2

0

0

0

0

1

0

0

0

0

1

1

0

0

0

0

0

0

0

0

1.3

0

*Evaluated upon instillation

Interpretation of results:
GHS criteria not met
Conclusions:
A diffuse crimson~red conjunctival appearance or injection of the conjunctival blood vessels was observed in all rabbits during the first 24 hours
following instillation, continuing in one animal to the 48 hour examination and in another up to the 72 hour examination. Very slight chemosis and
very slight or slight discharge were observed during the first 24 hours after treatment. The test eyes of two rabbits were overtly normal at the 72
hour examination; that of the remaining rabbit had recovered by the seventh day. Instillation of the test material caused practically no initial pain
response. According to GHS, Laurox is not classified as an eye irritant.
Executive summary:

Laurox was evaluated for potential eye irritation following the instillation of 0.1 gram into rabbit eyes In accordance with OECD 405. Response to pain was evaluated upon instillation. Ocular reactions were evaluated 1, 24, 48 and 72 hours and 7 days following instillation.

A diffuse crimson~red conjunctival appearance or injection of the conjunctival blood vessels was observed in all rabbits during the first 24 hours following instillation, continuing in one animal to the 48 hour examination and in another up to the 72 hour examination. Very slight chemosis and very slight or slight discharge were observed during the first 24 hours after treatment. The test eyes of two rabbits were overtly normal at the 72 hour examination; that of the remaining rabbit had recovered by the seventh day. Instillation of the test material caused practically no initial pain response.

According to GHS, Laurox is not classified as an eye irritant.

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

Additional information

Two rabbit skin irritation studies with dilauroyl peroxide are available, one an apparently well conducted GLP study conducted in accordance with OECD 404 (Rees, 1993) and one older less well documented study (Wazeter, 1973). Both demonstrate that dilauroyl peroxide should not be classified as a skin irritant following a 4 hour application.

Two rabbit eye irritation studies with dilauroyl peroxide are available, one an apparently well conducted GLP study conducted in accordance with OECD 405 (Rees, 1993) and one older less well documented study (Wazeter, 1973). Both demonstrate that dilauroyl peroxide should not be classified as an eye irritant.

Justification for classification or non-classification

Skin and eye irritation studies demonstrate that dilauroyl peroxide does not meet the criteria for classification.