Registration Dossier

Administrative data

Description of key information

GLP guideline studies according to OECD 404 and OECD 405.

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:
1995-08-01 to 1995-08-21
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elevage Cunicole de Val de Selle, 80160 Prouzel, France
- Weight at study initiation: 2.4 kg +/- 0.2 kg
- Housing: individually
- Diet (e.g. ad libitum): free access
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 +/- 3°C
- Humidity (%): 30-70%
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light):12/12

Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Remarks:
the substance was used in original form (75.8% in hydrocarbon)
Controls:
other: untreated skin served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml of the test substance in active material corresponding to 0.66 ml in the finished product
- Concentration (if solution): 75.8 % in hydrocarbon
Duration of treatment / exposure:
The test substance was applied in a first assay for a period of 3 min and 4 h in one male New Zealand white rabbit. Since the substance was not strongly irritating in the first assay, it was applied for 4 h in a second assay.
Observation period:
The observation period was extended to a maximum of 14 days (until day 15) in order to determine the progress of lesions and their reversibility.
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 6 cm^2
- Type of wrap if used: dry gauze pad

REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiped of with moistened (4 h exposure) or dry (3 min exposure) gauze pad
- Time after start of exposure: 3 min or 4 h

SCORING SYSTEM: scoring scale 0-4 see table 1 in "any other information on materials and methods"
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 3 min
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 11 days
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 4 h
Score:
>= 0 - <= 2
Max. score:
2
Reversibility:
fully reversible within: 11 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 4 h
Score:
>= 0 - <= 2
Max. score:
2
Reversibility:
fully reversible within: 6 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 4 h
Score:
>= 0 - <= 2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 4 h
Score:
>= 0 - <= 2
Max. score:
2
Reversibility:
fully reversible within: 48 h
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 4 h
Score:
>= 0 - <= 4
Max. score:
4
Reversibility:
fully reversible within: 5 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 4 h
Score:
>= 0 - <= 2
Max. score:
2
Reversibility:
fully reversible within: 5 days
Other effects:
dryness of the skin observed in all animals latest on day 5 after 4 h exposure and on day 7 after 3 min exposure

Table 2: Mean irritant response data after 4 h exposure at day 2, 3 and 4

Rabbit number

Dermal Irritation

Mean irritation score (#)

Interpretation

1

Erythema

1.3

(-)

Oedema

0.7

(-)

Other

Dryness of skin from day 7 onwards

 

2

Erythema

2.0

(+)

Oedema

3.3

(+)

Other

Dryness of skin from day 5 onwards

 

3

Erythema

2.0

(+)

Oedema

2.0

(+)

Other

Dryness of skin from day 5 onwards

 

(#) mean irritation score on days 2, 3 and 4

(+) = irritant according to E.E.C. criteria

(-) = non-irritant according to E.E.C. criteria

 

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the experimental conditions, the test substance Di-(2-Ethylhexyl)-peroxycarbonate was considered irritant in rabbits. All effects were reversible.
Executive summary:

In a primary dermal irritation study according to the OECD guideline 404, 3 male rabbits (New Zealand white; 2.4 +/-0.2 kg) were dermally exposed to 0.5 ml of Di-(2-Ethylhexyl)-peroxydicarbonate (undiluted test material; 75.8 % in hydrocarbon) which corresponds to 0.66 ml in the finished product. The test sites were covered with a semi-occlusive dressing for 3 minutes and 4 hours, respectively. Animals were then observed for 14 days until day 15. The mean values of the scores for erythema and oedema were calculated for each animal.

After 3 minutes exposure very slight erythema (grade 1) was observed up to day 7; dryness of the skin was noted from day 7 onwards, masking evaluation of the erythema up to day 10.

After 4 hours of exposure very slight or slight erythema (grade 1 or 2) was observed up to days 4, 6 or 7. Slight or severe oedema (grade 2 and 4) was noted for 24 h in one animal, and up to day 4 in another animal. In the remaining rabbit, slight oedema was noted from days 2 to 4.

Dryness of the skin was observed from day 5 (two rabbits) or 7 to days 11, 13 or 15. It masked evaluation of erythema in one rabbit on day 5 and in animal on days 8 to 10.

Mean scores over 24, 48 and 72 hours for individual animals were 1.3, 2.0 and 2.0 for erythema and 0.7, 3.3 and 2.0 for edema.

In this study, Di-(2-Ethylhexyl)-peroxydicarbonate is a dermal irritant to the skin.

 

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (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: reversibiltiy of effects have not been tested
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
: reversibility after 21 days was not examined, no individual animal data
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: 1858 to 2447 g
- Housing: individually
- Diet (e.g. ad libitum): free access
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): maintained throughout study
- Humidity (%): maintained throughout study
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): undiluted
Duration of treatment / exposure:
Instilled into the conjunctival sac of the right eye in each rabbit. Exposure throughout the observation period.
Observation period (in vivo):
Observation after 24 h, 48 h and 72 h
Number of animals or in vitro replicates:
6 (3 males and 3 females)
Details on study design:
SCORING SYSTEM: Scale for scoring ocular lesions (Draize, J.H., 1959)
TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24 h
Score:
0
Max. score:
0
Remarks on result:
other: no data of individual animals
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24 h
Score:
0
Max. score:
0
Remarks on result:
other: no data of individual animals
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24 h
Score:
14.6
Reversibility:
not specified
Remarks on result:
other: no data of individual animals
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 48
Score:
0
Remarks on result:
other: no data of individual animals
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 48 h
Score:
0
Remarks on result:
other: no data of individual animals
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 48
Score:
13.6
Reversibility:
not specified
Remarks on result:
other: no data of individual animals
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 72 h
Score:
0
Remarks on result:
other: no data of individual animals
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 72 h
Score:
0
Remarks on result:
other: no data of individual animals
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 72 h
Score:
13
Reversibility:
not specified
Remarks on result:
other: no data of individual animals
Irritation parameter:
other: Conjunctivae Redness
Basis:
mean
Time point:
other: 24
Score:
>= 2 - <= 2.5
Max. score:
2.5
Reversibility:
not specified
Remarks on result:
other: no data of individual animals
Irritation parameter:
other: Conjunctivae Redness
Basis:
mean
Time point:
other: 48
Score:
>= 1 - <= 2.5
Max. score:
2.5
Reversibility:
not specified
Remarks on result:
other: no data of individual animals
Irritation parameter:
other: Conjunctivae Redness
Time point:
other: 72 h
Score:
>= 1 - <= 3
Max. score:
3
Reversibility:
not specified
Remarks on result:
other: no data of individual animals
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24 h
Score:
>= 3 - <= 4
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: no data on individual animals
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 48 h
Score:
>= 3 - <= 4
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: no data on individual animals
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 72 h
Score:
>= 3 - <= 4
Max. score:
4
Reversibility:
not specified
Remarks on result:
other: no data on individual animals
Irritation parameter:
other: Conjunctivae Discharge
Basis:
mean
Time point:
other: 24 h
Score:
>= 0.5 - <= 2.5
Max. score:
2.5
Reversibility:
not specified
Remarks on result:
other: no data on individual animals
Irritation parameter:
other: Conjunctivae Discharge
Basis:
mean
Time point:
other: 48 h
Score:
>= 0.5 - <= 2
Max. score:
2
Reversibility:
not specified
Remarks on result:
other: no data on individual animals
Irritation parameter:
other: Conjunctivae Discharge
Basis:
mean
Time point:
other: 72 h
Score:
>= 0.5 - <= 2
Max. score:
2
Reversibility:
not specified
Remarks on result:
other: no data on individual animals
Irritant / corrosive response data:
- varying degrees of conjunctival irritation in each animal at each observation level
- slight to marked redness, moderate to marked chemosis, very slight to moderate discharge
- no corneal damage

Table 1: Eye irritiation in the rabbit caused by Lupersol 223 (Di-(2-Ethylhexyl)Peroxydicarbonate)

Ocular area

Eye irritation in the rabbit

Observation period and average score (range)

24h

48h

72 h

Cornea

A

0

0

0

B

0

0

0

Cornea score

 

0

0

0

Iris

A

0

0

0

Iris score

 

0

0

0

Conjunctivae

A

2.2

(2.0-2.5)

2.1  (1.0-2.5)

1.8       (1.0-3.0)

B

3.8

(3.0-4.0)

3.6  (3.0-4.0)

3.7 (3.0-4.0)

C

1.3 (0.5-2.5)

1.1  (0.5-2.0)

1.0  (0.5-2.0)

Conjunctivae score

 

14.6

13.6

13.0

Total score

 

14.6

13.6

13.0

A: Redness

B: Chemosis

C: Discharge

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results Lupersol 223 would be considered an eye irritant.
Executive summary:

Lupersol 223 (Di-(Ethylhexyl)Peroxydicarbonate) was tested in 3 male and 3 female rabbits (New Zealand white) for eye irritation. An amount of 0.1 ml of the test substance was instilled into the conjunctival sac of the right eye of each rabbit. The eyes were not washed. Examinations were made after 24, 48 and 72 h and scored according Draize et al. 1959. Varying degrees of conjunctival irritation were observed in each test animal at each observation interval. These findings included slight to marked redness, moderate to marked chemosis and very slight to moderate discharge. Examination of the treated eyes at 72 h with UV light and sodium fluorescein did not reveal corneal damage. Adverse effects were observed but the observation period was not extended to 21 days to exclude a chronic effect. No data of the individually tested animals are provided but the average score. In this study Lupersol 223 (Di-(Ethylhexyl)Peroxydicarbonate) is an eye irritant.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation was tested in a GLP guideline study (CIT, 1995) according to OECD 404. Irritation scores were in the range of 1.3 to 2.0 (erythema) and 0.7 to 3.3 (oedema). All effects were reversible. The findings did not contradict an older study (CIVO, 1983) that was performed similar to OECD 404. The substance used in the latter study was not characterised sufficiently to rate the study as reliable.

Eye irritation: The test item produced effects on the conjunctiva in 2 of 3 tested animals. Reversibility was not examined. The effects did not show a clear decrease within 3 consecutive days. Thus, it cannot be concluded that the effects would be reversible within 21 days. The test item did not fulfil the alternative criteria scoring corneal opacity ≥ 3 and/or — iritis > 1,5. However, according to regulation 1272/2008 irreversible effects lead to classification as Category 1 (Irreversible effects on the eye). Thus Cat 1 is warranted based on missing data on the reversibility of the effect.

Justification for selection of skin irritation / corrosion endpoint:
key study

Justification for selection of eye irritation endpoint:
key study

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: irritating

Justification for classification or non-classification

Skin irritation was tested according to OECD 404. Irritation scores were in the range of 1.3 to 2.0 (erythema) and 0.7 to 3.3 (oedema). Only one of 3 animals had edema scores above 2.0. All effects were reversible. According to CLP this would be considered a borderline case and no classification would be warranted. Due to the slightly more severe irritation scores reported in the second, less reliable study (using a poor defined substance) the current classification (Skin Irrit Cat 2) was maintained.

Eye irritation was tested according to OECD 405. The test item produced effects on the conjunctiva in 2 of 3 tested animals. Reversibility of these effects was not examined. Two animals showed a slow decrease in the irritation score between the 24 and 96 h readings. The third animal did not show a decrease in the effect level within 3 consecutive days. Thus it was not possible to conclude a reversibility of the effects within 21 days. The test item did not fulfil the alternative criteria scoring corneal opacity ≥ 3.0 and/or — iritis > 1.5. Thus the justification for classification as Category 1 (irreversible effects on the eye) is weak and based only on the missing proof of reversible effects on the conjunctiva.