Registration Dossier

Administrative data

Description of key information

In an in vivo skin irritation test in rabbits (OECD 404, GLP), 3-hydroxy-1,1-dimethylbutylperoxy-neodecanoate was irritating for skin (Clouzeau, 1992c). In an in vivo eye irritation test in rabbits (OECD 405, GLP), the substance was not irritating for eyes.

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: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: New-Zealand albino
- Sex: male
- Source: Elevage Cunicole de Val de Selle (80160 Prouzel, France)
- Age: no data
- Weight at study initiation: 2.4 ± 0.1 kg
- Controls: auto-control (left flank)
-Upon their arrivai at C.I.T., the animals were acclimatized to the experimental environment for at least 5 days during which they were observed daily.
-They were individually identified with metallic ear-tags.

ENVIRONMENTAL CONDITIONS
- Temperature : 22 ± 3°C
- Humidity : 50 ± 20% relative humidity
- Light/dark cycle: 12 hours of light/12 hours of dark
- The air was non-recycled and filtered by absolute filters.
- Food and water: ad libitum
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: none
Controls:
other: The left flank did not receive any substance and served as a control.
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 mL:
- Concentration : undiluted
Duration of treatment / exposure:
4 hour(s)
Observation period:
The cutaneous reactions were evaluated one hour then 24, 48 and 72 hours after removal of the semi-occlusive dressing and then daily until day 15.
Number of animals:
3
Details on study design:
- Area of exposure: right flank, 6 cm2
- Total quantity applied: 0.5 ml
- Administration frequency: once
- Removal of test substance: no
EXAMINATIONS:
- Scoring system: Draize's score
- Examination time points: 1h, 24 h, 48 h and 72 hours after the patch removal.
Irritation parameter:
erythema score
Basis:
animal: 1 and 2
Time point:
other: 24, 48 and 72 hours
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 10 days
Remarks on result:
other: Desquamation up to d15
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
2.7
Max. score:
4
Reversibility:
fully reversible within: 9 days
Remarks on result:
other: Desquamation up to d15
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 6 days
Irritation parameter:
edema score
Basis:
animal: 2 and 3
Time point:
other: 24, 48 and 72 hours
Score:
2.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
A marked skin inflammation (erythema: mean scores of 2.7 to 3.0 and oedema: mean scores of 2.0 to 2.7) was observed during at least 72 hours. Reversibility of the oedema was recorded on day 7 and erythema was no longer observed on day 10. Between days 7 and 15, desquamation of the skin, signs of superficial reversible damages of the skin were observed in the 3 animals

 No residual test substance was observed after removal of the dressing.

Mean calculated score for each site

Observation period (hours) 

1       24      48        72   

Erythema   3,0     3,0     3,0       2,7 

Oedema        3,0     3,0     2,7       1,7   

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Remarks:
Migrated information
Executive summary:

The skin irritation potential of 3-hydroxy-1,1-dimethylbutylperoxy-neodecanoate was assessed in a skin irritation test conducted according to the OECD 404 guideline (GLP study)

A single dose of 0.5 ml of the test substance in its original form was prepared on a dry compress then applied to a 6 cm2 clipped areas of 3 male New Zealand White rabbits. The test substance was held in contact with the skin for 4 hours by means of a semi-occlusive dressing. The cutaneous reactions were observed one hour, 24, 48 and 72 hours after removal of the dressing and then daily until day 15. No residual test substance was observed after removal of the dressing. The mean score of the scores recorded after 24, 48 and 72 hours for each animal was calculated.

A marked skin inflammation (erythema: mean scores of 2.7 to 3.0 and oedema: mean scores of 2.0 to 2.7) was observed during at least 72 hours. Reversibility of the oedema was recorded on day 7 and erythema was no longer observed on day 10. Between days 7 and 15, desquamation of the skin, signs of superficial reversible damages of the skin were observed in the 3 animals. In conclusion the test substance was considered as irritant when administered by cutaneous route in rabbits.
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:
1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Sex: male
- Source: Elevage Cunicole de Val de Selle (80160 Prouzel, France)
- Age: no data
- Weight at study initiation: 2.6 ± 0.1 kg
- Controls: untreated right eye

ENVIRONMENTAL CONDITIONS
- Temperature : 20 ± 3°C
- Humidity : 50 ± 20% relative humidity
- Light/dark cycle: 12 hours of light/12 hours of dark
- The air was non-recycled and filtered by absolute filters.
- Food and water: ad libidum
- The animals were individually housed in polystyrene cages
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
- A single dose of 0.1 ml of the undiluted test substance in its original form was instilled into the conjunctival sac of the left eye of 3 animais after gently pulling the lower lid away from the eyeball. The lower and upper eyelids were held together for several seconds to avoid any loss of the test substance. The right eye, which remained untreated, served as a control.
- The eyes were not rinsed after administration of the test substance.
Observation period (in vivo):
4 days
Number of animals or in vitro replicates:
3
Details on study design:
EXAMINATIONS:
- Ophthalmoscopic examination: Yes
- Scoring system: Draize's scale
- Observation period: 1h, 24h, 48h and 72h after administration of the test substance
- Tool used to assess score: fluorescein:
To determine the presence or absence of corneal opacification and to evaluate the affected area, one or 2 drops of sodium fluorescein 0.5% solution can be instilled in the eye (however this must be performed after a period of 24 hours). If corneal opacification is difficult to determine, the eye can be examined under a U.V. lamp (a clear fluorescence is visible in the areas of opacification).
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
3
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritant / corrosive response data:
Slight (score of 1) conjonctival (chemosis, redness) reactions were observed in all animals one hour after instillation. No occular reactions remained after 24, 48 and 72 hours.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
Under the experimental conditions, the substance was not irritating to eyes in rabbits.
Executive summary:

The eye irritation potential of the substance was assessed in an in vivo test (OECD 405, GLP). Having confirmed that the test substance had an irritant effect when administered by cutaneous route, the study began with one animal. Then, the results were confirmed with 2 additional animais. A single dose of 0.1 ml of the test substance in its original form was instilled into the conjunctival sac of the left eye of 3 male New Zealand White rabbits. The eyes were not rinsed after instillation of the test substance. The ocular reactions were observed one hour, 24, 48 and 72 hours after the instillation. The mean score of the scores recorded after 24, 48 and 72 hours for each animal was calculated. Slight (score of 1) conjonctival (chemosis, redness) reactions were observed in all animals one hour after instillation. No ocular reactions remained after 24, 48 and 72 hours. Therefore the test substance is considered as ion-irritant when administered by ocular route in rabbits.

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

Additional information

The skin irritation potential of 3-hydroxy-1,1-dimethylbutylperoxy-neodecanoate was assessed in an in vivo skin irritation test conducted according to the OECD 404 guideline (Clouzeau, 1992). A marked skin inflammation (erythema: mean scores - after 24, 48 and 72 hours - of 2.7 to 3.0 and oedema: mean scores of 2.0 to 2.7) was observed during at least 72 hours. Reversibility of the oedema was recorded on day 7 and erythema was no longer observed on day 10. Between days 7 and 15, desquamation of the skin, signs of superficial reversible damages of the skin were observed in the 3 animals.Therefore the substance is considered as irritant when administered by cutaneous route in rabbits.

The eye irritation potential of the substance was assessed in an in vivo test (OECD 405). Having confirmed that the test substance had an irritant effect when administered by cutaneous route, the study began with one animal. Then, the results were confirmed with 2 additional animals. A single dose of 0.1 ml of the test substance in its original form was instilled into the conjunctival sac of the left eye of 3 male New Zealand White rabbits. The eyes were not rinsed after instillation of the test substance. The ocular reactions were observed one hour, 24, 48 and 72 hours after the instillation. The mean score of the scores recorded after 24, 48 and 72 hours for each animal was calculated. Slight (score of 1) conjunctival (chemosis, redness) reactions were observed in all animals one hour after instillation. No ocular reactions remained after 24, 48 and 72 hours. Therefore the substance is considered as non-irritant when administered by ocular route in rabbits.

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

Justification for classification or non-classification

According to EU Regulation (EC) N0. 1272/2008 (CLP), the substance is classified as a skin irritant (Category 2) but not as an eye irritant.