Registration Dossier

Administrative data

Description of key information

Based on the results from testing in vivo and in vitro the substance was considered as irritating to skin, but not irritating to the eye.

 

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
Study period:
1999-11-09 to 2000-01-04
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
1992
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1992
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River UK Limited, Margate, Kent, England
- Age at study initiation: at least 6 weeks
- Weight at study initiation: less than 3.5 kg
- Housing: individually housed in labelled cages with perforated floor
- Diet: standar laboratory rabbit diet approx. 100 g per day
- Water: free access to tap-water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 21 °C
- Humidity: 30-70 %
- Air changes: 15 air changes per hour
- Photoperiod: 12 hours artificial fluorescent light and 12 hours dark per day

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 mL

Duration of treatment / exposure:
4 hours
Observation period:
21 days
Number of animals:
3 animals of one sex
Details on study design:
TEST SITE
- Area of exposure: 2x3 cm
- Type of wrap if used: a metalline patch was mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing: the dressing was removed and the skin cleane of residual test substance using water
- Time after start of exposure: four hours

SCORING SYSTEM: according to guideline
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24,48,72 hours
Score:
2.7
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24, 48, 72 hours
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24, 48, 72 hours
Score:
2.7
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
2.8
Max. score:
4
Reversibility:
fully reversible within: 21 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24, 48, 72 hours
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24, 48, 72 hours
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24, 48, 72 hours
Score:
2.7
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
2.7
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritant / corrosive response data:
- Irritation:
Four hours exposure to 0.5 mL of the test item resulted in moderate to severe or severe erythema and moderate to severe oedema in the treated skin-areas of the three rabbits. The skin irritation had resolved within 14 days after exposure in one animal and within 21 days in the two remaining animals. Reduced flexibility and/or fissuring of the skin, scaliness and bald skin were noted among the animals between 48 hours and termination (after 14 or 21 days).

- Corrosion
There was no evidence of a corrosive effect on the skin.
Other effects:
- Colouration
On the skin of all animals, sticky remnants of the test substance were present on day 1 and dry remnants were present from day 2 onwards until day 4.

- Toxicity / Mortality
No symptoms of systemic toxicity were observed in the animals during the test period and no test substance related mortality occured.
Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
No evidence of full thickness destruction of the skin or scar tissue was observed during the observation period, indicating that no corrosion of the skin had occured by dermal application of the test substance to intact rabbit skin.
Executive summary:

Tert-butyl peroxyneodecanoate (75 % in solvent) was tested in a primary skin irritation/corrosion study in the rabbit (4 -hour semi-occlusive application) according to EU method B.4 and the OECD guideline no. 404. Three rabbits were exposed to 0.5 mL of the test item, applied onto clipped skin for 4 hours using a semi-occlusive dressing. Observations were made 1, 24, 48 and 72 hours and 7, 14 and/or 21 days after exposure.

Exposure to the test item resulted in moderate to severe erythema and moderate to severe oedema in the treated skin-areas of the three rabbits

with mean erythema score of 2.8 and mean edema score of 2.7. The skin irritation had resolved within 14 days after exposure in one animal and within 21 days in the two remaining animals. Reduced flexibility and/or fissuring of the skin, scaliness and bald skin were noted among the animals between 48 hours and termination (after 14 or 21 days). On the skin of all animals, sticky remnants of the test substance were present on day 1 and dry remnants were present from day 2 onwards until day 4.

No evidence of full thickness destruction of the skin or scar tissue was observed during the observation period, indicating that no corrosion of the skin had occured by dermal application of the test substance to intact rabbit skin.

Endpoint:
skin corrosion: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2011-10-05 to 2011-10-07
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EU Method B.40 (In Vitro Skin Corrosion: Transcutaneous Electrical Resistance Test (TER))
Version / remarks:
30 May 2008
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 431 (In Vitro Skin Corrosion: Reconstructed Human Epidermis (RHE) Test Method)
Version / remarks:
2004
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)
Version / remarks:
2009
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Version / remarks:
2010
Deviations:
no
GLP compliance:
yes
Test system:
human skin model
Source species:
other: not applicable
Cell type:
non-transformed keratinocytes
Justification for test system used:
The EpiDerm™ human skin model for distinguishing between corrosive and non-corrosive chemicals is recommended by the Regulation (EC) 440/2008: B.40.bis. and the OECD-Guideline 431.
The EpiDerm™ human skin model for distinguishing between skin irritating and non-irritating chemicals is recommended by the Regulation (EC) 761/2009: B.46 and the OECD-Guideline 439.
Vehicle:
unchanged (no vehicle)
Details on test system:
RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: MatTek's EpiDerm System
- Initial starting date: 2011-10-05

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: room temperature
- Temperature of post-treatment incubation: 37 °C

REMOVAL OF TEST MATERIAL AND CONTROLS
- Volume and number of washing steps: Tissues were gently rinsed with PBS (2 times)
- Modifications to validated SOP: none

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- Incubation time: 3 hours at 37 °C in an incubator with 5 % CO2
- Spectrophotometer: Plate spectrophotometer, Automated Microplate Reader EPOCH
- Wavelength: 570 nm
- Filter: without reference filter

NUMBER OF REPLICATE TISSUES: Skin Corrosivity Test: 2, Skin Irritation Test: 3

NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION: 1

PREDICTION MODEL / DECISION CRITERIA (choose relevant statement)
- A substance is classified "corrosive" in any case, if the relative tissue viability after 3 minutes treatment is below 50 %. In addition, those substances classified "non corrosive" after 3 minutes (viability > 50 %) are classified "corrosive" if the relative tissue viability after 1 hour treatment is below 15 %. The test substance is considered to be irritant if the mean relative tissue viability of three individual tissues exposed to the test substance is reduced below 50 % of the mean viability of the negative controls. In addition, those substances classified "non corrosive" after 3 minutes (viability > 50 %) are classified "corrosive" if the relative tissue viability after 1 hour treatment is below 15 %.
Control samples:
yes, concurrent negative control
yes, concurrent positive control
Amount/concentration applied:
TEST MATERIAL
- Amount(s) applied: 50 µL directly atop the EpiDerm tissue (Skin corrosion), 30 µL directly atop the EpiDerm tissue (Skin Irritation)
- Concentration: unchanged

Duration of treatment / exposure:
EpiDerm Skin Corrosivity Test:
- 3 minutes
- 1 hour

EpiDerm Skin Irritation Test:
- 1 hour
Duration of post-treatment incubation (if applicable):
Skin Irritation: 42 hours
Number of replicates:
2 (Skin corrosion)
3 (Skin irritation)
Details on test animals and environmental conditions:
not applicable
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
3 minutes (Skin corrosion test)
Value:
94.7
Vehicle controls validity:
not examined
Negative controls validity:
valid
Positive controls validity:
valid
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
1 hour (Skin corrosion test)
Value:
114.5
Vehicle controls validity:
not examined
Negative controls validity:
valid
Positive controls validity:
valid
Irritation / corrosion parameter:
% tissue viability
Run / experiment:
Skin Irritation
Value:
8.5
Vehicle controls validity:
not examined
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
positive indication of irritation
Other effects / acceptance of results:
ACCEPTANCE OF RESULTS:
a) EpiDerm Skin Corrosivity Test
- The mean OD of the tissues, treated with deionised water (negative control) was 2.112 after 3 minutes, and 1.906 after 1 hour of exposure, that is higher than 0.800, as required by the assay acceptance criteria.
- The mean tissue viability of the 1 hour positive control was 10.0 %, that is lower than 15.0 %, as required by the assay acceptance criteria.
- The coefficient of variation of the test item treated skin discs were 0.1 for the 3 minutes and 0.0 for the 1 hour exposure, that is below 0.3 as required by the assay acceptance criteria.
The method was acceptable as the concurrent positive and negative control and the coefficient of variation calculated from individual percental tissue viabilities fell within the acceptable ranges given by the protocol used during the ECVAM validation study.

b) EpiDerm Skin Irritation Test
- The mean OD of the tissues, treated with deionised water (negative control) was 2,003 , that is higher than 1.000 and lower than 2.500 as required by the assay acceptance criteria.
- The mean tissue viability of the positive control was 6.3 %, that is lower than 20.0 %, as required by the assay acceptance criteria.
- The standard deviation calculated from individual percental tissue viabilities of the test item treated skin discs was 3.3 %, that is below 18.0 % as required by the assay acceptance criteria.
The method was acceptable as the concurrent positive and negative control and the standard deviation calculated from individual percental tissue viabilities fell within the acceptable ranges given by the protocol used during the ECVAM validation study.
Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
According to the results of this study, the test substance is considered to be non-corrosive but irritant to skin.
Executive summary:

The in vitro EpiDerm Skin Corrosivity/Irritation Test was performed to reveal possible irreversible tissue damages of the skin following the application of TBPND according to EU (B.40 and B.46) and OECD guidelines (432 and 439).

EpiDerm Skin Irritation Test: The test substance was topically applied for 60 minutes to the epidermal surfaces of three-dimensional human epidermis models. After a post-incubation of 42 hours, a cell viability test was performed.

EpiDerm Skin Corrosivity Test: During the post-incubation of 42 hours the test substance was topically applied for 3 minutes and 1 hour to the epidermal surfaces of three-dimensional human epidermis models, followed by immediate determination of the cytotoxic effect.

Results

EpiDerm Skin Corrosivity Test:

- The mean percentage viability of the treated skin discs after 3 minutes of exposure was 94.7 % which is above the threshold of 50.0 % for classification.

- The mean percentage viability of the treated skin discs after 1 hour of exposure was 114.5 % which is above the threshold of 15.0 % for classification.

EpiDerm Skin Irritation Test:

- The mean percentage viability of the treated skin discs was 8.5 % which is above the threshold of 50.0 % for classification.

CONCLUSION

According to the results of this study, the test substance is considered to be non-corrosive but irritant to skin.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
In general the techniques of tests as published by FDA of the United States (Fed. Reg. 28 (119), 5582, 1963) and Draize and Kelley Drug Cosmet. Industr. 71 (1952) 36) are followed.
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Housing: individually


Vehicle:
unchanged (no vehicle)
Controls:
other: the other eye, remaining untreated , serves as a control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: one tenth of a milliliter of the test substance


Duration of treatment / exposure:
single treatment
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: the eyes are not washed following instillation


SCORING SYSTEM:
- Cornea:
No ulceration or opacity: 0
Scattered or diffuse areas of opacity (other than slight dulling of normal luster), details or iris clearly visible: (1)*
Easily discernible translucent areas, details of iris slightly obscured: 2
Nacrreous areas, no details of iris visible, size of pupil barely discernible: 3
Complete corneal opacity, iris not discernible: 4

- Iris:
Normal: 0
Markedly deepend folds, congestion, swelling, moderate circumcorneal injection (any of these or combination of any thereof), iris still reacting to light (sluggish reaction is positive): (1)*
No reaction to light, haemorrhage, gross detruction (any or all of these): 2

- Conjunctivae
1) Redness
Vessels normal: 0
Some vessels definitely injected: 1
Diffuse, crimson red, individual vessels not easily discernible: (2)*
Diffuse beefy red: 3

2) Chemosis
No swelling: 0
Any swelling above normal (includes nictitating membrane): 1
Obvious swelling with partial eversion of lids: (2)*
Swelling with lids about half closed: 3
Swelling with lids more than half closed: 4

* Bracket figures indicate lowest grades considered positive.

Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48 hours
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48 hours
Score:
0
Max. score:
2
Reversibility:
other: no effects
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48 hours
Score:
0.2
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48 hours
Score:
0
Max. score:
4
Reversibility:
other: no effects
Irritant / corrosive response data:
The eye lesions caused by the test item generally were of a slight degree. Thus, this test item is not considered to be eye irritant.
Interpretation of results:
GHS criteria not met
Conclusions:
The eye lesions caused by tert-butyl peroxyneodecanoate generally were of a slight degree. Thus, this test item is not considered to be eye irritant.
Executive summary:

Tert-butyl peroxyneodecanoate (75 % in solvent) was examined for eye irritating properties in six New Zealand White albino rabbits. One tenth of a milliliter of the test item is allowed to fall on the everted lower lid one eye of each rabbit; the upper and lower eye lid are then carefully closed and subsequently held together for at least one second before releasing, to prevent loss of material. The other eye, remaining untreated, serves as a control. The eyes are examined at 24, 48, 72 hours and 7 days after instillation of the test item.

The eye lesions caused by the test item generally were of a slight degree with mean cornea score of 0, iris score of 0, conjuctivae score 0.2 and chemosis score 0. Thus, the test substance was not considered to be an eye irritant.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
The test conducted in accordance with the regulations published in the Federal Register, Vol. 28, No. 110, pg 5582, June , 1963 and described in the Principles and Procedures for Evaluating and Toxicity of Household Substances, National Academy of Sciences, publication 1138.
In general the techniques of tests as published by FDA of the United States (Fed. Reg. 28 (119), 5582, 1963) and Draize and Kelley Drug Cosmet. Industr. 71 (1952) 36) are followed.
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Not indicated


Vehicle:
unchanged (no vehicle)
Controls:
other: the other eye, remaining untreated , served as a control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.1 mL test substance


Duration of treatment / exposure:
single exposure
Observation period (in vivo):
7 days (effects were examined at 24, 48, 72 hours and day 7)
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: the eyes were not washed after instillation


SCORING SYSTEM:
- Cornea:
No ulceration or opacity: 0
Scattered or diffuse areas of opacity (other than slight dulling of normal luster), details or iris clearly visible: (1)*
Easily discernible translucent areas, details of iris slightly obscured: 2
Nacrreous areas, no details of iris visible, size of pupil barely discernible: 3
Complete corneal opacity, iris not discernible: 4

- Iris:
Normal: 0
Markedly deepend folds, congestion, swelling, moderate circumcorneal injection (any of these or combination of any thereof), iris still reacting to light (sluggish reaction is positive): (1)*
No reaction to light, haemorrhage, gross detruction (any or all of these): 2

- Conjunctivae
1) Redness
Vessels normal: 0
Some vessels definitely injected: 1
Diffuse, crimson red, individual vessels not easily discernible: (2)*
Diffuse beefy red: 3

2) Chemosis
No swelling: 0
Any swelling above normal (includes nictitating membrane): 1
Obvious swelling with partial eversion of lids: (2)*
Swelling with lids about half closed: 3
Swelling with lids more than half closed: 4

* Bracket figures indicate lowest grades considered positive.

Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
, redness
Basis:
mean
Remarks:
animal 1
Time point:
other: 42, 48, 72 hours
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
, redness
Basis:
mean
Remarks:
animal 2
Time point:
other: 24, 48, 72 hours
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
, redness
Basis:
mean
Remarks:
animal 3
Time point:
other: 24, 48, 72 hours
Score:
0.66
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
, redness
Basis:
mean
Remarks:
animal 4
Time point:
other: 24, 48, 72 hours
Score:
1
Max. score:
3
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
, redness
Basis:
mean
Remarks:
animal 5
Time point:
other: 24, 48, 72 hours
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
, redness
Basis:
mean
Remarks:
animal 6
Time point:
other: 24, 48, 72 hours
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal 1
Time point:
other: 24, 48, 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal 2
Time point:
other: 24, 48, 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal 3
Time point:
other: 24, 48, 72 hours
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal 4
Time point:
other: 24, 48, 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal 5
Time point:
other: 24, 48, 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal 6
Time point:
other: 24, 48, 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days

Results of the sodium fluorescein (detect corneal lesions) were normal.

Interpretation of results:
GHS criteria not met
Conclusions:
The test substance was not considered as an eye irritant.
Executive summary:

Tert-butyl peroxyneodecanoate (75 % in solvent) was examined for eye irritating properties in six New Zealand White albino rabbits. 0.1 mL of the test item was applied to one eye of each rabbit while the other eye, remaining untreated, served as a control. The eyes were examined at 24, 48, 72 hours and 7 days after instillation of the test item. Mean cornea score and mean iris score of 0, mean conjunctivea score and mean chemosis score of 0.94 were determined. Based on the obtained results the test substance was not considered to be an eye irritant.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

skin irritation / corrosion

key study (in vivo)

Tert-butyl peroxyneodecanoate (75 % in solvent) was tested in a primary skin irritation/corrosion study in the rabbit (4 -hour semi-occlusive application) according to EU method B.4 and the OECD guideline no. 404. Three rabbits were exposed to 0.5 mL of the test item, applied onto clipped skin for 4 hours using a semi-occlusive dressing. Observations were made 1, 24, 48 and 72 hours and 7, 14 and/or 21 days after exposure.

Exposure to the test item resulted in moderate to severe erythema and moderate to severe oedema in the treated skin-areas of the three rabbits with mean erythema score of 2.8 and mean edema score of 2.7.

The skin irritation had resolved within 14 days after exposure in one animal and within 21 days in the two remaining animals. Reduced flexibility and/or fissuring of the skin, scaliness and bald skin were noted among the animals between 48 hours and termination (after 14 or 21 days).

On the skin of all animals, sticky remnants of the test substance were present on day 1 and dry remnants were present from day 2 onwards until day 4.

No evidence of full thickness destruction of the skin or scar tissue was observed during the observation period, indicating that no corrosion of the skin had occured by dermal application of the test substance to intact rabbit skin.

Supporting study (in vivo)

Primary irritation to the skin of tert-butyl peroxyneodecanoate (75 % in solvent) was measured by a patch-test technique on the abraded and intact skin of albino rabbits.

After an exposure period of 24 hours the patches and the material applied were removed and the resulting skin reactions were evaluted by the method of Draize. A second reading was made 48 hours later (72 hours after application).

The test item caused well-defined erythema or moderate to severe erythema or some ischemia and very slight or slight edema (mean erythema score 3.1 and mean edema score 1.1). After 72 hours very slight or well-defined erythema or scaliness were observed.

key study (in vitro)

In order to confirm the results of the two in vivo studies with the 75% substance in solvent an in vitro skin irritation/corrotion test was done with the pure subtance. This in vitro EpiDerm Skin Corrosivity/Irritation Test was performed to reveal possible irreversible tissue damages of the skin following the application of TBPND according to EU (B.40 and B.46) and OECD guidelines (432 and 439).

EpiDerm Skin Irritation Test: The test substance was topically applied for 60 minutes to the epidermal surfaces of three-dimensional human epidermis models. After a post-incubation of 42 hours, a cell viability test was performed.

EpiDerm Skin Corrosivity Test: During the post-incubation of 42 hours the test substance was topically applied for 3 minutes and 1 hour to the epidermal surfaces of three-dimensional human epidermis models, followed by immediate determination of the cytotoxic effect.

Results

EpiDerm Skin Corrosivity Test:

- The mean percentage viability of the treated skin discs after 3 minutes of exposure was 94.7 % which is above the threshold of 50.0 % for classification.

- The mean percentage viability of the treated skin discs after 1 hour of exposure was 114.5 % which is above the threshold of 15.0 % for classification.

EpiDerm Skin Irritation Test:

- The mean percentage viability of the treated skin discs was 8.5 % which is above the threshold of 50.0 % for classification.

CONCLUSION

According to the results of this study, the test substance is considered to be non-corrosive but irritant to skin confirming the results of the in vivo studies with the 75% substance.

Based on the results of the in vivo and in vitro studies Tert-butyl peroxyneodecanoate was considered irritating to skin.

Eye irritation

Tert-butyl peroxyneodecanoate (75 % in solvent) was examined for eye irritating properties in two studies. In both studies six New Zealand White albino rabbits were administered with 0.1 mL of the test item, applied to one eye of each rabbit while the other eye, remaining untreated, served as a control. The eyes were examined at 24, 48, 72 hours and 7 days after instillation of the test substance. Based on the obtained results (mean cornea score (0 in both studies), iris score (0 in both studies), conjuctivae score (0.2 in key study and 0.94 in supporting study) and chemosis score (0 in key study and 0.94 in supporting study)), the test substance was not considered to be an eye irritant.

No data are available for the pure (100%) test substance. Neverthesess, due to animal welfare reasons no further testing was conducted as the same result as for the 75% product is expected. The mean scores in the key study (cornea = 0, iris = 0, conjunctiviae = 0.2 and chemosis = 0) were very low. In addition, for skin irritation comparable results were obtained in an older in vivo study with the 75% substance as compared with a new in vitro skin irritation study with the pure (100%) substance. Taking all data together, it is expected that also the 100% substance is not irritating to the eyes.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data the test item is classified and labelled as skin irritating cat. 2 (H315: "Causes skin irritation") according to Regulation (EC) No 1272/2008 (CLP), as amended for the tenth time in Regulation (EU) No 2017/776.

Based on available data the test item is not classified and labelled as eye irritating according to Regulation (EC) No 1272/2008 (CLP), as amended for the tenth time in Regulation (EU) No 2017/776.