Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Based on the results obtained from testing the substance was considered as skin irritant but not as eye irritant. In addition respiratory irritation was observed after peak exposure in acute inhalation studies (see IUCLID section 7.2.2).

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:
1998-10-20 to 1998-11-10
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted 1992
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
1992
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Broekman Institute, Someren, The Netherlands
- Age at study initiation: 7-8 weeks old
- Weight at study initiation: 1260-1650 g
- Housing: individually housed in labelled cages with perforated floors
- Diet: standard laboratory rabbit diet; approx. 100 g per day
- Water: Free access to tap-waterdiluted with decalcified water.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 21 °C
- Humidity: 50 %
- 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:
1, 24, 48 and 72 hours and 7 and 14 days
Number of animals:
3 male rabbits
Details on study design:
TEST SITE
- Area of exposure: 6 square centimeters
- Type of wrap if used: Metalline patch

REMOVAL OF TEST SUBSTANCE
- Washing: The dressing was removed and the remaining test item removed using a tissue moistened with tap-water and subsequently a dry tissue.
- Time after start of exposure: 4 hours

SCORING SYSTEM: according to guidelines
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
no. 1379
Time point:
24/48/72 h
Score:
2.7
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
no.1383
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
no. 1384
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
no. 1379
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
no. 1383
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
no.1384
Time point:
24/48/72 h
Score:
2.7
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
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 well defined or moderate to 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 all animals. Reduced flexibility of the skin was present in one animal after 72 hours. Bald skin at the edges of the application-area and/or scaliness were observed among the animals between 7 and 14 days after exposure.

Corrosion:
There was no evidence of a corrosive effect o the skin.
Other effects:
Colouration:
No staining of the treated skin by the test item was observed.

Toxicity/Mortality:
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occured.
Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
In an in vivo skin irritation study with rabbits, TBPPI was shown to be irritating to the skin.
Executive summary:

Primary skin irritaton/corrosion study with tert-butyl peroxypivalate in rabbit (4 -hour semi-occlusive application) according to EU method B.4 and OECD guideline no. 404. Three rabbits were exposed to 0.5 mL of tert-butyl peroxypivalate, applied onto clipped skin for 4 hours using a semi-occlusive dressing. Obersations were made 1, 24, 48 and 72 hours and 7 and 14 days after exposure.


Exposure to tert-butyl peroxypivalate resulted in well defined or moderate to severe erythema and moderate or severe oedema in the treated skin-aeras of the three rabbits with mean erythema score of 2.3 and mean edema score of 2.7.


The skin irritation had resolved within 14 days after exposure in all animals. Reduced flexibility of the skin was present in one animal after 72 hours. Bald skin at the edges of the application-area and/or scaliness were observed among the animals between 7 and 14 days after exposure.


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 tert-butyl peroxypivalate to intact rabbit skin. Thus, the substance was evaluated to be skin irritating.

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:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Principles of method if other than guideline:
In general Draize scoring system and the regulations of the Federal Hazardous Substances Act are followed.
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Kuiper's Rabbit Ranch, Gary, Indiana
- Weight at study initiation: 2473 to 2787 g
- Housing: individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 15 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled conditions
- Humidity (%):controlled conditions
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
single treatment
Observation period (in vivo):
24, 48, 72 hours and 7 days
Number of animals or in vitro replicates:
3 females, 3 males
Details on study design:
REMOVAL OF TEST SUBSTANCE: no washing
SCORING SYSTEM: according to Draize system with further modifications: inclusion of 0.5 scores
TOOL USED TO ASSESS SCORE: fluorescein
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:
animal #1
Time point:
24/48/72 h
Score:
0.5
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0.16
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
3
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0.16
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.16
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0.16
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
other: discharge
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
3
Interpretation of results:
GHS criteria not met
Conclusions:
The test material TBPPI, is not irritating to the eyes as tested in rabbits.
Executive summary:

Three male and 3 female New Zealand White rabbits (obtained from Kuiper's Rabbit Ranch, Gary, Indiana) were used for this study. The rabbits weighed from 2473 to 2787 grams at the beginning of the study. The rabbits were individually housed in hanging wire-mesh cages in temperature and humidity controlled quarters. They were maintained in accordance with the recommendations contained in H.E.W. Publication No. 74-23 (N.I.H.) entitled "Guide for the Care and Use of Laboratory Animals". The animals were conditioned for a period of 15 days prior to study initiation. Water and Purina Rabbit Chow were available ad libitum. Prior to test material administration, the eyes of each rabbit were examined with ultraviolet light following instillation of one drop of a 2.0 percent sodium fluorescein solution. Rabbits exhibiting corneal lesions were discarded. The rabbits received 0.1 mL of the test material. The test material was placed into the cupped conjunctival sac of the right eye of each rabbit following which the eyelids were gently held together for one second. The left eye served as the untreated control for each rabbit. None of the rabbits received a washout. The treated eyes were examined in accordance with the following schedule: 24 hours following instillation, 48 hours, 72 hours and 7 days. After 72 hours and 7 days, sodium fluorescein examinations were conducted. After grading the eye reaction, one drop of sodium fluorescein was instilled directly onto the corneal surface of each rabbit. After few seconds, excess stain was flushed from the corneal surface with dis tilled water and the eyes examined with ultraviolet light. In 5 of 6 animals eyes weak redness and chemosis could be observed after 24 hours, which were reversible within 72 hours. Based upon the data obtained and in accordance with the requirements of the regulations of the Federal Hazardous Substances Act, the test material would not be considered a primary eye irritant.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation


Key study


Primary skin irritaton/corrosion study with tert-butyl peroxypivalate in rabbit (4 -hour semi-occlusive application) according to EU method B.4 and OECD guideline no. 404 is available. Three rabbits were exposed to 0.5 mL of tert-butyl peroxypivalate, applied onto clipped skin for 4 hours using a semi-occlusive dressing. Observations were made 1, 24, 48 and 72 hours and 7 and 14 days after exposure.


Exposure to tert-butyl peroxypivalate resulted in well defined or moderate to severe erythema and moderate or severe oedema in the treated skin-areas of the three rabbits with mean erythema score of 2.3 and mean edema score of 2.7. The skin irritation had resolved within 14 days after exposure in all animals.


Reduced flexibility of the skin was present in one animal after 72 hours. Bald skin at the edges of the application-area and/or scaliness were observed among the animals between 7 and 14 days after exposure.


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 occurred by dermal application of tert-butyl peroxypivalate to intact rabbit skin.


 


Supporting study (1976)


Primary irritation to the skin of tert-butyl peroxypivalate 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 are removed and resulting skin reactions were evaluated by method of Draize The mean erythema score of 2.5 and mean edema score of 0.6 was determined.


A second reading was made 48 hours later (72 hours after application).


Tert-butyl peroxypivalate caused well-defined erythema or some ischemia and very slight or slight edema. After 72 hours very slight erythema or scaliness were observed.


 


Supporting study (1978)


The study examined the skin irritation potential of t-butyl peroxypivalate (75 % in mineral spirit). 6 white rabbits (in which skin of 3 of them was abraded with a scalpel blade) were applied with 0.5 mL of the test substance for 24 hours and then washed with tap water The application sites were covered in an occlusive dressing. The skin was examined 24 and 72 hours after application. The test substance causing skin effefects. Primary skin irritation score of 2.3 was determined (the average of all the erythema scores plus the average of all the edema scores). According to the mean primary irritation score evaluation 2.3 is defined as mildly irritating.


 


Eye irritation


Key Study (1976)


Tert-butyl peroxypivalate 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. Thus, this test item is not considered to be eye irritant.


 


Supporting study (1978)


Three male and 3 female New Zealand White rabbits (obtained from Kuiper's Rabbit Ranch, Gary, Indiana) were used for this study. The rabbits weighed from 2473 to 2787 grams at the beginning of the study. The rabbits were individually housed in hanging wire-mesh cages in temperature and humidity controlled quarters. They were maintained in accordance with the recommendations contained in H.E.W. Publication No. 74-23 (N.I.H.) entitled "Guide for the Care and Use of Laboratory Animals". The animals were conditioned for a period of 15 days prior to study initiation. Water and Purina Rabbit Chow were available ad libitum. Prior to test material administration, the eyes of each rabbit were examined with ultraviolet light following instillation of one drop of a 2.0 percent sodium fluorescein solution. Rabbits exhibiting corneal lesions were discarded. The rabbits received 0.1 mL of the test material. The test material was placed into the cupped conjunctival sac of the right eye of each rabbit following which the eyelids were gently held together for one second. The left eye served as the untreated control for each rabbit. None of the rabbits received a washout. The treated eyes were examined in accordance with the following schedule:


24 hours following instillation, 48 hours, 72 hours and 7 days. After 72 hours and 7 days, sodium fluorescein examinations were conducted. After grading the eye reaction, one drop of sodium fluorescein was instilled directly onto the corneal surface of each rabbit. After few seconds, excess stain was flushed from the corneal surface with distilled water and the eyes examined with ultraviolet light. In 3 of 3 male and 2 of 3 female eyes weak redness and chemosis could be observed after 24 hours, which were reversible within 72 hours. Thus, the test material would not be considered a primary eye irritant.


 


Respiratory irritation- Acute toxicity inhalation studies (see IUCLID Section 7.2.2):


Tert-butyl peroxypivalate was tested in an acute inhalation toxicity study. Four groups of 5 male and 5 female rats were exposed to an aerosol atmosphere of tert-butyl peroxypivalate. The four "metered" concentrations were 17.1, 8.3, 4.2, 2.0 mg/L respectively. Slight to marked dyspnea and deaths were observed in all groups of rats at concentrations above 2.0 mg/L. Necropsy of the dead rats revealed reddened lungs with dark red patches and discoloration of the liver. The 4 hours LC50 was calculated to be 7.79 mg/L with 95 % confidence limits of 5.89 and 10.28 mg/L. Furthermore, an acute inhalation toxicity study, published by Gage J.C. (1970) is available. Tert- butyl peroxypivalate was irritant to the respiratory tract but no mortality was observed with a concentration of 200 ppm (corresponding to 1.45 mg/L).

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 for skin irritation Cat. 2 (H315: "Causes skin irritation) and STOT SE Cat. 3 (H335: "May cause respiratory irritation") according to Regulation (EC) No 1272/2008 (CLP), as amended for the eighteenth time in Regulation (EU) 2022/692.