Registration Dossier

Administrative data

Description of key information

Tert.-Butylperoxy- 2-ethylhexanoat was tested in a skin irritation/corrosion properties in studies with rabbits. The test item showed slight signs of irritation on skin and very slight signs of irritation in eyes, which were fully reversible. It is concluded that tert.-Butylperoxy- 2-ethylhexanoat can be regarded as non irritant to eyes and to reveal slight skin irritative effects.

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Remarks:
No Guideline stated, no GLP statement available, more stringent test conditions as requires in OECD guidelines
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
more stringed test conditions
Principles of method if other than guideline:
NA
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
Source: Kuiper's Rabbit Ranch, Gary, Indiana
Housing: rabbits were individually housed in hanging wire-mesh cages in temperature and humidity controlled quarters
Conditioning period: 6 days prior to study initiation
Diet: ad libitum
Water: ad libitum
Body weights prior to administration: 2010 to 2770 g
Type of coverage:
occlusive
Preparation of test site:
other: 3 animals clipped and 3 animals abraded
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 mL


Duration of treatment / exposure:
24 hrs
Observation period:
24 and 72 hrs after application
Number of animals:
6 (3 male, 3 female)
Details on study design:
TEST SITE
- Area of exposure: back of each rabbit
- % coverage: 20 - 30 % of the body surface
- Type of wrap if used: the application sites were covered with gauze bandaging and overwrapped with Saran Wrap. The entire application area was then wrapped with several layers of 75 mm Elastoplast tape. A collar was also applied.


REMOVAL OF TEST SUBSTANCE
- Washing: the sites were washed with tepid tap water
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
33229/M
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
no data
Remarks on result:
other: intact skin
Remarks:
48 h were not assessed
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
33198/F
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
no data
Remarks on result:
other: intact skin
Remarks:
48 h were not assessed
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
33216/F
Time point:
24/48/72 h
Score:
1.5
Max. score:
4
Reversibility:
no data
Remarks on result:
other: intact skin
Remarks:
48 h were not assessed
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
1.8
Max. score:
4
Reversibility:
no data
Remarks on result:
other: intact skin
Remarks:
48 h were not assessed
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
33229/M
Time point:
24/48/72 h
Score:
1.5
Max. score:
4
Reversibility:
no data
Remarks on result:
other: intact skin
Remarks:
48 h were not assessed
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
33198/F
Time point:
24/48/72 h
Score:
1.5
Max. score:
4
Reversibility:
no data
Remarks on result:
other: intact skin
Remarks:
48 h were not assessed
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
33216/F
Time point:
24/48/72 h
Score:
0.5
Max. score:
4
Reversibility:
no data
Remarks on result:
other: intact skin
Remarks:
48 h were not assessed
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
1.2
Max. score:
4
Reversibility:
no data
Remarks on result:
other: intact skin
Remarks:
48 h were not assessed
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
33197/M
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
no data
Remarks on result:
other: abraded skin
Remarks:
48 h were not assessed
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
33225/M
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
no data
Remarks on result:
other: abraded skin
Remarks:
48 h were not assessed
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
33192/F
Time point:
24/48/72 h
Score:
1.75
Max. score:
4
Reversibility:
no data
Remarks on result:
other: abraded skin
Remarks:
48 h were not assessed
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
1.9
Max. score:
4
Reversibility:
no data
Remarks on result:
other: abraded skin
Remarks:
48 h were not assessed
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
33197/M
Time point:
24/48/72 h
Score:
1.5
Max. score:
4
Reversibility:
no data
Remarks on result:
other: abraded skin
Remarks:
48 h were not assessed
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
33225/M
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
no data
Remarks on result:
other: abraded skin
Remarks:
48 h were not assessed
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
33192/F
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
no data
Remarks on result:
other: abraded skin
Remarks:
48 h were not assessed
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
1.25
Max. score:
4
Reversibility:
no data
Remarks on result:
other: abraded skin
Remarks:
48 h were not assessed
Irritant / corrosive response data:
NA
Other effects:
NA

No remarks

Interpretation of results:
GHS criteria not met
Conclusions:
Following study results and the OECD GHS (1272/2008) criteria, tert.-Butylperoxy- 2-ethylhexanoat is not considered as an primary skin irritant. With regard to Commission Directive 67/548 the results represents a borderline case.
Executive summary:

Tert.-Butylperoxy- 2-ethylhexanoat was tested to three male and 3 female New Zealand White rabbits similar to OECD guideline 404 (but more stringed test conditions). The hair was removed from the back of each rabbit. (20 - 30 % of the body surface) with an electric clipper. The skin of 3 of the rabbits was abraded with a scalpel blade. The abrasion penetrated the stratum corneum, but were not deep enough to cause bleeding.

A volume of 0.5 mL of the test material was applied to the back of each rabbit under a one inch square gauze patch. The application sites were covered with gauze bandaging and overwrapped with Saran Wrap. The entire application area was then wrapped with several layers of 75 mm Elastoplast tape. A collar was also applied. Following 24 hours of application, the bandages and collars were removed and the sites were washed with tepid tap water and examined for skin irritation. The examinations were repeated at 72 hours.

The table below presents the grade of effect with time.

 

 

Intact skin

Abraded Skin

Observations

Value

24 hrs

72 hrs

24 hrs

72 hrs

Erythema, Eschar Formation

0

 

 

1/3

1/3

1

1/3

1/3

1/3

 

2

2/3

2/3

1/3

2/3

3

 

 

 

 

4

 

 

 

 

Oedema Formation

0

1/3

 

1/3

1/3

1

2/3

1/3

2/3

1/3

2

 

2/3

 

1/3

3

 

 

 

 

4

 

 

 

 

Calculation for Primary Skin Irritation Score (Score = The average of all the erythma scores plus the average of all the oedema scores): (18.5 ÷ 12) + (12 ÷ 12) = 2.5.

In this study, the test conditions were more stringed as required in OECD guidelines and can thus be regarded as worst case scenario.

The conditions in this study were 24 hours occlusive treatment, whereas in the OECD guideline 4 hours semi-occlusive treatment is requested.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not 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:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Principles of method if other than guideline:
NA
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
Source: H.A.R.E. Rabbits for Research, Hewitt, New Jersey
Housing: rabbits were individually housed in hanging wire-mesh cages in temperature and humidity controlled quarters
Conditioning period: 21 days prior to study initiation
Diet: ad libitum
Water: ad libitum
Body weights prior to administration: 2257 to 2817 g
Vehicle:
unchanged (no vehicle)
Controls:
other: left eye served as the untreated control
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 mL

Duration of treatment / exposure:
one application
Observation period (in vivo):
24, 48, 72 hrs, 7 days
Number of animals or in vitro replicates:
6 (3 male, 3 female)
Details on study design:
REMOVAL OF TEST SUBSTANCE
None of the rabbits received a washout


TOOL USED TO ASSESS SCORE: After grading the eye reaction, one drop of sodium fluorescein (at 72 hrs, 7 days) was instilled directly onto the corneal surface of each rabbit. After a few seconds, excess stain was flushed from the corneal surface with distilled water and the eyes examined with ultraviolet light.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #1
Remarks:
32829/M
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #2
Remarks:
32841/M
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 48 hrs
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #3
Remarks:
32843/M
Time point:
24/48/72 h
Score:
0.5
Max. score:
3
Reversibility:
fully reversible within: 48 hrs
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #4
Remarks:
32732/F
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 48 hrs
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #5
Remarks:
32834/F
Time point:
24/48/72 h
Score:
0.5
Max. score:
3
Reversibility:
fully reversible within: 72 hrs
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #6
Remarks:
32840/F
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 48 hrs
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Time point:
24/48/72 h
Score:
0.8
Max. score:
3
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Remarks:
(chemosis)
Basis:
animal #1
Remarks:
32829/M
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
32841/M
Time point:
24/48/72 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 48 hrs
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
32843/M
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
animal #4
Remarks:
32732/F
Time point:
24/48/72 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 48 hrs
Irritation parameter:
chemosis score
Basis:
animal #5
Remarks:
32834/F
Time point:
24/48/72 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 72 hrs
Irritation parameter:
chemosis score
Basis:
animal #6
Remarks:
32840/F
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 48 hrs
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0.4
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
3
Reversibility:
fully reversible
Other effects:
NA

No remarks

Interpretation of results:
GHS criteria not met
Conclusions:
Based upon the data obtained and in accordance with OECD GHS (1272/2008) the test material is evaluated as not irritating to eyes.
Executive summary:

Tert.-Butylperoxy- 2-ethylhexanoat was tested in three male and 3 female New Zealand White rabbits similar to OECD guideline 405. Prior to test material administration, the eyes of each rabbit were examined with ultraviolet light following instillation of one drop of a 2 % sodium 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. The treated eyes were examined in accordance with the following schedule: 24 hrs following instillation, 48 hrs, 72 hrs and 7 days. After grading the eye reaction, one drop of sodium fluorescein (at 72 hrs, 7 days) was instilled directly onto the corneal surface of each rabbit. After a few seconds, excess stain was flushed from the corneal surface with distilled water and the eyes examined with ultraviolet light. Based on the data obtained and in accordance with OECD GHS (1272/2008) 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:
no study available

Additional information

Skin:

In the key study, tert.-Butylperoxy- 2-ethylhexanoate was tested on three male and 3 female New Zealand white rabbits similar to OECD guideline 404 (occlusive test conditions).

The hair was removed from back of each rabbit with an electric clipper. The skin of 3 of the rabbits was abraded with a scalpel blade. A total of 0.5 mL of tert.-Butylperoxy- 2-ethylhexanoate was applied to back of each rabbit. The area of application was then wrapped with a gauze bandage (semi occlusive dressing). Four hours later the bandages were removed and the area was washed with tepid tap water and examined for skin irritation in accordance with the scale. These examinations were repeated at 24 and 72 hours. Based upon the results obtained, tert.-Butylperoxy- 2-ethylhexanoate was not considered a primary skin irritant nor a corrosive substance.

In the supporting study, tert.-Butylperoxy- 2-ethylhexanoate was tested in a skin irritation test in New Zealand White rabbits with the substance applied for 24 h under occlusive test conditions (similar to OECD guideline 404, but more stringed).

After a 72 h observation period, slight irritation was observed with mean values of 1.8 (intact skin) and 1.9 (abraded skin) for erythema and 1.2 (intact skin) and 1.25 (abraded skin) for oedema. As in the key study, tert.-Butylperoxy- 2-ethylhexanoate was considered not irritating.

Eye:

In the key study, tert.-Butylperoxy- 2-ethylhexanoate was tested for acute ocular irritation and reversibility in rabbits similar to OECD guideline 405.

The test item showed slight signs of irritation which were fully reversible. Thus, under the conditions of applied test, tert.-Butylperoxy- 2-ethylhexanoate was regarded as not irritant to eyes. Comparable results were obtained in the supporting study.


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 on skin and eye irritation, the test item does not require classification according to Regulation (EC) No 1272/2008 (CLP), as amended for the tenth time in Regulation (EU) No 2017/776.