Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Tert-Butylperoxy-3,5,5-trimethylhexanoat was tested for skin irritation/corrosion properties in two studies with rabbits. In the key study, tert-Butylperoxy-3,5,5-trimethylhexanoat was not irritating to skin according to EU method B.4 and OECD 404. In the supporting study tert-Butylperoxy-3,5,5-trimethylhexanoat revealed irritating effects under unrealistic stringed test conditions (24 h occlusive patch), which are not relevant for C&L deduction.
Tert-Butylperoxy-3,5,5-trimethylhexanoat was tested for eye irritation/corrosion in a study with rabbits. Tert-Butylperoxy-3,5,5-trimethylhexanoat is not considered to be eye irritant.

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:
2009-09-10 to 2010-01-07
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
The in vivo study was conducted under the purpose of another regulation.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH, D-88353 Kisslegg.
- Age at study initiation: approximately 9 weeks at the time of the administration
- Weight at study initiation: 2.1 kg
- Housing: individual caging in terulan cages
- Diet: ad libitum, Ssniff K-H maintenance diet for rabbits
- Water: ad libitum, tap water from an automatic watering system
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: average of about 20 °C
- Humidity: average of 30 - 70 %
- Photoperiod (hrs dark / hrs light): artificial light from 6 a.m. to 6 p.m.
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 hrs
Observation period:
1, 24, 48 and 72 hrs after patch removal
Number of animals:
3 females
Details on study design:
TEST SITE
- Area of exposure: dorsal area of the trunk
- Type of wrap if used: self adhesive non woven fabric, hypoallergenic
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritant / corrosive response data:
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.
Other effects:
2/3 animals gained weight in the week p.a. 1/3 animals gained no weight in the week p.a. All areas to be treated with the test substance and all control were normal before the application and at each observation time.
Interpretation of results:
GHS criteria not met
Conclusions:
According to Commission Directive 2001/59/EC tert-Butylperoxy-3,5,5-trimethylhexanoat does not require classification for skin irritation.
Executive summary:

Tert-Butylperoxy-3,5,5-trimethylhexanoat was tested to three rabbits in accordance with the OECD Guideline 404 and the Council (EC) No 440/2008, Method B.4.

0.5 mL tert-Butylperoxy-3,5,5-trimethylhexanoat was applied via a patch to a site of about 2.5 cm x 2.5 cm of the intact skin of each of 3 New Zealand White rabbits and covered by semi-occlusive dressing. The duration of the exposure was 4 hours.

First the test substance was administered to one animal. As no serious skin reactions were noted in this animal, the remaining two animals were exposed to the test substance one week later.

Body weights were investigated at the start and at the termination of the test. The animals were examined once daily for other than local changes of the skin. The treated areas of the animals were examined for erythema/eschar and oedema as well as for other local alterations (such as hyperplasia, scaling, discolouration, fissures, scabs and alopecia) approximately 1, 24, 48 and 72 hours after patch removal.

No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Erythema/Eschar: Not observed at any observation point.

Oedema: Not observed at any observation point.

The following mean scores were calculated for each animal from the examinations 24 h, 48 h and 72 h p.a.:

 

Mean Scores for Animal No.

 

41

42

43

Erythema/Eschar

0

0

0

Oedema

0

0

0

According to Commission Directive 2001/59/EC tert-Butylperoxy-3,5,5-trimethylhexanoat does not require classification for skin irritation.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: adult
- Housing: The animals are caged individually and receive no hay or other extraneous material that might enter the eyes.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: One tenth of a mL of the test substance is allowed to fall on the averted lower lid of one eye of each rabbit.
Duration of treatment / exposure:
one application
Observation period (in vivo):
24, 48, 72 hours and 7 days after installation of the test material
Number of animals or in vitro replicates:
6
Details on study design:
The eyes are not washed following installation and the animals are released immediately.

SCORING SYSTEM: The response is positive if, at any of the readings, discernable opacity of the cornea (other than a slight dulling of the normal lustre), or ulceration of the cornea, or inflammation of the iris (other than a deepening of the folds (rugae) or a slight circumcorneal injection), or if such substances produce in the conjunctivae (palpebral and bulbar, excluding the cornea and iris) an obvious swelling with partial reversion of the lids, or a diffuse deep-crimson red with individual vessels not easily discernable. The FDA-scoring scale was used. The test is considered positive if four or more of the animals in the test group of six rabbits exhibit a positive reaction. If one animal exhibits a positive reaction, the test is regarded as negative.

TOOL USED TO ASSESS SCORE: Ocular reactions are read using a binocular magnifying glass. The diagnosis of corneal damage is confirmed, if necessary, by staining the eyes of the animals with fluorescein-impregnated papers. After flushing the excess fluorescein solution, the eyes are examined in a dark room under ultraviolet illumination.
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:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Time point:
24/48/72 h
Score:
0.2
Max. score:
3
Reversibility:
fully reversible within: 72 hrs
Other effects:
The ocular effects Trigonox 42 S were as follows:
slight redness of the conjunctivae in one out of six rabbits

Individual scores awarded to the ocular lesions elicited by Trigonox 42 S:

rabbit

cornea

iris

conjunctivae

redness

chemosis

after 24 hours

9

0

0

1

0

10

0

0

0

0

11

0

0

0

0

12

0

0

0

0

13

0

0

0

0

14

0

0

0

0

after 48 hours

9

0

0

1

0

10

0

0

0

0

11

0

0

0

0

12

0

0

0

0

13

0

0

0

0

14

0

0

0

0

after 72 hours

9

0

0

0

0

10

0

0

0

0

11

0

0

0

0

12

0

0

0

0

13

0

0

0

0

14

0

0

0

0

Interpretation of results:
GHS criteria not met
Conclusions:
The present eye irritation test showed that, according to the FDA-standards, tert-Butylperoxy-3,5,5-trimethylhexanoat is not considered to be eye irritant.
Executive summary:

Tert-Butylperoxy-3,5,5-trimethylhexanoat was tested to six New Zealand White albino rabbits. In general the techniques of tests as published by the FDA of the United States (Fed. Reg. 28 (119), 5582, 1963) and Draize and Kelly (Drug Cosmet. Industr. 71 (1952) 36) for eye irritation test are followed.

Six New Zealand White albino rabbits are used. The animals are caged individually and receive no hay or other extraneous material that might enter the eyes. One tenth of a mL of the test substance is allowed to fall on the averted lower lid of one eye of each rabbit; the upper and lower eye lid is then carefully closed and subsequently held together for at least one second before releasing, to prevent loss of material. The other eye, remaining untreated, served as a control. The eyes are examined at 24, 48, 72 hours and 7 days after installation of the test material.

Tert-Butylperoxy-3,5,5-trimethylhexanoat caused minimal lesions in one out of six rabbits. The present eye irritation test showed that, according to the FDA-standards, tert-Butylperoxy-3,5,5-trimethylhexanoat is not considered to be eye irritant.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin


The test substance was tested for skin irritation/corrosion properties in two studies with rabbits. In the key study, the test substance was tested on rabbits according to EU method B.4 and OECD guideline 404. After a 72 h observation period, no irritation was observed with mean values of 0 for erythema score and for oedema score. Under the conditions of the study, the test substance was considered not irritating to skin.


In a supporting study the test substance revealed irritating effects under test conditions beyond conditions relevant for chemical hazard assessment (24 h occlusive patch). Therefore, this study results were not considered relevant for classification and labelling.


 


Eye


The test substance was tested for eye irritation/corrosion in rabbits. Based on the results obtained, mean values of 0 or for the parameters examined, the test substance was considered not irritating to eyes.


 


Respiratory tract


No indication of respiratory irritation from occupational use.

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 not classified for skin and eye irritation according to Regulation (EC) No 1272/2008 (CLP), as amended for the seventeenth time in Regulation (EU) 2021/849.