tert-pentyl peroxypivalate

Endpoint summary

Description of key information

The test substance is severely irritating in an in vivo skin irritation study. A second study performed similarly does not show these effects. However, as a conservative approach the worst case study is chosen as the basis for classification. The test substance is a very mild eye irritant and based on the two available studies the criteria for classification are not met. An acute inhalation study performed at 9.5 g/m³ (aerosols, whole body) did not result in any signs of respiratory irritation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June 1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

None provided

Type of coverage:

occlusive

Preparation of test site:

other: intact and abraded

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 ml

Duration of treatment / exposure:

24 hours

Observation period:

72 hours

Number of animals:

six

Details on study design:

Primary irritation to the skin is measured by patch test technique on the abraded and intact skin of albino rabbits. Twelve healthy adult New Zealand White albino rabbits were used. Twenty four hours prior to applying the material the hair is removed from the backs of the animals with an electric clipper in such away as to avoid abrasion.
An amount of 0.5 mL (in case of liquids) or 0.5 g (in case of solids or semi-solids) of the test substance is brought on the intact or abraded skin under a surgical patch measuring 1 inch x 1 inch; The patches are fixed to the application site by means of adhesive tape and the entire trunk of the rabbits is wrapped with an impervious material to maintain the test patches in position and to retard evaporation of volatile substances.

Six rabbits are treated on the intact skin, the other six on the abraded skin. The abrasions are minor incisions through the stratum corneum but not sufficiently deep to disturb the derma or to produce bleeding.

After an exposure period of 24 hours the patches and the material applied are removed and the resulting skin reactions are evaluated by the method of Draize (J. Pharmacol. 82 (1944) 377 - 390). A second reading is made 48 hours later (72 hour after application).

Irritation parameter:

edema score

Basis:

animal: all animals

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritation parameter:

erythema score

Basis:

animal: all animals

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritation parameter:

erythema score

Basis:

mean

Time point:

24 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 72 hours

Remarks:

No further observations were made

Remarks on result:

positive indication of irritation

Irritation parameter:

erythema score

Basis:

mean

Time point:

72 h

Score:

3.33

Max. score:

4

Reversibility:

not fully reversible within: 72 hours

Remarks:

No further observations were made

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 72 hours

Remarks:

No further observatiosn were made

Remarks on result:

positive indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

72 h

Score:

0.5

Max. score:

4

Reversibility:

not fully reversible within: 72 hours

Remarks:

No further observations were made

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

The test product caused severe skin irritation.
The dermal effects after 24 hours generally consisted of ischemia and slight or moderate edema.
After 72 hours distinct scaliness was noted at two intact sites, while the other sites by then showed ischemia, slight or distinct incrustation and/or very slight edema.
In general, the reactions of the abraded skin were slightly more pronounced than those of the intact skin.

CLP criteria:

1) Mean value of ≥ 2,3 - ≤ 4,0 for erythema/ eschar or for oedema in at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after patch removal or, if reactions are delayed, from grades on 3 consecutive days after the onset of skin reactions; or

(2) Inflammation that persists to the end of the observation period normally 14 days in at least 2 animals, particularly taking into account alopecia (limited area), hyperkeratosis, hyperplasia, and scaling; or

(3) In some cases where there is pronounced variability of response among animals, with very definite positive effects related to chemical exposure in a single animal but less than the criteria above.

 

The summary below is based on the observation made in the animals with intact skin after 24 hours of occlusive exposure:

 

Erythema

Animal/score at:	24h	72h	mean
7	4	2	3
8	4	4	4
9	4	4	4
10	4	2	3
11	4	4	4
12	4	4	4

 

Oedema

Animal/score at:	24h	72h	mean
7	1	0	0.5
8	2	0	1
9	3	1	2
10	2	1	1.5
11	2	1	1.5
12	2	0	1

 

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

On the basis of the present results it is concluded that tert-amyl peroxypivalate is a severe primary skin irritant and is classified in category.

Executive summary:

The test article was evaluated for potential skin irritation following application to the intact and abraded skin of rabbits. The test sites were evaluated 24 hours following application and again 48 hours later according to the Draize method.

The test product caused severe skin irritation.

The dermal effects after 24 hours generally  consisted of ischemia and slight or moderate edema.

After 72 hours distinct scaliness was noted at two intact sites, while the other sites by then showed ischemia, slight or distinct incrustation and/or very slight edema.

In general, the reactions of the abraded skin were slightly more pronounced than those of the intact skin.

Reference 2

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

None provided

Controls:

no

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

One time instillation

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

Six

Details on study design:

In general the techniques of tests as published by the FDA of the United States (Fed, Reg, 28 (119), 5582, 1963) and Draize and Kelley (Drug Cosmet. Industr. 11 (1952) 36) are followed, Six New Zealand White albino rabbits are used for each test substance. The animals are caged individually and receive no hay or other extraneous material that might enter the eyes. The eyes of the animals are examined before testing and only those animals without observable eye defects are used. One tenth of a milliliter of the test substance, or in case of solids or semisolids, 100 milligrams of the test substance, is allowed to fall on the everted lower lid of 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 not washed following instillation and the animals are released immediately.
The eyes are examined at 24, 48, 72 hours and 7 days after instillation of the test material. An animal is considered as giving a positive reaction if there is, at any of the readings, discernible 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 slight 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 eversion of the lids, or a diffuse deep-crimson red with individual vessels not easily discernible. The FDA-scoring scale is 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. If two or three animals exhibit a positive reaction, the test is repeated, using a different group of six animals. The second test is considered as positive if three or more of the animals exhibit a positive reaction. If only one or two animals in the second test exhibit a positive reaction, the test is again repeated with a different group of six animals. Should a third test be needed the substance will be regarded as an irritant if two or more animals exhibit a positive response. A substance which has elicited corneal and/or iris lesions which have not cleared by the seventh day reading, is considered a severe eye irritant.

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.6

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Irritant / corrosive response data:

Tert-amyl peroxypivalate caused slight redness and/or swelling of the conjunctivae in all animals. After seven days eye irritation was no longer noticeable.

See attached table.

A substance is considered irritating to the eye acoording to CLP when:

If, when applied to the eye of an animal, a substance produces:

- at least in 2 of 3 tested animals, a positive response of:

- corneal opacity ≥ 1 and/or

- iritis ≥ 1, and/or

- conjunctival redness ≥ 2 and/or

- conjunctival oedema (chemosis) ≥ 2

- calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material, and which fully reverses within an observation period of 21 days

 

Conjunctivae /score at:	24h	48h	72h
Redness	1	0.5	0.33
Chemosis	0.5	0.16	0.16

* average score (range)

 

Score of 0 for Cornea and Iris.

 

All effects were fully reversible within 7 days.

Interpretation of results:

GHS criteria not met

Conclusions:

On the basis of the results obtained it is concluded that, according to the FDA-standards, tert-ainylperoxypivalate is not considered to be an eye irritant.

It is not classified as an eye irritatiant in accordance with Regulation (EC) No 1272/2008, as amended for the 17th time in Regulation (EU) 2021/849.

Executive summary:

The test article was evaluated for its eye irritation potential following instillation of 0.1 mL into rabbit eyes. The test article caused slight redness and/or swelling of the conjunctivae in all animals After seven days eye irritation was no longer noticeable. Therefore, the test article is not classified as an eye irritant.

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the results of an in vivo skin irritation study the test substance has to be classified as irritating to skin Category 2 according to Regulation (EC) No 1272/2008, as amended for the 17th time in Regulation (EU) 2021/849.

 

On the basis of the results obtained from an eye irritation in vivo study it is concluded that, tert-amylperoxypivalate is not classified as an eye irritatiant in accordance with Regulation (EC) No 1272/2008, as amended for the 17th time in Regulation (EU) 2021/849.