Registration Dossier

Administrative data

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

Referenceopen allclose all

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.

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

Referenceopen allclose all

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 EU C&L.
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.

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

Additional information

Justification for classification or non-classification

Based on the available information the subsatnce is classified as irritating to the skin category 2 based on CLP criteria.