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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin 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:
other: Study performed according to established principles and published methods which were current at the time but not OECD guideline. There is no CoA for the test material; it is described only by trade name, lot number and physical appearance.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report date:
1982

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
see below
Principles of method if other than guideline:
- Exposure period was 24 hours under occlusion, not 4 hours under semi-occlusion.
- The protocol states that animals may be used for 1 - 4 test substances, although it cannot be determined whether or not that occurred in this study.
- The observation period was 72 hours not 14 days.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Di-tert-butyl 1,1,4,4-tetramethyltetramethylene diperoxide
EC Number:
201-128-1
EC Name:
Di-tert-butyl 1,1,4,4-tetramethyltetramethylene diperoxide
Cas Number:
78-63-7
Molecular formula:
C16H34O4
IUPAC Name:
2,5-bis(tert-butylperoxy)-2,5-dimethylhexane
Details on test material:
The test material was a clear colourless liquid, batch no. 220981.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Twelve health adult New Zealand White albino rabbits are used for 1-4 substances.

Test system

Type of coverage:
occlusive
Preparation of test site:
other: one part shaved only, one part shaved and abraded
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
24 hours
Observation period:
72 hours following patch removal
Number of animals:
Twelve (six intact, six abraded)
Details on study design:
Twenty four hours prior to applying the materials, the hair is removed from the backs of the animals with an electric clipper in such a way as to avoid abrasions. 0.5 ml 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. A second reading is made 48 hours later (72 hours after application).

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 hours
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: an additional 48 hours
Remarks on result:
other: intact skin; all scores 4 out of 4
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 hours
Score:
4
Max. score:
4
Reversibility:
other: last observation for this study
Remarks on result:
other: intact skin; all scores 4 out of 4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 hours
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: an additional 48 hours
Remarks on result:
other: intact skin; all scores 2 out of 4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 hours
Score:
1
Max. score:
1
Reversibility:
other: last observation for this study
Remarks on result:
other: intact skin; all scores 1 out of 4
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 hours
Score:
3.6
Max. score:
4
Reversibility:
not fully reversible within: an additional 48 hours
Remarks on result:
other: abraded skin; for erythema five animals had score 4 out of 4, one animals had score 2 out of 4
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 hours
Score:
3.5
Max. score:
4
Reversibility:
other: last observation for this study
Remarks on result:
other: abraded skin; five animals had score 4 out of 4, one animal had score 1 out of 4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 hours
Score:
1.3
Max. score:
2
Reversibility:
not fully reversible within: an additional 48 hours
Remarks on result:
other: abraded skin; two animals had score 2 out of 4, four animals had score 1 out of 4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 hours
Score:
0.7
Max. score:
1
Reversibility:
other: last observation for this study
Remarks on result:
other: abraded skin; four animals had score 1 out of 4, two animals had score 0 out of 4
Irritant / corrosive response data:
On the basis of the present results it can be concluded that the substance is a severe primary skin irritant.
Other effects:
None reported.

Any other information on results incl. tables

Its dermal effects observed after 24 hours generaly consisted of well-defined erythema, slight to distinct ischemia and very slight to slight edema. The dermal effects observed after 72 hours generally consisted of slight to distinct incrustation and very slight edema. There were no distinct differences between skin reactions of the intact skin and those of the abraded skin.

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
On the basis of the present results it can be concluded that the substance is a severe primary skin irritant. Mean value of > 2.3 - < 4.0 for erythema in all animals from gradings at 24, 48 and 72 hours after patch removal. Reversibilty of these effects cannot be judged from this study since the observations stopped after 72 hours. However corrosion was not observed and the animals were exposed for 24 hours instead of 4 hours.

Based on these results, the test substance needs to be labelled for skin irritation Cat 2 according to
the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the
United Nations (2017) (including all amendments) and Regulation (EC) No 1272/2008 on
classification, labelling and packaging of items and mixtures (including all amendments).
Executive summary:

Primary irritation to the skin is measured by a patch-test technique on the abraded and intact skin of albino rabbits. It caused severe skin irritation. Its dermal effects observed after 24 hours generaly consisted of well-defined erythema, slight to distinct ischemia and very slight to slight edema. The dermal effects observed after 72 hours generally consisted of slight to distinct incrustation and very slight edema. There were no distinct differences between skin reactions of the intact skin and those of the abraded skin.

On the basis of the present resutls it can be concluded that the substance is a severe primary skin irritant.