tert-butyl α,α-dimethylbenzyl peroxide

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

17th July 1992

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

tert-butyl α,α-dimethylbenzyl peroxide

EC Number:

222-389-8

EC Name:

tert-butyl α,α-dimethylbenzyl peroxide

Cas Number:

3457-61-2

Molecular formula:

C13H20O2

IUPAC Name:

[2-(tert-butylperoxy)propan-2-yl]benzene

Test material form:

liquid

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Animals:
Sex, species, strain: male New Zealand White rabbits.
Reason for this choice: species generally accepted by regulatory authorities for this type of study. Breeder. Elevage Cunicole de Val de Selle, 80160 Prouzel, France.
Number of animals: three animals were used, as recommended by the international guidelines. Identification: the animals were identified individually with a metal ear tag.
Weight: on the day of treatment, the animals had a mean body weight ± standard deviation of
2.4±0.1 kg.
Acclimatization: at least 5 days before the beginning of the study.

Environmental conditions:
. temperature: 18 ± 3°C
. relative humidity: 30 to 70%
. light/dark cycle: 12 h/12 h
. ventilation: approximately 12 cycles/hour of filtered, non-recycled air.
The temperature and relative humidity were under continuous control and recording. The records were checked daily and filed. In addition to these daily checks, the housing conditions and corresponding instrumentation and equipment were verified and calibrated at regular intervals. The animals were housed individually in polystyrene cages (48.2 cm x 58 cm x 36.5 cm).
Each cage was equipped with a food container and a water bottle.

Food and water ad libitum

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

The test substance was used undiluted (0.5 ml)

Duration of treatment / exposure:

As possible irritant effects were anticipated, the test substance was evaluated in one animal in a first assay. The duration of exposure was 3 minutes on one flank and 4 hours on the other flank. Since the test substance was not strongly irritant in this first assay, it was then applied for
4 hours to two other animals in a second assay.

Observation period:

- 72 hours when there was no evidence of dermal irritation after 72 hours
- until day 15 when there was persistent cutaneous irritation after 72 hours

Number of animals:

3

Details on study design:

Doses of 0.5 ml of the test substance were placed on a 6 cm 2 dry gauze pad, which was then applied to the right flank (application for 4 hours) or the left flank (application for 3 minutes) of the animals. The test substance and the gauze pad were held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 96h

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 96h

Irritant / corrosive response data:

After a 3-minute exposure (one animal): No cutaneous reactions were observed.
After a 4-hour exposure (three animals): No cutaneous reactions were observed in one animal.
In the two other animals, a very slight or well-defined erythema (grade 1 or 2) was noted between days 1 and 6 and a slight oedema (grade 2) was recorded on days 2, 3 and 4.
Dryness of the skin was observed in these animals from day 5 up to the end of the observation period (day 15).
Mean scores over 24, 48 and 72 hours for each animal were 0.0, 2.0 and 2.0 for erythema and
0.0, 2.0 and 2.0 for oedema. All the scores were 2 for animal 2 and 3, at 24, 48 and 72 hours

Other effects:

Any change in the animal behaviour was noted.

Applicant's summary and conclusion

Interpretation of results:

Category 3 (mild irritant) based on GHS criteria

Conclusions:

t-BUTYL-CUMYL PEROXIDE is mildly irritating when applied topically to rabbits.

Executive summary:

The acute dermal irritation of Peroximon 801 (96.8 % tert-butyl cumyl peroxide) was evaluated in rabbits according to OECD 404 guideline (GLP study). The substance was applied undiluted to the skin of 1 New-Zealand White albino rabbit and held in contact for 3 minutes or 4 hours by means of a semi-occlusive dressing. As no irritation was observed after the 3-minute exposure, the substance was applied to two other animals for 4 hours. Mean scores over 24, 48 and 72 hours for each animal were evaluated for erythema and for oedema. Animals were then observed daily until day 15. After a 4-hour exposure (three animals): No cutaneous reactions were observed in one animal. In the two other animals, a very slight or well-defined erythema was noted between days 1 and 6 and a slight oedema was recorded on days 2, 3 and 4. Dryness of the skin was observed in these animals from day 5 up to the end of the observation period (day 15). Mean scores over 24, 48 and 72 hours for each animal were 0.0, 2.0 and 2.0 for erythema and 0.0, 2.0 and 2.0 for oedema.