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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:
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:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
17th July 1992
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals 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

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
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
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
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 96h
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.