Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
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 402 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

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

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Animals:
Species, strain: rat, Sprague-Dawley ICO: OFA-SD (IOPS Caw).
Reason for this choice: rodent species generally accepted by regulatory authorities for this type
of study.
Breeder: lffa Crédo, 69210 L'Arbresle, France.
Number and sex: one group of ten animals (five males and five females).
Age/weight: on the day of treatment, the animals were approximately 8 weeks old, and had a mean body weight ± standard deviation of 262 ± 15 g for the males and 235 ± 8 g for the females.
Acclimatization: at least 5 days before the beginning of the study.
Identification of the animals: the animals were identified individually by earmarks or earnotches.

Environmental conditions:
. temperature: 21 ± 2°C
. relative humidity: 30 to 70%
. light/dark cycle: 12 hl12 h
. ventilation: approximately 12 cycles/hour of filtered, non-recycled air.
The temperature and relative humidity were under continuous control and recording.
During the acclimatization period, one to seven animals of the same sex were housed in polycarbonate cages. During the treatment period, the animals were housed individually in polycarbonate cages.
Food and water ad libitum. No contaminants were known to have been present in the diet, drinking water or bedding material at levels which may be expected to have interfered with or prejudiced the outcome of the study.


Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
On the day before treatment, the dorsal area (6 cm x 8 cm) of each animal was clipped using electric clippers. Only animais with healthy intact skin were used for the study.
The test substance was applied undiluted taking into consideration that its specific gravity was 0.932 g/ml. It was placed directly on an area of the skin representing approximately 10% (5 cm x 6 cm for the females and 5 cm x 7 cm for the males) of the body surface of the animals. A hydrophilic gauze pad was then applied to the skin. The test substance and the gauze pad were held in contact with the skin for 24 hours by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage. This dressing prevented ingestion of the test substance by the animals. No residual test substance was observed at removal of the dressing. The dose applied to each animal was adjusted according to body weight determined on the day of treatment.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
other: historical laboratory controls
Details on study design:
Post observation period : 14 days.
The animals were observed frequently during the hours following administration of the test substance, for detection of possible treatment-related clinical signs. Thereafter, observation of the animals was made at least once a day until day 15.
The animals were weighed individually just before administration of the test substance on day 1 and the days 8 and 15.
On day 15, all animals were killed by carbon dioxide asphyxiation and a macroscopic examination was performed. (digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organs with obvious abnormalities). In case of macroscopic lesions, organ samples were taken and preserved in 10% buffered formalin.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There was no mortality.
Clinical signs:
No clinical signs were observed.
Body weight:
A reduced weight gain or slight bodyweight loss were observed in two females during the observation period. The overall body weight gain of the other animals was not affected by treatment with the test substance.
Gross pathology:
Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD0 of the test substance tert-butyl-cumyl peroxide equal to or higher than 2000 mg/kg in rats.
Executive summary:

Peroximon 801 (96.8% tert-butyl-cumyl peroxide) was applied to the skin of one group of ten Sprague-Dawley rats (five males and five females), in a well conducted acute dermal toxicity test (OECD 402, GLP). The application was performed with the undiluted test substance at the dose of 2000 mg/kg. The test site was then covered by a semi-occlusive dressing for 24 hours. Clinical signs, mortality and body weight gain were checked for a period of 14 days following the single application of the test substance.All animals were subjected to necropsy. The general behaviour of the animals was not affected by treatment with the test substance.

A reduced weight gain or slight bodyweight loss were observed in two females during the observation period. The overall body weight gain of the ether animals was not affected by treatment with the test substance. No cutaneous reactions were observed. No death occurred at 2000 mg/kg. No apparent abnormalities were observed at necropsy. The dermal LD0 of Peroximon 801 was equal to or higher than 2000 mg/kg bw in rats.