Diisopropylbenzene hydroperoxide

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Diisopropylbenzene hydroperoxide

EC Number:

247-988-1

EC Name:

Diisopropylbenzene hydroperoxide

Cas Number:

26762-93-6

Molecular formula:

C12H18O2

IUPAC Name:

reaction mass of 1-(3-isopropylphenyl)-1-methylethyl hydroperoxide and 1-(4-isopropylphenyl)-1-methylethyl hydroperoxide

Test material form:

liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Test animals:
Species, strain: rat, Sprague-Dawley Rj: SD (IOPS Han).
Reason for this choice: rodent species generally accepted by regulatory authorities for this type of study.
Breeder: Janvier, Le Genest-Saint-Isle, France.
Number and sex: one group of ten animals (five males and five females).
Females were nulliparous and non-pregnant.
Age/weight: on the day of treatment, the animals were approximately 8 weeks old and had a mean body weight ± standard deviation of 312 ± 8 g for the males and 219 ± 8 g for the females.
Acclimation: at least 5 days before the beginning of the study.
Identification: individually by earnotches.

Environmental conditions:
The conditions in the animal room were set as follows:
• temperature: 22 ± 2°C
• relative humidity: 30 to 70%
• light/dark cycle: 12 h/12 h
• ventilation: approximately 12 cycles/hour of filtered, non-recycled air.
• food and water ad libitum

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

On the day before treatment, the dorsal area of each animal was clipped (i.e. approximately 5 cm x 7 cm for males and 5 cm x 6 cm for females) using an electric clipper. Only animals with healthy intact skin were used for the study. The test item was applied undiluted at the dose-level of 2000 mg/kg, taking into consideration that its specific gravity was 0.93 g/mL. The volume of administration was therefore 2.15 mL/kg.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw for diisopropylbenzene hydroperoxide in its solvent
1118 mg/kg bw for diisopropylbenzene hydroperoxide

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

The animals were observed frequently during the hours following administration of the test item, for detection of possible treatment-related clinical signs. Thereafter, observation of the animals was made at least once a day until day 15.
Type, time of onset and duration of clinical signs were recorded for each animal individually. The animals were weighed individually just before administration of the test item on day 1 and then on days 8 and 15.
The body weight gain of the treated animals was compared to that of CIT control animals with a similar initial body weight. On day 15, all animals were killed by carbon dioxide asphyxiation. All study animals were subjected to a macroscopic examination as soon as possible after death.
After opening the thoracic and abdominal cavities, a macroscopic examination of the main organs (digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organs with obvious abnormalities) was performed.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Remarks:

Luperox DH

Effect levels 2

Sex:

male/female

Dose descriptor:

LD0

Effect level:

1 118 mg/kg bw

Based on:

act. ingr.

Remarks:

diisopropylbenzene hydroperoxide

Mortality:

No deaths occurred during the study.

Clinical signs:

other: No systemic clinical signs were observed during the study. Only dryness of the skin was noted in all animals from day 4 up to day 13. No other cutaneous reactions were recorded during the study.

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 diisopropylbenzene hydroperoxide is higher than 1118 mg/kg in rats.

Executive summary:

The acute dermal toxicity of Luperox DH (diisopropylbenzene monohydroperoxide at 55.9% in diisopropylbenzene) was evaluated in rats according to OECD N°402 guideline. One groups of 5 male and 5 female Sprague Dawley rats was given a single dermal dose of Luperox DH at doses of 2000 mg/kg (equivalent to 1118 mg/kg of diisopropylbenzene monohydroperoxide). Following treatment, rats were observed daily and weighted weekly. A gross necropsy examination was performed at the time of scheduled euthanasia (Day 14).

No systemic clinical signs and no deaths were observed during the study. Only dryness of the skin was noted in all animals from day 4 up to day 13. No other cutaneous reactions were recorded during the study. A slightly reduced weight gain was seen in 1/5 males and 2/5 females during the second week of the study. The overall body weight gain of the other animals was similar to that of historical control animals. No apparent abnormalities were observed at necropsy in any animal.

Under these experimental conditions, the dermal LD0 in rats of the Luperox DH is higher than 2000 mg/kg (equivalent to 1118 mg/kg of diisopropylbenzene monohydroperoxide).