Butyl 4,4-bis(tert-butyldioxy)valerate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

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:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Butyl 4,4-bis(tert-butyldioxy)valerate

EC Number:

213-626-6

EC Name:

Butyl 4,4-bis(tert-butyldioxy)valerate

Cas Number:

995-33-5

Molecular formula:

C17H34O6

IUPAC Name:

butyl 4,4-bis(tert-butylperoxy)pentanoate

Test material form:

other: colorless liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Iffa Credo, 69210 L'Arbresle,. France.
- Age at study initiation: 8 weeks old
- Weight at study initiation: of 252 ± 10 g for the males and 225 ± 11 g for the female
- Housing: individually in polycarbonate cage
- Diet: A04 C pelleted diet, ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2
- Humidity (%): 30-70
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back, approximately 7 cm x 5 cm for males and 6 cm x 5 cm for females
- % coverage: ca. 10
- Type of wrap if used: aerated hypoallergenic dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no

Duration of exposure:

24 hours

Doses:

2000 and 4000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

CLINICAL EXAMINATIONS
Morbidity and mortality
Each animal was checked for mortality and morbidity, once a day during the acclimation period, frequently during the hours following administration, then once a day until the end of the observation period, including weekends.

Clinical signs
Each animal was observed after treatment as follows:
at least once during the first 30 minutes, periodically during the first 4 hours, then once a day, at approximately the same time, for the recording of clinical signs.
Any clinical signs observed were recorded individually for each animal, along with the times of onset and recovery.

Body weight
The body weight of each animal was recorded on the day of group allocation then on the day of treatment and on Days 8 and 15.
The body weight gain of the test item-treated animals was compared to that of CiToxLAB France historical control data generated from animals of the same strain and age treated with drinking water treated by reverse osmosis under similar experimental conditions.

PATHOLOGY
Euthanasia
On completion of the observation period, all animals were deeply anesthetized by an intraperitoneal injection of pentobarbital sodium and euthanized by exsanguination.

Macroscopic post-mortem examination
A macroscopic post-mortem examination was performed on all animals. 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. All gross observations were recorded individually for each animal.

Preservation of tissues
For all animals, the macroscopic lesions were preserved in 10% buffered formalin.
Any histological specimens (tissues in fixative) were destroyed at the finalization of the study report.

Microscopic examination
No microscopic examination was performed.

Statistics:

None

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LD0

Effect level:

>= 4 000 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Effect levels 2

Key result

Sex:

male/female

Dose descriptor:

LD0

Effect level:

>= 2 000 mg/kg bw

Based on:

act. ingr.

Remarks:

Di-n-butyl-4,4'-Di(tert-butylperoxy)

Mortality:

No unscheduled deaths occurred during the study.

Clinical signs:

No clinical signs and no cutaneous reactions were observed during the study.

Body weight:

A reduced weight gain or a slight body weight loss was seen in females given 4000 mg/kg.
The body weight gain of the other treated animals was similar to that of CIT historical control animals

Gross pathology:

Macroscopic examination of the main organs of the animals revealed no apparent abnorrnalities.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information

Conclusions:

The derrnal LD0 of LUPEROX 230M50 is equal to or higher than 4000 mg/kg in rats, which corresponds to a dose-level of 2000 mg/kg of Di-n-butyl-4,4'-Di(tert-butylperoxy).

Executive summary:

The  acute  dermal  toxicity  of  LUPEROX 230M50 was evaluated in rats according to OECD guideline No. 402 and the principles of Good Laboratory Practice Regulations. The test substance was applied at the dose-levels of 2000 mg/kg and 4000 mg/kg to the skin of groups of ten Sprague-Dawley rats (five males and five females each). The application was performed  with the undiluted test substance, taking into consideration that its specific gravity was 0.84 g/ml. 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.

No clinical signs and no deaths were observed during the study. No cutaneous reactions were observed. A reduced weight gain or a slight body weight loss was seen in females given 4000 mg/kg. The body weight gain of the other animals was not affected by treatment with the test substance. No apparent abnormalities were observed at necropsy in any animal.

The dermal LD0  of LUPEROX  230M50 is equal to or higher than  4000 mg/kg in rats, which corresponds to a dose-level of 2000 mg/kg of Di-n-butyl-4,4'-Di(tert-butylperoxy).