Di-tert-butyl 1,1,4,4-tetramethyltetramethylene diperoxide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

4 January 1993 - 2 February 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well-conducted and documented study performed according to established guidelines and GLP. Report includes COA of test material.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Di-tert-butyl 1,1,4,4-tetramethyltetramethylene diperoxide

EC Number:

201-128-1

EC Name:

Di-tert-butyl 1,1,4,4-tetramethyltetramethylene diperoxide

Cas Number:

78-63-7

Molecular formula:

C16H34O4

IUPAC Name:

2,5-bis(tert-butylperoxy)-2,5-dimethylhexane

Details on test material:

A slightly yellow liquid, further identified by the Batch No. 0029208030427, the CAS No. 78-63-7 and the EINECS No. 2011281. It was stated to be 2,5-Bis(tert-butylperoxy)-2,5-dimethylhexane in solvent and was 94.1% pure.

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

Young adult rats of the CD strain (remote Sprague-Dawley origin) were supplied by Charles River (U.K.) limited, Margate, Kent, England. The animals were bred under barriered conditions and travelled from the supplier to the animal holding room in sealed boxes with filter protected air-vents. The animals were housed in stainless steel grid cages. Five animals of the same sex were accommodated in each cage.

The animals were held in a limited-access facility. All rooms were kept at slight positive pressure relative to the outside and each had its own filtered air supply giving approximately 15 complete air changes per hour without re-circulation. A temperature range of 18 - 21 °C and a relative humidity range of 38 - 57% were achieved. Electric tim-switches regulated a lighting cycle of 12 hours of artificial light per day.

A commercially-available complete pelleted rodent diet was fed without restriction except for the removal of food for approximately 18 hours before administration of the test material. The manufacturer supplied analytical data with each batch of diet which included concentrations of nutritional components, aflatoxins and selected heavy metals, pesticides and micro-organisms. The diet contained no antibiotic or other chemotherapeutic or prophylactic treatment. Animals had free access to tap water taken from the public supply. Certificates of analysis were routinely received from the supplier (Suffolk Water Company).

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

maize oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20% w/v
- Amount of vehicle (if gavage):
- Justification for choice of vehicle: not specified in report
- Lot/batch no. (if required):
- Purity:

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

DOSAGE PREPARATION (if unusual): The dosage was calculated and expressed gravimetrically in terms of the material as received. A fresh formulation of the test material was prepared shortly before administration and any surplus remaining after dosing was destroyed on the same day.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:

Doses:

2000 mg/kg

No. of animals per sex per dose:

Five

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Three separate inspections were made during the first hour after dosing and two further inspections during the remainder of Day 1. From Day 2 onwards, the animals were inspected twice daily (morning and afternoon). The type, time of onset and duration of reactions to treatment were recorded. The test was terminated on the morning of Day 15.
- Necropsy of survivors performed: yes. Each animal was thoroughly examined for abnormality of tissues or organs. All body cavities were opened, larger organs were sectioned and the gastro-intestinal tract was opened at intervals for examination of the mucosal surfaces. All abnormalities were described or the normal appearance of major organs was confirmed.
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: Clinical signs, see above. The bodyweight of each animal was recorded on the day before dosing and on Days 1, 8 and 15. Histopathology was not performed.

Statistics:

None

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortalities at 2000 mg/kg

Mortality:

None in males or females

Clinical signs:

other: None in males or females

Gross pathology:

Necropsy, on Day 15, revealed no significant macroscopic lesions.

Other findings:

None reported.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the acute oral median lethal dosage (LD50) of the test material was greater than 2000 mg/kg.
Based on these results, the test item does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2017) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).

Executive summary:

The acute oral toxicity of the substance was investigated in a group of five male and five felame CD rats at a dosage of 2000 mg/kg. Mortality and signs of reaction to treatment were recorded during a subsequent 14 -day observation period. The animals were killed on the following day and subjected to necropsy.

There was no death and no sign of reaction to treatment. The animals achieved expected bodyweight gains and necropsy revealed no significant macroscopic lesions.

Under the conditions of this study, the acute oral median lethal dosage (LD50) of the test material was greater than 2000 mg/kg.