Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
13 June 2000 - 3 July 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Tetra-C6-10-(even and linear)-alkyl benzene-1,2,4,5-tetracarboxylate
EC Number:
700-623-4
Molecular formula:
C34H54O8 - C50H86O8
IUPAC Name:
Tetra-C6-10-(even and linear)-alkyl benzene-1,2,4,5-tetracarboxylate

Test animals

Species:
rat
Strain:
other: Sprague-Dawley CD (Crl : CD ® (SD) IGS BR)
Sex:
male/female
Details on test animals or test system and environmental conditions:
Male and female Sprague-Dawley CD (Crl : CD ® (SD) IGS BR) strain rats supplied by Charles River (UK) Ltd, Margate, Kent, UK were used. At the start of the study the males weighed 203 to 221 g, and the females 201 to 229g, and were eight to twelve weeks old. After an acclimatisation period of at least five days the animals were selected at random and given a number unique within the cage by tail marking.

The animals were housed in groups of three by sex in solid-floor polypropylene cages furnished with woodflakes. With the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing, free access to mains drinking water and food (Rat and Mouse Expanded Diet No.1, Special Diets Services Limited, Witham, Essex, UK) was allowed throughout the study.

The temperature and relative humidity were set to achieve limits of 19 to 25 °C and 30 to 70 % respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was approximately fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light and twelve hours darkness.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The information available suggested a starting dose of 2000 mg/kg. The testing sequence followed the flow chart attached below.
Groups of fasted animals were therefore treated as follows:

DOSE LEVEL (mg/kg) SPECIFIC GRAVITY DOSE VOLUME (ml/kg) NUMBER OF RATS
MALE FEMALE
2000 0.970 2.07 3
2000 0.970 2.07 3

All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted bodyweight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each sex to confirm the survival of the previously dosed animals.
Doses:
2000 mg/kg
No. of animals per sex per dose:
3 animals per sex per dose
Control animals:
no
Details on study design:
The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.
Individual bodyweights were recorded prior to dosing and seven and fourteen days after treatment.
At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities for examination of major organs. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Statistics:
The number of animals dying during the study, or killed for humane reasons, was determined. The nature, severity, time of onset and duration of toxic effects were also determined. Effects on bodyweights and abnormalities noted at necropsy were identified.
Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test material was made as shown in the schematic diagram in the attached file.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
There were no signs of systemic toxicity.
Body weight:
All animals showed an expected gain in bodyweight during the study.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
No additional findings reported.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was estimated to be greater than 2000 mg/kg bodyweight.
No mortalities were noted at 2000 mg/kg bodyweight.
No classification and labelling are required according to the EU regulations.
Executive summary:

A study was performed to assess the acute oral toxicity of the test material following a single oral administration to the Sprague-Dawley CD strain rat according to EU Test Method B.1 tris (744/099).

Using all available information, 2000 mg/kg bodyweight was selected as the starting dose.

A group of three fasted males was treated with the starting dose. This was followed by a group of three fasted animals of the other sex at the same dose level.

The undiluted test material was administered orally. The animals were observed ½, 1, 2 and 4 hours after dosing and then once daily for fourteen days. Bodyweights were recorded on Day 0 (day of dosing) and on Days 7 and 14. At the end of the observation period all animals were killed by cervical dislocation and subjected to gross necropsy.

There were no deaths.

There were no signs of systemic toxicity.

All animals showed expected gains in bodyweight over the study period.

No abnormalities were noted at necropsy.

The acute oral median lethal dose, (LD50) of the test material, in the Sprague-Dawley CD strain rat, was estimated as being greater than 2000 mg/kg bodyweight. No mortalities were noted in animals treated with 2000 mg/kg bodyweight.