Phytosteryl Macadamiate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2000-01-10 - 2000-06-19

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The GLP-study was conducted according an internationally accepted guideline.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (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

Test material information

Constituent 1

Test material form:

semi-solid (amorphous): gel

Remarks:

migrated information: paste

Test animals

Species:

rat

Strain:

Sprague-Dawley

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 212 to 215g, and the females 215 to 226g, 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:

arachis oil

Details on oral exposure:

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

Control animals:

no

Details on study design:

The animals were observed for deaths or overt signs of toxicity 0.5, 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 all animals were killed by cervical dislocation and 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.

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:

No signs of systemic toxicity were noted.

Body weight:

Animals showed expected gain in bodyweight during the study period.

Gross pathology:

No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral median lethal dose, (LDS0) of the test material, YOFCO MAS LOT NO. 92506, 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.

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. The method followed that in the OECD Guidelines for Testing of Chemicals No. 423 "Acute Oral Toxicity - Acute Toxic Class Method" (adopted 22 March 1996) and Method B1trisof Commission Directive 96/54/EC (which constitutes Annex V of Council Directive 67/548/EEC).

The results may be used as a basis for classification and labelling under Annex VI of Council Directive 67/548/EEC (as adapted to technical progress by Commission Directive 93/21/EEC) relating to the classification, packaging and labelling of dangerous substances.

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

A group of three fasted females was treated with the starting dose of 2000 mg/kg bodyweight. This was followed by a group of three fasted males at the same dose level. Dosing was performed sequentially.

The test material was administered orally as a solution in arachis oil BP. The animals were observed Vi, 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.