416-730-1

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline conform

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Test material

Test material information

Constituent 1

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Equal numbers of healthy male and female CD rats of Sprague-Dawley origin (Hsd/Ola:Sprague-
Dawley(CD)) were obtained from Harlan Olac Ltd., Bicester, Oxon, England.
They were in the weight range of 88 to 111 g and approximately four to seven weeks of age prior
to dosing (Day 1) in the main study. All the rats were acclimatised to the experimental environment
for a period of five days prior to the start of the main study.
The rats were allocated without conscious bias to cages within the treatment group. They were
housed in groups of up to five rats of the same sex in metal cages with wire mesh floors in Building
R14 Room 6.
A standard laboratory rodent diet (Biosure LAD 1) and drinking water were provided ad libitum.
Access to food only was prevented overnight prior to and approximately 4 hours after dosing.
The batch(es) of diet used for the study was analysed for certain nutrients, possible contaminants and
micro-organisms.
Results of routine physical and chemical examination of drinking water at source, as conducted,
usually weekly by the supplier, are made available to Huntingdon Research Centre Ltd. (as quarterly
summaries).
The mean daily minimum and maximum temperatures of the animal room were 21 °C and 24°C
respectively and the mean daily relative humidity value was 56% R.H. Air exchange was maintained
at 10 to 15 air changes per hour and lighting was controlled by means of a time switch to provide
12 hours of artificial light (0700 - 1900 hours) in each 24-hour period.
Each animal was identified by cage number and ear punching. Each cage was identified by a
coloured label displaying the dose level, study schedule number, animal mark and the initials of the
Study Director and Home Office licensee.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

The appropriate dose volume of the test substance was administered to each rat by oral gavage using a syringe and plastic catheter (8 choke).
The day of dosing was designated Day 1.

Doses:

2 g/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- duration of observation period following administration: 14d
- frequency of observation : twice a day
- frequency of weighting: at day 1-4, 8, 15

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: no mortality and no signs of specific toxicity observed

Mortality:

none

Clinical signs:

- Piloerection was observed in all rats within five minutes of dosing and throughout the remainder of day 1
- yellow discolouration of the faeces was evident for all animals on day 2 only

Body weight:

- All rats achieved anticipated bodyweight gains throughout the study

Gross pathology:

No macroscopic abnormalities were observed for animals killed on Day 15.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute lethal oral dose to rats was found to be greater than 2.0 g/kg bodyweight.

Executive summary:

A group of ten fasted rats (five males and five females) was given a single dose by gavage of the test substance, formulated in distilled water, at a dose level of 2.0 g/kg bodyweight. All animals were killed and examined macroscopically on Day 15, the end of the observation period.

There were no deaths. Clinical signs of reaction to treatment were limited to piloerection, recovery was complete by Day 2. However, a yellow discolouration of the faeces was evident for all animals on Day 2 only. All rats achieved the anticipated bodyweight gains throughout the study. No abnormalities were recorded at the macroscopic examination on Day 15.

The acute lethal oral dose to rats was found to be greater than 2.0 g/kg bodyweight.