Bontron E-108

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

01 March 2000 to 23 March 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted 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 relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

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)

Remarks:

Date of inspection: March 23rd 1998 Date of signature: July 21st 1998

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Details on test material:

Sponsor's identification :S178207/1
Batch number :SI/2000/013-NBZ0166/44
Date received :14 February 2000
Description :off white powder
Storage conditions :room temperature in the dark

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, UK
- Age at study initiation: eight to twelve weeks old.
- Weight at study initiation: males weighed 210 to 240 g, and the females 212 to 224 g
- Fasting period before study: Overnight fast immediately before study
- Housing: The animals were housed in groups of three by sex in solid-floor polypropylene cages furnished with woodflakes.
- Diet: ad libitum - Rat and Mouse Expanded Diet No.1, Special Diets Services Limited, Witham, Essex, UK.
- Water: ad libitum - mains drinking water
- Acclimation period: acclimatisation period of at least five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): approximately fifteen changes per hour
- Photoperiod (hrs dark / hrs light): controlled by a time switch to give twelve hours continuous light and twelve hours darkness.


IN-LIFE DATES: From: Day 0 To: Day 14

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: not stated in report
- Amount of vehicle (if gavage): 10 ml/kg - The volume administered to each animal was calculated according to the fasted bodyweight at the time of dosing.
- Justification for choice of vehicle: not stated in report
- Lot/batch no. (if required): not stated in report
- Purity: not stated in report


MAXIMUM DOSE VOLUME APPLIED: The volume administered to each animal was calculated according to the fasted bodyweight at the time of dosing. (Not described in any more detail in report).


DOSAGE PREPARATION (if unusual):not applicable


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: the use of all available information

Doses:

2000 mg/kg

No. of animals per sex per dose:

3 females and then 3 males

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: 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 or death.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight

Statistics:

Determination of LD50

Results and discussion

Preliminary study:

One female found dead during the day of dosing.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Two animals (one male and one female) were found dead during the day of dosing.

Clinical signs:

Clinical signs of toxicity commonly noted were ataxia, hunched posture, lethargy, decreased respiratory rate, laboured or noisy respiration and splayed or tiptoe gain with incidents of pallor of the extremities and emaciation.

Body weight:

The surviving animals showed expected gains in bodyweight over the study period.

Gross pathology:

Abnormalities noted at necropsy of animals that died during the study were haemorrhagic lungs, dark liver and dark kidneys. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Other findings:

- Organ weights: not determined
- Histopathology: not determined
- Potential target organs: not determined
- Other observations: none

Any other information on results incl. tables

The acute oral LD₅₀of the test material, S178207/1, in the Sprague-Dawley CD strain rat was estimated to be greater than 2000 mg/kg bodyweight.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral LD50 of the test material, S178207/1, in the Sprague-Dawley CD strain rat was estimated to be greater than 2000 mg/kg bodyweight, therefore no symbol and risk phrase are required according to EU labelling 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. 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 B1 tris of Commission Directive 96/54/EC (which constitutes Annex V of Council Directive 67/548/EEC).

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. This was followed by a group of three fasted animals of the other sex at the same dose level.The test material was administered orally as a suspension in arachis oil BP. The animals were observed ½, 1, 2 and 4 hours after dosing and then once daily for up to fourteen days. Bodyweights were recorded on Day 0 (day of dosing) and on Days 7 and 14, or at death. At the end of the observation period all the surviving animals were killed by cervical dislocation and all animals were subjected to gross necropsy.

Two animals (one male and one female) were found dead during the day of dosing.

Clinical signs of toxicity commonly noted were ataxia, hunched posture, lethargy, decreased respiratory rate, laboured or noisy respiration and splayed or tiptoe gain with incidents of pallor of the extremities and emaciation.

 

The surviving animals showed expected gains in bodyweight over the study period. Abnormalities noted at necropsy of animals that died during the study were haemorrhagic lungs, dark liver and dark kidneys. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

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 symbol and risk phrase are required according to EU labelling regulations.