Registration Dossier

Diss Factsheets

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study was conducted according to GLP and meets OECD and EEC guideline requirements.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report date:
1990

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Details on test material:
- Name of test material (as cited in study report): T-4388
- Lot/batch No.: Lot 6
- Physical state: Colorless liquid
- Storage condition of test material: Test material was stored in the dark under ambient conditions

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) Limited, Manston Road, Margate, Kent
- Age at study initiation: 6-8 weeks old
- Weight at study initiation: 151-210 g
- Fasting period before study: 19-20 h before dosing and for 1.5-2.5 h post dosing
- Housing: The rats were housed by sex in polypropylene cages with mesh floors suspended over absorbent paper lined trays with a maximum of 6 animals per cage for the dose ranging study and 5 animals per cage for the main study
- Diet (e.g. ad libitum): The rats were fed Expanded Rat and Mouse Maintenance Diet
- Water (e.g. ad libitum): Tap water was available ad libitum throughout the study
- Acclimation period: The rats were allowed an acclimatisation period of at least 9 days before test commencement.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Mean environmental maximum and minimum temperatures were 21ºC and 19 ºC
- Humidity (%): Mean relative humiodity was 40%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 h light/dark cycle (light hours 0700-1900 h)


IN-LIFE DATES: From: 15 February 1990 To: 07 March 1990

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
On the day of dosing, T-4388 was freshly prepared in corn oil. The test material was administered orally in a single dose by means of a gavage at a constant dose volume of 10 ml/kg.

Doses:
Dose Ranging Study- 1000, 2000, 3000, 4000 and 5000 mg/kg
Main Study- 5000 mg/kg
No. of animals per sex per dose:
Dose Ranging Study-2 males and 2 females per dose level
Main Study- 5 male and 5 female rats
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The rats were observed frequently on the day of dosing and once daily for 14 days following dosing. The rats were weighed immediately prior to dosing, 7 days after dosing (main study only) and at sacrifice at the end of the observation period.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
There were no deaths and no abnormalities were detected at necropsy.
Clinical signs:
Clinical signs noted 1/2 h-4 h after dosing, included piloerection and reduced activity.
Body weight:
Body weight gains were acceptable with the exception of one male which showed a lower weight gain than expected.
Gross pathology:
No abnormalities were detected at necropsy.
Other findings:
none

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The median oral lethal dose (LD50) of T-4388 in rats was greater than 5000 mg/kg. Hence, the test material is not classified as per EU classification.
Executive summary:

The acute oral toxicity potential of a test material, T-4388, a colorless liquid, lot 6, was investigated in rats. Fifteen male and fifteen female nulliparous and non-pregnant rats of the Sprague Dawley strain were used. They were 6-8 weeks old and weighed 151-210 g at dosing in the main test.

The rats were housed by sex in polypropylene cages with mesh floors suspended over absorbent paper lined trays with a maximum of 6 animals per cage for the dose ranging study and 5 animals per cage for the main study. The rats were fed Expanded Rat and Mouse Maintenance Diet, except for 19-20 h before dosing and for 1.5-2.5 h post dosing. Tap water was available ad libitum throughout the study.

Mean environmental maximum and minimum temperatures were 21ºC and 19 ºC and mean relative humidity was 40%. Rats were allowed an acclimatization period of at least 9 days before test commencement.

The vehicle used for the dosing solution was corn oil. The test material was administered orally in single dose by means of a gavage at a constant dose volume of 10 ml/kg. The rats were observed frequently on the day of dosing and once daily for 14 days following dosing. They were weighed immediately prior to dosing, 7 days after dosing (main study only) and at sacrifice at the end of the observation period. At the end of the observation period and sacrifice by carbon dioxide asphyxiation, each animal was subjected to necropsy.

A dose ranging study in pairs of rats indicated that the oral LD50 value was greater than 5000 mg/kg. A main study dose level of 5000 mg/kg was selected accordingly. No further testing at other dose levels was necessary.

In the main study, no deaths occurred after administration of T-4388 at a dose level of 5000 mg/kg. Clinical signs noted ½ h-4 h after dosing, included piloerection and reduced activity. No abnormalities were detected at necropsy.

The median oral lethal dose (LD50) of T-4388 was greater than 5000 mg/kg. Hence, the test material is not classified as per EU classification.