Warfarin

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Insufficient information about study methodology, animals, and results.

Data source

Reference

Reference Type:

publication

Title:

The Toxicity of 3-(Acetonylbenzyl)-4-Hydroxycoumarin (Warfarin) to Laboratory Animals

Author:

Hagan EC, Radomski JL

Year:

1953

Bibliographic source:

Journal of the American Pharmaceutical Association XLII(6), 379-382

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The lethal dose of warfarin to a number of different animal receptors was evaluated.

Test type:

other: acute and subacute toxicity, methodology not outlined

Test material

Test material information

Constituent 1

Reference substance name:

Warfarin

EC Number:

201-377-6

EC Name:

Warfarin

Cas Number:

81-81-2

Molecular formula:

C19H16O4

IUPAC Name:

4-hydroxy-3-(3-oxo-1-phenylbutyl)-2H-chromen-2-one

Constituent 2

Reference substance name:

3(acetonybenzyl)-4-hydroxycoumarin

IUPAC Name:

3(acetonybenzyl)-4-hydroxycoumarin

Test animals

Species:

rat

Strain:

Osborne-Mendel

Sex:

male/female

Details on test animals or test system and environmental conditions:

Food and water ad libitum.

Administration / exposure

Route of administration:

oral: feed

Vehicle:

not specified

Details on oral exposure:

Added to food.

Doses:

1, 3, 6.25, 12.5, 25, 50, 100, and 250 ppm.

No. of animals per sex per dose:

4-6 animals per dose group (equal number of each sex.)

Control animals:

no

Results and discussion

Effect levels

Remarks on result:

other: 250 and 50 ppm warfarin were found more toxic to rats than 10 ppm when fed for periods from one to five days. However, levels of 10 ppm are as toxic when fed for longer periods.

Clinical signs:

other: Symptoms and gross autopsy findings from acute doses were variable depending on the time of death. Convulsions were observed in animals which succumbed within several hours after receiving the very highest doses by stomach tube. In animals dying delayed

Applicant's summary and conclusion

Conclusions:

250 and 50 ppm warfarin were found more toxic to rats than 10 ppm when fed for periods from one to five days. However, levels in the neighborhood of 10 ppm are as toxic as 250 and 50 ppm when fed for longer periods.