Warfarin

Acute Toxicity: other routes

Administrative data

Endpoint:

acute toxicity: other routes

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Insufficient information. No weight or age of test subjects. Environmental conditions also not described. No data on control animals. The number of test subjects is inappropriate

Data source

Reference

Reference Type:

publication

Title:

Some Anticoagulant Properties of 2-Acyl-1,3-indandiones and Warfarin in Rabbits

Author:

Heisey SR, Saunders JP, Olson KC

Year:

1956

Bibliographic source:

Journal of Agricultural and Food Chemistry 4, 144-147

Materials and methods

Test guideline

Qualifier:

no guideline available

GLP compliance:

not specified

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

Details on test material:

- Name of test material (as cited in study report): Warfarin.
- Physical state: Liquid.

Test animals

Species:

rabbit

Strain:

other: mixed breed

Sex:

male/female

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

not specified

Details on exposure:

Coagulation time was determined at pre-test and at 2, 8, 24, 48, 72, and 96 hours.

Doses:

Warfarin was tested at a single dose of 40 mg/kg and 5 mg/kg.

No. of animals per sex per dose:

2 animals per dose. Sex of test animals in each test group not provided.

Control animals:

other: Same animals used as pre-test controls

Details on study design:

Blood was drawn from a marginal ear vein into a syringe contining 0.1M sodium oxalate and then centrifuged and the plasma drawn off. Oxalated plasma was added to a test tube and thromboplastin was added. After mixing, 0.2M calcium chloride was added and a stopwatch was started. The mixture was agitated and observed. When the first threads of fibrin clot were observed, the watch was stopped and the time noted. This was the plasma coagulation time. The ratio of the plasma coagulation time post-dosing and the plasma coagulation time pre-dosing was calculated at 2, 8, 24, 48, 72, and 96 hours.

Results and discussion

Effect levels

Remarks on result:

other: The amount of warfarin injected appeared to have little effect on the extent of increase in plasma coagulation time, which was approximately four times the normal value whether a dose of 5 mg/kg or of 40 mg/kg was given.

Other findings:

The amount of warfarin injected appeared to have little effect on the extent of increase in plasma coagulation time, which was approximately four times the normal value whether a dose of 5 mg/kg or of 40 mg/kg was given.

Any other information on results incl. tables

Plasma Coagulation Times in Rabbits after Single Intraperitoneal Dose of Warfarin

	Time After Administration (hours)
Dose Level	0 hr	2 hr	8 hr	24 hr	48 hr	72 hr	96 hr
40 mg/kg	9.6	12	10.2	16.6	36.7	18.3	14.8
5 mg/kg	7.9	11.6	11	21.9	35.2	13.6	11.7

Applicant's summary and conclusion

Conclusions:

When given in a single dose, warfarin increased coagulation time by approximately four times, but the amount injected had little effect on the extent of the increase.