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Toxicological information

Acute Toxicity: oral

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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

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent

Test animals

Species:
rat
Strain:
Osborne-Mendel
Sex:
male/female
Details on test animals 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:
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 deaths, convulsions were never observed but hemorrhage was found in one or several tissues. In addtiion, the animals' appearance was marked by ruffled coat, pallor and extreme lassitude. Death occurred in prostration.

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.