United States
Environmental Protection
Agency
Pesticides And
Toxic Substances
(H-7508W)
21T-1014
June 1991
R.E.D. FACTS
Warfarin
Pesticide All pesticides sold or used in the United States must be
Reregistration registered by EPA, based on scientific studies showing that they can be
used without posing unreasonable risks to people or the environment.
Because of advances in scientific knowledge, the law requires that
pesticides which were first registered years ago be reregistered to
ensure that they meet today's more stringent standards.
In evaluating pesticides for reregistration, EPA obtains from
pesticide producers and reviews a complete set of studies showing the
human health and environmental effects of each pesticide. The
Agency imposes any regulatory controls that are needed to effectively
manage each pesticide's risks. EPA then reregisters pesticides that can
be used without posing undue hazards to human health or the
environment.
When a pesticide is eligible for reregistration, EPA announces
this and explains why in a Reregistration Eligibility Document, or
RED. This fact sheet summarizes the information in the RED for
warfarin and its sodium salt.
Warfarin Warfarin and its sodium salt are registered for use in controlling
commensal rodents (rats and mice) in and around homes, animal and
agricultural premises, and commercial and industrial sites. Warfarin is
a blood anticoagulant; its sodium salt is used medically to treat people
with blood hypercoagulation problems. These compounds used as
rodenticides cause internal bleeding and hemorrhaging which
ultimately is fatal in rats and mice. They are applied as dry and liquid
baits, and as a dust which acts as a tracking powder. All uses of
warfarin and its sodium salt are eligible for reregistration.
Regulatory
History
Warfarin and its sodium salt were first Federally registered for
use in the United States as rodenticides in 1952. EPA issued a
Registration Standard for these pesticides in August 1981, and required
certain additional data. In April 1989, after reviewing the studies
submitted, the Agency issued a "Draft Warfarin Reregistration
Document" for public comment. Rather than issue a final version of
that document, EPA has developed the RED on warfarin and its
sodium salt.
Cv6 Printed on Recycled Paper
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Health All of EPA's toxicology data requirements for warfarin and its
Effects sodium salt have been satisfied. Because a great deal of information
about warfarin's effects on people is available, animal toxicity studies
were not needed or required.
Warfarin's toxicology and mechanism of action, as well as the
methods for treating warfarin overdose in humans, are well
understood. A synthetic analogue of Vitamin K, warfarin is a member
of the coumarin family of blood anticoagulant chemicals. Its sodium
salt has been used by doctors for years in treating people with
hypercoagulation problems.
Because of its high degree of acute oral toxicity, technical
warfarin has been placed in Toxicity Category I (the most toxic
category). However, the dermal and inhalation toxicity of warfarin are
not significant. Warfarin does not cause allergic or sensitization
problems in people exposed to it orally or through injections.
Warfarin has been established clearly as a human teratogen, as it
causes birth defects in the offspring of women receiving clinical doses
of the compound during any trimester of pregnancy. (However, the
amount of warfarin contained in the rodenticide bait products
registered for use by homeowners is very low. A single ingestion of
warfarin-treated bait by an adult female would not be likely to cause
teratogenic effects.)
Routes
Of Exposure
Through the Diet
Historically, none of warfarin's rodenticide uses were considered
food or feed uses, so residue chemistry data were not required and
tolerances (legal residue limits) or exemptions from the requirement of
a tolerance were not established. Similarly, no international Codex
Maximum Residue Levels were set.
More recently, EPA has decided that the use of warfarin tracking
powder formulations in food and feed handling establishments has the
potential to contaminate food and feed. Therefore, warfarin tracking
powder products will have to bear new label language that limits the
placement of tracking powder to inaccessible areas within such
establishments. If this new label language is not adopted, residue
chemistry data will be required and warfarin tolerances may have to be
established.
During Application
Warfarin's use patterns do not trigger data requirements for
applicator or reentry exposure studies.
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Incidents
Poison control centers report thousands of incidents or suspected
incidents of human exposure to anticoagulant rodenticides each year.
However, accidental ingestion of warfarin seldom results in life-
threatening or disabling symptoms. Pet exposure incidents also are
reported (most involving dogs), and deaths occur in some of these
animal exposure incidents.
These human and pet poisoning incidents point to the need for
use of tamper-resistant bait stations when warfarin baits are applied in
areas accessible to children and nontarget animals, as required by
current product labeling.
Environmental All the previously required studies needed to assess the
Hazards environmental impact of warfarin and its sodium salt have been
submitted to EPA and found acceptable, except two fish toxicity studies
and one invertebrate toxicity study using the sodium salt. However,
while these studies are being required, warfarin's sodium salt is eligible
for reregistration, since its use in and around buildings is expected to
result in little exposure to fish and aquatic invertebrates.
Environmental Fate
The environmental fate data requirements for warfarin and its
sodium salt were waived. Based on the use patterns and label
recommendations of warfarin rodenticide products, significant residues
of concern are not expected to be introduced into the environment.
Ecological Effects
Information available to EPA on the acute avian toxicity of
warfarin indicates that the pesticide is practically nontoxic to game
birds. In subacute studies, warfarin is moderately toxic to practically
nontoxic to upland game birds and waterfowl. Since use of warfarin
and its sodium salt according to label directions and restrictions would
not result in significant exposure of wild avian species, no additional
avian testing is required.
Certain questions about the toxicity of warfarin to fish remain.
However, EPA is not requiring a repeat of the aquatic toxicity studies
already available because of warfarin's nonaquatic use pattern, its
insolubility, and long field experience showing no potential hazards to
aquatic organisms.
Studies are being required to assess the toxicity of the sodium salt
of warfarin to fish, since the sodium salt is more soluble in water than
warfarin. However, the sodium salt is eligible for reregistration even
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while these studies are being developed, since significant exposure to
fish is not expected to occur from currently registered uses.
The use of warfarin as a hand-placed bait limits the potential for
any secondary exposure of nontarget animals. However, because of its
high degree of mammalian toxicity and its use patterns, warfarin could
adversely affect endangered or threatened species. The need for
further requirements to protect endangered species will be explored in
a forthcoming, formal consultation between EPA and the U.S. Fish
and Wildlife Service.
Additional Data
Required
The generic data base for warfarin has been reviewed and found
to *>e substantially complete. Certain product chemistry studies must
be replaced. Three acute toxicity tests on fish and aquatic
invertebrates must be submitted to complete a risk assessment for the
sodium salt.
Product Labeling
Changes Required
The labels of end-use products containing warfarin and its sodium
must bear the following types of use directions and precautions.
Please see the RED itself for the exact language of this and other
required labeling:
* The Restricted Use Pesticide classification still applies to, and
must appear on, tracking powder products;
* A statement regarding teratogenicity, warning of warfarin's
potential to cause birth defects, must be added to tracking powder
products and concentrates used to prepare dry baits;
* To prevent contamination of food and feed, tracking powder
products intended for use in food/feed handling establishments must
limit placement of powder to concealed, inaccessible places.
* To protect children and nontarget animals, tracking powder
products must bear a strong precautionary statement and new
restrictions limiting placement of powder to locations not accessible to
children, pets, domestic animals or nontarget wildlife;
* To protect children and nontarget animals, bait products must
require use of tamper-resistant bait stations.
Regulatory
Conclusion
* All registered rodenticides containing warfarin or its sodium
sa't can be used without causing unreasonable adverse effects in people
or the environment. Therefore, all pesticide products containing
warfarin or its sodium salt as the sole active ingredient are eligible for
reregistration.
* EPA is requiring product chemistry data on warfarin to replace
unacceptable studies, as well as fish and aquatic invertebrate data on
the sodium salt, to complete a risk assessment. Due to its limited use
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pattern, however, the sodium salt is eligible for reregistration while
these studies are being developed.
* Pesticide tracking powder uses in food and feed handling
establishments are now considered to be food uses. Therefore, to be
eligible for reregistration, warfarin products must bear new label
language limiting placement of tracking powder to inaccessible areas
within such establishments.
* An endangered species consultation is being initiated to
determine whether any special protective measures are needed.
* EPA will reregister individual products containing warfarin or
its sodium salt once the appropriate generic data, product specific data
and revised product labeling are submitted to and accepted by the
Agency.
For More EPA is requesting public comments on the Reregistration
Information Eligibility Document for warfarin and its sodium salt during a 60-day
time period, as announced in a Notice of Availability published in the
Federal Register. To obtain a copy of the RED or to submit written
comments, please contact the Public Response and Program Resources
Branch, Field Operations Division (H-7506C), Office of Pesticide
Programs, U.S. EPA, Washington, D.C. 20460, telephone 703-557-4436,
or Fax 703-557-1884. Please note that after the comment period
closes, the RED will be available from NTIS, at the address and
telephone number below.
To obtain a copy of the August 1981 Registration Standard for
warfarin and its sodium salt, please contact the National Technical
Information Service (NTIS), 5285 Port Royal Road, Springfield, VA.
22161, telephone 703-487-4650. Request document #PB82-140716.
For more information about warfarin and its sodium salt, or
about EPA's pesticide reregistration program, please contact the
Special Review and Reregistration Division (H-7508W), Office of
Pesticide Programs, U.S. EPA, Washington, D.C. 20460, telephone
703-808-8000, or Fax 703-308-8005.
For information about the health effects of pesticides, or for
assistance in recognizing and managing pesticide poisoning symptoms,
please contact the National Pesticides Telecommunications Network
(NPTN). Call toll-free 1-800-858-7378, 24 hours a day, seven days a
week, or Fax your inquiry to 806-743-3094.
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