United States
Environmental Protection
Agency
Pesticides And
Toxic Substances
(7508W)
738-F-91-111
June 1991
R.E.D. FACTS
Warfarin
Pesticide
Reregistration
Warfarin
Regulatory
History
All pesticides sold or used in the United States must be 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 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.
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.
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Health
Effects
Routes
Of Exposure
All of EPA's toxicology data requirements for warfarin and its 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.)
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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Environmental
Hazards
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.
All the previously required studies needed to assess the 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 The Seneric data base for warfarin has been reviewed and found to be
RedLJJred 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
Regulatory
Conclusion
The labels of end-use products containing warfarin and its sodium salt
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.
* All registered rodenticides containing warfarin or its sodium salt 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 MOTG EPA is requesting public comments on the Reregistration Eligibility
Information 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
(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 (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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