3

4. BEAD Chemical Profile (BCP) for Registration Review: Warfarin and Warfarin Sodium 

Salts (086002 and 086003) Amended. Colwell Cook. 10/14/2015.

5. Warfarin (086002) EFED Table 1 Report. 01/14/2015. 

6. Warfarin (086002) HED Master Label Report. 01/14/2015. 

7. Warfarin LUIS Report – EFED Label Date Report 1-14-15. 01/14/2015. 

8. Warfarin (086002) General Chemical (Issues) Report. 01/14/2015. 

These and other supporting documents for the warfarin and warfarin sodium salt registration 

review case may be found in the docket EPA-HQ-OPP-2015-0481 at 

http://www.regulations.gov. 
4

OVERVIEW 

The docket for warfarin and warfarin sodium salt is now open, initiating the first public comment 

period for this registration review (docket number EPA-HQ-OPP-2015-0481). This registration 

review case includes the following active ingredients: warfarin (086002) and warfarin sodium 

salt (086003). Warfarin and its sodium salt are anticoagulant rodenticides. They interfere with 

vitamin K synthesis, a vital component in the blood clotting pathway, thereby causing 

hemorrhaging in rodents. Warfarin and warfarin sodium salt were registered in 1950 and 1954, 

respectively, however there are currently no active registrations for warfarin sodium salt. 

Warfarin was the first anticoagulant rodenticide to be developed and thus is considered a “firstgeneration” rodenticide. Warfarin is used to control mice, rats, voles and moles in and around 

homes and buildings, agricultural and animal premises, commercial and industrial sites, transport 

vehicles and sewage systems. 

This Preliminary Work Plan (PWP) document explains what EPA's Office of Pesticide Programs 

knows about warfarin, highlights anticipated data and assessment needs, identifies the types of 

information that would be especially useful to the Agency in conducting the review, and 

provides an anticipated timeline for completing the registration review for warfarin. 

 

The registration review process was designed to include a public participation component to 

solicit input from interested stakeholders. The Agency intends, by sharing this information in the 

docket, to inform the public of what it knows about warfarin and what types of new data or other 

information would be helpful for the Agency to receive as it moves toward a decision on 

warfarin. The Agency encourages all interested stakeholders to review the PWP and Appendix, 

and to provide comments and additional information that will help the Agency’s decisionmaking process for this chemical. In addition to general areas on which persons may wish to 

comment, there are some areas identified in the PWP and Appendix about which the Agency is 

specifically seeking comments and information. Interested stakeholders could include: 

environmental non-profit or interest groups; pesticide manufacturers; agricultural labor or 

commodity groups; commercial, institutional, residential, and other users of pesticides; or the 

public at large. 

The PWP begins by listing the anticipated data needs for warfarin and warfarin sodium salt. 

Next, it discusses the statutory and regulatory authority for registration review. Then the 

document provides chemical facts, use and usage information, recent actions, the anticipated risk 

assessments, and a projected registration review timeline for warfarin and warfarin sodium salt. 

Finally, the Appendix to this document includes identification and discussion of some areas that 

are considered generally in registration review along with some additional chemical case-specific 

information. 

A registration Standard for warfarin and its sodium salt was issued in August 1981. The 

Registration Standard summarized the available data supporting the registration of warfarin and 

its sodium salt and required additional data. Pursuant to FIFRA section 4(g) (2) (A), the Agency 

issued the Reregistration Eligibility Document for Warfarin and its Sodium Salt in May 

1991. The Agency is now initiating the Registration Review of Warfarin and its Sodium 

Salt. With this initial docket opening for the warfarin registration review, the Agency is also 

publishing an ecological problem formulation for warfarin entitled, Registration Review – 
5

Preliminary Problem Formulation for Ecological Risk, Environmental Fate, and Drinking Water 

Assessments for Warfarin and a combined scoping document and qualitative human health risk 

assessment for warfarin entitled Warfarin and Warfarin Sodium Salt. Human Health Assessment 

Scoping Document and Draft Human Health Risk Assessment in Support of Registration Review. 

ANTICIPATED DATA NEEDS 

Table 1 below summarizes anticipated data needs for warfarin. For additional discussion of the 

anticipated data needs, see the Registration Review – Preliminary Problem Formulation for 

Ecological Risk, Environmental Fate, and Drinking Water Assessments for Warfarin and 

Warfarin and Warfarin Sodium Salt. Human Health Assessment Scoping Document and Draft 

Human Health Risk Assessment in Support of Registration Review available in the public docket 

EPA-HQ-OPP-2015-0481, accessible at http://www.regulations.gov.

Table 1: Anticipated Data Needs for the Warfarin Registration Review 

Guideline 

Number1 Study Title1 

Test Material 

Estimated 

Timeframe 

(Months from 

receipt of DCI) 

Anticipated Data Needs for the Parent Warfarin

850.6100 Environmental chemistry methods and associated 

independent laboratory validations for soil and 

water 

TGAI 12 

850.2100 Avian oral toxicity (with a passerine species) TGAI 12 

850.2300 Avian reproduction toxicity (with an upland 

game bird species and a waterfowl species) TGAI 24 

850.3100 Earthworm subchronic toxicity test TGAI 12 

 

1

 On June 27, 2012, EPA announced certain revisions in harmonized guideline series 850 – Ecological Effects Tests 

– including renumbering and other designations or changes for some guideline studies. See “Final Test 

Guidelines; OCSPP 850 Series; Notice of Availability” 77 FR 38282, June 27, 2012. 

http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0154-0028 
6

STATUTORY AND REGULATORY AUTHORITY 

The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program. All 

pesticides distributed or sold in the United States (U.S.) generally must be registered by the 

Environmental Protection Agency (EPA or the Agency), based on scientific data showing that 

they will not cause unreasonable risks to human health or the environment when used as directed 

on product labeling. The registration review program is intended to make sure that, as the ability 

to assess risk evolves and as policies and practices change, all registered pesticides continue to 

meet the statutory standard of no unreasonable adverse effects to human health or the 

environment. Changes in science, public policy, and pesticide use practices will occur over time. 

Through the registration review program, the Agency periodically re-evaluates pesticides to 

make sure that as change occurs, products in the marketplace can be used safely. Information on 

this program is provided on EPA’s website.2

The Agency is implementing the registration review program pursuant to Section 3(g) of the 

Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), and will review each registered 

pesticide every 15 years to determine whether it continues to meet the FIFRA standard for 

registration. The regulations governing registration review begin at 40 CFR 155.40. The 

Agency will consider benefits information and data as required by FIFRA. The public phase of 

registration review begins when the initial docket is opened for each case. The docket is the 

Agency’s opportunity to state what it knows about the pesticide and what additional risk analyses 

and data or information it believes are needed to make a registration review decision. After 

reviewing and responding to comments and data received in the docket during this initial 

comment period, the Agency will develop a Final Work Plan (FWP) and anticipated schedule for 

the registration review of warfarin. 

CHEMICAL FACTS 

Table 2 provides a summary of the chemical facts for warfarin. 

Table 2: Chemical Facts for Warfarin

PC code 086002 (warfarin) 086003 (warfarin sodium salt) 

Case Number 0011 

CAS Number 81-81-2 (warfarin) 129-06-6 (warfarin sodium salt) 

Year first registered 1950 (warfarin) 1954 (warfarin sodium salt) 

Pesticide Type Rodenticide 

Chemical class Coumarin Anti-Coagulant 

Reregistration Eligibility 

Decision (RED) 

1991 RED for Warfarin 

1998 RED Rodenticide Cluster 

Cumulative group EPA has not made a common mechanism of toxicity finding as to 

warfarin and any other substances and warfarin does not appear to 

produce a toxic metabolite produced by other substances. 

40 CFR Citation There are no established tolerances for warfarin or its sodium salt. 

 

2

 http://www.epa.gov/oppsrrd1/registration_review/ 
7

Table 2: Chemical Facts for Warfarin

Dual-use Warfarin and its sodium salt are registered for conventional 

pesticidal uses only and have no registered antimicrobial or 

biopesticidal uses. 

Non-pesticidal uses The sodium salt of warfarin is used as an anticoagulant in the 

medical treatment of individuals with hyper-coagulation 

problems. 

Pesticide Re-evaluation 

Division, Chemical 

Review Manager 

Caitlin Newcamp, newcamp.caitlin@epa.gov, 703-308-8043 

Registration Division, 

Product Manager 

Marianne Lewis, lewis.marianne@epa.gov, 703-305-0120 

USE AND USAGE INFORMATION 

Table 3 summarizes the use and usage information for warfarin. Please see the BEAD Chemical 

Profile for Registration Review: Warfarin and Warfarin Sodium Salts (086002 and 086003) 

Amended available in the public docket EPA-HQ-OPP-2015-0481, accessible at 

http://www.regulations.gov. 

Table 3: Warfarin Use and Usage Information

Use Sites As a pesticide warfarin is registered for use in controlling rodents 

such as mice, rats, voles and moles. Warfarin has both indoor and 

outdoor uses including in and surrounding homes, buildings, 

agricultural and animal premises, commercial/ industrial sites, 

transport vehicles, general and ornamental lawns and turf. In its 

capacity to control rodents, and the potential diseases they vector, 

warfarin is identified as a public health pesticide. 

Summary of Usage EPA has no available usage data for warfarin. 

Formulation Type(s) Formulated as granules, pellets/tablets, microencapsulated pellets 

and solution (gel). 

Application Method(s) Applied in bait stations, by hand, orasyringe is used to apply the 

gel formulation into active underground mole burrows 

Technical Registrant(s) Reckitt Benckiser LLC, Bell Laboratories Inc., Hacco Inc., 

DuPont Chemoswed, Scimetrics Ltd. 

No. of Registrations 23 FIFRA Section 3 Registrations 

Restricted Use No 

Guidance for Commenters: Additional areas of information requested for this registration 

review, and of particular interest to EPA, are described below. 
8

 The following information would improve the Agency’s ability to assess potential 

ecological impacts from warfarin and other anticoagulant rodenticides during registration 

review: 

o Acute, chronic and secondary toxicity data including data on retention of 

ingredients in liver, blood and other body tissues 

o Studies on metabolism and retention times on warfarin in rodents and non-target 

species 

o Information on the number and species of birds and non-target mammals 

frequenting baited areas and the likelihood of their finding and consuming bait or 

poisoned primary consumers in the various use areas 

o Methods to determine liver concentrations 

o Total body burdens of rodenticide that would corroborate death or even if such a 

cause-effect relationship is appropriate (e.g., “threshold of toxicity”) 

o The impacts of sub-lethal effects on reproduction and non-target mortality (e.g.,

clotting abnormalities, hemorrhaging, stress factors including environmental 

stressors such as adverse weather conditions food shortages, predation, etc.) 

o Information on bioaccumulation of repeated sub-lethal exposures to bait or 

poisoned rodents 

o Any additional reports of incidents 

o Additional toxicity data exploring mode-of-action for warfarin 

o Data on effects of long-term, low-dose exposure of warfarin on avian 

reproduction and survival, and data to assess toxicity of warfarin to terrestrial 

invertebrates 

 Confirmation of the following label information: sites of application; formulations; 

application methods and equipment; maximum application rates; frequency of 

application, application intervals, and maximum number of applications per season; and 

geographic limitations on use. 

o Additionally, many of the labels for warfarin do not specify the maximum number 

of applications that can be applied per year. Some labels are missing a single 

maximum application rate. 

 Use distribution (e.g., acreage and geographical distribution of relevant use sites). 

 Median and 90th percentile reported use rates (lbs. ai/A) from usage data – national, state, 

and county. 

 Use information by formulation, including typical amounts applied by use site, seasonally 

and annually; distances applied from buildings, amounts used in rural versus urban areas; 

use by Certified Applicators versus homeowners and other non-certified applicators 

 Typical application timing (date of first application and application intervals) – national, 

state, and county. 

 Usage/use information for non-agricultural uses. 

 Typical application interval (days). 

 State or local use restrictions. 

 Foreign technical registrants not listed above who supply technical warfarin to the U.S. 

market. 
9

RECENT ACTIONS 

 2011: An endangered species risk assessment was completed for San Francisco Bay 

Species. 

 2013: A Notice of Intent to Cancel was released which included warfarin-based products. 

The details of this notice can be found at EPA-HQ-OPP-2013-0049 at 

www.regulations.gov. 

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW 

The most recent ecological risk assessment was an endangered species risk assessment for San 

Francisco Bay Species. Completed in 2011. Findings and conclusions of all previous risk 

assessments are summarized in the Warfarin and Warfarin Sodium Salt. Human Health 

Assessment Scoping Document and Draft Human Health Risk Assessment in Support of 

Registration Review and Registration Review – Preliminary Problem Formulation for Ecological 

Risk, Environmental Fate, and Drinking Water Assessments for Warfarin. These and other 

supporting documents for warfarin can be found at EPA-HQ-OPP-2015-0481 at 

www.regulations.gov. 

For this action of opening the warfarin registration review, the Agency has completed a 

qualitative human health risk assessment for warfarin in conjunction with its human health 

scoping document for warfarin. The Agency determined that no additional (human toxicity or 

exposure) data are needed at this time and a qualitative risk assessment for warfarin was 

warranted based upon the negligible exposure potential, lack of toxicity endpoints. A summary 

of anticipated risk assessments for the warfarin and warfarin sodium salt registration review are 

below.
10

Table 4: Anticipated Risk Assessments for the Warfarin and Warfarin Sodium Salt 

Registration Review 

Type of Risk Assessment Conduct? Notes 

Ecological and Environmental Fate 

Comprehensive ecological 

(species to be assessed 

include terrestrial and aquatic 

organisms), including 

endangered species 

Y 

Incidents Will Check for 

Updates 

A summary of reported ecological incidents can be 

found in the Problem Formulation. 

Human Health 

Dietary 

Food N A qualitative dietary exposure was conducted (as part 

of this initial docket opening for warfarin and its 

sodium salt) because warfarin or its salt are not fooduse chemicals and end-use product packaging is 

expected to result in negligible dietary (food and/or 

drinking water) exposure. Drinking Water N 

Occupational 

Handlers (mixers, loaders, 

applicators) 

N A qualitative occupation handler and post-application 

assessment was conducted (as part of this initial 

docket opening) because occupational exposures are 

anticipated to be negligible due to product packaging 

as a closed system. 

Post-application N 

Residential 

Handlers N A qualitative residential exposure assessment was 

conducted (as part of this initial docket opening) 

because residential bait applications are applied in 

bait stations or required to be packaged in tamperresistant packaging if children, domestic pets or 

wildlife may access. Therefore, the currently 

registered uses of warfarin are not expected to pose 

significant residential handler or residential postapplication exposure. 

Post-application N 

Other 

Aggregate N Because neither a quantitave dietary or quantitative 

residential assessment was completed for warfarin, a 

quantitative aggregate assessment for warfarin is not 

required at this time. 
11

TIMELINE 

EPA has created the following estimated timeline for the completion of the warfarin and warfarin 

sodium salt registration review in Table 5 below. 

Table 5: Projected Warfarin and Warfarin Sodium Salt Registration Review Timeline

Activities Estimated Date

Opening the Docket 

Open Docket and 60-day Public Comment Period 2015 December 

Close Public Comment 2016 February 

Case Development 

Final Work Plan 2016 May 

Issue DCI 2016 July - September 

Data Submission 2018 July - September 

60-day Public Comment Period for Draft Risk 

Assessments3

2020 January - March 

Registration Review Decision 

60-day Public Comment Period for Proposed 

Registration Review Decision 

2020 October - December 

Registration Review Decision and Begin Post-Decision 

Follow-up 

2021 

Total (years) 6 

NEXT STEPS 

After the 60-day public comment period closes, the Agency will review and respond to any 

comments received in a timely manner and then issue a FWP for the registration review of 

warfarin and warfarin sodium salt. 

 

3

 The regulations governing Registration Review generally require the Agency to provide a public comment period 

of at least 30 calendar days for draft risk assessments; see 40 CFR Part 155.53(c). For conventional pesticides, the 

Agency plans to provide a 60 calendar day public comment period generally for draft risk assessments. 

Cumulative N EPA has not made a common mechanism of toxicity 

finding as to warfarin and any other substances and 

warfarin does not appear to produce a toxic 

metabolite produced by other substances. 

Tolerances N Because warfarin is not a food-use chemical, there are 

no U.S. tolerances established 

Incidents Will Check for 

Updates 

For a discussion of reported incidents, see the 

Warfarin and Warfarin Sodium Salt. Human Health 

Assessment Scoping Document and Draft Human 

Health Risk Assessment in Support of Registration 

Review and Rodenticide: Tier I (Scoping) Review of 

Human Incidents and Epidemiology Assessment. 
12

Appendix – Additional Areas Considered in the Warfarin Registration Review 

PUBLIC COMMENTS AND FEEDBACK: 

Guidance for Commenters: The areas below highlight topics of special interest to the Agency 

where your comments, data submissions, or reference to sources of additional information could 

be of particular use.

Water Quality: 

Warfarin and warfarin sodium salt are not identified as a cause of impairment for any water 

bodies listed as impaired under section 303(d) of the Clean Water Act.4

 In addition, no Total 

Maximum Daily Loads (TMDL) have been developed for warfarin or its sodium salt.5 More 

information on impaired water bodies and TMDLs can be found at the Agency’s website.6 The 

Agency invites submission of water quality data for this pesticide. To the extent possible, 

data should conform to the quality standards in Appendix A of the OPP Standard Operating 

Procedure: Inclusion of Impaired Water Body and Other Water Quality Data in OPP’s 

Registration Review Risk Assessment and Management Process7 in order to ensure they can be 

used quantitatively or qualitatively in pesticide risk assessments. 

Environmental Justice: 

EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all 

people, regardless of race, color, national origin, or income, in the development, implementation, 

and enforcement of environmental laws, regulations, and policies. To help address potential 

environmental justice issues, the Agency seeks information on any groups or segments of the 

population who, as a result of their location, cultural practices, or other factors, may have 

atypical, unusually high exposure to warfarin or its sodium salt compared to the general 

population. Please comment if you are aware of any sub-populations that may have 

atypical, unusually high exposure compared to the general population.

ENDANGERED SPECIES: 

A risk assessment that supports a complete endangered species determination has not been 

conducted for warfarin or its sodium salt. The ecological risk assessment planned during 

registration review will allow the Agency to determine whether use of warfarin or its sodium salt 

has a “no effect” or “may affect” federally listed threatened or endangered species (listed 

species) or their designated critical habitats. When an assessment concludes that a pesticide’s 

use “may affect” a listed species or its designated critical habitat, the Agency will consult with 

the U.S. Fish and Wildlife Service and/or National Marine Fisheries Service (the Services), as 

appropriate. 

 

4 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885

5

http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant_

group_name=PESTICIDES 6 http://www.epa.gov/owow/tmdl/

7 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm
13

A previous endangered species assessment was conducted for the San Francisco Bay Species in 

2011 to address potential risk to the salt marsh harvest mouse and the Alameda whipsnake. 

Based on the best available information at the time of the risk assessment, the Agency made a 

“May Affect and Likely to Adversely Affect” determination for the two species from the use of 

warfarin or its sodium salt. The Agency also determined that there is the potential for effects to 

the Alameda whipsnake designated critical habitat from the use of warfarin. 

ENDOCRINE DISRUPTOR SCREENING PROGRAM: 

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of its most recent registration decision for warfarin and warfarin 

sodium salt, EPA reviewed these data and selected the most sensitive endpoints for relevant risk 

assessment scenarios from the existing hazard database. However, as required by FFDCA 

section 408(p), warfarin and its sodium salt are subject to the endocrine screening part of the 

Endocrine Disruptor Screening Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list 

of chemicals identified for EDSP screening was published on June 14, 20138

 and includes some 

pesticides scheduled for registration review and chemicals found in water. Neither of these lists 

should be construed as a list of known or likely endocrine disruptors. Warfarin is not included on 

either list. 

 

8

 See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of 

chemicals.