Docket Number: EPA-HQ-OPP-2011-0682

www.regulations.gov

Tanol derivatives (furanone) Summary Document 

Registration Review: Initial Docket

September 2011

3

TABLE OF CONTENTS

Page 

I. Preliminary Work Plan (PWP) 4

II. Fact Sheet 10

________________________________________________

Please Note

This Preliminary Work Plan and Fact Sheet summarize the Environmental Protection Agency's 

current understanding of, and anticipated actions for the registration review of the tanol 

derivatives based on the following documents:

1. Registration Review: Problem Formulation for Ecological Risk and Endangered Species 

Assessments for Dihydro-5-pentyl-2(3H)-furanone and Dihydro-5-heptyl-2(3H)-furanone 

(Furanones/Tanol Derivatives). (DP Barcode: D389815, September 16, 2011).

2. Furanone: Human Health Assessment Scoping Document in Support of Registration 

Review. (DP Barcode: D392227, September 7, 2011).

3. Tanol dervatives: Review of Human Incidents (DP Barcode: D393554, September 7, 

2011).

4. BEAD Chemical Profile for Registration Review: Tanol Derivatives (Chemical Code #s 

122301 and 122302). (April 7, 2011).

5. PRD Appendix A: Food/Feed & Non-Food/Non-Feed Uses Considered in Registration 

Review Planning. (March 11, 2011).

These and other supporting documents for the tanol derivatives (furanone) registration review 

case may be found in the docket EPA-HQ-OPP-2011-0682 at www.regulations.gov. 
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I. Preliminary Work Plan

The Food Quality Protection Act of 1996 (FQPA) 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 reevaluates pesticides to make sure that as change occurs, 

products in the marketplace can be used safely. Information on this program is provided at: 

Introduction:

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

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 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 and commit to a final work plan and schedule for the registration review of the 

tanol derivatives (dihydro-5-pentyl-2(3H)-furanone and dihydro-5-heptyl-2(3H)-furanone), 

which are also sometimes referred to by their common name, “furanone”. 

The tanol derivatives are naturally occurring lactones (cyclic esters) found in apricots, peaches, 

meat and milk. They have been approved as a food additive (by the Food and Drug Association 

(FDA)) and for use in cosmetic products (such as lotions, detergents, and perfumes). All tanol 

derivative pesticide products are co-formulated with d-limonene (registration review case 3083). 

The tanol derivatives are botanical derivatives registered for use as a repellant to cats, dogs and 

mosquitoes. The tanol derivatives are registered as an active component in two products. The 

tanols are also used in other pesticide products as inert ingredients, however, the registration 

review only addresses the uses of the tanol derivatives where it is considered an active 

component. They were first registered in 1983 as a cat repellent. The furanone reregistration 

eligibility decision (RED) was completed in June of 1996, and no tolerance reassessment 

eligibility decision (TRED) was conducted because there are no food uses and, therefore, no 

associated tolerances. 

Anticipated Risk Assessment and Data Needs:

During registration review the Agency anticipates conducting an ecological risk assessment, 

including an endangered species assessment, for the tanol derivatives (furanone). 
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Ecological Risk:

• The most recent comprehensive ecological risk assessment for the tanol derivatives was 

completed in April 1996, to support the 1996 Reregistration Eligibility Decision.

• The Agency has not conducted an ecological risk assessment that supports a complete 

endangered species determination for the tanol derivatives. The ecological risk 

assessment planned during registration review will allow the Agency to determine 

whether the use of the tanol derivatives has “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 (FWS) and/or National Marine Fisheries Service (NMFS) (the Services), as

appropriate.

• On January 19, 2011, the Center for Biological Diversity and the Pesticide Action 

Network North America filed a lawsuit in the United States District Court for the 

Northern District of California, against the Environmental Protection Agency (EPA) for 

allegedly failing to undergo consultation with the United States Fish and Wildlife Service 

and the National Marine Fisheries Service regarding the effects of over 350 pesticides, 

including the tanol derivatives, on over 200 endangered and threatened species 

throughout the United States (Center for Biological Diversity, et al. v. EPA, et al., No. C 

11-00293 (N.D.Cal.)).

• The environmental fate, effects and ecological database on the tanol derivatives is

incomplete.

• In the absence of data on the fate of the tanol derivatives, the Agency may address

uncertainties with available structure-based predictions, or with conservative 

assumptions. However, given the structure of the tanol derivatives, the Agency may be 

able to avoid using conservative assumptions regarding the environmental fate with data 

on aerobic soil metabolism and aqueous hydrolysis. 

• In the absence of ecological effects data, the Agency may rely upon conservative 

assumptions involving data on formulated products, any available structure-based 

predictions, or conservative assumptions when either going across species, or when 

extrapolating estimated chronic effects endpoints from available acute effects endpoints. 

Certain data on the chronic effects of the tanol derivatives for aquatic and avian species

may remove the Agency’s need to employ conservative assumptions when developing 

chronic risk estimates. 

• Current tanol derivative labels are unclear with respect to certain application parameters 
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(such as a seasonal or yearly application limit), or specificity regarding application 

procedures (such as a description of application in a given band width). In the absence of 

clear label language that provides information on efficacious usage and use limitations, 

the Agency must employ conservative assumptions to complete the ecological exposure

assessment. Please refer to the problem formulation for a discussion of uncertainties on 

tanol derivative products.

• Based on the use and ecological fate and effects data base for the tanol derivatives, the 

Agency anticipates requiring the following data. 

o GLN 835.4100 Aerobic Soil Metabolism

o GLN 835.2120 Hydrolysis 

o GLN 850.2300 Avian reproduction

o GLN 850.1400 Freshwater fish – early life stage test 

o GLN 850.1300 Freshwater invertebrate – life cycle test

• The Agency also encourages submission of other information that may inform its 

estimate of potential ecological exposure, such as updated total product production 

information.

• Please refer to the document: Registration Review: Problem Formulation for Ecological 

Risk and Endangered Species Assessments for Dihydro-5-pentyl-2(3H)-furanone and 

Dihydro-5-heptyl-2(3H)-furanone (Furanones/Tanol Derivatives), September 16, 2011, 

in the registration review docket for a more detailed discussion of the anticipated 

ecological risk assessment and data needs.

Human Health Risk:

• The most recent comprehensive human health risk assessment for the tanol derivatives 

was conducted in September, 1995 to support the 1996 Reregistration Eligibility 

Decision.

• Based on the registered uses of the tanol derivatives, human exposure is expected to be 

minimal. 

• The human health toxicity database for the tanol derivatives is incomplete. Most of the 

available human health effects information comes from open literature and indicates that 

the tanol derivatives exhibit low toxicity to humans. 
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• Based on the low exposure and low human health toxicity associated with the tanol 

derivatives, the Agency does not anticipate requiring data or conducting a new 

comprehensive human health risk assessment (including dietary, residential, and/or 

occupational) for the registration review of tanol derivatives.

• Please refer to the document: Furanone Human Health Assessment Scoping Document in 

Support of Registration Review, September 7, 2011, in the registration review docket for 

a more detailed discussion of the anticipated human health risk assessment and data 

needs.

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 reregistration decision for the tanol derivatives, 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), the tanol 

derivatives (furanone) are subject to the endocrine screening part of the Endocrine Disruptor 

Screening Program (EDSP). 

Endocrine Disruptor Screening Program:

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. The tanol 

derivatives were not among the group of 58 pesticide active ingredients on the initial list to be 

screened under the EDSP. Accordingly, as part of registration review, EPA will issue future 
8

EDSP orders/data call-ins, requiring the submission of EDSP screening assays for the tanol 

derivatives. For further information on the status of the EDSP, the policies and procedures, the 

list of 67 chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit 

our website: http://www.epa.gov/endo/.

EPA has created the following estimated timeline for the completion of the registration review of 

the tanol derivatives. 

Timeline:

Registration Review for Tanol derivatives 

Projected Registration Review Timeline

Activities Estimated Date

Opening the docket

Open Public Comment Period for the Furanone Docket 2011 – September

Close Public Comment Period 2011 – November

Case Development

Develop Final Work Plan (FWP) 2012 – January

Issue DCI 2012 – Oct. – Dec. 

Data Submission 2014 – Oct. – Dec. 

Open Public Comment Period for Preliminary Risk Assessments 2016 – Apr. – June 

Close Public Comment Period 2016 – July – Sept.

Registration Review Decision

Open Public Comment Period for Proposed Reg. Review Decision 2016 – Oct. – Dec. 

Close Public Comment Period 2017 – Jan. – March

Registration Review Decision and Begin Post-Decision Follow-up 2017

 Total (years) 6

The public is invited to comment on EPA’s preliminary work plan and rationale. The Agency 

will carefully consider all comments as well as any additional information or data provided in a 

timely manner prior to issuing a final work plan for the tanol derivatives (furanone) case.

Guidance for Commenters:

Through the registration review process, the Agency intends to solicit information on trade 

irritants and, to the extent feasible, take steps toward facilitating irritant resolution. Growers and 

other stakeholders are asked to comment on any trade irritant issues resulting from lack of 

Maximum Residue Limits (MRLs) or disparities between U.S. tolerances and MRLs in key 

export markets, providing as much specificity as possible regarding the nature of the concern. 

Trade Irritants
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The tanol derivatives are not identified as a cause of impairment for any water bodies listed as 

impaired under section 303(d) of the Clean Water Act

Water Quality

1

. In addition, no Total Maximum Daily 

Loads (TMDL) have been developed for the tanol derivatives2. More information on impaired 

water bodies and TMDLs can be found at the Agency’s website3. 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 Process4 in order to ensure they can be used quantitatively or qualitatively in 

pesticide risk assessments.

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 many 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 the tanol derivatives (furanone), 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.

Environmental Justice

Stakeholders are also specifically asked to provide information and data that will assist the 

Agency in refining the risk assessments, including any species-specific ecological effects 

determinations. The Agency is interested in receiving the following information: 

Other Information

1. use or potential use distribution (e.g., acreage and geographical distribution of furanone 

applications)

2. suggestions from stakeholders on ways to reduce non-target organism exposures to the 

tanol derivatives.

3. use history

4. directly acquired county-level usage data (not derived from state level data)

a. total pounds per year (county level)

b. maximum reported use rate (lbs. a.i./acre) from usage data – county

c. the year the pesticide was last used in the county/sub-county area

d. the years in which the pesticide was applied in the county/sub-county area

5. typical interval (days)

6. state or local use restrictions

 

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

2 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant_group_name=PESTICIDES 3 http://www.epa.gov/owow/tmdl/

4 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm
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7. ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian, insect 

(e.g., honey bees) and mammalian mortalities) not already reported to the Agency.

8. monitoring data

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

received in a timely manner, and then issue a Final Work Plan for the tanol derivatives

registration review case.

Next Steps:
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II. FACT SHEET

• Tanol derivatives (furanone):

Background Information:

o Gamma-Nonalactone: PC Code - 122301; CAS# 104-61-0 

o Gamma- Undecalactone: PC Code - 122302; CAS# 104-67-6

• The Reregistration Eligibility Decision was completed in 1996. 

• There are 2 active FIFRA Section 3 product registrations for furanone: both are end-use 

products. 

• The tanol derivatives (furanone) are naturally occurring botanical lactones which are 

registered for use as an insect, dog and cat repellent.

• The Pesticide Re-evaluation Division Chemical Review Manager (CRM) is James 

Parker: parker.james@epa.gov.

• Product Manager (PM) is Richard Gebkin: gebkin.richard@epa.gov.

Use & Usage Information:

• Products containing the tanol derivatives are registered for use as a repellants and are

registered for use on outdoor residential areas (to repell dogs and cats) and impregnated 

wrist & ankle bands (to repel mosquitos). 

 

• When used in residential areas, the tanol derivatives are formulated as a granular and 

sprinkled/applied to specific areas in order to discourage dogs and cats from defecating in 

those areas. 

• Non-pesticidal uses include use as food and cosmetic additive. 

• There are no pending or recent actions associated with the tanol derivatives.

Recent Actions:

Ecological Risk Assessment Status

• In the most recent ecological risk assessment (1995), the Agency’s level of concern 

(LOC) was not exceeded for non-target birds, mammals, or freshwater fish. The Agency 

identified (slight) risk exceedances to freshwater invertebrates based on data on the 

formulated product. Risks were also assumed for non-target plants, and estuarine/marine 

fish and invertebrates, based on the lack of data.

:

• Please refer to the document: Registration Review: Problem Formulation for Ecological 

Risk and Endangered Species Assessments for Dihydro-5-pentyl-2(3H)-furanone and 

Dihydro-5-heptyl-2(3H)-furanone (Furanones/Tanol Derivatives), September 16, 2011,

in the registration review docket for a detailed summary of the key findings of the most 

recent environmental fate and effects assessment. 

Human Health Risk Assessment Status:

Please refer to the document: Furanone Human Health Assessment Scoping Document in 

Support of Registration Review, September 7, 2011 in the registration review docket for a 
12

detailed summary of the key findings of the most recent human health assessment. A summary 

follows:

Hazard Characterization:

• No target organ, mode of action, or cancer effects have been identified with the tanol 

derivatives in the toxicity data available through open literature.

• The tanol derivatives are categorized as Toxicity Category IV via the oral, dermal and 

inhalation routes. It is neither a skin (nor eye) irritant based on acute toxicity studies.

Dietary (Food and Drinking Water):

• Neither an acute nor a chronic dietary assessment has been conducted on the tanol 

derivatives because no toxicity endpoint(s) have been identified in the available toxicity 

data.

• No drinking water assessment has been conducted for the tanol derivatives.

Residential and Occupational:

• Neither residential nor occupational exposure was previously quantitatively assessed for 

either active or inert uses of the tanol derivatives.

Aggregate:

• Since the Agency has not identified any toxicological endpoints appropriate for a quantitative 

[aggregate] risk assessment (dietary, or residential), an aggregate assessment has not been 

conducted.

Cumulative:

• EPA does not have, at this time, available data to determine whether the tanol derivatives

have a common mechanism of toxicity with other substances or how to include this 

pesticide in a cumulative risk assessment. Therefore, EPA has not assumed that the tanol 

derivatives have a common mechanism of toxicity with other substances and a 

cumulative risk assessment is not anticipated at this time.

Incident Reports:

• The Agency’s Aggregate Incident Database System (IDS) identified 116 low severity 

(minor, unknown or no effects) incidents associated with human incidents involving the 

tanol derivatives. The main IDS database also contained 10 tanol derivative incident 

cases, none of which involved the single chemical furanone only. The tanol derivatives

are not included in the Agricultural Health Study (AHS) and therefore no AHS report was 

conducted. Based on the low exposure, frequency and severity of the reported incidents, 

there does not appear to be reason to warrant further investigation of furanone at this 

time.
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• Preliminary reviews of the Ecological Incident Information System (EIIS, version 2.1) 

and the Avian Incident Monitoring System (AIMS)5 were conducted on June 23, 2011 for 

the furanones, as well as limonene. There were no avian incidents reported in the AIMS 

database. There are no incidents reported in the EIIS database. 

Tolerances and International Harmonization:

• Tolerances are not established for the tanol derivatives because it is not registered for use 

on any food commodities.

 

• The most recent data call-in on the tanol derivatives was issued by the Agency in 

November 1998. The registrant has submitted data to satisfy the requirements of that 

notice.

Data Call-In Status:

Labels

• Furanone labels can be obtained from the Pesticide Label System (PPLS) website: 

:

http://oaspub.epa.gov/pestlabl/ppls.home. A summary of furanone labels is provided in 

the table below.

Furanone Products

Registration

Number

Product Name Active 

Ingredient

45987-1 DOO-NOT DOG & CAT REPELLENT 2(3H)-Furanone, dihydro-5-

pentyl-

.024%

5-Heptyldihydro-2(3H)-

furanone

.049%

66617-1 ISLAND MARKETING’S BUGCHASER 

BRAND INSECT REPELLENT 

WRISTBAND

2(3H)-Furanone, dihydro-5-

pentyl- .024%

5-Heptyldihydro-2(3H)-

furanone

.049%

 

5 http://www.abcbirds.org/abcprograms/policy/pesticides/aims/aims/index.cfm