Docket Number: EPA

- HQ

- OPP

- 2011

- 0682 www.regulations.gov



## Tanol derivatives (furanone) Summary Document Registration Review : Initial Docket September 20 113 

### 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 Der ivatives )

. (DP Barcode: D 389815

, September 16 , 2011 ).

2. Furanone: Human Health Assessment Scoping Document in Support of Registration Review. (DP Barcode: D 392227, September 7, 2011)

.

3. Tanol dervatives: Review of Human Incidents (DP Barcode: D39355 4, 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 1 1, 2011)

. These and other supporting documents for the tanol derivatives (furanone) registration review case may be found in the docket EPA

- HQ

- OPP

- 201 1

- 0 682 at www.regulations.gov

.4 

### 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 ti me. 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/registr ation_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 contin ues 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 opportu nity 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
t anol 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 cosmeti c 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 ingredient s , h owever, the registration review only addresses the uses of the tanol derivative s 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 condu cted 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 assess ment, for the tanol derivatives (furanone).5 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 c onducted a n 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 d erivatives 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 critica l 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 Nor th 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

- 0 0293 (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 predictio ns, 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 chroni c risk estimates.

**•** Current tanol derivative labels are u nclear with respect to certain application parameters6 (such as a seasonal or yearly application limit), or specificity regarding application procedures (such as a descriptio n of application in a giv en 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 formula tion 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 tes t

o GLN 850.1300 Freshwater invertebrate

– life cycle test

**•** The Agency also encourages submission of other information that may inform its
est imate 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 com prehensive human health risk assessment for the tanol derivatives was conducted i n September , 199 5 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

a vailable human health effects informa tion comes from open literature and indicates that the tanol derivatives exhibit low toxicity to humans.7 **•** Based on the low e xposure 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 registra tion review of tanol derivatives.

**•** Please refer to the document: Furanone Human Health Assessment Scoping Document in Support of Registration Revie w, September 7, 2011

, in the registration review docket for

a more detailed discussion of the anticipated hum an 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, sub chronic 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 endo crine 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 t anol 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 base d 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 m ust 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 a mong 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 future8 EDSP orders/data call

- ins, requiring the submission of EDSP screening assays for the ta nol derivatives

. For further informati on 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. Da ta S ubmission 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 D ecis ion 2016

– Oct.

– Dec. Close Public C omment P eriod 2017

– Jan.

– March Registration Review D ecision and Begin P ost

- D ecision F ollow

- up 2017 Total ( years ) 6

The public is invited t o 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 Irritants9 The ta nol 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, n o Total Maximum Daily Load s (TMDL) have been developed for the tanol derivatives 2 . More inform ation on impaired water bodies and TMDLs can be found at the Agency’s website 3

. The Agency invites submission of water quality data for th is 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 Process 4 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, reg ulations, 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, unusuall y 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. Envi ronmental Justice

Stakehold ers are also specifically asked to provide information and data that will assist the Agency in refining the risk assessment s , 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=PEST ICIDES
3 http://www.epa.gov/owow/tmdl/
4 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm10 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:11 II. FACT SHEET

**•** Tanol derivatives (furanone): Background Information :

o G amma

- Nonalactone : PC Code

- 122301; CAS# 104

- 61

- 0

o G amma

- 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 Divis ion 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 a s a repellant s 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 granu lar 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 t anol 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 exceeda nces 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 Fo rmulation 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 regi stration review docket for a12 detailed summary of the key findings of the most recent human health assessment . A summary follows:

Ha z ard Characterization :

**•** No target organ, mode of action, or cancer effects have been identified with the tanol derivatives i n 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 D rinking 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 tan ol 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 ha ve a c ommon 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 h ave a common mechanism of toxicity with other substances and a cumulative risk a ssessment 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.13 **•** 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 Inte rnational 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 Novem ber 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 Sy s tem (PPLS) website: :

http://oaspub.epa.gov /pestlabl/ppls.home . A summary of f uranone 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(3 H)

- 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