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Problem Formulation for the Ecological Risk and 

Endangered Species in Support of the Registration 

Review of Dihydro-5-pentyl-2(3H)-furanone and 

Dihydro-5-heptyl-2(3H)-furanone (Furanones/Tanol 

Derivatives)

Dihydro-5-pentyl-2(3H)-furanone

Dihydro-5-heptyl-2(3H)-furanone

CAS Registry Numbers: 000104-61-0, 000104-67-6

PC Codes: 122301, 122302

Authors:

Anita Ullagaddi, Biologist

Robert Miller, Environmental Scientist

Edward Odenkirchen, Senior Advisor

U. S. Environmental Protection Agency

Office of Pesticide Programs

Environmental Fate and Effects Division

Environmental Risk Branch I

1200 Pennsylvania Ave., NW

Mail Code 7507P

Washington, DC 20460

Reviewers:

Sujatha Sankula, Lead Biologist

Faruque Khan, Senior Fate Scientist

Nancy Andrews, Branch Chief

September 16, 2011
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Table of Contents

1. Purpose....................................................................................................................................... 4

2. Problem Formulation ................................................................................................................. 4

2.1. Nature of Regulatory Action............................................................................................... 4

2.2. Previous Assessments......................................................................................................... 5

2.2.1. Ecological Risk Assessments....................................................................................... 5

2.2.2. Drinking Water Exposure Assessments....................................................................... 5

3. Stressor Source and Distribution ............................................................................................... 5

3.1. Mode of Action................................................................................................................... 5

3.2. Overview of Pesticide Use and Usage ................................................................................ 6

3.3. Environmental Fate and Transport...................................................................................... 7

4. Receptors.................................................................................................................................... 7

4.1. Effects to Aquatic Organisms............................................................................................. 8

4.2. Effects to Terrestrial Organisms......................................................................................... 9

4.3. Incident Databases Review............................................................................................... 11

4.4. Ecosystems Potentially at Risk ......................................................................................... 11

5. Assessment Endpoints ............................................................................................................. 12

6. Conceptual Model.................................................................................................................... 12

6.1. Risk Hypothesis................................................................................................................ 12

6.2. Conceptual Diagram ......................................................................................................... 12

7. Analysis Plan ........................................................................................................................... 15

7.1. Stressors of Concern ......................................................................................................... 16

7.2. Measures of Exposure....................................................................................................... 16

7.3. Measures of Effect ............................................................................................................ 17

7.4. Integration of Exposure and Effects ................................................................................. 18

7.5. Deterministic and Probabilistic Assessment Methods...................................................... 18

7.6. Endangered Species Assessment ...................................................................................... 18

7.7. Drinking Water Assessment ............................................................................................. 19

7.8. Preliminary Identification of Data Gaps........................................................................... 19

7.8.1. Fate Data Gaps........................................................................................................... 19

7.8.2. Effects Data Gaps ...................................................................................................... 20

8. References................................................................................................................................ 23

Appendix A. Incidents.................................................................................................................. 25

Appendix B. The Risk Quotient Method and Levels of Concern................................................. 27

Appendix C. STIR Input/Output................................................................................................... 29
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1. Purpose

The purpose of this problem formulation is to provide the status of the environmental fate and 

ecological effects of dihydro-5-pentyl-2(3H)-furanone and dihydro-5-heptyl-2(3H)-furanone, 

which are commonly known as the furanones or tanol derivatives, considering their currently 

registered uses. The furanones are classified as lactones, which are cyclic esters of alphahydroxy acids. The furanones are registered nationally as insect, cat, and dog repellents. The 

insect repellent is formulated into a product called Bugchaser (dihydro-5-pentyl-2(3H)-furanone: 

0.024%; dihydro-5-heptyl-2(3H)-furanone: 0.049%; d-limonene: 4.015%) that is worn on 

humans as a wristband. The dog and cat repellent is formulated into a granule called Doo-Not for 

use in outdoor residential areas to discourage defecation (dihydro-5-pentyl-2(3H)-furanone: 

0.024%; dihydro-5-heptyl-2(3H)-furanone: 0.049%; d-limonene: 4.015%). Both products also 

contain the active ingredient d-limonene. This document will provide a plan for analyzing 

environmental fate and effects data relevant to the furanones and for conducting ecological risk 

and endangered species assessments for their registered uses. Additionally, this problem 

formulation is intended to identify data gaps, uncertainties, and potential assumptions used to 

address those uncertainties relative to characterizing the ecological risk associated with the 

registered uses of the furanones. 

The Health Effects Division (HED) informed the Environmental Fate and Effects Division 

(EFED) that a drinking water assessment would not be necessary for the furanones because 

human exposure due to the registered uses as pesticides is expected to be low and there are no 

food tolerances associated with either of the furanones. 

2. Problem Formulation

2.1. Nature of Regulatory Action

Under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), all pesticides distributed 

or sold in the United States generally must be registered by the Environmental Protection 

Agency (EPA). In determining whether a pesticide can be registered in the United States, EPA 

evaluates its safety to non-target species based on a wide range of environmental and health 

effects studies. In 1996, FIFRA was amended by the Food Quality Protection Act, and the 

Agency was mandated to implement a new program for the periodic review of pesticides, i.e., 

registration review.1

As part of the implementation of the new Registration Review program pursuant to Section 3(g) 

of the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA), the Agency is beginning its 

evaluation of the furanones to determine whether they continue to meet the FIFRA standard for 

registration. This problem formulation for the ecological risk and endangered species 

 The Registration Review program is intended to ensure 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 and the 

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

Through the new Registration Review program, the Agency periodically reevaluates pesticides to 

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

 1 http://www.epa.gov/oppsrrd1/registration_review/
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assessment chapter in support of the registration review will be posted in the initial docket, 

which will open the public phase of the review process.

2.2. Previous Assessments

2.2.1. Ecological Risk Assessments

The furanones were first registered as a pesticide in the United States in 1983 for use as a cat 

repellent. The Agency conducted an ecological risk assessment as part of the Reregistration 

Eligibility Decision (RED), which was finalized in 1996. Because all of the submitted 

ecotoxicity tests were conducted using a formulated product, data requirements were not 

satisfied. However, it was determined that the data for the formulated product was useful and 

would be relevant for other products with similar concentrations of the active ingredient. Data 

gaps were identified for the aquatic mosquito larvicide use; however, this use is no longer 

registered. Because no fate data had been submitted, aquatic exposure and, consequently, risk 

could not be quantified. Due to the low toxicity of the formulated products to birds and 

mammals, risk was not anticipated for terrestrial organisms, but risk could not be precluded for 

aquatic organisms. 

2.2.2. Drinking Water Exposure Assessments

No prior drinking water exposure assessments have been conducted for the furanones because 

human exposure due to the registered uses as pesticides is expected to be low and there are no 

food tolerances associated with either of the furanones. 

3. Stressor Source and Distribution

The furanones, along with the active ingredient d-limonene, are formulated into the product 

Bugchaser, which is an impregnated wristband worn by people to repel insects. However, the 

Bugchaser wristband product will not be evaluated in the ecological risk or endangered species 

assessments because environmental exposure is expected to be negligible. Doo-Not dog and cat 

repellent is a formulated product, which also contains both the furanones and d-limonene. It is a 

granule, which is sprinkled onto residential areas such as lawns, flowerbeds, driveways and 

sidewalks to discourage defecation. 

3.1. Mode of Action

The furanones, as well as d-limonene, are botanicals; however, the mode of action is not known. 

Because they are also used as a fragrance in cosmetics, the odors of the compounds are 

presumably undesirable to the target pests. As such, the furanones are presumed to be volatile. 

Although d-limonene is classified by the United States Food and Drug Administration to be 

“Generally Recognized as Safe” as a food additive, the furanones have not received this 

classification. 
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3.2. Overview of Pesticide Use and Usage

Table 3.1 summarizes the formulated products that are currently registered in the United States. 

There are no new pending uses for the furanones at this time. Table 3.2 presents the uses and 

corresponding application rates (single and maximum), application interval, and methods of 

application that will be considered in the registration review assessment. 

Because there were no limitations made on the amount that could be applied in a given area in a 

year, EFED conservatively extrapolated the label rates (per 100 square feet) to determine the 

amount active ingredient applied per acre (435.6 lb product/acre; 0.1045 lb diyhdro-5-pentyl2(3H)-furanone & 0.2134 lb dihydro-5-heptyl-2(3H)-furanone). In addition, EFED 

conservatively assumed that this amount would be applied once per week for 52 weeks. 

Although it is unlikely that 435.6 lb product would be applied on one acre since the product is 

sold in 2.5 lb bags, there were no label restrictions to prevent this conservative estimation of 

application rate. If the registrant revises the label prior to initiation of the risk assessment, EFED 

will certainly take the restrictions into consideration and revise the application rate if needed. 

Table 3.1. Summary of Furanones Products Registered in the United States

Product Name EPA Reg. 

No. Percent Active Ingredient Formulation

Bugchaser Insect 

Repellent Wristband 

Strip

66617-1

dihydro-5-pentyl-2(3H)-furanone: 0.024%

dihydro-5-heptyl-2(3H)-furanone: 0.049%

d-limonene: 4.015%

Impregnated 

Wristband

Doo-Not Dog and Cat 

Repellent 45987-1

dihydro-5-pentyl-2(3H)-furanone: 0.024%

dihydro-5-heptyl-2(3H)-furanone: 0.049%

d-limonene: 4.015%

Granule

Table 3.2. Maximum Labeled Application Rates for Doo-Not Dog and Cat Repellent

Use Formulation

Type

Application 

Method

Maximum Single 

Application Rate

(lb a.i./A)*

Maximum 

Number of 

Applications 

per Year

(#)

Maximum 

Seasonal 

Application 

Rate

(lb a.i./A)

Application 

Interval

(days)**

Residential Areas –

lawns, flowerbeds, 

driveways, 

sidewalks Granule Sprinkle

dihydro-5-pentyl2(3H)-furanone: 

0.1045

dihydro-5-heptyl2(3H)-furanone: 

0.2134

NS

(52) NS NS

(7)

NS – Not specified. The number in parentheses is EPA’s conservative assumption.

*Label states that 1 lb product per 100 square feet should be used for cats and 1 lb product per 100 square feet should be used for 

dogs for heavy infestations (1 lb product per 800 square feet for light infestations for dogs). These rates have been extrapolated to 

determine the application rate in terms of lb a.i./acre when considering the percent active ingredient. However, these extrapolated 

rates are likely an overestimation because they are based on 435.6 lb product applied per acre, which is unlikely because the 

product is sold in 2.5 lb bags. 

**Because the number of applications and application interval are not precisely specified (interval specified on label as after rains 

and at least once per week until problem behavior stops and to resume treatment if behavior recurs), 52 applications per year are 

assumed. Again, this is likely an overestimation considering the size of the bag.
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There is no national pesticide usage data available for the furanones, and there is no Screening 

Level Usage Analysis (SLUA) due to the lack of agricultural usage. Additionally, no usage data 

was available in the California Department of Pesticide Regulation Pesticide Use Reports for 

Doo-Not in 2009. 

3.3. Environmental Fate and Transport

No fate data have been submitted for the furanones. However, open literature data has been 

previously explored to determine physicochemical properties of lactones (the furanones belong 

to this chemical class) and their possible effect on environmental behavior.

This previous search showed that the furanones are classified as lactones. Lactones are cyclic 

esters, which can be synthesized by acidification of alpha-hydroxy acids (Morrison and Boyd, 

1973). Detoxification mechanisms of lactones can be accomplished through base-catalyzed 

hydrolysis or microbial-mediated degradation of reactive groups (Anderson et al., 1991). Deesterification may be catalyzed by metal ions, enzymes, and nucleophilic attack (e.g., OH-) 

(March, 1968). A new open literature search conducted on June 27, 2011 did not locate 

additional environmental fate data on the furanones. In summary, the Agency currently has no 

useable quantitative data on the fate and transport properties of the furanones. 

For the purposes of the proposed Registration Review risk assessment, the absence of 

environmental fate data will be addressed through the consultation of available structure-based 

predictors of environmental fate, a search for fate parameters associated with any chemical 

analogs, or assumption of stability for the various biotic and abiotic processes commonly 

considered for aquatic and terrestrial exposure modeling. At this point in time, the extent to 

which any or all of these approaches meets minimal confidence needs cannot be determined.

4. Receptors

Consistent with the process described in the Overview Document (U.S. EPA, 2004), the risk 

assessment for the furanones will rely on a surrogate species approach. Toxicological data 

generated from surrogate test species, which are intended to be representative of broad 

taxonomic groups, are used to extrapolate the potential effects on a variety of species (receptors) 

included under these taxonomic groupings. 

Acute and chronic toxicity data from studies submitted by pesticide registrants along with the 

available open literature are used to evaluate the potential direct and indirect effects of the 

furanones to aquatic and terrestrial receptors. This includes toxicity on the technical grade active 

ingredient, degradates, and, when available, formulated products (e.g., “Six-Pack” studies). The 

open literature studies are identified through EPA’s ECOTOXicology (ECOTOX) database, 

which employs a literature search engine for locating chemical toxicity data for aquatic life, 

terrestrial plants, and wildlife. The evaluation of both sources of data may also provide insight 

into the direct and indirect effects of the furanones on biotic communities from loss of species 

that are sensitive to the chemical and from changes in structure and functional characteristics of 

the affected communities. A search of the open literature data on the public version of 
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ECOTOX2 on June 23, 2011 did not yield any data. A more complete review of the ECOTOX 

database may be conducted for evaluation for possible quantitative and/or qualitative inclusion in 

this risk assessment.

A summary of the submitted data representing non-target organisms exposed to the furanones in 

aquatic and terrestrial habitats is provided in Sections 4.1 and 4.2, respectively. The incident 

database review for the furanones and a description of ecosystems potentially at risk are provided 

in Sections 4.3 and 4.4, respectively. 

4.1. Effects to Aquatic Organisms

A summary of aquatic toxicity data for the furanones from registrant-submitted studies is 

provided in Table 4.1. All of the studies were conducted using the formulated product NO-GO 

Dog Repellent (4.015% d-limonene; 0.024% dihydro-5-pentyl-2(3H)-furanone; 0.049% dihydro5-heptyl-2(3H)-furanone). All three of the aquatic studies were revisited during the problem 

formulation phase to recalculate toxicity values (DP 391731; September 15, 2011). They retain 

their supplemental classification because they were conducted with a formulated product that 

contains another active ingredient, d-limonene. It is important to note that the formulated product 

did not stay in solution throughout the studies, as evidenced by the observed precipitate, and this 

lends to the inherent uncertainty of the ability of the formulated product to predict the toxicity of 

the technical grade active ingredient. However, that fact that the formulation tested was a clay 

granule (likely source of the observed precipitate) and that structure based models for estimating 

organic chemical water solubility suggest furanone solubilities in excess of 1 g/L, the data still 

provide a reasonable though somewhat uncertain estimation of toxicity.

EFED consulted the database for d-limonene technical grade active ingredient to determine if 

this mixture constituent adequately accounts for observed toxicity of the above formulated 

product. EFED concludes that d-limonene alone does not account for observed toxicity in the 

available fish and aquatic invertebrate studies. Therefore, it is not possible to confidently 

determine if the effects observed were based solely on the furanones, and it is not possible to rule 

out effects that may have been attenuated by antagonism or enhanced by synergism. However, in 

the absence of furanones toxicity data for technical grade active ingredient, the Registration 

Review risk assessment will conservatively (as long as antagonism is a rare event) assume the 

furanones are the sole contributor for observed acute toxicity for freshwater fish and invertebrate 

endpoints generated with formulated product. This is believed to be conservative as it is 

empirically known that the d-limonene constituent does exert some toxic contribution to the 

mixture.

Table 4.1. Summary of the Endpoints from Submitted Aquatic Toxicity Studies for the Furanones

Study Type Species Toxicity Value Toxicity Classification MRID & Status

Acute –

Freshwater Fish

Rainbow trout

(Oncorhynchus mykiss)

96-hr LC50: 737.11 mg 

product/L 

NOAEC: 600 mg product/L 

Not applicable due to 

use of formulation

00109343

Supplemental

 2 http://cfpub.epa.gov/ecotox/
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Table 4.1. Summary of the Endpoints from Submitted Aquatic Toxicity Studies for the Furanones

Study Type Species Toxicity Value Toxicity Classification MRID & Status

Acute –

Freshwater Fish

Fathead minnow

(Pimephales promelas)

96-hr LC50: 966.49 mg 

product/L

NOAEC: 600 mg product/L

Not applicable due to 

use of formulation

00109344

Supplemental

Acute –

Freshwater 

Invertebrate

Water flea

(Daphnia magna)

48-hr LC50: 17.12 mg 

product/L

NOAEC: 10 mg product/L

Not applicable due to 

use of formulation

00109345

Supplemental

There are no estuarine/marine effects data for fish or invertebrates. Exposure to these organisms 

cannot be precluded due to the use patterns. For the purposes of the proposed Registration 

Review risk assessment, the absence of acute effects data for estuarine/marine fish and 

invertebrates will be addressed through the consultation of available structure-based predictors of 

aquatic organism toxicity, a search for effect endpoints associated with any chemical analogs, or 

an assumption of a conservative generalized adjustment factor that relates the available 

freshwater endpoints to estuarine/marine endpoints. At this point in time, the extent to which any 

or all of these approaches meets minimal confidence needs cannot be determined.

There are no chronic data available for any fish or invertebrate regardless of habitat type. Given 

expected assumptions of stability of the compound, in the absence of data to the contrary, it is 

reasonable at this time to assume that the compound will be present in the environment for 

extended periods of time. This suggests the need for chronic effects endpoints for aquatic 

organisms. For the purposes of the proposed Registration Review risk assessment, the absence of 

data on chronic effects to aquatic organism will be addressed through the consultation of 

available structure-based predictors of aquatic organism toxicity, a search for effect endpoints 

associated with any chemical analogs, or an assumption of a conservative generalized adjustment 

factor that relates the available acute endpoints to chronic endpoints. At this point in time, the 

extent to which any or all of these approaches meets minimal confidence needs cannot be 

determined. In addition, should fate property extrapolation efforts discussed above indicate that 

the furanones are more reasonably assumed to be highly instable, the risk assessment may 

reevaluate this chronic effects extrapolation approach.

There are no aquatic plant toxicity data for the furanones. For the purposes of the proposed 

Registration Review risk assessment, the absence of data on aquatic plant effects will be 

addressed through the consultation of available structure-based predictors of aquatic plant 

toxicity, a search for effect endpoints associated with any chemical analogs, or an assumption of 

a conservative generalized toxicity value from all available toxicity data. At this point in time, 

the extent to which any or all of these approaches meets minimal confidence needs cannot be 

determined. 

4.2. Effects to Terrestrial Organisms

Table 4.2 summarizes the terrestrial toxicity endpoints for the furanones based on an evaluation 

of submitted studies. All of the studies were conducted using the formulated product NO-GO 

Dog Repellent (4.015% d-limonene; 0.024% dihydro-5-pentyl-2(3H)-furanone; 0.049% dihydro5-heptyl-2(3H)-furanone). All three of the avian studies were revisited during the problem 

formulation phase and reclassified as supplemental because they were conducted with a 
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formulated product that contains another active ingredient, d-limonene (DP 391731; September 

15, 2011). 

The indeterminate nature of the endpoints for available formulated product for birds precludes an 

evaluation against d-limonene technical grade active ingredient as was done for aquatic 

organisms. Therefore, it is not possible to confidently determine if the effects observed were 

based solely on the furanones, and it is not possible to rule out effects precluded by antagonism. 

Given that d-limonene is not demonstrated to be toxic at the limit dose tested (5,600 mg/kg-diet), 

the Registration Review risk assessment will conservatively assume the furanones are the sole 

contributor for observed acute toxicity for avian endpoints generated with formulated product. 

The submitted mammalian studies were conducted using the formulated product rather than the 

TGAI. However, EFED is aware that there may be useful open literature regarding the toxicity of 

the furanones to mammals for both acute oral and reproductive toxic effects. EFED defers to 

HED for review of this data and selection of endpoints.

Table 4.2. Summary of the Endpoints from Submitted Terrestrial Toxicity Studies for the 

Furanones

Study Type Species Toxicity Value Toxicity Classification MRID & Status

Acute – Avian 

Oral

Bobwhite quail 

(Colinus virginianus)

LD50: >2000 mg product/kgbw/dayNot applicable due to 

use of formulation

00109340

Supplemental

Acute – Avian 

Dietary

Mallard duck 

(Anas platyrynchos) 

LC50: >5,000 mg 

product/kg-diet

Not applicable due to 

use of formulation

00103341

Supplemental

Acute – Avian 

Dietary

Bobwhite quail

(Colinus virginianus)

LC50: >5,000 mg 

product/kg-diet

Not applicable due to 

use of formulation

00109342

Supplemental

Acute –

Mammalian Oral Rat LD50: >5,000 mg product/kg Category IV 1996 RED

Acute –

Mammalian 

Inhalation

Rat

LC50: >5 mg product/L, 

using particle size of 297 

microns or less

Category IV 1996 RED

There are no chronic endpoints for birds or mammals identified at the time of drafting this 

problem formulation. Environmental instability is assumed for this chemical at this time. For the 

purposes of the proposed Registration Review risk assessment, the absence of effects data for 

chronic avian and mammalian organisms will be addressed through the consultation of available 

structure-based predictors of avian and mammalian toxicity (if any), a search for effect endpoints 

associated with any chemical analogs, or an assumption of a conservative generalized adjustment 

factor that relates the available acute endpoints to chronic endpoints. At this point in time, the 

extent to which any or all of these approaches meets minimal confidence needs cannot be 

determined. In addition, should fate property extrapolation efforts discussed above indicate that 

the furanones are more reasonably assumed to be highly instable, the risk assessment may 

reevaluate this chronic effects extrapolation approach.

There are neither terrestrial plant nor terrestrial invertebrate toxicity data for the furanones. For 

the purposes of the proposed Registration Review risk assessment, the absence of effects data 

for terrestrial plant and invertebrate will be addressed through the consultation of available 

structure-based predictors of toxicity (if any), a search for effect endpoints associated with any 

chemical analogs, or an assumption of a conservative generalized toxicity value from all 
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available pesticide data. At this point in time, the extent to which any or all of these approaches 

meets minimal confidence needs cannot be determined. 

4.3. Incident Databases Review

Preliminary reviews of the Ecological Incident Information System (EIIS, version 2.1) and the 

Avian Incident Monitoring System (AIMS)3 were conducted on June 23, 2011 for the furanones, 

as well as d-limonene. There were no avian incidents reported in the AIMS database. There 

were no incidents reported in the EIIS database. 

In addition to the incidents recorded in EIIS and AIMS, additional incidents can be reported to 

the Agency in an aggregated format. Pesticide registrants report certain types of incidents to the 

Agency as aggregate counts of incidents occurring per product per quarter. Ecological incidents 

reported in aggregate reports include those categorized as ‘minor fish and wildlife’ (W-B), 

‘minor plant’ (P-B), and ‘other non-target’ (ONT) incidents. ‘Other non-target’ incidents include 

reports of adverse effects to insects and other terrestrial invertebrates. One minor aggregate 

incident report involving plants has been submitted to the Agency for the furanones; however, 

the product used was Home Defense Indoor Insect Killer, which is not currently registered for 

the furanones.

Due to limitations with data in the EIIS, a lack of reported incidents in the database cannot be 

used as evidence that additional incidents have not occurred. Incident reports for non-target 

plants and animals typically provide information on mortality events only. Reports for other 

adverse effects, such as reduced growth or impaired reproduction, are rarely received. EPA’s 

changes in the registrant reporting requirements of incidents may also account for the reduced 

number of reported incidents. Registrants are now only required to submit detailed information 

on ‘major’ incidents. Minor incidents are generally reported aggregately and are not included in 

EIIS. In addition, there have been changes in state monitoring efforts due to lack of resources. 

4.4. Ecosystems Potentially at Risk

The ecosystems at risk are often extensive in scope; therefore, it may not be possible to identify 

specific ecosystems during the development of a nation-wide ecological risk assessment. 

However, in general terms, terrestrial ecosystems potentially at risk could include the treated 

area and immediately adjacent areas that may receive runoff. Areas adjacent to the treated area 

could include cultivated fields, fencerows and hedgerows, meadows, fallow fields or grasslands,

woodlands, riparian habitats and other uncultivated areas. 

Aquatic ecosystems potentially at risk include water bodies adjacent to or downstream from the 

treated area and could include impounded bodies such as ponds, lakes and reservoirs, or flowing 

waterways such as streams or rivers. For uses in coastal areas, aquatic habitat also includes 

marine ecosystems, including estuaries. 

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

Assessment endpoints represent the actual environmental value that is to be protected, defined by 

an ecological entity (species, community, or other entity) and its attribute or characteristics (U.S. 

EPA, 1998). For the furanones, the ecological entities may include the following: birds, 

mammals, terrestrial-phase amphibians, reptiles, freshwater fish and invertebrates, aquatic-phase 

amphibians, estuarine/marine fish and invertebrates, terrestrial plants, terrestrial invertebrates, 

and aquatic plants. The attributes for each of these entities include survival, growth, and 

reproduction.

6. Conceptual Model

For a pesticide to pose an ecological risk, it must reach ecological receptors in biologically 

significant concentrations. An exposure pathway is the means by which a pesticide moves in the 

environment from a source to an ecological receptor. For an ecological pathway to be complete, 

it must have a source, a release mechanism, an environmental transport medium, a point of 

exposure for ecological receptors, and a feasible route of exposure.

The conceptual model for the furanones provides a written description and visual representation 

of the predicted relationships between the furanones, potential routes of exposure, and the 

predicted effects for the assessment endpoint. A conceptual model consists of two major 

components: risk hypothesis and a conceptual diagram (U.S. EPA, 1998).

6.1. Risk Hypothesis

A risk hypothesis describes the predicted relationship among the stressor, exposure, and 

assessment endpoint response along with the rationale for their selection. For the furanones, the 

following ecological risk hypothesis is being employed for this ecological risk assessment:

Based on the application methods, the assumed fate and transport, and the assumed 

sensitivity of non-target aquatic and terrestrial species, the furanones have the potential 

to reduce survival, reproduction, and/or growth in non-target terrestrial and aquatic 

organisms when used in accordance with the current labels. These non-target organisms 

include Federally-listed threatened and endangered species as well as non-listed species. 

6.2. Conceptual Diagram

Runoff and direct consumption of the granules are the potential transport mechanisms of the 

furanones to aquatic and terrestrial habitats where non-target organisms may be exposed. These 

transport mechanisms (i.e., sources) are depicted in the conceptual models below (Figures 6.1,

6.2, and 6.3) along with the receptors of concern and the potential attribute changes in the 

receptors due to exposure to the furanones. 
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Generally, the Screening Imbibition Program model (SIP v.1.0)4 is used to determine whether 

dew and puddles, utilized as drinking water, on the field is a significant exposure route for birds 

and mammals (Figure 6.3). However, the model was not used for the furanones because chronic 

avian and mammalian toxicity data was not submitted. Therefore, drinking water is 

conservatively assumed to be a significant route of exposure to terrestrial animals given the use 

pattern. 

Figure 6.1. Conceptual Model for Furanones Exposure and Effects to Aquatic Organisms. 

Dotted Lines Indicate Exposure Pathways that Have a Low Likelihood of Contributing to 

Ecological Risk.

 4 http://www.epa.gov/oppefed1/models/terrestrial/sip/sip_user_guide.html

** Route of exposure includes only ingestion of fish and aquatic

Stressor

Source

Receptors

Attribute

Change

Furanones applied to use site

Pesticide drift

Aquatic animals

Invertebrates 

Vertebrates

**Piscivorous mammals 

 and birds 

Individual 

organisms

Reduced survival

Reduced growth

Reduced reproduction

Food chain

Reduction in algae and 

 vascular plants

Reduction in prey

Modification of PCEs 

 related to prey availability

Habitat integrity

Reduction in primary 

productivity

Reduced cover

Community change

Modification of PCEs related to 

 habitat

Surface water/

Sediment

Runoff

Aquatic Animals

Invertebrates

Vertebrates

Exposure

Media

Uptake/gills 

or integument

Ingestion Ingestion

Atmospheric 

transport

Wet/dry deposition

Soil Leaching to

Groundwater

Uptake/gills 

or integument

Aquatic Plants

Non-vascular

Vascular

Uptake/cell, 

roots, leaves Riparian plants

terrestrial 

exposure 

pathways see 

Figure 6.2
-14 of 31-

Figure 6.2. Conceptual Model for Furanones Exposure and Effects to Terrestrial 

Organisms. Dotted Lines Indicate Exposure Pathways that Have a Low Likelihood of 

Contributing to Ecological Risk.

Stressor

Source

Attribute

Change

Furanones applied to use site

Direct

application

Pesticide

drift

Terrestrial 

vertebrates*

Terrestrial 

Inverts*

Individual organisms

Reduced survival

Reduced growth

Reduced reproduction

Food chain

Reduction in prey and food

Modification of PCEs 

 related to prey availability

Habitat integrity

Reduction in primary productivity

Reduced cover

Community change

Modification of PCEs related

 to habitat

Terrestrial plants

grasses/forbs, fruit, seeds 

(trees, shrubs)

Runoff

Terrestrial 

vertebrates* 

Exposure 

Media 

& Receptors

Soil

Ingestion

Ingestion

Dermal uptake/Ingestion

Atmospheric 

transport

Root uptake/contact

Wet/dry deposition

Ingestion

Leaching to

Groundwater Irrigation 

water

* See Figure 6.3 for drinking water and inhalation exposure pathways for terrestrial vertebrates and ingestion of residues in dew 

by terrestrial invertebrates. 
-15 of 31-

Figure 6.3. Drinking Water and Inhalation Exposure Pathways for Terrestrial Vertebrates 

and Ingestion of Residues in Dew by Terrestrial Invertebrates. Dotted Lines Indicate 

Exposure Pathways that Have a Low Likelihood of Contributing to Ecological Risk.

7. Analysis Plan

In order to address the risk hypothesis, the potential for adverse effects on the environment will 

be estimated. The use, environmental fate, and ecological effects of the furanones will be

characterized and integrated to assess the risks. Risk quotients (RQs) will be derived for the 

furanones by dividing estimated environmental concentrations (EEC) by the most sensitive 

endpoint from the relevant, available toxicity data for the furanones.

This analysis plan will be revisited and may be revised depending upon a full review of the data 

available in the open literature and the information submitted by the public in response to the 

opening of the Registration Review docket.

Stressor

Source

Attribute

Change

Furanones applied to use site

Direct

application Pesticide drift

Terrestrial 

vertebrates

Terrestrial 

invertebrates

Individual 

organisms

Reduced survival

Reduced growth

Reduced reproduction

Food chain

Reduction in prey and 

food

Modification of PCEs 

 related to prey availability

Habitat integrity

Reduction in primary productivity

Reduced cover

Community change

Modification of PCEs related

 to habitat

Runoff

Exposure Media Dew (formed on 

terrestrial plants)

Atmospheric 

transport

Receptors

Puddles (formed 

on treated fields)

Inhalation Ingestion

Air
-16 of 31-

7.1. Stressors of Concern

The Agency does not routinely include, in its risk assessments, an evaluation of mixtures of 

active ingredients, either those mixtures of multiple active ingredients in product formulations or 

those in the applicator’s tank. In the case of the product formulations of multiple active 

ingredients (that is, a registered product containing more than one active ingredient), each active 

ingredient is subject to an individual risk assessment for regulatory decision regarding the active 

ingredient on a particular use site. The only two products registered for the furanones also 

contain the active ingredient d-limonene. Registration Review for d-limonene began in 2010. 

Because the only effects data that are available are for the formulated product containing more 

than one active ingredient, they will be used qualitatively or quantitatively in accordance with 

the Agency’s Overview Document and the Services’ Evaluation Memorandum (U.S. EPA, 2004; 

USFWS/NMFS, 2004). 

7.2. Measures of Exposure

In order to estimate risks of exposure to the furanones in aquatic and terrestrial environments, all 

exposure modeling and resulting risk conclusions will be based on registered labels including 

maximum application rates and methods cited in Table 3.2 for the one use that results in 

environmental exposure. Measures of exposure are based on aquatic and terrestrial models that 

predict estimated environmental concentrations (EECs) of the furanones. Several models are 

available to predict aquatic EECs, including FIRST, GENEEC, Pesticide Root Zone Model 

coupled with the Exposure Analysis Model System (PRZM/EXAMS), and SCI-GROW. The 

model used to predict terrestrial EECs on food items, or in the case of a granular application, the 

LD50/square foot, is T-REX (version 1.4.1, October 2008). The model used to derive EECs 

relevant to terrestrial and wetland plants is TerrPlant (version 1.2.2, December 2006). These 

models are parameterized using relevant reviewed environmental fate data from registrant 

submissions and the open literature when available; model input values will be consistent with 

the most recent version of the input parameter guidance (Version 2.1; EFED 2009). For more 

detailed descriptions, exposure models and their associated user guides can be located on the 

Office of Pesticide Programs Models and Databases website.5

The use of modeling to provide aquatic EECs depends on the submission of outstanding 

environmental fate and product chemistry data, which are currently considered data gaps. 

However, if data are not received, EFED will conservatively assume that the furanones are 

stable. 

In addition to modeling estimates, available monitoring data will be evaluated. Monitoring data 

will include those collected/reported by states and other federal departments/agencies.6

 5 http://www.epa.gov/pesticides/science/models_db.htm

6 USGS National Water Quality Assessment (NAQWA; http://water.usgs.gov/nawqa)
-17 of 31-

7.3. Measures of Effect

Ecological effects data are used as measures of direct and indirect effects to biological receptors. 

Data are obtained from registrant-submitted studies or from literature studies identified by 

ECOTOX. The ECOTOX database provides more ecological effects data in an attempt to bridge 

existing data gaps. ECOTOX is a source for locating single chemical toxicity data and potential 

chemical mixture toxicity data for aquatic life, terrestrial plants, and wildlife. ECOTOX was 

created and is maintained by EPA, Office of Research and Development, and the National Health 

and Environmental Effects Research Laboratory's Mid-Continent Ecology Division.

Information on the potential effects of the furanones on non-target animals is also collected from 

the Ecological Incident Information System (EIIS; U.S. EPA, 2007c). The EIIS is a database 

containing adverse effect (typically mortality) reports on non-target organisms where such 

effects have been associated with the use of pesticides. Incidents reported in the aggregate 

incident reports and the Avian Incident Monitoring System (AIMS) will also be searched.7

 

AIMS is a database administered by the American Bird Conservancy (partially funded by EPA). 

It contains publicly available data on reported avian incidents involving pesticides.

Where available, sub-lethal effects observed in both registrant-submitted and open literature 

studies will be evaluated qualitatively. Such effects may include behavioral changes (e.g., 

lethargy and changes in coloration). Quantitative assessments of risks, though, are limited to 

those endpoints that can be directly linked to the Agency’s assessment endpoints of impaired 

survival, growth and reproduction.

The assessment of risk for direct effects to non-target organisms makes the assumption that 

toxicity of the furanones to terrestrial-phase amphibians and reptiles is similar to birds. The 

same assumption is made for the toxicity to aquatic-phase amphibians being similar to fish. 

The acute measures of effect used for animals in this assessment are the LD50, LC50 and EC50. 

LD stands for "Lethal Dose", and LD50 is the amount of a material, given all at once, that is 

estimated to cause the death of 50% of the test organisms. LC stands for “Lethal Concentration” 

and LC50 is the concentration of a chemical that is estimated to kill 50% of the test organisms. 

EC stands for “Effective Concentration” and the EC50 is the concentration of a chemical that is 

estimated to produce a specific effect in 50% of the test organisms. Endpoints for chronic 

measures of exposure for listed and non-listed animals are the NOAEL/NOAEC and NOEC. 

NOAEL stands for “No Observed-Adverse-Effect-Level” and refers to the highest tested dose of 

a substance that has been reported to have no harmful (adverse) effects on test organisms. The 

NOAEC (i.e., “No-Observed-Adverse-Effect-Concentration”) is the highest test concentration at 

which none of the observed effects were statistically different from the control. The NOEC is 

the No-Observed-Effects-Concentration. For non-listed plants, only acute exposures are 

assessed (i.e., EC25 for terrestrial plants and EC50 for aquatic plants); for listed plants, either the 

NOAEC or EC05 is used. 

 7 http://www.abcbirds.org/abcprograms/policy/pesticides/aims/aims/index.cfm
-18 of 31-

The evaluation of the measures of effects, as described above, and the following description of 

the integration of exposure and effects depend on the submission of several outstanding 

environmental effects studies, which are currently considered data gaps. If acceptable data are 

not submitted, EFED will conservatively assume that all effects observed in the submitted data 

are due to the furanones and that d-limonene does not contribute to the toxicity of the

formulation (i.e., the acute freshwater LC50 of 568 mg product/L will be interpreted as 0.28 mg 

a.i./L for dihydro-heptyl-2(3H)-furanone and 0.14 mg a.i./L for dihydro-pentyl-2(3H)-furanone, 

thus classifying both the furanones as highly toxic to freshwater fish). Taxa for which data have 

not been submitted will result in the assumption of risk to listed species. 

7.4. Integration of Exposure and Effects

Risk characterization is the integration of exposure and ecological effects characterization to 

determine the potential ecological risk from the use of the furanones and the likelihood of direct 

and indirect effects to non-target organisms in aquatic and terrestrial habitats. For the 

assessment of the risks of the furanones, the risk quotient (RQ) method is used to compare 

exposure and measured toxicity values. EECs are divided by acute and chronic toxicity values. 

The resulting RQs are then compared to the Agency’s Levels of Concern (LOC) (U.S. EPA, 

2004). These criteria are used to indicate when use of the furanones, as directed on the label, has

the potential to cause adverse direct or indirect effects to non-target organisms. In addition, 

incident data from EIIS, aggregate incident reports, and AIMS will be considered as part of the 

risk characterization.

7.5. Deterministic and Probabilistic Assessment Methods

The quantitative assessment of risk will primarily depend on the deterministic point-estimate 

based approach described in the risk assessment. Depending on the risk manager’s need for 

additional information regarding risk, an effort will be made to further describe risk using 

probabilistic tools that the Agency has developed. These tools have been reviewed by FIFRA 

Scientific Advisory Panels and have been deemed as appropriate means of refining assessments 

where deterministic approaches have identified risks.8

7.6. Endangered Species Assessment

Consistent with the Agency’s responsibility under the Endangered Species Act (ESA), the 

Agency will evaluate risks to Federally-listed threatened and/or endangered (listed) species from 

registered uses of the furanones. This assessment will be conducted in accordance with the 

Overview Document (U.S. EPA, 2004), provisions of the ESA, and the Services’ Endangered 

Species Consultation Handbook (USFWS/NMFS, 1998).

The assessment of effects associated with the registration of the furanones is based on an action 

area. The action area is considered to be the area directly or indirectly affected by the federal 

action, as indicated by the exceedance of Agency Levels of Concern (LOCs) used to evaluate 

direct or indirect effects. The Agency’s approach to defining the action area under the provisions 

 8 http://www.epa.gov/scipoly/sap/index.htm
-19 of 31-

of the Overview Document (U.S. EPA, 2004) considers the results of the risk assessment process 

to establish boundaries for that action area with the understanding that exposures below the 

Agency’s defined LOCs constitute a no-effect threshold. For the purposes of this assessment, 

attention will be focused on the footprint of the action (i.e., the area where application occurs), 

plus all areas where offsite transport (i.e., runoff.) may result in potential exposure that exceeds 

the Agency’s LOCs. Specific measures of ecological effect that define the action area for listed 

species include any direct and indirect effects and/or potential modification of its critical habitat, 

including reduction in survival, growth, and reproduction as well as the full suite of sub-lethal

effects available in the effects literature. Therefore, the action area extends to a point where 

environmental exposures are below any measured lethal or sub-lethal effect threshold for any 

biological entity at the whole organism, organ, tissue, and cellular level of organization. In 

situations where it is not possible to determine the threshold for an observed effect, the action 

area will be assumed to encompass the entire United States.

7.7. Drinking Water Assessment

No prior drinking water assessments have been conducted. HED informed EFED that a drinking 

water assessment would not be required for registration review.

7.8. Preliminary Identification of Data Gaps

Use of the furanones is defined as having terrestrial residential uses. According to the Code of 

Federal Regulations 40 (CFR40 2007) Part 158 Subpart D (data requirements for pesticides) 

environmental fate and non-target organism effects data are required for the furanones based on 

its terrestrial use. Available studies submitted to fulfill environmental fate and ecological effects 

guideline requirements, as well as outstanding data gaps for the furanones, are defined in 

Sections 7.8.1 and 7.8.2. 

7.8.1. Fate Data Gaps

There is no submitted environmental fate data. Data gaps for outdoor residential uses are 

identified in Table 7.1. In addition, product chemistry data is required. 

If data are not submitted, EFED will proceed as described in Section 3.3.

Table 7.1. Environmental Fate Data Gaps for Outdoor Residential Uses

Guideline Description Data Gap? Comments

Not applicable Product Chemistry Data Yes These studies are required 

for terrestrial residential 

uses. Studies should be 

conducted with each 

furanone as the technical 

grade active ingredient.

835.2120

161-1

Hydrolysis Yes

835.4100

162-1

Aerobic Soil Metabolism Yes

835.1230

835.1240

163-1

Leaching

Adsorption/Desorption

Yes
-20 of 31-

Table 7.1. Environmental Fate Data Gaps for Outdoor Residential Uses

Guideline Description Data Gap? Comments

835.6100

164-1

Terrestrial Field Dissipation Yes

7.8.2. Effects Data Gaps

Although some submissions have been made to provide data on the effects of the furanones to 

aquatic and terrestrial organisms, data gaps still exist and are included in Tables 7.2 to 7.4, 

below. 

If acceptable data are not submitted, EFED will proceed as described in Section 4. 

STIR Analysis

Because the furanones are presumed to be volatile due to their presumed mode of action, the 

Screening Tool for Inhalation Risk (STIR v.1.0)9

 9 http://www.epa.gov/oppefed1/models/terrestrial/stir/stir_user_guide.html

was used to determine whether an avian 

inhalation risk should be required. Because product chemistry data was not submitted, 

EPISUITE was used to predict vapor pressures for both the furanones. For dihydro-pentyl2(3H)-furanone, the vapor pressure was predicted to be 0.0119 mm Hg. For dihydro-heptyl2(3H)-furanone, the vapor pressure was predicted to be 0.00409 mm Hg. In the absence of 

toxicity data conducted with the TGAI, formulation data was converted and input into STIR. The 

acute oral avian LD50 of >2000 mg product/kg-bw/day was converted to 0.98 mg a.i./kg-bw, the 

acute oral rat LD50 of >5000 mg product/kg was converted to 2.45 mg a.i./kg, and the 

mammalian inhalation LC50 of >5 mg product/L was converted to 0.00245 mg a.i./L. For 

dihydro-pentyl-2(3H)-furanone, 0.1045 lb a.i./acre was the selected application weight, and the 

molecular weight was 156.23 g/mole. For dihydro-heptyl-2(3H)-furanone, 0.2134 lb a.i./acre was 

the selected application weight, and the molecular weight was 184.28 g/mole. Although it is a 

conservative screen due to the use of predicted product chemistry data and extrapolated toxicity 

values, STIR indicated that inhalation risk may be possible and that refinements should be 

pursued. Therefore, an avian inhalation study is considered a data gap. See Appendix C for 

STIR inputs and outputs. 
-21 of 31-

Table 7.2. Available Ecological Effects Data for Terrestrial Animals Exposed to the Furanones

and Remaining Data Gaps for Outdoor Residential Uses

Guideline Description MRID/

Accession Classification Data Gap? Comments

850.2100 Avian oral 

toxicity 00109340 Supplemental Yes1

1

The submitted studies were conducted with 

a formulated product that contained an 

additional active ingredient (d-limonene). 

Studies are required for each furanone 

using the technical grade active ingredient 

for either an upland game or waterfowl 

species and a passerine species. 

2

The submitted studies were conducted with 

a formulated product that contained an 

additional active ingredient (d-limonene). 

Studies are required for each furanone 

using the technical grade active ingredient 

for both an upland game and waterfowl 

species.

3

Studies were not submitted. Studies are 

required for each furanone using the 

technical grade active ingredient for both 

for an upland game and waterfowl species.

4

Study was not submitted. Studies are 

required for each furanone using the 

technical grade active ingredient.

5

The submitted studies were conducted with 

a formulated product that contained an 

additional active ingredient (d-limonene). 

Studies are required for each furanone 

using the technical grade active ingredient. 

6

The Screening Tool for Inhalation Risk 

(STIR v.1.0) suggested that refinements be 

pursued for addressing avian inhalation risk. 

Therefore, an avian inhalation study is 

considered a data gap. However, the model 

is based on conservatively predicted vapor 

pressures and extrapolated toxicity data; 

therefore, EFED would prefer to use a 

tiered approach in this situation – acute oral 

and dietary avian studies conducted with the 

TGAI should be submitted first. When this 

data is input into STIR and if a need for 

refinement is still indicated, then an avian 

inhalation study should be submitted.

850.2200 Avian dietary 

toxicity

00103341 Supplemental

Yes2

00109342 Supplemental

850.2300 Avian 

reproduction

Not 

submitted Not applicable

Yes3

Not 

submitted Not applicable

850.3020 Honeybee acute 

contact toxicity

Not 

submitted Not applicable Yes4

870.1100

Mammalian 

acute oral 

toxicity

1996 RED Not available Yes5

870.3800

Mammalian 2-

generation 

reproduction

Not 

submitted Not applicable Yes4

870.1300

Mammalian 

inhalation 

toxicity

1996 RED Not available Yes5

Other Avian inhalation 

toxicity

Not 

submitted Not applicable Yes6
-22 of 31-

Table 7.3. Available Ecological Effects Data for Aquatic Animals Exposed to the Furanones 

and Remaining Data Gaps

Guideline Description MRID/ 

Accession Classification Data Gap? Comments

850.1075 Freshwater fish –

Acute toxicity 

00109343 Supplemental Yes1

1

The submitted studies were 

conducted using a formulated 

product that contained another 

active ingredient (d-limonene). 

Studies are required for each

furanone using the technical grade 

active ingredient.

2

Studies were not submitted. 

Studies are required for each

furanone using the technical grade 

active ingredient. 

3

In the absence of fate data, it is not 

possible to determine if sediment 

toxicity studies are required. These 

studies remain reserved.

All other studies not currently 

classified as data gaps remain 

reserved.

00109344 Supplemental

850.1075 Estuarine/marine fish –

Acute toxicity 

Not 

submitted Not applicable Yes2

850.1010

Freshwater 

invertebrates –

Acute toxicity

00109345 Supplemental Yes1

850.1025

850.1035

Estuarine/marine

invertebrates –

Acute toxicity 

Not 

submitted Not applicable

Yes2

Not 

submitted Not applicable

850.1400 Freshwater fish –

early life stage test

Not 

submitted Not applicable Yes2

850.1400 Estuarine/marine fish –

early life stage test

Not 

submitted Not applicable No

850.1300

Freshwater 

invertebrate –

life cycle test

Not 

submitted Not applicable Yes2

850.1350

Estuarine/marine

invertebrates –

life cycle test

Not 

submitted Not applicable No

850.1735

Freshwater 

invertebrate – Acute 

whole sediment

Not 

submitted Not applicable No3

850.1740

Estuarine/marine 

invertebrate – Acute 

whole sediment

Not 

submitted Not applicable No3

Other

Freshwater and 

estuarine/marine 

invertebrate – Chronic 

whole sediment

Not 

submitted Not applicable No3

No plant studies were submitted. Data gaps are identified in Table 7.4.
-23 of 31-

Table 7.4. Terrestrial and Aquatic Plant Data Gaps for the Furanones

Guideline Description Data Gap? Comments

850.4100

Terrestrial Plant 

toxicity: Tier I

seedling emergence

Yes1

1

Because the formulated 

product is a granule, only 

seedling emergence 

toxicity testing is 

required using the 

technical grade active 

ingredient (not TEP) for 

each furanone. 

2

Acceptable data are 

required for non-vascular 

and vascular plants using 

the technical grade active 

ingredient for each

furanone.

850.4150

Terrestrial Plant 

toxicity: Tier I

vegetative vigor

No1

850.5400 Aquatic Plant Growth: 

algae Yes2

850.4400 Aquatic Plant Growth: 

vascular plants Yes2

8. References

Food and Agriculture Organization of the United Nations (FAO). 2000. Appendix 2. Parameters of pesticides that 

influence processes in the soil. In FAO Information Division Editorial Group (Ed.), Pesticide Disposal 

Series 8. Assessing Soil Contamination: A Reference Manual. Rome: Food & Agriculture Organization of 

the United Nations. http://www.fao.org/DOCREP/003/X2570E/X2570E06.htm

Fletcher, J.S., J.E. Nellessen, and T.G. Pfleeger. 1994. Literature review and evaluation of the EPA food-chain 

(Kenaga) nomogram, an instrument for estimating pesticide residues on plants. Environ. Tox. Chem. 

13:1383-1391.

Hoerger, F. and E. E. Kenaga. 1972. Pesticide Residues on Plants: Correlation of Representative Data as a Basis 

for Estimation of their Magnitude in the Environment. In F. Coulston and F. Korte, eds., Environmental 

Quality and Safety: Chemistry, Toxicology, and Technology, Georg Thieme Publ., Stuttgart, West 

Germany, pp. 9-28.

March, J. 1968. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure. McGraw-Hill Company, New 

York.

Morrison, R. and R. Boyd. 1973. Organic Chemistry. 3rd edition. Allyn and Bacon, Inc. Boston. 

U.S. Department of Agriculture (USDA). 2007. National Agricultural Statistics Service. United States Department 

of Agriculture. http://www.nass.usda.gov/

USEPA. 1998. Guidelines for Ecological Risk Assessment. Risk Assessment Forum, Office of Research and 

Development, Washington, D.C. EPA/630/R-95/002F. April 1998. 

http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=30759

USEPA. 2002. Guidance for Selecting Input Parameters in Modeling the Environmental Fate and Transport of 

Pesticides, Version II. US Environmental Protection Agency, Washington DC. Online at: 

http://www.epa.gov/oppefed1/models water/input_guidance2_28_02.htm.

USEPA. 2004. Overview of the Ecological Risk Assessment Process in the Office of Pesticide Programs. U.S. 

Environmental Protection Agency, Office of Prevention, Pesticides and Toxic Substances, Office of 

Pesticide Programs, Washington DC. January 23, 2004.
-24 of 31-

USEPA. 2006a. Standardized Soil Mobility Classification Guidance. U.S. Environmental Protection Agency, 

Office of Prevention, Pesticides and Toxic Substances, Office of Pesticide Programs, Environmental Fate 

and Effects Division, Memorandum. April 21, 2006. 

USEPA. 2007c. Ecological Incident Information System. http://www.epa.gov/espp/consultation/ecoriskoverview.pdf

USEPA. 2010d. 40 CFR Part 158. Data Requirements for Pesticides. July 1, 2010.

USEPA. 2007e. ECOTOXicology Database. Office of Research and Development National Health and 

Environmental Effects Research Laboratory’s (NHEERL’s) Mid-Continent Ecology Division (MED). 

http://cfpub.epa.gov/ecotox/.

U.S. Fish and Wildlife Service (USFWS) and National Marine Fisheries Service (NMFS). 1998. Endangered 

Species Consultation Handbook: Procedures for Conducting Consultation and Conference Activities Under 

Section 7 of the Endangered Species Act. Final Draft. March 1998.

Williams, G. M. and J.H. Weisburger. 1991. Chemical Carcinogenesis in Casarett and Doul's Toxicology: The Basic 

Science of Poisons edited by Mary Amdur, Ph.D., John Doull, Ph.D., M.D., and Curtis D. Klaassen, Ph.D. 

4th edition. Pergamon Press, New York. 

Worthing, C. R and R. J. Hance, editors. 1991. The Pesticide Manual: A World Compendium (9th edition). British 

Crop Protection Council, Surrey, UK. June, 1991.
-25 of 31-

Appendix A. Incidents

A search for ecological incidents related to use of the furanones, conducted on June 23, 2011, 

yielded no incidents. 

Uncertainties Related to the Use of Incident Information from the Ecological Incident 

Information System 

Incident data are used in risk assessments to provide evidence that the risk predictions from the 

screening level assessment are supported by actual effects in the field. Incident reports 

submitted to EPA since approximately 1994 have been tracked by assignment of incident 

numbers in an Incident Data System (IDS), microfiched, and then entered to a second database, 

the Ecological Incident Information System (EIIS). Additionally, there is an on-going effort to 

enter information to EIIS on incident reports received prior to establishment of current databases. 

Incident reports are not received in a consistent format (e.g., states and various labs usually have 

their own formats), may involve multiple incidents involving multiple chemicals in one report, 

and may report on only part of a given incident investigation (e.g., residues). 

Incidents entered into EIIS are categorized into one of several certainty levels regarding the 

likelihood that a particular pesticide is associated with the incident: highly probable, probable, 

possible, unlikely, or unrelated. In brief, “highly probable” incidents usually require carcass 

residues and/or clear circumstances regarding the exposure. “Probable” incidents include those 

where residues were not available and/or circumstances were less clear than for “highly 

probable.” “Possible” incidents include those where multiple chemicals may have been involved 

and it is not clear what the contribution was of a given chemical. The “unlikely” category is 

used, for example, where a given chemical is practically nontoxic to the category of organism 

killed and/or the chemical was tested for but not detected in samples. “Unrelated” incidents are 

those that have been confirmed to be not pesticide-related.

Incidents entered into the EIIS are also categorized as to use/misuse. Unless specifically 

confirmed by a state or federal agency to be misuse, or there was very clear misuse such as 

intentional baiting to kill wildlife, incidents are not typically considered misuse. 

The number of documented kills in EIIS is believed to be a small fraction of total mortality 

caused by pesticides. Mortality incidents must be seen, reported, investigated, and have 

investigation reports submitted to EPA to have the potential for entry into the database. 

Incidents often are not seen, due to scavenger removal of carcasses, decay in the field, or simply 

because carcasses may be hard to see on many sites and/or few people are systematically 

looking. Poisoned animals may also move off-site to less conspicuous areas before dying. 

Incidents may not get reported to appropriate authorities capable of investigating the incident for 

a variety of reasons including the finder may not know of the importance of reporting incidents, 

may not know who to call, may not feel they have the time or desire to call, or may hesitate to 

call because of their own involvement in the kill. Incidents reported may not get investigated if 

resources are limited or may not get investigated thoroughly, with residue analyses, for example. 

Also, if kills are not reported and investigated promptly, there will be little chance of 
-26 of 31-

documenting the cause, since tissues and residues may deteriorate quickly. Reports of 

investigated incidents often do not get submitted to EPA, since reporting by states is voluntary. 

Furthermore, the database relies heavily on registrant-submitted incident reports, and registrants 

are currently only required to submit detailed information on ‘major’ ecological incidents, while 

‘minor’ incidents are reported aggregately. 

Based on the 40 CFR (§159.184 Toxic or adverse effect incident reports), an ecological incident 

is considered ‘major’ if any of the following criteria are met:

Fish or wildlife:

(A) Involves any incident caused by a pesticide currently in Formal Review for 

ecological concerns. 

(B) Fish: Affected 1,000 or more individuals of a schooling species or 50 or more 

individuals of a non-schooling species. 

(C) Birds: Affected 200 or more individuals of a flocking species, or 50 or more 

individuals of a songbird species, or 5 or more individuals of a predatory species. 

(D) Mammals, reptiles, amphibians: Affected 50 or more individuals of a relatively 

common or herding species or 5 or more individuals of a rare or solitary species. 

(E) Involves effects to, or illegal pesticide treatment (misuse) of a substantial tract of 

habitat (greater than or equal to 10 acres, terrestrial or aquatic). 

Plants: 

(A) The effect is alleged to have occurred on more than 45 percent of the acreage 

exposed to the pesticide.

All other ecological incidents are considered ‘minor’ and only need to be aggregately reported. 

‘Minor’ incidents reported by the registrants are not included in the EIIS database. Therefore, 

for example, an incident could affect 900 fish, 150 birds, 45 mammals, and 40% of an exposed 

crop and not be included in the EIIS database [unless is it reported by a non-registrant (e.g., an 

incident submitted by a state agency – which are not systematically collected)]. Therefore, 

because the number of documented kills in EIIS is believed to be a small fraction of total 

mortality caused by pesticides, absence of reports does not necessarily provide evidence of an 

absence of incidents. 
-27 of 31-

Appendix B. The Risk Quotient Method and Levels of Concern 

The Risk Quotient Method is the means used by EFED to integrate the results of exposure and 

ecotoxicity data. For this method, Risk Quotients (RQs) are calculated by dividing exposure 

estimates by the acute and chronic ecotoxicity values (i.e., RQ = EXPOSURE/TOXICITY). 

These RQs are then compared to OPP's levels of concern (LOCs). These LOCs are criteria used 

by OPP to indicate potential risk to non-target organisms and the need to consider regulatory 

action. EFED has defined LOCs for acute risk, potential restricted use classification, and for 

endangered species. 

The criteria indicate that a pesticide used as directed has the potential to cause adverse effects 

on non-target organisms. LOCs currently address the following risk presumption categories: 

(1) acute - there is a potential for acute risk; regulatory action may be warranted in addition to 

restricted use classification; 

(2) acute restricted use - the potential for acute risk is high, but this may be mitigated through 

restricted use classification;

(3) acute endangered species - the potential for acute risk to endangered species is high, 

regulatory action may be warranted; and 

(4) chronic risk - the potential for chronic risk is high, regulatory action may be warranted. 

Currently, EFED does not perform assessments for chronic risk to plants, acute or chronic 

risks to non-target insects, or chronic risk from granular/bait formulations to mammalian or 

avian species. 

The ecotoxicity test values (i.e., measurement endpoints) used in the acute and chronic RQs are 

derived from required studies. Examples of ecotoxicity values derived from short-term 

laboratory studies that assess acute effects are: (1) LC50 (fish and birds), (2) LD50 (birds and 

mammals), (3) EC50 (aquatic plants and aquatic invertebrates), and (4) EC25 (terrestrial 

plants). Examples of toxicity test effect levels derived from the results of long-term laboratory 

studies that assess chronic effects are: (1) the Lowest Observed Adverse Effect Concentration 

(LOAEC) (birds, fish, and aquatic invertebrates), and (2) the No Observed Adverse Effect 

Concentration (NOAEC) (birds, fish and aquatic invertebrates). The NOAEC is generally used 

as the ecotoxicity test value in assessing chronic effects. Risk presumptions, along with the 

corresponding RQs and LOCs are summarized in Table B1.
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Table B1. Agency risk quotient (RQ) metrics and levels of concern (LOC) per risk class.

Risk Class Risk Description RQ LOC

Aquatic Animals (fish and invertebrates)

Acute Potential for effects to non-listed animals from acute 

exposures

Peak EEC/LC501 0.5

Acute 

Restricted Use

Potential for effects to animals from acute exposures

Risks may be mitigated through restricted use classification

Peak EEC/LC501 0.1

Acute Listed 

Species

Listed species may be potentially affected by acute 

exposures

Peak EEC/LC501 0.05

Chronic Potential for effects to non-listed and listed animals from 

chronic exposures 

60-day EEC/NOEC (fish) 1

21-day EEC/NOEC (invertebrates)

Terrestrial Animals (mammals and birds)

Acute Potential for effects to non-listed animals from acute 

exposures

EEC2/LC50 (Dietary) 0.5

EEC/LD50 (Dose)

Acute 

Restricted Use

Potential for effects to animals from acute exposures

Risks may be mitigated through restricted use classification

EEC2/LC50 (Dietary) 0.2

EEC/LD50 (Dose)

Acute Listed 

Species

Listed species may be potentially affected by acute 

exposures

EEC 2/LC50 (Dietary) 0.1

EEC/LD50 (Dose)

Chronic Potential for effects to non-listed and listed animals from 

chronic exposures

EEC 2/NOAEC 1

Plants

Non-Listed Potential for effects to non-target, non-listed plants from 

exposures

EEC/ EC25 1

Listed Plant Potential for effects to non-target, listed plants from 

exposures

EEC/ NOEC 1

EEC/ EC05

1 LC50 or EC50. 2 Based on upper bound Kenaga values.
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Appendix C. STIR Input/Output

Welcome to the EFED 

Screening Tool for Inhalation Risk

This tool is designed to provide the risk assessor with a rapid method for determining 

the potential

significance of the inhalation exposure route to birds and mammals in a risk 

assessment.

Input

Application and Chemical Information

Enter Chemical Name heptyl

Enter Chemical Use dog repellent

Is the Application a Spray? (enter y or n) n

If Spray What Type (enter ground or air) ground

Enter Chemical Molecular Weight (g/mole) 184.28

Enter Chemical Vapor Pressure (mmHg) 4.09E-03

Enter Application Rate (lb a.i./acre) 0.2134

Toxicity Properties

Bird

Enter Lowest Bird Oral LD50 (mg/kg bw) 0.98

Enter Mineau Scaling Factor 1.15

Enter Tested Bird Weight (kg) 0.178

Mammal

Enter Lowest Rat Oral LD50 (mg/kg bw) 2.45

Enter Lowest Rat Inhalation LC50 (mg/L) 0.00245

Duration of Rat Inhalation Study (hrs) 4

Enter Rat Weight (kg) 0.35

Output

Results Avian (0.020 kg )

Maximum Vapor Concentration in Air at Saturation 

(mg/m3) 4.06E+01

Maximum 1-hour Vapor Inhalation Dose (mg/kg) 5.10E+00

Adjusted Inhalation LD50 5.46E-03

Ratio of Vapor Dose to Adjusted Inhalation LD50 9.33E+02 Proceed to Refinements

Maximum Post-treatment Spray Inhalation Dose 

(mg/kg) not applicable

Ratio of Droplet Inhalation Dose to Adjusted 

Inhalation LD50 not applicable not applicable

Results Mammalian (0.015 kg )
-30 of 31-

Maximum Vapor Concentration in Air at Saturation 

(mg/m3) 4.06E+01

Maximum 1-hour Vapor Inhalation Dose (mg/kg) 6.41E+00

Adjusted Inhalation LD50 1.46E-01

Ratio of Vapor Dose to Adjusted Inhalation LD50 4.39E+01 Proceed to Refinements

Maximum Post-treatment Spray Inhalation Dose 

(mg/kg) not applicable

Ratio of Droplet Inhalation Dose to Adjusted 

Inhalation LD50 not applicable not applicable

Welcome to the EFED 

Screening Tool for Inhalation Risk

This tool is designed to provide the risk assessor with a rapid method for determining 

the potential

significance of the inhalation exposure route to birds and mammals in a risk 

assessment.

Input

Application and Chemical Information

Enter Chemical Name pentyl

Enter Chemical Use dog repellent

Is the Application a Spray? (enter y or n) n

If Spray What Type (enter ground or air) ground

Enter Chemical Molecular Weight (g/mole) 156.23

Enter Chemical Vapor Pressure (mmHg) 1.19E-02

Enter Application Rate (lb a.i./acre) 0.1045

Toxicity Properties

Bird

Enter Lowest Bird Oral LD50 (mg/kg bw) 0.98

Enter Mineau Scaling Factor 1.15

Enter Tested Bird Weight (kg) 0.178

Mammal

Enter Lowest Rat Oral LD50 (mg/kg bw) 2.45

Enter Lowest Rat Inhalation LC50 (mg/L) 0.00245

Duration of Rat Inhalation Study (hrs) 4

Enter Rat Weight (kg) 0.35

Output

Results Avian (0.020 kg )

Maximum Vapor Concentration in Air at Saturation 

(mg/m3) 1.00E+02
-31 of 31-

Maximum 1-hour Vapor Inhalation Dose (mg/kg) 1.26E+01

Adjusted Inhalation LD50 5.46E-03

Ratio of Vapor Dose to Adjusted Inhalation LD50 2.30E+03 Proceed to Refinements

Maximum Post-treatment Spray Inhalation Dose 

(mg/kg) not applicable

Ratio of Droplet Inhalation Dose to Adjusted 

Inhalation LD50 not applicable not applicable

Results Mammalian (0.015 kg )

Maximum Vapor Concentration in Air at Saturation 

(mg/m3) 1.00E+02

Maximum 1-hour Vapor Inhalation Dose (mg/kg) 1.58E+01

Adjusted Inhalation LD50 1.46E-01

Ratio of Vapor Dose to Adjusted Inhalation LD50 1.08E+02 Proceed to Refinements

Maximum Post-treatment Spray Inhalation Dose 

(mg/kg) not applicable

Ratio of Droplet Inhalation Dose to Adjusted 

Inhalation LD50 not applicable not applicable