Page 2 of 12

EXECUTIVE SUMMARY

EPA’s Health Effects Division (HED) has evaluated the available data and the most recent 

human health risk assessments for the repellent furanone to determine the scope of work 

necessary to support the registration review process. Furanone is the common name used to 

describe two active ingredients: dihydro-5-pentyl-2(3H)-furanone and dihydro-5-heptyl-2(3H)-

furanone, also called tanol derivatives. HED has considered the current use patterns (OPPIN 

Database and current labels) as well as the available toxicity and exposure information for 

furanone. The most recent human health risk assessment for furanone was conducted in for the 

Reregistration Eligibility Decision (J. Redden, 09/29/1995). 

The purpose of the scoping process is to present the results of HED’s determination regarding

the sufficiency of available data to assess the safety of this pesticide, including any new data 

submitted since the last assessment that would necessitate conducting a new human health risk 

assessment to support registration review. 

The two furanones addressed in this document are natural occurring compounds found in 

apricots and peaches. In addition, dihydro-5-heptyl-2(3H)-furanone is found in milk and meat 

products, and passion fruit. These are used as fragrances and are registered by the FDA as food 

additives. However, they are not listed as “Generally Recognized as Safe” by the FDA. The 

toxicology database for the furanones does not contain all of the guideline studies required for a 

non-food use; however, the furanones are natural products and approved for uses in foods and 

cosmetics at levels higher than currently allowed in registered pesticide products. 

All the end-use products containing furanones are co-formulated with limonene but the latter is 

addressed separately (G. F. Kramer, D374492, 08/13/2011). Products containing furanones are 

not registered for food uses at this time. Currently, four products containing furanones are 

registered for non-food uses; in two these are included as active ingredients (EPA Reg. No. 

45987-1 and 66617-1) and in two as inert ingredients. 

Since these compounds are widely used as flavoring agents and fragrances, are naturally 

occurring, are present in registered pesticide products at very low levels resulting in very low 

exposures from pesticidal uses, and show minimal toxicity in available toxicity studies, 

additional toxicity and exposure data are not required. Therefore, a quantitative risk assessment 

for pesticide-related uses is not required. 

1.0 FURANONE FORMULATIONS AND USE PATTERNS 

HED used the Biological and Economics Analysis Division (BEAD) Label Data System to 

identify all agricultural and non-agricultural uses of furanone. See Furanone HED Master Label 

Report (11/Mar/2011) for a complete list. The concentrations of the active ingredients in the 

end-use products are: 0.024% for dihydro-5-pentyl-2(3H)-furanone and 0.049% for dihydro-5-

heptyl-2(3H)-furanone. Formulations containing the furanones as the active ingredient include 

(1) a granular dog and cat repellent and (2) an insect repellent wrist and ankle band. In addition,
Page 3 of 12

two formulations including the furanones as inert ingredients were identified by the Pesticide 

Reregistration Division. These are discussed in the Confidential Appendix.

Agricultural Uses

End-use products containing furanones are not registered for agricultural uses at this time.

Non-Agricultural and Residential Uses

Pesticide products for residential uses containing furanones as active ingredients and inerts are 

listed in Appendix B.

2.0 HAZARD IDENTIFICATION/TOXICOLOGY

Although not being an FDA GRAS chemical, the furanones are approved as food additives at 

levels up to 0.2% since they are naturally occurring compounds and exposures to low 

concentrations are considered safe at comparable concentrations of furanones used in cosmetic 

products (lotions, detergents, perfumes). Furanone pesticide products have maximum 

concentrations of 0.05%. 

The acute toxicity results are classified as low-toxicity (Category IV) for the furanone 

formulations. However, the acute toxicity studies for the furanones were conducted on products 

also containing limonene. 

Table 1. Acute toxicity studies for an animal repellent end-use product1 containing the 

furanones2 and limonene.

 Test Results Category

Oral LD50--rat LD50 > 5 gm/kg IV

Dermal LD50--rabbit LD50 of dry formulation > 5 gm/kg IV

Inhalation LC50--rat LC50 > 5 mg/l, using particle size of 297 

microns or less.

IV

Eye irritation--rabbit PIS - Washed = 0.0. PIS -Unwashed = 0.0 IV

Dermal irritation--rabbit PIS = 0.0 IV

Dermal sensitization--Guinea pig No sensitization using draize technique ----

1 From a monogram of animal repellent # 100 (J. Redden, 09/29/1995). 2 Percent of the furanones in the end-use product: 0.024% for dihydro-5-pentyl-2(3H)-furanone and 0.049% for 

dihydro-5-heptyl-2(3H)-furanone.

The following acute studies were performed with the active ingredient but are based in reports 

from the open literature: 

 
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- For dihydro-5-pentyl-2(3H)-furanone, the acute oral LD50 in rats and guinea pigs was 

reported as 9780 (category III) and 3440 (category IV) mg/kg, respectively (Jenner, 

Hagan, Taylor, Cook & Fitzhugh, 1964). The acute oral LD50 in rats was reported as 

6600 mg/kg (category IV, 5800-7400 mg/kg, Moreno, 1972a). The acute dermal LD50 in 

rabbits exceeded 5000 mg/kg (category IV, Moreno, 1972b). Dihydro-5-pentyl-2(3H)-

furanone applied full strength to intact or abraded rabbit skin for 24 hr under occlusion 

was slightly irritating (Moreno 1973b).

- For dihydro-5-heptyl-2(3H)-furanone, the acute oral LD50 in rats was reported as 18500 

mg/kg (category IV, Jenner, Hagan, Taylor, Cook & Fitzhugh. 1964). Fatty infiltration 

of liver parenchymal cells occurred in rats fed 13-115 mg dihydro-5-heptyl-2(3H)-

furanone for 5-9 days (Shillinger, 1950).

In sub-chronic studies, administration of dihydro-5-heptyl-2(3H)-furanone and dihydro-5-pentyl2(3H)-furanone to rats for 90 days at levels in excess of at least 100 times the maximum 

estimated daily dietary intake in man evoked no adverse effect on growth, food consumption, 

haematology, blood chemistry, liver and kidney weights or on gross and microscopic appearance 

of major organs at autopsy. When fifteen FDRL rats were fed at 14.6 and 62.8 mg/kg/day for 90 

days, no significant gross pathological change was observed at autopsy in any rats. Several of the 

animals in the groups receiving the lactones showed various degrees of mild thyroid hyperplasia 

but this observation was also noted in the corresponding control groups and is not an uncommon 

finding in these laboratories (Food Cosmet. Toxicol. Vol. 3, pp. 563-569. Pergamon Press 1965).

In chronic studies, dihydro-5-pentyl-2(3H)-furanone at 0.1-0.5% fed to groups of 20 male and 

female rats in the diet for 2 years produced no effects. For dihydro-5-heptyl-2(3H)-furanone, 

groups of 20 male and 20 female rats were fed diets containing 0.1 or 0.5% dihydro-5-heptyl2(3H)-furanone for 2 years without any specific adverse effects. Both furanones in feeding 

studies at 0.1-0.5% for two years were reported to produce no effects with respect to 

carcinogenicity (Bar & Griepentrog, 1967; Food Cosmet. Toxicol. Vol. 12, pp 889 and 921, 

1975). 

Conclusion

The toxicology database for the furanones does not contain standard Part 158 guideline studies; 

the bulk of the toxicology investigations on the furanones are through the open literature. 

However, the furanones are natural products and approved for uses in foods and cosmetics at 

levels higher than currently registered pesticide products. Based on the summary listed in the 

1995 RED that the hazard of the furanones is limited, HED concludes that additional toxicity 

data are not required, and that a quantitative risk assessment for pesticide-related uses is not 

required. 

3.0 RESIDUE CHEMISTRY

The furanones are not currently registered as a pesticide for uses in food commodities; therefore, 

evaluation of residues in crops is not needed.
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4.0 DIETARY EXPOSURE

The furanones are not currently registered for food-uses in agricultural commodities. Turf uses 

of the cat & dog repellent granule formulation may be assessed for residues in drinking water. 

However, the furanones are not soluble in water, are naturally occurring, are widely used as food 

additives and fragrances, are present in registered pesticide products at very low levels resulting 

in significant exposures from pesticide uses, and show minimal toxicity in available toxicity 

studies. Based on this a dietary exposure assessment is not required for registration review. 

5.0 TOLERANCE ASSESSMENT AND INTERNATIONAL HARMONIZATION

Tolerances are not established for furanones since no registered pesticide uses in food

commodities exist at this time.

6.0 RESIDENTIAL EXPOSURE

Residential Handler and Post-application Exposure

The products containing furanones as the active ingredient include cat and dog repellent 

granules, and impregnated materials (wrist and ankle bands). Moreover, two products containing 

the furanone as inerts are registered at this time. Residential exposure was not previously 

quantitatively assessed for either active or inert uses of the furanones. Since these compounds 

are widely used as food additives and fragrances, are naturally occurring, are present in 

registered pesticide products at very low levels and likely to result in very low exposures from 

pesticidal uses, as well as showing minimal toxicity in available toxicity studies, a quantitative 

residential handlers and postapplication exposure assessment is not required. 

7.0 AGGREGATE EXPOSURE AND RISK ASSESSMENT

In accordance with FQPA, HED considers and aggregates pesticide exposures and risks from 

three major sources: food, drinking water, and residential exposures. In an aggregate 

assessment, exposures from dietary and residential sources are added together and compared to 

quantitative estimates of hazard (e.g., a NOAEL), or the risks themselves can be aggregated. 

Since quantitative risk assessments are not required for the furanones, an aggregate assessment is 

not needed for registration review. 

8.0 OCCUPATIONAL EXPOSURE 

There is potential for occupational handler and postapplication exposure to furanone. However, 

a quantitative assessment for these uses in pesticide products was not previously performed and 

is still not required for the same rationale stated for the residential exposure section. 
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9.0 PUBLIC HEALTH AND PESTICIDE EPIDEMIOLOGY DATA

K. Swe Oo, D393554, 09/07/2011

The OPP Incident Data System (IDS) was utilized for pesticide incident data on the active 

ingredient furanone (PC Code 122301, 122302). The purpose of the database search is to 

identify potential patterns on the frequency and severity of the health effects attributed to

furanones exposure. The IDS includes reports of alleged human health incidents from various 

sources, including mandatory Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) 

Section 6 (a) (2) reports from registrants, other federal and state health and environmental 

agencies and individual consumers. Since 1992, OPP compiles these reports in IDS. The IDS 

contains reports from across the U.S. and most incidents have all relevant product information 

recorded. Reports submitted to the IDS represent anecdotal reports or allegations only, unless 

otherwise stated in the report. 

IDS records incidents resulting in higher severity outcomes in more detail in a module called the 

Main IDS module. This system stores incident data for death, major and moderate incidents, and 

it includes more details about the location, date and nature of the incident. Main IDS incidents 

involving only one pesticide are considered to provide more certain information about the 

potential effects of exposure from the pesticide. The less severe human incidents (minor, 

unknown, or no effects outcomes) are reported by registrants as counts called aggregate 

summaries and are recorded in a separate module called Aggregate IDS. 

In Aggregate IDS, from January 1, 2006 to April 26, 2011, there are 116 incidents involving 

pesticide products containing the furanones. Because it falls within the categories reported as 

counts (which includes minor, unknown or no effects), there is no unique report that provides 

details about the incident and single chemical incidents are not distinguished from multiple 

chemical incidents; however, a high frequency of incidents indicates there is a high potential for 

exposure and vice versa. For furanones, there appears to be some potential for exposure. 

For the Main IDS, from January 1, 2006 to April 26, 2011, there are 10 cases reported that 

involve pesticide products containing the furanones as one of the active ingredients in the 

product. There are 5 cases in 2006, 3 cases in 2007 and one case each in 2008 and 2010.

However, there is no case reported for single chemical furanone only in the database, since all 

furanone products are co-formulated with other ingredients. 

Another system used by HED to search for human incidents with pesticides is the Agricultural 

Health Study (AHS). The AHS is a high quality, prospective epidemiology study evaluating the 

link between pesticide use and various health outcomes including cancer. Furanones are not 

included in the AHS.

Conclusions 

Based on the low frequency and severity of incident cases, there does not appear to be a concern 

at this time that would warrant further investigation. The Agency will continue to monitor the 

incident information and if a concern is triggered, additional analysis will be included in the risk 

assessment.
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10.0 ENVIRONMENTAL JUSTICE

Potential areas of environmental justice concerns, to the extent possible, will be considered in 

future human health risk assessments for furanone, in accordance with U.S. Executive Order 

12898, "Federal Actions to Address Environmental Justice in Minority Populations and LowIncome Populations," 

http://www.epa.gov/compliance/resources/policies/ej/exec_order_12898.pdf. The Office of 

Pesticide Programs (OPP) typically considers the highest potential exposures from the legal use 

of a pesticide when conducting human health risk assessments, including, but not limited to, 

people who obtain drinking water from sources near agricultural areas, the variability of diets 

within the U.S., and people who may be exposed when harvesting crops. Should these highest 

exposures indicate potential risks of concern, OPP further refines the risk assessments to ensure 

that the risk estimates are based on the best available information.

11.0 CUMULATIVE RISK ASSESSMENT

EPA does not have, at this time, available data to determine whether furanone has a common 

mechanism of toxicity with other substances or how to include this pesticide in a cumulative risk 

assessment. Therefore, EPA has not assumed that furanone has a common mechanism of 

toxicity with other substances and a cumulative risk assessment is not anticipated at this time.

12.0 ENDOCRINE DISRUPTOR SCREENING PROGRAM

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

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

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

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

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

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

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

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

taxonomic groups. 

EPA has developed the Endocrine Disruptor Screening Program (EDSP) to determine whether 

certain substances (including pesticide active and other ingredients) may have an effect in 

humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or other such 

endocrine effects as the Administrator may designate.” The EDSP employs a two-tiered 

approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 

screening assays to identify the potential of a chemical substance to interact with the estrogen, 

androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening 

and are found to have the potential to interact with E, A, or T hormonal systems will proceed to 

the next stage of the EDSP where EPA will determine which, if any, of the Tier 2 tests are 

necessary based on the available data. Tier 2 testing is designed to identify any adverse 

endocrine-related effects caused by the substance, and establish a dose-response relationship 
Page 8 of 12

between the dose and the E, A, or T effect. 

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

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

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. Furanones are 

not among the group of 58 pesticide active ingredients on the initial list to be screened under the 

EDSP. Accordingly, as part of registration review, EPA will issue future EDSP orders/data callins, requiring the submission of EDSP screening assays for Furanones. For further information 

on the status of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the 

test guidelines and the Tier 1 screening battery, please visit our website: 

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

13.0 HUMAN STUDIES

Studies in which adult human subjects were intentionally exposed to furanones to determine their 

dermal and inhalation exposure haven’t been used to address human health risk assessments on 

these chemicals. 

14.0 DATA REQUIREMENTS

Data requirements for conventional pesticides will be waived for the furanones based on the 

afore mentioned characteristics of these chemicals and the end-use products containing them.

15.0 REFERENCES

 

Redden, J. C., 09/29/1995. The HED Chapter of the Re-registration Eligibility Decision 

Document (RED) for Dihydro-5-Pentyl-2(3H)-Furanone (PC Code: 122301) and 5-

Heptyldihydro-2(3H)-Furanone (PC Code: 122302) Case no. 3138: Tanol Derivatives.

Swe Oo, D393554, 09/07/2011. Tanol derivatives: Review of Human Incidents.

G. F. Kramer, A. Nowotarski, R. Mitkus, D374492, 08/13/2010. D-Limonene. Human Health 

Assessment Scoping Document in Support of Registration Review. 

Bar, F. and Griepentrog, F. (1967) Die Situation in der gesundheitlichen Beurteilung der 

Aromatisierungsmittel fur Lebensmittel. Medizin Ernahr. 8: 244. 

Food Cosmet. Toxicol. Vol. 3, pp. 563-569. Pergamon Press 1965.

Food Cosmet Toxicol Vol. 12, pp. 889 and 921. Pergamon Press 1975.

Food and Cosmetics Toxicology Volume 13, 921, 1975
Page 9 of 12

Appendix A: Chemistry

1.0 PHYSICAL/CHEMICAL PROPERTIES CHARACTERIZATION

The two furanones addressed in this document are natural occurring compounds found in 

apricots and peaches. In addition, dihydro-5-heptyl-2(3H)-furanone is found in milk and meat 

products, and passion fruit. These are used as fragrance and are registered by the FDA as food 

additives. However, they are not listed as “Generally Recognized as Safe” by the FDA. 

1.1 Identification of Active Ingredient

Chemical Name: Dihydro-5-heptyl -2(3H)-furanone

Common Name: gamma- Undecalactone

Chemical Type: Repellent

PC Code Number: 122302

CAS Registry No.: 104-67-6

Empirical Formula: C11H20O2

Molecular Weight: 184.31

Chemical Name: Dihydro-5-pentyl-2(3H)-furanone

Common Name: gamma-Nonalactone

Chemical Type: Repellent

PC Code Number: 122301

CAS Registry No.: 104-61-0

Empirical Formula: C9H16O2

Molecular Weight: 156.25

1.2 Structural Formula of the Furanones

Dihydro-5-heptyl -2(3H)-furanone Dihydro-5-pentyl-2(3H)-furanone
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1.3 Physical and Chemical Properties

Chemical 

Name:

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

Color: colorless to yellow colorless to yellow

Odor: strong fruity odor suggestive of peach strong odor suggestive of coconut

Melting point: liquid, not applicable liquid, not applicable

Solubility: 60% alcohol in water - 20% soluble

70% alcohol in water - 33% soluble

Insoluble in water

50% alcohol in water - 20% soluble

60% alcohol in water - 33% soluble

Insoluble in water

Stability: stable under all normal conditions stable under all normal conditions

Octanol/water 

partition 

coefficient:

not available not available

Physical state: liquid liquid

Density: 0.942 - 0.945 0.958 - 0.966

Boiling Point not available 243 C

Vapor 

Pressure:

not available not available

pH: not available not available
Page 11 of 12

Appendix B: Furanone Products

PRD Appendix A: Food/Feed & Non –Food/Non-Feed Uses Considered in Registration Review (03/11/2011) Partial Report Food (F) / Non-food (N)

Use Site

Formulation 

Description1

Application 

Method/ Type

Application 

Method/ 

Equipment

Product Max 

App Rate

A. I. Max App 

Rate Max # Apps / Year

Products with Furanones as Active Ingredients

N

HOUSEHOLD/

DOMESTIC DWELLINGS 

OUTDOOR PREMISES

66617-1

(IMPR)

Insecticidal 

strip treatment

Impregnated 

strip

NS NS NS

HUMAN BODY/CLOTHING 

WHILE BEING WORN

Clothing 

treatment Cloth NS NS NS

Skin contact 

treatment Ankle band NS NS NS

Skin contact 

treatment. Wrist band NS NS NS

N ORNAMENTAL HERBACEOUS 

PLANTS,Turf 45987-1 (G) Spreader Not on label 1 lb/ 100 sq ft 0.104 lb ai / A NS

1 Concentration of the active ingredients: 0.024% dihydro-5-pentyl-2(3H)-furanone and 0.049% dihydro-5-heptyl-2(3H)-furanone. 2 NS = Not Specified
Page 12 of 12

CONFIDENTIAL APPENDIX

Appendix C: Products containing the furanones as inerts

Two formulations including the furanones as inert ingredients were identified by the Pesticide Reregistration Division, see table 

below. Food (F) / Non-food (N)

Use Site

Formulation 

Description

Application 

Method/ Type

Application 

Method/ 

Equipment

Product Max 

App Rate Max # Apps / Year

Products with Furanones as Inactive Ingredients

N Rodspray Fly, Crockroach & Ant 

Killer 45987-2 Spray treatment Spray NS NS

N Rodspray Indoor-Outdoor 

Crawling Insect Killer 45987-9 Spray treatment Spray NS NS

NS = Not Specified