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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF

CHEMICAL SAFETY AND

POLLUTION PREVENTION

MEMORANDUM

Date: 08-MAY-2013

SUBJECT: Fenpyroximate. Human-Health Risk Assessment for Proposed Section 3 Uses 

on Stone Fruits (Group 12-12), Tuberous and Corm Vegetables (Subgroup 1C), 

and Small Vine Climbing Fruits Except Kiwifruit (Subgroup 13-07F).

PC Code: 129131 DP Barcode: D404839

Decision No.: 468635 Registration Nos.: 71711-4 and 71711-19

Petition No.: 2E8072 Regulatory Action: Section 3 Registration

Risk Assessment Type: Single Chemical/Aggregate Case No.: 7432

TXR No.: NA CAS No.: 134098-61-6 (E-isomer)

MRID No.: NA 40 CFR: §180.566

FROM: Jennifer R. Tyler, Chemist

George F. Kramer, Ph.D., Senior Chemist

Chester E. Rodriguez, Ph.D., Toxicologist

Risk Assessment Branch 1 (RAB1)

Health Effects Division (7509P)

THROUGH: Charles W. Smith III, Acting Branch Chief

RAB1/HED (7509P)

TO: Sydney Jackson/Barbara Madden, RM 05

Registration Division (RD; 7505P)

The HED of the Office of Pesticide Programs (OPP) is charged with estimating the risk to human 

health from exposure to pesticides. The RD of OPP has requested that HED evaluate hazard and 

exposure data and conduct dietary, occupational/residential, and aggregate exposure assessments, 

as needed, to estimate the risk to human health that will result from the registered and proposed 

uses of the insecticide/miticide fenpyroximate ((E)-1,1-dimethylethyl 4-[[[[(1,3-dimethyl-5-

phenoxy-1H-pyrazol-4-yl)methylene]amino]oxy]methyl]benzoate). A summary of the estimated 

human health risks resulting from the registered and requested fenpyroximate uses are provided 

in this document. The risk assessment and occupational/residential exposure assessment were 

provided by Jennifer Tyler (RAB1); the residue chemistry data review and dietary exposure 

assessment by George Kramer (RAB1); the hazard characterization by Chester Rodriguez 

(RAB1); and the drinking water assessment by Greg Orrick of the Environmental Fate and 

Effects Division (EFED).
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TABLE OF CONTENTS

1.0 Executive Summary............................................................................................................. 3

2.0 HED Recommendations....................................................................................................... 7

2.1 Data Deficiencies ............................................................................................................. 7

2.2 Tolerance Considerations................................................................................................. 7

2.2.2 Recommended Tolerances............................................................................................ 8

2.3 Label Recommendations.................................................................................................. 8

3.0 Introduction.......................................................................................................................... 9

3.1 Chemical Identity ............................................................................................................. 9

3.2 Physical/Chemical Characteristics................................................................................... 9

3.3 Pesticide Use Pattern........................................................................................................ 9

3.4 Anticipated Exposure Pathways..................................................................................... 11

3.5 Consideration of Environmental Justice ........................................................................ 11

4.0 Hazard Characterization and Dose-Response Assessment................................................ 11

4.1 Hazard Profile ................................................................................................................ 11

4.4 Safety Factor for Infants and Children (FQPA Safety Factor)....................................... 13

5.0 Dietary Exposure and Risk Assessment ............................................................................ 17

5.1 Residues of Concern Summary and Rationale............................................................... 17

5.2 Food Residue Profile...................................................................................................... 18

5.3 Water Residue Profile .................................................................................................... 18

5.4 Dietary Risk Assessment................................................................................................ 19

6.0 Residential (Non-Occupational) Exposure/Risk Characterization .................................... 20

6.1 Residential Bystander Post-Application Inhalation Exposure ....................................... 20

6.2 Spray Drift...................................................................................................................... 21

7.0 Aggregate Exposure/Risk Characterization....................................................................... 21

7.1 Acute Aggregate Risk .................................................................................................... 21

7.2 Chronic Aggregate Risk................................................................................................. 22

8.0 Cumulative Exposure/Risk Characterization..................................................................... 22

9.0 Occupational Exposure/Risk Characterization .................................................................. 22

9.1 Handler Exposure/Risk Estimates................................................................................. 22

9.2 Post-Application Exposure/Risk Estimates................................................................... 26

10.0 References.......................................................................................................................... 28

Appendix A. Toxicology Profile Tables...................................................................................... 30

Appendix B. Physical/Chemical Properties................................................................................. 34
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1.0 Executive Summary

Fenpyroximate is a contact insecticide/miticide used for the control of leafhoppers, mealybugs, 

and mites. Fenpyroximate is a mitochondrial electron-transport inhibitor (METI) which acts by

targeting proton-translocating NADH:Q oxidoreductase and blocking ubiquinone reduction.

The Interregional Project No. 4 (IR-4) has proposed a Section 3 Registration for application of 

fenpyroximate to stone fruits (group 12-12), small vine climbing fruits except kiwifruit 

(subgroup 13-07F), and tuberous and corm vegetables (subgroup 1C). IR-4, on behalf of the 

Agricultural Experiment Stations of CA, MI, MT, PA, TX, and UT, requests the establishment of 

tolerances for the combined residues of the insecticide fenpyroximate, including its metabolites 

and degradates, in or on the commodities in the table below. Compliance with the tolerance 

levels specified below is to be determined by measuring only the sum of fenpyroximate, (E)-1,1-

dimethylethyl 4-[[[[(1,3-dimethyl-5-phenoxy-1H-pyrazol-4-yl) methylene] amino]oxy]methyl] 

benzoate and its Z-isomer, (Z)-1,1-dimethylethyl 4-[[[[(1,3-dimethyl-5- phenoxy-lH-pyrazol-4-

yl) methylene]amino]oxy] methyl]benzoate, calculated as the stoichiometric equivalent of 

fenpyroximate, in/on the following raw agricultural commodities (RACs): fruit, stone, group 12 

at 2.0 ppm; vegetable, tuberous and corm, subgroup 1C at 0.10 ppm; and fruit, small, vine 

climbing, except fuzzy kiwifruit, subgroup 13-07F at 1.0 ppm.

Fenpyroximate tolerances have been established in 40 CFR §180.566. Tolerances for plant 

commodities are expressed in terms of combined residues of fenpyroximate and its Z-isomer. 

Permanent tolerances for plant commodities, under §180.566(a)(1) range from 0.10 ppm for 

cotton undelinted seed to 20 ppm for tea. Tolerances for milk and the fat, meat, and meat 

byproducts (excluding liver and kidney) of cattle, goat, horse, and sheep are listed in 40 CFR 

§180.566(a)(2) and are expressed in terms of the combined residues of fenpyroximate and its 

metabolites (E)-4-[(1,3-dimethyl-5-phenoxypyrazol-4-yl)-methylene aminooxymethyl]benzoic 

acid and (E)-1,1-dimethylethyl-2-hydroxyethyl 4-[[[[(1,3-dimethyl-5-phenoxy-1H-pyrazol-4-

yl)methylene]amino]oxy]methyl]benzoate, calculated as the parent compound. Tolerances for 

cattle, goat, horse, and sheep liver and kidney are listed under 40 CFR §180.566(a)(3) at 0.25 

ppm and are expressed in terms of fenpyroximate and its metabolite (E)-4-[(1,3-dimethyl-5-

phenoxypyrazol-4-yl)-methylene aminooxymethyl]benzoic acid, calculated as the parent 

compound. A time-limited tolerance for residues in/on honey at 0.10 ppm with a 12/31/13 

expiration date is listed in 40 CFR §180.566(b) under a Section 18 Emergency Exemption. 

Fenpyroximate has no uses that result in residential exposure. 

Toxicity Profile: Fenpyroximate was classified as Category II for acute toxicity via the oral and 

inhalation routes of exposure. It exhibited low dermal acute toxicity (Category III) and was 

neither a skin nor eye irritant. Fenpyroximate is considered to be a slight to moderate skin 

sensitizer.

The effects following repeated oral exposures to fenpyroximate were based on systemic toxicity

(no specific target organ/tissue identified). The most sensitive species tested was the dog. The 

effects reported in the dog included slight bradycardia, deficits in food consumption, body

weight, body-weight gain, and an increased incidence of emesis and diarrhea. Emaciation and 

torpor (sluggish inactivity) were reported in female dogs at lower dose levels than males. The 

highest dose tested in the dog (50 mg/kg bw/day) resulted in first- and second-degree heart 
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block, increased urea concentration, decreased glucose, and altered plasma electrolyte levels 

among other signs of toxicity. In subchronic and chronic studies with rats, the primary effect 

was decreased body-weight gain in both sexes with hematological changes (e.g., higher counts of 

red blood cells) at higher doses.

In a rat prenatal developmental toxicity study, a dose level that marginally affected maternal 

body weight and food consumption also resulted in an increased litter incidence of increased 

thoracic ribs, indicating increased prenatal (qualitative) susceptibility. In the rabbits, there were 

no developmental effects reported at the levels tested. In the rat two-generation reproductive 

toxicity study; maternal toxicity (decreased body weight) and offspring toxicity (decreased 

lactational weight gain in both generations) occurred at the same dose.

There is no evidence that fenpyroximate specifically targets the nervous or immune system based 

on the results of recently submitted studies. In the acute neurotoxicity study, neurotoxicity signs 

such as decreases in motor activity occurred in the presence of other effects including decreases 

in body weight and food consumption, and in the absence of neuropathology. Similar results 

were noted in a delayed acute neurotoxicity study in the hen where no effects (neurotoxic or 

otherwise) were reported. The results of the rat subchronic neurotoxicity study did not indicate 

any neurotoxicity-specific effects; deficits in body weight and food consumption were the main 

effects reported. Similarly, the effects reported in a rat immunotoxicity study were limited to 

decreased body-weight gain.

In a 21-day dermal toxicity study in rats, there were clinical signs in females consisting of red 

nose and mouth/nasal discharge, decreased body weights, body-weight gains, and food 

consumption in males and females. There were also increased liver weights and hepatocellular 

necrosis reported in females.

In a 4-week rat inhalation study, treatment-related effects included clinical observations (labored 

breathing and rales), increased lung weights, decreases in body-weight gain and food 

consumption, and changes in hematology parameters (increased counts of erythrocytes and 

leukocytes). There were also histopathology findings in the nasal passage mucosa consisting of 

atrophy and squamous metaplasia.

Fenpyroximate was classified as “not likely to be carcinogenic to humans” based on the results 

of rat and mouse carcinogenicity studies. Genotoxicity studies including mutagenicity did not 

demonstrate any genotoxic potential associated with fenpyroximate.

Dose-response and Food Quality Protection Act (FQPA) Assessment: The existing toxicology

database for fenpyroximate is complete and adequate for FQPA evaluation, risk assessment, and 

tolerance setting. Appropriate endpoints were identified for exposures to fenpyroximate. For the 

acute dietary risk assessment of females 13-49 years old, the acute population-adjusted dose 

(aPAD) of 0.05 mg/kg/day was selected based on the no-observed-adverse-effect level (NOAEL) 

of 5.0 mg/kg/day in the rat prenatal developmental toxicity study where an increased incidence 

of additional thoracic ribs was observed at 25.0 mg/kg/day. For the acute dietary risk assessment 

for the general population, the aPAD of 0.375 mg/kg/day was selected based on the NOAEL of 

37.5 mg/kg/day in the rat acute neurotoxicity study where decreases in motor activity and 

auditory startle response were observed. The chronic dietary endpoint for all populations was 
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based on a chronic population-adjusted dose (cPAD) of 0.05 mg/kg/day based on the NOAEL of 

5.0 mg/kg/day in a chronic dog study where an increased incidence of bradycardia and diarrhea 

was observed along with decreases in cholesterol, body-weight gain, and food consumption at 

15.0 mg/kg/day.

For occupational exposure scenarios involving dermal exposure (short- and intermediate-term), a 

route-specific study was selected where decreases in body weight, body-weight gain, and food 

consumption were noted along with increased absolute liver weight and a possible increase in 

hepatocellular necrosis. The dermal NOAEL was chosen as 300 mg/kg/day and the level of 

concern (LOC) is 100. A route-specific inhalation study was used for assessing inhalation 

occupational exposures (short- and intermediate-term). The effects reported included clinical 

observations (labored breathing and rales), increased lung weights, decreases in body-weight 

gain and food consumption, and changes in hematology parameters (increased counts of 

erythrocytes and leukocytes), and histopathology changes. The inhalation NOAEL was chosen 

as 0.002 mg/L and the LOC is 30 because the animal inhalation exposure POD was converted to 

a human-equivalent concentration (HEC) which includes a dosimetry adjustment factor for 

duration of exposure and species differences in respiration and respiratory tract surface area.

The fenpyroximate risk assessment team has evaluated the hazard and exposure data; and, based 

on these data, recommended that the FQPA Safety Factor (SF) be reduced to 1x for all exposure 

scenarios. The recommendation is based on the following: (1) the existing toxicology database 

for fenpyroximate is complete and adequate for FQPA evaluation; (2) there is no concern for 

neurotoxicity; (3) although there was evidence for increased (qualitative) prenatal susceptibility

following oral exposures in the rat developmental toxicity study, the concern is low because 

there was clear NOAEL established; and (4) there are no residual uncertainties with respect to 

exposure data.

Residue Chemistry and Drinking Water Assessments: The residue chemistry and drinking 

water databases are adequate to assess potential human exposure to fenpyroximate. Adequate 

residue chemistry data have been submitted to support the proposed uses. No new residue data 

were submitted to support the tolerance on small vine climbing fruits except kiwifruit (subgroup 

13-07F). IR-4 has requested that the established tolerance for residues in/on grape be expanded 

to its respective crop group. EFED provided Tier 1 estimated drinking water concentrations 

(EDWCs) for fenpyroximate and its isomers/degradates, M1 and M3. The ground water EDWC 

was determined using the Screening Concentration In Ground Water (SCI-GROW) model; and 

surface water EDWCs were determined using the FQPA Index Reservoir Screening Tool 

(FIRST) model and a Provisional Cranberry Model. Surface water EDWCs of 0.043 ppm and 

0.0086 ppm were used in the acute and chronic analyses, respectively, as these values were the 

highest and provided a more conservative approach.

Dietary Risk Estimates (Food + Drinking Water): Acute and chronic aggregate dietary (food + 

drinking water) exposure and risk assessments were conducted for fenpyroximate using the 

Dietary Exposure Evaluation Model - Food Consumption Intake Database (DEEM-FCID, ver. 

3.16) which incorporates consumption data from United States Department of Agriculture 

(USDA) National Health and Nutrition Examination Survey, What We Eat in America, 

(NHANES/WWEIA; 2003-2008). The acute and chronic analyses employed tolerance-level 

residues for all commodities; 100% crop treated (CT) information; DEEM (ver. 7.81) default 
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processing factors (as necessary); and empirical processing factors for several commodities. 

Drinking water was incorporated directly into the dietary assessments using the EDWCs for 

surface water. 

Separate acute dietary exposure and risk analyses were conducted for females 13-49 years old 

and for the general U.S. population as separate endpoints of concern attributable to a single dose 

were identified. The acute dietary risk estimate is not of concern to HED (<100% of the aPAD) 

for females 13-49 years old, or the general U.S. population. The resulting acute risk estimate is 

13% of the aPAD at the 95th percentile of the exposure distribution for females 13-49 years old. 

The highest acute exposure estimate for the U.S. population or population subgroup is children 

1-2 years old, which resulted in a risk estimate of 6.2% of the aPAD.

A chronic dietary exposure and risk assessment was conducted for the general U.S. population 

and various population subgroups. The chronic dietary risk estimates are below HED’s LOC 

(<100% of the cPAD) for the general U.S. population and all population subgroups. The most 

highly exposed population subgroup is children 1-2 years old with a risk estimate of 15% of the 

cPAD.

Residential Exposure: The proposed use is on agricultural crops; therefore, a quantitative 

residential exposure assessment was not conducted. In addition, there are no proposed or 

existing fenpyroximate products registered for residential use sites. 

Aggregate Exposure Assessment: Aggregate exposure risk assessments were assessed by 

incorporating the drinking water directly into the dietary exposure assessment for the following 

scenarios: acute and chronic aggregate exposures (food + drinking water). Short-, intermediate-, 

and long-term aggregate risk assessments were not performed because there are no registered or 

proposed uses of fenpyroximate that result in residential exposures. A cancer aggregate risk 

assessment was not performed because fenpyroximate is not carcinogenic. The acute and 

chronic aggregate risk estimates do not exceed the HED’s LOC for the general U.S. population 

and all population subgroups.

Occupational Exposure: Short- and intermediate-term inhalation and dermal risk estimates for 

handlers were assessed for mixer/loaders and applicators involved in occupational use of 

fenpyroximate. Post-application dermal risk estimates were assessed for workers involved in 

post-application activities. Surrogate data were used to estimate mixer/loader and applicator 

exposure. For handlers, HED has determined that risk estimates are not of concern [margin of 

exposure (MOE) >100 for dermal exposure and >30 for inhalation exposure] at baseline and with 

the addition of gloves (required on the label). HED has also determined that the risk estimates 

are not of concern (i.e., MOE >100) on the day of treatment for all post-application activities. 

Therefore, occupational risk estimates for handlers and post-application workers are not of 

concern.

The proposed labels have a 12-hour restricted-entry interval (REI). Fenpyroximate is classified 

as Toxicity Category II for acute dermal, and Toxicity Category IV for primary eye irritation and 

primary dermal irritation. It is a slight to moderate dermal sensitizer by the maximization test 

method. Therefore, while an assessment of systemic toxicity from post-application exposure 

would indicate acceptable MOEs on the day of treatment, the acute toxicity categories for this 
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chemical require a 24-hour REI for this product under the Worker Protection Standard (WPS). 

RD should ensure that all fenpyroximate labels have the appropriate REI listed. 

The Akari®5SC label should be amended to specify the use of “chemical-resistant gloves” 

instead of “waterproof gloves.” RD should ensure the appropriate personal protective 

equipment (PPE) is listed on the label.

Review of Human Research: This risk assessment relies in part on data from studies in which 

adult human subjects were intentionally exposed to a pesticide or other chemical. These data, 

which include studies from Pesticide Handler Exposure Database (PHED), Version 1.1 (August, 

1998), the AHETF database, the Outdoor Residential Exposure Task Force (ORETF) database, 

and the Agricultural Reentry Task Force (ARTF) database, are subject to ethics review pursuant 

to 40 CFR 26, have received that review, and are compliant with applicable ethics requirements. 

For certain studies, that review may have included reviews by the Human Studies Review Board. 

Descriptions of data sources as well as guidance on their use can be found at 

http://www.epa.gov/pesticides/science/handler-exposure-data.html and 

http://www.epa.gov/pesticides/science/post-app-exposure-data.html.

2.0 HED Recommendations

Provided revised Sections B and F are submitted, HED concludes that the toxicological, residue 

chemistry and occupational/residential databases support a Section 3 registration and 

establishment of the tolerances listed in Section 2.2.2. HED is not recommending for any

additional data in conjunction with this petition.

2.1 Data Deficiencies

No additional data are required to support the proposed use.

2.2 Tolerance Considerations

2.2.1 Enforcement Analytical Method

An adequate enforcement method is available for determination of fenpyroximate residues of 

concern in the proposed/registered crops. A gas chromatography method with 

nitrogen/phosphorus detection (GC/NPD), Method S19, has passed an Agency validation (DP# 

269410, 10/10/00, G. Kramer). Method S19 has a limit of quantitation (LOQ) of 0.05 ppm for 

the combined residues of fenpyroximate and M-1 in snap beans and avocados. A data-gathering 

liquid chromatography/mass spectroscopy/mass spectroscopy (LC/MS/MS) method is also 

available. This method was used for the analysis of the samples from submitted field and 

processing studies.
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2.2.2 Recommended Tolerances

Table 2.2.2. Tolerance Summary for Fenpyroximate.

Commodity Proposed

Tolerance (ppm)

HED-Recommended 

Tolerance (ppm)

Correct Commodity 

Definition/Comments

Fruit, stone, group 12 2.0 2.0 Fruit, stone, group 12-12

Vegetable, tuberous and 

corm, subgroup lC 0.10 0.10

Fruit, small, vine climbing, 

except fuzzy kiwifruit, 

subgroup 13-07F

1.0 1.0

Remove from 40 CFR §180.566 (a)(1):

Grape

2.2.3 Revisions to Petitioned-For Tolerances

A summary of recommended tolerances for the current petition is listed in Table 2.2.2. A 

revised Section F specifying the HED-recommended tolerances should be submitted. 

2.2.4 International Harmonization

Codex and Mexican maximum residue limits (MRLs) are established for residues of 

fenpyroximate per se in/ grapes (fresh and dried). Harmonization with the Codex and Mexican 

MRLs is not possible because the U.S. tolerance expression includes an additional isomer and 

the U.S. use pattern requires a higher numerical value. There are currently no established 

Canadian MRLs.

2.3 Label Recommendations

2.3.1 Recommendations from Occupational Assessment

 The Akari®5SC label should be amended to specify the use of “chemical-resistant 

gloves” instead of “waterproof gloves.” RD should ensure the appropriate PPE is listed 

on the label.

 The acute toxicity categories indicate that a 24-hour REI is appropriate for this product 

under the WPS. The proposed labels list a 12-hour REI. RD should ensure that all 

fenpyroximate labels have the appropriate REI listed.
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3.0 Introduction

3.1 Chemical Identity

Table 3.1. Fenpyroximate Nomenclature.

Chemical structure

Common name Fenpyroximate

Company experimental 

name

NNI-850

IUPAC name tert-butyl(E)-alpha-(1,3-dimethyl-5-phenoxypyrazol-4-ylmethyleneamino-oxy)-p-toluate

CAS name 1,1-dimethylethyl 4-[[[(E)-[(1,3-dimethyl-5-phenoxy1H-pyrazol-4-yl)methylene]-

amino]oxy]methyl]benzoate

CAS registry number 134098-61-6 (E isomer);

111812-58-9 (unspecified stereochemistry) 

End-use products (EPs) FujiMite®/Portal® Miticide/Insecticide 0.4 lb ai/gal EC formulation (5% ai; EPA Reg. No. 71711-19)

Akari®5SC Miticide/Insecticide 0.42 lb ai/gal SC formulation (5% ai; EPA Reg. No. 71711-4)

Chemical structure of 

fenpyroximate Zisomer metabolite

1,1-dimethylethyl 4-[[[(Z)-[(1,3-dimethyl-5-phenoxy1H-pyrazol-4-yl)methylene]-

amino]oxy]methyl]benzoate

Metabolite M1

3.2 Physical/Chemical Characteristics

The physical and chemical properties, as well as a summary of relevant environmental fate 

parameters, are detailed in Appendix B. Fenpyroximate has a low vapor pressure (10-8 mmHg) 

and environmental fate data indicate that it is not likely to volatilize.

3.3 Pesticide Use Pattern

Fenpyroximate is a contact insecticide/miticide used for the control of leafhoppers, mealybugs, 

and mites. U.S. registrations are currently held by Nichino America, Inc., and include 

registrations for nonfood uses on ornamental, floral, and foliage crops, and for several food uses.

The EPs associated with this registration action are Fujimite®5EC Miticide/Insecticide (EPA 

Reg. No. 71711-19), an EC formulation containing 5% ai (equivalent to 0.4 lb ai/gal); Portal®

Miticide/Insecticide (EPA Reg. No. 71711-19), an EC formulation containing 5% ai (equivalent 

to 0.4 lb ai/gal); and Akari®5SC Miticide/Insecticide (EPA Reg. No. 71711-4), an SC 

formulation containing 5% ai (equivalent to 0.42 lb ai/gal). Summaries of the proposed end-use 

products and crop use patterns are presented in Tables 3.3.1 and 3.3.2, respectively.

The proposed FujiMite® 5EC and Portal®labels require applicators and other handlers to wear a 

long-sleeved shirt and long pants, chemical-resistant gloves, protective eyewear, shoes plus 

OCH2

N

N

CH3

H3C C N

O

COOC(CH3)

3

H

COOC(CH3)

3

H

N

N

CH3

H3C C N

O

OCH2
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socks, chemical resistant apron (for mixing and loading), and chemical-resistant headgear (for 

overhead exposure). The proposed Akari®5SC label requires applicators and other handlers to 

wear a long-sleeved shirt and long pants, waterproof gloves, protective eyewear, and shoes plus 

socks. The label should be amended to specify the use of “chemical-resistant gloves” 

instead of “waterproof gloves.” RD should ensure the appropriate PPE is listed on the 

label.

Table 3.3.1. Summary of Proposed End-Use Product.

Trade Name EPA

Reg. No.

ai (% of 

formulation)

Formulation 

Type Target Crops Target Pests Label Date

Fujimite®5EC 

Miticide/

Insecticide

71711-19 5% (equivalent to 

0.4 lb ai/gal)

Emulsifiable

Concentrate

stone fruits (group 12-

12), small vine 

climbing fruits except 

kiwifruit (subgroup 

13-07F), and tuberous 

and corm vegetables 

(subgroup 1C)

Mites Undated 

draft label

Portal® Miticide/

Insecticide

Akari®5SC 

Miticide/

Insecticide

71711-4

5% (equivalent to 

0.42 lb ai/gal)

Soluble 

Concentrate

stone fruits (group 12-

12), and tuberous and 

corm vegetables 

(subgroup 1C)

Table 3.3.2. Summary of Directions for Use of Fenpyroximate.

Application 

Timing, Type, 

and 

Equipment

Formulation 

[EPA Reg. 

No.]

Maximum 

Application 

Rate (lb 

ai/A)

Maximum # 

Applications 

per Season

Max. 

Seasonal 

Application 

Rate (lb 

ai/A)

PHI1

(days)

Use Directions and 

Limitations

Small Fruit Vine Climbing (Except Fuzzy Kiwifruit) (Crop Subgroup 13-07F)

Airblast Fujimite® EC 

[71711-19] 0.05-0.1 2 0.1 14

RTI3= 14 days; Min. 

GPA2= 50; Do not apply 

by air; Do not apply 

through any type of 

irrigation system.

Tuberous and Corm Vegetables (Crop Subgroup 1C)

Groundboom, 

Aerial

Fujimite® 

EC/Portal®

[71711-19]

Akari® SC 

[71711-4]

0.1 2 0.2 7

RTI = 7 days; Min. GPA

= 20 (ground) and 5 (air); 

Do not apply through 

any type of irrigation 

system.

Stone Fruit (Crop Group 12-12)

Airblast

Fujimite®EC/ 

Portal® 

[71711-19]

Akari® SC 

[71711-4]

0.1 2 0.2 7

RTI = 14 days; Min. 

GPA = 80; Do not apply 

by air; Do not apply 

through any type of 

irrigation system.

1. PHI = pre-harvest interval.

2. GPA = gallons of water per acre.

3. RTI = retreatment interval.

The following rotational crop restriction appears on the proposed labels: “Do not plant rotational 

crops other than those listed on the label for 30 days following the last application of this 

product.” 
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3.4 Anticipated Exposure Pathways

RD has requested an assessment of human health risk to support the proposed new use of 

fenpyroximate on stone fruits (group 12-12), small vine climbing fruits except kiwifruit 

(subgroup 13-07F), and tuberous and corm vegetables (subgroup 1C). Humans may be exposed 

to fenpyroximate in food and drinking water, since it may be applied directly to growing crops, 

and application may result in fenpyroximate reaching surface and ground water sources of 

drinking water. As there are no residential uses of fenpyroximate, there is not likely to be 

exposure in residential or non-occupational settings. In an occupational setting, applicators may

be exposed while handling the pesticide prior to application, as well as during application. There 

is also potential for post-application exposure for workers re-entering treated fields. 

Risk assessments have been previously conducted for fenpyroximate, but no new toxicity data 

have been received since the previous risk assessment. This risk assessment considers all of the

aforementioned exposure pathways based on the proposed new uses of fenpyroximate, but also 

considers the existing uses as well, for the dietary and aggregate exposure assessments. 

3.5 Consideration of Environmental Justice

Potential areas of environmental justice concerns, to the extent possible, were considered in this 

human health risk assessment, in accordance with U.S. Executive Order 12898, "Federal Actions 

to Address Environmental Justice in Minority Populations and Low-Income Populations," 

(http://www.hss.energy.gov/nuclearsafety/env/guidance/justice/eo12898.pdf). As a part of every

pesticide risk assessment, OPP considers a large variety of consumer subgroups according to 

well-established procedures. In line with OPP policy, HED estimates risks to population 

subgroups from pesticide exposures that are based on patterns of that subgroup’s food and water 

consumption, and activities in and around the home that involve pesticide use in a residential 

setting. Extensive data on food consumption patterns are compiled by the USDA under the 

NHANES/WWEIA; 2003-2008 and are used in pesticide risk assessments for all registered food 

uses of a pesticide. These data are analyzed and categorized by subgroups based on age, season 

of the year, ethnic group, and region of the country. Additionally, OPP is able to assess dietary 

exposure to smaller, specialized subgroups and exposure assessments are performed when 

conditions or circumstances warrant. Whenever appropriate, non-dietary exposures based on 

home use of pesticide products and associated risks for adult applicators and for toddlers, youths, 

and adults entering or playing on treated areas post-application are evaluated. Further 

considerations are currently in development as OPP has committed resources and expertise to the 

development of specialized software and models that consider exposure to bystanders and farm 

workers as well as lifestyle and traditional dietary patterns among specific subgroups.

4.0 Hazard Characterization and Dose-Response Assessment

4.1 Hazard Profile

4.1.1 Mode of Action

Fenpyroximate is a contact insecticide/miticide used for the control of leafhoppers, mealybugs, 

and mites. The proposed pesticidal mode of action involves inhibition of mitochondrial function. 
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More specifically, fenpyroximate is a mitochondrial electron transport inhibitor that targets the 

enzyme NADH:ubiquinone oxidoreductase and blocks electron transfer to ubiquinone. 

4.2 Toxicology Studies Available for Analysis

The toxicological database for fenpyroximate is adequate for characterization of its hazard, 

toxicity endpoint selection, and FQPA SF consideration. In the last risk assessment (Memo, J. 

Tyler et al., 16-APR-2012, DP#391430), immunotoxicity and neurotoxicity studies (acute and 

subchronic) previously noted as data gaps were included in the hazard characterization along 

with a 4-week inhalation toxicity rat study previously submitted to the Agency.

4.2.1 Absorption, Distribution, Metabolism, & Elimination (ADME)

Following oral administration in the rat, radiolabeled fenpyroximate was slowly absorbed into 

the systemic circulation reaching maximum blood levels at 7-11 hours post dose. The 

elimination half-life in blood was estimated at 6.1-8.9 hours at the dose of 2 mg/kg bw. The 

liver contained up to 9.77% of the administered radioactivity after 6 hours, but decreased to 0.61-

0.78% at 12 hours. The majority of radioactivity was excreted in feces within the first 24 hours 

post-dosing. Feces accounted for 75.1-91.6% of the radioactivity, while the contribution of urine 

was 9.21-17.8%. The parent compound detected in feces accounted for only a small fraction 

(6.32-8.68%) of the administered dose. At least 20 different metabolites were characterized from 

excreta (urine and feces). The low levels of the parent chemical and the presence of different 

metabolites in feces is indicative of extensive absorption, metabolism, and biliary excretion. No 

sex-dependent differences were reported in ADME behavior.

4.2.1 Dermal Absorption

A dermal-absorption factor of 5% was previously estimated for fenpyroximate based on the 

results of a rat dermal penetration study. In addition, a route-specific dermal rat toxicity study

can be used to assess hazard associated with the dermal route of exposure.

4.3 Toxicological Effects

Fenpyroximate induced moderate acute lethality in rats (Category II) via the oral and inhalation 

routes of exposure. It exhibited low dermal acute toxicity (Category III) and was neither a skin 

nor eye irritant. Fenpyroximate was classified as a skin sensitizer by the maximization method, 

but not by the method of Buehler. HED considers fenpyroximate to be a slight to moderate 

sensitizer by the maximization test method. 

The effects following repeated oral exposures to fenpyroximate resulted in overall systemic 

toxicity (no specific target organ/tissue identified). The most sensitive species tested was the 

dog. The effects reported in subchronic and chronic studies in the dog included slight 

bradycardia, deficits in food consumption, body weight, body-weight gain, and an increased 

incidence of emesis and diarrhea. Emaciation and torpor (sluggish inactivity) were reported in 

female dogs at lower dose levels than males. The highest dose tested in the dog (50 mg/kg 

bw/day) resulted in first- and second-degree heart block, increased urea concentration, decreased 

glucose, and altered plasma electrolyte levels among other signs of toxicity. In subchronic and 
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chronic studies with rats, the primary effect was decreased body-weight gain in both sexes; there 

were hematological changes (e.g., higher counts of red blood cells) at higher doses. 

The rat and rabbit developmental toxicity studies were performed at dose levels that produced no 

or minimal maternal toxicity. In the rat study, a dose level that marginally affected maternal 

body weight and food consumption also resulted in an increased litter incidence of increased 

thoracic ribs, indicating increased prenatal (qualitative) susceptibility. In the rabbit prenatal 

developmental toxicity, there were no effects (maternal or developmental) reported at the levels 

tested. In the rat two-generation reproductive toxicity study, there was no indication of increased 

pre- or post-natal susceptibility; maternal toxicity (decreased body-weight) and offspring toxicity

(decreased lactational weight gain in both generations) occurred at the same dose. Reproductive 

parameters were not affected. 

There is no evidence that fenpyroximate specifically targets the nervous system based on the 

results of recently submitted acute and subchronic neurotoxicity studies in the rat. In the acute 

neurotoxicity study, neurotoxicity signs such as decreases in motor activity occurred in the 

presence of other effects including decreases in body weight and food consumption, and in the 

absence of neuropathology. Similar results were noted in a delayed acute neurotoxicity study in 

the hen where no effects (neurotoxic or otherwise) were reported at the limit dose (5000 mg/kg 

bw). The results of the rat subchronic neurotoxicity study did not indicate any neurotoxicityspecific effects; deficits in body weight and food consumption were the main effects reported.

In a recently submitted immunotoxicity study in rats, there were no immunotoxic effects reported 

at the dose levels tested. The treatment-related effects were limited to decreased body-weight 

gains in both sexes.

In a 21-day dermal toxicity study in rats, there were clinical signs in females consisting of red 

nose and mouth/nasal discharge, decreased body weights, body-weight gains, and food 

consumption in males and females. There were also increased liver weights and hepatocellular 

necrosis reported in females.

In a 4-week rat inhalation study, treatment-related effects included clinical observations (labored 

breathing and rales), increased lung weights, decreases in body-weight gain and food 

consumption, and changes in hematology parameters (increased counts of erythrocytes and 

leukocytes). There were also histopathology findings in the nasal passage mucosa consisting of 

atrophy and squamous metaplasia.

4.4 Safety Factor for Infants and Children (FQPA Safety Factor)

The RAB1 risk assessment team recommends that the FQPA SF be reduced to 1X for all 

exposure scenarios for the following reasons: the toxicological database is complete and 

adequate for FQPA consideration, there is no evidence of neurotoxicity, there was some 

evidence for qualitative susceptibility in the developing/young animals, however, there are no 

residual uncertainties for pre-and post-natal susceptibility for infants and children , and there is 

no uncertainty in the exposure database. The rationale is provided below.
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4.4.1 Completeness of the Toxicology Database

The existing toxicology database for fenpyroximate is complete and adequate for FQPA 

evaluation. There are acceptable developmental rat and rabbit toxicity studies, an acceptable rat 

two-generation reproduction study, and acceptable acute and subchronic neurotoxicity studies 

available for FQPA consideration.

4.4.2 Evidence of Neurotoxicity

There is no concern for neurotoxicity with fenpyroximate. Both acute and subchronic 

neurotoxicity studies in the rat did not indicate neurotoxicity-specific effects; reductions in body

weight and food consumption were the main effects reported. Further, both studies attained clear 

NOAELs.

4.4.3 Evidence of Sensitivity/Susceptibility in the Developing or Young Animal

There was evidence for increased (qualitative) prenatal susceptibility following oral exposures in 

the rat developmental toxicity study. However, the concern is low because (1) there was a clear 

NOAEL established for the developmental effect consisting of an increased incidence of 

additional thoracic ribs; (2) the rat developmental toxicity study was selected as the critical study

for the acute dietary endpoint of the population of concern: females 13-49 years old; and (3) 

there is no other indication of increased pre- or post-natal susceptibility in the database.

4.4.4 Residual Uncertainty in the Exposure Database

There are no residual uncertainties with respect to exposure data. The dietary food exposure 

assessment utilizes tolerance-level residues (established or recommended) and 100% CT for all 

proposed/established commodities. By using these assumptions, the acute and chronic 

exposures/risks will not be underestimated. The dietary drinking water assessment utilizes water 

concentration values generated by models and associated modeling parameters, which are 

designed to provide conservative, health-protective, high-end estimates of water concentrations 

that will not likely be exceeded. There are no registered or proposed residential uses.

4.5 Toxicity Endpoint and Point of Departure Selections

4.5.1 Dose-Response Assessment

Acute Dietary - Females Age 13-49 Years Old: The acute dietary endpoint is based on an 

increased incidence of additional thoracic ribs in the rat developmental toxicity study at the 

lowest-observed-adverse-effect level (LOAEL) of 25 mg/kg bw (NOAEL = 5 mg/kg bw). The 

developmental effects were reported in the presence of mild maternal toxicity (marginal decrease 

in body-weight gain and food consumption). The standard combined uncertainty factor (UF) of 

100X is being applied to account for interspecies (10X) and intraspecies (10X) extrapolation. 

The FQPA SF was not retained for this exposure scenario since the toxicology database is 

complete and there were no residual uncertainties for pre-and or post-natal susceptibility. Thus, 

the acute reference dose (aRfD) and aPAD are equivalent at 0.05 mg/kg bw.
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Acute Dietary - General U.S. Population: This acute dietary endpoint is based on the results of 

the acute neurotoxicity study. The effects at the LOAEL of 150 mg/kg bw (NOAEL=37.5 mg/kg 

bw) were based on decreased motor activity (total activity counts and total time spent in 

movement) in both sexes, and a reduction in auditory startle response in females at 24 hours post 

dose, and mild dehydration in males. The standard combined UF of 100X is being applied to 

account for interspecies (10X) and intraspecies (10X) extrapolation. The FQPA SF was not 

retained for this exposure scenario since the toxicology database is complete and there were no 

residual uncertainties for pre-and or post-natal susceptibility. Thus, the aRfD and aPAD are 

equivalent at 0.375 mg/kg bw.

Chronic Dietary - All Populations: A dog chronic toxicity study was selected for this exposure 

scenario since the dog is the most sensitive species. The LOAEL of 15 mg/kg bw/day (NOAEL 

= 5.0 mg/kg bw/day) was based on an increased incidence of bradycardia, diarrhea, and emesis 

and decreases in body-weight gain, food consumption, and cholesterol. The standard combined 

UF of 100X was applied to account for interspecies (10X) and intraspecies (10X) extrapolation. 

The FQPA SF was not retained for this exposure scenario since the toxicology database is 

complete and there were no residual uncertainties for pre-and or post-natal susceptibility. Thus, 

the chronic reference dose (cRfD) and cPAD are equivalent, estimated at 0.05 mg/kg bw.

Dermal Exposure (Short- and Intermediate-Term): This endpoint is based on the results of a rat 

21-day dermal toxicity study. The effects at the LOAEL of 1000 mg/kg bw/day (NOAEL = 300 

mg/kg bw/day) consisted of clinical signs in females, decreased body weights, body-weights 

gains, and food consumption in both sexes, increased absolute liver weights and a possible 

increase in hepatocellular necrosis in the females. An LOC of 100 which includes interspecies 

(10X) and intraspecies (10X) extrapolation is adequate for this scenario.

Inhalation Exposure (Short- and Intermediate-Term): This endpoint is based on the results of a 

rat 4-week inhalation toxicity study. The effects at the LOAEL of 10 mg/m3(NOAEL = 2 

mg/m3) consisted of increased lung weights, changes in hematology parameters (increased 

counts of erythrocytes), and histopathology findings in the nasal passage mucosa consisting of 

atrophy and squamous metaplasia.

The methods and dosimetry equations described in EPA’s reference concentration (RfC) 

guidance (1994) are suited for calculating HECs based on the inhalation toxicity NOAEL for use 

in MOE calculations. The regional-deposited-dose ratio (RDDR), which accounts for the 

particulate diameter (mass median aerodynamic diameter [MMAD] and geometric standard 

deviation [g] of aerosols), can be used to estimate the different dose fractions deposited along 

the respiratory tract. The RDDR is also based on interspecies differences in ventilation and 

respiratory-tract surface areas. Thus, the RDDR can be used to adjust an observed inhalation 

particulate exposure of an animal to the predicted inhalation exposure for a human. For the 4-

week inhalation study with fenpyroximate, an RDDR was estimated at 1.2 based on the reported 

MMAD of 3.00 μm and standard deviation (g) of 2.20 and the respiratory-tract surface area of 

the rat relative to the human (see Appendix for detailed calculations). Since the rat inhalation 

study was carried out for 6 hr/day for 5 days/week, the only exposure adjustment made was in 

the assumption of 8 hrs/day for human occupational exposures. The resulting HEC is 0.002 

mg/L. The LOC for this scenario is 30, which includes interspecies (3X) and intraspecies (10X) 
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extrapolation. The interspecies factor was reduced from 10X to 3X due to the HEC calculation 

accounting for pharmacokinetic (not pharmacodynamic) interspecies differences.

4.5.2 Recommendation for Combining Routes of Exposures for Risk Assessment

Exposures (dermal, oral, and inhalation) can be combined if the toxicological effects are the 

same. The dermal POD was selected from a 21-day dermal-toxicity study in rats in which 

clinical signs in females, decreased body weights, body-weights gains, and food consumption in 

both sexes, increased absolute liver weights and a possible increase in hepatocellular necrosis in 

the females were observed, The inhalation POD was selected from an inhalation toxicity study

in rats in which increased lung weights, changes in hematology parameters (increased counts of 

erythrocytes), and histopathology findings in the nasal passage mucosa consisting of atrophy and 

squamous metaplasia were observed. Therefore, for fenpyroximate, the dermal and inhalation 

routes cannot be combined for risk assessment since a common endpoint was not observed. 

4.5.3 Cancer Classification and Risk Assessment Recommendation

There is no evidence of carcinogenic potential for fenpyroximate based on the results of 

carcinogenicity studies via the oral route in either the rats or mice resulting in the carcinogenicity 

classification of “not likely” to be carcinogenic to humans.”

4.5.4 Summary of Points of Departure and Toxicity Endpoints Used in Human Risk 

Assessment

Table 4.5.4 summarizes the toxicological doses and endpoints selected for human-health risk 

assessment. 

Table 4.5.4. Summary of Toxicology Endpoints and PODs for Fenpyroximate in Dietary and Occupational Risk 

Assessment.

Exposure

Scenario POD

Uncertainty/ FQPA Safety 

Factors or LOC for Risk 

Assessment

Study and Toxicological Effects

Acute Dietary

(Females 13-49 years 

old)

NOAEL = 5.0

mg/kg bw

UF = 100X

(for inter- and intra-species 

extrapolation)

FQPA SF = 1X

aRfD = aPAD = 0.05 mg/kg bw

Prenatal Developmental Toxicity Study -

Rat

LOAEL = 25 mg/kg/day based on increase 

in the fetal incidence of additional thoracic 

ribs.

Acute Dietary

(General Population)

NOAEL = 37.5 

mg/kg bw

UF = 100X

(for inter- and intra-species 

extrapolation)

FQPA SF = 1X

aRfD = aPAD = 0.375 mg/kg bw

Acute Neurotoxicity Study - Rat

LOAEL = 150 mg/kg bw based on 

decreased motor activity (total activity 

counts and total time spent in movement) in 

both sexes, and a reduction in auditory 

startle response in females at 24 hours post 

dose, and mild dehydration in males.

Chronic Dietary

(All populations)

NOAEL = 5.0

mg/kg/day

UF = 100X

(for inter- and intra-species 

extrapolation)

FQPA SF = 1X

cRfD = cPAD = 0.05 mg/kg/day

Chronic toxicity - Dogs

LOAEL = 15 mg/kg/day based on an 

increased incidence of bradycardia, 

diarrhea, and decreases in cholesterol, bodyweight gain, and food consumption (M); 

vomiting, diarrhea, excess salivation and 
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Table 4.5.4. Summary of Toxicology Endpoints and PODs for Fenpyroximate in Dietary and Occupational Risk 

Assessment.

Exposure

Scenario POD

Uncertainty/ FQPA Safety 

Factors or LOC for Risk 

Assessment

Study and Toxicological Effects

decrease cholesterol in females.

Dermal

(Short- and 

Intermediate-Term)

NOAEL = 300

mg/kg bw/day

LOC = 100

(for inter- and intra-species 

extrapolation)

21-day Dermal toxicity study

LOAEL = 1000 (limit dose) based on 

clinical signs in the females, decreased body 

weights, body-weights gains, and food 

consumption in both sexes, increased 

absolute liver weights and a possible 

increase in hepatocellular necrosis in the 

females.

Short- and 

Intermediate-Term

Inhalation

Rat NOAEL = 

0.002 mg/L

LOC = 30

(3X interspecies,

10X intraspecies)

Inhalation toxicity study - Rat

LOAEL = 0.01 mg/L based on increased 

lung weights, changes in hematology 

parameters (increased counts of 

erythrocytes), and histopathology findings 

in the nasal passage mucosa consisting of 

atrophy and squamous metaplasia.

HEC = 0.002 mg/L

HED = 0.10 mg/kg 

bw/day

Cancer 

(Oral, dermal, 

inhalation)

Classification: “Not likely to be carcinogen,” cancer risk assessment is not required.

NOAEL = no-observed adverse-effect level, LOAEL = lowest-observed adverse-effect level, PAD = population-adjusted dose (a = acute, c = chronic), MOE = 

margin of exposure, HEC = human-equivalent concentration; HED = human-equivalent dose.

HEC = rat NOAEL*(daily duration adjustment)*weekly daily duration adjustment *RDDR*

 = 0.002 mg/L * (6hr/8hr)*(1)*1.2 = 0.0018 or 0.002 mg/L

HED = HEC*human-specific conversion factor*daily duration

 = 0.002 mg/L * 6.0 L/hr/kg*8hr = 0.096 or 0.10 mg/kg bw/day

5.0 Dietary Exposure and Risk Assessment 

The residue chemistry data submitted in support of the proposed petitions were evaluated by 

HED (Memo, G. Kramer, 08-MAY-2013, DP# 405715). The drinking water assessment was 

completed by EFED on 20-SEP-2012 (Memo, G. Orrick, DP# 404840). The dietary exposure 

assessment was completed in a HED memorandum (Memo, G. Kramer, 08-MAY-2013, DP# 

405718). 

5.1 Residues of Concern Summary and Rationale

The nature of the residue in crops is understood based on acceptable plant metabolism studies 

with fenpyroximate on snap beans, apples, citrus, cotton, and grapes. The HED Metabolism 

Assessment Review Committee (MARC) has determined that the residues of concern for 

purposes of tolerance enforcement and risk assessment are the parent compound plus its Zisomer (M-1) (Memo, J. Stokes, 12-JUL-2003; DP# 292639). The nature of the residue in 

ruminants is adequately understood based on an acceptable metabolism study in goats. The 

MARC reviewed these data and determined that the residues of concern for purposes of tolerance 

enforcement and risk assessment are parent, Fen-OH [(E)-1,1-dimethylethyl-2-hydroxyethyl 4-

[[[[(1,3-dimethyl-5-phenoxy-1H-pyrazol-4-yl)methylene]amino]oxy]methyl]benzoate], and M3 

[(E)-4-[(1,3-dimethyl-5-phenoxypyrazol-4-yl)-methylene aminooxymethyl]benzoic acid] in 
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milk, meat, and fat; and parent and M3 in liver and kidney. For drinking water, the residues of 

concern for risk assessment include the parent, M-1 and M-3.

5.2 Food Residue Profile

No new residue data were submitted to support the tolerance on small vine climbing fruits except 

kiwifruit (subgroup 13-07F). IR-4 has requested that the established tolerance for residues in/on 

grape be expanded to its respective crop group.

The submitted field trial residue data for stone fruit and potatoes are adequate. The field trial 

data reflect the proposed use pattern; an adequate number of trials were conducted in the 

appropriate geographic regions; and samples were analyzed for the residue of concern using 

validated data-collection methods. The storage intervals were also validated. Using the 

Organization for Economic Co-operation and Development (OECD) tolerance calculation 

procedures for the residue data sets indicate that the requested tolerance levels are appropriate. 

However, a revised Section F with corrected commodity definitions is requested (see Table 

2.2.2).

The submitted plum and potato processing studies are also adequate. Separate tolerances are not 

required for residues in/on any of the processed fractions.

No new livestock feeding studies were submitted with this petition. The only cattle feed 

commodities associated with this petition are potato culls and processed waste. The additional 

fenpyroximate uses are not expected to result in an increase in the maximum reasonably 

balanced diets (MRBDs). The existing tolerances on ruminant commodities are thus adequate to 

support registration of the proposed new uses of fenpyroximate. There are no swine or poultry

feedstuffs associated with this petition.

An adequate confined rotational crop study is available. [14C]-Fenpyroximate was applied to 

sandy loam soil at 0.20 lb ai/A (1X the maximum seasonal rate to annual crops addressed in this 

petition). Crops of radish, lettuce, and wheat were planted at 30, 120, and 365 days after 

treatment. Residues were too low to allow for metabolite identification. A field rotational crop 

study and rotational crop tolerances will, therefore, not be needed to support the proposed and 

registered uses. The proposed 30-day plant-back interval (PBI) is appropriate.

5.3 Water Residue Profile

Drinking water residues were incorporated directly into the acute and chronic dietary analyses 

(“water, direct, all sources” and “water, indirect, all sources”) and were provided by EFED . The 

EDWCs were screening-level estimates generated with the FIRST and a Provisional Cranberry

Model for fenpyroximate and its metabolites (M-1 and M-3) in surface water and with SCIGROW for ground water. Although the current and proposed end-use labels that result in the 

highest exposure are for ornamentals (an application rate to ornamentals of 0.343 lbs ai/A with a 

maximum application of 0.686 lbs ai/A), the use scenario with the highest acute and chronic 

EDWCs are for the cranberry scenario (see Table 5.3).
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Table 5.3. Maximum Screening EDWCs of Fenpyroximate for Current and Proposed Uses.1

Drinking Water Source (model) Use (Maximum Annual Rate)

EDWC (ppb)

Acute (peak 

exposure)

Chronic (annual 

mean exposure)

Surface Water (FIRST) Ornamentals (0.69 lb ai/A) 29 1.9

Surface Water (Cranberry model) Cranberries (0.20 lb ai/A) 43 8.6

Groundwater (SCI-GROW) Ornamentals (0.69 lb ai/A) <0.27

1. Maximum values in bold.

Surface water EDWCs of 43 ppm and 8.6 ppm were used in the acute and chronic analyses, 

respectively, as these values were the highest and provided a more conservative approach.

5.4 Dietary Risk Assessment

Acute and chronic aggregate dietary (food + drinking water) exposure and risk assessments were 

conducted for fenpyroximate using DEEM-FCID, ver. 3.16 which incorporates consumption data 

from USDA NHANES/WWEIA (2003-2008). A cancer dietary (food + drinking water) 

exposure and risk assessment was not performed because fenpyroximate is not carcinogenic.

5.4.1 Description of Residue Data Used in Dietary Assessment

The acute and chronic dietary exposure assessments were unrefined, using tolerance-level 

residues and assuming 100% CT for all registered and proposed commodities. Exposure to 

drinking water was incorporated directly in the acute and chronic dietary assessments using the 

acute (peak) and chronic (annual average) concentrations for surface water generated by the 

Provisional Cranberry Model, respectively.

5.4.2 Percent Crop Treated Used in Dietary Assessment

The acute and chronic dietary exposure assessments assumed 100% CT for all registered and 

proposed uses.

5.4.3 Acute Dietary Risk Assessment

Separate acute dietary exposure analyses were conducted for females 13-49 years old and for the 

general U.S. population as separate endpoints of concern attributable to a single dose were 

identified. Both acute analyses assumed 100% CT, tolerance-level residues for all commodities, 

DEEM (ver. 7.81) default processing factors for all commodities excluding apple, pear, and 

grape juice (0.11x); grape, raisin (2.7x); orange, grapefruit, tangerine, lemon and lime juice 

(0.06x); tomato paste (1.0x) and puree (1.0x); and peppermint and spearmint oil (0.08x). The 

acute analyses incorporated the EDWCs provided by EFED. An EDWC of 0.043 ppm was used 

in the acute analyses, as this was the highest (i.e., most conservative) estimate. 

The resulting acute food plus drinking water risk estimates are not of concern to HED (<100% of 

the aPAD) at the 95th percentile of the exposure distribution for females 13-49 years old or the 

general U.S. population. The resulting acute risk estimate is 13% of the aPAD at the 95th

percentile of the exposure distribution for females 13-49 years old. The highest acute exposure 
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estimate for the U.S. population or population subgroup is children 1-2 years old, which resulted 

in a risk estimate of 6.2% of the aPAD.

5.4.4 Chronic Dietary Risk Assessment

The chronic analysis assumed 100% CT, tolerance-level residues for all commodities, and 

DEEM (ver. 7.81) default processing factors for most commodities (see above). The chronic 

analysis also incorporated EDWCs provided by EFED (an EDWC of 0.0086 ppm was used in the 

chronic analysis).

The resulting chronic risk estimates are not of concern to HED (<100% of the cPAD). The most 

highly exposed population was children 1-2 years old with a risk estimate of 15% of the cPAD.

5.4.5 Summary Table

Table 5.4.5. Summary of Dietary (Food and Drinking Water) Exposure and Risk for Fenpyroximate.

Population Subgroup1

Acute Dietary (95th Percentile)2 Chronic Dietary3

Dietary Exposure 

(mg/kg/day) % aPAD Dietary Exposure(mg/kg/day) % cPAD

General U.S. Population 0.008312 2.2 0.002208 4.4

All Infants (<1 year old) 0.022585 6.0 0.004700 9.4

Children 1-2 years old 0.023191 6.2 0.007336 15

Children 3-5 years old 0.016596 4.4 0.005098 10

Children 6-12 years old 0.009835 2.6 0.002723 5.4

Youth 13-19 years old 0.005336 1.4 0.001394 2.8

Adults 20-49 years old 0.006565 1.8 0.001712 3.4

Adults 50-99 years old 0.006917 1.8 0.002013 4.0

Females 13-49 years old 0.006685 13 0.001693 3.4

1. The values for the highest exposed population for each type of risk assessment are bolded.

2. Separate acute toxicity endpoints were determined for females 13-49 years old and the general U.S. population and all population 

subgroups.

3. Chronic dietary endpoint of 0.05 mg/kg/day applies to the general U.S. population and all population subgroups. 

6.0 Residential (Non-Occupational) Exposure/Risk Characterization

The proposed use is on agricultural crops; therefore, a quantitative residential exposure 

assessment was not conducted. In addition, there are no proposed or existing fenpyroximate 

products registered for residential use sites.

6.1 Residential Bystander Post-Application Inhalation Exposure

Based on the Agency's current practices, a quantitative residential bystander post-application 

inhalation exposure assessment was not performed for fenpyroximate at this time primarily

because it has a low vapor pressure (5.6 x 10-8 mmHg), and it is applied at a low use rate (0.1 lb 

ai/A). However, volatilization of pesticides may be a potential source of post-application 

inhalation exposure to individuals nearby to pesticide applications. The Agency sought expert 

advice and input on issues related to volatilization of pesticides from its Federal Insecticide, 

Fungicide, and Rodenticide Act (FIFRA) Scientific Advisory Panel (SAP) in December 2009. 

The Agency received the SAP’s final report on March 2, 2010 
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(http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The Agency is in the 

process of evaluating the SAP report and may, as appropriate, develop policies and procedures, 

to identify the need for and, subsequently, the way to incorporate post-application inhalation 

exposure into the Agency's risk assessments. If new policies or procedures are put into place, the 

Agency may revisit the need for a quantitative post-application inhalation exposure assessment 

for fenpyroximate.

6.2 Spray Drift

Spray drift is always a potential source of exposure to residents nearby to spraying operations. 

This is particularly the case with aerial application, but, to a lesser extent, could also be a 

potential source of exposure from ground application. The Agency has been working with the 

Spray Drift Task Force, EPA Regional Offices, and State Lead Agencies for pesticide regulation 

and other parties to develop the best spray drift management practices. The Agency is now 

requiring interim mitigation measures for aerial applications that must be placed on product 

labels/labeling. The Agency has completed its evaluation of the new database submitted by the 

Spray Drift Task Force, a membership of U.S. pesticide registrants, and is developing a policy on 

how to appropriately apply the data and the AgDRIFT®computer model to its risk assessments 

for pesticides applied by air, orchard air-blast, and ground hydraulic methods. After the policy is 

in place, the Agency may impose further refinements in spray-drift-management practices to 

reduce off-target drift and risks associated with aerial as well as other application types where 

appropriate.

Although a quantitative residential post-application inhalation-exposure assessment was not 

performed as a result of pesticide drift from neighboring treated agricultural fields, an inhalationexposure assessment was performed for flaggers. This exposure scenario is representative of a 

worse case inhalation (drift) exposure and may be considered protective of most outdoor 

agricultural and commercial post-application inhalation exposure scenarios. 

7.0 Aggregate Exposure/Risk Characterization

The Agency conducts aggregate exposure assessments by summing dietary (food and water) and 

residential exposures (residential or other non-occupational exposures). Since there are no 

registered/proposed uses of fenpyroximate that result in residential exposure, the acute and 

chronic aggregate risk assessments are equal to the acute dietary and chronic dietary estimates 

(food and water only), respectively (see Table 5.4.5). Short-, intermediate-, and long-term 

aggregate-risk assessments were not performed because there are no registered or proposed uses 

of fenpyroximate that result in residential exposures. A cancer aggregate-risk assessment was 

not performed because fenpyroximate is not carcinogenic.

7.1 Acute Aggregate Risk

No acute residential/recreational exposures are expected. In the case of fenpyroximate, the acute 

aggregate risk is composed of exposures to fenpyroximate residues in food and drinking water 

and is equivalent to the acute dietary risk discussed in Section 5.4.5. The acute risk estimates do 

not exceed the HED’s LOC for the general U.S. population and all population subgroups.
Fenpyroximate Human-Health Risk Assessment DP No. 404839

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7.2 Chronic Aggregate Risk

A long-term aggregate risk assessment was not performed, because long-term residential 

exposure to fenpyroximate (i.e., >6 months) is unlikely to occur based upon the use patterns. 

Specifically, in the case of fenpyroximate, the chronic aggregate risk is composed of exposures 

to fenpyroximate residues in food and drinking water and is equivalent to the chronic dietary risk 

discussed in Section 5.4.5. The chronic risk estimates do not exceed the HED’s LOC for the 

general U.S. population and all population subgroups.

8.0 Cumulative Exposure/Risk Characterization

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a 

common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as 

to fenpyroximate and any other substances and fenpyroximate does not appear to produce a toxic 

metabolite produced by other substances. For the purposes of this tolerance action, therefore, 

EPA has not assumed that fenpyroximate has a common mechanism of toxicity with other 

substances. For information regarding EPA’s efforts to determine which chemicals have a 

common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the 

policy statements released by EPA’s Office of Pesticide Programs concerning common 

mechanism determinations and procedures for cumulating effects from substances found to have 

a common mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/.

9.0 Occupational Exposure/Risk Characterization

Based on the proposed application scenarios and toxicological considerations, non-cancer 

occupational handler (dermal and inhalation) and post-application (dermal) assessments were 

conducted for the proposed uses. The occupational exposure assessment was completed by J. 

Tyler (Memo, 08-MAY-2013, DP#404839), and reviewed by the Exposure Science Advisory 

Committee (ExpoSAC) on 21-FEB-2013.

9.1 Handler Exposure/Risk Estimates

HED uses the term handlers to describe those individuals who are involved in the pesticide 

application process. HED believes that there are distinct job functions or tasks related to 

applications and exposures can vary depending on the specifics of each task. Job requirements 

(amount of chemical used in each application), the kinds of equipment used, the target being 

treated, and the level of protection used by a handler can cause exposure levels to differ in a 

manner specific to each application event. 

Based on the anticipated use patterns and current labeling, types of equipment and techniques 

that can potentially be used, occupational handler exposure is expected from the proposed uses. 

The quantitative exposure/risk assessment developed for occupational handlers is based on the 

following scenarios:

Mixer/Loaders

 mixing/loading liquids in support of aerial applications,
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 mixing/loading liquids in support of groundboom applications,

 mixing/loading liquids in support of airblast applications,

Applicators

 applying with enclosed cockpit aerial equipment,

 applying with open-cab groundboom equipment

 applying with airblast equipment, and 

Flaggers

 flagging to support aerial applications. 

It is the policy of HED to use the best available data to assess handler exposure. Sources of 

generic handler data, used as surrogate data in the absence of chemical-specific data, include 

PHED 1.1, the AHETF database, the ORETF database, or other registrant-submitted 

occupational exposure studies. Some of these data are proprietary (e.g., AHETF data), and 

subject to the data protection provisions of FIFRA. The standard values recommended for use in 

predicting handler exposure that are used in this assessment, known as “unit exposures,” are 

outlined in the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table”

(http://www.epa.gov/opp00001/science/handler-exposure-table.pdf), which, along with 

additional information on HED policy on use of surrogate data, including descriptions of the 

various sources, can be found at the Agency website

(http://www.epa.gov/pesticides/science/handler-exposure-data.html). 

Estimates of dermal and inhalation exposure were calculated for various levels of PPE. Results 

are presented for “baseline,” defined as a single layer of clothing consisting of a long-sleeved 

shirt, long pants, shoes plus socks, no protective gloves, and no respirator, as well as baseline 

with various levels of PPE as necessary (e.g., gloves, respirator, etc). See Section 3.3 for a 

detailed description of the required PPE for proposed labels.

Handler exposure is expected to be short- and intermediate-term based on information provided 

on the label for the proposed uses (e.g., maximum of two spray applications per season at a 

maximum rate of 0.1 lb ai/A with 14 days between applications). Typically, HED completes 

short- and intermediate-term assessments for occupational scenarios in all cases because these 

kinds of exposures are likely, and acceptable use/usage data are not available to justify deleting 

intermediate-term scenarios. Based on use data and label instructions, HED believes that 

occupational exposures may occur over a single day or up to weeks at a time for many of the 

use-patterns and that intermittent exposure over several weeks may also occur. Some applicators 

may apply these products over a period of weeks, because they are commercial applicators who 

are completing multiple pesticide applications for multiple clients. Long-term exposures are not 

expected; therefore, a long-term assessment was not conducted.

The Agency matches quantitative occupational exposure assessment with appropriate 

characterization of exposure potential. While HED presents quantitative risk estimates for 

human flaggers where appropriate, agricultural aviation has changed dramatically over the past 

two decades. According to the 2012 National Agricultural Aviation Association (NAAA) survey

of their membership, the use of Global Positioning System (GPS) for swath guidance in 

agricultural aviation has grown steadily from the mid 1990s. Over the same time period, the use 

of human flaggers for aerial pesticide applications has decreased steadily from ~15% in the late 

1990s to only 1% in the most recent (2012) NAAA survey. The Agency will continue to monitor 
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all available information sources to best assess and characterize the exposure potential for human 

flaggers in agricultural aerial applications.

Table 9.1.1 provides a summary of the estimated exposures and risk estimates to occupational 

pesticide handlers. A MOE ≥ 100 is adequate to protect occupational pesticide handlers from 

dermal exposures, and a MOE ≥ 30 is adequate to protect occupational handlers from inhalation 

exposures. For the scenarios where baseline data are available, all dermal and inhalation risk

estimates for occupational handlers are above the LOC (MOE ≥ 100 for dermal and MOE ≥ 30 

for inhalation ) with baseline protection (i.e., long-sleeve shirt, long pants, shoes, and socks). 

Only engineering-control data (i.e., enclosed cockpits) are available for aerial application 

scenarios. All dermal and inhalation risk estimates for occupational aerial applicators are above 

the LOC (MOE ≥ 100 for dermal and MOE ≥ 30 for inhalation) with baseline clothing and 

enclosed cockpits.
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Table 9.1.1. Short- and Intermediate-Term Occupational Exposure and Risk Estimates for Fenpyroximate.

Exposure 

Scenario Crop or Target

Dermal Unit 

Exposure (ug/lb 

ai)1

Inhalation Unit 

Exposure (ug/lb ai)1 Maximum

Application 

Rate2

Area Treated 

or Amount 

Handled Daily3

Dermal Inhalation

Mitigation Level Mitigation Level Dose 

(mg/kg/day)4 MOE5 Dose (mg/kg/day)4 MOE5

Mixer/Loader

Liquids – Aerial 

Applications

Tuberous and Corm Vegetables

(Crop Group 1C) Baseline6

: 220 Baseline: 0.219 0.1 1200 0.33 910 0.000329 300

Liquids –

Groundboom 

Applications

Tuberous and Corm Vegetables

(Crop Group 1C) Baseline: 220 Baseline: 0.219 0.1 200 0.055 5500 0.0000548 1800

Liquids –

Airblast

Applications

Small Fruit Vine Climbing 

(Except Fuzzy Kiwifruit) (Crop 

Group 13-07F) Baseline: 220 Baseline: 0.219 0.1 40 0.011 27000 0.000011 9100

Stone Fruit (Crop Group 12-12)

Applicator

Aerial 

Applications

Tuberous and Corm Vegetables

(Crop Group 1C) Eng. Controls7

: 5 Eng. Controls: 0.068 0.1 1200 0.0075 40000 0.000102 980

Groundboom 

Applications

Tuberous and Corm Vegetables

(Crop Group 1C) Baseline: 78.6 Baseline: 0.34 0.1 200 0.0196 15000 0.000085 1200

Airblast

Small Fruit Vine Climbing 

(Except Fuzzy Kiwifruit) (Crop 

Group 13-07F) Baseline: 1770 Baseline: 4.71 0.1 40 0.0885 3400 0.000235 430

Stone Fruit (Crop Group 12-12)

Flagger

Flagger Tuberous and Corm Vegetables

(Crop Group 1C) Baseline: 11 Baseline: 0.35 0.1 350 0.00481 62000 0.000154 650

1. Unit Exposures are taken from “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table,” September 2012. 

2. Application Rate = 0.1 lb ai/A. Taken from proposed Fujimite® EC/Portal®[71711-19] and Akari® SC [71711-19] labels.

3. Units Treated are taken from “Standard Values for Daily Acres Treated in Agriculture”; ExpoSAC SOP No. 9.1, revised 25 September 2001.

4. Average Daily Dose = Unit Exposure (μg/lb ai) × Conversion Factor (0.001 mg/μg) × Application Rate (lb ai/acre) × Area Treated (A) ÷ BW (kg).

5. MOE = margin of exposure = NOAEL  ADD. NOAEL = 300 mg/kg bw/day (dermal), 0.10 mg/kg bw/day (inhalation).

6. Baseline = long-sleeve shirt, long pants, and no gloves (dermal); no respirator (inhalation).

7. Engineering Control = enclosed cockpit and baseline attire (long-sleeve shirt, long pants, shoes, and socks).
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9.2 Post-Application Exposure/Risk Estimates

HED uses the term post-application to describe exposures that occur when individuals are 

present in an environment that has been previously treated with a pesticide (also referred to as reentry exposure). Such exposures may occur when workers enter previously treated areas to 

perform job functions, including activities related to crop production, such as scouting for pests 

or harvesting. Post-application exposure levels vary over time and depend on such things as the 

type of activity, the nature of the crop or target that was treated, the type of pesticide application, 

and the chemical’s degradation properties. In addition, the timing of pesticide applications, 

relative to harvest activities, can greatly reduce the potential for post-application exposure.

9.2.1 Dermal Post-application Risk

HED expects that post-application exposure will occur since fenpyroximate is applied as a foliar 

spray. Post-application exposure is expected to be short-term based on information provided on 

the label (a maximum of two applications per crop cycle). However, the short- and intermediateterm toxicological endpoints are the same; therefore, the estimates of risk for short-term duration 

exposures are protective of those for intermediate-term duration exposures. 

It is the policy of HED to use the best available data to assess post-application exposure. 

Sources of generic post-application data, used as surrogate data in the absence of chemicalspecific data, are derived from ARTF exposure monitoring studies, and, as proprietary data, are 

subject to the data protection provisions of FIFRA. The standard values recommended for use in 

predicting post-application exposure that are used in this assessment, known as “transfer 

coefficients,” are presented in the “Science Advisory Council for Exposure (ExpoSAC) Policy

3” (http://www.epa.gov/pesticides/science/exposac_policy3.pdf), which, along with additional 

information about the ARTF data, can be found at http://www.epa.gov/pesticides/science/postapp-exposure-data.html.

A summary of the post-application MOEs and respective reentry intervals is provided in Table 

9.2.1. The short-term post-application assessments for sugarcane resulted in MOEs of 100 or 

greater on “day 0” (immediately after application) for all exposure activities, and are not of 

concern.

Table 9.2.1. Summary of Short- and Intermediate-term Occupational/Commercial Post-application Risk 

Estimates for Fenpyroximate.

Crop/Site Activities

Transfer 

Coefficient 

(cm2/hr)

DFR

(μg/cm2)

1

Dermal Dose 

(mg/kg/day)2 MOE3

Tuberous and Corm 

Vegetables

(Crop Group 1C)

Irrigation (hand set) 1,900 0.28 0.0532 5,600

Scouting 210 0.28 0.00588 5,100

Weeding, hand 70 0.28 0.00196 150,000

Small Fruit Vine 

Climbing (Except Fuzzy 

Kiwifruit) (Crop Group 

13-07F)

Girdling; Turning 19,300 0.28 0.54 560

Grapes (wine): Tying/training; 

Harvesting, hand; Leaf pulling 10,100 0.28 0.283 1,100

Grapes (table and raisin)

Tying/training; Harvesting, hand; Leaf 

pulling 

5,500 0.28 0.154 1,900

Irrigation (hand set) 1,900 0.28 0.0532 5,600
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Table 9.2.1. Summary of Short- and Intermediate-term Occupational/Commercial Post-application Risk 

Estimates for Fenpyroximate.

Crop/Site Activities

Transfer 

Coefficient 

(cm2/hr)

DFR

(μg/cm2)

1

Dermal Dose 

(mg/kg/day)2 MOE3

Scouting; Pruning, hand; Weeding, 

hand; Bird control; Trellis repair 640 0.28 0.0179 17,000

Stone Fruit (Crop 

Group 12-12)

Thinning fruit 3,600 0.8 0.101 3,000

Harvesting, hand 1,400 0.28 0.0392 7,700

Scouting; Pruning, hand; Training 580 0.28 0.0162 19,000

Weeding, hand; Orchard maintenance; 

Bird control; Propping 100 0.28 0.0028 110,000

1. DFR (μg/cm2) = Application Rate (lb ai/A) x (1-Daily Dissipation Rate)tx CF (4.54E+8 μg/lb) x CF (2.47E-8 A/cm2) x 25% DFR after 

initial treatment.

2. Daily Dose = [DFR (μg/cm2) x TC (cm2/hr) x 0.001 mg/μg x 8 hrs/day] ÷ Body Weight (80 kg).

3. MOE = NOAEL (Short- and Intermediate-term NOAEL 300 mg/kg/day)/Daily Dose (LOC=100).

REI: The proposed FujiMite®, Portal®, and Akari®labels list 12-hour REIs. Fenpyroximate is 

classified as Toxicity Category II for acute dermal toxicity and Toxicity Category IV for primary

eye irritation and primary dermal irritation. Therefore, while an assessment of systemic toxicity

from post-application exposure would indicate acceptable MOEs on the day of treatment, the 

acute toxicity categories for this chemical require a 24-hour REI for this product under the WPS. 

RD should ensure that all fenpyroximate labels have the appropriate REI listed.

Dislodgeable Foliar Residue (DFR): In accordance with the updated Part 158 data requirements 

(2007), one or more DFR studies are required when a pesticide has residential or occupational 

uses that could result in post-application dermal exposure. As part of the recent revision to the 

Health Effects Division’s 2012 Standard Operating Procedures for Residential Pesticide 

Exposure Assessment, HED analyzed a number of DFR studies and selected a new default value 

for the fraction of the application rate available to be dislodged after a foliar application (FAR). 

This default value is 25% and is based on an analysis of 19 DFR studies where the FAR value 

ranged from 2% to 89%. This value is recommended for use in both residential and occupational 

post-application assessments. Of the analyzed DFR studies, the maximum FAR value seen was 

89% or 3.6 times higher than the default residue transfer value. Therefore, the HED has decided 

that a calculated MOE of approximately 4 times higher than the LOC (e.g., an MOE > 400 if the 

LOC = 100) using the default dislodged residue values would provide an adequate margin of 

safety for any potentially higher residues seen in a chemical-specific DFR study (Guidance for 

Requiring/Waiving Turf Transferrable Residue (TTR) and DFR Studies. 6/7/2012, Exposure 

Science Advisory Council). A DFR study is not required for fenpyroximate at this time since the 

dermal MOEs are greater than 400 (i.e., 4x higher than the LOC) based on default values for the 

fraction of application rate available for transfer after a foliar application.

9.2.2 Inhalation Post-application Risk

Based on the Agency's current practices, a quantitative occupational post-application inhalation 

exposure assessment was not performed for fenpyroximate at this time primarily because it has a 

low vapor pressure (5.6 x 10-8 mmHg) and is applied at a low use rate (0.1 lb ai/A). However, 

there are multiple potential sources of post-application inhalation exposure to individuals 

performing post-application activities in previously treated areas. These potential sources 

include volatilization of pesticides and resuspension of dusts and/or particulates that contain 
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pesticides. The Agency sought expert advice and input on issues related to volatilization of 

pesticides from its FIFRA SAP in December 2009, and received the SAP’s final report on March 

2, 2010 (http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html). The Agency is 

in the process of evaluating the SAP report as well as available post-application inhalation 

exposure data generated by the Agricultural Reentry Task Force and may, as appropriate, 

develop policies and procedures, to identify the need for and, subsequently, the way to 

incorporate occupational post-application inhalation exposure into the Agency's risk 

assessments. If new policies or procedures are put into place, the Agency may revisit the need 

for a quantitative occupational post-application inhalation exposure assessment for 

fenpyroximate.

Although a quantitative occupational post-application inhalation exposure assessment was not 

performed, an inhalation exposure assessment was performed for occupational/commercial 

handlers. Handler exposure resulting from application of pesticides outdoors is likely to result in 

higher exposure than post-application exposure. Therefore, it is expected that these handler 

inhalation exposure estimates would be protective of most occupational post-application 

inhalation exposure scenarios.

10.0 References

G. Kramer, 08-MAY-2013, DP# 405715, Petition for the Establishment of Permanent Tolerances 

for Residues in/on Stone Fruits (Group 12-12), Tuberous and Corm Vegetables (Subgroup 1C), 

and Small Vine Climbing Fruits Except Kiwifruit (Subgroup 13-07F). Summary of Analytical 

Chemistry and Residue Data.

G. Kramer, 08-MAY-2013, DP# 405718, Petition for the Establishment of Permanent Tolerances 

for Residues in/on Stone Fruits (Group 12-12), Tuberous and Corm Vegetables (Subgroup 1C), 

and Small Vine Climbing Fruits Except Kiwifruit (Subgroup 13-07F). Acute and Chronic 

Dietary Exposure and Risk Assessments.

G. Orrick, 20-SEP-2012, DP# 404840, Drinking Water Exposure Assessment for Proposed New 

Uses on Stone Fruits (Crop Group 12-12), Tuberous and Corm Vegetables (Crop Subgroup 1C), 

and Small Vine Climbing Fruits Except Kiwifruit (Crop Subgroup 13-07F).

J. Stokes, 12-JUL-2003, DP# 292639, Conclusion and Briefing Memorandum for 07/09/03 

Meeting of the HED MARC.

J. Tyler et al., 16-APR-2012, DP# 391430, Human-Health Risk Assessment for 1) Proposed 

Section 3 Uses on Cucumber, Snap Bean, Avocado, Black Sapote, Canistel, Mamey Sapote, 

Mango, Papaya, Sapodilla, Star Apple, Corn (Field, Pop, Silage, and Grown for Seed); 2) 

Updated Tolerances for Citrus Fruit- Group 10-10, Pome Fruit Group 11-10, and Fruiting 

Vegetable Group 8-10; 4) the Establishment of a Tolerance on Imported Tea; 3) Increase I n 

Maximum Seasonal Application Rate on Mint; and 4) Proposed Label Amendment to Include 

Aerial Applications to Existing Uses on Citrus in Texas, Melons, Fruiting Vegetables, and Snap 

Beans.
Fenpyroximate Human-Health Risk Assessment DP No. 404839

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J. Tyler, 08-MAY-2013, DP# 404839, Occupational and Residential Exposure Assessment for a 

Proposed Use on Stone Fruit Group 12-12; Small Fruit Vine Climbing, Except Fuzzy Kiwifruit, 

Subgroup 13-07F; and Tuberous and Corm Subgroup 1C.

cc: J. Tyler (RAB1), G. Kramer (RAB1), C. Rodriquez (RAB1) 

RDI: Risk Assessment Team (2/27/13); RAB1 (2/27/13); G. Kramer (5/8/13); D. Vogel (5/8/13)

J. Tyler:S10943:PY-S:(703)305-5564:7509P:RAB1
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Appendix A. Toxicology Profile Tables.

Table A1. Toxicity Testing Requirements for Fenpyroximate.

Test

Technical

Required Satisfied

870.1100 Acute Oral Toxicity

870.1200 Acute Dermal Toxicity

870.1300 Acute Inhalation Toxicity

870.2400 Primary Eye Irritation

870.2500 Primary Dermal Irritation

870.2600 Dermal Sensitization

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.3100 Oral Subchronic (rodent)

870.3150 Oral Subchronic (nonrodent)

870.3200 21-Day Dermal

870.3250 90-Day Dermal

870.3465 28-Day Inhalation

yes

yes

yes

no

yes

yes

yes

yes

-

yes

870.3700a Developmental Toxicity (rodent)

870.3700b Developmental Toxicity (non-rodent)

870.3800 Reproduction

yes

yes

yes

yes

yes

yes

870.4100a Chronic Toxicity (rodent)

870.4100b Chronic Toxicity (non-rodent)

870.4200a Oncogenicity (rat)

870.4200b Oncogenicity (mouse)

870.4300 Chronic/Oncogenicity

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes

870.5100 Mutagenicity—Gene Mutation - bacterial

870.5300 Mutagenicity—Gene Mutation - mammalian

870.5400 Mutagenicity—Structural Chromosomal Aberrations

870.5500 Mutagenicity—Other Genotoxic Effects

yes

yes

yes

yes

yes

yes

yes

yes

870.6100a Acute Delayed Neurotox. (hen)

870.6100b 90-Day Neurotoxicity (hen)

870.6200a Acute Neurotox. Screening Battery (rat)

870.6200b 90-Day Neuro. Screening Battery (rat)

870.6300 Develop. Neurotoxicity

no

no

yes

yes

no

-

-

yes

yes

-

870.7485 General Metabolism

870.7600 Dermal Penetration

yes

yes

yes

yes

Special Studies for Ocular Effects

Acute Oral (rat)...........................................................

Subchronic Oral (rat) ..................................................

Six-month Oral (dog)..................................................

no

no

no

-

-

-
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Table A2. Acute Toxicity of Fenpyroximate.

Guideline No. Study Type MRID #s Results Toxicity 

Category

870.1100 Acute oral-rat 43560501

LD50 = 450 mg/kg males

LD50 = 245 mg/kg females

LD50 = 350 mg/kg combined

II

870.1200 Acute dermal-rat 44847901 LD50 >2,000 mg/kg III

870.1300 Acute inhalation-rat 44847902

LC50 = 0.24 mg/L (male)

LC50 = 0.37 mg/L (female)

LC50 = 0.35 mg/L (combined)

II

870.2400 Acute eye irritation-rabbit 44781004 Not an ocular irritant. IV

870.2500 Acute dermal irritationrabbit 44781005 Not a dermal irritant. IV

870.2600 Skin sensitization-guinea 

pig 44781006 Slight to moderate dermal sensitizer by the maximization test method. N/A

1. MRID 44781007 indicates that the technical is not dermal sensitizer by the Buehler method.

Table A3. Toxicity Profile for Fenpyroximate Technical.

Guideline No./ Study 

Type

MRID No. (year)/ Classification 

/Doses Results

870.3100

90-Day oral toxicity 

rodents (rats)

43429501 (1987)

Acceptable/guideline

0, 20, 100, or 500 ppm

M & F: 1.5, 7.4, or 37 mg/kg/day

NOAEL = 1.5 mg/kg/day (20 ppm).

LOAEL = 7.4 mg/kg/day (100 ppm) for rats, based on decreased 

body-weight gains in both sexes.

870.3150

90-Day dog oral toxicity 

(nonrodents)

43429502 (1988)

Acceptable/guideline

0, 2, 10, 50 mg/kg/day (capsule)

NOAEL <2 mg/kg/day.

LOAEL = 2 mg/kg/day, based on slight bradycardia and an 

increased incidence of diarrhea in both sexes; and reduced food 

consumption, body weight, body-weight gain, emaciation, and 

torpor in females. 

870.3200

21-Day dermal toxicity

(rats)

44781012 (1992)

Unacceptable/guideline

0 or 1000 mg/kg/day 

6 hr/day, 5 d/week

NOAEL <1000 mg/kg/day (HDT).

LOAEL = 1000 mg/kg/day (the limit dose and the only dose 

tested) based on decreased body-weight gains in males and 

females and increased liver weights in the females.

870.3200

21-Day dermal toxicity

(rats)

44781013 (1992)

Acceptable/guideline

0, 100, 300, or 1000 mg/kg/day

NOAEL = 300 mg/kg/day.

LOAEL = 1000 mg/kg/day (limit dose) based on clinical signs in 

the females, decreased body weights, body-weights gains, and 

food consumption in both sexes, increased absolute liver weights 

and a possible increase in hepatocellular necrosis in the females.

870.3465

28-Day inhalation toxicity

(rats)

45323302 (1991)

Acceptable/guideline

0, 2, 10, or 50 mg/m3

NOAEL = 2 mg/m3

LOAEL = 10 mg/m3based on treatment related effects with 

hematology (increased erythrocyte count), organ weights 

(increased lung weights) and microscopic pathology (squamous 

metaplasia of nasal passage mucosa).

870.3700a

Prenatal developmental 

toxicity (rats)

43429505 & 44519906 (1989)

Acceptable/guideline 

F: 0, 1, 5, or 25 mg/kg/day

Maternal NOAEL = 5 mg/kg/day.

LOAEL = 25 mg/kg/day based on marginal decrease in bodyweight gain and food consumption.

Developmental NOAEL = 5 mg/kg/day.

LOAEL = 25 mg/kg/day based on increased incidence of 

additional thoracic ribs.

870.3700b

Prenatal developmental 

toxicity (rabbits)

43429504, 44519903 - 44519905 

(1989)

Acceptable/guideline; however, 

the study cannot be used for 

establishing RfD. 

F: 0, 1, 2.5, or 5 mg/kg/day

Maternal NOAEL = 5 mg/kg/day.

LOAEL >5.

Developmental NOAEL = 5 mg/kg/day.

LOAEL >5 mg/kg/day.

870.3800

Reproduction and fertility 

effects (rats)

43429506 (1989)

Acceptable/guideline

0, 10, 30, or 100 ppm

F0(M/F): 0/0, 0.67/0.83, 2.0/2.4, 

or 6.6/8.6 mg/kg/day

Parental/Systemic NOAEL = 1.99 mg/kg/day for males 2.44 

mg/kg/day for and females.

LOAEL = 6.59 and 8.60 mg/kg/day for males and females, 

respectively, based on decreased body-weights during the 

premating period.
Fenpyroximate Human-Health Risk Assessment DP No. 404839

Page 32 of 34

Table A3. Toxicity Profile for Fenpyroximate Technical.

Guideline No./ Study 

Type

MRID No. (year)/ Classification 

/Doses Results

F1(M/F): 0/0, 0.78/0.96, 2.3/2.8, 

or 8.4/9.9 mg/kg/day

Reproductive NOAEL = 6.59 and 8.60 mg/kg/day for males and 

females, respectively.

LOAEL was not established.

Offspring NOAEL = 2.44 mg/kg/day.

LOAEL = 8.60 mg/kg/day, based on decreased lactational 

weight gain in both generations of pups.

870.4100a

Chronic toxicity (rodents)

NA; see 870.4300 NA

870.4100b

Chronic toxicity (dogs)

43429503 (1989)

Acceptable/guideline

0, 0.5, 1.5, 5, or 15 mg/kg/day 

(capsule)

NOAEL = 5 mg/kg/day. 

LOAEL = 15 mg/kg/day in both sexes, based on diarrhea, 

bradycardia, and decrease cholesterol, body-weight gain, and 

food consumption (M); vomiting, diarrhea, excess salivation, and 

decrease cholesterol in females.

870.4200a

Carcinogenicity (rats)

NA; see 870.4300 NA

870.4200b

Carcinogenicity (mice)

43560503 (1989)

Acceptable/guideline

0, 25, 100, 400, or 800 ppm

M: 0, 2.4, 9.5, 38, or 69.6 

mg/kg/day

F: 0, 2.5, 10, 41.5, or 73 

mg/kg/day

NOAEL = Males: 2.4 mg/kg/day; Females: 2.5 mg/kg/day.

LOAEL = Males: 9.5 mg/kg/day; Females: 10 mg/kg/day based 

on decreased body weights, and food consumption.

No evidence of carcinogenicity.

870.4300

Combined 

Chronic/carcinogenicity 

(rats)

43560502 (1989)

Acceptable/guideline

0, 10, 25, 75, or 150 ppm

M: 0, 0.4, 0.97, 3.0, or 6.2 

mg/kg/day

F: 0, 0.49, 1.21, 3.81, or 6.18 

mg/kg/day

NOAEL = Males: 0.97 mg/kg/day; Females: 1.16 mg/kg/day.

LOAEL = Males: 3.08 mg/kg/day; Females: 3.79 mg/kg/day 

based on decreased mean body-weight gain.

No evidence of carcinogenicity.

870.5100

Bacterial reverse mutation

43429507 (1989)

Acceptable/guideline

S. typhimurium strains and 

Escherichia coli WP2uvrA were 

exposed to NNI-850 technical 

(97.3% ai) in DMSO at 50, 158, 

500, 1580, and 5000 μg/plate ± S9 

metabolic activation. 

At limit concentration (5000 μg/plate) inhibition of growth was 

observed in strains TA98, TA1537, TA1538 and WP2uvrA. The 

positive controls induced the appropriate responses in the 

corresponding strains. There was no evidence of induced 

mutant colonies over background.

870.5300

In vitro mammalian cell 

gene mutation

43429508 (1988)

Acceptable/guideline

Chinese hamster V79 cells were 

exposed at concentrations of 3, 10, 

30, 100, and 330 μg/ml ± S9 

activation.

Not cytotoxic up to 330 μg/ml, the limit of solubility. There 

was no evidence of mutagenic effect at any dose level with or 

without metabolic activation. The positive controls induced 

the appropriate response.

870.5375

In vitro mammalian 

chromosome aberration 

(HL)

43429509 (1989)

Acceptable/guideline

The preliminary test was 

conducted at 3-330 μg/ml with and 

without S-9 activation. In the 

main study, human lymphocytes 

were exposed at 1.25-20 μg/ml ± 

S9 activation.

Tested up to limit of solubility (up to 330 μg/ml). For metaphase 

analysis, the highest concentration (20 μg/ml) produced 

moderate toxicity (mitotic index ~57% of solvent control). Two 

lower concentrations produces mitotic indices 25% and 12.5% of 

the high concentration. Positive controls induced the appropriate 

response. The results of this study provide sufficient evidence 

to consider NNI-850 negative in this assay. 

870.5395

Mammalian micronucleus 

(mouse)

43429510 (1989)

Acceptable/guideline

Male and female CD-1 mice 

received a single dose of 80-2000 

mg/kg. 

There was suggestive evidence that NNI-850 was cytotoxic to 

the target cell at the highest dose level. The positive control 

induced significant increases in micronucleated polychromatic 

erythrocytes (MPCEs). There was no significant increase in 

the frequency of MPCEs in bone marrow after any NNI-850 

treatment time. Fenpyroximate is considered negative in this 

micronucleus assay. 

870.5500 43429511 (1988) Did not cause any inhibitory zone in either strain at any dose 
Fenpyroximate Human-Health Risk Assessment DP No. 404839

Page 33 of 34

Table A3. Toxicity Profile for Fenpyroximate Technical.

Guideline No./ Study 

Type

MRID No. (year)/ Classification 

/Doses Results

DNA damage/repair REC

assay

Acceptable/guideline

Cultures were exposed at 10-500 

μg/disk ± S9 activation. 

level in the presence or absence of metabolic activation. The 

negative and positive controls induced the appropriate responses.

870.5550

Unscheduled DNA 

synthesis (RPH)

43429512 (1989)

Acceptable/guideline

Primary rat hepatocyte cultures 

were exposed at 0.025-1.02 

μg/mL.

Fenpyroximate was negative. The positive control induced the 

appropriate response.

870.6100

Acute delayed 

neurotoxicity - hen

44847904 (1989)

Acceptable/guideline

5000 mg/kg/day (Limit Test)

NOAEL  5000 mg/kg/day. 

LOAEL was not observed.

870.6200

Acute Neurotoxicity

- Rat

48441401 (2011)

0, 37.5, 75, 150, 300 mg/kg bw

Acceptable/guideline

NOAEL = 150 mg/kg bw. 

LOAEL = 300 mg/kg bw based on decreased motor activity 

[total activity counts (males ↓46%; females ↓38%); total time 

spent in movement (↓54%; females ↓49%)].

870.6200

Subchronic neurotoxicity

- Rat 

48537704 (2011)

0, 30, 100, or 300 ppm 

M: 0, 1.8, 6.1, 16.4 mg/kg/day

F: 0, 2.0, 6.6, 18.4 mg/kg/day

Acceptable/guideline

NOAEL = 1.8 mg/kg bw/day.

LOAEL = 6.1 mg/kg bw/day based on deficits in body weight 

and food consumption.

870.7485

Metabolism and 

pharmacokinetics

rat

43560504 and 43560505 (1991)

43429513 (1990)

Acceptable/guideline

In a metabolism study, doses 

ranged from 2-400 mg/kg. In a 

separate blood pharmacokinetics 

study (MRID 43429513), five

rats/sex/dose were given single 

oral doses of [pyrazole14C] or 

[benzyl14C] fenpyroximate at 2 or 

400 mg/kg.

The majority of the radioactivity from the single and repeated 

low doses was excreted in the feces within 24 hours of dosing. 

In contrast, fecal excretion of the majority of the high dose was 

delayed until 96-144 hours; and, at 24 hours, the major portion 

of the single high dose (53.4-63.9%) remained in the stomach 

contents. The maximum concentration in blood (tmax) was 

reached at 7-11 hours following a single low dose compared with 

29-101 hours after a single high dose. The low doses were 

eliminated from blood within 96 hours, whereas the high dose 

persisted through 168 hours. 

A total of 20 metabolites, each accounting for <10% of the dose, 

were characterized from excreta (urine and feces) of low-dose 

rats. 

The preponderance of metabolites and low levels of parent in the 

feces at the 2 mg/kg dose indicates absorption from the digestive 

tract, extensive metabolism by the liver, and biliary excretion of 

the low dose (2 mg/kg). The high dose of 400 mg/kg causes as a 

toxic effect delayed excretion and decreased absorption and 

metabolism.

870.7600

Dermal penetration – Rat

45734204 (1993)

Acceptable/guideline

Test material was applied to a 10 

cm2area at nominal dose levels of 

10, 100 and 520 ug/cm2(actual 

10.6, 103 and 52.3 ug/cm2). 

Exposure durations were 0.5, 1, 2, 

4, 10 or 24 hours.

Mean absorption based on urinary/fecal excretion, blood, 

carcass, and cage wash ranged from 0 to 5.3% (0.0 to 5.3% low 

dose, 0.5 to 2.5% mid dose and 0.52 to 1.5% high dose).

Dermal-absorption factor is 5%.

870.7800

Immunotoxicity

48441402 (2011)

Acceptable/guideline

M: 0, 2.2, 7.1, 18.4 mg/kg/day

F: 0, 2.6, 7.9, 21.4 mg/kg/day

Immunotoxicity

NOAEL = 18.4 mg/kg bw/day (highest dose tested).

LOAEL = not identified.

Systemic toxicity

NOAEL = 2.2 mg/kg bw.

LOAEL = 7.1 mg/kg bw based on dose-related reduction in body 

weight in both sexes (21.3% decrease). 
Fenpyroximate Human-Health Risk Assessment DP No. 404839

Page 34 of 34

Appendix B. Physical/Chemical Properties

Table B1. Physicochemical Properties of Fenpyroximate.

Parameter Value Reference

Melting range 99.3-101.7 °C D301316, 5/3/04, L. Kutney

pH 5.63-6.10 D301316, 5/3/04, L. Kutney

Density 1.247-1.257 g/mL at 20 °C D301316, 5/3/04, L. Kutney

Water solubility Water, pH 5-21.4 ppb

Water, pH 7-23.1 ppb 

Water, pH 9-29.8 ppb

D257640, 8/20/99, G. Kramer

Solvent solubility Acetone 15.0 g/100 mL

Chloroform 119.7 g/100 mL

DMSO 2.86 g/100 mL

Ethanol 1.65 g/100 mL

Ethyl acetate 20.1 g/100 mL

Hexane 0.35 g/100 mL

Methanol 1.53 g/100 mL

Methylene chloride 130.7 g/100 mL

Tetrahydrofuran 73.7 g/100 mL

Toluene 26.8 g/100 mL

Xylene 19.3 g/100 mL

D301316, 5/3/04, L. Kutney

Vapor pressure 5.6 x 10-8 Pa at 25 °C D257640, 8/20/99, G. Kramer

Dissociation constant, pKa Not applicable; nearly insoluble in water D301316, 5/3/04, L. Kutney

Octanol/water partition coefficient, Log(KOW) log Pow = 5.01 (PAI) D301316, 5/3/04, L. Kutney